Spotlight: NAD+
Most people haven’t heard of this one - nicotinamide adenine dinucleotide (NAD+). It’s a mouthful, right? But, it’s making waves in the health and wellness industry as the new anti-aging nutrient/supplement. There are studies (animal and human) that show that it can be support:
Cardiovascular health
Cognitive, neural, and brain health
Nerve pain
Mental-emotional balance
Blood glucose balancing
Liver conditions
Lung health
Healthy DNA replication
Metabolic disease
First off, what IS NAD+?
NAD+ is a cofactor that plays roles in various biochemical reactions in the body. It is commonly found in energy-producing reactions in cells - particularly in the mitochondria with ATP production. Studies also show that NAD+ plays a role in biochemical process called posttranslational modification - basically how proteins and enzymes are remodeled right after they are made from DNA. Think of posttranslational modification as the editing and refining process of newly-made enzymes and proteins. Well, NAD+ and posttranslational modification are related through a class of proteins called Sirtuins. Sirtuins are vital in mammals since they influence so many biochemical processes, such as mitochondrial regeneration, fat metabolism, insulin secretion, inflammation, and cellular death.
So, Where do you get it?
Well, you can’t supplement NAD+ directly. The body needs to make it from various nutrients through various biochemical pathways. It can be made through tryptophan, theoretically. But, the process isn’t really robust since the body chooses to use tryptophan for other things than making NAD+. So, the best way to get NAD+ is through other precursors, such as nicotinic acid, nicotinamide, nicotinoamide riboside, and nicotinamide mononucleotide. Scope out this picture from Elhassan, et. al below to see the cool biochemical process to make NAD+:
And yup, as you can see from the pathways above, there are nutrients that can enhance the production of NAD+ from these precursors. As you can see with nicotinamide supplementation, resveratrol and leucine can enhance the production of nicotinamide mononucleotide, which can then be pushed towards NAD+ production. So, cool right?
Now, I’m reading your mind, and it’s now thinking what are the therapeutic dosages and what the possible side effects are. Am I right?
Precursor supplementation
Nicotinic acid
Has been used for decades to help control high cholesterol and has been shown to be more effective than nicotinamide in most situations when concerning NAD+. But can cause some adverse effects then done at therapeutic dosages, such as redness and flushing through prostaglandin-mediated vasodilation. And at these dosages, it can harm liver cells - meaning that regular liver enzyme testing is warranted when therapeutically supplementing with nicotinic acid.
Nicotinamide
Animal studies show that this precursor form is less useful compared to nicotinic acid. However, animal models indicate that nicotinoamide is favored over nicotinic acid when animals were fed high-fat diets since high-fat diets + nicotinamide mononucleotide supplementation led to increased sirtuin activity. Unlike nicotinic acid, nicotinamide does not activate prostaglandin-mediated vasodilation, and therefore does not cause flushing. Safety-wise, animal models have shown that it can cause liver and kidney toxicity.
Nicotinamide riboside
Literature indicates the high bioavaiblity of nicotinamide riboside, and that blood levels of NAD+ rise in a dose-dependent manner. Basically meaning that the more of nicotinamide riboside that is given, more NAD+ will end up in the blood. Nicotinamide riboside supplementation has also been shown to support neuron NAD+ synthesis compared to nicotinic acid and nicotinamide. Since nicotinamide riboside has a similar chemical backbone structure as nicotinamide, it should not cause flushing via prostaglandin-mediated vasodilation. Safety wise, studies indicate that nicotinamide riboside has a similar toxicity profile to nicotinamide with the liver and kidneys when studied in animal models.
Nicotinamide mononucleotide
There is currently little literature on nicotinamide mononucleotide, but preliminary evidence indicates that nicotinamide mononucleotide can increase NAD+ in animal models. And a study completed by Yoshino et. al revealed that nicotinamide mononucleotide supplementation can enhance insulin sensitivity and inflammation through NAD+-activated Sirtuins.
NAD+ and Autoimmunity
A specific type of sirtuin, Sirtuin 1, can have a potential role in autoimmunity. Remember how I spoke about how NAD+ can increase the activity of sirtuins? Well, it can also increase the activity of Sirtuin 1, which can increase the activity of T-helper 17 cells (a type of white blood cells) and can increase risk of developing autoimmune conditions in those who are susceptible. Crazy, right? BUT, T-helper 17 cells can also protect autoimmunity. So, it’s a careful balance between causing autoimmune disease or protecting autoimmune disease. So, if you have a family history of autoimmune conditions, it will be best to consult a naturopathic doctor to see what your options are for your health and wellness goals.
NAD+ Takeaways
As the health and wellness industry is moving from the adaptogenic sphere into the nootropic sphere, I think that knowing about NAD+ and its precursors will empower you to made the best choices for your health goals and your body (PS, nootropic means drugs/substances that can improve brain function, memory, and creativity). And as the market shift is happening, I’m more than sure you’ll be hearing more and more about NAD+ and will now be able to speak about it with friends, family, and your doctor. It’s also pretty cool to know that there are more superior supplementation methods to increase NAD+, but it should always be done under the supervision of a licensed naturopathic doctor because of possible adverse effects related to liver, kidney, and autoimmune health.
To upgrade your mental and cognitive wellness or just overall wellness, we can always help you out at Jupiter Naturopathic Wellness. At the end of the day, the body is the sum of its parts, and we look at your symptoms as a sign from many parts of the body to find the root cause of your issues. We don’t just treat the symptoms since that would be a band-aid to the situation, and more than likely, your symptoms will come back. Depending on the severity of your health and wellness issues, treating the root cause along with treating the symptoms could be the best option. But, treating the root cause will make sure that your symptoms don’t return. Schedule your HSA/FSA-covered initial naturopathic consultation with me at Jupiter today by clicking here.
See ya’ soon at Jupiter!
- Dr. B
References:
Bogan, Katrina L, and Charles Brenner. “Nicotinic Acid, Nicotinamide, and Nicotinamide Riboside: A Molecular Evaluation of NAD+ Precursor Vitamins in Human Nutrition.” Annual Review of Nutrition, vol. 28, no. 1, 2008, pp. 115–130., doi:10.1146/annurev.nutr.28.061807.155443.
Conze, Db, et al. “Safety Assessment of Nicotinamide Riboside, a Form of Vitamin B3.” Human & Experimental Toxicology, vol. 35, no. 11, 2016, pp. 1149–1160., doi:10.1177/0960327115626254.
Dali‐Youcef, Nassim, et al. “Sirtuins: The ‘Magnificent Seven’, Function, Metabolism and Longevity.” Annals of Medicine, vol. 39, no. 5, 2007, pp. 335–345., doi:10.1080/07853890701408194.
Elhassan, Yasir S., et al. “Targeting NAD+ in Metabolic Disease: New Insights Into an Old Molecule.” Journal of the Endocrine Society, vol. 1, no. 7, 2017, pp. 816–835., doi:10.1210/js.2017-00092.
Harijith, Anantha, et al. “The Role of Nicotinamide Adenine Dinucleotide Phosphate Oxidases in Lung Architecture Remodeling.” Antioxidants, vol. 6, no. 4, 2017, p. 104., doi:10.3390/antiox6040104.
Harlan, Benjamin A., et al. “Enhancing NAD+Salvage Pathway Reverts the Toxicity of Primary Astrocytes Expressing Amyotrophic Lateral Sclerosis-Linked Mutant Superoxide Dismutase 1 (SOD1).” Journal of Biological Chemistry, vol. 291, no. 20, 2016, pp. 10836–10846., doi:10.1074/jbc.m115.698779.
Kwon, H.-S., et al. “Three Novel Acetylation Sites in the Foxp3 Transcription Factor Regulate the Suppressive Activity of Regulatory T Cells.” The Journal of Immunology, vol. 188, no. 6, 2012, pp. 2712–2721., doi:10.4049/jimmunol.1100903.
Lim, Hyung W., et al. “SIRT1 Deacetylates RORγt and Enhances Th17 Cell Generation.” The Journal of Experimental Medicine, vol. 212, no. 5, 2015, pp. 607–617., doi:10.1084/jem.20132378.
Loosdregt, J. Van, et al. “Regulation of Treg Functionality by Acetylation-Mediated Foxp3 Protein Stabilization.” Blood, vol. 115, no. 5, 2009, pp. 965–974., doi:10.1182/blood-2009-02-207118.
Trammell, Samuel A. J., et al. “Nicotinamide Riboside Is Uniquely and Orally Bioavailable in Mice and Humans.” Nature Communications, vol. 7, no. 1, 2016, doi:10.1038/ncomms12948.
Xie, Lei, et al. “Protective Effect of Nicotinamide Adenine Dinucleotide (NAD+) against Spinal Cord Ischemia–Reperfusion Injury via Reducing Oxidative Stress-Induced Neuronal Apoptosis.” Journal of Clinical Neuroscience, vol. 36, 2017, pp. 114–119., doi:10.1016/j.jocn.2016.10.038.
Yang, Soo Jin, et al. “Nicotinamide Improves Glucose Metabolism and Affects the Hepatic NAD-Sirtuin Pathway in a Rodent Model of Obesity and Type 2 Diabetes.” The Journal of Nutritional Biochemistry, vol. 25, no. 1, 2014, pp. 66–72., doi:10.1016/j.jnutbio.2013.09.004.
Yang, Tianle, et al. “Syntheses of Nicotinamide Riboside and Derivatives: Effective Agents for Increasing Nicotinamide Adenine Dinucleotide Concentrations in Mammalian Cells.” Journal of Medicinal Chemistry, vol. 50, no. 26, 2007, pp. 6458–6461., doi:10.1021/jm701001c.
Yoshino, Jun, et al. “Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice.” Cell Metabolism, vol. 14, no. 4, 2011, pp. 528–536., doi:10.1016/j.cmet.2011.08.014.
DISCLAIMER: These statements have not been evaluated by the Food and Drug Administration. There are no financial ties to any supplement companies, pharmaceutical companies, or to any of the products mentioned in this post. This post is not meant to treat, cure, prevent, or diagnose conditions or diseases and is meant for educational purposes. As always, please consult your doctor before trying any new treatments or supplements.