I have to apologize for being absent from your email inbox for a month. It's been for a good cause. Why? Read on.

 

My biomedical background to the rescue

Currently, I am co-principal investigator with a study on environmental chemicals which has been approved by the Committee on Human Research at the University of California San Francisco School of Medicine and supported by the Center for Research on Environmental Chemicals in Humans.

Two articles in this installment

The effort took me nearly a month because I needed to write two articles.

The first was to examine and document confirm every small scientific part of the original article.

The second is a supplementary article explaining the method0logy of the study.

My intent has been to write both articles in such a way as to be approachable to an intelligent non-scientist.

Indeed, as the author of 23 published books, I have been told by every editor and publisher I have ever worked with that each footnote in a book cuts readership by a half.

That's why this draft version is intended for a non-scientist. If merited, the main article will be condensed and footnoted for submission to The Lancet as a statement of concern.

The summary of the 4.578-word premium article is below.

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The Mendelian Randomization by Millwood et al.: Observations and Expressions of Concern

Non-scientist draft - may be edited for scientific publication.

The recent population study of adults in China that found no cardio-protective benefits of moderate alcohol consumption should be re-examined in the context of methodological and confounding factors not addressed in the published paper.

Published in early April by The Lancet, the study provoked sensational headlines among the general media proclaiming the definitive death of the "myth that moderate drinking can be healthy."

The new study -- by a unit of Oxford University -- is remarkable for its parallel use of two different methods -- conventional epidemiology and Mendelian Randomization (MR) -- to re-analyze data from a large Chinese population study conducted from 2004-2008.

The Oxford study's conventional epidemiology method found a familiar "J-shaped" curve found in some previous studies.

By contrast, the MR method found no increased risk or benefit from myocardial infarction but increased risks of stroke -- both hemorrhagic and ischemic.

Accordingly, the study concluded that, "Genetic epidemiology shows that the apparently protective effects of moderate alcohol intake against stroke are largely non-causal. "

However, a close examination of the study, its supplemental materials and other data indicate methodological concerns including:

• Flaws in the study's instrumental variable: The choice of the gene variants violate the exclusion principal -- a primary requirement for a valid MR
• An invalid comparison between the results found between men and women
• Failure to account for vast differences in tobacco smoking between men and women
• Failure to correct for self-reporting/under-reporting errors in alcohol consumption when creating genotype-calculated categories for MR statistical analysis.
• An over-stated extrapolation of results to all alcoholic beverages despite evidence that spirits was the overwhelming beverage of choice
• Failure to control for contaminants found in Asian spirits
• Defined "moderate drinking" as 100 grams of alcohol or less, yet emphasized the relative risks at an overstated median level of 280 grams per week which is substantially above moderate.

In addition, the study suffers from a widespread lack of needed citations/footnotes on a number of key assertions.

The study text fails to consistently draw a clear distinction from pre-existing Biobank methods and data and those developed and used by investigators in the present study.

The remainder of this 4,758-word article -- AND a second one on Mendelian Randomization -- are available for Wine Executive News premium subscribers. who may Log-In Here:

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Also in this article:

• Mendelian Randomization: A Statistical Tool to Estimate Causation

• The study summary

• Results from conventional epidemiology

• Results from Mendelian Randomization (MR)

• MR Population Selection

• "Flush" syndrome is most prominent in East Asians

• Alcohol metabolism and two key polymorphisms

• Randomization Through Simulation of Controlled Trials

• Methodology

• Flawed Instrumental Variable

• Acetaldehyde sources widespread in foods, beverages, tobacco and marijuana

• Flawed assumptions in de facto "control" population

• Fact check needed on alcohol consumption data

• Women, smoking and acetaldehyde: confounding factors

• Alcohol & acetaldehyde - different effects in men and women

• Results most likely not applicable beyond spirits consumption

• Formaldehyde and inherent acetaldehyde levels in Asian spirits may complicate health

• Not broadly applicable beyond East Asian genotypes

• Under-reporting could affect genotype-calculated categories

• WHO consumption at odds with Millwood.

• Recall and alcohol content issues

• Social barriers may encourage under reporting.

• Study self-selection bias

• Suggestions offered for further evaluation of instrumental variables in a manner that increases credibility

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