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Abstracts

Life Extension Magazine November 2013
Abstracts

Lactase

Lactose and milk intolerance: clinical implications.

We studied 166 hospitalized male patients to determine the clinical importance of tolerance-test-determined “lactose intolerance,” assumed to affect most of the world’s adults. Abnormal lactose tolerance tests were found in 81% of 98 blacks, 12% of 59 whites of Scandinavian or Northwestern European extraction, and three of nine non-European whites. Seventy-two per cent of the “lactose-intolerant” subjects had previously realized that milk drinking could induce abdominal and bowel symptoms. Two hundred and forty milliliters of low-fat milk produced gaseousness or cramps in 59% of 44 “lactose-intolerant” men, and 68% were symptomatic with the equivalent amount of lactose. None of 18 “lactose-tolerant” men noted symptoms with milk or lactose. Refusal to drink 240 ml of low-fat milk served with meals correlated significantly with “lactose-intolerance”: 31.4% versus 12.9% among “lactose-tolerant” patients. “Lactose intolerance” is common in adults and is a clinically relevant problem.

N Engl J Med. 1975 May 29;292(22):1156-9

Review article: lactose intolerane in clinical practice­—myths and realities.

BACKGROUND: Approximately 70% of the world population has hypolactasia, which often remains undiagnosed and has the potential to cause some morbidity. However, not everyone has lactose intolerance, as several nutritional and genetic factors influence tolerance. AIMS: To review current clinical practice and identify published literature on the management of lactose intolerance. METHODS: PubMed was searched using the terms lactose, lactase and diet to find original research and reviews. Relevant articles and clinical experience provided the basis for this review. RESULTS: Lactose is found only in mammalian milk and is hydrolysed by lactase in the small intestine. The lactase gene has recently been identified. ‘Wild-type’ is characterized by lactase nonpersistence, often leading to lactose intolerance. Two genetic polymorphisms responsible for persistence have been identified, with their distribution concentrated in north Europeans. Symptoms of lactose intolerance include abdominal pain, bloating, flatulence and diarrhoea. Diagnosis is most commonly by the lactose hydrogen breath test. However, most people with hypolactasia, if given appropriate advice, can tolerate some lactose-containing foods without symptoms. CONCLUSION: In clinical practice, some people with lactose intolerance can consume milk and dairy foods without developing symptoms, whereas others will need lactose restriction.

Aliment Pharmacol Ther. 2008 Jan 15;27(2):93-103

A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance.

BACKGROUND: Ingestion of a large dose of the milk sugar lactose--for example, the 50-g load in 1 liter of milk--causes symptoms such as abdominal pain, diarrhea, bloating, and flatulence in the majority of people with lactose malabsorption. It is uncertain whether the ingestion of more common doses of lactose, such as the amount in 240 ml (8 oz) of milk, causes symptoms. Some people insist that even smaller quantities of milk, such as the amount used with cereal or coffee, cause severe gastrointestinal distress. METHODS: In a randomized, double-blind, crossover trial, we evaluated gastrointestinal symptoms in 30 people (mean age, 29.4 years; range, 18 to 50) who reported severe lactose intolerance and said they consistently had symptoms after ingesting less than 240 ml of milk. The ability to digest lactose was assessed by measuring the subjects’ end-alveolar hydrogen concentration after they ingested 15 g of lactose in 250 ml of water. Subjects then received either 240 ml of lactose-hydrolyzed milk containing 2% fat or 240 ml of milk containing 2% fat and sweetened with aspartame to approximate the taste of lactose-hydrolyzed milk; each type of milk was administered daily with breakfast for a one-week period. Using a standardized scale, subjects rated the occurrence and severity of bloating, abdominal pain, diarrhea, and flatus and recorded each passage of flatus. RESULTS: Twenty-one participants were classified as having lactose malabsorption and nine as being able to absorb lactose. During the study periods, gastrointestinal symptoms were minimal (mean symptom-severity scores for bloating, abdominal pain, diarrhea, and flatus between 0.1 and 1.2 [1 indicated trivial symptoms; and 2, mild symptoms]). When the periods were compared, there were no statistically significant differences in the severity of these four gastrointestinal symptoms. For the lactose-malabsorption group, the mean (+/- SEM) difference in episodes of flatus per day was 2.5 +/- 1.1 (95% confidence interval, 0.2 to 4.8). Daily dietary records indicated a high degree of compliance, with no additional sources of lactose reported. CONCLUSIONS: People who identify themselves as severely lactose-intolerant may mistakenly attribute a variety of abdominal symptoms to lactose intolerance. When lactose intake is limited to the equivalent of 240 ml of milk or less a day, symptoms are likely to be negligible and the use of lactose-digestive aids unnecessary.

N Engl J Med. 1995 Jul 6;333(1):1-4

Management and treatment of lactose malabsorption.

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 beta-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.

World J Gastroenterol . 2006 Jan 14;12(2):187-91

Enzyme replacement therapy for primary adult lactase deficiency. Effective reduction of lactose malabsorption and milk intolerance by direct addition of beta-galactosidase to milk at mealtime.

The addition of microbial beta-galactosidases directly to milk at mealtime represents a potential “enzyme replacement therapy” for primary lactase deficiency. We used the hydrogen breath test as the index of incomplete carbohydrate absorption to assess the efficacy of two enzymes--one from yeast, Kluyveromyces lactis (LactAid), and the other from the fungus Aspergillus niger (Lactase N)--to assist in the hydrolysis of 18 g of lactose in 360 ml (12 oz) of whole milk when consumed by an adult lactose malabsorber. Graded amounts of Lactase N produced, at best, a 53% relative reduction in breath hydrogen excretion, whereas quantitative elimination of excess hydrogen excretion was produced by 1 and 1.5 g of LactAid. A double-blind, controlled, crossover trial was subsequently performed in 50 healthy, unselected Mexican adults, to whom 360 ml of cow’s milk was presented in the three forms in a randomized order: intact milk, prehydrolyzed milk, and milk to which 1 g of LactAid was added immediately before consumption. Among the 25 subjects with incomplete carbohydrate absorption with intact milk, adding enzyme 5-min before consumption produced a 62% reduction in breath hydrogen excretion, and symptoms of intolerance were significantly reduced. The feasibility of effective enzyme replacement therapy with a beta-galactosidase from K. lactis is demonstrated.

Gastroenterology. 1984 Nov;87(5):1072-82

Cow’s milk allergy versus cow milk intolerance.

BACKGROUND: Although cow’s milk allergy (CMA) and cow’s milk intolerance (CMI) are two different terms, they are often used interchangeably, resulting in confusion both in clinical practice and in research reports. OBJECTIVE: To promote the appropriate differential use of the terms CMA and CMI. METHODS: Highlighting the differences in clinical and laboratory findings between CMA and CMI. Information was derived from reviewing the literature on these two topics, supplemented by the clinical experience of the author. RESULTS: CMA is an immunologically mediated reaction to cow’s milk proteins that may involve the gastro-intestinal tract, skin, respiratory tract, or multiple systems, ie, systemic anaphylaxis. Its prevalence in the general population is probably 1 to 3%, being highest in infants and lowest in adults. Even though it can cause severe morbidity and even fatality, dietary elimination is associated with good prognosis. However, CMI should refer to nonimmunologic reactions to cow’s milk (CM), such as disorders of digestion, absorption, or metabolism of certain CM components. The most common cause of CMI is lactase deficiency, which is mostly acquired during late childhood or adulthood. It has high racial predilection, being highest in dark-skinned populations and lowest in northern Europeans. Lactose intolerance is generally a benign condition, with symptoms limited to the gastro-intestinal tract, yet the primary acquired type lasts for a lifetime. Symptoms can be well ameliorated by reducing the intake of CM or using lactose-hydrolyzing agents. CONCLUSIONS: Adverse reactions to CM should be differentiated into immunologic (CMA) and nonimmunologic (CMI). The latter is still a general term that comprises several conditions and requires further differentiation.

Ann Allergy Asthma Immunol. 2002 Dec;89(6 Suppl 1):56-60

Structural basis of specificity in tetrameric Kluyveromyces lactis b-galactosidase.

b-Galactosidase or lactase is a very important enzyme in the food industry, being that from the yeast Kluyveromyces lactis the most widely used. Here we report its three-dimensional structure both in the free state and complexed with the product galactose. The monomer folds into five domains in a pattern conserved with the prokaryote enzymes of the GH2 family, although two long insertions in domains 2 and 3 are unique and related to oligomerization and specificity. The tetrameric enzyme is a dimer of dimers, with higher dissociation energy for the dimers than for its assembly. Two active centers are located at the interface within each dimer in a narrow channel. The insertion at domain 3 protrudes into this channel and makes putative links with the aglycone moiety of docked lactose. In spite of common structural features related to function, the determinants of the reaction mechanism proposed for Escherichia coli b-galactosidase are not found in the active site of the K. lactis enzyme. This is the first X-ray crystal structure for a b-galactosidase used in food processing.

J Struct Biol. 2012 Feb;177(2):392-401

Dietary manipulation of postprandial colonic lactose fermentation: II. Addition of exogenous, microbial beta-galactosidases at mealtime.

The feasibility and efficacy of adding microbial beta-galactosidase enzymes directly to milk at the time of consumption was explored in adult lactose-malabsorbers. The hydrogen breath test, and on one occasion, the rise in blood glucose, were used as indices of the completeness of intraintestinal hydrolysis and absorption of milk lactose. When added to 360 ml of cow milk containing 18 g of lactose, empirical dosages of three beta-galactosidases--one from Kluyveromyces (yeast) and two from Aspergillus (fungal)--had some effectiveness in reducing postprandial H2 excretion, although no in vivo treatment at the dosages chosen was as effective as pre-incubation of the milk in vitro. The yeast enzyme also reduced symptom frequency as compared to intact milk and enhanced postprandial rises in blood glucose. The replacement therapy with exogenous, food-grade beta-galactosidases may provide a useful intervention to reduce lactose malabsorption and milk intolerance in individuals with primary lactase deficiency.

Am J Clin Nutr. 1985 Feb;41(2):209-21

The relationship between lactose tolerance test results and symptoms of lactose intolerance.

OBJECTIVE: A standard for the assessment of lactose malabsorption does not exist. As measured by lactose tolerance tests, insufficient increase in blood glucose or increased breath hydrogen (H2) excretion after lactose ingestion is regarded as pathological. In this study, we have tried to elucidate the relationship between lactose tolerance test results and symptoms after a lactose challenge. This relationship might be an indicator for the validity of the test. METHODS: In a prospective study, 309 consecutive patients with suspected lactose malabsorption underwent a lactose tolerance test. After consumption of 50 g of lactose, blood glucose and breath H2 concentrations were measured. During the test (240 min), the severity of bloating, flatulence, abdominal distention, and diarrhea were semiquantitatively scored as 0, 1, or 2. The individual sum of these four scores was calculated and denoted as the total symptom score (TSS). All subjects were classified according to their TSS to compare symptoms with peak breath-H2 concentration and change in blood glucose concentration, respectively. RESULTS: The glucose and breath H2 response were pathological in 51.1 and 39.5% of cases, respectively. A stepwise increase in TSS of 1 point was associated with a significant increase (p < 0.05) in mean peak H2 concentration. However, a significantly lower glucose increment compared with patients with a TSS of 0 was found only in patients with a TSS of 2 or 4. The mean symptom score differed significantly between the positive and negative breath tests (p < 0.001), but did not differ between the positive and negative glucose response results. CONCLUSIONS: This study shows that GI symptoms after a lactose challenge are strongly associated with the amount of H2 excretion. The relationship between the increase in glucose concentration and symptoms after a lactose load is less evident. Thus, the H2 breath test seems to be superior to the measurement of blood glucose increment as a diagnostic tool in lactose malabsorption, although the true predictive value of this test only can be determined after a period of dietary treatment.

Am J Gastroenterol. 1997 Jun;92(6):981-4

The genetically programmed down-regulation of lactase in children.

BACKGROUND & AIMS: Intestinal lactase activity is high in all healthy human babies, but in adults a genetic polymorphism, which acts in cis to the lactase gene, determines high or low messenger RNA (mRNA) expression and activity (lactase persistence and nonpersistence, respectively). Our aim was to investigate the onset of expression of this polymorphism in children. METHODS: Activities were analyzed in relation to age in normal biopsy specimens from a 20-year collection of diagnostic specimens. In a smaller set of 32 samples, aged 2-132 months, RNA was extracted for semiquantitative reverse-transcription polymerase chain reaction. Marker polymorphisms were used to determine the allelic origin of lactase mRNA transcripts. RESULTS: Analysis of 866 children showed evidence that the lactase persistence/nonpersistence polymorphism began before 5 years of age. The 32 children tested had high lactase mRNA and activity. Six children aged 2-16 months showed equal expression of two alleles, 2 children aged 7 and 14 months showed slightly asymmetric expression, and 7 children aged 22-132 months showed very asymmetric expression, the second allele being undetectable in the 11-year-old, as previously seen in lactase-persistent heterozygote adults. CONCLUSIONS: Genetically programmed down-regulation of the lactase gene is detectable in children from the second year of life, although the onset and extent are somewhat variable.

Gastroenterology. 1998 Jun;114(6):1230-6