ns 1150 - prelim 3

difference between vitamins & minerals

vitamins

• organic

• can be self-synthesized

• plant sources: precursors/provitamins 🡢 converted in body

• animal sources: active/coenzymes 🡢 used directly

• needed in small amounts (most out of water-soluble is vit. C, most out of lipid-soluble is vit. E)

• main purpose is to serve as coenzymes organic molecules that attach to enzyme and activates enzyme’s metabolic activity

minerals

• inorganic

• cannot be self-synthesized

• animal-based sources are more bioavailable than plant-based

• lost in form of sweat, stored in bones, liver, tissues

• can differ in amts needed (iron needed in trace amts, calcium is needed in major amounts) 

• purposes can range from being cofactors for DNA synthesis, repair and ATP cycle

• toxicity is rare due to constant regulation & low storage

types of vitamins

water-soluble

1. B₁ (thiamin)

2. B₂ (riboflavin)

3. B₃ (niacin)

4. B₉ (folate)

5. B₁₂ (cobalamin)

6. C (ascorbic acid)

---

• short-term supply (daily intake)

• lowered risk of toxicity

• absorbed into blood

• less stable in handling process

fat-soluble

1. A

2. D

3. E

4. K

---

• long-term supply (regular intake)

• increased risk of toxicity

• absorbed into lymphatic system (requires lipoproteins)

• more stable in handling process

roles of vitamins/minerals

• nrg production: vit. B_1, vit. B₂, vit. B₃

• bone health: calcium, vit. D, vit. K

• eye health: vit. A

• blood health: vit. B₉, vit. K, vit. B₁₂

• antioxidants: vit. C, vit. E

vit. B₁ (thiamin)

• function: acts as coenzyme that assists in the production of acetyl-coA

  • thiamin + 2 phosphate 🡢 thiamin diphosphate (TPP) to assist in TCA cycle

• deficiency: beriberi

  • wet beriberi - edema (cardiovascular damage)

  • dry beriberi - muscle weakness (nerve damage)

  • infantile beriberi

• rda: 1.1 mg (no UL); sources: fortified cereal, whole grains, pork

  • bioavailability decreased by alcohol; wernicke-korsakoff syndrome, neurological dmg

vit. B₂ (riboflavin)

• function: acts as coenzymes for electron carriers (redox)

  • riboflavin 🡢 flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD) to transport high nrg e^- from TCA to ETC, breaks down fatty acids to acetyl-coA

• deficiency: ariboflavinosis **RARE

  • cheilosis (cracked lips), glossitis

• rda: 1.1mg (no UL); sources: meat, dairy, fortified cereals

vit. B₃ (niacin)

• function: acts as coenzyme for electron carriers (redox)

  • niacin 🡢 nicotinamide adenine dinucleotide (NAD) 🡢 NADP, carries H⁺ from TCA to ETC

• deficiency: pellagra

• rda: 14mg (UL of 35mg); sources: meat, mushrooms, fortified cereals

  • niacin equivalent (NE): unit to include both niacin and its precursor, tryptophan, in the total niacin intake

  • toxicity: nicotinic flush

vit. D

• function: maintains Ca²⁺ homeostasis in bones, regulating cell differentiation

  • vit. D₂: ergocalciferol

    • can be obtained from diet or supplements

    • from diet: fat-soluble vitamins require bile salts 🡢 enterocytes 🡢 chylomicrons 🡢 liver 🡢 VLDL to fat and tissues

  • vit. D₃: cholecalciferol **more bioavailability

    • can be obtained from diet, supplements or self-synthesis

      • self synthesis: 7-dehydrocholesterol + UVB

      • self-synthesis may be hindered by high lvls of melanin, and increased age

    • from diet: requires chylomicrons

    • from skin: enter blood 🡢 liver

  • vit. D_2/3 🡢 in liver: hydroxylated into [25(OH)D], 25-hydroxyvitamin D 🡢 in kidney: hydroxylated into [1,25(OH)D], calcitriol (ACTIVE FORM) 🡢 increases overall Ca²⁺ levels

  • assists in Ca²⁺ homeostasis

    • low lvls of Ca²⁺ in blood 🡢 PTH production 🡢 increases kidney’s conversion of 25(OH)D to 1,25(OH)D

• deficiency: 

  • in children: rickets, deformed growth

  • in adults: osteomalacia, softened bones

    • inadequate bone mineralization

  • in elderly, postmenopausal women: osteoporosis: increased risk of fracture from brittle bones

    • bone mass loss (resorption, esp. when higher than formation

• rda: 15mg/600IU (UL of 100mg/4000IU); sources: D₃: dairy products, fatty fish, cod liver oil, D₂: mushrooms (UV-grown)

  • toxicity: kidney stones, calcified blood vessels

vit. K

• function: 1) improve bone mineralization thru osteocalcin synthesis, improve osteoclast function and increase osteoblast apoptosis thru prod. of osteocalcin 2) activate blood clotting factors

  • K₁: phylloquinone (plant foods)

  • K₂: menaquinone (animal foods, fermented, gut-produced)

  • K₃: menadione (synthetic, animal feed)

  • inactive clotting factors + Ca²⁺ + Vit. K 🡢 active clotting factors 🡢 convert prothrombin to thrombin 🡢 convert fibrinogen, soluble to fibrin, insoluble strands

• deficiency: neonatal bruising (due to lowered vit. K in babies)

  • all babies should have intramuscular injection of vit. K

• rda: 100mg (no UL); sources: dark leafy greens, black-eyed peas

  • bioavailability influenced by 1) antibiotics 2) warfarin — anti-coagulant 3) fat malabsorption syndromes

calcium

• function: necessary for bone formation

  • bones + Ca²⁺ 🡢 hydroxyapatite crystals 🡢 protein collagen matrix 🡢 mature bone

• deficiency: osteoporosis

• rda: 1000mg (UL of 2500mg); sources: dairy products, cooked leafy greens, bony fishes

  • toxicity: kidney stones, interference with absorption of other minerals

  • bioavailability influenced by anti-nutrients

    • oxalic acids: spinach, red-green veggies

    • phytic acids: wheat bran, legumes

which vitamins/minerals have ULs?

calcium, iron, vit. D, vit. B₃, vit. B₉, vit. C, vit. E

fortification vs. enrichment of foods

fortification

• related to DV

• adding nutrients that weren’t present previously, during processing

• prevents population deficiencies, restores lost nutrients, balances vegan products

enrichment

• regulated by FDA

• only certain foods are: whole grains

• bran, germ removed 🡢 refined grains, pellagra and beriberi

• standard of identity: B₁, B₂, B₃, folic acid and iron are added to flour

vit. B₉ (folate/folic acid)

• function: DNA synthesis & repair, neural tube development, amino acid metabolism, regulation of gene expression through methylation

  • folic acid/folate 🡢 tetahydrofolate (THF) coenzyme 🡢 accepts 1-carbon units to power methyl group transfer rxns

• deficiency:

  • megaloblastic macrocytic anemia (in conj. with vit. B₁₂) huge, nucleus bond RBCs

    • fatigue, shortness of breath

  • congenital heart defects & neural tube defects

    • spina bifida, bubble of exposed neural tissue

    • anencephaly, lack of developed brain

• rda: 400microg (UL of 100microg) **higher for pregnant women; sources: legumes, spinach, fortified cereal

  • bioavailability is influenced by 1) decreased availability from lowered dietary intake, alcoholism, malabsorption 2) increased demand from pregnancy, sickle cell disease 3) damage from cooking

vit. B₁₂ (cobalamin)

• function: ATP production, amino acid metabolism, regulation of gene expression through methylation

  • because tightly bound, requires specific absorption pathway

    • mouth: haptocorrin is bound to food protect from HCl

    • stomach: pepsin separates protein & B₁₂ & parietal cells secrete intrinsic factor (IF)

    • small intestine: haptocorrin-B₁₂ compound is split and released B₁₂ binds to IF to form absorbable complex

• deficiency:

  • megaloblastic macrocytic anemia (in conj. with vit. B₉) huge, nucleus bond RBCs

    • fatigue, shortness of breath

  • pernicious anemia: autoimmune disease destroys parietal cells that produce IF, lack of binding causes B₁₂ to be flushed out

  • **population at risk: vegans, elderly

• rda: 2.4microg (no UL); sources: beef liver, clams, seafood

  • bioavailability influenced by GERD/ulcer medications that inhibit HCl activity

iron

• function:

  • cellular respiration

  • transporter of gases (hemoglobin, heme-bound iron) 

    • O₂ to tissues, CO₂ away from tissues

  • oxygen reservoir (myoglobin)

  • cofactor for detoxifying and antioxidant enzymes

heme-bound iron (Fe²⁺)

• better absorbed

• animal sources

non-heme, free iron (Fe³⁺)

• poorly absorbed

• plant sources

• iron pathway

  • Fe³⁺ 🡢 Fe²⁺

    • in blood: circulated via ferroportin (FPN)

    • in enterocyte: stored as ferritin

    • in liver: creates hepcidin to regulate iron by degrading ferroportin carriers of iron

      • low iron levels will ↓ hepcidin to increase iron absorption by sending out the iron stores in the enterocyte

      • high iron levels will ↑ hepcidin to degrade ferroportin to prevent mobilization in the Fe³⁺ form, which is dangerous as it is a free radical 

• deficiency: microcytic hypochromic anemia (smaller RBCs, less iron carried)

  • can be caused by decreased availability from inflammation, CKD, general blood loss, vegan diet, or increased needs from being pregnant

  • **most common deficiency, at risk popn: children, women of reproductive age

• rda: 15mg (UL of 45mg); sources: meat, seafood, spinach

  • toxicity: vomiting, diarrhea, constipation, black stool

    • can be side effect of hereditary hemochromatosis that ↓ hepcidin, which will increase iron absorption

  • bioavailability can be inhibited by phytates (plant seeds), polyphenols (teas/coffees), oxalates (spinach, dark chocolate) and enhanced by vit. C and meat sources

vit. A

• function: 

  • eye health (maintains cornea, converts light nrg into nerve impulses @ retina)

  • growth & differentiation of cells

  • immunity

  • reproduction

• provitamin (carotenoids, e.g. β-carotene) 🡢 retinal 🡢 interconverted with retinol (transportable form) 🡢 one way conversion with retinoic acid (cell differentiation)

  • nonprovitamin carotenoid cannot be converted to vit. A

  • preformed vit. A comes in forms of vit. A, not carotenoids (animal sources/supplements)

• visual cycle: circulation of retinol 🡢 cis-retinal, combined with opsin = rhodopsin 🡢 exposure of light to rods, cis-retinal becomes trans-retinal 🡢 sends signal to brain and cis-retinal regenerates along with rhodopsin

• deficiency:

  • loss of night vision

  • xerophthalmia (permanent dmg to cornea, blindness)

    • without constant input of cis-retinal (vit. A, prod of rhodopsin impaired, unable to send signals to brain)

  • impaired wound healing

  • stunted growth in children

• rda: 800 RAE (no UL for carotenoids, UL of 3000microg for preformed vit. A ** RARE); sources: carrots, peppers (carotenoids), liver (preformed vit. A)

  • retinol activity equivalents (RAE): unit to include both retinol and its precursor, β-carotene, in the total retinol intake

which vitamins are antioxidants?

• vit. C & E

  • act as compounds that stabilized/oxidize (donate e^-) to free radicals (ROS, RNS) which cause damage to DNA and cell membranes (lipid peroxidation)

vit. E

• function: prevents lipid peroxidation by free radicals by donating e^- to ROS

  • tocopherol & tocotrienols

    • α-tocopherol is most biologically active form

      • can be regen by vit. C

• deficiency: hemolytic anemia (ruptured RBCs) **RARE

• rda: 15mg (UL of 1000mg); sources: vegetable oils, nuts, seeds

  • toxicity: hemorrhage (interferes with vit. K and blood clotting) **RARE

vit. C

• function:

  • synthesis of collagen

  • antioxidant (regens α-tocopherol by oxidizing reduced vit. E)

  • synthesis of neurotransmitters & carnitine

  • coenzyme for iron

• deficiency: scurvy (slow healing of wounds, gum bleeding) **RARE IN DEV. COUNTRIES

• rda: 80mg (UL of 2g); sources: citrus fruits, peppers, broccoli

  • toxicity: prevent GI distress

  • bioavailability enhances iron absorption, but decreased by cooking

water

• function (65% of our body is water)

  • maintain body’s blood volume & phospholipid membrane

  • regulate body temperature

  • lubricant around joints

intracellular (ICF)

• more H₂O

• K⁺

extracellular (ECF)

• less H₂O

• affected by external events

• Na⁺, Cl^-

• H₂O always goes towards higher [] of solutes

• Na⁺ levels used to determine body’s water content

  • Na⁺ in ECF ↓ = body water content ↑

retention

• antidiuretic hormone (ADH)

  • pituitary gland

  • promotes H₂O retention in kidneys

  • reduces urinary loss of H₂O

• aldosterone

  • adrenal gland

  • stimulates sodium absorption in kidneys

  • water retention thru aquaporins

release

• natriuretic peptides

  • cardiac muscle cells

  • block release of ADH and aldosterone

  • stimulates Na⁺ and H₂O loss in kidneys

  • reduces BP

PICO

• Population/patient

• Intervention/exposure

• Comparator

• Outcome

introduction

• objectives

• hypothesis

methods

• study design

  • was assignment random or self-selected?

    • counterbalanced design prevents imbalances from random selection

    • crossover design assigns same subject to undergo both placebo and treatment

  • what is the sample characteristics?

    • small sample size, less reliable

    • is the sample comparable to the population

    • is the study on cells, animals or humans

    • were external variables controlled for?

  • statistical analysis plan

    • internal validity: can study accurately measure causal reln

    • external validity: can findings be applied to broader population?