The below paragraphs were taken from the first part of a two-part World at Large story on NAD+ supplementation.

Since the turn of the century the progress in the field of longevity has been remarkable. Researchers like Dr. David Sinclair, Dr. Rhonda Patrick, Dr. Eric Verdin, and others have catapulted the field from one that was secondary to other lifespan-focused fields like those related to helping cancer, diabetes or other common killers, into one of the most exciting and interdisciplinary areas of study today.

Along with research into simple lifestyle interventions like sleep, exercise, and sauna use, certain specific nutritional elements, notably a select few known as “NAD+ boosters,” are being looked at and now commercially sold, as potentially effective treatments for a disease that’s very old but also very new: aging.

NAD+ boosters like nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN), as well as the compound resveratrol – produced in plants, notably red grapes, during periods of stress can all be purchased in supplement form commercially.

What exactly does a longevity supplement do for you? So far the ever-expanding field of longevity research has come up with a shopping list of benefits from reducing age-related decline of the eyes, to all-cause mortality.

Nicotinamide riboside

Of all the NAD+ boosters – compounds which either convert directly into, or contribute in some way to the process of creating NAD+, nicotinamide riboside (NR) has been the most extensively studied – mostly in animals.

In rodent studies, NR has been shown to have a variety of different effects desirable for different people looking for different things. In one study, mice who were fed a diet high in both sugar and fat in order to quickly create obesity, gained less body fat and demonstrated increased insulin sensitivity when taking an orally administered dose of NR.

Mice receiving the same size dose of NR as the obesity study (400mg per kilo of body weight) were also found in another study to have reversed mitochondrial damage and increased mitochondrial biogenesis, the process through which mitochondria are created.

Finally, neurological benefits from NR supplementation were also confirmed in rodents, including neurogenesis, synaptic plasticity, and reduced beta-amyloid buildup in the brain, a strong indicator of Alzheimer’s risk.

“Whether taking nicotinamide riboside will have the same effects on delaying aging or improving mitochondrial function in humans as it does in animals is unknown,” writes famed longevity expert Dr. Rhonda Patrick on her blog.

“However, when people with type 2 diabetes took a nicotinic acid derivative (an NAD+ precursor), they exhibited improvements in mitochondrial function in their skeletal muscle as well as increased NAD+ levels in their muscles”.

Nicotinamide mononucleotide

While not studied as thoroughly as NR, nicotinamide mononucleotide (NMN) has also been shown to aid in longevity.

“Animal studies have shown nicotinamide mononucleotide administration to be effective in increasing NAD+ levels across multiple tissues while improving the outcome of a variety of age-related diseases in multiple rodent studies,” Rhonda continues.

In separate mouse studies, injections of 500mg per kilo of bodyweight were found to have beneficial effects in countering symptoms of obesity, particularly in improving insulin sensitivity and NAD+ levels in the liver and muscle, and also several markers of cardiovascular disease related to dysfunction of the heart.

Levels of NAD+ decrease across all tissues over time, which experts believe is a key factor in age-related tissue decline in the muscles, heart, brain, liver, and other organs. Starting at 5 months of age, a mouse cohort was split into two groups and fed a diet that included 100 and 300 mg per kilo of body weight of NMN for 12 months respectively.

“The mice that were fed nicotinamide mononucleotide had improved skeletal muscle mitochondrial function, increased energy expenditure, increased bone density and decreased insulin resistance in a dose-dependent manner,” writes Rhonda. Dose dependency refers to the amount of NMN consumed relating to the gravitas of the observed effect.

For instance, in the case of the mouse cohort, the 100mg group of NMN in the diet resulted in a 4% reduction in age-associated weight gain, while the 300mg group experienced a 9% reduction. Remarkably, it was also shown to increase or fortify energy metabolism, eye function, and insulin sensitivity, while reducing age-associated gene expression.

Resveratrol

Short of your bartender explaining to you why this or that particular bottle of red wine is good for your heart, resveratrol is only recently beginning to be explored as a potential longevity compound. It exists in the seeds, fruits, skins, leaves, stems, and other parts of a variety of plants, and is expressed therein during periods of stress on the plant.

This is why red wine is noted as having heart-healthy or antioxidant effects on the body. During the winemaking process, the stressed parts of the grape confer resveratrol into the beverage, however it’s likely negligible amounts.

In a study where healthy individuals were given a 6-week course of 40mg of resveratrol derived from the extract of a plant called Japanese knotweed, multiple anti-inflammatory effects were observed. Reductions in pro-inflammatory markers such as the expression of pro-inflammatory cytokines TNF-Alpha and IL-6, as well as the concentrations of reactive oxygen species were noted after the trial.

IL-6 and TNF-Alpha are significant hindrances in longevity, with TNF-Alpha being correlated with every disease known to man.

The most significant way in which resveratrol acts to improve longevity is through sirtuin activation. World at Large reported on Monday: “Sirtuins use NAD+ to control the genes involved in some of the most critical systems in our biology including energy metabolism, circadian rhythms, autophagy, DNA repair, and cell survival…”.

Sirtuins also play a role in insulin release, lipid mobilization, stress responses, and lifespan modulation, and expression of sirtuins has been shown to mimic many of the beneficial effects observed in calorie restriction, another longevity-based field of research.

Dr. Patrick explains on her website how caloric restriction has been widely shown to increase healthspan and lifespan in organisms from bacteria to primates.

A study in Nature reports just that, explaining their finding that in yeast, “resveratrol mimics calorie restriction by stimulating sirtuin-2, increasing DNA stability and extending lifespan by 70%.”

Taking resveratrol in supplement form must be done with a little more application than other supplements. Dr. Patrick has collected much of the resveratrol research on her website, including how the bioavailability of resveratrol was shown to be higher with a moderate-fat breakfast than with a high-fat breakfast and how resveratrol is safe in humans in doses as high as 5 grams.

Finally, in a conversation Dr. Patrick had with Harvard Professor of Genetics Dr. David Sinclair, the latter recommends the storing of resveratrol in a cold dark environment at all times. WaL

Continue exploring this topic — Maybe You’ve Heard of NAD+: Here’s Why it’s Important and Why Everyone’s Talking About