Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of regulation (EC) No 1924/2006. The Commission has agreed with EU Member States that a certain number of Article 13 health claims would be eligible for further assessment by EFSA in order to be able to take a final decision on whether or not to include these claims in the list of permitted health claims. This opinion addresses the scientific substantiation of a health claim in relation to vitamin K2 and contribution to the normal function of the heart and blood vessels. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims, references that EFSA has received from Member States or directly from stakeholders and the additional information provided by the competent Authority of the United Kingdom for further assessment of this claim.
The food constituent that is the subject of the health claim is vitamin K2. The Panel considers that vitamin K2 is sufficiently characterised.
The claimed effect, which is eligible for further assessment, is normal function of the heart and blood vessels. The proposed target population is the general population. The Panel considers that contribution to the normal function of the heart and blood vessels is a beneficial physiological effect.
In its earlier opinion the Panel considered three cross-sectional studies and one prospective cohort study which investigated the relationship between vitamin K intake and arterial calcification or the elastic properties of the arteries, which may interfere with normal vascular structure and function. In the framework of further assessment one prospective cohort study on the association between vitamin K2 intakes and the risk of coronary heart disease and three unpublished human intervention studies which investigated the effect of vitamin K2 on blood concentrations of a matrix Gla-protein (MGP) and two animal studies on the mechanisms by which vitamin K2 could exert the claimed effect were provided.
This evaluation is based on the scientific references provided in the present and the previous submissions which addressed the relationship between vitamin K2 intake and changes in vascular/heart function (e.g. coronary heart disease) or changes in vascular/heart structure leading to changes in vascular/heart function (e.g. arterial calcification). Scientific references on the mechanisms by which vitamin K2 could exert the claimed effect in the target population were also considered.
Two prospective cohort studies investigated the association between vitamin K2 intakes and incidence of coronary heart disease and the degree of aortic calcification. The Panel notes that the results of the two prospective cohort studies are in conflict regarding the risk of coronary heart disease associated to vitamin K2 intakes, and that high intakes of vitamin K2 were associated with a significantly lower degree of aortic calcification after adjustment for confounders in one prospective cohort study.
Two cross-sectional studies investigated the relationship between vitamin K intake and arterial calcification. The Panel notes that one cross-sectional study reported that vitamin K2 intake was inversely related to the presence of coronary calcification while the other showed no association between vitamin K2 intake and breast arterial calcification, after adjustment for confounders.
The proposed mechanism by which vitamin K2 could exert the claimed effect is by contributing to the vitamin K-dependent activation (carboxylation) of MGP, a matrix Gla-protein which has been identified in vascular tissue. Increased levels of carboxylated MGP would reduce vascular calcification and decrease the risk of vascular (including coronary) events.
There is some evidence for a role of MGP in preventing calcification of soft tissues. In an MGP knock-out mouse model, spontaneous calcification of soft tissues (mostly arteries) occurred. Also in the Keutel syndrome, which results from a mutation of the gene encoding the human MGP, patients display several of the same features as the knockout mice, including abnormal calcification of ear and nose cartilage, and of the respiratory tract. However, whether changes in vitamin K2 intakes may induce changes in MGP carboxylation, which in turn could affect vascular function (e.g. calcification) or the risk of vascular events, has not been established.
In weighing the evidence, the Panel took into account the absence of human intervention studies from which conclusions could be drawn for the scientific substantiation of the claim, the inconsistency of the results reported in two cross-sectional studies regarding arterial calcification in women, that the results of two prospective cohort studies are in conflict regarding the risk of coronary heart disease associated with vitamin K2 intakes, that high intakes of vitamin K2 were associated with a significantly lower degree of aortic calcification in one prospective cohort study after adjustment for confounders, and that the evidence provided for a proposed mechanism is weak.
On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the dietary intake of vitamin K2 and contribution to the normal function of the heart and blood vessels.