Current research shows that this transformation between NR and NMN must take place for entry to a few cell types. This leads researchers to believe that NMN is, in fact, one of the quickest means of stimulating NAD production. However, NMN supplements are also proving to have their own anti-aging benefits beyond those of NAD production alone.
In addition to the NAD metabolic pathway, NMN can be added directly to cells without converting to NAD. This phenomenon is made possible by newly discovered transport proteins that increase in number after NAD levels drop off. In this form, NMN contributes to cell energy and allows each of the previously mentioned anti-aging properties promoted by cells with adequate ability to grow and regenerate.
Choosing to supplement with NMN along with NAD provides a much more direct path to promoting cell metabolism and is thus a much quicker means of doing the same. In addition, NMN has been found to improve insulin activity and production, resulting in additional metabolic benefits as well as glucose tolerance. In particular, NMN supplements can help work to alleviate metabolic conditions like diabetes, fatty liver disease, and obesity.
Once inside an animal’s cells, NMN feeds into the production of NAD+, which provides cells with needed energy and is thought to be critical for healthy aging. NAD+ also plays a key role in activating proteins that maintain the integrity of our DNA. Given its central role in so many cellular processes, the potential benefits of NMN extend to nearly all body systems. Below are some of the better-known examples.
Promotes Vascular Health and Blood Flow
We rely on our skeletal muscles for movement, stability and strength. To remain strong and in good condition, these muscles must consume significant amounts of key energy molecules, like glucose and fatty acids. Because NAD+ is required to metabolize these molecules, our muscles need a steady supply of its building blocks, such as NMN.
Studies in mice have shown that NMN protects against numerous aging-related declines in health, such as the stiffening of blood vessels, oxidative stress, our cells’ ability to keep dividing, and even changes in how active our genes are, what scientists call gene expression.
Improves Muscle Endurance and Strength
Studies have shown that mice fed NMN for extended periods of time had better energy metabolism with no obvious side effects. The health of our muscles grows ever more important as we age and our own supply of NAD+ declines.
Protects Against Heart Disease
At least your skeletal muscles get to take breaks. Not only can your heart not take a rest, it can’t even slow its pace much without causing serious problems. The heart’s energy requirement, therefore, is tremendous. And to keep it ticking, it needs to make all the NAD+ it can. This is why cardiac cells need a steady supply of NMN.
Lowers Risk of Obesity
Obesity is linked to a wide array of unhealthy conditions and can be very challenging to treat. There is no easy remedy for obesity and related conditions such as diabetes and metabolic syndrome. While lifestyle adjustments like consistent exercise and a healthy diet are of paramount importance, every little bit helps.
In mouse studies, NMN displays an effect that mimics aspects of calorie restriction (CR). Although CR has been shown to provide numerous benefits to aging and health, it is a difficult regime to maintain over a long period of time. Mimicking its benefits without adhering to such an extreme diet would be undeniably beneficial.
Enhances Maintenance of DNA Repair
The NAD+ made from NMN activates a group of proteins called sirtuins. Sirtuins, sometimes thought of as the guardians of our healthspan, play a key role in maintaining DNA integrity. Each time our cells divide, the DNA at the very ends of our chromosomes grows a tiny bit shorter. At a certain point, this begins to damage our genes. Sirtuins slow this process by stabilizing those end bits, known scientifically as telomeres. In order to function, however, sirtuins rely upon NAD+. Recent studies have shown that feeding mice NMN activated sirtuins and led to more stable telomeres.
Increases Mitochondrial Function
Simply put, we couldn’t live without our mitochondria. These unique cellular structures are known as the powerhouses of the cell. They convert molecules from the food we eat into the energy that our cells use. NAD+ is central to this process. In fact, mitochondrial anomalies caused by the loss of NAD+ may even impact neurological disorders such as Alzheimer’s. Studies done in mice have shown that NMN supplementation has rescued some mitochondrial dysfunctions.
A major advance in “systemic anti-aging medicine” is now available for supplementation in humans.
Nicotinamide riboside is a “next-generation” form of vitamin B3 that supports the vitamin’s functions throughout the body by boosting levels of a key metabolic cofactor called NAD+.
NAD+ is found in every single cell in the body, and is an absolute requirement for normal, efficient, and safe energy transfer from food to tissues.
New discoveries show that NAD+ is also essential for silencing genes for proteins that accelerate aging, such as those involved in inflammation, in fat synthesis and storage, and in blood sugar management.
Supporting NAD+ levels with nicotinamide riboside supplementation extends life span in laboratory organisms, while boosting energy, physical performance, and cognition in aging animals.
To fight aging throughout your body by restoring youthful function of basic life-sustaining processes in every single cell, begin regular supplementation today with nicotinamide riboside.
Pitting NR and NMN against each other is, for now, somewhat of a moot point because the two molecules have never been studied side by side in humans. The biggest, and most obvious, difference between NMN and NR is size. NMN is simply larger than NR, meaning it often needs to be broken down to fit into the cell. NR, when compared to other NAD+ precursors (like nicotinic acid or nicotinamide) reigns supreme in efficiency.
Nmn Pathways Graph2
But give NMN a new door, one it can fit through, and it’s a whole new game. This is where cellular transporters come into play. Transporters are proteins that are doors on the cell; they allow molecules to enter the cell without needing to chemically transform.
The latest research from Shin-ichiro Imai, M.D., Ph.D., a professor of developmental biology at Washington University in St. Louis, identified a transporter that allows NMN to get into the cell without converting to NR. The catch? The transporter is only on cells located in the gut of mice and only works in the presence of sodium ions. NR, however, has been shown to enter cells in the liver, muscle, and brain tissue of mouse models. (To date there is not yet evidence that these mouse studies can be extrapolated to humans) But again, the two have never been matched up against each other in a way that can truly identify one as superior to the other.
in an effort to stave off these age-related changes, can we boost NAD+ levels by taking NAD+ supplements? Not quite. NAD+ in supplemental form has very poor bioavailability, meaning it doesn't have much of an effect when introduced to the body. But, NAD+ has several precursors or intermediates—molecules that transform into NAD+ through enzymatic reactions. Scientists have studied two such intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), more extensively than others, and the research is encouraging. Several studies indicate that supplementing with these precursors can increase NAD+ levels and prolong the lifespan of yeast, worms, and mice.[2-4] Furthermore, other animal studies show that boosting NAD+ can also improve muscle generation, cardiovascular function, and glucose metabolism.[4-6] But it's critical to remember that findings in animal studies don't necessarily translate to humans. So let’s examine the clinical research currently published.
Supplementing NMN may be an effective nutraceutical anti-aging intervention, with beneficial effects on a wide array of physiological functions.
In numerous mouse models of disease and aging, NMN has demonstrated a wide array of remarkable effects, benefitting conditions ranging from diabetes to Alzheimer’s disease to ischemia.27 Orally
administered NMN is quickly synthesized into NAD+ in tissues in mice. NMN has been able to suppress age-associated weight gain, enhance energy metabolism and physical activity, improve insulin sensitivity, improve eye function, improve mitochondrial metabolism and prevent age-linked changes in gene expression.28 In mice bred to be diabetic or obese, NMN improved both the action and secretion of insulin.29 NMN also protected the mouse heart from ischemia and/or reperfusion injury.30 It has restored skeletal muscle in aged mice31, and slowed cognitive decline in a mouse model of Alzheimer’s disease, by improving the survival of neurons, improving energy metabolism, and reducing reactive oxygen species.32 It may help maintain the integrity of the blood brain barrier.33 NMN is likely a good candidate to suppress inflammaging—the increase in inflammation associated with aging—since studies show it lowers adipose tissue inflammation associated with age. In fact, older mice appear to be more responsive to NMN, in comparison with young mice.
NMN appears to be stable in water; in one study 93%–99% of NMN was maintained intact in drinking water at room temperature for 7–10 days. NMN also appears to be rapidly absorbed. When given to mice by oral gavage, there was a steep increase of plasma NMN in a mere two and a half minutes, with further increases at 5-10 minutes. Plasma levels then declined to baseline, suggesting rapid absorption in the gut.29 Long-term (1-year) NMN given orally, in doses of up to 300 mg/kg, was found to be safe and well tolerated in normal mice.
NMN has gained a lot of attention lately, especially after the release of David Sinclair’s book Lifespan. In his book, the Ph.D. and longevity scientist discusses his research examining NMN, particularly in mice. He has been very open about taking NMN, but has also made it clear that he has no opinion on whether anyone else should take the supplement. Similar to NR, the research in animal studies looks promising, but the first study in humans was only published this year. Phase I of this study merely assessed the safety of NMN supplementation, and therefore NAD+ levels were not even measured. Ten healthy Japanese men received a single dose of 100mg, 250mg, and 500mg of NMN on separate occasions. All quantities were tolerated without adverse side effects. The authors concluded that up to 500mg of NMN is safe in healthy men. For phase II, researchers will reportedly examine the efficacy of NMN, as well as appropriate dosage and frequency; however, it remains unclear if this study has started.
Nicotinamide riboside is likely safe with few — if any — side effects. In human studies, taking 1,000–2,000 mg per day had no harmful effects.However, most human studies are short in duration and have very few participants. For a more accurate idea of its safety, more robust human studies are needed.
Some people have reported mild to moderate side effects, such as nausea, fatigue, headaches, diarrhea, stomach discomfort and indigestion.In animals, taking 300 mg per kg of body weight (136 mg per pound) daily for 90 days had no harmful effects.
What’s more, unlike vitamin B3 (niacin) supplements, nicotinamide riboside should not cause facial flushing.
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