The following answer is from a presentation made by Barry Bradford, animal science professor at Kansas State University. He presented the information last October at the Cornell Nutrition Conference.
Q: We are finding out more about oxidative stress and how it may contribute to metabolic inflammation in transition cows. The resulting inflammation may promote metabolic disorders. What are some of the nutritional opportunities to limit this problem?
A: Dietary antioxidants, notably vitamin E and selenium, are important for their ability to contribute to neutralization of reactive oxygen species (such as hydrogen peroxide), thereby impeding the progression toward inflammation.
Interestingly, plasma concentrations of α-tocopherol (vitamin E) decrease through the transition period (Weiss et al., 1990a), and low-antioxidant status is associated with transition cow disorders (LeBlanc et al., 2004; Mudron et al., 1997). Supplementing vitamin E prepartum improves antioxidant status (Weiss et al., 1990a).
Given the importance of antioxidants in modulating inflammation, it is not surprising that multiple studies have shown that supplementing vitamin E in excess of traditional recommendations decreases the incidence and severity of clinical mastitis (Smith et al.,1984; Weiss et al., 1990a). Recently, a meta-analysis showed that supplemental vitamin E is also effective at preventing retained placenta (Bourne et al., 2007).
Low plasma vitamin E concentrations are associated with increased incidence of fatty liver and displaced abomasum (Mudron et al., 1997). Surprisingly, no published studies have evaluated the effects of supplemental vitamin E on liver metabolism or incidence of metabolic disorders. Given that supplemental vitamin E can decrease inflammatory cytokine production (Poynter and Daynes, 1998) and improve liver antioxidant status in mice with fatty liver (Soltys et al., 2001), supplemental vitamin E may improve liver function in transition cows. Beta carotene, a precursor of vitamin A, can also function as an antioxidant (Spears and Weiss, 2008), and concentrations of both vitamin A and ß-carotene typically decrease during the transition period (LeBlanc et al., 2004).
Although much of the literature on antioxidants in transition cows demonstrates positive effects, these nutrients must be used with caution. In an effort to maximize the odds of observing a response, most studies are designed with rather dramatic treatments; for example, one classic study (Weiss et al., 1990b) compared vitamin E intakes of 574 IU/day (no supplemental vitamin E) to 1474 IU/day (supplementing 88 IU/pound dry matter). In many such scenarios, the control group is fed a diet that is marginally deficient in the nutrient of interest. On most dairies, this is not the case. As a result, adding large amounts vitamin E, for example, can sometimes push the supply of the nutrient high enough to cause mild toxicity. Supplementing 3000 IU/day vitamin E to transition cows with adequate vitamin E status resulted in pro-oxidant responses, increasing markers of lipid peroxidation and the incidence of mastitis (Bouwstra et al., 2010). Any treatment that alters oxidative balance should be evaluated carefully.
Finally, even non-nutritive antioxidants may serve to limit oxidative stress. In one recent study, supplementation of a feed antioxidant decreased peroxide and tended to increase total antioxidant capacity in plasma when fed to cows in early lactation (Wang et al., 2010). These responses were observed despite the presumed lack of absorption of these antioxidants, suggesting that simply limiting the absorption of unstable oxidized lipids from the diet can help to control oxidative stress. Such an approach would presumably also avoid the risk of toxicity inherent in feeding high amounts of lipidsoluble antioxidant vitamins.
Non-steroidal anti-inflammatory drugs (NSAIDs)
Because pathways other than oxidative stress can cause metabolic inflammation in transition cows, there may be merit to more directly combating inflammation to promote improved metabolic function. The NSAID class of drugs works in just this manner, by preventing the amplification of inflammatory mediators that leads to full-blown inflammation. In fact, several studies have already suggested that NSAIDs hold promise for improving transition cow health and productivity.
Cows treated with acetyl-salicylate (aspirin) for the first 5 days of lactation had significantly lower plasma concentrations of acute phase proteins and tended to have greater peak milk production than controls (Bertoni et al., 2004). In a similar study, aspirin treatment for 5 days postpartum improved milk yield in the first 2 months of lactation and increased first service conception rates (Trevisi and Bertoni, 2008). A relatively small number of cows was included in the study (23/treatment); however, ketosis incidence appeared to decrease with aspirin treatment (4.4 percent vs. 22.7 percent) while metritis incidence appeared to increase (30.4 percent vs. 13.6 percent). These results point to the tradeoffs between metabolic and immune function associated with decreased inflammation.
Our lab recently completed a study in which 78 transition cows were alternately provided with drinking water containing either 0 or 2.5 g/L sodium salicylate for the first 7 days postpartum (Farney and Bradford, unpublished). Consistent with our hypothesis, cows treated with sodium salicylate tended to produce 8 percent more energy-corrected milk over the first 3 weeks of lactation, with no overall difference in feed intake or incidence of metabolic or infectious diseases. However, the production response was driven primarily by an increase in milk fat content among the salicylate-treated cows, and metabolic profiling revealed that these cows had sustained elevations of plasma NEFA and ketone concentrations compared to control cows. Nevertheless, salicylate treatment still decreased liver triglyceride content at 3 weeks postpartum. These findings suggest still more complicated roles of inflammatory pathways; it may be that inflammation provides a “release valve” for the metabolic system, allowing the cow to slow the rate of lipolysis even as negative energy balance continues, albeit at the risk of impairing liver function.
We hope that continued investigation of the metabolic and signaling responses to this treatment will help to uncover the role that inflammation plays in regulating metabolism in early lactation.