Introduction to the Improvit project

Among the micronutrients B12 occupies a very special niche. It is naturally synthesized by the ruminal microflora. After intestinal absorption in the ileum, it is stored for use as co-enzymes in organs and muscles of the host or secreted in milk. Humans do not have a ruminal microflora, and are therefore totally dependent on B12 supplied through food intake. Since plant foods are devoid of B12, the human B12 status is correlated with intake of animal products. Worldwide there are 75 million vegetarians by choice and 1450 million by necessity. There is a high probability that a large fraction of these people are prone to B12 deficiency.

Vitamin B12 deficency has been associated with diverse disorders throughout the life span, from birth defects such as stunted growth, neural tube defects, anemia to hyperhomocysteinemia and neuro-cognitive disorders in adulthood. Also, low plasma B12 concentrations in pregnancy have been shown to be associated with diminished neuro-cognitive performance in offspring.

The dietary sources of the vitamin also seem to matter. Several dietary surveys in humans have shown that B12 status is highly correlated with dairy product intake, whereas the relationship with meat, poultry, eggs, fish and even synthetic B12 intake is weaker. Two hypotheses may explain the greater bioavailability of B12 naturally present in milk. One is related to the molecular form of the natural vitamin in milk (hydroxo-B12), which differs from the synthetic form used in supplements (cyano-B12). However, information on whole-body retention of the different forms of B12 in human subjects is scarce. Another explanation for the increased bioavailability of milk B12 may be related to the presence of specific components in milk facilitating its absorption. We have shown that in bovine milk, the predominant form of naturally occurring B12 is bound to transcobalamin, a protein that facilitates cellular uptake of B12 from systemic circulation.

The current recommended daily dairy intake in the western world holds about half of the recommended daily intake of B12. In the developing countries it is difficult to meet the recommended intake of dairy products or other sources of B12. This problem may be circumvented by development of a low-cost diary product with a high content of bioactive B12.

The main objective of IMPROVIT is to tailor and test a low-cost milk powder (cow or buffalo) enriched in bioavailable natural B12, suitable for human consumption and storage outside the cold-chain. The trials include the measurement of plasma B12, plasma amino acids, and vitamin B6 following intervention. Also, we wish to identify and compare the bioavailability of the endogenous B12 form in milk with equivalent amounts of the slightly different synthetic-B12 form used in supplements.

The study is an expansion of the ongoing TRIM project (, by the inclusion of low-meat eaters with reduced B12 status relative to omnivores.