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NAD+ in Aging: Role of Nicotinamide Riboside and Nicotinamide Mononucleotide — Whalespan

Content›Video›NAD+ in Aging: Role of Nicot…

NAD+ in Aging: Role of Nicotinamide Riboside and Nicotinamide Mononucleotide

Rhonda Patrick30m · 2020-01-28

Claims Made

83

Claims Supported

52

Support Rate

63%

Support rate

52 of 83 claims supported

52 supported31 partial / not

Claims from this content

56

✓Well SupportedDNA repair enzymes like PARP use NAD+ as a substrate, contributing to NAD+ decline with age.◐Partially SupportedSupplementing with nicotinamide riboside (NR) increases NAD+ in muscle, derived from liver-produced nicotinamide.✓Well SupportedNAD+ boosters (NR and NMN) at high doses have improved aging in multiple tissues in animal studies.✓Well SupportedDNA damage is a foundational piece of aging, and sirtuins, PARP enzymes, and NAD+ are involved in DNA repair.◐Partially Supported

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Sublingual delivery of NAD+ may bypass oral degradation, making it a potentially more effective delivery method than oral NAD+.

✓Well SupportedNAD+ levels decline dramatically with age.

✓Well SupportedAs individuals age, they lose the ability to produce NAD and consume it more rapidly, with the immune system and DNA repair being significant drains.

◐Partially SupportedThere is evidence supporting nicotinamide riboside (NR) transporter involvement in cellular uptake.

✓Well SupportedSirtuins are enzymes that regulate genes and perform cellular functions including DNA repair, telomere maintenance, mitochondrial health, and inflammation control.

✓Well SupportedSirtuins are NAD-dependent enzymes that consume NAD+ during their activity.

◐Partially SupportedOral nicotinamide riboside (NR) can raise NAD+ levels in whole blood and white blood cells.

◐Partially SupportedThe high doses of nicotinamide mononucleotide (NMN) used in many animal studies are difficult to translate to humans.

✓Well SupportedKetosis can increase NAD+ levels and potentially activate longevity pathways similar to caloric restriction and exercise.

✓Well SupportedOral nicotinamide riboside (NR) is available to cardiac tissue, skeletal muscle, and peripheral nerves.

◐Partially SupportedIntravenously administered NAD+ is likely partially broken down due to unknown cellular uptake mechanisms from the bloodstream.

✓Well SupportedLow cellular energy increases the NAD+/NADH ratio, signaling sirtuin expression and activity.

◐Partially SupportedA human equivalent dose of 400 mg/kg/day of nicotinamide riboside (NR) for animals translates to over two grams per day for a 180-pound man.

✓Well SupportedResveratrol activates sirtuins, which is thought to be the mechanism for its healthspan benefits.

✓Well SupportedNAD+ levels decline dramatically with age, dropping from around 44 units in a 34-year-old to below 1 unit in 80-year-olds.

✓Well SupportedIntravenous administration of NR or NMN allows them to be transported to other tissues and directly form NAD+, bypassing feedback inhibition.

✓Well SupportedNicotinamide riboside (NR) dosing increases whole blood NAD+, which in turn increases respiration (O2) and decreases inflammatory cytokines.

✓Well SupportedBoosting NAD+ may increase lifespan and improve healthspan, with positive data from studies in mice showing lifespan extension.

◐Partially SupportedNAD+ is required for energy production in all tissues, and its decline leads to impaired tissue function.

◐Partially SupportedHigher PARP1 activity is correlated with longer lifespan in mammals.

◐Partially SupportedBoth NR and NMN form nicotinamide, which can be transported into the brain to form NAD+.

◐Partially SupportedNR and NMN can break down into nicotinamide, which may reduce sirtuin activation.

◐Partially SupportedNR and NMN supplements should be kept cold and purchased from manufacturers who ensure they have not been stored in hot conditions.

◐Partially SupportedNicotinamide riboside (NR) has shown positive effects on the brain in animals, including increased neurogenesis.

◐Partially SupportedNAD is essential for metabolism, mitochondrial function, sirtuin activation, and DNA repair.

◐Partially SupportedIn healthy adults aged 60-80, a 250mg daily dose of NR plus pterostilbene reduced diastolic blood pressure and lowered alanine aminotransferase (ALT) levels.

◐Partially SupportedDirect IV injection of NAD+ is an area worth exploring for boosting energy levels in tissues.

◐Partially SupportedDecreased NAD+ levels are associated with hallmarks of aging including loss of proteostasis, mitochondrial dysfunction, glucose intolerance, insulin insensitivity, cellular senescence, and altered epigenetics.

✕Not SupportedNicotinamide inhibits sirtuin activity, which is detrimental for longevity.

◐Partially SupportedNAD+ depletion may increase susceptibility to age-related diseases like Alzheimer's, Parkinson's, cardiovascular disease, muscle atrophy, and infections.

◐Partially SupportedSenescent cells secrete pro-inflammatory molecules and may be influenced by NAD+ in terms of tumorigenic quality.

◐Partially SupportedInjecting NAD+ into mice raised NAD+ levels in brain regions and the heart, and protected against cardiac hypertrophy.

◐Partially SupportedNAD+ is a cofactor for enzymes in mitochondrial energy production and glycolysis.

?Limited ResearchNicotinamide riboside (NR) may show similar cancer-accelerating results as NMN in specific types of cancer driven by pro-inflammatory senescence cells.

◐Partially SupportedNAD+ can be synthesized in the body from dietary sources like tryptophan and the three forms of niacin.

◐Partially SupportedExtracellular NAD+ may be metabolized to nicotinamide, transported to other tissues like muscle, and converted back to NAD+.

◐Partially SupportedNAD+ is crucial for survival, obtained from diet and recycling, but declines with age, leading to metabolic and mitochondrial dysfunction, and increased DNA damage.

◐Partially SupportedNAD+ acts as a cofactor required for enzymes to bind and activate.

◐Partially SupportedCells need to maintain massive concentrations of both NAD+ and NADH for energy production.

◐Partially SupportedNicotinamide mononucleotide (NMN) at high doses in animals can counteract an obesogenic diet, improve metabolic health markers, enhance heart function, and improve cognition and memory.

◐Partially SupportedLong-term dietary administration of NMN in mice with an accelerated aging phenotype mitigated age-associated physiological decline, improving skeletal muscle function, mitochondrial function, energy expenditure, bone density, and decreasing insulin resistance, with benefits occurring in a dose-dependent manner.

◐Partially SupportedBryan Johnson took Tru Niagen (NR) and J Infinity's Vitality (NMN) for 90 days each.

◐Partially SupportedPterostilbene has been found in clinical studies to reduce blood pressure in adults.

◐Partially SupportedThe enzyme converting nicotinamide to NMN is subject to feedback inhibition by NAD+, causing nicotinamide to accumulate when NAD+ levels are high, which can inhibit sirtuins.

◐Partially SupportedNAD+ depletion is associated with decreased autophagy, increased DNA damage, mitochondrial dysfunction, and dysregulated metabolism.

◐Partially SupportedA high dose of NMN for a 180-pound person is approximately 2 grams per day (24 mg/kg body weight).

✕Not SupportedNMN has been shown to accelerate cancer growth in mice with pancreatic cancer where pro-inflammatory senescence cells drive tumor growth.

?Limited ResearchIt is difficult to determine whether NR, pterostilbene, or both were responsible for the observed effects on blood pressure and liver health.

?Limited ResearchNAD+ levels can be increased by exercise, fasting, and NAD+ boosters like NR and NMN.

◐Partially SupportedThe body primarily relies on the NAD salvage pathway to recycle nicotinamide into NAD+.

◐Partially SupportedThe body can produce NAD+ from dietary tryptophan or niacin equivalents, but demand often exceeds production capacity from these sources.

◐Partially SupportedThere is no published evidence of oral NMN supplementation in humans, but two randomized placebo-controlled trials show that NR can increase NAD+ levels in white blood cells in a dose-dependent manner.