Dark chocolate attenuates intracellular pro-inflammatory reactivity to acute psychosocial stress in men: A randomized controlled trial

Brain Behav Immun. 2016 Oct;57:200-208. doi: 10.1016/j.bbi.2016.04.006. Epub 2016 Apr 28.


Flavanol-rich dark chocolate consumption relates to lower risk of cardiovascular mortality, but underlying mechanisms are elusive. We investigated the effect of acute dark chocolate consumption on inflammatory measures before and after stress. Healthy men, aged 20-50years, were randomly assigned to a single intake of either 50g of flavanol-rich dark chocolate (n=31) or 50g of optically identical flavanol-free placebo-chocolate (n=34). Two hours after chocolate intake, both groups underwent the 15-min Trier Social Stress Test. We measured DNA-binding-activity of the pro-inflammatory transcription factor NF-κB (NF-κB-BA) in peripheral blood mononuclear cells, as well as plasma and whole blood mRNA levels of the pro-inflammatory cytokines IL-1β and IL-6, and the anti-inflammatory cytokine IL-10, prior to chocolate intake as well as before and several times after stress. We also repeatedly measured the flavanol epicatechin and the stress hormones epinephrine and cortisol in plasma and saliva, respectively. Compared to the placebo-chocolate-group, the dark-chocolate-group revealed a marginal increase in IL-10 mRNA prior to stress (p=0.065), and a significantly blunted stress reactivity of NF-κB-BA, IL-1β mRNA, and IL-6 mRNA (p's⩽0.036) with higher epicatechin levels relating to lower pro-inflammatory stress reactivity (p's⩽0.033). Stress hormone changes to stress were controlled. None of the other measures showed a significant chocolate effect (p's⩾0.19). Our findings indicate that acute flavanol-rich dark chocolate exerts anti-inflammatory effects both by increasing mRNA expression of the anti-inflammatory cytokine IL-10 and by attenuating the intracellular pro-inflammatory stress response. This mechanism may add to beneficial effects of dark chocolate on cardiovascular health.

Keywords: Cytokines; Dark chocolate; IL-10; IL-1β; IL-6; Inflammation; NF-κB; Stress reactivity; TSST; mRNA.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Catechin / blood
  • Chocolate*
  • Epinephrine / metabolism
  • Flavonols / administration & dosage
  • Flavonols / pharmacology*
  • Humans
  • Hydrocortisone / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism*
  • Interleukin-1beta / blood*
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • NF-kappa B / blood*
  • Stress, Psychological / drug therapy
  • Stress, Psychological / metabolism*
  • Young Adult


  • Anti-Inflammatory Agents
  • Flavonols
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • Catechin
  • Hydrocortisone
  • Epinephrine