Context Epidemiologic data demonstrate that moderate alcohol intake is associated
with improved insulin sensitivity in nondiabetic individuals. No controlled-diet
studies have addressed the effects of daily moderate alcohol consumption on
fasting insulin and glucose concentrations and insulin sensitivity.
Objective To determine whether daily consumption of low to moderate amounts of
alcohol influences fasting insulin and glucose concentrations and insulin
sensitivity in nondiabetic postmenopausal women.
Design, Setting, and Participants Randomized controlled crossover trial of 63 healthy postmenopausal women,
conducted at a clinical research center in Maryland between 1998 and 1999.
Interventions Participants were randomly assigned to consume 0, 15, or 30 g/d of alcohol
for 8 weeks each as part of a controlled diet. All foods and beverages were
provided during the intervention. An isocaloric beverage was provided in the
0-g/d arm. Energy intake was adjusted to maintain constant body weight.
Main Outcome Measures Fasting insulin, triglyceride, and glucose concentrations, measured
at the end of each dietary period; insulin sensitivity, estimated with a published
index of glucose disposal rate corrected for fat-free mass based on fasting
insulin and fasting triglyceride concentrations, compared among treatments
with a mixed-model analysis of variance.
Results A complete set of plasma samples was collected and analyzed for 51 women
who completed all diet treatments. Consumption of 30 g/d of alcohol compared
with 0 g/d reduced fasting insulin concentration by 19.2% (P = .004) and triglyceride concentration by 10.3% (P = .001), and increased insulin sensitivity by 7.2% (P = .002). Normal-weight, overweight, and obese individuals responded
similarly. Only fasting triglyceride concentration was significantly reduced
when comparing 0 and 15 g/d of alcohol (7.8%; P =
.03), and no difference was found between consumption of 15 and 30 g/d of
alcohol; however, there was a significant linear trend (P = .001). Fasting glucose concentrations were not different across
Conclusions Consumption of 30 g/d of alcohol (2 drinks per day) has beneficial effects
on insulin and triglyceride concentrations and insulin sensitivity in nondiabetic
Moderate alcohol intake has been shown to be cardioprotective. Hyperinsulinemia
and reduced insulin sensitivity are risk factors for cardiovascular disease
and type 2 diabetes mellitus1-4
and appear to be influenced by alcohol intake. Alcohol intake (1-2 drinks
per day) is associated with reduced risk for type 2 diabetes, reduced fasting
insulin concentration, and/or improved insulin sensitivity.5-9
Furthermore, menopause is associated with increased risk for cardiovascular
disease,10,11 increased prevalence
of hyperinsulinemia, and reduced insulin sensitivity.12,13
Therefore, we evaluated whether daily consumption of low to moderate amounts
of alcohol influences insulin and glucose concentration and insulin sensitivity
in postmenopausal women who consumed controlled diets.
Postmenopausal women participated in a study conducted at the Beltsville
Human Nutrition Research Center (Beltsville, Md) from 1998 through 1999 with
primary objectives of evaluating the effect of daily moderate alcohol consumption
on risk for cancer and cardiovascular disease.14,15
Eligibility criteria were no history of alcoholism by the woman or her parents,
at least 50 years old, postmenopausal (last menses at least 1 year earlier
and follicle-stimulating hormone concentration >0.04 IU/L), not using hormone
replacement therapy, 90% to 140% of ideal weight, no signs of major health
problems, and not taking medications that could interfere with carbohydrate
or lipid metabolism. The study was approved by the institutional review boards
of the National Cancer Institute and Johns Hopkins University School of Hygiene
and Public Health. All volunteers provided informed consent and received base
compensation of $3000.
A total of 63 women were randomized and initiated the study, and 53
completed the study (Figure 1).
The sample size was based on the anticipated need to detect the effect of
alcohol on estradiol and dehydroepiandrosterone. Women consumed either 15
g/d of alcohol (1 drink), 30 g/d of alcohol (2 drinks), or an isocaloric beverage
(0 g/d alcohol) as part of a controlled diet in a randomized crossover design
for 8 weeks per diet treatment. Each period was preceded by a 2- to 5-week
washout period. Random allocation to treatment sequence and washout periods
were used to eliminate carryover from previous treatment. All foods and beverages
were prepared and supplied by the Center's Human Studies Facility. Menus were
prepared to provide 54% of calories from carbohydrates or carbohydrates and
alcohol, 32% from fat, and 14% from protein. Alcohol was supplied as ethanol
(Everclear, Daniel Sherman Corp, St Louis, Mo) in orange juice (340 mL). Energy
from alcohol was replaced with energy from carbohydrates (Polycose, Ross Products
Division, Columbus, Ohio) and soft drinks. Vitamin and mineral supplementation
was not permitted. Energy intake was adjusted to maintain constant weight.
Volunteers were not informed of the alcohol content of the beverages and were
instructed to consume study beverages at home, at least 1 to 2 hours before
bedtime, after completing tasks requiring substantial dexterity.
Blood was collected after an overnight fast on 3 separate days at the
end of each dietary period. An equal volume of serum from each day was pooled
for analyses. Glucose concentration was measured enzymatically (Sigma, St
Louis, Mo) and insulin concentration was measured by an enzyme-linked immunosorbent
assay (Diagnostic Systems Laboratories Inc, Webster, Tex). Fasting triglyceride
concentration was determined enzymatically.15
Insulin sensitivity was estimated with a recently published index (MFFM) that
was developed using regression analysis to determine predictors of glucose
disposal rates (M) corrected for fat-free mass (FFM) from hyperinsulinemic-euglycemic
clamp test.16 This index was developed as a
surrogate for the labor-intensive and time-intensive methods for assessing
insulin sensitivity, the hyperinsulinemic-euglycemic clamp, and frequently
sampled intravenous glucose tolerance tests. With this index, a weighted combination
of log-transformed fasting insulin and triglyceride concentration is shown
to predict insulin sensitivity in normoglycemic men and women.16
Statistical analyses were performed using SAS version 8.02 (SAS Institute,
Cary, NC). Individuals were stratified by body mass index (BMI) according
to clinically relevant cutpoints: normal weight (n = 17, BMI <25 kg/m2), overweight (n = 21, BMI ≥25 kg/m2 and BMI ≤30 kg/m2), and obese (n = 13, BMI >30 kg/m2). Insulin, glucose,
triglyceride concentration, and MFFM were compared between treatments with
a mixed analysis of variance model that included fixed terms for diet, BMI
stratum, period, patient (repeated term), and a diet by BMI stratum interaction.
Of the 53 women who completed the study, we report data for 51 (1 woman
was an outlier based on plasma triglyceride concentration and 1 woman had
incomplete data). Baseline characteristics are presented in Table 1. Weight remained constant across treatments (overall mean
[SEM], 73.6 [1.3] kg). No adverse events associated with alcohol consumption
Diet composition and intake were previously published.15
Daily caloric intake was similar with 0, 15, and 30 g/d of alcohol included
in the diet (mean [SEM], 2378 , 2381 , and 2361  kcal/d, respectively).
Daily alcohol intake was 4.5% (range, 3.5%-5.3%) of caloric intake for 15
g/d of alcohol and 9.0% (range, 6.9%-10.6%) for 30 g/d of alcohol. By design,
total carbohydrate intake (315.1 [4.6], 281.6 [4.5], and 249.1 [4.0] g/d)
was reduced with increasing alcohol intake. Energy from carbohydrates decreased
from 53% with 0 g/d of alcohol to 47.3% with 15 g/d of alcohol to 42.2% with
30 g/d of alcohol with fat (energy, 32%-34%) and protein (energy, 15%) fixed.
Fasting insulin concentration was reduced by 19.2% (P = .004) after consumption of 30 g/d of alcohol compared with 0 g/d
(Table 2) with no change in glucose
concentration. When women consumed 30 g/d of alcohol compared with 0 g/d,
there was a significant improvement of 7.2% in insulin sensitivity (P = .002), as estimated by MFFM. Fasting triglyceride concentrations
were previously reported to be significantly reduced with alcohol consumption
(7.8% [P = .03] after consumption of 15 g/d of alcohol and 10.3% [P = .001]
after consumption of 30 g/d of alcohol) (Table 2).15 Fasting insulin concentration
and insulin sensitivity were not significantly changed with intake of 15 g/d
of alcohol compared with 0 g/d or 30 g/d of alcohol diet (Table 2). Although BMI influences fasting insulin and glucose concentrations
and insulin sensitivity, there was no significant interaction between BMI
stratification and treatment. Thus, the effect of alcohol on fasting insulin
and triglyceride concentration and insulin sensitivity was similar with respect
to magnitude and direction for all BMI strata (P
This study is the first to our knowledge to demonstrate that fasting
insulin concentration is reduced with daily moderate alcohol intake (30 g/d
of alcohol or 2 drinks per day) compared with a placebo drink in postmenopausal
women. Given the source of alcohol (ethanol) used and the careful control
of other dietary factors, the response can be attributed to the ethanol. It
is unknown if alcohol derived from other sources (eg, beverages that contain
sugar) may impart the same response. We also evaluated the association between
alcohol intake and fasting insulin concentration for clinically relevant strata
of BMI. We found that fasting insulin concentration remained lower when consuming
30 g/d of alcohol compared with 0 g/d within each BMI stratum. Although weight
gain can influence fasting insulin,17 weight
was constant across diet treatments.
Alcohol consumption influences insulin sensitivity (or insulin resistance),
as assessed by different methods.5-7,9,18,19
The MFFM index includes fasting insulin and triglyceride concentration, both
independent risk factors for type 2 diabetes and cardiovascular disease.1 Fasting triglyceride concentration was reduced by
approximately 10% when comparing 30 g/d of alcohol with 0 g/d.15
Insulin sensitivity was enhanced after consumption of 30 g/d alcohol compared
with 0 g/d, independent of BMI, which confirms the findings of recent cross-sectional
These results do not support those who report that the protective effect of
alcohol intake on insulin sensitivity is diminished after adjusting for differences
in body composition.20
No changes in insulin concentration and insulin sensitivity were found
when these women consumed 15 g/d of alcohol compared with a placebo beverage.
These findings are consistent with the results of Cordain et al21
and with epidemiologic data.22-24
Moreover, the relative risk for developing type 2 diabetes is significantly
reduced in women who consume more than 15 g/d of alcohol (≥1 alcoholic
drinks per day) compared with nondrinkers.5
The significant linear effect indicates that this study population may have
been too small to detect the small changes between 0 g/d and 15 g/d of alcohol
relative to the SE. Although the effect of alcohol is linear within the range
of BMI for volunteers in the study cohort, it is unknown if the response to
alcohol remains linear for women with a BMI greater than those in the study
In the present study, energy from alcohol was replaced with energy from
carbohydrates (Polycose and soft drinks). Although low-fat, high-carbohydrate
diets influence plasma triglyceride concentration,25
there are conflicting reports on the effects of increasing dietary carbohydrates
on fasting insulin concentration and insulin sensitivity.26
Moreover, most study designs involving changes in dietary carbohydrates include
concomitant changes in dietary fat, which also influence fasting insulin concentration
and insulin sensitivity.27-32
These studies demonstrate the complex nature of interpreting results from
studies involving macronutrient manipulation. Most studies alter energy from
carbohydrate by nearly 20% for comparisons between diets. In the present study,
energy from carbohydrates increased from 42.2% to 53.0% when comparing the
30 g/d of alcohol diet with the 0 g/d alcohol diet. Since the difference in
carbohydrate energy between treatments was well below those reported by others,30-32 the observed insulin
changes were likely related to alcohol intake and not alterations in dietary
In conclusion, consumption of 30 g/d of alcohol reduced insulin concentration
and improved insulin sensitivity in nondiabetic, postmenopausal women independent
of BMI. The observed effects are attributed to ethanol, though other components
in red wine may impart additional cardioprotective effects.33
Elevated fasting insulin concentration is associated with increased insulin
resistance,4 which is a shared pathology in
the degenerative diseases, type 2 diabetes and cardiovascular disease.34 The observed changes with alcohol intake may reduce
the risk of developing type 2 diabetes and cardiovascular disease in this
population of women. In addition to these potentially beneficial changes in
insulin sensitivity, an improved lipid profile is reported in this cohort
of women while consuming 2 drinks per day compared with the placebo treatment.
However, in contrast to these potentially beneficial findings, alcohol intake
(1-2 drinks per day) in this cohort significantly increased serum levels of
dehydroepiandrosterone sulfate and estrone sulfate compared with the placebo.14 These steroid hormones are risk factors for breast
cancer.35 While the magnitude of the effect
of alcohol on risk for cardiovascular disease in this group of women can be
estimated,15 it is more difficult to assess
the relative effect on risk for breast cancer or diabetes. These data might
prove helpful when counseling women on alcohol consumption.
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