Antioxidants for Psoriasis

Overview of Psoriasis

Psoriasis is a chronic, inflammatory, cell-mediated skin disease that affects 2-3% of the world’s population.^[1] It most commonly involves the skin, but can also affect the joints, bones, and nails. It is commonly characterized by thickened plaques of skin with silvery scales.

Etiology

The exact etiology of psoriasis is largely unknown. However, it is generally accepted to be an autoimmune condition mediated by T lymphocytes. There are many factors that can influence and exacerbate the onset and progression of psoriasis.^[2]

• Genetics: psoriasis is often seen among families, suggesting that there may be a genetic component.
• Trauma: various forms of injury to the skin, such as mechanical, chemical, and radiation can provoke the onset of psoriatic lesions.
• Medications: various medications have been associated with increasing the severity of psoriasis, such as chloroquine, lithium, beta-blockers, steroids, and NSAIDs.
• Climate: warmer climates and seasons have been associated with improved symptoms, whereas winter may contribute to worsening symptoms in psoriasis.

Additionally, there are a variety of other factors that may also impact the severity of psoriasis, such as stress, infections, environment, tobacco use, alcohol, and obesity.^[2]

Epidemiology

The onset of psoriasis can occur at any age. However, a bimodal age distribution has been observed, with the first age peak ranging from 16 to 22 years old, and a second peak ranging from 57 to 60 years old.^[2,3]

Psoriasis affects approximately 125 million individuals globally. While psoriasis can affect anyone, studies have shown that there is an increased prevalence in countries located at higher latitudes, such as the United States and Norway. Whereas countries at lower latitudes that are closer to the equator, such as certain African and Asian countries, have lower rates of psoriasis.^[4]

Interestingly, other autoimmune disorders also present in a similar global distribution. This phenomenon is referred to as the ‘equator effect’ and is generally not well understood. It is thought to be due to both genetics and environmental factors such as vitamin D exposure.^[4]

Presentation

The most common clinical manifestation of psoriasis is cutaneous lesions or plaques. Psoriatic lesions can be further classified into plaque, guttate, pustular, and erythrodermic types according to clinical features. The most common type of psoriasis is described as “vulgaris” or plaque psoriasis, which is characterized as erythematous (red), round lesions covered with silvery scales on the extensors of extremities (elbows, knees, scalp, and back).^[2]

Additionally, the nail can also be affected in psoriasis. This may appear as a white area within the nail plate (leukonychia), splitting of the nail (onycholysis), and nail pitting.

The extent of psoriasis can be quite severe. The Psoriasis Area and Severity Index (PASI) is used to measure and quantify disease progression and severity. It specifically assesses the intensity (redness, thickness, scaling) and affected body surface area to yield a score. The scoring ranges from 0 (no disease) to 72 (maximal disease).

Pathophysiology

Psoriatic plaques arise due to increased skin cell (keratinocyte) proliferation with incomplete epidermal keratinocyte differentiation and decreased keratinocyte cell death (apoptosis).^[2] This is thought to be caused by increased T cell infiltration that stimulates the overproduction of skin cells. The increased skin growth and lack of cell death lead to the thickened areas of skin that are commonly associated with psoriasis. Additionally, psoriatic skin cells fail to secrete lipids which results in the skin becoming dry and flaky, another common characteristic of psoriasis.^[2]

In general, the pathogenesis of psoriasis is multifactorial and dynamic. In fact, the etiology is still largely unknown. However, in addition to many other factors, studies suggest that psoriasis may be the result of oxidative stress. There are many prescription treatment options that target different purposed pathways of psoriasis formation, with antioxidant supplementation being a new and emerging field of research as a psoriasis treatment and adjunctive therapy.

Redox Homeostasis

A delicate balance exists between reactive oxygen species (ROS) and antioxidants. When ROS exceeds the activity of antioxidants, the body can enter a state of oxidative stress.

Reactive oxygen species

Reactive oxygen species (ROS), also referred to as free radicals, are chemically reactive compounds that contain oxygen. These are formed as by-products of cellular metabolism, as well as from radiation exposure and environmental pollutants.^[5] Examples include superoxide anion (O₂⁻), hydroxyl radical (HO⁻), hydrogen peroxide (H₂O₂), and peroxynitrite (ONOO⁻).^[1]

Overproduction or lack of ROS neutralization can cause DNA damage, lipid peroxidation, and production of inflammatory cytokines.^[6] Excess free radicals have the potential to cause significant cellular damage and may play an influential role in the pathogenesis of psoriasis.

Antioxidants

Free radicals are normally neutralized by antioxidants in the body. This process is considered an endogenous defense mechanism against ROS. Antioxidants involved in this process include a variety of enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, thioredoxins, and peroxiredoxins.^[1,5]

Not only are antioxidants naturally produced in the body, but a variety of fruits and vegetables also contain antioxidants that can eliminate free radicals. Nutrient-derived antioxidants include vitamin E, vitamin C, carotenes, flavonoids, glutathione, uric acid, and taurine.^[5]

Oxidative stress

When there is an abundance of ROS and not enough antioxidants to help neutralize the free radicals, it can cause significant damage to macromolecules such as lipids, proteins, and DNA.^[1] This is referred to as oxidative stress. Progressive damage to cells from oxidative stress has been associated with the pathogenesis of many human diseases, including psoriasis.^[1]

Oxidative Stress in Psoriasis

An abundance of free radicals and a deficiency in the quantity and activity of antioxidants can induce a state of oxidative stress in the body. Oxidative stress has the potential to play a pathogenic role in a variety of inflammatory conditions, including psoriasis. 

Many studies have shown that redox imbalances are present in blood and skin samples of individuals with psoriasis.

• Elevated oxidative stress markers: malondialdehyde (MDA), lipid hydroperoxides, thiobarbituric acid-reactive substances, protein carbonyl, nitric oxide, and erythrocyte MDA.^[1] In tissue samples, malondialdehyde, a byproduct of lipid peroxidation from oxidative stress, is also elevated in individuals with psoriasis.^[7,8]
• Decreased endogenous antioxidants: total blood thiols, serum vitamin E, superoxide dismutase (in erythrocytes, serum, and plasma), catalase (serum and plasma), serum paraoxonase-1, and erythrocyte GSH peroxidase (GSH-px).^[1]

Interestingly, ROS serves as a secondary messenger in response to oxidative stress. By signaling downstream pathways, specifically mitogen-activated protein kinases/activator protein-1(MAPK/AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Janus kinase-signal transducer and activator of transcription (JAK–STAT), excess ROS can effectively induce the production of inflammatory mediators, cytokines, and growth factors.^[1,6]

The activation of and increase in pro-inflammatory products in response to cellular damage from oxidative stress, coupled with a decreased abundance and activity of endogenous antioxidants, is thought to be one of the key players in the pathophysiology of psoriasis.^[1,9]

Antioxidants for Psoriasis

Psoriasis is associated with a decrease in antioxidants and an increase in oxidative stress markers. This imbalance creates an inflammatory reaction that stimulates the immune system. An overactive immune system is one of the contributing factors that causes and exacerbates psoriasis.^[1]

In an attempt to mediate this imbalance, studies have begun looking at antioxidant supplementation as a complementary treatment for psoriasis. Such treatments include various plant compounds, amino acids, and trace elements.

Curcumin

Curcumin is a polyphenol compound derived from the root of the turmeric plant, also known as Curcuma longa from the Zingiberaceae family.^[10] Turmeric is commonly used as a cooking spice, and curcumin extracts from the plant are used as pigmentary agents in make-up, as well as herbal supplements to treat a variety of inflammatory conditions, such as psoriasis.

Curcumin has been shown to possess a variety of beneficial properties, such as antioxidant, anti-inflammatory, anti-proliferative, anti-carcinogenic, and anti-microbial properties, which has made it a popular compound for a variety of health conditions.^[10]

The antioxidant properties of curcumin have been thought to play a role in reducing oxidative stress in psoriasis. In recent years, there have been several studies that support the anti-inflammatory effects of curcumin in the treatment of psoriasis.

• Inhibition of the activity of phosphorylase kinases, which is found to be elevated in individuals with psoriasis and contributes to increased cell proliferation.^[10,11]
• Reduction in inflammation by downregulating proinflammatory cytokines (ILK-17, ILK-6 TNF- α, INF- γ).^[12]
• Upregulation of involucrin and filaggrin which serves to improve the barrier function of the skin.^[12]

Additionally, curcumin has not been shown to have any significant side effects. In fact, the U.S. Food and Drug Administration (FDA) has defined curcumin as “generally regarded as safe” (GRAS).^[10]

Dimethyl fumarate

Fumaric acid esters (FAEs) have been used for the treatment of psoriasis for over 20 years in several European countries. The active ingredient in FAEs is dimethyl fumarate (DMF), which is named after the “earth smoke plant”, Fumaria officionalis.

The use of DMF is thought to be effective in reducing inflammation associated with psoriasis by influencing the antioxidant response pathway.

• Reduction in inflammatory cytokine production by shifting proinflammatory cytokines (T helper 1 and T helper 17) to anti-inflammatory cytokines (T helper 2).^[13]
• Normalization of keratinocyte hyperproliferation yielding a reduction in epidermal thickness.

A study of fifty individuals with psoriasis treated with FAEs showed a decrease in proinflammatory cytokines (IL-1β, IL-22, IL-36α, and IL-36γ) and an upregulation of the anti-inflammatory cytokine IL-37.^[13] Additionally, individuals treated with DMF reported improvements with body surface involvement and improved quality of life. This was reflected in the mean reduction of the Psoriasis Area and Severity Index (PASI) by 55%.^[13]

Additionally, treatment with DMF for psoriasis has been shown to have comparable effects to first-generation, anti-TNF-α biologics and is not associated with significant side effects.^[1,13] Therefore, the use of DMF for psoriasis may be a safe and effective alternative or adjunct therapy for psoriasis.

Cysteine

Glutathione (GSH) is a powerful endogenous antioxidant that helps protect the body from oxidative stress. It is a peptide consisting of three amino acids: glycine, glutamate, and cysteine. Cysteine is responsible for both the production of GSH and acting as the primary site for redox reactions within GSH molecules. A deficiency in cysteine can cause increased oxidative stress due to decreased levels and activity of GSH.^[14]

Interestingly, individuals with psoriasis have been shown to have lower levels of GSH, which may be responsible for increased oxidative stress commonly associated with psoriasis.^[14] Oral GSH supplementation has not been found to be effective at increasing GSH levels. However, supplementation of GSH precursors, such as cysteine, have better outcomes of increasing GSH.

A nonprescription, bioactive, whey protein supplement called Immunocal (Immunotec Inc.), has been shown to increase endogenous GSH production by delivering proteins high in cysteine and cysteine residues that are not susceptible to denaturing. In fact, a study of seven individuals with psoriasis who consumed 20g of Immunocal a day for three months in addition to their current treatment regime, if any treatment at all, noted improvement of PASI scores.^[14]

In this study, researchers concluded that the PASI score may have improved over time from concurrent medication therapies; However, the PASI scores also showed improvement in individuals who were not currently taking medications or receiving additional psoriasis treatments.^[14] This evidence suggests that supplementation of cysteine has the potential to reduce oxidative stress associated with psoriasis by stimulating GSH production. It should be noted that this study used a very small population size, and further studies involving a larger cohort are needed to evaluate the efficacy of Immunocal or other GSH precursors for the treatment of psoriasis.

Mustard seed

Sinapis Alba Linn, more commonly known as mustard seed, is a popular cooking spice that belongs to the Brassica Family. Mustard seed has been used for centuries in Chinese medicine to help promote breathing, eliminate respiratory infections and relieve pain.^[15] Recently, it has been studied for its anti-inflammatory properties and potential use in the treatment of psoriasis.^[15]

In this study, mouse models were used to study the effects of mustard seed on psoriasis. In order to reproduce a similar disease state of psoriasis a topical immunomodulator, Imiquimod (IMQ), was applied to the mice. IMQ can effectively induce an inflammatory response in an otherwise healthy body by releasing IFN-α. In patients with psoriasis, the effect is amplified, and exposure to IMQ can severely exacerbate or induce psoriatic lesions.^[15]

After consumption of food containing 5% mustard seed, researchers found that mustard seed could increase endogenous antioxidant activity (SOD, catalase, and GSHpx) and reduce inflammatory cytokines (NF‐κB, IFN‐α, IL‐17, and IL‐22). Additionally, there was a reduction in the PASI score of mice who were given mustard seed.^[15]

This data suggests that mustard seed may play a role in mitigating oxidative stress, and is deserving of further research as a potential treatment for psoriasis. 

Selenium

Selenium (Se) is a natural trace element that has been shown to possess both immune-modulating and antiproliferative properties in humans.^[16] Studies have shown that selenium can make immune cells more resistant to oxidative stress by altering the expression of cytokines and their specific receptors, and thus mitigating the inflammatory response associated with psoriasis.

Individuals with psoriasis have been shown to have lower concentrations of selenium compared to healthy individuals without a history of psoriasis.^[16] When supplemented with selenium, studies have shown that TNF-α (proinflammatory cytokine) levels were suppressed. In fact, the suppression of TNF-α is one of the main pathways in which biologic medications function to treat psoriasis.

A double-blind, placebo-controlled clinical study involving fifty-eight individuals with psoriasis compared the effects of an antioxidant complex containing selenium aspartate, coenzyme Q10, and Vitamin E versus a placebo on psoriasis. They found that the individuals who were supplemented with the antioxidants showed significant improvement of psoriasis by PASI and Severity Score (SS). These results are thought to have occurred due to the observed reduction in oxidative stress exerted by the effects of the antioxidants.^[17]

This study suggests that the lack of TNF-α inhibition from a selenium deficiency in addition to reduced antioxidant levels and activity may be another contributing factor to the pathogenesis of psoriasis. However, studies on Selenium and psoriasis are scarce and more research is needed.

Alga Dunaliella bardawil

Dunaliella bardawil is a green alga that naturally contains 9-cis β-carotene, a retinoid precursor.^[18] Systemic retinoid therapy has been used for many years as an effective treatment for psoriasis, however, it is associated with elevated liver enzymes, elevated plasma triglycerides, and increased low-density lipoprotein (LDL) cholesterol, which requires close monitoring. Therefore, an alternative retinoid treatment with a better safety profile may be a more appealing treatment option for psoriasis.

A randomized, double-blind, placebo-controlled study of thirty-four individuals with mild, chronic plaque psoriasis was performed to assess the antioxidant effects of Dunaliella bardawil on psoriasis. After six weeks, the PASI was significantly reduced in comparison to the control group (61.3% vs 34%, respectively).^[18] Additionally, unlike other retinoids, Dunaliella bardawil did not demonstrate adverse effects on liver function or lipid profile.^[18]

Although alga Dunaliella bardawil does not function as an antioxidant, it may be a safe and effective treatment alternative to systemic retinoid therapies. This research is a promising treatment option for psoriasis, however, larger studies are warranted.

Fruits and vegetables

All fruits and vegetables naturally contain a range of antioxidants, such as carotenoids, flavonoids and vitamin C that are known to reduce oxidative stress in the body. Examples of foods that are especially rich in antioxidants include berries, grapes, nuts, dark green vegetables, whole grains, orange-colored fruits and vegetables, and green tea.

Increasing dietary antioxidants may help reduced oxidative stress associated with psoriasis. Although there aren’t specific studies solely on the effects of fruit and vegetable consumption on psoriasis, it should not be overlooked as an adjunctive therapy in the treatment of psoriasis.^[19]

Key Takeaways

• Antioxidant deficiencies can induce oxidative stress and induce or worsen psoriasis.
• Consuming a diet rich in fruits and vegetables may be beneficial in psoriasis treatment due to the natural abundance of antioxidants.
• Always consult with your healthcare provider before adding antioxidant supplements into your psoriasis treatment regime.