1708 replies to this topic

[tintinet]

A. Makes ya look like ya been nippin' at the bottle!

2. If it progresses to rhinophyma, I'll have to start learning more one liners and enunciating a la W.C. Fields!

[steelheader]

I got a pimple on my butt.

[edward]

lol

[edward]

... back to the everything attributed to resveratrol log

Seroiously though,
Anyone have any clarity on the Niacinamide/Niacin inhibition of SIRT1. I could research it but if anyone has a quick explanation let me know.

[edward]

seriously (spelling) sorry its a pet peeve

[tintinet]

1. Ya can edit yer post ta correct spellin,' if ya wants ta.....(edit here, BTW: Firefox 2.0 and subsequent upgrades have a built in spell checker.)

2. Resveratrol has been found to activate SIRT1 and thus promote longevity, beneficial immune system, metabolic, etc. functions. Nicotinamide has been found to inactivate SIRT1, and thus accelerate aging, etc.....

If it really is that simple, at least.....

[niner]

Anyone have any clarity on the Niacinamide/Niacin inhibition of SIRT1. I could research it but if anyone has a quick explanation let me know.

The story seems to be that niacinamide is the anti-resveratrol, so to speak. Niacin would be the preferred form in that regard. Here's a paper from Sinclair's group.

J Biol Chem. 2002 Nov 22;277(47):45099-107. Epub 2002 Sep 23.  FREE TEXT, Yow!!
Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1.Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA.
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.

The Saccharomyces cerevisiae Sir2 protein is an NAD(+)-dependent histone deacetylase that plays a critical role in transcriptional silencing, genome stability, and longevity. A human homologue of Sir2, SIRT1, regulates the activity of the p53 tumor suppressor and inhibits apoptosis. The Sir2 deacetylation reaction generates two products: O-acetyl-ADP-ribose and nicotinamide, a precursor of nicotinic acid and a form of niacin/vitamin B(3). We show here that nicotinamide strongly inhibits yeast silencing, increases rDNA recombination, and shortens replicative life span to that of a sir2 mutant. Nicotinamide abolishes silencing and leads to an eventual delocalization of Sir2 even in G(1)-arrested cells, demonstrating that silent heterochromatin requires continual Sir2 activity. We show that physiological concentrations of nicotinamide noncompetitively inhibit both Sir2 and SIRT1 in vitro. The degree of inhibition by nicotinamide (IC(50) < 50 microm) is equal to or better than the most effective known synthetic inhibitors of this class of proteins. We propose a model whereby nicotinamide inhibits deacetylation by binding to a conserved pocket adjacent to NAD(+), thereby blocking NAD(+) hydrolysis. We discuss the possibility that nicotinamide is a physiologically relevant regulator of Sir2 enzymes.

PMID: 12297502

[edward]

Ok, time to chuck my multivitamins. So you guys feel Inositol Hexanicotinate and other forms of B3/niacin are ok?

[fearfrost]

Since this is the "500 club" thread, I would just like to say that I am officially part of the 'club'. I was taking 40mg of resv for the past 3 months but just took my first country life dose of 500mg. I will report on any emodin effects or reddening of cheeks or pimples developing in various places...

BTW, I took:
1 g quercetin
5 CL capsules (500mg resv + other various extracts)
2.4 g lecithin
1 alcoholic beverage

[edward]

Anyone know of any Multivitamins that do not contain Niacinamide/Nicotinamide? Besides AOR's $50 a pop... Anyone else worried about this?

[niner]

Spybreak got me thinking about the quercetin issue. Here is one of the papers that he mentioned. In it, we see the claim from the Pisa group that quercetin is a PICOMOLAR(!) inhibitor of resveratrol sulfation. First let me say that a picomolar inhibitor is very unusual. This is three to five orders of magnitude more potent than the typical pharmaceutical. This lab has published several papers on this, but I've not seen it reproduced elsewhere. Various other flavonoids are micromolar inhibitors of the sulfotransferase(s) involved. Unfortunately, I only have the abstract, not the full text (effing journal publishers...) so I don't know if the experimental conditions were such that the quercetin would have been conjugated as it would be in the liver in vivo. If we go on the assumption that the experimental conditions are a satisfactory mimic of in vivo metabolism, then most people with a good diet should have enough quercetin from food sources in their system to inhibit the sulfation of resveratrol. Quercetin has a very long half life (about 24 h). So... did all of the subjects of the resveratrol pharmacokinetics measurements avoid eating apples, onions, broccoli, tea etc for a number of days before the resveratrol challenge? Did De Santi et al. get their setup wrong? I don't know. If the De Santi work is relevant and correct, then a very small amount of quercetin should be enough to improve the bioavailability of resveratrol. The amount needed should be small enough that one need not worry about the weak inhibiting effect of quercetin on SIRT1. On the other hand, you might want to avoid large doses of quercetin, if for no other reason than to avoid inhibiting SIRT1. I pulled a number of factoids used in the concoction of this argument from a great polyphenol review by Claudine Manach, which I've included below.

Xenobiotica. 2000 Sep;30(9):857-66.
Sulphation of resveratrol, a natural compound present in wine, and its inhibition by natural flavonoids.
De Santi C, Pietrabissa A, Spisni R, Mosca F, Pacifici GM.
Department of Neurosciences, Medical School, Pisa, Italy.
1. Resveratrol, a polyphenolic compound present in grape and wine, has beneficial effects against cancer and protective effects on the cardiovascular system. Resveratrol is sulphated, and the hepatic and duodenal sulphation might limit the bioavailability of this compound. The aim of this study was to see whether natural flavonoids present in wine, fruits and vegetables inhibit the sulphation of resveratrol in the human liver and duodenum. 2. In the liver, IC50 for the inhibition of resveratrol sulphation was 12+/-2 pM (quercetin), 1.0+/-0.04 microM (fisetin), 1.4+/-0.1 microM (myricetin), 2.2+/-0.1 microM (kaempferol) and 2.8+/-0.2 microM (apigenin). Similarly, in the duodenum, IC50 was 15+/-2 pM (quercetin), 1.3+/-0.1 microM (apigenin), 1.3+/-0.5 microM (fisetin), 2.3+/-0.1 microM (kaempferol) and 2.5+/-0.3 microM (myricetin). 3. The type of inhibition of quercetin on resveratrol sulphation was studied in three liver samples and was determined to be non-competitive and mixed in nature. Km (mean+/-SD; microM) was 0.23+/-0.07 (control), 0.40+/-0.08 (5 pM quercetin) and 0.56+/-0.09 (10 pM quercetin). Vmax (mean+/-SD; pmol min(-1) x mg(-1)) was 99+/-11 (control), 73+/-15 (5 pM quercetin) and 57 +/- 10 (10 pM quercetin). Kj and Kies estimates (mean+/-SD) were 3.7+/-1.8 pM and 12.1+/-1.7 pM respectively (p = 0.010). 4. Chrysin was a substrate for the sulphotransferase(s) and an assay was developed for measuring the chrysin sulphation rate in human liver. The enzyme followed Michaelis-Menten kinetics and Km and Vmax (mean+/-SD) measured in four livers were 0.29+/-0.07 microM and 43.1+/-1.9 pmol x min(-1) x mg(-1) respectively. 5. Catechin was neither an inhibitor of resveratrol sulphation nor a substrate of sulphotransferase. 6. These results are consistent with the view that many, but not all, flavonoids inhibit the hepatic and duodenal sulphation of resveratrol, and such inhibition might improve the bioavailability of this compound.
PMID: 11055264

From http://www.ajcn.org/...t/full/79/5/727
Flavonols have been more extensively studied. Consumption of these substances has been estimated at 20–25 mg/d in the United States, Denmark, and Holland (67-69). In Italy, consumption ranged from 5 to 125 mg/d, and the mean value was 35 mg/d (70).

Flavonols are the most ubiquitous flavonoids in foods, and the main representatives are quercetin and kaempferol. They are generally present at relatively low concentrations of 15–30 mg/kg fresh wt. The richest sources are onions (up to 1.2 g/kg fresh wt), curly kale, leeks, broccoli, and blueberries (Table 1). Red wine and tea also contain up to 45 mg flavonols/L. These compounds are present in glycosylated forms. The associated sugar moiety is very often glucose or rhamnose, but other sugars may also be involved (eg, galactose, arabinose, xylose, glucuronic acid).

Plasma concentrations reached after polyphenol consumption vary highly according to the nature of the polyphenol and the food source. They are on the order of 0.3–0.75 µmol/L after consumption of 80–100 mg quercetin equivalent administered in the form of apples, onions, or meals rich in plant products (90, 92, 107).

Metabolism of polyphenols occurs via a common pathway (83). The aglycones can be absorbed from the small intestine. However, most polyphenols are present in food in the form of esters, glycosides, or polymers that cannot be absorbed in their native form. These substances must be hydrolyzed by intestinal enzymes or by the colonic microflora before they can be absorbed. When the flora is involved, the efficiency of absorption is often reduced because the flora also degrades the aglycones that it releases and produces various simple aromatic acids in the process. During the course of absorption, polyphenols are conjugated in the small intestine and later in the liver. This process mainly includes methylation, sulfation, and glucuronidation. This is a metabolic detoxication process common to many xenobiotics that restricts their potential toxic effects and facilitates their biliary and urinary elimination by increasing their hydrophilicity. The conjugation mechanisms are highly efficient, and aglycones are generally either absent in blood or present in low concentrations after consumption of nutritional doses. Circulating polyphenols are conjugated derivatives that are extensively bound to albumin. Polyphenols are able to penetrate tissues, particularly those in which they are metabolized, but their ability to accumulate within specific target tissues needs to be further investigated. Polyphenols and their derivatives are eliminated chiefly in urine and bile. Polyphenols are secreted via the biliary route into the duodenum, where they are subjected to the action of bacterial enzymes, especially ß-glucuronidase, in the distal segments of the intestine, after which they may be reabsorbed. This enterohepatic recycling may lead to a longer presence of polyphenols within the body.

[rwoodin]

My throat is still sore and now my eye's seem to be closing everytime I blink!
What have I gotten myself into this time!!
Just kidding and I do think that I picked up something going around here and it likely has nothing to do with the resveratrol. For the chemistrally challenged people such as myself, are you guys saying that B vitamins react with resveratrol? What B vitamins, by number, are you referring to?

[Ghostrider]

Has anyone noticed cognitive decline when taking resveratrol? At first, it was fun and I swear that it gave me energy, but the past few days I have felt about as sharp as a brick and nothing has changed. I have been taking resv at 200 mg for about a week now. Starting to wonder if maybe resv. has bad effects in regards to cognitive performance for me... Does anyone ever feel kinda tired or burnt out after taking high dosage resv. for a week straight?

[steelheader]

"If we go on the assumption that the experimental conditions are a satisfactory mimic of in vivo metabolism, then most people with a good diet should have enough quercetin from food sources in their system to inhibit the sulfation of resveratrol."

Thanks, Niner. Great post.

[edward]

I should have gone to bed hours ago but this niacinamide "the anti resveratrol" issue is driving me nuts. Thanks for the posting the Sinclair stuff. I had stumbled on it. It appears that Niacinamide/Nicotinamide (both the same) not nicotinic acid (which is tradtional niacin but read the find print on bottles, niacinamide is in EVERYTHING). Think of all the recent B vitamin fortified products out there (there are 5 in my kitchen all... yes contain niacinamide as the source for niacin ... after reading the fine print. Personally Quercetin is interesting but as there appears to be benefits in the small doses from everyday food I am content not to supplement it. The niacinamide thing though is disturbing.

Still lookin for the non anti-resveratrol multivitamin...

Edited by edward, 23 March 2007 - 01:26 PM.

[edward]

Maybe I need a rat chow multi ....I'm sure the higher primate chow multi has niacinamide in it.

[health_nutty]

I should have gone to bed hours ago but this niacinamide "the anti resveratrol"  issue i driving me nuts. Thanks for the posting the Sinclair stuff. I had stumbled on it. It appears that Niacinamide/Nicotinamide (both the same) not nicotinic acid (which is tradtional niacin but read the find print on bottles, niacinamide is in EVERYTHING). Think of all the recent B vitamin fortified products out there (there are 5 in my kitchen all... yes contain niacinamide as the source for niacin ... after reading the fine print. Personally Quercetin is interesting but as there appears to be benefits in the small doses from everyday food I am content not to supplement it. The niacinamide thing though is disturbing.

Still lookin for the non anti-resveratrol multivitamin...

This was me one month ago.
Super Premium: Orthocore (too expensive for me)
Midgrade: SuperNutritionUSA Perfect Blend (my choice)

It's niacinamide, bioprene, and iron free.

[tintinet]

Ya can get LEF mix without niacinamide and with or without niacin, as well as other variations. NSI, AFAIK, at least in some of their formulations, includes niacinamide....

[niteinnyc]

I should have gone to bed hours ago but this niacinamide "the anti resveratrol"  issue i driving me nuts.

Still lookin for the non anti-resveratrol multivitamin...

If you want just a B-complex there is Country Life's Coenzyme B-Complex.

http://country-life....198#Ingredients

[maxwatt]

Maybe I need a rat chow multi ....I'm sure the higher primate chow multi has niacinamide in it.

Labdiet 5048 large primate chow:
http://www.labdiet.c...labdiethome.htm

It has 103 ppm niacin, which is a dietary amount rather than a pharmacological amount.
I rather think a modest amount of Niacin, will not significantly activity or resveratrol. FWIW, I rather think most people do not benefit from supplementing much above the RDA for most B vitamins (exceptions being B12, folic acid and Biotin). They are co-factors; beyond a certain amount, at best they don't do anything for you. There are people of northern European extraction who have genetic abnormalities such that they require mega-amounts of some B vitamins, but if that is not you, there is no benefit.

Edited by maxwatt, 23 March 2007 - 11:59 AM.

[edward]

Thanks guys.

health nutty, you saved me a lot of frustration. SuperNutritionUSA Perfect Blend looks good. Interestingly their Super Blend has niacinamide but the Perfect Blend is as you said Niacinamide, Bioperine and Iron free... Hopefully no one decides its ok to throw in niacinamide instead of niacin in the next batch since they have both laying around... ha ha

[fearfrost]

After taking 500mg of resveratrol via Country life, I felt nothing. No explosive bowel movements, no gas, nothing. And all this time I was worried about emodin...

[maxwatt]

After taking 500mg of resveratrol via Country life, I felt nothing.  No explosive bowel movements, no gas, nothing.  And all this time I was worried about emodin...

Sometimes it takes a while to kick in. Some people have no problem. Try three capsules, = 750 mg of resv.

[health_nutty]

Thanks guys.

health nutty, you saved me a lot of frustration. SuperNutritionUSA Perfect Blend looks good. Interestingly their Super Blend has niacinamide but the Perfect Blend is as you said Niacinamide, Bioperine and Iron free... Hopefully no one decides its ok to throw in niacinamide instead of niacin in the next batch since they have both laying around... ha ha

No problem, they have both an iron and iron free version so make sure you are getting the right one.

[peakbagger]

First time poster -- age 52, 6'0", 175 lbs, BP 115/70, heart rate 51 bpm -- I exercise approx 5 times a week, mixing it up with martial arts, weight lifting/general fitness, yoga, elliptical, rowing, and static and dynamic stretching plus I play disc golf and golf. I have 3 grandparents that lived into their 90s and the 4th died from a heart attack at 65 but his sister lived to be 100. People never believe me when I tell them my age.

I take a lot of supplements and have done so for 25 years. These days, I take the top 5 LEF suggestions (Mix, Booster, CoQ10, Mitochodrial, and EFAs) plus a myriad of extracts and powerfoods like whey protein, defatted wheat germ, flax meal, super greens powders. I eat lots of vegetables and for the most part, don't eat processed foods -- I aslo eat meat/fish/poultry but in small portions (4-6 oz).

So I decided to up my dose of 50 mg resveratrol and bought the LEF 100mg capsules (which I know is relatively expensive but I know I am getting quality). Ambitiously, I ramped up to approx 500 mg within a week and it definitely had an effect on me but not the same as has been reported by most. I felt wired and almost light-headed -- it wasn't particularly comfortable. I seemed to wake up earlier and did not sleep as soundly throughtout the night but didn't feel run down or tired during the day. It probably did not help that I continued with my coffee drinking.

Anyway, I backed down to approx 200 mg and that puts me into a range that still feels a little wired and my sleep is still diminished but it's not uncomfortable. After a period of acclimatization, I may try boosting to 300 mg.

[health_nutty]

First time poster -- age 52, 6'0", 175 lbs, BP 115/70, heart rate 51 bpm -- I exercise approx 5 times a week, mixing it up with martial arts, weight lifting/general fitness, yoga, elliptical, rowing, and static and dynamic stretching plus I play disc golf and golf.  I have 3 grandparents that lived into their 90s and the 4th died from a heart attack at 65 but his sister lived to be 100.  People never believe me when I tell them my age.

Interesting! Thanks for sharing your experience. It's encouraging to hear what a healthy diet/exercise and supplementation program can do.

[health_nutty]

Thanks guys.

health nutty, you saved me a lot of frustration. SuperNutritionUSA Perfect Blend looks good. Interestingly their Super Blend has niacinamide but the Perfect Blend is as you said Niacinamide, Bioperine and Iron free... Hopefully no one decides its ok to throw in niacinamide instead of niacin in the next batch since they have both laying around... ha ha

I emailed SupernutritionUSA to confirm the form of B-3 they use in the Perfect Blend. Here the reply:

"Two-stage, fast-release niacin refers to regular niacin that has been coated in vegetable protein so
as to release in stages and lowers the possibility of flushing"

Excellent

[rwoodin]

Ambitiously, I ramped up to approx 500 mg within a week and it definitely had an effect on me but not the same as has been reported by most.  I felt wired and almost light-headed -- it wasn't particularly comfortable.

peakbagger - I felt very much like you describe. It was mood elevating at first but after a while it became to much to be comfortable with. I enjoy feeling relaxed, not stressed out. I'm backing off to between 100-200mg for now

[krillin]

Anyone know of any Multivitamins that do not contain Niacinamide/Nicotinamide? Besides AOR's $50 a pop... Anyone else worried about this?

I'm taking the AOR Multi-Basics 3 now, but will move up to Ortho-Core as Unique Nutrition is selling it for only $34.99 a bottle.

[niner]

...will move up to Ortho-Core as Unique Nutrition is selling it for only $34.99 a bottle.

That's a damn good price. It's also sold out. I noticed they also had R(+)SR (AOR's time release lipoic acid) for $29.99, also a great price. I wonder what the story is on cost, profit margin, and reliability at U.N?