Melatonin

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Animal studies have reported that at doses applicable to humans, or larger ones, melatonin caused an antioxi-dant effect and protected normal cells from the adverse effects of chemotherapy drugs. At the same time, mela-tonin treatment did not reduce the antitumor activity of chemotherapy drugs, even at high doses that would have produced a profound antioxidant effect.

• Oral administration of melatonin (at about 48 milligrams per day, as scaled to humans) improved the antitumor activity of doxorubicin in mice with transplanted Ehrlich ascites cancer cells. Melatonin also improved the antioxidant status of the heart.14

• Oral administration of melatonin (at about 20 milligrams per day, as scaled to humans) reduced damage to auditory neurons caused by cisplatin in rats.193

• Intraperitoneal administration of 4 mg/kg melatonin reduced oxidative damage in the heart induced by doxorubicin treatment in mice and decreased mortality after doxorubicin treatment.17 The equivalent human oral dose is about 300 milligrams.

• Subcutaneous administration of 2 mg/kg melatonin reduced oxidative damage in the liver induced by doxorubicin treatment in mice.194 The equivalent human oral dose is about 120 milligrams.

• Subcutaneous administration of 10 mg/kg melatonin reduced mortality caused by doxorubicin and prevented oxidative damage from it in mice with transplanted lymphoma cells. The antitumor activity of doxorubicin was not reduced by melatonin treat-ment.195 The equivalent human oral dose is about 580 milligrams.

• Subcutaneous administration of 5 mg/kg melatonin reduced genetic damage of normal cells induced by N-nitrosomethylurea, cyclophosphamide, and di-methylhydrazine in mice. The antitumor effects of these drugs in mice with transplanted Ehrlich carcinoma cells were not diminished by melatonin treat-ment.196 The equivalent human oral dose is about 290 milligrams.

As with the animal studies, most human studies also indicated that melatonin acted as an antioxidant and reduced the adverse effects of chemotherapy without lessening its antitumor actions:

• In a randomized, nonblinded study on 250 patients with different advanced metastatic cancers receiving combination chemotherapy, those who also took melatonin (at 20 milligrams per day, orally) showed fewer adverse effects, particularly less myelosup-pression, neuropathy, and heart toxicity. One-year survival was increased in the group receiving mela-tonin (51 percent versus 23 percent).197

• In a randomized, nonblinded study on 80 patients with different metastatic cancers receiving combination chemotherapy, those who received melatonin (at 20 milligrams per day, orally) showed fewer adverse effects, particularly less myelosuppression and neu ropathy. The incidence of hair loss and vomiting was not affected.198

• In a randomized, nonblinded study on 70 patients with advanced non-small-cell lung cancer treated with cisplatin and etoposide, the addition of melatonin (at 20 milligrams per day, orally) increased the one-year survival as compared to those getting chemotherapy only (44 percent versus 19 percent, respectively). The adverse effects of drug treatment, particularly myelosuppression, neuropathy, and ca-chexia, were reduced in the melatonin group.199

• In a phase II study, the addition of melatonin (at 20 milligrams per day, orally) to treatment with epirubi-cin appeared to reduce drug-induced thrombocyto-penia.200

In contrast to the above, a randomized, double-blind study on 20 patients with advanced lung cancer receiving carboplatin and etoposide reported that those who received melatonin (at 40 milligrams per day, orally) did not experience reduced myelotoxic effects.201

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