Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Communication
  • Published:

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−13 910 meaning adult-type hypolactasia (primary LM) and the genotypes CT−13 910 and TT−13 910 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−13 910 genotype. Calcium intake from dairy products (P=0.10) and BMD, adjusted for age, weight, height, exercise, smoking, and estrogen use (P=0.71) were similar for the genotypes. Women with self-reported LI had reduced calcium intake from dairy products (P<0.0001) but they were more frequent users of calcium supplements than lactose-tolerants (P<0.0001). Adjusted BMD was similar for lactose intolerant and tolerant women (P=0.60). Of 104 women with previous fracture in the population-based cohort, 13.5% had the CC−13 910 genotype, which did not differ from the prevalence of 19.3% among 347 women without fractures (P=0.29). The frequency of the CC−13 910 genotype (23.1%) for 52 women with established osteoporosis was similar as for 59 control women (15.3%) (P=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.

Sponsorhip:

Supported by the Research Funding from Helsinki University Central Hospital (Erityisvaltionosuus) and by the Miina Sillanpää Foundation, Helsinki, Finland.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  • Birge Jr SJ, Keutmann HT, Cuatrecasas P & Whedon GD (1967): Osteoporosis, intestinal lactase deficiency and low dietary calcium intake. N. Engl. J. Med. 276, 445–448.

    Article  CAS  PubMed  Google Scholar 

  • Black RE, Williams SM, Jones IE & Goulding A (2002): Children who avoid drinking cow milk have low dietary calcium intakes and poor bone health. Am. J. Clin. Nutr. 76, 675–680.

    Article  CAS  PubMed  Google Scholar 

  • Buning C, Schmidt H, Lochs H & Ockenga J (2004): Genetic components of lactose intolerance and community frequency. J. Bone Miner. Res. 19, 1746.

    Article  PubMed  Google Scholar 

  • Carroccio A, Montalto G, Cavera G, Notarbatolo A & The Lactase Deficiency Study Group (1998): Lactose intolerance and self-reported milk intolerance: relationship with lactose maldigestion and nutrient intake. J. Am. Coll. Nutr. 17, 631–636.

    Article  CAS  PubMed  Google Scholar 

  • Cochet B, Jung A, Griessen M, Bartholdi P, Schaller P & Donath A (1983): Effects of lactose on intestinal calcium absorption in normal and lactase-deficient subjects. Gastroenterology 84, 935–940.

    CAS  PubMed  Google Scholar 

  • Corazza GR, Benati G, Di Sario A, Tarozzi C, Strocchi A, Passeri M & Gasbarrini G (1995): Lactose intolerance and bone mass in postmenopausal Italian women. Br. J. Nutr. 73, 479–487.

    Article  CAS  PubMed  Google Scholar 

  • Dawson-Hughes B, Dallal GE, Krall EA, Sadowski L, Sahyoun N & Tannenbaum S (1990): A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N. Engl. J. Med. 323, 878–883.

    Article  CAS  PubMed  Google Scholar 

  • de Vrese M, Stegelmann A, Richter B, Fenselau S, Laue C & Schrezenmeir J (2001): Probiotics-compensation for lactase insufficiency. Am. J. Clin. Nutr. 73 (Suppl. 2), 421.

    Article  Google Scholar 

  • Debongnie JC, Newcomer AD, McGill DB & Phillips SF (1979): Absorption of nutrients in lactase deficiency. Dig. Dis. Sci. 24, 225–231.

    Article  CAS  PubMed  Google Scholar 

  • Delmas PD (2002): Treatment of osteoporosis. Lancet 359, 2018–2026.

    Article  CAS  PubMed  Google Scholar 

  • Di Stefano M, Veneto G, Malservisi S, Cecchetti L, Minguzzi L, Strocchi A & Corazza GR (2002): Lactose malabsorption and intolerance and peak bone mass. Gastroenterology 122, 1793–1799.

    Article  CAS  PubMed  Google Scholar 

  • Enattah N, Välimäki V-V, Välimäki MJ, Löyttyniemi E, Sahi T & Järvelä I (2004): Molecularly defined lactose malabsorption, peak bone mass and bone turnover rate in young Finnish men. Calcif. Tiss. Int. 75, 488–493.

    Article  CAS  Google Scholar 

  • Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L & Järvela I (2002): Identification of a variant associated with adult-type hypolactasia. Nat. Genet. 30, 233–237.

    Article  CAS  PubMed  Google Scholar 

  • Finkenstedt G, Skrabal F, Gasser RW & Braunsteiner H (1986): Lactose absorption, milk consumption, and fasting blood glucose concentrations in women with idiopathic osteoporosis. BMJ 292, 161–162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fordham JN, Chinn DJ & Kumar N (2000): Identification of women with reduced bone density at the lumbar spine and femoral neck using BMD at the os calcis. Osteporos. Int. 11, 797–802.

    Article  CAS  Google Scholar 

  • Goulding A, Taylor RW, Keil D, Gold E, Lewis-Barned NJ & Williams SM (1999): Lactose malabsorption and rate of bone loss in older women. Age Ageing 28, 175–180.

    Article  CAS  PubMed  Google Scholar 

  • Honkanen R, Kroger H, Alhava E, Turpeinen P, Tuppurainen M & Saarikoski S (1997): Lactose intolerance associated with fractures of weight-bearing bones in Finnish women aged 38-57 years. Bone 21, 473–477.

    Article  CAS  PubMed  Google Scholar 

  • Honkanen R, Pulkkinen P, Jarvinen R, Kroger H, Lindstedt K, Tuppurainen M & Uusitupa M (1996): Does lactose intolerance predispose to low bone density? A population-based study of perimenopausal Finnish women. Bone 19, 23–28.

    Article  CAS  PubMed  Google Scholar 

  • Kanis JA, Melton III LJ, Christiansen C, Johnston CC & Khaltaev N (1994): The diagnosis of osteoporosis. J. Bone. Miner. Res. 9, 1137–1141.

    Article  CAS  PubMed  Google Scholar 

  • Kuokkanen M, Enattah NS, Oksanen A, Savilahti E, Orpana A & Jarvela I (2003): Transcriptional regulation of the lactase-phlorizin hydrolase gene by polymorphisms associated with adult type hypolactasia. Gut 52, 647–652.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Messer M & Dahlqvist A (1966): A one-step ultramicro method for the assay of intestinal disaccharidases. Anal. Biochem. 14, 376–392.

    Article  CAS  PubMed  Google Scholar 

  • Miller PD, Siris ES, Barrett-Connor E, Faulkner KG, Wehren LE, Abbott TA, Chen Y-T, Berger ML, Santora AC & Sherwood LM (2002): Prediction of fracture risk in postmenopausal white women with peripheral bone densitometry: evidence from the national osteoporosis risk assessment. J. Bone Miner. Res. 17, 2222–2230.

    Article  PubMed  Google Scholar 

  • Obermayer-Pietsch BM, Bonelli CM, Walter DE, Kuhn RJ, Fahrleitner-Pammer A, Berghold A, Goessler W, Stepan V, Dobnig H, Leb G & Renner W (2004): Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures. J. Bone Miner. Res. 19, 42–47.

    Article  PubMed  Google Scholar 

  • Olds LC & Sibley E (2003): Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element. Hum. Mol. Genet. 12, 2333–2340.

    Article  CAS  PubMed  Google Scholar 

  • Sahi T, Isokoski M, Jussila J, Launiala K & Pyörälä K (1973): Recessive inheritance of adult-type lactose malabsorption. Lancet 2, 823–826.

    Article  CAS  PubMed  Google Scholar 

  • Saltzman JR, Russell RM, Golner B, Barakat S, Dallal GE & Goldin BR (1999): A randomized trial of Lactobacillus acidophilus BG2FO4 to treat lactose intolerance. Am. J. Clin. Nutr. 69, 140–146.

    Article  CAS  PubMed  Google Scholar 

  • Stallings VA, Oddleifson NW, Negrini BY, Zemel BS & Wellens R (1994): Bone mineral content and dietary calcium intake in children prescribed a low-lactose diet. J. Pediatr. Gastroenterol. Nutr. 18, 440–445.

    Article  CAS  PubMed  Google Scholar 

  • Suarez FL, Savaiano DA & Levitt MD (1995): A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance. N. Engl. J. Med. 333, 1–4.

    Article  CAS  PubMed  Google Scholar 

  • Syvänen AC, Sajantila A & Lukka M (1993): Identification of individuals by analysis of biallelic DNA markers, using PCR and solid-phase minisequencing. Am. J. Hum. Genet. 52, 46–59.

    PubMed  PubMed Central  Google Scholar 

  • Tamm A (1994): Management of lactose intolerance. Scand. J. Gastroenterol. 202 (Suppl 1), 55–63.

    Article  CAS  Google Scholar 

  • Tremaine WJ, Newcomer AD, Riggs BL & McGill DB (1986): Calcium absorption from milk in lactase-deficient and lactase-sufficient adults. Dig. Dis. Sci. 31, 376–378.

    Article  CAS  PubMed  Google Scholar 

  • Wheadon M, Goulding A, Barbezat GO & Campbell AJ (1991): Lactose malabsorption and calcium intake as risk factors for osteoporosis in elderly New Zealand women. NZ Med. J. 104, 417–419.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M J Välimäki.

Additional information

Guarantor: MJ Välimäki.

Contributors: All investigators contributed to the study design and writing of the paper. NE performed the genotyping. TP performed medical examinations and was responsible for data collection. MJV is the guarantor and finalized the manuscript. EL was responsible for statistical analyses. IJ was responsible for the DNA analyses and supervised the lab work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Enattah, N., Pekkarinen, T., Välimäki, M. et al. Genetically defined adult-type hypolactasia and self-reported lactose intolerance as risk factors of osteoporosis in Finnish postmenopausal women. Eur J Clin Nutr 59, 1105–1111 (2005). https://doi.org/10.1038/sj.ejcn.1602219

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1602219

Keywords

This article is cited by

Search

Quick links