Food Structure for Nutrition

Danielle G. Lemay, Cora J. Dillard and J. Bruce German

1.1 Introduction

The great tradition of nutrition research has seen the creation of an unprecedented knowledge base of the essential nutrients, together with their absolute quantitative requirements at different life stages, and the pathological phenotypes experienced by populations who fail to consume sufficient quantities of them. The research that was necessary to assemble this knowledge base of essential molecules is one of the life science's great achievements. In retrospect, the achievement was made possible by some key strategic decisions by nutrition scientists. First, there was the critical decision for nutrition to become a molecular science. The object of the study of nutrition, namely food, was physically and conceptually disassembled into individual molecules. By eliminating food structure from nutrition research, it became possible to feed animals with purified diets in which specific suspected nutrients were explicitly included or assiduously removed. If the molecule was an essential nutrient, its elimination from a diet fed to a growing, reproducing animal model would produce overt deficiency symptoms. This so-called 'fault model' of nutrient discovery was critical to scientific studies designed to identify the essential nutrients. As a result of this very successful research strategy, all of the vitamins, minerals, amino acids, and fatty acids that are essential to the growth and reproduction of animals and humans are now known.

The knowledge of the nutrients that are necessary for humans shifted the public health emphasis to strategies designed to ensure that populations consume diets that achieve adequacy of all of the essential nutrients, and are thus sufficient to prevent deficiency diseases. An underlying assumption in this public health emphasis and focus on essential nutrients was that diets containing all of the essential nutrients in adequate amounts would largely eliminate diet-related diseases. But it has become disturbingly clear that it is possible to obtain all of the essential nutrients and still consume diets that are sub-optimal for overall health. In fact, poorly balanced diets are now recognized to be one of the leading causes of metabolic diseases around the world. Understanding how diet can produce such diseases is leading to a much more comprehensive understanding of the interactions between food components and health.

To understand food's broader role in nutrition, it will be necessary not only to go beyond essential nutrients, and to redesign nutritional models and experiments, but also to reconsider the meaning of 'health' itself. Health must be understood in terms of the wide diversity of normal metabolic states of humans. The recent epidemics in heart disease, obesity, diabetes, hypertension, and osteoporosis indicate that health can deteriorate in response to imbalanced diets almost as quickly as it can deteriorate in the absence of essential nutrients. In particular, there is an immediate need to understand the role of diet and foods in managing food intake and in regulating whole body energy status. Most nutritional measures of essential nutrients and their status have been taken in the fasted condition to avoid confounding chronic status with acute food intake. It is now becoming apparent that variations in the dynamic or temporal responses to food components are also important to overall health. Nutrition research must, therefore, embrace the entire continuum of the fed state, leading to an understanding of how rapidly foods are digested, absorbed, and metabolized, and how these temporal and special events relate to overall health. With this perspective in mind, the influence of food structure on the dynamics of varying post-prandial metabolic states should be studied in mechanistic detail.

Food itself must also be understood comprehensively as multi-component, multi-phasic ensembles of biomaterials. Clearly, optimal diets are more than just the essential nutrients. Notably, several aspects of foods have emerged that were virtually ignored by nutritional research in the scientific pursuit of essential nutrients. Perhaps the most important omission was food structure itself. The science of food biomaterials must now deliver food structure as a fully controllable variable set to nutrition research. For nutrition researchers to understand the role of physical, colloidal, and macromolecular structure, these must be studied as independent variables in nutrition studies. Knowledge of food structure must, therefore, become highly predictive – not just descriptive.

1.2 Food Structure and Nutrition – Then and Now

1.2.1 The Past

The science of nutrition is the knowledge repository for the understanding of essential nutrients, their quantitative requirements, and the mechanisms behind their essentiality. Few achievements in science have been as complete, or as rapidly brought to public health practice, as the identification of nutrients essential for humans. The decision taken early in the 20th century to disassemble food commodities into molecules and study essentiality as a molecular phenomenon was the defining event in molecular nutrition, and few decisions in the history of science have been so successful. The concept of specific molecules as essential amines was initiated by Casimir Funk, who effectively spawned molecular nutrition with the isolation of vitamin Bl (thiamin) in 1912, as reviewed by Jukes; and within 40 years the concept of essential nutrients was ostensibly complete.

This great legacy of discovery paved the way for the eradication of diseases caused by nutrient deficiencies. However, some of the important strategies of nutrient discovery are proving to be debilitating to the future growth of nutrition as a field. This is particularly true as nutrition emerges with the goal of guiding diets to improve overall health. For example, while disassembling foods into molecules enabled the differentiation of essential from nonessential nutrients, it left a prevailing assumption that food per se is immaterial to the provision of essentiality, and to health in general. Similarly, by establishing essential nutrients, the underlying assumption was that they were essential for all humans; thus, varying nutritional requirements within individuals among the population remained largely ignored. By defining bioavailability as the integration of the pharmacokinetic curve of an ingested nutrient in blood relative to the same nutrient when injected, the goal became a bioavailability of unity; hence, the foods themselves – in particular those with a degree of complexity of food matrices that may reduce bioavailability – were by definition deleterious. By defining an adequate diet as that producing adequate tissue levels of nutrients in the fasted condition, the relationship of the structure of foods and diet to the dynamics of the fed state has remained largely unstudied. Needless to say, if the dynamics of food and nutrient delivery remain unknown, they will continue to be unappreciated in terms of the value of food structure to its nutritive value.

1.2.2 The Present

The emergence of diseases of metabolic dysregulation associated with variations in diet is forcing scientists to refine the traditional views of nutrition. Diet affects health in more ways than simply through providing essential nutrients: it includes various aspects of chronic metabolic regulation. The science of nutrition has not yet built an understanding of this complexity. Furthermore, whereas recommendations for essential nutrients can be quite broad for the entire population, humans vary in their responses to diets as they affect metabolism, and the same diets fed to different individuals may develop quite distinctly different health consequences. Therefore, as the field of nutrition faces this new challenge of (re-)discovering the importance of food, nutrition scientists will also need to change their perspectives of health.

While food structure and nutrition have not been well studied, there are clear indications of the importance of the dynamics of food digestion to health from many aspects of ongoing scientific research. The most vivid is the variation in rate of absorption of the simple nutrient glucose. Although food structure has not been explicitly specified as an independent variable, for many years the rate of glucose delivery to blood has been included as an indicator of food as the glycemic index. Numerous studies have documented the effect of glycemic index in accounting for variations in metabolic response to particular diets. Even more impressively, as glycemic index has been included as an independent variable in larger health issues, this simple surrogate reflection of food structure is being recognized as important to many end points that are not typically thought of as being related to food structure. For example, Taylor and co-workers have shown that glycemic index as a dietary variable was associated with an almost threefold increase in risk of macular degeneration in the Nurses' Health Study population (Figure 1). Though many more studies have documented the effects on health of the rate of absorption of glucose as glycemic index, as reviewed by Dickinson and Brand-Miller, little research has been pursued to extend these observations into a more precise understanding of the role of food structure in the dynamics of glucose delivery.

1.3 Food Structure and Bioavailability

Bioavailability is defined as the difference in delivery to blood between an oral dose and an injected dose. It is determined experimentally by measuring the dose-corrected area under curve (AUC) of a substance administered orally (po) divided by the AUC intravenous (IV):

[FORMULA NOT REPRODUCIBLE IN ASCII] (1)

If 100% of an ingested dose of a nutrient or a compound reaches the blood, the bioavailability (F) is considered to be 1. From the perspective of essential nutrients – especially when considering the risk of deficiency – the greater the bioavailability, the better the nutrient. Hence, food matrices promoting rapid and complete absorption were judged to be superior in their ability to deliver essential nutrients. Food matrices that compromised rapid absorption, as a result of their structural complexity, were considered deleterious to bioavailability and hence to nutritional value. With these rather narrow but, in context, reasonable assumptions about food structure and nutrition, food processing steps that destroyed structure were advantageous and those that created structure were considered deleterious. Now that scientific considerations have begun to broaden beyond essential nutrients to nonessential food components and the food structure itself, the absolute dynamics of the delivery of food and food components is being studied. The key question then becomes: "what is the optimal situation – is it rapid complete absorption, or slow, perhaps even incomplete, absorption?" When such a question is asked, it becomes clear that there are no biological models of optimal food structure. This being the case, it is reasonable to ponder what is the preferable biological model one would wish to interrogate to answer questions about rate and extent of absorption of nonessential food components.

1.4 Models of Food Components, Food Structure, and Health

Nutrition has begun to address the scientific questions associated with nonessential food components in the diet. To date, most of these components have been derived from plants. The vast majority of small biological molecules as candidate bioactive food components are indeed derived from secondary metabolism in plants. The total number of secondary plant metabolites is estimated to exceed 2 x 105. Nonetheless, in attempting to establish appropriate food components for nourishment beyond the essential nutrients, it is reasonable to ask what was the driving force for the emergence of these secondary metabolites within plants during evolution? For many of these compounds and their respective pathways, the divergence of secondary metabolism was driven by the competitive advantage for those plants to avoid predation. Because animals were a conspicuous source of predation of plants, much of the secondary metabolism of plants evolved explicitly by Darwinian selective pressure to avoid being eaten by animals. Thus, quite the opposite of providing compounds to improve animal health, plant secondary metabolism evolved to produce compounds that were explicitly toxic to animals. Examples of the success of this evolutionary pressure abound, from soybean trypsin inhibitors to alkaloids.' Thus, although the plant kingdom and the rapidly arriving plant genomes are interesting targets for the development of knowledge of toxicity and anti-nutritive components, it is difficult to defend plants and plant metabolites per se as targets for healthful food structures.