Niacin and Sirt expression, longevity, etc.

[Guest guest]

Hi all, I'm new here and still learning.

My question relates to Niacin (nicotinic acid) at pharmacologic

doses, which I take along with Lipitor and Zetia to control Type IIA

hypercholesterolemia. I also practice CRON. I came across work on

niacinamide and nicotinic acid and their relationship to Sirt1

expression. The articles are confusing as to what effect taking

niacin may have on the Sirt pathway and biomarkers of longevity. I

have good medical and biochemical knowledge, and have read many of

the abstracts and some ot the full text articles, but there are no

statements I can find directly addressing niacin or niacin

supplementation in humans or mammals with respect to Sirt effects .

I am well aware of the effects of niacin on lipid metabolism, LDL,

HDL, and heart disease risk (all favorable), but the interaction

with Sirt is confusing to me (maybe unfavorable?). The work from

Sinclair etc. was done in yeasts, where it appears a deficit of

nicotinamide (niacinamide) increases Sirt expression. Niacinamide

is the biochemical precursor of nicotinic acid (niacin). The

article in Nature (Sinclair) states exogenous nicotinic acid in

vitro did not increase rDNA silencing, but I don't think it said it

decreased it either. I understand feedback mechanisms in general but

it is not clear to me what effect nicotinic acid supplementation

would have in vivo on niacinamide levels and Sirt. Here are some

abstacts or links, which if you are like me, you may also find

confusing when comparing the statements made in each. I have a pdf

of the Sinclair/Nature article if anyone wants it.

1. Cell Life versus cell longevity: the mysteries surrounding the

NAD+ precursor nicotinamide.

Curr Med Chem. 2006;13(8):883-95. Review.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=16611073 & query_hl=2 & it

ool=pubmed_docsum

2. Navigating novel mechanisms of cellular plasticity with the NAD+

precursor and nutrient nicotinamide.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=15353303 & query_hl=2 & it

ool=pubmed_docsum

3. Nicotinamide and PNC1 govern lifespan extension by calorie

restriction in Saccharomyces cerevisiae.(This article states: " We

provide evidence that nicotinamide depletion is sufficient to

activate Sir2 and that this is the mechanism by which PNC1 regulates

longevity. "

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=15353303 & query_hl=2 & it

ool=pubmed_docsum

4. This pdr health description of niacin includes this statement,

but it refers to NAD but not niacin.

" Recently, it has been found that NAD+ plays a key role in life-span

extension by calorie restriction in the yeast Saccharomyces

cerevisiae. It does so by serving as the cofactor for an NAD+-

dependent histone deacetylase, an enzyme that removes acetyl groups

from the lysine residues of histone proteins, thus promoting genomic

silencing. Maintenance of genomic silencing may be critical to

longevity either by repressing genomic instability or by preventing

inappropriate gene expression. A similar mechanism may operate in

metazoans, including humans "

http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/nia_018

4.shtml

If anyone has any further insight as to what effect exogenous niacin

may have on Sirt in vivo in mammals, or if this has been addressed

previously on the list, I would be most interested in learning

more. Thanks.