Bitter apple (Citrullus colocynthis) is a fruit-bearing plant that is believed to possess antioxidant, cytotoxic, antidiabetic, antilipidemic, antimicrobial and anti-inflammatory biological activities (1).
Unfortunately, it has also been described as a highly toxic plant.
Taking colocynth can cause severe irritation of the stomach and intestine lining, bloody diarrhea, kidney damage, bloody urine and inability to urinate. Other serious side effects include convulsions, paralysis and even death.
As a result of its dangers of use, it was banned by the FDA in 1991.
However, due to its potential to prevent and treat several conditions, researchers have not yet given up hope on being able to find more tolerable preparations of this plant to be used in traditional medicine (2).
It is believed the plant’s many promising qualities are due to its rich source of glycosides, flavonoids, alkaloids, fatty acids and essential oils as well as cucurbitacins (a group of phytonutrients linked to many health benefits, especially anticancer effects) (3).
Bitter apple has anti-cancer activity. In a 2007 study published in Biochemical Pharmacology, cucurbitacin glucosides extracted from the leaves of the plant were studied for their effect on human breast cancer cell growth. Researchers discovered that treatment with cucurbitacin glucoside caused changes in the overall cell morphology from an elongated form to a round-shaped cell, indicating that cucurbitacin treatment caused impairment of actin filament organization.
Actin filaments drive cellular communication processes, including cell motility and migration; therefore, impairing the actin filament organization results in inhibition in the transmission of survival signals (4, 5).
Researchers are hopeful with the results and suggest extracted cucurbitacin glucoside might have therapeutic value against breast cancer cells (6).
In another in vitro study, published in the International Journal of Pharmaceutical Sciences Review and Research, scientists set out to evaluate the anti-proliferative and cytotoxic activity of the hydroalcoholic extracts of the plant on adenocarcinoma gastric (stomach cancer) cell lines.
According to their results, the phytochemicals present in the extract of the plant proved toxic to several adenocarcinoma gastric cell lines (7).
Research is ongoing, but scientists believe the plant and its compounds may act as potential chemotherapeutic drugs for the treatment of cancers of the stomach.
Bitter apple has anti-diabetic effect in diabetic rats. A recent experiment was conducted by the department of Pharmacology and Toxicology at Nagpur Veterinary College in India, to determine the efficacy and safety of citrullus colocynthis on treating diabetes. Eighteen rats were used for the study.
Researchers were encouraged to learn that not only did dosing of 50 mg/kg bodyweight and 100mg/kg bodyweight of this plant have an antidiabetic effect, it did not cause toxicity in the rats (8).
Interestingly, in a 2017 study performed on human participants in Iran, researchers found that 125 mg of citrullus colocynthis taken daily by type 2 diabetes patients, lead to considerable decrease in the mean levels of fasting blood sugar and glycated hemoglobin without side effects (9).
Researchers believe that the absence of side effects may be due to the lower dosage of 125 mg. The study lasted two months, therefore, warranting further studies on its efficacy and safety with long-term use.
Bitter apple helps to relieve pain and inflammation associated with osteoarthritis. In an in vitro study, ethanol extract of colocynth root was tested on inflammatory cells similar to those present in osteoarthritis. Osteoarthritis is a common form of arthritis that occurs as a result of the cushioning cartilage at the end of bones wearing away. Symptoms of pain, stiffness, tenderness and loss of flexibility are commonly reported (10).
Researchers observed that ethanol extract of the root reduced levels of pro-inflammatory cytokines in inflamed cells (11). Cytokines are a collection of chemical signals that play a crucial role in generating inflammation in the body.
Researchers are eager to study what effects root extracts of this plant have on the treatment and prevention of other types of inflammation. Chronic inflammation has been connected to the development of coronary artery disease, diabetes, cancer and Alzheimer’s (12).
Bitter apple may help with hair growth. Citrullus colocynthis has long been used in Ayurvedic medicine as a tonic for hair growth, finding itself in some hair loss treatments.
Researchers were intrigued to perform modern studies to learn whether or not petroleum ether and ethanol extract of this plant could grow hair in albino rats.
The extracts were added to an oily ointment base and applied to the shaved skin of the rats, while a 2 percent solution of Minoxidil (the standard hair loss treatment) was also applied for comparison.
The results were quite promising: Hair growth initiation time was significantly reduced to half on treatment with the extracts. The time required for complete hair growth was also considerably reduced. In addition, the treatment was successful in bringing a greater number of hair follicles (13).
Bitter apple can cause severe side effects, namely intestinal damage and lesions associated with bleeding.
In 1989, three cases of toxic acute colitis following ingestion of citrullus colocynthis were reported. The main clinical presentation was dysenteric diarrhea (severe diarrhea with blood). The colonoscopic observations were mucosal congestion and hyperemia with abundant exudates, but no ulceration or pseudopolyp formation.
Symptoms disappeared within 14 days of stopping use in all patients.
There was also another report in 1996 of colocynth poisoning as a rare cause of acute diarrhea syndrome. Five cases of toxicity due to consumption of colocynth in Saudi Arabia over a two-year period was also reported (14). The cases presented with acute severe bloody diarrhea.
Due to its association with severe side effects, and its ban by the FDA, there is no recommended dosage of bitter apple.
Bitter apple is an herbal plant with a seemingly unending list of medicinal uses as well as pharmaceutical and nutraceutical potential. While lab studies show its antioxidant, cytotoxic, antidiabetic, antilipidemic, antimicrobial and anti-inflammatory biological activities, the dangerous and deadly side effects that have been reported in animal and human studies, makes it unsafe for use.
Oral supplementation of bitter apple (citrullus colocynthis) was banned by the FDA in 1991.
Researchers have not given up hope on finding a safe preparation of the plant for possible future use in traditional medicine.