|Year : 2020 | Volume
| Issue : 2 | Page : 300-306
Assessment of lactose intolerance in adult Egyptian patients with dyspeptic symptoms using lactase enzyme assay in duodenal biopsy
Mona Ramadan1, Alshimaa M. M Eid1, Nora M.A Seliem2, Heba A.A Shokr3
1 Department of Hepatogastro-Enterology and Infectious Diseases, Faculty of Medicine for Girls, Al Zahraa University Hospital, Cairo, Egypt
2 Department of Biochemistry, Faculty of Medicine for Girls, Al Zahraa University Hospital, Cairo, Egypt
3 Department of Hepatogastroenterology and Infectious Disease, Medical Administration for Girls, Al Zahraa University Hospital, Cairo, Egypt
|Date of Submission||30-Apr-2020|
|Date of Decision||16-May-2020|
|Date of Acceptance||19-May-2020|
|Date of Web Publication||29-Jun-2020|
MD Alshimaa M. M Eid
Lecturer of Hepatogastroenterology and Infectious Disease, Al Zahraa University Hospital, Al- Mokattam, Street 9, Building no. 7084 – Second Floor, ZIP/Postal Code: 11571
Source of Support: None, Conflict of Interest: None
Objective To assess the role of endoscopic duodenal biopsies in diagnosing lactose intolerance of adult Egyptian patients with dyspeptic symptoms.
Patients and methods A validated self-administered questionnaire was applied on 200 patients for symptom assessment after ingestion of lactose or lactose products. They are referred to the Hepatogastro-enterology and Infectious Diseases Department of Al-Zahraa University Hospital during the period from December 2018 to December 2019. Forty adult patients out of 200 were selected and subjected to history taking, clinical, laboratory evaluation, stool analysis, and abdominal ultrasound. They underwent upper gastrointestinal (GI) endoscopy and two postbulbar duodenal biopsies were taken for histopathology and biochemical assay of the lactase enzyme.
Results The symptom questionnaire of 200 patients after ingestion of lactose-containing products showed that the mean and SD score of flatulence was the highest score (5.69±0.24); abdominal cramping was 3.29±0.16 while diarrhea was 0.84±0.09 and vomiting was the lowest score (0.30±0.05). Forty patients were selected for upper GI endoscopy with a mean age of 35.15±12.14 years; of the patients, 70.0% were women and 30.0% were men There was no statistically significant results as regards laboratory data or abdominal ultrasound. According to the values of lactase enzyme level in duodenal biopsies; 65% of patients had mild hypolactasia compared with 35% who were constant with normo lactasia and no patients with severe hypolactasia.
Conclusion Adult patients with lactose intolerance mainly complain of abdominal cramps and flatulence more than other GI tract symptoms. Biochemical assay of lactase enzyme 35% who were constant with normolactasia and no patients with severe hypolactasia.
Keywords: biochemical lactase assay, lactase enzyme, lactose intolerance
|How to cite this article:|
Ramadan M, Eid AM, Seliem NM, Shokr HA. Assessment of lactose intolerance in adult Egyptian patients with dyspeptic symptoms using lactase enzyme assay in duodenal biopsy. Sci J Al-Azhar Med Fac Girls 2020;4:300-6
|How to cite this URL:|
Ramadan M, Eid AM, Seliem NM, Shokr HA. Assessment of lactose intolerance in adult Egyptian patients with dyspeptic symptoms using lactase enzyme assay in duodenal biopsy. Sci J Al-Azhar Med Fac Girls [serial online] 2020 [cited 2020 Oct 23];4:300-6. Available from: http://www.sjamf.eg.net/text.asp?2020/4/2/300/288287
| Introduction|| |
Lactose intolerance is a diffuse gastrointestinal (GI) symptom after intake of milk and dairy products, usually due to impaired production of the enzyme lactase-phlorizin hydrolase in the intestinal epithelial cells . The production of lactase enzyme is genetically determined to cease after weaning or during childhood in a condition termed lactase nonpersistence. Lactase persistence, by contrast, is characterized by a sustained lifelong production of the enzyme .
About two-thirds of the world’s population undergo a genetically programmed decrease in lactase synthesis after weaning (primary lactase deficiency) . The term hypolactasia refers to the deficiency of the lactase enzyme; this leads to lactose malabsorption, which is an inefficient digestion of the disaccharide, which, in turn, can lead to lactose intolerance lactase nonpersistence .
Additionally, in individuals with lactase persistence, the occurrence of GI infection, inflammatory bowel disease, abdominal surgery, and other health issues can also cause a decrease in lactase activity (secondary lactase deficiency). Symptoms suggestive of lactose intolerance are nonspecific such as abdominal pain, bloating, flatulence, and diarrhea .
Testing of lactase activity in mucosal biopsies from the duodenum is regarded as the reference standard for primary and secondary lactase deficiency .
Lactose digestion can also be assessed by the lactose tolerance test, the H2-breath test, genotyping, using a new real-time PCR assay, and small intestinal biopsy .
| Aim|| |
To assess the role of endoscopic duodenal biopsies in diagnosing lactose intolerance in adult Egyptian patients with dyspeptic symptoms.
| Patients and methods|| |
This is a cross-sectional study that was conducted on 200 adult Egyptian patients referred to Hepatogastroenterology and Infectious Diseases Department of Al-Zahraa University Hospital with dyspeptic symptoms after ingestion of lactose or lactose-containing products during the period from December 2018 to December 2019.
A validated self-administered questionnaire for lactose intolerance was used for symptom assessment. The questionnaire includes five items reported by lactose-intolerant patients (diarrhea, abdominal cramping, vomiting, audible bowel sounds, and flatulence).
From those 200 patients, 40 adult Egyptian patients underwent upper endoscopy and two pinch biopsies were taken from the second duodenal part. Biochemical assay of the lactase enzyme level was done in these biopsies.
Adult patients with dyspeptic symptoms after ingestion of lactose and dairy products such as chronic diarrhea, abdominal pain, nausea, bloating, and flatulence.
Patients with contraindication for upper GI endoscopy, history of bleeding disorder, features of malignancy, and diabetic or hepatic patients. Patients with inflammatory bowel disease or taking PPI or NSAIDs 15days before the endoscopy.
All patients (40) included in this study were subjected to history taking, stool analysis, clinical, laboratory evaluation (CBC, LFTs, KFTs), and abdominal ultrasound.
Then upper GI endoscopy was done using conventional white light endoscopy. Macroscopic evaluation and two postbulbar duodenal biopsies were taken and was sent for biochemical assessment of lactase enzyme and for histopathological examination.
Biochemical lactase enzyme assessment: biochemical lactase assessment in two endoscopic duodenal biopsies tissue homogenate was done, each was 10 mg. The specimen was preserved in purified sample homogenization buffer. Certain volume of PBS (pH 7.4) was added and rapidly frozen with liquid nitrogen till the time of melting. After melting, store samples at 2–8°C. Add a certain volume of PBS (pH 7.4), homogenize thoroughly, and centrifuge at a speed of 2000–3000.
Principle of the assay: this kit was based on standard sandwich enzyme-linked immunosorbent assay technology. Manual instructions were performed. Calculation of lactase enzyme activity results were assessed (U/g) from blotted standard curve.
According to the values of lactase enzyme level in duodenal biopsies: values less than 10 U/g indicate severe hypolactasia, values 10–30 U/g indicate mild hypolactasia while values more than 30 U/g indicate normolactasia . So, the patients were then divided into group I with mild hypolactasia and group II with normolactasia.
Ethical consideration: the protocol of the study was approved by the Institutional Review Board and Ethics Committee of Faculty of Medicine for Girls AL-Azhar University. IRP no (202001088) and informed consent was obtained from each patient participating in this study after explanation of the objectives and benefits of the study.
Recorded data were analyzed using the Statistical Package for Social Sciences, version 23 (IBM SPSS) (Corporate headquarters: 1 New Orchard Road Armonk, New York 10504-1722, United States of America). Quantitative data were expressed as mean±SD. Qualitative data were expressed as frequency and percentage.
| Results|| |
[Table 1] and [Table 2] show that the main symptoms after ingestion of lactose-containing products were flatulence with mean±SD 5.69±0.24, followed by abdominal cramping (3.29±0.16) while diarrhea was 0.84±0.09.
|Table 1 Frequency of lactose-containing food questionnaire among the studied patients with related gastrointestinal tract symptoms (200 patients)|
Click here to view
|Table 2 Results of the symptoms questionnaire after ingestion of lactose and lactose-containing products (200 patients)|
Click here to view
The 40 studied patients were with a mean age of 35.15±12.14 years. There were 70.0% women and 30.0% were men. The mean of their BMI was 29.06±5.87.
According to [Table 3] , we classified our patients into two groups:
- Group I: who had mild hypolactasia (26 patients) (65%).
- Group II: patients with normolactasia (14 patients) (35%).
|Table 3 Lactase enzyme level in duodenal biopsy among the studied patients (40)|
Click here to view
[Table 4] shows no statistically significant difference as regards age, sex, and BMI between both groups.
|Table 4 Relation between age, sex, and BMI and lactase enzyme level among the studied groups|
Click here to view
[Table 5] shows statistically significant difference concerning abdominal cramping and flatulence between both groups with a P value of 0.010 and 0.014, respectively.
|Table 5 Comparison between both groups as regards gastrointestinal tract symptoms of lactose intolerance|
Click here to view
[Table 6] shows statistically significant difference in perceiving symptoms after ingestion of regular milk between both groups with a P value of 0.031.
|Table 6 Comparison between both groups as regards the type of food ingested|
Click here to view
[Table 7] shows no statistically significant difference in histopathological findings of the upper endoscopic biopsies between both groups.
|Table 7 Comparison between the histopathological findings of the upper endoscopic biopsies between both studied groups|
Click here to view
[Table 8] shows that there was significant negative correlation between (abdominal cramping and flatulence) and lactase enzyme level in the studied groups.
|Table 8 Correlation study between lactase enzyme level and other parameters in the studied groups|
Click here to view
| Discussion|| |
Lactose intolerance is a common disorder and is due to the inability to digest lactose into its constituents, glucose and galactose, secondary to low levels of lactase enzyme in the brush border of the duodenum .
The current study included 200 adult Egyptian patients complaining of dyspeptic symptoms related to ingestion of lactose and dairy products. They were randomly selected from Hepatogastro-enterology and Infectious Diseases Department, Al-Zahraa University Hospital. All the patients underwent a questionnaire for different lactose-containing food and related symptoms.
Our study showed that about 40.0% of patients suffering after ingestion of regular milk, about 33.0% after ingestion of reduced fat milk, and about 16.0% suffering after ingestion of cheese, and different percent of other products. Also, our study showed that there was statistically significant difference in perceiving symptoms after ingestion of regular milk between both mild hypolactasia and normolactasia groups with a P value of 0.031 and no statistically significant difference between the two studied groups regarding other lactose-containing products.
There is considerable interindividual variability in the severity of symptoms, according to the amount of lactose ingested. In this regard, a single dose of lactose of up to 12 g administered alone produces no or minor symptoms in persons with lactose intolerance or maldigestion, while doses of 15–18 g are well tolerated when offered together with other nutrients. With doses larger than 18 g, intolerance becomes progressively more frequent .
Lactose is also present in cultured milk products such as yoghurt and cheese. Yoghurt contains ≈50% of the lactose of unprocessed milk, whereas, cheese has low lactose content . Valid evidence is missing for a relationship between symptoms and amount of lactose ingested .
As regards, the symptoms questionnaire of 200 patients after ingestion of milk and dairy products, it showed that the mean and SD score of flatulence was 5.69±0.24, abdominal cramping was 3.29±0.16 while diarrhea was 0.84±0.09 and vomiting was 0.30±0.05.
These results agree with the Casellas et al.  study which reported that vomiting was the lowest scored item and flatulence was the highest scored in home-perceived symptoms questionnaire.
It is generally considered difficult to predict lactose malabsorption from symptoms, as when individuals think that they are intolerant to lactose, they tend to avoid dairy products. However, when lactose maldigestion is specifically screened by functional tests such as hydrogen breath test or measuring intestinal lactase, evident discordances arise between objective determinations of lactase activity and symptoms of intolerance .
From the previous 200 patients, 40 adult patients with nonalarming GI tract symptoms underwent upper endoscopy. Their mean age was 35.15±12.14 years, 70.0% were women and 30.0% were men. Most of the studied patients were obese as the mean of their BMI was 29.06±5.87. There was no statistically significant difference as regards, age, sex, BMI, and smoking between the two groups.
From these results, we noticed that most of the patients were adults with their mean age being 35.15±12.14 years. This may be due to the change of lactase activity during development. Lactose intolerance usually begins in childhood, but it is most prevalent in adulthood because the lactase enzyme progressively decreases over the lifespan .
Our study showed that 26 (65%) patients had mild hypolactasia (group I) (values of lactase level in duodenal biopsies 10–30 U/g) compared with (group II) 14 (35%) patients who had normal levels of enzyme (>30 U/g) and no patients were with severe hypolactasia.
These results were compatible with the global incidences which estimated that 70–75% of the world’s population is lactose-deficient ,. Moreover, our results agreed with Mohamed et al. , who reported that 86.67% of adult Egyptian studied patients were diagnosed with lactase deficiency.
Our study showed no statistically significant difference as regards macroscopic or histopathological findings of upper endoscopy between both groups.
This study showed statistically significant difference concerning abdominal cramping and flatulence between both groups with a P value of 0.010 and 0.014, respectively. These results are explained by the fact that lactose fermentation takes place by means of microorganisms in the intestinal gut flora and an osmotic effect is produced by lactose molecules in the GI tract .
Mohamed et al.  reported that patients complaining of abdominal pain were 65.3% and bloating were 89.3%, which is compatible with our results.
Rangel et al.  and Bayless et al.  explained that the abdominal pain may be crampy and often is located in the periumbilical region or in the lower quadrant. Also, Wortmann et al.  reported that abdominal bloating scores were higher in adult-type hypolactasia patients compared with the lactase-persistent patients (P=0.014).
| Conclusion|| |
Our study demonstrates that adult patients with lactose intolerance mainly complain of abdominal cramps and flatulence more than other GI tract symptoms. The study also determined the effectiveness of biochemical assay of lactase enzyme in endoscopic duodenal biopsies in the diagnosis of adult-type hypolactasia; however, the invasiveness of its clinical application limits its use as the first-line investigation to diagnose lactose intolerance.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Misselwitz B, Pohl D, Frühauf H, Fried M, Vavricka SR, Fox M et al.
Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment. United Eur Gastroenterol J
Schirru E, Corona V, Usai-Satta P, Scarpa M. Decline of lactase activity and c/t-13910 variant in Sardinian childhood. J Pediatr Gastroenterol Nutr
Ingram C, Mulcare C, Itan Y, Thomas M, Swallow D. Lactose digestion and the evolutionary genetics of lactase persistence. Hum Genet
Fassio F, Facioni MS, Guagnini F. Lactose maldigestion, malabsorption, and intolerance: a comprehensive review with a focus on current management and future perspectives. Nutrients
Mattar R, De Campos Mazo D, Carrilho F. Lactose intolerance: diagnosis, genetic, and clinical factors. Clin Exp Gastroenterol
Montalto M, Curigliano V, Santoro L, Vastola M, Cammarota G, Manna R et al.
Management and treatment of lactose malabsorption. World J Gastroenterol
Perets T, Shporn E, Aizic S, Kelner E, Levy S, Bareli Y, Dickman R. A diagnostic approach to patients with suspected lactose malabsorption. Dig Dis Sci
Vesa TH, Marteau P, Korpela R. Lactose intolerance. J Am Coll Nutr
2017; 19 (2 Suppl):165S–175S.
Suchy FJ, Brannon PM, Carpenter TO, Fernandes JR, Gilsanz V, Gould JB et al.
National Institutes of Health Consensus Development Conference: lactose intolerance and health. Ann Intern Med
Casellas F, Aparici A, Casaus M, Rodríguez P, Malagelada JR. Subjective perception of lactose intolerance does not always indicate lactose malabsorption. Clin Gastroenterol Hepatol
Corgneau M, Scher J, Ritie-Pertusa L, LE DTL, Petit J, Nikolova Y, Banon S, Gaiani C. Recent advances on lactose intolerance: tolerance thresholds and currently available answers. Crit Rev Food Sci Nutr
Costanzo D, Berni R. Lactose intolerance: common misunderstandings. Ann Nutr Metab
2019; 73(Suppl 4):30–37.
Mohamed MK, Abd ElHafez H, Sabry D. Prevalence of lactase deficiency in adult Egyptian patients with non-alarming gastrointestinal complaints [MSC thesis]
. Cairo, Egypt: Faculty of Medicine, Cairo University; 2018.
Rangel A, Sales D, Galvao J, Andrade J. Lactose intolerance and cow’s milk protein allergy. Food Sci Technol
Bayless TM, Brown E, Paige DM. Lactase non-persistence and lactose intolerance. Curr Gastroenterol Rep
Wortmann AC, Simon D, Mazzoleni LE, Sander GB, Francesconi CFM, Nabinger DD et al.
The association between adult-type hypolactasia and symptoms of functional dyspepsia. Genet Mol Biol
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]