Hazelnut Extract in Diarrheic Calves

Evidence

This consecutive, parallel, randomized clinical trial with longitudinal follow-up was conducted under CONSORT guidance at the University of Milan’s Clinic for Ruminants and Swine between March 2023 and June 2024. It enrolled hospitalized female Holstein calves with neonatal diarrhea that required intravenous infusion therapy. Eligibility required at least one marker of clinical illness: a demeanor score below 4, dehydration above 1, or base excess below −8 mmol/L; calves that had already received intravenous infusion therapy on the farm were excluded. The study population therefore represents a selected hospital cohort with illness serious enough to require medical intervention, not all calves with diarrhea. [pmid:42873768]

The trial enrolled 60 calves, with 30 assigned to standard care alone and 30 assigned to hazelnut skin extract plus the same standardized hospitalization and treatment protocol. Eligible calves were consecutively assigned through an a priori randomization list created with the Randomizer Android application. The extract was given orally with milk as an adjunct, while both groups received fluid therapy and antimicrobial administration within the clinic protocol. Investigators monitored clinical parameters, milk intake, body weight, hospitalization outcomes, sepsis scores, derivatives of reactive oxygen metabolites, and serum antioxidant capacity measured with the oxygen-adsorbent test. [pmid:42873768]

For longitudinal analyses, treatment group was modeled as a fixed effect and time was handled categorically, with the final follow-up time point used as the reference; results were expressed as incidence rate ratios or odds ratios with 95% confidence intervals. The reported comparison found no significant group difference in body weight, while body weight changed over time in both groups. The investigators also reported no significant between-group differences in clinical recovery, fecal score, hydration status, milk intake, weight gain, hospitalization duration, mortality, or the measured oxidative-stress markers. These are outcomes of the randomized adjunct comparison within a setting where all enrolled calves received comprehensive conventional treatment. [pmid:42873768]

Hospitalization duration did not differ significantly between the control group, with a median of 8 days and an interquartile range of 7–11 days, and the hazelnut skin extract group, with a median of 9 days and an interquartile range of 8–12 days (p = 0.294). Mortality at day 6 was also identical: 26 of 30 calves survived and 4 of 30 died in each group (p = 1.000). These specific results are compatible with no detected incremental difference in those measured outcomes under the tested regimen and hospital protocol; a non-significant comparison does not itself establish that the groups had identical underlying outcomes. [pmid:42873768]

The study question was narrow: whether oral hazelnut skin extract added to usual hospital management changed measured health or antioxidant outcomes in this selected cohort. It was not a comparison of hazelnut skin extract with no medical management, because fluid therapy and antimicrobial administration were components of care in both groups. Clinical improvement over follow-up was reported in both groups. Within that comparison, the authors reported no additional clinical or antioxidant benefit from short-term supplementation. The result should consequently be read as an adjunct-treatment finding in hospitalized diarrheic dairy calves rather than as a finding about prevention, oral-rehydration cases, or other calf populations. [pmid:42873768]

Analysis — Adjunct effect in hospitalized calves

The central pattern is a randomized, concurrently managed comparison in which the added extract did not separate from the control condition across the reported clinical, hospitalization, mortality, and oxidative-stress outcomes. Random allocation and standardized treatment protocols strengthen the internal comparison between the two groups that were enrolled. At the same time, the interpretation is bounded by what the trial tested: an adjunct administered alongside multiple elements of hospital care in calves selected for intravenous infusion therapy. Because both groups received that clinical management, changes over follow-up in either group do not isolate the contribution of the extract or of any single component of standard care. The reported absence of detected group differences is more informative for this defined hospitalized population and regimen than for calves with less severe disease or cases managed outside this clinic. The reported p-values describe compatibility of the observed group comparisons with the study’s statistical models; they do not by themselves establish clinical equivalence or quantify a clinically important difference that may remain unresolved. [pmid:42873768]

Limitations

Adequate blinding was not achieved because hazelnut skin extract caused a reddish discoloration of feces, creating a potential for observer bias in assessments that could be influenced by knowledge of group assignment. The extract was administered only as an adjunct within a comprehensive therapeutic protocol and only for a short duration. Selection of clinically ill calves requiring intravenous fluid administration limits direct extension of the findings to calves amenable to oral rehydration or to other care settings. The discussion also notes that defining neonatal calf diarrhea using fecal scoring alone can limit diagnostic precision, whereas behavior and hydration may be relevant to a more standardized assessment. These constraints qualify the measured comparison without changing the reported lack of detected additional benefit in the enrolled hospital cohort. [pmid:42873768]