Midterm 1 Material

Question 1

Define the terms nutrient, essential nutrient & micronutrient.

Answer 1

Nutrient: substance obtained from food that is necessary for normal growth and development, and the maintenance of health.

Essential Nutrient: either not synthesized by the human body, or not synthesized in adequate amounts, and must be obtained from the diet.

Micronutrients: essential nutrients that are required in small amounts for normal growth, development and maintenance of health of living organisms. Micronutrients do not provide energy.

Question 2

Define vitamin & mineral.

Answer 2

Vitamin: miscellaneous group of structurally and functionally unrelated organic compounds required in the diet in small amounts for normal growth, development, and maintenance of health of living organisms. Vitamins do not provide energy.

• Organic compounds contain carbon atoms and covalent bonds, and they are degradable by oxidation (e.g., vitamin C, folate), heat (e.g., thiamin/B1, pantothenic acid), and UV light (e.g., riboflavin/B2)

Mineral: in nutrition, a ‘mineral’ refers to any element other than carbon (C), oxygen (O), hydrogen (H), or nitrogen (N); inorganic material; majority of elements in the periodic table exist in the human body; ‘minerals’ and ‘elements’ used interchangeably in nutrition

Question 3

List the fat soluble and water soluble vitamins.

Answer 3

Fat soluble: A, D, E, K

Water soluble: all others

Question 4

Describe the biological significance of vitamin solubility. [5]

Answer 4

• Differences in (1) absorption, (2) transport, (3) storage, (4) excretion & (5) toxicity

Water-soluble vitamins

• Absorbed directly into the bloodstream; travel via hepatic portal vein to liver after absorption
• Some travel unbound in the blood.
• Little storage; require continuous intake
• Excreted in urine
• Less likely to cause toxicity

Fat-soluble vitamins

• Absorbed with lipids in chylomicrons, enter lymph that drains into bloodstream via thoracic duct.
• Bound to proteins in blood circulation
• Some storage in body typically in the liver and adipose tissue
• Generally not excreted in the urine, typically excreted with bile in feces.
• Excessive intake can lead to adverse health outcomes

Question 5

Differentiate between essential and non-essential minerals.

Answer 5

• Minerals classified by level of requirements:
  
  • Macromineral: required in amounts >100mg/day
  • Trace minerals: required in amounts <100 mg/day
  • Ultratrace element: required in amounts <1mg/day
• Minerals may also be classified based on whether or not it has functions in the body:
  
  • Essential minerals: required in the body; must be obtained from the diet; when absent from diet deficiency symptoms result.
  • Potentially essential: may have functions in the body; however, not yet established as essential.
  • Non-essential minerals: no known function in the body; consumption may lead to toxic effects

Question 6

Comment on the potential toxicity of minerals.

Answer 6

• Both essential and non-essential minerals are toxic at some level
  
  • Of particular concern, minerals with a very narrow range of safe intake levels.

Question 7

Which vitamins have a faster turnover rate in the body?

Answer 7

Vitamin C and B1

(water-soluble vitamins have a faster turnover than fat-soluble vitamins)

Question 8

Define digestion.

Answer 8

Digestion refers to the chemical and mechanical processes that break foods into units that can be absorbed.

Mechanical processes are those that physically break food into smaller pieces (e.g., chewing in the mouth, grinding in the stomach).

Chemical processes include actions of secretions, and enzyme assisted hydrolysis reactions that break larger nutrients into smaller compounds. (e.g., hydrolysis of starch into glucose).

Question 9

Define absorption.

Answer 9

The process by which digested food particles are taken up through the small intestine for transport through the body.

Question 10

What do the processes of digestion and absorption require?

Answer 10

Muscle action

Enzymes

Hormones

Neural activity

Question 11

Define ‘gastrointestinal tract’ and list the major organs and accessory organs of the digestive system.

Answer 11

• The GI tract is the muscular tube extending from the mouth to anus, through which food passes to be (1) digested, (2) absorbed, and (3) excreted.
• Food passes through each of the major organs as it travels through the digestive system.
  
  • These organs include [5] → the mouth, esophagus, stomach, small intestine, large intestine.
• Accessory organs assist in the digestion and absorption process but do not directly come into contact with food.
  
  • Accessory organs of the digestive system include [4] the salivary glands, pancreas, liver, and gall bladder.

Question 12

Trace the pathway of food: what happens in the mouth?

Answer 12

• Major actions → food is broken down into smaller pieces and mixed with fluid so it can be swallowed.
• Teeth → physically break down food into smaller pieces via mastication
• Tongue: moves food around to facilitate chewing and swallowing; tastes food
  
  • Taste sensations → sweet, sour, bitter, salty, and umami; only particles in solution can react with taste buds.
  • The unique tastes of foods are a combination of the 5 primary tastes, plus olfaction (smell) and texture.
• Foods are blended with fluid from foods, beverages, and salivary glands to ease swallowing.
• Salivary glands → secrete saliva
• The swallowed food is called a bolus → from the mouth the bolus enters the pharynx and then the esophagus. Closing of the epiglottis ensures food enters the esophagus, not the lungs.

Question 13

What does saliva contain? What does it do?

Answer 13

Saliva contains [4] water, mucus, salts, and salivary amylase, an enzyme that digests carbohydrate.

Saliva helps (1) moisten foods for swallowing, (2) begins digestion of carbohydrates via salivary amylase, and (3) protects mouth and teeth from damaging substances.

Question 14

Trace the path of food: what happens in the esophagus?

Answer 14

• Major actions: Food passes from mouth to stomach.
• Food moves via peristalsis (wavelike contractions of the GI tract)
• The upper esophageal sphincter permits passage of food from mouth to esophagus, and prevents passage of food back to the mouth.
• The lower esophageal sphincter permits passage of food from esophagus to stomach, and prevents passage back to the esophagus.

Question 15

Trace the path of food: what happens in the stomach?

Answer 15

• Major actions: mixing, grinding, and digestion of food into chyme, using acid and enzymes.
• Gastric glands secrete gastric juice, a mixture of water, hydrochloric acid, and acid-stable enzymes.
• The low pH of gastric juice destroys most bacteria and denatures proteins.
• Physical digestion occurs through the grinding and churning of the strong muscles of the stomach.
• Chemical digestion of proteins (and some fat) is accomplished through enzymes in gastric juice. The acidity of the gastric juice denatures salivary amylase, therefore, there is very little carbohydrate digestion in the stomach.
• Chyme (food particles suspended in fluid) is released in small amounts via the pyloric sphincter.

Question 16

Trace the path of food: what happens in the small intestine?

Answer 16

• Major actions: enzymatic digestion of foods, absorption of nutrients
• Anatomy: the three sections of the small intestine in order are the duodenum, jejunum, and ileum.
• Most digestion and absorption of food occurs in the small intestine.
• Chyme from the stomach is slowly released into the small intestine and mixes with intestinal juices, pancreatic juices, and bile.
• In the intestine, chyme is mixed with secretions from the intestine, pancreas, and gallbladder:
  
  • Crypt glands in the intestine secrete intestinal juices which contain water and intestinal enzymes that digest carbohydrate and protein.
  • The pancreas secretes pancreatic juices which travel to the small intestine via the pancreatic duct. Pancreatic juices contain enzymes that digest protein, carbohydrate, and fat, and bicarbonate that neutralizes the acidic pH of chyme from the stomach.
  • Bile is synthesized in the liver and stored in the gallbladder until needed. The gallbladder secretes bile to the small intestine via the bile duct. Bile emulsifies fat so it can be digested and absorbed.
• The surface area of the small intestine is increased by the presence of folds and projections (villi). Villi are made of absorptive cells (enterocytes) surrounding a network of blood capillaries and a lacteal (lymphatic vessel). The absorptive cells also have projections called microvilli that increase the surface area available for absorption. The microvilli resemble bristle on a brush and, so this is termed the ‘brush border’ membrane.
• Nutrients are absorbed into the small intestine cells via passive, facilitated, or active transport.
• The remaining unabsorbed food travels to the large intestine via the ileocecal sphincter.

Question 17

Trace the path of food: what occurs in the large intestine?

Answer 17

• Major actions: absorption of water; excretion of waste (feces)
• Unabsorbed food (including undigested fibers) travels through the ascending, transverse, and descending colon to the rectum. The large intestine holds the unabsorbed food, absorbs water, and some nutrients from it, and leaves a semi-solid waste (feces) to be excreted.
• Bacterial fermentation of undigested material produces short chain fatty acids and gases.
• Waste is excreted via the rectal sphincter (under involuntary control) and the anal sphincter (under voluntary control).

Question 18

What is transit time, and what effects it?

Answer 18

• A meal can take about 6 - 10 hours to be digested and absorbed, and even longer (12 - 24 hours or more) to pass through the large intestine. The time it takes for food to pass from the mouth to anus is termed the transit time.
• Many factors influence the time needed for digestion and absorption, including the health of the GI tract, fiber content of the food, the size and composition of the meal.

Question 19

Discuss the general mechanisms by which nutrients are absorbed.

Answer 19

• Nutrients are absorbed into the small intestine cells via passive, facilitated, or active transport.
• Passive diffusion → involves a nutrient passing through the intestinal cell plasma membrane down its concentration gradient
• Facilitated diffusion → involves a transport protein that assists in moving the nutrient across the plasma membrane
• Active transport involves the use of energy and transport proteins to transport a nutrient against its concentration gradient
• Nutrients that pass from the lumen of the small intestine, across the brush border membrane and into the enterocyte (absorptive cell), and then across the basolateral membrane to exit the enterocyte and then enter the blood or lymph

Question 20

Discuss nutrient transport through the blood and lymph.

Answer 20

• Once nutrients exit the absorptive cells (villi), they enter one of two systems: blood or lymph.
• Proteins, carbohydrates, water-soluble vitamins, minerals, and some small lipids are absorbed directly into the bloodstream via capillary beds in the villi. Blood from these capillaries collects in a large vein called the hepatic portal vein, which leads directly to the liver.
• The liver is the first organ to receive nutrients absorbed into the blood. It acts as a gatekeeper to detoxify foreign or toxic substances (e.g., alcohol, drugs, poisons). Blood leaves the liver by the hepatic vein, which circulates to the heart and then the rest of the body.
• Fat soluble vitamins and larger lipids form chylomicrons (a type of lipoprotein) in the enterocyte and then enter the lymphatic system. Nutrients travel in the lymphatic vessels to the thoracic duct where they drain into the blood at the subclavian vein, and then circulate to the rest of the body.

Question 21

Discuss the role of hormones and the nervous system in regulation of digestion and absorption.

Answer 21

• A hormone is a substance that is produced at one site in the body in response to a particular stimulus, travels through the blood stream to a different site (i.e., target organ) and elicits a response there.
• Hormones help to maintain homeostasis (the maintenance of stable internal conditions) in the GI tract, by stimulating and shutting off digestive secretions
• Hormones important in digestion and absorption include: gastrin, secretin, and cholecytoskinin.
• The nervous system senses the contents (nutrients, chemicals, pH) of the GI tract, and stretching of the organs of the GI tract. It interprets these sensations, and then sends impulses to the smooth muscle lining of the GI tract to stimulate movement. It also stimulates secretions from glands of the GI tract. The part of the nervous system that controls the GI tract is known as the enteric nervous system.

Question 22

What are DRI?

Answer 22

Nutrient recommendations developed jointly by the US Food and Nutrition Board and Health Canada. The DRI were established by nutrition experts and are based on the best available scientific evidence. The DRI provide average daily nutrient intake recommendations for healthy individuals, and are divided into multiple life stage (age) and gender groups.

The DRI for most nutrients consists of four reference values: EAR, RDA, AI and UI.

Question 23

Define EAR.

Answer 23

Estimated average requirement

Daily intake level that is estimated to meet the nutrient requirement of half the healthy individuals in a particular life stage and gender group.

Note: ‘requirement’ refers to the amount of a nutrient needed in the diet; established for each nutrient based on different criteria (e.g., requirement for vitamin D is based on the amount needed for optimal bone health)

Question 24

Define RDA.

Answer 24

Recommended dietary allowance

Daily intake level that is estimated to meet the nutrient requirement of nearly all (97 to 98 %) healthy individuals in a particular life stage and gender group.

The RDA is mathematically derived from the EAR. Individuals should aim to meet the RDA for a nutrient.

Question 25

Define AI.

Answer 25

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).

Question 26

Define AI.

Answer 26

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).

Question 27

Define UL.

Answer 27

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.

Question 28

What can the DRI be used for?

Answer 28

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.

Question 29

Define EER.

Answer 29

Estimated energy requirement

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

Question 30

Define AMDR.

Answer 30

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%

Question 31

What is vitamin K? List the forms of vitamin K.

Answer 31

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.

Question 32

Provide examples of dietary sources for vitamin K.

Answer 32

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)

Question 33

Explain the processes and sites of vitamin K digestion.

Answer 33

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

Question 34

Explain the processes and sites of vitamin K absorption.

Answer 34

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.

Question 35

Explain the processes and sites of vitamin K transport.

Answer 35

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.

Question 36

Explain the processes and sites of vitamin K storage.

Answer 36

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.

Question 37

Explain the processes and sites of vitamin K metabolism.

Answer 37

Phylloquinone: almost completely metabolized; oxidation of side chain and conjugation with glucuronic acid

Menaquinone: little is known

Question 38

Explain the processes and sites of vitamin K excretion.

Answer 38

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

Question 39

Describe the biochemical role and physiological functions of vitamin K.

Answer 39

• 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.

Question 40

Explain the interaction between vitamin K and anti-coagulants.

Answer 40

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.

Question 41

Discuss the physiological implications of vitamin K deficiency and suboptimal status.

Answer 41

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

Question 42

Explain the rationale for nation-wide vitamin K prophylaxis in newborns.

Answer 42

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

Question 43

Discuss risk factors for developing vitamin K deficiency.

Answer 43

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

Question 44

Discuss possible nutrient-nutrient interactions for vitamin K.

Answer 44

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

Question 45

Answer 45

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)

Question 46

What do fat soluble compounds require for effective digestion & absorption?

Answer 46

Emulsification with bile salts

Question 47

What factors can affect absorption of vitamin K?

Answer 47

Absorption can be enhanced by dietary fats.

Absorption can be impaired by fat malabsorption disorders.

Question 48

What is a chylomicron?

Answer 48

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

Question 49

Answer 49

Answer → C

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

Question 50

Answer 50

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.

Question 51

Answer 51

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.

Question 52

Discuss the role of vitamin K in bone health.

Answer 52

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)

Question 53

Answer 53

Answer → A

Question 54

Discuss additional functions & emerging research involving vitamin K.

Answer 54

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)

Question 55

What are health implications associated with maintaining adequate vitamin K levels?

Answer 55

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

Question 56

Discuss the health implications of vitamin K deficiency.

Answer 56

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

Question 57

Answer 57

Answer → D

Question 58

Answer 58

Answer → D

Question 59

List the general functions of iron. [5]

Answer 59

Binding and transport of oxygen

Energy metabolism

Cofactor for various enzymes

Antioxidant protection

Antimicrobial function

Question 60

List some food sources for iron and state the chemical form in which iron occurs in these foods.

Answer 60

• 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

Question 61

Explain the processes and sites of heme iron digestion and absorption.

Answer 61

• 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

Question 62

Explain the processes and sites of non-heme iron digestion and absorption.

Answer 62

• 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.

Question 63

Explain the processes and sites of iron transport.

Answer 63

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

Question 64

Explain the processes and sites of iron storage.

Answer 64

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)

Question 65

Explain the processes and sites of iron metabolism and excretion.

Answer 65

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

Question 66

Explain how the chemical form of iron in food sources impacts iron bioavailability.

Answer 66

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.

Question 67

Discuss inhibitors [4] and enhancers [4] of non-heme iron digestion and absorption.

Answer 67

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

Question 68

Explain how whole body iron levels are regulated.

Answer 68

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

Question 69

Explain the stages in iron deficiency.

Answer 69

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

Question 70

Explain the stages of iron deficiency and discuss physiological and functional changes.

Answer 70

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

Question 71

Discuss the risk factors for developing iron deficiency.

Answer 71

Lower intake/absorption → vegetarians, vegans, gastrointestinal disease (e.g., ulcerative colitis)

Higher losses/demands → menstruating, blood loss, hookworm, infants and children, pregnant people

Question 72

Describe appropriate biomarkers for measurement of iron status.

Answer 72

• 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

Question 73

What oxidation states does iron exist in?

Answer 73

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.

Question 74

Answer 74

Answer → A

Heme iron is absorbed better than non-heme iron.

Question 75

Answer 75

Heme iron 25% absorbed

Mixed diet 18% absorbed

Vegetarian diet 10% absorbed

Question 76

Answer 76

Answer → D

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

Question 77

Compare iron RDA between males and females.

Answer 77

Notice that menstruation and pregnancy increase RDA considerably.

Question 78

How do vegetarians/vegans meet their iron requirements?

Answer 78

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

Question 79

What are the 3 possible fates of iron upon absorption into the enterocyte?

Answer 79

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.

Question 80

Answer 80

Answer → B

Question 81

Answer 81

Answer → B

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

Question 82

What does hepcidin do and how?

Answer 82

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

Question 83

What are hepcidin concentrations influenced by?

Answer 83

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.

Question 84

Describe regulation of cellular iron.

Answer 84

• 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

Question 85

Ferric forms of iron (Fe³⁺) absorb better than ferrous forms of iron (Fe²⁺).

True or False?

Answer 85

False.

Ferrous (Fe²⁺) forms better absorbed.

Question 86

Ferrous forms of iron (Fe²⁺) absorb better than ferric forms of iron (Fe³⁺).

True or False?

Answer 86

True.

Ferrous (Fe²⁺) forms better absorbed.

Question 87

Hepcidin is released at low transferrin saturation levels.

True or false?

Answer 87

False.

Hepcidin is released at high transferrin saturation levels

Question 88

Hepcidin is released at high transferrin saturation levels

True or False?

Answer 88

True.

Question 89

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

True or False?

Answer 89

True

Question 90

Hepcidin binds to ferroportin enhancing iron release from the enterocyte and macrophages.

True or False?

Answer 90

False.

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

Question 91

Hepcidin concentration are inversely correlated with iron demands.

True or False?

Answer 91

True.

Question 92

Hepcidin concentration are directly correlated with iron demands.

True or False?

Answer 92

False.

Hepcidin concentration are inversely correlated with iron demands.

Question 93

Hepcidin’s sole role is in the intestine.

True or False?

Answer 93

False.

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

Question 94

Depletion of iron stores (i.e., the first stage of iron deficiency), is most likely to affect […].

Answer 94

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

Question 95

Define anemia.

Answer 95

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

Question 96

Define iron deficiency anemia.

Answer 96

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

Question 97

Define iron deficiency anemia.

Answer 97

Mycrocytic hypochromic anemia

Question 98

Describe the distribution of iron deficiency.

Answer 98

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.

Question 99

Why is iron deficiency anemia more prevalent in pregnant people?

Answer 99

Pregnancy is associated with increased demands for iron.

Question 100

There is a high rate of iron deficiency in First Nation populations in Canada.

True or False?

Answer 100

True.

Question 101

What does iron deficiency adversely affect? [4]

Answer 101

• 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

Question 102

What are the adverse affects of iron deficiency anemia during pregnancy? [2]

Answer 102

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

Question 103

List 3 symptoms of iron deficiency.

Answer 103

Concave nails

PICA - the craving for non-food substances

Restless legs

Question 104

Zinc reduces iron bioavailability and iron absorption.

True or false?

Answer 104

True.

Question 105

Magnesium reduces iron bioavailability and iron absorption.

True or false?

Answer 105

True.

Question 106

Oxalic acid reduces iron bioavailability and iron absorption.

True or false?

Answer 106

True.

Question 107

Ascorbic acid reduces iron bioavailability and iron absorption.

True or false?

Answer 107

False.

Ascorbic acid enhances iron absorption.

Question 108

Phytic acid reduces iron bioavailability and iron absorption.

True or false?

Answer 108

True

Question 109

What are the causes of iron deficiency?

Answer 109

• 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

Question 110

What are the at risk population groups for iron deficiency?

Answer 110

Pregnant people

Vegetarians and vegans

Those with GI disease (e.g., ulcerative colitis)

Question 111

Describe a food-based approach as a treatment for iron deficiency including benefits and limitations.

Answer 111

• 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

Question 112

Discuss the benefits and limitations of iron supplementation as a treatment for iron deficiency.

Answer 112

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

Question 113

Discuss the daily dosage and potential side effects of iron supplementation as a treatment for iron deficiency.

Answer 113

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

Question 114

Discuss the various forms of iron supplements as a treatment for iron deficiency.

Answer 114

• 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.

Question 115

Discuss hemoglobin as a functional biomarker.

What are constraints?

Answer 115

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.

Question 116

Describe an indicator of iron supply.

Answer 116

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

Question 117

Describe an indicator of iron stores.

Answer 117

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

Question 118

What are the symptoms to iron overload?

Answer 118

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)

Question 119

What are potential causes of iron overload? [3]

Answer 119

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

Question 120

What is hereditary hemochromatosis?

Answer 120

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

Question 121

Iron absorption is tightly controlled and therefore, it is not possible to get ‘too much’ iron.

True or False?

Answer 121

False.

Question 122

Describe the hepcidin model of hereditary hemochromatosis.

Answer 122

Hepcidin controls iron release and iron absorption.

HFE-mutant → low hepcidin levels → uncontrolled iron absorption

Question 123

What are the symptoms of hereditary hemochromatosis?

Answer 123

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

Question 124

When do clinical signs of hereditary hemochromatosis appear?

Answer 124

at age > 40 years

Men outnumber women 3:1

Question 125

What are treatments of hereditary hemochromatosis?

Answer 125

Phlebotomy

Chelation therapy

Vegetarian diet

Question 126

Discuss acute iron poisoning. [2]

Answer 126

• 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

Question 127

In someone with undiagnosed hereditary hemochromatosis, transferrin saturation would be […].

Answer 127

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

Question 128

What stage of iron deficiency is Kate in?

Answer 128

Iron deficiency anemia (stage 3)

Question 129

Describe three factors that likely led to her deficiency.

Answer 129

GI disease decreases absorption

Polyphenols and oxalic acid in coffee decrease absorption

Menstruation (iron loss in blood)

Question 130

If Kate was already taking tums (calcium carbonate) for heartburn and now wanted to take iron to prevent anemia, how should she take these?

Answer 130

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

Question 131

What stage of iron deficiency is Kate in?

Answer 131

Iron deficiency anemia

Question 132

Answer 132

Answer → C

Question 133

Describe the functions of folate (vitamin B9).

Answer 133

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

Question 134

Discuss nutrient-nutrient interactions related to folate?

Answer 134

Folate functions interact with:

• Vitamin B12
• Vitamin B6
• Riboflavin (FMN/FAD)
• Choline

Question 135

Discuss nutrient-gene interactions related to folate.

Answer 135

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

Question 136

Discuss the diversity of folate coenzyme forms that are physiologically relevant.

Answer 136

Folate coenzyme forms:

• biologically active forms
• interchangeable
• substitutions at positions 5 & 10
• all reduced forms

Question 137

List examples of food sources (including supplements) for folate.

Answer 137

• 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 = pteroylpolyglutamates (>75%) in reduced forms (leafy greens, citrus, legumes)
• Most common form in fortified foods = folic acid (monoglutamate) → fortification of wheat flour is mandatory by law in Canada → grain and bakery products

Question 138

Explain the processes involved in folate digestion.

Answer 138

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

Question 139

Explain how the chemical forms of folate in food versus supplements (i.e., mono- and polyglutamates) influence the bioavailability of folate.

Answer 139

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

Question 140

Explain why the dietary recommendations are expressed in units of dietary folate equivalents.

Answer 140

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.

Question 141

Describe how folate status is assessed.

Answer 141

• 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

Question 142

Discuss risk factors for developing folate deficiency. [3 + 1?]

Answer 142

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?

Question 143

Explain the potential implications of high-dose folic acid intake, and what the UL is based on.

Answer 143

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.

Question 144

Explain the derivation and current recommendation for periconceptional folic acid supplementation.

Answer 144

• 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.

Question 145

Discuss potential implications of inadequate or excess folate intake for development of chronic disease.

Answer 145

• 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.

Question 146

What are methyl nutrients?

Answer 146

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

Question 147

How does DNA methylation influence how genes are expressed (& therefore cellular function)?

Answer 147

DNA methylation is an epigenetic modification to change expression of the DNA without changing the DNA sequence.

Methylation prevents DNA from being expressed.

Question 148

What is the biochemical role of folate (vitamin B9)? [3]

Answer 148

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

Question 149

Answer 149

Answer → A

Folate would be trapped as 5-methyl THF

Question 150

Answer 150

Answer → B

Folic acid is a synthetic form found in supplements

Question 151

Discuss ‘folic acid’. [3]

Answer 151

Folic acid

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

Question 152

Describe the chemical structure of folate (vitamin B9).

Answer 152

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

Question 153

Explain the what form, what site, and how folate is absorbed.

Answer 153

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

Question 154

Explain the processes involved in folate transport.

Answer 154

• 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)

Question 155

Explain the processes involved in folate excretion.

Answer 155

Excreted in urine → intact folate and products of folate catabolism

Some also secreted into bile → readsorption via enterohepatic circulation → minimal fecal excretion

Question 156

What decreases the activity of folate hydrolase? [3]

Answer 156

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

Question 157

What happens after folate is absorbed in enterocytes (and other cells)?

Answer 157

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

Question 158

Describe folate absorption across the basolateral membrane.

Answer 158

• 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.

Question 159

Answer 159

Answer → C

Question 160

Describe the transport, metabolism and storage of folate.

Answer 160

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

Question 161

Answer 161

Answer → C

Question 162

Explain the physiological implications of folate deficiency.

Answer 162

Macrocytic megaloblastic anemia

Question 163

Describe folate status in Canadians.

Answer 163

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

Question 164

What are the health implications of folate/B12 deficiency?

Answer 164

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

Question 165

What are the clinical signs of folate deficiency and symptoms related to anemia?

Answer 165

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

Question 166

Answer 166

Answer → B

Question 167

Discuss birth defects associated with low folate status.

Answer 167

Neural tube defects (NTDs)

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

Question 168

Answer 168

Answer → B

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

Question 169

What leads to high folate status?

Answer 169

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

Question 170

Discuss birth outcomes and childhood diseases associated with prenatal folic acid intake.

Answer 170

Question 171

Answer 171

Answer → D

Question 172

Name 2 research questions still remaining concerning folate/folic acid.

Answer 172

• 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?

Question 173

Adequate folate is important for reducing risk of… [3]

Answer 173

Prevention of anemia

Reducing risk of birth defects

Reducing risk of chronic disease (CVD, cancer, dementia)

Question 174

List the chemical forms of vitamin B12 that are physiologically relevant.

Answer 174

• 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

Question 175

Describe the metabolic functions of vitamin B12. [2]

Answer 175

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

Question 176

Discuss the nutrient-nutrient interaction between folate and vitamin B12 in the context of the ‘methyl-folate trap’.

Answer 176

• 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.

Question 177

List examples of dietary sources for vitamin B12 and mention the chemical forms of vitamin B12 present in food and supplements.

Answer 177

• 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

Question 178

Explain the processes involved in vitamin B12 digestion and absorption.

Answer 178

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%)

Question 179

Explain the processes involved in vitamin B12 transport.

Answer 179

• 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

Question 180

Explain the processes involved in vitamin B12 storage.

Answer 180

• 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).

Question 181

Explain the processes involved in vitamin B12 metabolism.

Answer 181

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.

Question 182

Explain the processes involved in vitamin B12 excretion.

Answer 182

• 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

Question 183

Explain the importance of R proteins, intrinsic factor and enterohepatic circulation regarding vitamin B12.

Answer 183

• 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.

Question 184

Discuss nutrient-gene interactions related to B12.

Answer 184

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

Question 185

Discuss risk factors for developing vitamin B12 deficiency.

Answer 185

• 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).

Question 186

Explain the physiological implications of vitamin B12 deficiency.

Answer 186

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

Question 187

Explain recommendations for older adults to prevent vitamin B12 deficiency.

Answer 187

• 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.

Question 188

Describe the biomarkers and methods used to assess vitamin B12 status. [3]

Answer 188

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.

Question 189

Answer 189

Answer → B

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

Question 190

Describe the function of vitamin B12 to remethylate homocysteine into methionine (cytosol).

Answer 190

• 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

Question 191

Answer 191

Answer → D

Question 192

Describe the role of vitamin B12 to convert methylmalonyl-CoA to succinyl-CoA (mitochondria).

Answer 192

• 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.

Question 193

Answer 193

Answer → C

Question 194

Answer 194

Answer → A

Question 195

Discuss DRI for vitamin B12.

Answer 195

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.

Question 196

Answer 196

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

Question 197

Answer 197

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).

Question 198

Explain the physiological implications of vitamin B12 sub-optimal status in relation to pregnancy outcomes [4] and neurological outcomes [3].

Answer 198

• 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.

Question 199

Discuss the implications of excess vitamin B12 intake.

Answer 199

No tolerable upper intake level for vitamin B12.

No toxicity or benefit reported from high doses of vitamin B12.

Question 200

Michelle is 65 years old. She consumes a generally healthy diet but has noticed her appetite decrease recently. She takes a folic acid with her daily IBD medication and calcium for bone health, but does not take any other nutrient supplements.

Answer 200

Answer → D

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

Question 201

Michelle is 65 years old. She consumes a generally healthy diet but has noticed her appetite decrease recently. She takes a folic acid with her daily IBD medication and calcium for bone health, but does not take any other nutrient supplements.

Answer 201

Answer → B

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

Question 202

Michelle is 65 years old. She consumes a generally healthy diet but has noticed her appetite decrease recently. She takes a folic acid with her daily IBD medication and calcium for bone health, but does not take any other nutrient supplements.

Answer 202

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.

Question 203

Michelle is 65 years old. She consumes a generally healthy diet but has noticed her appetite decrease recently. She takes a folic acid with her daily IBD medication and calcium for bone health, but does not take any other nutrient supplements.

Answer 203

Answer → D

Question 204

List physiologically relevant forms of choline. [5]

List four foods containing choline.

Answer 204

• 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

Question 205

List examples of natural food sources for choline.

Answer 205

Soybeans

Question 206

Explain the processes of choline digestion.

Answer 206

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

Question 207

Explain the processes of choline absorption.

Answer 207

• 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.

Question 208

Explain the processes of choline transport.

Answer 208

• 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

Question 209

Explain the processes of choline metabolism.

Answer 209

Choline is oxidized to betaine in liver and kidney.

Question 210

Explain the processes of choline excretion.

Answer 210

Excreted in urine, mainly as betaine.

Betaine = osomoregulator; i.e., maintains osmotic pressure in kidneys.

Question 211

Describe the functions of choline.

Answer 211

• 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.

Question 212

Discuss the interdependence of choline functions and synthesis with methyl donors.

Answer 212

Three SAM groups are necessary for the de novo synthesis of choline.

But we don’t make enough.

Question 213

Describe how choline was determined to be essential in the diet.

Answer 213

• 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.

Question 214

List a potential biomarker for measurement of choline status.

Answer 214

• 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.

Question 215

Discuss nutrient-nutrient interactions related to choline.

Answer 215

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

Question 216

Discuss nutrient-gene interactions related to choline.

Answer 216

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.

Question 217

Explain the physiological implications of choline deficiency.

Answer 217

• 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)

Question 218

Explain the potential implications of excess choline intake.

Answer 218

• 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

Question 219

Answer 219

Answer → C

Question 220

Answer 220

Answer → E

Component of acetylcholine.

Component of phosphatidylcholine & sphingomyelin.

Methylation

Component of PAF

All of the above basically.

Question 221

Describe choline in brain function.

Answer 221

• 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

Question 222

Describe dietary requirements for choline.

Answer 222

• 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.

Question 223

Answer 223

Answer → C

Question 224

Discuss choline during pregnancy.

Answer 224

• 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).

Question 225

Answer 225

Answer → B

This might change soon.

Question 226

Describe groups at risk of choline deficiency. [5]

Answer 226

• 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.

Question 227

Answer 227

Answer → D

Question 228

Answer 228

Answer → D

Question 229

List the chemical forms of thiamin that are physiologically relevant.

Answer 229

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

Question 230

Describe the metabolic functions of thiamin. [5]

Answer 230

(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

Question 231

List examples of natural food sources for thiamin and describe its form from each source.

Answer 231

• 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)

Question 232

Describe factors influencing thiamin stability. [3]

Answer 232

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

Question 233

Explain the related processes involved in thiamin digestion.

Answer 233

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

Question 234

Explain the related processes involved in thiamin absorption.

Answer 234

• 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

Question 235

Explain the related processes involved in thiamin transport.

Answer 235

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

Question 236

Where is thiamin stored in the body? How long does it take for depletion of body stores?

Answer 236

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.

Question 237

Explain the related processes involved in thiamin excretion.

Answer 237

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

Question 238

Discuss risk factors for developing thiamin deficiency.

Answer 238

• 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)

Question 239

Explain the physiological implications of thiamin deficiency.

Answer 239

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

Question 240

Describe how to assess thiamin status. [3]

Answer 240

• (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

Question 241

Answer 241

Answer → D

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

Question 242

Answer 242

Answer → D

Question 243

Answer 243

Answer → D

Question 244

Answer 244

Answer → C

Question 245

Describe dry beriberi.

Answer 245

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)

Question 246

Describe wet beriberi.

Answer 246

Edematous beriberi

Characteristics:

• More extensive cardiovascular system damage → cardiomegaly (enlarged heart); tachycardia (rapid heartbeat); heart failure
• Peripheral edema

Question 247

Describe acute beriberi.

Answer 247

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

Question 248

Describe Wernicke Encephalopathy.

Answer 248

• 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

Question 249

What is a coenzyme?

Answer 249

Non-protein, organic molecule that helps an enzyme function.

Vitamins with coenzyme function → B vitamins!

Question 250

Thiamin has a UL.

True or False?

Answer 250

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

Question 251

Thiamin does not have a UL.

True or False?

Answer 251

True.

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

Question 252

List the chemical forms of B6 that are physiologically relevant.

Answer 252

Active coenzyme form = pyridoxal phosphate (PLP)

6 different vitamers → alcohol form, aldehyde form, and amine form → which can all be phosphorylated and/or interconverted

Question 253

List examples of natural food sources for vitamin B6.

Answer 253

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.

Question 254

Explain the processes involved in vitamin B6 digestion.

Answer 254

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

Question 255

Explain the processes involved in vitamin B6 absorption.

Answer 255

• 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

Question 256

Explain the processes involved in vitamin B6 transport.

Answer 256

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

Question 257

Explain the processes involved in vitamin B6 storage.

Answer 257

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

Question 258

Explain the processes involved in vitamin B6 metabolism.

Answer 258

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

Question 259

Explain the processes involved in vitamin B6 excretion.

Answer 259

• 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

Question 260

Briefly list the functions of vitamin B6. [5]

Answer 260

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)

Question 261

Discuss possible nutrient-gene interactions related to vitamin B6. [3]

Answer 261

• 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

Question 262

Discuss nutrient-nutrient interactions related to vitamin B6. [6]

Answer 262

• 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.

Question 263

Briefly list how vitamin B6 status is assessed.

Answer 263

• 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

Question 264

Discuss the prevalence and risk factors for developing a vitamin B6 deficiency [2].

Answer 264

• 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

Question 265

What are the physiological implications of vitamin B6 deficiency. [6]

Answer 265

• 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

Question 266

Explain the physiological implications of excess vitamin B6 intake.

Answer 266

• 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

Question 267

Answer 267

Answer → D

We only need ~1mg, not 100mg!

Question 268

Answer 268

Answer → D

Pyridoxal phosphate (PLP)

Question 269

Answer 269

Answer → C

Pyridoxine (PN) → supplement form

Question 270

Answer 270

Answer → C

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

Question 271

Answer 271

Answer → D

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

Question 272

Answer 272

Answer → D

Question 273

Answer 273

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.

Question 274

Describe the role of vitamin B6 in transamination.

Answer 274

PLP = coenzyme in transamination reactions

Alanine aminotransferase (ALT)

Aspartate aminotransferase (AST)

Question 275

Describe the role of vitamin B6 in decarboxylation reactions. [2]

Answer 275

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

Question 276

Describe the role of vitamin B6 in cleavage reactions.

Answer 276

PLP = coenzyme in (side-chain) cleavage reactions

Shown: serine → glycine (important in interconversion of non-essential a.a.)

Question 277

Describe the role of vitamin B6 in transsulfuration.

Answer 277

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.

Question 278

What is the most commonly used indicator for vitamin B6?

Answer 278

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)

Question 279

Give an example of a direct method of vitamin B6 assessment.

Answer 279

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

Question 280

Give an example of an indirect method to assess vitamin B6 status.

Answer 280

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

Question 281

What is a long-term status biomarker for vitamin B6?

Answer 281

Transaminase activity - indirect method

• Erythrocyte aspartic acid transferase and erythrocyte alanine transferase
• The higher the activation coefficient, the lower the vitamin B6 status.

Question 282

What does suboptimal vitamin B6 status increase risk of? [3]

Answer 282

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

Question 283

What are high-dose vitamin B6 supplements used for? [4]

Answer 283

Carpal tunnel

Premenstrual syndrome (PMS)

Morning sickness (nausea & vomiting of pregnancy)

Depression

Question 284

What is riboflavin?

Answer 284

• 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)

Question 285

List food items that are good sources of riboflavin (B2).

Answer 285

• 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

Question 286

Explain the processes involved in riboflavin digestion.

Answer 286

• 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

Question 287

Explain the processes involved in riboflavin absorption.

Answer 287

• 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

Question 288

Explain the processes involved in riboflavin transport.

Answer 288

• 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.

Question 289

Where is riboflavin mainly stored in the body? How long are body stores estimated to last?

Answer 289

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

Question 290

Explain the processes involved in riboflavin metabolism.

Answer 290

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

Question 291

Explain the processes involved in riboflavin excretion.

Answer 291

• 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

Question 292

Describe the signs of riboflavin deficiency.

Answer 292

• 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

Question 293

Describe risk factors for riboflavin deficiency or suboptimal status. [4]

Answer 293

• (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

Question 294

Describe methods for assessing riboflavin status. [4]

Answer 294

• 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

Question 295

Describe the metabolic function of riboflavin. [10]

Answer 295

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

Question 296

Describe examples of energy metabolism pathways in which riboflavin has a role. [3]

Answer 296

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

Question 297

Explain possible nutrient-nutrient interactions for riboflavin. [4]

Answer 297

• 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.

Question 298

Explain possible nutrient-gene interactions for riboflavin.

Answer 298

• 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.

Question 299

Answer 299

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).

Question 300

Answer 300

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

Question 301

Answer 301

Answer → E

Question 302

List the different chemical forms of riboflavin.

Answer 302

• 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.

Question 303

Describe suboptimal riboflavin status.

Answer 303

• 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

Question 304

What is used to estimate riboflavin requirement in adults?

Answer 304

• 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)

Question 305

Plasma riboflavin/FAD/FMN reflects dietary intake when the tissues are saturated.

True or False?

Answer 305

False.

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

Question 306

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

True or False?

Answer 306

True

Question 307

Urinary excretion of riboflavin reflects dietary intake when tissues are saturated.

True or False?

Answer 307

True.

Question 308

Urinary excretion of riboflavin reflects recent dietary intake of riboflavin.

True or False?

Answer 308

False.

It reflects dietary intake when tissues are saturated.

Question 309

Describe the gold standard for measuring riboflavin status.

Answer 309

Erythrocyte glutathione reductase activation coefficient

• Measures the FAD dependent enzyme erythrocyte glutathione reductase

Question 310

Describe the cutoff values for deficient/suboptimal/optimal riboflavin (vitamin B2) status, and the potential for new biomarkers.

Answer 310

• 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

Question 311

Describe riboflavin’s role in antioxidant metabolism.

Answer 311

Reduction of oxidized form of glutathione

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

Question 312

Describe the interaction between FMN & Vitamin B6.

Answer 312

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

Question 313

Describe the interaction between riboflavin and niacin.

Answer 313

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

Question 314

Answer 314

Answer → B

Question 315

Discuss the health implications of nutrient-gene interactions associated with riboflavin.

Answer 315

• 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).

Question 316

Discuss lifestyle factors for blood pressure reduction.

Answer 316

• 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

Question 317

There is a UL for riboflavin.

True or False?

Answer 317

False.

No UL for riboflavin!

Only reported side effect of high intake levels → bright yellow urine

Question 318

There is no UL for riboflavin.

True or False?

Answer 318

True.

No UL for riboflavin!

Only reported side effect of high intake levels → bright yellow urine

Question 319

In a Vancouver study, although most women met the EAR for riboflavin intake, many had deficient/suboptimal biochemical status.

The implications of suboptimal/deficient biochemical status are unknown.

What does this suggest further research is needed for? [2]

Answer 319

More research is needed to:

• Develop biomarkers to assess the prevalence of riboflavin deficiency/suboptimal status across populations.
• Determine health implications of suboptimal status.

Question 320

Answer 320

Answer → C

Personalized nutrition approach

Question 321

Describe the main metabolic function of biotin in the body. [4]

Answer 321

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

Question 322

List food items that are good sources of biotin.

Answer 322

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.

Question 323

Describe the relevance of biocytin and biotinidase.

Answer 323

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

Question 324

Describe the signs and symptoms of biotin deficiency. [3]

Answer 324

• 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

Question 325

List the chemical forms of niacin that are physiologically relevant.

Answer 325

NAD⁺ → nicotinamide adenine dinucleotide

NADP⁺ → nicotinamide adenine dinucleotide phosphate

Question 326

Explain why the dietary requirements for niacin are expressed in units of niacin equivalents (NE) and how that translates into dietary advice.

Answer 326

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)

Question 327

Describe the metabolic functions of niacin.

Answer 327

Coenzyme role

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

Question 328

Describe the pharmacological uses of niacin. [2]

Answer 328

• 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.

Question 329

Explain the physiological implications of niacin deficiency.

Answer 329

• 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

Question 330

What is pantothenic acid a component of? [2]

Answer 330

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

Question 331

List the forms of pantothenic acid in food and comment on the distribution of pantothenic acid in foods.

Answer 331

• 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

Question 332

Discuss the likelihood of developing pantothenic acid deficiency.

Answer 332

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

Question 333

Discuss the physiological implications of pantothenic acid deficiency.

Answer 333

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

Question 334

Answer 334

Answer → A

Biotin is bound to avidin in egg whites.

Question 335

What is the prevalence and what are the risk factors/causes for biotin deficiency [5]?

Answer 335

• 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

Question 336

Answer 336

Answer → C

Biotin deficiency is rare.

Question 337

Discuss biotin for hair & nails.

Answer 337

• 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

Question 338

What are the DRI for biotin?

Answer 338

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

Question 339

Biotin has a UL.

True or False?

Answer 339

False.

No UL for biotin.

Question 340

Biotin does not have a UL.

True or False?

Answer 340

True.

Question 341

Describe the chemical structure of niacin in food sources.

Answer 341

• 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

Question 342

Describe the endogenous synthesis of niacin. What does the pathway depend on?

Answer 342

Precursor = tryptophan

Pathway depends on:

• Riboflavin (as FAD)
• Vitamin B6 (as PLP)
• Iron

Question 343

Answer 343

Answer → D

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

Question 344

Answer 344

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)

Question 345

Describe the coenzyme role of NAD⁺. [5]

Answer 345

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

Question 346

Describe the coenzyme roles of NADPH. [5]

Answer 346

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

Question 347

Which form of niacin is involved in folate coenzyme synthesis?

Answer 347

NADPH

Question 348

Jerome consumes a smoothie with each meal and wants to know whether it is ok to add 6 raw egg whites for extra protein. If he does this, what nutrient deficiency would he be at risk of, and what symptoms would he experience as a result?

Answer 348

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

Question 349

Sally has just done a DNA analysis and discovers that she has a SNP in the gene encoding biotinidase and holocarboxylase synthase. How do these influence her nutrient requirements?

Answer 349

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.

Question 350

Calley wants to know if she should take vitamin supplements for hair and nail growth. Do these actually work?

Answer 350

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.

Question 351

Why are the DRI for niacin expressed as NE?

Answer 351

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

Question 352

Why was niacin deficiency historically common in the Americas?

Answer 352

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.

Question 353

For what conditions are high dose niacin supplements prescribed [2]? Are there any side effects associated with this [4]?

Answer 353

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)*

Question 354

Diana is feeling low in energy and thinks she may be low in pantothenic acid. What is the role of pantothenic acid in energy metabolism? How likely is a pantothenic acid deficiency?

Answer 354

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)

Question 355

Which form of niacin is involved in the hexose monophosphate shunt?

Answer 355

NADPH → formation for biosynthetic processes

Question 356

What is Pellagra?

Answer 356

Niacin deficiency disease

• Dermatitis
• Dementia
• Diarrhea
• Death

There is little storage of niacin → early features of pellagra can occur after 45 days of depletion

Question 357

What are the health implications of niacin excess intake? [4]

Answer 357

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

Question 358

There is no UL for niacin.

True or False?

Answer 358

False.

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

Question 359

There is a UL for niacin.

True or False?

Answer 359

True.

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

Question 360

Answer 360

Answer → C

For each 60g of tryptophan = 1 NE

Question 361

Last slide → You consumed three chicken sandwiches today providing 22 mg niacin and 1000 mg tryptophan.

Answer 361

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.

Question 362

What are the biochemical roles of coenzyme-A? [3] Which essential nutrient is a component of CoA?

Answer 362

• 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

Question 363

Answer 363

Answer → A

Question 364

What is the role of acyl carrier protein? Which essential nutrient is a component of acyl carrier protein?

Answer 364

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.

Question 365

Discuss the DRI for pantothenic acid.

Answer 365

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

Question 366

Pantothenic acid has an AI.

True or False?

Answer 366

True.

Question 367

Pantothenic acid has an RDA.

True or False?

Answer 367

False.

Pantothenic acid has AI values for all population groups.

Question 368

Answer 368

Answer → C

Question 369

Which vitamins are grain & bakery products fortified with in Canada? [5]

Answer 369

Folic acid

Riboflavin

Iron

Niacin

Thiamin

‘FRINT’

Question 370

Individuals at risk for developing thiamin deficiency include:

A. older adults

B. people with certain diseases, including IBD

C. Alcoholics

D. All of the above

E. None of the above

Answer 370

Answer → D

Question 371

The metabolic functions of riboflavin include:

A. Conversion of pyridoxal 5’-phosphate and pyridoxamine phosphate to pyridoxine phosphate

B. In the folate cycle, in formation of 5-methyl THF

C. As an electron donor in fatty acid oxidation and the TCA cycle

D. Formation of choline

E. All of the above

Answer 371

Answer → B

Question 372

The functions of folate include:

A. Coenzyme for MTHFR, which transfers a methyl group to a methyl acceptor, such as protein or DNA

B. Formation of the amino acids serine and glycine

C. Synthesis of homocysteine

D. Two of the above

E. All of the above

Answer 372

Answer → B

Question 373

Intrinsic factor is required for the absorption of which vitamin?

Answer 373

Vitamin B12

Question 374

Which of the following vitamins has a Tolerable Upper Intake Level established?

A. thiamin

B. riboflavin

C. vitamin B6

D. vitamin B12

Answer 374

Answer → C

Question 375

Vitamin K deficiency in adults is most likely due to:

A. Oxalic acid in food

B. Achlorhydria

C. Chronic antibiotic therapy

D. A high-fibre diet.

Answer 375

Answer → C

Question 376

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

Answer 376

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⁺].

Question 377

Consuming large amounts of raw egg whites could lead to:

A. Ariboflavinosis

B. Beriberi

C. Hair loss

D. Elevated homocysteine

Answer 377

Answer → C

Question 378

An increase in blood pyruvate and lactic acid could be explained by a deficiency of:

A. Riboflavin

B. Thiamin

C. Vitamin B6

D. Folate

Answer 378

Answer → B

Question 379

The primary biochemical function of vitamin K in the body is:

A. Synthesis of blood clotting proteins

B. Synthesis of bone forming enzymes

C. Gamma-carboxylation of glutamic acid residues

D. Synthesis of glutamic acid rich peptides

Answer 379

Answer → C

Question 380

Wet beriberi can be distinguished from dry beriberi because:

A. Wet beriberi is more common in alcoholics

B. Wet beriberi is more common in the elderly

C. Wet beriberi is associated with peripheral edema

D. Wet beriberi impairs glucose metabolism

Answer 380

Answer → C

Question 381

The active form of vitamin K in the body is:

A. The fully oxidized quinone form

B. The reduced form

C. The oxidized epoxide form

D. The phylloquinone form

Answer 381

Answer → B

Question 382

Functions of iron in the body include all of the following EXCEPT:

A. Antioxidant roles

B. Oxygen transport

C. Cofactor for enzymes

D. Synthesis of s-adenosylmethionine (SAM)

Answer 382

Answer → D

Question 383

Compared to people who consume animal products, those following a vegetarian diet need:

A. More iron, as iron is less bioavailable from plant sources

B. Less iron, as iron is more bioavailable from plant sources

C. The same amount of iron, as iron is abundant in both plant and animal sources

Answer 383

Answer → A

Question 384

The UL for folic acid is based on masking symptoms of B12 deficiency. The metabolic basis for that is:

A. High doses of folic acid can overcome the need for vitamin B12 for synthesis of methionine

B. High doses of folic acid can overcome the need for vitamin B12 for conversion of methylmalonyl-CoA to succinyl-CoA

C. High doses of folic acid ensure adequate folate for synthesis of nucleotides

D. High doses of folic acid overcome the trapping of folate in cells

Answer 384

Answer → C

Question 385

The form of folate that is best absorbed into the enterocyte is:

A. Folic acid in the monoglutamate form

B. Folic acid in the polyglutamate form

C. Reduced folates in the monoglutamate form

D. Reduced folates in the polyglutamate form

E. Folic acid and reduced folates in the monoglutamate form

F. Folic acid and reduced folates in the polyglutamate form

Answer 385

Answer → E

Question 386

Red blood cell folate is a better long term indicator of folate status because:

A. RBCs will show megaloblastic anemia with inadequate folate

B. RBCs will show microcytic anemia without adequate folate

C. RBCs are in equilibrium with tissue stores

D. RBC folate reflects recent intake

E. RBCs take up folate during formation

Answer 386

Answer → E

Question 387

Water-soluble vitamins are not stored, but readily excreted, with the one exception that we can store […] in the liver.

Answer 387

Vitamin B12

Question 388

Water soluble forms of choline include all of the following EXCEPT:

A. Glycerocholine

B. Phosphocholine

C. Free choline

D. Sphingomyelin

Answer 388

Answer → D

Question 389

Which of the following is the likely link between vitamin B6 and depression?

A. Vitamin B6 is needed for decarboxylation to form serotonin and dopamine

B. Vitamin B6 is needed for transamination reactions

C. Vitamin B6 is needed for synthesis of niacin

D. Vitamin B6 is needed for synthesis of acetylcholine

Answer 389

Answer → A

Question 390

A main source of riboflavin in Canadian diets is:

A. Dark green leafy vegetables

B. Dairy

C. Fruits

D. Starchy vegetables

Answer 390

Answer → B

Question 391

The only B vitamin (that we have discussed) that is absorbed solely by passive diffusion is:

A. Folate

B. Vitamin B12

C. Thiamin

D. Riboflavin

E. Vitamin B6

Answer 391

Answer → E

Question 392

When iron is consumed in excess of needs, the excess is:

A. Excreted in urine

B. Excreted in blood

C. Excreted in feces

D. Sloughed off with the intestinal cell turnover

Answer 392

Answer → D

Question 393

Most of our body iron is found in

A. Myoglobin in muscles

B. Hemoglobin in liver

C. Hemoglobin in RBCs

D. Stored as ferritin in the liver

E. Bound to enzymes in body tissues

Answer 393

Answer → C

Question 394

If someone had low ferritin but adequate transferrin saturation and hemoglobin, they would likely be in which stage of iron deficiency:

A. Iron adequate

B. Iron depletion

C. Iron deficiency erythropoiesis

D. Iron deficiency anemia

Answer 394

Answer → B

Question 395

Why is the recommendation for choline based on an AI?

Answer 395

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

Question 396

What are the manifestations of inadequate choline intake in humans?

Answer 396

Non-alcoholic fatty liver disease and liver damage

Question 397

What are the effects of excess choline intake? [5]

Answer 397

Fishy body odour

Vomiting

Sweating

Salivation

Hypotension

Question 398

List three examples of good food sources of choline (can be food groups or specific foods).

Answer 398

Eggs

Peanuts

Beef

Question 399

A sensitive method to assess nutritional status for some nutrients is to measure the activity of an enzyme that requires the vitamin as a cofactor. Explain how this works conceptually and then provide an example.

Answer 399

• 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.
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Question 400

Sally is a healthy 24 year old female. For breakfast, she had the following. She also took a supplement with 1000ug of folic acid. What was her DFE intake?

Does Sally need the supplement?

Her blood levels indicate high levels of folic acid. Explain why from a dietary perspective and a physiological perspective.

Answer 400

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.

Question 401

Which of the nutrients covered (so far) have an AI? [4]

Answer 401

Choline

Biotin

Pantothenic acid

Vitamin K

Question 402

Which of the nutrients covered (so far) have an RDA? [7]

Answer 402

Iron

Thiamin (B1)

Riboflavin (B2)

Niacin (B3)

B6

Folate (B9)

B12

Question 403

Which of the nutrients covered (so far) have a UL? [5]

Answer 403

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

Question 404

Which of the nutrients covered so far do not have a UL? [6]

Answer 404

Thiamin (B1)

Riboflavin (B2)

Pantothenic acid (B5)

Biotin (B7)

B12

Vitamin K