New JAMA Article Supports the Metabolic Advantage of Low-Carb Diets

Effects of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance


Is a Calorie a Calorie in Our Body?

The Journal of the American Medical Association published an important study today further assessing the “calorie is a calorie” dictum of the dieting world. As there are three main controversies in this world: politics, religion, and calories in=calories out, the authors must be congratulated for taking on such a controversial task. The study is only a preliminary report, but the findings are exciting.
In this study, Dr. Ebbeling and her group took 21 participants and placed them on 3 different isocaloric diets with different macronutrients1. They initially underwent a 7-month run-in diet for weight loss. They then were placed on a 4-week conventional low-fat, low–glycemic index, or very low-carbohydrate diet along with undergoing a variety of tests. What separates this study from the masses is their measurement of resting energy expenditure and total energy expenditure in the participants.
They also assessed leptin, thyroid stimulating hormone (TSH), triiodothyronine (T3), urinary cortisol), insulin sensitivity high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, plasminogen activator inhibitor 1 activity, C-reactive protein (CRP), and ratings of hunger and well-being.


The results were interesting, though not surprising to many low-carb advocates. During the run-in phase of the study, the participants lost an average of around 30 pounds, which corresponded to 13.6% of their baseline body weight. Body fat percentage decreased from 33.6% to 29.1% and daily energy intake during the test diet phase was 2626 calories. 
However, the meat of this paper (pun intended) was the resting energy expenditure findings. Resting energy expenditures represents the amount of calories required by the body during a day of non-activity. The higher the energy expenditure, the more the body burns throughout a day. Therefore, in terms of achieving weight loss or maintaining decreased amounts of adipose tissue, the higher the resting energy the better.   

Resting and Total Energy Expenditure:

All diets showed a decrease in resting energy with weight loss, but the difference between the diets was statistically significant. The decrease in resting energy was least in the low-carb diet and greatest in the low-fat diet. Values were -205 (calories per day) for the low-fat diet, -166 for the low-GI diet, and -138 for the low-carb diet. Those of us that have switched to a low-carb lifestyle have all experienced this firsthand, especially those of us that have tried calorie restriction and felt our energy levels plummet to nonexistence.    
Total energy expenditure revealed similar results, decreasing by 423 calories per day for the low-fat diet, 297 for the low-GI diet, and only 97 calories per day for the low-carb diet. Basically, these results show us that weight loss on a low-carb diet leaves the dieter with a body that continues to burn more calories than other diets. In other words, a low-carb diet leaves the body more metabolically demanding than the other diets – i.e. it leaves the body with a metabolic advantage.

Other Variables Observed:

  1. Leptin: a hormone that controls appetite and is associated with inflammation and cancer2-6 was found to be significantly lower in the low-carb dieters. 
  2. Insulin sensitivity: another major risk factor for cancer induction and recurrence7-11 was highest in the low-carb dieters.   
  3. Cortisol: a glucocorticoid hormone that counteracts insulin and the body uses to raise blood sugar when it is low via stimulation of gluconeogenesis (conversion of fat to glucose) predictably rose in the low-carbers.
  4. Serum TSH and T3: these thyroid values were the lowest for the low-carb diet, which is expected and has been shown previously.
  5. Serum HDL: “good” cholesterol was significantly higher in the low-carbohydrate diet versus the others.
  6. Serum triglycerides, which are associated with cardiovascular disease, stroke, and cancer12-15 were significantly lower in the low-carb group versus the other two. 
  7. Plasminogen activator inhibitor 1: it has been found to be increased in cancer and even predicts for cancer metastases16, obesity, inflammation, and the metabolic syndrome17-19, and was reduced in the low-carb group.
  8. CRP: C-reactive protein is a marker of inflammation and has been correlated with poorer outcomes in cancer, stroke, depression, and cardiovascular disease20,21 and was increased in the low-carb group.
  9. Hunger and well-being: did not differ between the trials.



No study is perfect, and as is often the case in dietary studies, this one had its fair share of issues.  The study was short term, with each diet consumed for only 4 weeks. This plagues many dietary studies, but due to the inherent cost of these clinical trials, we often encounter such issues. Also, physical activity was measured with accelerometry, which is imperfect. The other typical dietary trial criticisms (measuring methods, etc.) apply here as well. 

In Conclusion:

The inflammatory serum marker C-reactive protein (CRP) was increased in the low-carb group, and unfortunately this has made the headlines in many reports. This finding has been shown before over the short term, and longer-term studies have shown a low-carb diet to reduce inflammation, as previously discussed. Also, leptin and plasminogen activator inhibitor 1, which are also associated with inflammation were significantly elevated in the other diets versus the low-carb, so from this data it is difficult to decipher which is the most inflammatory short term. Once again, I will defer to the long-term data. Conversely, all markers of metabolic syndrome were improved in the low-carb diet, which is consistent with the ever-expanding literature22-28.
Directly comparing a low-carbohydrate versus a conventional low-fat diet, though short term, showed that the low-carb diet resulted in a resting energy expenditure that was 67 calories per day higher and a total energy expenditure that was 300 calories per day higher, even though physical activity did not change during the study. Therefore, the low-carb dieters appeared to simply burn more calories per day than the other two dieters. This parallels other reports on the “metabolic advantage” of low-carbohydrate diets29-31 that lead to so much controversy in the field of nutrition. However, for those of us who have been following this diet for years, we have witnessed this first hand, often with effortless weight loss. The exact cause for this is unknown, but is likely interplay between hormones and our body’s inherent storage versus burning capabilities and mechanisms, which cause it to view fats and carbohydrates as different sources of fuel.
It is well established that weight loss results in a decrease in resting energy expenditure, i.e. as you lose weight, your body burns less fuel (calories, fat, etc.) and this is often the reason why as patients lose weight, it becomes more difficult to continue a diet. This is also why telling a patient to markedly reduce their calories while increasing their activity is so difficult to adhere to32,33, rarely works, and merely sets them up for emotional and physical failure. This also is why telling a patient to eat less and exercise more (especially when based on a low-fat diet) is not a dietary strategy, but rather torture.  
Keep eating like a caveman, keep curbing those carbs, and keep watching the studies pour in to support this lifestyle.



1. Ebbeling Cb SJFFHA, et al. EFfects of dietary composition on energy expenditure during weight-loss maintenance. JAMA: The Journal of the American Medical Association. 2012;307(24):2627-2634.

2. Cirillo D, Rachiglio AM, la Montagna R, Giordano A, Normanno N. Leptin signaling in breast cancer: an overview. J Cell Biochem. Nov 1 2008;105(4):956-964.

3. Fantuzzi G, Faggioni R. Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol. Oct 2000;68(4):437-446.

4. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395(6704):763-770.

5. Garofalo C, Surmacz E. Leptin and cancer. J Cell Physiol. Apr 2006;207(1):12-22.

6. Hekerman P, Zeidler J, Korfmacher S, et al. Leptin induces inflammation-related genes in RINm5F insulinoma cells. BMC Molecular Biology. 2007;8(1):41.

7. Goodwin PJ, Ennis M, Pritchard KI, et al. Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol. Jan 1 2002;20(1):42-51.

8. Jaggers JR, Sui X, Hooker SP, et al. Metabolic syndrome and risk of cancer mortality in men. Eur J Cancer. 2009;45(10):1831-1838.

9. Kanety H, Madjar Y, Dagan Y, et al. Serum insulin-like growth factor-binding protein-2 (IGFBP-2) is increased and IGFBP-3 is decreased in patients with prostate cancer: correlation with serum prostate-specific antigen. Journal of Clinical Endocrinology & Metabolism. July 1, 1993 1993;77(1):229-233.

10. Pollak M. Insulin, insulin-like growth factors and neoplasia. Best Pract Res Clin Endocrinol Metab. Aug 2008;22(4):625-638.

11. Sachdev D, Yee D. The IGF system and breast cancer. Endocr Relat Cancer. Sep 2001;8(3):197-209.

12. Cabin HS, Roberts WC. Relation of serum total cholesterol and triglyceride levels to the amount and extent of coronary arterial narrowing by atherosclerotic plaque in coronary heart disease. Quantitative analysis of 2,037 five mm segments of 160 major epicardial coronary arteries in 40 necropsy patients. The American journal of medicine. Aug 1982;73(2):227-234.

13. Freiberg JJ, Tybjærg-Hansen A, Jensen JS, Nordestgaard BG. Nonfasting Triglycerides and Risk of Ischemic Stroke in the General Population. JAMA: The Journal of the American Medical Association. November 12, 2008 2008;300(18):2142-2152.

14. Goodwin PJ, Boyd NF, Hanna W, et al. Elevated levels of plasma triglycerides are associated with histologically defined premenopausal breast cancer risk. Nutr Cancer. 1997;27(3):284-292.

15. Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. Journal of cardiovascular risk. Apr 1996;3(2):213-219.

16. Foekens JA, Schmitt M, van Putten WL, et al. Plasminogen activator inhibitor-1 and prognosis in primary breast cancer. Journal of Clinical Oncology. August 1, 1994 1994;12(8):1648-1658.

17. Landin K, Stigendal L, Eriksson E, et al. Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-1. Metabolism. 1990;39(10):1044-1048.

18. Alessi M-C, Juhan-Vague I. PAI-1 and the Metabolic Syndrome. Arteriosclerosis, Thrombosis, and Vascular Biology. October 1, 2006 2006;26(10):2200-2207.

19. Mertens I, Verrijken A, Michiels JJ, Van der Planken M, Ruige JB, Van Gaal LF. Among inflammation and coagulation markers, PAI-1 is a true component of the metabolic syndrome. Int J Obes. 2006;30(8):1308-1314.

20. Kuo HK, Yen CJ, Chang CH, Kuo CK, Chen JH, Sorond F. Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis. Lancet neurology. Jun 2005;4(6):371-380.

21. Pierce BL, Ballard-Barbash R, Bernstein L, et al. Elevated Biomarkers of Inflammation Are Associated With Reduced Survival Among Breast Cancer Patients. Journal of Clinical Oncology. July 20, 2009 2009;27(21):3437-3444.file:/content/27/21/3437.abstract

22. Forsythe C, Phinney S, Feinman R, et al. Limited Effect of Dietary Saturated Fat on Plasma Saturated Fat in the Context of a Low Carbohydrate Diet. Lipids. 2010;45(10):947-962.

23. Forsythe C, Phinney S, Fernandez M, et al. Comparison of Low Fat and Low Carbohydrate Diets on Circulating Fatty Acid Composition and Markers of Inflammation. Lipids. 2008;43(1):65-77.

24. Volek J, Phinney S, Forsythe C, et al. Carbohydrate Restriction has a More Favorable Impact on the Metabolic Syndrome than a Low Fat Diet. Lipids. 2009;44(4):297-309.

25. Brehm BJ, Seeley RJ, Daniels SR, D’Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab. Apr 2003;88(4):1617-1623.

26. Gardner CD, Kiazand A, Alhassan S, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. Jama. Mar 7 2007;297(9):969-977.

27. Hession M, Rolland C, Kulkarni U, Wise A, Broom J. Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. Obesity Reviews. 2009;10(1):36-50.

28. Hite AH, Berkowitz VG, Berkowitz K. Low-carbohydrate diet review: shifting the paradigm. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. Jun 2011;26(3):300-308.

29. Browning JD, Baker JA, Rogers T, Davis J, Satapati S, Burgess SC. Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. The American Journal of Clinical Nutrition. May 1, 2011 2011;93(5):1048-1052.

30. Feinman RD, Fine EJ. “A calorie is a calorie” violates the second law of thermodynamics. Nutr J. Jul 28 2004;3:9.

31. Fine EJ, Feinman RD. Thermodynamics of weight loss diets. Nutr Metab (Lond). Dec 8 2004;1(1):15.

32. Bautista-Castano I, Molina-Cabrillana J, Montoya-Alonso JA, Serra-Majem L. Variables predictive of adherence to diet and physical activity recommendations in the treatment of obesity and overweight, in a group of Spanish subjects. Int J Obes Relat Metab Disord. 2004;28(5):697-705.

33. Burke LE, Dunbar-Jacob J. Adherence to medication, diet, and activity recommendations: from assessment to maintenance. The Journal of cardiovascular nursing. 1995;9(2):62-79.

© 2015 CDR Health & Nutrition LLC. All Rights Reserved.


  1. Marci Daly

    In your point #8, you state that CRP is increased with the low-carb diet, however, in your discussion you talk about CRP increasing with the low-fat diet. Please clarify.


    1. cavemandoctor (Post author)

      Typo thanks! Fixed – I blame it on rushing to get this out at 6AM today!

      1. Tyler Wood

        I think #8 still needs to be updated?

      2. Tyler Wood

        Opps, disregard, I didn’t read it thru 🙂

        1. cavemandoctor (Post author)

          No prob!

  2. minie

    Caveman Doc,
    I was wondering if you will eventually be on TV e.g. ABC news maybe? I think you’re too good to be limited to the cyber world. Hoping to see you on tv on day. hehe

    1. cavemandoctor (Post author)

      Haha thanks! I wish, though I think I have a long way to go…

  3. Tom and Diane

    Rather than be on tv, do you publish papers? You have so much info that you can site references, just wondered if you went into more detail than your website?

    1. cavemandoctor (Post author)

      Hey Tom and Diane,

      I do, though more so on cancer and radiation, though I have 6 papers either under review or finishing up currently, so waiting on those. The entire process of submitting to acceptance to publishing takes a year at times. I had one on nutriton and cancer rejected recently, which is often the case with this kind of work – difficult to get accepted. I have an invited review that should be out soon that goes into much more detail.


      1. Tom and Diane

        Congrats of the various stages of all of your published papers! We’re familiar w/ the process, our son (a colleague of yours) and can appreciate all that is involved! We presume that your papers are like our son’s…not leisurely reading!
        Anyway, as a generality, do CRP levels fall w/ low carb diets? And rise w/ low fat diets?
        And good luck w/ the publishing!

      2. cavemandoctor (Post author)

        Thanks! I may actually be doing a paper with him soon on pretty boring physics and radiobiology haha.

        As for the CRP, so the long term studies (see the inflammation article I referred and articles by Volek and Forsyth, among others) and the long-term data for CRP, RBP4 (retinoid binding protein-4) and several other inflammatory factors paints quite a different picture. Plus, as you can read from the comment below, the CRP findings are less than ideal from a statistics point of view, though nothing new to headlines of these studies as they often find a way to trash low-carb diets.


  4. jake3_14

    A poster over at dove into the study data and posted this analysis of the CRP data.

    This CRP catastrophe it total hogwash. The CRP data shows that CRP fell in all three diets from 1.75 to 0.76 for low gI; to 0.78 for low fat; to 0.87 for LC. However, the study authors this about CRP:

    Variables with skewed distribution were log-transformed for analysis. One variable with extreme skew (CRP) was rank transformed for analysis.

    I dont know what rank transformed means, but it sounds like statistical gobbledy-gook. Extreme skew I think refers to the low fat data not being as “good” as the low GI. Maybe LC was compared to low GI, which was “better” than low fat for CRP? Or maybe the scatter of data points? But, anyway, the LC diet did not cause CRP to increase as was said in these stupid reports. It was cut in half.

    And Ludwig, who has been a bigtime anti-LCer for years, in his analysis admits that CRP “TENDED” to be higher. When he says tended, he means it wasn’t statistically significant. In other words, it is statistically the same as low fat and low GI.

    However, CRP tended to be higher with the very low-carbohydrate diet (median [95% CI], 0.78 [0.38-1.92] mg/L for low-fat diet; 0.76 [0.50-2.20] mg/L for low–glycemic index diet; and 0.87 [0.57-2.69] mg/L for very low-carbohydrate diet; P for trend by glycemic load = .05).

    The p for the trend by glycemic load (whatever that means) was .05, barely significant. But in the results table, the overall p for CRP was 0.13, nowhere near statistical significance.

    The whole tone of the article sounds apologetic, and I had to read it twice before I realized it was really pro-LC. Nice comments in it about LC and improvement in components of the metabolic syndrome. The CRP concern is totally made up, and the urinary cortisol excretion – who knows what that means, if it means anything. I’ve been reading about metabolism, inflammation, cardiac risk factors and diets for 10 years and I’ve never seen that referenced before. These guys like Ludwig and Bray will have to retire or die before any real progress will be made in sensible dietary advice.

    1. cavemandoctor (Post author)


      Easily the best comment ever posted on my site. I initially wasn’t even going to mention the CRP part because the stats were less than ideal, and then the second I got into work several people said to me “hey your diet causes an increase in CRP” and several emails poured in as well with similar headline. I decided to mention it briefly and thought the stats talk was possibly too much detail. SO, I thank you for your excellent description. Statistics are such a powerful tool, it is amazing how it can be used to make shoddy results acceptable (into JAMA no less).

      The apologetic tone is unbelievable and the response by Bray was no different (see here). I wrote a letter to the editor over Bray’s paper several months ago, which of course was rejected.

      In the words of the great Warburg (which he attributed to Max Planck) “science progresses not because scientists change their minds, but rather because scientists attached to erroneous views die, and are replaced”.

      Thanks for the great comments,

  5. Sheena

    Nice summary of a great article. Hopefully there will be more like it in the future, or at least looking more at the effects of macronutrients on weight-loss and inflammation-related diseases. One thing though, insulin sensitivity was lowest in the low-fat group, wasn’t it? Keep up the great work!

    1. cavemandoctor (Post author)

      Thanks Sheena!!! You are right and I fixed the typo. I really blame trying to crank this out at 6AM before work!

      And yes, hopefully this opens the door to future studies and further supports the potential empowerment a low-carb diet can give to those trying to lose weight.

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  8. Jodie


    I was wondering if you have any comment on the fact that although the JAMA article showed a difference in energy expenditure, it did not show a difference in weight. In fact, I’ve been searching the internet for studies and every time these various diets are compared isocalorically, the result seems to be that they total weight change does not differ. I think Low Carb is great and its been a benefit to me personally, but I would love to understand the chemistry a little better.

    Thanks for a great site!

    1. cavemandoctor (Post author)


      Thanks for the comments and thanks for reading. There is definitely some important information being withheld. Granted weight change wasn’t a primary outcome of the study, so reporting on it is slim.

      I would love to see a comparison of body-fat percentage changes between the diets, which was measured at baseline but conveniently left out. Partially to confirm my bias (that low-carb likely results in lower fat and higher muscle) but also because the data may give us some insight into the chemistry/physiology of what exactly is going on. Regardless, something is going on here and we are gaining at least some knowledge as to how our body responds to different foods beyond calories (and breaking down barriers in the diet and nutrition world). I don’t know of a lot of great studies, but there are some animal studies where we looked at ketogenic low-carb diets and we needed to feed mice 13% more calories just to keep weight – yes I know animal studies. A recent human one is here and here and yes, all the common dietary study criticisms apply.

      This was only a preliminary communication, so hopefully we can get some more data soon, but clearly the human body is more than just a calorie in and out metal box.


      1. Jodie

        Dear CD,

        Thanks for such a quick and thoughtful reply. Given the stakes here, its amazing that more isocaloric trials have not been done. Its seems to me that would be the best way to test the hypothesis. Here are links to two that I found. Both suggest that all the diets resulted in similar fat loss, but the LC showed definite benefits in the other measures of health:, and

        My personal believe (based on the numerous studies I have conducted using my own body as test subject) is that, regardless of the fat loss in isocaloric diets, LC is superior because it makes following a calorie restricted regimen so much easier. When I cut down the carbs and cut out the sugers, I’m not tormented by hunger and cravings. That alone is worth everything. The additional health benefits make the choice a relatively easy one for me. Now I just have to figure out how to get my family on board.

        Again, thank you for a wonderful blog and site!

        1. cavemandoctor (Post author)

          Hi Jodie,

          I have read these. The metabolic benefits have been shown in most if not all of the comparison studies. These are not metabolic ward studies, so all the typical issues exist. Check out the Bray article from JAMA too that I wrote about, showing that makeup of macro-nutrients effects fat and protein deposition. This and the study above show that calories clearly effect out body differently physiologically (which is why it is so much easier to follow. Hopefully many studies follow to answer these questions.


  9. Jodie

    Hi CD,

    Sorry to bombard you with questions but I’m really not sure where to go with this one. Is there any reason to avoid fried foods? I’m not talking about fried junk food at restaurants, but foods prepared at home? I can’t think of any, but we’ve been bombarded for years by the message that frying is killing us. What do you think?



    1. cavemandoctor (Post author)


      No problem. So I think the anti-frying was basically collateral damage of the anti-fat campaign. I have more issue with the breading… I think frying with stable, saturated compounds and never vegetable oils minimizes many of the issues with frying, but oxidation remains a concern. I pan fry a lot of my meats using saturated fats with high smoke points. Maybe not ideal but still my best attempt at eliminating oxidation.


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    “New JAMA Article Supports the Metabolic Advantage of Low-Carb Diets – Caveman Doctor” was
    indeed a excellent blog. If it included much more photographs this could be possibly even even
    better. All the best ,Christy

    1. cavemandoctor (Post author)

      Thanks! Pics and diagrams are always useful and I definitely need to do more, but they just take so much time…
      Take care,

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