Objective: To examine changes in biomarkers of disease risk after 51 months of reduced energy intake and sustained weight loss.
Research Methods and Procedures: This study was conducted as a prospective, randomized, two-arm, parallel intervention for 12 weeks followed by a prospective, single-arm, 4-year trial in a university-based hospital clinic. One hundred patients were randomly assigned to one of two dietary interventions for 3 months. Group A was prescribed an energy-restricted diet of 1200 to 1500 kcal/d, and group B was prescribed an isocaloric diet, whereby two of three meals were replaced with nutrient-fortified liquid meal replacements. After 3 months, the patients were prescribed the same caloric reduction and used once-daily replacements for the succeeding 4 years. Body weight and blood pressure were checked monthly. Biomarkers of disease risk were measured after 3, 9, 15, 27, and 51 months.
Results: During the 3-month weight-loss period, body weight was reduced by 1.5 ± 0.4% and 7.8 ± 0.5% (mean ± SEM) for groups A and B, respectively. After 4 years, 75% of the patients were evaluated. Total mean weight loss was 3.3 ± 0.8% and 8.4 ± 0.8% for groups A and B, respectively. Both groups of patients showed significant improvement in glucose, insulin, triacylglycerol, and systolic blood pressure. Cholesterol concentrations were reduced in patients with high initial cholesterol levels and maintenance of a 7% weight loss.
Discussion: Providing a structured meal plan with liquid meal replacements is an effective treatment for obese subjects. Long-term maintenance of weight loss with meal replacements improves biomarkers of disease risk.
Obesity is a fast-growing worldwide epidemic (1). The health consequences of obesity include some of the most common diseases in our society: heart disease, diabetes, hypertension, joint disease, some common forms of cancer, and psychosocial morbidity. Recognition of the health consequences coupled with the increasing prevalence of obesity provide challenging evidence that the prevention and treatment of obesity is one of the most important health problems.
Clinical studies suggest that minimal, sustained weight loss of 5% to 10% can reduce or eliminate obesity-related disorders (2) (3) (4). Furthermore, a study from the American Cancer Society database demonstrated that among middle-aged obese women with no comorbid illnesses, intentional weight loss of >9 kg within the past year was associated with a 25% reduction in all-cause mortality over 12 years, including mortality caused by coronary heart disease (CHD) (5). From the same database, analysis of women with comorbid conditions (e.g., hypertension, CHD, diabetes, and stroke) with intentional weight loss had a 20% lower all-cause mortality, a 30% to 40% lower diabetes mortality, and a 10% lower CHD mortality (6).
Unfortunately, long-term outcome data show that most persons who lose weight regain the lost weight within 5 years (7), and that in those with abnormal biomarkers at the beginning of weight loss, these disease-associated risk factors are reestablished. However, more recent evidence indicates that dietary interventions that include the use of energy-controlled, nutrient-dense meal replacements were effective long-term (8) (9), and that patients who used nutritionally balanced prepackaged meals received nutritional completeness and showed better compliance than did those following a self-selected food plan (10) (11) (12).
This study was designed to test the hypothesis that liquid meal replacements given once or twice daily in addition to a low-fat diet can provide a sustained reduction in weight and that a 5% to 10% loss of body weight can cause a sustained improvement in disease-related biomarkers.
Research Methods and Procedures
For the purpose of the current report, patients were recruited from the Obesity Center of the University Hospital, where their physician for obesity management had referred them. All patients had been treated previously by the referring practitioner with energy-restricted diets for at least 3 months. Dissatisfaction with the degree of weight loss was the primary reason for transfer to the University Hospital.
The study was carried out according to the principles of the Helsinki Declaration, and the study protocol was approved by the Freiburg Ethics Committee International (Freiburg, Germany). Participants were informed that the purpose of the study during the first 3 months was to compare two different diet plans (one with conventional food and one with diet shakes) for the ability of the plans to promote weight loss, and that the purpose of the following 4 years was to evaluate a diet plan with integrated diet shakes for long-term weight maintenance and improvement of risk factors of disease.
Individuals with a history or presence of significant disease, endocrine disorder, psychiatric disease, alcohol or drug abuse, or abnormal laboratory tests of clinical significance were excluded. In addition, women were excluded if they were lactating, pregnant, or wished to become pregnant.
Patients were men and women 18 years of age and older whose body mass indexes (BMIs) were >25.0 and <40.0 kg/m2 and who indicated their willingness to be randomly assigned to study groups and to follow the protocol, which included monthly hospital visits for physical examinations and review of diaries. After giving informed consent, 100 patients entered the study.
The study design and primary outcomes were reported previously in detail (13). The study was a prospective dietary intervention trial. The study design was divided into phases. Phase 1 for weight loss was a 3-month randomized, parallel intervention trial in which patients were randomly assigned to one of two diet regimens each at 1200 to 1500 kcal/d. Phase 2 for weight maintenance followed phase 1 and consisted of a 4-year weight maintenance trial in which all patients were prescribed the same diet regimen with 1200 to 1500 kcal/d.
All patients were trained in behavior modification. They were instructed on food selection, meal portion control, and recording of daily dietary intakes using household measurements. Patients were informed on the importance of regular exercise and were encouraged to maintain their usual level of physical activity.
The dietary intervention was structured so that a staff nutritionist explained the diet plan in detail and counseled participants by using personalized sample menus and recipes. Throughout the study, patients were prescribed a low-calorie diet of regular foods providing 1200 to 1500 kcal/d and 19% to 21% of energy from protein, 48% to 54% of energy from carbohydrate, and 25% to 34% of energy from fat. Three meals (breakfast, lunch, and dinner) and two snacks (one between breakfast and lunch and one between lunch and dinner) were recommended.
Patients were randomly assigned to one of two dietary treatments (group A or B) by a computer-generated identification number. Group A was prescribed a low-calorie diet composed of regular foods and group B was prescribed the same diet but two meals daily were replaced with Slim-Fast shakes or soups (Slim-Fast Foods Co., West Palm Beach, FL). The third meal was low in fat and rich in vegetables, salads, and fruits and contained 600 to 900 kcal. Each meal replacement contained 200 to 220 kcal, 14.0 to 17.0 g of protein, 27.0 to 33.5 g of carbohydrate, 5.0 to 6.6 g of fat, and 4.5 to 6.5 g of fiber with vitamin and mineral fortification. Between meals, snacks of a vegetable, fruit, or Slim-Fast snack bar were recommended, providing 100 to 120 kcal. The nutritionist provided monthly personalized instructions by using food exchange lists and food diaries to equalize the prescribed energy intakes between groups A and B. Individual preferences for various food items were integrated into the diet plan.
During phase 2, the weight maintenance phase, all patients were instructed to replace one meal and one snack with energy-controlled, nutrient-dense meal and snack replacements. Each month, the food items recorded in the food diaries were checked and analyzed and dietary instructions reinforced, if needed.
Accurate daily recording of foods using household measurements was stressed, and daily food diaries were maintained for 7 consecutive days during the 2-week period before each visit. Records were reviewed with each patient and analyzed by the nutritionist. Nutrient calculations were carried out by using the German Food Code BLS and the Nutrilog program (GiV, Göttingen, Germany). During the entire study, monthly examinations were performed.
At each monthly visit, weight measurements to the nearest 0.1 kg were taken using the same precision scale (patients dressed only in underwear). At 8:00 am, blood pressure was measured to the nearest 5 mm Hg on the upper right arm using a mercury column manometer (patient in a supine position and rested for at least 10 minutes). At baseline, 3, 9, 15, 27, and 51 months, blood samples were taken at 8:00 am at least 10 hours after the previous meal. Biochemical measurements were performed by standard methods in the Department of Clinical Chemistry at the University Hospital.
Patients were analyzed according to their original assignment. Comparisons of values between the two groups were calculated by using a two-sample t test. Values are given as means ± SD, unless stated otherwise. For phase 1, a linear regression model was fit for percentage weight change and absolute body weight with sex and group as covariates. Generalized estimating equations (GEE) (14) were used to analyze phase 2 of the study. An unstructured, working correlation matrix was assumed for the GEE algorithm for all outcomes except percentage weight change, for which a compound symmetric structure was assumed. GEEs are a method of analyzing longitudinal data that do not rely on distributional assumptions. Furthermore, they give robust estimates of parameters and their SEs. For each outcome of interest, a GEE model was fit with group, time, and baseline outcome as main effects and all interactions between group and time. All outcomes were measured at 3, 9, 15, 27, and 51 months.
Twenty-five patients did not complete the trial. If these dropouts were informative, then regression estimates may have been biased. Because all patients completed phase 1 of the study, a linear regression model for percentage weight change at 3 months with group and dropouts (dropouts are defined as those who did not complete phase 2) as main effects was built. There was no significant difference in weight loss at 3 months between dropouts and those who completed both phases of the study. Because dropping out did not seem to depend on relative success or failure in phase 1 of the study, the phase 2 analyses were performed on an available case basis.
Fifty patients were randomly assigned to group A (control group) and 50 patients to group B (meal replacement group). Baseline characteristics of the 100 study patients showed no significant differences between the two groups in sex distribution, age, body weight, or BMI (Table 1).
Table 1. Clinical characteristics of subjects enrolled in the control group (A) and the meal replacement group (B)
Mean values ± SD.
Number of patients
41 women and 9 men
38 women and 12 men
46.5 ± 11.6
44.8 ± 9.7
Body weight (kg)
92.7 ± 9.8
92.6 ± 12.5
33.7 ± 4.0
33.1 ± 4.1
Energy and Cholesterol Intake
At baseline, reported energy intakes were 1797 ± 203 kcal/d and 1814 ± 84 kcal/d for groups A and B, respectively. At the end of phase 1, reported energy intakes were 1663 ± 86 kcal/d and 1375 ± 43 kcal/d, respectively. In both groups, energy intake had decreased after 3 months. In group B, the decrease was significant (p < 0.05). The difference in energy intake between the groups was also highly significant (p < 0.001). After 27 months, the reported energy intake in group A was reduced by 10.4% compared with baseline (p < 0.05). In group B, the reported energy intake after 27 months had increased but remained 13.1% below energy intake reported at baseline (p < 0.05).
The reported energy intake from fat was lowered from baseline to the end of the first 3 months by 19.1% and by 48.1% in groups A and B, respectively. After 27 months, the decrease of fat intake in group A was 29.6% from baseline. In group B, fat intake after 27 months had increased but remained 33.9% below the reported fat intake at baseline. The reported intake of cholesterol at baseline was 422 mg/d and 378 mg/d in groups A and B, respectively. After 3 months, cholesterol intake was reduced by 42.2% in group A (p < 0.05) and by 59.3% in group B (p < 0.05). After 27 months, in both groups, the reported cholesterol intake was below 200 mg/dL. Compared with baseline, in group A the reduction in cholesterol intake was 42.2% (p < 0.05) and in group B, 59.3% (p < 0.05; Table 2).
Table 2. Energy and cholesterol intake from self-reported 7-day diaries of obese subjects prescribed an energy restricted diet with conventional food (group A; n = 31) and with the meal replacement diet plan (group B; n = 32)
All 100 patients completed phase 1 of the study, and body weight loss was achieved in both groups after 3 months. In group A, weight was 1.3 ± 0.4 kg (means ± SEM) lower compared with baseline (p < 0.001), and in group B, weight was reduced by 7.1 ± 0.5 kg (p < 0.001). The difference was significant (p < 0.001) in all groups.
After phase 1, the weight-loss period, both groups experienced additional weight loss over the 4 years. In group A, body weight was reduced from 91.4 ± 11.6 kg to 88.6 ± 11.8 kg and in group B from 85.5 ± 13.4 kg to 83.1 ± 13.3 kg. There was a significant group effect in which group B had a greater change from baseline for all time-points. The difference in the initial weight loss observed at the completion of the first 3 months accounted for this significance (Figure 1).
Percentage Change in Weight and Biomarkers
Weight loss of 1.5 ± 0.4% and 7.8 ± 0.5% in groups A and B, respectively, was observed after the first 3 months. Only in group B were biomarkers of disease improved. After 51 months, compared with baseline, body weight in group A was reduced by 3.3 ± 0.8% and in group B by 8.4 ± 0.8%. Despite only modest weight loss of 3.3%, significant reductions of concentrations of glucose, insulin, and triglycerides were obtained. The weight loss of 8.4% in patients in group B was associated with more marked reductions of insulin and triglycerides. Although the concentrations of cholesterol were lowered during the trial in both groups of patients, the difference was not significant (Figure 2). However, there was a correlation for initial plasma cholesterol and percent decrease after 51 months, suggesting that those patients at higher risk experienced a greater benefit from weight loss and dietary change.
This prospective dietary intervention study of obese subjects demonstrates that the diet plan with liquid meal replacements resulted in greater weight loss than the self-selected diet composed of regular food. The result is highly significant, because all the study patients had been treated before with self-selected diet without having remarkable success, but using meal replacements coupled with low-fat food helped these patients to adhere to the diet regimen with subsequent weight loss. Similar results have been reported recently (15). The high rate of compliance with liquid meal replacements and prepackaged meals has also been shown in previous studies (8) (10) (11) (12). The greater compliance with diets that use meal replacements instead of self-selected food is believed to result from a more structured meal plan (16) (17), which reduces the number of decisions required for food choices and may help to prevent unintended dietary failures.
Most clinical studies dealing with diets using meal replacements or prepackaged meals are of short-term (up to 2 years). In this 4-year trial, it is shown that with this structured meal plan, obese individuals can follow a dietary food plan long-term. The results of this study suggest that the meal replacement strategy helps obese subjects lose weight and maintain weight loss. In addition, it helps to sustain healthy nutrition, while at the same time keeping fat intake low. Studies that examined the effect of weight loss on obesity-associated diseases showed that modest weight reduction produced significant improvements in the medical control of hypertension, diabetes, and dyslipidemias (3). Most studies that have shown a relationship between modest weight loss and improvement in biomarkers of disease risk are of relatively short duration (10) (18) (19). In fact, long-term studies suggest that the lipid-lowering effect of weight loss is not sustainable (20) (21) and that during weight maintenance, lipids may increase toward baseline levels (22). However, in this study, the reductions of triglycerides and cholesterol achieved during active weight loss were maintained during long-term weight maintenance. It is suggested that the altered nutrient profile of the weight-maintaining diet caused the sustained changes of blood lipids. The data from the dietary diaries showed that the energy derived from fat was maintained below 30% and that cholesterol intake was below 200 mg/d, meeting the lifestyle recommendations for patients at high risk for CHD (23). It must be considered that in individuals on conventional diets there is a tendency to underreport food intake (24) (25). Comparing the data of the dietary diaries with the weight loss, the patients in this study also may have reported less food than they actually consumed. However, the quality of food over time improved. The results suggest that a meal replacement strategy assists in initiating and sustaining healthy eating.
The American Diabetes Association guidelines for managing the diabetic patient recommend weight loss as a primary treatment modality (26), the Joint National Committee VI report encourages hypertensive patients with a BMI of 27 kg/m2 or greater to follow an energy-restricted diet (27), and the National Cholesterol Education Program lifestyle recommendations for treating hypercholesterolemia imply that the daily caloric intake should be modified to induce weight loss in overweight subjects (23). To gain the medical benefits of weight reduction, the target of weight loss should be 5% to 10% of initial body weight (2). This amount of desirable weight loss is a reasonably attainable goal for most overweight and obese people. The addition of meal replacements integrated to an energy-restricted diet plan can improve compliance to the dietary regimen and help obese subjects to achieve significant weight loss and to maintain the weight loss.
We thank the Slim-Fast Foods Company for providing the diet shakes and nutrition bars for use in this study. We thank Katja Huber (research laboratory of the Department of Medicine, University of Ulm, Ulm, Germany) for her technical assistance. We thank Hank Frier (Slim-Fast Foods Company, West Palm Beach, FL) for fruitful discussions and assistance in preparing the manuscript.