Mitochondria are the ‘energy powerhouse of the cell’ that convert the foods we eat to usable energy our body uses to fuel life sustaining reactions within cells, our daily activities and athletic performance 1-4. While energy production capability and muscle performance might seem to be more relevant to sports, it also equally important for achievement and maintenance of health throughout the life span. In this article I will describe how chronological aging affects our mitochondria, its implications and the ins-and-outs of a new type of supplements marketed at “exercise mimetics”.

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Exercise Mimetics

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Age related mitochondrial changes and implications
Brain, heart, and skeletal muscle mitochondria are especially susceptible to age-induced declines in the capacity to produce energy (ATP), and ability to respond to increased energy demands 2-6. It is well documented that mitochondrial number, mass and function declines with aging 2-5, and that this decline plays an important role in the etiology of many disorders, including cardiovascular diseases, obesity, diabetes, neurodegenerative diseases, and cancer 7-15. Physical inactivity and poor exercise capacity is a risk factor not only for the development of these diseases 8 16-18, but also causes frailty, age-related physiologic functional declines 19-22, and accelerates secondary aging (i.e., aging caused by diseases and environmental factors) 15.
The importance of exercise for mitochondrial function and prevention of age-related declines
We all know that exercise training increases muscle mitochondria number, mass and function 23-26. Regular exercise counteracts the age-related decline in muscle mitochondrial expression and function 27-32 and protects against development of age-related metabolic diseases like the metabolic syndrome, obesity, and diabetes 9 28 29 33-36. Thus, regular exercise increases healthy life expectancy and prolongs life span through beneficial effects, in large part, at the level of the mitochondria 28.
Muscle is the tissue with the largest capacity to increase caloric expenditure and energy production, and possesses the unique ability to increase metabolic rate nearly 100-fold during the transition from a basal resting state to maximal contractile activity 37. Being such a metabolic prowess, the importance of mitochondria in muscle tissue is obvious. However, exercise training also has beneficial effects on mitochondria in other tissues, especially the heart 38 39, and brain 40. In the resting state, these tissues actually consume more calories on a per gram basis than does muscle tissue 41 42. Several of the beneficial cardioprotective effects of exercise training can be traced to improved cardiac mitochondrial function 38, and regular exercise also increases brain mitochondrial biogenesis 40. This may have important implications, not only with regard to fatigue, but also with respect to various central nervous system diseases and age-related dementia that are often characterized by mitochondrial dysfunction 40.
Recent advances in molecular biology have shed light on the mechanisms that regulate mitochondrial biogenesis (production of new mitochondria), and how exercise stimulates mitochondrial biogenesis. This is interesting not only from a physiological standpoint, but also from practical standpoint since it has allowed discovery of dietary substances (and potentially drugs) that could help us combat the age related mitochondrial decline. More on this in a bit. First, let’s take a quick look at what happens to our mitochondria when we exercise.
Mitochondria at the molecular level – exercise induced signaling targets
Energy stress from exercise triggers a host of signaling pathways in muscle cells 43-47. One of the identified exercise-induced signals is AMPK (AMP-activated protein kinase) 48-50. AMPK functions as a metabolic “fuel sensor” in muscle cells because it becomes activated in response to decreased energy levels (like for ex. during muscle contractions), and in turn activates catabolic processes that generate and restore ATP levels 48 51 52.
Another energy sensor is SIRT1 (Sirtuin-1) 51 53 54. There are actually seven sirtuins 55;  they have generated a lot of scientific interest after the discovery that sitruins partly mediate the increase in longevity with calorie restriction that has been seen in lower organism and animals 56-60. But sirtuins regulate a wide range of important biological processes 61. One of them is muscle precursor cell (MPC) proliferation. The finding that SIRT1 increases muscle precursor cell proliferation is very interesting since MPC proliferation has important implications in regulating muscle growth, maintenance, repair, and the aging-related loss of skeletal muscle mass 62.
Adult muscle stem cells, also called satellite cells or muscle precursor cells (MPCs), play an important role in the remarkable ability of muscle fibers to grow in size, repair and regenerate 63 64. A hallmark of aging is diminished regenerative ability of muscle tissues, which is in large part due to age-related changes in tissue-specific stem cells 65. Muscle precursor cells are important not only for regeneration after tissue damage, but also for maintenance. Age-related muscle loss (sarcopenia) is caused in large part by atrophy of type II muscle fibers 66, which is associated with a fiber type-specific decline in muscle precursor cell content 66. Thus, SIRT1 is an attractive target for dietary/exercise interventions to prevent the loss of muscle mass and function with aging 66.
SIRT1 also works jointly with AMPK in regulating cellular fuel metabolism, inflammation, and mitochondrial function 51. In addition, SIRT1 activates and increases the activity of PGC-1 (peroxisome proliferator-activated receptor-γ coactivator,  a transcriptional coactivator), which finally activates transcription factors that turn on genes in our DNA that produce new mitochondria 23-25 54 67. One such transcription factor is PPAR-gamma, which also contributes to mitochondrial biogenesis 68.
Of the mentioned “control points” (AMPK, SIRT1, PPAR-gamma and PGC-1), PGC-1 is considered the “master regulator” of mitochondrial biogenesis 69-71. It also increases oxidative phosphorylation and ATP (energy) production 71. As a result, increased expression of PGC-1 has been shown to increase peak oxygen uptake and delay fatigue during prolonged exercise 69. In addition to its stimulatory effect on mitochondrial biogenesis and function, PGC-1 also regulates muscle fueling stores by increasing muscle glucose uptake, augmenting muscle glycogen storage, and preventing muscle glycogen depletion during exercise 72.
Ok, now you know enough molecular biology to understand the rationale behind exercise mimetics, which we will focus on next.
Exercise Mimetics
Elucidation of the molecular mechanisms behind mitochondrial biogenesis and function, coupled with the identification of dietary substances that seem to increase the expression of PGC-1, SIRT1, AMPK etc. and/or their regulators, has led to great interest in developing drugs and dietary supplements to target the SIRT1-PGC-1 complex and related signaling pathways 47 50 73-75.
Because these supplements and drugs activate some of the signaling pathways that are activated by exercise, they have been labeled as “exercise mimetics” 47 74. Here’s a rundown of some dietary bioactive substances that are currently in the scientific spotlight for their potential exercise mimetic effects.
PQQ (short for Pyrroloquinoline Quinone, and also called methoxatin) is a less well known dietary compound that was discovered 1979 76-78. PQQ is present in tissues and body fluids, including human milk 79-81 and in foods. The richest dietary sources are 82:
Natto (fermented soybeans)         61 ng PQQ/g
Parsley                                               34 ng PQQ/g
Green tea                                          30 ng PQQ/g
Green pepper                                   28 ng PQQ/g
Kiwi                                                     27 ng PQQ/g
Papaya                                               27 ng PQQ/g
Tofu (soybean curd)                        24 ng PQQ/g
Spinach                                              22 ng PQQ/g
Carrot                                                17 ng PQQ/g
When you read supplement labels, remember that 1 milligram (mg) = 1,000,000 nanogram (ng)
PQQ acts as an antioxidant 83, enzyme cofactor 84-91, nero-protectant 92-95, cardio-protectant 96-98, and may have an important role in cell signaling 92 99-101. In this context, the most interesting function of PQQ is that it affects the expression of genes involved in mithochondrial functions and biogenesis (most notably, PGC-1) 99 102.
The nutritional importance of PQQ has been demonstrated by feeding rats and mice a diet that is devoid of PQQ; the animals show growth retardation, reproductive failure, compromised immune responses, skeletal deformities aortic aneurysms, and fragile skin 91 103 104. This strongly suggests that PQQ is necessary for normal body functions and health. It is actually being debated whether PQQ might become the “next vitamin” 78 88.
What’s more interesting is that varying the amount of PQQ in diets causes modulation in mitochondrial content, alters lipid metabolism, and reverses inhibition elicited by classical mitochondrial function inhibitors 97 104-106. PQQ deficiency decreases both mitochondrial function and number 106. The most recent study on PQQ fed rats a nutritionally complete diet either with or without PQQ 105. The rats that got the PQQ diet not only exhibited lower blood triglycerides but also showed increased energy expenditure, hepatic (liver) mitochondrial content. In contrast, the rats that were fed the PQQ deficient diet instead exhibited deterioration in mitochondrial function, a lowered energy expenditure and reduced capacity to oxidize fat for energy (that is, reduced fat burning) 105. However, at the time of this writing, no human study has investigated the effect(s) of PQQ on metabolic, muscular and mitochondrial parameters. PQQ can already be found on the supplement market, but for now we will have to be our own lab rats.
A natural polyphenolic flavonoid, quercetin is present in a wide variety of food plants, including red onions, apples, and berries 107 108. Known for its multiple health benefits 109-118, it has recently been shown that quercetin also beneficially affects mitochondrial energetics 119 120 and stimulates mitochondrial biogenesis (by increasing expression of PGC-1alpha and SIRT1) 121. The quercetin-induced increase in mitochondrial biogenesis was accompanied 121 with both maximal endurance capacity and voluntary wheel-running activity in mice 121.
However, findings from the few research studies on the ergogenic (i.e. performance enhancing) effects of quercetin supplementation in humans are equivocal 122-127. A small preliminary study showed that when given in combination with other antioxidants for 6 weeks, quercetin improved endurance time-trial performance on a bicycle ergometer in humans 126. Another study, conducted by the same research team that showed performance enhancing effects in mice, gave healthy but untrained participants 500 mg of quercetin twice daily. After 7 days it was shown that the quercetin supplementation resulted in a modest increase in VO2max along with a substantial (13.2%) increase in ride time to fatigue 125. It was concluded that quercetin supplementation can increase endurance without previous exercise training in untrained participants 125. In contrast, another controlled study conducted by another research team, which gave young healthy recreationally active men 1 g/day of quercetin in a sports hydration for 16 days failed to show any benefits over placebo; the quercetin supplementation did not improve neither muscle oxidative capacity or performance in a 10 min maximal-effort cycling test 124. Also, supplementing with 1 g/day of quercetin for 3 weeks in trained cyclists failed to show a performance benefits 127.
A recently published meta-analysis of human studies on quercetin and performance concluded that quercetin supplementation significantly endurance performance, but that the effect is very small 128. The computed effect size for the performance enhancement was 3-5% over placebo 128. This can be compared to the effect size for the performance enhancement with caffeine, which is in the range of 12% over placebo 129. If at all, people with low fitness levels will probably most likely experience a performance benefit of quercetin supplementation, since highly fit individuals already have an elevated mitochondrial density and function.
There is a possibility that a longer supplementation duration is necessary for quercetin to exert a performance enhancing effect, and/or that it could be ergogenic in elderly. Hopefully, future studies will address that. Thus, while quercetin is a prudent supplement to take for its beneficial health effect, if you’re looking for a boost in mitochondrial function and/or performance, don’t expect too much.
Resveratrol is the most well known SIRT1 activator 130-132. A  natural compound present in grapes (especially grape skin) 133 134, resveratrol has been in the spotlight since it was found to be one major factor explaining the French paradox and conferring the cardioprotective effect of red wine 135-140. Fresh grape skin contains about 0.05-0.1 mg resveratrol per gram, while red wine is a concentrated source of resveratrol providing up to 14 mg per liter. Resveratrol also protects against cancer 135, and induces several signaling pathways that are also seen with calorie restriction (I will cover this more in an upcoming article on calorie restriction mimetics).
More recently, it has been shown that resveratrol also might improve mitochondrial function and stimulate mothochondrial biogenesis 131 141. In mice, intake of resveratrol together with habitual exercise, suppresses the aging-related decline in physical performance 141. This effect was attributable, at least in part, to improved muscle mitochondrial function 141. Another mice study showed that resveratrol increases aerobic capacity, as evidenced by an increased running time to exhaustion 131. On a molecular level, this effect was paralleled by an induction of genes for oxidative phosphorylation, increase in PGC-1alpha activity and enhanced mitochondrial biogenesis 131. Resveratrol also seems to be able to counteract muscle atrophy during periods of physical inactivity (mechanical unloading) in rats 142.
However, while there is ample of human data on the health promoting effects of resveratrol, at the time of this writing there are no human studies on its potential mitochondrial, metabolic and/or performance enhancing effects.
Another potential mitochondrial booster is naringin, which like nootkatone, is a flavonoid present in grapefruit, and also in other citrus fruits 170 171. Upon ingestion, the colonic microflora converts naringin to naringenin, which is the active form in the body 172.  In contrast the other bioactive compounds mentioned in this article, naringin primarily targets the liver, where it activates both PPAR-gamma and PPAR-alpha with a concomitant increase in hepatic fat oxidation (fat burning) and inhibition of fat and cholesterol synthesis 173. An interesting recent finding is that naringin also seems to induce PGC-1 transcription, and thereby possibly could stimulate mitochondrial biogenesis in the liver as well. Since the liver is the metabolic hub in the body, this could have beneficial systemic (whole-body) effects. Naringin has already been shown in humans to have several beneficial health effects by preventing cardiovascular disease, protecting against cancer and being anti-inflammatory 171 174-177, so if you try this supplement it won’t hurt you even though the evidence for its potential effect on mitochondrial biogenesis is still in its infancy.
The potential of exercise mimetics certainly appeals to the huge mass of lazy folks who cannot get their butts off the couch, and the pharmaceutical and supplement industry that sees the tremendous market potential. So we’ll most certainly be hearing a lot about these “exercise pills” in the near future. However, I want to emphasize that an “exercise pill” will never ever be a substitute for actual exercise training. Why? For several reasons:
Firstly, mimicking activation of exercise signaling pathways could result in a chronic catabolic state. For example, activation of AMPK could inhibit protein synthesis 152 and stimulate autophagy (cell cannibalism, that is, degradation of a cell’s own components through the lysosomal machinery) 153. Also, while augmenting oxidative capacity in mice, overproduction of PGC-1α in muscle has been shown to result in severe muscle atrophy as mice aged 154. These effects would clearly be detrimental, especially for aging people. This underscores the importance of striking an optimum balance between continuous compared with transient activation of exercise signaling pathways.
Secondly, intense exercise bouts induce significant temporary stress on various organ systems. With an over 15-fold increase in whole body oxygen consumption when transitioning from complete rest to intense exercise, it is no surprise that a complex myriad of signaling pathways are activated in multiple tissues, of which we only know a few. Even though science is making progress in elucidating the exercise response on a molecular level, we are still barely just scraping the tip of the iceberg.
Thirdly, exercise training has multiple health benefits that do not, at least directly or entirely, relate to the muscle-specific adaptations. For example, cardiovascular adaptations like blood pressure reduction and improved blood lipid profile are not completely (albeit partly) due to muscle-specific adaptations 155 156. This is further underscored by the finding that beneficial effects of regular exercise are even seen in arteries of non-exercise-trained limbs 157-160. Additionally, regular exercise results in a host of other health benefits; it prevents or reduces the severity of dementia and other neurological disorders, osteoarthritis, osteoporosis, fall-related injuries, depression, certain cancers and cardiovascular diseases 16 18 161-165. Exercise also improves cardiac function and enhances stroke volume, increases VO2max (the maximal oxygen uptake, or aerobic capacity, which is the maximum capacity of the body to transport and use oxygen during exercise), increases nitric oxide levels in vascular endothelial cells, increases bone mass and strength, enhances the immune system, lowers TNF-α and other inflammatory markers, improves insulin sensitivity and blood lipid profiles, and increases muscle capillarization, muscle size and muscle strength 161 166. Obviously, no single pharmaceutical or dietary agent could mimic this multifaceted response.
Fourthly, in order for an “exercise mimetic” to mimic the effect of exercise on obesity, it would have to result in an increase in energy expenditure to the same degree as exercise. Even though PQQ increases energy expenditure in rats (see above), this increase is nowhere near the increase that is seen with exercise. An increase in muscle mitochondria enhances exercise capacity and endurance, making it possible to expend more total energy, or the same amount of energy in a shorter time. So, an increase in mitochondria enhances the capacity to expend calories by means of exercise, and thereby could make exercise more effective in preventing and/or treating obesity. However, an increase in mitochondria per se has no major independent effect (in the absence of exercise) on energy expenditure.
Finally, regular exercise has psychological effects on constructs like self-mastery 167, self-esteem 167, self-perception 167, self-efficacy 168 self-regulation 168 and also social engagement 167, which no “magic” mimetic pill ever will be able to reproduce. The psychological effects of exercise might actually be at least as important as the physiological effects in the achievement of fat loss 154.  This is an areas that I think deserves more attention.
A poly-pill containing a number of agents aimed at selected targets could theoretically address the second and third objection. However, as indicated in objection one, it is likely to be associated with multiple unwanted effects, and to be of questionable long-term efficacy. Thus, with the discovery and development of tissue-specific targets, only limited aspects of the exercise response can be mimicked. The term ‘exercise mimetic’ is therefore misleading, and could lull a false sense of security and give lazy folk another excuse not to exercise “I took this exercise pill so I don’t have to go to the gym”…. These days, unfortunately the general tendency is to look for a pill to solve our problems anytime we face obstacles. This fact is aptly highlighted by a comment from one of the most prominent researchers on the health benefits of regular physical activity “When will we treat physical activity as a legitimate medical therapy…even though it does not come in a pill?” 169.
Exercise mimetics work by stimulating some of the molecular pathways that are also activated by actual exercise. Pharmacological stimulation of AMPK and PGC-1 in sedentary mice has been shown to induce metabolic genes and enhanced running endurance even without exercise 50. Similarly, SIRT1 activation could protect against metabolic disorders by stimulating fat burning (oxidation). Also, the question remains as to what extent data from cell culture and rodent studies can be extrapolated to humans.
However, the terms “exercise mimetic”, and its synonym “exercise pill”, are very misleading. I prefer the term “mitochondrial booster”, since it doesn’t erroneously imply that these types of pills can substitute for the real thing. A mitochondrial booster (or exercise mimetic, if you wish) supplement could be a great adjunct to exercise, but never ever a substitute.
Bearing all the caveats in mind, since actual exercise and exercise mimetics at least partly target the same molecular pathways at potentially complementary control points, it is extremely interesting to speculate on the possible synergistic effects between exercise and exercise mimetics on muscle, mitochondrial function, performance, and in preventing the age-related declines in muscular function…indeed, there are preliminary data pointing towards promising synergistic effects 50. Rest assured I will be keeping you posted here on
However, exercise is and always will be necessary. Sorry folks, there are no magic bullets. There’s simply no way around it. Amen!!!
So here’s the take-home message:
If you are a regular exerciser; an exercise mimetic/mitochondrial booster could give you a little extra “push” and possibly enhance your long-term training response.
If you are a couch potato; no pill in the word will ever make up for your lazy ass!
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About Monica Mollica >
Monica Mollica has a Bachelor’s and Master’s degree in Nutrition from the University of Stockholm, Sweden, and is an ISSA Certified Personal Trainer. She works a dietary consultant, health journalist and writer for, and is also a web designer and videographer.
Monica has admired and been fascinated by muscular and sculptured strong athletic bodies since childhood, and discovered bodybuilding as an early teenager. Realizing the importance of nutrition for maximal results in the gym, she went for a major in Nutrition at the University.
During her years at the University she was a regular contributor to the Swedish bodybuilding magazine BODY, and she has published the book (in Swedish) “Functional Foods for Health and Energy Balance”, and authored several book chapters in Swedish publications.
It was her insatiable thirst for knowledge and scientific research in the area of bodybuilding and health that brought her to the US. She has completed one semester at the PhD-program “Exercise, Nutrition and Preventive Health” at Baylor University Texas, at the department of Health Human Performance and Recreation, and worked as an ISSA certified personal trainer. Today, Monica is sharing her solid experience by doing dietary consultations and writing about topics related to bodybuilding, fitness, health and anti-aging.
  1. RICH 7 years ago


    • Will Brink 7 years ago

      Rich, I suggest you read the article again, and closer in terms of the actual details. The “downsides” of such an approach are also covered, etc.and it’s made clear such an approach will not replace exercise…. Regardless, the science is the science, one does not have to “like it” for it to exist.
      Two, typing in all caps = yelling at people on the ‘net, which I’m sure is not your intent. 🙂

      • Jordan Zakery 7 years ago

        Also Rich, for all of the lifters out there (including myself), this stuff is important for maximizing your progress. With out understanding nutritional science, your workout may be wasted. What I appreciate about the BrinkZone is that it takes away the “we just lift” mentality and looks at fitness in a structural perspective. Since learning of this website and heading its advice I have had a lot of progress in the gym. Such as understanding the science behind why brocolli and spinach in the diet is imperative for body cleansing and resisting injury. Science is everything in fitness because your body is a product of science!

  2. Kevin Stevens 7 years ago

    Fascinating article from Monica. Understandable to the layperson yet supported by solid science. Everyone who exercises regularly, intuitively knows the conclusions this article presents; to lose weight, build or maintain muscle and health, one must eat correctly and get up off the couch to exericse.

    • Monica 7 years ago

      Yes. The article is aimed at both regular exercisers and non-exercises alike, with a different take-home message:
      If you are a regular exerciser; an exercise mimetic/mitochondrial booster could give you a little extra “push”.
      If you are a couch potato; no pill in the word will make up for your lazy ass!

      • Dukeye 7 years ago

        LOL Yes, and people would certainly work out with intensity at their mandated fitness classes! 😛 I’m not saying remove the profit motive and liberty to choose, but perhaps having physicians (not under HMO management) properly trained to treat folks with nutrition, exercise prescription, and lifestyle management instead of (poly)pharmaceuticals as a first resort.

  3. John 7 years ago

    Not to say there aren’t people that understand this level of detail but I have to agree with Rich that the granularity of the article is far more detailed than most people comprehend or can benefit from. Still a very informative read and although there’s no substitute for exercise, I’d like to get my hands on these pills and see how they’d benefit an an aging 47 year old wannabe bodybuilder like me…

    • Will Brink 7 years ago

      John, as you know, the BrinkZone info ranges from “hard” science (highly detailed, granular, lengthy, etc) to very simple (Shake Weight Review!) to silly fun, and everything between. I think people without science backgrounds can still get the ‘take home’ message from this article if they apply themselves and take some time to see what her big picture conclusions are.

  4. Lynn Johnson 7 years ago

    Great article. Too much reliance on pills leads to disappointment. I am taking Resveratrol because I test my blood glucose in the morning, and found I dropped 10 points, from 92 down to low 80s with 100 mg twice a day. I argue that we should never take something if we can’t measure the body’s response.

  5. Kathleen 7 years ago

    Thanks, Monica! At 56, I am all for doing whatever I can to boost mitochondrial functioning and biogenesis. Your article has me about to order some PQQ caps from Life Extension. And you are so right. The psychological effects like self-esteem, acquired through exercise, are huge. When you feel your body start to slow down, your recuperative abilities decline and your ability to gain muscle/lose fat stall, it’s a challenge to push on. Whatever can help is a blessing.

    • Monica 7 years ago

      You’re welcome Kathleen 🙂
      I’m glad you get the message; supplements can help but never substitute for the real thing, which is exercise combined with a proper diet.
      Keep it up!

  6. Dukeye 7 years ago

    I enjoyed reading a blog article with 169 citations – this is a piece I can trust. Most articles on such topics just give you someone’s opinion, maybe food for thought or something to research later. After reading this, I don’t need a whit more info on ‘exercise mimetics’.
    As to when physical activity will be considered legitimate medical treatment…maybe when incentives are provided for the medical system to keep people healthy, instead of funneling the maximum amount of money to pharmaceutical companies, insurance companies, management companies, etc.

    • Monica 7 years ago

      I’m glad you find my article informative and solid. It gives me goosebumps when I ready lay or popular press publications that only tell one side of the story, or make biased conclusions without any references. That’s why my articles tend to be a bit long; a bit simplification might be necessary in order for non-scientific folks to understand, but too much simplification runs the risk of causing confusion and downright erroneous messages.
      Yes, the government should make it a mandate to have people take 1-2 hours off from work every day just to exercise, and compensate the employers and pay for gym memberships. That way there would be no “I don’t have time” or “I cannot afford” BS excuses! And it would generate more jobs since more gyms would have to open up 🙂 🙂

  7. Jeff 7 years ago

    Thank you Monica. I love research oriented articles like this. The data is right there in the citations, which means we are reading about facts, not vague opinions. And I completely disagree with Rich, the article means a lot to me. I use supplements as a complement, not a substitution for exercise. If there is a supplement that I feel has enough evidence to suggest a health benefit I’m looking for, I might try it. I

  8. Scott I 7 years ago

    Will, I loved this article. I am up on it, anyway, but I would think the body/muscle builders wold be delighted in hearing about supplement stimulators that do not present any known dangers and do add significantly to enhancing muscle growth. Loved the references since many would tend to doubt the authenticity without them. the Brink Zone is, in my mind, 100% science backed and that is why I come here exclusively for info on a regular basis. I like Life Extnesion Foundation but they have aversions to focus on bodybuilding though their findings often touch on it lightly.
    I note that some do not like the “heavy” science. But my reply to that would be that ignorance is no bliss and if one strays from science, they could be vulnerable to many scams of which many of those have been covered on this blog. Some of it looks intimidating but I say this. If you are not yet well versed in science lingo or concepts biology and nutrition, then there is no better time to start than right now. Muscles do not get bigger without use and the same for the brain and understanding. Use it or lose it.
    The “science” does require most focus and concentration and far more time to digest, but after a while, it becomes much faster, easier and you become more proficient. It is worth the effort. Lots of pseudo science in the mainstream media that readers can become wise to, by getting to know real science with references which the mainstream likes to avoid.
    Will, the only thing I might suggest for those intimidated is writing a very simple brief abbreviated summary and then followed by the long detailed article to reinforce your points. Maybe they will not read the detail but at least you have given them an opportunity to do so and help themselves grow as individuals and sharp minds. But for myself, I am most grateful that you take the science so serious. I’d be nervous otherwise. There is safety and protection in knowledge. Its like wearing a shield and armor.

    • Will Brink 7 years ago

      “Will, the only thing I might suggest for those intimidated is writing a very simple brief abbreviated summary and then followed by the long detailed article to reinforce your points.”
      I didn’t write the article Scott, Monica did. She concluded:
      “However, exercise is and always will be necessary. Sorry folks, there are no magic bullets. There’s simply no way around it. Amen!!!”
      Seems like a pretty straight forward conclusion to me! 🙂

      • Scott I 7 years ago

        Well, kudos to Monica! She really waded into the science aspect and I like it. I think people need to exercise their brains and neurons just as they do their muscles. Call it a holistic workout!

        • Monica 7 years ago

          Scott, I’m glad you like my article and approach to writing. And you’re so right, “Use it or lose it” applies to both our muscles and brain cells. Here you got some references that support the importance of intellectual stimulation for building and maintaining the cognitive reserve, which is an important component of successful aging 🙂
          Use it or lose it: environmental enrichment as a means to promote successful cognitive aging.
          Frick KM, Benoit JD.
          ScientificWorldJournal. 2010 Jun 16;10:1129-41.
          Neuroprotective effects of cognitive enrichment.
          Milgram NW, Siwak-Tapp CT, Araujo J, Head E.
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  9. -Derrick 7 years ago

    That was a well-written and (obviously) well-researched article. The length should never be a problem as long as you’re addressing a topic. So for those who prefer not to read all of it due to length, you’re losing out on some valuable information.
    Okay, I’m very glad to see someone address the functions and the influence of the mitochondria. These lil’ energy storehouses have not been given much attention. What they do and how to prevent (premature) death in the cell is very important. It’s great that you discussed the various age-related and diseased states of mitochondria impairment. In terms of fitness, we tend to focus on muscle growth primarily, without taking into account what occurs at the cellular level. Also, age-related macular denegeration helps skin lose its elasticity (read: produce wrinkles), which is why Alpha-lipoic acid and Acety-L-carnitine tend to show a bit of benefit; they address dying mitichondria.
    The questions I have concerns Resveratrol and its association with mitochondrial functioning. Does resveratrol act somewhat like creatine in that it staves off fatigue? Granted, it doesn’t donate phosphate molecules or anything, but it seemed to have done this (stave off fatigue) in lab mice. Also, is the synthesized version (pill) efficacy equal to that of the red wine. On the one hand, can the pill survive the pepsin environment of the stomach, but on the other hand, we must account for the fermentation, heat, storage, and other processes by which wine is made. Last, does resveratrol support against atrophy in non-exercising populations? That is if one exercises regularly wouldn’t proper nutrition along with resistance training (including cardio work) still be required at some point to maintain homeostasis rather than atrophy? Resveratrol alone couldn’t help or could it?
    I welcome yours (Will’s, and anyone else’s) answers. Thanks for a very good article and thanks for pointing out the truth about how ‘exercise mimetics’ can be severely misleading. Much like the current-stimulated exercise belts (great for coma patients though), nothing can take the place of phyical labor (exercise) whereby some physiological pathways must be influenced by resistance and not just a muscle contraction that is artifically stimulated.

    • Monica 7 years ago

      I’m glad the mere length of my articles isn’t scaring away everybody; Will is taking good care of the folks here with shorter attention spans (…wink@ Will), so I’m catering more to those of your who “wanna know it all” (myself included, haha! I get bored whenever I ready anything that doesn’t provide me with enough details needed to understand mechanistic rationales. If the references are missing i get outright mad). 🙂
      The beneficial effects of resveratrol on mitochondrial aspects has not directly to do with ATP production (like creatine, which donates phosphate from CP to ADP to generate ATP), but rather that it activates signaling pathways that are involved in mitochondrial biogenesis. It is the increase in mitochondrial number and/or mitochondrial respiratory chain enzyme activity that could confer performance / endurance enhancing effects.
      While it has been shown that resveratrol helps counteract muscle atrophy in rats, we don’t know if it also does in humans. I don’t recommend relying on a pill for that; again, actual exercise and proper nutrition will always be necessary for any health, performance and longevity pursuit.
      I will answer your questions on resveratrol bioavaliability in an upcoming article (where I will also cover safety and give practical dosage recommendations).

  10. Fairlane 7 years ago

    Love the article and your translations Monica. Now, whenever any of my three sisters ask me, “When are you going to create a Pill so I don’t need exercise” I’ll point them to this post and tell them; no pill like that will ever exist and here’s why”. On the other hand, I shall create nano machines to fully replicate strength and healing and not share it with either of you. MUAHAHAHAHA!! XD

    • Monica 7 years ago

      As long as you make your nano bots chase and beat up all the lazy asses around, I am all for it! 🙂 🙂

  11. Will 7 years ago

    One of the best written articles I’ve read in a long time. Great insight on the potential of these supplements. I’m especially interested in SIRT1 activators. The stressing of exercise as the primary and the supplements as the aids is key. You are not only smoking hot on the outside but your Brain is Delicious. Thanks for helping to always stay motivated to work out, please keep up the great info and inspiration.
    Best Wishes, Will

    • Monica 7 years ago

      Thank you for the compliments. I am glad the length of the article didn’t scare you away. You can find more of my articles (scientifically based and well referenced as always) at

  12. Rick 2 years ago

    Try this one!!! The deeper the color of food??? The deeper the ACSMS(deeper re-active stimuli)!!! Any comment ??? Research done by PRISMS 1968 (McGill University Med. Library).

  13. Rick 2 years ago

    Let me see if i got this right??? Brains, Builded -body, Bodacious, and Befuddling ! No Will ! It is definitely not you!!!

    • Will Brink 2 years ago

      So you don’t find me Befuddling?

  14. Matt 2 years ago

    We are moving more toward a “Brave New World,” with a pill for everything! Thanks for a good article, as always.

    • Rick 2 years ago

      They have! Needles Teas (White, Green, Black), amongst others, have been a miracle pill, or tea sachets for thousands of years. We are still studying 40 years behind the times, even with the most advanced Tech’s. Rick

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