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Fructooligosaccharides and lactulose cause more symptoms in lactose maldigesters and subjects with pseudohypolactasia than in control lactose digesters.

BACKGROUND: Many lactose maldigesters tolerate more lactose in experimental studies than in everyday life, in which their symptoms may result from other carbohydrates as well. OBJECTIVE: The question of whether the symptoms caused by large quantities of carbohydrates are more severe in lactose maldigesters than in control lactose digesters or in lactose digesters who report milk to be the cause of their gastrointestinal symptoms (pseudohypolactasic subjects) was studied in a randomized, double-blind, crossover study. Comparisons between commonly used diagnostic methods for lactose maldigestion were also made. DESIGN: The subjects were 40 women aged 20-63 y from 3 groups: lactose maldigesters (n = 12), pseudohypolactasic subjects (n = 15), and control lactose digesters (n = 13). The subjects were given either 50 g lactose, 50 g sucrose, 25 g lactulose, or 25 g fructooligosaccharides. After carbohydrate ingestion, urine was collected and the breath-hydrogen concentration was measured every 30 min for 3 h. Blood glucose was measured every 20 min for 1 h and subjective gastrointestinal symptoms were monitored for 8 h with a questionnaire. RESULTS: When lactulose and fructooligosaccharides were ingested, the lactose maldigesters (P = 0.04 and 0.09, respectively) and the pseudohypolactasic subjects (P = 0.006 and 0.01, respectively) reported more symptoms than did the control lactose digesters. Sucrose caused more symptoms in the lactose maldigesters than in the control lactose digesters (P = 0.05). CONCLUSIONS: Lactose maldigesters and lactose digesters with pseudohypolactasia experience more symptoms than control lactose digesters after a single intake of large amounts of indigestible carbohydrates. Lactose maldigesters also experience more symptoms after ingesting sucrose.

Adult↗

Chronic consumption of fresh but not heated yogurt improves breath-hydrogen status and short-chain fatty acid profiles: a controlled study in healthy men with or without lactose maldigestion.

BACKGROUND: Ingestion of fermented dairy products induces changes in the equilibrium and metabolism of the intestinal microflora and may thus have beneficial effects on the host. OBJECTIVE: We compared the effects of chronic consumption of yogurt with (fresh) or without (heated) live bacterial cultures (Lactobacillus bulgaricus and Streptococcus thermophilus) on plasma glucose, insulin, triacylglycerols, cholesterol, fatty acids, and short-chain fatty acids. DESIGN: Two groups of 12 healthy men with or without lactose malabsorption were selected with use of a breath-hydrogen test after a 30-g lactose load. Subjects were randomly assigned in a crossover design to 500 g/d of either fresh or heated yogurt for 2 periods of 15 d each, separated by a 15-d washout interval. RESULTS: Chronic consumption of fresh or heated yogurt had no detrimental effects on plasma glucose, insulin, or fatty acid areas under the curve in response to acute ingestion of 500 g yogurt in healthy men with or without lactose malabsorption. There were also no detectable changes in fasting plasma glucose, insulin, fatty acid, triacylglycerol, or cholesterol concentrations. In contrast, plasma butyrate was higher (P: < 0.03) and plasma propionate tended to be higher (P: = 0.059) in subjects without lactose malabsorption after fresh yogurt consumption than after heated yogurt consumption. There were no significant changes in plasma acetate. In subjects with lactose malabsorption, 15 d of fresh yogurt consumption also increased propionate production compared with values at baseline (P: < 0.04). In the same group, the production of breath hydrogen was lower after fresh yogurt consumption than after heated yogurt consumption (P: < 0.01). CONCLUSIONS: In men with lactose malabsorption, chronic consumption of yogurt containing live bacterial cultures ameliorated the malabsorption, as evidenced by lower breath-hydrogen excretion, but increased propionate concentrations. In subjects without lactose malabsorption, such yogurt tended to increase propionate and increased butyrate.

Adult↗

High prevalence of lactose absorbers in Northern Sardinian patients with type 1 and type 2 diabetes mellitus.

BACKGROUND: Increased intestinal lactase activity has been shown to occur in alloxan and streptozotocin diabetic rats. OBJECTIVE: The objective of this study was to determine whether increased intestinal lactase activity is present in humans with diabetes mellitus. DESIGN: We assessed the capacity to digest lactose by measuring breath-hydrogen production after oral administration of lactose in 50 patients with type 1 diabetes, 50 patients with type 2 diabetes, and 50 healthy control subjects from Sassari, Sardinia, Italy, a population characterized by a low prevalence of lactase persistence (lactose absorbers). RESULTS: Fourteen percent of control subjects were lactose absorbers, compared with 48% of patients with type 1 diabetes and 52% of patients with type 2 diabetes (P < 0.005). The odds ratio of lactase persistence in patients with type 1 diabetes was 5.3 (95% CI: 2.0, 14.0) and in patients with type 2 diabetes was 5.5 (95% CI: 2.1, 14.5). CONCLUSIONS: Diabetes is associated with increased intestinal lactase activity in humans. Consequently, there is a greater exposure to glucose and galactose in diabetic patients with high lactose consumption. This may explain the association between diabetes and the risk of cataract.

Adult↗

Clinical applications of probiotic agents.

In the past century the beneficial roles of nonpathogenic bacteria in the intestinal lumen were described. In the past decade there has been a dramatic increase in scientific work supporting the concept that there are clinical benefits to ingesting specific nonpathogenic organisms (probiotics). The potential benefits of modifying the intestinal flora composition of certain high-risk groups, eg, premature infants, travelers, and children receiving antibiotics, are emerging in the literature. Studies documenting prophylactic and therapeutic benefits in acute viral gastroenteritis and in atopic disease point not only to the potential applications, but also to the fact that the mechanisms of action of these agents may be due to their interaction with the gut as an immunologic organ. The benefits documented thus far are of varying degree and are most likely dependent on the number of agents, the dose, the dosing patterns, and the characteristics of the host and its underlying luminal microbial environment. Consequently, the safety and specification of a particular probiotic agent and methods of delivery to a particular population for a particular purpose should be carefully documented before making broad recommendations. The cost-benefit assessment of adding probiotics to our diet for prophylactic or therapeutic purposes, as well as better regulation of these agents as commercial products, is also needed.

Child↗

Cow milk is not responsible for most gastrointestinal immune-like syndromes--evidence from a population-based study.

BACKGROUND: Gastrointestinal hypersensitivity to cow milk (CM) may be more common among school-aged children and young adults than previously thought. OBJECTIVE: The objective was to study various gastrointestinal complaints and the immunologic mechanisms associated with food-related, especially CM-related, gastrointestinal disorders in young adults. DESIGN: Of 827 subjects aged 16-21 y who completed a questionnaire on food-related gastrointestinal symptoms, 49 symptomatic subjects agreed to a clinical examination, including an interview, blood tests, a lactose-maldigestion test, a blinded CM challenge and, in severely symptomatic subjects (n = 12), an endoscopic examination. Twenty-nine subjects served as controls. RESULTS: Approximately 10% of the subjects reported having major gastrointestinal symptoms, mainly food-related (n = 70 of 86), during the preceding year. Specific organic disease was found in 2 symptomatic subjects: 1 case of celiac disease and 1 of colitis. The result of the lactose-maldigestion test was positive in 16 of the remaining 47 symptomatic subjects, but only 4 carried the C/C(-13910) genotype for adult-type hypolactasia. The symptomatic subjects had restricted their consumption of certain foods, particularly CM. However, in a blinded challenge, CM-induced symptoms were rare. The symptomatic subjects had higher plasma soluble intercellular adhesion molecule 1 (P = 0.007) and lower granzyme A (P = 0.001) concentrations than did the control subjects. Duodenal biopsy samples tended to have higher intraepithelial CD3(+) cell counts (P = 0.065) and a higher expression of transforming growth factor beta (P = 0.073) and interleukin 12p35 messenger RNA (P = 0.075) than did the control subjects. CONCLUSIONS: In an unselected cohort of young adults, 8% reported food-related gastrointestinal symptoms. The finding of immunologic activity implied the existence of a food-related gastrointestinal syndrome but not one induced by CM.

Abdominal Pain↗

The lactase persistence/non-persistence polymorphism is controlled by a cis-acting element.

Lactase activity is present at high levels in the small intestine of some human adults and not others. This is due to a genetically determined polymorphism which affects the developmental regulation of the expression of the lactase gene. This polymorphism is of considerable interest in relation to cultural differences in nutrition but despite exhaustive studies, the molecular basis has not yet been found. It has not even been shown whether the sequence differences reside within or adjacent to the lactase gene itself or in a trans-acting factor. We have therefore exploited known DNA 'marker' polymorphisms within the exons of the lactase gene to examine the expression of the individual lactase mRNA transcripts from persistent and non-persistent individuals in order to determine whether the regulation is in cis or trans. Our results show that in certain lactase persistent individuals one allele of the lactase gene is expressed at much lower levels than the other and these individuals tend to have intermediate lactase activities. It is proposed that these people are heterozygous for the lactase persistence and non-persistence alleles and that this means that the nucleotide substitutions responsible for the lactase persistence/non-persistence polymorphism are cis-acting. This narrows down considerably the area of the genome that needs to be searched for the relevant sequence differences.

Adult↗

Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element.

Lactase persistence is a heritable, autosomal dominant, condition that results in a sustained ability to digest the milk sugar lactose throughout adulthood. The majority of the world's human population experiences a decline in production of the digestive enzyme lactase-phlorizin hydrolase during maturation. However, individuals with lactase persistence continue to express high levels of the lactase gene into adulthood. Lactase persistence has been strongly correlated with single nucleotide genetic variants, C/T_(13910) and G/A_(22018), located 13.9 and 22 kb upstream from the lactase structural gene. We aimed to characterize a functional role for the polymorphisms in regulating lactase gene transcription. DNA in the region of the C/T_(13910) or G/A_(22018) human lactase variants was cloned upstream of the 3.0 kb rat lactase gene promoter in a luciferase reporter construct. Human intestinal Caco-2 cells were transfected with the lactase variant/promoter-reporter constructs and assayed for promoter activity. A 200 bp region surrounding the C_(13910) variant, associated with lactase non-persistence, results in a 2.2-fold increase in lactase promoter activity. The T_(13910) variant, associated with lactase persistence, results in an even greater 2.8-fold increase. The DNA sequence of the C/T_(13910) variants differentially interacts with intestinal cell nuclear proteins on EMSAs. AP2 co-transfection results in a similar repression of the C/T_(13910) variant/promoter-reporter constructs. The DNA region of the C/T_(13910) lactase persistence/non-persistence variant functions in vitro as a cis element capable of enhancing differential transcriptional activation of the lactase promoter. Such differential regulation by the C and T variants is consistent with a causative role in the mechanism specifying the lactase persistence/non-persistence phenotypes in humans.

Base Sequence↗

Major colorectal cancer aetiological hypotheses do not explain mortality trends among Maori and non-Maori New Zealanders.

New Zealand colorectal cancer mortality rates are presented for the period 1947-1980. Mortality has been increasing and is now the highest in the world for both males and females in the age range 35-64; indeed New Zealand mortality rates for those aged 35-44 are approximately twice those of other countries with high mortality. By contrast, colorectal cancer mortality rates among Maoris, the indigenous New Zealanders of Polynesian descent, have been decreasing so that they are now less than half the non-Maori mortality rates. These findings cannot be explained by ethnic differences in consumption of the major proposed dietary risk factors: total fat, cholesterol, meat, fibre and beer. Possible differences in the prevalence of lactose malabsorption, in faecal mutagen activity, and in the prevalence of colorectal polyps warrant further investigation.

Adult↗

Hypothesis is lactose a dietary risk factor for ischaemic heart disease?

The prevalence of primary adult lactose malabsorption (LM) in 23 ethnic groups was matched with national data on milk consumption and mortality rates from ischaemic heart disease (IHD). In 6 other ethnic groups prevalence of LM was related to unquantified assessments of milk consumption and frequency of IHD. On the available data, populations with a prevalence of LM over 30%, and whose consumption of milk is low or is largely in low lactose form, have a lower risk of IHD mortality than populations with a prevalence of LM under 30% and a high milk consumption. There is evidence against attributing these findings to genetic linkage between susceptibility to IHD mortality and persistent lactose absorption, or to differences in socio-economic development, cigarette consumption or intake of animal fats. The findings are compatible with an hypothesis that, if the correlation reported previously between milk consumption and IHD mortality is causal, lactose could be the responsible dietary factor.

Animals↗

Disturbed galactose metabolism in elderly and diabetic humans is associated with cataract formation.

Lactose consumption has been associated with a high incidence of cataract in northern Indian and southern Italian populations. Galactose absorbed after hydrolysis of lactose from milk in individuals with normal lactase activity is considered responsible. However, lactase-deficient subjects who often avoid drinking milk are able to digest lactose and absorb free galactose in fermented milk and yogurt. This study was conducted to evaluate the relationships between milk and yogurt consumption, galactose metabolism and cataract risk. Milk ingestion was dose-related with cataract risk in lactose digesters (particularly in diabetics) but not in lactose maldigesters. Conversely, yogurt intake had a protective dose-effect on cataract formation for the whole population. Maximal galactose concentrations after an oral galactose test increased exponentially with age. Red blood cell galactokinase activity was significantly lower in elderly subjects (> 60 y) than in young individuals (P < 0.05), and galactose-1-phosphate uridyl-transferase activity was significantly lower in institutionalized subjects and in home-living elderly with cataract than in healthy elderly subjects (P < 0.05). We conclude that the cataractogenic action of milk lactose is dependent on the disturbance of galactose metabolism in elderly subjects and that yogurt is not cataractogenic, although the mechanism of the protective effect of yogurt remains unknown.

Adult↗

Lactose absorption in patients with ovarian cancer.

To determine whether lactase persistence might be related to ovarian cancer risk, in 1994-1995 the authors assessed the capacity to digest lactose by measuring breath hydrogen production after oral administration of lactose in 50 women with ovarian cancer and 100 healthy controls. All of the women came from Sassari (Sardinia), Italy, an area where the population has a high frequency of lactose malabsorption. Thirty percent of cases were lactose absorbers, as compared with 15% of controls. The odds ratio for ovarian cancer among lactose absorbers was 2.51 (95% confidence interval 1.10-5.68). These results provide some support for a role of lactose ingestion and galactose cytotoxicity in the pathogenesis of ovarian cancer.

Administration, Oral↗

Adult hypolactasia, milk consumption, and age-specific fertility.

Beta-galactosidase (lactase) allows the digestion of lactose as its component sugars, galactose and glucose. Considerable variation exists worldwide in the prevalence of adults who lose the ability to digest lactose after infancy (hypolactasia) as well as in the amount of milk products they consume. Clearly, those populations in which hypolactasia is infrequent and milk consumption high will have greater dietary exposure to galactose. Because there is clinical and experimental evidence that galactose may be toxic to ovarian germ cells, the authors sought to determine whether age-specific fertility rates in various countries correlate with the prevalence of adult hypolactasia and per capita milk consumption by analysis of published data on these variables. The authors found significant correlations among these variables such that fertility at older ages is lower and the decline in fertility with aging is steeper in populations with high per capita consumption of milk and greater ability to digest its lactose component. These demographic data add to existing evidence that dietary galactose may deleteriously affect ovarian function.

Adolescent↗