Planta Med 2020; 86(18): 1375-1388
DOI: 10.1055/a-1260-3148
Biological and Pharmacological Activity
Original Papers

Effects of a Multicomponent Herbal Extract on the Course of Subclinical Ketosis in Dairy Cows – a Blinded Placebo-controlled Field-study

Manuela Durrer
1   Department of Clinical Research and Veterinary Public Health, Division of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Bern, Switzerland
2   Department of Livestock Science, Research Institute of Organic Agriculture (FiBL), Frick, Switzerland
Meike Mevissen
1   Department of Clinical Research and Veterinary Public Health, Division of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Bern, Switzerland
Mirjam Holinger
2   Department of Livestock Science, Research Institute of Organic Agriculture (FiBL), Frick, Switzerland
3   Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
Sandra Graf-Schiller
4   SaluVet GmbH, Bad Waldsee, Germany
Philipp Mayer
4   SaluVet GmbH, Bad Waldsee, Germany
3   Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
Rupert Bruckmaier
5   Department of Clinical Research and Veterinary Public Health, Division of Veterinary Physiology, Vetsuisse Faculty, University of Bern, Switzerland
Michael Walkenhorst
2   Department of Livestock Science, Research Institute of Organic Agriculture (FiBL), Frick, Switzerland
› Author Affiliations


A blinded placebo-controlled multi-center on-farm trial was conducted in dairy cows with subclinical ketosis to investigate effects of a multicomponent herbal extract. Blood ketone levels were measured weekly in early lactating cows from 16 Swiss herds. Cows were subclassified based on their initial blood-β-hydroxybutyrate levels (≥ 1.0 [KET-low, 84 cows] and > 1.2 mmol/L [KET-high, 39 cows]) and randomly distributed to 3 groups treated orally with herbal extract containing Camellia sinensis, Cichcorium intybus, Gentiana lutea, Glycyrrhiza glabra, Taraxacum officinale, Trigonella foenum-graecum, and Zingiber officinale, sodium propionate, or placebo twice a day for 5 days. Milk yield, milk acetone, blood-β-hydroxybutyrate, glucose, nonesterified fatty acids, gamma-glutamyl transferase, and glutamate dehydrogenase were analyzed over 2 wk. Linear mixed effect models were used for data analysis. No effects were found for nonesterifed fatty acids, gamma-glutamyl transferase, and glucose. Significantly higher glutamate dehydrogenase (29.71 U/L) values were found in herbal extract-treated animals compared to sodium propionate on day 7 (22.33 U/L). By trend, higher blood-β-hydroxybutyrate levels (1.36 mmol/L) were found in the placebo group of KET-high-cows on day 14 compared to the sodium propionate group (0.91 mmol/L). Milk yields of all treatment groups increased. Milking time and treatment showed a significant interaction for milk acetone: sodium propionate led to an immediate decrease, whereas herbal extracts resulted in a milk acetone decrease from day 7 on, reaching significantly lower milk acetone on day 14 (3.17 mg/L) when compared to placebo (4.89 mg/L). In conclusion, herbal extracts and sodium propionate are both likely to improve subclinical ketosis in dairy cows, however, by different modes of action.

Supporting Information

Publication History

Received: 31 January 2020

Accepted after revision: 04 September 2020

Article published online:
01 October 2020

© 2020. Thieme. All rights reserved.

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  • References

  • 1 Gross JJ, Bruckmaier RM. Invited review: metabolic challenges and adaptation during different functional stages of the mammary gland in dairy cows: perspectives for sustainable milk production. J Dairy Sci 2019; 102: 2828-2843
  • 2 Zarrin M, Grossen-Rosti L, Bruckmaier RM, Grose JJ. Elevation of blood beta-hydroxybutyrate concentration affects glucose metabolism in dairy cows before and after parturition. J Dairy Sci 2017; 100: 2323-2333
  • 3 Suthar VS, Canelas-Raposo J, Deniz A, Heuwieser W. Prevalence of subclinical ketosis and relationships with postpartum diseases in European dairy cows. J Dairy Sci 2013; 96: 2925-2938
  • 4 Brunner N, Groeger S, Raposo JC, Bruckmaier RM, Gross JJ. Prevalence of subclinical ketosis and production diseases in dairy cows in Central and South America, Africa, Asia, Australia, New Zealand, and Eastern Europe. Transl Anim Sci 2019; 3: 84-92
  • 5 Zakian A, Tehrani-Sharif M, Mokhber-Dezfouli MR, Nouri M, Constable PD. Evaluation of a point-of-care electrochemical meter to detect subclinical ketosis and hypoglycaemia in lactating dairy cows. Aust Vet J 2017; 95: 123-128
  • 6 Iwersen M, Klein-Jöbstl D, Pichler M, Roland L, Fidlschuster B, Schwendenwein I, Drillich M. Comparison of 2 electronic cowside tests to detect subclinical ketosis in dairy cows and the influence of the temperature and type of blood sample on the test results. J Dairy Sci 2013; 96: 1-12
  • 7 Caldeira MO, Dan D, Neuheuser AL, Sturmlin R, Weber C, Glauser DL, Stierli M, Schuler U, Moll J, Wegmann S, Bruckmaier RM, Gross JJ. Opportunities and limitations of milk mid-infrared spectra-based estimation of acetone and beta-hydroxybutyrate for the prediction of metabolic stress and ketosis in dairy cows. J Dairy Res 2020; 87: 196-203
  • 8 Denis-Robichaud J, Dubuc J, Lefebvre D, DesCoteaux L. Accuracy of milk ketone bodies from flow-injection analysis for the diagnosis of hyperketonemia in dairy cows. J Dairy Sci 2014; 97: 3364-3370
  • 9 Dorn K, Leiber F, Sundrum A, Holinger M, Mayer P, Walkenhorst M. A field trial on the effects of pure sodium propionate and a combination with herbal extracts on short term development of subclinical ketosis. Livest Sci 2016; 187: 87-95
  • 10 Santschi DE, Lacroix R, Durocher J, Duplessis M, Moore RK, Lefebvre DM. Prevalence of elevated milk beta-hydroxybutyrate concentrations in Holstein cows measured by Fourier-transform infrared analysis in Dairy Herd Improvement milk samples and association with milk yield and components. J Dairy Sci 2016; 99: 9263-9270
  • 11 McArt JAA, Nydam DV, Oetzel GR. A field trial on the effect of propylene glycol on displaced abomasum, removal from herd, and reproduction in fresh cows diagnosed with subclinical ketosis. J Dairy Sci 2012; 95: 2505-2512
  • 12 McArt JAA, Nydam DV, Ospina PA, Oetzel GR. A field trial on the effect of propylene glycol on milk yield and resolution of ketosis in fresh cows diagnosed with subclinical ketosis. J Dairy Sci 2011; 94: 6011-6020
  • 13 Tatone EH, Duffield TF, Capel MB, DeVries TJ, LeBlanc SJ, Gordon JL. A randomized controlled trial of dexamethasone as an adjunctive therapy to propylene glycol for treatment of hyperketonemia in postpartum dairy cattle. J Dairy Sci 2016; 99: 8991-9000
  • 14 Mann S, Leal Yepes FA, Wakshlag JJ, Behling-Kelly E, McArt JAA. The effect of different treatments for early-lactation hyperketonemia on liver triglycerides, glycogen, and expression of key metabolic enzymes in dairy cattle. J Dairy Sci 2018; 101: 1626-1637
  • 15 Mann S, Yepes FAL, Behling-Kelly E, McArt JAA. The effect of different treatments for early-lactation hyperketonemia on blood beta-hydroxybutyrate, plasma nonesterified fatty acids, glucose, insulin, and glucagon in dairy cattle. J Dairy Sci 2017; 100: 6470-6482
  • 16 Gordon JL, LeBlanc SJ, Kelton DF, Herdt TH, Neuder L, Duffield TF. Randomized clinical field trial on the effects of butaphosphan-cyanocobalamin and propylene glycol on ketosis resolution and milk production. J Dairy Sci 2017; 100: 3912-3921
  • 17 Gordon JL, Duffield TF, Herdt TH, Kelton DF, Neuder L, LeBlanc SJ. Effects of a combination butaphosphan and cyanocobalamin product and insulin on ketosis resolution and milk production. J Dairy Sci 2017; 100: 2954-2966
  • 18 Ruegsegger GJ, Schultz LH. Use of a combination of propylene glycol and niacin for subclinical ketosis. J Dairy Sci 1986; 69: 1411-1415
  • 19 Jeong JK, Choi IS, Moon SH, Lee SC, Kang HG, Jung YH, Park SB, Kim IH. Effect of 2 treatment protocols for ketosis on the resolution, postpartum health, milk yield, and reproductive outcomes of dairy cows. Theriogenology 2018; 106: 53-59
  • 20 Sahoo SS, Patra RC, Behera PC, Swarup D. Oxidative stress indices in the erythrocytes from lactating cows after treatment for subclinical ketosis with antioxidant incorporated in the therapeutic regime. Vet Res Commun 2009; 33: 281-290
  • 21 Green BL, McBride BW, Sandals D, Leslie KE, Bagg R, Dick P. The impact of a monensin controlled-release capsule on subclinical ketosis in the transition dairy cow. J Dairy Sci 1999; 82: 333-342
  • 22 Walkenhorst M, Leiber F, Maeschlie A, Kapp AN, Spengler-Neff A, Faleschini MT, Garo E, Hamburger M, Potterat O, Mayer P, Graf-Schiller S, Bieber A. A multicomponent herbal feed additive improves somatic cell counts in dairy cows – a two stage, multicentre, placebo-controlled long-term ond-farm trial. J Anim Physiol Anim Nutr 2020; DOI: 10.1111/jpn.13297.
  • 23 Villalba JJ, Provenza FD. Self-medication and homeostatic behaviour in herbivores: learning about the benefits of natureʼs pharmacy. Animal 2007; 1: 1360-1370
  • 24 Provenza FD, Kronberg SL, Gregorini P. Is grassfed meat and dairy better for human and environmental health?. Front Nutr 2019; 6: 26
  • 25 Villalba JJ, Costes-Thire M, Ginane C. Phytochemicals in animal health: diet selection and trade-offs between costs and benefits. Proc Nutr Soc 2017; 76: 113-121
  • 26 Stucki K, Cero MD, Vogl CR, Ivemeyer S, Meier B, Maeschli A, Hamburger M, Walkenhorst M. Ethnoveterinary contemporary knowledge of farmers in pre-alpine and alpine regions of the Swiss cantons of Bern and Lucerne compared to ancient and recent literature – Is there a tradition?. J Ethnopharmacol 2019; 234: 225-244
  • 27 Ayrle H, Mevissen M, Kaske M, Nathues H, Gruetzner N, Melzig M, Walkenhorst M. Medicinal plants–prophylactic and therapeutic options for gastrointestinal and respiratory diseases in calves and piglets? A systematic review. BMC Vet Res 2016; 12: 89
  • 28 Schutz K, Carle R, Schieber A. Taraxacum – a review on its phytochemical and pharmacological profile. J Ethnopharmacol 2006; 107: 313-323
  • 29 Mirzaee F, Hosseini A, Jouybari HB, Davoodi A, Azadbakht M. Medicinal, biological and phytochemical properties of Gentiana species. J Tradit Complement Med 2017; 7: 400-408
  • 30 Marx W, Kiss N, Isenring L. Is ginger beneficial for nausea and vomiting? An update of the literature. Curr Opin Support Palliat 2015; 9: 189-195
  • 31 Eu CH, Lim WY, Ton SH, bin Abdul Kadir K. Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet-induced obese rats. Lipids Health Dis 2010; 9: 81
  • 32 Davaatseren M, Hur HJ, Yang HJ, Hwang JT, Park JH, Kim HJ, Kim MJ, Kwon DY, Sung MJ. Taraxacum official (dandelion) leaf extract alleviates high-fat diet-induced nonalcoholic fatty liver. Food Chem Toxicol 2013; 58: 30-36
  • 33 Nagulapalli Venkata KC, Swaroop A, Bagchi D, Bishayee A. A small plant with big benefits: Fenugreek (Trigonella foenum-graecum Linn.) for disease prevention and health promotion. Mol Nutr Food Res 2017; 61: 6
  • 34 Carnuta MG, Deleanu M, Barbalata T, Toma L, Raileanu M, Sima AV, Stancu CS. Zingiber officinale extract administration diminishes steroyl-CoA desaturase gene expression and activity in hyperlipidemic hamster liver by reducing the oxidative and endoplasmic reticulum stress. Phytomedicine 2018; 48: 62-69
  • 35 Elgengaihi S, Mossa AT, Refaie AA, Aboubaker D. Hepatoprotective efficacy of Cichorium intybus L. extract against carbon tetrachloride-induced liver damage in rats. J Diet Suppl 2016; 13: 570-584
  • 36 Hong M, Li S, Tan HY, Wang N, Tsao SW, Feng Y. Current status of herbal medicines in chronic liver disease therapy: the biological effects, molecular targets and future prospects. Int J Mol Sci 2015; 16: 28705-28745
  • 37 Li JY, Cao HY, Liu P, Cheng GH, Sun MY. Glycyrrhizic acid in the treatment of liver diseases: literature review. Biomed Res Int 2014; 2014: 872139
  • 38 Gordon JL, Leblanc SJ, Duffield TF. Ketosis treatment in lactating dairy cattle. Vet Clin North Am Food Anim Pract 2013; 29: 433-445
  • 39 Andersson L, Emanuelson U. An epidemiological study of hyperketonaemia in Swedish dairy cows; determinants and the relation to fertility. Prev Vet Med 1985; 3: 449-462
  • 40 Berge AC, Vertenten G. A field study to determine the prevalence, dairy herd management systems, and fresh cow clinical conditions associated with ketosis in western European dairy herds. J Dairy Sci 2014; 97: 2145-2154
  • 41 Tatone EH, Duffield TF, LeBlanc SJ, DeVries TJ, Gordon JL. Investigating the within-herd prevalence and risk factors for ketosis in dairy cattle in Ontario as diagnosed by the test-day concentration of beta-hydroxybutyrate in milk. J Dairy Sci 2017; 100: 1308-1318
  • 42 Nuber U, van Dorland HA, Bruckmaier RM. Effects of butafosfan with or without cyanocobalamin on the metabolism of early lactating cows with subclinical ketosis. J Anim Physiol a Anim Nutr 2016; 100: 146-155
  • 43 Shridhar NB. Efficacy of Ketovet in treating bovine ketosis in cows. Indian J Anim Res 2009; 43: 197-199
  • 44 Enjalbert F, Nicot M, Bayourthe C, Moncoulon R. Ketone bodies in milk and blood of dairy cows: relationship between concentrations and utilization for detection of subclinical ketosis. J Dairy Sci 2001; 84: 583-589
  • 45 van der Drift SG, van Hulzen KJ, Teweldemedhn TG, Jorritsma R, Nielen M, Heuven HC. Genetic and nongenetic variation in plasma and milk beta-hydroxybutyrate and milk acetone concentrations of early-lactation dairy cows. J Dairy Sci 2012; 95: 6781-6787
  • 46 van Knegsel AT, van den Brand H, Dijkstra J, Tamminga S, Kemp B. Effect of dietary energy source on energy balance, production, metabolic disorders and reproduction in lactating dairy cattle. Reprod Nutr Dev 2005; 45: 665-688
  • 47 Cao Y, Zhang J, Yang W, Xia C, Zhang HY, Wang YH, Xu C. Predictive value of plasma parameters in the risk of postpartum ketosis in dairy cows. J Vet Res 2017; 61: 91-95
  • 48 Bruckmaier RM, Gross JJ. Lactational challenges in transition dairy cows. Anim Prod Sci 2017; 57: 1471-1481
  • 49 Song Y, Li X, Li Y, Li N, Shi X, Ding H, Zhang Y, Li X, Liu G, Wang Z. Non-esterified fatty acids activate the ROS-p38-p53/Nrf2 signaling pathway to induce bovine hepatocyte apoptosis in vitro. Apoptosis 2014; 19: 984-997
  • 50 Jinchun Z, Jie C. The effects of Taraxacum officinale extracts (TOE) supplementation on physical fatigue in mice. Afr J Tradit Complement Altern Med 2011; 8: 128-133
  • 51 Nwafor IC, Shale K, Achilonu MC. Chemical composition and nutritive benefits of chicory (Cichorium intybus) as an Ideal complementary and/or alternative livestock feed supplement. Sci World J 2017; 2017: 7343928
  • 52 Du X, Chen L, Huang D, Peng Z, Zhao C, Zhang Y, Zhu Y, Wang Z, Li X, Liu G. Elevated apoptosis in the liver of dairy cows with ketosis. Cell Physiol Biochem 2017; 43: 568-578
  • 53 Wirngo FE, Lambert MN, Jeppesen PB. The physiological effects of dandelion (Taraxacum Officinale) in Type 2 diabetes. Rev Diabet Stud 2016; 13: 113-131
  • 54 Al-Attar AM, Abu Zeid IM. Effect of tea (Camellia sinensis) and olive (Olea europaea L.) leaves extracts on male mice exposed to diazinon. BioMed Res Int 2013; 2013: 461415
  • 55 Saggu S, Sakeran MI, Zidan N, Tousson E, Mohan A, Rehman H. Ameliorating effect of chicory (Chichorium intybus L.) fruit extract against 4-tert-octylphenol induced liver injury and oxidative stress in male rats. Food Chem Toxiol 2014; 72: 138-146
  • 56 Belaid-Nouira Y, Bakhta H, Haouas Z, Flehi-Slim I, Neffati F, Najjar MF, Cheikh HB. Fenugreek seeds, a hepatoprotector forage crop against chronic AlCl3 toxicity. BMC Vet Res 2013; 9: 22
  • 57 Abdrabouh AE. Liver disorders related to exposure to gasoline fumes in male rats and role of fenugreek seed supplementation. Environ Sci Pollut Res Int 2019; 26: 8949-8957
  • 58 Yang R, Wang LQ, Yuan BC, Liu Y. The pharmacological activities of licorice. Planta Med 2015; 81: 1654-1669
  • 59 Saeed M, Abd El-Hack ME, Alagawany M, Arain MA, Arif M, Mirza MA, Naveed M, Chao S, Sarwar M, Sayab M, Dhama K. Chicory (Cichorium intybus) herb: chemical composition, pharmacology, nutritional and healthical applications. Int J Pharmacol 2017; 13: 351-360
  • 60 Alagawany M, Abd El-Hack ME, Saeed M, Naveed M, Arain MA, Arif M, Tiwari R, Khandia R, Khurana SK, Karthik K, Yatoo MI, Munjal A, Bhatt P, Sharun K, Iqbal HMN, Sun C, Dhama K. Nutritional applications and beneficial health applications of green tea and l-theanine in some animal species: a review. J Biomed Pharmacother 2017; 95: 1260-1275
  • 61 R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria. Accessed September 24, 2020 at:
  • 62 Bates D, Machler M, Bolker BM, Walker SC. Fitting linear mixed-effects models using lme4. J Stat Softw 2015; 67: 1-48
  • 63 Halekoh U, Hojsgaard S. Kenward-Roger approximation and parametric bootstrap methods for tests in linear mixed models – The R package pbkrtest. J Stat Softw 2014; 59: 1-32