Eric C. Westman

A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial.

Context Low-carbohydrate weight reduction diets are popular despite a dearth of data on long-term efficacy and adverse effects. Contribution Community-dwelling hyperlipidemic persons were randomly assigned to either a low-carbohydrate, ketogenic diet or a low-fat, low-cholesterol, reduced-calorie diet for 24 weeks. Compared to the low-fat group, patients in the low-carbohydrate group lost more weight, had a greater decrease in triglyceride levels, and had higher high-density lipoprotein cholesterol levels. Levels of low-density lipoprotein cholesterol remained stable in both groups. Side effects were more common in the low-cholesterol group but were generally mild. Cautions While the study suggests the efficacy and relative safety of the low-cholesterol diet, the high dropout rate, self-directed adherence to the diet, and relatively short observation period challenge the generalizability of the findings. The Editors As the prevalence of obesity has increased over the past 20 years (1), the difficulties faced by overweight patients and their health care practitioners have become apparent. Fewer than 25% of Americans who attempt to lose weight actually reduce caloric intake and increase exercise as currently recommended (2). Persons who successfully lose weight have difficulty maintaining their weight loss (3). Therefore, it is not surprising that consumers spend

The Safety of Transdermal Nicotine as an Aid to Smoking Cessation in Patients with Cardiac Disease

33 billion yearly on weight loss products and services in search of effective therapies (2). Because many weight loss interventions are unproven and untested, practitioners often lack information with which to recommend a certain therapy or to monitor a patient once a therapy is chosen. One approach to weight loss that has gained recognition in the face of modest supportive scientific evidence is the low-carbohydrate diet. A popular version of this diet recommends extreme restriction of carbohydrate intake to less than 20 g/d initially (4). This level of carbohydrate restriction can induce serum and urinary ketones and weight loss (5, 6). However, until recently, available data on low-carbohydrate diets came from small studies of short duration, most of which were uncontrolled (5, 7-10). We examined body weight, body composition, serum lipid levels, and adverse effects over 24 weeks in hyperlipidemic persons who were randomly assigned to follow a low-carbohydrate, ketogenic diet or a low-fat, low-cholesterol, reduced-calorie diet commonly used to induce weight loss and decrease serum lipid levels. Methods Participants Generally healthy persons were recruited from the community. Inclusion criteria were age 18 to 65 years, body mass index of 30 to 60 kg/m2, desire to lose weight, elevated lipid levels (total cholesterol level > 5.17 mmol/L [>200 mg/dL], low-density lipoprotein [LDL] cholesterol level > 3.36 mmol/L [>130 mg/dL], or triglyceride level > 2.26 mmol/L [200 mg/dL]), and no serious medical condition. Exclusion criteria were use of any prescription medication in the previous 2 months (except for oral contraceptives, estrogen therapy, and stable thyroid medication), pregnancy or breastfeeding, use of any weight loss diet or diet pills in the previous 6 months, and baseline ketonuria. All participants provided written informed consent, and the institutional review board of Duke University Health System approved the study. Participants received no monetary incentive. Interventions By using a computer-generated simple randomization list, participants were allocated to receive the low-carbohydrate diet or low-fat diet. The intervention for both groups included group meetings, diet instruction, and an exercise recommendation. Group meetings took place at an outpatient research clinic twice monthly for 3 months, then monthly for 3 months. These meetings typically lasted 1 hour and consisted of diet instruction, supportive counseling, questionnaires, and biomedical measurements. During the study, participants selected their own menus and prepared or bought their own meals according to the guidelines presented to them. Participants were encouraged to exercise for 30 minutes at least 3 times weekly, but no formal exercise program or incentives were provided. Low-Carbohydrate Diet Using a popular diet book published by a lay press and additional handouts, trained research staff instructed participants to restrict intake of carbohydrates to less than 20 g/d (4). Participants were permitted unlimited amounts of animal foods (meat, fowl, fish, and shellfish), unlimited eggs, 4 oz of hard cheese, 2 cups of salad vegetables (such as lettuce, spinach, or celery), and 1 cup of low-carbohydrate vegetables (such as broccoli, cauliflower, or squash) daily. Participants were encouraged to drink 6 to 8 glasses of water daily. When participants were halfway to their goal body weight (determined at the week 10 visit with assistance from research personnel), they were advised to add approximately 5 g of carbohydrates to their daily intake each week until they reached a level at which body weight was maintained. To simulate the practice of the study sponsor, the low-carbohydrate diet group also received daily nutritional supplements (multivitamin, essential oils, diet formulation, and chromium picolinate; for a list of the composition of these supplements, see the Appendix) (6). Low-Fat Diet Using a commonly available booklet and additional handouts, a registered dietitian instructed participants in a diet consisting of less than 30% of daily energy intake from fat, less than 10% of daily energy intake from saturated fat, and less than 300 mg of cholesterol daily (11, 12). The recommended energy intake was 2.1 to 4.2 MJ (500 to 1000 kcal) less than the participants calculated energy intake for weight maintenance (body weight in pounds 10) (13). Primary Outcome Measure Body weight and body mass index were the primary outcome measures. At each visit, participants were weighed on the same calibrated scale while wearing lightweight clothing and no shoes. Body mass index was calculated as body weight in kilograms divided by height in meters squared. Secondary Outcome Measures Adherence Adherence to the diet was measured by self-report, food records, and, for the low-carbohydrate diet group, urinary ketone assessment. Diet Composition All participants completed a 24-hour recall of food intake at baseline and take-home food records (5 consecutive days, including a weekend) that were collected at each meeting during the study. Participants were instructed on how to document food intake and were given handouts with examples of how to complete the records. A sample of participants (13 in the low-carbohydrate diet group and 7 in the low-fat diet group) who completed the study was selected for food record analysis by the research staff on the basis of adequacy of detail in their records. A registered dietitian analyzed the food records by using a nutrition software program (Nutritionist Five, version 1.6 [First DataBank, Inc., San Bruno, California]). Ketonuria Restriction of dietary intake of carbohydrates to less than 40 g/d typically results in ketonuria that is detectable by dipstick analysis, which can be used to monitor adherence to the low-carbohydrate diet (14, 15). At each return visit, participants provided a fresh urine specimen for analysis. The following semi-quantitative scale was used to categorize ketone content: none, trace (up to 0.9 mmol/L [5 mg/dL]), small (0.9 to 6.9 mmol/L [5 to 40 mg/dL]), moderate (6.9 to 13.8 mmol/L [40 to 80 mg/dL]), large80 (13.8 to 27.5 mmol/L [80 to 160 mg/dL]), and large160 (>27.5 mmol/L [>160 mg/dL]). Body Composition Body composition was estimated by using bioelectric impedance (model TBF-300A [Tanita Corp., Arlington Heights, Illinois]) at approximately the same time of day (afternoon or evening) at each return visit. In a subset of 33 participants, the percentage of body fat as measured by bioelectric impedance had excellent correlation with the percentage as measured by dual-energy x-ray absorptiometry (r = 0.93 [95% CI, 0.87 to 0.97]). Vital Signs Blood pressure and pulse rate were measured in the nondominant arm by using an automated digital cuff (model HEM-725C [Omron Corp., Vernon Hills, Illinois]) after the participant had been sitting for 3 minutes. Two measurements were taken at each visit and averaged for the analysis. Serum Lipids and Lipoproteins Serum specimens for lipid measurement were obtained in the morning after at least 8 hours of fasting at the screening visit and at 8, 16, and 24 weeks. Other Metabolic Effects Serum tests for sodium, potassium, chloride, urea nitrogen, creatinine, calcium, phosphorus, total protein, albumin, uric acid, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, thyroid-stimulating hormone, iron, hemoglobin, leukocyte count, and platelet count were obtained at the screening visit and at 8, 16, and 24 weeks. The glomerular filtration rate was estimated by using an equation that included age; sex; race; and serum levels of albumin, creatinine, and urea nitrogen (Modification of Diet in Renal Disease Study equation) (16). Adverse Effects At all return visits, participants completed an open-ended questionnaire on side effects. At the 20- and 24-week visits, participants completed a checklist of the side effects that were most often mentioned during the study. Statistical Analysis Analyses were performed by using S-PLUS software, version 6.1 (Insightful Corp., Seattle, Washington), or SAS software, version 8.02 (SAS Institute, Inc., Cary, North Carolina). For categorical outcomes, groups were compared by using the chi-square test or Fisher exact test, as appropriate. For all primary and secondary continuous outcomes, linear mixed-effects models (PROC MIXED procedure in SAS software) that included fixed and random effects were used to determine expected mean values at each time point and to test hypotheses of group differences. In most body weight and b

Effect of 6-month adherence to a very low carbohydrate diet program

BACKGROUND Transdermal nicotine therapy is widely used to aid smoking cessation, but there is uncertainty about its safety in patients with cardiac disease. METHODS In a randomized, double-blind, placebo-controlled trial at 10 Veterans Affairs medical centers, we randomly assigned 584 outpatients (of whom 576 were men) with at least one diagnosis of cardiovascular disease to a 10-week course of transdermal nicotine or placebo as an aid to smoking cessation. The subjects were monitored for a total of 14 weeks for the primary end points of the study (death, myocardial infarction, cardiac arrest, and admission to the hospital due to increased severity of angina, arrhythmia, or congestive heart failure); the secondary end points (admission to the hospital for other reasons and outpatient visits necessitated by increased severity of heart disease); any side effects of therapy; and abstinence from smoking. RESULTS There were 48 primary and 78 secondary end points noted in a total of 95 subjects. At least one of the primary end points was reached by 5.4 percent of the subjects in the nicotine group and 7.9 percent of the subjects in the placebo group (difference, 2.5 percent; 95 percent confidence interval, -1.6 to 6.5 percent; P=0.23). In the nicotine group, 11.9 percent of the subjects had at least one of the secondary end points, as compared with 9.7 percent in the placebo group (difference, 2.2 percent; 95 percent confidence interval, -2.2 to 7.4 percent; P= 0.37). After 14 weeks the rate of abstinence from smoking was 21 percent in the nicotine group, as compared with 9 percent in the placebo group (P=0.001), but after 24 weeks the abstinence rates were not significantly different (14 percent vs. 11 percent, P= 0.67). CONCLUSIONS Transdermal nicotine does not cause a significant increase in cardiovascular events in high-risk outpatients with cardiac disease. However, the efficacy of transdermal nicotine as an aid to smoking cessation in such patients is limited and may not be sustained over time.

Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone

To determine the effect of a 6-month very low carbohydrate diet program on body weight and other metabolic parameters.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.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/m(2)). 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.A very low carbohydrate diet program led to sustained weight loss during a 6-month period. Further controlled research is warranted.

Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base

To evaluate concurrent administration of mecamylamine (nicotine antagonist) with nicotine skin patch treatment for smoking cessation.

The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus.

The inability of current recommendations to control the epidemic of diabetes, the specific failure of the prevailing low-fat diets to improve obesity, cardiovascular risk, or general health and the persistent reports of some serious side effects of commonly prescribed diabetic medications, in combination with the continued success of low-carbohydrate diets in the treatment of diabetes and metabolic syndrome without significant side effects, point to the need for a reappraisal of dietary guidelines. The benefits of carbohydrate restriction in diabetes are immediate and well documented. Concerns about the efficacy and safety are long term and conjectural rather than data driven. Dietary carbohydrate restriction reliably reduces high blood glucose, does not require weight loss (although is still best for weight loss), and leads to the reduction or elimination of medication. It has never shown side effects comparable with those seen in many drugs. Here we present 12 points of evidence supporting the use of low-carbohydrate diets as the first approach to treating type 2 diabetes and as the most effective adjunct to pharmacology in type 1. They represent the best-documented, least controversial results. The insistence on long-term randomized controlled trials as the only kind of data that will be accepted is without precedent in science. The seriousness of diabetes requires that we evaluate all of the evidence that is available. The 12 points are sufficiently compelling that we feel that the burden of proof rests with those who are opposed.

Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction

ObjectiveDietary carbohydrate is the major determinant of postprandial glucose levels, and several clinical studies have shown that low-carbohydrate diets improve glycemic control. In this study, we tested the hypothesis that a diet lower in carbohydrate would lead to greater improvement in glycemic control over a 24-week period in patients with obesity and type 2 diabetes mellitus.Research design and methodsEighty-four community volunteers with obesity and type 2 diabetes were randomized to either a low-carbohydrate, ketogenic diet (<20 g of carbohydrate daily; LCKD) or a low-glycemic, reduced-calorie diet (500 kcal/day deficit from weight maintenance diet; LGID). Both groups received group meetings, nutritional supplementation, and an exercise recommendation. The main outcome was glycemic control, measured by hemoglobin A1c.ResultsForty-nine (58.3%) participants completed the study. Both interventions led to improvements in hemoglobin A1c, fasting glucose, fasting insulin, and weight loss. The LCKD group had greater improvements in hemoglobin A1c (-1.5% vs. -0.5%, p = 0.03), body weight (-11.1 kg vs. -6.9 kg, p = 0.008), and high density lipoprotein cholesterol (+5.6 mg/dL vs. 0 mg/dL, p < 0.001) compared to the LGID group. Diabetes medications were reduced or eliminated in 95.2% of LCKD vs. 62% of LGID participants (p < 0.01).ConclusionDietary modification led to improvements in glycemic control and medication reduction/elimination in motivated volunteers with type 2 diabetes. The diet lower in carbohydrate led to greater improvements in glycemic control, and more frequent medication reduction/elimination than the low glycemic index diet. Lifestyle modification using low carbohydrate interventions is effective for improving and reversing type 2 diabetes.

Nicotine-mecamylamine treatment for smoking cessation: The role of pre-cessation therapy.

An understanding of drug addiction requires knowledge of the effective drug concentrations to which receptors in the nervous system are exposed. It has often been thought that smoking of abused substances such as nicotine or cocaine produces much higher drug concentrations in the arterial blood than those achieved following any other route of administration. However, to date no studies have sampled arterial blood following cigarette smoking with the rapidity necessary to evaluate this hypothesis. We measured arterial plasma nicotine concentrations in samples collected every 5 s from 13 cigarette smokers during cigarette smoking and during administration of nicotine by intravenous injections. Our results show that, for both routes of administration, concentrations of nicotine in arterial blood were more than 10 times lower than expected. Thus, the delivery of nicotine into arterial blood is substantially slower than would be predicted if nicotine were absorbed as rapidly as has generally been assumed. A plausible explanation of these results is that lung uptake of nicotine considerably slows the entry of nicotine into the systemic circulation, as has been shown for other amines. These results have significant implications for theories of addiction to nicotine as well as other drugs such as cocaine that may be subject to binding by lung tissue.

Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal

The nicotinic antagonist mecamylamine was evaluated in a randomized smoking cessation trial. Four groups of participants (n = 20 per group) received nicotine plus mecamylamine, nicotine alone, mecamylamine alone, or no drug for 4 weeks before cessation. After the quit-smoking date, all subjects received nicotine plus mecamylamine treatment for 6 weeks. Nicotine skin patches (21 mg/24 hr) and mecamylamine capsules (2.5-5.0 mg twice per day) were used. Precessation mecamylamine significantly prolonged the duration of continuous smoking abstinence; abstinence rates at the end of treatment were 47.5% with mecamylamine and 27.5% without mecamylamine. Nicotine + mecamylamine reduced ad lib smoking, smoking satisfaction, and craving more than either drug alone. Moreover, the orthostatic decrease in blood pressure caused by mecamylamine was offset by nicotine. Mecamylamine before smoking cessation may be an effective adjunct to nicotine patch therapy.

A low-carbohydrate, ketogenic diet to treat type 2 diabetes

Current nutritional approaches to metabolic syndrome and type 2 diabetes generally rely on reductions in dietary fat. The success of such approaches has been limited and therapy more generally relies on pharmacology. The argument is made that a re-evaluation of the role of carbohydrate restriction, the historical and intuitive approach to the problem, may provide an alternative and possibly superior dietary strategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulin fluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrate is generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restriction do not require weight loss. Finally, the point is reiterated that carbohydrate restriction improves all of the features of metabolic syndrome.