The Science of Whole Food Diets in Dogs: Immune Function, Cytokines, and What a Clinical Trial Found
A prospective, randomized, open-labeled, crossover clinical trial published in Frontiers in Veterinary Science compared the immunological effects of a whole food diet versus an extruded dry diet in 16 healthy dogs over 134 days.
PUBLISHED IN FRONTEIRS IN VETERINARY SCIENCE
HEALTHY CLIENT-OWNED DOGS
MIDWESTERN UNIVERSITY COLLEGE OF VETERINARY MEDICINE
RANDOMIZED CLINICAL TRIAL
THE RESEARCH
A clinical trial examined what whole food diets do to immune markers in dogs at the cellular level.
In 2022, researchers at Midwestern University College of Veterinary Medicine designed a prospective, randomized, open-labeled, crossover clinical trial to examine the effect of a whole food diet on immune function and inflammatory phenotype in healthy dogs. The study was motivated by established evidence in human nutrition — where whole food diets have been associated with decreased inflammation and improved immune function — and the researchers sought to explore whether similar patterns might be observed in dogs.
The study enrolled 16 healthy, client-owned dogs. Each dog was fed either the whole food diet or an extruded dry diet for 67 days, then crossed over to the alternate diet for an additional 67 days. Blood samples were collected at the end of each 67-day period. JustFoodForDogs supplied the whole food diet used in the trial.
RANDOMIZED CLINICAL TRIAL · OPEN ACCESS
Frontiers in Veterinary Science · Vol. 9 · August 2022
Effects of a whole food diet on immune function and inflammatory phenotype in healthy dogs: A randomized, open-labeled, cross-over clinical trial
Authors: Dr. Jared Jaffery, et al.
Midwestern University College of Veterinary Medicine
A 134-day crossover trial in 16 healthy dogs measuring serum acute phase proteins (CRP, haptoglobin, SAA), seven leukocyte cytokines (TNF-α, IL-6, IL-10, GM-CSF, IL-2, IL-8, MCP-1) via canine-specific multiplex assay, and granulocyte/monocyte phagocytic and oxidative burst capacity via flow cytometry — comparing a whole food diet to a commercially available extruded dry diet.
KEY FINDINGS
What the study found
These are the researchers’ published results.
Lower
TNF-α / IL-10 Ratio · P = 0.05
Jaffery et al., Front. Vet. Sci., 2022
Higher
Jaffery et al., Front. Vet. Sci., 2022
No Diff.
Acute Phase Proteins, Phagocytosis & Oxidative Burst
Jaffery et al., Front. Vet. Sci., 2022
Whole food diets “could have immunomodulatory effects in dogs.” The researchers called for follow-up studies in non-healthy dogs to explore the clinical relevance of these findings.
STUDY DESIGN
What the researchers measured
Three categories of immune markers were assessed at the end of each 67-day dietary period. Here’s what each one means.
MEASURE 01
Serum Acute Phase Proteins
Three proteins — C-reactive protein (CRP), haptoglobin (Hp), and serum amyloid-A (SAA) — were measured via ELISA assay. These proteins are produced by the liver in response to immune system activation and are widely used in clinical and research settings as markers of systemic immune status.
MEASURE 02
Leukocyte Cytokine Responses
Whole blood cultures were exposed to three stimuli — a buffer solution (PBS), lipopolysaccharide (LPS from gram-negative bacteria), and lipoteichoic acid (LTA from gram-positive bacteria). A canine-specific multiplex bead-based assay then measured concentrations of seven cytokines: TNF-α, IL-6, IL-10, GM-CSF, IL-2, IL-8, and MCP-1. Cytokines are proteins that direct and coordinate immune cell activity.
MEASURE 03
Granulocyte/Monocyte Immune Function
Flow cytometry was used to evaluate two immune cell functions: phagocytosis — the ability of granulocytes and monocytes to engulf and destroy bacteria — and oxidative burst, the chemical process cells use after engulfing a pathogen. Both were assessed using Escherichia coli as the test organism.
STUDY POPULATION
16 healthy client-owned dogs, confirmed healthy at enrollment via physical exam, complete blood count, serum chemistry profile, and urinalysis.
DIETS COMPARED
A commercially available whole food diet (JFFD Chicken & Rice) versus a commercially available extruded dry diet. Each fed for 67 days in randomized order.
RESEARCHERS' CONCLUSION
Whole food diets “could have immunomodulatory effects in dogs.” The researchers called for follow-up studies in non-healthy dogs to explore the clinical relevance of these findings.
"Whole food diets could have immunomodulatory effects in dogs. Future studies in non-healthy dogs are warranted."
COMMON QUESTIONS
Questions pet parents ask about this study and what it means.
What does "immunomodulatory" mean?
Immunomodulation refers to a change in how the immune system responds to stimuli — either up-regulating or down-regulating specific immune cell behaviors. In this study, researchers observed that dogs fed the whole food diet showed differences in specific cytokine levels and ratios in stimulated immune cell cultures compared to dogs fed the extruded diet. The researchers used the term “immunomodulatory” to describe these observed differences in immune cell response patterns.
What is an inflammatory phenotype?
An inflammatory phenotype describes how a dog’s immune cells tend to respond to stimulation at a given time — specifically, whether they lean toward pro-inflammatory or anti-inflammatory signaling. Researchers characterized this using the ratio of TNF-α (a pro-inflammatory cytokine) to IL-10 (an anti-inflammatory cytokine) measured in leukocyte cultures after stimulation with lipoteichoic acid (LTA). A lower ratio indicates a relative shift toward the anti-inflammatory cytokine.
What is a cytokine, and why does it matter?
Cytokines are small signaling proteins produced by immune cells that coordinate how the immune system responds. Different cytokines serve different roles — some promote inflammation (like TNF-α and IL-6), some reduce it (like IL-10), and some recruit other immune cells to where they’re needed (like IL-8 and MCP-1). Researchers measured seven specific cytokines in this study using a canine-specific multiplex bead-based assay, allowing them to characterize how immune cells from each diet group responded under controlled laboratory conditions.
Why did researchers call for future studies in non-healthy dogs?
The study was conducted in healthy dogs, which establishes a baseline for how immune markers differ between diet types in an otherwise comparable group. Healthy dogs have a different baseline immune profile than dogs managing specific conditions, so follow-up studies in non-healthy dogs would be needed to understand whether these dietary differences in immune cell behavior are clinically meaningful in that context. The researchers’ call for future work reflects standard scientific practice — not a limitation of these findings, but a map for where the research should go next.
What is the significance of the crossover design?
In a standard parallel-group trial, one group receives treatment A and another receives treatment B. Differences between groups can be confounded by individual variation . One group may have had different baseline characteristics. A crossover design eliminates this by having every participant receive both treatments, in randomized order. In this study, each dog served as its own control: any difference observed between the two diet periods reflects the diet itself, not underlying differences between individual animals. This is a methodological strength.
LEARN MORE
Understand the science
Other peer-reviewed research and plain-language guides.
CITATION
Jaffey JA, Su D, Monasky R, Hanratty B, Flannery E and Horman M (2022) Effects of a whole food diet on immune function and inflammatory phenotype in healthy dogs: A randomized, open-labeled, cross-over clinical trial. Front. Vet. Sci. 9:898056. doi: 10.3389/fvets.2022.898056
The research referenced on this page was conducted independently by university researchers. This content is educational only and does not constitute medical or health claims. Consult your veterinarian for guidance specific to your dog’s health needs.