Citrullus colocynthis, also known as bitter cucumber, is a fruit-bearing plant. Low doses of its seeds and fruit can reduce blood glucose levels. Higher doses are associated with side-effects like colonic inflammation and rectal bleeding.
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Primary Information, Benefits, Effects, and Important Facts
Citrullus colocynthis, also known as bitter cucumber, is a fruit-bearing plant sometimes used medicinally.
Citrullus colocynthis is used to treat diabetes, since it may be able to induce insulin secretion from the pancreas after supplementation, while reducing blood glucose and improving lipid levels.
Preliminary evidence suggests a topical application of Citrullus colocynthis may stimulate hair growth, with an effect comparable to finasteride, a male pattern baldness drug. More evidence is needed to confirm this effect.
Even low doses (100mg, taken three times) of Citrullus colocynthis can cause diarrhea, while higher doses (1,500 mg) can cause colonic inflammation and rectal bleeding. These side-effects stop once supplementation is ceased.
Since the bioactive compounds in Citrullus colocynthis are still unknown, and even low-dose supplementation is associated with intestinal side-effects, Citrullus colocynthis is not recommended for oral supplementation.
While the toxicity is reversible within two weeks, consumption of over a gram of the fruits or seeds (dry weight basis) results in intestinal inflammation and rectal bleeding; it is not known if long term damage occurs from this
Limited human evidence suggests that 100mg of the seed or dry pulp extract, taken three times a day for a total daily dose of 300mg, is associated with reducing blood glucose and improving lipid levels.
The traditional ‘recommended’ dose for Citrullus colocynthis is 300-800mg. This dosage range is associated with severe intestinal inflammation.
Human Effect Matrix
The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects citrullus colocynthis has on your body, and how strong these effects are.
Grade
Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
?
The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome
Magnitude of effect
?
The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
?
Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
May decrease blood glucose in diabetics at low doses, but the evidence at this moment in time is limited (due to differences between groups at the start of the study)
The decrease seen in triglycerides in one study was statistically significance, but the average reduction in hyperlipidemics (16%) has a very large range
Citrullus colocynthus (of the family Cucurbitaceae) is a fruit bearing plant known traditionally mainly due to its potency as a hydragogue (causes water accumulation in the colon) and catharsis (induces defecation) producer in humans when consumed at more than two grams dry fruit weight[1] and other traditional usages being for the treatment of rheumatism, stimulating the immune system, tuberculosis, diabetes, and analgesic.[2] Oral ingestion of the fruit at doses lower than this (300-800mg daily) tends to be prescribed in some middle eastern locations for the treatment of diabetes to avoid the intestinal side-effects.[1]
Traditionally, most names for this plant have pertained to its bitterness. It has the names of 'bitter thing' (Algham and Sharang), 'bitter cucumber' (khiar talkh), and 'bitter melon' (kharboze talkhak),[3] but should not be confused with the plant momordica charantia which has the name of bitter melon or bitter gourd. Furthermore, a dry resin of this plant has traditionally been referred to as citrulline,[4] which should not be confused with the amino acid L-Citrulline and may have given rise to a mistaken idea that the amino acid was a laxative (compounded with the potential laxative properties of the related amino acid, L-Arginine, when consumed in high doses).
Citrullus colocynthis is a medicinal herb used mostly for the treatment of diabetes and inflammatory diseases, while it is most well known for its bitter taste and the diarrhea it can cause when consumed as a food product; it is unrelated to the amino acid L-citrulline
1.2. Composition
The seeds of citrullus colocynthis are known to possess:
567.32kcal per 100g dry weight[5] or lower, since this study found the highest known lipid content in the seeds and others suggest that it is a lower concentration (which would reduce calories)
17-23% fatty acids by dry weight[6][7] (one study noted 50% lipids[5]) of which a low amount of free fatty acids (1.57% total seed weight and 7% total oil[6]) and both triglycerides and free fatty acids comprise mostly linoleic acid (66-76.4%), palmitic acid (6.3-8.1%), oleic acid (7.8-14.2%), and stearic acid (6.1-7.3%);[7][6] it appears to have high heat tolerance assessed by low lipid peroxidation values[6][5]
Vitamin E at 121.85mg/100g[6] with a high γ-tocopherol content (116.36+/-0.15mg/100g; 95% total vitamin E) and lower α (0.72+/-0.06mg/100g), β (0.57+/-0.03mg/100g), and δ (4.19+/-0.12mg/100g) content[6]
The seeds of this plant are fairly balanced in the macronutrient profile (like most seeds in the cucurbitaceae family) and the oil derived from these seeds is very high in both omega-6 fatty acids and in the form of vitamin E that is seen as more desirable for supplementation (γ-tocopherol, although there does not appear to be a significant γ-tocotrienol content)
Cucurbitacin E glucose (0.05% dry weight[8]) and I glucoside (0.01% dry weight[8])
The fruits appear to, on the equivalent of dry mass, contain a 0.74% phenolic content (gallic acid equivalents or GAEs) and a 0.13% flavonoid content (catechin equivalents).[9] The seeds also contain flavonoids and polyphenolics.[10]
It is said that the potency of this plant starts to decay when the fruit is opened, and is lost within two years;[3] suggesting the main bioactive is unstable.
The unique bioactive molecules in the fruit pulp, the main medicinal component of this plant, are not well known
2Cardiovascular Health
2.1. Cholesterol
100mg of citrullus colocynthus thrice daily for two months in type II diabetes has failed to significantly modify any measured parameter of cholesterol metabolism (LDL-C, HDL-C, or total cholesterol)[1] although total cholesterol can be reduced if the same dose of the seed extract is given to hyperlipidemics (17.57+/-39.55mg/dL; average 8.6% reduction);[11] the alterations in HDL-C (2.41+/-5.63mg/dL; average 5.4% increase) and LDL-C (7.33+/-30.34mg/dL; average 6.3% reduction) also showed promise, but were statistically insignificant.[11]
May reduce cholesterol in those with high cholesterol, but the one study to find this occurring in humans noted a remarkable degree of variance. More studies would be needed to confirm if this variance is true or not, since the two studies conducted at this moment in time are less than ideal (methodologically speaking)
2.2. Triglycerides
100mg of citrullus colocynthus thrice daily for two months in type II diabetes has failed to significantly reduce triglycerides.[1] The seed powder at the same dose (100mg) of the mature seed extract has managed to reduce triglycerides in hyperlipidemic persons after six weeks, but the reductions (31.52+/-73.98mg/dL; average of 16% reduction) was very unreliable in magnitude.[11]
The reduction in triglycerides managed to reach statistical significance, but this was also associated with huge variance in how much triglycerides were reduced
3Interations with Glucose Metabolism
3.1. Insulin
Citrullus colocynthis has been traditionally used as a medicinal plant for diabetes[12] thought to be related to being an insulin releasing agent of sorts;[13] this has been noted in vitro[14] and in vivo as acute oral ingestion of 300mg/kg of the pulp (ethanolic extraction) to rats has been noted to increase serum insulin AUC by 59.5% alongside a reduction in glucose (33%)[15] and has elsewhere this extraction has been noted to increase insulin content of pancreatic β-cells.[16]
Higher than normal doses (potentially within the toxic range) appear to have an ability to stimulate insulin secretion from the pancreas. The bioactive that does this is currently not known
When looking at rodent studies, citrullus colocynthis (8% of the seed oil) has been found to preserve β-cell structure in streptozotocin induced diabetic rats relative to control, and outperformed oils from sunflower and olive at preserving insulin sensitivity.[7]
When the oil is isolated, it appears to be more protective of pancreatic β-cells (that secrete insulin) than other dietary oils during diabetes
3.2. Type II Diabetes
In type II diabetics given 100mg of the dried fruit extract thrice daily (totalling 300mg) for a period of two months noted significant reductions in blood glucose (8.2%) and HbA1c (13.5%) while insulin was not measured; these two parameters, however, were significantly higher at baseline in the experimental group relative to placebo.[1]
One human study has noted improvements in fasting blood glucose and HbA1c associated with supplementation of the fruit pulp (insulin not measured), but there were differences at baseline which may have influenced the results observed
4Peripheral Organ Damage
4.1. Kidney
Oral ingestion of 25mg/kg citrullus colocynthis daily to rats also given the nephrotoxin gentamicin has noted that supplementation failed to protect the rats from nephrotoxicity (assessed by necrosis of tulubes) despite causing an apparently beneficial change in serum biomarkers of creatinine and BUN.[17]
Has once failed to exert kidney protective effects despite having an antioxidant property to it
5Interactions with Cancer
5.1. Liver Cancer
In isolated HepG2 carcinoma cells, cucurbitacin glucosides (I and E) have cytotoxic activity with IC50 values of 3.5μM and 2.8μM respectively.[8]
6Interactions with Aesthetics
6.1. Hair
A petroleum ether extract (3.23% yield) of the fruits of citrullus colocynthis at 2-5% given to mice alongside testosterone injections (to induce male-pattern baldness) for three weeks appears to induce hair follicle density with a potency nonsignificantly greater than a 2% finasteride solution.[18] this may be related to a 5α-reductase inhibitory effect of this plant.[19]
Possible hair growth stimulating properties, which may be of larger magnitude in men with male pattern baldness due to also possessing a 5α-reductase inhibitory potential
7Safety and Toxicology
7.1. General
Citrullus colocynthis is traditionally known as both a medicinal plant and a toxic plant,[20] and in animals high doses of the fruits or leaves of citrullus colocynthis have been noted to possess toxicity towards various animals such as sheep[21] and chicks;[22] these changes are associated mostly with intestinal damage and lesions associated with bleeding,[23] but may be reversible with removal of the food product from the diet.[22]
There are various case studies where consumption of high levels of citrullus colocynthis have resulted in intestinal damage such as pseudomembranous colitis (mistaking a citrullus colocynthis fruit as a zucchini),[24] acute colitis,[25] and anal bleeding (single dose of 1,500-1,600mg of the dried fruits or consumption of a tea made from the plant).[26][27] These symptoms may be reversible in as little as two weeks of cessation.[25][26]
Although it is reversible, there appears to be intestinal and liver toxicity associated with inflammation and rectal bleeding with 'high' doses of the supplement. In regards to 'high', that is relative to the recommended dose (300-800mg) since these negative effects have occurred with less than two grams of the dried fruit weight
7.2. Human Toxicology
When using 100mg of the dried fruits thrice daily (total dose of 300mg) for a period of two months, it was noted that only 13% of participants reported mild diarrhea at the start of the study which dissipated near the end of the study; there were no other alterations in biochemical or clinical parameters indicating toxicity;[1] this lack of alterations in toxicity (assessed by liver enzymes SGOT and SGPT) has been replicated with 100mg of the seed extract thrice daily for six weeks in hyperlipidemics.[11]
Two studies have failed to note toxicity with citrullus colocynthis when the oral dose is kept below 300mg of either the seed or fruit dry weight daily, with only minor diarrhea that fades with time
