A short introduction to the principles of NAD+ & NMN
* This image is a visualization of UltraSpec Lab cell data simulation, each line represents a human biochemical reaction.
Intro
We are glad that you are interested in the science behind healthy products. This article is not for biochemistry experts, but for unprofessional consumers. If you are interested in the cutting edge of human anti-aging achievements, we hope this article will take you deeper into this revolutionary field of research.
We know that all technological advances in human history, especially those where the results are hard to see directly with the naked eye, have been subjected to a long and demanding process of questioning, and the same goes for NAD+ and NMN. If you follow the field a little, you will notice a lot of skepticism and opposition. But please don't jump to conclusions.
You can choose to wait and let time tell, or you can experience amazing anti-aging results right away.
Understand Aging
We all know that all living things will inevitably age. But what exactly does "aging" mean? Is it simply the increase in age? If it is just age, then why can two people of the same age have completely different physical appearances?
This is because the objective age increases and the degree of aging of the body is not exactly equal. In other words, the objective age of a person does not coincide with the degree of aging of his body. When we say "aging", we are not referring to an increase in age, but to a series of changes in the body, such as a decline in mental status, an increase in skin wrinkles, graying and loss of hair, loss of vision and hearing, etc.
Our UltralSpec lab offers a state-of-the-art "AI-based epigenetic age quantification service" that accurately tests the true biological age of the human body. To learn more about this service, please click here.
Two types of aging
As a whole, we classify aging into "exogenous aging" and "programmed aging".
"Exogenous aging" refers to the aging of physical characteristics caused by the external environment, the most common of which is "skin photoaging".
"Programmed aging"(also known as "natural aging") is a natural process that humans have not understood and cannot resist.
Exogenous aging is mostly reflected in the changes of the body's appearance, while programmed aging is mainly reflected in the decline of the body's internal functions.
Can we resist aging?
Everyone wants to stay young forever, and the fight against aging is a theme that has been explored by humans since ancient times. However, most of our efforts to combat aging have been limited to fighting "exogenous aging".
These include external interventions such as skin care products, injectable fillers, and surgical procedures, as well as internal interventions such as collagen-containing nutrients and anti-glycation products.
Although all of these means of combating exogenous aging are effective, the side effects, risks and limitations are obvious. Human In order to fight against aging, we must overcome the persistent problem of "programmed aging".
What is NAD+?
Nicotinamide adenine dinucleotide (NAD+) is present in all living cells. Nicotinamide adenine dinucleotide (NAD+) is the active form of vitamin B3. While dietary supplements of common forms of B3 (such as niacin and nicotinamide) have been available for decades, however, there is substantial scientific evidence being presented for newer and more specialized forms such as nicotinamide mononucleotide (NMN) as well as nicotinamide riboside (NR) in some key aspects of the fight against cellular aging.
NAD+ is involved in many cellular processes, including energy production, cellular repair, and optimization of overall cellular function. Even with adequate intake of niacin or niacinamide, NAD+ levels decline with age, so supplementation of depleted NAD+ is beginning to become part of a strategy to reverse aging and promote cellular health.
What is the function of NAD+?
NAD+ is one of the most important molecules in the body and is known as the "universal electron carrier" in the human body. Water is known as the "universal solvent". Both are equally necessary for our health.
To understand NAD+, we must first understand hydrogen. A hydrogen atom consists of a positively charged proton and a negatively charged electron. If a hydrogen atom loses an electron, it becomes positively charged. If it gains an extra electron, it becomes negatively charged. If there is a pairing of a proton with an electron, hydrogen is uncharged.
The + in NAD+ indicates that the NAD molecule is positively charged because it contains a positively charged hydrogen proton with no electron. In some chemical reactions, NAD+ can accept a negatively charged hydrogen that contains the two electrons that form NADH. Like a coin with two sides, NAD+ and NADH are called "redox couples", a term used to describe two forms of the same molecule (gaining or losing electrons). Redox reactions involve the gain or loss of electrons. In the process of changing NAD+ to NADH, the net gain is a negatively charged electron that is used to neutralize the positive charge of NAD+. Because NADH has no charge, it has no + sign. It is uncharged, but still important.
NAD+ is vital for generate energy
Both NAD+ and NADH are critical for the proper functioning of human cells. They are necessary for generate energy. They are also necessary for the conversion of molecules into active forms. For example, coenzyme Q10 is one of the most important cellular antioxidants and is required for cellular energy production in the mitochondria. After completing its work, coenzyme Q10 is converted from the active form (ubiquinol) to the inactive form (ubiquinone). To convert coenzyme Q10 to the active form again, NADH provides one hydrogen and one electron (ubiquinone) to form ubiquinol. An oxygen molecule absorbs an additional electron and NADH is converted back to NAD+.
NAD+ is involved in a different reaction than NADH. Cells need them because NADH cannot do what NAD+ can do, and vice versa. Cells need NAD+ and NADH to generate cellular energy and to construct or repair molecules, including DNA, cell membranes, proteins and hormones.
The difference between NAD+ and NADH
NAD+ and NADH function on different molecules. NAD+ is particularly important in enabling some specific compounds that regulate cellular function to function. For example, NAD+ is necessary for sirtuin to maintain normal function. Without NAD+, these cellular proteins cannot be initiated to fight cellular senescence and regulate inflammation. sirtuin initiated by NAD+ also promotes proper metabolism, including blood glucose control and body weight.
Another major age-reversing effect of NAD+ is to slow down the genetic clock running within each cell. This biological clock determines when aging begins and uses the length of telomeres as a signal. Telomeres are segments of DNA (our genetic material) that are compounded at the ends of chromosomes. The shorter the telomere, the greater the effect on gene expression. The result is cellular aging. NAD+ is one of the key compounds against telomere shortening.
Consequences of aging and reduced NAD+ levels
NAD+ is a very important cellular molecule. One of the reasons why cells begin to lose their normal function as people get older is that NAD+ levels decline with age.Decreased NAD+ levels may lead to
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Decreased metabolism, leading to weight gain and poor blood sugar control
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Fatigue
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Decreased vascular health
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Age-related muscle loss (sarcopenia)
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Age-related memory loss and mental decline
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Age-related vision and hearing loss
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Prevention of age-related decreases in NAD+ levels
The main reason for the decline in NAD+ levels with age is chronic inflammation. The term inflammatory aging (inflammaging) is used to denote the adverse effects of chronic low-grade inflammation on accelerated aging.
One of the consequences of inflammatory aging is a decline in NAD+. Inflammation leads to an increase in a cellular enzyme called CD38. This enzyme degrades NAD+ and its precursors. Fortunately, plant polyphenols (e.g. resveratrol, quercetin, lignan, etc.) can reduce CD38 activity.
Another important factor in maintaining NAD+ levels is the switch from NADH back to NAD+ when NADH accepts an electron. A specific enzyme called NQO1 is able to repair NAD+. The importance of this conversion is obvious because the NQO1 gene is known as the "longevity gene".
NQO1 works in concert with NADH to convert coenzyme Q10 from its inactive form (ubiquinone) to its active form (ubiquinol), in the process also producing NAD+. functions.
Increasing the expression of the NQO1 gene is an important goal in reverse aging. This goal can be achieved by inducing a protein called Nrf2 as well as by reducing BET proteins. Again, polyphenols (specifically resveratrol) can help reach this goal. Since resveratrol can directly increase NQO1 activity while increasing Nrf2 as well as reducing BET proteins, CD38 and inflammation, there is a strong case for using resveratrol and NAD+ precursors to increase NAD+ levels.
In addition, resveratrol would exert its own direct effects and enhance the anti-aging effects of sirtuin. According to clinical studies, resveratrol may contribute to the alleviation of inflammatory disorders and improve mental function. The usual dose of resveratrol is 500 to 1000 mg per day.
Boosting NAD+ levels with NMN and NR
Due to the critical importance of NAD+ for normal cellular function and for the retrograde aging process, strategies to boost NAD+ with nicotinamide mononucleotide (NMN) and nicotinamide ribosome (NR) supplementation are becoming increasingly popular.
Studies have shown that these two fortified forms of vitamin B3 are effective in increasing NAD+ levels and maintaining them with continued use. In fact, NR and NMN are referred to as NAD+ boosters in the medical grade literature because of their effectiveness in increasing NAD+ levels.
Many pre-clinical studies have shown that NR and NMN can optimize various features typical of cellular senescence. The growing number of scientific studies on this subject, with over 100 studies currently available, has generated a great deal of interest in the age-reversing effects of NMN and NR. Several human clinical trials are validating these effects. Currently, more than 40 human clinical trials of NMN or NR are underway to evaluate the multiple health benefits, including optimization of brain function, cardiovascular system, and metabolism. So, more data will be available soon. The available data are already quite encouraging.
Which one should be used, NMN or NR?
Most of the available clinical human data use the nicotinamide ribosome (NR), focusing on its effects on cognitive function, mood, metabolism, oxidative stress, vascular health, liver health, and glycemic control. A total of nine human clinical trials of NR have shown an increase in NAD+ levels, but overall have not yielded consistent results in optimizing a variety of health issues.
NR has been found to be particularly consistent in optimizing brain function and promoting vascular health. Many experts consider nicotinamide mononucleotide (NMN) to be an excellent NAD+ booster, with a particularly well-known brand being Dr. David Sinclair of Harvard University, who personally takes 1,000 mg per day (as well as 1,000 mg of resveratrol). There are many reasons to believe that NMN has a better clinical effect than NR.
While both NR and NMN raise NAD+, NMN is claimed to have some advantages. Because NMN is one step closer to the manufacture of NAD+ and because a specific transporter has been identified that can deliver NMN directly to cells, NMN may be better utilized than NR. In contrast, although some oral NR is delivered to tissues in its native form, it now appears that most of the ingested NR is broken down into conventional nicotinamide. This may be a problem because it leads to some feedback mechanism that impairs NAD+, and nicotinamide is a highly efficient control agent of sirtuin activity.
Oral NR is mostly converted to nicotinamide, which may be one of the reasons why animal experiments have shown stronger and more widespread effects of NMN than NR. For example, in a study conducted in mice, NMN showed extensive optimization in terms of age-related physiological decline. Mice given NMN for more than one year were found to have optimized mitochondrial and metabolic function, insulin sensitivity and lipid metabolism, bone density, vision and immune function. Mice that were given NMN also had an 80% increase in endurance and physical performance. NR did not bring about these effects.
In a mouse model of brain aging, both NMN and NR reduced the accumulation of beta-amyloid, a key compound that leads to impaired brain function. NR has a clear advantage here, as it was shown to also improve cognitive performance.
In addition to Dr. David Sinclair of Harvard University, another principal investigator of NMN is Dr. Mari Ichiro Imai of the Washington University (St. Louis University, Missouri) School of Medicine. His research on mice has shown that NMN is effective in slowing the signs of aging as well as boosting energy and metabolism. Dr. Imai says that if these appear in mice translate to humans, that means supplementation with NMN may significantly increase biological age (indicating the body's functional status, as measured by various biomarkers) in humans.
Dosage and side effects
In general, the doses of nicotinamide mononucleotide (NMN) used in the study were 250 to 500 mg per day; while the dose of nicotinamide riboside (NR) was 1000 mg per day. According to the study, these dose levels were shown to be well tolerated with no side effects or drug interactions.
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