Research Studies on NAD+ and Resveratrol

NAD+ and Aging (DNA Repair, Longevity, Mitochondrial Health)

• A conserved NAD+ binding pocket that regulates protein-protein interactions during aging (2017) – Science: Identified that declining NAD+ levels with age lead to impaired DNA repair; restoring NAD+ in older mice disrupted a harmful protein interaction (PARP1-DBC1), thereby rapidly reversing age-related DNA damage accumulationpubmed.ncbi.nlm.nih.gov. This suggests NAD+ replenishment may protect against aging and genomic instability.

• Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice (2016) – Cell Metabolism: In a 12-month study, oral NMN (an NAD+ precursor) in normal aging mice effectively countered age-related decline. Treated mice showed preserved body weight, enhanced energy metabolism, increased physical activity, improved insulin sensitivity, better lipid profiles, and improved eye function without toxicity pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov. The findings highlight NAD+ intermediates’ potential as anti-aging interventions in mammals.

• Chronic Nicotinamide Riboside Supplementation is Well-Tolerated and Elevates NAD+ in Healthy Middle-Aged and Older Adults (2018) – Nature Communications: Six-week NR supplementation (500 mg twice daily) in adults (55–79 y) safely raised blood NAD+ levels ~60%. Exploratory outcomes suggested NR may reduce systolic blood pressure and arterial stiffness in older individuals (especially those with elevated baseline BP), pointing to cardiovascular anti-aging benefits nature.com. (Martens et al., 2018)

NAD+ and Energy Production (Cellular Metabolism, ATP, Fatigue)

• Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women (2021) – Science: In a 10-week double-blind trial, postmenopausal women with prediabetes received NMN (250 mg/day) or placebo. NMN significantly improved skeletal muscle insulin sensitivity and enhanced insulin signaling pathways pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov. It also upregulated genes for muscle remodeling, indicating better cellular energy utilization. This human study demonstrates that boosting NAD+ can improve metabolic energy production and glucose handling.

• Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome (1999) – Annals of Allergy, Asthma & Immunology: In a randomized crossover trial, 26 CFS patients took NADH (10 mg daily) or placebo for 4 weeks. 31% of patients responded positively to NADH vs 8% on placebo, with no severe side effects pubmed.ncbi.nlm.nih.gov. NADH (the reduced form of NAD+) is known to drive ATP generation, and responders saw improvements in fatigue and cognitive symptoms. This pilot suggests NADH may help alleviate chronic fatigue by supporting cellular ATP production.

NAD+ and Cognitive Function (Mental Clarity, Focus, Neuroprotection)

• Nicotinamide mononucleotide (NMN) supplementation…improves cognitive function in aged mice (2019) – Redox Biology: A short-term NMN treatment in old mice restored neurovascular coupling (blood flow responses in the brain) and mitochondrial function. Treated aged mice showed significant improvements in learning and memory performance (e.g. better maze test results) compared to untreated aged controls nmn.com. The NMN-mediated boost in brain blood flow and energy metabolism translated to enhanced cognitive function in the aging mice nmn.com, highlighting NMN’s neuroprotective potential.

• Effects of Resveratrol on Memory Performance, Hippocampal Functional Connectivity, and Glucose Metabolism in Healthy Older Adults (2014) – Journal of Neuroscience: In a 26-week placebo-controlled trial, 46 overweight elders (50–75 y) took 200 mg/day resveratrol or placebo. The resveratrol group showed significantly better word retention (memory) after 30 minutes than placebo (p = 0.038) pubmed.ncbi.nlm.nih.gov. They also exhibited increased hippocampal functional connectivity and lowered HbA1c (improved glucose metabolism) pubmed.ncbi.nlm.nih.gov. This provides initial evidence that resveratrol supplementation can improve memory performance and brain connectivity in older adults.

• Resveratrol Prevents Age-Related Memory and Mood Dysfunction… (2015) – Scientific Reports: Late middle-aged rats given resveratrol for 4 weeks outperformed controls in learning, memory, and mood tests at ~25 months old nature.com. Resveratrol-treated rats had increased hippocampal neurogenesis and microvasculature and reduced neuroinflammation (less activated glia) nature.com. The study demonstrates resveratrol’s neuroprotective effect, indicating it can preserve cognitive function and elevate mood in aging by promoting brain plasticity and reducing inflammation.

NAD+ and Skin Health (Appearance, Collagen, Anti-Aging Effects)

• A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention (2015) – New England Journal of Medicine: In a one-year trial with 386 high-risk patients, oral nicotinamide (vitamin B3, 500 mg twice daily) reduced new non-melanoma skin cancers by 23% vs placebo (p=0.02) pubmed.ncbi.nlm.nih.gov. It also significantly lowered the number of precancerous actinic keratoses at 3, 6, 9, and 12 months. Nicotinamide (which boosts NAD+ levels in cells) likely enhanced DNA repair of UV damage nejm.org, improving skin cell health. This evidence shows NAD+ augmentation can protect skin integrity and reduce UV-driven skin aging/cancer.

• Skin Anti-Aging Benefits of a 2% Resveratrol Emulsion (2021) – J. of Cosmetics, Derm. Sci. & Apps.: A clinical study of 20 subjects applying a 2% resveratrol cream daily for 8 weeks found notable improvements in skin properties. Skin elasticity increased by ~5%, density by ~11%, while roughness decreased ~6% scirp.org. Participants and dermatologists reported reduced wrinkles, firmer skin and less redness scirp.org. These results indicate topical resveratrol can enhance collagen production, improve skin firmness and smoothness, supporting its anti-aging effects on skin appearance.

NAD+ and Inflammation / Pain Relief

• The effect of niacinamide on osteoarthritis: a pilot study (1996) – Inflammation Research: A double-blind trial in 72 patients with osteoarthritis showed that high-dose niacinamide (vitamin B3, 3 g/day divided) led to a 29% improvement in global arthritis scores (versus a 10% worsening in placebo group) over 12 weeks pubmed.ncbi.nlm.nih.gov. Niacinamide (which raises NAD+ levels) also reduced inflammation markers (ESR down 22%) and increased joint mobility, allowing some patients to decrease standard anti-inflammatory medications pubmed.ncbi.nlm.nih.gov. This suggests NAD+ enhancement has anti-inflammatory effects that can alleviate arthritis pain and improve joint function.

• Resveratrol Supplementation Reduces Pain and Inflammation in Knee Osteoarthritis (2018) – Journal of Medicinal Food: In a placebo-controlled study, 110 adults with knee OA were given 500 mg/day resveratrol or placebo as an adjunct to meloxicam (an NSAID) for 90 days. The resveratrol group experienced a gradual, significant decrease in knee pain severity compared to placebo caringmedical.com. Inflammatory biomarkers (like TNF-α and IL-6) were also reduced. This RCT concluded that adding resveratrol (a natural SIRT1 activator and polyphenol) can amplify anti-inflammatory and analgesic effects, improving outcomes in osteoarthritis patients.

Synergistic Effects of NAD+ and Resveratrol

• Improvement of NAD+ levels with Combined NMN and Resveratrol (2022) – Pharmacol. Research & Perspectives: This mouse study tested nicotinamide mononucleotide (NMN) with or without resveratrol. Combining NMN (500 mg/kg) with resveratrol (50 mg/kg) led to significantly higher NAD+ increases in tissues than NMN alone – about 1.6× higher NAD+ in the heart and 1.7× in skeletal muscle pubmed.ncbi.nlm.nih.gov. Such synergistic boosting of NAD+ in muscle and cardiac tissue suggests that resveratrol can enhance the tissue availability of NAD+, potentially improving energy metabolism and endurance when used together.

• Repeat Dose NRPT Increases NAD+ Levels in Humans (2017) – NPJ Aging and Mechanisms of Disease: NRPT is a combination of nicotinamide riboside (NR, an NAD+ precursor) and pterostilbene (a methylated form of resveratrol). In a randomized trial with 120 adults (60–80 y), 8 weeks of NRPT raised whole-blood NAD+ by ~40% at the standard dose (250 mg NR + 50 mg pterostilbene) and ~90% at double dose pubmed.ncbi.nlm.nih.gov. NAD+ remained elevated throughout the study with no serious adverse effects. This illustrates in humans that NAD+ precursors plus a sirtuin-activating polyphenol can safely and effectively elevate NAD+, supporting the combined use of NAD+ boosters and resveratrol-like compounds for synergistic health benefits.