Mitochondrial Health Part 3 – N.A.D., The Anti-Aging Molecule
In the world of anti-aging research, there has been a large focus on N.A.D. which is
a natural compound in all cells of our body. It is a critical molecule in that it helps
cells unlock energy from food and create ATP, a process that occurs in the mitochondria. It is also a signaling molecule to tell cells it needs repair and maintenance. N.A.D. is high when we are young, and declines throughout life by a factor of 50% every 20 years. If you could keep your N.A.D. levels elevated, you could theoretically pause or even reverse signs and symptoms of aging.
N.A.D. stands for nicotinamide adenine dinucleotide. It will be much easier to refer to it as NAD. Made from vitamin B3 (nicotinic acid or nicotinamide/niacinamide) and to a lesser extent from tryptophan. NAD exists as NAD+, NADH, NADP+, and NADPH. NAD is a redox couple where the NAD+ and NADP+ are the oxidized forms and NADH and NADPH are in the reduced form. When oxidized, it loses electrons and when reduced it is gaining electrons and NAD in these coenzyme forms are responsible for all metabolic transformations that take place within our bodies. Without them we would die within 30 seconds. This is how cyanide works. Cyanide shuts down the cytochrome c oxidase enzyme in the mitochondria which is the last step in the process of making ATP and oxygen. Cyanide makes oxygen unavailable.
In the early part of the 20th century, Pellagra a disease characterized by diarrhea, diabetes, delusions and mental confusion, dementia, and death was becoming a severe problem, especially in the southern U.S. where about three million people were suffering with this disease soon after a new refining process for grains had begun. It was a mystery as to what was causing Pellagra and the government dispatched Dr. Joseph Goldberger in 1915 to study the disease. Goldberger realized something was missing from the diet in those who had Pellegra that was in in meat and milk, and he called it
P-P factor or “pellagra-preventative factor.” Nicotinic acid was discovered by Casimir Funk in 1912. He had isolated it from yeast and rice polishing but it was not until 1937 when Conrad Arnold Elvehjem discovered the chemical structure of the P-P factor that it was determined that nicotinic acid and nicotinamide was the deficiency they sought for two decades. After this discovery, grain products with wheat and corn were enriched with either nicotinic acid or nicotinamide to ensure the elimination of Pellagra.
In 2004 Charles Brenner PhD discovered a new form niacin in the body called Nicotinamide Riboside (NR). This form of niacin was more adept at boosting NAD against reactive oxidative stress (ROS), does not cause skin flushing, (which regular niacin will). There have been 74 studies using NR to evaluate its effectiveness for a variety of health conditions. Another form of niacin called Nicotinamide Mononucleotide (NMN) which some sources claim to be more helpful in increasing NAD because it requires one less step in the conversion process to make NAD. David Sinclair PhD is one of them, and there are studies supporting NMN’s treatment of many conditions too. What most do not realize is that NMN converts into NR before it enters the cell so it may not matter what form you start out with. Absorption of both may depend on how well your digestive tract is functioning. The various forms of niacin names can be confusing. This article helps clear this up.
Nichola Conlon PhD has been studying NAD and while she agrees that precursors such as NR and NMN can increase NAD production, in her experiments increasing emphasis on recycling of NAD had a much better effect on overall NAD levels. According to Conlon, there are two pathways that are as equally important as supplying precursors such as NR and NMN. She talks about inhibiting the CD38 enzyme pathway which limits DNA damage and increasing the NAMPT pathway which is responsible for recycling NAD. She has developed a supplement called Nuchido Time+ which has components in it such as ECGC found in green tea, along with black pepper, parsley and the flowers of the Sophora Japonica tree along with nicotinamide to increase the NAMPT pathway. Conlon’s study showed a 242% increase in NAD over 16 days between two participants.
Final Thoughts
A decrease in energy, cognitive abilities, and memory as we age could be a sign of decreasing NAD levels due to diminishing mitochondrial function. With the enrichment of foods with nicotinic acid and nicotinamide, and readily available tryptophan, you would think that our diets would have enough precursors to provide us with adequate amounts of NAD, but it may be that there are too many lifestyle and environmental stressors interfering with this process.
Various companies make NR or NMN that you can take supplementally a dose between 300-1000 mg per day divided between three meals. However, NR and NMN may tax the methylation detoxification pathway of the liver. Scientists recommend that people taking NMN drink bone broth (a rich source of glycine) or take supplemental methyl donors in the form of trimethyl glycine (TMG or betaine) with a dose of 50% to what your NR or NMN dose is to reduce this loss of methyl donor stress to the liver. Lifestyle changes to improve the recycling pathways that Dr. Conlon refers to should include exercise and intermittent fasting. This helps the mitochondria rejuvenate and function better at recycling NAD. Therapies such as infrared light, and PEMF, will do so too. Following Conlon’s research, it would be helpful to include drinking green tea, eating parsley, and using black pepper as a regular part of your dietary protocols. There are other supplements that might help increase NAD production but that I could discuss in another newsletter.
Some clinics are using NAD intravenously to rejuvenate the body. There are scientific debates whether the body can utilize NAD because of its large molecular size and its instability as a redox compound. The infusion takes five to six hours (faster infusions have more symptomatic side effects) with repeated visits before anecdotally people say it helps. I think I would avoid this form of treatment until more information becomes available. Rather than intravenous NAD, intravenous NR or NMN would have less side effects.
I agree with Chris Masterjohn PhD that oral supplementation with either NR or NMN with some added trimethyl glycine or resveratrol seems like the best first step if someone is looking to try and see if it works for them.
