Table 3.

Randomized controlled trials of combination therapy and sarcopenia.

Author	Population	Intervention	Results of Supplemental Protein + Vitamin D vs. Placebo	With Exercise?
Bauer 2015 [92]	n = 380 (297 completed), age ≥ 65 years, with class I or II sarcopenia.	20 g whey protein, 3 g leucine, 800 IU VitD supplement vs. isocaloric placebo supplement for 13 weeks.	Nonsignificant differential increase in SPPB performance and hand-grip strength in both groups. Significant increase in chair-stand test performance in experimental group vs. placebo group. Experimental group also gained more appendicular muscle mass than control.	No.
Rondanelli 2016 [93]	n = 130, age ≥ 65 years, relative muscle mass Z score ≤ 2.	Nutritional supplement: 22 g whey protein, 100 IU vitD. Groups: Supplement group vs. isocaloric placebo for 12 weeks.	Significant differential increase in fat-free mass, relative skeletal muscle mass, and hand-grip strength in the intervention group.	Yes, both groups received physical activity training.
Chanet 2017 [94]	n = 24, age ≥ 65 years, men with BMI between 20 and 30.	Nutritional supplement: 21 g leucine-enriched whey protein + 800 IU vitD3. Groups: Nutritional supplement vs. noncaloric placebo before breakfast for 6 weeks.	Significant differential improvement in mixed muscle protein fixed synthesis rate (FSR) as well as appendicular lean mass growth in the intervention group, mainly as lean leg mass.	No.
Abe 2016 [95]	n = 38, age ≥ 65 years, resided in nursing home and required special care from helper.	Nutritional supplement: L-leucine (1.2 g), vitD3 (20 ug). Groups: Leucine supplement (LD) + 6 g Medium Chain Triglycerides (MCTs) vs. Leucine supplement + 6 g Long Chain Triglycerides (LCTs) vs. isocaloric placebo for 3 months.	Significant differential improvement in bodyweight, grip strength, and walking speed in the LD + MCT group only.	No.
Malafarina 2017 [96]	n = 107 (92 completed), age ≥ 65, with hip fractures.	Nutritional supplement: Ensure® Plus Advance containing 20.02 g milk protein, Calcium β-hydroxy-β-methylbutyrate (CaHMB) 1.54 g, 499.4IU vitD, 499.4 mg Ca. Groups: Nutritional supplement group vs. control group (no placebo supplement) until discharge from rehabilitation center.	Significant differential in intervention group; appendicular lean mass and BMI were stable while in the control group, these factors decreased.	No, but patients were undergoing rehabilitation for hip fracture.
Kim 2016 [97]	n = 139, age ≥ 70 years, met criteria for sarcopenic obesity.	Nutritional supplement: EAA supplement + 20 ug vitD + tea fortified with 540 mg catechins. Groups: Exercise + nutrition vs. exercise alone vs. nutrition alone vs. health education group for 3 months.	Significant differential reduction in trunk fat and total body mass in thd Exercise + nutrition group against the health education group. No significant difference in SMI, but Ex + N group 3 times more likely to improve muscle strength than HE group.	Yes, aerobic and resistance training both included for Ex + N and Ex alone groups.