Twenty-nine patients with hypertriglyceridemia (type IV hyperlipoproteinemia) or elevations of both LDL-cholesterol and triglyceride levels (type IIB hyperlipoproteinemia) and 3 patients with an isolated reduction of HDL cholesterol were randomly assigned to receive, in double-blind fashion, pantethine (300 mg 3 times a day) or placebo for 8 weeks, and then the alternate treatment for an additional 8 weeks. In type IIB patients, pantethine lowered total serum cholesterol and LDL cholesterol by 13.5% and increased HDL cholesterol by 10%. Pantethine did not increase HDL cholesterol in type IV patients or in those with an isolated reduction of HDL. In both type IIB and type IV patients, plasma triglycerides were reduced by about 30% if pantethine was given first, and by 13.0-17.8% if pantethine was given after placebo.

Comment: Pantethine is the stable disulfide form of pantetheine, which is a metabolite of pantothenic acid and a major component and precursor of coenzyme A. Numerous studies have shown that pantethine can lower LDL-cholesterol and triglyceride levels and increase HDL-cholesterol levels. Although the lipid-lowering effect of pantethine is not as pronounced as that of statin drugs, it is non-toxic and can be used in combination with other nutritional supplements and dietary changes, with the potential for additive or synergistic effects. In addition to its favorable effect on lipid levels, pantethine has been shown to inhibit platelet aggregation.

Other natural substances that can reduce serum cholesterol include niacin, chromium, calcium, policosanol, beta-sitosterol, psyllium, and red yeast rice. Foods that have been shown to lower cholesterol levels include soy, oat bran or whole oats, whole rye, garlic, onion, rice bran oil, grapefruit and apples (sources of pectin), raw carrots, nuts (including walnuts, almonds, pecans, hazelnuts, and macadamia nuts), yogurt, high-chromium brewer’s yeast, and alfalfa sprouts.

Gaddi A, et al. Controlled evaluation of pantethine, a natural hypolipidemic compound, in patients with different forms of hyperlipoproteinemia. Atherosclerosis 1984;50:73-83.

Five patients (aged 28-54 years) with ulcerative proctitis or proctosigmoiditis, who had complained of symptoms for 1-32 years, received 550 mg of curcumin twice a day for 1 month, and then 550 mg 3 times a day for 1 month. All five patients improved, with reductions in concomitant medication use in four. The improvement in Global score ranged from 15% to 75%. Five patients with Crohn's disease received 360 mg of curcumin 3 times a day for 1 month and then 360 mg 4 times a day for 2 months. Four of five patients improved, as demonstrated by decreases in Crohn's Disease Activity Index scores of 12.9-44% and reductions in sedimentation rates of 17-71%.

Comment: Curcumin is a component of the common spice, turmeric. Animal studies have demonstrated an anti-inflammatory effect of curcumin, and an uncontrolled trial in humans suggested that it might be beneficial in the treatment of rheumatoid arthritis. The results of the present study suggest that curcumin may also be an effective treatment for inflammatory bowel disease. A larger, placebo-controlled trial would be worthwhile.

Holt PR, Katz S, Kirshoff R. Curcumin therapy in inflammatory bowel disease: a pilot study. Dig Dis Sci 2005;50:2191-2193.

One hundred-twenty men (mean age, 66 years) with symptoms of androgen decline (decreased libido and erectile quality, depressed mood, decreased cognitive function, and fatigue) and a low free-testosterone concentration were randomly assigned to receive, in double-blind fashion, either 1) testosterone undecanoate (160 mg/day orally), 2) 2 g/day each of propionyl-L-carnitine and acetyl-L-carnitine (carnitines group), or 3) placebo for 6 months. Erectile function, as determined by the International Index of Erectile Function (IIEF) score, increased (improved) from a mean of 8 in each group at baseline to 16 in the testosterone group, 24 in the carnitines group, and 9 in the placebo group. The increase in IIEF score was significantly greater in the carnitines group than in the testosterone group. Carnitines and testosterone were effective for as long as they were administered, but symptoms recurred when treatment was discontinued.

Comment: Propionyl-L-carnitine is a carnitine derivative that has been found to have greater affinity than L-carnitine for certain tissues and is apparently hydrolyzed to release free L-carnitine in those tissues. L-Carnitine plays a role in energy production by facilitating the transport of fatty acids into mitochondria. Acetyl-L-carnitine functions as a neurotransmitter, with activity similar to that of acetylcholine. The results of the present study indicate that the combination of propionyl-L-carnitine and acetyl-L-carnitine was significantly more effective than testosterone in the treatment of erectile dysfunction associated with age-related androgen decline. The mechanism of action is not clear.

Cavallini G, et al. Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Urology 2004;63:641-646.

Seven herbal products marketed for the treatment of erectile dysfunction were purchased via the Internet (n = 6) or at a local health food store (n = 1). Specimens were analyzed by high performance liquid chromatography and mass spectrometry to detect the presence of sildenafil (Viagra), tadalafil (Cialis) or vardenafil (Levitra). Of the 7 products tested, 1 contained a pharmacological dose of sildenafil (30 mg) and 1 contained a pharmacological dose of tadalafil (20 mg). It was not stated whether the product obtained from the health food store was one of the adulterated products.

Comment: This study indicates that some herbal products sold via the Internet for erectile dysfunction (ED) are adulterated with prescription ED drugs. While true herbal ED products are relatively safe, sildenafil and tadalafil can cause serious adverse reactions in people with cardiovascular disease. In addition, these drugs can interact with a wide range of other prescription medications, and have caused hypotension, shock, or death when used in combination with nitrates. There are many legitimate herbal products on the market, including ones promoted for ED. It would be prudent, however, to avoid purchasing such products from the Internet, unless they are being sold by a company that has been in business for a long time and has an established reputation for selling high-quality products.

Fleshner N, Harvey M, Adomat H, et al. Evidence for contamination of herbal erectile dysfunction products with phosphodiesterase type 5 inhibitors. J Urol 2005;174:636-641.

Forty patients (mean age, 27 years) with irritable bowel syndrome and sleep disturbances were randomly assigned to receive, in double-blind fashion, 3 mg of melatonin or placebo at bedtime for 2 weeks. Compared with placebo, melatonin significantly decreased the mean abdominal pain score (p < 0.001) and increased the mean rectal pain threshold (p < 0.01). Bloating, stool type, stool frequency, anxiety, depression, and sleep patterns were not affected by melatonin.

Comment: In addition to being synthesized by the pineal gland, melatonin is produced in the gastrointestinal tract, where it is involved in the regulation of gastrointestinal motility and sensation. The results of the present study demonstrate that supplementation with 3 mg of melatonin at bedtime for 2 weeks can reduce abdominal pain and rectal pain sensitivity in people with irritable bowel syndrome. The beneficial effects of melatonin on abdominal pain were independent of its action on sleep disturbances.

Song GH, et al. Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study. Gut 2005;54:1402-1407.

Six children with autistic spectrum disorders and persistent diarrhea for many years received 500 mg/day of glucosamine spread over the morning and evening meal for 30 days. The children were already being managed with interventions such as avoidance of dairy products and gluten, and use of probiotics and nutritional supplements; these interventions remained unchanged during the trial. In 5 of the 6 children, diarrhea disappeared during glucosamine supplementation.

Comment: Many autistic children appear to have food sensitivities, which can adversely affect gastrointestinal and brain function. Gluten contains a lectin that is believed to be incompletely broken down in the gut to release an enkephalin-like peptide, which appears to be associated with behavioral and gut disorders in some autistic children. N-acetylglucosamine can block wheat lectin, which led the investigator to consider the possibility that glucosamine would have a similar effect.

Although there was no control group, the results seem impressive, since the children had long-standing diarrhea that had not been controlled by other interventions. The beneficial effect of glucosamine does not seem to be attributable to an interference with wheat lectin, because the children were already avoiding gluten-containing foods. It is possible that glucosamine inhibits the effect of other food-derived peptides or lectins on the gastrointestinal tract.

Danczak E. Glucosamine and plant lectins in autistic spectrum disorders: an initial report on 6 children with uncontrolled diarrhoea. J Nutr Environ Med 2004;14:327-330.

Some 5,141 men (mean age, 51.3 years) were randomly assigned to receive daily a placebo or the combination of vitamin C 120 mg, vitamin E 30 mg, beta-carotene 6 mg, selenium 100 mcg, and zinc 20 mg for 8 years. During the study, 103 cases of prostate cancer were diagnosed. Overall, there was a nonsignificant 12% reduction in prostate cancer incidence associated with nutrient supplementation (relative risk [RR] = 0.88; 95% CI, 0.60-1.29). However, the effect differed significantly between men with a normal baseline prostate-specific antigen (PSA) level (< 3 mcg/L) and those with elevated PSA. Among men with normal PSA, there was a statistically significant 48% reduction in the incidence of prostate cancer in the supplemented group (RR = 0.52; 95% CI, 0.29-0.92). In men with elevated PSA at baseline (less than 10% of the total study group), supplementation was associated with an increased incidence of prostate cancer of borderline statistical significance (RR = 1.54; 95% CI, 0.87-2.72). Supplementation had no effect on PSA levels.

Comment: This study found that modest doses of vitamins C and E, beta-carotene, selenium, and zinc can substantially reduce the risk of prostate cancer in men with an initially normal PSA level. These results support the findings of a previous double-blind study, in which supplementation with 200 mcg/day of selenium from high-selenium yeast for 4.5 years reduced the incidence of prostate cancer by 63%. The possibility that nutritional supplementation increases the risk of prostate cancer in men with an initially elevated PSA level is cause for concern. However, the increase was not statistically significant, and may have been due to chance.

Moreover, better results might have been achieved if the supplement had been formulated slightly differently. The supplement used in the present study did not contain copper, a nutrient that enhances immune function and might conceivably help prevent cancer. Long-term administration of 20 mg/day of zinc may induce marginal copper deficiency, potentially counterbalancing some of the beneficial effect of the administered nutrients. In addition, beta-carotene promotes the development of lung cancer (and conceivably other types of cancer) in cigarette smokers. A modest dose of pre-formed vitamin A might therefore be preferable to beta-carotene in cigarette smokers.

Meyer F, et al. Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial. Int J Cancer 2005;116:182-186.

Forty-five patients (mean age, 69 years) with coronary heart disease and myocardial ischemia were randomly assigned to receive, in double-blind fashion, 240 ml/day of pomegranate juice or a placebo drink for 3 months. The placebo was a modified sports beverage (contents not specified) that was similar in caloric content, flavor, and color to the pomegranate juice. To measure stress-induced ischemia, participants underwent electrocardiographic-gated myocardial perfusion single-photon emission computed tomographic technetium-99m tetrofosmin scintigraphy at rest and during stress at baseline and 3 months. After 3 months, compared with baseline, the extent of stress-induced ischemia decreased by 17.8% in the pomegranate-juice group, and increased by 20.3% increase in the placebo group. The difference in the change between groups was statistically significant (p < 0.05), but it was not clear whether the improvement in the pomegranate-juice group was significant compared with the baseline value. The mean number of angina episodes decreased by 50% in the pomegranate-juice group and increased by 38% in the placebo group, but this difference was not statistically significant.

Comment: Pomegranate juice contains antioxidants such as polyphenols, tannins, and anthocyanins that may have anti-atherosclerotic properties. In a previous study of patients with carotid atherosclerosis, consumption of 250 ml/day of pomegranate juice decreased intima-media thickness of the common carotid arteries by a mean of 35%, as compared with an increase of 9% in the control group (Clin Nutr 2004;23:423-33). This improvement, which was suggestive of a regression of atherosclerosis, was maintained after a total of 3 years in patients who continued to drink pomegranate juice.

In the new study, pomegranate juice appeared to improve stress-induced myocardial ischemia in patients with coronary heart disease. However, the difference in the change between groups was due in large part to a worsening in the placebo group. It is possible that some component of the sports drink had a deleterious effect on cardiac metabolism. If that were the case, then the true effect of pomegranate juice would have been smaller than that reported, and may not have been statistically significant. Nevertheless, the results are consistent with a beneficial effect of pomegranate juice in patients with coronary heart disease.

Sumner MD, et al. Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease. Am J Cardiol 2005;96:810-814.

By: Alan R. Gaby, M.D.