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


Senior Member
Cancer detected in both control and suplplemented group

That's not a flaw. I think researchers are trying to create cancer in these tests, so that's part of the design. You use mice that are prone to cancer. Then what you want to observe is whether your test substance, NR in this case, increases the incidence of cancer. Which it did.

They used mice specifically bred to not have a thymus or T cells

I don't know much about mouse models for testing suspected carcinogens, but it may be that this T-cell knockout mouse model is often used for such testing. But I agree that if the main anti-cancer effect of NAD+ is medicated by T-cells, then it may have created an artificial situation by using T-cell knockout mice. So this could be a flaw, admittedly.

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

This is not necessarily a flaw. A high dose given for a short time may be equivalent to a lower dose given for a longer time. Many people taking NR for its assumed longevity effects are taking it daily for years on end.

This will not be the first time that supplements touted to increase longevity have come under scrutiny: decades ago, it was posited that daily antioxidants like vitamin C would increased longevity. But dozens of studies have proven the opposite, that vitamin C supplementation does not increase longevity, and is actually associated with a shortened lifespan.

More recently, longevity enthusiasts started taking C60, only later to discover that this caused cancer in mice, under certain circumstances (when the C60 is exposed to light it becomes carcinogenic).

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

It looks like Science Daily have now updated their title from what was originally:
Popular dietary supplement causes cancer risk, brain metastasis

Popular dietary supplement increases breast cancer risk, brain metastasis, study suggests [Updated]

So I've just added "study suggests" to the title of this thread.
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The study was conducted by U. of Missouri and the misrepresentation of the study by the media stems from a press release put out by an Eric Stan. The U. of Missouri has revised their press release (now by a different author) to better reflect the study findings:

The new title: "Study: New imaging technique in animal study gives insight to popular supplement's potential role in cancer progression"​
(Old press release title: Study: Popular dietary supplement increases breast cancer risk, brain metastasis)

There wasn't anything particularly wrong with the study itself, but what the press release and media portrayed as the findings is where a gross misrepresentation occurred. There was no way for Hip or anyone else to know that the media headlines were off the mark since the full text of the article is not available and the abstract doesn't provide any additional insight into how the authors arrived at their conclusion.

There is no information I could find on whether or not the related compound nicotinamide mononucleotide (NMN) might also increase cancer risk.
The study used MDA-MB-231 breast cancer cells, which are highly dependent on the NAD+ salvage pathway, which is fed by NR and NMN, so I would assume NMN would have the same effect, namely acceleration of triple negative breast cancer dependent on NR in immunodeficient mice.

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.

To me there actually is a distinction. As we know, potential cancer cells arise every day and are eliminated by the immune system. There are many steps between a healthy cell becoming dysplastic, progressing to immune evading cancer cells, and becoming more and more aggressive and undifferentiated like TNBC. To me there is a difference between a substance that initiates cellular mutations/aberrations and one that feeds the energy requirements of an already existing aggressive cancer.

No preclinical study that I am aware of has indicated the NR is oncogenic, rather the literature indicates the opposite based on NRs involvement in immune regulation and DNA repair. In my opinion, even if the results had been significant, injecting mice with aggressive cancer dependent on NR would not indicate that NR causes cancer, bur rather allows the aggressive cell to take hold because it feeds the cancer cell furnace with energy.

Since NAD+ appears to have a role in cancer prevention, my guess is that NR will prove not to be a cancer risk, but could be problematic once a cell has become sufficiently progressed in its mutations to increase NR uptake for use in the NAD+ salvage pathway.

It is possible that a larger study would show that NR supplemented mice develop more cancer once injected with TNBC, but I don't think this study was predictive as a difference of 1.5 mice could easily be due to chance. Nonetheless, given the study design, it would not surprise me if a larger study of the same design showed the NR fed mice developed more TNBC. I would, however, be very surprised if normal mice fed NR developed more cancer over their lifetime than control mice.

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.

Estrogen is an interesting example. One of cellular messages of estrogen is to "proliferate", leading to cellular proliferation of the uterine lining and breasts. Cancer cells mutate to take advantage of this built in messaging. The story is, of course, more complex, with some estrogens and estrogen metabolites having a more protective effect and others being more cancer promoting. Estradiol, estrone, and some of estrogens catechol metabolites are actually thought to be mutagenic in addition to binding to the estrogen alpha-receptor, which is associated with cancer unlike the estrogen beta-receptor.

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.

Given the findings of this study, and other studies, I would agree. It is probably prudent for anyone with cancer, in general, to avoid NR and NMN since we don't have a roadmap or the cancer genomic tests available to determine which cancers will respond positively and which negatively to NR supplementation. Apart from that concerns have been raised that NAD could interfere with oxidative cancer therapies because of its DNA repair mechanisms.


Senior Member
Thanks very much for your incisive and meticulous analysis of the NR study, @Shanti1, most appreciated.
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