What Is Considered Healthy Eating? An Exploratory Study among College Students of Nutrition and Food Science.

In modern industrialized societies, the focus on healthy eating has increased significantly across multiple sectors, including the media, public policy, expert opinion, and public awareness. The aim of this research was to explore the perceptions of healthy eating and the barriers to adopting a healthy diet among undergraduate students in Human Nutrition and Dietetics (HND) and Food Science and Technology (FST) degrees in Spain. An exploratory and descriptive cross-sectional study was conducted using a qualitative and quantitative methodology and convenience sampling. Two focus groups and a questionnaire were utilized (300 participants from all academic years completed the survey). Differences in definitions of healthy eating and perceived barriers were found between genders and students at different stages of training (p < 0.05). In their understanding of healthy eating, the students placed importance on balance, variety, moderation, and individual factors. Although students considered it easy to follow a healthy diet, family's eating habits, time availability, and emotional states were found to be the main barriers to the implementation of healthy practices. The obtained data supports the need to critically address perceptions of healthy eating throughout the training of nutrition and food science professionals. The insights obtained on the perceived barriers highlight the importance of considering both individual and environmental factors.

Pilot Study on the Prevalence of Diamine Oxidase Gene Variants in Patients with Symptoms of Histamine Intolerance.

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.

Knowledge, attitude, and patient advice on sustainable diets among Spanish health professionals.

Current dietary patterns, especially in high-income countries, are unsustainable. Health professionals, due to their credibility and close contact with the general population, could serve as agents of change for the adoption of sustainable diets. The objective of this study was to assess the knowledge and attitude regarding sustainable diets among the health professionals in Spain. A 24-item online questionnaire was designed for this purpose, and sent to health professionals (i.e., dietitians-nutritionists, nurses, physicians, and pharmacists). From September 2021 to May 2022, 2,545 health professionals answered the survey completely. One-fifth of them had never heard the term "sustainable diet", and most of them recognized having limited knowledge about it. They considered promoting sustainable diets when making dietary recommendations important, and pointed out that they would like to be trained on the topic. Indeed, they reported that all health professionals, independent of their career background, should be educated on sustainable diets. Efforts should be stressed on implementing training courses, at university level but also as continuous post-graduate training, providing health professionals in Spain the necessary knowledge to promote the adoption of sustainable diets among the population.

Comparative Assessment of the Nutritional Profile of Meat Products and Their Plant-Based Analogues.

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.

Perceptions of Food among College Students in the Field of Food Science: A Food Sustainability Approach.

The complex concept of food sustainability has become crucial in all spheres of life. Dietitians, food scientists, and technologists are in a unique position to promote sustainability in food systems. However, the perceptions of food sustainability among food science professionals and college students are under-researched, particularly in Spain. The aim of this study was therefore to analyze perceptions related to food and to food sustainability in a sample of Human Nutrition and Dietetics (HND) and Food Science and Technology (FST) students in Barcelona (Spain). An exploratory and descriptive cross-sectional study was carried out using qualitative and quantitative methodology and convenience sampling. Two focus groups and an online questionnaire were conducted (300 participants completed the survey, 151 from HND and 149 from FST). Although the students expressed concern about food sustainability, their dietary choices were primarily associated with or influenced by taste/pleasure and health/nutrition. The issue of sustainability seemed more internalized by women than men, whereas the generalized conception of a sustainable diet was essentially based on environmental aspects, with socioeconomic dimensions largely overlooked. The concept of sustainability should be promoted among food science students in all its multidimensionality, and actions need to be implemented that bring sustainability closer to students' social practices, which should be incorporated into all university education and that is taught by professors duly trained in the subject.

Knowledge and perceptions of food sustainability in a Spanish university population.

In 2015, the United Nations adopted the 2030 Agenda for Sustainable Development, with 17 Sustainable Development Goals (SDGs) at its core. Besides tackling climate change and the fight to reduce inequality, the SDG number 12 is specifically focused to develop strategies toward food sustainability. The aim of this study, aligned with SDG number 12, was to analyze the level of knowledge and perceptions of food sustainability in a university community from Spain. A descriptive cross-sectional study, based on an online questionnaire, was carried out between July and November 2021 with convenience sampling. The survey included 28 items and was distributed among students, teachers, researchers and administrative staff from a Spanish university. A total of 1,220 participants completed the survey. 70.4% of the respondents heard about the environmental impact of food and more than 50% were aware of the existence of the SDGs. The different aspects related to diet that concerned them the most were food waste, plastic usage, and environmental impact. They reported that a sustainable diet should be mainly based on local and seasonal products and with a low environmental impact as well as no or the minimum food waste. When asked if they were following a sustainable diet, 77% answered affirmatively. Moreover, the food groups more involved in a sustainable diet should be vegetables and fruits, olive oil, legumes, and whole grains. Regarding food waste, 60% of the surveyed population claimed to generate it at home, with the use of leftovers and planning shopping and meals being some of the most important domestic actions to avoid it. Further initiatives must be implemented to increase the level of knowledge as well as to raise the awareness on the importance to translate it into individual and collective actions that allow a shift toward more sustainable practices.

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.

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.

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.

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 < 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.

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.

Differences in Polyamine Content between Human Milk and Infant Formulas.

Human milk is the gold standard for nutrition during the first months of life, but when breastfeeding is not possible, it may be replaced by infant formulas, either partially or totally. Polyamines, which play an important role in intestinal maturation and the development of the immune system, are found both in human milk and infant formulas, the first exogenous source of these compounds for the newborn. The aim of this study was to evaluate the occurrence and evolution of polyamines in human milk during the first semester of lactation and to compare the polyamine content with that of infant formulas. In total, 30 samples of human milk provided by six mothers during the first five months of lactation as well as 15 different types of infant formulas were analyzed using UHPLC-FL. Polyamines were detected in all human milk samples but with great variation among mothers. Spermidine and spermine levels tended to decrease during the lactation period, while putrescine remained practically unchanged. Considerable differences were observed in the polyamine contents and profiles between human milk and infant formulas, with concentrations being up to 30 times lower in the latter. The predominant polyamines in human milk were spermidine and spermine, and putrescine in infant formulas.

Influence of Breastfeeding Factors on Polyamine Content in Human Milk.

The polyamine content of human breast milk, which is the first exogenous source of polyamines for the newborn, can be affected by several factors associated with the mother, the infant, or breastfeeding itself. The aim of this study was to evaluate the influence of different breastfeeding factors on the polyamines found in human milk. For this study, a cohort of 83 mothers was considered for up to 4 months, and a subgroup of 33 mothers were followed during the first six months of breastfeeding. Two breast milk samples were collected at each sampling point (foremilk and hindmilk) and the polyamine content was determined by UHPLC-FL. Polyamine levels varied considerably between the mothers and tended to decrease over time. Putrescine was the minor polyamine, whereas spermidine and spermine contents were very similar. The concentrations of the three polyamines were significantly higher in hindmilk than foremilk (p < 0.001). Spermidine and spermine levels decreased significantly through the lactation progress (p < 0.05). Finally, slightly higher levels of polyamines were observed in the milk of mothers providing partial, rather than full, breastfeeding, although the differences were not significant. The polyamine content in human milk was found to change during a single feed (foremilk versus hindmilk) and as lactation progressed, mainly in response to the specific circumstances of the newborn.

Growth-Promoting Effect of Cava Lees on Lactic Acid Bacteria Strains: A Potential Revalorization Strategy of a Winery By-Product.

The growing trend of circular economy has prompted the design of novel strategies for the revalorization of food industry by-products. Cava lees, a winery by-product consisting of non-viable cells of Saccharomyces cerevisiae rich in ß-glucans and mannan-oligosaccharides, can be used as a microbial growth promoter, with potential food safety and health applications. The aim of this study was to assess in vitro the effect of cava lees on the growth of 21 strains of lactic acid bacteria (LAB) species commonly used as starter cultures and/or probiotics. Firstly, 5% of cava lees was selected as the most effective amount for enhancing microbial counts. After screening different LAB, statistically significantly (p < 0.05) higher microbial counts were found in 12 strains as a consequence of cava lees supplementation. Moreover, a greater and faster reduction in pH was observed in most of these strains. The growth-promoting effects of cava lees on LAB strains supports the potential revalorization of this winery by-product, either to improve the safety of fermented products or as a health-promoting prebiotic that may be selectively fermented by probiotic species.

Occurrence of Polyamines in Foods and the Influence of Cooking Processes.

Dietary polyamines are involved in different aspects of human health and play an important role in the prevention of certain chronic conditions such as cardiovascular diseases and diabetes. Different polyamines can be found in all foods in variable amounts. Moreover, several culinary practices have been reported to modify the content and profile of these bioactive compounds in food although experimental data are still scarce and even contradictory. Therefore, the aim of this study was to evaluate the occurrence of polyamines in a large range of foods and to assess the effect of different cooking processes on the polyamine content of a few of them. The highest level of polyamines was found in wheat germ (440.6 mg/kg). Among foods of a plant origin, high levels of total polyamines over 90 mg/kg were determined in mushrooms, green peppers, peas, citrus fruit, broad beans and tempeh with spermidine being predominant (ranging from 54 to 109 mg/kg). In foods of an animal origin, the highest levels of polyamines, above all putrescine (42-130 mg/kg), were found in raw milk, hard and blue cheeses and in dry-fermented sausages. Regarding the influence of different domestic cooking processes, polyamine levels in food were reduced by up to 64% by boiling and grilling but remained practically unmodified by microwave and sous-vide cooking.

Low-Histamine Diets: Is the Exclusion of Foods Justified by Their Histamine Content?

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.

Inhibition of Biogenic Amines Formation in Fermented Foods by the Addition of Cava Lees.

Food safety can be compromised by some bioactive compounds such as biogenic amines that can be specially found in fermented foods due to the bacterial decarboxylation of some amino acids by fermentative or spoilage bacteria. Cava lees are a winery by-product rich in fiber and phenolic compounds and previous works have raised their revalorization from a food safety point of view. The aim of the current work was to investigate whether the use of cava lees can help to control biogenic amine formation in bread and fermented sausages. In bread, only very low levels of biogenic amines (putrescine, cadaverine, and/or spermidine) were found, whose content did not vary with the addition of different amounts of lees. However, the addition of lees in fermented sausages significantly reduced the formation of tyramine and cadaverine. In sausages spontaneously fermented and inoculated with Salmonella spp., the presence of cadaverine and putrescine diminished by 62 and 78%, respectively, due to the addition of cava lees. The addition of cava lees phenolic extract also showed an anti-aminogenic effect (21% for cadaverine and 40% for putrescine), although in a lesser extent than cava lees. Cava lees and their phenolic extract were shown to be an effective strategy to control the undesirable accumulation of high levels of biogenic amines during the production of fermented products.

Influence of the Type of Breastfeeding and Human Milk Polyamines on Infant Anthropometric Parameters.

Feeding choices in the early months of life are key determinants of growth during infancy. Polyamines participate in cell proliferation and differentiation, and it has also been suggested that polyamine metabolism plays a role in adipogenesis. As the main exogenous source of polyamines in the infant is human milk, the aim of this work was to study if the type of breastfeeding received and the polyamine intake from human milk has an influence on infant anthropometric parameters. A cohort of 78 full-term healthy newborns was followed up until 4 months of age; 55 were fully and 23 partially breastfed. Anthropometric measurements were taken at 2 and 4 months, when human milk samples were also collected for analysis of polyamine content by UHPLC-FL. Fully breastfed infants had a better anthropometric profile than those partially breastfed (p < 0.05). Furthermore, polyamine intake in partially breastfed infants was significantly lower compared to those fully breastfed. However, only two of the 15 anthropometric indicators evaluated (triceps skinfold and mean upper arm circumference) showed a significant inverse association with polyamine content in human milk and intake (p < 0.05). Infant growth and body composition differ according to the type of breastfeeding received. Based on the weak associations between polyamines and anthropometric indicators, it is not possible to conclude the influence of polyamines in infant growth and body composition.

In vitro determination of diamine oxidase activity in food matrices by an enzymatic assay coupled to UHPLC-FL.

Intestinal diamine oxidase (DAO) acts as a protective barrier against exogenous histamine. A deficit of DAO activity can lead to the appearance of histamine intolerance, a clinical condition that may be treated by a low-histamine diet and oral DAO supplementation to enhance intestinal histamine degradation. As sources of DAO, porcine kidneys and certain legume seedlings are suitable components for the formulation of a DAO supplement. The aim of this work was to develop a rapid and reliable methodology for the in vitro determination of DAO activity in food matrices based on an enzymatic assay coupled to UHPLC-FL. The proposed method showed a satisfactory linearity and sensitivity and provided a relative standard deviation lower than 3%, guaranteeing method precision, and a mean recovery greater than 99% both for lyophilized pea sprouts and porcine kidney protein extracts. A high specificity is a key attribute of this method due to the use of histamine as the reaction substrate and the direct quantification of its degradation. Moreover, the lack of interference of catalase and hydrogen peroxide is another advantage in comparison with previously published methods. Lyophilized pea sprouts showed the greatest histamine-degrading activity (0.40 ± 0.01 mU/mg), followed by porcine kidney protein extracts (0.23 ± 0.01 mU/mg) and commercial DAO supplements (0.09 ± 0.06 mU/mg). This technique could be used as a tool to validate the DAO activity of food matrices of potential interest for the treatment of histamine intolerance.

Polyamines in Food.

The polyamines spermine, spermidine, and putrescine are involved in various biological processes, notably in cell proliferation and differentiation, and also have antioxidant properties. Dietary polyamines have important implications in human health, mainly in the intestinal maturation and in the differentiation and development of immune system. The antioxidant and anti-inflammatory effect of polyamine can also play an important role in the prevention of chronic diseases such as cardiovascular diseases. In addition to endogenous synthesis, food is an important source of polyamines. Although there are no recommendations for polyamine daily intake, it is known that in stages of rapid cell growth (i.e., in the neonatal period), polyamine requirements are high. Additionally, de novo synthesis of polyamines tends to decrease with age, which is why their dietary sources acquire a greater importance in an aging population. Polyamine daily intake differs among to the available estimations, probably due to different dietary patterns and methodologies of data collection. Polyamines can be found in all types of foods in a wide range of concentrations. Spermidine and spermine are naturally present in food whereas putrescine could also have a microbial origin. The main polyamine in plant-based products is spermidine, whereas spermine content is generally higher in animal-derived foods. This article reviews the main implications of polyamines for human health, as well as their content in food and breast milk and infant formula. In addition, the estimated levels of polyamines intake in different populations are provided.

Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial.

BACKGROUND & AIMS: Histamine intolerance is a disorder in the homeostasis of histamine due to a reduced intestinal degradation of this amine, mainly caused by a deficiency in the enzyme diamine oxidase (DAO). Among histamine related symptoms, headache is one of the most recorded. Current clinical strategies for the treatment of the symptomatology related to this disorder are based on the exclusion of foods with histamine or other bioactive amines and/or exogenous DAO supplementation. The aim of this study was to assess the efficacy of a food supplement consisting of DAO enzyme as a preventive treatment of migraine in patients with DAO deficiency through a randomized double-blind trial. METHODS: 100 patients with confirmed episodic migraine according to current International Headache Society (IHS) criteria and DAO deficiency (levels below 80 HDU/ml) were randomized in two groups. One group received DAO enzyme supplementation and the other received placebo for one month. Clinical outcomes assessed were duration and number of attacks, perception of pain intensity and adverse effects during treatment. The use of triptans was also recorded. RESULTS: Great variability was found in the duration of migraine attacks reported by placebo and DAO groups. A significant reduction (p = 0.0217) in hours of pain was achieved in patients treated with DAO supplement, with mean durations of 6.14 (±3.06) and 4.76 (±2.68) hours before and after treatment, respectively. A smaller reduction without statistical signification was also observed for this outcome in the placebo group, from 7.53 (±4.24) to 6.68 (±4.42) hours. Only in DAO group, a decrease in the percentage of patients taking triptans was observed. The number of attacks and the scores of pain intensity showed a similar reduction in both groups. No adverse effects were registered in patients treated with DAO enzyme. CONCLUSIONS: Migrainous patients supplemented with DAO enzyme during one month significantly reduced the duration of their migraine attacks by 1.4 h. No statistically significant reduction was found in placebo group before and after treatment. The reduction of pain hours observed in placebo group (0.9 h) could explain the lack of significant differences between both study groups. One month of DAO supplementation has demonstrated a positive trend in the improvement of migraine but more studies with a longer treatment period are needed to better assess the efficacy of DAO supplementation. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN10091019; www.isrctn.org.