- Pyridoxic acid
For Patients & Caregivers
How It Works
Obtaining vitamin B6 through diet may help to reduce the risk of certain cancers, but using B6 supplements does not prevent cancer or reduce chemotherapy side effects.
Vitamin B6 is necessary for many physiological processes in the human body. These include reactions of cellular respiration, the release of glucose stores, and amino acid metabolism. Getting B6 through diet along with other nutrients is associated with cancer-preventive effects, but it cannot reduce side effects from chemotherapy. Even though lab studies show that B6 can have protective effects, high levels can also be toxic and cause nerve damage. In addition, a large analysis of postmenopausal women found that combined high intakes of B6 and B12, were associated with an unexpected increased risk of hip fracture.
B6 is readily available in food and deficiencies are uncommon. If a deficiency is suspected, it is important to see a healthcare practitioner to ensure correct diagnosis and supplement dosage.
To prevent cancer
Various studies show that nutrients including B6 obtained through diet have cancer-preventive effects, but this does not mean these same effects occur with supplements. In addition, long-term use of B6 supplements may increase the risk of lung cancer in male smokers.
To treat chemotherapy skin reactions
Several randomized trials show that vitamin B6 therapy is ineffective in preventing hand and foot syndrome, a skin condition caused by certain chemotherapies.
To treat nerve pain
A randomized trial did not find that high-dose B6 was more effective than placebo. In addition, there have been case reports of nerve damage caused by taking high doses of B6 in supplemental form.
To treat diabetes
In a study using supplements including B6, the risk of developing type 2 diabetes was not reduced.
To manage heart disease and its risk factors
High intakes of B6 obtained from foods are associated with lower levels of homocysteine, a risk factor for heart disease. B6 intake from food is also associated with reduced risk of death from stroke, heart disease, and heart failure. B6 may reduce high blood pressure in animals, but few studies about this have been done in humans.
To treat alcoholism
Alcoholism can lead to deficiency in vitamin B6 and many other nutrients, so supplementation may help improve nutritional status. However, proper diagnosis and treatment are needed.
Do Not Take If
- If a B6 deficiency is suspected, it is important to have a healthcare professional identify the cause and prescribe a safe dose of B6 supplementation if necessary.
- Some drugs may increase the need for B6. These include isoniazide, penicillamine, and oral contraceptives. Your healthcare professional should determine if this is the case and supplementation is needed.
For Healthcare Professionals
Vitamin B6 or pyridoxine, as part of the water-soluble vitamin B-complex family, is actually a mixture of 6 inter-convertible pyridine vitamers, or related compounds: pyridoxine, pyridoxamine, pyridoxal, and their 5′-phosphorylated forms (1). Although plants and microorganisms can synthesize B6 on their own, humans must acquire it from dietary sources. Because vitamin B6 is abundant in meats, fish, poultry, shellfish, leafy green vegetables, legumes, fruits, and whole grains, deficiencies are rare. For example, patients taking the antituberculosis drug isoniazide need to take vitamin B6 to prevent drug-induced peripheral neuropathy. Patients may use supplemental B6 to treat symptoms related to heart disease, hypertension, peripheral neuropathies, carpal tunnel syndrome, and diabetes.
Preclinical studies show that systemic administration of certain B vitamins including B6 has neuroprotective, antihypertensive (2), antinociceptive (3), and antitumor effects (4). In humans, higher B6 intake may lower serum homocysteine concentrations (5), but did not reduce the risk of developing type 2 diabetes (6). High dietary intakes of folate and B6 have been associated with reduced risk of mortality from stroke, coronary heart disease, and heart failure (7).
Studies suggest dietary intake of vitamin B6 may reduce risk for colorectal (14) (15) (16) and pancreatic cancers (47), and lower intakes are associated with increased risk of some gastrointestinal cancers (17) (18). Dietary B6 may also reduce risk of ovarian cancer (48) and all cancers, although this may occur because of the many other micronutrients that are also ingested (49).
Getting B6 through supplements is not associated with the same positive effects on disease risk. Conclusions from the Women’s Health Study indicate that supplementation with B6, B12, and folate did not decrease breast cancer risk (19), nor did it have an effect on overall risk of invasive cancer or breast cancer (20) (21). Long-term supplementation was also associated with increased risk of lung cancer, especially in male smokers (46).
Although vitamin B6 has been used empirically to prevent or treat chemotherapy-associated hand-foot syndrome (HFS), several randomized trials did not find benefit (22) (23) (24) (25) (50) (51). Other limited data suggest that higher doses might be needed (26). In one study, it did reduce the need for capecitabine dose modifications and incidence of severe HFS, but did not positively impact chemotherapy effects (27).
High intakes of vitamin B6 can have toxic effects including sensory and motor neuropathies, and some case reports of neurotoxicity have not been reversible (29) (52). In addition, a secondary analysis among postmenopausal women in the Nurses’ Health Study found that combined high intakes of B6 and B12 were associated with an unexpected increased risk of hip fracture (53). Large quantities of vitamin B6 should also be avoided in women who are pregnant or of childbearing potential (13).
Mechanism of Action
Vitamin B6 is a coenzyme in the folate metabolism pathway. Its phosphorylated metabolites are involved in amino acid metabolism, the transsulfuration pathway of homocysteine to cysteine, and glycogen phosphorylase activity which mobilizes glucose from glycogen (32). It is a cofactor along with cystathionine b synthase and cystathionase to produce cysteine and glutathione from their precursor homocysteine (33). Pyridoxal phosphate (PLP) is the major coenzyme form, the most abundant in animal tissue, and the cofactor for over 100 enzymes used in amino acid metabolism, including aminotransferases, decarboxylases, racemases, and dehydrases. It also facilitates mobilization of glucose units from glycogen via glycogen phosphorylase (32). PLP is also the active antiemetic form of B6, of which pyridoxine and pyridoxal have been identified as prodrugs (45).
In animal models, an excess-pyridoxine diet actively influenced cell-mediated immunity via enhanced IFN-γ production and Th1-polarization (34). In several cancer cell lines, B6 contributed to increased p21 gene expression via p53 activation (4). Proposed mechanisms for an inverse relationship of B6 intake and serum PLP with cancer risk include: 1) its participation in one-carbon metabolism that is essential for DNA synthesis, repair, and methylation; 2) the high uracil and chromosome breaks caused by B6 deficiency which may interfere with these processes leading to aberrant gene expression, DNA instability, and eventual disease; and 3) possible cancer-suppression effects through reductions in cell proliferation, angiogenesis, oxidative stress, inflammation, and nitric oxide synthesis (16) (21).
At the same time, because PLP is the metabolically active form of B6, it is thought to be responsible for instances of vitamin B6 toxicity (29). High circulating pyridoxine levels may have direct toxic effects on peripheral sensory ganglia neurons in the lower blood–nerve barrier, whereas the blood–brain barrier protects neurons in those regions from higher levels (35). The negative impact of B6 upon levels of other B vitamins appears to be dose-dependent and occur with chronic exposure (29).
High concentrations of vitamin B6 may result in severe peripheral sensory neuropathies and ataxia. Toxicities have reversed following discontinuation in some instances (37), but some case reports of neurotoxicity have not been reversible (29) (52).
Irreversible sensory ataxia in octogenarians: Three elderly patients presented with lack of voluntary muscle coordination and polyneuropathy for 3–8 months. Pyridoxine 600 mg daily was consumed for 3–10 years in a B1-6-12-combination tablet. B6 blood levels were markedly elevated at 66–104x ULN. After 2 years of vitamin discontinuation, the patients showed no significant improvement in either neuropathy or gait, and no other likely cause for neuropathy in these patients could be identified (29).
Severe sensorimotor neuropathy: Due to excess B6 intake in a 75-year-old white man, accompanied by yellowish-brown skin pigmentation. Product discontinuation led to improvement 1 year later, when he no longer used a wheelchair and could walk without a cane. Skin color also resolved, but ataxic signs were still present (38).
Small fiber neuropathy: In a 41-year-old woman with 2 years of progressive burning pain, numbness, tingling, and weakness in a stocking-glove distribution who was found to have severe pyridoxine toxicity. The suspected culprit was high intakes of B6, both from a B-complex vitamin as well as an energy drink (52).
Altretamine: In a study of cancer patients, pyridoxine diminished its therapeutic effect (39).
Oral contraceptives: May moderately increase pyridoxine requirements (40).
Levodopa: Enhances levodopa metabolism in patients, thereby reducing its effects (41) (42).
Penicillamine: May increase the requirements for pyridoxine (32).