The present review focuses on methyl donor metabolism and nutrition in the periparturient and lactating dairy cow. Methyl donors are involved in one-carbon metabolism, which includes the folate and Met cycles. These cycles work in unison to support lipid, nucleotide, and protein synthesis, as well as methylation reactions and the maintenance of redox status. A key feature of one-carbon metabolism is the multi-step conversion of tetrahydrofolate to 5-methyltetrahyrofolate. Homocysteine and 5-methyltetrahyrofolate are utilized by vitamin B12-dependent Met synthase to couple the folate and Met cycles and generate Met. Methionine may also be remethylated from choline-derived betaine under the action of betaine hydroxymethyltransferase. Regardless, Met is converted within the Met cycle to S-adenosylmethionine, which is universally utilized in methyl-group transfer reactions including the synthesis of phosphatidylcholine. Homocysteine may also enter the transsulfuration pathway to generate glutathione or taurine for scavenging of reactive oxygen metabolites. In the transition cow, a high demand exists for compounds with a labile methyl group. Limited methyl group supply may contribute to inadequate hepatic phosphatidylcholine synthesis and hepatic triglyceride export, systemic oxidative stress, and compromised milk production. To minimize the perils associated with methyl donor deficiency, the peripartum cow relies on de novo methylneogenesis from tetrahydrofolate. In addition, dietary supplementation of rumen-protected folic acid, vitamin B12, Met, choline, and betaine are potential nutritional approaches to target one-carbon pools and improve methyl donor balance in transition cows. Such strategies have merit considering research demonstrating their ability to improve milk production efficiency, milk protein synthesis, hepatic health, and immune response. This review aims to summarize the current understanding of folic acid, vitamin B12, Met, choline, and betaine utilization in the dairy cow. Methyl donor co-supplementation, fatty acid feeding strategies that may optimize methyl donor supplementation efficacy, and potential epigenetic mechanisms are also considered.

In this paper, we examined the microbiome of the bovine rumen, feces, and milk and attempted to understand how the bacterial communities at each site affected the production and movement of vitamin B ₁₂ around the animal’s body. It was determined that the composition of the bovine rumen microbiome correlates well with vitamin B ₁₂ concentration, indicating that the rumen microbiota may be a good target for manipulation to improve production of this important vitamin.

In Québec first calving occurs on average at 27 mo, whereas the target is 23 to 24.5 mo to maximize herd profitability. The aim of this study was to quantify current and future heifer growth using individual heifer random regressions and to generate indicators (such as heifer weight and height at 15 and 24 mo, average daily gain before and after 15 mo, age at which optimal weight for breeding is attained, i.e., 55% of mature weight, and reliability of the 15- and 24-mo weight predictions) that could be used as a practical on-farm tool. Dairy heifer weight estimated by heart girth circumference and height measured at the withers (from 0 to 27 mo) were obtained from the Valacta database (DHI agency, Ste-Anne-de-Bellevue, QC, Canada) from 1995 to 2012. Indicators were calculated based on the current situation of Holstein (HO), Ayrshire (AY), Jersey (JE), and Brown Swiss (BS) heifer growth in Québec. Heifers with less than 2 records were excluded from the analysis. Mature weights were determined by weight at calving of cows from third or greater lactation for a given breed and were 710 kg for HO, 625 kg for AY, 470 kg for JE, and 670 kg for BS. Estimated weights at 15 and 24 mo were 425 and 627, 334 and 482, 297 and 429, and 379 and 560 kg for HO, AY, JE, and BS, respectively, which are heavy enough for breeding and calving, except for AY. Relative reliabilities of the 15- and 24-mo weight predictions were on average 89 and 60%, respectively, based on measurements up to 15 mo. For HO, AY, JE, and BS, wither heights at 15 and 24 mo were 134 and 143, 125 and 134, 122 and 131, and 130 and 140 cm, respectively. Age at optimal breeding weight was 13.6, 15.5, 12.6, and 14.5 mo for HO, AY, JE, and BS, respectively. These data suggest that it is realistic to expect a first calving at 24 mo for HO, JE, and BS. A growth delay was observed for AY; average daily gain was 655 and 538 g/d before and after 15 mo, respectively. The average daily gain before and after 15 mo was 848 and 747 g/d for HO, 603 and 486 g/d for JE, and 775 and 662 g/d for BS, respectively. These indicators could be calculated for an individual heifer and on a herd-level basis and used on farm as a management tool for reducing age at first breeding and at first calving.

As vitamin B12 is only synthesized by bacteria, ruminant products, especially dairy products, are excellent sources of this vitamin. This study aims to identify if diet and cow characteristics could affect vitamin B12 concentration in milk of dairy cows. Information on 1484 first, 1093 second and 1763 third and greater parity Holstein cows in 100 herds was collected during three consecutive milkings. During the first morning milking, all dietary ingredients given to cows were sampled and quantities offered were recorded throughout the day. Nutrient composition of ingredients was obtained by wet chemistry to reconstitute nutrient composition of the ration. Milk samples were taken with in-line milk meters during the evening milking of the 1st day and the morning milking of the 2nd day and were analyzed for vitamin B12 concentration. Milk yields were recorded and milk components were separately analyzed for each milking. Daily vitamin B12 concentration in milk was obtained using morning and evening vitamin B12 concentrations weighted with respective milk yield, then divided by daily yield. To decrease the number of interdependent variables to include in the multivariable model, a principal component analysis was carried out. Daily milk concentration of vitamin B12 averaged 3809±80 pg/ml, 4178±79 pg/ml and 4399±77 pg/ml for first, second and third, and greater lactation cows. Out of 11 principal components, six were significantly related to daily milk concentration of vitamin B12 when entered in the multivariable model. Results suggested that vitamin B12 concentration in milk was positively related to percentage of fiber and negatively related to starch as well as energy of the diet. Negative relationships were noted between vitamin B12 concentration in milk and milk yield as well as milk lactose concentration and positive relationships were observed between vitamin B12 concentration in milk and milk fat as well as protein concentrations. The percentages of chopped mixed silage and commercial energy supplement in the diet as well as cow BW were positively related to vitamin B12 in milk and percentages of baled mixed silage, corn and commercial protein supplement in the ration were negatively related to vitamin B12 concentration in milk. The pseudo-R 2 of the model was low (52%) suggesting that diet and cow characteristics have moderate impact on vitamin B12 concentration in milk. Moreover, when entering solely the principal component related to milk production in the model, the pseudo-R 2 was 46%. In conclusion, it suggests that studied diet characteristics have a marginal impact on vitamin B12 concentration in milk variation.

Biotin (B₈), folates (B₉), and vitamin B₁₂ (B₁₂) are involved and interrelated in several metabolic reactions related to energy and protein metabolism. We hypothesized that a low supply of one of the latter vitamins during the transition period would impair metabolic status. The purpose of this study was to evaluate the effect of B₈ supplementation on the response of lactation performance and selected energy and protein metabolites and hormones to a combined supplementation of B₉ and B₁₂ given to periparturient dairy cows, from d -21 to 21 relative to calving. A total of 32 multiparous Holstein cows housed in tie stalls were randomly assigned, according to their previous 305-d milk yield, to 8 incomplete blocks of 4 treatments: (1) a 2-mL weekly i.m. injection of saline (0.9% NaCl; B₈-/B₉B₁₂-); (2) 20 mg/d of dietary B₈ (unprotected from ruminal degradation) and 2-mL weekly i.m. injection of 0.9% NaCl (B₈+/B₉B₁₂-); (3) 2.6 g/d of dietary B₉ (unprotected) and 2-mL weekly i.m. injection of 10 mg of B₁₂ (B₈-/B₉B₁₂+); and (4) 20 mg/d of dietary B₈, 2.6 g/d of dietary B₉, and weekly i.m. injection of 10 mg of B₁₂ (B₈+/B₉B₁₂+) in a 2 × 2 factorial arrangement. Milk yield and dry matter intake were obtained daily and milk components weekly. Blood samples were taken weekly from d -21 to calving and 3 times per week from calving to 21 d following parturition. Prepartum plasma concentrations of glucose, insulin, nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHB), and adiponectin were unaffected by treatments. Biotin, B₉, and B₁₂ supplements increased their respective concentrations in plasma and milk. Cows fed the B₈ supplement tended to have lower dry matter intake, but only cows in B₈+/B₉B₁₂- had greater plasma concentrations of NEFA compared with B₈-/B₉B₁₂-. Milk and total solid yields were greater by 13.5 and 13.9%, respectively, for B₈-/B₉B₁₂+ [45.5 (standard error, SE: 1.8) and 5.81 (0.22) kg/d, respectively] compared with B₈-/B₉B₁₂- [40.1 (1.9) and 5.10 (0.23) kg/d, respectively], but these effects were suppressed when combined with the B₈ supplement. Cows in the B₈-/B₉B₁₂+ group had decreased plasma insulin and tended to have increased NEFA concentrations, but postpartum plasma concentrations of glucose, BHB, leptin, and adiponectin were not affected. These cows also mobilized more body fat reserves, as suggested by a tendency to increased plasma NEFA and more milk total solids compared with B₈-/B₉B₁₂- cows. However, plasma concentrations of BHB and adiponectin were similar among treatments. This suggests that the B₉ and B₁₂ supplements enhanced efficiency of energy metabolism in early lactation cows. Folic acid and B₁₂ supplementation increased postpartum plasma Cys and homocysteine concentrations but did not affect plasma Met concentration, suggesting an upregulation of the transsulfuration pathway. In summary, our results showed that, under the current experimental conditions, increasing B₈ supply did not improve responses to the B₉ and B₁₂ supplementation.

The objective of this cross-sectional study was to assess the variability of plasma folate and vitamin B12 concentrations in lactating Holstein cows across the United States and Canada. We also evaluated the effect of diet composition and cow characteristics on folate and vitamin B12 plasma vitamin concentrations. A total of 22 and 24 US and Canadian dairy herds were enrolled, totaling 427 and 476 cows at 10 to 197 days in milk across all US and Canadian herds, respectively. Blood samples were taken to analyze plasma folate and vitamin B12 concentrations, and ingredients of the diet were collected to determine nutrient composition. To reduce the number of interdependent variables in the analysis of the association of diet composition with plasma vitamin concentrations, we conducted a principal component analysis. Plasma folate concentrations were lower for US cows [13.4 ng/mL, 95% confidence interval (CI): 12.7-14.2] than for Canadian cows (14.5 ng/mL, 95% CI: 13.7-15.2), and the opposite was observed for plasma vitamin B12 concentrations (US 206 pg/mL, 95% CI: 192-221; Canada 170 pg/mL, 95% CI: 159-181). The highest plasma concentrations of both vitamins were observed in the Northwest region of the United States (Oregon and Washington). Cows in California had the lowest plasma folate concentrations, and cows in Québec and New York State had the lowest plasma vitamin B12 concentrations. Plasma folate concentrations were higher for multiparous than for primiparous cows and plasma vitamin B12 concentrations progressively increased from parity 1 to 3 and higher. For both studied vitamins, plasma concentrations were lower at 0 to 55 than at 56 to 200 days in milk. Of 3 principal components, the one associated with dietary carbohydrates was significantly correlated with plasma folate and vitamin B12 concentrations. Indeed, plasma folate concentrations decreased with dietary fiber concentrations (i.e., neutral and acid detergent fibers and lignin) and increased with dietary nonfiber carbohydrate concentrations. We obtained the opposite results for plasma vitamin B12 concentrations. Both multivariable models explained 41% (pseudo-R2) of the variation in plasma folate and vitamin B12 concentrations. Information gathered in this study is the first step toward determining sources of variation in plasma folate and vitamin B12 concentrations, as well as the vitamin status of cows.