NAD+ is a coenzyme, or helper molecule, that remediates fundamental metabolic functions; the Krebs cycle, glycolysis, fatty acid oxidation, gluconeogenesis and hormonal synthesis.
While it’s essential for optimal health, research shows that NAD+ levels continue to fall with age. Low NAD+ levels are linked with accelerated ageing and a variety of harmful diseases (1, 3).
Cellular NAD+ levels oscillate in a circadian rhythm in the liver and body-wide, which is largely defined by our sleep and nutrition. NAD+ appears to have a strong role in regulating circadian clock-controlled expression of metabolic genes.
Consuming NAD+ directly will result in hypoglycaemic episodes, so one way to raise NAD+ levels safely is to consume NAD+ precursors — the building blocks of NAD+ — like nicotinamide riboside (NR).
Animal studies show that nicotinamide riboside raises blood NAD+ levels by up to 270%. What’s more, it’s more readily used by your body than other NAD+ precursors (7).
Activates Enzymes That Slow Ageing
When Nicotinamide riboside increases NAD+ levels in your body, it activates certain enzymes that slow the ageing process.
One group is sirtuins, which appear to improve lifespan and overall health in animals. Studies indicate that sirtuins may repair damaged DNA. It is best to conceptualise ageing as ‘information loss’, as the base blueprint for the body (DNA) decays over time.
Sirtuins also boost stress resistance, reduce inflammation and offer other benefits that promote healthy ageing (9, 10, 11).
Sirtuins are also responsible for the lifespan-extending benefits of calorie restriction (12). In some ways NR mimics the physiological effects of fasting.
Another group NR activates is Poly (ADP-Ribose) polymerases (PARPs), which repair damaged DNA. Studies link higher PARP activity to less DNA damage and a longer lifespan (13, 14).
May Assist in Weight Loss
Four nicotinamide adenine dinucleotide (NAD) coenzymes, namely NAD+, NADH, NADP+, and NADPH, mediate the key transformations from food into energy, activity, biomass, and repair (1).
The NAD metabolome is disturbed by several conditions of metabolic stress in multiple tissues. In the liver of overfed mice, NAD+, the key catalyst for fuel oxidation, is modestly depressed whereas levels of NADP+ and NADPH, the key catalysts for nucleic acid and lipid biosynthesis and control of reactive oxygen species, are greatly depressed (2).
Nicotinamide riboside acts through the nicotinamide ribose kinase pathway to replete the NAD metabolome (3) in a manner that is bioenergetically less costly than other routes to NAD (4). In male mice, NR blunts weight gain on a high fat diet and simultaneously improves multiple metabolic parameters (2, 5).
However, research has not established whether any of these mechanisms are addressable in common human obesity and over what time frames, and whether there are sex differences in responses to NR.
A new trial published in this issue of the American Journal of Clinical Nutrition deployed 1 g of NR/d for 6 wk in 13 overweight or obese men and women (9). The trial was placebo-controlled and featured a crossover design such that every participant had 6 wk of NR followed by 6 wk of placebo or vice versa.
The authors discovered that body composition was altered with a 1.34% reduction in the percentage of fat mass (P = 0.02) (9). The drop in fat mass was accompanied by an increase in fat-free mass (lean mass was not measured) and an increase in sleeping metabolic rate observed in 6 of 7 female participants.
Though the trial was small and had a short time frame, it provided 2 easily measured biomarkers of NR-responsiveness: a change in body composition, which was measured by whole-body densitometry, and an increase in skeletal muscle acetylcarnitine
May Help Protect Brain Cells
NAD+ plays a key role in helping your brain cells age well, functioning like a mild nootropic.
Within brain cells, NAD+ helps control the production of PGC-1-alpha, a protein that appears to help protect cells against oxidative stress and impaired mitochondrial function (15).
Researchers believe both oxidative stress and impaired mitochondrial function are linked to age-related brain disorders such as Alzheimer’s and Parkinson’s disease (16, 17, 18).
In mice with Alzheimer’s disease, nicotinamide riboside raised brain NAD+ levels and PGC-1-alpha production by up to 70% and 50%, respectively. By the end of the study, the mice performed significantly better in memory-based tasks (4).
In a test-tube study, nicotinamide riboside raised NAD+ levels and significantly improved mitochondrial function in stem cells taken from a Parkinson’s disease patient (19).
However, it’s still not clear how helpful it is to raise NAD+ levels in people with age-related brain disorders. More human studies are needed.
May Lower Heart Disease Risk
Aging is a major risk factor for heart disease, which is the world’s leading cause of death (20).
It can cause blood vessels like your aorta to become thicker, stiffer and less flexible.
Such changes can raise blood pressure levels and make your heart work harder.
In animals, raising NAD+ helped reverse age-related changes to arteries (21).
In humans, nicotinamide riboside raised NAD+ levels, helped reduce stiffness in the aorta and lowered systolic blood pressure in adults at risk of high blood pressure (22).
That said, more human research is needed.
Other Potential Benefits
In addition, nicotinamide riboside may provide several other benefits:
- May aid weight loss: Nicotinamide riboside helped speed up the metabolism of mice. However, it’s unclear whether it would have the same effect in humans and how strong this effect really is (23).
- May lower cancer risk: High NAD+ levels help protect against DNA damage and oxidative stress, which are linked to cancer development (24, 25).
- May help treat jet lag: NAD+ helps regulate your body’s internal clock, so taking niagen may help treat jet lag or other circadian rhythm disorders by resetting your body’s internal clock (26).
- May promote healthy muscle aging: Raising NAD+ levels helped improve muscle function, strength and endurance in older mice (5, 27).
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