Midterm 1 Material Flashcards

Question

Define AI.

Answer 1

Adequate intake Daily intake level that appears to be sufficient based on observed or experimentally determined approximations of nutrient intake by a group (or groups) of healthy people. The AI is used when there is not enough evidence to determine a requirement (and thus EAR/RDA) for a nutrient – in other words, we do not know how much we actually need. The AI is an amount that is estimated to be enough for daily intake. Because the AI is not based on nutrient requirements, we cannot make estimates about the number of people meeting their requirements for a nutrient using the AI (as we can for the RDA and EAR).

Answer 2

Adequate intake Daily intake level that appears to be sufficient based on observed or experimentally determined approximations of nutrient intake by a group (or groups) of healthy people. The AI is used when there is not enough evidence to determine a requirement (and thus EAR/RDA) for a nutrient – in other words, we do not know how much we actually need. The AI is an amount that is estimated to be enough for daily intake. Because the AI is not based on nutrient requirements, we cannot make estimates about the number of people meeting their requirements for a nutrient using the AI (as we can for the RDA and EAR).

Answer 3

Tolerable Upper Intake Level The highest level of daily nutrient intake that is likely to pose no risk of adverse health effects to almost all individuals in the general population.

Answer 4

Planning and assessing diets for individuals or groups. Individuals should aim to meet the RDA or AI for each nutrient. Consuming less than the RDA or AI may lead to inadequate intakes. To be safe, nutrient intakes should be below the UL. Intakes above the UL may be associated with adverse effects.

Answer 5

Estimated energy requirement Average dietary energy intake that maintains energy balance and good health for a given life stage, gender, and physical activity level

Answer 6

Acceptable Macronutrient Distribution Range Range of intake for macronutrients that provides adequate essential nutrients and reduces risk of chronic disease. For adults: Carbs: 45-65% Fat: 20-35% Protein: 10-35%

Answer 7

Vitamin K (named for **Koagulation (Danish for coagulation))** is a fat soluble vitamin important in blood clotting and bone health. Phylloquinone, K1: (plant sources) has a saturated tail and are always the same length. Some will be converted to K2 in the body. Menaquinone, K2: (animal and bacterial sources) has an unsaturated tail and may have repeating units. Emerging evidence suggests K2 may be more potent and have greater effects in the body. Functionally otherwise the two forms are equivalent. *Note: Structures are not examinable.*

Answer 8

Plant foods → phylloquinone → richest sources are leafy green vegetables and plant oils Other foods → menaquinones → fermented foods like saurkraut (produced by bacteria), dairy products & meats. Supplemental forms → often contains both K1 and K2 Other sources → intestinal anaerobic bacteria synthesize menaquinones (not sufficient to meet needs, but some is provided)

Answer 9

Fat soluble compounds like vitamin K require **emulsification** with bile salts for effective digestion & absorption. No breakdown is required, but micelle formation is required for uptake

Answer 10

Fat soluble vitamins like vitamin K passively diffuse into enterocyte (absorptive intestinal cells) and form lipoproteins called chylomicrons which enter the lymphatic system via the lacteal (too large to enter bloodstream directly) Absorption differs depending on the source. Dietary K1 and K2 are absorbed mainly in the jejunum, incorporated into micelles, then passively diffused into enterocyte (receptor mediated uptake may also account for some vitamin K uptake) and packaged into chylomicrons. K2 from bacterial synthesis absorbed in ileum and colon via passive diffusion; process less well understood; absorption capacity differs among individuals.

Answer 11

Vitamin K is released from enterocytes in chylomicrons. Chylomicrons leave the intestinal mucosal cell via exocytosis. They enter the lacteal to lymphatic circulation. They later enter the bloodstream via the thoracic duct (near the heart) at a very slow rate. Chylomicrons deliver vitamin K to body cells; remaining vitamin K ends up in the liver in chylomicron remnants; the liver metabolizes vitamin K or repackages vitamin K in VLDL; VLDL is exported from the liver and delivers lipids and vitamin K to body cells.

Answer 12

Main circulating form = phylloquinone Vitamin K is stored in cell membranes in very low amounts. Overall body storage estimated 50–100mcg (smaller than that of vitamin B12) Rapid metabolism of vitamin K in liver → either packaging into VLDL for transport to other tissues or degradation/oxidation for excretion.

Answer 13

Phylloquinone: almost completely metabolized; oxidation of side chain and conjugation with glucuronic acid Menaquinone: little is known

Answer 14

Conjugated metabolites excreted with bile in feces (main) or urine (minor)

Answer 15

* Vitamin K is required to catalyze the carboxylation of glutamic acid residues in Gla proteins that allows the high-affinity binding Ca²⁺ ions. * Gla proteins are involved in blood coagulation (thrombin, prothrombin, factor VII, factor IX, factor X, and others) * Gla-proteins can bind calcium after carboxylation of glutamic acid residues by vitamin K, which then allows reaction with other cell components like phospholipids to affect blood clotting and bone mineralization, among other processes.

Answer 16

Vitamin K antagonists = pharmacological anticoagulants/blood thinners (e.g., Warfarin). These anticoagulant drugs reduce thrombotic effects and occurrence/recurrence of heart attacks by interfering with vitamin K cycle. This reduces vitamin K activity and prevents blood clots. This is important in high risk individuals since blood clots increase potential heart attack and stroke events. The reduction of vitamin K is a critical conversion step for vitamin K to function in gamma carboxylation reactions of glutamic acids. Anticoagulants interfere with the activity of quinone reductase and epoxide reductase.

Answer 17

Higher prevalence of suboptimal status than deficiency. 1. **Impaired bone metabolism** → diminished bone mineral density; increased fracture rates 2. **Cardiovascular health** → CVD risk increase; inflammation; arterial calcification

Answer 18

Vitamin K deficiency is most likely to occur in **newborns;** could result in vitamin K deficiency internal bleeding that can be fatal; national prevention strategy → intramuscular injection for newborns Newborns are at risk for deficiency because: 1. Low stores at birth due to poor placental transfer of vitamin K from maternal to fetal blood. 2. Low levels of vitamin K in breast milk 3. ‘Clean-gut’ = low gut synthesis of vitamin K by intestinal bacteria

Answer 19

Individuals at risk for developing suboptimal vitamin K status and vitamin K deficiency: * low dietary vitamin K intake * fat malabsorptive disorders: * cystic fibrosis * obstructive jaundice (blocking bile flow from liver) * inflammatory bowel disease * chronic pancreatitis (inflammation of pancreas) * liver disease * Chronic treatment with antibiotics due to lack of vitamin K synthesis from gut bacteria

Answer 20

**Vitamin A and E = antagonists of vitamin K** * Vitamin E: * Inhibition of phylloquinone metabolism * increase in hepatic oxidation and excretion of all forms of vitamin K * Excess intake of vitamin A and E → impair vitamin K absorption

Answer 21

Insufficient evidence to derive Estimated Average Requirement values → derivation of Adequate intake values for the entire population Answer → D (can't give a percentage because we don't actually know the requirement, AI is given based on what we *think* is enough based on intake levels of healthy populations)

Answer 22

Emulsification with bile salts

Answer 23

Absorption can be **enhanced** by dietary fats. Absorption can be **impaired** by fat malabsorption disorders.

Answer 24

A droplet of fat present in the blood or lymph after absorption from the small intestine.

Answer 25

Answer → C A would be correct if ‘chylomicron’ was replaced with ‘micelle’.

Answer 26

Answer → B Fat soluble vitamins in general are more likely to be stored and cause toxicity, but vitamin K is an exception to this. Vitamin K has small stores in the body and is excreted efficiently so toxicity is not likely. There is no UL for vitamin K because there has been no observed adverse effects or benefits of high intakes.

Answer 27

Answer → D When people are put on anticoagulants, they are titrated to ensure people are given enough to decrease blood clotting, but not entirely. They are given the right dose for their body and for their current intake. Eating too much vitamin K could override the effects of the anticoagulants.

Answer 28

Role of vitamin K in bone mineralization. * **Osteocalcin (bone Gla-protein, BGLAP)** * Secreted by osteoblasts during bone formation; involved in bone mineralization * **Matrix Gla-protein (MGP)** * Found in bone, dentine and cartilage; associated with bone extracellular proteins; promotes bone calcification; **inhibitor of calcification of soft tissue (protects soft tissues from calcification)**

Answer 29

Answer → A

Answer 30

1. GLA proteins implicated in cell proliferation (i.e., might suggest a link with cancer) and apoptosis, and inflammation 2. Gene expression (can affect bone/heart health as well)

Answer 31

1. Prevention of cardiovascular disease 2. Glucose control & prevention of type 2 diabetes 3. Prevention of osteoporosis 4. Cancer prevention/treatment 5. Potentially more?

Answer 32

Severe deficiency = impaired blood clotting (hemorrhage); rarely occurs in health adults In Canada, no representative data available on vitamin K status or dietary vitamin K intake

Answer 33

Answer → D

Answer 34

Answer → D

Answer 35

Binding and transport of oxygen Energy metabolism Cofactor for various enzymes Antioxidant protection Antimicrobial function

Answer 36

* **Heme iron** * Liver, red meat, seafood * **Non-heme iron (mostly Fe³⁺ ferric form)** * Spinach, collards, broccoli, grains * ~50% of iron in animal foods is non-heme * Mandatory by law in Canada (governed by Food and Drug Regulations through the Food and Drug Act) → **flour fortification with non-heme iron**

Answer 37

* Hemoglobin/myoglobin → Hydrolysis of heme iron from globin portion catalyzed by protease in stomach/small intestine. * Heme remains soluble → absorption intact in duodenum and proximal jejunum. * Carrier-mediated transport (hcp1) across brush border * In enterocyte, release of iron from heme in Fe²⁺ form * 25% of heme iron from foods is absorbed

Answer 38

* DIGESTION → Non-heme iron bound to components of food → hydrolysis of iron, mostly in form of Fe³⁺ catalyzed by hydrochloric acid in the stomach & by protease in stomach/small intestine. * ABSORPTION → Fe³⁺ reduced to Fe²⁺ prior to absorption → reduction partially achieved in the stomach; however, mostly through reductases in brush border membrane; carrier mediated transport with DMT1 (divalent mineral transporter 1) across brush border membrane (= regulatory step of iron absorption → synthesis of DMT1 affected by iron status.

Answer 39

Iron transport in plasma bound to transferrin; uptake by cells via transferrin receptor.

Answer 40

Iron storage protein = ferritin (in all cells) Organs with the highest storage: * Liver * Bone marrow * Spleen Most iron is bound to proteins or in heme → free iron can act as a pro-oxidant (recall: fenton reaction)

Answer 41

The human body has no pathways or mechanisms to excrete iron. _Metabolism_ * High recycling of red cell iron by reticuloendothelial system (RES) * Macrophages in spleen, liver, & bone marrow * Iron released from macrophages via ferroportin _Excretion_ * No iron excretion mechanism in human body but losses of iron: * Blood loss * Losses in bile and desquamated mucosal cells * Skin losses * Losses through urine

Answer 42

**Ferrous forms better absorbed**. Heme iron is ferrous iron (Fe²⁺) and it comes from animal foods. Non-heme iron is ferric iron (Fe³⁺) and it comes from vegetarian foods. Since Fe³⁺ needs to be reduced to Fe²⁺ prior to absorption, Fe²⁺ iron is considered more bioavailable.

Answer 43

_Enhancers_ * acids (e.g., ascorbic, citric, lactic acid) * acidic pH * Meat, fish, poultry (MFP) factors * Sugars (fructose and sorbitol) _Inhibitors_ * (1) Polyphenols such as derivatives found in tea and coffee (can reduce absorption by up to 50%) * (2) Oxalic acid found in spinach, chard, berries, chocolate, tea, and others (binds iron so it is not absorbed) * (3) Phytic acid, found in whole grains, legumes, lentils and seeds * (4) Some minerals, such as calcium, zinc, and manganese

Answer 44

Whole body iron is regulated through a network of signals between **cellular needs & uptake, cellular iron storage & absorption** in response to iron status indicators. Iron losses must be balanced with intake. Total body iron is regulated at the level of absorption. When body stores are adequate, less iron is absorbed. When body stores are low, more iron is absorbed (DMT1 increase). Iron intake → regulated process Iron loss → unregulated process _Hepcidin_ * Regulatory protein of iron absorption (acts like a hormone) * Released from liver in conditions of high iron status (high transferrin saturation) * Decreases absorption of iron and release of iron from macrophages through destruction of ferroportin

Answer 45

**Stage 1: Iron depletion:** Iron stores decline → serum ferritin drops **Stage 2: Iron deficiency erythropoeisis**: Circulating iron decreases → less iron to tissues → decline in iron-dependent enzyme activity → symptoms like weakened immune systems (or other) may result **Stage 3: Iron deficiency anemia**: Decline in immunologic and neural functioning → impaired oxygen delivery to tissues: paleness, fatigue, shortness of breath

Answer 46

**Stage 1: Iron depletion:** Iron stores decline → serum ferritin drops **Stage 2: Iron deficiency erythropoeisis**: Circulating iron decreases → less iron to tissues → decline in iron-dependent enzyme activity → symptoms like weakened immune systems (or other) may result **Stage 3: Iron deficiency anemia**: Decline in immunologic and neural functioning → impaired oxygen delivery to tissues: paleness, fatigue, shortness of breath

Answer 47

**Lower intake/absorption →** vegetarians, vegans, gastrointestinal disease (e.g., ulcerative colitis) **Higher losses/demands →** menstruating, blood loss, hookworm, infants and children, pregnant people

Answer 48

* **Functional iron** * Hemoglobin concentration * Red blood cell size (MCV) or hemoglobin content (MCH) * Serum transferrin receptor * **Iron transported to tissues** * Serum iron * Serum total iron binding capacity (TIBC); transferrin * Transferrin saturation * **Iron stores** * Serum ferritin * Iron content in liver/bone marrow

Answer 49

Iron exists in several oxidation states, but it is only stable in the body's aqueous environment in food as ferrous or ferric iron. Iron is also found in the body in heme form.

Answer 50

Answer → A Heme iron is absorbed better than non-heme iron.

Answer 51

Heme iron **25%** absorbed Mixed diet **18%** absorbed Vegetarian diet **10%** absorbed

Answer 52

Answer → D Acid in orange juice can reduce ferric (Fe³⁺) to ferrous (Fe²⁺) iron. Ferrous iron is more soluble, so iron absorption is enhanced.

Answer 53

Notice that menstruation and pregnancy increase RDA considerably.

Answer 54

Requirement for iron is 1.8 times higher for vegetarians/vegans.

Answer 55

1. Used by intestinal cell in a functional capacity (e.g., cofactor) 2. Stored in the storage protein ferritin (as Fe³⁺) 3. Transported across the basolateral membrane to enter circulation for transport to body tissues. 1. carrier mediated (via ferroportin) 2. coupled with oxidation of ferrous (Fe²⁺) to ferric (Fe³⁺) iron in a copper-dependent reaction (hephaestin) 3. Fe³⁺ binds to transferrin = transport protein in plasma → distribution of serum transferrin-Fe³⁺ via liver to tissues.

Answer 56

Answer → B

Answer 57

Answer → B Whole body iron is regulated only through absorption. There are no regulated excretion methods.

Answer 58

Regulation of whole body iron 1. High transferrin saturation stimulates release hepcidin from the liver 2. Hepcidin binds to ferroportin at macrophages and at basolateral membrane of the enterocyte 1. internalization + destruction of ferroportin 2. iron absorption and release into plasma is impaired

Answer 59

1. Demand for iron → release of hepcidin from the liver is stimulated by higher serum transferrin saturation (high circulating iron) via a signal cascade involving binding to the transferrin receptor 2. Inflammation (mediated by cytokines) → hepcidin is elevated during inflammatory conditions/diseases → release of iron thus decreases; serum iron pool continues to decrease; “iron starvation”; anemia develops → occurs because bacteria/pathogen also needs iron to survive; thus our bodies have evolved this unique mechanism to prevent the pathogen from accessing the iron for their own use → becomes a problem with chronic conditions.

Answer 60

* With **lower** cellular iron → increased transferrin receptor concentrations = increased uptake of iron; decreased ferritin production = decreased iron storage * With **higher** cellular iron → decreased transferrin receptor concentrations = decreased uptake of iron; increased ferritin production = increased iron storage

Answer 61

False. Ferrous (Fe²⁺) forms better absorbed.

Answer 62

True. Ferrous (Fe²⁺) forms better absorbed.

Answer 63

False. Hepcidin is released at high transferrin saturation levels

Answer 64

False. Hepcidin binds to ferroportin **preventing** iron release from the enterocyte and macrophages.

Answer 65

False. Hepcidin concentration are **inversely** correlated with iron demands.

Answer 66

False. Hepcidin also prevents release of iron from macrophages that digest and recycle the contents of red blood cells.

Answer 67

Depletion of iron stores (i.e., the first stage of iron deficiency), is most likely to affect **ferritin levels**. (A reduction)

Answer 68

Reduced number of red blood cells or decreased hemoglobin in the blood

Answer 69

Microcytic (RBCs become smaller) hypochromic (RBCs are paler) anemia.

Answer 70

Mycrocytic hypochromic anemia

Answer 71

Global issue! Despite the fact that iron is the second most abundant metal in the Earth's crust, iron deficiency is the world's most common cause of anemia. Prevalence ~1.6 billion people worldwide ***When it comes to life, iron is more precious than gold.***

Answer 72

Pregnancy is associated with increased demands for iron.

Answer 73

* **Cognitive development** and **physical growth** (infants, preschool and school-aged children) * **Cognitive performance** in adults * **Immune function**, thus morbidity from infections * **Physical capacity** and work performance

Answer 74

* Increases **perinatal risks** for mothers and neonates. * Increases overall **infant mortality**.

Answer 75

Concave nails PICA - the craving for non-food substances Restless legs

Answer 76

False. Ascorbic acid enhances iron absorption.

Answer 77

* **Low iron supply** * Low intake of iron-rich foods * Low iron absorption * higher intakes of non-heme iron, fibre, phytates, polyphenols * GI disease (e.g., IBD) * **Higher iron losses** * Menstruation or bleeding * **Higher iron requirements** * Growth & pregnancy

Answer 78

Pregnant people Vegetarians and vegans Those with GI disease (e.g., ulcerative colitis)

Answer 79

* Higher intake of iron-rich foods. * Change eating patterns to increase iron bioavailability * Food fortification with iron (flour, rice, soy-sauce, sugar) * Biofortification (iron-rich rice varieties) **Benefits** → no need for compliance, lower risk of toxicity **Limitations →** Most people with iron deficiency need a supplement to restore iron levels

Answer 80

**Benefits →** more effective for reversing iron deficiency; targeted, cost effective **Limitations →** difficult to reach large population; requires compliance (taking pills/liquids); risk of toxicity from overconsumption

Answer 81

* Daily dosage to reverse anemia = 50-100 mg of elemental iron * Side effects → nausea, constipation * Weekly supplementation recommended to reduce these side effects

Answer 82

* Iron salts e.g., ferrous sulfate, ferrous gluconate, ferric citrate, ferric sulfate) * **Ferrous forms better absorbed.** * Iron-amino acid chelates & polysaccharide-iron complexes * Good availability and may decrease side effects of iron * Heme iron * Good bioavailability but rare, costly, and animal based.

Answer 83

⅔ of total body iron in hemoglobin = biggest compartment = good functional biomarker of iron * Iron deficiency leads to _low hemoglobin concentrations_ (anemia). **Constraints** → slow indicator due to long life-time of erythrocytes (120 days); causes for low hemoglobin not only iron deficiency (folate/vitamin B12 deficiency; sickle cell disease) Low cost, fast, easy to use.

Answer 84

**Transferrin saturation** = (serum iron/serum TIBC) x 100 *How much iron is available for bone marrow and other tissues? Transferrin is the protein that moves iron in the blood. TIBC = total iron binding capacity*

Answer 85

**Ferritin = iron storage protein** Serum ferritin strongly correlates with tissue iron levels (= storage iron). Serum ferritin decrease = iron deficiency Serum ferritin increase = iron overload, inflammation, infection

Answer 86

Iron overload = too much iron is built up in the body **Symptoms →** joint pain, weight loss, and stomach pain. **Chronic overload symptoms** → enlargement of the liver (hepatomegaly liver cirrhosis)

Answer 87

Iron overload = too much iron is built up in the body _Causes_ 1. Genetic disorder (hereditary hemochromatosis) 2. Certain types of diseases, e.g., chronic liver disease 3. Chronic consumption of excessive levels of iron

Answer 88

Autosomal recessive disease Single point mutation in HFE gene in position C282Y Iron overload: 84% of homozygous → marked; 18% of heterozygous → mild Highest prevalence in Northern European counties

Answer 89

Hepcidin controls iron release and iron absorption. HFE-mutant → **low hepcidin levels** → uncontrolled iron absorption

Answer 90

* Weakness, weight loss * Joint and abdominal pain * Enlargement of the liver (hepatomegaly 95%) * Liver cirrhosis; liver cancer (30%) * Damage to pancreas, diabetes (30-60%)

Answer 91

at age \> 40 years Men outnumber women 3:1

Answer 92

Phlebotomy Chelation therapy Vegetarian diet

Answer 93

* **Acute iron poisoning from supplemental overdose** → most commonly in children younger than age 6, potential cause of fatal poisoning * **Consequences of acute iron poisoning** → irritation of GI tract, and, possibly, irreversible damage to GI tract and liver

Answer 94

In someone with undiagnosed hereditary hemochromatosis, transferrin saturation would be **high.**

Answer 95

Iron deficiency anemia (stage 3)

Answer 96

GI disease decreases absorption Polyphenols and oxalic acid in coffee decrease absorption Menstruation (iron loss in blood)

Answer 97

Take iron away from tums (at separate times) as the calcium in tums can decrease iron absorption.

Answer 98

Iron deficiency anemia

Answer 99

Answer → C

Answer 100

**Folate required for cell formation** Inadequate folate = impaired red blood cell synthesis = megaloblastic anemia Inadequate prenatal folate = improper closure of neural tube = neural tube defects

Answer 101

Folate functions interact with: * Vitamin B12 * Vitamin B6 * Riboflavin (FMN/FAD) * Choline

Answer 102

**MTHFR Gene encodes MTFHR protein (methylene THF reductase) → needed for regeneration of 5-methyl THF** **MTHFR 677C\>T variant** _Homozygous: 677TT_ * 30-35% remaining MTHFR activity * Elevated plasma homocysteine; impaired DNA methylation * Lower serum and RBC folate concentration * Increased risk of neural tube defects, CVD, some cancers, and neurological issues _Heterozygous: 677CT_ * 70% remaining MTHFR activity * Lower risk of diseases than 677TT

Answer 103

Folate coenzyme forms: * biologically active forms * interchangeable * substitutions at positions 5 & 10 * all reduced forms

Answer 104

* **Most common supplemental form** → folic acid * **Alternative supplemental form** → 5-MTHF, calcium salt * **Isolated form used as medication** → leucovorin (5-FTHF), also called folinic acid = medication used to decrease toxic effects of cancer drugs * **Form of natural food folate** = pteroyl**_poly_**glutamates (\>75%) in reduced forms (leafy greens, citrus, legumes) * **Most common form in fortified foods** = folic acid (**_mono_**glutamate) → fortification of wheat flour is mandatory by law in Canada → grain and bakery products

Answer 105

Folic acid or folates in monoglutamate form → no digestion required! Folate in polyglutamate form (most natural food folate) → digestion to monoglutamate form required **Process** → hydrolysis by folate hydrolase (**zinc dependent** brush border enzyme) Activity of folate hydrolase decreased by: * Zinc deficiency * Alcohol * Inhibitors in legumes, lentils, cabbage, and oranges

Answer 106

Monoglutamates do not need to be digested and thus are absorbed more readily.

Answer 107

1 mcg DFE = 1 mcg natural food folate; 0.6 mcg folic acid from fortified foods/supplements; 0.6 mcg supplemental folic acid on an empty stomach. The DFE takes into account that supplemental forms are absorbed more easily. This is because the folate is in the monoglutamate form and doesn't need to be digested.

Answer 108

* **Plasma/serum folate concentration** (fluctuates) * Short term indicator * Reflects acute folate intake * Sensitive to diurnal changes * **Red blood cell folate concentration** * folate incorporated in red blood cells during erythropoiesis; half-life of red blood cells is 60 days * Indicator of long-term folate status; preferred indicator for folate status

Answer 109

At risk populations with potentially increased requirement * Alcoholism (impaired digestion and absorption; malnutrition) * Gastrointestinal diseases like inflammatory bowel disease (malabsorption) * Individuals with *MTHFR 677TT genotype* * Gluten-free diet?

Answer 110

UL is specific to ‘folic acid’ → based on case reports that showed the **masking of hematological symptoms of vitamin B12 deficiency anemia** in patients who took 5mg folic acid per day.

Answer 111

* In addition to a healthy diet, people who could become pregnant should consume daily a 0.4mg folic acid supplement * High risk → personal or family history of NTD-affected pregnancy; epilepsy, obesity or poorly-controlled diabetes; *_may need more_* * Periconceptional folic acid supplements only taken by ~20% of women at child-bearing age due to low awareness and high number of unplanned pregnancies.

Answer 112

* Low folate intake/status has been associated with increased risk of **cardiovascular disease** and **dementia** → likely through roles involving elevated homocysteine * Low folate may increase risk of certain types of **cancer** → colon, lung, and GI cancers → impaired DNA/RNA methylation = altered gene expression/transcription → decreased thymidine synthesis leads to misincorporation of uracil for thymine in DNA → DNA strand breaks * But high folate intakes may increase cancer progression.

Answer 113

Any nutrient involved in generating S-Adenosyl-Methionine (SAM)

Answer 114

DNA methylation is an epigenetic modification to change expression of the DNA without changing the DNA sequence. Methylation prevents DNA from being expressed.

Answer 115

**Folate = transfer of methyl groups / one-carbon units** * Synthesis of purines & pyrimidines (nucleotides) → DNA formation * Regeneration of methionine = precursor for S-adenosylmethionine, a key methyl donor → DNA methylation and formation of neurotransmitters * Amino acid metabolism

Answer 116

Answer → A Folate would be trapped as 5-methyl THF

Answer 117

Answer → B Folic acid is a synthetic form found in supplements

Answer 118

_Folic acid_ * fully oxidized folate * ‘synthetic’ folate form * most stable folate forms used in vitamin supplements and fortifications.

Answer 119

1. glutamate: pteroylmonoglutamate 2. 8 glutamate residues: pteroylpolyglutamate

Answer 120

* In what form → Pteroylmonoglutamate forms * What site → duodenum, upper jejunum * How → at high intakes = passive diffusion; at low intakes = proton coupled folate transport (PCFT)

Answer 121

* After first pass through liver → folate is transported in circulation to all body tissues. * **Plasma/serum folate** * Main transport form = 5-MTHF; small amounts of monoglutamate forms * With folic acid intake \>200mcg, presence of unmetabolized folic acid in plasma * Monoglutamate forms for uptake of folate into the cells * Unbound or bound to proteins * **Cellular uptake into tissues/organs** * Monoglutamate forms only * Reduced folate carrier (main) * Major route of folate uptake * High affinity (5-MHTF), low affinity (folic acid)

Answer 122

Excreted in urine → intact folate and products of folate catabolism Some also secreted into bile → readsorption via enterohepatic circulation → minimal fecal excretion

Answer 123

Folic acid or folates in monoglutamate form → no digestion required! Folate in polyglutamate form (most natural food folate) → digestion to monoglutamate form required **Process** → hydrolysis by folate hydrolase (zinc dependent brush border enzyme) Activity of folate hydrolase decreased by: * Zinc deficiency * Alcohol * Inhibitors in legumes, lentils, cabbage, and oranges

Answer 124

Conversion of monoglutamate to polyglutamate forms by **folylpolyglutamate synthetase** which ‘traps’ folate in cells.

Answer 125

* Converted back to monoglutamate form, catalyzed by hydrolase * Transport out of enterocytes via multidrug resistant protein (MRP) * Hepatic portal vein → mainly in form of 5-MTHF and some 10-FTHF (all monoglutamate form); some folic acid (particularly at high intakes.

Answer 126

Answer → C

Answer 127

In cells → trapping of folate → conversion to polyglutamate forms Conversion of 5-MTHF (or folic acid) to THF = precursor for various coenzyme forms = storage form of folate in polyglutamate form Interconversion of folate forms (all in polyglutamate form) Glutamate residues need to be removed prior to folate release from cell

Answer 128

Answer → C

Answer 129

Macrocytic megaloblastic anemia

Answer 130

Nutritional folate deficiency ‘non-existant’ in Canadians → likely a result of mandatory food fortification with folic acid as well as high prevalence of vitamin supplement use in Canadians

Answer 131

DNA synthesis is impaired leading to defected erythrocyte division and maturation → **macrocytic, megaloblastic anemia**

Answer 132

Clinical sign → macrocytic (large) megaloblastic (immature and nucleated RBC in circulation) anemia

Answer 133

Answer → B

Answer 134

Neural tube defects (NTDs) RCTs showed: primary occurrence and re-occurrence of NTDs reduced in women who supplemented daily with folic acid.

Answer 135

Answer → B Folic acid fortification of flour has made a dramatic decrease in NTDs. This has been a very effective public health strategy.

Answer 136

High folic acid intake from prenatal supplements → folic acid intake from supplements in APrON study

Answer 137

Answer → D

Answer 138

* Do high folate/folic acid intake affect biological pathways leading to adverse health effects? * Does unmetabolized folic acid from high supplement intake adversely affect health?

Answer 139

Prevention of anemia Reducing risk of birth defects Reducing risk of chronic disease (CVD, cancer, dementia)

Answer 140

* Cobalamin is a water soluble vitamin containing cobalt. * -CN → Cyanocobalamin * -OH → Hydroxycobalamin * -H₂O → 5'-deoxyadenosylcobalamin\* * -CH₃ → Methylcobalamin\* * The starred two are the coenzyme forms of vitamin B12

Answer 141

1. Remethylation of homocysteine to methionine (cytosol) 1. Enzyme → methionine synthase 2. Coenzyme → **methylcobalamin** 2. Conversion of methylmalonyl-CoA to succinyl-CoA (mitochondria) 1. Enzyme → methylmalonyl-CoA mutase 2. Coenzyme → **5'-adenosylcobalamin**

Answer 142

* In vitamin B12 deficiency, remethylation of homocysteine to methionine is impaired; and thereby also formation of THF from 5-MTHF * Folate in form of 5-methyl THF is trapped * Formation of 5-MTHF is _irreversible_ * Reduced availability of folate forms for nucleotide formation and other functions. * Folic acid supplementation can overcome the ‘methyl-folate trap’ allowing DNA synthesis to occur.

Answer 143

* Naturally occurring in vitamin B12 is from microorganisms * Found only in animal source foods. * Animal products → **protein-bound** B12 → adenosylcobalamin, hydroxycobalamin, methylcobalamin * Supplements/fortified foods → **free/isolated B12** → hydroxycobalamin, cyanocobalamin, methylcobalamin

Answer 144

1. Pepsin/HCl in stomach release protein-bound B12 in food 2. **R proteins (haptocorrin)** from saliva and gastric juice bind to ‘free’ B12 3. Pancreatic proteases (pH\>7) release R protein 4. **IF** secreted from stomach (parietal cells) binds to B12 (duodenum) 5. Absorption: B12-IF receptor-mediated endocytosis 6. Absorption: passive diffusion (1-3%)

Answer 145

* In enterocyte → release of B12 from B12-IF-complex * Passage through basolateral membrane → through multidrug resistant proteins (MRP) * Transport via hepatic portal vein to liver → binding in blood to transcobalamin II (TCII) * Vitamin B12 in blood is bound to transporter proteins * TCII (transcobalamin) → 20% of circulating vitamin B12; half-life \<2 hours; carries newly absorbed vitamin B12 → available for receptor-mediated uptake into cells via TCII receptors * Haptocorrin (TCI) → 80% of circulating vitamin B12; half-life ~10 days

Answer 146

* Long-term storage, unlike other water-soluble vitamins, mainly in the form of adenosylcobalamin * Total body B12 → 2-3mg * Liver (~50%) * Muscle (~30%) * Other: pituitary gland, bone, kidneys, heart, brain and spleen * Adequate to prevent vitamin B12 deficiency for 3 - 5 years (assuming no further vitamin B12 intake).

Answer 147

**Enterohepatic circulation** 75% of vitamin B12 excreted in bile binds to IF in duodenum and reabsorbed in ileum → long biological half-life of B12. Not much metabolism occurs, B12 is either used as a coenzyme, recycled via enterohepatic circulation, or excreted in bile, urine, or through dermal loss.

Answer 148

* 0.1% (2mcg) of vitamin B12 excreted in **bile** * **Enterohepatic circulation** → 75% of vitamin B12 excreted in **bile** binds to IF in duodenum and **reabsorbed** in ileum → long biological half-life of B12 due to this recycling * 0.25mcg excreted in **urine** daily * Trace dermal losses

Answer 149

* Binds R protein in stomach, intrinsic factor in small intestine, and absorbed as a complex with intrinsic factor. * Large stores of B12 in liver and enterohepatic circulation = deficiency can take years.

Answer 150

**Mutation in TCII gene (TCN2)** Cytosine (C) is replaced by guanine (G) at base pair 776 (TC 776C G) * TCII reduced ability to bind and transport B12 to tissues * GG variant (homozygous) occurs in 20% of population → associated with (1) lower serum vitamin B12, (2) elevated plasma total homocysteine, and (3) psychiatric conditions

Answer 151

* **Low/no intake of animal source foods** → vegetarians/vegans (if no supplements / fortified foods) → B12 deficiency can take years to manifest due to B12 stores and enterohepatic circulation → *_deficiency more likely due to impaired absorption than inadequate intake_* * **Impaired vitamin B12 absorption** * **Medications** → H₂ blockers and proton pump inhibitors (decreased HCl production leads to increased gastric pH) → impairs digestion of food-bound vitamin B12 * **Diseases/conditions that cause malabsorption** → atrophic gastritis (chronic inflammation of gastric mucosa, occurs in 10-30% of elderly), pernicious anemia (autoimmune disorder that attacks parietal cells), individuals with stomach/small intestine resected, Celiac/Crohn's Disease (damage to absorptive surface).

Answer 152

**_Hematological symptoms_** * Megaloblastic macrocytic anemia (folate trapped as 5-MTHF) → fatigue, skin pallor, shortness of breath, palpitations * Decreased leukocyte and thrombocyte counts * Folic acid supplementation alone can overcome methyl folate trap and reverse hematological symptoms **_Neurological symptoms_ (unknown mechanism)** * Neuropathy = degeneration of the spinal cord by demyelination → poor coordination, numbness/pain in extremities, irritability, memory loss, hallucinations, psychosis, demention * Impaired child development

Answer 153

* 10-30% of older adults have atrophic gastritis and decreased stomach acidity, which can impair vitamin B12 absorption * For adults \>50 years, it is recommended that most of the RDA come from fortified foods or supplements, which are more readily absorbed since they are not food-bound.

Answer 154

_Total vitamin B12_ * Measures total circulating vitamin B12 bound to TCI, TCII, and TCIII. * Reflects both (1) intake and (2) status * Serum concentrations may be maintained at the expense of tissues → not a sensitive indicator of deficiency _Methylmalonic acid_ * Indicator of intracellular deficiency / metabolic insufficiency → functional indicator * Increased excretion in urine and increased serum concentration with B12 deficiency. _Total homocysteine_ * Indicator of intracellular deficiency / metabolic insufficiency → functional indicator * Increased excretion in urine and increased plasma concentration with deficiency of B12, folate, B6, B2 deficiency * Folate is the strongest determinant of plasma total homocysteine → indicator has low specificity for B12.

Answer 155

Answer → B Cyanocobalamin is not found in food, it is just found in supplement form.

Answer 156

* First, cobalamin bound to methionine synthase (MS) picks up a methyl group from 5-methyl THF producing THF and methylcobalamin. * Next, MS transfers the methyl group from methylcobalamin to homocysteine producing methionine and cobalamin. * Enzyme → methionine synthase (MS) * Coenzyme → methylcobalamin

Answer 157

Answer → D

Answer 158

* Enzyme → methylmalonyl-CoA mutase * Coenzyme → 5'-adenosylcobalamin * Propionyl-CoA arises from the oxidation of branched-chain amino acids and odd-chain fatty acids * Increased methylmalonic acid with vitamin B12 deficiency.

Answer 159

Answer → C

Answer 160

Answer → A

Answer 161

Based on the amount needed to maintain hematological status and normal serum vitamin B12 values (assuming 50% absorption rate). * 10-30% of older adults have atrophic gastritis and decreased stomach acidity, which can impair vitamin B12 absorption. * For adults \>50 years, it is recommended that most of the RDA come from fortified foods or supplements, since this B12 is in the free form and that is better absorbed by older adults.

Answer 162

Answer → D A is not correct because cyanocobalamin is a supplemental form that is not bound to proteins. B → vitamin B12 binds protein in the stomach C → IF is secreted from the stomach E → free vitamin B12 is taken up as a complex with IF

Answer 163

Answer → B * **Long-term storage,** unlike other water-soluble vitamins, mainly in the form of adenosylcobalamin * Total body B12 → 2-3mg * Liver (~50%) * Muscle (~30%) * Other: pituitary gland, bone, kidneys, heart, brain and spleen * Adequate to prevent vitamin B12 deficiency for 3 - 5 years (assuming no further vitamin B12 intake).

Answer 164

* **Adverse pregnancy outcomes** * Neural tube defects * Low birth weight * Intra-uterine growth restriction * Low infant B12 status → risk of cognitive impairment and poor child development; may be irreversible if treated too late * **Neurological symptoms** * Higher risk for cognitive impairment * More rapid cognitive decline * Increased rate of brain volume loss in elderly.

Answer 165

No tolerable upper intake level for vitamin B12. No toxicity or benefit reported from high doses of vitamin B12.

Answer 166

Answer → D High folic acid intake could make it harder to detect a B12 deficiency, but does not increase risk.

Answer 167

Answer → B MCV is a measure of the size of red blood cells. A microcytic anemia would produce a lower MCV.

Answer 168

Answer → D With both folate and B12 deficiency we can see increased homocystine (they are both involved in that pathway), as well as increased MCV. Increased methylmalonic acid is specific to B12.

Answer 169

Answer → D

Answer 170

* Choline is a tri-methylated compound that may be water-soluble or fat-soluble. * Choline in _natural food sources_: * Mostly (1) phosphatidylcholine * Some (2) sphingomyelin and (3) free choline * Choline in _supplements_: * (4) Choline chloride (free choline) * _Other_ sources * (5) Lecithin (= mixture of glycerophospholipids e.g., phosphatidycholine) often used as an emulsifier * Foods: * Beef * Egg * Soybeans * Shittake mushrooms

Answer 171

* Only needed for phosphatidylcholine (PC) * PC → lyso-PC + fatty acid (catalyzed by phospholipase A₂)

Answer 172

* Both free choline and lyso-PC * _Lyso-PC_ → absorbed with fat * Lyso-PC → absorbed in micelles via **passive diffusion** * PC incorporated into chylomicrons → enters lymph * _Free choline_ → absorbed as water-soluble. * Absorbed in the small intestine via a transporter (**facilitated diffusion**) * At high intakes, some absorption by **passive diffusion**. * If not absorbed, some degraded by gut bacteria to **betaine** and **TMA**.

Answer 173

* Lyso-PC → enters lymph → transported through body in lipoproteins * Free choline → From the enterocyte free choline enters the portal circulation → transported as free choline in blood → taken up by tissues via both diffusion and carrier mediated transport

Answer 174

Choline is oxidized to **betaine** in liver and kidney.

Answer 175

Excreted in urine, mainly as betaine. Betaine = osomoregulator; i.e., maintains osmotic pressure in kidneys.

Answer 176

* **Component of [4]**: * (1) Phosphatidylcholine and (2) sphingomyelin * Major phospholipids in cell membranes * PC needed for secretion of VLDL from liver * (3) Acetylcholine * Neurotransmitter important for memory and muscle control * (4) Platelet activating factor * Involved in blood clotting and inflammation * **Methyl donor** for homocysteine remethylation in one-carbon metabolism.

Answer 177

Three SAM groups are necessary for the de novo synthesis of choline. But we don't make enough.

Answer 178

* De novo synthesis rates are not adequate to meet the demand for the nutrient when the other nutrients are available in amounts sufficient to sustain normal growth and function. * Those who do not get enough choline in their diet exhibit liver damage.

Answer 179

* Plasma-free choline - most commonly used indicator of choline status * Not a reliable indicator for moderate changes in dietary intake, likely due to compensatory mechanisms. * No established cut-offs for plasma free choline concentrations to reflect choline status.

Answer 180

Amount of choline required depends on the other nutrients being consumed.

Answer 181

Some genetic variants may be associated with **higher requirements**, e.g., * ***MTHFR 677C\>T*** genetic variant influences need for choline. * MTHFR = 5,10-MTFH-reductase, forming 5-MTHF * ***MTR 2766A\>G*** * MTR = methionine synthase (B12 dependent enzyme), catalyzing homocysteine remethylation * When people have a polymorphism involved in these genes on the B12 side of the cycle, more choline will be required as a methyl donor.

Answer 182

* Deficiency in humans is rare. * Only documented in one study (Zeisel, 1991) and in patients receiving total parental nutrition (TPN) * Symptoms → liver damage; fatty liver (non-alcoholic, fatty liver disease)

Answer 183

* High doses of choline from supplements may lead to: * Fishy body odor due to bacterial metabolism of choline to trimethylamine mainly from free choline * Vomiting * Sweating * Salivation * Hypotension * Choline has a UL

Answer 184

Answer → C

Answer 185

Answer → E Component of acetylcholine. Component of phosphatidylcholine & sphingomyelin. Methylation Component of PAF All of the above basically.

Answer 186

* High choline intake during gestation and early post natal (animal models) * Improved cognition function in adulthood * Prevention of age-related memory decline * Protection of neuropathological changes associated with Alzheimer's Disease

Answer 187

* Choline can be **synthesized** if there are sufficient methyl nutrients. * The **need** for choline as a methyl donor is reduced with sufficient methyl nutrient intake. * Methyl nutrients that serve as methyl donors include: folate and B12, methionine, betaine * Dietary requirement for choline is dependent on the amount of methyl nutrients (folate and B12, Methionine and betaine) available in the body.

Answer 188

Answer → C

Answer 189

* Higher estrogen concentration during pregnancy promotes PEMT expression. * **Phosphatidylethanolamine N-methyltransferase (PEMT) is a transferase enzyme which converts phosphatidylethanolamine to phosphatidylcholine in the liver.** * Thus, estrogen results in increased choline de novo synthesis (i.e., choline may be more important during pregnancy) * Higher supplemental choline dose increases circulating maternal choline concentration in the 3rd trimester, however does not influence neonatal choline concentrations → studies with functional outcomes required. * Most women in Canada are not meeting the daily AI (450mg of choline) * Most women get their choline from dairy and eggs * Those in pregnancy doing better get 900mg (double the AI).

Answer 190

Answer → B This might change soon.

Answer 191

* Pregnancy * Dietary choline intake below AI for most pregnant people * Non-users of prenatal supplements (folic acid); those with low B12 status, and those with MTHFR 677TT genotype * People with certain genetic variants * SNPs for genes involved in the metabolism of choline, folate and methionine * Common SNP in the PEMT gene reduces endogenous synthesis of choline.

Answer 192

Answer → D

Answer 193

Answer → D

Answer 194

Pyrimidine ring attached to a thiazole ring by a methylene bridge, can exist as: Thiamin, free form Thiamin diphosphate (TDP) → a.k.a. thiamin pyrophosphate (TPP) = active form

Answer 195

**(1) TDP as coenzyme in major decarboxylation reactions of energy metabolism** → In thiamin deficiency, oxidation of glucose impaired with no alternative route **(2) thiamin has non-coenzyme function; nervous system function** → proposed role = influences nerve impulse transmission through maintenance of nerve membrane function and synthesis of myelin & neurotransmitters

Answer 196

* Mandatory fortification of thiamin → flour, white flour, enriched flour, meat analogues, liquid/frozen eggs * Foods of plant origin → free form (non-phosphorylated) * Foods of animal origin → thiamin diphosphate (TDP, 95%) thiamin mono-and tri-phosphate (TMP + TTP, 5%) * Supplements/fortified foods → free form (thiamin mononitrate or thiamin hydrochloride)

Answer 197

1. **Sensitive to sulfite** (from preservatives, dried fruit, wine, etc…) → sulfites attack the methylene bridge and break apart thiamine 2. **Heat destruction** 3. **Antithiamin factors** 1. _Thiaminases_ in raw fish and shellfish catalyze destruction of thiamin → cooking deactivates thiaminases 2. _Polyhydroxyphenols_ → tannic, chlorogenic, caffeic acid in coffee, tea, betel nuts, blueberries, red cabbage, etc… → inactivates thiamin by destruction of thiazole ring → thermostable → presence of vitamin C can prevent destruction

Answer 198

**Digestion required depends on the form** * **Free thiamin (plant forms)** → readily absorbed → no digestion required * **TMP, TDP, TTP (animal forms)** → require dephosphorylation; catalyzed by phosphatases in the small intestine

Answer 199

* Where: **duodenum** and **jejunum** are the main sites * How: in free form (non-phosphorylated) * **(1) active transport** through thiamin transporters ThTr1 and ThTr2; pH sensitive; saturation at \>5mg * **(2) passive diffusion** at intake levels \>2.5mg

Answer 200

Thiamin is distributed to tissues via the bloodstream. Uptake into cells → via active transport (ThTr1 and ThTr2) mostly by liver, skeletal muscle, and RBCs 90% of circulating thiamin is present in RBCs. Phosphorylation of thiamin upon cellular uptake

Answer 201

Total body thiamin stores ~25-30 mg Skeletal muscles contain about half of total body thiamin. Half-life of thiamin → ~9-20 days → depletion of body stores in 1-2 weeks to ~1 month.

Answer 202

* Thiamine is excreted through kidney → urinary excretion * Thiamin excreted intact or catabolized (cleaved and catabolized to \>20 metabolites).

Answer 203

* Rare in healthy individuals * In higher income countries, deficiency most common with: * **(1) Alcoholism** → decreased intake, absorption impaired, diminished utilization due to liver damage * **(2) Health conditions that lead to increased need** → cancer; HIV/AIDS; IBD; diuretics/dialysis; bariatric surgery * **(3) Diet of mainly raw seafood** → high in thiaminases * **(4) Chewing betel nuts** → high in polyhydroxyphenols * **(5) Mutation in gene encoding ThTr1** * In low-middle income countries deficiency is more common because lack of diverse food and reliance on low-thiamin staples (e.g., white rice)

Answer 204

Thiamin deficiency disease = Beriberi = ‘I cannot, I cannot’ Symptoms → anorexia, weight loss, profound weakness Severe cases → damage to neurological system & cardiovascular system; classified as dry, wet, or acute depending on conditions and symptoms; these conditions are not exclusive and someone with thiamine deficiency may experience symptoms of more than one type Also → Wernicke encephalopathy

Answer 205

* **(1) Erythrocyte transketolase activity coefficient (ETAC)** * The higher the activity increases, the lower the thiamin status * regarded as the _best functional indicator_ of biochemical thiamin status * Correlates poorly with dietary intake * The higher the ratio, the lower the thiamin status was, the more deficient the patient * **(2) Urinary thiamin excretion** * Affected by recent _dietary intake_ * Decreases with declining status * **(3) Total thiamin in whole blood and erythrocytes** * Thiamin in erythrocytes proportional to _tissue status_ * Does not reflect dietary intakes

Answer 206

Answer → D Glycolysis would predominate because entry of pyruvate into the TCA cycle would be inhibited; thus, lactic acid would build up.

Answer 207

Answer → D

Answer 208

Answer → D

Answer 209

Answer → C

Answer 210

**Neuromuscular beriberi** Characteristics: * Occurs in adults * Cause → chronic low thiamin intake → especially if coupled with high carb intake * Severe muscle weakness and wasting * Peripheral neuropathy → sensory and motor nerve conduction problems; mostly distal parts of the limbs (feet and hands)

Answer 211

**Edematous beriberi** Characteristics: * More extensive cardiovascular system damage → cardiomegaly (enlarged heart); tachycardia (rapid heartbeat); heart failure * Peripheral edema

Answer 212

**Infantile beriberi** Characteristics: * Occurs mostly in infants (e.g., breastfed by deficient mothers) * GI symptoms → anorexia, nausea, vomiting * Cardiovascular symptoms → rapid heartbeat, cardiomegaly * Lactic acidosis

Answer 213

* Symptoms: * Abnormal eye movement * Gait ataxia * Cognitive impairment * In severe form can include **Korsakoff psychosis** = amnesia, confusion, little/no working memory * In higher income countries, most common with chronic alcoholism

Answer 214

Non-protein, organic molecule that helps an enzyme function. Vitamins with coenzyme function → B vitamins!

Answer 215

False → no adverse effects from high dietary intakes of thiamin → no UL set.

Answer 216

True. No adverse effects from high dietary intakes of thiamin → no UL set.

Answer 217

**Active coenzyme form = pyridoxal phosphate (PLP)** 6 different vitamers → alcohol form, aldehyde form, and amine form → which can all be phosphorylated and/or interconverted

Answer 218

Chickpeas, bananas, watermelon, spinach, broccoli, zucchini, carrots, potato, pecans (liver, tuna, salmon, chicken, beef, pork) Main dietary source of B6 → PL, PLP, PM, PMP (meat and fish) Plant foods → PN, PNP *Note: refined flours are not a source.*

Answer 219

* Phosphorylated forms are dephosphorylated, by the enzymes: * Alkaline-phosphatase * Zinc-dependent * On the brush border * Non-specific phosphatases (GI tract)

Answer 220

* Free PN, PL, and PM are absorbed (mainly in jejunum) by **passive diffusion** * PNP, PLP, and PMP only absorbed at high intakes * Overall high absorption efficiency * No active transport for vitamin B6! * Some metabolic trapping of PN/PL/PM in enterocyte as phosphorylated forms * PN, PL, and PM cross basolateral membrane for entry into hepatic portal vein * Newly absorbed PL/PN/PM taken up by the liver through passive diffusion

Answer 221

**Systemic blood** → plasma/serum mainly in form of PLP and PL, bound to albumin **Tissue uptake** → non-phosphorylated B6 forms cross cell membranes; conversion of PLP to PL (by phosphatase) prior to uptake **Tissue distribution** → 75-80% of total body vitamin B6 in muscle, mostly in form of PLP bound to **glycogen phosphorylase**; 5-10% of total body vitamin B6 in liver

Answer 222

Vitamin B6 is a water-soluble vitamin with no appreciable stores in the body

Answer 223

PLP → PL → 4-pyridoxic acid (4-PA) * Liver metabolism → conversion of different forms in the liver; formation of PLP, the major coenzyme form, is **riboflavin dependent** * PL/PN/PM → PLP/PNP/PMP (ATP-dependent kinase) * PNP/PMP → PLP (FMN-dependent PNP and PMP oxidase; mainly found in liver and enterocytes) * PL and PLP → blood → extrahepatic tissues

Answer 224

* Mainly in form of 4-PA in the urine; some urinary excretion of PL * At high intakes of PN (through high-dose B6 supplements) excretion of B6 in form of PN and 5-pyridoxic acid; lower excretion of 4-PA

Answer 225

Vitamin B6, in form of PLP, functions as **coenzyme** in \>160 reactions, e.g.,: * Amino acid metabolism → transamination, dehydration, deamination, decarboxylation, transsulfuration * Production of neurotransmitters, nucleic acid, heme * Lipid metabolism → synthesis of sphingolipids; delta-6 desaturase (elongation and desaturation pathway); synthesis of carnitine (fatty acid oxidation) * Formation of niacin (vitamin B3) * Glycogen catabolism → **glycogen phosphorylase** (50% of body vitamin B6 used for this enzyme)

Answer 226

* **Cystathionine beta-synthase (CBS) deficiency** * 50% enzyme activity or less * Homocysteinuria (10-fold higher tHcy) * **High-dose of vitamin B6 supplements required;** dosage of 100-500mg; improves symptoms to some extent * Need to be monitored for toxicity effects. * CBS catalyzes the first step in the transsulfuration pathway → interdependent with folate cycle and methionine cycle * CBS deficiency means the body cannot process excess methionine/homocysteine. * **PLP = coenzyme in tryptophan-niacin pathway.** * Without B6 → xanthurenic acid excreted in urine (can use this as a measure of B6 status → introduce tryptophan load and monitor xanthurenic acid excretion in urine * **Niacin provides ADP-ribose units for proteins which are involved in DNA replication and repair**. * Non-coenzyme role: PLP affects **gene expression**

Answer 227

* **Folate (B9)** → PLP required for serine to glycine * **Riboflavin (B2)** → FMN required for PNP/PMP oxidation to PLP (conversion of different forms in the liver) * **Niacin (B3)** → PLP required for conversion of tryptophan to niacin * **Zinc** - alkaline phosphatase for digestion of PLP/PNP/PMP * Lipid metabolism * Protein intake & amino acid metabolism.

Answer 228

* **Direct methods (i.e., measurement of B6 markers)** * Plasma/serum PLP, PL, 4-PA * Urinary excretion of 4-PA and other B6 vitamers * **Indirect methods / functional biomarkers** * Erythrocyte transaminase activity * Tryptophan load test

Answer 229

* Low prevalence of clinical symptoms of vitamin B6 deficiency in humans → abundant occurrence of vitamin B6 in diverse food sources * Risk factors: * Alcoholism → impaired absorption * Drug-nutrient interactions: * Corticosteroids for suppressing immune system * Anticonvulsants for diminishing seizures

Answer 230

* **Dermatological signs** → seborrheic rash on the face, neck, and shoulders * **Neurological symptoms** → weakness, fatigue, confusion, peripheral neuropathy, seizures and convulsion * Reduced niacin synthesis from tryptophan * Hypochromic microcytic anemia due to reduced heme synthesis → the same outcome we see with an iron deficiency; hypochromic microcytic anemia could result from deficiency in either vitamin B6 or iron * Impaired one-carbon metabolism → elevated plasma total homocysteine (hyperhomocysteinemia) * Inflammation → due to elevated homocysteine or kynurenine which both have inflammatory properties

Answer 231

* Tingling in hands and feet = sensory and peripheral neuropathy (reversible to a point) * Impaired motor control at intake levels of \>2g/d * UL = 100 mg/day

Answer 232

Answer → D We only need ~1mg, not 100mg!

Answer 233

Answer → D Pyridoxal phosphate (PLP)

Answer 234

Answer → C Pyridoxine (PN) → supplement form

Answer 235

Answer → C This links B6 to the folate cycle and synthesis of nucleic acids.

Answer 236

Answer → D Niacin supplements are used for high cholesterol, not vitamin B6.

Answer 237

Answer → D

Answer 238

Answer → C Not necessary to supplement with B6 as it is absorbed and excreted efficiently, and it is abundant in many various food sources. Supplementation should be done under supervision to protect against toxicity.

Answer 239

**PLP = coenzyme in transamination reactions** Alanine aminotransferase (ALT) Aspartate aminotransferase (AST)

Answer 240

**PLP = coenzyme in decarboxylation reactions** * PLP as coenzyme for **histidine decarboxylase** → histidine to histamine (regulatory role in immune response) * Synthesis of **neurotransmitters** → glutamate to gamma-aminobutyric acid; 5-HTP to serotonin; L-DOPA to dopamine

Answer 241

**PLP = coenzyme in (side-chain) cleavage reactions** Shown: serine → glycine (important in interconversion of non-essential a.a.)

Answer 242

**PLP = coenzyme in transsulfuration pathway** *Transsulfuration = transfer of sulfur group from one amino acid to another; here: from homocysteine to serine forming cysteine* Build-up of homocysteine in the body is associated with many adverse outcomes. This transsulfuration pathway is one way to reduce homocysteine levels.

Answer 243

**Plasma PLP → a direct method** * Positive association between vitamin B6 intake and plasma PLP * Thought to reflect vitamin B6 **tissue stores (not much is stored, as B6 is a water-soluble vitamin)**

Answer 244

**24 hour urinary 4-pyridoxic acid (4-PA) → a direct method** * 40-60% of all vitamin B6 ingested is converted to 4-PA * Measured in 24 hour urine sample on several days for 1-3 weeks * Short term indicator * **≤3.0 µM/day** considered deficient

Answer 245

**Tryptophan load test** * The conversion of tryptophan to niacin is PLP dependent * Give 2g oral load of tryptophan * Measure xanthurenic acid excretion in urine * **\<65µmol/L** xanthurenic acid in urine is considered adequate

Answer 246

**Transaminase activity - indirect method** * Erythrocyte aspartic acid transferase and erythrocyte alanine transferase * The higher the activation coefficient, the lower the vitamin B6 status.

Answer 247

* CVD * Cognitive decline * Cancer * Mechanisms unclear, maybe: * One-carbon metabolism * Neurotransmitter formation * Lipid metabolism * Kynurenine pathway

Answer 248

Carpal tunnel Premenstrual syndrome (PMS) Morning sickness (nausea & vomiting of pregnancy) Depression

Answer 249

* First discovered in 1917 from milk whey * Water soluble * Yellow/orange solid * Light sensitive * Precursor for the coenzymes: * Flavin adenine dinucleotide (FAD) * Flavin mononucleotide (FMN)

Answer 250

* Dietary riboflavin → mostly FMN & FAD, some free riboflavin → sensitive to light * Mandatory fortification * White flour * Simulated meat products * Meal replacements * Voluntary fortification * Breakfast cereals * Dairy products; legumes

Answer 251

* Digestion is required! * Riboflavin, FMN, and FAD are non-covalently bound to proteins (e.g., albumin) * hydrochloric acid in the stomach and proteases from stomach, pancreas and small intestine separate the riboflavin from the protein * FMN and FAD need to be hydrolyzed to free riboflavin

Answer 252

* Where: upper small intestine * How: mostly as free riboflavin * (1) active transport through RFVT 3 * (2) passive diffusion at high-dose intake levels * Enters portal circulation mainly as free riboflavin but also as FMN

Answer 253

* Transported bound to proteins (e.g., **albumin**) * Free riboflavin is the form that enters the tissues and is converted to the coenzymes FMN and FAD in tissues.

Answer 254

* Larger amounts found *mainly* in the liver, heart, and kidneys. * Body stores estimated to last 2 - 6 weeks.

Answer 255

Free riboflavin is the form that enters tissues and is converted to coenzymes FMN and FAD in tissues.

Answer 256

* In the form of riboflavin in the urine. * Urine will become bright yellow if there is a lot of vitamin B2 (i.e., riboflavin) in the urine

Answer 257

* Non-specific symptoms, usually in combination with other nutrient deficiencies and can take months for them to appear. * Cheilosis → inflammation and cracking in the corner of the mouth * Glossitis → inflammation of the tongue

Answer 258

* (1) Excessive alcohol consumption → impairs absorption * (2) Photo-therapeutic treatment of **neonatal jaundice** → light destruction of riboflavin * _Aside_: Infant jaundice usually occurs because a baby's liver isn't mature enough to get rid of bilirubin in the bloodstream → the treatment helps to break it down so that the baby can excrete it * Bilirubin is a red-orange compound (hence the yellow colour of the baby - i.e., jaundice) that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the destruction of aged or abnormal red blood cells. * Some (3) disorders and (4) medications: * Diabetes → due to increased urine output * Methotrexate, tricyclic antidepressants

Answer 259

* **Urinary** **excretion of riboflavin** * Reflects _dietary intake when the tissues are saturated_ * Usually requires 24 hour urine collection * **Plasma riboflavin/FAD/FMN** * Reflects _recent dietary intake_ of riboflavin * Easy to obtain blood sample. * **Erythrocyte FAD/FMN** * Reflects _long-term intake_ * Easy to obtain blood sample * **Erythrocyte glutathione reductase activation coefficient (EGRAC)** * Reflects _long-term intake_ * Easy to obtain blood sample/longer to process * Gold standard for measuring riboflavin status

Answer 260

FMN and FAD function as **coenzymes** for many oxidation and reduction reactions (more than 100) including: * Energy metabolism * B6 metabolism * Fatty acid metabolism * Folate metabolism * Amino acid metabolism * GSSG to GSH (used to measure B2 status) * Synthesis of niacin from tryptophan * Protein folding * Neurotransmitters * Choline catabolism

Answer 261

* TCA cycle (succinate dehydrogenase, **FAD**) * Mitochondrial electron transport chain (**FMN & FAD**) * Beta oxidation (fatty acid oxidation) → acyl-CoA dehydrogenase (**FAD**)

Answer 262

* **Vitamin B6** → requires FMN to convert PNP and PMP to the coenzyme form pyridoxal 5'-phosphate (PLP) in the liver * The coenzyme forms of **niacin**, NAD and NADP, can be formed from tryptophan using FAD-dependent enzymes. * Iron and B6 are also involved in this pathway. * Riboflavin deficiency impairs internal iron utilization e.g., **release of iron from stores**. It thereby impacts red blood cell formation. Riboflavin deficiency may accelerate iron deficiency anemia. * **Methyl nutrients** → in one-carbon metabolism, the B-vitamins: ***folate, B12, choline, B6, and riboflavin have interdependent roles.***

Answer 263

* **MTHFR C677T**: a common mutation in the methylenetetrahydrofolate reductase gene * ~10% of Canadians are homozygous (TT) for this genetic variant. * MTHFR requires FAD as a cofactor * FAD falls off more readily in individuals with the homozygous genotype. * Thus, the enzyme has reduced activity.

Answer 264

Answer → D Riboflavin must be released from proteins (via acidic environment of the stomach and proteases). Elders generally have a lower stomach acidity (i.e., atrophic gastritis) so they have reduced digestion (and thereby reduced absorption). Diabetics urinate more frequently, so their riboflavin excretions are elevated. Diabetes can be a risk factor for most water-soluble vitamins (i.e., readily excreted in urine).

Answer 265

Answer → A B is not as likely, multiple studies have same intake results. C is not likely → no indication to suggest riboflavin is not bioavailable → we absorb most dietary riboflavin

Answer 266

Answer → E

Answer 267

* Riboflavin * Flavin mononucleotide (FMN) * Flavin adenine dinucleotide (FAD) * FMN and FAD are the metabolically active forms of riboflavin * Coenzymes in over 100 reactions in the body.

Answer 268

* Prevalence of suboptimal status may be higher than currently estimated. * Because of lack of a convenient biomarker, most countries have no nationwide data on riboflavin status (only intake) * Implications of suboptimal status are unclear but have been associated with: * Anemia * Hypertension * Pre-eclampsia in pregnancy * Possibly increased risk of CVD and cancer

Answer 269

* Urinary riboflavin inflection point used to estimate requirement in adults * The sharp rise in the curve occurs when the tissues are saturated and riboflavin is excreted * ~1.13 mg/day * HOWEVER → when using a functional marker instead of the urinary excretion marker, greater intake is necessary (i.e., the EAR is set too low)

Answer 270

False. Plasma riboflavin/FMN/FAD reflects recent dietary intake of riboflavin.

Answer 271

False. It reflects dietary intake when tissues are saturated.

Answer 272

**Erythrocyte glutathione reductase activation coefficient** * Measures the FAD dependent enzyme erythrocyte glutathione reductase

Answer 273

* International Research collaboration between Canada, Ireland, and the UK to develop *accessible* **blood indicators for vitamin B2 status assessment** and identify which most sensitively reflect dietary intakes and food sources of vitamin B2 in Irish and Canadian adults

Answer 274

Reduction of oxidized form of glutathione GSSG (oxidized form) to reduced form of glutathione (GSH) → an important antioxidant in the body

Answer 275

The formation of **PLP** (the major coenzyme form of vitamin B6) in the liver, is **riboflavin dependent**.

Answer 276

FAD is needed for synthesis of niacin (NAD) from tryptophan.

Answer 277

Answer → B

Answer 278

* Genetic studies report that *MTHFR* relates to variability in blood pressure * High blood pressure → the leading cause of preventable, premature death; major risk factor for CVD * Riboflavin supplementation may help to reduce high blood pressure in those with the homozygous variant. * This has been shown in a few studies (see slides, not shown here).

Answer 279

* Weight loss * **Riboflavin (genotype-specific) → effects are comparable to other things in this list that we tell people to do for hypertension** * Physical activity * Sodium reduction * Limit alcohol

Answer 280

False. No UL for riboflavin! Only reported side effect of high intake levels → bright yellow urine

Answer 281

True. No UL for riboflavin! Only reported side effect of high intake levels → bright yellow urine

Answer 282

More research is needed to: * **Develop biomarkers** to assess the prevalence of riboflavin deficiency/suboptimal status across populations. * **Determine health implications** of suboptimal status.

Answer 283

Answer → C ## Footnote **Personalized nutrition approach**

Answer 284

An essential component of four biotin-dependent carboxylases: 1. **Pyruvate carboxylase** in gluconeogenesis 2. **Acetyl CoA carboxylase** in fatty acid synthesis 3. **Propionyl CoA carboxylase** in odd chain fatty acid and amino acid metabolism 4. **Beta-methylcrotonyl CoA carboxylase** in leucine catabolism Apocarboxylase = carboxylase without biotin Holocarboxylase = carboxylase with biotin

Answer 285

**Forms of biotin found in foods**: * Free biotin * Biotin bound to protein * Some cannot be digested (Biotin bound to avidin in egg whites) * Most protein bound biotin digested to * **Biocytin** = biotin bound to lysine, which is digested by **biotinidases** in the small intestine.

Answer 286

* Most protein bound biotin is digested to **biocytin** (= biotin bound to lysine) which is digested by **biotidinases** in the small intestine.

Answer 287

* **Neurological symptoms** → lethargy; paresthesia, hypotonia, depression, hallucinations * **Dermatological symptoms** → red, dry, scaly dermatitis around eyes, nose, mouth * **Other symptoms** → anorexia, body hair loss, brittle nails

Answer 288

NAD⁺ → nicotinamide adenine dinucleotide NADP⁺ → nicotinamide adenine dinucleotide phosphate

Answer 289

Requirements are expressed in units of niacin equivalent (NE) → unit used to express niacin content of food → **1 mg NE = 1 mg niacin or 60 mg tryptophan** **NE** represents niacin in the diet + niacin converted from tryptophan in the diet **NAD** synthesis from tryptophan in the liver ~60 mg of dietary tryptophan = 1 mg niacin Importance of tryptophan in meeting niacin requirements reflected in **Hartnup Disease** (autosomal recessive disorder that interferes with the absorption of tryptophan in the intestine and kidney)

Answer 290

Coenzyme role In their coenzyme role, NADH and NADPH act as hydrogen donors (NADH, NADPH) or electron acceptors (NAD⁺, NADP⁺)

Answer 291

* **Nicotinic acid for reducing cholesterol** * Doses of up to 6g/day * Reduce secretion of VLDL (and therefore LDL) likely through processes involving G protein activity * Concern for both efficacy and safety * **Nicotinamide for skin** * Used topically for inflammation associated with acne * May also be used for other skin conditions.

Answer 292

* **Niacin deficiency disease = pellagra** * Major epidemic in southern US states around 1905; corn as major staples * Corn/maise contains non-bioavailable forms of niacin (niacytin and niacinogen); released when treated with baess, e.g., lime water as used by indigenous cultures of the Americas

Answer 293

* Pantothenic acid is a component of: * Coenzyme A * Acyl carrier protein

Answer 294

* Forms of pantothenic acid in foods * CoA (85%; main form) * Free pantothenic acid * Acyl carrier protein * Supplemental form * Calcium pantothenate * Liver is a rich source of pantothenic acid; avocado is a good plant-based source

Answer 295

Deficiency is rare in humans → may occur in conjunction with multiple nutrient deficiencies (severe malnutrition)

Answer 296

* Burning feet syndrome * Numbness of toes * Burning sensation and redness in the feet * Also known as nutritional erythromelalgia

Answer 297

Answer → A Biotin is bound to avidin in egg whites.

Answer 298

* **Nutritional deficiency very rare in humans** → may occur in conjunction with multiple nutrient deficiencies (severe malnutrition) * **Risk factors/causes for biotin deficiency**: * (1) Excessive ingestion of raw egg whites * (2) Genetic defects involving biotinidase or holocarboxylase synthetase * (3) Alcoholism * Certain (4) conditions and (5) medications * Gastrointestinal disorders (IBD) * Anticonvulsant drugs

Answer 299

Answer → C Biotin deficiency is rare.

Answer 300

* Biotin deficiency can lead to hair loss, skin rashes, and brittle nails. * Supplements have been promoted for hair, skin & nail health * Do they work? * Possibly, but only if you are deficient in biotin * Very little evidence to support using biotin for hair, skin, & nail growth in healthy individuals

Answer 301

* Insufficient evidence to derive estimated average requirement values. * **AI values** for all population groups * **No UL for biotin.**

Answer 302

False. No UL for biotin.

Answer 303

* **Plants** → nicotinic acid; less bioavailable forms: niacytin (= bound to carbohydrate), niacinogens (= bound to protein) * **Animal sources** → nicotinamide, NADH, NADPH * **Food fortification** → flour is fortified by law in Canada → niacin or niacinamide * Good sources include → peanut butter and lentils

Answer 304

Precursor = tryptophan Pathway depends on: * Riboflavin (as FAD) * Vitamin B6 (as PLP) * Iron

Answer 305

Answer → D Abundant in meats, legumes, enriched and whole grains, tryptophan (= not lacking in diet)

Answer 306

Answer → C NAD⁺ (ready for oxidation reactions) → can accept protons and become NADH in oxidation reactions NADPH (in reduced form and ready for biosynthetic reactions)

Answer 307

**Oxidation of fuel molecules** * Glycolysis (glyceraldehyde-3-phosphate dehydrogenase) * Pyruvate dehydrogenase (pyruvate → acetyl-CoA) * Beta oxidation of fatty acids * TCA cycle (oxidation of acetyl-CoA) * Oxidation of ethanol (alcohol dehydrogenase) * NADH then transferred to electron transport chain for formation of ATP

Answer 308

* **Biosynthetic processes** * Fatty acid synthesis * Cholesterol and steroid hormone synthesis * Deoxyribonucleotide (precursor of DNA) synthesis * Glutathione (GSH) and vitamin C regeneration * Folate coenzyme synthesis

Answer 309

Jerome would be at risk of biotin deficiency. Some protein-bound biotin cannot be digested (e.g.., Biotin bound to avidin in egg whites). Symptoms of a biotin deficiency: * **Neurological symptoms** → lethargy; paresthesia, hypotonia, depression, hallucinations * **Dermatological symptoms** → red, dry, scaly dermatitis around eyes, nose, mouth * **Other symptoms** → anorexia, body hair loss, brittle nails

Answer 310

This will increase her needs for biotin. Biotidinase is needed for the digestion of biotin, so that we can absorb it, and also so that we can recycle it in the body. Holocarboxylase synthase is needed to attach biotin to carboxylases, so if this is not happening, then the carboxylases will not be working efficiently. She will be at increased risk of biotin deficiency.

Answer 311

Unless she is deficient in biotin they will likely not do anything. If she is getting enough biotin in her diet she will likely not notice any improvement. However, there is no UL for biotin, so if she wants to take a supplement, there is no harm in doing so.

Answer 312

We can get niacin from both niacin and tryptophan, so NE takes into account endogenous synthesis of niacin from tryptophan as well.

Answer 313

They ate corn/maize as a staple which has a non-bioavailable form of niocin (niocytin and niocynogen). Corn/maize contains non-bioavailable forms of niacin (niacytin and niacinogen); released when treated with bases, e.g., lime water as used by indigenous cultures of the Americas.

Answer 314

Reducing cholesterol, or used topically skin conditions. * Signs/symptoms of excess intake: * Flushing * Nausea * Liver damage * Impaired glucose tolerance (chronic excess) * **UL for adults 19 years and older: 35 mg/day from supplements and fortified foods** * (UL not meant to apply to individuals who are receiving niacin under medical supervision)*

Answer 315

Pantothenic acid is a component of coenzyme-A, which is important in energy metabolism. Diana is probably not low in pantothenic acid. **Nutritional deficiency of pantothenic acid very rare in humans;** may occur in conjunction with multiple nutrient deficiencies (i.e., severe malnutrition)

Answer 316

NADPH → formation for biosynthetic processes

Answer 317

Niacin deficiency disease * Dermatitis * Dementia * Diarrhea * Death There is little storage of niacin → early features of pellagra can occur after 45 days of depletion

Answer 318

* Flushing * Nausea * Liver damage * Impaired glucose tolerance * *UL for adults 19 years and older → 35mg/day from supplements and fortified foods*

Answer 319

False. ## Footnote **→ UL for adults 19 years and older: supplements and fortified foods → 35 mg/day of niacin from**

Answer 320

True. **→ UL for adults 19 years and older: supplements and fortified foods → 35 mg/day of niacin from**

Answer 321

Answer → C For each 60g of tryptophan = 1 NE

Answer 322

Answer → B UL for niacin is 35 mg/day; you ate 39 NE → but the UL is specifically 35 mg/day of niacin from supplements and fortified foods.

Answer 323

* Pantothenic acid is a component of CoA; biochemical roles: * **Oxidation of fuel molecules to energy** → glucose, fatty acids, amino acids * **Synthesis of lipids** → fatty acids, triglycerides, cholesterol, ketone bodies, phospholipids * **Acylation of proteins**

Answer 324

Answer → A

Answer 325

Acyl carrier protein is a component of fatty acid synthase complex which catalyzes the chain of elongation during fatty acid synthesis. Pantothenic acid is a component of acyl carrier protein.

Answer 326

* Insufficient evidence to derive estimated average requirement values → **AI values for all population groups**

Answer 327

False. Pantothenic acid has AI values for all population groups.

Answer 328

Answer → C

Answer 329

Folic acid Riboflavin Iron Niacin Thiamin ‘FRINT’

Answer 330

Answer → D

Answer 331

Answer → B

Answer 332

Answer → B

Answer 333

Vitamin B12

Answer 334

Answer → C

Answer 335

Answer → C

Answer 336

Iron is absorbed mainly as heme iron and as [Fe²⁺]. Iron is transported bound to transferrin as [Fe³⁺] and stored bound to ferritin as [Fe³⁺].

Answer 337

Answer → C

Answer 338

Answer → B

Answer 339

Answer → C

Answer 340

Answer → C

Answer 341

Answer → B

Answer 342

Answer → D

Answer 343

Answer → A

Answer 344

Answer → C

Answer 345

Answer → E

Answer 346

Answer → E

Answer 347

Vitamin B12

Answer 348

Answer → D

Answer 349

Answer → A

Answer 350

Answer → B

Answer 351

Answer → E

Answer 352

Answer → D

Answer 353

Answer → C

Answer 354

Answer → B

Answer 355

Evidence for choline needs comes mostly from a single study done in men and there was insufficient evidence to establish an EAR.

Answer 356

Non-alcoholic fatty liver disease and liver damage

Answer 357

Fishy body odour Vomiting Sweating Salivation Hypotension

Answer 358

Eggs Peanuts Beef

Answer 359

* In this method, the activity of an enzyme is first measured without added coenzyme. Then, excess coenzyme is added and the activity is measured again. The ratio of the activity with added coenzyme/activity without coenzyme is determined. If coenzyme status is adequate, adding more coenzyme will not increase enzyme activity and the ratio will be close to 1. If, however, coenzyme status was low/deficient, adding more coenzyme will lead to an increase in activity and the ratio will be greater than 1. * For example, this is used to assess riboflavin status by measuring activity of erythrocyte glutathione reductase. The activity of this enzyme is measured with and without added riboflavin and the coefficient of activity is determined as the activity of the enzyme with/without the coenzyme. If the ratio is close to 1, this means that riboflavin status was adequate - in other words, extra riboflavin was not needed to maximize the activity of the enzyme. If the ratio is much greater than 1, this means that riboflavin status in the body was not adequate, as extra riboflavin was needed to maximize enzyme activity. *

Answer 360

1878 mcg DFE Sally should be taking 400mcg folate not 1000mcg per day, unless a medical reason exists for doing so. Her folic acid levels would be high because she is eating much more than the recommended intake for folic acid from her supplement and fortified foods. The body absorbs both folic acid and reduced folates from the diet. Most of the folic acid is reduced to folate, but if folic acid intakes are high, some folic acid remains in the oxidized form and would be present in the blood plasma. Adding to this, cells preferentially take up reduced folates, leaving excess folic acid in the circulation.

Answer 361

Choline Biotin Pantothenic acid Vitamin K

Answer 362

Iron Thiamin (B1) Riboflavin (B2) Niacin (B3) B6 Folate (B9) B12

Answer 363

**Niacin (B3)** → flushing, nausea, liver damage, impaired glucose tolerance **B6** → sensory and peripheral neuropathy **Folic acid →** masks hematological symptoms of B12 deficiency **Iron** → iron overload **Choline →** fishy body odour, vomiting, sweating, salivation

Answer 364

Thiamin (B1) Riboflavin (B2) Pantothenic acid (B5) Biotin (B7) B12 Vitamin K