It is important to note that the assumptions discussed in the last article are not arbitrary to the biomedical model, but legitimized through common sense in the context of a given research topic (32). A common-sense approach to nutrition, therefore, is one which can legitimize a modified approach to scientific inquiry into diet-disease relationships. Although not exhaustive, a number of potential features and alternatives could modify the approach.
The first is to move away from the narrow focus on isolated nutrients/compounds, to emphasizing food as the exposure of interest and design “whole-diet” interventions which reflect that the fundamental unit in nutrition is food (11,37). The emerging evidence for food-based interventions is encouraging, with the PREDIMED intervention to consume 4-tablespoons extra-virgin olive oil per day, or consumption of 30g nuts per day, leading to a 30% reduction in cardiovascular disease risk over 4.5-years (40). Similarly, the Dietary Approaches to Stop Hypertension [DASH] diet, which emphasized specified servings of vegetables, fruit, low-fat dairy, poultry and fish, now has a well-established evidence base for reductions in cardiovascular risk as well (41,42).
The first is to move away from the narrow focus on isolated nutrients/compounds, to emphasising food as the exposure of interest and design “whole-diet” interventions which reflect that the fundamental unit in nutrition is food.
A second important modification of trial design for nutrition is moving from purely explanatory RCTs (which attempt to guarantee internal validity based on presuppositions) to more pragmatic trials (8,32). Nutrition interventions are behavioral interventions that often have high drop-out rates, compliance issues, and a disproportionate level of support in the intervention arm generating claims of ‘bias’ (6,8). Pragmatic trials have greater external validity, and this generalizability will be more applicable if the subjects are assigned to consume particular foods or diet patterns (8). Trials assessing participant adherence to a diet pattern or to behavioral strategies would also have more real-world applicability.
With regard to the issue of a lack of placebo control, the use of crossover designs could be increased, providing a more valid comparison of the effects of different degrees of exposure within individuals. This could also uncover the potential reasons for individual differences in response (if any), which could then better inform future study designs. Of course, the potential limitation of crossover designs is residual effects of the first intervention, but no one design is perfect, and in nutrition we always take each design for what it offers, and look at the total body of research when attempting to draw conclusions.
A Nutrition-Specific Evidence Framework
Waiting for nutrition recommendations to be grounded in RCTs would paralyse the scientific process, and the rigid application of the biomedical model and explanatory RCT emphasis has led to a restrained assessment of nutrition (8,12). Nutrition science can overcome these limitations to grow a more informative and actionable evidence-base by shifting the paradigm away from an emphasis on nutrients and mechanisms of action, to overall dietary patterns and foods as the relevant exposures (11,36,39).
An approach that prioritizes diet patterns and foods as the departure point may be considered research “from the top down” (36). Focusing on diet patterns accounts for the polyvalent nature of foods and food synergy. An incomplete mechanistic understanding therefore becomes a secondary consideration to the overall health effects of the composite of foods in a diet pattern (11,12,24,39). Because there is no singular effect of a nutrient in any “absolute” sense, the health effects of nutrient substitution in diets can be captured in the study of diet patterns (11,12).
Nutrition science can overcome these limitations to grow a more informative and actionable evidence-base by shifting the paradigm away from an emphasis on nutrients and mechanisms of action, to overall dietary patterns and foods as the relevant exposure.
Furthermore, a key benefit of emphasizing research on dietary patterns is the ability to translate findings into policy well before underlying mechanisms are fully understood (12). This “top-down” research approach facilitates more pragmatic, food-based RCTs to confirm epidemiologic observations of diet patterns. It takes into consideration the biological relevance of how a nutrient is consumed in an overall diet pattern, with particular focus on the whole food as the exposure.
Finally, it overcomes the limitation of ‘methodolatry’, the veneration of the RCT as the only valid means of investigation (44). Holding nutrition to an emphasis on biomedical-style RCT’s will not only delay the scientific process, but discounting nutritional epidemiology may mean these suggested large, simple RCT’s spend many years and resources answering the wrong questions (6,9).
The salient fact is that RCT’s are not an absolute necessity to formulate pragmatic conclusions about diet and health and inform public policy (6,7,8). The future of nutrition science is to continue to improve methodology for well-designed prospective cohort studies, while conducting pragmatic intervention studies, collectively supported by ongoing animal model research and human mechanistic studies (6,7,8).
Because we inevitably have gaps in the literature in nutrition, the application of a medical standard precautionary principle means that many simple, low-cost, no-risk, and potentially beneficial food-based interventions are confined to academic journals. To overcome this, a nutrition-specific framework for assessing evidence is required: such a common-sense framework for considering how we use the evidence base that is available has been advanced (45), and provides it is an eminently pragmatic framework for how to assess the evidence for nutrition:
5 questions to assess nutrition evidence:
- Are there plausible mechanisms through which the nutrient, food or diet might help?
- Is there some evidence from clinical trials in favor of the nutrient, food or diet?
- Is there evidence of marginal or excessive intakes at the population level?
- Is the food, nutrient, or diet broadly consistent with “healthy eating” messages?
- Are there populations who consume this nutrient, food or diet at this level, without obvious harmful effects? (45)
Questions 1 and 2 are relevant to the consideration of drugs in the biomedical model, however, questions 3-5 are only relevant to nutrition. Foods have a multiplicity of constituents which contribute to improve health or to increase disease risk, and while they can be analyzed, their metabolism is often more complicated and often incompletely understood. Determining precise, specific metabolic pathways, actions, and effects is often more difficult than with medicines.
This framework provides a means to assess evidence for nutrition in the context of an overall diet pattern and how a nutrient is consumed, with particular focus on the whole food as the relevant exposure. Within this framework, consideration should be given not only to the p-value statistical significance, but also to the biological relevance of the outcome. Such a framework is complementary to “top-down” diet pattern research, as it provides a means to assess the evidence for the effect of a given food. With the limitations of the reductionist biomedical model for the study of nutrition, a combination of a top-down emphasis in research and more pragmatic use of the available evidence-base may result in more directive, accessible, and translation food guidelines for public health.
- Heaney R. Nutrients, Endpoints, and the Problem of Proof. The Journal of Nutrition. 2008;138(9):1591-1595.
- Vandenbroucke J. Adolphe Vorderman’s 1897 study on beriberi: an example of scrupulous efforts to avoid bias. Journal of the Royal Society of Medicine. 2013;106(3):108-111.
- Mozaffarian D. Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity. Circulation. 2016;133(2):187-225.
- Messina M, Lampe J, Birt D, Appel L, Pivonka E, Berry B et al. Reductionism and the Narrowing Nutrition Perspective. Journal of the American Dietetic Association. 2001;101(12):1416-1419.
- Trepanowski J, Ionnidis J. Perspective: Limiting Dependence on Nonrandomized Studies and Improving Randomized Trials in Human Nutrition Research: Why and How. Advances in Nutrition. 2018;Jul 1;9(4):367-377.
- Satija A, Stampfer M, Rimm E, Willett W, Hu F. Perspective: Are Large, Simple Trials the Solution for Nutrition Research?. Advances in Nutrition. 2018;9(4):378-387.
- Satija A, Yu E, Willett W, Hu F. Understanding Nutritional Epidemiology and Its Role in Policy. Advances in Nutrition. 2015;6(1):5-18.
- Hébert J, Frongillo E, Adams S, Turner-McGrievy G, Hurley T, Miller D et al. Perspective: Randomized Controlled Trials Are Not a Panacea for Diet-Related Research. Advances in Nutrition. 2016;7(3):423-432.
- Maki K, Slavin J, Rains T, Kris-Etherton P. Limitations of Observational Evidence: Implications for Evidence-Based Dietary Recommendations. Advances in Nutrition. 2014;5(1):7-15.
- Willett W. Nutritional epidemiology. New York [etc.]: Oxford University Press; 2013.
- Jacobs D, Steffen L. Nutrients, foods, and dietary patterns as exposures in research: a framework for food synergy. The American Journal of Clinical Nutrition. 2003;78(3):508S-513S.
- Tapsell L, Neale E, Satija A, Hu F. Foods, Nutrients, and Dietary Patterns: Interconnections and Implications for Dietary Guidelines. Advances in Nutrition. 2016;7(3):445-454.
- JAIN M, HOWE G, HARRISON L, MILLER A. A Study of Repeatability of Dietary Data Over A Seven-Year Period. American Journal of Epidemiology. 1989;129(2):422-429.
- Post G, Vente W, Kemper H, Twisk J. Longitudinal trends in and tracking of energy and nutrient intake over 20 years in a Dutch cohort of men and women between 13 and 33 years of age: The Amsterdam growth and health longitudinal study. British Journal of Nutrition. 2001;85(03):375.
- Mikkilä V, Räsänen L, Raitakari O, Marniemi J, Pietinen P, Rönnemaa T et al. Major dietary patterns and cardiovascular risk factors from childhood to adulthood. The Cardiovascular Risk in Young Finns Study. British Journal of Nutrition. 2007;98(01):218.
- Joshipura K, Ascherio A, Manson J, Stampfer M, Rimm E, Rimm E et al. Fruit and Vegetable Intake in Relation to Risk of Ischemic Stroke. JAMA. 1999;282(13):1233.
- Hooper L, Martin N, Abdelhamid A, Davey Smith G. Reduction in saturated fat intake for cardiovascular disease. Cochrane Database of Systematic Reviews. 2015;.
- Mozaffarian D, Micha R, Wallace S. Effects on Coronary Heart Disease of Increasing Polyunsaturated Fat in Place of Saturated Fat: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS Medicine. 2010;7(3):e1000252.
- Dehghan M, Mente A, Zhang X, Swaminathan S, Li W. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study. Lancet. 2017;390:2050–62.
- Wallström P, Sonestedt E, Hlebowicz J, Ericson U, Drake I, Persson M et al. Dietary Fiber and Saturated Fat Intake Associations with Cardiovascular Disease Differ by Sex in the Malmö Diet and Cancer Cohort: A Prospective Study. PLoS ONE. 2012;7(2):e31637.
- Li Y, Hruby A, Bernstein A, Ley S, Wang D, Chiuve S et al. Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease. Journal of the American College of Cardiology. 2015;66(14):1538-1548.
- Barnard N, Willett W, Ding E. The Misuse of Meta-analysis in Nutrition Research. JAMA. 2017;318(15):1435.
- Hernan M, Robbins J. Estimating causal effects from epidemiological data. Journal of Epidemiology & Community Health. 2006;60(7):578-586.
- Hill A. The environment and disease: association or causation?. Journal of the Royal Society of Medicine. 1965;58(5):295-300.
- Aune D, Keum N, Giovannucci E, Fadnes L, Boffetta P, Greenwood 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;:i2716.
- Malik V, Hu F. Sweeteners and Risk of Obesity and Type 2 Diabetes: The Role of Sugar-Sweetened Beverages. Current Diabetes Reports. 2012;12(2):195-203.
- Mozaffarian D, Aro A, Willett W. Health effects of trans-fatty acids: experimental and observational evidence. European Journal of Clinical Nutrition. 2009;63(S2):S5-S21.
- Mozaffarian D, Clarke R. Quantitative effects on cardiovascular risk factors and coronary heart disease risk of replacing partially hydrogenated vegetable oils with other fats and oils. European Journal of Clinical Nutrition. 2009;63(S2):S22-S33.
- World Health Organisation. Diet, Nutrition and the Prevention of Chronic Diseases. Geneva: Joint WHO/FAO Expert Consultation; 2003.
- Blumberg J, Heaney R, Huncharek M, Scholl T, Stampfer M, Vieth R et al. Evidence-based criteria in the nutritional context. Nutrition Reviews. 2010;68(8):478-484.
- Morris M, Tangey C. A Potential Design Flaw of Randomized Trials of Vitamin Supplements. JAMA. 2011;305(13):1348.
- Zeilstra D, Younes J, Brummer R, Kleerebezem M. Perspective: Fundamental Limitations of the Randomized Controlled Trial Method in Nutritional Research: The Example of Probiotics. Advances in Nutrition. 2018;9(5):561-571.
- Engel G. The need for a new medical model: a challenge for biomedicine. Science. 1977;196(4286):129-136.
- Steinhubl S. Why Have Antioxidants Failed in Clinical Trials?. The American Journal of Cardiology. 2008;101(10):S14-S19.
- Eberhardt M, Lee C, Liu R. Antioxidant activity of fresh apples. Nature. 2000;405(6789):903-904.
- Jacobs D, Gross M, Tapsell L. Food synergy: an operational concept for understanding nutrition. The American Journal of Clinical Nutrition. 2009;89(5):1543S-1548S.
- Cespedes E, Hu F. Dietary patterns: from nutritional epidemiologic analysis to national guidelines. The American Journal of Clinical Nutrition. 2015;101(5):899-900.
- Feldman D, Pike J, Bouillon R. Vitamin D. 2nd ed. San Diego: Academic Press; 2005.
- Dawson-Hughes B, Harris S. Calcium intake influences the association of protein intake with rates of bone loss in elderly men and women. The American Journal of Clinical Nutrition. 2002;75(4):773-779.
- Estruch R, Ros E, Salas-Salvadó J, Covas M. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. New England Journal of Medicine. 2018;379(14):1387-1389.
- Vogt T. Dietary approaches to stop hypertension (DASH): Results and implications. American Journal of Hypertension. 1998;11(4):237A.
- Obarzanek E. The dash (dietary approaches to stop hypertension) diet lowers blood lipids. American Journal of Hypertension. 2000;13(6):S98.
- Jacobs D, Tapsell L. Food, Not Nutrients, Is the Fundamental Unit in Nutrition. Nutrition Reviews. 2008;65(10):439-450.
- Gorski D. “Methodolatry”: My new favorite term for one of the shortcomings of evidence-based medicine [Internet]. Science-Based Medicine. 2018 [cited 30 November 2018]. Available from: https://sciencebasedmedicine.org/methodolatry_my_new_favorite_term/
- Rex D. An Evidence-based, “Common Sense” Approach to the Evaluation of Dietary Interventions in ASD and ADHD. Food and Behaviour Research. 2010;.
About the authors:
Alan Flanagan is a lawyer and nutritionist based in Dublin, Ireland. In addition to his legal practice, Alan has a Masters in Nutritional Medicine at the University of Surrey and is pursuing his PhD. Alan founded Align Health as an online coaching practice, and as a medium to communicate evidence-based nutrition and health science to a lay audience. From working professionals to professional athletes, Alan provides science-based solutions and protocols to guide motivated individuals to their goals.Austin Baraki is a physician, strength coach, and competitive powerlifter based in Texas. His best lifts include a 615lb squat, 420lb bench press, and 675lb deadlift. In addition to being both incredibly strong and intelligent, he also has an affinity for cats. Seriously. He loves cats.