Clinical and Laboratory Pearl

Lactose Intolerance and Self-Reported Milk Intolerance: Relationship with Lactose Maldigestion and Nutrient Intake A. Carroccio, MD, G. Montalto, G. Cavera, MD, A. Notarbatolo, MD, and the Lactase Deficiency Study Group Istituto di Medicina Interna, Universita` di Palermo, ITALY Key words: lactose maldigestion, lactose intolerance, milk consumption, calcium intake, H2 breath test, dietary investigation Background: The relationship between lactose-maldigestion, self-reported milk intolerance and gastrointestinal symptoms has not been clearly defined. Objectives: To evaluate: a) the prevalence of lactose maldigestion and lactose intolerance in a sample of the general population taken from a rural center; b) the frequency of self-reported milk-intolerance and its correlation with lactose-maldigestion; c) the influence of lactose maldigestion, lactose intolerance and self-reported milk intolerance on dietary habits and consumption of total calories, protein, and calcium. Subjects: We studied a randomized sample of the general population in a small center in Sicily. 323 subjects (150 males, 173 females), age range 5 to 85 years (median 44) were included and underwent H2-breath test after 25 g lactose load. The preliminary dietary investigation spanned 7 consecutive days using a printed dietary form and was under the daily control of a team of dietitians. Methods: The dietary investigation was completed in the first part of the study and the results were analyzed for nutrient composition by a computerized database. The subjects were then divided into self-reported milk-intolerants and self-reported milk-tolerants and they underwent H2 breath testing; subjects with H2 concentration .20 ppm over the baseline concentration were considered maldigesters and those with one or more symptoms were classified as intolerants. Results: 104/323 subjects (32.2%) were lactose maldigesters but tolerants, while 13/323 (4%) were lactose maldigesters and intolerants. In each age-class group (pediatric, adult, and elderly subjects) only the lactose maldigester and intolerant subjects showed differences in nutrient intake with a significantly lower daily consumption of milk and a lower calcium intake. 49/323 subjects were self-reported milk-intolerants; of these, 26 (53%) were lactose maldigesters but tolerants, 18 (37%) were lactose digesters and tolerants and only 5 (10%) were lactose maldigesters and intolerants. In the whole group of self-reported milk-intolerants, dietary milk consumption was significantly reduced and calcium intake was lower than in all the other subjects studied (320 mg/day vs. 585 mg/day, p,0.05). Conclusions: In studies of the general population, the frequency of lactose intolerance is much lower than that of lactose maldigestion. Gastrointestinal symptoms after lactose load in self-reported milk-intolerants are found in only a very low number of these subjects. Furthermore, in these subjects we observed an unnecessary reduction in milk consumption and an insufficient dietary calcium intake.

INTRODUCTION

border [1– 4]. The incidence of lactose maldigestion ranges from 11% to 60% in Europe [5] and this condition can cause gastrointestinal symptoms such as abdominal pain, bloating, flatulence, diarrhea [6 – 8]. However, the correlation between

Adult-type hypolactasia is determined by a genetically programmed reduction in lactase activity at the intestinal brush

Co-Authors of this paper as components of the Lactase Deficiency Study Group are: Giovanni Anastasi, Giulio Bonfissuto, Piero Campagna, Giovanni Costanza, Marcella Fulco, Salvatore Gallo, Lidia Giannitrapani, Salvatore Ippolito, Carmela Magliarisi, Laura Pagano, Maurizio Soresi, Filippo Vasile Testai. Address reprint requests to: Antonio Carroccio MD, via A. Coffaro 25, 90124, Palermo, Italy.

Journal of the American College of Nutrition, Vol. 17, No. 6, 631–636 (1998) Published by the American College of Nutrition 631

Lactose Intolerance and Maldigestion lactose malabsorption and clinical symptoms is unclear: many malabsorbers are in fact able to tolerate a certain quantity of milk without presenting symptoms [9,10], while many cases of self-reported milk-intolerance remain asymptomatic after lactose oral load [11,12]. The results of these latter studies suggest that a part of the population chooses not to consume milk and its derivatives without reason. However, there are no studies to our knowledge which have evaluated the frequency of unnecessary self-limitation of milk and its derivatives in the general population or the influence of self-reported milk-intolerance on dietary intake of the main nutrients. The present study reports the results of a dietary investigation and a clinical evaluation of lactose digestion, focusing on self-reported milk-intolerance, in a wide, randomized sample of the general population in a small rural center.

PATIENTS AND METHODS The study was performed in the town of Ventimiglia di Sicilia, in Sicily. It is a small rural center whose 1400 inhabitants (642 males, 764 females) are mainly occupied in agriculture. On the basis of demographic population data, already used in previous researchs [13–15], we took a randomized sample representative of the general population. In brief, we decided to study a sample 25% of the whole population. From demographic data, we knew that the age distribution of the inhabitants was approximately the following: 20% range 5 to 16 years, 45% 17 to 64 years and 35% over 65. Thus, we randomly chose 350 names from the complete list of the population, respecting the proportion according to the age distribution, so that the study sample reflected the age distribution of the whole population. In collaboration with the local health services, we thus enrolled 350 subjects to participate in the study. The research protocol was completed in 323 subjects (150 males, 173 females), age range 5 to 85 years (median 44); we excluded 27 subjects for one or more of the following causes: known intestinal disease, episodes of diarrhea, consumption of antibiotics or laxatives during the 3 weeks prior to the investigation. The study was divided into two successive phases. During the first period the subjects received a dietary form containing a printed list of the most common foods. They were carefully trained in the compilation of this form and each subject recorded the daily consumption of each food for 7 days (Monday-Sunday). The less common foods, not appearing on the printed list were also noted, together with their quantities. For the younger children, the food records were compiled by their parents. To reduce variability in collecting dietary data, they were visited daily by a dietitian to check the data reported on the form. Final forms were analyzed by a computerized database and nutrient intakes were calculated using the nutrient composition database of the Italian National Institute for Nutrition [16]. During the second study period the subjects were requested

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to attend the town health care clinic in groups of 10 per day. Before carrying out the breath tests, we recorded an accurate clinical history with particular reference to the presence of gastrointestinal disorders and use of drugs. Furthermore, we asked the subjects whether they thought they suffered from any particular disorders after consuming milk and its derivatives and if they consequently limited consumption. The lactose breath test was performed after an overnight fast of 10 to 12 hours, and 1 g/kg lactose was administered to children weighing ,25 kg and a standard dose of 25 g was given to all the other subjects, suspended in 250 to 300 ml of water (0.30 mol per liter). A baseline alveolar breath sample was taken before ingestion of the acquous lactose. Breath samples were collected at 30-minute intervals from the time of ingestion over a period of 3 hours and the hydrogen concentration in each breath sample was measured using the 12 Quintron Microlyzer (Quintron Instruments, Milwaukee, WI). Subjects were instructed not to eat or drink anything until the completion of the test. Subjects with an increase in breath hydrogen concentration . 20 ppm over baseline concentration were termed maldigesters, and those with one or more symptoms were classified as intolerants. Subjects whose hydrogen concentration increased ,20 ppm over baseline were termed digesters, and those without symptoms were classified as tolerants. All the subjects undergoing the test were contacted after 24 hours to evaluate the appearance of the following symptoms after the lactose challenge: abdominal pain or cramps, bloating, flatulence and diarrhea (defined as an urgent, watery defecation). The presence of these symptoms was recorded by the subjects (or for the younger children by their parents) and self-rated on a scale of 0 –5 as follows: 05indicated no symptoms, 15trivial symptoms, 25mild symptoms, 35moderate symptoms, 45strong symptoms and 55severe symptoms [17,18]. In the case of subjects who defined themselves as intolerant to milk but had a hydrogen breath test showing a normal lactose absorption capacity (alveolar H2 concentration ,20 ppm), we evaluate the ability of the colonic flora to produce hydrogen through fermentation in response to carbohydrate malabsorption. In fact, these subjects were recalled over the following 8 days and, with the same procedure as the lactose load, 12 g of lactulose (120 ml) was administered and breath H2 excretion was measured. Lactulose is a non-absorbable disaccharide that is fermented by the same enzymatic pathway as lactose. All subjects consented to participate in the study; for children, consent was requested and obtained from their parents.

Statistical Analysis The frequencies were compared using Fisher’s exact test or the chi square test, where appropriate. The Kruskall-Wallis test was used to compare daily intake of milk and its products and the various dietary components in the different patient groups

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Lactose Intolerance and Maldigestion divided on the basis of: a) lactose digestion capacity—H2breath test; and b) self-reported milk intolerance. Finally, we calculated range and median values of all dietary components.

RESULTS The H2-breath test showed that 117/323 (36.2%) of the study subjects were lactose-maldigesters. As was predictable, the frequency of cases of maldigesters increased as subject age increased: in the pediatric age group (range 5 to 16 years) prevalence was 23% (17/72 subjects), in the adults group (age range 17 to 64 years) prevalence was 38% (54/141 subjects) in the group of elderly subjects (age range 65 to 85 years) prevalence was 42% (46/110 subjects). Only 13 of the maldigesters complained of symptoms in the hours following lactose load; of these subjects, two were in the pediatric age group, six in the adult group and five in the elderly group. The severity score of the symptoms in these subjects ranged between 1 and 4. Furthermore, three subjects with H2 breath test within normal limits reported abdominal pains. We therefore identified a total of 104/323 subjects (32.2%) as lactose maldigesters but tolerants, 13/323 subjects (4%) as maldigesters and intolerants, 3/323 subjects (1%) as digesters but intolerants and 203/323 subjects (62.8%) as digesters and tolerants. As expected, mean age of the digesters-tolerants (41.6126.8 years) was significantly lower than that of maldigesters-tolerants (53.6123.8 years) (z52.52, p,0.02, Kruskall-Wallis test) and that of maldigesters-intolerants (52.2119.8 years) (z52.41, p,0.03, Kruskall-Wallis test). No difference in sex distribution was observed between the groups. Table 1 shows data referring to consumption of milk and cheese and intake of nutrients in the study subjects of pediatric age, divided according to the result of the H2-breath test. It can be seen that milk consumption was significantly lower in the patients classified as lactose maldigesters and intolerants. No differences were observed between the three groups in total calories, proteins and calcium intake, although the latter was much lower in the intolerant children. Tables 2 and 3 show the same data in the adult and elderly subjects, respectively. Also in these age groups, milk consumption was significantly lower

in the lactose intolerants than in tolerant subjects; furthermore, calcium intake was significantly reduced in lactose intolerants. We therefore analyzed the study data, taking into consideration the self-evaluation of the patients of their capacity to digest lactose. Before undergoing the breath test, 49/323 (15%) subjects defined themselves as intolerants to milk and declared that they had eliminated or reduced milk consumption for this reason. This group included three children who were defined “intolerants to milk” by their parents. Of the 49 self-reported milk-intolerant patients, on lactose load and H2 breath test, 26 (53%) were actually lactose maldigesters but did not present any symptoms of lactose intolerance, 5 (10%) were lactose maldigesters and intolerants, and 18 (37%) were lactose digesters and tolerants. The latter 18 subjects were recalled to undergo H2 breath testing after a lactulose load and all showed a normal hydrogen-producing capacity of the intestinal flora. Table 4 shows the demographic characteristics and dietary investigation results in the self-reported milk intolerant subjects compared with the other study subjects. It can be seen that milk consumption was lower in the self-reported milk intolerants than in the other group (p,0.03) and daily calcium intake was also significantly lower (p,0.05). In contrast, there was no difference between the two groups in daily energy intake or consumption of protein.

DISCUSSION Acquired lactase insufficiency may be the cause of gastrointestinal disorders which coincide with milk consumption [1,2,19,20] and this may lead to a reduced consumption in those geographical areas where there is a higher prevalence of lactase insufficiency [5,21]. However, it is known that incapacity to digest lactose is not necessarily associated with clinical symptoms [9 –11]. Furthermore, a recent study showed that most patients who defined themselves milk intolerants did not show any significant worsening of gastrointestinal disorders during the period of lactose-containing milk consumption [12]. The present study is the first to attempt to clarify the dimensions of the problem of self-reported milk-intolerance, the real correspondence between self-reported milk-intolerance

Table 1. Milk and Cheese Consumption, and Daily Intake of Total Calories, Protein and Calcium in the Pediatric Subjects (age range 5 to 16 years), Divided According to the Results of the Breath Hydrogen Test

Milk (ml/day) Cheese (g/day) Total calories Protein (% total kcal) Calcium (mg/day)

Digester-tolerants (n555)

Maldigester-tolerants (n515)

Maldigester-intolerants (n52)

170 (0–1,700) 22.5 (0–150) 2,128 (1,006–2,940) 12.4 (9–15.3) 595 (110–1,310)

165 (0–1,200) 21.5 (0–130) 2,186 (984–2,870) 12.8 (9.2–14) 575 (170–1,118)

50 (0–100)* 30 (0–60) 1,925 (1,520–2,330) 12.2 (9.1–15.3) 300 (150–450)

All dietary data are expressed as median and range. * Digester-tolerants vs. Maldigester-intolerants p,0.03. Maldigester-tolerants vs. Maldigester-intolerants p,0.04.

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Lactose Intolerance and Maldigestion Table 2. Milk and Cheese Consumption, and Daily Intake of Total Calories, Protein and Calcium in the Adult Subjects Studied (Age Range 17 to 64 years), Divided According to the Results of the Breath Hydrogen Test

Milk (ml/day) Cheese (g/day) Total calories Protein (% total kcal) Calcium (mg)

Digesters-tolerants n587

Maldigesters-tolerants n548

Maldigester-intolerants n56

95 (0–800) 50 (0–400) 2,528 (1,850–4,540) 13.1 (9.3–14.5) 615 (150–1,280)

90 (0–600) 45 (0–350) 2,565 (1,720–4,920) 12.9 (9.1–15.5) 605 (160–1,110)

0 (0–0)* 20 (0–150) 2,605 (1,900–4,120) 13.1 (8.9–15.2) 345 (120–600)**

All data are expressed as median and range. * Digester-Tolerants vs. Maldigester-Intolerants p,0.0005. Maldigester-Tolerants vs. Maldigester-Intolerants p,0.005. ** Digester-Tolerants vs. Maldigester-Intolerants p,0.01. Maldigester-Tolerants vs. Maldigester-Intolerants p,0.03.

Table 3. Milk and Cheese Consumption, and Daily Intake of Total Calories, Protein and Calcium, in the Elderly Subjects (Age Range 65 to 85 Years), Divided According to the Results of the Breath Hydrogen Test

Milk (ml/day) Cheese (g/day) Total calories Protein (% total kcal) Calcium (mg)

Digester-tolerants n564

Maldigester-tolerants n541

Maldigester-intolerants n55

105 (0–650) 45 (0–400) 2,230 (1,700–3,820) 13.3 (9.8–15.1) 580 (190–1,210)

90 (0–700) 50 (0–300) 2,310 (1,650–3,700) 13.8 (9.0–14.7) 590 (200–1,190)

0 (0–0)* 25 (0–50) 2,275 (1,820–3,120) 13.4 (9.1–15.3) 344 (125–1,100)**

All data are expressed as median and range. * Digester-Tolerants vs. Maldigester-Intolerants p,0.001. Maldigester-Tolerants vs. Maldigester-Intolerants p,0.005. ** Digester-Tolerants vs. Maldigester-Intolerants p,0.03. Maldigester-Tolerants vs. Maldigester-Intolerants p,0.03.

Table 4. Sex, Age, Milk and Cheese Consumption and Dietary Intake of Total Calories, Protein and Calcium in 49 Self-Reported Milk Intolerant Subjects and in the Other 284 Subjects Studied

Sex (Male/female) Age (years) Milk consumption (ml/day) Cheese (g/day) Total kcal Protein (% total kcal) Calcium (mg/day)

Self-reported milk-intolerants

Self-reported milk-tolerants

18/31 43.6122.1

132/142 43.2125.5

0 (0–50) 30 (0–400) 2,320 (936–4,620) 12.7 (9.3–14.3) 320 (160–1,120)

135 (0–1,700)* 35 (0–400) 2,298 (990–4,920) 12.5 (9–15.3) 585 (110–1,310)**

Age is expressed as mean 6 SD. All dietary data are expressed as median and range. * p,0.03 (Kruskall-Wallis test; z52.18). ** p,0.05 (Kruskall-Wallis test; z51.97).

and gastrointestinal symptoms following the breath hydrogen test, and the impact of this self-diagnosis on dietary intake of total calories, proteins and calcium, using data from the general population and not from a pre-selected sample. In a wide randomized sample representative of a rural community, we observed that 36% of the population were lactose-maldigesters, but only 4% of the whole study group

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(13% of the maldigesters) showed lactose intolerance after an oral load of 25 g lactose. Although many previous studies have reported a much higher frequency of gastrointestinal symptoms after lactose load in subjects with maldigestion [6 – 8,22], it has been underlined [23] how field investigations indicate a greater average tolerance to milk than studies on patients referred to hospitals because of aspecific abdominal complaints [24,25]. Regarding dietary habits, our data show that not all lactose malabsorbers, only the lactose malabsorbers-intolerants, reduce their daily intake of milk; this does not, however lead to a significant variation in dietary intake of total calories but determines a significant variation in calcium intake which is consumed in significantly lower quantities by the lactose-intolerant subjects. Furthermore, it is noteworthy that cheese consumption did not differ between lactose-tolerant and lactoseintolerant subjects. As cheese has relevant calcium content and its consumption does not appear to determine gastrointestinal symptoms, higher dietary intake is advisable in lactose-intolerants. However, as we found a very small number of intolerant patients, it is correct to underline that the difference in milk and calcium intake we observed needs to be confirmed on a larger group of lactose-intolerant subjects. After the cases of self-reported milk intolerants were selected, the analysis of the results is more interesting. The percentage of subjects who believe that they cannot tolerate

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Lactose Intolerance and Maldigestion milk and accordingly reduce milk consumption is considerable: 15% of the examined population. The results of the breath test after lactose challenge were, however, surprising: a) more than 1/3 of these subjects were actually lactose digesters and tolerants (normal H2 breath test and no symptoms following lactose load); b) only 10% of the self-reported lactose-intolerants were really intolerants and showed symptoms after a 25 g lactose load. These results, obtained in a non-selected group of healthy subjects representative of the general population, are in agreement with those recently reported by Suarez et al who showed that 9/30 self-reported lactose intolerants had a normal lactose digestion capacity and that in the remaining 21/30 the gastrointestinal symptoms did not worsen during administration of lactose-containing milk [12]. It is therefore likely that in order to explain the gastrointestinal symptoms of many lactose-maldigesters, the possibility of a diagnosis of irritable bowel syndrome or of non-ulcer dyspepsia [26 –27] should be investigated. Our study also clarifies the impact of self-reported milk intolerance on dietary habits. These subjects did not consume milk, or consumed very low quantities of milk and their daily calcium intake was significantly lower. It must be underlined that in the population we studied daily calcium intake was generally much lower than the recommended level (500 mg vs. 800 –1000 mg/day) [28], and an unnecessary self-limitation of the consumption of a food rich in calcium, as milk is, seems to be a particularly serious risk factor for osteoporosis [29 –31]. In particular, recent prospective studies have suggested that reduced calcium intake during the adolescence and early adulthood may have a great impact on bone mineral density measurements [32,33]; this result must induce physicians to pay particular attention to dietary calcium intake. In conclusion, we affirm that in a representative sample of the general population, with an approximately 40% prevalence of lactase insufficiency, there was: a) a low frequency of lactose intolerance (4%); b) an incongruous overestimation of the frequency of milk intolerance: 15% of the general population; c) a low dietary calcium intake, which is even less satisfactory (300 mg/day) in subjects who limit milk consumption due to self-reported milk intolerance. Lactose digestion capacity should therefore be carefully investigated in all selfreported milk intolerant subjects.

ACKNOWLEDGMENT This work was supported by a grant from the Istituto Danone per la Nutrizione, Italia.

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2. Auricchio S, Rubino A, Landolt M, Semenza G, Prader A: Isolated intestinal lactase deficiency in the adult. Lancet 2:324–326, 1963. 3. Sahi T: The inheritance of selective adult-type lactose malabsorption. Scand J Gastroenterol 30:1–73 (suppl), 1974. 4. Lisker R, Gonzalez B, Daltabuit M: Recessive inheritance of the adult-type of intestinal lactase deficiency. Am J Hum Genet 27: 662–664, 1975. 5. Simoons FJ: The geographic hypothesis and lactose malabsorption: a weighing of the evidence. Am J Dig Dis 23:963–980, 1978. 6. Bayless TM, Rothfeld B, Massa C, Wise L, Paige D, Bedine MS: Lactose and milk intolerance: clinical implications. N Engl J Med 292:1156–1159, 1975. 7. Bedine MS, Bayless TM: Intolerance of small amounts of lactose by individuals with low lactase levels. Gastroenterology 65:735– 743, 1973. 8. Gudmand-Hoyer E, Simony K: Individual sensitivity to lactose in lactose malabsorption. Am J Dig Dis 22:177–181, 1977. 9. Scrimshaw NS, Murray EB: The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance. Am J Clin Nutr 48 (suppl):1079–1159, 1988. 10. Rosado JL, Allen LH, Solomons NW: Milk consumption, symptom response and lactose digestion in milk intolerance. Am J Clin Nutr 45:1457–1460, 1987. 11. Johnson AO, Semenya JG, Buchowski MS, Enwonwu CO, Scrimshaw NS: Correlation of lactose maldigestion, lactose intolerance and milk intolerance. Am J Clin Nutr 57:399–401, 1993. 12. 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 333:1–4, 1995. 13. Montalto G, Muratori R, Soresi M, Carroccio A, Barbagallo CM, Averna MR, Noto D, Ruggeri MI, Bascone F, Cavera G, Notarbartolo A: Prevalence of gallstone disease in small town of Sicily. Eur J Int Med 6:221–226, 1995. 14. Montalto G, Soresi M, Carroccio A, Averna MR, Muratore R, Li Castri C, Barbagallo CM, Cavera G, Sapienza M, Notarbartolo A: Prevalence of biliary lithiasis in elderly people of a small town of Sicily. Age and Aging 21:338–342, 1992. 15. Montalto G, Carroccio A, Soresi M, Cartabellotta A, Lorello D, Cavera G, Averna MR, Barbagallo CM, Anastasi G, Bascone F, Notarbartolo A: Diet and gallstones in women of a rural town of Sicily. J Nutr Envir Med 7:101–106, 1997. 16. Istituto Nazionale della Nutrizione (Italian Institute for Nutrition): “Food Composition Tables.” Rome, 1986. 17. Martini MC, Savaiano DA: Reduced intolerance symptoms from lactose consumed during a meal. Am J Clin Nutr 47:57–60, 1988. 18. Suarez FL, Savaiano DA: Lactose digestion and tolerance in adult and elderly Asian-Americans. Am J Clin Nutr 59:1021–1024, 1994. 19. Dunphi JV, Littman A, Hammond JB, Forstner G, Dahlqvist A, Grane RK: Intestinal lactase deficit in adults. Gastroenterology 49:12–21, 1965. 20. Gudmand-Hoyer E, Dahlqvist A, Jarnum S: The clinical significance of lactose malabsorption. Am J Gastroenterol 53:460–473, 1970. 21. Flatz G: Genetics of lactose digestion in humans. In Harris H, Hirschlorn K (eds): “Advances in Human Genetics.” New York: Plenum Press, pp 1–77, 1987. 22. Jones DV, Latham MC, Kosikowski FV, Woodword G: Symptom

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Received September 1997; revision accepted April 1998.

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