Table 1.

Supplements demonstrating efficacy through specific doses able to maintain musculoskeletal health.

Supplements	Model	Sample Size	Administration (Dose/Day and Duration) of Supplementation	General Effects and Possible Mechanism of Action	Effects on Microbiome Composition	Refs.
Probiotic
Lactobacillus casei Shirota	SAMP8 mice	24	1 × 108 or 1 × 109 CFU/mouse/day × 12 weeks	↓ signaling mediators (inflammatory cytokines and SCFAs); = mitochondrial and muscle functions	↑ Odoribacter, ↑ Oscillibacter, ↑ Lachnospiraceae UCG 006	[148]
Bifidobacterium longum OLP-01	ICR mice	40	2.05 × 109; 4.10 × 109; and 1.03 × 1010 CFU/kg/day for 4 weeks	↓ lactate, ammonia, and CK levels	↑ Lactobacillus, ↑ Clostridium, ↑ Bifidobacterium, ↑ Lactococcus, ↓ Bacillus, ↓ Enterococcus, ↓ Akkermansia	[149]
Lacticaseibacillus paracasei PS23	SAMP8 mice	80	1 × 109 CFU/mouse/day for 12 weeks	↑ lean mass, restored muscle strength, ↑ SOD, ↑ gpx in muscles		[150]
Lactobacillus plantarum TWK10	ICR mice	33	1 × 109 CFU/mouse/day for 6 weeks	Prevention of muscle weakness associated with aging, ↑ concentration of glycogen in muscle tissue	↓ Enterobacteriaceae, ↓ Enterococcaceae, ↑ Lactobacillaceae	[151,152]
Lactobacillus plantarum TWK10	ICR mice	24	2.05 × 108, 1.03 × 109 units/kg/day for 6 weeks	↑ muscle mass (gastrocnemius muscle), ↑ energy harvesting, health promotion, performance improvement, anti-fatigue effects		[153]
Limosilactobacillus fermentum DR9	Sprague Dawley rats,	18	10 log CFU/rat/day for 12 weeks	↓ p53, increase in IGF-1 anabolic factors, prevention of aging-induced metabolic diseases	Inhibited growth of pathogens Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis	[154]
Lactobacillus Paracasei OFS 0291
Lactobacillus helveticus OFS 1515
Kefir	ICR mice	32	2.15, 4.31, and 10.76 g/kg/day for 4 weeks	↑ exercise performance, ↑ forelimb grip strength, ↑ swimming time to exhaustion	↓ Firmicutes/ Bacteroidetes ratio	[155]
Prebiotics
FOS and inulin	Human	50	one spoon/ day for 13 weeks	↑ levels of fatigue, ↑ muscle strength		[156,157]
GOS	Human	39	4 g/ twice daily for 3 weeks	Production of butyrate	↑ bifidobacteria, ↑ lactobacilli	[158,159]
1-kestose	Human super-elderly patients	6	10 g/day for 12 weeks	↑ index of skeletal muscle mass, ↓ body fat	↑ Bifidobacterium longum	[158,159]
SCFAs
β-hydroxy-β-methylbutyrate (HMB)	Human	43	1.5 g twice daily for 12 weeks	↑ muscle mass, ↑ muscle strength		[160]
HMB/Arg/Lys mixture	Human	77	2 g/5 g/1.5 g per day) for 1 year	↑ lean tissue mass, ↑ protein turnover		[161]
HMB	Human	79	2 g/day for 2 or 4 weeks	↓ urinary urea nitrogen excretion		[162,163,164,165,166,167,168]
HMB	Human	31		↑ body fat loss		[162,163,164,165,166,167,168]
HMB/Arg/Lys mixture	Human	57	2/5/1.5 g per day for 12 weeks	↑ limb circumference, ↑ leg and handgrip strength, ↑ body protein synthesis		[162,163,164,165,166,167,168]
HMB/Arg/Lys mixture	Human	77	2/5/1.5 g per day for 1 year	↑ muscle mass, ↑ muscle strength		[162,163,164,165,166,167,168]
HMB/Arg/Gln mixture	Human	35	4 g HMB/14 g Arg/14 g Gln for 2 weeks	↑ collagen synthesis in muscle		[162,163,164,165,166,167,168]
HMB	Human	80	(1.5 g/day) + mild fitness program for 8 weeks	↑ muscle strength, ↑ physical performance parameters		[162,163,164,165,166,167,168]
Curcumin
	BALB/c mice		0.2% (w/w) nanoparticle curcumin mixed with normal rodent diet for 7 days	Suppression of the activation of NF-kB	↑ butyrate-producing bacteria and Clostridium cluster IV	[169]
	Human	32	6 tablets daily; 6000 mg for 4/8 weeks		↑ Clostridium, ↑ Bacteroides, ↑ Citrobacter, ↑ Cronobacter, ↑ Enterobacter, ↑ Enterococcus, ↑ Klebsiella, ↑ Parabacteroides, ↑ Pseudomonas, ↓ Blautia, ↓ Ruminococcus	[170]
Curcumin + HPβCD	C57BL6J and C57BL10ScSn mice	143	every sixth day, for 6 months, with120 μg/kg	↑ satellite cell commitment and recruitment		[171]
Quercetin
Quercetin glycosides	Male C57BL/6J mice		Two dosages (1.5 or 3.0 g/L) for 24 weeks	↑ Strength and rotarod performance, ↑ wet weights		[172]
Resveratrol	Wistar rats		400 mg/kg/day	↓ muscle fiber atrophy		[173]
Ω-3 fatty acids
Linolenic acid	Caenorhabditis elegans		50 μg mL−1	repair of mitochondrial function by promoting mitophagy and fighting oxidative stress		[174]

CFU = colony-forming units; CK = creatine kinase; SOD = superoxide dismutase; IGF-1 = insulin-like growth factor-1; ↑ = increase; ↓ = decrease.