Genetically defined adult-type hypolactasia and self-reported lactose intolerance as risk factors of osteoporosis in Finnish postmenopausal women

Abstract

Objective: To study the relationships of molecularly defined lactose malabsorption (LM) and self-reported lactose intolerance (LI) to bone mineral density (BMD) and fractures among Finnish postmenopausal women. Design: A cross-sectional study of two cohorts. Setting: Helsinki University Central Hospital. Subjects: One cohort was population-based and comprised 453 women, aged 62-78 (mean 69) y. Another comprised 52 women, aged 69-85 (mean 75) y, with osteoporotic fractures and 59 control women, aged 69-83 (mean 74) y, without osteoporosis. Methods: A single nucleotide polymorphism of the lactase (LCT) gene at chromosome 2q21-22 was studied. It shows complete association with intestinal disaccharidase activity, with the genotype CC À13 910 meaning adult-type hypolactasia (primary LM) and the genotypes CT À13 910 and TT À13 910 lactose absorption. BMD of the heel was measured by dual-energy X-ray absorptiometry (DXA). Results: In the population-based cohort, 16.0% of women had self-reported LI but only 15.3% of them had the CC À13 910 genotype. Calcium intake from dairy products (P ¼ 0.10) and BMD, adjusted for age, weight, height, exercise, smoking, and estrogen use (P ¼ 0.71) were similar for the genotypes. Women with self-reported LI had reduced calcium intake from dairy products (Po0.0001) but they were more frequent users of calcium supplements than lactose-tolerants (Po0.0001). Adjusted BMD was similar for lactose intolerant and tolerant women (P ¼ 0.60). Of 104 women with previous fracture in the populationbased cohort, 13.5% had the CC À13 910 genotype, which did not differ from the prevalence of 19.3% among 347 women without fractures (P ¼ 0.29). The frequency of the CC À13 910 genotype (23.1%) for 52 women with established osteoporosis was similar as for 59 control women (15.3%) (P ¼ 0.19). Conclusion: Molecularly defined LM and self-reported LI are not risk factors for osteoporosis, if calcium intake from diet and/or supplements remains sufficient. Our study confirms the poor correlation between self-reported LI and LM established by different techniques.

Correlation between lactose absorption and the C/T-13910 and G/A-22018 mutations of the lactase-phlorizin hydrolase (LCT) gene in adult-type hypolactasia

“…Additionally, a weak correlation between selfreported lactose tolerance and presence of the LCT mutation has been previously shown (14), also in a population of equal gender distribution (15).…”

Tolerance of different dairy products in subjects with symptomatic lactose malabsorption due to adult type hypolactasia

“…In the absence of guidelines for LI subjects, the common therapeutic approach involves the exclusion of milk and dairy products from the diet. An insufficient vitamin D and calcium intake can lead to poor health outcomes, particularly in relation to bone mineral density and the risk of fractures [15,16]. The determination of whether fermented dairy products can be better tolerated than milk may contribute to the development of evidence-based dietary recommendations that meet the needs of LI individuals.…”

Ingestão de cálcio e densidade mineral óssea em mulheres adultas intolerantes à lactose

“…Esses resultados estão de acordo com outros estudos que encontraram baixo consumo de cálcio para indivíduos com IL, com valores entre 400mg/dia -1 a 685mg/dia -1 para o grupo IL, e de 800mg/dia -1 a 905mg/dia -1 para o grupo-controle 9,12,13,19,27 . Entretanto, os valores de ingestão de cálcio em ambos os grupos (controle e intolerante) do presente estudo são consideravelmente menores do que os relatados na literatura 9,12,13,19,27 . Uma possível explicação para essa variação do baixo consumo de cálcio por indivíduos adultos saudá- veis seria uma possível diferença cultural e de hábitos alimentares das mulheres do presente estudo em relação às recrutadas em outros estudos na literatura.…”

“…Realmente, alguns estudos sugerem consumo inadequado e abaixo do recomendado de cálcio em algumas populações 15,12,27 . Contudo, as diferenças no consumo de cálcio entre indivíduos com IL e controle relatados na literatura 9,12,13,19,27 é de aproximadamente 285mg/dia -1 a 400mg/dia -1 , muito similar à diferença encontrada no presente estudo (~400mg/dia -1 ).…”

“…Assim, apesar da possibilidade de existir outros fatores que poderiam afetar a DMO, tem-se o reduzido consumo de cálcio no GIL -muito abaixo dos 1.000mg/dia -1 recomendados 29 -, um dos fatores determinantes para esse quadro. A baixa ingestão de cálcio se deve, provavelmente, a uma baixa ingestão de leite, queijo, iogurte e outros derivados em mulheres IL, conforme descrito na literatura 15,17,27,28 . Assim, devido ao baixo consumo de leite e derivados, é esperado que exista um balanço negativo de cálcio e que se instale um quadro de fragilidade óssea compatível com osteopenia/osteoporose.…”