With the aging population appetite for health tips and products that can help to guard against the ravages of time has increased. Among the list of hopefuls some have their hopes pinned on nicotinamide adenine dinucleotide which plays important roles in cellular production of energy; NAD+ is the oxidized form which plays roles in metabolic pathways and is involved in other important processes such as DNA repair. With age levels of this important molecule naturally declines which is proposed to contribute to the underlying physiology of aging.
Boosting levels of NAD+ has been shown to extend lifespan in animal, yeast, and worm studies, as well as having promise for improving several other aspects of health; increasing levels in older mice seems to rejuvenate mitochondria, improve cardiovascular function, enhance muscle regeneration, and promote better glucose metabolism with supplementation.
Based on these and other promising findings companies are selling supplements containing NAD+ precursors such as nicotinamide mononucleotide and nicotinamide riboside. NR supplements have attracted attention of 2 major suppliers: Elysium Health and ChromaDex, but the NR business has also attracted criticism as well as dietary supplements are lightly regulated which allows them to be sold before research confirms effectiveness and safety in humans. However, clinical trials are showing adults taking NR for 6-8 weeks are experiencing boosted levels of NAD+ without serious side effects, and researchers from the companies are still working to prove NR can improve human health because not everything that works in animal studies will translate to humans.
Elysium is studying effectiveness of NR in a variety of conditions such as fatty liver and kidney injury and has published a small trail showing potential to slow the neurodegenerative disease amyotrophic lateral sclerosis. ChromaDex is studying NR in a variety of clinical trials including its effects on cognitive function, mood, and sleep in those aged 55+.
NAD+ is also gaining attention in cancer research for different reasons; many forms of cancer cells are suggested to depend on NAD+ to sustain rapid growth, inhibiting supply could be an effective strategy for killing certain forms of cancer. These studies paint a different and more complicated picture of NAD+ bringing about questions and concerns regarding how taking a boosting supplement may influence health.
According to Versha Banerji of the University of Manitoba, “It might still slow down the aging part, but it might fuel the cancer part. We just need to figure out more about the biology of both of those processes, to figure out how we can make people age well and also not get cancer.”
Although more research is needed to fully understand the role(s) NAD+ plays in cancer we should be cautious and keep in mind the potential downsides NAD+ supplementation has shown in animal studies when using it as an approach for anti-aging, according to Rugang Zhang of the Wistar Institute, who’s animal and cell studies inhibiting NAMPT have shown promise in killing cancer cells or enhancing effectiveness of other therapies.
Washington University researchers found among those with glioblastoma tumours those with higher NAMPT levels correlated with shorter survival times in mice studies, when NAMPT was suppressed brain tumor formation was reduced and survival was increased suggesting glioblastoma cells rely on NAMPT and NAD+ in order to thrive.
“There’s a lot of buzz about taking NAD+ precursors for their anti-aging effects, which is based on a lot of great science. I don’t know if taking NAD+ precursors makes existing tumors grow faster, but one implication of our work is that we don’t yet fully understand all of the consequences of enhancing NAD+ levels,” says Albert Kim.
Makers of NR supplements don’t appear to be worried about emerging concerns and questions stemming from animal studies, “I’m not losing sleep over this, reports of higher-than-normal NAMPT levels in cancers do not prove that high NAD+ levels actually promote cancer growth. Whether low NAD+ would block cancer and whether high NAD+ would promote cancer are two separate questions,” says Charles Brenner, chief scientific advisor for ChromaDex who contends that studies that kill cancer cells by suppressing NAD+ producing enzymes don’t properly address the issue.
Zhang’s research was one of the first to directly show supplementation was associated with increased cancerous growths in mice, however, Elysium’s Guarente is skeptical of that data, and postures the study showed a small effect in a small number of animals which has yet to be replicated. “I don’t think the evidence is there at all to say that raising NAD+ levels would favor cancer.”
Currently whether boosting NAD+ levels may fuel cancer growth is a hypothesis based on animal studies, but it has attracted attention as cancer cells have high metabolic needs including some of which that require NAD+. “We know that they like NAD+, but it’s too early to say, if you add NAD+, whether they will grow really fast. Many labs are working to figure that out,” says Shashi Gujar of Dalhousie University.
The answer(s) may not be easy, straightforward, or even a single one as NAD+ is an ubiquitous and fundamental molecule that is involved in many biological pathways and cellular operations. Taking supplements may lead to positive, negative, or a mix of outcomes, the balance may depend upon context as when consumed precursors may be taken up by some tissues more than others, and different cell types are known to employ distinct metabolic programs that can lead to tissue specific responses.
Cancer are diverse in cellular ways like the tissues they arise from, of which some counter the hypothesis of NAD+ fueling cancer, such as inhibiting NAD+ production was key to an errant gene causing DNA damage and tumor formation, in this study feeding NR to the mice helped to protect against the harmful effects.
These findings, when taken together, don’t necessarily point to answers regarding human interests for supplementing, rather they highlight questions for scientists to address. “I would say that given that many people are taking these supplements for health benefits, a study of what these do to cancer risk or existing cancer biology is warranted,” says Matthew Vander Heiden of the Massachusetts Institute of Technology.
“There is tremendous interest in the NAD+ field right now, and I’m pretty sure sooner or later, we will have the evidence to answer this,” says Gujar regarding the need for more evidence.
