9/18/2017

FAT SOLUBLE
VITAMINS

Made Astawan
Dept. of Food Science & Technology
Bogor Agricultural University

Vitamin Absorption

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The role of vitamins in metabolism of

macronutrient

Introduction

 Vitamins and minerals are classified as

micronutrients: chemical substances required for
normal growth and metabolism.

 Although micronutrients are found in all body tissues

and fluids, they account for only a small percentage of
body weight.

 Higher living organisms rely on ingesting food and

supplements to meet their vitamin and mineral needs.

 Known exceptions to this rule are the production of

vitamin K and biotin by gut microorganisms and the
synthesis of vitamin D from its precursor form under
the skin.

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Functions of Vitamins

 Organic compounds

 Involved in the release of energy from carbohydrates,

fats, and proteins by functioning as co-enzymes.

 They do not yield energy themselves

 Function both dependently and independently

 One vitamin can not substitute for another.

What is a vitamin?
Vitamin:
- A vitamin is any organic compounds required by the
body in small amounts for metabolism, to protect health,
and for proper growth in children.
- They also assist in the formation of hormones, blood
cells, nervous-system chemicals,and genetic materials.

Vitamins taken in to the body in excess of the bodies

needs are useless
Excess water soluble vitamins are excreted mainly in
the urine
Fat soluble vitamins are stored in the body and could
become toxic in very large excess

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Types of Vitamins
 Fat Soluble Vitamins:  Water Soluble Vitamins:

- Vitamins A, D, E, and K. - Vitamins B-8 and C.

- Are consumed with fat - - Cannot be stored.
containing foods, and can - Must be
be stored in the body’s fat consumed
- Does not have to be frequently.
consumed daily.
 Vitamin D:
- Vitamin D is the only vitamin that the body can
manufacture.
All of vitamins must be derived from the diet.
A well-balance diet contains all of the necessary vitamins
needed for the body.

The vitamins
A Retinol, -carotene
D Calciferol
E Tocopherols, tocotrienols
K Phylloquinone, menaquinones, menadione
B1 Thiamin
B2 Riboflavin
B3 Niacin, nicotinic acid, nicotinamide
B5 Pantothenic acid
B6 Pyridoxine, pyridoxal, pyridoxamine
B12 Cobalamin
Folate Folic acid
H Biotin
C Ascorbic acid


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Compounds that are not dietary

essentials but may have protective
actions
Bioflavonoids
Ubiquinone (coenzyme Q)
Polyphenols
Anthocyanins
Vitamin A inactive carotenes
Glucosinolates, glycosides
Squalene, polyterpenes
Phyto-oestrogens
Antioxidant actions
Antioxidant actions
Antioxidant actions
Antioxidant actions
Antioxidant actions
Modify metabolism of foreign
compounds / procarcinogens
Inhibit cholesterol synthesis
Anti-oestrogenic actions


Marginal compounds, (probably)

not dietary essentials
Bioflavonoids (“vitamin P”)
Carnitine

Choline

Inositol

Pyrroloquinolone quinone (PQQ)

Taurine

Ubiquinone (coenzyme Q, “vitamin Q”)

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Vitamin Requirements: RDA

 RDA established to meet the needs of healthy people under
usual environmental stress.
 Developed by the subcommittee of the Food and Nutrition
Board of the National Academy of Sciences
 Often exceed actual individual nutritional requirements
because they are two standard deviations above the mean
requirements.
 Meeting 2/3 of the RDA is considered adequate, but
requirements change throughout life.

Dietary Reference Intakes (DRI)

 Established in 1997 by National Academy of
Sciences to update RDA guidelines.
 Focus more on prevention of disease.

Vitamin Deficiencies
 In the US, vitamin and mineral deficiencies have
significantly dropped since 1900 but still exist.
 When deficiencies occur due to overall poor intake, more
than one vitamin and/or mineral is responsible.

 Vitamins and minerals function together in metabolism

and therefore, one deficiency may exacerbate another.

Classic Deficiency States

Disease Vitamin Deficiency
Scurvy Vitamin C
Beriberi Thiamin
Pellagra Niacin
Goiter and cretinism Iodine
Rickets Vitamin D
Pernicious Anemia Vitamin B12

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Vitamin Toxicity
 “More is not always better.”
 More commonly reported with fat-soluble vitamins.
 Large doses of vitamin C has been reported to
predispose individual to oxalate stones.
 Large doses of vitamin C can produce false-negative
urine glucose test results in patients with diabetes.
 Taking folic acid may mask a vitamin B12 deficiency.
 Vitamin A toxicity may have teratogenic effects on
the fetus.

Who Needs Vitamin and

Mineral Supplements?

 Patients with the following:

– Inadequate food intake (elderly, dieters, restricted diets)
– Increased nutrient requirements (pregnancy/lactation)
– Increased metabolic demands (surgery/trauma/fracture)
– Maldigestion or malabsorption (liver disease, GI,
diarrhea)
– Drug-nutrient interactions (weight changes, electrolytes)
– Medical treatment interactions (chemo/radiation)
– Need for pharmacological doses (niacin for CVD)
– Primary prevention of disease (folate, vitamin E)

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Fat Soluble Vitamins

Vitamin Main functions
A Essential for vision in dim
light; necessary for
maintenance of mucous
membranes, skin and
growth.
D Promotes calcium and
phosphate absorption
from food and is thus
essential for bones and
teeth.
E Protects cell membranes
from damage by oxida
tion.
Sources
As retinol in milk,
fortified margarine,
butter, cheese, egg
yolk, liver and fatty fish.
As carotenes in milk,
carrots, tomatoes, dark
green vegeta bles.
Sunshine, fortified
margarine, oily fish,
egg yolk, fortified
breakfast cereals.
Vegetable oils, nuts,
vegeta bles and
cereals.
Deficiency Excess
Reduced night vision; loss Vitamin A is
of sight through gradual stored in the liver
damage to the cornea. and toxicity can
Lowered resistance to occur.
infection.
Failure of bones to grow Vitamin D can be
and calcify leading to toxic.
rickets in children and
osteomalacia in adults.
Deficiency may occur in Not known.
premature infants or due
to malabsorption.

K Essential in the formation Synthesis by bacteria Deficiency leads to an Not known.

of blood clottingproteins. in the gut. Dark green increased clotting time.
leafy vegeta bles, eg
cabbage, brussel
sprouts and spinach.

Vitamin A

 Nomenclature: Vitamin A refers to compounds or

mixtures of compounds having vitamin A activity.

– In animals, preformed vitamin A usually exist as

retinol, retinyl esters, retinal, and retinoic acid.

– In plants, vitamin A exists in its precursor form,

provitamin A, carotinoids and cryptoxanthin.

– Transretinol is the active component.

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Functions of Vitamin A
 Normal vision- formation of rhodopsin (retinal
pigment) from retinal and opsin.
 Normal integrity and growth of epithelial cells,
which moisten the linings of the eye, the
respiratory and GI tracts.
 Collagen production- teeth, bones, cartilage,
tendons, and connective tissue.
“cilia”
 Normal reproduction.
 Promotion of cellular
differentiation. sel epithel normal (bulat, lembab)

 Normal membrane integrity

sel epithel “keratinized”
and function. (irregular, kering)

Vision Process

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Vitamin A Utilization
 Ingest carotenoids mostly from vegetables (dark-green
leafy and deep-yellow vegetables).
 Converted to retinol then retinal in gut for transport .
 Absorption occurs in the ileum and requires bile salts.
Transported to the liver for storage in the form of retinyl
ester.
 Transported to tissues via retinal binding protein.
 RDA expressed in RE/day; 1000 ug RE / d for males and
800 ug RE / d for females.

Vitamin A deficiency
 impairment of senses of balance and taste
 impaired colour vision
 impaired dark adaptation
 inability to see in dim light (night blindness)
 failure of growth
 impaired immune responses
 keratinization of skin
 squamous metaplasia and keratinization of
conjunctiva
 dryness wrinkling and thickening of cornea
(xerophthalmia)
 keratinization of cornea
 ulceration of cornea (blindness)


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Vitamin A toxicity
 central nervous system
 increased intracerebral pressure
 headache, nausea, ataxia, anorexia
 liver
 histological changes
 fibrosis, hepatomegaly, hyperlipidemia
 hypercalcemia
 joint pains, thickening of long bones
 hypertensive encephalopathy
 skin
 excessive dryness, scaling and chapping
 desquamation and alopecia


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Vitamin A and retinoids

vitamin A
 any compound with vitamin activity
 ie will prevent or cure deficiency
 includes preformed vitamin A
(retinol and its active metabolites)
 and pro-vitamin A carotenes

retinoids
 retinol and its derivatives and analogues
 naturally occurring or synthetic
 with or without vitamin activity


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Biologically active retinoids

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH2OH
CH3 CH3
retinol
11-cis-retinol
CH3 CH2OH

CH3 CH3 CH3 CH3

CHO

retinaldehyde
CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3
COOH
CH3
all-trans-retinoic acid 9-cis-retinoic acid
CH3
H3C
COOH 

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Formation of retinol and

retinoic acid

CH3 CH3
H3C CH3
CHO

retinaldehyde
CH3
NAD(P)H
aldehyde oxidase
retinol dehydrogenase
NAD(P)+

CH3 CH3 CH3 CH3

H3C CH3 H3C CH3
CH2OH COOH

retinol retinoic acid

CH3 CH3

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Theoretically 1 mol of carotene  2

mol retinaldehyde
H3 C
CH3 CH3
H3C CH3

H3C CH3
CH3 CH3
CH3 -carotene
O2
carotene dioxygenase
H3C
CH3 CH3
H3C CH3

H3C CH3
O O CH3 CH3
CH3

CH3 CH3
H3C CH3
CHO

retinaldehyde
CH3
Experimentally 6 mg -carotene is equivalent to <1 mg retinol 

VITAMIN D

Calciferol
Function to increase the efficiency of
intestinal calcium absorption and to
mobilize calcium stores from bone in
order to maintain the serum calcium and
phosphorus concentrations within the
normal physiological range.

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Vitamin D
Formation Vitamin D3 (cholecalciferol) and vitamin D2
(ergocalciferol) are stored in body fat.
The vitamin D precursors produced in yeast and plants
(ergosterol) and animals (7-dehydrocholesterol) are
converted to vitamin D by exposure to ultraviolet light.

Vitamin D (either vitamin D2 or vitamin D3) is

metabolized in the liver to 25-hydroxyvitamin D and then
to 1, 25-dihydroxyvitamin D in the kidney.

1, 25-Dihydroxyvitamin D is considered to be the

biologically functioning form of vitamin D.

Vitamin D
 Ingested as ergocalciferol (D2) or cholecalciferol (D3)
 Synthesized from 7-dehydrocholesterol in the skin
after sun exposure.
 Activated by undergoing 25-hydroxylation in the liver
followed by 1-hydroxylation in the kidneys to become
1,25 (OH)2-D3.
 Active form acts on bones, kidneys and intestine to:
– Increase calcium absorption
– Increase bone calcification and reabsorption
– Maintain calcium, phosphate and bone homeostasis

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Vitamin D
Food sources:
1. Non dietary by conversion inside the body
2. Dietary Good food sources are milk properly fortified
with vitamin D, fatty fish such as salmon and mackerel
cod liver oil, fish liver oil, some breads and cereals,
and some egg yolks.
Not affected by storage or preservation or cooking
Diet recommendations.
Based on the available literature and assuming some
exposure to sunlight, an AI for ages 0 - 50 years was set
at 200 IU (5 g)/day. There was no compelling data to
increase the vitamin D requirement either during
pregnancy or lactation..

Vitamin D

Deficiencies: In humans
- rickets in children
- osteomalacia in adults
- muscle weakness
- bony deformities
- neuromuscular irritability causing muscle
spasms of the larynx (laryngospasm) and
hands (carpopedal spasm)
- generalized convulsions and tetany.

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Vitamin D
deficiency causes rickets in children, osteomalacia in adults

Rickets
undermineralization of bone
Osteomalacia
demineralization of bone

The main rôle of vitamin D is in calcium homeostasis

it acts as a nuclear hormone, regulating gene expression.
It can by synthesized in the skin if there is adequate sunlight.

Actions of vitamin D
Maintenance of plasma calcium
 increased intestinal absorption of calcium.
 reduced excretion of calcium
 by stimulating resorption in the distal renal tubules.
 mobilization of bone mineral

Permissive or modulatory effects

a necessary, but not sufficient, factor, in:
 insulin secretion
 synthesis and secretion of parathyroid and thyroid
hormones
 inhibition of production of interleukin and
immunoglobulin by activated lymphocytes
 differentiation of monocyte precursor cells.
 modulation of cell proliferation


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Vitamin D
Calcium
Homeostasis
1,25 dihydroxyvitamin D

Bone Re absorption
(osteoclasts)
Bone Calcium Intestine
Absorption
Bone Formation

Blood Calcium
2.1-2.6 mM

skin

7-dehydrocholesterol Previtamin D3 Inactive compounds

D3 (Cholecalciferol)

blood DBP (vit. D binding protein)

DBP-D3
Ca++ transport Ca++ resorption
(intestine) (bone)
D3
liver
kidney 1, 25-OH D3 (active)
25-OH D3
(calcidiol) (calcitriol)
25-OH D3
DBP-calcidiol
24, 25-OH D3 (inactive)
(tight binding)

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Vitamin E

 Vitamin E occurs naturally in compounds known as

tocopherols and tocotrienols.
 Alpha-tocopherol is the most active form.
 Absorbed with fats via the lymphatic system.
 Transported in lipoproteins.
 Vitamin E functions as a chain breaking antioxidant,
preventing further auto-oxidation of lipids.
 Richest sources of vitamin E are vegetable oils.
 Clinical deficiency of vitamin E most commonly due
to severe malabsorption.

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Vitamin E deficiency
 female animals – death and resorption of the fetuses
 male animals – testicular atrophy and degeneration of
the germinal epithelium of the seminiferous tubules
 necrotizing myopathy
 exudative diathesis
 leakage of blood plasma into subcutaneous tissues
 accumulation under the skin of a green-coloured
fluid
 central nervous system necrosis and axonal dystrophy
 exacerbated by feeding diets rich in PUFA

Functions of Vitamin E
Chain-breaking antioxidant
Protects cell membranes
Enhances immune response
Regulates platelet aggregation
Regulates protein kinase C activation

PUFA :H PUFA *

PUFA * + O2 PUFA :OO *

PUFA :OO* + PUFA :H PUFA :OOH + PUFA *

Vitamin E Breaks the chain by donating hydrogen Forming a

stable species

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Vitamin E as an antioxidant

R1 R+ TOH  RH + TO 

HO
CH 3
Phythyl Tail .O CH 3 CH 3
R2 O
R3 (CH 2)3CH(CH 2)3CH(CH 2)3CH(CH 3)2
CH 3 O CH 3
Chromane Head
CH 3

R1 R2 R3
CH 3 CH 3 CH 3

CH 3 H CH 3

 H CH 3 CH 3
 H H CH3

Vitamin E as an antioxidant
CH3

HO
CH2OH

HO CH
H3C O O
CH3
O
CH3 tocopherol

O OH
lipid peroxide
monodehydroascorbate
(semidehydroascorbate)
fatty acid CH2OH

CH3
HO CH
O
O
O

OH OH
H3C O
CH3 ascorbate
CH3
tocopheroxyl radical


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Vitamin E
Sources, Intakes & Requirements
Vegetable oils, sunflower seeds and nuts are
the richest dietary sources
RDA is 15 mg alpha-tocopherol (22.5 IU)
Optimal vitamin E intakes may be 100 - 400
IU per day
Natural-source is a single isomer
(d-alpha-tocopherol)
Synthetic is a mixture of eight isomers
Natural-source has twice the bioavailability of
synthetic

Vitamin E vitamers
CH3 CH3
HO HO
-tocopherol -tocotrienol

H3C O H3C O
CH3 CH3
CH3 CH3

CH3 CH3
HO -tocopherol HO -tocotrienol

O O
CH3 CH3
CH3 CH3

HO HO -tocotrienol
-tocopherol

H3C O H3C O CH3

CH3
CH3 CH3

HO HO
-tocopherol -tocotrienol

O O CH3
CH3
CH3 CH3

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Vitamin E

Absorption and Transport

Dependent on ability to absorb fat
Absorbed into lymphatic system
Component of chylomicrons
Alpha-tocopherol is major tocopherol in
plasma
Positive association between serum lipid and
tocopherol levels
Normal range is 0.5-1.6 mg/dl

Vitamin E

Protective Role in Disease Prevention

There is extensive evidence implicating

oxidative damage in the development of
degenerative diseases and conditions.
A number of studies have evaluated the role
of vitamin E, alone or in combination with
other antioxidants, in preventing or minimizing
oxidative damage associated with
development of cancer, coronary heart
disease, cataracts and Alzheimer’s disease.

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Vitamin E & Cancer

Majority of epidemiologic studies showed an inverse
association between vitamin E status and subsequent
risk of certain cancers

Intervention trials have shown mixed results

– Reduced cancer incidence and decreased mortality
rate from stomach and esophageal cancers in China
– No decrease in recurring colorectal tumors in U.S.
– Improvement in precancerous oral lesions in U.S.
– Decreased incidence and mortality of prostate cancer
but not lung cancer in Finland

Vitamin E, CHD & Cataracts

Increased vitamin E intakes associated with
decreased risk of coronary heart disease in
epidemiologic studies
Vitamin E showed protective effects

Vitamin E delayed or minimized cataract

development in animal models
Epidemiologic data suggest a relationship
between blood vitamin E levels and cataract
risk
Decreased cataract risk associated with
vitamin E supplementation

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Vitamin E & Alzheimer’s Disease

Increased vitamin E intakes or blood levels
associated with reduced risk of Alzheimer’s
disease
Vitamin E or selegiline slowed disease
progression in multicenter trial
Current practice guidelines recommend
vitamin E or selegiline for patients with
moderate disease
Vitamin E may be preferred from a safety
standpoint

Vitamin E Safety

Few side effects in double-blind, controlled

human studies
Could affect blood clotting in patients on blood
thinners
No other specific side effects
UL set at 1,000 mg per day for adults
Vitamin E is safe and well tolerated over wide
range of intakes and time periods

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Vitamin K

Function Essential for blood clotting

and its regulation
Sources cooked dark green
vegetables, such as spinach, kale and
broccoli
Deficiency disruption of blood
clotting
Absorption along with fat that
assisted by emulsifying action of bile

Vitamin K
 Functions as a co-factor for the synthesis of
prothrombin and several other proteins involved
in clotting cascade.
 Synthesized by bacteria in small intestine.
 Sources include dark green leafy vegetables.
 Malabsorption syndrome, biliary obstruction, and
oral use of sulfa or antibiotics may lead to
deficiency.
 Deficiency results in prolonged clotting time and
hemorrhage in newborns (check PT levels).
 Interferes with coumadin therapy.
 RDA: 80 ug/d for adult males; 65 ug/d for females.

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Vitamin K
O
CH3

OH OH

O 3 CH2
phylloquinone

O O O O
O
dicoumarol
CH3
CH3
CO
n CH2
O CH3 OH
menaquinone CH
CO
OH O
CH3 CH3 O O
Warfarin

menadioldiacetate
OH O (acetomenaphthone)
menadiol
C O
CH3

Recommended Dietary Intake of fat soluble vitamins (WNPG, 2004)

Age group (y) Vit A (µg) Vit D (µg) Vit E (mg) Vit K (µg)

<1 380 5 5 8
1–3 400 5 6 15
4–6 450 5 7 20
7-9 500 5 7 25
Male : 10 – 12 600 5 11 35
13 – 15 600 5 15 55
16 – 18 600 5 15 55
19 – 29 600 5 15 65
30 – 49 600 5 15 65
50 – 64 600 10 15 65
65+ 600 15 15 65
Female: 10 - 12 600 5 11 35
13 – 15 600 5 15 55
16 – 18 600 5 15 55
19 – 29 500 5 15 55
30 – 49 500 5 15 55
50 – 64 500 10 15 55
65+ 500 15 15 55

Pregnant 800 5 15 55
Lactation 850 5 19 55

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