Dill

Anethum graveolens (of the family Apiaceae), commonly referred to as Dill and less commonly referred to as Lao coriander, is a sparse looking plant with feathery leaves and tiny yellow flowers growing in the Mediterranean region, Europe, central and southern Asia while also being cultivated in Iran.^[1] It is also referred to as 'Pakchee Lao' in Thai^[2] and despite not being a Traditional chinese medicine appears to have some usage in China.^[3] Interestingly, the medicinal component of this plant appears to mostly be the fruits.^[4]

Traditional usage of anethum graveolens includes gastrointestinal ailments such as flatulence, indigestion, stomachache as well as for the purposes of a carminative, antispasmodic, sedative, galactagogue, diuretic, and antihyperlipidemic.^[5] Alongside the usage of being a galactogogue, anethum graveolens is also used for other feminine purposes such as uteral and cervical health as well as for cervical ectropion.^[3]

Dill (Anethum graveolens) is a food product that also appears to have some traditional medical usages for gastrointestinal health, urinary health, and feminine health related to lactation and menstruation

Anethum graveolens is known to contain (fruits unless otherwise specified):

• Dillanoside^[6]
• The psychotropics dillapiol and apiol^[7]
• Monoterpenoid ketodiols^[4] and glycosides^[4]
• Shashenoside I^[4]
• Syringin^[4]
• Icariside F2^[4]
• Nitrate (2,236-3,267mg/kg; average of 2,936mg/kg)^[8]
• Benzyl-β,D-glucopyranosides, 4-hydroxybenzyl-β,D-glucopyranosides, and 4-hydroxybenzyl alcohol 4-O,β,D-glucopyranosides^[4]
• Erythritol^[4]
• D-threitol^[4]
• β-carotene at 4039+/-266µg/100g in the leaves^[9]
• Lutein and Zeaxanthine (collectively at 4618+/-304µg/100g) in the leaves^[9]
• β-Cryptoxanthin at 61+/-7µg/100g (leaves)^[9]
• Uridine and thymidine^[4]

The bioactives of dill are not very well known at this moment in time, although it seems the essential oil component is fairly important and dill does have an appreciable nitrate content

While the essential oil fragment (found in seeds and fruits) contains:

• D-Carvone, reported to be near 50-60%^[4] but elsewhere quantified at 2.47% at the flowering stage (none prior)^[10]
• Dihydrocarvone (cis and trans)^[4]
• Carveol (cis and trans)^[4]
• L and D-Dihydrocarveol^[4]
• Carvacrol^[4]
• Limonene^[4] at 3.4-3.7% with one sample (flowering stage) at 10%^[10]
• α-terpinene and γ-terpinene^[4]
• β-Terpineol^[4]
• Terpinene-4-ol^[4]
• Terpinolene (0.06% or less)^[10]
• n-undecane (0.1-0.2%)^[10]
• α-Phellandrene^[4] at 26-47% and β-Phellandrene at 7-9%^[10]
• α-pinene at 1.8-2.6% and β-pinene at 0.1-0.3%^[10]
• p-cymene^[4] at 5-6.6%^[10]
• Thymol^[4] at 0.33-0.35%^[10]
• (3R, 4S, 8S)-3,9-epoxy-1-menthene (Dill ether, an odorant)^[11]
• Myristicin at 7.6% at initial growth phases, declining to trace levels at the flowering stages^[10] with Apiol (another psychotropic^[7]) initially at 4.3% and declining to 0.7%;^[10] Dillapiol is also present in the oil^[7]

The essential oil, found mostly in the fruits and seeds, it is either D-Carvone or Phellandrene isomers (likely higher in phellandrene since those things underlie the characteristic taste of dill). Although the following decline rapidly during plant growth, there appears to be a hallucinogenic/psychotropic component (Myristicin, Apiol, Dillapiol)

Dill has a phenolic content of 462.80+/-4.59mg GAE/100g and a flavonoid content of 10.90+/-0.11mg Quercetin equivalents/100g^[12] and appears to have a total carotenoid content of around 8.7mg/100g of the leaves;^[9] both being very small quantities relative to other herbs.

The seeds bear an essential oil content that is 3.5% of the seed weight^[3] and also appear to contain alkaloids (2.8+/-0.1%), flavonoids (11.05+/-0.07%), tannins (19.71+/-0.28%), and saponins (0.55+/-0.04%) with no apparent cardiac glycoside content^[13] which have been detected (qualitatively) before.^[14][15]

The fruits appear to have an essential oil content of 3-4%.^[4]

It has been noted that the volatile (S)-α-Phellandrene appears to be the characteristic odor, although the molecule (3r, 4S, 8S)-3,9-epoxy-1-menthene played a part in modifying the odorous properties.^[11]

The essential oil of anethum graveolens has been found to inhibit butyrylcholinesterase, with 200μg/mL with the n-hexane extract causing 46.58+/-4.77% inhibition and the dichloromethane extract inhibiting 47.92+/-5.52% of activity;^[16] there was no inhibition of acetylcholinesterase with any extract.^[16]

Possible inhibition of peripheral metabolism of acetylcholine, physiological relevance unknown

A 1:5 ratio of Cissampelos pareira:Anethum graveolens (50% ethanolic extract) at 2-50mg/kg oral intake for 14 days alongside a cholinergic toxin (AF64A) is able to protect rats from the impaired performance in a water maze test;^[12] the potency is comparable to the reference drugs of Donepezil (1mg/kg) and Vitamin C (250mg/kg) and no dose-dependence was noted.^[12]

The increase in acetylcholinesterase seen with the toxin was normalized with the two higher doses of the above mixture (10-50mg/kg) to a level comparable to 1mg/kg Donepezil.^[12]

Oral ingestion of 50-450mg/kg Anethum graveolens to rats for two weeks noted that the lowest dosage increased mounting frequency (to around three-fold) after a single dose, but continued dosing was progressively less effective and the higher doses were also less effective.^[2]

An odd interaction with libido, but the low oral dose and time required to experience an increase in libido enhancement may make for an interesting acute sexual aid

In persons with metabolic syndrome, daily supplementation of 600mg dill has failed to significantly reduce blood pressure.^[5]

A preliminary animal study using anethum graveolens leaves following the removal of a class of molecules (furanocoumarins) reported a reduction of triglycrides by 50% in rats and a similar potency was noted in the seeds (42%).^[17]

Subsequently, 650mg of dill twice daily in persons with high cholesterol for six weeks failed to improve triglycerides (actually causing a 6% nonsignificant increase)^[18] a failure which has been seen elsewhere with 600mg daily in persons with metabolic syndrome.^[5]

A study in animal suggested very potent triglyceride reducing effects of anethum graveolens, but subsequent human studies using standard supplemental dosages have twice failed

650mg of dill twice daily for six weeks in persons with high cholesterol failed to significantly benefit cholesterol, with nonsignificant changes in HDL-C (3.1% reduction), LDL-C (6.3% reduction), and total cholesterol (0.4% reduction).^[18] 600mg once daily in persons with metabolic syndrome has also failed absolutely when taken over three months.^[5]

Supplementation of 600mg dill daily for three months in persons with metabolic syndrome appears to be capable of reducing blood platelet (concentrations) after 12 weeks of supplementation, although there was no influence after eight weeks only.^[5]

In persons with metabolic syndrome, there is no significant influence of 600mg dill over three months relative to placebo.^[5]

The flowers of Anethum graveolens, at a concentraiton of 25-100µM in RAW 264.7 cells, caused a concentration-dependent reduction in macrophage activation in response to LPS which appears to be associated with NF-kB inhibition.^[19]

The water extract of dill appears to directly scavenge radicals in a DPPH assay by 79.66% at a concentration of 1,000μg/mL, it also shows reducing potential of H₂O₂ with less potency coming from the ethanolic and acetone extracts.^[20] Elsewhere, the water and alcoholic extracts were equipotent at reducing lipid peroxidation in vitro^[21] and the acetone extract has equipotent (to the water extract) in its antioxidative properties.^[22] Regardless of the extract used, all components of dill are significantly less effective than the references of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT).^[23]

The water extract can chelate metals by 60% in vitro at a concentration of 400μg/mL^[23] which was more effective than the ethanolic or acetone extracts although all were significantly less potent than the reference of EDTA.^[23]

Possessses both mineral chelating properties as well as antioxidative properties, but in vitro data suggests that it is significantly less potent than the reference drugs

In mice subject to pylorus-ligated stomach ulceration, the seeds of anethum graveolens (water and ethanolic extracts) appear to reduce stomach acid with a potency comparable to 32mg/kg cimetidine (reference drug).^[24] The water and ethanolic extracts were somewhat comparable in potency, requiring 70-170mg/kg to reach the EC₅₀ value and seemed to be active following injections as well.^[24]

Oral ingestion of the seeds also exert protective effects against alcohol induced ulcers (EC₅₀ values of 340g/kg for the water extract and 1.73g/kg for the ethanolic extract) and against HCl induced ulcers (EC₅₀ values of 120mg/kg for the water extract and 1.12g/kg for the ethanolic extract); a potency comparable to sucralfate (100mg/kg) as the reference drug.^[24]

The seeds of anethum graveolens appear to be able to reduce stomach acidity and may protect the stomach against ulceration

The fruits of anethum graveolens have been noted to have diuretic properties in dogs associated with increased urinary Na⁺ and Cl^- concentrations.^[14]

Appears to have diuretic properties

Oral ingestion of 50-450mg/kg of dill to rats for up to 14 days has failed to alter testicular weight, histology, and seminal parameters; there was some indication that some proteins were phosphorylated after a single day of the lowest dose (50mg/kg) but these were not specified.^[2]

High doses of dill have been reported (case studies, dosage not specified) to reduce libido and impair spermatogenesis.^[25]

Anethum graveolens extracts up to the highest tolerable doses (450mg/kg ethanolic extract or 5g/kg for water) appears to have anti-fertility effects in male rats (prolonging the time required to impregnant females) when taken daily for 42 days without altering serum testosterone nor damaging sperm cell morphology;^[26] the pups born to the fathers were not damaged in any visible way^[26] and this anti-fertility effect has been noted with 70-100mg/kg of the water extract in rats elsewhere where there was no apparent DNA damage to spermatids.^[27]

Via histological examination, it appeared that sperm cells clustered closer and more numerously in the seminiferous tubules which narrowed their diameter slightly.^[26] It is thought that dill modifies adhesion factors on the sperm and interferes with sperm-egg interactions.

Dill appears to be an anti-fertility drug for males, but at the doses which it is effect it does not appear to reduce serum testosterone nor does it possess toxic effects on the sperm cells or testicles

Dill has been claimed to promote mensturation,^[28] which is a traditional claim usually associated with abortifacient compounds; due to this, the interactions of dill and pregnancy have been explored.

Extracts of dill up to 5g/kg (or in the case of ethanolic, 0.45g/kg; all of which are the highest nontoxic doses^[24]) have failed to alter reproductive organ weight in female rats.^[25] There were no alterations in serum progesterone, although the chloroform extract reduced estrogen somewhat and prolonged pregnancy (no birth defects resulted).^[25]

Dill appears to interact with pregnancy, but currently there are no known toxic effects to the fetus or abortions induced from the supplement; the topic requires more research

Dill is claimed to be a galactogogue.^[28]

In mice, injections of the water extract of the seeds appear to have a maximal tolerable level of 450mg/kg whereas ethanolic extracts are safe up to 5,000mg/kg;^[24] the LD₅₀ values for injections of the ethanolic seed extract and water extracts are 3.04g/kg and 6.98g/kg respectively.^[24]

The hydroalcoholic extract of dill appears to possess a NOAEL of 50mg/kg in mice when injected over the course of 45 days, which was due to a decrease in white blood cell count seen with 500-1,000mg/kg;^[29] acutely, doses of up to 2,000mg/kg were nontoxic.^[29]

While the recommended dose of Dill for what is used as a supplement is safe, there is toxicity associated with higher levels of dill and the dosage where toxic effects are seen is low enough to feasibly be overconsumed via food

Contact dermatitis^[30] and urticaria^[31] to dill have both been reported, suggesting the possibility of topical allergies. In skin prick testing dill has shown cross-reactivity with fennel, coriander, caraway, and aniseed.^[32]