Biol 125: Exhaustive Guide to Water-Soluble Vitamins

Introduction to Vitamins and Micronutrients

Vitamins are defined as organic compounds required in the diet in small amounts to regulate body functions. As essential nutrients, they generally cannot be synthesized by the body in adequate amounts (or at all) and must be obtained through dietary intake. The primary exception to this is Vitamin D, which functions more like a hormone and can be synthesized from cholesterol following exposure to ultraviolet sunlight.

To be officially classified as a vitamin, the lack of the compound must result in specific deficiency symptoms that are alleviated once the compound is reintroduced to the diet. Currently, there are 13 known vitamins in human nutrition. While Choline is an essential water-soluble nutrient with dietary recommendations, it is not classified as a vitamin at this time.

Vitamins vs. Macronutrients

Vitamins differ significantly from macronutrients (carbohydrates, fats, and proteins) in terms of structure and function:

• Quantity: Vitamins are required in tiny (micronutrient) amounts.

• Energy: Vitamins are not broken down to yield energy ($0\,kcal/g$).

• Structure: They are not assembled into body structures (unlike proteins or minerals).

• Regulatory Role: Many vitamins act as catalysts for chemical reactions. For instance, B-vitamins function as coenzymes, which are organic non-protein molecules that bind to and activate enzymes.

• Specific Functions: Some vitamins serve as antioxidants or as hormones.

Classification of Vitamins

Vitamins are grouped based on their solubility, which dictates their absorption, transport, storage, and excretion.

Water-Soluble Vitamins

This group includes Vitamin C (Ascorbic Acid) and the eight B-v-itamins (Thiamin, Riboflavin, Niacin, Pyridoxine, Biotin, Pantothenic Acid, Folate, and B12).

• Excretion: Excess amounts are generally excreted by the kidneys, meaning they must be consumed regularly.

• Storage: Most are not stored in the body, with the notable exception of Vitamin B12.

• Toxicity: Although excreted, toxicity is possible through high-dose supplementation, particularly with Niacin and Vitamin B6.

Fat-Soluble Vitamins

This group includes Vitamins A, D, E, and K.

• Solubility: They are found in foods containing fats and oils.

• Absorption: They require dietary fat for absorption, involving emulsification into micelles and incorporation into chylomicrons.

• Storage: They are stored in the liver and adipose (fat) tissue, which means it takes longer (at least a few days) for deficiency symptoms to manifest.

• Risks: Deficiencies can occur in individuals with very low fat intake or fat malabsorption issues.

Vitamin Enrichment and Fortification

Processing and cooking can strip vitamins from food. To mitigate this, manufacturers use enrichment and fortification.

Enrichment

Enrichment is the process of replacing nutrients that were lost during food processing. A primary example is the refinement of grains. During refinement, the following are removed and later replaced with synthetic versions in "enriched white bread" or flour:

• Thiamin

• Riboflavin

• Niacin

• Folic Acid (specifically added to enriched white flours)

• Iron (a mineral, also added back to white flour)

Fortification

Fortification is the addition of nutrients to a food that were not originally present or were present in insignificant amounts.

• Example 1: Vitamin D is added to milk.

• Example 2: Iodide (a mineral) is added to salt.

• Example 3: Folic acid added to grains is technically a form of fortification now required by law.

Dietary Reference Intakes (DRIs) for Vitamins

Requirements for healthy individuals in the U.S. and Canada are based on the DRIs:

• Recommended Dietary Allowance (RDA): The average daily level of intake sufficient to meet the nutrient requirements of nearly all ($97\%$\text{--}$98\%$) healthy individuals.

• Adequate Intake (AI): An estimation used when there is insufficient data to establish an RDA.

• Tolerable Upper Intake Level (UL): The maximum daily intake unlikely to cause adverse health effects; used because high doses of certain vitamins are toxic.

• Limitations: RDAs are primarily established to prevent deficiency diseases; however, individual needs may be higher for optimal function across multiple body systems.

Thiamin (Vitamin B1)

Thiamin was the first compound recognized as a vitamin. It is easily destroyed by high cooking temperatures.

Metabolism and Functions

• Absorption: Occurs in the duodenum of the small intestine.

• Active Form: It is phosphorylated intracellularly into thiamin pyrophosphate (TPP), which contains two phosphates.

• Core Function: TPP acts as a coenzyme in reactions that remove a carbon. It is essential for transforming pyruvate into acetyl-CoA (the bridge between glycolysis and the Citric Acid Cycle).

• Energy Production: Necessary for producing ATP from glucose.

• Nervous System: Required for the production of the neurotransmitter acetylcholine.

Requirements and Sources

• RDA: $1.2\,mg/day$ for men; $1.1\,mg/day$ for women. Requirements increase with high calorie/sugar intake, pregnancy, and lactation.

• Sources: Brewer's yeast, wheat germ, whole grains, beans, seeds, and pork. Refined grains are sprayed with synthetic thiamin.

• Antagonists: Thiaminases (found in raw shellfish and raw fish) can destroy thiamin but are inactivated by cooking. Other anti-thiamin factors exist in tea, coffee, betel nuts, blueberries, and red cabbage. Alcohol also depletes thiamin.

Deficiency: Beri-Beri

Beri-beri (meaning "I can't, I can't") was historically prevalent in populations relying on polished white rice, as thiamin is located in the bran and germ of the grain.

• Early Symptoms: Depression and weakness (after approximately 10 days on a thiamin-free diet).

• Dry Beri-Beri (Neuritic): Characterized by nervous system degeneration, tingling in extremities, confusion, irritability, and poor coordination.

• Wet Beri-Beri (Cardiovascular): Characterized by an enlarged heart, edema, and heart failure.

• Wernicke-Korsakoff Syndrome: Associated with chronic heavy alcohol consumption. Symptoms include nystagmus (involuntary eye movement), staggering, mental confusion, and psychosis.

Riboflavin (Vitamin B2)

Riboflavin is a fluorescent yellow-green compound that is stable to heat and acid but highly sensitive to light.

Metabolism and Functions

• Active Forms: It forms two coenzymes: Flavin Adenine Dinucleotide (FAD) and Flavin Mononucleotide (FMN).

• Energy Metabolism: FAD and FMN accept and release electrons in the Citric Acid (Kreb's) Cycle and the Electron Transport Chain to form ATP.

• Beta-Oxidation: FAD is required to break down fatty acids into acetyl-CoA.

• Activation: Riboflavin is necessary to convert other vitamins (folate, niacin, B6, and Vitamin K) into their active forms.

Requirements and Sources

• RDA: $1.3\,mg/day$ for men; $1.1\,mg/day$ for women.

• Sources: Dairy products, liver, meat, fish, poultry, green vegetables, almonds, and enriched grains.

• Protection: Because it is destroyed by light, milk is typically sold in opaque or cardboard containers.

Deficiency: Ariboflavinosis

Deficiency is uncommon but can occur after $2\,months$ on a riboflavin-free diet. Because riboflavin exists alongside other B-vitamins in food, isolated deficiency is rare.

• Symptoms: Cheilosis (cracks at the corners of the mouth), glossitis (inflammation of the tongue), itchy eyes, hypersensitivity to light, seborrheic dermatitis (greasy, scaly skin), and confusion.

Niacin (Vitamin B3)

Niacin exists in two forms: nicotinic acid and nicotinamide, both of which convert to the coenzymes NAD and NADP. It is very stable to light, heat, acid, and oxidation.

Metabolism and Functions

• Synthesis: Niacin can be synthesized in the body from the amino acid tryptophan. $60\,mg$ of tryptophan yields $1\,mg$ of niacin (defined as $1\,NE$, or Niacin Equivalent).

• Energy Pathways: Participates in glycolysis, the Citric Acid Cycle, and the Electron Transport Chain (via NAD).

• Anaerobic Metabolism: NAD is required for the formation of lactic acid from pyruvate.

• Synthesis: NADP is involved in fatty acid and cholesterol synthesis.

• Other Roles: Essential for alcohol metabolism and the health of the skin, nervous system, and digestive system.

Requirements and Sources

• RDA: $16\,mg/day$ for men; $14\,mg/day$ for women.

• Sources: Meat, fish, poultry, legumes, mushrooms, dairy, wheat bran, and enriched grains.

• Bioavailability: Corn contains niacin bound to other molecules that make it unavailable. In Mexico and South America, corn is traditionally treated with lime water (calcium hydroxide), which releases the niacin and makes it bioavailable.

Deficiency: Pellagra

Pellagra was historically common among the poor who relied on untreated corn. It was once thought to be infectious but is a nutritional deficiency.

• The 4 Ds: Dermatitis (resembling sunburn, worsened by sun), Diarrhea, Dementia (preceded by irritability and confusion), and eventually Death.

Toxicity

• Symptoms: Flushing of the skin, tingling, red rash, nausea, vomiting, and impaired liver function.

• UL: $35\,mg/day$ (set to prevent skin flushing produced by supplements).

Biotin (Vitamin B7)

Biotin acts as a cofactor in major metabolic pathways involving the addition of carboxyl groups.

Metabolism and Functions

• Cleavage: In foods, biotin is bound to protein and must be broken down by the enzyme biotinidase for absorption.

• Active Roles:

  • Carbohydrate Metabolism: Adds $COOH$ to 3-carbon pyruvate to yield 4-carbon oxaloacetate.

  • Gluconeogenesis: Synthesizes glucose from non-carbohydrate sources (e.g., amino acids).

  • Fatty Acids: Synthesis of fatty acids from acetyl-CoA and metabolism of odd-chain fatty acids.

• Additional Source: Microorganisms in the colon can synthesize some biotin, which can be absorbed.

Requirements and Deficiency

• AI: $30\,μg/day$.

• Antagonist: Avidin, a protein in raw egg whites, binds biotin and prevents absorption. Deficiency can occur with prolonged raw egg white consumption or biotinidase deficiency.

• Symptoms: Scaly red rash around the eyes, nose, and mouth, loss of appetite, nausea, depression, fatigue, hair loss, and hallucinations.

Pantothenic Acid

Derived from the Greek word pantos (meaning "from everywhere"), this vitamin is widespread in the food supply.

Metabolism and Functions

• Active Form: It is a major component of Coenzyme A (CoA).

• Metabolism: CoA is part of acetyl-CoA, which is central to the metabolism of all macronutrients.

• ATP Synthesis: Involved in the Citric Acid Cycle and essential for activating fatty acids for beta-oxidation.

Requirements and Deficiency

• AI: $5\,mg/day$.

• Deficiency: Rare. Observed in WWII prisoners of war. Symptoms include "burning feet" (numbness/tingling), nausea, insomnia, and fatigue.

Vitamin B6

B6 refers to a family of three compounds: pyridoxine, pyridoxal, and pyridoxamine.

Metabolism and Functions

• Active Form: Pyridoxal Phosphate (PLP).

• Protein Metabolism: PLP is involved in more than 100 enzymes, specifically:

  • Deamination: Removing amino groups for urea disposal.

  • Transamination: Transferring amino groups to synthesize nonessential amino acids.

• Specific Syntheses:

  • Conversion of tryptophan to niacin.

  • Conversion of methionine to cysteine (helps maintain normal levels of homocysteine, which is toxic to arteries).

  • Synthesis of neurotransmitters (serotonin, dopamine, GABA, norepinephrine).

  • Synthesis of hemoglobin, antibodies, and myelin lipids.

Requirements and Toxicity

• Sources: Animal protein (meat, fish, poultry), whole wheat, brown rice, seeds, and bananas. Note: B6 is not replaced in enriched grains.

• Antagonists: Excessive alcohol, oral contraceptives, and certain drugs.

• Toxicity: Over $500\,mg/day$ chronically or $2\text{--}6\,g/day$ short-term can cause irreversible nerve damage.

• UL: $100\,mg/day$.

Deficiency

• Symptoms include microcytic anemia, depression, peripheral nerve degeneration, and decreased antibody formation.

Folate and Vitamin B12 Relationship

These two vitamins have overlapping roles in DNA synthesis and the conversion of homocysteine to methionine. A deficiency in either leads to megaloblastic anemia.

Folate (Folic Acid/B9)

• Forms: Food folate is a polyglutamate; the supplement form is a monoglutamate called folic acid.

• Absorption: Enzymes in the small intestine remove glutamates to allow absorption. The active coenzyme form is THF (tetrahydrofolic acid), formed with the help of Vitamin C.

• Functions: DNA synthesis, cell division (crucial for bone marrow and GI tract), and neural tube closure in the first month of pregnancy.

• RDA: $400\,μg/day\,DFE$ (Dietary Folate Equivalents). RDA for pregnancy is $600\,μg/day$.

• DFE Conversions:

  • $1\,DFE = 1\,μg$ food folate.

  • $1\,DFE = 0.6\,μg$ folic acid from fortified food/supplements with food.

  • $1\,DFE = 0.5\,μg$ supplement on an empty stomach.

• Deficiency: Megaloblastic anemia (large, immature red blood cells), neural tube defects (spina bifida), and increased risk of cardiovascular disease.

• Toxicity: UL is $1000\,μg/day$. High folic acid can mask B12 deficiency.

Vitamin B12 (Cobalamin)

• Structure: Largest, most complex vitamin; contains cobalt.

• Absorption Process:

  1. cleaved from dietary protein by HCL and pepsin in the stomach.

  2. Binds to R-protein in gastric juice.

  3. Released from R-protein by trypsin in the small intestine.

  4. Binds to Intrinsic Factor (IF) produced in the stomach.

  5. The B12/IF complex is absorbed in the ileum.

• Storage: $50\%\text{--}90\%$ is stored in the liver ($5\text{--}12\,mg$). It takes about $4\,years$ of deprivation for deficiency to appear.

• Functions: Activates folate; maintains the myelin sheath; converts homocysteine to methionine.

• Pernicious Anemia: A fatal condition caused by a lack of IF or HCL (often due to atrophic gastritis/autoimmune issues in the elderly). Symptoms include megaloblastic anemia and permanent nerve damage starting in extremities.

• Sources: Found only in animal products. Vegans must supplement.

Vitamin C (Ascorbic Acid)

Historically identified by James Lind in 1747 to cure scurvy in sailors. It is a 6-carbon molecule similar to glucose.

Metabolism and Functions

• Synthesis: Most animals can synthesize it from glucose; humans and primates cannot.

• Antioxidant: Regenerates oxidized Vitamin E, neutralizes free radicals in smoke, and prevents oxidative damage in fluids.

• Coenzyme Roles:

  • Essential for collagen and connective tissue formation.

  • Drug detoxification in the liver.

  • Enhances iron absorption.

  • Reduces conversion of nitrates to carcinogenic nitrosamines.

Requirements and Sources

• RDA: $90\,mg/day$ (men); $75\,mg/day$ (women).

• Prevention Threshold: $10\,mg/day$ prevents scurvy.

• Tissue Saturation: $200\,mg/day$.

• Sources: Citrus, cruciferous vegetables, peppers, papayas, and potatoes.

• Biological Fact: Pigs synthesize approximately $8\,g$ of Vitamin C per day.

Deficiency: Scurvy

Charactersized by collagen deformation. Symptoms include bleeding gums, loose teeth, fragile blood vessels (pinpoint hemorrhages), bone deformity, and slow wound healing.

Toxicity

Non-toxic systemically (excess is not absorbed), but large doses can cause nausea, cramps, and diarrhea due to water being drawn into the intestines. It may cause kidney stones in susceptible individuals.

Each Vitamin Deficiency

Thiamin (Vitamin B1) Deficiency: Beri-Beri

• Early Symptoms: Depression and weakness (after approximately 10 days on a thiamin-free diet).

• Dry Beri-Beri (Neuritic): Characterized by nervous system degeneration, tingling in extremities, confusion, irritability, and poor coordination.

• Wet Beri-Beri (Cardiovascular): Characterized by an enlarged heart, edema, and heart failure.

• Wernicke-Korsakoff Syndrome: Associated with chronic heavy alcohol consumption. Symptoms include nystagmus (involuntary eye movement), staggering, mental confusion, and psychosis.

Riboflavin (Vitamin B2) Deficiency: Ariboflavinosis

• Symptoms: Cheilosis (cracks at the corners of the mouth), glossitis (inflammation of the tongue), itchy eyes, hypersensitivity to light, seborrheic dermatitis (greasy, scaly skin), and confusion.

Niacin (Vitamin B3) Deficiency: Pellagra

• The 4 Ds: Dermatitis (resembling sunburn, worsened by sun), Diarrhea, Dementia (preceded by irritability and confusion), and eventually Death.

Biotin (Vitamin B7) Deficiency

• Symptoms: Scaly red rash around the eyes, nose, and mouth, loss of appetite, nausea, depression, fatigue, hair loss, and hallucinations.

Pantothenic Acid Deficiency

• Symptoms: "Burning feet" (numbness/tingling), nausea, insomnia, and fatigue.

Vitamin B6 Deficiency

• Symptoms: Microcytic anemia, depression, peripheral nerve degeneration, and decreased antibody formation.

Folate (Folic Acid/B9) Deficiency: Megaloblastic Anemia

• Symptoms: Large, immature red blood cells, neural tube defects (spina bifida), and increased risk of cardiovascular disease.

Vitamin B12 Deficiency: Pernicious Anemia

• Symptoms: Megaloblastic anemia and permanent nerve damage starting in extremities, often due to lack of Intrinsic Factor or HCL due to atrophic gastritis/autoimmune issues in the elderly.

Vitamin C (Ascorbic Acid) Deficiency: Scurvy

• Symptoms: Bleeding gums, loose teeth, fragile blood vessels (pinpoint hemorrhages), bone deformity, and slow wound healing.

• Toxicity: Non-toxic systemically, but large doses can cause nausea, cramps, and diarrhea due to water being drawn into the intestines. It may cause kidney stones in susceptible individuals.