Nicotinamide riboside (NR), a form of vitamin B3, may increase risk of breast and brain cancer, study suggests

Hip

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The international team of researchers led by Elena Goun, an associate professor of chemistry at MU, discovered high levels of NR [nicotinamide riboside] could not only increase someone's risk of developing triple-negative breast cancer, but also could cause the cancer to metastasize or spread to the brain.

Once the cancer reaches the brain, the results are deadly because no viable treatment options exist at this time, said Goun, who is the corresponding author on the study.
Source: here

There is no information I could find on whether or not the related compound nicotinamide mononucleotide (NMN) might also increase cancer risk.
 
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Hip

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You're fairly active on Longecity, they've already debunked such fears many times over.
Could you provide a link to any Longecity post where you say they have debunked a possible cancer risk of NMN?

This article about NAD+ precursors like nicotinamide riboside and nicotinamide mononucleotide says:
But NAD+ production (biosynthesis) is often elevated in human cancers, where it plays a critical role in the initiation, progression, and relapse of tumors.
So NAD+ appears to be involved in cancer metabolism. However, the article suggests that the net effect of NMN may be to fight cancer, and also to sensitise tumours to cancer immunotherapy.

Thus it is possible that NMN might have anti-cancer effects. It is also possible that it might promote certain cancers.

This occurs with selenium supplementation: it is protective against many cancers, but promotes prostate cancer.


We may now see more research on NMN and cancer, given the results of this NR study.
 
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Hip

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Both of the main threads on NR and NMN cover that. Or you could go straight to one of the most knowledgeable on the subject.
Knowledgable but not without vested financial interests:
Dr. Sinclair is a co-founder of a company called Metro Biotech, that wants to develop molecules based on NMN to treat aging and aging-related diseases.
Source: here



From the video at 2:30, Dr David Sinclair says:
"In an abundance of caution, if you had a tumour, I would not take NMN, just because we don't know. But if you are healthy, right now, there is no evidence that it should have any negative side effects"
 

GreenEdge

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The hope of increasing NAD+ is what drove me to experiment with taking Niacin (nicotinic acid). It's the safest (has been used in medicine for over 50 years) and cheapest option. In high enough doses it causes skin blushing and stings a little, so don't take it in excess unless of course you want to deliberately dilate your blood vessels.

The now common form of B3 (nicotinamide (niacinamide)) does not cause skin flushing as your body has to convert it to the active form - thereby making it a slow release formula.

And being a water soluble vitamin your body will soon pee out what it doesn't use.
 
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The hope of increasing NAD+ is what drove me to experiment with taking Niacin (nicotinic acid). It's the safest (has been used in medicine for over 50 years) and cheapest option. In high enough doses it causes skin blushing and stings a little, so don't take it in excess unless of course you want to deliberately dilate your blood vessels.

The now common form of B3 (nicotinamide (niacinamide)) does not cause skin flushing as your body has to convert it to the active form - thereby making it a slow release formula.

And being a water soluble vitamin your body will soon pee out what it doesn't use.
I can't remember the reason why, but that doesn't raise NAD+ levels. @Learner1 could tell you why if she's around.
 

Shanti1

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I was able to access the full-text of this study and discovered that the news headlines regarding nicotinamide riboside causing cancer do not match the study findings.

In this study researchers took 19 Swiss Nude Mice, bread to have no thymus gland or mature T-Cells and fed 10 of them a nicotinamide riboside diet and 9 of them the control diet.

They then injected them with a highly aggressive type of breast cancer cell (triple negative), such that each mouse received approximately 1 million cancer cells. Measuring tumor formation in mice injected with breast cancer does not show that nicotinamide riboside (NR) induces “de novo” breast cancer! Apart from that, the results regarding cancer causation were not statistically significant.

The sample size was Extremely small:
  • 7 out of 10 mice in the NR supplemented group formed detectable tumors when injected with cancer cells
  • 5 out of 9 mice in the control group also formed detectable tumors when injected with cancer cells
  • This is a difference of approximately 1.5 mice and it was not statistically significant.

  • The NR dose given (2,500 mg/day human equivalent) is far higher than the oral NR dose typically used by people
  • Out of the available breast cancer cell lines, the researchers chose the one that had higher NR dependance than other cell lines (MDA-MB-231), as opposed to those that were not as reliant on NR. This would help to guarantee some sort of result, but does not reflect the real-world metabolism of many cancers.
  • One of the ways that NAD+ works is by supporting T-Cell function and T-Cell surveillance, which is one of the ways NAD+ helps to promote healthy cell behavior. This crucial NR/NAD mechanism was conveniently eliminated from the experiment, but it is present in real-world situations.
  • NR has been heavily studied in animals, if there was a causal link between cancer formation and NR, it should have been detected in other studies
  • Other studies indicate that NR may promote healthy cell division and behavior (ref), (ref) and it supports immune T cell function and survival.
In my opinion the headline should have read, "Injecting immunodeficient mice with highly aggressive breast cancer cells causes cancer, independent of nicotinamide riboside intake."

The portion of the study regarding increased brain metastasis in mice involved 11 NR fed mice and 12 control mice. The same Swiss Nude Mice were used and the same NAD+ dependent triple negative breast cancer cell line. This portion of the study deserves more consideration as the results were statistically significant and other research has been mixed, with some research showing NR may encourage cancer growth, and other research showing inhibition. In the current study, given the choice of cell line and mice, the results are not surprising, but in the real world, it probably depends on cancer type and individual cancer cell metabolism/genomics.
 
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hapl808

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The sample size was Extremely small:
  • 7 out of 10 mice in the NR supplemented group formed detectable tumors when injected with cancer cells
  • 5 out of 9 mice in the control group also formed detectable tumors when injected with cancer cells
  • This is a difference of approximately 1.5 mice and it was not statistically significant.
Wow, is that really what those ridiculous headlines are based on? It's made big waves - talked to a friend who recently had cancer and she noticed the study.

I couldn't find it on Sci-Hub, any suggestions where to get the full study?

I really hate our system of journals being behind a paywall so you're hearing second or third hand what studies supposedly showed. Which often fall apart if you get to read the study.
 

Shanti1

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I couldn't find it on Sci-Hub, any suggestions where to get the full study?
Hopefully Sci-Hub will have it soon, I had to request it through my work. The study was conducted by the U. of Missouri and whoever wrote their press release is where the misrepresentation started. The media grabbed from the press release, which completely misrepresented the findings.
 

Hip

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I was able to access the full-text of this study
Great job Shanti1!



The sample size was Extremely small:
  • 7 out of 10 mice in the NR supplemented group formed detectable tumors when injected with cancer cells
  • 5 out of 9 mice in the control group also formed detectable tumors when injected with cancer cells
  • This is a difference of approximately 1.5 mice and it was not statistically significant.
It would definitely require a further larger study to see if the effect is statistically significant.



They then injected them with a highly aggressive type of breast cancer cell (triple negative), such that each mouse received approximately 1 million cancer cells. Measuring tumor formation in mice injected with breast cancer does not show that nicotinamide riboside (NR) induces “de novo” breast cancer! Apart from that, the results regarding cancer causation were not statistically significant.
Apparently 15% of breast cancers are the triple negative type, the form of breast cancer tested in this mouse study.

I don't know much about it, but I don't think it matters whether a substance can create a cancer from new (by causing genetic mutations) or whether the substance just promotes cancers; in either case, there may be increased risk of cancer.

For example, high oestrogen is a risk for breast cancer, but oestrogen does not create new cancers itself (oestrogen is not mutagenic), but can promote the multiplication and spread of existing breast cancers. This is why those who have had breast cancer are often given drugs to suppress oestrogen.



One of the ways that NAD+ works is by supporting T-Cell function and T-Cell surveillance, which is one of the ways NAD+ helps to promote healthy cell behavior. This crucial NR/NAD mechanism was conveniently eliminated from the experiment, but it is present in real-world situations.
Yes, it could well be that NR has other mechanisms which are anti-cancer, and the anti-cancer mechanisms could counter-balance the pro-cancer effects.

But certainly anyone who has had triple negative breast cancer in the past might want to consider whether taking NR is a good idea or not.
 
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Knowledgable but not without vested financial interests:
He advocates intermittent fasting and exercise for longevity, both of which cost nothing. It seems a bit rude to suggest that he is only in this for the money.

and the anti-cancer mechanisms could counter-balance the pro-cancer effects.
What pro-cancer effects? Being young?
 

Hip

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It should not be surprising for anyone that a supplement can cause cancer. We already know several supplements which are carcinogenic:

Carcinogenic Vitamins and Supplements:
  • Vitamin E increases the risk of prostate cancer and bladder cancer.
  • Selenium increases the risk of prostate cancer.
  • Folic acid in higher doses has an increased risk for colon cancer.
  • Calcium at more than 1000 mg a day is a cancer risk. 1
  • Beta carotene (vitamin A) is a lung cancer risk for anyone who smokes or has smoked in the past.
  • Vitamin D at higher levels is a risk factor for some cancers. 1
  • Vitamin B12 is a risk for lung cancer. 1

Though note many of these supplement although carcinogenic for some types of cancer, may also be anti-carcinogenic for other forms of cancer. So to understand the overall effect of a supplement on cancer, you have to look at all the studies.
 
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Violeta

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Listing possible supplements that may be carcinogenic at some levels doesn't address the expanded information that reveals the flaws in the study in the original post.
 

Hip

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Listing possible supplements that may be carcinogenic at some levels doesn't address the expanded information that reveals the flaws in the study in the original post.
The study was not flawed as such, but Shanti did a nice job analysing the study, and pointed out that it was just too small to reach statistical significance. That means the finding of a carcinogenic effect of nicotinamide riboside could be correct, but it the finding might also be due to random chance. Only a larger study can address this, ie, a study which uses more mice.

It is normal in research to conduct these small-scale studies first, and then if an effect is found, to conduct a larger study to confirm or refute. If a larger study is performed, then we may have more info.

However, the brain metastasis part of the study was statistically significant. So NR may well promote triple negative breast cancer metastasis to the brain.



I listed the known carcinogenic vitamins just to show that supplements can promote cancer. Some people may think that supplements are always benign, but like everything, they can have their downside. It's better to be informed of these downsides than not.

I take high dose selenium daily, and it does concern me that whilst selenium is protective against many cancers, it promotes the more aggressive forms of prostate cancer. You have about double the risk of dying from these aggressive prostate cancers if you are taking higher doses of selenium. But selenium has such a good effect on my ME/CFS symptoms that I have to balance this risk against the benefits I get for my ME/CFS.
 

Hip

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@Hip, I've read that selenium can cause hair loss. I don't know at what dosage that happens, though. Have you noticed any effects with your hair?
I did notice a slight increase in hair loss somewhere along the line, after I developed ME/CFS about 15 years ago. I started taking high dose selenium daily about 10 years ago, and have not stopped.

So it could be that the hair loss I experience was due to selenium. Or it might just be due to the ME/CFS. I cannot remember the timing of when I first noticed the increased hair loss, so I can't pin it down to one or the other. I use minoxidil anyway to try to counter the hair loss, and find this is reasonably effective.
 

Violeta

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The study was not flawed as such,
Cancer detected in both control and suplplemented group
  • 7 out of 10 mice in the NR supplemented group formed detectable tumors when injected with cancer cells
  • 5 out of 9 mice in the control group also formed detectable tumors when injected with cancer cells
They used mice specifically bred to not have a thymus or T cells
  • One of the ways that NAD+ works is by supporting T-Cell function and T-Cell surveillance, which is one of the ways NAD+ helps to promote healthy cell behavior. This crucial NR/NAD mechanism was conveniently eliminated from the experiment, but it is present in real-world situations.
The dose used was much higher than a normal human dose

The NR dose given (2,500 mg/day human equivalent) is far higher than the oral NR dose typically used by people

The title is misleading:
Nicotinamide riboside (NR), a form of vitamin B3, increases risk of breast and brain cancer

As Shanti said, "In my opinion the headline should have read, "Injecting immunodeficient mice with highly aggressive breast cancer cells causes cancer, independent of nicotinamide riboside intake."