NAD+ is a coenzyme that cells use to move energy through their mitochondria, and enzymes that repair DNA and regulate metabolism also depend on it. A review in Nature Reviews Molecular Cell Biology describes NAD+ levels falling with age in several species, and argues that this fall contributes to the diseases of aging. That is why energy and NAD+ are sold together. The question for a patient is simpler: does raising NAD+ or its building blocks change how people feel or function? So far the honest answer is a little, in small trials, and not yet for injections.
Precursors: what the trials tested
Most human NAD+ trials have given the building blocks, not NAD+ itself. In a placebo-controlled trial, 250 mg a day of NMN for 10 weeks raised muscle insulin sensitivity in 25 postmenopausal women with prediabetes (13 on NMN, 12 on placebo). Blood glucose and blood pressure did not change, and the authors call for larger studies before any claim about prediabetes (Yoshino 2021).
In a 12-week trial in healthy older men, chronic NMN raised blood NAD+. The trial reported better gait speed and grip strength, but it was small and partly funded by the company that makes NMN (Igarashi 2022).
In a small crossover trial of nicotinamide riboside, 1,000 mg a day in two six-week periods in healthy middle-aged and older adults, blood NAD+ rose and no adverse effects were reported. The blood-pressure findings were preliminary (Martens 2018).
Injections: the thinnest part
IV NAD+ is the product people ask about most, and it has the thinnest evidence. We found no large controlled trial of IV NAD+ for fatigue or energy.
A 2026 retrospective pilot compared IV NAD+ with IV nicotinamide riboside at 500 mg a day for four days. The NAD+ infusions averaged 97 minutes against 37 minutes for nicotinamide riboside, because of gastrointestinal symptoms, a faster heart rate and chest pressure during the infusion. Liver and kidney markers did not change. The study measured tolerability, not energy.
Glutathione: stores, and what has not been shown
In a six-month, randomized, placebo-controlled trial of 54 non-smoking adults, oral glutathione at 250 or 1,000 mg a day raised glutathione stores in blood and cells. The trial measured body stores, not illness, energy or function, and the company that makes the ingredient supported it (Richie 2015).
A separate trial in older adults used GlyNAC, a combination of glycine and N-acetylcysteine, not glutathione itself. In a 16-week randomized trial of 24 older adults, GlyNAC was linked with faster gait speed (gains of about 19% were reported) and better markers of oxidative stress and inflammation than placebo (Sekhar 2023). The study is small, and it did not test glutathione injections.
Methylene blue: small studies of the brain
Methylene blue is being studied for its effect on brain energy use. In a randomized, placebo-controlled study of 26 healthy adults aged 22 to 62, a low dose increased brain activity on functional MRI during a sustained-attention task and a memory task (Radiology 2016).
That is a brain-imaging result in volunteers. It does not measure memory, mood or energy over time. Trials in Alzheimer’s disease exist, but we have not verified their final results, so we do not cite them here.
Where the evidence stands
The strongest human data is for NAD+ precursors and their effect on blood NAD+ and on muscle glucose handling, in trials of tens of people. For energy and daily function the data are early. For IV NAD+, glutathione injections and methylene blue, we have no trial showing that they improve how people feel over time.
What this does not say
- Most trials tested NMN or nicotinamide riboside, not NAD+ injections. Precursor results do not transfer to IV NAD+ or to the NAD+ we inject.
- The trials are small and short. Several were funded by companies that make the ingredient, and some findings are preliminary.
- A rise in blood NAD+ or glutathione is not the same as more energy, better function or a longer life. None of these trials measured lifespan.
- The trials used specific doses and products. Their results are averages for those groups, not predictions for one person, and compounded or differently sourced products were not studied.
How we use this
Our physicians do not present NAD+, glutathione or methylene blue as a cure for tiredness. When someone asks about them, we explain what the trials tested, at what dose, and where the evidence stops.
If a product is part of your plan, we say what the evidence is, what it is not, and how we will check whether it is helping.
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- 1.Covarrubias AJ et al. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22:119-141. Nature Reviews Molecular Cell Biology
- 2.Yoshino J et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021. Science
- 3.Igarashi M et al. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. npj Aging. 2022. npj Aging
- 4.Martens CR et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018. Nature Communications
- 5.Intravenous NAD+ versus nicotinamide riboside: a retrospective tolerability pilot study in a real-world setting. 2026. PubMed Central
- 6.Richie JP Jr et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. 2015;54:251-263. European Journal of Nutrition
- 7.Sekhar RV et al. Supplementing glycine and N-acetylcysteine (GlyNAC) in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, physical function, and aging hallmarks: a randomized clinical trial. J Gerontol A Biol Sci Med Sci. 2023. Journals of Gerontology, Series A
- 8.Multimodal randomized functional MR imaging of the effects of methylene blue in the human brain. Radiology. 2016. Radiology