The full content of Annals is available to subscribers

Subscribe/Learn More  >
Original Research |

A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia: A Randomized, Controlled Trial

William S. Yancy Jr., MD, MHS; Maren K. Olsen, PhD; John R. Guyton, MD; Ronna P. Bakst, RD; and Eric C. Westman, MD, MHS
[+] Article, Author, and Disclosure Information

From the Center for Health Services Research in Primary Care, Department of Veterans Affairs Medical Center, and Duke University Medical Center, Durham, North Carolina.

Ann Intern Med. 2004;140(10):769-777. doi:10.7326/0003-4819-140-10-200405180-00006
Text Size: A A A

Over 24 weeks, a low-carbohydrate diet program led to greater weight loss, reduction in serum triglyceride level, and increase in HDL cholesterol level compared with a low-fat diet. These effects on weight loss and serum triglyceride level are similar to those in 4 randomized, controlled trials of the low-carbohydrate diet (710). The serum HDL cholesterol level also increased in 1 of these studies (9). The magnitude of weight loss that we observed compares favorably with that achieved with use of weight loss medications approved by the U.S. Food and Drug Administration, such as orlistat (decrease of about 9% at 6 months) (1819) and sibutramine (decrease of about 8% at 6 months) (20).

First Page Preview

View Large
First page PDF preview


Grahic Jump Location
Figure 1.
Flow of participants into the study.

LCKD = low-carbohydrate, ketogenic diet; LFD = low-fat, low-cholesterol, reduced-calorie diet.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Expected mean body weight over time, by diet group.

Expected mean body weight determined by linear mixed-effects model analysis. < 0.001 for linear and quadratic time-by-diet group interaction terms. LCKD = low-carbohydrate, ketogenic diet; LFD = low-fat, low-cholesterol, reduced-calorie diet.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Individual body weight trajectories, by diet group.

The orange line represents the observed trajectory for mean body weight in the low-fat, low-cholesterol, reduced-calorie diet (LCD) group (right) or the low-carbohydrate, ketogenic diet (LCKD) group (right). At week 24, the low-fat diet group included 33 rather than 34 participants because 1 participant contributed a blood specimen, but not weight measurements, at that time point.

Grahic Jump Location
Grahic Jump Location
Appendix Figure.
Reasons for discontinuation and individual weight trajectories for participants who dropped out, by diet group.

Top. Low-fat, low-cholesterol, reduced-calorie diet (LFD) group. Bottom. Low-carbohydrate, ketogenic diet (LCKD group). At week 24, the low-fat diet group included 33 rather than 34 participants because 1 participant contributed a blood specimen, but not weight measurements, at that time point. The dropout mean is the mean weight loss for each diet group's dropouts who were still in the study at that time point. The observed mean is the mean weight loss for each diet group's participants who were still in the study at that time point. The expected mean is the mean weight loss for each diet group's participants at that time point, by linear mixed-effects model analysis.

Grahic Jump Location




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).


Submit a Comment/Letter
Calorie intake with Low Carb group
Posted on May 21, 2004
thomas Mango
SUNY Stonybrook
Conflict of Interest: None Declared

Having lost 90 lbs using a low carbohydrate diet while counting calories as well, I noticed that my calorie count went down substantially while on a low carb diet. In fact without realizing it my calorie intake dropped significanly more than 500 to 1000 cals. Could the weight loss effect simply be from this effect combined with a satiety level obtained by eating more fat. PS It would be helpful if you qualified for the scientific community if the 20 gram carb restriction included fiber or if fiber was subtracted. I ask this because two cups of salad vegetables and one cup of acceptable vegetable is well under 20 grams if you subtract fiber.

Conflict of Interest:

None declared

Re: Calorie intake with Low Carb group
Posted on May 24, 2004
Michele E McAlister, M.S.,R.D.L.D.
Endocrinology Associates
Conflict of Interest: None Declared

I just have to wonder if the improvement in the triglycerides and HDL were as a result of the nutritional supplementation and less by the actual diet. We currently treat our patients with high triglycerides with omega 3 fish oil supplements. To really assess whether the effects were from the low carb diet or the nutritional supplementation, the low fat diet should be supplemented with the same supplements.

I also would like to know how the patients were monitored as far as if they were truly following the low fat diet. In working with patients for over 14 years I find that many people do not know how to translate the recommendations for 30% fat in to real people terms. They often mistakenly think they are to limit fat grams to 30 grams. Were they instructed to use more MUFA? I also would like to know if the patients were instructed to limit white flour products because that would also affect the triglyceride levels.

My last question is regarding to the method of analyzing fat loss versus muscle loss. How was this determined? My biggest concern is when people lose weight too fast they seem to lose more muscle mass which in turn slows the metabolism dowm.

Your consideration in this regard is certainly appreciated.

Conflict of Interest:

None declared

low carb low down
Posted on June 14, 2004
Maryam Fotouhinia
Medisys Health Group
Conflict of Interest: None Declared

The low carb diet may be more effective in rapid weight loss, however the improved triglycerides levels and the weight loss may be temporarily.

In this study, subjects in low carb group were given chromium picolinate which is compound that interacts with insulin and helps maintain regular blood sugar levels and it is commonly used for diabetic patients. Chromium which serves as an appetite suppressant was used only in the low carb group. Would the result have been as significant without such supplements?

Also as seen in my own practice as a dietitian, the low carb diets can not be maintained for extended periods of time. Generally the cravings for sweets and simple carbs are increased once the chromium is stoped and the allowed carbohydrate intake level is increased. Therefore the weight loss is temporarily and the triglycerides are also increased again depending on the level simple carbohydrate intake.

And finally, the increased HDL level, could it simply be due to higher cholesterol intake? Could the HDL be simply used to circulate the extra load of dietary cholesterol?

To determine the fate of low carb diets, all these and many other factors, some mentioned here some elsewhere, need to be evaluated in a different study and preferably one that is not funded by the Atkins foundation.

Low Carbohydrate Diet
Posted on August 13, 2004
Dean Ornish
University of California at San Francisco
Conflict of Interest: None Declared

Although purporting to show that a low-carbohydrate "˜Atkins' diet is more beneficial than a conventional "low-fat" AHA/NCEP diet, these two studies really documented that neither diet is very effective in lowering weight or LDL-cholesterol (LDL-C). In both studies, LDL-C did not change significantly and there were no significant differences in weight after one year (only about 3% weight loss), which was also seen in an earlier study.

The conventional AHA/NCEP "˜low-fat' diet is not very low in fat or cholesterol and reduces LDL-C by only 5% in most patients, if at all. Since this diet is often high in refined carbohydrates (which increase triglycerides), an Atkins diet often shows greater reductions in triglycerides, especially when taking fish oil.

In contrast, a diet containing 10% of calories from fat with little saturated fat and dietary cholesterol decreased LDL C by an average of 40% after one year in patients not taking lipid-lowering drugs. Also, they lost 24 pounds during the first year and kept off more than one-half of that weight five years later, whereas randomized control group patients on an AHA/NCEP diet did not lose weight. Exercise levels were not significantly different. It is important to distinguish between risk factors such as lipoproteins from direct measures of disease. Studies using serial coronary arteriography to assess patients consuming an AHA/NCEP diet revealed that the majority showed worsening of coronary atherosclerosis.4 In contrast, patients who followed a 10% fat unrefined foods diet demonstrated significant regression of coronary atherosclerosis after one year as measured by quantitative coronary arteriography and even more regression after five years.5 In addition, they had 2.5 times fewer cardiac events than randomized control group patients following an AHA/NCEP diet, who showed more progression of atherosclerosis after five years than after one year. There was a direct correlation between the intake of dietary cholesterol and total fat and changes in coronary atherosclerosis. Similar results were found by others. Also, 99% of experimental group patients stopped or reversed the progression of CHD as measured by cardiac PET scans.

Only one peer-reviewed study examined the effects of an Atkins diet on cardiovascular disease rather than only risk factors. Myocardial perfusion improved on a very low-fat whole foods diet but worsened on an Atkins diet. The burden of proof is on advocates of low carbohydrate diets to show otherwise in randomized controlled trials using direct measures of cardiovascular disease, not just risk factors or epidemiological studies, especially given data linking diets high in saturated fat and red meat with the incidence of heart disease, cancer, osteoporosis, and renal disease. The harmful effects of a high fat diet may be mediated through other mechanisms than traditional risk factors. For example, dietary fat intake increases plasma levels of factor VII coagulant activity (VIIc).4 Indeed, one man in the low-carbohydrate group developed angina and CAD near the end of the study even though his risk factors had improved,1 and another died of ischemic cardiomyopathy.2 We need to move beyond simplistic notions that anything which raises HDL-C is beneficial and anything that lowers HDL-C is harmful. Reducing dietary fat and cholesterol may cause a decrease in HDL-C because there is less need for it. There are no data showing that the physiologic reduction of HDL-C levels with a low fat diet is detrimental.

The debate should not be "˜low carbohydrate' versus "˜low fat.' Patients have a spectrum of dietary choices. To the degree they reduce their intake of refined carbohydrates and excessive fats and increase their intake of unrefined carbohydrates (fruits, vegetables, whole grains, legumes) and sufficient omega 3 fatty acids, they may feel better, lose weight, and gain health.

Dean Ornish, M.D. Preventive Medicine Research Institute Clinical Professor of Medicine, University of California, San Francisco

Yancy WS, Olsen MK, Guyton JR, Bakst RP, Westman EC. A low- carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia. Ann Intern Med. 2004; 140:769-777.

Stern L, Nayyar I, Seshadri P, Chicano KL, Daily DA, McGrory JM, et al. The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Ann Intern Med. 2004; 140:778-785.

Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS, et al. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med. 2003; 348:2082-90.

Ornish D. Concise Review: Intensive lifestyle changes in the management of coronary heart disease. In: Harrison s Principles of Internal Medicine (online), edited by Eugene Braunwald et al., 1999, and In: Braunwald E. Harrison s Advances in Cardiology. New York: McGraw Hill, 2002.

Ornish D, Scherwitz L, Billings J, et al. Intensive lifestyle changes for reversal of coronary heart disease Five-year follow-up of the Lifestyle Heart Trial. JAMA. 1998;280:2001-2007.

Ornish D. Was Dr. Atkins right? Journal of the American Dietetic Association. 2004;104(4):537-542.

Esselstyn CB Jr. Updating a 12-year experience with arrest and reversal therapy for coronary heart disease. Am J Cardiol. 1999 Aug 1;84(3):339-41, A8.

Gould KL, Ornish D, Scherwitz L, et al. Changes in myocardial perfusion abnormalities by positron emission tomography after long-term, intense risk factor modification. JAMA. 1995;274:894-901.

Fleming R, Boyd LB. The effect of high-protein diets on coronary blood flow. Angiology. 2000;51: 817-826.

Connor WE, Connor SL. The case for a low-fat, high-carbohydrate diet. N Engl J Med. 1997;337(8):562-563.

Conflict of Interest:

None declared

Is there a parasympathetic response to caloric restriction
Posted on November 12, 2004
Hospital Monte Naranco
Conflict of Interest: None Declared

Knowing that this response is a late response, I should like to pose a question to the authors. In both regimes the blood pressure and the heart rate diminishes. Can it be a parasympathetic effect?. If so, can it explain why the caloric restriction has no effect in the long term as it is compensated by a decreased energy expenditure?.

Thank you

Martín Caicoya

Conflict of Interest:

None declared

Submit a Comment/Letter

Summary for Patients

Effectiveness and Safety of Low-Carbohydrate Diets

The summary below is from the full report titled “A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia. A Randomized, Controlled Trial.” It is in the 18 May 2004 issue of Annals of Internal Medicine (volume 140, pages 769-777). The authors are W.S. Yancy Jr., M.K. Olsen, J.R. Guyton, R.P. Bakst, and E.C. Westman.


Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.


Buy Now for $32.00

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Related Articles
Related Point of Care
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.