I just picked the most recent meta-analysis I could find, which also specifically estimates the dose-response curve. (Since averaging the effect at 400 IU and 4000 IU doesn't make sense.)
> Others have already shared other studies showing no significant effects of Vitamin D intervention.
Yes, and the Ghaemi et al 2024 meta-analysis addresses the methodological problems in those earlier meta-analyses. (For example, they average the effects at vastly varying doses from 400 IU and 4000 IU)
> According your numbers, taking Tylenol would be worse than placebo alone! 0.4 vs 0.7
No, I understand this fine. Taking Tylenol would give you active medication + placebo + time, which is 0.4 + 0.7 + X > *1.1.* Taking open-label placebo is just placebo + time = *0.7* + X.
(Edit: Also, these aren't "my" numbers. They're from a major peer-reviewed study published in Nature, the highest-impact journal. I don't like "hey look at the credentials here", but I bring it up to note I'm not anti-science, see below paragraph)
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Stepping back, I suspect the broader concern you have is you (correctly!) see that supplement/nutrition research is sketchy & full of grifters. And at the current moment, it seems to play into the hands of anti-establishment anti-science types. I agree, and I'll try to edit the tone of the article to avoid that.
That said, there still is some good science (among the crap), and I think the better evidence is accumulating (at least for Vitamin D) that it's on par with traditional antidepressants, possibly more. I agree that much larger trials are required.
Hi, author of the blog post here! Thank you for writing in with your concerns. First:
> Please be very careful when someone tries to tell you that supplements are miraculous and pharmaceutical drugs don’t work at all.
I'll concede I unintentionally gave the tone that one should replace antidepressants with supplements, even though the conclusion specifically writes: "(Don't quit your existing antidepressants if they're net-positive for you!) you may also want to ask your doctor about Amitriptyline, or those other best-effect-size antidepressants."
I have now edited the intro to more explicitly say "you can take these supplements alongside traditional antidepressants! You can stack interventions!"
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> and nobody noticed this massive discrepancy until now?
> Several meta-analyses of epidemiological studies have suggested a positive relationship between vitamin D deficiency and risk of developing depression (Anglin et al., 2013; Ju, Lee, & Jeong, 2013).
> Although some review studies have presented suggestions of a beneficial effect of vitamin D supplementation on depressive symptoms (Anglin et al., 2013; Cheng, Huang, & Huang, 2020; Mikola et al., 2023; Shaffer et al., 2014; Xie et al., 2022), none of these reviews have examined the potential dose-dependent effects of vitamin D supplementation on depressive symptoms to determine the optimum dose of intervention. Some of the available reviews, owing to the limited number of trials and methodological biases, were of low quality (Anglin et al., 2013; Cheng et al., 2020; Li et al., 2014; Shaffer et al., 2014). Considering these uncertainties, we aimed to fill this gap by conducting a systematic review and dose–response meta-analysis of randomized control trials (RCTs) to determine the optimum dose and shape of the effects of vitamin D supplementation on depression and anxiety symptoms in adults regardless of their health status.
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> even common OTC pain meds can have effect sizes lower than 0.4 depending on the study. Have you ever taken Tylenol or Ibuprofen and had a headache or other pain reduced? Well you’ve experience what a drug with a small effect size on paper can do for you.
I must push back: that's an effect of 0.4 plus placebo effect and time.
There's now RCTs of open-label placebos (where subjects are told it's placebo), which show even open-label placebos are still powerful for pain management. So, I stand by 0.4 being a small effect; even if you took a placebo you know to be placebo, you'd feel a noticeable reduction in pain/headache.
> We found a significant overall effect (standardized mean difference = 0.72, 95% Cl 0.39–1.05, p < 0.0001, I2 = 76%)
of OLP.
In other words, if the effect on antidepressants vs placebo is ~0.4, and the effect of a placebo vs no placebo (just time) is ~0.7, that means the majority of the effect of antidepressants & OTC pain meds is due to placebo.
(I don't mean this in an insulting way; the fact that placebo alone has a "large" effect is a big deal, still under-valued, and means something important for how mood/cognition can directly impact physical health!)
Thank you! I relate; I live in Montréal, close to New England, with similar climate. The current UV Index for Montréal is... 0. And the current UV Index for Boston is... 0.6. (1.6 later today)
I can't find a rigorous academic source right now, but the top web results all say we need at least UV Index 3 for our skin to be able to make enough Vitamin D. I guess summer may work for us, in the Montreal/New England area, but other than that, yeah, you and I will need to get Vitamin D from diet and/or supplements. And fish is expensive, so supplements it is.
Hi, I'm the author of the main blog post. Just wanted to say that's a fascinating experience, 160,000 IU a day! I mean, I'm not going to try that, but that's good to hear that 5,000 IU/day for years has been working fine for you. Thanks for sharing!
Hi, author of the blog post here! Thanks for your concern. I do still stand by my claim, since more recent peer-reviewed studies have shown that up-to-10,000 IU is safe. As written in the post:
> McCullough et al 2019 gave over thousands of patients 5,000 to 10,000 IU/day, for seven years, and there were zero cases of serious side effects. This is in line with Billington et al 2020, a 3-year-long double-blinded randomized controlled trial, where they found "the safety profile of vitamin D supplementation is similar for doses of 400, 4000, and 10,000 IU/day." (though "mild hypercalcemia" increased from 3% to 9%. IMHO, that's a small cost for reducing the risk of major depression & suicide.)
So why then does Mayoclinic, etc, all say 4000 IU is the limit? I think because policy is decades behind science (this happened with trans fats), and also policymakers are much more risk-averse. (this is why in California, thanks to Prop 65, up until ~2018, there used to be a warning in every coffeehouse that coffee causes cancer.)
But thanks to your comment, I will edit the intro to note what the official max safe dose is, and that more recent peer-reviewed research shows it's too low!
Hi, author of the blog post here! Thanks for bringing this up -- it wasn't my intention to say one should replace antidepressants with vitamins (the conclusion even says "(Don't quit your existing antidepressants if they're net-positive for you!)", but you're right that the intro may give that impression. I'll edit the intro to say you can stack, not substitute, regular antidepressants.
> many studies in the Vitamin D meta-analysis enrolled patients already taking antidepressants.
Yes, and that's even more encouraging, that there's still effects of Vitamin D on major depression even if already on antidepressants! This suggests we can "stack" the interventions.
Table 1 of the meta-analysis ( https://pmc.ncbi.nlm.nih.gov/articles/PMC11650176/ ) shows the raw sub-group analysis. There were 9 studies on patients using antidepressants, 13 on patients who weren't, the rest were Mixed or Not Reported (...how do 6 studies just not report that?) Anyway,
Effect size of Vit D for people on antidepressants:
−0.54 (−0.85, −0.23)
Effect size of Vit D for people NOT on antidepressants:
−0.28 (−0.40, −0.16)
Both negative. Weirdly, the effect of Vit D seems to be a bit stronger for people on antidepressants, but the difference isn't statistically significant at the p<0.05 level (P subgroup difference is 0.23)
(As for why those effect sizes, -0.54 & -0.28, are lower than what I (and that meta-analysis itself) report, -1.82, that's because the majority of RCTs for any group used far less than 5000 IU. Table 2 in that paper shows the effect (with 95% CI) for various dosages.)
I'll lightly edit my blog post to emphasize stack them, don't substitute. Thanks again for your comment!
Hi, author of the blog post here! Yes thank you for catching this awful typo, it's fixed now! I did write "4000 or 5000 IU of Vitamin D" everywhere else in the article -- main text, conclusion -- just my luck that the one place I mess up is right at the very start.
(Do not take 5000 mg, that's 200,000,000 IU. You'd have to chug dozens of bottles per day)
Hi, author of the blog post here! Thank you for sharing your experience with antidepressants, I'm really glad it worked for you & made your life better.
I did mention the following at the end of the "antidepressants" section, but reading your comment convinced me to move it further up. The intro now reads:
> The "standardised effect size" of antidepressants on depression, vs placebo, is around 0.4. (On average; some people respond much better or much worse.)
Also, I wasn't expecting my article to do well on Hacker News; thank you everyone for the comments & critiques! I'll edit the blog post as I go along, to refine it in response to your comments.
The devs are also running a crowdfunding campaign for this,
with 10% of the donations going to the EFF, Demand Progress, Mozilla, etc:
https://back.nothingtohide.cc
That's a great idea! Perhaps the gamedevs who participated in The Bitcoin Bundle [1] might be the most receptive to the idea of open-sourcing their games.
Not art, but Blender is the biggest example of "buying out for the public" that comes to mind.
Blender used to be proprietary software, and when their company went bankrupt, they crowdfunded 100,000 euros to release their code as open-source. This was a decade ago. Blender is now the most popular open-source 3D animation software today.
Thanks! As for the form, I'm guessing it was because the required email field (to send you your download link) was left unfilled. It's my bad, I didn't make the "please fill in this field" prompt obvious enough. I just left it as the HTML5 form validation default.
Hi, organizer of The Open Bundle here! Thanks for submitting our campaign to HN. We just reached our "public domain release" goal half an hour ago, hopefully this will lead to more indies aiming to earn money by opening their works.
If I recall, if you send someone directly to the discussion page, your vote will not count. It'll register on the counter, but it won't effect your ranking. (I think Reddit does the same thing) This is to protect from mass-voting and spam.
Object.observe() is an upcoming feature for JavaScript, which allows you to add listeners to object's properties changing. With that, you could do the same thing as this library, but without this library. Still, I'm a fan of reactive programming, so thanks for this anyway!
Great point about slacktivism being due of a lower barrier to supporting a cause.
However, I doubt that a higher barrier would cause the "slacktivists" to engage more, rather than just not engage at all anymore.
Maybe one day microdonations (Flattr/CentUp/Gittip) will help lower the barrier to actually donating to a cause. To the point where donating is as easy as hitting a Like button.
Off the top of my head, I can think of 3 ways to provide real-world context for your studies.
The first would be a project-based curriculum. Students get to apply what they learn as soon as they learn it. I remember fondly the Twitter clone I made in Computer Science!
Another way is guest lecturers. In my high school, they would bring in a university professor to lecture once in a while. Students have more confidence when they know the teacher is immersed in the field.
Finally, internships. My internship at Electronic Arts taught me more than just technical skills - it also taught me communication, management, and design. Soft skills not taught in a curriculum.
Having access to digital distractions is just half of why students get bored. The other problem is that the material taught in K-12 schools feels irrelevant, because it is.
As an example, OP brings up art analysis. Done properly, it is a rewarding endeavour. But the kind of art analysis you find being taught by dispassionate high school teachers are of the "The Curtains Were Fucking Blue" variety. And so, students come away thinking that's what all art analysis is: irrelevant.
Students need real-world, meaningful context for what they're learning.
Not contrived word problems or symbolism-searching.