20 replies to this topic

[chennai01]

My integrative physician has put me on a megadose of quercetin for the last 8 months to reduce inflammation with my psoriatic/rheumatoid arthritis. This dose is far higher than I imagine anyone takes.

The dose is 16,500 mg/day split up into 3 doses on an empty stomach and has been somewhat helpful.

Is this safe?

[dannov]

Holy SIRT1 inhibition Batman!

I'll link you to something that I just shared with Maxwatt:

http://www.nutrasanus.com/ginger.html

That helps a good deal with rheumatoid arthritis.

[chennai01]

Holy SIRT1 inhibition Batman!

I'll link you to something that I just shared with Maxwatt:

http://www.nutrasanus.com/ginger.html

That helps a good deal with rheumatoid arthritis.

Already taking about 2.4 grams of ginger (60 MG standarized) among a multitude of things for arthritis, fibromyalgia and severe fatigue issues.

[health_nutty]

That's a lot of quercitin!

[dannov]

That site I linked ya recommends 2-4; might want to try taking more. Also, Resveratrol--2g of pure Trans-Res a day to 3g has done wonders for Maxwatt's osteoarthritis.

[chennai01]

That site I linked ya recommends 2-4; might want to try taking more.  Also, Resveratrol--2g of pure Trans-Res a day to 3g has done wonders for Maxwatt's osteoarthritis.

Have tried reservatrol in the past - didn't notice much difference. Am taking 300 mgs of grape seed extract (with the quercetin) a day in 3 seperate doses.

[Matt]

Tried Green tea extract? I would assume you're taking high dose omega 3 too?

How has your C reactive protein and other inflammation markers changed since taking supplements? Has there been a big effect?

[chennai01]

Tried Green tea extract? I would assume you're taking high dose omega 3 too?

How has your C reactive protein and other inflammation markers changed since taking supplements? Has there been a big effect?

Yes, you nailed that one. Green tea is one of the few substances I found that makes an immediate and noticeable difference (more flexible, less pain ,etc.) On weekends I drink 14 cups and on weekdays I drink 8-10 cups and take Life Extension's Green tea pill (can't be running to the bathroom constantly at work!). I find the real green tea is much better than the equivalent pill dose.

Also, take large doses of fish oil and borage oil. Fish oil: EPA = 2520 MG, DHA = 1680 MG per day. GLA (with Sesame Ligans) = 1680 MG/Day

My C Reactive Protein and Homocysteine levels have remained high despite the supplements and an extremely strict anti-inflammatory diet. However, I had already started the diet and many of the supplements before these tests. My level of inflammation used to be much higher (was on enbrel and popped NSAIDs regularly) and my psoriasis is vastly improved.

[Matt]

If I remember correctly Green tea seems to inhibit Nf-kappB thus decreases TNF-a. I think TNF-a is now a target for people with R.A which has helped my uncle a lot!

I noticed that when I had something called 'reactive arthritis' due to food poisoning, green tea was the ONE THING that really made a difference and prevented any sort of swelling on the joints affected.

Fasting or a mild cr would also be something well worth looking into. In fact, it may very well be that either one of these could prolong the lives of people who have autoimmune disorders such as R.A which used to (dont know with the new drugs) accelerate aging quite dramatically.

Edited by Matt, 24 September 2007 - 10:59 PM.

[chennai01]

If I remember correctly Green tea seems to inhibit Nf-kappB thus decreases TNF-a.  I think TNF-a is now a target for people with R.A which has helped my uncle a lot!

I noticed that when I had something called 'reactive arthritis' due to food poisoning, green tea was the ONE THING that really made a difference and prevented any sort of swelling on the joints affected.

Fasting or a mild cr would also be something well worth looking into. In fact, it may very well be that either one of these could prolong the lives of people who have autoimmune disorders such as R.A which used to (dont know with the new drugs) accelerate aging quite dramatically.

Yes, TNF-alpha is the cytokine that most of the new biologic drugs target (such as enbrel, which I used to take). Unfortunately, the immune-system suppression is too extreme (potential for increased risk of cancer, chronic infections, inability to heal wounds, etc.). My strategy has been to suppress various inflammatory cytokines, such as TNF-alpha. Quercetin was one substance that appears to do that, but when I went to my doctor he increased my fairly normal dose drastically.

What is a cr?

[resveratrol]

What is a cr?

Caloric restriction.

[dannov]

That site I linked ya recommends 2-4; might want to try taking more.  Also, Resveratrol--2g of pure Trans-Res a day to 3g has done wonders for Maxwatt's osteoarthritis.

Have tried reservatrol in the past - didn't notice much difference. Am taking 300 mgs of grape seed extract (with the quercetin) a day in 3 seperate doses.

How much res per day? If you were using a pill form, chances are it was too low to make a real difference.

[chennai01]

That site I linked ya recommends 2-4; might want to try taking more.  Also, Resveratrol--2g of pure Trans-Res a day to 3g has done wonders for Maxwatt's osteoarthritis.

Have tried reservatrol in the past - didn't notice much difference. Am taking 300 mgs of grape seed extract (with the quercetin) a day in 3 seperate doses.

How much res per day? If you were using a pill form, chances are it was too low to make a real difference.

Not sure, but it was the highest dose Swanson offered. Its something I'd consider, but my supplement list is ridiculously large and I'm trying to keep my budget within reasonable limits.

[dannov]

Ya, if you got it pilled, then it's essentially worthless. Their "super" potency is only 100mg...that won't do jack.

http://www.swansonvi...Id=16823&R=5072

Maxwatt reported using around 1.5g-3g before reversing his osteoarthritis. You do this by buying a kilo of the powder, measuring out your own amounts with a cheap scale (I got a pocket digital scale for <$30 off the web) in about 2g of Miralax (10 bucks at a store), mixed all together, and drink it down. Taking 2 Bioperine caps with it may also help with absorption.

Biotivia, Revgenetics, Megaresveratrol are also cappers that I'd trust for good value for your money. None of the major supp. companies know jack about res though, they just jumped on the bandwagon knowing that unsuspecting customers would buy the product and thus throwing their money away (Res has low bioavailability issues so you need larger amounts).

If it means scrapping a few other worthless supps to get something that may very well cure your problem, then it's definitely worth it.

[krillin]

Maxwatt also said that he got noticeable resveratrol-like effects from milk thistle. His approximate conversion factor was 175 mg of 80% extract = 50 mg resveratrol. That would be a cheaper alternative.

[krillin]

One possible concern is depletion of phase II conjugates like methyl groups. With your high homocysteine, I'd take several grams of TMG.

This thesis says on page 26 that in humans, the quercetin metabolite pattern is 35% sulfated, 46% glucuronidated, and 19% methylated and glucuronidated.

Toxicol Appl Pharmacol. 1994 Mar;125(1):149-58.
Quercetin increases the severity of estradiol-induced tumorigenesis in hamster kidney.
Zhu BT, Liehr JG.
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031.

Catechol estrogens have been postulated to mediate estradiol-induced kidney tumorigenesis in Syrian hamsters. As part of an examination of this postulate, we studied the influence of quercetin, a polyphenolic flavonoid, on the incidence and severity of estrogen-induced kidney tumors, on the metabolic activation of estradiol to catechol estrogens, and on the inactivation of catechol estrogens by catechol-O-methyltransferase-mediated O-methylation. None of the hamsters treated with 0.3 or 3% quercetin in the diet for 5.7 or 6.5 months, respectively, developed tumors, whereas all animals treated with estradiol developed kidney tumors. The coadministration of estradiol plus 3% quercetin significantly (p < 0.05) increased the mean number of large tumor nodules and the incidence of abdominal metastases over values obtained with hormone treatment alone. The coadministration of estradiol plus 0.3 or 3% quercetin for 16 days increased renal NADPH-dependent estradiol-4- but not estradiol-2-hydroxylase activities by 91 or 73%, respectively, over values obtained with hormone treatment alone. In vitro, quercetin and its structural analog, fisetin, strongly inhibited the catechol-O-methyltransferase-catalyzed O-methylation of 60 microM 4-hydroxyestradiol, with IC50 values of approximately 2-4 microM. Kinetic analyses of the enzyme inhibition by quercetin and fisetin revealed a mixed-type of inhibition (competitive plus non-competitive). Combined treatment of estradiol plus 3% quercetin decreased the rates of kidney catechol-O-methyltransferase-catalyzed O-methylation of 2- and 4-hydroxyestradiol by 34 and 22%, respectively, from values obtained with hormone treatment alone. Rates of hamster liver and kidney microsome-mediated estrogen quinone formation and quinone reduction (redox cycling) in estradiol plus 3% quercetin-treated hamsters were not markedly altered compared to values obtained in estradiol-treated animals. It is concluded that increased rates of formation of 4-hydroxyestradiol combined with an inhibition of the inactivation of this catechol estrogen by catechol-O-methyltransferase may result in elevated levels of this estrogen metabolite, specifically in the hamster kidney, where it may undergo metabolic redox cycling and generate potentially mutagenic free radicals. Thus, the potentiation by quercetin of estradiol-induced tumorigenesis in hamster kidney supports a role of 4-hydroxyestradiol in estrogen-induced carcinogenesis in this species.

PMID: 8128490

[chennai01]

What is TMG?

These studies (from a quick skim through) do not cast a positive light on this substance.

This is the site for my physican's claim for the benefits of (his brand, which I do not buy anymore) quercetin:

http://alternative-m...s/quercitin.htm

Its obviously a hyped up sales pitch, but it does provide a reference. I'm sure if we dug up that reference, it would not be as enthusiastic as the marketing hype.

[chennai01]

The study below served as a basis for my supplementation of quercetin (at a more normal doseage):

Clin Vaccine Immunol. 2006 March; 13(3): 319–328.
doi: 10.1128/CVI.13.3.319-328.2006.
Copyright © 2006, American Society for Microbiology
The Flavonoid Quercetin Inhibits Proinflammatory Cytokine (Tumor Necrosis Factor Alpha) Gene Expression in Normal Peripheral Blood Mononuclear Cells via Modulation of the NF-êâ System
Madhavan P. Nair,* Supriya Mahajan, Jessica L. Reynolds, Ravikumar Aalinkeel, Harikrishnan Nair, Stanley A. Schwartz, and Chithan Kandaswami

Abstract

The flavonoids comprise a large class of low-molecular-weight plant metabolites ubiquitously distributed in food plants. These dietary antioxidants exert significant antitumor, antiallergic, and anti-inflammatory effects. The molecular mechanisms of their biological effects remain to be clearly understood. We investigated the anti-inflammatory potentials of a safe, common dietary flavonoid component, quercetin, for its ability to modulate the production and gene expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-á) by human peripheral blood mononuclear cells (PBMC). Our results showed that quercetin significantly inhibited TNF-á production and gene expression in a dose-dependent manner. Our results provide direct evidence of the anti-inflammatory effects of quercetin by PBMC, which are mediated by the inhibition of the proinflammatory cytokine TNF-á via modulation of NF-êâ1 and Iêâ.


http://www.pubmedcen...i?artid=1391952

[krillin]

What is TMG?

TMG is trimethylglycine. The capsules and tablets don't give effective doses, so powder is the best bet. I used Beyond a Century's before I learned that my homocysteine was only 3.0 micromolar. The lab actually flagged it as being too low.

[chennai01]

Interesting study on oral and intravenous quercetin on live rats.

Apparently, the had significant effects at 800 MG/KG and negligible effects at 150 mg/KG. My megadose is about 220 MG/KG per day.

Therapeutic and preventive properties of quercetin in experimental arthritis correlate with decreased macrophage inflammatory mediators

Pentahydroxyflavone dihydrate, quercetin (QU) is one of common flavonols biosynthesized by plants and has been suggested to modulate inflammatory responses in various models. In the present study, we investigated in vivo effects of oral or intra-cutaneous QU in chronic rat adjuvant-induced arthritis (AA). Growth delay and arthritic scores were evaluated daily after AA induction in Lewis rats. Oral administration of QU (5x 160mg/kg) to arthritic rats resulted in a clear decrease of clinical signs compared to untreated controls. Intra-cutaneous injections of lower doses (5 × 60 mg/kg) ofQU gave similar anti-arthritic effects, while 5x 30 mg/kg concentrations were inefficient in this respect. Finally, injection of relatively low QU doses (5 x 30 mg/kg) prior to AA induction significantly reduced arthritis signs. As QU was suggested to inhibit macrophage-derived cytokines and nitric oxide (NO), we then analyzed macrophage response ex uiuo. Anti-arthritic effects of QU correlated with significant decrease of inflammatory mediators produced by peritoneal macrophages, ex uiuo and in uitro. These data indicate that QU is a potential anti-inflammatory therapeutic and preventive agent targeting the inflammatory response of macrophages.
Revue / Journal Title
Biochemical pharmacology (Biochem. pharmacol.) ISSN 0006-2952 CODEN BCPCA6
Source / Source
2006, vol. 72, no10, pp. 1304-1310

[krillin]

Niner posted this back in April in the 500 club thread, but it definitely belongs here too.

J Nutr. 2005 Mar;135(3):525-31.
Low concentrations of flavonoids are protective in rat H4IIE cells whereas high concentrations cause DNA damage and apoptosis.
Wätjen W, Michels G, Steffan B, Niering P, Chovolou Y, Kampkötter A, Tran-Thi QH, Proksch P, Kahl R.
Institute of Toxicology, Heinrich-Heine-University, 40001 Düsseldorf, Germany. wim.waetjen@uni-duesseldorf.de

Dietary flavonoids possess a wide spectrum of biochemical and pharmacological actions and are assumed to protect human health. These actions, however, can be antagonistic, and some health claims are mutually exclusive. The antiapoptotic actions of flavonoids may protect against neurodegenerative diseases, whereas their proapoptotic actions could be used for cancer chemotherapy. This study was undertaken to determine whether a cytoprotective dose range of flavonoids could be differentiated from a cytotoxic dose range. Seven structurally related flavonoids were tested for their ability to protect H4IIE rat hepatoma cells against H(2)O(2)-induced damage on the one hand and to induce cellular damage on their own on the other hand. All flavonoids proved to be good antioxidants in a cell-free assay. However, their pharmacologic activity did not correlate with in vitro antioxidant potential but rather with cellular uptake. For quercetin and fisetin, which were readily taken up into the cells, protective effects against H(2)O(2)-induced cytotoxicity, DNA strand breaks, and apoptosis were detected at concentrations as low as 10-25 micromol/L. On the other hand, these flavonoids induced cytotoxicity, DNA strand breaks, oligonucleosomal DNA fragmentation, and caspase activation at concentrations between 50 and 250 micromol/L. Published data on quercetin pharmacokinetics in humans suggest that a dietary supplement of 1-2 g of quercetin may result in plasma concentrations between 10 and 50 micromol/L. Our data suggest that cytoprotective concentrations of some flavonoids are lower by a factor of 5-10 than their DNA-damaging and proapoptotic concentrations.

PMID: 15735088