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. The dramatic increase in obesity worldwide remains challenging and underscores the urgent need to test the effectiveness and safety of several widely used weight-loss diets. Low-carbohydrate, high-protein, high-fat diets (referred to as low-carbohydrate diets) have been compared with low-fat, energy-restricted diets. A meta-analysis of five trials with 447 participants and a recent 1-year trial involving 311 obese women suggested that a low-carbohydrate diet is a feasible alternative to a low-fat diet for producing weight loss and may have favorable metabolic effects.
However, longer-term studies are lacking. A Mediterranean diet with a moderate amount of fat and a high proportion of monounsaturated fat provides cardiovascular benefits. A recent review citing several trials included a few that suggested that the Mediterranean diet was beneficial for weight loss. However, this positive effect has not been conclusively demonstrated. Common limitations of dietary trials include high attrition rates (15 to 50% within a year), small size, short duration, lack of assessment of adherence, and unequal intensity of intervention.
We conducted the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT) to compare the effectiveness and safety of three nutritional protocols: a low-fat, restricted-calorie diet; a Mediterranean, restricted-calorie diet; and a low-carbohydrate, non–restricted-calorie diet. Eligibility and Study Design We conducted the trial between July 2005 and June 2007 in Dimona, Israel, in a workplace at a research center with an on-site medical clinic. Recruitment began in December 2004. The criteria for eligibility were an age of 40 to 65 years and a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of at least 27, or the presence of type 2 diabetes (according to the American Diabetes Association criteria ) or coronary heart disease, regardless of age and BMI.
Persons were excluded if they were pregnant or lactating, had a serum creatinine level of 2 mg per deciliter (177 μmol per liter) or more, had liver dysfunction (an increase by a factor of at least 2 above the upper limit of normal in alanine aminotransferase and aspartate aminotransferase levels), had gastrointestinal problems that would prevent them from following any of the test diets, had active cancer, or were participating in another diet trial. The participants were randomly assigned within strata of sex, age (below or above the median), BMI (below or above the median), history of coronary heart disease (yes or no), history of type 2 diabetes (yes or no), and current use of statins (none. Nutritional and Color Labeling of Food in the Cafeteria Lunch is typically the main meal in Israel. The self-service cafeteria in the workplace provided a varied menu and was the exclusive source of lunch for the participants. A dietitian worked closely with the kitchen staff to adjust specific food items to specific diet groups.
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.
Each food item was provided with a label showing the number of calories and the number of grams of carbohydrates, fat, and saturated fat, according to an analysis based on the Israeli nutritional database. Each food item was also labeled with a full circle (indicating “feel free to consume”) or a half circle (indicating “consume in moderation”). The labels were color-coded according to diet group and were updated daily (see ). Electronic Questionnaires at Baseline and Follow-up Adherence to the diets was evaluated by a validated food-frequency questionnaire that included 127 food items and three portion-size pictures for 17 items.
A subgroup of participants completed two repeated 24-hour dietary recalls to verify absolute intake (data not shown). We used a validated questionnaire to assess physical activity. At baseline and at 6, 12, and 24 months of follow-up, the questionnaires were self-administered electronically through the workplace intranet. The 15% of participants who requested aid in completing the questionnaires were assisted by the study nurse. The electronic questionnaire helped to ensure completeness of the data by prompting the participant when a question was not answered, and it permitted rapid automated reporting by the group dietitians. Outcomes The participants were weighed without shoes to the nearest 0.1 kg every month.
With the use of a wall-mounted stadiometer, height was measured to the nearest millimeter at baseline for determination of BMI. Waist circumference was measured halfway between the last rib and the iliac crest. Blood pressure was measured every 3 months with the use of an automated system (Datascop Acutor 4) after 5 minutes of rest. Blood samples were obtained by venipuncture at 8 a.m. After a 12-hour fast at baseline and at 6, 12, and 24 months and were stored at –80°C until an assay for lipids, inflammatory biomarkers, and insulin could be performed.
Levels of fasting plasma glucose, glycated hemoglobin, and liver enzymes were measured in fresh samples. The level of glycated hemoglobin was determined with the use of Cobas Integra reagents and equipment. Serum levels of total cholesterol, high-density-lipoprotein (HDL) cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides were determined enzymatically with a Wako R-30 automatic analyzer, with coefficients of variation of 1.3% for cholesterol and 2.1% for triglycerides. Plasma insulin levels were measured with the use of an enzyme immunometric assay (Immulite automated analyzer, Diagnostic Products), with a coefficient of variation of 2.5%. Plasma levels of high-molecular-weight adiponectin were measured by an enzyme-linked immunosorbent assay (ELISA) (AdipoGen or Axxora), with a coefficient of variation of 4.8%. Plasma leptin levels were assessed by ELISA (Mediagnost), with a coefficient of variation of 2.4%. Plasma levels of high-sensitivity C-reactive protein were measured by ELISA (DiaMed), with a coefficient of variation of 1.9%.
The clinic and laboratory staff members were unaware of the treatment assignments, and the study coordinators were unaware of all outcome data until the end of the intervention. Statistical Analysis For weight loss, the prespecified primary aim was the change in weight from baseline to 24 months. We used the Israeli food database in the analysis of the results of the dietary questionnaires.
We analyzed the dietary-composition data and biomarkers with the use of raw unadjusted means, without imputation of missing data. We compared the dietary-intake values between groups at each time point with the use of an analysis of variance in which all pairwise comparisons among the three diet groups were performed with the use of Tukey's Studentized range test. We transformed physical-activity scores into metabolic equivalents per week according to the amount of time spent in various forms of exercise per week, with each activity weighted in terms of its level of intensity. For intention-to-treat analyses, we included all 322 participants and used the most recent values for weight and blood pressure.
To evaluate the repeated measurements over time, we used generalized estimating equations for panel data analysis, also known as cross-sectional time-series analysis, with the use of the Stata software XTGEE command; this allowed us to account for the nonindependence of repeated measurements of the same bioindicator in the same participant over time. We used age, sex, time point, and diet group as explanatory variables in our models. To study changes over time and the effects of sex or the presence or absence of diabetes, we added appropriate interaction terms.
We assessed the within-person changes from baseline in each diet group with the use of pairwise comparisons. We calculated the homeostasis model assessment of insulin resistance (HOMA-IR) according to the following equation: insulin (U/ml) × fasting glucose (mmol/liter) ÷ 22.5. For a mean (±SD) difference between groups of at least 2±10 kg of weight loss, with 100 participants per group and a type I error of 5%, the power to detect significant differences in weight loss is greater than 90%. We used SPSS software, version 15, and Stata software, version 9, for the statistical analysis.
Characteristics of the Participants The baseline characteristics of the participants are shown in Table 1 Baseline Characteristics of the Study Population.. The mean age was 52 years and the mean BMI was 31. Most participants (86%) were men. The overall rate of adherence ( Figure 1 Enrollment of the Participants and Completion of the Study.
) was 95.4% at 12 months and 84.6% at 24 months; the 24-month adherence rates were 90.4% in the low-fat group, 85.3% in the Mediterranean-diet group, and 78.0% in the low-carbohydrate group (P=0.04 for the comparison among diet groups). During the study, there was little change in usage of medications, and there were no significant differences among groups in the amount of change; four participants initiated and three stopped cholesterol-lowering therapy.
Twenty participants initiated blood-pressure treatment, five initiated medications for glycemic control, and one reduced the dosage of medications for glycemic control. Dietary Intake, Energy Expenditure, and Urinary Ketones At baseline, there were no significant differences in the composition of the diets consumed by participants assigned to the low-fat, Mediterranean, and low-carbohydrate diets.
Download Michael 4 Base Daz 3d. Daily energy intake, as assessed by the food-frequency questionnaire, decreased significantly at 6, 12, and 24 months in all diet groups as compared with baseline (P. Weight Loss A phase of maximum weight loss occurred from 1 to 6 months and a maintenance phase from 7 to 24 months.
All groups lost weight, but the reductions were greater in the low-carbohydrate and the Mediterranean-diet groups (P. Lipid Profiles Changes in lipid profiles during the weight-loss and maintenance phases are shown in Figure 3 Changes in Cholesterol and Triglyceride Biomarkers According to Diet Group during the Maximum Weight-Loss Phase (1 to 6 Months) and the Weight-Loss Maintenance Phase (7 to 24 Months) of the 2-Year Intervention. Panel A shows the results for serum high-density lipoprotein (HDL) cholesterol, Panel B for serum triglycerides, Panel C for serum low-density lipoprotein (LDL) cholesterol, and Panel D for the ratio of total cholesterol to HDL cholesterol. Vertical bars indicate standard deviations. To statistically evaluate the changes in weight measurements over time, generalized estimating equations were used, with the low-fat group as the reference group. The explanatory variables were age, sex, time point, and diet group.
Results are presented for the 82% of the study population (263 participants) with blood-sample data at all time points (90 in the low-fat group, 92 in the Mediterranean-diet group, and 81 in the low-carbohydrate group). The P values for the comparison between the low-fat group and the Mediterranean-diet group are 0.94 for HDL cholesterol, 0.21 for triglycerides, 0.41 for LDL cholesterol, and 0.23 for the ratio of total cholesterol to HDL cholesterol. The P values for the comparison between the low-fat group and the low-carbohydrate group are 0.01 for HDL cholesterol, 0.03 for triglycerides, 0.94 for LDL cholesterol, and 0.01 for the ratio of total cholesterol to HDL cholesterol. To convert values for cholesterol to millimoles per liter, multiply by 0.02586. To convert values for triglycerides to millimoles per liter, multiply by 0.01129.. HDL cholesterol ( ) increased during the weight-loss and maintenance phases in all groups, with the greatest increase in the low-carbohydrate group (8.4 mg per deciliter [0.22 mmol per liter], P. High-Sensitivity C-Reactive Protein, High-Molecular-Weight Adiponectin, and Leptin The level of high-sensitivity C-reactive protein decreased significantly (P.
Fasting Plasma Glucose, HOMA-IR, and Glycated Hemoglobin Among the 36 participants with diabetes ( ), only those in the Mediterranean-diet group had a decrease in fasting plasma glucose levels (32.8 mg per deciliter); this change was significantly different from the increase in plasma glucose levels among participants with diabetes in the low-fat group (P. Discussion In this 2-year dietary-intervention study, we found that the Mediterranean and low-carbohydrate diets are effective alternatives to the low-fat diet for weight loss and appear to be just as safe as the low-fat diet.
In addition to producing weight loss in this moderately obese group of participants, the low-carbohydrate and Mediterranean diets had some beneficial metabolic effects, a result suggesting that these dietary strategies might be considered in clinical practice and that diets might be individualized according to personal preferences and metabolic needs. The similar caloric deficit achieved in all diet groups suggests that a low-carbohydrate, non–restricted-calorie diet may be optimal for those who will not follow a restricted-calorie dietary regimen. The increasing improvement in levels of some biomarkers over time up to the 24-month point, despite the achievement of maximum weight loss by 6 months, suggests that a diet with a healthful composition has benefits beyond weight reduction. The present study has several limitations. We enrolled few women; however, we observed a significant interaction between the effects of diet group and sex on weight loss (women tended to lose more weight on the Mediterranean diet), and this difference between men and women was also reflected in the changes in leptin levels.
This possible sex-specific difference should be explored in further studies. The data from the few participants with diabetes are of interest, but we recognize that measurement of HOMA-IR is not an optimal method to assess insulin resistance among persons with diabetes. We relied on self-reported dietary intake, but we validated the dietary assessment in two different dietary-assessment tools and used electronic questionnaires to minimize the amount of missing data. Finally, one might argue that the unique nature of the workplace in this study, which permitted a closely monitored dietary intervention for a period of 2 years, makes it difficult to generalize the results to other free-living populations.
However, we believe that similar strategies to maintain adherence could be applied elsewhere. The strengths of the study include the one-phase design, in which all participants started simultaneously; the relatively long duration of the study; the large study-group size; and the high rate of adherence. The monthly measurements of weight permitted a better understanding of the weight-loss trajectory than was the case in previous studies. We observed two phases of weight change: initial weight loss and weight maintenance.
The maximum weight reduction was achieved during the first 6 months; this period was followed by the maintenance phase of partial rebound and a plateau. Among all diet groups, weight loss was greater for those who completed the 24-month study than for those who did not. Even moderate weight loss has health benefits, and our findings suggest benefits of behavioral approaches that yield weight losses similar to those obtained with pharmacotherapy. We distinguished between changes in levels of biomarkers (leptin, adiponectin, and high-sensitivity C-reactive protein) that are apparently related to loss of adipose tissue and changes in biomarkers (triglycerides, HDL cholesterol, glucose, and insulin) that apparently reflect, in part, the effects of specific diet composition. The changes we observed in levels of adiponectin and leptin, which were consistent in all groups, reflect loss of weight.
Consumption of monounsaturated fats is thought to improve insulin sensitivity, an effect that may explain the favorable effect of the Mediterranean diet on glucose and insulin levels. The results imply that dietary composition modifies metabolic biomarkers in addition to leading to weight loss. Our results suggest that health care professionals might consider more than one dietary approach, according to individual preferences and metabolic needs, as long as the effort is sustained.
This trial also suggests a model that might be applied more broadly in the workplace. As Okie recently suggested, using the employer as a health coach could be a cost-effective way to improve health. The model of intervention with the use of dietary group sessions, spousal support, food labels, and monthly weighing in the workplace within the framework of a health promotion campaign might yield weight reduction and long-term health benefits.
Supported by the Nuclear Research Center Negev (NRCN), the Dr. And Veronica Atkins Research Foundation, and the S. Daniel Abraham International Center for Health and Nutrition, Ben-Gurion University, Israel.
No potential conflict of interest relevant to this article was reported. This article (10.1056/NEJMoa0708681) was updated on December 30, 2009, at NEJM.org.
We thank the 322 participants in the Dietary Intervention Randomized Controlled Trial (DIRECT) for their consistent cooperation, as well as the consultants and health care providers (Yitzhak Gurevitz, Hassia Krakauer, Meir Yoseffi, Meyer Aviv, Ilanit Asulin, Zvi Zur, Sapir Medikar, Haim Strasler, Avraham Shlonsky, Dr. Abby Bloch, and Dr.
Ayala Canfi), the workplace cafeteria managers (Naftali Tal, Yitzchak Chen, Yair Tubul, and the Norcate Company), the adviser researchers (Drs. Ofra Paz-Tal, Assaf Rudich, Amir Tirosh, Ilana Harman-Bohem, and Ronit Andvelt), and the members of the DIRECT steering committee (Prof. Shimon Weitzman, Prof. Uri Goldbourt, and Prof. Eran Leitersdorf) for their invaluable contributions. Source Information From the S. References • 1 Obesity: preventing and managing the global epidemic: report of a WHO consultation.
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