Vitamins are organic compounds that cannot be synthesized by humans but are required as nutrients in minute amounts for normal metabolism. Vitamins have several different functions: They may regulate cell growth and differentiation, as catalysts, as antioxidants, and as coenzymes. Vitamins are classified as either fat soluble (vitamins A, D, E, K) or water soluble (B group of vitamins and C). Deficiency of most vitamins is rare in Western countries. Certain groups may be prone to vitamin deficiency, and these are discussed here. Vitamin D deficiency is discussed in a separate topic.

Hypovitaminosis

Vitamin A: Retinol

Vitamin E: Alpha tocopherol

Vitamin K: Phytonadione or menadiol

Vitamin B₁: Thiamine

Vitamin B₂: Riboflavin

Niacin: Vitamin B₃; nicotinic acid

Vitamin B₅: Pantothenic acid

Vitamin B₆: Pyridoxine; pyridoxal phosphate

Folic acid: Vitamin B₉; folate

Vitamin B₁₂: Cyanocobalamin

Vitamin C: Ascorbic acid

Deficiency can occur in all age groups but is most common in the elderly.

• Vitamin A deficiency: Affects 250 million preschool children worldwide.
• Vitamin E deficiency: Deficiency is rare in humans. Usually occurs in individuals with severe protein-energy malnutrition.
• Vitamin K deficiency: Varies by geographic regions; no race predilection; affects both sexes equally. Encountered often in infants. In normal healthy adults, 8% to 31% have vitamin K deficiency, but it rarely leads to significant bleeding.
• Vitamin B₁ (thiamine) deficiency: Incidence is unknown; no sex, race, or age predilection. Deficiency is usually due to inadequate intake, especially if consuming diet made up of polished rice and grains.
• Vitamin B₂ (riboflavin): More common than previously appreciated. Deficiency is referred to as ariboflavinosis.
• Vitamin B₅ (pantothenic acid) deficiency: Rare, as it is present in all foods.
• Vitamin B₁₂ (cobalamin) deficiency: Relatively common. Of patients with anemia, about 1% to 2% is due to B₁₂ deficiency. Among patients with macrocytosis (mean corpuscular volume [MCV] >100) 18% to 20% is due to B₁₂ deficiency. Occurs in all age groups but more common in the elderly. B₁₂ deficiency due to pernicious anemia is common in Northern Europe.
• Vitamin B₉ (folic acid) deficiency: Mandatory fortification started in 1998. Prevalence before fortification 16% and after 0.5%. Neural tube defect associated with low maternal folate status during pregnancy. Pregnant women and the elderly are at greatest risk of folic acid deficiency.
• Vitamin C (ascorbic acid) deficiency: Smokers and low-income persons are at increased risk. Vitamin C deficiency is associated with access to food and/or socioeconomic status. Prevalence vary worldwide, but the rate is about 7.1% in the U.S.

Fig. 1 shows environmental and nutritional factors in disease.

• Vitamin A: Xerophthalmia, xerosis of the cornea, keratomalacia, Bitot spots (abnormal squamous cell proliferation and keratinization of the conjunctiva), nyctalopia (poor adaptation to darkness)/night blindness, poor bone growth, dry skin and hair, follicular hyperkeratosis (caused by blockage of hair follicles by keratin), pruritus, broken fingernails
• Vitamin K: Clinical manifestation usually occurs if hypoprothrombinemia is present. Major symptom is bleeding to minor trauma. Also can show easy bruisability, epistaxis, hematoma, gum bleeding, melena, hematuria, or splinter hemorrhage
• Vitamin E: Neuromuscular disorders (ataxia; hyporeflexia, peripheral neuropathy); bone weakness, hemolysis
• Vitamin B₁ (thiamine): Beriberi, which has two subtypes (infantile and adult). Adult type is described below:
  1. Dry beriberi (affecting the nervous system): Symmetrical peripheral neuropathy (with sensory and motor impairments), Wernicke encephalopathy (nystagmus, ataxia, ophthalmoplegia, and confusion), Korsakoff syndrome (impaired short-term memory loss and confabulation but normal cognition)
  2. Wet beriberi (affecting the cardiovascular system): Cardiomegaly, cardiomyopathy, heart failure, tachycardia, hypotension, chest pain, peripheral edema
  3. Gastrointestinal (GI): Anorexia; constipation
• Vitamin B₂ (riboflavin):
  1. Cheilosis (chapping and fissure of the lip)
  2. Glossitis (sore red tongue)
  3. Oily, scaly rashes on nasolabial folds, eyelids, scrotum, labia majora
  4. Red itchy eyes
  5. Normocytic or normochromic anemia
  6. Peripheral neuropathy
• Vitamin B₃ (niacin):
  1. Pellagra (4 Ds-diarrhea, dermatitis, dementia, and ultimately death)
  2. Hyperpigmentation of sun-exposed skin
  3. “Raw beef” swollen and painful tongue
  4. Deficiency can be seen in prolonged use of Isoniazid, in carcinoid syndrome, and in Hartnup syndrome
• Vitamin B₅ (pantothenic acid):
  1. Deficiency is rare
  2. Deficiency leads to “burning feet syndrome” (distal paresthesia and dysesthesia)
  3. Anemia
  4. GI symptoms
• Vitamin B₆ (Pyridoxine): Rare to see overt deficiency
  1. Mild deficiency-glossitis, cheilosis, impaired proprioception; sensory ataxia, confusion, depression
  2. Severe deficiency-seborrheic dermatitis, seizure, microcytic
• Vitamin B₁₂ (cyanocobalamin):
  1. Megaloblastic anemia (pernicious anemia)
  2. Neurologic symptoms including peripheral neuropathy, ataxia (shuffling gait), paresthesia; subacute degeneration of the spinal cord (demyelination of the dorsal column), visual disturbances due to optic atrophy
  3. Glossitis and GI symptoms such as nausea, vomiting, and anorexia are also common
  4. Patients may also have dementia/mental sluggishness, depression, and weakness
• Vitamin B₉ (folic acid):
  1. Patchy hyperpigmentation of skin (especially between fingers and toes) and mucous membranes
  2. Moderate fever (temp <102° F; 38.9° C) despite the absence of infection
  3. Neural tube defect
  4. Angular stomatitis
  5. Red, beefy, smooth, and shiny tongue
  6. Megaloblastic anemia
• Vitamin C: Scurvy (bruising, petechiae, follicular hyperkeratosis, perifollicular hemorrhage, corkscrew hairs), poor wound healing, fatigue, gingivitis/bleeding gums, weight loss, bone abnormalities (Fig. E2). Also, loss of teeth, abnormal nail (koilonychia and splint hemorrhages). Vitamin C deficiency may be associated with nonalcoholic fatty liver

• Fat-soluble vitamins (vitamins A, D, E, K):
  1. Decreased ingestion, malnutrition, eating disorders
  2. Diseases that affect fat absorption decrease the absorption of fat-soluble vitamins-for example, cystic fibrosis, celiac sprue, inflammatory bowel disease, cholestasis, hepatobiliary disease, small bowel surgery
  3. Change in vitamin metabolism:
     1. Alcoholism
     2. Drugs such as cholestyramine, warfarin, anticonvulsants, antibiotics (e.g., cephalosporins)
     3. Chronic kidney disease
• Increased risk in:
  1. Vegans
  2. Recent immigrants
  3. Refugees
  4. Toddlers/preschoolers living below the poverty line
• Water-soluble vitamins (the B group of vitamins and vitamin C)-there are several etiologic factors, including:
  1. Inadequate intake
  2. Decreased absorption
  3. Alcoholism
  4. Pregnancy/lactation
  5. Peritoneal dialysis
  6. Medications (e.g., isoniazid, phenothiazines, tricyclic antidepressants, metformin [vit B₁₂])
  7. Malabsorption
  8. Low income
  9. Advanced age
• Vitamin B₁₂ deficiency-caused by:
  1. Insufficient dietary intake, as in strict vegans
  2. Decreased absorption secondary to intrinsic factor deficiency, decreased intrinsic factor secretion, gastric atrophy, gastrectomy/gastric bypass
  3. Terminal ileum disease such as celiac disease, enteritis, tropical sprue
• Folic acid deficiency:
  1. Increased needs can lead to deficiency (e.g., pregnancy, lactation, malignancy)
  2. Derangement of folate metabolism by:
     1. Medication (e.g., methotrexate)
     2. Disease (e.g., hypothyroidism)
     3. Increased excretion: As seen in alcoholics

Table 1 summarizes clinical clues in identifying vitamin deficiency.

General initial laboratory tests include:

• CBC
• Liver function tests
• Basic metabolic panel
• Albumin
• Measurement of serum levels of the specific vitamin in question

Specific tests may be considered in the following cases:

• Vitamin A:
  1. Serum retinol level (best test, a direct measure, expensive)
  2. Retinol binding protein (easier to perform, less expensive)
  3. Dark-adaptation threshold test
• Vitamin K:
  1. Protein induced by vitamin K absence or antagonism is the current best test available to determine vitamin K status. The level is increased in vitamin K deficiency
  2. Prothrombin time/partial thromboplastin time
  3. Prothrombin
  4. Des-gamma-carboxyprothrombin (most sensitive test)
  5. Niacin: Urine-N-methylnicotinamide (level <0.8 mg/day indicates niacin deficiency)
• Vitamin B₁ (thiamine):
  1. Blood thiamine levels
  2. Thiamine pyrophosphate levels in blood
  3. Erythrocyte thiamine transketolase activity
  4. Urinary thiamine excretion
• Vitamin B₃ (niacin): Check urinary N-methylnicotinamide or erythrocyte NAD/NADP ratio (tests are not readily available)
• Vitamin B₂: Check plasma riboflavin concentration
• Vitamin B₁₂:
  1. Serum vitamin B₁₂ <190 pg/ml is diagnostic of vitamin B₁₂ deficiency
  2. Serum methylmalonic acid, which is elevated in B₁₂ deficiency
  3. Antiparietal antibody
  4. Intrinsic factor antibody is decreased
  5. CBC shows increased MCV, anemia with low hemoglobin, and low hematocrit
  6. Blood smear shows macrocytosis and hypersegmentation of megaloblasts
  7. Megaloblastic anemia
• Folic acid:
  1. Check serum folate level.
  2. Additional testing includes checking for serum homocysteine level, which will be elevated.
  3. Red cell folate level shows chronic folate status.

Anemia, Pernicious (Related Key Topic)

Osteomalacia and Rickets (Related Key Topic)

Vitamin D Deficiency (Related Key Topic)

Wernicke Syndrome (Related Key Topic)

Vitamins and Their Functions (Appendix IIb) (Related Key Topic)