Nutrition Review
What to Watch: Three Experimental Biology Meeting Reports
by Anthony L. Almada, M.Sc.
Scientists from around the world convene annually for Experimental Biology (EB), formerly known as the Federation of American Societies for Experimental Biology (FASEB), the largest life sciences meeting held to disseminate biological research results. EB is an association of 25 different U.S.-based scientific/ research societies. This year's event was held April 18-22 in Washington, D.C., where more than 6,500 scientific reports were presented.
Unlike studies published in peer-reviewed journals, abstracts presented at EB (and at most other meetings of this type) are unreviewed, and the majority never appear as full-length original articles. Although this does not invalidate the data, they should be interpreted with some reservation. While preliminary, the material presented does offer a glimpse at new research directions and serves as a forecasting tool for new products.
Is Ephedra + Caffeine a Smart Combination?
Despite compelling evidence supporting the safety and effectiveness of synthetic ephedrine/caffeine (E+C) combination products as weight-loss and body-fat reduction aids, no studies have examined whether plant-derived E+C combinations have similar effects. Numerous studies ranging in length from weeks to more than a year have documented the safety and tolerability of synthetic E+C products.1,2 However, recent anecdotal reports submitted to the FDA's Medwatch database of adverse reactions to ephedrine and both types of E+C products have cast a regulatory cloud over this product category despite the bias of these types of reports.
One study, the first to explore the tolerability and efficacy of botanical E+C, also raises the question of whether the active constituents of ephedra and guarana may affect tolerability. Obesity researcher Steven Heymsfield, M.D., who last year concluded that Garcinia cambogia extracts had no effect on weight and fat loss when used in conjunction with a high-fiber diet,3 presented data on the effects of a proprietary plant-derived E+C product. In a double-blind, randomized study, 67 weight-stable but obese subjects received, in divided doses, either placebo or a commercially available diet product that contained 72 mg of ephedrine (from Ephedra sinica, ma huang) and 240 mg of caffeine from guarana (Paullinia cupana) for eight weeks. Twenty-four subjects taking E+C completed the eight-week study and lost, on average, nearly five times more weight (-8.7 pounds vs. ±1.8 pounds) and four times more body fat (-2.5 percent vs. +1.5 percent) than placebo.
E+C subjects experienced a greater frequency of adverse effects including constipation, dry mouth, heart palpitations and increased blood pressure. The authors concluded: "[This product] promotes weight loss but may also produce undesirable side effects in some subjects. Safety for long-term use requires further study."
Clinical trials conducted with synthetic E+C mixtures employed longer periods of supplementation and higher doses, yet almost uniformly reported far greater tolerability at eight weeks of use, and reports of decreased blood pressure.4 Previous studies with synthetic forms of E+C have also suggested that the most effective and well-tolerated combination of ephedrine and caffeine is a 1:10 ratio.5
Androstenedione Effects Still Unclear
Do testosterone precursors exert testosteronelike effects? Androstenedione products are often compared to anabolic steroids and testosterone despite the absence of any human or animal data indicating oral ingestion of these hormones has any effect whatsoever—good or bad.
One of the premier protein metabolism laboratories in the world, led by Bob Wolfe, Ph.D., at the University of Texas Medical Branch/Shriners Burn Institute in Galveston, undertook a nonblinded study examining the effects of 100 mg/day of androstenedione, administered in single doses for five days to six young men. Despite finding an increase of androstenedione in the subjects' blood, researchers did not find elevated blood levels of testosterone. Instead they found a significant increase of estradiol in the subjects' blood. Estradiol is the most biologically active estrogen—a "female" hormone. Androstenedione had no effect on leg muscle protein synthesis, an indicator of muscle-protein buildup, but it did increase muscle-protein what many expected. These preliminary observations suggest that androstenedione may have undesirable effects. And these data run counter to other findings that showed androstenedione variably increased blood testosterone after a single dose.6
Wolfe's study, however, is the first to examine androstenedione's measurable effects, such as body weight or composition, and his results complement those published in the June issue of the Journal of the American Medical Association. The JAMA study's results demonstrated significant increases in blood estradiol and significant decreases in cardioprotective high-density lipoprotein (HDL) cholesterol in 30 men, aged 19 to 29, undergoing a resistance training program while taking 300 mg/day of androstenedione. Additionally, neither strength nor muscle mass improved.7 Other studies using a more mature population are near completion and seem to confirm these findings. They also suggest that androstenedione and its chemical cousin, androstenediol, do not improve sexual function or body composition.
It remains to be seen whether other hormone precursors such as the 19-nor forms can circumvent conversion into estrogens and elude the pathways that lower HDL cholesterol while still increasing strength and muscle mass—safely.
Larch: The New Echinacea?
One of the recognized immune-stimulating components of echinacea (Echinacea spp.) is a class of compounds called arabinogalactans (AG). Another source of AG is the Western larch tree (Larix occidentalis).
Joanne Slavin, Ph.D., and colleagues from the University of Minnesota in St. Paul studied the effects of purified, water-soluble larch extract on both the immune and gastrointestinal systems of 20 healthy people. Supplementation with 15 g/day of larch-derived AG for three weeks led to a statistically significant 14 percent increase in monocytes, a class of white blood cells. A 30 g/day dose produced results that were not statistically significant. It is unclear why the larger dose had less effect. The authors concluded, "These results indicate an enhancement of the mononuclear portion [monocytes in this study] of the human immune system with arabinogalactan supplementation."
Separate analysis of the same study found supplementation with larch AG to be associated with a significant decrease in stool frequency and an increase in stool total anaerobe and lactobacillus species. Anaerobes help increase the acidity of the gut contents and thereby decrease the overgrowth of pathogenic bacteria. Subjects taking 30 g/day first displayed greater numbers of the anaerobic, pathogenic clostridium species bacteria, while those taking 15 g showed a trend for reduced numbers. Although the numbers were not statistically significant, this merits further investigation and also suggests a dose greater than 15 g but less than 30 g is preferable. Researchers also observed a significant increase of lactobacilli in the stools of subjects who received larch AG, indicating a prebiotic effect. The counts were three times the amount before supplementation. The researchers concluded, "AG is well tolerated in subjects and appears to have positive effects on fecal chemistry."
Echinacea's rich history of use and existing body of research will likely keep it the herbal immune-response modifier. But to its credit, larch AG has a multipurpose profile. It is a prebiotic, a soluble fiber source and an immune-response modifier, plus it is less expensive than echinacea. Researchers must now explore whether the effects of larch AG translate to therapeutic or preventive activity in conditions such as traveler's and antibiotic-associated diarrhea, chronic viral infections and acute infections such as colds and flu.
Anthony L. Almada, M.Sc. a nutritional/ exercise biochemist, was co-founder of Experimental and Applied Sciences Inc. (EAS) in Golden, Colo. He now leads IMAGINutrition and MetaResponse Sciences in Aptos, Calif.
References
1. Earnest CP, et al. Oral 4-androstene-3,17-dione and 4-androstene-3,17-diol supplementation in young males. JPEN 1999;23(1):S62.
2. King DS, et al. Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men. JAMA 1999 Jun 2;281(21):2020-8.
3. Toubro S, et al. Safety and efficacy of long-term treatment with ephedrine, caffeine and an ephedrine caffeine mixture. Int J Obesity 1993;17(S1):S69-S72.
4. Breum L, et al. Comparison of an ephedrine caffeine combination and dexfenfluramine in the treatment of obesity—a double-blind multi-centre trial in general practice. Int J Obesity 1994;18(2):99-103.
5. Heymsfield SB, et al. Garcinia cambogia (hydroxycitric acid) as a potential anti-obesity agent: a randomized controlled trial. JAMA 1998 Nov 11;280(11):1596-600.
6. Astrup A, et al. The effect and safety of an ephedrine caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet—a double blind trial. Int J Obesity 1992;16(4):269-77.
7. Astrup A, et al. Thermogenic synergism between ephedrine and caffeine in healthy volunteers—a double-blind, placebo-controlled study. Metabolism 1991;40(3):323-9.
