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Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

Aims

  1. To investigate resting and postprandial EE and fuel utilization in individuals abusing alcohol chronically, before and after abstention from alcohol.

Definitions

  • Steady state: Not discussed
  • 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: mean values for t=100 min to t=220
Inclusion Criteria:
  1. Understand and give written consent
  2. For alcohol (AA) group: referred to an outpatient facility for assessment of chronic alcohol abuse and were actively abusing alcohol at the time of assessment.
  3. Healthy controls: selected as gender-, age- (±7 y), and weight (±5 kg) matched controls for individuals in the AA group.
Exclusion Criteria:

AA excluded if:

  1. Refusal to consent
  2. Gave a history of physical dependence on alcohol
  3. Had symptoms or signs of acute alcohol withdrawal
  4. Had decompensated liver disease
  5. Taking medications known to affect metabolic homeostasis
  6. Was a known drug abuser
  7. Had active or past infection with hepatitis B, hepatitis C, or human immunodeficiency virus
  8. Had diabetes mellitus
  9. Exercised more than twice per week
  10. Reported a change (5%) in body weight in the 6 mos. prior to the study
  11. Showed clinical signs of malabsorption
  12. Refused admission to hospital for detoxification and full assessment to include liver biopsy.

Healthy controls excluded if:

  1. Had a history of clinical or biochemical evidence of chronic liver disease
  2. Had a history of chronic alcohol misuse or abuse
  3. Currently drank alcohol in excess of 5g daily
  4. Exercised more than twice per week
  5. Reported a change (5%) in body weight in the prior 6 m
  6. Used any medication
  7. Showed clinical evidence of malabsorption
  8. Had acute or chronic disease

Patients in AA group underwent initial evaluation as outpatients on the day before the study with complete history including nutritional, psychiatric, and social history. Physical exam was performed.
Description of Study Protocol:

ANTHROPOMETRIC

  • Ht measured? Yes; using standard protocol
  • Wt measured? Yes, using standard protocol
  • Fat-free mass measured? Yes
  • Skinfold thicknesses were measured in quadruplicate, at the triceps, biceps, subscapular and suprailiac sites.

CLINICAL

  • Monitored heart rate? Not mentioned
  • Body temperature? Not mentioned
  • Medications administered? No

Resting energy expenditure

  • IC type: Indirect, flow-over hood calorimeter
  • Equipment of Calibration: At the beginning of each assessment and 2-hourly thereafter
  • Coefficient of variation using std 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: 2 hr before initial measurement
  • Measurement length: Resting=50 min; after meal 150 min continuously; 2-min period both resting and after meal
  • Measurement duration: 150 minutes
  • Steady state: Not mentioned
  • Fasting length: Abstain from food and beverage/alcohol consumption from 22:00 h the evening prior to testing; abstinence from alcohol confirmed by determining zero breath alcohol.
  • Exercise restrictions: Not discussed
  • Room temp: Thermal
  • No. of measures within the measurement period: Initial for 50 min and after meal for 150 min
  • Were some measures eliminated? No
  • Were a set of measurements averaged?
    1. Resting EE and resting NPRQ were defined as the mean values for t=20 min to t=50 min, respectively.
    2. Postprandial EE and postprandial NPRQ were defined as the mean values for t=100 min to t=220.
  • Coefficient of variation in subjects’ measures? CV for repeat measures of REE and resting NPRQ was <1% (subjects)
  • Training of measurer? Performed by the same experienced observer
  • Subject training of measuring process? Not mentioned

DIETARY

Duplicate assessments of habitual dietary intake; Provided with a standard food meal of 29·9 MJ (7·14 kcal)/kg body weight which comprised 12% protein, 33% fat, and 55% carbohydrate; Meal time was limited to 20 min (t=51 min to t=70 min).

AA group:hospitalized for a minimum of 10 days; provided with oral fluids and diet w/minimum of 8·4 MJ day –1 and 70 g day-1 of protein.

  • Intervening factor: 42% of the AA group were habitual cigarette smokers; Four (11%) of control were habitual cigarette smokers.
Data Collection Summary:

Outcome(s) and other measures

  1. RMR, RQ, resting NPRQ, Postprandial EE and postprandial NPRQ
  2. Urine collected to complete the 6-h urine collection that was analyzed for nitrogen
  3. Ht, wt, BMI, skinfold thicknesses MAMC.
  4. Dietary intake assessment.
  5. Patients in the AA group: liver biopsy and venous blood studies were performed.
  6. Resting EE and were defined as the mean values for t=20 min to t=50 min, respectively.
  7. Were defined as the mean values for t=100 min to t=220.

Blinding used: No

Description of Actual Data Sample:

Alcoholic

  • N=36 AA; 20 M; 16 F
  • Mean age, (SEM), y: 42±2 yr

Control

  • N=36; 20 M; 16 F
  • Mean age, (SEM), y: 43±2 y

[Subjects matched by gender-, age- (±7 yr) and weight (±5 kg) matched to AA individuals]

Statistical tests

Within and between group comparisons were made using Student’s paired and unpaired t-tests. ANOVA was applied where appropriate and post hoc t-testing was performed. Sign was defined as p<0.05.

Summary of Results:

ANTHROPOMETRIC

AA Group Mean±SE Range
Wt, kg 67.2±2

BMI, kg/m2

23±1

Fat-free body mass (kg)

53±2
Fat mass, (%) 21
MAMC (cm) 23±0.4

Alcohol abuse (yrs)

13±2

 1-30 yrs

Alcohol use (g/d)

181±14

 52-400 g

Control Group

Mean±

Wt, kg

68±2

BMI

24±1

Fat-free body mass

52±2

Fat mass

22±1

MAMC

23±0.6

MEASUREMENT PROCESS

  • Number of measurements: Initial for 50 min and after meal for 150 min (continuous)
  • Length of measurements: Resting=50 min; after meal 150 min continuously; oxygen consumption and carbon dioxide production calculated for each 2-min period both resting and after meal.

MEASUREMENT TIMING

  • Sleep or rest: Subjects rested for 2 h prior to initial measurement
  • Physical activity: Not discussed; but states subjects were sedentary (exercised no more than twice a week)

INDIVIDUAL CHARACTERISTICS

  • Dietary intakes of protein, fat, carbohydrate and total non-alcohol energy intakes were similar in 2 groups. However, when the energy intake from alcohol was included, the difference in total energy intake between the 2 groups was significant (15±1 cf. 9±1 MJ) (p<0.001).
  • Mean resting EE was sign greater in the AA group compared to the control group (p<0.001) and when expressed relative to body weight (p<0.001) or fat-free mass (p<0.001)
  • Mean resting NPRQ was decreased in the AA group, 0·75±0·02, compared to control subjects, 0·82±0·01 (p<0.001)

THERMIC RESPONSE TO FOOD

After the standard meal, the increase in postprandial EE was not sign 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.

Post-prandial AUC

  • Alcoholic: 25.1±2.8 kcal
  • Controls: 25.8±4.8
  • Similarly, the change in NPRQ after the standard meal was similar in the AA group compared to the healthy controls.

SMOKING DATA

Data for the AA subjects were compared based on smoking behavior. EE was not sign greater in those who smoked and 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).

Author Conclusion:

“We found, however, that alcoholic patients consumed alcohol in addition to normal food intake. Furthermore, resting EE was markedly increased in alcoholic patients compared to matched healthy controls and this effect 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.”

“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."

“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."

“An unexpected finding was that smoking blunted the metabolic responses to feeding such that the meal was not associated with the anticipated increase in RQ."

“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.”
Funding Source:
University/Hospital: Mayo Clinic, Royal Free Hospital and School of Medicine (London, UK)
Reviewer Comments:

Note:  This quality rating is different than that assigned for the same study when answering the alcohol evidence analysis question. This is due to a research design designation, because this evidence analysis question is different than researcher plan.

Strengths

  • Good description of study protocol and accuracy of IC measurements.
  • Anthropometric measurements performed by one trained individual to minimize variability between observers.

Limitations

  • Small sample sizes; possible type 2 error
  • Generalizability: sample consisted of non-obese, middle-aged, sedentary individuals; controls were selected from individuals attending a health screening program (selection bias; these individuals may not representative of population as 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
Relevance Questions
  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
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? N/A
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? N/A
  1.3. Were the target population and setting specified? N/A
2. Was the selection of study subjects/patients free from bias? Yes
  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? N/A
  2.2. Were criteria applied equally to all study groups? N/A
  2.3. Were health, demographics, and other characteristics of subjects described? N/A
  2.4. Were the subjects/patients a representative sample of the relevant population? N/A
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  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? Yes
  4.1. Were follow-up methods described and the same for all groups? N/A
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  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? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  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? N/A
  7.2. Were nutrition measures appropriate to question and outcomes of concern? N/A
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? N/A
  7.5. Was the measurement of effect at an appropriate level of precision? N/A
  7.6. Were other factors accounted for (measured) that could affect outcomes? N/A
  7.7. Were the measurements conducted consistently across groups? N/A
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? No
  8.1. Were statistical analyses adequately described and the results reported appropriately? N/A
  8.2. Were correct statistical tests used and assumptions of test not violated? N/A
  8.3. Were statistics reported with levels of significance and/or confidence intervals? N/A
  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)? N/A
  8.6. Was clinical significance as well as statistical significance reported? N/A
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? No
  9.1. Is there a discussion of findings? N/A
  9.2. Are biases and study limitations identified and discussed? N/A
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? N/A
  10.2. Was the study free from apparent conflict of interest? N/A