Sulforaphane as a potential modifier of calorie-induced inflammation: a double-blind, placebo-controlled, crossover trial

Abstract

Background and aims: Observational data indicate that diets rich in fruits and vegetables have a positive effect on inflammatory status, improve metabolic resilience and may protect against the development of non-communicable diseases. Nevertheless, experimental evidence demonstrating a causal relationship between nutrient intake (especially whole foods) and changes in metabolic health is scarce. This study investigated the pleiotropic effects of sulforaphane from broccoli sprouts, compared to pea sprouts, on biomarkers of endothelial function, inflammation and metabolic stress in healthy participants subjected to a standardized caloric challenge.

Methods: In this double-blind, crossover, randomized, placebo-controlled trial 12 healthy participants were administered 16 g broccoli sprouts, or pea sprouts (placebo) followed by the standardized high-caloric drink PhenFlex given to disturb healthy homeostasis. Levels of inflammatory biomarkers and metabolic parameters were measured in plasma before and 2 h after the caloric overload.

Results: Administration of broccoli sprouts promoted an increase in levels of CCL-2 induced by caloric load (p = 0.017). Other biomarkers (sICAM-1, sVCAM-1, hs-CRP, and IL-10) individually showed insignificant tendencies toward increase with administration of sulforaphane. Combining all studied biomarkers into the systemic low-grade inflammation score further confirmed upregulation of the inflammatory activity (p = 0.087) after sulforaphane. No significant effects on biomarkers of metabolic stress were detected.

Conclusion: This study has demonstrated that sulforaphane facilitated development of a mild pro-inflammatory state during the caloric challenge, which could be suggestive of the onset of the hormetic response induced by this phytonutrient. The use of integrative outcomes measures such as the systemic low-grade inflammation score can be viewed as a more robust approach to study the subtle and pleiotropic effects of phytonutrients.Clinical trial registration:www.clinicaltrials.gov, identifier NCT05146804.

Keywords: biomarkers; diet; glucoraphanin; hormesis; inflammation; nutrients; phenotypic flexibility; sulforaphane.

Figure 1

Schematic presentation of a study visit. Administration of intervention (sulforaphane/placebo) was followed in 90 min by administration of standardized caloric challenge PhenFlex. Blood samples were obtained before (90 min) and 2 h after (210 min) PhenFlex challenge.

Figure 2

CONSORT flow diagram.

Figure 3

Plasma concentrations of sICAM-1 (pg/mL) and sVCAM-1 (pg/mL) in the sulforaphane and placebo groups before, after, and the changes during the PhenFlex challenge (A-D). Data are presented as boxplots [median, interquartile range, outliers (circles)]. Timepoints: 1—before administration of PhenFlex (90 min); 2—2 h after PhenFlex (210 min). Comparison between timepoints in sulforaphane/placebo.

Figure 4

Plasma concentrations of CCL-2 (pg/mL) in the sulforaphane and placebo groups before, after, and the changes during the PhenFlex challenge (A,B). The systemic low-grade inflammation score (SIS) in the sulforaphane and placebo before and after the PhenFlex challenge (C). Data are presented as boxplots [median, interquartile range, outliers (circles)]. Timepoints: 1—before administration of PhenFlex (90 min); 2—2 h after PhenFlex (210 min). Comparison between timepoints in sulforaphane/placebo, *p < 0.05.

Figure 5

Hormesis hypothesis on health effects of fruits and vegetables. Changes in integrative anti-inflammatory capacity in response to intervention, followed by caloric load. The dotted lines represent the expected sustained effects on integrative anti-inflammatory potential through an increase in endogenous antioxidants via Nrf2 activation by hormetins. Black: Broccoli sprouts (with sulforaphane); Gray: Pea sprouts (without sulforaphane); T0 and T1—time points of blood sampling.