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Impact of Lowering Dietary Cation-Anion Difference in Nonlactating Dairy Cows: A Meta-Analysis

E. Charbonneau^*,1, D. Pellerin^* and G. R. Oetzel

^* Département des Sciences Animales, Université Laval, QC, Canada G1K 7P4
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706

¹ Corresponding author: groetzel{at}wisc.edu

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS AND DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 
A meta-analysis of previous studies was performed to clarify the response of prepartum dairy cows to lowering dietary cation-anion difference (DCAD) and to compare different equations that have been proposed to calculate DCAD. Twenty-two published studies containing 75 treatment groups met criteria for inclusion in the meta-analysis. Five different equations used to calculate DCAD were compared for their association with clinical milk fever and urinary pH. The DCAD equation (Na + K) – (Cl + 0.6 S) was the most highly associated with clinical milk fever (R² = 0.44) and urinary pH (R² = 0.85). Lowering DCAD reduced clinical milk fever but also reduced DM intake. Lowered DCAD was associated with reduced urinary pH, blood bicarbonate, and blood CO₂, suggesting a metabolic acidosis with respiratory compensation. Blood pH was very slightly lowered by lowered DCAD. Lowering DCAD increased ionized Ca in blood before and at calving. The model predicted that lowering DCAD from +300 to 0 mEq/kg reduced risk for clinical milk fever from 16.4 to 3.2%, reduced urinary pH from about 8.1 to 7.0, and reduced DM intake by 11.3%.

Key Words: nonlactating dairy cow • dietary cation-anion difference • milk fever • urinary pH

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS AND DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 
Hypocalcemia is an important problem in dairy cattle around parturition. It occurs when cows are unable to compensate for the dramatic increase in Ca needed for colostrum production at calving. The most dramatic form of hypocalcemia is clinical milk fever, which can be fatal. Surviving cows have increased risk for retained fetal placenta, displaced abomasums, and mastitis (Curtis et al., 1983; Gröhn et al., 1989) and decreased milk yield (Block, 1984) compared with cows without clinical milk fever. Subclinical milk fever, a milder form of hypocalcemia, may also be detrimental and may put cows at higher risk for developing subsequent metabolic disorders (Huber et al., 1981; Oetzel et al., 1988).

Dishington (1975) first reported that feeding a mixture of chloride and sulfate salts before calving could dramatically reduce the incidence of clinical milk fever. Numerous studies that followed have confirmed that lowering DCAD before calving reduces the risk for clinical and subclinical milk fever. Lowered DCAD has been associated with a compensated metabolic acidosis, which is evidenced by reduced plasma bicarbonate (Goff and Horst, 1997; Joyce et al., 1997; Pehrson et al., 1999), lower urinary pH (Wang and Beede, 1992a; Eppard et al., 1996; Moore et al., 2000), and higher urinary net acid excretion (Wang and Beede, 1992b; Van Mosel et al., 1993; Vagnoni and Oetzel, 1998). Blood pH is compensated in part by bone accepting hydrogen ion in exchange for Ca (Lemann et al., 2003). Calcium excreted in the urine in response to acidosis may be retained when Ca demand increases. However, Schonewille et al. (1999) reported that the amount of Ca retained by the cow from urinary Ca loss was not sufficient to account for all of the extra Ca mobilized during an EDTA challenge. Other mechanisms are also apparently involved, such as increased tissue receptivity to parathyroid hormone during acidosis (Goff et al., 1991). Improved parathyroid hormone receptiveness results in increased production of active vitamin D, which in turn enhances bone resorption and intestinal absorption of Ca (Gaynor et al., 1989; Goff et al., 1991).

Numerous equations have been published for the calculation of DCAD in dairy cattle diets. The first published equation (Ender et al., 1971) was (Na + K) – (Cl + S). Other DCAD equations were proposed later to account for the contributions of dietary ions that are not completely bioavailable. These longer equations were (Na + K + 0.38 Ca + 0.30 Mg) – (Cl + 0.6 S + 0.5 P) (Horst and Goff, 1997), (Na + K + 0.15 Ca + 0.15 Mg) – (Cl + 0.2 S + 0.3 P) (Horst and Goff, 1997), and (Na + K + 0.15 Ca + 0.15 Mg) – (Cl + 0.6 S + 0.5 P) (National Research Council, 2001). A fifth equation, (Na + K) – (Cl + 0.6 S), was recently proposed by Goff et al. (2004). This equation appeared to be the most accurate in predicting blood pH and standard base excess from dietary mineral composition (Goff et al., 2004).

To date, different DCAD equations have only been evaluated within individual studies. Combining data from many published studies into a meta-analysis allows comparison of these equations across a variety of experimental conditions. A meta-analysis also provides additional statistical power that could detect significant differences in outcomes that are not statistically different in individual studies.

A meta-analysis of milk fever studies in dairy cows has been published (Oetzel, 1991). However, only a few of the studies included in that analysis reported dietary mineral composition determined by wet chemistry analysis, and many of the mineral values used to calculate DCAD from the studies included in this analysis were estimated from tables of feed ingredient composition. And since then, many additional studies evaluating the relationship between DCAD and numerous outcomes have been published. Statistical methods to perform meta-analysis have also improved (St-Pierre, 2001).

The objectives of this study were 1) to compare the different DCAD equations for their impact on clinical milk fever and urinary pH and 2) to evaluate the impact of lowering DCAD on clinical milk fever, urinary pH, DMI, measures of acid-base balance, and blood Ca concentrations.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS AND DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 
Study Selection
A meta-analysis on the effect of lowering DCAD in nonlactating dairy cows was conducted by pooling and analyzing data from previous studies. To be included in the meta-analysis, studies needed to meet all the following criteria: 1) peer-reviewed publication in print before 2004; 2) English or French language for at least the abstract of the publication; 3) nonlactating dairy cows used as the experimental animals; 4) dietary amounts of Na, K, Cl, and S reported; 5) use of wet chemistry procedures for dietary mineral analysis; 6) dietary analysis results within the range of reasonable expectations for dairy cattle diets; 7) outcomes that included clinical milk fever, urinary pH, DMI, measures of acid-base status, or blood Ca; and 8) no vitamin D treatments administered.

Twenty-two published studies for 75 different treatment groups met all the inclusion criteria (Table 1). Treatment groups excluded due to mineral analyses outside the range of reasonable expectations included the anionic treatment in Goff et al. (1991) and the 2 treatment groups in experiment 2 from Goff and Horst (1998) due to low reported Na content (0.04 and 0.03% Na, respectively, DM basis). Also excluded were all treatment groups in Oetzel et al. (1991) due to high reported S values in the basal diet (>0.47%, DM basis).

Because 3 equations included Ca, Mg, and P values in the calculation of DCAD, the reported dietary content of those minerals was recorded when available. Studies did not have to report values for those 3 minerals to be included in the analysis; however, they could not be included in the analysis for the DCAD equations that included these minerals. The valence of P was assumed to be 1.8, which represents the normal distribution of monohydrogen and dihydrogen forms of P in body tissues (Oetzel, 1993).

Data Recording from Selected Studies
Group mean values for clinical milk fever, urinary pH, DMI, blood pH, blood HCO₃^–, blood CO₂ partial pressure (pCO₂), and total or ionized blood Ca around calving were added to the analysis if they were reported for the study. Group means for DMI were recorded but only if cows were offered ad libitum feed intake. Many studies reported additional outcomes that could have been of interest; however, only the outcomes listed here were reported by a sufficient number of treatment groups to allow for valid statistical evaluation.

Data reported in differing units of measure were transformed to the same units. When a study did not report all possible outcomes, missing variables were considered as missing data. Studies with results reported for both primiparous and multiparous cows were split into separate treatment groups for those 2 categories.

Statistical Analyses
Effects of DCAD on Study Outcomes.
Mixed model procedures from SAS (SAS Institute, 1997) were used to evaluate the effect of lowering DCAD5 on study outcomes. The unit of measure was the mean value from treatment groups. Data were weighted by the number of cows in each study to help counteract variation between experiments (St-Pierre, 2001). The study was entered as a random effect. It was not possible to include slope and intercept by study as random effects, as suggested by St-Pierre (2001), because there were not enough different treatment groups in most of the studies.

Preliminary analyses were conducted to determine viability of linear models, and final models were then determined by logistic regression. Clinical milk fever data were transformed (arc sine square root) to meet homogeneity of variance criteria. Urinary pH data were also transformed (logit) to best represent the nonlinear relationship between DCAD and urinary pH.

Comparison of DCAD Equations.
The 5 different DCAD equations were analyzed for their relationship to clinical milk fever and urinary pH with the approach described above. Treatment groups for this analysis were limited to studies that reported data for all minerals (including Ca, Mg, and P) and for which all 5 equations could be calculated. For proper graphic representation of statistical results in 2 dimensions, the Y observation was adjusted to take into account the random effect of study. The coefficient of multiple regression (R²) calculations also used the adjusted Y observation (St-Pierre, 2001).

	RESULTS AND DISCUSSION

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Descriptive statistics of outcomes included in the analysis are presented in Table 2. All studies had to report dietary Na, K, Cl, and S to be included; therefore, DCAD1 and DCAD5 equations were available for all 75 treatment groups. Fifty-seven treatment groups were from studies also reporting Ca, Mg, and P values; DCAD2, DCAD3, and DCAD4 could be calculated for those treatment groups. Urinary pH results were reported for 48 treatment groups, and clinical milk fever was reported for 33 treatment groups. Maximum and minimum values are reported to demonstrate the wide range of independent and dependent variables represented in the studies.

View larger version (26K): [in this window] [in a new window]   Figure 1. Effect of dietary cation-anion difference (DCAD) on clinical milk fever. Five different DCAD equations are plotted: DCAD1 = (Na + K) – (Cl + S); DCAD2 = (Na + K + 0.38 Ca + 0.30 Mg) – (Cl + 0.60 S + 0.50 P); DCAD3 = (Na + K + 0.15 Ca + 0.15 Mg) – (Cl + 0.20 S + 0.30 P); DCAD4 = (Na + K + 0.15 Ca + 0.15 Mg) – (Cl + 0.60 S + 0.50 P); and DCAD5 = (Na + K) – (Cl + 0.6 S). Data are group treatment means from previous studies: = Eppard et al. (1996); • = Goff and Horst (1997); = Moore et al. (2000; primiparous); = Moore et al. (2000; multiparous); = Oetzel et al. (1988); = Roche et al. (2003); = Tucker et al. (1992; primiparous); = Tucker et al. (1992; multiparous).

All 5 DCAD equations were also significantly and negatively associated with urinary pH (Table 3). The R² values ranged from 0.58 to 0.78 (Table 3) with DCAD1 and DCAD5 having the highest correlation. Lowered DCAD resulted in a nonlinear decrease in urinary pH (Figure 2).

View larger version (28K): [in this window] [in a new window]   Figure 2. Effect of dietary cation-anion difference (DCAD) on urinary pH. Five different DCAD equations are plotted: DCAD1 = (Na + K) – (Cl + S); DCAD2 = (Na + K + 0.38 Ca + 0.30 Mg) – (Cl + 0.60 S + 0.50 P); DCAD3 = (Na + K + 0.15 Ca + 0.15 Mg) – (Cl + 0.20 S + 0.30 P); DCAD4 = (Na + K + 0.15 Ca + 0.15 Mg) – (Cl + 0.60 S + 0.50 P); and DCAD5 = (Na + K) – (Cl + 0.6 S). Data are group treatment means from previous studies: = Delaquis and Block (1995); • = Eppard et al. (1996); = Goff and Horst (1997); = Kume et al. (2001); = Moore et al. (2000; primiparous); = Moore et al. (2000; multiparous); = Pehrson et al. (1999); = Roche et al. (2003); * = Tucker et al. (1992; primiparous); + = Tucker et al. (1992; multiparous); x = Vagnoni and Oetzel (1998); = Van Mosel et al. (1993; primiparous); = Van Mosel et al. (1993; multiparous); Y = Wang and Beede (1990); Z = Wang and Beede (1992a); # = Wang and Beede (1992b).

Results from the urinary pH models suggest that urinary pH does not have to be decreased below about 7.0 to reasonably prevent clinical milk fever. For example, a DCAD5 of 0 mEq/kg would result in a group average urinary pH of 7.01 and a very low incidence of clinical milk fever (3.2%). The recommendation to reduce urinary pH to between 6.0 and 7.0 for milk fever prevention (Jardon, 1995) may be lower than necessary on the lower end of the range. For example, creating a urinary pH of 6.2 would require a very low DCAD5 of –150 mEq/kg and would reduce the modeled incidence of clinical milk fever to 0.4%. This could represent excessive acidification for only a modest benefit in milk fever prevention (about 2.8 percentage units) compared with reducing urinary pH only to about 7.0.

The longer DCAD equations, which incorporated other minerals besides Na, K, Cl, and S, showed no advantage over the shorter equations. And the best equation that included S (DCAD5) assigned it only 60% of the value of Na, K, or Cl. These findings support the theory that monovalent ions in the diet are the most bioavailable and therefore exert the strongest influence on acid-base balance (Goff et al., 2004).

The DCAD1 equation is widely used in applied dairy nutrition and is well correlated to urinary pH and clinical milk fever. However, the DCAD5 equation was equally correlated to clinical milk fever and had a much higher correlation to urinary pH. This result is in agreement with findings of a recent study (Goff et al., 2004), which was not included in the current study because it was published after the meta-analysis was completed.

Responses to DCAD
Because the DCAD5 equation had the highest correlations to clinical milk fever and urinary pH, this equation was chosen to evaluate the effect of DCAD on the other outcomes recorded. The magnitude of changes in outcomes was based on a reduction in DCAD5 from 300 to 0 mEq/kg.

Decreased DCAD5 in nonlactating cows significantly decreased DMI (Table 4 and Figure 3). The magnitude of reduction in DMI change with lowered DCAD was substantial, equaling a loss of 1.3 kg of DM/d (11.3%) for lowering DCAD5 by 300 mEq/kg. Most individual studies did not report significant reductions in DMI due to lowered DCAD; however, this meta-analysis of previous results clearly demonstrated a DMI reduction. Theories proposed to explain DMI reduction when DCAD is lowered include lack of palatability of the anion sources (Oetzel and Barmore, 1993) and some discomfort created by the acidosis itself (Vagnoni and Oetzel, 1998). However, neither of those theories has been specifically evaluated.

View larger version (11K): [in this window] [in a new window]   Figure 3. Effect of dietary cation-anion difference (DCAD5) [(Na + K)- (Cl + 0.6 S)] on DM intake in nonlactating cows. Data are group treatment means from previous studies: = Delaquis and Block (1995); • = Eppard et al. (1996); = Joyce et al. (1997); = Kume et al. (2001); = Leclerc and Block (1989); = Moore et al. (2000; primiparous); = Moore et al. (2000; multiparous); *diams; = Oetzel and Barmore (1993); * = Oetzel et al. (1988); + = Pehrson et al. (1999); x = Roche et al. (2003); * = Tucker et al. (1992; primiparous); + = Tucker et al. (1992; multiparous); Y = Vagnoni and Oetzel (1998).

Lowered DCAD resulted in a metabolic acidosis (significantly lowered adjusted blood HCO₃^– and lowered urinary pH) that was not fully compensated (significantly lowered blood pH). Decrease of DCAD5 by 300 mEq/kg changed blood HCO₃^– substantially (–2.2 mM or –8.6%; Table 4 and Figure 4). These results were expected and were previously reported as significant findings in individual studies. Blood pH has not been reported to be significantly affected by lowering DCAD in individual studies; however, the meta-analysis demonstrated a significant and negative effect of lowering DCAD5 on blood pH (Table 4). The reduction was biologically small (–0.018 pH units, or –0.25%) and resulted in blood pH values that remained within the expected normal range of about 7.35 to 7.45 (Constable, 1999). However, small changes in blood pH could have large effects on parathyroid hormone receptivity and ultimately on the risk for clinical milk fever (Goff et al., 1991).

View larger version (10K): [in this window] [in a new window]   Figure 4. Effect of dietary cation-anion difference (DCAD5) [(Na + K) – (Cl + 0.6 S)] on blood HCO3–. Data are group treatment means from previous studies: = Delaquis and Block (1995); • = Goff and Horst (1997); = Goff and Horst (1998); = Joyce et al. (1997); = Pehrson et al. (1999); = Tucker et al. (1992; primiparous); = Tucker et al. (1992; multiparous); *diams; = Vagnoni and Oetzel (1998); * = Wang and Beede (1990).

View larger version (9K): [in this window] [in a new window]   Figure 5. Effect of dietary cation-anion difference (DCAD5) [(Na + K) – (Cl + 0.6 S)] on blood partial pressure of CO2 (pCO2). Data are group treatment means from previous studies: = Delaquis and Block (1995); • = Gant et al. (1998); = Joyce et al. (1997); = Pehrson et al. (1999); = Tucker et al. (1992; primiparous); = Tucker et al. (1992; multiparous); = Vagnoni and Oetzel (1998).

View larger version (10K): [in this window] [in a new window]   Figure 6. Effect of dietary cation-anion difference (DCAD5) [(Na + K) – (Cl + 0.6 S)] on blood ionized Ca (iCa) in nonlactating dairy cows. Data are group treatment means from previous studies: = Gant et al. (1998); • = Joyce et al. (1997); = Moore et al. (2000; primiparous); = Moore et al. (2000; multiparous); = Vagnoni and Oetzel (1998); = Wang and Beede (1992a); = Wang and Beede (1992b).

View larger version (9K): [in this window] [in a new window]   Figure 7. Effect of dietary cation-anion difference (DCAD5) [(Na + K) – (Cl + 0.6 S)] on blood ionized Ca (iCa) in dairy cows after calving. Data are group treatment means from previous studies: = Joyce et al. (1997); • = Moore et al. (2000; primiparous); = Moore et al. (2000; multiparous); = Oetzel et al. (1988); = van Dijk and Lourens (2001; primiparous); = van Dijk and Lourens (2001; multiparous).

View larger version (11K): [in this window] [in a new window]   Figure 8. Effect of dietary cation-anion difference (DCAD5) [(Na + K) – (Cl + 0.6 S)] on blood total Ca in dairy cows after calving. Data are group treatment means from previous studies: = Leclerc and Block (1989); • = Oetzel et al. (1988); = Roche et al. (2002); = Roche et al. (2003); = Tucker et al. (1992; primiparous); = Tucker et al. (1992; multiparous); = van Dijk and Lourens (2001; primiparous); = van Dijk and Lourens (2001; multiparous).

	CONCLUSIONS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS AND DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 
Results from this meta-analysis confirm the effectiveness of lowering DCAD to decrease urinary pH and clinical milk fever. The DCAD5 equation [(Na + K) –(Cl + 0.6 S)] was the most highly correlated to clinical milk fever incidence and urinary pH. Lowering of DCAD in nonlactating cows resulted in a metabolic acidosis that was not fully compensated. Cows responded to acidosis via both metabolic and respiratory mechanisms. The meta-analysis confirmed that lowering of DCAD increases Ca available to prepartum dairy cows before and at calving and reduces the risk for clinical milk fever. Group mean urinary pH of about 7.0 appears to be a reasonable goal when feeding low DCAD diets. Acidification beyond urinary pH of about 7.0 could further decrease DMI without much additional benefit toward milk fever prevention.

	ACKNOWLEDGEMENTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS AND DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 
This study was supported by a grant from the Action concertée FQRNT-Novalait-MAPAQ and a scholarship from FQRNT. The authors gratefully acknowledge the statistical consultation provided by Murray Clayton (University of Wisconsin-Madison).

Received for publication August 15, 2005. Accepted for publication October 1, 2005.

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS AND DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 


Block, E. 1984. Manipulating dietary anions and cations for prepartum dairy cows to reduce incidence of milk fever. J. Dairy Sci. 67:2939–2948.[Abstract/Free Full Text]

Constable, P. D. 1999. Clinical assessment of acid-base status: Strong ion difference theory. Vet. Clin. North Am. Food Anim. Pract. 15:447–471.[Medline]

Curtis, C. R., H. N. Erb, C. J. Sniffen, R. D. Smith, P. A. Powers, M. C. Smith, M. E. White, R. B. Hillman, and E. J. Pearson. 1983. Association of parturient hypocalcemia with eight periparturient disorders in Holstein cows. J. Am. Vet. Med. Assoc. 183:559–561.[Medline]

Delaquis, A., and E. Block. 1995. Acid-base status, renal function, water, and macromineral metabolism of dry cows fed diets differing in cation-anion difference. J. Dairy Sci. 78:604–619.[Abstract]

Dishington, I. W. 1975. Prevention of milk fever (hypocalcemic paresis puerperalis) by dietary salt supplements. Acta Vet. Scand. 16:503–512.[Medline]

Ender, F., I. W. Dishington, and A. Helgebostad. 1971. Calcium balance studies in dairy cows under experimental induction and prevention of hypocalcaemic paresis puerperalis. Z. Tierphysiol. Tierernahr. Futtermittelkd. 28:233–256.[Medline]

Eppard, P. J., J. J. Veenhuizen, W. J. Cole, P. G. Comens-Keller, G. F. Hartnell, R. L. Hintz, L. Munyakazi, P. K. Olsson, R. H. Sorbet, T. C. White, C. A. Baile, R. J. Collier, J. P. Goff, and R. L. Horst. 1996. Effect of bovine somatotropin administered to periparturient dairy cows on the incidence of metabolic disease. J. Dairy Sci. 79:2170–2181.[Abstract]

Gant, R. G., W. Sanchez, and R. Kincaid. 1998. Effect of anionic salts on selenium metabolism in nonlactating, pregnant dairy cows. J. Dairy Sci. 81:1637–1642.[Abstract]

Gaynor, P. J., F. J. Mueller, J. K. Miller, N. Ramsey, J. P. Goff, and R. L. Horst. 1989. Parturient hypocalcemia in Jersey cows fed alfalfa haylage-based diets with different cation to anion ratios. J. Dairy Sci. 72:2525–2531.[Abstract/Free Full Text]

Goff, J. P., and R. L. Horst. 1997. Effects of the addition of potassium or sodium, but not calcium, to prepartum rations on milk fever in dairy cows. J. Dairy Sci. 80:176–186.[Abstract/Free Full Text]

Goff, J. P., and R. L. Horst. 1998. Use of hydrochloric acid as a source of anions for prevention of milk fever. J. Dairy Sci. 81:2874–2880.[Abstract]

Goff, J. P., R. L. Horst, F. J. Mueller, J. K. Miller, G. A. Kiess, and H. H. Dowlen. 1991. Addition of chloride to a prepartal diet high in cations increases 1,25-dihydroxyvitamin D response to hypocal-cemia preventing milk fever. J. Dairy Sci. 74:3863–3871.[Abstract]

Goff, J. P., R. Ruiz, and R. L. Horst. 2004. Relative acidifying activity of anionic salts commonly used to prevent milk fever. J. Dairy Sci. 87:1245–1255.[Abstract/Free Full Text]

Gröhn, Y. T., H. N. Erb, C. E. McCulloch, and H. S. Saloniemi. 1989. Epidemiology of metabolic disorders in dairy cattle: Association among host characteristics, disease, and production. J. Dairy Sci. 72:1876–1885.[Medline]

Horst, R. L., and J. P. Goff. 1997. Milk fever and dietary potassium. Pages 181–189 in Proc. Cornell Nutr. Conf. Feed Manuf., Rochester, NY. Cornell Univ., Ithaca, NY.

Huber, T. L., R. C. Wilson, A. J. Stattleman, and D. D. Goetsch. 1981. Effect of hypocalcemia on motility of the ruminant stomach. Am. J. Vet. Res. 42:1488–1490.[Medline]

Jardon, P. W. 1995. Using urine pH to monitor anionic salt programs. Compend. Contin. Educ. Pract. Vet. 17:860–862.

Joyce, P. W., W. K. Sanchez, and J. P. Goff. 1997. Effect of anionic salts in prepartum diets based on alfalfa. J. Dairy Sci. 80:2866–2875.[Abstract]

Kume, S., K. Toharmat, K. Nonaka, T. Oshiat, T. Nakui, and J. Ternouth. 2001. Relationship between crude protein and mineral concentrations in alfalfa and value of alfalfa silage as a mineral source for periparturient cows. Anim. Feed Sci. Technol. 93:157–168.

Leclerc, H., and E. Block. 1989. Effects of reducing dietary cation-anion balance for prepartum dairy cows with specific reference to hypocalcemic parturient paresis. Can. J. Anim. Sci. 69:411–423.

Lemann, J., D. A. Bushinsky, and L. L. Hamm. 2003. Bone buffering of acid and base in humans. Am. J. Physiol. Renal 285:F811–F832.[Abstract/Free Full Text]

Moore, S. J., M. J. Vandehaar, B. K. Sharma, T. E. Pilbeam, D. K. Beede, H. F. Bucholtz, J. S. Liesman, R. L. Horst, and J. P. Goff. 2000. Effects of altering dietary cation-anion difference on calcium and energy metabolism in peripartum cows. J. Dairy Sci. 83:2095–2104.[Abstract]

National Research Council. 2001. Page 192 in Nutrient Requirements of Dairy Cattle. 7th rev. ed. Natl. Acad. Sci., Washington, DC.

Oetzel, G. R. 1991. Meta-analysis of nutritional risk factors for milk fever in dairy cattle. J. Dairy Sci. 74:3900–3912.[Abstract]

Oetzel, G. R. 1993. Use of anionic salts for prevention of milk fever in dairy cattle. Compend. Contin. Educ. Pract. Vet. 15:1138–1146.

Oetzel, G. R. 1996. Effect of calcium chloride gel treatment in dairy cows on incidence of periparturient diseases. J. Am. Vet. Med. Assoc. 209:958–961.[Medline]

Oetzel, G. R., and J. A. Barmore. 1993. Intake of a concentrate mixture containing various anionic salts fed to pregnant, non-lactating dairy cows. J. Dairy Sci. 76:1617–1623.[Abstract]

Oetzel, G. R., M. J. Fettman, D. W. Hamar, and J. D. Olson. 1991. Screening of anionic salts for palatability, effects on acid-base status, and urinary calcium excretion in dairy cows. J. Dairy Sci. 74:965–971.[Abstract]

Oetzel, G. R., J. D. Olson, C. R. Curtis, and M. J. Fettman. 1988. Ammonium chloride and ammonium sulfate for prevention of parturient paresis in dairy cows. J. Dairy Sci. 71:3302–3309.[Abstract/Free Full Text]

Pehrson, B., C. Svensson, I. Gruvaeus, and M. Virkki. 1999. The influence of acidic diets on the acid-base balance of dry cows and the effect of fertilization on the mineral content of grass. J. Dairy Sci. 82:1310–1316.[Abstract]

Roche, J. R., D. Dalley, P. Moate, C. Grainger, M. Rath, and F. O’Mara. 2003. A low dietary cation-anion difference precalving and calcium supplementation postcalving increase plasma calcium but not milk production in a pasture-based system. J. Dairy Sci. 86:2658–2666.[Abstract/Free Full Text]

Roche, J. R., J. Morton, and S. Kolver. 2002. Sulfur and chloride play a non-acid-base status role in periparturient calcium homeostasis. J. Dairy Sci. 85:3444–3453.[Abstract/Free Full Text]

SAS Institute. 1997. SAS User’s Guide: Statistics. Version 6.03 ed. SAS Inst. Inc., Cary, NC.

Schonewille, J. T., A. T. van’t Klooster, H. Wouterse, and A. C. Beynen. 1999. Hypocalcemia induced by intravenous administration of disodium ethylenediaminotetraacetate and its effects on excretion of calcium in urine of cows fed a high chloride diet. J. Dairy Sci. 82:1317–1324.[Abstract]

St-Pierre, N. R. 2001. Integrating quantitative findings from multiple studies using mixed model methodology. J. Dairy Sci. 84:741–755.[Abstract]

Stewart, P. A. 1983. Modern quantitative acid-base chemistry. Can. J. Physiol. Pharmacol. 61:1444–1461.[Medline]

Tucker, W. B., J. F. Hogue, G. D. Adams, M. Aslam, I. S. Shin, and G. Morgan. 1992. Influence of dietary cation-anion balance during dry period on the occurrence of parturient paresis on cows fed excess calcium. J. Anim. Sci. 70:1238–1250.[Abstract]

Vagnoni, D. B., and G. R. Oetzel. 1998. Effects of dietary cation-anion difference on the acid-base status of dry cows. J. Dairy Sci. 81:1643–1652.[Abstract]

van Dijk, C., and D. Lourens. 2001. Effects of anionic salts in a prepartum dairy ration on calcium metabolism. J. So. Afr. Vet. Med. Assoc. 72:76–80.

Van Mosel, M., A. Th. Van’t Klooster, F. Van Mosel, and J. Van der Kuilen. 1993. Effects of reducing dietary [Na+ + K+) – (Cl– + SO4=)] on the rate of calcium mobilisation by dairy cows at parturition. Res. Vet. Sci. 54:1–9.[Medline]

Wang, C., and D. K. Beede. 1990. Effects of supplemental protein on acid-base status and calcium metabolism of nonlactating Jersey cows. J. Dairy Sci. 73:3178–3186.[Abstract]

Wang, C., and D. K. Beede. 1992a. Effects of ammonium chloride and sulfate on acid-base status and calcium metabolism of dry Jersey cows. J. Dairy Sci. 75:820–828.[Abstract]

Wang, C., and D. K. Beede. 1992b. Effects of diet magnesium on acid-base status and calcium metabolism of dry cows fed acidogenic salts. J. Dairy Sci. 75:829–836.[Abstract]

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