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.
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