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© Endeavour College of Natural Health endeavour.edu.au 1 NMDF121 Session 15 FAT SOLUBLE VITAMINS PART 1 Naturopathic Medicine Department

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Page 1: NMDF121 SN15 Lecture FSV1 · 2017-02-15 · • Rough, dry and scaly skin • Perifollicular hyperkeratosis on the lateral aspects of the upper arms and the thighs (Heimburger 2006)

© Endeavour College of Natural Health endeavour.edu.au 1

NMDF121

Session 15

FAT SOLUBLE VITAMINS

PART 1

Naturopathic Medicine

Department

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Topic Summary

• Fat Soluble Vitamins

• Introduction to Fat Soluble Vitamins

• Vitamin D

• Vitamin A

• Structure and requirements

• Functions and metabolism

• Therapeutic uses

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Fat Soluble Vitamins

• Include vitamins A, D, E and K

• Differ from water-soluble vitamins in several significant

ways:

Whitney & Rolfes, 2008

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Fat Soluble Vitamins

• Participate in numerous activities throughout the body:

• Vitamin A – Primarily involved in eye function, skin health,

nervous system, bone tissue and immune function

• Vitamin D – Regulates bone mineral metabolism and cell

differentiation

• Vitamin E – Antioxidant

• Vitamin K – Involved in blood

clotting and bone mineralisation

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Fat Soluble Vitamins

• Digestion and absorption are similar to other lipids

• Requires bile salts

• Involves chylomicrons

• Stored in body lipids

• Excesses are stored primarily in liver and adipose tissue.

• Body maintains blood concentrations by drawing on stores.

• Risk of toxicity is greater than for the water-soluble vitamins.

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Fat Soluble Vitamins

• Important….

• Fat soluble vitamins do not work independently similar to

many B vitamins which coordinate and regulate the

body’s energy metabolism pathways.

• A, E, D and carotenoids orchestrate gene transcription

• Vitamin E and carotenoids act as antioxidants

• A, D and K contribute to bone health

• A, E, D, K for blood health

• A, carotenoids and E essential eye health

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Vitamin D - Cholecalciferol

http://commons.wikimedia.or

g/wiki/File:Cholecalciferol.pn

g

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Vitamin D - Cholecalciferol

Food Amount Vitamin D (IU)

Medicinal Cod Liver Oil 1 tbsp 2271

Pink salmon, canned 100g 624

Oysters 6 oysters 269

Whole milk, fortified 1 cup 92.7

Beef salami 1 slice 80.3

Shrimp 4 large 42.6

Egg yolk 1 large 24.6

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Vitamin D - Cholecalciferol

• Also known as calciferol, 1,25-dihydroxy vitamin D (calcitriol), vitamin D3 or cholecalciferol (animal sources only), vitamin D2 or ergocalciferol (vegetable/plant sources)

• Non-essential nutrient, as body can make vitamin D from sunlight and cholesterol

• Acts like a hormone in the body

• Once the vitamin is synthesised, it must become activated via the liver and kidneys.

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Vitamin D Production

• In vivo production

• Synthesised in the

sebaceous glands from

cholesterol

• Exposure to sunlight

converts it to previtamin D3

• 2-3 days to convert it to

cholecalciferol (vitamin D3)

Rolfes, Pinna and Whitney,

2009

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Functions

• Calcitriol (active form) functions like a steroid

hormone.

• Calcium homeostasis

Small intestine – upregulates genes which code

proteins to transport calcium into the enterocytes

Kidney – with PTH reduces urinary excretion

Bone – with PTH stimulate bone breakdown by

osteoclasts to regulate serum calcium levels.

o When serum Ca low PTH is stimulated to increase

conversion of inactive Vitamin D to active Vitamin D to

enable the above effects (Norman, 2006)

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Functions

• Cell differentiation

• Affects growth and maturation of

a wide range of cell types

• Enters the nucleus and up-

regulates selected genes coding

specific proteins eg. Bone

marrow and enterocytes

• Similar to vitamin A in epithelial

cells

• Possible cancer risk reduction

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Functions

• Many other tissues also respond to vitamin D • Immune system

• Brain

• Nervous system

• Pancreas

• Skin

• Muscles

• Cartilage

• Reproductive organs

(Norman 2006)

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Factors Increasing Demand

• Elderly, sick, debilitated, disabled with lack of sunshine

• Northern latitudes in the winter season

• Dark skin especially in outer latitudes

• Fat malabsorption

• Chronic kidney failure

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Activityo Review the recommendations from the RACGP

regarding the testing of Vitamin D status

http://www.racgp.org.au/afp/2014/march/vitamin-d/

o Also review the guidelines from the Cancer Council of

Australia

http://www.cancer.org.au/preventing-cancer/sun-

protection/vitamin-d/

o Discuss these recommendations in small groups or

on The Loop for online students – are the guidelines

clear enough?

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Deficiency Symptoms

• Rickets - children

• Failure of bone to mineralise

• No matrix replacing epiphyseal cartilage

• Bowed legs and knocked knees

• Curvature of the spine and thoracic deformities

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Rickets

Rolfes, Pinna and Whitney, 2009

Bowed Legs Beaded Ribs

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Deficiency Symptoms

• Osteomalacia - adults

• Impaired absorption of calcium and phosphorous.

• Bone matrix remains but lack of minerals makes bones soft and painful.

• Pain in pelvis, lower back, and legs

• Progressive weakness

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Deficiency Symptoms

• Proximal muscle weakness (Haddad 1974)

• Stunted growth (Cashman 2008)

• Seizures (Schnadower 2006)

• Bowing of the arms, knock-knees or outward bowing (Welsh 2000)

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Toxicity

• Toxicity more likely than other vitamins.

• Vitamin D from sunlight and food is not likely to cause

toxicity.

• High-dose supplements may cause toxicity.

• >100,000IU Hypervitaminosis D

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Toxicity Symptoms

• Hypercalcaemia → Calcification

of soft tissue such as kidney,

heart, lungs, blood vessels.

• Renal dysfunction, frequent

urination

• Polyuria, polydypsia

• Anorexia

• Nausea

• Weakness

• Hypertension

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Activity

• Watch the following video on ‘The truth about vitamin

D’ (5 mins)

http://www.youtube.com/watch?v=a2BrkPMRcZ8

• Consider this video and the previous activity looking at

Australian recommendations

• Discuss your views initially in small groups then with

the class group

• Online students should discuss this in the relevant

discussion forum

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Therapeutic Uses

• Autoimmune disease reduces inflammatory

cytokine expression

• May assist in Multiple sclerosis (Mark and Carson, 2006)

• Associated with prevention of type I diabetes (Mathieu and

Badenhoop, 2005)

• Elderly

• Reduce bone loss

• Improve muscle performance

• Optimum bone mass associated with reduced risk of falls

and fractures (Dawson-Hughes 2007)

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Therapeutic Uses

• Osteoporosis (Drinka, 2006)

• Cancer

• Evidence from experimental studies indicate that

vitamin D inhibits tumor cell proliferation, particularly

of breast cancer cell lines. The results from human

clinical trials on the effects of vitamin D

supplementation is emerging (Murillo and Mehta, 2005)

• Cystic Fibrosis

• Reduce the rate of bone turnover and bone loss in

adult patients with cystic fibrosis (Haworth et al, 2004)

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RDI

• Therapeutic range (adult) 400 to1600 IU

• UL 80mcg/day • Note: 40 IU equivalent to 1

mcg

NHMRC 2009

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Review Questions

1. List the foods highest in Vitamin D

2. How is vitamin D synthesised endogenously?

3. Generally speaking when are the best times during

the year and during the day to obtain adequate

UVB rays?

4. What are the main functions of Vitamin D?

5. Which factors may increase the demand for

Vitamin D intake?

6. How might we recognise a Vitamin D deficiency?

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Activity

• Consider your vitamin D intake from the previous 2

diet diaries you have entered into your diet analysis

programme and answer the following questions –

1. Are there any notable differences between the 24 hour and 3

day average intake?

2. Would you recommend increased intakes from the RDI?

3. If so what is your rationale behind this? Think specific and

patient related and also from a more general context

4. Are there any specific dietary recommendations you would

make to optimise your intake? Include specific food choices

and quantities to reach your target.

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Vitamin A and Beta-carotene

http://commons.wikimedia.org/w

iki/File:Vitamin_A.gif

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Vitamin A

• Vitamin A is found in the body in compounds known as retinoids: retinol, retinal, and retinoic acid.

• All preformed vitamin A – retinol (most active)

• Retinal can convert to retinol and retinoic acid

Pinna, Rolfes &

Whitney, 2009

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Vitamin A

• Vitamin A family also contains carotenoids

• Provitamin A – beta carotene (can convert to vitamin A)

• Non provitamin A – lycopene, lutein, zeaxanthin (phytonutrients)

• Measured in Retinol Activity Equivalents

– 1 RAE = 1 mcg retinol = 6 mcg beta carotene = 12 mcg of

other carotenoids

• Sources Vitamin A:

• Animal foods, whole fat dairy and fortified food as preformed Vit A

• Plant foods as provitamin A

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Vitamin A

Food Amount Vitamin A (mcg)

Liver, fried 100g 10,729

Cod Liver oil 1 tbsp 4,080

Carrot, raw ½ cup 1,715

Squash 1 cup 1,435

Mangoes 1 fruit 805

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Vitamin A

• Somewhat unstable and easily

lost during cooking and storing

• Prolonged freezing, heating

and light or oxygen exposure

can destroy much or both

preformed and pro vitamin A

carotenoids

• Beta-carotene may be

exception as processing and

heating seems to increase

bioavailability

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Functions

• Visual cycle

Rolfes, Pinna & Whitney, 2009

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Functions

• Cellular differentiation and maturation– Cell signaling and stimulating synthesis of proteins via up-

regulating gene expression (similar to vitamin D in other cells)

• Growth• Increases growth factor receptors

• Bone development and maintenance– Involved with osteoblasts and osteoclasts

– Too high levels interfere with calcium absorption

• Increases iron utilisation for hemoglobin formation

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Functions

o Regulation of gene expression (Higdon, 2003)

o Red blood cell production (Higdon, 2003)

o Growth and development (Higdon, 2003)

• Immune system function• Maintenance of protective linings

of GI and respiratory tracts

• Produces functional immune cells

such as lymphocytes and antibodies

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Factors Increasing Demand

• Growth periods, newborns

• Stress, infection surgery

• Fat malabsorption

• Diabetes and hypothyroidism

• Reduced conversion from carotenoids

• Drugs and alcohol

• Cholesterol lowering medication, laxatives, barbiturates

• Smoking and air pollution

• Excessive sun exposure

• Breaks down carotenoids in skin and retinal in eyes

(Zimmerman, 2001)

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Deficiency Symptoms

• Blindness

• Night blindness

• Xerophthalmia

• Xerosis

• Keratomalacia

• Bitot’s spots – May be artefact

of past deficiency

Keratomalacia

Bitot’s spots(motherchildnutrition.org)

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Deficiency Symptoms

• Impaired synthesis of red blood cells (Mejia 1986)

• Impaired iron mobilisation with increased stores and decrease in plasma iron (Mohanram 1981)

• Depressed immunity with increased infections

• Growth retardation

• Dry eyes (Sommer 2002)

• Impaired taste

• Balance disturbances (Heimburger 2006)

• Eggshell nails (Daniel 1985)

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Deficiency Symptoms

• Keratinization

• Rough, dry and scaly skin

• Perifollicular hyperkeratosis

on the lateral aspects of the

upper arms and the thighs (Heimburger 2006)

• Xerotic, wrinkled skin

covered with fine scales

‘toad skin’ (Ryan 1996)

Keratinization(Rolfes, Pinna and Whitney,

2009)

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Toxicity

• Hypervitaminosis A• Blurred vision, nausea, vomiting,

headaches (acute)

• Liver abnormalities (chronic)

• Reduced bone strength

• Birth defects• Neurological damage

• Physical deformities

• Increased lung cancer risk• In smokers with high dose beta

carotene supplementation

(McGuire 2011)

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Therapeutic Uses

• Chest infections

• Moderate vitamin A supplementation can improve outcomes and reduce reoccurance

(Biesalski and Nohr, 2003)

• Measles

• May be useful in preventing blindness associated with measles. (Semba and Bloem, 2004)

• Malaria

• In vitro studies show retinol acts against malaria parasite. (Hamzah et al, 2004)

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Therapeutic Uses

• HIV

• Low serum retinol increases the risk for mother-to-child transmission

• Vitamin A supplementation reduces mortality of HIV-positive children

(Humphrey et al, 2006)

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RDI

• Men: 900mcg/day RE

• Women: 700mcg/day RE

• Suggested Range: 1,000-15,000 mcg

• Note: UL 3000mcg RE/day

• Toxicity seen at 22,500 mcg RE/day

NHMRC 2009

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RDI

NHMRC 2009

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Activityo View the following video (15 mins)

‘Vitamin Grannies - Nepal’

http://www.youtube.com/watch?v=M2PgL7f9

sdE

o Discuss the implications of vitamin A deficiency and

programmes such as this in third world nations in

small groups then with the class.

o Online students should discuss within the online

discussion forum.

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Betacarotene and Carotenoids

• Serum carotene levels reflect recent intake

• b-carotene – carrots, broccoli, watercress, spinach,

apricots

• a-carotene

• Lycopene – tomatoes and processed tomato products

• Lutein – peas, spinach, dark-green leafy vegetables,

corn, egg yolk, kiwi fruit, grapes

• Zeaxanthin – corn, egg yolk, orange capsicum,

oranges, kiwi fruit

• Cryptoxanthin – mandarins, satsumas, apricots,

orange capsicum

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Functions

• Antioxidant

• Neutralises singlet oxygen and peroxyl radicals

• Lycopene is the most effective

• Works synergistically with Vitamin E

• Makes LDL more resistant to peroxidation

• Vitamin A production

• Anti-inflammatory – lycopene and lutein(Agarwal 2012)

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Therapeutic Uses

• CVD protection as antioxidants

• Astaxanthin and canthaxanthin, more so than

carotene carotenoids (Agarwal 2012)

• Cancer – lowered risk

• Breast (Borek, 2005)

• Prostate (Wertz et al 2004)

• Age related eye impairments

• Cataracts improved from lutein supplementation (Olmedilla et al, 2003)

• Macular degeneration (Stringham 2005)

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Toxicity

• Suggested Range –

15 -160mg

• Toxicity – Betacarotene has

no known toxicity

• Carotenemia (yellowing

of skin)

• >15mg must be prescribed

with an antioxidant, such as:

• Vitamin E

• Selenium

• Coenzyme Q10

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Review Questions

1. List the foods highest in Vitamin A

2. Outline the types of vitamin A and its derivatives.

3. What are the main functions of Vitamin A?

4. Which factors may increase the demand for

Vitamin A intake?

5. How might we recognise a Vitamin A deficiency?

6. What are some of the symptoms of vitamin A

toxicity?

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Activity

• Consider your vitamin A and beta-carotene intake from

the previous 2 diet diaries you have entered into your

diet analysis programme and answer the following

questions –

1. Are there any notable differences between the 24hour and 3

day average intake?

2. Would you recommend increased intakes from the RDI?

3. If so what is your rationale behind this? Think specific and

patient related and also from a more general context

4. Is there any specific dietary recommendations you would

make to optimise your intake? Include specific food choices

and quantities to reach your target.

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References• Agarwal et al 2012. Dynamic action of carotenoids in cardioprotection and maintenance of cardiac

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