One hundred-ten obese men (body mass index of 30 or greater) aged 35 to 55 years, without diabetes, hypertension, or hyperlipidemia, who had erectile dysfunction (defined as a score of 21 or less on the International Index of Erectile Function [IIEF]) were randomly assigned, in single-blind fashion, to one of two groups. The intervention group received detailed advice about how to lose 10% or more of total body weight by reducing caloric intake and increasing physical activity. The control group was given general information about healthy food choices and exercise. After two years, the mean body mass index decreased to a significantly greater extent (p < 0.001) in the intervention group (from 36.9 to 31.2) than in the control group (from 36.4 to 35.7). The mean level of physical activity increased more in the intervention group than in the control group (p < 0.001). The mean IIEF score improved in the intervention group (from 13.9 to 17; p < 0.001), but remained stable in the control group (from 13.5 to 13.6; p = 0.89). After two years, 30.9% of the men in the intervention group and 5.5% of those in the control group (p = 0.001) had an IIEF score of 22 or higher, a score that indicates a high probability of normal erectile function.

Comment: In this age of magical erection-enhancing pills whose names invoke subliminal images of levitation, aggression, vigor, and genitalia, it is important to remember that sexual function is sometimes a reflection of overall health. In the current study, a program of diet and exercise was associated with normalization of sexual function in nearly one-third of obese men with erectile dysfunction. If such an approach works for erectile dysfunction, it is certainly preferable to taking performance-enhancing drugs.

Esposito K, et al. Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial. JAMA 2004;291:2978-2984.

Forty-eight men aged 65 years or older (mean age, 71 years) with a serum testosterone level below the normal range for young adult men (< 12.1 nmol/L) were randomly assigned to receive, in double-blind fashion, either 1) testosterone enanthate, 200 mg intramuscularly every two weeks or 2) placebo for three years. Thirty-five men completed the study. In intent-to-treat analysis, the mean bone mineral density (BMD) of the lumbar spine increased by 10.2% with testosterone and by 1.3% with placebo (p < 0.05 for the difference in the change between groups). The mean change in BMD of the hip was 2.7% with testosterone and -0.2% with placebo (p < 0.05). The mean prostate-specific antigen (PSA) level increased from 1.4 to 1.7 ng/ml with placebo and from 1.0 to 1.4 ng/ml with testosterone; the difference in the change between groups was not significant. The mean prostate volume increased from 32 to 42 ml with placebo and from 29 to 43 ml with testosterone; the difference in the change between groups was not significant.

Comment: These results indicate that administration of testosterone for three years to older men with low serum testosterone levels increased BMD of the lumbar spine and hip. Compared with placebo, testosterone did not significantly increase PSA levels or prostate size. It has been known for some time that testosterone-replacement therapy can improve BMD in older men; however, there has been concern that long-term treatment with this hormone might increase the risk of benign prostatic hyperplasia or prostate cancer. Within the limitations of this study, those concerns appear to be unfounded. Nevertheless, all men receiving testosterone be closely monitored, for the development of both prostate problems and polycythemia.

Amory JK, et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 2004;89:503-510.

The association between use of vitamin supplements during the first six months of life and risk of developing asthma or food allergies during early childhood was assessed in a prospective cohort study of more than 8,000 children. After adjustment for potential confounding variables (including breastfeeding, smoker in the household, race, income, and prematurity), a history of vitamin use within the first six months of life was associated with a 27% increase in risk of asthma in black infants, and a 63% increase in risk of food allergies in exclusively formula-fed children.

Comment: The findings in this study are surprising, because several components of the average multiple vitamin formula (particularly vitamin C and vitamin B6) have been shown to be effective for preventing or treating asthma or allergies. Animal or in vitro studies also suggest that niacinamide and pantothenic acid might be protective. It is conceivable that early supplementation with vitamins causes deleterious changes in the immature immune system or intestinal tract, leading to an increased risk of asthma or allergies.

A more likely explanation for the associations observed in this study is that many pediatric vitamin preparations contain allergenic excipients. One of the leading brands of infant vitamin drops contains not only artificial flavor and color, but also polysorbate 80, a known cause of hypersensitivity reactions. Once infants graduate from liquid to chewable vitamins, it gets worse: the number of artificial yellows, reds, and blues with which they are bombarded in some of these preparations increases to a level that would make a bag of M&Ms blush. Some vitamin manufacturers, on the other hand, take great care to make their products hypoallergenic. Before we conclude that giving vitamins to babies is a bad idea, the results of the current study should be re-analyzed, considering the incidence of asthma and allergies as a function of the specific brands of vitamins used.

Milner JD, et al. Early infant multivitamin supplementation is associated with increased risk for food allergy and asthma. Pediatrics 2004;114:27-32.

One hundred eighty-six people considered at high risk for deep vein thrombosis (DVT) who were undergoing a seven- to eight-hour plane flight were randomly assigned to receive Flite Tabs (Aidan, Tempe, AZ) or placebo at a dose of two capsules two hours before the flight and again six hours later. Each capsule contained 150 mg of a proprietary blend of Pycnogenol and nattokinase (proportions of each not specified). All participants were advised to engage in mild exercise during the flight and to drink 100 to 150 ml of water every hour. In the placebo group, DVT (determined by ultrasound scanning) developed in five subjects (5.4%), and superficial vein thrombosis developed in two subjects (total events: 7 in 92 subjects; 7.6%); all events were asymptomatic. No thrombotic events occurred in the active-treatment group (p < 0.025 for the difference in event rates between groups). Edema of the lower leg increased by a mean of 12% in the placebo group and decreased by a mean of 15% in the active-treatment group (p < 0.02 for the difference in the change between groups).

Comment: Prolonged air travel is associated with DVT, which can lead to pulmonary embolism. The increased risk of DVT during long flights may be due to in part to prolonged bending and compression of veins on the edges of the seat, leading to stasis and thrombosis. Other contributing factors may be immobility, relative hypoxia, decreased fluid intake, and dry air in airplanes. The risk of developing DVT is increased in people with a history of deep or superficial vein thrombosis, coagulation disorders, severe obesity, limited mobility, cancer within the previous two years, cardiovascular disease, or large varicose veins. Compression stockings have been shown to be effective for preventing DVT during long flights.

Nattokinase is a fibrinolytic enzyme purified from the fermented soy food Natto. When taken orally, nattokinase increases fibrinolytic activity in the blood, an effect that would be expected to reduce the risk of thrombosis. Pycnogenol is an extract of a tree bark that has been shown to inhibit platelet aggregation, increase capillary integrity, and decrease the severity of leg edema in people with venous insufficiency. The results of the present study demonstrate that supplementation with nattokinase and Pycnogenol can reduce the incidence of thrombotic events and prevent leg edema in high-risk individuals undergoing a long airline flight.

Cesarone MR, et al. Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial. Angiology 2003;54:531-539.

Twenty patients (aged 18-45 years) with chronic active inflammatory bowel disease (7 with Crohn's disease, 13 with ulcerative colitis) that had failed to respond to various medications were treated with 200 mg/day of dehydroepiandrosterone (DHEA) for eight weeks. Six patients with Crohn's disease (83%) and six with ulcerative colitis (46%) went into remission (i.e., Crohn's disease activity index < 150; clinical activity index 4 or lower for ulcerative colitis). Two other patients (15%) with ulcerative colitis were considered treatment responders (i.e., a decrease in the clinical activity index of more than 4 points). No patient discontinued treatment because of side effects.

Comment: DHEA, a steroid hormone produced by the adrenal glands, testes and ovaries, has a wide range of effects on immune function. Blood levels of DHEA-sulfate, the predominant circulating form of DHEA, are low in patients with ulcerative colitis and Crohn's disease. In previous studies, administration of DHEA reduced disease activity in patients with systemic lupus erythematosus (SLE). As both SLE and inflammatory bowel disease are autoimmune diseases, DHEA has been used by some practitioners to treat inflammatory bowel disease, with apparently good results. The results of the present study suggest that DHEA is an effective treatment for both ulcerative colitis and Crohn's disease.

The dose used in this study was considerably larger than the amount the human body normally secretes. Although no adverse effects were seen, it is possible that long-term administration of high doses of DHEA would cause problems, such as the development of hormone-dependent cancers. For that reason, the lowest effective dose of DHEA should be used. I have observed that when DHEA is used as part of a comprehensive treatment program that includes allergen avoidance and nutritional supplementation, doses of DHEA closer to the physiological range (such as 15-30 mg/day) are helpful for some patients with inflammatory bowel disease.

Andus T, et al. Patients with refractory Crohn's disease or ulcerative colitis respond to dehydroepiandrosterone: a pilot study. Aliment Pharmacol Ther 2003;17:409-414.

Twenty-five patients with end-stage renal disease who had symptoms of restless legs syndrome (RLS) were randomly assigned to receive, in double-blind fashion, a single intravenous infusion of iron dextran (1,000 mg) or placebo. Prior to treatment, none of the patients had evidence of iron deficiency (serum levels of ferritin and percent iron saturation were normal). Compared with baseline, the median RLS symptom score improved by approximately 43% in the active-treatment group after one and two weeks and by 28% after four weeks. The improvement was significant relative to placebo after one and two weeks, but not after four weeks.

Comment: RLS is a common problem, particularly among elderly people. Because the condition responds to dopaminergic drugs, it has been suggested that reduced dopaminergic activity in the brain may play a role in its pathogenesis. Iron is required for the conversion of tyrosine to levodopa, so a deficiency of iron in the brain may lead to reduced dopaminergic activity. Iron supplementation is known to relieve symptoms of RLS in patients with documented iron deficiency. The present study suggests that iron therapy may also be beneficial for some patients whose standard laboratory tests for iron status are normal. Recent studies suggest that patients with RLS have impaired uptake of iron into some portions of the brain. Consequently, a deficiency or iron could exist in the brain, despite normal iron levels in the periphery.

Other interventions that may be beneficial for RLS include cessation of cigarette smoking and supplementation with vitamin E, folic acid, and magnesium. When these treatments do not work, a trial of iron therapy may be considered for non-iron-deficient patients, as long as they have been screened to rule out hemochromatosis.

Sloand JA, et al. A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome. Am J Kidney Dis 2004;43:663-670.

Nineteen hypothyroid women were observed before and throughout their pregnancies. Thyroid-stimulating hormone (TSH) levels were measured every two weeks during the first trimester and monthly thereafter. The dose of levothyroxine was increased to maintain the TSH concentration at preconception values throughout pregnancy. An increase in the levothyroxine dose was necessary during 17 of 20 pregnancies; one woman with a history of thyroid cancer required a decrease in the dose at 26 weeks' gestation. The mean levothyroxine requirement increased by 47% during the first half of pregnancy. The median time at which a dose increase was required was eight weeks' gestation (although increased requirements were seen as early as the fifth week), and the dosage requirement reached a plateau by week 16. This increased dose requirement persisted until delivery.

Comment: Hypothyroidism during pregnancy has been associated with increased fetal mortality and impaired cognitive development of the infant. Previous studies have shown that maternal thyroid hormone requirements increase during pregnancy; however, the timing and amount of levothyroxine adjustment required has not been previously investigated. Based on the results of the present study, the authors suggest that women with hypothyroidism increase their levothyroxine dose by approximately 30% as soon as pregnancy is confirmed. Thereafter, TSH levels should be monitored and the levothyroxine dose adjusted accordingly.

However, in women with normal laboratory tests for thyroid function who are being treated empirically with thyroid hormone (see Gaby AR. Altern Med Rev 2004;9:157-179), the situation is more complicated. Many of these women presumably have subtle tissue resistance to thyroid hormone, either genetic or acquired. If a woman's fetus does not have tissue resistance to thyroid hormone, then increasing the dose of thyroid hormone during pregnancy would expose the fetus to a hyperthyroid environment, which can have deleterious effects on the fetus, including miscarriage. On the other hand, some women had been infertile until they began empirical therapy with thyroid hormone; in those women, failure to increase the dose during pregnancy could potentially result in a miscarriage. In my female patients with normal laboratory tests for thyroid function whose infertility problems appeared to be corrected with thyroid hormone, I have usually not changed the dose during pregnancy, and maternal and fetal outcomes have so far been acceptable. Of course, each case should be considered on an individual basis.

Alexander EK, et al. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. N Engl J Med 2004;351:241-249.

One hundred seventy-three patients with somatization disorder, undifferentiated somatoform disorder, or somatoform autonomic dysfunction, but not major depression, were randomly assigned to receive, in double-blind fashion, 300 mg of St. John's wort extract LI 160 twice a day or placebo for six weeks. Six outcome measures were evaluated as a combined measure by means of the Wei Lachin test: Somatoform Disorders Screening Instrument - 7 days, somatic subscore of the Hamilton Anxiety Scale, somatic subscore of the Symptom Check List 90 Revised, subscores "improvement" and "efficacy" of the Clinical Global Impression, and the global judgment of efficacy by the patient. In intent-to-treat analysis, for each of the six primary efficacy measures as well as for the combined test, St. John's wort was significantly more effective than placebo (p < 0.0001). Some 45.4% of the patients receiving St. John's wort were classified as responders, compared with 20.9% of those receiving placebo (p = 0.0006). Overall tolerability of St. John's wort was equivalent to that of placebo.

Comment: Somatoform disorders are characterized by chronic multiple physical symptoms that cannot be explained by any underlying disease condition. Patients with somatoform disorders remain convinced they are physically ill despite numerous negative medical evaluations. Patients with somatoform disorders spend an average of seven days per month in bed. The results of the present study demonstrate that administration of 300 mg of St. John's wort extract LI 160 twice a day is safe and effective in the treatment of somatoform disorders.

Muller T, et al. Treatment of somatoform disorders with St. John's wort: a randomized, double-blind and placebo-controlled trial. Psychosom Med 2004;66:538-547.