Skeletal Muscle NAD+ Levels Are Increased with Nicotinamide Riboside Administration with No Adverse Effects

There are various vitamins available to humans. Fat-soluble vitamins and water-soluble vitamins. Fat-soluble vitamins include Vitamins A, D, E, and K. Water-soluble vitamins include vitamins B and C. Vitamin B has subclasses. Vitamin B 1, 2, 3, 5, 7, 9, 12. The water-soluble vitamins are readily excreted because of their solubility in water, hence, there is a need for regular replacement.

Nicotinamide Adenine Dinucleotide (NAD+)

Nicotinamide Adenine Dinucleotide (NAD+)

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One of the water-soluble vitamins, Vitamin B3, known as Niacin, is a precursor of NAD+, Nicotinamide adenine dinucleotide. NAD+ plays so many important roles in the body. It helps in ATP generation together with flavin adenine dinucleotide (FAD+). They carry high-energy electrons to the electron transport chain (ETC) for ATP generation. It also helps in the maintenance of the integrity of the DNA, regulates the sleep/wake cycle of the body, offers the body protection from diseases and aging effects, and helps the cells to function properly.

NAD+ is also the final product of the breakdown of tryptophan through the kynurenine pathway. It is the oxidized form of NAD. With the addition of a phosphate group, NADPH is formed from NADH, which is a reduced form of NAD.

NAD+ has been reported to be on the decline as organisms age like in mice. However, there is not enough data to support this in humans. NAD+ serves as the compound upon which some enzymes that are involved in the repair of damaged DNA, in the control of key processes in the metabolism of energy, and, the signaling of calcium, act. These enzymes include cyclic ADP ribose synthetase and sirtuin. Thus, NAD plays a role in the physiological functions of the body and the maintenance of DNA integrity.

In mice, blood glucose was lowered, degeneration of the cortical neurons was prevented, and weight gain was reduced when NAD+/NADPH levels were increased using Nicotinamide riboside supplements. Nicotinamide riboside (NR) is a NAD+ precursor that is similar to vitamin B3. Hence, sarcopenia induced by a reduction in NAD+’s production was ameliorated. However, if Nicotinamide riboside can have similar effects in human muscle is not known.

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The effect of Nicotinamide riboside administration in humans

To find out the effect of Nicotinamide riboside on NAD+ in human muscle and the relationship between NAD+ and aging, research was carried out. This research was done by Yasir S.E et al. The study included about 12 healthy men between the ages of 70-80 that received Nicotinamide riboside supplements for 21 days. The men received one gram of oral NR each day for 21 days. 500 grams were taken in the morning and the evening.

Specific metabolites released during cell metabolism were collected and analyzed. The arrangement of the building blocks of the muscle’s RNA was studied also. It was noted that NR caused a reduction in the metabolism of energy and pathways of the mitochondria while supporting the motility and adhesion of cells.

NR supplementation also caused a reduction in inflammation. It decreased the quantity of some inflammatory cytokines like tumor necrosis factor-alpha, and interleukins 2, 5, and 6. This can help to maintain homeostasis in aging, as aging has been associated with chronic inflammation.

The skeletal muscles’ NAD+ levels in the participants were noted to have been on the increase with no harmful effect associated with the supplementation.

In another study by the group, 16 young males and females with an average age of 21, and 11 old males and females with an average age of 69 were studied to determine if there was any deficiency in the brain and skeletal muscle NAD+ content. There was no significant difference between the NAD+ content of the calf muscles in the two groups. Hence, skeletal muscle NAD+ levels do not decline with age.

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Clinical significance

NAD+ is a coenzyme that helps in the energy generation and functioning of the cells. It also serves as a substrate for some important enzymes. Human data on its relationship with aging has been scarce.

Thus, this study shows that NAD+ content of skeletal muscles doesn’t decline with age, and Supplementation with NR increases NAD+ quantity with no harmful effects. Also, NR subserves other additional benefits like reducing chronic inflammation. Thus, it can help to improve the life quality of the aged, since aging is usually associated with chronic inflammation. Thus,  with further research, NR may be useful in the treatment of other chronic inflammatory disorders.

Conclusion

NAD+ is an oxidized form of NAD and is important in energy generation, circadian rhythm regulation, and maintenance of the integrity of DNA. Its levels can be increased by NR supplementation, with additional benefits of reduction of chronic inflammation.

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References

Nicotinamide riboside augments the human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures in aged subjects: a placebo-controlled, randomized trial | bioRxiv

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