Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits.

Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1ß, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.

Effects of rutin and buckwheat seeds on energy metabolism and methane production in dairy cows.

Flavonoids are secondary plant metabolites with several health promoting effects. As dairy cows often suffer from metabolic imbalance and health problems, interest is growing in health improvements by plant substances such as flavonoids. Our group has recently shown that the flavonoids quercetin and rutin (a glucorhamnoside of quercetin) are bioavailable in cows when given via a duodenal fistula or orally, respectively, affect glucose metabolism, and have beneficial effects on liver health. Furthermore, flavonoids may reduce rumen methane production in vitro through their antibacterial properties. To test the hypothesis that rutin has effects on energy metabolism, methane production, and production performance in dairy cows, we fed rutin trihydrate at a dose of 100mg/kg of body weight to a group of 7 lactating dairy cows for 2 wk in a crossover design. In a second experiment, 2 cows were fed the same ration but were supplemented with buckwheat seeds (Fagopyrum tartaricum), providing rutin at a dose comparable to the first experiment. Two other cows receiving barley supplements were used as controls in a change-over mode. Blood samples were taken weekly and respiration measurements were performed at the end of each treatment. Supplementation of pure rutin, but not of rutin contained in buckwheat seeds, increased the plasma quercetin content. Methane production and milk yield and composition were not affected by rutin treatment in either form. Plasma glucose, ß-hydroxybutyrate, and albumin were increased by pure rutin treatment, indicating a possible metabolic effect of rutin on energy metabolism of dairy cows. In addition, we did not show that in vivo ruminal methane production was reduced by rutin. In conclusion, we could not confirm earlier reports on in vitro methane reduction by rutin supplementation in dairy cows in established lactation.

The Effects of Oral Quercetin Supplementation on Splanchnic Glucose Metabolism in 1-Week-Old Calves Depend on Diet after Birth.

BACKGROUND: Inadequate colostrum supply results in insufficient intake of macronutrients and bioactive factors, thereby impairing gastrointestinal development and the maturation of glucose metabolism in neonatal calves. The flavonoid quercetin has been shown to have health-promoting properties, including effects in diabetic animals. However, quercetin interacts with intestinal glucose absorption and might therefore exert negative effects in neonates. OBJECTIVE: We evaluated the interaction between neonatal diet and quercetin feeding on splanchnic glucose metabolism in neonatal calves. METHODS: Calves (n = 28) were assigned to 4 groups and fed either colostrum or a milk-based formula on days 1 and 2 and supplemented daily with 148 µmol quercetin aglycone/kg body weight [colostrum with quercetin (CQ+)/formula with quercetin (FQ+)] or without this substance [colostrum without quercetin (CQ-)/formula with quercetin (FQ-)] from days 2-8. From day 3 onward, all calves received milk replacer. A xylose absorption test was performed on day 3, and on day 7, blood samples were collected to study glucose first-pass uptake after [(13)C6]-glucose feeding and intravenous [6,6-(2)H2]-glucose bolus injection. Plasma concentrations of metabolites and hormones were measured by taking additional blood samples. A biopsy specimen of the liver was harvested on day 8 to measure the mRNA expression of gluconeogenic enzymes. RESULTS: Higher postprandial plasma concentrations of glucose, lactate, urea, adrenaline, noradrenaline, insulin, and glucagon on day 7 in colostrum-fed calves indicate that metabolic processes were stimulated. Postabsorptive xylose and glucose plasma concentrations each increased by an additional 26%, and splanchnic glucose turnover decreased by 35% in colostrum-fed calves, suggesting improved glucose absorption and lower splanchnic glucose utilization in colostrum-fed calves. Quercetin supplementation resulted in higher noradrenaline concentrations and enhanced peak absorption and oxidation of [(13)C6]-glucose by 10%. Liver mitochondrial phosphoenolpyruvate carboxykinase mRNA abundance was reduced by 34% in colostrum-deprived calves. CONCLUSIONS: Feeding colostrum during the first 2 d of life is crucial for maturation of splanchnic glucose metabolism in calves. Supplementing quercetin improves gastrointestinal absorption capacity, particularly in colostrum-deprived calves.

Effects of a 6-wk intraduodenal supplementation with quercetin on energy metabolism and indicators of liver damage in periparturient dairy cows.

Periparturient dairy cows experience metabolic challenges that result in a negative energy balance (EB) and a range of postpartum health problems. To compensate for the negative EB, cows mobilize fatty acids from adipose tissues, which can lead to fatty liver disease, a periparturient metabolic disorder. Flavonoids, such as quercetin (Q), are polyphenolic substances found in all higher plants and have hepatoprotective potential and the ability to prevent or reduce lipid accumulation in the liver. In ruminants, few studies on the metabolic effects of Q are available, and thus this study was conducted to determine whether Q has beneficial effects on EB, lipid metabolism, and hepatoprotective effects in periparturient dairy cows. Quercetin was supplemented intraduodenally to circumvent Q degradation in the rumen. Cows (n=10) with duodenal fistulas were monitored for 7wk. Beginning 3wk before expected calving, 5 cows were treated with 100mg of quercetin dihydrate per kilogram of body weight daily in a 0.9% sodium chloride solution for a total period of 6wk, whereas the control cows received only the sodium chloride solution. The plasma flavonoid levels were higher in the Q-treated cows than in the control cows. A tendency for higher postpartum (pp) than antepartum (ap) plasma flavonoid levels was observed in the Q-treated cows than in the controls, which was potentially caused by a reduced capacity to metabolize Q. However, the metabolic status of the Q-treated cows did not differ from that of the control cows. The pp increases in plasma aspartate aminotransferase and glutamate dehydrogenase activities were less in the Q-treated cows than in the control cows. The Q had no effect on energy expenditures, but from ap to pp the cows had a slight decline in respiratory quotients. Irrespective of the treatment group, the oxidation of fat peaked after calving, suggesting that the increase occurred because of an increased supply of fatty acids from lipomobilization. In conclusion, supplementation with Q resulted in lower pp plasma aminotransferase and glutamate dehydrogenase, which indicated reduced liver damage. However, the direct effects of Q on the liver and the implications for animal performance remain to be investigated.