July 3, 2012

Philosophiae naturalis

Good science, bad interpretation

by Peter Attia

Read Time 9 minutes

In 2012, the Journal of the American Medical Association (JAMA) published a study entitled Effects of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance. While I’m guessing most readers have not read this study, I’m pretty sure most of you have heard about the results as it was all over the news this week.

I was fortunate enough to read an embargoed copy two weeks prior to publication with the caveat that I could not speak about it until it was released publicly. Furthermore, I’m friends with one of the reviewers who told me months prior that “a very interesting paper was going to hit a highimpact factor journal very soon.”  Completing my disclosure, I had become acquainted with the senior investigator on this study, Dr. David Ludwig at Harvard.

This study sought to test an important question:

When an overweight or obese person loses weight, how does their choice of macronutrients impact their tendency to regain lost weight?

This is important, of course, because as most of us know that while losing weight is difficult, keeping it off is even more difficult.  In fact, as the authors point out, only about 15% of people who lose 10% of their bodyweight can maintain the weight loss for up to one year.  The obvious question is why?

You’ll recall from this post, that we must always obey the First Law of Thermodynamics.  In other words, we accumulate stored energy (e.g., fat mass) when we are in a positive energy balance and we lose stored energy when we are in a negative energy balance.

Energy balance is a function of two variables:

  1. Energy input – what we eat
  2. Energy output – what we expend

Furthermore, energy output can be broken down into four sub-components:

  1. Resting energy expenditure (REE) – the amount of energy expended to stay alive at rest (e.g., energy required for basic cellular function like ion transport and respiration)
  2. Thermic effect of food (TEF) – the amount of energy required to process and digest food (I also include in this category the amount of energy lost as undigested material in stool)
  3. Activity energy expenditure (AEE) – the amount of energy expended by exercise and non-exercise movement (I consider these as two forms of expenditure)

The sum of REE, TEF, and AEE is called, appropriately, total energy expenditure (TEE).

Of these, REE is the dominant “sink” of energy output in most people, and it is generally proportional to bodyweight.  I’ll cover the importance of this momentarily.

The traditional model of obesity, the so called “calories-in-calories-out” model, says that obesity is caused by the energy input terms exceeding the energy output terms.  In the words of one prominent obesity researcher, “While it is mathematically true that someone who has gained weight has consumed more energy than they have expended, using the First Law to explain why someone gains weight is of little help.  The First Law is descriptive but not explanative.”

I couldn’t have said that better myself.  The mistake most folks make when using the First Law to explain weight gain (versus using the First Law to describe weight gain) is that they lose sight of the fact that these variables – input, REE, TEF, AEE – are linked.  They are dependent on each other.  They don’t exist in isolation.

Proponents of the Alternative Hypothesis argue that intake (i.e., food) plays a role on hormones and enzymes in the body that have a resulting impact on energy output, and even subsequent input.  For example, eating one food over another can increase or decrease appetite, increase or decrease REE, increase or decrease AEE, and even impact TEF.  While the effect on each of these may be modest in isolation, even small changes over the course of days can result in significant changes over months or years.

What does all of this have to do with this study?

The figure below shows how the study was conducted.  This was a prospective design 3-way crossover study of 21 overweight or obese subjects with an average BMI of 34.4.  Each subject underwent a 20-week run-in phase, which is very common in weight-reduced studies.  During the run-in phase all baseline measurements are collected, including body composition by DEXA, TEE by doubly-labeled water, substrate utilization by respiratory quotient, and plasma levels of various blood markers (e.g., lipids, blood chemistry, hormone levels).  No, unfortunately, lipoprotein particles were not counted.

During the 12 week weight loss phase caloric intake was reduced until each subject lost 12.5% of their starting (stable) weight.  For the final 4 weeks of the run-in phase energy intake was again calibrated to hold their now-reduced-weight stable.


The figure below summarizes the data from Table 1 of the paper, showing the breakdown of macronutrients during the run-in phase and the subsequent 3 dietary interventions, each lasting 4 weeks.  Again, each subject did each diet for 4 weeks due to the 3-way cross-over design.  In other words, each subject spent a total of 32 weeks in the study (20 weeks of run-in and 3 x 4 weeks of each intervention diet).


How did the diets impact energy expenditure?

The figure below shows the change in REE and TEE measured for all groups.  There was no difference in total physical activity or exercise, so presumably there was no appreciable change in AEE.  I could not find a mention of TEF, suggesting it was not measured.   These figures are a bit ugly, but they convey helpful information.  Each dot represents an individual subject and the lines joining each dot allow you to see the change for each subject across the 3 diets.  The blue box shows the mean change (middle of the box) with the 95% confidence interval above and below.  The height of the box is therefore two standard deviations.



A few things stand out from these results:

  1. The group consuming a very low carbohydrate diet had a higher REE and TEE than the low GI group, which had a higher REE and TEE than the low fat group. In other words, the fewer carbohydrates in the diet, the higher the resting and overall expenditure.  This is actually the sine qua non of the alternative hypothesis: something beyond the actual number of calories is playing a role in how the body expends energy.
  2. As expected, given that each subject was starting from a weight-reduced state, the REE was lower for each group, relative to their baseline.  REE is highly (though clearly not entirely) dependent on body mass.
  3. There is enormous variation between subjects by diet type.  For example, at least one subject saw a dramatic increase in TEE on the low GI diet versus the other two, while another saw the greatest TEE on the low fat diet.  This speaks to a theme I iterate on this blog: be willing to self-experiment until you find what works for you. 

How did the diets impact metabolic parameters?

The table below shows the changes in hormone levels and metabolic syndrome biomarkers.

One thing that really jumped out at me was that it is quite likely that not one of the subjects in the study met the formal criteria for metabolic syndrome.  MS requires at least 3 of the 5 parameters (blood pressure, waist girth, fasting glucose, HDL-C, and TG) exceed threshold.  The thresholds are as follows:

  1. BP > 140/90 [No subject met this at baseline]
  2. Waist girth > 40 inches (men), >35 inches [Not reported, but let’s assume at least some subjects met this]
  3. Fasting glucose > 100 mg/dL [Not reported, but let’s assume at least some subjects met this]
  4. Fasting TG > 150 mg/dL [No subject met this at baseline]
  5. HDL-C < 40 mg/dL (men), < 50 mg/dL [No male subject met this, but it’s possible some female subjects did]

This may speak to the age of the subjects, which averaged 30.3 years, but I would have expected a worse set of baseline metabolic parameters. It also speaks to the point that just because someone is obese doesn’t mean they have metabolic syndrome and vice versa.


Tables are a bit cumbersome, so I took the liberty of graphing some of these results, mostly because I just can’t resist playing with think-cell (PowerPoint without think-cell is simply a tool for torturing people.)

I’ve explained p-values before, but let me explain the two types of p-values reported above and below.

P_overall is the p-value testing the hypothesis that the mean outcome of the three diets was equal.  The smaller this value, the more likely the differences were not due to chance.  As a general rule, if the p-value is greater than 0.05 we say the difference is “not significant.”  Most use a more stringent requirement of 0.01 to hit the mark of statistical significance.

P_trend is the p-value testing the hypothesis that the mean outcome of the three diets showed a trend from low fat to low GI to low carbohydrate.


Not surprisingly, the low fat group experienced a significant reduction in HDL-C.  It’s been documented many times that dietary fat raises HDL-C and dietary carbohydrates reduce HDL-C.

Each group also experienced a reduction in triglyceride (TG) level.  Since we know carbohydrates, not fat, raise TG, you may wonder why this was even the case in the low fat group, which actually increased carbohydrate intake.  I suspect it was a carbohydrate “quality” issue.  I’m guessing the baseline levels reflect more sugar consumption than the low fat phase.  Nevertheless, and again not surprisingly, the high fat-low carbohydrate group experienced the greatest improvement in plasma TG levels.



Insulin sensitivity was measured according to a protocol in this paper.  The protocol uses time blood draws after an oral glucose challenge.  The higher the index, the greater is the insulin sensitivity.  Each diet improved both hepatic and peripheral insulin sensitivity and both the overall differences and the trends were significant.

If insulin is the most important hormone regulating fat metabolism and accumulation, leptin is certainly a close cousin.  Leptin is a hormone secreted by fat cells that plays an important role in regulating appetite and some metabolic functions.  High levels of circulating leptin can be suggestive of leptin resistance which, like insulin resistance, tends to be a marker for metabolic derangement.  I’ll write a lot about leptin in subsequent posts.   While leptin sensitivity was not directly measured as insulin sensitivity was, the significant reduction in circulating leptin levels suggested it was also improved in all groups, though greatest in the low carbohydrate group.

How did the diets impact inflammation?

Two markers for inflammation were evaluated in this study, C-reactive protein (CRP) and plasminogen activator inhibitor-1 (PAI-1).  Neither is particularly sensitive in the way, say, Lp-PLA2 is (this was discussed in the cholesterol series). Nevertheless, they give us some indication of how much overall inflammation exists in the body.


Each group experienced a significant decline in both PAI-1 and CRP, and there was no significant difference between the groups for either marker.  However, the trend was (barely) significant favoring the low carbohydrate group for PAI-1 and favoring the low GI group for CRP.  Sorry low fat, you didn’t win either.

I know what you’re thinking because it was the first thought that ran through my mind when I saw this table:  What?  Is this meaningful or is it an example of statistical chicanery?  I’ll let you decide, but I’m pretty sure I know the answer.

Because I know some of you will ask, I will comment in a subsequent post on the changes seen in TSH, T3, and cortisol.  These topics deserve a post of their own.

What should have been taken away from this study?

This study reproduced a number of results which have been noted for decades:

  1. Low carbohydrate, high fat diets reduce TG and raise HDL-C more than other diets.
  2. Low carbohydrate, high fat diets improve insulin sensitivity more than other diets.

It never hurts to hammer those findings home again, but the really dramatic finding of the study was the impact of macronutrient balance on REE and TEE.   At previous count (circa 2011), 81 studies over the past 80 years involving 4,094 subjects for more than 1.2 million subject-days have attempted to ask this question – many of them attempting to “prove” that all calories are created equally.  While none (i.e., not one) have refuted the alternative hypothesis, most of them had enough methodologic limitations that it was difficult to know for certain if the type of food – rather than the number of calories – was playing an important role.

This study, while still limited (e.g., short duration, small sample size), makes one of the more compelling cases that all calories are not created equally.

What was taken away from this study?

The embargo on this paper was lifted at 4:00 pm EDT on Tuesday, June 26, 2012.  Within about 30 minutes I was being bombarded with news stories that, if you hadn’t read the study, as virtually no one actually does, would suggest that the low carbohydrate diet was the “worst” of the three diets tested.  This was not universally true, in fairness to the media, but there was no shortage of this sort of commentary:

USA Today

…the authors note a downside to the low-carb diet: it appears to raise some risk factors for heart disease.

Marion Nestle, a nutrition professor at New York University, says longer studies conducted among people in their own environments, not with such controlled meals, have shown “little difference in weight loss and maintenance between one kind of diet and another.”

George Bray, an obesity researcher at Pennington Biomedical Research Center in Baton Rouge who has also studied this topic and who wrote the accompanying editorial in JAMA, says that other studies “show that you can do well on any diet as long as you stick to it. Adherence is the major key for weight loss and maintenance. There is no magic in any diet.”

The New York Times

…the low-carb diet “also had marked problems. It raised levels of CRP (c-reactive protein), which is a measure of chronic inflammation, and cortisol, a hormone that mediates stress.”

The Wall Street Journal

…the low-carb diet had the biggest boost in total energy expenditure, burning about 300 calories more per day than those on the low-fat diet — about the same as an hour of moderate exercise. But that bump came at a cost: increases in cortisol, a stress hormone, and a measure of inflammation called CRP, which can raise the risk of developing heart disease and diabetes.

Some of these comments were patently false (e.g., “the low carbohydrate diet raised levels of CRP” according to the New York Times), reflecting utter incompetence, but most of them commit a different journalistic sin: They miss the forest while machinating on one leaf.

Tragically, most people (unfortunately this includes physicians, dietitians, and politicians) have neither the time nor scientific discipline to wade through these studies and understand their implications.  Instead, they rely on “reputable” journalists to translate for them.

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  • Esther

    Thank you so much for this!
    I had heard about this one through a source that stressed the inflammation and declared the low GI diet the winner.
    It is good to have an overview that gives the actual findings in a readable format.

    • Make sure you share it with your source, please.

  • RokShox

    “Energy balance is a function of two variables:
    1.Energy input – what we eat
    2.Energy output – what we expend”

    3. What we store as fat.

    What is so hard to understand about the energy partitioning argument? It’s infuriating. If your body is fat-building, it will rob calories to make fat at the expense of available energy. How many times does this have to be explained to you?

    • Sorry to be infuriating to you, but I think I should be infuriated by *you*. If you’d actually look at the post I wrote on this, you’d note that E_s (the change in stored energy – i.e., fat mass) = E_in – E_out. All you’ve done (I think) is rearrange the equation to state 0 = E_s – E_in + E_out.
      Congratulations on using first grade algebra to rearrange a simple equation. Excellent value add. And I like that you were able to do this while being repeatedly and consistently rude. Do you think being insulting impresses me?

    • greensleeves

      “3. What we store as fat.”

      What is interesting is that when a certain very prominent nutritionist from New York was here in SF recently talking about her new book on why calories count, she explicitly denied any role for uncoupling, partitioning, or insulin. As best as I could make out her opinion, it appeared she would deny that chemical reactions in breaking down protein or building fat lose energy for the body. No energy can be lost or gained, she seemed to say, so any claims that uncoupling “loses” energy available to the body is false and bad biochemistry. Everything you eat is burned or stored as fat. Nothing is diverted into heat or other chemical reactions. I was a little astonished at this, since I was not aware the body was somehow exempt from what I was taught are the basic rules of chemical reactions. But this is apparently the mainstream belief and to argue otherwise will only get you dismissed as someone ignorant of chemistry and basic physics. 🙁

    • RokShox

      My apologies for my crass comment. I was in the middle of conducting an experiment on ethanol metabolism.

  • Renaud

    Nice post, thanks.

    A lot of things would be way clearer if only we had things measured just after weight stabilisation phase.

    Maybe 1 month is not enough time to be fully keto-adapted, and adaptation could have be faster/slower depending on the preceding diet in the crossover (lots of questions arise from possible crossover effect too). This is equaly true for low-fat adaptation, and probably less for low GI (wich is very close to junk standard in mixing ratios of carb/fat). Anyway, 1 month is respectable and way better than 1 week !

    The study is good at providing interesting clues, and very good at raising questions.

  • Scott Russell

    Any thoughts on the (slightly) elevated cortisol levels? While this makes sense physiologically, I wonder if you have any thoughts on the long term implications, if any.

    • Another post…

    • Aaron H.

      They aren’t “elevated levels of cortisol.” They are reductions in cortisol that are just negligibly less than the reduction on the other diets. And with a p factor of just 0.05 it puts them right on the border of statistical significance.

    • My CRP and Cortisol went noticeably DOWN with LCHF… I’m very curious as to why the contrary was observed in the study.

      • CRP did go down in them, also. As far as cortisol, I’ll get into this later, but there are probably some issues with the timing of this.

  • Gretchen

    Two things that haven’t been discussed:

    1. The baseline was before the weight loss. So all results reflect both the effect of weight loss and the diets used for that weight loss as well as the different diets used during maintenance. It’s too bad they didn’t have baselines before each of the three test diets, but the study was complex enough and they might have figured they couldn’t afford that.

    2. LC diet resulted in burning an excess 300 calories a day, but there were no significant differences in weight. The 300 cal per day for 4 weeks would be 8400 cal during those 4 weeks, or, using the figure of 3500 cal per pound, 2.4 pounds. Now, daily weight often fluctuates by more than this amount because of fluid changes, so it would be difficult to detect in this short-term study. But is it also possible that the people on the LC diet, which carb-craving subjects might consider too restrictive, ate a few crackers or whatever and didn’t report it, despite the extensive efforts by the researchers to control intake. (This wasn’t a food-questionnaire study; all food was provided and researchers tried to make sure it was all eaten.)

    The detailed Methods are available as supplementary material for anyone wanting to delve into them.

    • Gretchen, I still can’t access the eMethods section on-line, just the “regular” Methods section, which isn’t giving me enough information. Your first point makes a lot of sense. The run-in phase, while still high in carbs almost certainly “cleaned up” the diets (e.g., no sugar). To your second point, duration really hurts us here. There is so much water movement in the first few weeks that’s it’s quite difficult, even with DEXA, to fully elucidate the changes in body composition. Kevin Hall has probably got more experience with this than most.

      Bottom line, a study like this needs be repeated with more subjects for a longer period of time. It’s going to happen.

    • Gretchen

      Peter, Is there a supplement other than “Data Supplement,” a PDF? I had no trouble downloading that.

      • Ahhh, the supplement link is working. I was trying to get it through the eMethods hyperlink, which was (and is) not…

  • Kurt

    Excellent analysis. The graphs are a great way of showing the nature of the results in a meaningful way for non-experts.

    I actually read the paper and found that as usual the mainstream media focused on incorrect interpretation of the rather insignificant minutiae of the CRP and cortisol levels rather than the main result. Part of the blame for in my view, is that the researchers used the minor differences in the inflammatory markers to form an opinion the the low GI diet was preferable to low carb high fat diet. Although I am not an expert, it appears that all markers are well within accepted normal ranges, and in particular, the post diet CRP figures were in the very low range for all protocols. The short duration of the study may also be a significant factor and a longer study may find different results over time.

    I was also pleased that you pointed out that there were variances in the REE and TEE response among he test subjects and you have correctly interpreted this as “individual results may vary”. However your graphical treatment of the means and SDs clearly shows the overall conclusion of the paper. Another well known “calorie is a calorie” blogger tried to cherry pick the individual results as proof that the overall result was not true.

    It will be interesting to see if in the not to distant future someone can put together a larger and longer study with the same level of quality and replicate the results.

  • Keith

    Thanks Peter. Really appreciate your work. Just a statistical quibble… The blue box actually shows the mean and the 95% confidence level for the mean rather than the standard deviation of the data which is much greater. One extreme interpretation therefore is the possibility of no effect for these parameters as I can draw a horizontal line through each of the blue boxes! That’s statistics for you! Also not sure whether the change in energy output was reflected in weight change or is that obvious?

    • Good catch, Keith! Thank you. Noted and corrected. Yes, this needs to be bigger.

  • lorraine

    As one who has read the study and has also been answering questions all week about it, thank you for an excellent discussion of the paper in this post. Your histograms greatly enhance some of the data (but don’t tell Dr. Ludwig I said so).

    I shouldn’t have been, but was, blown away by the media – and expert – interpretations of the CRP outcomes. For heaven’s sake is all I could say. They just cannot give it up on the notion that anything with fat in it is going to kill you with the big one, but quote a CRP outcome in another context, and all you’ll hear is how meaningless and non specific it is (my clients still fight with their doctors to order one). But here, LC increases your risk for heart disease because of clinically nonsignificant changes in CRP.

    I figured the MS biomarkers were a function of age. I think the oldest Subject was 40, and their exclusion criterion eliminated anybody who would have been on meds; ie, with disease. Speaking of which, it’s illustrative of just how hard it is to run a good study to examine their exclusions. They started their screen with almost 700 potential Ss to get a non-confounded group of 21. It doesn’t excuse all the bad science, but it does reflect on just how hard it is to get well controlled human studies. I hope this study can serve as a launch for another follow-up with bigger N’s and longer treatments (and older Ss).

    I noted your intention to speak separately about the thyroid numbers, but I didn’t think they changed all that much although on first view they do fit the trend that more carb in the diet requires more thyroid hormone. My thyroid numbers are ridiculous on VLC – TSH is down to .0016 – so much so that I won’t even show a doc! (But I feel awesome).

    Thanks again for all your work here. While all of your posts deserve widespread dissemination, this one is something that folks outside our little biology-geek club are talking about, and this post is really accessible.

    • Thanks, Lorraine. Hope you can share this with a friend next time they try to warn you…

  • Michele

    Dear Peter,
    “As difficult as it is to do excellent science, it turns out it’s even more difficult to interpret and communicate good science.”

    I can’t wait to see how NuSI will change that communication. I can’t wait because alone with the help of your blog, as well as your feedback on my little carbohydrate intolerance presentation, I managed to convince my father that the more he experiments with reducing or altogether eliminating carbs from his diet, the better he can control his type II diabetes. He’s due for a doctor visit soon to see if he can go from insulin shots to pills. Of course, it would be best if he didn’t need extra insulin at all but, for me, this a fantastic step in the right direction.

    Thanks for, at least on this small individual level, helping me interpret and communicate good science.

  • Joshua

    Nice writeup. I suspect confirmation bias on my part, but what struck me the most was the lack of perspective that most of the “news” articles had regarding the efficacy of the low carb diet in dropping weight. Even if there is slightly more inflammation in a low-carb diet, the health (mental and physical) effects of a lower weight are critical.

    I’d also like to know what kinds of food constituted the 3 diets. One of the things I’m hoping to see out of NuSI is the study of effects of different kinds of low-carb diets. It’s all about perspective though – I read a similar criticism of the study from a low-fat proponent who thought that the low-fat diet still had too much fat.

    • Yes, I was hoping to see this also, but as of my writing it the eMethods section was not up on the JAMA website. I’ll ask Dr. Ludwig when we speak next week.

  • Marilyn

    Thanks for this!!! All this is so very interesting and helpful. I don’t know what’s the answer to the “road ahead” thing. In my own small-town tiddley-wink world, I was once interviewed by the local newspaper. When the article came out, it bore no resemblance to what I had said. I learned two things by that experience: 1) never believe anything I read in the news, and 2) if the newspaper wants an article, write it out word for word and hand it to them. That worked pretty well for me here. Unfortunately, that’s not so easily done with the larger news operations.

    • Yes, I’ve unfortunately been reminded of this too often.

    • FrankG

      Denise Minger posted a cartoon relating to How Science Reporting Works… http://www.smbc-comics.com/index.php?db=comics&id=1623

    • Jillm

      Our neighbour was quoted in the local newspaper. He wasn’t even interviewed. He knew nothing about the article until a friend told him.

  • Victoria

    Did the subjects receive the three diets in different orders? If they did, I wonder if that had an impact on how they reacted to them. For example, if a person coming off of the run-in phase went on the low fat diet first, the increase in carbohydrate may have set them up for a different response to a low carb diet than they would have had if they went on the low carb or low GI diet first.

    • They did, and this is a good point. In fact, it’s quite likely that doing a low-fat diet after the other 2 would show a more favorable response than the reverse. This study was not powered to detect such an effect, though.

  • FrankG

    Many thanks for adding your reading of this significant study Dr Attia. It is a wedge in the dam of “a calorie is a calorie” and hopefully all agree that it merits further investigation.

    I particularly picked up on this paragraph… “Proponents of the Alternative Hypothesis argue that intake (i.e., food) plays a role on hormones and enzymes in the body that have a resulting impact on energy output, and even subsequent input. For example, eating one food over another can increase or decrease appetite, increase or decrease REE, increase or decrease AEE, and even impact TEF. While the effect on each of these may be modest in isolation, even small changes over the course of days can result in significant changes over months or years. …the sentence in bold (my emphasis) is I think, key to moving us forward. Too much of what is written seems to focus only what we ate at this meal, or how much energy we expended at the the gym today; without stopping to look at the bigger picture over many weeks, months or years. Yes I may consciously control what I eat at this meal — possibly even weighing and measuring everything like a good CICO follower — but in the long term my body makeup is a result of biochemistry, more so than of conscious behaviour.

  • Tim C

    Here’s an example of even worse science:


    The comments are priceless.

    • Ha! Tim, you’re stealing my thunder. I was planning to do the deep-dive on this one next week. Would folks prefer this topic or back to cholesterol?

    • Mike A.

      I’d like to vote for getting the cholesterol series to the finish line. I’m planning on seeing a cardiologist to discuss primary prevention and I want to be armed with as much information as possible. 🙂 My guess is that most of *your* readers are already suspicious of media reports on nutrition studies; however, I think your detailed explanations on cholesterol and related matters are invaluable and I haven’t found comparable resources elsewhere.

      There needs to be a support group for impatient Eating Academy readers.

    • lorraine

      Peter, you can title that post “Dreadful Science, Good Interpretations” given the comments left at the article. My favs are Dr. Yoni Freedhoff, “That’s. Not. Low. Carb”, and the quote attributed to ex-editor of BMJ “Medical journals will soon be wrapping up next week’s fish and chip”. Ha!

    • Keith

      Yes. Nice to see Zoe Harcombe go in with both barrels.

  • Colleen

    What, if anything, do you make of the fact that on the VLC diet protein was increased from 20 to 30%? Is this the logical result of eating more meat or something else? I’ve seen other commentary arguing this was an important factor on the increased TEE. Love the science and real analysis. Thanks.

    • It’s a good question, but I won’t know the answer until I speak with Dr. Ludwig (as far as why). I don’t believe, however, this difference resulted in the increased TEE, as Bray et al., failed to pick up this difference in their study earlier this year which varied protein intake.

    • Upping protein a little when doing very low carb is a nice way of keeping blood glucose levelled without resorting to extreme ketosis. They probably did this by design?…
      But I’m just as curious to find if that extra gluconeogenesis doesn’t show up in the energy charts.

      • They were not monitoring B-OHB levels, so I actually suspect the LC group was not in ketosis due to the protein load (about 200-220 gm/day) and even the carb load (about 90 gm/day). It would have been great to have seen a fourth (ketogenic) arm.

    • Andy

      Cortisol seems to be related to levels of dietary protein – see the following link http://www.ncbi.nlm.nih.gov/pubmed/6270500 Therefore it’s perhaps not surprising that a diet with 50 % more protein than the other diets (i.e 30% for the low carb, high protein diet versus 20% for the low fat and low GI diet) should have higher cortisol readings. Shame they couldn’t have limited protein in the low carb diet to 20% as well, thus minimising the likelihood of dumb press articles (if such a thing is ever possible……)

      • I’ll have to check this study out. Agree that they should have held protein constant across all 3 groups for sure. 20% for everyone and then all manipulation on F vs. C.

  • Sam Y

    Regarding energy output, is there a fourth category, food that is excreted but not digested?

    Is it possible that in a higher fat diets the body absorbs an amount of fat that is determined by some hormone/enzyme driven equilibrium and the rest just passes through?

    • Yes, re-read point 2, below:

      Furthermore, energy output can be broken down into four sub-components:

      1. Resting energy expenditure (REE) – the amount of energy expended to stay alive at rest (e.g., energy required for basic cellular function like ion transport and respiration)
      2. Thermic effect of food (TEF) – the amount of energy required to process and digest food (I also include in this category the amount of energy lost as undigested material in stool)
      3. Activity energy expenditure (AEE) – the amount of energy expended by exercise and non-exercise movement (I consider these as two forms of expenditure)

      The sum of REE, TEF, and AEE is called, appropriately, total energy expenditure (TEE).

    • I’ve always been curious as to how we regulate dietary fat absorption. We seem to do it so perfectly well, excreting the excess calories effortlessly, while the same simply isn’t true of carbohydrate.
      Unfortunately there are ample resources clarifying carbohydrate metabolism but I can’t find any detailing fat digestion and metabolism.
      Can anyone point me to a place where I can find out what happens to the excess fat we eat?

      • It depends on the type of fat and the hormonal environment. We can certainly store plenty of extra dietary fat under the “wrong” conditions.

    • Rob L.

      I am also wondering if the classic energy balance equation is flawed. Could energy that we consume be leaving the body in other ways? I ask this due to the following observations:

      *people on ultra-low carb, high fat diets often eat significantly more calories and still lose weight
      *excess glucose in the blood (and perhaps ketone bodies, I don’t know) are excreted in the urine ie. diabetics
      *there is a “fecal fat test” which leads me to believe that under certain conditions, fat is excreted in the feces
      *the claim that fiber consumption decreases the caloric value of a meal by 20%

      These are all additional methods that “energy” could be leaving the body besides fat production, exercise and basal metabolism.

      • This is all accounted for by the First Law. Read the previous posts I’ve written on this topic. TEF accounts for these changes. There is no magic if you draw the boundary conditions correctly.

  • Robert Newman

    hi Peter,
    Of course I want you to get into both topics, but I find the diet-composition stuff very useful in the Intro Biology class I teach. Students are interested, have all sorts of pre-conceptions, are often confused by conflicting “stories” they have heard, and this is a fantastic place to push them toward critical thinking, evaluation of evidence (or at least expose them to the idea that not all that they read or hear should be assigned equal value), etc. So my vote would be to continue with the diet composition theme to “flesh” it out.
    BTW, I actually ask the students to try to design a study that would allow them to test the effect of diet composition on weight loss. At least it gets them thinking about what things they need to be thinking about.
    Thanks for your very insightful communications.

    • Robert, your students are lucky to have you as a teacher. The great ones do what you’re doing — get the students to think, not regurgitate.

  • fatblond

    I look forward to the post on elevated cortisol levels. I wonder if it has something to do with the short duration of the the test phase, i.e. four weeks. On a lo carb diet your body is going through adaption to ketosis, which for new inductees can take a while. Your own personal history discussed this. As these were obese patients you can likely bet they were carb heavy prior to the test and not lo carbers. As a result, during the four week phase, their bodies were likely producing cortisol at some point for gluconeogenisis to raise their blood sugar until they were adapted to ketones. In a longer study, I wonder if the corisol levels would fall, remain the same, or if there is some other reason to have “slightly” elevated cortisol levels.

    • Absolutely. Robb Wolf has spoken a great deal about this. Very important point.

    • Afifah

      I too am dying to read your post on cortisol Peter.
      I am doing a series of public presentations on food and health and the next one is on STRESS. I can tell you, it is stressing me out more than the previous ones, as there is such a dearth of sound or detailed information out there regarding cortisol levels and the effects of various dietary factors.
      I am a LCHF faithful, and have been eating this weay for four years. The whole family has become entirely grain free and use animal fats and organic animal meats, eggs, dairy products and veg, but there is too little proper information out there for me to make any firm statements or recommendations regarding the effects of these foods on cortisol.
      And, would it matter what cortisol levels are, whether higher or lower than ‘standard’ patterns, if the individual in question feels fine and dandy and not flat or stressed out?
      I have been working on this all week and am still going round in circles.
      Love your work Peter, thank God for people like you, and all you other commenters, you all educate me, so thank you.
      Afifah (England)

  • Peter, as you know what any diet does to any plasma cholesterol level is potentially meaningless: more important would be what the diet does to lipoprotein particle numbers and with respect to HDL, what is does to HDL proteomics, lipidomics and functionality, none of which correlate well with HDL-C. Also CRP is a risk factor associated with atherosclerosis and other diseases but it is very still debatable whether it is a causal agent. The drug Vioxx or rofecoxib (removed from the market) significantly lowers CRP but is assopciated with atherosclerotic risk. So neither I or anyone else can conclude what the low carb CRP rise might mean in the long term

    • Excellent points, Tom. I just finished reading that LDL-P, LDL-C, hs-CRP study which reiterates this point. Will write about it in the next cholesterol post.

  • Hallie

    Please do more on this topic.

  • Don in Arkansas

    Dr. Attia, do a post on the low-carb, high protein study listed above. I drive way to fast to worry about cholesterol. 🙂

  • Cassiel

    Wow. Just wow. How is it that after all these years, and all these studies proving otherwise, low carb is STILL the media’s favourite whipping boy on just about every topic imaginable?

  • Joe

    Back to cholesterol!!!

    Pretty please?

    • David Nelsen

      With Xylitol on it!

      Don’t get distracted on LCHF vs SAD and not finish cholesterol.

      You’ll feel better once you put that one to bed.

  • Joe

    Thank you for your site. I have been in Ketosis for 3 weeks, have lost 14lbs, and feel great. Just have 2 quick questions:

    1. What are the effects of no-carb alcohol on Ketosis? (ex. Vodka)

    2. What are the effects of caffeine on Ketosis?

    • 1. Little impact on ketosis, but still leads to de novo lipogenesis in consumed beyond small/modest amounts.
      2. Not clear, but probably not significant.

  • my vote is to stick with this topic
    Thanks, Bill

  • Kim

    Swedish study next, please!

  • Ken

    Nice post, Peter. Also, interesting comments (I think) on same study by Phinney and Rosedale at: http://www.meandmydiabetes.com/
    Your observation of the lack of clinical symptoms in the ~30-years-old cohort is a good one, and important. Your colleague Tara Dall points out how long (years to decades, typically, after detectable lipid derangement) it takes before measurable hyperglycemia occurs. Having extensively studied the T2DM research myself, this delay is a well recognized and oft-demonstrated characteristic of the pathogenesis of hyperglycemia. The same goes for other chronic diseases, I speculate.
    The apparent irreversibility of so-called metabolic derangement (whatever this actually is) is a common theme in chronic disease. I think that it is probably developing in some of the 30-year-old’s, in different tissues for each individual according to genetic susceptibility. I think that it is fundamentally bio-energetic (i.e. mitochondrial) in nature. Possibly it is also partly a product of genetic aging that is unavoidable (i.e. hard-wired). A fair amount of damage probably has to accumulate before detectable disregulation ensues — the body is endocrinologically fairly robust in design (i.e. evolution) but not indestructable; we all die eventually. One theory of the fundamental cause of insulin resistance itself is via mitochondrial dysfunction.
    Possibly part of the problem with excess carb’s in the diet is a chronic overload of glucose metabolism, and that this is not evolved for and is relatively damaging over the long-term. Glucose metabolism seems to be more deleterious to mtDNA (and nuclear DNA) — hence, the difficulty or slowness of reversing damage in various tissues. These are prevalent ideas — not my own — but they seem to jibe with observations such as those in this study. They also jibe with the insulin/carb hypothesis, since these chronically increase glucose metabolism at the cellular level.
    The insidiousness of the early damage in chronic (or Western) diseases is generally underappreciated — it could help a lot on a societal scale to somehow mitigate this problem. But it won’t necessarily enhance revenues in the medical and pharmaceutical industries, unfortunately. I wish I had access to today’s tools (e.g. internet) and science at age 30.

    • Ken, I think your hypothesis is quite sound. There is clearly a time-exposure issue that makes this problem worse.

    • Bill

      Ron Rosedale’s perspectives are, as always, quite interesting.

      One of his observations is that properly designed low-carb diets tend to *decrease* metabolism, not increase it, as evidenced by such changes as reduced basal body temperature and lower free T3. Rosedale considers this one of the most fundamental benefits of his dietary approach, since it retards aging. He speculated that the increased energy expenditure seen in this study resulted not from the carb restriction at all, but from the gross excess of protein in the low carb diet that had to be burned by the subjects, a highly inefficient and thermogenic process.

      He also comments on the cortisol and CRP findings. He points out that cortisol, as an anti-inflammatory hormone, may be regarded as quite beneficial in many circumstances, as evidenced by its higher levels in centenarians and the animals on calorie-restricted diets who experience such prolonged lifespans. He clearly thinks it’s either cynical or ignorant to claim that the cortisol findings in his study somehow impugn low carb diets, even they are believable.

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  • CanuckCrossfitter

    Hi Peter,

    Thanks for another great writeup! I originally heard of this study from the NYT article, and had a thought in the back of my mind that you’d probably be writing an article about it at some point!

    I wanted to ask a quick question about the types of fat consumed in each of the three diets + run-in phase. Specifically, I notice that each of the diets have a slightly different ratio of SF to MUFA to PUFA, and I’m wondering how this might have influenced the study results. (Run-in was 1:2:1, LF was 1:1:1, GI was 1:2:1 and LC was 2:2:1)


    • Not sure about rationale, though it may be have a function of feasibility (i.e., how to get folks to eat palatable food a the prescribed ratios). Will ask.

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  • Richard

    Truly first class analysis of this much hyped study, however please ignore the Swedish one – it is not remotely worthy of your time – and instead continue with your invaluable cholesterol series.

    • The vote is so close!

    • jw

      I love the analysis of the studies, but have been anxiously awaiting the “payoff” on the cholesterol series.

      However, some of your responses to some of the LCHF elevated LDL-P questions makes me wonder if there actually will be a payoff. Of course, if it were obvious, NuSI wouldn’t have anything to do, so please either complete cholesterol or skip to the last chapter on it and fill in more detail later. My heart can’t take the suspense…

      (BTW, when you wrap up all of these posts into the inevitable bestselling book, make sure we grizzled old War on Insulin veterans don’t have to go to SD for a signed copy…)

      • Ha ha. I love it. Maybe the few who remember WoI will have special status…

    • Maryann

      I vote for the old name! TheWar on Insulin…and the defense of fat! It is passionate, intruguing, and counter-intuitive; I think it would make people so curious they would want to check it out. Yes, I guess you can tell who the original class members are…we’ll have to make t-shirts or buttons 🙂

    • Barbara

      I agree that the Swedish study isn’t worth your time. Those interested in reading more can look at the comments. They do a terrific job of exposing the multiple weaknesses of the study. The biggest mystery is why the BMJ chose to publish such a poor study.

  • Martin

    Thanks for the very informative discussion on this study.

    Remembering Gary Taubes’ NYTimes magazine piece of some ten years ago, which began with the image of nutritionists’ nightmare of realizing that all of their advice about a low fat diet was wrong, and remembering all of the scorn and derision heaped on Dr. Atkins by the medical community, it is understandable that people emphasized the high CRP results of the high fat / low carb diet and still cling to their previous advice about the low GI diet.

    By the way, the bad interpretation may not rest with the NYTimes and others, but with Ludwig himself (unless misquoted even in quotes) as the following excerpt from Marc Bittman’s article shows.

    [But not so fast; the “Atkins” diet also had marked problems. It raised levels of CRP (c-reactive protein), which is a measure of chronic inflammation, and cortisol, a hormone that mediates stress. “Both of these,” says Ludwig, “are tightly linked to long term-heart risk and mortality.”

    His conclusion, then? “The ‘Atkins’ diet gives you the biggest metabolic benefit initially, but there are long-term downsides, and in practice, people have trouble sticking to low-carb diets. Over the long term, the low-glycemic diet appears to work the best, because you don’t have to eliminate an entire class of nutrients, which our research suggests is not only hard from a psychological perspective but may be wrong from a biological perspective.”]

    The calories in / calories out restatement of the 1st law of thermodynamics seems to me do show just how bankrupt nutritional science has been on this subject of obesity. We despise economists, but none are so vapid as to tell us that the reason a government is running a deficit is because is spends more than it takes in.

    Surely the epidemic of obesity in our society presents a “prima facia” case that there is something wrong with our modern diet. It seems a ridiculous notion that the problem is simply that somehow we suddenly are a people with no self control exposed to limitless amounts of food.

    I wonder if the answer lies in human bacterial ecology, the microbiome. Researchers may find that our modern diet has evolved drastically in the recent past to include previously unknown foods like high fructose corn syrup, and that this diet has altered the microbiome in our gut, fundamentally changing our digestion. Some people more than others have suffered radical and harmful changes to their digestive system’s bacterial biome . Some changes are easily reversed to a more healthy state, others are not. Severe calorie restriction will always result in weight loss. But this idea of a changing biome in our digestive system suggests why some people have so much difficulty controlling their weight and why sometimes a corrected diet can restore health without the need for stringent calorie restrictions.

    The human body can sustain homeostasis throughout its many systems, and in a healthy body maintaining a normal weight should take as much effort as maintaining normal blood pressure or body temperature.

  • Howard nease

    Thanks for your analysis.

    If you’re counting votes, I’ll add mine for continuing your cholesterol series. I’m a practicing general internist, and have learned a lot, but still waiting to see how you approach treatment. One of my hardest decisions is when I’m faced with a patient, especially a woman, who is at low risk overall, but has moderately elevated cholesterol. I have a hard time committing to long term treatment with a statin when the absolute risk reduction is very small. I have started ordering the NMR lipoprofile, to better assess their true risk, but still look forward to your views on statins.

    Thanks for all the good info!

    • greensleeves

      Dear Dr. Nease:

      You are the first doctor I have seen in my entire life who appears interested in middle-aged women. OMG. Please tell us you practice in Northern California so we can come see you. I haven’t been to a doctor in 15 years since the last one told me “Just go to Weight Watchers. You wouldn’t have any problems if you’d stop eating like a pig.” Exact quote. At that time, by the way, I wore a size 10 dress, so I was at most 20 pounds overweight. Many many of the women here would beat a path to your door.

    • Another vote for the cholesterol series here. I already know that a calorie is not a calorie. 😉

    • Howard nease

      Dear Greensleeves,
      I am located in Tennessee, so it would be a rather long drive. Sadly, I do see women who have had similar experiences, and physicians who make comments like the one made to you are an embarrassment to the profession. Part of the reason I am more empathetic is that I’ve struggled with my weight since about 9th grade ( I’m in my 50’s). One of the reasons I am interested in the alternative theory, as Gary taubes calls it, is seeing how extremely difficult long term weight loss really is. I know my patients are trying, but their long term success rate is really poor. Our traditional weight loss advice just doesn’t work for most patients, which to me means we need to keep looking for better solutions. Best wishes to you , and please don’t judge all doctors based on that jerk.

  • Maryann

    My vote is for the Cholesterol Series 🙂 But do whatever makes you happy, Peter! Thank you again for all of your hard work! maryann

  • Martin

    And another question, Peter, if you will indulge me.

    In spite of my comment above, thank you for your explanation of the variables in energy balance. Energy input, what we eat, seems to be easy to measure. Energy output is much more complex. While REE is said to be the biggest factor, and AEE seems measurable, I often wonder about TEF, especially “the amount of energy lost as undigested material”. This seems to be glossed over as unimportant. Does the ick factor prevent researchers from collecting and analyzing the caloric content of all excretions? And if so how do we know that they are insignificant, especially cumulatively over a long period of time? How do we know that excretion of unneeded calories is not a factor in maintaining normal weight in healthy individuals?

    • I don’t think the ick factor plays a role. Historically, this “sink” of energy has not accounted for much variation. It is very possible, however, that such observations were made across a less dramatic swing of macronutrients. In other words, perhaps under the conditions of this study a greater change in TEF would have been noted.

  • bill

    Finally! Someone takes into consideration energy in stool. It’s got to be significant.

    My vote is for cholesterol series.

    Now, take 16 ounces heavy whipping cream (Trader Joe’s organic is good) with 2 ounces of Mascarpone cheese (a sweet cream cheese), add about a teaspoon of vanilla and a bit of cinnamon and whip till very stiff.

    I eat a couple scoops at a time with 1/4 of a banana, thinly sliced, or a few blueberries, or just alone.
    Nothing better. Ice cream can’t touch it.

    • bill

      Just wanted to clarify: Mascarpone has no sweeteners. It is sweet in the sense of not being tangy or savory like cream cheese.

  • Hi Peter, great article. Energy intake was constant for the weight-loss maintenance phase and the low carbers were burning more calories; do you have a theory as to why they didn’t lose more weight? 300 kcal/d should’ve made a noticeable impact after a month.

    • I’m trying to figure out if diet was titrated to TEF. In other words, they could have been matching intake to TEF to hold the reduced-weight constant. I haven’t scrubbed the supplemental methods to see if this happened.

  • I am not a huge fan of testing for the trend either, especially for what is essentially a mixture experiment. I would like to hear your thoughts on this before continuing with cholesterol.

  • Birgit

    Another delightful post. I’d love to hear about swedish women soon. 🙂
    I’m enjoying many opportunities to pass on the link to your blog. The starting point I give to a lot of people is your ” not pregnant” picture. But I”m pretty sure they’ll read more after that. 😉

    • I was looking for something on my computer yesterday and I found a picture of my from 2009, about 4 weeks after swimming from LA to Catalina Island. I was about 40 pounds heavier than I am now. I don’t even look like the same person.

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  • Ironmoon

    According to table 3 mean TEE was 3137kcal. 30% protein=235g and 10% carbs=78g.
    I’m not an expert but from everything I have read this macro split is good for gluconeogenesis = extra energy needed. Add high protein thermogenic effect to this and extra 300 calories doesnt sound strange any more.
    It would be interesting to see TEE with typical keto set up – max 30g net carbs and 1g protein/lean LBS.

    • Yes, just responded to another question with this point.

  • Oddly, the quote for the day I get out of this great article…

    PowerPoint without think-cell is simply a tool for torturing people.

    Oh yeah, the rest of the article about the whole sciencey bit is also good too. 😉

    • Think-cell is the greatest PP plug-in ever…

    • lorraine

      HaHa! Travis, me too! I went right to Think-cell before reading the rest of Peter’s post.

  • Jane

    Peter, when you see Ludwig, can you ask him whether the low-fat diet contained refined grains? It isn’t clear, and Don Matesz has argued from the fibre content* that it must have. This is very important in view of the possibility that the lower energy expenditure on this diet was due to oxidative stress in hypothalamic POMC neurons. White flour has had most of its (antioxidant) manganese removed and replaced with (pro-oxidant) iron. I realise all subjects were given a vitamin/mineral pill, but white flour + pill may not be the same thing as whole grains.

    *Matesz says ‘…This means that a 2000 kcal low-fat diet composed of whole grains, legumes, vegetables, and fruits could supply about 80 grams of fiber. Yet theirs supplies only 30 g of fiber…’

  • I vote for BMJ low-carb study too!

  • Paul

    Hello Peter

    Great work!!

    Where do you find the time?

    When will you update your blood work numbers? Your last update was July 2011.



  • steveo

    Thank you, Thank you, Thank you.
    The real take-home points are the scatter plots showing individual differences (humans are not identical bomb calorimeters), and the reluctance of conventional wisdom to consider that a low carb, high fat diet just might be good for health. And thanks for the Think-cell tip, I’ll give it a try

  • Michael

    “…Enter NuSI…”

    how about doing an overeating experiment, i.e. is it possible not to gain a significant amount of weight/fat by eating a ton of fat when there’s little or no carbs? It would be interesting to take for example a couple of Sumo wrestlers and turn their diets upside down, high fat / very low carb

    • We’re all over it. I like how you’re thinking.

    • greensleeves

      “is it possible not to gain a significant amount of weight/fat by eating a ton of fat when there’s little or no carbs”

      Why do we need to do an experiment on this? We know the answer: Yes. Absolutely. If you eat 12,000 calories a day and aren’t a Lance Armstrong, you will gain a lot of weight no matter what.

      The more interesting question is: if those 12,000 calories a day were comprised of 75% fat, how many could you actually bear to eat? If you go to Dr. Eenfeldt’s site, you’ll read about the butter experiment, where a couple of people tried to eat sticks of butter with a spoon. It doesn’t seem as if anyone can actually eat more than 4 or 5 tablespoons of butter at a sitting without making themselves feel kinda bad. They just naturally seem to stop.

      It’s very very very difficult to overeat fat. That’s the message, not that you can’t gain weight on it. Because of course you could. But if there’s enough fat in the diet, you’d naturally stop eating before you actually overate. And there have been studies on this, Taubes cites 1 of them in his books.

    • Michael

      greensleeves: “It’s very very very difficult to overeat fat. That’s the message, not that you can’t gain weight on it. Because of course you could. ”

      If you haven’t seen the Horizon/BBC documentary entitled “Why are thin people not fat” it’s available on Youtube and elsewhere. It’s an experiment in which young college students eat twice as much calories as before and some of them don’t get fatter. And they’re not on a ketogenic diet either. So getting fatter because one eats more energy/calories than their bodies’ energy needs, that’s not what happens 100% of the time.

      The energy balance model makes two predictions: 1. creating an energy deficit will make you lose body fat, 2. creating an energy surplus will make you gain body fat. The 2nd prediction hasn’t been tested like it should have been. That’s why it would be interesting to take a group of people and make them eat a big surplus of calories within a low-carb or ketogenic diet context and see what happens.

      • I second the recommendation to watch this series on BBC. Very interesting and highly suggestive of the individual variations that may explain why some LC eaters eat more total calories while others do not.

  • Tony

    I was hoping you would do a post on this! I first saw it in USA Today and then I went and read the actual study. Since then I too have seen constant media write ups twisting what the study found. I actually saw one article with the headline “Low-Carb diet may not be what the doctor ordered” and the sub-headline “Researchers discovered a low-carb diet may cause insulin resistance and cardiovascular disease”. The article then references this study! Unreal.

    As someone who works in a medical lab and runs CRPs, I find the barely higher low-carb CRP results to be insignificant…still within normal range. I’ll be interested to hear what you have to say on the urine cortisol and T3 results.

    They do mention TEF briefly under the COMMENT section (second paragraph down), they basically dismiss it as having little or no effect on the study.

    Great post!

    • I did a huge self-experiment 2 weeks ago and checked my CRP level 9 times in 3 days. Guess what the standard deviation was? 28%!!! Average value was 0.76 +/- 0.21. So, yes, lab error is a huge issue with any assay. Thanks for making the point.

    • Bill

      “So, yes, lab error is a huge issue with any assay.”

      Plus, isn’t it the case that CRP, and everything else doctors measure in labs, has some natural variation over time in each individual, as physiological circumstances and demands change? So snapshot measurements provide information, but certainly not complete information, even apart from lab error.

      And isn’t it also the case that while we’ve been trained to think of certain things like CRP and LDL as “bad,” in fact they are physiological and necessary? Apart from gross extremes, couldn’t a slightly higher CRP be quite healthy for a particular individual at a particular time?

      As I think I’ve mentioned here, my endocrinologist has concluded after many years that he has no idea what any particular person’s thyroid lab values should be, apart from obvious extremes. For one person a TSH of 1.5 may be too high, and for another too low. Couldn’t the same be true of CRP? Perhaps the very assumption that higher CRP is necessarily “bad” is mistaken, again holding aside gross elevation reflecting chronic inflammation.

      • Absolutely. This is especially true in the case of hormones like cortisol, which is why urine collection is preferred (assuming urine collection is representative of plasmas/tissue levels, which it may or may not be).

    • Tony

      A personal story for the CRP discussion….
      I used to eat the same popular whole grain cereal every morning for breakfast until I started noticing that I would get this horrible bloating abdominal pain about the same time everyday around midmorning. This went on for quite some time and, after I read Mark Sisson’s book, I started to suspect the whole grain cereal as the cause. During one particularly bad episode my CRP went from a baseline of 0.69 two weeks before, up to 19.85 the day of the terrible pain, to 6.38 the day after, and then back to normal not long after. Since I quit eating the cereal and switched to eggs or smoothies for breakfast I’ve not had the pain once in four years.

      My point is that what you don’t want is a drastically elevated CRP (means something acute is going on) or a chronically slightly elevated CRP like 3 or 5 mg/L, etc. (means you have chronic inflammation going on). Peter is the doctor, but to me the 0.09 difference between low-fat and low-carb diets is clinically insignificant and falls under “who cares”. We’re dealing with such small numbers, I could probably run a CRP 10 times on the same tube of blood and gets results that vary by that much. The results are still normal, indicating no inflammation, indicating no problem. Thats my take anyway.

      P.S. Being a cyclist and cycling fan, I liked the Zoncolan reference. I love it when the Giro climbs it!

  • Isabel

    Thank you so much for this timely post. Best and most rigorous interpretación of the JAMA metabolic study by far. I have been telling that to anybody that would care to listen and a to a few that would not… As for my vote for future posts? Do not ask me I want both! 🙂 And I cannot wait to hear your take on thyroid hormone and cortisol… Incidentally, I was just reading this study on dietary macronutrients content and it’s effect on metabolism:
    which Colpo mentions as proof that LC diets do indeed have negative effects on cortisol, and unless I am mistaken, the authors conclusion is the rather the opposite. Yes, LC diets do seem to increase cortisol, or rather counteract the dis regulation of cortisol common in obesity, but that seems to be a good thing. This is how the authors frame the study:
    “IIn obesity, the metabolic clearance rate of cortisol is increased in the liver (3), secondary to enhanced inactivation by 5?- and 5?-reductases (4) and impaired regeneration of cortisol from cortisone by 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) (5, 6). Enhanced cortisol clearance putatively leads to compensatory activation of the hypothalamic-pituitary-adrenal axis (7) to maintain normal plasma cortisol concentrations. In addition, intra-adipose cortisol generation by 11?-HSD1 is increased in obesity (6, 8, 9). However, the basis for dysregulation of cortisol metabolism in obesity is unknown.”
    Well, according to the results of this study, a very low carb diet seems to counteract the effects of this regulation of cortisol|:
    “These data show for the first time that chronic manipulation of dietary macronutrient composition influences glucocorticoid metabolism in humans. In obese men, an HF-LC diet increased whole-body regeneration of cortisol by 11?-HSD1 and reduced the rate of inactivation of cortisol by 5?- and 5?-reductases. As in previous studies, discrepancy between cortisol regeneration measured during dynamic testing and the more conventional index of 24-h urinary endogenous cortisol/cortisone metabolite ratios (Table 2?) reflects the confounding effects of 5?- and 5?-reductase activities on ratios of steroids excreted in urine. The increased 11?-HSD1 activity on the HF-LC vs. MF-MC diet was independent of differences in energy consumption and weight loss: the same effect was observed under fixed feeding (approximately isocaloric) conditions; and the MF-MC diet induced substantial weight loss without altering 11?-HSD1 activity. Moreover, the effect of HF-LC was already apparent after 1 wk of the diet when weight loss was minimal.”
    Ok, maybe I am totally mistaken here (I am an English/ Spanish major after all) and this study is not relevant at all, but it seems to me that ther maybe much more it the cortisol story that meets the eye.
    Thanks again for your blog. It is very much appreciated.

    • Thanks for sending over this study. Like you, I don’t find myself often persuaded by Colpo’s analyses (pleural) or interpretations.

  • Glenda Glass

    My vote is to continue the cholesterol series. I’m teaching a class on chronic disease prevention (low carb style) in August, and want to have the most up-to-date information to share with the audience. I’m on the edge of my seat waiting for the factors that influence LDL particle number.

  • kahn

    Again and again, simply awesome!
    Great many thanks Attia for taking the trouble to educate lay people like me on these confusing issues.

  • george henderson

    I second that; the Swedes aren’t worthy of your time, given what Zoe Harcombe and Denise Minger have already said.
    I’m gobsmacked that some bloggers – notably Colpo – are in denial about resting energy differentials. Whether or not this study proved it for once and for all, why wouldn’t they exist?
    Surely it is the more unlikely claim to make that all calorie sources are metabolized with equal efficiency at all times.
    just like all cars run with equal fuel efficiency, whether they run on diesel, petrol, or ethanol, I’m sure.
    Regardless of the type of sparkplug or whether timing is by distributor or computer.
    Because a calorie is a calorie, and a gallon is a gallon…

  • Jane

    We need to know whether the low-fat diet included refined grains. It isn’t clear, and according to Don Matesz its fibre content is lower than it would be if it contained only whole grains and no refined ones.

    This is very important in view of the possibility that the lower energy expenditure on this diet was due to oxidative stress in hypothalamic POMC neurons, which produce high levels of reactive oxygen species and were found recently to be damaged in obesity.

    White flour has had most of its (antioxidant) manganese removed and replaced with (pro-oxidant) iron.

  • Mark

    Absolutely fabulous summary of this article! I would just add one thought regarding the trend test and the over-hyped CRP result. The authors state that they “constructed a test for linear trend across diets, proceeding from highest to lowest glycemic load … assuming equal spacing.” It is straightforward to show that such a trend test boils down to a straight up pairwise comparison between the lowest glycemic load diet (i.e., LC) and highest glycemic load diet (i.e., LF). That is, the test does not include the LGI diet at all. This is counter to the analysis plan specified by the authors in which they said they wouldn’t even look at such pairwise comparisons unless the overall null could be rejected. It wasn’t for CRP, so this pariwise result should have never even seen the light of day. Saying this another way, the data presented in this manuscript provide NO EVIDENCE of any effect across diets on CRP.

    • This is a great point, Mark. I think the term “statistical chicanery” becomes that much more telling.

  • Jeff Johnson


    The study above gives some ideas on the apob test –

    Asked my Doctor for an NMR – he has me come see him in his office and he explains to me why my insurance (medicare and medicaid) will not pay for non-standard tests – visit was free of charge –

    My Doctor is an interesting impressive guy – he rides is mountain bike up this steep – mile long hill every morning on his way to work –

    So a week later – I call his office and ask for an apob test – he orders an apob and an apoa1 – they cost 34.00 each – will see if insurance pays for it –

    Anyhow – I would like help convert ing the pending apob and apoa1 test numbers into particle numbers –

    Dr. Davis said mulitply times 10 – the few examples I could find to look at – would suggest timing the apob mumber by 20 or even 23 to get an NMR number equivalent

    I want something (a coversion method) that’s reasonably accurate – as there is a big difference between timing by 10 or timeing by 20-23 ?

    • Such formula are decent approximations, but not entirely accurate. If your doc is willing to check apoB and apoA-I, that’s good enough. Don’t worry about trying to convert to LDL-P.

  • steve

    It has been my understanding that measuring cortisol levels can be quite inaccurate and the the best method to do so is salivary, not urinary which this study did. If correct, then the cortisol results are somewhat meaningless.

    • Depends what you’re looking for. Multiple cheek swab measurements throughout the day (say, every 2 hours) provides much more meaningful information about variation. Urine cortisol is sort of like taking the integral of the curve.

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  • pierre

    Peter I have been monitoring my ketone level with a NOVA Blood ketone test kit. So far I have registered .2, .9, .6, and .2 tonight. this is over the course of 5 days. Is this enough to consider myself in ketosis…meaning if I continue to see numbers jumping around like this for the next few weeks.

    Thank you

    • You’re flirting with it. You’ll ideally want to consistently be above 0.5 mM.

    • greensleeves

      Hi Pierre:

      Dr. Volek identifies the ketone sweet spot at 1.25 to 2.5. You can get there in just about 5 days. Try keeping your carbs to 10% and your protein to 18%. That worked for me. Jimmy Moore got to 2.5 easily by eating 12% protein and 3% carb, but he’s very insulin resistant; most folks probably don’t have to go so low.

    • Aviv

      I’m too, one of the unlucky ones… My body just refuse to go into full nutritional ketosis.
      I decided to track them for few days close to 5 time a day. Check if anything I’m eating is not helping.
      Even after dropping ALL dairy products and nuts, weighing my food, making sure I’m on the right ratio of macro-nutrients things are hard for me.
      I checked upon waking up, an hour after eating, 2 hours after eating and during the afternoon and evening. If I eat high fat meal (as I now always do) ketone level will rise a bit – I guess an indication I’m oxidizing the fat from the meal. Unfortunately the levels will fall down almost always during the day. When I’m feeling out of energy/sluggish I already know, it’s somewhere in the 0.3 -0.4… It’s almost as if I have a blockage to burn my own body fat, and during the day it will level out somewhere in the 0.4 range.
      I have some bad days and some good days, all depending on me Ketones level. Starting to really annoy me. I’m trying for 3 months now to be in a FULL nutritional ketosis, and I won’t give up until I’m there.
      One day I got so frustrated, I decided to do the following – check upon wakening and my usual 2 check up in the rest of the morning – 8am, 9:30am and 10:30am. Only this time I did not eat or even had coffee. Started with 0.7 and gradually went down to 0.4. Yet again.

      I am rereading Peter’s posts and comments again and again to see where is my mistakes, but can’t find it.

      Any advise or support will be highly appreciated.

  • Dan

    In looking at the media responses to this study, I’ll try to refrain from attributing their commentary to villainy, as it simply may be the result of stupidity, but sometimes you gotta wonder if there’s an agenda…

  • greensleeves

    Btw, my vote is to finally say how/if a low-carb diet can lower your LDL-P. Bonus points if you give general eating advice for those with 1 APOE4 and 2 APOE4s.

    • We’ll get there soon. Do you mean 1 apoE2 and 1 apoE4? If so, you’re probably about the same as the “wildtype” with 2 apoE3 copies.

    • greensleeves

      Hi Peter:

      “Do you mean 1 apoE2 and 1 apoE4?”

      No, sorry I was unclear – actually I mean 1 APOE4 (heterozygous) or a double APOE4 (homozygous). 2 people at my job recently got their gene test results back and were shocked to learn that they have the APOE4. One woman is 45 and learned she was an APOE 3/4; the supervisor is actually rather scared to learn he is 4/4.

      They both now believe they are hopelessly doomed to Alzheimers no matter what they do, so naturally they do nothing. Kurt Harris would tell them to go to 85% fat; but I think the conventional wisdom is that they have to go vegan ASAP. More and more people get these tests, learn bad news and really don’t know what to do. They end up paralyzed.

      If you could offer general advice for people like this, I think it would help many. Is low-carb part of the general answer or not? Ty!

      • All things equal, two copies of the E4 allele carries about a 20x higher risk of CVD and a higher risk of Alzheimer’s disease, though off hand I don’t know the risk multiplier. E3/E4 carries about a 5x increased risk of CVD. Again, I don’t know off hand what the risk increase is for Alzheimer’s disease. The E2/E4 is probably a wash, as the increased risk of the E4 is roughly offset by the presence of the E2 allele. Of course, the (very rare) homozygotes for E2 seems especially immune to CVD.

        I do not believe that even the case of homozygosity for E4 (about 1% of the population) ensures CVD or Alzheimer’s disease. I would agree with Kurt Harris. When I work with people who are homozygous for E4 I have a very special “plan” for reducing their risk of these diseases. And, yes, low carb is a BIG part of it.

  • Great post doc! Anthony Colpo should read it. Not that anyone should care what he writes, but he is fond of insulting Dr. Eades and making mince meat of the issues: http://anthonycolpo.com/?p=3680. And real men allow comments on their blogs. You’ll see what I mean by that if you read his blog.

    Question: You pointed out some outliers in the study – one that increased TEE on a low fat diet. You said to this “be willing to self-experiment until you find what works for you.” Are you suggesting that, for that individual outlier and thus for millions of others like him (or her), that a low fat, high carb diet is more healthful? I’m not talking likes or dislikes here. I love bagels and pizza but they turn my knees into grapefruits. I’m talking physiological health.

    Again, great post!

    • Fred, it’s all about how you define the experiment. When I experiment with my diet — keep in mind, a few years ago I went vegan for 6 months long before experimenting with low carb — I do my best to fully define the outcomes (e.g., body composition, disease risk markers, performance, mental acuity).

    • David Ma

      Interested to know how you defined the outcome of mental acuity?

    • David Nelsen

      I read a few posts on Colpo’s site and he comes across as some sort of Internet tough guy/blowhard. I didn’t necessarily disagree with everything he has posted, but he seems to be cut from the Jim Rome school of journalism. It seems he has a book or two to sell and just doesn’t come off as a serious man of science to me. Especially so when you compare his posts to those of Dr. Attia or Denise Minger as an example. Denise uses humor but in the right way IMHO.

      • I read one of his posts a few months ago which really intrigued me. I started to write an email to him, but as I read more of his site I realized this would likely generate a nasty interaction, especially as I was writing to question his interpretation.

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  • Brian

    Dr. Attia,

    I’m on my 4th week of eating <20g of carbs a day and I love it. I do have a question though.

    I understand that the whole thermodynamics argument should be applied as the physical explanation or definition of how fat accumulates, and that the reason for fat accumulation is "carbohydrates are driving insulin driving fat". I understand that when our body decides to accumulate fat, we eat more BECAUSE we are accumulating fat. However, we still have the ability to feed ourselves more than our body might need, just as we have the ability to (at least try) starve ourselves regardless of what our body is asking of us.

    So if I'm eating barely any carbs (<20g), and very little protein (<150g) and I eat as much fat as I can possibly eat without getting sick, and then I sit on the couch all day, regardless of how much energy I feel like I have, what happens to the fat? Will it be store? Is there another fat regulator in our body in the absence of insulin? Or at a certain point will enough fat even cause high levels of insulin to be secreted and therefore store it. This is obviously a exaggeration. It may have been easier to just ask, "Can/do you still store fat on a ketogenic diet and how would this process work?"

    • If you are in ketosis, but still consuming more energy than your body can dispose of through the 3 (or 4) means by which we dispose of energy you will gain weight! At some point — and it will differ for different people — your body will not be able to “dispose” of the extra energy (albeit from fat intake, not protein or carb) through increased REE or TEF. At this point, you will start to accumulate fat.

  • george henderson

    Differential weightgain on isocaloric diets with identical macronutrient ratios:


    FASEB J. 2012 May 25. [Epub ahead of print]
    Timed high-fat diet resets circadian metabolism and prevents obesity.
    Sherman H, Genzer Y, Cohen R, Chapnik N, Madar Z, Froy O.

    Although timed HF-diet-fed mice consumed the same amount of calories as ad libitum low-fat diet-fed mice, they showed 12% reduced body weight, 21% reduced cholesterol levels, and 1.4-fold increased insulin sensitivity. Compared with the HF diet ad libitum, the timed HF diet led to 18% lower body weight, 30% decreased cholesterol levels, 10% reduced TNF-alpha levels, and 3.7-fold improved insulin sensitivity. Timed HF-diet-fed mice exhibited a better satiated and less stressed phenotype of 25% lower ghrelin and 53% lower corticosterone levels compared with mice fed the timed low-fat diet.

    A 12% advantage over low-fat mice and an 18% advantage over ad lib high-fat mice…

  • george henderson
  • Ken Peters

    If a R/Q is .70 on a high fat low carbohydrate diet does that imply an increase in the VO2 max by an equivalent ratio? Ken

    • No, the RQ only speaks to the breakdown of substrate of utilization.

  • Ulrik

    Hi Peter & fellow eating academics,

    Did you see Bill Harris’ latest lecture on LecturePad on n-6 fatty acids? I just watched it, and now I’m quite puzzled: for a while I’ve heard that n-6 PUFAs are bad, and should be limited. Now I see this research that suggests otherwise. The problem is that most of the cited evidence is either observational or in non-humans, although with some RCTs toward the end. What did you think?

    I noted that when Harris talked about blood lipids it was in terms of total/HDL-C, or LDL-C; it would of course be more interesting to know the relationship between LA and LDL-P!

    • Bill has become my teacher on this topic, and I’ll be doing a series (don’t worry…it’s won’t be nearly as long as the cholesterol series!) on PUFA, where I’ll cover this topic, and others, in great detail.

    • steve

      i saw this too, and it is confusing. I have thought that if LDL-P is at goal than the amount of sat fat in the diet is not relevant. Was also under the belief that polys have a greater chance of oxidizing and if they comprise a large % of lipids that via any number of particles enter the artery wall, a greater chance of an inflammatory response may ensue. Will be glad to hear Peter’s take on this when he gets to it before we all start substituting poultry for meat!

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  • Sharon

    Saw this response to the JAMA study in the NY Times: http://www.nytimes.com/2012/07/10/health/nutrition/q-and-a-are-high-protein-low-carb-diets-effective.html?src=recg

    Gina Kolata still towing the “calorie is a calorie” line, finding an obesity expert to tell us low-carb is just hocus-pocus. After reading the article, I wonder if Dr. Hirsch even read the study. The period when the dieters were on weight loss was a standard low-cal, moderate carb and fat diet. So, Hirsch’s comment about losing water weight does nothing to explain why the TEE went up on a very low-carb maintenance diet. They didn’t lose weight, that’s why it’s called maintenance. Given my own experience, I wonder if their body composition changed? Could a higher lean body mass explain some of the increase? I can’t find any body comp numbers from the maintenance phase.

    • Look for Dr. Ludwig’s response. Unfortunately, Dr. Hirsch really got a number of *important* details wrong.

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  • Dorian

    Hi Peter,

    A few questions that I’ll post in different comments (and if my etiquette is off, please redirect).

    First, I like your choice in colors on the pie charts — Green (good) for Fat, and Red (bad) for Carbs. Was this intentional? 🙂

  • Dorian

    Next, not my idea, but haven’t seen this comment on this post: With a range of 300 kcal/day difference in TEE, one would think that would have an impact on weight at some point. After only 28 days (and 8400 kcal total), I suppose that 2-3 pounds of weight loss wouldn’t really be significant/meaningful — is this your take?

    Instead of a 4-week phase, a 4-month phase (120 days and 36000 kcal) might produce a weight difference of 10 pounds — which might be significant and meaningful, wouldn’t you think?

    • Correct. The delta in TEE over such a short period of time is the reason they did not report on weight changes. Let me point out, they DID see trends in weight changes according to the differences in TEE, but they were not statistically significant over such a short period of time.

    • And More

      Also, there is no reason to expect that changes in REE and TEE occurred immediately after the diets changed. One should reasonably expect that any accruals of body mass differences would be attenuated significantly , both up and down, during the periods of metabolic adaptation to each new diet. Combine that issue with routine variations in body mass due to variable water retention, the small sample size, and the short durations of each diet.

      Yet, some comments in other forums criticize the study because differential weight loss results were not reported. Such comments are not reasonable criticism of this particular study.

      • There were differences in weight, but they were not reported because they lacked significance. Had the study been longer than 4 weeks, it’s quite likely it would have shown significance.

  • Dorian

    In your discussions with Dr. Westman about whether people on ketogenic diets with high LDL-P may not have the same high risk as the rest of the population with high LDL-P, it seems to me that such a ketogenic diet could be called a confounding variable. Regardless of the label, being in a ketogenic “state” seems like only one of many possible “states” where the global model (correlation) may no longer hold. For example, perhaps in a “low sugar, high low-GI” state, the model doesn’t hold, or perhaps in a “high sugar, high fat” state, the model doesn’t hold (perhaps *under*predicting risk).

    I think what makes this particularly interesting (and personal to each individual), is that given a Bayesian prior of a certain state that an individual is in, and given their LDL-P (or other biomarker), how does that person’s risk look once these states are considered.

    I get that studies (observational and clinical?) do make adjustments for gender, age, smoking, etc., but I suspect these are more (linear) regression oriented than they are state oriented (or even quintile- or decile-oriented).

    In a hypothetical (and extreme) study, it would be great to somehow do a mathematical cluster analysis of what millions of people actually ate, clustering them into say several dozen clusters — and then assess risk by cluster. So, if I happen to eat a “fastfood: burger, fries, but only water to drink” cluster, I might have one set of risk; while if I was in an “Eenfelt LCHF” or a “WheatBelly” cluster, there would be different set of risk.

    This last paragraph leaves me wondering, given the Bayesian prior of what I eat (and maybe who I am), how much can general population studies really help me improve my health (unless of course, I’m the poster boy for the population tested)?

    • Yes, I agree. Ketosis is but one state where the model is less applicable. Technically, any state other than the state where the results were generated would call into the question the dogma.

  • Dorian

    Peter, thanks for the replies. Just got my Health Diagnostic Lab results back 🙂 , and there is a 30 mg/dL between the Non-HDL-C (calculated) result and the LDL-C Direct. On previous posts, you’ve described all the cholesterol carrying particles, but is this difference (typically) mostly attributed to VLDL-C or a combination?

  • Martin

    Hi Peter,
    Have you seen this in the NYTimes? Much worse than anything Bittman might have written. Of course someone who has been researching obesity for nearly sixty years might not want to admit the errors of past ways. I had to fire off an e-mail to the author, Gina Kolata. Maybe Gary Taubes could speak with his sometimes colleagues at the Times and give them a tutorial.



    • Yes, pretty strange (and shockingly incorrect). Gary and I, for unrelated reasons, were speaking with David Ludwig today. I suspect he’ll be writing a letter to the NYT to, at the VERY least, correct the huge errors in this response to Gary’s op-ed.

  • lorraine

    Yes, Gina’s at it again over at the Times. A friend sent me a link. I almost didn’t open because I feared it was her saying something stupid again, but I did and it was. Surprise that they’ve turned off comments. I sent her this email:

    “You’re kidding, right? You accepted the notion that there was magic in that study because people on low carb lose water weight? First of all, any water weight loss would have happened months ago in the initial stages of weight loss, PRIOR to being randominzed into the treatment arms. Secondly, it was a weight maintenance study!!!!! Nobody lost any weight once they were randomized into the treatment arms. The purpose of the study was to see if different diets protect better against weight regain during maintenance. Did you even read the study for heaven’s sake?

    Non-scientific people who are trying to be well and lose weight send me your blogs all the time for comment, and without exception I just roll my eyes and have to spend time correcting the misinformation you put out there.”

  • Adam

    Martin, I also saw that response by Dr. Jules Hirsch. After doing some research, it seems that Gina Kolata (and Dr. Hirsch) is one of the entrenched “calorie-is-a-calorie” establishment. They have a long-running feud with Gary Taubes dating back to her amateurish review of his book Good Calories, Bad Calories back in 2007.

    the following blog post by Dr. Michael Eades explains the rift, and explains the ridiculous “study” that they keep referring to:


    I agree with Dr. Attia here, Dr. Hirsch’s way of denying the results of the recent study (because it doesn’t match his decades-long crusade) is shockingly wrong. Peter has more knowledge of this in his pinky finger than I do in general, but even I read it and was like “that makes absolutely no rational or biological sense whatsoever”. it was a sad attempt by Dr. Hirsch as he doubles down on the wrong side of his cognitive dissonance.

    the worst part is that it’s getting so many reads in the NYT… again muddying people’s minds with false and discordant information.

  • lorraine

    Correction to my previous post and email to NYTimes:

    Ms. Kolata,

    Earlier today I wrote you regarding my frustration with your representation of the above referenced study. I see, though, that I erred in believing that I was being sent a blog post by your colleagues who do “Well”. I apologize for that error, but the level of badness of this piece by you sounded just like the Well blog. I should have been tipped off to my error by your inclusion of Hirsch, who IIRC, is often your go-to guy on your dietary pieces, but I missed it. I would think that Hirsch would be particularly interested in the findings of Ludwig, as the increase in energy expenditure found in the LC group – some to a greater level than previous to weight loss, would address one of Hirsch’s foundational problems with dieting; that is, the difficulty in sustaining weight loss due to reductions in energy expenditure imparted by that weight loss. That the two of you discussed this study as though the findings related to the weight loss itself has left me and others in the field dumbfounded.

    • Is there a place to post this on their site? Look for David Ludwig’s correction, also.

    • lorraine

      No, Peter, there are no comments turned on for this piece (wonder why). The only way is via email to the writer. Dr. Ludwig’s response will probably be handled as a letter to the editor.

  • g2sb

    A paper that nicely documents a very interesting dietary hypothesis has recently appeared on Dovepress from Ian Spreadbury of Queens University, Canada. It posits that inflammatory microbiota of the small intestine are promoted by the dense acellular carbohydrates (e.g. sugar and grains) in western diets, and that this may be the primary cause of leptin resistance:


    • It’s interesting and I don’t doubt that gut flora changes with carb consumption thus inducing some problems — ulcers, for instance, peridontal disease, etc. — but the question is whether this is the *mechanism* that’s driving obesity (i.e., fat accumulation). It’s an extra layer of complications over the endocrinology and metabolism. I realize it’s currently very interesting to hypothesize inflammation as the cause of insulin resistance, but it is still difficult to find much experimental work linking inflammation to insulin resistance causally. The two are certainly associated. The other point to keep in mind, the author seems to be trying to get dietary fat involved based on rodent experiments, but I don’t think what happens in rodents is particularly relevant to humans. Pick a different animal model of disease — pigs, for instance, or cattle — and you get a different environmental trigger of the obesity/diabetes phenotype.

      So certainly inflammation is involved, and I have little doubt that our diets make it worse, but I still think this is an additive problem and not the primary driver. Of course, what I think vs. what someone else thinks is irrelevant. Until we start doing the right kind of clinical trials in humans, we might as well be discussing religion or politics.

    • g2sb

      Thank you for the thoughtful reply.

      An important condition to add to your list of ulcers and periodontal disease – before any “etc.” – is the LC diet’s impact on GERD. Before transitioning an diet to LC four months ago, for the previous decade I had not been able to make it – at an extreme max – beyond 48 hours without a dose of Prilosec. About a month ago, I was able to easily end this PPI dosing cold turkey, using only a few doses of sodium bicarbonate during a 10 day transition period. Since then I have had zero GERD symptoms and my rate of weight loss now seems to be even faster.

      Is my now functioning stomach acid system engaging with my gastric biosome, thereby reducing related inflammation, thereby reducing leptin resistance, and thereby further reducing my appetite? Heck if I know. All I do know is that my appetite seems to be significantly further reduced.

      • I don’t know either, but I know some scientists who have the tools to study this rigorously, and I hope to get them involved in NuSI studies.

  • Dorian

    Peter, while statins are used to lower cholesterol, we as have learned that LDL-P is more important than cholesterol, so where does this leave statins? Do statins have an impact on LDL-P? Or maybe more importantly, is the best mechanism for lowering high LDL-P the use of statins? Does the HMG-CoA reductase process that produces cholesterol also produce LDL particles? If so, that would be pretty convenient.

    • Will be addressing in Part X… (hopefully the final installment).

  • perry

    Hey man I enjoy your blog.
    about 5 months ago i made a effort to get into better shape. I am 6’1 tall and weighed close to 230lbs. I joined a gym and and cut all sugar (the best I could) out of my diet. I then started lowering my carb intake .In about three months I dropped to 195lbs while continuing to increase my strenght. a Right now I eat only good carbs and consume allot of protein. My goals are to get stronger in the power and olympic lifts. I do HIT training about three times a week and weight training about 4 times a week. Im thinking trying out a ketosis state. I am wondering would ketosis (and the limiting of protein) be smart for my current goals of increasing strength? Or should I keep up a moderate carb count and higher protein count?

  • Joe

    NY Times discussing the study.

    • Joe, “discussing” is putting it mildly. This is called journalistic sloppiness at its finest. Virtually all of it is incorrect, and Ms. Kolata didn’t even fact check it with Dr. Ludwig. Keep an eye open for his response.

  • Gustavo

    Dr. Attia, was referred to your site last night and am now hooked! I was wondering if you were aware of any diminishing-returns effects of low-carbohydrate diets? Weight-loss seems to be quite drastic in those with a waistline of, say, 36-inches, but do you think someone carrying 8lbs of ‘extra’ fat will have difficulty losing it on a diet alone? I know Gary Taubes talks about losing weight without exercising but he doesn’t address this particular issue.

    • Very tough to say without knowing a lot more, Gustavo. Sure, you’ll typically see a greater response in those with more fat to lose, but this is not a universal truth.

  • Chris

    Let’s talk about the statistics for a minute. You mentioned chicanery regarding the CRP and PAI-1 in your post, and you are correct. They’ve done 3 stat tests here: the overall difference test (a necessary, but limited, test – tells you that there are differences across groups, but does not tell you which groups are different from which); if the overall difference test is significant, they did post-hoc pair-wise tests of every possible pair-wise comparison (3 in total: lc v. lg, lc v. lf, lg v. lf), using a Bonferroni adjustment, which is fine; then this trend test. It is not clear how they constructed that trend test, and they do not provide enough info in the paper to judge the validity of the test (this may be obfuscation, or perhaps just lack of attention to detail).

    As might be expected, the devil is in the details, more specifically, the footnotes in Table 3. They report the p-value for the overall difference test, and then the pair-wise test results are reported in footnotes b and c. You’ll see that for several outcomes, the low glycemic diet does not differ from either of the other 2, but presumably the low carb and low fat diets do differ. You can verify this by comparing means for a particular diet to the CIs for the other two diets – generally, if the mean for one is *inside* the CI for another, then they are NOT different from each other (statistically; though sometimes, if the numbers are close, you’ll get p-values of 0.03 or 0.04 or so). This is your basic, ANCOVA-type approach for analyzing experimental data – you compare the groups of interest to see if they differ. The trend test seems inappropriate here, even though we don’t really know how it was constructed. Sounds like they tried to force what may have been up to 6 different sequences of diet progression into an artificial, single sequence trend, which doesn’t seem appropriate.

    Now lets look at the tests that matter with respect to PAI-1 and CRP: PAI-1 improved in each diet when compared to baseline; however, the groups simply do not differ from each other, despite the borderline significant ‘trend’ effect (which is essentially meaningless without some more information about how it was constructed). You’ll note that the means for each diet all overlap with the CIs for the other 2 diets, and the overall effect is not even significant. Furthermore, CRP did not change relative to baseline (all the diet means are inside the baseline CI), for any of the diets; AND, more importantly, CRP does not differ across the groups, even in terms of the far less stringent overall difference test (p = 0.13). For the authors to call out this effect in the Comment section discussing CRP is kind of silly; for the press to obsess on it is simply ludicrous.

    I look forward to your post on cortisol though, because that one did indeed appear to look the worst for low carb.

    • Mark

      Hi Chris,

      Good points, but actually we *can* know exactly how they constructed the trend test and precisely what it is testing (see my comment on this from July 5). The authors state in the paper that they “constructed a test for linear trend across diets, proceeding from highest to lowest glycemic load … assuming equal spacing.” The last part of this is hidden in the footnote for Table 2. This test is conducted using a contrast in a linear model, where a contrast is simply a linear combination of the model parameters (in this case, the model-estimated means for each diet) such that the contrast coefficients sum to zero. In this case, the appropriate contrast coefficients for testing linear trend with equal spacing are -1, 0, 1, or any multiple thereof (e.g., using -0.5, 0, 0.5 would lead to exactly the same test statistic). That is, the contrast for linear trend takes -1 times the mean for the LF diet, 0 times the mean for the LGI diet, and 1 times the mean for the LC diet… this is just a pairwise comparison between the LF and LC diets! But the authors said that they wouldn’t do such pairwise comparisons unless the overall null hypothesis could be rejected, which was not the case for CRP. AND, they said that when they would do pairwise comparisons, they’d use a Bonferroni correction… they didn’t for CRP. As such, their data provide NO EVIDENCE for a difference between diets with respect to mean CRP. None. They should never have even discussed this, per their own pre-specified analysis plan.

      • Mark, thanks again for very good explanation of this issue.

  • Martin

    I have to admit that this idea of the microflora in the gut and their effect on obesity is one I have been wondering about a great deal. I really think this concept makes an important leap to explain several unanswered questions in the obesity debate.

    With DNA analysis we are now becoming aware of the role of the literally trillions of bacterial cells that inhabit our body most of which were previously unknown because they cannot be cultured in the lab.


    One important question is that we always speak of peoples genetic differences in their propensity to obesity, but humans of different races, for instance, have a genetic make up that is more than 99% identical. What about the genetic make up of the human biome? Here we can perhaps have important species completely wiped out by an improper diet. While human genetics may vary only slightly the human biome could vary greatly between individuals. Further, as the above reference article points out, the beginnings of the human biome are passed from mother to sterile child at birth, creating a kind of quasi-heredity.

    And as in the bacteria that cause dental caries, the article referenced by g2sb above (thank you!) points out another very interesting idea. The insulin/obesity connection does not consider that in the paleo diet, or the diet without processed foods, all sugars, fats, carbohydarates or proteins are found within cells and not as pure compounds. This goes beyond such notions as the glycemic index as the abstract points out. The thesis questions whether the flora in the gut can be considered “the forgotten organ” and an organ that is susceptible to being radically changed by our diet, especially pure sugars encountered outside of cells, for instance. This I think goes beyond just the notion of inflammation.

    Peter, thank you so much for tolerating and even reading my posts. I am aware that they sometimes verge on rants, and I certainly do not want you to feel I am trying to hijack this very important forum.

    • Martin, your insights are great and add to a great discussion thread. Thank you.

  • Martin

    Peter, the mention of gastric ulcers above in the thread reminded me of the story of Barry Marshall and of what you are up against in your battle to overturn years of bad science. I guess your extreme regimen of diet and exercise might be considered by some as analogous to drinking a Petri dish containing cultured H. pylori.

    • Yes, this example is one of my favorites — and resulted not only in a Nobel Prize, but a fundamental way a disease was treated. Unfortunately, this was (and is) a much easier problem to treat, as it’s simply treated by a single pill.

  • Chase Webber

    In the same topic as this I would value your investigation on the latest Prospective Cohort Study: Low Carbohydrate-High Protein Diet and Incidence of Cardiovascular Diseases in Swedish Women. I seems they have neglected to factor in for a Low Carbohydrate-Moderate Protein-High Fat Diet?

  • jw

    Hopefully, it is not against protocol here to note that Gary Taubes is featured on this week’s EconTalk podcast:


    (I am sure it is great, but I won’t have a chance to listen to it for a few days…)

    I figure that this only fair as it was Gary’s original interview on EconTalk back in November:


    That was the AHA! moment for me and led me to read his books and eventually discover Peter’s site.

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  • Corrie


    I have been reading a lot of research articles about the effects of hormones on the body at the cellular level (as well as Good Calories, Bad Calories) and their effects on lipoprotein lipase in storing fat in adipose tissue. Research by a woman named Greenwood talks about how when progestin is added to Zucker rats the LPL activity on the fat cells increases. Does this mean that women who are on birth control that contains progestin (or progesterone) will likely have difficulty losing weight even if on a low-carb diet? Insulin would no longer be present to shuttle the glucose/fat/protein to the fat cells, but progesterone’s affect on LPL (the gate keeper to the cells) might combat the gains that could be made on a low carb diet. I ask because I have been doing the low carb diet for 5 months now, 20-25g of carbs daily with an increase in fat in the recent months (cream cheese, coconut oil, etc). Granted I am 5’11 and weigh 150lbs (where I should be for my BMI), but I would like to tone up and lose the excess fat. However, my weight has not budged and I was curious to know if it had to do with the progesterone in my birth control? Do you know much about other hormones’ affects on fat metabolism?

    • Corrie, the effect of hormones on LPL is significant as you note. The effect of E and P on LPL (in addition to insulin’s dramatic effects) may partially explain fat differences in men and women, and pre- and post-menopausal women. However, there could be many reasons to explain the lack of weight loss. Figuring it out would require a lot more detective work.

    • corrie

      I read through your personal testimony and read about your results. Did you notice once you began a more drastic Carb restriction that it was difficult to slim down in your abdominal area, or that it took longer? Since you mentioned that’s where your body chose to store fat. How long did it take to get to the waist size you are now? Do you think there is a set point for everyone as far as weight goes? Maybe there’s a certain weight that your body likes and doesn’t want to lose anymore fat? Or is there always room for improvement on a high fat low Carb lifestyle, it just requires a more strict restriction of carbs, or possibly resistance or weight exercises added with it?

      • I think there certainly are set points. It’s taken 3 years to take 5 inches off my waist in a manner I deem “sustainable” for me, and it has not been a monotone decrease, either. There are many plateaus, of course, so you’ve got think LONG term…as in a lifetime of change and tweaking.

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  • Hi Peter — Thanks for the great review of the study and engaging comments. It didn’t look like anyone had posted the response to the Kolata article by Drs. Ludwig and Ebbeling in the above comments. Here it is:


    • Thanks very much for this, Andrew. Kind of amazing that NYT would run a LOOOONG piece on this featuring someone who hadn’t read the paper *without* contacting the author of the study…then only give him 150 words to respond. Better than nothing, I guess.

  • Has anyone considered the worlwide impact of these diets on the Earth? Can we support this for everyone or are we just talking about an elite class that can personally afford these menus along with our big screen TV’s and iPhones? Are there other healthy options?

    • Lots of folk have, but largely with incomplete and inconsistent science. I think this is an important question, but it is a distant second place to the first-order question: what should we be eating to be healthy. If we don’t know the answer to that, what difference is sustainability? These issues get confused too often.

    • Yeah, that’s a fair question, Keith, and it’s one I seem to hear a lot from family and friends. Like “well, there’s not enough land on earth or air in the sky for all the animals we’d need and methane they’d fart out if everyone ate as much meat as you, John” Sustainable choices are things I want to consider as I continually tweak my diet, but on the other hand, I also don’t want to be that guy who says “Yeah, sure, LCHF with lots of animal proteins/fats is better for you, but it’s not sustainable…so let’s keep eating stuff that makes us obese, gives us heart disease, diabetes, cancer and kills us prematurely. After all, that’s more sustainable. You see my struggle?

  • Peter. Thank you for this and your work. Simply fantastic.

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  • tcseacliff

    great articles. just also read the cholesterol blog. just got home today with my new heart stent due to a clogged artery (plaque). Now , how do I now continue to convince myself, my doctors and family, that despite needing this stent , which really came at a shock to me. discovered the blockage when i increased my exercise regime. I am s. fla and am not feeling like I will get any help maintaining a low-carb, high protein regimen . how do I get my doctor on board with me ? immediately the statins are out and have been read the riot act !

    • Not sure. I guess you hope they are open minded enough to learn new science.

  • tcseacliff

    I am encouraged by seeing medical people like yourself actively involved . maybe when it goes more mainstream, it would benefit all of us, you have the advantage of access to the proper tests of true measure of health, not some cookie cutter formula and knee jerk “standard ‘ test’s we all get shuffled into.
    my breakfast in the heart wing this morning was scrambled egg with a piece of pound cake?? oatmeal?? lunch was something breaded , white rice, margarine? how are we to get /stay healthy when this is their idea of “good eats” for me? it is maddening ! hope to get some support, feel like , now my life REALLY depends on it!

  • Pamela Brink

    I found this statement confusing: “Not surprisingly, the low fat group experienced a significant reduction in HDL-C. It’s been documented many times that dietary fat raises HDL-C and dietary carbohydrates reduce HDL-C.”

    If dietary carbs reduces HDL-C, why is it “not surprising” that low fat reduces “HDL-C.” Sorry for the confusion.

    • If you lower fat, what do you add to make up for it? 🙂

  • Joe

    Just a minor statistical quibble: when you say “The blue box shows the mean change (middle of the box) with the 95% confidence interval above and below. The height of the box is therefore two standard deviations.” shouldn’t the last part be “two standard errors” (i.e., SD / sqrt(N))?

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  • Hans Laestander

    The 1000 dollar question should maybe be: “WHY do people (researchers, the media) often try to angle their conclusions towards the angle “Low Carb Is Dangerous” even though the data says something else?” Is it (putting on my tin foil hat) the Sugar Lobby? Or is it just the old Fear of Fat that lingers on? This is something I haven’t seen anybody discuss.

  • Joe

    Great article as usual peter. Bad science is rife unfortunetly. A British doctor called Ben Goldacre has written 2 book on this topic (Bad Science & Bad Pharma I think)

    He also dids a great 14 minute TED talk last year. Here is the link if you are interested:

    Keep up the great work and fight !

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  • Celeste Kelsey

    I am very interested in your futher comments on TSH, T3, and Cortisol. I am almost 4 months into a Ketogenic Diet – initially started to support my husband who has Type I Diabetes and is having great success with his BG readings. I have Hashimoto’s Thyroiditis and while my lipid profile (done two months into diet) was excellent by all standards…my TSH was low (and went lower still); my T3 was low; and my 24 hour urine Cortisol was high. I am seeing my endocrinologist next week and coincidentally came across this post. Would love some info in hand when I see her.

    Your quote from above article:
    “Because I know some of you will ask, I will comment in a subsequent post on the changes seen in TSH, T3, and cortisol. These topics deserve a post of their own.”

  • Mark Hoheisel

    Just a notion about a experiment.

    One of the things I’d love to see highlighted in an expertimental design is a stunningly important distinction between low carb weight loss diets and effectively everything else…which is that everything else is calorie or portion limited and low carb is classically ad libitum within accepted foods. The importance of this is glossed over in designs that compare the results of weight loss diet regimens. Since these designs take each regimen at face value the critical fact that one group is forced to eat less than it chooses and the other is not is rendered unimportant.

    The two buffets experiment:

    One nice resort or cruise ship…6 weeks, two different kinds of buffets 3 weeks each.

    Participants get a free long resort vacation with all food free in exchange for agreeing to a lot of testing and monitoring (which is designed to be as unobtrusive as possible.)

    Participants aren’t allowed to bring in any food. All food is provided at the resort’s buffet which is open much of the day. Participants are not made aware of the purpose of the study. Various resort activities are also provided and activity is monitored.

    One buffet is designed by Dr.Attia, one by a well known representative of the mainstream…say Dr.Ornish. Each side has control of the menu and presentation…but of course no control of what or how much any participant eats. Participants are not in any way told to restrict their eating…other than the control inherent in the fact that the only food is at the buffet…eating is completely ad libitum. Both Attia and Ornish menus strive for food variety, quality and presentation over the entire study that meets appropriately high resort standards.

    One of the things measured is what everybody eats and how much. I picture a scale with a camera that takes a second to register who, what and how much.

    Participants activity levels are measured and everybody gets several full physicals with bloodwork…etc. hey it’s the price of a long free resort vacation.

    The study is interested in the the effect of diet composition in an unconstrained completely ad libitum setting on physiology. There is absolutely no effort to seek weight loss or any other outcome…the only variable is the buffet.

    Half the period is Attia buffet, Half is Ornish buffet. Three weeks each. Everything remotely reasonable about the participants is monitored.

    If the Alternative hypothesis is correct, the nature of the choices in the Attia buffet will have a significantly different impact on the participants than the choices in the Ornish buffet. Since the partipants are not “dieting”, not seeking to lose weight and in fact are unaware of what’s being studied…no distortion is introduced by one experimental group being restricted while the other is not. The same participants are exposed to both buffets for an extended period allowing within subjects tests.

    If the Attia buffet has lobster tails in butter, flilet mignon, asparagus and hollandaise ….and the participants entirely at liberty choose to eat less of it…would the lipid hypothesis – calories are calories – folk say it was because it was was so boring and unappetising?

    • Mark, that’s a very elegant idea. If the low carb cruise had better results (just focus on weight loss), there would be at least 3 NOT mutually exclusive explanations:
      1. They consumed few calories (perhaps because they were less hungry; for others, perhaps “bored”)
      2. They were more active, either deliberately or spontaneously
      3. In a lower insulin environment, they increased lipolysis relative to re-esterification and this was manifested by an increase in REE (a la David Ludwig’s JAMA paper).
      Of course, any combination of the his would work, too.

  • Mark Hoheisel

    I think it could provide pretty solid data about 1 and 2.
    People in AI resorts typically wear little ID bracelets anyway. In this case they are bit bigger and have a QR code on top and a little pedometer/pulse reader on wifi. There are workers standing there to help in the buffet anyway…they monitor and assist with the simple protocol which is every time they get a new plate of food they put it on a convenient scan station. The station weighs it subtracting the weight of the plate, scans their bracelet and takes a photo of the plate. Later people follow a protocol to enter data about foods and portion weights…and the menu data has exact nutritional numbers for each dish. When they are finished the plate is run through again to subtract the uneaten portion. It’s not accurate to the microgram but it’s a pretty fair aproximation of what every participant is eating which is a whole lot better than many designs.

    The pedometer/pulse reader provides constant data and of course it’s used with a lot of detailed data about each particpant…height, weight, age, etc. That would provide a pretty decent metric for activity level…not calorie by calorie but decent.

    As towhat they were thinking…for a lot of reasons it would be good to have an experimental psychologist in on the design. A worker with a ipad taking daily surveys…if well designed could go a long way to answering that. They would just seem like obsessive consumer satisfaction surveys. Less hungry or bored ought to show up pretty clearly in a good design. It’s not that subtle a psychological question in this context.

    Neither of these data streams are very intrusive. Most casual observers would barely notice them. The devices and coding are pretty basic stuff cobbled together out of common cheap digital devices.

    One potential confound is if particpants have some idea what’s actually being studied…and if they have some existing opinion or bias about the outcome. This is another reason for experimental psychologists. This can be detected and dealt with.

    One odd possibility is that the study could make some extra money to help reduce expenses …and help provide a layer of misdirection at the same time. This kind of captive audience is used by both companies selling stuff and market reasearchers. You could sell an hour or so a day of your captive audiences time to outsiders. This would provide a very plausible cover story misdirecting attention away from possible confounds if participants have an idea what’s really being studied. A hour a day of focus group or timeshare condo sales and nobody would be looking for further explanations of what’s really going on.

  • Mark

    Pardon if my comment makes no sense, great article btw… I’ve posted about this study and a rather smart guy mentioned how he didn’t like the study. For one stated that the DEXA results “went missing” or something like that. Do you have any updated thoughts on this study?


    • They only did baseline DEXA. No subject had follow up DEXA due to the short duration of the study. Nothing went missing. It was never intended. The follow up version of this study, which will be much longer, will include this and more.

  • Mike

    I have recently started on a ketogenic diet after seeing one of your youtube interviews. The area of concern I have is with flow mediated dilation (FMD) studies conducted with various fats. How does that square with CVD risk?


  • Mike

    The testing Vogel has done using FMD seems to indicate that a high influx of fat causes inflammation in the blood vessels…at least temporarily. Apparently it takes several hours for the vessels to return to their normal cross sectional area. If one is regularly consuming saturated fats (as I am now) do I need to worry about chronic inflammation at each meal?

    • You’re going to have to send me the exact paper Mike. I get about a hundred “what do you think of this” emails a day. Hope you can appreciate writing this blog is the lowest priority of my life (family > NuSI > training > …. > blog). If I’m going to spend a minute answering a question, don’t make me chew up the minute looking for the paper.

  • Mike

    Here is the paper http://www.ncbi.nlm.nih.gov/pubmed/9036757 and thanks for taking the time to respond.

    • I don’t get this journal without paying, so can only read abstract. Not able to comment without really understanding this methodology. I’ve never found studies like this to be especially helpful, unless they can be translated to meaningful outputs.

  • Mike R

    This study seems to portion the blame of this observation on high levels of serum triglycerides which overall as I have observed personally and from what other people and studies have demonstrated seems to dramatically decrease on a High Fat low Carbohydrate diet.

    • That’s certainly a problem with it, since there is no debate in the literature (or all practical experience) that isocaloric replacement of carb with fat decreases TG and raises HDL-C. There may be a 1-5% exception to this rule based on apoC-III deficiency. So out of the gate this seems odd. Perhaps there was something else in the meal? Perhaps the technique is measuring an artifact? Perhaps this effect is so transient as to not be clinically meaningful? Or maybe it’s all true. Who knows.

  • Mike

    It seems they introduce carbohydrates into the testing that I have seen i.e., bread with olive oil. In any case, I intend to proceed experimenting with LCHF (into my 2nd week). I will test my ketones with a meter and also get my blood tested for the parameters that have been discussed. My previous HDL level was 34 (TCL = 140) based on a mostly plant based diet. I expect an improvement there. Thank you for such an informative site!

  • Lisa

    Hey all,
    Not sure where else to add this, but I’d be interested to hear your thoughts on this ‘news’ piece regarding gut bacteria/obesity.
    Have you read/explored this area at all?

  • I thought of this thread and the NuSci initiative while reading this article in the WSJ today… http://online.wsj.com/article/SB10001424127887323398204578488290293116774.html?mod=WSJ_hp_EditorsPicks
    Fascinating that there is a huge debate going on regarding fluoridated water but very little (if any) science! We’ve been doing this for 50 years but I’m not sure we can definitively answer the question on the pros/cons of ingesting fluoride for tooth decay. Conclusion…we need more NuSci-initiatives.

    Also for those that missed Dr. Attia last weekend…

  • Mike

    I found a free journal that cites a number of references to flow-mediated dilation (FMD) as a means of assessing risk from diet. http://animalscience.psu.edu/files/pdf/AT03-6-1-03.pdf .

    Here is a reference that indicates that reusing cooking fat as opposed to using fresh fat may increase risk http://content.onlinejacc.org/article.aspx?articleid=1125686 .

    Fatty acids increase vasodilation http://content.onlinejacc.org/article.aspx?articleid=1126611 .

    Many low fat proponents use FMD as their supporting logic. These sources would suggest that the topic is open for debate.

  • Amy

    I found your blog this morning, and I’m trying to wrap my brain around it. It’s pretty hard to think of going against the grain in terms of diet and healthy eating in popular culture. I am wondering… I’m not heavy. In fact, I would be classified as thin by most people. I think perhaps I could lose some fat based on my (somewhat inaccurate, likely) body fat scale, but it’s not apparent to most. I run long distance, am 44 and my cholesterol was very low a few years ago– in the range of “too low,” although I haven’t been able to find out much about what that could mean. My blood pressure is always low, as is my resting heart rate. Last year, I found out that I had anemia (since corrected with supplements) and my that I needed levothyroxine, as well. About 10 days ago I ran another ultramarathon, and in my recovery quest I began wondering about inflammation and healing, which is how I found your site. What I’m wondering is… do you think that a person who is not trying to lose weight and who typically “carbo loads” prior to races (and, truth be told, other times as well) is also going to see particular health benefits as well with higher good fats and low carbs? I felt like I had a fairly healthy diet (low added sugar, fruits and veggies) but not I’m wondering if I could be healthier, faster and have less creakiness in recovery if I considered upping my fats. It has never occurred to me. I have had what might be arthritis in my left hip for about 3 years, and so I deal with that kind of inflammation (?) off and on. I’m becoming suspicious that I have followed the wrong path in eating less meat and saturated fats and more carbs. Ugh. It’s not a good realization.

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  • Jennifer

    Dear Dr. Attia

    I was an obese 180 at 5’4″. I had always been fit and slender, competed on the swim team, spent hours in the gym, etc… At about 29 years old I started to develop a layer of fat that no amount of stair master would burn off and over the years the layer got thicker and thicker so by the time I was 40 I was obese, had no energy and was depressed all the time. I went to doctors who gave me the whole-grain, avoid red meat and fats mantra and I believed them. When my blood numbers started going in to the high risk areas of cholesterol and triglycerides I got really frightened. My dad’s family doesn’t seem to survive to 60, most are obese and dead of heart disease and cancer. I put everything I had in to diet and exercise and went back three months later. To my horror the numbers had gotten worse and I hadn’t lost any weight. The doctor said that maybe I was cheating and not recording the cheats. He looked at me like I was a liar. I really did not know what to do. Luckily, my type 1 diabetic cousin came to stay with me to help while my husband was ill and he brought with him a mountain of information about insulin; what it is and does. It took a few weeks to pound it in to my head but I eventually decided that maybe there was no reason not to try this “paleo” diet but went against everything I knew. We went through my pantry and he explained about glycemic indexes and we ended up throwing out most everything. The first month was horrible but after 6 months I had dropped 35 pounds and my blood numbers fell to normal ranges. I now don’t even look at bread and I automatically scan menus looking for whole fish or chicken etc… I continue to improve.

    This is a testimonial I am sure you hear often but really only sets the stage for my actual question. How do you avoid the anger towards the establishment? I feel like I was deliberately poisoned for profit. I am losing nearly all respect for the food and medical communities, especially the FDA. People at work ask how I lost weight. I tell them organic paleo diet. Veggies, fish, meat, eggs, nuts, etc… I tell them I dont watch fat calories and I practically drink coconut cream (god I love that stuff) and eat avacadoes almost every day. They say “but that is so unhealthy”. One lady said she couldn’t go on that diet because she was a type 2 diabetic and her doctor recommended a whole grain plan. I feel like I am spiralling into a very black rage. You are at the epicenter of all this and you see and know more than I do. How do you look at all these sick and dying people that are being lied to by “experts” and not feel the anger and helplessness? A quick investigation reveals these concepts were know over a hundred years ago but basically buried and discredited by lobby groups for wheat and corn growers, sugar, soft drinks and edible oils industries with major representatives sitting on the boards at the FDA. The science may not be “finished” but its not like there isn’t any. That type 2 I mentioned recently fell over because she got disoriented with vertigo and has lost sensation in her feet. She hit her head on the way down and was in the hospital for 3 weeks where they probably stuffed her full of bread and orange juice. How do you maintain your sanity?

    • To your last question, Jennifer… I’m not sure, but having folks you like to commiserate with sure helps. Thank you for sharing your story with me and the other readers.

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  • Richard S.

    Peter –

    The lesson I take from this study, if I care about REE or TEE, is not that I should be on a low-carb diet. There’s too much individual variation for that to be the logical conclusion. Rather, because of that variability, I should conclude: (1) that diet can be important, (2) that it might be important for me, and (3) that I should personally test different diets to find out.

    If I were trying to create a food pyramid for everyone, then the averages are important. Or if I were buying food for the Army, then perhaps I should let the average effects guide me. But otherwise, who cares how the diets affect others? I’m not eating for them. All any of us should care about is how each diet affects us, individually. (I suspect you agree.)

    In other words, here we have researchers hoping for nice, tight data — with large variations between groups and small variations within groups. (Nothing like a home run, with both statistical and clinical differences. Of course, as an individual I should be fine with that too — so long as it gives me important information I can use.)

    And I suspect researchers are frustrated when the opposite happens — when large variations within groups make the between-group differences statistically less significant, or insignificant. No researcher likes unexplained variations. But sometimes these unexplained variations can be just as valuable to us, as individuals.

    Take this study as an example. What if we had the same individual variations, but the between-group averages were the same (no difference at all in the averages among the diets). It would be absurd to conclude that the diets had no significant effect on REE or TEE. On the contrary, the logical conclusions for the individual would be the same — that diets can matter, and I should find out which diet works well for me.

    To summarize my point: In their fervor to find statistical differences (e.g., between/among groups), are researchers sometimes missing the more important clinical (or I want to say “personal”) significance their findings might have to us as individuals?

    I suspect it would be hard to draw those conclusions with this study, from the individual’s perspective, if they hadn’t used a crossover design. Then the differences might remain completely unexplained.

    As NuSI takes on similar studies, I hope you consider using crossover designs whenever possible. In a sense, it doubles the opportunity for important findings. (If the differences between groups are not statistically or clinically significant, then the differences within groups still might be, when viewed from the individual’s perspective.)


  • Kaur Garšnek

    Thank you for this post, and keep up the good work!

  • Brad L


    Long time follower of your blog. Thanks for al the work and continuous education that you provide. Just finished reading “The China Study”. Would you be able to point me in the direction of some objective interpretation of this study. I found the author to very biased through the read and I am looking for some other perspectives to say the least. Thanks.

    • Best appraisals I’ve seen of the China study (not to be confused with The China Study) are by Denise Minger and Mike Eades. Easy to find on line if you search their names and content.

  • John

    Hey Pete,
    When does a journalist begin to provide a disservice to his/her readers?
    When he picks up the pen!

    All kidding aside, I really appreciate the objectiveness in the work you’ve been doing with NUSI.

    • Fortunately there are some good ones out there.

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  • Karuna

    Thank you Peter for your phenomenal knowledge and interpretation. I am learning so much from your posts. Not only about the content of the study, but also the deeper terminology used in studies. I will be sharing this in the community and the MDs in my family. Onwards and upwards my friend!

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  • Kristin

    I was wondering when you might be getting to the subsequent post on the changes seen in TSH, T3, and cortisol. I just found your blog today and can see I am going to very busy reading. Very appreciative of all of the information here as it is put together extremely well. Thank you and again I am looking forward to reading your posts.

  • Eli

    Is it possible that there was an agenda behind the analysis and policy recommendations? Where nefarious or not, it seems that they research and ignored or discarded research has been selectively interpreted and exaggerated to push a carbohydrate diet, hard to believe this was accidental, as there is big money to be made in the large scale production of various carbohydrate products.

  • Kay

    I’m trying to find information about LCHF for gestational diabetes. I’d love to see this kind of analysis of this study http://care.diabetesjournals.org/content/early/2015/07/27/dc15-0515.abstract. (I realize that 40% carbohydrate is not very low carb.)

  • Rex Field

    I read this per a friend’s suggestion. I have absolutely no idea what I just spent the last 30 minutes reading. Back to my oatmeal.

  • Dave

    Hi Dr. Attia, insanely useful blog, thanks so much! Can you comment or link me to the blog you mentioned you would cover regarding the T3 TSH etc of this study?


  • Bill

    Hey Peter,

    I have been having weight loss success on a ketogenic/VLCHF diet (I find it relatively easy to stick to) and seem to share your phenotype. But it seems to me that the author of this study continues to push the GI index as well, saying “LCHF is too hard to stick to long-term” and “most people do not need to restrict carbs to this level to see weight loss.” What do you think is the scientific truth in both of those statements? There is a new book where low-GI carbs are reintroduced in phase 2 after a LCHF beginning phase. I counted on Amazon a significant number of people who reviewed the diet negatively, saying it didn’t work for them. My hunch is that (for most of the ones who followed it properly) the diet’s failure was the reintroduction of significant carbs, regardless of GI. But you’re the doctor, so I defer to you on the issue…

    In your experience do you think most of the human population can tolerate a reintroduction of low-GI carbs and maintain good bio markers/weight loss or is this once again “missing the forest for the trees,” and carbs must be limited overall, regardless of GI, for a dominant subset of the population?

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  • Michael

    Hey Peter –

    Did you see the Ioannidis article in JAMA July 26 , 2016? Some very interesting reflections on the whole Theranos case. I was surprised by his take on the issue of self testing. Sometimes more and more data can be a problem .

  • Jim Turner

    Hi Peter,

    What do you think of Stephan Guyenet’s take on the study? — http://wholehealthsource.blogspot.com/2016/07/nusi-funded-study-serves-up_6.html


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