written by reader The Resveratrol Bust, the ARB Scare, and Other Short Takes

by Michael Jorrin, "Doc Gumshoe" | August 13, 2013 11:17 am

Another missive from our favorite medical maven, Doc Gumshoe

The Resveratrol[1] Bust

Disappointing, but unsurprising, I say. At this point I’m willing to stake my bet that the wonderful promise of resveratrol isn’t going to pan out. What’s resveratrol? Let’s take a little journey back in our time machine

About Resveratrol

It goes back at least 70 years, to the discovery by Japanese investigators of the active ingredient in a plant used in some traditional healing practices, the white hellebore. It was then learned that grape vines, when attacked by a particular fungus, also secreted this substance, which was named resveratrol. It was speculated that resveratrol might be a natural defense agent for the grape vines, and protect them from rot and blight. And, who knows, it might be good for humans as well.

The French Paradox

Now, also going back quite a few years, we Americans began to look enviously across the pond at the French and the Italians. We were worried about cholesterol[2], and the Word was that we needed to cut way back on butter and eggs[3] and bacon and well-marbled steaks. But those lucky French didn’t seem to fret too much about all those cholesterol-laden foods, and it didn’t seem to hurt them a whole lot. You would have thought they would be turning up daisies, but no, they enjoyed their filet mignon with sauce Bearnaise (butter, egg yolks, a splash of tarragon vinegar). Might it be because they washed it down with copious goblets of Chateau Margaux? In any case, the French had much lower heart disease rates than we did, and there had to be some reason for it.

In fact, there were beginning to be pretty rigorous studies that seemed to point to a clear benefit from consuming alcoholic beverages, especially in terms of heart disease and cardiovascular mortality. Not that those studies should have been all that surprising either!

Let me digress for a moment. Lots and lots of doctors knew that moderate alcohol consumption was, on the whole, beneficial. (Note, whenever I mention alcohol consumption, in this blog or anywhere else, please assume that there’s an autocorrect feature that inserts the word “moderate” in front of that phrase.) There was an English physician in the 18th century by the name of Anstey who observed that among his patients the drinkers outlived the teetotalers by a comfortable margin, and he proposed a rule – a drink before dinner and a couple of glasses of wine with dinner – as a formula for a long life.

The studies I’m talking about began hitting the peer-reviewed medical journals in the 1970s, and in 1996 there was a big review in the British Medical Journal that more or less clinched the case for moderate alcohol consumption. Overall, the studies this review cited concluded that drinking alcoholic beverages, mostly wine, lowered heart disease risk by about 30%.

However, the mainstream medical establishment was not about to recommend alcoholic beverages to ward off heart disease. Alcohol – excessive alcohol – was known to cause all manner of health problems, not even counting all the other problems associated with alcohol. So it had to be something else!

The Resveratrol Promise

Might it be resveratrol? If it protected grape vines from rot and blight, might it not have beneficial effects in humans? From my perspective, as an initial assumption, that was quite reasonable. After all, as I said in a previous offering, many, many natural substances are the source of our most valuable drugs – and by drugs, I mean substances that we take that have curative powers. Also, resveratrol is present in red wine, and red wine is what the French and Italians mostly drink.

So they did tests in laboratory animals, mostly mice. They gave mice the mouse equivalent of filet mignon with Sauce Bearnaise, and, predictably, the mice became obese. Then they gave the mice resveratrol, and the obese mice that got resveratrol survived longer than the ones that didn’t get resveratrol.

At this point the researchers began to get very, very cheerful. Down the road, perhaps, here was a drug that would not only counteract the adverse effects of the American cholesterol-laden diet[4], but also, possibly, increase longevity. If this drug got approved, not only would it be hugely beneficial for lots of people, but the developers would reap unimaginable gains.

A little problem with these tests in mice, however, was that the smallest amount of resveratrol that had any beneficial effect in mice was many, many times larger than the amount of resveratrol in the amount of wine that any human being could possibly drink in a day. To get the amount of resveratrol equivalent to the lowest effective daily dose of resveratrol in the mouse studies, a person would have to drink 60 liters of wine per day, and in some mouse studies, the daily resveratrol dose was equivalent to 900 liters of wine. Impractical, to say the least!

That should have made it pretty clear that it wasn’t the resveratrol in the wine that was counteracting the evil effects of the French diet. But that didn’t stop the research from continuing. The pot of gold[5] at the end of the rainbow beckoned.

The Resveratrol Promise Fades

Unfortunately, when they got to studies of resveratrol in humans, the golden promise all but vanished. Here’s a really quick summary of three clinical trials:

That third study really put the kibosh on resveratrol. The studies that showed no benefit they could swallow, and keep looking, hoping that more studies would detect some benefit eventually. But a study in which resveratrol nullified the very real benefits of exercise is hard to get around.

So, if it’s not resveratrol, might it, after all, be the alcohol in the wine that’s producing those benefits?

The Bona Fide Benefits of Alcohol

Just you won’t think that I’m pushing my own agenda, here are some excerpts from a publication of the Harvard School of Public Health:

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Possible Health Benefits of Alcohol<

What are some of the possible health benefits associated with moderate alcohol consumption?

Cardiovascular Disease

More than 100 prospective studies show an inverse association between moderate drinking and risk of heart attack, ischemic (clot-caused) stroke, peripheral vascular disease, sudden cardiac death, and death from all cardiovascular causes. The effect is fairly consistent, corresponding to a 25 percent to 40 percent reduction in risk.

Beyond the Heart…

The idea that moderate drinking protects against cardiovascular disease[8] makes sense biologically and scientifically. Moderate amounts of alcohol raise levels of high-density lipoprotein (HDL, or “good” cholesterol), and higher HDL levels are associated with greater protection against heart disease. Moderate alcohol consumption has also been linked with beneficial changes ranging from better sensitivity to insulin to improvements in factors that influence blood clotting, such as tissue type plasminogen activator, fibrinogen, clotting factor VII, and von Willebrand factor. Such changes would tend to prevent the formation of small blood clots that can block arteries in the heart, neck, and brain, the ultimate cause of many heart attacks and the most common kind of stroke.

So it’s not the red stuff in the wine, it’s the ethanol[9] that confers those benefits. I need to add here, so that I don’t induce a dash to your local Rosie O’Grady’s, that “moderate alcohol consumption” is defined as two drinks per day for men and one drink per day for women; unfair some of you will say, but it’s based mostly on body weight, men being bigger and bulkier than women and thus have more body fluids for the alcohol to be distributed through. One drink is calculated as five ounces of wine or 12 ounces of beer or a jigger (an ounce and a half) of distilled spirits.

The J-Curve

That two drinks per day is actually the bottom of a J-curve. If we plot cardiovascular events (heart attacks, strokes, other serious cardiac events needing hospitalization) starting at its incidence in teetotalers, and then go on to measure its incidence in moderate drinkers, we find that this incidence is quite a bit lower in those moderate drinkers. But as consumption rises beyond the optimal two drinks per day point, the curve starts going up again, and by the time we get to about four drinks per day, it’s right back up to the rate for teetotalers, and it goes up from there. So the people who warn about the dangers of excessive alcohol consumption are right, of course, but it doesn’t become really excessive – i.e., more dangerous than being a teetotaler – until we get past that four drinks a day mark.

All that being said, we shouldn’t totally write off resveratrol. There’s at least a possibility that it may confer some benefit in other health-related areas, such as preventing osteoporosis and mimicking some of the benefits of a really strict diet. So far, not proven, but we’ll see.

And now, about something completely different …

The ARB Scare

This surfaced about two months ago, and the reverberations have been bouncing around in the medical community as well as among concerned patients. The scary possibility is that angiotensin receptor blockers, known as ARBs, might possibly “cause” an increase in cancers.

ARBs are antihypertensive, or blood-pressure lowering drugs. The appeared on the market about 15 years ago, and they have become a very widely-used and successful drug class. Drugs in this category are:

Atacand (candesartan), from AstraZeneca (AZN)[10]

Avapro (irbesartan), from Sanofi (SNY)[11]

Benicar (olmesartan), from Daiichi Sankyo (4568 Tokyo)

Cozaar (losartan), from Merck (MRK)[12]

Diovan (valsartan), from Novartis (NVS)[13]

Micardis (telmisartan), from Boehringer Ingelheim[14] (BING.GR)

ARBs lower blood pressure by inhibiting the renin-angiotensin system (RAS), which affects both heart rate and peripheral arterial resistance – the squeezing pressure of arteries on the blood. The specific messenger that triggers this blood pressure increase is angiotensin 2, and ARBs block the receptors for this messenger by occupying the receptor sites so that the angiotensin 2 can’t link up with the receptor.

A previous category of drugs that did more or less the same thing were the ACE (angiotensin-converting enzyme) inhibitors, which interfered with the action of the enzyme that converted the inactive form of angiotensin into the active angiotensin 2. ACE inhibitors work quite well, but they shouldn’t be used in people with any kind of respiratory problems such as asthma, while ARBs do not have that issue. Most high blood pressure drugs have issues of one kind or another, and ARBs seem, so far, to have fewer. That explains why, at a recent meeting of the American College of Cardiology, when members were asked what antihypertensive drugs they would prescribe for themselves or a family member, the winning category was ARBs.

The possibility that ARBs might be associated with increases in cancer risk was raised by a study published in Lancet Oncology back in 2010. This was a meta-analysis by Dr Ilke Sipahi of clinical trials with ARBs. The conclusions of this meta-analysis were that the risk of new cancers in the 61,590 patients in the five trials they analyzed increased from 6.0% in patients who did not take ARBs to 7.2% in patients who did take ARBs. The only specific cancer that was significantly higher in patients taking ARBs was lung cancer[15], with an incidence of 0.9% compared to 0.7% in patients not taking ARBs. No significant differences in cancer deaths were found in this study.

The brouhaha got started when a regulator at the FDA[16], Dr Thomas A. Marciniak, went against the directions of his bosses, arguing that warnings about the safety of ARBs should be make known to the public. Marciniak, on his own initiative, combed through the immense amount of data submitted to the FDA by the pharmaceutical companies, and concluded that ARBs increased lung cancer risks by about 24%. Officially, the FDA doesn’t agree, and neither do European regulatory agencies.

What could account for these huge differences?

At this time, nobody knows how Marciniak did his analysis. Dr Ellis Unger, the FDA chief of the drug evaluation division, suggests that the data used by Marciniak includes a large number of patient-reported events, collected as part of post-marketing data, many of which could be interpreted as new cancers, but which have not been independently investigated. ARBs have been in wide use for 15 years, have been studied in at least 25 clinical trials, and only in this instance is there a suggestion of cancer risk.

An interesting comment on this issue comes from Dr Henry Black, past President of the American Society of Hypertension. He notes, first, that there’s no mechanism of action whereby blocking the angiotensin 2 receptor could stimulate cancer cell growth. He points out that in the immense quantity of pre-clinical studies in animals, no increase in tumor growth was detected – otherwise, drug development would have stopped cold.

But more to the point, he questions the validity of the Sipahi meta-analysis. None of the studies in the meta-analysis by themselves attained statistical significance for the increase in cancers, and almost all of the increase came from two of the studies, both of which used telmisartan (Micardis). Overall, 85.7% of the patients in the meta-analysis were on telmisartan, raising serious questions about the legitimacy of generalizing the conclusions of this meta-analysis to the entire class of drugs.

Dr Black also raises a serious point about the potential for harm. Patients pick up these scary findings (as reported in the media, frequently with an alarmist slant), and decide to stop taking their medications, with possibly serious consequences. His conclusion was that the study was “very irresponsible and junk science.”

None of this decides the issue one way or another. The possibility cannot be ruled out that there is a cancer risk associated with ARBs, albeit a small one – the difference in incidence of new cancers reported in the Sipahi study was 1.2 percentage points, and of lung cancers, 0.2 percentage points. Not nothing, but not a whole lot. If I had hypertension[17], would I take an ARB? Probably yes, but I might pick one of the other ones rather than telmisartan.

This reminds me of the farrago in relation to the Women’s Health Initiative a few years ago, when a tiny – really tiny! – increase in the incidence of heart attacks occurring in women taking hormone replacement therapy (HRT) was trumpeted as a colossal increase in heart attack risk. The real difference was that in women on HRT, there were 37 heart attacks per 10,000 patient-years, while in women not on HRT, there were 30 heart attacks per 10,000 patient-years. The difference in absolute risk was less than 0.1%, but this was released to the press as a difference in relative risk of 23%.

A Bit More About Salt

Several readers have asked questions or commented about the issue of salt in our diets. One reader said, wasn’t it really the sodium[18] that should be measured and monitored, and not the salt. Yes, sodium ions play a vital role in a great number of physiologic processes, including muscle contractions. However, sodium enters and exits our bodies in salt (sodium chloride) and that’s how we can keep track of it.

Someone else asked whether anti-caking agents in salt (many different ones are used) might not be responsible for its effects on blood pressure. The answer is, it’s the salt! We regulate the sodium concentration in our bloodstream with exquisite precision. When it’s too concentrated, we’re thirsty, we add fluids to dilute the concentration, the excess fluid raises our blood pressure temporarily, but we eliminate the excess fluid over time. After a day or so, we’ve made enough visits to the loo to get rid of the excess volume, and our BP returns to normal. But if we keep bingeing on salty snacks, some of us reset out internal blood pressure detectors to a “new normal,” and develop high blood pressure. There’s a lot of individual variation. Some people seem to be programmed to retain salt, and they are more susceptible to that variety of hypertension.

The Ministry of Truth Redefines Cancer[19]!

A working group under the aegis of the National Cancer Institute (NCI) has issued recommendations that the words “cancer” and “carcinoma” be eliminated from some lesions that they consider unlikely to progress to cancer, and therefore probably do not require treatment. The motivation for making these changes is to reduce overdiagnosis and overtreatment, which they say is in many cases not only unnecessary, but harmful. These recommendations were published in the Journal of the American Medical Association (JAMA) on 29 July, and immediately widely reported.

An example of the lesions they are proposing to rename is ductal carcinoma in situ (DCIS). They propose to remove the scary word “carcinoma” from the name and relabel it as an “indolent lesion of epithelial origin,” using the accronym IDLE. Other conditions currently labelled as cancers that they are proposing to rename include prostate[20] cancer and Barrett’s esophagus. They acknowledge that in some cases, these lesions will progress to cancers, but not necessarily so in every case, and in the meantime it’s best to avoid frightening patients into demanding treatment, which might be unnecessary.

However, a paper currently in press in Molecular Oncology by Catherine Cowell and seven other investigators at Memorial Sloan Kettering puts the risk that DCIS will become metastatic breast cancer at about 40% if left untreated. The authors acknowledge that there is no current way of assessing which DCIS lesions will progress to metastatic breast cancer. The same thing is true for a number of the other so-called “IDLE” lesions that these NCI folks don’t want to scare patients about. Clearly, research is needed to identify the markers that predict which cancers will progress and which will not. But lulling patients into complacency so that they will not seek treatment strikes me as irresponsible and demeaning to patients. To the NCI and the collaborators in this exercise in semantic management of disease, I cry “Shame!”

* * * * * * *

Doc Gumshoe is having a good time writing these. He likes to exercise his little grey cells and he enjoys swimming against the tide, when the occasion seems to warrant it. He pays attention to readers’ questions and, when he doesn’t have an immediate response, he tries to heed the advice of Miss Truesdell, his 11th grade math teacher, whose usual response to “I don’t get it” was “Apply yourself!” He’ll keep applying himself! Best to all, Michael Jorrin (aka Doc Gumshoe)

Endnotes:
  1. Resveratrol: https://www.stockgumshoe.com/tag/resveratrol/
  2. cholesterol: https://www.stockgumshoe.com/tag/cholesterol/
  3. eggs: https://www.stockgumshoe.com/tag/eggs/
  4. diet: https://www.stockgumshoe.com/tag/diet/
  5. gold: https://www.stockgumshoe.com/tag/gold/
  6. inflammation: https://www.stockgumshoe.com/tag/inflammation/
  7. blood pressure: https://www.stockgumshoe.com/tag/blood-pressure/
  8. cardiovascular disease: https://www.stockgumshoe.com/tag/cardiovascular-disease/
  9. ethanol: https://www.stockgumshoe.com/tag/ethanol/
  10. AstraZeneca (AZN): https://www.stockgumshoe.com/tag/azn/
  11. Sanofi (SNY): https://www.stockgumshoe.com/tag/sny/
  12. Merck (MRK): https://www.stockgumshoe.com/tag/mrk/
  13. Novartis (NVS): https://www.stockgumshoe.com/tag/nvs/
  14. Boehringer Ingelheim: https://www.stockgumshoe.com/tag/boehringer-ingelheim/
  15. lung cancer: https://www.stockgumshoe.com/tag/lung-cancer/
  16. FDA: https://www.stockgumshoe.com/tag/fda/
  17. hypertension: https://www.stockgumshoe.com/tag/hypertension/
  18. sodium: https://www.stockgumshoe.com/tag/sodium/
  19. Cancer: https://www.stockgumshoe.com/tag/cancer/
  20. prostate: https://www.stockgumshoe.com/tag/prostate/

Source URL: https://www.stockgumshoe.com/2013/08/the-resveratrol-bust-the-arb-scare-and-other-short-takes/


54 responses to “written by reader The Resveratrol Bust, the ARB Scare, and Other Short Takes”

  1. Bob Desrochers says:

    I’m just wondering what ddugger’s educational background is, which allows him to so eloquently debunk Doc Gumshoe’s resveritrol article. Is he by chance associated with Dr Sinatra?

  2. Doug says:

    When I subscirbed I thought Stock Gumshoe was a superior financial blog. Little did I know I was signing up for Quackwatch Jr!

    Resveratrol prevents a fatal circulatory illness in rats:
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730375/
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745434/
    Does it also work in humans with the same dreadful affliction? The evidence isn’t in yet, but considering the lack of other effective treatments, I think it is worth trying.

    In general, it seems that there is a lot of good evidence that resveratrol may be a very beneficial substance, although there is still genuine doubt about whether human clinical studies will match the spectacular results in lab animals.
    http://www.ncbi.nlm.nih.gov/pubmed/23707558
    http://journals.lww.com/jhypertension/Fulltext/2010/06001/Resveratrol_Reduces_Blood_Pressure,_Changes_of.1452.aspx
    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0026391
    http://www.lef.org/magazine/mag2012/mar2012_How-Resveratrol-Combats-Leading-Causes-Death_01.htm
    http://resveratrolcentral.com/ebook/The-Case-For-Resveratrol-by-Bill-Sardi.pdf

    We still have a lot to learn about resveratrol, but I’d be quite surprised if the final answer is that it is not at all useful for assisting human health.

  3. I do think of this search for specificity as particularly American — it’s not just that we find a bit of wine to be good for you and too much to be bad and socially embarrassing, it’s that we must know exactly how much is good and what the specific line on the bottle should be at the end of the evening… and better yet, we’d rather know exactly which compound in the wine it is that’s healthful, and how much of it, and how can we get that exact amount most efficiently.

    Not that this search for knowledge is a bad trait, of course — though sometimes it obscures the more important truths of life. Sort of like the person who asks which stock will let him retire most quickly when the most appropriately holistic answer is probably, “save more, spend less”. I share that affliction, of course, in my search for specific winning ideas, sometimes the small details are more fun than the big truths.

    And just to put a cap on that, I’m cracking open a beer. And if I’m disciplined enough, I just may be able to commit to my allotted second drink as well. Damn the resveratrol, full grain ahead!

  4. packrateric says:

    One more comment on the J curve for benefit versus harm…that pont is at one drink not two in the summation of studies . As Per Uptodate: “A meta-analysis of the association between alcohol and nonfatal myocardial infarction found no additional benefit above 0.5 portion daily [17].
    A meta-analysis of data from 29 cohort studies found that the lowest mortality was associated with consumption of 5 to 7 grams of alcohol per day (about one drink every other day) [18].
    A more recent meta-analysis of 34 studies, using the same methodology as the analysis above [18] but including 10 subsequently published studies, again found that mortality was lowest at an intake of approximately 6 grams per day [19]. Although the benefit was equally strong among men and women, the dose associated with lowest mortality was lower in women than men (4 gm/day and 6 to 7 gm/day respectively). Women who drank up to two glasses of alcoholic beverage daily, and men who drank up to four glasses, had lower mortality than people who had never consumed alcohol. Twenty-six of the studies were from populations outside the US and, as noted below, the effects of alcohol vary in different geographical locations.
    In the largest study of alcohol and mortality, the maximal benefit occurred at a consumption of one drink daily for both men and women [10].
    A study of 86,000 nurses found mortality to be lowest among those women consuming one to three drinks per week (RR = 0.83 compared with abstainers), slightly lower than the mortality for women consuming up to two drinks daily (RR = 0.88 compared with abstainers) [20]. This apparent survival benefit was largely confined to women at greatest risk for coronary heart disease.

    Established recommendations for safe levels of drinking differ between men and women [16

  5. Mike Bernier says:

    Shoddy research, on your part and the rat analysis as well. You could not be more wrong. Good Luck.

  6. Jack Croes says:

    How many angels can dance on the head of a pin? The doctors and your critics who have commented on your medical article seem to be dancing around the truth. Very small differences mean too much to them. I think your article was instructive and interesting. Here and there you might have been a teensy wrong but you were slso right on many. If you come across any other medical news you want to express, I will be right here to read it.

  7. John Harris says:

    Renaming prostate cancer is hardly something to cry shame over. From what I read most of the cases labeled as prostate cancer will grow so slowly that something else will kill that man long before the prostate cancer does. Indeed most men who die of other causes late in life, who for whatever reason get autopsies, are found to have prostate cancer that was never diagnosed and did not kill them. That is the slow variety that should indeed be renamed. It is benign but still gets called cancer and subsequent rush to treatment causes untold unnecessary treatments and suffering, often with incontinence and impotence – very ugly indeed (deliver me). There is fast growing prostate cancer however that needs to be identified and treated but it is far less common. Figuring out which requires watchful waiting and during that time the patient should not be told they have cancer but have up to then at least benign lessions or some such name that does not covey the urgency for treatment.

  8. Roger says:

    I remember a discussion regarding prostate inspections, and the equally uncomfortable acts directed at women, cervical if I remember. The proposal was that these invasions mainly result in needless further medical procedures and charges, and have the unwanted consequence of driving many people away from medical exams of any kind, resulting in death from some other agent. As usual, Europe does things differently and the effect is beneficial.

  9. Mike L says:

    I agree, Resveratrol is not necessarily the magic ingredient in wine.
    Small amounts of ethanol may be. You probably don’t even have to drink the wine, just gargle with it. (Or brush your teeth once in a awhile. That’s even cheaper! )

    Untreated gum disease has been known since the 1700’s to promote death from cardiovascular disease. Infections (the chronic inflammation) might be controlled with the ethanol you get with wine (the same antibacterial in Lysterine)

    This may explain why even moderate (daily) wine drinking confers the benefit.

  10. Frank says:

    As a non-scientific person with limited medical education, I really do appreciate the comments after the Doc Gumshoe articles, both for and against, appea. And thanks to Robert Holland for his comments. What I don’t appreciate though, is the ad hominem content combined with personal attacks. They seem to come from readers, considering the vocabulary and facts and citations used, who are highly educated and knowledgeable, and have no need for it. Ad hominem comments always seem to come from those who are assuaging feelings of inner anger and personal deficiencies, and are usually aimed at covering up lack of intelligent argument with insults. This lack of reasonable, rational argument doesn’t seem to be the case her. Why the insults? It’s just the man’s opinion !

  11. packrateric says:

    A 41 percent increase in the risk of breast cancer
    Occurs in women who consume 2 to 5 drinks per day .

    This is not a “very small difference ” nor” is it dancing around the truth”

    It is fair warning that 2 drinks per day is not safe or healthy for half the population ( women). Reference is Uptodate.

    At these levels of risk if alcohol were to be judged by the FDA drug standards it would not have a prayer.

  12. Ethan says:

    Thanks Doc Gumshoe for exercising your grey blob.

    The piece about over-diagnosing and over treatment was the most interesting to me.

    Ethan

  13. Abelhorn says:

    I would suggest you do an updated study on Resveratrol, as there is much new information from many sources, in other words before you rant please know
    what your talking about, (Wikipedia then to the companies) are you kidding me?

  14. Nuttsman, PhD says:

    The real paradox in the French Paradox is that only red wine confers the benefit. So, although it is probably not resveratrol that confers the benefit it stands to reason that in fact the colored compounds found in red wine have a protective effect on the heart and arteries. Hence, your statement: “So it’s not the red stuff in the wine, it’s the ethanol that confers those benefits. ” is probably false. White wine has just as much alcohol as red wine, yet confers no specific protection. Studies point to the antioxidant potency of the anthocyanins and procyanins (both colored compounds) as the possible protective molecules in red wine. These are also found in other fruits and juices that contain no alcohol. Alcohol may be beneficial in small amounts but the potencial for harm would appear to be much greater than the potential for improved health.

  15. yobee says:

    An alternative explanation of the French Paradox is that the French eat lots of Vitamin K2 rich foods that we have been told for half a century to avoid, such as egg yolks, cream, cheeses and lamb and other fatty meats. Vitamin K2 activates two proteins, one of which removes calcium from arteries and other soft tissues, and the other which deposits the calcium in bone, where it should be. See “Vitamin K2 and the Calcium Paradox” by Kate Rheaume-Bleue for an interesting review of this fairly new science. Personally, K2 supplements reversed my angina in about three weeks.

  16. Gerald says:

    It’s “educational” to see that 95% approx of all comments are about booze…. My comment will likely be lost in the shuffle, but I couldn’t find a “reply” on top of the Gumshoe newsletter, which might have had a chance of being read.
    Simply the ridicule of the doctor who pointed out that there was about a 24% increased risk with using ARB was very unmerited. the figures in the study showed that the incidence increased from .7% to .9%. That is simply an increase of .2% on a figure of .7% which to me is a more than 25% increase, likely about 27%.

    And the same thing with the increase with the HRT (Hormone replacement) from 30 per 10,000 to 37 per 10,000.
    That’s an increase of 7 on 30 which is a little less than 25%, so the much laughed at 23% seems accurate.
    The dissident doctors are not disputing that the increase is small in actual numbers, taking into consideration the large amount of participants, but what they say seems to me to be accurate..
    Just a matter of pointing out what I see. And, of course I could always be wrong……

  17. Jennifer Estes says:

    It seems you have hit a nerve but I applaud you effort to keep us thinking and reading. . Years ago I asked my doctor about resveratrol after seeing it on TV as the supplement to keep young. His comment was, it make not keep you young but there didn’t seem to be a down side, so I began taking it and I will continue. I would love to see what you would find in joint treatment with PRP or Prolotherapy, both which I have had for my back and knees. In both situations I avoided surgery and in the case of my back have been without pain for 13 years after just three treatments. I play tennis and golf, at age 63, and hope to continue until I am 85. Also, red rice yeast instead of statins, which finally got my cholesterol below 200, would be an interesting study. You may not be a doctor, but you bring much to us in your articles, be it finance or health. Thank you.

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