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Associations of fat and carbohydrate intake with cardiovascular disease and mortality: prospective cohort study of UK Biobank participants

BMJ 2020; 368 doi: (Published 18 March 2020) Cite this as: BMJ 2020;368:m688
  1. Frederick K Ho, research associate1,
  2. Stuart R Gray, senior lecturer2,
  3. Paul Welsh, senior lecturer2,
  4. Fanny Petermann-Rocha, PhD student12,
  5. Hamish Foster, clinical academic GP fellow1,
  6. Heather Waddell, PhD student2,
  7. Jana Anderson, research fellow1,
  8. Donald Lyall, lecturer1,
  9. Naveed Sattar, professor2,
  10. Jason M R Gill, professor2,
  11. John C Mathers, professor3,
  12. Jill P Pell, professor1,
  13. Carlos Celis-Morales, research fellow1245
  1. 1Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
  2. 2Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK
  3. 3Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
  4. 4Center for Exercise Physiology Research (CIFE), University Mayor, Santiago, Chile
  5. 5Research Group in Education, Physical Activity and Health (GEEAFyS), Universidad Católica del Maule, Talca, Chile
  1. Correspondence to: C Celis-Morales, BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK carlos.celis{at} (or @carloscelism on Twitter)
  • Accepted 14 February 2020


Objective To investigate the association of macronutrient intake with all cause mortality and cardiovascular disease (CVD), and the implications for dietary advice.

Design Prospective population based study.

Setting UK Biobank.

Participants 195 658 of the 502 536 participants in UK Biobank completed at least one dietary questionnaire and were included in the analyses. Diet was assessed using Oxford WebQ, a web based 24 hour recall questionnaire, and nutrient intakes were estimated using standard methodology. Cox proportional models with penalised cubic splines were used to study non-linear associations.

Main outcome measures All cause mortality and incidence of CVD.

Results 4780 (2.4%) participants died over a mean 10.6 (range 9.4-13.9) years of follow-up, and 948 (0.5%) and 9776 (5.0%) experienced fatal and non-fatal CVD events, respectively, over a mean 9.7 (range 8.5-13.0) years of follow-up. Non-linear associations were found for many macronutrients. Carbohydrate intake showed a non-linear association with mortality; no association at 20-50% of total energy intake but a positive association at 50-70% of energy intake (3.14 v 2.75 per 1000 person years, average hazard ratio 1.14, 95% confidence interval 1.03 to 1.28 (60-70% v 50% of energy)). A similar pattern was observed for sugar but not for starch or fibre. A higher intake of monounsaturated fat (2.94 v 3.50 per 1000 person years, average hazard ratio 0.58, 0.51 to 0.66 (20-25% v 5% of energy)) and lower intake of polyunsaturated fat (2.66 v 3.04 per 1000 person years, 0.78, 0.75 to 0.81 (5-7% v 12% of energy)) and saturated fat (2.66 v 3.59 per 1000 person years, 0.67, 0.62 to 0.73 (5-10% v 20% of energy)) were associated with a lower risk of mortality. A dietary risk matrix was developed to illustrate how dietary advice can be given based on current intake.

Conclusion Many associations between macronutrient intake and health outcomes are non-linear. Thus dietary advice could be tailored to current intake. Dietary guidelines on macronutrients (eg, carbohydrate) should also take account of differential associations of its components (eg, sugar and starch).


  • Contributors: FKH and SRG contributed equally to this work and are joint first authors. JCM, JPP, and CCM contributed equally to this work and are joint senior authors. FKH, SRG, JCM, JPP, and CCM designed the study. FKH, SRG, and CCM conducted the statistical analysis and wrote the first draft. SRG, PW, FPR, HF, HW, JA, DL, NS, JMRG, JCM, and JPP critically revised the manuscript. FKH, JPP and CCM are the guarantors of the manuscript and accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: UK Biobank was established by the Wellcome Trust, Medical Research Council, Department of Health, Scottish government, and Northwest Regional Development Agency. It has also had funding from the Welsh assembly government and the British Heart Foundation.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish government, and Northwest Regional Development Agency; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was performed under generic ethical approval obtained by UK Biobank from the National Health Service National Research Ethics Service (approval letter ref 11/NW/0382, 17 June 2011).

  • Data sharing: No additional data available.

  • The manuscript’s guarantors (JPP and CCM) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

  • Dissemination to participants and related patient and public communities: Results of the study will be linked in the UK Biobank website for research participants and relevant patient and public communities.

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