Milk Thistle

The extract of the milk thistle plant, silymarin, or its major flavonolignan silibinin, can act to supplement sunscreen protection in skin care formulations due to its strong photoprotective effect. Silymarin also appears capable of lightening the skin.


Grade Level of Evidence
A Multiple double-blind, controlled clinical trials.
B 1 double-blind, controlled clinical trial.
C At least 1 controlled or comparative clinical trial.
D Uncontrolled, observational, animal or in-vitro studies only.
Grade Effect Size of Effect Comments




Works via both a sunscreen effect and multiple mechanisms at the cellular and molecular level to suppress sunburn, DNA damage and photocarcinogenesis.




Scavenges free radicals and can oppose the induction of oxidative stress and damage caused by UV radiation.


Skin lightening


Reduces melanin production by inhibiting the expression of tyrosinase, the enzyme that catalyzes the rate-limiting reaction of melanogenesis.




Speeds up wound healing through its antioxidant and anti-inflammatory effects, as well as by upregulating the production of collagen and glycosaminoglycans.

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Table of contents:

1. Sources

The milk thistle plant Silybum marianum is a flowering herb native to the Mediterranean region that is now widespread throughout the world.[1] The extract of its seeds, termed silymarin, has been used as a traditional herbal remedy for nearly 2000 years[2] and is well-known for its hepatoprotective action.[3]

Silymarin is a complex of at least 7 flavonolignans (silybin, silydianin and silychristin) and 1 flavonoid (taxifolin) that together comprise 65-80% of milk thistle extract, with the remaining being fatty acids and polyphenolic compounds. The most abundant component in silymarin is silibinin, a 1:1 mixture of the diastereoisomers silybin A and silybin B[4] that makes up 50-70% of silymarin.[5]

One commonly cited dietary supplement of milk thistle extract used in clinical trials is Legalon or Thisilyn, a standardized preparation of approximately 80% silymarin or 32% silibinin by weight.[4]

2. Bioavailability

2.1 Oral administration

The oral bioavailability of silymarin is quite low owing to its poor solubility in water,[6] poor permeability and its degradation in the gastrointestinal tract.[7] In rats, the oral bioavailability of silibinin, the major component of silymarin, has been estimated to be just 0.73%.[8]

Methods that have been employed to augment the oral bioavailability of silymarin include complexation with phospholipids,[9][10][7] encapsulation in liposomes,[11] complexation with β-cyclodextrins,[12][13] incorporation in solid dispersions[14][15] and incorporation in nanocarriers such as nanoemulsions, solid lipid nanoparticles or polymeric micelles.[16][17][18]

Silibinin has a good tissue distribution profile and is found in the liver, lung, stomach, prostate and pancreas of mice after oral administration. It is also distributed to the skin, where peak levels are achieved 1 hour after administration.[19]

2.2 Topical administration

The flavonolignans silibinin, silydianin and silychristin in silymarin are all readily absorbed by intact mouse skin in both in vitro and in vivo experiments. Although all 3 compounds have the same molecular weight of 482.4 daltons, silibinin has the highest absorption due to its greater lipophilicity and its planar strucutre. Silychristin which has an additional hydroxyl group that makes it more hydrophilic, whereas silydianin has a cyclic ketone moiety that forms a steric bridge and increases its molecular volume, hindering skin penetration.[20]

The pH of the formulation wields a significant influence over the skin permeation and deposition of silibinin. The non-ionic form predominates at pH values lower than 6.86, the first acid dissociation constant of silibinin at 37°C. This is beneficial because the non-ionic form is more lipophilic, which enables higher skin partitioning of silibinin into the similarly lipophilic stratum corneum. Hence, the stratum corneum is the most important permeation barrier for the ionic form of silibinin, whereas the viable epidermis and dermis is a more important barrier when silibinin is in its non-ionic form.[20]

In one study, oil-in-water microemulsions containing 2% silymarin were not able to appreciably penetrate the abdominal skin of newborn pigs.[21] Another study showed that complexation of water-in-oil emulsions of milk thistle extract with hydroxypropyl-β-cyclodextrin increased its absorption by in vivo human skin from 30% to 80%, but did not lead to transdermal penetration.[22]

3. Effects on the skin

3.1 Antioxidant effect

Silymarin is a free radical scavenger that can oppose skin aging through its radical-inhibiting activity when included in topical formulations at a concentration of 0.1-0.5%.[23][24] Pre-treatment of silymarin to mouse skin and human keratinocytes have been shown to suppress oxidative stress and damage induced by UV light through inhibiting the production of reactive oxygen species.[25][26][27] In mice, this appears to be achieved by decreasing the infiltration of CD11b+ cells, which were identified as the major source of oxidative stress in UV-irradiated skin.[25][26]

However, another study found that silibinin, the main flavonolignan in silymarin, can elevate the production of reactive oxygen species and lead to enhanced apoptosis in human keratinocytes exposed to UVA radiation.[28] Based on these findings, it has been hypothesized that silibinin may be able to sense the extent of cell damage caused by UV irradiation, protecting the cell if the damage is moderate and promoting cell death if it is severe.[29]

3.2 Photoprotection

Silymarin has photoprotective properties. When incorporated in oil-in-water creams at a concentration of 10%, it gives an SPF similar to that of the sunscreen octinoxate.[30] In addition to this sunscreen effect, silymarin also works on a molecular level, as evidenced by numerous studies in different cell lines and animal models.

Both dietary and topical administration of silybinin strongly protect against sunburn cell formation.[31][32] Silibinin also protects against UV-induced epidermal hyperplasia, which is linked to the formation of actinic keratoses,[33][34][35][32] and reduces the amount of DNA damage caused by UV light by accelerating the repair of cyclobutane pyrimidine dimers.[36][37][38] The repair of DNA damage in dendritic cells by silymarin in turn contributes to its inhibition of UV-induced local immunosuppression,[39][25][40] Silibinin also has the ability to protect or enhance apoptosis depending on the dose of UV radiation administered, indicating that it may function as a damage sensor to exert its biological action.[41]

In an in vivo experiment performed on 24 rabbits exposed to strong sunlight for 3 hours/day for 30 days, rabbits treated with silymarin creams prior to exposure developed no clinical features, whereas those which did not receive treatment or which received the placebo, which developed high levels of dermal scaling, skin irregularity, erythema, hyperpigmentation and edema. Histopathological examinations confirmed these results, finding epidermal hyperpigmentation, hyperkeratosis, edema, inflitration of lymphocytes, plasma cells and eosinophils as well as squamous cell proliferation and increases in dermal thickness in all and more than half of the rabbits that had not been treated or had been treated only with the placebo, respectively. None of these microscopic changes were seen in the rabbits that received treatment with the silymarin creams,[42] suggesting that the topical silymarin applications prevented skin damage caused by solar radiation.

Together, these mechanisms help account for the observed anti-carcinogenic effect of silymarin. Topical silymarin applied before UV exposure markedly reduced tumour incidence, tumour multiplicity and tumour volume per mouse. The effect was pronounced in all stages of photocarcinogenesis, including tumour initiation, tumour promotion and complete carcinogenesis protocols.[43] Silibinin alone, too, has been demonstrated to inhibit tumour incidence, multiplicity and volume when applied before or immediately after UV exposure, or when administered through the diet.[35]

3.3. Lightening effect

Silymarin may have potential as a skin-lightening agent. It significantly inhibited melanin production in a dose-dependent manner in a mouse melanocyte cell line, apparently by inhibiting the expression of tyrosinase, the rate-limiting enzyme in melanogenesis. The inhibition is thought to be due to the suppression of prostaglandin E2 production, but further studies are required to fully elucidate silymarin's depigmenting mechanism.[44]

3.4 Melasma treatment

A double-blind, randomized clinical study was conducted on 96 melasma patients to assess the efficacy of 0.7% and 1.4% silymarin creams in vivo. After 4 weeks of twice daily treatment, all patients who had used either silymarin cream recorded excellent improvements, with an average melasma area and severity (MASI) score of 0, indicating complete clearance. Patients in the placebo group by contrast did no witness any improvement from baseline in their MASI scores, a difference that was statistically significant in favour of the silymarin treatments.[42]

3.5 Rosacea treatment

A topical treatment based on silymarin and methylsulfonilmethane (S-MSM) led to statistically significant improvements in skin redness, number of papules and itch intensity in a double-blind, placebo-controlled study of 46 patients, leading to the conclusion that this combination can be useful in managing rosacea skin, especially in the rosacea subtype 1 erythemato-telangiectactic phase.[45]

3.6 Improved healing

Silymarin is known to protect against oxidative skin injury induced by burns in rats.[46] It also enhances wound healing in rats, with the extent of improvement seemingly dependent on the dose. One experiment found that 4.5-6 mg of silymarin applied to rats with excision wounds increased epithelialization and decreased inflammation but did not affect wound contraction, collagenization or hydroxyproline levels.[47] However, in another study both 6 and 12 mg of silymarin significantly increased the amount of glycosaminoglycans and collagen in rats with full-thickness cutaneous wounds, ultimately improving the tensile strength of the healing tissue.[48] These results have been replicated in a third study that used 10% and 20% silibinin extracts.[49]

Significantly, there is some evidence that these findings can be extended to human cells, as pre-treatment of human fibroblasts with silymarin has been shown to confer protection against hydrogen peroxide-induced injury and to inhibit lipopolysaccharide-induced COX-2 mRNA expression. Its antioxidant and anti-inflammatory effects mean that silymarin may be useful for the therapeutic treatment of cutaneous wounds.[50]

3.7 Anti-dermatitis effect

Silymarin inhibited chemical-induced irritant contact dermatitis as well as atopic-like dermatitis caused by dust mite extract in mice.[51][52] A silymarin-based cream called Leviaderm was also found to be promising for preventing radiodermatitis caused by postsurgical radiotherapy in breast cancer patients, since it prolonged the median time to toxicity considerably and greatly reduced the proportion of patients that developed acute skin lesions, compared to the current standard of care.[53]

4. Side Effects

Long-term consumption of milk thistle extract by rats and mice resulted in significant reductions in body weights but did not affect survival. Interestingly, there was a negative trend in the incidence of mammary gland tumours in female rats that were exposed to 25,000 or 50,000 ppm of milk thistle in the feed, and similarly for liver tumours in male mice.[54]

Topical application of silibinin, silydianin and silychristin did not irritate the skin of nude mice as measured by changes in transepidermal water loss and erythema.[20] Furthermore, 140 mg of silymarin thrice daily did not cause any adverse events in 105 hepatitis patients treated for more than 2 years, validating the findings of a shorter study in which oral doses up to 2.1 g/day were well-tolerated.[55][56] Melasma patients who applied topical silymarin creams for 4 weeks did not experience any local or systemic adverse events either.[42]

Scientific References

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