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From the Townsend Letter
July 2010

Literature Review & Commentary
by Alan R. Gaby, MD

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Vitamin A and Intestinal Parasites
Seventy-nine children (mean age, 3.5 years) living in an impoverished urban area in Brazil where vitamin A deficiency is prevalent were randomly assigned to receive, in double-blind fashion, a single dose of vitamin A (100,000 IU for children less than 12 months of age; 200,000 IU for older children) or placebo. One month after treatment, the proportion of children who had a new parasitic infestation was significantly lower in the vitamin A group than in the placebo group (20% vs. 31%; p < 0.05). The beneficial effect was due primarily to fewer Giardia lamblia infections.

Comment: Vitamin A plays a role in immune function and has been found to protect against various types of infection. The results of the present study indicate that maintaining adequate vitamin A status improves host defenses against parasitic infestations, particularly Giardia. It is of interest that vitamin A absorption is impaired in people with giardiasis. Thus, Giardia, like politicians, attempts to create conditions favorable to its survival.

Lima AAM et al. Effects of vitamin A supplementation on intestinal barrier function, growth, total parasitic, and specific Giardia spp infections in Brazilian children: a prospective randomized, double-blind, placebo-controlled trial. J Pediatr Gastroenterol Nutr. 2010;50:309–315.

Papaya Seeds Eradicate Parasites
Sixty asymptomatic Nigerian children with evidence of intestinal parasites on stool microscopic examination were randomly assigned to receive 20 ml of an elixir containing honey and air-dried and blended Carica papaya (papaya) seeds (4 g of seeds per 20 ml) or honey alone (placebo). Seven days after treatment, stool examination was negative for parasites in 77% of the children receiving active treatment and in 17% of those receiving placebo (p < 0.00002). No adverse effects were seen. The stool clearance rates for the various types of parasites were 71%–100% (Ascaris lumbricoides [11 of 13], Entamoeba histolytica [5 of 7], Necator americanus [4 of 5], Strongyloides stercoralis [4 of 4], Trichuris trichiura [3 of 3], Giardia lamblia [2 of 2], and Taenia saginata [1 of 1]).

Comment: Seeds of the papaya fruit have antihelminthic and antiamoebic activities, and have been used in folk medicine to treat helminthiasis. The results of the present study suggest that papaya seeds have broad-spectrum activity against intestinal parasites, and that treatment according to the protocol described above is a viable alternative to conventional therapy.

Okeniyi JAO et al. Effectiveness of dried Carica papaya seeds against human intestinal parasitosis: a pilot study. J Med Food. 2007;10:194–196.

Digestive Enzymes for Functional Dyspepsia
One hundred fifty-one Chinese patients (mean age, 45 years) with functional dyspepsia were randomly assigned to receive, in double-blind fashion, Combizym (2 tablets 3 times per day after meals) or placebo for two weeks. After a one-week washout period, each patient received the alternate treatment for an additional two weeks. Combizym contains 220 mg of pancreatin and 24 mg Aspergillus oryzae enzyme extract. The mean severity of dyspepsia symptoms compared with baseline decreased by 65% with active treatment and by 8% with placebo (p < 0.01 for the difference in the change between groups). Symptoms that improved with active treatment included abdominal distension, belching, diarrhea, abdominal pain, and epigastric burning.

Comment: It is concluded that this enzyme preparation was effective in the treatment of dyspepsia.

Ran ZH et al. The efficacy of Combizym in the treatment of Chinese patients with dyspepsia: a multicenter, randomized, placebo-controlled and cross-over study: Shanghai Combizym Clinical Cooperative Group. J Dig Dis. 2009;10:41–48.

Vitamin C Enhances Helicobacter Pylori Eradication
Three hundred twelve patients with Helicobacter pylori infection were randomly assigned to receive amoxicillin (500 mg twice a day), metronidazole (500 mg twice a day), bismuth (240 mg twice a day), and omeprazole (20 mg twice a day) for two weeks or the same regimen plus 500 mg per day of vitamin C. In intent-to-treat analysis, the eradication rate four weeks after the end of treatment (as determined by a urea breath test) was significantly higher in the group that received vitamin C (78% vs. 49%; p < 0.0001).

Comment: Vitamin C has been found to inhibit the growth of H. pylori in vitro, and preliminary research suggests that it may also be effective in vivo. The results of the present study indicate that supplementation with a moderate dose of vitamin C significantly increased the H. pylori eradication rate in patients receiving conventional antimicrobial therapy. In another study, the addition of 500 mg/day of vitamin C to conventional therapy allowed for a reduction in the dose of clarithromycin, while preserving or enhancing the efficacy of the treatment.

Zojaji H et al. The efficacy of Helicobacter pylori eradication regimen with and without vitamin C supplementation. Dig Liver Dis. 2009;41:644–647.

Magnesium Orotate for Heart Failure
Seventy-nine patients with severe congestive heart failure (New York Heart Association class IV) were randomly assigned to receive, in double-blind fashion, placebo or magnesium orotate (2 g 3 times per day for one month followed by 1 g 3 times per day for 11 months). All patients received conventional therapy. After one year, the mean survival rate was significantly higher in the active-treatment group than in the placebo group (75.7% vs. 51.6%; p < 0.05). Symptoms improved in 38.5% of patients receiving active treatment, but did not improve in any patient receiving placebo (p < 0.01).

Comment: Orotate (orotic acid) is an intermediate in pyrimidine biosynthesis, and has been reported to have cardioprotective effects. In the 1960s and 1970s, Hans Nieper and others promoted magnesium orotate as being effective for the treatment of cardiovascular disease. However, until now there has been little controlled research to investigate that claim. Based on these encouraging results, further research on magnesium orotate is warranted.

Stepura OB, Martynow AI. Magnesium orotate in severe congestive heart failure (MACH). Int J Cardiol. 2009;131:293–295.

Vitamin C Reduces Elevated C-Reactive Protein
Three hundred ninety-six healthy nonsmokers (mean age, 44 years) were randomly assigned to receive, in double-blind fashion, 1,000 mg per day of vitamin C, 800 IU per day of vitamin E, or placebo for two months. The median C-reactive protein (CRP) level at baseline was relatively low (0.85 mg/L). Compared with placebo, neither vitamin C nor vitamin E had an effect on CRP levels. However, among participants with CRP levels indicative of increased cardiovascular disease risk (≥ 1 mg/L), compared with placebo, vitamin C decreased the median CRP level by 25.3% (p = 0.02), a reduction similar to that seen with statins. The effect of vitamin E was not significant.

Comment: An elevated CRP level is an independent risk factor for cardiovascular disease. By decreasing elevated CRP levels, vitamin C supplementation may help prevent heart disease. Other cardioprotective effects of vitamin C include inhibition of platelet aggregation and reduction of elevated systolic blood pressure. In addition, vitamin C enhances tissue integrity, and might therefore increase the resistance of endothelial tissue against various types of injury that initiate the process of atherosclerosis. Ensuring adequate vitamin C intake seems to be an important component of a heart disease prevention program.

Block G et al. Vitamin C treatment reduces elevated C-reactive protein. Free Radic Biol Med. 2009;46:70–77.

Vitamin D May Help Prevent Tissue Rejection After Liver Transplant
One hundred thirty-three patients who had received a liver transplant were studied. The median pretransplant serum 25-hydroxyvitamin D concentration was 12.5 ng/ml (31.25 nmol/L). Forty patients had concentrations ≤12.5 ng/ml, of whom 6 had a level ≤5.0 ng/ml. Seventy-nine patients received a vitamin D3 supplement to treat post­transplant osteoporosis. During the two months after the transplant, moderate-to-severe acute rejection episodes were independently associated with lower pretransplant serum 25-hydroxyvitamin D concentrations (p < 0.02). Early vitamin D supplementation (within the first month after the transplant) was independently associated with a lower incidence of acute rejection episodes (p < 0.05).

Comment: Vitamin D deficiency is common in patients undergoing liver transplantation, possibly because of impaired hepatic conversion of vitamin D to 25-hydroxyvitamin D. Since vitamin D modulates immune function, it is theoretically possible that vitamin D supplementation could promote organ rejection in patients who have received a transplant. However, the results of the present study suggest that opposite: that vitamin D deficiency increases the risk of organ rejection and that maintaining adequate vitamin D status prevents rejection.

Bitetto D et al. Vitamin D and the risk of acute allograft rejection following human liver transplantation. Liver Int. Epub 2009 Oct 22.

Oral Zinc for Warts
Fifty-five patients (aged 8–27 years) with multiple warts that had failed to respond to conventional therapy were random­ly assigned to receive, in double-blind fashion, zinc sulfate or placebo for at least one month and for a maximum of two months. The dosage of zinc sulfate was 10 mg/kg of body weight per day, to a maximum of 600 mg per day (136 mg per day of elemental zinc). Of the 32 patients in the zinc group, 19 (59%) had a complete resolution of warts after one month, and an additional 6 had a complete response after two months of treatment (total response rate, 78%). Among the patients who responded to zinc, none had a recurrence during a six-month follow-up period. Of the 23 patients in the placebo group, one had a complete reso­lution of warts after one month and two others had a com­plete response after two months (total response rate, 13%).

Comment: Warts are benign epidermal tumors caused by human papilloma viruses. Zinc enhances immune function and also has antiviral activity, effects that may be useful in the treatment of warts. The results of the present study confirm a previous report indicating that oral zinc is an effective treatment for warts. The high doses of zinc that were used in this study frequently cause side effects such as nausea, vomiting, and epigastric pain. Zinc picolinate and zinc citrate appear to be better absorbed than zinc sulfate. It is therefore possible that warts could be effectively treated with lower (and better tolerated) doses of these other zinc preparations.

Yaghoobi R et al. Evaluation of oral zinc sulfate effect on recalcitrant multiple viral warts: a randomized placebo-controlled clinical trial. J Am Acad Dermatol. 2009;60:706–708.

Alan R. Gaby, MD


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