I had a patient ask me about the benefits of NAD (Nicotinamide Adenine Dinucleotide). This is another supplement out there that has been in the news lately. What is NAD you might ask? Well, it is a vital coenzyme found in every cell of our body and it plays a key role in the production of energy, DNA repair, and regulating cellular processes. It plays a pivotal role in metabolism and is a co-substrate for enzymes that play key roles in pathways that modify aging. Aging is considered to be an organ-wide loss of homeostasis, innate repair and regenerative capacity resulting in an accumulation of damage and the development of end of life diseases. Obviously, there are multiple changes that trigger the cascade of events that lead to systemic, age related decline and decreased levels of NAD is felt to be responsible for a lot of them. We know that levels decline with age naturally as little as 10% or as much as 80% depending on the individual. NAD decreases with inactivity, high metabolic demand contributing to fatigue, reduced strength and poor endurance. Also, the more damage that occurs to our body results in the use of more NAD being needed for repairs therefore depleting our tank of NAD so to speak.
NAD plays a central role in both metabolic and signaling reactions. It is a co-substrate for two key families of enzymes that affect cellular repair and longevity. The Sirtuins (SIRTs) and the poly(ADP-ribose) PARPs. There is a two fold decrease in these proteins by middle age. When these proteins are activated with increased levels of NAD as well as other methods I have referred to in earlier posts on Hormesis (IF-intermittent fasting, exercise, saunas, cold plunges). They are able to increase cardiac function, increase muscle function, endurance and mitochondrial function, increase vision, memory and skin repair. Overall, it helps our body become more efficient and at the same time giving us more energy, which is what we are all aiming for as we get older.
THE BENEFITS OF INCREASED NAD: It can boost your energy and decrease fatigue by enhancing mitochondrial function and increasing ATP production. NAD supports brain health and cognition by protecting against oxidative stress, reducing neuro-degeneration, decreasing anxiety and elevating one’s mood. It promotes metabolic health by improving insulin sensitivity and therefore decreasing the risk of developing type 2 diabetes. It also helps with achieving optimal weight loss. There are cardiovascular benefits of decreasing blood pressure, arterial stiffness and decreasing inflammation that can affect the cardiovascular system as well as the entire body. It has anti-aging properties by activating sirtuins (enzymes linked to longevity) which support repair and slow the aging processes like cellular senescence by recycling cells that are just using energy and promoting inflammation. NAD also increases muscle strength by production of stem cells enabling the body to recover from the stressors that accompany the aging process as well.
WAYS TO ELEVATE NAD NATURALLY: There are multiple ways to elevate NAD levels. The most important being EXERCISE. This is not shocking and why I always say that exercise is one of the top three things you can do for yourself to ensure a better health span. The most benefit can be seen with HIIT (High Intensity Interval Training) but ANY exercise with help increase you NAD levels. Resistance training (weight, bands), running, cycling or swimming, all are beneficial. The greatest benefits are seen with 150 minutes a week. Just 2.5 hours a week and you are there maximizing your NAD production.
DIET: A diet rich in foods that have B3 (Niacin)-Avocados, peanuts, fish, milk, green vegetables, fermented foods like kimchi and kefir. Healthy fats which include nuts and seeds and limit your intake of sugars, carbohydrates and white flour.
CALORIE RESTRICTION: Again, one of the many benefits of intermittent fasting. I recommend starting with a 12 hour fast for the first 2 weeks then targeting 16-18 hours after that. (It seems like a lot but if you do not eat after dinner and skip breakfast you are already there).
SLEEP: The second most important aspect of living a healthier life. You need to target a minimum of 7 and no more than 9 hours.
REDUCED STRESS: The reduction of both mental and physical stress can result in increased NAD. Primarily but not depleting the stores that the body naturally produces. Avoid physical stressors such as sun exposure and chemical stressors such as alcohol as well as ultraproccessed foods.
SUPPLEMENTAL NAD ELEVATING THERAPIES: Unfortunately, it is not as easy as just taking pure exogenous NAD to replace the deficiency. This does not work due to the fact that it is unstable in nature and its poor bio-availability make it nearly impossible to digest and transfer to most cell types. I know there are longevity practitioners and podcasters that will tell you differently. There are injectable forms and many individuals will go to these clinics and get an IV of NAD, which will increase your levels but temporarily, like for a day, then you are back to where you started because the issue is in the precursors, the beginning process not the end product alone. It is like someone who has a significant bleed in their body and they are low in blood (anemic) so we transfuse them to correct the deficit but until we fix the problem (source of bleeding) we will continue to have a problem.
There are three primary sources of dietary supplements with NAD boosting compounds that are available. NA (Niacin/Nicotinic Acid), NR (Nicotinamide Riboside) and NMN (Nicotinamide Mononucletide). All of these supplements raise NAD levels fairly quickly by as much as 40 to 90% in as little as 2 weeks.
Nicotinic Acid/Niacin (Vitamin B3): This has been one of the first to be discovered to increase your NAD levels but it is generally limited by it side effect of flushing at the doses required to elevate the levels of NAD which is typically 500mg to 1000mg twice a day. This can also benefit your cholesterol panel by decreasing your total cholesterol but mostly your triglycerides. It has also been found to decrease your risk of stroke or heart attacks. To reduce the flushing, you can take a full dose aspirin (325 mg 30 minutes before dosing). I would say only use this supplement if you did not tolerate the NR or NMN.
NMN (Nicotinamide Mononucleotide): This is one of the primary precursors to NAD that is utilized most. Our cells will convert NMN to NAD. It is also found in tiny amounts in food such a 1mg per 100g of broccoli, edamame, cabbage, cucumber or avocado), but the dietary sources are too low to meaningfully raise NAD levels. As a supplement, it is taken orally at doses between 250-1000mg a day to boost NAD more effectively. The optimal dose as far as tolerability and ability to increase NAD was ~600mg so I feel 500mg to 1000mg a day should be fine. The FDA briefly investigated it as a potential drug in 2022 (temporarily restricting sales) because it could not be sold as a dietary supplement but that decision has since changed and it is now readily available.
NR (Nicotinamide Riboside): This is also referred to as niagen which is a specific form of vitamin B3. It is a naturally occurring pyridine nucleoside found in trace amounts in foods such as cows milk and human milk. (So for obvious reasons it not only limited in its naturally available form) but when it is it is in too small of an amount to replenish naturally. It is also a precursor to NAD and is one step upstream of NMN in the NAD salvage pathway . It has been found to be more bio-available than NA or NMN and has been the most studied precursor to NAD. The benefits were found to be optimized at a dose of 500mg twice a day where it was found to increase NAD levels by 60-80% starting at 3 weeks but peaking after 6 weeks. Additional benefits were found when it was taken with pterostilbene, a polyphenol which resembles resveratrol (but has a higher bioavailabilty than resveretrol-80% oral absorption compared to 20% with resveratrol) and acts an NAD booster and functions as a powerful antioxidant and anti-inflammatory agent.
Supplementing with NMN and NR is one of the most reliable ways to restore declining NAD levels as we age. It is maximized when we combine this with lifestyle changes which include, regular exercise (preferably >150 minutes a week, but any exercise is better than no exercise), a healthy diet, calorie restriction with the utilization of intermittent fasting, good sleep of at least 7 hours but no more than 9 hours and reducing the stress in your life (I know, easier said than done).
Both of these precursors raise blood and cellular NAD at least 3 x (or more at higher doses) in human trials, activating the core pathways for mitochondrial energy production, DNA repair and cellular resilience. Pre-clinical research shows clear benefits: better metabolism, reduced inflammation, improved insulin sensitivity, and even lifespan extension in animals. It has also been found to increase your aerobic capacity, sleep quality and subjective well being. (Full disclosure-I was using NMN until 2022 when it was not available for a short period of time then I changed to NR. Being the nerd that I am, I track my sleep regularly with my Oura ring and when I changed to NR my deep sleep increased about 20%!!)
All this being said, large-scale, long term outcomes trials are still limited. NMN and NR reliably recharge your cellular batteries. They show real biochemical promise and are among the safest, most researched longevity supplements available today but their biggest gains come from using them as part of a comprehensive healthy lifestyle. Again, there is no easy way or quick fix but these tools should definitely be in your box to help you have a better health span as we get older. “The longer I live, the more beautiful life becomes.”-Frank Lloyd Wright. Stay healthy my friends.
Doug
