Psoriasis is a systemic inflammatory disorder that generally comprises excessive production of skin cells leading to patches of thick, scaly, inflamed, often itchy skin. The systemic inflammation underlying psoriasis can also manifest as psoriatic arthritis, a potentially severe arthritic joint condition. About 7.4 million US adults aged 20 or older have psoriasis.

Those with psoriasis have a markedly increased risk of developing other major inflammatory disorders, particularly:

• cardiovascular disease
• diabetes
• metabolic syndrome
• stroke

Note: This link between psoriasis and systemic health is underscored by a 5-year diminished life expectancy among those with the disease, largely attributable to increased cardiovascular disease risk. All people with moderate-to-severe psoriasis should review Life Extension’s protocols on atherosclerosis and cardiovascular disease and chronic inflammation, and be screened for cardiovascular risk factors.

Integrative interventions like fish oil, vitamin D, and pycnogenol have potent anti-inflammatory properties and have been shown to alleviate symptoms of psoriasis.

Causes and Risk Factors

• Genetics is an important contributor in up to 90% of cases, with a variant gene HLA-Cw6 conferring the greatest risk
• There are also many triggers including injury, sunburn, infection, obesity, certain medications, emotional stress, alcohol, and tobacco

Signs and Symptoms

While psoriasis can appear anywhere on the skin, it most often affects the elbows, knees, scalp, lower back, and genitals. Potential signs and symptoms include:

Skin

• Raised, reddish patches covered with thick, silvery-white, shiny scales, which may be itchy
• Pinpoint bleeding spots appear when scales are scraped off (Auspitz sign)

Systemic

• Fever, dehydration, and elevated white blood cell count may occur in severe cases

Other

• Joint stiffness or pain, including inflammation or damage in psoriatic arthritis

Diagnosis

The diagnosis of psoriasis is based on a physical examination of the skin, scalp, and nails. Skin biopsy and blood testing are rarely necessary.

Conventional Treatment

• Topical (eg, corticosteroids and vitamin D analogs): first-line treatment for mild psoriasis
• Systemic medications: affect the whole body; used for more severe forms of psoriasis
• Phototherapy: light therapy for moderate-to-severe psoriasis

Novel and Emerging Strategies

• Fumaric acid esters, which have been shown to lead to complete clinical remission in up to 82.5% of participants, may also ameliorate cardiovascular risk by improving endothelial function.
• Several small molecule drugs and biologics are emerging as therapeutic options for treating psoriasis.

Dietary and Lifestyle Considerations

• A Mediterranean-style diet reduces the severity of psoriasis, with higher consumption of olive oil and fish associated with lower psoriasis severity.
• Climatotherapy and balneotherapy, the medical use of mineral water and mud baths, are shown to be beneficial in psoriasis.
• Good sleep hygiene is helpful, as nighttime melatonin levels are significantly lower in psoriasis patients.

Integrative Interventions

• Fish oil: Fish oil supplements given to psoriasis patients for up to six months resulted in clinical improvement in skin redness, hardening, scaling, and itching.
• Vitamin D: In a 2013 study, psoriasis symptoms significantly improved in patients receiving high daily doses of vitamin D3 in combination with a low-calcium diet.
• Pycnogenol: In a study in psoriasis patients, the addition of pycnogenol to standard treatment resulted in significant improvement in skin redness, hardening, and scaling compared with standard treatment alone.
• White peony extract: A 2014 study showed substantial clinical improvement, along with a significant drop in inflammatory cytokines, in 32% of patients treated exclusively with peony glucosides.
• Whey protein: In one study, administration of whey protein isolate 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.

Psoriasis is a systemic inflammatory disorder that generally comprises excessive production of skin cells leading to patches of thick, scaly, inflamed, often itchy skin. The systemic inflammation underlying psoriasis can also manifest as psoriatic arthritis , a potentially severe arthritic joint condition. About 7.4 million US adults aged 20 or older have psoriasis (Rachakonda 2014; Mayo Clinic 2015; Sen 2014; Parisi 2013; Schalock 2014; Bowcock 2005; Traub 2007; Kurd 2010; Pirro 2015; Elsevier BV 2015).

Psoriasis can be both physically and psychologically debilitating. Those with psoriasis have a markedly increased risk of developing other major inflammatory disorders, particularly atherosclerosis and cardiovascular disease, obesity, diabetes, metabolic syndrome, and stroke (Ni 2014; McDonald 2012; Tobin 2011; Yeung 2013; Benson 2015). The emotional burden of severe psoriasis, historically termed the “heartbreak of psoriasis,” can increase the risk of psychological disorders (Parisi 2013; Schalock 2014; Kurd 2010).

The inflammatory link between psoriasis and systemic health is underscored by reduced lifespan among those afflicted with this disease: moderate-to-severe psoriasis patients have a 5-year diminished life expectancy. This reduced lifespan is largely attributable to increased cardiovascular disease (Ryan 2015; Ni 2014; Reich 2012; Grozdev 2014), so it is crucial that people with psoriasis also review Life Extension’s protocols on atherosclerosis and cardiovascular disease and chronic inflammation.

Conventional psoriasis therapy has considerable limitations including variable treatment response and serious side effects such as potential liver toxicity, as well as increased risk of cancer and infection due to immunosuppressive drugs (Jani 2015; Garcia-Pérez 2013; Grozdev 2014; Lee 2012; Kamangar 2012; Stern 2012; Sivamani 2010).

Fortunately, a number of natural compounds such as omega-3 fatty acids, vitamin D, pycnogenol, and peony extract may confer benefits for psoriasis patients, protect against adverse effects of some psoriasis treatments, and reduce the risk of cardiovascular and other chronic diseases often associated with psoriasis (Millsop 2014; Balbas 2011; Kamangar 2013; Gulati 2015; Wang, Zhang 2014).

A healthful eating pattern—such as the Mediterranean diet—can also help reduce the severity of psoriasis. Weight loss in obese patients can reduce systemic inflammation associated with psoriasis and lead to clinical improvement. Sun exposure and topical moisturizers can help as well (Heier 2011; UMMC 2014a; Barrea 2015; Bhatia 2014; Upala 2015; Millsop 2014).

This protocol will examine the underappreciated link between psoriasis and other serious inflammatory conditions, most notably cardiovascular disease. The causes and triggers of psoriasis, its conventional treatments, and exciting new therapies will be reviewed. Dietary and lifestyle factors along with state-of-the-art natural compounds targeting both the skin manifestations and systemic inflammation of psoriasis will be discussed as well.

Psoriasis results from a complex interaction of the immune cells, skin cells, and inflammatory messengers called cytokines, resulting in an inflammatory cascade that affects not only the skin but tissues throughout the body (Monteleone 2011; Traub 2007; Jariwala 2007; Cai 2012). The skin lesions typical of psoriasis arise when this inflammatory cascade causes skin cells to multiply too quickly. The new skin cells move to the outermost layer of skin in only a few days rather than weeks. Older skin cells cannot be shed fast enough, so they pile up on the surface as thick, silvery, flaky areas of dead skin. Redness and swelling develop as a result of increased blood flow from newly formed capillary blood vessels. This formation of new blood vessels is called angiogenesis and is an important contributor to psoriasis (Liew 2012; AAD 2015; NIH 2013; Das 2009).

Psoriasis Subtypes

There are several subtypes of psoriasis, and an individual can have more than one subtype.

Table 1: Subtypes of Psoriasis

(NIH 2013; Usatine 2013; Schalock 2014; Hall 2015; Armstrong 2014)

Psoriatic Arthritis

Up to 30% of psoriasis patients are diagnosed with an inflammatory joint disease called psoriatic arthritis, though many remain undiagnosed. The pathophysiology of psoriatic arthritis is complex and not completely understood. Scientists suspect that autoimmunity underlies this condition, and an autoantibody correlating with psoriatic arthritis (anti-carbamylated protein) has recently been described (Chimenti 2015). In 10‒15% of psoriatic arthritis cases, joint disease develops before skin symptoms (Villani 2015; Goldman 2016; Hall 2015). Psoriatic arthritis can affect any joint in the body, and can range from mild to severe; frequent flare-ups and remissions are common (Lee 2010; NLM 2015; Girolomoni 2009; Traub 2007). A severe, destructive form of psoriatic arthritis known as arthritis mutilans afflicts a subset of patients. Large prospective studies suggest obesity is a significant risk factor for psoriatic arthritis (Love 2012; Li 2012; Elsevier BV 2015; Goldman 2016).

Psoriatic skin lesions can appear as much as two decades before the onset of arthritis. The severity of skin disease and joint inflammation are not related (Elsevier BV 2015; Hall 2015). Psoriasis of the skin and psoriatic arthritis may be different manifestations of the same underlying inflammatory disease (Hebert 2012; Traub 2007).

The precise cause of psoriasis is unknown. While there is a strong genetic component, psoriasis also has many environmental and lifestyle triggers including injury, sunburn, infection, obesity, certain medications, emotional stress, alcohol, and tobacco (Monteleone 2011; Traub 2007; Jariwala 2007; Cai 2012), which interact with the immune system, causing inflammation and rapid proliferation of skin cells (Siegel 2013; Armstrong 2014; NIH 2013; UMMC 2014a).

Genetics

Psoriasis is a highly heritable disorder, with genetics believed to be an important contributor in up to 90% of cases, and a markedly increased risk in those with a first- or second-degree relative with the condition. The risk of developing psoriasis is 60% in those with two affected parents (Gupta 2014; Eder 2015; Usatine 2013; Hall 2015).

While psoriasis involves multiple genes, a variant gene called HLA-Cw6 appears to confer the greatest risk. This gene is part of a family of genes, referred to as the HLA complex, that is strongly associated with common autoimmune diseases including type 1 diabetes, celiac disease, and multiple sclerosis (Kaukinen 2002; Bahcetepe 2013; Gupta 2014; Delves 2014).

Streptococcal Infection

A streptococcal infection of the throat and tonsils often precedes guttate psoriasis, and streptococcal infections may also exacerbate other types of psoriasis (Armstrong 2014; NIH 2013; Mallbris 2009). The association between streptococcal infection and guttate psoriasis has been known for decades, and is quite strong (Telfer 1992; Leung 1995; Whyte 1964). In one study, psoriasis patients had approximately 10-fold higher frequency of strep throat than healthy controls (Gudjonsson 2003). Also, tonsillectomy has been shown to substantially reduce the severity of psoriasis (Thorleifsdottir 2012).

Table 2: Environmental and Lifestyle Risk Factors for Psoriasis

(Fleming 2015; Adamzik 2013; Armstrong 2014; UMMC 2014a; Schalock 2014; Gudjonsson 2003; Majewski 2002; Majewski 2003; Boyd 1999; Ferri 2015; Usatine 2013; Hirotsu 2012; Li, Qureshi 2013)

Associated Diseases

Systemic inflammation increases risk for several other diseases among psoriasis patients (Ni 2014; Ryan 2015; Siegel 2013; Padhi 2013; Dowlatshahi 2013; McDonald 2012; Tobin 2011):

• cardiovascular disease
• obesity
• diabetes
• high blood pressure
• abnormal blood lipids
• metabolic syndrome
• non-alcoholic fatty liver disease
• cancer
• anxiety and depression
• inflammatory bowel disease
• elevated homocysteine

Symptoms of psoriasis can vary from person to person depending on the type and severity. While psoriasis can appear anywhere on the skin, it most often affects the elbows, knees, scalp, lower back, and genitals. Potential signs and symptoms include (Schett 2011; Liu 2014; Thomson 1990; Usatine 2013; UMMC 2014a; AAD 2015; NIH 2013; Schalock 2014):

• Skin
• Raised, reddish patches covered with thick, silvery-white, shiny scales
• Reddening of skin can also be diffuse and widespread
• Pinpoint bleeding spots appear when scales are scraped off (Auspitz sign)
• Appearance of plaques at site of skin injury or infection (Koebner phenomenon)
• Teardrop-shaped lesions on trunk, limbs, and scalp after viral or bacterial (usually streptococcal) infection
• Pus-filled bumps or blisters on palms and soles
• Skin lesions may be itchy
• Systemic
• Fever, dehydration, and elevated white blood cell count may occur in severe cases
• muscle weakness
• uveitis (inflammation of part of the eye called the uvea)
• Other
• Nail changes – pitting, discoloration, thickening, separation from nail bed
• Joint stiffness or pain, including inflammation or damage in psoriatic arthritis

The diagnosis of psoriasis is based on a physical examination of the skin, scalp, and nails. Skin biopsy and blood testing are rarely necessary (UMMC 2014a; Usatine 2013).

Other skin diseases with a similar appearance are ruled out by differential diagnosis. These include eczema, dermatitis (contact, atopic, seborrheic, nummular), tinea, lichen planus, lichen simplex, pityriasis rosea, cutaneous lupus erythematosus, syphilis, drug reactions, squamous cell carcinoma in situ, and mycosis fungoides (cutaneous T-cell lymphoma) (Armstrong 2014; Usatine 2013; Schalock 2014). If psoriatic arthritis is suspected, rheumatoid arthritis and gout are screened for using laboratory tests and x-rays (Bosmansky 1983; Sankowski 2013; Busse 2010).

An integrated approach to the diagnosis and treatment of psoriasis, with emphasis on comprehensive screening and aggressive treatment of associated conditions (particularly cardiovascular), is important (Ryan 2015; Ni 2014; Padhi 2013; Siegel 2013; Spah 2008). Combining various treatments—topical, phototherapy, systemic drugs—allows lower dosages of each and can improve treatment effectiveness (NIH 2013; UMMC 2014a).

The goals of treatment are to minimize psoriasis symptoms, improve the patient’s quality of life, and achieve and maintain remission with minimal adverse effects (Usatine 2013; Armstrong 2014; AAD 2015).

Typically, treatment options fall into one of three categories (Armstrong 2014; Usatine 2013):

• Topical: first-line treatment for mild-to-moderate psoriasis
• Systemic medications: affect the whole body; used for more severe forms of psoriasis
• Phototherapy: light therapy for moderate-to-severe psoriasis

Topical Therapy

Topical treatments applied directly to plaques include medicated creams, ointments, and lotions. They are usually the first treatment given when psoriasis is diagnosed, and are often combined with stronger therapies (NIH 2013; UMMC 2014a). Topical therapies include:

Table 3: Topical Therapies

(Dawn 2006; Pearce 2006; Usatine 2013; UMMC 2014a; NIH 2013; Schalock 2014; Ferri 2015; Roelofzen 2010; Armstrong 2014; Wang, Lin 2014; Federman 1999; Chiricozzi 2012; Pittelkow 1981; Menter 1983; Stern 1980)

Phototherapy

Phototherapy, or light therapy, is a commonly used and effective psoriasis treatment generally reserved for patients with moderate-to-severe psoriasis (Armstrong 2014). Exposing the skin to ultraviolet light helps control psoriasis by several mechanisms, including destruction of skin-infiltrating T cells, suppression of elevated inflammatory cytokines, and alteration of gene expression (Wong 2013; Furuhashi 2013). Phototherapy can be administered as ultraviolet A (UVA) light in combination with medications, or as variations of ultraviolet B (UVB) light with or without medications (Koo 2000; NIH 2013; UMMC 2014a; Luftl 1998; Schalock 2014).

The benefits of phototherapy can also be obtained naturally through controlled exposure to sunlight, which contains both UVA and UVB (Brenner 2008; Søyland 2011) (see “Dietary and Lifestyle Considerations”).

Ultraviolet B (UVB) phototherapy. There are two types of UVB phototherapies: narrowband and broadband.

• Narrowband UVB is the most commonly used phototherapy for psoriasis as it has the best risk-benefit ratio compared with other types of light therapy (Usatine 2013; NIH 2013).
• Broadband UVB has been used for psoriasis for decades. However, it is not as potent as narrowband UVB or UVA, and is not typically helpful for chronic psoriasis (NIH 2013; Kirke 2007; Usatine 2013).

Psoralens and ultraviolet A (PUVA) phototherapy. PUVA therapy is a combination treatment of a medication called psoralen and UVA radiation. Psoralens (eg, 8-methoxypsoralen, or methoxsalen) are photosensitizing agents that make the skin more sensitive to light. These agents interact with DNA and reduce DNA synthesis upon exposure to UVA, leading to reduced proliferation of skin cells (Stern 2007). PUVA therapy is effective in clearing psoriasis in more than 85% of cases. However, long-term use may increase the risk of squamous cell skin cancer and melanoma (Archier 2012). PUVA usually requires a specialty clinic or hospital, and involves treatment two to three times per week. This treatment can lead to redness, burning and blistering, particularly if dosage is not correctly controlled; it also ages skin, termed “skin photoaging” (Naldi 2009; Tahir 2004; Schalock 2014; Armstrong 2014; NIH 2013; Ferri 2015; HQO 2009).

Systemic Medications

Systemic oral or injectable drugs may be prescribed for more severe forms of psoriasis (Armstrong 2014).

Methotrexate. Methotrexate (Trexall) is a first-line systemic drug used to treat adults with severe psoriasis and psoriatic arthritis whose condition has not responded to topical treatments or phototherapy. The drug slows turnover of skin cells by inhibiting the metabolism of folate, a B vitamin necessary for normal cell metabolism, differentiation, and division (Bailey 1999; Gold Standard 2015; Higdon 2014a). It also has immunosuppressive and anti-inflammatory properties. Methotrexate can cause liver damage and decrease production of red blood cells, white blood cells, and platelets (Kozub 2011; Schalock 2014; Armstrong 2014; NIH 2013).

Retinoids. Retinoids are related chemically to vitamin A. They help regulate growth of skin cells. Retinoid drugs include acitretin (Soriatane) and isotretinoin (Accutane). Retinoids can be effective in severe adult psoriasis that does not respond to other therapies, and are sometimes combined with other treatments. Oral retinoids should not be used by women who are pregnant or may become pregnant since they may cause birth defects (Schalock 2014; Armstrong 2014; NIH 2013).

Cyclosporine. Cyclosporine rapidly suppresses the immune system and slows the growth of skin cells. It powerfully suppresses the immune system and is often used to prevent graft rejection in organ transplant recipients. Cyclosporine is generally reserved for short-term “rescue” use to bring very severe and extensive psoriasis under control; long-term use can cause significant adverse effects including kidney problems, hypertension, and non-melanoma skin cancers (Paul 2003; Armstrong 2014; Schalock 2014; NIH 2013).

Apremilast. Apremilast (Otezla) is an oral anti-inflammatory drug that is approved by the Food and Drug Administration (FDA) for plaque psoriasis and psoriatic arthritis (FDA 2014; Fala 2015). Although the exact mechanism of apremilast’s anti-psoriasis activity remains unclear, this medication inhibits an enzyme called phosphodiesterase 4. By doing so, apremilast appears to interrupt the production of numerous proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), that are elevated in psoriasis. Apremilast was the subject of two randomized controlled trials in which it was superior to placebo for the treatment of psoriasis. Its side effect profile includes depression, suicidal thoughts, fatigue, and insomnia (Zerilli 2015; Paul 2015; Papp 2015).

Biologic response modifiers . Biologic response modifiers, or biologics, are protein-based drugs. They are given by subcutaneous injection or intravenous infusion. Unlike traditional systemic drugs that suppress the entire immune system, biologics target specific parts of the immune system. Biologics are highly effective in treating moderate-to-severe psoriasis, and are FDA approved for treating plaque psoriasis. These drugs can increase risk of serious infection and cancer (NIH 2013; UMMC 2014a; NPF 2015b), but they are less toxic than traditional systemic therapies (Declercq 2013; Mansouri 2015). Examples of biologics used in the treatment of psoriasis include adalimumab (Humira), etanercept (Enbrel), infliximab (Remicade), ustekinumab (Stelara), and secukinumab (Cosentyx) (Armstrong 2014; Schalock 2014; NPF 2015b; Usatine 2013; Sanford 2015; FDA 2015; Bagel 2012).

Systemic Medications

Fumaric acid esters. Fumaric acid is a naturally occurring acid first isolated in 1832 from Fumaria officinalis L., a member of the poppy family. Plants in this family have been used medicinally since ancient times (European Commission 2003). More recently, fumaric acid esters, including dimethylfumarate and salts of monoethylfumarate, have shown promise in treating dermatologic conditions, including psoriasis. In 1994, a combination of dimethylfumarate and three salts of monoethylfumarate, Fumaderm, was approved in Germany for the treatment of psoriasis (Dunn 2013). Fumaric acid esters have been described as safe and effective for the treatment of psoriasis and other dermatologic diseases, and are used off-label to treat psoriasis in many countries (Wollina 2011; Atwan 2015).

Fumaric acid esters can be taken orally and have been shown to be mostly safe, with mild side effects such as flushing and gastrointestinal disturbance (Atwan 2015). A 2014 meta-analysis (pooled analysis of published data) showed fumaric acid treatment was as effective as methotrexate for the treatment of psoriasis (Schmitt 2014). Also, a 2004 trial on 40 psoriasis patients found that fumaric acid esters, particularly dimethylfumarate, led to complete clinical remission in 82.5% of participants at 6 months (Carboni 2004).

In a retrospective study of data from 127 adolescents treated with fumaric acid esters for up to 60 months, researchers found average improvements of up to 66% on standardized psoriasis severity scales. These results were achieved by 36 months, though significant improvements were observed by 6 months (Reich 2016). A trial on 13 psoriasis patients (10 of whom completed the trial) showed that fumaric acid ester treatment for 24 weeks led to significant improvements is psoriasis severity in 80% of participants. Two of three subjects who had insulin resistance at baseline showed normal insulin responsiveness at the end of the study, and highly sensitive C-reactive protein (hs-CRP, a marker of systemic inflammation) improved by a median of 25% among participants who showed clinical psoriasis improvement. The treatment also appeared to ameliorate cardiovascular risk, as endothelial function improved by the end of the treatment period. The researchers suggested future trials investigate the potential of fumaric acid esters to improve cardiovascular outcomes in psoriasis patients (Boehncke 2011).

A 13-week randomized controlled trial on 143 psoriasis patients showed that oral fumaric acid esters plus topical calcipotriol (a vitamin D analog) outperformed fumaric acid esters alone. The combination treatment was more effective and faster acting than standalone fumaric acid esters. Because the combination regimen allowed for a slightly lower dose of fumaric acid esters, the researchers concluded that the risk-benefit ratio favored calcipotriol plus fumaric acid esters over fumaric acid esters alone (Gollnick 2002).

Small molecules. Small molecule drugs such as tofacitinib (Xeljanz) and ruxolitinib (Jakafi) are emerging as therapeutic options for treating psoriasis. Whereas biologics are delivered by subcutaneous or intravenous injection, many small molecule drugs can be administered orally or topically. Also, unlike large, protein-based biologics, these small molecule drugs are less likely to provoke immune reactions (Bagel 2014; Gooderham 2013; Morrow 2004).

• Tofacitinib. Tofacitinib is an immunosuppressant approved for rheumatoid arthritis. This drug blocks enzymes called Janus kinases (JAKs), which is thought to result in suppression of the pro-inflammatory action of several interleukins, including interleukin-6 (IL-6) (Migita 2014; Garcia-Pérez 2013; Levy 2012; Bagel 2014; Patel 2012; Lundquist 2014).

In a 2015 trial, oral tofacitinib was superior to placebo and as safe and effective as etanercept, one of the most widely used injectable biologics, for the treatment of moderate-to-severe plaque psoriasis. Long-term studies are ongoing to confirm efficacy and safety (Bachelez 2015).

• Ruxolitinib. Ruxolitinib is a JAK inhibitor that can be administered topically. In a clinical study, application of ruxolitinib cream for 28 days significantly decreased the extent and severity of psoriasis lesions compared with placebo, with only mild side effects reported. Ruxolitinib is currently under development as a treatment for psoriasis (Gooderham 2013; Garcia-Pérez 2013; Levy 2012; Punwani 2012).

Biologics. Several new biologics are under development for the treatment of psoriasis. These agents target various inflammatory cytokines and their receptors, including IL-17 and IL-12/23 (Garcia-Pérez 2013; Patel 2012).

• Brodalumab. Brodalumab is a human monoclonal antibody that blocks the action of IL-17 by binding to its receptor (Bagel 2014). In one clinical trial, brodalumab demonstrated clearance of nearly two-thirds of psoriasis lesions in patients with severe psoriasis within 12 weeks. Side effects such as upper respiratory infection, low white blood cell count, and suicidality necessitate more extensive trials to confirm safety (Papp 2012; Carroll 2015; Patel 2012).
• Ixekizumab. Ixekizumab is a humanized monoclonal antibody that blocks the actions of IL-17. In a clinical study, the highest injectable dose of ixekizumab (150 mg) completely cleared the skin of approximately 40% of psoriasis patients by 12 weeks, with no serious adverse effects reported. Ixekizumab is currently undergoing further clinical trials (Leonardi 2012; Declercq 2013; Patel 2012; Garcia-Pérez 2013).
• Briakinumab. Briakinumab is a human monoclonal antibody that inhibits the actions of IL-12/23 (Patel 2012; Garcia-Pérez 2013; Gordon 2012). In a large year-long clinical trial, briakinumab was effective in the treatment of moderate-to-severe psoriasis. This study confirmed a previous trial showing that briakinumab can provide considerable relief from psoriasis. Since some adverse effects such as serious infections and skin cancers were reported, additional evaluation of the safety profile of this drug is needed (Gordon 2012; Garcia-Pérez 2013; Patel 2012).

Diet and Exercise

Mediterranean diet. The Mediterranean diet is a healthy eating pattern characterized by generous amounts of fruits and vegetables, whole grains, legumes, fish, seafood, and nuts. Few dairy foods and little meat and meat products are consumed. The diet is rich in extra virgin olive oil, and also includes moderate alcohol intake in the form of wine with meals (Barrea 2015).

A 2015 study found strict adherence to a Mediterranean-style diet reduces severity of psoriasis. Notably, higher consumption of extra virgin olive oil and fish were independently associated with lower psoriasis severity (Barrea 2015; Steffen 2014).

Gluten-free diet. Compared with the general population, patients with psoriasis and psoriatic arthritis have a greater frequency of concurrent autoimmune diseases, including celiac disease. A 2014 review concluded that a gluten-free diet may benefit psoriasis patients who have elevated celiac disease antibodies. In some cases, complete clearance of psoriatic skin was reported following a gluten-free diet (Bhatia 2014; Wu 2012; Addolorato 2003).

Weight loss. A rigorous review and analysis of the medical literature determined that weight loss by means of diet and lifestyle interventions reduces the severity of psoriasis in overweight or obese patients (Upala 2015). Several healthy weight loss strategies are described in the Weight Loss protocol.

Environmental Therapies

Environmental therapy comprises the utilization of environmental factors (eg, sunlight, salt and mineral baths, unique properties of certain geographic regions and climates) to modify the course of a disease. These therapies have been in use for thousands of years, including by the ancient Greeks and Romans. Climatotherapy and balneotherapy are overlapping treatment strategies shown to be beneficial in psoriasis (Riyaz 2011; Kopel 2013; Klein 2011; Roos 2010; Harari 2012).

Climatotherapy. Climatotherapy is based on the healing capacities of environmental factors associated with certain climatic locations, including air, temperature, humidity, barometric pressure, and light. Climatotherapy at the Dead Sea in particular is an effective natural treatment for psoriasis. The low altitude of the Dead Sea—the lowest human-inhabited place on earth at 419 meters below sea level—results in lower-intensity ultraviolet radiation, reducing risks associated with greater exposure duration; also, the unique spectrum of radiation in this region may be particularly beneficial for skin diseases. Bathing in the Dead Sea, which is the saltiest sea in the world and has extremely high mineral concentration, may normalize skin cell proliferation rate (Kazandjieva 2008; Riyaz 2011; Kopel 2013).

Studies of psoriasis patients undergoing Dead Sea climatotherapy have reported impressive results: high response rate, long periods of remission, and partial to complete plaque clearance (Kazandjieva 2008). In one study, Dead Sea climatotherapy improved plaque psoriasis disease severity by 95% in up to three-quarters of subjects. Patients with early-onset psoriasis responded better than late-onset patients (Harari 2012). In another study, Dead Sea therapy resulted in significant improvement in the quality of life of patients with psoriasis and psoriatic arthritis (Kopel 2013).

Balneotherapy. Balneotherapy is the medical use of mineral water and mud baths (Riyaz 2011). In a randomized clinical trial, synchronous balneotherapy—artificial balneotherapy that simulates conditions at the Dead Sea—was superior to UVB phototherapy after 35 treatment sessions and six months of follow-up (Klein 2011). A review of studies found positive clinical results and long remission periods for both natural and artificial balneotherapy (Roos 2010).

Moderate sun exposure (heliotherapy). Two studies, which included a total of 30 patients with moderate-to-severe psoriasis, demonstrated that exposure to sunlight resulted in substantial clinical improvement. All patients stopped taking psoriasis medication four weeks before beginning heliotherapy. The treatment began with 45 minutes of sun exposure on both front and back of the body, with a gradual increase in exposure over the following days. The trials lasted 16 days. No sunburn occurred in these studies. A dramatic reduction of inflammatory cell numbers preceded the skin improvements, suggesting sunlight may act through immune system modulation (Heier 2011; Søyland 2011).

It is important that sun exposure be limited to a duration that does not result in sunburn. While moderate sun exposure may be beneficial in psoriasis, skin damage caused by sunburn may be detrimental (PAPAA 2015).

Moisturizers

The American Academy of Dermatology has called the use of unmedicated topical moisturizers “ an internationally accepted standard adjunctive therapeutic approach to the treatment of psoriasis.” In fact, in controlled trials of corticosteroid topical treatments, in which placebo is essentially an unmedicated moisturizer, placebo response rates of up to 47% have been found, suggesting moisturizers alone have a beneficial effect in psoriasis (Menter 2009).

Various preparations can be used as moisturizers or emollients, including creams, ointments, and oils. Patients should incorporate topical moisturizers into their routines, with application twice daily and after bathing. Using fragrance-free products and washing with moisturizing soaps is also recommended (Schalock 2014; NPF 2015a). Moisturizers promote skin rehydration by reducing water loss through evaporation (Ferri 2015).

Sleep Hygiene

Chronic sleep deprivation impairs the skin’s integrity, weakens its function as a protective barrier, and exacerbates the inflammation of psoriasis (Oyetakin-White 2015; Hirotsu 2012; Kahan 2010; Axelsson 2010).

Melatonin, a hormone produced mainly by the brain’s pineal gland, may play a role in the increased risk of psoriasis associated with sleep disruption. Secreted only during darkness, melatonin regulates the circadian sleep-wake cycle, promotes sleep, and modulates inflammation and immune function (NIH 2015; Li, Qureshi 2013; Esposito 2010; Radogna 2010). Studies have shown that nighttime melatonin levels are significantly lower in psoriasis patients compared with controls (Li, Qureshi 2013; Kartha 2014; Esposito 2010; Mozzanica 1988). Some researchers propose that sleep loss and circadian rhythm disruption should be considered risk factors for the development of psoriasis (Hirotsu 2012; Ando 2015).

A number of strategies for improving sleep quality are described in Life Extension’s Insomnia protocol.

Stress Management

Emotional stress is often a consequence of dealing with psoriasis, but increasing evidence suggests stress also contributes to the development and exacerbation of psoriasis (Ni 2014; Brunoni 2014; Hall 2012; Hunter 2013). Stressful life events have been reported to precede the onset of psoriasis in 44% of patients and trigger flare-ups in 88% of psoriasis patients (Hall 2012). Research suggests the body’s stress response may be impaired in psoriasis (Richards 2005). Therefore managing stress is an important goal for psoriasis patients. More information is available in Life Extension’s Stress Management protocol.

Fish Oil & Omega‑3 Fatty Acids

Reported dosage: 0.5–5.9 grams daily

Because of its anti-inflammatory effects, fish oil has been used as an adjunct to psoriasis treatment. In 2021, the American Academy of Dermatology joined with the National Psoriasis Foundation to issue new guidance on the suggested treatment of psoriasis. Therein, they remarked that “Oral fish oil supplementation may augment the effects of topical, oral-systemic, and phototherapy for chronic plaque psoriasis. It can be considered as an additional supplement in patients with chronic plaque psoriasis” (Elmets 2021).

A 2019 meta-analysis included three trials that reported PASI scores. It found that omega 3 supplementation significantly reduced PASI scores by about 1.6 units. This paper did not report baseline PASI absolute scores for these three trials, precluding firm conclusions about the benefit of the treatment (Clark 2019). A post-hoc analysis of a 2020 randomized controlled trial of herring roe oil in which participants took 2,600 mg of EPA plus DHA showed a significant -2.4 reduction in PASI score in those with a score greater than 5.5 at baseline, after 26 weeks (Tveit 2020).

A 2019 meta‑analysis of 13 randomized controlled trials involving 337 participants evaluated three trials of omega-3 fish oils. These three trials found no significant improvement in PASI scores, and the authors noted that the other trials varied widely in their methods and outcomes assessments (Yang 2019).

Curcumin

Reported dosage: 2–4.5 grams daily (but formulations vary)

Curcumin is a major active constituent of turmeric, a rhizome used for millennia as a traditional culinary ingredient and in Ayurvedic medicine as a remedy for health concerns such as musculoskeletal, digestive, and skin conditions (Aggarwal 2007).

A 16-week, phase III, single-dose, randomized, double-blind, placebo-controlled clinical trial tested orally administered curcumin in 63 patients with mild-to-moderate chronic plaque psoriasis (absolute PASI <10). The treatment group took 2 grams per day of an oral formulation of curcumin called Meriva plus a topical steroid ointment. The other group used only the topical steroid. Median baseline absolute PASI score in the curcumin group was 5.6 versus 4.7 in the placebo group. Both groups experienced a reduction in PASI scores. After 12 weeks, 23 (92%) of patients in the curcumin group and 13 (54%) in the placebo group achieved PASI 50 response, 12 (48%) in the curcumin and three (12%) in the placebo group achieved PASI 75 response, five (20%) in the curcumin and one (4%) in the placebo group achieved PASI 90 response, and three (12%) in the curcumin and one (4%) in the placebo group achieved PASI 100 response. (The mean absolute PASI score at the 16-week mark in the curcumin plus steroid group was 1.4, whereas the steroid-only group’s mean absolute PASI score was 2.5. This study also found that the oral curcumin was well-tolerated (Antiga 2015).

In another double-blind, randomized, placebo-controlled trial, 30 adults with moderate-to-severe psoriasis (absolute PASI ≥ 10) received either acitretin (0.4 mg/kg/day) plus oral nanocurcumin (3 grams/day) or acitretin plus placebo for 12 weeks. The subjects were then followed up for an additional four weeks. Fourteen of 15 patients in the nanocurcumin group and all 15 in the control group completed the study. The primary outcome was improvement in psoriasis severity: median PASI fell from 16.4 to 3.4 in the acitretin plus nanocurcumin group versus a decline from 14.8 to 6.8 in the acitretin-placebo group at week 12; the difference between groups was statistically significant. Moreover, PASI 75 was reached by 43% of subjects taking curcumin plus acitretin compared with 20% in the acitretin plus placebo group. PASI 90 was achieved by 36% of participants taking curcumin and acitretin but just 13% taking acitretin alone. The treatment was generally well tolerated, with some reported side effects that were consistent with known retinoid effects. This small short-term study that tested nanocurcumin only as an adjunct to acitretin. While the results are promising, they do not demonstrate a benefit of curcumin nanoparticles alone (Bilia 2018).

Standard, unformulated curcumin is poorly absorbed when taken by itself. Its absorption and bioavailability have been shown to improve upon formulation with other compounds (eg, lecithin, fenugreek, gamma-cyclodextrin) or compositional changes (eg, micellar formulation) (Tabanelli 2021). Consequently, variations in dosing formulations may account for different results seen in several studies. Nevertheless, as shown by the clinical trials described above, the effect of curcumin supplementation in subjects with psoriasis is directionally consistent with a benefit, though larger, more rigorous trials are warranted.

Probiotics

Reported dosage: Highly variable, but generally between 600,000 CFUs twice daily and 200 billion CFUs daily. Common genera of strains included Lactobacillus, Bifidobacteria, and Streptococcus.

The gut microbiome influences inflammatory processes that affect the entire body (Aziz 2023). Therefore, interventions, like probiotics, that target the gut microbiome have appealed to researchers studying health concerns like psoriasis that involve systemic inflammation. Probiotics are live organisms that, when consumed in adequate amounts, provide some kind of health benefit to the person who consumed them.

A 2024 meta-analysis of five randomized controlled trials, which included 286 participants, found that participants taking probiotics experienced decreased psoriasis symptom severity compared with those taking a placebo. The probiotics given to participants varied considerably, however; some studies used a Lactobacillus rhamnosus formula, some used a combination of Lactobacillus and Bifidobacterium strains, and some included Streptococcus strains. The studies also varied in duration (Wei 2024).

Another comprehensive study combined two approaches: a machine learning analysis of 21,942 adult participants in the United States National Health and Nutrition Examination Survey (NHANES) and a meta-analysis of 11 intervention studies including 723 people with psoriasis. This study found that taking probiotics was not clearly linked with lower odds of psoriasis, but it was linked with better treatment outcomes in people who already had the disease. In four studies with a total of 380 participants, the odds of reaching a PASI 75 response with probiotic treatment were greater than with placebo treatment. The main outcome was psoriasis severity, measured mostly with PASI. Across trials, probiotics significantly improved PASI results, including a mean reduction of about 3.7 points versus controls for change in PASI score, greater odds of reaching PASI 75, and better psoriatic lesion clearance rates (Li 2025).

Quality-of-life results were mixed, though some inflammatory markers such as C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, and IL-6 improved. Important limitations are the small percentage of psoriasis cases in the NHANES dataset as well as its cross-sectional, observational nature. The clinical trials in the meta-analysis portion of the study were fairly dissimilar from one another (which limits the ability to compare them); many were small, and safety and dose-response data were limited. Overall, these findings suggest probiotics appear to help as adjunct therapy for psoriasis (Li 2025).

The probiotic regimens used in studies included in this analysis varied widely. For instance, some studies used single strains such as Bifidobacterium infantis (10 billion colony forming units (CFUs) per day for eight weeks) or Streptococcus salivarius K12 (1 billion CFUs per day for 24 weeks). Other studies used multi-strain products given for eight weeks to six months, so the study does not identify one best formula or dose (Li 2025).

A third meta‑analysis included data from seven studies, comparing a treatment group of 198 patients to a control group of 202 patients. Four of the studies reported the PASI 75 response, which in those studies was reached by 33.6% of participants in probiotic groups and 23.6% of placebo recipients. While not statistically significant, it was directionally suggestive of a benefit and should be confirmed in further rigorous randomized controlled trials. C-reactive protein levels did drop significantly while Dermatology Life Quality Index (DLQI) scores did not reliably drop. The studies varied considerably, however, in blinding, randomization, and the strains that were used (Zhu 2024).

In contrast, a double-blind placebo-controlled 2019 trial found a significant improvement in PASI scores, DLQI scores, and Beck’s Depression Inventory (BDI) scores. The study randomly assigned 50 people into two groups; one group received a probiotic drink with Lactobacillus strains for eight weeks while the second group did not receive any probiotic supplements during the same period. The probiotic group showed statistically significant improvements in all the following parameters compared with the placebo group: BDI, DLQI, PASI, and the psoriasis symptom scale (PSS). Among probiotic recipients, 40% (10 patients) achieved a PASI 50 response and 24% reached PASI 75. In the placebo group, 16% had a PASI 50 response and 8% attained PASI 75 (Moludi 2021).

N-Acetylcysteine

Reported dosage: 600 mg daily

The amino acid N-acetylcysteine (NAC) has antioxidant and anti-inflammatory properties. It is also a building block for L-cysteine, which reduces inflammatory cytokines and serves as a precursor of glutathione. Glutathione scavenges free radicals, particularly oxygen radicals (Pedre 2021; Raghu 2021).

A 2025 open-label, prospective, randomized, controlled clinical trial conducted in Egypt evaluated standard therapy, standard therapy combined with NAC, and standard therapy combined with NAC and vitamin E in 45 people with mild or moderate symptoms of psoriasis vulgaris. Each group had 15 people. The NAC group was given 600 mg of effervescent NAC granules each day for the eight‑week study. The NAC and vitamin E group was given the 600 mg of effervescent NAC granules and a 1,000 mg vitamin E (form not specified) soft gelatin capsule each day of the study. The study found that those given NAC experienced significant improvements: they had a 41% improvement in PASI scores, 49.4% improvement in DLQI scores, and a decrease in inflammatory markers. No significant differences were found between the NAC and the NAC plus vitamin E groups. However, this was a small, open-label, single-center study with only 15 patients per group and mild baseline disease severity (mean PASI scores of 2.87–3.47), limiting the generalizability of findings. The evidence from this study suggests NAC may be a promising adjunctive treatment for mild psoriasis, but larger, blinded, longer-duration trials are needed to establish its clinical utility (Elkalla 2025).

Vitamin D

Reported dosage: between 50 mcg (2,000 IU) per day and 500 mcg (20,000 IU) per week

Vitamin D remains one of the most widely studied supplements in psoriasis, and topical vitamin D analogues are effective in treating psoriasis (Elmets 2021). However, clinical findings related to supplemental oral vitamin D are mixed. A 2025 network meta-analysis found that in 21 randomized controlled trials, those receiving vitamin D supplementation had significantly lower PASI scores (Chen 2025). In the randomized controlled Vitamin D and Omega-3 Trial (VITAL), 25,871 older U.S. adults were assigned to vitamin D3 at 50 mcg (2,000 IU) per day, marine omega-3 fatty acids at 1,000 mg per day, both, or placebo for a median of 5.3 years. Vitamin D supplementation was associated with a modestly lower incidence of confirmed autoimmune disease overall (assessed as a composite of several diseases, including psoriasis). However, psoriasis-specific results were based on very few cases and were not statistically significant. Therefore, this trial supports a possible role for vitamin D in immune regulation, but it does not establish a clear role for vitamin D supplementation in psoriasis prevention (Hahn 2022).

Conversely, a meta-analysis of 23 studies involving 1,876 people with psoriasis and 7,532 people without it (“healthy controls”) found no significant differences in PASI scores after three, six, and 12 months of vitamin D supplementation, even though those with psoriasis had significantly lower serum 25-hydroxyvitamin D concentrations. The dosages and formulations varied: some studies used an induction dose followed by a monthly dose and others used just a biweekly or monthly dose; some studies used vitamin D2 while others used vitamin D3 (Formisano 2023). Also, a 2023 trial that used a 2,500 mcg (100,000 IU) loading dose and a 500 mcg (20,000 IU) per week ongoing dosage for four months found that people in the vitamin D group showed no significant change in PASI scores, Physician Global Assessment (PGA) scores, DLQI scores, or self‑administered PASI scores compared with those in the placebo group (Jenssen 2023). Other trials also showed no significant improvement with vitamin D supplementation (Hata 2014; Theodoridis 2021; Ingram 2018; Jarrett 2018).

On the basis of the inconsistent evidence described in this section, it is reasonable for most psoriasis patients to undergo lab testing to assess their 25-hydroxyvitamin D levels to ensure they have adequate levels (eg, at least > 30 ng/mL) and supplement to boost levels into the adequate range if not.

Nutrients with Preliminary & Inconsistent Evidence

The following nutritional interventions are supported by preliminary or mixed evidence, generally suggesting that they are worth studying further in the context of psoriasis. However, the evidence available as of early 2026 is insufficient to draw firm conclusions about the potential benefits of these nutrients in the context of psoriasis.

Dunaliella bardawil

Dunaliella bardawil is a natural source of 9‑ cis beta‑carotene, which is a precursor of vitamin A. Since the 1930s, vitamin A deficiency has been linked to skin conditions (Greenberger 2012) and standard therapy for psoriasis includes acitretin, a vitamin A metabolite.

In a small, prospective, randomized, double-blinded study, 34 people were given Dunaliella for 12 weeks. The participants took a total of four capsules of Dunaliella for a total of 30–40 mg of 9-cis beta-carotene. At the end of six weeks, those in the Dunaliella group showed reductions in their PASI scores compared with the placebo group, and these results were sustained at 12 weeks. At the 12-week mark, a PASI 75 response was reached in 40.0% of the patients receiving Dunaliella and about 27% of the control patients, though this did not reach the level of significance (Greenberger 2012). The results of this trial were suggestive of a benefit but are ultimately inconclusive. Well-designed studies that demonstrate a significant, conclusive benefit are necessary to determine the utility of Dunaliella in the treatment of psoriasis.

Topical Vitamin B12

A randomized trial in 24 adults with mild-to-moderate plaque psoriasis compared a vitamin B12-containing emollient applied twice daily to affected areas for 12 weeks against a standard emollient for maintenance therapy. The B12 emollient produced greater reductions in lesion severity and extent (Del Duca 2017). An earlier 12-week, randomized, intra-individual comparison in 13 adults tested a B12 cream with avocado oil against the vitamin D3 analog calcipotriol, applied to different psoriatic plaques on the same patient. Calcipotriol worked faster in the first four to eight weeks, but by week 12 the two treatments produced similar reductions in PASI and the B12 cream was better tolerated (Stucker 2001).