nutrition pdf - د. سعد

Nutrients

the

diet can be classified into ‘

macronutrients

’,

which are eaten in relatively large amounts to
provide fuel for energy, and ‘

micronutrients

’ (e.g.

vitaminsand minerals), which do not contribute to
energy balance but are required in small amounts
because they are not synthesised in the body.

Energy intake is determined by the ‘macronutrient’
content of food. Carbohydrates, fat, protein and alcohol
provide fuel for

oxidation in the mitochondria

generate
energy (as adenosine triphosphate (

ATP)

. The

energy provided by each of these elements differs:
•

carbohydrates

(16 kJ/g)

•

fat

(37 kJ/g)

•

protein

(17 kJ/g)

•

alcohol

(29 kJ/g).

Vitamins

are organic substances with key

roles in certain
metabolic pathways, and are categorised into
those that
are fat-soluble (vitamins A, D, E and K) and those
that
are water-soluble (vitamins of the B complex
group and
vitamin C).

Vitamin A (retinol)

Pre-formed retinol is found only in foods of animalorigin. Vitamin A can also be derived from

carotenes,

which are present

in green and coloured vegetables and some fruits

. Carotenes provide most of

the total

vitamin A in the UK, and constitute the only supply invegans. Retinol is converted to several

other important

molecules:

•

11-cis retinaldehyde

is part of the photoreceptor complex in rods of the retina

•

Retinoic acid induces

differentiation of epithelial

cells by binding to specific nuclear receptors, which

induce responsive genes. In vitamin A deficiency,

mucus-secreting cells are replaced by keratinproducing

cells.

• Retinoids are necessary for normal growth, fetal

development, fertility, haematopoiesis and immune

function.

Globally

, the most important consequence of

vitamin A deficiency is irreversible blindness in young

children.

Asia is most notably affected and the problem

is being addressed through widespread vitamin Asupplementation

programmes. Adults are not usually at

risk because liver stores can supply vitamin A when

foods containing vitamin A are unavailable

Early deficiency causes impaired adaptation to thedark (

night

blindness

). Keratinisation of the cornea

(

xerophthalmia

) gives rise to characteristic

Bitot’s spots

, and progresses to

keratomalacia

, with corneal ulceration,

scarring and irreversible blindness ).
Incountries where vitamin A deficiency is endemic, pregnant women should be advised to eat dark-green, leafy
vegetables and yellow fruits (to build up stores of retinol in the fetal liver), and infants should be fed the same.
WHO is according high priority to prevention in communities where xerophthalmia occurs, giving single
prophylactic oral doses of 60 mg retinyl palmitate (providing200 000 U retinol) to pre-school children.
Thisalso reduces mortality from gastroenteritis and respiratory
infections.

Repeated moderate or

high doses

of retinol can cause

liver damage

hyperostosis

and

teratogenicity

Women
in countries where deficiency is

not endemic

are therefore

advised not to take vitamin A supplements in pregnancy

Retinol intake may also be restricted in those at
risk of osteoporosis.

Acute overdose leads to nausea and

headache, increased intracranial pressure and skin
desquamation.

Excessive intake of carotene can cause pigmentation
of the skin (

hypercarotenosis

); this gradually

fades when intake is reduced.

The natural form of vitamin D

, cholecalciferol or

vitaminD

, is formed in the skin by the action of UV light on

7-dehydrocholesterol, a metabolite of cholesterol. Fewfoods contain vitamin D naturally and skin exposure to
sunlight is the main source. Moving away from theequator, the intensity of UV light decreases, so that at
a latitude above 50

° (including northern Europe),

vitamin D is not synthesised in winter, and even above
30

° there is seasonal variation.

The body store accumulated

during the summer is consumed during the winter.

Vitamin D is converted in the liver to 25-hydroxy vitamin

D (25(OH)D), which is further hydroxylated in thekidneys to 1,25-dihydroxy-vitamin D (1,25 (OH)

D), the

active form of the vitamin

1,25(OH)

D activates specific intracellular receptorswhich influence calcium metabolism, bone mineralisation

and tissue differentiation. The synthetic form

, ergocalciferol, or vitamin D

, is considered to be less potent

than the endogenous D

The effects of vitamin D deficiency (calcium
deficiency,
rickets and

osteomalacia

) are described on An

analogue of vitamin D (calcipotriol) is used for
treatment of skin conditions such as psoriasis.
Excessive
doses of cholecalciferol, ergocalciferol or the
hydroxylated

metabolites cause hypercalcaemia

Vitamihasn E

αtocopherol. many direct metabolic
actions:
• It prevents

oxidation of polyunsaturated

fatty acids

in cell membranes by free radicals.
1

helps maintain cell membrane structure

DNA synthesis

and cell signalling.

anti-inflammatory and immunesystems

Human deficiency is rare and has only been
described
in premature infants and in malabsorption. It can
cause a mild

haemolytic anaemia, ataxia

and

scotomas. visual

Vitamin K

is supplied in the diet mainly as

vitamin K

Gla(phylloquinone

) in the UK, or as vitamin

(menaquinone)

from fermented products in parts of Asia. Vitamin

is also synthesised by bacteria in the colon

. Vitamin

K is a co-factor

for carboxylation reactions

: in particular,

the production of

γ-carboxyglutamate (gla).

residues are found in four of the coagulation factor proteins
(II, VII, IX and X; , conferring their capacity
to bind to phospholipid surfaces in the presence of
calcium

. Other important gla proteins are osteocalcin

and matrix gla protein, which are important in bone
mineralisation

Vitamin K deficiency leads to

delayed coagulation

and bleeding.

In obstructive jaundice,

dietary vitamin K

is not absorbed and it is essential to administer the
vitamin in parenteral

form before surgery.

Warfarin and

related anticoagulants act by antagonising

vitamin K. Vitamin K is given routinely to newborn
babies to prevent haemorrhagic disease.

Symptoms of

excess have been reported only in infants, with synthetic
preparations linked to haemolysis and liver damage

Water-soluble vitamins

Thiamin (vitamin B1 )

Thiamin is widely distributed in foods of both vegetableand
animal origin. Thiamin pyrophosphate (TPP) isa co-factor for
enzyme reactions involved in themetabolism of macronutrients
(carbohydrate, fat andalcohol), including
• decarboxylation of pyruvate to acetyl-co-enzyme A,
which bridges between glycolysis and the
tricarboxylic acid (Krebs) cycle
• transketolase activity in the hexose monophosphate
shunt pathway
• decarboxylation of α-ketoglutarate to succinate in
the Krebs cycle.

In thiamin deficiency, cells cannot metabolise
glucoseaerobically to generate energy as
ATP. Neuronal cellsare most vulnerable,
since they depend almost exclusivelyon
glucose for energy requirements

Impaired

glucose oxidation

also causes an

accumulation ofpyruvic and lactic acids,
which produce vasodilatationand increased
cardiac output

Deficiency

– beri-beri

In the developed world, thiamin deficiency is
mainlyencountered in chronic

alcoholics. Poor diet,

impairedabsorption, storage

and phosphorylation of

thiamin inthe liver, and the increased requirements for
thiamin to metabolise ethanol all contribute. In the
developingworld, deficiency usually arises as a
consequence of adiet based on polished rice. The body
has very limitedstores of thiamin, so deficiency is manifest
after only

1month

on a thiamin-free diet. There are two

forms of thedisease in adults:

•

Dry (or neurological) beri-beri

manifests with chronic

peripheral neuropathy and with wrist and/or foot
drop, and may cause

Korsakoff’s psychosis

and

Wernicke’s encephalopathy

•

Wet (or cardiac) beri-beri

causes generalised oedema

due to biventricular heart failure with pulmonary
congestion.
In dry beri-beri, response to thiamin administration
is not uniformly good. However

multivitamin therapy

seems to produce some improvement, suggesting
that other vitamin deficiencies may be involved.

Wernicke’s encephalopathy and wet beri-beri should
be treated without delay with intravenous vitamin B
and C mixture (‘Pabrinex’,

Korsakoff’s psychosis

is irreversible and does not respond to thiamin

A rare but important effect of chronic alcohol misuse
is

the Wernicke

–Korsakoff syndrome

. This organic brain

disorder results from damage to the mamillary bodies,
dorsomedial nuclei of the thalamus and adjacent areas
of periventricular grey matter caused by a deficiency of
thiamin (vitamin B

), which most commonly results

from long-standing heavy drinking and an inadequate
diet. It can also arise from malabsorption or even protracted
vomiting. Without prompt treatment (see below),
the acute presentation of Wernicke’s encephalopathy

(nystagmus, ophthalmoplegia, ataxia and confusion

)

can progress to the irreversible deficits of

Korsakoff’s

syndrome (severe short-term memory deficits and
confabulation, and also reduced red blood cell transketolase).
In those who die in the acute stage, microscopic
examination of the brain shows hyperaemia,
petechial haemorrhages and astrocytic prolifera

Riboflavin (vitamin B

)

Riboflavin is required for the

flavin co-factors

involved
in oxidation

–reduction reactions. It is widely

distributed
in

animal and vegetable foods

. Levels are low in staple

cereals but germination increases its content. It is

destroyed under alkaline conditions

by heat and by

exposure to sunlight.
Deficiency is rare in developed countries. It mainly
affects the tongue and lips and manifests as

glossitis,

angular stomatitis

and

cheilosis.

The genitals may be

affected, as well as the skin areas rich in sebaceous
glands, causing

nasolabial or facial dyssebacea

Rapid

Niacin (vitamin B

)

Niacin encompasses

nicotinic acid and nicotinamide

. Nicotinamide is an essential part of the two

pyridinenucleotides,

nicotinamide adenine dinucleotide (NAD

) and

nicotinamide adenine dinucleotide phosphate

(NADP),

which play a key role as hydrogen acceptors and donors for many enzymes. Niacin can be synthesised

in the body in limited amounts from the aminoacid tryptophan
.

Deficiency

– pellagra

Pellagra was formerly endemic among poor people whosubsisted chiefly on maize, which contains niacytin, a

form of niacin that the body is unable to utilise. Pellagracan develop in

only 8 weeks

in individuals eating

diets
that are very deficient in niacin and tryptophanremains a problem in parts of Africa

, and is occasionally

seen in

alcoholics

and in patients with

chronic smallintestinal disease

in developed countries.

Pellagra canoccur in

Hartnup’s disease

, a genetic disorder characterisedby impaired absorption of several

amino acids, including tryptophan.
It is also seen occasionally in

carcinoid syndrome

, when tryptophan is consumed

in the excessive production of

5-hydroxytryptamine(5-HT).

Pellagra has been called the disease of the

three D

•

Dermatitis

Characteristically, there is erythema resembling severe

sunburn, appearing symmetrically over the parts of the body exposed to
sunlight, particularly the limbs and especially on the neck, but not the
face (

Casal’s necklace,

The skin lesions may progress tovesiculation, cracking, exudation and
secondaryinfection.

•

Diarrhoea

. This is often associated with anorexia, nausea, glossitis

and dysphagia, reflecting thepresence of a non-infective inflammation
thatextends throughout the gastrointestinal tract.

•

Dementia

. In severe deficiency, delirium occursacutely and dementia

develops in chronic cases

Toxicity

Excessive intakes of niacin may lead to
reversible

hepatotoxicity

Nicotinic acid is a lipid-lowering agent,
but at doses above 200 mg a day gives
rise to vasodilatory symptoms (‘

flushing

’

and/or

hypotension

)

Pyridoxine (vitamin B

)

Pyridoxine, pyridoxal and pyridoxamine are differentforms of vitamin B

that undergo phosphorylation to

produce pyridoxal 5-phosphate (PLP). PLP is theco-factor for a large number of enzymes involved in the
metabolism of amino acids. Vitamin B

is available inmost foods.

Deficiency is rare, although certain drugs, such

asisoniazid and penicillamine

, act as chemical antagonists

to pyridoxine.
Pyridoxine administration is effectivein isoniazid-induced

peripheral neuropathy

and some

cases of

sideroblastic anaemia

Large doses of vitaminB

have

an antiemetic effect in radiotherapy-induced

nausea

Although vitamin B

supplements have become popular in the treatment of nausea in pregnancy, carpal

tunnel syndrome and premenstrual syndrome, there is no convincing evidence of benefit.

Very high doses

ofvitamin B

taken for several months can cause a

sensorypolyneuropathy

Biotin

Biotin is a co-enzyme in the synthesis of

fatty

acids,

isoleucine and valine and is also involved in

gluconeogenesis

Deficiency results from consuming very large
quantities of raw egg whites

(> 30%

energy

intake)
because

the

avidin

they contain binds to and

inactivatesbiotin in the intestine. It may also be
seen after long periods of total parenteral
nutrition. The clinical features of deficiency include
scaly dermatitis, alopecia and paraesthesia

.

Folate (folic acid)

Folates exist in many forms. The main circulating formis

methyltetrahydrofolate.

Folic acid is the stable synthetic form. Folate works

as a methyl donor for cellular methylationand protein synthesis. It is
directly involved in DNAand RNA synthesis, and requirements increase
during embryonic development

Folate deficiency may cause three major birth defects

(

spina bifida, anencephaly and encephalocele

) resulting

from imperfect closure of the neural tube, which

takesplace 3

–4

weeks

after conception.

Departmentof Health advises that women who have experienced a
pregnancy affected by a neural tube defect should

take5 mg

of folic acid daily

from before conception andthroughout the first trimester
All

women planning a pregnancy are advised to include good sources of
folate in their diet, and to take folate supplements throughout the first
trimester. Liver is the richest source of folate but an alternative source
(e.g.

leafy vegetables

) is advised in early pregnancy because of the

high vitamin A content of liver

Folate deficiency also has been associated with

heart disease

dementia

and

cancer.

. There are now concerns that this may contribute to the increased

incidence of

colon cancer

through promotion of the growth of polyps.

Hydroxycobalamin (vitamin B

)

Vitamin B

is a co-factor in folate co-enzyme recyclingand nerve myelination. Vitamin B

and

folate are particularlyimportant in DNA synthesis in red blood cells

The haematological disorders (macrocytic ormegaloblastic anaemias) due to their deficiency
are discussedon . Vitamin B

, but not folate, is needed for the integrity of myelin, so that

vitamin B

deficiency is also associated with neurological disease

Neurological consequences of vitamin B

deficiency

In older people and

chronic alcoholics

, vitamin B

deficiencyarises from

insufficient intake and/or frommalabsorption. Several drugs, including

neomycin, canrender vitamin B

inactive

Adequate intake of folatemaintains

erythropoiesis

and there is a concern

that fortification of foods with folate may mask underlyingvitamin B

deficiency. In severe deficiency there is insidious, diffuse and uneven

demyelination

. It may be clinically manifest

as peripheral neuropathy

spinalcord degeneration

affecting

both posterior and lateral columns

(‘

subacute combined degeneration of the spinal

cord’ or there may be cerebral
manifestations(resembling dementia) or optic
atrophy

Vitamin B

therapy improves symptoms in most cases

The average daily diet contains 5

–30 μg of vitamin B

mainly in

meat, fish, eggs and milk

– well in excess of

the 1

μg daily requirement. In the stomach, gastric

enzymes release vitamin B

from food and at

gastric pH

binds to a carrier protein termed R protein

. The gastric

parietal cells produce

intrinsic factor

, a vitamin B

binding protein which optimally binds vitamin B

at pH

8. As gastric emptying occurs, pancreatic secretion raises
the pH and vitamin B

released from the diet switches

from the R protein to intrinsic factor.

Bile also contains

vitamin B

which is available for reabsorption in the

intestine

. The vitamin B

–intrinsic factor complex binds

to specific receptors in the terminal ileum, and vitamin
B

is actively transported by the enterocytes to plasma

where it binds to transcobalamin II, a transport protein
produced by the liver, which carries it to the tissues for
utilisation.

The liver stores enough vitamin B12 for
3 years and this, together with the enterohepatic
circulation,

.
Blood levels of vitamin B12 provide a reasonable
indicationof tissue stores and are usually diagnostic of
deficiency. Levels of cobalamins

fall in normal pregnancy.

Reference ranges vary between laboratories but levels
below 150 ng/L are common and, in

the last trimester

Spuriously

low B12 values occur in women using the oral
contraceptive pill

and in patients with myeloma,.