Water-soluble Vitamins and their Deficiencies

Water-soluble vitamins are soluble in the blood and minimally stored in the body, unlike fat-soluble vitamins. The most clinically important water-soluble vitamins include vitamin B1 (thiamin), vitamin B2 (riboflavin), vitamin B3 ( niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B7 (biotin), vitamin B9 ( folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12), vitamin B12 ( cobalamin Cobalamin A cobalt-containing coordination compound produced by intestinal microorganisms and found also in soil and water. Higher plants do not concentrate vitamin B 12 from the soil and so are a poor source of the substance as compared with animal tissues. Intrinsic factor is important for the assimilation of vitamin B 12. Folate and Vitamin B12) (the last 2 being some of the most clinically important vitamins and discussed separately), and vitamin C (ascorbic acid). Many of these vitamins are critical components of different metabolic pathways and play important roles in normal cell function. Most are found in our daily diet, but some people with restrictive diets, malabsorptive conditions, or alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder may present clinically with vitamin deficiencies and their consequences. Since they are water-soluble and excreted by the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy, most of these vitamins do not reach toxic levels.

Last updated: Oct 3, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Vitamins are important organic substances that are required for normal metabolic functions These substances cannot be synthesized by the body; they must be ingested in the diet. The vitamins are divided into water-soluble and fat-soluble vitamins. 

  • The most clinically important water-soluble vitamins are the B vitamins and vitamin C. 
  • Deficiencies of these vitamins can lead to clinical manifestations.
  • In some cases, overuse can result in toxicity Toxicity Dosage Calculation, but for most of the water-soluble vitamins, excess is simply excreted by the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy.
  • Intake recommendations are listed as a U.S. Recommended Dietary Allowance (RDA), which is the average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals. 

Summary of clinically important water-soluble vitamin deficiencies

Table: Summary of clinically important water-soluble vitamin deficiencies
Vitamin Clinical condition caused by deficiency
B1 (thiamine)
  • Beriberi:
    • Infantile beriberi
    • Dry beriberi
    • Wet beriberi
  • Wernicke-Korsakoff syndrome Wernicke-Korsakoff syndrome 2 different syndromes that are different stages of the same disease including Wernicke’s encephalopathy and Korsakoff psychosis.Wernicke-Korsakoff syndrome is seen in patients with alcohol use disorder 8–10 times more than in the general population. Wernicke Encephalopathy and Korsakoff Syndrome
B3 ( niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs) Pellagra
Vitamin C Scurvy
Folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12 and vitamin B12
  • Megaloblastic anemia Megaloblastic anemia Megaloblastic anemia is a subset of macrocytic anemias that arises because of impaired nucleic acid synthesis in erythroid precursors. This impairment leads to ineffective RBC production and intramedullary hemolysis that is characterized by large cells with arrested nuclear maturation. The most common causes are vitamin B12 and folic acid deficiencies. Megaloblastic Anemia
  • Neural tube defects Neural tube defects Neural tube defects (NTDs) are the 2nd-most common type of congenital birth defects. Neural tube defects can range from asymptomatic (closed NTD) to very severe malformations of the spine or brain (open NTD). Neural tube defects are caused by the failure of the neural tube to close properly during the 3rd and 4th week of embryological development. Neural Tube Defects ( folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12)
  • Peripheral neuropathy Neuropathy Leprosy (especially B12)

Vitamin B1: Thiamin

Vitamin B1 is also known as thiamin. Thiamin deficiency causes the clinical syndromes of beriberi and Wernicke-Korsakoff syndrome Wernicke-Korsakoff syndrome 2 different syndromes that are different stages of the same disease including Wernicke’s encephalopathy and Korsakoff psychosis.Wernicke-Korsakoff syndrome is seen in patients with alcohol use disorder 8–10 times more than in the general population. Wernicke Encephalopathy and Korsakoff Syndrome.

Functions

  • Critical in energy metabolism:
    • An important cofactor for several key enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes in the Krebs cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation, including:
      • Pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis dehydrogenase
      • α-Ketoglutarate dehydrogenase 
    • Important for growth, development, and normal cell function
  • Nerve functions:
    • Required for the propagation Propagation Propagation refers to how the electrical signal spreads to every myocyte in the heart. Cardiac Physiology of cholinergic and serotonergic nerve impulses
    • Involved in myelin sheath maintenance
    • Deficiency produces neuropathy Neuropathy Leprosy and other neurologic symptoms.

Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption, metabolism, transport, and storage

  • Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption:
    • Primarily in the jejunum Jejunum The middle portion of the small intestine, between duodenum and ileum. It represents about 2/5 of the remaining portion of the small intestine below duodenum. Small Intestine: Anatomy and ileum Ileum The distal and narrowest portion of the small intestine, between the jejunum and the ileocecal valve of the large intestine. Small Intestine: Anatomy
    • Absorbed through both active transport Active transport The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy. The Cell: Cell Membrane and passive diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis
  • Thiamin diphosphate (TDP) (also known as thiamin pyrophosphate):
    • Metabolically active form of thiamin
    • Thiamin is transported in the blood in a dephosphorylated state.
    • Enters cells through active transport Active transport The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy. The Cell: Cell Membrane with an ATPase
    • Thiamin is activated to TDP via intracellular phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing.
  • Half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics and storage:
    • Highest concentrations of thiamin are found in:
      • Skeletal muscles Skeletal muscles A subtype of striated muscle, attached by tendons to the skeleton. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles. Muscle Tissue: Histology
      • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
      • Heart
      • Kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy
      • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
    • Half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics: 10–20 days
    • Storage capacity is limited → continuous intake is required to maintain normal levels.
  • Excretion: urine

Daily requirement

Typical RDAs for thiamin:

  • Infants: 0.2–0.3 mg/day 
  • Children: increases from 0.5 mg at age 1 to 0.9 mg at ages 9–13
  • Males ≥ 14 years: 1.2 mg
  • Females ≥ 14 years: 1.0–1.4 mg depending on age and pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care/ lactation Lactation The processes of milk secretion by the maternal mammary glands after parturition. The proliferation of the mammary glandular tissue, milk synthesis, and milk expulsion or let down are regulated by the interactions of several hormones including estradiol; progesterone; prolactin; and oxytocin. Breastfeeding status

Dietary sources

Thiamin is found in:

  • Whole grains and brown rice
  • Meat: pork and beef
  • Fish FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing and seafood
  • Legumes
  • Yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology
  • Fortified breads, cereals, rice, and infant formula

Deficiency: beriberi and Wernicke-Korsakoff syndrome Wernicke-Korsakoff syndrome 2 different syndromes that are different stages of the same disease including Wernicke’s encephalopathy and Korsakoff psychosis.Wernicke-Korsakoff syndrome is seen in patients with alcohol use disorder 8–10 times more than in the general population. Wernicke Encephalopathy and Korsakoff Syndrome

Thiamin deficiency manifests as 2 types of clinical syndromes: beriberi and Wernicke-Korsakoff syndrome Wernicke-Korsakoff syndrome 2 different syndromes that are different stages of the same disease including Wernicke’s encephalopathy and Korsakoff psychosis.Wernicke-Korsakoff syndrome is seen in patients with alcohol use disorder 8–10 times more than in the general population. Wernicke Encephalopathy and Korsakoff Syndrome.

Beriberi:

  • Rare in developed countries
  • Infantile beriberi:
    • Occurs in infants breastfed by thiamine-deficient mothers
    • Presents clinically with:
      • Fulminant cardiac syndrome: cardiomegaly Cardiomegaly Enlargement of the heart, usually indicated by a cardiothoracic ratio above 0. 50. Heart enlargement may involve the right, the left, or both heart ventricles or heart atria. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (heart failure) or several forms of cardiomyopathies. Ebstein’s Anomaly, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination, dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
      • Aphonic (soundless) crying
      • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
      • Agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus, purposeless movement, altered consciousness, and seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Dry beriberi:
  • Wet beriberi:
    • Signs and symptoms of cardiac involvement similar to infantile beriberi: cardiomegaly Cardiomegaly Enlargement of the heart, usually indicated by a cardiothoracic ratio above 0. 50. Heart enlargement may involve the right, the left, or both heart ventricles or heart atria. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (heart failure) or several forms of cardiomyopathies. Ebstein’s Anomaly, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Cardiomyopathy: Overview and Types, heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR), and peripheral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Neuropathy Neuropathy Leprosy

Wernicke-Korsakoff syndrome Wernicke-Korsakoff syndrome 2 different syndromes that are different stages of the same disease including Wernicke’s encephalopathy and Korsakoff psychosis.Wernicke-Korsakoff syndrome is seen in patients with alcohol use disorder 8–10 times more than in the general population. Wernicke Encephalopathy and Korsakoff Syndrome: 2 different syndromes that are different stages of the same disease.

  • Wernicke’s encephalopathy Encephalopathy Hyper-IgM Syndrome:
    • An acute encephalopathy Encephalopathy Hyper-IgM Syndrome requiring emergent treatment (20% mortality Mortality All deaths reported in a given population. Measures of Health Status without treatment)
    • Symptoms include: peripheral neuropathy Neuropathy Leprosy, ocular abnormalities (e.g., nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism, ophthalmoplegia Ophthalmoplegia Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. Orbital and Preseptal Cellulitis), ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia, aphasia Aphasia A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. Ischemic Stroke, and confusion
  • Korsakoff psychosis:
  • Wernicke-Korsakoff syndrome Wernicke-Korsakoff syndrome 2 different syndromes that are different stages of the same disease including Wernicke’s encephalopathy and Korsakoff psychosis.Wernicke-Korsakoff syndrome is seen in patients with alcohol use disorder 8–10 times more than in the general population. Wernicke Encephalopathy and Korsakoff Syndrome is seen in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder 8–10 times more than in the general population. 
A patient with wernicke encephalopathy showing hyperintensity of the periaqueductal gray substancea patient with wernicke encephalopathy showing hyperintensity of the periaqueductal gray substance

A patient with Wernicke encephalopathy Wernicke encephalopathy An acute neurological disorder characterized by the triad of ophthalmoplegia, ataxia, and disturbances of mental activity or consciousness. Eye movement abnormalities include nystagmus, external rectus palsies, and reduced conjugate gaze. Thiamine deficiency and chronic alcoholism are associated conditions. Pathologic features include periventricular petechial hemorrhages and neuropil breakdown in the diencephalon and brainstem. Chronic thiamine deficiency may lead to Korsakoff syndrome. Wernicke Encephalopathy and Korsakoff Syndrome showing hyperintensity of the periaqueductal gray substance

Image: “Fig3: FLAIR FLAIR Magnetic Resonance Imaging (MRI) axial Axial Computed Tomography (CT) shows hyperintensity of the periaqueductal grey” by Busani S. et al AL Amyloidosis. License: CC BY 4.0

Therapeutic uses and clinical relevance

  • Thiamin deficiency can occur in:
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with alcoholism Alcoholism A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. Wernicke Encephalopathy and Korsakoff Syndrome, due to poor dietary intake
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship on total parenteral nutrition Total parenteral nutrition The delivery of nutrients for assimilation and utilization by a patient whose sole source of nutrients is via solutions administered intravenously, subcutaneously, or by some other non-alimentary route. The basic components of tpn solutions are protein hydrolysates or free amino acid mixtures, monosaccharides, and electrolytes. Components are selected for their ability to reverse catabolism, promote anabolism, and build structural proteins. IPEX Syndrome (TPN) without adequate supplementation
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who have undergone bariatric surgery Bariatric surgery Bariatric surgery refers to a group of invasive procedures used to surgically reduce the size of the stomach to produce early satiety, decrease food intake (restrictive type) and/or alter digestion, and artificially induce malabsorption of nutrients (malabsorptive type). The ultimate goal of bariatric surgery is drastic weight loss. Bariatric Surgery, due to malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS, possibly due to malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries in a catabolic state
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with rapidly progressing hematologic malignancies
  • Treatment is with IV then oral thiamine supplementation depending on the severity of disease.
  • Symptoms of toxicity Toxicity Dosage Calculation: none identified (the kidney can rapidly clear most excess thiamin, and thiamin is not stored in large amounts in the body)

Vitamin B2: Riboflavin

Vitamin B2 is known as riboflavin, and deficiency is rarely seen in the United States.

Functions

  • Involved in many metabolic pathways as an essential component of coenzymes Coenzymes Small molecules that are required for the catalytic function of enzymes. Many vitamins are coenzymes. Basics of Enzymes
  • Involved in energy production in the Krebs cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation
  • Catalyzes multiple oxidation-reduction reactions
  • Important for normal growth, development, and cell function

Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption, metabolism, transport, and storage

  • Hydrolysis Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water. Proteins and Peptides of dietary riboflavin into free riboflavin in the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy via gastric acid Gastric acid Hydrochloric acid present in gastric juice. Gastroesophageal Reflux Disease (GERD) and proteolytic enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
  • Passive absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption via a transport system in the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy (this system can become saturated)
  • Free riboflavin is bound to albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests and some immunoglobulins Immunoglobulins Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions in the blood.
  • Transported to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy via the bloodstream
  • Free riboflavin is metabolized to its active form, flavin adenine Adenine A purine base and a fundamental unit of adenine nucleotides. Nucleic Acids dinucleotide (FAD), via intracellular ATP-dependent phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing.
  • Stored as flavoproteins (flavin complexed with proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis) in limited amounts, primarily in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy

Daily requirement

  • Infants: 0.3–0.4 mg/day 
  • Children 1–13 years: 0.5–0.9 mg/day
  • Adults: 1.0–1.6 mg/day depending on exact age, sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria, and pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care/ lactation Lactation The processes of milk secretion by the maternal mammary glands after parturition. The proliferation of the mammary glandular tissue, milk synthesis, and milk expulsion or let down are regulated by the interactions of several hormones including estradiol; progesterone; prolactin; and oxytocin. Breastfeeding status

Dietary sources

  • Milk
  • Eggs
  • Organ meats (e.g., liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy), lean LEAN Quality Measurement and Improvement meat, and fish FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing
  • Green vegetables (e.g., asparagus, broccoli, spinach)
  • Yeasts
  • Fortified cereals and breads

Deficiency

  • Symptoms:
    • Stomatitis Stomatitis Stomatitis is a general term referring to inflammation of the mucous membranes of the mouth, which may include sores. Stomatitis can be caused by infections, autoimmune disorders, allergic reactions, or exposure to irritants. The typical presentation may be either solitary or a group of painful oral lesions. Stomatitis, cheilitis Cheilitis Inflammation of the lips. It is of various etiologies and degrees of pathology. Oral Cancer, and/or glossitis ( inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the mouth, lips Lips The lips are the soft and movable most external parts of the oral cavity. The blood supply of the lips originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy, and/or tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy)
    • Pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis (“ sore throat Sore throat Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis”)
    • Seborrheic dermatitis Seborrheic dermatitis Seborrheic dermatitis is a common chronic, relapsing skin disorder that presents as erythematous plaques with greasy, yellow scales in susceptible areas (scalp, face, and trunk). Seborrheic dermatitis has a biphasic incidence, occurring in two peaks: first in infants, then in adolescence and early adulthood. Seborrheic Dermatitis 
    • Cataracts
    • Normochromic normocytic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
  • Due to inadequate intake in:
    • Vegan diets, especially in athletes
    • Heavy alcohol use
    • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with anorexia nervosa Anorexia Nervosa Anorexia nervosa is an eating disorder marked by self-imposed starvation and inappropriate dietary habits due to a morbid fear of weight gain and disturbed perception of body shape and weight. Patients have strikingly low BMI and diverse physiological and psychological complications. Anorexia Nervosa
    • Malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion in celiac and other intestinal diseases
    • Long-term use of barbiturates Barbiturates A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are gaba modulators used as hypnotics and sedatives, as anesthetics, or as anticonvulsants. Intravenous Anesthetics
  • Rarely can be seen in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a condition known as Brown-Vialetto-Van Laere syndrome, which results from a congenital Congenital Chorioretinitis defect in riboflavin-dependent enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes.
Angular stomatitis due to riboflavin deficiency

Angular stomatitis Stomatitis Stomatitis is a general term referring to inflammation of the mucous membranes of the mouth, which may include sores. Stomatitis can be caused by infections, autoimmune disorders, allergic reactions, or exposure to irritants. The typical presentation may be either solitary or a group of painful oral lesions. Stomatitis due to riboflavin deficiency

Image: “This image depicted a frontal Frontal The bone that forms the frontal aspect of the skull. Its flat part forms the forehead, articulating inferiorly with the nasal bone and the cheek bone on each side of the face. Skull: Anatomy view of the lower half of a patient’s face” by Public Health Image Library (PHIL). License: Public Domain

Therapeutic uses and clinical relevance

  • Therapeutic replacement in cases of deficiency due to inadequate intake
  • HIV HIV Anti-HIV Drugs patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with lactic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis due to certain antiretroviral medications (lactic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis can be reversed by riboflavin therapy)
  • Limited evidence suggests a role for its use in migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache prevention
  • Symptoms of toxicity Toxicity Dosage Calculation: none identified (saturation of the absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption mechanisms and rapid excretion by the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy prevents toxic accumulation)

Vitamin B3: Niacin

Niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs is the generic name for a group of compounds including nicotinic acid Nicotinic acid A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and nadp. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs, nicotinamide, and related derivatives. It is widely distributed in plant and animal foods. Niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs deficiency causes the clinical condition known as pellagra.

Functions

Niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs is required for most metabolic processes in the body:

  • Plays a critical role in oxidative and reduction reactions through its active forms:
    • NAD NAD+ A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway
      • Generally involved in catabolic reactions
      • Transfers energy from carbohydrates Carbohydrates A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of cn(H2O)n. The largest class of organic compounds, including starch; glycogen; cellulose; polysaccharides; and simple monosaccharides. Basics of Carbohydrates, fats Fats The glyceryl esters of a fatty acid, or of a mixture of fatty acids. They are generally odorless, colorless, and tasteless if pure, but they may be flavored according to origin. Fats are insoluble in water, soluble in most organic solvents. They occur in animal and vegetable tissue and are generally obtained by boiling or by extraction under pressure. They are important in the diet (dietary fats) as a source of energy. Energy Homeostasis, and proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis to ATP
    • NAD NAD+ A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes (NADP): 
  • Catalyzes over 400 enzymatic reactions, more than any other vitamin-derived coenzyme
  • Participates in antioxidant function
  • Maintains genome Genome The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics integrity, affects gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics expression, and is involved in cellular communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence
  • Nerve function
  • Cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism production

Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption, metabolism, transport, and storage

  • Most dietary niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs is in the form of NAD NAD+ A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway and NADP.
  • Dietary NAD NAD+ A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway and NADP are hydrolyzed 1st to nicotinamide and then some is converted to nicotinic acid Nicotinic acid A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and nadp. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs by intestinal microbes.
  • Nicotinamide and nicotinic acid Nicotinic acid A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and nadp. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs are absorbed in the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy via passive and facilitated diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis.
  • Taken up by most cells in the body, where they are converted back to NAD NAD+ A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway and NADP.
  • NAD NAD+ A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway and NADP are most concentrated in the muscles and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy.
  • Excess niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs:
    • Some is taken up by RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology (small storage form).
    • The rest is methylated and excreted in the urine.
  • Tryptophan can also be converted to nicotinamide in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy using vitamin B6 as a cofactor.

Daily requirement

  • Infants and children: 2 mg/day starting at birth and increasing to 12 mg/day as the child grows 
  • Males ≥ 14 years of age: 16 mg/day
  • Females ≥ 14 years of age: 14 mg/day; 17–18 mg/day while pregnant/ lactating

Dietary sources

  • Meat, especially liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
  • Fish FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing (e.g., salmon, tuna)
  • Poultry
  • Legumes, nuts, and seeds
  • Grains (e.g., brown rice)
  • Fortified cereals, breads, and infant formulas
  • Also synthesized from tryptophan (ability varies significantly between individuals)

Deficiency: pellagra

The clinical syndrome associated with niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs deficiency is called pellagra.

  • Symptoms of pellagra (“the 4 Ds”):
    • Dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema): photosensitivity Photosensitivity Tetracyclines leading to a symmetric, rough pigmented rash Rash Rocky Mountain Spotted Fever in sun-exposed areas
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
    • Dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders: may include depression progressing to psychosis with memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment loss
    • Death (rare)
  • Pellagra is rare in the United States except in certain at-risk populations:
    • Alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder
    • Complication of bariatric surgery Bariatric surgery Bariatric surgery refers to a group of invasive procedures used to surgically reduce the size of the stomach to produce early satiety, decrease food intake (restrictive type) and/or alter digestion, and artificially induce malabsorption of nutrients (malabsorptive type). The ultimate goal of bariatric surgery is drastic weight loss. Bariatric Surgery
    • Anorexia nervosa Anorexia Nervosa Anorexia nervosa is an eating disorder marked by self-imposed starvation and inappropriate dietary habits due to a morbid fear of weight gain and disturbed perception of body shape and weight. Patients have strikingly low BMI and diverse physiological and psychological complications. Anorexia Nervosa 
    • Malabsorptive conditions
    • Carcinoid syndrome Carcinoid syndrome A symptom complex associated with carcinoid tumor and characterized by attacks of severe flushing of the skin, diarrheal watery stools, bronchoconstriction, sudden drops in blood pressure, edema, and ascites. The carcinoid tumors are usually located in the gastrointestinal tract and metastasize to the liver. Symptoms are caused by tumor secretion of serotonin, prostaglandins, and other biologically active substances. Cardiac manifestations constitute carcinoid heart disease. Carcinoid Tumors and Syndrome
    • Hartnup disease: an autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder resulting in defective absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of tryptophan
Characteristic skin rash associated with pellagra malabsorption

Characteristic skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions rash Rash Rocky Mountain Spotted Fever associated with pellagra

Image: “This child has the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions rash Rash Rocky Mountain Spotted Fever associated with pellagra” by CDC. License: Public Domain

Therapeutic uses and clinical relevance

  • Used to treat pellagra (along with a B-complex vitamins or yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology product Product A molecule created by the enzymatic reaction. Basics of Enzymes)
  • Niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs has lipid-lowering properties, especially total and LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism:
    • Provides no significant protection against cardiovascular disease
    • Rarely used because more modern medications that are more effective at reducing cardiovascular events are available.

Toxicity Toxicity Dosage Calculation

  • Not seen with foods containing niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs
  • At pharmacologic doses (1000–3000 mg/day), side effects include:
    • Flushing
    • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
    • GI effects:
      • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics
      • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
      • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
    • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) and hives Hives Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives) 
    • Blurred vision Vision Ophthalmic Exam and macular edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Impaired glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance tolerance Tolerance Pharmacokinetics and Pharmacodynamics and insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
    • Hepatotoxicity Hepatotoxicity Acetaminophen and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy failure

Vitamin B5: Pantothenic Acid

Vitamin B5 is also known as pantothenic acid.

Functions

The biologically active form of vitamin B5 is coenzyme A (CoA):

  • Involved in many acetylation Acetylation Formation of an acetyl derivative. Chloramphenicol reactions in the body:
  • Involved in the synthesis Synthesis Polymerase Chain Reaction (PCR) and/or degradation of:
    • Carbohydrates Carbohydrates A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of cn(H2O)n. The largest class of organic compounds, including starch; glycogen; cellulose; polysaccharides; and simple monosaccharides. Basics of Carbohydrates, proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids, and fatty acids Fatty acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated. Fatty Acids and Lipids
    • Cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism and steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors
    • Heme A Heme A Part of complex IV of electron transport system. Heme Metabolism
    • Vitamins A and D
  • Involved in the activation and inactivation of many peptide hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types, including adrenocorticotropic hormone Adrenocorticotropic hormone An anterior pituitary hormone that stimulates the adrenal cortex and its production of corticosteroids. Acth is a 39-amino acid polypeptide of which the n-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotropic activity. Upon further tissue-specific processing, acth can yield alpha-msh and corticotropin-like intermediate lobe peptide (clip). Adrenal Hormones (ACTH)

Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption, metabolism, transport, and storage

  • About 85% of dietary pantothenic acid is in CoA or phosphopantetheine form → converted to pantothenic acid by digestive enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes in the intestines
  • Intestinal flora can also produce pantothenic acid in unknown amounts.
  • Absorbed in the intestine and delivered to the blood by active transport Active transport The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy. The Cell: Cell Membrane
  • Transported by RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology throughout the body
  • Stored in tissues in the form of CoA and other carrier Carrier Vaccination proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis

Daily requirement

  • Infants: 1.7–1.8 mg/day 
  • Children: increases from 2 mg/day at age 1 to 4 mg/day at age 13
  • Adults: 5 mg, slightly higher during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care and lactation Lactation The processes of milk secretion by the maternal mammary glands after parturition. The proliferation of the mammary glandular tissue, milk synthesis, and milk expulsion or let down are regulated by the interactions of several hormones including estradiol; progesterone; prolactin; and oxytocin. Breastfeeding

Dietary sources

  • Shiitake mushrooms Mushrooms Mycology
  • Sunflower seeds
  • Egg yolks
  • Organ meats ( liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and kidney)
  • Beef and chicken
  • Broccoli
  • Dairy
  • Whole grains
  • Fortified cereals, breads, and formula

Clinical relevance

  • Deficiency:
    • Rarely seen because of wide distribution in food and synthesis Synthesis Polymerase Chain Reaction (PCR) by the gut flora, but can be seen in people with severe malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries (e.g., during war, famine)
    • Presents with paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome and dysesthesias of the hands and feet, known as burning feet syndrome
  • Not currently recommended in the treatment of any specific condition other than as part of a generally healthy diet
  • Symptoms of toxicity Toxicity Dosage Calculation: none known 

Vitamin B6: Pyridoxine

Vitamin B6 is the generic name for 6 compounds, including pyridoxine, pyridoxal, pyridoxamine, and their phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes esters.

Functions

Pyridoxal 5´-phosphate (PLP) and pyridoxamine 5´-phosphate (PMP) are the active forms of vitamin B6 and have the following functions:

  • Involved in many metabolic processes, mostly related to protein metabolism
  • Required for the production of RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology
  • Used in glycogenolysis Glycogenolysis The release of glucose from glycogen by glycogen phosphorylase (phosphorolysis). The released glucose-1-phosphate is then converted to glucose-6-phosphate by phosphoglucomutase before entering glycolysis. Glycogenolysis is stimulated by glucagon or epinephrine via the activation of phosphorylase kinase. Glycogen Metabolism and gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis
  • Used in the transamination Transamination Transamination is the transfer of an amino group from an alpha-AA to an alpha-keto acid, which is an AA with an alpha-keto group (=O) instead of an alpha-amino group (NH2). Catabolism of Amino Acids process (converting essential amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids to nonessential amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids)
  • Take part in neurotransmitter production
  • Cofactor for the production of vitamin B3 ( niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs)

Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption, metabolism, transport, and storage

  • Phosphorylated forms of the vitamin are metabolized to free vitamin B6 before they absorbed.
  • Absorbed by passive diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis in the jejunum Jejunum The middle portion of the small intestine, between duodenum and ileum. It represents about 2/5 of the remaining portion of the small intestine below duodenum. Small Intestine: Anatomy
  • Phosphorylated to active forms in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
  • No significant storage in the body

Daily requirement

  • Infants: 0.1–0.3 mg/day 
  • Children 1–8 years of age: 0.5–0.6 mg/day
  • Children 9–13 years of age: 1.0 mg/day
  •  Adults: 1.3–2.0 mg/day for adults, based on sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria, age, and pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care/ lactation Lactation The processes of milk secretion by the maternal mammary glands after parturition. The proliferation of the mammary glandular tissue, milk synthesis, and milk expulsion or let down are regulated by the interactions of several hormones including estradiol; progesterone; prolactin; and oxytocin. Breastfeeding status

Dietary sources

Found in a wide variety of foods:

  • Garbanzo beans
  • Poultry
  • Fish FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing
  • Organ meats (e.g., beef liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy)
  • Fortified cereals
  • Potatoes and other starchy vegetables
  • Bananas

Deficiency

  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with certain conditions are at risk for vitamin B6 deficiency:
    • Undergoing isoniazid Isoniazid Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Antimycobacterial Drugs treatment for tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
    • Impaired renal function and/or diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
    • Autoimmune disease, particularly rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis
    • Malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion conditions: inflammatory bowel disease, celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease
    • Alcohol abuse
    • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
    • Breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer and Hodgkin lymphoma Hodgkin lymphoma Hodgkin lymphoma (HL) is a malignancy of B lymphocytes originating in the lymph nodes. The pathognomonic histologic finding of HL is a Hodgkin/Reed-Sternberg (HRS) cell (giant multinucleated B cells with eosinophilic inclusions). The disease presents most commonly with lymphadenopathy, night sweats, weight loss, fever, splenomegaly and hepatomegaly. Hodgkin Lymphoma
  • Symptoms of pyridoxine deficiency:
    • Stomatitis Stomatitis Stomatitis is a general term referring to inflammation of the mucous membranes of the mouth, which may include sores. Stomatitis can be caused by infections, autoimmune disorders, allergic reactions, or exposure to irritants. The typical presentation may be either solitary or a group of painful oral lesions. Stomatitis, cheilitis Cheilitis Inflammation of the lips. It is of various etiologies and degrees of pathology. Oral Cancer, and/or glossitis
    • Dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema)
    • Confusion, irritability, and/or depression
    • Decreased immunity
    • Microcytic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types

Therapeutic uses and clinical relevance

  • Vitamin B6 is recommended as 1st-line therapy in the treatment of nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care.
  • Vitamin B6 supplements have been studied in (but are not currently recommended for) the treatment of:
    • Cancer
    • Cardiovascular disease
    • Cognitive decline

Toxicity Toxicity Dosage Calculation

Vitamin B6 is among the only water-soluble vitamins that can cause significant toxicity Toxicity Dosage Calculation if taken in high doses.

  • Not found due to regular Regular Insulin dietary intake
  • High-dose supplements can cause:
    • Severe and progressive sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology neuropathy Neuropathy Leprosy 
    • Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia
    • Painful skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions
    • Photosensitivity Photosensitivity Tetracyclines
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and heartburn Heartburn Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. Gastroesophageal Reflux Disease (GERD)

Vitamin B7: Biotin

Functions

Cofactor for several carboxylases that catalyze critical steps in the metabolism of fatty acids Fatty acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated. Fatty Acids and Lipids, glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance, and amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids. Biotin is involved in:

Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption, synthesis Synthesis Polymerase Chain Reaction (PCR), and storage

  • In foods, biotin is bound to proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis.
  • Released from proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis and converted into its free form by GI enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
  • Also synthesized by gut microbes
  • Absorbed in the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy
  • Stored in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
  • Excretion:
    • Excess production in the gut is excreted in the feces.
    • Excess biotin in the serum is excreted in the urine.

Daily requirement

  • Infants: 5–6 µg/day 
  • Children: 6–12 µg/day
  • Teens: 20–25 µg/day 
  • Adults: 30 µg/day (35 µg/day during lactation Lactation The processes of milk secretion by the maternal mammary glands after parturition. The proliferation of the mammary glandular tissue, milk synthesis, and milk expulsion or let down are regulated by the interactions of several hormones including estradiol; progesterone; prolactin; and oxytocin. Breastfeeding)

Dietary sources

  • Egg yolk
  • Molasses/ yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology
  • Soybean products/legumes
  • Beef liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy

Deficiency

Dietary deficiency is extremely rare.

  • Symptoms:
    • Thinning and loss of hair (all over the body)
    • Dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema)
    • Conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis
    • Brittle nails
    • Neurologic symptoms:
      • Lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia
      • Paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome
      • Altered mental status Altered Mental Status Sepsis in Children
      • Hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
  • Biotin deficiency may occur in:
    • Chronic alcoholism Alcoholism A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. Wernicke Encephalopathy and Korsakoff Syndrome
    • Pregnant and breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding women 
    • Rare genetic conditions related to biotin processing

Clinical relevance

  • Symptoms of toxicity Toxicity Dosage Calculation: none known
  • High doses of biotin supplements can interfere with lab testing assays for:
    • Thyroid function tests Thyroid Function Tests Blood tests used to evaluate the functioning of the thyroid gland. Ion Channel Myopathy
    • Ferritin Ferritin Iron-containing proteins that are widely distributed in animals, plants, and microorganisms. Their major function is to store iron in a nontoxic bioavailable form. Each ferritin molecule consists of ferric iron in a hollow protein shell (apoferritins) made of 24 subunits of various sequences depending on the species and tissue types. Hereditary Hemochromatosis
    • Troponin
    • Digoxin Digoxin A cardiotonic glycoside obtained mainly from digitalis lanata; it consists of three sugars and the aglycone digoxigenin. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. Cardiac Glycosides levels
    • Testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens
    • Progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones
    • BNP BNP A peptide that is secreted by the brain and the heart atria, stored mainly in cardiac ventricular myocardium. It can cause natriuresis; diuresis; vasodilation; and inhibits secretion of renin and aldosterone. It improves heart function. It contains 32 amino acids. Renal Sodium and Water Regulation
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should abstain from taking high-dose biotin supplements (promoted as vitamins for hair, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, and nails) for 3–4 days before lab testing.

Vitamin C: Ascorbic Acid

Vitamin C is an important antioxidant and is critical in wound healing Wound healing Wound healing is a physiological process involving tissue repair in response to injury. It involves a complex interaction of various cell types, cytokines, and inflammatory mediators. Wound healing stages include hemostasis, inflammation, granulation, and remodeling. Wound Healing and in the synthesis Synthesis Polymerase Chain Reaction (PCR) of collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology, among its many functions. Vitamin C deficiency causes the clinical condition scurvy.

Functions

  • Required for the synthesis Synthesis Polymerase Chain Reaction (PCR) of:
    • Collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology → essential for wound healing Wound healing Wound healing is a physiological process involving tissue repair in response to injury. It involves a complex interaction of various cell types, cytokines, and inflammatory mediators. Wound healing stages include hemostasis, inflammation, granulation, and remodeling. Wound Healing and connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology
    • Neurotransmitters
    • Carnitine Carnitine A constituent of striated muscle and liver. It is an amino acid derivative and an essential cofactor for fatty acid metabolism. Fatty Acid Metabolism
  • Has antioxidant properties, along with vitamins A and E
  • Improves absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements from diet
  • Is a cofactor in the reduction of folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12 to dihydrofolate and tetrahydrofolate Tetrahydrofolate Sulfonamides and Trimethoprim
  • Involved in many additional physiologic processes:
    • Protein metabolism
    • Fatty acid transport
    • Immune function

Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption, transport, and storage

  • Absorbed in the distal small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy via an active transporter
  • Blood levels are regulated by renal excretion of excess vitamin C in the urine.
  • Some storage in the adrenal glands Adrenal Glands The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. Adrenal Glands: Anatomy, brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification, and eyes

Daily requirement

  • Infants: 45–50 mg/day 
  • Children 1–13 years of age: 15–45 mg/day
  • People ≥ 14 years of age: 65–90 mg/day based on age, sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria, and pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care status
  • Lactating females: 115–120 mg/day 

Dietary sources

  • Citrus fruits
  • Other fruits:
    • Kiwifruit
    • Strawberries
    • Cantaloupe
  • Vegetables:
    • Red and green peppers
    • Cabbage
    • Brussels sprouts
    • Broccoli
    • Cauliflower
    • Potatoes
    • Tomatoes

Deficiency: scurvy

Vitamin C deficiency leads to the clinical condition called scurvy and can be seen as soon as 1–3 months with little to no intake. 

  • Symptoms:
    • Delayed wound healing Wound healing Wound healing is a physiological process involving tissue repair in response to injury. It involves a complex interaction of various cell types, cytokines, and inflammatory mediators. Wound healing stages include hemostasis, inflammation, granulation, and remodeling. Wound Healing
    • Petechiae Petechiae Primary Skin Lesions, purpura, and ecchymoses
    • Gingivitis Gingivitis Inflammation of gum tissue (gingiva) without loss of connective tissue. Chédiak-Higashi Syndrome with bleeding and loose teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth: Anatomy
    • Arthralgias
    • Follicular hyperkeratosis Hyperkeratosis Ichthyosis Vulgaris
    • Iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements deficiency anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types due to ↓ iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption
  • Populations at risk:
    • Insufficient intake of fruits and vegetables:
      • Drug or alcohol abuse disorders
      • Poverty
      • Institutionalized people
      • Chronically ill patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
    • Cigarette smokers have lower levels of vitamin C (due to ↑ oxidative stress Oxidative stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products. Cell Injury and Death) → require increased intake
Child with vitamin c deficiency

Child with vitamin C deficiency:
A: Contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing and ecchymoses
B: Hyperkeratosis Hyperkeratosis Ichthyosis Vulgaris and follicular purpura with corkscrew hairs (arrow)
C: Hemorrhagic gingivitis Gingivitis Inflammation of gum tissue (gingiva) without loss of connective tissue. Chédiak-Higashi Syndrome and neurotic excoriations Excoriations Excoriation is a linear abrasion produced by mechanical means (scratching, rubbing, or picking) that usually involves only the epidermis but can reach the papillary dermis. Secondary Skin Lesions (arrow)

Image: “Childhood scurvy: an unusual cause of refusal to walk in a child” by Alqanatish JT, Alqahtani F, Alsewairi WM, Al-kenaizan S. License: CC BY 4.0

Therapeutic uses and clinical relevance

  • The only therapeutic use of vitamin C is to treat scurvy.
  • Symptoms of toxicity Toxicity Dosage Calculation (due to excess supplementation, not dietary intake):
    • Kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis
    • Abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea

References

  1. Pazirandeh, S., Burns, D.L. (2020). Overview of water-soluble vitamins. UpToDate. Retrieved May 7, 2021, from https://www.uptodate.com/contents/overview-of-water-soluble-vitamins
  2. National Institutes of Health Office of Dietary Supplements. (2021). Fact sheets for health professionals: thiamin, riboflavin, niacin, pantothenic acid, vitamin B6, biotin, and vitamin C. Retrieved May 12, 2021, from https://ods.od.nih.gov/factsheets/list-all/
  3. Goetzl, L.M. (2020). Folic acid supplementation in pregnancy. UpToDate. Retrieved May 12, 2021, from https://www.uptodate.com/contents/folic-acid-supplementation-in-pregnancy
  4. Fairfield, K.M. (2019). Vitamin supplementation in disease prevention. UpToDate. Retrieved May 12, 2021, from https://www.uptodate.com/contents/vitamin-supplementation-in-disease-prevention

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