Nutrigenomics and the Future of Nutrition Proceedings of a Workshop (2018) / Chapter Skim
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4 Nutrigenomics Applications: Dietary Guidance and Food Product Development
4 Nutrigenomics Applications: Dietary Guidance and Food Product Development
Pages 61-84
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From page 61... ...
Now in session 2, Johnson continued, the focus would be shifting to "how we really take that information and move it forward in a way that makes a difference in people's lives." This chapter summarizes the session 2 presentations and discussion, with highlights provided in Box 4-1. NUTRIENT REQUIREMENTS AS COMPLEX TRAITS: WHAT CONSUMERS NEED TO KNOW Patrick Stover, Cornell University, began his presentation by describing an incident that had recently taken place when he missed a flight and was sent an Uber driver to accommodate his changed travel plans.
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From page 62... ...
Given this knowledge, one could develop nutritional solutions, or medical foods, to bypass roadblocks known to be asso ciated with particular nutrition-related health outcomes. (Zeisel)
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From page 63... ...
, it means considering DRIs as ranges, not point estimates. He noted further that, beyond considering integrative biomarkers, thinking about chronic disease endpoints requires considering biomarkers of aging and how they interact with biomarkers of nutrition.
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From page 64... ...
instead of DRIs. He noted that these requirements would include medical foods, which provide nutrients that may not be accessible from the food supply in the quantity or quality one needs.
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From page 65... ...
federal government released the National Nutrition Research Roadmap, 2016–2021, which also focuses not just on the connection between nutrition and disease prevention, but on the importance of understanding individual differences in nutritional status as well (Interagency Committee on Human Nutrition Research, 2016)
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From page 66... ...
He cited as an example 23andMe, which offers a genetic test whereby consumers can learn not just about their ancestry but also what percentage of their genome is N eanderthal or Denisovan. Stover identified as a second major source of human genetic variation mutation events that subsequently extended though a population via either selection or drift.
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From page 67... ...
The T allele protein is less stable and less active, and individuals carrying that variant have a lower folate status and, all other things being equal, a higher folate requirement and greater risk for birth defects and miscarriage. However, Stover observed, if individuals with the T allele survive to adulthood, their risk of colon cancer is reduced by 70 to 80 percent if they maintain adequate folate status (Ma et al., 1999)
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From page 68... ...
Regarding the latter point, he explained that there was a paucity of data linking folic acid intake to risk of neural tube defects and that what data did exist were of low quality. However, there were data linking folic acid intake to folate concentration in red blood cells.
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From page 69... ...
= cholesterol; FVB = FVB/NJ strain mice; GTT = glucose tolerance test; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NOD = NOD/ ShiLtJ strain mice; TG = triglyceride. SOURCES: Presented by Patrick Stover on December 5, 2017, from Barrington et al., 2018.
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From page 70... ...
He then cited one example of point-of-care measurement of nutrition-related bio arkers, ex m plaining that his colleagues at Cornell University have developed what they call the Nutriphone, a smartphone-based microfluidic device. He described this device as much like a pregnancy test, except that it provides a real-time readout of 8–10 nutrient status markers, functional biomarkers, chronic disease markers, and infectious disease markers (Lee et al., 2016)
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From page 71... ...
Additionally, he himself was involved in the early startup phase of Zthera, a gene-guided medical foods company. "We've heard over and over again how metabolically different we are," Zeisel said, noting that each individual has about 50,000 common, inherited single nucleotide polymorphisms (SNPs)
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From page 72... ...
Metabolism Metabolite Nutrient No SNP Metabolite Nutrient metabolite Metabolite SNP DIET DELIVERS METABOLITE FIGURE 4-3 By delivering large amounts of a metabolite, diet can bypass, and "hide," a metabolic roadblock caused by a single nucleotide polymorphism (SNP)
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From page 73... ...
To explore this question, they removed the nutrient from their study participants' diets to see if they would develop fatty liver or liver or muscle damage caused by apoptosis. In the process, they noticed that young women needed less choline relative to both men and postmenopausal women (Fischer et al., 2007)
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From page 74... ...
. Recognizing the Involvement of Multiple SNPs While single SNP analysis is useful, Zeisel continued, as the field of nutri enomics evolves, companies will need to start recognizing the com g plexity of metabolic pathways and the involvement of both multiple pathways and multiple "hits" within pathways.
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From page 75... ...
for whom export of fat from the liver is important because their liver produces much more fat from the excess calories they consume, and for whom these polymorphisms predict the development of fatty liver. As a result of this research, Zeisel's team now has a gene test for 19 SNPs in women and 21 in men that predict susceptibility to developing fatty liver with 90 percent accuracy among people gaining weight.
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From page 76... ...
So again, he predicted the opportunity for another medical food as a solution to a blocked metabolic pathway, or pathways -- in this case the SNPs responsible for muscle breakdown during exercise. SNPs and Sperm Dysfunction: Another Example of Gene-Guided Intervention Zeisel went on to explain that when a study is conducted in humans and polymorphisms are identified that appear to be important, as was the case with choline deficiency, those polymorphisms can be knocked out in mice and other effects examined.
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From page 77... ...
If people with a polymorphism are not being challenged, he added, they will look the same as people without the polymorphism. Finally, Zeisel encouraged the workshop participants to think about medical foods, as defined by FDA, as a potentially good starting point for developing nutrigenomic products.
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From page 78... ...
"We're going to have a lot of snake oil," he ac knowledged, "but we have a lot of snake oil diets with regular foods." He emphasized that he liked the idea of medical foods as a starting point because FDA has already set some ground rules in this area. The agency has not fully defined the problem, he remarked, but with what it has defined, there is at least some oversight.
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From page 79... ...
Keeping this in mind, he said, medical foods are the only categorization that would allow for a nutritional treatment for patients with disease, as dietary supplements can only help support normal function. Zeisel clarified that he was not suggesting a medical food is the only way to start implementing nutrigenomics; rather, he was suggesting that it might be the best way to get the field started.
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From page 80... ...
He described precision medicine as a powerful movement at present, with the support of both federal researchers and many large medical schools, and as a subject being taught to every medical student today. "I think everybody will be practicing that way," he said, so "this will just look the same to them." Stover suggested that the formulated medical foods being used to treat loss of function in individuals with inborn errors of metabolism also serve as a model.
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From page 81... ...
Stover responded that insurance coverage is one of the greatest challenges with medical foods -- for example, for children with inflammatory bowel disease who are dependent on a liquid diet for their survival. It is very difficult, he observed, for those families to get insurance to pay for these products.
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From page 82... ...
If a test shows that someone has a specific metabolic effect, for example, and there is a medical food designed to treat that effect, Zeisel would argue that prescribing that medical food as an intervention poses no greater risk than would be the case if there were no such option. Zeisel suggested that eventually, babies will be genotyped at birth.
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From page 83... ...
Then the question becomes, he suggested, how many subgroups there can be. "But there is no way I think we are going to be able to walk away from having population-based nutritional requirements," he asserted, "because that's the basis of the food supply.
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From page 84... ...
Stover replied that many databases are available to aid in developing the architecture of a metabolic network, such as those for gene expression, SNPs, the proteome, and the transcriptome, any of which can be used to set a range for or circumscribe the magnitude of an effect at any one node. Yet, he added, although the information is available, one must have some familiarity with the field to understand it.
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