neurotransmitters , 26 nitric oxide metabolism , 26 regulation of intracellular calcium levels , 113 and transmembrane electrolyte flux . 112 In the musculoskeletal system , magnesium is involved in the relaxation of smooth muscle , 115 normal muscle function , 26 , 111 muscle contraction , 110-112 , 114 muscle relaxation , 112 bone strength , 26 bone metabolism , 110 bone mineralisation , 112 bone mineral density , 110 and bone integrity . 111 Magnesium is involved in the maintenance of normal muscle and nerve function , heart rhythm , and the immune system . 26
Manganese Manganese is essential for numerous vital process , including nerve and brain development , 116 brain physiology , 117 and cognitive functioning . 116 Manganese has antioxidant activity 22 , 116 , 117 and is a component of manganese superoxide dismutase ( MnSOD ). 116-118 It participates in enzymatic mechanisms that protect against free radicals and toxic derivatives of oxygen . 49 Manganese is involved in development , reproduction , immune function , bone growth , regulation of blood glucose , blood coagulation and haemostasis , energy metabolism , 117 and in the metabolism of proteins , lipids , and carbohydrates . 116
Molybdenum Molybdenum has versatile redox chemistry that is used by enzymes to catalyse diverse redox reactions . 119 Molybdenum forms the catalytic centre of numerous enzymes , such as nitrogenase , 120 120 , 121
nitrate reductases , sulphite oxidase , 120 , 121 xanthine oxidoreductases , 120 121 , 122
aldehyde oxidase , and mitochondrial amidoxime reductase . 122 It is involved in detoxifying excess sulphites . 121
Selenium Selenium is an antioxidant 15 , 123 , 124 and is a
15 , 123 , 125
cofactor for glutathione peroxidase and thioredoxin reductases . 123 , 125 Selenium is involved in redox reactions that can impact cellular processes , such as DNA repair . 123 , 124 It is essential for the endocrine system , the central nervous system , the cardiovascular system , reproductive biology , and muscle function . 123
Selenium is functionally essential for the immune system . 123 , 124 It plays a role in the metabolism of cartilage and bones , 124 chondrogenic differentiation , 124 functioning of the thyroid gland 15 , 123 and thyroid hormones . 124
Silica Silicon plays a vital role in bone formation , 25 , 126 bone matrix quality , facilitates bone mineralisation , 126 bone health , 25 connective tissue , 25 , 103 and skin structure . 103 It promotes the formation of collagen , 103 promotes the synthesis of elastin 103 and glycosaminoglycans , 103 , 126 and maintains blood vessel elasticity . 103
Zinc Zinc is a component of approximately 300 metalloenzymes that catalyse more than 50 different physiological reactions . 127 Zinc is an antioxidant and anti-inflammatory nutrient . 15 It is essential for growth and development 109 , 128 the metabolism of RNA and DNA , 15 signal transduction , 15 synaptic plasticity , 15 and gene expression . 15 It supports a Th1 cytokine-mediated immune response . 16 Low intracellular zinc has been found to be associated with oxidative stress . 129
N-Acetylcysteine N-acetylcysteine ( NAC ) is an amino acid that has the potential to manage chronic fatigue syndrome . N-acetylcysteine has numerous properties , including antioxidant , 27 , 130 , 131 decreases oxidative stress , 27 anti-inflammatory , 130 detoxifying , 27 and mucolytic actions , 27 and improves lipid profile . 27 , 132 N-acetylcysteine is one of the precursors of glutathione ,
27 , 131 which is an important antioxidant .
Carnitine Carnitine is an amino acid that plays an essential role in cellular energy metabolism 133 in the metabolism of fatty acids , 1 and is necessary to deliver longchain fatty acids from the cytosol into the mitochondrial matrix . 134 Carnitine has antioxidant and anti-inflammatory actions , neuroprotective function , cardioprotective effects , and improved cardiac energy metabolism . 134 A study of carnitine ( 2 g twice daily for 30 days ) found a reduction in physical and mental fatigue , along with a reduction in fat mass , total cholesterol , and an increase in muscle mass . 133 An 8-week study of acetylcarnitine ( 2 g daily for 8 weeks ) significantly improved mental fatigue and attention concentration . 135 Carnitine supplementation showed an amelioration of muscle soreness and improved muscle damage biomarkers . 134
Glutamine Glutamine is the most abundant 136-138 and versatile amino acid in the body . 137 Glutamine is essential for lymphocyte proliferation , 137 , 139 cytokine production , 137 macrophage phagocytic plus secretory activities , and neutrophil bacterial killing . 137 Glutamine is important for intermediary metabolism , 137 energy metabolism , 140 glycogenesis , 140 interorgan nitrogen exchange via ammonia transport between tissues , 137 protein synthesis , 141 enhances intestinal and whole-body growth , 43 cell proliferation , 140 cell integrity , 138 138 , 141
signal transduction , activating intracellular signalling pathways , 138 , 141 and pH homeostasis . 137
27 , 131
Along with N-acetylcysteine , glutamine is an essential precursor for the antioxidant glutathione . 141 In the digestive system , glutamine enhances intestinal and whole-body growth , 43 promotes enterocyte proliferation , 43 , 136 regulates tight junction proteins , 136 regulates intestinal barrier function in injury and infection , 43 enhances ion transport by the gut , 43 suppresses pro-inflammatory signalling pathways , 136 and protects cells against apoptosis and cellular stresses during normal and pathologic conditions . 136 Glutamine stores are depleted during severe metabolic stress including trauma , sepsis , and inflammatory bowel diseases . 136
Probiotics Hippocrates suggested that ‘ all disease begins in the gut ’. 142 There is a marked comorbidity between disorders of the gastrointestinal system and stressrelated conditions , such as anxiety and depression . 142 Probiotics are involved in immune system development , 30 immunomodulation , 30 , 143 , 144 digestive health , 28-30 30 , 144
and intestinal wall integrity . The uses of probiotics include fatigue , 145
130 | vol29 | no3 | JATMS