Flush With Health Success

To what extent is flushing from nicotinic acid/niacin and beta-alanine positively or proportionally related to health?

With a mean follow-up of 15 years, nearly 9 years after termination of the trial, mortality from all causes in each of the drug groups, except for niacin, was similar to that in the placebo group. Mortality in the niacin group was 11% lower than in the placebo group (52.0 versus 58.2%; p = 0.0004). This late benefit of niacin, occurring after discontinuation of the drug, may be a result of a translation into a mortality benefit over subsequent years of the early favorable effect of niacin in decreasing nonfatal reinfarction or a result of the cholesterol-lowering effect of niacin, or both.”

In particular, both the precursor for the coenzyme beta-nicotinamide adenine dinucleotide (NAD(+)), nicotinamide, and the growth factor erythropoietin offer novel platforms for drug discovery that involve cellular metabolic homeostasis and inflammatory cell control. 

More recently, the health benefits of niacin have been shown to be far more extensive than previously appreciated — Numerous reports indicate niacin might help prevent atherosclerosis, diabetes and hypercholesterolemia. Niacin is effective in assisting burn-wound recovery, and in the prevention of cataracts and skin cancer.  


In addition, new NAD+ boosters are welcomed since the side effects of niacin generally lead to poor compliance, despite its known efficacy in a myriad of diseases. Therefore, the dosing and safety of these new NAD+ boosters (e.g. NAD+ precursors, CD38 inhibitors and PARP inhibitors) must be thoroughly assessed to translate these exciting insights into NAD+ biology towards human relevance.

Interestingly, niacin is found in maize but is not bioavailable unless given an alkali treatment, a process used in Aztec and Mesoamerican times termed nixtamalization (Gwirtz and Garcia-Casal, 2014). In animal products, and probably in all uncooked foods, the NAD+ and NADP+ cellular content accounts for much of their dietary niacin content (Gross and Henderson, 1983), yet, as exemplified above with corn nixtamalization, their bioavailability might be affected by food processing or cooking.

However, the clinical use of NA has been limited by the fact that it induces cutaneous flushing, which compromises compliance (Birjmohun et al., 2005). This flushing does not derive from the ability of NA to drive NAD+ synthesis, but rather from the activation of a G-coupled receptor, GPR109A (Benyo et al., 2005).

Alternatively, strong evidence for the ability of NAD+to enhance the activity of sirtuins provides a mechanism of action that also drives benefits on lipid homeostasis (Canto and Auwerx, 2012).

NR was recently demonstrated to have a surprisingly robust effect on systemic metabolism. First, dietary supplementation with NR protected against diet-induced obesity (Canto et al., 2012). NR treatment increased both intracellular and mitochondrial liver NAD+ levels, concomitant to an enhancement of SIRT1 as well as SIRT3 activities (Canto et al., 2012). As a result, there was a SIRT1-dependent increase in FOXO1 deacetylation, along with elevations in SOD2 expression, a FOXO1 target gene.

Maintaining NAD+ levels seems to, hence, sustain basal metabolic function and health in neurons. Furthermore, based on the preliminary evidence above, NR might have a privileged position among different NAD+ precursors in the prevention of neurodegeneration, as the effect of NR may be enhanced by the increase in NRK2 during axonal damage.


  • Adaptive cellular metabolism relies on NAD+ to mediate energy signaling
  • NAD+ therapeutics is showing its potential to treat disease
  • Metabolic syndrome, cancer and aging all involve NAD+ signaling

Many more cherries to pick here but I picked the most edible.


Take it to the bank!

>The problem, Guarente says, is that it’s nearly impossible to prove, in any reasonable time frame, that drugs that extend the lifespan of animals can do the same in people; such an experiment could take decades. That’s why Guarente says he decided to take the unconventional route of packaging cutting-edge lab research as so-called nutraceuticals, which don’t require clinical trials or approval by the FDA.

This means there’s no guarantee that Elysium’s first product, a blue pill called Basis that is going on sale this week, will actually keep you young. The product contains a chemical precursor to nicotinamide adenine dinucleotide, or NAD, a compound that cells use to carry out metabolic reactions like releasing energy from glucose. The compound is believed cause some effects similar to a diet that is severely short on calories—a proven way to make a mouse live longer.

Guarente says Elysium’s pill includes a precursor to NAD, called nicotinamide riboside, which the body can transform into NAD and put to use. In addition, the pill contains pterostilbene, an antioxidant that Guarente says stimulates sirtuins in a different way. Both ingredients can already be found in specialty vitamins.  “We expect a synergistic effect [from] combining them,” he says.



Here is a more direct approach to the title question:


Tangentially, the inflammatory metabolite (related to inflammation which niacin may be protective against) can be measured in sewage to give a marker of community health.

As the company notes. stress-related health factors found to correlate with 8-isoprostane levels can include obesity, cardiovascular disease, diabetes, smoking, cancer, and alcohol consumption.” Thus, it is indeed a useful test for evaluating community health.


Hence, we think that chronically high levels of PGD2 are likely to prevent or reduce the effect of acute signals of PGD2 that would otherwise be anti-inflammatory. See sections on Alzheimer’s disease (AD) below, where chronically high PGD2 signaling is thought to be a major cause of the neurodegenerative features characteristic of AD (Maesaka, 2013).

A very interesting recent paper (Vong, 2010) was published by scientists who believe that the increased expression of prostaglandin D2 synthesis and its EP1 receptor that they detected in individuals in long-term remission from ulcerative colitis suggest that the release of PGD2 in response to acute releases of inflammatory stimuli could be important antiinflammatory protection to maintain colonic mucosal homeostasis.

It appears to us that pulsatile PGD2 release a few times a day with immediate release niacin supplementation may offer better protection against a variety of inflammatory diseases.

PO, hypothetically, if the flush is associated with purging or reducing pre-existing inflammation levels and inflammatory mediators then tolerance or adaptation to a particular dose, less flush with repeated doses, might indicate success.




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