8.1: Fat-Soluble Vitamins

Fat-soluble vitamins (vitamins A, D, E, & K) all share similar characteristics (Figure 8.1). As micronutrients, small amounts of the fat-soluble vitamins daily are necessary for optimal health. They can often be found in the fatty portions of foods, but are also present in a wide variety of plantand animal-based foods. The digestion of fat-soluble vitamins requires the presence of dietary lipids as well as the action of bile for breakdown. Fat-soluble vitamins are absorbed in the small intestine, and once absorbed, they are circulated to the lymph by chylomicrons prior to eventually entering the blood. Toxicity can be a concern with these vitamins, as the body can store the fat-soluble vitamins. Therefore, consuming large amounts of them, particularly through supplementation, can result in toxicity.

Figure 8.1 Fat-soluble vitamins share some common characteristics. Image by Author.

Table 8.1 Characteristics of fat-soluble and water-soluble vitamins.

Category	Vitamins	Key Functions	Characteristics
Fat-Soluble	A, D, E, K	-Vision (A) -Bone health (D) -Antioxidant (E) -Blood clotting (K)	-Stored in liver and adipose -Risk of toxicity if consumed in excess
Water-Soluble	B-complex, C	-Energy metabolism (B vitamins) -Red blood cell formation (B12, folate) -Collagen synthesis, immune support (C)	-Not stored in large amounts -Excess excreted in urine -Must be consumed regularly

Vitamin A

Vitamin A consists of a family of compounds called retinoids. Retinoids are also referred to as preformed vitamin A and include retinol, retinal, and retinoic acid. The body is able to convert retinol to retinal in a reversible fashion, and retinal to retinoic acid in an irreversible manner. The vitamin A family also includes carotenoids — provitamin A and nonprovitamin A carotenoids. Provitamin A carotenoids can be converted to vitamin A. For example, beta-carotene is one of the most common provitamin A carotenoids found in food and can form two molecules of retinal. Nonprovitamin A carotenoids cannot be converted into vitamin A, but are still beneficial for health even though they don’t contribute to vitamin A levels. For example, lycopene is a nonprovitamin A carotenoid found in red fruits and vegetables and is known for its beneficial antioxidant properties.

Retinoids are mainly found in animal foods, while provitamin A carotenoids are found mainly in plants. Retinol activity equivalent (RAE) is used to describe the overall vitamin A content of foods since there are these various forms of vitamin A, each with its own biological potency. RAE makes it possible to compare the nutritional content of foods containing preformed vitamin A to foods with provitamin A carotenoids.

Dietary Sources

The RDA for vitamin A is 700 µg RA/day for women and 900 ug RAE/day for men. Preformed vitamin A is found in animal products such as liver and organ meats, eggs, fatty fish, and dairy. Provitamin A carotenoids are frequently found in orange and dark green retables such as carrots, sweet potatoes, spinach, and kale (Figure 8.2).

Figure 8.2 Examples of food sources of vitamin A. Image from R3genHealth is licensed under CC BY-NC 4.0.

Important Roles

Vitamin A is important in supporting vision, immune function, reproductive health, and cellular growth and differentiation. It also helps maintain healthy skin and mucous membranes.

Vitamin A is essential for vision, particularly in low light conditions. When light enters the eye, it strikes the rod and cone cells that make up the retina at the back of the eye (Figure 8.3). Vitamin A is essential for the production of rhodopsin, a pigment in the rod cells of the retina that allows us to see in low light. Specifically, retinal and the protein opsin combine to form rhodopsin. Night blindness is a common symptom of Vitamin A deficiency because the eye cannot produce enough rhodopsin for proper function in the dark.

Figure 8.3 Rod and cone cells in the retina allow us to see color and black and white, respectively. Rod cells are important for night vision, consisting of a rhodopsin pigment that contains retinal. Image on the left by Cenveo is licensed under a Creative Commons Attribution 3.0.Cropped Image on the right by Elizabeth D. Kirby, Melissa J. Glenn, Noah J. Sandstrom, Christina L. Williams, OpenStax from Introduction to Behavioral Neuroscience (2024) is licensed under CC BYSA 4.0.

Vitamin A is also important for cellular growth and differentiation, and the maintenance of healthy skin and mucous membrane barriers. Retinoic acid is specifically important for cell differentiation, as it up regulates genes that encode for proteins that cause a cell to differentiate into an epithelial cell. Old epithelial cells are constantly sloughed off, such as in the gastrointestinal tract and skin, so a steady supply of vitamin A is needed to make new epithelial cells. This is important in the maintenance of our protective barriers.

Consequences of Deficiency or Toxicity

Vitamin A deficiency — caused by inadequate vitamin A intake or impaired vitamin A utilization by the body — is the leading cause of preventable blindness in children worldwide. It leads to a spectrum of ocular issues, known as xerophthalmia, that can cause anything from dryness of the eyes to potential vision loss. Given the importance of vitamin A in the rhodopsin molecule of the rod cells, one of the initial symptoms of vitamin A deficiency is often night blindness, where individuals have difficulty seeing in low light conditions. More severe vitamin A deficiency can lead to dry and damaged conjunctiva (the membrane lining the eyelids and white part of the eye), drying, ulceration, and scarring of the cornea (outer layer of the eye), or the accumulation of dead cells on the surface of the eye (known as Bitot’s spots).

Vitamin A deficiency can cause a range of skin problems as well, including dryness, itching, and scaling. Vitamin A is crucial for skin cell growth and repair, so it’s deficiency can lead to the aforementioned symptoms as well as impair the skin’s ability to heal, increasing susceptibility to infections and inflammation.

While getting adequate vitamin A in our daily diet is essential for health, it is also important to avoid excessive intake. Chronic consumption of 3-4x the RDA can lead to hypervitaminosis A. This occurs when the body has too much vitamin A, usually from excessive supplementation or very high intake of foods rich in preformed vitamin A, such as liver. Symptoms often include headaches, blurred vision, liver abnormalities, and decreased bone strength. Carotenodermia can also result from the chronic overconsumption of carotenoids, and this typically results in the skin becoming yellow-orange in color.

Health Note

Vitamin A is important for vision, immunity, and skin health.

Fun Fact

The “A” in Vitamin A could stand for “Animal and Orange”—it’s found in liver and carrots!

Vitamin D

Vitamin D is considered both a nutrient and a prohormone — a nutrient because it is found in food, and a prohormone because the body uses it to produce an active hormone. There are two dietary forms of vitamin D: ergocalciferol (vitamin D2) found in plant sources and cholecalciferol (vitamin D3) found in animal sources. Vitamin D3 is also the form of vitamin D made in the body.

Vitamin D is known as the sunshine vitamin, as exposure of the skin to ultraviolet rays from sunlight converts a cholesterol metabolite (7- dehydrocholesterol) to previtamin D3 (precalciferol). In the skin, previtamin D3 is then converted to vitamin D3 (cholecalciferol). Vitamin D3 then diffuses into the blood and circulates to the liver. Vitamin D3 is then further metabolized and converted to 25- hydroxyvitamin D in the liver, and this is converted to calcitriol in the kidneys. Calcitriol is the active form of vitamin D in the body (Figure 8.4).

Figure 8.4 Synthesis of vitamin D. Figure 6.22 byJ. Gordon Betts, Kelly A. Young, James A. Wise, Eddie Johnson, Brandon Poe, Dean H. Kruse, Oksana Korol, Jody E. Johnson, Mark Womble, Peter DeSaix, OpenStax from Anatomy and Physiology 2e (2022) is licensed under Creative Commons Attribution 3.0 Unported license.

Dietary Sources

The RDA of vitamin D for both women and men is 15 µg/day. Though vitamin D is not found naturally in a large amount of foods, it can be found in dietary sources such as fatty fish, cod liver oil, whole milk, and egg yolks. The most common sources of vitamin D are foods fortified with it, such as dairy products like milk, cereals, and orange juice (Figure 8.5).

In addition to being consumed through the diet, Vitamin D is unique because the body can synthesize it when the skin is exposed to ultraviolet B rays from sunlight. The resulting vitamin D3 is chemically the same as what is consumed from animal foods. For the body to produce vitamin D, it is suggested that people have approximately 5-30 minutes of midday sun exposure at least two times per week to the face, arms, legs, or back. Many environmental, genetic, and lifestyle factors can influence how much vitamin D a person can make endogenously. Therefore, people with darker skin or those who live in persistent smog or overcast skies may require additional sun exposure to make adequate vitamin D.

Figure 8.5 Vitamin D-rich food sources include items such as fatty fish, dairy, eggs, and mushrooms. We can also get vitamin D from the sun! Image by pch.vector and designed by Freepik.

Important Roles

Vitamin D is essential for calcium and phosphorus absorption, which supports the development and maintenance of strong bones and teeth. Unlike most vitamins, vitamin D functions more like a hormone, with receptors found in nearly every cell of the body.

Calcium needs to always be available to the body’s tissues. Not only is calcium the primary mineral component of our bones providing the structural foundation of our bodies. It is also for processes such as muscle contraction, blood pressure regulation, and conduction of neural impulses. Vitamin D (calcitriol) is crucial for maintaining healthy levels of calcium in the blood, by modifying activity at the small intestine, kidneys, and bone.

If blood calcium levels were low, this would result in increased vitamin D activation in the kidneys. The following would then occur to raise blood calcium concentration:

• Small intestine —calcitriol upregulates genes that code for calcium transport proteins, allowing for absorption of calcium.
• Kidneys — calcitriol and parathyroid hormone (PTH) cause the kidneys to reduce excretion of calcium into the urine.
• Bone — calcitriol and PTH stimulate activity of osteoclasts, cells responsible for breaking down bone, and calcium is released from the bone into the blood.

In a condition of hypercalcemia, where blood calcium levels are too high, the opposite would occur — absorption in the small intestine would decrease, kidneys would excrete more calcium, and osteoclast activity in the bone would be inhibited.

Consequences of Deficiency or Toxicity

Vitamin D deficiency is relatively common, especially in individuals with limited sun exposure, darker skin, older age, or fat malabsorption disorders. It is estimated that more than 1 billion people worldwide have insufficient levels of vitamin D. Deficiency can lead to inadequate bone mineralization during early life and increased demineralization of bone later in life.

Vitamin D deficiency can lead to rickets in children. Rickets is a result of improper bone mineralization, leading to soft and deformed bones. Long bones cannot support the stress of weight-bearing activities, and result in characteristically bowed legs and/or slower growth. In adults, vitamin D deficiency results in osteomalacia and osteoporosis. Osteomalacia often causes diffuse bone pain and muscle weakness as a result of soft and weak bones. Osteoporosis involves the demineralization of previously healthy bone, making it overall weaker and more prone to fracture (Figure 8.6). Due to this risk, the RDA for vitamin D increases to 20 µg/day for individuals over the age of 70.

Figure 8.6 Osteoporosis due to increased demineralization of healthy bone leads to bones with thin walls and large spaces. Image by goelsewhere on Flickr is licensed under a CC BY-NC 2.0 license.

Vitamin D toxicity is rare but can occur with excessive supplementation. Because of vitamin D’s role in calcium absorption, excretion, and mobilization, chronic high levels of vitamin D leads to high calcium levels in the blood and urine. This may cause nausea, vomiting, weakness, kidney stones, and calcification of soft tissues like the heart and lungs.

Health Note

Vitamin D helps the body absorb calcium and supports immune health.

Fun Fact

Your skin can make vitamin D when exposed to sunlight—it’s the only vitamin your body produces from a non-food source!

Vitamin E

Vitamin E is a group of eight different compounds related in molecular structure, of which alpha-tocopherol is the most biologically active compound. Vitamin E acts as an antioxidant, helping to protect cell membranes from oxidative damage from reactive oxygen species. It also supports immune function and helps maintain healthy skin and eyes.

Dietary Sources

The RDA for vitamin E is 15 mg/day for both women and men. Vitamin E is particularly abundant in vegetable oils, nuts, seeds, leafy greens, and fortified cereals (Figure 8.7).

Figure 8.7 Examples of food sources of vitamin E. Image modified from photo by Towfiqu barbhuiy on Pexels.

Important Roles

Free radicals are unstable molecules because they have unpaired electrons in their outer shells. They are capable of damaging (oxidizing) fatty acids in the phospholipid bilayers of cell membranes. Vitamin E plays an important role in acting as an antioxidant and protecting biological membranes. Vitamin E does so by donating electrons to free radicals, thereby stabilizing them and preventing them from damaging the fatty acids embedded in membranes (Figure 8.8).

Vitamin E may also help to prevent the formation of cataracts, an opacity of the normally clear lens of the eye. Smokers and individuals exposed to excessive amounts of sunlight are at an increased risk of cataract formation due to free radical damage. Increased vitamin E consumption through the diet or supplementation may decrease the risk of developing cataracts, particularly in more at-risk populations.

Figure 8.8 An antioxidant, such as vitamin E, is able to donate an electron to stabilize a free radical and prevent oxidative damage from that free radical. Image by Lobo et al. (2010) is licensed under the Creative Commons Attribution Share-Alike 4.0 International license.

Consequences of Deficiency or Toxicity

Deficiencies in vitamin E are rare, and are typically reported in people who have an underlying condition that impairs fat absorption and/ or the absorption of fatsoluble vitamins. Deficiency may result in muscle weakness, vision issues, nerve damage causing numbness and tingling, and a weakened immune system. Hemolytic anemia may also occur as a result of a vitamin E deficiency, due to weakened and ruptured red blood cells. This is likely due to the lack of vitamin E available to protect red blood cell membranes from oxidative damage. This ultimately leads to the cells breaking down, diminishing their capacity to carry oxygen and causing weakness and fatigue.

Vitamin E toxicity is rare, as the tolerable upper limit is 1,000 mg/day. High-dose supplementation can increase the risk of bleeding, as it can interfere with blood clotting. This is especially true for individuals also taking blood thinners.

Health Note

Vitamin E acts as an antioxidant, protecting cells from damage.

Fun Fact

Vitamin E helps keep your skin youthful by fighting free radicals.

Vitamin K

Vitamin K is a family of structurally similar compounds. Phylloquinone (vitamin K1) is found in plant foods. Vitamin K1 is also found in some supplements and is given to infants at birth to prevent bleeding. Menaquinone (vitamin K2) is found in fermented foods and some animal products. It is also produced in small amounts by bacteria in the large intestine. Menadione (vitamin K3) is produced commercially. Interestingly, vitamin K was discovered by physiologist Henrik Dam when he determined that vitamin K deficiency in chickens caused excessive bleeding.

Dietary Sources

The Adequate Intake level established for vitamin K is 90 µg/day for women and 120 µg/day for men. Vitamin K is found mainly in leafy green vegetables (such as kale, spinach, and broccoli) (Figure 8.9), vegetable oils, and fermented foods. It is also produced in small amounts by gut bacteria.

Figure 8.9 Examples of food sources of vitamin K. Modified from Image by Viktoria Slowikowska from Pexels.

Important Roles

Vitamin K is essential for blood clotting (coagulation). It acts as a cofactor for enzymes that modify clotting factors produced in the liver, enabling them to bind calcium and initiate the clotting cascade. The coagulation process is like a row of dominoes — the last one won’t fall if the others haven’t fallen in sequence. Vitamin K activating clotting factors allows the next reaction in the cascade to occur where the clotting factors convert prothrombin to thrombin. Thrombin then catalyzes the conversion of fibrinogen (water-soluble protein) to fibrin (waterinsoluble protein). Fibrin forms a web-like clot to stop bleeding. Without vitamin K, the body would not be able to produce enough activated clotting factors, leading to impaired blood clotting and increased risk of bleeding.

Consequences of Deficiency or Toxicity

Vitamin K deficiency is rare in adults, though can occur in individuals with fat malabsorption disorders, those on long-term antibiotics, or people taking medications that interfere with vitamin K activity. Long-term use of antibiotics can kill bacteria in the large intestine that produce vitamin K, while anticoagulants such as warfarin that are prescribed to prevent blood clots in individuals with cardiovascular disease, decrease the activity of vitamin K. Symptoms of vitamin K deficiency typically include easy bruising, excessive bleeding, or hemorrhage.

Vitamin K deficiency does occur in some infants and can be life-threatening with uncontrolled internal bleeding (vitamin K deficiency bleeding, VKDB). Furthermore, infants are born with low stores of vitamin K, lack vitamin Kproducing bacteria at birth, and human milk contains low levels of vitamin K. For these reasons, the American Academy of Pediatrics recommends a vitamin K injection be routinely given at birth to avoid VKDB.

Health Note

Vitamin K is essential for blood clotting and bone health.

Fun Fact

Newborns get a vitamin K shot because they don’t have enough gut bacteria to make it yet.