{"id":1210,"date":"2024-05-07T18:02:12","date_gmt":"2024-05-07T18:02:12","guid":{"rendered":"https:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=1210"},"modified":"2024-05-07T18:02:12","modified_gmt":"2024-05-07T18:02:12","slug":"why-not-spermidine","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2024\/05\/07\/why-not-spermidine\/","title":{"rendered":"Why not Spermidine?"},"content":{"rendered":"

Spermidine is found naturally in many foods. Blood levels decline with age. Supplementation extends lifespan and healthspan in various species, and lowers mortality in human trials. I have been unable to find toxicity data or any downside to spermidine supplementation, except that the effective dosage may be impractical.<\/span><\/p>\n

\u201c<\/span>Consistently across species, extra supply of spermidine prolongs the life span in an autophagy-dependent manner and counteracts age-associated pathologies such as cardiovascular disease, neurodegeneration, and cancer.\u201d <\/span>
\n<\/span>\u2014 Guido Kroemer in <\/span>Science<\/span> [<\/span>2018<\/span><\/a>]\u00a0<\/span><\/em><\/p><\/blockquote>\n

If you haven\u2019t followed <\/span>Guido Kroemer<\/span><\/a>, you\u2019ll find he\u2019s a wellspring of deep biochemical knowledge.\u00a0<\/span><\/p>\n

Many life extension strategies involve hacking the body\u2019s signaling systems, binding to specific proteins like SIRT or TOR. But spermidine is a small molecule, too simple to have specific signaling properties. Compared to even smaller molecules like H<\/span>2<\/span>O<\/span>2<\/span> and NO, it persists in the metabolism long enough to be transported and affect multiple tissues.\u00a0<\/span><\/p>\n

\"\"<\/p>\n

Autophagy is the recycling of damaged organelles (cell parts) and damaged biomolecules, a renewing process that has long been recognized as a necessary process for keeping the body young. Mitochondria are the organelles that generate energy, and ROS are their toxic byproduct. One of the most essential functions of autophagy is the recycling of mitochondria.<\/span><\/p>\n

Fasting triggers autophagy, and this is part of the reason it is good for us. Longo\u2019s <\/span>Fasting-Mimicking Diet<\/span><\/a> was designed to promote autophagy. The life extension and other benefits from spermidine are found to result principally from enhanced autophagy. (The way this is determined is to repeat life extension experiments with an autophagy gene disabled, and it is found that spermidine has no benefit [<\/span>2016<\/span><\/a>].) Spermidine was found to extend lifespan in yeast, worms, flies, and human cell cultures [<\/span>2009<\/span><\/a>].<\/span><\/p>\n

Apoptosis=programmed cell death is an essential function for removing senescent and cancerous cells. <\/span>We need apoptosis, and would be more vulnerable without it, but as we get older, apoptosis develops a \u201chair trigger\u201d, and cells begin to commit suicide when they\u2019re still healthy and useful. Overactive apoptosis is to blame for <\/span>sarcopenia<\/span><\/a> \u2013 the loss of muscle mass with age. Apoptosis is also implicated in the loss of brain cells that leads to<\/span> Alzheimer\u2019s Disease<\/span><\/a>. <\/span>Spermidine <\/span>dials down apoptosis<\/span><\/a>.\u00a0<\/span><\/p>\n

Spermidine is an anti-inflammatory, and there is suggestion from animal models that it could relieve arthritis [<\/span>2016<\/span><\/a>]. This <\/span>study<\/span><\/a> found a stronger benefit for spermine, which is a metabolic product <\/span>downstream of spermidine<\/span><\/a>.<\/span><\/p>\n

Foods with the highest concentrations of spermidine include wheat germ, natto and other soy products, mushrooms, some cheeses, and apples. An ounce of wheat germ or 8 oz of cheese contains 10 mg spermidine. Some of our spermidine comes from the gut microbiome. The probiotic <\/span>Bifidobacterium <\/span><\/i>LKM512 increased blood levels of spermidine in mice.<\/span><\/p>\n

Spermidine dosage is curiously missing from some of the most important studies.\u00a0<\/span><\/p>\n

In the mouse lifespan study that produced the best results [<\/span>2017<\/span><\/a>], mean lifespan was extended by 24%. Spermidine was added to the drinking water of test mice at a concentration of 3mM. Translating to humans is not straightforward, but here\u2019s a rough estimate: If you drank 2 quarts a day of water or other fluids with this concentration of spermidine, you would be getting about 1 gram. To get this from food you would eat 6 pounds of wheat germ daily. The highest-dosage supplement pills I can find have 5 mg, so 1 gram per day = 200 pills. For some other supplements, pills of \u00bd g or a full g are not hard to find. I don\u2019t know if spermidine is intrinsically expensive or if there is another reason that supplement companies gauge the dosage levels so low.<\/span><\/p>\n

There are no human studies based on supplementation, but some authors have tried to correlate mortality with estimates of spermidine intake from (self-reported) food surveys. Again, they report results by dividing the test subjects into three groups, comparing highest and lowest (estimated) spermidine intake without specifying quantities [<\/span>2018<\/span><\/a>]. Mortality was reduced by about 25% in the tercile with highest spermidine intake, corresponding to about 3 years of extra life. Because the correlation is computed based on foods, this result may include confounding errors, as the foods highest in spermidine have other health benefits.\u00a0<\/span><\/p>\n

This Japanese study from <\/span>2012<\/span><\/a> looks for factors that affect longevity across 48 Western countries. Because there are so many variables, the uncertainty is great, but dietary polyamines (including spermidine) stood out as a factor decreasing cardiovascular disease burden (r = -0.355, p = 0.007).\u00a0<\/span><\/p>\n

In elders with mild cognitive impairment, there was an indication of possible memory benefits [<\/span>2018<\/span><\/a>, <\/span>2021<\/span><\/a>]. Two studies suggest benefits for immunosenescence as well [<\/span>2014<\/span><\/a>, <\/span>2015<\/span><\/a>].\u00a0<\/span><\/p>\n

Here\u2019s an excellent short review, also by Kroemer [<\/span>2019<\/span><\/a>] as senior author.\u00a0<\/span><\/p>\n

The bottom line<\/b><\/p>\n

I don\u2019t know why it has taken me so long to discover spermidine, or why it is not more frequently discussed by health gurus and biohackers. This month\u2019s <\/span>Life Extension magazine<\/span><\/a> calls for trials of multiple combined interventions \u2014 an idea which I have advocated since <\/span>2018<\/span><\/a>. Spermidine is on top of their list of substances to try in combinations.<\/span><\/p>\n

I plan to self-experiment with high dosages, based on the very limited data from rodents.<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Spermidine is found naturally in many foods. Blood levels decline with age. Supplementation extends lifespan and healthspan in various species, and lowers mortality in human trials. I have been unable to find toxicity data or any downside to spermidine supplementation, except that the effective dosage may be impractical. \u201cConsistently across species, extra supply of spermidine … Read more<\/a><\/p>\n","protected":false},"author":65,"featured_media":1212,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_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":""},"categories":[1],"tags":[],"class_list":["post-1210","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"yoast_head":"\nWhy not Spermidine? - 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\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2024\/05\/07\/why-not-spermidine\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Why not Spermidine?\" \/>\n<meta property=\"og:description\" content=\"Spermidine is found naturally in many foods. Blood levels decline with age. Supplementation extends lifespan and healthspan in various species, and lowers mortality in human trials. I have been unable to find toxicity data or any downside to spermidine supplementation, except that the effective dosage may be impractical. \u201cConsistently across species, extra supply of spermidine ... 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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. 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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\/"}]}},"jetpack_featured_media_url":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-content\/uploads\/sites\/2\/2024\/05\/spermidine.jpg","jetpack_shortlink":"https:\/\/wp.me\/pgtN8h-jw","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts\/1210","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/users\/65"}],"replies":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/comments?post=1210"}],"version-history":[{"count":0,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts\/1210\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/media\/1212"}],"wp:attachment":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/media?parent=1210"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/categories?post=1210"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/tags?post=1210"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}