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Simple Summary  In high-yield cows, most production diseases occur during transition periods. Alpha-tocopherol, the most biologically active form of vitamin E, declines in blood and reaches the lowest levels (hypovitaminosis E) around calving. Hypovitaminosis E is associated with the incidence of peripartum diseases. Therefore, many studies which have been published for more than 30 years have investigated the effects of α-tocopherol supplementation. This α-tocopherol deficiency was thought to be caused by complex factors. However, until recently, the physiological factors or pathways underlying hypovitaminosis E in the transition period have been poorly understood. In the last 10 years, the α-tocopherol-related genes expression, which regulate the metabolism, transportation, and tissue distribution of α-tocopherol in humans and rodents, has been reported in ruminant tissues. In this paper, we discuss at least six physiological phenomena that occur during the transition period and may be candidate factors predisposing to a decreased blood α-tocopherol level and hypovitaminosis E with changes in α-tocopherol-related genes expression.    Abstract  Levels of alpha-tocopherol (α-Toc) decline gradually in blood throughout prepartum, reaching lowest levels (hypovitaminosis E) around calving. Despite numerous reports about the disease risk in hypovitaminosis E and the effect of α-Toc supplementation on the health of transition dairy cows, its risk and supplemental effects are controversial. Here, we present some novel data about the disease risk of hypovitaminosis E and the effects of α-Toc supplementation in transition dairy cows. These data strongly demonstrate that hypovitaminosis E is a risk factor for the occurrence of peripartum disease. Furthermore, a study on the effectiveness of using serum vitamin levels as biomarkers to predict disease in dairy cows was reported, and a rapid field test for measuring vitamin levels was developed. By contrast, evidence for how hypovitaminosis E occurred during the transition period was scarce until the 2010s. Pioneering studies conducted with humans and rodents have identified and characterised some α-Toc-related proteins, molecular players involved in α-Toc regulation followed by a study in ruminants from the 2010s. Based on recent literature, the six physiological factors: (1) the decline in α-Toc intake from the close-up period; (2) changes in the digestive and absorptive functions of α-Toc; (3) the decline in plasma high-density lipoprotein as an α-Toc carrier; (4) increasing oxidative stress and consumption of α-Toc; (5) decreasing hepatic α-Toc transfer to circulation; and (6) increasing mammary α-Toc transfer from blood to colostrum, may be involved in α-Toc deficiency during the transition period. However, the mechanisms and pathways are poorly understood, and further studies are needed to understand the physiological role of α-Toc-related molecules in cattle. Understanding the molecular mechanisms underlying hypovitaminosis E will contribute to the prevention of peripartum disease and high performance in dairy cows.

The Physiological Roles of Vitamin E and Hypovitaminosis E in the Transition Period of High-Yielding Dairy Cows