Utilizing Protein During Weight Loss to Impact Physical Function

The study will use a 3-group design in 225 obese (BMI 27-45 kg/m2), older (65-85 years) men
and women at risk for disability (eSPPB <2.5) who will undergo a 6-month weight loss
intervention followed by a 12-month follow-up phase to test the overall hypothesis that a
higher protein (1.2 g/kg body wt/d) / lower carbohydrate (CHO) diet during a 6-month weight
loss intervention improves physical function compared with an isocaloric lower protein (the
current Recommended Dietary Allowance (RDA), 0.8 g/kg body wt/d) / higher CHO diet, and
whether continuing a higher protein / lower CHO diet for 12-months following weight loss will
result in better maintenance of improved physical function. All participants will undergo a
6-month weight loss intervention involving caloric restriction and supervised exercise
followed by 12 months of follow-up with randomization to one of three groups (n=75/group): 1)
Lower protein / higher CHO diet for the 6-month weight loss phase only (RecProt); 2) Higher
protein / lower CHO diet for the 6-month weight loss phase only (6-mo HiProt); or 3) Higher
protein / lower CHO diet for the 6-month weight loss and 12-month follow-up phases (18-mo
HiProt). Physical function (primary aim) will be assessed by the expanded Short Physical
Performance Battery (primary outcome) and lower extremity muscle strength at baseline, 6-,
12- and 18-months. Weight loss maintenance and body composition (secondary aim) will be
assessed by dual-energy X-ray absorptiometry (DXA) and computed tomography (CT) at baseline,
6- and 18-months. Bone mineral density (DXA) and cardiometabolic risk factors will also be
measured at baseline, 6- and 18-months.

Inclusion Criteria:

- 65-85 years

- BMI: 27-45 kg/m2

- No regular resistance training and/or aerobic exercise (>20 mins/d) for past 6 months

- eSPPB <2.5

- No contraindications for safe and optimal participation in exercise training

- Approved for participation by Medical Director (Dr. Lyles)

- Willing to provide informed consent

- Agree to all study procedures and assessments

- Willing to consume protein/CHO supplements for up to 18 months

- Able to provide own transportation to study visits and intervention sessions

Exclusion Criteria:

- Weight loss (≥5%) in past 6 months

- Dependent on cane or walker

- Cognitive impairment (MoCA score <22)

- Severe arthritis, or other musculoskeletal disorder

- Joint replacement or other orthopedic surgery in past 6 months

- Uncontrolled resting hypertension (>160/90 mmHg);

- Insulin-dependent or uncontrolled diabetes (HbA1c ≥8%)

- Current or recent past (within 1 year) severe symptomatic heart disease, uncontrolled
angina, stroke, chronic respiratory disease requiring oxygen; uncontrolled
endocrine/metabolic disease; neurological or hematological disease; cancer requiring
treatment in past year, except non-melanoma skin cancers; liver or renal disease; or
clinically evident edema

- Unstable, severe depression

- Serious conduction disorder, uncontrolled arrhythmia, or new Q waves or ST-segment
depressions (>3 mm at rest or ≥2 mm with exercise)

- Abnormal kidney function (eGFR <30 based on serum creatinine, age, gender, and race)

- Anemia (Hb<13 g/dL in men; <12 g/dL in women)

- Drug abuse or excessive alcohol use (>7 drinks/week women; >14 drinks/week men)

- Use of any tobacco or nicotine products in the past year

- Osteoporosis (T-score < -2.5 on hip or spine scan)

- Regular use of growth/steroid hormones, sex steroids or corticosteroids, osteoporosis
medication, or protein supplements

- Weight loss medications or procedures

- Current participation in another intervention study