Sixteen women with postpartum depression were randomly assigned to receive 0.5 g/day, 1.4 g/day, or 2.8 g/day of omega-3 fatty acids from fish oil for eight weeks. In the group as a whole, the mean score on the Hamilton Rating Scale for Depression decreased (improved) by 48.8% (from 19.1 to 10.0). None of the different fish oil doses was significantly more effective than the other doses. The lowest dose used in this study was equivalent to 4.7 g/day of fish oil.

Comment: Previous studies have suggested that consuming adequate amounts of long-chain omega-3 fatty acids (i.e., eicosapentaenoic acid and docosahexaenoic acid from fish oil) during pregnancy may reduce the incidence of preterm delivery and enhance the development of the brain and visual system of the fetus. The results of the present study suggest that fish oil may also be useful for treating (and presumably preventing) postpartum depression. It is important for pregnant and nursing women to use fish oil products that are low in mercury, so as not to expose the fetus and infant to excessive amounts of this toxic metal. Supplementing with alpha-linolenic acid from flaxseed oil or other vegetable oils may not be as effective as using fish oil, because the capacity of the body to convert alpha-linolenic acid to eicosapentaenoic acid and docosahexaenoic acid is limited.

Other treatments that have been successful in my experience for treating postpartum depression include 1) intramuscular injections of vitamin B12 (1,000 mcg) and folic acid (2.5 mg) once or twice a week for several weeks and 2) low doses of thyroid hormone when the clinical or laboratory picture is suggestive of hypothyroidism.

Freeman MP, et al. Randomized dose-ranging pilot trial of omega-3 fatty acids for postpartum depression. Acta Psychiatr Scand. 2006;113:31-35.

Eleven female asylum seekers from Bosnia, Afghanistan, Somalia, or Albania who were living in Switzerland presented with musculoskeletal pain associated with subnormal serum concentrations of 25-hydroxyvitamin D. Symptoms included bone pain, proximal muscle weakness, change in gait, or fatigue. In all cases, exposure to sunlight was minimal. Treatment in most cases was 300,000 IU of vitamin D3 once a month intramuscularly plus 1,000 mg/day of calcium and 800 IU/day of vitamin D3 orally. In most cases, symptoms disappeared within one to three months, although one patient needed seven months of treatment.

Comment: Numerous studies over the past 10 years have shown that vitamin D deficiency is more prevalent than most doctors realize. Symptoms of vitamin D deficiency include musculoskeletal pain and weakness that may be confused with fibromyalgia or chronic fatigue syndrome. The main contributing factor to vitamin D deficiency is inadequate sunlight exposure. Some people purposely avoid the sun because of fear of skin cancer and photoaging. Others fail to obtain adequate amounts of sunlight exposure because they spend most of their time indoors or because they live in areas where insufficient amounts of sunlight reach the earth's surface (e.g., northern latitudes or cities with tall buildings). Some women cover themselves for religious reasons.

Most people do not require a large amount of sun exposure to achieve adequate vitamin D status. According to Dr. Michael Holick, a vitamin D expert, exposure of the arms and legs or the hands, arms, and face to sunlight for five to 15 minutes two to three times a week between 10 a.m. and 3 p.m. during the spring, summer, and autumn is usually enough for adequate vitamin D production. People who are obese, elderly, or black have a reduced capacity to synthesize vitamin D in the skin.

Vitamin D deficiency should be considered in patients with fatigue or musculoskeletal symptoms who do not obtain adequate sunlight exposure.

de Torrente de la Jara G, Pecoud A, Favrat B. Musculoskeletal pain in female asylum seekers and hypovitaminosis D3. BMJ. 2004;329:156-157.

Fifteen patients with bipolar disorder consumed a diet that contained less than 10% of the usual amount of inositol. Six of the patients were rapid cyclers who had responded inadequately to lithium or valproate in different phases of illness; two were lithium-treated outpatients with residual symptoms, and seven were lithium-treated inpatients with acute mania who had not responded to treatment. A marked reduction in the severity of the disease was seen in 10 of the 15 patients within the first 7-14 days of treatment, including five of six rapid cyclers, four of seven non-responding acute manic patients, and one of two outpatients with residual symptoms.

Comment: One theory to explain the beneficial effect of lithium in the treatment of mania is that the drug depletes inositol by inhibiting inositol monophosphatase. If that theory is correct, than consumption of a low-inositol diet might also be beneficial. Wheat contains large amounts of inositol, so a low-inositol diet would presumably be wheat-free, and also free of other common allergens such as legumes and nuts. It is possible that some of the improvement observed in this study was due to the avoidance of allergenic foods, rather than to inositol depletion. I have worked with several bipolar patients in whom consumption of allergenic foods was a clear trigger for their psychiatric symptoms.

In a previous study, supplementation with 6 g/day of inositol improved lithium-induced psoriasis without apparently interfering with the beneficial effects of lithium. In another study of 14 patients with various lithium-related side effects, administration of 3 g/day of inositol relieved the side effects in the majority of cases, while appearing to aggravate psychiatric symptoms in only one of the 14 patients. Thus, it is not clear to what extent inositol exacerbates the symptoms of bipolar disorder. Whether the improvement observed in the present study is due to inositol depletion or to the avoidance of allergenic foods, the results suggest that some patients with bipolar disorder respond to dietary modifications.

Shaldubina A, et al. Inositol deficiency diet and lithium effects. Bipolar Disord. 2006;8:152-159.

Salt has been iodized in China since 1996, resulting in an increase in iodine intake throughout the country. In a 1999 study, researchers observed an increase in the prevalence of autoimmune thyroiditis, overt hypothyroidism, and subclinical hypothyroidism with increasing iodine intake in cohorts from three regions of China with different levels of iodine intake: "mildly deficient" (median urinary iodine excretion, 84 mcg/L), "more than adequate" (median, 243 mcg/L), and "excessive" (median, 651 mcg/L). Of the 3,761 subjects enrolled in the original study, 3,018 (80.2%) participated in a five-year follow-up study. During the follow-up period, among subjects with mildly deficient iodine intake, more than adequate intake, and excessive intake, the cumulative incidence of autoimmune thyroiditis was 0.2%, 1.0%, and 1.3%, respectively; that of subclinical hypothyroidism, 0.2%, 2.6%, and 2.9%, respectively; and that of overt hypothyroidism, 0.2%, 0.5%, and 0.3%, respectively. The differences in incidence for mildly deficient vs. more than adequate or excessive intake were statistically significant for autoimmune thyroiditis (p = 0.01 to 0.03) and for subclinical hypothyroidism (p < 0.001). The authors concluded that more than adequate or excessive iodine intake may lead to autoimmune thyroiditis and hypothyroidism.

Comment: Iodine deficiency remains an important problem in some parts of the world, and iodine intake should be increased in people whose intake is inadequate. High-dose iodine therapy also has a role in clinical medicine, particularly in the treatment of fibrocystic breast disease. However, people taking large amounts of iodine should be monitored for the development of thyroid abnormalities.

Teng W, et al. Effect of iodine intake on thyroid diseases in China. N Engl J Med. 2006;354:2783-2793.

One hundred-fifty overweight or obese infertile women (mean age, 29 years; range, 18-39 years) with polycystic ovary syndrome (PCOS) who had failed to ovulate after treatment with clomiphene citrate were randomly assigned to receive, in double-blind fashion, 600 mg of N-acetylcysteine (NAC) twice a day or placebo along with clomiphene citrate (100 mg/day) for five days starting at day three of the cycle. Compared with placebo, NAC significantly increased both the ovulation rate (49.3% vs. 1.3%; p < 0.0001) and the pregnancy rate (21.3% vs. 0%; p = 0.00006). No cases of ovarian hyperstimulation syndrome were reported in the NAC group. Two miscarriages occurred.

Comment: Clomiphene citrate is frequently used to induce ovulation in women with PCOS. Approximately 70% of women treated with this drug experience a return of menstruation and ovulation and 30% become pregnant within three months of treatment. The results of the present study suggest that the combination of NAC and clomiphene citrate is beneficial for some women with PCOS who have failed to respond to clomiphene citrate alone. While the mechanism of action of NAC is not known, it may work by improving the insulin resistance that is frequently associated with PCOS.

Rizk AY, et al. N-acetyl-cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with polycystic ovary syndrome. Fertil Steril. 2005;83:367-370.

Thirty-six women (mean age, 33.3 years; range, 20-45 years) with a history of idiopathic menorrhagia (excessive menstrual bleeding) for a mean duration of 11.7 months received 1,000 mg/day of Daflon (containing 90% diosmin and 10% hesperidin) beginning five days prior to the expected onset of menstruation and continuing until the end of bleeding for three cycles. In 70% of the patients, the total amount of bleeding decreased by 50% and the duration of bleeding decreased by one-third. There was a 50% improvement in associated dysmenorrhea in about 75% of cases.

Comment: Daflon is a commercial preparation that contains two flavonoids, diosmin and hesperidin. A number of different flavonoids have been shown to improve capillary integrity, which appears to be impaired in some women with idiopathic menorrhagia. Studies conducted a half-century ago found that supplementation with citrus flavonoids in combination with vitamin C was frequently beneficial in the treatment of menorrhagia or metrorrhagia (bleeding between menstrual periods). However, these studies attracted little interest, and this simple treatment is virtually unknown to the conventional medical community. Hopefully, there will be greater interest this time around.

Mukherjee GG, et al. Treatment of abnormal uterine bleeding with micronized flavonoids. Int J Gynaecol Obstet 2005;89:156-157.

One hundred-forty three patients with hypercholesterolemia or combined hyperlipidemia were randomly assigned to receive, in double-blind fashion, sugar cane policosanol (10, 20, 40, or 80 mg/day) or placebo for 12 weeks. In none of the five treatment groups did the mean LDL-cholesterol level decrease more than 10% from baseline. No statistically significant differences between policosanol and placebo were observed with respect to the mean changes in total-, LDL-, or HDL-cholesterol, the ratio of LDL-cholesterol to HDL-cholesterol, or triglyceride levels. A test analyzing dose-dependency yielded nonsignificant results.

Comment: Policosanol is a mixture of long chain (C24 to C34) primary alcohols, originally isolated from sugar cane wax. These long-chain primary alcohols are also found in bee's wax, rice bran, and wheat germ. A number of studies have found that sugar cane policosanol lowers serum cholesterol levels as effectively as various statin drugs. However, all published studies demonstrating a beneficial effect of sugar cane policosanol have been authored by a single research group from Cuba. The results of the present study, as well as those of a similar study using wheat germ policosanol that I cited a few months ago in this column, suggest that policosanol is not an effective treatment for hyperlipidemia.

In my review of the wheat germ policosanol study, I requested feedback from readers about their experiences with policosanol. So far, I have received one correspondence, from a doctor who has observed that sugar cane policosanol, usually in doses of 20-40 mg/day, is very effective for lowering lipid levels.

Berthold HK, et al. Effect of policosanol on lipid levels among patients with hypercholesterolemia or combined hyperlipidemia: a randomized controlled trial. JAMA. 2006;295:2262-2269.

Two hundred forty-eight patients with multinodular goiter who were receiving treatment with thyroxine were studied. Fifty-three of the patients also had Helicobacter pylori-related gastritis and 60 had atrophic gastritis (31 with evidence of H. pylori infection and 29 without such evidence). The daily requirement of thyroxine to maintain a low TSH level (0.05-0.20 mU/L) was 22-34% higher in patients with H. pylori-related gastritis, atrophic gastritis, or both conditions, than in patients without those conditions. In prospective studies, the development of H. pylori infection in 11 patients treated with thyroxine led to an increase in the TSH level (p = 0.002), an effect that was nearly reversed after eradication of H. pylori. In a similar way, omeprazole treatment, which reduces gastric acid secretion, was associated with an increase in the TSH level in all 10 patients treated with thyroxine, an effect that was reversed by an increase in the thyroxine dose by 37%.

Comment: These findings suggest that gastric acid secretion is necessary for effective absorption of thyroxine. Patients who develop conditions that result in reduced acid secretion (such as H. pylori infection or atrophic gastritis) and patients who take antacids or acid-blocking drugs may require an increase in their thyroxine dose to maintain a euthyroid state. Conversely, an increase in gastric acidity (as would result from discontinuation of antacids or acid blocking drugs, from treatment of a hypochlorhydric patient with hydrochloric acid, and possibly from the eradication of H. pylori) may require a decrease in their thyroxine dose. Patients being treated with thyroxine should be monitored more closely during periods in which their gastric acidity is expected to change.

Centanni M, et al. Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N Engl J Med. 2006;354:1787-1795.