Overview of Vitamins: Vitamin Deficiency, Dependency, and Toxicity: Merck Manual Professional

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Vitamin Deficiency, Dependency, and Toxicity

Overview of Vitamins

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Vitamin Deficiency, Dependency, and Toxicity

Overview of Vitamins

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Vitamins may be fat soluble (vitamins A, D, E, and K) or water soluble (B vitamins and vitamin C). The B vitamins include biotin, folate, niacin, pantothenic acid, riboflavin (B₂), thiamin (B₁), B₆ (eg, pyridoxine), and B₁₂ (cobalamins). For dietary requirements, sources, functions, effects of deficiencies and toxicities, blood levels, and usual therapeutic dosages for vitamins, see Table 1: Vitamin Deficiency, Dependency, and Toxicity: Recommended Daily Intakes for Vitamins and Table 2: Vitamin Deficiency, Dependency, and Toxicity: Sources, Functions, and Effects of Vitamins .

Table 1

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Recommended Daily Intakes for Vitamins
Age (yr)	Folate (μg)	NiacinSome Trade Names NIACOR NIASPAN SLO-NIACIN Click for Drug Monograph (mg NE*)	Riboflavin (mg)	Thiamin (mg)	Vitamin A (μg)	Vitamin B₆ (mg)	Vitamin B₁₂ (μg)	Vitamin C (mg)	Vitamin D (IU)^†	Vitamin E (mg)	Vitamin K (μg)
Infants
0–6 mo	65	2	0.3	0.2	400	0.1	0.4	40	400	4	2.0
7–12 mo	80	4	0.4	0.3	500	0.3	0.5	50	400	5	2.5
Children
1–3	150	6	0.5	0.5	300	0.5	0.9	15	600	6	30
4–8	200	8	0.6	0.6	400	0.6	1.2	25	600	7	55
Males
9–13	300	12	0.9	0.9	600	1.0	1.8	45	600	11	60
14–18	400	16	1.3	1.2	900	1.3	2.4	75	600	15	75
19–70	400	16	1.3	1.2	900	1.3	2.4	90	600	15	120
> 70	400	16	1.3	1.2	900	1.7	2.4	90	800 ^‡	15	120
Females
9–13	300	12	0.9	0.9	600	1.0	1.8	45	600	11	60
14–18	400	14	1.0	1.0	700	1.2	2.4	65	600	15	75
19–70	400	14	1.1	1.1	700	1.3	2.4	75	600	15	90
≥ 70	400	14	1.1	1.1	700	1.5	2.4	75	800 ^‡	15	90
Pregnant women
19–50 yr	600	18	1.4	1.4	770	1.9	2.6	85	600	15	90
Breastfeeding women
19–50 yr	500	17	1.6	1.4	1300	2.0	2.8	120	600	19	90
Upper limit (UL)^§
	1000	35	ND	ND	3000	100	ND	2000	4000	1000	ND
Note: Recommended dietary allowances (RDAs) are shown in regular type. RDAs are set to meet the needs of 97 to 98% of healthy people. Adequate intakes (AIs) are shown in bold type. When data to calculate the RDA for a nutrient are insufficient, AIs are based on observed or experimentally determined estimates of nutrient intake by healthy people.
*1 niacinSome Trade Names NIACOR NIASPAN SLO-NIACIN Click for Drug Monograph equivalent (NE) equals 1 mg niacinSome Trade Names NIACOR NIASPAN SLO-NIACIN Click for Drug Monograph or 60 mg dietary tryptophan.
^†200 IU of vitamin D equals 5 μg cholecalciferol.
^‡800 IU of vitamin D is recommended for people ≥ 70 yr.
^§UL is the largest amount of a nutrient that most adults can ingest daily without risk of adverse effects. The more the UL is exceeded, the greater the risk of adverse effects.
ND = not determinable because of lack of data (sources of intake should be limited to foods); RAE = retinol activity equivalents (1 µg RAE of preformed vitamin A= 3.33 IU).
Adapted from Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Washington, DC: National Academy Press.

Recommended Daily Intakes for Vitamins

Age (yr)

Folate (μg)

NiacinSome Trade Names
NIACOR
NIASPAN
SLO-NIACIN
Click for Drug Monograph
(mg NE*)

Riboflavin (mg)

Thiamin (mg)

Vitamin A (μg)

Vitamin B₆ (mg)

Vitamin B₁₂ (μg)

Vitamin C (mg)

Vitamin D (IU)^†

Vitamin E (mg)

Vitamin K (μg)

Infants
0–6 mo	65	2	0.3	0.2	400	0.1	0.4	40	400	4	2.0
7–12 mo	80	4	0.4	0.3	500	0.3	0.5	50	400	5	2.5
Children
1–3	150	6	0.5	0.5	300	0.5	0.9	15	600	6	30
4–8	200	8	0.6	0.6	400	0.6	1.2	25	600	7	55
Males
9–13	300	12	0.9	0.9	600	1.0	1.8	45	600	11	60
14–18	400	16	1.3	1.2	900	1.3	2.4	75	600	15	75
19–70	400	16	1.3	1.2	900	1.3	2.4	90	600	15	120
> 70	400	16	1.3	1.2	900	1.7	2.4	90	800 ^‡	15	120
Females
9–13	300	12	0.9	0.9	600	1.0	1.8	45	600	11	60
14–18	400	14	1.0	1.0	700	1.2	2.4	65	600	15	75
19–70	400	14	1.1	1.1	700	1.3	2.4	75	600	15	90
≥ 70	400	14	1.1	1.1	700	1.5	2.4	75	800 ^‡	15	90
Pregnant women
19–50 yr	600	18	1.4	1.4	770	1.9	2.6	85	600	15	90
Breastfeeding women
19–50 yr	500	17	1.6	1.4	1300	2.0	2.8	120	600	19	90
Upper limit (UL)^§
	1000	35	ND	ND	3000	100	ND	2000	4000	1000	ND
Note: Recommended dietary allowances (RDAs) are shown in regular type. RDAs are set to meet the needs of 97 to 98% of healthy people. Adequate intakes (AIs) are shown in bold type. When data to calculate the RDA for a nutrient are insufficient, AIs are based on observed or experimentally determined estimates of nutrient intake by healthy people.
*1 niacinSome Trade Names NIACOR NIASPAN SLO-NIACIN Click for Drug Monograph equivalent (NE) equals 1 mg niacinSome Trade Names NIACOR NIASPAN SLO-NIACIN Click for Drug Monograph or 60 mg dietary tryptophan.
^†200 IU of vitamin D equals 5 μg cholecalciferol.
^‡800 IU of vitamin D is recommended for people ≥ 70 yr.
^§UL is the largest amount of a nutrient that most adults can ingest daily without risk of adverse effects. The more the UL is exceeded, the greater the risk of adverse effects.
ND = not determinable because of lack of data (sources of intake should be limited to foods); RAE = retinol activity equivalents (1 µg RAE of preformed vitamin A= 3.33 IU).
Adapted from Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Washington, DC: National Academy Press.

Table 2

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Sources, Functions, and Effects of Vitamins
Nutrient	Principal Sources	Functions	Effects of Deficiency and Toxicity
Folate (folic acid)	Fresh green leafy vegetables, fruits, organ meats (eg, liver), enriched cereals and breads	Maturation of RBCs Synthesis of purines, pyrimidines, and methionine Development of fetal nervous system	Deficiency: Megaloblastic anemia, neural tube birth defects, mental confusion
NiacinSome Trade Names NIACOR NIASPAN SLO-NIACIN Click for Drug Monograph (nicotinic acid, nicotinamide)	Liver, red meat, fish, poultry, legumes, whole-grain or enriched cereals and breads	Oxidation-reduction reactions Carbohydrate and cell metabolism	Deficiency: Pellagra (dermatitis, glossitis, GI and CNS dysfunction) Toxicity: Flushing
Riboflavin (vitamin B₂)	Milk, cheese, liver, meat, eggs, enriched cereal products	Many aspects of carbohydrate and protein metabolism Integrity of mucous membranes	Deficiency: Cheilosis, angular stomatitis, corneal vascularization
Thiamin (vitamin B₁)	Whole grains, meat (especially pork and liver), enriched cereal products, nuts, legumes, potatoes	Carbohydrate, fat, amino acid, glucose, and alcohol metabolism Central and peripheral nerve cell function Myocardial function	Deficiency: Beriberi (peripheral neuropathy, heart failure), Wernicke-Korsakoff syndrome
Vitamin A (retinol)	As preformed vitamin: fish liver oils, liver, egg yolks, butter, vitamin A–fortified dairy products As provitamin carotenoids: dark green and yellow vegetables, carrots, yellow and orange fruits	Formation of rhodopsin (a photoreceptor pigment in the retina) Integrity of epithelia Lysosome stability Glycoprotein synthesis	Deficiency: Night blindness, perifollicular hyperkeratosis, xerophthalmia, keratomalacia, increased morbidity and mortality in young children Toxicity: Headache, peeling of skin, hepatosplenomegaly, bone thickening, intracranial hypertension, papilledema
Vitamin B₆ group (pyridoxine, pyridoxal, pyridoxamine)	Organ meats (eg, liver) whole-grain cereals, fish, legumes	Many aspects of nitrogen metabolism (eg, transaminations, porphyrin and heme synthesis, tryptophan conversion to niacinSome Trade Names NIACOR NIASPAN SLO-NIACIN Click for Drug Monograph ) Nucleic acid biosynthesis Fatty acid, lipid, and amino acid metabolism	Deficiency: Seizures, anemia, neuropathies, seborrheic dermatitis Toxicity: Peripheral neuropathy
Vitamin B₁₂ (cobalamins)	Meats (especially beef, pork, and organ meats [eg, liver]), poultry, eggs, fortified cereals, milk and milk products	Maturation of RBCs, neural function, DNA synthesis, myelin synthesis and repair	Deficiency: Megaloblastic anemia, neurologic deficits (confusion, paresthesias, ataxia)
Vitamin C (ascorbic acid)	Citrus fruits, tomatoes, potatoes, broccoli, strawberries, sweet peppers	Collagen formation Bone and blood vessel health Carnitine, hormone, and amino acid formation Wound healing	Deficiency: Scurvy (hemorrhages, loose teeth, gingivitis, bone defects)
Vitamin D (cholecalciferol, ergocalciferolSome Trade Names DRISDOL Click for Drug Monograph )	Direct ultraviolet B irradiation of the skin (main source), fortified dairy products (main dietary source), fish liver oils, fatty fish, liver	Ca and phosphate absorption Mineralization and repair of bone Tubular reabsorption of Ca InsulinSome Trade Names HUMULIN NOVOLIN Click for Drug Monograph and thyroid function, improvement of immune function, reduction of autoimmune disease	Deficiency: Rickets (sometimes with tetany), osteomalacia Toxicity: Hypercalcemia, anorexia, renal failure, metastatic calcifications
Vitamin E group (α-tocopherol, other tocopherols)	Vegetable oils, nuts, legumes	Intracellular antioxidant Scavenger of free radicals in biologic membranes	Deficiency: RBC hemolysis, neurologic deficits Toxicity: Tendency to bleed
Vitamin K group (phylloquinone, menaquinones)	Green leafy vegetables (especially collards, spinach, and salad greens), soy beans, vegetable oils Bacteria in the GI tract after neonatal period	Formation of prothrombin, other coagulation factors, and bone proteins	Deficiency: Bleeding due to deficiency of prothrombin and other factors, osteopenia

Sources, Functions, and Effects of Vitamins

Nutrient

Principal Sources

Functions

Effects of Deficiency and Toxicity

Folate (folic acid)	Fresh green leafy vegetables, fruits, organ meats (eg, liver), enriched cereals and breads	Maturation of RBCs Synthesis of purines, pyrimidines, and methionine Development of fetal nervous system	Deficiency: Megaloblastic anemia, neural tube birth defects, mental confusion
NiacinSome Trade Names NIACOR NIASPAN SLO-NIACIN Click for Drug Monograph (nicotinic acid, nicotinamide)	Liver, red meat, fish, poultry, legumes, whole-grain or enriched cereals and breads	Oxidation-reduction reactions Carbohydrate and cell metabolism	Deficiency: Pellagra (dermatitis, glossitis, GI and CNS dysfunction) Toxicity: Flushing
Riboflavin (vitamin B₂)	Milk, cheese, liver, meat, eggs, enriched cereal products	Many aspects of carbohydrate and protein metabolism Integrity of mucous membranes	Deficiency: Cheilosis, angular stomatitis, corneal vascularization
Thiamin (vitamin B₁)	Whole grains, meat (especially pork and liver), enriched cereal products, nuts, legumes, potatoes	Carbohydrate, fat, amino acid, glucose, and alcohol metabolism Central and peripheral nerve cell function Myocardial function	Deficiency: Beriberi (peripheral neuropathy, heart failure), Wernicke-Korsakoff syndrome
Vitamin A (retinol)	As preformed vitamin: fish liver oils, liver, egg yolks, butter, vitamin A–fortified dairy products As provitamin carotenoids: dark green and yellow vegetables, carrots, yellow and orange fruits	Formation of rhodopsin (a photoreceptor pigment in the retina) Integrity of epithelia Lysosome stability Glycoprotein synthesis	Deficiency: Night blindness, perifollicular hyperkeratosis, xerophthalmia, keratomalacia, increased morbidity and mortality in young children Toxicity: Headache, peeling of skin, hepatosplenomegaly, bone thickening, intracranial hypertension, papilledema
Vitamin B₆ group (pyridoxine, pyridoxal, pyridoxamine)	Organ meats (eg, liver) whole-grain cereals, fish, legumes	Many aspects of nitrogen metabolism (eg, transaminations, porphyrin and heme synthesis, tryptophan conversion to niacinSome Trade Names NIACOR NIASPAN SLO-NIACIN Click for Drug Monograph ) Nucleic acid biosynthesis Fatty acid, lipid, and amino acid metabolism	Deficiency: Seizures, anemia, neuropathies, seborrheic dermatitis Toxicity: Peripheral neuropathy
Vitamin B₁₂ (cobalamins)	Meats (especially beef, pork, and organ meats [eg, liver]), poultry, eggs, fortified cereals, milk and milk products	Maturation of RBCs, neural function, DNA synthesis, myelin synthesis and repair	Deficiency: Megaloblastic anemia, neurologic deficits (confusion, paresthesias, ataxia)
Vitamin C (ascorbic acid)	Citrus fruits, tomatoes, potatoes, broccoli, strawberries, sweet peppers	Collagen formation Bone and blood vessel health Carnitine, hormone, and amino acid formation Wound healing	Deficiency: Scurvy (hemorrhages, loose teeth, gingivitis, bone defects)
Vitamin D (cholecalciferol, ergocalciferolSome Trade Names DRISDOL Click for Drug Monograph )	Direct ultraviolet B irradiation of the skin (main source), fortified dairy products (main dietary source), fish liver oils, fatty fish, liver	Ca and phosphate absorption Mineralization and repair of bone Tubular reabsorption of Ca InsulinSome Trade Names HUMULIN NOVOLIN Click for Drug Monograph and thyroid function, improvement of immune function, reduction of autoimmune disease	Deficiency: Rickets (sometimes with tetany), osteomalacia Toxicity: Hypercalcemia, anorexia, renal failure, metastatic calcifications
Vitamin E group (α-tocopherol, other tocopherols)	Vegetable oils, nuts, legumes	Intracellular antioxidant Scavenger of free radicals in biologic membranes	Deficiency: RBC hemolysis, neurologic deficits Toxicity: Tendency to bleed
Vitamin K group (phylloquinone, menaquinones)	Green leafy vegetables (especially collards, spinach, and salad greens), soy beans, vegetable oils Bacteria in the GI tract after neonatal period	Formation of prothrombin, other coagulation factors, and bone proteins	Deficiency: Bleeding due to deficiency of prothrombin and other factors, osteopenia

Table 3

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Potential Vitamin-Drug Interactions
Nutrient	Drug
Biotin	Antibiotics, anticonvulsants
Folate	Alcohol, 5-fluorouracilSome Trade Names ADRUCIL Click for Drug Monograph , metforminSome Trade Names GLUCOPHAGE Click for Drug Monograph , methotrexateSome Trade Names RHEUMATREX Click for Drug Monograph , oral contraceptives, anticonvulsants (eg, phenobarbitalSome Trade Names LUMINAL Click for Drug Monograph , phenytoinSome Trade Names DILANTIN Click for Drug Monograph , primidoneSome Trade Names MYSOLINE Click for Drug Monograph ), sulfasalazineSome Trade Names AZULFIDINE Click for Drug Monograph , triamtereneSome Trade Names DYRENIUM Click for Drug Monograph , trimethoprimSome Trade Names PROLOPRIM TRIMPEX Click for Drug Monograph
Niacin	Alcohol, isoniazidSome Trade Names INH NYDRAZID Click for Drug Monograph
Riboflavin	Alcohol, barbiturates, phenothiazines, thiazide diuretics, tricyclic antidepressants
Thiamin	Alcohol; oral contraceptives; thiamin antagonists in coffee, tea, raw fish, and red cabbage
Vitamin A	CholestyramineSome Trade Names QUESTRAN Click for Drug Monograph , mineral oil
Vitamin B₆	Alcohol, anticonvulsants, corticosteroids, cycloserineSome Trade Names SEROMYCIN Click for Drug Monograph , hydralazineSome Trade Names APRESOLINE Click for Drug Monograph , isoniazidSome Trade Names INH NYDRAZID Click for Drug Monograph , levodopa, oral contraceptives, penicillamineSome Trade Names CUPRIMINE Click for Drug Monograph
Vitamin B₁₂	Antacids, metforminSome Trade Names GLUCOPHAGE Click for Drug Monograph , nitrous oxide (repeated exposure)
Vitamin C	Corticosteroids
Vitamin D	Antipsychotics, corticosteroids, mineral oil, anticonvulsants (eg, phenobarbitol, phenytoinSome Trade Names DILANTIN Click for Drug Monograph , primidoneSome Trade Names MYSOLINE Click for Drug Monograph ), rifampinSome Trade Names RIFADIN RIMACTANE Click for Drug Monograph
Vitamin E	Mineral oil, warfarinSome Trade Names COUMADIN Click for Drug Monograph
Vitamin K	Antibiotics, anticonvulsants, mineral oil, rifampinSome Trade Names RIFADIN RIMACTANE Click for Drug Monograph , warfarinSome Trade Names COUMADIN Click for Drug Monograph

Potential Vitamin-Drug Interactions

Nutrient

Drug

Biotin	Antibiotics, anticonvulsants
Folate	Alcohol, 5-fluorouracilSome Trade Names ADRUCIL Click for Drug Monograph , metforminSome Trade Names GLUCOPHAGE Click for Drug Monograph , methotrexateSome Trade Names RHEUMATREX Click for Drug Monograph , oral contraceptives, anticonvulsants (eg, phenobarbitalSome Trade Names LUMINAL Click for Drug Monograph , phenytoinSome Trade Names DILANTIN Click for Drug Monograph , primidoneSome Trade Names MYSOLINE Click for Drug Monograph ), sulfasalazineSome Trade Names AZULFIDINE Click for Drug Monograph , triamtereneSome Trade Names DYRENIUM Click for Drug Monograph , trimethoprimSome Trade Names PROLOPRIM TRIMPEX Click for Drug Monograph
Niacin	Alcohol, isoniazidSome Trade Names INH NYDRAZID Click for Drug Monograph
Riboflavin	Alcohol, barbiturates, phenothiazines, thiazide diuretics, tricyclic antidepressants
Thiamin	Alcohol; oral contraceptives; thiamin antagonists in coffee, tea, raw fish, and red cabbage
Vitamin A	CholestyramineSome Trade Names QUESTRAN Click for Drug Monograph , mineral oil
Vitamin B₆	Alcohol, anticonvulsants, corticosteroids, cycloserineSome Trade Names SEROMYCIN Click for Drug Monograph , hydralazineSome Trade Names APRESOLINE Click for Drug Monograph , isoniazidSome Trade Names INH NYDRAZID Click for Drug Monograph , levodopa, oral contraceptives, penicillamineSome Trade Names CUPRIMINE Click for Drug Monograph
Vitamin B₁₂	Antacids, metforminSome Trade Names GLUCOPHAGE Click for Drug Monograph , nitrous oxide (repeated exposure)
Vitamin C	Corticosteroids
Vitamin D	Antipsychotics, corticosteroids, mineral oil, anticonvulsants (eg, phenobarbitol, phenytoinSome Trade Names DILANTIN Click for Drug Monograph , primidoneSome Trade Names MYSOLINE Click for Drug Monograph ), rifampinSome Trade Names RIFADIN RIMACTANE Click for Drug Monograph
Vitamin E	Mineral oil, warfarinSome Trade Names COUMADIN Click for Drug Monograph
Vitamin K	Antibiotics, anticonvulsants, mineral oil, rifampinSome Trade Names RIFADIN RIMACTANE Click for Drug Monograph , warfarinSome Trade Names COUMADIN Click for Drug Monograph

Dietary requirements for vitamins (and other nutrients) are expressed as daily recommended intake (DRI). There are 3 types of DRI:

Recommended daily allowance (RDA): RDAs are set to meet the needs of 97 to 98% of healthy people.
Adequate intake (AI): When data to calculate an RDA are insufficient, AIs are based on observed or experimentally determined estimates of nutrient intake by healthy people.
Tolerable upper intake level (UL): ULs are the largest amount of a nutrient that most adults can ingest daily without risk of adverse health effects.

In developed countries, vitamin deficiencies result mainly from poverty, food faddism, drugs (see Nutrition: General Considerations: Nutrient-Drug Interactions and Table 3: Vitamin Deficiency, Dependency, and Toxicity: Potential Vitamin-Drug Interactions), alcoholism, or prolonged and inadequately supplemented parenteral feeding. Mild vitamin deficiency is common among frail and institutionalized elderly people who have protein-energy undernutrition. In developing countries, deficiencies can result from lack of access to nutrients. Deficiencies of water-soluble vitamins (except vitamin B₁₂) may develop after weeks to months of undernutrition. Deficiencies of fat-soluble vitamins and of vitamin B₁₂ take > 1 yr to develop because the body stores them in relatively large amounts. Intakes of vitamins sufficient to prevent classic vitamin deficiencies (such as scurvy or beriberi) may not be adequate for optimum health. This area remains one of controversy and active research.

Vitamin dependency results from a genetic defect involving metabolism of a vitamin. In some cases, vitamin doses as high as 1000 times the DRI improve function of the altered metabolic pathway.

Vitamin toxicity (hypervitaminosis) usually results from taking megadoses of vitamin A, D, C, B₆, or niacin.

Because many people eat irregularly, foods alone may provide suboptimal amounts of some vitamins. In these cases, the risk of certain cancers or other disorders may be increased. However, routine daily multivitamin supplements have not been proved to reduce cancer.

Last full review/revision December 2012 by Larry E. Johnson, MD, PhD

Content last modified January 2013

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