Clinical Briefs With Comments from Russell H. Greenfield, MD
Clinical Briefs
With Comments from Russell H. Greenfield, MD, Dr. Greenfield is Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, NC; and Visiting Assistant Professor, University of Arizona, College of Medicine, Tucson, AZ.
Male and Frail: Androgen Supplementation?
Source: Muller M, et al. Effects of dehydroepiandrosterone and atamestane supplementation on frailty in elderly men. J Clin Endocrinol Metab 2006;91:3988-3991. Epub 2006 Jun 27.
Goal: To determine whether hormone replacement therapy with dehydroepi-androsterone (DHEA) and/or atamestane improves age-related frailty (ARF) in elderly men.
Design: Double-blind, randomized, controlled trial completed over 36 weeks.
Subjects: Independently living Dutch men older than age 70 years with low strength test scores (n = 100 selected from 400 who had participated in a prior study, complete data available for 83).
Methods: Following completion of fasting baseline assessments, including blood samples and measures of strength/frailty and cognition, participants were randomized to one of four different groups: atamestane 100 mg/d and placebo; DHEA 50 mg/d and placebo; combined atamestane 100 mg/d and DHEA 50 mg/d; two placebo tablets daily (all were to be taken at breakfast). Subjects had a total of seven clinic visits, with the last visit being 24 weeks after the last tablet was ingested. Outcome measures included muscle strength, physical frailty, functional performance, cognition, general well-being, bone mineral density, and body composition.
Results: DHEAS levels increased in the DHEA groups, while total testo-sterone levels increased in all three intervention groups. No differences were noted in any of the outcome measures studied between the placebo group and the groups that received various interventions.
Conclusion: Hormone replacement therapy with atamestane 100 mg/d and/or DHEA 50 mg/d does not improve the course of ARF in men.
Study strengths: Outcome measures chosen; intention-to-treat analysis; duration of trial.
Study weaknesses: Participants had normal testosterone levels at baseline; dropout rate of 17% (but no difference in rate among the groups); compliance measured by pill count, and with a liberal cutoff for noncompliance (< 80%).
Of note: Studies suggest that age-related declines in male hormones may play a role in ARF; results of research employing DHEA for the treatment of ARF have been contradictory, with some showing benefits in muscle strength and body composition, and others showing no benefit; studies employing testosterone supplementation have reported improvements in cognition and bone mineral density, as well as muscle mass and strength, but at the expense of increased prostate size; subjects with a history of prostate cancer were excluded from the trial; IGF-1 levels increased only in the atamestane/DHEA group; body mass index measurements increased in both the atamestane and DHEA groups.
We knew that: ARF is characterized by generalized weakness, decreased endurance, poor mobility, limited flexibility, and impaired balance, which is associated with an increased incidence of disability; atamestane is an aromatase inhibitor that has been shown to increase testosterone levels in elderly men by 30-50% while simultaneously decreasing estradiol levels.
Clinical import: A segment of the medical community now concerns itself with "anti-aging" therapies, including means of addressing andropause, the gradual age-related decrease in male hormones that may be associated with changes in body composition and functionality. In parallel to the previously long-favored approach to menopause, the idea of hormone replacement therapy for men garnered significant interest. Results of some studies created a buzz with data suggesting improved energy, stamina, and strength, but concerns about the potential risks associated with long-term androgen administration, notably fears over the possibility of an increased risk of prostate cancer, tempered initial enthusiasm. The present study at hand revealed no improvements in frailty with either DHEA or an agent that indirectly increases testosterone levels. Some will argue that higher doses should have been employed, or that subjects with low levels of DHEA or testosterone should have been the focus of the trial. Regardless, using hormone replacement therapy to try to stave off the effects of aging may be fraught with problems, if not frank dangers. Until there is clear evidence of benefit and definitive data regarding lack of increased risk for prostate cancer, androgen supplementation to prevent the effects of aging should be avoided. The goal for us all is to safely get older without growing older. Thankfully, many lifestyle and dietary interventions alone may help us achieve that goal.
What to do with this article: Keep a copy of the abstract on your computer.
"Coffee, No Sugar"—Coffee and IGT
Source: Smith B, et al. Does coffee consumption reduce the risk of type 2 diabetes in individuals with impaired glucose? Diabetes Care 2006;29:2385-2390.
Goal: To compare the coffee habits of people with impaired glucose control (IGT) to those with normal baseline glucose levels, and examine the relationship between coffee intake and incident diabetes mellitus (DM).
Study design: Prospective.
Subjects: Adults from Southern California older than age 50 years (n = 910, average age 65.9) who had previously participated in the Rancho Bernardo Study (RBS) in the 1970s and were without DM at baseline; 317 had impaired baseline glucose levels.
Methods: Between 1980 and 1984, 80% of the survivors of the RBS completed a baseline DM evaluation, and then a subsequent follow-up evaluation in 1992-1996 (74% of survivors). At each visit, anthropometric measures were obtained together with a complete history and blood tests. An oral 75 g glucose load was administered in the morning following an overnight fast, with blood drawn both before the glucose load and two hours thereafter. Subjects were followed for an average of eight years (up to 11 years). In 1992, a mailed survey was completed that included information on current and lifetime drinking of coffee, both caffeinated and decaffeinated (to be analyzed separately). Logistic regression models were employed and adjusted for multiple potential confounders including gender, age, physical activity, body mass index, smoking, alcohol, and hypertension.
Results: At baseline only 97 subjects reported never drinking coffee, while 153 were past drinkers, and 660 were current coffee drinkers (average of 2.8 cups/d). The number of cups of coffee imbibed each day, coffee consumption after age 45, and number of cup-years were not associated with risk of DM. Subjects who regularly drank coffee, either in the past or currently, had a reduced risk of incident DM (odds ratio [OR] = 0.38 and 0.36, respectively) compared with those who never drank coffee. Subjects who had impaired glucose at baseline and who were past or current coffee drinkers also were at reduced risk for development of DM (OR = 0.31 and 0.36, respectively).
Conclusion: Caffeinated coffee provides a significant protective effect against development of DM independent of multiple potential confounders. In contrast to the findings of some other trials, the quantity of coffee ingested daily does not predict impact on later risk of developing DM.
Study strengths: Use of oral glucose tolerance test (OGTT); duration of follow-up.
Study weaknesses: Self-reporting (potential recall bias); inability to assess impact of caffeine; not easily generalizable (subjects were mainly middle-class Caucasians); no information on additives other than milk; conclusions based on a single follow-up OGTT.
Of note: Only 12 subjects drank decaffeinated coffee exclusively, so separate analysis was not possible; the prevalence of DM in the United States increased three-fold between 1990 and 1999 (almost 7% of the U.S. population is believed to have DM), and global prevalence of DM is expected to almost double by 2030; based on 1999 WHO criteria, subjects in the trial were classified as having Type 2 DM if results of their OGTT were fasting glucose level ≥ 7.0 mmol/L, if post-challenge glucose was ≥ 11.1. mmol/L, if a clinical diagnosis of DM had been made, or if the subject was being treated for DM; 85% of participants reported physical activity three times a week, 44% were hypertensive at baseline, while more than half drank 1-2 alcoholic beverages per day; current coffee drinkers were significantly more likely to report they were also current smokers; in this study, those who were obese or hypertensive, as well as those who either did not drink alcohol or who had three or more alcoholic beverages/d, were more likely to develop DM; most U.S. coffee is made using arabica beans, which contain about 50% of the caffeine found in the robusta coffee beans that are primarily used in Europe.
We knew that: More than half of all U.S. adults drink coffee daily; cohort studies suggest that coffee drinking, whether caffeinated or decaffeinated, confers a protective effect against subsequent development of DM; results of small, placebo-controlled trials suggest that coffee can contribute to insulin resistance and increase blood glucose levels; diterpene content (reportedly associated with increased serum cholesterol levels and higher risk of cardiovascular disease) is significantly lower in drip-filtered coffee; besides caffeine, coffee also contains chlorogenic acid, quinides, and trigonelline.
Comments: It's been easy for this reviewer to comment on articles suggesting possible downsides to drinking coffee—I prefer tea. Of late, however, a spate of articles touting the health benefits of coffee have appeared, including potential improvements in memory and the relief of muscle pain after exercise. Add the current article to the list—but this study should be kept in mind if for no other reason than the benefit suggested by the results for people who already have IGT. Data are beginning to accumulate that compounds within coffee, apart from caffeine, appear to offer a preventive action against development of DM. Is the answer to preventing DM simply to get more of our patients to drink coffee regularly? Obviously not, just as drinking green tea by itself is unlikely to impact cancer incidence in those of us who eat unhealthily and forget to exercise. But the results are intriguing, even to a tea drinker.
What to do with this article: Keep a hard copy in your file cabinet.
Greenfield RH. Male and frail: Angdrogen supplementation? Altern Med Alert 2007;10(3):34-35. Greenfield RH. "Coffee no sugar"--Coffee and IGT. Altern Med Alert 2007;10(3):35-36.Subscribe Now for Access
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