LeClaire Institute

Module 2 · Fat-Soluble Vitamins

Module 2 begins with the micronutrients: substances you need in milligrams or micrograms rather than grams. This lesson covers the four fat-soluble vitamins, A, D, E and K. All four are lipids built from five-carbon isoprene units, which is why they are absorbed with fat and stored in the body. Each is shown as a ball-and-stick model, with what it does, what happens with too little or too much, and where to find it in whole foods. The figure is on the left and the lesson script on the right; the quiz is at the end.

Previous lesson: Module 1 · Water and Ethanol

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Figure 1

The Fat-Soluble Vitamin Family Tree

A, D, E and K: four lipids you can’t make enough of.

What they share
Built mostly of carbon and hydrogenAll four are lipids, assembled from five-carbon isoprene units (Figure 2), so they dissolve in fat, not water.
Absorbed with fat, stored in the bodyThey need fat and bile to be absorbed and are stored in the liver and fat tissue (Figure 7). Stores last weeks to months, so you don’t need them every day.
Storage cuts both waysBecause they build up, large supplement doses of A and D can be harmful. Food sources almost never cause too much.
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Figure 2

Built from Isoprene

Why these four vitamins dissolve in fat, not water.

The building block

Isoprene, C5H8

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  1. 1Five carbons: a four-carbon chain with a one-carbon branch. Plants and animals join these units head to tail to build long, oily molecules.
Isoprene units, joined

Retinol (vitamin A), C20H30O

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  1. 1The ring and its first branches come from isoprene units, folded around.
  2. 2Four isoprene units in all: 20 carbons, with alternating single and double bonds along the chain.
  3. 3Just one OH group: too small a water-loving patch for 30 hydrogens of oily chain.

Compare glucose, with an OH on almost every carbon (Carbohydrates, Figure 3). Retinol is mostly C–H, like a fat, so it dissolves in oil, not water.

Fat-soluble versus water-soluble
Fat-soluble (A, D, E, K)Water-soluble (B group, C)
Made mostly ofcarbon and hydrogenmany O and N atoms, OH groups
Absorbedwith fat, via bile, into lymphdirectly into blood
Storedliver and fat tissue, for weeks to monthslittle storage (except B12); extra leaves in urine
Too muchpossible with supplements (especially A and D)less common, but possible for some (B6, niacin)

carbon hydrogen oxygen · every molecule on this page is drawn at the same scale with every hydrogen shown · tap one to enlarge it

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Figure 3

Vitamin A

Retinol, retinal and beta-carotene.

Vitamin A

Retinol and retinal

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Retinolthe form stored and carried

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Retinalthe form used in the eye

  1. 1Retinol ends in CH2OH.
  2. 2Remove two hydrogens and it becomes retinal, ending in CH=O. Retinal can be turned into retinoic acid, which switches genes on and off for cell growth.

Drawn straight (all-trans). In the eye, retinal sits bent at one double bond (11-cis) inside a protein; light straightens it, and that change is the first step of seeing.

What it is: Preformed vitamin A: retinol and the forms made from it (retinal, retinoic acid, and retinyl esters for storage).

In your body: Vision, especially in dim light; healthy skin and the linings of the eyes, gut and lungs; immune defense; growth and development.

Too little: Night blindness, then dry, damaged eyes; more infections. A leading cause of preventable blindness in children worldwide, though rare in the US.

Too much: Preformed vitamin A builds up in the liver. Large supplement doses can cause liver damage and, in pregnancy, birth defects. Adult upper limit: 3,000 µg a day of preformed vitamin A.

Found in: Liver (very high), fish liver oils, oily fish, eggs, butter, milk and cheese.

Beta-carotene, C40H56

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  1. 1The middle: a gut enzyme cuts here, and each half becomes retinal. So beta-carotene is provitamin A.
  2. 2Rings: the same ring as retinol, one at each end.

What it is: An orange plant pigment (a carotenoid) made of eight isoprene units.

In your body: Converted to vitamin A only as needed, so food sources don’t cause vitamin A poisoning. It takes about 12 µg of beta-carotene from food to make 1 µg of retinol activity (RAE).

Too much: Very large intakes turn the skin yellow-orange, which is harmless. High-dose supplements raised lung cancer risk in smokers in two large trials.

Found in: Carrots, sweet potato, pumpkin and squash, spinach and kale, cantaloupe, mango, apricots.

carbon hydrogen oxygen · every molecule on this page is drawn at the same scale with every hydrogen shown · tap one to enlarge it

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Figure 4

Vitamin D

Made in your skin from a cholesterol relative, then activated.

Vitamin D: made in your skin

7-Dehydrocholesterol

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↓ UVB sunlight, then body heat

Vitamin D3 (cholecalciferol), C27H44O

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  1. 17-Dehydrocholesterol is cholesterol with one extra double bond, here. Your skin has plenty of it.
  2. 2UVB light breaks the ring at this bond.
  3. 3The ring is now open: D3 is a secosteroid, a steroid with a broken ring. Same formula, C27H44O, nothing added.
  4. 4The OH from cholesterol survives. Two more OH groups are added later to make the active hormone.

Vitamin D2 (ergocalciferol), C28H44O

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  1. 1A double bond in the tail…
  2. 2…and one extra carbon. Otherwise the same as D3. Fungi and yeast make D2 from ergosterol when exposed to UV light.
From vitamin D to hormone
  1. Skin or foodD3 or D2 reaches the liver
  2. Liveradds an OH: 25-hydroxyvitamin D, the form blood tests measure
  3. Kidneyadds a second OH: calcitriol, the active hormone
  4. Gut and bonecalcitriol raises calcium and phosphate absorption and keeps bone mineralized
Vitamin D in brief
NeedsRDA 15 µg (600 IU) a day for ages 1 to 70, 20 µg (800 IU) over 70. Sunlight supplies a variable amount, depending on season, latitude, skin color and sunscreen.
Too littleSoft, weak bones: rickets in children, osteomalacia in adults; more risk of fractures in later life.
Too muchOnly from supplements, not sunlight: high blood calcium, nausea, kidney stones. Adult upper limit 100 µg (4,000 IU) a day.

Found in: Oily fish (salmon, trout, sardines, mackerel), cod liver oil, egg yolks, beef liver, and mushrooms exposed to UV light (D2). Few foods have much naturally, which is why milk and some other foods are fortified.

carbon hydrogen oxygen · every molecule on this page is drawn at the same scale with every hydrogen shown · tap one to enlarge it

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Figure 5

Vitamin E

The tocopherols, and how they protect cell membranes.

Vitamin E

Alpha- and gamma-tocopherol

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Alpha-tocopherolC29H50O2

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Gamma-tocopherolC28H48O2

  1. 1The OH on the ring head is the working part: it gives up its hydrogen to stop a chain reaction of damage.
  2. 2One methyl group: alpha has it, gamma has a plain H here. Only the alpha form is kept in the blood by the liver and counts toward your vitamin E needs.
  3. 3The tail anchors the molecule inside fatty cell membranes, right where it is needed.
How vitamin E protects membranes
  1. Damage startsa reactive oxygen molecule steals a hydrogen from a polyunsaturated fatty acid in a membrane
  2. Chain reactionthe damaged fatty acid attacks its neighbor, and so on
  3. Vitamin E steps inits ring OH hands over a hydrogen and stops the chain
  4. Recycledvitamin C and other antioxidants restore vitamin E

What it is: A family of eight related compounds (four tocopherols, four tocotrienols); alpha-tocopherol is the one your body uses to meet its needs.

In your body: The main fat-soluble antioxidant, protecting the polyunsaturated fats in cell membranes and in blood lipoproteins.

Too little: Rare, and mostly in people who can’t absorb fat: nerve and muscle damage, poor balance, weakened immunity.

Too much: Not from food. Supplements above the adult upper limit (1,000 mg a day) raise the risk of bleeding.

Found in: Sunflower seeds, almonds, hazelnuts, peanuts, wheat germ, sunflower and safflower oils, spinach. RDA 15 mg a day of alpha-tocopherol.

carbon hydrogen oxygen · every molecule on this page is drawn at the same scale with every hydrogen shown · tap one to enlarge it

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Figure 6

Vitamin K

Two forms, one working head: clotting and bone.

Vitamin K

Vitamins K1 and K2

K1 (phylloquinone), C31H46O2

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K2, menaquinone-4 (MK-4), C31H40O2

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  1. 1The head: a double ring with two C=O groups (a naphthoquinone). It is the same in every form of vitamin K and does the chemistry.
  2. 2K1’s tail: four isoprene units, only the first with a double bond. Plants make it in their leaves.
  3. 3K2’s tail: isoprene units that keep their double bonds. MK-4 has four; bacteria make longer ones, such as MK-7.
What vitamin K does
  1. Clotting proteins are madethe liver makes several clotting factors in an inactive form
  2. Vitamin K activates themit helps add an extra carboxyl group to certain amino acids
  3. Now they hold calciumand can gather at a wound to form a clot
  4. Also in bonethe same change activates proteins that bind calcium in bone

What it is: A family of naphthoquinones: K1 from plants and K2 (menaquinones) from bacteria and animal foods.

In your body: Needed to activate clotting proteins and some bone proteins. Adequate intake 120 µg a day for men, 90 µg for women.

Too little: Easy bleeding and bruising. Rare in adults; newborns get a vitamin K injection at birth because little crosses the placenta and breast milk is low in it.

Too much: No harm known from food or supplements, so there is no upper limit. People taking the blood thinner warfarin are advised to keep their vitamin K intake steady, because it counteracts the drug.

Found in: K1: kale, spinach, collards, broccoli, Brussels sprouts, lettuce, soybean and canola oils. K2: natto (fermented soybeans), cheese, egg yolks, chicken, liver.

carbon hydrogen oxygen · every molecule on this page is drawn at the same scale with every hydrogen shown · tap one to enlarge it

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Figure 7

Absorption, Storage and Labels

How they get in, where they are kept, and the forms on labels.

From food to storage
  1. Eaten with fata little fat in the same meal greatly improves absorption
  2. Bilemixes the vitamins with fats into tiny droplets (micelles)
  3. Gut wallthey are packed into chylomicrons with the fat
  4. Lymph, then bloodcarried around the body, then to the liver
  5. Storedvitamin A mainly in the liver; D and E in fat tissue and liver; K is used up fastest
Forms you will see
On the label or ingredient listWhat it isNotes
Retinyl palmitate, retinyl acetatevitamin A estersstable forms used in fortified milk and supplements
Beta-carotene (E160a)provitamin Aalso used as a yellow-orange color
Cholecalciferol, ergocalciferolvitamin D3, vitamin D2D3 is from animals (often lanolin); D2 from UV-treated yeast or mushrooms
d-alpha-tocopherolnatural vitamin Efull activity
dl-alpha-tocopheryl acetatesynthetic vitamin Eabout half the activity of the natural form
Tocopherols (E306–E309)vitamin E familyoften added as antioxidants to stop oils going rancid
Phylloquinone (phytonadione), menaquinone-7vitamin K1, K2K2 as MK-7 is common in supplements
Nutrition Facts Daily Values (adults)
VitaminDaily ValueUnit used
A900 µgµg RAE (retinol activity equivalents)
D20 µgµg; IU may also appear (1 µg = 40 IU)
E15 mgmg alpha-tocopherol
K120 µgµg
Reading the label
Only vitamin D is requiredSince the 2016 update, US labels must list vitamin D (with calcium, iron and potassium). Vitamins A, E and K are listed only when added or when a claim is made.
% Daily ValueThe DV is a single reference amount for labels; your own needs may be higher or lower.
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Figure 8

Where fat-soluble vitamins are used in the body

Tap a number on the cell to see what that part does; the list below it gives every other place in the body.

Vitamins A, D, E and K are absorbed with fat and stored, mostly in the liver and fat tissue.

Inside a cell

A typical animal cell, not to scale. Real cells hold thousands of ribosomes and hundreds of mitochondria.

Vitamins A, D, E and K work in membranes, the ER and the nucleus.

  1. Vitamin E sits among the fatty-acid tails and stops chain reactions of oxidation.
  2. The active forms of vitamin A (retinoic acid) and vitamin D (calcitriol) bind receptors that switch genes on.
  3. Vitamin K lets an enzyme here add an extra carboxyl group to clotting proteins and osteocalcin, so they can bind calcium.
  4. Liver enzymes here do the first step of activating vitamin D (to 25-hydroxyvitamin D).
  5. In the kidney, the second step makes active vitamin D (calcitriol).
  6. Vitamin A is stored as retinyl esters in droplets of the liver's stellate cells.

Everywhere else in the body

Each item, the places outside the cell where it is found or used, and what it does there.

Absorbing them

  • Small intestine. Absorbs A, D, E and K with fat, packed into chylomicrons.
  • Lymph. Chylomicrons carry them through the lymph before they reach the blood.

Vitamin A

  • Retina. Becomes retinal, the light-catching part of rhodopsin and the cone pigments; a shortage causes night blindness first.
  • Eye surface. Keeps the cornea moist and healthy; a severe shortage can scar it and cause blindness.
  • Liver. Stores most of it, in its stellate cells.
  • Blood. Carried on retinol-binding protein.
  • Skin and linings. Keeps the skin and the linings of the gut, lungs and urinary tract renewing.
  • Immune system. Needed for immune cells, especially in the gut.
  • Bones. Needed for growth; too much raises fracture risk.
  • Embryo. Guides how the body is laid out; too much in pregnancy causes birth defects.
  • Testes and ovaries. Needed to make sperm and for reproduction.

Vitamin D

  • Skin. Makes it in UVB sunlight.
  • Liver. Turns it into 25-hydroxyvitamin D, the form measured in a blood test.
  • Kidneys. Turn that into calcitriol, the active hormone.
  • Small intestine. Calcitriol makes it absorb calcium and phosphate.
  • Bones. Need it to harden; in a shortage, bones soften (rickets in children).
  • Parathyroid glands. Calcitriol tones down their hormone, PTH.
  • Fat tissue. Stores it.
  • Immune cells and muscle. Have vitamin D receptors; immune cells make some of their own calcitriol.

Vitamin E

  • Fat tissue. Holds most of the store.
  • Liver. Picks out alpha-tocopherol and sends it out in VLDL; other forms are cleared.
  • Blood. Carried in lipoproteins, where it protects LDL from oxidation.
  • Nerves. A long shortage damages nerves and balance.
  • Red blood cells. Protects their membranes from bursting.
  • Adrenal glands, pituitary and testes. Hold high levels.

Vitamin K

  • Liver. Makes clotting factors II, VII, IX and X, and proteins C and S.
  • Blood. Clots properly only with enough vitamin K; warfarin works by blocking it.
  • Bones. Activates osteocalcin, a bone protein that binds calcium.
  • Artery walls. Activates a protein (matrix Gla protein) that keeps calcium out of them.
  • Large intestine. Bacteria make vitamin K2.
  • Newborns. Born with little, so they get a vitamin K shot at birth.
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Figure 9

Putting It All Together

The whole lesson in one table, plus a few extras.

The four fat-soluble vitamins
VitaminMain formsMain jobToo littleToo muchWhole-food sources
Aretinol, retinal; beta-carotenevision, skin and linings, immunitynight blindnessliver damage, birth defects (preformed A)liver, eggs, dairy; orange and green vegetables
DD3, D2calcium absorption, bonerickets, osteomalaciahigh blood calcium (supplements)oily fish, egg yolks, UV mushrooms; sunlight
Ealpha-tocopherolantioxidant in membranesnerve damage (rare)bleeding risk (supplements)seeds, nuts, wheat germ, plant oils
KK1, K2activates clotting and bone proteinsbleedingnone knownleafy greens; natto, cheese, eggs
Worth knowing

Eat colorful vegetables with a little fat

Carotenoids and vitamin K from vegetables are absorbed much better with some oil, nuts or other fat in the meal.

Liver is the richest source of vitamin A

A typical serving of beef liver has several times the adult RDA, so it is best eaten occasionally, especially in pregnancy.

Sun and vitamin D

Skin stops making more vitamin D once enough has formed, so sunlight can’t cause vitamin D poisoning; supplements can.

Cholesterol’s relatives

Vitamin D is made from a cholesterol precursor, and A, E and K are built from the same isoprene units as cholesterol (Lipids, Figure 3).

General education, not medical advice. Facts follow mainstream sources (US Dietary Guidelines, NIH Office of Dietary Supplements, standard biochemistry and food-science texts).

Quiz

Tap a question to see the answer

1. Why do vitamins A, D, E and K dissolve in fat rather than water?

They are made mostly of carbon and hydrogen (built from isoprene units), with few OH groups (Figure 2).

2. What is isoprene?

A five-carbon building block, C5H8, that plants and animals join to make molecules like retinol and carotenoids (Figure 2).

3. What is the difference between retinol and retinal?

Retinol ends in CH2OH; retinal ends in CH=O (two hydrogens fewer) (Figure 3).

4. Why is beta-carotene called provitamin A?

The body can cut it in the middle and turn each half into retinal (Figure 3).

5. Why is preformed vitamin A a concern in pregnancy?

Large amounts, mainly from supplements or lots of liver, can cause birth defects (Figure 3).

6. What does UVB light do to 7-dehydrocholesterol in the skin?

It breaks open the second ring, forming vitamin D3 (Figure 4).

7. Where is vitamin D activated?

An OH is added in the liver, then a second in the kidney, making calcitriol (Figure 4).

8. Name two deficiency diseases of vitamin D.

Rickets in children, osteomalacia in adults (Figure 4).

9. What part of vitamin E does the antioxidant work?

The OH on its ring head, which gives up a hydrogen to stop a chain reaction (Figure 5).

10. How do alpha- and gamma-tocopherol differ?

Gamma lacks one methyl group on the ring; only alpha counts toward vitamin E needs (Figure 5).

11. Why do newborns get a vitamin K injection?

Little vitamin K crosses the placenta and breast milk is low in it, so babies risk bleeding (Figure 6).

12. Which vitamin must be listed on every US Nutrition Facts label?

Vitamin D (Figure 7).

Next lesson: Module 2 · Water-Soluble Vitamins →