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Human nutrition and genetic variation Patrick J. Stover Abstract Human genetic variation is a determinant of nutrient efficacy and of tolerances and intolerances and has the potential to influence nutrient intake values (NIVs). Knowledge derived from the comprehensive identification of human genetic variation offers the potential to predict the physiological and pathological consequences of individual genetic differences and prevent and/or manage adverse outcomes through diet. Nutrients and genomes interact reciprocally; genomes confer differences in nutrient utilization, whereas nutrients effectively modify genome expression, stability, and viability. Understanding the interactions that occur among human genes, including all genetic variants thereof, and environmental exposures is enabling the development of genotype-specific nutritional regimens that prevent disease and promote wellness for individuals and populations throughout the life cycle. Genomic technologies may provide new criteria for establishing NIVs. The impact of a gene variant on NIVs will be dependent on its penetrance and prevalence within a population. Recent experiences indicate that few gene variants are anticipated to be sufficiently penetrant to affect average requirement (AR) values to a greater degree than environmental factors. If highly penetrant gene variants are identified that affect nutrient requirements, the prevalence of the variant in that country or region will determine the feasibility and necessity of deriving more than one AR or upper limit (UL) for affected genetic subgroups. Key words: Genome, nutrients, nutrition, polymorphism, requirements, variation The author is affiliated with Cornell University, Ithaca, New York, USA. Please direct queries to the author: Patrick J. Stover, Cornell University, Division of Nutritional Sciences, 315 Savage Hall, Ithaca, NY 14853, USA; e-mail: pjs13@cornell.edu. Introduction Knowledge derived from the comprehensive identification of human genetic variation offers the potential to predict, prevent, and/or manage physiological and pathological consequences of individual genetic differences. Genetic variation contributes to human disease susceptibility, optimal nutritional requirements, food tolerance, drug efficacy, inflammatory responses, longevity, and virtually every human phenotype [1–8]. Nutrients and pharmaceuticals are two exposures that are proven to be effective in modifying genome function and stability for benefit, but whose utilization and efficacy are modified by human genetic variation. Dietary guidelines, both food- and nutrient-based, are established to assist individuals and populations achieve adequate dietary patterns to maintain health. Their derivation and goals evolve continuously in response to new knowledge [9, 10]. When possible, guidelines for single nutrients and other food components are scientifically and quantitatively derived, and these numeric standards are essential to validate the efficacy of food-based guidelines [10]. Nutrient requirements vary within all human populations and can be modified by age, sex, and life stage, among other factors. Therefore, numeric standards are often derived separately for population subgroups. It is established that genetic variation can modify the efficacy, dosage, and safety of pharmaceutical agents [5] and tolerance for certain foods [11]. However, the contribution of genetics to optimal nutrient requirements within and among human populations remains to be evaluated rigorously. This report focuses on advancements in our understanding of the human genome and the emerging application of the genome sciences to identify genetic variation that affects optimal nutrient requirements and food tolerance within and among populations, understand the role of nutrients and dietary components in modifying genome function for benefit and the intake levels required to do so, understand both the benefits and the risks of population-based nutrition policies to subgroups, and develop genome-based Food and Nutrition Bulletin, vol. 28, no. 1 (supplement) © 2007, The United Nations University. S101
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Contents International harmonizatio
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Executive summary Harmonization of
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Executive summary [11]. These are l
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Executive summary and converted to
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Executive summary very rapidly and
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Executive summary References Concep
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Introduction Janet C. King and Cutb
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Introduction References 1. King JC,
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Terminology and framework for nutri
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Nutrient risk assessment: Setting u
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Setting upper levels for nutrient r
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Establishing nutrient intake values
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Dietary guidelines and nutrient int
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International Dietary Harmonization
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