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  • All Roads To Longevity Linked To NAD

    April 13, 2018: by Bill Sardi

    Over a decade ago genetic researchers claimed niacin (vitamin B3), being ubiquitously found in food, serves as a “found-food signal” while resveratrol, a red wine molecule, serves to produce a “food deprivation” signal that mimics a calorie restricted diet.  We were told resveratrol activates the Sirtuin1 survival gene whereas niacin shuts it off.  However, we are now told the niacin derivative NAD boosts Sirtuin1 gene protein levels.

    Fast forward to today.  The target of life-prolonging calorie-restricted diets is NAD –nicotinamide adenine dinucleotide.   Resveratrol is now considered passé.  Niacin derivatives are posed as “beyond resveratrol” pills.   This is despite the fact resveratrol is probably a more powerful NAD booster.

    NAD controls cellular energy metabolism and NAD boosters are being hailed as an anti-aging agent on par or exceeding that of resveratrol.  But is a longevity seeker supposed to simultaneously switch the Sirtuin1 gene on or off or both?

    NAD is essential for the transfer of electrons.  NAD levels decline with age that results in diminished cellular metabolism.  Restoration of NAD to aged animals promotes health and extends lifespan.

    Niacin absorption

    But NAD levels may decline with advancing age for a reason not mentioned commonly in scientific discussions.  Many nutrients such as niacin depend upon stomach (hydrochloric) acid for absorption.  The incidence of low (hypochlorhydria) or absent (achlorhydria) stomach acid secretion is quite common with advancing age and parallels that of aging.  A published study is quite revealing.  Whereas combined studies reveal 0-33% of un-supplemented senior adults were niacin deficient this figure did not improve in supplemented individuals.  This condition affects a growing number of senior adults as they age. One study revealed the incidence of hypochlorhydria at 1.8% in the fifth decade of life and 18.5% in the eighth decade.

    Stomach acid, secreted from parietal cells, is shut off by Helicobacter pylori, a bacterial infection that affects up to half of the adult population.  The prevalence of H. pylori infection increases by ~1% for every year of life, and so 50% of 50 year olds are typically infected.  The overuse of antacids worsens the problem of nutrient malabsorption.

    A striking fact is that niacin is an effective treatment for low stomach acid.  When hydrochloric acid secretion is insufficient, the gastric pH will not be sufficiently acidic, digestion will be impaired, and signs and symptoms of hypochlorhydria will be apparent.  One expert believes inadequate niacin consumption controls the secretion of stomach acid more than aging.

    Niacin stimulates release of histamine and hydrochloric acid secretion.

    Instead of adhering to a daily regimen of designer niacin pills (NR and NMN), maybe supplementation with acid (betaine hydrochloride) or high-dose niacin, possibly as niacinamide (200-500 mg niacinamide), would be more appropriate, not just as a digestive aid, but as an economical anti-aging agent.

    Niacin-like molecules to conquer aging

    Niacin-like molecules such as nicotinamide riboside are being touted as dietary supplements to boost NAD levels.  According to a recent scientific review article in the journal CELL METABOLISM, NAD is in a constant state of synthesis, degradation and recycling.   The forms of niacin from the diet include niacin, niacinamide (non-flush niacin provided in most multivitamins) and NAD precursors nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN).

    While NR and NMN are available from the diet, vast servings of food would need to be consumed just to consume 1 mg of NR or NMN.  So NR and NMN supplements are now promoted.

    High-calorie diets and subsequent obesity reduce NAD levels in tissues.  Obesity and aging result in a 2-fold decrease in NAD levels by middle age.  The consumption of ~15 milligrams of niacin a day maintains NAD levels.  However, NAD levels decline with advancing age and NAD boosters are called for to assuage the premature onset of aging.

    Niacin’s drawback is it induces flushing, but certainly not at the 15-milligram dose needed to maintain health.  High-dose niacin used to reduce cholesterol does induce flushing and slow-release niacin is offered as an alternative. This drawback of niacin is posed as a reason to supplement the diet with the newer NAD boosters.

    Reduction of NAD degradation

    An alternative approach to NAD maintenance is to reduce the degradation of NAD by inhibition of enzymes called PARPs and NADases (p38).  This can be accomplished by low doses of natural molecules like quercetin.   Resveratrol also favorably modulates PARPs and NADases.

    Not just Sirtuin1

    NAD levels are critical for heart health, the heart being a high-energy demand organ.  Sirtuin3, another of the Sirtuin-family survival genes, may actually be the most important NAD signaling protein.  Resveratrol and more so Longevinex have been shown to activate Sirtuin3.

    Niacin from tryptophan

    Niacin can also be synthesized by the liver from the amino acid tryptophan (60 mg tryptophan makes 1 mg niacin).

    The median intake of niacin from food is approximately 41 mg/day for men and 28 mg/day for women, leaving little need for additional synthesis from tryptophan.

    Tryptophan can be found in cheese, chicken, turkey, eggs, fish, milk, nuts, peanuts, bananas, oats, pumpkin seeds, sesame seeds, soy products and tofu.  Rich sources of niacin are poultry, fish, lean meats, nuts, eggs and dairy products.

    However, tryptophan not only produces NAD but it also helps synthesize brain chemicals like serotonin, an important mood-stabilizing molecule.  Resveratrol also elevates serotonin levels.

    While typical intake of tryptophan for many individuals is approximately 900 to 1000 mg daily, the recommended daily allowance for adults is estimated to be between 250 mg/day and 1000+ mg/day.

    Melatonin, the sleep hormone produced in the pineal gland at the base of the brain, is also synthesized from tryptophan.

    In fact, the primary de novo (from the beginning) synthesis of NAD+ generally initiates from tryptophan.

    Given that tryptophan consumption may be therapeutic for sleeplessness, memory decline, mood, thinking, mood states like obsessive-compulsive disorder, PMS, panic disorder, depression, memory and recall, as well as NAD maintenance, maybe tryptophan should be the supplement of choice to boost NAD levels.

    The therapeutic use of tryptophan for treatment of clinical disorders and syndromes has concentrated primarily on increasing tryptophan intake for the treatment of depressive disorders and other related conditions.  Tryptophan has been found to be as effective as tricyclic antidepressant drugs.

    Of particular interest is the fact that the red wine molecule resveratrol has been shown to regulate an enzyme (indoleamine-2-3-dioxygenase or IDO), which controls tryptophan metabolism.   So all roads to longevity pass through NAD and all roads to NAD appear to be addressed by resveratrol.

    NAD is so critical it has a primary (tryptophan) and back-up (niacin) mechanism of synthesis.

    Nicotinamide put to the test

    A setback for nicotinamide (niacinamide) as a life-extending agent was a recent study that showed it improves the quality of life (reduced inflammation, improved metabolism) but did not prolong the survival of lab animals.   But that study isn’t the final word on the subject.

    Researchers were able to use both resveratrol and niacinamide simultaneously in lab animals, which produced positive and measurable health benefits.

    Published scientific reports regarding niacin-NAD and superlongevity have existed for a long time .

    I have also written that resveratrol promises to reverse aging by a more powerful mechanism that niacin-like drugs.

    Niacin derivatives like NMN are now reported boost endurance in elderly mice by up to 80%.  Saying NMN activates Sirtuin1, researchers say NMN along with a methylated form of resveratrol may be able to rescue loss of muscle mass in humans as they age.  The researchers also mention in passing the hydrogen sulfide gas had a similar effect.  Hydrogen sulfide is newly revealed as a Sirtuin1 gene activator.

    Garlic’s gas activates Sirtuin1

    Hydrogen sulfide gas boosts Sirtuin1 gene protein and promotes new blood vessel growth (angiogenesis or neovascularization) that is part of the wound healing response.  Hydrogen sulfide gas is naturally produced from fresh crushed allicin-rich garlic cloves or alkaline- buffered garlic pills.

    Resveratrol’s dichotomy

    A captivating biological aspect of resveratrol is that it has been shown to inhibit abnormal blood vessels at the back of the eyes that impair vision while simultaneously promoting new blood vessels in a damaged heart to produce needed collateral circulation.  This dichotomy is considered to be one of nature’s miracles.  It’s difficult to throw out resveratrol for niacin.  However, niacin is essential for life.

    This is a difficult subject to sort out.  I’ve mentioned in prior postings this is a very difficult subject to sort through.  Other longevity seekers have also had difficulty turning niacin science into practical health advice.

    A daily multivitamin with an ample amount of niacin or niacinamide and a modestly dosed resveratrol pill with other synergistic nutrients ought to do.   If affordable, the newer NR or NMN may be worth trying.  Whether they are superior to niacin and niacinamide awaits more definitive studies.  ©2018 Bill Sardi,

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