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Irisin: The magic exercise hormone?

Irisin: The magic exercise hormone?
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On January 11 an article was published in the NY Times Health blog section titled, “Exercise hormone may fight obesity and diabetes.”  The article reports on a recently published study in the journal Nature, the abstract of which can be found here.

The authors present research linking a hormone secreted during exercise to the conversion of white fat (white adipose tissue, WAT) to brown fat (brown adipose tissue, BAT).  This is interesting from a scientific perspective because human adults have very little BAT.  By comparison, newborns have modest amounts of BAT — about 5% of body mass, which can protect them from hypothermia, as you’ll see below.  These two types of fat derive their names from how they look under a microscope.  WAT cells look like what you’d think a “fat cell” would look like — a single droplet of fat in a cell and not much else.  By contrast, BAT cells look darker.  Upon further inspection, it seems their darker color results from the presence of mitochondria, the so-called engine of the cell, and other cellular components. Without getting into a lot of detail, a number of investigators believe that BAT is actually closer, embryologically, to muscle than it is to WAT.

Whenever I give talks to swimmers, in particular, I get asked about BAT because the advantage of BAT (over WAT) is that one of its jobs appears to be thermogenesis (heat production).  This is of paramount importance for a hibernating animal and could come in handy in a newborn baby.  It’s also highly desirable, say, for someone trying to swim across the frigid English Channel while staying reasonably warm.  As a result of this thermogenic property of BAT, it’s possible that the more you have the more energy you’d expend. Hence the reason this paper is so interesting and the reason the NY Times is writing about it.

There are two main points I want to make about this article.  I’m not at all “picking on” either the NY Times article or the scientists who did the research.  I think this research is fascinating and well conducted. But, I do want to give you a few things to think about while you get constantly bombarded by articles like this, which appear to be coming at us at an ever increasing frequency.  I think I get about 4 or 5 such articles every week, though there is probably a selection bias somewhere in there, given my interests.

My first point has to do with the concept of relative importance.  To have this discussion I think it’s important to understand the difference between a “first-order term” and, say, a “tenth-order term.”  Anyone who spends enough time with me (e.g., my poor wife) will attest that I always speak about this distinction. Let me illustrate with an example.  If someone is on a sinking ship in the middle of the ocean, the first-order term (or requirement) is finding a lifeboat with oars.  The second-order term is securing an adequate supply of fresh drinking water.  The third-order term is having sufficient food to eat.  The fourth-order term might be finding a map of nearby islands.  And so on.  The tenth-order term, by extension, is having a high quality pair of polarized sunglasses.  I am not suggesting that being on the ocean for days without good sunglasses would be pleasant — it would be miserable — but it’s nowhere near as important as having a boat, water, and food.

It’s become very popular to discuss what I refer to as “tenth-order terms” while ignoring “first-order terms” whenever we talk about obesity research.  I believe this is because the research community (and the journalists who cover it) want to believe that the answer to this overwhelming problem is so complex, which explains nicely why it hasn’t been cracked yet.  How else can the solution be eluding the medical establishment?  We tend to fixate on peptide YY, ghrelin, leptin, and now irisin.  I am not saying these hormones don’t matter, but when we focus on them — at the exclusion of the obvious hormone (insulin) that actually regulates fat accumulation — it’s a real tragedy for the 200 million Americans who are overweight.   Remember, obesity is not a disorder of over-eating or under-moving.  It’s a disorder of fat accumulation.  These are not the same thing at all, as I’ve written about before.

People are frustrated with how difficult it is to lose weight, and rightfully so.  I know I was.  Even this article acknowledges the disconnect between doing what we’re told and reality — “Why, for instance, if exercise increases levels of irisin and irisin increases the body’s stores of energy-burning brown fat, does exercise so rarely produce significant weight loss?

This point has been acknowledged for some time now, too.  The American College of Sports Medicine and the American Heart Association in their physical activity guidelines (2007) made this statement: “It is reasonable to assume that persons with relatively high daily energy expenditures would be less likely to gain weight over time, compared with those who have low energy expenditures. So far, data to support this hypothesis are not particularly compelling.” (And one of the co-authors of this ACSM/AHA report is an exercise physiologist who described himself as “short, fat and bald” when he started running 30 years ago, and since then has run 85,000 miles, or the equivalent of more than three times around the globe at the Equator, while only becoming “short, fatter and balder,” in his own words.)

I know it’s tempting, when we read reports like this, to hope for a magic drug – synthetic irisin – that we can inject into ourselves one day to help us burn more fat.  But the good news is you don’t need synthetic irisin. Or synthetic leptin.  Or some other magic drug. You don’t even need to exercise to lose weight (or fat, more specifically), if you don’t want to (though I think there are at least 5 excellent non-weight-related reasons to do so).  You just need to stop eating the foods that increase insulin levels in your body and retrain your body to burn fat instead of storing it.

Fifty years ago we had a fraction of the obesity and obesity-related diseases we face today.  Was it because we exercised more?  Hard to believe this, given the best available evidence of exercise’s impact on weight.  We certainly didn’t have synthetic irisin or leptin to inject into ourselves.  The reason our society has become more obese and more chronically ill than ever before is because of what we eat.  It seems we should spend more time and energy reversing that (obvious) problem, rather than searching for a magic drug.

My second point is not just a comment on this work but more of a broad comment on much of the obesity-related research being done — it’s often done in mice.  Renato Baserga, an oncology researcher at Thomas Jefferson University, once quipped, “If you cannot cure cancer in mice, you should change careers — it’s so easy to do.”  I think we need to keep this principle in mind beyond oncology.  We should be careful what we infer or extrapolate from mouse studies to humans.  For one thing, mice are natural herbivores, not omnivores, as we are.  To give you an example of this, it is pretty well accepted that feeding a mouse a diet high in animal fat will lead to insulin resistance and, eventually, diabetes.  However, this is not true in humans.  Why?  It’s a good question, and not one to which I claim to know the answer.  I would guess it has to do with our evolved abilities to prioritize fat oxidation in the presence of low insulin levels.  Perhaps mice have not evolved to do this, as a result of their plant-based diet.  The oncology literature is filled with hundreds, if not thousands (literally), of examples of treatments that work in mice, but fail to work in humans.  Mouse research is very important, to be sure, but we need to be mindful of ever assuming that because something is true in mice it’s therefore true in humans.

So what to make of irisin? Well, the authors of this study (in the actual paper, not the NY Times article) comment that “exercise has the capacity to improve metabolic status in obesity and type 2 diabetes, but the mechanisms are poorly understood.”   This point is actually debatable.  It’s true that lifestyle changes (e.g., better nutrition and exercise) can improve the metabolic status in obesity and type 2 diabetes, but it’s not clear that exercise on its own is exerting this effect.  Furthermore, while mouse models show that high amounts of BAT seem to confer resistance to obesity and diabetes, it’s not clear that 1) this is true in humans, and 2) if it proves to be true in humans, that sufficient irisin can be exogenously administered to produce sufficient BAT for the effect.  This research is exciting and deserving of the accolades being bestowed upon it, but we should not lose sight of the bigger issue.

My 2 cents: let’s work harder on changing what we eat, rather than hoping for designer drugs, to fix the epidemics of obesity and diabetes that are hurting so many Americans.  It’s cheaper and will work a whole lot sooner.

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About the Author:

Peter Attia, M.D., is the co-founder and President of the Nutrition Science Initiative (NuSI), a non-profit based in San Diego, CA. He received his B.Sc. from Queen's University in Canada and his M.D. from Stanford Medical School in California. After his surgical residency in general surgery at Johns Hopkins he worked as a consultant at McKinsey & Company. He founded NuSI with scientific journalist Gary Taubes in 2012.

Discussion

  1. Tuck  January 26, 2012

    Animal fat doesn’t make mice fat. Lard stuffed with vegetable fat makes mice fat. Pigs fed lots of grain have the same reaction that humans, mice, or cattle have. They get fat. Pigs and humans concentrate the vegetable fat in their tissue. And if you, or a mouse, eat their grain-stuffed fat, you get fat too…

    Feed a mouse or a human high amounts of fat from grain, and the same thing will happen to each. Do a google search on “omegaven Boston children” and find out what vegetable fats do to mammals in large quantities.

    (reply)
    • Peter Attia  January 26, 2012

      Certainly not disputing that vegetable fat or grain stuffed fat makes various animals fat. The point is to be cautious about inferring something from a mouse model (or other animal model). Sure a pig model is better, but the point is that until something has been demonstrated in humans, we should be cautious.

  2. jake3_14  January 26, 2012

    Hear, hear!

    (reply)
  3. Matt  January 26, 2012

    I like the way you deflate this kind of reporting by highlighting its obsession with “tenth-order terms”. A great expression.

    I think a big part of the reason people fantasize about a solution coming from this kind of research is the psychology of addiction itself. An addict who doesn’t want to quit fantasizes about recovery solutions that can only be realized in some abstract, non-existent possible world. Because he doesn’t really want to change. So your solution is simple but people in the grips of the carbohydrate cycle don’t want to take it, because they can’t imagine a life without bread/sugar. And the only way to get on the other end of that mindset, it seems, is to reduce one’s insulin by not eating the carbohydrates one can’t imagine living without. So you get a kind of bootstraps problem, and it’s much easier to fantasize about a tenth-order solution than it is to face that kind of problem.

    (reply)
    • Peter Attia  January 27, 2012

      Matt, thanks so much for this very cool addition to this idea. I really like and agree with your point. There must be some cognitive dissonance component to this.

    • lorraine  February 29, 2012

      Matt,

      What a great perspective on this. As someone in the trenches daily with obese, diabetic and mood disordered clients, there is truth to what you say.

    • Sumi Allen  July 24, 2012

      Hi,
      I have a comment and sorry i didn’t keep up back this past winter.

      I too am Paleo, I’m fighting this endocrine disorder that puts me at a high risk for diabetes.
      I could care less what you eat, drink or weigh. I run and avoid “processed carbs” aka HIGH FRUCTOSE CORN SYRUP (yes say it out loud you coward)… and my glucose levels were very good. I would much rather run a lot than take glucophage. So Bristol Myers Squibb can suck it. They violated the AMA code of ethics regarding conflicts of interest with the medical community. You all lied and violated the Hippocratic Oath as well.

      They added horrible obstacles to my medical professionals whom I needed when I came down very ill 2 years ago.

      They will never be forgiven. And this is my revenge. You NEVER exploit a sick person in need of help. NEVER.
      How do you look at yourself in the mirror?

      First of all, you lost all credibility that money was spent on your PhD in Medicine. I’m just safely assuming that you have one.

      If you look up PPAR alpha, it’s kind of synonymous with Malonyl CoA that blocks CPT-1 from pulling LCFA into the cell to be oxidized by carnitine. Carnitine is at the center of the fat burning universe. It has been and always will be.

      Matt is right. People do get cravings. I discovered that enhancing my energy levels with amino acids does help with those cravings. So are low GI options in food, will power, etc. The reason why I craved sugar is because my blood glucose was low.

      So what does that mean?

      MY INSULIN LEVELS HAVE BEEN WAY TOO HIGH.

      To appease glucophage maker Bristol Myers Squibb, the endocrinologist will not be testing me for insulin levels.

      Oh btw, you can fix this with inositol, melatonin, arginine and other nutrients.

      ALSO, INFLAMMATION CAUSES INSULIN SPIKES.
      Now, if you really exist -invading my family’s territory with your quackiness… nieve or disgruntled T-reg cells send out TGF-beta which intersects inositol. Now, inositol reduces insulin spikes. When this happens, the follastatin levels go up to aid the activin to increase insulin release.

      ALSO, the l-cells read sugar levels in the digestive tract then release glucagon like peptide-1 to the pancrease to tell it to secrete more insulin.

      High insulin levels cause people to gain weight rapidly. High insulin puts people at risk for breast and prostate cancer because it blocks the IGFBP-1 (IGFBP-1 prevents breast and prostate cancer?)

      And yet another study showed that injecting insulin and taking metformin puts people at a high risk for heart attacks.

      I’m deeply incensed that you’re pushing out incomplete information. Big fat Big Pharma CEOs will be regulating healthcare for diobese Americans. My family has 4 generations rooted in SD, a few with diabetes + complications. I cannot even tell you how put off I am.

      Please Go away.

    • Peter Attia  July 25, 2012

      Sumi, I’m sorry to hear about your struggles and frustrations.

  4. Garth  January 26, 2012

    I think the relative importance distinction is critical. It’s especially frustrating in the context of the blogosphere, because any claim is generally refuted in the comments section by someone saying, “Well, I tried [Atkins, Paleo, Raw, Vegan, Breatharian] and didn’t lose any weight, so your theory is wrong.” The related idea is, “No one diet is perfect for everyone,” which is in turn a close cousin of, “everything in moderation.”

    In my opinion, these statements contain some truth, but are largely misleading. I think there is a wide spectrum of carbohydrate tolerance, particularly in regards to weight – but that doesn’t mean a high carb diet is necessarily healthy for anyone, or at least healthier than a lower carb diet. I’m fascinated by why some people may not respond to a low carb diet. I’m very interested in idiosyncratic n = 1 dietary experiments.

    But in discussing the increase in obesity, metabolic syndrome, type 2 diabetes, etc., these largely serve to distract from the central question. What has changed in the past 30-40 years that could possibly account for the rise in these diseases? The carbohydrate hypothesis is so much more convincing, particularly as laid out by Taubes, than anything else I’ve seen, that I’m stunned it isn’t more widely accepted, or at least more widely viewed as something that urgently needs to be tested as rigorously as possible.

    (reply)
    • Peter Attia  January 27, 2012

      Garth, you say it better than I do. Can you start writing the blog for me? :) Seriously, you are absolutely correct and I’m willing to spend the rest of my life helping people (including doctors and policy makers) understand this. I’ve actually got an entire framework for this idea. I’ll lay it out in the future.

    • David  February 24, 2012

      Garth –

      I think this is an excellent point that receives relatively little attention… I would add that what I see as the greatest challenge in medicine is understanding that variety of the human genome is so broad that there are virtually no one-size-fits-all answers to any non-strictly physiological issues, and until medicine is able to effectively process the huge amounts of data that are necessary to account for this incredibly vast variance, medicine will always be of limited effectiveness. Weight loss is no different.
      I would also add that it seems to me weight loss would perhaps be better served by categorizing the various “influences” to adipose tissue formation and de-formation, and then trying to genetic paradigms that respond most effectively to the the different influences. For example, some people have “high metabolisms” and can eat virtually anything without creating adipose tissue. Others cannot…
      If anyone has thoughts on these subjects I would be interested in hearing them. Thank you!

      David

  5. Jill  January 26, 2012

    The French force feed ducks GRAIN to make the livers fatty. Ages ago I read that butchers didn’t like pork meat from pigs fed too much polyunsaturated fat because the meat was “wet” and sticky.

    (reply)
  6. Stephanie  January 26, 2012

    A couple thoughts after reading the NY times article and the research paper: 1. Brown fat must be triggered and only temporarily expressed during the environmental stimulus (exercise, cold, others?) otherwise, 2. how could it be an adaptive strategy? 3. would be interesting to see data on latitude variation in brown fat quantity in humans, and 4. I wonder if BAT enabled early hominins to populate colder climes.

    (reply)
    • Peter Attia  January 27, 2012

      All great questions, Stephanie. Perhaps an even greater issue is how much WAT can you actually convert to BAT, with all the irisin in the world? Would it/could it be clinically meaningful? My guess is that the variation (e.g., by latitude) is modest, but probably doesn’t account for an enormous difference in basal metabolic rate or free living expenditure. Just a guess, though.

    • Stephanie  January 27, 2012

      I’m actually much more interested in the evolutionary aspect of this biological process whereas the general talk on this research is how it mitigates obesity and metabolic syndrome in (what I think is implied) a modern setting. However, it is not clear to me why such a process of “whole body energy expenditure” would be favorably selected throughout evolution, unless it relates to some sort of historic high energy throughput status of our species. The implications then of whole body energy expenditure in an EEA perceived as resource limited or constrained really throws a wrench in the system. Even the authors can only think of a hypothermia defense explanation. I’m very very curious.

    • Peter Attia  January 27, 2012

      My thoughts on BAT from an evolutionary perspective are also just as it pertains to thermogenesis (hibernation, neonates with high surface area).

  7. Joshua Wardrop  January 26, 2012

    Assuming I’m attempting ketosis, what’s your take on diet sodas, zero carb rockstars, white russians with cream and vodka (nearing 0 carbs), and other such vices?

    Even without carbs/sugars, do you expect some of these things to derail or seriously affect achieving ketosis?

    (reply)
    • Peter Attia  January 27, 2012

      Stay tuned, Joshua. I’ll be writing about substitute sweeteners in the next few weeks.

    • greensleeves  January 28, 2012

      Alcohol always slows ketosis, as the body burns alcohol before fat. Don’t drink if you’re really serious about ketosis.

    • Peter Attia  January 28, 2012

      It’s a fair point, and I think it comes down to how much “ketone buffer” you have. I drink about 2-3 glasses of wine per week and have no trouble staying well into ketosis (i.e., beta-hydroxybutyrate levels in whole blood between 1 and 2 mM) despite this. I would suspect that drinking more would/could inhibit this, though, as most wine is about 4% sugar by weight.

  8. Kevin  January 27, 2012

    “By the way, in the next few weeks I will be writing about why some countries like Japan, Italy, and France were able to historically stay lean, despite eating carbs….you’re already hinting at of the three reasons.”

    I’m very interested in this and look forward to your post.

    Quick question, probably inane. If insulin regulates fat accumulation and if chronically elevated insulin levels lead ex hypothesi to obesity, why are there no obese fruitarians?

    Thanks in advance.

    Best,
    Kevin

    (reply)
    • Peter Attia  January 27, 2012

      Stay tuned…it will be addressed, in effect, withing the broader context of the post you allude to. Hint: dose response.

    • Troy Leitzsey  January 28, 2012

      I’ve read anecdotes at the 30-Bananas-A-Day (low fat fruitarian) forum about individuals who can’t seem to lose all of their unwanted body fat. Of course, unless one can conduct carefully controlled trials, how does one actually prove that someone who calls his/herself fruitarian is following an agreed upon definition of the diet. Much like veganism, there are those who cheat in private. There are Coca-Cola and processed food vegans as well as RAVE Diet (or Ornish, Esselstyn, etc.) vegans. Thus the broad suggestion that “fruitarians” do not get obese or overweight may not prove valid, and we haven’t even considered possible causes of mortality due to probable malnutrition on such restrictive diets. Just my two cents. :)

    • Peter Attia  January 28, 2012

      Yes, we desperately need controlled clinical trails. Uncontrolled or observational trials provide little value.

  9. RoseAnne  January 27, 2012

    Thank you for so clearly outlining the difference between research on mice vs human research. I agree whole-heartedly.

    Despite that possible difference I admit to finding the research very interesting. However after reading the article in the NYT and in a couple of other publications I felt completely frustrated. Once again the “results” were hailed as opening up the possibility of a new drug to treat obesity, instead of using the information to encourage people to get off the couch. I often wonder if many maladies from obesity to cancer would not have been virtually eliminated if we focused truly on finding the healthful way to live rather than on developing a pill that will literally allow us to have our cake and eat it too.

    (reply)
    • Peter Attia  January 27, 2012

      RoseAnne, you hit the nail on the head. Yes, the research is interesting and noteworthy, but we’re missing the big picture. Should we be using this research to myopically focus on designer drugs? Or should we fix the existing problems with what we already know?

  10. Saj  January 27, 2012

    Great blog! (Found it through the blog of Taubes, whose book opened my eyes) Keep up the good work!

    (reply)
  11. Barbara Hvilivitzky  January 27, 2012

    Peter, we’re all so HUNGRY for information!!! You poor kid!! You’re going to be busier than a one-armed paper hanger!! As you have learned already….But seriously, I’ve just learned from reading here two things:

    1) I need to build some muscle even at my age (66 yo female) in order to raise metabolism to burn more fat,

    2) the reason low-carb diets don’t work for some who try them is they don’t really do it seriously ( I know that sounds unking but I’ve had long experience reading on forums and the first thing that happens it that they “tweak” and “cheat” and become impatient) and this MUST be taken seriously or NO fat loss happens that can be sustained.

    So off to get the weights out of the basement and will start some basics. Thanks for all you are doing.

    (reply)
    • Peter Attia  January 27, 2012

      Barbara, I’m not sure building muscle to raise your metabolism is the right reason. In fact, it probably plays a small-ish role. The reason to build muscle (and I fully concur with your decision to do so) has more to do aging well (e.g., preventing injuries, maintaining your ability to carry out your daily activities). Keep up the good work.

  12. Greg  January 28, 2012

    I’m also an endurance athlete (runner), who slowly put on weight over the years. In retrospect, I now blame the popular misconception of the need for a high carb diet. Since this past spring I’ve moved completely away from refined carbs, sugars, and moved to a higher fat/protein diet. I’ve lost weight and my vitals are improved (e.g. blood pressure).
    Additionally, I am fascinated by the work that you and Taubes are doing with regard to the larger nutritional discourses. I am working on a social science Ph D, and in the future I hope to study the disputed narratives of obesity science from the perspective of science, technology, and society (STS) literature. There are many fascinating and overlapping levels of the social and cultural, particularly as they intersect with networks of power and various actors who have ideological positions framed from essentialist identity positions.

    Great work.

    G

    (reply)
    • Peter Attia  January 28, 2012

      Greg, thanks for sharing your experience. Gary and I are really excited about what can be done with respect to policy change and re-education if enough people get behind it and we’re thoughtful about fixing the science. Hopefully there will be a way to work together on this problem one day.

    • Greg  January 29, 2012

      BTW
      beyond the academic interest, as a marathoner/ultra-marathoner, I am interested on your take on what to eat “before”, “during” and “after” an event or training session, based on metabolic science. I’m under the impression that I can get away with simple sugars during and perhaps just after an event. Also–what is your take on caffeine/coffee?

      Best,

      G

    • Peter Attia  January 29, 2012

      We should separate “getting away with” things from “optimal performance” and “thriving.” A lot of people get away will lousy eating habits, and even succeed despite them. What we should aspire to is being at our best. I’ll write about this in the future, for sure. I’m a fan of caffeine, but really that’s because I love coffee (great excuse to drink more fat in the form of cream), and I don’t trust de-caff. Also, we do know that caffeine does speed up fat mobilization through up-regulation of hormone specific lipase (HSL).

    • Corey R. Wardrop  January 29, 2012

      Greg,

      I’m sure you’ve seen Dr. Lustig’s video (“Sugar: The Bitter Truth”, posted previously by Dr. Attia). It’s amazing to me how politicians can ruin a nation with ‘good intentions’.

    • Greg  January 30, 2012

      Corey–
      Yes, that is one great video. I’ve recommended it to a lot of people.

    • Greg  January 30, 2012

      Peter,

      I didn’t mean to come across as wanting to “get away” with sugar consumption as a side benefit of endurance activities. I am just wondering if there is still a time/place for a limited “hit” of sugar for performance. That said, it looks as if you have done a lot of research on yourself with regard to performance on a carbohydrate-restricted diet, with seemingly impressive results.

      That said, I am only wondering if there is still a place for small and limited amounts of sugar during high intensity events; purely for the purposes of performance, and without any negative impact on the insulin production/reaction system as the sugars are immediately metabolized (probably a huge oversimplification here).

      Believe me, I don’t particularly like choking down a GU during a marathon, but it seems necessary. It is interesting to note that during longer races–50k, 50 mile, 100 mile, I have tended to eat a higher percentage of my calories from fat (not sugar). But the pace is much slower, and I’ve always assumed that I’ve been able to rely more on fat for energy during these races.

      G

    • Peter Attia  January 30, 2012

      Greg, I think it really depends on what you’re training for. I have a friend who is an Olympic swimmer – his entire athletic world comes down to a race less than one minute long. I’ve helped him modify his diet quite a bit, and we still don’t use any sucrose or HFCS. That said, he is (of course) not in ketosis and probably consumes about 200-250 gm/day of carbs, but we’re very careful with which ones he consumes. He does us about 50-100 gm of superstarch, alone.

      For someone who is highly dependent on sugar, the abrupt removal may cost a bit of performance, but once you adapt to less sugar, I think you’ll more than make up for it. Again — not necessarily be entering ketosis, but by being more mindful of which carbs you do choose to consume.

  13. Robby Hanna  January 28, 2012

    Hi Peter,

    I was going to email you, but your contact page requested to instead post questions on your blog:

    Have you ever practiced fasting? I’m curious about your opinion on fasting (only water), so please share.

    Thanks!

    (reply)
    • Peter Attia  January 28, 2012

      Robby, the only time I fast is when I’m “stuck.” For example, sometimes when I’m traveling and can’t find anything “safe” to eat, I’d rather eat little than take a chance. I know many have advocated for temporary fasts to break through plateaus. It may work, but I suspect it would have a lower efficacy on someone is ketotic at baseline. Of course, for me fasting for, say, 8 hours is probably less uncomfortable than it is for someone dependent on carbs, as my brain is already feeding off beta-hydroxybutyrate and my body is already converting fat to ketones.

    • Robby Hanna  January 29, 2012

      Peter, I enjoy your thoughts presented on this blog and thank you for kindly answering my previous question. I’m also glad you’re athletic and lead an active, physically competitive life, as that is a central part of my preferred well being, even at 50.

      I’ve found truths from experience that supports your answer to my question.

      My expertise has been earned throughout a decade of fasting in all possible ranges, from 28 days all the way down to skipping meals, as you suggested. I’ve found significant differences and varied benefits throughout these diverse fasting choices, and you’re correct that once ketotic at baseline it’s not necessary to fast. However, I’ve found that fasting can help increase top-end power gains for athletic output once achieving and sustaining a ketosis fueled athletic performance.

      I also find fasting is a great way turbo accelerate ketosis comfort and stay there, especially when trying to help others leave their insulin based metabolism: the resulting effects of palate cleansing makes it way easier to adhere to low carb and high fat diet shifts than a more gradual introduction with restriction of carbs–the sugar cravings are too great and bad food choices immediately referable. Fasting creates a nice memory gulf, taste bud reset and immediate appetite love for fats.

      Since we share a pursuit of athletic performance, have you researched any fasting used by bodybuilders as a way to rapidly amp up muscle gains?

      Here’s just a couple:

      Martin Berkhan
      http://www.leangains.com/

      and Brad Pilon
      http://www.eatstopeat.com/999.html

      They have unique approaches which you might find interesting. I’d appreciate any thoughts on this and would welcome your opinions on other helpful onramps to superior athletic performance and optimal health.

      Thanks again,
      Robby

      PS I really want to get that “Praise the Lard” t-shirt you were wearing. Where can I order it?

    • Peter Attia  January 29, 2012

      Hi Robby, Thanks so much for passing along this information. Since I’m not a bodybuilder I actually haven’t spent much time exploring their techniques. However, given how much attention they pay to their bodies, I’m sure there would be a lot of interesting information to be gleaned. I’ll check this out. I get asked about this shirt all the time. It was given to me as a gift once when I was giving a talk. Not sure where they got it. Sorry…

    • AGS  February 29, 2012

      Where can I buy a cool Praise the Lard T-shirt?

      Currently, you can only purchase one of our famous original Praise the Lard t-shirts at the San Francisco Ferry Building. That should change in early 2012.

      source – http://prmeatco.com/about-us/faq/

    • Jan James  January 30, 2012

      Just a comment, I’m no athlete but have stayed on a low carb diet for 4 years to keep my T2 diabetes under control (and it works superbly). I often have to remind myself to eat because I really don’t get hungry. Before, I would find myself constantly in the kitchen, mindlessly wandering around and looking for something to stick in my mouth. I occasionally fast for a day or two to get a baseline on my blood sugar. I once fasted for 8 days, it was no big deal but I didn’t lose a pound. Not one.

    • Peter Attia  January 30, 2012

      Jan, as you’ve observed the problem with starvation is that our body is pretty wise to it…and we greatly reduce our metabolic rate. I wonder if you were already in a state of ketosis when you embarked on the fast?

  14. Corey R. Wardrop  January 29, 2012

    Dr. Attia,

    I’ve taken your advice and started a ketosis diet about a week ago. At 30 years old, my body composition is just about what yours was when you started. I’m in decent shape now, but certainly not where I want to be. My girlfriend is a (beautiful) carbaholic and thinks I’m nuts, but what you’ve written makes a lot of sense.

    Let the war begin.

    P.S.- I voted for your blog on the contest. Good luck!

    (reply)
    • Peter Attia  January 29, 2012

      Thanks very much, Corey. Since you’re already on the path (ahead of my ability to write about in great detail), please check out The Art and Science of Low Carb Living by Phinney and Volek. It’s going to be a valuable tool for you.

    • Corey R. Wardrop  January 29, 2012

      Your “What Do I Eat” jpg became my shopping list. I’ll definitely pick up that book, thanks!

    • Peter Attia  January 30, 2012

      Corey, just remember that what I eat is just that…it’s all about understanding where you’re at, and where you’re trying to get. Glad my list can give you some ideas, but don’t mistake what I say as the only way to make it work.

    • Guillaume Belanger  January 31, 2012

      Hi,

      Firstly, I am very happy that you have joined forces with Gary to change the world and make it a better, healthier place for all. It is very commendable and share in that in effort. I loved Good Calories, Bad Calories, and even though I didn’t learn much from it since I had already been reading on the subject for about 4 years, I certainly gained an appreciation for the actual history of how this process of transforming an entire nation, and to some extent the whole western world, into fat and diabetic carb addicts played itself out.

      Secondly, I would like to point to Ron Rosedale’s work that is what turned me onto a carb-less, moderate-protein and high-fat diet. He has recently engaged in a debate with Paul Jaminet who advocates eating safe starches like rice and potatoes, which I, just as Rosedale, think is absurd.

      Thirdly, after more than 4 years on this very low carb diet with many refinements along the way, I totally agree with you that it is really important to distinguish the essential (lower insulin) from the superfluous (WAT and BAT). However, it is also important not to get stuck there, because there is a whole wide world of refinements and adjustments to make to actually achieve optimal health, in particular through optimal digestion.

      For the good of all who are interested in optimal health, I have also written a few articles relating to health in the context of physiological considerations, (including my first post , that might be of interest to Corey who is just starting and looking for inspiration for his shopping list). I do not post very often, maybe once per month, but I think that the posts are definitely worth reading. I would be happy to have you follow my blog as I follow yours, and very happy to hear what you have to say about what I write and have already written.

      Thanks for all the work and effort you put into this.
      Guillaume

    • Peter Attia  February 1, 2012

      Hi Guillaume, thanks so much for your comments and insights. And thanks so much for sharing your own information for me and others, looks like some great resources. I’m glad you appreciate the “art” of optimization and the importance of starting with first-order terms and moving to nth-order terms. Finally, I don’t know Dr. Rosedale personally, but hopefully our paths will cross soon.

  15. Barbara Hvilivitzky  January 31, 2012

    Peter, I find it a bit difficult to keep calories reasonable when I try to increase fat. I aim to eat around 60 grams of protein daily. I don’t think I need much more than that. When I try to get fat to make up 75-80% of what I eat to get into ketosis, and that 60 grams of protein about 10%, the total calories shoot right up. Carbs would be the rest. I’m trying to follow your lead in general by upping fat and keeping protein in check but it sure is hard at the lower calorie level!! Any advice?

    (reply)
    • Peter Attia  February 1, 2012

      Barbara, no need to count calories. Eat when you’re hungry, stop eating when you’re not. The whole goal is not to count calories, and for those no in ketosis (where you need to be mindful of protein and very restrictive of carbs), not to count anything at all.

  16. Guillaume Belanger  February 1, 2012

    Hi again Peter,

    Ron Rosedale is probably one of the first medical doctors to have really understood the insulin mechanism and importance of carbohydrate restriction for health and longevity. His article (conference transcript) entitled Insulin and its Metabolic Effects presented in Boulder in 1999, together with Mary Enig’s The Skynny on Fats, are the two articles that changed my life from on day to the next.

    Although it has been known since the 1800s that carbohydrate restriction is the most effective way to loose weight, control or cure diabetes, and regain health in general, as we learnt in Good Calories, Bad Calories, this knowledge was largely lost starting in the middle of the 20th century. Ron Rosedale is one of the scientists and medical doctors that has been at the forefront of insulin research for several decades now, and one of the pioneers in renewing and spreading interest in the importance of carbohydrate restriction, especially in the treatment of diabetes and metabolic disorders, his professional specialty, through his own medical practice as well as through articles and talks. I have to say that I did find it somewhat surprising that Gary did not mention Rosedale in his book. In any case, here is a list of his articles and things from his own website: http://www.drrosedale.com/rosedale_writing.htm

    Ciao
    Guillaume

    P.S. Could you please fix the hyperlink in my previous comment: I forgot to close the html tag and the entire paragraph appears as a hyperlink instead of just the words “my first post”. I also sincerely hope you will find the time in your busy schedule to read and comment on my articles on http://healthfully.wordpress.com either on the blog or directly to me be email.

    (reply)
    • Peter Attia  February 1, 2012

      Link fixed. I’ll try to connect with Ron. Hopefully meet up in person.

  17. Sexy Jane  February 16, 2012

    Peter Attia, excuse me if this is a bit off topic, but… This makes just about anyone upset: Diets actually lead you to gain pounds in time and that has turned out to be more and more apparent in the excessive weight epidemic that’s negatively effecting this kind of unhealthy food, nominal physical
    exercise era. Are you aware that arena seats really need to be increased to support the increase in peoples increasing, ahem…girth? It implies that we are now transforming into a bigger country (and by no means in any great way) individuals than all of us have ever have prior to now and that is essentially previously two full decades alone. Our kids are afflicted with overweight associated conditions for instance diabetes in addition to heart problems.

    Someone said that during a research project seventy obese American young children inside the age range of six to 19 have been subjected to many battery of medical tests to observe the consequence that the food intake rich in fats had on the youthful physiques. The outcomes ended up being eye opening. All was cursed with high cholesterol levels as well as were inside the high-risk group of getting coronary disease and coronary heart failure which some patients ended up already exhibiting warning signs of.

    Could there really be any kind of a cure for anybody? I contemplate your answer should be indeed. Apparently pretty much all we end up needing is plenty of exercise and diet. We pretty much all have to get started with doing it Today!

    (reply)
  18. Birgit  February 24, 2012

    I love the “concept of relative importance”, will have to steal that term when dealing with my teenage daughter, LOL.
    I am curious how you would rank food issues in importance other than insulin, esp. these:
    avoiding modern wheat (as discussed in “Wheatbelly” )even for people not ready to go low-carb; avoiding non-organic food, especially animal fat that is not organic and has higher concentrations of toxins that are endocrine disruptors; along with it the question if it would help to eat a low-carb diet that is plant-based to avoid toxins and to consume more phytonutrients that may protect against cancer
    This last issue came to my attention after watching this video-clip on NutritionFacts.org:
    http://nutritionfacts.org/videos/plant-based-atkins-diet/
    I’ve been eating low-carb (60-70 grams/day) for 1 week now and am excited to say that my running, even though very slow, was much better than 2 days ago, could have kept going forever and strangely enough a pulse of 138 felt like 130 over all 5 miles. :)

    (reply)
    • Peter Attia  February 24, 2012

      Birgit, you’re asking the million dollar question my friends and family ask me every day. If I had a simple answer I would share it. It really varies by person and individual susceptibilities. I do think insulin reduction comes first. I think minimizing omega-6 comes second. I think one needs to be very careful of assuming the label “organic” is magical — sometimes it minimally different from non-organic. Certainly, all things equal you’re better off eating grass fed than grain fed, but really that’s already accounted for in effort to reduce omega-6. One day I hope to have a top 10 list of ordered priorities.

    • Birgit  February 25, 2012

      Peter, that’s an honest answer which is often hard to get these days. :)
      I think you are right that a lot depends on individual susceptibility. Organic is not always superior or necessary. I like buying local when I can so I know how the animals I eat were raised and what kind of pasture they were on (not sprayed with herbicides or in the neighborhood of heavy industry). Having had cancer several times (last time 15 years ago) and being borderline hypothyroid gives me less margin in some ways so I try to get lots of raw veggies in if I can to help my immune system out.
      I’m looking forward to the upcoming paleo summit by underground wellness to learn more about all this.
      Birgit

  19. lorraine  July 29, 2012

    This is a great presentation by Bruce Spiegelman, IMO, of the work that’s been done leading up to irisin, presented last month at the ADA 72nd Scientific Sessions in Philly. I thought you’d be interested in viewing it.

    http://professional.diabetes.org/Adv_SearchResult.aspx?typ=10&sr=adv&cgr=183&tit=&spk=spiegelman&ses=&kwd=

    (reply)
  20. whisperingsage  January 4, 2013

    Weston Price did this study on humans in the 1930’s. He discovered that the healthiest tribes all over the world ate a high animal protien and fat diet. They had fewer cavities, lived longer, had better skeletal development, better birthing outcomes, broader faces, all their teeth, no heart disease kidney disease, diabetes, or any other degenerative disease. His study is available as a book called Nutrition and Physical Degeneration. His website is http://www.westonaprice.org.

    (reply)
  21. Sherwood  February 18, 2013

    I live in central Alberta, Canada. During much of my life, I have been outside all day at very cold temperatures. I know that 10F in November is butt-chilling cold. And that same temp in January is put on a windbreaker and a toque.

    (One expedition into Willmore Wilderness during the Christmas Break saw the rum freeze solid by 9 p.m. New Year’s evening. That same trip saw the invention of ‘bacon buddies’ for breakfast:
    Fry a quarter pound of bacon in the bottom of a pot. Do NOT over cook. It must still be limp, no sign of crisp. Move the bacon aside, and place two halved bagels face down in the grease. Keep turning them to let the air escape. Make a sandwich from the grease soaked bagels and the bacon. I get heartburn just thinking about it now. At -40 they are wonderful.)

    (reply)
  22. Ian  May 28, 2013

    Good article, and glad that you gave your honest, two cents on the studies and studies prior. I completely agree with you that we, as a nation have to look at ourselves in the mirror and face the truths about obesity. It’s not a pill, it’s not an injection, it’s not getting your stomach smaller, it’s about eating the right foods and staying active. Being a personal trainer, I see hundreds of people come to me looking for the fastest, easiest, and quickest way to lose weight. The reality is, there isn’t one. It’s a long, struggle filled process that has many ups and down. But, if they want to be around to see their kids grow, see their next 10 years, it’s the only way to go.

    To me, these research studies might benefit bodybuilders or physique models looking for ways to get leaner and understand their bodies more in depth. Understanding how hormones can literally shed off pounds is important for everyone, but the ins and outs that include, leptin, irisin, and insulin production, to me are more focused on a niche. Thanks for your article, very much appreciated and enjoyed your opinion!

    (reply)
  23. Jeff Johnson  May 28, 2013

    Where is my picture…?

    If you want an image to show up in your posts – the little square box – go to gravatar.com and upload any image you like – crop it – if want your mug to be seen well – this takes all of about five min………

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  24. Tim Claason  March 13, 2014

    ” It’s true that lifestyle changes (e.g., better nutrition and exercise) can improve the metabolic status in obesity and type 2 diabetes, but it’s not clear that exercise on its own is exerting this effect”

    I’ve see a lot of references to studies like the following (obviously, there are other studies like this):
    http://www.ncbi.nlm.nih.gov/pubmed/19124513

    The study claims “Moderate-intensity aerobic exercise, such as brisk walking, decreases IGF-I and IGFBP-3. The exercise-induced decreases in IGF may mediate the observed association between higher levels of physical activity and improved survival in women diagnosed with breast cancer”

    I also read people referencing a study (http://www.ijbnpa.org/content/10/1/10) that supposedly claims 60 minutes of intense cardio exercise can reduce insulin resistance 25% and 120 minutes of intense cardio exercise can reduce it by 50%.

    I understand your claim that “it’s not clear that exercise on its own is exerting this effect”, but it seems to me this statement downplays the value of exercise. Assuming exercise has an insulin-like effect on the body, doesn’t it stand to reason (all things being equal) metabolism would be effected by this?

    Again…sorry about the very late comment on this article..

    (reply)
    • Vicente  March 14, 2014

      Hi Tim,
      my thoughts:
      1) An observational study says that academic results of the students are related to the amount of books you can find in their homes. So, it is that easy: fill your house with books and your children will get straight “A”s!
      The same observational study says watching TV is also positively related to good academic results, so…

      Your second link is about an observational study. Even if you already get it, you can read this interesting article from G. Taubes:
      http://www.nytimes.com/2007/09/16/magazine/16epidemiology-t.html?pagewanted=all
      (this article is linked elsewhere in this blog)

      2) I can’t tell the relative importance of the results they get in the study of your first link. They say that their results MAY explain a relationship OBSERVED… So, I think the authors don’t know either.

      PD: the observational study I talked about is “Factores que afectan el rendimiento académico en la educación primaria” (factors that affect academic performance in elementary education”

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