VERONA, ITALY. There is ample evidence that low plasma levels of pyridoxal-5'-phosphate (PLP), the active metabolite of vitamin B6 (pyridoxine), are associated with an elevated risk of systemic inflammation. Inflammation, in turn, is associated with a greater risk of coronary artery disease (CAD). Italian researchers recently proposed that PLP may directly affect CAD risk through several other mechanisms:

• PLP inhibits platelet aggregation by blocking ADP receptors;
• Low levels of PLP have been associated with high cholesterol levels as well as with high levels of fibrinogen and the inflammation marker C-reactive protein (CRP).

The researchers at the University of Verona School of Medicine recently concluded a clinical trial to determine the association between PLP levels and CAD risk. The trial involved 475 patients with documented CAD and 267 controls free from CAD. All participants had blood samples drawn for the determination of PLP, CRP (high sensitivity), homocysteine (total), fibrinogen, cholesterol and triglycerides. Levels of creatinine, folate and vitamin B12 were also determined.

The researchers found that the average (median) PLP concentration was 36.3 nmol/L and that 63% of the CAD patients had levels below the median as compared to only 50% of the controls. After adjusting for all major cardiovascular risk factors, they concluded that participants with a PLP level below 36.3 nmol/L had an 89% greater risk of CAD than did participants with higher levels. Low PLP levels were found to be particularly detrimental if combined with high CRP levels or a high LDL/HDL cholesterol ratio. Patients with a PLP level below 36.3 nmol/L and a CRP level above 4.18 mg/L had a 4.61 times higher risk of CAD than did patients with a PLP level above 36.3 nmol/L and a CRP level below 0.81 mg/L. Similarly, patients with a PLP level below 36.3 nmol/L and a LDL/HDL ratio above 3.23 had an 11 times greater risk of CAD than did patients with a PLP level above 36.3 nmol/L and a LDL/HDL ratio below 1.97.

The researchers suggest that their results indicate that low vitamin-B6 status as measured PLP level may be an important risk factor for coronary heart disease. They point out that low PLP levels have already been associated with an increased risk for stroke, venous thrombosis and heart attack.
Friso, S, et al. Low plasma vitamin B-6 concentrations and modulation of coronary artery disease risk. American Journal of Clinical Nutrition, Vol. 79, June 2004, pp. 992-98

Editor's comment: These findings add to the already impressive body of evidence attesting to the crucial importance of vitamin B6 in cardiovascular health. Other researchers have found that supplementing (orally) with 40 mg/day of vitamin B6 will increase PLP levels to about 230 nmol/L within 3 days of beginning supplementation. Adequate amounts of vitamin-B2 and magnesium are required in order to convert vitamin B6 to PLP.