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Self-perceived lactose intolerance and lactose breath test in elderly
European Geriatric Medicine 4 (2013) 372–375
Available online at
www.sciencedirect.com
Research paper
Self-perceived lactose intolerance and lactose breath test in elderly F. Casellas *, A. Aparici, M. Casaus, P. Rodrı´guez Digestive System Research Unit, Hospital Universitari Vall dHebron, Centro de Investigacio´n Biome´dica en Red de Enfermedades Hepa´ticas y Digestivas (Ciberehd), Pso. Vall d’Hebron 119, Barcelona 08035, Spain
A R T I C L E I N F O
A B S T R A C T
Article history: Received 7 April 2013 Accepted 9 July 2013 Available online 2 August 2013
Background: Lactose maldigestion is quite common at all ages. Lactose maldigestion is also common in the elderly but information relative to their symptoms is scarce. Purpose To determine whether in the elderly self-reported lactose intolerance in the normal home setting is comparable to symptoms provoked by a controlled lactose challenge. Design Observational, prospective and transverse study performed in patients referred for a lactose H2 breath test. Material and methods: Patients first completed a validated questionnaire inquiring about symptoms associated with usual consumption of dairy products at home (‘‘home symptoms’’). After a 50-g lactose breath test, symptoms score was also obtained. Patients were grouped as absorbers versus malabsorbers (according to the lactose test result) and younger or older than 65 years old. Results: Six hundred and one patients have been included (89 older than 65 years old and 512 younger than 65 years). Prevalence of lactose maldigestion was the same in both age groups (50% vs 51%). In lactose maldigesters, orocecal transit time and hydrogen excretion capacity after lactose load were independent of age. Oral lactose load induces symptoms in lactose maldigesters. Lactose-induced intolerance symptoms were less intense in elderly than in younger adults (symptoms score of 8 vs 19, P < 0.001). Home symptoms were not related to lactose digestion capacity. Conclusions: In the elderly, lactose maldigestion is associated with increased excretion of hydrogen after oral 50 g lactose load but symptoms are less marked than in younger adults. Self-reported intolerance symptoms at home are not clearly related to lactose maldigestion in elderly. ß 2013 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.
Keywords: Lactose intolerance Lactose maldigestion Hydrogen breath test Lactase activity Elderly
Abbreviation: HBT, hydrogen breath test
1. Key points What is current knowledge? Self-reported lactose intolerance is a very common health problem. True lactose malabsorption requires confirmation with appropriate tests, such as the hydrogen breath test. Lactose deficiency and symptoms of lactose intolerance are poorly correlated. What is new here? In the elderly, symptoms associated with lactose intolerance in the normal home setting tend to be more intense than those experienced after an oral lactose challenge.
* Corresponding author. Tel./fax: +34 93 489 44 56. E-mail address: [email protected] (F. Casellas).
In lactose maldigesters, oral lactose challenge induces symptoms of intolerance that are less marked in the elderly. In the elderly, the ability to produce hydrogen after an oral lactose load in lactose maldigesters is maintained.
2. Background Adult lactose maldigestion is common, but its relation to chronic symptoms of intolerance is unclear. In proven lactose maldigesters, lactose challenge induces symptoms that are independent of the cause of the lactose deficiency [1]. Symptoms of lactose intolerance are, at least in part, related to the amount of unabsorbed lactose. However, symptoms of lactose maldigestion are not directly correlated with intestinal lactase activity [2,3] or with the magnitude of hydrogen production after a lactose load [4– 6]. Patients’ opinion about lactose intolerance is very relevant because self-perceived lactose intolerance is significantly related to lower calcium intake [7]. The discrepancy between lactose intolerance symptoms and lactase activity may be due to a number of factors which can influence the symptomatic perception of
1878-7649/$ – see front matter ß 2013 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved. http://dx.doi.org/10.1016/j.eurger.2013.07.004
F. Casellas et al. / European Geriatric Medicine 4 (2013) 372–375
lactose intolerance, such as lactose load, amount of lactose unabsorbed, type of administration, consumption of lactose during a meal, gastric emptying, small bowel transit, colonic water absorption capacity, effect of colonic bacterial fermentation, or visceral sensitivity [8–10]. However, other subjective variables such as a potential nocebo effect of the lactose test [11] or a tendency towards somatisation [12] cannot be excluded. Thus a test, such as the hydrogen breath test, to confirm that intolerance symptoms are the expression of a true lactose maldigestion is needed at all ages. Lactose maldigestion in the elderly has not been as extensively studied as in other groups of age. It has been reported that in healthy elderly patients there is an apparent increase in the prevalence of lactose maldigestion [13–17]. The exact mechanisms of the lactose maldigestion in the elderly are not completely known, and both mucosal and non-mucosal factors have been proposed, such as an increased presence of small intestinal bacterial overgrowth [18]. Also, as described in adults [19], in the elderly it has also been suggested that perception of lactose intolerance is not always related to lactose malabsorption defined by the results of the hydrogen breath test [17]. Thus, in elderly patients it is also important to confirm in patients with perception of lactose intolerance a true lactose malabsorption with the appropriate tests, such as the hydrogen breath test. The aim of the present study was to evaluate self-reported lactose intolerance symptoms, as perceived in the usual home conditions, and afterwards a lactose challenge in the elderly as compared with younger adults. To this purpose, symptoms believed to be caused by lactose intolerance were evaluated in a group of elderly patients who filled out a validated questionnaire about symptoms perceived under usual conditions at home and after a large oral load of 50 g of lactose.
373
samples were collected in hermetic bags fitted with a three-way valve (GaSampler, Quintron Instruments, Milwaukee, Wisconsin). During the test, patients were instructed to remain seated. Eating, smoking and exercising were not allowed during the test. Hydrogen concentration was determined in breath samples by chromatographic analysis (Quintron model 12i Microlyzer) and expressed as maximal increase over baseline concentration in parts per million (ppm). A positive test was defined as an increase in hydrogen above basal levels greater than 25 ppm, criteria with a sensibility of 95% and specificity of 67% [22]. 3.2.2. Symptoms questionnaire A validated self-administered questionnaire for lactose intolerance was used for symptom assessment [20]. The questionnaire includes five items related to symptoms most frequently reported by lactose-intolerant patients (diarrhea, abdominal cramping, vomiting, audible bowel sounds and flatulence). Symptom severity was self-rated by subjects on a 10-cm visual analogue scale ranging from 0 (without symptoms) to 10 (maximum symptoms). The total score on the questionnaire was obtained as the sum of the individual results of the five visual analogue scales (total ranges from 0 to 50). 3.3. Statistical analysis Depending on age, patients were distributed in two groups: elderly ( 65 years) and adults (< 65 years). Variables were described as median and 25–75% quartiles. Differences between medians were calculated with the Wilcoxon signed rank test or the Kruskal-Wallis ANOVA test. Effect size of the questionnaire was calculated in adults and elderly as the Glass’s d, that uses only the standard deviation of the second group (difference between the means, Mhome Mlactose, divided by the standard deviation of the lactose group, which was regarded as a control group) [24].
3. Methods 4. Results 3.1. Design 4.1. Lactose breath test assessment Six hundred and one Caucasian patients (195 men, 406 women) referred to our Digestive System Research Unit for evaluation of suspected lactose maldigestion by a hydrogen breath test with lactose (lactose-HBT) were prospectively studied after providing informed consent. Patients corresponded to 89 elderly (25 men, 64 women) and 512 adults (170 men, 342 women) according to an age greater or equal to 65 or less than 65 respectively. None had taken antibiotics or been prepared for radiologic or endoscopic examinations for at least 2 weeks prior to entering the study. Patients completed a validated questionnaire [20] on lactose intolerance symptoms twice. First, before the lactose-HBT, being asked about symptoms they related to usual consumption of milkbased products at home (‘‘home symptoms’’). Second, at the end of the lactose-HBT, being asked about symptoms they experienced after the oral 50 g lactose load (‘‘lactose symptoms’’). The standard 50 g lactose dose, equivalent to 1 L of milk, was chosen because it discriminates between lactose absorbers and malabsorbers, based on hydrogen production [21,22].
Lactose-HBT was abnormal, delta increase over 25 ppm, in 45 out of the 89 elderly patients (50.5%) and in 264 out of the 512 adults (51.5%). There were no significant statistical differences in lactose malabsorption prevalence in elderly versus adults. In lactose malabsorbers, the increase in hydrogen excretion over basal after the 50-g lactose load was similar in elderly and in adults (109 [49–168] ppm vs 95 [59–138] ppm respectively, P = ns), suggesting that in the elderly the ability to produce hydrogen after oral lactose load in lactose malabsorption is maintained. Also in lactose malabsorbers, the orocecal transit time, defined as the time interval between ingestion of lactose and the first increase in hydrogen above basal levels over 3 ppm sustained for at least three determinations [25,26], was the same in elderly and in adults (60 [30–90] vs 60 [60–90] respectively, P = ns), suggesting that orocecal transit time after lactose load in lactose malabsorbers does not change with age. 4.2. Perception of lactose intolerance
3.2. Procedure 3.2.1. Hydrogen breath test To perform the 50 g lactose-HBT, following a standardized lowcarbohydrate dinner, overnight fast and thorough brushing of the teeth, end-expiratory breath samples were obtained before and at 30-min intervals after the 50 g lactose load at room temperature [23] for the ensuing 3 hours. If a significant increase in hydrogen in breath was absent, sampling was extended to 5 hours. Breath
Results of total score on the home and lactose symptoms questionnaire are shown in Fig. 1. As expected, after lactose load in the lab, symptoms were more marked in patients with abnormal lactose-HBT (P < 0.01 absorbers vs malabsorbers). Interestingly, with the same amount of lactose, elderly malabsorbers refer significantly fewer symptoms than adults (P < 0.01). In the elderly, lactose absorbers do not have symptoms after the lactose challenge, as happens with adults. Interestingly, adult lactose
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correlation between home symptoms and increase in hydrogen production was also observed in adults with normal lactose absorption (r = 0.06, P = n.s.). On the contrary, lactose symptoms experienced during the breath test were significantly correlated with the measured increase in hydrogen production both in the elderly and in adults (Spearman Rank Order Correlation 0.51 and 0.46, respectively, P < 0.01).
5. Discussion
Fig. 1. Results of the symptom questionnaire according to lactose absorption status as established by lactose-HBT. Upper figure represents the results of total score obtained after 50 g lactose challenge and lower figure home symptoms. Results of adults are represented in grey columns and those of the elderly in white columns. Results are expressed as medians and PC25-PC75. Note that home symptoms are highly scored regardless of lactase-status and the elderly describe fewer symptoms than adults. (*P < 0.05, **P < 0.01).
absorbers refer significantly more symptoms than elderly patients, although much less marked than symptoms referred by lactose malabsorbers. These observations suggest that in the elderly, symptoms related to lactose ingestion are less intense than in adults, both for lactose absorbers and malabsorbers. The questionnaire total score was much higher when used for the assessment of symptoms perceived at home than for symptoms experienced after the test lactose load, and this happened both for absorbers and malabsorbers. In this sense, in the elderly, total score of home symptoms was significantly higher than lactose symptoms in patients with normal lactose-HBT (13 [0–19] vs 0 [0–4] respectively, P < 0.01). Also in the elderly, total score of home symptoms was significantly higher than lactose symptoms in patients with positive lactose-HBT (15 [10–22] vs 8 [3–22] respectively, P = 0.01) Thus, although the 50 g lactose challenge elicited symptoms in many patients, self-perception of intolerance was much higher when recalling symptoms perceived previously under ordinary home conditions. The same pattern was observed also in adult lactose absorbers, whose total score was significantly higher in home conditions than after lactose challenge (16 [7–26] vs 5 [1–13] respectively, P < 0.01). However, in adult lactose malabsorbers, home symptoms were not different than symptoms elicited by lactose challenge (21 [10–30] vs 19 [10–30] respectively, P = ns). The effect size of the total score allowed by the questionnaire was calculated to evaluate the magnitude of the difference in the scoring of the home and lactose symptom questionnaires in the elderly as compared to adults. In the elderly, the effect size was 1.13 and 0.47 for lactose absorbers and malabsorbers respectively, which corresponds to a large and medium effect size. In adults, the effect size was 0.98 and 0.08 respectively. The finding that lactose absorbers reported more marked symptoms at home than after the lactose test load suggests that lactose malabsorption is not the only factor playing a role in the symptoms that patients attributed to consumption of dairy products at home. Consistent with the observation in the elderly with normal lactose absorption relative to the inconsistent correlation between home symptoms and lactose malabsorption is the non-significant correlation between total score of home symptoms and increase in hydrogen production (Spearman Rank Order Correlation = 0.12, P = n.s.). The same non-significant
Lactase deficiency in the elderly is a well-known condition. However, the importance that patients attribute to symptoms that they assume are related to lactase deficiency has scarcely been studied. This is an important aspect because the patient’s decision to keep consuming dairy products or avoid their consumption depends basically on the patient’s perception that symptoms are caused by lactose. The patient’s self-perception that symptoms are related to lactose leads to the avoiding of dairy products [27]. To confirm that lactose maldigestion is really the cause of patient’s symptoms, additional functional explorations, such as the hydrogen breath test, are necessary. The discordance between objective determinations of lactase activity and symptoms found in other age groups has not been extensively studied in the elderly. Thus, the purpose of the present study was to determine the efficacy of lactose-HBT and to improve our understanding of the relationship between symptoms and lactose malabsorption in the elderly. Previous experiences have suggested that the results of the hydrogen breath test are not influenced by age in other malabsorptive diseases such as celiac disease [28]. With that premise we hypothesized that lactose-HBT is not influenced by age, and is also useful to detect lactose malabsorption in elderly patients. Results of our study demonstrate that in the group of elderly patients referred for suspicion of lactose malabsorption, the prevalence of positive lactose-HBT is the same as in adults. Also, in lactose malabsorbers, the delta increase in hydrogen excretion over basal and the orocecal transit time is the same in adults and in the elderly. The potential effect of other influencing factors in hydrogen excretion, such as bacterial overgrowth [18], has not been evaluated in the present study. A positive lactoseHBT indicates malabsorption of lactose, independently of its cause, whether genetically mediated or secondary to intestinal diseases [29]. The cause of the positive lactose-HBT in our study was not evaluated, as this was not the purpose of the study. Also because of the design of our study, we cannot determine the frequency of lactose malabsorption in the elderly in our media, but our results promote future studies to determine the true prevalence of lactose malabsorption in elderly patients using the lactose-HBT. Elderly lactose absorbers do not refer significant symptoms of intolerance after 50 g lactose load. However, elderly patients with lactose malabsorption according to the results of the lactose-HBT, develop symptoms when they consume lactose in the lab. The intensity of symptoms elicited by lactose was correlated with the increase in hydrogen excretion in breath, suggesting that the amount of lactose unabsorbed is a key factor in the symptoms of lactose intolerance. However, other factors, such as psychological characteristics, may also play a role in the subjective perception of lactose intolerance after lactose consumption [30]. Interestingly, symptoms reported by elderly patients are less intense than those reported by adults. The present study also aimed to measure the symptoms self-reported by elderly patients when consuming dairy products at home and compare them with the symptoms elicited by a high-dose 50 g lactose challenge. Patients were grouped as lactose absorbers/malabsorbers depending on the
F. Casellas et al. / European Geriatric Medicine 4 (2013) 372–375
result of the lactose-HBT. Our results show that in the elderly, as in adults, self-reported symptoms of lactose intolerance are disproportionately more intense than symptoms elicited by a challenge dose of 50 g of lactose. These results confirm the discrepancy between symptoms our patients attributed to lactose intolerance and symptoms elicited by a large lactose load in the laboratory [4,19]. Why symptoms perceived at home are more intense than after lactose challenge is not completely understood. Perhaps it could be related to the home environment, such as the effect of other nutrients, or, more likely, it is not due to lactose malabsorption but to other causes. This latter explanation is supported by the fact that lactose absorbers, with a normal lactose-HBT, had much higher scores on the symptoms questionnaire at home than after the lactose test. Another hypothetical explanation that cannot be excluded because the design of the study includes the presence of confounding overlooked conditions, such as irritable bowel disease, celiac disease or inflammatory bowel disease. These diseases, among others, are relatively common in the elderly, may cause digestive symptoms resembling those of lactose intolerance and are associated with avoidance of dairy products. Independently of the origin of the gastrointestinal symptoms that patients attribute to lactose, it is very relevant the fact that self-reported milk intolerance is a key factor in the avoidance of milk and is associated with a low daily calcium intake, even lower than the recommended level, both in adults and elderly subjects [31]. Another aspect to be considered is that lactose-HBT is an indirect method that allows quantification, but which can be influenced by other different factors, such as intestinal microbiota. In conclusion, results of the present study suggest that lactoseHBT is a useful tool to identify lactose malabsorption in the elderly population. Another important finding is that lactose malabsorption in elderly subjects is at least as frequent as in other age groups, although lactose intolerance symptoms are less marked in the elderly as compared with adults. Another original contribution is the fact that self-perceived lactose intolerance in usual home conditions is very important and not clearly related to the capacity of lactose digestion. As a consequence, the study of suspected lactose intolerance as a result of the clinical history has to be complemented with an objective test, such as the lactose-HBT. In conclusion, before advising restriction of normal amounts of dairy products in elderly patients because of patient self-perceived lactose intolerance, specific procedures such as the lactose-HBT should be performed to confirm the presence of true lactose malabsorption. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Acknowledgements Ciberehd is funded by the Instituto de Salud Carlos III, Spain. This work was supported in part by grants from the Generalitat de Catalunya (RE: 2001SGR00389) and Centro de Investigacio´n Biome´dica en Red de Enfermedades Hepa´ticas y Digestivas (Ciberehd, Spain). References [1] Melvin BH, The Committee on Nutrition. Lactose intolerance in infants, children and adolescents. Pediatrics 2006;118:1279–86.
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[2] Iqbal TH, Bradley R, Reilly KO, et al. Small intestinal lactase status, frequency distribution of enzyme activity and milk intake in a multi-ethnic population. Clin Nutr 1996;15:297–302. [3] Gupta SK, Chong SKF, Fitzgerald JF. Disaccharidase activities in children: normal values and comparison based on symptoms and histologic changes. J Pediatr Gastroenterol Nutr 1999;28:246–51. [4] Suarez FL, Savaiano DA, Levitt MD. A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance. N Engl J Med 1995;333:1–4. [5] Leis R, Tojo R, Pavo´n P, Douwes A. Prevalence of lactose malabsorption in Galicia. J Pediatr Gastroenterol Nutr 1997;25:296–300. [6] Vernia P, Camillo M, Marinaro V, et al. Lactose malabsorption and the genesis of irritable bowel syndrome symptoms. Gastroenterology 2001;120(Suppl. 1): A264. [7] Nicklas TA, Qu H, Hughes SO, et al. Self-perceived lactose intolerance results in lower intakes of calcium and dairy foods and is associated with hypertension and diabetes in adults. Am J Clin Nutr 2011;94:191–8. [8] Vonk RJ, Priebe MG, Koetse HA, et al. Lactose intolerance: analysis of underlying factors. Eur J Clin Invest 2003;33:70–5. [9] Martini MC, Savaiano DA. Reduced intolerance symptoms from lactose consumed during a meal. Am J Clin Nutr 1988;47:57–60. [10] He T, Priebe MG, Harmsen HJ, Stellaard F, et al. Colonic fermentation may play a role in lactose intolerance in humans. J Nutr 2006;136:58–63. [11] Vernia P, Di Camillo M, Foglietta T, Avallone VE, De Carolis A. Diagnosis of lactose intolerance and the nocebo effect: the role of negative expectations. Dig Liver Dis 2010;42:616–9. [12] Tomba C, Baldassarri A, Coletta M, Cesana BM, Basilisco G. Is the subjective perception of lactose intolerance influenced by the psychological profile? Aliment Pharmacol Ther 2012;36:660–9. [13] Di Stefano M, Veneto G, Malservisi S, Strocchi A, Corazza GR. Lactose malabsorption in the elderly. Scand J Gastroenterol 2001;36:1274–8. [14] Feibusch JH, Holt PR. Impaired absorptive capacity for carbohydrate in the ageing human. Dig Dis Sci 1982;27:1095–100. [15] Goulding A, Taylor RW, Keil D, et al. Lactose malabsorption and rate of bone loss in older women. Age Ageing 1999;28:175–80. [16] Rao DM, Bello H, Warren AP, Brown GE. Prevalence of lactose maldigestion. Influence and interaction of age, race and sex. Dig Dis Sci 1994;39:1519–24. [17] Rorick MH, Scrimshaw NS. Comparative tolerance of elderly from differing ethnic backgrounds to lactose-containing and lactose-free dairy drinks: a double-blind study. J Gerontology 1979;34:191–6. [18] Almeida JA, Kim R, Stoita A, Mciver CJ, Kurtovic J, Riordan SM. Lactose malabsorption in the elderly: role of small intestinal bacterial overgrowth. Scand J Gastroenterol 2008;43:146–54. [19] Casellas F, Aparici A, Casaus M, Rodrı´guez P, Malagelada JR. Subjective perception of lactose intolerance does not always indicate lactose malabsorption. Clin Gastroenterol Hepatol 2010;8:581–6. [20] Casellas F, Varela E, Aparici A, Casaus M, Rodrı´guez P. Development, validation and applicability of a symptoms questionnaire for lactose malabsorption screening. Dig Dis Sci 2009;54:1059–65. [21] Eisenmann A, Amann A, Said M, Datta B, Ledochowski M. Implementation and interpretation of hydrogen breath tests. J Breath Res 2008;2:1–9. [22] Casellas F, Malagelada JR. Applicability of short hydrogen breath test for screening of lactose malabsorption. Dig Dis Sci 2003;48:1333–8. [23] Peuhkuri K, Vapaatalo H, Nevala R, et al. Temperature of a test solution influences abdominal symptoms in lactose tolerance tests. Scand J Clin Lab Invest 2000;60:75–80. [24] Ledesma RD, Macbeth G, Cortada N. Computing effect size measures with ViSta. The visual statistics system. Tutorials Quant Methods Psychol 2009;5:25–34. [25] Fort JM, Azpiroz F, Casellas F, Andreu J, Malagelada JR. Bowel habit after cholecystectomy: physiological changes and clinical implications. Gastroenterology 1996;111:617–22. [26] Casellas F, Aparici A, Casaus M, Rodrı´guez P, Malagelada JR. Impact of orocecal transit time on patient’s perception of lactose intolerance. Rev Esp Enferm Dig 2013;105:13–8. [27] Qiao R, Huang C, Du H, Zeng G, Li L, Ye S. Milk consumption and lactose intolerance in adults. Biomed Environ Sci 2011;24:512–7. [28] Casellas F, Chicharro L, Malagelada JR. Potential usefulness of hydrogen breath test with D-xylose in clinical management of intestinal malabsorption. Dig Dis Sci 1993;38:321–7. [29] Krawczyk M, Wolska M, Schwartz S, et al. Concordance of genetic and breath tests for lactose intolerance in a tertiary referral centre. J Gastrointestin Liver Dis 2008;17:135–9. [30] Tomba C, Baldassarri A, Coletta M, et al. Is the subjective perception of lactose intolerance influenced by the psychological profile? Aliment Pharmacol Ther 2012;36:660–9. [31] Carroccio A, Moltalto G, Cavera G, Notarbatolo A, the Lactase Deficiency Study Group. Lactose intolerance and self-reported milk intolerance: relationship with lactose maldigestion and nutrient intake. J Am Coll Nutr 1998;17: 631–6.
Available online at
www.sciencedirect.com
Research paper
Self-perceived lactose intolerance and lactose breath test in elderly F. Casellas *, A. Aparici, M. Casaus, P. Rodrı´guez Digestive System Research Unit, Hospital Universitari Vall dHebron, Centro de Investigacio´n Biome´dica en Red de Enfermedades Hepa´ticas y Digestivas (Ciberehd), Pso. Vall d’Hebron 119, Barcelona 08035, Spain
A R T I C L E I N F O
A B S T R A C T
Article history: Received 7 April 2013 Accepted 9 July 2013 Available online 2 August 2013
Background: Lactose maldigestion is quite common at all ages. Lactose maldigestion is also common in the elderly but information relative to their symptoms is scarce. Purpose To determine whether in the elderly self-reported lactose intolerance in the normal home setting is comparable to symptoms provoked by a controlled lactose challenge. Design Observational, prospective and transverse study performed in patients referred for a lactose H2 breath test. Material and methods: Patients first completed a validated questionnaire inquiring about symptoms associated with usual consumption of dairy products at home (‘‘home symptoms’’). After a 50-g lactose breath test, symptoms score was also obtained. Patients were grouped as absorbers versus malabsorbers (according to the lactose test result) and younger or older than 65 years old. Results: Six hundred and one patients have been included (89 older than 65 years old and 512 younger than 65 years). Prevalence of lactose maldigestion was the same in both age groups (50% vs 51%). In lactose maldigesters, orocecal transit time and hydrogen excretion capacity after lactose load were independent of age. Oral lactose load induces symptoms in lactose maldigesters. Lactose-induced intolerance symptoms were less intense in elderly than in younger adults (symptoms score of 8 vs 19, P < 0.001). Home symptoms were not related to lactose digestion capacity. Conclusions: In the elderly, lactose maldigestion is associated with increased excretion of hydrogen after oral 50 g lactose load but symptoms are less marked than in younger adults. Self-reported intolerance symptoms at home are not clearly related to lactose maldigestion in elderly. ß 2013 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.
Keywords: Lactose intolerance Lactose maldigestion Hydrogen breath test Lactase activity Elderly
Abbreviation: HBT, hydrogen breath test
1. Key points What is current knowledge? Self-reported lactose intolerance is a very common health problem. True lactose malabsorption requires confirmation with appropriate tests, such as the hydrogen breath test. Lactose deficiency and symptoms of lactose intolerance are poorly correlated. What is new here? In the elderly, symptoms associated with lactose intolerance in the normal home setting tend to be more intense than those experienced after an oral lactose challenge.
* Corresponding author. Tel./fax: +34 93 489 44 56. E-mail address: [email protected] (F. Casellas).
In lactose maldigesters, oral lactose challenge induces symptoms of intolerance that are less marked in the elderly. In the elderly, the ability to produce hydrogen after an oral lactose load in lactose maldigesters is maintained.
2. Background Adult lactose maldigestion is common, but its relation to chronic symptoms of intolerance is unclear. In proven lactose maldigesters, lactose challenge induces symptoms that are independent of the cause of the lactose deficiency [1]. Symptoms of lactose intolerance are, at least in part, related to the amount of unabsorbed lactose. However, symptoms of lactose maldigestion are not directly correlated with intestinal lactase activity [2,3] or with the magnitude of hydrogen production after a lactose load [4– 6]. Patients’ opinion about lactose intolerance is very relevant because self-perceived lactose intolerance is significantly related to lower calcium intake [7]. The discrepancy between lactose intolerance symptoms and lactase activity may be due to a number of factors which can influence the symptomatic perception of
1878-7649/$ – see front matter ß 2013 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved. http://dx.doi.org/10.1016/j.eurger.2013.07.004
F. Casellas et al. / European Geriatric Medicine 4 (2013) 372–375
lactose intolerance, such as lactose load, amount of lactose unabsorbed, type of administration, consumption of lactose during a meal, gastric emptying, small bowel transit, colonic water absorption capacity, effect of colonic bacterial fermentation, or visceral sensitivity [8–10]. However, other subjective variables such as a potential nocebo effect of the lactose test [11] or a tendency towards somatisation [12] cannot be excluded. Thus a test, such as the hydrogen breath test, to confirm that intolerance symptoms are the expression of a true lactose maldigestion is needed at all ages. Lactose maldigestion in the elderly has not been as extensively studied as in other groups of age. It has been reported that in healthy elderly patients there is an apparent increase in the prevalence of lactose maldigestion [13–17]. The exact mechanisms of the lactose maldigestion in the elderly are not completely known, and both mucosal and non-mucosal factors have been proposed, such as an increased presence of small intestinal bacterial overgrowth [18]. Also, as described in adults [19], in the elderly it has also been suggested that perception of lactose intolerance is not always related to lactose malabsorption defined by the results of the hydrogen breath test [17]. Thus, in elderly patients it is also important to confirm in patients with perception of lactose intolerance a true lactose malabsorption with the appropriate tests, such as the hydrogen breath test. The aim of the present study was to evaluate self-reported lactose intolerance symptoms, as perceived in the usual home conditions, and afterwards a lactose challenge in the elderly as compared with younger adults. To this purpose, symptoms believed to be caused by lactose intolerance were evaluated in a group of elderly patients who filled out a validated questionnaire about symptoms perceived under usual conditions at home and after a large oral load of 50 g of lactose.
373
samples were collected in hermetic bags fitted with a three-way valve (GaSampler, Quintron Instruments, Milwaukee, Wisconsin). During the test, patients were instructed to remain seated. Eating, smoking and exercising were not allowed during the test. Hydrogen concentration was determined in breath samples by chromatographic analysis (Quintron model 12i Microlyzer) and expressed as maximal increase over baseline concentration in parts per million (ppm). A positive test was defined as an increase in hydrogen above basal levels greater than 25 ppm, criteria with a sensibility of 95% and specificity of 67% [22]. 3.2.2. Symptoms questionnaire A validated self-administered questionnaire for lactose intolerance was used for symptom assessment [20]. The questionnaire includes five items related to symptoms most frequently reported by lactose-intolerant patients (diarrhea, abdominal cramping, vomiting, audible bowel sounds and flatulence). Symptom severity was self-rated by subjects on a 10-cm visual analogue scale ranging from 0 (without symptoms) to 10 (maximum symptoms). The total score on the questionnaire was obtained as the sum of the individual results of the five visual analogue scales (total ranges from 0 to 50). 3.3. Statistical analysis Depending on age, patients were distributed in two groups: elderly ( 65 years) and adults (< 65 years). Variables were described as median and 25–75% quartiles. Differences between medians were calculated with the Wilcoxon signed rank test or the Kruskal-Wallis ANOVA test. Effect size of the questionnaire was calculated in adults and elderly as the Glass’s d, that uses only the standard deviation of the second group (difference between the means, Mhome Mlactose, divided by the standard deviation of the lactose group, which was regarded as a control group) [24].
3. Methods 4. Results 3.1. Design 4.1. Lactose breath test assessment Six hundred and one Caucasian patients (195 men, 406 women) referred to our Digestive System Research Unit for evaluation of suspected lactose maldigestion by a hydrogen breath test with lactose (lactose-HBT) were prospectively studied after providing informed consent. Patients corresponded to 89 elderly (25 men, 64 women) and 512 adults (170 men, 342 women) according to an age greater or equal to 65 or less than 65 respectively. None had taken antibiotics or been prepared for radiologic or endoscopic examinations for at least 2 weeks prior to entering the study. Patients completed a validated questionnaire [20] on lactose intolerance symptoms twice. First, before the lactose-HBT, being asked about symptoms they related to usual consumption of milkbased products at home (‘‘home symptoms’’). Second, at the end of the lactose-HBT, being asked about symptoms they experienced after the oral 50 g lactose load (‘‘lactose symptoms’’). The standard 50 g lactose dose, equivalent to 1 L of milk, was chosen because it discriminates between lactose absorbers and malabsorbers, based on hydrogen production [21,22].
Lactose-HBT was abnormal, delta increase over 25 ppm, in 45 out of the 89 elderly patients (50.5%) and in 264 out of the 512 adults (51.5%). There were no significant statistical differences in lactose malabsorption prevalence in elderly versus adults. In lactose malabsorbers, the increase in hydrogen excretion over basal after the 50-g lactose load was similar in elderly and in adults (109 [49–168] ppm vs 95 [59–138] ppm respectively, P = ns), suggesting that in the elderly the ability to produce hydrogen after oral lactose load in lactose malabsorption is maintained. Also in lactose malabsorbers, the orocecal transit time, defined as the time interval between ingestion of lactose and the first increase in hydrogen above basal levels over 3 ppm sustained for at least three determinations [25,26], was the same in elderly and in adults (60 [30–90] vs 60 [60–90] respectively, P = ns), suggesting that orocecal transit time after lactose load in lactose malabsorbers does not change with age. 4.2. Perception of lactose intolerance
3.2. Procedure 3.2.1. Hydrogen breath test To perform the 50 g lactose-HBT, following a standardized lowcarbohydrate dinner, overnight fast and thorough brushing of the teeth, end-expiratory breath samples were obtained before and at 30-min intervals after the 50 g lactose load at room temperature [23] for the ensuing 3 hours. If a significant increase in hydrogen in breath was absent, sampling was extended to 5 hours. Breath
Results of total score on the home and lactose symptoms questionnaire are shown in Fig. 1. As expected, after lactose load in the lab, symptoms were more marked in patients with abnormal lactose-HBT (P < 0.01 absorbers vs malabsorbers). Interestingly, with the same amount of lactose, elderly malabsorbers refer significantly fewer symptoms than adults (P < 0.01). In the elderly, lactose absorbers do not have symptoms after the lactose challenge, as happens with adults. Interestingly, adult lactose
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correlation between home symptoms and increase in hydrogen production was also observed in adults with normal lactose absorption (r = 0.06, P = n.s.). On the contrary, lactose symptoms experienced during the breath test were significantly correlated with the measured increase in hydrogen production both in the elderly and in adults (Spearman Rank Order Correlation 0.51 and 0.46, respectively, P < 0.01).
5. Discussion
Fig. 1. Results of the symptom questionnaire according to lactose absorption status as established by lactose-HBT. Upper figure represents the results of total score obtained after 50 g lactose challenge and lower figure home symptoms. Results of adults are represented in grey columns and those of the elderly in white columns. Results are expressed as medians and PC25-PC75. Note that home symptoms are highly scored regardless of lactase-status and the elderly describe fewer symptoms than adults. (*P < 0.05, **P < 0.01).
absorbers refer significantly more symptoms than elderly patients, although much less marked than symptoms referred by lactose malabsorbers. These observations suggest that in the elderly, symptoms related to lactose ingestion are less intense than in adults, both for lactose absorbers and malabsorbers. The questionnaire total score was much higher when used for the assessment of symptoms perceived at home than for symptoms experienced after the test lactose load, and this happened both for absorbers and malabsorbers. In this sense, in the elderly, total score of home symptoms was significantly higher than lactose symptoms in patients with normal lactose-HBT (13 [0–19] vs 0 [0–4] respectively, P < 0.01). Also in the elderly, total score of home symptoms was significantly higher than lactose symptoms in patients with positive lactose-HBT (15 [10–22] vs 8 [3–22] respectively, P = 0.01) Thus, although the 50 g lactose challenge elicited symptoms in many patients, self-perception of intolerance was much higher when recalling symptoms perceived previously under ordinary home conditions. The same pattern was observed also in adult lactose absorbers, whose total score was significantly higher in home conditions than after lactose challenge (16 [7–26] vs 5 [1–13] respectively, P < 0.01). However, in adult lactose malabsorbers, home symptoms were not different than symptoms elicited by lactose challenge (21 [10–30] vs 19 [10–30] respectively, P = ns). The effect size of the total score allowed by the questionnaire was calculated to evaluate the magnitude of the difference in the scoring of the home and lactose symptom questionnaires in the elderly as compared to adults. In the elderly, the effect size was 1.13 and 0.47 for lactose absorbers and malabsorbers respectively, which corresponds to a large and medium effect size. In adults, the effect size was 0.98 and 0.08 respectively. The finding that lactose absorbers reported more marked symptoms at home than after the lactose test load suggests that lactose malabsorption is not the only factor playing a role in the symptoms that patients attributed to consumption of dairy products at home. Consistent with the observation in the elderly with normal lactose absorption relative to the inconsistent correlation between home symptoms and lactose malabsorption is the non-significant correlation between total score of home symptoms and increase in hydrogen production (Spearman Rank Order Correlation = 0.12, P = n.s.). The same non-significant
Lactase deficiency in the elderly is a well-known condition. However, the importance that patients attribute to symptoms that they assume are related to lactase deficiency has scarcely been studied. This is an important aspect because the patient’s decision to keep consuming dairy products or avoid their consumption depends basically on the patient’s perception that symptoms are caused by lactose. The patient’s self-perception that symptoms are related to lactose leads to the avoiding of dairy products [27]. To confirm that lactose maldigestion is really the cause of patient’s symptoms, additional functional explorations, such as the hydrogen breath test, are necessary. The discordance between objective determinations of lactase activity and symptoms found in other age groups has not been extensively studied in the elderly. Thus, the purpose of the present study was to determine the efficacy of lactose-HBT and to improve our understanding of the relationship between symptoms and lactose malabsorption in the elderly. Previous experiences have suggested that the results of the hydrogen breath test are not influenced by age in other malabsorptive diseases such as celiac disease [28]. With that premise we hypothesized that lactose-HBT is not influenced by age, and is also useful to detect lactose malabsorption in elderly patients. Results of our study demonstrate that in the group of elderly patients referred for suspicion of lactose malabsorption, the prevalence of positive lactose-HBT is the same as in adults. Also, in lactose malabsorbers, the delta increase in hydrogen excretion over basal and the orocecal transit time is the same in adults and in the elderly. The potential effect of other influencing factors in hydrogen excretion, such as bacterial overgrowth [18], has not been evaluated in the present study. A positive lactoseHBT indicates malabsorption of lactose, independently of its cause, whether genetically mediated or secondary to intestinal diseases [29]. The cause of the positive lactose-HBT in our study was not evaluated, as this was not the purpose of the study. Also because of the design of our study, we cannot determine the frequency of lactose malabsorption in the elderly in our media, but our results promote future studies to determine the true prevalence of lactose malabsorption in elderly patients using the lactose-HBT. Elderly lactose absorbers do not refer significant symptoms of intolerance after 50 g lactose load. However, elderly patients with lactose malabsorption according to the results of the lactose-HBT, develop symptoms when they consume lactose in the lab. The intensity of symptoms elicited by lactose was correlated with the increase in hydrogen excretion in breath, suggesting that the amount of lactose unabsorbed is a key factor in the symptoms of lactose intolerance. However, other factors, such as psychological characteristics, may also play a role in the subjective perception of lactose intolerance after lactose consumption [30]. Interestingly, symptoms reported by elderly patients are less intense than those reported by adults. The present study also aimed to measure the symptoms self-reported by elderly patients when consuming dairy products at home and compare them with the symptoms elicited by a high-dose 50 g lactose challenge. Patients were grouped as lactose absorbers/malabsorbers depending on the
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result of the lactose-HBT. Our results show that in the elderly, as in adults, self-reported symptoms of lactose intolerance are disproportionately more intense than symptoms elicited by a challenge dose of 50 g of lactose. These results confirm the discrepancy between symptoms our patients attributed to lactose intolerance and symptoms elicited by a large lactose load in the laboratory [4,19]. Why symptoms perceived at home are more intense than after lactose challenge is not completely understood. Perhaps it could be related to the home environment, such as the effect of other nutrients, or, more likely, it is not due to lactose malabsorption but to other causes. This latter explanation is supported by the fact that lactose absorbers, with a normal lactose-HBT, had much higher scores on the symptoms questionnaire at home than after the lactose test. Another hypothetical explanation that cannot be excluded because the design of the study includes the presence of confounding overlooked conditions, such as irritable bowel disease, celiac disease or inflammatory bowel disease. These diseases, among others, are relatively common in the elderly, may cause digestive symptoms resembling those of lactose intolerance and are associated with avoidance of dairy products. Independently of the origin of the gastrointestinal symptoms that patients attribute to lactose, it is very relevant the fact that self-reported milk intolerance is a key factor in the avoidance of milk and is associated with a low daily calcium intake, even lower than the recommended level, both in adults and elderly subjects [31]. Another aspect to be considered is that lactose-HBT is an indirect method that allows quantification, but which can be influenced by other different factors, such as intestinal microbiota. In conclusion, results of the present study suggest that lactoseHBT is a useful tool to identify lactose malabsorption in the elderly population. Another important finding is that lactose malabsorption in elderly subjects is at least as frequent as in other age groups, although lactose intolerance symptoms are less marked in the elderly as compared with adults. Another original contribution is the fact that self-perceived lactose intolerance in usual home conditions is very important and not clearly related to the capacity of lactose digestion. As a consequence, the study of suspected lactose intolerance as a result of the clinical history has to be complemented with an objective test, such as the lactose-HBT. In conclusion, before advising restriction of normal amounts of dairy products in elderly patients because of patient self-perceived lactose intolerance, specific procedures such as the lactose-HBT should be performed to confirm the presence of true lactose malabsorption. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Acknowledgements Ciberehd is funded by the Instituto de Salud Carlos III, Spain. This work was supported in part by grants from the Generalitat de Catalunya (RE: 2001SGR00389) and Centro de Investigacio´n Biome´dica en Red de Enfermedades Hepa´ticas y Digestivas (Ciberehd, Spain). References [1] Melvin BH, The Committee on Nutrition. Lactose intolerance in infants, children and adolescents. Pediatrics 2006;118:1279–86.
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