"High levels of niacin linked to heart disease, new research suggests"

[JackBruce2024]

"High levels of niacin, an essential B vitamin, may raise the risk of heart disease by triggering inflammation and damaging blood vessels, according to new research. The report, published Monday in Nature Medicine, revealed a previously unknown risk from excessive amounts of the vitamin ..."

yahoo.com/news/high-levels-...

[pdpatient]

Thank you for the information. For the benefit of others, Niacin is Vitamin B3.

newsroom.clevelandclinic.or...

[Gioc]

This is nothing new, I'm sorry to say it, but once again ,in my opinion , they are confusing the various forms of vitamin b3.

The metabolites they refer to are those of NAM OR NICOTINAMIDE, a form of vitamin B3 different from Nicotinic acid vitamin B3NA NIACIN , which is also the one (NAM) used for supplementation in bread (not in Italy) because it is more stable.

Here is research that studies NAM and its effects on healthy people.

Title:” N-methyl-2-pyridone-5-carboxamide (2PY)-Major Metabolite of Nicotinamide: An Update on an Old Uremic Toxin“

ncbi.nlm.nih.gov/pmc/articl....

scienceofparkinsons.com/201...

Ultimately I no longer believe they are in good faith.

[park_bear in reply to Gioc]

Review Possible Adverse Effects of High-Dose Nicotinamide: Mechanisms and Safety Assessment

This recent review found many more beneficial effects than adverse effects. Adverse effects tended to show up at higher doses.

mdpi.com/2218-273X/10/5/687

[Gioc in reply to park_bear]

ty PB,

Here you could read original research:

nature.com/articles/s41591-...

Bah!🤷🏻‍♂️

[park_bear in reply to Gioc]

Good find!

[JackBruce2024 in reply to park_bear]

Thanks, PB

[JackBruce2024 in reply to Gioc]

Thanks Gioc!

[4everhealthy in reply to Gioc]

Big Pharma Sponsored the "study"...not scientists, in my opinion.

[MarionP in reply to 4everhealthy]

Very interesting is the comment section which follows the article in the Yahoo article... A couple of things:

1. The possibility that big pharma (called "Big Harma" by the particular commenter) suggests cases in which the FDA had put people in jail for suggesting that cholesterol was the body's response to repair damage to the inside vessel wall, (excepting low density and very low density LDL, which look like little daggers under the microscope and which a cardiologist once told me dig up like little shovels bits of the inner surface of the blood vessel such that the body would issue cholesterol in order to smooth over the ruptured surfaces to limit the inflammation... The idea of being that statins helps smooth back over that surface and therefore continued damage would help big pharma, who already had known for decades that such damage could be cured, rather than endlessly treated, by reducing or eliminating sugar, which mechanically clumps together in plasma solution and causes additional scratching just like LDL and VLDL to the vessel's surface... One of them even mentioned, sounding like a physician or a biochemist, that just about anybody with cardiovascular damage and related heart disease is either diabetic or pre-diabetic).

2. IN PASSING CONVERSATION, HARMFUL BIOLOGICAL SUCH AS CANCER CELLS CANNOT SURVIVE IN A ALKALINE ENVIRONMENT SO HEALTH PRACTITIONERS SUGGEST ADDING A PINCH, SOME SMALL AMOUNT THAT IS, OF BAKING SODA TO ONE'S DRINKING WATER... Has anybody heard of this???

I plan to run these questions by my cardiologist next visit but that is about 7 months out.

[Bolt_Upright]

Thanks Jack. I appreciate you sharing this. We all need to share information like this so we can re-evaluate our protocols.

For me, I did not find that article particularly convincing. Not yet at least.

I have a bias: I take 2 grams of Nicotinic Acid a day. That may be too much. Do your own research.

I'm not a scientist, but I had some issues with what the article said:

So they did 3 studies of groups of people, totaling about 4,300 people, and all of them either had heart disease or were suspected of having heart disease. So they did not compare these groups to people with no heart disease?

Then they say the presence of 4PY, predicted participants’ future risk of heart attack, stroke and death. I'd like to know the details of how accurately this prediction is. Since we don't have the paper itself we don't know what the increase in risk is supposed to be or how they calculated it.

Then they injected 4PY into mice. "When the rodents were injected with 4PY, inflammation increased in their blood vessels". Is this surprising? I don't know what 4PY is really, but I can't imagine it having a soothing effect on the mice. And we are not mice.

Here is a link to the study itself (well, the abstract):

A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk 2024 nature.com/articles/s41591-...

Here is a better written article on the same paper:

Study suggests high levels of vitamin B3 breakdown products are linked to higher risk of mortality, heart attacks, and stroke 2024 news-medical.net/news/20240...

"In the US and European validation cohorts, serological 2PY and 4PY levels showed associations with increased three-year major-type adverse cardiovascular event risk [adjusted hazard ratios (HRs) for 2PY of 1.6 and 2.0, respectively; and for the 4PY metabolite: 1.9 and 2.0, respectively). Elevated 4PY levels were still strongly related to the incidence of major-type adverse cardiovascular event risk in both persons with relatively maintained and compromised renal function."

So the way I read this, is the high levels of 2PY and 4PY basically double your 3 year chances of a cardiovascular event.

Poking around it looks like 4% would be a fair average 3 year CVD risk. So the Niacin would double that to 8%?

But I still can't get past the fact that everybody in the study either had, or was suspected of having CVD when they joined the study.

[Bolt_Upright in reply to Bolt_Upright]

I like this reddit comment on the paper (it says it the same as Gioc : reddit.com/r/Scholar/commen...

" More BS from Big Pharma trying to discredit niacin for the treatment of high cholesterol.

All the article really says is what has been known all along - it's best to take the immediate release form of niacin and stay away from the long-acting versions because the long acting versions of niacin are primarily metabolized through the hepatotoxic nicotinamide pathway, whereas the immediate release form of niacin is metabolized through the conjugation pathway that produces the prostaglandin mediated flushing reaction.

The boogie man 2PY and 4PY metabolites that this article focuses on are primarily the result of the nicotinamide pathway, and result from taking nicotinamide or one of the long acting versions. Yes, the metabolites of the nicotinamide pathway have LONG BEEN KNOWN to be NO GOOD, causing hepatotoxicity. And now, woo, woo, we find out that two of these metabolites, 2PY and 4PY, increase cardiovascular risk.

So, yeah, once again this Big Pharma supported POS propaganda tries to smear niacin by .... lumping it together with its long acting versions - nicotinamide and inositol hexanicotinate, which had long been know to be Bad For You.

Just to show you how bad this article is, and how deliberate its intent to smear niacin's well documented efficacy in lowering cholesterol,

It never differentiates between the two separate metabolic pathways for immediate release niacin versus long acting versions of nicotinamide. Look up this 2004 article from the Arch Int Med "New Perspectives on the Use of Niacin in the Treatment of Lipid Disorders" to learn more.

It never mentions that the 2PY and 4PY metabolites that it focuses on are the result of the nicotinamide pathway, not the conjugation pathway which metabolized niacin

Moral of the story - nothing to see here, move along folks, niacin works and is fine. Don't take nicotinamide or other long acting versions. THEY ARE NOT THE SAME THING. "

[Gioc in reply to Bolt_Upright]

Exactly!!!

[park_bear in reply to Bolt_Upright]

I'm not trying to start a fight here - just interested in getting down to the bottom of this.

In this study of niacin supplementation in humans, it appears that a substantial fraction of the niacin gets converted into 2PY:

Effect of the Rate of Niacin Administration on the Plasma and Urine Pharmacokinetics of Niacin and Its Metabolites

accp1.onlinelibrary.wiley.c...

"The metabolic profile of niacin is influenced by the rate of niacin administration. This study characterizes the effect of administration rate on the pharmacokinetics of niacin and its metabolites. Twelve healthy males were enrolled in an open-label, dose-rate escalation study and received 2000 mg niacin at 3 different dosing rates. Plasma was analyzed for niacin, nicotinuric acid, nicotinamide, and nicotinamide-N-oxide. Urine was analyzed for niacin and the metabolites nicotinuric acid, nicotinamide, nicotinamide-N-oxide, N-methylnicotinamide, and N-methyl-2-pyridone-5-carboxamide [2PY] "

It appears that there is less conversion with the fast release than with the slow release, but even with the fast release, 30% is converted to 2PY.

The full text including the table is behind a paywall.

Niacin metabolites

[Bolt_Upright in reply to park_bear]

Here is the full paper: Effect of the Rate of Niacin Administration on the Plasma and Urine Pharmacokinetics of Niacin and Its Metabolites 2013 sci-hub.ru/10.1177/00912700...

[Bolt_Upright in reply to Bolt_Upright]

I am not smart enough to understand this paper or the study that started all of this

[Bolt_Upright in reply to Bolt_Upright]

I have decided that I don't have to understand this report on Niacin and 2PY. I believe in Nicotinic Acid, so I would keep taking it regardless of the concern.

[MarionP in reply to Bolt_Upright]

That first criticism of yours, the principle is called reverse causality, I don't know if I will be able to access the original article but for anybody who does, "reverse causality" is when there is an initial selection bias in the subjects chosen, which invalidates the study... By picking people who are in some ways sick or otherwise affected such that they are the ones most likely to seek out or demonstrate the experimental variable under question, without sufficient control groups to counter the bias. Thus instead of the hypothesized variable causing the illness result, it was actually the illness result that caused the subject to be in the group selected as a subject. That's the scientist goes out claiming A caused B when it was actually B caused A, and is one of the reasons that it's important to demand independent replication instead of making conclusions from a single study, rather than just be batted about untrained or unethical journalists or authors like a butterfly in the winds of variability, X was the result of the day but the next day the results are the opposite, negative X, causing confusion and panic in the general public who just trust, which most of us have no choice but to do.

[Bolt_Upright]

You have done me a great service Jack! I have someone close to me that I did not think could handle the flush of Nicotinic Acid, so I recommended Nicotinamide. Nicotinamide is supposed to be "naturally" flush free. After reading these articles and that reddit post I know to steer people away from Nicotinamide and other long acting versions.

Thanks!

[chartist]

A little perspective.

People with PD are already at increased risk for cardiovascular disease and I previously wrote about that here and a way to help that situation with melatonin :

healthunlocked.com/cure-par...

More recent studies of melatonin further confirm what I wrote 3 years ago, such as this 2023 review of newer studies :

sciencedirect.com/science/a...

Here is a relevant quote :

' Melatonin, a natural antioxidant, has been shown to inhibit oxidative stress and stabilize endothelial function, providing cardiovascular protection. The clinical application of melatonin in the prevention and treatment of CVDs has received widespread attention. In this review, based on bibliometric studies, we first discussed the relationship between oxidative stress-induced endothelial dysfunction and CVDs, then summarized the role of melatonin in the treatment of atherosclerosis, hypertension, myocardial ischemia-reperfusion injury, and other CVDs. Finally, the potential clinical use of melatonin in the treatment of these diseases is discussed. '

The above review is very useful because it highlights that melatonin starts at or near the beginning of atherosclerosis by inhibiting oxidative stress and stabilizing vascular endothelial function. Is it just a coincidence that atherosclerosis often starts in the teens or 20's when melatonin levels are on a sharp declining trajectory?

I'm sure there are many things which we consume or are exposed to that may contribute to vascular inflammation and endothelial oxidative stress and I don't think it is possible or practical for us to know every single possibility or cause. Add in melatonin's anti inflammatory effects and that seems like a very good starting point in preventing atherosclerosis in the first place or trying to treat existing atherosclerosis.

On that note, melatonin has shown effectiveness at reducing vascular inflammation and the resulting atherosclerosis followed by the resulting cardiovascular diseases (CVD), the number one cause of death in the world, which accounts for over 30% of deaths in the world each year or about 18 million people per year. This very significantly dwarfs in just one year, the estimated 7 million people to have died from Covid-19 since Covid-19 was discovered and tracked in 2019/2020 to today. This gives a better idea of just how serious atherosclerosis is for all of us.

It is just my opinion, but rather than spend time on what this study suggests as just one potential contributor to atherosclerosis, it might be a bit less time consuming and more time effective in focusing more on trying to stop atherosclerosis and CVD through avenues that are already discovered and accessible to most of us.

Another very common supplement that helps alter the course of atherosclerosis and can significantly work against atherosclerosis is Grape Seed Proanthocyanidin Extract (GSPE). This study using a relatively low dose of GSPE appears to effectively alter the trend of atherosclerosis from gradually upward to gradually downward :

ncbi.nlm.nih.gov/pmc/articl...

Here is a relevant study quote :

' GSPE inhibited the progression of MMCIMT and reduced carotid plaque size in GSPE treated patients, and with extended treatment, the superior efficacy on MMCIMT and carotid plaque occurred. Furthermore, the GSPE group showed lower rates of clinical vascular events. '

See attached graph for a good visual of the effects of GSPE on atherosclerosis .

So these two supplements not only work against atherosclerosis, they confer other potential health benefits with regular use. These two supplements are part of my plan to reverse atherosclerosis.

Art

The positive effects of GSPE on atherosclerosis.

[JackBruce2024 in reply to chartist]

Thanks for this very useful information, Art

[MarionP in reply to chartist]

I'm going to add that to my conversation with my cardiologist next August.

[chartist in reply to MarionP]

It might be helpful to take the studies with you or email /MyChart them to your doctor in advance of your visit for review prior to the visit or do both.

Art

[MarionP in reply to chartist]

👍

[Rufous2]

I don't have a dog in this fight, but thought it should be mentioned that high doses of niacin (nicotinic acid, not just niacinamide) can damage the liver. Here's a short clip by Chris Masterjohn on preventing that damage if one is compelled to take large amounts of niacin in any form, for any reason;

google.com/search?client=sa...

BTW.... CM doesn't work for "Big Pharma" and he doesn't sell products.

[Gioc in reply to Rufous2]

“Big pharma" on the other hand sells vitamin B3 niacin in a patented form for cholesterol, but doesn't advertise it much also because pure B3 niacin has a negligible cost and works the same, perhaps better. But everyone in the industry knows this, it's strange that CM doesn't mention this fact.( side effects are indicated in the drug leaflet)

en.m.wikipedia.org/wiki/Aci....

[Esperanto]

Also trials in 2011 and 2014 concluded that adding niacin to statin therapy did not provide additional clinical benefits, although it has been used for coronary heart disease prevention for over 40 years, showing reduction in clinical events and lesion improvement. The research below also questioned the outcomes of these trials. They concluded that it is important to consider the formulation, dose, and timing of niacin for optimal results and to avoid potential unexpected cardiovascular outcomes.

Niacin and heart disease prevention: Engraving its tombstone is a mistake

Harold Robert Superko et al. J Clin Lipidol. 2017 Nov-Dec.

pubmed.ncbi.nlm.nih.gov/289...

The (too) high dosages used in these studies of more than 2000mg can also lead to unwanted effects. A dose of niacin from 1000 mg per day can significantly increase homocysteine levels; giving vitamin B6 alongside niacin prevents an increase in homocysteine levels. Even better is to take B3 in combination with a vitamin B complex, because B-vitamins work together to a high degree.