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Histidine – a limiting amino acid for lactating dairy cows?

Fabio Giallongo and Alexander N. Hristov for Progressive Dairyman Published on 05 May 2017

Methionine (Met) and lysine (Lys) are the two most studied essential amino acids (AAs) and have been shown to be limiting output of milk protein in dairy cows fed North American rations. Histidine (His) is another of the 10 nutritionally essential AAs that must be provided in sufficient amounts in the diet of lactating cows.

Unlike Met and Lys, His is not yet commercially available in a rumen-protected (RP) form.



The 1945 Nobel laureate in chemistry, Artturi Ilmari Virtanen, first suggested the importance of His in dairy cow nutrition. In a series of studies with lactating cows in the ’60s, Virtanen proposed that His from rumen microbial protein was likely limiting milk protein synthesis.

AA analyses of total protein of the cows’ rumen contents showed that His had the lowest concentration among all essential AAs. Virtanen also observed a decrease in blood hemoglobin and attributed it to His deficiency. Blood hemoglobin, which contains about 8 percent His, is an endogenous source of His.

His gained more attention in recent years after post-ruminal infusion studies conducted in northern Europe showed that His was the most limiting AA for milk and milk protein yields in dairy cows fed diets based on grass silage and a concentrate supplement containing barley/oats and beet/citrus pulp, with or without feather meal.

Research at Penn State University

More recently, research conducted at Pennsylvania State University pointed to His as a limiting AA for lactating cows fed reduced-protein diets based on typical North American feed ingredients (corn silage, alfalfa haylage, corn grain, and whole soybeans and canola meal as protein supplements).

In such conditions, similar to those observed in the above-mentioned European studies, the rumen microbial protein provides most of the AAs needed for milk protein synthesis, and His can become a limiting AA in high-producing dairy cows.


This is because data from dairy NRC (2001), as well as Penn State data, have clearly shown lower His concentration in rumen microbial protein (2 percent, crude protein [CP] basis) compared with Met (2.4 percent) or His concentration in milk protein (2.7 percent).

Forages commonly used in North American dairy diets also have a low His content (1.8 percent corn silage, 1.7 percent alfalfa haylage, 1.9 percent alfalfa hay), whereas most plant concentrate feeds have His concentration similar to that of milk protein (3.1 percent corn, 2.8 percent soybean and canola meal).

In the first Penn State experiment with 48 Holstein cows, feeding a reduced-protein diet (13.6 percent CP) decreased dry matter intake (DMI), plasma His concentrations, milk yield and milk protein yield, compared with a diet meeting the metabolizable protein requirements of the cows (15.7 percent CP).

To address these negative effects, we supplemented the reduced-protein diet with RP Lys and RP Met. This strategy improved milk protein yield and decreased the difference in DMI and milk yield compared to the protein-adequate diet. Supplementation of the reduced-protein diet with RP Lys, RP Met and an experimental RP His further increased DMI, milk yield and plasma His to levels close to those of the protein-adequate diet.

The goal of the second trial was to evaluate the effects of slow-release urea and RP Met and RP His supplementation of a reduced-protein diet (14.8 percent CP). In this experiment, the reduced-protein diet did not affect DMI and yields of milk and milk components.

However, cows fed the reduced-protein diet gained less bodyweight compared to those fed a protein-adequate diet (16.7 percent CP) and also those fed the reduced-protein diet supplemented with slow-release urea (15.8 percent CP) and RP Met or RP Met + RP His. When RP His was added in combination with RP Met and slow-release urea, cows increased their DMI and milk protein content and yield.


Consistent with the first study, this experiment suggested the addition of His to reduced-protein diets could have a positive effect on DMI in dairy cows.

In the same study, we collected muscle tissues from 45 cows to evaluate the effects of dietary treatments on gene expression analysis of key genes in the regulation of protein synthesis and catabolism in skeletal muscle.

We observed that cows receiving the reduced-protein diet had higher products of gene expression (key proteins and mRNA), which indicated a higher rate of protein turnover in the muscle tissue, consistent with the lower bodyweight gain observed in the main experiment.

Supplementation of RP His decreased the abundance of a key protein (P-mTOR) in the muscle tissue, which indicated that His was most likely used by the mammary gland for milk protein synthesis rather than for muscle protein synthesis. This result was also in line with the observed increase in milk protein content and yield with addition of RP His to the reduced-protein diet.

In another study, cows fed a reduced-protein diet (14.5 percent CP) had lower DMI, yields of milk and milk components (fat and protein), and plasma His compared to cows fed a protein-adequate diet (16.5 percent CP). Cows fed the reduced-protein diet also had lower blood hemoglobin; our calculations suggested that this endogenous reserve supplied about 0.4 gram per day of His during the experiment.

Supplementation of RP Lys to the reduced-protein diet increased milk protein content, whereas addition of RP Met did not affect performance of the cows. Supplementing the reduced-protein diet with RP His improved DMI (to the level of the protein-adequate diet), milk protein content and numerically increased milkfat and protein yields. It also prevented the decrease of plasma His and blood hemoglobin observed in cows fed the reduced-protein diet.

Supplementation of the reduced-protein diet with the combination of the 3 RP AAs (Lys, Met and His) further increased yields of milkfat and protein – close to levels observed in the protein-adequate diet. The data from this study confirmed previous findings that His stimulates DMI and the combination of the three RP AA (Lys, Met and His) could further improve milk component yields in dairy cows fed reduced-protein diets.

The objective of the last experiment was to investigate the effects of a His-deficient diet providing adequate protein (16.2 percent CP), Met and Lys on lactational performance and the endogenous His reserves (blood hemoglobin and muscle carnosine) of dairy cows. Cows fed the His-deficient diet had lower DMI, yields of milk, protein and energy-corrected milk compared with the His-adequate diet.

The His-deficient diet also decreased plasma His and blood hemoglobin (indicating a supply of 0.7 gram per day of His from this endogenous reserve) but not muscle carnosine. This observation suggested blood hemoglobin seems to play a greater role than muscle carnosine in the supply of His during periods of deficiency – but not to the extent to alleviate the negative effects of a His-deficient diet on lactational performance of cows.

At the end of the study, we examined whether supplementation of the His-deficient diet with RP His could alleviate those negative effects. We found RP His supplementation improved DMI, plasma His and energy-corrected milk yield compared to the His-deficient diet.

These findings confirmed results from the previous studies that low dietary His supply could impair DMI, yields of milk and milk protein, and blood hemoglobin in dairy cows.

Conclusions and practical implications

Decreasing the protein content of dairy rations (less than 15 percent CP) has been shown to reduce nitrogen and ammonia emissions from dairy operations by improving the efficiency of dietary protein utilization and decreasing urinary nitrogen excretion of dairy cows.

However, feeding reduced-protein diets also decreases the supply of the key AAs Met, Lys and His, which can lead to milk and milk protein production losses or lower bodyweight during critical periods of the lactation cycle. In particular, feeding diets low in His but providing adequate protein, Met and Lys has been shown to decrease DMI and lactational performance of dairy cows.

Our research at Penn State has shown balancing such diets with RP Met and RP Lys or feeds rich in Met, Lys and His, is a strategy to avoid potential negative effects on dairy cows’ productivity.  end mark

Alexander N. Hristov is a professor of dairy nutrition at Pennsylvania State University. Email Alexander N. Hristov

Fabio Giallongo is a Ph.D. graduate from Pennsylvania State University. Email Fabio Giallongo.