Iodine is another critical micronutrient, and iodine deficiency has a profound effect on human health [79,80]. Mild to moderate iodine deficiency has been associated with an extraordinarily high occurrence of hyperthyroidism in at-risk populations [81]. Epidemiological studies have established that the incidence of goiter runs parallel to that of thyroid cancer [82-84]. In a rat model, iodine deficiency has been found to be a more efficient tumor promoter than the carcinogen itself [85].

The relationship between thyroid function and breast physiology was strengthened by observations that reproducible breast dysplasia and neoplasia were obtained in iodine deficiency that was reversible with iodine replacement [86,87]. Breast cancer patients as a group were found to have a lower thyroid function than women having conditions unrelated to breast cancer [88].

It has been pointed out that in the U.S., breast cancer tends to occur in geographical areas associated with iodine deficiency [89]. In contrast, in Japan, where iodine intake levels are higher, a much lower breast cancer incidence is observed [90]. Fibrocystic breast disease, a known risk factor for breast cancer, can largely be prevented by iodine supplementation [91]. In this study, molecular iodine was found to be more effective than iodide, the currently favored form of iodine supplementation. In iodine supplementation studies unrelated to cancer, molecular iodine complexed to lipids was also found to be more effective than iodide [92]. It was also reported that iodolipids formed from iodine in the thyroid gland may play a role in providing proliferative control in breast tissue [93]. Another observation is that in old Pharmacopoeias, for oral iodine administration the molecular form was prescribed [94].

While breast cancer rates in Japan have been comparatively low, they have been increasing recently: this has been associated with the "Westernization" of the country's diet [11]. A study from Spain also established a link between regions of iodine deficiency and breast cancer mortality rates [95]. Traditional Eastern Asian medicine has long used iodine-rich seaweed for cancer treatment [96]. This observation is interesting in light of the fact that in malignant thyroid nodules, the iodine concentration was found to be 15 times lower than in benign nodules [97], demonstrating severe iodine deficiency in the tumor tissue. Recent studies with animal models support the anti-cancer effect of iodine [98,99].

Iodine deficiency has a profound negative effect on the immune system [100]. A significant immune deficiency has been reported among patients with gastric cancer, thyroid cancer and goiter [101]. Iodine was also found to increase immunoglobulin G synthesis in vitro in human lymphocytes [102]. Impaired capacity of immunoglobulin production in active cancer patients has been observed [103], which might be modulated by iodine supplementation. These observations indicate that iodine has a direct effect on the immune system and anticancer defenses.

In 1990, statistics showed that iodine deficiency affected about one-third of the world's population, and despite efforts to correct this problem, it persists. A recent study from South Africa indicated a significant iodine deficiency country-wide [84]. Another study from Switzerland reported that despite more than 80 years of a national iodine supplementation program, only 24% of the participants in the healthy volunteer group reached the WHO recommended level for dietary iodine intake, indicating a significant iodine deficiency among the Swiss [104]. This result was attributed to the growing consumption of manufactured food products deficient in iodine. Although similar data is not available for the United States, a comparable level of development and the high popularity of manufactured foods suggest that the US situation is likely not much different from that in Switzerland.