Is a Calorie a Calorie? New study says, “No.”


A new study published in JAMA refutes the commonly held assumption that all calories are equal in terms of how they effect our metabolism (at least in a small group, n=21, of semi-starved obese subjects each rotating through different weight-maintenance diets for a month).  When subjects consumed an Atkin’s-like diet (Table 1: 10:60:30 % carb/fat/protein), they burned, on average, far more calories a day then when they were on a low-fat (60:20:20 % carb/fat/protein) and low glycemic index  diet (40:40:20 % carb/fat/protein) (Table 3: ~325 and ~200 calories a day more, on average, respectively) while on the SAME AMOUNT OF CALORIES with subjects exercising LESS on low carb diet than other two diets (also, the higher thermic effect of burning protein, 10% higher in Atkin’s, should have been offset by the higher carb% in the other two diets so this cannot explain the different metabolic rates).

This means when subjects were on the low-fat diet, they would have to exercise moderately for around an hour a day to meet their metabolic rate while on the Atkin’s diet: lead author, Dr. David Ludwig, explains in an MSNBC interview, “”That’s an amount equal to one hour of moderate physical activity, without lifting a finger.”  Researchers did not measure the weight or % body fat change by diets, possibly because four weeks was too short a time to see a change.  However, the increased metabolic rate on Atkin’s might lead to lower weight over-time compared with the less metabolically-active low-fat and low-glycemic index diets.  Lustig explains this metabolic difference according to the “insulin hypothesis of obesity” that the higher carbohydrate intake of the low-fat/GI diets raised insulin relative to Atkin’s which essentially lowered subjects’ metabolic rate, a common effect of starvation, as lead author, Ludwig remarked).  Lustig explains insulin, starvation mode, and why diets fail here.

Also, cholesterol measurements were better on Atkin’s then the other groups (i.e. HDL was higher and triglycerides were lower-meaning the group that ate the most fat had the least fat in their blood, a paradoxical but commonly observed effect of a very low carb, high fat diet relative to low-fat, high carb diet).  Subjects were also less insulin resistant on Atkin’s then the other diets (strangely, insulin resistance might be the primary underlying cause of metabolic syndrome, a precursor condition that might lead to many of the chronic diseases afflicting Westernized-countries like  hypertension>stroke, dyslipidemia>heart disease, hyperglycemia/hyperinsulemia>diabetes, cancer, Alzheimer’s, etc.).  Higher insulin sensitivity results in Atkin’s were measured as higher peripheral and hepatic insulin sensitivity levels which indicate, obviously, higher insulin sensitivity and less insulin resistance.  Leptin levels were also lower with Atkin’s, meaning risk of “leptin resistance,” a possible key factor in obesity and insulin resistance, might be lower with lower carb intake.  The only possible downside to Atkin’s was a slight elevation in stress (measured by cortisol) and inflammation (measured by c-reactive protein, or CRP) but these levels were both significantly lower than before the weight loss and well within healthy, “normal” ranges, at least according to (CRP, cortisol).  However, it is possible that subjects had not fully adapted to ketosis (burning fat and protein metabolites for fuel as opposed to glucose) and that this elevation was simply a temporary marker of this metabolic transition (this is simply a guess on my part, I could be wrong).

The lead author, Dr. David Ludwig, summarizes the results:

“The low-fat diet produced changes in energy expenditure and serum leptin42 – 44 that would predict weight regain. In addition, this conventionally recommended diet had unfavorable effects on most of the metabolic syndrome components studied herein. In contrast, the very low-carbohydrate diet had the most beneficial effects on energy expenditure and several metabolic syndrome components, but this restrictive regimen may increase cortisol excretion and CRP.”

My take:

These 21 obese subjects might be fundamentally different then other obese adults (now around 36% of the U.S. adult population), meaning that these results are not “representative” of most obese U.S. adults and therefore unimportant.  This may or may not be ture.

Regardless of whether these subjects represent most obese American adults who have dieted or not, in my opinion, this study is still hugely important because it likely provides a small glimpse into why dieting, in the conventional low-fat, high carb sense, is so hard, why so many adults yo-yo diet, and why most obese people regain lost weight (or even surpass their pre-diet weight).  This study might, if replicated in larger, longer future studies, explain why we have an obesity epidemic.

The simple explanation for what this study found is that eating calorically-identical diets of different nutrient composition (measured by carbs, proteins, and fats) led to different metabolic rates and different metbolic disease risks for the subjects.  Therefore, equal caloric intake of different nutrients might lead to different risks not only for cholesterol, inflammation, and insulin resistance, as most people accept as obvious, but for weight gain and, therefore, obesity as well.  It is this latter finding that is so radical and potentially useful, if these results are replicated in larger, longer studies (which is what is required in science for us to actually explain causality).

Therefore, the results suggest that if you are obese and want to lose weight and, more importantly, maintain weight loss, reduce the amount of sugar and refined carbohydrates you eat (possibly including whole grains) and replace them with fat and natural carbs (unlimited green veggies and moderate-GI fruit like berries and the occasional apple).  Eating processed foods like refined carbs (grains, starches, and sugar) elevate your blood sugar and insulin and damage your liver (fructose especially), which reduces your metabolic rate and increases your risk of metabolic syndrome.  Stop eating them, eat whole foods, and stop fearing fat, esp. saturated fats (because you have to replace the carbs with something and humans likely evolved to eat saturated fats so, if an animal’s ideal diet is eating what an animal evolved to eat, how could they be harmful?).

Lastly, everyone is different so even though the averages were better on low-carb for obesity and metabolic syndrome risk, a small number of people did better on a low-GI diet than low carb (see Fig. 3).  This means that while most obese people may be obese due to “carbohydrate intolerance” and would do better on an Atkin’s-like (or Paleo-style) diet than low-fat or low-GI, low-GI might be better for some.


Researchers semi-starved (“calorie-restricted”) 21 obese adults until they lost ~10-15% of their body weight.  Subjects were then assigned to eat three isocaloric (same # of calories) diets each with a different % composition of carbohydrates, fats, and proteins in random order (a cross-over design) for a month each and their metabolism, cholesterol, and other markers of insulin resistance (peripheral and hepatic insulin sensitivity) and inflammation (cortisol, csRP) were measured and compared with pre-weight loss and compared to each other (i.e. subject’s metabolic rate and cholesterol on low-fat was compared with the same subject’s met. rate and cholesterol on low-carb, etc.).  The diets were: low-fat diet (60% carb, 20% fat, 20% protein), low-glycemic index (40% carb, 40% fat, 20% protein), and very low-carb diet (10% carb, 60% fat, 30% protein).

Commentary on this clinical trial:  for more information from smarter, more-informed people than me, read these:

An insulin-hypothesis skeptic: Dr. Stephan Guyenet 

Insulin-hypothesis believers: Gary Taubes and Dr. Peter Attia.

Somebody in the middle: Dr. Robert Lustig


How Stem Cells may be the Primary Culprit in Heart Disease

Here is an interesting link to an NPR “Science Friday” discussion with a Stanford researcher that points to adult stem cells as the primary cause of plaque generation leading to heart disease.

This still leaves the debate open on what the primary culprit of the vascular injury process actually is.  What is injuring the cell lining that leads to stem cell accumulation and the subsequent plaque (i.e. “scar tissue”) formation?  It may be that damage to the endothelial cells of the vessels is caused by small-dense LDL particles (apo-B particles – which are likely elevated on a high sugar, refined carb diet) that are oxidized and then start the foam cell process.  This inflammatory damage then may spark the stem cells to activate and form a plaque (~scar tissue).  I’m no expert though…

Why the French don’t get heart disease despite eating a ton of butter and animal products

Why does the “French Paradox” exist?  Why can the French eat huge amounts of butter, full-fat dairy, and organ meat (all of which contain huge amounts of saturated fat) and yet not have high levels of heart disease in their population?

Besides the fact that saturated fat likely does not cause heart disease (at least, without reaching a simultaneous threshold in carb intake), a protective factor may exist in all of this fatty, animal goodness: Vitamin K2 (specifically, the MK-4, or menatetrenone variety).

It may be that Vitamin K2, found in copious amounts in certain types of butter, eggs, dairy, and meat (including organ meat like foie gras), works with Vitamins A and D to remove calcium from the bloodstream and therefore prevent calcium buildup in arterial plaques (which can lead to heart disease).  This may be why the French have (or had) such low rates of heart disease despite eating huge amounts of saturated fats from animal products.

According to this hypothesis, more Vitamin K2, in conjunction with Vitamins D and A, means less calcium in the blood, and less heart disease.

Dr. Stephan Guyenet, a PhD in Neurobiology, describes this potential link on his blog, Whole Health Source.  He’s crazy smart and crazy prolific so check out his site.














Please send me any comments you may have.

The Paleo Lifestyle Explained by a Harvard PhD Organic Chemist

Here is a 2010 interview with Harvard chemist, Mat Lalonde.  He’s a really smart dude and very articulate and scientifically accurate in his explanation of the current state of scientific research as it relates to human nutrition.

All credit for the interview goes to Daniela Andrews of The National Post newspaper.

Why Diets Fail: or, Why so Many Yo-yo Diet, Why Mother Nature is Unfair, and Why It’s Not Your Fault


Diets almost always fail because they make you hungry, depressed, and prime your body to regain body fat at a lower caloric level than your pre-diet basal metabolic needs required once normal eating resumes (even with only moderate caloric restriction).  Hence, most people on these diets “yo-yo” between a lower weight and an ever-higher body weight because eating less than the body requires (“semi-starvation”) triggers an abnormal hormonal environment (study) that leads to the inevitable regain of lost fat mass when any form of “normal” eating is resumed (see Lustig video here).   Researchers refer to this as “poststarvation body fat overshooting” and was experienced by, to name one well known, very-strong willed individual, Christian Bale in his efforts to regain weight between “The Machinist” and “Batman Begins” (the reason I say “strong-willed” will become apparent later).

Therefore, if a 6 foot 200 pound man who just dropped 50 pounds eats the same amount of food as a visibly similar 6 foot 200 lb. man who never dieted, the former dieter will get obese again while the lean man will stay lean.  Mother Nature is cruel.  And for the very, very small minority of obese people who successfully lose weight and keep it off, they must starve themselves, literally forever, if they are to remain at their lower weight.  Almost no one can do this.

This means that diets might actually be counter-productive when it comes to body fat loss  and lead to greater weight gain over time .  Yikes.

Unabridged Post:

Whether you’re carrying a few extra pounds, have a “muffin top,” or are so fat that your corpse causes a crematorium to overheat, when you talk to your physician, read a magazine, watch the news, or talk to your cousin who just got their dietitian’s license, you’ll hear the same mantra: you are fat because you eat too much and move too little.  This statement is considered sacrosanct by the top health authorities around the US and the globe (including, but not limited to: the WHO, NIH, CDC, The US Surgeon General, AHA, “Biggest Loser” trainer, Jillian Michaels[ii],[iii],[v],[vi],[vii],[viii]    

They’ll then tell you to “eat less and move more” — as if you hadn’t thought of this.  Do they honestly believe that you, after years and possibly decades of trying to reduce your adiposity, hadn’t actually heard this advice and tried it?!   After all, who wants to be fat in a society that equates obesity with a lack of willpower, maturity, intelligence, class…?  The fact that you, the fat person, know what to do yet cannot do it, means that lean people judge you as “triply” weak and lazy: 1) you got fat so are weak and lazy 2) you know how to get thin yet cannot so are doubly weak and lazy 3) even if you lose weight, you were once fat so are weaker and lazier than a person of similar weight who was never obese.  In reference to #3, obese people who lose weight are even judged, at least in one study, to be less-attractive than people of the same weight/height who never were obese.  This anti-obesity stigma may depend upon which culture we’re looking at as anti-obese stigmas may be stronger in white populations than black populations, at lease in regards to female obesity (obesity).

So you try to lose weight again.  You then go off and buy some running shoes, join a gym, start a bootcamp session, and start counting calories and eating carrots and cottage cheese for breakfast and skinless chicken breast with spinach for dinner for 3 months.

You lose 20-30 pounds. Your clothes fit better.  You’re proud of your accomplishments and people applaud your efforts (usually in a condescending fashion, as if you’re a kid who learned toilet training – and the amount of condescension is probably directly related to how fat you were prior to your efforts).

However, the fact remains that, despite your weight loss, you’re hungry all the time, likely lethargic, , and your libido might dip (if you’re a male, quite literally – pun intended).

You reach your goal weight and consciously or unconsciously decide to reward yourself (and quell the ever-present hunger) by eating like your lean counterparts.  Before you know it, you’ve gained all the weight back.

But HOW!?

Caloric-restriction, i.e. eating less than your body requires for daily metabolic needs, drives the body to enter “starvation mode,” a lovely state of hormonal disorder that includes lowered metabolic rate, hunger, lethargy, depression, low libido, and an ever-present obsession with food.  Secondly, entering this state means that the fat tissue is likely re-regulated to regain its fat stores at a lower caloric level (whether this regulation occurs at the level of the brain’s hypothalmus or the fat tissue itself, is debated).

The sad state of affairs is that the advice to “eat-less and move more” has been ubiqutous for decades (see USDA Dietary Guidelines from 19802010) and yet obviously does not work as we’re still in the midst of an ever-worsening obesity epidemic that is affecting all ages and genders in our nation.

If eating less and moving more does not generate long-term weight loss (and, of more importance, metabolic health, which is the main point of obesity prevention and treatment), then it needs to be abandoned in favor of a better, more effective hypothesis.

What might this hypothesis be?  I’m not sure.  Perhaps it’s all about reducing circulating insulin levels to access our stored fat for fuel (see Peter Attia video).?  Maybe it’s about reducing the palatability of foods to reduce over-consumption(see Stephen Guyenet)?

I think the first step would be to reduce sugary drink consumption through high taxation, restriction on sales in schools, hospitals, etc., and massive education campaigns (see Lustig article and video).

What do you think?  Feel free to comment below or send me  a message.


[ii] WHO. (2011). “Media centre: Obesity and overweight.” Retrieved from:

[iii] The Centers for Disease Control and Prevention (2011). Overweight and Obesity: Defining Overweight and Obesity. Retrieved from:

[iv] American Heart Association. (May 5, 2011). “Obesity Information.” Retrieved from:

[vi] NIH, NHBLI. (Nov. 1, 2010). “What Causes Overweight and Obesity?” Retrieved from:

[vii] US Dept of HHS, US Public Health Service. (2010). “The Surgeon General’s Vision for a Healthy and Fit Nation.” Retrieved from:

[viii] National Heart Lung and Blood Institute, National Institutes of Health. (2012). “Balance Food and Activity: What is Energy Balance?” Retrieved from:

Shadowing a Diabetes Doctor, or, You are what your hormones decide you are – May 24, 2012

I had the opportunity to shadow a veteran endocrinologist for 4.5 hours Thursday morning.  It was a fascinating experience to see the treatment of actual diabetic patients instead of staring at diabetes data trends on a CRT computer screen.

The physician, who has been an endocrinologist for nearly 30 years, estimated that his practice consisted of 60:40 diabetes / thyroid patients.

Most diabetic patients we saw were older (>50) and had excess belly fat (possibly an indication of metabolic syndrome, i.e. insulin resistance).  And the greater the age and body fat, the greater the complications of their diabetes (which makes me quake with fear at the future health of children and adolescents with type II diabetes).  Most appeared to have circulation issues that led to swelling in the feet, discoloration, and/or dry skin around the ankles.  Circulation issues can disturb immune function which can lead to amputation: this latter problem was very scarily portrayed in HBO’s “Weight of the Nation” in which an older man required a leg amputation due to his uncontrolled diabetes.  The physician informed me that uncontrolled diabetes is the leading cause of amputation in the nation.  One very obese patient had venous insufficiency (which I assume is related to long-term, possibly poorly controlled diabetes but I cannot be certain).

Ultimately, the complications resulting from long-term diabetes are vast and severe and one causative factor appears to be the long-term accumulation of AGEs in the vascular system (advanced glycated end products, i.e. proteins and other molecules with bound glucose, due to chronically abnormally elevated blood glucose and high fructose consumption).  These glycated molecules bind together and clog/disrupt blood flow and, for capilaries, can cause hemorrhaging (which can lead to blindness in severe diabetic retinopathy, now the leading cause of blindness in working age Americans).

The accumulated damage to the vascular system can impede blood flow, oxygen distribution, and lead to nerve damage (diabetic neuropathy), which is why many diabetic patients we saw Thursday had their feet tested for nerve sensation with what is basically a 10 gauge fishing line.

All in all, diabetes is a frightening disease and prevalence, especially of type II diabetes, is reaching tremendous levels (~25 million adults, ~8.3% of population, with another 79 million people estimated to have prediabetes).  The US population prevalence has increased hugely over the past 50 years in conjunction with increases in obesity (most diabetes being type II, likely due to the effects of insulin resistance).

We also saw a handful of patients with thyroid issues, including 3 women with low thyroid levels related to thyroid surgery and 2 men for low testosterone levels.  Both of these conditions appeared to cause weight gain which supports the hypothesis that obesity may be a hormonal disorder.

One women complained of being unable to lose weight after significant dieting for three months despite subsisting primarily on yogurt, carrots, and eggs and minimizing calories.  Another man stopped his testosterone therapy and reported substantial weight regain (similar to Vince Vaughn and cigarettes, suggesting that hormones are driving weight loss/gain in various ways).  I am unsure how thyroid hormones affect weight other than affecting metabolic rate (which might simply be a downstream effect of hormonal action) but sex hormones are known to reduce fat levels by acting on enzymes on the fat tissue (estrogen and testosterone downregulate LPL enzymes on fat tissue which should limit triglyceride stores in fat cells).  Testosterone pellets are now gaining greater acceptance as positive results emerge and FDA approval has occurred.  One patient was offered this therapy and said he preferred it as the testosterone gel was ineffective and risky around children as the hormone can be transferred between patient and child and absorbed through the skin.

All in all, the day was a fascinating glimpse of the massive effect that hormones have upon the human body and mind.  Most individuals would claim that they have control over the state of their health.   They can control their weight, their mood, their energy levels, etc. etc. by simply acting from free will.  However, the fact that hormones have such a strong hold over the biological processes of our body severely weakens this belief.  If your hormones drive you to fatten, become hyperactive, stay awake, etc., then that is what you will do.

Therefore, because human health and even  behavior are driven by hormones than the understanding and control of our hormonal system, through the field of endocrinology, is all the more important.