{"id":228,"date":"2014-03-25T19:17:39","date_gmt":"2014-03-25T19:17:39","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=228"},"modified":"2014-03-27T01:55:07","modified_gmt":"2014-03-27T01:55:07","slug":"life-extension-supplements-a-reality-check","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/03\/25\/life-extension-supplements-a-reality-check\/","title":{"rendered":"Life Extension Supplements: A Reality Check"},"content":{"rendered":"<p dir=\"ltr\"><em>In a paper published late last year, a cautious and expert biochemist reports that none of the most popular \u201clife extension supplement\u201d mixes actually extend life span in mice.<\/em><\/p>\n<p>&nbsp;<\/p>\n<p dir=\"ltr\">Stephen Spindler, biochemistry prof at UC Riverside, has been warning us for years that supplements, herbal extracts and nutraceuticals are, on the whole, ineffective for healthy adults, and that some may actually shorten life expectancy. \u00a0Spindler\u2019s lab has done many life extension studies on mice (<a href=\"http:\/\/link.springer.com\/article\/10.1007%2Fs11357-011-9224-6#page-1\">summary<\/a>), almost always with negative results. \u00a0<a href=\"http:\/\/online.liebertpub.com\/doi\/abs\/10.1089\/rej.2012.1386\">One recent report<\/a> included separate life span tests on extracts of blueberry, pomegranate, green and black tea, cinnamon, sesame, curcumin, morin, pycnogenol, quercetin, and taxifolin.<\/p>\n<p dir=\"ltr\">One of the themes in his papers is that caloric restriction is the only thing that works consistently, and that many of the treatments that seem to offer life extension are subtley inducing caloric restriction, (and this goes unreported by the investigators). \u00a0But there are so many substances to test, and each lifespan test in mice is so expensive, that Spindler has suggested gene expression profiles as a shortcut to identifying candidates for further testing.<\/p>\n<p dir=\"ltr\">Another approach is to test many substances at once in a mouse life extension cocktail. \u00a0Another rationale for this kind of testing is that we know that <a href=\"http:\/\/ajcn.nutrition.org\/content\/98\/2\/454.short\">natural fruits and vegetables contribute to a long and healthy life<\/a>, so perhaps it takes a complex combination of nutrients to be effective. \u00a0Late last year, Spindler reported on his experiments, feeding commercial \u201clife extension\u201d mixes to hybrid mice. \u00a0The results are a bracing cold shower for those of us who take a variety of carefully-chosen supplements each day &#8211; and a personal caution to me, since I have recommended supplements on my <a href=\"http:\/\/agingadvice.org\">Aging Advice web page<\/a>. \u00a0[<a href=\"http:\/\/link.springer.com\/article\/10.1007\/s11357-013-9609-9\">Link to Spindler combinations paper<\/a>]<\/p>\n<p>&nbsp;<\/p>\n<p dir=\"ltr\"><strong>Results<\/strong><\/p>\n<p dir=\"ltr\">Seven of the eight graphs of survival time in the paper look like this.<\/p>\n<p dir=\"ltr\"><a href=\"https:\/\/scienceblog.com\/wp-content\/uploads\/sites\/2\/2014\/03\/Spindler-Fig1.png\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-229\" alt=\"Spindler-Fig1\" src=\"https:\/\/scienceblog.com\/wp-content\/uploads\/sites\/2\/2014\/03\/Spindler-Fig1.png\" width=\"339\" height=\"348\" \/><\/a><\/p>\n<p dir=\"ltr\">The mice that ate the supplements and the mice that ate ordinary mouse chow had exactly the same pattern of mortality.<\/p>\n<p dir=\"ltr\">(The agreement between treatment and control is so perfect that, if it were a scientist of less integrity, I would suspect the data had been doctored. \u00a0But in Spindler\u2019s case, I think the consistency of the results bears witness to his expertise in all aspects of mouse husbandry and experimental desgin. \u00a0Clearly, his lab has benefited from a lot of experience, and has adopted methods of caging, feeding, watering, temperature and light control that eliminate a lot of the usual experimental scatter. \u00a0Even choice of the mouse strain was subject to thoughtful analysis.)<\/p>\n<p dir=\"ltr\">The eighth treatment group showed slightly shorted life span.<\/p>\n<p dir=\"ltr\"><a href=\"https:\/\/scienceblog.com\/wp-content\/uploads\/sites\/2\/2014\/03\/Spindler-Fig8.png\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-230\" alt=\"Spindler-Fig8\" src=\"https:\/\/scienceblog.com\/wp-content\/uploads\/sites\/2\/2014\/03\/Spindler-Fig8.png\" width=\"339\" height=\"348\" srcset=\"https:\/\/scienceblog.com\/joshmitteldorf\/wp-content\/uploads\/sites\/2\/2014\/03\/Spindler-Fig8.png 339w, https:\/\/scienceblog.com\/joshmitteldorf\/wp-content\/uploads\/sites\/2\/2014\/03\/Spindler-Fig8-292x300.png 292w\" sizes=\"auto, (max-width: 339px) 100vw, 339px\" \/><\/a><\/p>\n<p>&nbsp;<\/p>\n<blockquote><p>Our results do not support the hypothesis that simple or complex combinations of nutraceuticals, including antioxidants, are effective in delaying the onset or progress of the major causes of death in mice. The results are consistent with epidemiological studies suggesting that dietary supplements are not beneficial and even may be harmful for otherwise healthy individuals. [<a href=\"http:\/\/link.springer.com\/article\/10.1007\/s11357-013-9609-9\">Spindler<\/a>]<\/p><\/blockquote>\n<p>&nbsp;<\/p>\n<p dir=\"ltr\"><strong>What substances were tested?<\/strong><\/p>\n<p dir=\"ltr\">There were eight test groups with different mixtures of supplements, one control group fed only standard mouse chow, and one calorically restricted \u201cpositive control\u201d that got less mouse chow (and lived longer). \u00a0There was some overlap among mixtures of compounds in the eight test groups. \u00a0The list of substances included is long. \u00a0Here are highlights:<\/p>\n<p>&nbsp;<\/p>\n<p dir=\"ltr\">Aspirin<br \/>\nAlpha Lipoic Acid<br \/>\nBlueberry extract<br \/>\nCarnitine<br \/>\nCarnosine<br \/>\nCoQ10 (ubiquinol)<br \/>\nDHEA<br \/>\nGinkgo<br \/>\nGreen tea<br \/>\nMelatonin<br \/>\nMany minerals<br \/>\nN-Acetyl Cysteine<br \/>\nPomegranate extract<br \/>\nQuercetin<br \/>\nResveratrol<br \/>\nSAMe<br \/>\nSilymarin (milk thistle)<br \/>\nVitamin A complex<br \/>\nVarious B vitamins<br \/>\nVitamin C<br \/>\nVitamin D3<br \/>\nVitamin E<br \/>\nVitamin K2<\/p>\n<p>Two of these substances (metformin and melatonin) have a credible history of life extension potential in past experiments with mice. \u00a0Spindler doesn\u2019t comment, and I leave this as an open question. \u00a0There is credible data in humans for two more (<a href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2012\/10\/09\/vitamin-d-and-aspirin-fast-track-to-a-longer-life\/\">vitamin D and aspirin<\/a>), both of which have been shown to lower all-cause mortality. \u00a0I am not aware of rodent life span studies of vitamin D or aspirin, but I trust that one of you, my readers, will point me to a reference.<\/p>\n<p dir=\"ltr\">Notably absent were prescription drugs that have been shown to lengthen mouse life span in the past: deprenyl, metformin, and rapamycin. \u00a0The first two are, in my opinion, suitable for general human use.<\/p>\n<p>&nbsp;<\/p>\n<p dir=\"ltr\"><strong>Fish oil responsible for shortened life span<\/strong><\/p>\n<p dir=\"ltr\">Why did experiment #8 actually shorten life span (by about 9%)? \u00a0Spindler speculates that it might be due to the way mice respond to omega 3 fatty acids (fish oil). \u00a0He cites not-yet published data in which fish oil alone was found to shorten life span. \u00a0Another possibility he mentions is the well-established fact that plant compounds can mimic the effects of mammalian hormones, and that indiscriminate overdoses of plant extracts can throw the metabolism into dysregulation.<\/p>\n<p>&nbsp;<\/p>\n<p dir=\"ltr\"><strong>Caveats: Mice are not humans<\/strong><\/p>\n<p dir=\"ltr\">Some things about aging metabolism in mice are the same as humans, and some are different. \u00a0One principal difference is that aging mice die predominantly of cancer, while aging humans die of cardiovascular disease, cancer, and Alzheimer\u2019s disease. \u00a0Aging mice, like aging humans, are flooded with hormones that dial up inflammation that destroys healthy tissue and heightens risk of cancer [<a href=\"http:\/\/dx.plos.org\/10.1371\/journal.pone.0012940.g005\">ref<\/a>]. \u00a0So the failure of anti-inflammatory ingredients (e.g. omega-3 fats, aspirin) in these mixes to have a life extension effect is particularly puzzling. \u00a0Unlike humans, aging mice do not suffer from short telomeres, so we might hope that telomerase activators (e.g. silymarin, astragalus extracts, ashwagandha, bacopa) would benefit human life span even if they do not help mice.<\/p>\n<p dir=\"ltr\">A partial explanation for the null results is that some of the combinations include anti-oxidant vitamins, which have been shown generally to shorten lifespan. \u00a0This could be counteracting the benefits of some ingredients that might provide benefits on their own. \u00a0Likewise for the fish oil that was included in one of the ineffective combinations.<\/p>\n<p>&nbsp;<\/p>\n<p dir=\"ltr\"><strong>What does this leave us?<\/strong><\/p>\n<p dir=\"ltr\">There is epidemiological evidence for mortality reduction in humans from small doses of NSAIDs (ibuprofen, aspirin) and for large doses of vitamin D.<\/p>\n<p dir=\"ltr\">There is evidence from rodent experiments that melatonin, metformin and deprenyl extend life span. \u00a0There are reports from one lab in Russia that SkQ should be added to this list, but it is not yet commercially available.<\/p>\n<p dir=\"ltr\">There is anecdotal evidence and theoretical support for telomerase activators: \u00a0astragalosides, silymarin, other herbs, carnosine, etc. \u00a0We expect these might work better in humans than in mice, though evidence is yet thin.<\/p>\n<p dir=\"ltr\">Everything else is speculative, and many anti-aging supplements will help some people but not others. \u00a0There is also the disturbing potential for actual harm, as Spindler emphasizes. \u00a0None of us wants to think that the mix of supplements we take might be shaving years off our life expectancies.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>In a paper published late last year, a cautious and expert biochemist reports that none of the most popular \u201clife extension supplement\u201d mixes actually extend life span in mice. &nbsp; Stephen Spindler, biochemistry prof at UC Riverside, has been warning us for years that supplements, herbal extracts and nutraceuticals are, on the whole, ineffective for &#8230; <a title=\"Life Extension Supplements: A Reality Check\" class=\"read-more\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/03\/25\/life-extension-supplements-a-reality-check\/\" aria-label=\"Read more about Life Extension Supplements: A Reality Check\">Read more<\/a><\/p>\n","protected":false},"author":65,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_post_was_ever_published":false},"categories":[1],"tags":[],"class_list":["post-228","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.6 (Yoast SEO v27.6) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>Life Extension Supplements: A Reality Check - Josh Mitteldorf<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. This makes the mechanism challenging to understand and to model. more at http:\\\/\\\/mathforum.org\\\/~josh\",\"sameAs\":[\"http:\\\/\\\/AgingAdvice.org\"],\"url\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/author\\\/joshmitteldorf\\\/\"}]}<\/script>\n<!-- \/ Yoast SEO Premium plugin. -->","yoast_head_json":{"title":"Life Extension Supplements: A Reality Check - Josh Mitteldorf","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/03\/25\/life-extension-supplements-a-reality-check\/","og_locale":"en_US","og_type":"article","og_title":"Life Extension Supplements: A Reality Check","og_description":"In a paper published late last year, a cautious and expert biochemist reports that none of the most popular \u201clife extension supplement\u201d mixes actually extend life span in mice. &nbsp; Stephen Spindler, biochemistry prof at UC Riverside, has been warning us for years that supplements, herbal extracts and nutraceuticals are, on the whole, ineffective for ... 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. 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