Category Archives: Nutrition

Alcohol

Alcohol is a popular ‘nutrient’ consumed in large quantities all over the world. In many countries, alcohol consumption is becoming a major problem.
Ethanol (ethyl alcohol) is oxidized in the following steps (Information box 3.4) to acetaldehyde.
1 Acetaldehyde is then converted to acetate mainly in the liver mitochondria.

2 Acetate is released into the blood and oxidized by peripheral tissues to carbon dioxide, fatty acids and water. Alcohol dehydrogenases are found in many tissues and it has been recently suggested that enzymes present in the gastric mucosa may contribute substantially to ethanol  metabolism.
Ethanol itself produces 7 kcal s’ (29.3 kJ g-‘), but many alcoholic drinks also contain sugar, which increases their calorific value. For example, one pint of beer provides 250 kcal (1045 kJ). Therefore, the heavy drinker will be unable to lose weight if he or she continues to drink.

Measures of alcohol.

Measures of alcohol.

Effects of excess alcohol consumption

Excess consumption of alcohol leads to two major problems, both of which can be present in the same patient:

• Alcohol dependence syndrome
• Physical damage to various tissues
Each unit of alcohol, e.g. half a pint of beer, one single spirit, one small glass of wine, contains 8 g of ethanol. All the long-term effects of excess alcohol consumption are due to excess ethanol, irrespective of the type of alcoholic beverage, i.e. beer and spirits are no different  in their long-term effects.
Short-term effects, such as hangovers, depend on additional substances, particularly other alcohols such as isoamyl alcohol, which are known as congeners. Brandy and bourbon contain the highest percentage of congeners.
The amount of alcohol that produces damage varies and not everyone who drinks heavily will suffer physical damage. For example, only 20% of people who drink heavily develop cirrhosis of the liver. The effect of alcohol on different organs of the body is not the same; in some patients the liver is affected,in others the brain or muscle. The differences may be genetically determined

Guide to sensible drinking.

Guide to sensible drinking.

In general the effects of a given intake of alcohol seem to be worse in women. The following figures are for men and should be reduced by 50% for women.  For liver disease
• 160 g ethanol per day (20 single drinks) carnes a high risk
• 80 g ethanol per day (10 single drinks) carnes a medium risk
• 40 g ethanol per day (five single drinks) carries little risk. Heavy persistent drinkers for many years are at greater risk than heavy sporadic drinkers.
Susceptibility to damage of different organs is variable and the figures in Information box 3.5 are only a guide .

Physical effects of excess alcohol consumption.

Physical effects of excess alcohol consumption.

Alcohol consumption in pregnancy

Women are advised not to drink alcohol at all during pregnancy as even small amounts of alcohol consumed can lead to ‘small babies’.
The fetal alcohol syndrome is characterized by mental retardation, dysmorphic features and growth impairment; it occurs in fetuses of alcohol-dependent women.

Summary

A summary of the physical effects of alcohol is given. Details of these diseases are discussed in the relevant chapters. The effects of alcohol withdrawal.

Further reading

Dietary Reference Values for Food Energy and Nutrients for the United Kingdom. 41 DOH 1991. Report of the Panel on Dietary Reference Values of the Committee on Medical.

Aspects of Food Policy. London: HMSO.
Garrow GS (1988) Obesity and Related Disorders. Edinburgh:
Churchill Livingstone.
Truswell AS (1990) ABC of Nutrition, 2nd edn. London: British Medical Association.
Shilo ME, Young BR (1988) Modern Nutrition in Health and Disease, 7th edn. Philadelphia: Lea & Febiger.

Food allergy and food intolerance

Many patients ascribe their symptoms to food allergy or food sensitivity and there are a number of clinics in the UK where such sufferers are seen and started on exclusion diets. The scientific evidence that food does harm in most instances is incomplete, but certainly some evidence supports the following disease ‘entities’:
ACUTE HYPERSENSITIVITY. Some patients develop acute reactions to a particular food, e.g. urticaria, vomiting or diarrhoea after eating strawberries or shellfish. These reactions are presumably immunological hypersensitivity reactions mediated by IgE. This is usually not a clinical problem as the patients have already learned to avoid the suspected food.
ECZEMA AND ASTHMA-particularly in childrenhas been successfully treated by removal of eggs from the diet suggesting some form of food allergy.
RHINITIS AND ASTHMA have been produced by foods such as milk and chocolate, mainly in atopic subjects; again suggesting some food allergy.
CHRONIC URTICARIA. This has been successfully treated by exclusion diet.
MIGRAINE. In some subjects this seems to be triggered by foods such as chocolate, cheese and alcohol suggesting a trigger mechanism, although probably not a true allergic phenomenon.
In addition, some people suffer reactions due to:
• A constituent of food, e.g. the histamine in mackerel or canned food, or the tyramine in cheeses
• Chemical mediators released by food, e.g. histamine may be released by tomatoes or strawberries

• Toxic chemicals found in food, e.g. the food additive tartrazine
• An enzyme deficiency, e.g. milk-induced diarrhoea in alactasia or favabean-induced haemolytic anaemia in glucose-e-phosphate dehydrogenase deficiency Many other additives and compounds with certain E numbers have been implicated as causing reactions, but here the evidence is less than complete.
There is little or no evidence to suggest that diseases such as arthritis, behaviour and affective disorders, irritable bowel syndrome and Crohn’s disease are due to food ingestion.
Multiple vague symptoms such as tiredness or malaise  are also not due to food allergy. Most of the patients in this group are suffering from a psychiatric disorder.

The main pathways of ethanol oxidization to acetaldehyde.

The main pathways of ethanol oxidization to acetaldehyde.

MANAGEMENT

A careful history may help to delineate the causative agent, particularly when the effects are immediate. Skin-prick testing with allergen and measurement in the serum of antigen or antibodies have not correlated with symptoms and are usually misleading. ‘Fringe’ techniques such as hair analysis, although widely advertised, are valueless and possibly fraudulent. Diagnostic exclusion diets are sometimes used, but these are time consuming, although can occasionally be of value in identifying a particular food causing problems.
DIETARY CHALLENGE is used when the food and the test is given sublingually or by inhalation to try andreproduce the symptoms.  Again this may be helpful in a few cases.
Most people who have acute reactions to food realize it and stop the food, and do not require medical attention. In the remainder of patients, a small minority seem to be helped by modifying their diet, but good scientific evidence to support these exclusion diets is non-existent.

Central venous catheter placement

A silicone catheter is placed into a central vein, usually using the infraclavicular approach to the subclavian vein. The skin-entry site should be dressed carefully and not disturbed unless there is a suggestion of catheter-related sepsis.
Complications of catheter placement include central vein thrombosis, pneumothorax and embolism, but the major problem is catheter-related sepsis. Organisms, mainly staphylococci, enter along the side of the catheter, leading to septicaemia. Sepsis can be prevented by careful and sterile placement of the catheter, by not removing the dressing over the catheter entry site, and by not giving other substances (e.g. blood products, antibiotics) via the central vein catheter.
Sepsis should be suspected if the patient develops fever and leucocytosis. In two-thirds of cases, organisms can be grown from the catheter tip. Treatment involves removal of the catheter and appropriate systemic antibiotics.

Nutrition

With TPN it is possible to provide sufficient nitrogen for protein synthesis and calories to meet energy requirements. Electrolytes, vitamins and trace elements are also necessary. All of these substances are infused simultaneously.

NITROGEN SOURCE. Synthetic L-amino acid solutions are used, which contain between 9 and 17 g of nitrogen per litre. Most patients require at least 14 g of nitrogen per day.
ENERGY SOURCE. This is mainly provided by glucose with additional calories provided by a fat emulsion. Fat infusions provide a greater number of calories in a smaller volume than can be provided by carbohydrate. They are not hypertonic and they also prevent essential  fatty acid deficiency.
Essential fatty acid deficiency has been reported in long-term parenteral nutritional regimens without fat emulsions. It causes a scaly skin, hair loss and a delay in healing.
The calorie-to-nitrogen ratio should be approximately (kcal : g) 150:1 (0.6 MJ per gram of protein).

ELECTROLYTES AND TRACE ELEMENTS

The electrolyte status should be monitored on a daily basis and electrolyte solutions given as appropriate. Water-soluble vitamins can be given daily but fat-soluble vitamins should be given weekly, as overdose can occur. A trace-metal solution is available for patients on longterm parenteral nutrition, but if the patient requires blood transfusions trace-metal supplements are not needed.

Administration

CENTRAL VENOUS TPN REGIMEN. Most hospitals now use 3-litre bags with the constituents being premixed under sterile conditions by the pharmacy. A standard parenteral nutrition regimen is given.
PERIPHERAL PARENTERAL NUTRITION. This is administered via 5-litre bags over 48 hours.
shows the composition which provides 12 g of nitrogen and 1500 non-protein calories in 24 hours. Complications
• Catheter-related (see above)
• Metabolic, e.g. hyperglycaemia-insulin therapy is usually necessary

• Electrolyte disturbances
• Hypercalcaemia
• Liver dysfunction

Central catheter placement for parenteral nutrition.

Central catheter placement for parenteral nutrition.

Daily dietary electrolytes and trace elements required for long-term maintenance.

Daily dietary electrolytes and trace elements
required for long-term maintenance.

MONITORING OF PATIENTS ON PARENTERAL NUTRITION.

Essential monitoring includes daily plasma electrolytes and weekly assessments of nutritional status (weight and skinfold thickness). Nitrogen balance should also be measured on a weekly basis. Home parenteral nutrition is occasionally required for patients with virtually  no small bowel.

Examples of total parenteral nutrition regimens.

Examples of total parenteral nutrition regimens.

Nutritional support in the hospital patient

Nutritional support is now recognized as being necessary in many hospitalized patients. The pathophysiology and hallmarks of malnutrition have been described earlier; here the forms of nutritional support that are available are discussed.

PRINCIPLES

Some form of nutritional supplementation is required in those patients who cannot eat, should not eat, will not eat or cannot eat enough. It is necessary to provide nutritional support for:
• All severely malnourished patients on admission to hospital
•Moderately malnourished patients who, because of their physical illness, are not expected to eat for 3- 5 days
• Normally nourished patients not expected to eat for 7- 10 days Enteral rather than parenteral nutrition should always be used if the gastrointestinal tract is functioning normally

Enteral feeding.

Enteral feeding.

ENTERAL FEEDING
Feeds can be given by:
• Mouth.
• Fine-bore nasogastric tube (commonest method).
• Percutaneous endoscopic gastrostomy; this is useful for patients who need enteral nutrition for a prolonged period, e.g. following a head injury with swallowing problems. A catheter is placed percutaneously into the stomach, which has been dilated with air via a gastroscope.

• Needle catheter jejunostomy. A fine catheter is inserted into the jejunum at laparotomy and brought out through the abdominal wall.

DIET FORMULATION 

A polymeric diet with whole-protein and fat can be used except in patients with severely impaired gastrointestinal function who may require predigested, i.e. elemental diet. In these patients, the nitrogen source is purified low molecular weight peptides or amino acid mixtures with sometimes the fat being given partly as medium chain triglycerides.

Standard enteric diet (2000-3000 kcal, approx. 12000 kl, per day).

Standard enteric diet (2000-3000 kcal, approx.
12000 kl, per day).

MANAGEMENT

The aim of any regimen is to achieve a positive nitrogen balance, which can usually be obtained by giving 3-5 g of nitrogen in excess of output. Nitrogen loss can be calculated using the formula:
Nz loss (g per 24 hours) = urinary urea (mmol per 24 hours) – 0.028 + 2 (the 2 representing non-urinary nitrogen excretion). Daily amounts of diet vary between 2 and 2.5 litres and the full amount can be started immediately. Hypercatabolic patients require a high supply of nitrogen (15 g per day) and often will not achieve positive nitrogen balance until the primary injury is resolved.
The success of enteral feeding depends on careful supervision of the patient with monitoring of weight, biochemistry and diet charts.
TOTAL PARENTERAL NUTRITION (TPN)
There are two approaches:
PLACEMENT OF CENTRAL VENOUS CATHETER. This has been the standard approach for many years because of the high incidence of thrombophlebitis in peripheral vems.
PERIPHERAL PARENTERAL NUTRITION. This is now being used with the realization that lower total energy requirements are adequate, i.e. 2000 kcal in 24 hours. Specially formulated mixtures for peripheral use are now available with a low osmolality and containing lipid emulsions. Heparin and corticosteroids are added to the infusion and local application of glyceryl trinitrate patches reduces the occurrence of thrombophlebitis and prolong catheter usage. Initially, peripheral parenteral nutrition is used (each catheter will last for about 5 days) allowing more time to consider the necessity for having to insert a central venous catheter.
TPN is much more complicated and potentially more dangerous than enteral nutrition. It should therefore not be used unless absolutely necessary. It is seldom necessary for periods of less than 10 days.

TREATMENT

This largely depends on a reduction in calorie intake. The commonest diets allow an intake of approximately 1000 kcal (4200 kJ) per day, although this may need to be nearer 1500 kcal (6300 kJ) per day for someone engaged in physical work. A diet that is too low in totalcalories will usually result in the patient cheating and keeping to the diet only for short periods. Patients must realize that prolonged dieting is necessary for large amounts of fat to be lost. Furthermore, a permanentchange in eating habits is required to maintain the new low weight. It is relatively easy for most patients to lose the first few kilograms, but long-term success in moderate obesity is poor, with an overall success rate of no more than 10-20%.

Conditions and complications associated with obesity.

Conditions and complications associated with
obesity.

The aim of any dietary regimen is to lose approximately I kg per week. Weight loss will be greater initially owing to accompanying protein and glycogen breakdown and consequent water loss. After 3-4 weeks, weight loss may be very small as only adipose tissue is broken down and there is no accompanying water loss. Patients must understand the principles of energy intake and expenditure and the best results are obtainedin educated, well-motivated patients. Constant supervision, either by a doctor, close relatives or through slimming  societies (e.g. WeightWatchers) helps to encourage compliance.
An increase in exercise will increase energy expenditure and should be encouraged, as long as there is no contraindication such as cardiovascular disease. Weight cannot be lost by exercise alone, as even a 15-min brisk daily walk will use less energy than is contained in a small slice of bread and butter.
The diet should contain adequate amounts of each nutrient; a diet of 1000 kcal (4200 kJ) per day should be made up of approximately 100 g of carbohydrate, 50 g of protein and 40 g of fat. The carbohydrate should be in the form of complex carbohydrates such as vegetables and fruit rather than simple sugars. Alcohol contains 7 kcal g-l and should be discouraged. It can be substituted for other foods in the diet, but it often reduces the willpower. With a varied diet, vitamins and minerals will be adequate and supplements are not necessary. A balanced diet, attractively presented, is of much greater value and safer than any of the slimming regimens often advertised in women’s magazines.
Most obese people oscillate in weight; they often regain the lost weight, but many manage to lose weight again. This ‘cycling’ in body weight may playa role in the development of coronary artery disease.

Drug therapy

Drugs can be used as an adjunct to the dietary regimen but they do not substitute for strict dieting. Amphetamine is addictive, although some less-stimulating derivativesare now available that produce anorexia. However, their use should be discouraged as they cause dependency and psychotic states. The most commonly used drugs are diethylproprion (75 mg daily) and fenfluramine. The latter differs in that it acts on the serotoninergic system rather than the catecholaminergic pathway, which is affected by the amphetamine derivatives. It can be given in doses up to 100 mg daily, but side-effects are frequent.frequent. None of the drugs should be given long-term; they should be withdrawn slowly.

Surgical treatment

Operations involving bypass of parts of the small intestine have fallen out of favour because of their side-effects and cannot now be recommended. Jejunoileal bypass was the commonest operation and involved the anastomosis of approximately 18 ern of jejunum to the terminal 18 cm of the ileum. Complications are chiefly those of intestinal resection (see p. 210). A fatty liver often occurs and in a few patients cirrhosis is seen. Three procedures are still performed in cases of severe morbid obesity:
WIRING THE JAWS to prevent eating and allow liquid feeds only. This can be used as a temporary measure but good dental hygiene is essential. Weight gain usually occurs after the wires have been removed, but this can be controlled by the use of a tight waist cord.
GASTRIC PLICATION, in which a small gastric pouch is created by stapling across the wall of the stomach. Good results are claimed without the side-effects of bypass operations.
GASTRIC BALLOON. Here a balloon is placed endoscopically inside the stomach and inflated. Its value has been over-exaggerated and complications include intestinal obstruction.

MORBIDITY AND MORTALITY

There is an increase in death in obese patients, mainly from diabetes, coronary heart disease and cerebrovascular disease. The greater the obesity the higher the morbidity  and mortality figures. For example, men who are 10%overweight have a l3% increased risk of death, whilst the increase in mortality for those 20% overweight is 25%. The rise is less in women. Weight reduction reduces this mortality and therefore should be strongly encouraged.

Obesity

Some degree of obesity is almost invariable in the Western World and almost all people develop some obesity as they get older. Obesity implies the excess storage of fat and this can most easily be detected by looking at the undressed patient.

BMI values for men and women.

BMI values for men and women.

Tables of desirable weights for a given height can be found in the Appendices: 10% greater than these desirable weights is described as overweight; 20% or more than the ideal weight as morbid obesity. Another way of classifying grades of obesity is the body mass index (BMI) Information box 3.3):
BMI = weight (kg)/(height in metres)”

CAUSES OF OBESITY

Most patients suffer from simple obesity, but in certain conditions obesity is an associated feature;
even in these situations, intake of calories must exceed expenditure. Hormonal imbalance is often incriminated in women, e.g. postmenopause or when taking contraceptive pills, but most weight gain in such cases is usually all and due to water retention.

SIMPLE OBESITY

Not all obese people eat more than the average, but all viously eat more than they need.

Conditions in which obesity is an associated

Conditions in which obesity is an associated

Suggested mechanisms

GENETIC AND ENVIRONMENTAL FACTORS. These have always been difficult to separate. However, refeeding experiments in both monozygotic and dizygotic twins, reared together or apart, suggest that genetic influences account for 70% of the differences in BMI later in life and that the childhood environment has little or no influence. These overfeeding experiments also showed that weight gain did not occur in all pairs of twins, suggesting that in some a facultative increase in thermogenesis occurred so that part of their extra dietary energy was expended inefficiently.
FOOD INTAKE. Many factors related to the home environment, e.g. finance and the availability of sweets and snacks, will affect food intake. Some patients eat more during periods of heavy exercise or during pregnancy and are unable to get back to their former eating habits. The increase in obesity in social class 5 can usually be related to the type of food consumed, i.e. food containing sugar and fat. The underlying mechanisms for controlling satiety are ill-understood; psychological factors and how food is presented may override complex biochemical interactions.
It has been shown that obese patients eat more than they admit to eating and over the years a very small daily excess can lead to a large accumulation of fat.
CONTROL OF APPETITE. This is complex and partially depends on external stimuli, such as the company, the type of food, the surroundings and the usual habitual behaviour.
Appetite is the desire to eat and this usually initiates food intake. Following a meal, satiation occurs. This depends on gastric and duodenal distension and the release of many substances peripherally and centrally. Cholecystokinin (CCK), bombesin and somatostatin are released from the small intestine and glucagon and insulin from the pancreas following a meal. All of these hormones have been implicated in the control of satiety. Centrally the hypothalamus, particularly the paraventricular nucleus, and the ventromedial wall of the hypothalamus are thought to be the main satiety centres. Numerous neurotransmitters, e.g. CCK, opioids, serotonin and corticotrophin-releasing hormone, playa role in the central control of satiation. In obesity, no single abnormality involving appetite control has been identified although the obese eat more than the non-obese.
ENERGY EXPENDITURE. Obese patients tend to expend more energy during physical activity as they have a larger mass to move. On the other hand, many obese patients decrease their amount of physical activity. The energy expended on walking at 3 miles per hour is only 15.5 k] min-I (3.7 kcal min-I) and therefore increasing exercise plays only a small part in losing weight. Nevertheless, as increased body fat develops insidiously over many years, any discrepancy in energy balance is important.

THERMOGENESIS. Brown adipose tissue in animals when stimulated by cold or food dissipates the energy derived from ingested food as heat. This can be a major component of overall energy balance and it has been suggested that this may also apply to humans. A defect in thermogenesis would explain why some obese patients require a very low calorie intake to maintain any weight loss achieved and gain weight easily after only small calorie increases. This mechanism may play some role in the development of obesity.

CLINICAL FEATURES

Most patients recognize their own problems, although often they are unaware of the main foods that cause obesity. Many symptoms are related to psychological problems,e.g. in women who cannot find fashionable clothes to wear. Social pressures are also important.
The degree of obesity is assessed by comparison with tables of ideal weight for height (see Appendices), the BMI and also by measuring skinfold thickness. This should be measured over the middle of the triceps muscle;  normal values are 20 mm in a man and 30 mm in a woman. The conditions and complications that are associated with obesity. The relationship between cardiovascular disease (hypertension or ischaemic heart disease), hyperlipidaemia, smoking, physical exercise and obesity is complex. Difficulties arise in interpreting mortality figures because of the number of factors involved. Many studies of obesity do not, for instance, differentiate between smokers and non-smokers or between the types of physical exercise that are taken. Many do not take into account the cuff-size artefact in the measurement of blood pressure; an artefact will occur if a large cuff is not used in patients with a large arm. Nevertheless, obesity almost certainly plays a part in all of these diseases and should be treated. The only exception is that stopping smoking, even if accompanied by weight gain, is more important than any of the other factors.

Nutrition and ageing

Many animal studies have shown that life expectancy can be extended by restricting food intake. It is, however, not known in humans whether the ageing process can be alteredby nutrition.

THE AGEING PROCESS

While wear and tear may playa role in ageing, it does not appear to be a sufficient explanation for the occurrence of ageing. A number of theories have been postulated.

PROGRAMMED AGEING. This theory suggests a predetermined, presumably genetic, age-related alteration in cellular function that leads to susceptibility to disease and death.
THE GENOMIC INSTABILITY THEORY suggests errors in genetic transcription and translation resulting in impaired protein synthesis and deterioration in cell function as age increases.
THE FREE RADICAL THEORY OF AGEING suggests that these highly reactive molecules are no longer metabolized rapidly so that accumulation occurs leading to irreversible cell damage.
RANDOM GENETIC ERRORS have also been implicated and an accumulation of errors over time is said to result in impaired protein synthesis. Several other mechanisms have been suggested, but it is still unclear whether there is one universal or several independent mechanisms involved.

NUTRITIONAL REQUIREMENTS IN THE ELDERLY

These are qualitatively similar to younger adults, but as energy expenditure is less, there is a lower energy requirement. However, maintaining physical activity is required for the overall health of the elderly. The daily energy requirements of the elderly have recently been set to be approximately 1.5 x BMR (age 60 and above, irrespective of age). The BMR is reduced due to a fall in the fat-free mass from an average of 60 to 50 kg in men and from 40 to 35 kg in women. The diet should contain the same proportion of nutrients and essential nutrients are still required.
NUTRITIONAL PROBLEMS are due to many factors, such as dental problems, lack of cooking skills, particularly in elderly widowers, depression and sometimes lack of motivation. Significant malnourishment in developed countries is usually secondary to social problems or disease. In the elderly who are institutionalized, vitamin D supplements may be required as often patients do not go into the sunlight.
Due to the high prevalence of osteoporosis in elderly people, daily calcium intake should be between 1 and 1.5 g.

Minerals

A number of minerals have been shown to be essential ill animals and an increasing number of deficiency syndromes are becoming recognized in humans. Longterm total parenteral nutrition allowed trace-element deficiency to be studied in controlled conditions; now trace elements are always added to long-term parenteral nutrition regimens. It is highly probable (but difficult to study because of multiple deficiencies) that trace-element deficiency is also an important accompaniment of all PEM states. Sodium, potassium, magnesium and chloride.

IRON 

The daily RNI for men is 160 urnol (8.7 mg) and for women 260 urnol (14.8 mg). Iron deficiency is common worldwide, affecting both developing and developed countries alike. It is particularly prevalent in women of a reproductive age. Dietary iron overload is seen in the South African Bantu men who cook and brew in iron pots.

COPPER

The daily RNI is 1.2 mg (19 urnol).

Deficiency

Menkes’ kinky hair syndrome is a rare condition due to malabsorption of copper. Infants with this sex-linked abnormality develop growth failure, mental retardation, bone lesions and brittle hair. Anaemia and neutropenia also occur. This condition, which serves as a model for copper deficiency, supports the idea that some of the clinical features seen in PEM are due to copper deficiency. Breast and cows’ milk are low in copper and supplementation is occasionally necessary when first treating PEM.

Toxicity

Copper toxicity occurs in Wilson’s

ZINC

The daily RNI is 9 mg (140 urnol). Zinc is involved in many metabolic pathways, often acting as a coenzyme; it is essential for the synthesis of RNA and DNA. It is widely available in food.

Deficiency

Acrodermatitis enteropathica is an inherited disorder due to malabsorption of zinc. Infants develop growth retardation, severe diarrhoea, hair loss and associated Candida and bacterial infection. Zinc supplement results in a complete cure. This condition provides a model for zinc deficiency. Deficiency probably plays a role in PEM.
Zinc levels have also been shown to be low in some patients with malabsorption, skin disease and AIDS, but the exact role of zinc in these situations is disputed. High zinc levels from water stored in galvanized containers interfere with iron and copper metabolism.

IODINE

The daily RNI is 140 ILgu.i umol). Iodine exists in foods as inorganic iodines which are efficiently absorbed.
Many mountainous areas throughout the world lack iodine in the soil and iodine deficiency is a WHO priority. Endemic goitre occurs in areas where the daily intake is below 70 ILg (p.803) and here 1-5% of babies are born with cretinism. In these areas iodized oil should be given intramuscularly to all reproductive women. In developed countries, salt is iodized and endemic goitre has disappeared

FLUORIDE

In areas where the level of fluoride is less than 1 p.p.m. in drinking water, dental caries is more prevalent. Fluoridation of the water reduces this. Excessive fluorine intake can result in fluorosis, in which there is infiltration of the enamel of the teeth with fluorine, producing pitting and discoloration.

SELENIUM

The daily RNI is 60 ILg (0.8 umol), Keshan disease is a selenium-responsive cardiomyopathy found in areas of China.

CALCIUM

The daily RNI is 700 mg (17.5 mmol).
This is found in many foods but particularly in milk. Its absorption from the gastrointestinal tract is vitamin D-dependent. Ninety-nine per cent of body calcium is in the skeleton. Increased calcium is required in pregnancy and lactation, when dietary intake must be increased. Calcium deficiency is usually due to vitamin D deficiency.

PHOSPHATE

The daily RNI is equivalent to calcium, i.e. 17.5 mmol. Phosphates are present in all natural foods and dietary deficiency has not been described. Patients taking large amounts of aluminium hydroxide can, however, develop phosphate deficiency owing to binding in the gut lumen. It can also be seen in total parenteral nutrition. Symptoms include anorexia, weakness and osteoporosis. Other trace elements of possible significance.

RIBOFLAVIN

Riboflavin is widely distributed throughout all plant and animal cells. Good sources are dairy products, offal and leafy vegetables. Riboflavin is not destroyed appreciably by cooking, but is destroyed by sunlight. Riboflavin is a flavoprotein that is a cofactor for many oxidative reactions in the cell.
Riboflavin deficiency, which is rare in developed countries, is virtually always accompanied by other deficiencies and many features previously attributed to riboflavin deficiency are probably due to multiple deficiencies:

• Angular stomatitis or cheilosis (fissuring at the corners of the mouth)
• A red, inflamed tongue
• Seborrhoeic dermatitis, particularly involving the face (around the nose) and the scrotum or vulva Riboflavin (5 mg) daily can be tried for the above conditions, usually given as vitamin B complex.

NIACIN

This is the generic name for the two chemical forms: nicotinic acid and nicotinamide, the latter being found in the two pyridine nucleotides, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Both act as hydrogen acceptors in many oxidative reactions and in their reduced forms (NADH and NADPH) act as hydrogen donors in reductive reactions. Many oxidative steps in the production of energy require NAD, and NADP is equally important in the hexose monophosphate shunt for the generation of NADPH, which is necessary for fatty-acid synthesis.

Niacin is found in many foodstuffs, including plants, meat (particularly offal) and fish. Niacin is lost by removing bran from cereals but is added to processed cereals and white bread in many countries. Niacin can be synthesized in humans from tryptophan, 60 mg of tryptophan being converted to I mg of niacin. The amount of niacin in food is given as the niacin equivalent which is equal to the amount of niacin plus one-sixtieth of the tryptophan content.

Pellagra

This is now rare and is found in people who virtually only eat maize, e.g. in parts of Africa. Maize contains niacin in the form of niacytin, which is biologically unavailable, and has a low content of tryptophan. Many of the features of pellagra can be explained purely by niacin deficiency; some, however, are probably due to multiple deficiencies, including proteins and other vitamins.

CLINICAL FEATURES

The classical features are of dermatitis, diarrhoea and dementia. Although this is an easily remembered triad, not all are always present and the mental changes are not a true dementia.

Dermatitis

Initially there is a redness of the skin in the areas exposed to sunlight. This is followed by cracks in the skin, with occasional ulceration. Chronic thickening, dryness andpigmentation develop. The lesions are always symmetrical and often affect the dorsal surfaces of the hands. The perianal skin and vulva are frequently involved. Casal’s necklace or collar is the term given to the skin lesion around the neck, which is confined to this area by the clothes worn.

Diarrhoea

This is often a feature but constipation is occasionally seen. Other gastrointestinal manifestations include painful red raw tongue, glossitis and angular stomatitis.Recurring mouth infections occur.

Dementia 

This occurs in chronic disease. In milder cases there are symptoms of depression, apathy and sometimes thought disorders. Tremor and an encephalopathy frequently occur. Hallucinations and acute psychosis are seen with more severe cases.
Pellagra may also occur:
THERAPY WITH ISONIAZID, as this can lead to a deficiency of vitamin B6, which is needed for the synthesis of nicotinamide from tryptophan; vitamin B6 is now given concomitantly with isoniazid
HARTNUP DISEASE, a rare inborn error whereby basic amino acids including tryptophan are not absorbed by the gut and there is also loss of this amino acid in the urine
GENERALIZED MALABSORPTION (rare)

ALCOHOL-DEPENDENT patients who do not eat
VERY LOW PROTEIN DIETS given for renal disease or taken as a food fad
CARCINOID SYNDROME and phaeochromocytoma, in which tryptophan metabolism is diverted away from the formation of nicotinamide to form amines

The oxidative pathway of tryptophan metabolism.

The oxidative pathway of
tryptophan metabolism.

DIAGNOSIS

In endemic areas this is based on the clinical features, remembering that other vitamin deficiencies can produce similar changes, e.g. angular stomatitis. Nicotinamide (approximately 300 mg daily by mouth) with a maintenance dose of 50 mg daily is given. Mostly, however, vitamin B complex is given, as other deficiencies are often present. An increase in the protein content of the diet and treatment of malnutrition and other vitamin deficiencies is essential. Mild cases respond well but dementia is often permanent.

VITAMIN B6

Vitamin B6 exists as pyridoxine, pyridoxal and pyridoxamine, and is found in plant and animal foodstuffs. Pyridoxal phosphate is involved in the metabolism of aminoacids. Dietary deficiency is extremely rare. Some drugs are antagonistic to B6, e.g. isoniazid, hydralazine and  penicillamine. The polyneuropathy occurring after isoniazid usually responds to vitamin B6. Sideroblastic anaemia occasionally responds to vitamin B6

Water-soluble vitamins

Water-soluble vitamins are non-toxic and relatively cheap and can therefore always be given in excess if a deficiency is possible. The daily requirements of water-soluble vitamins.

THIAMINE

Thiamine is a co-factor of many enzyme reactions, particularly in the glycolytic pathway. Body stores are small and signs of deficiency will quickly develop with an inadequate intake. Thiamine is found in many foodstuffs and deficiency is only seen:
• As beriberi, where the only food consumed is polished rice
• In chronic alcohol-dependent patients who are consuming virtually no food at all
• Rarely in starved patients, e.g. with carcinoma of the stomach; severe prolonged hyperemesis gravidarum, especially when treated by i.v. fluids alone

Beriberi

This is now confined to the poorest areas of South East Asia. It can be prevented by eating undermilled or parboiled rice, or by fortification of rice with thiamine. Probably the most important factor in the reduction of beriberi is the general increase in overall food consumption so that the staple diet is varied and contains legumes and pulses, which contain a large amount of thiamine. There are two main clinical types of beriberi, which, surprisingly, only rarely occur together.
DRY BERIBERI usually presents insidiously with a symmetrical polyneuropathy. The initial symptoms are heaviness and stiffness of the legs, followed by weakness, numbness, and pins and needles. The ankle jerk reflexes are lost and eventually all the signs of polyneuropathy that may involve the trunk and arms. Cerebral involvement occurs, producing the picture of the Wernicke-Korsakoff syndrome (p. 947). In endemic areas mild symptoms and signs may be present for years without unduly affecting the patient.
WET BERIBERI causes oedema. Initially this is of the legs, but it can extend to involve the whole body, with ascites and pleural effusions. The peripheral oedema may mask the accompanying features of dry beriberi. Thiamine deficiency results in inadequate metabolism of glucose and the accumulation of lactate and pyruvate, producing peripheral vasodilatation and eventually oedema. The heart muscle is also affected and heart failure occurs, causing a further increase in the oedema. Initially there are warm extremities, a full, fast, bounding pulse and a raised venous pressure (‘high output state’) but eventually heart failure advances and a poor cardiac output ensues. The electrocardiogram may show conduction defects.
INFANTILE BERIBERI occurs, usually acutely, in breastfed babies at approximately 3 months old. The mothers show no signs of thiamine deficiency but presumably their body stores must be virtually nil. The infant becomes anorexic, develops oedema and has some degree of aphonia. Tachycardia and tachypnoea develop and, unless treatment is instituted, death occurs quickly.

DIAGNOSIS

In endemic areas the diagnosis of beriberi should always be suspected and if in doubt treatment with thiamine should be instituted. A rapid disappearance of oedemaafter thiamine (50 mg i.m.) is diagnostic. Other causes of  oedema must be considered, e.g. renal or liver disease, and the polyneuropathy is indistinguishable from that due to other causes. The diagnosis is confirmed by measurement of transketolase activity in red cells. This enzyme is dependent on thiamine pyrophosphate (TPP). The assay is performed with and without added TPP; an increase in activity of 30% with TPP indicates deficiency.

TREATMENT

Thiamine 50 mg i.m. is given for 3 days, followed by 20 mg of thiamine daily by mouth. The response in wet beriberi occurs in hours, giving dramatic improvement, but n dry beriberi improvement is often slow to occur. In most cases all the B vitamins are given because of multiple deficiency. Infantile beriberi is treated by giving thiamine to the mother, which is then passed on to the infant via the breast milk.

Thiamine deficiency in patients with alcohol dependence

In the western hemisphere, this is the only major group to suffer from thiamine deficiency. Rarely they develop wet beriberi, which must be distinguished from alcoholic cardiomyopathy. More usually, however, thiamine deficiency presents with polyneuropathy or with the Wernicke- Korsakoff syndrome. This syndrome, which consists of dementia, ataxia, varying ophthalmoplegia and nystagmus (see p. 947), presents acutely and should be suspected in all heavy drinkers. If treated promptly, it is reversible, but if left, it becomes irreversible; it is a major cause of dementia in the USA. Urgent treatment with thiamine 50-100 mg i.m. or i.v. is given for 3 days, often combined with other vitamin B complex vitamins. Thiamine must always be given before any intravenous glucose infusion.