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LITERATURE REVIEW AND COMMENT
by Alan R. Gaby, M.D.

 

Cow's milk and constipation

Sixty-five children (aged 11-72 months) with chronic constipation (defined as having one bowel movement every 3-15 days) who had failed to respond to laxatives received, in double-blind fashion, cow's milk or soy milk for two weeks. After a one-week washout period, the feedings were reversed for an additional two weeks. Forty-four of the 65 children (68%) had a resolution of constipation while receiving soy milk. Anal fissures and pain with defecation also resolved in patients who suffered from these problems. In contrast, none of the patients showed a positive response while receiving cow's milk. Children who improved had a higher frequency of coexistent rhinitis, dermatitis or bronchospasm, compared with children who did not improve (11 of 44 vs 1 of 21; p = 0.05).

COMMENT: This study strongly suggests that intolerance to cow's milk is a common cause of chronic constipation, as well as anal fissures and pain on defecation, in young children. In an editorial accompanying this report, it was suggested that a diet free of cow's-milk protein should be considered for children with chronic constipation who do not respond to laxatives. This reporter would respectfully venture to suggest that a more appropriate recommendation would be to consider laxatives in patients who do not respond to avoidance of cow's milk or to other natural remedies.

Iacono G, et al. Intolerance of cow's milk and chronic constipation in children. N Engl J Med 1998;339:1100-1104.

Vitamin E for hepatitis B

Twenty-four patients with chronic hepatitis B (19 of whom had failed to respond to interferon-alpha) were randomly assigned to receive vitamin E (300 mg twice daily) for three months or no treatment. The patients were followed monthly for nine months. Four patients receiving vitamin E discontinued treatment because of marked increases in ALT levels. A similar increase in ALT levels was seen in two control patients. Five (41.7%) of the 12 patients receiving vitamin E had a complete response, defined as normalization of ALT levels and clearance of hepatitis B virus DNA from the serum. Three of the five patients with a complete response had not responded to previous interferon-alpha treatment. None of the patients in the control group had a complete response. No side effects were seen.

COMMENT: The results of this small pilot study suggest that vitamin E is of value in the treatment of chronic hepatitis B. Although the mechanism of action is not known, vitamin E does have some hepatoprotective effects and may also enhance immune function. A larger, placebo-controlled study is needed to confirm this report; however, vitamin E is inexpensive and safe and could reasonably be included as part of the treatment regimen for patients with hepatitis B.

Andreone P, et al. Vitamin E for chronic hepatitis B. Ann Intern Med 1998;128:156-157.

Vitamin D deficiency

Of 290 consecutive hospital inpatients on a general medical ward, 57% were found to be deficient in vitamin D (serum concentration of 25-hydroxyvitamin D of 15 ng/ml or lower) and 22% were considered severely deficient (serum concentration of 25-hydroxyvitamin D less than 8 ng/ml). Significant predictors of vitamin D deficiency were low vitamin D intake, less exposure to ultraviolet light, anticonvulsant-drug therapy, renal dialysis, nephrotic syndrome, hypertension, diabetes mellitus, and winter season. Of patients who consumed more than the RDA for vitamin D, 43% were found to be deficient in the vitamin.

COMMENT: This study demonstrates that vitamin D deficiency is extremely common among general medical inpatients, even among those whose vitamin D intakes exceed the RDA. Vitamin D deficiency can result in osteoporosis or osteomalacia and may also contribute to the development of cancer. Individuals who are risk of developing vitamin D deficiency should have their vitamin D status assessed or should be supplemented empirically with vitamin D and/or sunlight.

Thomas MK, et al. Hypovitaminosis D in medical inpatients. N Engl J Med 1998;338:777-783.

Treatment with hydrochloric acid

Gastric analysis with histamine stimulation was performed on 40 patients with chronic urticaria. Approximately 65% of the patients had either hypochlorhydria or achlorhydria. Of the patients with reduced acid output, 65% obtained almost complete or partial relief of symptoms with hydrochloric acid (HCl) therapy. These patients previously had been unresponsive to all other forms of treatment. The best results were obtained in the 22 patients with achlorhydria. In this group, 18 patients (82%) were almost completely relieved by HCl therapy. In another report, administration of dilute HCl altered the putrefactive flora ordinarily present in the small intestine of achlorhydric individuals.

According to the second report, therapeutic use of dilute HCl has fallen into disrepute, largely on theoretical grounds. However, many capable internists and dermatologists remain convinced, on the basis of clinical experience, that acid therapy is beneficial.

COMMENT: These reports from 50 years ago have been revived in order to remind practitioners that hypochlorhydria is common and that administration of HCl may be helpful for many patients. Inadequate secretion of HCl can result in malabsorption of protein, vitamins and minerals, and can facilitate the overgrowth of microorganisms in the stomach or small intestine. Gastric analysis by radiotelemetry is a fairly reliable method of diagnosing hypochlorhydria. If diagnostic testing is not available, a trial (under medical supervision) of low-dose betaine hydrochloride (such as 10-30 grains per meal) may be considered for individuals with bloating after meals, poor digestion, weak fingernails, rosacea, refractory iron deficiency, or other problems that are associated with hypochlorhydria. People who are taking hydrochloric acid should not use ulcer-inducing drugs such as aspirin (or other non-steroidal anti-inflammatory drugs) or alcohol.

Rawls WB, Ancona VC. Chronic urticaria associated with hypochlorhydria or achlorhydria. Rev Gastroenterol 1951;18:267.

Anonymous. A plug for acid therapy. Am J Dig Dis 1948;16:418.

Victor Herbert is still fighting

A landmark prospective, double-blind study was published two years ago in JAMA (1996;276:1957-1963), demonstrating that supplementation with 200 mcg/day of selenium (in the form of high-selenium brewer's yeast) reduced the incidence of prostate, colorectal and lung cancer, and reduced overall cancer mortality by 50%. A few months after the article was published, a letter appeared in JAMA from Dr. Victor Herbert, a well known critic of alternative medicine. Dr. Herbert pointed out that, while selenium supplementation significantly reduced cancer mortality, it did not significantly reduce all-cause mortality. According to Herbert, that means that selenium increased mortality from diseases other than cancer, and that selenium supplements may therefore be harmful to certain individuals.

COMMENT: While there were, in fact a few more non-cancer deaths in the selenium group than in the placebo group, the total death rate (from all causes) was 17% lower in the selenium group than in the placebo group. Although that difference was not statistically significant (p = 0.14), it was relatively large. When elderly individuals are followed up for more than 6 years (as in the selenium study), some will die during the follow-up period. If treatment with selenium helped prevent the development of cancer, then an individual whose time is up will likely succumb to another disease. However, that does not mean that taking selenium increased that person's susceptibility to the other disease. While Dr. Herbert may continue to search for a subgroup of individuals who will be harmed by administration of 200 mcg/day of selenium, I'll take my 17% reduction in overall mortality every morning along with my high-selenium brewer's yeast.

Herbert V. Selenium supplementation and cancer rates. JAMA 1997;277:880

Chemotherapy side effect: still in the dark (ages)

The cardiac toxicity of doxorubicin (adriamycin), a drug used to treat cancer, was discussed in a recent review article in the New England Journal of Medicine (1998;339:900-905). This drug can cause severe and often irreversible cardiomyopathy. While various strategies for prevention and treatment of cardiac toxicity have been tried, none are particularly effective. Conspicuously absent from the report was any mention of coenzyme Q10.

COMMENT: There is evidence that adriamycin may induce cardiotoxicity by inhibiting coenzyme Q10-dependent enzymes. Pretreatment of mice for four days with coenzyme Q10 (10 mg per kg intraperitoneally) reduced the death rate from acute administration of adriamycin.

In a pilot study, seven patients received coenzyme Q10 (100 mg per day), beginning three to five days before adriamycin treatment, while another seven patients (controls) received adriamycin alone. Cardiac function (as determined by heart rate, stroke index, cardiac index and ejection fraction) deteriorated significantly in the control group. Coenzyme Q10-treated patients, on the other hand, showed little or no cardiotoxicity, even though their cumulative adriamycin dose was 50% greater than that of the controls. Despite the preliminary nature of this study, prophylactic administration of coenzyme Q10 seems warranted, considering the seriousness of adriamycin toxicity and the safety and relatively low cost of coenzyme Q10.

Combs AB, et al. Reduction by coenzyme Q10 of the acute toxicity of adriamycin in mice. Res Commun Chem Pathol Pharmacol 1977;18:565-568.

Judy WV, et al. Coenzyme Q10 reduction of adriamycin cardiotoxicity. In Folkers K, Yamamura Y (eds.). Biomedical and Clinical Aspects of Coenzyme Q, vol. 4, Elsevier Publ., 1984, pp. 231-241.

Therapeutic touch does work

In a single-blind randomized trial, 25 patients with osteoarthritis of the knee received either therapeutic touch, mock therapeutic touch or standard care. The main outcome measures were pain, general well-being and health status (as determined by standardized assessment criteria). The patients receiving therapeutic touch had significantly decreased pain and improved function, as compared with the patients receiving mock therapeutic touch or standard care.

COMMENT: A recent report published in JAMA purported to "debunk" claims that therapeutic touch is of value. However, the JAMA study did not really assess the effectiveness of therapeutic touch. Rather, it tested the ability of certain individuals to detect a human "energy field."

Double-blind trials are extremely difficult (if not impossible) to perform when the treatment being studied is influenced by the person administering it. An alternative method of studying such treatments is the "n of 1" trial, in which a patient with a condition that is chronic and stable alternately receives treatment and no treatment. "N of 1" trials are considered acceptable, as long as a single intervention is being tested and the probability of spontaneous improvement occurring is very low. The more "good anecdotes" we submit to medical journals, the sooner alternative medicine will find its way into the mainstream.

Gordon A, et al. The effects of therapeutic touch on patients with osteoarthritis of the knee. J Fam Pract 1998;47:271-277.

Folic acid and cancer

To evaluate the relation between folate intake and incidence of colon cancer, a prospective cohort study was performed on 88,756 women participating in the Nurses' Health Study who were free of colon cancer in 1980 and provided information about diet and multivitamin use from 1980 to 1994. During the follow-up period 442 new cases of colon cancer were diagnosed. After controlling for age, family history, and intake of meat, alcohol and fiber, intake of more than 400 mcg/day of folate was associated with a 31% lower incidence of colon cancer, compared with intake of 200 mcg/day or less. Further controlling for intake of vitamins A, C, E and calcium did not significantly change the results. Use of a folate-containing multivitamin for more than 15 years was associated with a 75% reduction in colon cancer risk, whereas shorter-term use of multivitamins was not associated with significantly lower risk. Folate from dietary sources alone was related to a modest reduction in risk of colon cancer.

COMMENT: This study suggests that long-term use of a multivitamin supplement may substantially reduce the risk of developing colon cancer and that this effect may be due largely to the folic acid. It is likely that other nutrients present in multivitamins and in high-folate foods (such as vitamin C and vitamin E) also exert a protective effect. One cannot rule out the possibility of selection bias in the present study (i.e., people who take supplements probably take generally better care of themselves). However, the results are consistent with previous studies demonstrating an anticancer effect of folate. Although additional studies need to be done, eating a high-quality diet and taking a multivitamin seems like a good insurance policy.

Giovannucci E, et al. Multivitamin use, folate, and colon cancer in women in the nurses' health study. Ann Intern Med 1998;129:517-524.

 


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