Truth comes out in wine.

Resveratrol

I don’t think I have previously written about resveratrol in connection with ADPKD but I have made copious notes about it over the last two years, indicating that it keeps popping up on my radar. This is maybe not surprising as there have been so many health claims for its benefits – it is reported to defeat Alzheimer’s, prevent heart attacks and correct hormone imbalance (that last one was this week, it is now being hailed as the answer to infertility, polycystic ovaries and even PMT).

I don’t propose to argue the benefits here, but I do want to bring to your attention a small paper and an editorial recently published concerning the effects of resveratrol on kidneys in rat models of ADPKD.
What is RESVERATROL?
It is a really difficult word to pronounce, my tongue prefers “reservatrol“. The name is derived from the fact that it is a RESorcinOL first found in the plant VERATRum album.

It is a chemical produced by a stressed plant, not all plants, mostly grapes, a few berries and boiled peanuts (who wouldn’t be stressed by being boiled – but I think the peanut already contains the chemical, boiling is just a way of extracting it). So it has a natural role as part of a plant’s defences.

It is particularly in the skin of grapes, so red wine, where the process of making it involves more contact with the grape skins, has more in it than white wine.

Research on potential health benefits began earnestly in the 1990s. If I recall correctly this was the decade when one day wine was good for you, the next it was carcinogenic and a week later red wine was on the table again – to be honest I never managed abstention!

In the following decade resveratrol was headlined as the explanation for the French paradox – the oddity that French people have batter cardiovascular health despite high intake of wine. We need to be very careful interpreting the research headlines from this era, in particular with respect to resveratrol: a professor from Connecticut who authored many of the papers on the topic was later discredited for falsification of data. While his actual papers have been withdrawn, they were cited and sometimes provided the basis for new papers so the field became very muddy.

Jump forwards ten years and we now have long lists of the molecular targets of resveratrol. There are many.

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So what is the connection with PKD?
The basic mechanisms involved in kidney damage in ADPKD are increased cell proliferation with alterations in cell polarity which leads to cyst formation and the cysts fill up due to enhanced fluid secretion and abnormal cell-matrix interactions. There are additional factors involved besides the two abnormal proteins pkd1 and pkd2, such as inflammation and macrophage infiltration of the tissues surrounding the cysts (see previous post on fibrosis).

Resveratrol was considered as a potential therapeutic agent in ADPKD because it has been shown to have anti-inflammatory, anti-oxidant and anti-fibrotic effects.

 
Ming Wu’s study:
The study was published this month in the journal Nephrology Dialysis Transplantation.  While you need a subscription  to access the full paper, it is also the subject of the editorial in the same issue, for which online access is free (2016 only)

They used Han:SPRD (Cy/+) rats – we have seen these before (see From Alpha to Omega post), they are a model for polycystic kidney disease but are not the same as human ADPKD. They are useful to study mechanisms but do not guarantee that the same effect will be seen in human ADPKD.

The rats were treated for five weeks with resveratrol at a dose of 200mg/kg/day. Results showed that levels of several significant inflammatory molecules were reduced, including monocyte chemoattractant protein-1 (MCP-1).

MCP-1 has previously been shown to correlate with the presence of high numbers of macrophages around the cysts and it has been identified in urine from patients with ADPKD. There is therefore some hope that if you can reduce levels of MCP-1, as the resveratrol seemed to do, then the macrophages would not be attracted to the area, there would be less epithelial cell proliferation and less growth in the cysts. This was in fact what they found – the rats treated had smaller kidney mass and smaller cyst volumes.

In the words of the editorial, resveratrol “looks promising”.

 

But (always) – resveratrol is thought to exert some effects through the sirtuins (silent information regulating proteins). Simply put, they suppress aging and cell destruction and so theoretically they may have an effect on cancerous growths. So although to date the benefits seem to outweigh any adverse effects, there is need for caution.

 

 

The bottom line:
Resveratrol is found in red wine, but you would need to drink several bottles to achieve the equivalent dosing of this study. It is available as a “herbal” food supplement but as with all supplements, there is no regulation to control manufacture and so the concentration of active resveratrol will vary in the various formulations. Also there is at the moment, no standard for recommending any particular dose. Resveratrol is another drug with pleiotropic effects on many pathways, which means identifying one that has a benefits in one disease is just the beginning of a long journey to safety as a therapeutic agent.

It is a really interesting branch of research where hopefully the potential benefit to so many areas will drive progress. This study had an additional element where the authors continued to study the effects of resveratrol on human PKD cells in culture and also in kidney development in Zebra fish – they are trying to identify mechanisms of action.  Now Zebra fish – they are fascinating, but thats another post entirely.

 

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Truth comes out in wine.

Pliny

 

 

 

 

 

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