Fat-Soluble Vitamins

Properties of fat-soluble vitamins

• lipid soluble

• absorbed in the presence of fat (if we take a fat soluble vitamin, we must also eat it with fat or else we can’t absorb a lot of it)

• absorption/transport is similar to that of fat

• can be stored (liver, adipose mostly)

• can be toxic in high doses

what is the other name for vitamin E?

alpha-tocopherol (toco- means childbirth and pher- is to bear)

what is the function of vitamin E?

antioxidant

Vitamin E discovery and history

• Bishop and Evans needed a fat soluble factor that prevented fetal reabsorption in rats

• they discovered that vitamin E helps prevent unsaturated fats from oxidizing

Vitamin E absorption, transport, and excretion

• absorbed with fats (emulsification with bile acids)

• incorporated into chylomicrons for circulation

• processed in the liver

• excretion via bile and feces

• can also be excreted through the urine, but only after being processed in the liver

alpha-tocopherol significance in digestion

acts as the transfer protein

Vitamin E RDA and UL

RDA: 15 mg/day for adults (alpha-tocopherol form only)

UL: 1000 mg/day

Vitamin E deficiency symptoms

vitamin E deficiency is very rare (usually caused by insufficient fat absorption)

symptoms:

• retinopathy

• peripheral neuropathy (myelin sheath impairment)

• ataxia (myelin sheath impairment)

• lower immune function (due to membrane impairment)

Foods rich in vitamin E

• vegetable oils

• can be destroyed with heat and oxidation

Vitamin E toxicity

Not well researched

• possible interference with blood clotting

• Very rare

What family of compounds does vitamin A encompass?

Retinoids

Vitamin A functions

• light absorbing pigment in the eye (rhodopsin)

• Regulation of gene expression (nuclear receptors, meaning they get into nucleus and bind to DNA)

What is rhodopsin and what is its significance?

Rhodopsin is a light-absorbing pigment

It’s for the rod cell photoreceptors at the back of the retina

• helps us see in low light

Retinal/retinol cycle

11-cis retinal + opsin = rhodopsin

• breaks down in response to light (photo-bleaching): all trans-retinal and opsin

• Opsin is responsible for the neuronal signals of vision

• We need to regenerate 11-cis retinal to make rhodopsin

Review the visual cycle slide

What is the active form of vitamin A?

Retinoic acid

Retinoic acid production and function

• produced in small amounts locally in many tissues

• Retinoic acid receptors and Retinoid X receptors

Regulates:

• cell differentiation

• Growth

• Embryonic development

• Reproduction

• Immunity

Review slide 16 for what we need to know for the exam

Vitamin A discovery history

• discovered at UW- Madison by McCollum and Davis in 1913

• Vitamin A was the lipid soluble factor needed to support growth in rats

Dietary sources of Vitamin A

• animal products (retinyl esters)

• Liver (polar bear liver has a toxic dose of vitamin A)

• Dairy products

• Egg

• Fish (tuna, herring, sardines)

• Fortified foods (margarine, cereals)

• Foods with carotenoids (a plant pigment found in fruits and vegetables like carrots and sweet potatoes)

What structures can be converted into vitamin A by our bodies?

• beta-carotene (found in sweet potatoes and carrots)

• Alpha-carotene

• beta-cryptoxanthin

Conversion of pro-vitamins

• conversion of beta-carotene requires the enzyme BCO1 (beta-carotene oxygenase 1)

• Converts beta-carotenes to retinal (one molecule of beta-carotene produces 2 molecules of retinal)

• 12 mcg beta-carotene yields 1 mcg retinol

In what body part is BCO1 most abundant in?

Epithelium in small intestine

Vitamin A absorption

Vitamin A as retinyl esters is sufficiently absorbed in the small intestine as long as enough fats are present

Cooking foods with vitamin A in fat increases absorption

Absorption of carotenoids (pro-vitamin A) is lower

• for raw veggies, it can be low as 5%

• Less absorption=less likely to experience toxicity

What happens once vitamin A is absorbed?

Retinol and beta-carotene are metabolized in the enterocytes before entering the bloodstream (review slide 22, 23, 24)

Vitamin A RDA

Men: 900 microgram RAE

Women: 700 microgram RAE per day

• pregnant: 770 microgram RAE

• lactating: 1300 microgram RAE

Tolerable upper intake level: 3000 microgram RAE

Know what RAE actually means! Everyone needs the same amount but different amounts may vary based on source

People who are vegetarians only get it from vitamin A conversion, so they may need to consume more of that source than meat eaters

Vitamin A deficiency symptoms

mostly an issue in developing countries

Night blindness

• inability to adapt to darkness

• Often the first sign of vitamin A deficiency

• Consequence of diminished ability to regenerate rhodopsin (rod cells)

• Crude indicator of vitamin A deficiency

Xerophthalmia

• excessive dryness of eye caused by mucus production

• Leads to corneal and conjunctival scarring, blindness

Bitot spots

white accumulations of sloughed cells and secretions

poor growth

Increases susceptibility to infection

• vitamin A is needed for immunity

Vitamin A toxicity

Acute

• can result from excessive dose- leads to nausea, vomiting, double vision, and headache

Chronic

• develops over months to years (3-4x RDA may be toxic)

• anorexia

• Hair loss

• Skin issues

• Increased bone fractures

• Eye pain

• Liver damage

• Birth defects (accutane- pregnant women shouldn’t use this)

what chemical group is vitamin K a part of?

quinones

from what term does the “K” in vitamin K come from?

koagulation

Vitamin K function

• primary for blood clotting

• essential for the activation of several proteins that participate in the clotting process

• participates in bone calcification

Vitamin K gamma-carboxylation

we tend to recycle vitamin K, so there isn’t much stored

• clotting factors like Thrombin require the ability to bind the Ca2+ to be active

• gamma carboxylation provides this ability

Vitamin K’s interaction with Warfarin

warfarin was previously used as a blood-thinner (not really used anymore).

Warfarin interferes with the recycling of vitamin K, which makes it less available and reduces gamma-carboxylation clotting factors

vitamin K discovery

by Henrik Dam and Edward A Doisy

• discovered by feeding fat-free diets to chickens and saw that they suffered from a hemorrhagic disease

how is vitamin K absorbed?

• absorbed in the small intestine

• requires fat/bile and pancreatic factors

• supplement forms are more readily absorbed than what comes from food

How is vitamin K transported around the body?

• transported by chylomicrons

• unlike other fat-soluble vitamins, our storage is limited

• we use reducing power from NAD(P)H to recycle vitamin K

vitamin K intake recommendations

Adequate intake (different from RDA):

men: 120 micrograms a day

women: 40 micrograms a day

• gut bacteria also appear to be able to synthesize vitamin K, although the amount bioavailable and absorbed by us in unclear

toxicity symptoms are not known

those who are using blood thinners need a consistent amount of vitamin K (eating it one night and never again is not enough)

vitamin K food sources

green, leafy vegetables

• spinach

• kale

• broccoli

gut bacteria

• likely insufficient amounts to meet needs

vitamin D history

has a long history with UW-Madison

• started with Henry McCollum, then Henry steenbuck, and now there are current professors at Madison researching the functions of vitamin D

vitamin D food sources

• beef

• veal

• eggs

• fatty fish (salmon, herring, tuna)

• liver

• the sun (15 minutes of direct exposure to the sun is said to be enough vitamin D for our bodies)

• fortified foods (milk/dairy, orange juice, breads and cereals)

vitamin K absorption

absorption from foods

• is roughly 50% efficient

• occurs in he distal ileum of the small intestine

• requires bile acids and fat

• incorporated into mixed micelles

• packed into chylomicron for circulation

later circulations bound to vitamin D binding protein

vitamin D synthesis

vitamin D is synthesized by the skin

• produced the majority of vitamin D from sun exposure (which is why it is recommended that those living in northern latitudes— Wisconsin being one of them— is recommended that they take vitamin D supplements, especially in the winter)

• affected by: the amount of UVB radiation, age, race, clothing, sunscreen use

• cholecalciferol (vitamin D3) enters bloodstream bound to vitamin D binding protein

vitamin D activation/regulation

vitamin D is a two-step activation process

liver: 25-Ohase (inactive)

+

kidney: 1 alpha-Ohase (inactive)

=

final product: 1,25-(OH)2D3 (calcitrol)- this is the active form of vitamin D

• this regulates its own breakdown (negative feedback)

when considering supplements, the patient’s function of the kidney and liver is important because people need the active form

vitamin D function

to maintain normal serum calcium and phosphorus levels in the blood (review slides 21 and 22- 23 is the the most important)

Vitamin D and bone health

calcitrol (active vitamin D) facilitates calcium absorption from the gut, which is needed for bone mineralization

increases expression of cal binding and calcium channels

similar effects on tubules to increase calcium reabsorption from urine

Vitamin' D’s involvement in gene expression

• behaves as a hormone (same as vitamin A) and regulates gene expression by binding the vitamin D receptor (VDR)

• VDR is expressed in most cell types, suggesting broad functions (nuclear receptor)

• Through its action on gene expressions, vitamin D influences immune response and host-defense against pathogens via CAMP (prevents us from getting sick)

vitamin D daily intake requirements

RDA: 600 IU (indicates that there are many ways to get vitamin D) (15 micrograms) for most age groups

• prevents deficiency for bone health

• older adults (over 50 years): 800 IU a day (20 micrograms)

  • reduced sun exposure

  • reduced skin biosynthesis

  • reduced kidney activity

• RDA is not different for pregnant or lactating women

• tolerable upper intake level: 4000 IU/day (lower for kids)

requirement can be met with 15 minutes of direct sunlight a day, but highly variable depending on sunscreen use, clothing, time of day, etc.)

Vitamin D deficiency symptoms

• inadequate calcium ad phosphorus deficiency in the bone

• osteomalacia (soft bones- occurs in adults)

  • may be caused by kidney, stomach, gallbladder, intestinal, or liver disease affecting vitamin D absorption or metabolism

  • treatment: sun exposure, supplements)

• rickets (occurs in children)

  • bowed legs, enlarged head and rib cage, and deformed pelvis (this was fairly common in the 1900s because the Industrial Revolution led to a lot of air pollution, resulting in everyone getting lower exposures of vitamin D from the sun)

vitamin D toxicity symptoms

toxicity from sun exposure or foods is unlikely/impossible

tolerable upper intake level: 4000 IU/day

toxicity is most likely to result from excessive supplementation

• hypercalcemia

• kidney dysfunction

• loss of appetite

• GI stress