Clinical Briefs
Oral L-Arginine for Interstitial Cystitis
September 1999; Volume 2: 107
Source: Korting GE, et al. A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis. J Urol 1999;161:558-565.
Nitric oxide synthase activity is decreased in the urine of patients with interstitial cystitis. In a preliminary trial, oral L-arginine, the substrate for nitric oxide synthase, increased urinary nitric oxide synthase activity and improved interstitial cystitis symptoms.
A total of 53 interstitial cystitis patients were randomly assigned to receive daily 1,500 mg L-arginine or placebo orally for three months. Interstitial cystitis symptoms were assessed by interviews at two weeks, and one, two, and three months. The trial was completed by 21 of 27 patients in the L-arginine group and 25 of 26 in the placebo group. Using per protocol analysis, 6/21 (29%) patients in the L-arginine group and 2/25 (8%) in the placebo group were clinically improved by the end of the trial (P = 0.07). A Likert scale showed greater global improvement in the L-arginine group (10/21, 48%) than in the placebo group (6/25, 24%) at three months (P = 0.05) with a decrease in pain intensity (P= 0.04), and tendency toward improvement in urgency (P = 0.05) and frequency of pain (P = 0.09). Using an intention to treat approach, there were no differences between the groups.
We conclude that oral L-arginine may decrease pain and urgency in a subset of interstitial cystitis patients.
Comment
A successful pilot study with more hands-on attention than their intervention helped these Yale investigators to gain NIH support for this double-blind investigation. Only after three months was there a demonstrable difference between L-arginine and placebo pa-tients. Patients with greater than a 800 cc bladder capacity and a history of recurrent genitourinary infections were the two subgroups that experienced improvement. Adverse effects were not described, although four of the six or seven (per the authors) who withdrew from the arginine group complained of increased pain, not decreased pain.
Oral L-arginine is also touted for nonobstructive coronary disease. (See Alternative Medicine Alert, June 1999, p. 72.) It seems to have beneficial effects, but also "has been reported to activate herpes virus replication and interact, in animal models, with tumor growth."
Recommendation
In patients with interstitial cystitis refractory to standard measures, who are willing to risk actually increased pain, who are not immunosuppressed, and who do not have a history of herpes activation, oral L-arginine may be worth a try. If it does work, it will probably take three months. Be cautious.
Lycopene for Prostate Cancer
September 1999; Volume 2: 107-108
Source: Gann PH, et al. Lower prostate cancer risk in men with elevated plasma lycopene levels: Results of a prospective analysis. Cancer Res 1999;59:1225-1230.
Dietary consumption of the carot-enoid lycopene (mostly from tomato products) has been associated with a lower risk of prostate cancer. We conducted a nested case-control study using plasma samples obtained in 1982 from healthy men enrolled in the Physicians’ Health Study, a randomized, placebo-controlled trial of aspirin and beta-carotene. Subjects included 578 men who developed prostate cancer within 13 years of follow-up and 1,294 age and smoking status-matched controls.
We quantified the five major plasma carotenoid peaks (alpha- and beta- carotene, beta-cryptoxanthin, lutein, and lycopene) plus alpha- and gamma-tocopherol and retinol using high- performance liquid chromatography.
Lycopene was the only antioxidant found at significantly lower mean levels in cases than in matched controls (P = 0.04 for all cases). The odds ratios (OR) for all prostate cancers declined slightly with increasing quintile of plasma lycopene; there was a stronger inverse association of aggressive prostate cancers (5th quintile, OR = 0.56, confidence interval [CI] = 0.34- 0.91). In the placebo group, plasma lycopene was very strongly related to lower prostate cancer risk (5th quintile OR = 0.40; P trend = 0.006 for aggressive cancer), whereas there was no evidence for a trend among those assigned to beta-carotene supplements. However, in the beta-carotene group, prostate cancer risk was reduced in each lycopene quintile relative to men with low lycopene and placebo. The only other notable association was a reduced risk of aggressive cancer with higher alpha-tocopherol levels that was not statistically significant. None of the associations for lycopene were confounded by age, smoking, body mass index, exercise, alcohol, multivitamin use, or plasma total cholesterol level.
A recent prospective dietary analysis noted that for men with low lycopene levels, beta-carotene supplements were associated with risk reductions comparable to those observed with high lycopene levels. Increased consumption of tomato products and other lycopene-containing foods might reduce the occurrence or progression of prostate cancer.
Comment
The print ads showing lycopene pouring from a squeezable bottle are finally giving middle-aged male Cubs fans something to cheer about. The theory is this—if lipid soluble antioxidants like lycopene and other car-otenoids can protect DNA and membrane lipids from oxidation, then fewer neoplasms will result. Lycopene is stored in the prostate and cannot be converted to vitamin A, making it relatively more available in the tissue.
The results from this study of 22,000 physicians hinge on a single baseline plasma sample to characterize long-term levels of circulating lycopene. Higher lycopene levels are associated with lower risk of developing prostate cancer in those men not taking beta-carotene supplements. Men taking beta-carotene did not have a significantly lower risk of developing prostate cancer when compared with men taking placebo. Those men taking beta-carotene who also had high lycopene levels did not get additional protection from them.
Cooked tomato products have more lycopene than fresh or dried tomatoes. Because lycopene is fat-soluble, oil improves its bioavailability. It seems that gently warmed heirloom tomato slices sprinkled with roasted garlic, ribbons of arugula, toasted pine nuts, and extra virgin olive oil really can be good for the old prostate. A recent comprehensive review in the Journal of the National Cancer Institute (1999;91: 317-331) emphasized that purified lycopene supplements have not been tested—only red tomatoes (and pink grapefruit, apricots, and watermelon).
How much is enough to reduce prostate cancer incidence? No one knows—or even if it’s the lycopene that is conferring the benefit. But this food can’t harm, and from these data, it may well help.
Recommendation
Men at risk for prostate cancer cannot hurt themselves by eating more simmered marinara, roasted tomato sauce, or sauteed tomato salsa. Tell men to have some every day—for the flavor.
Supplements for Institutionalized Elderly Patients
September 1999; Volume 2: 108
Source: Girodon F, et al. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: A randomized controlled trial. Arch Intern Med 1999;159:748-754.
Antioxidant supplementation is thought to improve immunity and thereby reduce infectious morbidity. However, few large trials in elderly people have been conducted that include end points for clinical variables. We sought to determine the effects of long-term daily supplementation with trace elements (zinc sulfate and selenium sulfide) or vitamins (beta-carotene, ascorbic acid, and vitamin E) on immunity and the incidence of infections in institutionalized elderly people. We conducted a randomized, double-blind, placebo-controlled intervention study including 725 patients over age 65 (mean age 83.9), institutionalized in 25 geriatric centres in France. Patients received an oral daily supplement of nutritional doses of trace elements or vitamins or a placebo within a 2 x 2 factorial design for two years.
Correction of specific nutrient deficiencies was observed after six months of supplementation and was maintained for their first year, during which there was no effect of any treatment on delayed-type hypersensitivity skin re-sponse. Antibody titers after influenza vaccine were higher in groups that received trace elements alone or with vitamins. The vitamin group had significantly lower antibody titers (P < 0.05). The number of patients without respiratory tract infections during the study was higher in groups that received trace elements (P = 0.06). Supplementation with neither trace elements nor vitamins significantly reduced the incidence of urogenital infections. Survival analysis for the two years did not show any differences between the four groups.
Low-dose supplementation of zinc and selenium provides significant improvement in elderly patients by increasing the humoral response after vaccination and could have considerable public health importance by reducing morbidity from respiratory tract infections.
Comment
These French investigators assessed the prevalence of nutrient deficiency by assessing serum value, and finding approximately 80% of patients to be deficient in selenium. Deficiencies were not significantly different across the groups. Supplemental zinc (20 mg) and selenium (100 mcg) were provided. Except for zinc, serum concentrations of vitamins reached a plateau after six months; zinc levels rose throughout the study, as zinc is absorbed slowly in older people. Adherence was very good—over 85%.
Trace mineral supplementation was associated with fewer respiratory tract infections—markedly so.
Measuring mineral levels is not yet a standard assessment, and for this indication, seems unnecessary. The cost of the needed intervention is small, the side effect profile favorable, and the therapy efficacious. Compared with colds in nursing homes, zinc and selenium supplements look great.
Recommendation
All residents of long-term care institutions over age 65 should take a trace mineral supplement of zinc and selenium, in addition to regular vitamins—about twice the U.S. RDI for vitamin C, beta-carotene, and vitamin E.
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