Breakdown products of niacin may spur vascular inflammation | Hacker News Reader

Breakdown products of niacin may spur vascular inflammation

arstechnica.com

65 pointsScubabear6828 comments

The researchers next turned to genomic analysis to see if any genetic changes could help explain these elevated levels. The genome-wide association study, involving data from nearly 50,000 people, linked elevated 2PY and 4PY levels to a gene that codes for an enzyme called ACMSD (aminocarboxymuconate semialdehyde decarboxylase).

The study has limitations. For one, the researchers don't have any information on the dietary niacin intake of the people in their cohorts.

Can someone explain to me why this is being described as "niacin is a problem" and not "We may have identified an obscure genetic disorder"? Because I'm failing to comprehend this.

They validated the link between 2PY and 4PY levels and inflammation in large-ish cohorts (US and EU) that were not screened for the genetic defect. They also found inflammation from 4PY in some in vitro studies as well as in vivo mouse studies. The genetic defect is what lead them down this line of inquiry, but it's not the only evidence of an issue with high levels of niacin metabolites. From what I understand, anyway.

Interesting that a lot of these things seem to be that both too much and too little being bad. Tricky to hit the sweet spot but it seems the best way is usually try and do it with diet.

I've seen a few times where they've noticed that, say, higher antioxidant intake is correlated with good health outcomes, so they set up a trial to give people a mega-dose to try and fight cancer or something and find it actually makes things worse. Seems for a lot of these nutrients and vitamins the benefit is an upside-down U-shape and supplementation can put you way past the peak benefit and into where it becomes harmful again...

Which is why multivitamins seems to be a bit of a scam and studies can't find any benefit from them. It's probably worth getting some bloods done and only take what you're deficient in - for example vitamin D being a common one.

Antioxidants are good in people and animals with a diet poor in vegetable and fruits. That's why all those studies show wondeful effects in rats that never translated to humans.

> Which is why multivitamins seems to be a bit of a scam and studies can't find any benefit from them.

As someone who has had scurvy before, I can guarantee you some people can find a benefit from them. Of course if you expect them to make you "healthier" (as if this is a one-dimensional property, which is problematic to begin with) regardless of your health to begin with you may find yourself unhappy with the results.

I suspect OP actually meant multivitamins. They come in such small doses that they likely don't achieve anything. I'm taking a few vitamins for specific results and thought "maybe I can just replace them with one of those prepared mixes?" Yeah, no. They contain 5-40x less than a single dedicated pill.

Also, they're advertised as a generic "feel better" thing, while most people won't be deficient in 90% of what those pills include. So what's the point them?

> Also, they're advertised as a generic "feel better" thing, while most people won't be deficient in 90% of what those pills include. So what's the point them?

That seems like more of a problem with advertising than the actual multivitamin.

> So what's the point them?

Presumably to overcome nutritional deficiencies!

How did you get scurvy?

Lack of vitamin C. I'm surprised this isn't better known: https://en.wikipedia.org/wiki/Scurvy

Yes I know lol, I'm asking how you had such low vitamin C intake with a modern diet.

> Seems for a lot of these nutrients and vitamins the benefit is an upside-down U-shape

This is true for almost anything, not just in medicine but also in engineering and in life in general. If you are seeing a variable where the benefits increase as the variable increases you are probably just not sampling the range where it plateus or the range where further increase of the variable becomes detrimental.

Almost as if the saying “everything in moderation” has empirical basis.

Yup. One engineer friend/mentor often had cause to criticize the "some is good, [so] more is better" approach to anything; he pretty much considered anyone doing that to be idiots.

And he's right — adding more of anything without thinking and measuring will almost always make things worse at some point.

You can go meta and apply that to thinking and measuring itself.

Yup, I think (ahem) the term for that is "analysis paralysis"

yes that's what I had in mind for thinking. for measuring it's all the different ways we've seen the last decades from those who claim to do data-driven decision making go astray.

Damn... and a lot of people are taking niacin/nicotinamide/etc. as supplements, some of which are supposed to help with longevity...

And all the people and their energy drinks

No studies have ever shown those substances to increase longevity in humans (or any higher primate species).

On the advice of my Dr 15 years ago I started taking 3 grams of niacin a day. Within 6 months my hdl more than doubled from the upper 20s to low 60s and my triglycerides dropped from > 600 to < 150 and have stayed that way since.

What's interesting/odd to me is that niacinamide is a common ingredient in skincare products designed to reduce redness and inflammation. Something something "the dose makes the poison"?

I wonder if that will change the offered tests. I'm not sure how common that is globally, but in my area you can't really get B3 tested in the usual places. There a few indirect things you can check in urine, but it's also not common.

This is likely already a well-known side-effect to anyone who has tried to pass a drug test. Niacin comes in a few forms, most of which will makes you heat up and turn red and possibly itchy.

Only niacin causes flushed reactions. The other forms simply don't

it's amazing how they're blaming niacin now... in my mind, the key word here is "processed food" and "cereals" right at the start of the article... and then the picture is of a woman in the meat section. Smells funny this whole thing.

"...known risk factors for those events, such as high cholesterol..." - see https://cholesterolcode.com/ - cholesterol might not do what ppl think it does.

A through eh.. breakdown of the study:

Massive New Study shows Niacin and NAD+ cause Heart Disease?? Is this true?

https://www.youtube.com/watch?v=xInw3F2AVTg

tldr:

1. malnutrition (like just eating maize corn that contains only few niacin) causes pellagra.

2. therefore, wheat and other cereals became fortified with niacin (aka Vitamin B3).

3. average niacin intake in the US is now at tolerable upper limit.

4. those excess amounts of niacin may be exacerbating cardiovascular disease: https://www.nature.com/articles/s41591-023-02793-8

Does the study say what too much is?

(I saw the full paper / report at one time and it was too much to take in)

I want to take 100-175mg a day without worrying, but now I have no idea.

The limit is based on blood levels, not intake. You can (and probably should) get your levels tested before deciding to supplement. They will probably tell you where you fall compared to the upper safe limit in the test result, or if not you should be able to find that number easily with an internet search.

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