Optimizing Protein Intake in Older Americans With Mobility Limitations

The recommended dietary allowance (RDA) for protein, set at 0.8 grams/kg/day for adult men
and women, has engendered debate and many experts advocate protein intakes substantially
above the RDA to help maintain muscle anabolism in older individuals. It is not known
whether increasing protein intake in older Americans, whose current intake is below the RDA,
increases skeletal muscle mass, muscle performance and physical function.

Our first aim is to determine whether administration of 1.3 g/kg/day of protein, compared to
the RDA (0.8 g/kg/day), will result in greater improvements in lean body mass, maximal
voluntary muscle strength and power, and self-reported and performance-based measures of
physical function in older men. Our second aim is to determine whether the gains in lean
body mass, maximal voluntary strength and self-reported and performance-based measures of
physical function during testosterone administration are greater with 1.3 g protein than
with the RDA in older men on a eucaloric diet.

We will conduct a randomized, placebo-controlled, double-blind trial using a 2 X 2 factorial
design. Community dwelling men, 65 years or older, who have self-reported mobility
limitation, a daily protein intake of <0.8 g/kg/day and no contraindications for
testosterone therapy, will be randomly assigned to one of four groups: placebo injections
plus protein 0.8 g/kg/day; placebo injections plus protein 1.3 g/kg/day; testosterone
enanthate 100 mg weekly plus protein 0.8 g/kg/day; testosterone enanthate 100 mg weekly plus
protein 1.3 g/kg/day. Treatment duration will be 6 months. The primary outcome is change in
lean body mass from baseline to 6 months, measured by dual energy X-ray absorptiometry.
Secondary outcomes include change in maximal voluntary strength in leg and chest press
exercises, leg power, self-reported (physical function domain of SF-36) and
performance-based measures of physical function (6-min walking distance and speed, stair
climbing power, and load carrying), fatigue, well-being and affectivity balance. Safety
measures include urinary calcium excretion, hematocrit, prostate specific antigen (PSA) and
prostate examination.

Inclusion Criteria:

1. Community-dwelling men 65 years of age or older

2. A score of 3-10 on the short physical performance battery (SPPB)

3. Daily protein intake less than the recommended daily allowance of 0.83 g/kg/day (from
3 24-hour food recalls)

4. Able to give informed consent

Exclusion Criteria:

1. History of prostate or breast cancer

2. American Urological Association [AUA] symptom index score of >19

3. Prostate specific antigen (PSA) >4 ng/ml in White men or >3 ng/ml in Black men

4. Prostate specific antigen (PSA) > 4 ng/ml in non-Black men or >3 ng/ml in Black men.
These subjects may be enrolled if they have a negative transrectal biopsy within the
past year.

5. Myocardial infarction or stroke within the last 6 months

6. Uncontrolled congestive heart failure, based on the study physician's evaluation

7. Serum creatinine > 2.0 mg/dL; men on any kind of dialysis will be excluded.

8. History of celiac disease, Crohn's disease, or ulcerative colitis

9. History of any malignancy requiring treatment within the previous 2 years, except
non-melanic skin cancers. Men with cancers who have not required active treatment
within the past two years and who have not had disease recurrence within the past two
years may be enrolled at the discretion of the study physician.

10. Neuromuscular diseases: motor neuron diseases, multiple sclerosis, adult muscular
dystrophies, and myasthenia gravis

11. History of stroke with residual limb weakness that affected the individual's ability
to walk; subjects with history of stroke who do not have residual limb weakness may
be enrolled.

12. Schizophrenia, bipolar disorder, or untreated diagnosed depression. Subjects with
unipolar depression who are on an antidepressant medication are eligible.

13. TSH levels <0.4 or >5 mlU/L

14. Systolic blood pressure (BP) >160 or diastolic BP >100 mm Hg (average of 2
measurements taken at Visit 1)

15. Hemoglobin A1c >8.0% or taking insulin. Men with diabetes mellitus whose A1C is less
than 8.0% or who are not taking insulin will be eligible.

16. Mini-Mental Status Exam [MMSE] <24

17. Body mass index (BMI) less than 20 or greater than 40 kg/m2

18. Not willing to eat all of the following: red meat, eggs, poultry, fish and shellfish

19. Allergy to sesame, peanuts, soy, gluten or shellfish

20. Current alcohol use >21 drinks/week based on self-report

21. Confinement to a wheelchair

22. Use of anabolic therapies (Testosterone, DHEA, androstenedione, rhGH) within the past
year

23. Current use of levodopa or anticoagulants

24. Current enrollment in a structured weight management program or participation in any
weight intervention studies in the last 90 days

25. Serum ALT and AST greater than 3 x upper limit of normal

26. Hematocrit < 30% or >48%

27. Subject is not able to eat 3 frozen study meals per day for 6 months

28. Subject is unwilling to stop current nutritional supplements

29. Progressive intensive resistance training within 12 weeks of screening

30. Non-compliant with run-in diet and/or supplement