Nicotinamide riboside supplementation to improve skeletal muscle mitochondrial health and whole‐body glucose homeostasis: does it actually work in humans?

Leduc‐Gaudet, Jean‐Philippe; Dulac, Maude; Reynaud, Olivier; Ayoub, Marie-Belle; Gouspillou, Gilles

doi:10.1113/jp279280

Cited by 8 publications

(6 citation statements)

References 6 publications

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“…Hence, it, like AMPK activators, has potential to enhance the availability Sirt1’s substrate NAD+ 107 108. Unfortunately, clinical supplementation studies involving NR intakes of up to 2 g daily have failed to show an impact of such supplementation on skeletal muscle NAD+ levels or indices of mitochondrial function; nor has NR supplementation so far shown an impact on insulin sensitivity in obese, insulin-resistant men 109. However, an increase of NAD+ in blood mononuclear cells has been reported in subjects receiving long-term NR supplementation at 500 mg two times a day 110.…”

Section: Ancillary Nutraceuticals May Amplify the Beneficial Impacts ...mentioning

confidence: 99%

Ferulic acid and berberine, via Sirt1 and AMPK, may act as cell cleansing promoters of healthy longevity

et al. 2022

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Ferulic acid, a bacterial metabolite of anthocyanins, seems likely to be a primary mediator of the health benefits associated with anthocyanin-rich diets, and has long been employed in Chinese cardiovascular medicine. In rodent studies, it has exerted wide-ranging antioxidant and anti-inflammatory effects, the molecular basis of which remains rather obscure. However, recent studies indicate that physiologically relevant concentrations of ferulic acid can boost expression of Sirt1 at mRNA and protein levels in a range of tissues. Sirt1, a class III deacetylase, functions to detect a paucity of oxidisable substrate, and in response works in various ways to promote cellular survival and healthful longevity. Sirt1 promotes ‘cell cleansing’ and cell survival by boosting autophagy, mitophagy, mitochondrial biogenesis, phase 2 induction of antioxidant enzymes via Nrf2, and DNA repair—while inhibiting NF-kB-driven inflammation, apoptosis, and cellular senescence, and boosting endothelial expression of the protective transcription factor kruppel-like factor 2. A deficit of the latter appears to mediate the endothelial toxicity of the SARS-CoV-2 spike protein. Ferulic acid also enhances the activation of AMP-activated kinase (AMPK) by increasing expression and activity of its activating kinase LKB1—whereas AMPK in turn amplifies Sirt1 activity by promoting induction of nicotinamide phosphoribosyltranferase, rate-limiting for generation of Sirt1’s obligate substrate NAD+. Curiously, AMPK acts by independent mechanisms to potentiate many of the effects mediated by Sirt1. Hence, it is proposed that ferulic acid may exert complementary or synergistic health-promoting effects when used in conjunction with clinically useful AMPK activators, such as the nutraceutical berberine. Additional nutraceuticals which might have potential for amplifying certain protective effects of ferulic acid/berberine are also discussed.

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Section: Ancillary Nutraceuticals May Amplify the Beneficial Impacts ...mentioning

confidence: 99%

Ferulic acid and berberine, via Sirt1 and AMPK, may act as cell cleansing promoters of healthy longevity

et al. 2022

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“…De novo synthesis of NAD+ can be enhanced by precursors such as nicotinamide riboside or nicotinamide mononucleoside, each of which are Sirt1 activators. [84][85][86][87][88][89] AMP-activated protein kinase (AMPK) boosts NAD+ synthesis via induction of the enzyme nicotinamide ribosylphosphotransferase (NAMPT), rate limiting for conversion of nicotinamide to NAD+. [90][91][92] Since nicotinamide is a product of Sirt1 activity that inhibits Sirt1, NAMPT also promotes Sirt1 activity by alleviating this inhibition.…”

Section: Health Promotion Via Sirtuin 1 Activationmentioning

confidence: 99%

Nutraceutical activation of Sirt1: a review

2022

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The deacetylase sirtuin 1 (Sirt1), activated by calorie restriction and fasting, exerts several complementary effects on cellular function that are favourable to healthspan; it is often thought of as an ‘anti-aging’ enzyme. Practical measures which might boost Sirt1 activity are therefore of considerable interest. A number of nutraceuticals have potential in this regard. Nutraceuticals reported to enhance Sirt1 synthesis or protein expression include ferulic acid, tetrahydrocurcumin, urolithin A, melatonin, astaxanthin, carnosic acid and neochlorogenic acid. The half-life of Sirt1 protein can be enhanced with the natural nicotinamide catabolite N1-methylnicotinamide. The availability of Sirt1’s obligate substrate NAD+ can be increased in several ways: nicotinamide riboside and nicotinamide mononucleotide can function as substrates for NAD+ synthesis; activators of AMP-activated kinase—such as berberine—can increase expression of nicotinamide phosphoribosyltransferase, which is rate limiting for NAD+ synthesis; and nutraceutical quinones such as thymoquinone and pyrroloquinoline quinone can boost NAD+ by promoting oxidation of NADH. Induced ketosis—as via ingestion of medium-chain triglycerides—can increase NAD+ in the brain by lessening the reduction of NAD+ mediated by glycolysis. Post-translational modifications of Sirt1 by O-GlcNAcylation or sulfonation can increase its activity, suggesting that administration of glucosamine or of agents promoting hydrogen sulfide synthesis may aid Sirt1 activity. Although resveratrol has poor pharmacokinetics, it can bind to Sirt1 and activate it allosterically—as can so-called sirtuin-activating compound drugs. Since oxidative stress can reduce Sirt1 activity in multiple ways, effective antioxidant supplementation that blunts such stress may also help preserve Sirt1 activity in some circumstances. Combination nutraceutical regimens providing physiologically meaningful doses of several of these agents, capable of activating Sirt1 in complementary ways, may have considerable potential for health promotion. Such measures may also amplify the benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors in non-diabetic disorders, as these benefits appear to reflect upregulation of Sirt1 and AMP-activated protein kinase activities.

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“…Overall, these data do not support the hypothesis that dietary NR supplementation has a significant impact on skeletal muscle mitochondria in obese and insulin-resistant men. This could at least partly be explained by the fact that, despite having elevated urine levels of NAD+-derived metabolites, the tissue content of NAD+, NADH, NADP+, or NADPH in the skeletal muscle in men receiving NR did not differ from those receiving placebos ( 35 , 36 ).…”

Section: Results Of Therapeutic Interventions With Different Forms Of...mentioning

confidence: 98%

NAD+-Increasing Strategies to Improve Cardiometabolic Health?

et al. 2022

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Depleted nicotinamide adenine dinucleotide (NAD+) is a common hallmark of metabolic disorders. Therefore, NAD+-increasing strategies have evolved as a potential therapeutic venue to combat cardiometabolic diseases. Several forms of vitamin B3, i.e., nicotinamide and nicotinamide mononucleotide, and especially nicotinamide riboside, have attracted most interest as potentially safe and efficacious candidates for NAD+ restoration. Herein, we dissected the characteristics of the latest clinical trials testing the therapeutic potential of different vitamin B3 molecules to improve cardiometabolic health, with a special focus on randomized, placebo-controlled clinical trials performed in the context of obesity or other pathologies, mainly linked to cardiovascular system and skeletal muscle functionality. The favorable outcomes via NAD+-increasing strategies found in the different studies were quite heterogeneous. NAD+-increasing interventions improved capacity to exercise, decreased blood pressure, increased the anti-inflammatory profile and insulin-stimulated glucose disposal, and reduced the fat-free mass. Except for the decreased blood pressure, the significant results did not include many hard clinical end points, such as decreases in weight, BMI, fasting glucose, or HbA1c percentage. However, the analyzed trials were short-term interventions. Overall, the accumulated clinical data can be interpreted as moderately promising. Additional and long-term studies will be needed to directly compare the doses and duration of treatments among different vitamin B3 regimes, as well as to define the type of patients, if any, that could benefit from these treatments. In this context, a major point of advancement in delineating future clinical trials would be to identify subjects with a recognized NAD+ deficiency using novel, appropriate biomarkers. Also, confirmation of gender-specific effect of NAD+-increasing treatments would be needed.

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Nicotinamide riboside supplementation to improve skeletal muscle mitochondrial health and whole‐body glucose homeostasis: does it actually work in humans?

Cited by 8 publications

References 6 publications

Ferulic acid and berberine, via Sirt1 and AMPK, may act as cell cleansing promoters of healthy longevity

Ferulic acid and berberine, via Sirt1 and AMPK, may act as cell cleansing promoters of healthy longevity

Nutraceutical activation of Sirt1: a review

NAD+-Increasing Strategies to Improve Cardiometabolic Health?

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