Provident Perspective Volume 1, Issue 1

Provident News

On the Radio

Dr. Kevin C. Maki presented on a Radio Media Tour which aired in February. The interview on Heart Heath and Cholesterol reached over 33 million listeners and was heard on 657 radio stations across the US.

On Television

Dr. Kevin C. Maki was a key speaker in three Video News Releases this year. One was related to the launch of Enova Oil nationally by ADM-Kao joint ventures. The second was on the topic of lifestyle factors in the management of elevated cholesterol levels and the third covered the results of a trial to test the principles of the South Beach Diet for weight loss, the results of which were presented at the 2005 Experimental Biology meeting in San Diego.

Recent and Upcoming Publications and Presentations

Abstracts/Presentations

April 3, 2005. Maki KC, Rains TM, Kaden V, et al. A randomized, controlled clinical trial to evaluate the efficacy of a modified carbohydrate diet for reducing body weight and fat in overweight and obese men and women. FASEB J 2005;19:A771 (abstract #448.5). Experimental Biology, San Diego, CA.

April 4, 2005. Maki KC, Pearson TA, Galant R, Davidson MH. Dietary compliance and cholesterol goal achievement in patients with treated dyslipidemia. FASEB J 2005;19:A1024 (abstract #595.6). Experimental Biology, San Diego, CA.

April 4, 2005. Maki KC, Galant R, Samuel P, et al. Effects of consuming oat beta-glucan on blood pressure and carbohydrate metabolism in men and women with elevated blood pressure. FASEB J 2005;19:A1348 (abstract #747.2). Experimental Biology, San Diego, CA.

April 28, 2005. Kevin C. Maki, PhD. The Metabolic Syndrome: A Tangled Web of Risk Factors for Heart Disease and Diabetes. Wisconsin Dietetic Association annual conference, Eau Claire, Wisconsin.

May 12, 2005. Kevin C. Maki, PhD. Diet or Physical Inactivity. Which is the Major Cause of the Obesity and Diabetes Epidemics? Montana Dietetic Association annual conference, Helena, Montana.

Publications

Kevin C. Maki, Mary E. Van Elswyk, Deanna McCarthy, Serena P. Hess, Patricia E. Veith, Marjorie Bell, Papasani Subbaiah, Michael H. Davidson. Lipid Responses to a Dietary Docosahexaenoic Acid Supplement in Men and Women with Low Levels of High Density Lipoprotein Cholesterol. J Amer Coll Nutr 24: in press, June 2005.

In the Literature

This section of our newsletter briefly reviews one or two recently published papers that may be of interest to our clients. This month's paper is a highly controlled, inpatient study evaluating the effects of a very-low carbohydrate diet (Atkins) on appetite and other parameters.

Boden G., et al. Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diebetes. Ann Intern Med 2005;142:403-411.

Methods. The study was a controlled inpatient clinical trial of 10 obese patients with type 2 diabetes. Subjects were observed on their usual diet from days 1 through 7, followed by a low-carbohydrate (21 g/d) diet with unlimited access to food sources of protein and fat from days 8 through 21. Outcome measures included energy intake and expenditure, body weight and body water, glucose metabolism and insulin sensitivity.

Throughout days 1-21, all foods and beverages presented and all unconsumed portions were weighed and recorded. Basal metabolic rates were determined by indirect calorimetry with a metabolic cart. Body composition and body water were assessed via bioelectrical impedance analysis on days 1, 8 and 12. Total energy expenditure was determined using the doubly labeled water method for 6 of 10 patients. Euglycemic, hyperinsulinemic clamp tests were performed on days 1, 8 and 22 for assessment of insulin sensitivity. Glucose turnover using 6,6 2H2 glucose and glucose appearance and disappearance were assessed. Twenty-four-hour profiles for blood levels of glucose, insulin, leptin, and ghrelin were completed on days 7 and 21.

Results. Body weight was stable during the usual diet period. The low carbohydrate diet, after subtracting body water, resulted in a mean body weight change of -1.65 kg. The mean difference between energy expenditure and intake was 1027 kcal/d during the low-carbohydrate period. Body fat accounted for the entire loss of non-water body weight. Actual loss of non-water body weight was nearly identical to the loss of 1.60 kg predicted based on energy balance. No increases were observed in ratings of hunger, despite the large daily energy deficit.

The low carbohydrate diet improved glycemic control (hemoglobin A1C declined from 7.3% to 6.8%), insulin sensitivity increased by 75% without any change in the rate of endogenous glucose appearance. Serum triglycerides decreased by 35%, the total cholesterol concentration declined by 10% and LDL and HDL cholesterol levels were unchanged. Mean 24-hour plasma concentrations of glucose, insulin and leptin were significantly reduced and mean ghrelin concentration was slightly increased.

Conclusions. In this strictly supervised inpatient study, short-term use of a low-carbohydrate diet in obese patients with type 2 diabetes resulted in markedly negative energy balance due to reduced spontaneous energy intake (i.e., protein and fat intakes did not increase in response to carbohydrate restriction). Additional research is needed to evaluate the long-term effects of such diets.

Comments from Dr. Maki. As many of the readers of this newsletter are aware, I have been interested for some time in the hepatostatic theory of food intake regulation. According to this theory, the rate of hepatic fat oxidation, relative to the level of hepatic glycogen stores, influences the generation of neural and/or endocrine “satiety signals” from the liver. Thus, higher hepatic fat oxidation (for a given level of liver glycogen) may reduce appetite. This might be expected to occur on a low-carbohydrate diet because reduced day-long insulin levels would lead to a down-regulation of liver glycogen stores while enhancing hepatic fat oxidation (in response to reduced hepatic glucose oxidation). The results outlined by Boden and colleagues suggest that appetite is dramatically suppressed during short-term consumption of a very-low-carbohydrate diet, consistent with the hepatostatic theory.

The most important question then becomes what happens over longer periods. A number of trials have shown greater weight loss over periods of 3-6 months during consumption of a reduced carbohydrate diet. While I have concerns about the long-term health effects of such diets, this study provides new insights into short-term regulation of energy intake associated with very-low-carbohydrate diets and adds further support (though indirect) for a possible role of hepatic fat oxidation in the regulation of energy intake. Additional evaluation of the mechanisms responsible for these effects may provide useful insights for the design of interventions intended to aid in the prevention and management of obesity.

About Provident

Provident has a team of research professionals with extensive experience in the design and conduct of clinical trials to evaluate pharmaceuticals, medical and functional foods, dietary supplements and medical devices.

For more information, visit our web site: http://www.providentcrc.com.

Or, contact us directly:

Tia Rains: trains@providentcrc.com, Director of Medical Writing / Principal Scientist