Table 1.
Mechanisms of action and outcome readouts for efficacy in preclinical and/or clinical studies, for dietary supplements most commonly used in DMD.
Compound | Claimed mechanism of action | Preclinical studies in mdx mice: assessed endpoints | Evidences from clinical trials in DMD patients |
---|---|---|---|
Branched-chain amino acids | Increase protein synthesis | Modulation of vascular function | ↓ Protein degradation [50] |
Myofibre phenotype | No improvements [51] | ||
Motor function [206] | |||
L-arginine | Enhance utrophin expression | Utrophin expression [62,63] | In combination with metformin (AMPK activator) [60]: |
Necrosis [63] | ↑ Activity of mitochondrial electron transport chain | ||
Respiratory function [63] | ↓ Oxidative stress | ||
↑ Clinical scores | |||
Glutamine | Antioxidant activity | Oxidative stress | ↑ Insulin secretion [83] |
Protein breakdown [207] | ↓ Protein degradation [82] | ||
No effect on muscle function or strength [80,81] | |||
Creatine | Enhance metabolism | Necrosis [86,87] | ↑ (PCr)/inorganic phosphate (Pi) ratio [90] |
↑ Ca2+-ATPase (SERCA2) content | Energy metabolism [86,88] | ↑ Muscle strength [90,919293] | |
Muscle force [87,88,89] | ↓ Markers of bone breakdown [92] | ||
↑ Fat free mass [92] | |||
Taurine | Antioxidant and anti-inflammatory activity; restoration of Ca2+ homeostasis | Muscle damage [103] | |
Oxidative stress [103] | |||
Muscle function [89] | |||
Membrane conductivity [89] | |||
Cardiac function [104] | |||
Muscle strength (in combination with prednisolone) [105] | |||
Green tea extract | Antioxidant and anti-inflammatory activity | Muscle damage and CK plasma levels [110,111] | Clinical trial ended but data not available |
Necrosis [111,112113] | |||
Regeneration [110] | |||
Oxidative stress [111,112113] [208], | |||
Muscle force [111,113] | |||
Protandim | Antioxidant and anti-inflammatory activity | Oxidative stress markers [114] | |
Omega-3 fatty acids | Anti-inflammatory activity | Necrosis [133] | ↓ Insulin resistance |
Inflammation [133,134] | Trend towards a decrease of muscle loss [135] | ||
Vitamin D | Restored insufficient 25-hydroxyvitamin D serum levels in DMD boys | Muscle force | In combination with calcium-rich diet [210]: |
Muscle damage [209] | ↑ Bone mineral density | ||
↑ Bone mineral content | |||
Resveratrol | Anti-inflammatory activity | Muscle damage (CK/LDH plasma levels) [103] | |
Oxidative stress [103,150,151] | |||
Inflammation [211] | |||
Autophagy/mitophagy [150,212] | |||
Muscle force [103] | |||
Utrophin expression [211] | |||
Curcumin | Anti-inflammatory activity | Muscle strength [152,153] | |
Muscle damage [152,153] | |||
Inflammation markers [152,153] | |||
NF-kappaB activity [152,153] | |||
N-Acetyl cysteine | Antioxidant activity | Muscle damage (CK plasma levels) [168,169] | |
Necrosis [168,169] | |||
Inflammation [169,170] | |||
Oxidative stress [169,170] | |||
βdystroglycan and utrophin expression [172] | |||
Coenzyme Q10 | Antioxidant activity | ↑ Muscle strength [179] | |
No effect on echocardiographic parameters [182] | |||
Melatonin | Antioxidant activity | Muscle damage (CK plasma levels) | ↓ Oxidative stress [187] |
Oxidative stress | ↓ Plasma pro-inflammatory cytokines [187] | ||
Muscle force [186] | ↓ Hyperoxidative status in erythrocytes [213] |