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Core Concepts of Nutrition

Ian A. Macdonald and Annemie M.W.J. Schols

Key messages

• The change in body reserves or stores of a nutrient is the difference between the intake of that nutrient and the body's utilisation of that nutrient. The time-frame necessary to assess the body's balance of a particular nutrient varies from one nutrient to another.
• The concept of turnover can be applied at various levels within the body (molecular, cellular, tissue/organs, whole body).
• The flux of a nutrient through a metabolic pathway is a measure of the rate of activity of the pathway. Flux is not necessarily related to the size of the pool or pathway through which the nutrient or metabolite flows.
• Nutrients and metabolites are present in several pools in the body. The size of these metabolic pools varies substantially for different nutrients/metabolites, and a knowledge of how these pools are interconnected greatly helps us to understand nutrition and metabolism in health and disease.
• The Darwinian theory of evolution implies a capacity to adapt to adverse conditions, including adverse dietary conditions. Many such examples can be cited. Some allow for long-term adaptation and others buy time until better conditions arrive.

1.1 Introduction

Nutrition and metabolism are addressed in this textbook in an integrated fashion. Thus, rather than considering nutrients separately, this book brings together information on macronutrients, energy and substrate metabolism in relation to specific nutritional or disease states or topics (e.g. undernutrition, overnutrition, cardiovascular disease). Before considering these topics in detail, it is necessary to outline the core concepts of nutritional metabolism. The core concepts covered in this chapter are nutrient balance, turnover and flux, metabolic pools and adaptation to altered nutrient supply.

1.2 Balance

As discussed in Chapters 3 and 4, nutrient balance must be considered separately from the concepts of metabolic equilibrium or steady state. In this chapter, the concept of balance is considered in the context of the classic meaning of that term, i.e. the long-term sum of all the forces of metabolic equilibrium for a given nutrient.

The concept of nutrient balance essentially restates the law of conservation of mass in terms of nutrient exchange in the body. It has become common practice to refer to the content of the nutrient within the body as a 'store' but in many cases this is not appropriate and the term 'reserves' is better. Thus, the idea of nutrient balance is summarised by the equation:

The above equation can have three outcomes:

• Zero balance (or nutrient balance): Intake matches utilisation and reserves remain constant
• Positive balance (or positive imbalance): Intake exceeds utilisation and reserves expand
• Negative balance (or negative imbalance): Utilisation exceeds intake and reserves become depleted.

In relation to macronutrient metabolism, the concept of balance is most often applied to protein (nitrogen) and to energy. However, many research studies now subdivide energy into the three macronutrients and consider fat, carbohydrate and protein balance separately. This separation of the macronutrients is valuable in conditions of altered dietary composition (e.g. low-carbohydrate diets) where a state of energy balance might exist over a few days but be the result of negative carbohydrate balance (using the body's glycogen reserves to satisfy the brain's requirement for glucose) matched in energy terms by positive fat balance.

Balance is a function not only of nutrient intake but also of metabolic requirements and metabolically elevated requirements. Fat balance is generally driven by periods where energy intake exceeds energy expenditure (positive energy balance) and by periods when intakes are maintained below energy expenditure, such as in dieting, acute and chronic disease, hypoxia (negative energy balance). However, nutrient balance can also be driven by metabolic regulators through hormones or cytokines. For example, the dominance of growth hormone during childhood ensures positive energy and nutrient balance. In pregnancy, a wide range of hormones lead to a positive balance of all nutrients in the overall placental, fetal and maternal tissues, although this may be associated with a redistribution of some nutrient reserves from the mother to the fetus (see Chapter 6). By contrast, severe trauma or illness will dramatically induce energy and protein losses, an event due to elevated metabolic requirements unrelated to eating patterns.

Balance is not something to be thought of in the short term. Following each meal, there is either storage of absorbed nutrients (triacylglycerol [TAG] in adipose tissue or glucose in glycogen) or a cessation of nutrient losses (breakdown of stored TAG to non-esterified fatty acids or amino acid conversion to glucose via gluconeogenesis). As the period of postprandial metabolism is extended, the recently stored nutrients are drawn upon and the catabolic state commences again. This is best reflected in the high glucagon to insulin ratio in the fasted state before the meal and the opposite high insulin to glucagon ratio during the meal and immediate postprandial period. However, when balance is measured over a sufficient period, which varies from nutrient to nutrient, a stable pattern can be seen: zero, positive or negative (Figure 1.1).

Figure 1.1 Positive, zero and negative nutrient balance over time with fluctuations upwards and downwards within that time.

It is critically important with respect to both obesity and malnutrition that the concept of balance is correctly considered. While at some stage energy balance must have been positive to reach an overweight or obese stage, once attained most people sustain a stable weight over quite long periods.

In the context of the present chapter, it is worth reflecting on the reasons why the time taken to assess energy balance correctly varies for different nutrients. Because of differences in capacity and mobilisation as summarised below and explained in Chapters 4 and 12, calcium balance, for example, will require months of equilibrium while fat balance could be equilibrated in days or at most a few weeks.

• Fat and adipose tissue (Chapter 4)
  • There is a very large capacity to vary the body's pool of adipose tissue. One can double or halve the level of the fat reserves in the body.
  • The capacity to vary the level of TAG in blood en route to adipose tissue can vary.
  • Almost all of the TAG reserves in adipose tissue are exchangeable.
• Calcium and bone (Chapter 12)
  • The human being must maintain a large skeleton as the scaffold on which the musculature and organs are held.
  • There is a very strict limit to the level of calcium that can be transported in blood. Excess or insufficient plasma calcium levels influence neural function and muscle function, since calcium is a major component of muscle and nerve function.
  • Only a small fraction (the miscible pool) of bone is available for movement into plasma.

1.3 Turnover

Although the composition of the body and of the constituents of the blood may appear constant, the component parts are not static. In fact, most metabolic substrates are continually being utilised and replaced (i.e. they turn over). This process of turnover is well illustrated by considering protein metabolism in the body. Daily adult dietary protein intakes are in the region of 50-100 g and the rates of urinary excretion of nitrogen match the protein intake. However, isotopically derived rates of protein degradation indicate that approximately 350 g is broken down per day. This is matched by an equivalent amount of protein synthesis per day, with most of this synthesis representing turnover of substrate (i.e. degradation and resynthesis) rather than being derived de novo from dietary protein (see Chapter 5).

Similar metabolic turnover occurs with other nutrients; glucose is a good example, with a relatively constant blood glucose concentration arising from a match between production by the liver and utilisation by the glucose-dependent metabolic tissues (see Chapter 4).

The concept of turnover can be applied at various levels within the body (molecular, cellular, tissue/organs, whole body). Thus, within a cell, the concentration of adenosine triphosphate (ATP) remains relatively constant, with utilisation being matched by synthesis. Within most tissues and organs, there is a continuous turnover of cells, with degradation and death of some cells matched by the production of new ones. Some cells, such as red blood cells, have a long lifespan (c. 120 days) while others, such as platelets, turn over in a matter of 1-2 days. In the case of proteins, those with very short half-lives have amino acid sequences that favour rapid proteolysis by the range of enzymes designed to hydrolyse proteins. Equally, those with longer half-lives have a more proteolytic-resistant structure.

A major advantage of this process of turnover is that the body is able to respond rapidly to a change in metabolic state by altering both synthesis and degradation to achieve the necessary response. One consequence of this turnover is the high energy cost of continuing synthesis. There is also the potential for nutrient imbalance and metabolic...