New Leads in Developing Functional Markers for Vitamin B6 Status
Despite low awareness, over 10% of a well-nourished population such as the US has both low intakes and deficient or marginal vitamin status of vitamin B6. This is important because low vitamin B6 levels have been associated with increased risk of cardiovascular disease (see Cheng, Rimm). The current assessment of vitamin B6 status is currently assessed by measuring plasma pyridoxal 5’-phosphate (PLP) in blood. This measurement reflects nutrient intakes and reacts to supplementation, however there may be better ways to work out whether vitamin B6 status is adequate for health.
This is the question being answered by a recent publication from da Silva and colleagues. They pooled results from two studies done to produce marginal vitamin B6 status in healthy subjects (no mean feat, due to the ubiquity of vitamin B6 in the diet, see table on common dietary sources from the Office of Dietary Supplements). For 28 days, subjects consumed diets containing under 0.5mg vitamin B6, which is less than half the requirement for adults. The effect on vitamin B6 status, and other metabolites, was carefully measured. In particular, the effect of low intakes of vitamin B6 on one-carbon metabolism and tryptophan synthesis were measured.
The researchers found that sub-clinical vitamin B6 deficiency as measured by PLP levels could be induced by the protocol. There were some significant changes in amino acid concentrations that indicate that they are affected by intakes of vitamin B6. Creatine levels decreased and cystathione levels increased in the B6-deficient group. Creatine is manufactured in the body from amino acids arginine, glycine and methionine. The amino acid homocysteine can be converted to either methionine or cystathione, and it is possible that deficiency has affected the relative syntheisis rates of these amino acids. In addition, as both creatine and vitamin B6 are found in meat, and there was no control group in the study, creatine levels may have been decreased due to lower meat intake in the vitamin B6 restriction protocol. In tryptophan metabolism, tryptophan can be converted to niacin via vitamin B6. Before a meal, tryptophan concentrations were higher during vitamin B6 deficiency. Levels of kynurenic acid decreased and those of 3-hydroxykynurenine increased when subjects were deficiency. Kynurenic acid is a by-product of tryptophan metabolism, although higher levels are normally a sign of clinical deficiency and may be responsible for the confusion and seizures that are deficiency symptoms. High levels of 3-hydroxykynurenine however are linked with neuronal toxicity and oxidative stress.
The authors conclude that measuring cystathionine, 3-hydroxykynurenine, kynurenic acid, and creatine may be useful in assessing the functional effects of vitamin B6 status.
da Silva VR, Rios-Avila L, Lamers Y, Ralat MA, Midttun O, Quinlivan EP, Garrett TJ, Coats B, Shankar MN, Percival SS, Chi YY, Muller KE, Ueland PM, Stacpoole PW, Gregory JF 3rd. Metabolite Profile Analysis Reveals Functional Effects of 28-Day Vitamin B-6 Restriction on One-Carbon Metabolism and Tryptophan Catabolic Pathways in Healthy Men and Women. J Nutr. 2013 Aug 21. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/23966327
Cheng CH, Lin PT, Liaw YP, Ho CC, Tsai TP, Chou MC, Huang YC. Plasma pyridoxal 5'-phosphate and high-sensitivity C-reactive protein are independently associated with an increased risk of coronary artery disease. Nutrition. 2008 Mar;24(3):239-44. doi: 10.1016/j.nut.2007.12.003. http://www.ncbi.nlm.nih.gov/pubmed/18312786
Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, Hennekens C, Stampfer MJ. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA. 1998 Feb 4;279(5):359-64. http://www.ncbi.nlm.nih.gov/pubmed/9459468