Soy

Soy extract from the legume Glycine max contains many bioactive compounds including isoflavones and enzyme inhibitors. This gives it the ability to improve the properties of the skin, especially in postmenopausal women, and enables it to protect the skin from photodamage.

Effects


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

B

Wrinkle treatment

Strong

Stimulates the production of type I procollagen and inhibits the expression of collagen-degrading enzymes. An active soy formulation improved facial fine lines by 30% over 12 weeks.

B

Skin lightening

Moderate

Improves mottled pigmentation, lentigines, blotchiness and dullness of the skin.

B

Smoother skin

Mild

Soy moisturizers applied to the skin for 12 weeks decreased skin roughness in 2 separate clinical trials.

C

Increased skin thickness

Moderate

Reverses the thinning of the skin observed in postmenopausal women.

D

Increased skin hydration

Moderate

May hydrate the skin through stimulating the production of hyaluronic acid.

D

Photoprotection

Moderate

Suppresses UV-induced oxidative stress, DNA damage, photocarcinogensis, sunburn cell formation and erythema.

D

Antioxidant

Moderate

Quenches reactive oxygen species such as hydrogen peroxide, and inhibits lipid peroxidation.

D

Increased skin elasticity

Mild

Restores skin elasticity by inducing the activity of the elastin promoter and by protecting elastic fibers from degradation.

D

Reduced hair growth

Mild

Delays hair growth and reduces the size of hair shafts and hair follicles.

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Scientific Research


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Table of contents:

1. Sources

Soybeans contain many components with biological activity in the skin. Soy is composed mainly of phospholipids (45-60%) and essential fatty oils (30-35%). It is the minor components however that include the most active compounds, such as isoflavones and protease inhibitors.[1]

Isoflavones are phytoestrogens, plant-derived compounds with estrogenic activity.[2] In soybeans, they are bound to sugar molecules and hence present as the glycosides genistin, daidzin, and glycitin. Fermentation of digestion of soybeans releases the sugar molecules, leaving the isoflavone aglycones genistein, daidzein, and glycitein. It is these aglycones, particularly genistein and daidzein, that have been the most studied for their beneficial effects on the skin.

Soybeans also contain the protease inhibitors soybean trypsin inhibitor (STI) and Bowman-Birk inhibitor (BBI),[1] which have been studied for their effects on skin depigmenting.[3]

2. Bioavailability

Most studies have focused on the topical delivery of genistein and daidzein -- we were not able to find any published reports on the delivery of soy extract in general or that of its other components.

Like most polyphenols, the intradermal delivery of isoflavones is inefficient, due to their low skin permeability and low solubility in both aqueous and organic media.[4] For instance, genistein does not penetrate significantly through the stratum corneum after a single application.[5] Systems have therefore been developed to enhance their delivery.

The use of penetration enhancers,[6] liposomes,[5] micoremulsions,[4] nanoemulsions[7][8][9] and nanocapsules,[10] have all been demonstrated to increase the permeation of genistein and/or daidzein into the skin. A transdermal patch for the administration of soy isoflavones has also been patented.[11]

pH also affects the stability and absorption of soy isoflavones. Genistein is highly stable under neutral and oxidative conditions, but degrades under acidic and basic conditions.[6] Moreover, the skin deposition of the isoflavones is greater at pH 6, when the isoflavones are in a non-ionized form, that at pH 10.8, when they are ionized,[12] due to the lipophilic nature of the stratum corneum.

After penetrating the stratum corneum, genistein and daidzein permeate into the deeper skin layers. In one study, the amount of genistein retained in the stratum corneum did not fluctuate over time, but increasing amounts of genistein were found in the remaining skin.[13] Another study on pig skin showed that after 8 hours, the highest amount of genistein was retained in the epidermis, followed by the dermis, then the stratum corneum.[9]

Genistein and daidzein also appear to penetrate through the skin. Following transdermal application on ex vivo human skin, genistein and daidzein were found in the plasma,[14] with the concentration of genistein 3-fold higher than that of daidzein.[15] This may be due in part to more rapid removal of daidzein, as the urinary excretion of daidzein was also found to be 2-3 times higher that that of genistein. Repeated transdermal application seems to improve retention, with both plasma concentration and excretion rate declining markedly after a second application.[15]

3. Effects on the skin

Several studies have shown that topical soy extract improves photoaged skin. The earliest studies investigated the effects of an extract obtained by fermenting soy milk with Bifidobacterium breve. This extract restored the decrease in skin elasticity, increased skin viscoelasticity, hydrated and thickened the skin of hairless mice. When a gel formulation containing 10% of this extract was applied to the forearm of healthy volunteers for 3 months, it also slowed the decrease in skin elasticity.[16] These effects were thought to be related to the increase in hyaluronic acid production stimulated by genistein and daidzein, which were released from the glycosides during fermentation.[17]

Total soy preparations have demonstrated beneficial effects on photoaged skin. In 1 clinical study, a concentrated soy formulation with antioxidants significantly brightened and smoothed the skin of female participants, in addition to bringing about improvements in fine wrinkling, overall skin tone, skin texture, mottled hyperpigmentation and lentigines.[18] Similarly, a facial moisturizer containing a total soy preparation plus broad-spectrum sunscreens improved skin roughness, clarity, texture, softness and tone in a double-blinded and placebo-controlled trial.[19]

A commercially available soy moisturizer containing non-denatured STI and BBI (Aveeno Positively Radiant Skin Daily Moisturizer) has also been tested in a 12-week, double-blind and vehicle-controlled study involving 68 women. This product was statistically superior to the vehicle in improving mottled pigmentation, blotchiness, dullness, fine lines, texture, skin tone and overall appearance. In fact, the vast majority of the women achieved at least a 1-grade improvement in mottled hyperpigmentation (90%) and fine lines (87%). Furthermore, all of the women had decreased skin roughness, increased skin clarity, and almost all had improved skin tone.[20]

An assessment of topical depigmenting agents on the solar lentigines of Asian women also revealed that a stabilized soy extract had a better, though modest, lightening effect compared to a 20% azelaic acid formulation, as well as another formulation containing 5% ascorbyl glucosamine, 1% kojic acid and alpha-hydroxy acid esters, which were not effective.[21]

Soy has been purported to exhibit a few potential modes of action which may correlate with the topical treatment of photoaging.[1]

Hyaluronic acid is important for tissue repair and for maintaining skin hydration,[22] and its content has been proven to decline in aged skin.[23] The soy isoflavones genistein and daidzein enhanced the production of hyaluronic acid in transformed human keratinocytes and in hairless mouse skin,[24] though the exact mechanism by which this occurs is not known.

Moreover, soy extract and the isoflavones it contains are known to both stimulate the synthesis of type I procollagen[25] and inhibit the expression of matrix metalloproteinases, enzymes that degrade collagen, in skin fibroblasts.[26][27] Genistein, for instance regulates the expression of c-jun and c-fos, which in turn regulate the expression of collagenase, enzymes that break the peptide bonds in collagen.[28][29] Whole topical soy has been observed to stimulate collagen synthesis to a greater extent than purified isoflavones, suggesting that other ingredients in soy, too, may play important roles in collagen accumulation.[22]

In vitro studies have discovered that non-denatured soybean extracts also contribute to the resilience and elasticity of the skin by inducing elastin promoter activity, inhibiting elastase activity and protecting elastic fibres from degradation.[30] Topical treatment of human skin explants with non-denatued soybean extracts also revealed an enhanced elastic fiber network, resulting from the induced synthesis of tropoelastin, the elastin fiber monomer, and fibrillin-1, an elastin accessory protein.[31]

Topical application of an isoflavone-containing emulsion was shown to increase the number of dermal papillae after 2 weeks in a placebo-controlled, in vivo study.[22] This is significant, as the disappearance of dermal papillae and the flattening of the junction with the atrophic epidermis are among the most reproducible structural changes in aged skin.[32]

The depigmenting activity of soy extract is attributable to the serine protease inhibitors STI and BBI, which affect skin pigmentation by inhibiting protease-actived receptor-2 (PAR-2) mediated phagocytosis of melanosomes by keratinocytes.[3][33] Non-denatured soybean extracts may also contain additional active skin lightening agents, as they are superior to either STI or BBI alone in their depigmenting effect despite having much lower concentrations of STI and BBI.[31]

3.2 Improvements in postmenopausal skin

Decreased estrogen at menopause has been associated with deleterious skin changes including the breakdown of extracellular matrix proteins, skin thinning, reduced blood vessels, reduced skin elasticity and increased wrinkling.[34][35][36]

2 studies have been conducted to examine the effects of topical soy isoflavones on the skin of postmenopausal women. The first, a double-blind, estrogen-controlled trial, found that the isoflavones increased epidermal thickness by 20% and the number of blood vessels by 36%. The number of fibroblasts also rose significantly. However, the magnitude of these changes were markedly lower than that induced by topical administration of estradiol.[37]

The second study was a prospective, randomized, double-blind trial that compared the effectiveness of 4% genistein gel versus 0.01% estradiol gel on postmenopausal skin. Skin biopsies revealed that both treatments increased the concentration of hyaluronic acid, but again the effect was greater for estradiol than for genistein.[38]

It has been proposed that the ability of the isoflavones to activate estrogen receptor beta (ER-β) is responsible for their efficacy in protecting skin from aging, more so than their antioxidant properties.[39] If this is true, then it is understandable that soy isoflavones exert less protection against photoaging than estradiol, as the isoflavones are generally weak estrogen agonists compared to estradiol.[40][41]

3.3 Photoprotection

Soy extract provides photoprotective benefits to the skin via multiple mechanisms. Pre-treatment of animals with genistein significantly inhibited the series of oxidative events elicited by UVB irradiation, including the production of the reactive oxygen species hydrogen peroxide and lipid peroxidation.[42] An isoflavone extract from soybean cake also increased the activity of catalase and suppressed the expressions of COX-2 and PCNA, indicating that the anti-photoaging effect of soy extract is due at least in part to its anti-oxidative and anti-inflammatory actions.[43] One study noted that genistein liposomal gel demonstrated better anti-oxidative effect compared to genistein-suspended gel, as the incorporation of genistein in liposomes results in localization of the drug in the deeper skin layers.[44]

The antioxidant effect of soy extract relates to its capacity for protecting against UV-induced oxidative damage to DNA. In a study on human skin fibroblasts, a mixture of soy isoflavone glucosides and aglycones prevented 71% of UVB-induced DNA damage.[45] Together, genistein and daidzein also exert a synergistic photoprotective effect that is greater than the effect obtained with each isoflavone alone.[46]

Apart from inhibiting the formation of DNA lesions such as UVB-induced cyclobutane pyrimidine dimers[26][47] and 8-hydroxy-2'-deoxyguanosine,[48] soy isoflavones also affect the expression level of Gadd45, a protein involved in DNA repair.[46][45] This at least partly explains why treatment with an alcoholic solution of genistein and daidzein enhanced DNA damage repair by 34-35% after 4 hours.[49]

In addition, topical application of non-denatured soy milk, non-denatured soy extract, STI or BBI have also been reported to inhibit the formation and growth of UV-induced skin tumours.[50][51][52] It has also been suggested that non-denatured soy extracts may inhibit angiogenesis and thus tumour progression, due to its suppression of vascular endothelial growth-factor induced endothelial tube formation in Matrigel.[51] Meanwhile, geinstein is known to suppress the expression of the proto-oncogenes c-fos and c-jun, making it a potential preventative agent against photocarcinogenesis.[53]

In a study on pig skin, topical application of individual 0.5% solutions of genistein and daidzein protected against solar-simulated UV-induced photodamage, as measured by sunburn cell formation and erythema. The protection afforded was less than that provided by a topical combination antioxidant standard containing 15% ascorbic acid, 1% α-tocopherol and 0.5% ferulic acid, however.[54]

3.4 Reduced hair growth

Apart from their documented skin lightening effect, topical STI, BBI or soy milk also leads to delayed and reduced hair growth. In one study, hairs were visibly thinner, more directionally organized and smoother to touch, relative to untreated controls. Hair follicles also became smaller and less developed, with the diameters of the hair shaft and hair bulb reduced by 42% and 24%, respectively.[55]

4. Side Effects

The safety and tolerability profiles of topical soy extract, isoflavones and protease inhibitors are not well-characterized -- we are not aware of any published toxicity or safety assessments. However, few adverse events have been experienced in the human studies conducted so far. This is in line with the observation that topical application of soy isoflavones seem to cause no or negligible erythema or disruption of the stratum corneum.[12] Further, genistein, daidzein and glycetein inhibited tretinoin-induced epidermal hyperplasia in a human skin organ culture, suggesting that the use of soy extract or its constituent isoflavones may actually be a way of mitigating the unwanted epidermal effects of topical retinoid therapy.[25]

Scientific References


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