NAD⁺ (nicotinamide adenine dinucleotide)

A central electron carrier in energy metabolism and cofactor of a great many enzymes. Studies have observed that the NAD⁺ content of some tissues decreases with age. Sirtuins and enzymes of DNA repair (PARP) use it as a substrate and consume it in the process.

What NAD⁺ does in the body

NAD⁺ is made from niacin (vitamin B3: nicotinic acid and nicotinamide), from precursors such as nicotinamide riboside or from the amino acid tryptophan. It is the most important electron carrier of energy metabolism: in glycolysis, pyruvate dehydrogenase, the citric acid cycle and fatty acid breakdown, NAD⁺ takes up electrons and becomes NADH; in the respiratory chain, NADH passes them to complex I and becomes NAD⁺ again – this flow of electrons drives ATP production. In this process NAD⁺ is not used up but constantly reused. It is used up, however, by enzymes that split it as a substrate: by the sirtuins, which modify proteins and adapt metabolism to the food supply, by the PARP enzymes, which mark DNA damage and initiate repair, and by the immune cell enzyme CD38. The nicotinamide split off in the process is rebuilt into NAD⁺ via a recycling pathway.

Low NAD⁺ – what happens in the body?

With little NAD⁺, fewer electron carriers are available for energy metabolism: glycolysis, the citric acid cycle and fatty acid breakdown slow down, and the respiratory chain receives fewer electrons. At the same time, sirtuins and PARP enzymes have less substrate, so metabolic adaptations and the repair of DNA damage proceed more slowly. Marked niacin deficiency (pellagra) shows in the skin, gut and nervous system – with light-sensitive, inflamed skin, diarrhoea and difficulty concentrating. Even with adequate intake, NAD⁺ can fall when it is used up heavily: studies have observed that with chronic inflammation, extensive DNA damage and with increasing age, more NAD⁺ is broken down by CD38 and PARP.

High NAD⁺ – what does it mean?

High levels show that plenty of NAD⁺ is available for energy metabolism, sirtuins and DNA repair; they usually result from taking niacin or NAD⁺ precursors. For energy metabolism, not only the amount counts but also the ratio of NAD⁺ to NADH: a high NAD⁺ share shows that the respiratory chain is converting NADH back promptly. Very high amounts of nicotinic acid cause skin flushing and can strain the liver, and methyl groups are used up in breaking down surplus nicotinamide.

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