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Today, we want to highlight a recent human trial of the popular
supplement nicotinamide riboside, a compound that has been shown in mice
to restore NAD+ levels. The compound has had impressive results against some aspects of aging in mouse studies, and there is now some more data for NR in humans [1].Nootropics Powder What is nicotinamide riboside? Nicotinamide adenine dinucleotide (NAD+) is a chemical that facilitates the production of energy from sugar and is present in every cell in our body. As well as being important in energy production, it is also involved in DNA repair, cellular signaling, and many other cell functions. Unfortunately, as we age, the availability of NAD+ declines in the body, and this appears to support the development of metabolic disorders and other age-related diseases. It is involved in many systems in the body, from useful ones, such as DNA repair, to potentially harmful ones, such as inflammation caused by senescent cells. Due to this, it is currently unknown if increasing NAD+ signaling will cause more harm than good – more work, such as the study being reported, must be done before we have an answer. NAD+ can be created de novo, going through multiple enzymatic steps in the de novo pathway (kynurenine pathway), ultimately producing nicotinic acid mononucleotide (NaMN) as the final step in this process. The term “de novo” means that one biomolecule, in this case, NAD+, is produced anew from a different molecule. Essentially, the NaMN molecule is built from scratch, starting with the essential amino acid L-tryptophan (Trp). The de novo pathway is the only non-vitamin B3-based pathway that allows the creation of NAD+. Niacins, such as nicotinic acid- and niacinamide-containing compounds, are taken in via dietary sources or supplements and can be used to create NAD+, with each form entering the system at different points. Nicotinic acid (NA) and nicotinic acid riboside (NAR) produce NAD+ via the Preiss-Handler pathway. This pathway begins with NA or NAR and converts both into NAD+ via a series of enzymatic steps. As this diagram shows, NaNM is an intermediate in the pathway, meaning that the de novo pathway shares several common enzymatic steps with the Preiss-Handler pathway on the road to NAD+ creation. The final pathway is the salvage pathway, which converts niacinamide (NAM) into NAD+ through a series of steps that continually cycle and recover the NAD+ once it has been used by the cell, turning it back into NAM to create NAD+ again; hence, it is called the salvage pathway. Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) also both feed into the salvage pathway and are converted into NAD+. Nicotinamide phosphoribosyltransferase (NAMPT) is also a precursor for NAD+ and part of the salvage pathway and, as recent research shows, can also influence lifespan when levels are increased in mice. Researchers have recently published the results of a small-scale human trial using the NAD+ precursor NR; however, this study has not yet been subject to peer review and is pending publication in a journal. The NR for the study was supplied by Chromadex, the patent holder and sole producer of Niagen, its particular form of NR; Dr. Charles Brenner, one of the leading study authors, declared that he holds stock in this company. This is not necessarily a red flag, nor does it invalidate the study, but it is something to keep in mind. This study found no correlation between the age of patients and the level of NAD+ in muscle and brain tissue. Therefore, we might not expect age-related changes in these tissues to be reversed due to supplementation of an NAD+ raising supplement, such as nicotinamide riboside. In addition, the study layout was flawed, which may further harm efforts to detect an effect from the supplement. A low number of patients in both treatment and comparison groups, combined with a large range of patient weights (ranging from the lower ‘healthy’ weights to an upper ‘overweight’ limit) and a flawed method of measuring this weight (BMI, which can be distorted by patient height and other factors), reduce the accuracy of any results given in this study. Furthermore, with multiple targets to study, the threshold of certainty below which we could say that the drug is effective is significantly lowered. This was not mentioned by the study authors. | ||
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