Vitamin B Nutritional Disorders
Updated: Jul 30, 2018
Author: Carrie A Mohila, MD, PhD, FASCP, FCAP; Chief Editor: Adekunle M Adesina, MD, PhD more...
Definition
Most nutritional disorders with deleterious effects on the central and peripheral nervous system are
secondary to vitamin deficiencies, particularly those of the B group. Many of these disorders occur in the
setting of malnutrition associated with alcoholism.
A detailed discussion of all vitamin B deficiencies is beyond the scope of this article. However, four of
the more common vitamin B deficiencies—thiamine (B1), cobalamin (B12), niacin (B3), and folate (B9)
—are reviewed.
Thiamine (vitamin B1)
Thiamine is a water-soluble vitamin required for carbohydrate metabolism. Thiamine diphosphate, the
biologically active form of thiamine, is a required cofactor for pyruvate dehydrogenase and alpha-
ketoglutarate dehydrogenase, two important enzymes in the Krebs cycle, and for transketolase, a key
enzyme involved in the pentose phosphate pathway. Thiamine deficiency results in impaired
carbohydrate and lipid metabolism, altered mitochondrial activity, decreased energy stores, reduced
neurotransmitter synthesis, and altered cellular membrane functions. [1, 2, 3]
Thiamine deficiency can result in disorders that affect both the central and peripheral nervous
systems. Wernicke encephalopathy (WE) is an acute, life-threatening but potentially reversible central
nervous system disorder. If WE is not treated, the condition progresses to Korsakoff syndrome (KS),
with resulting permanent brain damage. Wernicke-Korsakoff syndrome (KWS) has been used to
describe the spectrum of clinical and pathologic changes associated with thiamine deficiency. [4]
Thiamine deficiency can also cause beriberi. Dry beriberi is a peripheral nervous system disorder
associated with peripheral neuropathy. Wet beriberi is a cardiovascular disorder associated with
cardiac manifestations and edema secondary to congestive heart failure. [5] Infantile beriberi can
occur in breastfed infants secondary to inadequate thiamine levels in the mother's breast milk.
Cobalamin (vitamin B12)
Cobalamin is found exclusively in animal products. It is required cofactor for two enzymatic reactions
in humans. Methylcobalamin is required for methionine synthase, which converts homocysteine to
methionine while simultaneously transforming 5’-methyltetrahydrofolate (5-MTHF) to tetrahydrofolate
(THF). Adenosylcobalamin is necessary for methylmalonyl-CoA mutase, which converts
methylmalonyl-CoA to succinyl-CoA within mitochondria. [6, 7]
, Cobalamin deficiency leads to reduced DNA synthesis, altered cell metabolism, and impaired myelin
maintenance. Clinical features of cobalamin deficiency include myelopathy, peripheral neuropathy,
optic neuropathy, glossitis, neuropsychiatric changes, and hematologic manifestations including
megaloblastic anemia. [8]
Niacin (vitamin B3, nicotinic acid)
Niacin is a water-soluble vitamin and an essential component of nicotinamide adenine dinucleotide
(NAD) and nicotinamide adenine dinucleotide phosphate (NADP), coenzymes required for oxidation-
reduction reactions. [9] Niacin can be found in the diet or can be synthesized during tryptophan
metabolism. Niacin deficiency results in pellagra, a condition characterized by diarrhea, dermatitis,
dementia and, eventually, death.
Folate (vitamin B9)
Folate is a water-soluble essential vitamin found in green leafy vegetables and the liver. Folate is
converted into THF, the active form involved in single-carbon transfers in a variety of metabolic
reactions. [10] THF is required for the conversion of homocysteine to methionine (which also requires
cobalamine), the synthesis of thymine and purine bases, and the metabolism of serine and glycine.
Folate deficiency is most commonly associated with megaloblastic anemia. Pregnant women with low
folate intake have an increased risk of neural tube defects (NTDs); folic acid supplementation reduces
the risk of NTDs. [11, 12] In rare cases, folate deficiency may be associated with subacute combined
degeneration of the spinal cord.
Epidemiology
Thiamine (vitamin B1)
The prevalence of Wernicke encephalopathy (WE) in the general population is estimated to be
0.8%-2.8%. [13] In developed countries, WE occurs most frequently in the setting of alcoholism, with
an incidence of up to 12.5%. [1] Up to 80% of patients with WE who survive will progress to Korsakoff
syndrome (KS). [4, 14] Beriberi is rare in Western countries, but it can be seen in alcoholics,
malnourished adults, and pregnant women with hyperemesis gravidarum. [5, 15]
Cobalamin (vitamin B12)
The prevalence of cobalamin deficiency in the United States and the United Kingdom is approximately
6% in those younger than 60 years; in adults older than 60 years, the prevalence is approximately 20%.
African and Asian countries have a much higher prevalence of cobalamin deficiency. [8]
Niacin (vitamin B3, nicotinic acid)
Although endemic pellagra has nearly been eradicated in Western countries due to the fortification of
grains and cereals, [16] niacin deficiency still occurs in setting of alcoholism and malnutrition, even in
developed nations. [17] One autopsy series reported a prevalence of 27% in their cases of chronic
alcoholism. [18]
Updated: Jul 30, 2018
Author: Carrie A Mohila, MD, PhD, FASCP, FCAP; Chief Editor: Adekunle M Adesina, MD, PhD more...
Definition
Most nutritional disorders with deleterious effects on the central and peripheral nervous system are
secondary to vitamin deficiencies, particularly those of the B group. Many of these disorders occur in the
setting of malnutrition associated with alcoholism.
A detailed discussion of all vitamin B deficiencies is beyond the scope of this article. However, four of
the more common vitamin B deficiencies—thiamine (B1), cobalamin (B12), niacin (B3), and folate (B9)
—are reviewed.
Thiamine (vitamin B1)
Thiamine is a water-soluble vitamin required for carbohydrate metabolism. Thiamine diphosphate, the
biologically active form of thiamine, is a required cofactor for pyruvate dehydrogenase and alpha-
ketoglutarate dehydrogenase, two important enzymes in the Krebs cycle, and for transketolase, a key
enzyme involved in the pentose phosphate pathway. Thiamine deficiency results in impaired
carbohydrate and lipid metabolism, altered mitochondrial activity, decreased energy stores, reduced
neurotransmitter synthesis, and altered cellular membrane functions. [1, 2, 3]
Thiamine deficiency can result in disorders that affect both the central and peripheral nervous
systems. Wernicke encephalopathy (WE) is an acute, life-threatening but potentially reversible central
nervous system disorder. If WE is not treated, the condition progresses to Korsakoff syndrome (KS),
with resulting permanent brain damage. Wernicke-Korsakoff syndrome (KWS) has been used to
describe the spectrum of clinical and pathologic changes associated with thiamine deficiency. [4]
Thiamine deficiency can also cause beriberi. Dry beriberi is a peripheral nervous system disorder
associated with peripheral neuropathy. Wet beriberi is a cardiovascular disorder associated with
cardiac manifestations and edema secondary to congestive heart failure. [5] Infantile beriberi can
occur in breastfed infants secondary to inadequate thiamine levels in the mother's breast milk.
Cobalamin (vitamin B12)
Cobalamin is found exclusively in animal products. It is required cofactor for two enzymatic reactions
in humans. Methylcobalamin is required for methionine synthase, which converts homocysteine to
methionine while simultaneously transforming 5’-methyltetrahydrofolate (5-MTHF) to tetrahydrofolate
(THF). Adenosylcobalamin is necessary for methylmalonyl-CoA mutase, which converts
methylmalonyl-CoA to succinyl-CoA within mitochondria. [6, 7]
, Cobalamin deficiency leads to reduced DNA synthesis, altered cell metabolism, and impaired myelin
maintenance. Clinical features of cobalamin deficiency include myelopathy, peripheral neuropathy,
optic neuropathy, glossitis, neuropsychiatric changes, and hematologic manifestations including
megaloblastic anemia. [8]
Niacin (vitamin B3, nicotinic acid)
Niacin is a water-soluble vitamin and an essential component of nicotinamide adenine dinucleotide
(NAD) and nicotinamide adenine dinucleotide phosphate (NADP), coenzymes required for oxidation-
reduction reactions. [9] Niacin can be found in the diet or can be synthesized during tryptophan
metabolism. Niacin deficiency results in pellagra, a condition characterized by diarrhea, dermatitis,
dementia and, eventually, death.
Folate (vitamin B9)
Folate is a water-soluble essential vitamin found in green leafy vegetables and the liver. Folate is
converted into THF, the active form involved in single-carbon transfers in a variety of metabolic
reactions. [10] THF is required for the conversion of homocysteine to methionine (which also requires
cobalamine), the synthesis of thymine and purine bases, and the metabolism of serine and glycine.
Folate deficiency is most commonly associated with megaloblastic anemia. Pregnant women with low
folate intake have an increased risk of neural tube defects (NTDs); folic acid supplementation reduces
the risk of NTDs. [11, 12] In rare cases, folate deficiency may be associated with subacute combined
degeneration of the spinal cord.
Epidemiology
Thiamine (vitamin B1)
The prevalence of Wernicke encephalopathy (WE) in the general population is estimated to be
0.8%-2.8%. [13] In developed countries, WE occurs most frequently in the setting of alcoholism, with
an incidence of up to 12.5%. [1] Up to 80% of patients with WE who survive will progress to Korsakoff
syndrome (KS). [4, 14] Beriberi is rare in Western countries, but it can be seen in alcoholics,
malnourished adults, and pregnant women with hyperemesis gravidarum. [5, 15]
Cobalamin (vitamin B12)
The prevalence of cobalamin deficiency in the United States and the United Kingdom is approximately
6% in those younger than 60 years; in adults older than 60 years, the prevalence is approximately 20%.
African and Asian countries have a much higher prevalence of cobalamin deficiency. [8]
Niacin (vitamin B3, nicotinic acid)
Although endemic pellagra has nearly been eradicated in Western countries due to the fortification of
grains and cereals, [16] niacin deficiency still occurs in setting of alcoholism and malnutrition, even in
developed nations. [17] One autopsy series reported a prevalence of 27% in their cases of chronic
alcoholism. [18]
