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Original Research |

Effects of Low-Carbohydrate and Low-Fat Diets: A Randomized TrialEffects of Low-Carbohydrate and Low-Fat Diets

Lydia A. Bazzano, MD, PhD, MPH*; Tian Hu, MD, MS*; Kristi Reynolds, PhD; Lu Yao, MD, MS; Calynn Bunol, MS, RD, LDN; Yanxi Liu, MS; Chung-Shiuan Chen, MS; Michael J. Klag, MD, MPH; Paul K. Whelton, MD, MSc, MB; and Jiang He, MD, PhD
[+] Article and Author Information

* Drs. Bazzano and Hu contributed equally to this work.

From Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana; Kaiser Permanente Southern California, Pasadena, California; and Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Acknowledgment: The authors thank the study participants for their cooperation.

Grant Support: From the National Center for Research Resources of the National Institutes of Health (NIH/NCRR P20-RR017659) to the Tulane University Hypertension and Renal Center of Excellence.

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-0180.

Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Bazzano (e-mail, lbazzano@tulane.edu).

Requests for Single Reprints: Lydia Bazzano, MD, PhD, MPH, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street, SL-18, Suite 2000, New Orleans, LA 70112; e-mail, lbazzano@tulane.edu.

Current Author Ad dresses: Drs. Bazzano, Hu, Yao, Whelton, and He; Ms. Bunol; Ms. Liu; and Ms. Chen: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street, SL-18, Suite 2000, New Orleans, LA 70112.

Dr. Reynolds: Kaiser Permanente Southern California, 100 South Los Robles, 2nd Floor, Pasadena, CA 91101.

Dr. Klag: Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room W1041, Baltimore, MD 21205.

Author Contributions: Conception and design: L.A. Bazzano, T. Hu, K. Reynolds, L. Yao, M.J. Klag, J. He.

Analysis and interpretation of the data: L.A. Bazzano, T. Hu, Y. Liu, C.S. Chen, M.J. Klag, P.K. Whelton, J. He.

Drafting of the article: L.A. Bazzano, T. Hu.

Critical revision of the article for important intellectual content: L.A. Bazzano, T. Hu, K. Reynolds, L. Yao, P.K. Whelton, J. He.

Final approval of the article: L.A. Bazzano, K. Reynolds, M.J. Klag, P.K. Whelton, J. He.

Provision of study materials or patients: L.A. Bazzano, C. Bunol.

Statistical expertise: T. Hu, C.S. Chen.

Obtaining of funding: L.A. Bazzano.

Administrative, technical, or logistic support: L.A. Bazzano, L. Yao, C. Bunol.

Collection and assembly of data: L.A. Bazzano, L. Yao, C.S. Chen, J. He.

Ann Intern Med. 2014;161(5):309-318. doi:10.7326/M14-0180
Text Size: A A A

Background: Low-carbohydrate diets are popular for weight loss, but their cardiovascular effects have not been well-studied, particularly in diverse populations.

Objective: To examine the effects of a low-carbohydrate diet compared with a low-fat diet on body weight and cardiovascular risk factors.

Design: A randomized, parallel-group trial. (ClinicalTrials.gov: NCT00609271)

Setting: A large academic medical center.

Participants: 148 men and women without clinical cardiovascular disease and diabetes.

Intervention: A low-carbohydrate (<40 g/d) or low-fat (<30% of daily energy intake from total fat [<7% saturated fat]) diet. Both groups received dietary counseling at regular intervals throughout the trial.

Measurements: Data on weight, cardiovascular risk factors, and dietary composition were collected at 0, 3, 6, and 12 months.

Results: Sixty participants (82%) in the low-fat group and 59 (79%) in the low-carbohydrate group completed the intervention. At 12 months, participants on the low-carbohydrate diet had greater decreases in weight (mean difference in change, −3.5 kg [95% CI, −5.6 to −1.4 kg]; P = 0.002), fat mass (mean difference in change, −1.5% [CI, −2.6% to −0.4%]; P = 0.011), ratio of total–high-density lipoprotein (HDL) cholesterol (mean difference in change, −0.44 [CI, −0.71 to −0.16]; P = 0.002), and triglyceride level (mean difference in change, −0.16 mmol/L [−14.1 mg/dL] [CI, −0.31 to −0.01 mmol/L {−27.4 to −0.8 mg/dL}]; P = 0.038) and greater increases in HDL cholesterol level (mean difference in change, 0.18 mmol/L [7.0 mg/dL] [CI, 0.08 to 0.28 mmol/L {3.0 to 11.0 mg/dL}]; P < 0.001) than those on the low-fat diet.

Limitation: Lack of clinical cardiovascular disease end points.

Conclusion: The low-carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet. Restricting carbohydrate may be an option for persons seeking to lose weight and reduce cardiovascular risk factors.

Primary Funding Source: National Institutes of Health.


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Figure 1.

Study flow diagram.

* 5 participants in the low-fat group and 6 in the low-carbohydrate group had no data on body weight at randomization.

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Figure 2.

Predicted mean changes in body weight, fat mass, total–HDL cholesterol ratio, and triglyceride level in the low-fat and low-carbohydrate diet groups.

Results are from random-effects models and are expressed as means, with error bars representing 95% CIs. To convert triglyceride values to mg/dL, divide by 0.0113. HDL = high-density lipoprotein.

* P < 0.05 for between-group difference.

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Appendix Figure.

Predicted mean changes in lean mass, total cholesterol level, LDL cholesterol level, HDL cholesterol level, and 10-y Framingham risk score in the low-fat and low-carbohydrate diet groups.

Results are from random-effects models and are expressed as means, with error bars representing 95% CIs. To convert cholesterol values to mg/dL, divide by 0.0259. HDL = high-density lipoprotein; LDL = low-density lipoprotein.

* P < 0.05 for between-group difference.

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Good diet differentiation, but concern about unequal effort required
Posted on September 3, 2014
Christopher Gardner
Stanford University
Conflict of Interest: None Declared

Overall the study has several strengths and many similarities when compared to other Low-Fat vs. Low-Carb diet studies. Retention of 80% is good. Duration of 1-year is better than 3m or 6m but not as long as 2 years. NDS-R diet assessment repeatedly throughout the study is stronger than many studies, some of which did little to assess adherence. Diet adherence data suggest the two diets were clearly differentiated early in the study, and still clearly differentiated at 12 months - better than several studies where recidivism left little difference between diet groups by the end of the protocol. Sample size is reasonable - bigger than some, smaller than other studies.

Primary concern is with the goals of Low-Fat vs. Low-Carb. Authors state that, with no calorie restriction, main objective for Low-Fat was to achieve <30% energy from fat, and for Low-Carb <40 g carbohyrdates. With a baseline intake of ~35% fat, this means the Low-Fat group had the objective of reducing their fat % intake by 1/7th, a very modest change. In contrast, with a baseline mean intake of 242 grams of carbohydrate, the Low-Carb group objective was to cut this by 5/6ths, a hugely ambitious goal. Despite clearly differentiating the diets the two groups were on, this researcher considers it problematic that one group had a modest goal, leading to a modest weight change, while the other group had a wildly ambitious goal, and eventually achieved a larger weight loss.

Also of concern is that even with all the counseling described, and the provision of meal replacements once/day, the magnitude of weight loss among adults (mostly women) with a BMI of 30-45 kg/m^2 and baseline average weight just shy of 100 kg lost <2% vs. ~5% after a year of working at it.

Yes a 5% reduction in weight can lead to clinically meaningful improvements in risk factors, as was reported. But did we really need yet another study to point out that comparing a wildly ambitious diet with "usual care" (30% fat) could yield generally disappointing weight loss in both groups with a slight (and temporary?) reduction in risk factors?

What if the Low-Carb objective had been to drop from the baseline average (of both diets) of ~47% energy to <42% energy (modest goal), and the Low-Fat objective had been to drop from the baseline average (of both diets) of ~78 grams of fat/day to 1/6th of that, which would have been 13 grams of fat/day (ambitious goal).

Unequal effort demanded of participants on Low-Fat vs. Low-Carb brings comparison of these loosely defined terms into question, and with it the main conclusion of the paper.
What did participants really eat?
Posted on September 8, 2014
C. Murray Skeaff, Jim Mann, Lisa Te Morenga, Rachael McLean
University of Otago
Conflict of Interest: None Declared
Bazanno et al. hypothesised that participants following a diet low in carbohydrate would have lower body weight compared to those adhering to a diet low in fat; the results of their trial, they conclude, confirm this hypothesis (1). Neither diet included a specific calorie or energy intake goal, however, it appears that the behavioural curriculum followed by participants targeted weight loss because reported energy intakes declined from baseline during the intervention in both the low carbohydrate and low fat diet groups. Mean weight loss was greater amongst participants assigned to follow a diet low in carbohydrate. However, we estimate that underreporting of dietary energy intake was close to 50% in both groups during the intervention. Mean daily energy intakes at 3, 6, and 12 mo of the intervention were reported to be between 1258 and 1527 kcal. Energy intakes this low for a full year should have led to weight loss in excess of 30 kg rather than the 2 to 5 kg that occurred. The degree of under-reporting evident from these results makes it very difficult to know what participants actually ate and more importantly creates considerable uncertainty about the extent to which the greater weight loss in one diet group can be attributed to the macronutrient composition of the diet. This severe disconnection between reported and actual energy intake begs the question about the composition of the unreported and under-reported foods and suggests that forces other than the macronutrient composition of the diet may explain the weight differences. In this regard, the lack of blinding in weight loss trials makes it particularly difficult to disentangle the effect of macronutrients from the behaviours the diets may invoke. Katan remarked in an editorial several years ago (2) that participants in weight loss trials “may eat less not because of the protein or carbohydrate content of a diet but because of the diet’s reputation or novelty or because of the taste of particular foods in the diet.”. The widespread promotion of low carbohydrate diets may well explain these findings. A series of meta-analyses including one published recently (3) demonstrate little to differentiate long-term effects on body weight of various dietary patterns intended to achieve weight loss. The present study certainly does not refute this conclusion.

Murray Skeaff, Jim Mann, Lisa Te Morenga, and Rachael McLean

Department of Human Nutrition, University of Otago, New Zealand, no conflict of interest to declare.

1. Bazzano LA, Hu T, Reynolds K, Yao L, Bunol C, Liu Y, et al. Effects of Low-Carbohydrate and Low-Fat Diets. Ann Intern Med. 2014;161:309–18.
2. Katan MB. Weight-loss diets for the prevention and treatment of obesity. N Engl J Med. 2009;360:923–5.
3. Naude CE, Schoonees A, Senekal M, Young T, Garner P, Volmink J. Low Carbohydrate versus Isoenergetic Balanced Diets for Reducing Weight and Cardiovascular Risk: A Systematic Review and Meta-Analysis. PLoS ONE. 2014;9:e100652.

Importance of HDL increase in long-term cardiovascular effects of low-carbohydrate diet
Posted on September 9, 2014
Gaetano Santulli
Columbia University Medical Center - College of Physicians and Surgeons
Conflict of Interest: None Declared
To the Editor
In their randomized trial Bazzano, Hu and colleagues report that a low-carbohydrate diet is more effective for weight loss than a low-fat diet (1). Notably, such a difference was significant at 3- and 6-month follow up, but no longer obvious after 1 year (1). A similar pattern has been also evidenced in a recent meta-analysis (2). Of interest, the only parameters significantly different between the two diets at 12-month follow up were high-density lipoprotein (HDL) cholesterol level and 10-year Framingham risk score, which were remarkably not different at 3-month evaluation (1). Supporting this finding, the original Framingham Study unveiled that the risk for coronary artery disease increases sharply as HDL levels fall progressively below 40 mg/dL (3).
Equally important, approximately one third of the population enrolled in the trial was under a not better specified antihypertensive treatment (1). Given the complex relationship between endothelial dysfunction and HDL (4, 5), it would be noteworthy to know the results of the analysis distinguishing between hypertensive and non-hypertensive subjects, in order to explore new pathophysiological insights in the association linking hypertension and obesity.

1. Bazzano LA, Hu T, Reynolds K, Yao L, Bunol C, Liu Y, et al. Effects of low-carbohydrate and low-fat diets: a randomized trial. Ann Intern Med. 2014;161(5):309-18.
2. Nordmann AJ, Nordmann A, Briel M, Keller U, Yancy WS, Jr., Brehm BJ, et al. Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006;166(3):285-93.
3. Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA. 1986;256(20):2835-8.
4. Bonaa KH, Thelle DS. Association between blood pressure and serum lipids in a population. The Tromso Study. Circulation. 1991;83(4):1305-14.
5. Yuhanna IS, Zhu Y, Cox BE, Hahner LD, Osborne-Lawrence S, Lu P, et al. High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat Med. 2001;7(7):853-7.

Posted on September 12, 2014
Stephen F. Burns, Masashi Miyashita
Nanyang Technological University, Tokyo Gakugei University
Conflict of Interest: None Declared
Bazzano and colleagues provide confirmation of many recent studies that low-carbohydrate diets are at least as effective as low-fat diets for weight loss and can reduce some cardiovascular risk factors to a greater extent (1). However, an integral, early statement in the American Heart Association (AHA) dietary recommendations pertaining to weight loss is to incorporate a regular pattern of physical activity (2). It is well recognized that despite consuming high-carbohydrate diets endurance athletes have low concentrations of fasting and postprandial triglycerides (TG), high HDL-cholesterol levels and a lean body mass; factors which show little or no improvement with low-fat diets (1). From a public health standpoint, more compelling is an early randomized controlled trial in moderately overweight and obese males and females who followed a hypocaloric National Cholesterol Education Program (NCEP) Step I diet of 55% carbohydrate and 30% fat over 1 year (3). Males who walked or jogged an average of 2.1 km/day significantly lowered their TG by a further 0.36 mmol/L and increased their HDL-cholesterol by a further 0.12 mmol/L compared with those randomized to diet only. Moreover, they lost 3.5 kg more in fat mass and had a larger reduction in systolic blood pressure. The extent of these differences was not as great in women who walked or jogged an average of 1.8 km/day, but they were able to maintain their HDL-cholesterol levels over the year compared with a 0.15 mmol/L decrease in women who followed the diet only. Subsequent work from the same group in middle-aged individuals with high cholesterol showed that only a NCEP Step II diet in combination with walking or jogging ~16 km/wk over 1 year significantly reduced total and LDL-cholesterol and not the same diet or exercise alone (4). These interventions are supported by experimental data showing that when 60 minutes of daily brisk walking was added to a short-term, low-fat diet all increases in fasting and postprandial TG and TG-rich lipoproteins over a low-carbohydrate diet were obviated in postmenopausal women (5). Collectively, such evidence demonstrates the importance of physical activity in the AHA recommendations.

Bazzano and colleagues correctly suggest that restricting carbohydrate as an option for weight loss which helps reduce cardiovascular risk factors. We propose that if current AHA recommendations of reducing energy and fat intake and increasing physical activity are followed then the choice for individuals who wish to lose weight is widened but equally effective.

1. Bazzano LA, Hu T, Reynolds K, Yao L, Bunol C, Liu Y, et al. Effects of low-carbohydrate and low-fat diets: a randomized trial. Ann Intern Med. 2014; 161:309-18.
2. Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, et al. AHA Dietary Guidelines: revision 2000: A statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation. 2000; 102:2284-99.
3. Wood PD, Stefanick ML, Williams PT, Haskell WL. The effects on plasma lipoproteins of a prudent weight-reducing diet, with or without exercise, in overweight men and women. N Engl J Med. 1991; 325:461-6.
4. Stefanick ML, Mackey S, Sheehan M, Ellsworth N, Haskell WL, Wood PD. Effects of diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol. N Engl J Med. 1998; 339:12-20.
5. Koutsari C, Karpe F, Humphreys SM, Frayn KN, Hardman AE. Exercise prevents the accumulation of triglyceride-rich lipoproteins and their remnants seen when changing to a high-carbohydrate diet. Arterioscler Thromb Vasc Biol.
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Summary for Patients

Comparing Low-Fat and Low-Carbohydrate Diets

The full report is titled “Effects of Low-Carbohydrate and Low-Fat Diets. A Randomized Trial.” It is in the 2 September 2014 issue of Annals of Internal Medicine (volume 161, pages 309-318). The authors are L.A. Bazzano, T. Hu, K. Reynolds, L. Yao, C. Bunol, Y. Liu, C.S. Chen, M.J. Klag, P.K. Whelton, and J. He.


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