Eczema Treatment: Gene based Approaches 2023

In the following sections, we’ll outline gene-based approaches that may help you deal with eczema. Read on to find out what you can do to manage this condition.

The strategies below are not meant to replace your standard medical treatment. Make sure to consult with your doctor before making any significant changes to your day-to-day routine.

Image via www.merckmanuals.com

FLG & OVOL1

Probiotics

Treatment of a reconstructed human skin cell model with L. rhamnosus significantly increased the production of filaggrin. Similarly, L. plantarum supplements were found to increase filaggrin production in rat and mouse models of eczema [12].

In people with eczema, supplementation with different probiotic strains slightly improved skin inflammation. The most common Lactobacillus species tested include L. rhamnosusL.reuteriL. plantarumL. paracaseiL. fermentum, and L. sakei [34567879].

Bifidobacterium species such as B. animalisB. breve, and B. longum have been mainly tested in combination with Lactobacillus strains. The studies produced mixed results, possibly due to differences in the strains used [31011121314].

Preventive prenatal maternal or postnatal pediatric supplementation with combinations of some of these Lactobacillus and Bifidobacterium strains in families with a history of atopic disease significantly lowered the incidence of eczema in children [15164171819202021222324].

Borage Oil

Filaggrin was observed to increase in amount in guinea pigs fed borage oil [25].

Borage oil contains high levels of omega-6 fatty acids (such as gamma linolenic acid) that are vital to the proper structure and function of the skin barrier [26].

In a few studies of children with seborrheic dermatitis, topical borage oil improved the symptoms within 1-3 weeks [272829].

In children with eczema (atopic dermatitis), wearing undershirts coated with borage oil for 2 weeks improved their skin barriers. They also had relief from itch [30].

Coconut Oil

Virgin coconut oil increased the amount of filaggrin and decreased the amount of inflammatory proteins found in human cells. From these observations, the authors of the study suggested that virgin coconut oil may enhance the integrity of the skin barrier [31].

Virgin coconut oil, applied daily for eight weeks, was an effective treatment for mild to moderate atopic dermatitis (eczema) in a clinical trial [32].

Coconut oil has also been reported to moisturize the skin and prevent infections, which may further help improve eczema [3334].

TLR10

Sunlight Exposure/Vitamin D

Vitamin D treatment increased TLR10 levels, resulting in an anti-inflammatory response, in a study in cells of the uterine lining [35].

Studies have associated low blood vitamin D levels with eczema (atopic dermatitis) in children. In people with food sensitization, those with the lowest vitamin D levels had more severe eczema [36373839].

A healthy exposure to sunlight is the best way of increasing your blood vitamin D levels. In addition, you can eat food sources of this vitamin (such as fatty fish, liver, egg yolks, and dairy) [40].

Research also suggests that vitamin D supplementation can improve eczema severity, although some studies found it ineffective [37414243].

Probiotics

Different probiotic strains, such as L. acidophilus and L. paracasei, can enhance antimicrobial immunity through TLR activation [444546].

In people with eczema, supplementation with different probiotic strains slightly improved skin inflammation. The most common Lactobacillus species tested include L. rhamnosusL.reuteriL. plantarumL. paracaseiL. fermentum, and L. sakei [34567879].

Bifidobacterium species such as B. animalisB. breve, and B. longum have been mainly tested in combination with Lactobacillus strains. The studies produced mixed results, possibly due to differences in the strains used [31011121314].

Preventive prenatal maternal or postnatal pediatric supplementation with combinations of some of these Lactobacillus and Bifidobacterium strains in families with a history of atopic disease significantly lowered the incidence of eczema in children [15164171819202021222324].

IL2 & IL2RA

Sunlight Exposure/Vitamin D

Vitamin D stimulates IL-2, and they work together to increase the activity of Tregs and suppress inflammation [4748].

Studies have associated low blood vitamin D levels with eczema (atopic dermatitis) in children. In people with food sensitization, those with the lowest vitamin D levels had more severe eczema [36373839].

A healthy exposure to sunlight is the best way of increasing your blood vitamin D levels. In addition, you can eat food sources of this vitamin (such as fatty fish, liver, egg yolks, and dairy) [40].

Research also suggests that vitamin D supplementation can improve eczema severity, although some studies found it ineffective [37414243].

Acupuncture

In one study of patients with chronic allergic rhinitis, those who underwent acupuncture treatments had significantly altered IL-2 profiles compared to those who did not. However, the IL-2 levels of both the acupuncture group and the placebo group were, on average, within the normal ranges. This result suggests that acupuncture may work better for some people than others [49]

A meta-analysis of 8 studies found acupuncture effective at reducing the symptoms and severity of eczema. However, the authors warned that all the studies compared acupuncture with no treatment or with conventional medication instead of using a more suitable negative control (“sham” or fake acupuncture) [50].

Vitamin E

In multiple rodent studies, increased dietary vitamin E intake increased IL-2 production. The increase was most significant in older animals [5152].

In 3 clinical trials of people with eczema, supplementation with high doses of vitamin E improved the symptoms and quality of life [535354].

Milk Thistle

Silymarin from milk thistle prevented the suppression of IL-2 production in the skin of mice exposed to UV radiation [55].

Silymarin formulated into a cream prevented dermatitis from radiotherapy in 2 trials of breast cancer patients [5657].

Licorice

In mice with cancer, carbohydrates from licorice increased IL-2 levels [58].

A gel with 1-2% of licorice root reduced skin redness, itching, and swelling in people with eczema. A different herbal formulation with licorice root, willow bark, and gentian root extracts had anti-inflammatory effects comparable to those of hydrocortisone in another study [5960].

Similarly, formulations containing licorice’s active compound licochalcone A, applied on the face, forearms, and scalp, improved skin itching, inflammation, redness, and dryness as effectively as hydrocortisone [616263646566].

Cannabidiol (CBD)

Cannabidiol (CBD) can increase IL-2 production in T cells, which suppresses the immune response by stimulating the activation of Tregs [6768].

In a small trial on people with eczema and other skin conditions, an ointment containing CBD (without THC) improved the symptoms and skin parameters such as hydration, barrier function, and elasticity [69].

The anti-inflammatory effects of CBD in a cell-based study suggest it may also help with allergic dermatitis [70].

Echinacea

Echinacea extract increased IL-2 levels in a small clinical trial of healthy volunteers and a study in rats [7172].

In a small trial of people with eczema, applying a cream with echinacea for 3 months helped improve skin redness, swelling, and barrier function [73].

TSLP

Light Therapy

In mice with eczema, both the combination of low-dose LED light therapy with water baths and the irradiation of the eyes with ultraviolet A radiation improved eczema lesions, in part by reducing TSLP levels and the associated Th2 immune response [7475].

Ultraviolet (UV) radiation has been most extensively used for eczema, especially in severe cases. While UVA is more effective to improve flares (especially if combined with the photosensitizer psoralen), UVB is preferable to manage chronic eczema. Importantly, UVB is less likely than UVA to cause skin cancer [76777879].

UV radiation helps with eczema by inhibiting inflammation and the immune response, making the skin thicker, and killing potentially infectious skin bacteria [808182].

Blue light therapy helped reduce disease severity, itching, and number of lesions in 2 trials on people with eczema. In one of them, blue light was shown to reduce T cell activation and cytokine production [8384].

Allergen-Elimination Diets

In animal studies, TSLP mediated allergic responses with eczema caused by food allergens such as egg, peanut, and pigeon pea proteins [858687].

Food allergies are highly associated with the incidence and worsening of eczema, especially in children. In a study, 33-63% of children with atopic dermatitis were estimated to be allergic to foods such as cow’s milk, eggs, peanuts, wheat, soy, nuts, or fish [8889].

Adolescents and adults are less likely to react to these foods, but those allergic to pollen may develop eczema in response to cross-reacting foods such as green apple, carrots, hazelnut, celery, and pear [8990].

Alternatively, people already sensitized to some substances through skin contact may develop eczema after ingesting them. Common allergens include balsam of Peru (found in flavorings, spices, and certain foods), nickel (found in whole wheat bread, oatmeal, legumes, soy, shellfish, and processed meats), and propylene glycol (found in processed foods) [919293].

Avoiding the specific food trigger can help prevent the development or worsening of eczema, but only in people with a proven allergy [9495].

Vitamin E

In mice, vitamin E ingestion directly reduced TSLP levels [5196].

In 3 clinical trials of people with eczema, supplementation with high doses of vitamin E improved the symptoms and quality of life [535354].

Black Seed

While its effects on TSLP directly are unknown, black seed oil (also known as black cumin oil) improves all of the major downstream effects of TSLP. In various studies, black seed oil has reduced the overall Th2 response, prevented mast cell activation, and reduced IgE production [979899].

In a clinical trial of people with hand eczema, topical black seed oil improved the symptoms as effectively as the corticosteroid betamethasone [100].

In breast cancer patients, a gel with 5% black seed oil reduced the severity and delayed the onset of radiation dermatitis [101].

Probiotics

In mice with eczema and asthma, administering a Lactobacillus rhamnosus strain (Lcr35) restored the levels of TSLP and other inflammatory cytokines back to normal. In gut lining cells, Lactobacillus and Bifidobacterium strains from the normal human microbiota reduced TSLP levels [102103104].

In people with eczema, supplementation with different probiotic strains slightly improved skin inflammation. The most common Lactobacillus species tested include L. rhamnosusL.reuteriL. plantarumL. paracaseiL. fermentum, and L. sakei [34567879].

Bifidobacterium species such as B. animalisB. breve, and B. longum have been mainly tested in combination with Lactobacillus strains. The studies produced mixed results, possibly due to differences in the strains used [31011121314].

Preventive prenatal maternal or postnatal pediatric supplementation with combinations of some of these Lactobacillus and Bifidobacterium strains in families with a history of atopic disease significantly lowered the incidence of eczema in children [15164171819202021222324].

CXCR5

Stress Management

Higher CXCR5 levels have been measured in the blood of people suffering from anxiety disorders such as PTSD and panic disorder [105106].

The hormones released during chronic stress are believed to increase skin inflammation and enhance the Th2 response, potentially leading to higher incidence and severity of both seborrheic and atopic dermatitis [107108109110].

A meta-analysis concluded that psychological interventions aimed at reducing stress may improve eczema severity, itching intensity, and scratching [111].

We recommend addressing sources of stress in your life, either by taking up a stress-busting hobby (such as yoga or meditation) or seeking professional help.

Allergen-Elimination Diets

In a clinical trial of children with allergy to eggs, including baked eggs in the diet increased the production of CXCR5-producing T cells [112].

Food allergies are highly associated with the incidence and worsening of eczema, especially in children. In a study, 33-63% of children with atopic dermatitis were estimated to be allergic to foods such as cow’s milk, eggs, peanuts, wheat, soy, nuts, or fish [8889].

Adolescents and adults are less likely to react to these foods, but those allergic to pollen may develop eczema in response to cross-reacting foods such as green apple, carrots, hazelnut, celery, and pear [8990].

Alternatively, people already sensitized to some substances through skin contact may develop eczema after ingesting them. Common allergens include balsam of Peru (found in flavorings, spices, and certain foods), nickel (found in whole wheat bread, oatmeal, legumes, soy, shellfish, and processed meats), and propylene glycol (found in processed foods) [919293].

Avoiding the specific food trigger can help prevent the development or worsening of eczema, but only in people with a proven allergy [9495].

BCL6

Sunlight Exposure/Vitamin D

Vitamin D blocks the production of IL-4 and other inflammatory molecules. In line with this, a gene variant resulting in higher IL-4 levels has been associated with increased risk of allergies in people with vitamin D deficiency [113114].

Studies have associated low blood vitamin D levels with eczema (atopic dermatitis) in children. In people with food sensitization, those with the lowest vitamin D levels had more severe eczema [36373839].

A healthy exposure to sunlight is the best way of increasing your blood vitamin D levels. In addition, you can eat food sources of this vitamin (such as fatty fish, liver, egg yolks, and dairy) [40].

Research also suggests that vitamin D supplementation can improve eczema severity, although some studies found it ineffective [37414243].

Reducing Stress

The hormones released during chronic stress block BCL6 production and increase IL-4 levels, ultimately enhancing the Th2 response. This may lead to higher incidence and severity of both seborrheic and atopic dermatitis [115116109110].

A meta-analysis concluded that psychological interventions aimed at reducing stress may improve eczema severity, itching intensity, and scratching [111].

We recommend addressing sources of stress in your life, either by taking up a stress-busting hobby (such as yoga or meditation) or seeking professional help.

Acupuncture

In mice with eczema, acupuncture treatment improved skin inflammation and lowered the levels of IL-4, other inflammatory cytokines, and allergy-related antibodies (IgE) [117118].

A meta-analysis of 8 studies found acupuncture effective at reducing the symptoms and severity of eczema. However, the authors warned that all the studies compared acupuncture with no treatment or with conventional medication instead of using a more suitable negative control (“sham” or fake acupuncture) [50].

Massage

A single session of Swedish massage decreased the levels of IL-4 and other inflammatory cytokines in a clinical trial of healthy volunteers. Similarly, scalp massage was especially effective at lowering IL-4 levels in a clinical trial of breast cancer patients [119120].

In two clinical trials on children with eczema, massage improved symptoms such as redness, itching, and scaling. Because the use of essential oils provided no additional effects, physical contact is believed to account for the benefits of massage [121122].

Fermented Foods

The intake of fermented soybean and Japanese apricot improved skin inflammation by lowering the levels of IL-4, other inflammatory cytokines, T cells producing them, and allergy-related antibodies (IgE) in mice with eczema [123124125126].

Bacterial strains isolated from fermented Asian foods such as kimchi and jeotgal had similar effects [127128129130131].

In adults, diets rich in fermented foods such as kimchi, fermented seafood, and pickled have been associated with a reduced incidence of eczema. In children, the intake of yogurt showed similarly protective effects [132133134135].

In a clinical trial, orange juice fermented with a Lactobacillus plantarum strain improved the symptoms and quality of life in people with mild to moderate eczema [6].

The intake of fermented foods such as yogurt and natto by pregnant women helped prevent eczema in their children during their first 2 years of life. However, a study suggests that other fermented foods such as miso soup eaten during breastfeeding may have the opposite effects and should be avoided [136137138].

In some cases, fermented foods may help by providing beneficial microorganisms. Other foods don’t contain alive microorganisms (e.g., if they have been heat-killed) but supply the beneficial metabolites produced during the fermentation process [132].

Quercetin/Vegetarian Diet

In mice with eczema, the oral administration of quercetin improved skin inflammation and reduced IL-4 levels [139140].

In a clinical trial of people with eczema (atopic dermatitis), a vegetarian diet improved the symptoms and reduced the levels of white blood cells (eosinophils and neutrophils). The authors of the study attributed the effects of this diet to its high content in flavonoids, especially quercetin [141142].

Supplementation with quercetin, as well as with a rich source of this flavonoid (dodder seed extract), improved contact and atopic dermatitis in two small trials [143144].

Food sources of this flavonoid include vegetables such as capers, onions, eggplant, celery, and asparagus, fruits such as berries, apples, and oranges, nuts, and tea (both green and black) [145].

Avoiding Cow Milk Formula

A study in rat pups found that formula feeding increased the levels of IL-4, other inflammatory cytokines, and allergy-related antibodies (IgE) when compared to breastfeeding [146].

According to a meta-analysis, exclusive breastfeeding protects children with a family history of allergic diseases from developing atopic dermatitis. Partially hydrolyzed whey formula also provided some advantage over cow milk formula, but less than breastfeeding [147148149].

Shea Butter

Shea butter triterpenes, especially lupeol, reduce skin inflammation in part by preventing the production of IL-4. The levels of this cytokine may be high in people with underactive BCL6 variants. Shea butter also reduces the production of other pro-inflammatory cytokines, prostaglandins, and myeloperoxidase [150151152153154].

Topical creams containing shea butter improved redness, swelling, dryness, and itching in children and adolescents with mild-to-moderate eczema in 3 clinical trials [155156157].

Licorice

Applying a compound isolated from licorice (isoliquiritigenin) on the skin of mice with eczema improved the symptoms and reduced the levels of IL-4 and other inflammatory cytokines [158].

A gel with 1-2% of licorice root reduced skin redness, itching, and swelling in people with eczema. A different herbal formulation with licorice root, willow bark, and gentian root extracts had anti-inflammatory effects comparable to those of hydrocortisone in another study [5960].

Similarly, formulations containing licorice’s active compound licochalcone A, applied on the face, forearms, and scalp, improved skin itching, inflammation, redness, and dryness as effectively as hydrocortisone [616263646566].

Niacinamide

A cell-based study found that niacinamide may exert its anti-inflammatory effects in part by increasing BCL6 levels [159].

Niacinamide 2% cream reduced skin water loss and improved skin hydration in patients with atopic dermatitis when applied 2x/day for 2 months [160].

In people with facial seborrheic dermatitis, niacinamide 4% cream reduced symptoms such as redness and scaling by 75% after 3 months [161].

Milk Thistle (Silymarin)

In mice with eczema, application of silymarin from milk thistle on the skin improved inflammation and lowered the blood levels of IL-4 and allergy-related antibodies (IgE) [162].

Silymarin formulated into a cream prevented dermatitis from radiotherapy in 2 trials of breast cancer patients [5657].

Probiotics

Supplementation with probiotics strains of Lactobacillus plantarumL. paracasei, and L. fermentum strains improved skin inflammation and reduced the levels of IL-4, other inflammatory cytokines, and allergy-related antibodies (IgE) in two clinical trials of children with eczema [1637].

Probiotics were similarly effective in multiple mouse studies [164165166102167103168169].

In people with eczema, supplementation with different probiotic strains slightly improved skin inflammation. The most common Lactobacillus species tested include L. rhamnosusL.reuteriL. plantarumL. paracaseiL. fermentum, and L. sakei [34567879].

Bifidobacterium species such as B. animalisB. breve, and B. longum have been mainly tested in combination with Lactobacillus strains. The studies produced mixed results, possibly due to differences in the strains used [31011121314].

Preventive prenatal maternal or postnatal pediatric supplementation with combinations of some of these Lactobacillus and Bifidobacterium strains in families with a history of atopic disease significantly lowered the incidence of eczema in children [15164171819202021222324].

Prebiotic Oligosaccharides

In mice with eczema, two different prebiotic oligosaccharides improved skin inflammation by lowering the levels of IL-4 and other inflammatory cytokines [170171].

Prebiotics contain non-digestible ingredients that stimulate the development and activity of beneficial gut bacteria. A lot of them are oligosaccharides, a class of carbohydrates formed by a small number of sugar molecules [172].

In a few clinical trials, feeding newborns with formula containing galacto-oligosaccharides, fructo-oligosaccharides, or their combination prevented eczema during the first years of life and improved the symptoms in those already suffering from this condition [173174175176177178179180].

Black Seed

Both oral and topical preparations with black seed oil’s active component thymoquinone improved skin inflammation and reduced the blood levels of IL-4 and allergy-related antibodies (IgE) in mice with eczema [181].

In a clinical trial of people with hand eczema, topical black seed oil improved the symptoms as effectively as the corticosteroid betamethasone [100].

In breast cancer patients, a gel with 5% black seed oil reduced the severity and delayed the onset of radiation dermatitis [101].

One review of 4 studies concluded that oral black seed oil may help with allergic symptoms, including eczema, when used as an add-on to conventional therapy [182].

Melatonin

In mice with eczema, the intake of melatonin reduced total allergy-related antibodies (IgE) in blood, and IL-4 and IFN-gamma production by T cells [183].

Melatonin supplementation improved both disease severity and sleep disturbances in 2 clinical trials on children with eczema [184185].

STAT6

Acupuncture

In a mouse study, acupuncture reduced STAT6 activity and reduced inflammation in allergic rhinitis, or hay fever [186].

A meta-analysis of 8 studies found acupuncture effective at reducing the symptoms and severity of eczema. However, the authors warned that all the studies compared acupuncture with no treatment or with conventional medication instead of using a more suitable negative control (“sham” or fake acupuncture) [50].

Allergen-Elimination Diets

A study associated the ‘CC’ genotype of rs3024974 with allergies (with symptoms including skin reactions) to foods such as shrimps, eggs, eggplants, milk, bananas, and peanuts in children and adolescents [187].

Food allergies are highly associated with the incidence and worsening of eczema, especially in children. In a study, 33-63% of children with atopic dermatitis were estimated to be allergic to foods such as cow’s milk, eggs, peanuts, wheat, soy, nuts, or fish [8889].

Adolescents and adults are less likely to react to these foods, but those allergic to pollen may develop eczema in response to cross-reacting foods such as green apple, carrots, hazelnut, celery, and pear [8990].

Alternatively, people already sensitized to some substances through skin contact may develop eczema after ingesting them. Common allergens include balsam of Peru (found in flavorings, spices, and certain foods), nickel (found in whole wheat bread, oatmeal, legumes, soy, shellfish, and processed meats), and propylene glycol (found in processed foods) [919293].

Avoiding the specific food trigger can help prevent the development or worsening of eczema, but only in people with a proven allergy [9495].

Avoiding Processed Foods

The food additive may activate STAT6, according to an animal study [188].

Two studies associated a dietary pattern rich in processed foods with an increased incidence of eczema [132134].

The additives found in these foods are believed to function as pseudo-allergens that may trigger or worsen eczema. In line with this, restricting the intake of the additive monosodium glutamate improved eczema symptoms and reduced the levels of a protein released during food allergic reactions in children [189190].

Fatty Fish (Omega-3)

In cell based studies, the omega-3 fatty acids docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) reduced STAT6 levels and activation [191192].

A meta-analysis associated high intake of fatty fish and omega-3 fatty acids by pregnant women with a reduced incidence of eczema and allergies in their children [193].

Because omega-3 supplementation trials produced mixed results, it may be preferable to ensure a sufficient dietary intake of these fatty acids. Fatty fish such as mackerel, salmon, sardines, and herrings are the best dietary sources [194195196197198199200].

Vegetarian Diet (Apigenin)

In mice with eczema, including apigenin in the diet improved skin lesions, reduced inflammatory markers, and blocked the activation of STAT6 [201].

In a clinical trial of people with eczema (atopic dermatitis), a vegetarian diet improved the symptoms and reduced the levels of white blood cells (eosinophils and neutrophils). The authors of the study attributed the effects of this diet to its high content in flavonoids such as apigenin and quercetin [141142].

Food sources of apigenin include parsley, onions, artichokes, oranges, tea, chamomile, wheat sprouts, and some seasonings.

Vitamin E

In human cells, vitamin E blocks IL-13 signalling. Since IL-13 stimulates STAT6, this may be a good way to prevent STAT6 activation [202].

In 3 clinical trials of people with eczema, supplementation with high doses of vitamin E improved the symptoms and quality of life [535354].

CCR7

Reducing Stress

In mice with eczema, stress (from social defeat) worsened skin inflammation by increasing CCR7 levels in antigen-presenting cells (dendritic cells). Interestingly, engineered mice lacking CCR7 showed fewer anxious behaviors in response to maternal separation [203204].

The hormones released during chronic stress are believed to increase skin inflammation and enhance the Th2 response, potentially leading to higher incidence and severity of both seborrheic and atopic dermatitis [107108109110].

A meta-analysis concluded that psychological interventions aimed at reducing stress may improve eczema severity, itching intensity, and scratching [111].

We recommend addressing sources of stress in your life, either by taking up a stress-busting hobby (such as yoga or meditation) or seeking professional help.

Sunlight Exposure/Vitamin D

Vitamin D deficiency is associated with inflammation, partly due to excess CCR7 activity in immune cells [205206207].

Studies have associated low blood vitamin D levels with eczema (atopic dermatitis) in children. In people with food sensitization, those with the lowest vitamin D levels had more severe eczema [36373839].

A healthy exposure to sunlight is the best way of increasing your blood vitamin D levels. In addition, you can eat food sources of this vitamin (such as fatty fish, liver, egg yolks, and dairy) [40].

Research also suggests that vitamin D supplementation can improve eczema severity, although some studies found it ineffective [37414243].

Thunder God Vine

Triptolide, an active component of thunder god vine, may exert its immunosuppressive effects by reducing CCR7 levels, ultimately preventing the maturation and migration of antigen-presenting cells (dendritic cells) [208209].

A meta-analysis of 13 clinical trials found thunder god vine effective at treating eczema, especially in combination with conventional medication. However, the authors warned about its potential adverse effects and the small size of most studies [210].

Hemp Seed Oil

In a study in white blood cells (monocytes), hemp seed proteins lowered CCR7 levels [211].

Hemp seeds are also rich in polyunsaturated fatty acids with potential benefits to skin health such as the omega-3 alpha-linolenic acid (ALA) and the omega-6 linoleic and gamma-linolenic acid (GLA) [212].

In a small trial on people with eczema, dietary hemp seed oil increased blood levels of the above-mentioned fatty acids and reduced skin dryness, itching, and medication use [213].

SMAD3

Light Therapy

Skin irradiation with ultraviolet A (UVA) radiation reduced the levels of both SMAD3 and TGF-beta in 2 small trials of healthy volunteers and people with localized scleroderma. However, UVB radiation may have the opposite effect [214215216].

Ultraviolet (UV) radiation has been most extensively used for eczema, especially in severe cases. While UVA is more effective to improve flares (especially if combined with the photosensitizer psoralen), UVB is preferable to manage chronic eczema. Importantly, UVB is less likely than UVA to cause skin cancer [76777879].

UV radiation helps with eczema by inhibiting inflammation and the immune response, making the skin thicker, and killing potentially infectious skin bacteria [808182].

Blue light therapy helped reduce disease severity, itching, and number of lesions in 2 trials on people with eczema. In one of them, blue light was shown to reduce T cell activation and cytokine production [8384].

Quercetin

Quercetin blocked the TGF-beta/SMAD3 pathway in multiple animal and cell-based studies [217218219220].

In a clinical trial of people with eczema (atopic dermatitis), a vegetarian diet improved the symptoms and reduced the levels of white blood cells (eosinophils and neutrophils). The authors of the study attributed the effects of this diet to its high content in flavonoids, especially quercetin [141142].

Supplementation with quercetin, as well as with a rich source of this flavonoid (dodder seed extract), improved contact and atopic dermatitis in two small trials [143144].

Food sources of this flavonoid include vegetables such as capers, onions, eggplant, celery, and asparagus, fruits such as berries, apples, and oranges, nuts, and tea (both green and black) [145].

Vitamin E

In mice, increased vitamin E intake prevented tissue damage from elevated TGF-beta [221].

In 3 clinical trials of people with eczema, supplementation with high doses of vitamin E improved the symptoms and quality of life [535354].

Licorice

In mice, licorice’s active compound glycyrrhizin reduced skin scarring by reducing the levels of both SMAD3 and TGF-beta. Another compound from licorice, glycyrrhetinic acid, had the same effects in cells [222223].

A gel with 1-2% of licorice root reduced skin redness, itching, and swelling in people with eczema. A different herbal formulation with licorice root, willow bark, and gentian root extracts had anti-inflammatory effects comparable to those of hydrocortisone in another study [5960].

Similarly, formulations containing licorice’s active compound licochalcone A, applied on the face, forearms, and scalp, improved skin itching, inflammation, redness, and dryness as effectively as hydrocortisone [616263646566].

Thunder God Vine

Active components isolated from thunder god vine reduced SMAD3 and TGF-beta levels in several rat studies [224225226].

A meta-analysis of 13 clinical trials found thunder god vine effective at treating eczema, especially in combination with conventional medication. However, the authors warned about its potential adverse effects and the small size of most studies [210].

Melatonin

In multiple animal studies, melatonin supplementation prevented scarring in different tissues by blocking the TGF-beta/SMAD3 pathway [227228229230231].

Melatonin supplementation improved both disease severity and sleep disturbances in 2 clinical trials on children with eczema [184185].

IL13

Light Therapy

One small study found UVA light therapy to lower levels of IL-13 in patients with eczema. However, a similar study found no significant differences in IL-13 levels of eczema patients after UVA light therapy [232233].

Ultraviolet (UV) radiation has been most extensively used for eczema, especially in severe cases. While UVA is more effective to improve flares (especially if combined with the photosensitizer psoralen), UVB is preferable to manage chronic eczema. Importantly, UVB is less likely than UVA to cause skin cancer [76777879].

UV radiation helps with eczema by inhibiting inflammation and the immune response, making the skin thicker, and killing potentially infectious skin bacteria [808182].

Blue light therapy helped reduce disease severity, itching, and number of lesions in 2 trials on people with eczema. In one of them, blue light was shown to reduce T cell activation and cytokine production [8384].

Reducing Stress

In a study of healthy medical students, academic examination stress increased the blood levels of IL-13 and other inflammatory cytokines [234].

A meta-analysis concluded that psychological interventions aimed at reducing stress may improve eczema severity, itching intensity, and scratching [111].

We recommend addressing sources of stress in your life, either by taking up a stress-busting hobby (such as yoga or meditation) or seeking professional help.

Avoiding Cigarette Smoke

In mice, exposure to a chemical from cigarette smoke (benzopyrene) increased IL-13 levels in the skin [235].

A meta-analysis of studies associated both mild and extensive exposure to cigarette smoke (especially by actively smoking) with an increased incidence of eczema (atopic dermatitis). Cigarette smoke is believed to impair the skin barrier function and alter the immune system [236].

Massage

In a clinical trial of healthy volunteers, a single session of Swedish massage lowered the levels of IL-13 and other inflammatory cytokines [237].

In two clinical trials on children with eczema, massage improved symptoms such as redness, itching, and scaling. Because the use of essential oils provided no additional effects, physical contact is believed to account for the benefits of massage [121122].

Allergen-Elimination Diets

In one study, immune system cells obtained from children whose eczema worsened after consumption of milk and eggs were observed to release significant amounts of Th2 proteins. This suggests that eliminating certain foods from the diet may improve allergies by decreasing the release of Th2 proteins, including IL-13 [238239].

Food allergies are highly associated with the incidence and worsening of eczema, especially in children. In a study, 33-63% of children with atopic dermatitis were estimated to be allergic to foods such as cow’s milk, eggs, peanuts, wheat, soy, nuts, or fish [8889].

Adolescents and adults are less likely to react to these foods, but those allergic to pollen may develop eczema in response to cross-reacting foods such as green apple, carrots, hazelnut, celery, and pear [8990].

Alternatively, people already sensitized to some substances through skin contact may develop eczema after ingesting them. Common allergens include balsam of Peru (found in flavorings, spices, and certain foods), nickel (found in whole wheat bread, oatmeal, legumes, soy, shellfish, and processed meats), and propylene glycol (found in processed foods) [919293].

Avoiding the specific food trigger can help prevent the development or worsening of eczema, but only in people with a proven allergy [9495].

Fermented Foods

In mice with eczema, the intake of fermented rice bran and legume products improved skin inflammation by lowering the levels of IL-13 and other inflammatory cytokines. Similarly, fermented ginseng reduced this and other cytokines in mice with allergic rhinitis [240125241].

In adults, diets rich in fermented foods such as kimchi, fermented seafood, and pickled have been associated with a reduced incidence of eczema. In children, the intake of yogurt showed similarly protective effects [132133134135].

In a clinical trial, orange juice fermented with a Lactobacillus plantarum strain improved the symptoms and quality of life in people with mild to moderate eczema [6].

The intake of fermented foods such as yogurt and natto by pregnant women helped prevent eczema in their children during their first 2 years of life. However, a study suggests that other fermented foods such as miso soup eaten during breastfeeding may have the opposite effects and should be avoided [136137138].

In some cases, fermented foods may help by providing beneficial microorganisms. Other foods don’t contain alive microorganisms (e.g., if they have been heat-killed) but supply the beneficial metabolites produced during the fermentation process [132].

Fatty Fish (Omega-3)

Two meta-analyses associated high intake of fatty fish and omega-3 fatty acids by pregnant women with a reduced incidence of eczema and allergies in their children, as well as lower IL-13 levels. Omega-3s also lowered the activity of this cytokine in cell-based studies [193242192243].

Because omega-3 supplementation trials produced mixed results, it may be preferable to ensure a sufficient dietary intake of these fatty acids. Fatty fish such as mackerel, salmon, sardines, and herrings are the best dietary sources [194195196197198199200].

Zinc

Eating a zinc-deficient diet worsened eczema and increased IL-13 production in a mouse study [244].

Zinc deficiency (determined as low zinc levels in the blood and hair) was associated with increased odds of eczema (atopic dermatitis) in a meta-analysis. However, the authors warned about the low quality of most included studies [245].

Good dietary sources of zinc include red meat, seafood, dairy products, nuts, legumes, and whole grains [246].

Vegetarian Diet (Quercetin)

The egg protein ovalbumin lost its ability to trigger allergic reactions in cells when combined with quercetin. Mice fed this combination had lower levels of IL-13 and other inflammatory cytokines. Similarly, quercetin reduced the production of this and other cytokines by T cells [247248].

In a clinical trial of people with eczema (atopic dermatitis), a vegetarian diet improved the symptoms and reduced the levels of white blood cells (eosinophils and neutrophils). The authors of the study attributed the effects of this diet to its high content in flavonoids, especially quercetin [141142].

Food sources of this flavonoid include vegetables such as capers, onions, eggplant, celery, and asparagus, fruits such as berries, apples, and oranges, nuts, and tea (both green and black) [145].

Black Seed

In mice with different inflammatory conditions, treatment with different active components of black seed oil lowered IL-13 levels [249250251].

In a clinical trial of people with hand eczema, topical black seed oil improved the symptoms as effectively as the corticosteroid betamethasone [100].

In breast cancer patients, a gel with 5% black seed oil reduced the severity and delayed the onset of radiation dermatitis [101].

Aloe Vera

Complex carbohydrates from aloe vera reduced the levels of IL-13 and other Th2 cytokines in mice with food allergies [252].

A gel with aloe vera among other ingredients was effective at improving mild to moderate seborrheic dermatitis in a small trial [253].

Aloe vera improved diaper rash in another study, although marigold ointment was more effective [254].

Examination gloves delivering aloe vera improved skin integrity and reduced wrinkles and redness in people with contact dermatitis [255].

Cannabidiol (CBD)

Cannabidiol (CBD) lowered the levels of IL-13 and other inflammatory cytokines in asthmatic mice [256].

In a small trial on people with eczema and other skin conditions, an ointment containing CBD (without THC) improved the symptoms and skin parameters such as hydration, barrier function, and elasticity [69].

The anti-inflammatory effects of CBD in a cell-based study suggest it may also help with allergic dermatitis [70].

Dwarf Elder

Dwarf elder extract reduced the levels of IL-13 and other inflammatory cytokines in the airways of asthmatic mice challenged with an egg protein (ovalbumin) [257].

In a small clinical trial on people with eczema caused by contact with beetles, applying dwarf elder extract in combination with hydrocortisone reduced burning and inflammation better than hydrocortisone alone [258].

Probiotics

In a randomized controlled trial focused on children with asthma and hay fever, 8-week daily supplementation of L. gasseri was found to significantly reduce IL-13 production [259].

In people with eczema, supplementation with different probiotic strains slightly improved skin inflammation. The most common Lactobacillus species tested include L. rhamnosusL.reuteriL. plantarumL. paracaseiL. fermentum, and L. sakei [34567879].

Bifidobacterium species such as B. animalisB. breve, and B. longum have been mainly tested in combination with Lactobacillus strains. The studies produced mixed results, possibly due to differences in the strains used [31011121314].

Preventive prenatal maternal or postnatal pediatric supplementation with combinations of some of these Lactobacillus and Bifidobacterium strains in families with a history of atopic disease significantly lowered the incidence of eczema in children [15164171819202021222324].

Thunder God Vine

An active compound of thunder god vine (triptolide) inhibited IL-13 production by T cells [260].

A meta-analysis of 13 clinical trials found thunder god vine effective at treating eczema, especially in combination with conventional medication. However, the authors warned about its potential adverse effects and the small size of most studies [210].

PTGER4

Sunlight Exposure/Vitamin D

Researchers suspect that there could be an important interaction between vitamin D and the prostaglandin pathway. Intriguingly, the vitamin D receptor (VDR) may bind to a region of DNA that regulates PTGER4 expression. This relationship is of particular interest to researchers studying multiple sclerosis, a degenerative autoimmune disease, but it could also help explain why sunlight and vitamin D improve allergies [261].

Studies have associated low blood vitamin D levels with eczema (atopic dermatitis) in children. In people with food sensitization, those with the lowest vitamin D levels had more severe eczema [36373839].

A healthy exposure to sunlight is the best way of increasing your blood vitamin D levels. In addition, you can eat food sources of this vitamin (such as fatty fish, liver, egg yolks, and dairy) [40].

Research also suggests that vitamin D supplementation can improve eczema severity, although some studies found it ineffective [37414243].

Fatty Fish (Omega-3)

In a clinical trial of pregnant women, increasing dietary intake of salmon (rich in omega-3 fatty acids) reduced the production of PGE2 and other inflammatory mediators in cord blood mononuclear cells. In mice with eczema, supplementation with omega-3 fatty acids lowered blood PGE2 levels [262263].

A meta-analysis associated high intake of fatty fish and omega-3 fatty acids by pregnant women with a reduced incidence of eczema and allergies in their children [193].

Because omega-3 supplementation trials produced mixed results, it may be preferable to ensure a sufficient dietary intake of these fatty acids. Fatty fish such as mackerel, salmon, sardines, and herrings are the best dietary sources [194195196197198199200].

Licorice

Licochalcone A, a compound isolated from licorice, showed multiple anti-inflammatory effects in animal and cell-based studies, including the reduction of PGE2 levels [264265266267268].

A gel with 1-2% of licorice root reduced skin redness, itching, and swelling in people with eczema. A different herbal formulation with licorice root, willow bark, and gentian root extracts had anti-inflammatory effects comparable to those of hydrocortisone in another study [5960].

Similarly, formulations containing licorice’s active compound licochalcone A, applied on the face, forearms, and scalp, improved skin itching, inflammation, redness, and dryness as effectively as hydrocortisone [616263646566].

Chamomile

Chamomile showed anti-inflammatory effects including the reduction of PGE2 levels in cell-based studies. Its flavonoids act as inhibitors of a key enzyme in PGE2 production (COX2) [269270271].

Applying a cream with 2% chamomile extract improved skin itching, redness, and scaling more effectively than some conventional anti-inflammatory creams in 2 clinical trials. However, the extract was ineffective in another trial [272273274].

Vitamin E

Supplementation with vitamin E prevented PGE2 production in elderly people and old mice, possibly by blocking a key enzyme in this process (COX2) [275276277].

In 3 clinical trials of people with eczema, supplementation with high doses of vitamin E improved the symptoms and quality of life [5327854].

IL7R

Reducing Stress

In mice, chronic stress from hostile social interactions caused increased IL-7 levels [279].

A meta-analysis concluded that psychological interventions aimed at reducing stress may improve eczema severity, itching intensity, and scratching [111].

We recommend addressing sources of stress in your life, either by taking up a stress-busting hobby (such as yoga or meditation) or seeking professional help.

Sunlight Exposure/Vitamin D

Some variants of the IL7R gene have been associated with vitamin D deficiency in humans. Furthermore, vitamin D may stimulate the development of Tregs, which may counteract the effects of IL7R receptor binding [280281282].

Vitamin D has also been found to reduce JAK/STAT signalling in cell studies [283284285].

Studies have associated low blood vitamin D levels with eczema (atopic dermatitis) in children. In people with food sensitization, those with the lowest vitamin D levels had more severe eczema [36373839].

A healthy exposure to sunlight is the best way of increasing your blood vitamin D levels. In addition, you can eat food sources of this vitamin (such as fatty fish, liver, egg yolks, and dairy) [40].

Research also suggests that vitamin D supplementation can improve eczema severity, although some studies found it ineffective [37414243].

Vegetarian Diet/Quercetin

Quercetin is a plant flavonoid and antioxidant recognized as one of the best natural antihistamines. It has been found to block a cellular pathway that activates the IL7R receptor [286].

In a clinical trial of people with eczema (atopic dermatitis), a vegetarian diet improved the symptoms and reduced the levels of white blood cells (eosinophils and neutrophils). The authors of the study attributed the effects of this diet to its high content in flavonoids, especially quercetin [141142].

Supplementation with quercetin, as well as with a rich source of this flavonoid (dodder seed extract), improved contact and atopic dermatitis in two small trials [143144].

Food sources of this flavonoid include vegetables such as capers, onions, eggplant, celery, and asparagus, fruits such as berries, apples, and oranges, nuts, and tea (both green and black) [145].

Green Tea (EGCG)

Green tea’s active component epigallocatechin gallate (EGCG) blocked IL-7 activity in T cells, possibly by preventing IL7R production [287].

In breast cancer patients with dermatitis caused by radiation therapy, topical application of green tea’s active component epigallocatechin gallate (EGCG) reduced pain, burning, itching, pulling, and tenderness [288].

Similarly, a cream with EGCG, grape seed procyanidins, and vitamin E improved eczema (atopic dermatitis) in a preliminary clinical trial [289].

NFATC2

Probiotics

Probiotics are live strains of beneficial bacteria that may improve allergies by reducing Th2 activity, including the production of IL-4 and IL-13 [290].

In people with eczema, supplementation with different probiotic strains slightly improved skin inflammation. The most common Lactobacillus species tested include L. rhamnosusL.reuteriL. plantarumL. paracaseiL. fermentum, and L. sakei [34567879].

Bifidobacterium species such as B. animalisB. breve, and B. longum have been mainly tested in combination with Lactobacillus strains. The studies produced mixed results, possibly due to differences in the strains used [31011121314].

Preventive prenatal maternal or postnatal pediatric supplementation with combinations of some of these Lactobacillus and Bifidobacterium strains in families with a history of atopic disease significantly lowered the incidence of eczema in children [15164171819202021222324].

MICA

Sunlight Exposure/Vitamin D

Vitamin D has been found to significantly decrease MICA activity in a lab setting [291292].

Studies have associated low blood vitamin D levels with eczema (atopic dermatitis) in children. In people with food sensitization, those with the lowest vitamin D levels had more severe eczema [36373839].

A healthy exposure to sunlight is the best way of increasing your blood vitamin D levels. In addition, you can eat food sources of this vitamin (such as fatty fish, liver, egg yolks, and dairy) [40].

Research also suggests that vitamin D supplementation can improve eczema severity, although some studies found it ineffective [37414243].

RORC

Sunlight Exposure/Vitamin D

Exposure to vitamin D reduced RORC-gamma levels in white blood cells (macrophages). In T cells, it also prevented their development into Th17 cells [293294].

Studies have associated low blood vitamin D levels with eczema (atopic dermatitis) in children. In people with food sensitization, those with the lowest vitamin D levels had more severe eczema [36373839].

A healthy exposure to sunlight is the best way of increasing your blood vitamin D levels. In addition, you can eat food sources of this vitamin (such as fatty fish, liver, egg yolks, and dairy) [40].

Research also suggests that vitamin D supplementation can improve eczema severity, although some studies found it ineffective [37414243].

Probiotics

In a clinical study of 75 overweight people, eating yogurt (containing probiotic Lactobacillus strains) every day for eight weeks decreased ROR-gamma activity, among other inflammatory markers [295].

In people with eczema, different probiotic strains slightly improved skin inflammation. The most common Lactobacillus species tested include L. rhamnosusL.reuteriL. plantarumL. paracaseiL. fermentum, and L. sakei [34567879].

Bifidobacterium species such as B. animalisB. breve, and B. longum have been mainly tested in combination with Lactobacillus strains. The studies produced mixed results, possibly due to differences in the strains used [31011121314].

Preventive prenatal maternal or postnatal pediatric supplementation with combinations of some of these Lactobacillus and Bifidobacterium strains in families with a history of atopic disease significantly lowered the incidence of eczema in children [15164171819202021222324].

Vitamin E

A study of people who underwent the surgical removal of the tonsils associated high blood vitamin E with low levels of ROR-gamma and other inflammatory mediators [296].

In 3 clinical trials of people with eczema, supplementation with high doses of vitamin E improved the symptoms and quality of life [5327854].

GATA3

Licorice

An active component isolated from licorice (glycyrrhizic acid) reduced GATA3 production in T cells [297].

A gel with 1-2% of licorice root reduced skin redness, itching, and swelling in people with eczema. A different herbal formulation with licorice root, willow bark, and gentian root extracts had anti-inflammatory effects comparable to those of hydrocortisone in another study [5960].

Similarly, formulations containing licorice’s active compound licochalcone A, applied on the face, forearms, and scalp, improved skin itching, inflammation, redness, and dryness as effectively as hydrocortisone [616263646566].

Probiotics

probiotic mixture reduced eczema symptoms, suppressed the Th2 and Th17 responses, and lowered the level of multiple inflammatory mediators (including GATA3) in mice [166].

In people with eczema, supplementation with different probiotic strains slightly improved skin inflammation. The most common Lactobacillus species tested include L. rhamnosusL.reuteriL. plantarumL. paracaseiL. fermentum, and L. sakei [34567879].

Bifidobacterium species such as B. animalisB. breve, and B. longum have been mainly tested in combination with Lactobacillus strains. The studies produced mixed results, possibly due to differences in the strains used [31011121314].

Preventive prenatal maternal or postnatal pediatric supplementation with combinations of some of these Lactobacillus and Bifidobacterium strains in families with a history of atopic disease significantly lowered the incidence of eczema in children [15164171819202021222324].

Thunder God Vine

The main active compound of thunder god vine (triptolide) blocked IL-13 production by reducing GATA3 activity in T cells [260].

A meta-analysis of 13 clinical trials found thunder god vine effective at treating eczema, especially in combination with conventional medication. However, the authors warned about its potential adverse effects and the small size of most studies [210].

EMSY

Acupuncture

Acupuncture appears to help with allergic diseases by boosting IFN-gamma and changing the Th1/Th2 balance [298299].

A meta-analysis of 8 studies found acupuncture effective at reducing the symptoms and severity of eczema. However, the authors warned that all the studies compared acupuncture with no treatment or with conventional medication instead of using a more suitable negative control (“sham” or fake acupuncture) [50].

Probiotics

Several clinical trials have shown the potential of probiotic supplementation to increase IFN-gamma levels. In children, L. fermentum reduced atopic dermatitis severity by boosting IFN-gamma [300301302].

In people with eczema, supplementation with different probiotic strains slightly improved skin inflammation. The most common Lactobacillus species tested include L. rhamnosusL.reuteriL. plantarumL. paracaseiL. fermentum, and L. sakei [34567879].

Bifidobacterium species such as B. animalisB. breve, and B. longum have been mainly tested in combination with Lactobacillus strains. The studies produced mixed results, possibly due to differences in the strains used [31011121314].

Preventive prenatal maternal or postnatal pediatric supplementation with combinations of some of these Lactobacillus and Bifidobacterium strains in families with a history of atopic disease significantly lowered the incidence of eczema in children [15164171819202021222324].

SH2B3

Acupuncture

In one clinical study of asthma patients, acupuncture improved symptoms and reduced eosinophil numbers in the blood. In mice, acupuncture similarly reduced blood eosinophil counts, suggesting a reduced Th2 response [303304].

Reduced Th2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757072/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479426/

A meta-analysis of 8 studies found acupuncture effective at reducing the symptoms and severity of eczema. However, the authors warned that all the studies compared acupuncture with no treatment or with conventional medication instead of using a more suitable negative control (“sham” or fake acupuncture) [50].

ICE2

Light Therapy

In animals with allergic asthma, low-level laser therapy (LLLT, a type of specialized light therapy) reduced Th2 inflammation in the airway [305].

Ultraviolet (UV) radiation has been most extensively used for eczema, especially in severe cases. While UVA is more effective to improve flares (especially if combined with the photosensitizer psoralen), UVB is preferable to manage chronic eczema. Importantly, UVB is less likely than UVA to cause skin cancer [76777879].

UV radiation helps with eczema by inhibiting inflammation and the immune response, making the skin thicker, and killing potentially infectious skin bacteria [808182].

Blue light therapy helped reduce disease severity, itching, and number of lesions in 2 trials on people with eczema. In one of them, blue light was shown to reduce T cell activation and cytokine production [8384].

Vitamin E

Vitamin E is believed to play a central role in regulating the balance between Th1 and Th2 cell formation. If ICE2 is important for white blood cell transformation as some researchers suggest, then vitamin E could be part of the same regulatory systems [5152].

In 3 clinical trials of people with eczema, supplementation with high doses of vitamin E improved the symptoms and quality of life [535354].

NOD2

Maintaining a Healthy Weight

A study in mice found that NOD2 activity plays a key role in obesity-induced inflammation [306].

Two meta-analyses associated being overweight or obese with an increased incidence of eczema (atopic dermatitis) in both adults and children. In one of them, the association was significant in North American and Asian but not in European populations [307308].

Fatty Fish (Omega-3)

Omega-3 fatty acids have been found to reduce the activity of both NOD2 and TLR4 in pigs. It is likely that omega-3s mostly act on TLR4, with the side effect of reducing the requirement for NOD2 in response [309310].

A meta-analysis associated high intake of fatty fish and omega-3 fatty acids by pregnant women with a reduced incidence of eczema and allergies in their children [193].

Because omega-3 supplementation trials produced mixed results, it may be preferable to ensure a sufficient dietary intake of these fatty acids. Fatty fish such as mackerel, salmon, sardines, and herrings are the best dietary sources [194195196197198199200].

Probiotics

Most bacteria, including probiotics , have a protein called peptidoglycan on their surfaces. One study found that NOD2 is able to detect peptidoglycan and (rather than promote inflammation) stimulate the release of an anti-inflammatory cytokine in response. However, this effect might be limited to peptidoglycan of Lactobacillus strains [311312].

Another study suggested that L. gasseri OLL2809 in particular might be a good probiotic option for allergic diseases, as this strain was more effective at balancing the immune response when compared to other Lactobacillus strains. Specifically, L. gasseri OLL2809 was observed to significantly reduce Th2 activity and decrease IgE antibody release [313].

In people with eczema, supplementation with different probiotic strains slightly improved skin inflammation. The most common Lactobacillus species tested include L. rhamnosusL.reuteriL. plantarumL. paracaseiL. fermentum, and L. sakei [34567879].

Bifidobacterium species such as B. animalisB. breve, and B. longum have been mainly tested in combination with Lactobacillus strains. The studies produced mixed results, possibly due to differences in the strains used [31011121314].

Preventive prenatal maternal or postnatal pediatric supplementation with combinations of some of these Lactobacillus and Bifidobacterium strains in families with a history of atopic disease significantly lowered the incidence of eczema in children [15164171819202021222324].

IL1RL1/IL33

Maintaining a Healthy Weight

A study in humans and mice associated severe obesity with increased levels of both IL1RL1 and its activating cytokine IL-33 [314].

Two meta-analyses associated being overweight or obese with an increased incidence of eczema (atopic dermatitis) in both adults and children. In one of them, the association was significant in North American and Asian but not in European populations [307308].

Sunlight Exposure/Vitamin D

Interestingly, vitamin D has been shown to increase the production of a receptor that is closely related to IL1RL1. While this receptor can still bind IL-33, it can’t mediate the release of Th2-related cytokines, and thus effectively functions as a decoy. This is because it’s found free-floating, rather than connected to immune system cells [315].

Increased production of the IL1RL1 decoy has been suggested to reduce the IL-33-mediated release of Th2-related cytokines, due to reduced binding of IL-33 to IL1RL1 [315].

Studies have associated low blood vitamin D levels with eczema (atopic dermatitis) in children. In people with food sensitization, those with the lowest vitamin D levels had more severe eczema [36373839].

A healthy exposure to sunlight is the best way of increasing your blood vitamin D levels. In addition, you can eat food sources of this vitamin (such as fatty fish, liver, egg yolks, and dairy) [40].

Research also suggests that vitamin D supplementation can improve eczema severity, although some studies found it ineffective [37414243].

Acupuncture

Acupuncture blocked the IL-33/IL1RL1 pathway by lowering the levels of both proteins in two mouse studies [316317].

A meta-analysis of 8 studies found acupuncture effective at reducing the symptoms and severity of eczema. However, the authors warned that all the studies compared acupuncture with no treatment or with conventional medication instead of using a more suitable negative control (“sham” or fake acupuncture) [50].

Allergen-Elimination Diets

Engineered mice lacking both IL1RL1 and IL33 were protected against the development of food allergies in a study [318].

Food allergies are highly associated with the incidence and worsening of eczema, especially in children. In a study, 33-63% of children with atopic dermatitis were estimated to be allergic to foods such as cow’s milk, eggs, peanuts, wheat, soy, nuts, or fish [8889].

Adolescents and adults are less likely to react to these foods, but those allergic to pollen may develop eczema in response to cross-reacting foods such as green apple, carrots, hazelnut, celery, and pear [8990].

Alternatively, people already sensitized to some substances through skin contact may develop eczema after ingesting them. Common allergens include balsam of Peru (found in flavorings, spices, and certain foods), nickel (found in whole wheat bread, oatmeal, legumes, soy, shellfish, and processed meats), and propylene glycol (found in processed foods) [919293].

Avoiding the specific food trigger can help prevent the development or worsening of eczema, but only in people with a proven allergy [9495].

Vegetarian Diet/Quercetin

Quercetin is a plant antioxidant recognized as one of the best natural antihistamines. It may reduce allergic inflammation by inhibiting IL-33 [143319].

In a clinical trial of people with eczema (atopic dermatitis), a vegetarian diet improved the symptoms and reduced the levels of white blood cells (eosinophils and neutrophils). The authors of the study attributed the effects of this diet to its high content in flavonoids, especially quercetin [141142].

Supplementation with quercetin, as well as with a rich source of this flavonoid (dodder seed extract), improved contact and atopic dermatitis in two small trials [143144].

Food sources of this flavonoid include vegetables such as capers, onions, eggplant, celery, and asparagus, fruits such as berries, apples, and oranges, nuts, and tea (both green and black) [145].

Prebiotic Oligosaccharides

Feeding mice with prebiotic oligosaccharides reduced the levels of both IL-33 and IL1RL1 in lining tissues [320].

Prebiotics contain non-digestible ingredients that stimulate the development and activity of beneficial gut bacteria. A lot of them are oligosaccharides, a class of carbohydrates formed by a small number of sugar molecules [172].

In a few clinical trials, feeding newborns with formula containing galacto-oligosaccharides, fructo-oligosaccharides, or their combination prevented eczema during the first years of life and improved the symptoms in those already suffering from this condition [173174175176177178179180].

ID2

UV Light Therapy

Exposure to ultraviolet (UV) light increased ID2 activity in human cells in a laboratory setting [321].

Ultraviolet radiation has been extensively used for eczema, especially in severe cases. While UVA is more effective to improve flares (especially if combined with the photosensitizer psoralen), UVB is preferable to manage chronic eczema. Importantly, UVB is less likely than UVA to cause skin cancer [76777879].

UV radiation helps with eczema by inhibiting inflammation and the immune response, making the skin thicker, and killing potentially infectious skin bacteria [808182].

Probiotics

People with certain ID2 variants may have more difficulty regulating their gut microbiota than the average person. Broadly speaking, low ID2 activity has been linked to reduced defenses against gut infections, suggesting that the gut microbiota isn’t healthy. Researchers attribute this difference in part to ID2 and its ability to regulate gut microbes [322].

A healthier and more balanced gut flora may be achieved by supplementing with probiotics. In people with eczema, different probiotic strains slightly improved skin inflammation. The most common Lactobacillus species tested include L. rhamnosusL.reuteriL. plantarumL. paracaseiL. fermentum, and L. sakei [34567879].

Bifidobacterium species such as B. animalisB. breve, and B. longum have been mainly tested in combination with Lactobacillus strains. The studies produced mixed results, possibly due to differences in the strains used [31011121314].

Preventive prenatal maternal or postnatal pediatric supplementation with combinations of some of these Lactobacillus and Bifidobacterium strains in families with a history of atopic disease significantly lowered the incidence of eczema in children [15164171819202021222324].

Cannabidiol (CBD)

Cannabidiol (CBD) stimulated ID2 production in a cell-based study [323].

In a small trial on people with eczema and other skin conditions, an ointment containing CBD (without THC) improved the symptoms and skin parameters such as hydration, barrier function, and elasticity [69].

The anti-inflammatory effects of CBD in a cell-based study suggest it may also help with allergic dermatitis [70].

IRF4

Sunlight Exposure/Vitamin D

Vitamin D appears to directly inhibit IRF4 gene expression, according to a handful of cell studies. The vitamin D receptor VDR can also bind to a region of DNA that alters the expression of the IRF4 gene [324].

Studies have associated low blood vitamin D levels with eczema (atopic dermatitis) in children. In people with food sensitization, those with the lowest vitamin D levels had more severe eczema [36373839].

A healthy exposure to sunlight is the best way of increasing your blood vitamin D levels. In addition, you can eat food sources of this vitamin (such as fatty fish, liver, egg yolks, and dairy) [40].

Research also suggests that vitamin D supplementation can improve eczema severity, although some studies found it ineffective [37414243].

Avoiding Cigarette Smoke

Cigarette smoke is believed to have a complex interaction with STAT3 that may lead to increased IRF4 levels and greater rates of cell death [325326].

A meta-analysis of studies associated both mild and extensive exposure to cigarette smoke (especially by actively smoking) with an increased incidence of eczema (atopic dermatitis). Cigarette smoke is believed to impair the skin barrier function and alter the immune system [236].

HLA

Sunlight Exposure/Vitamin D

Some research suggests that UV light and vitamin D help control the immune response by suppressing HLA proteins [327328329330].

Studies have associated low blood vitamin D levels with eczema (atopic dermatitis) in children. In people with food sensitization, those with the lowest vitamin D levels had more severe eczema [36373839].

A healthy exposure to sunlight is the best way of increasing your blood vitamin D levels. In addition, you can eat food sources of this vitamin (such as fatty fish, liver, egg yolks, and dairy) [40].

Research also suggests that vitamin D supplementation can improve eczema severity, although some studies found it ineffective [37414243].

Avoiding Cigarette Smoke

Smoking may increase HLA activity in immune cells [331].

A meta-analysis of studies associated both mild and extensive exposure to cigarette smoke (especially by actively smoking) with an increased incidence of eczema (atopic dermatitis). Cigarette smoke is believed to impair the skin barrier function and alter the immune system [236].

Black Seed

The active ingredient of black seed, thymoquinone, may reduce HLA activity in immune cells [332].

One review of 4 studies concluded that oral black seed oil may help with allergic symptoms, including eczema, when used as an add-on to conventional therapy [182].

Niacinamide

In skin cells, niacinamide blocked the induction of HLA activity in response to cytokines (TNF-alpha and IFN-gamma) [333].

Niacinamide 2% cream reduced skin water loss and improved skin hydration in patients with atopic dermatitis when applied 2x/day for 2 months [160].

In people with facial seborrheic dermatitis, niacinamide 4% cream reduced symptoms such as redness and scaling by 75% after 3 months [161].

Green Tea (EGCG)

Green tea’s active component epigallocatechin gallate (EGCG) has been shown to block HLA activity in T cells [334].

In breast cancer patients with dermatitis caused by radiation therapy, topical EGCG application reduced pain, burning, itching, pulling, and tenderness [288].

Similarly, a cream with EGCG, grape seed procyanidins, and vitamin E improved eczema (atopic dermatitis) in a preliminary clinical trial [289].

Probiotics

In two studies of people with multiple sclerosis and HIV infection, probiotics containing different Lactobacillus and Bifidobacterium strains reduced HLA activity [335336].

In people with eczema, different probiotic strains slightly improved skin inflammation. The most common Lactobacillus species tested include L. rhamnosusL.reuteriL. plantarumL. paracaseiL. fermentum, and L. sakei [34567879].

Bifidobacterium species such as B. animalisB. breve, and B. longum have been mainly tested in combination with Lactobacillus strains. The studies produced mixed results, possibly due to differences in the strains used [31011121314].

Preventive prenatal maternal or postnatal pediatric supplementation with combinations of some of these Lactobacillus and Bifidobacterium strains in families with a history of atopic disease significantly lowered the incidence of eczema in children [15164171819202021222324].

Thunder God Vine

Active components isolated from thunder god vine reduced HLA levels in antigen-presenting cells (dendritic cells) [337338].

A meta-analysis of 13 clinical trials found thunder god vine effective at treating eczema, especially in combination with conventional medication. However, the authors warned about its potential adverse effects and the small size of most studies [210].

MYC

Sunlight Exposure/Vitamin D

Vitamin D appears to reduce c-myc activity. Once activated, the vitamin D receptor VDR can bind to a region of DNA that lowers the expression of the MYC gene. Sunlight and vitamin D have been studied for their potential to suppress some types of cancer for that reason, but this action may also benefit people with allergies [339].

Studies have associated low blood vitamin D levels with eczema (atopic dermatitis) in children. In people with food sensitization, those with the lowest vitamin D levels had more severe eczema [36373839].

A healthy exposure to sunlight is the best way of increasing your blood vitamin D levels. In addition, you can eat food sources of this vitamin (such as fatty fish, liver, egg yolks, and dairy) [40].

Research also suggests that vitamin D supplementation can improve eczema severity, although some studies found it ineffective [37414243].

Black Seed

Thymoquinone, an active compound found in black seed oil, reduced c-myc activity in mice [340].

In a clinical trial of people with hand eczema, topical black seed oil improved the symptoms as effectively as the corticosteroid betamethasone [100].

In breast cancer patients, a gel with 5% black seed oil reduced the severity and delayed the onset of radiation dermatitis [101].

IL6R

Reducing Stress

Acute stress increases the blood levels of IL-6 and other inflammatory cytokines according to a meta-analysis of 33 human studies. Similarly, chronic stress induced a persistent state of mild inflammation characterized by high levels of this and other cytokines [341342].

A meta-analysis concluded that psychological interventions aimed at reducing stress may improve eczema severity, itching intensity, and scratching [111].

We recommend addressing sources of stress in your life, either by taking up a stress-busting hobby (such as yoga or meditation) or seeking professional help.

Acupuncture

In rats with eczema, acupuncture improved skin inflammation by lowering the levels of IL-6 and other inflammatory mediators [118343].

A meta-analysis of 8 studies found acupuncture effective at reducing the symptoms and severity of eczema. However, the authors warned that all the studies compared acupuncture with no treatment or with conventional medication instead of using a more suitable negative control (“sham” or fake acupuncture) [50].

Fermented Foods

A study of Japanese men associated the intake of fermented soybean products with lower IL-6 levels. Similarly, fermented soybean products reduced the levels of this cytokine and improved skin inflammation in mice [344345].

In adults, diets rich in fermented foods such as kimchi, fermented seafood, and pickled have been associated with a reduced incidence of eczema. In children, the intake of yogurt showed similarly protective effects [132133134135].

In a clinical trial, orange juice fermented with a Lactobacillus plantarum strain improved the symptoms and quality of life in people with mild to moderate eczema [6].

The intake of fermented foods such as yogurt and natto by pregnant women helped prevent eczema in their children during their first 2 years of life. However, a study suggests that other fermented foods such as miso soup eaten during breastfeeding may have the opposite effects and should be avoided [136137138].

In some cases, fermented foods may help by providing beneficial microorganisms. Other foods don’t contain alive microorganisms (e.g., if they have been heat-killed) but supply the beneficial metabolites produced during the fermentation process [132].

Vegetarian Diet/Quercetin

In mice with eczema and psoriasis, supplementation with quercetin improved skin inflammation and reduced the levels of IL-6 and other inflammatory mediators [139346].

In a clinical trial of people with eczema (atopic dermatitis), a vegetarian diet improved the symptoms and reduced the levels of white blood cells (eosinophils and neutrophils). The authors of the study attributed the effects of this diet to its high content in flavonoids, especially quercetin [141142].

Supplementation with quercetin, as well as with a rich source of this flavonoid (dodder seed extract), improved contact and atopic dermatitis in two small trials [143144].

Food sources of this flavonoid include vegetables such as capers, onions, eggplant, celery, and asparagus, fruits such as berries, apples, and oranges, nuts, and tea (both green and black) [145].

Zinc

In cells, treatment with zinc was found to reduce levels of IL-6 [347].

Zinc deficiency (determined as low zinc levels in the blood and hair) was associated with increased odds of eczema (atopic dermatitis) in a meta-analysis. However, the authors warned about the low quality of most included studies [245].

Good dietary sources of zinc include red meat, seafood, dairy products, nuts, legumes, and whole grains [246].

Licorice

Several active components isolated from licorice reduced skin inflammation and lowered IL-6 levels in animal and cell-based studies [158348267349350].

A gel with 1-2% of licorice root reduced skin redness, itching, and swelling in people with eczema. A different herbal formulation with licorice root, willow bark, and gentian root extracts had anti-inflammatory effects comparable to those of hydrocortisone in another study [5960].

Similarly, formulations containing licorice’s active compound licochalcone A, applied on the face, forearms, and scalp, improved skin itching, inflammation, redness, and dryness as effectively as hydrocortisone [616263646566].

Borage Oil

Borage oil reduced IL-6 levels in mice and skin cells exposed to UVB radiation [351].

Borage oil contains high levels of omega-6 fatty acids (such as gamma linolenic acid) that are vital to the proper structure and function of the skin barrier [26].

In a few studies of children with seborrheic dermatitis, topical borage oil improved the symptoms within 1-3 weeks [272829].

Tea Tree Oil

Tea tree oil lowered the levels of IL-6 and other pro-inflammatory cytokines in several cell-based studies [352353354].

In people with nickel hypersensitivity, tea tree oil has been reported to reduce the area and redness of eczema [355356].

A shampoo with 5% tea tree oil reduced dandruff severity and itching in people with seborrheic dermatitis [357].

Aloe Vera

In mice and skin cells, aloe vera reduced inflammation in part by reducing IL-6 levels [358359360].

A gel with aloe vera among other ingredients was effective at improving mild to moderate seborrheic dermatitis in a small trial [253].

Aloe vera improved diaper rash in another study, although marigold ointment was more effective [254].

Examination gloves delivering aloe vera improved skin integrity and reduced wrinkles and redness in people with contact dermatitis [255].

Niacinamide

In skin cells, niacinamide reduced inflammation by lowering the levels of IL-6 and other inflammatory mediators [361362].

Niacinamide 2% cream reduced skin water loss and improved skin hydration in patients with atopic dermatitis when applied 2x/day for 2 months [160].

In people with facial seborrheic dermatitis, niacinamide 4% cream reduced symptoms such as redness and scaling by 75% after 3 months [161].

Emu Oil

Emu oil reduced the levels of IL-6 and other pro-inflammatory cytokines in skin cells (fibroblasts) [363].

In a month-long clinical trial, twice-daily application of 20% emu oil improved the redness, itching, and scales associated with seborrheic dermatitis. However, it was not as effective as the popular treatment hydrocortisone [364].

In breast cancer patients, emu oil reduced dermatitis caused by radiation therapy [365].

Coconut Oil

Virgin coconut oil had anti-inflammatory effects, in part by lowering IL-6 levels, in skin cells [31].

Virgin coconut oil, applied daily for eight weeks, was an effective treatment for mild to moderate atopic dermatitis (eczema) in a clinical trial [32].

Coconut oil has also been reported to moisturize the skin and prevent infections, which may further help improve eczema [3334].

Echinacea

In a small trial of people with eczema, applying a cream with echinacea for 3 months helped improve skin redness, swelling, and barrier function. Its active components blocked IL-6 production in skin cells [73].

Probiotics

Saccharomyces boulardii has been found to decrease levels of IL-6 and reduce inflammation in human cells [366].

In people with eczema, supplementation with different probiotic strains slightly improved skin inflammation. The most common Lactobacillus species tested include L. rhamnosusL.reuteriL. plantarumL. paracaseiL. fermentum, and L. sakei [34567879].

Bifidobacterium species such as B. animalisB. breve, and B. longum have been mainly tested in combination with Lactobacillus strains. The studies produced mixed results, possibly due to differences in the strains used [31011121314].

Preventive prenatal maternal or postnatal pediatric supplementation with combinations of some of these Lactobacillus and Bifidobacterium strains in families with a history of atopic disease significantly lowered the incidence of eczema in children [15164171819202021222324].

Prebiotic Oligosaccharides

In mice with eczema, supplementation with different prebiotic oligosaccharides improved skin inflammation and blocked the production of IL-6 and other cytokines [367170].

Prebiotics contain non-digestible ingredients that stimulate the development and activity of beneficial gut bacteria. A lot of them are oligosaccharides, a class of carbohydrates formed by a small number of sugar molecules [172].

In a few clinical trials, feeding newborns with formula containing galacto-oligosaccharides, fructo-oligosaccharides, or their combination prevented eczema during the first years of life and improved the symptoms in those already suffering from this condition [173174175176177178179180].

Melatonin

In animal and cell-based studies, formulations with melatonin reduced skin inflammation in response to UV radiation in part by reducing IL-6 levels [368369370].

Melatonin supplementation improved both disease severity and sleep disturbances in 2 clinical trials on children with eczema [184185].


About the Author: Carlos Tello
PHD (MOLECULAR BIOLOGY)
Carlos received his PhD and MS from the Universidad de Sevilla.
Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.



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