Sonia Sanchez Perez

Scopus Publications

Improvement of Histamine Intolerance Symptoms in Pregnant Women with Diamine Oxidase Deficiency: An Exploratory Study
Adriana Duelo, Sònia Sánchez-Pérez, Salvador Pellicer-Roca, Sara Sánchez-Buxens, Oriol Comas-Basté, M. Luz Latorre-Moratalla, M. Carmen Vidal-Carou
Journal of Clinical Medicine, 2025
Background/Objectives: Diamine oxidase (DAO) deficiency can lead to excessive histamine absorption at the intestinal level, triggering symptoms that affect the gastrointestinal, neurological, dermatological, respiratory, circulatory, and musculoskeletal systems. This condition, known as histamine intolerance, is more prevalent in women. While serum DAO levels have been observed to increase during pregnancy in healthy women, there is a lack of in-depth studies evaluating the relationship between pregnancy, DAO activity, and histamine intolerance symptoms. This is the first study to assess serum DAO activity before, during, and after pregnancy, as well as the evolution of histamine intolerance symptoms in women diagnosed with this condition. Due to low histamine, diets are quite restrictive, no dietary intervention was considered for pregnant women. Methods: This prospective observational study used an assessment questionnaire to evaluate the presence or absence of histamine-related symptoms in 30 adult women with histamine intolerance before, during, and after pregnancy. Serum DAO activity was also measured at the three time points. Results: Nearly all women (27 out of 30) experienced symptom improvement during pregnancy (p < 0.001). Specifically, at least 77% of women reported a marked reduction in flatulence, bloating, headache, rhinorrhea, flushing, pruritus, hypotonia, or muscle pain. Concurrently, the DAO activity significantly increased 11-fold from the baseline, coinciding with symptom relief. At two months postpartum, symptoms tended to reappear, accompanied by a significant decrease in DAO activity in all participants. Conclusions: This first-of-its-kind observational study demonstrates an improvement in histamine intolerance symptoms and an increase in serum DAO activity during pregnancy. The pronounced symptom relief suggests that restrictive diets, such as low-histamine diets, may not be necessary during pregnancy. Further research is required to confirm these novel findings.
Study Protocol for a Prospective, Unicentric, Double-Blind, Randomized, and Placebo-Controlled Trial on the Efficacy of a Low-Histamine Diet and DAO Enzyme Supplementation in Patients with Histamine Intolerance
Adriana Duelo, Sònia Sánchez-Pérez, Ana Ruiz-Leon, Francesc Casanovas-Garriga, Salvador Pellicer-Roca, Irache Iduriaga-Platero, Judit Costa-Catala, M. Veciana-Nogués, Joaquim Fernández-Solà, Rosa Muñoz-Cano, Joan Bartra, Andrea Combalia, Oriol Comas-Basté, Rosa Casas, M. Latorre-Moratalla, Ramon Estruch, M. Vidal-Carou
Nutrients, 2025
Background/Objectives: Histamine intolerance is primarily caused by a deficiency in the diamine oxidase (DAO) enzyme at the intestinal level. The reduced histamine degradation in the gut leads to its accumulation in plasma, thereby causing multiple clinical manifestations, such as urticaria, diarrhea, headache, dyspnea, or tachycardia, among others. The dietary management of this food intolerance consists of the follow-up of a low-histamine diet, often combined with DAO supplementation. To date, around twenty studies have investigated the effectiveness of these dietary strategies in reducing the frequency and/or intensity of symptoms, with promising results. However, the limitations of these studies (small patient cohort, lack of control group, and short dietary intervention periods) highlight the need for more ambitiously designed research. Therefore, the main objective of this prospective, unicentric, double-blind, randomized, and placebo-controlled trial is to evaluate the efficacy of a low-histamine diet and/or DAO supplementation over a three-month period in improving symptoms of histamine intolerance. Additionally, the impacts of these dietary strategies on the intestinal microbiota composition, urinary profile of histamine metabolites, serum DAO activity, and plasma histamine levels will be assessed throughout the intervention. Methods: The trial will enroll 400 patients who will be randomly assigned to one of two groups: the intervention group, which will follow a low-histamine diet, or the control group, which will maintain their habitual dietary habits. Within each of these groups, participants will be further divided into four subgroups to receive either exogenous DAO enzyme supplementation (from porcine or plant sources, with the latter administered at two different dosages) or a placebo. Therefore, a total of eight distinct intervention groups will be considered. The comparison of these groups will allow the evaluation of the individual effects of the low-histamine diet or DAO enzyme supplementation, as well as their possible synergistic effect. Results: The results of this study should help to improve dietary recommendations for histamine-intolerant patients and ultimately enhance their quality of life.
Impact of technological factors on diamine oxidase (DAO) activity in porcine kidney extracts as active ingredient for the dietary management of histamine intolerance
Judit Costa-Catala, Salvador Pellicer-Roca, Irache Iduriaga-Platero, Sònia Sánchez-Pérez, M. Teresa Veciana-Nogués, M. Luz Latorre-Moratalla, M. Carmen Vidal-Carou, Oriol Comas-Basté
Applied Food Research, 2024
Histamine intolerance is associated with impaired histamine metabolism due to diamine-oxidase (DAO) enzyme deficiency at intestinal level. The recommended strategy to alleviate the symptomatology is a low-histamine diet supplemented with DAO. Different sources of DAO enzyme have been characterized in the literature (animal, vegetal and microbial), although only the porcine kidney protein extract has been approved as food supplement. Despite optimistic clinical results of DAO supplementation, variability in enzymatic activity of this type of active ingredient is reported, potentially linked to manufacturing processes. The aim of this work was to evaluate the impact of the raw material and the technological process of obtaining the porcine kidney protein extract on DAO activity, and its evolution during storage at room temperature (25°C) and refrigeration (4°C). Twenty batches of DAO-containing extract were analyzed and found to have a consistent histamine-degrading activity. The powder extract was prepared by mincing and homogenizing porcine kidneys, defatting with acetone, and drying at 40°C for 6 hours. The inclusion of a biocidal step before acetone extraction was evaluated on DAO activity. The use of sodium hypochlorite and irradiation (8kGy) did not have a negative impact on DAO activity. Moreover, the inclusion of an initial freeze-drying step of the raw material yielded an extract with higher DAO activity. On the other hand, the effect of applying higher temperatures (70°C, 80°C, and 90°C) during the extract drying process for 3 and 6 hours was evaluated, reporting a significant decrease of the enzymatic activity, with losses of 10-20% for every 10°C increase in temperature. Refrigeration was the only storage method capable of preserving enzymatic activity for at least 24 months. The manufacturing and storage of porcine kidney extract are crucial steps in the formulation of DAO supplements suitable for the treatment of histamine intolerance.
Pilot Study on the Prevalence of Diamine Oxidase Gene Variants in Patients with Symptoms of Histamine Intolerance
Adriana Duelo, Oriol Comas-Basté, Sònia Sánchez-Pérez, M. Teresa Veciana-Nogués, Eva Ruiz-Casares, M. Carmen Vidal-Carou, M. Luz Latorre-Moratalla
Nutrients, 2024
A retrospective pilot study was carried out to investigate the prevalence of four variants of the diamine oxidase (DAO) encoding gene (AOC1) in Caucasian adults with symptoms of histamine intolerance. In a cohort of 100 patients and 100 healthy individuals, DAO-encoding gene non-synonymous Single Nucleotide Variations (SNVs) were genotyped by multiplex single-nucleotide primer extension (SNPE) and capillary electrophoresis, and serum DAO activity was analyzed with a radio-extraction assay. The study found that 79% of individuals with symptoms of histamine intolerance harbored one or more of the four SNVs associated with reduced DAO activity. No significant differences were found in the prevalence of any variant between the group of patients and healthy controls. However, when considering the status of the alleles associated with DAO deficiency, more homozygous alleles were observed in histamine-intolerant patients. Moreover, a slightly but statistically higher percentage of patients had a high genetic risk score, reflecting the cumulative effect of carrying multiple DAO deficiency-associated gene variants and a high load of risk alleles (homozygous). A relationship between serum DAO activity and the genetic load of one specific SNV was observed, with DAO activity being significantly lower in patients homozygous for rs2052129. These results potentially support that carrying multiple DAO deficiency-associated gene variants and a high load of risk alleles (homozygous) is more relevant than the mere presence of one or more SNVs. Further studies are needed to determine the predictive value of these DAO-encoding gene variants.
Comparative Assessment of the Nutritional Profile of Meat Products and Their Plant-Based Analogues
Judit Costa-Catala, Natalia Toro-Funes, Oriol Comas-Basté, Salvador Hernández-Macias, Sònia Sánchez-Pérez, M. Luz Latorre-Moratalla, M. Teresa Veciana-Nogués, Victòria Castell-Garralda, M. Carmen Vidal-Carou
Nutrients, 2023
Vegetarian and vegan diets are increasingly being adopted in Spain, a trend mainly driven by ethical concerns for animal welfare and the environment. This has resulted in a growing market for plant-based substitutes of meat products. However, available data on the nutritional value of such meat analogues in Mediterranean countries are still limited. In this study, the labelling information of four categories of plant-based meat analogues (n = 100) and the corresponding conventional meat products (n = 48) available on the Spanish market was surveyed and compared. The nutrient content of plant-based meat analogues varied significantly, due to the wide range of ingredients used in their formulation. Some of these products were found to have a low protein content, which in others was enhanced by the addition of cereals and legumes. Compared to the meat products, the plant-based analogues contained lower levels of total fat as well as saturated fat, which ranged from 30% of total fat in burgers to less than 15% in meatballs, sausages, and nuggets; in contrast, they contained higher amounts of fiber and complex carbohydrates. Overall, the meat analogues cannot be considered as nutritionally equivalent substitutes to conventional meat products due to a high variability of protein content and other nutrients.
The dietary treatment of histamine intolerance reduces the abundance of some histamine-secreting bacteria of the gut microbiota in histamine intolerant women. A pilot study
Sònia Sánchez-Pérez, Oriol Comas-Basté, Adriana Duelo, M. Teresa Veciana-Nogués, Mercedes Berlanga, M. Carmen Vidal-Carou, M. Luz Latorre-Moratalla
Frontiers in Nutrition, 2022
Restrictive diets for the treatment of different gastrointestinal disorders are reported to change the composition of intestinal microbiota. Recently, it has been proposed that individuals with histamine intolerance suffer from intestinal dysbiosis, having an overabundance of histamine-secreting bacteria, but how it is still unknown this state is affected by the usual dietary treatment of histamine intolerance [i.e., low-histamine diet and the supplementation with diamine oxidase (DAO) enzyme]. Thus, a preliminary study was carried out aiming to evaluate the potential changes on the composition of the intestinal microbiota in a group of five women diagnosed with histamine intolerance undergoing 9 months of the dietary treatment of histamine intolerance. After sequencing bacterial 16S rRNA genes (V3-V4 region) and analyzing the data using the EzBioCloud Database, we observed a reduction in certain histamine-secreting bacteria, including the genera Proteus and Raoultella and the specie Proteus mirabilis. Moreover, it was also observed an increase in Roseburia spp., a bacterial group frequently related to gut health. These changes could help to explain the clinical improvement experienced by histamine intolerant women underwent a dietary treatment.
1-methylhistamine as a potential biomarker of food histamine intolerance. A pilot study
Sònia Sánchez-Pérez, Ricard Celorio-Sardà, M. Teresa Veciana-Nogués, M. Luz Latorre-Moratalla, Oriol Comas-Basté, M. Carmen Vidal-Carou
Frontiers in Nutrition, 2022
Efforts are currently being directed to identify a non-invasive marker that can serve as a solid and clinically irrefutable diagnostic criterion for histamine intolerance associated with diamine oxidase (DAO) deficiency. Accordingly, the identification of biomarkers of histamine (HA) metabolism in urine is proposed as a possible new diagnostic strategy. It is hypothesized that individuals with histamine intolerance could have a different urinary profile of HA and its metabolites in comparison with the healthy population. Thus, the aim of this study was to assess the urinary excretion of HA and 1-methylhistamine (MHA) in individuals diagnosed with histamine intolerance and in a control group. Levels of HA and MHA were compared between 24 h and first morning spot urine in a subgroup of 14 control individuals. Then, HA and MHA concentrations in spot urine of 32 histamine intolerant and 55 control individuals were determined by ultra-high performance liquid chromatography and fluorometric detection (UHPLC-FL) and normalized by creatinine. No differences were found between HA and MHA levels in 24 h and first morning samples. Overall, histamine intolerant patients presented a distinct urinary excretion profile compared to the control group due to lower levels of MHA. No differences in urinary MHA were observed related to serum DAO activity. Spot urine samples were thus validated as a reliable tool to determine the urinary excretion of HA and MHA. These results constitute a starting point for the study of HA metabolomics as a suitable and non-invasive approach to histamine intolerance diagnosis.
The Rate of Histamine Degradation by Diamine Oxidase Is Compromised by Other Biogenic Amines
Sònia Sánchez-Pérez, Oriol Comas-Basté, Judit Costa-Catala, Irache Iduriaga-Platero, M. Teresa Veciana-Nogués, M. Carmen Vidal-Carou, M. Luz Latorre-Moratalla
Frontiers in Nutrition, 2022
Nowadays, certain uncertainties related to the onset of histamine adverse effects remain unsolved and still require further research. Questions still to be resolved include the wide range of doses at which dietary histamine may trigger symptoms of intoxication (100–10,000 mg/kg) or the appearance of symptoms of histamine intolerance after the consumption of foods presumable without histamine. It seems feasible that other amines, by acting as competitive substrates, could interfere with histamine degradation by the intestinal enzyme diamine oxidase (DAO). Therefore, the aim of this study was to elucidate the interference of different amines on the rate of histamine degradation by DAO. A series of in vitro enzymatic assays were performed using histamine as the reaction substrate combined with different proportions of putrescine, cadaverine, tyramine, spermidine, and spermine (1:0.25, 1:1, 1:4, 1:20). Putrescine and cadaverine significantly delayed histamine degradation at all tested concentrations (p &lt; 0.001). The greatest effect was observed when putrescine or cadaverine concentrations were 20-fold higher than that of histamine, its degradation being reduced by 70 and 80%, respectively, compared to histamine alone (28.16 ± 1.0 mU). In contrast, tyramine, spermidine and spermine significantly inhibited the histamine degradation rate only at the highest concentration (1:20), reducing it by 32–45%. These results demonstrate that other biogenic amines interfere with histamine metabolization by DAO in vitro, the extent depending on the substrate. These findings could explain why susceptibility to dietary histamine is so variable and account for the discrepancies in the scientific databases regarding the amount of histamine that triggers adverse health effects.
Intestinal Dysbiosis in Patients with Histamine Intolerance
Sònia Sánchez-Pérez, Oriol Comas-Basté, Adriana Duelo, M. Teresa Veciana-Nogués, Mercedes Berlanga, M. Luz Latorre-Moratalla, M. Carmen Vidal-Carou
Nutrients, 2022
An underlying cause of histamine intolerance is diamine oxidase (DAO) deficiency, which leads to defective homeostasis and a higher systemic absorption of histamine. Impaired DAO activity may have a genetic, pharmacological or pathological origin. A recent proposal also suggests it can arise from an alteration in the gut microbiota, although only one study has explored this hypothesis to date. A greater abundance of histamine-secreting bacteria in the gut could lead to the development of histamine intolerance. Thus, the aim of this study was to characterize the composition of the intestinal microbiota of patients with histamine intolerance symptoms and compare it with that of healthy individuals. The study was performed by sequencing bacterial 16S rRNA genes (V3-V4 region) and analyzing the data using the EzBioCloud Database. Dysbiosis of the gut microbiota was observed in the histamine intolerance group who, in comparison with the healthy individuals, had a significantly lower proportion of Prevotellaceae, Ruminococcus, Faecalibacterium and Faecablibacterium prausnitzii, which are bacteria related to gut health. They also had a significantly higher abundance of histamine-secreting bacteria, including the genera Staphylococcus and Proteus, several unidentified genera belonging to the family Enterobacteriaceae and the species Clostridium perfringens and Enterococcus faecalis. A greater abundance of histaminogenic bacteria would favor the accumulation of high levels of histamine in the gut, its subsequent absorption in plasma and the appearance of adverse effects, even in individuals without DAO deficiency.
Low-histamine diets: Is the exclusion of foods justified by their histamine content?
Sònia Sánchez-Pérez, Oriol Comas-Basté, M. Teresa Veciana-Nogués, M. Luz Latorre-Moratalla, M. Carmen Vidal-Carou
Nutrients, 2021
A low-histamine diet is currently the most advised strategy to prevent the symptomatology of histamine intolerance. Conceptually, these diets should be founded on the exclusion of histamine-containing foods, although a certain disparity is found within the list of excluded foods in accordance with the different low-histamine diets available in the literature. This study aimed to critically review low-histamine diets reported in the scientific literature, according to the histamine and other biogenic amine contents of the excluded foods. A total of ten scientific studies that provided specific recommendations on the foods that must be avoided within the framework of a low-histamine diet were found. Overall, the comparative review brought out the great heterogenicity in the type of foods that are advised against for histamine intolerant individuals. Excluded foods were, in most cases, different depending on the considered diet. Only fermented foods were unanimously excluded. The exclusion of 32% of foods could be explained by the occurrence of high contents of histamine. The presence of putrescine, which may interfere with histamine degradation by the DAO enzyme at the intestinal level, could partly explain the reason why certain foods (i.e., citrus fruits and bananas) were also frequently reported in low-histamine diets. Finally, there was a range of excluded foods with an absence or very low levels of biogenic amines. In this case, certain foods have been tagged as histamine-liberators, although the mechanism responsible has not yet been elucidated.
Histamine intolerance: The current state of the art
Oriol Comas-Basté, Sònia Sánchez-Pérez, Maria Teresa Veciana-Nogués, Mariluz Latorre-Moratalla, María del Carmen Vidal-Carou
Biomolecules, 2020
In vitro determination of diamine oxidase activity in food matrices by an enzymatic assay coupled to UHPLC-FL
Oriol Comas-Basté, M. Luz Latorre-Moratalla, Sònia Sánchez-Pérez, M. Teresa Veciana-Nogués, M. Carmen Vidal-Carou
Analytical and Bioanalytical Chemistry, 2019
Biogenic amines in plant-origin foods: Are they frequently underestimated in low-histamine diets?
Sònia Sánchez-Pérez, Oriol Comas-Basté, Judit Rabell-González, M. Veciana-Nogués, M. Latorre-Moratalla, M. Vidal-Carou
Foods, 2018