by Dr.Harald Wiesendanger– Klartext
What the mainstream media is hiding
You can spend a fortune on anti-aging products – with questionable benefits and uncertain side effects. NMN seems to be a notable exception. The more deeply this substance is researched, the more clearly its spectacular potential to keep us healthy and vital even as we get older becomes clear.
“I want to grow old with you,” is what it says on a funny postcard that shows an elderly couple taking a leisurely walk on a dirt path, pushing walkers in front of them. “But there’s no rush.”
Almost everyone wants to grow old, but hardly anyone wants to be old. At least in Western industrialized countries, older age is almost a synonym for physical limitations and mental decline, for chronic illness and disability, for canes, pill boxes, and hearing aids, for loss of freedom and need for care – with seemingly natural inexorability. Just “age-related”.
With such gloomy prospects, the good news from the most famous aging researcher on our planet, David Sinclair, Australian-born biologist and professor of genetics at Harvard Medical School in Cambridge, Massachusetts, is all the more encouraging. Growing old is a curable disease, he teaches. (1) No one embodies the imminent victory over supposed fate more convincingly than himself: with full, not even remotely gray hair and almost wrinkle-free skin, slim, energetic, and in great shape, the now 54-year-old with his mischievously grinning face looks as if he were a rascal just in his early thirties.
What is Sinclair’s secret? He has several. Three letters stand for one thing: NMN, an abbreviation for nicotinamide mononucleotide. He swallows several hundred milligrams of it every morning, alongside a handful of blueberries in homemade yogurt. How does he come to this?
NMN is not artificial. It is a molecule that occurs in plants as well as in mammals, including humans – in every single cell. As a nucleotide, it is the smallest building block of nucleic acids, the basic chemical component of DNA and RNA. Our body is able to produce it itself: from vitamin B3, from the amino acid tryptophan, also with the help of intestinal bacteria.
Our organism converts this NMN into nicotinamide adenine dinucleotide, or NAD+ for short, a so-called cofactor, the necessary non-protein element of an enzyme and essential for its task of triggering biochemical reactions in us. Our organism needs NAD for various functions, including producing energy from food. As a versatile information shuttle, it transports protons and electrons back and forth through every cell. It strengthens the mitochondria, the power plants of our cells. In addition, NAD helps to repair damaged genetic material, regulate genes, strengthen the cells’ defense systems, and adjust our internal clock. (Q13) NAD participates in the activity of more than 500 enzymes; Without it, we would be dead within 30 seconds.
Unfortunately, as we age, we produce less and less NAD, and this has fatal consequences: a falling NAD level accelerates the aging process and contributes to numerous chronic diseases, from arteriosclerosis to type 2 diabetes and Alzheimer’s.
What happens if you quickly correct the deficiency – supply the organism with more NAD? David Sinclair and his team from Harvard Medical School in Cambridge, Massachusetts, initially researched this in mice. It turned out that a sufficiently high supply of NAD through the feed can stop the harmful degradation processes and even partially reverse them. After just one week, the signs of aging disappeared, as can be seen in parameters such as inflammatory reactions, insulin resistance, and muscle loss. After the NAD treatment, the cells of two-year-old mice suddenly resembled those of six-month-old mice. Old mice turned into reindeer, turning their wheels faster and more persistently than ever before. At lectures, Sinclair likes to present side-by-side pictures of two lab mice: one gray and shaggy, the other brown and perky – both born on the same day.
Since Sinclair’s groundbreaking experiments, extensive further research on mice and rats has confirmed how positive effects the administration of NAD or its precursor NMN has on their health: energy metabolism increases, physical activity increases; The genetic material is protected from mutations, age-related weight gain is avoided, insulin sensitivity is increased, and the risk of type 2 diabetes is reduced. Inflammation and degenerative changes in the nervous system become less common. (2) New blood vessels formed. The muscles were supplied with more oxygen and lactic acid, and toxins were better removed. The frailty disappeared. Last but not least, the lifespan of laboratory animals is extended significantly.
Encouraged by these observations, longevity researchers are increasingly looking to test NMN in humans, with astonishing results.
NMN generally makes you healthier
In a study published at the end of 2022, 80 healthy middle-aged adults with age-typical NAD levels received 300 mg, 600 mg, or 900 mg of NMN – or a placebo – daily for two months. Compared to the control group, NMN users were physically fitter at the end of the test – they walked a longer distance within a six-minute period. They rated their general health significantly better: For example, they felt more comfortable in their own skin, more emotionally stable, happier, and more productive. Their insulin resistance, a main cause of type 2 diabetes, was less pronounced: their body cells responded more readily to signals from the hormone insulin. Their biological aging was slowed, as their blood samples revealed on 19 laboratory parameters, from albumin and hematocrit to HDL and LDL cholesterol to platelets and erythrocytes. These benefits were most pronounced at NMN doses of 600 and 900 mg.
NMN slows down the aging process
NMN can also slow down and possibly even reverse biological aging in humans. It works through sirtuins, a family of proteins found in all living things. They allow themselves to be activated by NMN under stress, such as a lack of nutrients, cold, or physical exertion. Then, they turn on longevity genes that protect, repair, and renew. They “suppress epigenetic changes and allow the youth program to continue,” as Sinclair noted. (3) “NAD+ is the closest thing to a fountain of youth,” he enthused in Time Magazine.
Among other things, NMN influences the length of telomeres, the end caps of our chromosomes, which protect them from all kinds of damage, such as oxidative stress and free radicals. As we age, they become shorter and shorter. In a Chinese study, eight healthy men between 45 and 60 years old took 300 mg of NMN daily with breakfast for a quarter of a year. After just the first month, the telomeres of the immune cells in the blood had lengthened significantly.
NMN protects against diabetes
In two studies, subjects received 250 mg of NMN daily for 10 and 12 weeks, respectively. Ultimately, her insulin sensitivity improved significantly, and her blood sugar levels were regulated. (4)
NMN heals the intestines
What animal experiments indicated is being confirmed more and more in human studies: daily intake of NMN over several weeks is sufficient to counteract and prevent chronic inflammatory bowel diseases, to remediate disturbed intestinal flora, and to repair a weakened or more permeable intestinal barrier – the leaky gut. Syndrome – to restore. Digestion improves, and more bile acid is produced.
NMN also ensures that beneficial intestinal bacteria multiply, including Lactobacilli, Bifidobacteria, Firmicutes, and Akkermansia. (5) These are good for our intestines in several ways: They produce a layer of mucus that lines it and protects the intestinal barrier – this becomes more stable and allows fewer harmful substances to pass through. By colonizing the intestinal wall, the bacteria prevent harmful germs from multiplying. They form short-chain fatty acids (SCFAs) such as butyric and propionic acid, which, among other things, nourish the cells of the intestinal wall. Absorbed into the blood through the intestinal mucosa, they fight inflammation throughout the body and even protect the blood-brain barrier.
NMN protects against dementia
The composition of the intestinal flora affects the central nervous system via the so-called “gut-brain axis” – the connection that neurally networks both organs. At least in animal experiments, it has already been shown that several signs of Alzheimer’s disease in the brain were significantly reduced after NMN administration: less inflammation, improved mitochondria function, more efficient signal transmission between nerve cells, and a smaller decline in cognitive performance.
NAD booster as a universal medical weapon
There is a graphic on Sinclair’s homepage that illustrates how much the pop star of longevity research believes can be achieved using NAD boosters beyond the applications mentioned:
By administering NAD, the liver could be made to break down fatty acids better. The endothelium, the cell layer on the inside of the blood and lymph vessels, could be optimized, as could insulin production in the pancreas and lipogenesis in fatty tissue. The heart and kidneys would receive more protection. Rejuvenated reproductive organs could extend or restore the period of fertility. Mitochondrial functions could be boosted, cells rejuvenated, the immune system strengthened, cancer prevented, Nerves could regenerate, wounds could heal more quickly, and inflammation could subside more rapidly. Whatever works increasingly poorly in our bodies, the cause usually seems to be one and the same: aging. For Sinclair, one thing is certain: There is no worse health risk than increasing the time between births. “My mother was a smoker,” he says. “This increased their risk of cancer fivefold. But: By aging from 20 to 70 years old, you increase your risk of cancer a thousand-fold. We must target aging itself.” (6)
Anyone who finds the key to stopping or even reversing age-related decline will not only have conquered one or another chronic illness but also chronic illness itself. As soon as this is possible, it must happen. Sinclair’s ideology is that “every person has the right to the best medical care and a maximum life expectancy.”
Quote: “As a species, we are living much longer than ever. But not much better. Not at all. Over the past century, we have gained additional years, but not additional life—not life worth living anyway.5”- “What if we didn’t have to worry that the clock was ticking? And what if I told you that soon—very soon, in fact—we won’t?”― David A. Sinclair, Lifespan: Why We Age—and Why We Don’t Have To
“I think it would be nice to still experience the 22nd century. That would mean I would have to make it to my 132nd birthday. For me, this doesn’t seem beyond the rules of biology. And if I make it that long, I might want to live even longer.”
Apparently, it is free of side effects.
No effect without side effects? At least concerning NMN, the following applies No rule without exception. Neither animal experiments nor human studies have revealed any harmful effects – at least not at the commonly administered amounts of between 250 and 900 milligrams per day. (David Sinclair personally prefers 1000 mg.)
In rats, intolerance reactions only occurred with an extremely high NMN intake of 2000 milligrams per kilo of body weight; then, they ate less and lost weight. According to a common conversion method to determine the “human equivalent dose” (HED), 2000 mg per kilo of rat body corresponds to 323 mg/kg human body weight. Those of us who weigh 60 kilos could safely consume up to 19,380 mg of NMN daily. In the studies mentioned, however, the effective dosages were many times lower.
What to make of the rumors circulating online that NMN increases the risk of cancer? No study has proven this to date; on the contrary, Because NMN or the NAD+ formed from it helps repair DNA damage, it also eliminates a significant cause of cancer development. In animals that were already sick, it was shown that NMN administration does not promote tumor growth but inhibits it because it activates natural killer cells.
Why not naturally?
If we largely cover our NMN needs through food when we are younger, couldn’t a consistent change in the diet be enough as we get older? Then why don’t we eat more foods that contain NMN – or vitamin B3 or the amino acid tryptophan, from which our body can produce NMN and NAD?
Rich sources of vitamin B3 include mung beans, peanuts, mushrooms, legumes and potatoes, eggs, offal, and fish such as anchovy, tuna, salmon, and mackerel. (7) NMN is particularly abundant in edamame, a Japanese soybean (up to 1.88 mg per 100 grams), but also in avocados (up to 1.60 mg), broccoli (up to 1.12 mg), cabbage (up to 0 .9 mg), raw beef (up to 0.42 mg) and tomatoes (up to 0.3 mg).
Getting some of it on your plate every day, and in generous quantities, is of course not for everyone. In addition, there is no experimental evidence to date to suggest that there are disadvantages to taking NMN as a dietary supplement instead.
However, no culinary enjoyment is associated with it: commercially available NMN is a fine, snow-white, almost tasteless powder that feels like household flour in the mouth.
Excellently bioavailable
What does our body do with NMN? To what extent can he actually use it? He may excrete it immediately – like the recently hyped spermidine, a messenger substance that is considered an excellent anti-aging agent. “You can take it, but it doesn’t reach the body at all,” as a study from the University of Lübeck suggests.
But these concerns also seem unfounded, at least in the case of isolated NMN. Swallowed as a dietary supplement, the intestines absorb it within a few minutes and enter the bloodstream. Animal experiments showed increased NMN levels in the tissue after just 10 to 30 minutes. After just one hour, the NAD levels had increased. (8) In healthy people between the ages of 20 and 65, a Japanese study found that those who consume 250 mg of NMN daily increase their NAD levels by an impressive 40%. As soon as he stops taking the drug, the blood values return to the starting point.
How should you take it? Sinclair recommends not swallowing it right away, but rather keeping it under your tongue for a minute or two. Then, the mucous membrane in the mouth can partially absorb it and transport it into the bloodstream.
Steep price
Unfortunately, certified NMN of the best quality, continuously tested by accredited analysis laboratories with a purity level of over 99%, is unavailable in the bargain hall. At a highly acclaimed online retailer, Age-Science, 100 grams cost a hefty 129 euros, including shipping and VAT. (The smallest bag size, with 12.5 grams of NMN powder, was available there in November 2023 for 30 euros.) Stored cool and unopened, it has a shelf life of at least two years.
If you want it to be significantly cheaper, you are taking an incalculable risk. Complaints are increasing that suppliers from overseas and cheap ones are adding ascorbic acid, milk powder, or something else to their supposedly “pure” NMN. In autumn 2021, 22 different providers were tested in the USA – with devastating results: almost two-thirds did not offer any real NMN or only offered inferior NMN.
It is best to use a milligram scale for measuring. Laboratory scales are available online for just 15 euros.
First, think about it, then buy it.
Around the globe, people in good health, free of all the dreaded diseases of civilization, fit and vital, reach an almost biblical age – without NMN and other popular anti-aging products. Instead of jumping straight into every supposed pharmaceutical fountain of youth, we would do well to investigate the secret of the “Centenarians,” the cheerful centenarians. (9) It is as unoriginal as it is timelessly true: eat less and wholesomely, drink enough pure water, be physically active in the fresh air, sleep well, avoid recreational drugs, reduce stress, be integrated into stable social networks, busy with a task, fulfilled of one meaning. (See CLEAR TEXT: “Even Methuselahs don’t give a damn about Corona.”)
David Sinclair takes all of this into account instead of just instilling a sophisticated mixture of pills that have not yet been proven beyond doubt to actually prolong the life of anyone who is not a mouse. (In addition to NMN, he also swallows a gram of resveratrol – the suspected anti-aging ingredient in red wine – and a gram of metformin, a diabetes drug that studies have shown also works against dementia, cancer and heart disease.) (10) He fasts regularly, eats too little rather than too much, eats a lot of vegetables and rarely red meat, and stays away from ready meals. He usually skips lunch. He avoids sugar and carbohydrates. It supplements vitamin D and K2. He gives himself 83 mg of aspirin every evening to thin his blood. He drinks plenty of green tea. He does not smoke. He usually doesn’t have the time for exercise – but he never misses the stairs. On weekends, he works out in the gym and sweats in a sauna before climbing into an ice-cold pool. Not only at night when he sleeps but also during the day, he tries to stay in a cool environment. He has blood drawn every few months to check dozens of biomarkers. If the values are not optimal, he corrects them by changing his diet and exercising. (11) He is the proud father of three children, has a large circle of friends, and Charlie, a pampered poodle mix. He enjoys the highest recognition in his professional environment. He shines not only as a scientist but also as a businessman: in 2008, Sinclair sold his company Sirtris Pharmaceuticals to the pharmaceutical giant GlaxoSmithKline (12) for a whopping $720 million. To date, he manages five other self-founded biotech companies. He is fulfilled by work in which he achieves something significant, even groundbreaking.
You certainly won’t stay young forever with all of this. But possibly well until the end. How desirable would a scientific victory over a death that could put a meaningful end to such a full life?
(Harald Wiesendanger)
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Remarks
1 Siehe David A. Sinclair: Das Ende des Alterns. Die revolutionäre Medizin von morgen, Köln 2019.
2 X. Zhu u.a.: “Nicotinamide mononucleotides alleviated neurological impairment via anti-neuroinflammation in traumatic brain injury. International Journal of Medical Sciences 2023;20(3):307-317, https://www.researchgate.net/publication/367969386_Nicotinamide_mononucleotides_alleviated_neurological_impairment_via_anti-neuroinflammation_in_traumatic_brain_injury; X. Zhao u.a.: “Nicotinamide mononucleotide improves the Alzheimer’s disease by regulating intestinal microbiota “, Biochemical and Biophysical Research Communications 2023;670:27-35, https://www.sciencedirect.com/science/article/abs/pii/S0006291X23006538)
3 Das Ende des Alterns, a.a.O., S. 197.
4 T. Yamane u.a.: “Nicotinamide mononucleotide (NMN) intake increases plasma NMN and insulin levels in healthy subjects “Clinical Nutrition ESPEN. 2023;56:83-86, https://www.sciencedirect.com/science/article/pii/S2405457723001249; M. Yoshino u.a.: “Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women “Science. 2021;372(6547):1224-1229, https://www.science.org/doi/10.1126/science.abe9985
5 P. Huang u.a.: “NMN Maintains Intestinal Homeostasis by Regulating the Gut Microbiota “, Frontiers in Nutrition 2021;8:714604. https://www.readcube.com/articles/10.3389/fnut.2021.714604; 26: Huang P, Wang X, Wang S, et al. Treatment of inflammatory bowel disease: Potential effect of NMN on intestinal barrier and gut microbiota “, Current Research in Food Science 2022;5:1403-1411, https://www.sciencedirect.com/science/article/pii/S2665927122001289?via%3Dihub
6 Zit. nach Nach SZ-Magazin Heft 37/12.9.2019: “Für immer jung!”, https://sz-magazin.sueddeutsche.de/gesundheit/david-sinclair-harvard-alter-forschung-jung-bleiben-87755?reduced=true, leider nur hinter einer Bezahlschranke.
7 M. Hrubša u.a.: „Biological Properties of Vitamins of the B-Complex, Part 1: Vitamins B1, B2, B3, and B5“, Nutrients 2022;14(3):484, https://www.mdpi.com/2072-6643/14/3/484; siehe auch https://www.gesundheit.gv.at/leben/ernaehrung/vitamine-mineralstoffe/wasserloesliche-vitamine/niacin.html#wo-ist-niacin-enthalten
8 K. F. Mills u.a.: “Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice “, Cell Metabolism 2016;24(6):795-806, https://pubmed.ncbi.nlm.nih.gov/28068222/ ; J. Yoshino u.a.:N “icotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice “, Cell Metabolism 2011;14(4):528-536, https://profiles.wustl.edu/en/publications/nicotinamide-mononucleotide-a-key-nad-supsup-intermediate-treats-
9 https://www.spiegel.de/fotostrecke/langes-leben-hundertjaehrige-verraten-ihr-geheimnis-fotostrecke-143844.html; https://www.focus.de/gesundheit/longevity/langes-leben-das-steckt-hinter-dem-geheimnis-der-100-jaehrigen_id_193860574.html
10 Nach SZ-Magazin Heft 37/12.9.2019: “Für immer jung!”, a.a.O., https://sz-magazin.sueddeutsche.de/gesundheit/david-sinclair-harvard-alter-forschung-jung-bleiben-87755?reduced=true Siehe auch https://fastlifehacks.com/david-sinclair-supplements/
11 Näheres über Sinclairs persönliches Gesundheitsprogramm in Das Ende des Alterns, a.a.O., S. 401.
12 Kate Holdsworth: Cosmos Bright Sparks: Australia’s top 10 young minds (Memento vom 26. Dezember 2013 im Internet Archive), Cosmos, 26. Juli 2006
Featured image: Freepik.
Porträtfoto Sinclair: Von Editor5627 – Eigenes Werk, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=128703620
P.S.: I underline the general disclaimer in this article. I wrote it based on studies that were current at the time of publication. However, it is not intended for self-diagnosis or self-treatment and does not replace a visit to your doctor. Therefore, always discuss any medical procedure discussed in this or any other article on my blog with your trusted doctor first.