There are other natural anti-inflammatories such as omega-3 and alpha-lipoic acid, but I'm already taking these (upped my dose of the former last night and - coincidence or not - slept like a log!).
So I have been looking into resveratrol and curcumin. I don't have time to edit my notes so will just paste them here. NB the links to places to buy them are for the UK - cos that's where I am and I made the notes for me!
NOTES ON RESVERATROL AND CURCUMIN
Innate Immun. 2013 Oct 22. [Epub ahead of print]
cis-Resveratrol produces anti-inflammatory effects by inhibiting canonical and non-canonical inflammasomes in macrophages.
Huang TT1, Lai HC, Chen YB, Chen LG, Wu YH, Ko YF, Lu CC, Chang CJ, Wu CY, Martel J, Ojcius DM, Chong KY, Young JD.
Resveratrol, a natural phenolic compound found in red grapes and wine, exists as cis and trans isomers. Recent studies have shown that trans-resveratrol possesses anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-tumor and immunomodulatory properties. However, it remains unclear whether cis-resveratrol may exhibit similar activities. The objective of the present study was to examine the effects of cis- and trans-resveratrol on the production of pro-inflammatory cytokines and mediators in human macrophages. We examined the possibility that cis- and trans-resveratrol may affect cytokine secretion by modulating inflammasomes, intracellular multi-protein complexes, the assembly of which leads to caspase-1 activation and secretion of active IL-1β by macrophages. Our results show that pre-treatment of macrophages with cis-resveratrol not only reduces pro-IL-1β production and IL-1β secretion, but also suppresses ATP-induced transcription and activation of caspase-1 and caspase-4. Notably, cis-resveratrol inhibits the expression of the purinergic receptor, P2X7R, and the endoplasmic reticulum stress marker, Glc-regulated protein 78, but also reduces reactive oxygen species production. Moreover, cis-resveratrol attenuates cyclooxygenase-2 expression and prostaglandin E2 production. cis-Resveratrol also decreases the phosphorylation of p38 MAPK and expression of the c-Jun protein. These results indicate that cis-resveratrol produces anti-inflammatory effects by inhibiting both the canonical and non-canonical inflammasomes, and associated pathways in human macrophages.
Goes Well With
Other Bioflavonoids like Genistein or Quercetin, perhaps through them being AMPK activators
Quercetin, again, via competing for sulphation in the duodenum and liver (increases Resveratrol bioavailability)
Calcium-D-Glucarate and increasing anti-oxidative potential and anti-thrombic effects of Resveratrol
Indole-3-Carbinol and some models of cancer
Curcumin and some models of cancer
Melatonin and neuroprotection (brain health) and possibly cardioprotection
The lower end of supplementation tends to be for cardiovascular health, insulin sensitivity, and longevity for somebody who is otherwise unhealthy is 5-10mg daily. For persons who are otherwise healthy, dosages between the range of 150-445mg have been used (with no clear indication for what is the optimal dose).
Supplementing for cerebral blood flow requires a dose in the 250-500mg range whereas supplementation for aromatase inhibition requires 500mg as well.
Supplementation of resveratrol refers to trans-resveratrol exclusively.
A significant decrease in circulating TNFα levels have been detected with resveratrol supplementation; linked to antiinflammatory effects of resveratrol. (study on obese subjects)
Trans-resveratrol is commonly seen as the active form of resveratrol. As the simple change results in a largely different molecule, many actions seen from trans-resveratrol are not seen with cis-resveratrol. These actions include modulation of the inflammation response...
NF-kB is a regulatory gene that is stimulated by stress and inflammation, and induces cell proliferation and survival...
Trans- but not cis-resveratrol impairs angiotensin-II-mediated vascular inflammation through inhibition of NF-κB activation and peroxisome proliferator-activated receptor-gamma upregulation.
Rius C1, Abu-Taha M, Hermenegildo C, Piqueras L, Cerda-Nicolas JM, Issekutz AC, Estañ L, Cortijo J, Morcillo EJ, Orallo F, Sanz MJ.
Angiotensin II (Ang-II) displays inflammatory activity and is implicated in several cardiovascular disorders. This study evaluates the effect of cis- and trans (t)-resveratrol (RESV) in two in vivo models of vascular inflammation and identifies the cardioprotective mechanisms that underlie them. In vivo, Ang-II-induced arteriolar leukocyte adhesion was inhibited by 71% by t-RESV (2.1 mg/kg, i.v.), but was not affected by cis-RESV. Because estrogens influence the rennin-angiotensin system, chronic treatment with t-RESV (15 mg/kg/day, orally) inhibited ovariectomy-induced arteriolar leukocyte adhesion by 81%, partly through a reduction of cell adhesion molecule (CAM) expression and circulating levels of cytokine-induced neutrophil chemoattractant, MCP-1, and MIP-1alpha. In an in vitro flow chamber system, t-RESV (1-10 microM) undermined the adhesion of human leukocytes under physiological flow to Ang-II-activated human endothelial cells. These effects were accompanied by reductions in monocyte and endothelial CAM expression, chemokine release, phosphorylation of p38 MAPK, and phosphorylation of the p65 subunit of NF-kappaB. Interestingly, t-RESV increased the expression of peroxisome proliferator-activated receptor-gamma in human endothelial and mononuclear cells. These results demonstrate for the first time that the in vivo anti-inflammatory activity of RESV is produced by its t-RESV, which possibly interferes with signaling pathways that cause the upregulation of CAMs and chemokine release. Upregulation of proliferator-activated receptor-gamma also appears to be involved in the cardioprotective effects of t-RESV. In this way, chronic administration of t-RESV may reduce the systemic inflammatory response associated with the activation of the rennin-angiotensin system, thereby decreasing the risk of further cardiovascular disease.
(So could it replace perindopril?)
UMM suggest 50 - 200 mg daily for carpal tunnel syndrome here:
This looks good value:
Now Foods 200mg Natural Resveratrol Capsules - Pack of 60 Capsules £12.79 free postage on Amazon
Treatment with curcumin and resveratrol suppressed NF-κB-regulated gene products involved in inflammation (cyclooxygenase-2, matrix metalloproteinase (MMP)-3, MMP-9, vascular endothelial growth factor), inhibited apoptosis (Bcl-2, Bcl-xL, and TNF-α receptor-associated factor 1) and prevented activation of caspase-3. IL-1β-induced NF-κB activation was suppressed directly by cocktails of curcumin and resveratrol through inhibition of Iκκ and proteasome activation, inhibition of IκBα phosphorylation and degradation, and inhibition of nuclear translocation of NF-κB. The modulatory effects of curcumin and resveratrol on IL-1β-induced expression of cartilage specific matrix and proinflammatory enzymes were mediated in part by the cartilage-specific transcription factor Sox-9.
from http://mct.aacrjournals.org/content/8/8/2348.abstract (full text also available):
Curcumin blocks prostaglandin E2 biosynthesis through direct inhibition of the microsomal prostaglandin E2 synthase-1
Hinnak Northoff2 and
+ Author Affiliations
1Department of Pharmaceutical Analytics, Pharmaceutical Institute, University of Tuebingen, and 2Institute for Clinical and Experimental Transfusion Medicine, University Medical Center Tuebingen, Tuebingen, Germany
Prostaglandin E2 (PGE2) plays a crucial role in the apparent link between tumor growth and chronic inflammation. Cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1, which are overexpressed in many cancers, are functionally coupled and thus produce massive PGE2 in various tumors. Curcumin, a polyphenolic β-diketone from tumeric with anti-carcinogenic and anti-inflammatory activities, was shown to suppress PGE2 formation and to block the expression of COX-2 and of microsomal PGE2 synthase-1. Here, we identified microsomal PGE2 synthase-1 as a molecular target of curcumin and we show that inhibition of microsomal PGE2 synthase-1 activity is the predominant mechanism of curcumin to suppress PGE2 biosynthesis. Curcumin reversibly inhibited the conversion of PGH2 to PGE2 by microsomal PGE2 synthase-1 in microsomes of interleukin-1β–stimulated A549 lung carcinoma cells with an IC50 of 0.2 to 0.3 μmol/L. Closely related polyphenols (e.g., resveratrol, coniferyl alcohol, eugenol, rosmarinic acid) failed in this respect, and isolated ovine COX-1 and human recombinant COX-2 were not inhibited by curcumin up to 30 μmol/L. In lipopolysaccharide-stimulated human whole blood, curcumin inhibited COX-2–derived PGE2 formation from endogenous or from exogenous arachidonic acid, whereas the concomitant formation of COX-2–mediated 6-keto PGF1α and COX-1–derived 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid was suppressed only at significant higher concentrations. Based on the key function of PGE2 in inflammation and carcinogenesis, inhibition of microsomal PGE2 synthase-1 by curcumin provides a molecular basis for its anticarcinogenic and anti-inflammatory activities. [Mol Cancer Ther 2009;8(8):2348–55]
Curcumin is the active ingredient of turmeric, and is also found in limited amounts in Ginger. It is a potent anti-inflammatory and cancer preventative molecule, and similar to Fish Oil it seems to be an effective metabolic syndrome band-aid. Black Pepper greatly enhances absorption.
It exerts potent anti-inflammatory effects, and these anti-inflammatory effects seem to be quite protective against some form of cancer progression.
It has a poor oral bioavailability (a low percentage of what you consume is absorbed) and thus should be enhanced with other agents such as black pepper extract, called piperine. This is unless you want the curcumin in your colon (as it is a colon anti-inflammatory and can help with digestion), in which case you wouldn't pair it with an enhancement.
Doses up to 8g curcuminoids in humans have been shown to not be associated with much adverse effects at all...
There appears to be a decrease in disease states or conditions characterized by inflammation associated with curcumin ingestion, does not appear to be too discriminatory in which inflammatory states it benefits.
One of curcumin's most well-researched effects on inflammation is inhibiting TNF-a induced activation and nuclear translocation of NF-kB, a protein that influences the genetic code to produce inflammatory cytokines. This has been seen in immune cells after oral ingestion of 150mg curcumin (Resveratrol at 75mg, Green Tea Catechins at 150mg, and soy at 125mg as confounders) but also in isolation in vitro and in vivo. Activation of NF-kB can increase protein content (amounts) of Cyclooxygenase-2 (COX-2), a pro-inflammatory enzyme; pretreatment with curcumin reduces COX-2 upregulation induced by inflammatory cytokines. Other pro-inflammatory enzymes that are suppressed by curcumin are iNOS, LOX (directly inhibited), and Phospholipase A2 (directly.)
Curcumin can reduce inflammation through a variety of means; preventing pro-inflammatory signals from acting on the nucleus (NF-kB related), reducing the ability of immune cells to get to sites of inflammation (adhesion related), and reducing the exacerbation of already present inflammation by reducing the activity of inflammatory enzymes (COX2, LOX related).
Other notable products downstream of NF-kB that are reduced by curcumin administration are cyclooxygenase-2 (COX-2), cyclin D1, adhesion molecules, MMPs, inducible nitric oxide synthase, Bcl-2, Bcl-xL, and tumor necrosis factor (TNF)...Curcumin appears to directly inhibit IKKβ as the method of reducing NF-kB translocation.
Curcumin tends to be most relevant to the colon due to its poor oral bioavailability. Oral bioavailability is a measure of how much of a molecule as a percentage is absorbed from the gut, and whatever is left over (in this case, a large amount) is carried on to the colon where it may interact with colonic microflora or the colonic walls.
Demonstrated to have protective effects on the kidneys in clinical settings...
Dosages of 6g daily have been associated with minor flatulence and a yellowing of the stool, both of which stopped after supplement cessation.
UMM say “Turmeric (Curcuma longa) standardized extract, 300 mg 3 times a day, for pain and inflammation.” for carpal tunnel syndrome here:
http://www.gvtc.co.uk/veganicity/turmericextra.html contains curcumin, bromelain, black pepper and ginger. £11.95 / 30 caps
Now Foods Curcumin Turmeric (665mg of Total Curcuminoids, 60 Vegetarian Capsules) is £12.41 + FREE UK delivery on Amazon.
NB some companies use a branded form of piperine called BioPerine.
Source Naturals Turmeric Extract - 95% Curcumin, 50 Tabs contains this, plus bromelain, and is stated to be vegetarian. 50 tabs £8.46 + FREE UK delivery on Amazon. 333mg curcuminoids per tab, 1-3 tabs. This is the page:
EDIT 20TH JUNE - 333 MG CURCUMINOIDS, NOT 33 MG! (Now corrected)