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September 18, 2019 EventiUncategorized

Sabato 12 ottobre 2019, presso lo Hyatt Centric di Milano Centrale si terrà il seminario di

“Immunomodulazione. Patologie Autoimmuni ed Infezioni Virali Croniche”

Saranno trattati argomenti di interesse immunologico.
Dalle reattività di tipo autoimmune alle allergie e ai tumori, saranno spiegati i meccanismi immunologici alla base delle principali reazioni degli anticorpi e citochine.
Saranno illustrate le principali tecniche di analisi di laboratorio salivari per valutare le principali citochine.

Docente: Dott. Giuseppe Di Fede (Responsabile Scientifico)

Il Corso è inserito nel Programma Nazionale di Educazione Continua in Medicina del Ministero della Salute n. ID 5928 265881, accreditato con n° 6 crediti formativi per i profili professionali del Medico chirurgo (tutte le discipline previste dalMinistero della Salute), del Farmacista (Territo- riale e Ospedaliero), Psicologo, Veterinario e Odontoiatra.

L’ ingresso è gratuito con registrazione obbligatoria.

Sede dell’evento:

Hyatt Centric, Milano Centrale
Via Giovanni Battista Pirelli, 20
20124 Milano

Telefono: 02 8989 1234



July 20, 2019 EventiUncategorized

L’associazione Polisportiva Arnasco in collaborazione con IMBIO (Istituto di Medicina Biologica)
sono lieti di invitarvi alla serata divulgativa sul tema dell’infiammazione

Infiammazione: come riconoscere, curare e prevenire.

L’evento gratuito ad ingresso libero si terrà stasera, Sabato 20 luglio 2019 alle h 20:30
presso presso l’ Auditorium San Carlo in via Roma, 70 di Albenga (SV).

 

POLISPORTIVA ARNASCO FARMACIA DOTT. MARCO ROGLIATTI

PROF. GIUSEPPE DI FEDE – RELATORE

Medico Chirurgo Specialista in Nutrizione Dietetica Clinica Medicina Preventiva e Genetica
Docente di Nutrigenomica e Nutrizione Umana -Università di Pavia Direttore Sanitario Istituto di Medicina Biologica e dell’Laboratorio IMBIO

DOTT. MARCO ROGLIATTI – MODERATORE

Farmacista Esperto in Alimentazione ed Integrazione nello Sport

Ingresso gratuito

Per informazioni
Cell. +39 340 232 3159 



Per un fisico funzionale ed atletico è imprescindibile un assetto ormonale armonico e bilanciato.

A tal fine, un alimentazione che assecondi il fisiologico funzionamento degli ormoni, associata ad una attività fisica anche di scarsa intensità, risulta essere la chiave di volta nel raggiungimento dell’ obbiettivo.

Gli “ormoni target” di questo particolare regime alimentare sono:

  • Insulina: ormone prodotto dal pancreas, se in eccesso favorisce l’accumulo di massa grassa.
  • Cortisolo: ormone prodotto dal surrene, se non ben bilanciato favorisce l’ accumulo di massa grassa e la riduzione della massa muscolare

La  “DIETA ORMONALE” garantisce un controllo efficiente di questi due ormoni e si basa su un semplice principio: assumere carboidrati e proteine in momenti distinti della giornata.

Aggiungendo pochi altri accorgimenti è infine possibile individuare quattro punti cardine per delineare un piano nutrizionale che favorirà il tanto  desiderato ventre piatto ed un funzionamento dell’ organismo ottimale.

  1. COLAZIONE BILANCIATA: Inserire sempre nella colazione una fonte proteica (affettato, salmone, uova, yogurt greco, frutta secca…) accompagnato ad una fonte di carboidrati (fette biscottate integrali, fette wasa, un frutto…) e una fonte di grassi buoni (avocado, frutta secca…)
  1. 5 PASTI AL GIORNO: suddividere l’introito calorico giornaliero in 5 pasti: colazione, pranzo, cena e due spuntini (metà mattina e metà pomeriggio). Si consiglia un frutto fresco di stagione a metà mattina e un pugno di frutta secca con una noce di parmigiano a metà pomeriggio
  1. PRANZO A BASE DI CARBOIDRATI: i pranzi consigliati si basano su un carboidrato a basso indice glicemico (pasta integrale, riso integrale, farro…) + verdure di stagione + olio extravergine di oliva.
  1. CENA A BASE DI PROTEINE:per cena si consiglia una fonte proteica (uova, pesce, carne bianca…) + verdure di stagione + olio extravergine di oliva.

Questo piano alimentare si basa quindi su una colazione “mista” carboidrati e proteine, carboidrati a metà mattina e pranzo, proteine a metà pomeriggio e cena.

Per ottenere risultati ottimali è sempre consigliabile rivolgersi ad uno specialista, che saprà valutare e consigliare il piano nutrizionale più adatto alle vostre esigenze.
Rivolgiti al nostro studio per una consulenza personalizzata!

segreteria@imgep.com
Tel. 02 5830 0376


Si è sempre considerata la risposta infiammatoria come se fosse un tutt’uno, oggi però si possono identificare due tipologie di infiammazioni con genesi differenti: una di tipo macrofagica e una di tipo linfocitaria.

L’infiammazione macrofagica, ovvero quella più antica e ancestrale, si traduce nella produzione di interleuchina 6, interleuchina 1 beta e TNF alfa, le quali sono globalmente concomitanti.
Questo tipo di infiammazione tende ad essere prevalente nei tumori. Invece l’altro tipo di infiammazione ha origine linfocitaria e in particolare in una sottospecie di linfociti T, ovvero i TH17, i quali producono la interleuchina 17 (potentemente infiammatoria) la quale è in grado di indurre una risposta infiammatoria più evoluta e quindi più efficace; agisce inibendo i linfociti T regolatori i quali sono per definizione i linfociti antinfiammatori.
Per cui, per sommatoria algebrica, inibizione più inibizione porta allo scatenamento della malattia autoimmune.

Riassumendo esistono due tipi di infiammazione: una più antica, di tipo macrofagica, che si traduce nella produzione di citochine, in cui è attiva l’IL 6, ovvero quella che dà la febbre, lo stato settico, la vasodilatazione; la seconda consiste nella produzione della IL 17, prodotta dai TH17 la quale attiva una risposta infiammatoria inibendo i linfociti T-REG.
La IL 17 è la principale interleuchina coinvolta nella patologie autoimmuni.

A Preliminary Study on the Correlation between Il-6 And Il-17 Secretions in Human Systemic Diseases: Possible Existence of Two Different Origins of the Inflammatory Response

Lissoni P, et al. Clin Oncol Res J: CORJ-100004



Pancia gonfia, stipsi o colite, rinite, orticaria e dermatite, sembra ormai essere la regola in questo periodo dell’anno.
Sono sintomi da ricondurre a reazioni allergiche, o a intolleranze alimentari caratteristiche di questa stagione.
Spesso gli esami specifici per la ricerca della allergie tradizionali non danno una risposta.

E se si trattasse di reazioni allergiche ritardate causate da intolleranze alimentari?
Spesso sono dovute ad accumulo di sostanze liberatrici di istamina o contenenti istamina ( sostanza che crea i sintomi delle allergie). I sintomi e le reazioni sono sovrapponibili nei due casi, ma la diagnosi si basa su test diversi.

Un prelievo di sangue per eseguire il test ALCAT®, ci aiuterà a scoprire quali alimenti o conservanti alimentari sono causa di reazioni infiammatorie da cibo, che causano reazioni istaminiche con i relativi sintomi.
Una volta individuato il gruppo di alimenti, il medico o biologo specialista in alimentazione ed esperto di gestione delle intolleranze alimentari, sarà in grado di consigliare un programma alimentare adeguato, con esclusione in una prima fase degli alimenti risultati positivi al test, seguita da una seconda fase di reintroduzione degli alimenti esclusi a rotazione, in modo da non sovraccaricare l’organismo di istamina.

I benefici di un programma alimentare ad esclusione degli alimenti reattivi e successiva reintroduzione, sono molti, inizialmente si perdono liquidi in eccesso, poi si verifica un moderato calo di peso, migliora la reattività globale dell’organismo ritrovando l’energia persa, ma soprattutto si ha un miglioramento complessivo dei sintomi allergici.
Sotto la guida esperta di un medico o biologo nutrizionista è possibile proseguire il programma alimentare anche oltre il periodo delle allergie, per mantenere i benefici ottenuti in precedenza.

Guarire dalle intolleranze alimentari è possibile seguendo un programma nutrizionale adeguato e specifico per le proprie esigenze e problematiche allergiche o da intolleranze.

Per ricevere maggiori informazioni:
segreteria@imgep.com
Tel. 02 5830 0376


May 20, 2019 Uncategorized

La tiroide è un organo piccolo,  ma fondamentale e coinvolto in diverse funzioni vitali del nostro organismo.
Gli ormoni prodotti da questa ghiandola agiscono ad esempio sulla funzionalità cardiovascolare, sul ritmo del sonno, sul metabolismo osseo  e  sul sistema nervoso.
È molto importante prendersi cura di quest’ organo!

Dal 20 al 26 maggio IMBIO Lab promuove la salute e la prevenzione della tiroide, offrendo ad un prezzo speciale il pacchetto per il check up completo.

Potrai effettuare l’esame direttamente presso il nostro laboratorio
IMBIO Lab
via Sidoli , 1 MILANO
da lunedì a sabato dalle 8-11

Contattaci subito per ricevere maggiori informazioni: 
segreteria@imgep.com
Tel. 02 5830 0376


Un nuovo studio, presente su PUBMED e pubblicato a Marzo su Alternative Therapies in health and medicine, correla un risultato positivo del test ALCAT® agli zuccheri fruttosio, canna da zucchero barbabietola da zucchero, alla mutazione del gene TCF7L2, legata all’insulino-resistenza e alla predisposizione al diabete di tipo II.

La resistenza all’insulina (RI) è definita come l’incapacità di una quantità nota di insulina esogena o endogena di aumentare l’assorbimento e l’utilizzo del glucosio. Diversi meccanismi sono stati proposti come possibili cause alla base dello sviluppo della RI e della sindrome RI. La resistenza insulinica fa parte di un gruppo di anomalie metabolico-cardiovascolari comunemente note come “Sindrome metabolica”. Essa può portare allo sviluppo di diabete di tipo 2, aterosclerosi, ipertensione, dismenorrea, irsutismo e sindrome dell’ovaio policistico, a seconda del background genetico del singolo individuo. Lo scopo di questo studio è stato quello di valutare, in 123 donne e 35 maschi (età media, 42 y ± 10.3, range 19-75 y) volontari se la resistenza insulinica potesse essere in parte correlata ad un’intolleranza allo zucchero nella dieta e se ci potesse essere una correlazione tra il test di intolleranza ALCAT e una mutazione del gene TCF7TL2 . Tale gene promuove infatti la trascrizione del proglucagone e svolge un ruolo chiave nello sviluppo delle isole di Langherans. I risultati hanno evidenziato, in maniera statisticamente significativa, che i soggetti con intolleranza allo zucchero presentano anche un’alterazione (completa o parziale)  del gene TCF7TL2. Sulla base di questi risultati, il nostro studio ha dimostrato che esiste una correlazione clinica tra il test di intolleranza alimentare ALCAT e la resistenza insulinca. La positività al test ALCAT di uno degli zuccheri testati (fruttosio, canna da zucchero e barbabietola da zucchero) indica, nella maggior parte dei soggetti, la presenza di una mutazione del gene TCF7L2 e potrebbe contribuire alla prevenzione e al trattamento della RI.

Leggi l’articolo originale su Pub Med

Altern Ther Health Med. 2019 Mar;25(2):22-38.

Pompei PGrappasonni IScuri SPetrelli FTraini ESorrentino SDi Fede G.


cartolina-evento-sarzana-fronte.jpg

March 14, 2019 Eventi

Sabato 13 aprile 2019, dalle h 15:30 a Sarzana (SP)
presso Sala Consiliare del Comune di Sarzana in Piazza Matteotti, 1
si terrà la giornata divulgativa dedicata al rapporto tra il cibo e le reazioni del corpo:

“E adesso, cosa mangio? Capire e gestire le reazioni avverse ai cibi”

Imbio parteciperà con il Direttore Sanitario Prof. Giuseppe Di Fede,

Il Professore parlerà di allergie e intolleranze, con un approccio moderno orientato al paziente e soluzioni.

La Dott.ssa Ilaria Sagliano – Marina di Carrara (Biologa Nutrizionista) ed il Dott. Franco Aliboni – Sarzana (Biologo Nutrizionista Specialista in Scienza dell’Alimentazione) svilupperanno in modo semplice il tema dell’infiammazione da cibo e l’importanza della varietà e rotazione dei cibi, degli additivi presenti nei cibi che possono causare infiammazione.
Al termine dell’incontro ci sarà spazio per discutere insieme tutte le domande e i dubbi che il pubblico vorrà porre.

L’evento, organizzato in collaborazione con Alimentazione Futura.it e LAM (Laboratorio di Analisi Mediche di Sarzana) è gratuito e ha già catturato l’attenzione della stampa.

Per info e prenotazioni tel. 02 58300 376  oppure segreteria@imgep.com

Vi aspettiamo!



Non-Celiac Gluten Sensitivity in patients with severe abdominal pain and bloating: The accuracy of ALCAT 5

Background and aims: Non-Celiac Gluten Sensitivity (NCGS) is a recently proposed clinical condition causing both intestinal and extra-intestinal symptoms, without gastrointestinal lesions, which improve on avoiding gluten intake, in the absence of celiac disease and wheat allergy. The prevalence of this condition is still a matter of debate, in part due to the very recent introduction of an accepted diagnostic test, a double-blind, placebo controlled gluten challenge. However, this is a lengthy and cumbersome procedure, theoretically burdened by a significant reduction of patient compliance. ALCAT 5 is an automated in vitro test evaluating the toxic effect of gluten on neutrophils by the exposure of these cells to a gluten-containing extract of gluten-containing cereals. The test is very simple to perform, the results are rapidly obtained, and might represent, if sufficiently accurate, a promising alternative to diagnose gluten intolerance. The aim of this study was the comparison of ALCAT 5 results with those of a double- blind, placebo-controlled, gluten challenge, in a group of patients with clinically-suspected NCGS. Methods: Twenty-five patients (M/F 3/22, mean age 32 ± 4 yrs) with severe functional abdominal pain and bloating, who had previously undergone the ALCAT 5 test, were enrolled. All the subjects reported their symptoms on a gluten-containing diet and considered gluten the causal agent. Following the Salerno Experts’ Criteria, they underwent a double-blind, placebo controlled trial with gluten vs placebo. A mean value during gluten ingestion >30% of the value during placebo was considered as indicative of gluten sensitivity.

Results: After blinded administration of gluten, 13 out of 25 (52%) patients showed an increase in the severity of abdominal pain, and 11 out of 25 (44%) showed an increase in the severity of abdominal bloating. Considering these two symptoms together, in 16 patients out of 25 (64%), blinded gluten administration induced an increase of abdominal pain and/or bloating. The ALCAT 5 test proved to be positive in 20 and negative in 5 patients. In sixteen patients out of 25 the result of ALCAT 5 agreed with the double-blind trial (64%). In particular, both tests were positive in 14 patients and negative in 2. Conclusions: In this subgroup of patients, ALCAT 5 could be used to support the clinical suspicion of the presence of NCGS and to address these patients to a blinded gluten challenge.

Introduction

Non-Celiac Gluten Sensitivity (NCGS) is a recently proposed clinical condition causing both intestinal and extra-intestinal symptoms which improve on avoiding gluten intake, in the absence of gastrointestinal lesions, celiac disease and wheat allergy. The prevalence of this condition is still a matter of debate. The first descriptions of NCGS were characterized by very high fre- quency reporting [2], but recently more realistic figures were described [3,4]. This discrepancy may be explained by the recent introduction of an accepted diagnostic test, a double-blind, placebo controlled gluten challenge [5], whereas the patient merely self- reporting the causative relationship between gluten ingestion and symptom occurrence was previously considered sufficient to diagnose the condition [6]. Apart from some criticisms on the interpretation of the results of the double-blind, placebo controlled food challenge, the proposed gluten challenge seems very prom- ising to describe the real prevalence of this condition. However, it is a lengthy and cumbersome procedure, theoretically burdened by a significant reduction in patient compliance during the three weeks of substrate intake.

ALCAT 5 is an in vitro test evaluating the toxic effect of gluten on neutrophils by the exposure of these cells to a gluten-containing extract of gluten-containing cereals, i.e., wheat, rye, barley, and oats. Results of the test are obtained through an automated mea- surement of neutrophil size and volume modifications following their incubation with gluten-containing cereal extracts [7]. The test is considered positive when the automated analysis reveals, in com- parison with the basal value, a change in volume and shape of neu- trophils after exposure to a test food substance. The test data are expressed as a volume distribution curve and the mean ± SD modi- fication of the area under the curve, in comparison with basal volume, is considered positive. An area change between the mean volume and 1 SD is considered positive. The test is very simple to perform, the results are rapidly obtained, and might represent, if sufficiently ac- curate, a promising alternative to diagnose gluten intolerance.

The aim of this study was the comparison of ALCAT 5 results to those of double-blind, placebo-controlled, gluten challenge, in a group of patients with suspected NCGS, in order to evaluate the performance of this test.

2. Patients and methods

Twenty-five patients (22 females, mean age 32 ± 4 yrs) with a long history of abdominal symptoms were enrolled. All the patients reported their symptoms on a gluten-containing diet, considered gluten to be the causal agent, and judged bloating and abdominal pain as the most severe. These characteristics of symptoms were confirmed by the completion of a questionnaire, based on a visual analogue scale, before entry the study. The mean duration of these two main symptoms were 10 ± 4 yrs. In all the patients, the pres- ence of organic conditions was excluded by endoscopic or radio- logic procedures, routine blood tests including thyroid function tests, coeliac disease associated serology, and abdominal ultra- sound. None of the patients suffered from wheat allergy. In this group of patients the following diagnoses were previously made: functional dyspepsia (n 1⁄4 14), irritable bowel syndrome (n 1⁄4 18), functional bloating (n 1⁄4 12), functional diarrhoea (n 1⁄4 8), functional constipation (n 1⁄4 6). In individual patients, more than one diag- nosis was frequently made. Rome IV criteria for functional bloating proved to be positive for all the patients, but for all the other conditions a positivity was present in only six patients (5 females, one male; 1 irritable bowel syndrome with constipation, 2 func- tional constipation, 1 irritable bowel syndrome with diarrhoea, 2 functional diarrhoea) [8,9].

All the patients underwent the ALCAT 5 test in the 3 months before the study on gluten-containing diet. However, the results of this test were blinded to the investigators during the next phases of the study. During the period from the ALCAT 5 test to the study entry, patients followed a gluten-containing diet.

None of the patients was following therapy known to interfere with intestinal function during the month prior to the study, such as antibiotics, prokinetics or laxatives. Constipated patients were advised to use a gentle water enema when needed and, in patients with diarrhoea, loperamide was allowed, if strictly necessary.

The protocol was approved by the local Ethical Committee and all the subjects gave their written informed consent.

2.1. NCGS diagnosis

Before the beginning of the study, and after ALCAT 5 test, all the patients had followed a period of gluten-free diet (GFD) which was even longer than the 6-week period suggested by the Salerno protocol [5], and all declared a clear improvement of symptom severity. Accordingly, we decided to avoid the repetition of this phase. However, to avoid an effect of gluten ingestion during the days immediately before the beginning of the protocol in sensitized patients, we prescribed a 2-week period of GFD, as a run in period, followed by the 3-week period of the blinded procedure suggested by the Salerno protocol [5], composed of two weeks of capsule ingestion, separated by one week of wash-out period (Fig. 1). After the run in period, the patients continued a strict GFD and were asked to fill in a daily questionnaire to rate the severity of both intestinal and extraintestinal symptoms, considered as gluten- dependent in NCGS (Table 1). Then, in a random order, following a randomization list generated by a computer, the patients were selected to follow a one week period during which gluten (10 capsule/day, 500 mg/capsule) or placebo capsules (rice starch, 10 capsule/day, 500 mg/capsule) were ingested. Rice starch was cho- sen due to its rapid absorption in comparison with other complex carbohydrates. At the end of the first week of capsule ingestion, the patients followed a 1-week wash-out period, without taking cap- sules, but continuing the completion of the daily questionnaires. Then, at the end of the wash-out period, the second period of capsule intake began (Fig. 1).

The daily questionnaire was administered to evaluate the presence and severity of abdominal and extra-intestinal symptoms, indicated in Table 1. The questionnaires used a 100 mm-long visual analogue scale (VAS) and patients were instructed to indicate the severity of each symptom on the line, considering the left end of the line as “absence of symptom” and the right end as “severe symp- tom” [10]. The score of the symptom was calculated by the sum of the score of the single days of each week. In accordance with the Salerno criteria, a mean value of the severity of abdominal pain and bloating during gluten ingestion >30% the value during placebo was considered as indicative of NCGS.

2.2. Statistics

To evaluate agreement between the gold standard test for NCGS and ALCAT 5 we used Cohen’s k. We judged the extent of the agreement according to Landis and Koch [11]. Agreement was considered: poor if k < 0.00; slight if 0.00 k 0.20; fair if 0.21
k 0.40; moderate if 0.41 k 0.60; substantial if 0.61 k 0.80; almost perfect if k > 0.80. Additionally, we calculated the sensi- tivity, specificity, and positive and negative predictive values of ALCAT 5: for these calculations we considered a subject to be positive if she/he displayed a worsening in pain or bloating at the blinded administration of gluten.

3. Results

After blinded administration of gluten, 13 out of 25 patients showed an increase in the severity of abdominal pain >30% than after placebo capsules (52%), and 11 out of 25 showed an increase in the severity of abdominal bloating >30% than after placebo cap- sules (44%).

Alcat Results

Alcat 5Considering symptom severity after gluten challenge, in the whole group of patients we found a significant correlation between the severity of abdominal pain and abdominal bloating (r 1⁄4 0.64, p < 0.0005) (Fig. 2), and between the modification of abdominal pain and the modification of bloating (r 1⁄4 0.54, p < 0.005) (Fig. 3).

Among the other symptoms we included in the questionnaire, none of the extraintestinal symptoms worsened after gluten chal- lenge (data not shown). Gluten challenge worsened the severity of

flatulence in 11 patients, the severity of nausea in 4 patients, the severity of diarrhoea in 1 patient, and the severity of borborygmus in 1 patient. The number of bowel movements and the Bristol score during gluten challenge were not significantly different than pla- cebo challenge.

ALCAT 5 test proved to be positive in 20 and negative in 5 pa- tients. The comparison between ALCAT 5 and blinded gluten challenge results showed the two tests were concordant in 12 out of 25 patients (48%) when we considered abdominal pain as the main symptom and in 13 out of 25 patients (52%) when we considered bloating as the main symptom. However, the concordance of the two tests improved if the modification of both symptoms was considered: in 16 out of 25 patients (64%) the severity of at least one of the two symptoms during gluten capsule intake was >30% than its severity during placebo capsule intake. In this case, ALCAT 5 and blinded gluten challenge results were concordant in 16 out of 25 patients (64%).

We also evaluated the agreement between the two tests. The agreement between the ALCAT 5 and positive pain symptoms after blinded gluten administration was poor (Cohen’s k 1⁄4 0.06). The agreement between the ALCAT 5 and positive bloating symptoms after blinded gluten administration was slight (Cohen’s k 1⁄4 0.03). Similarly, if we considered positive pain or bloating symptoms after blinded gluten administration, agreement between the two tests was slight (Cohen’s k 1⁄4 0.04).

The ALCAT 5 has a sensitivity of 81% but a poor specificity of 22.2%. The positive predicted value (PPV) of the ALCAT 5 was 65%, while the negative predicted value (NPV) was 40%.

Alcat 5 test

Alcat 5

4. Discussion

Whether symptoms attributed to NCGS are indeed due to gluten intake is still a matter of debate [12]. On pathophysiological grounds, this is a very important topic, as the exact definition of the main actor inducing symptom onset in this condition will allow for a specific treatment. Accordingly, it is important to clarify whether gluten or wheat [13] should be the target of our attention, but also FODMAPs [14] or amylase-trypsin inhibitors [15]. Consequently, the same uncertainty is also present on diagnostic grounds. As far as the role of gluten is concerned, a double-blind, placebo-controlled, gluten challenge was recently proposed [5]: resembling that already adopted in the diagnostic algorithm of food allergy, a blinded administration of gluten or placebo together with a strict symptom occurrence monitoring is today considered an accurate test to diagnose NCGS. We and others [3,4] have recently applied this protocol in patients self-reporting the gluten dependence of their symptoms and some drawbacks should be reported. First of all, the protocol suggests a preliminary 6-week period of GFD to evaluate if symptom improvement may be achieved, to select the subgroup of patients who need a blinded gluten challenge. Since this preliminary phase is unblinded, it is possible that a placebo or nocebo effect may have a role in the improvement of symptoms. The length of this period might be responsible for an excessive extension of the whole protocol and, therefore, it could reduce the patient’s compliance. Second, the organoleptic characteristics of gluten make true blindness very difficult: it must be not visible to the patients and, therefore, it must inevitably be hidden in capsules. Moreover, to avoid excessive capsule size, due to the physical characteristics of gluten, a maximum amount of 500 mg can be contained in one capsule and this causes the need for a high number of capsules to be ingested in a day in order to administer a dose of gluten sufficient to induce symptoms. The ingestion of 10 capsules a day for two weeks, one for the gluten test and the other for the placebo test, i.e. 140 capsules in total, might cause a reduction in patient compliance. Third, daily questionnaires for symptom occurrence monitoring administered over many days might cause a reduction of the patient’s attention, in particular during the last period of the test. Consequently, it is evident that, even if the blinded food challenge is considered the gold standard

in the diagnosis of many adverse reactions to food [16], this test is largely absent in a clinical setting [17].

Accordingly, the availability of alternative tests is advisable. ALCAT 5 is a simple, automated test that could represent a valid option in the diagnosis of NCGS. This is the first evaluation of the accuracy of ALCAT 5 in human disorders: the principle of the test is derived from the ALCAT test, adopted for food intolerance [7], and it was applied to discriminate the role of gluten in self-reported NCGS patients.

Our results show that in a group of patients suffering in particular from functional severe abdominal pain and bloating and without organic diseases, wheat allergy or celiac disease, the prevalence of NCGS is higher than previously reported [3,4], sug- gesting that, in a gastroenterological outpatient clinic, abdominal symptoms are more indicative than extra-intestinal symptoms to guide physicians towards a correct diagnostic algorithm for this condition. All the enrolled patients have previously undergone the ALCAT 5 test, and the comparison between ALCAT 5 and blinded gluten challenge showed that in 64% of cases a concordance was evident. The concordance between the two tests was less accurate when abdominal pain or bloating were considered separately. However, the strict correlation between postechallenge severity of these two symptoms permits the adoption of a combination of them, thus optimizing the performance.

The assessment of the degree of agreement between the double blinded gluten challenge and ALCAT 5 tests showed very low values of Cohen’s k. Considering the single symptoms separately or together, results indicate that the agreement between the tests was no better than would be expected by chance. However, these results are similar to those obtained from a faecal occult blood test and a colonoscopy for the screening of left-sided colon cancer [18,19]. Accordingly, the importance of our results relies on the possibility of using the ALCAT 5 test preliminary to the blinded gluten chal- lenge. Due to the complexity of clinical manifestations of NCGS, frequently characterized by many concomitant symptoms, both intestinal and extraintestinal [2], as often reported by the patients, it may be difficult in many of them to correctly focus on the de- scriptions and the importance of any single symptom during the interpretation of the whole clinical presentation. Therefore, ALCAT 5 might be used to preliminarily screen patients with severe abdominal pain and bloating in order to select, in this subgroup of References patients, which of them should undergo the blinded gluten challenge, at least on the basis of these two main symptoms.

A limit of the study was the absence of a healthy control group, to test for in vitro modification of neutrophils after oral gluten challenge. In a subsequent study, it should be important to test for this modification and to evaluate also the reproducibility of the procedure.

In conclusion, we have compared ALCAT 5 and double-blind, placebo-controlled, gluten challenge results in a group of self- reported NCGS with severe abdominal pain and bloating, to eval- uate if a simplification of diagnostic procedures is possible in these patients. In this subgroup of patients, ALCAT 5 could be used to support the clinical suspicion of the presence of NCGS and to direct these patients to a blinded gluten challenge.

Conflict of interest
The authors have no conflict of interest to declare.

Funding sources

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Guarantor of the article

Michele Di Stefano.

Specific author contributions

Michele Di Stefano planned and conducted the study, inter- preted data, drafted the manuscript.

Eugenia Vittoria Pesatori, Giulia Francesca Manfredi, Giacomo Grandi, Alessandro Gabriele, Davide Iozzi conducted the study, collected and interpreted data, drafted the manuscript.

Mara De Amici conducted the study, collected data and drafted the manuscript.

Giuseppe Di Fede planned the study and drafted the manuscript.

All the mentioned Authors approved the final version of the manuscript.

Acknowledgements

None.

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