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beyond reason
현대의학의 선배 탐구자에게 감사와 존경을!!
어떤 사람에게는 좋은 음식이 어떤 사람에게는 독이 된다.
우유의 락토스 소화효소가 없는 사람들이 우유를 먹으면 장누수가 생긴다
근육검사
1) 락토스를 소화시키는 락타제 효소를 먹으면 유제품은 자유롭게 먹어도 된다 - yes
2) 아래 논문과 같은 우유를 먹을 수 있는 치료를 한 후 유제품을 먹는 것은 좋은 선택이다 - yes
World J Gastroenterol. 2006 Jan 14; 12(2): 187–191.
Lactose malabsorption is a very common condition characterized by intestinal lactase deficiency. Primary lactose malabsorption is an inherited deficit present in the majority of the world’s population, while secondary hypolactasia can be the consequence of an intestinal disease. The presence of malabsorbed lactose in the colonic lumen causes gastrointestinal symptoms. The condition is known as lactose intolerance.
In patients with lactase nonpersistence, treatment should be considered exclusively if intolerance symptoms are present. In the absence of guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages.
Several studies have been carried out to find alternative approaches, such as exogenous β-galactosidase, yogurt and probiotics for their bacterial lactase activity, pharmacological and non pharmacological strategies that can prolong contact time between enzyme and substrate delaying gastrointestinal transit time, and chronic lactose ingestion to enhance colonic adaptation. In this review the usefulness of these approaches is discussed and a therapeutic management with a flow chart is proposed.
Lactose malabsorption is a very common condition characterized by lactase deficiency, an enzyme occurring in the brush border membrane of the intestinal mucosa that hydrolyzes lactose to its components galactose and glucose [1]. High concentrations of this enzyme are physiologically present in neonates. Post weaning, a genetically programmed and irreversible reduction of its activity occurs in the majority of the world’s population [2] which results in primary lactose malabsorption. Secondary hypolactasia can be the consequence of any condition that damages the small intestinal mucosa brush border or significantly increases the gastrointestinal transit time. Thus, secondary hypolactasia is transient and reversible [3].
The presence of malabsorbed lactose in the colonic lumen does not necessarily result in gastrointestinal symptoms. Only when lactose malabsorption is associated with clinical manifestations as bloating, flatulence, abdominal pain and diarrhea, “lactose intolerance” occurs [4].
Diagnosis of lactose intolerance is often made on a clinical basis and in response to an empirical trial of dietary lactose avoidance. A number of methods are available to diagnose lactose malabsorption [4-8]. The lactose breath hydrogen test is nowadays considered a very simple and useful test in subjects with suspected lactose malabsorption. Undigested lactose is fermented by the colonic microflora with production of hydrogen detectable in pulmonary excretion [6]. Direct lactase enzyme activity performed on small intestinal tissue biopsy samples may be utilized, but it is an invasive procedure and its reliability can be low because disaccharidase activity in a small biopsy specimen does not necessarily reflect the jejunal activity as a whole [4]. Recent evidence suggests that a genetic test of the -13910 C/T polymorphism can be used as the first stage screening test for adult-type hypolactasia [9,10].
In patients with lactase nonpersistence, treatment is considered exclusively in the presence of intolerance symptoms [11]. In the absence of guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages, chiefly for reduced intake of substances such as calcium, phosphorus and vitamins, and may be associated with decreased bone mineral density [12,13]. To overcome these limits, several studies have been carried out to find alternative approaches, such as exogenous β-galactosidase, yogurt and probiotics for their bacterial lactase activity, pharmacological and non pharmacological strategies that can prolong contact time between enzyme and substrate delaying gastrointestinal transit time, and chronic lactose ingestion to enhance colonic adaptation.
Enzyme-replacement therapy with microbial exogenous lactase (obtained from yeasts or fungi) represents a possible strategy for primary lactase deficiency. Enzymes can be added in a liquid form to milk before its consumption or administered in a solid form (capsules or tablets) together with milk and dairy products. Several studies were conducted adding the soluble enzyme to milk some hours before its consumption, thus obtaining a “preincubated milk” [9,14-17]. This strategy is effective in reducing both H2 breath excretion and subjective manifestations of discomfort after milk ingestion. However, these trials were carried out on relatively small series populations. They were not placebo-controlled, and results were not comparable since there was a lack of homogeneity in patient subsets. Furthermore, preincubated milk was not considered practical because of the necessity to add the enzyme some hours before its consumption. The low-lactose milk is a preincubated milk in which the lactose is already pre-hydrolyzed; this product is commercially available but not distributed everywhere (i.e. restaurant, cafeterias, etc). To obviate these problems, several studies have been carried out to show the effectiveness of replacement therapy even when lactase is administered at mealtime [18-22].
In a recent double-blind, placebo-controlled crossover study in 30 intolerant subjects with lactose malabsorption, we showed that both “preincubated milk” and milk treated at mealtime are similarly able to significantly reduce H2 excretion and symptom score, suggesting that enzymes can be used at mealtime because of its better practicality [23].
While the efficacy of liquid exogenous lactase in reducing both H2 excretion and symptoms is widely emphasized, results about the exact rate of efficacy are somehow discordant. Several factors may justify these discrepancies. The different enzyme origin can play a role. It is well-known that, at the same dose, enzymes obtained from different microorganisms have different efficacy in hydrolyzing lactose. In fact, comparative studies have already shown the higher efficacy of lactase derived from K. lactis than that of the enzyme obtained from A. niger [5,19]. The contribution of residual intestinal mucosal lactase activity should also be considered to explain the variation in intolerance symptoms experienced by lactose malabsorbers. The results of non crossover studies without considering intra-individual variables can be biased, if the residual intestinal mucosal enzyme activity is ignored. Moreover, the different dosage of the enzyme could be another influencing factor. In fact, it is known that a close relationship exists between the amount of lactose to be hydrolyzed and the enzyme units required [5,21]. Moreover, the stomach pH and bile salt concentrations could influence the efficacy of exogenous lactase.
Solid lactase preparations, in capsules and tablets, are commercially available alternatives for enzyme-replacement therapy. Several studies have investigated and confirmed their efficacy [25-26]. However, comparative studies have shown that these preparations are more expensive and significantly less effective than prehydrolyzed milk probably due to the enzyme gastric inactivation [11,17]. Their use can be suggested for solid dairy products.
Therapy compliance with β-galactosidase is assured by good palatability [16,21,23] though there are some reported taste alterations [27]. The safety of lactase preparations has recently been confirmed [28]. In conclusion, the addition of exogenous lactase, especially at mealtime, seems to be effective, practical and with no side effects.
It is well-known that fermented milk products improve lactose digestion and symptoms of intolerance in lactose maldigesters [17,29,30]. Onwulata et al [17] demonstrated that commercially available plain yogurt is as effective in reducing H2 and symptoms as prehydrolyzed milk. The use of fermented milk is based on the presence of endogenous lactase activity of yogurt microorganisms. Yogurt is made of milk incubated mainly with two species of lactic acid bacteria, L. bulgaricus and S. thermophilus [29,31]. These microorganisms participate in lactose hydrolysis both during fermentation processes and after lactose ingestion [32-34]. It has been calculated that fermentation decreases lactose content by approximately 25-50% [33-34]. At the same time, this process results in an acid taste and just for this tartness several subjects dislike yogurt. To overcome this limit, the addition of high concentrations of viable L. acidophilus to cold milk has been proposed as an alternative to yogurt, obtaining an unfermented milk (sweet acidophilus milk). However, in a comparative crossover study carried out in eleven lactose malabsorbers, Payne et al [5] first demonstrated that sweet acidophilus milk does not reduce H2 excretion and symptoms significantly as milk treated with a commercial lactase preparation. Further studies have confirmed the inadequate effectiveness of sweet acidophilus milk [17,33,35]. To explain these findings, it has been proposed that bacterial lactase in sweet acidophilus milk is insufficient to show a measurable effect or is not easily available in the intestinal lumen, becoming accessible only if disruption of the cell membrane occurs [30,33]. In fact, the cell membrane structures of lactic acid bacteria play a key role in the availability of β-galactosidase [17,36]. Lin et al [37] compared L. bulgaricus and L. acidophilus, two termophilic bacteria with similar β-galactosidase activity, bile sensitivity and active transport system for lactose, while differing in the resistance of the cell wall membrane structures, as shown by sonication time for maximum β-galactosidase activity measurements. By measuring H2 excretion and clinical score, they found that L. bulgaricus is a better choice for manufacturing non fermented milk products, because the cell wall membrane structures of L. bulgaricus are less tough than those of L. acidophilus, with a consequent better ability to release the enzyme.
To effectively release β-galactosidase, bacteria need an intact cell wall as mechanical protection of the enzyme during gastric passage and against the action of bile [38]. It was demonstrated that gastric acid degrades bacterial lactase activity in 20-60 min [39]. However, the association of L. acidophilus BG2F04with omeprazole does not result in reduced hydrogen production and gastrointestinal symptoms are not improved after lactose ingestion with respect to lactobacilli without it [40]. These results could have been due to the selected lactic bacteria. In fact, it is well-known that lactobacilli behave differently depending on the species [41,42]. As recently demonstrated, administration of the multiprobiotic product VSL3 cannot reduce H2 excretion and clinical score [43]. Further investigations are necessary to clarify the probiotics role in lactose intolerance therapy, also considering their well-known beneficial effects on intestinal functions, gas metabolism and motility [38].
The bacterial β-galactosidase activity of yogurt is considered to be the main factor responsible for improving lactose digestion; its greater osmolality and energy density can also play a role [38]. Yogurt delays gastric emptying and intestinal transit causing slower delivery of lactose to the intestine, thus optimizing the action of residual β-galactosidase in the small bowel and decreasing the osmotic load of lactose[3,38].
Leichter et al [44] showed that full-fat milk (high energy milk) increase lactose tolerance compared to skimmed milk and aqueous lactose solution. It has been reported that fat improves carbohydrate absorption slowing down gastric emptying and intestinal transit time with a consequent prolongation of contact time between enzyme and substrate [45-47]. Other studies have not confirmed these results [48,49]. In particular, Vesa et al [49] have proved that the ingestion of high energy milk delays more significantly gastric emptying than half-skimmed milk but it does not result in a significant improvement in lactose tolerance. To improve lactose digestion by delaying gastric emptying, co-ingestion of food together with dairy products has also been proposed, and it has been demonstrated that lactose is better tolerated when taken with other foods [19,50].
Pharmacological approaches that can modify gastric emptying and intestinal transit have also been considered. A double-blind randomized cross-over placebo-controlled study [51] evaluated the effect of propantheline and metoclopramide on lactose digestion, and found that propantheline-induced prolongation of gastric emptying improves lactose tolerance as measured by reduced symptoms and H2 breath concentration compared to placebo or metoclopramide. Loperamide has been proposed for its activity on oral-cecal transit time. Szilagy et al [52] demonstrated that loperamide improves H2 excretion and symptoms when administered together with milk. Later on, the authors concluded that the use of loperamide is not advisable because of its side-effects and high cost [53].
Lactase is a non inducible enzyme [1], but it was also reported that continuous lactose consumption decreases hydrogen excretion and the severity of gastrointestinal symptoms [54-58]. Decreased hydrogen excretion is not necessarily the consequence of increased lactose digestion but can depend on adaptative phenomena. This “adaptation” is associated with changes in gut microflora as well as in some colonic functions and features. The increased microbial β-galactosidase activity is one of the hypothesized mechanisms. Hertzler et al [59] showed that fecal β-galactosidase activity is increased after daily milk feeding for 10 d. However, the lower H2 production is not related to higher levels of lactase in the existing flora. It has been suggested that changes in the intestinal microflora could decrease hydrogen production and/or increase intestinal gas consumption [60]. Hill et al [61] have proved that malabsorbed lactose enhances the fermentation ability of bifidobacteria and other lactic acid bacteria which can metabolize lactose without hydrogen production. Perman et al [62] hypothesized that the reduction of colonic pH due to the fermentation of malabsorbed lactose affects bacterial metabolism and inhibits hydrogen production. The placebo effect has been suggested as an additional factor to explain the adaptation in response to continuous lactose ingestion. In a controlled double-blind study, Briet et al [59] have demonstrated increased fecal β-galactosidase, reduced H2 excretion and improved symptoms after lactose ingestion for 13 d. However, in the control group with sucrose, no sign of metabolic adaptation could be found except for a reduced clinical score, suggesting a placebo effect.
We suggest a flow chart for the therapeutic management of lactose malabsorption considering data gathered from literature and our personal experience (Figure (Figure1).1). We underline that not all subjects with lactase deficit have to be treated, but just symptomatic ones, since there are no known adverse effects of lactose maldigestion other than acute gastrointestinal symptoms [11]. Furthermore, most lactose-intolerant people can ingest 12 g/d of lactose (equivalent to one cup of milk), without experiencing adverse symptoms [63-64].
It is necessary to distinguish between primary and secondary lactase deficit. In the secondary form a temporary lactose-free diet is necessary only until a complete recovery of the causative pathological condition is obtained. Lactose breath test can be advised to verify the recovered enzymatic activity. In primary hypolactasia, a different therapeutic strategy should be considered because of the irreversibility of the condition. Initially, a temporary avoidance of milk and dairy products from the diet should be indicated to obtain symptom remission. Subsequently, we suggest a gradual re-introduction of dairy products considering the individual threshold dose, to assure an adequate intake of essential nutritional substances. In order to raise the threshold dose, some non-pharmacological and pharmacological strategies should be considered. Changes in dietary habits, as the ingestion of milk together with other foods such as brioches, cookies and cake, and the consumption of fermented and matured dairy products can assure an adequate milk intake while preventing the onset of intolerance symptoms. Chronic consumption of milk seems to be useful to favorite the adaptation. Considering the dose-dependent lactose absorption, we suggest the distribution of the daily milk amount in small meals. If these strategies fail to reduce lactose intolerance, some pharmacological therapies are available. The addition of exogenous lactase in a liquid form to milk at mealtime has been demonstrated effective and practical. Pre-hydrolyzed milk preparations (i.e. on sale low-lactose content milk) could also be advisable. β-galactosidase tablets or capsules are suitable only for consumption of solid dairy products. Based on the literature data no other pharmacological strategies can be suggested. A pharmacological support of calcium and vitamins is required independently of the chosen therapeutic approach if the daily intake of dairy products is not assured.
64. Vonk RJ, Priebe MG, Koetse HA, Stellaard F, Lenoir-Wijnkoop I, Antoine JM, Zhong Y, Huang CY. Lactose intolerance: analysis of underlying factors. Eur J Clin Invest. 2003;33:70–75. [PubMed] [Google Scholar]
Double-blind, placebo-controlled, crossover study.
University Hospital.
In total, 11 male and 19 female (aged from 18 to 65 y, mean age 43.3 y) lactose malabsorbers with intolerance participated.
Each patient underwent three H2 breath tests, in a random order. We used 400 ml of cow's semiskimmed milk as substrate and a β-galactosidase obtained from K. lactis. The test A was carried out adding to the milk the enzyme (3000 UI), 10 h before its consumption; the test B was performed adding the β-galactosidase (6000 UI) 5 min before milk ingestion and the test C was made using placebo. We evaluated the maximum breath H2 concentration, the cumulative H2 excretion and a clinical score based on intolerance symptoms (bloating, abdominal pain, flatulence and diarrhoea).
Our study showed a significant reduction of the mean maximum H2concentration after both test A (12.07±7.8 p.p.m.) and test B (13.97±7.99 p.p.m.) compared with test C (51.46±16.12 p.p.m.) (ANOVA F=54.33, P<0.001). Similarly, there was a significant reduction of the mean cumulative H2 excretion after both test A (1428±1156 p.p.m.) and test B (1761±966 p.p.m.) compared with test C (5795±2707 p.p.m.) (ANOVA F=31.46, P<0.001). We also observed a significant reduction of the mean clinical score after both test A (0.36±0.55) and test B (0.96±0.85) compared with test C (3.7±0.79) (ANOVA F=106.81, P<0.001). Moreover, with regard to the mean clinical score, there was a significant reduction after test A with respect to test B (Bonferroni's P=0.03).
Our study shows that in lactose malabsorbers with intolerance, the lactase obtained from K. lactis can represent a valid therapeutic strategy, with objective and subjective efficacy and without side effects.
Lactose malabsorption is characterised by deficiency of lactase, an intestinal enzyme that hydrolyses lactose to its components galactose and glucose (Gilat et al, 1972). It is a very common condition, reaching 70% in southern Italy (Gudmand-Hoyer, 1994). High concentrations of lactase are physiologically present in neonates; nevertheless, postweaning, a genetically programmed and irreversible reduction of its activity occurs in the majority of the world's population (Wang et al, 1998).
The presence in the colonic lumen of malabsorbed lactose does not necessarily result in gastrointestinal symptoms. When this condition is related to uncomfortable clinical manifestations as bloating, abdominal pain and diarrhoea, ‘lactose intolerance’ occurs (Shaw & Davies, 1999). Worldwide, up to 50% of malabsorbers exhibits symptoms (Rosado et al, 1984). Nowadays, the usual behaviour for this condition consists of the avoidance of milk and dairy products from the diet. However, this restriction leads to a reduction of intake of substances such as calcium, phosphorus and vitamins, and may associate with decreased bone mineral density (Solomons et al, 1985a, 1985b; Di Stefano et al, 2002). To overcome these limits, in the last years, several approaches have been studied: drugs that increase contact time between enzyme and substrate, either delaying orocoecal transit (ie loperamide) (Szilagyi et al, 1996, 2000) or delaying gastric emptying (ie propantheline) (Peuhkuri et al, 1999); continuous lactose consumption to induce colonic adaptation (Briet et al, 1997); substitutes for milk (Swagerty et al, 2002); yogurt and probiotics for their bacterial β-galactosidase activity (Onwulata et al, 1989; Saltzman et al, 1999); addition of exogenous lactase to the milk before its consumption (Solomons et al, 1985a, 1985b; Barillas & Solomons, 1987; Corazza et al, 1992; Lin et al, 1993). In particular, replacement therapy resulted in an efficacious strategy; nevertheless, only few double-blind and/or placebo-controlled trials have been performed.
We have evaluated, in a double-blind, placebo-controlled, crossover study, the efficacy of the addition to the milk, 10 h and 5 min before its consumption, of lactase obtained from Kluyveromyces lactis in lactose malabsorbers with intolerance.
We enrolled 30 patients (11 male, 19 female; aged from 18 to 65 y, mean age 43.3 y), referred to our Day Hospital of Internal Medicine and Gastroenterology because of symptoms compatible with lactose intolerance, and who were lactose H2 breath test positive. Each patient underwent, in a random order, three H2 breath tests. An interval of at least 72 h was allowed among successive tests, to avoid the effect of colonic acidification. We used 400 ml of cow's semiskimmed milk as substrate (containing about 20 g of lactose), and a β-galactosidase obtained from K. lactis (Silact, Sofar SpA, Trezzano Rosa, MI, Italy).
The test A was performed adding the enzyme to the milk, with mild mixing, 10 h before its consumption (preincubated): the temperature of milk during incubation was 4°C; the test B was carried out adding the β-galactosidase 5 min before milk ingestion (mealtime) and the test C was made using placebo.
Concentration of β-galactosidase was 5000 U/ml; 0.3 ml corresponds to 1 drop of used enzyme. While in test A, we used 3000 U (2 drops) of lactase, and in test B we added 6000 U (4 drops). These quantities were chosen considering the units able to hydrolyse, in the two different preparations, at least 70% of present lactose, as suggested by the manufacturer. One neutral lactase unit is the quantity of enzyme that incubated at 25°C and pH 7.5 with o-nitrophenyl-β-D-galactopyranoside produces 1 μmol of o-nitrophenyl per minute. Test C was performed using aspartame, a sweetening substance not able to digest milk, because galactose and glucose are more sweet than intact lactose.
An investigator prepared milk with either enzyme or placebo in numbered containers, identical in shape and colour. Another blinded investigator administered treated milk to the patients. Enrolled subjects did not have any information about the content of milk.
The evening before the test, all subjects consumed a meal of only rice, meat and olive oil to avoid the probable influence, on the basal H2values, of a prolonged gas production due to the presence of nonabsorbable or slowly fermentable material in the colonic lumen. After an overnight fast, and a mouthwash with chlorhexidine to eliminate the possible early hydrogen peak due to the fermentation of the ingested sugar by oropharyngeal bacteria, patients received the milk with either enzyme or placebo. Smoking and physical exercise were forbidden 1 h before and throughout the test. Sampling of alveolar air was performed by means of a commercial device, which allows the first 500 ml of dead space air to be separated and discarded, while the remaining 700 ml of end-alveolar air is collected in a gas-tight bag (Gasampler Quintron, Milwaukee, WI, USA). Subjects were instructed to avoid deep inspiration and not to hyperventilate before exhalation.
For the analysis of H2 concentration in air samples, we used a dedicated gas chromatograph (Model 12i, Quintron Instrument, Milwaukee, WI, USA). Breath samples were taken at fasting and every 30 min for 4 h after milk ingestion. Hydrogen concentrations were expressed in parts per million (p.p.m.). An increase in H2 concentration of at least 20 p.p.m. above the basal value was considered indicative of lactose malabsorption. We evaluated the maximum H2 concentration and the cumulative H2 excretion, the latter obtained using the formula for the sum of areas of consecutive trapezoids, in accordance with Kotler et al (1982).
For 8 h following milk ingestion, all subjects kept a diary where they recorded the eventual occurrence of intolerance symptoms whose severity was indicated by a score. Considered symptoms were bloating (absent=0; mild=1; moderate=2; severe=3), abdominal pain (absent=0; mild=1; moderate=2; severe=3), flatulence (absent=0; mild=1; moderate=2; severe=3) and diarrhoea (absent=0; present=3). For every patient, a cumulative index was calculated by the sum of the partial score of each symptom. Obtained data were collected by a blinded investigator and were analysed by a blinded statistician.
Statistical analysis was performed by means of one-way analysis of variance (ANOVA). Post hoc comparison was assessed with Bonferroni's correction. A P-value of 0.05 or less was considered significant. Data are expressed as mean±standard deviation (s.d.).
No statistical difference was found among the baseline H2-concentration before test A (2.77±1.98), test B (2.7±1.6) and test C (4.31±3.4) (ANOVA F=5.05, P=0.008). Our study showed a significant reduction of the mean maximum H2 concentration after the addition of lactase to milk, respectively, 10 h (12.07±7.8 p.p.m.) and 5 min (13.97± 7.99 p.p.m.) before its consumption with respect to placebo (51.46±16.12 p.p.m.) (ANOVA F=54.33, P<0.001) (Figure 1); the reduction percentage was 77 and 73%, respectively.
Similarly, there was a significant reduction of the mean cumulative H2excretion when the lactase was added to milk both 10 h (1428±1156 p.p.m.) and 5 min (1761±966 p.p.m.) before its consumption with respect to placebo (5795±2707 p.p.m.) (ANOVA F=31.46, P<0.001) (Figure 2); the reduction percentage was 76 and 70%, respectively.
The curves of breath hydrogen displaying half-hour intervals with mean (±s.d.) obtained in test A, test B and test C are shown in Figure 3.
We also observed a significant reduction of mean clinical score after the addition of lactase to milk either 10 h (0.36±0.55) or 5 min (0.96±0.85) before its consumption compared with placebo (3.7±0.79) (ANOVA F=106.81, P<0.001) (Figure 4); the reduction percentage was 90 and 75%, respectively.
Finally, no differences in the mean maximum H2 concentration and in the mean cumulative H2 excretion were found with preincubated milk or adding enzyme at mealtime (Figures 1 and 2); instead, about the mean clinical score, there was a significant reduction when lactase was added 10 h rather than 5 min before milk consumption (Bonferroni's P=0.03 group A vs group B) (Figure 4).
The use of exogenous β-galactosidase in lactose malabsorbers was shown to be efficacious and without any side effects. Initially, this approach was judged as not practical because of the necessity to add the enzyme some hours before milk consumption (Rask Pedersen et al, 1982; Onwulata et al, 1989; Lin et al, 1993). Other studies, carried out to resolve this matter, have demonstrated the efficacy of the lactase also when added at mealtime (Solomons et al, 1985a, 1985b; Barillas & Solomons, 1987; Corazza et al, 1992). Nevertheless, until now just a few double-blind and/or placebo-controlled trials have been performed. For this reason, although replacement therapy with lactase does not represent a novel strategy, we designed a double-blind, placebo-controlled, crossover study using two different prehydrolysed preparations obtained adding exogenous lactase 10 h before or at mealtime.
We found a significant reduction of the H2 production and symptoms score when the milk was prehydrolysed by β-galactosidase with respect to placebo. In particular, both preparations were efficacious in reducing the mean maximum H2 concentration and the mean cumulative H2excretion. These results do not fully resemble the previous studies and this can be explained by some observations: firstly, by the different enzyme origin. Comparative studies had already shown the major efficacy of the lactase derived from K. lactis with respect to the enzyme obtained from Aspergillus niger (Rosado et al, 1984; Solomons et al, 1985a, 1985b). In this way, we could explain the results obtained by Corazza et al. In fact, they added a lactase derived from A. niger to the milk at mealtime and obtained a lower reduction both of maximum H2concentration (about 38%) and cumulative H2 excretion (about 43%) than us (Corazza et al, 1992). The dose of enzyme is another factor that should be considered. Lami et al (1988), in a double-blind study, found a percentage reduction of the H2 maximal peak of about 39% if 2000 UI of lactase from K. lactis was added at mealtime, and of about 58% when 1000 UI of the same enzyme was added 12 h before milk consumption. We can speculate that a linear relationship exists between the dose of lactose and the units of β-galactosidase required to improve digestion. So, our better results could be explained by the three-fold quantity of lactase that we used.
Also regarding clinical aspects, our study showed very satisfactory results. In particular, we found a significantly symptoms score reduction of both milk-lactase preparations compared with placebo; moreover, we have found a slight significant improvement when lactase was added 10 h rather than 5 min before milk consumption. It is not easy to explain the significance of this difference about subjective parameter. In our opinion, despite this little difference, we can advise the use of the enzyme also at mealtime, because of its greater practicality.
The clinical aspect should be considered more relevant than the H2excretion; in fact, in malabsorber patients with intolerance, since there are no known adverse effects of lactose maldigestion other than acute gastrointestinal symptoms, the major end point is to resolve the clinical picture. Just for this reason, the treatment is reserved exclusively for intolerant subjects (Suarez et al, 1995). Moreover, there is emerging evidence that malabsorbed lactose could act as a prebiotic and so could be beneficial against some lower intestinal diseases (Szilagyi, 2002).
Low-lactose/lactose-free products should be strongly suggested in malabsorber patients with intolerance to avoid the common behaviour of limiting intake of milk and dairy products. Certainly, the already on-sale lactose-free milk is more practical than addition of exogenous β-galactosidase. On the other hand, the possibility to use the lactase makes feasible milk consumption also when lactose-free milk is not available and when intolerant subjects are away from home (ie restaurant, cafeterias, home of friends, etc.). Moreover, other commercially available preparations of lactase (in capsules or tablets) could be very useful and easy to use, overall for solid dairy products. Nevertheless, previous studies have shown that these preparations were less effective than prehydrolysed milk, probably because of gastric inactivation of the enzyme (Onwulata et al, 1989), and more expensive (Suarez et al, 1995).
Finally, even though our diary was not specifically addressed to evaluate the palatability, none of our patients reported about taste alteration of the milk treated with exogenous lactase, as previously described (Onwulata et al, 1989).
In lactose malabsorbers with intolerance, the use of the prehydrolysed milk with the β-galactosidase obtained from K. lactis results in an effective and rational therapeutic approach, accepted by patients, without side effects, with objective satisfactory results (reduction of H2excretion) and with reduction of the gastrointestinal symptoms.
Barillas C & Solomons NW (1987): Effective reduction of lactose maldigestion in preschool children by direct addition of b-galactosidase to milk at mealtime. Pediatrics 79, 766–772.
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