Vitamin B-6

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VITAMIN B-6

 

Vitamin B-6 is a water-soluble vitamin that was first isolated in the 1930's.

There are six forms of vitamin B-6: pyridoxal (PL), pyridoxine (PN),

pyridoxamine (PM), and their phosphate derivatives: pyridoxal 5'-phosphate

(PLP), pyridoxine 5'-phosphate (PNP), and pridoxamine 5'-phospate (PNP). PLP

is the active coenzyme form, and has the most importance in human metabolism

(1).

 

FUNCTION

 

Vitamin B-6 is required in the diet because we cannot synthesize it and the

coenzyme, PLP plays a vital role in the function of approximately 100 enzymes

that catalyze essential chemical reactions in the human body (1, 2). For

example, PLP functions as a coenzyme for glycogen phosphorylase, an enzyme

that catalyzes the release of glucose stored in the muscle as glycogen. Much of

the PLP in the human body is found in muscle bound to glycogen phosphorylase.

PLP is also a coenzyme for reactions used to generate glucose from amino acids,

a process known as gluconeogenesis.

 

Nervous system function: The synthesis of the neurotransmitter, serotonin, from

the amino acid, tryptophan, in the brain is catalyzed by a PLP-dependent

enzyme. Other neurotransmitters such as dopamine, norepinephrine and

gamma-aminobutyric acid (GABA) are also synthesized using PLP-dependent enzymes.

 

Red blood cell formation and function: PLP functions as a coenzyme in the

synthesis of heme, a component of hemoglobin. Hemoglobin is found in red blood

cells and is critical to their ability to transport oxygen throughout the body.

Both PL and PLP are able to bind to the hemoglobin molecule and affect its

ability to pick up and release oxygen. However, the impact of this on normal

oxygen delivery to tissues is not known.

 

Niacin formation: The human requirement for another vitamin, niacin (see

Niacin), can be met in part by the conversion of the dietary amino acid,

tryptophan, to niacin, as well as through dietary intake. PLP is a coenzyme

for a critical reaction in the synthesis of niacin from tryptophan. Thus,

adequate vitamin B-6 decreases the requirement for niacin in the diet.

 

Hormone function: Steroid hormones, such as estrogen and testosterone, exert

their effects in the body by binding to steroid hormone receptors in the

nucleus of the cell and altering gene transcription. PLP binds to steroid

receptors in such a manner as to inhibit the binding of steroid hormones, thus

decreasing their effects. The binding of PLP to steroid receptors for

estrogen, progesterone, testosterone, and other steroid hormones suggest that

the vitamin B-6 status of an individual may have implications for diseases

affected by steroid hormones, such as breast cancer and prostate cancer.

 

Nucleic acid synthesis: PLP serves as a coenzyme for a key enzyme involved in

the mobilization of single-carbon functional groups (one-carbon metabolism).

Such reactions are involved in the synthesis of nucleic acids (DNA and RNA).

The effect of B-6 deficiency on immune system function may be partly related to

the role of PLP in one-carbon metabolism (See Prevention).

 

DEFICIENCY

 

Severe deficiency of vitamin B-6 is uncommon. Alcoholics are thought to be most

at risk of vitamin B-6 deficiency, due to a low intake and impaired metabolism

of the vitamin. In the early 1950's seizures were observed in infants as a

result of severe vitamin B-6 deficiency due to an error in the manufacture of

infant formula. Abnormal electroencephalogram (EEG) patterns have been noted in

some studies of vitamin B-6 deficiency. Other neurologic symptoms noted in

severe vitamin B-6 deficiency include irritability, depression, and confusion;

additional symptoms include inflammation of the tongue, sores or ulcers of the

mouth, and ulcers of the skin at the corners of the mouth (1).

 

Because vitamin B-6 is involved in so many aspects of metabolism, several

factors are likely to affect an individual's requirement for vitamin B-6. Of

those factors, protein intake has been studied the most. Increased dietary

protein results in an increased requirement for vitamin B-6 (3), probably

because PLP is a coenzyme for many enzymes involved in amino acid metabolism.

(Amino acids are the building blocks of proteins.) Unlike previous

recommendations, the Food and Nutrition Board (FNB) of the Institute of

Medicine did not express the most recent RDA for vitamin B-6 in terms of

protein intake, although the relationship was considered in setting the RDA (4).

 

The RDA: The current RDA was revised by the FNB in 1998 (4).

 

Men and women between 19 and 50 years of age: 1.3 milligrams (mg) of vitamin

B-6/day.

Men 51 years of age and older: 1.7 mg/day

Women 51 years of age and older: 1.5 mg/day.

 

DISEASE PREVENTION

 

Homocysteine and cardiovascular diseases: Even moderately elevated levels of

homocysteine in the blood have been associated with increased risk for

cardiovascular diseases, such as heart disease and stroke (5). When we digest

protein, amino acids, including methionine, are released. Homocysteine is an

intermediate in the metabolism of methionine. Healthy individuals utilize two

different pathways to metabolize homocysteine. One pathway results in the

conversion of homocysteine back to methionine, and is dependent on folic acid

and vitamin B-12. The other pathway converts homocysteine to another amino

acid, cysteine, and requires two vitamin B-6 (PLP)-dependent enzymes. Thus,

the amount of homocysteine in the blood is regulated by at least three

vitamins: folic acid, vitamin B-12, and vitamin B-6 (See diagram ). Several

large observational studies have demonstrated an association between low

vitamin B-6 intake or status with increased blood homocysteine levels and

increased risk of cardiovascular diseases. A large prospective study found the

risk of heart disease in women who consumed, on average, 4.6 mg of vitamin B-6

daily to be only 67% of the risk in women who consumed an average of 1.1 mg

daily (6). Another large prospective study found higher plasma levels of PLP

to be associated with decreased risk of cardiovascular disease, independent of

homocysteine levels (7). In contrast to folic acid supplementation, studies of

vitamin B-6 supplementation alone have not resulted in significant decreases of

basal (fasting) levels of homocysteine. However, vitamin B-6 supplementation

has been found effective in lowering blood homocysteine levels after an oral

dose of methionine (methionine load test) was given (8), suggesting it may play

a role in the metabolism of homocysteine after meals.

 

Immune function: Low vitamin B-6 intake and status have been associated with

impaired immune function, especially in the elderly. Decreased production of

immune system cells known as lymphocytes, as well as decreased production of an

important immune system protein called interleukin-2, have been measured in

vitamin B-6 deficient individuals. Restoration of adequate vitamin B-6 status

resulted in normalization of the lymphocyte proliferation and interleukin-2

production, suggesting that adequate vitamin B-6 intake is important for

optimal immune system function in older individuals (9, 10). However, one study

found that the amount of vitamin B-6 required to reverse these immune system

impairments in the elderly was 2.9 mg/day for men and 1.9 mg/day for women,

more than the current RDA (9).

 

Cognitive (mental) function: A few recent studies have demonstrated an

association between declines in cognitive function or Alzheimer's disease in

the elderly and inadequate nutritional status of folic acid, vitamin B-12, and

vitamin B-6 and thus, elevated levels of homocysteine (11). One observational

study found higher plasma vitamin B-6 levels to be associated with better

performance on two measures of memory, but unrelated to performance on 18 other

cognitive tests (12). It is presently unclear whether marginal B vitamin

deficiencies, which are relatively common in the elderly, contribute to

age-associated declines in cognitive function or whether both result from

processes associated with aging and/or disease.

 

DISEASE TREATMENT

 

Vitamin B-6 supplements at pharmacologic doses (i.e., doses much larger than

those needed to prevent deficiency) have been used in an attempt to treat a

wide variety of conditions, some of which are discussed below. In general, well

designed, placebo-controlled studies have shown little evidence of benefit from

large supplemental doses of vitamin B-6 (13).

 

Side effects of oral contraceptives: Because vitamin B-6 is required for the

metabolism of the amino acid tryptophan, the tryptophan load test (an assay of

tryptophan metabolites after an oral dose of tryptophan) was used as a

functional assessment of vitamin B-6 status. Abnormal tryptophan load tests in

women taking high-dose oral contraceptives (birth control pills) in the 1960's

and 70's suggested that these women were vitamin B-6 deficient. The abnormal

results in the tryptophan load test led a number of clinicians to prescribe

high doses (100 -150 mg/day) of vitamin B-6 to women in order to relieve

depression and other side effects sometimes experienced with oral

contraceptives. However, most other indices of vitamin B-6 status were normal

in women on high-dose oral contraceptives, and it is likely that the

abnormality in tryptophan metabolism was not due to vitamin B-6 deficiency

(13). A recent study of women on the low-dose oral contraceptives prescribed

currently showed no benefit of up to 150 mg/day of vitamin B-6 (pyridoxine)

over a placebo in the prevention of side effects, such as nausea, vomiting,

dizziness, depression, and irritability (14).

 

Premenstrual syndrome (PMS): The use of vitamin B-6 to relieve the side effects

of high-dose oral contraceptives led to the use of vitamin B-6 in the treatment

of premenstrual syndrome (PMS). PMS refers to a cluster of symptoms, including

but not limited to fatigue, irritability, moodiness/depression, fluid

retention, and breast tenderness, that begin sometime after ovulation

(mid-cycle) and subside with the onset of menstruation (the monthly period). A

review of twelve placebo-controlled double-blind trials of vitamin B-6 in PMS

(15) concluded that evidence for a beneficial effect was weak. A more recent

review of 25 studies of vitamin B-6 and PMS suggested that doses of vitamin B-6

up to 100 mg/day may be of value, but conclusions were limited by the poor

quality of most of the studies evaluated (16). For more information regarding

PMS in general, the National Association for Premenstrual Syndrome (NAPS) in

the U.K. offers information and resources.

 

Depression: Because a key enzyme in the synthesis of the neurotransmitters,

serotonin and norepinephrine, is PLP-dependent, it has been suggested that

vitamin B-6 deficiency may lead to depression. However, clinical trials have

not provided evidence that vitamin B-6 supplementation is effective in the

treatment of depression (13).

 

Morning sickness (nausea and vomiting in pregnancy): Vitamin B-6 has been used

since the 1940's to treat nausea during pregnancy. Vitamin B-6 was included in

the medication, Bendectin, which was prescribed for the treatment of morning

sickness, and later withdrawn from the market due to unproven concerns that it

increased the risk of birth defects. Vitamin B-6 itself is considered safe

during pregnancy, and has been used in pregnant women without any evidence of

fetal harm (17). The results of two double-blind placebo-controlled trials

(25 mg of pyridoxine every 8 hrs for 3 days and 10 mg of pyridoxine every 8 hrs

for 5 days) suggest vitamin B-6 may be beneficial in alleviating morning

sickness. Each study found a slight but significant reduction in nausea or

vomiting in pregnant women. However, it should be noted that morning sickness

also resolves without any treatment, making it difficult to perform

well-controlled trials.

 

Carpal tunnel syndrome: Carpal tunnel syndrome causes numbness, pain, and

weakness of the hand and fingers due to compression of the median nerve at the

wrist. It may result from repetitive stress injury of the wrist or from soft

tissue swelling, which sometimes occurs with pregnancy or hypothyroidism.

Several early studies by the same investigator suggested that vitamin B-6

status was low in individuals with carpal tunnel syndrome and that

supplementation with 100-200 mg/day over several months was beneficial. A

recent study found decreased blood levels of PLP to be associated with

increased pain, tingling, and nocturnal wakening, all symptoms of carpal tunnel

syndrome, in men who were not taking vitamins (18). Studies using

electrophysiological measurements of median nerve conduction have generally

failed to find an association between vitamin B-6 deficiency and carpal tunnel

syndrome. While a few trials have noted some symptomatic relief with vitamin

B-6 supplementation, double-blind placebo-controlled trials have not generally

found vitamin B-6 to be effective in treating carpal tunnel syndrome (13).

 

FOOD SOURCES

 

Surveys in the U.S. have shown that dietary intake of vitamin B-6 averages

about 2 mg/day for men and 1.5 mg/day for women. A survey of elderly

individuals found that men and women over 60 consumed about 1.2 mg/day and 1.0

mg/day, respectively, both less than the current RDA. Certain plant foods

contain a unique form of vitamin B-6 called pyridoxine glucoside. This form of

vitamin B-6 appears to be only about half as bioavailable as vitamin B-6 from

other food sources or supplements. Vitamin B-6 in a mixed diet has been found

to be approximately 75% bioavailable (4). In most cases, including foods in the

diet that are rich in vitamin B-6 should supply enough to prevent deficiency.

However, those who follow a very restricted vegetarian diet might need to

increase their vitamin B-6 intake by eating food, fortified with vitamin B-6,

or by taking a supplement. The vitamin B-6 content of some foods that are

relatively rich in vitamin B-6 is listed below. For more information on the

nutrient content of foods you eat frequently, search the USDA food composition

database.

 

Food

Serving

Vitamin B-6 (mg)

 

Fortified cereal 1 cup 0.5-2.5

 

Banana

1 medium

0.68

Salmon

3 ounces*

0.48

 

Turkey, without skin 3 ounces

0.39

 

Chicken, light meat without skin

3 ounces

0.46

Potato, baked, with skin 1 medium 0.70

Spinach, cooked 1 cup 0.44

Hazelnuts, dry roasted 1 ounce 0.18

Vegetable juice cocktail 6 ounces 0.25

 

*A 3-ounce serving of meat or fish is about the size of a deck of cards.

 

SAFETY

 

Toxicity: Because adverse effects have only been documented from vitamin B-6

supplements and never from food sources, only the supplemental form of vitamin

B-6 (pyridoxine) is discussed with respect to safety. Although vitamin B-6 is

a water-soluble vitamin and is excreted in the urine, very high doses of

pyridoxine over long periods of time may result in painful neurological

symptoms known as sensory neuropathy. Symptoms include pain and numbness of the

extremities, and in severe cases difficulty walking. Sensory neuropathy

typically develops at doses of pyridoxine in excess of 1,000 mg per day.

However, there have been a few case reports of individuals who developed

sensory neuropathies at doses of less than 500 mg daily over a period of

months. None of the studies, in which an objective neurological examination

was performed, found evidence of sensory nerve damage at intakes of pyridoxine

below 200 mg/day (13). In order to prevent sensory neuropathy in virtually all

individuals, the Food and Nutrition Board of the Institute of Medicine set the

tolerable upper intake level (UL) for pyridoxine at 100 mg/day for adults (4).

Because placebo-controlled studies have generally failed to show therapeutic

benefits of high doses of pyridoxine, there is little reason to exceed the UL

of 100 mg/day.

 

Drug interactions: Certain medications, interfere with the metabolism of

vitamin B-6, and may result in deficiency if individuals taking such

medications are not given supplemental vitamin B-6. The anti-tuberculosis

medications, isoniazid and cycloserine, the metal chelator, penicillamine, and

anti-parkinsonian drugs, including L-dopa, form complexes with vitamin B-6,

creating a functional deficiency. The efficacy of other medications may be

altered by high doses of vitamin B-6. High doses of vitamin B-6 have been found

to decrease the efficacy of the anti-convulsants, phenobarbitol and Dilantin,

and L-dopa (2, 13).

 

THE LINUS PAULING INSTITUTE RECOMMENDATION

 

Metabolic studies suggest that young women require 0.02 mg of vitamin B-6 per

gram of protein consumed daily (3, 19). Using the upper boundary for

acceptable levels of protein intake for women (100 grams per day), the daily

requirement for young women would be calculated at 2.0 mg daily. Older adults

may also require at least 2.0 mg/day (see below). For these reasons, the Linus

Pauling Institute recommends that all adults consume at least 2.0 mg of vitamin

B-6 daily. Following the Linus Pauling Institute recommendation to take a daily

multivitamin-mineral supplement containing 100 % of the Daily Value for vitamin

B-6 will ensure an intake of at least 2.0 mg/day of vitamin B-6. Although a

vitamin B-6 intake of 2.0 mg daily is slightly higher than the most recent RDA

(see The RDA), it is 50 times less than the tolerable upper intake level (UL)

set by the Food and Nutrition Board (see Safety).

 

Older adults (65 years and older): Metabolic studies have indicated that the

requirement for vitamin B-6 in older adults is approximately 2.0 mg daily (20),

and could be higher if the effect of marginally deficient intakes of vitamin

B-6 on immune function and homocysteine levels are clarified. Despite evidence

that the requirement for vitamin B-6 may be slightly higher in older adults,

several surveys have found that over half of individuals over age 60 consume

less than the current RDA (1.7 mg/day for men and 1.5 mg/day for women). For

these reasons, the Linus Pauling Institute recommends that older adults take a

multivitamin/multimineral supplement, which generally provides at least 2.0 mg

of vitamin B-6 daily.

 

RECENT RESEARCH

 

Alcohol and Homocysteine: A research letter recently published in the British

medical journal, The Lancet, showed that serum homocysteine levels rose after

consumption of red wine, and gin, but not after beer (21). In a randomized

order, 11 healthy middle-aged men who were moderate drinkers consumed four

glasses of red wine, beer, gin, and mineral water (control) each for 12 weeks

with dinner. Alcohol intake was the same in each of the three alcoholic

beverage periods. At the end of the 12 weeks, blood homocysteine levels

increased about 8% after red wine and gin, but not after beer. PLP levels were

negatively correlated with homocysteine levels in the blood, leading the

investigators to suggest that increased blood levels of vitamin B-6 might

contribute to a lower risk of cardiovascular diseases (see Disease Prevention).

 

Note: Moderate alcohol consumption has been associated with a substantially

lower risk of cardiovascular diseases (22). However, alcohol consumption at the

level used in the above study has also been associated with increased risk of a

number of other health problems including birth defects, liver disease, and an

increased risk of certain types of cancer (e.g., breast cancer) (22,23). The

Linus Pauling Institute does not recommend the consumption of more than 2

alcoholic drinks daily for men and 1 alcoholic drink daily for women.

Moreover, alcohol should be avoided by pregnant women and by individuals with a

personal history or family history of alcoholism, breast cancer or colon

cancer.

 

Vitamin B-6 and kidney stones: A large prospective study published in 1999

examined the relationship between vitamin B-6 intake and the occurrence of

symptomatic kidney stones in women. In a group of more than 85,000 women

without a prior history of kidney stones, followed over fourteen years, those

who consumed 40 mg or more of vitamin B-6 daily had only two thirds the risk of

developing kidney stones compared with those who consumed 3 mg or less (24).

However, in a group of more than 45,000 men followed over six years no

association was found between vitamin B-6 intake and the occurrence of kidney

stones (25). Limited data has shown that supplementation of vitamin B-6 at

levels higher than the tolerable upper intake level (100 mg) decreased elevated

urinary oxalate levels, an important determinant of calcium oxalate kidney

stone formation, in some individuals. However, it is less clear that

supplementation actually resulted in decreased formation of calcium oxalate

kidney stones. Presently, the relationship between vitamin B-6 intake and the

risk of developing kidney stones requires further study before any

recommendation can be made.

 

REFERENCES

 

1. Leklem, J.E. Vitamin B-6. In Machlin, L. Ed. Handbook of Vitamins. New

York: Marcel Decker Inc, 1991: pages 341-378.

 

2. Leklem, J.E. Vitamin B-6. In Shils, M. et al. Eds. Nutrition in Health and

Disease, 9th Edition. Baltimore: Williams & Wilkins, 1999: pages 413-422.

 

3. Hansen, C.M. et al. Vitamin B-6 status of women with a constant intake of

vitamin B-6 changes with three levels of dietary protein. Journal of Nutrition.

1996; volume 126: pages 1891-1901. (PubMed)

 

4. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes:

Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid,

Biotin, and Choline. Washington, DC: National Academy Press, 1998: pages

150-195. (National Academy Press)

 

5. Boushey, C.J. et al. A quantitative assessment of plasma homocysteine as a

risk factor for vascular disease: probable benefits of increasing folic acid

intakes. Journal of the American Medical Association. 1995; volume 274: pages

1049-1057. (PubMed)

 

6. Rimm, E.B. et al. Folate and vitamin B-6 from diet and supplements in

relation to risk of coronary heart disease among women. Journal of the American

Medical Association (JAMA). 1998; volume 279; pages 359-364. (PubMed)

 

7. Folsom, A.R. et al. Prospective study of coronary heart disease incidence

in relation to fasting total homocysteine, related genetic polymorphisms, and B

vitamins: the Atherosclerosis Risk in Communities (ARIC) study. Circulation.

1998; volume 98: pages 204-210. (PubMed)

 

8. Ubbink, J.B. et al. Vitamin requirements for the treatment of

hyperhomocysteinemia in humans. Journal of Nutrition. 1994; volume 124: pages

1927-33. (PubMed)

 

9. Meydani, S.N. et al. Vitamin B-6 deficiency impairs interleukin 2

production and lymphocyte proliferation in elderly adults. American Journal of

Clinical Nutrition. 1991; volume 53: pages 1275-1280. (PubMed)

 

10. Talbott, M.C. et al. Pyridoxine supplementation: effect on lymphocyte

responses in elderly persons. American Journal of Clinical Nutrition. 1987;

volume 46: pages 659-64. (PubMed)

 

11. Selhub, J. et al. B vitamins, homocysteine, and neurocognitive function in

the elderly. American Journal of Clinical Nutrition. 2000; volume 71

(supplement): pages 614S-620S. (PubMed)

 

12. Riggs, K.M. et al. Relations of vitamin B-12, vitamin B-6, folate and

homocysteine to cognitive performance in the Normative Aging Study. American

Journal of Clinical Nutrition. 1996; volume 63: 306-314. (PubMed)

 

13. Bender, D.A. Non-nutritional uses of vitamin B-6. British Journal of

Nutrition. 1999; volume 81: pages 7-20. (PubMed)

 

14. Villegas-Salas E. et al. Effect of vitamin B-6 on the side effects of a

low-dose combined oral contraceptive. Contraception. 1997; volume 55: pages

245-248. (PubMed)

 

15. Kleijen, J. et al. Vitamin B-6 in the treatment of the premenstrual

syndrome--a review. British Journal of Obstetrics and Gynecology. 1990; volume

97: 847-852. (PubMed)

 

16. Wyatt, K.M. et al. Efficacy of vitamin B-6 in the treatment of

premenstrual syndrome: a systematic review. British Medical Journal. 1999;

volume 318: pages 1375-1381. (PubMed)

 

17. Vutyavanich, T. et al. Pyridoxine for nausea and vomiting of pregnancy: a

randomized, double-blind, placebo-controlled trial. American Journal of

Obstetrics and Gynecology. 1995; volume 173: 881-884. (PubMed)

 

18. Keniston, R.C. et al. Vitamin B-6, vitamin C, and capal tunnel syndrome. A

cross-sectional study of 441 adults. Journal of Occupational and Environmental

Medicine. 1997; volume 39: pages 949-959. (PubMed)

 

19. Kretsch, M.J. et al. Vitamin B-6 requirement and status assessment: young

women fed a depletion diet followed by a plant- or animal-protein diet with

graded amounts of vitamin B-6. American Journal of Clinical Nutrition. 1995:

pages 1091-1101. (PubMed)

 

20. Ribaya-Mercado, J.D. et al. Vitamin B-6 requirements of elderly men and

women. Journal of Nutrition. 1991; volume 121: pages 1062-1074. (PubMed)

 

21. van der Gaag, M.S. et al. Effect of consumption of red wine, spirits, and

beer on serum homocysteine. The Lancet. 2000; volume 355: page 1522. (PubMed)

 

22. Thun, M.J. et al. Alcohol consumption and mortality among middle-aged and

elderly U.S. adults. New England Journal of Medicine. 1997; volume 337: pages

1705-1714. (PubMed)

 

23. National Research Council. Diet and health : implications for reducing

chronic disease risk. Washington, D.C. : National Academy Press, 1989.

 

24. Curhan, G.C. et al. Intake of vitamins B-6 and C and the risk of kidney

stones in women. Journal of the American Society of Nephrology. 1999; volume

10: pages 840-845. (PubMed)

 

25. Curhan, G.C. et al. A prospective study of the intake of vitamins C and

B-6, and the risk of kidney stones in men. Journal of Urology. 1996; volume

155: pages 1847-1851. (PubMed)

 

 

--

 

Reviewed by:

James E. Leklem, Ph.D.

Department of Nutrition and Food Management

Oregon State University

 

Last updated 9/11/2000 Copyright 2000 by The Linus Pauling Institute

 

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