Harm Reduction-A Systematic Review On Effects of Alcohol Reduction On Physical and Mental Symptoms

bs_bs_banner
ORIGINAL ARTICLE doi:10.1111/adb.12414
Harm reduction—a systematic review on effects of

alcohol reduction on physical and mental symptoms
Katrin Charlet & Andreas Heinz
Department of Psychiatry and Psychotherapy, Campus Mitte, Charité – Universitätsmedizin Berlin, Germany1
ABSTRACT
Based on the knowledge that alcohol misuse causes a multitude of diseases and increased mortality, this systematic
review examines whether a reduction of the individual alcohol consumption can contribute to a minimization of health
risks within a harm reduction approach. In fact, the reviewed 63 studies indicate that interventions aiming at alcohol
reduction (including total abstinence as one possible therapeutic aim) indeed resulted in or were associated with
positive effects in harmful, hazardous or alcohol-dependent drinkers. Major benefits were observed for reducing
alcohol-associated injuries, recovery of ventricular heart function in alcoholic cardiomyopathy, blood pressure
lowering, normalization of biochemical parameter, body weight reduction, histological improvement in pre-cirrhotic
alcohol-related liver disease and slowed progression of an already existing alcohol-attributable liver fibrosis.
Furthermore, reduced withdrawal symptoms, prevalence of psychiatric episodes and duration of in-patient hospital
days, improvement of anxiety and depression symptoms, self-confidence, physical and mental quality of life, fewer
alcohol-related adverse consequences as well as lower psychosocial stress levels and better social functioning can result
from reduced alcohol intake. The reviewed literature demonstrated remarkable socioeconomic cost benefits in areas
such as the medical health-care system or workforce productivity. Individuals with heightened vulnerability further
benefit significantly from alcohol reduction (e.g. hypertension, hepatitis C, psychiatric co-morbidities, pregnancy, but
also among adolescents and young adults). Concluding, the reviewed studies strongly support and emphasize the
importance and benefits of early initial screening for problematic alcohol use followed by brief and other interventions
in first contact medical health-care facilities to reduce alcohol intake.
Keywords Alcohol dependence, harm reduction, harmful drinking, hazardous drinking, physical and mental
health, systematic review.
Correspondence to: Katrin Charlet, Department of Psychiatry and Psychotherapy, Campus Mitte, Charité – Universitätsmedizin Berlin, Charitéplatz 1,
10117 Berlin, Germany. E-mail: katrin.charlet@charite.de
INTRODUCTION influenced by diverse factors such as age, gender, familial

risk considering genetics and environment, (socio)eco-
High chronic alcohol use damages the human body. nomic status of a person and its society, culture and alco-
According to the World Health Organization, harmful hol policies (WHO 2014). For example, regarding cancer,
alcohol intake is one of the top five factors that causes even drinking as low as 8 g of pure alcohol per day or less
over 200 diseases and injuries (WHO 2014; for risk-level was associated with increased risk of female breast can-
definitions regarding alcohol intake, see Table 1). Contin- cer (Hamajima et al. 2002). The International Agency For
uous excessive alcohol intake is likely to damage organs Research On Cancer has no threshold for alcohol on cancer
and tissues, impair perception, cognition, affect and be- (IARC 2012), and the WHO (2014) refers to all alcohol
havior, and may facilitate the risk of alcohol dependence use as potentially harmful. Besides the amount of alcohol
(WHO 2014). However, there is no absolute threshold consumed, the drinking pattern also seems to play a
for alcohol consumption on some chronic harm, because crucial role in characterizing negative effects of alcohol
individual vulnerability of alcohol-attributable harm is intake and should therefore be considered in treating
© 2016 Society for the Study of Addiction Addiction Biology

2
Table 1 Definition of hazardous, harmful alcohol consumption and alcohol dependence.
Hazardous alcohol consumption Harmful alcohol consumption Alcohol dependence syndrome
© 2016 Society for the Study of Addiction

According to AWMF-guidelines A pattern of alcohol use that causes actual damage to the ICD-10 (Dilling, Mombour, & Schmidt 2014): F10.2 Diagnostic guidelines; presence
(Mann et al. 2015): consumers’ physical or mental health. Harmful alcohol of three or more of the following criteria during the previous 12 months:
• >12 g pure alcohol per day in women use is often criticized by others and may lead to diverse (1) Strong desire or sense of compulsion to take the substance (craving).
• >24 g pure alcohol per day in men negative social consequences. (ICD-10: F10.1; DSM-IV-TR: (2) Difficulties in controlling substance-taking behavior in terms of its onset,
305.00; DSM-5: F10.1-F10.2, depends on the severity) termination or levels of use.
(3) A physiological withdrawal state when substance use has ceased or have
been reduced, as evidenced by the characteristic withdrawal syndrome for the
substance or use of the same (or closely related) substance with the intention
of relieving or avoiding withdrawal symptoms.
According to the British Medical Binge drinking: (4) Evidence of tolerance, such that increased doses of the psychoactive
Association (Mundle et al. 2003): Consumption of five or more alcoholic drinks substance are required in order to achieve effects originally produced by
• >30g/day in men (i.e. 10–12 g of pure alcohol per drink) on one occasion in lower doses.
men (DHS 2010; Mann et al. 2015); four or more alcoholic (5) Progressive neglect of alternative pleasures or interests because of
According to the WHO (Mundle et al. 2003): drinks on one occasion in women, respectively (Mann et al. psychoactive substance use, increased amount of time necessary to obtain or
• >20g/day in women 2015). Caution has to be paid to existing differences between take the substance or to recover from its effects.
• >40g/day in men countries’ definitions; e.g. according to Australian Alcohol (6) Persisting with substance use despite clear evidence of overtly harmful
Guidelines (2001), binge drinking is defined similarly for consequences. (cf. DSM-IV-TR: 303.90; DSM-5: F10.1-F10.2, depends on the
According to the British Health Education women’s quantity but higher for men (i.e. intake of six or severity)
Council (1994) (source: Kurz 2012): more alcoholic drinks per occasion).
• >60g/day in men
Addiction Biology
Effects of alcohol reduction 3
alcohol-related problems (e.g. Wannamethee & Shaper METHODS

1991; Seppä, Laippala, & Sillanaukee 1994; Wetterling
Data sources
et al. 1999; Miller, Plant, & Plant 2005).
Contrary to earlier opinions that alcohol-dependent To investigate alcohol reduction effects on primary
individuals should only aim at total abstinence, physical and mental symptoms (and exploratory on other
nowadays intervention strategies widened toward the effects such as economic consequences), we conducted a
reduction of alcohol intake as stated by the European systematic literature review during May 2013. Relevant
Medicines Agency in 2010 (Mann & Körkel 2013). studies were identified by searching the PUBMED
However, while moderate, low-risk drinking may be a database using the following search terms: alcohol,
reachable aim for some people with harmful use, it may ethanol, controlled drink*, controlled alcohol intake,
be difficult to be established for alcohol-dependent controlled alcohol consumption, reduc* alcohol, decreas*
subjects (Sobell & Sobell 1995b; Mann et al. 2005; alcohol, alcohol reduction, alcohol moderation, alcohol
Guardia-Serecigni 2011). Other addiction experts also minimization. Study references of selected articles were
refer to difficulties of intervention programs such as additionally reviewed and taken into account when of
Controlled Drinking in alcohol-dependent subjects, relevant information gain.
because loss of control over the alcohol intake is one of
the central diagnostic criteria according to the
Study selection
International Statistical Classification of Diseases and Related
Health Problems (ICD-10; Table 1). Thus, maintaining a Because this is the first systematic review on this topic,
fixed drinking plan or drinking by rules seems paradox we included randomized controlled trials and non-
per definition (Bottlender, Spanagel, & Soyka 2007). On randomized trials (prospective and retrospective cohort
the other hand, research findings like those reported from studies, case-control studies) as well as meta-analyses
the longitudinal Project MATCH supported by the without time limitation. Exclusion criteria were studies
National Institute on Alcoholism and Alcohol Abuse showed on non-human data, studies published in another
that also alcohol-dependent people with loss of control language than English or German, studies on other
over more than the past 12 months can constantly beverages than alcohol, and alcohol-related studies not
reduce their drinking (Witkiewitz 2008). As an investigating the association between reduction of
alternative to total abstinence, programs aiming at harm alcohol intake and effects on physical or mental
reduction may help to establish self-determined controlled symptoms. If studies only reported units or standard
drinking and may use this as a bridge toward long-term drinks of alcohol without a clearer ethanol content
complete abstinence (Mann & Körkel 2013). Here, harm definition, studies were also excluded due to lack of
reduction refers to minimizing acute harm that comes comparability. Further, trials using pharmacologic
along with alcohol intoxication including health as well approaches of alcohol reduction were excluded because
as legal and social issues (Toumbourou et al. 2005). Such of difficulties in differentiating, interpreting and
intervention approaches provide a reduction of the total comparing observed outcome effects (e.g. somatic
amount of alcohol consumption and modifications of changes) of reduced alcohol intake. Also, in this review,
the drinking pattern, e.g. establishment of ‘secure’ we did not distinguish the effects of various kinds of
drinking (less alcoholic drinks per occasion, less drinking alcohol, because literature on this specific topic reports
occasions at all, abstinence with short episodes of re- inconsistent findings or no significant differences,
duced alcohol drinking and ‘do not drink and drive’ rules respectively (cf., Hanaoka et al. 1994; Smith-Warner
(cf., Sitharthan et al. 1997; Shaw et al. 1998; Whitlock et al. 1998; Joosten et al. 2011). Because this review
et al. 2004); for adolescents and young adults, other spe- focuses only on the effects of any alcohol reduction
cific programs were developed (cf. McBride et al. 2004; (except by pharmacological intervention) on physical,
Moreira et al. 2009; Newton et al. 2009; Vogl et al. mental or other exploratory outcome measures (e.g.
2009; Wachtel & Staniford 2010; Newton et al. 2011). economic effects), diverse applied psychological
However, here, an intermediate step is still missing in treatments within the reviewed studies (e.g. brief
this field: the investigation of specific dose–response effects interventions of various frequency or time frames,
following alcohol reduction. To date, only a few studies physicians’ advise, motivational interviewing techniques,
(e.g. Maheswaran, Beevers, & Beevers 1992; Kawano cognitive-behavioral therapy, cue exposure treatment, in-
et al. 1998; Nicolás et al. 2002; Vogl et al. 2009) investi- patient or out-patient treatment, group or individual ses-
gated such direct health outcomes of reduced alcohol sions) are subsumed as intervention or treatment without
consumption. Therefore, this systematic review may help further description. Further, no detailed gender-specific
to compare and discuss these findings in order to specify information about outcome variables are reported, except
treatment aims in harm reduction approaches. for the domain of harm reduction in pregnancy or if there

4 Katrin Charlet & Andreas Heinz
were only gender-separated data available. Because of 3 What kind of population has been investigated? Here,
reasons of parsimony, wherever given, gender-combined we report whether trials included patients who were
outcome effects are reported. In prospective studies, diagnosed with alcohol dependence or not.
longest follow-up results are reported, as long as effect 4 Do the trials only include self-reported alcohol
tendencies were stable between different time points of consumption measures or were other verifying
the observation period (i.e. increasing or decreasing); methods used?
otherwise, results were discussed in more detail.
RESULTS
Extraction and quality assessment
Search results
Abstracts were screened for relevance and extracted by the The initial search strategy identified a total of 2129
reviewer KC, and selected articles were discussed between articles of which 53 were considered potentially relevant.
the two reviewers (KC and AH). Also, in the event of uncer- Additionally, 28 studies were identified through
tainty regarding the relevance of a study according to the screening the reference lists of selected articles. Of those,
selection criteria described previously detailed, study 18 articles were excluded due to reasons shown in Fig. 1.
characteristics were discussed between the two reviewers Altogether, 63 articles were included (Table 2; Appendix
(KC and AH). Decisions on study selection were 1). A flow diagram of the inclusion of studies according
documented. We further paid specific attention to the fol- to the PRISMA group (Moher et al. 2009) is presented
lowing questions or issues within the reviewed studies: in Fig. 1. Because our systematic literature search was
1 Do the reviewed studies describe correlational findings limited to the earlier listed terms, we are aware that
between alcohol reduction and physical or mental out- beyond the identified 2129 articles there are even further
come measures or do trials describe prospective, relevant studies and meta-analyses not found by this
longitudinal (pre-treatment/post-treatment) changes? systematic search (some of which were pointed out by
2 How strongly was alcohol intake reduced? In order to reviewers and helpful comments).
provide comparability across studies, we report the
respective amount of alcohol use in grams of pure
Effects of alcohol reduction on hospitalization, injuries
alcohol. Therefore, we converted the reported
and mortality rates
alcohol intake from units to the given equivalent of
grams of pure alcohol, or converted given alcohol We identified three meta-analyses (Di Castelnuovo et al.
standard unit volumes in milliliters into alcohol 2006; Ronksley et al. 2011; Rehm & Roerecke 2013)
amounts in grams of pure alcohol by multiplying and six prospective randomized controlled studies (RCTs)
the milliliters by 0.8 (WHO 2014), respectively. (Persson & Magnusson 1989; WHO Brief Intervention
Figure 1 Flow diagram of the selection process of studies for the systematic review on effects of alcohol reduction on physical and mental
symptoms, according to Moher et al. (2009)

Table 2 Summary of the characteristics of 59 studies included for investigation of the effects of alcohol reduction on physical and mental health measures in adults.
Total
follow-up Age Study sample (inclusion
Study Study design period (years) criteria for alcohol use, if given) Alcohol use measures Outcome measures
Xin et al. 2001 Meta-analysis 2.2 years 27–57 N = 2234 Daily alcohol consumption Average net change in systolic
and diastolic blood pressure,
Mean body weight change
Di Castelnuovo Meta-analysis 10 years All ages N = 1,015,835 Daily alcohol consumption Total mortality

et al. 2006
Koppes et al. Meta-analysis 12 years 18–85 N = 369,862 Daily alcohol consumption Type 2 diabetes risk
2005
Ronksley et al. Meta-analysis 35 years 15–104 N = 458,811–1,925,106 Daily alcohol consumption Overall mortality from
2011 (mean 11 years) (varies between number cardiovascular disease,
of pooled studies for Incidence and mortality from
each outcome) coronary heart disease,
Incidence and mortality from
stroke
Roerecke & Meta-analysis — 18–75 N = 50,031 Irregular heavy-drinking Incidence of ischaemic heart
Rehm 2010 episodes disease morbidity and mortality
Longnecker Meta-analysis — Not given Not given Daily alcohol consumption Breast cancer risk
1994
Patra et al. Meta-analysis — Not given Differed depending Daily maternal alcohol Low birth weight,
2011 on birth outcomes: consumption Preterm birth,
277,300–280,443 Small for gestational age
pregnant mothers,
20,582 children
with low birth weight,
12,888 preterm birth,
8679 SGA infants
Rehm & Pooled analysis 1 year Not given Not given Daily alcohol consumption All-cause mortality
Roerecke 2013
Smith-Warner Pooled analysis 11 years 34–76 N = 322,647 Daily alcohol consumption Invasive breast cancer risk
et al. 1998
Lönnroth et al. Systematic — Not given N = 167,654 Daily alcohol consumption Tuberculosis risk
Effects of alcohol reduction
2008 review and

pooled analyses
Addiction Biology
5
6
Table 2. (Continued)
Total
Ueshima et al. RCT 3 weeks 30–59 N = 54 (men only: Daily alcohol consumption Systolic and diastolic blood
1993 (included in ≥28 ml ETOH/>4× pressure,
meta-analysis per week) Body weight,
by Xin et al. 2001) Biomarkersa

Kawano et al. RCT 4 weeks Not given N = 34 (≥30 ml or Daily alcohol consumption Office and ambulatory systolic
1998 (included in 24 g ETOH per day)b and diastolic blood pressure,
meta-analysis Quality of sleep

by Xin et al. 2001)
Cox et al. RCT 4 weeks 20–45 N = 75 (men only: >210 ml or Weekly alcohol consumption Systolic and diastolic blood
1993 (included in 168 g ETOH per week)b pressure, heart rate,
meta-analysis Body weight,
by Xin et al. 2001) Physical fitness and oxygen uptake,
Biomarkersa
Parker et al. RCT 6 weeks Mean (SD) only: N = 59 (men only: >210 ml or Weekly alcohol consumption Systolic and diastolic blood
1990 (included in 51.9 (1.4) 168 g ETOH per week)b pressure, heart rate,
meta-analysis Tea and coffee consumption,
by Xin et al. 2001) smoking and physical activity,
Biomarkersa
Maheswaran RCT 8 weeks Mean (SD) only: N = 41 men only; Weekly alcohol consumption Systolic and diastolic blood
et al. 1992 (included in 43.5 (2.4)–45.7 (3.2) excluding alcohol-dependent pressure, pulse rate,
meta-analysis individuals Body weight, smoking and
by Xin et al. 2001) caffeine intake,
Biomarkersa
Rakic et al. RCT 12 weeks 21–65 N = 55 (210–500 ml ETOH Weekly alcohol consumption, Ambulatory systolic and
1998 (included in per week or 168–400 g Regular daily or diastolic blood pressure,
meta-analysis ETOH per week)b predominantly heart rate,
by Xin et al. 2001) weekend drinking Body weight,
Dietary nutrient intake,
smoking and physical activity
Colman et al. RCT 12 weeks mean (SD) only: N = 40 Daily alcohol consumption Histological, biochemical and
1980 48.2(9)–48.8(9.9) hematological changes in
pre-cirrhotic liver disease
Addiction Biology
Total
Puddey et al. RCT 14 weeks 25–55 N = 46 (men only: >210 ml or Weekly alcohol consumption Systolic and diastolic blood
1985 (included in 168 g ETOH per week)b pressure, pulse rate,
meta-analysis Frequency of exercise, body
by Xin et al. 2001) weight, dieting, smoking and

anxiety,
Biomarkersa
Puddey et al. RCT 18 weeks 25–70 N = 86 (men only: >210 ml or Weekly alcohol consumption Systolic and diastolic blood
1992 (included in 168 g ETOH per week)b pressure, heart rate,
meta-analysis Dietary intake,
by Xin et al. 2001) Smoking, physical activity and
body weight,
Biomarkersa
Heather et al. RCT 6 months 18–65 N = 104 (men: 280 g ETOH per week; Last month’s alcohol Physical health,
1987 women: 160 g ETOH per week consumption, Well-being,
and/or one positive response Heaviest month’s alcohol Control of drinking problems,
on questions of alcohol-related problems) consumption Biomarkers (GGT and mean
corpuscular volume)
Sitharthan RCT 6 months >18 N = 42 alcohol-dependent Frequency of alcohol Severity of alcohol dependence,
et al. 1997 patients only consumption, Self-efficacy and control over
Alcohol consumption per alcohol consumption,
occasion Problems associated with
alcohol
WHO Brief RCT 9 months 18–70 N = 1169 (men: >50–120 g Daily alcohol consumption, Social consequences of
Intervention ETOH per day; women: >32–80 g Intensity of drinking on drinking (injuries to themselves
Study Group ETOH per day) typical drinking days (e.g. or others, legal problems and
1996 number of drinks), unemployment),
Frequency of alcohol Concerns expressed by others,
consumption Alcohol dependence symptoms
Wallace et al. RCT 12 months 17–69 N = 929 Weekly alcohol Systolic and diastolic blood
1988 (included in (men: ≥315 g ETOH consumption, pressure,
meta-analysis per week, women: ≥189 g Proportions of patients with Frequency of exercise, body
by Xin et al. 2001) ETOH per week) excessive alcohol weight, dieting, smoking,
consumption Biomarkersa
Addiction Biology
7
8
Total
Liu et al. 2011 RCT 12 months 18–65 N = 616 Weekly alcohol consumption, Alcohol problems (problems at
(included in (all male) (>168 g Frequency of drinking days, work/school, with family/friends,
meta-analysis ETOH per week), Heavy drinking episodes (≥5 legal consequences or
by Rehm & including alcohol-dependent drinks per occasion) alcohol-associated injuries),

Roerecke 2013) patients Health-care utilization
(hospital days and emergency
department visits),
Special treatment for alcohol
problems
Fleming et al. RCT 12 months 65–75 N = 146 Weekly alcohol consumption, Health status (smoking,
1999 (men: ≥132 g ETOH per week Binge drinking episodes, accidents, injuries),
or binge drinking Binge drinking proportion, Use of health-care services
with ≥4 drinks per Weekly excessive drinkingc (hospital days and emergency
occasion for 2×/last department visits)
3 months; women: ≥96 g
ETOH per week or ≥3
drinks per occasion for
2×/last 3 months)
Persson & RCT 12 months 15–70 N = 78d Weekly alcohol consumption Biomarkers,e
Magnusson (men: 200 g ETOH per week; Sickness allowance days,
1989 women: 150 g ETOH per week; Hospitalization,
or GGT > 0.6 μkat/l) Consultations to out-patients
clinics
Scott & RCT 12 months 17–69 N = 72 Weekly alcohol consumption Psychological well-being (e.g.
Anderson (women only: >210–700 g general health, life
1991 ETOH per week) quality/satisfaction, affect
balance and anxiety),
Consultation or episode rates,
Frequency of exercise, body
weight, dieting, smoking,
Biomarkersf
Addiction Biology
Total
Anderson & RCT 12 months 17–69 N = 154 Weekly alcohol consumption Psychological well-being (e.g.
Scott 1992 (men only: >350–1050 g general health, life
ETOH per week) quality/satisfaction, affect
balance and anxiety),

Consultation or episode rates,
Frequency of exercise, body
weight dieting and smoking,
Biomarkersf
Longabaugh RCT 12 months >18 N = 447 Heavy drinking days Negative consequences from
et al. 2001 (BAC ≥ 0.003 mg/dl, (≥6 drinks of 10 g ETOH per drinking (physical, intrapersonal
or alcohol intake 6 hours occasion) and interpersonal consequences,
prior to injury) social responsibility and
impulse control)
Potamianos RCT 12 months 18–60 N = 151 Daily alcohol consumption Severity of alcohol dependence,
et al. 1986 (≥80 g ETOH per day during Neurotic psychopathology,
heavy-drinking periods) Physical symptoms,
Biomarkers (GGT and mean
corpuscular volume)
Sitharthan RCT 12 months >18 N = 91 Weekly alcohol consumption, Severity of alcohol dependence,
et al. 1996 alcohol-dependent Drinking days per week, Self-efficacy and control over
patients only Usual number of alcohol consumption,
consumed drinks, Problems associated with
Consumption of ≥10 alcohol
or 15 drinks,
Longest period of continuous
drinking,
Longest period below three
drinks per day
Brown 1980 RCT 12 months Mean (SD) only: N = 60 Abstinent days, Drinking and driving episodes,
30.15 (7.12)– (men only: Controlled drinking days Psychosocial adjustment
34.20 (11.54) BAC ≥ 0.20%) (≤80 g ETOH per day), (domestic, vocational,
Uncontrolled drinking days interpersonal, social and

(≥80 g ETOH per day) health status)
Addiction Biology
9
10
Total
Fitzgerald & RCT 12 months Only given: N = 354 Abstinence/abstinent days Quality of life
Mulford 1985 <30 to 60+ alcohol-dependent after discharge,
patients only Change in drinking pattern,
Denied drinking >5 drinks
within 2 hours since

discharge,
Days prior to first drink after

discharge,
Days of longest dry period
after discharge
Kraemer RCT 12 months mean (SD) only: N = 213 Daily alcohol consumption, Health-related quality of life,
et al. 2002 44.6 (15.3)–49.3 (14.3) (men: >227 g ETOH Monthly alcohol consumption, Physical and mental health,
per week, women: >170 g Monthly abstinent days Alcohol-specific adverse
ETOH per week, or consequences (interpersonal,
AUDIT score >8) intrapersonal, social, physical,
impulsive behavior)
Chang RCT Approximately 18–43 N = 250 Prenatal (pre-assessment) Birth outcome (birth weight,
et al. 1999 12 monthsg (pregnant women screened alcohol consumption/ Apgar score of infant)
positive of risk drinking drinking day,
in pregnancy) Antepartum alcohol
consumption/drinking day,
Drinking episodes
Lieber et al. RCT 2 years Group means (SDs) only: N = 789 Daily alcohol consumption Progression of alcohol-induced
2003 intervention 48.8 (8.2), (≥80 g ETOH per day for fibrosis (histological, biochemical
control 48.8 (9.1) ≥5 years and significant changes)
alcoholic liver disease)
Lang et al. RCT 2 years Mean (SD) only: 43 (7) N = 129 Difference between initial and Systolic and diastolic blood
1995 (included in (excessive drinkers as indicated follow-up monthly alcohol pressure,
meta-analysis by a GGT value >1.5× the consumption Antihypertensive treatment,
by Xin et al. 2001) upper limit of the normal range) Difference between initial and
follow-up body mass index,
Absenteeism for illness and
accidents,
Biomarkersa
Addiction Biology
Total
Cushman RCT 2 years 21–79 N = 641 Daily alcohol consumption Incidence or recurrence of
et al. 1998 (included in (≥294 g ETOH per week) hypertension,
meta-analysis excluding alcohol-dependent Systolic and diastolic blood
by Xin et al. 2001) individuals pressure, heart rate,
Physical activity, body weight,

dietary and smoking,
Biomarkersa
Manwell RCT 2 years 18–40 N = 454 Weekly alcohol consumption, Health-care utilization
et al. 2000 (>132–672 g alcohol per Binge drinking in the past (hospital days and emergency
week, or >4 drinks per month, department visits),
occasion, or ≥2 positive answers Excessive drinking in the past Changes in health status
to the CAGE questionnaire) week (smoking, depression,
accidents and injuries)
Fleming RCT 4 years 18–65 N = 774 Weekly alcohol consumption, Motor vehicle and legal events
et al. 2002 (men: >168 g ETOH per week, Binge drinking episodes per Accidents and injuries,
women: >132 g ETOH per week; month, Health-care utilization (hospital
or >5 drinks per occasion Number of heavier drinking days and emergency
during previous 30 days) persons, department visits),
Number of persons reporting Health status, Mortality,
binge drinking Health care and societal costs
Howes 1985 Open, crossover, 4 days 25–41 N = 10 (average intake of Daily intake of 80 g ETOH or Systolic and diastolic blood
randomized study 10–40 g ETOH per day) abstinence pressure
Hsieh Quasi-experimental 4 weeks Mean (SD) only: N = 29 Daily alcohol consumption Systolic and diastolic blood
et al. 1995 trail 48.8 (6.32)–52.4 (6.41) pressure,
Biomarkersa
Craig et al. Prospective cohort 10 days Mean (SD) only: N = 405 Daily alcohol consumption, Subjective state of withdrawal
2011 study 41.7 (10) alcohol-dependent BAC or drunkenness
patients only
Yamada Prospective cohort 4 weeks 35–59 N = 40 Weekly alcohol consumption Biomarkers,a
et al. 1997 study (60–80 ml ETOH per day or Systolic and diastolic blood
48 g to 64 g ETOH per day, pressure
respectively)a
Addiction Biology
11
12
Total
Shaw Prospective cohort 12 months Group means (SDs) only: N = 160 6-month alcohol consumption, Anxiety, depression, self-esteem
et al. 1998 study 43.09 (1.25)–44.95 (1.52) alcohol-dependent patients only Drinking statush and satisfaction with life situation,
Level of social stability, marital
status and employment,
Use of health and social resources,

Social and physical
complications of drinking
Little Prospective cohort 12 months <20–≥40 N = 400 Daily maternal alcohol intake Infants exposure to alcohol,
et al. 1989 study (means (CIs): 28 mother–child pairs (‘heavier’ during 3 month after delivery, Infants development (mental
(27.4–28.6)–31 drinking mothers with intake of Frequency of binge drinking and psychomotor development)
(30.1–31.7)) ≥23.68 g ETOH per day during during 3 month after delivery
nursing or binge drinking of
≥59.2 g ETOH per occasion; lighter
drinking mothers with daily
intake below heavier drinkers during
nursing, including non-drinkers)
Balkau Prospective cohort 3 years 30–65 N = 63 Daily alcohol consumption Biomarkers,a
et al. 2006 study Systolic and diastolic blood
pressure,
Physical activity,
Body weight, body mass index,
Smoking
Nicolás Prospective 4 years <60 N = 65 Daily alcohol consumption Nutrition,
et al. 2002 cohort study (alcohol-dependent patients: Cardiac status (left ventricular
>100 g ETOH per day for at ejection function, shortening
least 10 years) fraction, cardiac contractility,
end-diastolic and end-systolic
diameters and left ventricular mass)
Joosten Prospective 4 years 40–75 N = 38,031 Change in daily alcohol Type 2 diabetes risk,
et al. 2011 cohort study consumption Biomarker (adiponectin and
hemoglobin A1C)
Addiction Biology
Total
Hulse & Tait Prospective 5 years 18–64 N = 236i alcohol-dependent Days of sobriety Hospital morbidity (frequency
2003 cohort study patients only of hospital events, length of
stay, time to first hospital event
and time to first
alcohol-related event),

Mental health morbidity
(frequency of mental health
episodes, length of stay and
time to first mental health event)
Coles Prospective About Means (SDs) only: N = 68 mother–child pairs Prenatal weekly alcohol Birth weight,
et al. 1991 cohort study 6.7 yearsj mothers/caretakers exposure, Head circumference,
31.0 (4.58)–33.71 Prenatal binge drinking Weight, height,
(5.01), children 5.3- Gestational age,
8.9 (no SDs given) Apgar score at 1 and 5 minutes
after birth,
Score on Obstetrical
Complications Scale,
Neonatal alcohol dysmorphia score,
Cognitive development and
academic functioning,
Adaptive behavior
Sesso et al. Prospective 7 years 40–84 N = 18,455 Daily alcohol consumption, Risk of cardiovascular disease
2000 cohort study 7 years change in weekly events (myocardial infarction,
alcohol consumption angina pectoris, coronary artery
bypass graft surgery, percutaneous
transluminal coronary
angioplasty, stroke and cancer),
Cardiovascular disease-related
death
Robinson Prospective 14 years <20–35+ N = 2868 Maternal alcohol consumption Child behavior (total behavior,
et al. 2010 cohort study mother–child pairs (i.e. total number of drinks internalizing behavior and
consumed per week externalizing behavior)

in the first 3 months of
Addiction Biology
13
pregnancy)
14
Total
Mann et al. Prospective 16 years 20–63 N = 96 alcohol-dependent Drinking patternk Hospitalization,

2005 cohort study patients only Out-patient treatment,
Death rates

Gual Prospective 20 years Mean (SD) only: N = 850 alcohol-dependent Drinking statusl Mortality rate,
et al. 2009 cohort study 39.0 (9) patients only Morbidity rate (presence of
chronic illnesses and use of

medication),
Accidents (home, work and
traffic),
Unemployment,
Long-term disability,
Financial and legal problems,
Emergency unit visits,
Hospital admissions,
Psychosocial stress and social
functioning
Rehm et al. Epidemiological — 20–64 Not given Daily alcohol consumption Mortality (alcohol attributable),
2011 study (cross-sectional) Deaths (death by alcohol-related
injury)
Hanaoka et al. Case-control study — <85 N = 282 Weekly alcohol consumption, Esophageal cancer risk
1994 Frequency of alcohol drinking,
Type of alcoholic beverage
consumed
Borges et al. Case-crossover — >18 N = 4320 Alcohol use during the 6 Risk of injury (unintentional
2006 study (cross-sectional) hours prior to the injury, injuries,
Alcohol use during same day intentional self-inflicted injuries
in the previous week and intentional injuries inflicted
by others)
Addiction Biology
Total

Magnus et al. Estimate analysesm — >15 N = 11,337,478n Modeling of ‘2 separate levels Lifetime health benefits (fewer
2012 (cross-sectional) of realistic incident cases of alcohol-related
reduction targets’: disease, deaths,
(1) An ideal (equivalent to and disability adjusted life years),
3.4 l reduction Workforce production costs,
annually per capita) and Household production and leisure
(2) A progressive target time costs,
reflecting Health sector costs
a shorter-term goal set as half of
the ideal reduction target (1.7 l
per capita)
RCT = randomized controlled trial; ETOH = ethanol; GGT = serum gamma glutamyl transferase; BAC= breath alcohol concentration; AUDIT = Alcohol Use Disorder Identification Test (Babor et al. 2001); CAGE questionnaire (Ewing 1984);
SGA = small for gestational age; CI = 95% confidence interval. aFor details about the assessed biomarkers, please see Table 3. bConsumption amounts given in milliliters (ml) were converted in grams of ethanol by multiplication by 0.8 according
to WHO (2014). cThat is, 240 g ETOH in men and 156 g ETOH in women. dData on changes of alcohol consumption over time were only assessed for individuals in the intervention group (n = 36). eThat is, GGT, serum aspartate aminotransferase,
alanin-aminotransferase, blood ethanol, serum triglcerides, creatinine and urate in serum, mean cell volume, hemoglobin, erythrocyte volume fraction, serum cholesterol. fThat is, GGT and mean red cell corpuscular volume, BAC. gNo specific follow-
up period given; 12 months follow-up period is approximated based on the information of study inclusion of pregnant women initiating prenatal care (i.e. 1 week of gestational age) to study follow-up assessment at an average of 57.2 weeks (±34.9)
days after delivery (i.e. 40 weeks/10 months of pregnancy plus about 2 months). hCategories of drinking status were total abstinence (no further definition), controlled social drinking (not more than three drinking occasions per week, not more than
54 g ETOH per occasion, mean = 36 g ETOH per week at 6 months and 1 year), greatly improved (consumption reduced by 75% or more, mean reduction = 87% at 6 months, 90% at 1 year), slightly improved (consumption reduced by 50–74%,
mean reduction = 63.5% at 6 months, 63% at 1 year), unchanged (a failure to achieve any of the aforementioned criteria). iSample sizes are referred to the combined intervention groups (n = 118) and matched control group (n = 118). jStudy
included women’s intake during pregnancy and children’s outcome at mean age of 5 years and 10 months. k‘Improved’ drinking behavior (reduced alcohol intake to <60 g alcohol per day in men and <30 g alcohol per day in women), ‘unimproved’
drinking behavior (subjects who did not fulfill the criteria of the improved drinking behavior or who had meanwhile developed an additional dependence on or abuse of other drugs) or ‘abstinent’ (no alcohol at all during 12 months before questioning
or only one relapse of less than 1-week duration). lBased on reported quantity and frequency of alcohol consumption, drinking status was defined as heavy-drinking patient (i.e. ≥50 g ethanol per occasion or daily drinking), controlled drinking patients
(<50 g ethanol per occasion with ≥1 occasion per month but less than daily drinking) or abstinent patients (up to 50 g ethanol per occasion with 0–1 occasion per month). mEstimate analyses were based on data derived from 2004–2005 National
Health Survey (NHS), 2003 Australian Burden of Disease, 2000–2001 Disease Costs and Impact Study, 2004–2005 NHS Confidentialised Unit Record Files and 2006 ABS Time Use Survey. nWorkforce production gains were modeled on a theoretical
cohort of Australians (aged 15–65 years); for other estimates, please see Magnus et al. (2012).
Addiction Biology
15
Study Group 1996; Fleming et al. 1999, 2002; epidemiological (cross-sectional) study already an
Longabaugh et al. 2001; Liu et al. 2011), of which only increase in absolute death rates in relation to an average
the RCT conducted by Liu et al. (2011) was already alcohol use, but already beyond an amount of 10 g
included in the meta-analysis of Rehm & Roerecke alcohol per day. Also, an exponential association beyond
(2013). Because the RCT by Liu et al. (2011) adds inter- that amount was observed between lifetime risk of
esting findings beyond the scope of the meta-analysis on alcohol-attributable injuries and daily alcohol intake in
all-cause mortality and its relation to consumed alcohol Europeans of ages 15 years and above (Rehm et al. 2011).
(Rehm & Roerecke 2013), we report this RCT, too. Addi- In regard of alcohol-related problems (including legal
tional findings on the topic were derived from two pro- problems, problems at work/school or with
spective cohort studies (Mann et al. 2005; Gual et al. family/friends) and non-fatal self-injuries or injuries to
2009) and three studies using cross-sectional data ap- others, three RCTs found no effects past significant
proaches (Borges et al. 2006; Rehm et al. 2011; Magnus reduction of alcohol amount by 7% to 36% (WHO Brief
et al. 2012) (for study details please see also Table 2). Intervention Study Group 1996; Fleming et al. 1999),
For total mortality, given observations reported a J- or lower frequency of drinking days by 36% (Liu et al.
shaped dose–response of consumed alcohol in the general 2011), or restriction of heavy drinking episodes with
population for a median follow-up period of 10 years (Di more than 48–60 g of ethanol by 46% to 47% (Fleming
Castelnuovo et al. 2006) or an average of 11 years et al. 1999; Liu et al. 2011), or limited weekly excessive
(Ronksley et al. 2011). Overall, light to moderate drinking drinking (<240 g ethanol in men or 156 g in women)
was found to be associated with an beneficial lowering of by 48% (Fleming et al. 1999), respectively, over the
relative mortality risk by 16–19% (dependent on adjust- follow-up periods of 9 months (WHO Brief Intervention
ments for social status and/or dietary markers; Di Study Group 1996) and 12 months (Fleming et al.
Castelnuovo et al. 2006) or a 17% lower all-cause mortal- 1999; Liu et al. 2011). Contrary, two other RCTs found
ity (Ronksley et al. 2011) compared with non-drinking. long-term significant decreases of total, alcohol-related
While mortality risk was lowest at 6 g ethanol per day and medically treated injuries (Longabaugh et al. 2001)
(Di Castelnuovo et al. 2006) or within the range of 2.5– and fewer sickness allowance days by 44% (Persson &
14.9 g ethanol per day according to Ronksley et al. Magnusson 1989) accompanied by individual reduction
(2011), this observed relationship reverts at daily alcohol of weekly alcohol intake by 29–35% (Persson &
intake of more than 42 g ethanol per day (Di Castelnuovo Magnusson 1989) or 12% decrease of heavy drinking
et al. 2006) or >60 g ethanol per day (30% risk increase (i.e. ≥ 60 g pure alcohol per occasion; Longabaugh et al.
of all-cause mortality; Ronksley et al. 2011), respectively. 2001) over the time course of 1 year (Longabaugh et al.
Another meta-analysis resembles this critical amount of 2001), 2 years (Persson & Magnusson 1989) or 4 years
alcohol intake and reports that especially high-risk (Fleming et al. 2002), respectively. Correspondingly, a
drinkers beyond this critical point may benefit from an case cross-over study reported an additional dose–
alcohol limitation to this cut-off in regard of their mortal- response relationship that indicated that already one
ity risk (Rehm & Roerecke 2013). Here, the mortality risk and each additional alcoholic drink of 12.8 g ethanol
may decline threefold, if a person with a usual alcohol 6 hours prior to injury treated in emergency departments
intake of 96 g pure alcohol per day would diminish daily were associated with a 25% increased risk of non-fatal
drinking down to 36 g pure alcohol compared with a injuries (e.g. intentional and unintentional injuries like
person with a constant daily intake of 60 g of pure falls, trips, traffic accidents or violence) (Borges et al.
alcohol (Rehm & Roerecke 2013). This is also supported 2006). Further harm reduction effects—but only in the
by both long-term prospective cohort studies (Mann intervention groups—were reported for legal problems
et al. 2005; Gual et al. 2009), where, on one hand, and fewer but non-significantly reduced motor vehicle
significantly more heavy-drinking patients (15% after events (crashes with and without fatalities, property
10 years and 39.1% after 20 years follow-up) died damage and moving violations) along with 15–30% less
compared with 7.5%/21.7% of the controlled drinking alcohol intake (Fleming et al. 2002), and significant
patients and 5.3%/19.7% abstinent patients after 10 or changes in negative consequences from drinking such
20 years, respectively (Gual et al. 2009; for drinking as intrapersonal and interpersonal consequences, social
status definition, see Table 2). On the other hand, Mann responsibilities and impulse control together with the
et al. (2005) found that significantly more relapsed aforementioned observed alcohol reductions by 12%
patients died prematurely at the mean age of 48 years (Longabaugh et al. 2001). However, both findings
(mainly from heart attack or heart failure) compared pointing to the fact that these specific improvements were
with patients without relapses within the 16 years more likely attributable to behavior-changing effects of
observation period (73% versus 30%). For general the specific treatment method than to alcohol reduction
population, Rehm et al. (2011) showed in their only.

Concerning individual health status (e.g. tobacco use, women, but excluding drinkers with a consumption
alcohol dependence symptoms) or hospitalization days, exceeding 120 g ethanol per day in men and 80 g etha-
emergency visits or out-patient consultations, respec- nol per day in women) (WHO Brief Intervention Study
tively, four RCTs found no significant changes following Group 1996), most RCTs included heavy drinkers who
alcohol restriction (WHO Brief Intervention Study Group exceeded a weekly alcohol use of 132–200 g ethanol in
1996; Fleming et al. 1999; Persson & Magnusson 1989; men (Persson & Magnusson 1989; Fleming et al. 1999,
and in part also Liu et al. 2011), but some because of 2002; Liu et al. 2011) and 96–150 g ethanol per week
sparse incidence (Persson & Magnusson 1989; Fleming in women (Persson & Magnusson 1989; Fleming et al.
et al. 1999). Also, one prospective cohort study found 1999, 2002). Regarding the investigation of alcohol
no further differences in rates of morbidity (i.e. chronic restriction in alcohol-dependent patients, only one RCT
illnesses), hospitalization or emergency care between (Liu et al. 2011) as well as both prospective cohort stud-
patients who reduced their alcohol intake and those ies (Mann et al. 2005; Gual et al. 2009) and a case-
who remained drinking, except for prevalence of crossover study (Borges et al. 2006) followed diagnosed
respiratory illnesses, which was significantly higher in alcohol-dependent patients. Liu et al. (2011) performed
heavy drinkers than in abstainers at 20 years follow-up additionally separated data analyses of outcome mea-
(Gual et al. 2009). Contrary, Mann et al. (2005) reported sures for heavy drinkers and alcohol abusers as one
in their prospective cohort study that those ones, who group and alcohol-dependent patients (about 50% of
abstained alcohol at least 12 months prior the 16 years the total sample) as another group, which yielded similar
follow-up, experienced significantly fewer hospitalizations results of significant alcohol reductions in both groups
than patients who relapsed (18% versus 43%) and less but without significant further effects. Other studies ex-
out-patient alcohol treatment during the time course cluded alcohol-dependent patients or individuals with
(6% versus 30%). Other RCTs observed 37% fewer former alcohol treatment in the past year or alcohol
hospitalizations, 20% fewer emergency room visits withdrawal in the past (Persson & Magnusson 1989;
(Fleming et al. 2002) and (unlike Mann et al. 2005) WHO Brief Intervention Study Group 1996; Fleming
6.2% higher attendance at additional alcohol treatment et al. 1999, 2002; Longabaugh et al. 2001). No explicit
(albeit low total incidence rates; Liu et al. 2011), but information whether or not alcohol-dependent patients
again these harm reduction effects were only found in were included were provided for the meta-analyses of
intervention patients compared with control subjects Di Castelnuovo et al. (2006); Ronksley et al. (2011) and
while both groups lowered alcohol use similarly, Rehm and Roerecke (2013), or in the epidemiological
indicating that not alcohol reduction itself (rather study by Rehm et al. (2011) or the study by Magnus
modulating behavior via intervention) reduced these et al. (2012).
events (Fleming et al. 2002; Liu et al. 2011). Most original studies used established self-reported
However, for these described effects of alcohol measures of drinking behavior (WHO Brief Intervention
reductions, accompanied economic cost benefits were Study Group 1996; Fleming et al. 1999, 2002;
evaluated for the US-American society: significant Longabaugh et al. 2001; Mann et al. 2005; Liu et al.
health-care savings of $US712 and even larger 2011), e.g. Timeline Followback (Sobell & Sobell 1995a,
significant financial savings of $US7171 (because of 1995b), the Quick Drinking Screen (Sobell et al. 2003),
reduced motor vehicle events) per intervention patient health screening surveys or the Alcohol Use Disorder
with consecutive sustained alcohol reduction (Fleming Identification Test (AUDIT; Saunders et al. 1993). Five
et al. 2002). Further potential cost savings were studies (three RCTs, one prospective cohort study and
estimated by Magnus et al. (2012) for the Australian one case-crossover study) only relied on self-reports
society: an annually reduced alcohol intake per capita (Persson & Magnusson 1989; Longabaugh et al. 2001;
of 3.4 l resulted in decreased incidence of alcohol-related Borges et al. 2006; Gual et al. 2009; Liu et al. 2011), thus
diseases and injuries and thus in a monetary benefit of not excluding potential bias toward socially desirable
$A789million in the health-care system, $A427million answers regarding alcohol consumption. However, some
in workforce production and $A21million in home-based studies implemented beneficial features in order to
production (household duties, recreation, social and minimize limitations of self-reported measures of drinking
community leisure activities). behavior such as assessment of biomarkers (Persson &
The examined study samples varied in terms of Magnusson 1989; WHO Brief Intervention Study Group
participant’s level of baseline alcohol consumption (i.e. 1996), administration of alcohol dipsticks (WHO Brief
study inclusion cut-offs; Table 2). Whereas one RCT Intervention Study Group 1996), asking informants like
consisted of at-risk drinking individuals screened positive family members or significant others (WHO Brief
for chronically increased alcohol intake (i.e. ≥50 g Intervention Study Group 1996; Fleming et al. 1999,
ethanol per day in men and 32 g ethanol per day in 2002; Mann et al. 2005; Gual et al. 2009) or using an

‘accuracy’ contract signed by subjects (WHO Brief Inter- Effects of alcohol reduction on physical symptoms
vention Study Group 1996), respectively.
Coronary heart disease, cardiomyopathy and cardiovascular
Several methodological issues remain and may limit
diseases
the observed results: only Ronksley et al. (2011) found
no publication bias for their meta-analyzed data, whereas We identified three meta-analyses (Xin et al. 2001;
both other meta-analyses did not test for it (Di Roerecke & Rehm 2010; Ronksley et al. 2011), one open,
Castelnuovo et al. 2006; Rehm & Roerecke 2013). cross-over, randomized trial (Howes 1985); one quasi-
Fleming et al. (2002) did not report the exact alcohol experimental trail (Hsieh et al. 1995); and two longitudi-
amounts consumed at the last follow-up of 4 years. nal cohort studies (Sesso et al. 2000; Nicolás et al. 2002).
Persson & Magnusson (1989) assessed only a rather We report the RCT by Kawano et al. (1998), which was
small sample size (N = 36), and blood samples of control also included in the meta-analysis by Xin et al. (2001),
subjects were only provided by about half of the recruited because of noteworthy information on circadian differ-
sample size; further changes in alcohol intake were only ences in blood pressure changes after alcohol reduction.
assessed for the intervention group but not for the For detailed information, please see Table 2.
control group, which does not allow to conclude whether Various studies reported a linkage between light to
the significant decrease in yearly ‘sickness allowance moderate alcohol use and cardioprotective effects (Xin
days’ are truly because of alcohol reduction or if it is more et al. 2001; Ronksley et al. 2011; Sesso et al. 2000; please
of a treatment effect only seen in the intervention group also see critical review by Lieber et al. 2003). As reported
although controls diminished drinking as well (Persson in the meta-analysis by Ronksley et al. (2011), comparing
& Magnusson 1989). Again, caution has to be paid to alcohol-drinking individuals with subjects not drinking
the interpretation of results only found in individuals alcohol at all, the most beneficial effects of daily alcohol
undergoing interventions, thus not allowing to conclude intake were observed for 2.5–14.9 g ethanol (resembling
simple causal linkage between alcohol reduction and up to one alcoholic drink) resulting in 25% lowered risk
the consecutive effects observed for sickness allowance of incidences of coronary heart disease, 21% less
days (Longabaugh et al. 2001), legal problems (Fleming mortality of coronary heart disease and 23% less risk of
et al. 2002) or health-care service use (Fleming et al. cardiovascular disease (CVD) mortality. Similarly, another
2002; Liu et al. 2011), but also assuming a modifying longitudinal cohort study found that a further long-term
effect on alcohol behavior via the specific intervention reduction of an already moderate baseline alcohol
applied. consumption level (from 1–6 drinks per week or 13 to
Attention should be paid to the fact that some studies 78 g ethanol per week, respectively, down to ≤1 drink
used cross-sectional (simulation) models (Di Castelnuovo per week) does not result in significant attenuations of
et al. 2006; Rehm et al. 2011; Ronksley et al. 2011; CVD risk in men during the course of 7 years (Sesso
Magnus et al. 2012; Rehm & Roerecke 2013) in order et al. 2000). Instead, an increase in alcohol consumption
to investigate (dose–response) associations between to 1–6 drinks per week decreased the risk for CVD by 29%
alcohol consumption and lifetime alcohol-attributable and the risk for coronary heart disease by 28% in men
injuries, diseases or mortality, and accompanied with a baseline weekly intake of less than one alcoholic
economic effects. Therefore, most of these studies (also drink (Sesso et al. 2000) compared with those with no
including the studies by Gual et al. 2009 and Mann change in consumption pattern, supporting again the
et al. 2005) did not utilize data derived from clinical trial assumed cardioprotective properties of moderate alcohol
designs but instead used observational or survey data, use. However, with increasing intake, CVD mortality is
which have the major limitation of not allowing a simple assumed to follow a U-shaped or J-shaped alcohol
conclusion of causality between reduction of alcohol association (Ronksley et al. 2011). For example, as Sesso
intake and the observed consecutive benefits (although et al. (2000) reported, increased alcohol use from one
they might provide important information for future daily drink to two daily drinks was associated with an
experimental study designs). increased risk by 63% for CVD and 71% increased
Altogether, the reviewed studies showed beneficial ef- coronary heart disease risk in comparison with stable
fects of alcohol reduction for rather long-term (>1 year) alcohol consumption (Sesso et al. 2000). Additionally,
alcohol-related problems including injuries and mortality the described cardioprotective effect of regular moderate
rates and thus resulting in economic benefits in mostly alcohol consumption disappears as soon as episodes of
heavy drinkers, and less hospitalization and out-patient excessive drinking occur (Roerecke & Rehm 2010). As
treatment in abstinent alcohol-dependent patients com- found by Roerecke & Rehm (2010) in their meta-
pared with relapsing patients. No short-term effects analysis, individuals with irregular heavy-drinking epi-
(<1 year) of direct alcohol harm reduction were found in sodes of ≥60 g pure alcohol per occasion (≥12× per year
alcohol-related problems or health-care service use. but <5× per week) are prone to a 45% increased

morbidity and mortality risk for ischaemic heart disease between values in the intervention versus control groups
compared with individuals with a regular, moderate (Xin et al. 2001). This blood pressure (alcohol) reduction
alcohol use pattern, even after adjusting for study type, effect was even consistently observed within diverse
age and smoking, or separation of former drinkers to subgroups (with different sample sizes, study designs,
control for so-called sick-quitters (i.e. persons who might duration or methods of intervention, blood pressure
have quit drinking because of adverse effects of previous measurement method, with or without hypertension,
excessive alcohol use). Thus, in persons at high risk, intake of antihypertensive medication), with enhanced
alcohol reduction can therefore be an effective treatment benefit for persons with higher baseline values (Xin
method for cardiological diseases (such as alcohol- et al. 2001). The shortest changes of blood pressures were
induced cardiomyopathy; Nicolás et al. 2002) and CVD reported in another RCT: 10 normotensive subjects who
(e.g. hypertension; Xin et al. 2001). In terms of alcoholic usually drank 10–40 g ethanol per day showed raised
cardiomyopathy, a condition following chronic alcohol blood pressures after 4 days of increased intake of 80 g
misuse for years, the longitudinal cohort study over ethanol per day (systolic: mean 120 mmHg, diastolic:
4 years by Nicolás et al. (2002) found that cardiac 66 mmHg), and significantly different from that, lower
function (e.g. ventricular ejection function, cardiac blood pressures after 4 days of alcohol abstinence
contractility, end-diastolic and end-systolic diameters, (systolic: mean 112 mmHg, diastolic: 60 mmHg) (Howes
ventricular mass) can improve by 24.4% (for left ventric- 1985), demonstrating already acute alcohol (reduction)
ular ejection fraction) in patients who abstained effects. In order to understand the cellular and biochem-
completely from alcohol, but also in patients who ical mechanism behind this well-described positive associ-
reduced their drinking from formerly >100 g ethanol ation between alcohol intake and blood pressure, a
per day down to a maximum of 20–60 g pure alcohol Japanese study (Hsieh et al. 1995) was conducted in 17
per day by about 8.7% for left ventricular ejection mild-hypertensive patients, who reduced their regular
fraction; this was seen in comparison with patients who alcohol use from of 461.7 g per week—consumed for
remained stable harmful drinkers. Deterioration of the last ≥10 years—to 71.6 g per week, compared with
cardiac function was observed in patients who remained 12 non-alcohol drinking, mild-hypertensive controls.
drinking more than 60 g ethanol per day (and especially While a significant correlation between the observed,
in those with >80 g ethanol per day). Concerning death decreased mean and systolic blood pressure and the
rate of cardiac disease during the follow-up period, no 4-week alcohol limitation was found, the authors also re-
one of the abstinent or reduced drinking patients died, ported significantly augmented (thus normalized) serum
but 41% total cardiac mortality occurred in those who and intra-erythrocyte magnesium concentrations as well
drank more than 80 g ethanol per day (Nicolás et al. as increases in Kos (a marker of erythrocyte sodium pump
2002). activity) along with the reduced alcohol use. On the
Because chronic alcohol use could also lead to arterial other hand, significantly attenuated intra-erythrocyte
hypertension (i.e. systolic BP ≥140 mmHg, diastolic sodium concentrations were shown under alcohol
BP ≥ 90 mmHg; Appel et al. 2006; Whelton et al. 2002), restriction among other unchanged biochemical parame-
which can induce heart attacks, strokes or kidney dam- ters (Hsieh et al. 1995; Table S1). Furthermore, Hsieh
ages (Xin et al. 2001; Whelton et al. 2002; Mundle et al. (1995) revealed different associations between the
et al. 2003; Appel et al. 2006; Ronksley et al. 2011), the elevated intra-erythrocyte magnesium concentration
quantity of individual alcohol consumption represents and (1) the fall of mean blood pressure or (2) the raised
one of the most important modifiable risk factors of high sodium pump activity (Kos), which in turn was related
blood pressure (Xin et al. 2001; see also review by Cush- to diminished intra-erythrocyte sodium concentration.
man 2001). In a meta-analysis of 15 randomized Based on these findings, Hsieh and colleagues assumed
controlled trials, data of 2,234 normotensive and hyper- that the recovery of a cellular magnesium deficiency
tensive participants were analyzed to evaluate the effects contributes to the reduced alcohol intake and reduced
of alcohol reduction on blood pressure for the first time blood pressure effect by mechanisms such as an increased
(Xin et al. 2001). Here, the authors found a positive sodium pump activation combined with a decreased
dose–response relationship such as a reduction of daily intracellular sodium concentration (Hsieh et al. 1995).
alcohol intake by 67% in ‘fairly heavy drinkers’, who con- Also noteworthy, another RCT pointed out circadian
sumed, prior to intervention, 3–6 daily alcoholic drinks differences in blood pressure changes accompanied with
with 12 g ethanol, resulting in a highly significant decre- 4 weeks of alcohol limitation in hypertensive Japanese
ment of systolic and diastolic blood pressure. An average ‘habitual drinkers’ (24 g ethanol per day or more): while
net change of systolic 3.31 mmHg (millimeter of mer- daytime systolic and diastolic blood pressure (6:30 AM
cury) and diastolic 2.04 mmHg was detected either to 9:00 PM) were reduced under alcohol restriction from
between baseline and follow-up measurements or 52.8 g to 8.8 g ethanol per day, both blood pressures

20
Table 3 Summary of the characteristics of 4 studies included for investigation of the effects of alcohol reduction on physical and mental measures in adolescents and young adults.
Study Sample
Study Study design Total follow-up period Age (years) (inclusion criteria for alcohol use, if given) Alcohol use measures Outcome measures
Newton Cluster 6 months Mean (SD) only: N = 764 Frequency of consumption Alcohol knowledge,
et al. RCT 13.08 (0.58) over the past 3 months, Alcohol-related harm
2009 Quantity of consumption in (experienced from own use),
standard drinks over the past Alcohol-related expectancies
3 months,
Frequency of consuming

above low-risk levels for
occasional
consumptiona in the past
3 months
Kypri RCT 6 months 17–24 N = 13,000 Frequency of drinking, Alcohol problems (personal,
et al. (AUDIT score ≥8 and binge Number of standard drinks social, sexual, legal and academic
2009 drinkingb within the previous per typical problems)
4 weeks) drinking occasion,
Weekly alcohol consumption,
Prevalence of binge drinking
and heavy drinkingb
Vogl Cluster- 12 months Mean N = 1434 Frequency of weekly alcohol Alcohol knowledge,
et al. RCT (SD) only: consumption over the past Alcohol-related harm
2009 13 (0.40) 3 months, (experienced from own use),
Weekly quantity of consumption Alcohol-related expectancies
per occasion over the past
3 months,
Frequency of consuming
in excess of the low-risk levels
for occasional consumption
over the past 3 monthsa
McBride Quasi- 32 months 13–14 N = 2300 Frequency of consumption, Alcohol knowledge,
et al. experimental Amount of alcohol consumed Attitudes toward alcohol,
2004 trial per occasion, Context of alcohol use,
Total amount of alcohol over Harm/risk associated with the
12 months, student’s own alcohol consumption,
Amount and frequency Harm/risk associated with other
of harmful/hazardous people’s alcohol consumption
Addiction Biology
RCT = randomized controlled trial. aAccording to the Australian Alcohol Guidelines for adults: women ≥4 standard drinks of 10 g pure alcohol [per occasion], men ≥6 standard drinks of 10 g pure alcohol [per occasion]. bAccording to
Australian National Health and Medical Research Council’s guideline (cf., Kypri et al. 2009): women >4 standard drinks of 10 g pure alcohol on one occasion in the preceding 4 weeks, men ≥6 standard drinks of 10 g pure alcohol on
increased significantly throughout the nighttime (9:30
PM to 6 AM), but without consequences regarding the
quality of sleep (Kawano et al. 1998). While 24-hour
total blood pressure did not differ between pre-
intervention and post-intervention, heart rates during
Outcome measures
the day and night as well as 24-hour heart rate did
decrease altogether after alcohol reduction. Thus, the 4-
week limited alcohol intake diminished the mean day–
night blood pressure difference, but longer alcohol reduc-
tion might be needed in order to lower sustainably the
average 24-hour blood pressures, according to the
investigators (Kawano et al. 1998). Thus, besides
reducing the quantity of drinking, the duration of alcohol
ETOH per occasion, men:
40 g ETOH per occasion)
restriction also appears to be relevant: a long-term

drinking (women: 20 g
Alcohol use measures
instead of a temporary alcohol reduction is

recommended, because blood pressures rise again when
alcohol intake increases (Kawano et al. 1998).
In regard of the methodological issues, major limita-
tions of the reviewed studies were the correlational na-
ture of the meta-analyses based on observational studies
(Roerecke & Rehm 2010; Ronksley et al. 2011), which
limits causational conclusions. However, the meta-
(inclusion criteria for alcohol use, if
analysis of Xin et al. (2001) was based on RCTs testing

the effect of restricted alcohol consumption on blood
pressure and indicates a consecutive, protective effect
Study Sample
on cardiovascular disease such as hypertension. Further-

given)
more, although the meta-analyses did not find any publi-

cation bias in their investigations (Xin et al. 2001;
Roerecke & Rehm 2010; Ronksley et al. 2011), one
should keep in mind that other biases may also be intro-
duced by the fact that the reported findings always de-
pend on the quality of the included studies, especially in
terms of study power, follow-up constraints or variation
in adjustments for potential confounding variables (Xin
Age (years)
et al. 2001; Roerecke & Rehm 2010; Ronksley et al.

2011). Here, one further potential bias is that of self-
reported measures of alcohol intake. The included studies
either assessed drinking behavior via structured ques-
tionnaires (Kawano et al. 1998; Nicolás et al. 2002) or
other self-reported measures (Sesso et al. 2000), with
Total follow-up
only one study providing validation of self-reports by fam-

ily members (Nicolás et al. 2002). Exact information on
period
the method of alcohol assessment was lacking for three

studies (Howes 1985; Roerecke & Rehm 2010; Ronksley
et al. 2011). RCTs included in the meta-analysis by Xin
one occasion in the preceding 4 weeks.
et al. (2001) used self-reported alcohol measures, but no

further details were given. Regarding the study samples,
Study design
one study (Nicolás et al. 2002) investigated the effects of

alcohol reduction on cardiological or cardiovascular dis-

eases in alcohol-dependent patients, whereas three trials
studied alcohol-drinking individuals without a diagnose
for alcohol use disorder (Howes 1985; Kawano et al.
Study
1998; Sesso et al. 2000). Also, special cohorts such as

physicians were observed, which might not be

representative to the general population or the general triglyceride level (TG) (Cox et al. 1993), high-density lipopro-
cohort of patients we see in clinical treatment (Sesso tein cholesterol (HDL-C) (Puddey et al. 1985; Parker et al.
et al. 2000). Further information on inclusion of 1990; Ueshima et al. 1993; Hsieh et al. 1995; Kawano
alcohol-dependent patients, or whether it was tested for et al. 1998) with specific reductions of HDL, HDL2 and
alcohol use disorder, respectively, was missed in four HDL3 cholesterol (Cox et al. 1993), and significant weight
studies (Hsieh et al. 1995; Xin et al. 2001; Roerecke & loss of 0.7 kg in 4–-14 weeks (Puddey et al. 1985; also in
Rehm 2010; Ronksley et al. 2011). Also, studies using Hsieh et al. 1995); for biometric details, see Table S1.
small sample sizes of 10–34 participants (with further Here, particularly subjects with high baseline serum-γ-
group separation into smaller subgroups) limit reliance GT levels showed beneficial blood pressure effects follow-
on study results (Howes 1985; Hsieh et al. 1995; Kawano ing alcohol reduction by 10%, accompanied with a
et al. 1998). normalization of this hepatic enzyme as well as of (high
The reviewed studies show that, on one hand, stable baseline) lipids and electrolytes (serum AST, thrombozytic
moderate alcohol intake may provide cardioprotective ef- free calcium, sodium, potassium and TG level) were found
fects, and on the other hand, particularly individuals at (Yamada et al. 1997; Table 2 and S1).
high risk (e.g. subjects with irregular heavy alcohol use, After 18 weeks of alcohol restriction, significant atten-
hypertensive persons or patients with cardiomyopathy) uations of total cholesterol concentration, TG, γ-GT and
may benefit from sustained alcohol reduction as an effec- HDL-C as well as an average further weight reduction of
tive (pre-)intervention method for lowering disease risk or 2.1 kg were reported (Puddey et al. 1992); Table S1.
even improving heart function (e.g. Xin et al. 2001; Long-term parameter differences after 12 months of self-
Nicolás et al. 2002; Whelton et al. 2002; Appel et al. reported alcohol reduction were also found for dimin-
2006). Here, cardiological experts further recommend ished γ-GT, but only in male (not female) excessive
for the prevention of hypertension (and for individuals drinkers; no changes were seen in aspartate transaminase
with already existing hypertension) not to exceed drink- or mean cell volume (Wallace et al. 1988). Another RCT
ing of 1–2 alcoholic beverages per day (i.e. 12–24 g etha- on alcohol moderation (but not in relation to blood pres-
nol per day) (Whelton et al. 2002; Appel et al. 2006). sure changes) found alternatively significant decreases in
serum biomarkers (i.e. mean γ-GT by 34% or 0.32 μkat/l
γ-GT, respectively, and TG by 24% or 0.52 mmol/l, respec-
Effects on biochemical parameters
tively), accompanied with reduced alcohol intake by 29–
Particular biomarker parameter effects following alcohol 35% (from average weekly 164–179 g ethanol to 117 g
moderation (and accompanying blood pressure changes) ethanol/week) over 12 months of observation in a sample
were provided by 11 RCTs (Puddey et al. 1985, 1992; of both female and male problem drinkers (Persson &
Wallace, Cutler, & Haines 1988; Parker et al. 1990; Magnusson 1989). Contrary, two further long-term RCTs
Maheswaran et al. 1992; Cox et al. 1993; Ueshima et al. did not find any significant decreases in γ-GT or mean red
1993; Lang et al. 1995; Cushman et al. 1998; Kawano cell corpuscular volume together with significantly reduced
et al. 1998; Rakic et al. 1998). These RCTs were all in- alcohol intake by 17% or 43% over the course of
cluded in the previous mentioned meta-analysis by Xin 12 months in heavy-drinking men with initial average
et al. (2001), but are reviewed in this section in detail be- intake of 525 g ethanol per week (Anderson & Scott
cause valuable information is provided regarding bio- 1992) or in heavy-drinking women, respectively, with
marker changes; please see also Table S1. Additionally, an initial average intake of 364 g ethanol per week (Scott
biochemical investigations were reported in three RCTs & Anderson 1991). In turn, longer investigations beyond
(Persson & Magnusson 1989; Scott & Anderson 1991; 12 months of observation either did find beneficial
Anderson & Scott 1992), one quasi-experimental trail biochemical developments together with decreased
(Hsieh et al. 1995) and two prospective cohort studies alcohol use (Cushman et al. 1998), or found no changes
(Yamada et al. 1997; Balkau et al. 2006); for study in biomarkers such as γ-GT, if alcohol intake was not
details, see also Table 2. successfully reduced (Lang et al. 1995). Here, the RCT
Together with the lowering of blood pressures, short- by Cushman et al. with a follow-up period of 24 months
term changes after 3–14 weeks of limited alcohol use reported that a sustained 50% cut down of the individual
have been reported for lowered γ-glutamyltranspeptidase non-addicted, moderate to heavy alcohol use lead to
(γ-GT; also γ-glutamyltransferase) (Puddey et al. 1985; significant decreases in HDL-C, HDL3, apolipoprotein A1
Maheswaran et al. 1992; Ueshima et al. 1993; Hsieh and A2, and γ-GT in men as well in women (Cushman
et al. 1995; Kawano et al. 1998; Rakic et al. 1998), apoli- et al. 1998; Table S1). A longitudinal cohort study
poprotein A1 and A2 (Parker et al. 1990; Cox et al. 1993), followed metabolic syndrome parameters due to alcohol
aspartate aminotransferase (AST) (Maheswaran et al. moderation among other changes in lifestyle habits over
1992), mean corpuscular volume (Puddey et al. 1985), a period of 3 years (Balkau et al. 2006). Of the 3305

alcohol drinkers, 25% of men and 13% of women participants’ alcohol intake by self-reports only without
decreased their consumption by at least 2 g/day, but only any corroborative evidence by significant others, thus tol-
in men this reduction was associated with significant ef- erating the potential of socially desirable reporting bias
fects on systolic blood pressure and HDL-C (Balkau et al. (Puddey et al. 1985, 1992; Wallace et al. 1988; Persson
2006; Table S1). The authors found that ‘for a 10 g de- & Magnusson 1989; Parker et al. 1990; Scott & Anderson
crease in pure alcohol intake or one glass of wine, HDL- 1991; Anderson & Scott 1992; Maheswaran et al. 1992;
C decreased by 0.01 mmol/l on average and systolic blood Cox et al. 1993; Ueshima et al. 1993; Hsieh et al. 1995;
pressure by 0.29 mmHg’ (Balkau et al. 2006; p. 338). Lang et al. 1995; Yamada et al. 1997; Cushman et al.
As in most of these RCTs shown, the more the individ- 1998; Kawano et al. 1998; Rakic et al. 1998). The
ual alcohol intake was reduced, the greater average bio- remaining 17th study by Balkau et al. (2006) even lacked
chemical changes were observed (e.g. Parker et al. completely to report how alcohol consumption was
1990; Cushman et al. 1998). However, the reported de- assessed. Other methodological caveats have to be taken
crease in HDL-C following alcohol reduction should be into account when interpreting the results: most studies
treated with caution, because HDL-C functions as a conducted only small sample sizes of 29–41 individuals
cardioprotective cholesterol efflux from macrophages (which were again separated), thus limiting the power
(Cox et al. 1993; Heinecke 2013). According to the ex- of the investigated effects (Maheswaran et al. 1992; Hsieh
pert panels like the American Heart Association or the Na- et al. 1995; Yamada et al. 1997; Kawano et al. 1998).
tional Cholesterol Education Program, an HDL-C level of Lang et al. (1995) lacked a precise description of e.g. data
≥40 or 50 mg/dl is recommended, whereas a lower level assessment or results. And Wallace et al. (1988) concede
is considered as one of the major risk factors for athero- that their participants’ motivation level might have po-
sclerosis, CVD, heart disease or stroke (Toth 2005). A so- tentially moderated the observed dose–response effects,
phisticated reflection on the HDL-C, which is mostly because of the shown proportional link between the alco-
assessed as a surrogate marker for HDL concentration, hol reduction effect and the frequency of subjects attend-
is provided by Lieber (2003) and Heinecke (2013). The ing to intervention sessions. Noteworthy, the vast
latter remarks that HDL-C does not necessarily reflect majority of reviewed studies reported subsequent changes
cardioprotective traits of HDLs, and instead (level-inde- of biochemical parameters after previous alcohol restric-
pendent), specific HDL proteins were associated with in- tion, only except for three RCTs (Scott & Anderson
creased and others with decreased risk of cardiovascular 1991; Anderson & Scott 1992; Lang et al. 1995). None-
diseases (Heinecke 2013). These observations caution theless, concomitant lifestyle changes during the study
not to recommend moderate alcohol intake in order to periods could partly explain these effects as well. How-
raise general HDL levels. ever, nine RCTs found no significant lifestyle changes dur-
Most of these reviewed studies investigated biochemi- ing their studies—which rather supports the
cal changes along with alcohol restriction regimes, but interpretation that bio-parameters changed because of
only five of them gave concrete information about their alcohol reduction (Puddey et al. 1985; Wallace et al.
sample subjects who were normotensive or hypertensive 1988; Parker et al. 1990; Scott & Anderson 1991;
individuals without any diagnose of alcohol use disorder Anderson & Scott 1992; Maheswaran et al. 1992; Cox
(Persson & Magnusson 1989; Maheswaran et al. 1992; et al. 1993; Cushman et al. 1998; Rakic et al. 1998). Five
Yamada et al. 1997; Cushman et al. 1998; Kawano studies did not assess explicitly possible concomitant life-
et al. 1998). The remaining 12 studies missed to provide style modifications (Persson & Magnusson 1989;
further information on whether alcohol-dependent pa- Ueshima et al. 1993; Lang et al. 1995; Yamada et al.
tients were included, or if participants were tested for 1997; Kawano et al. 1998). And only three studies did
the diagnose of alcohol use disorder, respectively (Puddey find also beneficial associations between sporting, physi-
et al. 1985, 1992; Wallace et al. 1988; Parker et al. 1990; cal activity, body weight or body mass index change
Scott & Anderson 1991; Anderson & Scott 1992; Cox and biochemical (metabolic syndrome) parameters in ad-
et al. 1993; Ueshima et al. 1993; Hsieh et al. 1995; Lang dition to the alcohol-related biomarker associations
et al. 1995; Rakic et al. 1998; Balkau et al. 2006). Fur- (Puddey et al. 1992; Hsieh et al. 1995; Balkau et al.
thermore, 13 of the reviewed studies either assessed 2006); please see also Tables 2 and S1.
drinking behavior via structured questionnaires or stan-
dardized drinking diaries (Puddey et al. 1985, 1992;
Oncological effects
Wallace et al. 1988; Parker et al. 1990; Scott & Anderson
1991; Anderson & Scott 1992; Maheswaran et al. 1992; To the best of our knowledge, no clinical trials examined
Cox et al. 1993; Hsieh et al. 1995; Yamada et al. 1997; yet whether distinct alcohol reduction results in
Cushman et al. 1998; Kawano et al. 1998; Rakic et al. decreased risk of (pre)cancer. However, there are findings
1998). Sixteen out of the 17 investigations assessed strongly supporting the assumption of a direct dose–

response dependence of alcohol intake and cancer risk. breast cancer. Particularly, this cancer risk increased by
Therefore, we report one case-control study, which was an average of 9% per additional, daily consumed 10 g
found to investigate the association between alcohol con- alcohol up to 60 g/day (Smith-Warner et al. 1998). This
sumption and the risk of esophageal cancer (Hanaoka finding is in line with an earlier meta-analysis of 38
et al. 1994), whereas further two studies, one meta- epidemiological studies conducted by Longnecker
analysis (Longnecker 1994) and one pooled analysis (1994), who reported an increased relative breast cancer
(Smith-Warner et al. 1998), specifically examined the as- risk in women by about 11–13% with each additional
sociation of alcohol dose and the risk of suffering from drink of 13 g pure alcohol daily, up to a 38% increased
breast cancer (cf., Table 2). relative cancer risk when consuming three drinks or
Following The Association of the Scientific Medical 39 g ETOH per day, respectively. According to both studies
Societies in Germany, increased chronic alcohol consump- other factors (like menopausal status, maternal and fe-
tion is a major risk factor (besides chronic tobacco use) male sibling history of breast cancer, hormonal
for the development of carcinoma of the oral cavity with therapy/contraceptives, body mass index, socioeconomic
an evidence level of 2++. Worldwide, annually increas- status and age at first birth) did not influence this
ing incidence rates of 200,000 to 350,000 new cases oc- observed association, which indicates that this increasing
cur. Individuals with high chronic alcohol intake show a cancer risk by increasing alcohol use applies to the
sixfold increased risk of this disease, particularly men majority of women (Longnecker 1994; Smith-Warner
aged between 55 and 65 years (AWMF German Guideline et al. 1998). As causal mechanisms of this increased
Program in Oncology, Guideline Oral Cavity Carcinoma, cancer risk, alcohol-associated increased estrogen level
state 12.2012). Also, the International Agency for Research in women and co-carcinogenic effects of alcohol are
on Cancer (IARC 2010) states sufficiently evidenced carci- hypothesized (e.g. Smith-Warner et al. 1998).
nogenicity of alcoholic beverages in humans as follows: When it comes to cancer, one has also to consider the
‘The occurrence of malignant tumors of the oral cavity, carcinogenic effects of common comorbid tobacco
pharynx, larynx, esophagus, liver, colorectum and female smoking (see previous sections). Therefore, statistical
breast is causally related to the consumption of alcoholic accounting for these smoking effects as seen in the anal-
beverages. [However,] there is evidence suggesting lack of yses by Hanaoka et al. (1994) can display one possible
carcinogenicity in humans for alcoholic beverages and way of methodologically addressing this important issue.
cancer of the kidney and non-Hodgkin lymphoma’ (IARC Interestingly, they found that tobacco consumption—
2010, p. 1278). Thus, besides general education, one of when odds ratios were adjusted for weekly consumed
the primary actions to prevent cancer should be consul- alcohol amount—was no longer significantly associated
tancy and help in reducing excessive alcohol use at least with heightened esophageal cancer risk, which indicated
in high-risk populations (e.g. Longnecker 1994; that this cancer type is rather alcohol attributable
Smith-Warner et al. 1998). We found one case-control (Hanaoka et al. 1994). Also, Smith-Warner et al. (1998)
study that supports the assumption of carcinogenic found no significant interacting effect of smoking on the
effects of excessive alcohol use indicated by a direct link positive association of alcohol intake and breast cancer
between the risk of esophageal cancer compared with risk, whereas Longnecker (1994) did not address this
other cancer types and the amount and frequency of potential modifier in his analyses.
consumed alcohol (Hanaoka et al. 1994). Here, quanti- Nonetheless, there are major limitations of the
ties of ≥242 g ETOH per week were related to significant reviewed studies in this section. For example, the case-
fivefolded to sixfolded increases in esophageal cancer risk control study by Hanaoka et al. (1994) only provides cor-
compared with ≤53 g ETOH per week, whereas frequen- relational conclusions in a population newly diagnosed
cies of alcohol intake of more than three times per week with primary esophageal cancer (‘cases’) or other cancer
were accompanied by a threefold to sevenfold increase types or chronic pancreatitis (‘controls’), respectively,
in esophageal cancer risk both in Japanese inpatients drawn from surgical wards of multiple hospitals without
compared with their non-drinking, matched counter- detailed description of possible alcohol problems in the
parts (Hanaoka et al. 1994). past, which also applies for the non-drinking control
Concerning breast cancer, an international pooled group. While frequency and amount of alcohol use were
analysis by Smith-Warner et al. (1998), including six pro- gained via ‘structured questionnaires’ (not described in
spective cohort studies with a total of 322,647 women detail), no verification by patients’ collaterals were gath-
followed for a total of 11 years found a linear dose– ered. Further in this study, Hanaoka et al. (1994) discov-
response relationship between the consumed alcohol ered also that ‘preference for high-temperature food and
amount and the risk of invasive breast cancer. Compared drink’ as another lifestyle factor was associated with an
with non-drinkers, an alcohol intake of 30–60 g/day was increased esophageal cancer risk, but only after adjust-
associated with a 41% higher relative risk of invasive ment for patients’ weekly alcohol intake. Now, questions

remain whether variables of alcohol intake (quantity and diseases (a state that is assumed to be potentially revers-
frequency) would have yielded significant relations to this ible). For both patient groups (those who abstained and
cancer risk, too, if accounted for patients’ dietary prefer- those who reduced significantly their alcohol intake from
ence for high temperatures? Moreover, both pooled and 3.52 g to 1.2 g/kg body weight over the 12 week observa-
meta-analyses on alcohol use and female breast cancer tion period), overall histological improvements were
risk did in part rely on three of the same original follow- similar, independent of whether patients received
up studies (Willett et al. 1987; Gapstur et al. 1992; catechin or placebo. Of the 41% of total abstainers,
Friedenreich et al. 1993), which may have influenced 62.5% displayed improved liver histology and of the
their overall results (Longnecker 1994; Smith-Warner 51% of patients who reduced their alcohol intake by
et al. 1998). Additionally, strong variations in the original 69.5% showed beneficial histological changes. Further,
study results were reported, but could only be partially abstainers showed improved biochemical parameters
explained by the modification effects of different per capita (i.e. in mean AST and γ-GTP), and both abstainers and
consumption levels, different follow-up lengths or impre- reduced drinkers additionally showed lowering of mean
cise self-reports of alcohol consumption (Longnecker MCV (Colman et al. 1980). That is why Colman et al.
1994). Also, both meta-analytic investigations incorpo- (1980) conclude that most striking effects of liver
rated data with heterogeneity of women regarding their recovery are due to significant alcohol reduction with (if
breast cancer risk in the studies (e.g. due to estrogen only) negligible catechin effects.
replacement therapy or genetic risk load) or women’s Another longitudinal, randomized, placebo-
current and former alcohol use, respectively, with no controlled trial also observed that the progression of
further information given whether or not individuals an already existing alcohol-induced liver fibrosis was
with a diagnosed alcohol dependence or so-called sick- slowed down and even reversed over 2 years by reduc-
quitters were included (Longnecker 1994; Smith-Warner ing the average alcohol consumption of previously
et al. 1998). 224 g to 35 g ETOH per day in 56% of the heavy-
Specific attention has to be paid to the fact that the drinking study sample—independently of whether the
included studies in this section can only allow interpreta- patients perceived any other treatment than alcohol re-
tions on the basis of associative relationships instead of duction; however, this did not abolish liver fibrosis
direct causal links between alcohol reduction and follow- completely (Lieber et al. 2003). While the authors as-
ing effects concerning the incidence, prevalence, progres- sumed an accelerated progression rate of 30% over
sion or mortality from cancer. Nonetheless, the observed 24 months when patients would continue to drink as
findings and the previous mentioned statements of the usual, surprisingly, under reduced drinking conditions,
AWMF and the IARC all point to evident dose–response only 20% of patients showed histological changes to-
associations between alcohol intake and increased risk ward more severe disease stages, and 20% of the pa-
for specific cancer types like esophageal or breast cancer, tients even displayed disease regression (Lieber et al.
which have to be taken into account in terms of potential 2003). Noteworthy in this context, drinking at any con-
health benefits subsequent of alcohol reduction. sumption level (i.e. even lowering to moderate alcohol
use) did not change the doubled disease progression in
patients positive for hepatitis C-virus compared with
Hepatological effects
non-infected individuals (31.5% versus 16.5%) (Lieber
We identified two randomized controlled trials investigat- et al. 2003). Therefore, the clinical practical guidelines
ing alcohol-attributable liver disease in excessively of the European Association for the Study of the Liver state
drinking individuals (Colman et al. 1980; Lieber et al. that total alcohol abstinence is ‘the most effective rec-
2003) (Table 2). ommendation’ (p. 403) in people with alcoholic liver
Because the most common alcohol-attributable cause disease in order to reduce the risk of complications
of death is cirrhosis of the liver—causing 50.2% of all and mortality (Recommendation A1; Mathurin et al.
premature deaths in Germany because of chronic alcohol 2012).
misuse (Rehm et al. 2011) and epidemiological observa- Both RCTs examined patients who self-reported (with-
tions reporting increases of liver cirrhosis risk at a daily out further verification by collaterals) to drink excessively
alcohol usage of 20–40 g ETOH (cf., Fleming et al. prior to study inclusion and thus developed alcohol-
2002), reducing the consumed alcohol amount could attributable liver damages. Although not literally ad-
result in beneficial hepatological changes. dressed, drinking extensively despite negative conse-
An early clinical trial by Colman et al. (1980) followed quences represents a characteristic of an existing
patients with a chronic alcohol intake of >80 g/day un- alcohol dependence according to ICD-10 (Dilling,
der catechin or placebo treatment in order to investigate Mombour, & Schmidt 2000), thus assuming that these
changes of their pre-cirrhotic alcohol-related liver study findings may be of special importance in terms of

evaluating potential benefits of lowering alcohol reduction was seen in light to moderate alcohol
consumption in the group of alcohol-dependent patients. consumers (6–48 g/day) (Koppes et al. 2005).
Of note, both RCTs followed a prospective design using Concerning methodological evaluation of the studies,
pharmacological substances (catechin or both studies based on (even longitudinal) observations
polyenylphosphatidylcholine) versus placebo among the cannot determine causal relationships between changes
intervention of alcohol reduction in order to test their in alcohol use and type 2 diabetes risk, but may indicate
effects on liver damage progression. However, both directional assumptions for further long-term interven-
studies did not find any significant effects caused by the tion studies. Self-reported alcohol consumption via a
substances, but instead patients who reduced their standardized questionnaire was used (Joosten et al.
alcohol intake showed significant beneficial effects— 2011). Instead of validation by others, reports were
namely, slowed progression of disease stages and cross-validated by comparison with detailed dietary
histopathological improvements. records of a sub-cohort, verifying high correspondence
(Joosten et al. 2011). Further, although reasons of chang-
ing alcohol behavior remained unclear in both studies
Diabetes
(Koppes et al. 2005; Joosten et al. 2011), additional anal-
One meta-analysis (Koppes et al. 2005) and additionally yses without baseline non-drinkers were used to mini-
one longitudinal cohort study (Joosten et al. 2011) were mize the potential bias of alcohol abstinence due to poor
found to be of relevance regarding the alcohol-associated health (but not in Koppes et al. 2005) and also adjust-
Type 2 Diabetes risk (Table 2). ments for persons’ health and lifestyle characteristics
Although alcohol use is assumed to have detrimental provided similar findings (Koppes et al. 2005; Joosten
effects on diabetes self care (e.g. forget to inject insulin et al. 2011). Also in their meta-analysis, Koppes et al.
or to monitor the blood glucose level), hypoglycemia (2005) tested ideally for various bias potentials in com-
and ketoacidosis in individuals suffering from type 1 paring multivariate-adjusted and crude relative risks,
diabetes (Barnard et al. 2012), no study was found to pooled gender-specific relative risks and pooled relative
investigate the impact of alcohol reduction or cessation risks for different body mass index strata. Additional fun-
on type 1 diabetes. nel plots assured no publication bias (Koppes et al. 2005).
Regarding type 2 diabetes, a recent longitudinal study Nonetheless, quality constraints of the included original
by Joosten et al. (2011) showed a beneficial effect of studies still influence the overall quality of the meta-
moderate alcohol use on (decreased) morbidity risk over analysis (Koppes et al. 2005). For example, Koppes et al.
a 4-year observation period, which may result from the (2005) only assume but not describe in detail differences
(also observed) alcohol-driven increases of adiponectin in alcohol assessment methods to be one among other
and decreases of Hemoglobin A1c, which in turn potential factors causing the observed heterogeneity and
improves insulin sensitivity. In detail, the study sample measurement errors of risk estimates across the included
of 38,031 male participants showed that hazard ratios studies. Also, both studies did not give information about
of men with sustained moderate alcohol consumption the inclusion of diagnosed alcohol-dependent individuals
(5.0–29.9 g alcohol per day) or an increased intake from in their populations (Koppes et al. 2005; Joosten et al.
light to moderate alcohol levels over 4 years, respectively, 2011). While Joosten et al. (2011) examined a male only
displayed a 25–26% lower type 2 diabetes risk compared cohort of US health professionals who may represent a
with stable light drinkers (0–4.9 g alcohol per day). No particular health-educated population and thus impacts
differences in morbidity risk were seen between these their lifestyle including a more conscious alcohol use,
stable light drinkers and moderate drinkers who reduced findings of the study by Koppes et al. (2005)—which
their alcohol consumption down to light or none support Joosten’s results—may promote the generaliz-
drinking, respectively, over the 4 years study period ability of those observed associations between lowered
(Joosten et al. 2011). Also, already moderately drinking diabetes type 2 risk and moderate alcohol intake.
individuals did not further benefit from increased alcohol
use in terms of type 2 diabetes risk (Joosten et al. 2011).
Tuberculosis
In line, a previous meta-analysis of 15 prospective
cohort studies (12 years average follow-up period) We identified one systematic review that additionally
revealed that (independently of the gender, body mass analyzed pooled effect sizes of their included cohort and
index and physical activity) the amount of consumed case-control studies (Lönnroth et al. 2008) (Table 2).
alcohol and type 2 diabetes risk were associated in a While international investigations show a strong asso-
U-shaped relationship (Koppes et al. 2005). Whereas ciation between high exposure to alcohol use and the
non-drinkers and drinkers above the level of 48 g ETOH tuberculosis risk, Lönnroth et al. (2008) support this by
per day was similar, a highly significant 30% risk showing a significant threefold increased relative risk

(pooled odds ratio) for active tuberculosis to be related to displayed an 8% lower pooled relative risk for incidences
consumption of more than 40 g alcohol per day, and to of ischaemic stroke and a higher relative risk for the
alcohol use disorder (whereas no information was incidence of a hemorrhagic stroke by 14% (Ronksley
provided by the single studies regarding how alcohol et al. 2011). While the authors conclude, that daily
use disorder was diagnosed; cf., Lönnroth et al. 2008). alcohol intake of 2.5–14.9 g ethanol has ‘protective’
In contrast, low to moderate alcohol use (<40 g ETOH properties in regard of stroke incidence density ratios
per day) was not significantly associated with increased and mortality hazard ratios (as well as for previously
tuberculosis risk. Controlling for potential confounding mentioned coronary heart disease and cardiovascular
variables such as age, sex, HIV, smoking or socioeco- disease), consumption of more than 60 g ethanol per
nomic status did not change these findings. Among day was associated with a significantly increased relative
others, the authors discuss that one explanation for the risk of incident stroke by 62% compared with no alcohol
increased risk of infection could be found in ‘[alcohol-] (Ronksley et al. 2011). While on the upside—again in
specific social mixing patterns’, often accompanied by terms of methodological evaluation—this meta-analysis
‘social downward drift’ [Lönnroth et al. 2008; p.10]. This could rule out any publication bias by the included orig-
suggests that individuals with alcohol use disorder are inal studies, final data validity still contains single study
often found in e.g. bars, social service institutions and limitations, e.g. heterogeneity in confound adjustments
prisons—places with high exposure and transmission or potential misclassification of alcohol use caused by
rates of tuberculosis (Lönnroth et al. 2008). Furthermore, individuals’ underreporting, where detailed information
high exposure to alcohol may have detrimental effects on on methods of alcohol assessment within studies were
the immune system, in a way of accelerating infections to not described. Also, because this meta-analysis does not
full disease stage, which was supported by an observed provide any information whether or not alcohol-
pooled odds ratio of 4.2 (Lönnroth et al. 2008). Of note, dependent patients were included in the reviewed cohort
these findings are based on categorical alcohol consump- studies, one might be cautious in generalizing and
tion level analyses with groupings of studies for ‘low promoting beneficial effects of moderate consumption
exposure’ (alcohol intake <40 g/day) and ‘high exposure’ regarding stroke incidence and mortality in the high-risk
(alcohol intake >40 g/day, including ‘ascertained diagno- group of alcohol-dependent patients.
sis of alcohol use disorder’), which does not allow to Overall, these findings indicate that lowering of risky
conclude a linear dose–response relationship between and harmful alcohol use (cf., Table 1) may potentially
dimensional alcohol use and tuberculosis risk (Lönnroth prevent cerebral hemorrhage and ischaemic stroke or at
et al. 2008). Further, there was a high degree of heteroge- least lead to a decrease of individual stroke risk; however,
neity of the original studies observed, which could be the exact population subgroups where this applies to best
partly explained by possible errors in classification of must still be clarified.
individuals’ alcohol exposure. Because of insufficient
information in the original reviewed investigations, this
Effects of alcohol reduction on mental health and quality
could not be addressed adequately (Lönnroth et al.
of life
2008). Another potential underestimation of odds ratios
could be due to selection of higher consuming controls Within this topic, we identified two RCTs (Potamianos
(such as prisoners or hospital controls) as compared with et al. 1986; Heather et al. 1987) and three prospective
the general population (Lönnroth et al. 2008). Because cohort studies (Shaw et al. 1998; Hulse & Tait 2003;
funnel plots indicated publication bias by small-sampled Craig et al. 2011), which all examined alcohol reduction
studies, those three ‘high-exposure’ studies (displaying effects in patients with alcohol use disorders (Table 2).
the highest standard errors) were excluded in additional Both RCTs found beneficial effects accompanied with
analyses and resulted in a lower pooled effect size (pooled previous 17–47% alcohol reduction over the course of
odds ratio of 2.9 versus previously 3.5), but did not 6 months (Heather et al. 1987) and 1 year (Potamianos
change the observed nature of significant association et al. 1986). While a reduction of last month’s alcohol
between increased tuberculosis risk and high alcohol consumption from mean baseline intake of 1555.2 g
intake. ETOH per month to follow-up intake of 1287.2 g ETOH
per month yielded in significant increases in physical
health and well-being by 11% and decreases in
Effect on the risk for stroke
biomarkers (γ-GT or mean corpuscular volume) in heavy
One meta-analysis (Ronksley et al. 2011) on alcohol and drinkers (Heather et al. 1987), a stronger decrease in
stroke risk was detected (Table 2). Here, this recent alcohol intake (pre-treatment: 184 g ethanol per day,
analysis of longitudinal cohort studies showed that post-treatment: 97 g ethanol per day) even led to
alcohol-drinking individuals compared with non-drinkers decreases in severity of alcohol dependence and neurotic

psychopathology, besides improved physical symptoms to matched psychiatric in-patients. Overall, the authors
and biomarkers such as γ-GT and mean corpuscular volume reported positive therapeutic mid-term results: Based on
in patients with problematic alcohol use (Potamianos a 5-year follow-up of the hospital data records, patients
et al. 1986). In line with these RCT findings, a longitudi- who received one of the brief interventions differed signif-
nal cohort study of 1-year follow-up period conducted by icantly regarding the survival time until the first alcohol
Shaw et al. (1998) in alcohol-dependent patients event after the intervention from the matched in-patient
described significant improvements regarding their levels group without brief intervention (mean 1,261 days of
of depression (i.e. moderate or severe; pre-treatment 38% sobriety compared with mean 1,092 days). Additionally,
of patients to 1-year follow-up: 25% of patients), level of individuals in the intervention group displayed signifi-
social stability and also in alcohol-related physical and cantly longer survival time to psychiatric in-patient
social problems in abstinent patients, but also in patients episodes and suffered approximately half as many
who reduced their alcohol intake over the past 6-month episodes in total over the 5 years of observation compared
period (pre-treatment: patients mean 37,251 kg ETOH with the matched individuals (adjusted for the number of
per 6 months to 1-year follow-up: mean 9,630 kg ETOH mental health events 1 year prior to the intervention).
per 6 months). Also within 1-year follow-up, frequency According, matched control in-patients spent
of out-patient services (4.95 to 2.77 visits) or use of significantly more days in the hospital in total because
religious or social support services (e.g. Alcoholics of additional psychiatric episodes than intervention
Anonymous; 4.87 to 1.58 visits) decreased significantly participants. Concluding, interventions aiming at alcohol
in patients with at least 75% alcohol reduction. The reduction promote both mental and physical health
stronger the reduction of frequency, duration and benefits and thus also offer potential socioeconomic
amount of drinking, the greater was the patients benefit savings. The observation of approximately 800 less
(Shaw et al. 1998). Noteworthy, previous moderate or psychiatric in-patient admissions following an initial brief
severe anxiety levels, self-esteem ratings and content- intervention could save more than $US1,000 per patient
ment with one’s life situation also improved significantly in terms of cost benefits for the health-care system (Hulse
in patients who displayed ‘unchanged’ drinking behavior & Tait 2003). Here, caution has to be paid to the fact,
over the entire observation period. But one has to be that in this study, indicators reflecting alcohol limitation
aware that even those patients did reduce their consump- were days of sobriety, which differs from those variables
tion (i.e. daily intake on heavy-drinking days, abstinence reported earlier in other alcohol reduction studies.
days, physical and social complications of drinking), but Because of adding important findings in the context of
failed to achieve the reduction criterion of more than alcohol reduction effects on mental and physical health
50% of their former alcohol intake. Despite vast similarity (costs) in patients with evident alcohol use disorder, this
across examined patients, at baseline, those categorized study was included in this systematic review.
as ‘unchanged’ patients were younger, and those who Furthermore, alcohol reduction was seen to help as a
could establish ‘controlled drinking’ (i.e. consuming first step to provide a qualified (in-patient or out-patient)
mean 36 g ETOH per week over time) were ‘less heavily detoxification (Craig et al. 2011), thus avoiding aversive
dependent’ (Shaw et al. 1998; p.301); thus representing side effects of sudden alcohol cessation like alcohol
the diverse patients cohorts seen in daily in-patient care withdrawal syndrome (Shaw et al. 1998). Shaw et al.
for alcohol use disorders. Nonetheless, it remains unclear (1998) could already predict in their patients that
whether the found increases in psychological health (among previous history of withdrawal and more than
variables as well as improvements in other outcome four withdrawal episodes) also baseline consumption
variables may also be evident in patients who truly did above 216 g pure alcohol on heavy-drinking days led to
not change their alcohol use. If that would be the case, a fourfold increased risk of a severe withdrawal syndrome
improvements would be attributed to other reasons than (32% versus 7.3%) or to a doubled risk for significant
alcohol reduction. Limiting, this cannot be ruled out by complication of withdrawal (12.6% versus 7.3%), which
lack of accuracy in this drinking status category. No in turn also predicted a worse treatment outcome.
further alcohol reduction effects were observed in control Similarly, Craig et al. (2011) reported that only 0.5% of
of drinking problems (Heather et al. 1987), nor in marital the severely alcohol-dependent individuals who partici-
status or employment, respectively (Shaw et al. 1998). pated in a self-paced, medication-free alcohol reduction
In regard of specific populations, psychiatric patients program (and reduced intake from approximately 200 g
previously reduced their drinking to a significant higher ETOH per day to 120 g ETOH per day) over 10 days prior
extent than general medical patients (Potamianos et al. to detoxification experienced withdrawal seizures. In
1986). Also, Hulse and Tait (2003) investigated longitu- contrast, 17.2% of this sample reported having seizures
dinal effects of alcohol reduction in a cohort of psychiat- during earlier treatment occasions without a preliminary
ric in-patients with alcohol use disorder in comparison alcohol reduction (Craig et al. 2011). As part of the

program, participants received, on the one hand, patients with different severity levels of alcohol
recommendations like substitution of strong liquors by dependence can achieve after limiting their alcohol
low-alcohol drinks, delay of drinking by 30 to 60 minutes intake to different degrees possible. Because, according
and not to drink to get drunk. On the other hand, to clinical experience, problematic alcohol use often
participants who suffered aversive withdrawal symptoms co-occurs with other psychiatric illnesses and is observed
due to speeded alcohol reduction were given advice to more often in psychiatric patients than in other subjects,
drink alcohol in order to reduce these symptoms, but two studies (Potamianos et al. 1986; Hulse & Tait 2003)
not more than 16 g alcohol (equals 2 alcoholic drinks). even demonstrated in this specific population that alcohol
After 30 minutes, individuals should check their reduction can lead to beneficial effects. Moreover, lower-
condition again and follow this strategy until withdrawal ing alcohol use and thus lowering severity of withdrawal
symptoms were bearable (Craig et al. 2011). syndrome may also be an important issue in preparation
Evaluating the study populations included in this of further treatment steps as shown by Shaw et al. (1998)
section, two studies (the RCT by Potamianos et al. 1986 and Craig et al. (2011).
and the prospective cohort study by Hulse & Tait 2003)
examined psychiatric in-patients (and general medical
Effects of alcohol reduction on social functioning
hospital patients too; Potamianos et al. 1986) who had
alcohol-related problems (Potamianos et al. 1986) or We found eight studies eligible for the investigation of
displayed hazardous, harmful or dependent alcohol alcohol reduction effects on social functioning (Table 2).
consumption (Hulse & Tait 2003). Noteworthy, Hulse Of those, seven studies were conducted in RCT design
and Tait (2003) excluded patients diagnosed as alcohol (Brown 1980; Fitzgerald & Mulford 1985; Scott &
dependent by the Severity of Alcohol Dependence Anderson 1991; Anderson & Scott 1992; Sitharthan
Questionnaire (Stockwell et al. 1979) and referred them et al. 1996, 1997; Kraemer et al. 2002) and one was
to an intensive treatment, but included patients fulfilling the aforementioned prospective cohort study by Gual
criteria of alcohol dependence by the AUDIT (Babor et al. et al. (2009).
2001); assuming a selection of ‘less severe dependent’ All seven prospective RCTs found significant alcohol
study participants appropriate for alcohol reduction reduction effects. Those ranged from improvements in
treatment, which limits the generalizability of findings severity of alcohol dependence symptoms by 4–76%
and range of application in patients with alcohol use (Anderson & Scott 1992; Sitharthan et al. 1996, 1997),
disorder. Heather et al. (1987) recruited individuals from perception of control over drinking by 20–68%
general practitioners practices where subjects’ severity of (Sitharthan et al. 1996, 1997) to increases of self-efficacy
alcohol use disorder also ranged from having no problems in controlled drinking by 87–115% (Sitharthan et al.
with alcohol or dependence symptoms to severe problems 1997) over the period of 6-month follow-up (Sitharthan
with severe physical dependence on alcohol (Heather et al. 1997) or 12 months, respectively (Brown 1980;
et al. 1987). Concerning the alcohol use measures, as a Fitzgerald & Mulford 1985; Scott & Anderson 1991;
benefit, both RCTs verified patients’ information on Anderson & Scott 1992; Sitharthan et al. 1996). RCTs
alcohol consumption via significant others (Potamianos also reported significant reductions in overall alcohol-
et al. 1986); at least for about half of the study subjects related problems (i.e. 8% fewer problems at work or less
(Heather et al. 1987). In the prospective cohort studies, injuring another person, 28% fewer health problems
detailed reconstruction of drinking was obtained by an and 33% less concerns by others; Sitharthan et al.
experienced researcher via interview of patients only at 1996) and improved physical and mental health and
baseline and at follow-ups (Shaw et al. 1998), or by fewer alcohol-related adverse consequences (e.g.
patients’ self-report 24-hour drink diaries (Craig et al. interpersonal, intrapersonal, social, physical and
2011). Again, days of sobriety were used to measure impulsive behavior, no further quantified; Kraemer et al.
alcohol reduction by Hulse and Tait (2003). As a major 2002). Interestingly, when latter analyses excluded
limitation, it remains unclear whether Potamianos et al. alcohol-dependent individuals, significant changes in
(1986) observed decreases in outcome measures accom- physical health after 30% alcohol reduction became
panied with alcohol reduction were of statistical signifi- non-significant, highlighting that especially those severe
cance, because no detailed information was given. A patients benefit from such a treatment approach;
further limitation was that Heather et al. (1987) only alcohol-related adverse consequences remained about
reported usage of a self-completion questionnaire of no the same with no improvements in those who did not
further reference, in order to assess physical health, reach this reduction cut-off (Kraemer et al. 2002). Other
well-being as well as control of drinking. RCTs found further significant improvements of
Altogether, these findings may display the range of alcohol-related social problems by 8%/9% (Anderson &
mental and physical overall health improvements Scott 1992), or reduction of alcohol-related driving

incidents by more than 50%: (1) fewer drinking and driv- Scott & Anderson 1991; Anderson & Scott 1992;
ing episodes (annual incidence of 7.25 versus 32.4 or Sitharthan et al. 1996, 1997; Kraemer et al. 2002).
23.95 episodes of comparison groups), (2) fewer persons Here, alcohol consumption outcome measures and
having drinking and driving episodes (4 versus 12) as quantities differed and changed greatly between studies:
well as (3) significant psychosocial improvement (domes- from lowest amounts like baseline 29.5 to follow-up
tic, vocational, interpersonal, social and health status) 14.05 drunk days past 90-days assessment, assuming
(Brown 1980). Additionally, Fitzgerald and Mulford ≥80 g pure alcohol per day (Brown 1980), or 36.4/
(1985) reported a direct mirroring of alcohol-dependent 36.2 g* (pretest) to 22.9/16.2 g* alcohol per week
patients’ subjective perception of life quality by their (post-test) (Sitharthan et al. 1996) to higher amounts
reported drinking behavior changes: while the majority of pre-treatment 1214 g ETOH per month to follow-up
of the patients subjectively perceived their drinking 319.5 g ETOH per month (Kraemer et al. 2002), or
behavior as improved since treatment discharge by about baseline intake of 80.8 g* ETOH per occasion with
74% to 95% accompanied with 73% to 85% improved 21.6/18.4* mean days per month to post-treatment in-
quality of life, no change in drinking was perceived by take of 30.8/50.9 g ETOH* per occasion with 6.2/11.9*
up to 20% of patients with up to 18% reporting similar mean days per month (*per intervention group)
quality of life since treatment discharge, and 5% to 6% (Sitharthan et al. 1997), or even from baseline con-
of patients reporting drinking worsening together with sumption of 330 g/399 g to 525 g ethanol weekly (de-
5% to 9% of patients reporting worsening of life quality pending on the data analysis approach; Anderson &
(Fitzgerald & Mulford 1985). Scott 1992). Further significant beneficial changes in
In regard of changes in explicitly addressed alcohol- drinking behavior were detected after significant
related relationship problems, only one RCT found that decreases in the longest period of continuous drinking
limited alcohol intake was accompanied with lowering (from baseline 8 hours to 5 hours post-intervention),
of percentage by 35–46% in patients reporting relation- enlongeing of periods with drinking below three drinks
ship problems (Sitharthan et al. 1997). Sitharthan et al. per day (i.e. 30 g ETOH per day; 3 days at pretest to
(1996) also first found a decrease in relationship 7 days at follow-up), or drinking days (i.e. ≥2 alcohol-
problems within the first 6 months of observation by a free days per week; not further quantified), or
significant 19%, but then those problems increased again improvements in symptoms such as early morning
by 12% within the next 6 months of follow-up, thus drinking, guilt and remorse after drinking and inability
resulting in statistically unchanged mode (Sitharthan of remembering the night before drinking (Sitharthan
et al. 1996), pointing to the fact that some improvements et al. 1996). Moreover, alcohol outcome measures were
might only be of transient nature and longer observation defined as total abstinence, drinking less than 4 days or
periods may help to identify beneficial changes of more still drinking but without fulfilling ‘alcoholic’ fashion as
persistent nature. defined by the Alcoholic Stage Index (Mulford &
Contrary, three RCTs described that alcohol reduction Fitzgerald 1977; Fitzgerald & Mulford 1985).
did not affect rates of job loss (Sitharthan et al. 1997), Study cohorts ranged from male drunk drivers
injuries to others (Sitharthan et al. 1997), psychological (reflecting a specific, heterogeneous cohort in which
well-being (e.g. general health, life quality/satisfaction, individuals were sentenced to attend periodic detention
affect balance, anxiety; Anderson & Scott 1992; Scott & and 61.6% being identified as alcohol dependent; Brown
Anderson 1991), frequency of exercise (Scott & Anderson 1980), or problem drinkers (who acknowledged problems
1991; Anderson & Scott 1992), body weight dieting in controlling their alcohol intake; Sitharthan et al. 1996,
(Scott & Anderson 1991; Anderson & Scott 1992), 1997) or were at-risk drinkers (Kraemer et al. 2002),
smoking (Scott & Anderson 1991; Anderson & Scott heavily drinking men (Anderson & Scott 1992) or
1992), laboratory markers (e.g. γ-GT, mean red cell corpus- women (Scott & Anderson 1991), or alcohol-dependent
cular volume; (Anderson & Scott 1992; Scott & Anderson in-patients (Fitzgerald & Mulford 1985) or alcohol-
1991), or consultation rates or episode rates within the dependent out-patients (Kraemer et al. 2002); please see
followed year (Scott & Anderson 1991; Anderson & Scott also for alcohol intake criteria Table 2. Here, some studies
1992). Cautionary, because of low incidence rates, no excluded individuals with high or severe alcohol
changes in job losses or legal problems could be further dependence (according to a score of 30 or above on the
analyzed in some cases (Sitharthan et al. 1996). Severity of Alcohol Dependence Questionnaire; SADQ-
However, these previously described effects were C), thus including subjects with mild to moderate alcohol
detected after alcohol reducing, which comprised in dependence symptoms only (mean SADQ-C score of ~19;
detail: reduced frequency of alcohol intake by 35–71% SD 1.4/1.8) (Sitharthan et al. 1997). Other trials in-
(Brown 1980; Sitharthan et al. 1997), and 17–57% re- cluded subjects with mild to severe alcohol dependence
duced amount of drinking (Fitzgerald & Mulford 1985; levels as operationalized by the SADQ-C scoring

(Stockwell et al. 1979), although the mean of the study Subgroup-specific alcohol reduction
sample was identified as mildly affected individuals
Adolescents and young adults
(Sitharthan et al. 1996).
As limitations, two trials included small-sized samples Based on the estimation of an alcohol-associated
of n = 22 and n = 20 per group (Sitharthan et al. 1997), mortality rate of 10% in female and 25% in male young
or n = 20 per group and further n = 7 dropping out persons in the European Union, this population seems
(Brown 1980), respectively. Other caveats refer to the specifically vulnerable to adverse consequences of
usage of dichotomized assessment of alcohol-related harmful alcohol consumption (Mathurin et al. 2012).
problems (i.e. ‘normal’ versus ‘abnormal’ according to a Worldwide among young persons, alcohol is even related
cut-off score) based on the participant’s answers in the to the three leading causes of death: unintentional
respective questionnaires (Scott & Anderson 1991; injuries, homicide or suicide (McBride et al. 2004; p.
Anderson & Scott 1992). Although Sitharthan et al. 279). Because adolescent heavy episodic drinking is
(1997) also found significant improvements in regard to related to increased long-term health risks in adulthood
problems at work, legal trouble and health problems, (Oesterle et al. 2004) or legal problems (McMurran
these findings were not described earlier, because only 1991), intervention programs addressing alcohol harm re-
one of the treatment groups showed them which may duction are specifically targeted at adolescents and young
be rather due to treatment effects than to lesser alcohol adults. In order to protect adolescents from these detri-
intake (Sitharthan et al. 1997). mental consequences, alcohol prevention programs were
Noteworthy, besides assessment via self-monitored developed and offered in schools or colleges and
drinking measures such as diaries or questionnaires universities. Here, especially prevention approaches
(Brown 1980; Fitzgerald & Mulford 1985; Scott & aiming at harm reduction appear to be more effective than
Anderson 1991; Anderson & Scott 1992; Sitharthan those pursuing abstinence or delayed alcohol use
et al. 1996, 1997; Kraemer et al. 2002), some (McBride et al. 2004; Newton et al. 2009, 2011; Vogl
authors applied confirmation of drinking by et al. 2009). In that, and for investigating whether
collaterals in a small subsample validating the self- reducing alcohol intake in adolescents affects physical or
reported data of the study subjects (Sitharthan psychological factors, we identified four studies in this spe-
et al. 1996). cific subgroup; three RCTs (Kypri et al. 2009; Newton et al.
Finally, similar positive changes were seen in the 2009; Vogl et al. 2009) and one quasi-experimental trial
aforementioned, longitudinal Spanish study by Gual (McBride et al. 2004) (for study overview, see Table 2).
et al. (2009), where patients underwent a treatment Two cluster RCTs (Newton et al. 2009; Vogl et al.
program for alcohol dependence (lasting 2 years) and 2009) and the included quasi-experimental trial
were reassessed after 20 years. The follow-up showed (McBride et al. 2004) were conducted in school students
that of the initial cohort of 850 detoxified aged 13 years on average in order to primarily evaluate
alcohol-dependent patients, 24 patients practiced the effects of implemented alcohol harm minimization
controlled alcohol intake and 277 did not drink alcohol school programs. Both Newton et al. (2009) and McBride
at all; however, both groups displayed similarly lower et al. (2004) observed a significant gain of alcohol-related
psychosocial stress levels and better social functioning knowledge (and harm minimization knowledge in partic-
than the 87 remained heavy drinkers (Gual et al. ular) directly and sustainably 6 months after the inter-
2009). Further, compared with heavy drinkers and vention program (Newton et al. 2009), which
abstinent patients, controlled drinkers showed lower converged in the long run of the 32-months follow-up to-
rates of long-term incapacity (7.7% controlled drinkers ward the control group level but was still 4.5% higher
versus 22.1% heavy drinkers; 13.1% abstainers). Fewer than that of controls (McBride et al. 2004). In contrast
socio-legal problems were detected in controlled drinkers to the control groups, pupils of the intervention groups
as well in abstainers compared with heavy drinkers also developed significantly safer alcohol-related attitudes
(3.8%/4.3% versus 12.6%) (Gual et al. 2009). For study throughout the 32 months study (McBride et al. 2004),
quality evaluation, please see earlier section ‘effects of or significantly less greater increases in alcohol-related
alcohol reduction on hospitalization, injuries and expectancies over 12 months of follow-up (Vogl et al.
mortality rates’. 2009), and experienced less harm associated with own
Altogether, various social functioning and life alcohol use by 22.9% than controls (McBride et al.
qualities improved significantly as soon as alcohol 2004). Vogl et al. (2009) only observed this lower in-
consumption was sustainably reduced or total crease of harm experiences in their female intervention
abstinence was reached in mostly examined alcohol- cohort (baseline/12-months follow-up; female interven-
dependent individuals with hazardous or harmful tion group: 2.33/3.30 harms versus female control
drinking patterns. group: 2.21/7.15 harms versus male intervention group

4.49/11.67 harms); boys of the control group were reviewed studies used self-completion surveys or ques-
similar to the boys in the intervention group. No signifi- tionnaires for all alcohol and outcome measures without
cant differences were found between groups for harm outer validation by bio-parameters or collaterals, respec-
caused by other’s alcohol use (McBride et al. 2004). tively, which includes the risk of answering in a social de-
These positive outcomes were accompanied by an sirable manner (means underreporting), albeit these
immediate reduction of weekly alcohol consumption by assessments were conducted anonymously (McBride
17.5 g ethanol (but no longer at 6 months follow-up) in et al. 2004; Newton et al. 2009; Vogl et al. 2009). Also,
the intervention group compared with increasingly the utilized multi-level analyses are assumed to produce
drinking controls, who were given only regular informa- over-conservative results (McBride et al. 2004).
tion about alcohol and drugs in school (Newton et al. Contrary to these beneficial findings, another
2009), or less total alcohol consumption (9.2% less than Australian RCT did not find significant positive alcohol
controls), particularly less harmful and hazardous drink- reduction effects in regard to personal, social, sexual,
ing (4.2% less than controls) (McBride et al. 2004). It legal or academic alcohol-related problems (Kypri et al.
should be noted that alcohol consumption did increase 2009). However, the authors reported indeed a reduction
over the study period in both groups according to age- in total weekly alcohol intake by 17% in young, harmful
related trends, but with the aforementioned significant drinking university students after 1 month following
differences (McBride et al. 2004). Additionally, McBride intervention and a sustained 11% weekly alcohol
and colleagues assessed 36.3% more non-drinking pupils decrease at 6 months past intervention compared with
after intervention at the 32 months compared with the control students not receiving any intervention (medians
control group (starting from no significant baseline differ- for 1-month follow-up: 80 g ETOH/week versus 100 g
ences between groups) (McBride et al. 2004). In line, Vogl ETOH per week, 6-month follow-up: 110 g ETOH per
et al. (2009) reported that after the intervention program week versus 90 g ETOH per week) (Kypri et al. 2009).
the weekly average alcohol intake and the frequency of And noteworthy, also controls did reduce their binge
binge drinking (for definition, see Table 3) remained ben- drinking behavior (4/6 drinks of 10 g ETOH in
eficially at relative constant level (baseline/12 months women/men); of the 100% baseline of these students,
follow-up; weekly alcohol use: mean 6.6 g/9.9 g ethanol; only 58.6%/54.5% reported binge drinking at
frequency of binge drinking: .21/.38 times per 3 months) 1 month/6 months (Kypri et al. 2009). Finding no effects
in female 8th graders over a time period of 12 months here could also be explained by answering questions on
compared with an observed age-related increase in (fe- alcohol or personal problems in a social desirable
male) controls (baseline/12 months follow-up; weekly al- manner, especially when assessed via self-reports, which
cohol use: mean 3.5 g/22.5 g ethanol; frequency of binge implies the risk of underreporting (Kypri et al. 2009).
drinking: 0.18/0.93 times per 3 months) or male inter- Additionally, for the interested reader and in reference
vention group students (baseline/12 months follow-up; for the effectiveness of different social norms intervention
weekly alcohol use: mean 15.6 g/38.6 g ethanol; fre- approaches to reduce alcohol misuse in young American
quency of binge drinking: 0.39/1.07 times per 3 months); and New Zealand college and university students, there is
again, boys of the control group were similar to the boys a very well-illustrated Cochrane data-based systematic
in the intervention group. Of note, standard drink conver- review by Moreira et al. (2009), where none of the
sions (one standard drink contains 10 g ethanol) were previously mentioned studies were included. Based on
based on the Australian Alcohol Guidelines (National 22 RCTs, the authors found that some but not all
Health and Medical Reasearch Council 2001) as referred normative approaches resulted in short-term and
to in the RCTs (Newton et al. 2009; Vogl et al. 2009). mid-term lowering of alcohol (mis)use and thus
Newton et al. (2009) remarked that school-based pre- alcohol-associated harm (i.e. consequences of alcohol
vention programs are usually effective only after such as adverse legal events, inappropriate risky
12 months of intervention, so that is maybe why no addi- behavior, injuries and illicit drug use) (Moreira et al.
tional effects were found in their study. As a potential bias 2009; results overview in Table S2). Furthermore, a
of results, the attrition of pupils at high risk (e.g. higher review by Wachtel and Staniford (2010), which partly
alcohol intake, less alcohol-related knowledge but high included the same results in adolescents and young
expectancies and harm experiences) could cause loss of adults at ages 12–25 years with a focus on sustainability
power to detect the true nature of alcohol reduction ef- of brief interventions in clinical settings, summarized that
fects past these interventions, which may result in either 7 out of 14 reviewed studies reported short (up to
underestimation of findings given the intervention would 6 months), medium (6–12 months) and long-term (more
have affected these pupils, or overestimation of results than 12 months) harm reduction benefits in association
given the intervention would have failed in those pupils with reduced alcohol intake (drinking frequency and
(Newton et al. 2009; Vogl et al. 2009). Further, all alcohol amount, including binge drinking).

In light of these study results, there are clear short- from initial five down to three in the previous 30 days
term and long-term benefits from alcohol reduction in in comparison with women with problematic alcohol
adolescents and young adults, although it needs to be use but without interventions, who also displayed
noted that the shown results were clearly intervention sustained decreases in alcohol use (Manwell et al.
program effects, which might deviate from those only 2000). No further significant health benefit was seen
seen past ‘pure’ alcohol reduction without education on regarding general health status, cigarette consumption,
alcohol-related harms. Here, harm-minimizing depressive symptoms, injuries or accidents (Manwell
approaches did result in less alcohol-related experienced et al. 2000). However, during the 48-month follow-up
harms in female 8th graders or dampened alcohol- period, 22 women in the intervention group became
associated, social-benefiting expectancies in pupils 1 year pregnant and sustainably decreased their alcohol use
after intervention. The one here included original study per week (baseline 163.2 g to 42 g ETOH per week) and
in university students did not find further effects past binge drinking episodes per month (5.7 to 1.5 episodes
alcohol reduction, although previously beneficial results per month) to a statistically higher extent than the 19
could be observed. women of the control group, who also became pregnant
(baseline/48 months: 162 g to 121.2 g ETOH per week;
5.5 to 4.2 episodes per month) (Manwell et al. 2000).
Pregnant women and women of childbearing age
Unfortunately, no further effects on the course of preg-
High alcohol consumption during pregnancy has terato- nancy or onto the baby have been documented (Manwell
genic effects on the fetal development and thus contrib- et al. 2000). Interviews were conducted by researchers
utes to physical, cognitive and emotional impairments who assessed data including alcohol use via the Timeline
and behavioral deficits as seen in fetal alcohol syndrome Followback Method (Sobell & Sobell 1995a), but with no
or fetal alcohol spectrum disorders (Coles et al. 1991; further validation by biomarkers; however, family mem-
Chang et al. 1999; Robinson et al. 2010). Keep in mind ber interviews were conducted within the study and
that alcohol levels in the fetus are similar to those in verified that there were no systematic differences from
the maternal blood during pregnancy and is further participants self-reports (Manwell et al. 2000). It should
delivered partially through mother’s milk during nursing be further noted, that these female study participants
period (cf. Little et al. 1989; p.425). In order to prevent were also included if they had mental disorders or illicit
these risks, early interventions are indicated in pregnant drug use in the past, which supposes to represent the typ-
women or women of childbearing age, because the level ical population of primary care clinic settings (Manwell
of alcohol intake prior to and during early pregnancy et al. 2000). This, however, may bias effects, which may
can predict subsequent drinking level during later preg- have been possibly seen after alcohol reduction especially
nancy (Chang et al. 1999; Manwell et al. 2000). in (mental) health status (Manwell et al. 2000). Other-
We therefore found six studies eligible for inclusion in wise, females were excluded, if they were considered to
this review section. One RCT investigated alcohol reduc- be alcohol-dependent (e.g. having withdrawals in the
tion effects in women of childbearing age (Manwell past, getting medical advice for treatment or undergoing
et al. 2000); whereas one meta-analysis (Patra et al. alcohol treatment) (Manwell et al. 2000). As found, both
2011), one RCT (Chang et al. 1999) and three longitudi- groups did reduce sustainably their alcohol consumption,
nal cohort studies (Little et al. 1989; Coles et al. 1991; which is argued by the authors to be due the intervention
Robinson et al. 2010) examined the short-term and effect of follow-ups, and furthermore, a ≥20% alcohol
long-term effects of different levels of alcohol intake dur- reduction difference between the groups was predicted
ing pregnancy and after delivery on birth outcome and by exposure to the personal intervention, which may also
infants development (for study details, see Table 2). be taken into account when evaluating other (evident)
Positive intervention effects were found in an RCT effects following alcohol reduction outside this study
including 454 women of childbearing age, who were (Manwell et al. 2000).
not pregnant at the time of recruitment, but displayed A meta-analysis of 36 case-control and cohort studies
problem drinking (>132 g but not more than 672 g provides evidence of a dose dependency of alcohol
alcohol per week or > 4 drinks per occasion or gave ≥ 2 consumption during pregnancy and its consequences
positive answers to the CAGE questionnaire; Ewing for relative birth risks: low birth weight risk (<2500 g)
1984), and whose alcohol intake and health status were rises linearly up to a 7.5 folded risk with a daily intake
followed for 48 months (Manwell et al. 2000). After initial beginning from 10 g to 120 g pure alcohol compared
interventions, these women reduced significantly their with abstinence, with a twofolded risk already becoming
drinking amount by 48% (i.e. from baseline 168 g to apparent after daily consumption of 52 g ETOH (Patra
90 g ETOH per past week) and their number of binge et al. 2011). Concerning the relative risk of preterm birth
drinking episodes (intake of >48 g ETOH per occasion) (<37 weeks of gestation), women drinking while

pregnant at a level of 36 g per day displayed a 23% only (i.e. control condition), respectively (Chang et al.
increased risk in comparison with non-drinking pregnant 1999). Pre-assessment intake during pregnancy was
women; this association was not detectable at an daily 17.76 g/24.86 g ethanol per drinking day, respectively
intake level of <19 g ethanol (Patra et al. 2011). (Chang et al. 1999). It needs to be noted that, on one
Maternal alcohol use above 10 g ethanol per day was hand, women who did not change their drinking levels
associated with a linearly increased risk of ‘small for ges- during pregnancy were excluded from the analysis of
tational age’ (SGA; below the 10th percentile) compared net changes, which might have masked true rates of
with abstinent mothers (Patra et al. 2011). In light of women beneficially changing their alcohol consumption
their pre-pregnancy alcohol use in women, additional levels for the sake of their unborn babies. Although
sensitivity analyses showed that relative birth risks were comparisons between both total groups did not yield
associated without a risk of <30 g ethanol per day (low significant differences in regard of newborn outcome
birth weight), <50 g ethanol per day (preterm birth) variables (birth weight and APGAR scores), unfortu-
and <18 g ethanol per day (SGA); similar results were nately, associations between these birth outcomes and
found with adjustments at least for confounders like antepartum or total prenatal maternal drinking were
smoking (Patra et al. 2011). Overall, although most of not established. Thus, the influence on these birth
the studies included in this meta-analysis did adjust for variables of the observed net decreases in alcohol use
possible confounding variables such as smoking, socio- cannot be evaluated (Chang et al. 1999). On the other
economic status, body mass index or ethnicity, the au- hand, also thoroughly abstinent women were excluded
thors still assume the possibility of further unmeasured from analysis, which limits the possible influence of the
confounders to affect the results (Patra et al. 2011). Fur- previously mentioned ‘healthy-drinkers effect’, because
thermore, differences in interview or self-report assess- those women were significantly of higher risk obstetrics
ment methods of alcohol and outcome measures can than prenatally drinking women (51.7% versus 34.6%)
influence findings as well, because no further indicators (Chang et al. 1999). While alcohol consumption and
like bio-parameters were used. Here, especially, the related problems were assessed via interviews using
authors consider potential recall bias occurrence through established instruments (e.g. the Timeline Followback
women with adverse pregnancy outcomes who may have (Sobell & Sobell 1995a), SCID for DSM-III-R (Spitzer
under-reported their alcohol use versus women with et al. 1990), AUDIT (Babor et al. 2001)), no further
good pregnancy outcomes who may not have under- confirmation of assessed data was obtained, which does
reported their alcohol levels or women having trouble not allow for correction of under-reported maternal
in correctly reporting their alcohol intake during preg- alcohol intake (Chang et al. 1999). This study excluded
nancy when asked post-partum (Patra et al. 2011; women fulfilling DSM-III-R criteria (Spitzer et al. 1990)
p.1416). Another bias may be seen in the ‘healthy- for current alcohol or other substance abuse or
drinkers effect’, which resembles the notion of the afore- dependence, but included women with lifetime diagnoses
mentioned ‘sick-quitting effect’, means women being (Chang et al. 1999), narrowing the results to those
abstinent during pregnancy because of poorer health without alcohol-related problems and those ones who
histories prior to becoming pregnant (Patra et al. 2011). currently mastered substance abuse or dependence
This meta-analyses is also based on studies daily or according to DSM-III-R.
monthly average consumption rates only, which leaves As a further step, examining long-term effects of
out the examination of differentiated effects of ones’ alcohol-exposed children, the longitudinal cohort study
drinking pattern, which have been shown to be relevant by Coles et al. (1991) reported that continued prenatal
in terms of fetal and postnatal development (Patra et al. alcohol use throughout pregnancy with high average
2011). Despite this, no publication bias was found (Patra intake of 279.66 pure alcohol per week affects sustain-
et al. 2011), and none of the previously reviewed original ably the unborn child because of alcohol’s teratogenic
studies were included in this meta-analysis. effects in terms of significant facial dysmorphia typical
Also regarding this specific time during pregnancy for prenatal alcohol exposure or significantly reduced
until short after delivery, an early RCT (which was not children’s head circumferences compared with
included in the meta-analysis of Patra et al. 2011 too) non-alcohol use; both effects were even evident at
investigated maternal alcohol consumption changes in children’s reassessment at their mean age of 5 years and
this sensitive period in women screened positive for risk 10 months. Generally, lower cognitive scores (seen as a
drinking in pregnancy via T-ACE (Sokol, Martier, & Ager potential basis of developing learning disabilities in later
1989); (Chang et al. 1999). The researchers observed in school life) were found in both children of mothers who
women of both study groups a ~20% net decrease of their drank through pregnancy (lowest scores) and even in
antepartum alcohol intake by 3.55 g/4.74 g ethanol per children whose mothers terminated heavy alcohol intake
drinking day after intervention and alcohol assessment by the second pregnancy trimester (average alcohol use

until cessation 271.14 g ethanol per week) compared levels (20–100 g ethanol per week) during the first preg-
with mothers who were not drinking during pregnancy nancy trimester was associated with lower risks of clini-
(Coles et al. 1991). This included children’s cognitive im- cally relevant externalizing (i.e. delinquency and
pairments in the domains sequential processing (e.g. aggression), internalizing and total behavioral problems
short-term memory/encoding, perceptual/motor coordi- in children at 14 years of age compared with maternal
nation), achievement (math skills, pre-reading identifica- abstinence (Robinson et al. 2010). Conversely to the
tion of letters and words) and mental processing study of Coles et al. (1991), this recent study did not ob-
composite score (reflecting the general intelligent score serve any statistical significant association between ma-
of a child) (Coles et al. 1991). All findings seen in children ternal heavy drinking (>110 g ethanol per week) and
exposed to alcohol during pregnancy were controlled for poor children’s behavioral outcome; but which was as-
the postnatal maternal alcohol consumption, advocating sumed to be influenced by the small subgroup sample size
that the observed effects may be attributable to prenatal (Robinson et al. 2010). The authors therefore assume
alcohol exposure rather than the influence of mothers that prenatal alcohol use and (neural and cognitive de-
current (high) alcohol use (Coles et al. 1991). However, velopmental) effects on the child behavior do not simply
the examined maternal study groups differed significantly follow a linear dose–effect relationship (Robinson et al.
regarding their smoking behavior (and regarding other 2010). For example, light to moderately drinking
potential confounding lifestyle factors too) and were not mothers may display better mental health and thus better
controlled for adverse nicotine effects (or other con- abilities to control alcohol use adequately during preg-
founders), which leads to difficulties in disentangling nancy compared with women with current problematic
(substance-)specific consequences. The small sample sizes alcohol use and abstinent women with maybe previous
(n = 21–25) did not allow for further subsampling in alcohol use problems, thus including the bias introduced
these cases (Coles et al. 1991). Nonetheless, the authors by sick-quitting mothers (Robinson et al. 2010). Addi-
assume that early alcohol exposure on the developing tionally, the previously shown findings on diverse somatic
fetus has been shown to have detrimental consequences; factors (e.g. cardiovascular events, type 2 diabetes and
the findings indicate that termination of drinking during stroke risk) found to be associated with a U-shaped curve
pregnancy may permit the opportunity of recovery regarding alcohol intake levels may also contribute to
regarding physical (e.g. head circumference) or cognitive these findings of lowered risks in a child’s development
development (Coles et al. 1991). However, the authors and light to moderate maternal drinking, assuming bet-
further caution that also other reasons may have caused ter health of the mothers, which in turn influences posi-
the differences seen between the groups: for example, the tively their behavior toward their child (Robinson et al.
average prenatal weekly alcohol intake given for both 2010). Methodological issues in this study should be
alcohol-drinking mother groups do not answer the ques- noted: self-reported alcohol quantities by the mothers
tion of what fetal effects are to be expected regarding only were used without further validation and not testing
exact timing, dosage and pattern of alcohol consumption for effects of maternal drinking patterns including binge
during pregnancy; also, other factors such as paternal drinking during first trimester. Beneficially, analyses were
influence need to be considered (Coles et al. 1991). adjusted for various (prenatal and perinatal) factors (e.g.
Although alcohol consumption was recalled by the maternal age, education, smoking, family income, func-
mothers at a post-partum interview, which may underlie tioning), which have been shown earlier to impact the re-
biases of social desirable answering or inaccurate recall, lationship of maternal alcohol intake during pregnancy
discontinuation of drinking was validated by family and child’s developmental outcome; inclusion of these
members or medical professionals (Coles et al. 1991). variables did not differ nature of findings but rather in-
Interestingly below those heavy-drinking levels, creased effect sizes (Robinson et al. 2010). A major
another 14 years long-term investigation of children’s strength of this study is the longitudinal design, which
development in reference to their mothers alcohol use may allow investigating developmental factors in a co-
during pregnancy found that low to moderate alcohol hort, unaffected by retrospective recall (which may simi-
consumption in the first pregnancy trimester (20–60 g larly apply to the previously reviewed prospective cohort
ethanol per week) did not result in negative, but surpris- studies in the previous sections) (Robinson et al. 2010).
ingly rather in positive effects in terms of child’s later Finally, Little et al. (1989) investigated the post-
internalizing (i.e. withdrawal, somatic complaints, partum influence of ethanol through breast milk on
anxious/depressed) and total behavior (based on the babies at year 1 and observed a highly significant, linear
CBCL score; Achenbach 1991) compared with children’s dose–response association between a babies’ alcohol ex-
behavior of mothers who did not consume any alcohol posure through breast milk during the 3 months of nurs-
during first trimester of pregnancy (Robinson et al. ing after delivery and adverse effects on the infantile
2010). Furthermore, even drinking at light to moderate psychomotor—but not mental—development in these

babies 1 year of age. Here, babies’ ethanol exposure on infant’s growth and cognitive development, even
through breast milk was approximated by weighting when drinking is terminated for the third trimester of
the ‘maternal absolute alcohol score’ for each month pregnancy. Also, infants’ exposure to ethanol through
(i.e. average maternal daily alcohol intake weighted breast milk is considered to affect negatively children’s
against maternal frequency of consumption) by the psychomotor development at year one. Besides drinking
breastfeeding days per month and additionally averag- amount, further relevant factors in light of fetal alcohol
ing these values over the observation period of effects are speculated, such as the drinking pattern, blood
3 months (Little et al. 1989; p.425). In detail and as a alcohol concentration and timing of alcohol exposure
conservative example, a daily maternal consumption during pregnancy, which need to be examined in future
of 23.68 g ethanol together with breastfeeding through- studies. Based on the reviewed findings and because of
out (which results in an infants’ exposure score of 1.0) a lack of universal guidelines for alcohol use (limits) in
predicted an decrease of 5.4 points on the Bayley Scale pregnant women, lowering alcohol intake to at least light
of Infants Psychomotor Development Index (Baylay levels should be promoted and supported in order to avoid
1969) in comparison with infants not exposed to etha- adverse consequences to delivery and children’s
nol during nursing at all (Little et al. 1989); including development.
all 400 mothers data in this analysis. This strong asso-
ciation was still found significant after excluding the DISCUSSION
four babies with the highest alcohol exposure rates or
ruling out other diverse (environmental) factors such Based on the knowledge that alcohol misuse causes a
as alcohol intake during pregnancy, smoking, mari- multitude of diseases (Mundle et al. 2003) and increased
juana or excessive caffeine use (Little et al. 1989). In- mortality (Di Castelnuovo et al. 2006; Rehm et al. 2011),
terestingly, Little et al. (1989) also figured out that we raised the question whether a reduction of the
the observed relationship did not only rely on the im- individual alcohol consumption can contribute to a
pact of binge drinking occurrence, because even those minimization of health risks within a harm reduction
mothers not binging at all on alcohol displayed the approach. In fact, this systematic review indicates that
same linearity between alcohol intake and child’s psy- interventions aiming at alcohol reduction (including total
chomotor skills. It has been speculated whether the abstinence as one possible therapeutic aim) indeed
brain is hypersensitive to even small amounts of etha- resulted in or were associated with positive effects in
nol or whether these ingested ethanol quantities accu- harmful, hazardous or alcohol-dependent drinkers. Major
mulate in the infant, which affects detrimentally benefits were observed for
motor skills (because of chronically sedating or neuro- • reducing alcohol-associated injuries (Dinh-Zarr et al.
anatomically damaging the brain); additional preclinical 2004; Borges et al. 2006);
and human studies are favoring the latter hypothesis • recovery of the ventricular heart function in alcoholic
(Little et al. 1989). Of note, it should be mentioned that cardiomyopathy (Nicolás et al. 2002);
the Baylays Development Indices are not very precise, • lowering of the systolic and diastolic blood pressure
and even a difference of 7 points in the psychomotor (Xin et al. 2001);
development scale is not assumed as ‘meaningful’ nor • normalization of biochemical parameters (e.g.
is this immediate score predictive of future child’s devel- glutamyltranspeptidase, aspartate aminotransferase,
opment (Little et al. 1989); however, these findings may triglyceride level, calcium, sodium and potassium)
be considered in terms of women’s postnatal, public (Hsieh et al. 1995; Yamada et al. 1997; Xin et al.
health advise. 2001);
Altogether, on the one hand, the reviewed studies on • body weight reduction (Puddey et al. 1992);
findings of alcohol effects in women in childbearing age • histological improvement in pre-cirrhotic
did not advocate any beneficial (health) effects after alcohol-related liver disease (Colman et al. 1980);
lowered alcohol intake. On the other hand, findings • slowed progression of an already existing
concerning alcohol effects in pregnancy support that alcohol-attributable liver fibrosis (Lieber et al. 2003);
drinking at low levels (<10 g ethanol per day in terms • preparation of a qualified detoxification by reducing
of low birth weight or ‘small for gestational age’, or adverse withdrawal symptoms (Craig et al. 2011);
<19 g ethanol per day for preterm birth, or 20–60 g • prevalence of psychiatric episodes and duration of
ethanol per week regarding long-term child’s in-patient hospital days (Hulse & Tait 2003);
development) were not associated with adverse effects • improvement of anxiety and depression symptoms,
on those (neonatal) outcomes. However, consuming self-confidence, contentment with one’s life situation,
above these limits, risks can increase linearly with and alcohol-related physical and social problems
alcohol intake, leading to detrimental long-term effects (Shaw et al. 1998);

• improved physical and mental quality of life and fewer of early initial screening for problematic alcohol use first
alcohol-related adverse consequences (Fitzgerald & and the sustained behavioral changes resulting in
Mulford 1985; Kraemer et al. 2002; Gual et al. 2009); effective harm reduction followed by specific intervention
• lower rates of long-term incapacity (Gual et al. 2009); programs in first contact medical health-care facilities.
• lower psychosocial stress levels and better social
functioning (Gual et al. 2009);
Acknowledgements
• no adverse neonatal effects for consumption below
cut-off rates of 10–18 g ethanol per day (Patra et al. This work has been supported by an unrestricted grant of
2011). Lundbeck GmbH to Dr. C.A. Müller and by grants to Prof.
The reviewed literature demonstrated remarkable Dr. A. Heinz by the Ministry of Education and Research
socioeconomic cost benefits in areas such as the medical (BMBF; 01ZX1311E/e:Med- program Alcohol Addiction;
health-care system or workforce productivity (Fleming Spanagel et al. 2013; and 01EE1406A), and the German
et al. 2002; Hulse & Tait 2003; Magnus et al. 2012). Research Foundation (DFG Exc 257, DFG HE2597/14-2
Thus, (at least) various economic savings suggest policy as part of DFG FOR 1617). We thank Dr. C.A. Müller
relevance for harm reduction approaches. for provision of counseling with the topic. Furthermore,
Individuals with heightened vulnerability do further we thank Prof. K. Mann, Prof. F. Kiefer, Prof. J. Rehm
benefit significantly by alcohol reduction, such as in and Prof. M. Roerecke for helpful advice during the
hypertension (Hsieh et al. 1995; Yamada et al. 1997), course of manuscript editing and A. Rosenthal for her
hepatitis C-virus infection (Lieber et al. 2003), psychiatric help in editing the tables.
co-morbidities (Hulse & Tait 2003), pregnancy and
breastfeeding period (Patra et al. 2011; Coles et al. AUTHORS CONTRIBUTION
1991; Little et al. 1989), but also among adolescents
and young adults (McBride et al. 2004; Newton et al. KC reviewed articles for eligibility and drafted the
2009, 2011; Vogl et al. 2009). manuscript. Selected articles were discussed between
Despite these findings, future studies are needed in the two reviewers KC and AH. AH provided critical
order to gain more knowledge about long-term effects, revision of the manuscript for important intellectual
for instance, in regard of the risk of developing cancer content. All authors critically reviewed content and
or mortality rates in persons who decrease their alcohol approved final version for publication.
intake. Here, epidemiological investigations could provide
further important information about alcohol–dose
relationships and thus help to derive future hypotheses References
(e.g. Little et al. 1989; Smith-Warner et al. 1998; Rehm, Achenbach T (1991) Manual for the Child Behavior Checklist/4-18
Patra, & Popova 2007; Lönnroth et al. 2008; Joosten and 1991 Profile. University of Vermont, Department of
et al. 2011; Patra et al. 2011; Rehm et al. 2011; Psychiatry: Burlington.
Anderson P, Scott E (1992) The effect of general practitioners’
Ronksley et al. 2011; Rehm & Roerecke 2013). Also,
advice to heavy drinking men. Br J Addict 87:891–900.
further studies should replicate and elucidate previous
Appel LJ, Brands MW, Daniels SR, Karanja N, Elmer PJ, Sacks FM
results, e.g. in light of ischemic and hemorrhagic (2006) Dietary approaches to prevent and treat hypertension:
stroke (Ronksley et al. 2011), or risks during and after a scientific statement from the American Heart Association.
pregnancy (e.g. Manwell et al. 2000). After all, future Hypertension 47:296–308.
studies may further help to identify cohorts who Babor T, Higgins-Biddle J, Saunders J, Monteiro M (2001) AUDIT:
The Alcohol Use Disorders Identification Test, Guidelines for Use in
benefit in particular from reduced alcohol intake, and
Primary Care, Second edn. World Health Organization:
may also elucidate gradual health effects accompany- Geneva.
ing steps of decreasing alcohol use (cf. Rehm & Balkau B, Vierron E, Vernay M, Born C, Arondel D, Petrella A,
Roerecke 2013). Ducimetiere P (2006) The impact of 3-year changes in
Concluding, the reviewed studies strongly support and lifestyle habits on metabolic syndrome parameters: the D.E.S.
I.R study. Eur J Cardiovasc Prev Rehabil 13:334–340.
emphasize the benefits of alcohol reduction in physical,
Barnard K, Sinclair JMA, Lawton J, Young AJ, Holt RIG (2012)
mental and societal health and life quality. Here, Alcohol-associated risks for young adults with Type 1
although these positive changes were associated with diabetes: a narrative review. Diabet Med 29:434–440.
decreased alcohol intake in individuals with a wide range Baylay N (1969) Manual for the Baylay Scales of Infant
of alcohol use levels, and conversely also beneficial effects Development. Psychological Corp.: New York.
Borges G, Cherpitel C, Orozco R, Bond J, Ye Y, Macdonald S,
of light to moderate drinking were found on
Rehm J, Poznyak V (2006) Multicentre study of acute
cardiovascular health, type 2 diabetes risk, and cerebral alcohol use and non-fatal injuries: data from the WHO
hemorrhage and ischaemic stroke risk, the reviewed collaborative study on alcohol and injuries. Bull World
studies particularly highlight the importance and benefits Health Organ 84:453–60.

Bottlender M, Spanagel R, Soyka M (2007) One drink, one long-term efficacy and benefit-cost analysis. Alcohol Clin Exp
drunk–controlled drinking by alcoholics? 3-year-outcome Res 26:36–43.
after intensive outpatient treatment. Psychother Friedenreich CM, Howe GR, Miller AB, Jain MG (1993) A cohort
Psychosom Med Psychol 57:32–38. study of alcohol consumption and risk of breast cancer. Am J
Brown RA (1980) Conventional education and controlled Epidemiol 137:512–520.
drinking education courses with convicted drunken drivers. Gapstur SM, Potter JD, Sellers TA, Folsom AR (1992) Increased
Behav Ther 11:632–642. risk of breast cancer with alcohol consumption in postmeno-
Chang G, Wilkins-Haug L, Berman S, Goetz MA (1999) Brief in- pausal women. Am J Epidemiol 136:1221–1231.
tervention for alcohol use in pregnancy: a randomized trial. Gual A, Bravo F, Lligoña A, Colom J (2009) Treatment for alco-
Addiction 94:1499–1508. hol dependence in Catalonia: health outcomes and stability
Coles CD, Brown RT, Smith IE, Platzman KA, Erickson S, Falek A of drinking patterns over 20 years in 850 patients. Alcohol Al-
(1991) Effects of prenatal alcohol exposure at school age. I cohol 44:409–415.
Physical and cognitive development. Neurotoxicol Teratol Guardia-Serecigni J (2011) A change of paradigm in the treat-
13:357–367. ment of low-severity alcohol-dependent patients. Adicciones
Colman JC, Morgan MY, Scheuer PJ, Sherlock S (1980) 23:299–316.
Treatment of alcohol-related liver disease with (+)- Hamajima N, Hirose K, Tajima K, Rohan T, Calle EE, Heath CW,
cyanidanol-3: a randomised double-blind trial. Gut Coates RJ, Liff JM, Talamini R, Chantarakul N, Koetsawang S,
21:965–969. Rachawat D, Morabia A, Schuman L, Stewart W, Szklo M,
Cox KL, Puddey IB, Morton AR, Beilin LJ, Vandongen R, Masarei Bain C, Schofield F, Siskind V, Band P, Coldman AJ, Gallagher
JR (1993) The combined effects of aerobic exercise and RP, Hislop TG, Yang P, Kolonel LM, Nomura AMY, Hu J,
alcohol restriction on blood pressure and serum lipids: a Johnson KC, Mao Y, De Sanjosé S, Lee N, Marchbanks P, Ory
two-way factorial study in sedentary men. J Hypertens HW, Peterson HB, Wilson HG, Wingo PA, Ebeling K, Kunde
11:191–201. D, Nishan P, Hopper JL, Colditz G, Gajalanski V, Martin N,
Craig M, Pennacchia A, Wright NR, Chase HW, Hogarth L Pardthaisong T, Silpisornkosol S, Theetranont C, Boosiri B,
(2011) Evaluation of un-medicated, self-paced alcohol Chutivongse S, Jimakorn P, Virutamasen P, Wongsrichanalai
withdrawal. PLoS One 6:e22994. C, Ewertz M, Adami HO, Bergkvist L, Magnusson C, Persson
Cushman WC (2001) Alcohol consumption and hypertension. J I, Chang-Claude J, Paul C, Skegg DCG, Spears GFS, Boyle P,
Clin Hypertens (Greenwich) 3:166–170. Evstifeeva T, Daling JR, Hutchinson WB, Malone K, Noonan
Cushman WC, Cutler JA, Hanna E, Bingham SF, Follmann D, EA, Stanford JL, Thomas DB, Weiss NS, White E, Andrieu N,
Harford T, Dubbert P, Allender PS, Dufour M, Collins JF, Walsh Brêmond A, Clavel F, Gairard B, Lansac J, Piana L, Renaud
SM, Kirk GF, Burg M, Felicetta JV, Hamilton BP, Katz LA, Perry R, Izquierdo A, Viladiu P, Cuevas HR, Ontiveros P, Palet A,
HM, Willenbring ML, Lakshman R, Hamburger RJ (1998) Salazar SB, Aristizabel N, Cuadros A, Tryggvadottir L, Tulinius
Prevention and Treatment of Hypertension Study (PATHS): H, Bachelot A, Lê MG, Peto J, Franceschi S, Lubin F, Modan B,
effects of an alcohol treatment program on blood pressure. Ron E, Wax Y, Friedman GD, Hiatt RA, Levi F, Bishop T,
Arch Intern Med 158:1197–1207. Kosmelj K, Primic-Zakelj M, Ravnihar B, Stare J, Beeson WL,
DHS (2010) German Centre for Addiction Issues. The Addiction Fraser G, Bullbrook RD, Cuzick J, Duffy SW, Fentiman IS,
Yearbook 2010. Geesthacht: Neuland. Hayward JL, Wang DY, McMichael AJ, McPherson K, Hanson
Di Castelnuovo A, Costanzo S, Bagnardi V, Donati MB, Iacoviello RL, Leske MC, Mahoney MC, Nasca PC, Varma AO, Weinstein
L, de Gaetano G (2006) Alcohol dosing and total mortality in AL, Moller TR, Olsson H, Ranstam J, Goldbohm RA, van den
men and women: an updated meta-analysis of 34 prospective Brandt PA, Apelo RA, Baens J, de la Cruz JR, Javier B, Lacaya
studies. Arch Intern Med 166:2437–2445. LB, Ngelangel CA, La Vecchia C, Negri E, Marubini E,
Dilling H, Mombour W, Schmidt M (2000) Internationale Ferraroni M, Gerber M, Richardson S, Segala C, Gatei D, Kenya
Klassifikation psychischer Störungen: ICD-10, Kapitel V (F) P, Kungu A, Mati JG, Brinton LA, Hoover R, Schairer C, Spirtas
klinisch-diagnostische Leitlinien. Weltgesundheitsorganisation. R, Lee HP, Rookus MA, van Leeuwen FE, Schoenberg JA,
Huber: Bern. McCredie M, Gammon MD, Clarke EA, Jones L, Neil A, Vessey
Dilling H, Mombour W, Schmidt M (2014) International M, Yeates D, Appleby P, Banks E, Beral V, Bull D, Crossley B,
Statistical Classification of Diseases and Related Health Problems Goodill A, Green J, Hermon C, Key T, Langston N, Lewis C,
10th Revision (ICD-10), Chapter V Mental and behavioural Reeves G, Collins R, Doll R, Peto R, Mabuchi K, Preston D,
disorders. World Health Organization, 9th edn. Verlag Hans Hannaford P, Kay C, Rosero-Bixby L, Gao YT, Jin F, Yuan
Huber: Bern. J-M, Wei HY, Yun T, Zhiheng C, Berry G, Cooper Booth J,
Dinh-Zarr T, Goss C, Heitman E, Roberts I, DiGuiseppi C (2004) Jelihovsky T, MacLennan R, Shearman R, Wang Q-S, Baines
Interventions for preventing injuries in problem drinkers. C-J, Miller AB, Wall C, Lund E, Stalsberg H, Shu XO, Zheng
Cochrane Database Syst Rev CD001857. W, Katsouyanni K, Trichopoulou A, Trichopoulos D,
Ewing JA (1984) Detecting alcoholism The CAGE questionnaire. Dabancens A, Martinez L, Molina R, Salas O, Alexander FE,
JAMA 252:1905–1907. Anderson K, Folsom AR, Hulka BS, Bernstein L, Enger S, Haile
Fitzgerald JL, Mulford HA (1985) An experimental test of tele- RW, Paganini-Hill A, Pike MC, Ross RK, Ursin G, Yu MC,
phone aftercare contacts with alcoholics. J Stud Alcohol Longnecker MP, Newcomb P, Kalache A, Farley TMM, Holck
46:418–424. S, Meirik O (2002) Alcohol, tobacco and breast cancer--
Fleming MF, Manwell LB, Barry KL, Adams W, Stauffacher EA collaborative reanalysis of individual data from 53 epidemio-
(1999) Brief physician advice for alcohol problems in older logical studies, including 58,515 women with breast cancer
adults: a randomized community-based trial. J Fam Pract and 95,067 women without the disease. Br J Cancer
48:378–384. 87:1234–1245.
Fleming MF, Mundt MP, French MT, Manwell LB, Stauffacher EA, Hanaoka T, Tsugane S, Ando N, Ishida K, Kakegawa T, Isono K,
Barry KL (2002) Brief physician advice for problem drinkers: Takiyama W, Takagi I, Ide H, Watanabe H (1994) Alcohol

consumption and risk of esophageal cancer in Japan: a case- Evaluating the effects of a brief motivational intervention for
control study in seven hospitals. Jpn J Clin Oncol 24:241–246. injured drinkers in the emergency department. J Stud Alcohol
Heather N, Campion PD, Neville RG, Maccabe D (1987) Evalua- 62:806–816.
tion of a controlled drinking minimal intervention for problem Longnecker MP (1994) Alcoholic beverage consumption in
drinkers in general practice (the DRAMS scheme). J R Coll Gen relation to risk of breast cancer: meta-analysis and review.
Pract 37:358–363. Cancer Causes Control 5:73–82.
Heinecke JW (2013) HDL’s protein cargo: friend or foe in Lönnroth K, Williams BG, Stadlin S, Jaramillo E, Dye C (2008)
cardioprotection? Circulation 127:868–869. Alcohol use as a risk factor for tuberculosis - a systematic
Howes LG (1985) Pressor effect of alcohol. Lancet (London, review. BMC Public Health 8:289.
England) 2:835. Magnus A, Cadilhac D, Sheppard L, Cumming T, Pearce D, Carter
Hsieh ST, Saito K, Miyajima T, Lin CM, Yokoyama M (1995) R (2012) The economic gains of achieving reduced alcohol
Effects of alcohol moderation on blood pressure and intracellu- consumption targets for Australia. Am. J. Public Health
lar cations in mild essential hypertension. Am J Hypertens 102:1313–1319.
8:696–703. Maheswaran R, Beevers M, Beevers DG (1992) Effectiveness of
Hulse GK, Tait RJ (2003) Five-year outcomes of a brief alcohol advice to reduce alcohol consumption in hypertensive
intervention for adult in-patients with psychiatric disorders. patients. Hypertension 19:79–84.
Addiction 98:1061–1068. Mann, K, Batra, A, Hoch, E, Reymann, G, Lorenz, G, Petersen, K,
IARC (2010) Alcohol Consumption and Ethyl Carbamate. IARC 2015. AWMF-076/001 “Screening, Diagnostik und
Monogr Eval Carcinog Risks Hum 96:3–1383. Behandlung alkoholbezogener Störungen”. Available at: http://
IARC (2012) Consumption of alcoholic beverages. IARC Monogr www.awmf.org/leitlinien/detail/ll/076-001.html. Accessed 02
Eval Carcinog Risks Hum 100E:1–128. June 2015
Joosten MM, Chiuve SE, Mukamal KJ, Hu FB, Hendriks HFJ, Mann K, Körkel J (2013) Trinkmengenreduktion: ein
Rimm EB (2011) Changes in alcohol consumption and ergänzendes Therapieziel bei Alkoholabhängigen?
subsequent risk of type 2 diabetes in men. Diabetes 60:74–79. Psychopharmakotherapie (Article in German) 20:193–198.
Kawano Y, Abe H, Takishita S, Omae T (1998) Effects of alcohol Mann K, Schäfer D, Längle G, Ackermann K, Croissant B (2005)
restriction on 24-hour ambulatory blood pressure in Japanese The long-term course of alcoholism, 5, 10 and 16 years after
men with hypertension. Am J Med 105:307–311. treatment. Addiction 100:797–805.
Koppes LLJ, Dekker JM, Hendriks HFJ, Bouter LM, Heine RJ Manwell LB, Fleming MF, Mundt MP, Stauffacher EA, Barry KL
(2005) Moderate alcohol consumption lowers the risk of type (2000) Treatment of problem alcohol use in women of
2 diabetes: a meta-analysis of prospective observational childbearing age: results of a brief intervention trial. Alcohol
studies. Diabetes Care 28:719–725. Clin Exp Res 24:1517–1524.
Kraemer KL, Maisto SA, Conigliaro J, McNeil M, Gordon AJ, Mathurin P, Hadengue A, Bataller R, Addolorato G, Burra P, Burt
Kelley ME (2002) Decreased alcohol consumption in outpa- A, Caballeria J, Cortez-Pinto H, Day C, Forrest E, Gual A, Leon
tient drinkers is associated with improved quality of life and D, Lligoña A, Jepsen P, Mueller S, Pageaux G, Roskams T, Seitz
fewer alcohol-related consequences. J Gen Intern Med H, Stickel F, Thursz M, Naveau S, Morgan T, Nevens F (2012)
17:382–386. EASL clinical practical guidelines: management of alcoholic
Kurz M (2012) Kapitel 3: Störungen durch psychotrope liver disease. J Hepatol 57:945–953.
Substanzen (ICD-10 F1). In: Fleischhacker WW, Hinterhuber McBride N, Farringdon F, Midford R, Meuleners L, Phillips M
H eds. Lehrbuch Psychiatrie, pp 51–110. Springer-Verlag: (2004) Harm minimization in school drug education: final
Wien. results of the School Health and Alcohol Harm Reduction
Kypri K, Hallett J, Howat P, McManus A, Maycock B, Bowe S, Project (SHAHRP). Addiction 99:278–291.
Horton NJ (2009) Randomized controlled trial of proactive McMurran M (1991) Young offenders and alcohol-related crime:
web-based alcohol screening and brief intervention for what interventions will address the issues? J Adolesc
university students. Arch Intern Med 169:1508–1514. 14:245–253.
Lang T, Nicaud V, Darné B, Rueff B (1995) Improving hyperten- Miller P, Plant M, Plant M (2005) Spreading out or concentrat-
sion control among excessive alcohol drinkers: a randomised ing weekly consumption: alcohol problems and other conse-
controlled trial in France. The WALPA Group. J Epidemiol quences within a UK population sample. Alcohol Alcohol
Community Health 49:610–616. 40:461–468.
Lieber CS (2003) Alcohol and health: a drink a day won’t keep Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred
the doctor away. Cleve Clin J Med 70:945–953. reporting items for systematic reviews and meta-analyses:
Lieber CS, Weiss DG, Groszmann R, Paronetto F, Schenker S the PRISMA statement. PLoS Med 6:e1000097.
(2003) II. Veterans Affairs Cooperative Study of Moreira MT, Smith LA, Foxcroft D (2009) Social norms interven-
polyenylphosphatidylcholine in alcoholic liver disease. Alcohol tions to reduce alcohol misuse in university or college
Clin Exp Res 27:1765–1772. students. Cochrane Database Syst Rev CD006748.
Little RE, Anderson KW, Ervin CH, Worthington-Roberts B, Mulford HA, Fitzgerald JL (1977) On the reliability of the
Clarren SK (1989) Maternal alcohol use during breast- Iowa Alcoholic Stages Index. J Stud Alcohol
feeding and infant mental and motor development at one year. 38:2197–2198.
N Engl J Med 321:425–430. Mundle G, Banger M, Mugele B, Stetter F, Soyka M, Veltrup C,
Liu S-I, Wu S-I, Chen S-C, Huang H-C, Sun F-J, Fang C-K, Hsu C- Schmidt L (2003) AWMF-Behandlungsleitlinien:
C, Huang C-R, Yeh H-M, Shih S-C (2011) Randomized Akutbehandlung alkoholbezogener Störungen. Sucht
controlled trial of a brief intervention for unhealthy alcohol 49:147–167.
use in hospitalized Taiwanese men. Addiction 106:928–940. National Health and Medical Reasearch Council (2001)
Longabaugh R, Woolard RE, Nirenberg TD, Minugh AP, Becker Australian Alcohol Guidelines: Health Risks and Benefits.
B, Clifford PR, Carty K, Licsw SF, Gogineni A (2001) Commonwealth of Australia: Canberra.

Newton NC, Vogl L, Teesson M, Andrews G (2011) Developing detection of persons with harmful alcohol consumption–II.
the climate schools: Alcohol and Cannabis Module: a harm- Addiction 88:791–804.
minimization, universal drug prevention program facilitated Scott E, Anderson P (1991) Randomized controlled trial of gen-
by the internet. Subst Use Misuse 46:1651–1663. eral practitioner intervention in women with excessive alcohol
Newton NC, Vogl LE, Teesson M, Andrews G (2009) CLIMATE consumption. Drug Alcohol Rev 10:313–321.
Schools: alcohol module: cross-validation of a school-based Seppä K, Laippala P, Sillanaukee P (1994) Drinking pattern and
prevention programme for alcohol misuse. Aust N Z J blood pressure. Am J Hypertens 7:249–254.
Psychiatry 43:201–217. Sesso HD, Stampfer MJ, Rosner B, Hennekens CH, Manson JE,
Nicolás JM, Fernández-Solà J, Estruch R, Paré JC, Sacanella E, Gaziano JM (2000) Seven-year changes in alcohol consump-
Urbano-Márquez A, Rubin E (2002) The effect of controlled tion and subsequent risk of cardiovascular disease in men.
drinking in alcoholic cardiomyopathy. Ann Intern Med Arch Intern Med 160:2605–2612.
136:192–200. Shaw GK, Waller S, Latham CJ, Dunn G, Thomson AD (1998)
Oesterle S, Hill KG, Hawkins JD, Guo J, Catalano RF, Abbott The detoxification experience of alcoholic in-patients and
RD (2004) Adolescent heavy episodic drinking trajectories predictors of outcome. Alcohol Alcohol 33:291–303.
and health in young adulthood. J Stud Alcohol Sitharthan T, Kavanagh DJ, Sayer G (1996) Moderating drinking
65:204–212. by correspondence: an evaluation of a new method of
Parker M, Puddey IB, Beilin LJ, Vandongen R (1990) Two-way intervention. Addiction 91:345–355.
factorial study of alcohol and salt restriction in treated hyper- Sitharthan T, Sitharthan G, Hough MJ, Kavanagh DJ (1997) Cue
tensive men. Hypertension 16:398–406. exposure in moderation drinking: a comparison with
Patra J, Bakker R, Irving H, Jaddoe VW, Malini S, Rehm J (2011) cognitive-behavior therapy. J Consult Clin Psychol
Dose-response relationship between alcohol consumption 65:878–882.
before and during pregnancy and the risks of low birthweight, Smith-Warner S, Spiegelman D, Yaun SS, van den Brandt P, Fol-
preterm birth and small for gestational age (SGA)-a systematic som A, Goldbohm R, Graham S, Holmberg L, Howe G, Mar-
review and meta-analyses. BJOG 118:1411–1421. shall J, Miller A, Potter J, Speizer F, Willett W, Wolk A,
Persson J, Magnusson PH (1989) Early intervention in patients Hunter D (1998) Alcohol and breast cancer in women: a
with excessive consumption of alcohol: a controlled study. pooled analysis of cohort studies. JAMA 279:535–540.
Alcohol 6:403–408. Sobell LC, Agrawal S, Sobell MB, Leo GI, Young LJ, Cunningham
Potamianos G, North WR, Meade TW, Townsend J, Peters TJ JA, Simco ER (2003) Comparison of a quick drinking screen
(1986) Randomised trial of community-based centre versus with the timeline followback for individuals with alcohol prob-
conventional hospital management in treatment of alcohol- lems. J Stud Alcohol 64:858–861.
ism. Lancet (London, England) 2:797–9. Sobell L, Sobell M (1995a) Alcohol Timeline Followback User’s
Puddey IB, Beilin LJ, Vandongen R, Rouse IL, Rogers P (1985) Manual. Addict Res Found.: Toronto.
Evidence for a direct effect of alcohol consumption on blood Sobell MB, Sobell LC (1995b) Controlled drinking after 25 years:
pressure in normotensive men. A randomized controlled trial. how important was the great debate? Addiction
Hypertension 7:707–713. 90:1149–1153; discussion 1157–77.
Puddey IB, Parker M, Beilin LJ, Vandongen R, Masarei JR (1992) Sokol RJ, Martier SS, Ager JW (1989) The T-ACE questions:
Effects of alcohol and caloric restrictions on blood pressure and practical prenatal detection of risk-drinking. Am J Obstet
serum lipids in overweight men. Hypertension 20:533–541. Gynecol 160:863–868; discussion 868–70.
Rakic V, Puddey IB, Burke V, Dimmitt SB, Beilin LJ (1998) Influ- Spanagel R, Durstewitz D, Hansson A, Heinz A, Kiefer F, Köhr G,
ence of pattern of alcohol intake on blood pressure in regular Matthäus F, Nöthen MM, Noori HR, Obermayer K, Rietschel
drinkers: a controlled trial. J Hypertens 16:165–174. M, Schloss P, Scholz H, Schumann G, Smolka M, Sommer W,
Rehm J, Patra J, Popova S (2007) Alcohol drinking cessation and Vengeliene V, Walter H, Wurst W, Zimmermann US, Stringer
its effect on esophageal and head and neck cancers: a pooled S, Smits Y, Derks EM (2013) A systems medicine research
analysis. Int J Cancer 121:1132–1137. approach for studying alcohol addiction. Addict Biol
Rehm J, Roerecke M (2013) Reduction of drinking in problem 18:883–896.
drinkers and all-cause mortality. Alcohol Alcohol Spitzer R, Williams J, Gibbon M, First M (1990) Structured Clinical
48:509–513. Interview for DSM-III-R. American Psychiatric Association
Rehm J, Zatonksi W, Taylor B, Anderson P (2011) Epidemiology Press: Washington, D.C.
and alcohol policy in Europe. Addiction 106:11–19. Stockwell T, Hodgson R, Edwards G, Taylor C, Rankin H (1979)
Robinson M, Oddy WH, McLean NJ, Jacoby P, Pennell CE, de The development of a questionnaire to measure severity of
Klerk NH, Zubrick SR, Stanley FJ, Newnham JP (2010) alcohol dependence. Br J Addict Alcohol Other Drugs
Low-moderate prenatal alcohol exposure and risk to child 74:79–87.
behavioural development: a prospective cohort study. BJOG Toth PP (2005) Cardiology patient page. The “good cholesterol”:
117:1139–1150. high-density lipoprotein. Circulation 111:e89–e91.
Roerecke M, Rehm J (2010) Irregular heavy drinking occasions Toumbourou JW, Beyers JM, Catalano RF, Hawkins JD, Arthur
and risk of ischemic heart disease: a systematic review and MW, Evans-Whipp T, Bond L, Patton GC (2005) Youth alcohol
meta-analysis. Am J Epidemiol 171:633–644. and other drug use in the United States and Australia: a
Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA (2011) cross-national comparison of three state-wide samples. Drug
Association of alcohol consumption with selected cardiovas- Alcohol Rev 24:515–523.
cular disease outcomes: a systematic review and meta- Ueshima H, Mikawa K, Baba S, Sasaki S, Ozawa H, Tsushima
analysis. BMJ 342:d671. M, Kawaguchi A, Omae T, Katayama Y, Kayamori Y
Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M (1993) Effect of reduced alcohol consumption on blood
(1993) Development of the Alcohol Use Disorders Identifica- pressure in untreated hypertensive men. Hypertension
tion Test (AUDIT): WHO collaborative project on early 21:248–252.

Vogl L, Teesson M, Andrews G, Bird K, Steadman B, Dillon P Witkiewitz K (2008) Lapses following alcohol treatment:
(2009) A computerized harm minimization prevention modeling the falls from the wagon. J Stud Alcohol Drugs
program for alcohol misuse and related harms: randomized 69:594–604.
controlled trial. Addiction 104:564–575. World Health Organization, 2014. Global status report on
Wachtel T, Staniford M (2010) The effectiveness of brief alcohol and health 2014.
interventions in the clinical setting in reducing alcohol misuse Xin X, He J, Frontini MG, Ogden LG, Motsamai OI, Whelton PK
and binge drinking in adolescents: a critical review of the (2001) Effects of alcohol reduction on blood pressure: a
literature. J Clin Nurs 19:605–620. meta-analysis of randomized controlled trials. Hypertension
Wallace P, Cutler S, Haines A (1988) Randomised controlled trial 38:1112–1117.
of general practitioner intervention in patients with excessive Yamada Y, Tsuritani I, Ishizaki M, Ikai E, Ishida M, Noborisaka Y,
alcohol consumption. BMJ 297:663–668. Honda R (1997) Serum gamma-glutamyl transferase levels
Wannamethee G, Shaper AG (1991) Alcohol intake and and blood pressure falls after alcohol moderation. Clin Exp
variations in blood pressure by day of examination. J Hum Hypertens 19:249–268.
Hypertens 5:59–67.
Wetterling T, Veltrup C, Driessen M, John U (1999) Drinking
pattern and alcohol-related medical disorders. Alcohol
Alcohol 34:330–336. SUPPORTING INFORMATION
Whelton PK, He J, Appel LJ, Cutler JA, Havas S, Kotchen TA,
Roccella EJ, Stout R, Vallbona C, Winston MC, Additional Supporting Information may be found in the
Karimbakas J (2002) Primary prevention of hyperten- online version of this article at the publisher’s web-site:
sion: clinical and public health advisory from The
National High Blood Pressure Education Program. JAMA
Appendix 1. Overview of the systematic literature
288:1882–1888.
research
Whitlock EP, Polen MR, Green CA, Orleans T, Klein J (2004)
Behavioral counseling interventions in primary care to reduce Table S1. Changes of biochemical markers together with
risky/harmful alcohol use by adults: a summary of the lowering blood pressure and alcohol reduction (values
evidence for the U.S. Preventive Services Task Force. Ann are only reported for experimental groups undergoing
Intern Med 140:557–568. alcohol limitation regimes)
WHO Brief Intervention Study Group (1996) A
Table S2. Overview of social norm intervention effects in
cross-national trial of brief interventions with heavy
drinkers. WHO Brief Intervention Study Group. Am J college- and university students (according to Moreira,
Public Health 86:948–955. Smith, & Foxcroft )
Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Hennekens CH, Supporting info item
Speizer FE (1987) Moderate Alcohol Consumption and the
Risk of Breast Cancer. N Engl J Med 316:1174–1180.

Harm Reduction-A Systematic Review On Effects of Alcohol Reduction On Physical and Mental Symptoms

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Harm Reduction-A Systematic Review On Effects of Alcohol Reduction On Physical and Mental Symptoms

Uploaded by

Copyright:

Available Formats

bs_bs_banner

ORIGINAL ARTICLE doi:10.1111/adb.12414

Harm reduction—a systematic review on effects of

INTRODUCTION inﬂuenced by diverse factors such as age, gender, familial

© 2016 Society for the Study of Addiction Addiction Biology

Table 1 Deﬁnition of hazardous, harmful alcohol consumption and alcohol dependence.

Hazardous alcohol consumption Harmful alcohol consumption Alcohol dependence syndrome

© 2016 Society for the Study of Addiction

alcohol-related problems (e.g. Wannamethee & Shaper METHODS

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction

2008 review and

© 2016 Society for the Study of Addiction

meta-analysis Quality of sleep

© 2016 Society for the Study of Addiction

© 2016 Society for the Study of Addiction

© 2016 Society for the Study of Addiction

Uncontrolled drinking days interpersonal, social and

© 2016 Society for the Study of Addiction

Days prior to ﬁrst drink after

© 2016 Society for the Study of Addiction

© 2016 Society for the Study of Addiction

© 2016 Society for the Study of Addiction

consumed per week externalizing behavior)

Mann et al. Prospective 16 years 20–63 N = 96 alcohol-dependent Drinking patternk Hospitalization,

© 2016 Society for the Study of Addiction

chronic illnesses and use of

© 2016 Society for the Study of Addiction

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction

restriction also appears to be relevant: a long-term

instead of a temporary alcohol reduction is

analysis of Xin et al. (2001) was based on RCTs testing

on cardiovascular disease such as hypertension. Further-

more, although the meta-analyses did not ﬁnd any publi-

et al. 2001; Roerecke & Rehm 2010; Ronksley et al.

only one study providing validation of self-reports by fam-

the method of alcohol assessment was lacking for three

et al. (2001) used self-reported alcohol measures, but no

one study (Nicolás et al. 2002) investigated the effects of

alcohol reduction on cardiological or cardiovascular dis-

1998; Sesso et al. 2000). Also, special cohorts such as

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology

© 2016 Society for the Study of Addiction Addiction Biology