yabo亚洲 //www.tennisbs.com Train yourself to thrive on stress Sun, 20 Oct 2019 23:20:17 +0000 en-US hourly 1 https://wordpress.org/?v=5.4.1 12311508 Retraining the limbic brain to overcome obesity and addiction //www.tennisbs.com/2019/10/retraining-the-limbic-brain-to-overcome-obesity-and-addiction/ //www.tennisbs.com/2019/10/retraining-the-limbic-brain-to-overcome-obesity-and-addiction/#comments Todd Sun, 20 Oct 2019 01:58:21 +0000 Uncategorized //www.tennisbs.com/?p=25230 I presented this talk at the Ancestral Health Symposium in San Diego on August 10, 2019. It’s all about the brain processes that drive addiction and obesity — and how can we rewire those processes to regain control. Click image to view on YouTube: Here is a slide-by-slide synopsis of the talk. Retraining the limbic […] <p>I presented this talk at the Ancestral Health Symposium in San Diego on August 10, 2019. It’s all about the brain processes that drive addiction and obesity — and how can we rewire those processes to regain control.</p> <p>Click image to view on YouTube:</p> <figure class="wp-block-image is-resized"><a href="https://www.youtube.com/watch?v=yu8jrTvnQoI&t=2002s"><img src="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2019/10/Screen-Shot-2019-10-13-at-7.30.53-PM-e1571612809710.png?resize=572%2C301" alt="" class="wp-image-25231" width="572" height="301" data-recalc-dims="1" /></a></figure> <p>Here is a slide-by-slide synopsis of the talk.</p> <p><strong>Retraining the limbic brain to overcome obesity and addiction</strong></p> <ol><li>I have spoken at AHS in prior years on the principles of hormesis (beneficial low dose stress), the limitations of nutritional supplements, myopia reduction, and the benefits of living of high altitude.</li><li>Are the epidemics of obesity and addition an inevitable results of tastier food, strong drugs and other supernormal stimuli?</li><li>More than a third of Americans are clinically obese. Drug addiction, particularly to opioids, has reached epidemic proportions.</li><li>Addictions are directed towards not just substances, like food and chemicals, but also activities and technologies like gambling, shopping, pornography, the internet, smartphones, and social media.</li><li>Obesity and addition are multifactorial, including genetics and many environmental variables. I’ll focus in this talk on one causal factor common to both: cravings, which can defeat even the best-planned diets or recovery treatments.</li><li>One prevalent idea is that addiction and obesity result from supernormal stimuli — intense cues for food, sex and sociality that hijack our brains.</li><li>But can foods and drugs literally hijack our brains? Stimuli are not <em>inherently</em> addictive, but only become so through learning processes.</li><li>One approach to overcoming addiction is abstinence and 12-step programs. But even data from Alcoholics Anonymous indicates that less than 1/3 of its members remain sober for more than 10 years; independent studies show a lower success rate. </li><li>Can we just eat less palatable food, as Stephan Guyenet suggests? That might help, but it’s an unappealing approach with its own limitations.</li><li>Addiction expert and Bryn Mawr psychology professor expert Maya Szalavitz, herelf a former addict, provides support for conceptualizing addiction as a learning disorder.</li><li>The brain processes for addiction are coded in the paleomammailian brain — the limbic system and reward circuits of the basal ganglia.</li><li>Addiction is the result of two separate processes: a general process of hedonic reversal, resulting from receptor down-regulation in the hypothalamus; and reinforcement of highly specific addictive responses rooted in classical conditioning. These are coded in the amygdala and reward circuits of the limbic system.</li><li>The best account of the general propensity for addiction is the Opponent-Process theory of Solomon and Corbit, which explains how addiction results from the pursuit of pleasure, and at the same time how stressful or thrilling experiences lead to sustained euphoria.</li><li>The Opponent-Process theory originated in observations of the euphoria produced by skydiving, which becomes progressively more sustained with repeated jumps.</li><li>The model can be generalized to explain the opposite situation: the progressive despair and addiction resulting from adaptation to repeated pursuits of intense pleasures like drugs, gambling or sex.</li><li>These opponent processes are the brain’s way to maintain homeostasis of bodily functions and drives like body temperature, appetite and mood — all governed by the hypothalamus.</li><li>Judith Grisel, another addiction expert and former addict herself, describes how different drug classes activate different opponent processes associated with specific neurotransmitters. Stimulants activate “wanting” and dopamine receptors, where the opponent processes produce “craving”; Opioids and depressants activate “liking” and opioid receptors, where the opponent processes produce irritability. and even physical pain.</li><li>The Incentive Salience model of Berridge and Robinson shows how these opponent processes lead to progressively dysfunctional cycles of anticipation, bingeing, and withdrawal.</li><li>Koob and Volkow argue that when multiple cycles of these opponent processes exceed homeostatic tolerance thresholds, the pleasure set points are reset to progressively lower hedonic states. This process is called “allostasis”. As this allostatic process deepens, addicts pursue their addiction not even to feel good, but merely for relief from despair.</li><li>I’ve put forward a physiological hypothesis to explain the psychological Opponent Process theory, which I call the Receptor Control Theory. In essence, our pleasure set point or baseline “happiness” is determined by the density and sensitivity of dopamine receptors in the brain (and elsewhere). In this view, obesity and addiction result from a process of “dopamine resistance”, whereby receptor down-regulation impairs satisfaction and drives cravings. Conversely, high receptor density and sensitivity promote satisfaction and dampen cravings.</li><li>This theory finds support in PET scans from Nora Volkow showing reduced dopamine receptor density in the brains of addicted and obese human subjects. </li><li>And Whitten has shown that dopamine receptor density declines progressively with continued use of cocaine. </li><li>Dopamine reward cycles are associated not just with substance use, but also with reinforced activities like extensive smart phone usage. </li><li>Here’s the good news: PET brain scans in rats and humans demonstrate how receptor down-regulation caused by obesity and addiction can be reversed by hormesis — exposure to psychologically demanding activities like calorie restriction and exercise. </li><li>Now to the specific processes involved in addition: these are shaped by classical or Pavlovian conditioning, stimulus-response behavior coded by the amygdala and reward circuitry.</li><li>Skinner described operant conditioning of voluntary behaviors.</li><li>Pavlov described classical conditioning of involuntary physiological responses. His famous studies showed how dogs can learn to salivate as a “conditioned” response to an unfamiliar cue like a bell, that becomes associated with repetitive feeding of a natural or “unconditioned” cue like meat. Our hunger craving response to the aroma and sight of a pastry is a familiar example of classical conditioning.</li><li>Just as our general drives for food, sex and sleep are governed by the hypothalamus, our conditioned response to specific foods, sexual partners and sleep cues are coded in the amygdala.</li><li>The amygdala and hippocampus govern our “gut reactions”.</li><li>The dopamine and opioid reward circuitry that reinforce the cycles of wanting and liking described by Berridge and Robinson are coded in the basal ganglia.</li><li>There are also specific timing cues. The hormone ghrelin that governs appetite cues associated with meal timing and frequency can be conditioned, e.g. via yabo亚洲 .</li><li>We can usefully apply this understanding of classical conditioning to stop unwanted responses to cues by using 4 strategies: (1) stimulus avoidance; (2) cue exposure & extinction; (3) counter-conditioning; and (4) putting on cue.</li><li>Most people don’t realize that in his 1927 study of dogs, Pavlov showed how even their supposedly unconditioned “innate” salivation response to the presentation of meat could be extinguished or by repeatedly presenting the meat without allowing the dog to eat it. </li><li>Cue exposure therapy retrains responses to addictive cues by systematic exposure to cues without allowing the response.</li><li>Conklin and Tiffany reviewed 18 trials of cue exposure therapy to treat addictions, finding that the successful studies incorporated four factors: (1) varied context; (2) repeated presentation spaced in time; (3) presentation of the stimulus without normal cues; (4) extinguishing of behavioral cues, not just sensory cues.</li><li>A specific example of reconditioning is separating flavor cues from food reward. The Shangri-La 亚搏体育客户端下载 , devised by Seth Roberts, is an effective example of this, using flavorless calories or calorie-less flavors to deconditioning food cues. </li><li>Extinction and counterconditioning are very effective ways to decondition cravings, for example, for food, alcohol or smartphones.</li><li>I’ve developed the Deconditioning 亚搏体育客户端下载 as a specific protocol for overcoming food cravings. It has three phases: (1) a low-insulinogenic diet, cutting out snacks; (2) deconditioning using extinction and counterconditioning. Don’t eat when you’re hungry! Expose yourself to food aromas without eating!; and (3) yabo亚洲 to support long term dietary goals. </li><li>We can frame this in a more general 3-phase approach to fight cravings and addictions: (1) First increase your resilience and general hedonic state using psychological hormesis — engaging in strenuous or challenging physical activities; (2) Decondition specific cravings using extinction, cue exposure and counter-conditioning; and (3) Rebalance pleasure in your life, based on a goal of either reducing or eliminating an “addictive” pleasure. Reinforce problematic cues with alternative pleasures.</li><li>At the end of the video, I’ve provided references and blog posts on this site for on further reading.</li><li>In summary, addiction is complex, but a central challenge is overcoming cravings. Supernormal stimuli aren’t inherently addictive but become that way through conditioning. We can work our way out of addictions through a combination of hormesis (to improve resilience and baseline pleasure) and deconditioning of specific cravings using cue exposure and counterconditioning.</li></ol> <p>In the Q&A session, I fielded questions on several topics, including motivational barriers, complementary methods such as mindfulness, cognitive-behavioral therapy (CBT), “positive” addictions to exercise, hedonic challenges with ketogenic diets, positive reinforcement vs. punishment in banishing cravings, intermittent reinforcement and clicker training.</p> <p>If this talk interested you, here are links to related posts on this blog:</p> <ul><li><a href="//www.tennisbs.com/2010/05/opponent-process-theory/">T<strong>he opponent process theory of emotion</strong></a></li><li><a href="//www.tennisbs.com/2010/10/change-your-setpoint/"><strong>Change your receptors, change your set point</strong></a></li><li><a href="//www.tennisbs.com/2012/01/hormesis-and-the-limbic-brain/"><strong>yabo亚洲 and the limbic brain</strong></a></li><li><a href="//www.tennisbs.com/2010/04/overcoming-addictions/"><strong>Overcoming addiction</strong></a></li><li><a href="//www.tennisbs.com/2011/11/obesity-starts-in-the-brain-2/"><strong>Obesity starts in the brain</strong></a></li><li><a href="//www.tennisbs.com/2010/11/learning-to-fast/"><strong>Learning to fast</strong></a></li></ul> <p></p> //www.tennisbs.com/2019/10/retraining-the-limbic-brain-to-overcome-obesity-and-addiction/feed/ 2 25230 I’ll be talking at AHS19 in San Diego on August 10 //www.tennisbs.com/2019/07/ill-be-talking-at-ahs19-in-san-diego-on-august-8/ //www.tennisbs.com/2019/07/ill-be-talking-at-ahs19-in-san-diego-on-august-8/#respond Todd Sun, 28 Jul 2019 19:48:38 +0000 Uncategorized //www.tennisbs.com/?p=25208 I realize this blog has been pretty quiet, but that’s about to change. I’ll be presenting at the Ancestral Health Symposium at UC San Diego on August 10, 1:30-2:10 pm. It’s not too late to register. The conference runs from Thursday, August 8 to Saturday, August 10. It’s not too late to register – here’s […] <p>I realize this blog has been pretty quiet, but that’s about to change. I’ll be presenting at the Ancestral Health Symposium at UC San Diego on August 10, 1:30-2:10 pm. </p> <figure class="wp-block-image is-resized"><img src="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2019/07/Unknown-2.jpeg?resize=502%2C334&ssl=1" alt="" class="wp-image-25218" width="502" height="334" srcset="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2019/07/Unknown-2.jpeg?w=275&ssl=1 275w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2019/07/Unknown-2.jpeg?resize=150%2C100&ssl=1 150w" sizes="(max-width: 502px) 100vw, 502px" data-recalc-dims="1" /></figure> <p>It’s not too late to register. The conference runs from Thursday, August 8 to Saturday, August 10. <br><br>It’s not too late to register – here’s the link to the AHS website: <br><br><a href="http://www.ancestralhealth.org">AHS19 Conference in San Diego – Program Details</a></p> <p>Here is the title and abstract of my talk:</p> <p><strong> “Retraining the Limbic Brain to Overcome Obesity and Addictions”</strong></p> <p>This talk considers whether food and other stimuli are inherently addictive, or only become that way through conditioning. Insufficient attention has been paid to the role of the amygdala and learning processes in mediating the sensory, emotional and social inputs that can modulate hypothalamic drives for better or worse. I will outline ways that appetite and other drives can be usefully retrained, often with surprising effectiveness for losing weight and overcoming addictions.</p> <p>Modern maladies such as obesity and addiction have neural correlates in two ancients parts of the brain: the hypothalamus and the amygdala. Research has elucidated the particular neuronal structures and pathways that underlie the development of these conditions. Some have argued that the epidemics of obesity and addiction have their roots in the contemporary environment of hyperpalatable food and other supernormal addictive stimuli that hijack and dysregulate homeostatic control by the hypothalamus. </p> <p>Hope to see you there!</p> //www.tennisbs.com/2019/07/ill-be-talking-at-ahs19-in-san-diego-on-august-8/feed/ 0 25208 AHS 2018 videos: “yabo亚洲 ” and other talks //www.tennisbs.com/2018/10/ahs-2018-videos-hormesis-and-other-talks/ //www.tennisbs.com/2018/10/ahs-2018-videos-hormesis-and-other-talks/#respond Todd Tue, 16 Oct 2018 01:42:51 +0000 Uncategorized //www.tennisbs.com/?p=25189 Montana State University has now completed producing and editing the talks from this year’s Ancestral Health Symposium in Bozeman, Montana.  My previous post from July 19 is a static upload of the slides and summary point but if you are like me, you will probably find watching the video more understandable and enjoyable. Here is […] <p>Montana State University has now completed producing and editing the talks from this year’s Ancestral Health Symposium in Bozeman, Montana.  My previous post from July 19 is a static upload of the slides and summary point but if you are like me, you will probably find watching the video more understandable and enjoyable.</p> <p>Here is my talk on “How yabo亚洲 Works”:</p> <p> </p> <p><iframe src="https://www.youtube.com/embed/NDm_guQfESA" width="560" height="315" frameborder="0" allowfullscreen="allowfullscreen"></iframe></p> <p> </p> <p>And here is a link to the YouTube site with all the other talks from this summer’s conference.  There are some excellent ones here!</p> <p><a href="https://www.youtube.com/playlist?list=PLbhWKPDKXIEBL2LhXnRVzb3sjAkSbFece"><img class="size-full wp-image-25194 alignleft" src="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2018/10/AHS18-talks.jpg?resize=600%2C348&ssl=1" alt="" width="600" height="348" srcset="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2018/10/AHS18-talks.jpg?w=600&ssl=1 600w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2018/10/AHS18-talks.jpg?resize=150%2C87&ssl=1 150w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2018/10/AHS18-talks.jpg?resize=300%2C174&ssl=1 300w" sizes="(max-width: 600px) 100vw, 600px" data-recalc-dims="1" /></a></p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p> </p> <p>I’d welcome comments and feedback on any of these talks.</p> <p>Enjoy!</p> //www.tennisbs.com/2018/10/ahs-2018-videos-hormesis-and-other-talks/feed/ 0 25189 How yabo亚洲 Works //www.tennisbs.com/2018/07/how-hormesis-works/ //www.tennisbs.com/2018/07/how-hormesis-works/#respond Todd Thu, 19 Jul 2018 23:09:49 +0000 Uncategorized //www.tennisbs.com/?p=25164 I had the pleasure of delivering a presentation on this topic today at the Ancestral Health Symposium, in beautiful Bozeman, Montana.  This is my fourth such talk at AHS, a non-profit educational organization which brings together a collection of academics, practitioners, bloggers and others interested in evolutionary mismatch and its implications for health and well-being. […] <p>I had the pleasure of delivering a presentation on this topic today at the Ancestral Health Symposium, in beautiful Bozeman, Montana.  This is my fourth such talk at AHS, a non-profit educational organization which brings together a collection of academics, practitioners, bloggers and others interested in evolutionary mismatch and its implications for health and well-being.</p> <p>I’m posting the slides from my talk here – click on the image to see a pdf.  I’ll upload the full video once it becomes available in a few weeks.</p> <p> </p> <p><a href="//www.tennisbs.com/wp-content/uploads/2018/07/AHS18-How-yabo亚洲 -Works-7-19-18-final-1.pdf"><img class="alignright wp-image-25170 size-full" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2018/07/How-yabo亚洲 -Works.jpg?resize=620%2C470&ssl=1" alt="" width="620" height="470" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2018/07/How-yabo亚洲 -Works.jpg?w=779&ssl=1 779w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2018/07/How-yabo亚洲 -Works.jpg?resize=150%2C114&ssl=1 150w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2018/07/How-yabo亚洲 -Works.jpg?resize=300%2C227&ssl=1 300w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2018/07/How-yabo亚洲 -Works.jpg?resize=768%2C582&ssl=1 768w" sizes="(max-width: 620px) 100vw, 620px" data-recalc-dims="1" /></a></p> <p> </p> <p> </p> <p>This talk is about the biological mechanisms that explain hormesis – the beneficial  adaptation  to  intermittent, low dose stress.  Here is a synopsis of the talk, slide by slide:</p> <ol> <li>Title: How yabo亚洲 Works: The Biology of Beneficial Adaptation to Stress</li> <li>The yabo亚洲 blog has many specific examples of hormesis.  I have spoken at AHS on 3 prior occasions on different topics, but this will be a deeper dive into the mechanisms that underlie all types of hormesis.</li> <li>We are faced with pandemics of metabolic disease and psychological disorders.  Do these result from too much stress, or perhaps too little beneficial stress?</li> <li>yabo亚洲 is defined as the beneficial response  of an organism to a low dose stressor that is otherwise detrimental or lethal at higher doses.</li> <li>A survey of 9000 toxicology dose response curves in microbes, plants and animals show that 19.5% of them display evidence of a positive or stimulatory effect at lower doses.  The hormetic concentrations vary considerably for different chemicals, stressors and organisms.</li> <li>Why does hormesis exist?  Organisms must be able to adapt to changing, stressful environments or face extinction.</li> <li>Ancient man was a hunter gatherer, often facing food shortages, lack of shelter and infection.  Our modern evolutionary mismatch may be the fact that we are too comfortable and protected from the hormetic stimuli in our natural environment.</li> <li>But how does hormesis actually work?  What are the underlying biological mechanisms?</li> <li>I propose a “Hormetic Hierachy” of four main types of hormesis.  Starting at the foundation and moving higher, these types are: structural, defense, metabolic and psychological.</li> <li><strong>STRUCTURAL HORMESIS</strong> is the strengthening or adaptation of structural tissues in response to mechanical stimuli such as pressure, friction or stretching.</li> <li>Resistance  exercise for muscle growth is the classic example of structural hormesis.  Straining causes micro-trauma, release of growth factors that cause satellite cells to fuse into existing muscle and increase size and strength.</li> <li>This results in supercompensation.  Immediately after training, there is a decrease in strength or fitness.  After rest and recocvery, the resulting strength or fitness exceeds baseline.</li> <li>Bone is also strengthened by exercise  that  involves loading. This stimulates integrin proteins in the osteocyles to release FAK, leading osteoblasts to migrate, secrete collagen, and mineralize.</li> <li>Callus forms on skin in response to friction that stimulates the crosslinking of protein and keratinocytes by transglutaminase.</li> <li>Myopia is also a result of structural changes in the eye.</li> <li>Excessive reading or screen time induces pseudomyopia (spasm in the lens) resulting in blurry distance vision .  Getting minus lenses for distance correction temporarily solves the problem, but the eye is induced to elongate, cause, spurring a repeated need for stronger lenses.</li> <li>The lengthening of the eye axis results when repeated cycles of retinal defocus slow the release of neuromodulators that control proteoglycan synthesis in the sclera.  This weakens the scleral tissue integrity, increasing the eye’s axial length. Hyperopia is the opposite process.</li> <li>This explanation is supported by research in animals and humans showing how minus lenses begin lengthening the eye, while plus lenses shorten. This process starts in less than an  hour after wearing these lenses.  Repeating cycles consolidates the change.</li> <li>Myopia can thus be reversed by wearing plus lenses and print pushing while reading or at computers, and using progressively weaker minus lenses for distance viewing.</li> <li><strong>DEFENSE HORMESIS</strong> is the strengthening of immune  and xenobiotic defenses against foreign substances  and organisms, by appropriate exposures.</li> <li>The dramatic rise of allergy and autoimmune disease may be associated with the loss of our “ancestral microbiome” — a set of commensal organisms that co-evolved with us to stimulate regulatory T-cells which  moderate our B and T immunes cells not to over-react.</li> <li>The book “An Epidemic of Absence” by Velasquez-Manoff details numerous examples of allergies and  autoimmune  diseases controlled by exposure to microbes at specific life stages, including asthma, celiac, multiple sclerosis and autism.</li> <li>Xenobiotic metabolism is our defense against chemical toxins, including the natural plant toxins that we call “phytonutrients”.  The Nrf2 transcription factor mediates the production of endogenous Phase II antioxidant enzymes that neutralize oxidative stress from toxins as well as exercise.  Ironically, taking oral antioxidants suppresses Nrf2 and counteracts exercise benefits.</li> <li><strong>METABOLIC HORMESIS</strong> is the improved capacity and flexibility to utilize dietary or stored energy.</li> <li>yabo亚洲 activates a powerful “stress sensor” called PGC-1α, that triggers wide-ranging metabolic changes, starting with mitochondrial biogenesis.  PGC-1α is triggered by stressors such as cold exposure, exercise,, calorie restriction and hypoxia.  A train of hormonal and enzymatic changes bring about appetite suppression, exercise urge, insulin sensitivity and autophagy.</li> <li>PGC-1α inhibits mTOR activity, the master regulator of protein synthesis and growth processes.  While important in childhood and adolescent development, mTOR is associated with metabolic diseases of aging.  PGC-1α induces the protein REDD-1 that inhibits mTOR.</li> <li>PGC-1α also spurs autophagy, a cellular housecleaning process that digests damaged intracellular proteins and other byproducts.</li> <li>Autophagy promotes longevity by reducing inflammation, apoptosis, senescence and oncogenesis.  It stimulates the innate immune response  and removes intracellular pathogens.</li> <li>A popular theory of why we age is that we accrue progressive oxidative damage, impairing cellular function.</li> <li>The long-lived naked mole rat is a counterexample to the accumulated damage theory.  It is wracked with extensive oxidative damage in the skin and organs, yet lives 30 years compared to 3 years for laboratory mice.  It protects against the results of this damage via endogenous antioxidant enzymes.</li> <li>PGC-1α upregulates BDNF, which induces neurogenesis in the brain and improves insulin sensitivity in the muscles.</li> <li>The PGC-1α cascade also induces exercise salience — the urge to exercise.</li> <li>In the virtuous circle of hormesis, PGC-1α turns on mitochondrial biogenesis, improving energy flow, increasing the urge to exercise and suppressing appetite and inflammation.  This leads us to be more resilience and willing to expose ourselves to further hormetic stressors.</li> <li>In  the viscious cycle of inflammation, a sedentary lifestyle, caloric excess and inflammatory foods suppress mitochondrial biogenesis, lowering energy level and increasing the urge to eat while suppressing the desire to exercise.</li> <li>Keto-adaptation is another example of metabolic hormesis.  While it takes only a few days of fasting to induce ketosis, true keto-adaptation takes several weeks.  A great reference for these metabolic changes is  Phinny and Volek’s “The Art and Science of Low Carbohydrate Performance”, and their website www.artandscienceoflowcarb.com.</li> <li><strong>PSYCHOLOGICAL HORMESIS</strong> is increased resilience in the face of discomfort, by voluntary exposure to challenges.</li> <li>The opponent-process theory of emotion was developed to explain hedonic reversal: how, with time, pleasures become increasingly addictive, while certain uncomfortable challenges become tolerated and even lead to sustained pleasure after the event.</li> <li>The classic example studied by Solomon and Corbit was skydivers.  While the first jump provokes terror and some satisfaction after the jump is complete, after many jumps the initial fear experience is diminished, while the post-jump experience becomes euphoric and sustained.</li> <li>This phenomenon is explained by an inhibitory or opponent “B” process that counteracts the intensity of either the pleasure or pain of the intense “A” process. The B process becomes stronger with repetition, dampening the initial intensity of A and sustaining and deepening the intensity of B.</li> <li>These compensating opponent processes are not “mere psychology”, they are matched by underlying neurological changes. One example is the down-regulation of D2 dopamine receptors, imaged in PET brain scans, as seen in a study of smokers, alcoholics, cocaine users and the obese.</li> <li>Dopamine receptors are significantly down-regulated in cocaine over 6-12 months, deepening addictive cravings.</li> <li>Conversely, dopamine receptors can be upregulated hormetically.  Lean rats start with higher receptor density than obese rats, but both show dramatic D2 receptor activity increase after 4 months of caloric restriction.  Similar trends are seen in methamphetamine users who exercise while abstaining.</li> <li>SSRI anti-depressants exhibit tolerance associated with down-regulation of serotonin receptors.  But exercise has been show to have a lasting anti-depressant effect.</li> <li>I propose a “receptor control theory”, in which individuals have “pleasure set points” determined by the  number and sensitivity of different types of receptors.  Hormetic activities can increase receptor density, and thereby improve well-being and resilience to stress.</li> <li><strong>GENERAL PRINCIPLES</strong> of hormesis at all 4 levels include: plasticity, specificity,  supercompensation, secondary adaptation, and intermittency.</li> <li>Secondary adaptation involving lasting changes typically takes weeks or months to consolidate.</li> <li>Stress oscillation is important.  Hormetic stress exposure should alternate with periods of rest to enable consolidation and avoid chronic stress and burnout.</li> <li>In summary, hormetic challenge at all levels can bring about increased performance, health and resilience. Try out some hormetic activities like yabo亚洲 , cold showers, rock climbing or sky diving!</li> </ol> <p>Slide 49-52 provide supporting references.</p> <p>I’d also recommend scanning through past articles posted on this blog for more detail on specific examples of hormesis.</p> <p> </p> <p> </p> //www.tennisbs.com/2018/07/how-hormesis-works/feed/ 0 25164 A quick overview of Hormetism //www.tennisbs.com/2016/12/a-quick-overview-of-hormetism/ //www.tennisbs.com/2016/12/a-quick-overview-of-hormetism/#comments Todd Fri, 23 Dec 2016 20:23:57 +0000 Uncategorized //www.tennisbs.com/?p=5470 A recently did a podcast interview with Christopher Kelley, author of the website Nourish Balance Thrive.   Chris is a competitive cyclist who got interested in health and biohacking.  His site provides information and interviews to help athletes (and non-athletes) optimize their health and performance.  His generally Paleo approach combines testing, supplementation and lifestyle changes.  NBT also has a team […] <p><a href="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/12/Screen-Shot-2016-12-23-at-12.05.01-PM.png"><img class="alignright wp-image-5472" src="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/12/Screen-Shot-2016-12-23-at-12.05.01-PM.png?resize=270%2C217" alt="" width="270" height="217" srcset="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/12/Screen-Shot-2016-12-23-at-12.05.01-PM.png?w=430&ssl=1 430w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/12/Screen-Shot-2016-12-23-at-12.05.01-PM.png?resize=150%2C120&ssl=1 150w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/12/Screen-Shot-2016-12-23-at-12.05.01-PM.png?resize=300%2C241&ssl=1 300w" sizes="(max-width: 270px) 100vw, 270px" data-recalc-dims="1" /></a>A recently did a podcast interview with Christopher Kelley, author of the website <strong><a href="http://www.nourishbalancethrive.com/">Nourish Balance Thrive</a></strong>.   Chris is a competitive cyclist who got interested in health and biohacking.  His site provides information and interviews to help athletes (and non-athletes) optimize their health and performance.  His generally Paleo approach combines testing, supplementation and lifestyle changes.  NBT also has a team that provides personal consultation.</p> <p>I got to know Chris from discussions at several Ancestral Health Symposium meetings, and this led to the podcast interview.</p> <p>I’m putting up the interview here on my main page because Chris somehow managed to get me to weave together a broad range of topics in a conversational way,  succinctly and concretely illustrating the essence of hormesis and its application to improving health and well-being — what I call “Hormetism”.</p> <p>I’m also including here his minute-by-minute outline of the topics covered so you can jump in or out on at points that might interest you, and you can also follow up by clicking some of the links.  Enjoy!</p> <p style="padding-left: 30px;"><strong><span style="color: #993300;"><a style="color: #993300;" href="http://www.nourishbalancethrive.com/podcasts/nourish-balance-thrive/getting-stronger/">Chris Kelley Interviews Todd</a><br /> </span></strong></p> <h4 dir="ltr"></h4> <h4 dir="ltr">Outline of the podcast:</h4> <p dir="ltr" style="padding-left: 30px;">[00:00:24] <a href="https://youtu.be/x5Efg42-Qn0">Myopia: A Modern Yet Reversible Disease</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:00:53] <a href="https://youtu.be/Cii0JtiXBS4">AHS16 – Todd Becker – Living High and Healthy</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:01:48] <a href="https://en.wikipedia.org/wiki/yabo亚洲 ">yabo亚洲 </a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:02:35] Low-carb and yabo亚洲 .</p> <p dir="ltr" style="padding-left: 30px;">[00:03:58] Going on holiday and forgetting glasses.</p> <p dir="ltr" style="padding-left: 30px;">[00:04:40] <a href="//www.tennisbs.com/tag/print-pushing/">Print pushing</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:05:02] Exercise.</p> <p dir="ltr" style="padding-left: 30px;">[00:05:29] Immune system.</p> <p dir="ltr" style="padding-left: 30px;">[00:06:07] UV.</p> <p dir="ltr" style="padding-left: 30px;">[00:06:13] Overcompensation.</p> <p dir="ltr" style="padding-left: 30px;">[00:07:28] Lactose tolerance.</p> <p dir="ltr" style="padding-left: 30px;">[00:08:35] Unnecessarily avoiding the sun.</p> <p dir="ltr" style="padding-left: 30px;">[00:10:05] Finding the perfect amount of stress.</p> <p dir="ltr" style="padding-left: 30px;">[00:12:15] <a href="//www.tennisbs.com/2010/11/learning-to-fast/">Learning to fast blog post</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:13:00] <a href="http://www.nourishbalancethrive.com/podcasts/nourish-balance-thrive/jason-moore-elitehrv/">Heart rate variability</a> or even just resting HR.</p> <p dir="ltr" style="padding-left: 30px;">[00:14:02] Cold showers.</p> <p dir="ltr" style="padding-left: 30px;">[00:14:43] Alcohol.</p> <p dir="ltr" style="padding-left: 30px;">[00:15:53] Metabolic flexibility.</p> <p dir="ltr" style="padding-left: 30px;">[00:16:08] <a href="https://en.wikipedia.org/wiki/Allostasis">Allostasis</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:17:07] Wood smoke.</p> <p dir="ltr" style="padding-left: 30px;">[00:17:25] Evolutionary mismatches.</p> <p dir="ltr" style="padding-left: 30px;">[00:17:41] <a href="//www.tennisbs.com/2015/09/is-charred-meat-bad-for-you/">Is charred meat bad for you?</a></p> <p dir="ltr" style="padding-left: 30px;">[00:18:29] <a href="http://amzn.to/2gGhduH">Catching Fire: How Cooking Made Us Human</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:19:02] <a href="https://en.wikipedia.org/wiki/Drug_metabolism#Phases_of_detoxification">Phases of detoxification</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:19:17] <a href="https://en.wikipedia.org/wiki/CYP3A4">CYP3A4</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:19:42] <a href="https://en.wikipedia.org/wiki/Superoxide_dismutase">Superoxide dismutase</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:20:01] <a href="https://youtu.be/zz4YVJ4aRfg">Sulforaphane and Its Effects on Cancer, Mortality, Aging, Brain and Behavior, Heart Disease & More</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:21:28] <a href="//www.tennisbs.com/hormesis/">Low-dose dioxins</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:21:53] Hormone analogues.</p> <p dir="ltr" style="padding-left: 30px;">[00:22:14] Gluten.</p> <p dir="ltr" style="padding-left: 30px;">[00:22:40] IgE emergency response.</p> <p dir="ltr" style="padding-left: 30px;">[00:22:50] <a href="http://amzn.to/2gQbZ33">An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:23:36] Peanut allergies</p> <p dir="ltr" style="padding-left: 30px;">[00:23:56] <a href="https://en.wikipedia.org/wiki/Karelia_(historical_province_of_Finland)">Karelia</a> (historical province of Finland).</p> <p dir="ltr" style="padding-left: 30px;">[00:25:00] Reversing peanut allergies.</p> <p dir="ltr" style="padding-left: 30px;">[00:25:22] Poison ivy and oak.</p> <p dir="ltr" style="padding-left: 30px;">[00:26:49] Peanut oil in diaper cream.</p> <p dir="ltr" style="padding-left: 30px;">[00:27:06] Oral vs topical exposure.</p> <p dir="ltr" style="padding-left: 30px;">[00:27:23] <a href="https://en.wikipedia.org/wiki/Epstein%E2%80%93Barr_virus">Epstein–Barr virus</a> infection at certain ages.</p> <p dir="ltr" style="padding-left: 30px;">[00:28:09] Altitude.</p> <p dir="ltr" style="padding-left: 30px;">[00:28:24] Boulder has the lowest obesity rate in the US.</p> <p dir="ltr" style="padding-left: 30px;">[00:29:28] <a href="https://en.wikipedia.org/wiki/PPARGC1A">PGC1-a</a> via hypoxia.</p> <p dir="ltr" style="padding-left: 30px;">[00:30:16] <a href="http://www.nourishbalancethrive.com/podcasts/nourish-balance-thrive/pro-tour-rider-nutrition-and-benefits-fasted-state/">Barry Murray on my podcast</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:31:36] Altitude masks.</p> <p dir="ltr" style="padding-left: 30px;">[00:32:02] Train high race low.</p> <p dir="ltr" style="padding-left: 30px;">[00:32:24] <a href="http://www.nourishbalancethrive.com/podcasts/nourish-balance-thrive/national-cyclocross-champion-jeremy-powers-racing-/">Jeremy Powers on this podcast</a>.</p> <p dir="ltr" style="padding-left: 30px;">[00:34:43] <a href="//www.tennisbs.com/">www.tennisbs.com</a></p> <p dir="ltr">Happy listening.</p> //www.tennisbs.com/2016/12/a-quick-overview-of-hormetism/feed/ 2 5470 The health benefits of hypoxia and living at high altitude //www.tennisbs.com/2016/08/the-health-benefits-of-hypoxia/ //www.tennisbs.com/2016/08/the-health-benefits-of-hypoxia/#comments Todd Mon, 22 Aug 2016 03:25:42 +0000 Uncategorized aging Alistair Nunn altitude BDNF calorie restriction cardiovascular disease cold exposure diabetes exercise exercise salience FNDC5 yabo亚洲 hyperfunction hypoxia inflammation insulin yabo亚洲 irisin leptin longevity mitochondria obesity PGC-1a //www.tennisbs.com/?p=5400 I had the pleasure of attending and presenting at the Ancestral Health Symposium, in Boulder Colorado, August 11-13. My podium presentation was entitled “Living High and Healthy: Why Coloradans and Others Who Live at High Altitude Live Longer, and What Flatlanders Can Learn From Them”.   On several visits to Boulder and the Rocky Mountains, I was […] <p>I had the pleasure of attending and presenting at the Ancestral Health Symposium, in Boulder Colorado, August 11-13. My podium presentation was entitled “Living High and Healthy: Why Coloradans and Others Who Live at High Altitude Live Longer, and What Flatlanders Can Learn From Them”.   On several visits to Boulder and the Rocky Mountains, I was surprised that I had lost about 5-10 pounds after returning home to California. Subsequently, I was intrigued to learn that Boulder has the lowest obesity rate in the U.S., and that alpine regions around the world are distinguished by statistically lower prevalence of  obesity and diabetes, and also increased longevity.</p> <p>My curiosity about this issue spurred a deeper investigation, resulting in this  talk at AHS16. From the scientific literature, I learned that there is a specific hormetic mechanism involving hypoxia (reduced oxygen levels) that probably accounts for the health-promoting effects of living at high altitude.  However, it was particularly exciting to discover that hypoxia is not the only means of activating this hormetic mechanism, which can still be accessed even if you live at sea level!</p> <p>The Ancestry Foundation is kind enough to produce excellent videos of the talks and release them for free viewing on YouTube.  Enjoy watching!</p> <p> </p> <p><iframe class='youtube-player' type='text/html' width='620' height='349' src='https://www.youtube.com/embed/Cii0JtiXBS4?version=3&rel=1&fs=1&autohide=2&showsearch=0&showinfo=1&iv_load_policy=1&wmode=transparent' allowfullscreen='true' style='border:0;'></iframe></p> <p><span id="more-5400"></span></p> <p>To make the talk easier to digest, I’ve also reproduced my slides here, with a short written synopsis and references:</p> <p><span style="text-decoration: underline;"><strong>Slides: </strong></span></p> <p style="text-align: center;">(Click on image below and allow 30-60 seconds for slide show to upload)</p> <p style="text-align: center;"><a href="//www.tennisbs.com/wp-content/uploads/2016/08/AHS16-Becker-Living-High-and-Healthy-8-12-16-blog-version.pdf" target="_blank"><img class="aligncenter wp-image-5410 size-large" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2016/08/Screen-Shot-2016-08-18-at-8.49.10-PM.jpg?resize=620%2C464" width="620" height="464" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2016/08/Screen-Shot-2016-08-18-at-8.49.10-PM.jpg?resize=1024%2C766&ssl=1 1024w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2016/08/Screen-Shot-2016-08-18-at-8.49.10-PM.jpg?resize=150%2C112&ssl=1 150w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2016/08/Screen-Shot-2016-08-18-at-8.49.10-PM.jpg?resize=300%2C224&ssl=1 300w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2016/08/Screen-Shot-2016-08-18-at-8.49.10-PM.jpg?resize=768%2C574&ssl=1 768w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2016/08/Screen-Shot-2016-08-18-at-8.49.10-PM.jpg?w=1340&ssl=1 1340w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2016/08/Screen-Shot-2016-08-18-at-8.49.10-PM.jpg?w=1240 1240w" sizes="(max-width: 620px) 100vw, 620px" data-recalc-dims="1" /></a></p> <p style="padding-left: 30px;"><strong><span style="color: #993300;"> </span></strong></p> <p><strong>Overview of the talk.</strong></p> <p><strong>Overview of the talk.  </strong>For ease of reference, here is slide-by-slide “table-of-contents” summary of the presentation.</p> <ol> <li>Title: Living High and Healthy: Why Coloradans and Others Who Live at High Altitude Live Longer, and What Flatlanders Can Learn From Them.</li> <li>Boulder has very low rates of obesity, diabetes, cardiovascular disease.  Is there a secret we can exploit to live longer?</li> <li>The obesity rate in Boulder in 2014 was 12.4%, compared with 39.5% for Cabell County, West Virginia.  Could this be due to differences in climate, topography, diet, education and income?</li> <li>No single cause explains obesity.  亚搏体育客户端下载 , exercise, genetics, and psycho-social factors all likely play a role,and it is difficult to separate cause and effect.</li> <li>Observational and interventional studies are often hard to interpret.  To identify factors with long-term effects on obesity, it is useful to look at geographic distributions, since they are less transient.</li> <li>Obesity and diabetes have been on the rise since 1994, but CDC data for the U.S. shows that their prevalence varies significantly state-to-state</li> <li>In 2004, just a decade later,  obesity rates increased sharply, but unevenly.  The Southeast showed much higher rates compared to the West, and Colorado stood out with the lowest rates in the U.S.</li> <li>And in 2014, with continued increases in both obesity and diabetes, Colorado and a few other states continued to buck the trend.  But why?</li> <li>Viewing obesity at a county level provides a sharper, more detailed view.</li> <li>As does a county-by-county view of diabetes</li> <li>Apparently, people in regions with high obesity have less access to transit eat an inferior diet</li> <li>Another explanation is that the obese are less physically active.  That’s supported to some extent by surveys, but are self-reports always reliable?  But inactivity could be as much an effect of obesity as a cause.</li> <li>It is particularly compelling to see how close a match there is between  obesity prevalence and altitude.  This is evident not only in the high plateau of the Western U.S., but also in how the “low obesity island” of the Appalacian mountains stands out from the surrounding “sea of obesity” of the Southeastern U.S.</li> <li>It’s not just the U.S.  Maps of Europe show that longevity tracks altitude.  The can be seen, for example in the mountainous regions of northern Spain, Switzerland, Croatia, Greece, Austria, Norway, Iceland, and the Scottish highlands.</li> <li>Looking at maps is interesting, but it is more convincing to look at statistics.  A survey of 422,603 adults across the U.S. — controlling for age, sex, race, ethnicity, education, employment, temperature, diet, physical activity and smoking — found the odds of being obese for those who live at sea level are 4-5 times higher than for those living at 10,000 feet or higher.  Boulder does better even that predicted, which indicates that altitude is important, but only one of many factors.</li> <li>A study of obesity among Tibetans strengthens the altitude hypothesis, because Tibetans are relatively homogeneous genetically, culturally and economically. Obesity rates dropped in half at higher altitudes.  Intriguingly, the high altitude Tibetans also consumed more calories and were more physically active.</li> <li>Why is obesity and diabetes lower at high altitude?  Exercise, ethnic distributions, UV radiation and air quality have been proposed as explanations, but their is countervailing evidence.  The most promising explanation is the drop in oxygen concentration at high altitude, creating a hypoxic environment.</li> <li>A range of studies show that hypoxia confers numerous health benefits:  reductions in body weight, diabetes, blood pressure, CVD, detention; and increases mitochondrial biogenesis and in measures of cardiovascular fitness, insulin sensitivity and glucose metabolism.</li> <li>An interventional study of 20 obese males who spent a week at the summit of the Zugspitze in Germany found spontaneous decrease in weight, blood pressure and food intake, and increases basal metabolic rate and leptin signaling, lasting even 4 weeks after return to low altitude.</li> <li>A comprehensive study of U.S. death certificates found that men and women living above 4900 fit on average had statistically longer lifespan and reduced heart disease, though there were increases in COPD.</li> <li>A study of athletes found that those who live at high altitude and train at low altitude show increases in strength and endurance, vs. those who live low and train high.  A meta-analysis of 11 similar studies found that spending time at high altitude is only beneficial if sustained for at least 9.5 hours daily for at least 2 weeks. Short term training with “hypoxic masks” appears to be ineffective.</li> <li>What mechanisms explain the connection between hypoxia and these health benefits?  Three have been proposed:  (1) hormone signaling by leptin and insulin; (2) hormetic sensing by the PGC-1α cascade; (3) inhibition of the mTOR anti-aging pathway via REDD1.  <em>(Note: For an alternative or additional mechanism, involving the elevation of CO2 levels at high altitude, see Comment #5 below by Mark L, and my follow up in Comment #6).</em></li> <li>Studies of intermittent hypoxia exposure in rates found a 6-fold increase in plasma leptin and increased leptin sensitivity</li> <li>Another rat study found that hypoxia increases brain-derived neurotrophic factor (BDNF), spurring neurogenesis and cell proliferation in the hippocampus, and eliciting an anti-depressant effect</li> <li>Hypoxia also induces production of the REDD1 protein, thereby suppressing the activity of mTOR, a master regulator of protein synthesis and growth processes. While mTOR induced growth is beneficial in youth, overactivity of mTOR is associated with obesity, diabetes and other “diseases of aging”.</li> <li>Now we get the the core idea of the presentation! I’ve pulled together an overview of these mechanisms in a single diagram, showing how hypoxia improves health by first activating a “stress sensor” called PGC-1α, a protein that binds to the PPAR-γ receptor in our cells.  PGC-1α is the master regulator of mitochondrial biosynthesis.  In turn, it stimulates the hormones FNDC5 and irisin the brain, muscles and adipose tissue, leading to a cascade of beneficial health effects.  For example, secretion of FNDC5 and irisin in the muscles promotes thermogenesis and a shift from inflammatory white fat (WAT) to metabolically active  brown fat (BAT). And in the brain, the secretion of FNDC5 and irisin results in increased BDNF and leptin signaling, insulin sensitivity, appetite suppression, and the urge to exercise.</li> <li>BDNF, or brain-derived neurotrophic factor is produced in primarily in the brain’s hippocampus and hypothalamus.  It promotes neurogenesis and brain plasticity. Notably, BDNF suppresses appetite and increases metabolic rate and is found at low levels in obese humans and animals.  But despite the name, BDNF is found “peripherally” — outside the brain — in the liver, muscles and adipose tissue.  There it modulates hormones like insulin, leptin and cortisol, and promote thermogenesis and insulin sensitivity.</li> <li>The PGC-1α cascade similarly activates autophagy, a cellular “housecleaning” process that sequesters damaged intracellular proteins within autophagosomes, digesting and disposing of this waste material, thereby enhancing cellular fitness.  Autophagy has been shown to increase longevity in animal studies.</li> <li>Autophagy promotes longevity by removing damaged intracellular proteins and pathogens, damping down inflammation, reducing apoptosis, necrosis, senescence and oncogenesis.  It also boosts the innate immune response.</li> <li>OK, so living at altitude in a hypoxic environment leads to improved health outcomes.  But do we need to move to the mountains or wear hypoxia masks to lose weight and live longer?  Fortunately, not.</li> <li>To explain why, it is useful to contrast three theories of aging:  the genetic program theory, the damage accumulation theory and the hyperfunction theory. I’ve discussed these in detail in my post, <span style="color: #993300;"><strong><a style="color: #993300;" href="//www.tennisbs.com/2015/03/live-longer/">Live Longer!</a></strong></span>.</li> <li>The genetic program theory and the damage accumulation theory have serious difficulties.  For example the theory that aging is driven by oxidative damage can’t explain long lived animals like the naked mole rat, that show extreme oxidative damage but live about 10 times longer than lab rats.  One key is that they are able to upregulate their protective endogenous defenses, like the Phase II antioxidant enzymes.  By contrast, the hyperfunction theory embraces the idea that aging results from overactivity of cellular processes like inflammation, cell division, lipogenesis, etc.  These processes are under control of the mTOR pathway.</li> <li>yabo亚洲 is one of the most useful way to counteract mTOR-driven aging processes.  yabo亚洲 is a set of defense, repair and adaptation mechanisms that are activated by low dose stressors.  Stress must be optimized such that it is high enough to stimulate a response, but not so high as to be damaging.</li> <li>There are four types of hormesis: structural hormesis, defense hormesis, metabolic hormesis, and psychological hormesis.  I’ve written about all of these in this blog.  But it is metabolic hormesis that concerns us in this talk.  Examples of metabolic hormesis are calorie restriction, exercise, cold exposure and hypoxia.</li> <li>Returning to our earlier diagram on Slide 26, it turns out that each of these other metabolic stressors — cold, exercise and calorie restriction — also activate the same PGC-1α cascade that is primed by hypoxia.  To me, this is quite a remarkable thing!  We are endowed with a general sensor for external stressors that place demands on our internal energy economy, causing major shifts in our appetite, urge to exercise, insulin sensitivity, and even the metabolic character of our fat stores!</li> <li> The universality of the PGC-1α cascade makes sense biologically, but it was a revelation to me when I saw the research that underlies this picture, and how such different activators as exercise, cold and diet can activate the same pathways.  Of course, these external forces are not all identical, because they act to different degrees in different tissues and organs.  But the underlying biochemistry is a common driver.</li> <li>Of the various effects of the hormesis-activated PGC-1α cascade, one of the most interesting is how it promotes “exercise salience” – the urge to exercise.  It does this by improving mitochondrial function, metabolic rate and thermogenesis, thus enabling the rapid release of energy on demand.  At the same time, this metabolic hormesis is effective in counteracting inflammation. Alistair Nunn and colleagues wrote a brilliant paper, proposing that the epidemic of inflammatory disorders may be a result of a sedentary lifestyle lacking in hormesis.</li> <li>Nunn contrasts the virtuous cycle of hormesis with the vicious cycle of inflammation.  In the first of these, metabolic hormesis spurs mitochondrial biogenesis, supplies ample energy, encouraging exercise and other hormetic activity, and suppressing appetite.  And hormesis tends to counteract the effect of whatever inflammation is present.</li> <li>The vicious cycle of inflammation is enabled by a lack of metabolic hormesis.  Inflammation weakens mitochondria, damping energy generation and the willingness to exercise, fast or expose oneself to cold.  The lack of energy results in heightened appetite, particularly for inflammatory “comfort foods”, and leads to a sedentary, pro-inflammatory lifestyle.</li> <li>Nunn’s brilliant paper encapsulates this view in the observation that hunter-gatherers of yore often went without food, experience extremes of temperature, and were physically active out of necessity.  Inhabitants of the contemporary world, by contrast, suffer from a shortage of hormesis,   giving rise to inflammatory diseases of civilization, and a loss of “metabolic flexibility”.</li> <li>So you don’t have to live at high altitude to reap the rewards of metabolic hormesis.  Hypoxia is not the only route to taming obesity, diabetes and metabolic syndrome.  Let yourself experience discomfort. Take cold showers, hike and lift heavy things, and eat less frequently.</li> <li>I have included three slides of references for those wanting to probe this topic more deeply.  References on altitude, obesity and health;</li> <li>References on hypoxia health effects and mechanisms;</li> <li>And references on the hormetic control of metabolism and health, particularly the PGC-1α cascade.  In the video, you can also listen to the Q&A that follow the talk.  It starts at the 28:25 minute mark.</li> </ol> <p>Here is a brief summary of the comments, questions and answers:</p> <p style="padding-left: 30px;"><strong>Q1.</strong> How much of the audience lives at high altitude?<br /> <strong>A1.</strong> Most of the audience raises their hands</p> <p style="padding-left: 30px;"><strong>Q2.</strong> Fetuses in utero compete for oxygen with the mother, experiencing hypoxia like that on top of Mt. Everest. We have evolved to adapt to a hypoxic environment.<br /> <strong>A2.</strong> Good observation, and I should comment that as with all types of hormesis, one can overdo it.  So hypoxia can represent too much stress, for example with altitude sickness or for individuals with COPD.  So you need to be aware of your health status</p> <p style="padding-left: 30px;"><strong>Q3.</strong> I heard that The Air Force Academy in Colorado was sited here in order to promote physical conditioning due to its high altitude.  Do you know if this is true?<br /> <strong>A3.</strong> I think there studies supporting this, and Olympic athletes also spend time training at high altitude for this reason.  But as I mentioned, you may need to spend several weeks at high altitude to get the full benefits.</p> <p style="padding-left: 30px;"><strong>Q4.</strong> Can you speculate comparing Boulder to Salt Lake City and Park City in Utah.  They consume less coffee and alcohol.  And among devout Mormons, the practice of fasting once a month. So are these confounding variables to the altitude effect<br /> <strong>A4.</strong> Yes, they are confounding variables.  As I mentioned, obesity, diabetes and longevity. is multi-factorial. And the map I showed had some pockets around Salt Lake City and maybe Las Vegas, where there is urbanization.  So some factors are working for you, some against you. Altitude is only one variable.  Alcohol is a hormetin.  As with all homeric things, there is an optimum level.<strong>Q5.</strong>  The CDC maps of the U.S. show that the higher the altitude, the higher the suicide rate.  It peaks in Wyoming, and is high in all the mountain states.<br /> <strong>A5</strong>.  I had read that too, and I wish I could explain it, but I can’t.</p> <p style="padding-left: 30px;"><strong>Q6.</strong> Have you looked at radiation hormesis?  Low level radiation may be healing. Cancer rates on the east coast were shown to drop where radon levels were higher.<br /> <strong>A6.</strong>  There is a whole literature on radiation hormesis which I didn’t go into in my talk. It’s more controversial, and it is harder to get conclusive data, but I think there is an effect.</p> <p style="padding-left: 30px;"><strong>Q7.</strong>   I’m interested in the connection between hypoxia and diseases of mitochondrial dysfunction.  Have you seen any data on the effect of altitude on morbidity in general from other diseases related to mitochondrial function like cancer, Alzheimer’s, Parkinson’s, etc.<br /> <strong>A7.</strong>  There were some studies I saw relating to dementia.  I couldn’t find good studies on cancer.  I cited one study in my talk on the effect of altitude and longevity.</p> <p style="padding-left: 30px;"><strong>Q8.</strong>  Is there a difference between living your whole life at high altitude vs. moving there when you are 40 or 50<br /> <strong>A8.</strong>  That’s a good question. I don’t know.</p> <p style="padding-left: 30px;"><strong>Q9.</strong>  Ultra-runners recommend that if you can’t arrive at a high altitude race site 2 weeks ahead, it is preferable to arrive just 1-2 days before the race.  Any idea what the mechanism would be and  if that argument is valid.<br /> <strong>A9.  </strong>Like anything else, hormetic stress start out being a disadvantage and their benefits take time to take hold. Hypoxia initially lowers your VO2 max, but as you get mitochondrial biogenesis, more red blood cells and hemoglobin, you get a net benefit.  But it takes several weeks.  So maybe the advice is right that if you come out just 3 or 4 days before the race you might experience a decrement in performance.</p> <p style="padding-left: 30px;"><strong>Q10.</strong>  In Big Sky, Montana, at 7500-9500 ft, we experience what you showed in your slides.  Maybe the suicide problem results from the cloudy, depressing weather.  People are active in Montana and may get depressed when they can no longer be active.<br /> <strong>A10.</strong>  The suicide observation is still a paradox to me, particularly in light of the studies  showing that hypoxia elevates BDNF levels.  It still needs some explanation.</p> <p>At the AHS16 conference in Boulder,  I also had the opportunity to present a more general overview of the biology of hormesis, covering not just “metabolic hormesis” stressors such as hypoxia, but hormesis of the other three types — structural, defense, and psychological.  Several people asked for copies of the poster, so I attach it here as a pdf file.  Feel free to download it:</p> <p style="text-align: center;"><span style="color: #0000ff;"><strong><a style="color: #0000ff;" href="//www.tennisbs.com/wp-content/uploads/2016/08/BeckerAHS16.pdf">AHS16 Poster: How yabo亚洲 Works</a></strong></span></p> <p>I think this general topic of metabolic hormesis is fascinating, and quite central to what I write about in this blog.  So I’d love to get further comments, questions and discussions going.</p> //www.tennisbs.com/2016/08/the-health-benefits-of-hypoxia/feed/ 18 5400 FAQ for vision improvement by Hormetism //www.tennisbs.com/2016/03/faq-for-vision-improvement-by-hormetism/ //www.tennisbs.com/2016/03/faq-for-vision-improvement-by-hormetism/#comments Todd Wed, 02 Mar 2016 06:33:40 +0000 Uncategorized active focusing adjustable lenses astigmatism diopters Hormetism hyperopia myopia presbyopia print pushing Snellen chart vision improvement //www.tennisbs.com/?p=5334 Three of my most popular articles are about how to restore your eyesight naturally and liberate yourself from glasses or contact lenses: Myopia: a modern, yet reversible disease Improve eyesight — and throw away your glasses 亚搏体育客户端下载 I call my general method “Hormetism” — the application of incremental stress to improve health.  While this approach has some similarities to other […] <p>Three of my most popular articles are about how to restore your eyesight naturally and liberate yourself from glasses or contact lenses:</p> <ul> <li><span style="color: #993300;"><b><a style="color: #993300;" href="//www.tennisbs.com/2014/08/myopia-a-modern-yet-reversible-disease/">Myopia: a modern, yet reversible disease</a></b></span></li> <li><span style="color: #993300;"><strong><a style="color: #993300;" href="//www.tennisbs.com/2010/07/improve-eyesight-and-throw-away-your-glasses/">Improve eyesight — and throw away your glasses</a></strong></span></li> <li><span style="color: #993300;"><strong><a style="color: #993300;" href="//www.tennisbs.com/rehabilitation/">亚搏体育客户端下载 </a></strong></span></li> </ul> <p>I call my general method “Hormetism” — the application of incremental stress to improve health.  While this approach has some similarities to other natural vision improvement methods, what is unique here is how the method is organized around the central principle of applying graduated, incremental defocus stress to induce progressive improvement over time.</p> <p>Hormetism is the precise opposite of the current standard of care for correcting vision.  Minus lenses are prescribed to provide immediate relief and “correct” a refractive error in the eye — usually a combination of axial lengthening and thickening or spasm of the crystalline lens.  But despite the immediate relief, this approach provides a “crutch” that induces a compensation in the eye that makes the myopia grow worse over time.  The method of Hormetism essentially reverses the process by using focusing techniques or plus lenses to restore the original shape of the eye and accommodative ability of the lens. The above linked blog posts delve into theory and experimental evidence for my method.</p> <p>Vision improvement by Hormetism is also the single most popular topic on my <span style="color: #993300;"><strong><a style="color: #993300;" href="http://forum.www.tennisbs.com/index.php?board=4.0">Discussion Forum</a></strong></span>, and I’m so pleased to hear from many that these articles have helped them to reduce or even eliminate their dependence on glasses — without resorting to laser eye surgery.</p> <p>But I get a constant stream of questions asking for clarifications about how to proceed.  I often find myself answering the same questions again and again.</p> <p><strong>So I’m writing this post to provide an “FAQ”:   Answers to frequently asked “practical ” questions about how to apply this method to get results and improve your vision.</strong>  I have tried to boil it down to a simple, step-by-step method.  The information and ideas summarized here are based upon my personal experience, what has worked for others, and my understanding of the science of vision.  I am not providing medical advice, so take responsibility for your own health.</p> <p><em><strong>Q1.  How do I start if I am myopic (nearsighted) and can focus close up, but the distance is blurry? </strong></em></p> <p>A1.  Follow this five step process if you are myopic:</p> <ol> <li><strong>Note your Snellen score.</strong> First go to the <strong><a href="http://www.i-see.org/eyecharts.html">ISEE Website</a> </strong>and print out a Snellen chart.  (That’s one of those eye charts you use in the doctor’s office or DMV to test your vision, like the one in the image below).  Hang it on the wall in a well lit area and mark off a line 20 feet back from the wall.  Cover each eye separately and note the lowest line for which you can correctly read all the letters.For example if it is Line 3 for your left eye and Line 4 for your right eye, your Snellen score is 20/70 (L) and 20/50 (R).  The second number after the slash represents the distance that a normal person would have to stand at to see in focus the line that you can see at 20 feet back.  Note that score, because it is your baseline against which to track improvement.<img class="wp-image-3820 aligncenter" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2012/04/Screen-Shot-2012-04-21-at-1.08.54-PM1.png?resize=302%2C349" alt="Snellen chart" width="302" height="349" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2012/04/Screen-Shot-2012-04-21-at-1.08.54-PM1.png?w=1154&ssl=1 1154w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2012/04/Screen-Shot-2012-04-21-at-1.08.54-PM1.png?resize=129%2C150&ssl=1 129w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2012/04/Screen-Shot-2012-04-21-at-1.08.54-PM1.png?resize=259%2C300&ssl=1 259w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2012/04/Screen-Shot-2012-04-21-at-1.08.54-PM1.png?resize=885%2C1024&ssl=1 885w" sizes="(max-width: 302px) 100vw, 302px" data-recalc-dims="1" /></li> <li><strong>Note your diopter correction.</strong>  This is the first number on your prescription, also called the spherical aberration.  Ignore for now all the other numbers after the first — these relate to astigmatism or cylindrical aberration.  (More about that later).  OD is the right eye and OS is the left eye.  So for example, if your prescription is<br /> ..<br /> OD -3.00 -0,.50 x 95<br /> OS -2.50 -1.00 x 93<br /> ..<br /> Then your myopia can be summarized as:<br /> ..<br /> -3.00/-2.50<br /> ..<br /> What are diopters?  Well, 100 divided by the minus diopter number is the approximate distance (in centimeters) that you can see clearly in focus with each eye.  Since there are 39.4 inches per meter, then in inches that would be 39.4 divided by the diopters.  So a person with the above prescription can see<br /> ..<br /> 39.4/3 = about 13 inches with the right eye<br /> 39.4/2.5 = about 16 inches with the left eye<br /> ..<br /> Your Snellen score and diopter correction have different meanings, so you can’t translate from one to the other.  However, if you don’t have your diopter correction, you may find this chart useful in making an approximate translation between Snellen and diopters.<br /> ..<a href="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/02/Screen-Shot-2016-02-27-at-1.43.24-PM.jpg" rel="attachment wp-att-5342"><img class="size-full wp-image-5342 aligncenter" src="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/02/Screen-Shot-2016-02-27-at-1.43.24-PM.jpg?resize=330%2C307" alt="Screen Shot 2016-02-27 at 1.43.24 PM" width="330" height="307" srcset="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/02/Screen-Shot-2016-02-27-at-1.43.24-PM.jpg?w=330&ssl=1 330w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/02/Screen-Shot-2016-02-27-at-1.43.24-PM.jpg?resize=150%2C140&ssl=1 150w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/02/Screen-Shot-2016-02-27-at-1.43.24-PM.jpg?resize=300%2C279&ssl=1 300w" sizes="(max-width: 330px) 100vw, 330px" data-recalc-dims="1" />.</a>.</li> <li><strong>Use print pushing to reduce myopia.</strong>  Print pushing is a method that involves “active focusing”.  It is not a matter of passively wearing special lenses.  It requires conscientious awareness of the reach of your focus and an intentional effort to increase that reach by “nudging” it. If your myopia is stronger than -2 diopters or 20/150 in both eyes, then you cannot see normal print in focus beyond about 20 inches.  So you can proceed to do “print pushing” <em>without any glasses or contacts</em> — just your naked eyes.  The idea behind print pushing is to read right at the limit of your focal distance, and to systematically push that distance to become farther and farther away. Print pushing is something you integrate into your normal routine of reading printed matter or computer screens.  About 5 years ago, <a href="http://forum.www.tennisbs.com/index.php/topic,8.msg781.html#msg781">I defined three distances</a> to keep in mind while print pushing:<br /> ..</p> <blockquote style="margin: 0 0 0 40px; border: none; padding: 0px;"><p><strong>D1.</strong> The ‘edge of focus’ – the furthest distance for myope (or closest for a hyperope) where a printed letter is completely in focus<br /> <strong>D2.</strong> The ‘edge of blur’ – the distance just beyond the edge of focus, where the slightest blur in the letter can just be detected<br /> <strong>D3.</strong> The ‘edge of readability’ – the furthest distance where you can intelligibly recognize each letter.</p></blockquote> <p>..<br /> Now D1 and D2 are going to be VERY close, almost exactly the same distance. If you are reading at D1, and you push the print slightly away less than an inch, you are immediately at D2. And if you are at D2 and get the tiniest distance closer, you are back at D1 again.You should spend the vast majority of your time reading at D1, in perfect focus, but continually (every few minutes), testing yourself by “pushing” into to D2. That’s because D1 is a dynamic distance, constantly changing.  It depends on lighting conditions, how alter or tired you feel, and other factors.  And you never want to be reading at D3 — that is needless stress on your eyes.The whole idea of print pushing is to keep increasing D1 and D2 so that your range of focus increases.  Once your myopia weakens sufficiently, go to Step 4.</li> <li><strong><strong>If your myopia is mild (less than about -2 diopters), you should print push with plus <img class=" wp-image-5348 alignright" src="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/02/plus-lens-rack.jpg?resize=336%2C448" alt="plus lens rack" width="336" height="448" srcset="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/02/plus-lens-rack.jpg?w=258&ssl=1 258w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/02/plus-lens-rack.jpg?resize=113%2C150&ssl=1 113w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2016/02/plus-lens-rack.jpg?resize=225%2C300&ssl=1 225w" sizes="(max-width: 336px) 100vw, 336px" data-recalc-dims="1" />lenses.<br /> </strong></strong>Once your myopia is -2 or less, you can easily read a book or computer at arms’ length — at up to about 19-20 inches (half a meter) — without glasses.  So you aren’t effectively increasing D1 and D2 any more. That’s when you need to start using “anti-corrective” lenses to make your eyes work harder, by bring D1 and D2 closer.  This is analogous to wearing ankle weights to increase leg strength when you go for a run.  This technique is sometimes known as “plus lens therapy”.Unlike minus lenses, which have concave curvature to “correct” myopia, plus lenses have a convex shape like a magnifying glass, making it easier to see objects up close.  But this also brings D2 closer, making it harder to focus in the distance.  And this is precisely what makes them useful for increasing D2 beyond 20 inches.<br /> ..<br /> Plus lenses are sometimes called reading glasses or “readers”, mainly to help people with hyperopia or presbyopia read with greater ease.  But you are going to use them for the opposite purpose — for making it harder to focus in the distance.To choose the right strength of plus lens, I recommend making a trip to your local pharmacy or department store, where these “readers” are sold on rotating racks, like those pictured to the right.Try on various pairs to find one that allows you to read comfortably at about 15-20 inches, but begins to blur beyond that.  As a rule of thumb,  your “effective” diopters will be that of your current diopters <em>minus</em> that of of the plus lens you wear.   So if you have worked your way to a -0.75 prescription, you’ll need to wear a +1.25 pair of reading glasses to make it seem like you have -2.00 diopter myopia. So try on the +1.25 pair to see how that works.<br /> ..<br /> Wear these reading glasses for at least part of the time you read each day.  How much time?  To be effective, I would say about 1-2 hours per day while reading.  You can use them more if you are comfortable.  But rest is important, so it is very important to follow these guidelines:<br /> ..<br /> – Take frequent breaks every 15-30 minutes or so, removing the glasses to look at objects near and far<br /> – Stop if you get tired, or if your eyes get sore or red<br /> – Use plus lenses only for reading and close work.<br /> ..<br /> Plus lenses will create too much blur for distance activities. (See point 5 below).As your myopia reduces, you will want to replace these plus lenses with stronger plus lenses.  Once you get higher than about +2.5, there is no need to go any higher.<br /> ..</li> <li><strong>Use under-correction for distance activities.</strong> When not reading or doing close work, you can provide further stimulus to myopia reversal by wearing slightly under-corrected glasses or contacts when at work, watching TV, sitting in lectures, or other distance viewing.  This means ordering a pair of lenses that are about 0.25 to 0.5 diopters weaker than your original lenses. So to use the earlier example, for a starting of a prescription that reads:<br /> ..<br /> OD -3.00 -0,.50 x 9<br /> OS -2.50 -1.00 x 93<br /> ..<br /> You would replace these with the following under-corrected prescription, changing only the first numbers and leaving the others alone:<br /> ..<br /> OD -2.75 -0,.50 x 9<br /> OS -2.25 -1.00 x 93<br /> ..<br /> You wear these under-corrected lenses for a while (probably a few months) until your myopia is sufficiently reduced (by the combination of print pushing and wearing weaker distance lenses).  Then you order additional lenses with further reductions in the diopter correction.  When you are looking at distance objects, trace common objects with your eyes and observe fine features, especially lines and edges.  Vary your gaze near and far, and make this into a game.  Play with it!<br /> ..<br /> <strong><em>Fusing of double images.</em> </strong>As your myopia reduces, you may have the experience that many have of “double vision” or ghosting.  This might seem alarming at first, but it is actually a sign of your ability to see objects more sharply!  I suggest watching the video on my post “Myopia: a modern yet reversible disease” for a good description of how to use a technique I call “fusing” to take advantage of double images:<br /> ..</p> <ol> <li>Find distant objects with sharp contrasting edges: telephone wires, tree branches, edges of buildings or signs</li> <li>Focus on the darker of the double image and away from the fainter image.  With time, the darker image will become darker, and the fainter image will fade away</li> <li>Eventually the double image with fuse into a single crisp image — very exciting!</li> </ol> <p>..<br /> As your myopia reduces, you will start being able to see objects in perfect focus at increasing distances, even with your naked eye!  This is where the technique really pays off and it is exciting and even emotional to experience this.</li> </ol> <p><em><strong>Q2.  This all sounds great, but I have hyperopia (far sightedness) or presbyopia (reduced accommodation of the crystalline lens) that make it hard for me to read fine print or read up close?  What can I do about that?</strong></em></p> <p>A2. Well, if you understand the principle of how Hormetism works to reduce myopia, you should be able to answer that question if you think about it for a moment?  What do you think the answer is?  That’s right — it’s the same method applied in the opposite direction!</p> <p>When you read, instead of print pushing do “print pulling”.  Define D1, D2 and D3 by moving inward from perfect focus starting at D1.  Generally you can print pull with your naked eye.  Get as close as you can to read at D1, and test yourself frequently by getting closer to the text.  And try to test yourself on finer and finer print.  You can also print out a <strong><a href="http://www.i-see.org/block_letter_eye_chart.pdf">near vision test card</a></strong> from the I-SEE website  It’s basically a Snellen chart for people with hyoperopia or presbyopia. (It is on the final page of that link, after the standard Snellen chart for distance vision).</p> <p>Another cool way to improve near vision is to use the “convergence” method of Ray Gottieb.  You can <strong><a href="http://www.i-see.org/gottlieb/presbyopia_chart.pdf">print out his chart and directions</a></strong> from the I-SEE Website.  This is a bit tricky and involves learning to allow your eyes to relax enough that they “cross” slightly.  Not everyone can do this.  It took me a while to make it work for me, but once I got it it was like magic!  Try it, it may or may not work for you.</p> <p><em><strong>Q3. My myopia correction is much stronger in one eye than the other. How do I apply your method?</strong></em></p> <p>A3.  If  the prescriptions for your right and left eyes are within 0.5 diopters of each other (as in the above example), then you should not have any difficulty doing print pushing. But if they differ by more than 0.5 diopters, then your D2 can be more than a few inches different for the right and left eyes.  So you can’t find a single distance for print pushing that will work for both eyes.</p> <p>As we age, it is common to develop a condition called “mono vision” where the eyes tend to specialize — one is better at distance, one for close work.  This is the case with me, where my right eye has perfect distance vision but some presbyopia close up, whereas the the left eye is much sharper close up but 20/40 for distance.  The two eyes work very well together, but I keep pushing each eye to improve where it is weak.  I do print pushing with my left eye and print “pulling” with my right eye, as explained in the answer to Question 2 above.</p> <p><img class="size-full wp-image-5354 alignright" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2016/03/Wink.jpg?resize=620%2C454" alt="Wink" width="620" height="454" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2016/03/Wink.jpg?w=696&ssl=1 696w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2016/03/Wink.jpg?resize=150%2C110&ssl=1 150w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2016/03/Wink.jpg?resize=300%2C220&ssl=1 300w" sizes="(max-width: 620px) 100vw, 620px" data-recalc-dims="1" />In such a case, I would advise to work on the eye with a higher degree of myopia first.  But to do that you have to prevent your better “stronger” eye from doing the work, so that your “weaker” eye is forced to improve.  There are several alternative ways to selectively work on just your weaker eye, depicted in the diagram to the right::</p> <ol> <li><strong>Patch.</strong> One way to do that is to tape some paper over the lens of the stronger eye.  I recommend using wax paper or tracing paper that diffuses the image and prevent focusing, but lets in enough light to keep your pupil from constricting, so you don’t have to readjust to the light when removing the glasses. Patching is convenient, but you may feel it looks too awkward or “nerdy” in public.</li> <li><strong>Shield.</strong>  I personally like this method when reading for a long time.. Hold one hand with thumb against nose, and tilt at a 45 degree angle to block the stronger eye’s direct view of text, but still allow light in.  Your strong eye will be “looking” at the backside of your tilted hand, but your brain will fill in the gap and “see” what your weak eye sees on the page you are reading.</li> <li><strong>Wink.</strong>  This is similar to shielding, but is leaves both hands free and is the least “conspicuous”.  At first, you may find it tiresome to hold one eye blinked shut, but it is amazing how much easier and almost effortless this becomes with practice.  I can blink one eye shut for 5 minutes without any problem.  And I periodically “flash” it open every minute or so to keep the pupil from shutting down.  This is something you can even do while driving because there is no issue of reaction time to open both eyes.</li> </ol> <p><em><strong>Q4.  Glasses are expensive. Do I have to keep buying new pairs of glasses as my vision improves?</strong> </em></p> <p>A4.  I agree that it would be costly to have to buy a new pair of glasses every time your vision improves.  There are two alternatives I can recommend if you want to save money and are willing to compromise a bit on style:</p> <ol> <li><strong>Buy some inexpensive glasses online.</strong>  There are many vendors, but a reliable one is: <a href="http://www.zennioptical.com">zennioptical.com</a>.  They have a wide range of choices of frames, including some under $20, and you can just input your prescription.  It is then relatively painless to order additional pairs with successively weaker corrections.</li> <li><strong>Buy adjustable lenses.</strong>  You can buy these from <a href="https://adlens.com">adlens.com</a> or <a href="https://www.eyejusters.com">eyejusters.com</a>. Adjustable lenses have the advantage that you can continuously alter the prescription so that it is fine tuned to what you need.  Some adjustable lenses can be adjusted both as plus lenses for print pushing, and under-corrected minus lenses for distance activities, and even minus lenses for print pulling.  I have been experimenting with using them to work on reducing the extent of my own mono vision (slight myopia in the left eye and slight presbyopia/hyperopia in the right eye).  This is a nice all-purpose solution.  The main downside is that these glasses have a somewhat reduced field of vision and tend to have a little bit of distortion that can be annoying.  But very practical.</li> </ol> <p>For the record, I have absolutely no connection or financial interest in any of these sites, or any product whatsoever. I have myself purchased glasses from both Aennioptical and Adlens and have been satisfied, but I make no promises or claims as to how well these products will work for you.  But they are cheap enough that you can afford to experiment and to work through several stages of improvement without spending a bundle of money.</p> <p><em><strong>Q5. I have very strong myopia (usually between -6 to -12 diopters).  Will this method work for me or is it hopeless? How long will it take me to get to 20/20?</strong></em></p> <p>A5.  The Hormetism method can work no matter how strong your myopia or how old you are.  But you need to be realistic.  It took you many years to become myopic, and it will require patience, consistency and time to undo the damage.  The rate of improvement varies  a lot and depends on many factors, including age, genetics, and diet — and very much on your own consistency and persistence.  Some people can reduce 2 diopters in a year.  Others, only 0.5 diopters per year.</p> <p>My experience– and that of many who have shared their experience on the <span style="color: #993300;"><strong><a style="color: #993300;" href="http://forum.www.tennisbs.com/index.php?board=4.0">Discussion Forum</a></strong></span> — is that improvements do not occur at a steady rate.  Rather, you will improve in sudden, unpredictable spurts.  You may see absolutely no improvement for weeks – and then one day you find yourself more easily reading books, or you can clearly see flowers in full focus on the other side of the room.  So be patient if you don’t make any progress in the first few weeks, or if you stall after a few months.</p> <p>And let’s be clear also that some people make a concerted effort and never improve.  But there is really not much downside to trying, right? And you are not exposing yourself to the risks of other more invasive and “irreversible”  methods like laser eye surgery.</p> <p>At the very least, you may stabilize your vision and stop the further progression of myopia.  <a href="https://www.youtube.com/watch?v=XEoLV6CPJs8">Otis Brown</a> champions this as “myopia prevention” and works with young people and their parents to help them stall myopia before it becomes serious.</p> <p>Don’t minimize the potential impact of diet.  <a href="http://onlinelibrary.wiley.com/doi/10.1034/j.1600-0420.2002.800203.x/epdf">Cordain’s research</a> indicates that the standard American diet, high in sugar and industrial oils, low in fiber, omega-3 oils, and phytonutrients is likely a strong contributor to the myopia epidemic.  I found that when I went on a mostly Paleo diet, my visual acuity sharpened, and I notice that consuming cod liver oil and more brightly pigmented vegetables induced a dramatic brightening in colors at the red and purple end of the spectrum, and better night vision.  If you practice hormetic eye exercises, but eat a lousy diet, you may be working at cross-purposes to your goal of improved vision.</p> <p><em><strong>Q6. I have astigmatism.  Will this method help me?</strong></em></p> <p>A6. Astigmatism often reduces spontaneously as myopia is corrected.  That is what I found in my own case.  But you may also wish to experiment with specific <a href="http://vision-training.com/en/Training/Astigmatism/index.htm">astigmatism reduction exercises</a> such advocated by Leo Angart, such as tracing with your eyes the spokes of the <a href="http://vision-training.com/en/Download/Astigmatism/Astigmatism%20chart%20black%20on%20white.pdf">Tibetan wheel</a>, or the the similar <a href="http://cleareyesight-batesmethod.info/id40.html">Astigmatism Wheel </a>used by followers of the Bates Method.  I don’t follow the general approach of either Angart or Bates, but happily borrow specific techniques where they prove useful.</p> <p>I think that the above six questions account for about 90% of the questions I receive via individual correspondence or see posted as comments to previous posts or on the Discussion Forum.  For those who wish to take a deeper dive, I encourage you to head over to the discussion forum and peruse the many insightful discussions on vision improvement, mostly on the this popular board:</p> <p><span style="color: #993300;"><strong><a style="color: #993300;" href="http://forum.www.tennisbs.com/index.php?board=4.0">Discussion Forum: 亚搏体育客户端下载 </a></strong></span></p> <p>If your questions still are not answered by this blog post or what you find on the Discussion Forum, go ahead and start a new three to ask the question or describe your  experience.  I see a lot of good ideas over there and am constantly learning and tweaking my own approach.</p> <p>Happy seeing!</p> <p> </p> <div class="texe"> <p> </p> <p> </p> </div> <p> </p> //www.tennisbs.com/2016/03/faq-for-vision-improvement-by-hormetism/feed/ 107 5334 Is charred meat bad for you? //www.tennisbs.com/2015/09/is-charred-meat-bad-for-you/ //www.tennisbs.com/2015/09/is-charred-meat-bad-for-you/#comments Todd Mon, 07 Sep 2015 05:54:41 +0000 Uncategorized acrylamide AGEs cancer chimpanzees cooking CYP3A4 Cytochrome P450 fire gorillas grilling HCAs Homo erectus yabo亚洲 meat PAHs Richard Wrangham toxicology toxins xenobiotic metabolism //www.tennisbs.com/?p=5211 As the end of summer approaches, you love to grill your food on the open flame.  You savor that char-grilled flavor on your meat or fish.  Perhaps you fashion yourself as a modern-day caveman, inspired by the Paleo 亚搏体育客户端下载 and getting back to Nature. At the same time, you’ve probably heard that eating grilled meat is […] <p><a href="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/images.jpeg"><img class="alignright size-full wp-image-5218" src="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/images.jpeg?resize=275%2C183" alt="images" width="275" height="183" srcset="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/images.jpeg?w=275&ssl=1 275w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/images.jpeg?resize=150%2C100&ssl=1 150w" sizes="(max-width: 275px) 100vw, 275px" data-recalc-dims="1" /></a>As the end of summer approaches, you love to grill your food on the open flame.  You savor that char-grilled flavor on your meat or fish.  Perhaps you fashion yourself as a modern-day caveman, inspired by the Paleo 亚搏体育客户端下载 and getting back to Nature.</p> <p>At the same time, you’ve probably heard that eating grilled meat is a bad idea, because compounds in the meat char can cause cancer.</p> <p>According to the <a href="http://www.cancer.gov/about-cancer/causes-prevention/risk/diet/cooked-meats-fact-sheet#q3">National Cancer Institute</a>, grilling meat to the point of charring causes the formation of heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), and Maillard reaction products such as acrylamide (AA) or advanced glycation end-products (AGEs).  HCAs and AGEs are formed when the amino acids, sugars and creatine in meat react at high temperatures. PAHs are formed when meat fats burn.  Maillard reaction products are those tasty brown “caramelized” substances produced by the reaction of sugars and amino acids when meats and other foods are cooked by grilling, baking, frying or toasting.</p> <p>The National Cancer Institute reports that HCAs, PAHs and acrylamide have been shown to cause cancer in laboratory animals.  Added to this are a number of epidemiological studies purporting to show an association between consumption of cooked meats and cancer.</p> <p>So you reluctantly curtail your inner caveman and carefully scrape the blackened parts off your meats, or grill them at a lower temperature.  Or perhaps you avoid grilling altogether, retreating indoors and lightly sautéing or boiling your meat dishes.</p> <p>Relax. I’m here to make the case that charred meat is not to be feared.  It may actually be good for you, hormetically boosting your general ability to neutralize and dispose of dietary toxins. In this blog post, we will take a closer look at the animal and human studies, combined with a deeper look at the evolutionary record, aided by the perspective of modern toxicology.  I think it may change your mind.</p> <p><span id="more-5211"></span></p> <p><strong>Conventional wisdom.  </strong> It’s not just Mainstream Health that pushes the idea that charred meat causes cancer.  Even Paleo advocates like <a href="http://www.marksdailyapple.com/is-gently-cooked-food-better-for-you/#ixzz3E14ZubND">Mark Sisson </a>warn against the dangers of grilling and cooking meats at high temperatures:</p> <blockquote><p>But there’s a dark side to cooking. Depending on the methods and ingredients you use and the temperature you apply, cooking can create carcinogenic and toxic compounds, and oxidized fats – and these may be involved in some of the diseases studied. It may not be the meat itself, but how we treat the meat. …The easiest way to minimize your exposure to heat-related toxins is to emphasize gentle cooking methods and de-emphasize higher heat methods.</p></blockquote> <p>Sisson cites the usual culprits — HCAs, AGEs, acrylamide — and oxidized lipids.  He cautions particularly againt “grilling over an open flame – the worst”, pointing to its association with higher levels of HCA.  He recommends gentle methods such as steaming, poaching, boiling, braising, simmering and baking.</p> <p><a href="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-1.jpeg"><img class="alignleft size-full wp-image-5237" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-1.jpeg?resize=311%2C162" alt="Unknown-1" width="311" height="162" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-1.jpeg?w=311&ssl=1 311w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-1.jpeg?resize=150%2C78&ssl=1 150w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-1.jpeg?resize=300%2C156&ssl=1 300w" sizes="(max-width: 311px) 100vw, 311px" data-recalc-dims="1" /></a>We should be a bit suspicious of these claims, given the fact that humans have been cooking meat over open flames for more than millenium, inevitably creating char. If these claims were correct, we’d expect to see elevated rates of cancer among modern hunter-gathers who cook their meat — but we don’t.  Just as the demonization of meat and saturated fat as agents of disease has been challenged by reappraisals of epidemiological and biomedical evidence, I think we should take a closer look at the shibboleth that charbroiling meat or otherwise cooking it at high temperatures poses a health risk.</p> <p><strong>The studies.</strong> Let’s look more closely animal and human studies which gave rise to these concerns about the compounds in grilled meats.  Here’s what the <a href="http://www.cancer.gov/about-cancer/causes-prevention/risk/diet/cooked-meats-fact-sheet#q3">National Cancer Institute</a> actually says about the studies of HCAs and PAHs:</p> <ul> <li>In many experiments, rodents fed a diet supplemented with HCAs developed tumors of the breast, colon, liver, skin, lung, prostate, and other organs. Rodents fed PAHs also developed cancers, including leukemia and tumors of the gastrointestinal tract and lungs.</li> <li>However, the doses of HCAs and PAHs used in these studies were very high—equivalent to thousands of times the doses that a person would consume in a normal diet.</li> <li>Population studies have not established a definitive link between HCA and PAH exposure from cooked meats and cancer in humans. One difficulty with conducting such studies is that it can be difficult to determine the exact level of HCA and/or PAH exposure a person gets from cooked meats.</li> <li>Although dietary questionnaires can provide good estimates, they may not capture all the detail about cooking techniques that is necessary to determine HCA and PAH exposure levels.</li> </ul> <div> <p>So<img class="alignright size-full wp-image-5234" src="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/images-1.jpeg?resize=356%2C116" alt="images-1" width="356" height="116" srcset="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/images-1.jpeg?w=356&ssl=1 356w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/images-1.jpeg?resize=150%2C49&ssl=1 150w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/images-1.jpeg?resize=300%2C98&ssl=1 300w" sizes="(max-width: 356px) 100vw, 356px" data-recalc-dims="1" /> the NCI concludes that there is <strong><em>no direct evidence in humans </em></strong>that HCA and PAH from cooked meats causes cancer in humans.  The argument is based upon <em><strong>extrapolation from studies in mice and rats</strong></em>.</p> <p>Even if you are worried about PAHs, there is nothing distinctive about meats. A <a href="http://www.saveva.com/domamAcsa/pub/acsa/html/ca/dir1538/dn1538/jfp-03-pah.pdf">2003 Spanish study</a> of actual measured dietary exposures to PAHs, found that vegetables, fruits, cereals and milk all have comparable or higher levels of PAH than meat.  The average male in Spain who consumes these foods raises his risk of cancer by a 5-in-a million chance.</p> </div> <p><strong>What about acrylamide?</strong>  According to the <a href="http://www.cancer.org/cancer/cancercauses/othercarcinogens/athome/acrylamide">American Cancer Society</a>, “Based on the studies done so far, it’s not yet clear if acrylamide affects cancer risk in people.” They further state:</p> <blockquote><p>Acrylamide has been found to increase the risk of several types of cancer when given to lab animals (rats and mice) in their drinking water. The doses of acrylamide given in these studies have been as much as 1,000 to 10,000 times higher than the levels people might be exposed to in foods. It’s not clear if these results would apply to people as well, but in general it makes sense to limit human exposure to substances that cause cancer in animals.</p></blockquote> <p>Writing for the <a href="http://www.oehha.ca.gov/prop65/pdf/c-13acshattach.pdf">American Council on Science and Health</a>, Joseph Rosen of Rutgers University criticized the rodent studies as flawed, based on the extreme levels, the mode of administration, and key differences between the endocrine organs of humans and rats, where tumors were noted.  Based on the animal studies, Rosen concluded that <span style="line-height: 1.5;">“There is no credible evidence that acrylamide in food poses a human cancer risk.”</span></p> <p>What about studies of acrylamide specifically in humans?  <span style="line-height: 1.5;">A </span><a style="line-height: 1.5;" href="http://www.telegraph.co.uk/news/uknews/1571290/Study-finds-acrylamide-link-to-cancer-in-women.html">2007 Dutch study</a><span style="line-height: 1.5;"> linked acrylamide consumption to cancer in women, finding that women who absorbed more acrylamide were twice as likely to develop ovarian or womb cancer as those who ingested a smaller amount.  But a closer look at this study revealed that the measure of acrylamide was based upon a self-reported food questionnaire, not actual clinical measurements.  And there was no clear linkage specifically to meat consumption. As noted by <a href="http://www.telegraph.co.uk/news/uknews/1571290/Study-finds-acrylamide-link-to-cancer-in-women.html">Dr. Lesley Walker of Cancer Resarch UK</a>:</span></p> <div> <blockquote><p>Women shouldn’t be unduly worried by this news…It’s not easy to separate out one component of the diet from all the others when studying the complex diets of ordinary people. And as acrylamide levels are highest in carbohydrate containing foods – such as chips and crisps – other factors need to be firmly ruled out, especially being overweight or obese, which we know is strongly linked to womb cancer and probably linked to ovarian cancer.</p></blockquote> <p>As Dr. Walker notes, it is misleading to connect the potential dangers of acrylamide specifically to meat, since levels are much higher in <strong><span style="text-decoration: underline;"><em>other</em></span></strong> foods, particularly high carbohydrate foods.  According to the <a href="http://www.cancer.org/cancer/cancercauses/othercarcinogens/athome/acrylamide">American Cancer Society</a>, “Acrylamide is found mainly in plant foods, such as potato products, grain products, or coffee. Foods such as French fries and potato chips seem to have the highest levels of acrylamide, but it’s also found in breads and other grain products. Acrylamide does not form (or forms at lower levels) in dairy, meat, and fish products.”</p> <p><a href="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown.jpeg"><img class="alignright size-full wp-image-5236" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown.jpeg?resize=259%2C194" alt="Unknown" width="259" height="194" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown.jpeg?w=259&ssl=1 259w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown.jpeg?resize=150%2C112&ssl=1 150w" sizes="(max-width: 259px) 100vw, 259px" data-recalc-dims="1" /></a>For an eye opener, consult the <a href="http://www.fda.gov/food/foodborneillnesscontaminants/chemicalcontaminants/ucm053549.htm">FDA’s survey of acrylamide levels in food</a>. If you are worried about acrylamide, you might start by cutting out Ore Ida french fries (with 1098 ppb acrylamide), Hershey’s cocoa (909 ppb), Health Valley Original Oat Bran Graham Crackers (1540 ppb), Ak-mak 100% whole wheat stone ground sesame crackers (343 ppb), Safeway pitted olives (226 ppb) or Starbucks coffee (175 ppb).   By contrast,  none of the meat products on the FDA list had more than 100 ppb; many had undetectable levels.</p> </div> <p>In short, if you are concerned about acrylamide, there are more worrisome places to look than meats.</p> <p><strong>Evolution and dietary adaptation.  </strong>But are mice and rats a valid model for assessing the toxicity in humans of compounds from cooked foods?  Rodents may indeed be suitable animal models for many aspects of human physiology and toxicology, such as testing the safety of drugs, synthetic chemicals, and evolutionarily novel compounds. But animal models are mainly useful for understanding human physiological responses only where there are shared metabolic, immune, or detoxification pathways.  This is of particular importance in toxicology, because what is toxic to one species is often harmless or even beneficial to another. Detoxification pathways vary considerably across species.  For example, chocolate can poison dogs because the active ingredient, theobromine, is highly toxic to canines, while humans typically tolerate it well, and even find it to be beneficial. So if you relied on dog testing to determine your food choices, you would never eat another piece of chocolate.</p> <p>Organisms evolve detoxification processes that respond to what they are likely to encounter in their diets and their environments. Humans have been cooking (and burning) food over hot flames since they diverged from other primates half a millennia ago, so they have had ample opportunity to adapt their detoxification responses to the compounds present in charred meat.  It’s just not novel for us.</p> <p>However, to the best of my knowledge, mice and rats don’t cook their meat — with or without fire.  Meat char represents a novel toxin to rodents, so they are unlikely to have developed a strong system for detoxifying HCAs, PAHs, or acrylamide.   Thus, rodents are not a reasonable model for assessing the toxicity of compounds produced by cooking meat.</p> <p><strong>The barbecuing species.</strong>  There is compelling evidence that humans evolved to eat and thrive on a diet that includes fire-cooked foods – both meat and plants.</p> <p><strong><a href="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/the_hunt2-1.jpg"><img class="alignleft wp-image-5235" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/the_hunt2-1.jpg?resize=324%2C182" alt="the_hunt2-1" width="324" height="182" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/the_hunt2-1.jpg?w=456&ssl=1 456w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/the_hunt2-1.jpg?resize=150%2C84&ssl=1 150w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/the_hunt2-1.jpg?resize=300%2C168&ssl=1 300w" sizes="(max-width: 324px) 100vw, 324px" data-recalc-dims="1" /></a></strong>The evidence comes from several independent and reinforcing lines of evidence.  While the idea of “man as cook” goes back at least to the anthropologist Claude Levi-Strauss, his main interest was in how cooking changed social psychology.  The most comprehensive and convincing argument for the “cooking hypothesis” is laid out by Richard Wrangham in his 2009 masterpiece,  <a href="http://www.amazon.com/Catching-Fire-Cooking-Made-Human/dp/1491574615">Catching Fire, How Cooking Made us Human</a>.</p> <p>Wrangham supports his contention that cooking shaped human biology with several independent lines of evidence — including the findings of archaeology, anthropology, nutrition, evolutionary biology and physiology.  I’ll try to summarize here the key elements and implications of Wrangham’s argument:</p> <ol> <li><strong>Archaeology.</strong> Based on excavation of artifacts like burnt bones at campsites, archaeologists trace the origins of cooking by fire to physical evidence dated to less than million years ago, but other evidence suggests the advent of cooking may have been between 1 and 2 million years ago.  The timing of these archaeological events are mirrored in simultaneous dramatic changes in the teeth, jaws, digestive apparatus and brain of our human ancestors, most particularly <em>Homo erectus</em>, between 1-2 million years ago, as elaborated in Point #4 below.</li> <li><strong>Anthropology.</strong>  Cooking is practiced in every human society, including by <a href="http://hunter-gatherers.org/what-hunter-gatherers-eat.html">modern hunter-gatherers</a>. Hunter-gatherers lived in a wide variety of environments including deserts, mountains, the arctic and rain forests — but cooking is universal. While foods like fruits, organ meats, grubs and fish are typically eaten raw, most hunter-gatherers prefer to cook their meat, eggs and tubers.</li> <li><strong>Nutrition.</strong> Cooking food dramatically increases the palatability, digestibility, tenderness and available caloric value of both meat and plants. Cooking meat and other protein denatures it, rendering it more accessible to the action of digestive enzymes.  The benefits of cooking are not restricted to meats — cooking also makes plant foods more digestible.  Given the limited availability and lean composition of meat in the tropics, equatorial hunter-gathers also need to consume plant carbohydrates, such as starchy tubers.  Cooking gelatinizes the starch, increasing its glycemic index, and making it easier to digest and absorb its sugars that one could otherwise obtain from raw starch.  Raw foodism is effective as a weight loss diet because uncooked food provides less caloric value and requires more energy and time to digest than cooked food.  Domestic animals grow faster and fatter on cooked food containing the same caloric content as the equivalent uncooked food.</li> <li><strong><a href="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/images-2.jpeg"><img class="alignright wp-image-5258" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/images-2.jpeg?resize=300%2C225" alt="images-2" width="300" height="225" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/images-2.jpeg?w=240&ssl=1 240w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/images-2.jpeg?resize=150%2C113&ssl=1 150w" sizes="(max-width: 300px) 100vw, 300px" data-recalc-dims="1" /></a>Evolutionary biology.</strong>  More nutritive and tender cooked food “remodeled” the bodies of early humans, enabling the evolution of a weaker jaw, smaller teeth, and a smaller digestive tract. Gorillas and chimpanzee are mainly herbivores. They have large molars to chew plant foods, and voluminous stomachs and large intestines capable of digesting and fermenting fiber from plants.  By contrast, humans are less able than apes to digest, ferment and utilize fiber — largely because eating cooked food reduces the need for this capacity. The tenderness of cooked food enabled the human jaw and teeth to shrink.  Human jaws and molars are the smallest of any primate species, relative to body mass.  As a result of their more nutrient-dense cooked diet, humans eat half as much per pound of body weight as do great apes. The shift to a cooked meat diet also coincided with a doubling of the size of the brain of <em>Homo erectus</em> relative to that of <em>Homo habilis</em> and earlier hominids.  The “expensive tissue hypothesis” holds that more nutritive cooked food dramatically increased the energetic efficiency and intelligence of humans, freeing us from time spent gathering and digesting, increasing hunting and migration range and propelling reproductive success.</li> </ol> <p><strong>The evolution of toxicity.</strong>   One of the corollaries of the shift from raw to cooked food by early humans was a re-tooling of their sensitivity to and tolerance for dietary toxins.  Wrangham draws out some very important, but often overlooked, consequences of this evolutionary change:</p> <blockquote> <div> <p>Beyond reducing the size of teeth and guts, the adoption of cooking must have had numerous effects on our digestive system because it changed the chemistry of our food. Cooking would have created some toxins, reduced others, and probably favored adjustments to our digestive enzymes….Take, for example, Maillard compounds, such as heterocyclic amines and acrylamide…They occur at low concentration in natural foods but under the influence of heat their concentration becomes much higher than what is found in nature…They can also induce a chronic state of inflammation, a process that raw-foodists invoke to explain why they feel better on raw diets. The cooking hypothesis suggests that our long evolutionary history of exposure to Maillard compounds has led humans to be more resistant to their damaging effects than other mammals are. It is an important question because many processed foods contain Maillard compounds that are known to cause cancer in other animals. Acrylamide is an example. In 2002 acrylamide was discovered to occur widely in commercially produced potato products, such as potato chips. If it is as carcinogenic to humans as it is to other animals, it is dangerous. If not, it may provide evidence of human adaptation to Maillard compounds, and hence of a long exposure to heated foods.</p> </div> </blockquote> <p>So while humans have adapted to better tolerate “toxins” like Maillard compounds in cooked foods, the converse is true for certain plant toxins that we expect apes to tolerate better than humans.  Wrangham observes how this shift is readily demonstrated by differences in palatability and food preference between our species and the apes:</p> <blockquote> <div> <p><a href="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-2.jpeg"><img class="alignright size-full wp-image-5244" src="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-2.jpeg?resize=243%2C207" alt="Unknown-2" width="243" height="207" srcset="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-2.jpeg?w=243&ssl=1 243w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-2.jpeg?resize=150%2C128&ssl=1 150w" sizes="(max-width: 243px) 100vw, 243px" data-recalc-dims="1" /></a>In my experience of sampling many wild foods eaten by primates, items eaten by chimpanzees in the wild taste better than foods eaten by monkeys. Even so, some of the fruits, seeds, and leaves that chimpanzees select taste so foul that I can barely swallow them. The tastes are strong and rich, excellent indicators of the presence of non-nutritional compounds, many of which are likely to be toxic to humans—but presumably much less so to chimpanzees….The shifts in food preference between chimpanzees and humans suggest that our species has a reduced physiological tolerance for foods high in toxins or tannins. Since cooking predictably destroys many toxins, we may have evolved a relatively sensitive palate. By contrast, if we were adapted to a raw-meat diet we would expect to see evidence of resistance to the toxins produced by bacteria that live on meat. No such evidence is known. Even when we cook our meat we are vulnerable to bacterial infections….The best prevention is to cook meat, fish, and eggs beyond 140º F (60º C), and not to eat foods containing unpasteurized milk or eggs. The cooking hypothesis suggests that because our ancestors have typically been able to cook their meat, humans have remained vulnerable to bacteria that live on raw meat….We fare poorly on raw diets, no cultures rely on them, and adaptations in our bodies explain why we cannot easily utilize raw foods. Even vegetarians thrive on cooked diets. We are cooks more than carnivores.</p> </div> </blockquote> <p>Wrangham’s “cooking hypothesis” is certainly intriguing.  But is there any hard evidence that humans and apes (to say nothing of mice) actually have different detoxification mechanisms going on in their bodies?</p> <div>I believe the answer is yes, but we first need a brief detour into basic toxicology to understand how mammals deal with dietary toxins.</p> <p><b>Detox 101. </b> All organisms process and detoxify “foreign” or poorly tolerated compounds (including alcohol, caffeine and prescription drugs) by a process called “xenobiotic metabolism. (“xeno” = foreign).  While the liver is our primary organ of detoxification, cells throughout the body have the ability to detoxify.  The key point to understand is that detoxification occurs in two steps — <a href="http://www.carahealth.com/health-conditions-a-to-z/digestive-system/detox/365-phase-1-and-2-liver-detoxification-pathways60.html">Phase I and Phase II</a>:</p> <ul> <li><strong>The Phase I detoxification system</strong> primarily employs what is known as the Cytochrome P450 system to modify toxins.  The Cytochrome P450 (CYP) system varies by species and occurs in all life forms: animals, plants, microbes — even in viruses.  In humans, CYP enzymes are located not just in the liver, but also in the mitochondria or endoplastic reticulum of cells in most tissues of the body.  The CYP enzymes work by chemically modifying (hydrolyzing, oxidizing or reducing) the toxins into less harmful, more soluble compounds.  However, the end products of Phase I are typically reactive a “free radicals” that are <em><strong>often potential carcinogens if they persist in excessive amounts</strong></em>.</li> <li><strong>The Phase II detoxification system</strong> is a separate set of enzymes that render the products of Phase I less harmful by “conjugating” them – that is, combining their reactive groups with cysteine, glycine or sulfur molecules to create unreactive, water soluble compounds that are readily excreted in the urine or bile.</li> </ul> <p>So what do we know about how our Phase I and Phase II enzymes handle the compounds in our cooked food diet? Let’s look at Phase 1 and Phase II separately.</p> <p><strong>Phase 1 enzymes and the human diet.</strong>  As noted in <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683693/">an excellent study by Kumar et. al. (2009)</a>, the single most important and abundant Phase I enzyme is humans is called CYP3A4.  It is found not just in the liver, but throughout our bodies. CYP3A4 accounts for 30% of all the P450 enzymes expressed in the liver and about 80% of the CYP enzymes in the intestine!  According to Kumar et al, CYP3A4 is considered “the most important drug-metabolizing enzyme in humans, due to abundance, wide spectrum and indelibility.”</p> <p><em><strong>Now here is an amazing fact.  </strong></em>Despite the fact that we share 99% of our DNA with chimpanzees, we humans have developed a very different detoxification system.  Our CYP system has changed enormously since the evolutionary split from chimps.  Our most prevalent detox enzyme, CYP3A4, is found at about twice the level, and in a changed form, in humans relative to chimpanzees. According to Kumar et al. “CYP3A4 evolution in the human lineage would most likely reflect the adaptation to a change in the physiology or environment of our direct ancestors.”</p> <p>While the human CYP3A4 for the most part has similar breadth and specificity of activity against toxins as the chimp version, the is one interesting exception: unlike the chip enzyme, the human variant very active in  deactivating (“de-benzylating”)  a toxic bile acid compound known as lithocholic acid (LCA).  As Kumar notes,</p> <blockquote><p>The activation of human CYP3A4 by LCA reported in our present work would be expected to increase the detoxification of this and other bile acids metabolized by the enzyme, although this remains to be formally demonstrated. In contrast to LCA, no activation differences were detected in response to the less toxic LCA precursor chenodeoxycholic acid and the other major primary bile acid, cholic acid. This suggested a previously unknown defense mechanism against LCA-mediated cholestasis, which evolved after the split of the common human-chimpanzee lineage. The physiological necessity of such a mechanism may be related to our ancestors, beginning with <em>Homo erectus</em> some 1.8 million years ago, having adapted to an energy-dense, meat-based diet. Contemporary human foraging populations derive more than half of their dietary energy from animal foods, in comparison with 5 to 10% observed in chimpanzees. This adaptation may have been a prerequisite for the subsequent dramatic increase in the brain size in the human lineage. It is noteworthy that meat-based diet increased the load of animal steroids and thus the risk of cholestasis.</p></blockquote> <p>In short, the explosive increase of a single detoxifying enzyme, CYP3A4 is a kind of “molecular archeology” that points to the human adaptation to a cooked meat diet.</p> <p>Interestingly, CYP3A4 is also  <a href="http://www.ncbi.nlm.nih.gov/pubmed/23845848">induced by  PAH compounds</a>, one of those “compounds of concern” associated with charred meat.  In other words, humans are much better adapted than chimpanzees to detoxifying potential meat toxins.</p> <p><strong>Phase 2 enzymes and the human diet.</strong>  Now let’s look at how well humans deal the the reaction products of the Phase 1 system.  In Phase II, the altered toxins from Phase I are conjugated and neutralized to form easily excreted compounds by the Phase II antioxidant enzymes.  The Phase II system, sometimes called the Antioxidant Response Element (ARE) consists of endogenous antioxidant enzymes such as</p> <ul> <li>glutathione reductase</li> <li>glutathione transferase</li> <li>glutathione peroxidase</li> <li>glucuronysyl transferase</li> <li>quinone reductase</li> <li>epoxide hydrolase</li> <li>superoxide dismutase</li> <li>gamma glutamylcysteine</li> </ul> <p>In an earlier post, <a href="//www.tennisbs.com/2011/03/the-case-against-antioxidants/"><strong><span style="color: #993300;">The case against antioxidants</span></strong>,</a> I described how our body’s own Antioxidant Response Element is far more capable and nuanced in dealing with free radical oxidants, than the ingestion of exogenous antioxidant “vitamins” like Vitamins C and E.</p> <p><strong>How do we activate the Phase II enzymes? </strong>The Phase 2 system is not so much “induced” as <a href="http://www.gilbertssyndrome.com/detoxification.php">activated by Phase 1 products and by strengthened by nutrients</a>.  Different foods and nutrients activate different Phase II enzymes:</p> <ul> <li><a href="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-4.jpeg"><img class="alignright size-full wp-image-5255" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-4.jpeg?resize=225%2C225" alt="Unknown-4" width="225" height="225" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-4.jpeg?w=225&ssl=1 225w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-4.jpeg?resize=150%2C150&ssl=1 150w" sizes="(max-width: 225px) 100vw, 225px" data-recalc-dims="1" /></a>Glutathione conjugation: Brassica family foods (cabbage, broccoli, Brussels sprouts); limonene-containing foods (citrus peel, dill weed oil, caraway oil)</li> <li>Amino acid conjugation: Glycine</li> <li>Methylation: Lipotropic nutrients (choline, methionine, betaine, folic acid, vitamin B12)</li> <li>Sulfation: Cysteine, methionine, taurine</li> <li>Glucuronidation: Fish oils, limonene-containing foods</li> </ul> <p>In my earlier post, <a href="//www.tennisbs.com/2011/03/the-case-against-antioxidants/"><span style="color: #993300;"><strong>The case against antioxidants</strong></span>,</a> I provided a more extensive list of phytochemical-rich plant foods, herbs and spices that have been shown to activate the Phase II enzymes, including curcumin, green tea, garlic, rosemary, ginko, bee propilis, and even…coffee!</p> <p><strong>亚搏体育客户端下载 ary hormesis.</strong> Once we understand that the Phase II system is turned on in response to environmental exposure, it becomes logical to ask the question:  Can the char compounds in cooked meat themselves, if consumed in moderation,  actually improve our health by building our tolerance for potential toxins and carcinogens?</p> <p>There is some evidence that this is indeed the case.  For example,<a href="http://www.nature.com/ejcn/journal/v61/n2/full/1602507a.html"> a 2007 study by Hayes</a> in the European Journal of Clinical Nutrition found evidence that for dietary acrylamide as a “hormesis-inducing agent”.  Among the studies cited by Hayes</p> <ul> <li>Mucci (2003) found that that higher levels of acrylamide intake were associated with significant reductions in large bowel, colorectal and kidney cancers</li> <li>Collins (1989) in a study of 9000 workers exposed to acrylamide over 50 years, found a statistically  significant decrease in deaths from all causes</li> </ul> <p>More to the point, there is some evidence that consumption of grilled beef itself activates our endogenous Phase II anti-oxidant enzymes.  In <a href="http://dx.doi.org/10.4236/fns.2013.41013">a 2013 study of grilled beef consumption</a> by 29 healthy non-smoking males, without prior occupational exposure to PAHs, it was found that twice-daily consumption of charcoal-broiled hamburgers resulted in significant increases in serum levels of antioxidant enzymes GOT, GPT and ALP.  Levels of non-enzymatic “sacrificial” antioxidants decreased, but that is not surprising given the “load” put on the detoxification system.</p> <p><strong>The bottom line.</strong>  It’s time to summarize the argument in this blog post:</p> <ol> <li><a href="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-3.jpeg"><img class="alignright size-full wp-image-5253" src="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-3.jpeg?resize=259%2C195" alt="Unknown-3" width="259" height="195" srcset="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-3.jpeg?w=259&ssl=1 259w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/09/Unknown-3.jpeg?resize=150%2C113&ssl=1 150w" sizes="(max-width: 259px) 100vw, 259px" data-recalc-dims="1" /></a>Unlike any other mammal or primate, humans evolved to specialize in eating cooked meats and plants</li> <li>There is no direct evidence that the compounds produced by grilling meat are toxic or carcinogenic to humans.</li> <li>Activating our xenobiotic detoxification system by moderate consumption of grilled meat may actually strengthen our generalized ability to neutralize toxins and carcinogens</li> <li>Therefore, embrace grilled meats — don’t fear them.</li> <li>If you have any remaining qualms, grill in moderation, and eat a side of broccoli or Brussels sprouts with your steak or burger, or mix a little turmeric, rosemary, or garlic into the recipe.</li> </ol> <div>Happy grilling!</div> <div></div> <div>…</div> </div> //www.tennisbs.com/2015/09/is-charred-meat-bad-for-you/feed/ 23 5211 Live longer! //www.tennisbs.com/2015/03/live-longer/ //www.tennisbs.com/2015/03/live-longer/#comments Todd Wed, 01 Apr 2015 05:28:13 +0000 Uncategorized antagonistic pleiotropy anti aging antioxidants Aubrey De Grey autophagy BDNF Bill Gifford Brown-Sequard caloric restriction estrogen exercise Geron growth hormone yabo亚洲 hormone replacement therapy hyperfunction yabo亚洲 James Vaupel Jay Olshansky Leonard Hayflick longevity Mikhail Blagosklonny mitochondria mTOR oxidative stress Ray Walford resveratrol Ron Rosedale selection shadow supplements telormerase testosterone Valter Longo //www.tennisbs.com/?p=5088 So you want to live a long life, or at least age gracefully? Bill Gifford has provided a well-researched and engrossing account of the quest for longevity. In his new book, Spring Chicken, Gifford critically examines the claims of scientists, enthusiasts and hucksters in their attempts to extend life using hormone replacement therapy, telomerase, supplements, drugs, exercise, caloric restriction, intermittent […] <p><a href="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Spring-Chicken.jpg"><img class="alignright size-full wp-image-5091" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Spring-Chicken.jpg?resize=230%2C346" alt="Spring Chicken" width="230" height="346" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Spring-Chicken.jpg?w=230&ssl=1 230w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Spring-Chicken.jpg?resize=100%2C150&ssl=1 100w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Spring-Chicken.jpg?resize=199%2C300&ssl=1 199w" sizes="(max-width: 230px) 100vw, 230px" data-recalc-dims="1" /></a></p> <p>So you want to live a long life, or at least age gracefully?</p> <p>Bill Gifford has provided a well-researched and engrossing account of the quest for longevity. In his new book, <strong><a href="http://www.amazon.com/Spring-Chicken-Young-Forever-Trying/dp/1455527440/ref=sr_1_1?s=books&ie=UTF8&qid=1425874003&sr=1-1&keywords=spring+chicken">Spring Chicken</a>,</strong> Gifford critically examines the claims of scientists, enthusiasts and hucksters in their attempts to extend life using hormone replacement therapy, telomerase, supplements, drugs, exercise, caloric restriction, yabo亚洲 and other practices. Along the way, he visits with a 108-year old investment advisor and a 76-year old female sprinter who can run a 6:58 mile, and he  takes a close look at mice, monkeys and microbes that live much longer than species norms.</p> <p>I found the book hard to put down. That’s not merely because Bill’s hilarious account of my wintry swim with him in the Pacific Ocean appears in Chapter 12–as a bracing illustration of how hormesis builds stress tolerance.  I was captivated by reading of his up-close encounters with a diverse set of gerontologists, centenarians and odd, long-lived creatures such as the naked mole rat. Most interesting of all was his meticulous detective work in probing the major competing theories of aging, leading to some unconventional conclusions about what may or may not actually help prolong life and healthspan.</p> <p><span id="more-5088"></span></p> <p> </p> <p><a href="//www.tennisbs.com/2015/03/spring-chicken/i294588-1-1_gifford/" rel="attachment wp-att-5127"><img class="alignleft size-full wp-image-5127" src="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/I294588-1-1_gifford.jpg?resize=225%2C225" alt="I294588-1-1_gifford" width="225" height="225" srcset="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/I294588-1-1_gifford.jpg?w=225&ssl=1 225w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/I294588-1-1_gifford.jpg?resize=150%2C150&ssl=1 150w" sizes="(max-width: 225px) 100vw, 225px" data-recalc-dims="1" /></a>Spring Chicken, which last month hit Amazon’s top ten bestseller list and was featured in entertaining interviews on <a href="http://www.npr.org/blogs/health/2015/02/26/389261354/from-naked-mole-rats-to-dog-testicles-a-writer-explores-the-longevity-quest">NPR’s Fresh Air</a> and <a href="https://youtu.be/KA4MAcCUtFU">Dr. Oz,</a> stems in part from Gifford’s own personal reflections upon reaching middle age. He was struck by huge disparities in the way his older relatives and even his beloved dogs aged — not merely in the length of their years, but in the duration of their vitality.  As an athlete and writer for fitness and science magazines such as Men’s Health, Outside, Bicycling and Wired, Gifford wanted to  take a much deeper dive into the both the science and popular lore about how to prolong lifespan and health span.</p> <p>Theorizing about longevity has a relatively short history, because until recent times the bigger problem was survival beyond childhood and youth. During the past two centuries, advances in sanitation, nutrition, and public safety (despite what you’d think from watching the news) have enabled an almost linear increase in average lifespan. The question now is what controls the upper limit on the maximum and average length of time humans live.</p> <p><strong>Theories of Aging.  </strong>There are numerous alternative explanations for why we age. Without oversimplifying too much, aging theories can be lumped into three big buckets.  Two of these competing theories have until recently dominated the discussion:  the <em><strong>genetic program theory</strong></em>, and the <em><strong>damage accumulation theory</strong></em>. While each of these two theories has a certain plausibility, Gifford’s book puts them through the ringer and shows where they fall apart. At the end of Spring Chicken, he turns to a third, relatively recent theory of aging that seems quite plausible:  the <em><strong>hyperfunction theory</strong></em> of aging.   This third theory fits quite well with my own thinking about why hormesis is good for you.</p> <p>But let’s start with the two conventional wisdom about what determines lifespan.</p> <p><strong>The genetic program theory.  </strong>There is a lot of evidence to support the idea that aging is an inevitable result of genetic programs.  Every species has its own program, which more or less determines a fixed timetable for development and maximum lifespan, assuming the organism survives premature death by disease or accidents.  The big question is whether or not this programmed timetable can be altered.   On this question, gerontologists divide into two camps:  the pessimists and the optimists.</p> <p><strong>The genetic program theory, version 1:  the pessimists.</strong> A leading spokesman for the pessimists is Jay Olshansky, a gerontologist and demographer from the University of Illinois at Chicago. Olshansky believes that the maximum human lifespan is roughly the same as that lived by Jean Calmet, the current record-holder at 122 years.  He thinks that the maximum average lifespan of population won’t go higher than where it is today — about 85 years.  A healthy lifestyle, supplements and the conquest of disease won’t do much to change that; in fact, average lifespans may actually start to decrease.  Pessimists like Olshansky point to realities such as the Hayflick limit — the discovery by biologist Leonard Hayflick that mammalian cell lines aren’t immortal, but can only divide about 50 times before they inevitably die.  This appears to be an unavoidable consequence of a genetic “clock” controlled by telomeres — regions of chromosomes that become progressively shorter with each cell division cycle.</p> <p><strong>The selection shadow.</strong> The genetic pessimists also find support in an evolutionary principle called “the selection shadow”.  Natural selection favors genes that enhance the survival of individuals through the age of reproduction.  After that age, there is no selective pressure on the genome to promote a long and healthy life.  In short, evolution doesn’t care about longevity of the body (a.k.a. the “disposable soma”) but only the passing of the germ line to the next generation.</p> <p><a href="//www.tennisbs.com/2015/03/spring-chicken/unknown-5-2/" rel="attachment wp-att-5139"><img class="alignright size-full wp-image-5139" src="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-5.jpeg?resize=199%2C253" alt="Unknown-5" width="199" height="253" srcset="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-5.jpeg?w=199&ssl=1 199w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-5.jpeg?resize=118%2C150&ssl=1 118w" sizes="(max-width: 199px) 100vw, 199px" data-recalc-dims="1" /></a>A corollary of the selection shadow is a phenomenon called <em><strong>antagonistic pleiotropy</strong></em>:  traits that are adaptive for reproductive success in youth have secondary effects that are frequently detrimental after the age of reproduction.  For example, the same genes  that produce high levels of dihydrotestosterone and prostaglandin D2–thereby spawning robust hair growth in young men, a visual marker of health and sexual attractiveness in youth–eventually produce the secondary effect of reduced hair follicle size and male pattern baldness with progressive age.  (Presumably, these genes had greater selective value when the typical age of reproduction was younger).  Other examples of antagonistic pleiotropy include diseases such as:</p> <ul> <li><em><strong>Huntington’s disease</strong></em> – resulting from genes that <a href="http://www.sciencedaily.com/releases/2007/09/070925130029.htm">increase fertility and immune health in childbearing years</a>, but manifesting as a crippling form of dementia in middle age</li> <li><em><strong>Hemochromatosis</strong></em> – high blood iron levels that are protective against plague, but become ulimately inflammatory and toxic in midlife and old age</li> </ul> <p>It’s likely that hardening of the arteries, skin wrinkling and other aging processes result from genetically controlled development programs that are beneficial in the bloom of youth but detrimental after the childbearing years.</p> <p>There is a flip side to antagonistic pleiotropy:  organisms with mutations that promote longevity tend to reproduce later, so they are out-competed and get bred out by younger, more prolific reproducers. This has been shown by Gordon Lithglow in the <em>C. elegans</em> worm.  Worms mutated to knock out the daf-2 gene lived twice as long as normal worms. But when these worms were mixed with normal worms, they reproduced more slowly and the long-lived worms were bred out of the population after only four generations!  In humans too,  such “longevity genes” tend to get bred out of populations:  A study of centenarian Ashkenazi Jews found that they tended to have fewer children and had them later in life, even before the age of birth control.  So living longer seems to be advantageous for the individual, but not for the species.</p> <p><strong>The genetic program theory, version 2: the optimists.</strong> Not all the genetic program theorists are pessimists.  James Vaupel, Director of the Max Planck Institute for Demographic Research, is impressed by the finding that there has been a steady, almost linear increase in lifespan over the past two centuries. Since 1840, average lifespan has increased at a very steady rate of about 2.4 years per decade.  Up until about 1950, this was mainly a result of eliminating the causes of death in childhood and youth — childbirth mortality, infectious disease, malnutrition.  Since 1950, lifespan has increased mainly by attacking “diseases of old age” – cancer, cardiovascular disease and the like.</p> <p>Some of the “optimists”, like Aubrey De Grey, believe that there is no fixed upper limit on age.  He’s a true zealot for the cause of life extension, once claiming on the program <a href="http://www.cbsnews.com/news/the-quest-for-immortality/">60 Minutes</a> that some people now alive would live to be 1000 years old, outpacing Methuselah of the Bible.  Until now, longevity has been increased slowly by tackling one disease at a time.  But is aging the result of old-age diseases like cancer, diabetes, cardiovascular disease and dementia?  Or is there some fundamental “root cause” driver of aging that happens to result in these diseases?  De Grey wants to identify and attack the root causes of aging.</p> <p>The burgeoning field of “anti-aging medicine” is based on the idea that we can slow the pace of the genetic program by compensating for deficiencies that develop over time in the inputs. Recently, the <a href="http://paloaltoprize.com">Palo Alto Longevity Prize</a> has been organized as a “life science competition dedicated to ending aging”.  Two  $500,000 prizes have been offered to teams that can increase lifespan by 50% relative to a control mammal, or restore the HRV of an aging mammal to that of a youth.</p> <p>Perhaps the genetic program can be “hacked” — either by changing the inputs or by modifying the program itself.  What are the inputs?  Primarily hormones and supplements.  Presumably our developmental genetic programs “run down” as we age because hormone and nutrient levels run down. To extend life, we need to replenish, restore, and re-energize.</p> <p><strong>Restoring hormones.</strong> Some of the more amusing stories in Spring Chicken concern the history of hormone replacement therapies.  Gifford traces this back to nineteenth-century experiments by Charles Edouard Brown-Séquard, who injected himself, then others, with extracts from crushed testicles from dogs and guinea pigs.  He experience renewed vitality and commercialized his testosterone-rich concotion as “Séquard’s Elixir of Life.”   The fad died along with Brown-Séquard five years later. While the results were variable and short-lived, the experience of restored stamina led ultimately to what continues today as a hopeful set of treatments to extend life and physical prowess using more standardized infusions of testosterone, estrogen, growth hormone, and other steroid hormones.</p> <p><a href="//www.tennisbs.com/2015/03/spring-chicken/unknown-3-5/" rel="attachment wp-att-5131"><img class="alignleft wp-image-5131" src="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-3.jpeg?resize=170%2C217" alt="Unknown-3" width="170" height="217" srcset="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-3.jpeg?w=199&ssl=1 199w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-3.jpeg?resize=118%2C150&ssl=1 118w" sizes="(max-width: 170px) 100vw, 170px" data-recalc-dims="1" /></a>Hormone replacement therapy (HRT) was a mainstream therapy for decades until 2002, when the Women’s Health Initiative study found strong evidence of increased breast cancer among women using estrogen supplements.   At that point, some explained this negative result as a consequence of using unnatural, synthetic forms of estrogen, and failing to balance the estrogen with progesterone and testosterone.  Suzanne Somers and others now advocate the use of “bioidenticals”, which presumably restore the natural hormones in proper balance.  However, studies even with bioidenticals raise safety concerns for use beyond about 3-5 years, after which elevated levels of estrogen and other hormones can elevate the risk of atherosclerosis, cancer or dementia.  Similarly, extended use of testosterone and human growth hormone has been linked to increased risk of cardiovascular disease, stroke and death.   It seems that hormones which help promote growth and sexual maturity in youth can indeed have negative consequences when introduced later in the genetic program,</p> <p><a href="//www.tennisbs.com/2015/03/spring-chicken/great_dane_chihuahua/" rel="attachment wp-att-5130"><img class="alignright wp-image-5130" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/great_dane_chihuahua.jpg?resize=320%2C193" alt="great_dane_chihuahua" width="320" height="193" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/great_dane_chihuahua.jpg?w=397&ssl=1 397w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/great_dane_chihuahua.jpg?resize=150%2C91&ssl=1 150w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/great_dane_chihuahua.jpg?resize=300%2C181&ssl=1 300w" sizes="(max-width: 320px) 100vw, 320px" data-recalc-dims="1" /></a>A deeper challenge to the rationale for hormone replacement therapy comes from research showing that a “deficiency” of hormones is no impediment to a long life, but may actually prolong life.  The longest living lab mice actually have <em><strong>no</strong></em> growth hormone receptors. Mice that are genetically altered to stop producing growth hormone in fact live twice as long as normal mice. Chihuahuas lack growth hormone but <a href="http://www.chihuahuawardrobe.com/chihuahua-lifespan-average-life-expectancy-of-the-chihuahua/">outlive most larger dogs</a>.   It’s not just smaller animals that tend to live longer.  The Larone “little people” of the Andes Mountains have a rare genetic mutation, similar to that of the dwarf mice and Chihuahaus, resulting in lack of growth hormone receptors, short stature and old age.  They appear to be resistant to cancer and diabetes. As Gifford reports, “They eat whatever the hell they want, they smoke, and they drink, and they still live pretty long.”</p> <p>Mechanistic studies confirm that growth hormone stimulates IGF-1, the growth factor that stimulates cell growth and division and spurs associated aging processes.   So maybe hormone supplementation is not the panacea proffered by some in the anti-aging medicine field.</p> <p><strong>Engineering longevity? </strong> Aubrey de Grey has outlined a program he terms SENS: Strategies for Engineering Negligible Senescence.  Some of the SENS strategies involve somehow engineering the genome to reduce — or eliminate — the deleterious cellular processes that shorten life.  This seems to me to be a rather utopian idea, harboring the potential for unintended consequences.  Since genes are pleiotropic (they have multiple different regulatory functions individually and in concert), an innocent genetic “edit”–intended to confer a certain identifiable benefit– could risk causing deleterious secondary consequences, in respects that may not be immediately apparent.</p> <p><a href="//www.tennisbs.com/2015/03/spring-chicken/unknown-4-5/" rel="attachment wp-att-5132"><img class="alignleft wp-image-5132 size-full" src="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-4.jpeg?resize=259%2C194" alt="Unknown-4" width="259" height="194" srcset="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-4.jpeg?w=259&ssl=1 259w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-4.jpeg?resize=150%2C112&ssl=1 150w" sizes="(max-width: 259px) 100vw, 259px" data-recalc-dims="1" /></a>Genetic studies found associations between shorter telomeres  (the “end caps” on certain chromosomes) and increased incidence of diseases of aging — such as cancer, cardiovascular disease and dementia.  At the same time, athletes and certain long-lived species exhibit well preserved telomeres.  So one of the more reasonable ideas for revamping the genetic program is not to monkey with the genetic code, but rather to slow the biological clock by reducing the rate at which telomeres erode. The discovery in 1984 of telomerase — the enzyme that repairs and restores telomeres – created much excitement within the anti-aging movement.  Companies like <a href="http://www.geron.com">Geron</a> were spawned to commercialize potential clinical uses for telomerase.</p> <p>However, Gifford raises an excellent question about the connection between telomeres and aging:  Do shorter telomeres <strong><em>cause</em></strong> aging or are they <strong><em>a result of</em></strong> aging processes?  He cites a study of 4500 people which found that there is no link between shorter telomeres and mortality, after controlling for life-shortening behaviors like smoking and alcohol abuse.  Furthermore, there is evidence that activating telomerase might cause cancer. Cancer cells have much more telomerase then normal cells. And some animals with very long telomeres and lots of telomerase actually live a very short time, such as laboratory mice.</p> <p>So much for the genetic programming theory.  Let’s now turn to the second major theory of aging.</p> <p><strong>The damage accumulation theory.  </strong>Another name for this theory is the “free-radical theory of aging”.  If you are one who takes vitamin or antioxidant supplements, you’ve no doubt been influenced by the theory that aging is caused by–or at least accelerated by– “oxidative stress”.  Oxidative stress is what happens when free radicals and reactive oxygen species (ROS) react with proteins, lipids, DNA and other biological molecules to cause molecular damage within the cell. Over time, this damage accumulates in tissues and organs such as skin, arteries, neurons, eyes — and especially in the mitochondria, the energy powerhouse inside each cell.  To some extent, cellular repair processes can partially reverse this damage. But according to the damage accumulation theory, at some point the damage starts to outstrip the repair capacity our cells — and the consequence is wrinkled skin, grey hair, hardened arteries, atrophied muscles, tangled neurons, and impaired immune defenses against infections and cancer.  In short — oxidative stress is proposed as the root cause of aging.</p> <p>Hence the popular enthusiasm for antioxidants such as vitamins C and E, Co-Q10, glutathione and the like.  You can’t go into a pharmacy these days without seeing racks of these supplements.  Some people pop more than a dozen of these pills a day.</p> <p>Spring Chicken does a beautiful job of skewering the damage accumulation theory, serving up one challenging counterexample after another.  I’ll cite just three that should give you pause:</p> <ul> <li><strong><em><a href="//www.tennisbs.com/2015/03/spring-chicken/unknown-7-2/" rel="attachment wp-att-5149"><img class="alignright size-full wp-image-5149" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-7.jpeg?resize=259%2C194" alt="Unknown-7" width="259" height="194" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-7.jpeg?w=259&ssl=1 259w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-7.jpeg?resize=150%2C112&ssl=1 150w" sizes="(max-width: 259px) 100vw, 259px" data-recalc-dims="1" /></a></em>The failure of antioxidant supplements to extend lifespan.</strong> If oxidative stress is the enemy of youthfulness, then taking antioxidant supplements should neutralize free radicals and ROS, inhibit the damage and extend lifespan.  But study after study in animals and humans has failed to show any evidence that it does so.  Studies of  vitamin C and selenium show no conclusive effect on longevity.   A study of more than 230,000 people found that supplementation with vitamin A, vitamin E and beta-carotene actually <em><strong>increased</strong></em> mortality risk.</li> <li><strong>The essential biological function of oxidative stress.</strong>  Exercise is known to immediately increase oxidative stress. An exercise study by Michael Ristow asked subjects to work out 5 days a week, and biopsied their muscles after the workouts. During the study,  half the subjects ingested high levels of vitamins C and E, while the others took placebo pills.  Both groups showed high levels of oxidative stress in their muscles after the workouts.  But those who took the antioxidants failed to show the training benefits achieved by those who took no antioxidants.  As I noted in my article, <span style="color: #993300;"><strong><a style="color: #993300;" href="//www.tennisbs.com/2011/03/the-case-against-antioxidants/">The case against antioxidants</a></strong></span>, this is actually no mystery.  While excessive and chronic oxidative stress may be detrimental, short term oxidative stress during exercise is actually a good thing; it is the basis for cell signaling between nerves and muscles.  Shutting it down can impair performance.  In addition, oxidative stress activates the Nrf2 pathway, upregulating production of the body’s own endogenous antioxidants, such as superoxide dismutase and glutathione reductase.  These endogenous antioxidants are turned on in the right tissues at the right time, for only as long as needed.  Unfortunately, consumption of high levels of antioxidant supplements shuts down the Nrf2 pathway and production of endogenous antioxidants and key repair enzymes.  Paradoxically, supplementing with antioxidants can increase vulnerability to the effects of oxidative stress.</li> <li><em><strong><a href="//www.tennisbs.com/2015/03/spring-chicken/unknown-6-2/" rel="attachment wp-att-5148"><img class="alignright size-full wp-image-5148" src="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-6.jpeg?resize=303%2C166" alt="Unknown-6" width="303" height="166" srcset="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-6.jpeg?w=303&ssl=1 303w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-6.jpeg?resize=150%2C82&ssl=1 150w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-6.jpeg?resize=300%2C164&ssl=1 300w" sizes="(max-width: 303px) 100vw, 303px" data-recalc-dims="1" /></a></strong></em><strong>The existence of animals that live long despite high oxidative damage.</strong> The naked mole rat is perhaps the most vivid refutation of the damage accumulation theory.  This small burrowing rodent can live about 30 years — about 6 times as long as the longest-lived known lab rat.  Naked mole rats must have very little oxidative damage in their bodies, right?  Wrong. Their tissues and organs are wracked with very high levels of oxidative “damage”.  And when raised in captivity, where they are exposed to higher concentrations of oxygen and even more oxidative stress than they would see in their natural life, they live just as long.  In fact, naked mole rats seem to benefit from a very robust stress response — hormesis — that helps them outlive their more ordinary rodent cousins.  Their prodigious hormetic ability appears to lie in a high functioning proteasome, the cellular system that removes and repairs damaged parts.  When lab rats die of old age, it’s usually cancer that gets them. The naked mole rat just doesn’t get cancer.  And it’s not alone; there are many other long lived species that exemplify old age in the face of extreme accumulation of damage.</li> </ul> <p>What we can we take away from the failures of the genetic program theory and the damage accumulation theory to explain aging and extend life?  I think Bill Gifford summarizes the complexity of the situation most aptly:</p> <blockquote><p>What is clear is that aging is a lot more tricky than most people realize–and that simply putting something back, like growth hormone or whatever supplement happens to be trendy at the moment, isn’t going to solve the problem… “Imagine you have a symphony written by Mozart,” says Valter Longo, a professor of biology at USC and a leading researcher on aging. “Taking growth hormone or a supplement or whatever is like going to the cello player and saying, ‘Can you just make it a lot louder?’ Chances are, it will screw things up. (SC, p. 61).</p></blockquote> <p><strong>The hyperfunction theory.  </strong>What if aging is a result not of <em><strong>deficient inputs</strong></em> to the developmental program, or <strong><em>external insults</em></strong> to the program — but rather a result of the program <strong><em>going into overdrive, becoming a “runaway” program?  </em></strong>Overactivity rather than underactivity or underprotection.  That may at first sound like a bizarrely improbable and iconoclastic theory.  But the hyperfunction theory of aging is gaining credence as a plausible explanation with some surprising and hopeful consequences.</p> <p>Major proponents of the hyperfunction theory include Mikhail Blagosklonny, David Gems, Yila de la Guardia, Linda Partridge and Valter Longo. They agree with the genetic program theory that life is governed by a “program”, but it is a developmental program, not specifically an aging program. According to <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615154/">Blagosklonny</a>, aging can be viewed a “a quasi-program, a useless and unintentional continuation (or run on) of developmental programs.”</p> <p><a href="//www.tennisbs.com/2015/03/spring-chicken/images-7/" rel="attachment wp-att-5160"><img class="alignright size-full wp-image-5160" src="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/images.jpeg?resize=300%2C168" alt="images" width="300" height="168" srcset="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/images.jpeg?w=300&ssl=1 300w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/images.jpeg?resize=150%2C84&ssl=1 150w" sizes="(max-width: 300px) 100vw, 300px" data-recalc-dims="1" /></a>The hyperfunction theory holds that the diseases of aging come about from growth signaling pathways “running on inertia”, resulting in over-stimulation of normal cell functions. Classic examples of hyperfunction or overdrive can be seen in the overactive inflammatory processes of  cardiovascular plaque formation, platelet aggregation in stroke, rampant cell division of cancer, unchecked lipogenesis in obesity, or beta cell burnout and runaway glycogenesis in diabetes.  Hyperfunction ultimately leads to a loss of homeostasis, marked by elevated blood pressure and blood glucose, leading to organ damage.</p> <p>At the very root of these runaway processes is a central regulatory pathway known as mTOR — short for “mammalian target of rapamycin”.  (In his book, Gifford uses the less common shorter acronym TOR, as this same growth pathway is found even in yeast and worms). In normal developmental, the mTOR pathway drives the growth processes of youth, to help ensure the organism reaches the age of reproduction in good health.  But when the mTOR-driven growth processes are sustained into middle age, running at full throttle and beyond their usefulness, these processes can backfire.  Seen in this light, what we referred to earlier as “antagonistic pleitropy” is not an <em><strong>accidental</strong> </em>secondary result of early development functions, but a predictable consequence of “too much for too long”.  For example, in young males, mTOR induces the growth hormones and sex hormones that drive normal development and enable useful primary and secondary sexual characteristics;  but beyond the age of sexual maturity, the continued secretion of elevated testosterone levels can lead to the “hyperfunction” of male pattern baldness.</p> <p>How do the hyperfunction theorists view oxidative damage?  According to Blagosklonny, oxidative damage is not a cause of aging, but rather  a consequence — collateral damage from  the mTOR-driven inflammatory processes underlying aging processes like cancer, atherosclerosis, osteoporosis, diabetes, hypertension, obesity and dementia.</p> <p>If you accept the hyperfunction theory, then life and health span can be lengthened by “turning down the throttle” as we move past youth into middle age, calming the mTOR pathway.  This strategy can take be executed using a variety of tactics:</p> <ul> <li><strong>Drug compounds</strong> such as metformin or rapamycin, which directly inhibit the mTOR pathway, can help rein in excessive cellular function and blocking inflammatory pathways.  Both compounds have shown efficacy in treating diabetes and hypertension. Blocking the TOR pathway in yeast triples lifespan.  In mice, rapamycin has reduced cancer incidence, increased tendon elasticity, and dramatically extended lifespan.  Could rapamycin be useful in extending human lifespan. Perhaps, though one downside is that it sometimes suppresses immune function.  The is also some evidence that natural products such as <a href="http://www.ncbi.nlm.nih.gov/pubmed/20812900">caffeine, green tea, curcumin and resveratrol</a> act as mTOR inhibitors.</li> <li><strong>亚搏体育客户端下载 ary restriction</strong> is a powerful way to inhibit mTOR.  Valter Longo observes that diets high carbohydrates and proteins they increase levels of nutrient sensors like insulin and mTOR, activating growth inducers such as leptin, IGF-1 and growth hormone.  These hormones and inducers are are beneficial in the short term, but if overextended they promote obesity and the associated metabolic syndrome of diabetes, hypertension, cardiovascular disease and dementia.  Longo points to long-lived residents of Calabria, Italy, like 109-year old Salvatore Caruso, who eat a diet low in both carbohydrates and protein.  Ron Rosedale similarly emphasizes the value of restricting carbs and protein in <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831640/">suppressing mTOR in order to extend lifespan</a>. Rosedale further links mTOR to the thyroid’s control of metabolic rate.   In this context, I find very illuminating his analogy comparing mTOR and thyroid control of resting metabolism with <a href="http://drrosedale.com/blog/2012/10/31/thermogenesis-not-so-good-for-health-ron-rosedale/#axzz3UOGu7NWq">the idle of an automobile</a>:<br /> <blockquote><p><a href="//www.tennisbs.com/2015/03/spring-chicken/unknown-9-2/" rel="attachment wp-att-5161"><img class="alignleft wp-image-5161 size-thumbnail" src="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-9.jpeg?resize=150%2C137" alt="Unknown-9" width="150" height="137" srcset="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-9.jpeg?resize=150%2C137&ssl=1 150w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-9.jpeg?w=235&ssl=1 235w" sizes="(max-width: 150px) 100vw, 150px" data-recalc-dims="1" /></a>In calorie-restricted animals, researchers generally see a lower free T3 [thyroid hormones].  They also see lower T3 in centenarians, people who live past 100. When you see a lower free T3, it’s really indicative of kind of a longevity phenotype. It’s indicative of what you might even call, non-hibernating hibernation. And one clue that this lower T3 is healthy is that people who have it generally report that they function better.  If it happens to you, on a low-carb diet that you’ve become adapted to over time, you’re not weak. You generally have more energy. Having your T3 level go lower, in a healthy way, is like being able to turn down the idle of a car when it’s tuned properly, so that at rest it doesn’t have to waste as much energy.  In an efficiently running car, the resting “metabolism” of the car is lower.  And if you want to get power from that car, if you want to accelerate, that’s better too.  When a car is well tuned, it allows for a lower idle speed, and it will actually accelerate faster, and the engine itself certainly will have a much longer lifespan. It’s functioning better.</p></blockquote> </li> </ul> <ul> <li><strong>Intermittent fasting</strong> is perhaps the single most effective and practical way to turn down the mTOR pathway and the ensuing growth cascade of hormones like insulin and IGF-1, and associated pro-inflammatory cytokines like interleuken-6. Intermittent fasting– or IF as it’s popularly called — has been shown to induce autophagy, a cellular “house cleaning” process that efficiently removes glycated proteins, damaged nucleic acids and other cellular “junk” when one abstains from food for about 12-18 hours.  <a href="http://www.greenmedinfo.com/blog/skip-meals-live-longer-and-lose-weight">University of Florida</a> researchers recently found that IF boosts expression of the longevity-promoting SIRT3 protein (although taking vitamin C and E supplements cancels out this benefit, apparently by neutralizing the mild oxidative stress).   IF has particular benefits for the brain.  Not only does the ensuing autophagy facilitate removal of damaged proteins and lipids that accumulated intracellularly, but it boosts levels of brain-derived neurotrophic factor (BDNF) that stimulates neurogenesis and help <a href="http://www.ncbi.nlm.nih.gov/pubmed/16176349">regenerate tau protein that becomes phosphorylated in Alzheimer’s disease</a>. Gifford notes that Mark Mattson and others have shown that these benefits of IF don’t require any <strong><em>net</em></strong> calorie restriction, but derive only from the pattern of allowing adequate breaks in the pace of food intake.  This fact impressed Valter Longo, who was rightly horrified by the negative health consequences of more extreme calorie restriction, such as that practiced by Ray Walford of Biosphere fame.  In his own research,  Longo found that introducing a period of IF prior to chemotherapy increased the effectiveness and decreased the side effects in both mice and human trials. He theorizes that switching normal cells to a “low mTOR” state is protective, while the same low mTOR state is highly stressful to fast growth-oriented cancer cells.</li> <li><strong>Exercise</strong> is also a highly effective way to keep mTOR in check and maintain mitochondrial function.  Gifford notes the work of Mark Tarnopolsky of McMaster University in showing that regular exercise activated molecular processes that repaired defective mitochondria DNA in lab mice.  As already noted, exercise induces short term oxidative stress which paradoxically improves stress resistance. Studies by <a href="http://www.sciencedirect.com/science/article/pii/S2095254613000288">Bo et al</a> eludicate the underlying mechanism::</li> </ul> <blockquote> <p style="padding-left: 30px;">[O]ur data suggest that regular exercise training stimulates mitochondrial biogenesis, a rejuvenation of the mitochondrial network via fission and fusion, and an improved efficiency of mitochondrial energy transfer….[T]he accumulation of oxidative damage can be decreased either by lowering the generation of ROS (caloric restriction) or by regular exposure to a small amount of ROS (such as mild exercise) that could result in slight oxidative damage, which then leads to up-regulation of antioxidant systems and amelioration of mitochondrial remodeling.</p> </blockquote> <p><strong>yabo亚洲 and stress resistance in aging.  </strong>Towards the end of his book, Gifford muses that there is no real “secret” to aging:</p> <p>“<strong><em>Use it or lose it</em></strong> may be the best we can do for now”.</p> <p>I think that the hormesis, the stress response, is the best explanation for the effectiveness of  “use it or lose it” in extending life and healthspan. The hyperfunction theory provides a plausible framework to explain the anti-aging benefits of many types of hormesis, including calorie restriction, protein restriction, and yabo亚洲 .</p> <p>Advocates of a “paleo” diet and lifestyle are fond of looking to evolution as a guide for maximizing health and longevity.  But, as Ron Rosedale points out, <a href="https://www.youtube.com/watch?v=HhH3mHdc4g0">evolution doesn’t care about you</a> after you reach the age of reproduction and a bit of child rearing, so <a href="https://www.youtube.com/watch?v=LvTE--5w808">the yardstick of evolution isn’t all that useful as a guide for living to a ripe old age</a>. We need to use science to hack the “unnatural” post-reproductive phase of  genome expression.</p> <p>Evolution selected for the mTOR pathway to channel energy towards reaching sexual maturity and passing along the genes to the next generation.  Eat a lot of protein and carbs in your youth and you’ll grow big and strong and optimize your fertility. But if the hyperfunction theorists are right, that’s not a good plan for living a long and healthy life, because those very growth processes lead to the diseases of aging unless tightly reined in as we get older. Life is loosely guided by a program that is highly “plastic” or adaptable, a program that responds to stimuli. As such, the “life program” for mammals like ourselves can be divided into two phases: the pre-reproductive and post-reproductive phases.  In the pre-reproductive phase, it is indeed beneficial to stimulate the growth and reproduction programs, to gain mass, strength, immunity and fertility.  That’s important.  Undernutrition during this phase can be a liability in reaching maturity. During the post-reproductive phase of the “program”, however, the game changes. Prolonging the stimulation of growth can lead to the conditions that we think of as aging:  heart disease, stroke, hypertension, diabetes, cancer, dementia. So during this second phase of life, in the selection shadow, it’s a good idea to pull back in order to avoid the pitfalls of hyperfunction.</p> <p><a href="//www.tennisbs.com/2015/03/spring-chicken/unknown-10-2/" rel="attachment wp-att-5162"><img class="alignright size-full wp-image-5162" src="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-10.jpeg?resize=275%2C183" alt="Unknown-10" width="275" height="183" srcset="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-10.jpeg?w=275&ssl=1 275w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2015/03/Unknown-10.jpeg?resize=150%2C100&ssl=1 150w" sizes="(max-width: 275px) 100vw, 275px" data-recalc-dims="1" /></a>But reining in the growth programs is not enough, in my view.  It’s especially important during this second phase of life — middle age and old age, to also keep your defense and repair programs humming, because you’ll find that they come in handy.  Strong muscles and bones and a well-tuned brain are an essential foundation for thriving in old age. And that’s where hormesis comes in. By activating our stress responses (within reason), our metabolisms are forced to channel energy way from “growth and reproduction” programs to support “defense and repair” programs.  This goes well beyond merely manipulating diet and energy status to lower the mTOR pathway.  We need stress to thrive as we age! Intense exercise and cold exposure can be effective in stimulating the activation of defense and repair pathways. Those essentials are nurtured by activating the hormesis programs, by means of nutrient limitation, judicious intake of “hormetins” like caffeine, green tea, curcumin and plant phytochemicals, and routine exposure to environmental stressors like vigorous exercise, exposure to cold and heat, and mental challenge.</p> <p>The hormesis programs provide what it takes to keep us sharp.  They represent the physiological basis for Bill Gifford’s prescription to “use it or lose it”.</p> <p><a href="http://www.amazon.com/Spring-Chicken-Young-Forever-Trying/dp/1455527440">Spring Chicken</a> does a nice job of deflating the population misconception that the secret of a long life is a simple matter restoring vitality by injecting some magic hormone, or trying to dodge the onslaught of oxidative stress by gulping fistfuls of antioxidants. Perhaps drinking coffee and supplementing with metformin will help a little.  But if you want to live a long and graceful life, it’s probably more important to moderate your eating, stay physically active and continually challenge yourself.</p> //www.tennisbs.com/2015/03/live-longer/feed/ 22 5088 Is it dangerous to skip breakfast? //www.tennisbs.com/2014/12/is-it-dangerous-to-skip-breakfast/ //www.tennisbs.com/2014/12/is-it-dangerous-to-skip-breakfast/#comments Todd Mon, 08 Dec 2014 08:37:39 +0000 亚搏体育客户端下载 Health yabo亚洲 blood glucose calorie restriction cancer cardiovascular disease cortisol dementia dopamine hormone balance hunger insulin sensitivity yabo亚洲 meal frequency obesity //www.tennisbs.com/?p=4764 There is increasing evidence from recent human and animal studies that yabo亚洲 — refraining from food or caloric beverages for at least 12 hours a day, several days a week — reduces the risks of cardiovascular disease, dementia and cancer.  Those benefits are well-documented in the hyperlinked articles, so I won’t repeat them here.  Yet many nutritionists hold that […] <p><a href="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2014/06/empty_plate.jpg"><img class="alignright wp-image-4842" src="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2014/06/empty_plate.jpg?resize=238%2C221" alt="empty_plate" width="238" height="221" srcset="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2014/06/empty_plate.jpg?w=285&ssl=1 285w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2014/06/empty_plate.jpg?resize=150%2C139&ssl=1 150w" sizes="(max-width: 238px) 100vw, 238px" data-recalc-dims="1" /></a>There is increasing evidence from recent human and animal studies that yabo亚洲 — refraining from food or caloric beverages for at least 12 hours a day, several days a week — reduces the risks of <a href="http://well.blogs.nytimes.com/2011/04/04/regular-fasting-may-boost-heart-health/?_r=1">cardiovascular disease</a>, <a href="http://www.scientificamerican.com/article/new-year-new-understandin/">dementia</a> and <a href="http://naturalmedicinejournal.com/journal/2013-01/caloric-restriction-and-fasting-disease-prevention-and-treatment">cancer</a>.  Those benefits are well-documented in the hyperlinked articles, so I won’t repeat them here.  Yet many nutritionists hold that skipping breakfast or other meals and snacks can lead to weight gain and metabolic imbalance.  Several recent articles have suggested that IF and breakfast skipping is a particularly bad idea for women. Much to my chagrin, this view been even embraced recently by a number of ‘Paleo’ advocates whom I respect, such as <a href="http://chriskresser.com/to-intermittent-fast-or-not-to-fast-that-is-the-question">Chris Kresser</a> and <a href="http://www.marksdailyapple.com/women-and-intermittent-fasting/#axzz3LA1HvaXR">Mark Sisson</a>.</p> <p>In this post I’d like to address three main objections that have been raised against skipping breakfast and other forms of yabo亚洲 :</p> <ol> <li>It spurs hunger cravings, leading to compensatory overeating and obesity</li> <li>It causes cardiovascular disease and metabolic dysregulation of blood glucose and hormone levels</li> <li>It’s bad for women, leading to hormone imbalance, disrupted menstrual cycle, and heightened stress response</li> </ol> <p>I believe these concerns with breakfast skipping are overblown, based on an incorrect interpretation of a few animal and human studies, and flawed personal implementation.  To the contrary, adaptation to meal skipping can actually <em><strong>help</strong></em> boost stress tolerance and improve blood sugar control. If practiced correctly, yabo亚洲 (IF) can actually be a powerful tool to overcome hypoglycemic symptoms, and regain control over a harried lifestyle.   And it can be particularly useful for women who are struggling with cravings, weight management and stress management.</p> <p>Opposition to yabo亚洲 arises from both published research and anecdotal reports.  I’d like to address both in this post.  I’ll first point out some significant flaws in the interpretation of several recent studies purporting to show negative effects of reduced meal frequency on women and other groups.  And I’ll end by pointing out how to avoid common mistakes made by many who try yabo亚洲 find it to be unpleasant and unsustainable.</p> <p>Approached correctly, IF can provide major health benefits for most us.</p> <p><span id="more-4764"></span></p> <p>Let’s dig in to the arguments that have been made in support of these three myths about breakfast skipping and yabo亚洲 :</p> <p><strong>Myth 1: It spurs hunger cravings, leading to compensatory overeating and obesity.</strong>  A number of observational studies report a correlation between breakfast skipping and obesity.  For example, a <a href="http://www.ncbi.nlm.nih.gov/pubmed/20497776">2010 study of 9659 teenagers</a> found that self-reporting breakfast skippers had higher BMI, and waist size than those who ate breakfast.</p> <p><a href="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown.jpeg"><img class="alignleft wp-image-5015" src="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown.jpeg?resize=348%2C170" alt="Unknown" width="348" height="170" srcset="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown.jpeg?resize=300%2C147&ssl=1 300w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown.jpeg?resize=150%2C73&ssl=1 150w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown.jpeg?w=320&ssl=1 320w" sizes="(max-width: 348px) 100vw, 348px" data-recalc-dims="1" /></a>Some have attempted to explain this association in terms of overcompensation for hunger.  The idea is that  skipping the first meal of the day is counterproductive because it backfires, stoking hunger and leading to a high net intake of calories later in the day.  This view seems to find support in <a href="http://www.nutritionj.com/content/13/1/80">a 2014 CDC study of eating behavior among overweight young adult women</a>.  The participants were screened to include only those who already habitually skipped breakfast and were overweight (BMI 25-35 kg/m2).  The study measured dopamine levels (using homovanillan, a dopamine metabolite) and subjective cravings in response to different breakfasts, or skipping breakfast.   It was found that, compared to eating breakfast, skipping breakfast resulted in a gradual increase in cravings and lower dopamine levels over a 4-hour morning sampling period.</p> <p>According to <a href="http://munews.missouri.edu/news-releases/2014/1015-eating-breakfast-increases-brain-chemical-involved-in-regulating-food-intake-and-cravings-mu-researchers-find/">Heather Leidy</a>, the lead author,</p> <blockquote><p>Our research showed that people experience a dramatic decline in cravings for sweet foods <span id="IL_AD5" class="IL_AD">when they</span> eat breakfast. However, breakfasts that are <span id="IL_AD1" class="IL_AD">high in protein</span> also reduced cravings for savory – or high-fat – foods. On the other hand, if breakfast is skipped, these cravings continue to rise throughout the day….It used to be that nearly 100 percent of American adults, kids and teens were eating breakfast, but over the last 50 years, we have seen a decrease in eating frequency and an increase in obesity.</p></blockquote> <p>It’s not really surprising that eating breakfast would reduce hunger and increase dopamine  levels relative to not eating breakfast, is it?  The more important question is whether skipping breakfast and the increased mid-day appetite leads to obesity or long term weight gain via compensatory eating later in the day.  The CDC study didn’t specifically address that question.  It could not answer the question of progression to obesity, because it started out with <strong><em>a pre-selected group of already overweight teenagers who were already breakfast skippers</em></strong>.</p> <p>So who knows what led to their <em><strong>initial</strong> </em>weight gain prior to the study. We don’t know whether their breakfast skipping was the <strong><em>cause</em></strong> of their high BMI.  It is entirely possible that their breakfast skipping was a <em><strong>consequence</strong> </em>of their BMI or something related to it.   In fact, the authors of the study end by acknowledging these uncertainties:</p> <blockquote><p>Specifically, reduced breakfast frequency (i.e., breakfast skipping) is inversely associated with increased BMI, weight gain, and obesity in young people.  However, due to the lack of long-term randomized controlled trials, <em><strong>a causal link between breakfast skipping and obesity has not been substantially identified.</strong></em></p></blockquote> <p>It’s certainly far from proven that breakfast skippers overcompensate due to hunger cravings and eat more <em><strong>as a result of</strong></em> skipping the first meal of the day. A 2013 study by <a href="http://www.ncbi.nlm.nih.gov/pubmed/23672851">Levitsky and Pacanowski</a> found that while skipping breakfast does lead to increased hunger by lunch time and eating of larger lunches, by the end of the day the breakfast skippers had spontaneously consumed 400 less calories per day than the non-breakfast skippers.  Overcompensatory eating did not occur.</p> <p>If skipping breakfast doesn’t lead directly to overeating and obesity, what explains the observed association? <em><strong>Perhaps eating late in the day “causes” breakfast skipping the next morning.  </strong></em>That may not be as strange as it sounds.  It could be that a large number of those who are obese skip breakfast because they overeat late into the night and wake up still feeling full from the previous night, delaying their eating until later in the day.</p> <p><strong>Myth 2:  It causes cardiovascular disease and metabolic dysregulation of blood glucose and hormone levels.  </strong>There is indeed some evidence that those who skip breakfast and also consume most of their calories after 6 pm put on more weight and are less healthy.  But is it the breakfast skipping or the late night eating that drives this?  Let’s take a look at a few studies that examined breakfast skipping and late night eating.</p> <p>A 2014 study of 1245 adults by <a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0108467#pone-0108467-t004">Bo et al</a>. found that consuming more of the daily energy intake at dinner is associated with an increased risk of obesity , metabolic syndrome and non-alcoholic fatty liver disease.</p> <p>A 2013 study by <a href="http://www.ncbi.nlm.nih.gov/pubmed/23512957">Jakubowicz et al.</a> found that when daily intake was fixed at 1400 calories, eating the larger 700 calorie meal for breakfast resulting in more weight loss and better metabolic markers than consuming the 700 calorie meal between 6 and 9 pm at night.</p> <p>A 2013 study by <a href="http://circ.ahajournals.org/content/128/4/337.full">Cahill et al.</a> at Harvard followed the eating patterns and cardiovascular health of over 26,000 men for 16 years. The men all started out free of Coronary Heart Disease.  But the men who skipped breakfast were found to have a 27% higher “risk” of CHD.  This alarming conclusion got a lot of press!</p> <p><a href="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Screen-Shot-2014-12-08-at-12.09.31-AM.png"><img class="aligncenter wp-image-5043" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Screen-Shot-2014-12-08-at-12.09.31-AM.png?resize=537%2C185" alt="Screen Shot 2014-12-08 at 12.09.31 AM" width="537" height="185" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Screen-Shot-2014-12-08-at-12.09.31-AM.png?w=673&ssl=1 673w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Screen-Shot-2014-12-08-at-12.09.31-AM.png?resize=150%2C51&ssl=1 150w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Screen-Shot-2014-12-08-at-12.09.31-AM.png?resize=300%2C103&ssl=1 300w" sizes="(max-width: 537px) 100vw, 537px" data-recalc-dims="1" /></a></p> <p>But such a bold headline deserves closer scrutiny.  Buried within the Cahill study are a number of surprises.  It turns out that the “risk” analysis was based on complex modeling that attempts to correct for numerous differences between the subgroups in order to tease out the “true” risks.  In fact, the <strong><em>actual incidence</em> </strong>of CHD “events” over the course of the 16 year study was….drumroll:</p> <ul> <li>5% among the breakfast skippers</li> <li>6% among the breakfast eaters.</li> </ul> <p><em><strong>So CHD events were actually 20% more frequent (6% vs.5%)  among the breakfast eaters than the breakfast skippers!  </strong></em></p> <p>Then why did Cahill et al calculate  a higher “risk” for the breakfast skippers? Answer: they “corrected” the results using a statistical model. They did in an attempt to account for the fact that in their particular sample of study participants,  breakfast skippers were different from the breakfast eaters in a number of key respects. For example:</p> <ul> <li>Breakfast skippers were 5 years younger on average than breakfast eaters</li> <li>15% of the breakfast skippers smoked vs. only 5% of the breakfast eaters</li> <li>Breakfast skippers consumed 37% more alcohol than breakfast eaters</li> <li>Cholesterol levels and other biomarkers differed between the two gropus</li> </ul> <p>Through the magic of statistics and multivariate modeling, <em><strong>Cahill et al. “adjusted” for a large number of other health and demographic factors, converting the absolutely lower CHD incidence of the breakfast skippers into a 27% higher risk!</strong> </em> Magic!  Yet the adjustment is paradoxical because — other than being younger — the breakfast skippers had a number of strikes against them, such as higher smoking and drinking rates.  So you would think the fact that their actual incidence of CHD was lower, would mean that the breakfast skipping behavior was protective, not risk-enhancing.</p> <p>The “corrections” made by Cahill’s team of modelers led to another head-scratcher:</p> <blockquote><p>In stratified analyses, among men ≤60 years of age, those who skipped breakfast had a 50% higher risk of CHD compared with men who ate breakfast (multivariate RR, 1.55; 95% CI, 1.09–2.22), <em><strong>whereas this association was not significant in the older half of participants</strong></em> (RR, 1.06; 95% CI, 0.84–1.33; <em>P</em> for interaction=0.01;</p></blockquote> <p>Huh?  If you believe the Cahill analysis, skipping breakfast increases your risk of CHD if you are younger than 60, but that risk suddenly disappears entirely after you reach age 60!  It seems to me that the Cahill analysis is an example of placing undue faith in a model, rather than taking the unvarnished incidence data at face value.  Data massaging for risk analysis is often warranted, but it can sometimes lead to perverse and nonsensical results, especially when the risk relationships are complex and non-linear, and when the absolute risks are relatively small and similar in magnitude.</p> <p><a href="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown-1.jpeg"><img class="alignleft wp-image-5024" src="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown-1.jpeg?resize=352%2C228" alt="Unknown-1" width="352" height="228" srcset="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown-1.jpeg?w=279&ssl=1 279w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown-1.jpeg?resize=150%2C97&ssl=1 150w" sizes="(max-width: 352px) 100vw, 352px" data-recalc-dims="1" /></a>If you still have confidence in the Cahill multivariate models, there is yet an even more alarming result:  Those who ate late at night or through the night had a 55% higher CHD risk than others, and this higher risk was mediated by body mass index, hypertension, hypercholesterolemia, and diabetes. Unlike the analysis for the breakfast skippers, a key point is that this difference persisted even independently of the statistical risk model.  In absolute terms,  over the 16-year study, fully 9% of the late night eaters had CHD, vs. 6% of the non-late night eaters — more significant than the impact of breakfast habits.</p> <p>In addition, Cahill found a 25-30% increase in CHD risk among those  who ate more than 5 times a day.  Snacker and grazers take note.</p> <p>A 2014 study by <a href="http://www.hindawi.com/journals/scientifica/2014/253581/">Kutsuma et al. </a>examined the eating habits of 14,068 Japanese adults with a variety of eating patterns. Multivariate analysis showed that <em><strong>the combination of late night dinner eating and breakfast skipping</strong></em> was associated with obesity and metabolic syndrome, and yet this association was absent in the case of either breakfast skipping alone or late night eating alone.</p> <p><em><strong>Looking at all these studies, we can ask:  What’s the real problem:  breakfast skipping, or eating frequently and late into the night?</strong></em></p> <p>We need to be careful not to link yabo亚洲 with effects that may originate from a very different pattern of eating — in which breakfast skipping is associated with a common cultural pattern of eating late at night and snacking frequently.  Many such breakfast skippers may start eating around lunchtime, and continues snacking and eating through the afternoon and evening, culminating in the midnight snack.  Maybe even “healthy” snacks. Know anyone like that?  By contrast, most who practice IF deliberately confine their eating to an interval of about 5-7 hours.  Typically, they skip breakfast, eating lunch and an early dinner, or perhaps just an early dinner, going to sleep on an empty stomach.</p> <p>Going to bed on a full stomach eliminates the nighttime fasting that kicks in for those who partake of lighter or earlier dinners.  Late eating may prevent the benefits of fasting and low insulin levels during sleep brought on by autophagy — the process of nutrient recycling that reverses the accumulation of metabolic damage and underlies many of the health benefits of yabo亚洲 .  If eating a big meal at night is followed by eating breakfast again early in the morning, there is not much of a “fast” to break, even if one waits until lunch for the next meal.  Autophagy kicks in only when you don’t eat for about 12 hours. (It can also be activated by severely restricting protein and/or carbohydrates).</p> <p><strong><a href="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown-3.jpeg"><img class="alignright wp-image-5034" src="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown-3.jpeg?resize=268%2C168" alt="Unknown-3" width="268" height="168" srcset="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown-3.jpeg?w=284&ssl=1 284w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown-3.jpeg?resize=150%2C94&ssl=1 150w" sizes="(max-width: 268px) 100vw, 268px" data-recalc-dims="1" /></a>Myth 3:  It’s bad for women, leading to hormone imbalance, disrupted menstrual cycle, and heightened stress response.</strong>   Recent articles by <a href="http://paleoforwomen.com/shattering-the-myth-of-fasting-for-women-a-review-of-female-specific-responses-to-fasting-in-the-literature/">Stefani Ruper</a> and <a href="http://forums.hardwarezone.com.sg/health-fitness-corner-48/poliquin-pros-cons-intermittent-fasting-4096693.html">the Poliquon blog</a> cite animal and human studies to substantiate this claim.  In her blog post, <a href="http://paleoforwomen.com/shattering-the-myth-of-fasting-for-women-a-review-of-female-specific-responses-to-fasting-in-the-literature/">“Shattering the myth of fasting for women”</a>, Ruper cites a combination of biological research, anecdote and personal experience to buttress her main thesis:</p> <blockquote><p><span style="color: #000000;">Many women find that with yabo亚洲 comes sleeplessness, anxiety, and irregular periods, among a myriad of other symptoms [and] hormone dysregulations.  I have also personally experienced metabolic distress as a result of fasting, which is evidenced by my interest in hypocretin neurons.  <a style="color: #000000; text-decoration: underline;" href="http://www.paleoforwomen.com/hypocretin-neurons-the-link-between-fasting-stress-and-arousal-or-why-fasting-breeds-insomniacs/">Hypocretin neurons</a> have the ability to incite energetic wakefulness, and to prevent a person from falling asleep, should his body detect a “starved” state.  Hypocretin neurons are one way in which yabo亚洲 may dysregulate a woman’s system…the mere fact of being more sensitive to the strains of fasting simply by being a woman is, I would assert, pretty important for a woman who is contemplating or already practicing IF.</span></p></blockquote> <p>Ruper’s reference to hyopcretin neurons draws upon a rat study by <a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0002398">Martin et al</a>., showing that 6 months of calorie restriction was beneficial for male rats but detrimental to female rats, causing them to “masculinize”.  The fasting female rats stopped ovulating, exhibited heightened alertness and memory, and slept less.  The authors showed that these changes came about by activating the hypocretin “arousal” system in the brain’s hippocampus.  These arousal and food-seeking behaviors are presumably beneficial as an evolutionary adaptation to starvation. Chronic activation of these arousal systems could interfere with reproductive capacity and cause other health problems.</p> <p>However, a closer look at the Martin et al. study makes it clear that <em><strong>none of the diets examined was a reasonable model of breakfast skipping or yabo亚洲 </strong></em>.  The five diets studied were:</p> <ol> <li>ad libitum (control diet)</li> <li>20% CR (calorie restriction)</li> <li>40% CR (calorie restriction)</li> <li>IF (yabo亚洲 )</li> <li>HFG (high fat / high glucose)</li> </ol> <p><a href="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Fatmouse.jpg"><img class="alignright wp-image-5014" src="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Fatmouse.jpg?resize=233%2C158" alt="Fatmouse" width="233" height="158" srcset="https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Fatmouse.jpg?resize=300%2C203&ssl=1 300w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Fatmouse.jpg?resize=150%2C101&ssl=1 150w, https://i2.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Fatmouse.jpg?w=640&ssl=1 640w" sizes="(max-width: 233px) 100vw, 233px" data-recalc-dims="1" /></a>Restricting calories by 20-40% is really quite severe, and it is not surprising that it could lead to loss of ovulation. But what about the so-called “IF” diet?  The article makes it quite clear that <em><strong>the IF diet was also a forced calorie restriction diet. </strong></em> Unfortunately, few details are provided regarding the precise degree of calorie restriction or the feeding schedule. However, the authors do give us this clue:</p> <blockquote><p>Whereas males on the HFG diet showed a greater increase in weight than those on the control diet, females on HFG and control diets gained similar amounts of weight. <em><strong>Males and females exhibited similar body weight responses to 20% CR and IF diets (i.e. a small increase in body weight).</strong></em> Both male and female rats responded to 40% CR by losing a significant amount of body weight during the study.</p></blockquote> <p>From this, together with the fact that the researchers explicitly state that the IF diet was calorie restricted, it is reasonable to infer that the IF diet was probably in the range of 20% calorie restriction.</p> <p><em><strong>Here’s the problem:</strong></em> Nothing about yabo亚洲 mandates or even recommends net calorie restriction! With IF, you eat all you want — you just eat it within a restricted time window. True IF is more like an “ad libitum” diet than a calorie-restricted diet, in that it allows your appetite to be fully sated.  The neat thing about IF is that it has been shown to provide many of the health benefits of calorie restriction <em><strong>without any actual net reduction in calories</strong></em>!  Quite a few IF practitioners do spontaneously reduce calorie intake over time, as their appetite adjusts.  But many IFers do not significantly cut back on calories — they just alter the temporal pattern of intake.  In either case, IF has been shown to provide health benefits.</p> <p>In short, the Martin et al. rat study cited by Ruper fails to say anything about yabo亚洲 the way most people practice it: without forced calorie restriction.  It’s certainly not the way I practice or advocate it.</p> <p>Ruper does seem to acknowledge the difference between calorie restriction and IF, but she appears to confute IF with longer term fasting:</p> <blockquote><p>It is well-known in both the research and the nutritional communities that caloric restriction is horrible for female reproductive health.  This is not news.  But what of fasting regimes?  Should women go long periods without eating, even if maintaining normal caloric input?</p></blockquote> <p>Long periods without eating?  Intermittent fasting involves short term breaks from eating of 12-24 hours, and the the degree of net calorie restriction can be modest to none.  We are not talking about “long periods” of going without food or any significant amount of calorie restriction.</p> <p>On that note, Ruper cites a 2005 study by <a href="http://www.ncbi.nlm.nih.gov/pubmed/15833943?dopt=Abstract">Heilbronn et al</a>. showing that alternate day fasting improved insulin sensitivity men, but slightly impaired glucose tolerance in women.  The study had a very small sample size (eight men and eight women) and the effects were slight, but even granting its validity, the protocol involved so-called Alternate Day Fasting (ADF).  This involves continuously alternating between 12-hour eating windows and 36-hour fasts for two weeks.   In my view, this is starting to push the fast a bit long. I certainly wouldn’t recommend ADF to anyone as an “introductory” version of IF.  Longer fasts require a period of adaptation.  I occasionally do longer fasts myself.  But my recommendation to newbies is always to start out gradually, by skipping snacks and then a few meals, rather than taking a heady plunge into longer fasts.</p> <p>One of the most common misunderstandings of hormesis that I encounter on this blog is a failure to appreciate the dramatic difference between modest, intermittent stress and intense, chronic stress.  <em><strong>yabo亚洲 is all about the benefits of low dose, intermittent stress</strong></em>.  This applies to exercise, diet, immune response, vision therapy and even psychology.  People think that if a little is good, a lot is better.  Moderation and gradualism are essential to reaping the benefits of hormesis.</p> <p><strong>Hormones out of whack?</strong> The posts by Ruper and the Poliquon Group also both cite a 2007 study of meal frequency by <strong>Stote et al</strong>, comparing consumption of three meals a day with consumption of the same amount of food once daily for dinner.  The results were a mixed bag:  Those eating a single daily meal lost body fat, and saw their cortisol levels decline.  However, they apparently also experienced greater hunger, less satiety, and modest elevations in blood pressure and LDL and HDL cholesterol levels.  Ruper’s verdict:</p> <blockquote><p><strong>In sum: </strong>patients on the one meal/day regiment were unhappy, hungry, lost a little bit of weight, increased cholesterol.  This was a small sample, included ~menopausal women, and all people of normal body weight.</p></blockquote> <p>A closer read, however, pinpoints some telling details. First, how was hunger measured?  “Subjective satiety and hunger were assessed daily <em><strong>before consumption of the evening meal</strong></em>“.  Well duh!  Obviously this is going to be <em><strong>precisely the  high point of hunger</strong></em> for those eating one meal per day, and hunger will obviously be much more attenuated for those who ate lunch just a few hours earlier!  Seems to me that it would have been fairer to do the hunger assessment <em>after</em> the dinner, or perhaps upon waking in the morning, for both treatments.   Personally, some increased hunger is a good thing, particularly if it makes food tastier and the meal leaves you satisfied.</p> <p>The <a href="http://forums.hardwarezone.com.sg/health-fitness-corner-48/poliquin-pros-cons-intermittent-fasting-4096693.html">Poliquon article</a> interprets the Stote article as evidence that yabo亚洲 causes hormone dysregulation:</p> <blockquote><p>The effect of yabo亚洲 on hormones and circadian rhythms is devastating. First, the entire hormonal cascade (metabolic hormones like insulin, anabolic hormones like testosterone and growth hormone, and energizing hormones of the adrenal glands) is interrelated. When one hormone-producing gland gets out of whack, you can bet that others will be negatively affected. This can produce any of the following: Poor metabolism and body composition, inability to build muscle, infertility, chronic fatigue, sleep disorders, a pro-inflammatory state, and increased risk of disease.</p> <p>A glimpse of this with yabo亚洲 comes from an 8-week study [Stote et al.] in which middle-aged people went on a 1-meal-a-day diet or a regular 3 meal-a-day diet—calories were not restricted. Results showed that the 1-meal-a-day group diet lost 2 kg of fat compared to the 3-meals-a-day group, however they also had a significant increase in blood pressure. Elevated blood pressure is indicative of altered circadian rhythms.</p> <p>In addition, cortisol, which was measured in the late afternoon before eating the 1 meal, was 48 percent lower than at baseline. This is further evidence of diurnal dysregulation. Yes, you want to minimize cortisol for health and body composition, but that doesn’t mean you want irregular cortisol, which is a symptom of adrenal fatigue.</p></blockquote> <p>Quite an indictment!  But this is taking a few tidbits out of context and wildly speculating about them.</p> <p>First of all,  the slight blood pressure elevation that Stote saw in the once-a day eaters was most likely an artifact of the time  of day at which blood pressure measurements were made, as Stote et al themselves suggest:</p> <blockquote><p>In animal models, yabo亚洲 without caloric restriction has been shown to decrease blood pressure and heart rate (<a id="xref-ref-15-1" class="xref-bibr" href="http://ajcn.nutrition.org/content/85/4/981.full#ref-15">15</a>). The observed increase in blood pressure in our subject population consuming 1 meal/d may be due to a circadian rhythm in blood pressure (<a id="xref-ref-23-1" class="xref-bibr" href="http://ajcn.nutrition.org/content/85/4/981.full#ref-23">23</a>). Diurnal changes may have occurred, because <em><strong>blood pressure measurements were obtained in the late afternoon in the 1 meal/d diet versus early morning in the 3 meals/d</strong></em>.</p></blockquote> <p>Second, the concern about the 48% drop in cortisol over the day is misplaced.  This is not dysregulation or a sign of “adrenal fatigue”.  To the contrary, it is perfectly healthy! According to <a href="//www.tennisbs.com/wp-content/uploads/2011/08/Chinook-Cortisol-and-DHEA-Diurnal-Patterns.pdf">Chinnock et al</a>. a normal cortisol pattern starts with a rise in the morning, followed by a gradual decline throughout the day, precisely as was found in the once-a-day eaters.  Later in this article, I’ll reference another study by Taylor et al., confirming normal levels of cortisol and other hormones in intermittent fasters, and no impact on the menstrual cycle.</p> <p>The Poliquon article’s charges of adverse hormonal effects of yabo亚洲 are unfounded.</p> <p>Another anomaly of the Stote study is that subjects eating once daily were required to eat the same amount of food as the three-meal-per-day group in a single setting.  <em><strong>All 2400 calories, whether they wanted to or not.</strong></em>  In other words, appetite was not allowed to control eating. Yet they still lost weight.  Imagine if it had been an ad libitum study.  Yet I think this is a big defect of the study and may be responsible for some of the negative effects on blood lipids and blood pressure. It is not a natural way to eat.  And it may have been responsible for the high dropout rate of the study.  As the authors note,</p> <blockquote><p>Our study withdrawal rate was 28.6%. Typical rates of withdrawal from human feeding studies at our facility are ≈4–7% (<a id="xref-ref-18-1" class="xref-bibr" href="http://ajcn.nutrition.org/content/85/4/981.full#ref-18">18</a>–<a id="xref-ref-20-1" class="xref-bibr" href="http://ajcn.nutrition.org/content/85/4/981.full#ref-20">20</a>). We can hypothesize that subject withdrawals increased because the subjects were asked to consume all food for the day in 1 meal; however, only 1 subject specifically stated this reason for withdrawing.</p></blockquote> <p>So far from stoking hunger, the authors worry that their once-a-day feeding protocol made subjects feel too full!</p> <p>Stote concludes with the view that IF might be OK for overweight women, but not for women of normal weight, light sleepers, those with irregular menstrual periods or conditions like acne.</p> <blockquote><p>The solution, then, in moving forward, is to look at options, to be honest about priorities, and to listen to one’s body with awareness and love.  Is fasting worth trying if a woman is overweight and trying to improve her metabolic markers, and so far hasn’t had much success?  Perhaps.  Should it be undertaken if a woman is of normal weight?   What if she is a light sleeper?  What if her periods begin to dysregulate?  Or stop?   What if she starts getting acne, getting a stronger appetite, or losing her appetite altogether?    These things happen, and I see them in women who fast and contact me time and time again.</p></blockquote> <p>These fears about yabo亚洲 seem unfounded.  Hormonal dysregulation might be associated with longer term fasting or other lifestyle or dietary conditions that raise cortisol.  But that is not the situation with IF, which was even shown to reduce cortisol levels.</p> <p>By failing to distinguish yabo亚洲 from extreme calorie restriction and long term fasting, I think that Ruper and others do a disservice to women in particular.  I know quite a few women who have adapted to IF quite well and swear that it has improved their health and their lives.  That fact that it works for some women quite well should be enough to refute the idea that IF is only suitable for men.  I do not  doubt that the transition to IF may be difficult for <em><strong>some</strong></em> women — but that is also true for <em><strong>some</strong> </em>men.  I’ll deal with the practicality of how do adapt to IF towards the end of this article.</p> <p><strong>True yabo亚洲 .</strong>  Now let’s look at a few studies that actually looked at <strong>real</strong> yabo亚洲 — eating less frequently (but generally at least once a day) and within a confined time window, but without any attempt to limit or equalize net daily calorie intake.</p> <p>A <a href="http://www.cell.com/cell-metabolism/pdfExtended/S1550-4131(14)00498-7">2014 Salk Institute study published in Cell</a> looked at true non-calorie-restricted yabo亚洲 in mice.  Unlike the Martin et al. study, these mice were allowed to eat all they wanted, but just within a restricted eating window.  Mice that ate within a 9-12 hour window ended up weighing significantly less than control mice allowed to eat as much as they wanted around the clock — even though they ended up consuming the same net amount of daily calories! The reduced weight gain was true even for rats given diets high in fat and sugar.  Even more impressively, the IF rats maintained good lipid profiles and insulin sensitivity, unlike control rats that could feed ad libitum.  Interestingly, the strong weight control and metabolic benefits persisted even when the rats were allowed to go off the diet on weekends!  A slightly longer 15-hour eating window provided more modest benefits.</p> <p>Great for rats, but how about humans, and specifically women?</p> <p><a href="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown-4.jpeg"><img class="alignleft wp-image-5035" src="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown-4.jpeg?resize=415%2C276" alt="Unknown-4" width="415" height="276" srcset="https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown-4.jpeg?w=275&ssl=1 275w, https://i1.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/Unknown-4.jpeg?resize=150%2C99&ssl=1 150w" sizes="(max-width: 415px) 100vw, 415px" data-recalc-dims="1" /></a><a href="http://press.endocrine.org/doi/full/10.1210/jcem.84.2.5502">A 1998 study of meal frequency in women by Taylor et al.</a> compared the metabolic effects of eating 3 daily meals plus a snack versus a single daily dinnertime meal of equal daily caloric, macronutrient and micronutrient composition. The same seven women were studied eating these two different patterns for two separate 3-day study periods.  It should be pointed out that the investigators approached this study with the mindset that “the ingestion of fewer large meals may be metabolically worse than the ingestion of frequent small meals.”  The fact that the authors <b><i>labelled</i></b> the eating of one daily meal as “binge eating” rather than “yabo亚洲 ” tells you something about the investigators’ presumptions!   With that said, it’s worth looking at what this study actually found:</p> <blockquote><p>Ingestion of an entire day’s calories at dinner resulted in a significant increase in fasting glucose levels and a dramatic increase in insulin responses to the evening meal. The diurnal pattern of leptin secretion was altered, such that the gradual rise in leptin from 0800 h observed during the normal diet was abolished, and leptin did not begin to rise during the binge diet until at least 2 h after the evening meal.</p></blockquote> <p>This is of course not at all surprising.  The question is whether it a more concentrated peak rise in glucose and insulin, and change in the timing of the leptin peak could result in hypothesized insulin resistance or hormonal dysregulation, based on prior studies associating these problems with “binge eating”.   It turns out that those fears were not actualized:</p> <blockquote><p>No changes were demonstrated in insulin sensitivity, follicular growth, or ovulation between the two diets….Importantly, there was no difference in cortisol excretion between the two diets.</p></blockquote> <p>It is also worth pointing out that despite higher morning (“fasting”) blood glucose levels on the once-daily pattern (94 mg/dL) vs. multi-meal (86 mg/dL), <em><strong>the average blood glucose over the day  for the once-daily  pattern (97 mg/dL) was significantly lower than for the multi-meal pattern (107 mg/dL)</strong></em>.  It seems to me that average blood glucose is a better indicator than a single morning reading of what your brain and peripheral tissues are seeing most of the time.  And 97 is definitely better than 107!   Eating once a day may cause bigger “spikes” in blood sugar but average blood glucose levels are lower, and remain lower for a more sustained, uninterrupted time. Adaptation to this pattern can be especially valuable for people with blood sugar issues, because elevated blood sugars can cause all sorts of problems.</p> <p>Somewhat surprised that their study found no problems with one meal per day, Taylor at al. ended their paper with the suggestion that perhaps something more is involved with true binge eating than merely reduced meal frequency:</p> <blockquote><p>as most binge eating episodes in the population are associated with the ingestion of excess calories, <em><strong>it is hypothesized that</strong> <strong>binge eating behavior is associated with even greater metabolic dysfunction than that described herein.</strong></em></p></blockquote> <p>Indeed.  Binge eating, like bulimia and anorexia, is a true eating disorder.  Eating disorders typically arise from issues associated with body image and self-control, perhaps exacerbated by a poor diet or metabolic dysfunction.  But binge eating should not be confused with yabo亚洲 .  Practitioners of IF are motivated by its documented health benefits and additionally by the freedom to offers from cravings and food obsessions.</p> <p><strong>Conclusions and recommendations.</strong>  The purpose of this post was not to make the positive case for yabo亚洲 . For that, you can check out the hyperlinks in the first sentence of this post, or watch my talk on <strong><span style="color: #993300;"><a style="color: #993300;" href="//www.tennisbs.com/2011/05/intermittent-fasting-for-health-and-longevity/">Intermittent Fasting for Health and Longevity</a></span></strong>.  Rather, this post attempts to examine and respond to some recent claims that IF can cause obesity, cardiovascular disease, and disordered glucose, hormone levels, and menstrual cycles.  I believe that these criticisms hinge upon several fundamental misunderstandings of IF and misinterpretations of a number of scientific studies.  By closely examining the evidence, we can draw two main conclusions.</p> <ul> <li>Many breakfast skippers are indeed overweight or unhealthy, but this most likely reflects other associated habits such as frequent snacking and eating late at night.  IF is best practiced by confining eating to a 4-6 hour window, and preferably eating dinner early and well before bedtime.</li> <li>While dysregulation of hormones and menstrual cycles can be disrupted by severe calorie restriction and very long fasts, there is no evidence that such problems result from shorter daily fasts of about 12-24 hours.</li> </ul> <p>While I believe that yabo亚洲 is generally safe for most people, including women, I think there are better and worse ways to implement it.  Many have stated that IF is not suitable for people with diabetes, hypoglycemia or other metabolic issues. However, I’ve heard and read of many instances of people who used IF to reverse those conditions — to normalize blood glucose and lipids and to bring hunger and hypoglycemia under control.  For just one instance of this, read this inspiring post by Lee Shurie, who reversed his diabetes using IF:</p> <p><strong>How I defeated Type II Diabetes</strong></p> <p>Of course, I have no doubt many of you reading this have had very negative personal experiences trying yabo亚洲 . But I suspect that many of the negative experiences that some individuals have had with IF stem from making a very common and understandable mistake:  <em><strong>moving too quickly.</strong></em></p> <p>If you are habituated to a pattern of eating three or more meals a day plus snacks, trying to suddenly switch to one meal a day may be a bad idea.  While some people can do that (I did), many will find it to be both psychologically and physically intolerable. Eating and appetite are under the control of a complex system of hormones and enzymes.  It can take weeks to change the timing of induction and secretion of these modulators.  Symptoms can range from hunger pangs and unbearable cravings to headaches, hypoglycemic light-headedness, sweating and fainting. Not a good idea.</p> <p><em><strong>I strongly advise gradualism.</strong></em>  Make small changes each week and allow them to set in before proceeding further.  First, eliminate between-meal snacks and avoid eating for at least an hour before bedtime.  Those changes can be hard enough and may take weeks to adjust to. But even that first step is already beneficial. Once snacking is eliminated, try delaying breakfast rather than skipping it.  Eventually you may be able to skip breakfast.  You can also try to finish eating dinner earlier and avoid eating after 8 p.m.</p> <p>Interestingly, the benefits of yabo亚洲 can be significant even if you can manage a 12-18 hour mini-fast once or twice a week.  You don’t have to do it every day to see health improvements.  Of course, if you can skip breakfast 5 or more days a week, more power to you.</p> <p><a href="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/images-11.jpeg"><img class="alignright wp-image-5037" src="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/images-11.jpeg?resize=286%2C214" alt="images-1" width="286" height="214" srcset="https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/images-11.jpeg?w=259&ssl=1 259w, https://i0.wp.com/www.tennisbs.com/wp-content/uploads/2014/12/images-11.jpeg?resize=150%2C112&ssl=1 150w" sizes="(max-width: 286px) 100vw, 286px" data-recalc-dims="1" /></a>Your appetite will adjust, as your hormone and enzyme levels gradually change to the altered eating schedule.  Just as Pavlov trained his dogs by repetition, <a href="http://press.endocrine.org/doi/full/10.1210/en.2005-1345">you can train your mind and digestive apparatus</a> to learn a new pattern. Hunger is much more susceptible to conditioning that you may think — read this <a href="http://www.newyorker.com/science/maria-konnikova/why-do-we-eat-and-why-do-we-gain-weight">New Yorker article</a> and my page on Appetite the <strong><span style="color: #993300;"><a style="color: #993300;" href="//www.tennisbs.com/diet/">Deconditioning 亚搏体育客户端下载 </a></span></strong>.  And be patient!</p> <p>I’ve summarized my recommendations on transitioning to yabo亚洲 in an earlier post, <strong><span style="color: #993300;"><a style="color: #993300;" href="//www.tennisbs.com/2010/11/learning-to-fast/">Learning to Fast</a>.</span></strong>  It includes a lot of useful tricks, such as the use of “training snacks”.  Learned correctly, yabo亚洲 doesn’t ramp up hunger — it tames hunger. Many people have told me that post was very helpful in helping them adjust to yabo亚洲 with a minimum of effort and discomfort. I’d be interested in additional feedback and comments from others regarding what has or has not worked for you in your efforts at yabo亚洲 .</p> <p>Happy (and gradual) yabo亚洲 …just in time for the Holidays!</p> //www.tennisbs.com/2014/12/is-it-dangerous-to-skip-breakfast/feed/ 20 4764