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Resveratrol Restores Vision in Macular Degeneration Patients

resveratrol

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#1 cudBwrong

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Posted 10 June 2013 - 07:45 PM


https://www.ncbi.nlm...pubmed/23736827

"dramatic short-term anti-VEGF type effect including anatomic restoration of retinal structure"

Observation of human retinal remodeling in octogenarians with a resveratrol based nutritional supplement.

Abstract

Purpose: Rare spontaneous remissions from age-related macular degeneration (AMD) suggest the human retina has large regenerative capacity, even in advanced age. We present examples of robust improvement of retinal structure and function using an OTC oral resveratrol (RV) based nutritional supplement called Longevinex® or L/RV (circa 2004, Resveratrol Partners, LLC, Las Vegas, NV, USA). RV, a polyphenolic phytoalexin caloric-restriction mimic, induces hormesis at low doses with widespread beneficial effects on systemic health. RV alone inhibits neovascularization in the murine retina. Thus far, published evidence includes L/RV mitigation of experimentally induced murine cardiovascular reperfusion injury, amelioration of human atherosclerosis serum biomarkers in a human Japanese randomized placebo controlled trial, modulation of micro RNA 20b and 539 that control hypoxia-inducing-factor (HIF-1) and vascular endothelial growth factor (VEGF) genes in the murine heart (RV inhibited micro RNA20b 189-fold, L/RV 1366-fold). Little is known about the effects of L/RV on human ocular pathology. Methods: Absent FDA IRB approval, but with permission from our Chief of Staff and medical center IRB, L/RV is reserved for AMD patients, on a case-by-case compassionate care basis. Patients include those who progress on AREDS II type supplements, refuse intra-vitreal anti-VEGF injections or fail to respond to Lucentis®, Avastin® or Eylea®. Patients are clinically followed traditionally as well as with multi-spectral retinal imaging, visual acuity, contrast sensitivity, cone glare recovery and macular visual fields. Three cases are presented. Results: Observed dramatic short-term anti-VEGF type effect including anatomic restoration of retinal structure with a suggestion of improvement in choroidal blood flow by near IR multispectral imaging. The visual function improvement mirrors the effect seen anatomically. The effect is bilateral with the added benefit of better RPE function. Effects have lasted for one year or longer when taken daily, at which point one patient required initiation of anti-VEGF agents. Unanticipated systemic benefits were observed. Conclusions: Preliminary observations support previous publications in animals and humans. Restoration of structure and visual function in octogenarians with daily oral consumption of L/RV is documented. Applications include failure on AREDS II supplements, refusing or failing conventional anti-VEGF therapy, adjunct therapy to improve RPE function, and compassionate use in medically underserved or economically depressed third-world countries.

#2 cudBwrong

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Posted 10 June 2013 - 08:26 PM

This is a free full text article. A word of caution: the authors describe how they selected a dose level (100mg / day ) and describe hormesis, in which resveratrol may show harmful effects at higher doses. However, their source appears to be this paper:

http://www.ncbi.nlm....cles/PMC3016073

whose authors include Dipak K Das, who is involved in a controversy regarding the falsification of data.

This paper has not been retracted, but another paper by Das on the same subject, resveratrol and
hormesis, has been retracted by the publishing journal following notifications submitted by
the University of Connecticut:

http://www.ncbi.nlm....pubmed/18789672

I don't think these issues reflect upon the main findings regarding macular degeneration. It's only 3 cases, but
very interesting. The resveratrol used was a Longevinex formulation which includes additional supplements.

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#3 cudBwrong

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Posted 11 June 2013 - 03:51 AM

The authors cite 4 papers co-authored by Dipak Das. To the best of my knowledge, none of the cited papers have been retracted, but there are reports that 19 papers by Das have been retracted by the journals which published them:

http://retractionwat...ing-were-amiss/

I don't think that this has any bearing on the results observed in the AMD patients, and it may turn out that all of the results reported by Das and his co-authors withstand scrutiny and are replicated by other groups. However, given the controversy, it is wise to be cautious.

Edited by cudBwrong, 11 June 2013 - 03:54 AM.


#4 hav

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Posted 15 June 2013 - 07:22 PM

I read the full text twice and I can't seem to find mention of how they delivered the test substances, which are typically either powders or solids, by oral gavage. If they used a solvent, that could be a material omission.

Howard

#5 cudBwrong

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Posted 17 June 2013 - 01:19 PM

I read the full text twice and I can't seem to find mention of how they delivered the test substances, which are typically either powders or solids, by oral gavage. If they used a solvent, that could be a material omission.

Howard

Howard, I think you are referring to this paper:

http://www.ncbi.nlm....les/PMC3016073/

which seems to be the source of the comments about hormesis and the lower toxicity of Longevinex as compared with resveratrol. I agree that the methods description lacks important details. I am even more concerned that there is no description of the source of the so-called "resveratrol." How was it obtained, what was its purity, how was that verified?

This paper cites at least two other papers on similar topics, by some of the same authors, that now have been retracted:

http://www.sciencedi...891584908007119

http://www.ncbi.nlm....pubmed/18789672

These issues do not contradict the observations in the case reports on macular degeneration, but we should be very cautious about accepting findings published in retracted papers until those findings have been confirmed by independent groups.

#6 maxwatt

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Posted 17 June 2013 - 03:10 PM

Dipak Das had a close relationship with Long-ev-inex's owner, Bill S.a.a.r.d.i , and his papers consistently confirmed S.a.a.r.d.i.s' theories, and B.S's formulations. B.S. financially supported many of Das' studies. Not to accuse Mr. Professor Das of collusion or tailoring his findings to suit his sponsor, but that judgement appears to have been made by the University of Hartford where Das worked, and by the journals that published Das' work and therefore retracted them. No one knows which if any of Das' results are valid, which were falsified. It's a problem. Many of his results have not been replicated, and perhaps cannot be. Most researchers will not pursue negative findings, nor will journals publish them unless there are exceptional circumstances.

#7 niner

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Posted 18 June 2013 - 11:49 AM

This is a pretty important paper, if resveratrol actually has an impact in AMD. Lon-gev-in-ex is a defined product, in pill form, so the normal dosing route would be oral. It contains more than just resveratrol, so we don't really know what the active ingredient was. I haven't read the paper, but they must have said something about the dose. Das is not an author on this paper, and it looks like it came out of a different lab, so it's not reasonable to assume the work is tainted because they cited one of his non-retracted papers. The citation may not even be material to the work- sometimes a handful of references get added for "completeness", or because the author has a citation obsession.

#8 cudBwrong

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Posted 18 June 2013 - 12:47 PM

This is a pretty important paper, if resveratrol actually has an impact in AMD. Lon-gev-in-ex is a defined product, in pill form, so the normal dosing route would be oral. It contains more than just resveratrol, so we don't really know what the active ingredient was. I haven't read the paper, but they must have said something about the dose. Das is not an author on this paper, and it looks like it came out of a different lab, so it's not reasonable to assume the work is tainted because they cited one of his non-retracted papers. The citation may not even be material to the work- sometimes a handful of references get added for "completeness", or because the author has a citation obsession.

Let me clarify, because it's a little confusing. The paper in the original post (Richer et. al.) does not have Das as an author, although it cites 4 papers for which Das was a co-author. Any problems with the work done by Das have no significance for the case observations regarding the benefits of Longevinex in Age Related Macular Degeneration (AMD).

Howard and I were discussing one of the papers by Das which were cited by the Richer paper, and which seems to be the basis for a number of statements regarding the effects of different doses of reseveratrol and Longevinex on heart muscle. The claim in that paper, and in a now-retracted paper which it, in turn cites, is that resveratrol benefits heart muscle at lower doses, and injures it at higher doses, while Longevinex had a beneficial effect even at higher doses. This is the finding which, in my opinion, will be more convincing if it is replicated by other groups.

Richer and his team cited these results by Das when choosing their source of resveratrol, in the interest of patient safety. Their observations are independent of the quality of Das' work.

There is an open question whether the other ingredients in Longevinex are partially or completely responsible for the benefits seen in these patients.

There is other evidence that resveratrol, in itself, is beneficial for diseases of the retina. I have a retina disease, Mactel Type 2, which has a similar pathology to AMD. Resveratrol was effective in treating this in an animal model of Mactel. It was administered to a genetically modified mouse which spontaneously develops retina damage which resembles Mactel:

http://www.ncbi.nlm....pubmed/21282584

I'm taking resveratrol for this reason, in consultation with my physician. So far, my condition has stabilized, which is a good result, but it's not possible to say if resveratrol is helping me.
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#9 ClarkSims

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Posted 07 February 2016 - 11:58 PM

This is a pretty important paper, if resveratrol actually has an impact in AMD. Lon-gev-in-ex is a defined product, in pill form, so the normal dosing route would be oral. It contains more than just resveratrol, so we don't really know what the active ingredient was. I haven't read the paper, but they must have said something about the dose. Das is not an author on this paper, and it looks like it came out of a different lab, so it's not reasonable to assume the work is tainted because they cited one of his non-retracted papers. The citation may not even be material to the work- sometimes a handful of references get added for "completeness", or because the author has a citation obsession.

 

I looked into buying Longevinex, and all of the offerings were "new formulations"

http://store.longevi...gevinex-c2.aspx

 

I really wanted to buy the one described in the studies for AMD and longevinex.

 

Abstract: Background: Longevinex ® (L/RV) is a low dose hormetic over-the-counter (OTC)
oral resveratrol (RV) based matrix of red wine solids, vitamin D 3 and inositol hexaphosphate
(IP6) with established bioavailability

 

The group of researchers appear to have no connection with Dipak Das.  However this stud was funded by makers of Longevinex. The pattern of behaviour seems suspicious.

 

Are there any studies of resveratrrol and AMD that were not funded by Resveratrol Partners LCC?

 

Assuming the formulation used in this study no longer exists, is micronized resveratrol just more bioavailable than normal resveratrrol? I could just mix up my own formulation.

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#10 cudBwrong

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Posted 10 February 2016 - 12:36 AM

 

This is a pretty important paper, if resveratrol actually has an impact in AMD. Lon-gev-in-ex is a defined product, in pill form, so the normal dosing route would be oral. It contains more than just resveratrol, so we don't really know what the active ingredient was. I haven't read the paper, but they must have said something about the dose. Das is not an author on this paper, and it looks like it came out of a different lab, so it's not reasonable to assume the work is tainted because they cited one of his non-retracted papers. The citation may not even be material to the work- sometimes a handful of references get added for "completeness", or because the author has a citation obsession.

 

I looked into buying Longevinex, and all of the offerings were "new formulations"

http://store.longevi...gevinex-c2.aspx

 

I really wanted to buy the one described in the studies for AMD and longevinex.

 

Abstract: Background: Longevinex ® (L/RV) is a low dose hormetic over-the-counter (OTC)
oral resveratrol (RV) based matrix of red wine solids, vitamin D 3 and inositol hexaphosphate
(IP6) with established bioavailability

 

The group of researchers appear to have no connection with Dipak Das.  However this stud was funded by makers of Longevinex. The pattern of behaviour seems suspicious.

 

Are there any studies of resveratrrol and AMD that were not funded by Resveratrol Partners LCC?

 

Assuming the formulation used in this study no longer exists, is micronized resveratrol just more bioavailable than normal resveratrrol? I could just mix up my own formulation.

 

Hi, Clark

 

The study you attached is a follow up to the original paper I posted.

 

Regarding the Dipak Das issue, it is unfortunate.  Mr. Das is no longer alive.  I corresponded with the principal investigator of this study, and for what it's worth, I think he is on the level.  He was aware of the issues surrounding Das at the time, and his lab got some funding from the manufacturer, but I think the results of this study are as reported -- just my view here.  It's a case report, 3 patients, basically an anecdote, but as they say, the plural of anecdote is data.  I believe the facts are what they are.

 

I accessed the Longevinex website around the time of the original report, and I recall that it had 4 major components:  resveratrol, quercetin, phytic acid, and vitamin D.  My view, based on other evidence, is that the first 2 are particularly important.  There is some evidence that they are particularly effective in combination:

 

http://www.ncbi.nlm....pubmed/20108046

 

Quercetin may improve the bioavailability of resveratrol:

 

http://www.ncbi.nlm....pubmed/11055264

 

Many resveratrol formulations are micronized to improve absorption.  A high purity product is important.

 

Piperine, an ingredient of black pepper, significantly improves resveratrol bioavailability:

 

http://www.ncbi.nlm....les/PMC3634921/

 

http://onlinelibrary...100117/abstract

 

For what it's worth, I have a (different) disease of the retina (Mactel 2) diagnosed 5 years ago.  Resveratrol and quercetin are 2 of my mainstays.  My retina doc says "You are on the right track.  Keep taking everything you are taking."  My disease has had no progression since diagnosis, the best possible result.  Mactel moves slowly, so this could be a coincidence, but on a risk/reward basis, I'll keep taking my pills.


 


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