Effect of alcohol consumption on systemic markers of inflammation

doi:10.1016/S0140-6736(00)04170-2

The Lancet

Volume 357, Issue 9258, 10 March 2001, Pages 763-767

https://doi.org/10.1016/S0140-6736(00)04170-2 Get rights and content

Summary

Background

Epidemiological studies suggest that light to moderate alcohol intake is associated with lower all-cause mortality than abstention or heavy alcohol intake, primarily through reduced risk of coronary heart disease. The underlying mechanisms are incompletely understood.

Methods

We investigated the association between alcohol consumption (assessed by a 7-day food record) and concentrations of C-reactive protein (CRP), al-globulins, a2-globulins, albumin, and transferrin, and leucocyte count in a sample of 2006 men and women aged 18–88 years participating in a national health survey carried out in former West Germany in 1987–88. Analyses were based on 781 men and 995 women with complete data.

Findings

Among men, alcohol consumption showed a U-shaped association with mean values of CRP (p for linear term 0·65, for quadratic term 0·048), α1-globulins (p=0·20, 0·0006), α2-globulins (p=0·82, 0·31), and leucocyte count (p=0·51, 0·26) even after adjustment for age, smoking, body-mass index, HDL and LDL cholesterol, history of hypertension, education, and income. There were inverted U-shaped associations between the negative acute-phase reactants albumin (p=0·41, 0·006) and transferrin (p=0·14, 0·28) and alcohol intake. In women, the associations were less strong for CRP (p=0·35, 0·31), leucocyte count (p=0·28, 0·15), and transferrin (p=0·86, 0·83). Concentrations of al-globulins and α2-globulins were inversely related to alcohol consumption, and albumin showed a positive association with increasing alcohol intake in women.

Interpretation

Non-drinkers and heavy drinkers had higher CRP concentrations than moderate drinkers. In view of the robust association between markers of inflammation, especially CRP, and risk of coronary heart disease, an anti-inflammatory action of alcohol could contribute to the link between moderate consumption and lower cardiovascular mortality.

Introduction

In epidemiological studies, consumers of moderate amounts of alcohol have lower all-cause mortality than non-drinkers and heavy drinkers.1, 2, 3, 4 There is general agreement that this U-shaped relation is due primarily to a lower risk of coronary heart disease.1, 2, 3, 4, 5, 6, 7 The alcohol intake at which all-cause mortality and risk of coronary heart disease are lowest remains unclear and seems to vary between men and women and among countries.2, 5, 6 Several mechanisms have been suggested by which alcohol intake could lower risk of coronary heart disease. Besides changes in lipoproteins such as increasing HDL cholesterol and apolipoprotein A1, several studies have shown an association between alcohol intake and a favourable haemostatic profile.⁸ Mennen and colleagues found a U-shaped association between alcohol consumption and fibrinogen concentrations in a large cross-sectional study.⁹ However, the available data suggest that there are also likely to be other mechanisms.

There is increasing evidence that atherosclerosis is an inflammatory disease.¹⁰ Inflammatory cells, including macrophages and T cells, are prominent in the atherothrombotic plaque.¹¹ The total leucocyte count and the concentration of fibrinogen, a haemostatic protein but also an acute-phase reactant, are independent risk factors for coronary heart disease and myocardial infarction.¹² Moreover, strong associations between concentrations of C-reactive protein (CRP), the classic marker of the acute-phase response, and risk of coronary events have been reported in several prospective population-based studies in apparently healthy people, as well as in patients with manifest atherosclerotic disease.¹³ In addition, low concentrations of serum albumin, a negative marker of the acute-phase response, have consistently been associated with risk of death from any cause and with cardiovascular mortality.¹² Even in patients presenting with unstable angina, CRP measured on admission was predictive of worse outcome both in hospital¹⁴ and in the long term.¹⁵

We have investigated the association between average daily alcohol intake and concentrations of CRP and other positive and negative markers of systemic inflammation in a large population-based sample of adults representative of the former West Germany.

Section snippets

Study design and population

This study is based on a national health and nutrition survey carried out in former West Germany in 1987–88 (Verbundstudie Ernährungserhebung und Risikofaktoren Analytik).¹⁶ A multistage, stratified probability sample was drawn from the population of German nationality aged 18–89 years, with exclusion of people living in institutions. 2006 men and women were recruited, with a participation rate of about 70%. The analyses presented are based on individuals with complete data for all variables

Results

About 6% of men and 13% of women did not consume any alcohol within the recorded 7-day period. A higher proportion of men than women were current smokers, whereas a higher proportion of women had never smoked (table 1). Women had lower mean body-mass index than men and were less likely to report a history of hypertension. Concentrations of α1-globulins, α2-globulins, transferrin, HDL cholesterol, and LDL cholesterol were higher in women than men, whereas those of albumin,

Discussion

Several prospective studies have found that light to moderate intake of alcoholic beverages was associated with lower all-cause mortality than abstention or heavy intake;1, 2, 3, 4, 5, 18 the lower all-cause mortality at moderate alcohol intake seems to be due primarily to a lower risk of coronary heart disease. The relation between alcohol consumption and incident coronary heart disease has been described as L-shaped in some studies1, 2, 3, 19 and as U-shaped in others.4, 20, 21 In the

References (28)

JM Gaziano et al.
Light-to-moderate alcohol consumption and mortality in the Physicians' Health Study enrollment cohort
J Am Coll Cardiol
(2000)
IR White
The level of alcohol consumption at which all-cause mortality is least
J Clin Epidemiol
(1999)
AG Shaper et al.
Alcohol and mortality in British men: explaining the U-shaped curve
Lancet
(1988)
J Muntwyler et al.
Mortality and light to moderate alcohol consumption after myocardial infarction
Lancet
(1998)
MF McCarty
Interleukin-6 as a central mediator of cardiovascular risk associated with chronic inflammation, smoking, diabetes, and visceral obesity: down-regulation with essential fatty acids, ethanol and pentoxifylline
Med Hypotheses
(1999)
H Baumann et al.
The acute phase response
Immunol Today
(1994)
U Keil et al.
The relation of alcohol intake to coronary heart disease and all-cause mortality in a beer-drinking population
Epidemiology
(1997)
CS Fuchs et al.
Alcohol consumption and mortality among women [published erratum N Engl J Med 1997; 336: 523]
N Engl J Med
(1995)
R Doll et al.
Mortality in relation to consumption of alcohol: 13 years' observations on male British doctors
BMJ
(1994)
P McElduff et al.
How much alcohol and how often? Population based case-control of alcohol consumption and risk of a major coronary event
BMJ
(1997)

A Romelsjo et al.

Association between alcohol consumption and mortality, myocardial infarction, and stroke in 25 year follow up of 49 618 young Swedish men

BMJ

(1999)

EB Rimm et al.

Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors

BMJ

(1999)

LI Mennen et al.

Fibrinogen: a possible link between alcohol consumption and cardiovascular disease? DESIR Study Group

Arterioscler Thromb Vasc Biol

(1999)

R Ross

Atherosclerosis–an inflammtory disease

N Engl J Med

(1999)

Cited by (476)

Effects of moderate ethanol exposure on risk factors for cardiovascular disease and colorectal cancer in adult Wistar rats
2024, Alcohol
While past studies have provided evidence linking excessive alcohol consumption to increased risk for cardiovascular diseases (CVDs) and colorectal cancer (CRC), existing data on the effects of moderate alcohol use on these conditions have produced mixed results. The purpose of this study was to investigate the effects of moderate alcohol consumption on risk factors associated with the development of CVDs and CRC in adult rats. Twenty-four, 14-month-old, non-deprived male Wistar rats were randomly assigned to either an ethanol group, which consisted of voluntary access to a 20% (v/v) ethanol solution on alternate days, or a water control group (n = 12/group) for 13 weeks. Blood samples were collected to analyze levels of albumin, glucose, adiponectin, lipids, oxidized low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (apoA1), C-reactive protein (CRP), high-mobility group box 1 protein (HMGB-1), tumor necrosis factor-alpha (TNF-α), thyroxine, thyroid-stimulating hormone, 8-oxo-2′-deoxyguanosine (8-oxo-dG), liver function enzymes, and antioxidant capacity. Colonic gene expression related to colon carcinogenesis was also assessed. Ethanol-treated rats were found to have significantly higher HDL-C and apoA1 levels compared to controls. Moderate alcohol consumption led to significantly lower CRP levels and a trend for decrease in HMGB-1, TNF-α, and 8-oxo-dG levels. In the ethanol-exposed group, colonic gene expression of superoxide dismutase was upregulated while aldehyde dehydrogenase 2 showed a trend for increase compared to the control group. These results indicate that adopting a moderate approach to alcohol consumption could potentially improve health biomarkers related to CVD and CRC by increasing HDL-C levels and antioxidant activity and reducing DNA damage and inflammatory activity.
Associations between perceived discrimination and immune cell composition in the Jackson Heart Study
2022, Brain, Behavior, and Immunity
African American adults suffer disproportionately from several non-communicable and infectious diseases. Among numerous contributing factors, perceived discrimination is considered a stressor for members of historically marginalized groups that contributes to health risk, although biological pathways are incompletely understood. Previous studies have reported associations between stress and both an up-regulation of non-specific (innate) inflammation and down-regulation of specific (adaptive) immunity. While associations between perceived discrimination and markers of inflammation have been explored, it is unclear if this is part of an overall shift that also includes down-regulated adaptive immunity. Relying on a large cross-section of African American adults (n = 3,319) from the Jackson Heart Study (JHS) in Jackson, Mississippi, we tested whether perceived everyday and lifetime discrimination as well as perceived burden from lifetime discrimination were associated with counts of neutrophils (innate), monocytes (innate), lymphocytes (adaptive), and the neutrophil-to-lymphocyte ratio (NLR), derived from complete white blood cell counts with differential. In addition, DNA methylation (DNAm) was measured on the EPIC array in a sub-sample (n = 1,023) of participants, allowing estimation of CD4T, CD8T and B lymphocyte proportions. Unexpectedly, high lifetime discrimination compared to low was significantly associated with lower neutrophils (b : -0.14, [95% CI: -0.24, -0.04]) and a lower NLR (b : -0.15, [95% CI: -0.25, -0.05]) after controlling for confounders. However, high perceived burden from lifetime discrimination was significantly associated with higher neutrophils (b : 0.17, [95% CI: 0.05, 0.30]) and a higher NLR (b : 0.16, [95% CI: 0.03, 0.29]). High perceived burden was also associated with lower lymphocytes among older men, which our analysis suggested might have been attributable to differences in CD4T cells. These findings highlight immune function as a potentially important pathway linking perceived discrimination to health outcomes.
Effects of Maternal Psychological Stress During Pregnancy on Offspring Brain Development: Considering the Role of Inflammation and Potential for Preventive Intervention
2022, Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Heightened psychological stress during pregnancy has repeatedly been associated with increased risk for development of behavior problems and psychiatric disorders in offspring. This review covers a rapidly growing body of research with the potential to advance a mechanistic understanding of these associations grounded in knowledge about maternal-placental-fetal stress biology and fetal brain development. Specifically, we highlight research employing magnetic resonance imaging to examine the infant brain soon after birth in relation to maternal psychological stress during pregnancy. This approach increases capacity to identify specific alterations in brain structure and function and to differentiate between effects of pre- versus postnatal exposures. We then focus on the extensive preclinical literature and emerging research in humans that have found that heightened maternal inflammation during pregnancy as a mechanism through which maternal stress influences the developing fetal brain. We place these findings in the context of recent work identifying psychotherapeutic interventions that have been found to be effective for reducing psychological stress among pregnant individuals and that also show promise for reducing inflammation. We argue that a focus on inflammation, among other mechanistic pathways, may lead to a productive and necessary integration of research focused on the effects of maternal psychological stress on offspring brain development and on prevention and intervention studies aimed at reducing maternal psychological stress during pregnancy. In addition to increasing capacity for common measurements and understanding potential mechanisms of action relevant to maternal mental health and fetal neurodevelopment, this focus may inform and broaden thinking about prevention and intervention strategies.
The inflammatory food index and its association with weight gain and incidence of diabetes: Longitudinal Study of Adult Health (ELSA-Brasil)
2022, Nutrition, Metabolism and Cardiovascular Diseases
Diet plays a central role in regulating inflammation and is closely related to the development of chronic diseases. We aimed to develop an inflammatory food index (IFI) based on the relationship of food items with biomarkers of inflammation and to evaluate its association with weight gain and type 2 diabetes.
A sample of 9909 participants of the ELSA-Brasil study was analyzed. Standardized measurements including interviews, anthropometry, and laboratory exams were performed at baseline and follow-up. A baseline food frequency questionnaire was used to derive IFI scores using reduced rank regression (RRR). The inflammatory pattern derived included 11 pro-inflammatory food groups: processed meat, red meat, pork, sugary soda, and hot dogs. The anti-inflammatory pattern included seven food groups: fruits, nuts, and wine. The IFI score, adjusted through logistic regression for multiple sociodemographic, behavioral, and clinical covariates, including body mass index, predicted the development of a large weight gain (tertile 3 vs. 1: OR = 1.30; 95%CI 1.08–1.55). The score, adjusted for sociodemographic factors through proportional hazard models, predicted incident diabetes (tertile 3 vs. 1: HR = 1.26; 95%CI 1.04–1.52).
These findings support the hypothesis that subclinical inflammation caused by a pro-inflammatory food pattern, characterized mainly by greater ultra-processed food consumption, underlies weight gain and the development of type 2 diabetes.
This study was registered at clinicaltrials.com as NCT02320461.
Association between drinking status and risk of kidney stones among United States adults: NHANES 2007–2018
2024, BMC Public Health
Association between alcohol consumption and incidence of type 2 diabetes in middle-aged Japanese: Panasonic cohort study 12
2024, Research Square

View all citing articles on Scopus

View full text

Early ReportEffect of alcohol consumption on systemic markers of inflammation

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Study design and population

Results

Discussion

J Am Coll Cardiol

J Clin Epidemiol

Lancet

Lancet

Med Hypotheses

Immunol Today

The relation of alcohol intake to coronary heart disease and all-cause mortality in a beer-drinking population

Epidemiology

Alcohol consumption and mortality among women [published erratum N Engl J Med 1997; 336: 523]

N Engl J Med

Mortality in relation to consumption of alcohol: 13 years' observations on male British doctors

BMJ

How much alcohol and how often? Population based case-control of alcohol consumption and risk of a major coronary event

BMJ

Association between alcohol consumption and mortality, myocardial infarction, and stroke in 25 year follow up of 49 618 young Swedish men

BMJ

Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors

BMJ

Fibrinogen: a possible link between alcohol consumption and cardiovascular disease? DESIR Study Group

Arterioscler Thromb Vasc Biol

Atherosclerosis–an inflammtory disease

N Engl J Med

Early Report
Effect of alcohol consumption on systemic markers of inflammation