Vitamins

Vitamins are a group of nutrients needed for normal cell function, growth and development, and thus, are essential for life. There are 13 essential vitamins divided into 2 categories, depending on whether they are fat or water soluble. Fat-soluble vitamins (FSVs) are readily stored in fat following absorption. Water-soluble vitamins (WSVs), though readily absorbed, are washed out and do not have a significant storage pool. The fat-soluble vitamins are A, D, E, and K. Water-soluble vitamins (see Table 20.1) include vitamin C (ascorbate) and the vitamin B complex: thiamine (vitamin B₁), riboflavin (vitamin B₂), niacin (vitamin B₃, nicotinic acid), pantothenic acid (vitamin B₅), pyridoxine (vitamin B₆), biotin (vitamin B₇), folate (vitamin B₉), and cobalamin (vitamin B₁₂).

Table 20.1. Vitamin Deficiency States, Recommended Intake, Deficiency Symptoms, Deficiency Risk Factors, Diagnostic Tests, and Therapeutic Dosages

Nutrient	Recommended Intake	Deficiency Name	Deficiency Symptoms	Deficiency Risk Factors	Diagnostic Tests	Food Sources	Recommended Therapeutic Dosage
Vitamin A			Night blindness, infection (measles), keratomalacia	Fat malabsorption	Serum retinol, serum retinol-binding protein	Liver, eggs, dairy, vegetables	50,000-200,000 IU, orally, dependent on age (see text)
AI infants	0-6 mo 1320 IU/d
AI infants	7-12 mo 1650 IU/d
RDA 1-18 y	1-3 y 1000 IU/d
	4-8 y 1430 IU/d
	9-13 y 2000 IU/d
	14-18 y 2310-3000 IU/d
Vitamin D		Rickets	Rickets, hypocalcemia, tetany, osteomalacia, hypophosphatemia	Fat malabsorption, lack of sunshine	X-ray, serum 25-OH-D with deficiency symptoms	Fatty fish, egg yolk, fortified dairy products	2000-5000 IU day for children with normal GI function (see text)
AI infants	infants 400 IU/d
RDA 1-18 y	>1 y 600 IU/d
	Preterm infants:
	<1000 g
	200-400 IU/d
	>1500 g 400 IU/d
Vitamin E			Neuropathy, ataxia	Fat malabsorption	Serum alpha-tocopherol	Grain and vegetable oils	25 IU/kg/day for fat malabsorption, up to 200 IU/day (age 1 mo-3 y) and 800 IU/day (age 14-18 y)
AI infants	0-6 mo 4 mg/d
AI infants	7-12 mo 5 mg/d
RDA 1-18 y	1-3 y 6 mg/d
	4-8 y 7 mg/d
	9-13 y 11 mg/d
	14-18 y 15 mg/d
Vitamin K		Newborn deficiency bleeding	Bleeding	Fat malabsorption, breastfeeding	PT, PIVKA, clotting factors	Green vegetables, soy oil, seeds, fruits, cow milk	1 mg, intramuscularly, in newborn infants; older children, 5-10 mg intramuscularly ×1
AI all ages	0-6 mo 2 mcg/d
	7-12 mo 2.5 mcg/d
	1-3 y 30 mcg/d
	4-8 y 55 mcg/d
	9-18 y 60-75 mcg/d
Thiamine (B₁)		Beriberi or Wernicke encephalopathy	Beriberi: symmetrical, peripheral neuropathy, edema; Wernicke; ophthalmoplegia, nystagmus, ataxia	HIV, alcohol abuse, dialysis, gastrointestinal tract disease, total parenteral nutrition, anorexia, furosemide, food faddism; inflammation in pediatric intensive care unit	Whole blood/RBC transketolase activation test, baseline and after TPP; or TPP level, urinary total thiamine	Unrefined grain, liver, pork, vegetables, dairy, peanuts, legumes, fruits, eggs	Severe: 50-100 mg parenteral ×1, followed by 10-25 mg/day parenteral × 2 wk, followed by 5-10 mg/day, orally, ×1 mo. Mild: 10 mg/day, orally, until resolution
AI infants	0-6 mo 0.2 mg/d
AI infants	7-12 mo 0.3 mg/d
RDA 1-18 y	1-3 y 0.5 mg/d
	4-8 y 0.6 mg/d
	9-13 y 0.9 mg/d
	14-18 y 1-1.2 mg/d
Riboflavin (B₂)			Pharyngitis, cheilosis, angular stomatitis, glossitis, seborrheic dermatitis	Weaning from breastfeeding, breastfed from deficient mother, alcoholism, phototherapy, cystic fibrosis, malnutrition, thyroid insufficiency, adrenal insufficiency	RBC or 24-h urine riboflavin level or RBC glutathione reductase (but of limited value in glutathione reductase deficiency, G6PD deficiency, or beta-thalassemia)	Milk, cheese, eggs, liver, lean meats, green vegetables	Infants: 0.5 mg, orally, twice/wk. Children: 1-3 mg, orally, dose 3 ×/day until resolution
AI infants	0-6 mo 0.3 mg/d
AI infants	7-12 mo 0.4 mg/d
RDA 1-18y	1-3 y 0.5 mg/d
	4-8 y 0.6 mg/d
	9-13 y 0.9 mg/d
	14-18 y 1-1.3 mg/d
Niacin (B₃)		Pellagra	Diarrhea, dermatitis, dementia, glossitis, angular stomatitis, sun exposed	Crohn disease; anorexia nervosa; Hartnup disease; Carcinoid syndrome; immigrant from area with nonfortified grains; medications isoniazid, anticonvulsants, antidepressants, 5-fluorouracil, 6-mercap-topurine, chloramphenicol, sulfas	24-h niacin and N-methylni-cotinamide; or RBC NAD/NADP niacin number	Beef, liver, fish, pork, wheat flour, eggs, beans, fortified cereals	50-100 mg/dose, orally, 3×/day
AI infants	0-6 mo 2 mg/d
AI infants	7-12 mo 4 mg/d
RDA 1-18y	1-3 y 6 mg/d
	4-8 y 8 mg/d
	9-13 y 12 mg/d
	14-18 y 14-16 mg/d
Pantothenic acid (B₅)			Not characterized		24-h pantothenic acid	Chicken, beef, potatoes, oats, tomatoes, liver, kidney, yeast, egg yolk, broccoli	No deficiency state described in children
AI all ages	0-6 mo 1.7 mg/d
	7-12 mo 1.8 mg/d
	1-3 y 2 mg/d
	4-8 y 3 mg/d
	9-13 y 4 mg/d
	14-18 y 5 mg/d
Pyridoxine (B₆)			Glossitis, cheilosis, angular stomatitis, depression, confusion	Chronic renal failure, leukemia; pyridoxine-dependent seizure; alcoholism; Medications isoniazid, hydralazine, penicillamine, theophylline	Plasma pyridoxal 5′-phosphate; 24-h urine 4-pyridoxic acid	Meat, liver, kidneys, eggs, milk, vegetables, fortified cereals	Without neuropathy: 5-25 mg orally/day × 3 wk. With neuropathy: 10-50 mg/day, orally × 3 wk; then followed by 1.5-2.5 mg/day, orally. Seizures: 50-100 mg, intravenously or intramuscularly
AI infants	0-6 mo 0.1 mg/d
AI infants	7-12 mo 0.3 mg/d
RDA 1-18 y	1-3 y 0.5 mg/d
	4-8 y 0.6 mg/d
	9-13 y 1 mg/d
	14-18 y 1.2-1.3 mg/d
Biotin (B₇)			Hypotonia, exfoliative dermatitis	Infants with TPN without biotin, eating large amounts of undercooked eggs, holocarboxylase synthase deficiency, biotinidase deficiency, biotin transport defect, anticonvulsants	Urinary biotin or urinary 3-hyroxyisovaleric acid; lymphocyte propionyl-CoA carboxylase concentration, or leukocyte LSC19A3 transporter	Chard, tomatoes, romaine lettuce, carrots, grains, liver, egg	Acquired deficiency: 150 mcg/d
AI all ages	0-6 mo 5 mcg/d
	7-12 mo 6 mcg/d
	1-3 y 8 mcg/d
	4-8 y 12 mcg/d
	9-13 y 20 mcg/d
	14-18 y 25 mcg/d
Folate (B₉)			Megaloblastic anemia, neural tube defect, cleft lip/palate	Poor intakes relatively common at 12 mo; consuming carbonated beverages; Crohn disease; fruit and carb; diarrhea; HIV, familial; medications methotrexate, trimethoprim, oral contraceptives, pyrimethamine, phenobarbital, phenytoin	Plasma or serum folate (acute); RBC folate (chronic deficiency); 5-methyltetrahydrofolate; or urinary total folate	Cauliflower, green vegetables, yeast, liver, kidney,eggs, milk, fortified grains	Infants: 0.1 mg/day orally. Children: 1 mg/day orally.
AI infants	0-6 mo 65 mcg/d
AI infants	7-12 mo 80 mcg/d
RDA 1-18 y	1-3 y 150 mcg/d
	4-8 y 200 mcg/d
	9-13 y 300 mcg/d
	14-18 y 400 mcg/d
Cobalamin (B₁₂)			Megaloblastic anemia, ataxia, muscle weakness, spasticity, incontinence, hypotension, vision problems, dementia, psychosis, mood disturbance, neural tube defect	Breastfed children of strict vegans; post bariatric surgery or stomach or ileal resection; pernicious anemia; bacterial overgrowth of gut; phenylketonuria; Whipple disease; Zollinger-Ellison syndrome; celiac disease; medications, H₂ blockers	Serum cobalamin concentration, plasma homocysteine or serum methylmalonic acid in patient with PKU	Fish, eggs, cheese, meat, poultry, milk	Children: 30-50 mcg/day, intramuscularly, ×2 wk, followed by 1 mg orally/day
AI infants	0-6 mo 0.4 mcg/d
AI infants	7-12 mo 0.5 mcg/d
RDA 1-18 y	1-3 y 0.9 mcg/d
	4-8 y 1.2 mcg/d
	9-13 y 1.8 mcg/d
	14-18 y 2.4 mcg/d
Vitamin C		Scurvy	Osmotic diarrhea, bleeding gums, arthropathy, perifollicular hemorrhage	Overcooked foods, with minimal fruits and vegetables, anorexia nervosa, autism, ulcerative colitis, Whipple disease, dialysis, alcoholics, tobacco, total parenteral nutrition without vitamin C	White blood cell ascorbate concentration, urinary ascorbate, capillary fragility, widening of zone of provisional calcification bone ends on x-rays	Citrus fruits, papaya, tomatoes potatoes	Children: 25-100 mg, orally, intramuscularly, or intravenously, 3×/day × 1 wk, followed by 100 mg orally/day
AI infants	0-6 mo 40 mg/d
AI infants	7-12 mo 50 mg/d
RDA 1-18 y	1-3 y 15 mg/d
	4-8 y 25 mg/d
	9-13 y 45 mg/d
	14-18 y 65-75 mg/d

Abbreviations: AI, adequate intake; CoA, coenzyme A; GI, gastrointestinal; HIV, human immunodeficiency virus; NAD, nicotinamide adenine dinucleotide; NADP, nicotinamide adenine dinucleotide phosphate; PKU, phenylketonuria; PIVKA, proteins-induced-in-vitamin K absence; RBC, red blood cell; RDA, recommended dietary allowance; TPN, total parenteral nutrition; TPP, thiamine pyrophosphate.

References for the table

1. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B₆, Folate, Vitamin B₁₂, Pantothenic Acid, Biotin, and Choline. National Academies Press; 1998

2. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academies Press; 2000

3. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. National Academies Press; 2011

4. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academies Press. 2001

5. Setharaman U. Vitamins. Pediatr Rev. 2006;27(2):44-55

With the exception of vitamin D, most children and adolescents who eat a diet that consists of fruits, vegetables, animal protein (meat, dairy, and eggs), cereals, and grains consume sufficient vitamins to meet daily allowances. This includes formula-fed infants and breastfed infants of mothers consuming a diverse and healthy diet. A 2016 survey of dietary intakes in US children up to 48 months of age found that all ages met adequate intake (AI) levels of B vitamins, vitamin C, and vitamin K.¹ Up to half failed to meet the recommended intake of vitamin E, though no adverse effects were noted, suggesting that the appropriate intake of vitamin E for children may need to be reconsidered. The most common dietary supplement in children was vitamin D, which has resulted from concerns regarding insufficient intake in infants and children.¹ The American Academy of Pediatrics (AAP) recommends vitamin D supplementation for all children including adolescents (see the section "Vitamin D," later in this chapter) but otherwise does not recommend multivitamin supplements for healthy children or adolescents.² Nevertheless, intake of multivitamins as a dietary supplement is common, especially in young children. The 2017-2018 National Health and Nutrition Examination Survey (NHANES) demonstrated that 34.6% (95% confidence interval [CI] 28.8%-40.7%) of 2- to 5-year old children in the United States take a multivitamin-mineral supplement.³ The most common reason for taking the supplement was to "improve overall health."⁴ These supplements typically supply 50% of the daily values for both FSVs and WSVs.⁴

Vitamins are commonly used in complementary and integrative medicine in children. This use is unregulated by the US Food and Drug Administration and is controversial. In some cases, such usage is not without harm.⁵ "Therapeutic" uses in pediatrics include autism, asthma, diabetes, and many infectious diseases. Energy drinks and vitamin water products can contain variable amounts of WSVs, including up to 2000% of the recommended intake of vitamin B₆ and more than 8000% of vitamin B₁₂.⁶ A widely-held belief is that, unlike FSVs, WSVs are safe if given in excess; however, WSVs have the potential for serious toxicity if consumed in excessive quantities, in combinations with other medications, or over a prolonged period of time.⁷ Table 20.2 shows tolerable upper intake levels, adverse effects, overdose symptoms, risk factors for symptoms, and drug interactions for FSVs and WSVs.

Table 20.2. Vitamin Tolerable Upper Limits, Adverse Effects/Overdose Symptoms of Toxicity, Overdose Risk Factors, and Drug Interactions

Nutrient	Tolerable Upper Limits	Adverse Effects/Overdose Symptoms	Drug Interactions (Ref ⁵)
Vitamin A (retinol)	0-12 mo 2000 IU/d 1-3 y 2000 IU/d 4-8 y 3000 IU/d 9-13 y 5500 IU/d 14-18 y 10,000 IU/d	Anorexia, increased intracranial pressure, painful bone lesions, hepatotoxicity	Iron, retinoids, hepatotoxic drugs, tetracycline, warfarin
Vitamin D	0-6 mo 1000 IU/d 7-12 mo 1500 IU/d 1-3 y 2500 IU/d 4-8 y 3000 IU/d ≥9 y 4000 IU/d	Hypercalcemia, nephrocalcinosis	Aluminum, calcipotriene, digoxin, magnesium, thiazides, verapamil
Vitamin E	0-12 mo not established 1-3 y 200 mg/d 4-8 y 300 mg/d 9-13 y 600 mg/d 14-18 y 800 mg/d	Toxicity is rare-see text	Aspirin, chemotherapy, ibuprofen, iron, naproxen, warfarin
Vitamin K	Not established	Toxicity is rare-see text	Warfarin
Thiamine (B₁)	Not established, but symptoms can occur with parenteral dosing	Parenteral may cause dermatitis, hypersensitivity, tenderness, tingling, pruritus, pain, weakness, sweating, nausea, gastrointestinal tract distress, restlessness, respiratory distress, pulmonary edema, vascular collapse, death; >10 mg/d × 2 mo, with pantothenic acid, eosinophilic pleuropericardial effusion	High dose >10 mg/d × 2 mo with pantothenic acid; chemotherapy agents
Riboflavin (B₂)	Not established but >400 mg/d suggested	Diarrhea, polyuria, orange urine	Sulfamethoxazole
Niacin (B₃)	0-12 mo unknown 1-3 y unknown 4-8 y 15 mg/d 9-13 y 20 mg/d 14-18 y 30 mg/d	Flushing (niacin flush), pruritus, nausea, headache, vomiting, bloating, diarrhea, anorexia, peptic ulcer, impaired glucose control, impaired uric acid excretion, rare hepatotoxicity	Ibuprofen, insulin, oral diabetes drugs, nonsteroidal antiinflammatory drugs, aspirin, carbamazepine, primidone, valproic acid, clobazam, clonidine, statins, warfarin
Pantothenic Acid (B₅)	Not established	Diarrhea, peripheral sensory neuropathy with paresthesia, high dose with riboflavin, eosinophilic pleuropericardial effusion	High dose >10 mg/d × 2 mo with riboflavin, statins, nicotinic acid
Pyridoxine (B₆)	0-12 mo unknown 1-3 y 30 mg/d 4-8 y 40 mg/d 9-13 y 60 mg/d 14-18 y 80 mg/d	Peripheral sensory neuropathy, nausea, vomiting, somnolence, allergic reactions, breast soreness and enlargement, increased ulcerative colitis; high dose combined with B₁₂, rosacea fulminans	High dose combined with B₁₂, corticosteroids, phenobarbital, phenytoin, levodopa
Biotin (B₇)	Not established	High dose combined with pantothenic acid, eosinophilic pleuropericardial effusion	High dose combined with pantothenic acid
Folate (B₉)	1-3 y 300 mg/d 4-8 y 400 mg/d 9-13 y 600 mg/d 14-18 y 800 mg/d	Abdominal cramps, diarrhea, rash, altered sleep patterns, irritability, confusion, exacerbation of seizures, nausea, flatulence, worsening vitamin B₁₂ deficiency, increased risk of adverse coronary events	Corticosteroids, nonsteroidal antiinflammatory drugs, aspirin, methotrexate, phenobarbital, phenytoin, primidone, pyrimethamine, alcohol, oral contraceptives, trimethoprim
Cobalamin (B₁₂)	Not established	Diarrhea, peripheral vascular thrombosis, itching, urticaria, anaphylaxis; 20 mcg/d, combined with 80 mg/d pyridoxine, may cause rosacea fulminans with nodules, papules, pustules; skin cream with avocado oil may cause itching	20 mcg/d, combined with 80 mg/d pyridoxine; corticosteroids; ibuprofen; antiretroviral drugs; H₂ blockers; proton pump inhibitors
Vitamin C	Children not established Adults 2 g/d	Nausea, vomiting, esophagitis, heartburn, abdominal cramps, gastrointestinal tract obstruction, fatigue, flushing, headache, insomnia, sleepiness, diarrhea, urinary tract stones, increased coronary events	Acetaminophen, aspirin, warfarin, aluminum hydroxide, beta blockers, chemotherapy, estrogens, fluphenazine, protease inhibitors, antiviral drugs, iron

References for the table:

2. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academies Press; 2000

3. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. National Academies Press; 2011

5. Rogovik AL, Vohra S, Goldman RD. Safety considerations and potential interactions of vitamins: should vitamins be considered drugs? Ann Pharmacother. 2010;44(2):311-324

6. Setharaman U. Vitamins. Pediatr Rev. 2006;27(2):44-55

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Introduction