Aging, Osteoporosis, Sarcopenia
Conditions
Brief summary
The purpose of this study is to determine if taking the pain reliever acetaminophen (ACET) interferes with some of the benefits of weight lifting on muscles and bone density in older men.
Detailed description
The commonly used pain relievers acetaminophen and ibuprofen may impair musculoskeletal adaptations to progressive resistance exercise training by inhibiting exercise-induced muscle protein synthesis. To test the hypothesis that acetaminophen and ibuprofen would diminish training-induced increases in fat-free mass, untrained men (n=26) aged ≥ 50 years participated in 16 weeks of high-intensity progressive resistance exercise training and bone-loading exercises and were randomly assigned to take ACET (1000 mg), ibuprofen (400 mg) or placebo 2 hours before each exercise session. The primary outcome was the change in total body fat-free mass measured by dual-energy X-ray absorptiometry (DXA) at baseline and week 16. Our primary interest was in the comparison of the acetaminophen and placebo groups.
Interventions
BEHAVIORALResistance training
high intensity progressive resistance exercise training
Sponsors
National Institute on Aging (NIA)
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* average use of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) \[including aspirin\] less than 3 days per month * not currently engaged in moderate-to-vigorous weight-lifting exercise * non-smoker * willing to participate in a supervised exercise program for 9 months
Exclusion criteria
* relative or absolute contraindications to regular use of acetaminophen or NSAIDs including known allergy or intolerance to either drug,history of peptic ulcer or GI bleeding, anemia, asthma with bronchospasm induced by aspirin or other NSAIDS, moderate or severe renal impairment, known hepatobiliary disease * contraindications to exercise testing and training including congestive heart failure class III or IV, uncontrolled hypertension and unstable cardiovascular disease * thyroid dysfunction * orthopedic problems that limit the ability to perform vigorous exercise or increase the likelihood of the use of pain medications * drugs known to alter bone metabolism * allergy to lidocaine * diabetes mellitus requiring pharmacologic therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Body Fat-free Mass | 16 weeks | change from baseline to 16 weeks in fat-free mass measured by DXA (Hologic Discovery W, version 12.6) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Body Fat Mass | 16 weeks | Change from baseline to 16 weeks in total body fat mass. |
| Changes in Upper Body Strength. | 16 weeks | Strength was measured using the one-repetition maximum method. Upper body strength was a composite of bench press, overhead press, seated row, and lateral pull-down strength. |
| Change in Lower Body Strength | 16 weeks | Strength was measured using the one-repetition maximum method. Lower body strength was a composite of knee flexion, knee extension, and leg press strength. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled from Dec 2006 to Jan 2010. They were recruited from the greater Denver area using advertisements.
Pre-assignment details
Volunteers who did not meet inclusion criteria were excluded from the study during the initial screening visits prior to randomization to the study arms.
Participants by arm
| Arm | Count |
|---|---|
| Acetaminophen and Resistance Exercise Progressive resistance exercise training and bone-loading exercise on up to 6 days per week and administration of acetaminophen, 1000 mg, taken 2 hours before exercise on exercise days for up to 36 weeks. | 13 |
| Ibuprofen and Resistance Exercise Progressive resistance exercise training and bone-loading exercise on up to 6 days per week and administration of acetaminophen, 400 mg, taken 2 hours before exercise on exercise days for up to 36 weeks. | 8 |
| Placebo and Resistance Exercise Progressive resistance exercise training and bone-loading exercise on up to 6 days per week and placebo pills (matching active study drug) taken 2 hours before exercise on exercise days for up to 36 weeks. | 13 |
| Total | 34 |
Baseline characteristics
| Characteristic | Acetaminophen and Resistance Exercise | Ibuprofen and Resistance Exercise | Placebo and Resistance Exercise | Total |
|---|---|---|---|---|
| Age Continuous United States | 63 years STANDARD_DEVIATION 5 | 58 years STANDARD_DEVIATION 6 | 62 years STANDARD_DEVIATION 7 | 61 years STANDARD_DEVIATION 6 |
| Fat-free mass | 65.2 kg STANDARD_DEVIATION 6.1 | 63.5 kg STANDARD_DEVIATION 8.2 | 62.7 kg STANDARD_DEVIATION 9.1 | 63.4 kg STANDARD_DEVIATION 8 |
| Fat mass | 29.3 kg STANDARD_DEVIATION 12.6 | 25.8 kg STANDARD_DEVIATION 5.3 | 25.2 kg STANDARD_DEVIATION 9.6 | 27.0 kg STANDARD_DEVIATION 10 |
| Height | 181 cm STANDARD_DEVIATION 8 | 178 cm STANDARD_DEVIATION 10 | 176 cm STANDARD_DEVIATION 7 | 178 cm STANDARD_DEVIATION 6.4 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 13 Participants | 8 Participants | 13 Participants | 34 Participants |
| Weight | 94.5 kg STANDARD_DEVIATION 16.6 | 89.3 kg STANDARD_DEVIATION 12.5 | 87.9 kg STANDARD_DEVIATION 18 | 90.4 kg STANDARD_DEVIATION 16.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 13 | 0 / 8 | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 8 | 0 / 13 |
Outcome results
Primary
Change in Total Body Fat-free Mass
change from baseline to 16 weeks in fat-free mass measured by DXA (Hologic Discovery W, version 12.6)
Time frame: 16 weeks
Population: All participants with baseline and 16 week data were included in the analysis (i.e., intention-to-treat).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetaminophen and Resistance Exercise Training | Change in Total Body Fat-free Mass | 1.5 kg | Standard Error 0.6 |
| Ibuprofen and Resistance Exercise Training | Change in Total Body Fat-free Mass | 2.3 kg | Standard Error 0.9 |
| Placebo and Resistance Exercise Training | Change in Total Body Fat-free Mass | 0.7 kg | Standard Error 0.6 |
Comparison: The null hypothesis was that the changes in total body fat-free mass in response to resistance exercise training would not be different among the groups. The expected difference in fat-free mass between the Acetaminophen and Placebo groups was 1.8 +/- 1.0% with a 3.6 +/1 1.0% increase in fat-free mass in the Placebo group. The study was designed to achieve 96% power at the 0.05 level with 10 men in the acetaminophen and placebo groups.p-value: 0.38ANCOVA
Secondary
Change in Lower Body Strength
Strength was measured using the one-repetition maximum method. Lower body strength was a composite of knee flexion, knee extension, and leg press strength.
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetaminophen and Resistance Exercise Training | Change in Lower Body Strength | 33.1 lbs | Standard Error 9.4 |
| Ibuprofen and Resistance Exercise Training | Change in Lower Body Strength | 40.8 lbs | Standard Error 14.6 |
| Placebo and Resistance Exercise Training | Change in Lower Body Strength | 18.0 lbs | Standard Error 9.8 |
p-value: 0.37ANCOVA
Secondary
Change in Total Body Fat Mass
Change from baseline to 16 weeks in total body fat mass.
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetaminophen and Resistance Exercise Training | Change in Total Body Fat Mass | -1.5 kg | Standard Error 0.6 |
| Ibuprofen and Resistance Exercise Training | Change in Total Body Fat Mass | -1.4 kg | Standard Error 0.9 |
| Placebo and Resistance Exercise Training | Change in Total Body Fat Mass | -0.2 kg | Standard Error 0.6 |
p-value: 0.23ANCOVA
Secondary
Changes in Upper Body Strength.
Strength was measured using the one-repetition maximum method. Upper body strength was a composite of bench press, overhead press, seated row, and lateral pull-down strength.
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetaminophen and Resistance Exercise Training | Changes in Upper Body Strength. | 19.5 lbs | Standard Error 5.5 |
| Ibuprofen and Resistance Exercise Training | Changes in Upper Body Strength. | 35.2 lbs | Standard Error 8.6 |
| Placebo and Resistance Exercise Training | Changes in Upper Body Strength. | 26.5 lbs | Standard Error 5.8 |
p-value: 0.3ANCOVA