Ioannidis has stated that the field of nutritional epidemiology has generated confusion and numerous implausible findings and is in need of radical reform. One of the reforms he proposes is to conduct analyses that take into account the "totality for all nutritional factors measured". This approach is based on isolating and reducing diet into numerous independent variables with little regard to prior knowledge or the interrelations among dietary components, and relying on a "discovery" approach. This method, akin to genomewide association studies (GWAS), would involve very large sample sizes, small associations, no prior knowledge, and multiple testing considerations. This method is contrary to the more traditional hypothesis generating and testing approach built on all types of evidence. This commentary will contrast how suitable these two approaches are to study diet and disease.
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Trepanowski JF, Ioannidis JPA. Perspective: limiting dependence on nonrandomized studies and improving randomized trials in human nutrition research: why and how. Adv Nutr. 2018;9(4):367–77.
Ioannidis JP. Implausible results in human nutrition research. BMJ. 2013;347:f6698.
Ioannidis JPA. The challenge of reforming nutritional epidemiologic research. JAMA. 2018;320(10):969–70.
Satija A, et al. Perspective: are large, simple trials the solution for nutrition research? Adv Nutr. 2018;9(4):378–87.
Patel CJ, et al. Systematic evaluation of environmental and behavioural factors associated with all-cause mortality in the United States national health and nutrition examination survey. Int J Epidemiol. 2013;42(6):1795–810.
Eaton SB, Konner M. Paleolithic nutrition. N Engl J Med. 1985;312:283–9.
Konner M, Eaton SB. Paleolithic nutrition: twenty-five years later. Nutr Clin Pract. 2010;25(6):594–602.
Willett WC. Dietary fats and coronary heart disease. J Intern Med. 2012;272(1):13–24.
GBD 2016 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1345–422.
Satija A, et al. Understanding nutritional epidemiology and its role in policy. Adv Nutr. 2015;6(1):5–18.
Yuan C, et al. Relative validity of nutrient intakes assessed by questionnaire, 24-hour recalls, and diet records as compared with urinary recovery and plasma concentration biomarkers: findings for women. Am J Epidemiol. 2018;187(5):1051–63.
Schwingshackl L, et al. Food groups and risk of all-cause mortality: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr. 2017;105(6):1462–73.
Filippini T, et al. The effect of potassium supplementation on blood pressure in hypertensive subjects: a systematic review and meta-analysis. Int J Cardiol. 2017;230:127–35.
Gay HC, et al. Effects of different dietary interventions on blood pressure: systematic review and meta-analysis of randomized controlled trials. Hypertension. 2016;67(4):733–9.
Binia A, et al. Daily potassium intake and sodium-to-potassium ratio in the reduction of blood pressure: a meta-analysis of randomized controlled trials. J Hypertens. 2015;33(8):1509–20.
Perez V, Chang ET. Sodium-to-potassium ratio and blood pressure, hypertension, and related factors. Adv Nutr. 2014;5(6):712–41.
Appel LJ. The effects of dietary factors on blood pressure. Cardiol Clin. 2017;35(2):197–212.
Aune D, et al. Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality—a systematic review and dose-response meta-analysis of prospective studies. Int J Epidemiol. 2017;46(3):1029–56.
Aune D, et al. Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies. BMJ. 2016;353:i2716.
Sacks FM, et al. Dietary fats and cardiovascular disease: a presidential advisory from the American Heart Association. Circulation. 2017;136(3):e1–23.
Hooper L, et al. Reduction in saturated fat intake for cardiovascular disease. Cochrane Database Syst Rev. 2015;(6). p. CD011737.
Estruch R, et al. Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med. 2018;378(25):e34.
Aune D, et al. Nut consumption and risk of cardiovascular disease, total cancer, all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis of prospective studies. BMC Med. 2016;14(1):207.
Jakobsen MU, et al. Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies. Am J Clin Nutr. 2009;89(5):1425–32.
Estruch R, et al. Retraction and republication: primary prevention of cardiovascular disease with a mediterranean diet. N Engl J Med. 2018;378(25):2441–2.
Howard BV, et al. Low-fat dietary pattern and risk of cardiovascular disease: the Women’s Health Initiative randomized controlled dietary modification trial. JAMA. 2006;295(6):655–66.
de Lorgeril M, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet. 1994;343(8911):1454–9.
Giovannucci E. A framework to understand diet, physical activity, body weight, and cancer risk. Cancer Causes Control. 2018;29(1):1–6.
Fogelholm M, et al. Dietary macronutrients and food consumption as determinants of long-term weight change in adult populations: a systematic literature review. Food Nutr Res. 2012;56:19103.
Swinburn BA, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011;378(9793):804–14.
Rodgers A, et al. Prevalence trends tell us what did not precipitate the US obesity epidemic. Lancet Public Health. 2018;3(4):e162–3.
Scarborough P, et al. Increased energy intake entirely accounts for increase in body weight in women but not in men in the UK between 1986 and 2000. Br J Nutr. 2011;105(9):1399–404.
Young LR, Nestle M. Expanding portion sizes in the US marketplace: implications for nutrition counseling. J Am Diet Assoc. 2003;103(2):231–4.
Bray GA, Nielsen SJ, Popkin BM. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr. 2004;79(4):537–43.
Giovannucci E. An integrative approach for deciphering the causal associations of physical activity and cancer risk: the role of adiposity. J Natl Cancer Inst. 2018;110(9):935–41.
Tabung FK, et al. Development and validation of an empirical dietary inflammatory index. J Nutr. 2016;146(8):1560–70.
Tabung FK, et al. Development and validation of empirical indices to assess the insulinaemic potential of diet and lifestyle. Br J Nutr. 2016;8:1–12.
Tabung FK, et al. Association of dietary inflammatory potential with colorectal cancer risk in men and women. JAMA Oncol. 2018;4(3):366–73.
Tabung FK, et al. Association of dietary insulinemic potential and colorectal cancer risk in men and women. Am J Clin Nutr. 2018;108(2):363–70.
Toivonen KI, et al. Folic acid supplementation during the preconception period: a systematic review and meta-analysis. Prev Med. 2018;114:1–17.
He K, et al. Folate, vitamin B6, and B12 intakes in relation to risk of stroke among men. Stroke. 2004;35(1):169–74.
Bazzano LA, et al. Dietary intake of folate and risk of stroke in US men and women: NHANES I epidemiologic follow-up study. National Health and Nutrition Examination Survey. Stroke. 2002;33(5):1183–8.
Hankey GJ. B vitamins for stroke prevention. Stroke Vasc Neurol. 2018;3(2):51–8.
Yang Q, et al. Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation. 2006;113(10):1335–43.
Keum N, et al. Calcium intake and colorectal cancer risk: dose-response meta-analysis of prospective observational studies. Int J Cancer. 2014;135(8):1940–8.
Martineau AR, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.
Wolsk HM, et al. Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: a combined analysis of two randomized controlled trials. PLoS ONE. 2017;12(10):e0186657.
Machisio P, et al. Vitamin D supplementation reduces the risk of acute otitis media in otitis-prone children. Pediatr Infect Dis J. 2013;32(10):1055–60.
Keum N, Giovannucci E. Vitamin D supplements and cancer incidence and mortality: a meta-analysis. Br J Cancer. 2014;111(5):976–80.
Manson JE, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380(1):33–44.
Mokry LE, et al. Vitamin D and risk of multiple sclerosis: a Mendelian randomization study. PLoS Med. 2015;12(8):e1001866.
Munger KL, et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296(23):2832–8.
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Giovannucci, E. Nutritional epidemiology: forest, trees and leaves. Eur J Epidemiol 34, 319–325 (2019). https://doi.org/10.1007/s10654-019-00488-4
- Cardiovascular diseases