Honey contains flavonoids and phenolic acids, and because of their antioxidant and anti-inflammatory properties, they may play an important role in human health. The purpose of this review was to synthesize the effects of natural honey on pro-and anti-inflammatory cytokines. The effects of honey on wound healing and immunity appear to be inconsistent. The available databases )PubMed and Scopus) were searched and 42 studies were assessed. In patients with cancer, honey has been reported to inhibit the effects of pro-inflammatory factors such as TNF-α and IL-6. In patients with neuro-inflammatory disorders honey has been shown to inhibit the expression of pro-inflammatory markers. It has also been reported that honey can reduce TNF-α expression in conditions associated with liver injury, by suppressing TNF-α converting enzyme activity. Honey inhibits APAP-induced hepatocellular necrosis by modulating the expression of IL-10 and IL-1ß. Animal studies have shown that honey can reduce serum IL-1ß, IL-6 and TNF-α concentration and increase IL-10 concentrations in a model of gastric ulcer. Some studies in diabetics have shown that honey can reduce serum TNF-α, IL-6, IL-1ß and TGF-ß by inhibiting NF-Kß. The source and type of honey and its component have not been indicated in various clinical and practical studies, which are a limitation of these studies, in relation to reproducing them. Sigma, Manuka, Gelam and Tulang honey have been used in most of the in vitro and animal studies. The animal studies have demonstrated similar effects on pro-inflammatory factors, which include reducing serum TNF-α, IL-6 and IL-1β as well as increasing IL-10. There are few human RCTs investigating the effects of honey on inflammatory cytokines. Only one RCT has reported the type of honey that they have used. Tulang honey has been reported to increase serum TNF-α and decrease hs-CRP, which is therefore controversial. Further high-quality studies are needed to firmly establish the clinical efficacy of honey. Because most studies had used different duration, type of honey and dosage, which make them difficult to contextualize, as the phytochemical content of a honey may depend on its source.
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