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Reducing the CP and MP content of diets allows to improve dairy cow nitrogen and MP efficiencies. However, when CP (≤13-14%) and MP (<95 g/kg DM of Protein Digestible in the Intestine, PDI) contents are reduced, DMI, milk yield and milk component secretion generally decrease. Improving the balance of nutrient supplies (such as starch or AA) could limit these decreases in milk secretions. These effects have been tested during short-term experiments. The aim of our study was to analyze the effects of increasing the bypass starch content or better balancing AA supplies through rumen-protected AA (RP-AA: Lys, Met, and His), on lactation persistency and milk component secretions when the treatments were applied to Holstein dairy cows from 56 to 183 DIM. Forty-four dairy cows were assigned randomly to 4 groups according to a factorial arrangement of the 4 treatments (LSHDAA-: Low Starch High Degradable in the rumen without any AA supplementation; LSHDAA+: LSHD with RP-AA supplementation; HSLDAA-: High Starch Low Degradable in the rumen without RP-AA supplementation, and HSLDAA+: HSLD with RP-AA supplementation). Increasing the bypass starch content led to increases in milk yield through lactose and milk protein yield with starch × time interactions: lactation persistency improved, as did all milk component secretions in HSLD vs. LSHD treatments. Increasing bypass starch slightly increased MP intake but decreased NEL intake. No changes in BCS and plasma insulin were observed when the bypass starch content was increased, probably because NEL content decreased. However, BW increased over time with a tendency to be higher with the higher bypass starch content. In addition, increasing bypass starch or RP-AA intakes increased Metabolic Energy (ME) efficiency (i.e., Milk Energy/ME). Increasing RP-AA supplies increased plasma Lys and Met concentrations, but the concentrations of plasma His only increased on LSHD. Milk protein yield as well as milk protein content and fat yield increased with RP-AA supplementation without any interaction with time. However, significant starch × AA × time interactions were observed for lactose and fat yields. These interactions mainly reflected lower lactation persistency and slopes of milk components in LSHDAA- than under the 3 other treatments. Interestingly, LSHDAA- corresponded to the lowest plasma His concentration compared with LSHDAA+, HSLDAA- and HSLDAA+. In multiparous cows (n = 32; 8 per dietary treatment), higher mammary cell proliferation, as measured by PCNA staining, was observed with both the HSLD vs. LSHD and the AA+ vs. AA- diets; however, only the 2 HSLD vs. LSHD diets gradually increased DMI and consequently whole nutrient supplies to sustain the higher milk persistency. Under a low MP content diet, the LSHDAA- diet proved to be a highly restrictive option for preserving lactation persistency; conversely, increasing the bypass starch content without increasing the NEL content appeared to be a promising solution to counter this negative effect on lactation persistency. Taking account of the type of nutrients (Starch or AA and specifically His) absorbed in dairy feeding systems seems important when reducing the MP supply.