Currently viewing the tag: "BAT"

Mitochondrial AnarchyHe’s back.  Well, actually I never went anywhere, but it’s been a few months since I added to the blog.  In the mean time hundreds of pounds were lost by people I worked with directly, an invited commentary was submitted to a journal, and I have performed dozens of calorimetry, blood sugar, and food experiments.

Sometimes it’s necessary to isolate from all the bias and do the boring thinking part.  It’s far easier to hype, but at the root of all innovations is a break from status quo.  Like trucks drafting on the highway, it’s quite easy to get sucked into the popular dogma to avoid slamming into the guardrails.

My mentor in innovation, aviation rebel Burt Rutan, says you have to have “confidence in nonsense” to innovate.  That doesn’t mean that every nonsensical idea represents brilliance, but there is a certain break with the masses that occurs with each innovation.  In addition to crazy ideas (we can find a lot of those out there), one must measure carefully and that is the boring part, but I LOVE it. I also like old books, because they give one a much more grounded view of how our current ideas evolved and sometimes it’s easier to see the forks in the road that lead to the current (obviously wrong) idea about eating by stepping back and working your way through it.  If you love history and musty, stained books, then it’s really a joy to do it.

History not reflected, repeats.

There’s been a lot of ground covered in the nearly three years I have been blogging and it’s exciting just how much more research is coming out every year. So many people are doing great work.  I have much more on metabolism and the macronutrient shuffle, but I’d like to cover some new work that published over the last year and a few papers have been meaning to cover for some time.

Since it’s been a while since I last posted (yikes!) or you are visiting for the first time, let’s digest a few bits before going into the main topic. What I want you to know at the highest level is food, or fuel, is THE reason people fight obesity and many chronic diseases.  Further, I think macronutrient labels (protein, carbohydrate and fat) are  meaningless when discussing food, eating schemes or meals.  Exercise is incredibly beneficial with increasing performance and many health biomarkers, but it’s not the fastest way to lose body fat and can significantly impede weight loss.

Your metabolism isn’t broken or low – in fact it scales (gets larger), as does lean mass, with weight.  Hitting the gym to put on lean mass to burn calories and ramp the metabolism isn’t necessarily the solution.  If lean mass was the only thing needed to lose weight then why do bodybuilders or football players ever get fat? They certainly both have more lean mass than I or Aunt ethel will ever have. You know what?

You can’t out exercise your mouth.

It’s food. It is what they eat not how they burn it.  I didn’t say don’t go to the gym nor am I attacking bodybuilding or football, but I want to disconnect those activities from the notion that people are overweight because they aren’t “active” enough or don’t have enough “lean mass” to melt the fat away. It simply isn’t true and for the most part, exercise nowhere near as an effective way to lose weight as diet – especially for people with 50+ lbs to lose.  I am  not implying that there aren’t ways to boost metabolism, but what your diet has a much larger effect on the outcome.

For the last year,  I  had the luxury of measuring  many situations and conditions in a home metabolic lab. There is a seemingly unending list of myths I once believed, things that are repeated as fact in everyday conversation, which are not consistent with what I see in the lab or the peer reviewed literature.  It’s humbling and frustrating all at the same time.  Some of you see this and many more don’t, but anyone that carefully measures would come to similar conclusions. Part of the problem is the monolithic, group-think that seems to infect the fitness/diet community. Certainly the medical community isn’t immune.   I was as guilty as the next.

I’ve heard it said that a generalist is one that knows less and less about more and more until they know nothing about everything and a specialist is one that that knows more and more about less and less until they know everything about nothing. We have a lot of generalists and specialists parading dogma despite unprecedented understanding about how our body works.   I’ve reflected a bit on just how this happens and perhaps we can use it as a sub theme for today’s post.

In the northern hemisphere it is fall, and this is now ABSOLUTELY one of my favorite times of the year.  This is biologically a period  running up to winter’s conservation.  It’s a time when our metabolic system becomes stressed and will rebound with vigor in the spring. This is analogous to muscle hypertrophy in response to the biological stress of lifting a weight.  The overall endocrine system is not stressed by excessive nutrition; it’s stressed by caloric restriction and there is 70 years of data to support this hypothesis.

Every organism tested, from yeast to mammals, lives longer (40-50%) when Calories are restricted typically ~15-30% (up to 25-60%)  of normal for that species (1-3).  The ideal notion is to supply sufficient nutrition with minimum Calories.  Note: you don’t get life bonus points and extra Calories to eat by purposefully concentrating biologically active compounds [insert supplements] and ingesting them in huge doses not found in nature – health doesn’t come in a pill or powder. Chronic overnutrition isn’t solved with more food or nutrients. For over 150 years nutrient content is the catch-all buzz to market excess food.

This idea of Calorie restriction should invoke a similar curiosity in everyone:  if one continually restricts calories by 15-30% of normal, shouldn’t  a point of diminishing return eventually be reached?  In other words, if  a certain number of calories are “necessary” to maintain a person or organism, restriction below that number for a lifetime should  eventually catch up.  Can one truly be in “deficit” forever? Let’s not ask politicians; after all Lavoisier got decapitated for meddling in such political nonsense.  It’s still an interesting question: how much is enough food?

Creating Permanent Change

Over the last 5 years I took a decidedly different approach to the problem from the proceeding 20+ years of relative “failure;” I couldn’t control my weight and had biomarkers inching in the wrong direction.  Looking back now, especially after spending the last few months on a journal manuscript, countless self-experiments, and coaching dozens to success, I can summarize my perspective by offering  a simple shift in two questions that drove all of this work.

1) How do I lose weight -> Why do I gain weight? 

2) What do I eat? -> How is the food I eat processed?

While these might appear to be nearly identical questions, it turns out they are extremely different questions and the answers cause conflicts with many popular “schemes” about food and metabolism.  With that, let’s segue to one area of metabolism you absolutely can have a dramatic impact on even at the cellular level.

Power Plants and Fuel

mitochondrial activity can be compared to a rocket engine.  Fuel is combined with an oxidizer to create metabolic waste products and heat. We all know that in order for an engine to run an oxidizer and fuel must be supplied. The reaction creates new products and typically a lot of extra heat.  When the Space Shuttle Main Engine used to fire, hydrogen (fuel) and oxygen (oxidizer) were combined to make water and obvious extra heat.

The hydrogen and oxygen fuel/oxidizer were contained in the large External Tank in the center.  The solid rocket boosters (on each side of the ET) used Aluminum for fuel and ammonium perchlorate for oxidizer. I think it is fascinating to think that the same basic chemistry of a rocket engine is used by the power plant of cells, the mitochondrion, deliver energy to live and move.

The mitochondrion can be equated to a rocket engine - fuel and oxidizer are combined to create ATP and waste heatInstead of rocket fuel, hydrogen, mitochondria use amino acids, monosaccharides, fats, and alcohol for fuel. Combined  with atmospheric oxygen, they oxidizer,  they produces ATP + waste heat.  The waste heat is managed and that is what maintains our temperature – we are designed to live in environments cooler than body temperature in order to dissipate this excess heat.  ATP is the currency of energy in the cell and you can learn more if you want in this tutorial at Kahn Academy.

I am only dealing with FAT/CHO in the graphic, because ultimately the fate of the other macronutrients (amino acids/alcohol) end up inserting into the CHO pathway.  Later we’ll clear up some of the many myths of ingested versus endogenous sources, but suffice it to say one doesn’t store alcohol (in coolers doesn’t count).  Breaking down of tissues for either indispensable amino acid stores or back up energy is not as common as portrayed as it is easily avoided with even modest amounts of ingested whole-food Calorie.

So we have a fuel currency and everyone wants to believe the obesity “problem” is a simple macronutrient ratio. We hear it’s fat. No, it’s protein. No, it’s carbohydrate.   The  truth is that we all simply “eat” too much. Chronic overnutrition is THE problem, because  in the real world, Calories are scarce.  That is why I find the mitochondrion and mild cold stress so fascinating.  These are inextricably linked and our biology has provided a way to not only recycle that waste engine heat, much like the heater in your car, but in certain situations stop producing ATP altogether and just create heat.

What is even more fascinating is that while BAT seems to get the center stage in the press, every mitochondrion in your body has the ability to play in this ATP/heat exchange. It turns out that mitochondria even have their own DNA – separate from the genes that make you, “you.”  In the last few years, scientist have been toying on the edge of some incredible work that addresses a certain mitochondrial DNA diseases (4), and  you can explore that more  here and here.   I’m not thinking about jumping into mitochondrial DNA modifications at the moment, but it is important to ponder just how independent these tiny power plants are and consider the overall coordination involved in them working in unity.

With the exception of red blood cells,  all your cells contain these powerplants and they are not only at the center of this waste heat production I’m always tapping into, but also at the very root of aging.   What seems paradoxical is that caloric restriction actually increases mitochondrial biogenesis (formation of new mitochondrion); that’s  more power plants created on a diet of less fuel.  Overall, the point to keep in mind is that each mitochondrion decides: 1) what fuel to use based on a host of coordinated signalling, 2) whether or not to produce ATP, and 3) is capable of generating an enormous amount of heat.

Record Breaking Wisdom

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Wim Hof Breaks World Record for Remeha Sponsor.
October 18, 2013.

A little over a  week ago Wim Hof broke  another world record – one hour and 53 minutes in direct contact with ice.  He’s demonstrated numerous time this ability and although it’s been shown that he can generate up to 5 times the amount of heat of younger, healthy (untrained men) he would be the first to humbly say, anyone can do this.   He in fact has trained many people to adapt to mild cold stress and today we will look at science that backs up his claims.

There are numerous other medical benefits, but let’s move beyond. I think it is funny to note that when I visited him last during a Netherlands winter, he always reached for a jacket when we went for walks or to the grocery store and we laughed at the fact I just threw on a pair of gloves and a hat. The iceman has a coat.

Now, I am not trying to imply I can take him on in dueling cold, but wish to point out we all have these habits.  Today, I will give you a few things to change as winter approaches that will tweak these habits and help you adapt. Back to mitochondrial response to cold shock.  The first thing to recognize is that these responses happen at the cellular level.  Each cell is it’s own little domain, and although coordinated and affected by overall endocrine activity, they have the power to bypass ATP production in defense of cold shock (5).  Next is to understand that heat generation not limited to the mitochondria in BAT. Every mitochondrion contributes via the normal cellular activity resulting in  80% waste heat, but further, they can all take it up a notch and give us the the extra 20% in heat instead of ATP.

Adapting the cool approach

In 2008, researchers demonstrated that muscle cells also contribute significantly to adaptive thermogenesis. (6). In this study 11 lean men were tested at 22C and 16C inside a respiration chamber (a whole room indirect caloriemeter).  Even though activity actually fell during the period of mild cold stress, total daily energy expenditure (TDEE) increased.  After a baseline measurement of 34 hours at 22C, they were measured for 84 hours at 16C (60F).  This temperature was picked so as to not induce shivering.

Qualitatively, it happens to be exactly the temperature I find that the most people can tolerate with little period of adaptation. A biopsy from  leg muscle (M. vastus lateralis), was taken after each test period and later analyzed for mitochondrial uncoupling.  Those results clearly demonstrate it is present.  The authors also note that epinephrine  has been reported to increase total body energy expenditure of up to 40%.   What this means is that whether you have BAT or not, you can still adapt and create non-shivering heat.  Not only that, but it’s more energetically favorable to skip the ATP step (shivering/exercise) and just dump the high-calorie stored fuel (FAT) directly to heat.

We learned in A New Eye on BAT, that Irisin produced in a response to exercise promoted the “browning” of white adipose tissue and caused them to join the Muscle/BAT heat game.   The puzzling paradox was that of a tissue encouraged to “waste” energy by producing heat as a response to increased activity.  At first, these two actions would appear to conflict: excess activity causes tissue to be formed, which in turn creates 100% waste heat instead of ATP involved in cellular activity and survival.   As examined from the larger perspective it seems like an energy death spiral, but if exercise is viewed as a modern day mimic of shivering, this is a more effective way to keep the body warm – i.e. it conserves energy.

Even though exercise and shivering are primarily an activity of high respiratory quotients (i.e. glycogen/CHO, not FAT), the body does have a system to efficiently adapt to a dense fuel source (FAT) without the deleterious tissue breakdown associated with prolonged/intense muscular activity. Earlier this year, two related  research projects showed up.

The first looked at the simple acclamation progression of exposing  subjects to an environment temperature of 15-16C (60F) for 10 consecutive days and then looked at the activity level of non shivering thermogenesis (NST) and BAT. (7)  At the same time they surveyed three key indicators of comfort:  How are you feeling (temperature) now? Do you think this is….(comfortable to uncomfortable)? and Are you shivering?

What is not too surprising is that after 10 days all of the questions saw a significant improvement (move towards comfort/non shivering). We’ll discuss this below. The acclimation also increased NST by 10%. Remember, this is heat generated directly through mitochondrial activity bypassing the shivering/ATP step.  While no rise in RMR was detected (I suspect they didn’t measure during cold exposure), they also don’t report RQ, so there’s no way to tell if an increase in fat oxidation was associated with the acclimation. They do state that the mitochondria became sensitive to fatty acids with the exposure. The also briefly discuss the lack of skeletal muscle recruitment seen in earlier studies by same team (above), but suggest it might be linked to intermittent exposure vs the previous continuous exposure.

Finally, It was interesting that BAT was detected in 94% of participants before and 100% afterwards – a long way from just  decade or so ago when it was believed we lost all BAT by adulthood.   Overall the detectable BAT quantities increase by 37%.  And let’s go back to the test conditions…we are talking about 60F (15C) for only 6 hours a day!  This is a great fall/spring day whether you happen to now be in the Northern/Southern hemisphere.  This is NOT cold…nor is it an ice bath or extreme.  It’s the equivalent of spending a couple of hours in cool, not cold conditions. This is something everyone could easily accomplish.

Spice it up.

Figure 1-Contribution of BAT to whole-body EE. (A and B) FDG-PET/CT images of subjects with detectable (A) and undetectable (B) activities of BAT. (C) Whole-body EE at 27°C and after 2-hour cold exposure at 19°C. (D) CIT. (E) Fat-free mass. (F–H) Relationships of fat-free mass to EE at 27°C (F), EE at 19°C (G) and CIT (H). (I) BAT activity. (J–L) Relationship of BAT activity to EE at 27°C (J), EE at 19°C (K), and CIT (L). *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 1 Contribution of BAT to whole-body EE.
(A and B) FDG-PET/CT images of subjects with detectable (A) and undetectable (B) activities of BAT. (C) Whole-body EE at 27°C and after 2-hour cold exposure at 19°C. (D) CIT. (E) Fat-free mass. (F–H) Relationships of fat-free mass to EE at 27°C (F), EE at 19°C (G) and CIT (H). (I) BAT activity. (J–L) Relationship of BAT activity to EE at 27°C (J), EE at 19°C (K), and CIT (L).

 

 

The second paper was from a team in Japan and looked at 2-hour mild cold stress (17C/62F) treatments for six weeks, 19C/66F 2-hour exposure on energy expenditure (EE), and compared these to daily ingestion of capsinoids (pepper extracts) for six weeks. (8)  Similar to the study above, a clear association of mild cold stress and increased metabolic activity was demonstrated.

In this study of 51 young men, a little over half showed BAT that was activated by the one time exposure to 19C (see Figure 1, E). Of the detected/undetected, both saw a significant increase in EE (c), but those with BAT saw 252 kcal/day vs 78.8 kcal/day. They also saw a strong association between fat-free mass and EE – in other words resting metabolic rate scaled with fat free mass.

Reflecting back on our  Part 3 of Muscling Your Metabolism,  don’t forget that lean mass scales with weight – ladies (and men), pay attention here – the more you weigh the more lean mass is under the “fat suit” to carry around those extra pounds and the higher your metabolism is to support such effort. (9) At the same time let’s also not forget that it’s also been demonstrated that the average daily energy expenditure of traditional hunter gatherers was no different than that of modern day Western (US and European) counterparts after controlling for body size; as such, “lifestyle had no effect on total energy expenditure.” (10)

So let’s look at this clearly, and accurately, in terms of my simple question above: if putting lean mass on to burn calories (clearly demonstrated in this and other studies) was our main concern, then the bigger you are the more lean mass you have and the higher the metabolic rate.

Further, if we are all just suffering from too much sedentary lifestyle and just need to go roll more boulders and chase a few antelope, then this isn’t very consistent. Your metabolism or lean mass is likely not the problem at all and that’s why one can continue to run marathons and not lose weight.   We eat too often, too calorie dense and too much.

Spread the word: you can’t out exercise your mouth. 

Now, back to the mild cold stress. What is also interesting in a cohort of similarly aged young men that fat-free mass was closely tied to EE at 27C, but not at 19C during mild cold stress (see: F-H). So this clearly distinguishes between BAT contribution to EE vs fat-free mass.  But like the study above, the 6-week, 2-hour a day exposure to 17C/60F resulted in an increase  in both BAT activity and BAT detection: individuals with no BAT detectable at the start showed active BAT at week 6 (see Figure 2A in the paper).

Obviously anyone paying attention here should see the conflict, maybe in these short term acclimation studies (intermittent) BAT becomes the first line of defense (if you have it). Further, if you don’t have BAT it seems that one can recruit it. Finally, there are also examples that even skeletal muscle can contribute in chronically cold (read natural winter exposure pre modern world).  We’ll address this in the practicum below.

Whole-body EE before and after chronic stimulation by cold and capsinoids. (A) Effects of repeated cold exposure for 6 wk. (B) Effects of daily  ingestion of capsinoids for 6 wk.

Whole-body EE before and after chronic stimulation by cold and capsinoids. (A) Effects of repeated cold exposure for 6 wk. (B) Effects of daily ingestion of capsinoids for 6 wk. ( from supplemental methods)

 

 

Finally, this study had this interesting twist of the effect of capsinoids from a specific pepper (do you hear the supplement companies beating your door down?).  This is actually an interesting class of non-pungent capsaicin from a sweet pepper (CH-19 Sweet, Capsicum anuum L.).  Reasoning that the increase in dietary induced thermogenesis was related metabolically to the heat rush stimulated by pepper exposure, they tested in a cross-over, randomized, single-blind trial comparing placebo/capsinoid capsules ingested daily for 4-6 weeks… and it worked!

Those receiving the capsiate had an increase in EE similar to the same treatment with mild cold stress.

That’s actually surprising and an interesting result.  Once again, they didn’t report the more important figure, RQ, which would tell us how much more of this EE activity is actually helping contribute disposal of stored fat.  I have first hand data that the cold exposure does decrease RQ over time (moving towards more fat metabolism).   It would be interesting to see if that played out here as well.

The Practicum – Your Autumn Experience

Ok, so we moved all over the place today and I am always asked for practical applications of all of these intellectual curiosities.  With a few extreme exceptions, the move-more message to burn fat and increase metabolism is pretty weak at best.  Further, the lean muscle burns fat argument, while true, is mostly irrelevant.  What you put in your mouth (future post) every day has far more effect on your results if fat-loss is the goal. If you want to run faster, jump higher and swim farther – exercise is the solution.  Wim is challenging the endurance portion of exercise, but that’s for another time.

This is not to say one can’t have a profound impact on metabolism with mild cold stress, but even that is not going to make up for the $1 buffet; you can’t out exercise your mouth.  The only exercise guaranteed to work is to isometrically clench one’s mouth in the presence of excess calories.  Let’s assume you’ve picked your dietary regime, be it paleo, vegan, body for life, whatever… and you want to lose.

Fall is an EXCELLENT time for the adaptation we see in all of these studies.  This is the natural period where cold ushered in and our bodies are designed to adapt – everyone can do it, don’t use the pathetic story of cold natured, big boned, or genetic destiny.  Instead, ease into it.

contrast showers help mediate cold shockI have given out one prescription for muting your immediate response to cold and increasing your cold (and paradoxically hot) tolerance.  I call it: 10-20-10x and it is a procedure Wim Hof and I developed together based on both of our experiences.  First, you need only a GYMBOSS timer (you can contribute by getting it on my Amazon store or there is a free App) and a shower (consider the silicone skin for $2).

Finish the cleaning part of shower at a normal temperature (hint, slowly reduce your shower from scalding to normal-warm over a week or so if steaming shower is your thing).  Then you’ll do 10 seconds of warm followed by 20 seconds of cold and repeat that interval 10 times (10-20-10x).  You want to end on cold for a minute or two.   It will suck pretty bad at first, don’t say you weren’t warned.  That being said, it gets not only tolerable, but the best description I’ve heard is you’ll eventually get the same “runner’s high” after a race. It really gets you going.

What is going on during this crazy exercise?  Vasoconstriction/vasodilation is alternating and blood is pulsing to and from the extremities. Believe me you will feel it in your fingers, toes and scalp.  Ladies, I am told a cold water rinse with hair closes the cuticle and my South American female followers SWEAR this tightens the buns  and skin – I don’t know, but it’s a bonus if true.  What you will find is a very perceptible increase in mood and well being – this boosts the endorphins and gives a great morning rush.  It also will slowly mute your response to sudden cold, be it opening the shower door, the office door, or cool water.  Your body eventually doesn’t panic in the “fight or flight” sense to sudden cold exposure and that helps with overall comfort.

As well, I think this is superior to just cold showers if that’s already your thing. The constrict/dilate method is additionally a great way to alleviate  post workout soreness.  Here is the modification I would make: fill the tub with cold tap water before you do this and then sit in that after the 10-20-10x for 5-10 minutes – need to submerge farther for upper body workout.  Even without ice, you will see a significant difference in following and next day in soreness – even if you are just starting to exercise.

Glove before sweater, make you look better.

So this brings me to my final couple of observations. Don’t be afraid of cool temperatures.  I am not suggesting you go out and brave dangerous cold levels (0C/32F air and 16C/60F water are the lower limits in my book), but do the reverse of common layering with skiing – bring your layers WITH you and layer as necessary; don’t wear them and remove when too hot.  Are you really going to freeze walking from the house to the car…in the garage? What about from your parking space to the warm office building? How do we dress different in summer and winter when the environments we inhabit are virtually the same?

These small times of exposure both condition you and as we have seen today have real, measurable effects on your overall metabolic pathways. Drop the thermostat a bit – it doesn’t take extreme and you will get used to it. This isn’t extreme as I have been suggesting for a few years and we don’t need super-human feats of ice endurance, not even Wim believes this as the champion of champions on the subject. What I want everyone to do if you want to get in touch with the real biological self is expose yourself to the seasons, they matter.  If you live in an extremely mild climate, then invent them.

Remember, the only species that get sick and chronically ill are us and the pets we keep warm and fed: they get the same diseases and struggle with obesity. It’s not their little doggie/kittie treadmills and the amount of “protein” in their food – it’s chronic overnutrition.  Animals conserver and so did our ancestors, despite what your rope climbing, tire-tossing, five-toed shoe friends want to believe.   I see consistently .6-.8 lbs a day loss in my clients with no exercise. Sorry again for the long delay. I am sure there will be a lot of discussion.

I don’t want to debate diet at the moment, so let’s stick to the subject and be respectful – I am thrilled that our many comments have avoided the trash-talk elsewhere. Have you been doing contrast showers for a while? Let us know your experience?

As always, I’m not selling books, supplements, or bad ideas and I self-fund my research, so if you like this PLEASE donate and perhaps consider a regular contribution. It’s appreciated and all of it goes to my mid-life crisis metabolic lab, gadgets and historical textbooks.

 

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Thanks!
Ray

References

(1) Guarente, Leonard. “Mitochondria—a nexus for aging, calorie restriction, and sirtuins?.” Cell 132.2 (2008): 171-176.

(2) Haigis, Marcia C., and Leonard P. Guarente. “Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction.” Genes & development 20.21 (2006): 2913-2921.

(3) Koubova, Jana, and Leonard Guarente. “How does calorie restriction work?.” Genes & development 17.3 (2003): 313-321.

(4) Tachibana, Masahito, et al. “Mitochondrial gene replacement in primate offspring and embryonic stem cells.” Nature 461.7262 (2009): 367-372.

(5) Fujita, Jun. “Cold shock response in mammalian cells.” J Mol Microbiol Biotechnol 1.2 (1999): 243-255.

(6) Wijers, Sander LJ, et al. “Human skeletal muscle mitochondrial uncoupling is associated with cold induced adaptive thermogenesis.” PLoS One 3.3 (2008): e1777.

(7)  van der Lans, Anouk AJJ, et al. “Cold acclimation recruits human brown fat and increases nonshivering thermogenesis.” The Journal of clinical investigation 123.8 (2013): 3395.

(8) Yoneshiro, Takeshi, et al. “Recruited brown adipose tissue as an antiobesity agent in humans.” The Journal of clinical investigation 123.8 (2013): 3404.

(9) Prentice, Andrew M., et al. “High levels of energy expenditure in obese women.” British medical journal (Clinical research ed.) 292.6526 (1986): 983.

(10)  Pontzer, Herman, et al. “Hunter-gatherer energetics and human obesity.” Plos one 7.7 (2012): e40503.

defiant healthAs I sat on my back porch early one morning in October, 2008, there was no way for me to realize how this one crazy moment would completely change my life.  Over the weekend, I attended a meeting in Philadelphia and on the last night proclaimed to a friend that I was about to do the most odd experiment in my life.  I wanted to get to the bottom of “metabolism” and “burning calories.”  I wanted to understand why it seemed so difficult to lose a couple of pounds and yet I could easily GAIN a couple in a weekend.

So on the first day of this self experiment, I was sitting in shorts with no shoes, shirt, or hat.  I wondered what was it like to be cold? I wanted to see how far I could go.  That morning it was 33F/0.5C and the following week (an unseasonable chill for the area) it ranged from 32F/0C-41F/5C. So many things about all of this were fortuitous and not planned.  My goal was simple question:

Why do I get cold and what causes me to reach the point where I must seek warmth?

For the first time in my life, I was shivering uncontrollably. I don’t think I’d ever REALLY shivered before. I started writing down symptoms and sensations. I remember at one point my already illegible scribble in my notebook becoming even more unrecognizable and I put the notebook and pen down. Closing my eyes I could feel pain in my feet and hands.  My ears, nose and face burned and shivering got a little more aggressive. At first, I could close my eyes and will my shivering away for 10-20 seconds. At some point that no longer worked. My scalp tighten and I felt all the blood struggling to stay in my limbs.

I can’t remember if it was my ears, feet, hand, or face that finally made me call it quits, but I do remember walking in on very numb feet, barely able to open the door and deciding a warm shower was in order.  Even as my hand went under the first cold water that came out of the shower head, it was burning warm.  The shower faucet was the type that had the temperature preset and there was no WAY I was taking a shower at the normally adjusted temperature – it was entirely too hot. These perceptions of change are something we are all too fast to forget; There are a range of environments we can survive and our body doesn’t sense absolutes, but is driven by change.

What I’ve learned since makes me look back and laugh a bit at how extreme I perceived that morning to be, but not because I didn’t really experience the agony. This isn’t just a melodramatic, reminiscent account – it happened as severely as I remember it. What I have learned is just how adaptable the Human body is to the world around us. As machines go we are INCREDIBLY adaptable.  Our simple, one-dimensional explanations of what we might in one moment experience or perceive are often skewed from what we are really capable of doing.

I was  just as wrong about my ideas of metabolism back then and I would argue that many physicians, nutritionists,  and fitness experts fall into the same trap.  What sets me apart now is that I am measuring metabolism weekly in range of conditions and people and it’s opened up my eyes to an entirely new world.

The Beginning

I’ve been reading/collecting/studying physiology, nutrition, and metabolism textbooks from the late 18th century to the early 19th century.  The work that was completed during this period is spectacular. What began with the Enlightenment and persisted through the Industrial Revolution was a very profound shift in how we viewed our bodies. Although there had been exploration of what we now calle metabolism going all the way back to Hippocrates (460 BC-370 BC), the progress we made during this ~125 years was simply astounding.

It’s important as one reads these classic papers and textbooks to somewhat immerse in their world.  It’s easy to see the debate of the time and it’s interesting to look back with the same clarity that  I now reflect on my first cold experiment, and know who’s right and who’s wrong.  When we look back 100 years from now, what do you think we’ll find?  We didn’t drink enough sodas or protein shakes? We didn’t take enough supplements? Where do we get our “protein” anyway? Was everyone allergic to wheat gluten?

Whether it’s the work of Becher, Lavoisier, or Atwater, there are so many hypotheses we know to be true today, but were highly debated when introduced. Yet, curiosity and perseverance caused these free-thinkers to press forward and conduct experiments and collect supporting data. They challenged status quo and it didn’t always make them popular.

For example, nearly a century past with the world’s greatest scientists all knowing that the reason things burned was due to the “phlogiston” contained within the substance.(1) These “phlogisticated” substances were “dephlogisticated” when burned. The air only had a limited amount of phlogiston it could absorb. Whether it was a candle or a Guinea pig in a sealed container, soon the air was no longer capable of absorbing any more phlogiston and the life, like the candle, was extinguished.  We now understatnd  from the work of Lavoisier that it was the oxygen in the air that diminished, but for a century, the best scientists in the world followed the phlogistic doctrine.

It interesting that nearly 200 years later, Lavoisier had it correct in his November 19, 1790 letter to Dr Joseph Black at the University of Edinburgh when he writes:

  1. La quantité d’air vital ou gaz oxigène qu’un homme en repos et à jeun consomme, ou plutôt convertit en air fixe ou acide carbonique, pendant une heure est de 1200 pouces cubiques de France environ, quand il est placé dans une température de 26 degrés.
  2. Cette quantité s’élève à 1400 pouces, dans les mêmes circonstances, si la personne est placée dans une température de 12 degrés seulement.
  3. La quantité de gaz oxigène consommée, ou convertie en acide carbonique, augmente pendant le tems de la digestion et s’élève à 1800 ou 1900 pouces.
  4. Par le mouvement et l’exercice on la porte jusqu’à 4000 pouces par heure et même davantage…”
  1. The quantity of vital air or oxygen gas that a man at rest and fasting consumes, or rather converts into fixed air or carbonic acid for an hour, is 1200 cubic French inches when it is placed in a temperature of 26 degrees.
  2. This amount increases to 1400 inches in the same circumstances, if the person is placed in a temperature of 12 degrees only.
  3. The amount of oxygen gas consumed or converted into carbonic acid increases during the time of digestion and amounts to 1800 or 1900 inches.
  4. By movement and exercise, the amount is increased up to 4000 inches per hour and even more.

Nutrition. Exercise. Thermal Load.  There it is before we even fully agreed on the existence of Oxygen. It might be interesting to note that Lavoisier did this work in his home laboratory and invited scientists from around the world to come work with his equipment.  I like that kind of career and I can completely identify with the inner passion.

This was one of a series of letters written to Dr Black in late 1790 to convince him that the phlogistic doctrine represented good observations, but was fundamentally wrong explanation at the same time.  Dr Black, a stauch advocate of the phlogistic doctrine, replied a two months later not with disdain, but with gracious respect:

…Having been accustomed, for thirty years, to believe and to teach the phlogistic doctrine , as it was understood before the development of your system, I, for a long time, experienced extreme repugnance to the new system, which represented, as absurdity, that which I had hitherto regarded as sound doctrine   Nevertheless, that repugnance, which proceeded entirely from the force of habit, hath gradually diminished, overcome by the clearness of your demonstrations, and solidity of your plan. Although there are some particular facts , the explications of which appears to be difficult; I am convinced, that yours is much better founded than the ancient doctrine…

He goes on to write,

…But if the power of habit prevents some among the older chemists from appreciating your ideas, the young students, who are not influenced by the same power, range themselves universally on your side…

This is how science is ever growing and changes, but these sorts of exchanges can now happen  happen in milliseconds in email and instead of published letters (Lavoisier’s letters to Dr. Black were not publicly published until the late 1800s).  Lavoisier, unfortunately was guillotined just three years later at the age of 50 for his participation in the Ferme générale, an outsourced tax collection service to the king [Note to self: stick with paypal donations]. It was a huge loss and we’ll never know where Lavoisier’s work could really have ended.

The Raging Fire

What strikes me about the totality of this research is the amount of time and widespread acceptance of the simple notion that man kept warm by expending caloric energy.  I’ve had more than one debate with those that should know better, but don’t seem to see the importance of this shift in our daily living environment. Of course keeping warm was an obvious part of life 200 years ago, but we’ve not learned much new to discount it’s importance in the daily balance.

Despite all that, there’s a lot more attention now and more and more people are becoming with both the idea and how it can be used.  We have discussed the  idea surrounding brown Adipose Tissue (BAT) on several blog posts, and it’s quite the rage in the media, but I want to go back to the BATgirl (Part 2) post.

In it we talked about the implications of not having any BAT at all.  We’ve also discussed the idea of exercise induced hormone, Irisin, for potentially creating new BAT, but are there other options? While it certainly can be advantageous to create or have BAT, can anyone, regardless of BAT levels, take advantage of 1) your ability to comfortably adapt to a wider range of cooler temperatures than you might otherwise expect and 2) what mechanisms might be in play when BAT’s not cause for warmth?

Remember, the way BAT causes the heat is through mitochondrial uncoupling – i.e. the cells power plant is encouraged to directly produce waste HEAT instead of ATP for cellular energy.  Since every cell has a mitochondrion for biogenesis, can mitochondrion in cells other than BAT be recruited to the causes?

There are two excellent papers I want to share.  The first is about skeletal muscle mitochondrial uncoupling from  Maastricht University, The Netherlands. (2) I will talk more about respiration calorimetry on the next post, but this study involved measuring the metabolic response in 10 lean men for both a warm (22C) and cool (16 C) environment.

 

Human Skeletal Muscle Mitochondrial Uncoupling Is Associated with Cold Induced Adaptive Thermogenesis

 

 

 

(1) James Bryan Conant, ed. The Overthrow of Phlogiston Theory: The Chemical Revolution of 1775–1789. Cambridge: Harvard University Press, (1950)

(2) Wijers SLJ, Schrauwen P, Saris WHM, van Marken Lichtenbelt WD. Human skeletal muscle mitochondrial uncoupling is associated with cold induced adaptive thermogenesis. PLoS ONE 2008;3:e1777-e1777

 

 

Irisin transforming fat to BATWe take a quick break from our macronutrient discussion to talk about some really exciting news in the hypothermics world that showed up in the last two weeks. It’s great when new data shows that old thoughts might be wrong.  This one comes from researchers at Harvard Medical School (and a host of other institutions).(1)  These scientist discovered a new hormone, irisin, named after the greek goddess iris – the personification of the rainbow and messenger of the gods.

What is most exciting is that this hormone could be another piece of the “calorie” controversy – the irritating paradox of calorie in, calorie out.  So let’s take a look at what they found.

Only the Good Die Young

In the past we have discussed the role of the uncoupling protein, UCP1, that instructs the mitochondria to generate excess heat instead of producing ATP.  This protein is mediated by another very important co-activator, PGC1-α. You may have heard about it in connection with what are called the Sirtuin proteins. If not, let’s back up and review a little on these before getting into this new discovery.

By regulating the production/activation of this family of molecules, scientist have not only been able to vastly alter obesity in mammals, they also are able to affect animal longevity.  You’ve heard of Resveratrol by now and these are the very same metabolic pathways altered by that molecule. (2-4)

PCG1-alpha altered mice show dramatically different aging.

Increased PGC-1α expression in skeletal muscle prevents age-associated weight gain and improves exercise capacity during aging. (A) Comparison of mice expressing the PGC-1α transgene in skeletal muscle (MCK-PGC-1α) and wild-type littermates (control) at different ages. (B and C) Lean and fat mass of 22-month-old wild-type and PGC-1α animals as determined by DEXA scans, (D) Relative hindlimb mass of 22-month-old wild-type and PGC-1α animals (E) Treadmill performance test at different ages for wild-type and PGC-1α animals; Source: Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20405-10. Epub 2009 Nov 16.

For example, if you look the the photo to the right, you’ll see a pair of mice. One mouse (left),  was genetically modified to have enhanced PGC1-α and compared to a normal control mouse (right).  Just a scan of the photos and you will quickly see that the modified mouse ages “gracefully.”  Its control cage-mate gets plump like the rest of us even though it’s in the same environment. The genetically modified mouse stays healthy.

It doesn’t stop there. Take a look at graph “E” to on the bottom right.  That is the difference in performance of Treadmill tests (I wonder if they used Livestrong?).  Look at the difference of performance at 22 months! Like a fine red wine, these mice get better with age.  In addition to the lack of weight gain and increased running skills, these mice showed no age-related bone loss or insulin resistance and the typical systemic inflammatory response was mitigated.

Despite what people might say, you’re not going to get these results from drinking red wine (sorry), but these are incredible first steps to unlocking the mystery of aging and metabolic syndrome.

Message to My Blubber

The new research identifying the irisin hormone is just as exciting.  This hormone was hidden as part of a much larger molecule and these researchers were able to  isolate it.  Irisin is secreted as a result of exercise in both these transgenic (modified) mice and Humans.  It turns out that this is way for the muscle to “communicate’ with the forming white adipose cells, signaling them to become the more energetic brown adipose tissue (BAT).  The concentration of this hormone jumped sharply after exercise (Human and mice).

The researchers went a step further.

By doing experiments in cultures, they discovered that nano molar levels (tiny amounts) of this hormone cause a 50-fold increase in the UPC1 protein. When delivered in vivo (in the animal) they still saw a 10-20 fold increase of in UCP1, which resulted in an increased energy expenditure and improvement in the glucose tolerance of mice fed a high fat diet.  But a nagging question remained. What purpose would be served by a hormone being released in response to exercise that INCREASED energy consumption?  One might thing that the opposite would be true – evolution would dictate conservation of energy.

Cavemen Didn’t Exercise

A long time before 5-toe shoes and grown men (and women) running through NYC Central Park beating their chest and throwing boulders, we were far more like the bird sitting on your back porch (unless you are looking at a pigeon – they don’t count); we starved.  If you look all around you and ignore domesticated animals (including pigeons and rats), you will find that every animal is starving.  They live to eat every day and it is a struggle to find calorie.  It is THE struggle that anthropologist are still trying to unravel with Humans.

Where did we get the energy to become the modern-day intellectual giant?

You should see the conflict. If we were starving and now find that a hormone is released in response to strenuous activity, which turns energy storing white fat into energy burning brown fat, that would be a NEGATIVE not a positive evolutionary trait. The quest to find food would be a downward energy spiral.

Ah, but we really had no reason to run through the park or roll giant tires around. Why would our ancestors need to exercise?  It turns out that there is one activity that WOULD cause a lot of muscle activity, yes it’s shivering.  It was a way for animals to keep warm and in response to the biological stress of cold, muscle secreting a hormone to create more BAT to keep warm was a GOOD thing.  It meant staving off hypothermia.

A further interesting fact is that PGC1-α was originally discovered by scientists, because it was unregulated by cold exposure.  We also know that in addition to caloric restriction, mild cold stress is the only other way that we have demonstrated longevity in mice. Even more exciting is that recent tests (unpublished) have show a nearly 5-fold increase of BAT output of a 52 year old man vs 20 year old controls.  This increase was even though they had similar levels of BAT, so there is even more energy to tap into. You can adapt and cause increased metabolic activity.

Un-wrapping it All

I think we are seeing just the tip of where all of this is going. In the last decade we have moved from the idea that we lose all of our BAT with aging, to we have a fixed amount of BAT, to now understanding there are hormonal mechanisms to create new BAT.  Further the exact pathways that are responsible for longevity through caloric restriction also are affected by mild cold stress.  These systems respond to biological stress of starvation and cold, like a muscle responds to the stress of weight training,  by creating a more resilient biology.

Mild cold stress does not have to be miserable, or even cold.  It can come in a lot of different forms. In the David Agus new Book, The End of Illness, he discusses at great length the role of inflammation in aging. He even gives an example of a one of his “all-star” cancer patients. Diagnosed with prostate cancer at the age of nearly 80, he decided to make a life changes that include swimming every day. He is now almost 90 and doing incredible.

I have documented the profound ability to thermal load through swimming.  In addition we know that mild cold stress starts in warm water (27C/80F).  Today we have learned that a hormone has been identified that is not only increases PGC1-α, it’s causes all the benefits of longevity seen through sirtuin activation. It’s exciting to see this all come together and I know we’ll only learn more. This is not the ice cube diet or really even “freeze your ass off,” it’s a basic adaptation with millions of years of evolutionary excellence.

Turn the heater off, go for a walk, let go of a few layers, move,  or just swim – do something.  You have nothing to lose and we all look funny as hell in shorts, gloves and face masks.  If laughter is the best medicine, worse case is you’ll make someone live longer by laughing.

Ray

 

(1) Boström PA, et al.,  “PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis,” Nature. 2012 Jan 11. doi: 10.1038/nature10777. [Epub ahead of print]

(2) Wenz T, et al. “Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging,”Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20405-10. Epub 2009 Nov 16.

(3) Tong Shi, et al. “SIRT3, a Mitochondrial Sirtuin Deacetylase, Regulates Mitochondrial Function and Thermogenesis in Brown Adipocytes,” J. Biol. Chem., Vol. 280, No. 14, Issue of April 8, pp. 13560–13567, 2005

(4) Marcia C. Haigis and Leonard P. Guarente, “Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction,” Genes Dev. 2006 20: 2913-2921.

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Ray

BAT, Brown Adipose Tissue, Thermal diet and weight lossWe learned in Part 1 that not only do human infants start out with more fat than any other species, a higher percentage is brown adipose tissue (BAT). Women, in general have more than men and as Humans age, BAT seems to dwindle. It’s likely if you have ever been obese, you have less BAT then your skinny friends.Custom gummibåt

I have dozens of papers here on BAT. My interest with BAT began after Tim and I discussed it at length and started exchanging ideas and data. Honestly, I came to my conclusions from the complete opposite (but complimentary) approach – it was much more of a 30,000 ft level view on the subject. Read Full Article →

It’s been an incredible 6 weeks… I really appreciate all the emails and comments and the amazing number of people that have signed up to read and follow this site.  I know what everyone is asking,

“Ray, can you just tell me what to do?”

The answer is YES, but hang on a bit. One thing I expected would happen is the  “me too” people  that would just start driveling about being cold and losing weight. The other expectation was that it would be presented as miserable and extreme. I wanted to support the ideas within The 4-hour body before beginning to suggest alternative/complementary approaches. Unfortunately, the health and fitness industry is loaded people that earn expert status by learning a few new words. Face it, we’ve never been more unfit as a species and we’ve also never spent more achieving it. That’s quite a contradiction.

Perhaps it’s time to change that even if it’s just a small group of us.

Read Full Article →