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From the Lancet study linked above:

 

The main finding of this analysis was that the threshold for lowest risk for all-cause mortality was about 100 g per week.

 

But the study does not say anything about how  a low alcohol  intake compares to not drinking at all.

 

To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.

 

When including never-drinkers and ex-drinkers, we reproduced previously reported U-shaped associations of alcohol consumption with total cardiovascular disease and all-cause mortality (appendix p 31).

 

We focused our study on current alcohol drinkers for three main reasons. First, alcohol guidelines provide recommendations about low-risk limits only for drinkers (we are unaware of any guidelines that encourage non-drinkers to consume alcohol).

 

That's nice, but that's precisely the issue of interest to most people here-- whether to drink a small amount of alcohol or not.   Doesn't eliminating non-drinkers practically guarantee that the previously discussed J-shaped curves would  be eliminated?

 

Second, a focus on current drinkers should limit potential biases that are difficult to control in observational studies (eg, reverse causality, residual confounding, and unmeasured effect modification) because ex-drinkers include people who might have abstained from alcohol owing to poor health itself,18,19,20 as well as those who have changed their habits to achieve a healthier lifestyle. Third, never-drinkers might differ systematically from drinkers in ways that are difficult to measure, but which might be relevant to disease causation.21

 

But more recent studies showing  J-shaped curves have in fact tried to deal with such potential biases, as discussed here (--you'll never learn about them from Dr. Greger!) :

 

https://www.crsociety.org/topic/13018-alchohol-a-potent-medicine/?do=findComment&comment=28552

 

Study co-author Doctor Sreenivas Veeranki, assistant professor in preventive medicine and community health at University of Texas Medical Branch, said: "We have taken rigorous statistical approaches to address issues reported in earlier studies such as abstainer bias, sick quitter phenomenon and limited confounding adjustment in our study. "

 

Cf. Beneficial Effects of Moderate Alcohol Use--A Case for Occam's Razor?  (2017)

https://onlinelibrary.wiley.com/doi/pdf/10.1111/add.13550
 

There are many potential biases in observational research that may render spurious the beneficial effects of moderate alcohol use. Most of them have been accounted for in more recent research, and observational findings have been supported by biological pathways. As long-term clinical trials of moderate alcohol use seem infeasible and unethical and Mendelian randomization has its own caveats, more well-designed observational studies showing no beneficial effects are needed to rule out the currently still probably beneficial effects of moderate alcohol use.

 

Naimi and colleagues [1] greatly remind us of potential biases in observational research, particularly with regard to the potentially beneficial effect of moderate alcohol consumption, for example, for coronary heart disease (CHD). One solution to curtail these biases may be seen in a long-term randomized clinical trial of moderate alcohol consumption starting at an early age, when initiation of alcohol use takes place, and to follow individuals up to death,for example for more than 60 or 70 years. Although theoretically desirable, such a trial seems practically and ethically not feasible.

 

Some of the mentioned biases such as the abstainer bias[2] or (residual) confounding have been discussed over decades and newer studies have addressed earlier criticism carefully. Already the original paper on the abstainer bias(sick quitter effect) [3] has not received unanimous consent in a complete supplement of the Annals of Epidemiology in2007 [4]. Similarly, meta-analyses taking into account numerous confounders found that the beneficial effect mightbe attenuated in better-adjusted studies, but the attenuation was small and did not rule out the beneficial effect of  moderate alcohol use [5,6]

Edited by Sibiriak

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From the Lancet study:

 

Our results are concordant with recent observational data and Mendelian randomisation studies.  16,43,44,45,46

 

#16 takes us to the "recent observational data":

 

Alcohol consumption and cardiovascular disease, cancer, injury, admission to hospital, and mortality: a prospective cohort study

 

http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(15)00235-4.pdf

 

Findings   

 

We included 114 970 adults, of whom 12 904 (11%) were from high-income countries (HICs), 24 408 (21%) were from upper-middle-income countries (UMICs), 48 845 (43%) were from lower-middle-income countries (LMICs), and 28 813 (25%) were from low-income countries (LICs). Median follow-up was 4·3 years (IQR 3·0–6·0). Current drinking was reported by 36 030 (31%) individuals, and was associated with reduced myocardial infarction (hazard ratio   0.76 [95% CI 0·63–0·93]), but increased alcohol-related cancers (HR 1·51 [1·22–1·89]) and injury (HR 1·29 [1·04–1·61]). High intake was associated with increased mortality (HR 1·31 [1·04–1·66]). Compared with never drinkers, we identified significantly reduced hazards for the composite outcome for current drinkers in HICs and UMICs (HR 0·84 [0·77–0·92]), but not in LMICs and LICs, for which we identified no reductions in this outcome (HR 1·07 [0·95–1·21]; pinteraction<0·0001).

 

Mendelian randomization has its own issues  (but of course you won't hear about them from Dr. Greger.)
 

Modelling the impact of alcohol consumption on cardiovascular disease mortality for comparative risk assessments: an overview (2016)

 

https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-016-3026-9

 

There is an ongoing debate as to whether the beneficial effects of alcohol consumption in terms of a protective effect on ischaemic diseases are real. The newest contribution to this discussion comes from Mendelian randomization studies [63, 64], where Holmes and colleagues [63] recently investigated the role of alleles of the ADH1B gene on IHD risk. The rs1229984 A-allele has been found to lead to an increased metabolization of alcohol into acetaldehyde [65] (acetaldehyde is associated with negative effects, including a flushing response). Holmes and colleagues showed that carrying the rs1229984 A-allele was associated with less consumption in terms of both average alcohol consumption and binge drinking, and with a lower IHD risk.

 

While Holmes and colleagues concluded that there is no beneficial effect of alcohol consumption on IHD risk, their findings do not rule out a beneficial effect of low average alcohol consumption without binge drinking. However, the findings highlight the need for careful interpretation of the evidence. Meta-analyses of high quality observational studies, supported by short-term experimental studies on biomarkers for IHD risk, identified a curvilinear relationship between average alcohol consumption and IHD risk, and a modifying effect from episodic heavy drinking (see also [66]). We would expect on average low or moderate alcohol consumption coupled with no binge drinking to show less IHD risk compared to other drinkers. If this rather complex relationship is not reflected in the analysis, interpretation becomes increasingly difficult. Moreover, certain assumptions must be met in order to assess the validity of the findings from a Mendelian randomization analysis, and the conclusions of such an analysis depend on these assumptions.

 

First, it was assumed that all of the effect of the allele was mediated through alcohol consumption. However, only a small percentage of the variation of alcohol consumption is explained by ADH1B genotypes, or by other genes related to alcohol consumption, such as ALDH2. Furthermore, it is assumed that the risk for IHD is identical for carriers and non-carriers, except for the effect of the allele. Additionally, the effect of the allele, other than a reduction in alcohol exposure, must be independent from IHD risk. However, Holmes and colleagues demonstrated that the rs1229984 A-allele was associated with several IHD risk factors. Another problem lies in the statistical power required to examine such a complex association. Only a small percentage of the population studied by Holmes and colleagues carried the rs1229984 A-allele and, thus, investigations in populations where carriers are more common might remedy this problem.

 

While Mendelian randomization has theoretical advantages over observational studies, it is unknown whether such an investigation of the ADH1B gene meets the assumptions necessary to yield unbiased results, particularly in more complex analyses. More research on the influence of several different genes on alcohol consumption and their influence on IHD risk is necessary to validate and correctly interpret the findings from this and other Mendelian randomization studies.

 

 

Beneficial Effects of Moderate Alcohol Use--A Case for Occam's Razor?  (2017)

 

Naimi et al . [1] provide ideas for improvement of observational research designs; however, I would not place too much expectation upon Mendelian randomization studies. Certainly, this method is appealing and may reduce confounding, but also has a number of caveats in addition to confounding by population structure, pleiotropy or linkage disequilibrium [15].

 

More specifically, the study of Holmes et al.[16] has received a number of critical comments, e.g. that the allele should predict cardiovascular disease risk only via alcohol use, an assumption of Mendelian randomization that was apparently violated [17,18]. Mendelian randomization is basically an instrumental variable  approach, in which the instrument is used as a kind of proxy measure for the exposure. The method depends upon the use of strong instruments, i.e. instruments that are correlated highly with the exposure (the exposure is predicted from the instrument and then used in the original model), but uncorrelated with the disturbance terms. Holmes et al. [16] used variants involved in alcohol dehydrogenase 1B (ADH1B), but genetic variants involved in aldehyde dehydrogenase 2 (ALDH2) are seen commonly to haves substantially more influence on alcohol intake. However, even using ALDH2, as in the study by Au Yeung et al. [19] on cognitive functioning, explained only 3% of the variance of alcohol use. The use of weak instruments leads to large standard errors and often to even more biased results than the use of the exposure variable itself [20,21].

 

Mendelian randomization may be useful for increasing risk associations monotonically or testing potential biological mechanisms underlying the alcohol–disease association; however, it seems unlikely that alleles of a single-nucleotide polymorphism with basically three categories (e.g. AA, GA, GG of ALDH2; sometimes even two were combined due to low case numbers) may be sufficient to predict curvilinear relationships or to approximate the complex interplay between volume drinking and binge drinking [22].

 

In the sense of Occam’s razor: if you have two theories that both explain the observed facts, then you should use the simplest until more evidence comes along. Given all the complex explanations against a beneficial effect, I would still go with the simpler explanation of a true beneficial effect. Naimi et al [1], however, provided highly valuable insight into how more evidence may come along.

Edited by Sibiriak

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It seems that the Lancet study (Woods et al., 2018) confirms what we have been discussing so far. 

 

  • CVD hazard: there is an optimum, located at about 100 g/week, which exhibist the lowest mortality hazard for CVD
  • All-cause mortality: there is a threshold, located at about 100 g/week, above which mortality increases and below which mortality remains constant. In the lower dose region, evidently pros and cons balance almost perfectly, with a net nihil effect.

So one sensible strategy, already discussed, would be that those who are at greater risk of CVD would benefit most of drinking about 100 g/week alcohol, which is 14 g/d which corresponds to exactly one drink, or about 18 mL/day, which is 123 mL of a stron 14.5% red wine. 

 

If not at risk for CVD, we should not drink at all or, if we wish to drink, we should drink less than a drink per day.

 

The above strategy neglects totally the potential benefits of phenolic compounds present especially in red wines. If Acutissimin-A in oak-aged red wines is really present in doses sufficient to prevent cancer, then drinking such wines would offset the putative carcinogenic effect of alcohol.

 

gr1_lrg.jpg

Edited by mccoy

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A new study, published yesterday: Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Quote

 

Summary

Background

Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.

Methods

Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.

Findings

Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2·2% (95% uncertainty interval [UI] 1·5–3·0) of age-standardised female deaths and 6·8% (5·8–8·0) of age-standardised male deaths. Among the population aged 15–49 years, alcohol use was the leading risk factor globally in 2016, with 3·8% (95% UI 3·2–4·3) of female deaths and 12·2% (10·8–13·6) of male deaths attributable to alcohol use. For the population aged 15–49 years, female attributable DALYs were 2·3% (95% UI 2·0–2·6) and male attributable DALYs were 8·9% (7·8–9·9). The three leading causes of attributable deaths in this age group were tuberculosis (1·4% [95% UI 1·0–1·7] of total deaths), road injuries (1·2% [0·7–1·9]), and self-harm (1·1% [0·6–1·5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27·1% (95% UI 21·2–33·3) of total alcohol-attributable female deaths and 18·9% (15·3–22·6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0–0·8) standard drinks per week.

Interpretation

Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.

Funding

Bill & Melinda Gates Foundation.

 

Here is a report on the study in the Guardian: No healthy level of alcohol consumption, says major study

Quote

Most national guidelines suggest there are health benefits to one or two glasses of wine or beer a day, they say. “Our results show that the safest level of drinking is none.”... Moderate drinking has been condoned for years on the assumption that there are some health benefits. A glass of red wine a day has long been said to be good for the heart. But although the researchers did find low levels of drinking offered some protection from heart disease, and possibly from diabetes and stroke, the benefits were far outweighed by alcohol’s harmful effects, they said.

I find these studies highly persuasive.

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28 minutes ago, Thomas G said:

I find these studies highly persuasive.

Yes, but pure alcohol is most probably different from alcohol and  red, hi-polyphenols wine with its TP, including stilbenes and the rare Acutissimin A if aged in oak. These are xenohormetic compounds which may reverse the hazard profile. We should need a very specific study here.

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38 minutes ago, Sibiriak said:

Confirmation bias.

When I first started practicing CR seriously, I was drinking 6 oz of red wine a day. I didn't do that every day, or even most days, but I did it on a semi-regular basis.

I changed my mind as a result of studies like these. I have no ideological stakes against alcohol and I am willing to change my mind again, but the recent studies seem pretty solid to me and I'm going with them for the time being.

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8 minutes ago, Sibiriak said:

Thomas G,  what do you mean "studies like these"?

Studies like the one I linked to above: Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

As well as this one by Jennie Connor: Alcohol consumption as a cause of cancer

And this one: No Benefit of Light to Moderate Drinking for Mortality From Coronary Heart Disease When Better Comparison Groups and Controls Included: A Commentary on Zhao et al. (2017)

My current position is that whatever minor health benefits for cardiovascular disease are gained by drinking moderate amounts of red wine are outweighed by the increased risk of cancer. I see no reason to prefer drinking a glass of wine over eating a handful of grapes.

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Hi Thomas!

When you eat your handful of grapes, you're consuming a lot of sugar.  It's unclear which is worse:  the sugar in the handful of grapes, or the alcohol that can be obtained by fermenting them.

  ?

  --  Saul

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@ Thomas G   The fermentation process (not to mention oak barrel aging etc. which Mccoy has discussed) radically alters the phytochemical profile of grape wine compared to raw grapes  (which is not to say that eating grapes in moderation is necessarily bad).   Michael Rae stressed this fact when discussing a possible red wine extract supplement:

Quote

Michael Rae: ....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.   https://www.crsociety.org/topic/11395-prostate-cancer-prevention/?page=2


( Dealcoholized red wine is another topic briefly discussed in that thread.)

 

Edited by Sibiriak

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Two points, one wine when it is studied alone shows lower rates of cancer and CAD overall. Lower rates of CAD even at relatively high amounts >3 drinks daily. So wine is a separate entity and should be excluded from conclusion based on “alcohol” studies.

 

two: I would also love to know how the come to conclusions like 100 grams of alcohol a week? In my area for example lots of people I know are into margaritas at tres amigos a restaurant chain. Try one of them sometimes. It’s not one drink they way these studies define a drink. I know lots of people who drink. Bright and intelligent people and 5oz. Of wine is not a “drink” for most of them. Beer is easier to track, but liquor is notoriously easy, very easy to “cheat” because many just dump some into the mix and don’t measure it and when they do this you can almost bet that the drink will not be what the researchers classify as such.

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This abstract was posted by alpater, apparently contradicting the fact that alcohol tends to increase cancer risk. A contradictory topic indeed.

 

Alcohol Intake and Risk of Lethal Prostate Cancer in the Health Professionals Follow-Up Study.
Downer MK, Kenfield SA, Stampfer MJ, Wilson KM, Dickerman BA, Giovannucci EL, Rimm EB, Wang M, Mucci LA, Willett WC, Chan JM, Van Blarigan EL.
J Clin Oncol. 2019 Apr 26:JCO1802462. doi: 10.1200/JCO.18.02462. [Epub ahead of print]
PMID: 31026211
Abstract
PURPOSE:
It is unknown whether alcohol intake is associated with the risk of lethal (metastatic or fatal) prostate cancer. We examine (1) whether alcohol intake among men at risk of prostate cancer is associated with diagnosis of lethal prostate cancer and (2) whether intake among men with nonmetastatic prostate cancer is associated with metastasis or death.
METHODS:
This prospective cohort study uses the Health Professionals Follow-Up Study (1986 to 2012). Our analysis of alcohol intake among men at risk of prostate cancer included 47,568 cancer-free men. Our analysis of alcohol intake among men with prostate cancer was restricted to 5,182 men diagnosed with nonmetastatic prostate cancer during follow-up. We examine the association of total alcohol, red and white wine, beer, and liquor with lethal prostate cancer and death. Multivariate Cox proportional hazards regression estimated hazard ratios (HRs) and 95% CIs.
RESULTS:
Alcohol drinkers had a lower risk of lethal prostate cancer (any v none: HR, 0.84 [95% CI, 0.71 to 0.99]) without a dose-response relationship. Total alcohol intake among patients with prostate cancer was not associated with progression to lethal prostate cancer (any v none: HR, 0.99 [95% CI, 0.57 to 1.72]), whereas moderate red wine intake was associated with a lower risk (any v none: HR, 0.50 [95% CI, 0.29 to 0.86]; P trend = .05). Compared with none, 15 to 30 g/d of total alcohol after prostate cancer diagnosis was associated with a lower risk of death (HR, 0.71 [95% CI, 0.50 to 1.00]), as was red wine (any v none: HR, 0.74 [95% CI, 0.57 to 0.97]; P trend = .007).
CONCLUSION:
Cancer-free men who consumed alcohol had a slightly lower risk of lethal prostate cancer compared with abstainers. Among men with prostate cancer, red wine was associated with a lower risk of progression to lethal disease. These observed associations merit additional study but provide assurance that moderate alcohol consumption is safe for patients with prostate cancer.

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