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A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity
Open accessAbstract
BACKGROUND: The effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed. METHODS: We randomly assigned 132 severely obese subjects (including 77 blacks and 23 women) with a mean body-mass index of 43 and a high prevalence of diabetes (39 percent) or the metabolic syndrome (43 percent) to a carbohydrate-restricted (low-carbohydrate) diet or a calorie- and fat-restricted (low-fat) diet. RESULTS: Seventy-nine subjects completed the six-month study. An analysis including all subjects, with the last observation carried forward for those who dropped out, showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet (mean [+/-SD], -5.8+/-8.6 kg vs. -1.9+/-4.2 kg; P=0.002) and had greater decreases in triglyceride levels (mean, -20+/-43 percent vs. -4+/-31 percent; P=0.001), irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications. Insulin sensitivity, measured only in subjects without diabetes, also improved more among subjects on the low-carbohydrate diet (6+/-9 percent vs. -3+/-8 percent, P=0.01). The amount of weight lost (P<0.001) and assignment to the low-carbohydrate diet (P=0.01) were independent predictors of improvement in triglyceride levels and insulin sensitivity. CONCLUSIONS: Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost. This finding should be interpreted with caution, given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study. Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed.
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“We did not confirm previous findings that low-carbohydrate or high-protein diets caused increased weight loss at 6 months3–12 and that the advantage of these diets usually eroded by 12 months, with weight loss that was nearly or fully equivalent to that with low-fat diets6,11,18 or other diets.12”
From Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates (2009) · cites this paper as [7]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Nevertheless, low-carbohydrate, high-fat diets may lead to spontaneous reduction in calorie reduction and increased weight loss, especially over the short term50–52.”
From Maintenance of Lost Weight and Long-Term Management of Obesity (2018) · cites this paper as [52]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Several trials showed that low-carbohydrate, high-protein diets resulted in more weight loss over the course of 3 to 6 months than conventional high-carbohydrate, low-fat diets,4–12 but other studies did not show this effect.13–17”
From Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates (2009) · cites this paper as [7]
In the citing paper
“Significant reductions in fat mass including truncal fat, which is a marker for visceral obesity, have been demonstrated in many studies [9,11,26,29].”
From The case for low carbohydrate diets in diabetes management (2005) · cites this paper as [11]
In the citing paper
“It is interesting that despite advocating ad libitum fat and protein intake, a LoCHO diet may be hypocaloric either by design or by spontaneous reduction of intake [8-12].”
From The case for low carbohydrate diets in diabetes management (2005) · cites this paper as [11]
In the citing paper
“There are several other reports indicating metabolic advantage in low carbohydrate diets over short term (3–6 months) [8,10,11,26-28].”
From The case for low carbohydrate diets in diabetes management (2005) · cites this paper as [11]
In the citing paper
“Conversely, LoCHO diets have been consistently demonstrated to lower triglycerides and increase HDL [8-11,26-28].”
From The case for low carbohydrate diets in diabetes management (2005) · cites this paper as [11]
In the citing paper
“LoCHO diets have been reported to reduce fat mass including truncal fat over long term in many studies [11,21,26,29].”
From The case for low carbohydrate diets in diabetes management (2005) · cites this paper as [11]
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BackgroundA high‐fibre bean‐rich diet versus a low‐carbohydrate diet for obesity
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Metabolic syndrome: dietary interventions
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“The high attrition rate was a limitation of this study, but is reported in most weight loss studies (29, 45, 46).”
ResultThe role of macronutrient content in the diet for weight management
Bray, G. A., & Siri-Tarino, P. W. (2016) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2016.04.009 · Cited by 47
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Semlitsch, T., Krenn, C., Jeitler, K., Berghold, A., Horvath, K., & Siebenhofer, A. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008274.pub4 · Cited by 47
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BackgroundResultLupin and soya reduce glycaemia acutely in type 2 diabetes
Dove, E. R., Mori, T. A., Chew, G. T., Barden, A. E., Woodman, R. J., Puddey, I. B., Sipsas, S., & Hodgson, J. M. (2011) · British Journal Of Nutrition · doi:10.1017/s0007114511001334 · Cited by 48
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“1%) compared to the previous studies [15,19], we could speculate that maintaining 4:1 ratio of ketogenic diet is rather a very harsh regimen to follow.”
ResultEffects of a low-carbohydrate diet on glycemic control in outpatients with severe type 2 diabetes
Haimoto, H., Sasakabe, T., Wakai, K., & Umegaki, H. (2009) · Nutrition & Metabolism · doi:10.1186/1743-7075-6-21 · Cited by 50
“The attrition rate for CRD was lower than that in other studies on CRDs (22% for 3 months, and 45%, 33% and 27% for 6 months) [7,12-14].”
ResultLow-carbohydrate versus balanced-carbohydrate diets for reducing weight and cardiovascular risk
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Insights on medical nutrition therapy for type 2 diabetes mellitus: an Indian perspective
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The role of high-protein diets in body weight management and health
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“ent finding in intervention studies has been a reduction in plasma triglyceride concentrations in conjunction with weight loss with moderately high-protein diets in comparison with high-carbohydrate diets((18,57,26,19,21,28,29,22,43)).”
Diabetes with obesity—Is there an ideal diet?
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Low‐Carbohydrate Diets and Risk of Incident Atrial Fibrillation: A Prospective Cohort Study
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“Interest in carbohydrate-restricted diets in the treatment of obesity has recently increased, because controlled clinical trials have demonstrated that carbohydrate-restricted diets are particularly effective in promoting weight loss in obese adults (1,2).”
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Varghese, A., Gusarov, I., Gamallo‐Lana, B., Dolgonos, D., Mankan, Y., Shamovsky, I., Phan, M., Jones, R., Gomez-Jenkins, M., White, E., et al. (2025) · Nature · doi:10.1038/s41586-025-08996-y · Cited by 52
Dietary Fat Increases Energy Intake Across the Range of Typical Consumption in the United States
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“Low carbohydrate diets have been reported to enhance weight loss in some studies (13-17) but not in others (19-21).”
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Mackerras, D. (2004) · Cited by 43
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Carbohydrate for weight and metabolic control: Where do we stand?
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“In particular, a very low-carbohydrate/high-fat diet (ketogenic diet, KD) is one of the most used dietary therapies for patients with diabetes or obesity in recent clinical studies [14–16].”
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Kinzig, K. P., Scott, K. A., Hyun, J., Bi, S., & Moran, T. H. (2005) · Obesity Research · doi:10.1038/oby.2005.205 · Cited by 42
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Diabesity in the Arabian Gulf: Challenges and Opportunities
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Induced Ketosis as a Treatment for Neuroprogressive Disorders: Food for Thought?
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The Relationship between Exercise, Nutrition and Type 2 Diabetes
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Different Criteria for Assessment of Roux-en-Y Gastric Bypass Success: Does Only Weight Matter?
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Low-Carbohydrate Diets: A Matter of Love or Hate
Frigolet, M.-E., Ramos Barragán, V.-E., & Tamez González, M. (2011) · Annals of Nutrition and Metabolism · doi:10.1159/000331994 · Cited by 47
The role of dietary carbohydrates in organismal aging
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Upper gastrointestinal function and glycemic control in diabetes mellitus
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More favorable dietary patterns are associated with lower glycemic load in older adults
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Supplementation with Soy-Protein−Rich Foods Does Not Enhance Weight Loss
St‐Onge, M., Claps, N., Wolper, C., & Heymsfield, S. B. (2007) · Journal of the American Dietetic Association · doi:10.1016/j.jada.2006.12.002 · Cited by 37
Diets for cardiovascular disease prevention: what is the evidence?
Walker, C., & Reamy, B. V. (2009) · PubMed · Cited by 37
The Carnivore Connection Hypothesis: Revisited
Brand-Miller, J. C., Griffin, H. J., & Colagiuri, S. (2011) · Journal of Obesity · doi:10.1155/2012/258624 · Cited by 39
“Studies have shown high-protein diets produce themost desirablemetabolic profile in individuals with type 2 diabetes [37–39].”
BackgroundJuraschek, S. P., McAdams‐DeMarco, M., Gelber, A. C., Sacks, F. M., Appel, L. J., White, K. J., & Miller, E. R. (2015) · Arthritis & Rheumatology · doi:10.1002/art.39527 · Cited by 37
Excess Weight Loss Variation in Late Postoperative Period of Gastric Bypass
Barhouch, A. S., Zardo, M., Padoin, A. V., de Paris, F. G. C., Casagrande, D. S., Chatkin, R., & Mottin, C. C. (2010) · Obesity Surgery · doi:10.1007/s11695-010-0202-3 · Cited by 36
“[17] and Foster et al.”
Amino acid‐dependent modulation of glucose metabolism in humans
Krebs, M. (2005) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2005.01506.x · Cited by 37
El Ghoch, M., Calugi, S., & Dalle Grave, R. (2016) · Nutrients · doi:10.3390/nu8070402 · Cited by 36
“, blood pressure, abdominal fat, triglyceridemia, High Density Lipoprotein (HDL) cholesterol, non-HDL cholesterol, fasting glucose, circulating insulin level, insulin sensitivity, HbA1c, and diabetes medication [17–23,25,29,31,34–39], their effect on psychosocial outcomes, in comparison to diets with other macronutrie…”
BackgroundLei, L., Huang, J., Zhang, L., Hong, Y., Hui, S., & Yang, J. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.935234 · Cited by 35
“Samaha, (32) American 6 Parallel 132 54 82.”
Low-Carbohydrate High-Fat Diet: A SWOC Analysis
Nuwaylati, D. A., Eldakhakhny, B. M., Bima, A. I. H., Sakr, H. F., & Elsamanoudy, A. Z. (2022) · Metabolites · doi:10.3390/metabo12111126 · Cited by 39
Wang, P., Tate, J. M., & Lloyd, S. G. (2008) · Life Sciences · doi:10.1016/j.lfs.2008.09.024 · Cited by 36
“Questions on LCD safety have focused on effects on circulating lipids; the limited studies have not found a detrimental effect on these, with a possible lowering of triglycerides (Foster et al., 2003; Samaha et al., 2003).”
BackgroundLifestyle Modification in the Management of Obesity
Wadden, T. A., McGuckin, B. G., Rothman, R. A., & Sargent, S. L. (2003) · Journal of Gastrointestinal Surgery · doi:10.1016/s1091-255x(03)00048-9 · Cited by 36
Rodríguez-Hernández, H., Morales-Amaya, U. A., Rosales-Valdéz, R., Rivera-Hinojosa, F., Rodríguez‐Morán, M., & Guerrero‐Romero, F. (2009) · British Journal Of Nutrition · doi:10.1017/s0007114509991231 · Cited by 39
“In this regard, some studies show that a low-carbohydrate diet promotes higher weight loss than low-fat diets (6,39) , but others highlight that a fat-restricted diet provides a high degree of satiety and promotes a higher reduction of body weight and better long-term adherence (40) .”
Palamara, K., Mogul, H. R., Peterson, S. J., & Frishman, W. H. (2006) · Cardiology in Review · doi:10.1097/01.crd.0000233903.57946.fd · Cited by 36
Low-carbohydrate diets, obesity, and metabolic risk factors for cardiovascular disease
Samaha, F. F., Foster, G. D., & Makris, A. (2007) · Current Atherosclerosis Reports · doi:10.1007/s11883-007-0059-7 · Cited by 35
“One study measured fasting glucose and insulin to derive the Quantitative Insulin Sensitivity Check Index (QUICKI) in participants without diabetes [ 9 ,10].”
BackgroundMethodResultInfluentialSelf-citationThe role of dietary protein in obesity
Magkos, F. (2020) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-020-09576-3 · Cited by 37
“Initial randomized trials published in the late 1990s and early 2000s clearly demonstrated that highprotein diets result in significantly more weight loss after 3– 6 months than conventional low-fat or high-carbohydrate diets [51, 52], but differences between diets are attenuated and not always significant after 1 yea…”
BackgroundRestoration of coronary endothelial function in obese Zucker rats by a low-carbohydrate diet
Focardi, M., Dick, G. M., Picchi, A., Zhang, C., & Chilian, W. M. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01202.2006 · Cited by 35
“A drastic reduction in carbohydrates also leads to an overall decrease in caloric intake (5); four randomized controlled clinical trials have compared low-carbohydrate diets with low-fat diets (6, 15, 50, 56, 69); all these studies found an average of 4- to 6-kg greater weight loss in the low-carbohydrate diet group a…”
BackgroundDietary Recommendations During and After Cancer Treatment: Consistently Inconsistent?
Champ, C. E., Mishra, M. V., Showalter, T. N., Ohri, N., Dicker, A. P., & Simone, N. L. (2013) · Nutrition and Cancer · doi:10.1080/01635581.2013.757629 · Cited by 34
Nutrition in patients with Type 2 diabetes: are low‐carbohydrate diets effective, safe or desirable?
Kennedy, R. L., Chokkalingam, K., & Farshchi, H. R. (2005) · Diabetic Medicine · doi:10.1111/j.1464-5491.2005.01594.x · Cited by 35
Treatment of Diabetes and Diabetic Complications With a Ketogenic Diet
Mobbs, C. V., Mastaitis, J. W., Isoda, F., & Poplawski, M. M. (2013) · Journal of Child Neurology · doi:10.1177/0883073813487596 · Cited by 38
“However, when surgery was performed on these mice (to allow monitoring of temperature by telemetry) and they lost weight as is usual after surgery, mice on the high-protein diet did exhibit higher levels of blood b-hydroxybutyric acid, consistent with the ketogenic effects of the high-protein, low-carbohydrate diet du…”
ResultInfluentialThe metabolic effects of low‐carbohydrate diets and incorporation into a biochemistry course
Pogozelski, W. K., Arpaia, N., & Priore, S. F. (2005) · Biochemistry and Molecular Biology Education · doi:10.1002/bmb.2005.494033022445 · Cited by 34
“A nearly universal result from studies of both ketogenic diets and nonketogenic lowcarbohydrate diets is that of lowered plasma triglyceride levels [51, 52, 54].”
BackgroundFiber, Protein, and Lupin-Enriched Foods: Role for Improving Cardiovascular Health
Belski, R. (2012) · Advances in food and nutrition research · doi:10.1016/b978-0-12-394597-6.00004-5 · Cited by 38
A Semiparametric Analysis of the Relationship of Body Mass Index to Mortality
Gronniger, J. T. (2005) · American Journal of Public Health · doi:10.2105/ajph.2004.045823 · Cited by 34
A Randomized Trial Comparing Low‐Fat and Low‐Carbohydrate Diets Matched for Energy and Protein
Segal-Isaacson, C. J., Johnson, S., Tomuta, V., Cowell, B., & Stein, D. T. (2004) · Obesity Research · doi:10.1038/oby.2004.278 · Cited by 35
Cost‐Effectiveness of a Low‐Carbohydrate Diet and a Standard Diet in Severe Obesity
Tsai, A. G., Glick, H. A., Shera, D., Stern, L., & Samaha, F. F. (2005) · Obesity Research · doi:10.1038/oby.2005.223 · Cited by 33
Self-citationNutrición y síndrome metabólico
Matía‐Martín, P., Pascual, E. L., & Pascual, A. L. C. (2007) · Revista Española de Salud Pública · doi:10.1590/s1135-57272007000500006 · Cited by 33
Shimizu, K., Saito, H., Sumi, K., Sakamoto, Y. S., Tachi, Y., & Iida, K. (2018) · Nutrition Research · doi:10.1016/j.nutres.2018.09.004 · Cited by 32
Hensrud, D. D. (2004) · Current Opinion in Gastroenterology · doi:10.1097/00001574-200403000-00012 · Cited by 33
Diet Modification for Treatment and Prevention of Obesity
Ness-Abramof, R., & Apovian, C. M. (2006) · Endocrine · doi:10.1385/endo:29:1:5 · Cited by 34
The burden of type 2 diabetes: strategies to prevent or delay onset.
Iqbal, N. (2007) · PubMed Central · Cited by 33
Self-citationWood, R. J., Gregory, S. M., Sawyer, J., Milch, C. M., Matthews, T. D., & Headley, S. A. E. (2012) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2011.0104 · Cited by 32
“…is a key component in the present study; several studies have assigned participants to either a LFD or CRD, yet dietary analyses revealed that the intended macronutrient distribution was not achieved, 24,25 making the results more applicable to dietary effectiveness than about dietary efficacy.”
Tsalissavrina, I., Wahono, D., & Handayani, D. (2013) · Jurnal Kedokteran Brawijaya · doi:10.21776/ub.jkb.2006.022.02.5 · Cited by 32
SCHUSDZIARRA, V., Hausmann, M., Wiedemann, C., Hess, J., Barth, C., Wagenpfeil, S., & Erdmann, J. (2010) · European Journal of Nutrition · doi:10.1007/s00394-010-0143-6 · Cited by 34
“While the data of acute weight loss are very intriguing [50, 51], a major shortcoming is the poor long-term adherence to the lowcarb concept [20, 79, 80] most likely due to the necessity of an approximately 10-fold reduction of habitual carbohydrate intake.”
BackgroundFat intake and the development of type 2 diabetes [Review]
Nagao, M., Asai, A., Sugihara, H., & Oikawa, S. (2015) · Endocrine Journal · doi:10.1507/endocrj.ej15-0055 · Cited by 34
ABO Genotype, ‘Blood-Type’ Diet and Cardiometabolic Risk Factors
Wang, J., García‐Bailo, B., Nielsen, D. E., & El‐Sohemy, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0084749 · Cited by 36
“40 of these lipids [118,119,120,121,122,123,124].”
Low-carbohydrate diets: An update on current research
Wylie‐Rosett, J., & Davis, N. J. (2009) · Current Diabetes Reports · doi:10.1007/s11892-009-0061-2 · Cited by 32
Metadata
- Authors
- Samaha, F. F., Iqbal, N., Seshadri, P., Chicano, K. L., Daily, D. A., McGrory, J., Williams, T., Williams, M., Gracely, E. J., & Stern, L.
- Affiliations
- Veterans Health Administration (US)
- University of Pennsylvania (US)
- Drexel University (US)
- ORCID
- Gracely, Edward J.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2003-05-22
- Volume
- 348
- Issue
- 21
- Pages
- 2074-2081
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2154184102
- Semantic Scholar
- b42feb4332c5988f5d769f116b2b96ffdfc37bd4
- Cited by
- 1,267
- References
- 20
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 26 · 2023: 24 · 2022: 39 · 2021: 38 · 2020: 58 · 2019: 33 · 2018: 36 · 2017: 36 · 2016: 43 · 2015: 28 · 2014: 37 · 2013: 46 · 2012: 62
- FWCI
- 70.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Keywords
- low-carbohydrate diet, low-fat diet, morbid obesity, weight loss, triglycerides, insulin sensitivity, diabetes mellitus, metabolic syndrome, atherosclerosis risk factors, dietary intervention
- MeSH terms
- Arteriosclerosis, Blood Glucose, Diabetes Mellitus, Diet, Reducing, Dietary Carbohydrates, Female, Humans, Insulin Resistance, Lipids, Male, Middle Aged, Obesity, Risk Factors, Triglycerides, Weight Loss, Body Mass Index, Diet, Fat-Restricted, Metabolic Syndrome
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