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Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet
Open accessAbstract
BACKGROUND: Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates. METHODS: In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non-restricted-calorie. RESULTS: The rate of adherence to a study diet was 95.4% at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05 for all comparisons among treatment groups). The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat, protein, and cholesterol and had the highest percentage of participants with detectable urinary ketones (P<0.05 for all comparisons among treatment groups). The mean weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean-diet group, and 4.7 kg for the low-carbohydrate group (P<0.001 for the interaction between diet group and time); among the 272 participants who completed the intervention, the mean weight losses were 3.3 kg, 4.6 kg, and 5.5 kg, respectively. The relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol was 20% in the low-carbohydrate group and 12% in the low-fat group (P=0.01). Among the 36 subjects with diabetes, changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low-fat diet (P<0.001 for the interaction among diabetes and Mediterranean diet and time with respect to fasting glucose levels). CONCLUSIONS: Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions. (ClinicalTrials.gov number, NCT00160108.)
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“In addition, trials of low-carbohydrate diets have reported a very low incidence of urinary ketosis after 6 months,6,8,12 suggesting that in most overweight people, it is futile to sustain a low intake of carbohydrates.”
From Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates (2009) · cites this paper as [12]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe cited source doesn’t support the claim as written.
In the citing paper
“The most important feature for diet modification is a reduced-calorie meal plan, which is essential for effective weight loss.687–690”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [690]
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In the citing paper
“Intensive lifestyle intervention resulted in 1-year weight loss of 8.6%, and 4-year weight loss of 4.7% compared with 1.1% in the standard group, and was accompanied by lower A1C with less need for DM medications, DM remission in ~10% of persons, lower diastolic and systolic BP, improved lipids (higher HDL-C, lower triglycerides), improvements in OSA as reflected by lower apnea hypopnea index sc”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [690]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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 [12]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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 [12]
Experimental — accuracy not yet measured
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In the citing paper
“The mean differences among the groups in fat, carbohydrate, or protein intake at 6 months were nevertheless often greater than those in several previous trials comparing diets for weight loss.11,12,19,21,26”
From Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates (2009) · cites this paper as [12]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Several recent trials have also shown that continued contact with participants after weight loss is associated with less regain.12,24,37,38”
From Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates (2009) · cites this paper as [12]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Intensive lifestyle intervention resulted in 1-year weight loss of 8.6%, and 4-year weight loss of 4.7% compared with 1.1% in the standard group, and was accompanied by lower A1C with less need for DM medications, DM remission in ~10% of persons, lower diastolic and systolic BP, improved lipids (higher HDL-C, lower triglycerides), improvements in OSA as reflected by lower apnea hypopnea index sc”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [690]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Clinical trials have demonstrated the efficacy of lifestyle programs that include behavioral interventions and have underscored particular practices that are most likely to be associated with success.690,811”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [690]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Structured lifestyle interventions that include reduced-calorie low-fat diets in persons with overweight or obesity have been shown to prevent progression from prediabetes to DM,690,811,827 and to lower A1C, BP, and triglycerides in persons with T2D.678,690,702–704,927,928”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [690]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The 0.9% absolute (12% relative) HbA1c reduction observed at 2 years is consistent with low carbohydrate studies reporting HbA1c reductions of 8–15% at 2 to 3.5 years (52, 55–57) with medication reduction.”
From Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial (2019) · cites this paper as [52]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“They tend to be relatively high in unsaturated fat, particularly from extravirgin olive oil.”
From Popular dietary patterns: alignment with American Heart Association 2021 dietary guidance: a scientific statement from the American Heart Association. (2023) · cites this paper as [20]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“studies comparing dietary composition (e.g., variations in protein content, carbohydrate restriction, or glycemic index) have generally demonstrated modest effects on weight maintenance, with differences between diets attenuating over time, particularly beyond one year”
From Weight maintenance after discontinuation of GLP-1 therapies (2026) · cites this paper as [63]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A1C was lowest in the lowcarbohydrate group after 2 years”
From Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report (2019) · cites this paper as [90]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“fasting plasma glucose was lower in the Mediterranean-style group than in the lower-fat group (90).”
From Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report (2019) · cites this paper as [90]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Only two trials have reported dietary intake beyond 1 year,12,26 and one of them provided foods to the participants.12”
From Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates (2009) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“Other studies showed increased weight loss at 1 to 2 years with diets that were high in unsaturated fat12,21,26 or with low-fat, high-carbohydrate vegetarian diets.22,24”
From Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates (2009) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“Other interventions using carbohydrate restriction reported variable long-term glycemic improvement outcomes (52–57).”
The cited source says what the claim attributes to it.
In the citing paper
“The Mediterranean-style pattern has demonstrated a mixed effect on A1C, weight, and lipids in a number of RCTs (85 -90).”
From Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report (2019) · cites this paper as [90]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The principal outcome measure in Look AHEAD was CVD events, and the study was discontinued prematurely when an interim analysis showed no difference between treatment groups after 9.6 years median follow-up.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [690]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“For example, persons who self-monitor and record weight, food intake, or physical activity are more likely to achieve weight management goals.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [690]
Experimental — accuracy not yet measuredIn the citing paper
“Weight-loss trials1–3 have typically enrolled obese or overweight persons who attempted substantial short-term weight loss on specialized diets, thus limiting the generalizability of the findings to nonobese populations and to the factors that determine long-term, gradual weight gain.”
From Changes in diet and lifestyle and long-term weight gain in women and men (2011) · cites this paper as [2]
In the citing paper
“Strategies such as the MD and the DASH diet appear to be more sustainable [77] in the long term and have fewer gastrointestinal side effects that often lead to malnutrition.”
From Nutrition and Physical Activity in Optimizing Weight Loss and Lean Mass Preservation in the Incretin-Based Medications Era: A Narrative Review (2025) · cites this paper as [77]
In the citing paper
“The DIRECT trial (Dietary Intervention Randomized Controlled Trial), in which participants received prepared meals to enhance adherence, reported greater weight loss with an ad libitum low-carbohydrate diet than with a calorie-restricted low-fat diet, which persisted at 2 y (158).”
From The carbohydrate-insulin model: A physiological perspective on the obesity pandemic (2021) · cites this paper as [158]
In the citing paper
“Our results with regard to body weight are consistent with those of other trials (23, 24) and a recent meta-analysis (25).”
From Effects of Low-Carbohydrate and Low-Fat Diets: A Randomized Trial (2014) · cites this paper as [23]
In the citing paper
“Previous studies have examined the effects of low-carbohydrate diets on CVD risk factors, but most of these trials had small sample sizes or low completion rates, did not assess a typical low-carbohydrate diet for weight loss, or did not include diverse populations (19–24).”
From Effects of Low-Carbohydrate and Low-Fat Diets: A Randomized Trial (2014) · cites this paper as [23]
In the citing paper
“Other intervention trials using the Mediterranean diet have also shown some beneficial effects in the treatment of obesity, the metabolic syndrome, and arthritis (28–30).”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [28]
In the citing paper
“High dietary salt consumption was estimated to be responsible for 102 000 annual deaths”
From Heart Disease and Stroke Statistics—2013 Update: A Report From the American Heart Association (2013) · cites this paper as [110]
In the citing paper
“low dietary omega-3 fatty acids for 84 000 annual deaths”
From Heart Disease and Stroke Statistics—2013 Update: A Report From the American Heart Association (2013) · cites this paper as [110]
In the citing paper
“and low consumption of fruits and vegetables for 55 000 annual deaths.110”
From Heart Disease and Stroke Statistics—2013 Update: A Report From the American Heart Association (2013) · cites this paper as [110]
In the citing paper
“high dietary trans fatty acids for 82 000 annual deaths”
From Heart Disease and Stroke Statistics—2013 Update: A Report From the American Heart Association (2013) · cites this paper as [110]
In the citing paper
“However, RCTs designed to investigate weight loss and having equal-intensity interventions in each dietary arm have demonstrated that macronutrient composition has little independent effect on weight loss.169–172”
From Components of a Cardioprotective Diet: New Insights (2011) · cites this paper as [171]
In the citing paper
“Adherence to any weight loss diet, regardless of its macronutrient composition, was the best determinant of success.169–172”
From Components of a Cardioprotective Diet: New Insights (2011) · cites this paper as [171]
In the citing paper
“and the higher palatability and acceptance of MeDiets in comparison with low-fat diets 17,18 lend support to our hypothesis.”
From Cohort Profile: Design and methods of the PREDIMED study (2012) · cites this paper as [17]
In the citing paper
“In the DIRECT trial, subjects in the KD group started with carbohydrate intake of 20 g/day and ended at 12 months with 40% of TEI from carbohydrate intake [68].”
From Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials (2023) · cites this paper as [68]
In the citing paper
“Results from the Dietary Intervention Randomized Controlled Trial (DIRECT) assigning obese adults with T2DM to a calorie-restricted Mediterranean-style, a calorie-restricted lower-fat, or a low carbohydrate eating pattern (28% of calories from carbohydrate), showed that HbA1c was lowest in the low carbohydrate group after 2 years, whereas fasting plasma glucose was lower in the Mediterranean-style”
From Effects of diet, lifestyle, Chrononutrition and alternative dietary interventions on postprandial Glycemia and insulin resistance (2022) · cites this paper as [105]
In the citing paper
“Also, the reduction in insulin levels and other measures of IR, i.e., the homeostatic model assessment (HOMA) index, triggered by this dietary approach, are precocious and sustainable over time [17,18].”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [17]
In the citing paper
“The Mediterranean diet (MedDiet), characterized by high consumption of extra-virgin olive oil (EVOO), nuts, red wine, vegetables and other polyphenol-rich elements, has proved to be associated with greater improvement of IR in obese individuals, when compared to other nutritional interventions.”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [17]
In the citing paper
“These glyco-metabolic benefits appear to be sustainable over time, independent of body weight change, as they do not occur with other successful nutritional interventions for weight loss [17].”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [17]
In the citing paper
“Monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), in forms of olive oil, nuts and seeds in plant-based dietary regimens, may function as the driving force for the amelioration of glucose metabolism, insulin sensitivity, blood lipids and CVD risk, observed either in diabetic individuals [17,40,41] or in the general population [42].”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [17]
In the citing paper
“In particular, important health benefits have been demonstrated for the Mediterranean eating pattern, which can considerably improve fasting glucose, glycated hemoglobin (HbA1c) and insulin levels in obese diabetic patients, when compared to low-fat diets [17].”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [17]
In the citing paper
“Instead, previous studies have focused on comparing low-carb to low-fat eating patterns (3–10).”
In the citing paper
“Low-carbohydrate patterns generally refer to patterns with total carbohydrate targets between 20% and 40% of kilocalaroies.20,[29][30][31][32][33][34][35][36]”
From Popular dietary patterns: alignment with American Heart Association 2021 dietary guidance: a scientific statement from the American Heart Association. (2023) · cites this paper as [20]
In the citing paper
“Low-fat patterns generally target total fat intake between 20% and 30% of kilocalories alongside other healthy dietary guidelines.20,[29][30][31][32][33][34][35][36]”
From Popular dietary patterns: alignment with American Heart Association 2021 dietary guidance: a scientific statement from the American Heart Association. (2023) · cites this paper as [20]
In the citing paper
“Multiple RCTs including people with type 2 diabetes have reported that a Mediterranean eating pattern (120,203-208) can improve both glycemic management and blood lipids.”
From 5. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes:Standards of Care in Diabetes—2023 (2023) · cites this paper as [204]
In the citing paper
“longer-term studies (52 weeks) showed mixed effects on A1C in adults with type 2 diabetes (82–85), and results were confounded by pharmacologic weight loss therapy.”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [85]
In the citing paper
“In a 2-year dietary intervention study, Mediterranean and low-carbohydrate diets were found to be effective and safe alternatives to a low-fat diet for weight reduction in moderately obese participants (85).”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [85]
In the citing paper
“Although significant reductions in triglycerides occurred after 2 months on the Atkins and Zone diets, these effects were no longer significant after 12 months.”
From Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association (2011) · cites this paper as [440]
In the citing paper
“Weight loss was similar after 12 months (4.8 to 7.3 kg) for all 4 diets.”
From Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association (2011) · cites this paper as [440]
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Metadata
- Authors
- Shai, I., Schwarzfuchs, D., Henkin, Y., Shahar, D. R., Witkow, S., Greenberg, I., Golan, R., Fraser, D., Bolotin, A., Vardi, H., Tangi-Rozental, O., Zuk-Ramot, R., Sarusi, B., Brickner, D., Schwartz, Z., Sheiner, E., Marko, R., Katorza, E., Thiery, J., Fiedler, G. M., Blüher, M., Stumvoll, M., & Stampfer, M. J.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Shimon Peres Negev Nuclear Research Center (IL)
- Soroka Medical Center (IL)
- University Hospital Leipzig (DE)
- Leipzig University (DE)
- Harvard University (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2008-07-17
- Volume
- 359
- Issue
- 3
- Pages
- 229-241
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2146463166
- Semantic Scholar
- 77344a3328e9620b32871d25bb734173c95c6354
- Cited by
- 2,143
- References
- 43
- Citations by year
- 2026: 54 · 2025: 68 · 2024: 79 · 2023: 119 · 2022: 126 · 2021: 125 · 2020: 191 · 2019: 115 · 2018: 123 · 2017: 112 · 2016: 115 · 2015: 106 · 2014: 121 · 2013: 136 · 2012: 127
- FWCI
- 95.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- IRIS eCampus Telematic University (Università degli Studi eCampus) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Keywords
- weight loss, Mediterranean diet, low-carbohydrate diet, low-fat diet, obesity, dietary adherence, dietary fiber, urinary ketones, TC/HDL-C ratio, glycemic control, fasting blood glucose, insulin, type 2 diabetes, dietary intervention
- MeSH terms
- Blood Glucose, Energy Intake, Female, Follow-Up Studies, Glycated Hemoglobin, Humans, Ketones, Lipids, Male, Middle Aged, Obesity, Surveys and Questionnaires, Biomarkers, Weight Loss, Body Mass Index, Diet, Fat-Restricted, Diet, Mediterranean, Diet, Carbohydrate-Restricted
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