vitamins and vitamin E
thiamin DRI
1.2mg/day for men -1.1mg/day for women
vitamin E DRI
15mg/day as alpha tocopherol -increased requirement w/ PUFA intake ---vit c and Se may spare vit E
thiamin function
CHO metab (Krebs) and serves as coenzyme in decarboxylation of: ---alpha-ketoglutarate to succinyl CoA ---Pyruvate to acetyl CoA -BCAA metab -synthesis of pentose and NADPH -membrane and nerve conduction
vitamin A delivery
delivery to target tissue is dependent on the synthesis of Retinol Binding Protein (RBP) --each mole of retinol combines w/ 1 mole of RBP to form holo-RBP --in plasma, holo-RBP interacts w/ transthyretin (TTR--formally known as prealbumin) -RBP-TTR complex is circulating form in plasma, from which retinol will be delivered into a target tissue ---Apo-RBP and TTR will be released
primary vitamin K deficiency
due to insufficient intake usually not seen in normal conditions
infantile beriberi
during first 2-4 months -in infants breast-fed by thiamine deficient mothers
B vitamins
Thiamin (B1) Riboflavin (B2) Niacin (B3) Adenine (B4) Panthotenic acid (B5) Pyridoxine (B6) Biotin (B7) Inositol (B8) Folate (B9) Para-aminobenzoic acid (PABA-B10) Folic Acid (B11, new name for folate) Cobalamin (B12)
cerebral beriberi
Wernicke Korsakoff syndrome in chronic alcoholics -first stage: Korsakoff psychosis. Mental confusion, inability to speak, dementia -second and last stage: Wernicke's encephalopathy. Ophtalmoplegia (eye nerve paralysis), nystagmus (eye rolling). Ataxia, coma, death ----this stage is medical emergency
breath pentane measurement
functional test -pentane is a product of linoleic and linolenic acids peroxidation and is exhaled through the lungs ---when vit E is low, pentane exhalation is high
erythrocyte hemolysis
functional test -shorter life of RBC in vit E deficiency ---lacks specificity
criteria of vitamins
group of organic compounds that are micronutrients, not macro -present as natural components in small amounts of food -not synthesized by the host in the amounts to meet normal physiological processes -essential for normal physiological functions -absence/deficiency or underutilization cause specific deficiency syndrome
tocopherol
have saturated side chain -alpha and beta tocopherol have highest bioactivity
tocotrienol
have unsaturated side chain -much lower bioactivity
vitamin A toxicity
amounts greater than 10x RDA -anorexia, dry, itchy skin, alopecia, ataxia, liver and spleen problems -beta-carotene ingestion does not pose serious side effects except yellow discoloration of the skin
four vital amines
antiberiberi, antiscurvy, antirickets, and antipellagra
secondary deficiency and newborns
hemorrhagic disease of newborn due to: -lipids and fat soluble vit poorly transferred through placenta -liver synthesis of blood clotting factors starts after several months -human milk is sterile and not good source of vit K -infant gut is sterile
thiamin deficiency
high risk groups include alcoholics, elderly, pts w/ TPN, raw-fish consumers, refined rice consumes -symptoms of depression, weakness, loss of appetite/weight, followed by cardiovascular and neurological symptoms
synthesis of pentoses and NADPH (thiamin)
in hexose monophosphate shunt --pathway in which sugars of various lengths are interconverted and pentoses are generated for nucleic acids syntheses
secondary vitamin K deficiency
induced by some disease or drug therapy --malabsorption of fat including biliary obstruction or steatorrhea -liver disease to the inability to use it for synthesis of coagulation factors -drugs: antibiotics as they wipe of intestinal flora, anticoagulants like warfarin, heparin. These are blood thinners -megadoses of vit A or E
vitamin A and cancer/heart disease risk
inverse relationship bw the level of consumption of provitamins A in fruits and veg and CVD, cancer and stroke -cancer patient tend to have low serum levels of beta-carotene
phylloquinone (K1)
isolated from plants (dark-green leafy veggies, the greener the better soruce) -tobacco has highest amount per unit weight and when its smoked a small amount of vit K is volatilized and absorbed -contain functional naphthoquinone ring and aliphatic side chain -contain phytyl side chain
bitot's spots
keratinization of cornea -localized spots
vitamin E functions continued
protective effects in atherogenesis (besides prevention of lipid oxidation) --inhibits platelet and other monocyte adhesions and aggregation -maintenance of normal reproductive systems -may be anticarcenogenic
anticoagulant factors
proteins C, S, Z -protein C=serves as brake on the speed of the intrinsic cascade, as feedback loop -Protein S=enhances the activity of protein C -Protein Z fxn is unknown
vitamin K toxicity
rare, might occur in infants when supplemented w/ menadione -results in hyperbilirubinemia and jaundice
vitamin A
refers to group of metabolites --retinoids active vitamins -carotenoids==provitamins A
vitamin K functions
regulates the synthesis of clotting proteins -procoagulant factors and anticoagulant factors -all factors and proteins in blood clotting are synthesized in liver by carboxylation and contain gamma carboxyglutamate (Gla) residues -vit K is necessary for conversion of protein-bound glutamate residues into gamma carboxyglutamate residues (Gla)
fat soluble vitamins
require fat for absorption and transport -follow lipids for entry/exit out of intestinal cells -transported via chylomicrons and other lipoproteins to target tissues -stored in body in appreciable amounts -deficiency less common in US -toxicity more common than w/ water soluble vitamins
animal form of vit A
retinoid -in egg yolks, butter, whole milk products, liver, fish oils
supplemental form of vit A
retinyl palmitate, I-carotene -in US, low fat dairy products, some juices, and breakfast cereals are supplemented (~500 IU/serving) -supplements may contain from 3000 to 25000 IU/tablet ---RDA 5000 IU/day
vitamin A assessment for nutriture
serum retinol--insensitive to early deficiency and nonspecific -serum carotenoids (reflect immediate dietary intakes) -Relative dose response
water soluble (vitamins) characteristics
vitamin C, B vitamins -required in miniscule amounts, not stored in body in appreciable amounts, excreted in urine when plasma levels are high, unlikely to be toxic except in mega doses, and most are involved in energy metabolism
functional tests for vitamin K status
bleeding time: lancet stab, blood clot w/in 5 min -clotting time: collected venous blood requires 6-10 min to clot -prothrombin time (PT): time required for fibrin to form (measures factor II). Normal is 11-13 sec, issue if more than 25 -partial thromboplastin time (PTT): measures clotting factors. Serum is treated w/ activiated thromboplastin and clotting time is recorded -serum prothrombin conc -platelet count
thiamin in body
body contains 30 mg of thiamin, half in muscle and half in other organs and tissues -excreted in urine in either free or metabolized forms: -4-methylthiazole-5acetic acid -2-methyl-4-amino-5-pyrimidine carboxylic acid
vitamin A antioxidant
both vitamin A and carotenoids sequester free radicals, but carotenoids are more potent -beta-carotene, lutein, lycopene
vitamin K food soruces
broccoli=150-200ug spinach=300-400ug parsley=500-600ug margarine=20-150ug egg yolk/liver=100-150ug potatoes=1ug
carotenoids reaching liver
carotenoids can either: 1) small portion may be cleaved to form retinol 2) some may be incorporated into VLDL synthesized in the liver 3) some can be stored in the liver
vitamin A functions cont
cellular differentiation (retinoic acid) -growth (retinoic acid, retinol) -fertility (retinol) -immunity (retinoid/carotenoids) -skin integrity (retinoic acid) -bone development (all forms) -gene expression and cell development -needed by epithelial cells in lungs, trachea, skin, and GI
history of vitamins
certain diseases were related to foods/their deficiency: -scurvy: eating lemons -night blindness: eating liver -Beriberi: associated w/ eating polished rice -Pellagra: associated w/ eating corn -Rickets: treated w/ liver oil
vitamin A deficiency
common in developing countries -night blindness, retarded growth, anorexia, increased susceptibility to infection, keratinization of mucous membranes of respiratory, alimentary, urinary tracts, skin, and epithelium of eye
assessing vitamin E status
-serum tocopherol conc -tocopherol levels in adipose tissue and RBC -erythrocyte hemolysis -breath pentane measurement
conversion factors for vit A metabolites
1 retinol activity enquivalent (RAE)=1 ug retinol; 12 ug Beta carotene, and 24ug other provitamin A carotenoids
vitamin E (Tocopherol)
8 different "vitamers" -two groups of 4 isomers: alpha, beta, gamma, delta -tocopherol and tocitrienols
Vitamin K DRI
90mg/day and 120mg/day for adult men/women
Thiamin deficiency
RBC transketolase which is enzyme involved in hexose monophosphate shunt -24 hr urinary excretion of thiamin or its metabolites -thiamin load test --involves giving 5mg oral dose of thiamin ----if urinary thiamin excretion is less than 20ug, indicates deficiency
vitamin E deficiency
True deficiency is rare -occurs in 3 situations: 1) ppl cannot absorb dietary fat 2) premature, low birth weight infants. <1500grams or 3.5lb 3) rare disorders of fat metabolism
membrane and nerve conduction (thiamin)
aberrations in nerve fxn may be due to lack of energy -could regulate nerve impulse transmission by phosphorylation/dephosphorylation
vitamin E absorption/storage
absorbed as free form and follows lipids in entry/exit out of intestine and transported as lipids -stored mostly in adipose tissue and some in liver
vitamin A absorption
absorption and transport follows that of lipids -retinoid absorption: 70-90% -carotenoids: 20-50%(decrease intake, increase absorption)
Vitamin A RDA
adult women: 700 RAE adult men: 900 RAE or ~5000IU
vitamin E synthesized
all metabolites are synthesized in plants, especially rich in seeds, bran, and germ sections of plants -oils are best sources. In food, 75%=alpha tocopherol, 20%=beta tocopherol, and 5%=alpha tocotrienol -found in fatty tissues in animals and is inferior source compared to plants
vitamin E functions
antioxidant and maintains membrane integrity -not only in cell membranes, also w/in cell (mitochrondria, ER) --terminates chain-propagation rxn involving lipid peroxyl radicals (provides H from its C-6 hydroxyl group) --in process, Vit E is oxidized (tocopherol radical) and must be regenerated ----requires vit C, glutathione, and NADP
vegetable form of vit A
carotenoids -in green, red, orange, and yellow veggies -more than 600 forms: 50 are known to have vit A fxn
vitamin A digestion
carotenoids and/or retinyl esters are bound to protein and hydrolysis occurs w/ pepsin and other proteolitic enzymes (lipases, esterases) -after being released, these retinoids and carotenoids are solubilized into micellar soln and diffuse through mucosal cells into lymph
BCAA metabolism (thiamin)
decarboxylation of branched-chain alpha-keto acids that arise from valine, isoleucine, and leucine
hematopoietic b vitamins
folic acid, vitamin B12, vitamin B6, and pantothenic acid
wet beriberi
edematous -heart enlargement, arrhythmias, hypertension -Na and water retention--edemia ----excessive CHO loads and strenuous exercise could result in this type
excessive Vitamin A intake
elderly in jeopardy--diminished liver clearance -leads to bone abnormalities and increased susceptibility for fractures
B complex vitamins
energy releasing, hematopoietic, and other
vitamin A functions
essential for vision and systemic fxns -cellular differentiation -growth/reproduction -bone development -immune system
procoagulant factors
factors II (prothrombin), VII, IX, and X -all help in blood clotting
Thiamin
first discovered vitamin in 1897 -in 1912, found it to be an amine and essential for life, therefore vital amine, or VITAMINE
other b vitamins
vitamin B6, thiamin, folic acid, vitamin B12, and niacin (B3)
osteocalcin (vit K function)
marker of bone turnover -small protein containing 3 Gla residues per molecule -synthesized by osteoblasts. When made, 70-80% is bound to hydroxyapatite and rest stays in circulation -binds to hydroxyapatite -patients w/ osteoporosis, circulating osteocalcin is undercarboxylated -high levels and low serum vit K are associated w/ lower BMD and higher risk for fractures
relative dose response (RDR)
measures vit A stores in liver -detects DBP released from liver --first measure of fasting plasma retinol --give oral dose of vit A -measure plasma retinol 5 h later ----if stores are depleted, plasma retinol will markedly increase after 5 hours, due to its binding to apo-RBP in liver and then released as holo-RBP
prolonged thiamin deficiency
mental confusion, ataxia, peripheral paralysis ophtalmophlegia (eye muscle), tachycardia -leads to BERIBERI
thiamin absorption and metabolism
must be free (not phosphorylated) to be absorbed -active transport (low conc) -passive transport (high conc) -thiamin in blood is usually in the monophosphate form (TMP) and bound to albumin for further transport ---free thiamin can be phosphorylated in liver or other tissues
serum tocopherol concentration
need to calculate ratio: vit E/total lipids (>0.6 is adequate) -more lipids consumed, higher the conc
target organs for Vit E
neuromuscular, vascular, and reproductive -deficiency is related to the lack of antioxidant leading to cell damage
vitamin E toxicity
one of the least toxic and at high doses may antagonize the utilization of other fat soluble vitamins
extrahepatic Gla proteins associated with calcified tissues
osteocalcin and matrix-gla protein (synthesized by osteoblasts in bone) -plaque Gla-protein (in artherosclerotic plaques) -others--isolated from renal stones and urine
Population at risk for vit E deficiency
people w/ fat malabsorption ---cystic fibrosis and other hepatobiliary disorders -premature, low birth infants ---limited transplacental movement
vitamin A deficiency risk
people w/ malabsortive disorders: steatorrhea, pancreatic, liver or gallbladder disease, intestinal parasites ---in alcoholics, celiac disease, cystic fibrosis, and other intestinal probllems -premature babies (low liver storage)
dry beriberi
peripheral neuropathy -loss of sensory, motor and reflex function in periphery -tingling, numbness, burning sensation of feet -muscle wasting
vitamin K
phylloquinone, menaquinone, and menadione -all three are active -mostly stored in liver, although body pool is small for fat soluble vitamins (50-100ug)
fat soluble
soluble in fat and fat solvents, excess intake stored in body, small amounts excreted in bile, deficiency syndrome slow to develop, -not absolutely necessary in diet every day -absorbed into lymphatic system and follow lipid transport -some have precursors or provitamins -needed by higher organisms -may be toxic at low levels (6 to 10 times RDA)
water soluble
soluble in water, minimal storage of dietary excess, excreted in urine, deficiency symptoms may develop rapidly -needed in everyday diet -absorbed into blood via portal vein -do not have precursors -needed by both simple and complex -toxic at megadose (>10 times RDA)
menaquinone (K2)
synthesized by gut bacteria (in colon) and usually available for absorption by host ---may provide up to 50% of total -contain functional naphthoquinone ring and aliphatic side chain -side chain is composed of varying number of isoprenoid residues
menadione (K3)
synthetic form
energy releasing b vitamins
thiamin (B1), riboflavin (B2), Niacin (B3), Pantothenic acid, biotin, and vitamin B6
thiamin
thiamin pyrophosphate (TPP), also called thiamin diphosphate (TDP) AND thiamin triphosphate (TTP)
thiamin sources
ubiquitous in small amounts in all foods and not destroyed by regular cooking -liver/yeast is highest amount -whole or enriched grain products and cereals, meats (pork), and legumes are best sources -rice and refined products are poorest sources -enzyme thiaminase is present in raw fish or tannic and caffeic acids destroy about 50% of thiamin
thiamin toxicity
usually doesn't occur w/ oral doses (500mg/d for 1 month) -may occur w/ parenteral, intravenous or intramuscular route (100x rec) ---headache, convulsions, cardiac arrhythmia