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Lactase persistence, milk intake, and mortality in the Danish general population: a Mendelian randomization study

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Abstract

Meta-analyses have suggested no association between milk intake and mortality. Since only few studies have been conducted, we investigated the association between the lactase persistent genetic variant LCT-13910 C/T (rs4988235), a proxy for long-term low and high intake of milk, and mortality. We used two Danish population-based studies with self-reported intake of milk and genotyping for LCT-13910 C/T. We obtained information on all-cause and cause-specific mortality (cardiovascular and cancer) from the national Danish registries. We used multivariable adjusted Cox regression to assess the association between milk intake and mortality in 74,241 individuals, and both logistic and Cox-regression to assess the association between genetic lactase persistence and mortality in 82,964 individuals using a Mendelian randomization design. We applied per T-allele, co-dominant and dominant models. During a mean follow-up of 7 years, 9759 individuals died, 2166 from cardiovascular disease, and 2822 from cancer. Observationally, there was no association between intake of skimmed milk and all-cause or cardiovascular mortality, and we did not find any associations between intake of semi-skimmed or whole milk with all-cause or cause-specific mortality. Intake of skimmed milk was associated with lower cancer mortality with a hazard ratio of 0.97 (95% CI 0.96–1.00) per doubling in milk intake. Per T-allele, milk intake increased with 0.58 (0.50–0.68) glasses/week. Genetically, we found no associations between the lactase persistent LCT-13910 C/T genotype and all-cause or cause-specific mortality; per T-allele OR (95% CI) for all-cause mortality was 1.02 (0.97–1.06). Our study did not provide strong evidence of observational or genetic associations between milk intake and all-cause or cause-specific mortality.

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Acknowledgements

We are grateful to all participants and staff in the Copenhagen General Population Study and the Copenhagen City Heart Study for their valuable contributions.

Funding

The Copenhagen General Population Study was funded by The Danish Council for Independent Research; Medical Sciences(FSS); Herlev and Gentofte Hospital, Copenhagen University Hospital; Copenhagen County Foundation; and Chief Physician Johan Boserup and Lise Boserup’s Fund, Denmark. The Copenhagen City Heart Study was funded by the Danish Heart Foundation. HKMB’s PhD project was partly funded by the Danish Dairy Research Foundation; the Research Unit at Naestved Hospital, Denmark; and the Regional Research Unit in Region Zealand, Denmark. None of the funding sources were involved in the design, conduct of study, collection, management, analysis, or interpretation of data, or in preparation of the manuscript, and were not involved in the decision to submit the manuscript.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Naestved Hospital, Naestved, Denmark

    Helle Kirstine Mørup Bergholdt

  2. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Helle Kirstine Mørup Bergholdt, Børge Grønne Nordestgaard, Anette Varbo & Christina Ellervik

  3. Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark

    Børge Grønne Nordestgaard & Anette Varbo

  4. The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark

    Børge Grønne Nordestgaard

  5. Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark

    Christina Ellervik

  6. Department of Laboratory Medicine, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA

    Christina Ellervik

Authors
  1. Helle Kirstine Mørup Bergholdt
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  2. Børge Grønne Nordestgaard
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  3. Anette Varbo
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  4. Christina Ellervik
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Contributions

Authors responsible for this article are Helle KM Bergholdt(HKMB), Børge G Nordestgaard(BGN), Anette Varbo(AV) and Christina Ellervik(CE). BGN and CE conceived and designed the research and acquired the data. Literature search was performed by HKMB. HKMB prepared the data, performed statistical analyses, and drafted the manuscript. All authors undertook critical revisions of the manuscript and contributed intellectually to the development of this paper, as well as performed final approval of the paper. All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data in the analyses, and affirm that the manuscript is an honest, accurate, and transparent account of the study being reported and that no important aspects of the study have been omitted.

Corresponding author

Correspondence to Christina Ellervik.

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Conflicts of interest

All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author). Dr Bergholdt reports grant from the Danish Dairy Research Foundation during the conduct of the study. Dr Nordestgaard, Dr Varbo, and Dr Ellervik report no conflicts of interest.

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Bergholdt, H.K.M., Nordestgaard, B.G., Varbo, A. et al. Lactase persistence, milk intake, and mortality in the Danish general population: a Mendelian randomization study. Eur J Epidemiol 33, 171–181 (2018). https://doi.org/10.1007/s10654-017-0328-x

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  • DOI: https://doi.org/10.1007/s10654-017-0328-x

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