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I'm in the process of sourcing some  italian wines with hi content of phenolic compounds. Since there is little literature, and little satisfactory, I'm going to proceed empirically, that is, based upon taste. Astringent taste in hi-quality wines is probably a measure of the concentration of phenolic compounds. Also, I have some hints, like the Cannonau Sardinian wine is suggested by Luigi Fontana. the quality I found in the local supermarket is not so great, so I'm going to try the locally fermented Montepulciano d'Abruzzo variety, which is pretty astringent and strong-tasting. Usually the good varieties are priced at about 20 US$ per 750 ml bottle and upward. I'll start asking people around. 

Strong and astringent taste is often correlated to a high presence of tannins, phenolic compounds and other beneficial phytochemicals, as my personal experience goes and how the opinions in thiis forum seem to agree. The absence of deleterious compounds due to degradation is gauranteed by the high quality and cost of the product. 

Wine in this context becomes a medicine.

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Michael Rae has written elsewhere:

 

Provinols: the only authentic red wine concentrate, which I would take if I could find if I could find the darned stuff. Unlike the shaky-to-begin-with-and-now-disproven resveratrol hype, there is a quite solid body of epidemiological evidence of an association between a couple of glasses of wine a day and lower risk of a range of adverse outcomes, including total mortality and dementia. The epidemiology clearly indicates a U-shaped dose-response curve for alcohol consumption and heart disease, with the best outcomes associated with 1-3 drinks/d, and this extends to total mortality in meta-analysis(19); but when broken down into type of alcohol consumed, only wine lowers total mortality and dementia: beer or spirits lower CVD mortality, with no effect on total. (No, despite the use of these findings as a justification for resveratrol supplements, there is no epidemiological evidence favoring red over white). The benefits for total mortality reach a nadir at
ira60012f2.png
Figure 1. Relative risk of total mortality (95% confidence interval) and alcohol intake extracted from 56 curves using fixed- and random-effects models. From (19).

 

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Wine consumption vs. total mortality. From (38).

However, my working hypothesis is that the climbing risk is due to the toxicity of alcohol per se, and that additional benefits might be available from higher intake of the component(s) of wine responsible for these benefits, without the extra Calories and toxicity of drinking the stuff. However, we don't know which component(s) of wine exert these effects, so we should aim for a supplement that is a direct concentrate of the same spectrum of bioactives in actual, fermented wine -- ie, not just resveratrol, nor the grape-seed and/or -skin extract that is often mislabeled "wine extract," and whose polyphenol mix is actually quite different from that in wine, due to complexation and biotransformation that the grapes undergo during fermentation. Seppic in France has done a great deal of work in characterizing these, and still the surface is only barely scratched and we don't know what might do what.

Therefore, I went looking for a genuine concentrate of actual red wine that did not rely on high temperature or extraneous chemicals which might also alter the original mix, and which did not come from China or another country with high levels of industrial contaminants or shady business practices.

I first hit on Provinols, which is a pioneering product in this field, but unfortunately it is damned near impossible to get in the Americas, except in low doses and mixed in with other junk. (Europeans and Turks may be able to get it, however). I was at one time convinced of the authenticity of a product called Wine Rx, but they subsequently failed to document their claims on composition, and moreover, it seems to go vinegary and weird in well less than a year -- not surprising perhaps granted that it was only a 50% extract. So, I wait glumly for the Real Deal.                       

http://www.longecity.org/forum/topic/54272-another-day-another-pill-2012-supplement-regimen/

 

I was wondering if Michael R. or any one else had any new thoughts on Provinols or similar red wine extracts.
 

Obtained by extraction from real wine, PROVINOLS™ has the particularity to have the same polyphenols profile as the red wine it is extracted from. It contains 70% polyphenols. It was developed to provide the benefits of the “French Paradox” through nutritional products and without alcohol consumption.

 

https://www.seppic.com/provinolstm-0

 

I bought this product once:

 

Best French Red Wine Extract contains BioVin Advanced, A French Red Wine extract made from whole red wine grapes. BioVin Advanced contains 5% red wine trans-resveratrol and 30-35% red wine polyphenols, including anthocyanins and other flavonoids.

 

But it appears to be an extract from red wine grapes, not red wine itself.     I used to use it spike some Crimean wine.

 

 

Oh look!  A hot-off-the-press Provinols rat study:

 

Paradoxical Effect of Nonalcoholic Red Wine Polyphenol Extract, Provinols™, in the Regulation of Cyclooxygenases in Vessels from Zucker Fatty Rats (fa/fa)

 

https://www.hindawi.com/journals/omcl/2017/8536910/

 

 

Cf. https://www.degruyter.com/view/j/sjecr.2016.17.issue-2/sjecr-2015-0060/sjecr-2015-0060.xml

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0005557

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A combination of Ursolic acid (appel skins, rosemary) and curcumin seems to be a powerful anti-Pca agent.

This is a very good paper which investigates synergistic combinations of Ursolic acid, curcumin and resveratrol. The issue of combinations has already been discussed in the context of curcumin and piperine.

 

https://www.nature.com/articles/s41698-017-0024-z

 

 

 

 

In conclusion, an initial screening approach has been developed to identify potential synergistic phytochemical combinations with chemopreventive/therapeutic efficacy for inhibiting growth of PCa and possibly other cancer cells. The ability of combinations to synergistically inhibit tumor growth was linked to synergistic changes in glutamine metabolism, the associated modulation of STAT3/Src, mTORC1 and AMPK signaling, and induction of apoptosis.
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Ursolic acid. From examine.com:

 

 

Major sources (Food products or common supplements) include:

 

  •  

 

620px-Ursolic_acid.svg.png

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Sibiriak, thanks for the reference to MR's post. Provinol sounds promising, although not very well-known nor easily found.

 

In the meanwhile, from the curves posted by MR 100 ml of wine daily seems to be the optimum amount. I drink much less than that, should commit to be consistent.

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Mccoy,  Michael R. hypothesizes that "the climbing risk is due to the toxicity of alcohol per se, and that additional benefits might be available from higher intake of the component(s) of wine responsible for these benefits, without the extra Calories and toxicity of drinking the stuff."

 

Is it possible to remove alcohol from wine (heating it up, or?) without damaging the valuable polyphenols?

 

https://winemakermag.com/962-i-m-interested-in-cold-filtering-to-obtain-alcohol-free-wine

 

Spinning cone technology

 

http://www.frewines.com/fre-info/our-process

After harvest, our winemakers carefully craft each wine using traditional methods. Once the desired flavor, texture and balance is reached, we use state-of-the-art spinning cone technology to remove the alcohol while preserving delicate aromas and flavors. The alcohol-removed wine is then bottled until it makes its way to a glass near you!

 

http://edenvale.com.au/blog/How-do-you-remove-the-alcohol-from-the-wine

Spinning Cone Column (SCC) is a highly efficient counter-current liquid-gas contact device.The SCC is unique in its use of gentle mechanical forces to enhance inter-phase contact. This allows efficient and rapid separation of volatile compounds from their host material. The unique design of the SCC enables it to process clear liquids and viscous products containing high levels of suspended solids. The Spinning Cone Column is widely used as an aroma recovery or flavour management device.

 

[see graphic]

 

Wine is fed into the top of the spinning cone column (a vertical cylinder roughly 40″ in diameter and 13′ in height) and flows down over a series of alternating stationary and rotary metal cones. Centrifugal force transforms the wine into a thin liquid film, which is contacted by ascending nitrogen gas fed into the bottom of the cone.  The nitrogen acts as a carrier to extract the volatilized aroma and flavor compounds from the wine. These essences are then condensed, separated and safeguarded while the liquid is run through the cone again, at slightly higher temperatures, to remove the alcohol. Then they are reintroduced to the dealcoholized wine and blended with unfermented varietal grape juice to create a beverage with less than 0.3% alcohol by volume.

 

The spinning cone process is superior to other alcohol-removal systems, such as steam distillation and reverse osmosis (also known as membrane filtration) for two reasons. First, it protects the delicate aroma and flavor essences by removing them, at relatively low temperatures, prior to alcohol removal. Both steam distillation and reverse osmosis are single-stage systems in which wine aromas and flavors are degraded through exposure to either the heat or high pressures employed to remove the alcohol. Second, the spinning cone, unlike reverse osmosis, does not concentrate the residual base liquid to the extent that it must be re-diluted with water.

 

I wonder if any such non-alcoholic wines could have the same health benefits as the real McCoy.  :Dxyz

 

(Yes, Google is my friend.) 

 

Effects of red wine polyphenols and alcohol on glucose metabolism and the lipid profile: A randomized clinical trial

https://www.researchgate.net/publication/230807792_Effects_of_red_wine_polyphenols_and_alcohol_on_glucose_metabolism_and_the_lipid_profile_A_randomized_clinical_trial

 

Background & aims: Epidemiological data suggest that moderate red wine consumption reduces cardiovascular mortality and the incidence of diabetes. However, whether these effects are due to ethanol or to non-alcoholic components of red wine still remains unknown. The aim of the present study was to compare the effects of moderate consumption of red wine, dealcoholized red wine, and gin on glucose metabolism and the lipid profile.

 

Methods: Sixty-seven men at high cardiovascular risk were randomized in a crossover trial. After a run-in period, all received each of red wine (30 g alcohol/d), the equivalent amount of dealcoholized red wine, and gin (30 g alcohol/d) for 4 week periods, in a randomized order. Fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), plasma lipoproteins, apolipoproteins and adipokines were determined at baseline and after each intervention.

 

Results: Fasting glucose remained constant throughout the study, while mean adjusted plasma insulin and HOMA-IR decreased after red wine and dealcoholized red wine. HDL cholesterol, Apolipoprotein A-I and A-II increased after red wine and gin. Lipoprotein(a) decreased after the red wine intervention.

 

Conclusions: These results support a beneficial effect of the non-alcoholic fraction of red wine (mainly polyphenols) on insulin resistance, conferring greater protective effects on cardiovascular disease to red wine than other alcoholic beverages.
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This study raised some concerns about ursolic acid supplementation:

 

Atherosclerosis. 2011 Dec;219(2):402-8. doi: 10.1016/j.atherosclerosis.2011.05.025. Epub 2011 Jun 23.
 

Ursolic acid causes DNA-damage, p53-mediated, mitochondria- and caspase-dependent human endothelial cell apoptosis, and accelerates atherosclerotic plaque formation in vivo.

PMID:21703625

 

Quote

Abstract

Objective: The plant derived triterpene ursolic acid (UA) has been intensively studied in the past; mainly as an anti-cancer compound and for its cardiovascular protective properties. Based on the controversy of reports suggesting anti-angiogenic and cytotoxic effects of UA on one side and cardiovascular and endothelial protective effects on the other side, we decided to assess UA effects on primary human endothelial cells in vitro and atherosclerotic plaque formation in vivo.

Methods and results: Our in vitro analyses clearly show that UA inhibits endothelial proliferation and is a potent inducer of endothelial cell death. UA causes DNA-damage, followed by the activation of a p53-, BAK-, and caspase-dependent cell-death pathway.

Oral application of UA in APO E knockout mice potently stimulated atherosclerotic plaque formation in vivo, which was correlated with decreased serum levels of the athero-protective cytokine IL-5.

Conclusions: Due the potent endothelial cell death inducing activity of UA, a systemic application of UA in the treatment of cardiovascular diseases seems unfavourable. UA as an anti-angiogenesis, anti-cancer and - locally applied - cardiovascular drug may be helpful. The DNA damaging activity of UA may however constitute a serious problem.

 

Ursolic Acid—A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities (2015)

 

Quote

The impact of ursolic acid on atherosclerosis is the subject of dispute amongst scientists since some studies show potentially beneficial effects while others show potentially negative effects [139].

For example Ullevig et al. [140] reported the inhibition of monocyte dysfunction and the slowing down of accelerated atherosclerosis in diabetic mice, while Messner et al. [141] described the stimulation of atherosclerotic plaque formation in mice administered with UA.

The potentially harmful effect of UA intake has been presented by Kim et al. [142]. They discovered that this triterpene is capable to make platelets more susceptible to aggregation, and they should be used with caution by people with a predisposition to cardiovascular events.

 

Btw,  here's the ursolic acid/ brown fat study Dean P. brought up in the "Cold Exposure" thread:

Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039332

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mccoy: This is a very good paper which investigates synergistic combinations of Ursolic acid, curcumin and resveratrol.

 

https://www.nature.com/articles/s41698-017-0024-z

 

In this study, a high-throughput screening approach was used to screen a natural compound library (NCL) and evaluate the efficacy of phytochemicals, when administered alone and in combination of two compounds using murine and human cell lines. The effect of the most promising compounds (UA, CUR and RES) were tested in vivo in a murine allograft model of PCa, as individual and combination treatments.

Thirteen days after injection of spheroids, treatment with the natural compounds was started by switching animals to semipurified AIN76A-based diets containing 1.0% CUR, 0.2% UA, 0.5% RES or their combinations (all ad libitum)

 

There are huge bioavailability issues that limit the practical applicability of  such in vitro /non-human in vivo study results.   I'm most familiar with curcumin, having done a good deal of research on it--the bioavailability and bioactivity issues are extraordinarily complex and clouded by biased research.

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I wonder if any such non-alcoholic wines could have the same health benefits as the real McCoy.  :Dxyz

 

Probably so, the drawback here is that the spinning column method appears to be of very limited use. That producer has no sellers in Italy. Using wine for cooking lets alcohol evaporate, so that may be a way, with unknown effects on the phenolic compound (many of 'em are insensitive to temperature though). I used red wine recently to cook red cabbage and red onions, a very red and phytochemicals-rich dish.

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I found this description of Biovin Advanced Red Wine Extract at several sites:
 

BioVin Advanced is a red wine extract manufactured in France from premium red grapes abundant in polyphenols and resveratrol. The grapes are fermented into wine, which then undergoes filtration to remove any impurities. The final product is purely extracted and washed with grain alcohol before the alcohol is evaporated, resulting in a potent concentrate.

 

Okay, not on par with the tantalizing, mystical, MR-approved -but -unobtainable Provinols, but perhaps worth considering.

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There are huge bioavailability issues that limit the practical applicability of  such in vitro /non-human in vivo study results.   I'm most familiar with curcumin, having done a good deal of research on it--the bioavailability and bioactivity issues are extraordinarily complex and clouded by biased research.

 

 

So now what's your practical position on curcumin? I use both the fresh root and the powdered root, sometimes raw sometimes cooked, always together with  abundant black pepper.

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Re ursolic acid: like in many cases, supplementation may not be so effective or may even given problems like in the article you cited.

Apple peels seem to be the major source of UA, I'm going to wait for the apples season and then start trying the combo UA+CUR; I'll have to think about what to do with the pulp of the apples.

 

This is an interesting reference on triterpenes, which includes the ursane family, of which the UA is part. there is a table with the content of various triterpenes and UA in foods. Apple peels contain 1.45% weight in dry matter. The richest is rosemary, whose leaves contain 2.95%. But of course it's easy to eat 50 g of apple peels, whereas the equivalent in UA, 25 g of rosemary, is not an easy serving to gulp down.

 

http://www.mdpi.com/1420-3049/14/6/2016/pdf

 

I remember about the coffee diterpenes kafestol and kawheol, I'm satisfied that also triterpenes exhibit anti-cancer properties. I just found out that tetraterpenes include lycopene which is a powerful anti-Pca phytochemical. And carotenoids.

Monoterpenes include limonene and pinene (found in pine nuts). 

 

Terpenoids

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Mccoy,  in a nutshell (avoiding a long post!),   I've been taking variations of:

 

 1) Turmeric  powder (personal preference:  heat in a little oil,  possibly add pepper/piperine --there are arguments pro/con on that-- and/or quercetin, or take quercetin beforehand, and mix into kefir to drink.)

 

2) A curcumin supplement designed for enhanced bioavailability,  such as Longvida or Meriva, which are quite different from each other.    That's a topic in itself.  

 

3) A curcumin supplement which contains concentrated curcumin + turmeric essential oils/turmerones.

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From that article:

 

Lansky et al. [78] reported that ellagic acid, caffeic acid, luteolin, and punicic acid that are found in substantial amounts in the peels, PJ, and PSO of the pomegranate fruit reduced the invasive potential of PC-3 cells. A supradditive inhibition in PC-3 cell invasion was observed when caffeic acid, luteolin, and punicic acid were equally combined at the same gross dose when compared to individual agents

 

I stumbled across this description of Lansky's work:

 

Another Israeli, Dr. Ephraim Lansky has focused on pomegranates effect on cancer. You may recall earlier newsletters in which I extolled the potential role of raspberries in cancer treatment because they contained large amounts of ellagic acid. In another letter I mentioned Lansky's work because pomegranates turned out to be an excellent source of ellagic acid. It isn't that simple. Pomegranates contain a number of different chemicals which play a roll besides ellagic acid. Pomegranate polyphenols act as aromatase inhibitors blocking the synthesis of estrogen. They are able to inhibit the growth of breast cancer cells. Lansky has tried various extracts: the oil from the seeds, juice, wine and an extract from the pericarp (the thick skin that surrounds the seeds).

 

In Lansky's work, the juice was only minimally effective, but fermentation (pomegranate wine) liberated the active chemicals making it very effective. [6] He is behind the sale of a fermented pomegranate extract called Cardiogranate. Cardiogranate is a mixture of concentrated fermented pomegranate juice, watery extract of organically grown pomegranate peels, concentrated fresh pomegranate juice and honey. It is designed to deliver the antioxidant protective effects of a daily glass of pomegranate juice in just two teaspoons of elixir.

http://www.denvernaturopathic.com/news/pomegranate.html

 

I don't think Lanksy's pomegranate elixir is currently available, but a product called "Cardio Pom"  might be which contains extracts of fermented pomegranate juice, leaves, rind and seeds in encapsulated powder form.

 

Otherwise, there are many other pomegranate extracts on the market,  some just from the seeds, others from the whole fruit, and some also containing extracts from the flowers and oil from the seeds.

 

Of course, you can just eat the fruit or drink the juice, if you can get enough pomegranates and don't mind the sugar content.

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Updated list of PC topics

  • Exercise
  • Regular sex
  • Vegan diet
  • Avoiding dairy products, animal fats
  • Moderating IGF-1 (by various means)
  • Moderating  mTOR (by various means)
  • Moderating  insulin (by various means)
  • Soy, flaxseeds/ isoflavones/phytoestrogens/lignans
  • Turmeric/curcumin
  • Coffee/caffeine
  • Cayenne pepper/capsaicin
  • Green Tea
  • Saw palmetto
  • Vitamin D
  • Beta carotenoids
  • Lycopene
  • Sulforaphane
  • Red wine/ grapes/resveratrol
  • Apple peels/ursolic Acid
  • Pomegranate

 

Possible additional PC topics:

  • Selenium
  • Zinc
  • Boron
  • Aspirin
  • Probiotics (lactobacilli )
  • Omega 3s
  • I3C, DIM, and PEITC from cruciferous vegetables ( sulforaphane already mentioned)
  • Various berries:   blackcurrants,  black raspberries etc.
  • Astaxanthin
  • Garlic/onions
  • Avoiding excessive choline
  • Avoiding folic acid supplementation (vs folate)
  • Avoiding fried foods (n.s.s.!)
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Re: Boron. Pretty rich in nuts. It may be yet another cause of the many benefits of nuts consumption. Also, a 200g avocado would provide the suggested optimum amount of 3 mg/d.

Raisins according to Naghii et al. have the highest content measured (4.5 % in weight). I'll keep adding rasinins galore to my daily ration of soaked muesli.

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The amount of Boron will vary of course according to springs and aquifers geology, barring external pollution sources.

 

Contents for mineral bottled waters are usually available, in Italy many popular brands have a content which ranges from 500 to 1000 mg/liters, which is pretty good.

 

I don't know if tapwater analyses are public, I'm going to search. However, tapwater is not necessarily more controlled than bottled water.

A few years ago it was discovered that our local tapwater network drew from a water well located near an highly polluted illegal dump from a chemical manufacturer which started producing mustard gas in 1920 and made all kinds of toxyc chemicals!

It turned out that local politicians knew that and diluted the water.

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