Diet and nutrition

Food guides

Many countries have developed their own dietary guides. These are often pictorial representations of nutrition recommendations and are usually regularly revised and updated. The food guides are a simple way of summarising the recommended balance of foods in the diet and provide a consistent message regarding dietary advice for the public. Examples can be found on the websites of the various national institutions for nutrition policy.

Food labelling

In most developed countries, there is public awareness of the healthy eating messages: the connections between diet, health and disease. However, to act on this knowledge, the general population needs nutritional information on specific foods, particularly on processed foods. Therefore, food labelling, quantifying the main nutrients, is important. In the United Kingdom (UK) ( Fig. 16.2 ) , such labelling is compulsory if a nutritional advantage is claimed for the product.

In recent years, manufacturers have started to include more nutritional labels with their products. In the European Union (EU), all food labelling is controlled principally by the Food Labelling Regulation 1996. All packaged food must have a label that states:

• The name of the food

• A list of ingredients in descending order of content, i.e. the first item listed is the largest ingredient

• Storage conditions and durability (best before or use-by date)

• The name and address of the manufacturer, packer or seller established within the EU.

Legislation was updated in the European parliament in 2011, aiming to promote healthier food choices to EU citizens, including such stipulations as:

• The actual food label must be visible, clear (a minimum print size) and accurate

• That energy, fat, saturated fat and carbohydrates with specific reference to salt and sugar content per 100 mL or per 100 g should be displayed. The recommended daily amount (RDA) should also be displayed

• Substances known as allergens should be displayed on the food label.

Nutrition claims (e.g. the food is a source of a particular nutrient), health claims (e.g. the food is in some way beneficial to health), and other claims for particular uses, may be made in relation to certain products.

Food labels are compulsory when nutritional advantages are claimed. Information contained on the labels should include:

• Nutrients – energy (kJ/kcal per kg), protein, fat and carbohydrates are expressed per 100 mL/100 g or per serving.

• More detailed information regarding carbohydrates and fats, as appropriate.

• Vitamins and minerals can only be declared if providing a significant amount (approximately one-sixth of the recommended daily amount).

• Fibre content – there are two methods available, the Englyst method (which measures non-starch polysaccharide) and the Association of Analytical Communities (AOAC) method, giving two different results. The UK has since adopted the AOAC method, which provides a higher estimate of fibre content because it measures a much wider range of dietary fibre constituents. In 2007, the European Union regulations stated that in order to be able to able to label food a ‘source of fibre’ the product has to contain at least 3 g per 100 g or at least 1.5 g fibre per 100 kcal.

• Salt – this is sometimes expressed as sodium content.

Dietary reference values

Dietary reference values (DRVs) provide information on the amount of different nutrients that are needed for maintaining health in different groups of people in the UK. They are estimated requirements for a population rather than exact recommendation for individuals, whose energy expenditure and levels of physical activity will vary ( Fig. 16.3 ) . Worldwide, there is broad agreement on DRVs based on data from the WHO, FAO and other expert committees of the United Nations. Many countries have produced their own dietary reference standards. From the 1960s, the UK used single figures for each nutrient, known as the recommended daily intake (RDI) or recommended daily allowance (RDA). However, it was found that there was a large potential for misuse and misinterpretation of these single reference points. In response to this, in 1991 the DRVs guidelines were produced. These were re-calculated in 2011 by the Scientific Advisory Committee on Nutrition (SACN), partly due to the advancement in techniques used to calculate energy expenditure and partly the fact there is a growing obesity epidemic in the UK. RDAs were replaced in the UK by three DRVs: reference nutrient intake (RNI), estimated average requirement (EAR) and lower reference nutrient intake (LRNI). The RNI (see Fig. 16.3 ) values are similar to the RDAs, and meet the nutrient needs of the vast majority (97%) of any healthy population. The RNI for different nutrients is set two standard deviations above the EAR, the amount of a nutrient that is needed daily on average in a large population of normal people. The LRNI is set two standard deviations below the EAR and represents a level of usual nutrient intake, which is not likely to be sufficient in more than 97% of people. Thus, an intake below the RNI does not suggest deficiency, but an intake below LRNI does.

Variations in nutritional requirements

Requirements for most nutrients vary with age and sex, and at times of physiological adaptation, e.g. during pregnancy, lactation and growth. Appropriate DRVs have thus been produced for these subgroups. In disease states such as infection, trauma, disorders of the gastrointestinal tract or metabolic abnormalities, requirements will vary. The DRVs for one nutrient assume that requirements for energy and all other nutrients are met.

Pregnancy

The energy demands of a pregnancy are usually estimated at approximately 323 MJ (77 000 kcal), although variations in activity levels account for major differences in the energy needs of individual women. Over the course of a full-term pregnancy, there should be an approximate weight gain of 12.5 kg, consisting of:

• 2.5 kg body weight

• 3.5 kg infant weight

• 6.5 kg placental weight.

During pregnancy, there are increased requirements for some, but not all, nutrients ( Clinical box 16.1 ). The diet must provide sufficient energy and nutrients to:

• provide extra growth of the breasts, uterus and placenta, and to meet the mother's needs

• meet the requirements of the growing foetus

• allow the mother to lay down stores of nutrients for lactation.

Pregnancy is often an ideal opportunity for clinicians to promote healthier eating for the benefit of the baby, immediate family and the wider community, although there has been little research into the effects of this form of intervention.

Clinical box 16.1

Nutrition during pregnancy

Nutritional requirements increase during pregnancy due to the requirements of the growing foetus, and the mother's body being prepared for parturition and lactation.

• Energy: there are wide variations between individuals. Minimum threshold for maternal weight gain is 6.8 kg. Additional 838 kJ (200 kcal)/day required in the third trimester. Eat according to appetite.

• Protein: an additional 6 g/day to 51 g RNI.

• Vitamins:

  • –

    Folate: poor folic acid status is associated with an increased risk of neural tube defects. In most developed countries, all women who are planning a pregnancy are recommended to consider folic acid dietary supplements and to try to include folate-rich foods and foods fortified with folic acid in their diet. Women who become pregnant should supplement their diet immediately (0.4 mg folic acid) until the 12th week of pregnancy.

  • –

    Vitamin A: an increment of 100 mg/day to 800 mg/day throughout pregnancy. High doses (> 1500 mg) are known to be teratogenic.

  • –

    Vitamin D: supplemented to achieve an intake of 10 mg/day.

  • –

    Vitamin C: increase by 10 mg/day to 50 mg/day in the third trimester.

  • –

    Iron: 14.8 g/day, with no recommended increase in pregnancy unless iron stores are inappropriately low at the beginning of pregnancy.

Conditions that affect nutrition during pregnancy are:

• Nausea and vomiting

• Hyperemesis gravidarum

• Cravings, aversions and pica

• Heartburn

• Constipation.

Food intake

Detailed assessment of dietary intake is the province of the fully trained dietitian. However, a simple dietary history is often useful to doctors and other clinicians. For example, the number of meals and the quantity, content and variety of snacks consumed can give clues to whether intake is a factor for weight change. Basic enquiries into diet and the timing of meals and snacks can be usefully incorporated into routine questions about lifestyle. The relation of gastrointestinal symptoms with food intake can be of great clinical importance.

Detailed dietary assessment

A full quantitative dietary assessment is time consuming, and depending on the method used, often subjective. Table 16.2 summarises the most commonly used methods of recording intake. Misreporting is common as people can feel guilty or embarrassed about aspects of their diet. In addition, food choices may be influenced when intake is recorded by the patient. All food intake varies by day of the week and season.

Table 16.2

Methods for recording food intake

Type	Definition	Uses	Disadvantages
Weighed food record	Record with weights of portions served, and plate waste	When a quantified measure of nutrient intake is required, e.g. in specialised research studies	Not all foods fully weighed, as logistically this can be difficult and can lead to poor compliance
Unweighed food record	Estimated record using portions described in household measures (spoon, cups, etc.)	Semiquantitative measure used to identify meal patterns, food choices, e.g. associations between food and symptoms	Can be hard to quantify specific nutrient intakes
24-hour recall	The respondent is asked to recall all food eaten within the past 24 hours	As a quick assessment of food choices/meal patterns	Past 24 hours may not be representative of usual intake
Food frequency questionnaire	A questionnaire consisting of a list of foods. The respondent has to say how often each food is eaten – per day/week/month	For identifying foods eaten less often, which may be of special interest and not included in short-term food records, e.g. when trying to identify certain nutrients consumed over a larger period of time	May not be a good assessment of total diet
Diet history	Respondent is asked detailed questions about usual intake. The aim is to get a comprehensive 7-day estimate of intake	Method used by the majority of dietitians in clinical practice for fast assessment and immediate advice	Information can be difficult to obtain, and often misreported

Once completed, a dietary record can be analysed into its constituent nutrients by using food composition tables or computer packages based on them. Information on dietary balance, deficiencies and surpluses, specific nutrients and compliance with previously given advice can be obtained from such programs. For example, comparisons can be made with age- and gender-specific DRVs.

‘Usual weight’ and weight loss/gain

‘Usual weight’ may be constant or variable. If variable, the weight at which the patient feels best should be identified, as well as the weight immediately before illness or when weight loss commenced. Previous records of body weight are helpful. Usual weight allows estimation of percentage weight loss once current weight has been measured:

Percentage weight gain is calculated by reversing previous and current weights. The timing of the weight change should be noted; whether the weight loss is intentional or unintentional is important:

• In intentional weight loss produced by well-designed dieting, the lean body mass component may represent only 25% of the decrease in weight

• In disease-related unintentional weight loss , 60% or more of the loss may be lean.

Weight measurements are distorted by fluid retention or loss. However, day-to-day weight comparisons may provide useful clinical information in assessing changes in hydration.

Body mass index

To be clinically informative, body weight needs to be expressed as a function of height. The most widely used stature-adjusted weight index is the body mass index (BMI) otherwise known as the Quetelet index (QI).

BMI (QI) is useful for identifying underweight and overweight individuals ( Table 16.3 ). BMI, like body weight itself, does not differentiate between fat or lean body mass. Oedema and ascites may result in a higher BMI and an overestimate of muscle mass, whereas heavily muscled individuals, such as body builders, may have a BMI that suggests that they are ‘overweight’.

Table 16.3

The international classification of underweight, overweight and obese adults according to BMI

Adapted from WHO (1995, 2000, 2004).

Classification	BMI (kg/m 2 )
	Principal cut-off points	Additional cut-off points
Underweight	< 18.50	< 18.50
Severe thinness	< 16.00	< 16.00
Moderate thinness	16.00–16.99	16.00–16.99
Mild thinness	17.00–18.49	17.00–18.49
Normal range	18.50–24.99	18.50–22.99
		23.00–24.99
Overweight	≥ 25.00	≥ 25.00
Pre-obese	25.00–29.99	25.00–27.49
		27.50–29.99
Obese	≥ 30.00	≥ 30.00
Obese class I	30.00–34.99	30.00–32.49
		32.50–34.99
Obese class II	35.00–39.99	35.00–37.49
		37.50–39.99
Obese class III	≥ 40.00	> 40.00

BMI values, being ratios, are the same for males and females, and vary with age. Overweight and obesity may impair health, but the degrees of excessive fat accumulation vary between populations. Therefore, the health risk associated with increasing BMI differs for different populations.

It is important to be aware that, although a range of values is given for a healthy BMI, there may be an increased risk of disease at the upper limit of that range. For example, the risk of type 2 diabetes increases progressively over a BMI of 23 kg/m ² , which is within the normal range (18.5 to 24.99 kg/m ² ). One should also take into account racial diversity, which is reflected in alternative ranges of healthy BMIs suggested for different countries or ethnic groups. For example, south Asians are more at risk of developing type 2 diabetes at a relatively lower BMI.

Estimating body fat

There are several methods of estimating body fat, which range from simple to more complex.

One commonly employed is anthropometry, where, by using simple tools, the percentage of body fat can be estimated by measurements taken at selected anatomical sites where fat is deposited:

• Skinfold thickness

• Arm circumference

• Waist circumference and waist/hip ratio.

Plasma proteins

Serum albumin is often incorrectly used as an indicator of nutritional status, with levels often remaining normal in undernutrition that is uncomplicated by disease. The decrease in serum albumin concentration during infection, cancer, burns and after trauma or surgery is related primarily to increased vascular permeability. Although undernutrition may exacerbate disease-related hypoalbuminaemia, albumin concentration primarily reflects a disease process, and it is better considered as an ‘index of disease severity’ rather than a nutritional indicator. Serum albumin can also be depressed by dilution during refeeding or excessive rehydration. It should be interpreted in combination with some other estimate of the acute-phase response, such as C-reactive protein or the erythrocyte sedimentation rate.

The same problems apply to other plasma proteins that are used as nutritional indicators, such as pre-albumin, transferrin and retinol-binding protein. However, these may be more sensitive as nutritional indicators because they have a shorter half-life in the circulation and can respond to dietary change more quickly.

Vitamin status

Vitamin deficiencies can be detected either by biochemical assays or by physical symptoms (see later). The detailed assessment of vitamin status is beyond the scope of this chapter. The relatively common presentation of macrocytic anaemias necessitates vitamin B ₁₂ and folate assays, but other vitamin deficiencies are unmeasured and often overlooked. Specific deficiency syndromes are outlined later.

Muscle strength

Studies have shown that malnutrition leads to impaired muscle strength, and nutritional support may rectify this before improvements in weight are seen.

Immunological skin testing

Adequate nutrition is essential for the maintenance of a normal immune system. A reduced blood total lymphocyte count may be indicative of protein calorie malnutrition. Delayed hypersensitivity is particularly affected by undernutrition.

Malnutrition screening tools

Research has shown that not only are a significant number of patients already malnourished on entry to hospital, but that hospital admissions are also often associated with a deterioration in nutritional state. The causes of this are invariably multifactorial, but the associated effects on morbidity and mortality are reflected in the high rates of readmission, lengthier hospital stays, susceptibility to infection and impaired wound healing in such patients. This has prompted some countries to develop national guidelines that recommend mandatory assessment of the nutritional status of all patients in hospital, as well as those who are at risk in the community, in order to identify those who may require nutritional support. In the UK, these have been developed by the National Institute for Health and Care Excellence (NICE). Many hospitals and other healthcare settings will have their own screening tools that combine features from the history and clinical examination, which are then ranked and combined to produce a score indicating malnutrition risk. In the UK, the Malnutrition Universal Screening Tool (MUST) is a five-step process based on BMI and weight loss designed to identify patients who are at risk of malnutrition or obesity, and includes management guidelines. In other parts of Europe, the nutritional risk screening (NRS-2002) is often employed, whereas the Mini Nutritional Assessment (MNA) and more complex Subjective Global Assessment (SGA) are used more commonly in the United States and Canada.

Conversion of macronutrients to energy

After absorption, macronutrients may pass through a number of different pathways of metabolism, shown in Fig. 16.4 , but ultimately the energy comes from the tricarboxylic acid (TCA) cycle and the mitochondrial process of oxidative phosphorylation (see in detail in Ch. 3 ).

Energy balance

Positive energy balance results in weight gain and the deposition of fat and glycogen, whereas a negative energy balance leads to weight loss and the depletion of glycogen and fat stores and ultimately muscle loss. The chemical energy content of food (measured in calories or joules) is the amount of energy that would be released from food if it was burned in oxygen in a fixed volume. This can be undertaken experimentally using a bomb calorimeter, which measures the heat produced per unit of food.

In healthy people, most of the energy in food is absorbed – approximately 97% of the energy in carbohydrate, 95% in fat and 92% in protein. Less energy is absorbed from protein because nitrogen is metabolised to urea and not fully oxidised, so that some of the energy from protein is not available to the body (see Ch. 3 ).

Total energy expenditure and the effect of physical activity

The total amount of energy used up in a day will depend on the individual's BMR, the nature of their occupation (whether sedentary or labour intensive), and the amount of physical activity undertaken in leisure and the pursuit of sports. The heat derived from food is not measured separately, but is included in measurements or estimations of energy expenditure.

Energy expenditure during daily living

Daily energy output for the activities of daily living can be estimated from the BMR and the individual's physical activity level (PAL), an index derived from experimental studies of energy expenditure for physical activity over 24 hours. Energy expenditure during activities of daily living is best measured by the doubly labelled water method, which allows measurements to be made over periods of days or weeks. PAL is expressed as a ratio of TEE and the REE (BMR). Total daily energy requirement can be calculated from a table of PAL, calibrated for the subject's leisure and work occupation, which provides a multiple by which the estimated BMR can be multiplied. For any one individual, these values are obtained from reference tables ( Table 16.5 ). The most commonly used units are kcal/24 h or kJ/24 h.

Table 16.5

Physical activity levels (PALs)

Non-occupational activity	Occupational activity
	Light		Moderate		Moderate/heavy
	M	F	M	F	M	F
Non-active	1.4	1.4	1.6	1.5	1.7	1.5
Moderately active	1.5	1.5	1.7	1.6	1.8	1.6
Very active	1.6	1.6	1.8	1.7	1.9	1.7

Department of Health 1991 Dietary reference values for food energy and nutrients for the United Kingdom. HMSO, London (Report on Health and Social Subjects, No. 41).

An EAR for energy can be calculated by multiplying the BMR by the appropriate PAL (see Table 16.5 ). The PAL index takes into consideration occupational as well as non-occupational activities because an individual with a sedentary occupation may undertake a lot of non-occupational activity, and vice versa. Physical activity makes a variable contribution to the TEE, which, over average 24-hour periods, is nearly always less than the BMR.

An individual at rest would be using energy for maintaining BMR only, i.e. a PAL of 1. Many people in the developed world have sedentary occupations (light activity) and are non-active, or only moderately active, outside work. From the corresponding PAL of 1.4 and 1.5 (see Table 16.5 ), it can be seen that their energy consumption is mainly due to BMR; only approximately a third of it (0.4–0.5) is due to physical activity. For example, for a woman who has a BMR of 6000 kJ, has a sedentary occupation and is moderately active outside of work, the total daily energy output is:

$\begin{array}{c}6000\text{kJ}\times 1.5=9000\text{kJ}\\ \left(4.2\text{kJ is equivalent to}1\text{kcal}\right)\end{array}$

Estimates of energy consumption for different types of activity

More accurate estimates of energy consumption during a 24-hour period can be made by keeping a diary of each activity, then calculating the total by adding all the different components. The energy used during each activity is calculated by reference to physical activity ratios (PARs) for different activities. PAR is an index of the energy expenditure for the duration of a particular activity compared with a reference activity, such as BMR, expressed as the estimated energy cost per minute for the specific activity relative to the measured energy cost per minute for the reference activity. This index is used to compare the energy consumption of various activities by different people ( Table 16.6 ).

Table 16.6

Physical activity ratios (PARs) for different types of activity

	PAR	Example activity
PAR 1.2 (range 1.0–1.4)	Lying at rest	Reading
	Sitting at rest	Watching television, reading, eating
	Standing at rest
PAR 1.6 (range 1.5–1.8)	Sitting	Sewing, playing piano, driving
	Standing	Light kitchen work, ironing, office or laboratory work
PAR 2.1 (range 1.9–2.4)	Standing	Household chores, cooking
PAR 2.8 (range 2.5–3.3)	Standing	Vacuuming, making beds, showering
	Walking	3–4 km/h, cricket
	Industrial	Painting and decorating, machine tool, tailoring
PAR 3.7 (range 3.4–4.4)	Standing	Gardening, sailing
	Walking	4–6 km/h, golf
	Industrial	Motor vehicle repairs, bricklaying
PAR 4.8 (range 4.4–5.9)	Standing	Chopping wood, heavy gardening, volleyball
	Walking	6–7 km/h
	Exercise	Moderate swimming, gentle cycling, slow jogging
	Occupational	Labouring, digging/shovelling, felling trees
PAR 6.9 (range 6.0–7.9)	Walking	Uphill with load, cross-country, climbing stairs
	Exercise	Average jogging, cycling
	Sports	Football, tennis, more energetic swimming, skiing

Energy expenditure during exercise

Energy needs during exercise vary depending on whether it is intense, over a short period (e.g. 100 m sprint), or sustained endurance exercise, such as running a marathon ( Clinical box 16.2 ).

Clinical box 16.2

Energy needs for sport: advice for sportsmen and sportswomen for optimising performance

The advice on energy intake is aimed at enabling individuals to:

• Compensate for the high energy consumption produced by training and competition to maintain an optimal body weight (water, protein and fat)

• Ensure that the muscles and the liver contain plenty of stored glycogen prior to the event

• Replace glycogen quickly and optimally after sport or between events

• Maintain hydration during the sporting activity and salt replacement during prolonged endurance exercise.

Anaerobic carbohydrate metabolism

During short bursts of intense activity (e.g. sprinting, weight lifting), close to maximum oxygen consumption ( V O _2max ) takes place when the exercising muscles depend on their own individual stores of adenosine triphosphate (ATP), supported by glucose from the muscle's own store of glycogen. This allows for brief periods when energy consumption is substantially greater than can be supplied by circulating substrates and oxygen. This is called ‘anaerobic’ metabolism. It builds up lactate and an oxygen debt, which have to be compensated for later. Lactate is recycled to the liver for gluconeogenesis (Cori cycle) (see Ch. 3 ).

Aerobic carbohydrate metabolism

During more prolonged exercise, ‘aerobic’ metabolism takes place, in which muscle stores of ATP run out very quickly if they cannot be replenished. Energy during prolonged exercise can be provided by:

• The exercising muscle's glycogen stores

• Circulating energy substrate – glucose derived from hepatic glycogenolysis and gluconeogenesis

• Fatty acids derived from adipose tissue.

Training increases the capacity of the muscle mitochondria to oxidise circulating substrate, especially fatty acids, to produce ATP (see later, TCA cycle). This delays the time at which the relevant muscle's glycogen runs out and the athlete becomes especially fatigued (‘hits the wall’).

Nitrogen balance and protein requirements

Nitrogen balance is the difference between the amount of nitrogen that is ingested and the amount lost from the body. It indicates whether the body is anabolic or catabolic in terms of net protein metabolism: whether the lean tissue is increasing (positive nitrogen balance) or decreasing (negative nitrogen balance). Nitrogen is ingested in the form of dietary proteins, which are metabolised in the liver and excreted, mainly as urea, in the urine.

Dietary nitrogen

Nitrogen makes up approximately 16% of the weight of most proteins, i.e. 6.25 g protein contains 1 g nitrogen. Table 16.7 shows how a (numerically convenient) intake of 62.5 g protein, which equates with 10 g nitrogen, is balanced quantitatively by nitrogen excretion. Healthy adults have a net zero nitrogen balance, with ingestion of food by day balancing losses of nitrogen by day and night. Nitrogen balance is positive during growth, weight regain and pregnancy, and negative during starvation, protein deprivation, nutrient imbalance, trauma and sepsis.

Table 16.7

Adult nitrogen balance

Nitrogen intake (diet)	Nitrogen output (excretion)
62.5 g protein	Urine	8.50 g (7 g as urea)
	Faeces	0.75 g
	Other	0.75 g
	Total	10.0 g

In clinical practice, true nitrogen balance is seldom assessed. However, it should be remembered that, whereas in the normal individual a high nitrogen intake is balanced by a higher resulting output, it may not be possible, or indeed desirable, to achieve such balance in a patient in a catabolic state, who is losing excessive amounts of protein due to sepsis or trauma, even with significantly increased nitrogen intake.

Protein requirements

A positive nitrogen balance is seen during growth (nitrogen intake exceeds excretion), and sufficient nitrogen intake is required for cell renewal and to replace nitrogen excretion in adults. Adults in the developed world tend to eat more protein than they need: often more than the RNI of approximately 45 g/day for a non-pregnant woman and 55 g/day for a man.

Essential and non-essential amino acids

Twenty amino acids are needed for the manufacture of proteins in humans. These are traditionally categorised into essential/indispensible and non-essential/dispensible, although it should be noted that in metabolic terms there is an essential need for all the amino acids, as all are required within metabolic pathways. The essential amino acids cannot be synthesised endogenously and thus must be taken from the diet. Some amino acids are ‘conditionally’ essential; their rate of synthesis may not be sufficient to meet demand under all conditions and so they may need to be taken by the diet. Non-essential amino acids are those that can be synthesised from other amino acids or precursors. These are listed in Table 16.8 .

Table 16.8

Classification of amino acids

Essential	Non-essential	Conditionally essential
Isoleucine	Alanine	Arginine
Leucine	Aspartic acid	Glutamine
Valine	Asparagine	Histidine
Lysine	Cysteine
Methionine	Glutamic acid
Threonine	Glycine
Phenylalanine	Proline
Tryptophan	Serine
	Tyrosine

Obligatory nitrogen loss

Obligatory nitrogen loss is the amount of nitrogen excreted when protein is excluded from a diet otherwise adequate in energy, electrolytes, minerals, vitamins and trace elements. In this highly artificial situation, the daily excretion of nitrogen in the urine and faeces declines over a few days to a minimum ( Fig. 16.5 ) .

Minimum nitrogen requirement

In the absence of growth, nitrogen requirement is estimated by summing the obligatory loss in urine to faecal and other (e.g. skin, sweat) excretions on a protein-free diet (the so-called factorial method). However, an otherwise adequate diet providing only this amount of nitrogen (even as high-quality or first-class protein) does not achieve zero balance; the balance remains slightly negative because ureagenesis increases. A better way of finding minimum requirements in adults is by balance studies in which high-quality protein is gradually added to an otherwise complete diet until zero balance is obtained. In children, growth rates must be taken into account. Adults can maintain nitrogen balance on 96 mg N/kg per day.

Energy and protein metabolism during fasting and feeding

In healthy people, intracellular metabolism to produce energy is regulated by hormones (see Ch. 3 ). During the fed state, energy stores are laid down for use during periods of fasting ( Table 16.9 ). It is normal to fast overnight or for short periods during the day, but the body adapts if longer periods of fasting occur. The hormones insulin, glucagon, epinephrine (adrenaline), cortisol and growth hormone are involved in the regulation of energy metabolism, exerting short-term effects on the direction of metabolic pathways ( Information box 16.1 , Fig. 16.6 ; see also Ch. 3 ).

Table 16.9

Fuel stores in an average person

Adapted from Geissler C, Powers HJ (eds) 2005 Human nutrition, 11th edn. Elsevier, Edinburgh.

Fuel source	In weight (g)	In energy (kJ)
Fat
Plasma free fatty acids	0.4	16
Plasma triacylglycerols	4.0	156
Intramyocellular triacylglycerol	300	11 700
Adipose tissue	12 000	468 000
Carbohydrate
Plasma glucose	20	360
Liver glycogen	100	1800
Muscle glycogen	350	6300
Whole body protein	10 000	168 000

Note: The principal component of body weight (water) provides no energy. Protein is structural and therefore not all is available for energy production. Glycogen and protein in the body are in the hydrated state and so weigh much more, kilojoule for kilojoule, than fat, which is stored in adipose tissue. Adipose tissue contains relatively little water.

Information box 16.1

Effect of insulin in the fed and fasted states

During the fed state, the active metabolic pathways are for fuel breakdown, storage of excess fuel through glycogen and lipid synthesis, and protein synthesis (anabolism) (see also Ch. 3 ). These processes are induced by insulin, an anabolic hormone, to:

• Increase glycogen synthesis in the liver and muscle

• Increase hepatic glycolysis

• Increase glucose uptake into muscle

• Increase lipogenesis and decrease lipolysis

• Increase cellular uptake of amino acids and net protein synthesis.

In fasting, which can begin a few hours after the last meal, the direction of the metabolic pathways is reversed to break down stored fuels to produce energy. Protein synthesis also slows down. The level of circulating insulin falls. (In the stress of disease or trauma, the action of insulin is opposed by increased levels of glucagon, epinephrine, cortisol and growth hormone.) Glycogenolysis, lipolysis, ketogenesis and gluconeogenesis are promoted.

The anabolic, fed, high-insulin state results in net storage of protein and glycogen. The catabolic, fasted, low-insulin state results in mobilisation of, firstly, glycogen for maintenance of blood glucose, and, subsequently, amino acids (especially 3C alanine) as substrate to make 6C glucose (gluconeogenesis–alanine cycle). 5C glutamine is an amino acid and is metabolised by rapidly dividing cells, for example enterocytes and lymphocytes, to 3C alanine which is then returns to the liver. During brisk exercise, when a low-insulin state prevails, the exercising muscles take up glucose, which may not be fully oxidised. Lactate is produced and recycled, after anaerobic glycolysis, back to the liver for gluconeogenesis (Cori cycle) (see Ch. 3 .)

Fed state

When nutrients are abundant, metabolic processes are geared to the catabolism of macronutrients and anabolism of the excess products for storage against lean times.

Absorbed carbohydrate in the fed state

After a meal, blood glucose rises, as shown in the blood glucose response curves in Fig. 16.7 . Some foods produce a blood glucose response very similar to that of glucose, the reference food; others produce a much flatter curve. Glucose is made available for:

• Metabolism

• Storage as glycogen (principally in muscle and liver)

• In more extreme excess, lipogenesis.

Many physical and chemical characteristics of carbohydrates affect how quickly they are absorbed and are reflected in how quickly blood sugar rises and falls after they are eaten. The glycaemic index (GI) describes this response in relation to glucose (see Fig. 16.7 ), and foods can be classified as having low, intermediate or high GI ( Table 16.10 ). This is used in the management of diabetes; low GI foods are recommended as an aid to restricting glucose intake. In the UK, low GI foods are recommended to the general population as part of a balanced diet. However, estimating the total GI of a meal is not practical in clinical situations because there are many factors that affect the GI, including:

• Pectin to amylopectin ratio in the food (mainly fruit)

• Degree of ripeness (fruit) and method of preparation (e.g. mashing increases the GI of potatoes)

• Size of the meal

• Addition of fat.

Table 16.10

Classification of foods by glycaemic index

Glycaemic index	Foods
High (70–100)	Bread (white or wholemeal), glucose, fruit juices, honey, mashed potatoes
Intermediate (56–69)	Granary bread, rice
Low (< 55)	Pulses, beans, peas, legumes, oat and oat-based cereals, pasta, raw fruit

Absorbed fat in the fed state

Dietary fat is approximately 95% triacylglycerol (TAG) (also known as triglyceride), with cholesterol and phospholipids making up the other main components. Dietary fats in the form of TAG are digested by pancreatic enzymes in the intestine to form free fatty acids and 2-monoacylglycerol (MAG), which are absorbed by the enterocytes (see Ch. 15 ). The enterocytes re-esterify some of the free fatty acids and MAG to synthesise TAGs. Chylomicrons are then assembled from TAGs, cholesterol, apoproteins and phospholipids. Most TAGs enter the systemic circulation as chylomicrons, via the thoracic duct. Medium- and short-chain fatty acids pass directly into the liver via the portal vein. Cholesterol (like bile acids) is absorbed in the last 100 cm or so of the terminal ileum.

In the fed state, the excess of circulating TAG is stored in adipose tissue whose lipid content reflects dietary fatty acid composition. When there is excess carbohydrate intake, it is principally stored as glycogen. Biochemically, dietary carbohydrate can be, but is not usually, converted to fatty acids in the liver and stored as TAG in adipose tissue.

Protein in the fed state

During the fed state, rates of body protein synthesis exceed rates of protein breakdown back to free amino acids, and net protein accumulation (positive nitrogen balance) occurs. The digestion of protein takes place firstly in the stomach by denaturation by stomach acid, then secondly in the small intestine by the action of pancreatic proteases to form a mixture of free amino acids and small peptides, following which a series of carrier systems transport them into the gut cells where they enter the portal blood for transport to the liver. Some amino acids, e.g. glutamine, are metabolised in preference to glucose in the gut, mainly to alanine (see Ch. 3 ). Alanine can enter gluconeogenesis, or together with other amino acids, can be used for the synthesis of liver structural or export proteins. Final degradation of amino acids results in the formation of glucose or glycogen from the carbon skeleton, and urea from the amino groups. A relatively small proportion of ingested amino acids, particularly the branched-chain amino acids valine, leucine and isoleucine, leave the liver to circulate generally to be available for protein synthesis. The liver therefore acts to protect the rest of the body from sudden potentially toxic surges in free amino acids.

In healthy individuals who have adequate protein consumption, 24-hour dietary intake and excretion of nitrogen should be equal (nitrogen balance). This will include periods of positive nitrogen balance (during feeding), where the rate of protein synthesis is higher than protein catabolism, and periods of negative nitrogen balance (overnight usually), where the rate of synthesis is lower than protein catabolism.

Fasted state

When fasting, metabolic processes tend towards mobilisation of stored energy substrates to meet the energy requirements for maintaining essential biological functions. Metabolic pathways are not independent and in times of substrate deficit, the body has the ability to metabolise its stored energy substrates for energy ( Fig. 16.8 ; Information box 16.2 ) (see Ch. 3 ).

Information box 16.2

Metabolism of stored energy substrates in the fasted state

During fasting:

• The carbon chains of some (glucogenic) amino acids, particularly alanine, can be converted to glucose.

• Fatty acids cannot be converted to glucose or amino acids (only the glycerol component can be a small contributor to glucose).

• Fatty acids can only be oxidised via acetyl-CoA entering the tricarboxylic acid (TCA) cycle if there is plentiful oxaloacetate from glucose or glycogen metabolism.

• Deficiency of oxaloacetate results in acetyl groups forming keto acids, which can be, and are, metabolised during prolonged fasting or starvation. In starvation, as the brain switches from metabolising glucose (derived at first from glycogen and subsequently from protein/amino acids) to keto acids (derived from fat), it reduces the need for gluconeogenesis from amino acids and therefore ‘spares protein’.

The need for glucose in the fasted state

During fasting, and after all the glucose from a meal has been metabolised, blood glucose is maintained at a relatively constant ‘post-absorptive’ level by:

• Drawing on reserves of glycogen in the liver, i.e. glucose is produced via glycogenolysis (see Ch. 3 )

• Gluconeogenesis , when glucose is synthesised from lactate or non-carbohydrate (mainly protein) sources in the body (see Ch. 3 ).

The main stores for glycogen are in the liver and muscle. Hepatic glycogenolysis provides an almost immediate source of glucose during short-term fasting (e.g. overnight) for maintaining normal blood glucose concentration. The hormone glucagon activates hepatic glycogenolysis. Skeletal muscle glycogen cannot leave the muscle, so muscle glycogenolysis (activated by epinephrine) does not increase blood glucose and can only meet the energy requirements for muscle contraction during exercise (see Ch. 3 ).

Glucose from hepatic glycogenolysis is sufficient only for between 12 and 24 hours and cannot replace all the glucose needed for essential functions. To meet all the requirements, as hepatic glycogen depletes, gluconeogenesis in the liver and kidneys becomes important. Non-carbohydrate substrates for gluconeogenesis include (see Ch. 3 ):

• Lactate – from anaerobic glycolysis in red blood cells and from active skeletal muscle. Starting with lactate, gluconeogenesis is conceptually the reverse of anaerobic glycolysis, though there are slight differences in the pathway.

• Glycerol from fat metabolism – TAGs in adipose tissue are broken down to glycerol and free fatty acids by lipolysis (see Ch. 3 ). These fatty acids cannot be made into glucose. The glycerol component diffuses into the bloodstream to be reconverted to glucose in the liver and kidneys – a minor supply quantitatively.

• Amino acids from protein muscle breakdown – the main amino acids used in gluconeogenesis are alanine and glutamine, from muscle protein hydrolysis.

With prolonged fasting, the body minimises the drain on structural proteins by reducing the need for glucose and therefore gluconeogenesis from protein. This is achieved by muscles using fat for fuel, especially ketones (see later), and the brain adapting to using more ketone bodies.

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