Variation in how individuals metabolize nutrients (i.e., metabolic heterogeneity) influences our nutritional requirements, so the ideal diet for one person may be different from the ideal diet for some one else. The scientific area of study that encompasses metabolic heterogeneity is known as precision nutrition. In a recent article, “Precision (Personalized) Nutrition: Understanding Metabolic Heterogeneity,” founding director of the NRI Steven Zeisel, MD, PhD, describes some of the causes of metabolic heterogeneity and provides his assessment of how precision nutrition can be practically implemented at a large scale and some of the challenges such implementation faces.

Causes of metabolic heterogeneity:  Differences in individuals’ requirements for nutrients can arise through differences in nutrient absorption, processing, or elimination. There are numerous contributors to metabolic heterogeneity, and one may act independently or synergistically with another. Thus, the overall landscape defining metabolic heterogeneity is highly complex, spanning genetic, epigenetic, microbiome, and other contributions.

Genetic differences:  Comparatively speaking, techniques for mapping the human genome and identifying specific differences (single nucleotide polymorphisms or SNPs) are straightforward and well established. Consequently, our understanding of genetic contributions to nutrition and metabolic heterogeneity are most advanced. Specific examples include SNPs in genes regulating metabolism of caffeine, choline, vitamin D, and lipids. Other examples include SNPs that modify satiety and physiological responses to diet interventions. Zeisel also notes that combinations of specific SNPs may be synergistic with respect to susceptibility to diet-induced diseases such as fatty liver. To date there are hundreds of known SNPs that contribute to metabolic heterogeneity across the human population, and it is likely that eventually we will identify thousands of such SNPs.

Epigenetic differences:  Cells in different tissues have highly diverse functions despite sharing a common genetic code. Here, gene expression is regulated by what are known as epigenetic mechanisms. A common mechanism of epigenetic gene regulation is DNA methylation. This methylation, in turn, can be influenced by availability, typically from diet, of nutrients such as choline, vitamin B12, and vitamin B6. Hence, different diets can result in different patterns of gene expression, particularly at early stages of growth and development. Notably, some of these differences can persist even if diets are equalized later in life.

Microbiome differences:  Humans live in a mutually beneficial relationship with numerous colonies of microbes collectively known as the microbiome (a recent estimate suggests that a person has more microbe cells than human cells). Microbiomes differ from person to person and are influenced by multiple environmental and genetic factors. These microbiomes derive their nutrients from the host (i.e., us), and differences in what microbiota consume and produce thus influence, to some degree, what is available to human cells, further contributing to our metabolic heterogeneity.

Implementation of precision nutrition:  The use of the modifier “precision” rather than “personalized” is intentional and based on the recognition that because of the many facets that influence nutritional needs, it is impractical to accurately analyze every individual. Rather, precision nutrition seeks to identify various subgroups with distinct nutritional needs and to continually refine the subgroups as more research and information becomes available. This also highlights some of the challenges that lie ahead for broad implementation of precision nutrition-informed policy: 1) While collecting genetic and microbiome data from populations is within current technologies, collecting nutritionally relevant epigenetic data is not. 2) There are few studies that have collected sufficiently broad types of data (e.g., genetic, epigenetic, microbiome, diet, environmental exposure) from the same group of people. 3) Data collection aside, understanding the functional implications of genetic/epigenetic/microbiome differences still requires substantial research. 4) This ambiguity presents ethical, legal, and practical challenges to the design and management of clinical research.

In this regard a new study is noteworthy: The Nutrition for Precision Health Study is a component of the National Institutes of Health’s All of Us Research Program and is specifically designed to record genetic, microbiome, diet, and environmental exposure data from nearly 10,000 participants across the U.S. with the intention of developing computational algorithms to define nutritional subpopulations and assist with the implementation of precision nutrition.

Zeisel, SH (2020). Precision (Personalized) Nutrition: Understanding Metabolic Heterogeneity. Annu Rev Food Sci Technol. 11:71-92.