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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The trial did not confirm earlier findings that low-carbohydrate or high-protein diets caused greater weight loss at six months and that this advantage eroded by twelve months.
“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]
The Weight Loss section reports significantly greater weight loss with the low-carbohydrate diet than with the low-fat diet at six months. The paper studied only six months and says it is unclear whether the benefits extend beyond that point; it cannot support the claim that the weight-loss advantage eroded by twelve months. (LLM, conf=0.90)
Experimental — accuracy not yet measuredLow-carbohydrate, high-fat diets may cause spontaneous reduction in calorie intake and increased weight loss, especially in the short term.
“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 measuredShort-term trials comparing low-carbohydrate, high-protein diets with conventional high-carbohydrate, low-fat diets have yielded inconsistent results.
“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]
Significant reductions in fat mass including truncal fat have been demonstrated in many studies with low carbohydrate diets.
“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]
Despite advocating ad libitum fat and protein intake, a LoCHO diet may be hypocaloric either by design or by spontaneous reduction of intake.
“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]
There are several other reports indicating metabolic advantage in low carbohydrate diets over the short term (3-6 months).
“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]
LoCHO diets consistently lower triglycerides and increase HDL.
“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]
LoCHO diets reduce fat mass including truncal fat over the long term in many studies.
“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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Similarity of the dog and human gut microbiomes in gene content and response to diet
Coelho, L. P., Kultima, J. R., Costea, P. I., Fournier, C., Pan, Y., Czarnecki-Maulden, G. L., Hayward, M. R., Forslund, S. K., Schmidt, T., Descombes, P., et al. (2018) · Microbiome · doi:10.1186/s40168-018-0450-3 · Cited by 362 · see citing works
“In humans, low-carbohydrate diets have been similarly effective at reducing weight, at least over the short term [24, 25], with evidence that they increase satiety compared to low-calorie diets [26].”
BackgroundKetone bodies: from enemy to friend and guardian angel
Kolb, H., Kempf, K., Röhling, M., Lenzen-Schulte, M., Schloot, N. C., & Martin, S. (2021) · BMC Medicine · doi:10.1186/s12916-021-02185-0 · Cited by 376 · see citing works
Behavioral Treatment of Obesity
Wadden, T. A., Crerand, C. E., & Brock, J. (2005) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2004.09.008 · Cited by 351 · see citing works
Risk Factors for the Metabolic Syndrome
Carnethon, M. R., Loria, C. M., Hill, J. O., Sidney, S. S., Savage, P. J., & Liu, K. (2004) · Diabetes Care · doi:10.2337/diacare.27.11.2707 · Cited by 343 · see citing works
Effects of Low-Carbohydrate and Low-Fat Diets: A Randomized Trial
Bazzano, L. A., Hu, T., Reynolds, K., Yao, L., Bunol, C., Liu, Y., Chen, C.-S., Klag, M. J., Whelton, P. K., & He, J. (2014) · Annals of Internal Medicine · doi:10.7326/m14-0180 · Cited by 346 · see citing works
The role of diet in the prevention of type 2 diabetes
Salas‐Salvadó, J., Martínez‐González, M. Á., Bulló, M., & Ros, E. (2011) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2011.03.009 · Cited by 341 · see citing works
PRIMARY PREVENTION OF DIABETES: What Can Be Done and How Much Can Be Prevented?
Schulze, M. B., & Hu, F. B. (2004) · Annual Review of Public Health · doi:10.1146/annurev.publhealth.26.021304.144532 · Cited by 330 · see citing works
Layman, D. K., Evans, E., Baum, J. I., Seyler, J., Erickson, D. J., & Boileau, R. A. (2005) · The Journal of Nutrition · doi:10.1093/jn/135.8.1903 · Cited by 330 · see citing works
“4 g/(kg d) result in increased weight loss (6–8,12), increased loss of body fat (7,8,10), attenuated loss of fat-free mass (FFM)(4) (6,8,10,13,14), improved glycemic control (6,10–12), improved blood lipid profiles (10,12,16,17), and enhanced satiety (15).”
BackgroundEffect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes
Hussain, T. A., Mathew, T. C., Dashti, A. A., Asfar, S., Al-Zaid, N., & Dashti, H. M. (2012) · Nutrition · doi:10.1016/j.nut.2012.01.016 · Cited by 329 · see citing works
“Furthermore, other investigators have reported that antidiabetic medications were decreased in some participants of the dietary program [19,21,22].”
BackgroundSeparate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia
Krauss, R. M., Blanche, P. J., Rawlings, R. S., Fernstrom, H. S., & Williams, P. T. (2006) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/83.5.1025 · Cited by 321 · see citing works
Snow, V. T., Barry, P. P., Fitterman, N., Qaseem, A., & Weiss, K. B. (2005) · Annals of Internal Medicine · doi:10.7326/0003-4819-142-7-200504050-00011 · Cited by 325 · see citing works
Das, S. K., Gilhooly, C. H., Golden, J. K., Pittas, A. G., Fuss, P. J., Cheatham, R. A., Tyler, S., Tsay, M., McCrory, M. A., Lichtenstein, A. H., et al. (2007) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/85.4.1023 · Cited by 314 · see citing works
Santos, F. L., Esteves, S. S., da Costa Pereira, A., Yancy Jr, W. S., & Nunes, J. P. L. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01021.x · Cited by 318 · see citing works
Austin, G. L., Ogden, L. G., & Hill, J. O. (2011) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.000141 · Cited by 317 · see citing works
I Diretriz Brasileira de Diagnóstico e Tratamento da Síndrome Metabólica
de Carvalho, M. H. C., Mancini, M. C., de Melo, M. E., Bahia, L., Negrão, C. E., de Matos, L. D. N. J., Sanjuliani, A. F., Kohlmann, O., Oliveira, J. E. P. D., Lerário, A. C., et al. (2005) · Arquivos Brasileiros de Cardiologia · doi:10.1590/s0066-782x2005000700001 · Cited by 300 · see citing works
Caprio, M., Infante, M., Moriconi, E., Armani, A., Fabbri, A., Mantovani, G., Mariani, S., Lubrano, C., Poggiogalle, E., Migliaccio, S., et al. (2019) · Journal of Endocrinological Investigation · doi:10.1007/s40618-019-01061-2 · Cited by 283 · see citing works
Lindström, J., Peltonen, M., Eriksson, J. G., Louheranta, A., Fogelholm, M., Uusitupa, M., & Tuomilehto, J. (2006) · Diabetologia · doi:10.1007/s00125-006-0198-3 · Cited by 293 · see citing works
Effects of a Low–Glycemic Load vs Low-Fat Diet in Obese Young Adults: A Randomized Trial
Ebbeling, C. B., Leidig, M. M., Feldman, H. A., Lovesky, M. M., & Ludwig, D. S. (2007) · JAMA · doi:10.1001/jama.297.19.2092 · Cited by 284 · see citing works
Higuchi, N., Kato, M., Shundo, Y., Tajiri, H., Tanaka, M., Yamashita, N., Kohjima, M., Kotoh, K., Nakamuta, M., Takayanagi, R., et al. (2008) · Hepatology Research · doi:10.1111/j.1872-034x.2008.00382.x · Cited by 285 · see citing works
Brinkworth, G. D., Noakes, M., Buckley, J. D., Keogh, J. B., & Clifton, P. M. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.27326 · Cited by 284 · see citing works
Novel Insights into the Pathogenesis and Management of the Metabolic Syndrome
Wang, H. H., Lee, D. K., Liu, M., Portincasa, P., & Wang, D. Q. ‐. (2020) · Pediatric Gastroenterology Hepatology & Nutrition · doi:10.5223/pghn.2020.23.3.189 · Cited by 294 · see citing works
“Clinical studies found that high daily carbohydrate intake is associated with increased plasma total cholesterol, LDL-cholesterol, and triglyceride concentrations, and reduced HDL-cholesterol levels [292,293,308-310].”
McAuley, K. A., Hopkins, C. M., Smith, K. J., McLay, R. T., Williams, S. M., Taylor, R. W., & Mann, J. I. (2005) · Diabetologia · doi:10.1007/s00125-004-1603-4 · Cited by 275 · see citing works
Klein, S., Sheard, N. F., Pi‐Sunyer, X., Daly, A. E., Wylie‐Rosett, J., Kulkarni, K. D., & Clark, N. G. (2004) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/80.2.257 · Cited by 275 · see citing works
Sainsbury, E., Kizirian, N. V., Partridge, S. R., Gill, T., Colagiuri, S., & Gibson, A. A. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.02.026 · Cited by 268 · see citing works
A low-carbohydrate, ketogenic diet to treat type 2 diabetes
Yancy, W. S., Foy, M. E., Chalecki, A. M., Vernon, M. C., & Westman, E. C. (2005) · Nutrition & Metabolism · doi:10.1186/1743-7075-2-34 · Cited by 270 · see citing works
“A few studies have shown that in non-diabetic individuals, low-carbohydrate diets were more effective than higher carbohydrate diets at improving fasting serum glucose [13,14] and insulin [6,14-16], and at improving insulin sensitivity as measured by the homeostasis model [6].”
InfluentialAccurso, A., Bernstein, R. K., Dahlqvist, A., Draznin, B., Feinman, R. D., Fine, E. J., Gleed, A., Jacobs, D. B., Larson, G., Lustig, R. H., et al. (2008) · Nutrition & Metabolism · doi:10.1186/1743-7075-5-9 · Cited by 263 · see citing works
“[27] are often cited as examples where low carbohydrate diets are more effective at 6 months but no better than low-fat diets at 1 year.”
BackgroundEfficacy of the Atkins diet as therapy for intractable epilepsy
Kossoff, E. H., Krauss, G. L., McGrogan, J. R., & Freeman, J. M. (2003) · Neurology · doi:10.1212/01.wnl.0000098889.35155.72 · Cited by 267 · see citing works
Saslow, L. R., Mason, A. E., Kim, S., Goldman, V., Ploutz-Snyder, R., Bayandorian, H., Daubenmier, J., Hecht, F. M., & Moskowitz, J. T. (2017) · Journal of Medical Internet Research · doi:10.2196/jmir.5806 · Cited by 265 · see citing works
“In previous trials of very low-carbohydrate diet programs in adults with type 2 diabetes that were at least 3 months or longer [7,38,43-58], researchers followed participants for a mean of 12 months.”
Schmidt, M., Pfetzer, N., Schwab, M., Strauss, I., & Kämmerer, U. (2011) · Nutrition & Metabolism · doi:10.1186/1743-7075-8-54 · Cited by 265 · see citing works
“Nowadays, the Atkins diet is very popular and although it’s longterm effect on weight loss is discussed controversially [23] undoubtedly it has a positive effect on the triglyceride and insulin levels [24,25] and no adverse side effects.”
BackgroundRandomized Clinical Trials of Weight Loss Maintenance: A Review
Turk, M. W., Yang, K., Hravnak, M., Sereika, S. M., Ewing, L. J., & Burke, L. E. (2009) · Journal of Cardiovascular Nursing · doi:10.1097/01.jcn.0000317471.58048.32 · Cited by 258 · see citing works
Carbohydrate intake and obesity
van Dam, R. M., & Seidell, J. C. (2007) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602939 · Cited by 261 · see citing works
“Table 2 shows the characteristics and results of five 12-month weight loss trials that randomized participants to very-low carbohydrate ‘Atkins’ type diets or low-fat diets (Foster et al., 2003; Samaha et al., 2003; Stern et al., 2004; Dansinger et al., 2005; McAuley et al., 2005, 2006; Gardner et al., 2007).”
BackgroundInfluentialKetosis and appetite-mediating nutrients and hormones after weight loss
Sumithran, P., Prendergast, L. A., Delbridge, E., Purcell, K., Shulkes, A., Kriketos, A. D., & Proietto, J. (2013) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2013.90 · Cited by 261 · see citing works
Expert panel report: Guidelines (2013) for the management of overweight and obesity in adults
(2014) · Obesity · doi:10.1002/oby.20660 · Cited by 257 · see citing works
Davis, N. J., Tomuta, N., Schechter, C., Isasi, C. R., Segal-Isaacson, C. J., Stein, D., Zonszein, J., & Wylie-Rosett, J. (2009) · Diabetes Care · doi:10.2337/dc08-2108 · Cited by 256 · see citing works
“Similar to prior studies, we observed a more rapid weight loss after initiation of a low-carbohydrate diet and equivalent weight loss after 1 year (2,3).”
ResultStamets, K., Taylor, D. S., Kunselman, A., Demers, L. M., Pelkman, C. L., & Legro, R. S. (2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2003.08.023 · Cited by 252 · see citing works
Lagiou, P., Sandin, S., Lof, M., Trichopoulos, D., Adami, H.-O., & Weiderpass, E. (2012) · BMJ · doi:10.1136/bmj.e4026 · Cited by 254 · see citing works
Naude, C. E., Schoonees, A., Senekal, M., Young, T., Garner, P., & Volmink, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100652 · Cited by 252 · see citing works
Low‐carbohydrate diets: nutritional and physiological aspects
Adam‐Perrot, A., Clifton, P. M., & Brouns, F. J. P. H. (2006) · Obesity Reviews · doi:10.1111/j.1467-789x.2006.00222.x · Cited by 249 · see citing works
“obesity reviews 7 , 49–58 consumption of low-CHO, high-fat diets, especially in diabetic subjects (6,12).”
BackgroundThe relation of saturated fatty acids with low-grade inflammation and cardiovascular disease
Ruiz-Núñez, B., Dijck-Brouwer, J., & Muskiet, F. A. J. (2016) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.12.007 · Cited by 246 · see citing works
South Asian diets and insulin resistance
Misra, A., Khurana, L., Isharwal, S., & Bhardwaj, S. (2008) · British Journal Of Nutrition · doi:10.1017/s0007114508073649 · Cited by 240 · see citing works
“(47) showed that severely obese subjects with a high prevalence of T2DM and the metabolic syndrome lost more weight and had greater improvements in the plasma TAG level and insulin sensitivity on a low-carbohydrate diet than those on a low-fat diet.”
BackgroundNutritional ketosis for weight management and reversal of metabolic syndrome
Gershuni, V. M., Yan, S. L., & Medici, V. (2018) · Current Nutrition Reports · doi:10.1007/s13668-018-0235-0 · Cited by 239 · see citing works
Wycherley, T. P., Noakes, M., Clifton, P. M., Cleanthous, X., Keogh, J. B., & Brinkworth, G. D. (2010) · Diabetes Care · doi:10.2337/dc09-1974 · Cited by 240 · see citing works
“The substitution of some dietary carbohydrate for protein in a low fat (<30% total energy) diet may improve body composition and CVD risk factors including insulin sensitivity, glycemic control and blood lipids in overweight/obese populations, including T2D(2-5).”
BackgroundThe Potential Health Benefits of the Ketogenic Diet: A Narrative Review
Dowis, K., & Banga, S. (2021) · Nutrients · doi:10.3390/nu13051654 · Cited by 243 · see citing works
“[61] also found that patients lost significantly more weight on a 30 g/carbohydrate per day diet for six months compared to a LFD.”
MethodNoto, H., Goto, A., Tsujimoto, T., & Noda, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055030 · Cited by 233 · see citing works
Heymsfield, S. B., Harp, J. B., Reitman, M. L., Beetsch, J. W., Schoeller, D. A., Erondu, N., & Pietrobelli, A. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/85.2.346 · Cited by 229 · see citing works
“Samaha et al (11) provided subjects weighing an average of 131.”
BackgroundInfluentialVolek, J. S., & Feinman, R. D. (2005) · Nutrition & Metabolism · doi:10.1186/1743-7075-2-31 · Cited by 223 · see citing works
“It is notable that Samaha et al studied a population in which 39 % had diabetes and 43% had MetS [46].”
MethodTherapeutic Potential of Ketone Bodies for Patients With Cardiovascular Disease
Yurista, S. R., Chong, C., Badimón, J. J., Kelly, D. P., de Boer, R. A., & Westenbrink, B. D. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.12.065 · Cited by 226 · see citing works
- 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 › Diet and metabolism studies
- Health Sciences › Medicine › Physiology › 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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