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Comment by lordentropy | Hacker News Reader

Daily morning and afternoon exposure to bright light might actually be more important to reducing depression than direct vitamin D supplementation. Low vitamin D might just be an indicator that you are not getting enough sunlight. Sunlight also affects melatonin and serotonin levels, and synchronizes your Circadian rhythm. Not sure why that article doesn't talk about Seasonal affective disorder (SAD), and how bright light therapy is considered an effective treatment for it.

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Sunlight’s effects on body chemistry also have a damping effect on inflammation. It’s a funny thing.

Sunlight has an impact on many chemical processes in and on the body. One example: Our skin is coated with a bunch of chemicals. There’s a number of different acidic chemicals. These are known as the “acid mantle”: https://en.wikipedia.org/wiki/Acid_mantle

One of these substances is urocanic acid. The body manufactures it as the trans-isoform. UV light – as in sunlight – causes it to change into cis-urocanic acid. (Ultraviolet-induced isomerization.)

Cis-urocanic acid fits a certain serotonin receptor – type 5-HT2A. Cis-urocanic acid is a 5-HT2A agonist. That receptor is known to be profoundly immunomodulatory.

It’s super interesting! There are some recent papers on it like “ Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor” – https://pubmed.ncbi.nlm.nih.gov/17085585/

“Molecular basis for cis-urocanic acid as a 5-HT2A receptor agonist” – https://www.sciencedirect.com/science/article/pii/S0960894X0...

This is absolutely fascinating. I think people take me as a crackpot when I point to these papers. These are just simple and solid papers from molecular biology :)

You, sir, just blew my mind. I have some reading material to go through. This is fascinating indeed!!

I’m so glad to be able to share these papers with someone!

I have no formal higher-level education in biology btw. Just high-school level or so?

And I had no idea this was a thing – I just found one of these papers purely by accident.

I don’t even remember what I was digging for on Google Scholar. I think it was something related to psoriasis. (It runs in the family.)

I think I might have been trying to look for any hints on whether I was really seeing my psoriasis skin condition improve after starting to take ADHD medication. – And yes, I do believe that is the case, and that it’s related to serotonin.

I feel a little like this might be construed as oversharing – it’s a story about science and I don’t know how to tell it in another way :)

So I got a diagnosis of ADHD at age 39½. A carefully done and clinically sound diagnosis. Many things in my life now make a lot more sense than they did. Whatever ADHD actually is. I turn out to be somewhat of a poster child?, for “internal” ADHD. I respond very well to a small dose of lisdexamfetamine. (Vyvanse in the US. Elvanse over here.) When I started taking it, old friends would say things like”uh… What happened to you? You’re so… composed? serene?” “–Ah, yes. It is all the amphetamine I am taking.”

And I give them one to try? because it’s so mild? And this friend is a lot like me so it can’t be that crazy? And they spend 24 hours with a clenched jaw and can’t sleep for a whole night. Biochemistry is wild.

And after a few weeks I thought my skin condition was improving. It didn’t make any sense. Didn’t even occur to me that it could be the ADHD medication. But then I tried reading about the compound on wikipedia, what it does, what receptors it acts on. And then start looking for papers with kind of random keywords on Google Scholar? Because I didn’t know what I could be looking for or the words for it? And that’s how I found out about cis-urocanic acid. I think mostly because “cis-urocanic acid” seemed like an odd and funny name for a thing. And as I learned later, word-for-word, cis-urocanic acid does have a really odd and funny meaning. It means “this-side dog-pee acid”. “Uro-canic” because that’s where they found it for the first time. And “trans urocanic acid” means “the-other-side dog pee acid”.

And I’m at the computer just going “wh… what? Huh? Lol?”

And yes, as far as I understand it, the lisdexamfetamine does help my psoriasis, and because of some part of its influence on the serotonin balance in my body. Amphetamines are serotonin-releasing agents. I am fascinated by the papers on that part of it but it’s also clear that I can’t speak with any confidence. As I understand it, the ever-so-slight serotonin “venting” caused by amphetamine might do a few things that cause this effect: Slightly downregulates pro-inflammatory serotonin receptors, slightly activates anti-inflammatory serotonin receptors, and sliiiightly reduces the amount of serotonin in the average blood platelet’s payload. (“Wh… what? Huh??”)

And yeah, on the way there I finally learned why my skin is clearer and less inflamed in the summertime. And why the UV phototherapy for psoriasis works. And the medically prescribed trips to the suntanning clinic in the Canary Islands for the patients with really bad psoriasis? Yep, that’s a thing, and it works, and I don’t think they ever really knew why, and urocanic acid is probably a big part of the reason it does, and even if those papers are out, I bet that the dermatologists don’t know about them because there’s just so much science out there.

And we have no idea how easily accessible it is. My dermatologist probably doesn’t know about Google Scholar? And certainly not sci-hub. Or the amazing discussion between scientists one can find on Twitter.

Funny thing right!!

I'm glad you're getting to the bottom of your health issues. Sounds like you're on the right track.

I'm fascinated by it because of my history:

I've had acne my whole life. Starting at 11, I'm 39 now. Still have it. I've tried every medication known to man. Nothing works. Dermatologists can't explain it, they just give me the same canned answer "You produce too much sebum". "Ok, how can we control that?". "We're trying".

I take two showers a day to try to ward off the sebum oil from clogging my pores. I wash my face, hands, and all multiple times a day and wipe with clinical strength salicylic acid (6% instead of 3% you can get over the counter).

Still, nothing works. Except one thing which could have adverse affects on me later. The Sun.

When I get a tan, all my acne clears up for a brief while. Maybe that's the cis-urocanic acid doing it's thing. Maybe it's the sun burning that sebum and sealing the pore. I'm not sure. I'm pretty sure I'll get skin cancer if I continue this line of "treatment" but I'm out of options. It's ridiculous.

It's on my face, my arms, my back, my ass, my legs, my chest and has been since middle-school. I'm ready to just graft the whole body.

So thanks again as I have some other avenues to discuss with my doctors as well as some research to show them.

I assume you looked into Accutane treatment? It has worked wonders for multiple people I know.

I was on Claravis for 8 months with no improvement. Still looking for a remedy, even if just temporary.

I will say that initially Accutane worked. For the first few months it cleared up the acne on my face but after a few more months it came back with a vengeance.

> That receptor is known to be profoundly immunomodulatory

Any change for a layman's explanation on what that means? This seems super fascinating but admittedly above my understanding.

immunomodulatory (immuno-modulatory) = modulates (i.e. controls) the immune system

It’s actually quite reasonable and intuitive that an integral part of our environment i.e. the sun is beneficial or at least has modulatory effects on ourselves. It’s too much a reductionist approach to think sunlight -> bad because of it’s immediate associations with some types of skin cancers.

Anecdata: I grew up in LA. I was always relatively healthy. Moved to NYC. Developed autoimmune disease by my 6th year in NYC.

I often wonder if I would have developed the disease if I had stayed in LA.

I think changing location does have a huge effect. Personally when I go to LA or SF (from Texas) I get sick 100% of the time, without fail.

For some reason I was often sick when I lived in Stockholm (Sweden). A friend there mentioned having the same problem.

Stockholm Syndrome?

people in the past would grab a small jar full of dirt from home and drink it whenever countering some ailment, I actually think that'd still work due to the recent researches on gut bacterial and it's influences on immune system and all...

Who, where, and when? Not doubting just curious about the practice.

I never heard or read about this and I used to read about past practices a lot. Who, when and where? I mean, which social class, which place and period and how prevalent it was?

There is actually real science behind this idea of drinking your home dirt (I'm not sure if its apocryphal or anecdotal). The reason many people experience stomach upset or constipation while on vacation is because their gut micribiome is unaccustomed to the new environment.

And yet lots of dermatologists will tell you to avoid sunlight.

The medical community is full of contradictions.

Everything in moderation.

EDIT: Except lava.

At first I read "except Java"

Lowercase L looks like capital i in some fonts.

Clearly it's Iava, the Latin word for Java. Quidquid Iava quondam scribum, omni currum, sed delenda est.

sed delenda est? sed sed editor consuetus textorum est!

Still true

The floor might be lava.

Until recently not going out much wasn’t a big factor.

I’ve been feeling sicker than usual lately. Stupid amount of rain in NSW. Went out yesterday morning on a bright sunny day and suddenly I felt much better.

>> The medical community is full of contradictions.

We added iodine to salt to prevent deficiency, then decades later told everyone to avoid salt. I've found iodine to be a huge piece of the puzzle - certainly not a panacea but one of several go to solutions.

The American Heart Association recommends no more than 1500 milligrams of sodium per day.

Because sodium is being added to packaged and processed foods, the average American was getting way more sodium than the recommended amount. And given the number of obese people and those with hypertension who are salt-sensitive, lots of people were getting way more sodium than was healthy for them.

There's also ample evidence that 1500mg is too low. https://www.webmd.com/food-recipes/news/20140402/cdc-salt-gu....

Unlike white sugar which seems to be bad for humans in nearly any amount, salt is an essential nutrient. I suspect it was so demonized as an attempt to deflect blame off of other food additives such as sugar. Low sodium diets may make sense for people with high blood pressure, but it isn't something that everybody should be doing.

It seems grossly irresponsible to only highlight the dangers of high sodium while ignoring the dangers of low sodium diets.

It's not the total amount of sodium but the concentration of the dose of sodium which will affect your blood pressure.

see https://www.youtube.com/watch?v=LbSic4Oo8ME&t=420s

So if your food tastes salty, you should drink more water to dilute the concentration (and hopefully you won't drink so much water to induce hyponatremia - it's a balancing act).

Later in the above-mentioned YouTube video, the doctor mentions that drinking water before you get that thirsty feeling is better for you.

By the time you get the thirsty feeling, your body has switched over to converting glucose to fructose, etc.

I recently listened to a great podcast [1] on the importance of salt and its role in proper brain functioning—the host is a tenured professor of Neurobiology and Ophthalmology at Stanford.

Part of the into: Additionally, I examine research findings suggesting that some individuals might benefit from increased intake of sodium and other electrolytes (magnesium and potassium) to enhance mental performance, lessen anxiety, and offset dizziness. Yet, other people may need less sodium. I discuss how you can determine your optimal sodium intake and why sodium intake levels need to be uniquely tailored to an individual’s lifestyle.

[1]: https://hubermanlab.com/using-salt-to-optimize-mental-and-ph...

I'm a little shocked at only 2 mentions so far of Huberman on this topic. As you know he goes into great detail here, and a panoply of related health issues.

I don't feel like I tried to do a low salt diet, but I don't eat pre packaged foods and normally cut out skipped salt just because it had such a bad rap.

Recently I started drinking a homemade electrolyte and if I miss it for a few days I can really tell. Increasing my salt and potassium has made my head feel better, I don't get dizzy standing up quickly, I got rid of the always thirsty feeling and my circulation is better (fingers aren't cold all the time).

Why did I make this change? My wife had a bunch of tests. The heart doctor said everything was great and to increase salt in the diet. We eat the same and many of the things I listed were mentioned in her appointment - so I figured it would likely be good for me.

Pass the salt.

Is salt added to processed foods iodated?

Of course not

Usually and in most places, probably not [1].

Some processed food manufacturers have started using iodized salt in some of their products in recent years at least where I live, though. (Northern Europe)

I don't know if that's an entirely a local thing or a wider thing e.g. in the EU. AFAIK the local soil here isn't that rich in iodine and so produce doesn't end up containing as much iodine either. The local food authority ended up recommending that iodized salt be used not only in schools etc. but also in bakeries and the food industry. Apparently some have followed suit, although not to a full extent.

A quick look at some store-bought packaged bread and the package of a frozen baguette I ate last night shows a bit more than half of them have or had iodized salt. That includes, perhaps a little surprisingly, the store-brand frozen baguette. The few other packages I have at hand don't indicate iodized salt but I've heard its use in the food industry has increased from the practically zero it used to be.

So, the answer might be a resounding no or a less resounding one, depending on where you are.

[1] Source: general impression of what I've read and heard, so basically a hunch

Well, the basis for the AHA recommendation is probably bogus. So there's that issue as well.

I … have never in my life heard of salt contributing to obesity. I’ve struggled with being severely overweight. I’m medically monitored for hypertension, both because of my weight history and medication which should increase my blood pressure. I struggle now to keep weight on. Salt is not a factor.

Salt was said to contribute to high blood pressure, not obesity. Congrats on taking control of your health!

> I struggle now to keep weight on.

What was the change you made?

At around 1h16m, Dr. Rick Johnson talks about how the human body on a high salt diet can convert glucose to fructose.

https://www.youtube.com/watch?v=LbSic4Oo8ME&t=4590s

If you're eating a high glucose/carb diet, the body will convert glucose to fructose. Enough fructose will switch your body from fat-burning to fat-storage mode => obesity.

Hypertension (high blood pressure) can be caused by high uric acid levels.

Foods high in fructose and purines (beer, anchovies) will increase uric acid.

I sound like a spokesperson for this video, but watch the video for how fructose (and high purine content food - beer, anchovies et al.) causes high uric acid -> high blood pressure and gout: https://www.youtube.com/watch?v=LbSic4Oo8ME

But most of that salt does not have iodine added.

Cranberries are how I get iodine into my diet. Not-from-concentrate Cranberry juice from TJs, primarily.

Didn't know cranberries contained it. How much every day do you drink ?

Not a lot, 3-4 oz. covers all of your daily iodine needs and then some. I have it with my breakfast because having it later in the day can affect your sleep quality. I learned about this from listening to Stan Efferding talk about his "Vertical Diet."

> The medical community is full of contradictions.

Looking after our physical and mental health via modulation of multitudes of interrelated bodily systems and their unique chemistry and biology is a massive multivariate optimisation problem.

However, there are reasonable heuristics we can use as a guide for better outcomes, for example, "spend more time in nature" - it's probably no coincidence that doing so is reasonably good for us given we've effectively evolved over many millenia to make the most of "being in nature".

Human biology is made up a number of interacting systems, negative and positive feedback loops and other biochemical pathways.

If you focus on individual mechanisms, it looks like contradictions, but as a whole it makes sense.

Sunlight is beneficial for vitamin D production, but harmful when it comes to UV damage.

Both can be true and not contradictory.

And in terms of evolution it makes sense. A lack of vitamin d early in life could effect reproductive success. Skin cancer in your fifties not so much. There just isn't selective pressure.

Another factor to layer on as well!

As humans developed, evolution didn't have to create the optimal system, just a system that gets the organism to reproductive years. After that? Irrelevant.

That could point to the challenge of fixing diseases of aging. A good analogy is programming - if the program you came up with uses 8 bit variables, and that limitation causes problems later, well, you're going to have to start from scratch to fix it.

I think that's about excessive sunbathing, which is a thing in certain circles, and certainly was a few decades ago. These days everybody is sitting inside with their games and streaming services, and I think it would do a lot of people a lot of good to go outside a bit more often. Just don't spend it at the baking in the sun all day long at the beach.

Sunlight exposure also stimulates nitric oxide production, which is important for circulatory system health.

Ah!! This is interesting. Many thanks!

Sometimes I order random supplements on a whim. I don’t remember why I ordered arginine.

It turns out that it very clearly and obviously helps my fiancee’s type 1 diabetes blood sugar control – like, a lot! We have a blood glucose meter and you can kind of just see it on the graph. Takes a while but the blood sugar just kind of obeys control a bit better if she takes arginine.

And it turns out there are a bunch of papers out on that too. I had no idea.

‘Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of the first interim analysis’ – https://scholar.google.com/scholar?q=arginine%20diabetes&btn...

And it turns out that arginine supplementation seems to help in hospitalized COVID-19 patients. For reasons which make sense – including nitric oxide production and cardiovascular function.

https://pubmed.ncbi.nlm.nih.gov/34522871/

Sunlight having an effect on nitric oxide production could be very important and useful for us to know! To help us manage her blood sugar and that whole biological picture. Thank you very much!

Oops!, please note: I pasted the title of the paper behind the second link… up there by the first link which is a Google Scholar search for “arginine diabetes”. And it’s too late to edit. Apologies!

Thank you for this fascinating comment! I can't wait to read through all of your links.

Latitude matters though. The farther north you are the more time in the sun you’d need. In some far north places, the sun you do get is not strong enough to get any Vit D.

http://web.archive.org/web/20210302053343/https://jaoa.org/a...

https://www.grassrootshealth.net/document/sunshine-calendar/

Indeed, the UK which is further north than the majority of Canada's population has effective vitamin D from the Sun only from March to September. Spring Equinox to autumn equinox basically. The sun is too low even though it might be much warmer than lower latitudes!

Yurp. I live in the south of England and even here I take vit D for pretty much that time period or I end up with little to no energy. I always make sure to go outside as much as I can, but when the sun is coming up at 8am and has gone down by 6pm it's pretty hard to get enough daylight and also work.

Worse in Edinburgh. Sunset is at 4pm for god's sake.

Greetings from Reykjavík Iceland

In the Southern Hemisphere (yes, people do live south of the equator) this advice is complicated by the ozone hole causing the risk of skin cancer to be much higher than in the northern hemisphere.

Anecdotally agree with this. I have vitamin D deficiency, was given 50,000 IU a week vitamin D to get it up. Never worked.

Went to the beach one week and got blood tested again and my vitamin D levels climbed significantly. Now I make it a point to get outside and sunlight

A lot of modern "problems" can be solved this way. The term koyaanisqatsi comes to mind, life out of balance.

Had super low Vit D. Was stuck in bed for a year. A few months of Vit D and a few other diet and supplements changes and I was out kayaking every weekend.

My experience anyway

What dose and diet changes did you do?

3,000u daily. Switched to AIP diet.

Six months earlier had started. Started magnesium, b12, fish oil, Vit E.

Now I take a 5000u/k2 combo.

Now on LDN in addition That seems to be the final major piece to fully normal life.

AIP diet: autoimmune protocol diet.

https://www.healthline.com/nutrition/aip-diet-autoimmune-pro...

The heaviest man in Mexico was bedridden for years. He was depressed, but besides being humongous, and trapped in a bed; one of his biggest complains was muscle aches.

A doctor gave him vitamin D supplements and he said the pain went away.

It made a bit of sence to me, but the amount of food this guy consumed daily was staggering. I just wouldn't think a person would be deficient in D with the amount of animal products this man consumed. I just assumed even though he never saw the light of day for 15 years.

My point is it just suprised me.

Antidotially, I have been depressed (dysthymia--low level) for a good 30 years, and found sunlight didn't help me. I don't eat a lot, but i'm not a vegetarian either.

I actually feel better during the winter. I do have allergies though.

According to my doctor, all he ever said about depression is "All my patients are different. Oh, my fee will be $----. Your depression is situational.". I know he is partially right. (He doesn't overcharge me compared to the horror stories I have heard here. I just believe most psychotropic drugs should not require more one office visit, especially if you are on a low dose, and not abusing them.)

> was given 50,000 IU a week vitamin D to get it up.

It should have gone up significantly. I wonder if your body has a problem with Vit D absorption. I was put on the same dose of vit d for a treatment and I felt it within 20 minutes.

Is vitamin D fat soluble? If so, pretty sure it needs to be consumed with fat. That's partly why it's common in milk.

It is fat soluble, but it doesn't need to be consumed with fat. It's believed that that will help improve uptake, though. (I don't, I take it in the mornings long before my first meal and that seems to be effective for me based on my test results.)

https://www.jandonline.org/article/S2212-2672%2814%2901468-3...

"The mean peak (12-hour) plasma vitamin D-3 level after the dose was 32% (95% CI 11% to 52%) greater in subjects consuming fat-containing compared with fat-free meals (P=0.003)."

It's common in milk because it helps with calcium absorption.

This is correct:

https://www.bones.nih.gov/health-info/bone/bone-health/nutri....

Takes months to rise your vitamin D levels.

This. It is amazing how long blood pressure pills, cholesterol pills, and vitamins take to make a budge in your blood tests.

>Went to the beach one week and got blood tested again and my vitamin D levels climbed significantly.

Well, I think I just justified my beach vacation. Thanks!

The point was that sunlight does more than raise vitamin D, not that it's better than supplementation at raising vitamin D.

In rare cases, hypovitaminosis D can be a symptom of heavy metal toxicity. If someone is getting adequate vitamin D intake but levels are still low then it can be worth testing for metals levels.

https://www.tandfonline.com/doi/abs/10.1080/07315724.1994.10...

Good example of correlation and not causation.

I think you are definitely onto something here. I used to take 10k IU vitamin D a day and still felt meh, but getting a bright ass white light (2300 lumens) in my room has uplifted my mood, increased wakefulness, and boosted my general productivity alot. I used to have a warm Phillips Hue and I couldn't do any work in my room without wanting to nap.

> Daily morning and afternoon exposure to bright light might actually be more important to reducing depression than direct vitamin D supplementation.

I don't understand how this is even a question. It's like people have no idea what's doing them good. Sure, I understand that scientific evidence is helpful, but this isn't particularly rocket science?

The difference between being in the sun and taking vitaminD is perceivable. Taking vitaminD doesn't make one feel better even to a fraction of how one feels after hours in the sun.

If I owned a health insurance company I'd be subsiding rents for people to move to apartments with better sunlight. It would very directly save money.

I'd also cut premiums and copays for people who exercise regularly and track it.

Maybe even give free national park passes and gym memberships to patients.

All this stuff costs pennies compared to the cost of the various treatments that people are needing these days.

Sunlight direct on the retina either without any obstructions or only through eyelids loads an enzyme necessary for serotonin production. The required amount of sunlight on the retina to reduce depression is 3 or more 20-30 minute sessions. It is actually harder than it might seem to get that much every week.

Had a consult with a sleep doctor, he stressed the importance of getting out for morning light for at least 30 minutes with no sunglasses.

Why no sunglasses?

Morning light hitting your eyes has a significant psychological impact. Sunglasses cut way down on that. It’s discussed in one of Huberman’s sleep related podcast episodes if you’re interested

I am thinking the same, and in a midst of self experiment where I ensure I get a decent dose of just seeing the world in bright daylight. Week into it and my sleep feels pretty solid. Easy to avoid daylight when working indoors all day.

Came here to say this:

VD may be it, or even indirectly a measure of 'not getting outside' enough.

Even the sunlight may not be it, literally a walk in the woods might be providing the effect.

Or rather 'spending too much time in our own minds' etc..

Bright, direct light seems to be a major component, which is not what most people think of being in the "woods." See:

https://news.ycombinator.com/item?id=31306477

Would wearing glasses, specially blue light blocking glasses make sun's effect on your circadian rhythm less pronounced?

That's interesting. I have Myopia and I permanantly put glasses with Bkue light blocking. I always had trouble with my circadian rythm and very often I find it extremely hard to have a fixed sleeping schedule, let alone sleeping early. I wonder if that has smthng to do with it. I also live in a northern country where the sun is a very rare event, especially during the winter.

I just went over 8 years without seeing the sun (jail). I wonder what the long term effects are?

Probably not good, and just one of the reasons why incarceration should be an absolute last resort.

Welcome out!

And when incarceration does happen, it should be in a humane prison where inmates get to go outside and do some normal activity. In too many parts of the world, prisons seem to be designed to be utter hellholes meant to destroy people.

Gahdam, they never put you on the yard?

First 5 years was in a facility with no windows or access to the outside. Last 3 had windows that were too dirty to see out of but some feeling of sunlight came in. That facility had outside, but was allowed out probably 5 hours in total. I burned instantly after all that time without sunlight!

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