Table 2.

Clinical features of minerals deficiency (hypocalcemia, hypomagnesemia, hypophosphatemia, hyponatremia, and hypokalemia).

Element	Clinical Manifestations Associated with Deficiency
Magnesium (Mg)	Electrolyte disturbance: hypokalemia (renal potassium wasting, decreased intracellular potassium), hypocalcemia [62]
	Neuromuscular and central nervous system: positive Chvostek and Trousseau signs, spontaneous carpal-pedal spasm, seizures, vertigo, ataxia, nystagmus, athetoid, and choreiform movements, muscular: weakness, tremor, fasciculation, and wasting [64,65]
	Psychiatric: depression, psychosis [65,66]
	Cardiovascular: cardiac arrhythmia, (electrocardiographic: prolonged PR and QT intervals, U waves, atrial tachycardia, premature contractions, fibrillation, hypertension, junctional arrhythmias, ventricular premature contractions, tachycardia, fibrillation, sensitivity to digitalis intoxication), myocardial ischemia/infarction, hypertension, atherosclerotic vascular disease, preeclampsia, atrial tachycardias, fibrillation, supraventricular arrhythmias, ventricular arrhythmias, torsade de pointes, digoxin sensitivity [67]
	Miscellaneous: migraine, asthma, chronic fatigue syndrome, athletic performance [68]
	Bone and mineral metabolism: hypocalcemia (impaired parathyroid hormone secretion, renal and skeletal resistance to parathyroid hormone, resistance to vitamin D), osteoporosis [67]
	Complications of magnesium deficiency: altered glucose homeostasis, atherosclerotic vascular disease, hypertension, myocardial infarction [65]
Calcium (Ca)	Cardiovascular: the characteristic electrocardiographic finding in hypocalcemia is a prolonged QTc. Cardiomyopathy or congestive heart failure may rarely result from prolonged hypocalcemia, cardiac arrhythmias [69]
	Increased neuromuscular excitability: tetany (when caused by respiratory alkalosis: hyperventilation-induced tetany), paresthesia, muscle spasms, and cramps, Chvostek’s sign, Trousseau’s sign, seizures [70,71]
	Central nervous system: ranging from generalized fatigue and depression to confusion, delirium or coma, calcification of the basal ganglia and other intracerebral calcifications [68]
Sodium (Na)	Mild symptoms: anorexia, nausea, vomiting, headache, muscle cramps [72]
	Moderate symptoms: muscle weakness, lethargy, confusion [73]
	Severe symptoms: seizures, altered consciousness, coma [73]
Potassium (K)	Muscular: muscle weakness, paralysis, muscle cramps and spasms, deep tendon reflexes [74,75]
	Cardiovascular: cardiac arrhythmias (e.g., premature atrial and ventricular complexes, ventricular fibrillation [76]
	Other symptoms: nausea, vomiting, constipation, fatigue, polyuria [74,77]
Phosphorous (P)	Cardiovascular system: hypophosphatemic cardiomyopathy, and arrhythmias [78,79]
	Muscle composition: total phosphorous and magnesium are abnormally low, whereas sodium, chloride, and calcium are abnormally elevated. Potassium content of skeletal muscle is low. The muscle weakness and osteomalacia can occur in severe chronic depletion of profound hypophosphatemia may be accompanied by rhabdomyolysis, especially in acute alcoholism [80]
	Respiratory insufficiency: hypoxia, respiratory acidosis, peripheral neuropathy, weakness, or muscle paralysis [81,82]
	Erythrocyte/leukocyte dysfunction/platelet disorders: hematologic disturbances of profound hypophosphatemia include hemolytic anemia, decreased release of oxygen from hemoglobin, as well as impaired leukocyte and platelet function. 50% reduction in chemotactic, phagocytic, bactericidal activity of granulocytes, 2,3-DPG in erythrocytes [81]
	Nervous system: neuromuscular disturbances, progressive encephalopathy, seizures, coma, and death, brain stem dysfunction, peripheral neuropathy, encephalitis [65]
	Metabolic acidosis: mobilization of bone mineral and hypercalciuria, an increase in intracellular pH [82]
Selenium (Se)	Cardiovascular: Keshan disease is congestive cardiomyopathy associated with heart failure, cardiac enlargement, electrocardiogram (ECG) abnormalities, gallop rhythm, and even cardiogenic shock [83]
	Endocrine System: of the 35 selenoproteins that have been identified so far, 3 of them are called Iodothyronine deiodinases, and they play a role in thyroid hormone metabolism. The thyroid contains the maximum concentration of selenium of all the organs in our bodies. One of the iodothyronine deiodinases converts inactive thyroxine to its active form. The second one is abundant in the central nervous system (CNS), brown fat and skeletal muscles and also plays a role in the activation of thyroid hormones. The third has a role in deactivating thyroid hormones [84]
	Immune System: glutathione peroxidase (G-Px) is a selenium-dependent enzyme that protects cell membranes and lipid-containing organelles from peroxidative damage by inhibition and destruction. It acts in combination with vitamin E to maintain the integrity of the cell membranes, participating in redox reactions with hydrogen peroxide-producing glutathione. Selenium deficiency exacerbates the redox by-product toxicity and oxidative damage to cell membranes [85]
	Musculoskeletal: Kashin–Beck disease is a disabling deformity of bones, cartilage, and joints leading to enlarged joints and restricted movements. Both Keshan disease and muscular syndrome have been described in patients on total parenteral nutrition (TPN) who did not have selenium added to their supplement. Symptoms described included intermittent myalgias and tenderness as well as eventual white fingernail beds [86]
	Neurological and psychiatric: studies have shown that selenium deprivation can lead to depressed mood and more hostile behavior. The turnover rate of some neurotransmitters has also been found to be affected by selenium deficiency. Selenium concentration in the brain of patients with Alzheimer’s disease was found in one study to be about 60% of that of controls [87,88]
	Reproductive System: selenium is essential for testosterone biosynthesis and the formation and development of normal spermatozoa. Testicular tissue contains large concentrations of selenium and is responsible for sperm quality and male fertility health [86]
Zinc (Zn)	Brain: neuropsychiatric disorders, neurosensory disorders, decreased nerve conduction, mental lethargy [89,90]
	Thymus: thymic atrophy [91]
	Skin: skin lesions, acrodermatitis, decreased wound healing [92]
	Reproductive system: hypogonadism [91]
Chromium (Cr)	Chromium insufficiency has been hypothesized to be a contributing factor to the development of type 2 diabetes and atherosclerosis [93]
	Psychiatric: an abrupt rise in anxiety levels, a sudden decrease in energy level, chronic fatigue, signs of muscle weakness, slow growth rate, mood swings [93]