Lee Hooper and Asmaa Abdelhamid: The role of nutrition in disease prevention—how we can find better answers?

PUFAH Review team members from left to right standing: Lee Hooper, Xia Wang, Julii Brainard, Asmaa Abdelhamid, Oluseyi Florence Jimoh, Priti Biswas, Tracey Brown, Fujian Song. Katherine Deane (front row, sitting).

How can we get more information from dietary trials? It’s simple really. Often dietary interventions are trialled against a wide range of health outcomes—so there may be two trials assessing the effects of your intervention on cancers, three on cardiovascular disease, one on diabetes diagnosis, two on asthma, and two on cognition. This means that we have limited power to assess the effects of the nutritional intervention on diabetes, for example, because we only have a single trial looking at that specific outcome. Yet what if we asked each of the other nine trials whether any participants were diagnosed with diabetes during the trial? This will provide formally randomised data on diabetes diagnosis. You might find that some trialists won’t reply or did not collect diabetes diagnoses, but you may end up with five or six randomised trials of your intervention with diabetes data. Now you are in a much stronger position to assess whether your intervention increases or decreases the risk of developing diabetes.  

We had been thinking about this idea for a while and so were excited (and slightly daunted) when WHO Nutrition Guidance Expert Advisory Group asked us to assess the health effects of omega-3, omega-6, and total polyunsaturated fats on a broad swathe of health outcomes including mortality, CVD, body weight, lipids, diabetes, cognition, depression, cancers, and inflammatory bowel disease. [1,2,3,4,5,6,7,8] This gave us the opportunity to collect and examine the full set of long term randomised controlled trials of polyunsaturated interventions (regardless of primary outcome), and spend time amassing published, unpublished, and inaccessible health outcome data from these trials.

Preventative trials are essential to inform high quality lifestyle advice, keeping us all healthy for longer, but by their nature they have to involve a lot of participants and run for a long time to clock up enough events to be informative—consequently, they’re expensive. Observational data is complementary, with its strengths of having a large number of participants and a long duration, but it also has serious potential lifestyle confounding that we can never be quite sure has been factored out. Better use of trial outcome data may help us to amass greater quantities of useful randomised outcome data relatively cheaply, which would be a win-win. 

Carrying out this broad set of reviews has other advantages too. The additional contact with authors can improve the quality of our data (since author contact improves our understanding of methodological issues, as well as growing the dataset). Furthermore, as trials are used across a range of outcomes, it reduces the effort spent on each outcome (as searching, inclusion, data extraction, and assessment of risk of bias can be carried out in common across the reviews).  

So does this approach work? We think so. We present to you the results of our assessment of the effects of increasing long chain omega-3, alpha-linolenic acid, omega-6, and total polyunsaturated fats on diabetes diagnosis and glucose metabolism. [5] This is a much larger set of trials than used in comparable systematic reviews, where trials were not informative, and has indeed provided the power to assess the effects of omega-3 fats on diabetes diagnoses.This approach also appears to work for other outcomes, such as mortality, cardiovascular disease, cancers, depression, and cognition. [1,2,3,4,5,6,7] The dataset we used of all longer trials (regardless of primary outcomes) is published and available for others to use so they can assess further health outcomes. [9,10] The dataset is not perfect—we didn’t manage to contact all trial authors—but it is a good start, and it’s ready for others to build on. In the future, we need to improve on the ways we collect and enable access to these precious data from all conducted trials. Perhaps by using trials databases more fully, we can start to do this.

With excellent support from many trialists and a talented review team, this study has been fascinating to work on. We hope that our research will support further improvements in the methods researchers use to carry out systematic reviews of nutritional interventions.

 

Lee Hooper is a Reader in Research Synthesis, Nutrition & Hydration in the Norwich Medical School at the University of East Anglia. 

 

 

 

 

Asmaa Abdelhamid is an honorary research fellow at Norwich medical school, University of East Anglia 

Competing Interests: See research paper

 

 

References:

[1] Abdelhamid AS, Brown TJ, Brainard JS, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2018;11:CD003177. doi: DOI: 10.1002/14651858.CD003177.pub4

[2] Abdelhamid AS, Martin N, Bridges C, et al. Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2018;11:CD012345. doi: DOI: 10.1002/14651858.CD012345.pub3

[3] Hooper L, Al-Khudairy L, Abdelhamid AS, et al. Omega-6 fats for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2018;11:CD011094. doi: DOI: 10.1002/14651858.CD011094.pub4

[4] Brainard J, Jimoh OF, Deane K, et al. Omega-3, omega-6 and total polyunsaturated fat for cognition and dementia: Systematic review and meta-analysis of RCTs. submitted 2019

[5] Brown TJ, Brainard JS, Song F, et al. Omega-3, omega-6 and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: systematic review and meta-analysis of randomised controlled trials. Br Med J 2019;accepted

[6] Deane KHO, Jimoh OF, Biswas P, et al. Omega-3, omega-6 and total polyunsaturated fat for prevention of depression and anxiety symptoms: a systematic review and meta-analysis of randomised trials. submitted 2019

[7] Hanson S, Thorpe G, Winstanley L, et al. Omega-3, omega-6 and total dietary polyunsaturated fat on cancer incidence: systematic review and meta-analysis of randomised trials. submitted 2019

[8] Thorpe G, Ajabnoor S, Ahmed Z, et al. Dietary polyunsaturated fat for prevention and treatment of inflammatory bowel disease. PROSPERO 2017:CRD42017068704.

[9] Hooper L, Abdelhamid A, Brainard J, et al. Creation of a database to assess effects of omega-3, omega-6 and total polyunsaturated fats on health: database and methodology for a set of reviews. BMJ Open 2019;9(5):e029554. doi: DOI: 10.1136/bmjopen-2019-029554

[10] Abdelhamid A, Hooper L, Sivakaran R, et al. The Relationship Between Omega-3, Omega-6 and Total Polyunsaturated Fat and Musculoskeletal Health and Functional Status in Adults: A Systematic Review and Meta-analysis of RCTs. Calcified Tissue International 2019 doi: DOI: 10.1007/s00223-019-00584-3