X-Message-Number: 20446
From: "michaelprice" <>
References: <>
Subject: warning: accelerated aging by nicotinamide 
Date: Fri, 15 Nov 2002 11:17:51 -0000

The study abstract Doug cites is misleading, taken in isolation.
A little knowledge is dangerous thing....

Nicotinic acid versus nicotinamide (both forms of vitamin B3) is discussed

"Vitamin B3 (niacin) is a precursor to the coenzymes NAD and NAD-phosphate
(NADP).  Although not strictly a vitamin - our bodies can produce NAD/NADP
from dietary tryptophan - it functions like one since this production is not
very efficient.  Dietary consumption of niacin elevates NAD tissue
concentration, in animals and humans[27d, 27e], which up-regulates the
activity of PARP, increasing the DNA repair efficiency and reducing the
induced[27c, 27f] cancer rate and lowering over-all long-term human
mortality[27g].  High PARP activity is associated with longevity in
humans[126d].  Similar cancer prevention, and possibly longevity, is
expected in humans, who are typically more NAD deficient than many

"Vitamin B3 (as nicotinamide) may be toxic in the range 3-6gm/d[85].
Niacin, as nicotinic acid, is generally considered less toxic[40], but,
still, in some individuals large doses of niacin have caused abnormal liver
behaviour.  Also niacin can cause an uncomfortable, although, as far as we
know, harmless and temporary skin flushing.  Taken as inositol
hexanicotinate, which is generally regarded as non-toxic, unlike some other
slow-release formulations[73], removes this problem."

See http://www.longevity-report.com/lr91.htm
for the references and context.

The study Doug cited was also discussed on sci.life-extension a few
months back.  Locate with google using the string: "PMID: 12297502"
or use the URL:

Here was my summary:
My thanks to Lou Pagnucco for bring this study to oiur collective attention.
Having digested the full text version (free on PubMed) I recommend it to
everybody.  It provides a lot of useful background on the relationship
between Sir2, SIRT1/2,  NPT1, p53, NAD+, nicotinic acid, nicotinamide and
the importance of distingishing between the last 3, which hitherto I had
been lax about.  (Niacin is loose term which can mean any of the forms of
vitamin B3.)

High level summary:  nicotinic acid good, nicotinamide/niacinamide bad

One major qualifer is the validity of extrapolating 'aging' in yeast to
multicellular organisms.
It seems that Sir2 extends replicative lifespan in yeast by both decreasing
the formation of ERCs (extrachromosomal rDNA circles) and inhibiting
apoptosis (cell death).  The ERCs are of doubtful relevance to multicellular
eukaryotes such as us who also require apoptosis for tumour suppression;
however mutant Sir2+ nematodes live longer, so perhaps Sir2 is is relevant
to multicellular lifespans.  Also of note is that *nicotinamide* has
extended fruit-fly lifespans.
Michael C Price

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=20446