Animal vs. human studies

Although most of the benefits of NMN have been shown on animal models, several human studies showing promising results have recently been published, and other clinical trials are on the way.

Here are a few examples:

NMN

• 250mg of NMN increases NAD levels: https://pubmed.ncbi.nlm.nih.gov/35479740/
• 250mg of NMN improves sleep & physical performance: https://www.mdpi.com/2072-6643/14/4/755/htm
• NMN shows telomere increase in humans: https://pubmed.ncbi.nlm.nih.gov/34912838/
• 250mg of NMN improves muscle function: https://assets.researchsquare.com/files/rs-455083/v1_covered.pdf
• 250mg of NMN improves metabolism & muscle insulin sensitivity in prediabetic women: https://pubmed.ncbi.nlm.nih.gov/33888596/

Human trials: 

From a scientific perspective, there are currently no safety concerns as NMN has been shown to be safe and has demonstrated tremendous health benefits in 11 human studies published in 2021/22.

• Safety of NMN supplementation up to 1.25 g/day with no adverse effects https://rdcu.be/c4gpB
• Safety of NMN intake, pharmacokinetics and positive effect on blood glucose: https://www.jstage.jst.go.jp/article/endocrj/67/2/67_EJ19-0313/_pdf/-char/en
• NAD+levels are significantly increased / safety of NMN: https://www.frontiersin.org/articles/10.3389/fnut.2022.868640/full
• NMN increases insulin sensitivity in prediabetic women: https://pubmed.ncbi.nlm.nih.gov/33888596/
• NAD+ increase with supplementation: https://www.frontiersin.org/articles/10.3389/fragi.2022.851698/full
• Improved muscle strength and performance: https://www.researchsquare.com/article/rs-455083/v1
• NMN supplementation increases blood NAD concentrations and is safe and well tolerated when taken orally up to 900 mg NMN daily / improves physical performance: https://link.springer.com/article/10.1007/s11357-022-00705-1
• Improves aerobic capacity in amateur runners https://jissn.biomedcentral.com/articles/10.1186/s12970-021-00442-4
• Potential of NMN to prevent loss of physical capacity and improve fatigue in older adults https://www.mdpi.com/2072-6643/14/4/755.
• Meta-analysis - has a significant positive effect on patients with cardiovascular disease and dyslipidaemia https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-022-00653-9 

This is an excellent website that summarizes all studies done on NMN, including all human trials: https://www.nmn.com/topic

This study shows NMN reversing signs of ageing in post menopausal women, for example: https://www.nmn.com/news/nmn-reverses-aging-older-women

Booster

1. Grant, R. Resveratrol Increases Intracellular NAD+ Levels Through Up Regulation of the NAD+ Synthetic Enzyme Nicotinamide Mononucleotide Adenylyltransferase. Nat Prec (2010). https://doi.org/10.1038/npre.2010.4421.1
2. Moraes, D. S., Moreira, D. C., Andrade, J., & Santos, S. (2020). Sirtuins, brain and cognition: A review of resveratrol effects. IBRO reports, 9, 46–51. https://doi.org/10.1016/j.ibror.2020.06.004
3. McCormack, D., & McFadden, D. (2013). A review of pterostilbene antioxidant activity and disease modification. Oxidative medicine and cellular longevity, 2013, 575482. https://doi.org/10.1155/2013/575482
4. Hernández-Camacho, Juan D et al. Coenzyme Q10 Supplementation in Aging and Disease. Frontiers in Physiology. 2018; 9(44)https://doi.org/10.3389/fphys.2018.00044
5. Castro-Marrero, J., Sáez-Francàs, N., Segundo, M. J., Calvo, N., Faro, M., Aliste, L., Fernández de Sevilla, T., & Alegre, J. (2016). Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome - A randomised, controlled, double-blind trial. Clinical nutrition (Edinburgh, Scotland), 35(4), 826–834. https://doi.org/10.1016/j.clnu.2015.07.010
6. Escande C, Nin V, Price NL, Capellini V, Gomes AP, Barbosa MT, O'Neil L, White TA, Sinclair DA, Chini EN. Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes. 2013; 62:1084–93. https://doi.org/10.2337/db12-1139
7. Ogura Y, Kitada M, Xu J, Monno I, Koya D,. CD38 inhibition by apigenin ameliorates mitochondrial oxidative stress through restoration of the intracellular NAD+/NADH ratio and Sirt3 activity in renal tubular cells in diabetic rats. Aging (Albany NY). 2020; 12:11325-11336. https://doi.org/10.18632/aging.103410
8. Zhao, G., He, F., Wu, C., Li, P., Li, N., Deng, J., Zhu, G., Ren, W., & Peng, Y. (2018). Betaine in Inflammation: Mechanistic Aspects and Applications. Frontiers in immunology, 9, 1070. https://doi.org/10.3389/fimmu.2018.01070
9. Sun, W. P., Zhai, M. Z., Li, D., Zhou, Y., Chen, N. N., Guo, M., & Zhou, S. S. (2017). Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma betaine and choline levels. Clinical nutrition (Edinburgh, Scotland), 36(4), 1136–1142.https://doi.org/10.1016/j.clnu.2016.07.016

Stabiliser 

Here, a few clinical trials based on our chosen ingredients:

White Mulberry leaf extract: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321430/

Berberine: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107691/

Chromium picolinate:https://pubmed.ncbi.nlm.nih.gov/17109600/

1. Thondre et al, 2021. Mulberry leaf extract improves glycaemic response and insulinemic response to sucrose in healthy subjects: results of a randomised, double-blind, placebo-controlled study. Nutrition & Metabolism; 18:41.
2. Wang et al, 2018. Mulberry leaf extract reduces the glycemic indexes of four common dietary carbohydrates. Medicine (2018) 97:34.
3. Li et al., 2018. Safety evaluation of mulberry leaf extract: acute, subacute toxicity and genotoxicity studies. Regulatory Toxicology and Pharmacology; 95: 220-226.
4. Lown et al, 2017. Mulberry extract improves glucose tolerance and decreases insulin concentrations in normoglycaemic adults: results of a randomised double-blind placebo controlled study. PLOS ONE.
5. Liu et al, 2016. Prevention effects and possible molecular mechanism of mulberry leaf extract and its formulation on rats with insulin sensitivity. PLOS ONE.
6. Lown et al, 2016. Mulberry extracts Reducose® total blood glucose in normoglycaemic adults. Diabetes UK Annual Conference
7. 1. Birdsall T, Kelly G. Berberine: therapeutic potential of an alkaloid found in several medicinal plants. Alt Med Rev. 1997;2(2):94-103.
8. 5. Lee YS, Kim WS, Kim KH, et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes. 2006;55(8):2256-2264.
9. Xu Z, Feng W, Shen Q, Yu N, Yu K, Wang S, Chen Z, Shioda S, Guo Y. Rhizoma Coptidis and Berberine as a Natural Drug to Combat Aging and Aging-Related Diseases via Anti-Oxidation and AMPK Activation. Aging Dis. 2017 Dec 1;8(6):760-777. doi: 10.14336/AD.2016.0620. PMID: 29344415; PMCID: PMC5758350.
10. Brownley, K. A., Von Holle, A., Hamer, R. M., La Via, M., & Bulik, C. M. (2013). A double-blind, randomized pilot trial of chromium picolinate for binge eating disorder: results of the Binge Eating and Chromium (BEACh) study. Journal of psychosomatic research, 75(1), 36–42.
11. Pei D, Hsieh CH, Hung YJ, Li JC, Lee CH, Kuo SW. The influence of chromium chloride-containing milk to glycemic control of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Metabolism. 2006 Jul;55(7):923-7.