Lecture 9 Vitamins Jan 2023 PDF

Lecture 9. Vitamins Peter Meyer MD, Ph.D.  LEARNING OBJECTIVES Describe vitamins in general Know each water soluble vitamin, their roles at cellular levels; the deficiency disorders associated with each vitamin; symptoms of these disorders Know the different...

Lecture 9. Vitamins Peter Meyer MD, Ph.D.  LEARNING OBJECTIVES Describe vitamins in general Know each water soluble vitamin, their roles at cellular levels; the deficiency disorders associated with each vitamin; symptoms of these disorders Know the different fat soluble vitamins, their absorption mechanism, storage forms in the body, cellular functions, deficiency disorders, and toxicity issues. Describe the role of vitamins as coenzymes in promoting enzyme activity Vitamins – An Overview Vitamins are chemically unrelated, essential organic compounds that cannot be synthesized in adequate amounts by the human body. Vitamins differ from macronutrients (proteins, carbohydrates and fat) with regards to: – Structure: They are Individual units (not linked together or polymers). – Function: They do not yield energy (many are coenzymes that assist enzymes). – Amount found in food: They are present in small quantities. Vitamins – An Overview (vitamin B9) Cobalamin (vitamin B12) Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry Absorption: – Water soluble (B Vitamins & Vitamin C) absorbed directly into blood – Fat-soluble (Vitamins A, E, D, and K) enter lymph and then blood Storage: – Fat soluble are often stored; Unnecessary supplementation may lead to toxicity – Water soluble are rarely stored Water Soluble Vitamins: B Vitamins and Vitamin C  Sources of B Vitamins High amounts in meat and seafood, particularly concentrated in turkey, tuna and liver. Good sources include legumes (beans), whole grains, potatoes, bananas, chili peppers, tempeh (soy), nutritional yeast, brewer's yeast, and molasses. Low quantities in whole unprocessed carbohydrate based foods. B vitamins thiamine, riboflavin, niacin, and folic acid are added back to white flour after processing. This is sometimes called "Enriched Flour“. https://www.centurypa.com/blog/post/vitamin-b-benefits Thiamine (B1) Part of the coenzyme thiamine pyrophosphate (TPP) Major role as coenzyme in glucose metabolism Facilitates – Decarboxylation reactions – Transferase reactions – Synthesis of acetylcholine and GABA https://www.easynotecards.com/uploads/689/65/3386f18_13cabf87a7b__8000_00001284.jpg  Examples of Thiamine Pyrophosphate (TPP)-Dependent Reactions Decarboxylation reactions are required for energy metabolism and production of ATP which are particularly important for the nervous system, the heart, and skeletal muscle. Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry  Thiamine Deficiency Malnourished and chronic alcoholics. – Prolonged cooking destroys thiamine. – Ethanol inhibits absorption of thiamine and TPP formation. Thiamine deficiency: Beriberi “extreme weakness” – Wet – Affects cardiovascular system. Heart failure and edema. – Dry – Affects nervous system. Wasting and partial paralysis from damaged peripheral nerves. http://www.daviddarling.info/encyclopedia/B/beriberi.html Thiamine Deficiency: Wernicke-Korsakoff Syndrome Form of dry beriberi Acute phase: Wernicke’s encephalopathy – Ocular disturbances (e.g. nystagmus, a rhythmic to-and-fro motion of the eye balls) – Changes in mental state (confusion) – Unsteady stance and gait (ataxia) – A medical emergency. Left untreated it can lead to coma and death. Treatment: Prompt administration of thiamine (and other vitamins and minerals) then glucose Chronic phase: Korsakoff’s syndrome: Severe memory impairment without dysfunction in intellectual abilities – Amnesia – Confabulation, making things up Mnemonic: Thiamine deficiency – Tall Tales Riboflavin (B2) Part of coenzymes for reduction/oxidation (redox) reactions in energy metabolism – Flavin mononucleotide (FMN) – Flavin adenine dinucleotide (FAD) Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)/16%3A_Oxidation_and_reduction_reactions/16.05%3A_Hydrogenation_of_alkenes_and_dehydrogenation_of_alkanes  Riboflavin Deficiency Destruction of riboflavin – Ultraviolet light and irradiation (put milk in opaque containers) – Not destroyed by cooking Riboflavin Deficiency is not associated with a major human disease, but it frequently https://www.flickr.com/photos/dokidok/2369779994 https://www.wisegeek.com/what-is-riboflavin.htm#close- accompanies other vitamin deficiencies view-of-reddened-blue-eye Deficiency – Oral: Angular cheilitis, glossitis – Ocular: Photophobia, itching and burning eyes – Genital: Scrotal dermatitis Mnemonics: Riboflavin: flavin mononucleotide, FMN, and flavin adenine dinucleotide, FAD. Riboflavin deficiency: Redness  Niacin (B3) Two chemical structures – Nicotinic acid (not related to nicotine) – Nicotinamide: Major form of niacin in blood https://examine.com/supplements/vitamin-b3/#sources-and-composition_sources-and-structure Component of: – Nicotinamide adenine dinucleotide (NAD+) – Nicotinamide adenine dinucleotide phosphate (NADP+) NAD and NADP are coenzymes for many metabolic redox reactions – NAD+ ==> NADH – NADP+ ==> NADPH https://cnx.org/resources/b17e8c463121bd0cc2c0f273aa9a0b2b743f7aba/Figure_07_01_01ab.jpg NADH and FADH2 are high-energy compounds that convert their energy into ATP in the electron transport chain, so-called oxidative phosphorylation Sources of Niacin Present in: – Unrefined and enriched grains and cereal – Milk – Lean meats, particularly liver Can be synthesized from tryptophan (after protein synthesis has been met) Corn is low in both niacin and tryptophan and corn-based diets can cause niacin deficiency (pellagra)  Niacin-Deficiency Pellagra (the 4Ds): – Diarrhea – Dermatitis: peeling, redness, scaling, and thickening of sun-exposed areas. – Dementia – Death Primary: Dietary insufficiency Secondary: Poor ability to use niacin in the diet. Due to alcoholism, chronic diarrhea, Hartnup’s disease (inability to absorb nonpolar amino acids), and various medications https://www.netterimages.com/vitamin-b1-deficiency-pellagra-labeled-young-endocrinology-frank-h-netter-58182.html  Niacin-Therapeutic Uses Niacin deficiency Treatment of hyperlipidemia – High concentrations of niacin strongly inhibits lipolysis in adipose tissue. Therefore there is a decrease in free fatty acids in the blood and reduced synthesis of very-low-density lipoprotein (VLDL) in the liver and reduced levels of VLDL and LDL in the blood Side-effect: Niacin Flush – Itchy tingly sensation – Can be painful http://healthnewsreport.blogspot.com/2010/07/niacin-good-flushing-bad.html  Pantothenic Acid (B5) Part of chemical structure of Coenzyme A (CoA) CoA is important for the transfer of acyl (fatty) groups, e.g. – Fatty acyl CoA – Acetyl CoA – Succinyl CoA Deficiency and toxicity are rare Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry Deficiency of which vitamin causes the symptoms seen in these images? A. B1 (thiamine) B. B2 (riboflavin) C. B3 (niacin) D. B5 (pantothenic acid) The absorption of which vitamin is affected by alcohol consumption? A. B1 (thiamine) B. B2 (riboflavin) C. B3 (niacin) D. B5 (pantothenic acid) Pyridoxine (B6) Three forms: Pyridoxal, pyridoxine, and pyridoxamine Converted to active coenzyme pyridoxal phosphate Pyridoxal phosphate helps in: – Amino acid metabolism: Transamination and deamination reactions – Conversion of tryptophan to niacin or serotonin – Glycogen metabolism – Synthesis of heme and lipids Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry  Pyridoxine (B6) Commonly found in food (fruits, vegetables, and grain) Deficiency – Dietary deficiency rare – Isoniazid (a tuberculosis medication) can deplete pyridoxine levels (causes an inactive derivative with pyridoxal phosphate) – Causes depression, irritability, confusion, distal limb numbness Toxicity – Only water-soluble vitamin with significant toxicity – Occurs at intake > 200 mg/day or > 100 times the recommended daily amount – Irreversible nerve degeneration: Destruction of dorsal root ganglia leading to peripheral sensory neuropathy Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry Biotin (B7) Coenzyme that carries activated carbon dioxide Facilitates carboxylation reactions: – Participates in gluconeogenesis and fatty acid synthesis Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry  Biotin Deficiencies FYI – Rare, widely distributed in food and intestinal bacteria can make biotin. – Deficiency can occur if 2 raw egg whites are consumed daily for several months. Avidin present in raw egg white binds strongly to biotin and prevents its absorption. – Deficiency symptoms include dermatitis, glossitis, loss of appetite and nausea. FYI: The strong interaction between avidin and biotin is extensively used in research, diagnostics biotin and avidin - Bing images and medical devices  Folate/Folic Acid (B9) Active forms include dihydrofolate and tetrahydrofolate Transfers single-carbon compounds during metabolism – Converts vitamin B12 to its active coenzyme form – Helps in DNA synthesis and repair – Aids in rapid cell division and growth https://www.chem.uwec.edu/Webpapers2001/okonekjj/Pages/Introduction/intropage.html  Folate Deficiency Sources: Fortified grain products Deficiency The most common vitamin deficiency in the U.S., particularly among pregnant women and alcoholics Megaloblastic/macrocytic anemia (anemia with presence of larger than normal red blood cells) caused by decreased synthesis of purines and TMP and inability of cells to synthesize DNA and to divide – Importantly, can also be caused by vitamin B12 deficiency Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry MCV = Mean corpuscula volume or mean size of red blood cells Folate Deficiency Neural tube defects: spina bifida with incomplete closing of the backbone and membranes around the spinal cord Affect 4,000 pregnancies per year in the US Folate supplementation is recommended before and during pregnancy (first trimester) Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry Folate Inhibitors: Antibiotics and Antiproliferative Agents Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry The antibiotic trimethoprim inhibits bacterial dihydrofolate reductase with 1000 fold greater affinity than the human enzyme Sulfa and trimethoprim are antibiotics Methotrexate is an antiproliferative agent Cobalamin (B12) Cobalt-containing ring system related to porphyrin (in hemoglobin) Also contains cyanide! In the coenzyme forms the cyanide is replaced to form 5’-deoxyadenosyl cobalamin or methylcobalamin Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry Cobalamin (B12) Functions Required for two types of reactions A. Remethylation of homocysteine to methionine B. Degradation of some amino acids and fatty acids with odd numbers of carbon Deficiency results in accumulation of unusual fatty acids that become incorporated into cell membranes Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry  Cobalamin (B12) Intake and Absorption Only synthesized by microorganisms and present exclusively in animal based-foods Requires digestion and absorption 1. Gastric acid releases cobalamin from protein in food 2. The parietal cells in the stomach produce intrinsic factor 3. Intrinsic factor binds to cobalamin and helps absorb the cobalamin in the small intestine (ileum) Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry  Cobalamin (B12) Deficiency Cobalamin deficiency can be caused by: – Low intake: due to vegan diets or malnutrition. – Lack of hydrochloric acid or intrinsic factor: due to for example antacids such as proton pump inhibitors, partial or total gastrectomy, or excessive alcohol intake resulting in atrophic gastritis. – Failure to absorb the vitamin: (e.g. inflammatory bowel disease or celiac disease). In contrast to other water-soluble vitamins, several years worth of cobalamin are stored in the body.  Cobalamin (B12) Deficiency -Manifestations The folate trap Lack of cobalamin results in entrapment of folate as 5- methyl tetrahydrofolate (folate trap) and deficiency in other forms of tetrahydrofolate. Effects of cobalamin deficiency mimic those of folate deficiency resulting in pernicious anemia (macrocytic anemia). Can also cause neuropsychiatric symptoms (due to X X incorporation of odd-chain fatty acid metabolites into cell membranes). Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry Vitamin C (Ascorbic Acid) Coenzyme in collagen formation – Matrix for connective tissue, bone, and tooth formation Coenzyme in other reactions – Conversion of tryptophan to serotonin – Conversion of tyrosine to norepinephrine https://en.wikipedia.org/wiki/Vitamin_C  Vitamin C (Ascorbic Acid) Antioxidant (along with vitamins E and A) – Defends against free radicals – Protects tissues from oxidative stress Disease prevention Diets rich in antioxidants reduce risk of chronic diseases such as heart disease and certain cancers Supplementation with vitamins A, C, and E have failed to show convincing benefits Prevention and treatment of common cold – Conflicting and controversial research – Deactivates histamine Vitamin C – Deficiency Leads to Scurvy Signs of deficiency – Gums bleed easily around teeth – Loose teeth – Fragile blood vessels: Capillaries under skin break spontaneously https://en.wikipedia.org/wiki/Vitamin_C  The inability to make enough HCl in the stomach would greatly affect the dietary uptake of which vitamin? A. B1 (thiamine) B. B3 (niacin) C. B5 (pantothenic acid) D. B9 (Folic acid) E. B12 (Cobalamin) A patient comes in because he’s tired and pale. Tests show anemia and larger than normal red blood cells (macrocytic anemia). This could be caused by deficiency of which two B vitamins? A. B1 (thiamine) or B3 (niacin) B. B1 (thiamine) or B9 (folic acid) C. B5 (pantothenic acid) or B12 (cobalamin) D. B3 (niacin) or B9 (folic acid) E. B9 (folic acid) or B12 (cobalamin) The ingestion of raw egg whites can reduce the uptake of which B vitamin? A. B1 (thiamine) B. B5 (pantothenic acid) C. B7 (biotin) D. B9 (folic acid) E. B12 (cobalamin) Fat-Soluble Vitamins  Fat-Soluble Vitamins Differ from water-soluble vitamins Require bile for digestion & absorption Travel through lymphatic system Many require transport proteins in bloodstream Excess amount consumed are stored – Liver and adipose tissue Risk of toxicity is greater  Vitamin A First fat-soluble vitamin recognized Three different forms (retinoids) – Retinol (alcohol), retinal (aldehyde), and retinoic acid – Precursor is beta carotene Important for vision, reproduction, growth, and maintenance of epithelial tissues https://oneclass.com/class-notes/ca/uottawa/hss/hss2342/1934363-hss2342-lecture-12.en.html  Conversion of Vitamin A Compounds https://oneclass.com/class-notes/ca/uottawa/hss/hss2342/1934363-hss2342-lecture-12.en.html Retinol and retinal can be interconverted and can form retinoic acid Retinoic acid, in contrast, cannot be converted to the other vitamin A compounds  Which Vitamin A does What? https://oneclass.com/class-notes/ca/uottawa/hss/hss2342/1934363-hss2342-lecture-12.en.html Retinal, an aldehyde: RETINA, vision Retinoic acid: Weak acids used for skin care, so maintenance of epithelial tissues Retinol, an alcohol: Too much alcohol can lead to what? Reproduction  Absorption and Transport of Vitamin A FYI 4 6 1. Absorbed along with dietary fats 2. Packed into chylomicrons (lipoproteins) 5 3. Enters blood via the lymphatic system 4. Excess amounts are stored in the liver (1-2 years) 5. Transport of retinol to extrahepatic tissues via blood requires a transport protein retinol binding protein (RBP) 5 3 6. RBP binds to cells that have an RBP-receptor and vitamin A is transported by the RBP-receptor into 6 the cell. 2 1 Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry Vitamin A (Retinal) Vision – Cornea: Helps maintain healthy, transparent surface for crystal clear visions – Retina: Involved in the retinal cycle; component of the photopigment rhodopsin present in photoreceptor cells (rods) http://www.chm.bris.ac.uk/motm/retinal/retinalh.htm  Vitamin A (Retinoic Acid) Retinoic Acid, the acid form of vitamin A, binds to its receptor inside target cells. The retinoic acid/receptor complex binds specific enhancers to initiate expression of retinoic acid-responsive genes. These genes affect protein synthesis and cell differentiation in epithelial cells. In the skin, retinoic acid supports normal differentiation of epithelial tissues. In mucous membranes retinoic acid helps maintain structural integrity. https://hopes.stanford.edu/wp-content/uploads/2011/08/retinoic-acid.jpg Vitamin A (Retinol) Transport form of Vitamin A in blood Affects – Sperm development – Normal fetal development – Growth of children – Bone remodeling  Deficiency of Vitamin A Vitamin A is found in a variety of foods: – Liver, kidney, cream, and egg yolk – Yellow, orange, and dark green vegetables and fruits Vitamin A deficiency can cause: – Night blindness due to inadequate supply of retinal to retina (back of the eye) – Pathologic dryness of the cornea and conjunctiva (xerophthalmia) which can lead to ulceration, scarring and loss of vision. Vitamin A deficiency is the leading cause of blindness world-wide! https://en.wikipedia.org/wiki/Nyctalopia#/media/File:P360_Onderdendam_goed_nachtzicht_ns_nachtblind.jpg Clinical Indications for Vitamin A Retinol and its precursors are used as dietary supplements Retinoic acid is useful in dermatology A specific form (all-trans retinoic acid) is used as treatment of promyelocytic leukemia Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry Vitamin A Toxicity Hypervitaminosis A Occurs when the maximum liver storage is exceeded Excess vitamin A causes systemic toxicity May occur with intake > 7.5 mg/day; the recommended intake is 3 mg/day or 10,000 IU, so vitamin A has a narrow therapeutic index Usually occurs with excessive vitamin supplementation Symptoms: – Skin: Dry and itchy – Liver: Enlarged may become damaged and cirrhotic – Central nervous system: Increase in intracranial pressure mimicking a tumor – Bone: Reduced mineral bone density and possibly osteoporosis Pregnant women should not ingest excessive vitamin A because it may cause fetal malformations  Intake of Beta-Carotene Is Safe Beta-carotene (precursor of vitamin A) is found in many yellow, orange, and green fruits and vegetables Excessive intake does not cause toxicity, the body only cleaves beta carotene when it needs vitamin A Symptom: Yellow skin (not harmful) https://www.jaad.org/article/S0190-9622(12)00248-4/pdf  Which form of vitamin A is component of rhodopsin? A. Retinal B. Retinol C. Retinoic acid D. Beta carotene Animal-consumed vitamin A precursors are converted to which form? A. Retinol B. Retinal C. Retinoic Acid D. Retinel E. Retinil Which form of vitamin A is used to treat acne and other skin disorders? A. Retinal B. Retinol C. Retinoic acid D. Beta carotene E. Retinel  Vitamin D Vitamin D is not an essential nutrient since the body can synthesizes it from a derivative of cholesterol (7-DHC) and sunshine. Five to 10 min exposure to summer sun 2-3 times a week is sufficient to get enough vitamin D. This depends on skin color, latitude, season, and time of day. There is no risk of toxicity since sunlight can degrade the vit. D precursor with prolonged exposure. Vitamin D has to be activated through two hydroxylation reactions, one in the liver on carbon 25 produces 25-hydroxyvitamin D3, or calcidiol, and a second one in the kidneys on carbon 1 produces 1,25-dihydroxyvitamin D3, or https://www.precisionnutrition.com/genetics-vitamin-d calcitriol, the active form of vitamin D. Patients with impaired liver or kidney function should be prescribed calcitriol, the active form of vitamin D, since they may not be able to activate vitamin D.  Vitamin D Functions Active form of vitamin D is a hormone Helps to maintain adequate plasma calcium levels Works with parathyroid hormone (PTH) Target organs: – Intestine: Increased calcium absorption – Kidney: Increased calcium reabsorption, decreased calcium excretion – Bones: Stimulating resorption of bone to release calcium when necessary To support strong bones, always prescribe vitamin D with calcium. In the absence of sufficient calcium levels, vitamin D and PTH can cause excessive bone resorption and weakened bones, or osteoporosis. Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry Vitamin D Deficiency Intake of vitamin D: – Daily recommended intake of vitamin D is 200-600 IU – Present in fatty fish, liver and egg yolk – Synthesized by the body by exposure to sun light Vitamin D deficiency is very common – Contributory factors Dark skin, lack of sunlight – Triggers net demineralization of bone due to secondary hyperparathyroidism – Vitamin D deficiency is also linked to autoimmune conditions and impaired immune function. Vitamin D deficiency is very common. Check vitamin D levels in all patients! Deficiency can cause osteoporosis and increased risk of various immune disorders.  Rickets Osteomalacia – Affects children – Affects adults – Bones fail to calcify normally so they bend – Poor mineralization of bones – Bones are soft, flexible, brittle, and deformed https://www.dreamresearchgroup.com/2014/10/rickets-affects- development-of-bones.html https://www.sciencephoto.com/media/262326/view/rickets- vitamin-d-deficiency-in-man Vitamin D Toxicity Vitamin D has a wide therapeutic window and is safe to take as a supplement. Extremely high doses, 100,000 IU/day for weeks or months, or more than 100 times the recommended dose, can cause: Loss of appetite Nausea Increased thirst Stupor (reduced consciousness) Raised plasma calcium concentrations Calcium depositions in many organs Vitamin D is very safe. Everyone can take 3,000 to 5,000 IU per day as a supplement.  Vitamin E FYI There are four different forms of vitamin E, or tocopherol, alpha, beta, gamma, and delta. Alpha-tocopherol has the highest vitamin E activity in the body. https://www.vita-dose.com/structure-of-vitamin-e.html  Vitamin E: Functions FYI Vitamin E is an antioxidant that stops chain reactions of free radical-mediated damage. Vitamin E inserts itself into the lipid bilayer of plasma membranes where it protects unsaturated fatty acids from oxidative damage. Vitamin E is cardioprotective. It prevents the oxidation of LDL cholesterol and thereby reduces inflammation and atherosclerosis. Vitamin E Requirement and Deficiency Recommended intake: – 15 mg, higher amounts are needed with FYI higher intake of polyunsaturated fatty acids – High amounts in vegetable oils – Moderate amounts in liver and eggs Primary deficiency is rare; occurs in premature infants Secondary deficiency occurs due to fat hemolytic anemia - Bing images malabsorption Effects of deficiency – Abnormal cellular membranes causing Red blood cell fragility resulting in hemolytic anemia Vitamin E Clinical Use and Toxicity Clinical use: – Populations consuming diets rich in fruits and vegetables show decreased incidence of some chronic diseases – However, clinical trials have failed to show benefits from supplementation of vitamins A, C, or E; multivitamins with folic acid, or antioxidant combinations for prevention of cardiovascular disease or cancer – In fact, high doses of vitamin E may increase the risk of stroke Toxicity: – The least toxic of the fat soluble vitamins – No toxicity with doses of 300 mg/day (20 times the recommended intake) Liver regulates vitamin E concentrations Vitamin K FYI Several forms: – Phylloquinone (in plants) – Menaquinone (intestinal bacterial flora) – Menadione (synthetic form) Main function: Post-translational modification of certain coagulation factors It is also needed for the metabolism of a bone protein (osteocalcin)  Role of Vitamin K in Blood Coagulation Vitamin K: Coenzyme of gamma glutamyl carboxylase (GGC) GGC catalyzes carboxylation of glutamic acid residues in factors II, VII, IX, X (and protein C) enabling them to bind to activated platelet surfaces (via Ca2+) Ferrier, D. R. Lippincott’s illustrated reviews Biochemistry  Warfarin Is a Vitamin K Antagonist Warfarin inhibits the action of vitamin K epoxide reductase (VKOR) Affects conversion of vitamin K epoxide (inactive) to vitamin K (active) Leads to gradual depletion of active vitamin K levels Functional impairment of many clotting factors: II, VII, IX, X Used for: – Prevention of embolic events in patients with AFib – Prevention and treatment of venous thromboembolic events Takes a few days to take effect Heparin/LMWH are used for immediate anticoagulant effect while warfarin takes effect Patients on warfarin have to regularly check coagulation https://www.researchgate.net/figure/In-the-vitamin-K-cycle-vitamin-K-dependent-gamma-carboxyglutamic-acid-Gla-proteins- are_fig1_276159848 parameters (INR, international normalized ratio) since many drugs and vitamin-K containing foods affect its efficacy FYI: Rodenticides (rat poisons) contain warfarin  Vitamin K: Requirements, Deficiency, and Toxicity Requirements: (90-120 micrograms/day) – Vitamin K is found in cabbage, kale, spinach, egg yolk, and liver. – Also extensively synthesized in the gut. Deficiency: – Primary deficiency is rare, except in newborns who have sterile intestines and are given one intramuscular dose of vitamin K. – Secondary deficiency: Decreased gut flora, e.g. due to antibiotics Drugs like Warfarin Toxicity – Prolonged administration of large doses of synthetic vitamin K can lead to hemolytic anemia and jaundice in infants (due to toxic effects on red blood cell membranes). Which two organs are needed for the activation of vitamin D? A. Lungs and kidneys B. Lungs and liver C. Intestines and kidneys D. Liver and kidneys E. Intestines and lungs Vitamin D along with which other hormone raises plasma calcium levels? A. Insulin B. Human growth hormone C. Parathyroid hormone D. Cortisol E. Thyroid hormones  Which three vitamins are considered antioxidants? A. A, C, E B. A, D, E C. A, E, K D. C, D, E E. C, E, K Vitamins Summary