A new link of high levels of anti-aging molecule to certain cancers

December 16, 2022

Supplement manufacturing is a multi-billion dollar industry in the United States. Today, you can find a product for just about any health concern. A popular option for those seeking more energy or treatment for age related disorders are NAD+ supplements. NAD+ is a coenzyme (a molecule that helps build other enzymes) involved in cellular processes. It is created in the body by nicotinamide riboside (NR), a form of vitamin B3. Several companies have developed NR supplements such as Elysium Health and Tru Niagen. However, research into side effects is ongoing. According to a new paper published in Biosensors and Bioelectronics, results suggest that NR supplementation could increase cancer prevalence in some cases. Such work highlights the need for personalized recommendation and use.

Unfortunately, NAD+ declines with age starting at middle age. Scientists have linked declining NAD+ levels to age-related issues and diseases such as metabolic dysfunction, diabetes, Alzheimer’s disease, obesity, heart disease, and loss of muscle tone. While there are several ways to boost declining NAD+ levels, only precursor (NR) supplementation shows significant results in clinical trials. Thus, several supplement companies have developed products that deliver the NR precursor, giving the body a chance to convert more NR to  NAD+. However,  there is new concern that one size might not fit all. That is, in certain cases, the precursor (which affects cellular metabolism) may play a role in cancer prevalence.

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Making the connection between NR and Cancer

Scientists on the study developed a new bioluminescence probe that allows for non-invasive imaging of NR uptake in cells. Specifically, they investigated the role of an NR-enriched diet on tumor prevalence and metastases in tumors, focusing on high rates of NR uptake. Mouse models were divided into two groups: one given normal food and the other given NR-enriched food, for two weeks. Then, the researchers inoculated both groups with a breast cancer cell line. By ten weeks, 70% (7 out of 10) of the mice eating high NR food had developed detectable tumors while only 55% (5 out of 9) in the standard food group had them.

They also looked at the rate of tumor metastases, or cancer spread. To do this, the team again divided mice into two groups and gave one group normal food for two weeks and the other an NR-enriched diet. They injected the cancer cells directly into heart muscle and looked for metastases in the whole mouse. They found that 82% (9 out of 11) of the mice eating high NR food had developed brain metastases while only 25% (3 out of 12) of the mice eating normal food developed them. 

The lab continues to experiment with why an NR-enriched diet could lead to increased tumor prevalence and brain metastasis. A hypothesis they put forth in the paper is that supplementation may “fuel metastatic potential of cancer cells or decrease the integrity of the blood brain barrier leading to an enhanced invasion of cancer cells into the brain”.

Limitations and next steps

Something to keep in mind when reading these studies is to consider the relative dose. In this paper the researchers used a very high dose infused into food – 400 mg/kg/day. Current supplements on the market contain orders of magnitude less than that, well within what is currently considered safe consumption. No studies to this date have shown a connection between NAD+ supplements and cancer.

However, the mechanism of NR and increased cancer prevalence and metastasis may be an important component of personalized medicine. For example, doctors may one day advise patients with an increased risk of certain cancers to avoid products containing enhanced NR levels or other precursors of NAD+. 

Other ways to get or maintain NAD+ is through exercise and diet. A 2022 paper published in Nature Aging shows that adults who exercised regularly had NAD+ levels comparable to young adults, suggesting that exercise helps maintain NAD+ levels. Although some NAD+ precursors are obtained from diet, the amount is so small that it does not make up for the amount that naturally declines with age. 

Citation: Maric T, Bazhin A, Khodakivskyi P, Mikhaylov G, Solodnikova E, Yevtodiyenko A, Giordano Attianese GMP, Coukos G, Irving M, Joffraud M, Cantó C, Goun E. A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism. Biosens Bioelectron. 2023 Jan 15;220:114826. doi: 10.1016/j.bios.2022.114826. Epub 2022 Oct 29. PMID: 36371959.

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