what is vitamin b complex used for

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Vitamin B6

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Vitamin B6

Vitamin B6 is a water-soluble vitamin that was first isolated in the
1930s. There are three traditionally considered forms of vitamin B6:
pyridoxal (PL), pyridoxine (PN), pyridoxamine (PM). The phosphate
ester derivative pyridoxal 5'-phosphate (PLP) is the principal
coenzyme form and has the most importance in human metabolism (1-3).

Function

Vitamin B6 must be obtained from the diet because humans cannot
synthesize it. PLP plays a vital role in the function of approximately
100 enzymes that catalyze essential chemical reactions in the human
body (1-5). For example, PLP functions as a coenzyme for glycogen
phosphorylase, an enzyme that catalyzes the release of glucose from
stored 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 (4, 5).

Nervous system function

In the brain, the synthesis of the neurotransmitter, serotonin, from
the amino acid, tryptophan, 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 (4).

Red blood cell formation and function

PLP functions as a coenzyme in the synthesis of heme, an
iron-containing 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 (4).

Niacin formation

The human requirement for another B vitamin, niacin, can be met in
part by the conversion of the essential 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 B6 decreases the requirement for dietary niacin (4).

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 a manner that inhibits the binding of steroid
hormones, thus decreasing their effects. The binding of PLP to steroid
receptors for estrogen, progesterone, testosterone, and other steroid
hormones suggests that the vitamin B6 status of an individual may have
implications for diseases affected by steroid hormones, including
breast cancer and prostate cancers (4).

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. The effect
of vitamin B6 deficiency on the function of the immune system may be
partly related to the role of PLP in one-carbon metabolism (see
Disease Prevention).

Deficiency

Severe deficiency of vitamin B6 is uncommon. Alcoholics are thought to
be most at risk of vitamin B6 deficiency due to low dietary intakes
and impaired metabolism of the vitamin. In the early 1950s, seizures
were observed in infants as a result of severe vitamin B6 deficiency
caused by an error in the manufacture of infant formula. Abnormal
electroencephalogram (EEG) patterns have been noted in some studies of
vitamin B6 deficiency. Other neurologic symptoms noted in severe
vitamin B6 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 (2).

The Recommended Dietary Allowance (RDA)

Because vitamin B6 is involved in many aspects of metabolism, several
factors are likely to effect an individual's requirement for vitamin B6.
Of those factors, protein intake has been the most studied. Increased
dietary protein results in an increased requirement for vitamin B6,
probably because PLP is a coenzyme for many enzymes involved in amino
acid metabolism (6). Unlike previous recommendations, the Food and
Nutrition Board (FNB) of the Institute of Medicine did not express the
most recent RDA for vitamin B6 in terms of protein intake, although
the relationship was considered in setting the RDA (7). The current
RDA was revised by the Food and Nutrition Board (FNB) in 1998 and is
presented in the table below.

Recommended Dietary Allowance (RDA) for Vitamin B6

Life Stage 

Age 

Males (mg/day) 

Females (mg/day) 

Infants 

0-6 months

0.1 (AI)

0.1 (AI)

Infants 

7-12 months 

0.3 (AI) 

0.3 (AI) 

Children 

1-3 years 

0.5 

0.5 

Children

4-8 years 

0.6 

0.6 

Children 

9-13 years 

1.0 

1.0 

Adolescents 

14-18 years 

1.3 

1.2 

Adults 

19-50 years 

1.3 

1.3 

Adults 

51 years and older 

1.7 

1.5 

Pregnancy 

all ages 

1.9 

Breast-feeding 

all ages 

2.0

Disease Prevention

Homocysteine and cardiovascular disease

Even moderately elevated levels of homocysteine in the blood have been
associated with increased risk for cardiovascular disease, including
heart disease and stroke (8). During protein digestion, 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 converts
homocysteine back to methionine and is dependent on folic acid and
vitamin B12. The other pathway converts homocysteine to the amino acid
cysteine and requires two vitamin B6(PLP)-dependent enzymes. Thus, the
amount of homocysteine in the blood is regulated by at least three
vitamins: folic acid, vitamin B12, and vitamin B6 (diagram). Several
large observational studies have demonstrated an association between
low vitamin B6 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 B6 daily was only 67% of the
risk in women who consumed an average of 1.1 mg daily (9). Another
large prospective study found higher plasma levels of PLP were
associated with a decreased risk of cardiovascular disease independent
of homocysteine levels (10). Further, several studies have reported
that low plasma PLP status is a risk factor for coronary artery
disease (11-13). In contrast to folic acid supplementation, studies
supplementing individuals with only vitamin B6 have not resulted in
significant decreases in basal (fasting) levels of homocysteine.
However, one study found that vitamin B6 supplementation was effective
in lowering blood homocysteine levels after an oral dose of methionine
(methionine load test) was given (14), suggesting vitamin B6 may play
a role in the metabolism of homocysteine after meals.

Immune function

Low vitamin B6 intake and nutritional 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 reported in vitamin B6 deficient individuals
(15). Restoration of vitamin B6 status has resulted in normalization
of lymphocyte proliferation and interleukin-2 production, suggesting
that adequate vitamin B6 intake is important for optimal immune system
function in older individuals (15, 16). However, one study found that
the amount of vitamin B6 required to reverse these immune system
impairments in the elderly was 2.9 mg/day for men and 1.9 mg/day for
women; these vitamin B6 requirements are higher than the current RDA
(15).

Cognitive function

A few studies have associated cognitive decline in the elderly or
Alzheimer's disease with inadequate nutritional status of folic acid,
vitamin B12, and vitamin B6 and thus, elevated levels of homocysteine
(17). One observational study found that higher plasma vitamin B6
levels were associated with better performance on two measures of
memory, but plasma vitamin B6 levels were unrelated to performance on
18 other cognitive tests (18). Similarly, a double-blind, placebo-controlled
study in 38 healthy elderly men found that vitamin B6 supplementation
improved memory but had no effect on mood or mental performance (19).
Further, a placebo-controlled trial in 211 healthy younger,
middle-aged, and older women found that vitamin B6 supplementation (75
mg/day) for five weeks improved memory performance in some age groups
but had no effect on mood (20). Recently, a systematic review of
randomized trials concluded that there is inadequate evidence that
supplementation with vitamin B6, vitamin B12, or folic acid improves
cognition in those with normal or impaired cognitive function (21).
Because of mixed findings, it is presently unclear whether
supplementation with B vitamins might blunt cognitive decline in the
elderly. Further, it is not known if marginal B vitamin deficiencies,
which are relatively common in the elderly, even contribute to
age-associated declines in cognitive function, or whether both result
from processes associated with aging and/or disease.

Kidney stones

A large prospective study examined the relationship between vitamin B6
intake and the occurrence of symptomatic kidney stones in women. A
group of more than 85,000 women without a prior history of kidney
stones were followed over 14 years and those who consumed 40 mg or
more of vitamin B6 daily had only two thirds the risk of developing
kidney stones compared with those who consumed 3 mg or less (22).
However, in a group of more than 45,000 men followed over six years,
no association was found between vitamin B6 intake and the occurrence
of kidney stones (23). Limited data have shown that supplementation of
vitamin B6 at levels higher than the tolerable upper intake level (100
mg/day) decreases 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 B6 intake and the risk of
developing kidney stones requires further study before any
recommendations can be made.

Disease Treatment

Vitamin B6 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 that large supplemental doses of vitamin B6 are
beneficial (24).

Side effects of oral contraceptives

Because vitamin B6 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 B6 status. Abnormal tryptophan load tests in
women taking high-dose oral contraceptives in the 1960s and 1970s
suggested that these women were vitamin B6 deficient. Abnormal results
in the tryptophan load test led a number of clinicians to prescribe
high doses (100-150 mg/day) of vitamin B6 to women in order to relieve
depression and other side effects sometimes experienced with oral
contraceptives. However, most other indices of vitamin B6 status were
normal in women on high-dose oral contraceptives, and it is unlikely
that the abnormality in tryptophan metabolism was due to vitamin B6
deficiency (24). A more recent placebo-controlled study in women on
the lower dose oral contraceptives, which are commonly prescribed
today, found that doses up to 150 mg/day of vitamin B6 (pyridoxine)
had no benefit in preventing side effects, such as nausea, vomiting,
dizziness, depression, and irritability (25).

Premenstrual syndrome (PMS)

The use of vitamin B6 to relieve the side effects of high-dose oral
contraceptives led to the use of vitamin B6 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 12
placebo-controlled double-blind trials on vitamin B6 use for PMS
treatment concluded that evidence for a beneficial effect was weak
(26). A more recent review of 25 studies suggested that supplemental
vitamin B6, up to 100 mg/day, may be of value to treat PMS; however,
only limited conclusions could be drawn because most of the studies
were of poor quality (27).  

Depression

Because a key enzyme in the synthesis of the neurotransmitters
serotonin and norepinephrine is PLP-dependent, it has been suggested
that vitamin B6 deficiency may lead to depression.  However, clinical
trials have not provided convincing evidence that vitamin B6
supplementation is an effective treatment for depression (24, 28),
though vitamin B6 may have therapeutic efficacy in premenopausal women
(28).

Morning sickness (nausea and vomiting in pregnancy)

Vitamin B6 has been used since the 1940s to treat nausea during
pregnancy. Vitamin B6 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 B6 itself is considered safe during
pregnancy and has been used in pregnant women without any evidence of
fetal harm (29). The results of two double-blind, placebo-controlled
trials that used 25 mg of pyridoxine every eight hours for three days
(30) or 10 mg of pyridoxine every eight hours for five days (29)
suggest that vitamin B6 may be beneficial in alleviating morning
sickness. Each study found a slight but significant reduction in
nausea or vomiting in pregnant women. A recent systematic review of
placebo-controlled trials on nausea during early pregnancy found
vitamin B6 to be somewhat effective (31). 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 B6 status was low in individuals with carpal
tunnel syndrome and that supplementation with 100-200 mg/day over
several months was beneficial (32, 33). A recent study in men not
taking vitamin supplements found that decreased blood levels of PLP
were associated with increased pain, tingling, and nocturnal wakening,
all symptoms of carpal tunnel syndrome (34). Studies using
electrophysiological measurements of median nerve conduction have
largely failed to find an association between vitamin B6 deficiency
and carpal tunnel syndrome. While a few trials have noted some
symptomatic relief with vitamin B6 supplementation, double-blind,
placebo-controlled trials have not generally found vitamin B6 to be
effective in treating carpal tunnel syndrome (24, 35).

Sources

Food sources

Surveys in the U.S. have shown that dietary intake of vitamin B6
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 years old
consumed about 1.2 mg/day and 1.0 mg/day, respectively; both intakes
are lower than the current RDA. Certain plant foods contain a unique
form of vitamin B6 called pyridoxine glucoside; this form of vitamin B6
appears to be only about half as bioavailable as vitamin B6 from other
food sources or supplements. Vitamin B6 in a mixed diet has been found
to be approximately 75% bioavailable (7). In most cases, including
foods in the diet that are rich in vitamin B6 should supply enough to
prevent deficiency. However, those who follow a very restricted
vegetarian diet might need to increase their vitamin B6 intake by
eating foods fortified with vitamin B6 or by taking a supplement. Some
foods that are relatively rich in vitamin B6 and their vitamin B6
content in milligrams (mg) are listed in the table below.  For more
information on the nutrient content of specific foods, search the USDA
food composition database.

Food

Serving

Vitamin B6 (mg)

Fortified cereal

1. cup

0.5-2.5

Banana

1. medium

0.43

Salmon, wild, cooked

1. ounces

0.48

Turkey, without skin, cooked

1. ounces

0.39

Chicken, light meat without skin, cooked

1. ounces

0.51

Potato, Russet, baked, with skin

1. medium

0.70

Spinach, cooked

1. cup

0.44

Hazelnuts, dry roasted

1. ounce

0.18

Vegetable juice cocktail

1. ounces

0.26

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

Supplements

Vitamin B6 is available as pyridoxine hydrochloride in multivitamin,
vitamin B-complex, and vitamin B6 supplements (36).

Safety

Toxicity

Because adverse effects have only been documented from vitamin B6
supplements and never from food sources, safety concerning only the
supplemental form of vitamin B6 (pyridoxine) is discussed. Although
vitamin B6 is a water-soluble vitamin and is excreted in the urine,
long-term supplementation with very high doses of pyridoxine 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. Yet, none of the studies in which an objective neurological
examination was performed reported evidence of sensory nerve damage at
intakes below 200 mg pyridoxine daily (24). 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 (see table below) (7). 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.

Tolerable Upper Intake Level (UL) for Vitamin B6

Age Group  

UL (mg/day)

Infants 0-12 months

Not possible to establish

Children 1-3 years

30

Children 4-8 years  

40

Children 9-13 years  

60

Adolescents 14-18 years

80

Adults 19 years and older

100

Source of intake should be from food and formula only.

Drug interactions

Certain medications interfere with the metabolism of vitamin B6;
therefore, some individuals may be vulnerable to a vitamin B6
deficiency if supplemental vitamin B6 is not taken. Anti-tuberculosis
medications, including isoniazid and cycloserine, the metal chelator
penicillamine, and antiparkinsonian drugs including L-dopa, all form
complexes with vitamin B6 and thus create a functional deficiency.
Additionally, the efficacy of other medications may be altered by high
doses of vitamin B6. For instance, high doses of vitamin B6 have been
found to decrease the efficacy of two anticonvulsants, phenobarbital
and phenytoin, as well as L-dopa (4, 24).

Linus Pauling Institute Recommendation

Metabolic studies suggest that young women require 0.02 mg of vitamin
B6 per gram of protein consumed daily (6, 37, 38). Using the upper
boundary for acceptable levels of protein intake for women (100
grams/day), the daily vitamin B6 requirement for young women would be
calculated at 2.0 mg daily. Older adults may also require at least 2.0
mg/day. For these reasons, the Linus Pauling Institute recommends that
all adults consume at least 2.0 mg of vitamin B6 daily. Following the
Linus Pauling Institute recommendation to take a daily
multivitamin-mineral supplement containing 100% of the Daily Value for
vitamin B6 will ensure an intake of at least 2.0 mg/day of vitamin B6.
Although a vitamin B6 intake of 2.0 mg daily is slightly higher than
the most recent 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 B6
in older adults is approximately 2.0 mg daily (39); this requirement
could be even higher if the effect of marginally deficient vitamin B6
intakes on immune function and homocysteine levels are clarified.
Despite evidence that the requirement for vitamin B6 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 B6 daily.

References

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Written in February 2002 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in November 2007 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in November 2007 by:
Donald B. McCormick, Ph.D. 
Professor, Emeritus 
Department of Biochemistry 
Emory University School of Medicine 

Copyright 2000-2010  Linus Pauling Institute

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