Four weeks of spice consumption lowers plasma proinflammatory cytokines and alters the function of monocytes in adults at risk of cardiometabolic disease: secondary outcome analysis in a 3-period, randomized, crossover, controlled feeding trial

Abstract

Background: Numerous studies demonstrate acute anti-inflammatory properties of individual spices, but none have examined the effect of longer-term consumption of a spice blend incorporated in a meal.

Objectives: We investigated the effect of longer-term spice consumption on inflammatory cytokines and monocyte subsets [classical (CM), intermediate (IM), nonclassical (NCM)] in adults at risk of cardiometabolic disease.

Methods: A 3-period, randomized, crossover, controlled feeding trial was conducted. Participants (n = 71 recruited; n = 63 completed) randomly consumed diets differing in terms of the quantity of spices: 0.547 g (low-dose spice diet; LSD), 3.285 g (medium-dose spice diet; MSD), or 6.571 g (high-dose spice diet; HSD) · d-1 · 2100 kcal-1, for 4 wk with a ≥2-wk washout between diets. At baseline and after each diet period, proinflammatory cytokines (IL-1β, IL-6, IL-8, monocyte chemoattractant protein-1, and TNF-α) in plasma and LPS-stimulated peripheral blood mononuclear cell culture supernatants, and the phenotype and function of monocyte subsets, were measured in fasted participants. Postprandial proinflammatory cytokines also were quantified at baseline by consumption of a low-spice-dose test meal, and after each diet period by consumption of a test meal containing a spice dose corresponding to daily spice consumption during the preceding 4-wk diet period.

Results: Fasting plasma IL-6 was reduced (mean ± SEM: -118.26 ± 50.63 fg/mL; P < 0.05) after MSD compared with baseline. Postprandial plasma IL-1β, IL-8, and TNF-α were lower (mean ± SEM : -9.47 ± 2.70 fg/mL, -0.20 ± 0.05 pg/mL, and -33.28 ± 12.35 fg/mL, respectively) after MSD compared with LSD (main diet effect; P < 0.05). CM adherence was reduced (mean ± SEM: -0.86 ± 0.34; P = 0.034) after HSD compared with LSD. IM migration was reduced after MSD and HSD compared with LSD (mean ± SEM: -0.39 ± 0.09 and -0.56 ± 0.14, respectively; P < 0.05).

Conclusions: Four weeks of MSD consumption reduced fasting plasma IL-6 and postprandial plasma IL-1β, IL-8, and TNF-α as well as altering monocyte function.This trial was registered at clinicaltrials.gov as NCT03064932.

Keywords: cardiovascular disease; inflammatory cytokines; monocytes; nutritional intervention; randomized controlled trial.

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1

Study design used to examine the effect of consuming an LSD, MSD, and HSD for 4 wk in adults at risk of cardiometabolic disease. HSD, high-dose spice diet; LSD, low-dose spice diet; MSD, medium-dose spice diet.

FIGURE 2

Change in plasma IL-1β (A), IL-6 (B), IL-8 (C), MCP-1 (D), and TNF-α (E) concentrations and change in IL-1β (F), IL-6 (G), IL-8 (H), MCP-1 (I), and TNF-α (J) secretion from LPS-stimulated peripheral blood mononuclear cells after consuming an L, M, and H for 4 wk in fasted adults at risk of cardiometabolic disease. Labeled means without a common letter differ, P < 0.05. *Significant change from baseline, P < 0.05. Data are mean ± SEM. n = 63. H, high-dose spice diet; L, low-dose spice diet; M, medium-dose spice diet; MCP, monocyte chemoattractant protein.

FIGURE 3

Change in postprandial plasma IL-1β (A), IL-6 (B), IL-8 (C), MCP-1 (D), and TNF-α (E) concentrations after test meal ingestion after LSD, MSD, and HSD consumption for 4 wk in adults at risk of cardiometabolic disease. Data are mean ± SEM. n = 43. HSD, high-dose spice diet; LSD, low-dose spice diet; MCP, monocyte chemoattractant protein; MSD, medium-dose spice diet.

FIGURE 4

Change in the percentage of monocyte subsets after consuming L, M, and H for 4 wk in fasted adults at risk of cardiometabolic disease. (A) Representative dot plot of CD14 and CD16 expression and the gate of monocyte subsets. (B–D) Change in the percentages of (B) CMs, (C) IMs, and (D) NCMs after spice consumption. Labeled means without a common letter differ, P < 0.05. *Significant change from baseline, P < 0.05. Data are mean ± SEM. n = 23. CM, classical monocyte; H, high-dose spice diet; IM, intermediate monocyte; L, low-dose spice diet; M, medium-dose spice diet; NCM, nonclassical monocyte.

FIGURE 5

Correlation between the percentage of foamy monocytes and the expression of CD11c on total monocytes (A), CMs (B), IMs (C), and NCMs (D) and change in the percentage of foamy monocytes in monocyte subsets (E) and their surface expression of CD11c (F) after consuming L, M, and H for 4 wk in fasted adults at risk of cardiometabolic disease. Labeled means without a common letter differ, P < 0.05. *Significant change from baseline, P < 0.05. Data are mean ± SEM. n = 12. CM, classical monocyte; H, high-dose spice diet; IM, intermediate monocyte; L, low-dose spice diet; M, medium-dose spice diet; MFI, mean fluorescence intensity; NCM, nonclassical monocyte.

FIGURE 6

Change in the expression of CCR2 on CMs (A), IMs (B), and NCMs (C), in the adherence of monocyte subsets to HUVECs (D), and in the trans-endothelial migration of monocyte subsets through HUVECs (E) after consuming L, M, and H for 4 wk in fasted adults at risk of cardiometabolic disease. Labeled means without a common letter differ, P < 0.05. *Significant change from baseline, P < 0.05. Data are mean ± SEM. CCR2, n = 23. Adherence and migration indexes, n = 6. CCR2, C-C chemokine receptor type 2; CM, classical monocyte; H, high-dose spice diet; HUVEC, human umbilical vein endothelial cell; IM, intermediate monocyte; L, low-dose spice diet; M, medium-dose spice diet; MFI, mean fluorescence intensity; NCM, nonclassical monocyte.