Variegate porphyria is the result of decreased protoporphyrinogen oxidase (PPOX) activity, the penultimate enzyme of haem biosynthesis. Haem precursors can produce free radicals and activate oxygen-inducing oxidative stress. Our aim was to analyse the effects of variegate porphyria on haemoglobin levels, antioxidant enzyme activities and oxidative damage in circulating erythrocytes. Twelve women affected by variegate porphyria and 12 control healthy women participated in the study. Women affected by variegate porphyria presented reduced PPOX content and delta-aminolevulinic acid dehydratase activity in erythrocytes. Haemoglobin content and mean corpuscular volume were higher in the porphyric group. Erythrocyte glutathione reductase and superoxide dismutase activities and catalase content were higher in porphyric women, although MDA levels were also higher in the erythrocytes of the porphyric group. In conclusion, the determination of PPOX could be a useful method to detect variegate porphyria. Despite having higher antioxidant defences, erythrocytes of porphyric women have greater oxidative damage and higher corpuscular volume, which are both indices of a situation of higher oxidative stress.

Our aim was to analyse the influence of variegate porphyria (VP) on the antioxidant defenses and markers of oxidative damage and inflammation in plasma and neutrophils and the effects of dietary supplementation with vitamins E and C on these parameters in plasma, neutrophils and erythrocytes. Twelve women affected by VP and twelve pair-matched healthy control women participated in a double-blind crossover study. Each participant took 50 mg/d of vitamin E and 150 mg/d of vitamin C, or a placebo, for 6 months, by consuming an almond-based beverage as the vehicle. Women affected by VP presented higher C-reactive protein and malondialdehyde (MDA) circulating levels. Plasma antioxidant defenses were not different between porphyric and control women. Neutrophils from VP women presented decreased catalase (CAT) and glutathione reductase (GR) activities together with increased protein carbonyl levels. Reactive oxygen species (ROS) production from stimulated neutrophils was also higher in porphyric women than their controls. Dietary supplementation was effective in increasing a-tocopherol levels in neutrophils and in reducing MDA levels in plasma. Erythrocyte CAT and GR activities were enhanced by the enriched beverage only in the control subjects. In conclusion, women affected by VP present a situation of inflammation, plasma oxidative damage and neutrophils more primed to the oxidative burst, with decreased antioxidant activities and increased ROS production capabilities and protein oxidative damage. Dietary supplementation with vitamin E (50 mg/d) and vitamin C (150 mg/d) for 6 months decreased plasma oxidative damage and enhanced the erythrocyte activities of CAT and GR.

SummaryThis study aimed to analyse lymphocyte reactive oxygen species (ROS) production and detoxification mechanisms and the appearance of oxidative damage in variegate porphyria (VP) patients. Twelve women affected by VP and 12 pair-matched healthy control women participated in the study. VP women presented impaired expression of the mitochondrial proteins protoporphyrinogen oxidase, uncoupling protein-3, Bcl-2 and sirtuin 3. Lymphocytes from VP women presented higher H 2 O 2 production than controls after stimulation with phorbol myristate acetate. The inhibition of H 2 O 2 production after in vitro lymphocyte treatment with myxothiazol pointed towards complex III of the mitochondrial respiratory chain as the main contributor of the higher ROS production in porphyric subjects. No differences were observed between VP and control subjects in the levels of DNA damage, assessed by the comet assay method in un-treated lymphocytes. However, DNA damage, expressed both as a percentage of DNA in tail and as the tail moment, was greater in VP women than controls after lymphocyte treatment with H 2 O 2 . In conclusion, lymphocytes from VP women showed impaired expression of mitochondrial antioxidant defences but no significant signs of oxidative stress were evidenced in basal, nonstressing conditions; however, lymphocytes of VP women were more susceptible to producing mitochondrial ROS and to suffering oxidative damage when submitted to stressful situations.

Aims: To describe the nutritional status and dietary practices of patients affected by porphyria variegata, paying special attention to the consumption of nutrients that may help or hinder the condition, and to assess the compliance with prevalent nutritional recommendations. Methods: Cross-sectional study. 24 individuals affected by porphyria variegata (16 females and 8 males; mean age 46.8 (SD 19.5) years) from the Balearic Islands (Spain) recruited through the Balearic Porphyria Association. Dietary questionnaires (7-day dietary record and a semi-quantitative food frequency questionnaire), socio-demographic, lifestyle and health status interviews and anthropometric measurements were carried out. Results: According to current recommendations for the Spanish population and to specific recommendations for porphyria patients, the daily intake of saturated fat (13.2% of total energy), sugars (16.9% of total E), cholesterol (387 mg) and alcoholic beverages (1.1 servings per day) were too high whereas the consumption of total carbohydrates (43.5% of total E), vitamin E (69.5% of RDI), beta-carotene (63.1% of RDI) and vitamin D (42.4% of RDI) was lower than recommended. Conclusions: Dietary pattern observed among porphyria variegata patients was in line with current dietary trends in the Balearic Islands. Nutritional recommendations to these individuals for the management of porphyria are poorly met. It is necessary to translate these recommendations into food-based dietary guidelines based on prevailing dietary patterns.

Lymphocytes from VP patients show reduced PPOX expression and present a greater susceptibility to producing H2 O2 and impaired H2 O2 detoxifying mechanisms. Supplementation with vitamins E and C restores PPOX expression in VP patients and enhances GRd and SOD activity, suggesting the potential benefits of a diet rich in vitamins E and C in these patients.