Vitamin D and Omega-3 are the two supplements that consistently appear to be super powerful in small studies and then fail to do anything significant at all in larger studies.

Pause for a moment and consider the mere plausibility of the claims in the first few paragraphs: The effect size for antidepressants is 0.4, but the effect size for Vitamin D is 1.8? Are we to believe that Vitamin D supplements have an effect size 4.5X larger than antidepressant drugs, and nobody noticed this massive discrepancy until now?

Effect size is also a favorite metric in this vein of supplement-over-pharma writing because it’s so commonly misunderstood and it’s so easy to find small supplement studies that have outlier effect sizes.

To put it in context, 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.

Please be very careful when someone tries to tell you that supplements are miraculous and pharmaceutical drugs don’t work at all. I know too many people who delayed trialing SSRIs for years due to internet driven fears and lost many years of their lives to depression based on content like this. People with cabinets full of dozens of supplement bottles that were chosen based on studies, too. Then they finally decided to try real antidepressant medications and wished they’d done it sooner.

As much as I wish we could all just cure depression by taking a simple Vitamin D supplement that has 4.5X higher effect size than antidepressant drugs, this claim just isn’t passable.

Because it's common to hate on antidepressants, I've always personally had a bias against them.

For the past 15-20 years, november thru february are basically a writeoff due for me due to seasonal affective disorder. Cold showers, exercise, no alcohol, strict sleeping rituals. Vitamin d. I can still sleep 11 hours and feel like reheated cat shit.

Enter citalopram. "It will take up to six weeks to dial in" they said. Within four days I felt like the inside of my head was designed by Apple in their glory days. My mind became an orderly, well lit, tastefully designed space... instead of a dimly lit crack den. I'm more emotionally available, no longer tired, less cranky. I felt cozy. I could cry with joy because I could finally understand emotionally why people like the Christmas season.

I won the SSRI lottery I guess, the side effect are sweaty feet, vivid dreams and a dry mouth. That's all.

This just goes to show that for me, they're extremely effective.

Please do not take 5000mg/day of Vitamin D. The author confuses IU and mg which is very dangerous.

Be careful - many studies in the Vitamin D meta-analysis *enrolled patients already taking antidepressants.* [1] Reporting effect sizes without specifying "on which population?" is misleading.

(As an aside, Cohen would be the person not to tell you to assign qualitative values to effect sizes. They are as arbitrary as any other threshold used by working statisticians.)

[1] https://www.cambridge.org/core/journals/psychological-medici...

EDIT – that is, please don't draw the conclusion that you can substitute supplements for antidepressants. The meta-analyses don't seem designed to examine that hypothesis, and I doubt anyone would ever participate in a such a trial. In general (and as a working biostatistician), I would be very, very, very cautious applying estimates of average effect to myself, you, or any other individual person in a field as murky as psychiatry. That's why even the stingiest American health insurance plans still have an incredibly large range of antidepressants in their formularies.

I saw a thing from HealthyGamerGG youtube[1] that he said one of the things about depression is that it causes/influences one to avoid the things that would make their life less depressing.

eg just to paint the picture: you're depressed so you don't get out of bed, therefore you don't go do your workout, therefore you lack endorphins and look in the mirror and see squishy, you're sad about how squishy you are and so you get more depressed. You're more depressed so you also don't do your dishes, when you do get out of bed you are depressed you feel like a slob and you're squishy, so you get more depressed...

Whereas adding anti-depressants, and other virtuous cycle things like vitD/O3, exercise et al. Give the boost necessary to _make your life less depressing_ ...

So if you know someone who's depressed, it might be helpful to help them make their life less depressing too. (in addition to all the best medical advice!)

[1]- he's a real Dr... Dr. Alok Kanojia (Dr. K), a Harvard-trained psychiatrist (MD, MPH) specializing in modern mental health

I found this to be the case. Tried Sertraline for a while, gave me headaches and made me feel sick. Then as part of a new gym plan, started taking Omega 3+VitD daily, and I just felt a sense of calm and peace after a few weeks. The massive uptick in exercise probably also helped. I also felt quite an extreme uptick because I was a vegan for 10 years, and found out I had basically zero Omega 3 in my blood. I suspect one of the main reasons my mental health declined was due to the lack of Omega 3.

Disclaimer, not saying vegans should stop being vegans, just make sure you find a good supplement, and make sure you understand the difference between EPA/DHA Omega 3.

With depression it is important to find the cause of it.

You might be depressed because you life objectively sucks. Then you symptoms are good and healthy and a signal to make changes in your circumstances.

You might actually have a good life but still feel depressed because there is a chemical imbalance in your brain. (Very simplified). That is when drugs come in.

It might be just a seasonal thing and you need to go outside more and take some supplements.

You might have some other undiagnosed issue. You might have ADHD, autism and other things that cause you to struggle and develop depression as a side effect.

So find out what works and what doesn't work for you.

> A 2014 systematic review concluded that vitamin D supplementation does not reduce depressive symptoms overall but may have a moderate benefit for patients with clinically significant depression, though more high-quality studies were determined to be needed.

https://en.wikipedia.org/wiki/Vitamin_D#Depression

The first thing I would do in case of depression is to make sure that the patient's energy levels are good and that mitochondria and other energy-related biochem phenomena work as expected.

I know first-hand that low energy-levels and lacking energy production mechanically lead to depression.

Also, look at how people (children also) experience the world and their relationships and their stresses when they are tired (or even just hungry) compared to when they are fit...

Fix those, and the depression might be gone.

This is not bashing against anti-depressants, they play their role to. But in some cases, energy-management is key.

Can I just add: In addition to this, if you struggle with anxiety or have some sort of ADHD, then try cutting out caffeine entirely. Not just switching to "decaf" (which isn't), but cutting out tea and coffee, and switching to an alternative like Barleycup.

Doing this has had a massive positive effect for me, and combined with decent nutrition and daily exercise, has been wonderful.

At this point, I mostly avoid prescribed medications and don't take very many things at all regularly. Mostly because I've had some of the worst interpretations of the side effects of most medications I've ever been on. These include hospitalizations and side effects I'm still dealing with years after (looking at you Trulicity/Ozempic)...

I'm usually able to reason or force my way through depression and the like, but have had a few deep bouts in my life. The medications have ranged from ineffective to building a tolerance quickly, to just plain worse than the symptoms being treated. Nothing like missing your highway exit multiple times back and forth because you get lost "in" the drive on medication, or having 140 browser tabs open and losing 5 hours of work time.

Everyone is different. I am amazed at how much western society has so many hormonal issues that come down to the lack of quality or appropriate fatty acid intake and a lack of something as simple as more outdoor/sun time. I think the "low fat/cholesterol" advice for most of the past half century combined with the increase in snacking and junk foods have been massive disservices to humanity as a whole. I wouldn't be surprised if some of the effects are multi-generational in the making either.

My physician prescribed Vitamins D and B12, so a quality Omega 3 is the only supplement I currently purchase.

After an absurd amount of trial and error with every over-the-counter, trendy supplement over the last couple of decades (and lord only knows how much money), these are the only ones that seem to make a subjective difference on my quality of life and an objective difference in my bloodwork.

can vouch for a diet high in fatty fish along with supplementation of D3 + cofactors (K2, A, magnesium, zinc, copper, boron). sample size of one but noticeably improves mood and energy levels.

recent evidence [0] suggests there's not much of a link between serotonin and depression, and therefore the effects of SSRIs are either placebo or an as of yet unexplained mechanism of action. IMHO it seems much more likely that modern lifestyles (excessive screen time, poor diet, lack of socialization, no connection to nature, no spirituality, etc) have more of an effect than serotonin levels.

[0] https://pubmed.ncbi.nlm.nih.gov/35854107/

To many people without relevant expertise give medical advice online.

I remember a similar case with levelsio who was advocating people to take melatonin and discussing how much grams is good vs bad. When I said that people shouldn't take medical device from someone who was successful in building web apps, he blocked me.

And better than taking pills for the former, add hemp hearts or flax seeds to your cereal. One serving of hemp hearts has 10 grams of protein and 12 grams of Omegas 3 and 6. Flax seeds are lower in protein but an even better source of Omega 3 in particular.

Coincidence? "Vitamin D is currently the only Essential Vitamin or Mineral which appears to have deficiency rates at a similar level to Magnesium"

https://examine.com/supplements/magnesium/research/#nutrient

Dai (2018): Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial https://pubmed.ncbi.nlm.nih.gov/30541089/ "Our findings suggest that optimal magnesium status may be important for optimizing 25(OH)D status. "

So it might well be that general deficiency in Vitamin D is caused by the deficiency in magnesium status. This would also be an explanation why we see Vitamin D deficiency in sunny Africa: https://theconversation.com/think-vitamin-d-deficiency-is-no...

Confusing mg and IU units up front really do NOT inspire confidence on the topic and conclusion as a whole.

I can only provide anecdotical evidence, which is ... not evidence, really.

Within my peer group of people on the spectrum (which very often comes with a depression, which is logical) we've discussed Vitamin D studies for years. And multiple of us decided to give it a try for a couple of months. And neither those who tried it INSTEAD of an SSRI, nor those that took both (SSRI + D) could report any measurable difference.

I have a theory on why is that: It is known that low levels of Vitamin D is one likely cause for depression - in Northern Europe, where during winter time people do not get enough sunlight, that correlates very clearly with the suffering of depression.

But potentially it simply does not work the other way round: I moved to near the equator, and I therefore basically have sunlight shining out of my butt, but still am depressed. It makes sense that in this case Vitamin D makes no difference at all.

In summary my theory would be: Vitamin D only has an effect on a depression that was caused by a lack of Vitamin D.

Super interesting, just sad that Omega-3 supplements are one of the main drivers of unsustainable Krill overfishing https://seashepherd.org/2025/02/25/protecting-the-oceans-vit...

Why does this keep popping up?

"Evidence does not support the use of vitamin D supplementation for the prevention of cancer, respiratory infections or rheumatoid arthritis. Similarly, evidence does not support vitamin D supplementation for the treatment of multiple sclerosis and rheumatoid arthritis or for improving depression/mental well-being."

https://pmc.ncbi.nlm.nih.gov/articles/PMC4907952/#:~:text=Bo...

The only problem here is that "going from an F to a C in mental health" is vastly different than "going from a C to an A." It's very well known and well documented that antidepressants have very little effect on mild depression compared to say, exercise, but that F grade of depression tends to be a different beast with different causes.

That's not to suggest that exercise etc isn't great, just that society has come a long way in destigmatizing mental health and just being like "oh just take fish oil" to someone dealing with that kind of depression, either through shitty genes or childhood trauma or whatever, can be really harmful.

Anecdotally, I've been taking a 5,000 IU vitamin E supplement this winter. Seattle area, indoor desk job, I am a vampire. It does seem to help, I would rate it as going from a C to a B grade. I'd prefer not to use antidepressant medications to fix a problem that for me is mostly caused by living at a different latitude than I grew up in.

Do be aware that not all vitamin E supplements actually contain the dosage that they are labeled at, and that inclues both no-name brands and some big name brands. I'm having trouble finding a good reference on google due to AI and SEO pollution. But I recall Nature Made was labelled accurately and that is what I buy.

My wife on the other hand has struggled with life-long anxiety/depression even when living in Atlanta. For her a fairly low dose of lexapro enables her to live her life like a normal person. We wish we could get her mother to give it a shot for a few weeks, as she now can see a lot of similarities in both their personality traits that were affected by a life of untreated anxiety.

We also have cat that would probably have been put down for fear-biting of people and attacking our mild and mellow dog until we got his aggression under control with kitty prozac. I kid you not, it's a transdermal fluoxetine cream we put in his ear each day. Without the constant anxiety stimulus in the way, his real personality came through and he is actually very sweet. To me at least. Still bites my wife, but not hard anymore, just enough to keep her alert.

Most commonly from lanolin, a grease extracted from sheep's wool.

It's processed into (7-DHC), the same compound in human skin.

7-DHC is bombarded with UV light, triggering a chemical reaction that creates Vitamin D3.

Vitamin D toxicity is absolutely real, causes hypercalcemia, and can occur even at the 4,000 IU dose. I would really recommend you be getting regular bloodwork done if you go beyond that. Here’s a fun podcast on a case study. https://www.barbellmedicine.com/podcast/episodes/episode-381...

One flaw in this analysis is that the source he cites for antidepressant effectiveness didn't include tranylcypromine (or any MAOI class drugs), which the STAR-D trial found was one of the most effective antidepressants.

(The STAR-D had a cumulative remission rate of 67%, I don't know how to convert that to the format he used)

Otherwise I agree that vit D and omega 3 are underrated for depression, it would be interesting to see if they have a cumulative effect with antidepressants.

The hate on antidepressants is not because they're not effective, but rather that they're abused by psychiatrists. Ideally, a professional will prescribe them as a necessary helper to becoming (more) mentally healthy whilst tackling the root cause. Most of the time however, it's more of a "here, take these indefinitely".

It's like if we took sleeping pills every time we had trouble sleeping. Having said that, I just realised I have the impression that's exactly what people do in the USA?

> I won the SSRI lottery I guess,

From reading internet comments you’d think so, but your experience is more typical than anything.

Depression is deceptively common. As a consequence, SSRI use over a lifetime is also more common than most would assume. Any drug will come with negative side effects for some portion of its users. Multiply that by the high number of people who have ever taken an SSRI and it starts to become obvious why there are so many Internet anecdotes about SSRIs not working.

Meanwhile, most people who take SSRIs successfully aren’t going around and advertising the fact that they’re on psychiatric medications. There is less stigma now than there was in the past, but it’s still not something most people like to broadcast to the world. For patients on long term SSRIs in stable states, the SSRI is just a routine thing they take in the background and don’t really think about. There’s no reason for it to come up in conversation.

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.

“God, I see what you’re doing for others, and I want that for me.”

I had a very similar experience, except it killed my libido, so I chose to endure the suffering of Winter rather than live with emotional numbness.

Still, I strongly recommend it for people flirting with the abyss. It was life-changing for me while I was raising an autistic 2yo during the pandemic.

I had disk issues in my lumbar spine that caused nearly unbearable pain and terrible quality of life. Tried everything: PT, OTC painkillers, epidurals, massage, nothing worked. Was prescribed pragabalin and duloxotine. Duloxotine is an SNRI that also treats nerve pain. That combination helped some but I was sleeping 11+ hours per day and generally felt like my head was in a complete fog, was pretty much useless with work. I had been trying to avoid surgery but finally had 2 procedures in 2024 that helped immensely. Weaning off those 2 drugs was no fun: sweating constantly, anxious, headaches for about 2 weeks. Extremely happy I went the surgery route and stopped those meds. I can't imagine living day to day feeling like that.

It takes a 10 min talk with a doctor to get antidepressants around here. Perhaps a test which looks like multiple choice score of symptoms with some weights.

I had an old gf receive two different drugs each with terrible side effects. To me it looked as poison.

I decided that I would rather hurt myself myself than fuck with my brain chemistry this way.

During the dark northern Winters I lack vitamin D (your doctor can measure this using a blood test). The symptoms are some physical issues and probably something that can be described as light depression which goes away if I remember to take the vitamins.

We are all different. Some people might need anti-depressants. I just need some vitamins.

SSRIs saved my life. No exaggeration. They might be overprescribed, only effective is some individuals, and they certainly have their share of side effects, but they're still the gold standard treatment for clinical depression and anxiety.

If a drug has an 1% chance of 100% effect, it will look pretty weak in those studies.

IMO it's pretty clear that depression is a symptom of many independent issues, so it's really lame that we don't have a more accurate way of diagnosing it.

Similar story here but for ADHD and Atomoxetine.

I finally went and got diagnosed at age 46 for what had been an childhood-onset issue in retrospect. All the signs were there: inability to start work until enough challenge or novelty or a state of crisis had come about, etc. When I spoke to friends about considering treatment, they said they thought of me as a hyperfocus kind of person. But they didn't see how many support systems I had put in place to function normally, how I saw others around me just doing things while I had to work myself up to start and then keep checking and double-checking for the silly inattentive mistakes I knew from experience I would keep making.

I've had a meditation practice for a long time and it has helped with anxiety but it hasn't really helped with getting started on tasks, especially those perceived as boring. I even had to psych myself up to sit down and start meditating, even though I knew I would enjoy it.

I didn't know until a year or two ago that non-stimulant medication existed to treat ADHD. I always thought it was only Adderall and the like, and I couldn't risk anything that would ramp my anxiety up, or take additional treatment for the anxiety with SSRIs because I have severe hemophilia and any additional risk of bleeding from SSRIs was an untenable proposition.

After sitting on the idea for some time and just hoping that I could fix it with more meditation, I finally decided to see a psychiatrist. The doctor suggested Atomoxetine, but said it doesn't work for most people and even then takes 3-4 weeks to take full effect. I started on the absurdly low dose of 10mg/day for the first month to be sure it wouldn't cause additional bleeds. By day 3 I could see a huge improvement in my working memory and ability to perform tasks. It gave me insomnia for a bit but I would wake up at 3 AM, sit down happily to work and write the best code I've written in years. I could not believe the difference it made. There were quite a few side effects initially but I was willing to put up with them because of how smoothly my brain was functioning. I became a nicer person to deal with. I felt this sense of possibility and freedom that I haven't felt since my 20s. My only regret is not having done this sooner.

So yeah, please don't avoid medication based on internet reading.

Same for me with Adderall.

I do wonder if being highly functional and feeling capable is normal though, like as a species it seems almost dysfunctional to happily plow through 8 hour workdays and bills and appointments and all the little bureaucracies we have to navigate. Sometimes a little voice screams "Run to the woods!" when I sit down and look at a long todo list for the day, but with Adderall I can generate some semblance of enjoyment from ticking off the boxes.

Granted our world is what it is, and we are mostly helpless to enact large changes. Finding some kind of peace with reality is probably better than bashing your head against why you don't fit into it well.

As someone who tried citalopram escitalopram and sertraline, along with venlaflaxine and fluvoximine, I would suggest doing a pharmacological test for psychiatric medications.

I am an intermediate metabolized for the first three and the ones I was on most long. It did not suit me and made my orgasms go from ‘wtf’ to ‘that’s it?’ And they are still not normal 2 years after discontinuation.

I am still depressed and anxious to the point of serious consideration of these medicines to save myself, but you can save yourself the experimentation by doing a simple test and avoiding those medicines.

Anxiety depression panic attacks are something I wish more people studied along with sexual health.

Same for me with buproprion. Night and day difference. Made me wonder how different my life would be if I had been diagnosed appropriately when I was a kid.

Yah. Measuring the effects of these drugs with a single effect size number is ridiculous. They work exceptionally well for some people (myself included). It seems as well that SSRIs work much more reliably on anxiety disorders than on depression.

Getting on them can be a ball ache (or entirely painless; escitalopram was easy on and easy off, Wellbutrin was a nightmare to get on, but also easy off), but entirely worth a shot for anyone symptomatic.

Thank you for saying this, I wholeheartedly agree. Antidepressants have an excessively bad reputation.

I'm sure they have their problems too on occasion, but for me the decision to start taking Escitalopram was one of the best things I've ever done.

The side effects were totally negligible compared to the benefits.

I've stopped taking it a year ago or so and... it's basically cured me.

I'm not saying antidepressant are a literal pharmaceutical cure for depression, but in my case it simply put me in a position mentally to change habits and patterns of thinking in a sustainable way.

My only regret is not doing this 10 years earlier; the poor reputation contributed to that.

> I could cry with joy because I could finally understand emotionally why people like the Christmas season.

SSRIs are known to induce a

https://en.wikipedia.org/wiki/Mixed_affective_state

I seriously messed up my life early on by not being able to recognize the difference between being happy and manic.

One of those manic symptoms was often feeling like crying out of joy, and another was feeling way more cognitively capable that I was.

I’m glad to hear that. Another frame is that your depression turned out to be “math hard” rather than bodybuilding hard [0]. Your disciplined, methodical approaches were steady applications of effort, whereas what you actually needed was easy to implement but hard to envision.

[0] https://www.alexcrompton.com/blog/2017/05/26/hard-is-not-def...

Same story here, but different drugs. Every year Nov to Mar means no lapses whatsoever in diet, exercise, sleep, supplements, clutter, lighting otherwise the SAD will seep in and erode me. I tried udosing ADHD meds this year and suddenly subsistence is easy and I have gas left in the tank for worthwhile things.

I feel like I speedrun Maslow's hierarchy of needs.

No anhedonia so far this year and my creative output is at all-time high. Hope that helps someone get over their own biases about prescriptions.

I experienced this but ended up getting off of them after developing some back/hip issues but I didn’t think it was related, it wasn’t until I quit the citalopram that my shoulders were suddenly relaxed and the hip “looseness” or constant need to be adjusted back into place went away, like everything tightened back up, it is really strange, then I looked up how SSRIs can impact this and even bone healing, decided I couldn’t risk my body falling apart.

> This just goes to show that for me, they're extremely effective.

I am not so convinced. Perhaps your case was simpler, but people can feel chronic depression. They may take some drugs to modify that, but what if the external factors won't change? You can see this issue for some people who have a disease that only gets progressively worse. I think we can not unify all this as "dislike on antidepressants" as a one-size-fits-all formula.

They've been losing ground to placebo in more recent research.

Plus, most of the more serious side effects take a lot more time to manifest than the typical length any given patient remained in the older clinical trials that secured FDA approval and grounded the official manufacturer literature.

I am glad we have these tools, but I suspect they are vastly overused, and patients not well informed.

Tangent… but for sweaty feet, try a ski boot dryer!

You can get them for $50… they dry out my shoes which makes them last a lot longer before they get so smelly I have to throw them away. Plus, who doesn’t like warm shoes in the morning?

That, and there are some creams called Sweat Block or whatever you can rub on your feet which reduce sweating. Those work as well.

I described SSRIs like this:

When you're depressed, you're in a hole that's too deep to get out of.

The SSRI basically shovels stuff from the top of the hole to the bottom of the hole so your head is above ground level. You are still in the hole though and you need to climb out of it.

The things that keep me away from SSRIs are the potential for addiction and not being able to take psychedelics.

I had a friend on SSRIs not tell us they were on them when they hit a DMT vape pen at a party years ago and they got serotonin syndrome. Had I known I would have warned them not to.

I had severe SAD to the point of having a mental break where I told my wife I was flying that very day to Miami to get away from the cold. I didn’t end up flying to Miami, which is likely why I’m still married…

So I ended up spending $300 on LED bulbs, both corn bulbs and 200W equivalent, bought some 7-Way splitters for my ceiling fan so it’s holding 28 light bulbs (people have joked I have a “biblically accurate ceiling fan” because it’s so bizarre looking, like a weird glowing biblical angel), and get about 10,000 lux in my home office now. As a bonus, I don’t have to run a space heater in my home office (since I only need it in winter, I’d have been using that electricity anyway via a space heater). Solved the issue completely for me.

Have you tried SAD lamp light therapy? But not those lamps you get on amazon or other marketed SAD lamps, those are a scam. Just buy a 2 floodlights that are pretty powerful, say 100 watt each. Works like a charm. 15-30 mins a day its all it takes

Bessel van der Kolk also mentions in his excellent book "The Body keeps the Score" that the effect of antidepressants is correlated with the source of the depression. If the depression is a comorbidity from early childhood trauma then antidepressants are limited due to trauma-related reshaping of how the brain is organized. Cases like yours or those that a related to traumatic experiences as an adult are more the result of a shallow neurochemical imbalance which antidepressants are able to impact beneficially.

> Cold showers, ... no alcohol, strict sleeping rituals.

I feel like doing those three things would make me feel like reheated cat shit, regardless of the weather outside.

I still think you should have tried eating a banana first.

Imaging the number of people that this comment could inspire to get on SSRIs lol

I'm not saying it's a bad.

But I'm also saying there are no magic pills...!

> I won the SSRI lottery I guess, the side effect are sweaty feet, vivid dreams and a dry mouth. That's all.

Yes, you did. Had the same medication and got tremors and stiffness so bad I thought I had early-onset Parkinson. Could hardly unlock the door without dropping the keys five or six times. Fortunately, it ceased when I stopped the SSRI.

Same I am in outstanding physical health and my diet / exercise is excellent. Taking Lexipro has made a massive improvement on my emotional bandwidth. I take vitamin D / fish oil and bits of other supplements. At least for me no question this medication even at a 10mg dose has made a major positive impact.

and then the effects wear of. You just feel "normal" or the same as before. I used to take ssri meds too. It was nice in the beginning. Stopping was a nightmare, I needed to taper down foe like half a year..

Similar story for me, but with Bupropion (Wellbutrin). None of the SSRIs/SNRIs worked for me, spent years trying different medications, Wellburtin was finally the one that worked, and oh man what a difference.

I had pretty much the same reaction after two days of taking it.

Took a while longer to get the dose right so that my anxiety also mostly disappeared, but the difference in quality of life it made for me is hard to put into words.

I had a similar experience except instead of antidepressants it was when i started taking Adderall as an adult. A sense of peace and serenity in my mind that I had never felt before, it was almost overwhelming.

If it is SAD have you tried bright daylight balanced lighting?

What dosage of Citalopram? 40 mg/day?

(Roughly equivalent to Lexapro 15mg/day; Saffron 30 mg/day if Crocin+Safranal properly standardized)

How do you know it was the SSRI?

To cherry-pick a quote from a review of SSRI studies:

>the magnitude of symptom reduction was about 40% with antidepressants and about 30% with placebo.

That tells me that antidepressants have some effectiveness, but placebos work shockingly well. You can give someone a sugar pill with no medical properties whatsoever, and a good portion of people will recover, likely crediting the pill for their recovery.

Re "citalopram" and "SSRI lottery I guess"...in fact, citalopram is not a true SSRI and in fact no SSRI is only an SSRI as they also on, at increasing doses, many other neurotransmitters like norepinephprine and Muscarinic acetylcholine receptors.

However, citalopram specifically has a big effect on the histaminegma the sigma-1 receptor. I will focus on the sigma-1 receptor:

https://www.sciencedirect.com/science/article/pii/S134786131...

Never heard of it? Yeah, don't be ashamed, it is the biggest secret in depression. In fact they are finding that many "SSRIs" are sigma-1 agonists, even prozac.

https://www.frontiersin.org/files/Articles/1691987/fnins-19-...

It tunrs out that Sigma receptors modulate glutamatergic dysfunction in depression, and glutamate, being excitatory, well, you can. make your assumptions from there.

https://www.frontiersin.org/journals/neuroscience/articles/1...

It seems the main function of the Sigma-1 receptor is Calcium release. And calcium ion channels are one of the most studies ion channels in mood disorders. By increasing calcium release you increase neuronal activity, hence, the uplifted mood.

It is too bad that the sigma-1 receptor is just starting to be studied and there is limited evidence of how omega-3 and Vitamin D effect it. But I do know that Vitamin D has a huge effect on SLC6A4 (SERT).

https://www.nature.com/articles/s41598-020-79388-7

I have Schizoaffective Disorder Bipolar Type (disabled) and have been on no less than 14 types of meds. I knwo how they work better than my psychiatrists, which I why I no longer take them. I also know my genetics which gave me clues to what is happening in my body. Now I eat a mostly seafood diet and my needs for meds has mostly vanished. I am still an odd old fellow, but at least I am not ranting in the streets or trying to kill myself anymore.

Meds saved my life, but a diet high in Omega 3, D, and a bunch of other things has removed so much suffering from my life, more than any medication has.

(Also, if you want to get into the weeds of depression, you might wat to look at ATP and depression https://onlinelibrary.wiley.com/doi/full/10.1111/cns.14536)

Thank you for your comment. I think that can help many people.

The side effects are suicidal ideation and brain zaps

As someone that falls on the side of “depression is real and antidepressants can help” it is very clear that there are people in this thread that need to hold their tongues because they know not of what they speak. (Not you OP)

There are some forms of depression that you cannot think or act your way out of. If you haven’t experienced that, I promise that you do not understand what it is like. You cannot really understand unless you have experienced it. Your opinion on it is irrelevant, and frequently offensive.

The same is true for people that say that antidepressants are mostly placebo. They are not. When people say that antidepressants saved their life, they aren’t joking or exaggerating in the least.

Yes, I understand that other therapies are also effective, and that some people are non-responsive to some drugs.

Keep your pet theories to yourself if you are not a subject matter expert or someone who has experienced it first hand.

Edit: I understand that the placebo effect is still an effect. My point is that there are a lot of people being incredibly dismissive of real lived experiences and outcomes on a VERY serious issue.

Do you take the citalopram year round, then?

sweet feet seems so random, maybe some serotonin receptors down there? are they noticeably sweety?

I'm guessing you can afford spending $300 on light therapy glasses.

Disclaimer: I'm not a doctor, but saw 4 seasons of dr. House. Moreover, few hours of Huberman Lab on sleep and light and most importantly, this episode of Additude Mag Podcast on curing SAD and ADHD day-rhytm shifting with light glasses: https://www.youtube.com/watch?v=fu4mLgkNc6I

What happens in the seasonal affective disorder season is the sunlight pattern diverges from 6-18 that we evolved with. Without daily reminder of getting enough sun (or sun-like) light at the 6 o'clock⁰, your body clock will drift.

It can start by feeling groggy instead of refreshed in the morning, even if you've slept enough. And can escalate into loosing the will to do anything or even live.

No wonder. You're still an animal. You need to be fed, put to bed, etc. at a specific time. If you try to make your body sleep during the day, and eat and work during what body expects to be night, you won't really sleep and won't really live/work. Enough of not really sleeping and not really living - you mess up your body, your gut biome, your hormonal balance and your brain chemistry. You kind of should get depressed when you do it.

You can steer your body clock with light. Most of us do it, by exposing ourselves to strong (strong enough it won't matter if it includes blue wavelength or not).

But you can do it consciously (and in a way good for you) by putting on light therapy glasses (I'm using Lumiere 3¹, and they are not the only ones, find your own) at 6⁰ everyday, or right after you wake up if you're trying to readjust your rhythm. Or if you have time and want to save $200, use a stationary lamp and just sit in front of it doing nothing. I don't have the time. When readjusting, small doses of melatonin (0.5mg) 1h before sleep will accelerate body clock shift.

But don't listen to me, if you have SAD, you should really listen to that ADHD experts episode.

I feel for you, struggling with that stuff for a long time. Vit D, fish oil (lot of). All lights at home set to reduce intensity after 18. Strict going to bed routine. Still sleep poorly once in a while, but can do things in winter again. Hope it will help :)

0: choose whatever suits you. With small doses of melatonin and discipline in using light glasses you can even flip day and night. Just stay consistent, good farmer always feeds his cows at the same time.

1: at the time of buying ( fall '25 ) they were cheapest and best overall in norway. Solid build, ok battery, can have them on during yoga using attached rubbers and kind of can have them over glasses. Mine are very large and have blue light filter, but I manage 20min without eyeglasses. Medical certificate. Few leds, holo strip, battery and some plastic - my inner Scrooge says it's not worth $285, but everything else was worse and more expensive.

I also noticed that. Opened issue: https://github.com/ncase/blog/issues/4

That would be 5g. At this point everyone should notice that something is off. :-D 5000 mg of vitamin D3 = 200,000,000 IU (200 million IU)

If you don't have an underlying condition it is way better to get the Vitamin D from the sun in 10-30min increments per day after which you are saturated for the day. Overdose is not possible via the sun (excluding sun burns of course).

> A single, optimal sun exposure session might produce the equivalent of 10,000 to 25,000 IU from a supplement, but it will not keep increasing with more time in the sun. That's your max per session.

Isn't the oral intake pretty much negligible anyway? I remember getting a vitamin d supplement in a syringe (to be put on bread, from a physician) containing a very large dosis.

I'm not stating the dosage is wrong. Looks like it is anyway.

That’s a large enough error that it calls the rest of the writing into question, in my opinion.

Also, be careful taking 5000 IU/day of Vitamin D. I did this for a few months and it was enough to send my blood levels over the top of the range, even in winter.

Too much Vitamin D is not good for you. The supplement fans have gone too far in recommending too high of dosages. My doctor said she’s seeing a lot of people with excessively high Vitamin D levels now that it has become popular.

Even 5000IU a day is huge and will likely result in calcium buildup.

So 5000 IU is the recommended amount?

yes, once i saw that i stopped reading. if the author can't get that right i am not going to trust anything else they say.

Is "IU" another case of xkcd 927?

I used an LLM to summarize and it told me 5000 IU.

Only recently again I read in the newspaper, that most products are overdosed. There is a typical number that the vitamin D products usually show, and in the article it said, that only up to 800 IU is safe, and everything above is an overdose. There are many products out there with 2000 UI or maybe even more. Beware.

EDIT: Wow, the HN-local doctors at it again. Imagine getting downvoted for sharing information from newspaper article (and honestly labeling that info as such), that probably was written by someone consulting medical professionals. But hey HN will know better!

It's unbelievable crazy what the author suggests, even say "10,000 IU if you're feeling daring / have darker skin / live in less sunny climates.".

Just a simple look at the side effects of high dosages:

Safety and side effects

Taken in typical doses, vitamin D is thought to be mainly safe.

But taking too much vitamin D in the form of supplements can be harmful and even deadly. Taking more than 4,000 IU a day of vitamin D might cause:

    Upset stomach and vomiting.
    Weight loss and not wanting to eat.
    Muscle weakness.
    Not being able to think clearly or quickly.
    Heart rhythm issues.
    Kidney stones and kidney damage.

https://www.mayoclinic.org/drugs-supplements-vitamin-d/art-2...

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!

Based on your own citation, this is untrue. The citation you have linked is a meta analysis of 31 trials, many of which specify no medication use at recruitment.

You are however correct about population being important (which is a big reason meta analyses can be very useful).

All my nutrient numbers improved when I became vegan because nearly every one in the US/UK is deficient in VitD, Omegas and B12.

Fortunately today’s vegan communities are much more aware of this so I started taking these supplements right up front and all my blood markers improved dramatically since when I consumed meat/dairy.

It’s annoying to hear some push back against this when it’s as simple as taking relatively safe supplements (just make sure you talk to a doctor, and not a social media influencer, about how much you should take, and if you get a chance to regularly check your bloodwork don’t miss out).

> as part of a new gym plan

There's your answer

Omega 3 comes from algae, which might be okay for some vegans.

> Then as part of a new gym plan, started taking Omega 3+VitD daily, and I just felt a sense of calm and peace after a few weeks. The massive uptick in exercise probably also helped

I would bet that 95% of that improvement or more was due to the exercise.

Your anecdote is common: People start taking Vitamin D or fish oil as part of a bigger plan to have a healthier lifestyle and then they attribute success to the pills, not the lifestyle changes.

> I was a vegan for 10 years, and found out I had basically zero Omega 3 in my blood

I see your disclaimer, but just for more context, vegans can get Omega 3 without taking pills per se. Flax seeds are an excellent source. I often add a spoonful to a bowl of oatmeal or as a pancake topping along with fruit sauce and granola.

  Eating ground flax seeds gives you more benefits than whole seeds, as whole seeds remain undigested and pass through the system.

  Most people can’t chew flaxseeds effectively, so they grind them first or swallow them whole. (They are tiny.) Nutrition experts do recommend grinding them first to release the fiber and the beneficial fatty acids. Flaxseeds are helpful for constipation and may lower cholesterol as well.

  Ground flaxseed goes rancid easily, however, so it should be kept in the freezer until you are ready to use it. If you buy it ground, you wouldn’t have to use the blender or coffee grinder to break those seeds up before you have breakfast.

The problem with the "your life objectively sucks" option is when you end up too depressed to actually bother doing anything and just give up. That's another case where drugs can help.

You mean relatively sucks. Else every single human ancestor would have to be super depressed too given the standard of life in the past.

> You might be depressed because you life objectively sucks

The problem with this that to a bad situation different people react differently - some trying to do what they can to improve the situation or at least don't make it worse and some give up and let situation to slip and become worse and worse (becoming a self fulfilling prophesy). It's not a choose one makes I think (it's likely a biological predisposition) but the difference is still exists.

People prone to depression genuinely believe the main (only) reason for a depression that the life sucks and as a result they avoid medical help and don't do anything which could help them.

This stuff is complex. There are no magic potions or hacks that work for everyone. No amount of positive thinking can fix physiological issues that you have because of some underlying condition. But it's quite possible to create new issues as a side effect of being depressed, stressed, chronically exhausted, etc. So, working on those issues is probably smart.

And each of those things can be caused by physiological issues as well. You might feel stressed because you don't sleep well. You might sleep poorly because you suffer from e.g. sleep Apnea. Which in turn might be because of a mix of physiological and other reasons (diet, weight, alcohol abuse, etc.).

Or you might be working too hard, which makes you stressed and causes you to lose a lot of sleep. Different causes that have similar results. Including long term physiological results. Your brain can actually get damaged if you chronically abuse it or neglect it. Many "between the ears" type problems are actually physiological.

Root causing your issues enables you to deal with them properly instead of fighting the symptoms.

Anyway, I take vitamin D and a few other things. Getting yourself checked out regularly once you hit middle age is a good idea. There's a lot of stuff that is long term lethal that a checkup can detect early. And some of it is fixable. I have the usual cardio vascular challenges that many people struggle with because of a combination of genetics, age, and life style. And indeed a vitamin D deficit.

I was also recommended to consume more omega-3 as well. Eat salmon. Work some flax/chia seeds in your breakfast. I put flax seeds in my yogurt and use it as a thickener in sauces as well. You have to grind it to dust for it to get absorbed properly. Dirt cheap and it doesn't mess with flavor/texture too much. I keep a jar of ground flax seeds in my fridge. Takes 2 minutes to top it up every 1-2 weeks or so with some freshly ground seeds.

But I'm also aware that me being a stressed startup founder has health consequences that a few pills and suplements won't fix for me. I need to actively make sure I get my rest and sleep. I deal a lot better with stressful situations when I'm well rested. And I seem to be better at avoiding getting in to those as well. And I feel happier. Sometimes the best thing I can do for my company is having a proper weekend or going to bed early enough that I can get my 8 hours of sleep. You can survive on 4 hours (been there done that), for a while. But most people are not at their peak performance if they do that. And it's not good for you to work yourself to exhaustion all the time.

Most people's lives objectively suck. Most of them are not depressed.

Pinpointing problems in your life as the cause of your depression is a trap.

That's the sorta standard socially accepted way of thinking about this. but uh... to a lot of people it doesn't ring quite true.

For example: if your life objectively sucks, why aren't you doing anything about it? Some people whose lives suck fix their lives, and other people get depressed and do nothing; what's the difference? And: all of us know somebody who appears to have a good life and therefore their depression is presumably a chemical imbalance thing but if you're being honest the vibes in their life are a bit off, actually, like you can tell they're not really getting everything they need out of it, that they're clearly good at masking (for example people who are clearly not thriving in their relationships) .... in which case sure medication could help but you can't shake the feeling that facing the reality of their life would help a lot more.

However! Questioning this stuff becomes a bit of a moral minefield. "Believing" in the chemical imbalance theory is part of why it's medically helpful. If your life has sucked for years and you could find no way of fixing it and then SSRIs helped, then you basically need to believe that it really was a chemical imbalance, because believing that it might not be threatens to take away the thing that's making your life work. So much so that I would bet at this point there are already readers of this comment who are ready to angrily reply to my preceding paragraphs, because the model I just described threatens their existence. (If so, wait a sec and read the rest...)

On the flip side, for some people not believing in the chemical imbalance model for some particular case might be important. Maybe they want to feel responsible for their life being bad, so they will be motivated to do something about it, and being happy due to drugs would make them feel complacent and okay with years passing by at a shitty job or something. Or picture someone whose parent has gone their whole life unable to take them seriously as an adult, which as a result means the child and parent have a bad relationship, and then picture the parent complaining about depression and taking medication for it. This can be really infuriating: the child thinks about the parent, "your life sucks because of the tension created by not treating people around you with respect, and you're so incapable of recognizing this even when it's told to your face regularly that you're taking drugs to feel better despite not fixing the problem". Now ascribing depression to medical problems seems like avoidance, and having people write off your frustrations and say that you're just depressed and need to take a drug for it is frustrating.

Just saying: the two narratives really get tangled up. I don't really know what to do about it, but I do think that some harm is done by harping on the concept of a "chemical imbalance". A lot of the issue is avoided if you just think of the drugs as helpful but don't choose any model (with its moral implications) for what exactly it is they're helping with. Just treat them as a tool for making you feel better.

Also, I suspect that people who have an intuitive aversion to mental health drugs are probably way overindexing on that intuition. I definitely did this for a long time, as did some friends I knew growing up. Turns out whatever your issues you can sometimes just deal with them sooner than later if you accept that doctors might be onto something. (Actually I think the reason people get stuck avoiding medication for so long is precisely that they feel like they're not allowed to be skeptical of them... which makes them kinda plant their feet in the ground and refuse to be open to it. That's kinda why I'm typing this long comment, to tell anyone reading that it is a reasonable thing to feel. And now that you know that maybe try them anyway..?)

Agreed, anyone that already struggles with something like this should quit caffeine. My life is so much better off of it, but I struggle to stay off of it because I'm addicted to the 2hr productivity boost vs the all-day steadiness when you're not on caffeine. Things that improve for me were: No sense of urgency for every single thing. Significantly improved confidence. Word things better and speak better in general. No hard crash later in the day. All my scattered thoughts become cohesive. No more random heart palpitations.

All of these likely got better due to the overall effect of decreased anxiety and not making ADHD worse. I'm not myself when on caffeine. Nikola Tesla quit all caffeine/other stimulants for a reason.

> Not just switching to "decaf" (which isn't)

Going to argue here, this is wildly bad advice. Decaf practically has no caffeine, it has 2-7 mg from what I can tell which is less then chocolate. 2-7mg is like impossible to notice and might aswell be water with how little there is.

As someone from the Middle East, just thinking about not drinking coffee makes me lose my will to live. It’s like asking me to wear sunglasses on a cloudy night.

I love coffee so much, I'd prefer to deal with the anxiety, and I do suffer from it.

I did the same thing and experienced the same effect.

I'd add that my ability to sleep naturally was negatively affected as side effect of medication. I tried a various combos to induce sleep and found the best solution to just be... exercise.

No caffeine, exercise, sleep lead to a significantly reduced anxiety and more.

Downside with going completely off caffeine is you get so tired and unfocused and it lasts for ages.

I tried doing this for almost a full year, and while the improved sleep and generally improved mood was fantastic, and even toward the end it was so much harder to get any focused work done.

I am in the middle of trying this out. When I first stopped caffeine I had better sleep and very vivid dreams every night. I also feel better as I think coffee was making my stomach too acidic which was causing me other indigestion problems, not to mention that coffee was nuking my teeth as well with acid.

Im on week 3 of no coffee now, I will maybe give it a month or two more to make a judgement call if I want to continue with coffee or not.

It is unfortunate as I really enjoy coffee, but it causes some issues for me with anxiety and stomach problems.

> if you struggle with anxiety or have some sort of ADHD

Those are two different things. Cutting out caffeine can help with anxiety but not ADHD. It's the opposite for ADHD, stimulates help significantly.

Tea, especially green tea, doesn’t have the same caffeine bioavailability as coffee – otherwise people would abuse it just as much as coffee.

I’m quite sensitive to caffeine, yet I can drink green tea all day without noticing much effect, while even a light coffee or a caffeine pill is clearly noticeable. I can also drink tea before going to sleep without any problems.

I cut coffee for over 6 months, and one of the most significant thing it did for me is that, when I resumed, I noticed that caffeine actually helped me feel more awake and alert (while I didn't notice any effect when taking a lot of it before stopping cold-turkey)

Fascinating.

Can you describe what else you tried? Other supplements? Any other non-food/supplement techniques like journaling, breathing, etc.? Any therapy and other similar human interventions?

After all those - is it / was it still the case that cutting caffeine drove the best outcome?

How long would you say it takes to feel the effects after switching? I did this a couple of years ago and as far as I remember the only real effect was my energy levels were more stable.

I gave it maybe 2-3 months and decided it's not worth it.

Tempted to give it another shot!

Very true! I recently found out that i am extremely sensitive to caffeine, and one cup at 6 pm makes me unable to fall asleep at night until 4 am. Trying to cut off the caffeine entirely now.

I wish I could cut down on my caffeine intake to help my ADHD. Unfortunately, I already have basically zero caffeine intake (apart from diet coke sometimes)

Counterpoint, purposely adding caffeine in the form of different mushroom coffees has greatly improved my ADHD symptoms.

Never going to advocate against eating whole foods if they taste good! But beware, the ALA omega 3 fat in flax and plant sources is not the DHA and EPA omega 3 fats used by animal cells, and so it's not as potent as what's in fish.

The main problem with ALA is that to have the good effects attributed to omega-3s, it must be converted by a limited supply of enzymes into EPA and DHA. As a result, only a small fraction of it has omega-3's effects — 10%–15%, maybe less. The remaining 85%–90% gets burned up as energy or metabolized in other ways. So in terms of omega-3 "power," a tablespoon of flaxseed oil is worth about 700 milligrams (mg) of EPA and DHA. That's still more than the 300 mg of EPA and DHA in many 1-gram fish oil capsules, but far less than what the 7 grams listed on the label might imply.

https://www.health.harvard.edu/heart-health/why-not-flaxseed...

Also, beware of omega 6 fats. Seed oils (corn, soy, canola) used in commercial food products are incredibly omega 6 dominant in terms of polyunsaturated fat content. Consequently, the ratio of omega 3 to omega 6 fats we consume has plummeted as food production has industrialized. Omega 3 fats are precursors to generally anti-inflammatory signaling compounds, whereas omega 6 fats are precursors to pro-inflammatory signaling compounds. The bias in fat intake leads to more pro-inflammatory signaling in the body, and a lot of alt health types have alleged this is a major causative factor in the obesity epidemic.

This is important for depression, because chronic brain inflammation as a cause of depression was one of the going hypotheses at least a decade ago when I last looked into all of this. Upping omega 3 intake is an intervention that can address chronic inflammation, which is potentially why it improves some cases of depression.

Pretty much nobody in the west needs more omega 6s these days. I hear even farmed salmon eat primarily corn and soy based feeds these days, meaning their fat ratio is skewed much more heavily toward omega 6 than wild salmon and fish.

I'm not an expert, but I've done a bunch of reading on this previously, and also skimmed the article which also mentions some parts of this.

First, when taking omega 3 supplements, you generally care about increasing the ratio of omega 3 to omega 6. Hemp hearts have much more omega 6 than omega 3, so they're not very effective for improving the ratio.

Second, hemp hearts contain ALA, while what you generally want to improve is EPA and DHA (this is also covered in TFA). The body can convert ALA to EPA and DHA, but it's not efficient.

So all in all, if Omega 3 for the article's stated benefits is what you want, this is not the way. I recommend looking into eating more fish, or if you want a vegan route, algae-based supplements. [0] is a decent source from the NIH about foods and their Omega 3 content, split by ALA/EPA/DHA.

[0]: https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthPro...

Psychology can change neurochemistry but only in certain limited ways. Many people are on antidepressants long term because that's the only thing that works for them. Taking antidepressants is already stigmatized enough. People should just do what makes them feel best over the long run. Your rule of thumb does not trump hard-won personal experiences.

We don't really know how SSRIs work, but there's some evidence that it's through desensitizing serotonin receptors, not directly addressing the lack of serotonin. If so, "use it or lose it" doesn't apply; long-term adaptation is the point, and SOMETIMES does persist after quitting.

>A good rule of thumb in biology and particular any kind of hormone production and balance is "use it or lose it" - if you start regularly receiving something externally, internal production will scale back and atrophy in response, in many cases permanently.

There are ways to "hack it".

For example, ~6 months ago I started trt (testosterone replacement). It was the best decision health wise ever. I feel way better psychologically, first time in my life I managed to stick with cardio training for so long (before 3 months was the most). There are other benefits too.

So what about the "loose it" part? Well there is a hormone called HCG one can take a twice a week to trick one's balls into producing some natural testosterone. Its use prevents atrophy and infertility.

>A good rule of thumb in biology and particular any kind of hormone production and balance is "use it or lose it" -

Very basic and very often wrong rule, so take it with a grain of salt.

Insulin for example is the opposite. "lose it then use it" would be a general rule for type 2 diabetics where insulin resistance commonly due to weight gain is the primary problem. Losing the weight leads to better uptake and usage. For a type 1 "lose it then use it" you typically lose the ability to produce insulin to an an autoimmune disorder, then are stuck using insulin for the rest of your life.

The body itself typically attempts to main homeostasis, but at population scales this is something that is going to have a massive range of ways it shows up. Evolution, at grand scales, doesn't care if you survive as long as enough of your population survives and breeds. At the end of the day you might just be one of those people that was born broken and to work properly you need replacement parts/chemicals. A working medical system should be there to figure out which case is which.

> If the problem was brain chemistry, wouldn't it be with them from birth until treatment

Ha, of course it can be! Our brain chemistry is not stable through our life! Many children are born with epilepsy, but some people develop it later in life. epilepsy, like all neurological disorders are nature AND nurture, genes AND the environment.

Using your roller coaster analogy, there very well may be genes that control; how much fear someone experiences when riding a roller coaster. The problem society has is telling people that they all should be able to not have feear riding a roller coaster and if youa re too afraid to ride a roller coaster you should take xanax.

>humans evolved in Africa, connected to oceans and trees and tribal living

Human evolved to have no modern medicine, indoor heating or refrigerators.