Recently, the interim report of Japan’s NMN clinical trial showed positive results, marking the first clinical confirmation of the effects of oral NMN in humans. This initial success of the "anti-aging miracle drug" has garnered significant attention. As someone at the forefront of NMN science popularization, unlike those who are either eager to try it or full of doubts, this author has even started worrying about never being able to retire. 😳😳
If I had to set a time limit for my work, I wish it were 10,000 years.
Is NMN really a "magic pill" for anti-aging? What exactly makes it "miraculous"? To answer these questions, I can explain NMN’s specific effects from two perspectives: subjective user experiences and clinical experiments. 😎😎
First: Non-Clinical Feedback from Users
It has been nearly two years since NMN products were launched in Japan, the United States, and China, accumulating tens of thousands of users. According to feedback, 80% of users reported noticeable improvements in bodily functions after oral NMN intake. However, effects vary by individual, including:
| User Feedback on NMN Intake | ||
|---|---|---|
| 1. Lowered blood sugar, increased insulin sensitivity | 2. Regulated circadian rhythm, improved sleep, relieved jet lag | 3. Improved cardiovascular function |
| 4. Enhanced energy levels | 5. Reduced blood lipids, improved LDL/HDL ratio | 6. Boosted immune function |
| 7. Skin rejuvenation, stopped hair loss, promoted new hair growth, reversed gray hair to black | 8. Alleviated chemotherapy side effects | 9. Increased basal metabolism, reduced fat formation, converted fat to muscle, promoted muscle regeneration |
| 10. Improved/relieved Alzheimer’s symptoms | 11. Regulated blood pressure | 12. Reduced/eliminated depression |
| 13. Enhanced exercise capacity, improved marathon performance | 14. Improved/eliminated constipation | 15. Accelerated alcohol metabolism, increased alcohol tolerance, relieved hangover |
| 16. Boosted male hormones, improved sexual function | 17. Enhanced memory, improved hearing | 18. Reduced/eliminated altitude sickness |
| 19. Eliminated motion sickness | 20. Reduced/eliminated food allergies | 21. Strengthened microvascular function, promoted regrowth of atrophied gums |
| 22. Alleviated inflammation | 23. Reduced fatty liver | 24. Increased appetite |
| 25. Improved myopia | 26. Regularized menstrual cycles |
Note: Feedback is collected from online sources. Each item listed has several to dozens of reports, including subjective experiences and medical examination results. The above data have not undergone systematic and rigorous statistical processing.
NMN seems to improve so many functions—it’s almost like a "cure-all." Is this possible?
In fact, once you understand NMN’s mechanism of action, its powerful effects become less surprising: 😯😯
As mentioned in our previous article, aging is largely caused by the deficiency of coenzyme I (NAD+) in the human body. After entering middle and old age, NAD+ levels drop sharply, triggering various aging symptoms. NMN is rapidly converted into NAD+ in the body, restoring NAD+ to youthful levels and re-establishing normal physiological functions (regulating hundreds of metabolic reactions, maintaining longevity protein activity, repairing DNA, sustaining immune system function, etc.). This reverses aging at its source and root. 😎😎
Second: Animal Clinical Trial Results from International Literature
If the above are just user experiences, I have also compiled results from animal experiments in international literature. Whether administered as a single dose or long-term (up to 12 months), orally or via injection, NMN showed positive effects in various animal models (sorted by time):
Animal Clinical Trials of NMN
| Animal Model | Dose | Administration Duration | Results | Reference |
|---|---|---|---|---|
| Nampt heterozygous KO mice | 500 mg/kg (IP) | Single dose | Improved glucose tolerance and insulin secretion | Revollo et al., 2007[1] |
| Age-induced diabetic mice | 500 mg/kg (IP) | 11 days | Improved insulin sensitivity and plasma lipid profile | Yoshino et al., 2011[2] |
| Mice fed a high-sugar diet | 500 mg/kg (IP) | Single dose | Enhanced insulin secretion, inhibited inflammation | Caton et al., 2011[3] |
| C57BL/6J mice | 500 mg/kg (IP) | 7 days | Enhanced mitochondrial oxidative metabolism in skeletal muscle of aged mice | Gomes et al., 2013[4] |
| Bmal1 KO mice | 500 mg/kg (IP) | 10 days | Increased hepatic mitochondrial respiration | Peek et al., 2013[5] |
| Mice with heart-specific Ndufs4 KD | 500 mg/kg (IP) | 3 days | Reduced mitochondrial protein acetylation, improved mitochondrial permeability transition pore (mPTP) sensitivity | Karamanlidis et al., 2013[6] |
| Mice injected with miR-34a-overexpressing adenoviral vector | 500 mg/kg (IP) | 10 days | Improved glucose tolerance, increased expression of fatty acid β-oxidation genes | Choi et al., 2013[7] |
| C57BL/6N mice | 100–300 mg/kg (in drinking water) | 12 months | Maintained neural stem cell pool, inhibited age-induced weight gain, improved insulin sensitivity and blood lipids, increased physical activity, energy expenditure, and muscle mitochondrial function | Stein and Imai, 2014[8] |
| C57BL/6T mice with ischemia/reperfusion-induced heart injury | 500 mg/kg (IP) | 1–4 doses | Reduced myocardial infarction area after ischemia/reperfusion | Yamamoto et al., 2014[9] |
| Alzheimer’s disease-related (AD Tg) mice | 100 mg/kg (SC) | 28 days (every other day) | Reduced amyloid precursor protein (APP) levels, enhanced mitochondrial function | Long et al., 2015[10] |
| Adipocyte-specific ANKD mice | 500 mg/kg (IP) | Single dose | Restored exercise capacity | Yoon et al., 2015[11] |
| C57BL/6 mice with cerebral ischemia | 31.25–500 mg/kg (IP) | Single dose | Reduced neuronal cell death, improved neurological outcomes | Park et al., 2016[12] |
| C57BL/6 mice | 300 mg/kg (in drinking water) | 8 weeks | Improved carotid artery endothelium-dependent dilation | de Picciotto et al., 2016[13] |
| Mice with adipocyte-specific Nampt KD and photoinduced retinal dysfunction | 150 mg/kg (IP) | 4 weeks | Improved retinal degeneration, protected retina from photoinduced damage | Lin et al., 2016[14] |
| Adipocyte-specific Nampt KD mice | 500 mg/kg (in drinking water) | 6–8 weeks | Improved multi-organ insulin sensitivity, increased adiponectin production, reduced free fatty acid production | Stromsdorfer et al., 2016[15] |
| Mice with transverse aortic constriction (TAC)-induced stress | 500 mg/kg (IP) | 33 days | Improved mitochondrial function, protected mice from heart failure | Lee et al., 2016[16] |
| Wistar rats (Alzheimer’s disease model) | 500 mg/kg (IP) | 10 days | Enhanced learning ability and memory | Wang et al., 2016[17] |
| APPswe/PS1d9 transgenic mice (Alzheimer’s disease model) | 100 mg/kg (SC) | 28 days | Improved cognitive function | Yao et al., 2017[18] |
| CD1 mice with collagen-induced intracerebral hemorrhage | 300 mg/kg (IP) | Single dose/7 days | Reduced cerebral edema and cell death (single dose); promoted recovery of body weight and neurological function (7 days) | Wei et al., 2017a[19] |
| Aged C57BL/6J mice; irradiated C57BL/6T mice | 500 mg/kg (IP); 2000 mg/kg (PO) | 7 days/8 days | Reduced DNA damage, prevented radiation-induced changes in white blood cells, lymphocytes, and hemoglobin | Li et al., 2017[20] |
| CD1 mice with cerebral ischemia treated with tissue plasminogen activator | 300 mg/kg (IP) | Single dose | Improved mortality rate, reduced cerebral infarction and edema, inhibited apoptosis and hemorrhage, preserved blood-brain barrier integrity | Wei et al., 2017b[21] |
Note: IP = Intraperitoneal Injection; SC = Subcutaneous Injection; PO = Oral Administration
With so many literature references and effects listed, I wonder if everyone’s eyes are getting tired from all this information? 🙈🙈
Beyond enhancing learning ability, improving memory, protecting eyesight, reducing radiation damage, and boosting endurance, what people care most about is NMN’s potential in improving diabetes, cardiovascular diseases, and neurodegenerative diseases.
These three age-related diseases can be described as "killers of the elderly." The first two need no further explanation, but Alzheimer’s and Parkinson’s disease are probably the most terrifying age-related diseases 😨😨—with weak onset symptoms, unclear pathological mechanisms, and poor efficacy of drug treatment. Countless people have been affected by these diseases without knowing why.
NMN’s performance in this regard is quite impressive. ✌✌ The results from these animal experiments are consistent with the feedback from human NMN users, mutually corroborating each other.
How exactly does NMN work in these diseases? We will explain this in the next part.
References (Swipe Up to View)
[1] Revollo, J.R., Korner, A., Mills, K.F., Satoh, A., Wang, T., Garten, A., Dasgupta, B., Sasaki, Y., Wolberger, C., Townsend, R.R., et al. (2007). Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab. 6, 363–375.
[2] Yoshino, J., Mills, K.F., Yoon, M.J., and Imai, S. (2011). Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 14, 528–536.
[3] Caton, P.W., Kieswich, J., Yaqoob, M.M., Holness, M.J., and Sugden, M.C. (2011). Nicotinamide mononucleotide protects against pro-inflammatory cytokine-mediated impairment of mouse islet function. Diabetologia 54, 3083–3092.
[4] Gomes, A.P., Price, N.L., Ling, A.J., Moslehi, J.J., Montgomery, M.K., Rajman, L., White, J.P., Teodoro, J.S., Wrann, C.D., Hubbard, B.P., et al. (2013). Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155, 1624–1638.
[5] Peek, C.B., Affinati, A.H., Ramsey, K.M., Kuo, H.Y., Yu, W., Sena, L.A., Ilkayeva, O., Marcheva, B., Kobayashi, Y., Omura, C., et al. (2013). Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342, 1243417.
[6] Karamanlidis, G., Lee, C.F., Garcia-Menendez, L., Kolwicz, S.C., Jr., Suthammarak, W., Gong, G., Sedensky, M.M., Morgan, P.G., Wang, W., and Tian, R. (2013). Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure. Cell Metab. 18, 239–250.
[7] Choi, S.E., Fu, T., Seok, S., Kim, D.H., Yu, E., Lee, K.W., Kang, Y., Li, X., Kemper, B., and Kemper, J.K. (2013). Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT. Aging Cell 12, 1062–1072.
[8] Stein, L.R., and Imai, S. (2014). Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging. EMBO J. 33, 1321–1340.
[9] Yamamoto, T., Byun, J., Zhai, P., Ikeda, Y., Oka, S., and Sadoshima, J. (2014). Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion. PLoS One 9, e98972.
[10] Long, A.N., Owens, K., Schlappal, A.E., Kristian, T., Fishman, P.S., and Schuh, R.A. (2015). Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer’s disease-relevant murine model. BMC Neurol. 15, 19.
[11] Yoon, M.J., Yoshida, M., Johnson, S., Takikawa, A., Usui, I., Tobe, K., Nakagawa, T., Yoshino, J., and Imai, S. (2015). SIRT1-mediated eNAMPT secretion from adipose tissue regulates hypothalamic NAD(+) and function in mice. Cell Metab. 21, 706–717.
[12] Park, J.H., Long, A., Owens, K., and Kristian, T. (2016). Nicotinamide mononucleotide inhibits post-ischemic NAD(+) degradation and dramatically ameliorates brain damage following global cerebral ischemia. Neurobiol. Dis. 95, 102–110.
[13] de Picciotto, N.E., Gano, L.B., Johnson, L.C., Martens, C.R., Sindler, A.L., Mills, K.F., Imai, S., and Seals, D.R. (2016). Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell 15, 522–530.
[14] Lin, J.B., Kubota, S., Ban, N., Yoshida, M., Santeford, A., Sene, A., Nakamura, R., Zapata, N., Kubota, M., Tsubota, K., et al. (2016). NAMPT-mediated NAD(+) biosynthesis is essential for vision in mice. Cell Rep. 17, 69–85.
[15] Stromsdorfer, K.L., Yamaguchi, S., Yoon, M.J., Moseley, A.C., Franczyk, M.P., Kelly, S.C., Qi, N., Imai, S., and Yoshino, J. (2016). NAMPT-mediated NAD(+) biosynthesis in adipocytes regulates adipose tissue function and multi-organ insulin sensitivity in mice. Cell Rep. 16, 1851–1860.
[16] Lee, C.F., Chavez, J.D., Garcia-Menendez, L., Choi, Y., Roe, N.D., Chiao, Y.A., Edgar, J.S., Goo, Y.A., Goodlett, D.R., Bruce, J.E., et al. (2016). Normalization of NAD+ redox balance as a therapy for heart failure. Circulation 134, 883–894.
[17] Wang, X., Hu, X., Yang, Y., Takata, T., and Sakurai, T. (2016). Nicotinamide mononucleotide protects against beta-amyloid oligomer-induced cognitive impairment and neuronal death. Brain Res. 1643, 1–9.
[18] Yao, Z., Yang, W., Gao, Z., and Jia, P. (2017). Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease. Neurosci. Lett. 647, 133–140.
[19] Wei, C.C., Kong, Y.Y., Li, G.Q., Guan, Y.F., Wang, P., and Miao, C.Y. (2017a). Nicotinamide mononucleotide attenuates brain injury after intracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway. Sci. Rep. 7, 717.
[20] Li, J., Bonkowski, M.S., Moniot, S., Zhang, D., Hubbard, B.P., Ling, A.J., Rajman, L.A., Qin, B., Lou, Z., Gorbunova, V., et al. (2017). A conserved NAD+ binding pocket that regulates protein-protein interactions during aging. Science 355, 1312–1317.
[21] Wei, C.C., Kong, Y.Y., Xia, H., Li, G.Q., Zheng, S.L., Cheng, M.H., Wang, P., and Miao, C.Y. (2017b). NAD replenishment with nicotinamide mononucleotide protects blood-brain barrier integrity and attenuates delayed tPA-induced haemorrhagic transformation after cerebral ischemia. Br. J. Pharmacol. 174, 3823–3836.
[2] Yoshino, J., Mills, K.F., Yoon, M.J., and Imai, S. (2011). Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 14, 528–536.
[3] Caton, P.W., Kieswich, J., Yaqoob, M.M., Holness, M.J., and Sugden, M.C. (2011). Nicotinamide mononucleotide protects against pro-inflammatory cytokine-mediated impairment of mouse islet function. Diabetologia 54, 3083–3092.
[4] Gomes, A.P., Price, N.L., Ling, A.J., Moslehi, J.J., Montgomery, M.K., Rajman, L., White, J.P., Teodoro, J.S., Wrann, C.D., Hubbard, B.P., et al. (2013). Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155, 1624–1638.
[5] Peek, C.B., Affinati, A.H., Ramsey, K.M., Kuo, H.Y., Yu, W., Sena, L.A., Ilkayeva, O., Marcheva, B., Kobayashi, Y., Omura, C., et al. (2013). Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342, 1243417.
[6] Karamanlidis, G., Lee, C.F., Garcia-Menendez, L., Kolwicz, S.C., Jr., Suthammarak, W., Gong, G., Sedensky, M.M., Morgan, P.G., Wang, W., and Tian, R. (2013). Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure. Cell Metab. 18, 239–250.
[7] Choi, S.E., Fu, T., Seok, S., Kim, D.H., Yu, E., Lee, K.W., Kang, Y., Li, X., Kemper, B., and Kemper, J.K. (2013). Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT. Aging Cell 12, 1062–1072.
[8] Stein, L.R., and Imai, S. (2014). Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging. EMBO J. 33, 1321–1340.
[9] Yamamoto, T., Byun, J., Zhai, P., Ikeda, Y., Oka, S., and Sadoshima, J. (2014). Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion. PLoS One 9, e98972.
[10] Long, A.N., Owens, K., Schlappal, A.E., Kristian, T., Fishman, P.S., and Schuh, R.A. (2015). Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer’s disease-relevant murine model. BMC Neurol. 15, 19.
[11] Yoon, M.J., Yoshida, M., Johnson, S., Takikawa, A., Usui, I., Tobe, K., Nakagawa, T., Yoshino, J., and Imai, S. (2015). SIRT1-mediated eNAMPT secretion from adipose tissue regulates hypothalamic NAD(+) and function in mice. Cell Metab. 21, 706–717.
[12] Park, J.H., Long, A., Owens, K., and Kristian, T. (2016). Nicotinamide mononucleotide inhibits post-ischemic NAD(+) degradation and dramatically ameliorates brain damage following global cerebral ischemia. Neurobiol. Dis. 95, 102–110.
[13] de Picciotto, N.E., Gano, L.B., Johnson, L.C., Martens, C.R., Sindler, A.L., Mills, K.F., Imai, S., and Seals, D.R. (2016). Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell 15, 522–530.
[14] Lin, J.B., Kubota, S., Ban, N., Yoshida, M., Santeford, A., Sene, A., Nakamura, R., Zapata, N., Kubota, M., Tsubota, K., et al. (2016). NAMPT-mediated NAD(+) biosynthesis is essential for vision in mice. Cell Rep. 17, 69–85.
[15] Stromsdorfer, K.L., Yamaguchi, S., Yoon, M.J., Moseley, A.C., Franczyk, M.P., Kelly, S.C., Qi, N., Imai, S., and Yoshino, J. (2016). NAMPT-mediated NAD(+) biosynthesis in adipocytes regulates adipose tissue function and multi-organ insulin sensitivity in mice. Cell Rep. 16, 1851–1860.
[16] Lee, C.F., Chavez, J.D., Garcia-Menendez, L., Choi, Y., Roe, N.D., Chiao, Y.A., Edgar, J.S., Goo, Y.A., Goodlett, D.R., Bruce, J.E., et al. (2016). Normalization of NAD+ redox balance as a therapy for heart failure. Circulation 134, 883–894.
[17] Wang, X., Hu, X., Yang, Y., Takata, T., and Sakurai, T. (2016). Nicotinamide mononucleotide protects against beta-amyloid oligomer-induced cognitive impairment and neuronal death. Brain Res. 1643, 1–9.
[18] Yao, Z., Yang, W., Gao, Z., and Jia, P. (2017). Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease. Neurosci. Lett. 647, 133–140.
[19] Wei, C.C., Kong, Y.Y., Li, G.Q., Guan, Y.F., Wang, P., and Miao, C.Y. (2017a). Nicotinamide mononucleotide attenuates brain injury after intracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway. Sci. Rep. 7, 717.
[20] Li, J., Bonkowski, M.S., Moniot, S., Zhang, D., Hubbard, B.P., Ling, A.J., Rajman, L.A., Qin, B., Lou, Z., Gorbunova, V., et al. (2017). A conserved NAD+ binding pocket that regulates protein-protein interactions during aging. Science 355, 1312–1317.
[21] Wei, C.C., Kong, Y.Y., Xia, H., Li, G.Q., Zheng, S.L., Cheng, M.H., Wang, P., and Miao, C.Y. (2017b). NAD replenishment with nicotinamide mononucleotide protects blood-brain barrier integrity and attenuates delayed tPA-induced haemorrhagic transformation after cerebral ischemia. Br. J. Pharmacol. 174, 3823–3836.