3.1 Vitamins

Vitamins A, D, E, and K

Fat-soluble vitamins include vitamins A, D, E, and K. Fat-soluble vitamins play essential roles in many physiological processes, such as vision, bone health, immune function, and blood clotting (Reddy & Jialal, 2022). Fat-soluble vitamins, like dietary fat, are absorbed through the lymphatic system and then released into the blood, carried by transport proteins. Because these vitamins are stored, daily intake is not required. Excess intake of fat-soluble vitamins, as found with some supplements, can cause toxicity—side effects from taking large doses of supplements or medications.

Absorption of fat-soluble vitamins occurs in the small intestine where they are mixed with bile salts, fatty acids, and phospholipids; absorbed by chylomicrons (microproteins); and carried to the lymphatic system. Since all vitamins require carrier proteins for transportation across the lipid bi-layer, absorption can be affected adversely by a genetic abnormality in the transport molecules (Ofoedu et al., 2021).

Vitamin A is active in the genetic development of retinol pigments and contributes to healthy bones, teeth, and soft tissue. Vitamin A also plays a role in reproduction, facilitating semen production and cell differentiation in fetal development. Vitamin A is critical in immune function, helping to grow the cells that produce the mucus that lines the gastrointestinal tracts, sinuses, and genitourinary tract. This mucus traps and protects the human body from the myriad bacteria it encounters daily. Beta-carotene—a precursor to vitamin A—is an antioxidant that protects against certain cancers and aging by stabilizing free radicals; a free radical is an unstable molecule made during normal cell metabolism that has one unpaired electron (Figure 3.2).

Figure 3.2 An antioxidant stabilizes a free radical by donating an electron to the unpaired electron of the free radical. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

Vitamin D is a fat-soluble vitamin that closely resembles a hormone’s functions. This vitamin can trigger effects in tissue throughout the body, turning on and off the production of proteins. Vitamin D, like vitamin A, plays a role in immunity by promoting the secretion of infection-fighting substances found in white blood cells (Dimitrov et al., 2021).

Vitamin D naturally occurs in some foods (fatty fish and egg yolks), is added to others (like milk and orange juice), and is available as a vitamin supplement. Vitamin D is unusual because the body can synthesize it from a cholesterol precursor—7-dehydrocholesterol (7-DHC)—in the epidermis with the help of ultraviolet light. In addition, vitamin D assists in promoting calcium uptake in the gut and ensures adequate calcium and phosphorus for bone mineralization. Bones can become thin, fragile, and deformed without sufficient vitamin D. Vitamin D prevents rickets, the softening of the bones, which results in bowed legs, and protects against osteoporosis, the loss of bone density, which leads to porous structure (National Institutes of Health [NIH], 2023e).

Vitamin E, a fat-soluble vitamin, acts as an antioxidant and stops the development of free radicals during fat oxidation. Fat oxidation is a chemical reaction in which a healthy molecule loses or is robbed of one of its electrons, which then produces an unhealthy free radical. In addition to protecting the cell from reactive oxygen species (ROS) (reactive species capable of causing damage to biomolecules), vitamin E helps establish a robust immune system and improves the endothelial cells on the surface of blood vessels, making them more resistant to the adherence of clots (NIH, 2021c).

Many other claims about vitamin E exist; however, due to the difficulty in establishing biomarkers and correlating them with clinical outcomes, recommendations for vitamin E intake continues to emerge (Institute of Medicine [U.S.] Panel on Dietary Antioxidants and Related Compounds, 2000). Recently, the Food and Nutrition Board suggested that vitamin E intake among healthy adults is probably higher than the Recommended Dietary Allowance (RDA) but warns that those following a low-fat diet could experience a deficiency (NIH, 2021c).

Vitamin K, a fat-soluble vitamin, is a coenzyme required for blood clotting and bone metabolism. Vitamin K is present in the liver and other body tissues, including the brain, heart, pancreas, and bone. Compared with other fat-soluble vitamins, minimal amounts of vitamin K circulate in the blood due to rapid metabolism and excretion (NIH, 2021d). The clinical status of vitamin K should be regularly evaluated in individuals who take anticoagulants or have bleeding disorders. Infants are injected with vitamin K at birth to decrease the risk of a hemorrhagic event (Hand et al., 2022).

Because fat-soluble vitamins are stored in tissue, higher amounts of these vitamins result in toxicity. In some water-soluble vitamins, high-potency supplementation can also result in adverse health issues (Table 3.1).

B Vitamins

This section outlines water-soluble vitamins, which includes the family of B vitamins and vitamin C. There are eight B vitamins (at times referred to as B complex): thiamine (B₁), riboflavin (B₂), niacin (B₃), pantothenic acid (B₅), pyridoxine (B₆), biotin (B₇), folate (B₉), and cobalamin (B₁₂).

All B vitamins act as coenzymes for catalytic activity and several processes that support every aspect of cellular function, including brain and nervous system functions (Hanna et al., 2022). Although almost all the B vitamins are involved in metabolism, one cannot be substituted for another. Therefore, a specific B vitamin deficiency is associated with a specific disease. In general, deficiency diseases related to B vitamins are rare, partly because of the wide availability of these vitamins in everyday food items, but also because B vitamins that are commonly lost in food processing are added back into the food. For example, when the bran and germ are removed from grains, leaving only the endosperm, B vitamins and vitamin E are also removed (Figure 3.3). Food manufacturers add back the vitamins during food processing. This process is called food enrichment and is subject to government oversight by the U.S. Food and Drug Administration (FDA) (Institute of Medicine [U.S.] Committee on Use of Dietary Reference Intakes in Nutrition Labeling [IOM], 2003; Newman et al., 2020).

Figure 3.3 Food processing strips the whole grain of bran and germ and results in a refined grain. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

Table 3.2 illustrates the function of B vitamins as coenzymes, assisting in metabolizing carbohydrates, fat, and proteins, thus producing energy for body cells via the citric acid cycle. The citric acid cycle occurs in the cell mitochondria, also known as the cell’s powerhouse—this is where the final breakdown for carbohydrates, amino acids, and fatty acids occurs.

B vitamins must have macronutrients (carbohydrates, fat, and protein) available for energy production. Taking a vitamin supplement instead of a balanced meal does not provide a substrate for coenzyme action. Instead, obtaining vitamins through foods is preferred. Remember that none of the other B vitamins can cover a deficiency of another.

Choline, Biotin, and Folate

Other water-soluble substances that are less known include choline, biotin, and folate. Choline is an essential nutrient, not classified as a vitamin or a mineral, and is naturally present in food. Choline is often grouped with the B vitamins because it has similar functions. Vitamin research continues to improve classification, and in 2022 for the first time, a set amount, or Daily Value, for choline intake was included in the Daily Values (DVs), the list of all vitamins and minerals needed (FDA, 2022a). This nutrient is a source of methyl groups needed for many steps in lipid metabolism and is required to generate the neurotransmitter acetylcholine. Although the body produces some choline endogenously in the liver, the amount is sometimes insufficient; additional choline must be ingested through food sources. Most people in the U.S. consume less than the recommended choline intake, yet a deficiency in healthy, nonpregnant individuals is rare, possibly because of the contribution of self-synthesized choline (NIH, 2022b).

Biotin is a water-soluble vitamin that works as a cofactor that catalyzes the metabolism of fatty acids, glucose, and amino acids. Biotin is found in many animal and plant foods. There has never been a reported case of biotin deficiency in a healthy individual consuming a Western diet (NIH, 2022a).

Folate (B₉) functions as a coenzyme in synthesizing ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Folate is also critical in the metabolism of amino acids required for normal cell division. A lack of folate will result in large red blood cells, which is associated with megaloblastic anemia—a condition in which the bone marrow produces unusually large, structurally abnormal, immature red blood cells (NIH, 2022c). Large doses of folate can result in kidney damage.

The chemical structure of folate differs from the more commonly known folic acid. Folates are naturally found in foods, although folic acid is the fully oxidized form of the vitamin used in fortified foods and most dietary supplements. Since 1998, the FDA has mandated that food manufacturers add folic acid to “enriched breads, cereals, flours, corn meals, pasta, rice, and other grain products to reduce the risk of neural tube defects (NTDs)” (NIH, 2022c). NTDs result from a developmental error in the closure of the neural tube early in pregnancy and are one of the most common congenital disabilities in North America (National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 2023). The fortification program is estimated to have increased mean folic acid intakes in the U.S. by about 200 mcg/day, a substantial increase. An unintentional consequence of folate fortification is that people consuming the folate-fortified foods receive extra folate, not just women of childbearing age. However, in the older adult, the consumption of folic acid from fortified foods increases the risk of masking megaloblastic anemia caused by a vitamin B₁₂ deficiency (van Gool et al., 2020).

Vitamin C (Ascorbic Acid)

Vitamin C or ascorbic acid, a water-soluble vitamin, is best known for its coenzyme and antioxidant properties (Abiri & Vafa, 2021). Vitamin C protects cells from premature aging caused by free radicals. Vitamin C stabilizes the cell by accepting or donating an electron. The body is constantly moving electrons around, so vitamin C is used in almost every tissue in the body. Free radicals are the leading cause of disease and inflammation, so vitamin C’s ability to neutralize those free radicals (acting as an antioxidant) is central to lowering heart disease and cancer risk.

Vitamin C also promotes collagen synthesis. Although collagen synthesis is required for maintaining normal vascular function, it also provides metabolic substrates for new blood vessel development (angiogenesis), enhancing blood supply, and bringing more oxygen to the tissues. Vitamin C is necessary for a healthy immune system and increases the absorption of non-heme iron.

The body tightly monitors the plasma concentration of vitamin C. Approximately 70–90% of vitamin C is absorbed in moderate intakes of 30–180 mg/day. Absorption becomes less efficient at doses above 1000 mg/day, with about 50% of the excess excreted in the urine (NIH, 2021b). Most healthy, non-smoking Americans consume enough vitamin C-rich foods to meet the daily requirements of 90 mg/day for males and 75 mg/day for females. According to national nutrition studies, the average vitamin C intake is about 95 mg/day without vitamin supplementation. See Table 3.3 for common fruits and vegetables containing vitamin C.

Large doses of vitamin C can have an adverse effect in people with a family history of kidney or gallstones. Supplementing vitamin C at a level three times or more of the RDA (approximately 3000 mg) can double the amount of oxalate filtering through the kidney and greatly increases the chance of stone formation.

Most water-soluble vitamins are absorbed in the small intestine through the process of diffusion. Riboflavin, however, requires the assistance of a carrier molecule for it to enter the bloodstream. Many water-soluble vitamins function as coenzymes in other cellular reactions and may require additional chemical action before tissues use them. Differences in ease of absorption or food bioavailability, dosage, and chemical form of the vitamin all influence the amount of the vitamin absorbed in the small intestine (Ofoedu et al., 2021).

Certain populations or disease states require vitamin supplementation. In most cases, this is due to an increased need related to disease, aging, pregnancy, and breastfeeding. Table 3.4 displays the water- and fat-soluble vitamins and gives situations where vitamin supplementation may need to occur.