Effect of 6-Month Adherence to a Very Low Carbohydrate Diet Program Eric C. Westman, MD, MHS, William S. Yancy, MD, Joel S. Edman, DSc, Keith F. Tomlin, Christine E. Perkins, MSW PURPOSE: To determine the effect of a 6-month very low carbohydrate diet program on body weight and other metabolic parameters. SUBJECTS AND METHODS: Fifty-one overweight or obese healthy volunteers who wanted to lose weight were placed on a very low carbohydrate diet (⬍25 g/d), with no limit on caloric intake. They also received nutritional supplementation and recommendations about exercise, and attended group meetings at a research clinic. The outcomes were body weight, body mass index, percentage of body fat (estimated by skinfold thickness), serum chemistry and lipid values, 24-hour urine measurements, and subjective adverse effects. RESULTS: Forty-one (80%) of the 51 subjects attended visits through 6 months. In these subjects, the mean (⫾ SD) body weight decreased 10.3% ⫾ 5.9% (P ⬍0.001) from baseline to 6 months (body weight reduction of 9.0 ⫾ 5.3 kg and body mass index reduction of 3.2 ⫾ 1.9 kg/m2). The mean percentage of body weight that was fat decreased 2.9% ⫾ 3.2% from baseline to 6 months (P ⬍0.001). The mean serum bicarbonate level decreased 2 ⫾ 2.4 mmol/L (P ⬍0.001) and blood urea nitrogen level increased 2 ⫾ 4 mg/dL (P ⬍0.001). Serum total cholesterol level decreased 11 ⫾ 26 mg/dL (P ⫽ 0.006), low-density lipoprotein cholesterol level decreased 10 ⫾ 25 mg/dL (P ⫽ 0.01), triglyceride level decreased 56 ⫾ 45 mg/dL (P ⬍0.001), high-density lipoprotein (HDL) cholesterol level increased 10 ⫾ 8 mg/dL (P ⬍0.001), and the cholesterol/HDL cholesterol ratio decreased 0.9 ⫾ 0.6 units (P ⬍0.001). There were no serious adverse effects, but the possibility of adverse effects in the 10 subjects who did not adhere to the program cannot be eliminated. CONCLUSION: A very low carbohydrate diet program led to sustained weight loss during a 6-month period. Further controlled research is warranted. Am J Med. 2002;113:30 –36. ©2002 by Excerpta Medica, Inc. O during a 6-week period in 2 studies (7,8). Two previous studies, involving a total of 30 subjects, have shown that a very low carbohydrate diet can lead to weight loss during an 8-week period (9,10). Because the research regarding very low carbohydrate diets is limited by small sample sizes and short treatment duration, the potential risks and benefits of this dietary approach need further investigation. The purpose of this study was to assess the effect of a very low carbohydrate diet program on body weight and other parameters during a 6-month period. besity has been implicated as the second leading preventable cause of death in the United States, and prospective studies suggest that intentional weight loss leads to a decrease in mortality (1,2). Fewer than 20% of those attempting to lose weight follow the mostly widely recommended combination of eating fewer calories and exercising at least 150 minutes per week (3). There has recently been a resurgence of diets promoting low carbohydrate intake, but the scientific evidence supporting the safety and effectiveness of these diets is limited. Several short-term laboratory studies have demonstrated that very low carbohydrate diets (carbohydrate intake ⬍25 g/d) can have substantial effects on metabolism, including weight loss and ketonemia (4). The magnitude of ketonemia, which is similar to that observed after fasting but lower than that in diabetic ketoacidosis (5,6), was not associated with adverse effects From the Division of General Internal Medicine (ECW, WSY, KFT, CEP), Duke University, Durham, North Carolina; the Ambulatory Care Service (ECW, WSY), Durham Veterans Affairs Medical Center, Durham, North Carolina; and the Center for Integrative Medicine (JSE), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. This study was funded by an unrestricted grant from the Atkins Center for Complementary Medicine, New York, New York. Requests for reprints should be addressed to Eric C. Westman, MD, MHS, Division of General Internal Medicine, Suite 200-B Wing, 2200 West Main Street, Durham, North Carolina 27705, or [email protected] duke.edu Manuscript submitted April 2, 2001, and accepted in revised form January 31, 2002. 30 ©2002 by Excerpta Medica, Inc. All rights reserved. METHODS Subjects Generally healthy people who wanted to lose weight were recruited from the Raleigh/Durham/Chapel Hill areas in North Carolina. At a screening evaluation, we performed a medical history and physical examination, and obtained laboratory tests, urinary ketone measurement, and an electrocardiogram. Informed consent— using a form that was approved by the local Institutional Review Board—was obtained. There were no monetary incentives for participation. Inclusion/Exclusion Criteria The inclusion criteria were ages 18 to 65 years, body mass index from 26 to 33 kg/m2, a desire to lose weight, and no serious condition requiring medical supervision. Exclusion criteria were use of any prescription medication in 0002-9343/02/$–see front matter PII S0002-9343(02)01129-4 Very Low Carbohydrate Diet/Westman et al. the previous 2 months, pregnancy or breast-feeding, any weight loss diet during the past 6 months, use of prescription diet pills in the last 6 months, and baseline ketonuria. Intervention At a baseline visit (the first group meeting following enrollment), instruction in the diet program was provided and subjects were advised to begin the program on the following day. A very low carbohydrate diet (carbohydrate intake ⬍25 g/d) was recommended until 40% of a subject’s self-determined target weight loss was achieved (11). The daily amount of carbohydrate was then increased to about 50 g. The initial diet consisted of unlimited amounts of meat (i.e., beef, pork, chicken, turkey, fish, shellfish), unlimited eggs, cheese (4 ounces per day), salad vegetables (2 cups per day), and low-carbohydrate vegetables (1 cup per day). Portion sizes of meat and eggs were not restricted; subjects were instructed to eat until their hunger was relieved. There was no limit on the amount of caloric intake. Daily intake of at least six 8-ounce glasses of water was strongly encouraged. Nutritional supplements (multivitamin formula, essential oil formula, diet formula, chromium picolinate) were provided to subjects to be taken on a daily basis in divided doses (12) (Appendix). Aerobic exercise was encouraged at least 3 times per week (at least 20 minutes per session). No formal exercise program was provided. Group meetings were held every other week for 12 weeks, then every month for 3 months. At these meetings, a carbohydrate counter book and several handouts were given to subjects to reinforce the principles of the dietary program. The group meetings consisted of dietary counseling, supportive counseling, sharing of food choices, review of urinary ketone results, and collection of other measurements. The duration of each visit was approximately 1 hour. Outcome Measures Adherence with the diet was measured by self-report, food records, and urinary ketones. Adherence with exercise was assessed by self-report. A 7-day food record was completed during the second week of the program, and 24-hour food records were completed at the end of weeks 4 and 16. The total caloric intake, and percentage of dietary intake of protein, carbohydrate, and fat, were calculated by pooling this 9-day sampling (13). Food intake before the program was not assessed, but based on the subjects’ height and sex, the mean calculated recommended number of calories was approximately 1905 ⫾ 239 kcal/d (14). Because the intake of fewer than 40 g/d of carbohydrate results in urinary excretion of ketones, the presence of ketonuria was used to verify that subjects adhered to the diet recommendation (4,15). At each return visit, subjects provided a fresh urine specimen for visual analysis with a standard urine dipstick. Based on the color change of the dipstick, urinary ketones were assessed on the ordinal six-point scale: none (0 points), trace: 5 mg/dL (1 point), small: 5 to 40 mg/dL (2 points), moderate: 40 mg/dL (3 points), large: 80 mg/dL (4 points), large: 160 mg/dL (5 points). The mean level of ketonuria at return visits throughout the 6 months was categorized into a 3-level ordinal variable for each subject. Body weight was measured at each visit on the same scale, at approximately the same time of day (afternoon or evening), with the subject wearing light clothing but with shoes removed. Percentage change in body weight was calculated as: (baseline weight minus follow-up weight) / (baseline weight). Body mass index was calculated as: (body weight in kg) / (height in m)2. Using standard calipers, the skinfold thickness was measured in 4 body regions (anterior upper arm, posterior upper arm, abdomen, and subscapular skin) at baseline and at all visits. The total skinfold thickness was used to estimate body fat composition (16). At all return visits, blood pressure was measured in the nondominant arm, using an automated digital cuff after sitting for 3 minutes (Omron Model HEM-725C, Vernon Hills, Illinois) (17). Two measurements were taken at each visit and averaged for the analysis. Blood tests (sodium, potassium, bicarbonate, chloride, blood urea nitrogen, creatinine, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol, triglycerides, hemoglobin, hematocrit, white blood count, platelets, thyroid-stimulating hormone) were administered in the morning after at least 8 hours of fasting at the screening visit, 8 weeks, 16 weeks, and 24 weeks. Collection of 24-hour urine samples (creatinine, protein, calcium, uric acid) was on an outpatient basis at baseline, 8 weeks, 16 weeks, and 24 weeks. A creatinine sample ⬎1000 mg/d was considered to be adequate. At all return visits, subjects completed an open-ended adverse effects questionnaire. At the 20-week and 24-week visits, subjects completed a checklist of commonly mentioned adverse effects to estimate frequency of adverse effects. Statistical Analysis Paired t tests were used to compare measurements at baseline and 6 months. Dietary, nutritional supplement, and exercise adherence were also evaluated using linear regression as predictors of weight loss (18). A P value of ⬍0.05 was used for statistical significance. The sample size calculation was based on pilot data suggesting weight loss during a 6-month period of 13 ⫾ 28 kg. To detect this amount of weight reduction, with 80% power (2-sided ␣ of 0.05), about 50 subjects were required for the study (19). The Atkins Center for Complementary Medicine provided funding for the study, and educational training to July 2002 THE AMERICAN JOURNAL OF MEDICINE威 Volume 113 31 Very Low Carbohydrate Diet/Westman et al. Figure 1. Study participant flow. the research staff. Data collection, analysis, interpretation, and manuscript writing were conducted independently by the research staff. RESULTS Two hundred and sixty-eight people were screened by telephone and a health evaluation, 51 of whom were enrolled in the study and scheduled for the baseline visit. Forty-four subjects (86%) attended visits through 8 weeks, whereas 41 (80%) attended visits through 24 weeks (Figure 1). No subject dropped out due to symptomatic adverse effects; 9 were unable to comply with the diet program, and 1 became pregnant and discontinued the program. There were no significant differences in demographic characteristics or body weight between those who remained in the study and those who dropped out (Table 1). Fifty subjects (98%) had previously tried to lose weight using other weight loss programs, 39 (76%) had previously attempted to lose weight at least 2 times, 15 (29%) had previously used low-carbohydrate, high-protein diets, and 6 (12%) had previously used prescription medication for weight loss. At baseline, 16 subjects (31%) stated that they exercised 3 or more times per week. Program Adherence Of the 41 subjects who continued in the study, 27 (66%) reported following the dietary recommendations every day at 2 weeks, 25 (61%) at 12 weeks, and 15 (37%) at 24 weeks. Based on an average of 8 days of food records, the mean daily caloric intake was 1447 ⫾ 350 kcal (range, 801 to 2322 kcal). The mean daily diet composition was 23 ⫾ 32 July 2002 THE AMERICAN JOURNAL OF MEDICINE威 Volume 113 10 g of carbohydrate (range, 8 to 55 g), 115 ⫾ 29 g of protein (range, 63 to 229 g), and 98 ⫾ 27 g of fat (range, 42 to 168 g). Eighteen (44%) of 41 subjects reported taking the nutritional supplements every day as directed at 2 weeks, 19 (46%) at 12 weeks, and 20 (49%) at 24 weeks. Twenty-one (51%) reported following the exercise recommendation of exercising 3 or more times per week on average throughout the study period. All 41 subjects developed ketonuria. Eight subjects had a mean level of ketosis greater than “moderate” ketonuria (ⱖ3), 20 subjects had “moderate” to “trace” ketonuria (between 1 and 3), and 13 subjects averaged “trace” ketonuria or less (ⱕ1). The level of ketonuria was strongly correlated with self-reported dietary adherence (P ⫽ 0.002), but not with nutritional supplement adherence or exercise adherence. Table 1. Baseline Characteristics of the Subjects (n ⫽ 51) Characteristic 6-Month Adherers (n ⫽ 41) Dropouts (n ⫽ 10) P Value Number (%) or Mean ⫾ SD Age (years) Female sex White Body mass index (kg/m2) Height (m) Weight (kg) 43.7 ⫾ 8.9 31 (76) 30 (73) 31.4 ⫾ 2.8 39.8 ⫾ 5.7 7 (70) 5 (50) 32.5 ⫾ 2.4 0.10 0.72 0.16 0.28 1.66 ⫾ 0.89 87.0 ⫾ 11.1 1.64 ⫾ 0.95 90.4 ⫾ 9.3 0.83 0.34 Very Low Carbohydrate Diet/Westman et al. Figure 2. Effect of a very low-carbohydrate diet and nutritional supplements on body weight (n ⫽ 41). Fat mass estimated from skinfold thickness measurement. Fat-free mass ⫽ Body weight minus fat mass. Asterisk indicates P ⬍0.001 comparing change from week 0 to week 24. Error bars represent standard errors of the mean. Body Weight Thirty-nine (95%) of the 41 subjects who participated through 24 weeks lost weight. The overall body weight change from baseline to 24 weeks was ⫺10.3% ⫾ 5.9% (P ⬍0.001; range, 0% to 20.2%), representing a mean decrease in body mass index of 3.2 ⫾ 1.9 kg/m2 (range, 0 to 6.9 kg/m2) and in body weight of 9.0 ⫾ 5.3 kg (range, 0 to 18.6 kg; Figure 2). Nine subjects (22%) lost from 0% to 5% of body weight, 10 (24%) lost from 5% to 10%, 11 (27%) lost from 10% to 15%, 9 (22%) lost from 15% to 20%, and 2 (5%) lost ⬎20% of body weight. Weight loss correlated with dietary adherence (P ⬍0.01) and ketonuria (P ⬍0.01), but not with nutritional supplement or exercise adherence. Percentage of Body Fat Composition matocrit, white blood count, or platelet count. One 41year-old woman (height ⫽ 1.65 m, weight ⫽ 93.2 kg at baseline) had an increase in her thyroid-stimulating hormone level from 7.9 mU/mL at baseline to 13.3 mU/mL at 10 weeks, and was treated with a thyroid supplement by her physician. Beneficial effects on serum lipid levels were observed from baseline to 6 months (Table 3). Twenty-nine (71%) of the 41 subjects had a reduction in LDL cholesterol levels from baseline to 24 weeks. In the 12 subjects who had an increase in LDL cholesterol levels, the mean increase was 18 ⫾ 15 mg/dL (range, 4 to 53 mg/dL). Thirtyseven subjects (90%) had an increase in HDL cholesterol level from baseline to 24 weeks, but only 1 subject had an increase in the cholesterol/HDL cholesterol ratio. Fat mass calculated from skinfold thickness measurements decreased from 36.9 ⫾ 6.2 kg to 30.6 ⫾ 5.7 kg (P ⬍0.001; Figure 2). The nonfat mass decreased from 50.2 ⫾ 7.2 kg to 47.0 ⫾ 7.6 kg (P ⬍0.001). The mean calculated percentage of body weight that was fat decreased 2.9% ⫾ 3.2% (from 42.3% to 39.4%) during the study (P⬍ 0.001). Urine Tests Blood Tests Systolic blood pressure decreased 8 ⫾ 12 mm Hg from baseline to 24 weeks (P ⬍0.001), whereas diastolic blood pressure decreased 3 ⫾ 7 mm Hg (P ⬍0.01). There were statistically significant changes in serum levels of sodium, chloride, bicarbonate, uric acid, aspartate aminotransferase, total bilirubin, alkaline phosphatase, and blood urea nitrogen, and in the blood urea nitrogen/ creatinine ratio (Table 2). There were no significant changes in levels of creatinine or hemoglobin, or the he- There was a significant increase in urinary calcium excretion (P ⬍0.001) and uric acid excretion (P ⫽ 0.02) from baseline to 24 weeks. There was no significant change in 24-hour urine creatinine clearance or protein excretion during the 24 weeks (Table 3). Blood Pressure Adverse Effects At some point during the 24 weeks, 28 subjects (68%) reported constipation, 26 (63%) reported bad breath, 21 July 2002 THE AMERICAN JOURNAL OF MEDICINE威 Volume 113 33 Very Low Carbohydrate Diet/Westman et al. Table 2. Effect of Very Low Carbohydrate Diet Program on Metabolic Indices Parameter Baseline (n ⫽ 41) Week 8 (n ⫽ 41) Week 16 (n ⫽ 38) Week 24 (n ⫽ 41) Change from Baseline to Week 24 Mean Difference (95% Confidence Interval) P Value 139 ⫾ 1 103 ⫾ 2 25 ⫾ 2 5.0 ⫾ 1 22 ⫾ 9 0.8 ⫾ 0.3 69 ⫾ 15 15 ⫾ 5 0.8 ⫾ 0.2 19 ⫾ 5.5 ⫺3 (⫺4 to ⫺2) ⫺1 (⫺2 to 0) ⫺2 (⫺3 to ⫺1) ⫺0.3 (⫺1 to 0) ⫺4 (⫺6 to ⫺2) 0.1 (0 to 0.2) ⫺6 (⫺11 to ⫺1) 2 (1 to 3) ⫺0.1 (⫺0.13 to 0) 4 (3.8 to 4.1) ⬍0.001 0.02 ⬍0.001 0.01 0.002 ⬍0.001 0.02 ⬍0.001 0.06 ⬍0.001 Mean ⫾ SD Sodium (mmol/L) Chloride (mmol/L) Bicarbonate (mmol/L) Uric acid (mg/dL) Aspartate aminotransferase (U/L) Total bilirubin (mg/dL) Alkaline phosphatase (U/L) Blood urea nitrogen (mg/dL) Creatinine (mg/dL) Blood urea nitrogen/creatinine ratio 142 ⫾ 1 104 ⫾ 2 27 ⫾ 2 5.3 ⫾ 1 26 ⫾ 9 0.7 ⫾ 0.3 75 ⫾ 20 13 ⫾ 3 0.9 ⫾ 0.2 15 ⫾ 5 141 ⫾ 2 104 ⫾ 2 26 ⫾ 2 5.2 ⫾ 1 23 ⫾ 8 0.6 ⫾ 0.2 66 ⫾ 14 15 ⫾ 5 0.9 ⫾ 0.2 18 ⫾ 5 (51%) reported headache, 4 (10%) noted hair loss, and 1 woman (3%) reported increased menstrual bleeding. One subject reported an episode of orthostatic hypotension soon after restarting the diet after a period of nonadherence. This subject continued the diet program with no further similar episodes. Another subject had moderately severe headaches daily for 3 months, which resolved without treatment. Thirty-five subjects (85%) reported more energy, 11 (27%) had decreased heartburn, 30 (73%) had fewer cravings for sweets, 21 (51%) had improved mood, and 8 women (26%) had fewer premenstrual symptoms and less menstrual cramping. DISCUSSION In this 6-month uncontrolled study involving motivated, mildly obese persons, a very low carbohydrate diet pro- 140 ⫾ 2 104 ⫾ 3 24 ⫾ 2 5.2 ⫾ 1 23 ⫾ 9 0.7 ⫾ 0.2 65 ⫾ 14 16 ⫾ 5 0.8 ⫾ 0.2 20 ⫾ 5 gram led to a reduction in body weight that was similar to the effect of a medication recently approved for the treatment of obesity (20). Our findings were similar to those of a previous study using the same dietary approach but without nutritional supplementation or an exercise recommendation (9). In that study, 24 mildly overweight persons were instructed to follow a very low carbohydrate diet during an 8-week period. On average, subjects lost 7.7 kg of body weight, and the serum uric acid level increased from 5.9 to 7.7 mg/dL (P ⬍0.01). In contrast, we observed a reduction in serum uric acid levels, but found a statistically significant increase in urinary uric acid excretion. The self-reported food intake was similar in the 2 studies; in the previous study, subjects ingested a mean of 1461 kcal, 107 g of protein, 108 g of fat, and 6 g of carbohydrate per day (9). We estimate that in our study, 66% of the weight lost was Table 3. Effect of Very Low Carbohydrate Diet Program on Serum Lipid Level and 24-Hour Urinary Excretion Parameter Baseline (n ⫽ 41) Week 8 (n ⫽ 41) Week 16 (n ⫽ 38) Week 24 (n ⫽ 41) Change from Baseline to Week 24 Mean Difference (95% Confidence Interval) P Value Mean ⫾ SD Total cholesterol (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Non-HDL cholesterol (mg/dL) Triglycerides (mg/dL) Total cholesterol/HDL cholesterol ratio Triglycerides/HDL cholesterol ratio Urinary creatinine clearance (mL/min)* Urinary calcium (mg/24 h)* Urinary uric acid (mg/24 h)* Urinary protein (mg/24 h)* 214 ⫾ 35 136 ⫾ 32 52 ⫾ 14 162 ⫾ 37 130 ⫾ 62 4.3 ⫾ 1.3 2.8 ⫾ 2.0 124 ⫾ 30 162 ⫾ 109 540 ⫾ 202 119 ⫾ 54 201 ⫾ 37 136 ⫾ 36 49 ⫾ 11 152 ⫾ 39 82 ⫾ 32 4.3 ⫾ 1.2 1.8 ⫾ 1.0 126 ⫾ 33 289 ⫾ 152 630 ⫾ 337 145 ⫾ 85 201 ⫾ 42 128 ⫾ 39 58 ⫾ 13 143 ⫾ 42 75 ⫾ 30 3.6 ⫾ 1.0 1.4 ⫾ 0.7 128 ⫾ 38 306 ⫾ 159 542 ⫾ 240 130 ⫾ 53 203 ⫾ 36 126 ⫾ 34 62 ⫾ 15 141 ⫾ 37 74 ⫾ 33 3.4 ⫾ 0.9 1.3 ⫾ 0.9 129 ⫾ 26 248 ⫾ 120 635 ⫾ 155 134 ⫾ 50 ⫺11 (⫺19 to ⫺3) ⫺10 (⫺18 to ⫺2) 10 (8 to 12) ⫺21 (⫺29 to ⫺13) ⫺56 (⫺70 to ⫺42) ⫺0.9 (⫺1.1 to ⫺0.7) ⫺1.5 (⫺1.9 to ⫺1.1) 5 (⫺4 to 14) 86 (44 to 128) 95 (20 to 170) 15 (⫺10 to 40) * Urinary changes are assessed using a paired t test comparing baseline to week 24; n ⫽ 24 at each time point. HDL ⫽ high-density lipoprotein; LDL ⫽ low-density lipoprotein; non-HDL cholesterol ⫽ total cholesterol minus HDL cholesterol. 34 July 2002 THE AMERICAN JOURNAL OF MEDICINE威 Volume 113 0.006 0.01 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 0.33 ⬍0.001 0.02 0.25 Very Low Carbohydrate Diet/Westman et al. fat mass, similar to other studies involving dietary interventions for weight loss (21). Most subjects had a favorable change in their lipid profile. These findings are in contrast with 2 small studies of similar dietary interventions, in which one found an average increase in serum cholesterol level of 33 mg/dL after 1 week in 12 healthy volunteers, and the other reported a significant increase in LDL cholesterol level of 23 mg/dL (P ⬍0.01) (9,22). In our study, 1 subject had an increase in LDL cholesterol level from 123 mg/dL to 225 mg/dL, which then was reduced to 176 mg/dL with the addition of a cholesterol-lowering nutritional supplement formula while continuing the diet. In studies using other approaches for weight loss, this magnitude of weight loss has typically been associated with a reduction in total cholesterol levels of 13%, reduction in LDL cholesterol levels of 11%, reduction of triglyceride levels of 32%, and elevation in HDL cholesterol levels of 3% (23). We observed that levels of serum bicarbonate decreased and blood urea nitrogen increased during a very low carbohydrate diet program. Even though the serum bicarbonate levels in this study were still in the normal range, the long-term effects of a decreased bicarbonate level (mild metabolic acidosis) are not known. There was also an increase in urinary excretion of calcium and uric acid, possibly resulting from ketosis, proteinuria, or weight loss (24,25). Because dietary intake at baseline was not recorded, more precise measurement of calcium balance is needed to interpret these changes. Information about the potential adverse effects of carbohydrate restriction comes from 2 other diets. The “ketogenic diet” is a specific treatment for epilepsy that consists of a high-fat, low-carbohydrate, low-protein diet to induce the formation of ketone bodies (26). Adverse effects of this diet in children have included calcium oxalate and urate kidney stones (from 0.5% to 5.0% incidence in 1 year), vomiting, amenorrhea, hypercholesterolemia, and water-soluble vitamin deficiencies (27,28). The “protein-sparing modified fast” is a specific type of very lowcalorie diet, with extreme limitation of carbohydrate and calories (⬍800 kcal/d) (29,30). Because the very low-carbohydrate diet that we used provided more than 800 kcal/d, yet also led to ketonemia, it is probably most appropriately labeled as a “ketogenic low-calorie diet.” Limitations of this study include the uncontrolled design, self-report of several variables, and the use of skinfold calipers to estimate fat mass (31). Because only healthy volunteers were studied, caution should be used when generalizing these results to patients with medical illnesses. Although the dropout rate and adherence to this diet program are similar to that seen in other weight loss studies, the possibility of adverse effects in those who did not adhere to the program cannot be eliminated (32). In summary, this study describes the metabolic changes associated with a very low carbohydrate diet pro- gram when used for weight loss during a 6-month period. Further controlled research is needed to determine estimate the risks and benefits of this diet in healthy persons and in patients with other medical conditions. ACKNOWLEDGMENT Special thanks to Jacqueline Eberstein, Bill Bryson, and Lamont Wade. REFERENCES 1. Allison DB, Fontaine KR, Manson JE, et al. Annual deaths attributable to obesity in the United States. JAMA. 1999;282:1530 –1538. 2. Serdula MK, Mokdad AH, Williamson DF, et al. 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Am J Med. 2000;109:282–287. 36 July 2002 THE AMERICAN JOURNAL OF MEDICINE威 Volume 113 APPENDIX Ingredients of Nutritional Supplementation Multivitamin formula (administered daily in 6 capsules): Vitamin A as acetate (3000 IU), vitamin A as beta carotene with mixed carotenoids (1200 IU), vitamin C (360 mg), vitamin D3 (400 IU), vitamin E (300 IU), vitamin B1 (50 mg), vitamin B2 (50 mg), niacin (40 mg), vitamin B6 (50 mg), folate (1600 mg), vitamin B12 (800 g), vitamin K (10 g), biotin (600 g), pantothenic acid (120 mg), calcium (500 mg), magnesium (250 mg), zinc (50 mg), selenium (200 g), manganese (10 mg), chromium (600 g), molybdenum (60 g), potassium (20 mg), inositol hexanicotinate (100 mg), choline bitartrate (100 mg), para amino benzoic acid (100 mg), vanadyl (80 g), n-acetyl-l-cysteine (120 mg), pantethine (150 mg), quercetin (100 mg), boron (2 mg), grape seed extract (40 mg), green tea (80 mg). Unspecified amounts of lecithin extracts, garlic, arginine, licorice, bromelain, pantethine, spirulina, inulin, lactoferrin, bioperine, and acidophilus. Essential oil formula (administered daily in 3 capsules): flaxseed oil (1200 mg), borage seed oil (1200 mg), fish oil (1200 mg), vitamin E (15 IU). Diet formula (administered daily in 6 capsules): Citrin (2700 mg), chromium (1200 g), soy extract (9000 mg), methionine (1500 mg), l-carnitine (3000 mg), vitamin B6 (120 mg), pantethine (120 mg), asparagus (300 mg), parsley (300 mg), kelp (120 mg), spirulina (300 mg), potassium citrate (594 mg), magnesium (360 mg), l-glutamine (450 mg), dl-phenylalanine (900 mg), l-tyrosine (450 mg), piperine (30 mg).
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