220 Commentaries
SELECTION BIAS AND RELATIONSHIPS
BETWEEN ALCOHOL CONSUMPTION AND
MORTALITY
It is precisely because of the conflicted science and
methodological limitations, including selection bias, that we
should apply the Precautionary Principle to the matter at
hand, rather than Occam’s razor. This requires that the
burden of proof rests on demonstrating clear benefit with
high-level evidence before recommending alcohol as a
preventative agent.
We appreciate the insightful comments from the eminent
Drs Britton & Bell, Gmel and Roerecke. While we agree
with Britton & Bell’s [1] assertion that modeling potential
benefits from low-volume consumption has little impact
on reducing world-wide estimates of harms, scientific con-
clusions about health effects of ‘moderate’ alcohol con-
sumption shape general attitudes about alcohol
consumption. In particular, concepts of health benefit are
used to oppose alcohol control policies, factor into develop-
ment of public health guidelines and complicate public
health and clinical messaging.
Our concerns with selection bias [2] were made
with regard to limitations about observational evidence,
and life-course analysis (such as that by Britton & Bell)
can greatly reduce selection bias. We agree that selec-
tion bias applies to both drinkers and non-drinkers,
but overall favors positive findings for drinkers. This is
because many former drinkers (who, typically, are re-
moved from drinker–non-drinker comparisons) may quit
for reasons of ill health, including that related to alco-
hol consumption itself. Conversely, life-time abstainers
appear to have poorer health and social profiles, even
at young ages [3]. Finally, in all-cause mortality studies,
death preceding cohort inception—particularly among
younger people—is due more probably to alcohol con-
sumption among drinkers than to a lack of consump-
tion among non-drinkers. Randomized trials can
address some aspects of selection bias that are difficult
to overcome with life-course analysis (e.g. performing
true intention-to-treat analyses), and are the best way
to mitigate confounding.
Gmel’s well-argued case for applying Occam’s razor to
simplify the argument and accept the J-curve as evidence
of ‘a true beneficial effect’ [4] is growing more difficult
to defend. For starters, a J-curve suggesting initial mortal-
ity benefit that inflects positively above low levels of con-
sumption does not beg a simple explanation, and can be
an epidemiological red flag for spurious associations.
Beyond the recent meta-analysis finding of no protection
for all-cause mortality among low-volume drinkers after
adjusting for study quality and abstainer biases [5],
© 2017 Society for the Study of Addiction
and the Mendelian randomization study finding no pro-
tection against coronary heart disease (CHD) events
[6], arguments for biological plausibility have weakened.
High-density lipoprotein cholesterol (HDL-c), which is
raised by alcohol consumption in experimental studies,
has been discredited as a causal factor for CHD on the
basis of a Mendelian randomization study [7] a meta-
analysis of statin trials that adjusted for their low-density
lipoprotein (LDL) effects [8] and multiple failed drug trials
of HDL-raising pharmacological agents [9]. In observa-
tional and Mendelian randomization studies increased
alcohol consumption is associated with higher blood
pressure and hypertension, and in observational studies
increased alcohol consumption is associated with
increased carotid intima media thickness and coronary
calcification [10]. In a meta-analysis of experimental
studies, low-volume alcohol consumption does not lower
blood glucose among diabetics [11], and two randomized
studies that found benefit from the Mediterranean diet for
CHD outcomes were not randomized with respect to alco-
hol [12,13], suggesting that diet is the driver behind the
‘French paradox’.
It is precisely because of the conflicted science and
methodological limitations, including selection bias, that
we should apply the Precautionary Principle, rather
than Occam’s razor, to the matter at hand. This re-
quires that the burden of proof rests on demonstrating
benefit with high-level evidence before recommending
alcohol as a preventative agent. Indeed, we echo
Roerecke’s [14] note of caution, particularly with re-
spect to policy development and drinking guidelines.
Compared with benefits, the addictive and adverse
health effects are not only larger but are more scientif-
ically compelling, to the extent that they are led by
conditions that are wholly alcohol-attributable or that
have high relative risk estimates, conditions for which
alcohol is one of a relatively small number of risk
factors, and/or conditions where the latency between
exposure and outcome is short. Observed relationships
between low-volume alcohol consumption and CHD
lack these attributes. While we agree with Roerecke
that it is important to assess cause-specific outcomes,
when it comes to a substance associated with multiple
outcomes across the life-course, all-cause mortality
seems the most important outcome to gauge
accurately.
Declaration of interests
None.
Keywords Alcohol, drinking, moderate drinking,
mortality, precautionary principle, selection bias.
Addiction, 112, 215–221

TIMOTHY S. NAIMI1, TIMOTHY STOCKWELL2,
RICHARD SAITZ3 & TANYA CHIKRITZHS4
Section of General Internal Medicine, Boston Medical Center, Boston,
Massachusetts, USA1 Centre for Addiction Research of BC, University
of Victoria, Victoria, British Columbia, Canada2 Department of
Community Health Sciences, Boston University School of Public
Health, Boston, Massachusetts, USA3 and National Drug Research
Institute, Curtin University, Perth, Australia4
E-mail: tim.naimi@bmc.org
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Commentaries 221
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