Lactose maldigestion has been under intensive research since its discovery in the 1960's. We know the prevalence of lactose maldigestion in a great number of countries and ethnic groups. However, there is often no provision made for the secondary type of maldigestion, and the study populations have sometimes been selected rather than picked at random. New methods for the measurement of lactose digestion have been developed, and its genetic mechanisms have received a great deal of attention during the last few years. However, in many studies the measurement and/or reporting of symptoms has quite often been overlooked. In this review, various topics related to lactose intolerance are discussed with a special emphasis on its symptoms.
Objectives: Genetically modified lactic acid bacteria may be a way to deliver vaccinal epitopes in the gastrointestinal tract. Aim: Three strains of lactic acid bacteria were studied for their pharmacokinetics in the human gastrointestinal tract. Methods: The survival of the strains was studied up to the ileum in six subjects each, after ingestion of 150 g of fermented milk. The strains and their concentrations in the products were Lactobacillus fermentum KLD (107 cfu/g), Lactobacillus plantarum NCIMB 8826 (108 cfu/g), and Lactococcus lactis MG 1363 (108 cfu/g). Ileal fluid was aspirated by intestinal intubation and immediately cultured. L. plantarum NCIMB 8826, which was found in high concentrations in the ileum, was studied for its survival in the faeces after consumption of 150 g of fermented milk three times daily for 7 days. Faecal samples were collected for culture. Results: The concentration of L. plantarum NCIMB 8826 in the ileum reached 108 cfu/mL after a single dose, with a survival of 7%. L. fermentum KLD and Lc. lactis MG 1363 had lower (0.5 and 1.0%, respectively) and shorter (4 h) survival in the ileum. During the 7‐day ingestion period, L. plantarum NCIMB 8826 reached high concentrations (108 cfu/g) in the faeces, with a survival of 25 ± 29%. None of the strains colonized. Conclusions: L. plantarum NCIMB 8826 has a promising pharmacokinetic profile as a candidate vaccine vehicle.
It has been suggested that the symptoms of irritable bowel syndrome (IBS) may be wrongly attributed to lactose intolerance. We examined the relations among IBS, demographic factors, living habits, and lactose intolerance. On the basis of a lactose tolerance test with ethanol, 101 of the 427 healthy subjects studied were lactose maldigesters and 326 were lactose digesters. IBS was diagnosed by means of the Bowel Disease Questionnaire, according to the Rome criteria. The use of dairy products and symptoms experienced after their consumption were recorded. IBS was found in 15% of both the lactose maldigesters and lactose digesters. One-third of the subjects reported intolerance to dairy products containing < or = 20 g lactose. About half of this third were lactose maldigesters and about half were lactose digesters. As explanations for this subjective lactose intolerance, the logistic regression model estimated lactose maldigestion (odds ratio: 10.3; 95% CI: 5.2, 20.4), IBS (4.6; 2.1, 10.1), experience of symptoms other than gastrointestinal ones (2.3; 1.2, 4.5), and female sex (2.1; 1.1, 4.0). Characteristics common to both subjective lactose intolerance and IBS were female sex and the experience of abdominal pain in childhood (P < 0.01). Age, regularity of meals, and the amount of physical activity were not associated with either subjective lactose intolerance or IBS. Of the subjects with IBS, the percentage of lactose maldigesters was the same as in the whole study group (24%) but the number who reported lactose intolerance was higher (60% compared with 27%, P < 0.001). We showed a strong relation among subjective lactose intolerance, IBS, the experience of abdominal pain in childhood, and female sex.
In this study we examined whether small doses of lactose induced symptoms in 39 lactose maldigesters and 15 lactose digesters in a randomized, crossover, double-blind design. The test doses were 200 mL fat-free, lactose-free milk to which 0, 0.5, 1.5, and 7 g lactose was added. Every third day of a lactose-free diet, after an overnight fast, the subjects drank one of the test milks in random order and registered the occurrence and severity of gastrointestinal symptoms in the next 12 h. During the study, the maldigesters reported significantly more abdominal bloating (P = 0.0003) and abdominal pain (P = 0.006) than the digesters. There was no difference in the mean severity of the reported symptoms between the test milks and the lactose-free milk in the group of lactose maldigesters, of whom one-third did not experience any symptoms from any of the test doses. The same proportion (64%) of the maldigesters experienced symptoms after both the lactose-free milk and the milk with 7 g lactose. However, the symptoms occurred inconsistently with the different test doses in 59% of the maldigesters. Thus, it can be concluded that the gastrointestinal symptoms in most lactose maldigesters are not induced by lactose when small amounts (0.5-7.0 g) of lactose are included in the diet.
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Probiotics or biotherapeutic agents can influence physiology through direct or indirect effects occurring in the gastrointestinal tract. Knowledge on their pharmacokinetics is needed 1) to answer the questions how much probiotic should be consumed?, how often?, how long?; 2) to correlate the effects with the concentration of the probiotic at the target site; 3) to validate hypotheses such as "a probiotic should be of human origin, ... have a high survival capacity, ... adhere to the intestinal epithelium" ...; 4) to anticipate the effects of other probiotics; 5) to establish what concentrations should be present in the commercial preparations; 6) for safety. Some in vitro models have been developed to predict the survival of probiotics in vivo or their adherence to the intestinal epithelium, however, the best way to establish the pharmacokinetics of a probiotic is to measure it in vivo. Three techniques can be used: collection of feces, pixigraphy, and intestinal intubation. The use of transit markers such as spores of Bacillus stearothermophilus is necessary to study the potential for probiotics to colonize (i.e. to persist for longer period than the inert marker). Knowledge on the pharmacokinetics of probiotics is reviewed. Some strains can adhere to cell lines such as CaCo2 or HT29. The survival of ingested probiotics differs greatly between genus and strains. Some strains are rapidly destroyed in the stomach while others such as some Bifidobacterium sp. or Lactobacillus sp. survive till feces.
Lactose digestion improves when the energy content of a meal is raised, perhaps due to delayed gastric emptying; however, this has not been demonstrated directly. It is not known whether lactose-intolerant subjects should consume full-fat or high energy milk instead of half-skimmed milk. In this study, breath 13CO2 and hydrogen (H2) measurements were combined to assess simultaneously the effect of increasing milk energy content on gastric emptying, digestion, and tolerance of lactose. On two separate days, 11 adult lactose maldigesters ingested, in the fasting state, a single dose of 710 kJ half-skimmed milk or 1970 kJ high energy milk. Both contained 18 g lactose and were supplemented with 100 mg 13C-glycine for breath 13CO2 measurement. For 6 h after milk ingestion, samples of expired breath were collected, and subjects scored their symptoms on a four-grade questionnaire. Gastric emptying was measured from excretion of breath 13CO2. The mean gastric emptying half-time was significantly longer after ingestion of high energy milk than after half-skimmed milk (84 +/- 4 vs. 64 +/- 4 min, P = 0.004). The mean area under the breath H2 excretion curve measured for 6 h was 330 +/- 61 microL/L after subjects consumed high energy milk vs. 470 +/- 82 microL/L after they consumed half-skimmed milk (P = 0.07). Mean symptom scores did not differ after ingestion of the two milks, but only two subjects experienced disturbing symptoms after high energy milk ingestion compared with five subjects after ingestion of half-skimmed milk (P = 0.56). Although ingestion of high energy milk delayed the gastric emptying of lactose for significantly longer than the ingestion of half-skimmed milk (P < 0.01), it did not lead to significant improvement in symptoms and reflected only a trend toward improved lactose digestion (P = 0.07), as measured by the area under the breath H2 excretion curve. These results indicate that it is not beneficial for most lactose-intolerant subjects to replace consumption of half-skimmed milk by milk with a higher energy content.
The possibility of delaying gastric emptying and improving lactose digestion and tolerance by increasing milk viscosity was studied in 13 lactose maldigesters who ingested three test milks with different viscosities (range: 33-1892 mPa.s) in random order at intervals of 1 wk. Each test portion was 500 mL and provided approximately equal to 1900 kJ and 18 g lactose. The different viscosities were obtained by adding varying proportions of rice starch and maltodextrin to a basic milk formula. A combined [13C]glycine-hydrogen breath test was used to measure gastric emptying and lactose digestion simultaneously. Participants reported their gastrointestinal symptoms by using a four-grade scale. Mean (+/- SEM) gastric-emptying half times were 78 +/- 5.7 min for low-viscosity milk (30 mPa.s), 86 +/- 5.0 min for moderate-viscosity milk (80 mPa.s), and 78 +/- 4.5 min for high-viscosity milk (1.9.10(3) mPa.s). Mean orocecal transit times (180 +/- 24, 163 +/- 23, and 180 +/- 24 min, respectively) were not significantly different. There were no milk-dependent differences in breath-hydrogen excretion or in the severity of gastrointestinal symptoms. The milks were well tolerated; > 50% of the subjects reported nondisturbing symptoms or none. We conclude that gastric emptying, orocecal transit time, and lactose digestion and tolerance were not affected by altering milk viscosity. This may have been due to the high energy content of the test milks, which in itself led to slow gastric emptying.
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