Influence of Age and Sex on Alcohol Metabolism and Acute Responses
This study will examine age and sex differences in alcohol metabolism and the effects of alcohol. Men and women differ in their ability to metabolize alcohol, possibly due to differences between men and women in lean body mass, liver size, or the activity of enzymes that act on alcohol in the liver. Also, older men and women are thought to be more sensitive to alcohol, although the reasons for this are not clear.
Healthy men and women between 21 and 25 years of age and between 55 and 65 years of age who are social drinkers may be eligible for this study. Candidates will be screened with questionnaires about their general and mental health, alcohol use, and family history of alcohol use and problems. They will have a physical examination, electrocardiogram (EKG), routine blood tests, urinalysis to test for drugs of abuse, and a blood test to study the gene responsible for enzymes that metabolize alcohol. Younger women will have a urine pregnancy test and older women will have a test to confirm post-menopausal status.
Participants will have two study sessions at the NIH Clinical Center outpatient clinic. They come to the clinic by taxi and, upon arrival, take a breathalyzer test for any measurable alcohol levels. They are then given breakfast, after which two catheters (plastic tubes) are placed, one in a vein in each arm. One tube is used to collect blood samples for measuring hormone levels; the other is for infusing alcohol. The infusion is adjusted so that the breath alcohol level is held constant for about 3 hours at a moderate level. Baseline measurements are taken before the infusion begins. During and after the infusion, the participants fill out questionnaires about their moods and feelings. Breath alcohol level and heart rate measurements are monitored frequently. After the test, participants remain in the clinic until their breath alcohol level drops below 0.02 g/L (generally 2 to 3 hours after the infusion stops). They are given lunch and then sent home in a taxi.
Participants also undergo a dual energy x-ray absorptiometry (DEXA) scan to determine lean body mass and a magnetic resonance imaging (MRI) scan of the abdomen to determine liver size. For the DEXA scan, the subject lies still on a table for about 30 minutes while the whole body is scanned using a small amount of radiation. For the MRI, the subject lies in a narrow metal cylinder (the scanner) about 30 minutes for the scan.
|Official Title:||Influence of Age and Sex on Alcohol Metabolism and Acute Responses|
|Study Start Date:||September 2003|
|Estimated Study Completion Date:||May 2011|
Previous studies, including our studies using the alcohol clamp, have shown that alcohol pharmacokinetics differ between women and men. Some of the factors that may contribute to these sex differences in absorption, distribution and metabolism include variation in lean body mass (and total body water), liver size and differences in activity or capacity of alcohol metabolizing enzymes in the stomach and livers of women and men. A fundamental difference between men and women is in the levels of the sex hormones estrogen and testosterone, which can influence several of the above factors. Sex differences in alcohol pharmacokinetics, and estrogen itself, have been postulated as determinants of the increased susceptibility of women to alcohol-related liver disease. An additional area of interest is sex- and age-related differences in sensitivity to the effects of alcohol. The elderly are thought to be more sensitive to alcohol and show greater impairment than younger individuals. However, it is not clear if these changes are due to pharmacokinetic or pharmacodynamic factors.
The objectives of this project are (I) to evaluate the influence of age and sex on alcohol elimination rates in men and women, and (II) to determine the influence of age and sex on the initial response and acute adaptation to alcohol on measures of subjective perceptions of alcohol effects and heart rate. This study will be conducted in 24 young and 24 older participants, with equal numbers of males and females in each group. Comparison of alcohol elimination rates across these groups and correlation with liver volume and sex steroid levels will provide a means to examine the influence of sex hormones, estrogen and testosterone, in age-related and sex-related differences in alcohol metabolism and liver volume. This study will examine age- and sex- related differences in response to alcohol on subjective measures of intoxication and mood, as well as on heart-rate and psychophysiological responses to emotional visual stimuli (pictures). This study will also evaluate the effect of acute alcohol administration on gene expression in peripheral blood cells. Findings from these studies will provide important new data regarding the role of sex steroids (estrogen and testosterone) on the metabolism of alcohol, and a better understanding of age- and sex-related differences in metabolic processes that may underlie medically important differences in the responses of individuals to alcohol.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|