X-Message-Number: 27455 Date: Sun, 1 Jan 2006 16:14:32 -0800 (PST) From: Doug Skrecky <> Subject: Life Extension with Zinc/Copper Life Extension With Zinc/Copper By Doug Skrecky Few over-the-counter supplements have been proven to reduce human mortality rates. As a consequence many would-be life-extensionists have adopted a shot-gun approach, where numerous supplements are taken, for which there exists little or no proof of efficacy. The hope is that at least one or two of these supplements may indeed exert a benefit, while the rest at least do no harm. In hopes of improving the current poor signal-to-noise ratio, I'd like to call attention to a study which places a zinc/copper supplement combination in the former category. While this combination appears to reduce mortality, many other supplements are either ineffective, or even detrimental. In the Age-Related Eye Disease Study (AREDS) 4753 healthy persons aged 55 to 81 years were followed for a median of 6.5 years. Of these 534 (11%) died. Some subjects recieved a zinc/copper supplement, some recieved an antioxidant supplement instead, while yet others recieved both types of supplement. The zinc/copper supplement consisted of 80 mg zinc as zinc oxide, and 2 mg of copper as cupric oxide. The antioxidant supplement consisted of 500 mg vitamin C, 400 IU vitamin E, and 15 mg beta carotene. All-cause mortality was increased by 15% by the antioxidant supplement, decreased 28% by zinc/copper, and decreased by 14% by their combination. Thus antioxidants appeared to exert a harmful effect on survival, while zinc/copper offered a more powerful beneficial effect. Cause specific effects of zinc/copper on mortality included a 23% reduction on circulatory system related causes of death, 22% reduction on cancer, and a 46% reduction on all other causes of death. Thus this supplement offered an across-the-board benefit. However due to the small number of deaths (534), the authors caution that this putative mortality benefit of zinc/copper requires further study. (Arch Ophthalmol 2004; 122: 716-726) A dosage of 20 mg zinc has been demonstrated to improve thymic status in aged humans, but at a price of a small reduction in serum copper. (Am J Clin Nutr 1993; 57:566-72) Zinc supplements without additional copper may depress the activity of copper dependant superoxide dismutase in humans. (Free Radical Biology and Medicine 1993;14:95-97) No benefit on mortality was noted for elderly patients given 20 mg zinc and 0.1 mg selenium. (Arch Intern Med 1999;159: 748-754) Note that low levels of serum copper and zinc are both associated with increased mortality. (Am J. of Epidemiology 1988 128(2):352-359) Zinc supplementation has rejuvenated the immune system of old mice, and caused regrowth of their thymus glands. (Int. J. Immunopharmac 1995 17(9):703-718) Treatment of old 18 month old Balb/c mice with either zinc or melatonin increased their remaining lifespan. The 50% survival was 22 months for controls, 29 months for melatonin treated, and 30.5 months for zinc treated. Maximum survival was 30 months for controls, 32 months for melatonin treated, and 33 months for zinc treated. (J. of Neuroimmunology 1998; 86:111-122) Melatonin improves zinc absorption, and this effect may underlay its life-extension effect. (Biological Trace Element Research 2003 96:237-245) However note that a complex supplement comprising vitamin C, vitamin E, rutin, selenium and zinc offered no benefit when given to 23 month old C57BL/6 mice. (Mechanisms of Ageing and Development 1996; 92:227-234) Intriguingly zinc given to klotho mutant mice fed a low phosphate diet suppressed their early mortality. (J. Nutr 2001;131:3182-3188) Journal of Neuroimmunology 1998;86:111-122 Presence of links between zinc and melatonin during the circadian cycle in old mice: effects on thymic endocrine activity and on the survival. Abstract: Links between zinc and melatonin in old melatonin treated mice with a reconstitution of thymic functions have been recently documented. Concomitant increments of the nocturnal peaks of zinc and melatonin, with a synchroization of their circadian patterns, are achieved in old mice after melatonin treatment, A recovery of the nocturnal peaks of thymulin plasma levels and of the number of thymulin-secreting cells with a synchronization of their circadian patterns are also achieved. The existence of significant positive correlations between melatonin and zinc and between melatonin and thymulin or the number of thymulin-secreting cells supports the presence of links between zinc and melatonin also during the circadian cycle with a beneficial effect on thymic functions. The altered circadian pattern of corticosteron in old mice is normalized by melatonin. The existance of inverse correlations between corticosteron and melatonin, between corticosteron and zinc, and between corticosteron and thymulin or the number of thymulin-secreting cells during the whole circadian cycle, suggests the involvement of glucocorticoids pathway in the melatonin thymic reconstitution, via zinc. The presence of an interplay among zinc, melatonin, glucorticoids and thymulin may be, therefore, supported during the circadian cycle. "In vitro" experiments from old thymic explants show a direct action of zinc, rather than melatonin, on thymulin production, further suggesting that the action of melatonin on the thymic efficiency is mediated by the zinc bioavailablity. The beneficial effect of the links between zinc melatonin on thymic functions during the circadian cycle, may be extended to a prolonged survival in aging, where, however zinc may be more involved. 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