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jimmylegs
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2017 review: Essential Medicinal Chemistry of Curcumin

Post by jimmylegs » Sun Oct 07, 2018 9:18 am

The Essential Medicinal Chemistry of Curcumin
fft: https://pubs.acs.org/doi/10.1021/acs.jmedchem.6b00975

Abstract
Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.
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2017 correspondence: Don't discount all curcumin trial data

Post by jimmylegs » Sun Oct 07, 2018 9:39 am

Don't discount all curcumin trial data (2017)
https://www.nature.com/articles/543040c

We (royal we it's one guy) argue that the clinical potential of the spice extract curcumin should not be dismissed simply on the grounds that it yields confusing results in molecular drug screens (Nature 541, 144–145; 2017; see also K. M. Nelson et al. J. Med. Chem. http://doi.org/bw46; 2017).

Nelson and colleagues claim a lack of evidence for curcumin's therapeutic benefits “despite thousands of research papers and more than 120 clinical trials” (www.clinicaltrials.gov). However, a PubMed search under 'curcumin double-blind placebo-controlled clinical trial' yields 49 entries, of which 17 recent trials show efficacy. In addition, there are 27 other clinical trials and at least 5 animal studies of curcumin that point to therapeutic benefits (see full reference list in Supplementary information).

The assumption that a drug candidate must have a single known target and compatibility with high-throughput screening to enter the clinic can preclude promising drug candidates (R. L. Elliott Am. Chem. Soc. Med. Chem. Lett. 3, 688–690; 2012). Current detection methods for target engagement cannot gauge the full pharmacological spectrum of an investigational drug, so should be used with other screening paradigms. Also, the binding behaviour of curcumin to multiple molecular targets is associated with modulation rather than outright inhibition. And high-throughput screening is prone to technical artefacts that can make it a deceptive arbiter for excluding potential drugs.

In light of these considerations, curcumin's molecular targets and their regulatory mechanisms warrant further investigation if we are to build on the promising results that are already to hand in humans and animals.
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don't let suboptimal self care muddy any underlying diagnostic picture!

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Re: 2017 correspondence: Don't discount all curcumin trial d

Post by ElliotB » Sun Oct 07, 2018 11:27 am

I have been taking Curcumin for several years and like every other supplement I take, I have no idea whether it is helping or not. I can only hope that it and the others I take are indeed having a positive effect, who knows...

I think unlike many drugs where the desired outcome often occurs quickly and is obvious (if it is working), natural supplements often take much much longer to work (if they work at all). I don't think typically there is any way of knowing, and a leap of faith is required (crossing your fingers may also be beneficial).

The dietary supplement industry is largely unregulated, so the companies offering supplements can make unsubstantiated claims and you really never know for sure if you are getting the product purchased as detailed on the package - such a deal!

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Re: 2017 correspondence: Don't discount all curcumin trial d

Post by NHE » Sun Oct 07, 2018 10:21 pm

ElliotB wrote:I have been taking Curcumin for several years and like every other supplement I take, I have no idea whether it is helping or not. I can only hope that it and the others I take are indeed having a positive effect, who knows...
A regular 95% curcumin extract is poorly absorbed. The solution is to either consume whole turmeric or take an absorption enhanced curcumin extract such as BCM-95 or Longvida for example.

Read more about Longvida. https://vs-corp.com/longvida/

I would take 1 tablespoon of whole turmeric and mix it with some olive oil to make a slurry, let it sit for a few minutes and then add some plain yogurt to make it more palatable.

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meta analyses: curcumin and blood lipid levels

Post by jimmylegs » Mon Oct 08, 2018 4:05 am

A systematic review and meta-analysis of randomized controlled trials investigating the effects of curcumin on blood lipid levels (2014)
https://www.sciencedirect.com/science/a ... 1413002501

Summary
Background & aims
Curcumin is a polyphenolic natural compound with diverse and attractive biological activities. There has been in-vitro, preclinical and clinical evidence on the cardioprotective and lipid-lowering effects of curcumin. The present review aimed to systematically review and meta-analyze current clinical evidence on the effects of curcumin supplementation on blood lipids.

Methods
A comprehensive literature search in Medline, Scopus, AMED, Cochrane and clinical trial registry databases was performed to identify randomized controlled trials investigating the effect of curcumin on any component of serum lipid profile including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides. Meta-analysis of eligible studies was conducted using a random-effects approach.

Results
Five studies comprising 10 treatment arms (n = 133 in the curcumin and 90 in the control group) fulfilled the inclusion criteria. Meta-analysis of findings did not indicate a significant effect of curcumin on any of the lipid parameters. The estimated pooled mean changes (95% confidence interval) following curcumin supplementation were 8.97 (95% CI: −4.56 to 22.51) mg/dL (for total cholesterol; p = 0.19); 16.15 (−4.43 to 36.74) mg/dL (for LDL-C; p = 0.12); −0.59 (−1.66 to 0.49) mg/dL (for HDL-C; p = 0.28) and −1.29 (−9.05 to 6.48) mg/dL (for triglycerides; p = 0.75). In the same manner, subgroup analysis of studies on patients at cardiovascular risk did not indicate any significant effect of curcumin on circulating lipid levels. There was a significant heterogeneity for the impact of curcumin on total cholesterol, LDL-C and triglycerides but not HDL-C.

Conclusions
In light of the present meta-analysis, curcumin supplementation has apparently no effect on serum total cholesterol, LDL-C, triglycerides and HDL-C levels when considering heterogeneous populations. However, further randomized controlled trials with longer supplementation duration, and bioavailability-improved formulations of curcumin are warranted to be conducted in dyslipidemic subjects for a more robust assessment of the lipid-modulating properties of this phytochemical.
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Re: meta analyses: curcumin and blood lipid levels

Post by jimmylegs » Mon Oct 08, 2018 4:11 am

would be interesting to have a look at any particular inclusion criteria for this one, in comparison to the above

Lipid-modifying activity of curcuminoids: A systematic review and meta-analysis of randomized controlled trials (2017)
https://www.tandfonline.com/doi/abs/10. ... 17.1396201

ABSTRACT
Objective: The aim of this systematic review and meta-analysis was to determine and clarify the impact of curcuminoids on serum lipid levels. Methods: Randomized controlled trials (RCTs) investigating the effects of curcuminoids on plasma lipids were searched in PubMed-Medline, Scopus, Web of Science databases (from inception to April 3rd, 2017). A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on lipid concentrations. Results: A meta-analysis of 20 RCTs with 1427 participants suggested a significant decrease in plasma concentrations of triglycerides (WMD: −21.36 mg/dL, 95% CI: −32.18, −10.53, p < 0.001), and an elevation in plasma HDL-C levels (WMD: 1.42 mg/dL, 95% CI: 0.03, 2.81, p = 0.046), while plasma levels of LDL-C (WMD: −5.82 mg/dL, 95% CI: −15.80, 4.16, p = 0.253) and total cholesterol (WMD: −9.57 mg/dL, 95% CI: −20.89, 1.75, p = 0.098) were not altered. The effects of curcuminoids on lipids were not found to be dependent on the duration of supplementation. Conclusion: This meta-analysis has shown that curcuminoid therapy significantly reduces plasma triglycerides and increases HDL-C levels.
take control of your own health
pursue optimal self care at least as actively as a diagnosis
ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!

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