Danno K., Sugie N. Combination therapy with low-dose etretinate and eicosapentaenoic acid for psoriasis vulgaris. Sigmundsdottir H., Pan J., Debes G.F., Alt C., Habtezion A., Soler D., Butcher E.C. Effect of omega-3 fatty acids on disease severity in patients with psoriasis: A systematic review. In conclusion, evidence from large-scale trials about the clinical significance of carotenoids remains contradicting. Similarly, another case-control study, which included 37 patients, showed that selenium supplementation as add-on treatment to narrowband UVB therapy did not significantly improve psoriasis severity (assessed by PASI score) and TNF-R1 and CRP concentrations compared to placebo [234]. More specifically, the study included 18 patients who were advised to initially consume 170 g of white fish daily for 4 weeks and then they were randomized to consume either 170 g of white fish or 170 g of oily fish daily for six weeks; at the end of this second period, the diets were reversed for a further 6 weeks. 8600 Rockville Pike Naldi L., Conti A., Cazzaniga S., Patrizi A., Pazzaglia M., Lanzoni A., Veneziano L., Pellacani G. Psoriasis Emilia Romagna Study Group. Dietary lipids include cholesterol and fatty acids (FAs), with the latter playing a crucial role in inflammation and immunity. The impact of 1,25(OH)2D3 on keratinocytes by inhibiting proliferation of hyperproliferative cells and increasing differentiation, together with its actions on T-cell activation, has rendered it a possible treatment option for patients with psoriasis [190,191]. Omentin-1 is another adiponectin with anti-inflammatory properties by inhibiting TNF-. Retinoic acid promotes phagocytosis and activation of natural killer (NK) T-cells and, therefore, vitamin A deficiency has been associated with defective immune responses [101,102]. Kratz M., Kuzma J.N., Hagman D.K., van Yserloo B., Matthys C.C., Callahan H.S., Weigle D.S. Such results by single studies have been confirmed in a large meta-analysis including 54 studies and 19.372 patients, which showed that obesity is associated with 60% higher odds of inadequate response to anti-TNF treatment as compared to normal BMI; for each unit increment of BMI, there is an augmentation in odds of failure by 6.5% [137]. Antioxidant Rich Potato Improves Arterial Stiffness in Healthy Adults. Nicklas B.J., Ambrosius W., Messier S.P., Miller G.D., Penninx B.W., Loeser R.F., Palla S., Bleecker E., Pahor M. Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: A randomized controlled clinical trial. Furthermore, curcumin may enhance the secretion of anti-inflammatory cytokines such as IL-10 [240].

Bahraini et al. Impact of body mass index and obesity on clinical response to systemic treatment for psoriasis.

Antiga E., Bonciolini V., Volpi W., Del Bianco E., Caproni M. Oral Curcumin (Meriva) Is Effective as an Adjuvant Treatment and Is Able to Reduce IL-22 Serum Levels in Patients with Psoriasis Vulgaris. Carnevale R., Pastori D., Nocella C., Cammisotto V., Bartimoccia S., Novo M., Del Ben M., Farcomeni A., Angelico F., Violi F. Gut-derived lipopolysaccharides increase post-prandial oxidative stress via Nox2 activation in patients with impaired fasting glucose tolerance: Effect of extra-virgin olive oil. Another prospective study showed that a weight loss >5% is significantly associated with the achievement of minimal disease activity as a response to anti-TNF treatment in obese patients with psoriatic arthritis [158]. Levels of omentin-1 are decreased in obesity, however, an inverse association with the incidence of psoriasis has not been firmly established [141]. Naldi L., Addis A., Chimenti S., Giannetti A., Picardo M., Tomino C., Maccarone M., Chatenoud L., Bertuccio P., Caggese E., et al. Kyriakou A., Patsatsi A., Sotiriadis D., Goulis D.G. Miller I.M., Ellervik C., Yazdanyar S., Jemec G.B.

In an RCT by Grimminger et al., 20 patients were hospitalized for acute guttate psoriasis (BSA > 10%) and randomly received either an n-3 lipid emulsion (2.1 g EPA, 2.1 g DHA) or a conventional n-6 lipid emulsion for 10 days. The same group examined the effect of selenium supplementation on TNF-R1 levels as add-on strategy to topical treatment with salicylic acid and dithranol ointment. Jeong E.A., Jeon B.T., Shin H.J., Kim N., Lee D.H., Kim H.J., Kang S.S., Cho G.J., Choi W.S., Roh G.S. Fahy E., Subramaniam S., Murphy R.C., Nishijima M., Raetz C.R., Shimizu T., Spener F., van Meer G., Wakelam M.J., Dennis E.A. reported that low selenium concentration is associated with increased severity of psoriasis in patients with disease duration more than three years [230]. Juhlin et al. Similarly, another recent study investigated the effect of low-calorie ketogenic diet in 30 patients with psoriasis by evaluating clinical symptoms, biochemical markers, metabolomic profile and inflammatory markers (IL-2, IL-4, IL-1, TNF-, IFN-). In a sub-study associated with the Prevencin con Dieta Mediterrnea (PREDIMED) trial, individuals receiving Mediterranean diet plus EVOO showed a reduction in IL-6, VCAM-1, ICAM-1 and LDL, and an increase in HDL [82]. Effects of extra virgin olive oil and fish oil on lipid profile and oxidative stress in patients with metabolic syndrome. Mobarhan S., Bowen P., Andersen B., Evans M., Stacewicz-Sapuntzakis M., Sugerman S., Simms P., Lucchesi D., Friedman H. Effects of beta-carotene repletion on beta-carotene absorption, lipid peroxidation, and neutrophil superoxide formation in young men. Murray M.L., Bergstresser P.R., Adams-Huet B., Cohen J.B. showed that obesity is associated with a two-fold increased risk of psoriasis compared to individuals with normal body weight. A narrative literature review on epigallocatechin gallate and its biophysical properties for topical use in dermatology. Responses of inflammatory markers to a low-fat, high-carbohydrate diet: Effects of energy intake. Chiricozzi A., Raimondo A., Lembo S., Fausti F., Dini V., Costanzo A., Monfrecola G., Balato N., Ayala F., Romanelli M., et al. Omega-3 FAs include -linolenic acid (ALA) which is mainly found in plants, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found mainly in fish and seafood sources. In addition, bariatric surgery, particularly gastric bypass, reduces the risk of developing psoriasis (HR: 0.52) [155]. Frasheri L., Schielein M.C., Tizek L., Mikschl P., Biedermann T., Zink A. Lipidomic evidence that lowering the typical dietary palmitate to oleate ratio in humans decreases the leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes. Evidence from the Psocare project. Even more interestingly, vitamin D and analogues have the same efficacy as topical corticosteroids without the adverse effect of skin atrophy, and they are thus suitable for long-term treatment. A prospective study by Merola et al., including 70,743 female nurses who completed semi-quantitative food frequency questionnaires in 1994, 1998, 2004 and 2006, showed no association between vitamin D intake and the development of psoriasis [199]. Del Giglio et al. However, data about more sophisticated nutritional patterns, such as ketogenic, very low-carb or specific macro- and micro-nutrient substitution, are scarce. Conversely, Burrows et al. Vitamins C and E are associated with a reduction in coronary artery disease, but their supplementation in high pharmacological doses seems to bear no additional benefit [107]. Hask G., Pacher P. Endothelial Nrf2 activation: A new target for resveratrol? Prevalence of Obesity in Patients with Psoriasis: Results of the National Study PsoHealth3. Engelman C.D., Meyers K.J., Iyengar S.K., Liu Z., Karki C.K., Igo R.P., Jr., Truitt B., Robinson J., Sarto G.E., Wallace R., et al. Silveira B., Oliveira T., Andrade P.A., Hermsdorff H., Rosa C., Franceschini S. Dietary Pattern and Macronutrients Profile on the Variation of Inflammatory Biomarkers: Scientific Update. Postprandial serum endotoxin in healthy humans is modulated by dietary fat in a randomized, controlled, cross-over study. McKenzie R.C. Siddiqui et al. Before Sabat R., Philipp S., Hoflich C., Kreutzer S., Wallace E., Asadullah K., Volk H.D., Sterry W., Wolk K. Immunopathogenesis of psoriasis. Darghosian L., Free M., Li J., Gebretsadik T., Bian A., Shintani A., McBride B.F., Solus J., Milne G., Crossley G.H., et al.

In accordance with these results, another RCT with 23 patients who received supplementation with 100.000 IU Vitamin D/month and 42 controls showed that there was no significant difference in any of psoriasis outcome measures (PASI, PGA, PDI) after 12 months [202]. Research data regarding the effect of n-3 polyunsaturated fatty acids on the treatment of psoriasis are inconsistent. Yu G., Rux A.H., Ma P., Bdeir K., Sachais B.S. Vitamin A is present both in plants (carrots and red peppers) as carotenoids and in eggs, liver and milk as retinol, with both forms being processed to its active form, which is retinoic acid. Stratigou T., Dalamaga M., Antonakos G., Marinou I., Vogiatzakis E., Christodoulatos G.S., Karampela I., Papavassiliou A.G. Hyperirisinemia is independently associated with subclinical hypothyroidism: Correlations with cardiometabolic biomarkers and risk factors. Bilia A.R., Bergonzi M.C., Isacchi B., Antiga E., Caproni M. Curcumin nanoparticles potentiate therapeutic effectiveness of acitrein in moderate-to-severe psoriasis patients and control serum cholesterol levels. In a subgroup analysis, higher dosages of >1800 mg/day and <8 weeks in duration were associated with more beneficial outcomes [222]. Apart from weight loss per se, such results can be explained also by the effect of physical activity, which upregulates anti-inflammatory molecules such as IL-10 and downregulates TLR expression on monocytes, leading to more favorable immune responses. Skyvalidas D.., Mavropoulos A., Tsiogkas S., Dardiotis E., Liaskos C., Mamuris Z., Roussaki-Schulze A., Sakkas L.I., Zafiriou E., Bogdanos D.P. Fairris G.M., Lloyd B., Hinks L., Perkins P.J., Clayton B.E. Interestingly, increased leptin levels have also been detected in patients with psoriasis independently of BMI. Markova M., Pivovarova O., Hornemann S., Sucher S., Frahnow T., Wegner K., Machann J., Petzke K.J., Hierholzer J., Lichtinghagen R., et al. Since fruits are also rich in other components, such as vitamins and fiber, some studies in animal models have used purified polyphenol extracts to address their role more specifically. Moreover, subjects with a body weight increase >10 kg had an RR of 1.72 [129]. ); moc.liamtoh@09KaniretaK (A.K. sharing sensitive information, make sure youre on a federal Experimental data both in vivo and in vitro, human epidemiological studies and randomized controlled trials have established the role of dietary components in chronic inflammation and oxidative stress. Sun and ski holidays improve vitamin D status, but are associated with high levels of DNA damage. In addition, in some studies where no correlation between vitamin D and PASI was found, analysis was limited to only one measurement per person and not on repeated measurements over a follow-up period, while the relationship between PASI and 25(OH)D has not been shown to be linear, either. Stranges S., Marshall J.R., Natarajan R., Donahue R.P., Trevisan M., Combs G.F., Cappuccio F.P., Ceriello A., Reid M.E. As mentioned above, apart from being a calcium-regulating vitamin, vitamin D also exerts anti-inflammatory effects. The effect of dietary fish oil supplementation on psoriasis. According to an observational cohort study based on Danish and Icelandic registries, BMI > 30 is associated with higher psoriasis activity at baseline and reduced drug response and treatment adherence (HR:1.85) [135]. The first one consists of saturated fatty acids (SFAs), such as palmitic acid and lauric acid, while the second one comprises monounsaturated (MUFAs), such as n-9 oleic acid (OA), and polyunsaturated (PUFAs) fatty acids, such as a-linolenic acid (ALA) and linoleic acid (LA), depending on the number of double bonds they contain. Rapid improvement of clinical manifestations and changes in neutrophil leukotriene profile. Holmer-Jensen J., Karhu T., Mortensen L.S., Pedersen S.B., Herzig K.H., Hermansen K. Differential effects of dietary protein sources on postprandial low-grade inflammation after a single high fat meal in obese non-diabetic subjects. Instead, a diet rich in vegetables and fruits such as the Mediterranean diet seems to be the safest and most established pattern to prevent metabolic and immune derangement. Curcumin inhibits LPS-induced inflammation in rat vascular smooth muscle cells in vitro via ROS-relative TLR4-MAPK/NF-kappaB pathways. Another trial indicated that oral curcumin administration in combination with visible light phototherapy can improve moderate to severe plaque psoriasis [243], and a similar result was demonstrated with curcumin as an add-on therapy to acitretin [244]. Jacobi A., Langenbruch A., Purwins S., Augustin M., Radtke M.A. Jensen P., Zachariae C., Christensen R., Geiker N.R., Schaadt B.K., Stender S., Hansen P.R., Astrup A., Skov L. Effect of weight loss on the severity of psoriasis: A randomized clinical study. Gorjao R., Hirabara S.M., de Lima T.M., Cury-Boaventura M.F., Curi R. Regulation of interleukin-2 signaling by fatty acids in human lymphocytes. Neuhouser M.L., Schwarz Y., Wang C., Breymeyer K., Coronado G., Wang C.Y., Noar K., Song X., Lampe J.W.

This results in a metabolism switch to fat consumption as a main source of energy. Similarly, in a 12-week study, subjects who received n-3 supplementation showed a 14% decrease in lipopolysaccharide (LPS) stimulated interleukin 6 (IL-6) production, while a decrease in the n-6:n-3 ratio led to reductions in stimulated IL-6 and TNF- production [32]. This research received no external funding. FOIA The beneficial effect of olive oil and, especially, extra virgin olive oil (EVOO) has been demonstrated in a number of studies [72,73,74,75,76,77]. Lassus A., Dahlgren A.L., Halpern M.J., Santalahti J., Happonen H.P. Dewell A., Marvasti F.F., Harris W.S., Tsao P., Gardner C.D. Orgaz-Molina J., Buendia-Eisman A., Arrabal-Polo M.A., Ruiz J.C., Arias-Santiago S. Deficiency of serum concentration of 25-hydroxyvitamin D in psoriatic patients: A case-control study. Nyirenda M.H., Sanvito L., Darlington P.J., OBrien K., Zhang G.X., Constantinescu C.S., Bar-Or A., Gran B. TLR2 stimulation drives human naive and effector regulatory T cells into a Th17-like phenotype with reduced suppressive function. Johnston A., Arnadottir S., Gudjonsson J.E., Aphale A., Sigmarsdottir A.A., Gunnarsson S.I., Steinsson J.T., Elder J.T., Valdimarsson H. Obesity in psoriasis: Leptin and resistin as mediators of cutaneous inflammation. Effects of weight loss and long-term weight maintenance with diets varying in protein and glycemic index on cardiovascular risk factors: The diet, obesity, and genes (DiOGenes) study: A randomized, controlled trial. The effects of protein intake on metabolic derangement and inflammation are rather conflictive, and large-scale studies on the association between long-term habitual protein intake and circulating inflammatory biomarkers are lacking. HHS Vulnerability Disclosure, Help Esposito K., Giugliano D. Mediterranean diet for primary prevention of cardiovascular disease. [238]. Mediterranean Diet Foundation Expert Group Mediterranean diet pyramid today. Stroher D.J., Escobar Piccoli Jda C., Gullich A.A., Pilar B.C., Coelho R.P., Bruno J.B., Faoro D., Manfredini V. 14 Days of supplementation with blueberry extract shows anti-atherogenic properties and improves oxidative parameters in hypercholesterolemic rats model. Another study including 40 patients with psoriasis showed that oral etretinate treatment in combination with fish oil had better clinical outcomes on psoriatic manifestations compared to etretinate monotherapy. Low- and high-dose plant and marine (n-3) fatty acids do not affect plasma inflammatory markers in adults with metabolic syndrome. Apart from low-calorie diets, a number of nutrition strategies and dietary patterns such as gluten-free diet, Mediterranean diet and very-low-carb ketogenic diet have been proposed for weight loss achievement in patients with psoriasis. Katsarou A.I., Kaliora A.C., Chiou A., Kalogeropoulos N., Papalois A., Agrogiannis G., Andrikopoulos N.K. Petersen B., Wulf H.C., Triguero-Mas M., Philipsen P.A., Thieden E., Olsen P., Heydenreich J., Dadvand P., Basagaa X., Liljendahl T.S., et al. In recent decades, numerous studies have focused on the association between the inflammatory process and the development of chronic, non-communicable diseases (NCD), such as obesity, diabetes mellitus, cardiovascular diseases, cancer and autoinflammatory diseases such as rheumatoid arthritis and psoriasis [1]. Mandl J., Szarka A., Banhegyi G. Vitamin C: Update on physiology and pharmacology. Apart from genetic and environmental factors, nutrition has emerged as a potential modulator of immunological and inflammatory responses [2]. government site. Li Y., Yao J., Han C., Yang J., Chaudhry M.T., Wang S., Liu H., Yin Y. Quercetin, Inflammation and Immunity. Moreover, obesity exerts a negative impact on the treatment of psoriasis and increases the adverse effect of anti-psoriatic drugs [134,135,136,137,138]. Christen W.G., Cook N.R., Van Denburgh M., Zaharris E., Albert C.M., Manson J.E. A growing body of evidence indicates that dietary nutrients can activate the immune system and may lead to the overproduction of pro-inflammatory cytokines. A similar anti-inflammatory effect was shown in a study where 105 individuals were assigned to one of the three energy-restricted diet groups receiving rice bran, rice husk powder and control (low-calorie only) diet for 12 weeks, with the intervention groups demonstrating decreases in hsCRP and IL-6 compared to controls [51]. Furthermore, psoriasis severity (assessed by PASI score and CRP) was negatively associated with the intake of extra virgin oil, fruits, nuts, fish or seafood, vegetables and legumes, whereas it was positively correlated with red meat intake [175].

Apart from their actions on innate immunity, n-3 PUFAs are crucial in the function of adaptive immunity as well, acting on T cells by regulating the janus kinasessignal transducer and activator of transcription proteins (JAK-STAT) pathway by decreasing JAK1 and JAK3 phosphorylation and, thus, leading to inhibition of STAT5 phosphorylation [42]. Di Nardo V., Gianfaldoni S., Tchernev G., Wollina U., Barygina V., Lotti J., Daaboul F., Lott T. Use of curcumin in psoriasis. Another food source rich in phenolic compounds is olive oil, which is a basic component of Mediterranean diet. conducted a randomized, controlled, double-blinded trial including 50 patients who received 1 g/day Vitamin D3 supplementation or placebo. evaluated the efficacy of a weight loss program with ketogenic diet as a first-line strategy in drug-naive patients with psoriasis. A modified Mediterranean diet score is associated with a lower risk of incident metabolic syndrome over 25 years among young adults: The CARDIA (Coronary Artery Risk Development in Young Adults) study. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. Curcumin, a flavonoid that is mainly found in turmeric, curry spice, and ginger, has been shown to decrease SOD, malondialdehyde (MDA) and CRP in patients with metabolic syndrome and IL-1, TNF-, ICAM-1 and VCAM-1 in mice, through the inhibition of the TLR4 signaling pathway [69,70]. The phenolic compounds in EVOO are capable of diminishing LDL oxidization and possess potent antioxidant properties, with oleuropein also having anti-proliferative properties [7]. Christodoulatos G.S., Spyrou N., Kadillari J., Psallida S., Dalamaga M. The role of adipokines in breast cancer: Current evidence and perspectives. Hernez ., Sanllorente A., Castaer O., Martnez-Gonzlez M.., Ros E., Pint X., Estruch R., Salas-Salvad J., Corella D., Alonso-Gmez .M., et al. Indeed, the optimal level of sun exposure to maintain an adequate vitamin D status is yet to be determined, while a number of other factors such as alcohol intake, physical activity and genetic polymorphisms play an important role; in fact, dietary intake seems to be of little significance [113,114].

and transmitted securely. In the study by Clemmensen et al. Similarly, according to a casecontrol study, patients with psoriasis have lower 25-hydroxyvitamin D (25(OH)D) levels compared to the control group and are more likely to have 25(OH)D deficiency [194]. A study from De Bastiani et al. Bittiner S.B., Tucker W.F., Cartwright I., Bleehen S.S. A double-blind, randomised, placebo-controlled trial of fish oil in psoriasis. Furthermore, it was pointed out that psoriasis may be associated with gluten sensitivity without celiac disease, as elevated values of CD antibodies may exist even with negative duodenal biopsy results [162]. The same factors were examined in a recent meta-analysis, including 7 prospective studies and 17.637 patients; for each 5 units increase in BMI and for each 5 kg of weight gain, the relative risk of psoriasis increased by 19% and 11%, respectively. Many studies have pointed out the beneficial effect of a diet rich in polyphenol sources on inflammation and human health [57]. In this cascade, inflammation plays a cardinal role by promoting hyper-proliferation and angiogenesis, leading to the typical skin lesions and the articular involvement of psoriatic arthritis [8]. Effect of virgin olive oil and thyme phenolic compounds on blood lipid profile: Implications of human gut microbiota. In a study by Zhang et al. In accordance with these results, a more recent cross-sectional observational study with a larger sample (n = 35.735 patients) by Phan et al. was the first that showed that patients with psoriasis had a lower adherence to MD (assessed by PREMIDED questionary) compared to control group. Manning J., Mitchell B., Appadurai D.A., Shakya A., Pierce L.J., Wang H., Nganga V., Swanson P.C., May J.M., Tantin D., et al. In a mouse model of imiquimod-induced psoriasis, resveratrol administration significantly diminished the severity of skin lesions and was associated with beneficial modifications in expression of retinoic acid stimulated genes, and IL-17A and IL-19 mRNA levels [247]. Vitamin D intake and season modify the effects of the GC and CYP2R1 genes on 25-hydroxyvitamin D concentrations. Obesity can also modify pharmacokinetics of anti-TNF and other biologic agents, leading to increased drug clearance, shorter half-life and lower serum trough drug concentrations [132]. about a 40-year-old female patient with recurrent moderate-to-severe plaque psoriasis, psoriatic arthritis and metabolic syndrome who was initially treated with biological therapy (adalimumab) for six months. Finicelli M., Squillaro T., Di Cristo F., Di Salle A., Melone M.A.B., Galderisi U., Peluso G. Metabolic syndrome, mediterranean diet, and polyphenols: Evidence and perspectives. During recent years, it has been shown that weight loss through diet and physical exercise reduces oxidative stressors, exerts a positive effect on psoriasis severity and ameliorates the response to pharmacological treatment for psoriasis. investigated the impact of a nutritional supplement rich in n-3 fatty acids (560 mg EPA, 80 mg DHA, Ovarex) in thirty patients with psoriasis, who received either 2 capsules of Ovarex daily as add-on treatment to topical tacalcitol or only topical treatment with tacalcitol (control group). The ketone metabolite -hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Finally, n-3 PUFAs lead to a reduced production of TNF-, IL-2, IL-4 and IL-10, often in a dose-dependent manner [43]. In conclusion, according to The Medical Board of the National Psoriasis Foundation, vitamin D supplementation is not recommended in patients with psoriasis and normal serum Vitamin D levels. Lyte J.M., Gabler N.K., Hollis J.H. These results implied that only inorganic Se compounds with cytostatic and cytotoxic activity may be of benefit to psoriasis patients; in addition, it was suggested that TNF-R1 reflects residual inflammation after clinical improvement of psoriatic lesions and that such high residual levels may be also attributed to the immunomodulating properties of selenium supplementation. Endothelial expression of E-selectin is induced by the platelet-specific chemokine platelet factor 4 through LRP in an NF-kappaB-dependent manner.