At least 41 in-vitro studies have been conducted on the cytotoxic effects of melatonin against cancer cells.190-194 These studies suggest that a number of cell lines, particularly breast cancer, are inhibited at peak physiological concentrations of melatonin (about 0.1 to 1 nM). Thirteen animal studies reported anticancer effects against a number of different can cers.
studies have indicated that vitamin E doses much greater than 440 I.U. do not greatly increase plasma concentrations, we use a range of 440 to 1,700 I.U. per day as a target dose.
Vitamin E is commonly used at doses of 270 to 530 milligrams daily (about 400 to 800 I.U. per day). A dose of 1 gram per day (about 1,500 I.U.) is considered safe.189 Although vitamin E can lead to some adverse effects, primarily increased risk for bleeding, its use even at high doses appears safe in most healthy humans. For example, in one study oral doses as high as 3.2 grams per day (about 4,800 I.U.) resulted in few side effects.189 We can estimate then that the LOAEL dose is about 4,800 I.U. per day.
Therapeutic dose estimates for alpha-tocopherol and VES are summarized in Table 22.9. The tentative recommended dose is 440 to 1,700 I.U. per day, which is equal to the target dose. In the table, the minimum degree of synergism needed for direct inhibitory effects is listed as variable because oral administration of both may increase alpha-tocopherol plasma concentrations, but only a limited number of cell lines may be inhibited at those concentrations.
For dose calculation, it is not clear if synergistic interactions would allow a lower dose of either compound to be effective. Moderate concentrations of alpha-tocopherol are already present in the plasma (oral administration increases concentrations from the range of 12 to 40 |mM only to 30 to 120 |mM), and so a low dose will probably not greatly affect plasma concentrations or contribute to synergistic effects. A low dose might, however, contribute to indirect anticancer effects.
Twenty-eight human studies have been conducted on melatonin alone or in conjunction with interleukin-2.200-204 Seven were randomized controlled studies, and all reported that melatonin or melatonin plus IL-2 increased the survival of patients as compared to those given supportive care or IL-2 alone.
In addition to the above, a number of reviews on the anticancer effects of melatonin have been published.205-209 Lastly, still other in-vitro, animal, and human studies have demonstrated that melatonin increased the effectiveness or decreased the adverse effects of chemotherapy or radiotherapy. These are discussed in Chapter 23.
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