Diet and Psoriasis: Part 3. Role of Nutritional Supplements

Fish Oil

Oils of cold water fish rich in omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) have been considered for use in psoriasis treatment. We found a total of fifteen trials evaluating fish oil for the treatment of psoriasis (Table I). Although the populations studied and the outcomes assessed were heterogeneous, overall there was moderate evidence of benefit for the use of fish oil supplements in psoriasis, with 12 trials (6 controlled, 6 uncontrolled) showing clinical benefit in psoriasis and 3 trials (2 controlled, 1 uncontrolled) showing no benefit.

Mayser et al.³ and Grimminger et al.⁴ each conducted double-blind, randomized, controlled studies comparing the effect of intravenous omega-3 fatty acids (Omegaven) to omega-6 fatty acids (Lipoven) for the treatment of psoriasis. In the Mayser et al. study, 75 subjects with chronic plaque psoriasis subjects were randomized to a 14-day treatment with either intravenous omega-3 or omega-6. PASI scores decreased by 11.2 ± 9.8 in the omega-3 group versus 7.5 ± 8.8 in the omega-6 group (p=0.048), with significantly better improvement for the omega-3 group in erythema, scale, and induration. In Grimminger et al., 20 subjects with acute guttate psoriasis received either intravenous omega-3 or omega-6 for 10 days. The omega-3 group demonstrated greater improvement in erythema, scale, and induration compared to the omega-6 group (p<0.05 for all categories). This corresponded to a greater than ten-fold increase in favorable neutrophil leukotriene products seen in the omega-3 group but not in the omega-6 group.

In another double-blind placebo-controlled trial of 24 patients with chronic stable plaque psoriasis, the group that received 10 capsules of MaxEPA (1.8 g EPA, 1.2 g DHA) daily for 12 weeks showed more improvement in itching, erythema, scaling, and affected body surface area than the control group receiving 10 capsules of olive oil a day; however, only the improvement in erythema was statistically significant at 12 weeks⁵. Several uncontrolled, open studies have also shown that supplementation of fish oil, ranging from 0.54 to 13.5 grams EPA and 0 to 9.0 grams DHA daily for 6 weeks to 6 months, resulted in clinical improvement, measured by erythema, induration, and scaling^6-12. These studies have also demonstrated clinical improvement associated with inhibition of leukotriene B4 production in peripheral leukocytes in vitro, decreases in platelet malondialdehyde production, changes in abnormalities of erythrocyte lipid membrane pattern, and increase in leukotriene B5 to leukotriene B4 ratio in peripheral blood neutrophils^{6-9, 13}.

Fish oil appears has also been studied in combination with other therapies. A double-blind, placebo-controlled study of 18 patients with severe stable plaque psoriasis demonstrated a statistically significant improvement of psoriasis on a regimen of fish oil with UVB therapy versus placebo olive oil with UVB¹⁴. An open investigation of 30 patients with mild-to-moderate plaque psoriasis who were given either tacalcitol, a synthetic vitamin D3 analog, or combined tacalcitol and Oravex (2.8 g EPA, 0.4mg DHA), showed highly significant improvement (p<0.0001) in the PASI score in the Oravex group compared to control after 8 weeks¹⁵. Another study of 40 patients with chronic stable plaque psoriasis reported better clinical improvement of psoriasis with fish oil in combination with oral etretinate compared to etretinate monotherapy¹⁶.

There have also been several trials that have not shown significant improvement in psoriasis with fish oil (Table I). These studies utilized 1.8 to 3.2 g daily EPA and 1.2 to 2.2 g daily DHA^{11, 17, 18}. In one randomized, double-blinded, controlled trial of 27 patients with psoriasis, there was no significant clinical difference between experimental fish oil group, which received 1.8 g EPA and 1.2 g DHA daily for eight weeks, and the control olive oil group¹⁷. Another randomized, double-blinded, controlled study of 145 patients with moderate to severe psoriasis showed no significant difference in PASI or patient reported subjective score between the group receiving fish oil and the placebo group receiving corn oil¹⁸. A third open study that included 21 patients with plaque psoriasis also showed no clinically significant improvement following fish oil supplementation for six to eight weeks, although a single patient with pustular psoriasis showed significant improvement¹¹.

The most common side effects of fish oil include nausea, which may be dose dependent, indigestion, diarrhea, and fishy taste in the mouth.

Vitamin D

Vitamin D deficiency associated with psoriasis has been reported^19-21. We identified seven prospective trials of vitamin D3 supplementation in psoriasis and two trials in psoriatic arthritis (Table II). All were open-label uncontrolled studies except for one randomized, placebo-controlled trial. The forms of vitamin D3 used in these trials varied from 1,25-dihydroxyvitamin D3 (calcitriol, the physiologically active form of vitamin D) to 1-alpha-hydroxyvitamin D3 (alfacalcidol, requiring only liver metabolism to be converted to the active form) to vitamin D3 (cholecalciferol, requiring both liver and kidney metabolism to become active).

Perez et al. performed a single center open trial to assess the safety and efficacy of oral 1,25-dihydroxyvitamin D3 for the treatment of psoriasis. Patients (n=85) were given 0.5 μg daily oral calcitriol, which was increased by 0.5 μg every 2 weeks as long as lab values were normal, for a period of six months to 36 months. Overall, 88% had some level of clinical improvement of psoriasis during the study period.²² 26.5% had complete improvement, 36.2% had moderate improvement, 25.3% had slight improvement of psoriasis, and 12% had no improvement. Additionally, the mean PASI scores decreased from 18.4 at baseline to 9.7 at 6 months to 7.8 at 24 months of treatment (p<0.001).

Five additional open-label uncontrolled studies investigated the role of oral vitamin D supplementation in a smaller numbers of psoriasis patients ranging from seven to seventeen. In three of those trials, moderate or greater improvement in psoriasis was reported in at least 50% of subjects^23-25. For the other two trials, one showed statistically significant improvement in mean PASI from baseline but results for individual subjects were not given²⁶, while in the other trial only 25% of patients showed moderate or better improvement²⁷. Additionally, two small trials have shown benefit of oral vitamin D on psoriatic arthritis as measured by the Disease Activity Score (DAS28)²⁸ or tender joint count²⁹.

In the only randomized, placebo-controlled trial of vitamin D supplementation reported to date, 9/20 (45%) receiving 1 μg daily of 1-hydroxyvitamin D3 showed slight improvement versus 8/21 (38%) in the placebo group, which was not statistically significant³⁰.

Possible side effects of oral vitamin D supplementation include hypercalcemia, hypercalciuria, and kidney stones. Long-term vitamin D overdose can also lead to bone demineralization. Some studies reported an increase in blood levels of calcium and vitamin D or an increase of calcium in urine after starting oral supplementation^29-31, but no patient experienced adverse clinical side effects^29-34.

Vitamin B12

Vitamin B12 deficiency associated with psoriasis has been reported^{31, 32}. A retrospective observational study of 98 patients with plaque psoriasis and 98 healthy controls demonstrated lower vitamin B12 levels in psoriasis patients compared to healthy controls³¹. However, few studies have investigated the role of intramuscular administration of vitamin B12 in the treatment of psoriasis. Ruedemann found favorable results with the administration of 1,000 g per cubic centimeter of vitamin B12 intramuscularly for 10 consecutive days, followed by a maintenance dose³³. Thirty-two percent (11/34) of patients cleared their psoriasis lesions and 29% (10/34) reached PASI 75. Six of 34 patients initially reported severe pruritus, which resolved after two to three treatments. However, no baseline levels were taken prior to administering vitamin B12 to these subjects.

In contrast to these positive results, a double-blinded controlled study by Baker and Comaish showed no difference with the use of intramuscular vitamin B12 injections for psoriasis³⁴. In this study involving 73 patients, intramuscular injections of 1,000 ug vitamin B12 or placebo were administered five days weekly for three weeks. No statistically significant benefit in vitamin B12 group was observed compared to placebo.

Vitamin B12 has no common side effects reported. Rare side effects include hypersensitivity reaction, nausea, vomiting, myalgia and swelling.

Selenium

Selenium is an essential element with anti-proliferative and immunoregulatory properties. A prospective study by Serwin et al. found that a decline in serum selenium was related to increased psoriasis disease severity in patients with psoriasis for more than three years (p<0.05)³⁵. Several trials have assessed the role of selenium supplementation in psoriasis. Kharaeva et al. enrolled 58 subjects in a double-blind placebo-controlled clinical study to compare the effects of combined selenium aspartate, coenzyme Q10, and Vitamin E versus placebo for the treatment of severe erythrodermic and arthropathic forms of psoriasis³⁶. They found that supplementation with the combination of antioxidants showed statistically significant clinical improvement of psoriasis by PASI and Severity Score (SS), the latter which included symptom scoring for desquamation of plaques, plaque hyperemia, plaque inflammation, nail dystrophy, and joint pain (p<0.05). The study also showed decline in oxidative stress, measured through activity level of enzymes such as catalase and superoxide dismutase, with the antioxidant supplementation.

In contrast, a double-blind, parallel group study of 37 patients by Serwin, Wasowicz, and Chodynicka demonstrated that selenium supplementation plus narrowband UVB was not superior to placebo plus narrowband UVB for psoriasis treatment³⁷. In another case-control study by Serwin et al., 22 patients received topical 5% salicylic acid ointment, 0.1% to 0.3% dithranol ointment, and 200 μg daily selenomethionine versus placebo for 4 weeks³⁸. Both groups achieved almost complete remission, but the PASI score was higher in the selenium group (p < 0.05) and the TNF level was also higher in the selenium group. Another small prospective study involving 7 patients showed that 6 weeks of 400 μg daily selenium increased the number of dermal CD4+ cells, but did not result in any clinical improvement in the patients³⁹.

Side effects with selenium are quite uncommon and are observed at doses above 400 mcg/day. They include nausea, vomiting, nail changes, loss of energy, and irritability. Long-term selenium toxicity can mimic arsenic poisoning and can include nail changes, nausea, vomiting, garlic breath, metallic taste, and hair loss.