Effect of diet and weight loss on the severity of psoriasis

The consequence of obesity is NAFLD → an increase in MTX hepatotoxicity and the risk of liver fibrosis during therapy (monitoring this risk using elastography) [37, 38].

In contrast, MTX reduces the risk of cardiovascular disease (low doses with folic acid! to prevent the formation of atherogenic homocysteine) [39].

Cs-A is lipophilic and binds to lipoproteins → atherogenic dyslipidemia in obesity → disruption of pharmacokinetics [39, 40].

High BMI limits drug distribution → an increase in toxicity (which is why the dose is calculated due to the patient's appropriate body weight) [41].

However, the increase in creatinine levels was higher in the group of the patients who received the weight-adjusted dose than in the group on the new, weight-independent regimen [42].

Obesity as a risk factor for hypertension increases the probability of its development and nephrotoxicity during therapy [39, 40].

A weight loss of 5–10% improves the effects of Cs-A treatment in the obese; a low calories diet can be a complement to therapy [43].

Hypercholesterolemia with ↓ HDL and hypertriglyceridemia are a common side effects in patients treated with acitretin, especially associated with diabetes, obesity or alcohol addiction [15, 39].

Disorders of lipid and glucose metabolism during treatment were transient and were not associated with changes in BMI, concentration of adipokines associated with obesity (TNF-α, resistin, adiponectin) [44].

Obesity does not affect the effectiveness of PUVA, because the dose of psoralen is calculated according to body weight.

However, patients may be more exposed to developing erythema or burns due to their closer distance to the light source [37].

Increased body weight requires a change in the dosage of biological drugs (ustekinumab, infliximab). Excessive body weight increases the volume of distribution, which results in a decrease in drug concentration [45].

In obesity, TNFα production is increased. The role of iTNF is to eliminate its excess from the circulation and psoriatic lesions, which is why these drugs may be less effective in obese patients:

• - the percentage of patients with PASI 75 decreases with increasing BMI, regardless of gender, severity of lesions and prior treatment [21].

• - only a 160mg loading dose followed by 80 mg of adalimumab causes effective disease remission in obese psoriasis patients [46].

• - lower body weight is a predictor of long-term results of iTNF treatment efficacy [47].

During iTNF therapy, an increase in body weight was observed, on average 2–3 kg after 6 months of treatment [38, 48], however iTNF may improve insulin sensitivity causing hypoglycemia particularly in patients receiving insulin [49].

In contrast to infliximab, ustekinumab does not cause ↑ BMI in treated patients [50].

Secukinumab - no BMI changes during treatment and no difference in PASI reduction depending on BMI [51], but the effectiveness is lower in patients with BMI> 30.

Ixekizumab is more effective in overweight patients, regardless of BMI, even with primary or secondary resistance to secukinumab [52, 53].

Tildrakizumab - safety and efficacy of treatment does not depend on coexisting metabolic syndrome and obesity [54].

Risankizumab - there is no significant difference in PASI reduction depending on BMI, even >30, although blood levels in patients >100 kg are 30% lower than in patients with lower body weight, but they still are within the therapeutic range [55].

Guselkumab is not reported to increase body weight and showed sustained superior efficacy, regardless of bodyweight [56].

Apremilast → PDE4 inhibition → slight weight loss during therapy [57], about 20% of patients reduce body weight by 0.5% due to [58]:

• - Increase in energy expenditure,

• - Improvement of glucose metabolism,

• - Increase in metformin activity,

• - Lipolysis and regulation of white adipose tissue [37, 49].

Tofacitinib - after treatment, an increase in HDL-C, but also LDL-C, total cholesterol, ApoB and ApoA-I (decrease in cholesterol catabolism), improvement of markers of HDL antiatherosclerosis function [59, 60].

Fumaric acid esters (FAE) - the positive effect on cardiovascular and metabolic diseases through their anti-inflammatory and antioxidant properties (endothelial protection, reduction of insulin resistance, decrease of C-reactive protein, and increase of adiponectin) [61, 62].

Reduction of visceral fat, a source of pro-inflammatory cytokines and adipokines,

Decrease in supply of arachidonic acid, a source of pro-inflammatory LTB4

↓CD4+ lymphocyte activity and increase in anti-inflammatory IL-4 concentration,

↓free radicals (the role of oxidative stress)

Reduction of keratinocyte proliferation [100]

↓supply of sulfur (red meat) → ↓hydrogen sulfide → undamaged gut mucosa is impermeable to bacteria, that can’t activate the Toll-like and NF-kB inflammatory pathway receptors [101]

Improvement of skin lesions (PASI reduction) and faster achievement of minimal PsA activity [102, 103]

Improving the metabolic profile (↓ of cholesterol, LDL, serum triglycerides) [104]

Rapid ↓ visceral fat volume → ↓ production of pro-inflammatory mediators

Reduction of pruritus, improvement of skin lesions (PASI reduction) and DLQI [105]

Anti-inflammatory action (MUFAs, oleic acid, polyphenoles, antioxidant agents, and the inhibitor of cyclooxygenase-2, resveratrol)

Dietary fiber favoring beneficial effects on gut microbiota and improve the gut immune responses

Patients adhering to diet achieved PASI reduction faster compared to non-adherents [106, 107]

Improving the metabolic profile (lipid profile) [108]

↓ supply of arachidonic acid → ↓ B4 leukotriene production and ↑ anti-inflammatory IL-4

↓ restoration of normal neutrophil activity (↓ lactoferrin, a marker of their activity).

During fasting, joint pain in PsA decreases

Reduction of skin lesions in psoriasis and pustular psoriasis of the feet [109]

Psoriasis susceptibility loci overlap with CD

The role of gut-skin axis (activation of Th1 and Th17)

CDs are more common in psoriasis, and psoriasis is more common in CDs, and the CD patients were at 1.7 times higher risk of developing new onset psoriasis [81]

BUT: There is no effect of increased gluten intake on psoriasis [83]

Dietary weight reduction in patients with BMI>25

ω-3 PUFAs (oily fish: sardines, salmon, mackerel, herring, tuna and vegetable oils: linseed, rapeseed, soybean, corn oil) - wild fish (not farmed),

Antioxidants such as selenium (oat, brown rice, pumpkin seeds, poultry, fish), coenzyme Q, vitamin E per day and polyphenols in natural pigments (dark grapes, blueberries, black elderberries, cranberries),

Only in case of gluten intolerance, glute-free diet is recommended (elimination of wheat, rye, barley and oats).

Red meat, animal fats and offal

Restriction of dairy products (SFA)

Nightshade vegetables (tomatoes, paprika, chili-pepper, eggplant, pepper)

All types of alcohol should be avoided (except for a glass of red wine containing resveratrol)

Highly processed foods containing preservatives and fried foods (damage of essential non-saturated fatty acids in high temperature and formation of harmful and carcinogenic compounds: acrolein and acrylamide)

Excessive consumption of products containing caffeine and spicy food is not recommended