Here’s what the scientific literature says about dosing NMN and Resveratrol.
There's a lot of confusion about dosage, and routes of administration out there, none of which is based on the actual clinical data. Some of this confusion originates from Dr. David Sinclair himself as people are misunderstanding what he's saying when he describes the hydrophobic nature of resveratrol powder (brick dust as he describes it). In past interviews, Dr. Sinclair has explained that he does have a lot of NMN and Resveratrol left over from various studies, so he will mix about a gram of each into a few spoonfuls of his homemade yogurt in the morning. This doesn't mean however that you need to take this much, and it doesn't mean that resveratrol needs to be mixed into fat before consumption, as it will all get mixed in digestion anyway; it's just what he does because he has a lot of powder lying around. Oral administration with fat is what matters most with resveratrol, not in fat.
Furthermore we are unable to find any human data with resveratrol where it was administered in a powdered form mixed in with fat. We align our formula, dosage, and mechanism of delivery as best we can with the publicly available science, not hearsay, pseudo-experts, or what's trending on podcasts and social media.
A small sample of the literature on Resveratrol in human studies, all of which use capsules, and have positive endpoints.
Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans - 150 mg/day resveratrol in a capsule
Pilot Study of Resveratrol in Older Adults With Impaired Glucose Tolerance - 1g, 1.5g, and 2 g/day, taken in divided doses in a capsule
Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients - 500 mg, twice a day in capsules
The Effect of Resveratrol Supplementation on Cardio-Metabolic Risk Factors in Patients with Type 2 Diabetes: A Randomized, Double-Blind Controlled Trial - 500 mg taken twice per day in capsules (micronized)
Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: A randomized controlled trial - 300 mg taken twice per day in capsules
Effects of Resveratrol on Memory Performance, Hippocampal Functional Connectivity, and Glucose Metabolism in Healthy Older Adults - 200 mg of resveratrol /day in capsules
VERSO Cell Being uses to micronized resveratrol, which does have some evidence suggesting that it increases absorption over standard resveratrol powder, as particle size reduction is believed to enhance the bioavailability of resveratrol primarily due to the increase in surface area and improved suspension properties:
Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases—Safety, pharmacokinetics, and pharmacodynamics - A human trial - Micronized resveratrol increases absorption by 3.6 fold over standard resveratrol powder - interesting to note that the micronized resveratrol was delivered in a distilled water solution (with a few additives: docusate sodium, citric acid, colorant, glycerin, flavoring, sodium citrate, sodium saccharin, and sorbitol).
NMN has been the subject of a lot speculation regarding dosage, and routes of administration (gut breakdown models, liposomal, sublingual, and other speculative nonsense or marketing hype), but the clinical data in human studies so far hasn't proven any of these alternative routes of administration, it is given orally in capsules/tablets/powder and shown to raise NAD+ levels:
Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide (NAD+) Levels in Healthy Subjects - Tablets containing 125 mg of NMN were given twice a day (250mg/day). NAD+ levels in whole blood were significantly increased after NMN administration. These results suggest that oral administration of NMN is a safe and practical strategy to boost NAD+ levels in humans.
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women - 250mg/day in capsules. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese.
Human safety trial on NMN: Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men - 100mg, 250mg, or 500mg doses were given, in capsules. The single oral administration of NMN up to 500 mg was safe and well-tolerated in healthy men without causing any significant deleterious effects. Thus, oral administration of NMN is feasible and could be a therapeutic strategy to replenish cellular NAD+ levels to mitigate aging-related functional disorders in humans. Interesting to note the downstream metabolites of NMN were raised in all dosages, suggesting bioavailability, and a dose-dependent response. This study was the first human data to be made public.
Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men - Oral administration of 250mg/day (capsule/tablet not specified). These results showed an elevation in blood NAD+ levels and saw improvements in motor function.
Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study - oral supplementation of NMN powder of 300mg, 600mg, or 1200mg per day. NMN increases the aerobic capacity of humans during exercise training, and the improvement is likely the result of enhanced O2 utilization of the skeletal muscle.
In certain rodent models they even mix NMN into the drinking water, Dr. Sinclair has talked about this on numerous occasions when discussing the stability of NMN, and that it's only stable for about a week in water, as an example:
Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice - To make long-term NMN administration possible, they decided to test lower doses, which could potentially be translatable to humans, and add it to drinking water. They also confirmed that 93%–99% of NMN was maintained intact in drinking water at room temperature for 7–10 days.
Most of the research on TMG (Betaine) is focused around endpoints like targeting homocysteine levels, body composition, athletic performance, metabolism, and more. At this moment there are no studies that specifically look at TMG with NMN through the lends of a methyl donor NAD+ synthesis. However TMG is a safe and effective option to improve methylation pathways and add methyl donors, to potentially avoid depleting methyl groups from NAD+ synthesis. David Sinclair has mentioned that he personally takes TMG, along with NMN and Resveratrol.
A small sample of the literature around dosage and TMG in human studies:
Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis: Supplementation with betaine at a dosage of at least 4 grams/day for at least 6 weeks can lower plasma homocysteine by 5% to 20%.
Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects: Betaine supplementation at 6 grams/day for 12 weeks, combined with a hypoenergetic diet reduced plasma homocysteine concentration for obese participants.
Ergogenic effects of betaine supplementation on strength and power performance: A betaine supplement with a dosage of 1.25 grams combined with 300 mL of Gatorade© sports drink, taken twice daily, led to increases in power, force and maintenance across certain performance measures.
Effect of betaine supplementation on power performance and fatigue: Betaine supplementation with a dosage of 1.25 grams combined with 240 ml of a sports drink, twice daily for two-weeks led to improvements in muscle endurance for squats.
The effects of chronic betaine supplementation on body composition and performance in collegiate females: a double-blind, randomized, placebo controlled trial: Betaine supplementation at 2.5 g/day for 8 weeks, may enhance fat mass reductions for untrained collegiate females.
Effect of Betaine on Reducing Body Fat—A Systematic Review and Meta-Analysis of Randomized Controlled Trials: Various dosages and time frames (see below). Betaine supplementation significantly reduced the total body fat mass and body fat percentage. No changes were observed regarding body weight and body mass index. The results suggested that dietary betaine supplementation might be an effective approach for reducing body fat.
Broadly speaking, supplements fall into two categories, fat soluble and water soluble. NMN is water soluble, and Resveratrol is fat soluble. There are many fat-soluble supplements out there (like vitamins A, D, E, and K), and all of which will state that they should be taken with food, not mixed with fat before consumption (not that it would matter either way). Water soluble supplements on the other hand are not required to be taken with fat for absorption, but are not harmed by being taken with a meal (or fats).