General Considerations of B-complex Vitamins

Reference from the joint venture of FAO/WHO expert consultation on Human Vitamins and Minerals verbatim. (Chapter 3)

General considerations for B-complex vitamins

Notes on suggested recommendations

6. Food and Nutrition Board, Institute of Medicine/National Academy of Sciences-National Research Council. 1998. Dietary Reference Intake: Folate, Other B Vitamins, and Choline. Washington, D.C., National Academy Press.

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Reference from the joint report of FAO/WHO expert consultation on Human Vitamins and Minerals verbatim. (Chapter 3)

Biotin

Background with requisite function in human metabolic processes

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Reference from the joint report of FAO/WHO expert consultation of Human Vitamins and Minerals verbatim. (Chapter 3)

Pantothenate

Background with requisite function in human metabolic processes

Deficiency

8. McCormick, D.B. 1997. Vitamin, Structure and Function of. In: Encyclopedia of Molecular Biology and Molecular Medicine, Vol. 6. Meyers, R.A., ed. Weinheim: VCH, p. 244-52.

9. McCormick, D.B & Greene, H.L. 1994. Vitamins. In: Tietz Textbook of Clin Chem., 2nd edition. Burtis, V.A., Ashwood, E.R., eds. Philadelphia: W.B. Saunders, p. 1275-1316.

100. McCormick, D.B. 1988. Pantothenic Acid. In: Modern Nutrition in Health and Disease, 6th edition. p.383-7. Shils, M.E., Young, V.R., eds. Philadelphia: Lea & Febiger.

101. Plesofsky-Vig, N. 1994. Pantothenic acid and co-enzyme A. In: Modern Nutrition in Health and Disease, 8th edition. Shils, M.E., Olson, J.A., Shike, M., eds. Philadelphia, Lea

& Febiger, p. 395-401.

The widespread occurrence of releasable pantothenic acid in food makes a dietary deficiency unlikely (8, 9, 100, 101). If a deficiency occurs, it is usually accompanied by deficits of other nutrients. 

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Reference from the joint report of FAO/WHO expert consultation of Human Vitamins and Minerals verbatim. (Chapter 3)

Vitamin B6

Background with requisite function in human metabolic processes

Deficiency

72. McCormick, D.B. 1988. Vitamin B6. In: Modern Nutrition in Health and Disease, 6th edition. Shils, M.E., Young, V.R., eds. Philadelphia: Lea & Febiger, p. 376-82.

A deficiency of vitamin B6 alone is uncommon because it usually occurs in association with a deficit in other B-complex vitamins (72). Early biochemical changes include decreased levels of plasma PLP and urinary 4-pyridoxic acid. These are followed by decreases in synthesis of transaminases (aminotransferases) and other enzymes of amino acid metabolism such that there is an increased urinary xanthurenate and a decreased glutamate conversion to the antineurotransmitter γ-aminobutyrate.

Thiamin, Riboflavin, Niacin, Vitamin B6, Pantothenic Acid and Biotin...continued #3.

Reference from the joint report of FAO/WHO expert consultation on Human Vitamins and Minerals verbatim. (Chapter 3)

Niacin

Background with requisite function in human metabolic processes

Deficiency

8. McCormick, D.B. 1997. Vitamin, Structure and Function of. In: Encyclopedia of Molecular Biology and Molecular Medicine, Vol. 6. Meyers, R.A., ed. Weinheim: VCH, p. 244-52.

9. McCormick, D.B & Greene, H.L. 1994. Vitamins. In: Tietz Textbook of Clin Chem., 2nd edition. Burtis, V.A., Ashwood, E.R., eds. Philadelphia: W.B. Saunders, p. 1275-1316.

61. McCormick, D.B. 1988. Niacin. In: Modern Nutrition in Health and Disease, 6th edition. Shils, M.E., Young, V.R., eds. Philadelphia: Lea & Febiger, 370-5.

Niacin (nicotinic acid) deficiency classically results in pellagra, which is a chronic wasting disease associated with a characteristic erythematous dermatitis that is bilateral an symmetrical, a dementia after mental changes including insomnia and apathy preceding an overt encephalopathy, and diarrhoea resulting from inflammation of the intestinal mucous surfaces (8, 9, 61).

Population at Risk for Vitamin B12 Deficiency

Populations at risk for and consequences of vitamin B12 deficiency

Vegetarians

Because plants do not synthesise vitamin B12, individuals who consume diets completely free of animal products (vegan diets) are at risk of vitamin B12 deficiency. This is not true of lactoovo-vegetarians, who consume the vitamin in eggs, milk, and other dairy products.

Role of Vitamin B12 in Human Metabolic Processes

Role of vitamin B12 in human metabolic processes

Although the nutritional literature still uses the term vitamin B12, a more specific name for vitamin B12 is cobalamin. Vitamin B12 is the largest of the B complex vitamins, with a molecular weight of over 1000. It consists of a corrin ring made up of four pyrroles with cobalt at the center of the ring. There are several vitamin B12–dependent enzymes in bacteria and algae, but no species of plants have the enzymes necessary for vitamin B12 synthesis. This fact has significant implications for the dietary sources and availability of vitamin B12. In mammalian cells there are only two vitamin B12–dependent enzymes. 

One of these enzymes, methionine synthase, uses the chemical form of the vitamin which has a methyl group attached to the cobalt and is called methylcobalamin. The other enzyme, methylmalonyl CoA mutase, uses vitamin B12 with a 5’-adeoxyadenosyl moiety attached to the cobalt and is called 5’-deoxyaldenosylcobalamin, or coenzyme B12. In nature there are two other forms of vitamin B12: hydroxycobalamin and aquacobalamin, where hydroxyl and water groups, respectively, are attached to the cobalt. The synthetic form of vitamin B12 found in supplements and fortified foods is cyanocobalamin, which has cyanide attached to the cobalt. These three forms of B12 are enzymatically activated to the methyl- or deoxyadenosylcobalamins in all mammalian cells.

Riboflavin

Factors affecting requirements

Several studies reported modest effects of physical activity on the erythrocyte glutathione reductase AC. A slight increase in the AC and decrease in urinary flavin of weightreducing women and older women undergoing exercise training were “normalised” with 20 percent additional riboflavin. However, riboflavin supplementation did not lead to an increase in work performance when such subjects were not clinically deficient.

Assessment of Vitamin B12 Status

Traditionally it was thought that low vitamin B12 status was accompanied by a low serum or plasma vitamin B12. Recently this has been challenged by Lindenbaum et al.,who suggested that a proportion of people with normal vitamin B12 levels are in fact vitamin B12 deficient. They also suggested that elevation of plasma homo-cysteine and plasma MMA are more sensitive indicators of vitamin B12 status. Although plasma homo-cysteine may also be elevated because of folate or vitamin B6 deficiency, elevation of MMA apparently always occurs with poor vitamin B12 status. There may be other reasons why MMA is elevated, such as renal insufficiency, so the elevation of itself is not diagnostic. Many would feel that low or decreased plasma vitamin B12 levels should be the first indication of poor status and that this could be confirmed by an elevated MMA if this assay was available.

Vitamin B12 Interaction with Folate or Folic Acid

One of the vitamin B12 – dependent enzymes, methionine synthase, functions in one of the two folate cycles – the methylation cycle. This cycle is necessary to maintain availability of the methyl donor S-adenosylmethionine; interruption reduces the wide range of methylated products. One such important methylation is that of myelin basic protein. Reductions in the level of S-adenosylmethionine seen in PA and other causes of vitamin B12 deficiency produce demyelination of the peripheral nerves and the spinal column, called subacute combined degeneration. This neuropathy is one of the main presenting conditions in PA. The other principal presenting condition in PA is a megaloblastic anaemia morphologically identical to that seen in folate deficiency. Disruption of the methylation cycle should cause a lack of DNA biosynthesis and anaemia.

Atrophic Gastritis

Atrophic gastritis

Historically, PA was considered to be the major cause of vitamin B12 deficiency, but it was a fairly rare condition, perhaps affecting 1 percent to a few percent of elderly populations. More recently it has been suggested that a far more common problem is that of hypochlorhydria associated with atrophic gastritis, where there is a progressive reduction with age of the ability of the parietal cells to secrete hydrochloric acid. 

Pernicous Anemia

Pernicious anaemia - Malabsorption of vitamin B12 can occur at several points during digestion. By far the most important condition resulting in vitamin B12 malabsorption is the auto-immune disease called pernicious anaemia (PA). In most cases of PA, antibodies are produced against the parietal cells causing them to atrophy, lose their ability to produce intrinsic factor, and secrete hydrochloric acid. In some forms of PA the parietal cells remain intact but auto-antiobodies are produced against the intrinsic factor itself and attach to it, thus preventing it from binding vitamin B12. In another less common form of PA, the antibodies allow vitamin B12 to bind to the intrinsic factor but prevent the absorption of the intrinsic factor–vitamin B12 complex by the ileal receptors. As is the case with most auto-immune diseases, the incidence of PA increases markedly with age. 

Vitamin B12

Role of vitamin B12 in human metabolic processes

Although the nutritional literature still uses the term vitamin B12, a more specific name for vitamin B12 is cobalamin. Vitamin B12 is the largest of the B complex vitamins, with a molecular weight of over 1000. It consists of a corrin ring made up of four pyrroles with cobalt at the center of the ring. 

Dietary Sources of Water-Soluble Vitamins

Foods that are listed according to the concentrations of vitamin which they contain.

Thiamin (B1) - Pork, organ meats, whole grains, and legumes

Riboflavin (B2) - Milk and dairy products, meats, and green vegetables

Niacin (nicotinic acid and nicotinamide) - Liver, lean meats, grains, and legumes; can be formed from tryptophan

Vitamin B6 (pyridoxine, pyridoxamine, and pyridoxal) - Meats, vegetables, and whole-grain cereals

Pantothenic acid  - Animal tissues, whole-grain cereals, and legumes; widely distributed

Biotin - Liver, yeast, egg, yolk, soy flour, and cereals

Biotin

Background with requisite function in human metabolic processes

Deficiency

Biotin deficiency in humans has been clearly documented with prolonged consumption of raw egg whites, which contain biotin-binding avidin. Biotin deficiency was also observed in cases of parenteral nutrition with solutions lacking biotin given to patients with short-gut syndrome and other causes of malabsorption. Some cases of biotin deficiency were noted in infants with intractable diaper dermatitis and in those fed special formulas. Dietary deficiency in otherwise normal people is probably rare. Some patients have multiple carboxylase deficiencies and there are occasional biotinidase deficiencies. Clinical signs of deficiency include dermatitis of an erythematous and seborrheic type; conjunctivitis; alopecia; and central nervous system abnormalities such as hypotonia, lethargy, and developmental delay in infants and depression, hallucinations, and paresthesia of the extremities in adults.

Pantothenate

Background with requisite function in human metabolic processes

Deficiency

The widespread occurrence of releasable pantothenic acid in food makes a dietary deficiency unlikely. If a deficiency occurs, it is usually accompanied by deficits of other nutrients. The use of experimental animals, an antagonistic analogue (ω-methyl-pantothenate) given to humans, and more recently the feeding of semi-synthetic diets virtually free of pantothenate have all helped to define signs and symptoms of deficiency. Subjects become irascible; develop postural hypotension, rapid heart rate on exertion, epigastric distress with anorexia and constipation, numbness and tingling of the hands and feet ("burning feet" syndrome); and have hyperactive deep tendon reflexes and weakness of finger extensor muscles. Some cases of pantothenate deficiency have been observed in patients with acne and other dermatitic conditions.

Vitamin B6

Background with requisite function in human metabolic processes

Deficiency

A deficiency of vitamin B6 alone is uncommon because it usually occurs in association with a deficit in other B-complex vitamins. Early biochemical changes include decreased levels of plasma PLP and urinary 4-pyridoxic acid. These are followed by decreases in synthesis of transaminases (aminotransferases) and other enzymes of amino acid metabolism such that there is an increased urinary xanthurenate and a decreased glutamate conversion to the antineurotransmitter γ-aminobutyrate. 

Hypovitaminosis B6 may often occur with riboflavin deficiency, because riboflavin is needed for the formation of the co-enzyme PLP. Infants are especially susceptible to insufficient intakes, which can lead to epileptiform convulsions. Skin changes include dermatitis with cheilosis and glossitis. There is usually a decrease in circulating lymphocytes and possibly a normocytic, microcytic, or sideroblastic anaemia. The sensitivity of such systems as sulphur amino acid metabolism to vitamin B6 availability is reflected in homo-cysteinemia. A decrease in the metabolism of glutamate in the brain, which is found in vitamin B6 insufficiency, reflects a nervous system dysfunction. As is the case with other micronutrient deficiencies, vitamin B6 deficiency results in an impairment of the immune system. A current concern is for the rather pandemic occurrence of somewhat low vitamin B6 intakes in many people who eat poorly (e.g., people with eating disorders). Vitamin B6 deficiency has also been observed in Russian schoolchildren (Moscow), Southeast Asian schoolchildren (infected with hookworm), elderly Europeans (Dutch), and in some individuals with hyperhomo-cysteinemia or on chronic hemodialysis. Several medical conditions can also affect vitamin B6 metabolism and lead to deficiency symptoms.

Niacin

Deficiency

Niacin (nicotinic acid) deficiency classically results in pellagra, which is a chronic wasting disease associated with a characteristic erythematous dermatitis that is bilateral and symmetrical, a dementia after mental changes including insomnia and apathy preceding an overt encephalopathy, and diarrhoea resulting from inflammation of the intestinal mucous surfaces. At present, pellagra occurs endemically in poorer areas. Its cause has been mainly attributed to a deficiency of niacin; however, its biochemical inter-relationship to riboflavin and vitamin B6, which are needed for the conversion of L-tryptophan to niacin equivalents (NEs), suggests that insufficiencies of these vitamins may also contribute to pellagra. Pellagra-like syndromes occurring in the absence of a dietary niacin deficiency are also attributable to disturbances in tryptophan metabolism (e.g., Hartnup disease with impaired absorption of the amino acid and carcinoid syndrome where the major catabolic pathway routes to 5-hydroxytryptophan). Pellagra also occurs in people with chronic alcoholism. Cases of niacin deficiency have been found in people suffering from Crohn’s disease.

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Reference from the joint report of FAO/WHO expert consultation on Human Vitamins and Minerals verbatim. (Chapter 3)

Riboflavin

Background with requisite function in human metabolic processes.

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Reference from the joint report of FAO/WHO expert consultation on Human Vitamins and Minerals verbatim. (Chapter 3)

Biochemical Indicators

Indicators used to estimate thiamin requirements are urinary excretion, erythrocyte transketolase activity coefficient, erythrocyte thiamin, blood pyruvate and lactate, and neurologic changes. The excretion rate of the vitamin and its metabolites reflects intake, and the validity of the assessment of thiamin nutriture is improved with load test.