Clinical trials continue to back the popular supplement NMN.
2023… Year of the Water Rabbit, UN International Year of Millets (who knew?) and possibly the year of the supplement. And not just any supplement – nicotinamide mononucleotide, better known as NMN to its friends. Awareness of longevity and healthspan among the public is growing at an incredible rate and so too is the appetite for taking steps to move the needle on youthspan, healthy aging and biological age.
We cover various brands and various compounds on our site, and a great deal of them, quite rightly, focus on increasing NAD+ levels. NMN is important because it is a precursor of NAD+, a molecule that is not only critical for life, but holds great significance for many aging pathways.
Longevity.Technology: Thanks to their impressive results based on numerous animal and cell studies, both NMN and NAD+ have been popular research topics among longevity scientists and leading institutions including Harvard, MIT and the Buck Institute of Aging. It has been encouraging to see a number of significant human studies, as well, supporting the potential of these antiaging compounds, especially given that they are already available on the shelves, rather than drugs like rapamycin, which although is causing a stir in longevity labs, won’t be hitting the healthstore shelves any time soon.
One of the benefits of covering the longevity space is being able to call on experts. When it comes to NMN, we called on Professor Andrew Salzman, a biomedical inventor and Harvard MD, who leads the research at Wonderfeel, a US biosciences company that is striving to move the longevity needle forward with their patented Youngr™ NMN formula. Dr Salzman explained that NAD+ is an essential molecule that is involved in myriad critical cell functions. These include:
- Cell growth and repair, metabolism
- DNA repair and survival
- Cellular respiration, which is the biological process by which our cells take glucose and oxygen, and convert them into energy
- Regulation of gene expression, the process by which our genetic information is used to make amino acids and proteins – the very building blocks of life.
Increasing NAD+ levels translate to improved metabolism and cellular activities which can manifest in a variety of health benefits.
Why not just take NAD+ directly?
An organism cannot survive without NAD+, but NAD+ levels significantly decrease with age, and this decline is associated with the development of age-related diseases such as cardiovascular, neurological and metabolic issues. However, offsetting this decline by NAD+ supplementation is not the answer because, as Dr Salzman explains, NAD+ is not absorbed well by the digestive system, nor is it directly taken up by cells. The upshot of this means that NAD+ alone does not make for a particularly good supplement. It is far better to take an NAD+ precursor – one of the key building blocks – so that your body is able to make vital NAD+ and top up those declining levels.
The precursor NMN is an excellent starting point for the vital molecule that facilitates thousands of reactions for cell energy, DNA repair and stress reduction.
And science bears this out.
NMN: The benefits of this efficient NAD+ precursor
In animal models, taking NMN increases blood NAD+ levels and mitigates age-related diseases.
In humans, NMN enables your body to increase NAD production to youthful levels. This can help ward off all the things associated with getting older. One of the most commonly-described benefits of NMN is that it boosts energy.
People also report prominent relief from aches and pains, quick recovery from hangovers and jet lag and enhanced quality of sleep. Here are some of the further benefits of NMN based on research:
- Improves cognitive function: Studies on Alzheimer’s disease have found that people who take NMN supplements showed improved cognition and memory ; this is most likely due to NAD+ increasing the production of a protein that helps guard cells against oxidative stress.
- Sleep: Sleep is incredibly important for our overall health, playing a role in metabolism, immunity, cognition and memory. A recent study on NMN and sleep found that trial participants’ sleep duration, deep sleep ratio and REM sleep ratios increased when they took NMN, and they reported an improvement in overall sleep quality .
- Extends longevity: NAD activates the sirtuin family of proteins in your cells, which aid in DNA repair. Sirtuin activity contributes to longevity, whereas low NAD levels are linked to age-related diseases that shorten lifespans.
- Reduces the risk of heart disease: NMN has been shown to protect against heart failure in mice . Maintaining higher NAD concentrations in the bloodstream can reverse harm to the arteries that come with age, potentially safeguarding against heart disease.
- Increases insulin sensitivity and reduces metabolic disorders: A small trial looked at the effect of NMN on women with prediabetes and found their muscles’ ability to process sugar improved . Early research is finding that NAD precursors may help reduce body weight, counteract the effects of high-fat diets and improve energy .
- Improves fitness and muscle endurance: Our bones and muscles consume glucose and fatty acids in order to function. NAD+ helps metabolise these into the system. Without it, everything slows down and muscle endurance declines. A recent trial on amateur runners also found that NMN increases physical capacity. Researchers suggest that this is due to enhanced oxygen use in skeletal muscle .
- May lower obesity: Increased levels of NMN activate the metabolic system, which enhances the body’s ability to turn food into energy and can be a tool in reducing the risk of obesity. Nevertheless, this should go hand in hand with an energetic lifestyle and a nutritious diet.
- Promotes organ health: In addition to slowing down aspects of the aging brain, vasculature, muscle, heart, metabolism and eyes, NMN has also been shown to rejuvenate bone stem cells and promote bone formation in rodents. It also reverses intestinal aging, protects against age-related kidney deterioration and inhibits the onset of liver fibrosis in rodents. This suggests that NMN also slows aging in bones, intestines, kidneys and the liver.
- Improves symptoms of serious disease: Researchers are also exploring the specific benefits of increased NAD levels on high blood pressure, liver health and diabetes [7,8,9].
Latest human trial on NMN
The largest human clinical trial to date was recently published in GeroScience . We discussed the preliminary findings with Professor Salzman of Wonderfeel in our interview with him in July.
The peer-reviewed study was authored by Lin Yi, Professor Andrea Maier and Yi’s colleagues from Abinopharm in Connecticut, and it adhered to the most current international standards which were tightly regulated.
The study’s eighty participants were divided into four dosing groups of placebo, 300, 600 and 900 mg. Researchers focused on evaluating three specific markers in study participants at the beginning and conclusion of the 60-day trial which were:
- NAD+ levels in the blood
- Results from an internationally-recognised scoring system of measurement for a person’s overall health
- Performance in a six-minute walking endurance test
The results were promising; firstly, study participants taking NMN performed significantly better than those who received the placebo in all three evaluation categories listed above. Secondly, subjects receiving higher doses, 600 and 900 mg, performed significantly better than those in the 300-mg group, telling us that dosing is key.
Dose dependent results
Wonderfeel evaluated the raw data along with the authors of this study and published their findings about the optimal dosing in an article here.
Backing into the biosciences company’s expertise in NMN and NAD, the Wonderfeel scientists determined 900mg NMN per day, which is further supported by sirtuin-activating compounds in their formula, was the optimal dose based on this clinical trial. Similarly, Professor David Sinclair at the Harvard Medical School, one of the foremost authorities in NMN research, has said that he takes 1000mg NMN per day himself to get the best results from NMN.
While this is the largest human trial to date, since there were 20 participants per dosing group over only a 60-day period, more subjects over a longer testing period would provide more robust meaning to the findings, such as NMN enhancing physical performance and improving overall health parameters.
Research on NMN’s health benefits is currently underway
NMN is also being investigated in clinical trials for specific age-related conditions, such as high blood pressure, metabolic disorders and skin aging [11, 12,13]. The results of another clinical trial about muscle recovery following exercise may shed more light on how NMN promotes muscle function . Adding more clinical data to Yi and his colleagues’ findings will reveal whether NMN’s pro-longevity
FDA restrictions on NMN – taking stock
Those interested in longevity research can hardly have failed to notice the headlines proclaiming an “NMN ban” in the US – but the issue is not nearly as cut and dried as that. Since NMN alleviates age-related ailments in rodents, pharmaceutical companies like Metro International Biotech have investigated it as a human drug .
The consequence of this is that The United States Food & Drug Administration said the popular longevity supplement ingredient beta-nicotinamide mononucleotide (NMN) could not be sold as a dietary supplement in the US. Recently published letters to prospective new suppliers indicate that this is because NMN “has been authorised for investigation as a new drug”. The Council for Responsible Nutrition (CRN), the US trade association for the dietary supplement and functional food industry, has responded, expressing its “dismay” at the ruling.
Due to its being investigated as a drug, NMN may not be sold as a supplement according to the FDA. This development reverses the FDA’s initial decision to approve its sale as a new dietary supplement (NDI). However, many vitamin and supplement companies are continuing to sell NMN while the regulatory process is being evaluated.
Ban is not safety-related
The ban came as a shock to many, especially since its safety or efficacy were not the reasons for the ruling. A company must file an NDI notification with the FDA before a product like NMN can be marketed as a supplement.
The FDA doesn’t have to approve the supplement label, but if they object, this could prevent the compound from being designated as a supplement. NMN has been sold in Asian countries like Japan since 2014, but it is still a newcomer in the United States. The FDA raised objections to numerous NDI notifications filed in the last two years because of a lack of evidence of NMN’s safety.
New studies on NMN’s safety may have alleviated FDA concerns in 2021 and 2022. Accordingly, the FDA accepted without objection an NDI notification from the Chinese company SyncoZymes in May 2022. However, more recently, in response to another NDI notification from Inner Mongolia Kingdomway, the FDA changed its course on granting that company’s NMN an NDI, officially declaring that NMN cannot be marketed as a supplement since it’s already being investigated as a drug .
NMN Market 2023 aims to capture largest share, size and growth forecast until 2027
The NMN Market Report focuses on value chain analysis. North America, Europe and China are the major consumer regions of the global nicotinamide mononucleotide market, among which China is the most significant. In 2019, Chinese consumption accounted for about 67.83 percent of global consumption.
The global nicotinamide mononucleotide (NMN) market was valued at USD 98.5 million in 2019 and it is expected to reach USD 296.5 million by the end of 2026, growing at a CAGR of 7.3 percent during 2021-2027 .
Currently, NMN supplements are still available for purchase online, and the word is people are still stocking up on their go-to supplements.
So, while we’ll be continuing to keep an eye on future FDA decisions, for the moment, we are still confident that NMN is a supplement that can make a real difference to your NAD+ levels, boosting the amount of the important antiaging molecule and promoting healthspan and healthy aging.