Astral Codex Ten

SAMe

6 min read

SAMe

Article

SAMe is a recurring concept in the Astral Codex Ten archive, appearing 3 times across 3 issues between May 25, 2021 and October 26, 2022. The archive places it in contexts such as “SAMe is short for s-adenosyl-methionine-e, a chemical involved in folate and serotonin metabolism”; “Meanwhile, SAMe, which has been shown”; “SAMe for depression”. It most often appears alongside FDA, Zembrin, 2002 meta-analysis by Cochrane Collaboration.

Metadata

  • Category: Concepts
  • Mention count: 3
  • Issue count: 3
  • First seen: May 25, 2021
  • Last seen: October 26, 2022

Appears In

Source Context

Recovered passages from the original issue text. When the raw archive preserved outbound links inside the source passage, they are listed directly under the quote.

Peer Review Request: Depression
May 25, 2021 · Original source
SAMe is short for s-adenosyl-methionine-e, a chemical involved in folate and serotonin metabolism. It comes from a chemical called methionine found in various foods (especially eggs, seeds, and meat), which your body converts into SAMe. Almost every part of folate and serotonin metabolism has been investigated for its role in depression, and SAMe has come out better than most. This meta-analysis has the best summary: SAMe significantly beat placebo in three out of five placebo-controlled studies; in four head-to-head trials against antidepressants, it did about equally well. As always, these studies are weak and susceptible to bias. I am positively predisposed to this substance because my girlfriend has used it successfully against depression for many years, and reports consistently becoming more depressed when she forgets to take it. A low dose is 400-600 mg daily; a high dose is 1200-1600 mg daily; as always, start low and go up slowly, over the course of weeks. This is a reasonable brand.
Inline links: This meta-analysis, This
Although it’s fair to call it a “mental illness” as a heuristic, it isn’t “just” “in your head”. Severe depression sometimes affects the psychomotor system as well, producing unusually slow movements and decreased muscle strength. Some depressed people feel like their limbs “have lead weights tied to them”, and this feeling is “real” – it’s the extra work it takes to maintain a posture despite decreased ability to exert muscle force. It’s linked to decreased efficiency in almost every part of the body, including the immune system, the cardiovascular system, and (especially) the gastrointestinal system. Chronically depressed people live almost a decade less than non-depressed people, and there’s increasing evidence that this isn’t just because they’re too depressed to eat right and exercise, it’s also because the same neurological processes affecting their emotional system are affecting the nerves that regulate the heart, lungs, stomach, etc. The emotional / psychological symptoms of depression are so striking that they trick us into thinking depression is “just” an emotion – but even if you could eliminate every emotional symptom tomorrow, depression would still be a serious disease of dysregulated bodily systems.
Inline links: live almost a decade less, there’s increasing evidence
The research beyond that is low-quality and contradictory. Cochrane Review finds a faint signal that maybe resistance exercise helps more than aerobic exercise, but Doyne et al finds they work about the same, and Pennix et al say that aerobic exercise works better, at least in the elderly. Nobody is really able to confidently demonstrate even simple principles like “more exercise works better than less exercise”, or even that exercise is better than stretching. This is one reason I continue to wonder if the sense of accomplishment and getting outside is as important / more important than the exercise itself.
Inline links: Cochrane Review, Doyne et al, Pennix et al
Link: Troof On Nootropics
May 17, 2022 · Original source
The author of the blog Troof sort of replicated my 2020 nootropics survey. But instead of another survey, they made a recommendation engine. You rated all the nootropics you’d taken, and it compared you to other people and predicted what else you would like. The end result was the same: lots of people providing data on which nootropics they liked. Troof got 1981 subjects - more than twice as many as I did - and here were their results:
Inline links: Troof, replicated, 2020 nootropics survey, recommendation engine
I’m especially concerned by psilocybin microdosing, which ranked 8th of almost 150 interventions. Several double-blind studies have now shown this doesn’t work (eg). Worse, in unblinded studies, it seems to “work” best for the people who most strongly believe it will work, and seems to have whatever effect these people believe it will have. This is most likely a very exciting-sounding intervention that doesn’t work at all, and it was one of the very highest-rated on this survey. Meanwhile, SAMe, which has been shown to work well in RCT after RCT, is one of the lowest-rated.
Inline links: eg, it seems to
Highlights From The Comments On Supplement Labeling
October 26, 2022 · Original source
The supplements I find more interesting are things like melatonin for sleep, ashwagandha or silexan for anxiety, SAMe for depression, or caffeine + theanine for focus. All of these are useful, supported by studies, and good alternatives to medications that some people don’t tolerate well. I’m using mental health examples because that’s the subject I know about, but there are probably examples in other fields too (probiotics for digestive problems).
Inline links: silexan
The first article says “In one assessment, researchers found bacteria in all 138 products they investigated.” I have trouble figuring out how to think about this. I take supplements sometimes. Many of my friends take supplements sometimes. According to studies, 86% of Americans take supplements sometimes. If all supplements are contaminated with bacteria, but basically nobody ever has supplement-bacteria-contamination-related health issues (source: I hear about this with approximately the same frequency I hear about food poisoning from heavily-regulated chain restaurants), doesn’t this demonstrate that whatever bacterial-contamination-standard is being used is meaningless? Don’t approximately 100% of objects contain bacteria? Food? Drinks? The human body? I guess I would want something that explains what’s going on here more before I care about this.
Inline links: studies
So my guess is that taking reputable North American supplements gives you about the same heavy metal risk as spices or juices, and taking Chinese or Ayurvedic supplements can potentially have a much higher risk if you’re not careful. My guess is that taking Ayurvedic supplements that have been processed and Westernized and are produced by Western companies (eg ashwagandha) is fine, but I can’t prove it.