82 replies to this topic

[ageless]

Back to quercetin...

In reference to fearfrost's posted regimine with quercetin:

I agree with health nutty that that seems like a lot of quercetin, simply because if it is not stabilized it has been shown to inhibit SIRT and I wouldn't want that kind of resveratrol to quercetin ratio (activator to potential inhibitor). I don't want to destroy the positives of my Resveratrol supplementation by being overzealous with a potential synergist. I'm leaning towards AOR's ratio of 2 to 1 as in two parts Resveratrol to one part Quercetin (or less) with a good dose of vitamin c.

I haven't added quercetin as a part of my daily Resveratrol stack, though when I have tried the two together I do get a greater subjective effect and I am finally being convinced by what I have read that adding it would be a good thing. So I am thinking about adding it at a ratio of 2 to 1 or less.

So possibly with my AM and PM dosing of Resveratrol  at 400mg adding 200mg quercetin with 800 mg Vit C

What do other people think? What dosages of quercetin with Resveratrol is everyone taking?

I am taking the AOR product. Trust me, (read my last few posts in the 500mg club thread,) the quercitin/luteolin/piperine mix definitely was inhibiting my P450 'zimes, just as intended. Hopefully it is increasing my free t-res levels as well.

I can happily report that today I took my Paxil 8 hours after my morning does of AOR acta-tres, and I had no problems.

Good to hear. Sounds like a smart move. I'm liking my Acta-resveratrol.

[opales]

I am taking the AOR product. Trust me, (read my last few posts in the 500mg club thread,) the quercitin/luteolin/piperine mix definitely was inhibiting my P450 'zimes, just as intended. Hopefully it is increasing my free t-res levels as well.

I can happily report that today I took my Paxil 8 hours after my morning does of AOR acta-tres, and I had no problems.

Do you have information about the timecourse of cyp enzyme inhibition, eight hours does not seem that much?

For example, grapefuit juice can inhibit cyp 3A4 substantially up to three days (sic!). The effect is of course drug dependent (+I was under the impression grapefruit inhibits mostly intestinal cyp) but for example concominant ingestion of grapefruit and simvastatin increased simvastatin peak concentration (Cmax) and area under curve (AUC) 12 and 13.5 fold compared to no grapefruit juice (!!!!!!), respectively, whereas the numbers were 2.4 and 2.1 when ingesting simvastatin 24hrs after grapefruit juice and 1.5 and 1.4 when ingesting simvastatin 3 days after grapefruit juice.

http://www.powernetd.../mechanism.html

I would imagine the timecourse of the recovery would be more dependent on the inhibited enzymes themselves rather the substance inhibiting.

[sUper GeNius]

I am taking the AOR product. Trust me, (read my last few posts in the 500mg club thread,) the quercitin/luteolin/piperine mix definitely was inhibiting my P450 'zimes, just as intended. Hopefully it is increasing my free t-res levels as well.

I can happily report that today I took my Paxil 8 hours after my morning does of AOR acta-tres, and I had no problems.

Do you have information about the timecourse of cyp enzyme inhibition, eight hours does not seem that much?

For example, grapefuit juice can inhibit cyp 3A4 substantially up to three days (sic!). The effect is of course drug dependent (+I was under the impression grapefruit inhibits mostly intestinal cyp) but for example concominant ingestion of grapefruit and simvastatin increased simvastatin peak concentration (Cmax) and area under curve (AUC) 12 and 13.5 fold compared to grapefruit juice (!!!!!!), respectively, whereas the numbers were 2.4 and 2.1 when ingesting simvastatin 24hrs after grapefruit juice and 1.5 and 1.4 when ingesting simvastatin 3 days after grapefruit juice.

http://www.powernetd.../mechanism.html

I would imagine the timecourse of the recovery would be more dependent on the inhibited enzymes themselves rather the substance inhibiting.

I really don't know the answer to your questions. I did read that there are at least two enzymes responsible for Paxil's metabolism. The first enzyme needs to be first saturated, then the second comes into play. Perhaps I am feeling better because my I have adjusted and am now producing more of the second tier enzyme.

The other thing to keep in mind is the non-linear effects of Paxil. The effects are linear with dose, but just up to the point of the first tier enzyme being saturated. Read this in Paxil's prescribing information. Perhaps I had been near saturation, and then a few days ago went past the first tier saturation point?

I am really not medically qualified to explain the effects of the last few days, I can only relay them. For now on I will be taking the t-res in the morning, and the Paxil in the early evening.

[mirian]

Edward don't waste your money on ascorbate C or Ester-C. Here's why:

Taking 500mg of ascorbate is like taking 250mg of ascorbic acid:

"He explains that each molecule of ascorbic acid reacts with two free electrons or "free radicals." Mineral ascorbates, already bound to the mineral ion, react only with one free radical per molecule. This means, literally, that twice as much vitamin C in the form of mineral ascorbates is necessary for positive therapeutic results":

http://www.emediawir...1/emw200561.htm

Just buy cheap 500mg ascorbic acid capsules with 350mg or more of bioflavonoids for every 500mg of ascorbic acid. Only $4.29 for 250 Caps & GMP certified:

http://www.swansonvi...CatalogId=10051


500mg every 3 waking hours making 5 times daily in divided doses is ideal:

"Protective effects of Quercetin and Vitamin C against Oxidative Stress-Induced Neurodegeneration."[Journal Agric Food Chem 52: 7514-17, 2004]

Dr. Nicholas Perricone recommends 1,000mg to 3,000mg of vitamin C daily in his new book 7 steps to longevity. He cites a study in his book showing that people taking 1,500mg of vitamin C before or after a excercising recovered faster than those taking placebo !

"The Common Cold: Outdated advice when you have a cold, loading up on vitamin C supplements will help you get over it faster. New thinking vitamin C doesn't seem to do the job once symptoms have set in, according to a major review of 29 studies from Australian National University. One study suggest taking 500mg daily year-round may prevent colds." [Prevention Magazine, Oct. 2006, p.137]

Normally, vitamin C increases absorption of iron from foods, so 500mg ascorbic acid Vcaps should always contain at least 350mg of bioflavonoids(Vitamin P). Bioflavonoids are iron-binding antioxidants and thus counter this problem. [Biology Trace Element Research 62: 135-53, 1998]

100mg of bioflavonoids that contain red and purple pigments improve capillary closure nearly eight times better than bioflavonoids derived from citrus fruit.[The Parmacology of Plan Phenolics, J.W. Fairbairn, ed., Academic Press, pp.81-90, 1959]

"C THE END OF ULCERS. Those with the highest levels of vitamin C were the least likely to show evidence of H.pylori infection."[Mens Health Magazine, May 2005, p.129]

Quercetin inhibits cold viruses, poliovirus, flu virus, respiratory virus, herpes simplex virus, and SARS virus.[J Med Virology 15:71-79, 1985; Pharmazie 55:129-32, 2000]

Quercetin blocks many of the enzymes that degrade collagen.[Mutation Research 481: 269-276, 2001]

QUERCETIN IS AN EXCELLENT COMPANION OF VITAMIN C. [AM J CLIN NUT 67:1210-18,1998]

70% OR MORE OF THE AMOUNT OF VITAMIN C TAKEN MUST BE IN BIOFLAVONOIDS.[J AM DIETETIC AASN. 94:779-81,1994]

500mg of vitamin C taken orally in 5 divided doses every three waking hours daily (2,500mg total per day) could reduce cardiovascular mortality risk by 55%. Compared to people consuming low doses of vitamin C.[The Science of Vitamin C Book, 2004]

"Megadoses of vitamin C wash out B12 and folic acid; so be sure you are taking at least the daily requirement of both." [Earl Mindell's Vitamin Bible For The 21st Century Book, 1999, p.384]

ESTERFIED C MAY YIELD HIGHER BLOOD LEVELS OF THIS VITAMIN, BUT TWO HOURS AFTER CONSUMPTION THERE WAS LITTLE DIFFERENCE IN BLOOD LEVELS OF PLAIN ASCORBIC ACID AND ESTERFIED C.[J OPTIMAL NUTRITION 2:205,1993]

TAKING 500MG OF VITAMIN C DAILY MAY LOWER YOUR RISK OF CATCHING A COLD BY 66%.[MENS HEALTH MAGAZINE,OCT. 2006, P.48]

500MG DAILY OF VITAMIN C CAN REDUCE CARDIAC CRP BY 24%[MENS HEALTH MAGAZINE,FEB.2006,P.117]

"THE AB'S VITAMIN. PEOPLE WHO TAKE 500MG OF VITAMIN C DAILY BURN 39% MORE FAT DURING EXERCISE."[MENS HEALTH MAGAZINE, APR. 2006, P.52]


VITAMIN C UP TO 3,000MG DAILY IS SAFE. MORE THAN 500MG IN A SINGLE DOSE IS NOT WELL ABSORBED.[PDRHEALTH.COM]:

http://www.pdrhealth.../vit_0264.shtml


EVEN IN HEALTHY INDIVIDUALS, 500-3,000MG OF VITAMIN C IMPROVES WOUND HEALING.[ORAL SURG MED PATHOLOGY 53:231-36, 1982]

[mirian]

Flax oil is prone rancidity, so that why I always only get softgels not the bottled oil that needs refrigeration.

Jarrow's DHA fish oil clearly says, "Preferably store in refrigerator" on its label, so fish oil has issues as well:

http://www.jarrow.co...t.php?prodid=91

Fish oil almost always gives nasty fish burps unless they used flavoring which is usually lemon or strawberry.

Edited by mirian, 19 July 2007 - 11:03 PM.

[krillin]

Edward don't waste your money on ascorbate C or Ester-C. Here's why:

Taking 500mg of ascorbate is like taking 250mg of ascorbic acid:

"He explains that each molecule of ascorbic acid reacts with two free electrons or "free radicals." Mineral ascorbates, already bound to the mineral ion, react only with one free radical per molecule. This means, literally, that twice as much vitamin C in the form of mineral ascorbates is necessary for positive therapeutic results":

Ascorbates and ascorbic acid are interchangeable, unless you're concerned about stomach acidity. Ascorbic acid becomes ascorbate under physiologic pH and mineral ascorbates dissociate in solution.

[Brainbox]

Dr. Nicholas Perricone recommends 1,000mg to 3,000mg of vitamin C daily in his new book 7 steps to longevity. He cites a study in his book showing that people taking 1,500mg of vitamin C before or after a excercising recovered faster than those taking placebo !

From the ever exiting world of research:

Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process.Close GL, Ashton T, Cable T, Doran D, Holloway C, McArdle F, MacLaren DP.
Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK. gclose@liv.ac.uk

Exercise involving lengthening muscle actions, such as downhill running, results in delayed onset muscle soreness (DOMS), which may be attributable to reactive oxygen species (ROS). Although exercise causes oxidative stress, any link between ROS and DOMS remains speculative. There is emerging evidence to suggest that ROS play an important physiological role, assisting in the recovery process and protecting the cell from future damage; however, this has not been fully established. Despite this uncertainty as to the precise role of ROS, attempts to prevent post-exercise ROS production through antioxidant intervention are still common. The study investigated the effects of ascorbic acid supplementation on ROS production and DOMS following downhill running. Subjects were assigned to two groups. The ascorbic acid group (group AA) received 1 g ascorbic acid 2 h pre-, and for 14 d post-downhill running, whilst the placebo group (Pl group) received a placebo. Blood samples were drawn pre-supplement, pre- and post-exercise, and then 1, 2, 3, 4, 7 and 14 d post-exercise for analysis of ascorbate, malonaldehyde and total glutathione. DOMS was assessed using a visual analogue scale and pressure algometry. Muscle function was assessed using isokinetic dynamometry. Plasma ascorbate was elevated throughout in group AA compared with the Pl group. Downhill running resulted in DOMS in both groups. Muscle function was impaired post-exercise in both groups, although a delayed recovery was noted in group AA. Malonaldehyde increased 4 d post-exercise in the Pl group only. Ascorbic acid supplementation attenuates ROS production following downhill running, without affecting DOMS. Furthermore, ascorbic acid supplementation may inhibit the recovery of muscle function.

PMID: 16611389 [PubMed - indexed for MEDLINE]

[mirian]

All the studies talking any smack about Vitamin C are flawed from their inception because you have to use 70% of the amount of vitamin C as vitamin P! A Journal has already stated this.

Vitamin P also known as bioflavonoids. Quercetin being the most powerful bioflavonoid at about 10,000 ORAC per 1,000 mg. Compared to ascorbic acid at about 2,000 ORAC per 1,000 mg.

It's my opinion, that trans resveratrol has such a great effect on such small amounts in red wine is because of the quercetin with it naturally.

I think these studies on resveratrol could drop the dosage and throw in some quercetin and have the same effect.

The argument that quercetin is added with resveratrol because it's cheaper is a far reach quercetin is not a cheap supplement either.

I'd recommend either Jarrow Quercetin 500 mg capules or for a slightly cheaper deal NOW foods 500 mg in Veggie Caps both are at Iherb. Not sure about Jarrow but NOW is labeled citrus free plus with NOW you get Veggie caps for free.

[krillin]

All the studies talking any smack about Vitamin C are flawed from their inception because you have to use 70% of the amount of vitamin C as vitamin P! A Journal has already stated this.

In the past you've used PMID 8021423 as the source for the 70% claim. Unfortunately there is no abstract available. This article summarizes the results as

Nine people were involved in a double blind study in which they took 500 mg of the ascorbic acid form of vitamin C, 500 mg of ester-C, 500 mg of ascorbic acid with bioflavonoids, or a placebo. The authors concluded after comparing plasma levels, urinary excretion rates, and vitamin C retention that there was no difference between these supplements. The authors recommended the utilization of ascorbic acid vitamin C because it was much less expensive than vitamin C with bioflavonoids or ester-C.

Do you have any other evidence to support your 70% claim?

Edit to add:

This article uses your reference to support their conclusion that

Although many bioflavonoids are thought to function as antioxidants, there is little evidence that the bioflavonoids in most commercial preparations increase the bioavailability or efficacy of vitamin C.

Thus, you appear to have been fooled by someone again. Was it Men's Health or was it Prevention?

Edited by krillin, 20 July 2007 - 12:54 AM.

[mirian]

Andrew Weil usually writes the monthly articles for prevention magazine and trust me you're no Dr. Weil.

Stop making fun of people who get paid to make important decisions.

70% or more of the amount of vitamin C taken must be in bioflavonoids. [J AM DIETETIC AASN. 94:779-81,1994]

Taking vitamin C without enough Vitamin P means you're just pissing your money away, literally.

[maxwatt]

Andrew Weil usually writes the monthly articles for prevention magazine and trust me you're no Dr. Weil.

Stop making fun of people who get paid to make important decisions.

70% or more of the amount of vitamin C taken must be in bioflavonoids. [J AM DIETETIC AASN. 94:779-81,1994]

Taking vitamin C without enough Vitamin P means you're just pissing your money away, literally.

This is an example of an "argument from authority", which works for the Pope, but has no place in scientific discourse. Either bioflavonoids are needed to make use of vitamin C, or they aren't. The weight of evidence Krillen posted seems to belie what you believe to be Dr. Weils claim that they are.

[krillin]

Andrew Weil usually writes the monthly articles for prevention magazine and trust me you're no Dr. Weil.

I read a Prevention issue recently in a doctor's office. It said that fish oil rancidity was harmless, other than causing fish burps.

70% or more of the amount of vitamin C taken must be in bioflavonoids. [J AM DIETETIC AASN. 94:779-81,1994]

That is PMID 8021423. Two independent sources summarized the results as bioflavonoids having no effect on C absorption or retention. Have you actually read the paper? If so, what was the difference between taking C with or without the bioflavonoids?

[neogenic]

Bump for this thread. I'd love to hear more on the quercetin/resveratrol combo that is everywhere now. Does this mean taking pure trans-resveratrol could be less effective than taking red wine or a mixed isomer res + quercetin?

[maxwatt]

Bump for this thread.  I'd love to hear more on the quercetin/resveratrol combo that is everywhere now.  Does this mean taking pure trans-resveratrol could be less effective than taking red wine or a mixed isomer res + quercetin?

OK; there has been some discussion of quercetin in other resveratrol threads; a partial summary: Quercetin is sulfonated big-time, and apparently spares resveratrol both in the intestines and in the liver. Biperin (piperidine, from black pepper) is glucoronated to a higher egree than quercetin, and is also used in conjunction with quercetin to improve resveratrol's bioavailability. However, a quercetin metabolite inhibits SIRT1. The question is whether the greater bioavailabiliy of resveratrol is outweighed by this inhibition. Though resveratrol serum levels may be higher with quercetin in the mix, it ma no longer activate SIRT1 due to inhibitin by this metabolite. I believe this is the case, having tried adding quercetin to my regimen: the COX2 effects (reduction of inflamation) were greater, but the deep long term pain from arthritis becam worse within three days (SIRT1 mediates inhibition of NF Kappa, which improves arthritis symptoms.)

Other flavones are sulfonated as strongly as quercetin, and may not inhibit SIRT1. I think they are worth exploring. Chrysin is one, though it is poorly absorbed from the intestines (due perhaps to sulfonation in the intestines.)

See THIS PAPER. and (SEE TABLE)

[platypus]

Quercetin is sulfonated big-time, and apparently spares resveratrol both in the intestines and in the liver.  Biperin (piperidine, from black pepper) is glucoronated to a higher egree than quercetin, and is also used in conjunction with quercetin to improve resveratrol's bioavailability.  However, a quercetin metabolite inhibits SIRT1.

It seems quercetin is a major component of the greenness of green tea:
http://www.blackwell....2004.tb09894.x
Powdered Matcha makes a very very green tea, are here any implications for the normal consumer?

[neogenic]

So, I looked at the table and Luteolin stands out. Isn't that in AOR's formula?

I found this in some digging, not sure if they are in your table:

Title: Tissue distribution in mice and metabolism in murine and human liver of apigenin and tricin, flavones with putative cancer chemopreventive properties

Authors: Cai, Hong; Boocock, David J.; Steward, William P.; Gescher, Andreas J.

Abstract: Purpose: The flavones apigenin and tricin, which occur in leafy vegetables and rice bran, respectively, possess cancer chemopreventive properties in preclinical rodent models. Their pharmacology is only poorly understood. We compared their tissue levels in mice in vivo and their metabolism in liver fractions in vitro. Methods: Mice received apigenin or tricin (0.2%) with their diet for 5-7 days, and flavone levels were compared in the plasma, liver and gastrointestinal mucosa using HPLC-UV. Flavone metabolism was investigated in murine and human liver microsomes or cytosol in vitro co-incubated with uridine 5’-diphosphoglucuronic acid or 3’-phosphoadenosine-5’ phosphosulfate. Flavone metabolites were characterized by on-line HPLC-mass spectrometry. Results: After dietary administration of flavones for 7 days, levels of tricin in plasma, liver and mucosa exceeded those of apigenin by 350, 33 and 100 %, respectively. Apigenin was more rapidly glucuronidated than tricin in liver microsomes, whilst tricin underwent swifter sulfonation than apigenin in liver cytosol. For either flavone the rate of glucuronidation was much faster than that of sulfonation. Flavone monoglucuronides and monosulfates were identified as metabolites in microsomal and cytosolic incubations, respectively. Conclusions: When consumed with the diet in mice tricin seems to be more available than apigenin in blood and tissues. Differences in their glucuronidation may account for their differential availability. Thus tricin may have a pharmacokinetic advantage over apigenin. This type of information may help decide which flavonoids to select for clinical development.

[neogenic]

http://www.scielo.cl...ipt=sci_arttext
This study looks at flavones and their health benefit, as well as breaking down content in food and beverage. Of all wines, Cab. Sav. is a standout. And, interestingly, celery hearts have twice the content of the stalks.

[kenj]

Though resveratrol serum levels may be higher with quercetin in the mix, it ma no longer activate SIRT1 due to inhibitin by this metabolite. I believe this is the case, having tried adding quercetin to my regimen: the COX2 effects (reduction of inflamation) were greater, but the deep long term pain from arthritis becam worse within three days (SIRT1 mediates inhibition of NF Kappa, which improves arthritis symptoms.)

How much quercetin were you taking?

[trh001]

Hi

I  posted the following to the resveratrol users group at yahoo, but it's relevant to this thread if we substitute "Green Tea" for "quercetin:"

My question is this: Are green tea supplements working at cross-purposes to resveratrol supplements? It appears from the [study cited at the top of this thread] that "under stabilizing conditions" EGCg stimulated Sirt1, but "strongly inhibited" it when those "conditions" were not met.

Does one have to choose between resveratrol and EGCg? That would suck. And what is meant by "stabilizing conditions?" Is "stabilized" EGCg available on the market? I'd appreciate any thoughts on this.

And while we're on the subject of green tea, it looks like we should be snorting
it. No joke:

http://www.scienceda...61230110309.htm

"3.2. Polyphenols influence recombinant SIRT1 activity directly and indirectly

To determine the effects of polyphenols on SIRT1 deacetylase activity, we used the recombinant SIRT1 protein. Because several of the tested polyphenols are known to be unstable in aqueous solution we conducted experiments with and without addition of Vitamin C or catalase. Addition of Vitamin C did not change the effect on SIRT1 activity significantly for resveratrol, quercetin, EC and ECg (Table 1). However, a striking finding was that EGCg, EGC, gallic acid and myricetin inhibited the activity of SIRT1 when the compounds were incubated without any stabilizing agents (Table 1). For example, the substrate deacetylation was approximately 25 times lower in the presence of EGCg than in the control reaction. Addition of 100 U/ml catalase negated the inhibitory effect of EGCg, whereas addition of 1 mM Vitamin C resulted in stimulation of SIRT1 (Fig. 3A). This indicates that the inhibition probably is an indirect effect caused by oxidation products of EGCg or by H2O2. To investigate whether formation of oxidation products of EGCg or H2O2 formation was responsible for the inhibition of SIRT1 activity, we preincubated EGCg for half an hour without Vitamin C, catalase, SIRT1 or substrate. SIRT1 and substrate were incubated afterwards with the preincubated solution with and without addition of stabilizing agents. Stabilizing agents again eliminated the inhibitory effects of polyphenols on SIRT1 activity (Fig. 3B). This suggests that H2O2 formation is the major process that caused the activity of the protein to decrease. H2O2 formation during EGCg incubations did not influence the developer reaction or AMC stability (data not shown). Myricetin, gallic acid and EGC also inhibited SIRT1 activity when no Vitamin C was added. With addition of Vitamin C, myricetin stimulated SIRT1 3.19 ± 0.6 fold (average ± S.D., Fig. 3C). All further incubations were done with the addition of 1 mM Vitamin C."


"Because most polyphenols are rapidly metabolized in epithelial cells before entering the blood, it is of relevance to test metabolites of these compounds to better simulate the effects of polyphenols in an in vivo system. In contrast to the stimulating effect of quercetin, one of the metabolites of quercetin (quercetin 3-O-â-glucuronide) did not show a stimulatory effect. In fact, a slight, but significant, inhibition of SIRT1 activity was seen for quercetin 3-O-â-glucuronide (Fig. 4). "

Mech Ageing Dev. 2006 Jul;127(7):618-27.

[dannov]

Why bold slight, and then not bold significant? You and I are only slightly (1/10 of a %) not identical, yet I'm sure we look nothing like each other.

[trh001]

Hey stillheader stop wasting your money on fish oil, and taken 3 softgels of Organic Flaxseed oil for only $6.59 for 200 softgels giving at least 1,200mg ALA plus 60mg of lignans. Just take daily with first meal:

http://www.swansonvi...CatalogId=10051

FLAXSEED OIL IS SUPERIOR TO FISH OIL, HERE'S WHY:

Increasing folate may increase blood levels of DHA an omega 3. Folate helps transport stored DHA from the liver into the bloodstream. [Mens Health Magazine, May 2006,p.40]

"A healthy man should get 1.6g of ALA per day."
[Prevention Magazine, May 2006, p.26]

But, supplementation with DHA directly (an omega-3 fatty acid found in fish oil) in healthy young men has been shown to decrease the activity of immune cells, such as natural killer (NK) cells, and to inhibit certain measures of inflammation in the test tube.17

17. Kelley DS, Taylor PC, Nelson GJ, et al. Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. [Lipids 1999;34:317–24]

But, supplementing with veggie Omega 3-ALA has shown to opposite immune system promoting not suppressing like DHA:

"Fight Disease with Flax. A 1-gram increase in daily intake of alpha-linolenic acid (ALA)can reduce a man's risk of developing pneumonia by 31%. ALA is an omega-3 fat that helps decrease infection risk by quelling inflammation and regulating blood sugar."[Mens Health Magazine, Feb 2006,p.40]

Flaxseed Oil Lowers Blood Pressure. The flaxseed
oil participants had on average a drop in their
systolic (top number) blood pressure from 120 to 110
mm Hg. Their diastolic (bottom number) blood pressures
dropped from 80 to 70 mm Hg.[Heart 2006; 92, 166–169]

Dietary supplementation with flaxseed oil lowers blood pressure.[Eur J Clin Nutr, 1/31/07]

"Fish haters can get strong bones too. Diets high in
alpha-linolenic acid may promote strong bones.[Nutrition Journal, January 16, 2007]

Fish Consumption Linked to Heart Abnormality.Fish oil & eating fish may actually boost the risk of atrial fibrillation in healthy people. It's possible that fish may promote the development of atrial fibrillation in healthy people but prevent it in people with heart conditions. American Heart Association only recommends fish or fish oil for those with heart disease.[Physicians' Health Study May 18, 2006]

"Alpha-linolenic acid (ALA) An Omega-3 fat found in a long term French Study to lower the risk of fatal heart attack by over one-third."[Prescription for Natural Healing Third Edition,(2000),p.418]

Men who gradually lose their hair at the front and/or crown of the head, beginning in their mid-twenties, are 50% more likely to develop prostate cancer.[Cancer Epidemiol Biomarkers Prev 2000;9:523-7]

"HAIR-TRIGGER DIABETES. Young men with thinning ahir are at greater risk of diabetes. Those who started balding before age 30 were more likely to be insulin resistant-raising their risk of diabetes- than men with hair to spare. If you see scalp in your 20s, get a fasting blood-glucose test. Levels over 100mg per deciliter signal trouble."[Mens Health Magazine, Mar 2007, p.38]

"FLAXEN HAIR. Men who were losing their hair on 50mg a day of lignans, phytonutrients found in flaxseed. Flax may halt the progress of a receding hairline. Flax lignans help balance the formation of male hormones  that are responsible for hair loss."{Mens Health Magazine. Sep 2005, p.54]

Ordinary Flaxseed oil softgels can be bad only because like white bread is to whole grain. The bran which contains the anti-cancer compound IP-6 is in the bran. Well, each 1,000mg flaxseed oil softgel should always be accompanied by 20mg of SDG lignans per softgel thats why many supplement companies now provide 20mg SDG lignans per flaxseed oil softgel like Jarrow Formulas Flax Max sotfgels:

http://www.jarrow.co....php?prodid=220

http://www.elib.gov....chunkiid=128580

[ Aizer acknowledged that the study didn't rely on "gold standard" methods, such as double-blind, placebo-controlled research. So, it's possible that another unknown factor could explain the rise in atrial fibrillation cases seen in study participants, he said. That possibility makes sense to Dr. Marie-Noelle Langan, chief of electrophysiology at Lenox Hill Hospital in New York City. She said it's possible that the male doctors who ate a lot of fish each week were health-minded athletes, who can be prone to atrial fibrillation. "It's possible this is a group of very fit people who run like maniacs," Langan said. "It doesn't take that many patients to throw off the statistics." Langan's hospital plans to launch its own study into fish oil and atrial fibrillation. ]


1: J Am Coll Cardiol. 2006 Aug 1;48(3):478-84. Epub 2006 Jul 12. Links
Dietary fish and n-3 fatty acid intake and cardiac electrocardiographic parameters in humans.Mozaffarian D, Prineas RJ, Stein PK, Siscovick DS.
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. dmozaffa@hsph.harvard.edu

OBJECTIVES: We evaluated the association between dietary fish intake and several cardiac electrocardiographic parameters in humans relevant to arrhythmic risk. BACKGROUND: Fish consumption may reduce the incidence of sudden death and atrial fibrillation, possibly related to anti-arrhythmic effects. METHODS: In a population-based study of 5,096 men and women, we evaluated cross-sectional associations between usual dietary fish intake and electrocardiographic measures of heart rate, atrioventricular conduction (PR interval), ventricular repolarization (QT interval), and ventricular conduction (QRS interval). Multivariate models were adjusted for age, gender, race, education, smoking, body mass index, diabetes, coronary heart disease, physical activity, and intakes of beef or pork, fried fish, fruits, vegetables, alcohol, and total calories. RESULTS: Consumption of tuna or other broiled or baked fish (comparing the highest to the lowest category of intake) was associated with lower heart rate (-3.2 beats/min, 95% confidence interval [CI] = 1.3 to 5.1; p trend <0.001), slower atrioventricular conduction (PR interval +7.2 ms, 95% CI = 1.4 to 12.9; p trend = 0.03), and substantially lower likelihood of prolonged QT (relative risk = 0.50, 95% CI = 0.27 to 0.95; p trend = 0.03). Tuna/other fish intake was not associated with ventricular conduction (p = 0.60). Findings were similar for estimated intake of marine n-3 fatty acids: a 1 g/day higher intake was associated with 2.3 beats/min lower heart rate (95% CI = 0.9 to 3.7), 7.6 ms longer PR interval (95% CI = 3.3 to 11.9), and 46% lower likelihood of prolonged QT (relative risk = 0.54, 95% CI = 0.33 to 0.88). CONCLUSIONS: These findings in this large, population-based study suggest that dietary fish intake is associated with cardiac electrophysiology in humans, including heart rate, atrioventricular conduction, and ventricular repolarization, with potential implications for arrhythmic risk.

PMID: 16875972 [PubMed - indexed for MEDLINE]


1: Am Heart J. 2006 Apr;151(4):857-62. Links
Intake of very long-chain n-3 fatty acids from fish and incidence of atrial fibrillation. The Rotterdam Study.Brouwer IA, Heeringa J, Geleijnse JM, Zock PL, Witteman JC.
Wageningen Centre for Food Sciences, Wageningen, The Netherlands. ingeborg.brouwer@wur.nl

BACKGROUND: Atrial fibrillation is the most common sustained cardiac arrhythmia. It is a major cause of morbidity and mortality through an increased risk of thromboembolic stroke. Experimental as well as observational evidence suggests that n-3 polyunsaturated fatty acids may have antiarrhythmic effects. The objective of this study was to examine whether high intakes of fish and its very long-chain n-3 fatty acids eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) are associated with risk of incident atrial fibrillation. METHODS: We used data from the Rotterdam Study, a prospective cohort study. At baseline, dietary intake data were available for 5184 subjects free from atrial fibrillation. Dietary intake was assessed using a semiquantitative food-frequency questionnaire, and incidence of atrial fibrillation was continuously monitored during follow-up. Cox proportional hazards model (adjusted for lifestyle and disease factors) was used to examine the associations between intakes of EPA plus DHA and of fish with atrial fibrillation. RESULTS: After a mean follow-up of 6.4 (+/-1.6) years, 312 subjects developed atrial fibrillation. Intake of EPA and DHA in the third textile compared with first was not associated with risk of atrial fibrillation (relative risk 1.18, 95% CI 0.88-1.57). Furthermore, no association was observed with intake of >20 g/d fish compared with no fish intake (relative risk 1.17, 95% CI 0.87-1.57). CONCLUSIONS: In this study, intakes of EPA and DHA and the consumption of fish were not associated with the onset of atrial fibrillation. This finding does not support that n-3 fatty acids have a general antiarrhythmic effect.

PMID: 16569549 [PubMed - indexed for MEDLINE]


n-3 Fatty acids consumed from fish and risk of atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study.Frost L, Vestergaard P.
Department of Cardiology and the Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Aarhus University Hospital, Aarhus, Denmark. rlg041fr@as.aaa.dk

BACKGROUND: Experimental studies have shown that n-3 polyunsaturated fatty acids in fish may have antiarrhythmic properties. OBJECTIVE: We examined the association between consumption of n-3 fatty acids from fish and risk of atrial fibrillation or flutter. DESIGN: In a prospective cohort study of 47 949 participants (mean age: 56 y) in the Danish Diet, Cancer, and Health Study, we investigated the relation between the consumption of n-3 fatty acids from fish estimated from a detailed semiquantitative food questionnaire and risk of atrial fibrillation or flutter. The subjects were followed up in the Danish National Registry of Patients for the occurrence of atrial fibrillation or flutter and in the Danish Civil Registration System (vital status and emigration). The consumption of n-3 fatty acids from fish was analyzed as sex-specific quintiles with the use of Cox proportional hazards models. RESULTS: During follow-up (x: 5.7 y), atrial fibrillation or flutter had developed in 556 subjects (374 men and 182 women). When the lowest quintile of n-3 fatty acids consumed from fish was used as a reference, the unadjusted hazard rate ratios in quintiles 2, 3, 4, and 5 were 0.93, 1.11, 1.10, and 1.44, respectively (P for trend = 0.001). The corresponding adjusted hazard rate ratios were 0.86, 1.08, 1.01, and 1.34 (P for trend = 0.006). Inclusion of information on the frequency of fatty fish consumption did not alter these associations. CONCLUSIONS: Consumption of n-3 fatty acids from fish was not associated with a reduction in risk of atrial fibrillation or flutter. We cannot exclude the possibility of residual confounding caused by a lack of information on intake of fish-oil tablets.

PMID: 15640459 [PubMed - indexed for MEDLINE]

[niner]

I am taking the AOR product. Trust me, (read my last few posts in the 500mg club thread,) the quercitin/luteolin/piperine mix definitely was inhibiting my P450 'zimes, just as intended. Hopefully it is increasing my free t-res levels as well.

I can happily report that today I took my Paxil 8 hours after my morning does of AOR acta-tres, and I had no problems.

Do you have information about the timecourse of cyp enzyme inhibition, eight hours does not seem that much?

For example, grapefuit juice can inhibit cyp 3A4 substantially up to three days (sic!). The effect is of course drug dependent (+I was under the impression grapefruit inhibits mostly intestinal cyp) but for example concominant ingestion of grapefruit and simvastatin increased simvastatin peak concentration (Cmax) and area under curve (AUC) 12 and 13.5 fold compared to no grapefruit juice (!!!!!!), respectively, whereas the numbers were 2.4 and 2.1 when ingesting simvastatin 24hrs after grapefruit juice and 1.5 and 1.4 when ingesting simvastatin 3 days after grapefruit juice.

http://www.powernetd.../mechanism.html

I would imagine the timecourse of the recovery would be more dependent on the inhibited enzymes themselves rather the substance inhibiting.

This response is to an old post, but I just saw it and can clear up a mystery here. Grapefruit juice is a rather unusual 3A4 inhibitor in that it is covalently bound to the enzyme. Once the grapefruit compound hits the 3A4, it is permanently inhibited until it is replaced by a new copy. That is why the timecourse of the inhibition is so long, because it is determined by the turnover time of the enzyme. Most P450 inhibitors are non-covalent. They inhibit only as long as there is a high enough concentration to ensure that the enzyme has an inhibitor (non-covalently) bound in it. When that concentration drops due to the compound washing out, the enzyme is no longer inhibited. So for the vast majority of p450 inhibitors, inhibition is dependent on the serum concentration of the inhibitor, which typically hangs around for hours rather than days.

[trh001]

Why bold slight, and then not bold significant?  You and I are only slightly (1/10 of a %) not identical, yet I'm sure we look nothing like each other.

How meaningful might the potential antagonism be? It's existence may be statistically significant in a given study, even reproducible across studies, such that one can generate good confidence intervals and make good predictions...but it's impact may be of no consequence given the small magnitude, or, more to the point, for a given consumer of the information who has an interest in magnitude above a certain level. Example: an alternative fuel source may reliably and statistically meaningfully reduce your cars engine life by 1 year for every 100 years of use. If it costs 50% less than existing products, the savings will offset the loss of engine life.

[dannov]

But the question is, until further research is done, do you really want to mess with something that can inhibit your SIRT1? Remember that it is not natural to consume 500mg-2g of Quercetin a day...it's found in trace amounts in apple skins and onions and what-not. What might work for the body when consumed naturally may not work when consumed from an extracted, concentrated pill. Too much of anything is usually bad.

More research before I can safely mess with Quercetin. Methylated Chrysin has potential atm from studies that I've seen.

[trh001]

But the question is, until further research is done, do you really want to mess with something that can inhibit your SIRT1?  Remember that it is not natural to consume 500mg-2g of Quercetin a day...it's found in trace amounts in apple skins and onions and what-not.  What might work for the body when consumed naturally may not work when consumed from an extracted, concentrated pill.  Too much of anything is usually bad. 

More research before I can safely mess with Quercetin.  Methylated Chrysin has potential atm from studies that I've seen.

No, I don't. No endorsement implied.

Still, if one is taking Quercetin (as folks on this list seem to be), it might be comforting to know that the effect of the active metabolite noted above is (perhaps) limited, and may not rival, say, the SIRT1 inhibition of nicotinamide of IC50<50uM (1)...that some ingest in the form of their daily (mega?) multivitamin. "Our findings also suggest that the medicinal use of nicotinamide should be given careful consideration." (1) AFAIK, this charming attribute does not extend to nicotinic acid (niacin), btw.

"We have shown that the potency of nicotinamide rivals that of the most effective synthetic Sir2 inhibitors identified thus far. The fact that SIRT1 is inhibited by such low concentrations of nicotinamide in vitro raises the possibility that this mode of inhibition may be physiologically relevant. Levels of nicotinamide in mammalian tissues have been reported to lie in the range of 11-400 µM (41, 58-60). More recently, levels of nicotinamide in cerebrospinal fluid were determined with high accuracy to be 54.2 µM (61), a value that is similar to the IC50 for nicotinamide reported here. We propose that fluctuations in cellular nicotinamide levels may directly control the activity of Sir2 proteins in vivo. These fluctuations may in turn be regulated by enzymes involved in nicotinamide metabolism, including Pnc1." (1)

"Nicotinamide and nicotinic acid are used at high doses (up to 10 g/day) to self-treat a wide variety of ailments (43). Both are considered forms of vitamin B3 and are often used interchangeably, although nicotinamide has become preferred in many cases because of an apparent lack of side effects. We have shown that these two related compounds have drastically different effects at the molecular level. In addition, nicotinamide is currently in trials as a therapy to prevent cancer recurrence and insulin-dependent (type I) diabetes (42). Our results clearly demonstrate that nicotinamide can inhibit Sir2 enzymes, even in noncycling cells, and raise the concern that there may be deleterious consequences of long term nicotinamide therapy in humans. " (1)

1) J. Biol. Chem., Vol. 277, Issue 47, 45099-45107, November 22, 2002, "Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1"

[neogenic]

But the question is, until further research is done, do you really want to mess with something that can inhibit your SIRT1?  Remember that it is not natural to consume 500mg-2g of Quercetin a day...it's found in trace amounts in apple skins and onions and what-not.  What might work for the body when consumed naturally may not work when consumed from an extracted, concentrated pill.  Too much of anything is usually bad. 

More research before I can safely mess with Quercetin.  Methylated Chrysin has potential atm from studies that I've seen.

Methylated chrysin? You have a link for that study? Is this form, by methylation, improve bioavailability. As I remember, chrysin has much potential but that was the catch, very poor oral bioavailability.

How about DHQ (di-hydro-quercetin) over megadosing plain quercetin?

[dannov]

Ya, I can pull up a few studies for you hopefully later today. Chrysin's problem is that it has poor gut/intestinal absorption, whereas Res makes it fine past that, but not so much in the liver (gluc/sulf enzymes). If Chrysin were to make it to the liver, it could potentially preferentially be sulfated and glucorinated, meaning more Res uptake into bloodstream. What I've found with Methylated Chrysin, however, is that it makes it very well into the bloodstream meaning that it bypasses both gut/intestinal and liver hindrances, which means it probably wouldn't influence resveratrol much (though you would be getting the benefits of Chrysin, and otherwise relatively worthless supplement due to absorption issues).

The study that I saw that used the Methylated Chrysin obtained it from IndoFine (if memory serves me right). Well, I tracked down that site and e-mailed them to see if I could get my hands on some Methylated Chrysin, but they replied with "sorry, we do not sell our chemicals as supplements nor for personal research" (I referred to it as personal research figuring I might be able to lend some fake legitimacy as a study to it, heh).

There is otherwise no way that I have seen to obtain Methylated Chrysin, and the studies are quite new (this summer I believe). I did also exchange a couple e-mails with the scientist associated with the studies.

I can't comment on di-hydro-quercetin without properly researching it. Sorry. :(

[hormesis]

Though resveratrol serum levels may be higher with quercetin in the mix, it ma no longer activate SIRT1 due to inhibitin by this metabolite. I believe this is the case, having tried adding quercetin to my regimen: the COX2 effects (reduction of inflamation) were greater, but the deep long term pain from arthritis becam worse within three days (SIRT1 mediates inhibition of NF Kappa, which improves arthritis symptoms.)

How much quercetin were you taking?

Bump on this question to maxwatt.

I'm on the verge of dropping quercetin and would like to know what dose Max tried out.

[maxwatt]

Though resveratrol serum levels may be higher with quercetin in the mix, it ma no longer activate SIRT1 due to inhibitin by this metabolite. I believe this is the case, having tried adding quercetin to my regimen: the COX2 effects (reduction of inflamation) were greater, but the deep long term pain from arthritis becam worse within three days (SIRT1 mediates inhibition of NF Kappa, which improves arthritis symptoms.)

How much quercetin were you taking?

Bump on this question to maxwatt.

I'm on the verge of dropping quercetin and would like to know what dose Max tried out.

500 mg. There was some bromelain in it too. The reason people think it helps is that it is preferentially sulfonated, sparing resveratrol so that in theory more of it gets to the cells. I found it weakened the effect of the resveratrol I was taking, in that the anti-arthritic effect I obtained from resveratrol disappeared when I added 500 mg of quercetin to my regimen. (I was taking about 1.5 gram of resveratrol at the time.)

I found a paper which I cited earlier in this thread (or perhaps another) which showed grapefruit (or its component naringin) is as good as quercetin for purposes of blocking sulfonation. I've been drinking about 4 oz of grapefruit juice with my evening resveratrol, sometimes with a little vodka in it, and estimate it increases the effective dose of resveratrol by a factor of 1.5 to 2; this is an estimate based on the degree of pain relief and absence of inflammation I feel from osteoarthritis, especially in my right big toe.

FWIW, piperine or black pepper is preferentially glucoronidated, so in theory more resveratrol gets through the intestines and by the liver, though I've concluded that sulfonation is a greater problem. Rather than add biopterin, I take my resveratrol with or shortly after my evening meal, which is usually seasoned with some pepper.

craig5277 suggested cranberry juice increased the efficacy of resveratrol; others have not noticed an effect. It is possible the berry contains some flavanoid or phytochemical that also is sulfonated or glurcoronated, sparing resveratrol and increasing its efficacy. Perhaps. The substances in cranberries are not well enough studied or characterized, and there are several species sold as cranberry, likely with different chemical profiles.

My conclusions are based admittedly on subjective experience, supported by some papers, and some inferences. YMMV. I would be pleased if others reported whether grapefruit juice seemed to increase the effects of resveratrol, or not. My own experience is that resveratrol's effects were undeniable only in doses greater than 500 mg, and increased with the dose, up to 5 grams, which is the most I've tried. At that level, I noted irritable bowel syndrome unless I cut back. Others have such symptoms at lower doses, some tolerate higher. I'm currently oscillating between 4 and 3.5 grams. I've considered dosing every 36 hours, but haven't tried it yet. I use a 98% plant extract, the current batch has tested as 98.6% trans-resveratrol, with no measurable heavy metals.

[niner]

I've considered dosing every 36 hours, but haven't tried it yet.

I've recently switched from once a day dosing to a double dose every two days. This is strictly based on theoretical concerns that high plasma levels are critical to induce the desired gene-switching events, and my suspicion that those events have a fairly long half life. One might consider it the analog of alternate day fasting, which has some precedence in the literature as a Good Thing.

I was previously taking about a gram a day, now two grams every other day. I have no idea whether either protocol is doing anything useful. I have some blood work coming up in a couple months- maybe that will show something.