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Niacinamide and SIRT - what is the minimum dose required for inhibition?


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#1 agwoodliffe

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Posted 15 July 2012 - 10:24 PM


I have become very confused about the use of Niacinamide in place of Nicotinic acid for supplementing. Numerous studies have documented that Niacinamide/Nicotinamide acts as an inhibitor of the 'Sirtuin' proteins, in the opposite manner of Resveratrol, and hence eliminating Resveratrol's possible effects on lifespan. The doses of Niacinamide typically found in multivitamins / B-complex vitamins, typically range from 20mg - 100mg.

My query is, what is the minimal dosage required to achieve this effect?

(According to Pubchem, the concentration required for 50% inhibition of SIRT2 is 11uM, although I have no idea how this translates to mg/kg)

#2 maxwatt

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Posted 16 July 2012 - 02:53 PM

I suspect you will be able to attain such a blood level but briefly, if at all, from oral dosing. The amount in a typical B vitamin should be nothing to worry about.

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#3 tham

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Posted 16 July 2012 - 07:07 PM

Upregulation of SIRT1 may increase lifespan in fruit flies and roundworms, but
may actually have detrimental effects in strokes, some types of cancer and dementia,
particularly when NAD+ levels are insufficient.

The types of cancer in question apparently include prostate cancer and SCLC.

http://www.ncbi.nlm....68412, 18402819


The anticancer protocol which the late Abram Hoffer faxed me 16 years ago
included 1,500 mg of niacinamide.

Inhibition of SIRT1 is apparently one of the pathways in which niacinamide fights cancer.

If you look at the first study in the Medline search above :

" Stroke resulted in dynamic changes of SIRT1 protein and activity levels which varied
among brain regions. Administration of nicotinamide (200 mg/kg, i.p.) up to 1 hour after
the onset of ischemia elevated brain NAD(+) levels and reduced ischemic infarct size."

200 mg/kg in mice = 200 x 60 / 12 = 1,000 mg in a 60 kg human being.




Furthermore, in the same study :

" Studies of yeast and cultured mammalian cells indicate that Sir2/SIRT1 can increase
replicative lifespan and cellular stress resistance (Blander and Guarente 2004), but may
reduce the chronological lifespan of cells under certain conditions (Fabrizio et al. 2005).
Previous findings concerning the influence of SIRT1 on neuronal stress resistance and
survival are conflicting. SIRT1 activity plays an important role in maintaining the viability
of at least some types of cells because most SIRT1 null mice die during the postnatal
period and exhibit retardation in growth and defects in development (McBurney et al. 2003).

SIRT1 deacetylase activity is dependent upon NAD+, and NAD+ depletion during
excitotoxic and ischemic conditions would therefore be expected to decrease SIRT1 activity
(Yang and Sauve 2006), although SIRT1 activity may not be affected by NAD+ fluctuations
within the physiological range (Anderson et al. 2003). Our findings suggest that SIRT1
levels and activity in neurons are influenced by cellular NAD+ levels, and that nicotinamide
treatment attenuates depletion of NAD+ and preserves SIRT1 activity in neurons under
excitotoxic and ischemic conditions. "

" While SIRT1 may play a role in maintaining cell viability under conditions of sufficient
energy availability, we found that the SIRT1-activating agent resveratrol could not rescue
neurons under excitotoxic conditions, and even exacerbated excitotoxic neuronal death at
higher concentrations
(data not shown). Similar death-promoting effects of resveratrol and
SIRT1 have been observed in models of zinc-induced cytotoxicity.

The latter finding is of interest because zinc is released from excitatory synapses and
may contribute to excitotoxicity and neuronal death following ischemia. "


" Other studies show that resveratrol can promote apoptosis of tumor cells and some types
of normal mitotic cells (Clement et al. 1998; Gao et al. 2002). Consistent with our findings,
a recent study showed that heart-specific overexpression of SIRT1 increases the
vulnerability of cardiac myocytes to age-dependent apoptosis, whereas lower levels of
SIRT1 overexpression were protective
, possibly by activating an adaptive stress response
pathway (Alcendor et al. 2007). We found that the SIRT1 inhibitors nicotinamide and sirtinol
protected neurons against excitotoxicity, a finding consistent with previous data
demonstrating neuroprotective effects of sirtuin inhibitors in models of Alzheimer's and
Huntington's diseases (Green et al. 2008; Butler and Bates 2006). Pretreatment with
resveratrol has been reported to protect neurons against ischemic cell death, apparently
by inducing an adaptive stress response (Raval et al. 2006). "

" Our findings suggest that SIRT1 may promote cell survival and be involved in adaptive
stress responses under conditions where cells have sufficient NAD+; however, when
NAD+ levels are limited, stimulating SIRT1 activity may render cells vulnerable to death
. "

" The neuroprotective effects of nicotinamide appear to result from both elevation
of NAD+ levels and sirtuin inhibition
. "


http://www.ncbi.nlm....cles/PMC2677622



Sir2-Independent Life Span Extension by Calorie Restriction in Yeast

http://www.plosbiolo...al.pbio.0020296



Sir2 blocks extreme life-span extension.

http://seroudelab.bi...f/fabrizio2.pdf

#4 pamojja

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Posted 16 July 2012 - 07:15 PM

The anticancer protocol which the late Abram Hoffer faxed me 16 years ago included 1,500 mg of niacinamide.


Interesting. What else did he recommend?

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#5 timhill88@outlook.com

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Posted 14 December 2014 - 03:33 PM

Hi Does

Niacinamide increase Histamine becuase I have anxiety and panic attack disorder when I have Niacinamide I get more anxiety
 




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