In the midst of confusion lies opportunity: fostering quality science in dietary supplement research.

The Office of Dietary Supplements (ODS) was established at the National Institutes of Health (NIH) by Congress through the Dietary Supplement Health and Education Act (DSHEA) of 1994. The mission of the ODS is to strengthen knowledge and understanding of dietary supplements by evaluating scientific information, stimulating and supporting research, disseminating research results and educating the public, all in an effort to foster an enhanced quality of life and health for the U.S. population. In pursuit of this mission, ODS takes into account an array of dietary supplement ingredients and products. This includes vitamin and mineral supplements and botanicals, as well as non-nutrient supplements. Toward that end, ODS has taken a number of steps. In collaboration with other Institutes and Centers at NIH, ODS has established a network of Dietary Supplement Research Centers around the country that provide the focus for multidisciplinary research efforts; it supports research activities and scientific conferences, it supports evidence-based reviews of supplements, and it maintains a public database of scientific literature on dietary supplements. The lack of credible information from well-controlled studies of many dietary supplements raises issues of caution and concern. The ODS is committed to providing and disseminating accurate and reliable scientific information on dietary supplements.

Magnesium supplementation in patients with congestive heart failure.

OBJECTIVE: To evaluate several potential clinical indicators of magnesium status (diet, blood, urine, 24-hour load retention) in patients with congestive heart failure before, during, and after oral magnesium supplementation. METHODS: Twelve patients with New York Heart Association class II-III heart failure and 12 age and sex matched healthy control subjects were supplemented with 10.4 mmol oral magnesium lactate for 3 months. For the determination of magnesium status, samples of whole blood, serum, plasma, red blood cells, and urine (24-hour) were collected. Four-day dietary intake records were reviewed. A 4-hour IV magnesium load retention study was performed before and 3 months after magnesium supplementation. A non-supplemented control group was similarly studied. RESULTS: At baseline, magnesium intakes for all groups were below the RDA. No significant differences were seen in serum, plasma, ultrafiltrates of serum or plasma or red cell magnesium concentrations among groups over time. At baseline 5/27 subjects (19%) compared to 11/27 subjects (41%) after supplementation demonstrated normal magnesium retentions (< 25%). Magnesium excretions among groups were significantly different during supplementation. Percent magnesium retentions among groups were not different. CONCLUSIONS: Supplementation with 10.4 mmol oral magnesium daily for 3 months did not significantly alter blood levels or magnesium retention; however, patients demonstrated lower retention of magnesium after supplementation. Differences in magnesium retention was not related to basal magnesium intake, blood levels or excretion. Unfortunately, even an intensive effort at characterizing magnesium status did not identify a clinical indicator of utility for differentiating patients with congestive heart failure before, during, and after 3 months of magnesium supplementation.

A review of magnesium intake in the elderly. A cause for concern?

Elderly people in the United States represent an emerging high risk group for nutritional deficiencies. A magnesium deficit in the elderly can occur due to inadequate nutrient intakes, multiple drug use, or altered gastrointestinal function. Magnesium has been targeted as a risk factor for elderly people and has been implicated in the aging process. Data presented in this review confirm decreased availability of magnesium in the food supply, lower intakes of magnesium by elderly people, and widespread supplementation practices. Conflicting data exist regarding levels of magnesium in the blood and magnesium status in the elderly. It is not known to what extent suboptimal intakes may affect the aging process; however, magnesium-deficient conditions have been associated with neuromuscular and cardiovascular disorders, endocrine disturbances, insulin resistance and Alzheimer's disease.

Effect of acebutolol on left ventricular performance.

The effect of acebutolol on left ventricular performance was examined by various noninvasive means in three studies. M-mode echocardiographic measurements were made in 21 patients with coronary artery disease who were receiving placebo, acebutolol, and propranolol in a double-blind, randomized, crossover study. In these patients with normal or near-normal resting left ventricular function, neither drug induced depression of left ventricular function. In 26 patients with chronic angina pectoris receiving acebutolol under double-blind, placebo-controlled conditions, gated (equilibrium) myocardial blood pool imaging using red blood cells labeled with technetium 99m showed acebutolol to have no clinically significant negative effect on left ventricular performance at rest or during supine bicycle exercise. Acebutolol at effective antianginal doses modestly improved resting global and regional myocardial function. In 13 patients with stable angina pectoris, single-pass studies of left ventricular function with indium 113 under double-blind, placebo-controlled conditions similarly showed acebutolol to have no clinically significant negative inotropic effects. In conclusion, acebutolol is safe for use in patients with coronary disease and a wide range of ejection fractions but, as with all beta blockers, should be used cautiously in patients with markedly reduced resting left ventricular function.

Bepridil for chronic stable angina pectoris: results of a prospective multicenter, placebo-controlled, dose-ranging study in 77 patients.

Bepridil, a new calcium-channel blocking agent with an extended plasma elimination half-life of greater than 50 hours, was compared to placebo in 77 patients with confirmed coronary artery disease and chronic stable angina pectoris. The effects of bepridil were compared with those of placebo on angina frequency, nitroglycerin tablet use, the resting ECG and hemodynamics at rest and maximal exercise using a study design comprising 5 sequential 2-week single-blind treatment phases. After 2 weeks of placebo (phase 1), bepridil was given for 3 phases (2, 3 and 4) at total daily dosages of 200, 300 and 400 mg, respectively; the study was completed after a final reintroduction of placebo (phase 5). Within each phase once- and twice-daily regimens of bepridil were randomly compared. Bepridil (300 mg/day) reduced anginal frequency 68%, from 8.5 +/- 1.1 (standard error of the mean) to 2.7 +/- 0.7 attacks/week and nitroglycerin tablet use 76% (p less than 0.001). Bepridil improved exercise duration 26%, from 6.9 +/- 0.4 to 8.7 +/- 0.5 minutes (p less than 0.001) and exercise work 52%, from 2.7 +/- 0.3 to 4.1 +/- 0.4 kpm X 10(-3) (p less than 0.001) on a standardized treadmill protocol. Resting and peak exercise heart rate and blood pressure were unaffected by bepridil. The antianginal effects were similar with either once- or twice-daily treatment schedules. Minor side effects of nausea, epigastric discomfort and tremor were infrequent and there were no major side effects. The results of this large but preliminary, single-blind and short-term study suggest that bepridil is an effective and well tolerated antianginal agent when administered once daily.

Glucose and lipid metabolism during acebutolol and propranolol therapy of angina in nondiabetic patients.

The metabolic effects of acebutolol, a cardioselective beta-adrenergic blocker, and of propranolol, a nonselective beta blocker, were evaluated. Our subjects were 20 men with chronic stable angina; none had diabetes. An initial 4-wk, single-blind control phase was followed by two drug treatment periods, each a 3-wk double-blind titration phase (using increasing doses of acebutolol or propranolol), followed by a 5-wk double-blind maintenance phase. Metabolic studies were performed at the end of the control and maintenance phases. Propranolol induced elevation in basal serum glucose concentrations and both propranolol and acebutolol decreased glucose tolerance at 2.5 and 3 hr. There was no noticeable effect on insulin secretion by either drug. Neither propranolol nor acebutolol induced hyperlipidemia. There was a small decrease in total serum cholesterol after propranolol. Both drugs decreased low-density lipoprotein cholesterol. No effects were noted on the levels of serum triglycerides, high-density lipoprotein cholesterol, or free fatty acids.

Pulmonary effects of acebutolol, a "cardioselective" beta adrenergic blocking agent.

The effect of chronic oral therapy with acebutolol, a cardioselective beta adrenergic blocking agent, was evaluated on resting pulmonary functions in a group of patients who were free of overt obstructive airways disease and who had chronic stable angina pectoris. The study design involved a 20-week, placebo-controlled, double-blind, randomized cross-over trial, using acebutolol, an agent with partial agonist activity that has been shown to be effective in the treatment of hypertension, cardiac arrhythmias, and angina pectoris. Utilizing spirometry, flow volume loops, and arterial blood gas analyses, this study demonstrated that acebutolol had no significant deleterious effect on resting pulmonary function when used in clinically effective dosages.