A thorough review and analysis of the medical literature found that fish oil supplementation is beneficial in psoriasis. Fish oil supplements (up to 13.5 g eicosapentaenoic acid [EPA] and 9 g docosahexaenoic acid [DHA] daily) given to psoriasis patients for up to six months resulted in clinical improvement in skin redness, hardening, and scaling, and some studies found a benefit for itching (Millsop 2014).
Fish oil may also be effective as a complement to other therapies. In one study in patients with plaque psoriasis, the combination of omega-3 fatty acids and tacalcitol, a topical form of vitamin D, resulted in significantly greater improvement than tacalcitol alone (Balbas 2011).
Fish oil is well-known for its potent anti-inflammatory properties. Elevated concentrations of the pro-inflammatory omega-6 fatty acid arachidonic acid and inflammatory compound leukotriene B4, derived from arachidonic acid, have been found in the skin and red blood cell membranes of psoriasis patients. By displacing arachidonic acid in cell membranes, the omega-3 fatty acids EPA and DHA suppress inflammation by inhibiting the production of pro-inflammatory compounds such as leukotriene B4 (Surette 2008; Millsop 2014; Balbas 2011; Wolters 2005).
While topical synthetic forms of vitamin D (analogs) are used in the conventional treatment of psoriasis, multiple studies have demonstrated that the natural form of vitamin D3 (cholecalciferol), which can be taken orally, may be a safe and effective psoriasis treatment (Kim 2010; Finamor 2013; Millsop 2014).
Oral vitamin D has the important advantage of improving vitamin D status, which results in many health benefits (Higdon 2014b). A number of studies have shown that psoriasis is associated with low serum levels of 25-hydroxyvitamin D. Vitamin D acts as an immune-modulating hormone that can reduce rapid growth of skin cells and suppress inflammation. Higher levels of vitamin D are associated with lower risk of cardiovascular disease, diabetes, and metabolic syndrome—all associated with psoriasis (Chandrashekar 2015; Soleymani 2015; Hossein-nezhad 2013; Gisondi 2012; Vitezova 2015).
In a 2013 study, psoriasis symptoms significantly improved in patients receiving high daily doses of vitamin D3 (35 000 IU) for six months in combination with a low-calcium diet and aggressive hydration. Blood chemistry parameters remained within the normal range; the authors explained that restriction of dietary calcium likely played a key role in avoiding excess calcium levels in this trial of high dose vitamin D. Nevertheless, 35 000 IU is a much higher-than-usual daily dose of vitamin D, and anyone high-dose vitamin D should test their blood levels of 25-hydroxyvitamin D regularly and adjust their dosage as necessary to avoid excessive levels.
The high doses of vitamin D used in this study may have compensated for genetic variations (polymorphisms) related to vitamin D metabolism that are common in autoimmune conditions such as psoriasis. These inherited polymorphisms induce a relative resistance to vitamin D, necessitating higher doses to achieve optimal biologic effects (Finamor 2013).
Indeed, experimental research has shown that genetic variation in activity of 1-alpha-hydroxylase, the enzyme that converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (the active form), strongly influences serum levels of active vitamin D (Vieth 1990). In fact, specific 1-alpha-hydroxylase mutations can cause vitamin D-specific rickets (Miller 2000). In mice prone to autoimmunity, upregulation of 1-alpha-hydroxylase activity in response to immune stimuli is dysfunctional. It has been proposed that 1-alpha-hydroxylase activity upregulation in immune cells during inflammatory stimuli serves as a guard against autoimmunity (Overbergh 2000). Thus, one factor contributing to autoimmune diseases could be defective 1-alpha-hydroxylase activity; taking high doses of vitamin D may help overcome this defect by providing abundant substrate upon which the suboptimally functioning 1-alpha-hydroxylase can act (Overbergh 2000).
Pycnogenol is an extract from the bark of the French maritime pine tree. It contains a range of polyphenolic compounds including proanthocyanidins, bioflavonoids, and catechins. Pycnogenol has strong anti-inflammatory, anticlotting, and vasodilating properties (Belcaro 2013; Gulati 2015; Belcaro 2014; Grether-Beck 2016).
In a placebo-controlled clinical trial in psoriasis patients, the addition of 50 mg of pycnogenol three times daily to standard treatment resulted in significant improvement in skin redness, hardening, and scaling compared with standard treatment alone (Belcaro 2014).
Studies have also demonstrated that pycnogenol has beneficial effects in metabolic syndrome, which occurs frequently in patients with psoriasis (Gulati 2015; Belcaro 2013; Siegel 2013; Girolomoni 2009).
Polypodium leucotomos is a tropical fern native to Central and South America where it has a long history of use as an herbal medicine for the treatment of inflammatory skin diseases. Polypodium leucotomos extract can help protect the skin from harmful effects of ultraviolet radiation, and can decrease the phototoxicity, pigmentation, and damage of human skin induced by PUVA (psoralen combined with UVA radiation) treatment. Because it also decreases DNA damage and immunosuppression induced by UV radiation, Polypodium leucotomos can slow premature skin aging and reduce the risk of skin cancers (Middelkamp-Hup 2004; Palomino 2015; Choudhry 2014).
While phototherapy—particularly PUVA—is a very effective treatment for psoriasis, it carries the risk of skin cancers, including melanoma. The photoprotective effects of Polypodium leucotomos make it a potential adjuvant to phototherapy used for psoriasis (Stern 2001; Nettelblad 1996; Middelkamp-Hup 2004; Gonzalez 2011; Palomino 2015; Choudhry 2014).
Peony glucosides are extracted from the root of the peony plant, and have been shown to help restore immune system balance by decreasing the production of inflammatory cytokines. The peony plant has been widely used in traditional Asian medicine to treat autoimmune diseases (He 2011; Wang, Zhang 2014).
Findings from a 2014 study demonstrate potential benefits of peony glucosides in the treatment of psoriatic arthritis. Substantial clinical improvement, along with a significant drop in inflammatory cytokines, was observed in 32% of patients treated exclusively with peony glucosides. These results merit further investigation of peony glucosides as a safe and effective therapy for psoriatic arthritis (Wang, Zhang 2014).
The spice turmeric has been used as an herbal remedy in traditional Chinese and Ayurvedic medicine for thousands of years. Curcumin is generally considered to be the most active constituent in turmeric. Owing to its anti-inflammatory properties as well as its ability to inhibit excessive new growth of cells and blood vessels, curcumin has promise as a potential therapy in the treatment of psoriasis (Chen 2008; McFadden 2015; Antiga 2015; Sun 2013; UMMC 2014b).
In a clinical study, a combination of oral curcumin and topical steroids was superior to topical steroids plus placebo in treating psoriasis. These results suggest curcumin can be a safe and effective adjuvant therapy in psoriasis patients treated with topical steroids (Antiga 2015).
The trillions of bacteria present in and on the human body, called the microbiota, have a pronounced effect on our immune system. They have a direct effect in the digestive tract and act systemically as well, affecting distant sites including the skin and joints (Eppinga 2014; Geuking 2014; Ferreira 2014).
An altered microbiota is a factor in the initiation and promotion of immune-mediated inflammatory diseases, including inflammatory bowel disease. Both psoriasis and psoriatic arthritis have been associated with inflammatory bowel disease. It has been suggested that the microbiota may play a key regulatory role in the inflammatory pathways shared by these diseases (Li, Han 2013; Eppinga 2014; Geuking 2014; Ferreira 2014). In fact, emerging evidence suggests psoriasis may not strictly involve autoimmunity, but could be the consequence of interaction between the innate immune system and some bacteria of the human microbiota (Fry 2015).
In a 2013 study, administration of a probiotic called Bifidobacterium infantis significantly reduced plasma levels of the inflammatory biomarkers C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) in psoriasis patients (Groeger 2013).
Psoriasis is marked by an increase in oxidative stress and a decrease in levels of glutathione, the body’s major scavenger of reactive free radicals. Whey protein effectively increases cellular glutathione levels because it is a rich source of the amino acid precursors of glutathione, particularly cysteine and related compounds (Prussick 2013; Kloek 2011; Balbis 2009; Zavorsky 2007).
In one study, administration of whey protein isolate over three months resulted in clinical improvement in patients with psoriasis, regardless of whether the whey protein was given alone or in addition to topical or light therapies (Prussick 2013).
Resveratrol is a polyphenol found primarily in grapes, red wine, Japanese knotweed, and some berries. It effectively modulates inflammation, cell proliferation, and new blood vessel formation (OSU 2015; Kjaer 2015; Borriello 2014).
Resveratrol significantly improved the severity of skin inflammation in a mouse model of psoriasis. Skin thickness, redness, and scaling were all reduced in the resveratrol-treated group compared with the control group. Resveratrol decreased the production of the inflammatory cytokines IL-17 and IL-23, both significant contributing factors in the formation of psoriatic plaque (Kjaer 2015).
The essential mineral zinc plays an important role in maintaining a healthy immune response. Zinc modulates production of inflammatory cytokines such as IL-2 and IL-6 (Foster 2012; OSU 2015). In a study in mice with induced psoriasis, injections of zinc into the abdominal cavity mitigated oxidative stress and caused a significant decrease in elevated serum levels of inflammatory IL-2 (Yin 2013).
According to one case report, supplementation with 50 mg zinc twice daily in a 67-year-old female with pustular psoriasis completely cleared skin lesions in 15 days. Zinc’s anti-inflammatory and immune-modulating effects may explain its therapeutic efficacy in this case (Verma 2012). However, 100 mg of supplemental zinc daily is a relatively high dose and may not be suitable for everyone.
Vitamin E and Selenium
Selenium, a cofactor for enzymes such as glutathione peroxidase, and vitamin E are important contributors to the body’s defenses against oxidative stress (NHMRC 2006). Concentrations of both vitamin E and selenium have been reported to be lower in psoriasis patients than in healthy subjects (Pujari 2014; Serwin 2003; Kharaeva 2009; Naziroglu 2012). Oral or topical administration of vitamin E and selenium may be beneficial in the treatment and prevention of psoriasis (Naziroglu 2012; Kokcam 1999).
In a double-blind placebo-controlled clinical trial in patients with erythrodermic psoriasis (a severe form of psoriasis that usually affects much of the body surface and causes marked inflammation and skin turnover) and psoriatic arthritis, supplementation with selenium and vitamin E, together with coenzyme Q10, resulted in significant clinical improvement in disease severity (Kharaeva 2009).
Supplementation with selenium (200 mcg as sodium selenite) and vitamin E (10 mg as alpha-tocopheryl succinate) was demonstrated to increase low levels of glutathione peroxidase in 50 patients with various skin disorders, including psoriasis (Juhlin 1982). In another study, a measure of glutathione activity in psoriasis patients drinking selenium-rich water was found to be 50% higher than in healthy participants consuming low-selenium water (Shani 1985).
Many vitamin E formulations consist only of alpha-tocopherol. But mounting evidence suggests that other members of the vitamin E family, especially gamma-tocopherol, may be particularly integral to vitamin E’s beneficial effects (Mathur 2015).
Levels of homocysteine—an independent risk factor for cardiovascular disease and possibly Alzheimer’s disease—are often elevated in patients with psoriasis (Morris 2003; McDonald 2012; Tobin 2011; Malerba 2006).
Some studies have reported that psoriasis patients have lower levels of the B vitamin folate, which is essential in the breakdown of homocysteine. In one case-control study in patients with chronic plaque psoriasis, high plasma homocysteine correlated with increased disease severity and low levels of folate (Malerba 2006). Another study found decreased blood folate levels and increased plasma homocysteine levels in psoriasis patients who underwent UVB phototherapy (Juzeniene 2010).
Melatonin is a neurohormone secreted by the pineal gland in the brain. It regulates the 24-hour circadian rhythm, sleep, and inflammatory and immune processes. As an oral supplement, melatonin has been shown to be helpful in various sleep disorders such as insomnia and jet lag (NIH 2015; Kartha 2014; Radogna 2010).
Nighttime levels of melatonin have been demonstrated to be significantly lower in psoriasis patients than in matched control subjects without psoriasis (Kartha 2014; Mozzanica 1988). Shift workers with disrupted sleep-wake patterns also have low nighttime melatonin levels, along with an increased risk of psoriasis (Kartha 2014; Li, Qureshi 2013; Mozzanica 1988; Patel 2007; Yosipovitch 2000).
Given its complex and critical role in regulating a wide range of physiological functions, melatonin is being actively investigated for its importance to the major inflammatory diseases associated with psoriasis, including cardiovascular disease, type 2 diabetes, metabolic syndrome, and cancer (Sharma 2015; Zamfir Chiru 2014; Goyal 2014; Bonnefont-Rousselot 2014; Navarro-Alarcon 2014; Dominguez-Rodriguez 2012; Radogna 2010; Reiter 2010).
Capsaicin is a pungent compound present in various hot peppers including red chili peppers, jalapeños, and habaneros. Topical creams containing capsaicin have a long history of use as pain-relieving agents (Bode 2011; Chrubasik 2010).
In a double-blind study in which capsaicin cream was applied to only one side of the bodies of psoriasis patients, a significant reduction in scaling and redness was observed on the side of capsaicin application. While nearly half of the patients reported burning, stinging, itching, and redness upon initial application, these symptoms diminished or disappeared with continued treatment. The ability of capsaicin to inhibit dilation of blood vessels in the skin may have played a role in the therapeutic benefit (Bernstein 1986).
In another study in patients with pruritic (itchy) psoriasis, topically applied capsaicin was shown to significantly reduce itching and overall disease severity (Ellis 1993; Andoh 2003; Boca 2014).
Commonly known as frankincense, Boswellia serrata gum resin extracts have been used in traditional Ayurvedic medicine, and are now being investigated and used for the treatment of chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Boswellic acids, the active components of the Boswellia serrata resin, exert anti-inflammatory effects primarily through inhibition of the proinflammatory enzyme 5-lipoxygenase (5-LOX) (Togni 2014; Wang 2009).
Topical Boswellia extracts may be promising for the treatment of psoriasis. In a double-blind placebo-controlled study, a topical formulation based on boswellic acids was shown to be effective in the treatment of psoriasis. Specifically, the boswellic acid formulation improved scales in 70% of subjects and skin reddening in 60% of subjects. None of the participants experienced an exacerbation of their condition (Togni 2014).
Previously, in a mouse model of psoriasis, a boswellic acid (3-O-acetyl-11-keto-beta-boswellic acid, or AKBA) injected systemically or under the skin, inhibited nuclear factor-kappa B (NF-ĸB)—a signaling molecule implicated in exacerbating psoriasis. This resulted in markedly decreased production of inflammatory cytokines such as TNF-α, along with a profound improvement in psoriasis-like skin inflammation (Wang 2009).
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