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From the Townsend Letter for Doctors & Patients
November 2004

Literature Review and Comment
by Alan R. Gaby, MD

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Iodine treatment of fibrocystic breast disease
One hundred-eight women with fibrocystic breast disease were treated with a preparation containing molecular (diatomic elemental) iodine at a dose of 0.08 mg per kg of body weight per day orally for nine months. Ninety-eight percent of the women were pain-free by the end of the study and objective improvement was seen in 71.8% of cases. Sixty-five percent of the women had a reduction in breast size coincident with clinical improvement. In a larger series of women (n = 1,365) treated with molecular iodine, side effects (usually minor) occurred in 10.9% of cases; these included acne, nausea, diarrhea, hair thinning, hyperthyroidism (0.1% incidence), hypothyroidism (0.3% incidence), skin rash, headache, or transient increase in breast pain (5.7% incidence).

Two other groups of women were treated with Lugo's solution (a preparation containing 95% sodium iodide and 5% free iodine) and iodized casein, respectively. The response rate with Lugo's solution was 70%, and with iodized casein was 40%. Molecular iodine was associated with a lower incidence of thyroid dysfunction than the other preparations.

Comment: Fibrocystic breast disease is one of the most common health problems in women. Although the symptoms are frequently minor, some women experience debilitating pain and discomfort. Treatments that are often effective include complete avoidance of dietary caffeine and other methylxanthines and supplementation with 400 to 800 IU per day of vitamin E. There are anecdotal reports that thiamine supplementation (100 mg per day) is also beneficial.

For women who do not respond to these treatments, oral iodine preparations are an important option. The molecular iodine used in the current study is not commercially available, but a compounding pharmacist should be able to make a similar preparation. Lugo's solution is readily available, but it has a lower success rate and causes a higher incidence thyroid dysfunction than does molecular iodine. Thyroid function should be monitored periodically in people taking pharmacological doses of iodine or iodides. Side effects may include metallic taste, excessive salivation, runny nose, and skin rash.

Ghent WR, et al. Iodine replacement in fibrocystic disease of the breast.
Can J Surg 1993;36:453–460.

Indole-3-carbinol for cervical intraepithelial neoplasia
Twenty-seven women with biopsy-proven cervical intraepithelial neoplasia (CIN) classes II or III were randomly assigned to receive, in double-blind fashion, indole-3-carbinol (I-3-C; 200 or 400 mg/day) or placebo orally for 12 weeks. None of the 10 patients in the placebo group had a complete regression of CIN. In contrast, 4 of 8 patients receiving 200 mg/day of I-3-C and 4 of 9 receiving 400 mg/day had a complete regression of CIN after 12 weeks of treatment. In all, 47% of the women receiving I-3-C reverted to normal cervical cytology.

Comment: I-3-C is a compound found in cruciferous vegetables (e.g., broccoli, cabbage, cauliflower, and Brussels sprouts). It has been shown to have anti-cancer activity in animals, possibly by inducing hepatic P450 enzymes that are involved in the detoxification of carcinogens. I-3-C also promotes the metabolism of endogenous estrogens to non-carcinogenic metabolites and may, therefore, be capable of preventing the development of estrogen-dependent cancers. The lower dose of I-3-C used in the present study (200 mg/day) can be obtained by eating about 200 g (7 ounces) of raw cabbage or Brussels sprouts per day.

It has been claimed that diindolylmethane (DIM), a compound that is formed in the stomach from the metabolism of I-3-C, is preferable to I-3-C itself as a therapeutic agent. Most of these claims have come from individuals who appear to have a financial interest in the sale of DIM, and the scientific validity of their statements is difficult to evaluate. Until clinical studies demonstrate the effectiveness of DIM, I will continue to prefer I-3-C for the prevention and treatment of CIN and cervical dysplasia.

Bell MC, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN.
Gynecol Oncol 2000;78:123–129.

Female infertility: consider thyroid hormone
Forty-two women with idiopathic infertility of 1 to 12 years' duration were treated empirically with desiccated thyroid. The initial dose was 1 grain per day; for patients who did not respond, the dose was gradually increased, as tolerated. Twenty-eight similar patients received a placebo. Ten women (23.8%) became pregnant after 1 to 12 months of thyroid therapy, compared with 10.7% of those receiving placebo. Although this difference was not statistically significant, the response rate was more than double in the active-treatment group than in the placebo group.

Comment: Hypothyroidism is a known reversible cause of infertility. Most doctors rely on laboratory tests to diagnose hypothyroidism, but there is a considerable amount of anecdotal evidence that standard thyroid-function tests fail to detect a large proportion of cases of clinical hypothyroidism (Gaby AR. "Sub-laboratory" hypothyroidism and the empirical use of Armour thyroid. Altern Med Rev 2004;9:157–179.). I have seen many women with signs and symptoms suggestive of hypothyroidism (e.g., fatigue, depression, cold extremities, dry skin, constipation, thinning hair, menstrual irregularities, delayed Achilles tendon reflexes) who were treated with thyroid hormone empirically despite having normal laboratory tests. It was not uncommon to see pregnancies rapidly ensue in women who previously had been unable to conceive. Thyroid hormone should not be used indiscriminately, but a therapeutic trial for infertile women with clinical evidence of hypothyroidism is not unreasonable.

Thyroid treatment should not be discontinued during pregnancy, as doing so may increase the risk of a miscarriage. If anything, thyroid hormone requirements increase during pregnancy. On the other hand, the use of excessive doses of thyroid hormone during pregnancy may also increase the risk of miscarriage (
JAMA 2004;292:691–5), so clinical status should be monitored carefully.

Buxton CL, Herrmann WL. Effect of thyroid therapy on menstrual disorders and sterility.
JAMA 1954;155:1035–1039.

A score bait
Forty-two healthy young adults (mean age, 24.4 years) with a current sexual partner were randomly assigned to receive, in double-blind fashion, 3,000 mg/day of vitamin C or placebo for 2 weeks. Among women, the frequency of sexual intercourse during the study was significantly greater in the vitamin C group than in the placebo group (mean, 10.3 vs. 3.7 episodes per month; 178% increase; p = 0.03). Vitamin C had no significant effect in men (mean episodes per month: vitamin C, 5.9; placebo, 6.3). The increase in intercourse frequency occurred only among non-cohabitants, whereas in cohabitants, vitamin C supplementation was associated with a nonsignificant decrease in frequency. The vitamin C group also experienced a decrease (improvement) in Beck Depression scores, whereas no change was seen in the placebo group.

Comment: Supplementation with vitamin C led to an increase in the frequency of sexual intercourse among women not living with their sexual partner. The specificity of the effect to that subset of the study population suggests that vitamin C acts on the brain in a way that reduces inhibitions. Previous studies have shown that administration of vitamin C decreases reactions to stress and improves approach anxiety, effects which may influence sexual behavior and mood.

Brody S. High-dose ascorbic acid increases intercourse frequency and improves mood: a randomized controlled clinical trial.
Biol Psychiatry 2002;52:371–374.

Nuts for your gallbladder
The association between nut intake (peanuts, other nuts, and peanut butter) and cholecystectomy was examined prospectively in 80,718 women participating in the Nurses' Health Study who were 30–55 years old in 1980 and had no history of gallstones. During a mean follow-up period of 17.3 years, 7,831 cholecystectomies were performed. After adjustment for age and other known or suspected risk factors, women who consumed five or more ounces of nuts per week had a 25% lower risk of cholecystectomy than women who never ate nuts or who ate less than one ounce per month (p for trend < 0.0001). Further adjustment for fat consumption (saturated fat, trans fat, polyunsaturated fat, and monounsaturated fat) did not materially alter the findings. In analyses examining consumption of peanuts and other nuts separately, both were associated with a lower risk of cholecystectomy.

Comment: These results indicate that frequent nut consumption is associated with a reduced risk of gallbladder disease requiring cholecystectomy. Other studies have shown that eating nuts can help control high blood pressure, reduce serum cholesterol, and lower the risk of heart disease. While nuts are high in fat, intervention studies have shown that incorporating nuts into the diet has little or no effect on body weight. There is now strong evidence that nuts should be considered as an important component of a health-promoting diet.

Tsai CJ, et al. Frequent nut consumption and decreased risk of cholecystectomy in women.
Am J Clin Nutr 2004;80:76–81.

Calendula prevents radiation-induced dermatitis
Two hundred fifty-four patients receiving postoperative radiation therapy for breast cancer were randomly assigned, in single-blind fashion, to apply topically either trolamine (triethanolamine salicylate; considered by many to be the treatment of choice) or Calendula officinalis (Pommade au Calendula par Digestion; Boiron Ltd, Levallois-Perret, France) ointment on the irradiated fields after each session. Treatment was begun after the first radiation session and was applied twice a day or more, depending on the occurrence of dermatitis and pain. The incidence of acute dermatitis of grade 2 or higher was significantly lower (41% v 63%; p < 0.001) with calendula than with trolamine. Compared with trolamine, calendula was associated with fewer interruptions of radiotherapy because of skin toxicity (0 vs. 12 patients) and significantly less radiation-induced pain (p = 0.03). Calendula was more difficult to apply, but overall satisfaction with its use was greater than with trolamine.

Comment: Acute dermatitis is a common side effect of radiation therapy. Calendula is a common garden plant in North America and Europe. Its flowers have been used traditionally as a topical soothing agent, to treat minor burns and eczema and to promote wound healing. The results of the present study indicate that topical Calendula officinalis is effective for the prevention of acute dermatitis in patients undergoing postoperative irradiation for breast cancer.

Pommier P, et al. Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer.
J Clin Oncol 2004;22:1447–1453.

Pesticides: less is more
Tadpoles of four species of frogs were exposed for 30 days at early and late developmental stages to low concentrations of the pesticide atrazine (3, 30, or 100 ppb; the U.S. Environmental Protection Agency drinking water standard is 3 ppb). Survival was significantly lower for all animals exposed to 3 ppb, compared with either 30 or 100 ppb, except for the late stages of two species.

Comment: Atrazine is the most widely used pesticide in the United States. The results of the present study indicate that, within a certain dosage range, lower concentrations of this chemical are more toxic than higher concentrations. This pattern is characteristic of many endocrine-disrupting compounds.

Scientists often disregard studies that demonstrate a toxic effect of a chemical at low doses, but no toxic effect at high doses. One should not assume, however, the effects of toxic chemicals always increase with increasing levels of exposure. Many chemicals function as catalysts at low concentrations, but become inhibitors at higher concentrations. Some compounds influence one biochemical pathway when present at a low concentration and a different pathway when present at a higher concentration. The results of the present study demonstrate the importance of evaluating the effect of toxic substances at realistic concentrations and at various developmental stages.

Storrs SI, et al. Survivorship patterns of larval amphibians exposed to low concentrations of atrazine. Environ Health Perspect 2004;112:1054–1057.
See also: Kon SH. Underestimation of chronic toxicities of food additives and chemicals: the bias of a phantom rule. Med Hypotheses 1978;4:324–339.

Let your food be your medicine
Thirty-eight patients undergoing cardiac surgery who would be receiving oral furosemide postoperatively were randomly assigned to consume potassium-rich foods (diet) or potassium chloride (KCl) pills (medication). The standard KCl dose was equivalent to half the furosemide dose per day (for example, 60 mg/day of furosemide would require 30 mEq/day of supplemental KCl). Patients in the diet group chose their potassium-rich foods from a list that was provided. If a patient's serum potassium level fell below 3.8 mEq/L, the potassium dose was increased to 75% of the furosemide dose. The mean serum potassium concentration on postoperative days 3 and 4 did not differ significantly between groups. The mean length of hospital stay was significantly lower in the diet group than in the medication group (5.0 vs. 6.3 days; p = 0.03). The reason for that reduction was not apparent, and it did not appear to be due to a decrease in the number of gastrointestinal side effects. When asked their preference for method of supplementation, 79% of patients preferred the diet method.

Comment: Potassium supplementation is often necessary for patients treated with thiazide or loop diuretics. Prescription potassium preparations contain highly concentrated potassium salts, which can cause gastrointestinal side effects including gastric ulceration. High-potassium foods are better tolerated than potassium medication (particularly when the patient is given a range of food choices), and they also provide many other beneficial nutrients.


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