Dandelion

Taraxacum officinale (of the family Asteraceae) is the botanical name for the common dandelion, commonly considered an invasive plant species^[1][2] and botanically related to chicory.^[3] The genus of Taraxacum comprises types of dandelion, with other species that have been used traditionally or medicinally including taraxacum mongolicum (Chinese kidney formulation^[4]) and Taraxicum coreanum^[5] with the species known as Taraxacum erythrospermum also being considered a weed like officinale. Other popular names for this plant include the french name pisselent (in reference to its diuretic properties), lion's tooth, and milk daisy.^[3]

It has some traditional usage in Korean medicine for improving general health and energy levels^[6] and some other uses such as a cholerectic, for treatment of rheumatism,^[7] and lactation aid^[6] but is most commonly known for its traditional usage as a diuretic today.^[8]

Dandelion is also considered a food product, being used primarily in salads, where the root can be roasted as a supposed coffee substitute.^[3]

Dandelion is a plant most commonly known overall for being an invasive plant species, but medicinally is sometimes used for various general health purposes such as vitality and the treatment of a wide range of inflammatory conditions. Most practically and most prolifically, it is used as a diuretic.

Dandelion is known to contain:

• Eudesmanolides (sesquiterpene lactones) and their glucosides, formerly collectively known as taraxacum^[3] and found in most dandelion species^[9][10] including officinale^[11] contributing to their bitter taste^[3] and likely its allergenic potential.^[12][13] Ones found in Taraxacum officinale include 4-O-β-D-glucosyl-11,13-dihydro-taraxinic acid and 14-O-β-D-glucosyl-taraxinic acid.^[14]
• The pentacyclic terpenoid known as taraxasterol,^[15] considered a main bioactive of dandelion and named after its genus (Taraxacum)^[16] although fairly ubiquitous as it can be found in other herbs such as Eupatorium azureum,^[17] Stevia berlandieri,^[18] Capparis sepiaria,^[19] and Cirsium texanum^[20][18]
• Aesculin (the major bioactive of Horse chestnut) at 0.015-5.32mg/g in two month old dandelions and 0.094-21.44mg/g in six month old samples^[21]
• Polysaccharides designated Taraxicum officinale 1 (TOP1 at 37.2% of the dry weight of a hot water extract^[22]) and Taraxicum officinale 2 (TOP2 at 11.3%^[22])^[23]
• A series of antimicrobial peptides known as Taraxicum officinale antimicrobial peptides (ToAMPs) numbering from one (ToAMP1)^[24] to ToAMP4^[25]
• Inulin (dietary fiber) comprises of mostly fuctooligosaccharids (kestose, mystose, and fuctofuranosylnystose)^[26] which may confer probiotic effects^[27]
• Nitrate averaging 195-202mg/kg^[28][29] (range of 47-487mg/kg^[28])
• Chicoric acid (Named after chicory, a botanically related herb to dandelion^[3]) at 18.9µg/g in a hot water extract of the aerial parts of the plant and a higher content (128.6µg/g) in a methanolic extract.^[30] The plant itself appears to have 14.91mg/g dry weight of the leaves, 13.79mg/g in the flowers, and a mere 2.71mg/g in the roots^[31]
• Luteolin^[32] at 4.80µg/g (leaves^[33]) and as 7-O-glucoside (990µg/g dry weight in leaves with none detectable in roots.^[34]) Extracts of dandelion have found 3.53µg/g in the water extract but a higher concentration of 34.2µg/g in a methanolic extract^[30] while ethyl acetate extracts may be up to 10% luteolin plus luteolin-7-O-glucoside collectivley^[35]
• Myricetin at 170µg/g in a commercial product and not detectable in roots nor leaves of wild dandelion tested^[34]
• Chlorogenic acid^[32] at 700-770µg/g in leaves and higher at 4.33mg/g in roots,^[34] although another study failed to find any in the leaves and only 0.54mg/g dry weight in the roots.^[31]
• Caffeic acid^[32] at 1.1-1.19mg/g in roots and 19.06mg/g in a leaf extract^[34]
• Hesperidin at 870µg/g in roots (none detected in a commercial product) and none in leaves^[34]
• Isovitexin at 870µg/g in leaves only and vitexin as 2-rhamnoside at 150-990µg/g in roots and higher at 2.07mg/g in the leaves^[34]
• Anthocyanins as cyanidin-3-glucoside at 2.56mg/g dry weight (leaves) and 7.79mg/g (flower) with none detectable in the root^[31]
• Kynurenic acid at 0.05+/-0.01µg/g (root^[7])
• Phenylacetic acid derivatives (root)^[36]
• Potassium in varying ranges of 23.3-59.9mg/g (medican figures of around 42.5-45.1mg/g) in the leaves^[37][38] with roots having about half the content (24.5mg/g or 2.45%^[37])
• Sodium at 0.49% and 0.33% of the leaves and roots respectively^[37]
• Calcium at 0.88% and 0.33% of the leaves and roots respectively^[37]
• Copper in varying concentrations (depending on the soil it is grown in) of 15-97µg/g (roots) and 15-52µg/g (leaves), about half of the soil content of copper and well correlated with the soil content^[39]
• Manganese in varying concentrations (depending on the soil it is grown in) of 43-115µg/g (roots) and 32-98µg/g (leaves)^[39]
• Zinc in varying concentrations (depending on the soil it is grown in) of 59-265µg/g (roots) and 40-150µg/g (leaves)^[39]
• Lead in varying concentrations (depending on the soil it is grown in) of up to 155µg/g (roots) and up to 28µg/mL (leaves), with some samples showing negligible content^[39]
• Chromium in varying concentrations (depending on the soil it is grown in) of up to 10µg/g (roots) and up to 5µg/g (leaves) with some samples showing negligible content^[39]

There are a wide variety of molecules found in dandelion which, for the most part, are not unique nor high enough to put this herb above others that have higher concentrations of the same flavonoids or potent unique molecules. Of the ones in dandelion which may be potent and unique we have two polysaccharides (TOP1 and TOP2) which are likely present in the water extract amongst other things, and some sesquiterpenes that may contribute to the effects of ethanolic extracts

The overall flavonoid content of dandelion is higher in the dry leaf extract (27.32mg/g or 2.7%, although other studies have found significantly lower levles of 8mg/g chlorogenic acid equivalents^[33]) than in root extracts (3.03-3.10mg/g or 0.3%)^[34] and a hot water extract (three subsequent extractions at 100°C in 200mL of water for 3 hours, 150mL for 2 hours, and 100mL for a final hour) yields 17% of the dandelion's initial dry weight as the water soluble extract.^[40][41] The overall phenolic content has been measured (in an ethanolic extract) to be 195.4+/-3.6mg/g, with its antioxidant capacity 40% that of an equivalent concentration of Vitamin C and 20% that of pure gallic acid.^[32]

Hot water extracts have been noted to have 0.167% flavonoids, 0.134% coumarins, 1.672% total hydroxycinnamic acid derivatives, and 2.364% terpenoids.^[42]

Ethanolic extracts will confer more flavonoids than do the water extracts, although even when this happens the overall antioxidant effect is not greater than references (vitamin C and gallic acid) suggesting moderate to low antioxidant capacity; the hot water extract appears to have lower antioxidant potential.

Dandelion is known to accumulate heavy metals from the soil and can be used as a biomarker of mineral content of the soil, with copper concentrations increasing in a linear manner.^[39]

There is a formulation known as HV-P411 consisting of dandelion, schisandra chinensis, and Vitis vinifera (the plant of which grape seed extract comes from) which has been tested for its interactions with the liver.^[43][44]

While dandelion was not seen to upregulate many cytochrome levels (CYP2D, CYP3A, and total CYP) after four weeks dandelion tea ingestion (2% w/v), there was a reduction in the kinetic capacity of CYP1A2 to less than 25% of control, nonsignificantly greater than peppermint tea and chamomile at the same dose (green tea ineffective)^[45] while CYP2E was affected to a lesser degree (50% of control, similar to peppermint) and CYP2D and CYP3A were not affected by dandelion tea.^[45]

There is a potential concerning inhibition of CYP1A2 which may lead to some drug-drug interactions associated with dandelion extract, while two other common enzymes (CYP2D and CYP3A) appear to not be affected; more research is needed.

A tea solution of dandelion (2% w/v) failed to have any influence on hepatic glutathione S-transferase (GST) activity when given to rats over the course of four weeks, although the tea appeared to increase the activity of UDP-glucuronosyl transferase to 244% of control.^[45]

A large increase in one enzyme responsible for elimination of some drugs and supplements (those eliminated via glucuronidation) may mean a potential 'detoxifying' effect has basis. The antioxidant enzyme GST which is also involved in drug metabolism does not appear affected.

Although another species was used, dandelion (Taraxacum mongolicum) has been noted to reduce the bioavailability of the antibiotic drug known as ciprofloxacin when given a high oral dose (2g/kg) of the hot water extract, reducing both the max plasma concentration (by 73%) and the half life (from 5.71 hours to 1.96 hours).^[46]

One species of dandelion may interact with ciprofloxacin, it is not sure if this applies to the common species (officinale).

Dandelion has been used in a rat study using a forced swim test model of depression (alongside other behavioral tests), which noted that 50-200mg/kg of a hot water extract of the leaves had efficacy after two weeks of usage by reducing immobility time, whereas acute usage of 200mg/kg only was effective (acute usage of 50 and 100mg/kg ineffective) at the same thing;^[47] these effects appeared to be associated with decreased serum corticotrophin releasing factor (CRF) and corticosterone.^[47]

A single rat study indicates that dandelion extract in water may have antidepressant effects in mice. These results have not yet been replicated in humans or using other animal behavioral models of depression.

Dandelion has been found to have inhibitory actions on porcine pancreatic lipase with 250µg/mL of this extract inhibiting 86.3% lipase activity in vitro (IC₅₀ of 78.2µg/mL), which was comparable to Orlistat at the same concentration, although Orlistat had a much more potent IC₅₀ (0.22µg/mL).^[48] When 400mg/kg dandelion extract was fed to mice alongside fatty acids, the area under the curve (AUC, representing the total bodily exposure to a substance) of absorbed fatty acids over the next four hours was reduced by 23%.^[48]

A rat study suggests that dandelion extract, when co-ingested with fat, may reduce fat absorption, although it is less potent than the over-the-counter drug Orlistat.

Injections of dandelion hydroalcoholic extract (50-200mg/kg) in mice for 20 days noted that the two higher tested doses (100-200mg/kg) were able to mildly increase red blood cell (RBC) count and mean hemoglobin concentrations relative to control.^[49]

Injections of dandelion hydroalcoholic extract (50-200mg/kg) in mice for 20 days noted that all doses were equipotent at reducing platelet concentrations by approximately 10% (data derived from graph).^[49]

Dandelion root and leaf extracts have once shown cholesterol reducing properties when given as 1% (w/w) of the diet to rabbits fed a high-cholesterol diet; both the root and leaf extracts reduced triglyceride levels, while only the leaf extract raised healthy HDL levels while lowering unhealthy LDL levels (the root had no effect on HDL level and actually raised LDL levels further).^[50]

One rabbit study indicates that dandelion leaf extract may benefit lipid levels in animals fed a high-cholesterol diet.

Hot water extracts of dandelion have been noted to have minor inhibitory actions towards α-glucosidase, an enzyme that increases absorption of glucose by cleaving it from disaccharides and starch, when tested in 3 sources of α-glucosidase in vitro: baker's yeast, rabbit liver, and rabbit intestines.^[51] Dandelion extract reduced activity to around 40-80% of control with IC₅₀ values of 2.3mg/mL, 3.5mg/mL, and 1.83mg/mL respectively, but was less potent than the extract from another tested herb, Myrutus communis, and is similar to stinging nettle in potency while underperforming all reference drugs (glimerid, gliclazide, and acarbose).^[51]

Hot water extract of dandelion inhibits α-glucosidase (which digests starch) in vitro, which may reduce absorption of carbohydrates. No studies have confirmed whether this would work in vivo, however.

Dandelion root extract was noted to hinder differentiation of 3T3-L1 preadipocytes in vitro by approximately 30% at a concentration of 300-600µg/mL (with no significant difference between concentrations), with a 20-30% reduction in triglyceride accumulation with root extract at 300-600µg/mL (no dose-dependent relationship) and a dose-dependent decrease with leaf extract up to resulting in a 65% reduction in triglyceride levels during differentiation.^[34] and an inhibitory effect during adipogenesis with the leaf appearing to be more effective than the root extract.^[34] Leaf and root extracts also decreased lipid droplet accumulation by approximately 20% at 600µg/mL.

Dandelion extract hinders fat cell differentiation and lipid and triglyceride accumulation in vitro, with leaf extract being more potent in the latter function. Whether this would lead to reduced fat mass in vivo has not yet been tested.

Dandelion extract at high concentrations in vitro (400-800µg/mL) increased glucose uptake in C2C12 myotubes secondary to AMP-activated protein kinase (AMPK) activation, a protein which senses the energy level of cells and whose activation may reduce fatty liver and glucose tolerance;^[52] although dandelion extract did this to a lower level than the reference drug rosiglitazone, a PPAR-γ agonist.^[33] An increase in AMPK phosphorylation was noted after 10 weeks ingestion of a dandelion enriched high fat diet in mice (0.2% w/w of the diet) with no further phosphorylation occurring at 0.5% w/w.^[33]

Dandelion extract has been seen to increase in glucose uptake in skeletal msucles in rodents over the course of ten weeks secondary to AMPK activation.

Dandelion water extract at 10 or 100mg/kg in young male mice for ten days caused a dose-dependent reduction in immobility time in a forced swim test (mouse model of both antifatigue^[53] and antidepressive^[54] effects) with the higher dose (100mg/kg) reaching a significant reduction of immobility time (164+/-7.8s) relative to control (215+/-0.7s) by 24%.^[6] This change was associated with reductions in creatine kinase (CK) and lactate dehydrogenase (LDH), which are correlated to fatigue and muscle damage, in serum as well as an increase in serum glucose, although those former two biomarkers were changed to a similar degree in both dandelion doses while glucose increased only at the higher dose by 14%.^[6] Another study using the forced swim test and hot water extracts of dandelion found almost dose-dependent benefits between 10-100mg/kg after six weeks administration alongside increases in serum glucose and reductions in serum triglycerides.^[55]

Due to the exclusive usage of the forced swim test in rats and potential antidepressant effects of dandelion shown via this test^[47] it cannot yet be assumed dandelion possesses ergogenic properties as opposed to antidepressant properties.

An antifatigue effect of dandelion has been noted in mice subject to a forced swim test, although the results may be confounded by that test also measuring antidepressant effects. Influence of supplementation on other parameters of endurance exercise (such as treadmill running, usually a better model for ergogenic aids) remain untested.

Taraxasterol, one of the major bioactive components of dandelion, has anti-inflammatory properties in vitro.^[56] Since the inflammatory cytokine IL-1β may play a role in the cartilage degradation seen in osteoarthritis,^[57] taraxasterol was studied in vitro to assess its effects on IL-1β-stimulated chondrocytes.

One in vitro study found that taraxasterol dose-dependently inhibited IL-1β-induced NF-κB activation in human chondrocytes at concentration of up to 10 μg/mL.^[58] It has been previously shown that IL-1β normally works through NF-κB in chondrocytes to upregulate inflammatory mediators such as COX-2 and various matrix metalloproteinases (MMPs) which degrade cartilage and may contribute to osteoarthritis.^[59][60] It was found that taraxasterol blocked this process and downregulated production of COX-2 and MMPs in human chondrocytes, suggesting that it could theoretically slow the progression of osteoarthritis.^[58] However, this hypothesis has yet to be confirmed in either animal or human studies.

Injections of 200mg/kg of the hydroalcoholic extract of dandelion in mice for 20 days has resulted in an increase in average white blood cell (WBC) count relative to control, with 50-100mg/kg not having a significant effect,^[49] while the percentage lymphocytes in all groups saw a small increase due to a slight decrease in neutrophil count.^[49]

In vitro, macrophages treated with dandelion extract at 1mg/mL appear to secrete more tumor necrosis factor-α (TNF-α) and interleukin-12p70 (IL-12p70) in response to treatment with IFN-γ when incubated for both one hour and 24 hours to a similar degree, although lower concentrations (10µg/mL and 100µg/mL) were ineffective.^[6] All concentrations increased NO production in macrophages stimulated with interferon-γ (IFN-γ) thought to be secondary to an induction of inducible nitric oxide synthase (iNOS).^[6]

IL-10 production from IFN-γ was also enhanced in vitro at 100µg/mL and 1mg/mL, and were promoted inherently (i.e. without IFN-γ) at the higher concentration.^[6]

Moderate to high concentrations of dandelion extract appear to have a costimulatory effect on macrophages when in the presence of a stimulatory agent (IFN-γ), suggesting a possible proimmunity effect.

Dandelion extracts have been noted to suppress lipopolysaccharide (LPS)-induced inflammation when tested in vitro in macrophages, with a methanolic extract being more potent (IC₅₀ of 79.9µg/mL) than a water extract (157.6µg/mL), and with both leading to a reduction in lipid peroxidation and inflammatory signalling (iNOS induction and NF-kB activation) being noted.^[30] Benefits have been replicated elsewhere with leaf extracts where a chloroform extract showed the most efficacy in hindering nitric oxide production (more than an n-butanolic extract, which has been shown to be best in another study which did not assess chloroform extracts^[61]), IL-6, and PGE₂ formation at 62.5µg/mL while a water extract was ineffective at all doses up to 250µg/mL in this study.^[62]

The bioactive taraxasterol, which can be isolated from dandelion, appears to suppress the inflammation response of macrophages, with incubation of macrophages with 2.5-12.5μg/mL prior to LPS introduction suppressing iNOS and COX2 expression relative to LPS control.^[16] Polysaccharides isolated from dandelion have had similar effects when tested in isolation, suggesting that multiple compounds from dandelion may be antiinflammatory.^[23] While minor constituents, both luteolin and chicoric acid found in dandelion are bioactive on their own^[35][30] but have been noted to have synergistic properties in inhibiting macrophage stimulation,^[63] and thus may also contribute to dandelion's antiinflammatory properties. The higher levels of chicoric acid and luteolin in the methanolic extract of dandelion may explain its higher potency relative to the water extract.^[30]

With regard to LPS stimulation of macrophages, which is a commonly used assessment for inflammation, various components in dandelion appear to have a suppressive (antiinflammatory) effect.

In neutrophils activated by the ion-carrier A23187, the methanolic extract from the root of dandelion has been noted to have 90% inhibitory action (with respect to leukotriene B₄ formation) at a concentration of 3µg/mL, thought to be due to the sesquiterpene lactone content.^[14]

One study noted relatively potent suppression of neutrophils in vitro.

Taraxasterol isolated from dandelion was seen to have antiallergic properties in ovalbumin (OVA)-sensitized mice when given for five days at oral doses of 5-10mg/kg (with 2.5mg/kg being ineffective), with 10mg/kg being as effective in reducing white blood cell content in bronchoalveolar lavage fluid as the reference drug (2mg/kg dexamethasone) and was associated with less OVA-specific IgE production.^[64]

Dandelion extract itself has shown antiinflammatory properties in a mouse model of lung damage at a similar oral dose (2.5-10mg/kg) associated with reduced white blood cell (neutrophil) infiltration and production of inflammatory cytokines.^[65] This result has been replicated by pure taraxasterol at the same dosage range with a potency comparable to 5mg/kg dexamethasone.^[66]

There appear to be some protective antiinflammatory effects in the lung of mice seen with both taraxasterol and low levels of dandelion ingestion. This potential benefit requires human testing to confirm a role for dandelion in allergic conditions.

Dandelion hot water extract in peripheral mononuclear blood cells (PMBCs) infected with HIV-1 was able to inhibit viral replication with an IC₅₀ of 640µg/mL, reaching maximum efficacy (98%) at 2mg/mL, and showed more potent inhibitory action (IC₅₀ 230µg/mL) against another unrelated retrovirus (10A1-pseudotyped hybrid-MoMuLV/MoMuSV); the reference of AZT had an IC₅₀ of 0.29µM on HIV-1.^[40] The inhibitory effect was not thought to be related to the chlorogenic acid or caffeic acid content of the extract, since another tested herb with higher quantities of both (Artemisiae scopariae) had less potent inhibitory action.^[40]

Dandelion hot water extract has also been noted to possess anti-influenza properties with an IC₅₀ of 990µg/mL and full inhibition occuring at 5mg/mL, which was significantly weaker than the reference drug Oseltamivir (which exhibited full inhibition at 75µg/mL).^[41]

Dandelion shows antiviral properties against HIV and influenza in vitro, but it is significantly weaker than the reference drugs AZT and Oseltamivir, respectively.

While dandelion extract is traditionally used in Jordan as a fertility enhancer, oral ingestion of high doses of dandelion hot water extract (1.065g/kg and 2.13g/kg, a twenthieth and a tenth of the LD50, respectively) for sixty days in male rats appears to actually reduce serum testosterone concentration, secondary to testicular damage.^[42]

A high dose (approaching one-tenth of that needed to kill 50 percent of a poplulation of rats) of dandelion has been seen to induce fertility problems in male rats and lower serum testosterone; lower doses (which are normally recommended for supplementation) have not been tested.

Since dandelion has been traditionally used to treat abnominal distension, dyspepsia, nausea, and vomiting,^[3] its effect on the stomach has been investigated.

Dandelion ethanolic extracts have been noted to have a promotility effect on the stomach (increase in gastric emptying rate) when ingested at up to 100mg/kg in rats (EC₅₀ of 20.1+/-2.2mg/kg, maximal efficacy in the 50-100 mg/kg range) with a potency comparable to 2mg/kg cisapride as reference; this effect seemed to mediated through cholinergic stimulation (since blockade of the cholinergic, but not adrenergic, system had an effect).^[67]

One study noted that dandelion ethanolic extract increased stomach motility in rats.

The leaves and roots of dandelion at 200-600mg/kg appears to confer protective effects in the liver in mouse models of hepatotoxicity from CCl₄^[68][11][69] and acetominophen^[70] secondary to its antioxidant properties, as both of these drugs exert hepatotoxicity via oxidative means.^{[68][11][69][70]} n-hexane extracts are less protective at the same dose which may be due to their lower polyphenolic content compared to ethanolic extracts.^[68] Polysaccharides from dandelion (designated TOP1 and TOP2) may also have protective effects against CCl₄ at oral doses reflecting around 800mg/kg of a hot water extract in rats.^[22] Protective effects have also been noted with a hot water extract at a higher oral dose (1g/kg bodyweight in mice) against alcohol toxicity.^[71]

Intake of dandelion extract to mice on a high-fat diet (extract dose of 2g/kg or 5g/kg of the diet) for 10 weeks appeared to attenuate the production of fatty liver and hepatic inflammation and subsequent insulin resistance to a degree, with no significant differences between doses.^[33] these doses appeared to be sufficient to increase AMP protein kinase (AMPK) signalling in liver tissue.^[33]

Oral ingestion of dandelion at doses comparable to what a human would consume (around 10 grams for a 150lb person) appear to confer some minor protective effects in the liver according to rodent studies; human studies are currently unavailable. The mechanism seems to be due to through dandelion extract's antioxidant properties.

Dandelion hot water extract given orrally at a dose of 10mg/kg following administration of cholecystokinin to induce pancreatitis noted that production of inflammatory cytokines IL-6 and TNF-α was reduced relative to control.^[72]

Low doses of dandelion have shown minor protective effects in the pancreas in a rat model of pancreatitis, although no human studies are available.

Dandelion is traditionally used in Chinese and Ayurvedic medicine as a diuretic, a use which led to its name in French being pissenlit to reflect this property.^[38] In rodent models, the leaf appears to confer more diuretic potential than does the root^[73] with 2 grams of the leaf per kilogram bodyweight in mice (estimated human equivalent of 160mg/kg^[74]) having potency comparable to 80mg/kg furosemide,^[73] while elsewhere it was found that, in assessing fractions of dandelion extract, only the petroleum ether extract and the methanolic fractions had efficacy which was significantly lesser than 37.5mg/kg furosemide (dandelion dose based on dry weight not disclosed).^[37] It was hypothesized that this diuretic effect is due to the high potassium content in the leaves (4.51%) relative to the low sodium content (0.33% dry weight).^[37]

Oral ingestion of a dandelion extract (95% ethanolic extract) equalling about 8g of the fresh plant weight taken three times a day in otherwise healthy subjects was able to increase frequency of urination and overall urine output relative to the day prior to supplementation and the day after (urine output normalized after the third dose in the evening).^[38]

The diuretic role of dandelion is currently understudied. While a high potassium content is a probable explanation for a diuretic effect, other components of the extract have not been ruled out. The exact potency of this effect is not known, and while it does appear to work in humans the evidence is very preliminary.

MCF-7 breast cancer cells appear to experience less growth when in the presence of dandelion leaf water extracts, a property not observed with root or flower extracts;^[75] this growth inhibition was dependent on reducing signalling via ERK.^[75]

In HepG2 hepatoma cells treated with dandelion extract (8% water extract) at 200-2,000µg/mL for 24-48 hours (with 20µg/mL being ineffective), the extract appeared to reduce viability to 80% of control and increased apoptosis rates, with 200µg/mL increasing apoptosis by 28.7% (24 hours) and 38.8% (48 hours);^[76] this increased apoptosis was associated with more tumor necrosis factor alpha (TNF-α) and IL-1α secretion from hepatocytes, which were confirmed to contribute to the observed apoptosis since antibodies against these cytokines blocked the effects.^[76]

Dandelion (root) hot water extract has been noted in vitro to have anticancer properties at the level of the pancreatic cancer cell (BxPC-2 and PANC-1) by inducing autophagy secondary to loss of mitochondrial membrane potential; the same concentration of extract did not appear to have this function in noncancerous fibroblasts.^[77]

One study has found that the hot water extract of dandelion leaves, but not roots nor flowers, reduced the invasiveness of LNCaP prostatic cancer cells associated with less secretion of the matrix metalloproteinases MMP2 and MMP9, which help digest the surroundings of the tumor and may lead to metastasis.^[75]

Despite dandelion's use in the country of Jordan as a fertility enhancers, the hot water extract of dandelion given at two doses (1.065 and 2.13g/kg) to male rats over the course of sixty days in fact reduced fertility (from a reference 100% in control to 55.5-66.6%) associated with reduced sperm count and impaired sperm morphology.^[42] Serum testosterone appeared to also be reduced in accordance with abnormalities in testicular histology.^[42]

The above dose did not appear to have any overt teratogenic effects, and the estimated vegetable equivalent for this dose (see toxicology section for calculations) is 7.7g/kg fresh weight of dandelion.^[42]

Higher than normal doses of dandelion extract impair male fertility in rats due to testicular damage; the effect of recommended doses is not known.

When looking at the hot water extract, studies using doses claimed to be one tenth (2.13g/kg) and one twentieth (1.065g/kg) the supposed oral LD₅₀ of 21.3g/kg in rats have found impairment to male fertility;^[42] the lower dose being around 2.5-5 times higher than the higher dosage used for antioxidant effects (400mg/kg of the hot water extract). Assuming no major interspecies differences, this translates into an estimated minimum toxic dose of around 170mg/kg in a human.^[74]

170mg/kg refers to the dry weight of the hot water extract, which is approximately 17% the weight of the plant's dry weight^[40][41] yeilding a minimum toxic dose of dry plant as 1g/kg. Assuming a water content of 87%^[38] the minimum weight of the actual plant to cause fertility issues in men would be 7.7g/kg bodyweight.

Other studies assessing the oral LD₅₀ have found no acute toxicitiy associated with 10g/kg where intraperitoneal injections of 4g/kg were tolerated in both rats and mice^[3] whereas in mice an LD₅₀ has been noted with intraperitoneal injection of 28.8g/kg of the herb and 36.8g/kg of the root.^[3]

The known LD₅₀ of dandelion in rodents appears to be much higher than a human can expect to consume even with excessive ingestion of the vegetable, although the lowest dose associated with side-effects (while still higher than the recommended dose) could potentially be consumed with a high dietary intake of dandelion or high usage of dandelion supplements.

Dandelion is a plant of which it is possible to be allergic to, and it is advised people avoid supplementation or ingestion if there is a known allergic to honey, chamomile, chrysanthemums, yarrow, feverfew, and with some caution extended to other allergenic plants of the Asteraceae family such as ragweed, sunflower, and daisies.^[3] The most common form of allergy from dandelion is contact dermatitis^[3] and patch tests are available for assessment.^[78]

It is possible to be allergic to dandelion in which case supplementation should be avoided at all costs, and there may be some cross-allergenicity with other herbs in the same plant family.

There is a case report of a women with a history of type II diabetes on insulin therapy who experienced hypoglycemia two weeks after using dandelion in the form of a salad, and while causation was not placed on dandelion there was no recurring hypoglycemia after dandelion ingestion ceased.^[79]