I want to drink orange juice every morning, but years ago it hurt my gut when I had severe inflammation. I wonder if it’s from the citric acid? I have also read that citrus fruits are “histamine liberators”, and I have problems with histamine.
I couldn’t find any articles about
the “histamine liberator” concept; just some website claims. I would like to read studies on it, if you know of any.
I know citric acid can contribute to the inflammation.
Citrate as an Inflammatory Signal
While the role of other metabolites as inflammatory signals has been well discussed (21, 22) citrate also plays a role in key inflammatory pathways (Figure (Figure2).2). In M1 macrophages, there is an increased isocitrate:αKG ratio and transcript
ional downregulation of Idh1 (47). This break was also seen in DCs (34). With increased glycolytic flux in both activated DCs and macrophages and a break in the Krebs cycle, pyruvate derived from glucose feeds into Krebs cycle but cannot continue past citrate/isocitrate. An increase in the levels of citrate is detected in both mouse (LPS-stimulated) and human [tumour necrosis factor α (TNFα)- or interferon-γ (IFNγ)-stimulated] macrophages (24, 48). This coincides with upregulation of CIC and ACLY, both of which occur in an NF-κB-dependent manner where LPS or TNFα is used to activate the cells, or IFNγ can also induce CIC and ACLY via STAT1 (32, 49). The export and breakdown of mitochondrial citrate has been linked to the production of several important pro-inflammatory mediators in macrophages, namely NO, ROS, and prostaglandin E2 (PGE2) production in human macrophages (32, 48, 49). Inhibition of CIC activity or its genetic silencing with siRNA leads to a marked reduction in NO, ROS, and PGE2 production in LPS and cytokine-stimulated macrophages. Infantino et al. suggest that the decrease in PGE2 production is due to a decreased availability of precursors for PGE2 synthesis as adding exogenous acetate rescues the effect of CIC inhibition on PGE2 productions. Acetate can be converted to acetyl-CoA by acetyl-CoA synthase (ACSS) (50). Inhibition of fatty acid synthase (FASN) with C75 in DCs also reduced LPS-induced PGE2 (34). Endogenous PGE2 is essential for the production of LPS-induced pro-IL1β (51). This implies that citrate may be critical to IL1β production.
Front Immunol. 2018; 9: 141.
A Role for the Krebs Cycle Intermediate Citrate in Metabolic Reprogramming in Innate Immunity and Inflammation
Niamh C. Williams and Luke A. J. O’Neill https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5807345/
Does OJ cause any gut related issues for you?
Does the ripeness of the oranges make any difference in terms of its effects?