Lactobacillus GG for prevention of childhood eczema
One hundred fifty-nine pregnant women who had at least one first-degree relative (or partner) with atopic eczema, allergic rhinitis, or asthma were randomly assigned to receive, in double-blind fashion, Lactobacillus GG (1010 colony-forming units per day) or placebo for 2-4 weeks before expected delivery. After delivery, breastfeeding mothers continued their respective treatment, whereas non-breastfeeding infants were given the active treatment or placebo orally for 6 months. At 2 years of age, the prevalence of atopic eczema in the Lactobacillus GG group was 23.5%, compared with 45.6% in the placebo group (48.4% reduction; p = 0.008).

Comment: These results suggest that supplementation with the probiotic agent Lactobacillus GG can prevent the development of atopic eczema in high-risk children. Lactobacillus GG may work by enhancing immune function, by improving the integrity of the developing gut, or by some other mechanism. Supplementing with this organism does not appear to cause adverse effects either in pregnant women or young children.

Kalliomaki M, et al. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 2001;357:1076-1079.

High-dose folic acid for psoriasis
Seven patients with long-standing psoriasis were given 20 mg of folic acid 4 times per day. Marked improvements were noted after 3-6 months of treatment. Three additional patients who had previously received methotrexate treatment for psoriasis were also given folic acid. In one patient, new lesions appeared all over the trunk in places where they had never existed. One patient showed decided worsening and the third patient improved considerably.

Comment: The rationale for using high-dose folic acid is based on the fact that allopurinol, a xanthine oxidase inhibitor, is effective against psoriasis. The author of the present study has found that folic acid fortified with specific amounts of ascorbic acid (to keep it in the reduced state as tetrahydrofolate) is also an effective xanthine oxidase inhibitor. Although no controlled trials have been done with folic acid, other clinicians have observed the same beneficial effect against psoriasis that Oster reported more than a quarter-century ago. Methotrexate interferes with folic acid metabolism and, for reasons that are not clear, appears to cause an adverse reaction to high-dose folic acid in some cases. However, for patients who have not previously been treated with methotrexate, folic acid appears to be a safe and promising therapy for chronic psoriasis. Of course, when using high-dose folic acid, it is important to remember that it can mask the laboratory diagnosis of pernicious anemia.

Oster KA. A cardiologist considers psoriasis. Cutis 1977;20:39-41.

Eating fish for a better pregnancy outcome
The relationship between seafood consumption and risk of pre-term delivery and low birth weight was assessed in a prospective cohort study of 8,729 Danish pregnant women. The incidence of pre-term delivery was 7.1% among women who never consumed fish, compared with 1.9% among women in the highest category of fish intake (i.e., the highest quintile among women who consumed any fish). The adjusted odds ratio for pre-term delivery was 3.6 in the zero-consumption group, compared with the highest-consumption group. Most of the risk reduction was seen between zero intake and a daily intake of 15 g of fish, corresponding to 150 mg of omega-3 fatty acids. Estimates of risk for low birth weight were similar to those for pre-term delivery.

Comment: These results suggest that consuming as little as 15 g (one-half ounce) of fish per day or 150 mg/day of omega-3 fatty acids (provided by 500 mg/day of fish oil) during pregnancy might reduce the incidence of pre-term delivery and low-birth-weight babies. In addition to this potential benefit, eating fish supplies the growing fetus with substantial amounts of docosahexaenoic acid (DHA), which plays a critical role in development of the brain and retina. Concern has been raised that eating too much fish, particularly tuna, may expose the fetus and nursing infant to excessive amounts of mercury. Therefore, it is important for pregnant and lactating women not to overdo their fish intake.

Some have suggested that alternative sources of omega-3 fatty acids, such as flaxseed oil, would produce the same benefits as fish oil, without the potential risks. Flaxseed oil contains large quantities of alpha-linolenic acid, which is metabolized in the body into eicosapentaenoic acid (EPA), and then to DHA. However, the capacity of infants (particularly premature ones) to convert alpha-linolenic acid to DHA may be limited. Studies have shown that eating flaxseed oil does not increase the concentration of DHA in breast milk, whereas consuming DHA does increase breast-milk levels of DHA. Consuming flaxseed oil does increase breast-milk concentrations of EPA, which might then be converted by the infant into DHA. However, until more is known, consuming at least small amounts of pre-formed DHA seems like a good idea for pregnant and lactating women.

Olsen SF, et al. Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: prospective cohort study. BMJ 2002;324:447-450.

Genistein reverses bone loss
Ninety healthy postmenopausal women (aged 47-57 years) with osteopenia (bone mineral density [BMD] of the femoral neck of less than 0.795 g/cm2), were randomly assigned to receive, in double-blind fashion, either 1) continuous hormone-replacement therapy (HRT; 1 mg of 17beta-estradiol combined with 0.5 mg of norethisterone acetate daily), 2) genistein (54 mg/day), or 3) placebo for 1 year. Genistein significantly reduced the excretion of pyridinium cross-links (an indicator of bone resorption) at 6 and 12 months; a similar decrease was seen in the HRT group. Genistein also significantly increased serum levels of bone-specific alkaline phosphatase and osteocalcin (markers of bone formation) at 6 and 12 months, whereas HRT significantly decreased these values at 6 and 12 months. At 12 months, compared with baseline, the mean BMD of the femoral neck increased by 3.6% in the genistein group and by 2.4% in the HRT group, compared with a 0.65% decrease in the placebo group (p < 0.01 for each active treatment vs. placebo). At the lumbar spine the mean changes in BMD were 3.0% for genistein, 3.8% for HRT, and -1.6% for placebo (p < 0.001).

Comment: These results indicate that administration of genistein (an isoflavone present in soybeans) to osteopenic postmenopausal women reduced bone resorption, increased bone formation, and increased BMD of the femoral neck and lumbar spine. The effect on BMD was similar to that of conventional hormone-replacement therapy. The results of this study are consistent with those of previous research, in which genistein stimulated osteoblastic bone formation, inhibited osteoclastic bone resorption, and prevented bone loss in ovariectomized rats. Beneficial effects of isoflavone-rich soy protein on BMD have also been reported in both animals and postmenopausal women. The effect of genistein may be mediated, in part, by its estrogenic activity. However, the response to genistein in the present study differed from that of conventional HRT. Specifically, both treatments reduced markers of bone resorption, but only genistein increased markers of bone formation. Because their actions are not the same, it is possible that genistein (or soy protein) might enhance the effect of HRT; it is also possible that soy isoflavones might increase the risks associated with HRT. Additional research is needed to investigate these possibilities.

Morabito N, et al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. J Bone Miner Res 2002;17:1904-1912.

Nutritional supplement effective against bipolar disorder
Fourteen patients (aged 19-46 years) with a DSM-IV diagnosis of bipolar disorder, who were taking a mean of 2.7 psychotropic medications each, were treated for 6 months with a broad-based nutritional supplement (E.M. Power+), containing the following (daily doses): vitamin A (3,333 IU), vitamin C (250 mg), vitamin D (400 IU), vitamin E (100 IU), thiamine (5 mg), riboflavin (5.5 mg), niacinamide (25 mg), pyridoxine (7 mg), folic acid (400 mcg), vitamin B12 (250 mcg), biotin (25 mcg), pantothenic acid (6 mg), calcium (550 mg), magnesium (250 mg), iron (6 mg), phosphorus (350 mg), iodine (75 mcg), zinc (20 mg), selenium (100 mcg), copper (3 mg), manganese (4 mg), chromium (250 mcg), molybdenum (66 mcg), potassium (100 mg), and a proprietary blend (doses not specified) of DL-phenylalanine, L-glutamine, citrus bioflavonoids, grape seeds, choline, inositol, Ginkgo biloba, L-methionine, germanium, boron, vanadium, and nickel.

At baseline and periodically thereafter, patients were assessed with the Hamilton Rating Scale for Depression (HAM-D), the Brief Psychiatric Rating Scale (BPRS), and the Young Mania Rating Scale (YMRS). For the 11 patients who completed the trial, the mean HAM-D decreased (improved) from 19.0 at baseline to 5.4 at the last visit (71% improvement; p < 01); the mean BPRS score decreased (improved) by 79%; p < 0.05); the mean YMRS score decreased (improved) by 60% (p < 0.01); and the need for psychotropic medications decreased by 63% (p < 0.01). In two cases, the supplement replaced psychotropic medication and the patients remained well. The only reported side effect was nausea, which was infrequent, minor, and transient. In general, improvement began within two weeks of starting the nutritional supplement.

Comment: This open-label study suggests that a broad-spectrum nutritional supplement can reduce the severity of illness in some patients with bipolar disorder. Although there was no control group in this study, the magnitude of the improvement was greater than one might expect from a placebo effect alone. Other investigators have also found this supplement to be effective for bipolar disorder (J Clin Psychiatry 2001;62:933-935). This product should be used cautiously, as it may potentiate the effect of antipsychotic drugs, possibly increasing their toxicity. Additional research is needed to determine the optimal way to transition patients from psychotropic drugs to nutritional therapy. E.M. Power+ was originally manufactured by Evince International; it is currently manufactured by Synergy Group of Canada (1-888-878-3467). The monthly retail cost is $68.00.

Kaplan BJ, et al. Effective mood stabilization with a chelated mineral supplement: an open-label trial in bipolar disorder. J Clin Psychiatry 2001;62:936-944.

Breast-feeding reduces risk of obesity
A population-based sample of 32,200 Scottish children was studied at age 39-42 months. The prevalence of obesity (defined as body mass index [BMI] at or above the 95th percentile) was 9.1% in those who had been formula-fed and 7.2% in those who had been breast-fed. The prevalence of obesity was 20.8% lower in children who had been breast-fed than in those who had been formula-fed. After adjustment for birthweight, gender, and socioeconomic status, the risk of obesity was significantly lower by 28% in breast-fed children than in formula-fed children.

Comment: These results suggest that breast-feeding reduces the risk of becoming obese later in childhood. Although the mechanism by which breast-feeding might prevent obesity is not known, there are several possible explanations. First, the higher content of docosahexaenoic acid (DHA) in human milk than in infant formulas may promote better development of the brain, including the area in the hypothalamus that controls appetite. Second, as many formulas contain refined sugars, feeding such formulas might promote the development of reactive hypoglycemia, resulting in cravings for refined carbohydrates. Third, infants who experience the comfort of the breast might be less likely to seek substitute forms of comfort, such as overeating. Whatever the mechanism, this study provides one more reason for mothers to breast-feed their babies.

Armstrong J, et al. Breastfeeding and lowering the risk of childhood obesity. Lancet 2002;359:2003-2004.

Vegetarian source of vitamin B12
Feeding nori (dried purple laver, a commonly consumed seaweed) to vitamin B12-deficient rats significantly improved vitamin B12 status, as demonstrated by the elimination of methylmalonic acid from the urine and by a significant increase in hepatic vitamin B12 concentrations (especially adenosylcobalamin). The amount of total vitamin B12 in nori, determined by 1) Lactobacillus bioassay and 2) chemiluminescent assay with hog intrinsic factor, was estimated to be 55 and 59 mcg/100 g dry weight, respectively. Five different biologically active vitamin B12 compounds were identified in nori (cyanocobalamin, hydroxocobalamin, sulfitocobalamin, adenosylcobalamin and methylcobalamin).

Comment: Vegetarians are at risk of developing vitamin B12 deficiency, as this vitamin is present almost exclusively in animal products. Several different seaweeds have been claimed to contain vitamin B12. The research in this area is conflicting, however, and many of the studies purporting to show vitamin B12 activity did not distinguish between true vitamin B12 and biologically inactive vitamin B12 analogues. The present study provides strong evidence that nori does, indeed, contain bioavailable forms of vitamin B12.

Takenaka S, et al. Feeding dried purple laver (nori) to vitamin B12-deficient rats significantly improves vitamin B12 status. Br J Nutr 2001;852:699-703.

Hawthorn (crataegus) effective against heart failure: double-blind study
Two-hundred nine patients (mean age, 68 years) with chronic congestive heart failure (New York Heart Association [NYHA] class III) were randomly assigned to receive, in double-blind fashion, crataegus extract WS 1442 standardized to contain 18.75% oligomeric procyanidins (900 or 1,800 mg/day) or placebo for 16 weeks. After 16 weeks of treatment, the maximal tolerated workload during a bicycle exercise test had increased to a significantly greater extent in the high-dose crataegus group than in the low-dose crataegus group (p = 0.01) and the placebo group (p < 0.02). Symptoms of heart failure decreased to a significantly greater degree in the high-dose (p = 0.004) and low-dose (p = 0.04) crataegus groups than in the placebo group; the high dose was slightly but not significantly more effective than the low dose. No serious adverse events were reported, and the number of adverse events was nearly twice as high in the placebo group as in the crataegus group.

Comment: This study demonstrated that crataegus extract WS 1442 increased exercise capacity and reduced signs and symptoms of heart failure, without causing significant adverse effects, in patients with NYHA class III congestive heart failure. Hawthorn has been used for many decades by a minority of doctors to treat heart failure. Recently, several controlled clinical trials have been published that have confirmed its safety and effectiveness. Despite this evidence, conventional cardiologists have shown little interest in using this herbal treatment. Now that the American Heart Journal, a conventional cardiology journal, has published a positive study on hawthorn, perhaps more doctors will prescribe this herb for patients with heart failure.

Tauchert M. Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure. Am Heart J 2002;143:910-915.

Literature Review & Commentary
by Alan R. Gaby, MD
301 Dorwood Drive • Carlisle, Pennsylvania 17013

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