In a recent issue of the New England Journal of Medicine ( 2004;351:1323-1331), there was a review article on the diagnosis and management of Bell's palsy. In keeping with the tradition of certain major medical journals of either ignoring or misrepresenting the evidence supporting natural therapies, this article did not mention that intramuscular vitamin B12 appears to be an effective treatment.

In a 1959 report, two patients with Bell's palsy of 1.5 and 4 years' duration, respectively, experienced complete or almost complete recovery within 20 days after beginning a series of daily or every-other-day cyanocobalamin injections. More recently, methylcobalamin (500 mcg intramuscularly, 3 times a week) was compared with prednisolone and with the combination of methylcobalamin and prednisolone in a randomized trial. The mean time until complete recovery of facial nerve function was significantly less (p < 0.001) in patients receiving methylcobalamin (1.95 weeks) or methylcobalamin plus prednisolone (2.05 weeks) than in those receiving prednisolone alone (9.60 weeks).

Comment: I sent a letter to NEJM, pointing out the potential importance of this safe and inexpensive alternative to acyclovir and glucocorticoids. While it has been my experience that sending letters to NEJM or JAMA typically results in a polite rejection letter, on rare occasions these journals behave unpredictably and actually publish my letter. So, I keep writing letters, because variable-interval reinforcement is difficult to extinguish, and because if you don't try to promote an attitude shift, you don't have a right to complain. Actually, complaining has gotten to be less fun over the years, but the need to set a dysfunctional healthcare system straight remains.

Mitra M, Nandi AK. Cyanocobalamin in chronic Bell's palsy. J Indian Med Assoc 1959;33:129-31.

Jalaludin MA. Methylcobalamin treatment of Bell's palsy. Methods Find Exp Clin Pharmacol 1995;17:539-44.

Two hundred seventy-seven children (aged 3 years) living on the Isle of Wight, UK, consumed a diet for four weeks that eliminated artificial colorings and benzoate preservatives. During the second week of the diet, the children were randomly assigned to receive, in double-blind fashion, daily challenges with a drink containing either 1) artificial colorings (20 mg/day total; 5 mg/day each of sunset yellow, tartrazine, carmoisine, and ponceau 4R) and sodium benzoate (45 mg/day) or 2) placebo. During the fourth week, the children were challenged daily with the alternate drink.

During the first week (the elimination phase), a significant reduction in hyperactive behavior was observed. In the challenge phase, significantly greater increases in hyperactive behavior were seen with the food additives than with the placebo. These differences were identified by parents’ ratings but not by objective testing in the clinic. The magnitude of the benefit obtained by avoiding food additives was similar to that for clonidine in the treatment of children with ADHD, but was less than that seen with methylphenidate (Ritalin). The effect of the food additives on hyperactive behavior was not influenced by the presence or absence of hyperactivity at baseline, nor by the presence or absence of atopy, as determined by skin prick tests.

Comment: There have been many studies assessing the effects of food additives. While many of these studies demonstrated an adverse effect of food additives, others found little or no effect. Some of the negative studies suffered from design flaws. For example, one study compared the effect of a chocolate cookie containing artificial food dyes to that of a "placebo" chocolate cookie. Some children in that study may have experienced an adverse reaction to the chocolate "placebo", which would have masked any effect of the food dyes. In other studies, children underwent challenges with food dyes after they had been on an additive-free diet for at least three months. Tolerance to allergens tends to increase the longer a person avoids them, so the children in those studies may have lost their sensitivity to the additives by the time they were challenged with them. Moreover, most of the previous studies investigated only artificial colors, not sodium benzoate, which appears to be an important symptom-evoking substance.

The present study demonstrates that commonly used food additives contribute to hyperactive behavior in children, and that the effect of these additives is not influenced by prior levels of hyperactivity or by atopy. An earlier study (Lancet 1985;1:540-545) also showed that food dyes and benzoate preservatives are frequent triggers of hyperactive behavior; in that study, however, common foods such as dairy products, chocolate, grapes, wheat, oranges, and eggs also played a significant role.

Considering that more than 1 in 20 children in some areas of the country is on Ritalin or other drugs for hyperactivity, closer attention should be given to the dietary factors that are causing problems for these children.

Bateman B, et al. The effects of a double blind, placebo controlled, artificial food colourings and benzoate preservative challenge on hyperactivity in a general population sample of preschool children. Arch Dis Child 2004;89:506-511.

Two hundred fifty-one patients with papulopustular rosacea with persistent erythema and telangiectasia were randomly assigned to receive, in double-blind fashion, a 15% azelaic acid gel or 0.75% metronidazole gel. The respective treatments were applied topically twice a day for 15 weeks. Azelaic acid gel was more effective than metronidazole gel, as demonstrated by a greater reduction in the mean number of lesions (-12.9 vs. -10.7; p = 0.003) and by a greater mean percent decrease in inflammatory lesions (-72.7% vs. -55.8%; p < 0.001). An improvement in the severity of erythema was seen in 56% of patients receiving azelaic acid and in 42% of those receiving metronidazole (p = 0.02). Neither treatment had an effect on telangiectasia. Both the investigator's global assessment (p = 0.02) and overall assessment of improvement (p = 0.005) showed a significant advantage for azelaic acid gel. No serious adverse events were reported, although minor skin irritation occurred in 89% and 96% of the patients in the azelaic acid and metronidazole groups, respectively.

Comment: Azelaic acid is a nontoxic 9-carbon dicarboxylic acid that has been shown to be effective as a topical treatment for acne vulgaris, rosacea, and some hyperpigmentary disorders. The results of the present study demonstrate that azelaic acid is at least as effective as, and probably more effective than, standard therapy (topical metronidazole) as a treatment for rosacea. Azelaic acid for topical application is available both by prescription and over the counter; the prescription version costs substantially more than the OTC preparations. While it is generally well tolerated, azelaic acid tends to cause minor skin irritation. It has been said that topical application of azelaic acid can, on rare occasions, cause a loss of pigmentation of normal skin, but some researchers have disputed that statement.

Elewski BE, et al. A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial. Arch Dermatol 2003;139:1444-1450.

One hundred-forty healthy pregnant women hospitalized for delivery and their newborn infants were studied. The presence of cotinine in urine and serum was used to classify mothers as smokers (n = 50) or nonsmokers (n = 90). Smoking and nonsmoking mothers had identical urinary iodine levels on day five after delivery, but smoking was associated with reduced iodine content in breast milk (smokers, 26.0 mcg/L; nonsmokers, 53.8 mcg/L; p < 0.001) and in the infants' urine (smokers, 33.3 mcg/L; nonsmokers, 50.4 mcg/L; p = 0.005). In smokers, iodine transfer into breast milk correlated negatively with urinary cotinine concentration. Smoking mothers had significantly higher serum levels of thiocyanate, which may competitively inhibit iodide transport into breast milk.

Comment: Iodine deficiency during the fetal stage or the first years of life may lead to hypothyroidism, resulting in impaired brain development. During the period of breastfeeding, thyroid function of the infant depends on the presence of adequate amounts of iodine in maternal milk. In addition to any other adverse effects smoking may have on infant development, the results of the present study suggest that smoking while breastfeeding increases the risk of iodine deficiency-induced brain damage in the child. Women who breastfeed should not smoke, but if they do, an iodine supplement should be considered.

Laurberg P, et al. Iodine nutrition in breast-fed infants is impaired by maternal smoking. J Clin Endocrinol Metab 2004;89:181-187.

One hundred-twenty men and women (mean age, 65 years) with age-associated memory impairment were randomly assigned to receive, in double-blind fashion, either 1) placebo, 2) 300 mg/day of soy-derived phosphatidylserine, or 3) 600 mg/day of soy-derived phosphatidylserine for 12 weeks. Assessments were carried out at baseline, after 6 and 12 weeks of treatment, and 3 weeks after treatment was discontinued. Tests of learning and memory, choice reaction time, and planning and attention functions were administered at each assessment. Delayed recall and recognition of a previously learned word list were the primary outcome measures. No significant differences were found between treatment groups in any of the outcome variables. There were also no significant interactions between treatment and severity of memory complaints.

Comment: Phosphatidylserine derived from bovine brain has been shown in numerous studies to have a positive effect on cognitive function in people with age-related cognitive decline and in those with Alzheimer's disease. However, because of fears that cow-brain preparations could cause infectious diseases such as mad-cow disease, this product is not available in the United States. Soy-derived phosphatidylserine, which is commercially available, does not have the same chemical structure as the cow-derived product; consequently, these preparations may not have the same effects on brain function. The results of the present study suggest that the phosphatidylserine available in the US is not effective for prevention or treatment of cognitive decline.

Potentially beneficial treatments for this problem include Ginkgo biloba extract, vitamin B12, dehydroepiandrosterone, and lemon balm (see J Neurol Neurosurg Psychiatry 2003;74:863-866 for information regarding lemon balm).

Jorissen BL, et al. The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment. Nutr Neurosci 2001;4:121-134.

Thirty-one patients with ovarian cancer undergoing chemotherapy (cisplatin plus cyclophosphamide) received 2 capsules 4 times a day of a nutritional supplement that provided daily 60 mg of beta-carotene, 800 mg of vitamin C, 144 mg of vitamin E, 18 mg of riboflavin, and 190 mg of niacin. For half of the patients (assigned randomly, in double-blind fashion) the supplement also provided 200 mcg/day of selenium from high-selenium yeast. After three months, the mean white blood cell count was significantly higher in the selenium group than in the no-selenium group (p < 0.0001), as a result of a smaller decrease from baseline in the selenium group. After two and three months of supplementation, the frequencies of nausea, hair loss, flatulence, abdominal pain, weakness, malaise, and loss of appetite were each significantly lower in the selenium group than in the no-selenium group. The incidences of vomiting and stomatitis were also significantly lower in the selenium group after three months, but not after two months. Selenium supplementation did not reduce the incidence of diarrhea.

Comment: In this study, supplementation with selenium reduced the chemotherapy-induced decline in white blood cell counts and reduced the incidence of side effects in patients with ovarian cancer undergoing treatment with cisplatin plus cyclophosphamide. Other studies suggest that selenium also has direct anti-cancer effects.

Oncologists have expressed concern that co-administration of selenium or other antioxidants along with chemotherapy might block the beneficial effect of the chemotherapy. It is true that many chemotherapeutic drugs induce the formation of free radicals; however, the anticancer effects of these drugs do not, in general, seem to depend on the formation of reactive oxygen species. Therefore, in certain situations, administration of antioxidants might reduce drug side effects without inhibiting the tumor-fighting actions of the drugs. As there are many different chemotherapeutic drugs and many different antioxidants, each of which has a unique pattern of biological activity, a great deal of research needs to be done to determine which antioxidants are safe and desirable to use in combination with which chemotherapy drugs.

Sieja K, Talerczyk M. Selenium as an element in the treatment of ovarian cancer in women receiving chemotherapy. Gynecol Oncol 2004;93:320-327.

Two hundred ninety-eight healthy postmenopausal women (mean age, 50 years) were randomly assigned to receive, in double-blind fashion, tablets providing 150 mg/day of soy isoflavones or placebo for 5 years. Endometrial biopsies were performed at baseline and after 30 months and 5 years. No cases of endometrial hyperplasia were detected after 30 months. After 5 years, of 154 women who received soy isoflavones, 6 (3.9%) were found to have endometrial hyperplasia (5 simple, 1 complex hyperplasia), compared with none of the women receiving placebo (p < 0.05). No cases of endometrial cancer were detected.

Comment: Because soy isoflavones have weak estrogenic effects, the authors of this study hypothesized that supplementation with soy isoflavones might have a proliferative effect on the endometrium. Although the incidence of endometrial hyperplasia was far less than that induced by treatment with unopposed estrogens, isoflavone supplementation was not entirely innocuous, as nearly one in 25 women developed hyperplasia. The dose of soy isoflavones used in this study was approximately two to three times the amount used in most research. Nevertheless, the possibility exists that long-term use of isoflavones could cause uterine hyperplasia, and women taking soy isoflavones should be monitored appropriately.

Unfer V, et al. Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study. Fertil Steril 2004;82:145-148.

A 54-year-old man presented for his first office visit looking for an alternative to prescription medications to treat his newly diagnosed hypertension. His blood pressure had always been normal in the past, but on a routine annual check-up with his internist two weeks previously he was found to have a blood pressure of 158/96 mm Hg. He had been advised to begin taking a beta-blocker and to have his blood pressure rechecked in two weeks. The man had not yet started the antihypertensive medication at the time of his consultation at my office.

Further questioning revealed that the man's blood pressure had been taken in a somewhat noisy environment, with no time taken to get calm, while casually chatting with the doctor, and with his arm resting on the arm of a chair. When I checked the patient's blood pressure after allowing him a quiet period in a dimly lit room, with no talking allowed during the measurement, and with the arm at heart level, it was 126/78 mm Hg. He was asked to return for a repeat measurement in two weeks, at which time it was again 126/78.

Comment: Inaccurate blood pressure measurements, which are all too common in clinical medicine, can lead to potentially dangerous errors in patient management. Proper technique is crucial for obtaining an accurate measurement. The cuff size should be based on the circumference of the midpoint of the upper arm: for 22 to 26.9 cm, use small adult size; for 27 to 32.9 cm, use adult size; and for 33 to 40.9 cm, use large adult size. The patient should be seated in a straight-back chair with both feet on the floor (when patients are sitting on an examining table, the contraction of muscles required to hold their position can increase blood pressure by 10/5 mm Hg. The arm should be at heart level; if it is allowed to hang lower, then the blood pressure reading will be falsely elevated. In addition, blood pressure can rise substantially if the patient is talking during the measurement. Two or more measurements, separated by two minutes, should be taken. If they differ by more than 5 mm Hg, additional measurements should be taken and averaged.

Worcester S. Blood pressure measurement frequently lacks accuracy. Fam Pract News 2004(September 1):16.