Fat Soluble Vitamins

Vitamin

Essential organic compound required in small dietary amounts

Fat-soluble vitamins

Vitamin A D E K

Water-soluble vitamins

B-complex vitamins and vitamin C

Fat-soluble vitamin absorption

Requires bile acids and micelle formation

Chylomicrons

Transport fat-soluble vitamins from intestine to lymphatics

NPC1L1

Cholesterol transporter mediating uptake of vitamin D and E

SR-BI

Scavenger receptor transporting vitamins D E K

CD36

Fatty acid transporter involved in uptake of vitamins D and E

CRBP

Cellular retinol binding protein transporting vitamin A inside cells

Vitamin A forms

Retinol retinal retinoic acid

Retinol

Transport/storage form of vitamin A

Retinal

Visual pigment component for vision

Retinoic acid

Regulates gene transcription; irreversible form

Carotenoids

Plant pigments converted to vitamin A

β-carotene

Most important provitamin A carotenoid

Lutein and zeaxanthin

Carotenoids with non–vitamin A functions in eye protection

Vitamin A functions

Vision epithelial differentiation immunity reproduction

Vitamin A in vision

11-cis retinal + opsin → rhodopsin activation by light

Rhodopsin

Visual pigment activated when cis-retinal → trans-retinal

Retinoic acid receptors

RAR and RXR nuclear transcription factors

Vitamin A gene regulation

Controls >500 genes

Vitamin A absorption

Requires bile acids; retinol re-esterified and packed into chylomicrons

RBP

Retinol-binding protein that transports retinol in blood

TTR

Transthyretin stabilizes RBP-retinol complex

STRA6

Receptor mediating cellular retinol uptake

LRAT

Forms retinyl esters for storage in liver

Vitamin A deficiency causes

Poor diet fat malabsorption liver disease

Vitamin A deficiency symptoms

Night blindness xerophthalmia Bitot spots keratomalacia immune dysfunction

Xerophthalmia

Progressive drying and keratinization of eye

Vitamin A deficiency treatment

Oral or IM vitamin A supplementation

Vitamin A toxicity

Caused by excessive supplementation

Vitamin A toxicity symptoms

Teratogenicity bone loss dry skin liver injury GI symptoms

Hypercarotenemia

Benign orange skin discoloration from carotenoid excess

β-carotene cancer risk

High-dose supplementation increases lung cancer risk (CARET ATBC trials)

Vitamin D types

Vitamin D3 (cholecalciferol) and D2 (ergocalciferol)

Vitamin D3

Made in skin from UV light; found in animal foods

Vitamin D2

Plant/fungal form; used in supplements

Calcidiol

25-hydroxyvitamin D; major circulating form

Calcitriol

1

Vitamin D functions

Regulates Ca²⁺ and phosphate immunity and gene expression

Vitamin D receptor

VDR nuclear receptor that heterodimerizes with RXR

Vitamin D gene targets

≈250 genes involved in Ca transport and immunity

Vitamin D absorption

Requires bile acids and apical transporters NPC1L1 SR-BI CD36

Vitamin D deficiency causes

Low sun exposure dark skin malabsorption liver/kidney disease

Rickets

Childhood vitamin D deficiency causing bone deformities

Osteomalacia

Adult bone softening with pain

Osteoporosis

Low bone density with fracture risk but no bone pain

Vitamin D deficiency treatment

Vitamin D supplements diet sunlight

Vitamin D toxicity

Caused by excessive supplementation

Vitamin D toxicity symptoms

Hypercalcemia kidney stones soft tissue calcification nausea neurologic symptoms

Vitamin D safe sources

Food and sunlight DO NOT cause toxicity

Vitamin K forms

K1 phylloquinone; K2 menaquinone; K3 menadione (synthetic)

Vitamin K sources

Leafy greens and vegetable oils

Vitamin K functions

Coagulation (II VII IX X) and bone protein carboxylation

γ-carboxylation

Vitamin K-dependent modification enabling Ca²⁺ binding

Osteocalcin

Bone protein requiring vitamin K for activation

Matrix Gla protein

Vitamin K-dependent inhibitor of vascular calcification

Vitamin K absorption

Requires bile acids and SR-BI transporter

Vitamin K deficiency causes

Malabsorption biliary obstruction newborns

Vitamin K deficiency symptoms

Bleeding and elevated PT time

Vitamin K deficiency treatment

Parenteral vitamin K

Newborn vitamin K injection

Prevents hemorrhagic disease of newborn

Vitamin K toxicity

None known; safe even at high intake

Vitamin E forms

Tocopherols and tocotrienols (8 total)

α-tocopherol

Most active vitamin E form

Vitamin E sources

Nuts seeds vegetable oils leafy greens

Vitamin E function

Antioxidant preventing lipid peroxidation

Vitamin E works with vitamin C

Vitamin C regenerates oxidized vitamin E

Vitamin E absorption

Requires bile acids and NPC1L1/SR-BI/CD36

Vitamin E deficiency causes

Severe malabsorption abetalipoproteinemia

Vitamin E deficiency symptoms

Neuropathy ataxia myopathy hemolytic anemia

Vitamin E supplementation trials

Generally show no benefit and may increase cancer risk

Vitamin E toxicity

High doses increase bleeding risk by impairing vitamin K action

Vitamin E UL

1000 mg/day due to hemorrhagic stroke risk

Fat-soluble vitamin absorption summary

Requires bile micelles and transporters → chylomicrons → lymphatics

Fat-soluble vitamin deficiency common cause

Fat malabsorption (celiac Crohn pancreatic insufficiency cholestasis)

Fortified foods in US

Milk fortified with vitamins A and D