Although epidemiological studies have found that vitamin B supplementation can decrease homocysteine levels, they have not consistently shown a decreased risk of cardiovascular events in taking the vitamins. Food and Nutrition Board, Institute of Medicine. Xiao Q, Freedman ND, Ren J, Hollenbeck AR, Abnet CC, Park Y. Intakes of folate, methionine, vitamin B6, and vitamin B12 with risk of esophageal and gastric cancer in a large cohort study. 2008;87(5):1446-1454. Folsom AR, Nieto FJ, McGovern PG, et al. This result remained after adjusting for intakes of folate, multivitamins, and methionine (nutrients that may be protective against colorectal cancer). B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial. However, most systematic reviews and meta-analyses of B-vitamin intervention studies to date have indicated a lack of causality between the decrease of fasting homocysteine levels and the prevention of cardiovascular events (28, 33-35). Morris MS, Picciano MF, Jacques PF, Selhub J. High levels of circulating homocysteine are associated with an increased risk of cardiovascular disease. Meydani SN, Ribaya-Mercado JD, Russell RM, Sahyoun N, Morrow FD, Gershoff SN. Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations. J Nutr. In animal tissues, pyridoxine is converted into pyridoxal phosphate, an active coenzyme form of vitamin B 6 A deficiency of pyridoxine in the diet gives rise to dermatitis and convulsions. Thus, the amount of homocysteine in the blood may be influenced by nutritional status of at least three B vitamins, namely folate, vitamin B12, and vitamin B6. Originally written in 2000 by:  Oregon State University, Updated in November 2007 by:  2011;141(5):835-842. Vitamin B6 is a water-soluble vitamin so that unused amounts will exit the body through the urine. celecoxib and naproxen) may also impair vitamin B6 metabolism (91). Ann Nutr Metab. Carpal tunnel syndrome (CTS) causes numbness, pain, and weakness of the hand and fingers due to compression of the median nerve at the wrist. (PubMed), 28. I. Washington, D.C.: International Life Sciences Institute; 2006:269-277. Lin PT, Cheng CH, Liaw YP, Lee BJ, Lee TW, Huang YC. PLoS One. Neurology. (PubMed). Another meta-analysis of five nested case-control studies found higher versus lower serum PLP levels to be associated with a 29% lower risk of breast cancer in postmenopausal, but not premenopausal, women (62). (PubMed), 72. Vitamin B-6 can also be taken as a supplement, typically as an oral capsule, tablet or liquid.People who have kidney disease or conditions that prevent the small intestine from absorbing nutrients from foods (malabsorption syndromes) are more likely to be vitamin B-6 deficient. Urol Res. 2004;15(12):3225-3232. (PubMed), 82. Am J Cardiol. The vitamin B6 forms were extracted from the tissues by perchloric acid and separated by ion ex- change chromatography. Bosy-Westphal A, Holzapfel A, Czech N, Muller MJ. Present Knowldege in Nutrition. Create healthy, balanced meals using this visual guide as a blueprint. Homocysteine and atherosclerosis. PLP is also involved in neurotransmitter, myelin, hemoglobin synthesis, and gene expression. J Alzheimers Dis. Schnackerz KD, Benesch RE, Kwong S, Benesch R, Helmreich EJ. The results of two double-blind, placebo-controlled trials, including 401 pregnant women that used 25 mg of pyridoxine every eight hours for three days (75) or 10 mg of pyridoxine every eight hours for five days (76), suggested that vitamin B6 may be beneficial in reducing nausea. (PubMed), 77. 1991;53(5):1275-1280. Vitamin B6 is also involved in the critical functioning of cells. Low plasma vitamin B-6 concentrations and modulation of coronary artery disease risk. (PubMed), 58. Pyridoxine is involved in the metabolism of tryptophan, methionine, cysteine, glutamic and other amino acids. Institute of Medicine. Pawelec G, Goldeck D, Derhovanessian E. Inflammation, ageing and chronic disease. 3. 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. (PubMed), 49. 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 (Table 3) (14). 2010;68(4):503-510. 2010;92(2):330-335. The information should not be used in place of a consultation with a competent health care or nutrition professional. Potter K, Hankey GJ, Green DJ, Eikelboom J, Jamrozik K, Arnolda LF. A systematic review of both epidemiological and clinical studies looked at the relationship of dietary intake or blood levels of vitamin B6 and all cancers. B vitamins, homocysteine, and neurocognitive function in the elderly. Pyridoxine therapy, along with dietary protein restriction, is also used in the management of vitamin B6 responsive homocystinuria caused by the deficiency of the PLP-dependent enzyme, cystathionine β synthase (72). Ellis JM, Kishi T, Azuma J, Folkers K. Vitamin B6 deficiency in patients with a clinical syndrome including the carpal tunnel defect. 1991;78(1):33-36. Lamers Y, Coats B, Ralat M, Quinlivan EP, Stacpoole PW, Gregory JF, 3rd. 2014;29C:23-28. The active form of pyridoxine, pyridoxal 5-phosphate (PLP), serves as an enzyme cofactor in over 100 enzyme reactions in carbohydrate, lipid, and amino acid metabolism. 2012;104(20):1562-1575. Gerhard GT, Duell PB. JAMA. Vitamin B6 has been widely studied for its role in disease prevention. A coenzyme form of _____ PYRIDOXINE ____ is an essential enzyme cofactor in the reaction that converts the amino acid __ TRYPTOPHAN _____ to Niacin. Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis. Yet, additional research is needed to confirm that this interaction can enhance RIP140/NRIP1 repressive activity on steroid receptor-mediated gene expression. The de novo thymidylate (dTMP) biosynthesis pathway involves three enzymes: dihydrofolate reductase (DHFR), serine hydroxymethyltransferase (SHMT), and thymidylate synthase (TYMS) (Figure 3). Abnormal tryptophan load tests in women taking high-dose oral contraceptives (OCs) in the 1960s and 1970s suggested that these women were vitamin B6 deficient, which led to the prescription of high doses of vitamin B6 (100-150 mg/day) to women taking OCs. 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. 2011;104(1-2):48-60. However, the impact of this on normal oxygen delivery to tissues is not known (6, 8). The Enzyme commission has catalogued more than 140 PLP-dependent activities, corresponding to ~4% of all classified activities. A few rare inborn metabolic disorders, including pyridoxine-dependent epilepsy (PDE) and pyridoxamine 5'-phosphate oxidase (PNPO) deficiency, are the cause of early-onset epileptic encephalopathies that are found to be responsive to pharmacologic doses of vitamin B6. In a recent study conducted in nine healthy young volunteers, the rise of homocysteine during the postprandial period (after a meal) was found to be greater with marginal vitamin B6 deficiency (mean plasma PLP level of 19 nanomoles/liter) as compared to vitamin B6 sufficiency (mean PLP level of 49 nanomoles/liter) (27). In a prospective study of 3,503 free-living people aged 65 and older from the Chicago Health and Aging Project, total vitamin B6 intakes (but not dietary intakes alone) were inversely correlated with the incidence of depressive symptoms during a mean follow-up period of 7.2 years (59). Even moderately elevated levels of homocysteine in the blood have been associated with increased risk for cardiovascular disease (CVD), including cardiac insufficiency (heart failure), CAD, myocardial infarction, and cerebrovascular attack (stroke) (25). Oregon State University, Reviewed in June 2014 by:  Homocysteine is an intermediate in the metabolism of methionine. flashcards on Quizlet. The authors reported an increased rate of cystathionine synthesis with vitamin B6 restriction, suggesting that homocysteine catabolism in the transsulfuration may be maintained or enhanced in response to a marginal reduction in PLP availability. (PubMed), 63. This pathway is known to be activated during pro-inflammatory immune responses and plays a critical role in immune tolerance of the fetus during pregnancy (15). Assessment of vitamin B-6 status in young women consuming a controlled diet containing four levels of vitamin B-6 provides an estimated average requirement and recommended dietary allowance. Vitamin B6, vitamin C, and carpal tunnel syndrome. In a randomized, placebo-controlled trial conducted in 225 elderly patients hospitalized for acute illness, a six-month intervention with daily multivitamin/mineral supplements improved nutritional B-vitamin status and decreased the number and severity of depressive symptoms when compared to placebo (81). pyridoxine [pir″ĭ-dok´sēn] one of the forms of vitamin B6, used as the hydrochloride salt in the prophylaxis and treatment of vitamin B6 deficiency. Pyridoxamine lowers oxalate excretion and kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria. Effect of vitamin B6 on the side effects of a low-dose combined oral contraceptive. Sahakian V, Rouse D, Sipes S, Rose N, Niebyl J. Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind placebo-controlled study. Choose from 90 different sets of term:plp = coenzyme of pyridoxine (b6). Vitamin B6 is also called Pyridoxine. (PubMed), 20. There is evidence to suggest that adequate vitamin B6 intake is important for optimal immune system function, especially in older individuals (16, 17). Key reactions in this pathway are PLP-dependent; in particular, PLP is the cofactor for the enzyme kynureninase, which catalyzes the conversion of 3-hydroxykynurenine to 3-hydroxyanthranilic acid. Corvallis, Oregon 97331, phone: 541-737-5075 | fax: 541-737-5077 In conclusion, the present study indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. Experimental studies have uncovered a mechanism by which PLP may affect the activity of steroid receptors and decrease their effects on gene expression. The activated forms of pyridoxal and pyridoxamine are active coenzyme forms, and the Specifically, the risk of having serum CRP levels greater than 10 mg/L (corresponding to high inflammatory activity) was 57% higher in individuals with vitamin B6 intakes lower than 2 mg/day compared to those with intakes equal to and above 5 mg/day (41). There are … 2008;27(1):127-136. (PubMed), 93. Pyridoxine is a hydroxymethylpyridine with hydroxymethyl groups at positions 4 and 5, a hydroxy group at position 3 and a methyl group at position 2. 2001;45(6):255-258. Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials. (National Academies Press), 15. 2010;103(5):926-935. Wu W, Kang S, Zhang D. Association of vitamin B6, vitamin B12 and methionine with risk of breast cancer: a dose-response meta-analysis. Vitamin B6. Eur J Clin Nutr. Several enzymatic reactions in the tryptophan-kynurenine pathway are dependent on vitamin B6 coenzyme, pyridoxal 5'-phosphate (PLP) (see Figure 2 above) (see Tryptophan metabolism). However, mammalian cells can interconvert it. Am J Clin Nutr. 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) has been used as a functional assessment of vitamin B6 status. 3. 2009;120(8):649-655. 1991;121(7):1062-1074. B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. This amount is slightly above the RDA but still 50 times lower than the tolerable upper intake level (UL) set by the Food and Nutrition Board (see Safety). Koren G, Clark S, Hankins GD, et al. Vitamin B6 comprises six compounds - pyridoxal, pyridoxine, pyridoxamine and their respective 5' phosphates (see table below). 2011;123(16):1763-1770. However when total B6 intake from food and supplements was assessed, the protective effect weakened. There were no differences in cardiac events or cardiac deaths in the vitamin B6 groups compared with the placebo group. (PubMed), 69. (PubMed), 10. 2012;142(7):1280-1285. In the NHANES 2003-2004 analysis, significantly more current and past users of oral contraceptives (OCs) among menstruating women had low plasma PLP levels compared to women who have never used OCs, suggesting that the estrogen content of OCs may interfere with vitamin B6 metabolism (see Side effects of oral contraceptives) (88). 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. The analysis of data collected in the US NHANES 2003-2004 has indicated that vitamin B6 intakes from food only averaged about 1.9 mg/day (88). (PubMed), 60. 1998;97(5):437-443. 4th ed. Deficiencies in one or all of these B vitamins may affect both remethylation and transsulfuration processes and result in abnormally elevated homocysteine levels. Hartman J, Frishman WH. 2004;62(3):96-104. Longitudinal association of vitamin B-6, folate, and vitamin B-12 with depressive symptoms among older adults over time. Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study. 10th ed: Wiley-Blackwell; 2012:307-320. A Cochrane review looked at 14 randomized controlled trials that evaluated the cognitive effects on people who used B vitamin supplements for at least three months. 2004;58(3):481-487. Cochrane Database Syst Rev. The most common form in human tissue is the 5'-phosphate form of pyridoxal (PLP) most of which is found in muscle bound to phosphorylase. Stockler S, Plecko B, Gospe SM, Jr., et al. (PubMed), 42. Pyridoxal 5' phosphate (PLP) and pyridoxamine 5' phosphate (PMP) are the active coenzyme forms of vitamin B6 [1,2]. 2005;36(6):1330-1340. 2007;55(1):81-86. Ebbing M, Bønaa KH, Arnesen E, Ueland PM, Nordrehaug JE, Rasmussen K, Njølstad I, Nilsen DW, Refsum H, Tverdal A, Vollset SE. Lancet Neurol. Page JH, Ma J, Chiuve SE, et al. McParlin C, O’Donnell A, Robson SC, Beyer F, Moloney E, Bryant A, Bradley J, Muirhead CR, Nelson-Piercy C, Newbury-Birch D, Norman J. [9,10], A blinded randomized controlled trial of 77 pregnant women found that 40 mg of vitamin B6 taken twice daily reduced the severity of mild to moderate nausea compared with a placebo. 2. 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 (90). Finally, although high doses of vitamin B6 (pyridoxine) have demonstrated no benefit in preventing the risk of side effects from OCs (94), the use of vitamin B6 supplements may be warranted in current and past OC users. On the other hand, high serum homocysteine may possibly be a risk factor for cognitive decline in the elderly, although the matter remains under debate. Other neurotransmitters, including glycine, D-serine, glutamate, histamine, and γ-aminobutyric acid (GABA), are also synthesized in reactions catalyzed by PLP-dependent enzymes (7). Onset of depression in elderly persons after hip fracture: implications for prevention and early intervention of late-life depression. (PubMed), 73. (PubMed), 95. A recent systematic review of randomized controlled trials on NVP symptoms during early pregnancy found supplemental vitamin B6 to be somewhat effective (77). Plasma vitamin B6 and the risk of colorectal cancer and adenoma in women. Nutr Rev. A lack of adequate vitamin B6, along with vitamin B12 and folic acid, can increase homocysteine levels. Aufiero E, Stitik TP, Foye PM, Chen B. Pyridoxine hydrochloride treatment of carpal tunnel syndrome: a review. Can Fam Physician. Substantial proportions of the naturally occurring pyridoxine in fruits, vegetables, and grains exist in glycosylated forms that exhibit reduced bioavailability . Vitatops Trial Study Group. 2011;34(1):83-91. [Epub ahead of print]  (PubMed), 48. 9th ed. A meta-analysis of epidemiological studies did not find that B6 supplements reduced colorectal cancer risk. Intake of folate, vitamin B6 and vitamin B12 and the risk of CHD: the Japan Public Health Center-Based Prospective Study Cohort I. J Am Coll Nutr. (PubMed), 41. Other neurologic symptoms observed 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 (12). (PubMed), 18. (PubMed), 53. The vitamin in supplement form shows the most promise for the treatment of pregnancy-induced nausea, but such use should only occur under the supervision of a physician. Sakakeeny L, Roubenoff R, Obin M, et al. A growing body of evidence currently suggests that low vitamin B6 status may increase the risk of cardiovascular disease through mechanisms independent of homocysteine lowering (41-43). Evidence is needed to determine whether 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. (PubMed), 31. What is Pyridoxal 5’Phosphate Pyridoxal 5’-phosphate (P5P) is the active coenzyme form of Vitamin B6 which can be directly utilized by the body without conversion. Specific receptor sites for pyridoxal 5'-phosphate and pyridoxal 5'-deoxymethylenephosphonate at the α and β NH2-terminal regions of hemoglobin. 1999;10(5):417-428. Even higher amounts of vitamin B6 supplements are sometimes prescribed for medical reasons, but under the supervision of a physician as excess vitamin B6 can cause toxicity. 2005;67(1):53-60. 2013;1:CD006612. A recent meta-analysis of nine randomized controlled trials reported a 10% reduction in stroke events with supplemental B vitamins, with greater benefits for high-risk subjects (e.g., those with kidney disease) (32). Larsson SC, Orsini N, Wolk A. Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies. J Popul Ther Clin Pharmacol. Stroke. Bender DA. Moreover, total vitamin B6 intakes (from food and supplements) lower than 2 mg/day were associated with high proportions of low plasma PLP levels: 16% in men aged 13-54 years, 24% in menstruating women, and 26% in individuals aged 65 years and older. Several tryptophan derivatives have been found to induce the death (apoptosis) or block the proliferation of certain types of immune cells, such as lymphocytes (in particular T-helper 1). Zhang XH, Ma J, Smith-Warner SA, Lee JE, Giovannucci E. Vitamin B6 and colorectal cancer: current evidence and future directions. Lussana F, Zighetti ML, Bucciarelli P, Cugno M, Cattaneo M. Blood levels of homocysteine, folate, vitamin B6 and B12 in women using oral contraceptives compared to non-users. However, most other indices of vitamin B6 status were normal in women on high-dose OCs, and the estrogen content of OCs appeared to be more likely responsible for the abnormality in tryptophan metabolism (88). (PubMed), 70. 2010;140(1):103-110. Keniston RC, Nathan PA, Leklem JE, Lockwood RS. Huang T, Chen Y, Yang B, Yang J, Wahlqvist ML, Li D. Meta-analysis of B vitamin supplementation on plasma homocysteine, cardiovascular and all-cause mortality. 2013;71(4):239-244. Vitamin B6 is believed to play a role in colorectal cancer through its enzyme activity that may reduce oxidative stress and the spread of tumor cells. Thus, while dietary vitamin B6 restriction impairs NAD synthesis from tryptophan, adequate PLP levels help maintain NAD formation from tryptophan (10). Am J Obstet Gynecol. It was found that PLP could interact with RIP140/NRIP1, a repressor of nuclear receptors known for its role in reproductive biology (11). In most cases, including foods in the diet that are rich in vitamin B6 should supply enough to meet the current RDA. Handbook of Vitamins. These observations were confirmed in the study of another cohort (Framingham Offspring Study) in which vitamin B6 status was linked to an overall inflammatory score based on the levels of 13 inflammation markers (including CRP, fibrinogen, tumor necrosis factor-α, and interleukin-6) (42). Ellis J, Folkers K, Watanabe T, et al. Am J Obstet Gynecol. the processes of decarboxylation, transamination). In contrast, studies supplementing individuals with only vitamin B6 have usually failed to show an effect on fasting levels of homocysteine (29, 30). 2014;100(1):250-255. Pyridoxine is found in largest amounts in rice bran, beans, yeast, kidneys, liver, and muscles. Markers of immune activation and inflammation have been associated with hyperhomocysteinemia (homocysteine levels >15 micromoles/liter) in individuals with coronary artery disease (CAD) (44). Yet, the flux ratio between methionine cycle and transsulfuration pathway appeared to favor homocysteine clearance by remethylation rather than transsulfuration in six out of nine participants (27). Am J Clin Nutr. 2013;143(9):1509-1519. Moreover, more women supplemented with pyridoxine-doxylamine (48.9%) than placebo-treated (32.8%) asked to continue their treatment at the end of the 15-day trial. Moreover, the inverse correlation between PLP levels and inflammatory scores remained significant regardless of vitamin B6 intakes, questioning again the nature of this relationship. More recently, a prospective study that followed a Japanese cohort of over 40,000 middle-aged individuals for 11.5 years reported a 48% lower risk of myocardial infarction in those in the highest (mean, 1.6 mg/day) versus lowest quintile (mean, 1.3 mg/day) of vitamin B6 intakes in non-supplement users (19). Anti-tuberculosis medications (e.g., isoniazid and cycloserine), the metal chelator penicillamine, and anti-parkinsonian drugs like L-Dopa can all form complexes with vitamin B6 and limit its bioavailability, thus creating a functional deficiency. 13. In: Pagon RA, Adam MP, Ardinger HH, et al., eds. In a randomized, double-blind, placebo-controlled trial in 563 individuals who suffered from a recent stroke, daily supplementation of 2 mg of folic acid, 0.5 mg of vitamin B12, and 25 mg of vitamin B6 halved the risk of developing a major depressive episode during a mean follow-up period of 7.1 years (60). Thromb Res. Lee BJ, Huang MC, Chung LJ, et al. (PubMed). The systematic review of nine prospective studies found either inverse or positive associations between vitamin B6 intakes and colorectal cancer (CRC) risk (61). Plasma pyridoxal-5-phosphate is inversely associated with systemic markers of inflammation in a population of US adults. Galluzzi L, Vacchelli E, Michels J, et al. Oncogene. Severe deficiency of vitamin B6 is uncommon. (PubMed), 16. 2006;22(11-12):1146-1151. B6-responsive disorders: a model of vitamin dependency. PLP functions as a coenzyme of 5-aminolevulinic acid synthase, which is involved in the synthesis of heme, an iron-containing component of hemoglobin. (PubMed), 39. Coexistence of symptoms of depression and low vitamin B6 status (plasma PLP level ≤20 nanomoles/liter) has been reported in a few cross-sectional studies (57, 58). A vitamin B6 deficiency most often occurs when other B vitamins in the body are low, particularly vitamin B12 and folic acid. [12] For moderate to severe nausea, a combination of vitamin B6 and doxylamine (an antihistamine) taken preventively before symptoms started was more effective than taking it after the nausea started. Healthy individuals utilize two different pathways to regenerate methionine from homocysteine in the methionine remethylation cycle (Figure 5). There is limited evidence suggesting that supplemental vitamin B6 may have therapeutic efficacy in the management of depression. 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. Moreover, two PLP-dependent enzymes are required to convert homocysteine to the amino acid cysteine in homocysteine transsulfuration pathway: cystathionine β synthase and cystathionine γ lyase (Figure 5). Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Vitamin B12, Pantothenic Acid, Biotin, and Choline. RDA: The Recommended Dietary Allowance (RDA) for men ages 14-50 years is 1.3 mg daily; 51+ years, 1.7 mg. Vitamin B-6. Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Washington D.C.: National Academies Press; 1998:150-195. Marti-Carvajal AJ, Sola I, Lathyris D, Karakitsiou DE, Simancas-Racines D. Homocysteine-lowering interventions for preventing cardiovascular events. Contraception. Pyridoxine taken by mouth (oral) is available without a prescription. Ulvik A, Midttun O, Pedersen ER, Eussen SJ, Nygard O, Ueland PM. Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease. Linus Pauling Institute  2014;110(5):1328-1333. However, in a group of more than 45,000 men followed for 14 years, no association was found between vitamin B6 intake and the occurrence of kidney stones (67). Pyridoxal phosphate also is required in the production of niacin; thus, pyridoxine deficiency can produce a secondary deficiency of vitamin B 3 . Linus Pauling Institute  Two earlier studies conducted in subjects with coronary artery disease failed to observe any benefit of supplemental vitamin B6 (40 mg/day) on CRC risk and mortality (reviewed in 64). Deficiency in another B vitamin, niacin, is easily prevented by adequate dietary intakes. Inconsistent evidence regarding the link between vitamin B6 intakes and breast cancer was also recently reported in a meta-analysis (62). Jane Higdon, Ph.D.  2010;203(6):571 e571-577. 2009;16(3):e407-429. World J Gastroenterol. [11]. BMC Cardiovasc Disord. Song Y, Manson JE, Lee IM, et al. Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women. Whelan AM, Jurgens TM, Naylor H. Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review. Skip to content. Vitamin B6 was originally included in the medication Bendectin, which was prescribed for NVP treatment and later withdrawn from the market due to unproven concerns that it increased the risk for birth defects. The phosphate ester derivative pyridoxal 5'-phosphate (PLP) is the bioactive coenzyme form involved in over 4% of all enzymatic reactions (Figure 1) (1-3). Leklem JE. Paul L, Ueland PM, Selhub J. Mechanistic perspective on the relationship between pyridoxal 5'-phosphate and inflammation. 2007;262(2):244-253. Bleie O, Semb AG, Grundt H, et al. Vitamin B6. 1987;46(4):659-664. 2009;27(3):259-265. (PubMed), 45. The UL for ad… However, the use of separate B6 supplements (apart from the RDA amounts in typical multivitamin preparations) is inconclusive and not recommended. Vutyavanich T, Wongtra-ngan S, Ruangsri R. Pyridoxine for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled trial. Early metabolic studies have indicated that the requirement for vitamin B6 in older adults is approximately 2 mg daily (95). 1999;81(1):7-20  (PubMed), 91. 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. Evidence for increased catabolism of vitamin B-6 during systemic inflammation. The other reaction is catalyzed by betaine homocysteine methyltransferase, which uses betaine as a source of methyl groups for the formation of methionine from homocysteine. In a case-control study that included 267 patients with CAD and 475 healthy controls, plasma PLP concentrations were inversely correlated with the levels of two markers of systemic inflammation, C-reactive protein (CRP) and fibrinogen (46). (PubMed), 11. The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis. Yet, the B-vitamin intervention had no effect on either the incidence of newly diagnosed cognitive impairments or on measures of cognitive performance when compared to placebo (53). (PubMed), 87. Am J Clin Nutr. (PubMed), 84. Rimm EB, Willett WC, Hu FB, et al. Therefore the American Heart Association does not advocate for the use of B vitamin supplements for reducing cardiovascular disease risk. Mol Genet Metab. (PubMed). Res Commun Chem Pathol Pharmacol. 2006;29(2-3):317-326. In a nested case-control study based on the Nurses' Health Study cohort and including 144 cases of myocardial infarction (of which 21 were fatal), women in the highest quartile of blood PLP levels (≥70 nanomoles/liter) had a 79% lower risk of myocardial infarction compared to those in the lowest quartile (<27.9 nanomoles/liter) (24). Gariballa S, Forster S. Effects of dietary supplements on depressive symptoms in older patients: a randomised double-blind placebo-controlled trial. 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