8.2: Water-Soluble Vitamins

There are nine essential water-soluble vitamins - eight B vitamins and vitamin C. These water-soluble vitamins all share similar biological features (Table 8.2). As with the fat-soluble vitamins, the water-soluble vitamins are micronutrients and are required in small amounts daily for optimal health. They tend to be bound to proteins in food and have to be cleaved (separated) in order to be absorbed and available for use by the body. Absorption primarily occurs in the small intestine, though some can occur in the stomach as well (to a lesser extent). Once absorbed, the water-soluble vitamins are circulated directly to the liver in the blood. The body does not store these vitamins, therefore, they are typically not toxic when consumed in large amounts — the body excretes what it does not need. The bioavailability of the water-soluble vitamins can be impacted by nutritional status, meaning that the body will increase absorption of a vitamin if intake has been low, or alternatively, decrease absorption of a vitamin if intake has been high. Furthermore, bioavailability can be impacted by other nutrients and substances in foods, medications, age, and illness status.

Table 8.2 Characteristics of the Water-Soluble Vitamins

Similar properties
Dissolve in H2O Tend to be bound to proteins in food Absorbed primarily in the small intestine, some in stomach (to lesser extent) Circulated directly to the liver Bioavailability can be influenced No toxicity
Functions are diverse
Coenzymes in energy metabolism pathways Carriers of methyl units Free radical damage

The water-soluble vitamins have a diverse range of functions. Most are involved in energy metabolism pathways in some way, often acting as coenzymes. Others are important carriers of methyl units, while others are important in acting as antioxidants to protect the body from free radical damage.

Vitamin B1 —Thiamin

Thiamin is a water-soluble vitamin that needs to be activated to be used by the body. This is done through phosphorylation, whereby two phosphate groups are added to thiamin to form thiamin pyrophosphate (TPP).

Important Roles

Active TPP is a crucial coenzyme that plays an important role in various metabolic pathways, primarily in carbohydrate metabolism. TPP is essential for the reactions that convert glucose into energy, acting as a cofactor for several enzymes involved in this process. TPP is also involved in metabolism of some amino acids used for energy production, as well as the synthesis of neurotransmitters in the nervous system. Overall, by facilitating the breakdown of carbohydrates and amino acids and their entry into energy-producing pathways, TPP is critical for generating cellular energy in the form of ATP.

Dietary Sources

The RDA for thiamin is 1.1 mg/day for women and 1.2 mg/day for men. Thiamin is found abundantly in foods such as whole grains, pork, legumes, seeds, and fortified cereals (Figure 8.10).

Figure 8.10 Foods such as black eyed peas are rich sources of vitamin B1 (thiamin). Image by Jud McCranie is licensed under CC BY-SA 4.0.

In terms of bioavailability, absorption of thiamin will increase when intake is chronically low, and decrease when intake is chronically high. There are antithiamin factors in some food sources that can interfere with the bioavailability of thiamin, interfering with the absorption, utilization, or activation of thiamin. Anti-thiamin factors can include enzymes that break thiamin down directly or chemical compounds such as polyphenols that can inhibit thiamin’s activity. Foods such as raw fish, tea, berries, and certain vegetables like cabbage or Brussels sprouts, often contain anti-thiamin factors. Consuming foods with these anti-thiamin factors could lead to thiamin deficiency.

Consequences of Deficiency

Vitamin B1 deficiency often presents initially with symptoms such as headache, fatigue, nausea, and abdominal discomfort. However, it can lead to beriberi, which presents in two main types, with distinct symptoms and affecting different physiological systems.

• Dry beriberi typically results from chronic low thiamin intake, especially in adults with poor diets or malabsorption disorders. It impacts the nervous system, leading to nerve damage, muscle weakness, difficulty walking, numbness or tingling in the hands and feet, and eventual loss of coordination and reflexes.
• Wet beriberi tends to occur more rapidly and is often seen in areas where high carbohydrate, low thiamin diets are common (such as in areas where there is consumption of polished or milled rice as a primary staple food). Wet beriberi impacts the cardiovascular system, leading to swelling (edema) in the legs, rapid heartbeat, enlargement of the heart, difficulty breathing, and congestive heart failure. This form can be life threatening if not treated promptly.
• Wernicke-Korsakoff Syndrome (sometimes referred to as cerebral beriberi) is typically associated with alcoholism. An acute phase known as Wernicke’s encephalopathy occurs with confusion, poor coordination, and eye movement abnormalities. This may be followed by a chronic condition known as Korsakoff’s psychosis with short-term memory loss and confusion. This is most commonly seen in situations of chronic alcoholism, where both intake and absorption of thiamin are impaired.

Vitamin B2 —Riboflavin

Riboflavin is a multi-ring structure attached to a ribose (5-carbon sugar, lending to its name). It is a vital water-soluble vitamin that plays a crucial role in various bodily functions such as energy production, cellular growth, and the metabolism of fats, drugs, and steroids.

Important Roles

Riboflavin is a precursor to the coenzymes flavin adenine dinucleotide (FAD) and flavin mono nucleotide (FMN), which are important for cellular respiration and energy metabolism, resulting in the formation of ATP. Riboflavin is also involved in the metabolism of other vitamins: it aids in converting vitamin A and folate to their active forms, converting tryptophan to niacin, and forming vitamin B6 and vitamin K. It also aids in the function of cytochrome P-450, a family of enzymes that metabolize drugs and toxins.

Dietary Sources

The RDA for riboflavin is 1.1 mg/day for women and 1.3 mg/day for men. It is abundant in meat and dairy products, found in sources such as milk, yogurt, eggs, beef liver, mushrooms, almonds, and fortified cereals (Figure 8.11). When intake of riboflavin is chronically low, the body will increase active transport mechanisms for absorption; conversely, when intake is chronically high, simple diffusion is used for absorption.

Figure 8.11 Yogurt, eggs, and mushrooms are good examples of food sources of vitamin B2 (riboflavin). Photo by Andres Felipe Rengifo on Pexels.

The bioavailability of riboflavin can be significantly decreased by exposure to light. Fun fact: this is why milk is packaged in opaque or cardboard containers!

Consequences of Deficiency

Riboflavin deficiencies are typically associated with broader nutrient deficiencies and overall malnutrition. Riboflavin deficiency may result in ariboflavinosis with symptoms such as cheilosis (swelling and fissuring of the lips), glossitis (swollen and inflamed tongue), and stomatitis (swollen, inflamed, sore mouth). Muscle weakness and confusion can also be seen with ariboflavinosis.

Vitamin B3 —Niacin

Niacin is found in various foods in two primary forms —nicotinic acid and nicotinamide. Additionally, the body can convert the essential amino acid tryptophan into niacin (nicotinamide). This conversion requires riboflavin (vitamin B2) due to the need for the coenzyme FAD.

Important Roles

Niacin is another essential water-soluble vitamin important in supporting energy metabolism. It is a key component of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which extract energy from carbohydrates, fatty acids, and proteins during cellular respiration. Niacin is also often used as a dietary supplement to help manage cholesterol levels, as it has been shown to increase levels of high-density lipoprotein cholesterol and lower triglyceride levels.

Dietary Sources

The RDA for niacin is 14 mg/day for women and 16 mg/day for men. The tolerable upper limit is established at 35 mg/day with concern that chronic large doses of nicotinic acid can increase plasma glucose levels and damage the liver (primarily from high dose supplementation). Niacin is found in both plant- and animal-based foods, with animal sources providing higher bioavailability. It is also synthesized from tryptophan, which is abundant in animal proteins. Niacin can be found in food sources such as poultry, beef, fish, tomatoes, mushrooms, and fortified cereals (Figure 8.12). Niacin is measured in terms of a Niacin Equivalent (NE), which refers to the combined amounts of niacin and tryptophan in foods.

Figure 8.12 Citrus foods and avocados are good examples of sources of vitamin B3 (niacin). Modified from photo by Bernadette Wurzinger courtesy of and copyright Free Range Stock.

Consequences of Deficiency

Niacin deficiency is typically seen in conjunction with general malnutrition or chronic alcoholism. Deficiency causes pellagra, which is characterized by the “3 D” symptoms — dermatitis, dementia, and diarrhea. The skin irritation experienced with pellagra is typically made worse by sunlight. Niacin deficiency can also be caused by a condition called Hartnup disorder. This is a genetic abnormality that impairs the absorption of tryptophan, thereby removing a source of niacin.

Vitamin B5 — Pantothenic Acid

Pantothenic acid is a nitrogen-containing compound, a combination of pantoic acid and beta-alanine. Interestingly, its name comes from the Greek pantothen, meaning “from everywhere,” because it is in almost all foods at least in small amounts.

Important Roles

Pantothenic acid is involved in the synthesis of coenzyme A (CoA), a molecule essential for the breakdown of macronutrients and production of energy. CoA is also crucial for fatty acid synthesis and breakdown and synthesis of cholesterol and bile acids.

Dietary Sources

The adequate intake level of pantothenic acid has been established to be 5 mg/day for both men and women. It is found in almost every plant and animal food consumed in the diet (Figure 8.13), and is abundant in fortified cereal as well.

Figure 8.13 Examples of food sources of vitamin B5 (pantothenic acid). Image from pxhere is in the CC0 1.0 Public Domain.

Consequences of Deficiency

Pantothenic acid deficiency is extremely rare, especially in developed countries, because it is so widely available in food. However, severe deficiency can result in numbness and burning sensations in the hands and feet, fatigue, headache, weakness, nausea, and vomiting.

Vitamin B6 —Pyridoxine

The term vitamin B6 refers to six common forms, namely pyridoxal, pyridoxine, pyridoxamine, and their phosphorylated forms. All forms are made of a modified nitrogen-containing ring structure and have similar biological activity.

Important Roles

Vitamin B6 is converted to pyridoxal phosphate (PLP), the active form of vitamin B6 in the body. PLP acts as a coenzyme in more than 100 chemical reactions. It is important in the metabolism of proteins and amino acids, and helps to prepare amino acids to enter the citric acid cycle. Significantly, vitamin B6 is necessary for making nonessential amino acids. This means that without vitamin B6, all 20 amino acids would be essential!

Dietary Sources

The RDA for vitamin B6 is established to be 1.3 mg/ day for both men and women. Vitamin B6 is found in dietary sources including chickpeas, tuna, salmon, bananas, sweet potatoes, and fortified cereal (Figure 8.14). Vitamin B6 is fairly unstable, so is not added to enriched foods.

Figure 8.14 Tuna and chickpeas are great examples of food sources of vitamin B6 (pyroxidine). Modified from Image by Alesia Kozic from Pexels

Consequences of Deficiency

Symptoms of a vitamin B6 deficiency are similar to those of a riboflavin deficiency, including cheilosis, glossitis, stomatitis, and fatigue. One of the differentiators is the presence of microcytic hypochromic anemia, where red blood cells are small and pale. This results in inadequate heme production, so there are lower concentrations of hemoglobin in the red blood cells. Overall, the anemia interferes with the ability of the red blood cells to deliver oxygen to tissues.

Though there are typically no concerns about toxicity with water-soluble vitamins, vitamin B6 can be toxic if it is supplemented excessively. This can result in severe neurological problems, including difficulty walking and numbness in the feet and hands. For this reason, the tolerable upper limit has been established as 100 mg/day.

Vitamin B7 —Biotin

Biotin, like many of the other water-soluble vitamins, supports the metabolism of carbohydrates, fats, and proteins. It is typically attached to the proteins in food and is cleaved by small intestine enzymes to release the free biotin form for absorption.

Important Roles

Biotin is necessary for the formation of glucose and fatty acids, which are used as fuel by the body. It plays a role in gene expression and cell growth, supporting the health of hair, nails, and skin.

Dietary Sources

The adequate intake level of biotin is established as 30 µg/day for both men and women. It is found abundantly in foods such as eggs, nuts, seeds, salmon, sweet potatoes, and avocados (Figure 8.15). Biotin is also produced by the bacteria in the large intestine, though this is not a significant source.

Figure 8.15 Sweet potatoes are one of many rich sources of vitamin B7 (biotin). Modified from Image by Jess Loiterton from Pexels.

The bioavailability of biotin is decreased with chronic alcohol consumption. It is also reduced when biotin is consumed with foods containing the protein avidin. Avidin attaches to biotin and makes the vitamin difficult to absorb.

Consequences of Deficiency

Biotin deficiency is rare, though can occur particularly in people who consume raw egg whites. This is because egg whites contain avidin, which binds biotin and makes it unavailable (cooking eggs denatures avidin so biotin can be released and absorbed!). Deficiency of biotin may cause thinning hair, rash around the eyes, nose, and mouth, and lethargy and fatigue.

Vitamin B9 — Folate

Folate, also known as vitamin B9, exists in several forms. Folate is naturally occurring and found in foods and the body. Folic acid is the most oxidized and stable form, used in supplements and fortified foods. The most active form, 5- methylfolate (5-MTHF), is readily used by the body.

Important Roles

Folate is required for the normal growth and development of nerve tissue in the fetus, therefore making maternal intake of folate crucial. It is believed this may have to do with the folate-containing enzymes needed for DNA synthesis. Folate is required for the closure of the neural tube, the tissue that becomes the brain and spinal cord during development.

Dietary Sources

Dietary folate equivalents (DFE) is a measurement that estimates the amount of folate absorbed by the body since absorption is variable. Specifically, bioavailability varies depending on the form of folate in food, where folic acid is more readily absorbed than the folate naturally occurring in food.

The RDA for folate is 400 µg/day DFE for both men and women. However, the RDA increases to 600 µg/day for pregnant women or those capable of becoming pregnant. The tolerable upper limit is set at 1000 µg/day, though there is no evidence for toxicity. Folate is commonly found in food sources such as leafy green vegetables, legumes, beans, oranges, and fortified cereals or grains (Figure 8.16).

Figure 8.16 Cereals and grains are great sources of vitamin B9 (folate). Photo by Ovidiu Creanga on Pexels.

Consequences of Deficiency

Folate is exceptionally important during pregnancy, and a maternal deficiency during pregnancy increases the risk of neural tube defects (NTDs) in the fetus.

NTDs are a group of birth defects that affect the brain and spinal cord, occurring when the neural tube doesn’t close completely. Spina bifida is the most common type of NTD (Figure 8.17), typically involving the protrusion of the spinal cord and fluid and resulting in a range of disabilities. This can result in conditions such as mental impairment, partial paralysis, or poor bowel and bladder control. Folic acid supplementation before and during early pregnancy can significantly reduce the risk of NTDs. Furthermore, folic acid has been added to foods labeled as enriched, such as breads, pastas, rice, and cereals. This initiative has led to a decrease in the number of babies born with NTDs each year.

Figure 8.17 Spina bifida is the most common type of neural tube defect. Image from the Centers for Disease Control and Prevention is licensed under Creative Commons CC0 1.0 Universal Public Domain Dedication.

Outside of pregnancy, folate deficiency (in a mild form) can lead to fatigue, weakness, and headaches. In a more severe deficiency, megaloblastic microcytic anemia can occur where red blood cells remain immature as megaloblasts. Megaloblasts are large and have organelles not normally found in red blood cells. As with any anemia, this impacts the oxygen-carrying capacity of the cells.

Vitamin B12 —Cobalamin

Cobalamin is a structure that contains the trace element cobalt and nitrogen atoms. It can only be made by microorganisms, meaning that the presence of cobalamin in food is the result of it being made in the microorganisms living in the food source’s environment or GI tract. Cobalamin is bound to proteins in food, and these are removed in the stomach by acids and the protease pepsin.

The free form of cobalamin is bound to R protein and intrinsic factor (both made in the stomach). R protein is released in the small intestine, and the vitamin B12-intrinsic factor complex is absorbed in the small intestine. After absorption, vitamin B12 is released from intrinsic factor and bound to transcobalamin for transport through the blood.

Important Roles

Vitamin B12 is vital for red blood cell formation and DNA synthesis. Vitamin B12 acts as a cofactor for enzymes involved in DNA synthesis, which is essential for cell division and maturation. Red blood cells are constantly being produced and replaced, and vitamin B12 is essential for this. Vitamin B12 also allows the body to use amino acids and fatty acids for ATP production, and is a coenzyme in the conversion of homocysteine to methionine.

During the conversion of homocysteine to methionine, the inactive form of folate (5-methyltetrahydrofolate) is converted to its active form of tetrahydrofolate (THF) through the transfer of a methyl group to vitamin B12. The methylated vitamin B12 then transfers a methyl group to homocysteine to form methionine. Without adequate vitamin B12, homocysteine levels build up in the blood and traps folate in its inactive form (in this way, vitamin B12 deficiency can lead to secondary folate deficiency).

Dietary Sources

The RDA for cobalamin is 2.4 µg/day for both men and women. Cobalamin is primarily found in animal-based foods. Excellent sources include shellfish, beef, liver, tuna, salmon, eggs, and dairy products like milk, yogurt and cheese (Figure 8.18).

Figure 8.18 Examples of food sources of vitamin B12 (cobalamin). Image by Marco Verch from CCNull is licensed under CC BY 2.0 DE Attribution 2.0 Germany.

Many breakfast cereals are also fortified with vitamin B12. This is especially important for vegans who typically need fortified foods or supplements.

Consequences of Deficiency

Cobalamin deficiency is typically due to inadequate dietary intake or poor absorption. Megaloblastic macrocytic anemia can result, in addition to neurological issues like numbness, tingling, memory loss, difficulty sleeping, and balance issues.

Pernicious anemia is an autoimmune disease where antibodies destroy the parietal cells in the stomach that produce intrinsic factor. Intrinsic factor is required for the absorption of vitamin B12. Pernicious anemia can occur even when large amounts of vitamin B12 are consumed, and is treated with injections instead of orally.

Ascorbic Acid —Vitamin C

Vitamin C is a water-soluble vitamin made from glucose by all plants and most animals, but not humans. Absorption of vitamin C occurs via the use of glucose transport proteins in the small intestine. If there is chronically high intake of vitamin C, it will also be absorbed in the stomach to a lesser extent.

Important Roles

Vitamin C plays a vital role in many functions of the body. It acts as a powerful antioxidant, protecting cells from damage by free radicals. Exposure to smog, cigarette smoke, ozone, or intense sunlight can increase free radical production. Vitamin C, acting as an antioxidant system, is able to help stabilize free radicals before they oxidize other compounds and repair damage they cause. Vitamin C can easily accept and donate electrons, so is involved in a variety of redox reactions. It is also essential for the synthesis of collagen, a protein that helps maintain the structure of the skin, blood vessels, bones, and connective tissues. Specifically, the formation of collagen requires a copper-containing enzyme to be oxidized. Vitamin C is needed to reduce the copper-containing enzyme between reactions so it can continue to form collagen.

Minerals such as iron and copper are better absorbed in their reduced states. Vitamin C can chemically reduce them in the GI tract. For example, vitamin C in orange juice reduces cereal’s ferric iron to ferrous iron, making it readily bioavailable. This means that drinking orange juice, for example, along with iron-fortified cereal increases the amount of iron absorbed from the cereal.

Dietary Sources

The RDA for vitamin C is 75 mg/day for women and 90 mg/day for men. Vitamin C is found primarily in fruits and vegetables, particularly in citrus fruits (such as oranges, grapefruits, lemons), strawberries, kiwi, bell peppers, broccoli, and tomatoes (Figure 8.19).

Figure 8.19 Citrus foods are rich sources of vitamin C (ascorbic acid). Image by PublicDomainPictures from Pixabay.

Consequences of Deficiency

Vitamin C deficiency is rare, though can still be seen in developing countries, children, elderly on restricted diets, and alcoholics. A deficiency in vitamin C can lead to scurvy, a condition marked by fatigue, bleeding gums, joint pressure, and poor wound healing, all symptoms due to impaired collagen production.

Health Note

B vitamins help convert food into energy and support brain function. Vitamin C boosts immune function and helps the body make collagen.

Fun Fact

B12 is only naturally found in animal products — vegans need to supplement!

Sailors used to eat citrus fruits (with vitamin C) to prevent scurvy on long voyages!