*2.5. Adverse Events*

In humans, a daily intake of ginger up to four grams is generally considered safe [85]. However, consumption at doses higher than six grams may increase the risk of gastrointestinal disturbances such as gastrointestinal reflux, heartburn, and diarrhoea [86]. In a systematic review of RCTs by Anh [25], 17 of 43 high-quality included trials provided

adverse event information. Heartburn was the most common adverse event reported in 16 studies. Other gastrointestinal disturbances reported with ginger treatment were abdominal pain, bloating, gas, and epigastric distress. None of the events were considered severe [25].

Rare cases of allergic rhinoconjunctivitis were described in the literature concerning occupational exposure to ginger. For instance, Schmidt et al. [87] reported that a 60-year-old woman developed allergic rhinoconjunctivitis with red eyes, sneezing, nasal congestion and a runny nose due to exposure to dust particles containing ginger in her workplace. Similar incidences were reported in other occupational settings as well, with positive skin-prick tests against ginger confirming the reactions to be an immunoglobulin E antibody-mediated allergy [88,89]. The cysteine proteinase GP-I in ginger is thought to be the relevant allergen in these cases [90]. Moreover, occupational allergic contact dermatitis caused by ginger and other spices has also been reported [91]. Hence, ginger could contribute to allergic reactions, especially in patients with known hypersensitivity to spices.

Other potential side effects of ginger, when taken in large doses, may include prolonged pre-existing bleeding, central nervous system depression, and arrhythmia [86]. Therefore, properly dosing concentrated forms of ginger extract and derivatives are essential.
