EE: Thermic Effect of Food (2014)
Levine JA, Harris MM, Morgan MY. Energy expenditure in chronic alcohol abuse. Eur J Clin Invest 2000; 39: 779-786.PubMed ID: 10198077
To investigate resting and postprandial EE and fuel utilization in individuals abusing alcohol chronically, before and after abstention from alcohol.
- Give informed consent
- Alcohol abuse (AA) group: Referred to an outpatient facility for assessment of chronic alcohol abuse and were actively abusing alcohol at the time of assessment
- Healthy controls: Selected as gender, age (±7 years), and weight (±5kg) matched controls for individuals in the AA group.
- Gave a history of physical dependence on alcohol
- Had symptoms or signs of acute alcohol withdrawal
- Had decompensated liver disease
- Taking medications known to affect metabolic homeostasis
- Were a known drug abuser
- Had active or past infection with hepatitis B, hepatitis C, or human immunodeficiency virus
- Had diabetes mellitus
- Exercised more than twice per week
- Reported a change (5%) in body weight in the six months prior to the study
- Showed clinical signs of malabsorption
- Refused admission to hospital for detoxification and full assessment to include liver biopsy.
Healthy Controls Exclusions
- Had a history of clinical or biochemical evidence of chronic liver disease
- Had a history of chronic alcohol misuse or abuse
- Currently drank alcohol in excess of 5g daily
- Exercised more than twice per week
- Reported a change (5%) in body weight in the prior six months
- Used any medication
- Showed clinical evidence of malabsorption
- Had acute or chronic disease.
- Alcohol abuse group: Comprised of adults referred to an outpatient facility for assessment of chronic alcohol abuse
- Healthy controls: Selected from adults attending a health screening program
Before-after study with matched controls
- Areas under the curves for postprandial EE were calculated: The coefficient of variation for repeat measures of resting EE and resting NPRQ in human subjects was <1% and for comparisons with butane standard, 0.5%
- Within and between group comparisons were made using Student's paired and unpaired T-tests
- Analysis of variance (ANOVA) was applied where appropriate
- Post-hoc T-testing was applied where appropriate.
Timing of Measurements
- AA group underwent initial evaluation as outpatients on the day before the study
- At this time, a complete history was obtained (detailed alcohol use and abuse, physical dependence to alcohol or previous symptomatic alcohol withdrawal, and nutritional, psychiatric and social history).
- Physical exam was performed
- Patients who remained at the hospital were re-evaluated after 14 days or on days 2, 4, 6, 8, 14 and 42 after alcohol abstinence.
- Healthy controls underwent a similar evaluation on the day before the study (one testing day only).
- Both AA and controls were transported to the metabolic suite at 6:00 a.m. on the first day of the study
- Bladder evacuated for measurement of six-hour urine
- T=1 to T=50 minutes: Resting EE and RQ measured
- T=51 to T=71 minutes: Meal provided (standard food meal of 29.9MJ (7.14 kcal) per kg body weight, which comprised 12% protein, 33% fat and 55% carbohydrate, and requested to eat all food provided)
- T=71 to T=220 minutes: Postprandial EE and RQ measured
- T=200 to T=240 minutes: Rest and evacuation of bladder for six-hour urine collection
- Resting and postprandial energy expenditure (EE) and respiratory quotient (RQ):
- IC type: Indirect, flow-over hood calorimeter
- Equipment of calibration: At the beginning of each assessment and two-hourly thereafter
- Coefficient of variation using standard gases: Yes (confirmed by chemical analyses); the coefficient of variation for repeat measures of resting EE and resting NPRQ was <1% (subjects) and for comparisons with a butane standard was 0.5%.
- Rest before measure: Two hours before initial measurement
- Measurement length: Resting=50 minutes; after meal 150 minutes continuously; oxygen consumption and carbon dioxide production calculated for each two-minute period both resting and after meal.
- Steady state: Not mentioned
- Fasting length: Abstain from food and beverage/alcohol consumption from 10:00 p.m. the evening prior to testing; abstinence from alcohol confirmed by determining zero breath alcohol.
- Exercise restrictions: Not discussed, but states subjects were sedentary (exercised no more than twice a week)
- Room temperature: Thermal
- Number of measures within the measurement period: Initial for 50 minutes and after meal for 150 minutes
- Were some measures eliminated? No
- Were a set of measurements averaged? Resting EE and resting NPRQ were defined as the mean values for T=20 min to T=50 min, respectively; postprandial EE and postprandial NPRQ were defined as the mean values for T=100 min to T=220.
- Coefficient of variation in subjects measures? The coefficient of variation for repeat measures of resting EE and resting NPRQ was <1% (subjects)
- Training of measurer? All anthropometric measurements were performed by the same experienced observer
- Subject training of measuring process? Not mentioned
- Monitored heart rate? Not mentioned
- Body temperature? Not mentioned
- Medications administered? No
Anthropometrics: Height, weight, BMI, skinfold thicknesses—triceps, biceps, subscapular and suprailiac sites and mid-arm circumference for MAMC.
Resting and postprandial nonprotein RQ (NPRQ): Six-hour urine collection analyzed for nitrogen.
- Abstinence from alcohol
- Patients in the AA group were then hospitalized for a minimum of 10 days during which a liver biopsy and venous blood studies were performed
- AA patients were provided with oral fluids and a diet containing a minimum of 8.4MJ day -1 and 70g day-1 of protein
- Alcohol abuse vs. no-alcohol (controls).
- Forty-two percent of the AA group were habitual cigarette smokers
- Four (11%) of the control were habitual cigarette smokers.
- Initial N: Not given
- Final N
- AA group: N=36; 20 males and 16 females
- Controls: N=36; 20 males and 16 females
- AA group: 42±2 years
- Controls: 43±2 years
- Ethnicity: Not specified
AA group (mean±SE)
Fat-free body mass (kg)
Fat mass (%)
Alcohol abuse (yrs)
13±2 (range one year to 30 years)
Alcohol use (g per day)
181±14 (range 52g to 400g) and all actively abusing alcohol at the time of recruitment
- Location: London, UK.
- Fifteen (42%) of AA subjects were habitual cigarette smokers
- Four (11%) of control were habitual cigarette smokers
- Liver biopsy demonstrated that 21 patients (58%) had fatty liver, eight (22%) had alcoholic hepatitis and seven (19%) had alcoholic cirrhosis; patients in the three histological subgroups did not differ significantly in mean age, weight, duration of drinking history or alcohol consumption.
- All patients in the AA group had consumed alcohol within 24 hours of the study but none within eight hours of study.
- Dietary intakes of protein, fat, carbohydrate and total non-alcohol energy intakes were similar in two groups; however, when the energy intake from alcohol was included, the difference in total energy intake between the two groups was significant [15±1MJ day -1 (38%±2% from alcohol) vs. 9±1MJ day -1] (360kcal vs. 216kcal per day) (P<0.001).
- The thermogenic response to food was similar in both groups. After the standard meal, the increase in postprandial EE was not significantly different in the AA group compared with the healthy control group, either when expressed as an absolute change in EE or as areas under the curve.
- Similarly, the change in NPRQ after the standard meal was similar in the AA group compared to the healthy controls.
Resting Energy Expenditure
- Mean resting EE was significantly greater (P<0.001) in the AA group (82±2W) compared to the control group (65±2W) and when expressed relative to body weight (AA vs. controls: 1.3±0.04W per kg) vs. 1.0±0.03W per kg, P<0.001) or fat-free mass (AA vs. controls: 1.6±0.06W per kg vs.1.3±0.04W per kg, P<0.001).
Postprandial Energy Expenditure
- Mean postprandial EE was significantly greater (P<0.001) in the AA group (93±3W) vs. controls (77±3W)
- However, the increase in postprandial EE was almost identical in both groups (AA vs. control: 11±2 vs. 11±1W, NS).
- Mean resting NPRQ was decreased in the AA group, 0.75±0.02, compared to control subjects, 0.82±0.01 (P<0.001)
- Mean postprandial NPRQ was decreased in the AA group, 0.82±0.03 compared to controls 0.89±0.01 (P<0.02)
- The change in NPRQ was not significantly different between AA and controls.
Alcohol Abuse Individuals and Smoking
- Resting EE was not significantly greater in those who smoked
- The change in EE after the meal was similar in smokers and nonsmokers
- The resting NPRQ was similar in the smokers, 0.74±0.02 compared with the nonsmokers, 0.77±0.02. However, the postprandial NPRQ was diminished in the smokers, 0.77±0.03 compared with the NPRQ nonsmokers, 0.87±0.03 (P<0.05) and the change after the meal was 0.03±0.02 for the smokers and 0.10±0.02 for the nonsmokers (P<0.05).
Comparisons in Those with Liver Injury
- Anthropometric variables and dietary intake were similar between the patient groups
- Patients with steatosis had greater resting EE expressed per kg fat-free mass, 1.7+0.1W per kg-1, compared with the combined group of the hepatitis and cirrhotic patients, 1.4+0.1W per kg-1 (P<0.02).
- Repeat measurements were carried out in 14 patients from the AA group, two weeks after abstinence from alcohol (steatosis N=9; hepatitis N=3; cirrhosis N=2; five were lost to repeated measures because of early symptoms of withdrawal)
- There was a significant decrease in total energy intake from 16±1MJ per day-1 (39+4% from alcohol) to 11±1MJ per day-1, P<0.005)
- Body weight over this time remained unchanged 64±3kg vs. 75±3kg
- After 14 days of abstinence, mean resting EE decreased from 84±5W to 73±4W (P<0.05)
- Resting NPRQ and postprandial thermogenesis were unchanged
- There were no differences between patients with different liver disease histological subtypes after abstinence
- Serial measurements were obtained in six patients on Days 0, 2, 4, 6, 14 and 42 after abstinence from alcohol; there was a constant decrease in resting EE in all the subjects between two and four days after abstinence from alcohol (P<0.05).
When healthy subjects consume ethanol in addition to normal food intake, lipid oxidation decreases so that adipose tissue accumulation is favored. However, individuals who chronically abuse alcohol are not obese.
We found that alcoholic patients consumed alcohol in addition to normal food intake [and] resting EE was markedly increased in alcoholic patients compared to matched healthy controls. [The REE increase] was reversed within a week of discontinuing alcohol.
Also, alcohol abuse was accompanied by decreased RQ, suggesting that net substrate utilization favored a lipid-rich metabolic mixture and lipid oxidation, which is in direct contrast to when healthy individuals consume excess ethanol. Thus, chronic alcohol abuse is not only associated with energy wasting but also with impaired adipose tissue accumulation. This may explain why alcoholics are not obese despite high total energy intakes.
It was originally thought that individuals abusing alcohol replaced food calories with alcohol, but more recent studies have demonstrated that alcoholics consume alcohol in addition to food intake and data from the present study support these observations. Our food intake data should be interpreted cautiously however, because of the inherent limitations of retrospective food intake determination.
Resting EE was markedly increased in the alcohol patients we studied even when corrected for lean body mass. The magnitude of the increase in resting EE (26%) is sufficient to effect energy balance and body weight substantially since resting EE accounts for two-thirds of total EE in sedentary individuals. The pivotal role of alcohol is further supported by the consistent reversal of the stimulation of resting EE within days of abstinence from alcohol.”
The effect of chronic alcohol abuse on resting EE appears to be specific. Meal-induced thermogenesis was unaltered in the alcoholic patients we studied, although our postprandial measurement period was limited, to a degree, by the constraints of providing care for alcoholic patients recently discontinuing alcohol. We did not measure exercise-induced thermogenesis in our patients; whether nonexercise, activity-related thermogenesis is increased in alcoholics remains undetermined. Thus, resistance of chronic alcohol abusers to obesity, despite high energy intake appears, at least in part, related to specific increases in resting EE.
More of the subjects we studied smoked compared to the healthy controls. Since cigarette smoking is associated with small increases in EE, it is possible that smoking might have accounted for some of the increase in EE; although it certainly did not account for the majority of the difference...smoking blunted the metabolic responses to feeding such that the meal was not associated with the anticipated increase in RQ. This might reflect the increased insulin resistance seen in smokers accompanied by the impaired glycogen utilization.
In conclusion, chronic alcohol abuse is associated with preservation of food intake, stimulation of resting EE, suppression of glycogen utilization and promotion of a lipid-rich metabolic mixture more reflective of lipolysis. It is likely that these factors contribute to the lack of obesity seen in alcoholics despite high energy intakes.
|University/Hospital:||Mayo Clinic, Royal Free Hospital and School of Medicine (London, UK)|
NOTE: This study has both a case-control comparison of resting and postprandial EE, RQ, NPRQ and a before-after comparison (before and after abstinence from alcohol). There are also repeated measures of these variables for a small subsample during the period of withdrawal from alcohol.
- Good description of study protocol and accuracy of IC measurements.
- Anthropometric measurements performed by one trained individual to minimize variability between observers.
- Small sample sizes; possible Type 2 error
- Sample consisted of nonobese, middle-aged, sedentary individuals; controls were selected from individuals attending a health screening program (selection bias: these individuals may not representative of population as they more likely to be more health conscious)
- Results may not be generalizable to obese, younger or older individuals
- Definition of sedentary: sedentary defined as not exercising more than twice a week; however the type of exercise was not defined (ex vigorous and high intensity exercise twice a week is different from leisure-time, low-intensity exercise)
- Inherent limitations of retrospective food intake measurements: Recall bias, under- or over-reporting intake; although assessments were duplicated, the correlation was not reported
- Loss to follow up with AA group (lost to repeated measures because of early symptoms of withdrawal or withdrawal from study)
- Although N=36 for AA and controls, anthropometric and laboratory variables were collected on 35 in each group (20 males and 15 females). Withdraw from study? Not explained in results.
Quality Criteria Checklist: Primary Research
|1.||Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)||Yes|
|2.||Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?||Yes|
|3.||Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?||Yes|
|4.||Is the intervention or procedure feasible? (NA for some epidemiological studies)||Yes|
|1.||Was the research question clearly stated?||Yes|
|1.1.||Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?||Yes|
|1.2.||Was (were) the outcome(s) [dependent variable(s)] clearly indicated?||Yes|
|1.3.||Were the target population and setting specified?||Yes|
|2.||Was the selection of study subjects/patients free from bias?||???|
|2.1.||Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?||Yes|
|2.2.||Were criteria applied equally to all study groups?||Yes|
|2.3.||Were health, demographics, and other characteristics of subjects described?||Yes|
|2.4.||Were the subjects/patients a representative sample of the relevant population?||???|
|3.||Were study groups comparable?||Yes|
|3.1.||Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)||Yes|
|3.2.||Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?||Yes|
|3.3.||Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)||Yes|
|3.4.||If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?||N/A|
|3.5.||If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)||N/A|
|3.6.||If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?||N/A|
|4.||Was method of handling withdrawals described?||No|
|4.1.||Were follow-up methods described and the same for all groups?||No|
|4.2.||Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)||No|
|4.3.||Were all enrolled subjects/patients (in the original sample) accounted for?||No|
|4.4.||Were reasons for withdrawals similar across groups?||N/A|
|4.5.||If diagnostic test, was decision to perform reference test not dependent on results of test under study?||N/A|
|5.||Was blinding used to prevent introduction of bias?||No|
|5.1.||In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?||N/A|
|5.2.||Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)||N/A|
|5.3.||In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?||N/A|
|5.4.||In case control study, was case definition explicit and case ascertainment not influenced by exposure status?||N/A|
|5.5.||In diagnostic study, were test results blinded to patient history and other test results?||N/A|
|6.||Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?||Yes|
|6.1.||In RCT or other intervention trial, were protocols described for all regimens studied?||N/A|
|6.2.||In observational study, were interventions, study settings, and clinicians/provider described?||Yes|
|6.3.||Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?||Yes|
|6.4.||Was the amount of exposure and, if relevant, subject/patient compliance measured?||Yes|
|6.5.||Were co-interventions (e.g., ancillary treatments, other therapies) described?||N/A|
|6.6.||Were extra or unplanned treatments described?||N/A|
|6.7.||Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?||N/A|
|6.8.||In diagnostic study, were details of test administration and replication sufficient?||N/A|
|7.||Were outcomes clearly defined and the measurements valid and reliable?||Yes|
|7.1.||Were primary and secondary endpoints described and relevant to the question?||Yes|
|7.2.||Were nutrition measures appropriate to question and outcomes of concern?||Yes|
|7.3.||Was the period of follow-up long enough for important outcome(s) to occur?||Yes|
|7.4.||Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?||Yes|
|7.5.||Was the measurement of effect at an appropriate level of precision?||???|
|7.6.||Were other factors accounted for (measured) that could affect outcomes?||Yes|
|7.7.||Were the measurements conducted consistently across groups?||Yes|
|8.||Was the statistical analysis appropriate for the study design and type of outcome indicators?||Yes|
|8.1.||Were statistical analyses adequately described and the results reported appropriately?||Yes|
|8.2.||Were correct statistical tests used and assumptions of test not violated?||Yes|
|8.3.||Were statistics reported with levels of significance and/or confidence intervals?||Yes|
|8.4.||Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?||N/A|
|8.5.||Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?||Yes|
|8.6.||Was clinical significance as well as statistical significance reported?||Yes|
|8.7.||If negative findings, was a power calculation reported to address type 2 error?||No|
|9.||Are conclusions supported by results with biases and limitations taken into consideration?||Yes|
|9.1.||Is there a discussion of findings?||Yes|
|9.2.||Are biases and study limitations identified and discussed?||Yes|
|10.||Is bias due to study's funding or sponsorship unlikely?||Yes|
|10.1.||Were sources of funding and investigators' affiliations described?||Yes|
|10.2.||Was the study free from apparent conflict of interest?||Yes|