JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
8, 2017
ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER
EDITORIAL COMMENT
Alcohol and Health
Praise of the J Curves*
Giovanni de Gaetano, MD, PHD, Simona Costanzo, MS, PHD
T he accepted interpretation of the J-shaped
curve relating alcohol intake to cardiovascu-
lar events or mortality is that the lowest point
on the curve (light-to-moderate drinking) represents
optimum exposure to alcohol, and the increased risk
in nondrinkers or heavy drinkers reflects the conse-
quence of suboptimal exposure. This means that un-
like tobacco, for which there is no safe level of
consumption (Figure 1), the nadir of J-shaped curves
for alcohol (Figure 2) is proposed as a healthy range
for the general population (1,2).
Numerous studies have used J-shaped curves to
describe the relationship between alcohol use and
total mortality. In a meta-analysis of 34 prospective
studies in men and women, including more than 1
million subjects and more than 94,500 deaths (2), a
clear J-shaped relationship between alcohol intake
and mortality was observed. After an initial reduction
in mortality, as alcohol intake increased, the curve
reached a nadir and then showed an increase in
mortality at higher doses (Figure 2). The lowest mor-
tality risk (
19%) was observed at 6 g/day of
alcohol or approximately one-half of a drink per
day, but lower mortality compared with no alcohol
consumption was observed with up to 4 drinks/day in
*Editorials published in the Journal of the American College of Cardiology
reflect the views of the authors and do not necessarily represent the
views of JACC or the American College of Cardiology.
From the Department of Epidemiology and Prevention, IRCCS Istituto
Neurologico Mediterraneo NEUROMED, Pozzilli, Italy. Dr. Costanzo is a
visiting scientist at the Department of Nutrition, Harvard TH Chan School
of Public Health, Boston, Massachusetts, as the recipient of a Fondazione
Umberto Veronesi Travel Grant. Dr. de Gaetano is a member of the
International Scientific Forum on Alcohol Research, an independent
organization of scientists that prepares critiques of emerging research
reports on alcohol and health. The members of the Forum donate their
time and effort in the review of papers, and receive no financial support.
The Forum itself receives no support from any organization or company
in the alcoholic beverage industry. He is also a consultant to the Web
Newsletter of Assobirra, the Italian Association of the Beer and Malt
Industries; and is a corresponding member of the nonprofit Accademia
Italiana della Vite e del Vino. Dr. Costanzo has reported that she has no
relationships relevant to the contents of this paper to disclose.
VOL. 70, NO.
ISSN 0735-1097/$36.00
http://dx.doi.org/10.1016/j.jacc.2017.07.710
men and 2 drinks/day in women. Higher doses of
alcohol were associated with increased mortality (2).
The basic J-shaped curve persisted after adjustment
for many relevant confounding variables.
However, prominence is often given to the hy-
pothesis that the well documented J-curve relation-
ship of lower risk of mortality with light-to-moderate
alcohol intake might be due to a misclassification of
drinking patterns. The higher risk among abstainers
might have been due to the inclusion of high-risk
subjects who had become abstainers (3).
In 2010, an analysis of 9 nationally representative
samples of U.S. adults showed that light-to-moderate
alcohol consumption was inversely associated with
cardiovascular mortality (4).
Compared with lifetime abstainers, a significant
protection of 31% and 38% among light and moderate
drinkers was found, respectively. The magnitude of
lower risk was similar in subgroups of sex, age, or
baseline health status. There was no simple relation
of drinking pattern with risk, but risk was consis-
tently higher among those who consumed >3
compared with 2 drinks/day (4).
SEE PAGE 913
In this issue of the Journal, Xi et al. (5) analyzed the
amount of alcohol intake and risk of all-cause, cardio-
vascular, and cancer deaths in 333,247 American adults
from 13 waves of U.S. National Health Interview
data. After a median follow-up of 8.2 years, 34,754
participants died from all causes (including 8,947
cardiovascular disease [CVD] deaths and 8,427 cancer
deaths). Compared with lifetime abstainers, light-to-
moderate alcohol consumers were at significantly
reduced risk of all-cause (light:
21%; moderate:
22%)
and CVD mortality (light:
26%; moderate:
29%),
respectively. In contrast, significantly increased risks of
all-cause (11%) and cancer mortality (27%) were found
in adults with heavy alcohol consumption compared
with those who never consumed. The data by Xi et al. (5)
924 de Gaetano and Costanzo JACC VOL. 70, NO. 8, 2017

Alcohol and Health AUGUST 22, 2017:923–5

the alcohol–mortality association” may look like a

F I G U R E 1 All-Cause Mortality Risk: Smoking
religious claim. However, it was not a theological
statement, but a robust scientific conclusion. Their
1.9 Pnon-linearity = 0.12
work helps clarify the debate over the existence of a
J-shaped curve, an issue frequently discussed as a
problem of beliefs rather than scientific data.
1.5
The number of people involved in their study was
Hazard Ratio

impressive, the methodology sound (inclusion of only

1.2
1 tant ancillary analyses. The results supported the
0 5 10 15 20 25
Smoking Intensity (Cigarettes/Day)
Fitted linear trend
Dose-response analyses of smoking intensity show a linear risk of all-cause mortality.
CI ¼ confidence interval. Reprinted with permission from Wang et al. (1).
appear to be largely confirmatory (2,4,6), but the au-
thors have pointed out relevant drawbacks from some
of the previous studies, such as “abstainer bias” or
inappropriate adjustment for confounders or different
patterns of alcohol drinking.
The conclusion by Xi et al. (5) that their study
“re-emphasized the existence of a J-shaped curve in
F I G U R E 2 All-Cause Mortality Risk: Alcohol
1.4
1.3
Relative Risk of Total Mortality
lifetime abstainers in the reference group), and the
statistical approach correct and supported by impor-
conclusion that the J-shaped relationship between
alcohol consumption and mortality risk cannot be
dismissed and should guide the formulation of public
policies on alcohol consumption.
30 35 40 Alcohol’s multiple effects on health not only
depend on quantities but also on patterns of alcohol
95% CI use (whether intake is concentrated—such as during
weekends—or regularly dispersed during meals) (7).
Binge drinking was also associated with a significant
increased risk of all-cause (13%) and cancer mortality
(22%) (5). Consistent with some previous observa-
tions, they also failed to show heavy or binge drinking
to be associated with CVD-specific mortality. In a very
recent study, heavy drinkers were more likely to
initially present with death from causes other than
CVD (8); this might be due to competing risks in
heavy or binge drinkers, or it might mean that they
are less likely to initially present with any CVD
because they die from other causes before developing
CVD. Another explanation might be that even
ingesting large amounts of polyphenols from heavy
alcohol consumption might have some protective ef-
fect on the cardiovascular system (9).

Numerous mechanisms have been proposed to

1.2
explain the benefit that light-to-moderate alcohol
1.1 intake has on the heart, including an increase in high-
density lipoprotein cholesterol and fibrinolysis;
1.0
reductions in plasma viscosity, fibrinogen concen-
0.9 tration, and platelet aggregation; improvement in

0.8
endothelial function; reduction in inflammatory re-
sponses; and promotion of antioxidant effects. Con-
0.7 troversy exists about whether alcohol has a direct
0.6 cardioprotective effect on the ischemic myocardium
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 (2,10). Conversely, alcoholic cardiomyopathy, a rare
g/d consequence of severe alcohol use disorders, is
thought to be a direct consequence of alcoholic
0 1 2 3 4 5 6 7
cytotoxicity (10).
Drinks Per Day
Alcohol Consumption Another important result presented by Xi et al. (5):
light alcohol consumption appeared to be protective
Fixed Model (n = 56) Random Model (n = 56)
against cancer mortality. Although there is general
agreement that heavy alcohol is associated with
Dose-response analyses of alcohol consumption show J-shaped curves to the risk of
all-cause mortality. Reprinted with permission from Di Castelnuovo et al. (2).
increased cancer risk (10,11), some public organiza-
tions insist on considering alcohol harmful even when
JACC VOL. 70, NO. 8, 2017 de Gaetano and Costanzo 925
AUGUST 22, 2017:923–5 Alcohol and Health

consumed in light amounts (“zero tolerance”) (12). In
line with Xi et al. (5), a recent meta-analysis of
60 cohort studies concluded that light drinking was
not associated with the incidence of most cancers
except for a mild increase of female breast and male
colorectal cancer, although it was not associated with
increased breast cancer mortality (13). The important
issue of possible cancer risk from light-to-moderate
alcohol intake remains clouded by uncertainty about
whether the findings are confounded by under-
reporting and other traits (14). Thus, younger people
should be informed to not expect any substantial
benefit from moderate drinking. For most older per-
sons, the overall benefits of light drinking, especially
the reduced CVD risk, clearly outweigh possible cancer
risk. For young women with no coronary disease risk
factors, the breast cancer data suggest limiting alcohol
intake to very modest amounts, but post-menopausal
women (at relatively high risk of CVD) should
consider the overall health advantage if choosing to
drink a moderate amount of alcohol daily. A similar
approach should be taken by patients with CVD (15).
Last, but not least, the results by Xi et al. (5) sup-
ported previous studies that had shown a significant
reduction in total mortality with light-to-moderate
drinking versus abstention or heavy drinking (2). The
importance of determining the effect on total mortal-
ity is clear if one considers that a layman would be less
interested in the effects of alcohol on this or that dis-
ease or clinical outcome, but more on life expectancy.
Epidemiological research is generally given a lower
place in the hierarchy of causal inference than truly
experimental research. Thus, despite the consistent
evidence from observational studies regarding the
beneficial effects of moderate alcohol consumption
on fatal and nonfatal CVD and total mortality, as
discussed here, a controlled, randomized, long-term
trial is highly desirable and appears to be feasible
(16). In the meantime, the following provisional
conclusions can be proposed:
 Regular moderate alcohol consumption protects
against fatal and nonfatal CVD and all-cause mor-
tality, both in healthy adults and in CVD patients.
 The dose-effect relationship is characterized by a
J-shaped curve.
 For light-to-moderate levels of alcohol consump-
tion, the risks of some cancers (breast, colorectal,
oral) are relatively small and should be considered
in the context of each individual global risk.
 Lifelong alcohol abstainers should not start drink-
ing for health reasons only, but should be encour-
aged to adopt healthy lifestyles (regular physical
activity, no smoking, weight control, and dietary
habits such as the Mediterranean diet).
 Excessive or irregular (binge) alcohol use is detri-
mental to human organs and function and is a
major public health and social problem.
ADDRESS FOR CORRESPONDENCE: Dr. Giovanni de
Gaetano, Department of Epidemiology and Preven-
tion, IRCCS Istituto Neurologico Mediterraneo Neu-
romed, Via dell’Elettronica, 86077 Pozzilli (Isernia),
Italy. E-mail: giovanni.degaetano@moli-sani.org.

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KEY WORDS alcohol, cancer, cardiovascular,
mortality