Scoping review of micronutrient imbalances, clinical manifestations, and interventions

Table 1 Laboratory testing for diagnostic evaluation of several micronutrient deficiencies

Vitamin	Diagnostic test	Specimen type	Diagnostic values
A	Vitamin A (retinol) level	Serum	Low
D	Total 25-hydroxyvitamin D level	Serum	Low
E	Vitamin E (α-tocopherol) level	Serum	Low
K1	PT/INR	Serum	Prolonged/elevated
Thiamine2	Thiamine, whole blood	Whole blood EDTA	Low
Riboflavin	Riboflavin level or urinary excretion rate	Plasma or urine	Low
Niacin	Niacin level or urinary excretion of N1-methylnicotinamide	Serum or urine	Low
Pantothenic acid	Pantothenic acid level	Serum	Low
Pyridoxine3	Pyridoxal phosphate	Serum	Low
Biotin	Biotin level	Serum	Low
Folate	Vitamin B12 and folate levels	Serum	Low
Cobalamin4	Vitamin B12 and folate levels	Serum	Low
Ascorbic acid5	Ascorbic acid level	Serum	Low

¹If phytonadione (Vitamin K1) 1 mg IV dramatically decreases PT within 2-6 hours, a liver disorder is unlikely, and the diagnosis of vitamin K deficiency is confirmed.

²This assay measures the concentration of the primary active form of vitamin B1 (thiamine diphosphate). Approximately 90 percent of B₁ present in whole blood is thiamine diphosphate. Thiamine monophosphate and thiamine, which comprise the remaining 10 percent, are not measured. Values less than 70-180 nmol/L are considered diagnostic for thiamine deficiency. The United States Food and Drug Administration has not cleared or approved it. The thiamine loading test, which measures erythrocyte transketolase in red blood cells, is still the best indicator for thiamine deficiency. However, the test is expensive and time-consuming.

³Diagnosis of pyridoxine deficiency is usually made clinically. There is no single acceptable laboratory testing to confirm diagnosis. However, serum pyridoxal phosphate is usually the most common.

⁴A complete blood count, in conjunction with B12 and folate levels, should be obtained to detect megaloblastic anemia. Folate levels should also be measured to differentiate B12 from folate deficiency as a cause of anemia, as folate supplementation may alleviate megaloblastic anemia but worsen neurologic deficits.

⁵Vitamin C deficiency is a clinical diagnosis based on risk factors and gingival or skin findings. Laboratory diagnosis requires the measurement of blood ascorbic values. < 0.2 mg/dL (< 11 mcmol/L) indicate vitamin C deficiency.

PT: Prothrombin time; INR: International normalized ratio; EDTA: Ethylenediaminetetraacetic acid.

Table 2 Summary of medical therapy for several micronutrient deficiencies in adult patients

Vitamin	Clinical manifestations of deficiency	Recommended treatment
A	Nyctalopia, xerosis cutis, xeropthalmia, immunosuppression, keratomalacia, and conjunctival squamous metaplasia Bitot spots	Vitamin A palmitate 60000 IU (18000 mcg RAE) orally once per day for 2 days, followed by 4500 IU once a day
D	Bone pain, muscle weakness, depression, hair loss, and hypocalcemic tetany	Ergocalciferol (vitamin D2) 50000 IU orally every 7 days for 8 weeks
E	Hemolytic anemia, muscle weakness, ataxia, and decreased proprioception and vibration	α-tocopherol is 15 to 25 mg/kg orally once daily or 200 IU of mixed tocopherols daily. Injections should be used to treat neuropathy and patients with malabsorption syndromes
K	Increased risk for bleeding	Phytonadione 1 to 10 mg orally for nonemergent correction of prolonged INR in patients taking anticoagulants. When partial correction of INR is desirable (i.e., prosthetic heart valve), 1 to 2.5 mg doses should be used
Thiamine	Wernicke encephalopathy: Confusion, ophthalmoplegia, nystagmus, and ataxia. Korsakoff syndrome: Confabulations, personality changes, and permanent memory loss. Wernicke-Korsakoff syndrome: Presentation is a combination of Wernicke and Korsakoff syndrome. Dry beriberi: Polyneuropathy and symmetric muscle wasting. Wet beriberi: High-output heart failure	IV thiamine 250-500 mg/day should be given for 3-5 days, followed by oral thiamine 250-300 mg/day for chronic alcoholics and other patients at risk for deficiency. Patients with suspected Wernicke receive 500 mg of thiamine diluted in 50-100 mL of normal saline infused over 30 minutes three times daily for three days, followed by 250 mg IV daily for 3 to 5 days or until clinical improvement. 100 mg IV once per day for several days in patients with edema and congestion due to cardiovascular beriberi
Riboflavin	Cheilosis and corneal vascularization	5 to 30 mg orally once per day until recovery. Other water-soluble vitamins should also be given
Niacin	Diarrhea, dermatitis, and dementia (also hallucinations)	Nicotinamide 250 to 500 mg orally once per day
Pantothenic acid	Enteritis, dermatitis, alopecia, and adrenal insufficiency may lead to “burning feet syndrome”	Pantothenic acid 5-10 mg orally once per day
Pyridoxine	Hyperirritability, peripheral neuropathy, convulsions, and sideroblastic anemia	Pyridoxine 50-100 mg orally once per day. Patients taking isoniazid should be given 30-50 mg orally once a day
Biotin	Isolated deficiency is relatively rare. Enteritis, dermatitis, and alopecia	Biotin 5-20 mg orally once per day
Folate	Megaloblastic anemia, glossitis, fatigue, and pale skin	Folic acid 400-1000 mcg orally once per day. Women who plan on becoming pregnant should be supplemented with 400 to 800 mcg once per day
Cobalamin	Megaloblastic anemia, paresthesias, depression/anxiety, pale skin, cognitive dysfunction, and SCD	Vitamin B12 1000-2000 mcg orally once per day in patients who are significantly deficient or possess neurologic symptoms. For severe deficiency, 1 mg IM 1-4 times per week for several weeks until anemia and symptoms resolve
Ascorbic acid	Scurvy-swollen gums, petechiae, anemia, poor wound healing, hemarthrosis, “corkscrew” hair, and perifollicular and subperiosteal hemorrhages	For scurvy, use 500-1000 mg orally once per day for 1-2 weeks until symptoms and signs resolve

IU: International units; RAE: Retinol activity equivalents; INR: International normalized ratio; IV: Intravenous; SCD: Subacute combined degeneration; IM: Intramuscular.