Serum from 12 women who were or had been pregnant with a fetus with a neural tube defect (cases) and from 20 control women with current or prior normal pregnancies was analyzed for antibodies against human placental folate receptors. Serum from 75% of cases, compared with only 10% of controls, contained antibodies against folate receptors (p < 0.001). These antibodies blocked the binding of folic acid to folate receptors on placental membranes and blocked the uptake of folic acid by a human carcinoma cell line.

Comment: Periconceptional administration of folic acid reduces the incidence of neural tube defects (NTDs) in the offspring. This benefit occurs among pregnant women who have no clinical evidence of folic acid deficiency, suggesting that some women have a higher-than-normal requirement for folic acid that cannot be met by a typical diet. Part of this increased requirement may be explained by genetic variations in the 5,10-methylenetetrahydrofolate reductase allele; however as less than 20% of humans have the variant allele, that factor alone cannot explain the 70-80% reduction in NTDs that results from folic acid supplementation. The current study indicates that a high proportion of women who give birth to a child with a NTD have anti-folate antibodies which may block the uptake of folic acid by the placenta, thereby depriving the fetus of adequate amounts of the vitamin. Presumably, this impaired uptake can be overcome by increasing the amount of folic acid ingested.

The importance of folic acid supplementation prior to and during pregnancy has been amplified by recent evidence that folic acid taken during the first 6 weeks of gestation may reduce the incidence of congenital heart defects (ventricular septal defects and conotruncal defects) by more then 50% (Fam Pract News, December 15, 2003, p. 10.).

Rothenberg SP, et al. Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect. N Engl J Med 2004;350:134-142.

Fine-needle aspiration cytology of the thyroid gland was performed on 219 patients complaining of fatigue of more than one year’s duration. Eighty-seven patients (40%) were found to have definite histological evidence of chronic lymphocytic (autoimmune) thyroiditis. TSH levels were widely scattered, with a median of 3.8 mU/L and a range of less than 0.9 to greater than 15 mU/L (normal range, 0.1 to 5.0 mU/L). The clinical response to thyroxine therapy was equally favorable among patients with lymphocytic thyroiditis, irrespective of their initial TSH level. In a follow-up letter (Lancet 2003;361:1305), the writers point out that thyroid autoantibodies (peroxidase, thyroglobulin, or both) were present in only half of the patients with definite lymphocytic thyroiditis.

Comment: Although hypothyroidism is a well-recognized cause of fatigue, there is a great deal of controversy about how best to diagnose this condition. Most doctors will rule out a diagnosis of hypothyroidism if the TSH level is normal. The results of this study, however, suggest that chronic autoimmune thyroiditis is associated with clinical hypothyroidism, even in the presence of normal TSH values. Furthermore, fine-needle aspiration cytology of the thyroid gland is a more sensitive method of identifying thyroid autoimmunity than are measurements of thyroid autoantibodies. The results of this study suggest that approximately 40% of patients with chronic fatigue will benefit from thyroid-replacement therapy, and that standard thyroid-function tests are not sensitive enough to identify who will respond to such therapy. In lieu of an invasive biopsy of the thyroid gland, a careful therapeutic trial of thyroid hormone seems warranted for patients with chronic fatigue who have clinical evidence of hypothyroidism.

Wikland B, et al. Fine-needle aspiration cytology of the thyroid in chronic fatigue. Lancet 2001;357:956-957.

Twenty-four patients (mean age, 56 years) with moderate-to-severe rheumatoid arthritis consumed a very-low-fat (10% of energy) vegan diet for 4 weeks. Compared with baseline, the severity of pain decreased by 30.6% (p < 0.004), the tender-joint score decreased by 29.1% (p < 0.01), the joint-swelling score decreased by 70.3% (p < 0.02), and the severity of morning stiffness improved by 26.5% (p < 0.04).

Comment: These results suggest that consumption of a very-low-fat vegan diet can produce significant symptom relief in patients with moderate-to-severe rheumatoid arthritis. There are several possible explanations for the positive response, other than a placebo effect. First, a vegan diet eliminates common allergens (such as cow’s milk) that might be a triggering factor for joint inflammation. Second, by eliminating meat, a major dietary source of the pro-inflammatory fatty acid arachidonic acid, a vegan diet may reduce the overall degree of inflammation in the body. Third, plant foods contain a wide array of phytochemicals, some of which have anti-inflammatory activity. Vegan diets are deficient in vitamin B12 and also may contain inadequate amounts of zinc, iron, vitamin D, and protein. Individuals consuming a vegan diet should make sure their diet is balanced, and should take appropriate supplements.

McDougall J, et al. Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis. J Altern Complement Med 2002;8:71-75

One hundred-twenty women with active systemic lupus erythematosus (SLE) were randomly assigned to receive, in double-blind fashion, 200 mg/day of DHEA or placebo for 24 weeks. During the study, 18.3% of the patients in the DHEA group experienced a flare-up of their disease, compared with 33.9% of those in the placebo group. The incidence of disease flare-ups was 46% lower in the DHEA group than in the placebo group (p < 0.05). The mean change in the patients’ global assessment was significantly better in the DHEA group than in the placebo group (14.9% improvement vs. 16.1% worsening; p = 0.005). The mean improvement in the Systemic Lupus Activity Measure score was 25.3% in the DHEA group and 19.3% in the placebo group (difference not significant). No serious side effects were seen, but DHEA treatment increased testosterone levels and increased the incidence of acne.

Comment: These results confirm those of earlier studies indicating that high-dose DHEA is beneficial in the treatment of women with SLE. Although DHEA caused acne in this study, it was otherwise well tolerated, and should be considered as part of the overall treatment of this potentially serious disease.

The markedly higher prevalence of SLE among women, as compared with men, suggests that high concentrations of androgens may somehow protect against the development of this disease. DHEA is a weak androgen that has been shown to reduce disease severity in animal models of lupus. Plasma levels of DHEA-sulfate have been found to be lower in patients with untreated SLE than in healthy controls. Furthermore, treatment with glucocorticoids such as prednisone will further deplete DHEA by shutting down its main source of production, the adrenal glands. Whether physiological doses of DHEA (such as 5-15 mg/day for women or 10-30 mg/day for men), as part of a comprehensive program of dietary modification and nutritional supplementation, would be beneficial has not been investigated, although some clinicians have the impression that it is helpful in some cases.

Chang DM, et al. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus. A multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002;46:2924-2927.

Twenty-nine healthy premenopausal women were randomly assigned to receive, immediately following menses, a vaginal gelatin capsule containing either 1) 109 Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 or 2) 109 Lactobacillus rhamnosus GG. Women in group 1 had significantly higher intravaginal levels of one or both organisms at day 14 than did those in group 2 (p < 0.01). Both GR-1 and RC-14 inhibited the growth of Candida albicans. In a previous study, 50 women who received GR-1 and RC-14 by weekly vaginal application for up to one year experienced no cases of yeast vaginitis, compared with an expected 200 episodes in this number of women.

Comment: These findings suggest that administration of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 promotes healthy vaginal ecology and may prevent the development of yeast vaginitis. In contrast, Lactobacillus GG, which has been well documented as a beneficial organism for the human digestive tract, was less able to colonize the genitourinary tract. The results of this study suggest that the appropriate choice of probiotic may depend on the area of the body being treated. Note: Dr. Reid holds a patent on Lactobacillus rhamnosus GR-1 and L. fermentum RC-14. These lactobacillus strains are not yet commercially available.

Cadieux P, et al. Lactobacillus strains and vaginal ecology. JAMA 2002;287:1940-1941.

Forty-four patients with idiopathic, intractable pruritus ani were randomly assigned to receive, in double-blind fashion, topical capsaicin (0.006%) or placebo (menthol 1%) ointment for four weeks. After a one-week washout period, each patient received the alternate treatment for an additional four weeks. The ointment was prepared by diluting Zostrix® (0.025%) in white soft paraffin. The treatment was applied in a very thin layer to the perianal area, three times a day. Prior to the study, a pilot study was performed on five patients, to determine which of two concentrations of capsaicin (0.012% or 0.006%) had the best profile of effectiveness and side effects. At the end of the controlled study, responders from both groups continued capsaicin in open-label fashion. Thirty-one (70%) of 44 patients experienced relief during capsaicin treatment and did not respond to menthol; all patients not responding to capsaicin also failed to respond to menthol (p < 0.0001). The mean pruritus score improved by approximately 60% in the group as a whole during capsaicin treatment. The beneficial effect was immediate in 24 patients and occurred within 3 days in 7 patients. Four patients discontinued treatment because of side effects (perianal burning in 3, urticaria in 1). All patients had some perianal burning following each capsaicin application; this decreased significantly after four weeks of application, but did not disappear completely. During a mean follow-up period 10.9 months, 29 responders needed to apply capsaicin a mean of every 1.6 days (range 0.5-7 days) to remain symptom-free or nearly symptom-free.

Comment: Pruritus ani is a common problem characterized by an intense urge to scratch around the anal area. Causes include persistent moisture around the anus from excessive sweating, sensitivity to various foods and beverages, fungal infection, and skin diseases such as eczema or psoriasis. In many cases, the cause of the problem cannot be identified, and attempts to treat it are unsuccessful. The results of the present study indicate that capsaicin, a substance found in cayenne pepper, is a safe and highly effective treatment for severe intractable idiopathic pruritus ani. While the mechanism by which capsaicin relieves pruritus ani is not entirely clear, it may work by depleting from the skin a chemical messenger known as substance P that plays a role in the perception of itching.

Lysy J, et al. Topical capsaicin - a novel and effective treatment for idiopathic intractable pruritus ani: a randomised, placebo controlled, crossover study. Gut 2003;52:1323-1326.

Of 31 consecutive Brazilian patients (mean age, 67.5 years) with Parkinson's disease, all were found to have evidence of riboflavin deficiency, as assessed by plasma FAD concentrations and the erythrocyte glutathione-reductase activation coefficient. In contrast, only 3 of 10 patients with dementia had evidence of riboflavin deficiency. Nineteen of the patients with Parkinson’s disease were treated with 30 mg of riboflavin 3 times a day for 6 months and at the same time eliminated all red meat from their diet. After three months, all patients showed improved motor capacity; during the following three months, five patients continued to improve, while the others maintained their previous level of improvement. The average motor capacity increased from 44% to 71% after six months (p < 0.001).

Comment: This study demonstrates that riboflavin deficiency is common in Brazilian patients with Parkinson’s disease and suggests that riboflavin supplementation may improve their clinical condition. The mechanism of action of riboflavin may involve preventing glutathione depletion or improving mitochondrial energy metabolism. Whether or not the elimination of red meat from the diet played a role in the improvement is not known. The digestion of red meat releases hemin, a potential neurotoxin.

Coimbra CG, Junqueira VBC. High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson's disease patients. Braz J Med Biol Res 2003;36:1409-1417.

Twenty-eight patients (aged 18-60 years) with major depression were randomly assigned to receive, in double-blind fashion, menhaden oil (providing 4.4 g/day of eicosapentaenoic acid and 2.2 g/day of docosahexaenoic acid) or placebo for eight weeks. All patients except one in each group had been receiving antidepressant medication for at least four weeks and continued on those medications during the trial. The improvement in symptoms, as determined by a lower score on the 21-item Hamilton Rating Scale for Depression (HAM-D), was significantly greater in the active-treatment group than in the placebo group after four (p < 0.005), six (p = 0.001) and eight (p = 0.001) weeks. After 8 weeks, the mean reduction in the HAM-D score was approximately 14 points in the active-treatment group, compared with approximately 6 points in the placebo group (p = 0.001).

Comment: In this study, supplementation with omega-3 fatty acids from fish (menhaden) oil, as an adjuvant to antidepressant medication, was beneficial in the treatment of major depression. Previous studies using either fish oil or purified EPA (administered as the ethyl-ester of EPA) have found similar results, although purified docosahexaenoic acid given by itself was ineffective. Thus, the beneficial effects seen with fish oil appear to be due to the EPA component. Depression is associated with low concentrations of omega-3 fatty acids in plasma and red blood cells. EPA is believed to modulate mood through an effect on cell membranes and on signal transduction systems.

Su KP, et al. Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol 2003;13:267-271.