Examining Special Nutritional Requirements in Disease States Proceedings of a Workshop (2018) / Chapter Skim
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5 Building the Evidence Base: Research Approaches for Nutrients in Disease States
5 Building the Evidence Base: Research Approaches for Nutrients in Disease States
Pages 77-100
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From page 77... ...
Craig Venter Institute, delivered the next presentation, which examined innovative research designs aimed at determining efficacy of interventions. Two presentations then provided case examples of the issues involved in building an evidence base for special nutrient requirements for complex diseases.
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. Adapting the Dietary Reference Intake Approach to Special Nutrient Requirements MacFarlane continued, saying that the DRI approach has some fundamental aspects that could be adapted and potentially applied to special nutrient requirements and disease states.
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Applying the Dietary Reference Intake Risk Assessment Framework to Disease States MacFarlane then turned her attention to applying this framework to nutrient requirements in specific disease states, arguing that some aspects of the DRI risk assessment approach are fundamental to establishing special nutrient requirement intake values in disease states. Establishing Causality and Selecting Health Outcomes When establishing causality, it is necessary to have a high level of confidence that an association exists between the exposure or intake of a
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From page 80... ...
Essentially, a lower level of certainty of that relationship between the exposure and the clinical outcome or chronic disease exists, and it is often necessary to rely on the use of intermediate outcomes. MacFarlane then posed the question of how these relationships change when considering nutrient requirements for specific disease states.
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FIGURE 5-3 Nutrient requirements in disease states. NOTES: The direction of the nutrient–disease relationship differs depending on which outcome is addressed by nutrient intake and whether it demonstrates an intake–response relationship.
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Approaches to setting special nutrient requirements must consider the likelihood that a paucity of evidence exists. Future committees will have to grapple with questions about the acceptability of a lower level of evidence in the causal relationship and the ability to conduct dose–response modeling.
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. In summary, MacFarlane said that aspects of the DRI risk assessment approach are applicable and adaptable to determining special nutrient requirements in disease states, but that any adaptation of the approach must be transparent.
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When classifying and evaluating human nutrient needs in disease states, it is desirable to have a good indicator or biomarker of the disease itself and its severity. In addition, it is desirable to have measures that indicate whole body nutritional status, biomarkers for normal physiological function and clinical outcomes, and predictive biomarkers in terms of future chronic disease risk that may even be independent of the current disease state.
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n org) , which seeks to examine the relationship between inflammation and biomarkers, contends that acute and chronic inflammation can modify nutrient biomarker measures and inflammation can have a direct effect on actual nutrient status.
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4 This section summarizes information presented by Nicholas Schork.
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Personal Versus Population Thresholds Schork continued with another aspect of N-of-1 trials, which illustrates personal versus population thresholds. He used the example of a clinician with cholesterol measures on 25 individuals.
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To illustrate, Schork noted that individual cancer patients' tumors exhibit perturbations and certain drugs can uniquely counteract the patho hysiology p induced by those specific tumor mutations. To identify matches between tumor perturbations that might be unique to a small set of the population and specific drugs, cancer clinicians would have to run many trials with small numbers of patients, and that would be inefficient.
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From page 89... ...
Schork concluded his presentation by noting that these issues raise the question of whether all the algorithms that are being developed by different groups should be vetted in a regulated environment. EXAMPLES OF A COMPLEX DISEASE: INFLAMMATORY BOWEL DISEASE5 In wet bench research that uses animal model systems, animals have defined environmental conditions and genetics and a monotonous diet.
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This provides an opportunity to use the best technologies in human subject research to examine how altering the environment of the gut, perhaps through dietary interventions, might be beneficial in treating IBD. The paradigm being used to support this notion, said Wu, is that diet is epidemiologically associated with IBD, gut microbiota unquestionably play a role in the pathogenesis of IBD, and diet can shape the composition of the microbiota, which leads to the production of many different types of metabolites.
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2012. Food and the gut microbiota in inflammatory bowel diseases: A critical connection.
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These results suggest that the main impact of diet on the human plasma metabolome is a direct effect on the host with a smaller contribution working through the gut microbiota. EXAMPLES OF A COMPLEX DISEASE: CANCER7 The World Cancer Research Fund and the American Institute for Cancer Research (WCRF-AICR)
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Overall, the dietary patterns recommended in the Dietary Guidelines for Americans are consistent with the WCRF-AICR recommendations. Effect of Nutrients on the Cancer Continuum Clinton then addressed how different phases of the cancer continuum have implications for nutrition and nutrient requirements.
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Achieving cures in such types of malignancy where different metastatic sites with very different mutational patterns exist in a single individual is very difficult. Special Nutrient Requirements in Cancer Clinton concluded his presentation with the following comments about DRIs and cancer: • Developing DRIs for cancer prevention using the public health approach should and will continue.
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From page 95... ...
This included the tension of the single nutrient versus the dietary pattern, the tension of genes versus the environment, the tension between understanding things at the population level versus personalized medicine, the tension of traditional RCTs versus N-of-1 study designs, and the tension between looking at final health outcomes versus intermediate biomarkers. Patient Perspectives on Developing Nutrient Recommendations To a question related to the patient perspective in establishing nutrient requirements and the feasibility of individuals changing their diet, MacFarlane responded that a regulatory body's responsibility would be to have good standards based on good evidence of what disease responds to what particular nutrient intake.
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From page 96... ...
Even though the reasons for the association may not be clear, these studies are enormously valuable because if a wet bench researcher can phenocopy the association in a culture system and/or in an animal model, it might help show more about cause-and-effect relationships that drive the biological process in human biology. What Level of Evidence Is Necessary?
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From page 97... ...
had to respond to countries who wanted to know how much folic acid should be put in the food supply. WHO used a big data approach, where they used observational data and big datasets to create a computed dose–response curve.
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Schork agreed with this point, but also commented that RCTs rarely collect enough data on any one participant to say unequivocally whether that person responded to the treatment or not. The N-of-1 study designs are intended to bring out the response phenotype in ways that are more compelling than is possible in standard RCTs.
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2017. Guiding prin ciples for developing Dietary Reference Intakes based on chronic disease.
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