The Dietary Intake of Carrot-Derived Rhamnogalacturonan-I Accelerates and Augments the Innate Immune and Anti-Viral Interferon Response to Rhinovirus Infection and Reduces Duration and Severity of Symptoms in Humans in a Randomized Trial

Abstract

Acute respiratory infections are an important health concern. Traditionally, polysaccharide-enriched extracts from plants, containing immunomodulatory rhamnogalacturonan-I (RG-1), were used prophylactically. We established the effects of dietary supplementation with carrot-derived RG-I (cRG-I, 0–0.3–1.5 g/day) in 177 healthy individuals (18–65 years) on symptoms following infection with rhinovirus strain 16 (RV16). Primary outcomes were changes in severity and duration of symptoms, and viral load in nasal lavage. Secondary outcomes were changes in innate immune and anti-viral responses, reflected by CXCL10 and CXCL8 levels and cell differentials in nasal lavage. In a nested cohort, exploratory transcriptome analysis was conducted on nasal epithelium. Intake of cRG-I was safe, well-tolerated and accelerated local cellular and humoral innate immune responses induced by RV16 infection, with the strongest effects at 1.5 g/d. At 0.3 g/d, a faster interferon-induced response, induction of the key anti-viral gene EIF2AK2, faster viral clearance, and reduced symptom severity (−20%) and duration (−25%) were observed. Anti-viral responses, viral clearance and symptom scores at 1.5 g/d were in between those of 0 and 0.3 g/d, suggesting a negative feedback loop preventing excessive interferon responses. Dietary intake of cRG-I accelerated innate immune and antiviral responses, and reduced symptoms of an acute respiratory viral infection.

Ingestion, Immunity, and Infection: Nutrition and Viral Respiratory Tract Infections

“…It has now become clear that RG-I fibers from various plant sources have a modulating effect on immune function and on the microbiota ( 225 , 226 ). A recent randomized controlled trial explored a low or a higher dose of cRG-I from carrot as a dietary supplement in heathy volunteers ( 227 ). After 8 weeks, the volunteers were infected with a low dose of rhinovirus in their nasal cavity and then the immune response and the development of cold symptoms were monitored.…”

“…Such studies in which the effect of a nutritional intervention on the course after a (viral) challenge is measured in humans are seen as particularly relevant by experts and regulators ( 228 , 229 ). Consumption of cRG-I was found to greatly accelerate the anti-viral IFN response in infected nasal epithelium and the local innate immune response, resulting in a significantly milder clinical course with less severe and shorter cold symptoms ( 227 ).…”

Effects of Dietary Supplementation with Carrot-Derived Rhamnogalacturonan-I (cRG-I) on Accelerated Protective Immune Responses and Quality of Life in Healthy Volunteers Challenged with Rhinovirus in a Randomized Trial

“…This single center, randomized, double-blind, placebo-controlled dose response study had three arms with 0, 0.3 g/day (d) and 1.5 g/d cRG-I in a parallel design. Details on design, adverse events, safety monitoring, disposition of subjects and primary outcome have been described earlier [ 13 ]. The study period comprised four periods: enrolment (screening, eligibility), dietary supplementation for 8 weeks, response to RV16 infection (exposure on day 0, d0) with continued supplementation for 2 weeks, and 3-week follow-up without supplementation ( Figure 1 ).…”

“…Recently we demonstrated that dietary intake of carrot-derived RG-I accelerates and augments the innate immune and anti-viral interferon responses to an infection with rhinovirus strain 16 (RV16) and reduces the duration and severity of symptoms in healthy volunteers [ 13 ].…”

“…In this paper we elaborate on the initial findings that dietary intake of cRG-I accelerates innate immune responsiveness and reduces severity and duration of symptoms during a RV16 infection in humans [ 13 ]. We also zoom in on the individual symptoms and quality of life attributes affected and show that supplementation with cRG-I not only accelerates local immune responsiveness to the respiratory infection but can also modulate immune responsiveness of cells from the systemic compartment, measured following an ex vivo challenge.…”