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Fat-soluble Vitamins and their Deficiencies

Fat-soluble vitamins are absorbed and stored in adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or "brite" adipose tissue, which is a transitional form. Adipose Tissue: Histology (fat) and 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. These vitamins can be released from storage and used when necessary. The 4 important fat-soluble vitamins are A, D, E, and K. Each vitamin has its own function, and deficiencies can lead to significant clinical manifestations. Diagnosis of deficiencies is by clinical presentation and lab testing, and management of vitamin deficiency is with supplementation. Because these vitamins are fat-soluble and stored in the body, overuse of supplemental vitamins may lead to toxicity Toxicity Dosage Calculation and adverse effects, especially with vitamins A and D.

Last updated: Sep 8, 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. They are divided into water-soluble and fat-soluble vitamins. 

  • The most clinically important fat-soluble vitamins are the vitamins A, D, E, and K. 
  • Deficiencies and overuse of these vitamins can lead to clinical manifestations.
  • 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. 
  • There may be special circumstances in infants or elderly or pregnant patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.

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 and storage

Fat-soluble vitamins are absorbed from the intestines with fat. In general, this process requires:

  • Lingual and gastric lipases Lipases An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Lipid Metabolism
  • Bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy salts for solubilization and production of micelles Micelles Particles consisting of aggregates of molecules held loosely together by secondary bonds. The surface of micelles are usually comprised of amphiphatic compounds that are oriented in a way that minimizes the energy of interaction between the micelle and its environment. Liquids that contain large numbers of suspended micelles are referred to as emulsions. Malabsorption and Maldigestion
  • Pancreatic lipases Lipases An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Lipid Metabolism
  • Intestinal mucosal 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
  • Packaging into chylomicrons within the intestinal mucosal cells
  • Chylomicrons are sent 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 lymphatics for processing.
  • Fat-soluble vitamins are stored in adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or “brite” adipose tissue, which is a transitional form. Adipose Tissue: Histology.

Groups at higher risk for deficiency

For all of the fat-soluble vitamins, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with fat-malabsorption issues are at higher risk for deficiency. These conditions include:

  • Pancreatic insufficiency (results in insufficient lipase Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Malabsorption and Maldigestion) from cystic fibrosis Cystic fibrosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis, chronic pancreatitis Chronic pancreatitis Chronic pancreatitis is due to persistent inflammation, fibrosis, and irreversible cell damage to the pancreas, resulting in a loss of endocrine and exocrine gland function. The most common etiologies are alcohol abuse and pancreatic duct obstruction. Patients often present with recurrent epigastric abdominal pain, nausea, and features of malabsorption syndrome (diarrhea, steatorrhea, and weight loss). Chronic Pancreatitis, or pancreatectomy 
  • Cholestatic 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 disease (results in insufficient bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy)
  • 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
  • Crohn disease
  • Short bowel syndrome Short bowel syndrome Short bowel syndrome is a malabsorptive condition most commonly associated with extensive intestinal resection for etiologies such as Crohn’s disease, bowel obstruction, trauma, radiation therapy, and vascular insufficiency. The short length of bowel results in insufficient surface area for fluid and electrolyte absorption. Short Bowel Syndrome
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a history of some types 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

Mnemonic

To remember the fat-soluble vitamins, use the saying: “The Fat cat is in the ADEK (pronounce it like attic).”

Vitamin A: Retinoids

Forms

Known as retinoids, vitamin A comes in several active forms and several precursor forms:

  • Retinol and retinyl esters: storage form
  • Retinal: part of the rhodopsin complex in rod cells (responsible for light and motion detection)
  • Retinoic acid: important for cell differentiation
  • Beta-carotene: a vitamin A precursor

Functions

  • Vision Vision Ophthalmic Exam
    • Rhodopsin and retinal play important roles in night vision Vision Ophthalmic Exam.
    • Retinal starts in the all-trans configuration → converted to the 11- cis CIS Multiple Sclerosis-retinal configuration when a photon is absorbed
    • This conformational change activates transducin, which ultimately results in the closing of calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channels Channels The Cell: Cell Membrane → decreases neurotransmitter release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology
    • ↓ Neurotransmitters: signal to the 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 that light has been detected
    • To remember that vitamin A is important for vision Vision Ophthalmic Exam, think “ retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy” in the eye.
  • Cell differentiation: 
    • Retinoic acid 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 cell differentiation.
    • Critical to the development of the eyes, heart, lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: 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
  • Vitamin A is also involved in:
    • 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 epithelialization Epithelialization Anal Fistula
    • Growth
    • Immune function
    • Reproduction
  • Vitamin A is an antioxidant.
Steps in light detection vitamin a

Steps in light detection in the cone or rods cells mediated by the retinal form of vitamin A, found in rhodopsin
cGMP cGMP Guanosine cyclic 3. Phosphodiesterase Inhibitors: cyclic guanosine monophosphate Guanosine monophosphate A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature. Purine and Pyrimidine Metabolism
GDP: guanosine diphosphate
GMP: guanosine monophosphate Guanosine monophosphate A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature. Purine and Pyrimidine Metabolism
GTP: guanosine triphosphate

Image by Kevin Ahern, PhD.

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

  • Different forms of vitamin A 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 from dietary sources. 
  • These different forms are hydrolyzed into retinol at the mucosal brush border Brush border Tubular System.
  • Retinols are re-esterified, incorporated into chylomicrons, and then excreted into the lymphatics, where they are moved 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.
  • Most of the total body retinol is 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.

Daily requirements

Typical RDAs for vitamin A are: 

  • Children ≤ 8 years of age (varies based on exact age): 300–500 µg 
  • Children 9–13: 600 µg
  • Females ≥ 14 years: 700 µg (higher if pregnant or lactating)
  • Males ≥ 14 years: 900 µg

Dietary sources

Mostly from yellow and orange foods: 

  • Highest sources: 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 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 oil
  • Other animal sources:
    • Dairy
    • Egg yolks
  • Orange plants Plants Cell Types: Eukaryotic versus Prokaryotic:
    • Carrots
    • Sweet potatoes
    • Pumpkin
  • Other red/yellow plants Plants Cell Types: Eukaryotic versus Prokaryotic:
    • Cantaloupe
    • Mangos
    • Tomatoes
    • Red bell peppers
  • Green, leafy vegetables:
    • Spinach
    • Broccoli

Symptoms of deficiency

The primary symptoms of clinical concern are related to vision Vision Ophthalmic Exam:

  • Visual symptoms:
    • Poor night vision Vision Ophthalmic Exam (nyctalopia) 
    • Dry eye ( xerophthalmia Xerophthalmia Dryness of the eye surfaces caused by deficiency of tears or conjunctival secretions. It may be associated with vitamin A deficiency, trauma, or any condition in which the eyelids do not close completely. Sjögren’s Syndrome
    • Blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity
  • Hyperkeratosis Hyperkeratosis Ichthyosis Vulgaris (scaly 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 destruction of hair follicles 
  • Poor bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types growth due to decreased endochondral bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types formation and osteoblastic activity
  • Impaired immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs function due to direct effect on T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions

Groups at higher risk for deficiency

Vitamin A deficiency is uncommon in developed countries, but it may be encountered in the following groups:

  • Preterm infants
  • Children and pregnant and lactating women in developing countries
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with fat malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion

Therapeutic uses

Forms of vitamin A are used in treatments for the following conditions:

  • Acute myeloid leukemia Acute Myeloid Leukemia Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Acute Myeloid Leukemia
  • Acne: found in topical and oral medications
  • Measles Measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus (for children in developing countries; appears to reduce mortality Mortality All deaths reported in a given population. Measures of Health Status)

Toxicity Toxicity Dosage Calculation

Typically occurs only with chronic ingestion of large amounts of synthetic or animal sources of vitamin A (approximately 10× the RDA). 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 beta-carotene (plant sources) is highly regulated and is extremely unlikely to cause toxicity Toxicity Dosage Calculation. Symptoms of toxicity Toxicity Dosage Calculation include:

  • 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
  • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
  • Vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo
  • Blurred vision Vision Ophthalmic Exam
  • Teratogenicity if used in pregnant patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (e.g., isotretinoin used in acne treatment Acne Treatment Acne Vulgaris)
  • Hepatotoxicity Hepatotoxicity Acetaminophen

Vitamin D: Calciferol

Technically, vitamin D is a hormone because it is made in the body, while actual vitamins are not made in the body. Vitamin D3 is made in 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 of all vertebrates when they are exposed to the sun, while D2 is produced by some fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology (e.g., mushrooms Mushrooms Mycology) and can be consumed in food or supplement form.

Functions

Vitamin D’s most important impacts are related to calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes and phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes:

  • Promotes 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 calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes and phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes from the intestines
  • Stimulates osteoblasts Osteoblasts Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. Bones: Development and Ossification in bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types and enhances bone mineralization Bone mineralization Calcium (Ca2+) and phosphate (PO43–) combine to form hydroxyapatite crystals on the bone matrix. Bones: Development and Ossification
  • Is involved in:
    • Immune function and 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
    • 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 cholesterol metabolism Cholesterol Metabolism Cholesterol is an important lipid molecule that is used for many biologic functions. Cholesterol can either be synthesized from endogenous acetyl-CoA or absorbed from food in the GI tract. Because cholesterol is lipophilic, it must be transported through the bloodstream via lipoproteins, where it can be picked up by hepatocytes or peripheral tissues. Cholesterol Metabolism
    • Cell growth, proliferation, differentiation, and apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage

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), transport, and storage

Synthesis Synthesis Polymerase Chain Reaction (PCR) from sun exposure is very important for conversion into an active form.

  • In 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, UV light UV light That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-uv or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-uv or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. Bullous Pemphigoid and Pemphigus Vulgaris exposure causes a temperature-dependent rearrangement of 7-dehydrocholesterol, converting it into vitamin D3 ( cholecalciferol Cholecalciferol Derivative of 7-dehydroxycholesterol formed by ultraviolet rays breaking of the c9-c10 bond. It differs from ergocalciferol in having a single bond between C22 and C23 and lacking a methyl group at C24. Calcium Hemostasis and Bone Metabolism). 
  • Vitamin D3 is hydroxylated 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 to 25-hydroxyvitamin D3 (25(OH)D3):
    • Also known as calcidiol calcidiol The major circulating metabolite of vitamin d3. It is produced in the liver and is the best indicator of the body’s vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. Calcium Hemostasis and Bone Metabolism, calcifediol, and 25-hydroxycholecalciferol
    • 25(OH)D3 is the primary circulating form of vitamin D in the body and is what is measured clinically in lab work.
    • 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: 2–3 weeks 
  • 25(OH)D undergoes a second hydroxylation in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D3 (1,25(OH)D3):
    • Also known as calcitriol Calcitriol The physiologically active form of vitamin d. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. Parathyroid Glands: Anatomy 
    • Most active form
    • 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: 4–6 hours 
  • Vitamin D2 (ergocalciferol) is synthesized by fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology, undergoes two hydroxylations, and has biologic activity similar to 1,25(OH)D3.
  • Both vitamins D2 and D3 can be absorbed from the intestines:
    • Absorbed via simple 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 and membrane 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
    • Fat enhances 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
    • Vitamin D is incorporated into micelles Micelles Particles consisting of aggregates of molecules held loosely together by secondary bonds. The surface of micelles are usually comprised of amphiphatic compounds that are oriented in a way that minimizes the energy of interaction between the micelle and its environment. Liquids that contain large numbers of suspended micelles are referred to as emulsions. Malabsorption and Maldigestion, absorbed by enterocytes, and packaged into chylomicrons.
Vitamin d types

Types of vitamin D

Image by Lecturio. License: CC BY-NC-SA 4.0

Daily requirement

Guidelines vary around the world and for some professional societies. The U.S. RDAs are:

  • Infants: 400 IU (10 µg)
  • People 1–70 years of age, including pregnant/lactating women: 600 IU (15 µg)
  • People ≥ 71: 800 IU (20 µg)

Sources of vitamin D

  • The primary source of vitamin D is sunlight exposure:
    • 5–30 minutes of midday sun exposure to the face, arms, hands, and legs
    • Sunscreens block vitamin D–producing UV rays UV rays That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-uv or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-uv or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. Bullous Pemphigoid and Pemphigus Vulgaris, but many people do not apply sufficient amounts to block all vitamin D synthesis Synthesis Polymerase Chain Reaction (PCR).
  • Vitamin D is not found in breast milk. 
  • Few foods contain vitamin D; some that do include:
    • Fatty 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 (trout, salmon, tuna, and mackerel) 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 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 oils 
    • Mushrooms Mushrooms Mycology (vitamin D2)
  • Fortified dairy products provide most of the vitamin D in the American diet:
    • Milk and plant milk alternatives (e.g., soy, almond, or oat milk)
    • Orange juice 
    • Cereal 
    • Infant formula

Groups at risk for vitamin D deficiency

  • Diets low in vitamin D; these are more common in people who:
    • Have a milk allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction or lactose intolerance Lactose intolerance Lactose intolerance (LI) describes a constellation of symptoms due to lactase deficiency (LD), the enzyme located in the brush border of the absorptive cells in the small intestine. Lactose is the disaccharide present in milk and requires hydrolysis by lactase to break it down into its 2 absorbable constituents, glucose and galactose. Lactose intolerance typically presents with bloating, abdominal cramping, diarrhea, and flatulence. Lactose Intolerance
    • Consume restrictive diets (e.g., vegan)
  • Breastfed infants
  • Older adults: 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 does not synthesize vitamin D3 efficiently.
  • People with limited sun exposure 
  • Dark-skinned people: melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis in the epidermal layer of 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 results in a reduced ability to produce vitamin D from sunlight.
  • Conditions that cause fat malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity ( BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity ≥ 30): vitamin D is sequestered in the subcutaneous tissues, which ↓ circulating levels.
  • Chronic renal insufficiency: impaired hydroxylation in 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

Symptoms of deficiency

Modest and even severe vitamin D deficiency is widely prevalent around the world and sufficient intake is necessary for bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types and general health. With severe deficiency, the following may result:

  • Hypophosphatemia Hypophosphatemia A condition of an abnormally low level of phosphates in the blood. Bartter Syndrome, hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia, and secondary hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types demineralization
  • Rickets Rickets Disorders caused by interruption of bone mineralization manifesting as osteomalacia in adults and characteristic deformities in infancy and childhood due to disturbances in normal bone formation. The mineralization process may be interrupted by disruption of vitamin d; phosphorus; or calcium homeostasis, resulting from dietary deficiencies, or acquired, or inherited metabolic, or hormonal disturbances. Osteomalacia and Rickets in children; presents with:
    • Weak or soft bones 
    • Stunted growth 
    • Bowed legs and difficulty walking
    • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Osteomalacia Osteomalacia Disorder caused by an interruption of the mineralization of organic bone matrix leading to bone softening, bone pain, and weakness. It is the adult form of rickets resulting from disruption of vitamin d; phosphorus; or calcium homeostasis. Osteomalacia and Rickets in adults:
    • Presentation similar to that for rickets Rickets Disorders caused by interruption of bone mineralization manifesting as osteomalacia in adults and characteristic deformities in infancy and childhood due to disturbances in normal bone formation. The mineralization process may be interrupted by disruption of vitamin d; phosphorus; or calcium homeostasis, resulting from dietary deficiencies, or acquired, or inherited metabolic, or hormonal disturbances. Osteomalacia and Rickets in children
    • Increased risk of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures

Toxicity Toxicity Dosage Calculation

  • Hypervitaminosis D: causes increased 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 calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes in the GI tract, which may cause hypercalcemia Hypercalcemia Hypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Hypercalcemia, which can lead to:
    • 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
    • Muscle weakness
    • Neuropsychiatric disturbances
    • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
    • Dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration, polydipsia Polydipsia Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as diabetes mellitus; diabetes insipidus; and nephrogenic diabetes insipidus. The condition may be psychogenic in origin. Diabetes Insipidus, polyuria Polyuria Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. Renal Potassium Regulation, and 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
  • In extreme cases, vitamin D toxicity Vitamin D Toxicity Hypercalcemia causes:
    • Renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
    • Calcification of soft tissues throughout the body (including in coronary vessels and heart valves)
    • Cardiac arrhythmias

Vitamin E: Tocopherols

Vitamin E is a group of compounds that includes tocopherols and tocotrienols. Vitamin E is an important antioxidant that is synthesized only in plants Plants Cell Types: Eukaryotic versus Prokaryotic.

Forms

There are 8 chemical forms of tocopherol:

  • α-, β-, ɣ-, and Δ-tocopherol 
  • α-, β-, ɣ-, and Δ-tocotrienol
  • Only α-tocopherol has significant activity in humans.

Functions

Vitamin E is the fat-soluble equivalent of vitamin C Vitamin C A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. Water-soluble Vitamins and their Deficiencies (which is water-soluble) in that it acts as an antioxidant. Vitamin E is a free radical Free Radical Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Nitroimidazoles scavenger and can donate electrons and is involved in:

  • Fatty acid oxidation 
  • Cellular respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose and Nasal Cavity: Anatomy
  • Prolonging the life 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 by removing free radicals Free radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Ischemic Cell Damage
  • Protecting membrane lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids from peroxidation
  • Indirectly inhibiting arachidonic acid Arachidonic Acid An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. Nonsteroidal Antiinflammatory Drugs (NSAIDs) metabolism → inhibition of platelet aggregation Platelet aggregation The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin; collagen) and is part of the mechanism leading to the formation of a thrombus. Hemostasis
  • Inhibiting protein kinase Protein kinase A family of enzymes that catalyze the conversion of ATP and a protein to adp and a phosphoprotein. Interferons C, which is involved in cell proliferation and differentiation

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 and transport

  • Ingested in the diet, digested by 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, absorbed by intestinal mucosal cells, and packaged into chylomicrons
  • Chylomicrons transport the α-tocopherol form of vitamin E 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 through the lymphatic system Lymphatic system A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs.
  • In hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy, α-tocopherol is packaged in VLDLs and secreted into the bloodstream.

Daily requirement

The RDAs for vitamin E are:

  • Infants and children: requirements increase from 4 mg at birth to 7 mg by age 8
  • Children 9–13: 11 mg
  • People ≥ 14, including pregnant women: 15 mg daily
  • Lactating women: 19 mg

Dietary sources

  • Wheat germ
  • Nuts and seeds (especially almonds, peanuts, and peanut butter)
  • Plant oils:
    • Olive oil
    • Sunflower oil
    • Safflower oil
  • Fortified cereals

Deficiency

  • Very rare in humans
  • May 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:
    • Fat malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion
    • Rare genetic disorder called “ 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 and vitamin E deficiency” (AVED) 
  • Clinical manifestations:
    • Neuromuscular signs of 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 and peripheral neuropathy Neuropathy Leprosy
    • Hemolytic 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

  • Supplementation is indicated in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with vitamin E deficiency.
  • Vitamin E supplements have been studied in many diseases and are not currently recommended as treatment or prevention for any condition other than vitamin E deficiency.

Toxicity Toxicity Dosage Calculation

  • Increased risk of hemorrhagic stroke Hemorrhagic stroke Stroke due to rupture of a weakened blood vessel in the brain (e.g., cerebral hemispheres; cerebellum; subarachnoid space). Subarachnoid Hemorrhage due to vitamin E’s ability to inhibit platelet aggregation Platelet aggregation The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin; collagen) and is part of the mechanism leading to the formation of a thrombus. Hemostasis and antagonize vitamin K–dependent clotting factors
  • Increased risk of prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer in men
  • Small increased risk of all-cause mortality Mortality All deaths reported in a given population. Measures of Health Status

Vitamin K: Quinone

Vitamin K is consumed in the diet and synthesized by the normal intestinal flora. Newborns cannot produce vitamin K because they have a sterile Sterile Basic Procedures gut.

Forms

  • Vitamin K1: phylloquinone, primary dietary form
  • Vitamin K2: menaquinone, primarily from bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology, including bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology within the human GI tract

Functions

  • Vitamin K is an active coenzyme for glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids carboxylase, which carboxylates important factors involved in coagulation:
    • Procoagulants factors II, VII, IX, and X; after carboxylation, these 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 gain an affinity for platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology and promote blood clotting.
    • Anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants: proteins C Proteins C Protein C cleaves and inactivates factors V and VIII. Hemostasis and S
  • Vitamin K is also important as a cofactor for multiple 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 involved in bone mineralization Bone mineralization Calcium (Ca2+) and phosphate (PO43–) combine to form hydroxyapatite crystals on the bone matrix. Bones: Development and Ossification.

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 and transport

  • Ingested in the diet, digested by 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, absorbed by intestinal mucosal cells, and packaged into chylomicrons
  • Repackaged in the hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy into VLDLs for secretion Secretion Coagulation Studies into the blood
  • Rapidly metabolized and excreted (very little vitamin K circulates in the blood)

Daily requirements

The RDAs for vitamin K are:

  • Infants: 2–2.5 µg/day 
  • Children 1–3 years old: 30 µg
  • Children 4–13 years old: 55–60 µg 
  • Adolescents 14–18 years old: 75 µg/day
  • Adult women (including 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): 90 µg/day
  • Adult men: 120 µg/day

Dietary sources

  • Found mostly in green, leafy vegetables:
    • Collard and turnip greens
    • Spinach
    • Kale
    • Broccoli
  • Other dietary sources with lower amounts include:
    • Soybeans and soybean oil
    • Blueberries
    • Chicken

Deficiency

Vitamin K deficiency is extremely rare, but because it blocks the protein carboxylation essential for blood clotting, a severe deficiency can result in bleeding problems. 

  • Clinical bleeding symptoms due to vitamin K deficiency:
  • Diagnosis: 
    • Lab testing of the PT and INR is done in suspected deficiency.
    • These same tests are used to monitor anticoagulation Anticoagulation Pulmonary Hypertension Drugs status with the anticoagulant medication warfarin Warfarin An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. Anticoagulants.
  • Chronic deficiency can also lead to reduced bone mineralization Bone mineralization Calcium (Ca2+) and phosphate (PO43–) combine to form hydroxyapatite crystals on the bone matrix. Bones: Development and Ossification.
  • Deficiencies are more common in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
    • With fat malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion
    • On longer courses of antibiotics, which affects the intestinal bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology

Therapeutic uses and clinical relevance

  • Newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn infants should receive an IM injection of vitamin K at birth to prevent bleeding (vitamin K transport across the placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity is poor).
  • Supplementation of vitamin K is essential in 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).
  • Vitamin K in the diet (such as eating greens or in a supplement) interferes with the anticoagulation Anticoagulation Pulmonary Hypertension Drugs medication warfarin Warfarin An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. Anticoagulants ( Coumadin Coumadin An anticoagulant that acts by inhibiting the synthesis of vitamin k-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. Anticoagulants), which is a vitamin K antagonist. 
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship taking warfarin Warfarin An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. Anticoagulants for anticoagulation Anticoagulation Pulmonary Hypertension Drugs need to maintain a stable dietary intake and avoid large daily variations of greens.
    • Vitamin K is the antidote Antidote An antidote is a substance that counteracts poisoning or toxicity. Substances that can cause poisoning include heavy metals (from occupation, treatments, or diet), alcohols, environmental toxins, and medications. Antidotes of Common Poisonings to excess anticoagulation Anticoagulation Pulmonary Hypertension Drugs.
  • Used to reverse poisoning by rodenticides, which contain high doses of coumarin

Toxicity Toxicity Dosage Calculation

  • The U.S. Food and Nutrition Board (FNB) at the National Academy of Medicine has not established safe upper limits for vitamin K.
  • The FNB states, “No adverse effects associated with vitamin K consumption from food or supplements have been reported in humans or animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic.”
  • A synthetic, water-soluble form of vitamin K, known as menadione, was previously used in premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis infants and was associated with hemolytic 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 and jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice. This formulation is no longer available.

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References

  1. Pazirandeh, S., Burns, D.L. (2020). Overview of vitamin A. UpToDate. Retrieved June 3, 2021, from https://www.uptodate.com/contents/overview-of-vitamin-a
  2. National Institutes of Health Office of Dietary Supplements. (2021). Vitamin A Fact Sheet for Health Professionals. Retrieved June 3, 2021, from https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/ 
  3. Pazirandeh, S., Burns, D.L. (2020). Overview of vitamin D. UpToDate. Retrieved June 3, 2021, from https://www.uptodate.com/contents/overview-of-vitamin-d 
  4. National Institutes of Health Office of Dietary Supplements. (2021). Vitamin D Fact Sheet for Health Professionals. Retrieved June 3, 2021, from https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/ 
  5. Pazirandeh, S., Burns, D.L. (2020). Overview of vitamin E. UpToDate. Retrieved June 3, 2021, from https://www.uptodate.com/contents/overview-of-vitamin-e
  6. National Institutes of Health Office of Dietary Supplements. (2021). Vitamin E Fact Sheet for Health Professionals. Retrieved June 3, 2021, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/ 
  7. Pazirandeh, S., Burns, D.L. (2020). Overview of vitamin K. UpToDate. Retrieved June 3, 2021, from https://www.uptodate.com/contents/overview-of-vitamin-k
  8. National Institutes of Health Office of Dietary Supplements. (2021). Vitamin K Fact Sheet for Health Professionals. Retrieved June 3, 2021, from https://ods.od.nih.gov/factsheets/vitaminK-HealthProfessional/ 

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