Final Exam Material

Question 1

What is oxidative stress?

Answer 1

• Reactive oxygen species and other reactive species oxidize (= ‘steal electrons’) from DNA, protein, lipids, etc.
• Oxidation = chemical reaction that produces free radicals, leading to chain reactions that may cause damage to cells and tissues.

Question 2

What is an antioxidant?

Answer 2

Protectors to oxidative stress

Antioxidant = molecule that inhibits the oxidation of other molecules

Question 3

List some reactive species.

Answer 3

• Highly reactive, oxygen containing molecules often free radicals with unpaired electrons e.g., superoxide radical, hydroxyl radical, and hydrogen peroxide.
• Reactive, nitrogen species e.g., nitric oxide
• Other reactive species e.g., thiyl RS, trichloromethyl

Question 4

How are reactive species generated? [2]

Answer 4

• Exposure to exogenous substances
  
  • Chemicals in environment (pollutants)
  • Smoking
  • Drugs
  • Radiation
• Physiological processes
  
  • Enzymatic reactions, oxidases
  • Electron transport chain
  • Immune defense (superoxide = antimicrobial)

Question 5

Discuss the consequences of PUFA oxidative damage. [3]

Answer 5

(Membrane) lipid peroxidation → (1) loss of membrane fluidity, (2) receptor functions, and potentially (3) cellular lysis

Question 6

Discuss the consequences of protein degradation by oxidative damage. [3]

Answer 6

(1) Cross-linking; (2) inactivation; (3) denaturation

Question 7

Discuss the consequences of carbohydrate oxidative damage. [2]

Answer 7

Altered glycoprotein function → (1) hormonal and neurotransmitter receptors, (2) cell recognition

Question 8

Discuss the consequences of nucleic acid oxidative damage. [3]

Answer 8

(1) DNA damage; (2) Mutations; (3) Carcinogenesis

Question 9

Discuss oxidative stress and disease.

Answer 9

Oxidative stress may play a role in multiple chronic diseases.

• Atherosclerosis → development of plaque in vessels
• Cancer
• Cataracts → clouding of lens due to protein oxidation
• Autoimmune diseases
• Lung damage

Question 10

Discuss oxidative stress and aging.

Answer 10

• Free-radical theory of aging = aging process due to cumulative oxidative damage to cells → minimizing ROS/free radicals may be ‘key’ to anti-aging

Question 11

Name antioxidant systems in the body [2] and give three examples in each category.

Answer 11

• Enzymes
  
  • Catalase (contains 4 heme groups)
  • Cu/Zn superoxide dismutase (SOD)
  • glutathione peroxidase (selenium)
• Micronutrients
  
  • Vitamin C
  • Vitamin E
  • Beta-carotene (pre-cursor to vitamin A)

Question 12

Answer 12

Answer → D

Catalase contains 4 heme groups

Question 13

List the main food sources and forms of zinc in the diet.

Answer 13

• Food sources → meat and seafood
  
  • Zinc content of foods often associated with protein content of foods.
  • Plant sources have less zinc and zinc is less well absorbed from plant sources.
• Forms in diet → Zn²⁺
  
  • Usually bound to protein or nucleic acid
  • Supplements = zinc salts (e.g., zinc sulfate, zinc gluconate)

Question 14

Explain the digestion of zinc.

Answer 14

• Most zinc bound to proteins & nucleic acids → first step in digestion is to release zinc form proteins & nucleic acids
• Zinc released from proteins and nucleic acids by HCl (denatures protein) and enzymes (proteases, nucleases) in the stomach and small intestine

Question 15

Explain the absorption of zinc.

Answer 15

• Carrier-mediated through ZIP-4 = major transporter of zinc across brush border
• ZIP-4 degraded with high Zn status = mechanism for maintaining Zn homeostasis
• Minor pathways;
  
  • DMT1
  • With amino acids via amino acid carriers
  • Paracellular diffusion at high intakes (>20 mg)
• No passive diffusion for uptake of zinc because free zinc has a charge → charged elements do not diffuse across phospholipid bilayer

Question 16

Explain the transport of zinc.

Answer 16

• In plasma → bound to proteins (e.g., albumin) or amino acids.
• Tissue uptake via transporter → ZIPs as importers (also DMT1); zinc transporters (ZnTs) as exporters
• Within cells → zinc bound to proteins

Question 17

Explain the storage of zinc.

Answer 17

• Bound to metallothionein → storage complex for zinc → metallothionein synthesis stimulated by zinc
• Total body zinc = 1.5-3 grams → mostly in (1) liver, (2) kidneys, (3) muscle, (4) skin and (5) bones
• Metallothionein is involved in short-term storage of zinc, and it has other functions

Question 18

Explain the excretion of zinc. [2]

Answer 18

• Fecal excretion (main) → increases with increasing zinc intake
  
  • Unabsorbed zinc
  • Digestive enzymes secreted from pancreas → some may be reabsorbed
  • Purposeful intestinal excretion of zinc
    
    • Transport of zinc from blood across basolateral membrane into enterocyte, through brush border membrane into lumen.

Question 19

Describe factors influencing zinc bioavailability.

Answer 19

• Less absorption with higher intakes
• Animal sources > plant sources
• Enhancers → a.a. organic acids, higher acidity
• Inhibitors → phytic acid, oxalic acid, polyphenols, non-heme iron (found in plant-based food sources, hence lower bioavailability of plant-based zinc)

Question 20

Discuss how whole body zinc homeostasis is maintained.

Answer 20

• Zinc homeostasis is maintained by decreased absorption and increased excretion at high intakes and status
  
  • Decrease absorption through decreased ZIP-4
  • Increased excretion through transport of zinc from blood into the lumen of the gut

Question 21

Describe the main functions of zinc. [6]

Answer 21

• Component of metalloenzymes (>300)
• Gene expression → zinc fingers → gene transcription
• Membrane stabilization
• Insulin response and glucose tolerance → signalling and release; impaired glucose tolerance in zinc deficiency
• Immune function → development and differentiation of immune cells
• Sexual maturation → fertility, reproduction and development

Question 22

Discuss nutrient-nutrient interactions for zinc. [4]

Answer 22

1. Iron → zinc and iron absorbed by DMT1 in intestine; high zinc intake can decrease iron absorption
2. Calcium → zinc supplements may interfere with calcium absorption (particularly at low calcium intake)
3. Copper → high zinc intake may ‘trap’ copper bound to metallothionein
4. Vitamin A → zinc needed for conversion of retinol to retinal → zinc needed in synthesis of retinol-binding protein that transports vitamin A in the blood

Question 23

Discuss the symptoms of zinc deficiency in children [3], adults [6], and symptoms shared by both children & adults [3].

Answer 23

• Children
  
  • Growth retardation (stunting)
  • Skeletal abnormalities
  • Delayed sexual maturation
• Adults
  
  • Anorexia
  • Lethargy
  • Blunting of sense of taste
  • Vision problems
  • Impaired immune function
  • Glucose intolerance
• Both
  
  • Diarrhea → exacerbates zinc deficiency through faecal losses in a positive feedback loop → must interrupt this cycle to address underlying cause
  • Poor wound healing
  • Skin rash/lesions/dermitisis

Question 24

Discuss the risk factors for developing a zinc deficiency. [4]

Answer 24

• (1) Inadequate intake → low/no intake of animal source food e.g., vegetarian diet, low socioeconomic status
• (2) Older adults → reduced gastric acidity, often poorer nutrition
• (3) Alcohol consumption → reduces intestinal zinc absorption and increases urinary zinc excretion
• (4) Diseases/conditions that cause malabsorption e.g., IBD, chronic diarrhea, sickle cell disease)

Question 25

Describe the symptoms of zinc toxicity, both acute (3) and chronic (2).

Answer 25

• Acute toxicity
  
  • Vomiting
  • Abdominal cramps
  • GI distress
• Chronic toxicity
  
  • Copper deficiency
  • Anemia → copper is needed for the transport of iron

Question 26

Discuss current evidence for use of zinc in prevention or treatment of common colds.

Answer 26

• Zinc is important for immune function.
• Overall, research suggests that high dose zinc supplements taken at the onset of a cold (i.e., the start of noticeable symptoms) may reduce onset and duration.

Question 27

What is zinc?

Answer 27

Zinc is an essential micromineral, or trace element

Mostly occurs in the body in the form of Zn²⁺

Question 28

Zinc content of foods often associated with protein content of foods.

True or False?

Answer 28

True.

Question 29

Zinc content of foods often associated with CHO content of foods.

True or False?

Answer 29

False.

• Zinc content of foods often associated with protein content of foods.

Question 30

Plant sources have less zinc and zinc is less well absorbed from plant sources.

True or False?

Answer 30

True.

Question 31

Plant sources have more zinc and zinc is better absorbed from plant sources.

True or False?

Answer 31

False.

• Plant sources have less zinc and zinc is less well absorbed from plant sources.

Question 32

Describe the DRI for zinc.

Answer 32

RDA → based on amount needed maintain balance as well as on estimates of zinc absorption and body losses

Tolerable Upper Intake Level = 40mg/day

Question 33

Answer 33

Answer → C

Question 34

What are three minor pathways for zinc absorption?

(i.e., not ZIP-4)

Answer 34

• Minor pathways;
  
  • DMT1
  • With amino acids via amino acid carriers
  • Paracellular diffusion at high intakes (>20 mg)

Question 35

What is a mechanism for maintaining zinc homeostasis?

Answer 35

ZIP-4 degraded with high Zn status

Question 36

What is the overall absorption rate of zinc? What influences this rate? [2]

Answer 36

• 20-50% of ingested zinc is absorbed
• Absorption rate is influenced by zinc intake and enhancers/inhibitors

Question 37

Describe how zinc intake affects its absorption rate.

Answer 37

• Less absorption with higher intakes
  
  • 100% absorbed at intake levels <1mg
  • 30-40% absorbed at intake level of about 12mg

Question 38

What are enhancers of zinc bioavailability? [2]

Answer 38

• Amino acids, organic acids → form soluble complexes with zinc
• Higher acidity

Question 39

What are inhibitors of zinc bioavailability? [4]

Answer 39

• (1) Phytic acid, (2) oxalic acid, (3) polyphenols → form complexes with zinc that are not absorbed
• (4) Non-heme iron (particularly at high doses)

Question 40

What are the 3 possible fates of zinc absorbed into an enterocyte?

Answer 40

• Used intracellularly for biochemical functions
• Stored, or sequestered in vesicles or Golgi network
• Transported through the cytosol bound to proteins, across the basolateral membrane (through ZnT1)

Question 41

Zinc is transported in free form in plasma.

True or False?

Answer 41

False.

Zinc is bound to proteins (e.g., albumin) or amino acids in plasma.

Question 42

How is zinc transported in the blood?

Answer 42

Bound to proteins (e.g., albumin) or amino acids

Question 43

How is zinc taken up into cells?

Answer 43

• ZIPs as importers; also DMT1
• Zinc transporters (ZnTs) as exporters

Question 44

How is zinc transported within cells?

Answer 44

• Zinc is bound to proteins in:
  
  • Nucleus (30-40%)
  • Cytosol (50%)
  • Cell membrane (10%)

Question 45

Metallothionein has a higher affinity for zinc than copper.

True or False?

Answer 45

False.

Metallothionein has a higher affinity for copper than zinc → copper bound to metallothionein in enterocyte become ‘trapped’ → higher zinc in the body stimulates synthesis of metallothionein in enterocyte → zinc-induced copper deficiency possible

Question 46

Metallothionein has a higher affinity for copper than zinc.

True or False?

Answer 46

True.

Copper bound to metallothionein in enterocyte become ‘trapped’ → higher zinc in the body stimulates synthesis of metallothionein in enterocyte → zinc-induced copper deficiency possible

Question 47

What are the functions of metallothionein? [5]

Answer 47

• Storage complex for zinc
• Intracellular transport of zinc
• Detoxifying heavy metals
• Stabilizing membranes
• Antioxidant

Question 48

A copper-induced zinc deficiency is possible.

True or False?

Answer 48

False.

• A zinc-induced copper-deficiency is possible because higher zinc in the body stimulates metallothionein synthesis in enterocyte → metallothionein has a higher affinity for copper than zinc

Question 49

A zinc-induced copper deficiency is possible.

True or False?

Answer 49

True.

A zinc-induced copper-deficiency is possible because higher zinc in the body stimulates metallothionein synthesis in enterocyte → metallothionein has a higher affinity for copper than zinc

Question 50

Answer 50

Answer → A

Amino acids and organic acids can form soluble complexes with zinc that enhance absorption.

Question 51

Answer 51

Answer → B

Zinc is not excreted through biliary excretion mechanisms.

Question 52

How does zinc function as a component of >300 metalloenzymes?

Answer 52

Zn²⁺ provides structural integrity to enzymes and participates in reaction at catalytic site.

Question 53

Give examples of zinc function through its cofactor role in metalloenzymes. [5]

Answer 53

• Antioxidant function through role in Cu/Zn superoxide dismutase (SOD)
• Synthesis and degradation of proteins, carbohydrates, lipids, DNA and RNA → zinc functions as cofactor for various enzymes including kinases, phosphorylases, polymerases
• Digestion of nutrients (e.g., folate hydrolase, alkaline phosphatase)
• Wound healing (matrix metalloproteinase)
• Taste (gustin)

Question 54

Describe the role of zinc in gene expression.

Answer 54

• Zinc fingers → structural role regulating gene transcription (e.g., estrogen receptor; glucocorticoid receptor

Question 55

Answer 55

Answer → D

Question 56

Answer 56

Answer → C

Question 57

Answer 57

Answer → D

Impaired copper absorption is an effect of zinc toxicity not deficiency.

Question 58

Zinc has a UL.

True or False?

Answer 58

True.

40 mg/day

Question 59

Zinc does not have a UL.

True or False?

Answer 59

False.

Zinc UL = 40mg/day

Question 60

Describe the physiological implications of Menke’s disease.

Answer 60

• ATP7A is needed to release Cu from the enterocyte into the blood.
  
  • Lack of ATP7A leads to impaired release of copper from enterocytes (= decreased absorption → copper deficiency)
• Impaired uptake of copper across blood-brain barrier by the brain which leads to neurological deficits that cannot be corrected.
• Deficiency symptom → implicated metalloenzyme
  
  • Steely depigmented hair → tyrosinase
  • Ruptured arteries → lysyl oxidase
  • Reduced bone mineral density → lysyl oxidase
  • Brain & cognitive abnormalities → decreased synthesis and degradation of neuropeptides due to impaired transport across BBB and also cytochrome C oxidase is important in synthesis of myelin

Question 61

Describe the physiological effects of Wilson’s disease.

Answer 61

• Impaired excretion of copper in bile (= copper toxicity)
• Impaired secretion of ceruloplasmin (= main copper transporter → lower transport in blood despite toxicity)

Question 62

List good food sources of copper.

Answer 62

• Meats (organ meats), shellfish, legumes, nuts, and seeds
• In food → mainly Cu²⁺ bound to a.a./proteins
• In supplements → copper sulfate and other complexed forms

Question 63

Explain the processes involved in copper digestion.

Answer 63

• Release of Cu²⁺ from food components via digestive enzymes in stomach and small intestine
• Reduction of Cu²⁺ → Cu⁺ (main absorption form = Cu⁺)
  
  • Occurs in stomach (low pH) and
  • By reductases in the small intestine

Question 64

Explain the processes involved in copper absorption.

Answer 64

• Where → mainly duodenum
• How → mainly as cuprous (Cu⁺)
  
  • (1) Carrier mediated through Copper transporter 1 (Ctr1) → synthesis may be inversely related to status
  • (2) DMT1
• Overall absorption rate → absorption efficiency inversely related to dietary intakes and body copper status

Question 65

Explain the processes involved in copper transport.

Answer 65

• Intracellular movement of copper via chaperone proteins → prevents pro-oxidant effects of copper; transfers copper to various enzymes
• ATP7A → transport of copper through the basolateral membrane of enterocyte; release of copper from most cells (except liver); transport of copper across blood-brain barrier
• ATP7B → transport of copper into golgi for synthesis of copper containing enzymes & ceruloplasmin; export of copper into bile duct for excretion

Question 66

Explain the processes involved in copper metabolism.

Answer 66

• Shuttled and transferred into Golgi network via ATP7B → incorporation into ceruloplasmin and other copper-metalloenzymes
• With excess copper, ATP7B moves Cu⁺ to vesicles → into bile duct for secretion into intestine
• Storage, bound to metallothionein

Question 67

Explain the processes involved in copper excretion.

Answer 67

• Fecal (95%)
  
  • Biliary excretion as homeostatic mechanism
    
    • Copper bound to bile components, cannot be reabsorbed!
    • Copper excretion into bile involves ATP7B

Question 68

Explain the importance of hepatic metabolism of copper.

Answer 68

• Shuttled and transferred into Golgi network via ATP7B → incorporation into ceruloplasmin and other copper-metalloenzymes
• With excess copper, ATP7B moves Cu⁺ to vesicles → into bile duct for secretion into intestine
• Storage, bound to metallothionein

Question 69

Describe seven functions of copper in the body.

Answer 69

1. Antioxidant function: Cu/Zn superoxide dismutase (SOD)
2. Iron transport: ceruloplasmin and hephaestin
3. Electron transport chain
4. Pigment (melanin) synthesis: tyrosinase
5. Collagen synthesis (in lysyl oxidase)
6. Hormone activation
7. Neurological roles

Question 70

Discuss important nutrient-nutrient interactions for copper. [3]

Answer 70

• High zinc intake stimulates intestinal metallothionein which binds copper and prevents absorption (= zinc induced copper deficiency)
• Copper is needed for iron transport through ceruloplasmin or hephaestin which oxidize iron so that it can bind transferrin
• Vitamin C (a.k.a. ascorbic acid) maintains copper in reduced state for enzyme function

Question 71

Discuss risk factors for developing copper deficiency. [3]

Answer 71

• Menke’s genetic disorder
• High zinc intake
• Impaired absorption (e.g., atrophic gastritis, IBD)

Question 72

Explain the physiological implications of copper deficiency. [4]

Answer 72

• Deficiency symptoms → Cu-metalloenzyme activity
  
  • Anemia → lower hephaestin or ceruloplasmin → lower iron oxidation and transport
  • Weakened bones → decreased lysyl oxidase → decreased collagen and elastin
  • Vascular dysfunction → decreased lysyl oxidase → decreased collagen and elastin which are important in arterial function
  • Depigmentation of skin and hair → decreased tyrosinase which produces melanin → reduced melanin synthesis

Question 73

List methods for assessing copper status.

Answer 73

• No consensus on best biomarker to use → partially because of efficient homeostasis of tissue copper concentrations
• (1) Serum/plasma copper and (2) serum ceruloplasmin → reliable only for severe deficiency; not sensitive enough to detect marginal Cu-deficiency
• (3) Erythrocyte superoxide dismutase activity → more sensitive indicator of copper depletion than serum copper or ceruloplasmin

Question 74

Describe the manifestations of copper toxicity.

Answer 74

• Copper has a UL = 10mg/day
• Acute toxicity → abdominal pain; nausea; vomiting
• Chronic toxicity (rare) → liver damage

Question 75

Answer 75

Answer → B

Question 76

Menke’s is a genetic disorder resulting in copper deficiency.

True or False?

Answer 76

True.

Question 77

Menke’s is a genetic disorder resulting in copper toxicity.

True or False?

Answer 77

False.

Menke’s is a genetic disorder resulting in copper deficiency.

Question 78

Wilson’s is a genetic disorder resulting in copper deficiency.

True or False?

Answer 78

False.

Wilson’s is a genetic disorder resulting in copper toxicity.

Question 79

Wilson’s is a genetic disorder resulting in copper toxicity.

Answer 79

True.

Question 80

Describe the signs of Menke’s disease. [5]

Answer 80

Steely depigmented hair

Ruptured arteries

Reduced BMD

Anemia

Brain & cognitive abnormalities

Question 81

Describe the signs of Wilson’s disease. [2]

Answer 81

Liver disease

Impaired motor control and brain damage if untreated

Question 82

Describe the onset & prognosis of Menke’s disease.

Answer 82

Onset at birth

Poor prognosis with life expectancy <10 years

Question 83

Describe the onset and prognosis of Wilson’s disease.

Answer 83

Onset between 5 - 35 years

With treatment normal & healthy life

Question 84

Chelating agents are a treatment for Menke’s disease.

True or False?

Answer 84

False.

There is no treatment for Menke’s disease

Question 85

Chelating agents are a treatment for Wilson’s disease.

True or False?

Answer 85

True.

Question 86

What is copper, and what is the chemical structure of copper?

Answer 86

Copper is an essential micromineral, or trace element

Occurs in two forms:

Cu²⁺ (cupric)

Cu⁺ (cuprous)

Question 87

What are the DRI for copper and what are they based on?

Answer 87

RDAs for copper

Depletion/repletion studies and on studies estimating obligatory losses of copper over a range of intake allowed the estimation of requirements

Question 88

Answer 88

Answer → A

1 milligram (mg) is equal to 1000 micrograms (μg)

Question 89

The overall absorption rate of copper is directly related to dietary intakes and body copper status.

True or False?

Answer 89

False.

Absorption efficiency of copper is inversely related to dietary intakes and body copper status.

Question 90

Absorption efficiency of copper is inversely related to dietary intakes and body copper status.

True or False?

Answer 90

True.

Question 91

Copper transporter 1 synthesis may be inversely related to copper status.

True or False?

Answer 91

True.

Question 92

Copper transporter 1 synthesis may be directly related to copper status.

True or False?

Answer 92

False.

Copper transporter 1 synthesis may be inversely related to copper status.

Question 93

Answer 93

Answer → D

Legumes, nuts, seeds

Question 94

Describe copper transport from intestine to liver.

Answer 94

• Passage through basolateral membrane via ATP7A, a copper transporting ATPase (= active transport)
• Transport through hepatic portal blood bound to proteins (mostly albumin)
• Liver uptake via multiple carrier proteins, such as Ctr1, Ctr2, DMT1, and other unidentified carriers.

Question 95

What is the role of ATP7A?

Answer 95

• Transport of copper through basolateral membrane of enterocyte
• Release of copper from most cells (except liver)
• Transport of copper across the blood-brain barrier

Question 96

What is the role of ATP7B?

Answer 96

• Transport of copper into golgi for synthesis of copper containing enzymes & ceruloplasmin
• Export of copper into bile duct for excretion

Question 97

What is ceruloplasmin?

Answer 97

• Secreted from liver
• Main transporter of copper in blood plasma

Question 98

Briefly describe the cellular uptake, transport, and metabolism of copper. [4]

Answer 98

• Uptake of ceruloplasmin into tissues via receptors
• In cells, bound to chaperone proteins
• Use for: biochemical needs, storage, or transport out
• Release of copper from cells via ATP7A (expressed in most body cells, except liver)

Question 99

Where is the main site for copper storage and controlling copper homeostasis?

Answer 99

Liver

Question 100

Describe the storage of copper.

Answer 100

• Bound to metallothionein
  
  • Copper influences hepatic, renal, and brain metallothionein synthesis, but not intestinal metallothionein synthesis.

Question 101

Copper influences hepatic, renal, and brain metallothionein synthesis, but not intestinal metallothionein synthesis.

True or False?

Answer 101

True.

Question 102

Copper influences hepatic, renal, brain, and intestinal metallothionein synthesis.

True or False?

Answer 102

False.

Copper influences hepatic, renal, and brain metallothionein synthesis, but not intestinal metallothionein synthesis.

Question 103

Answer 103

Answer → C

Question 104

Describe the antioxidant function of copper.

Answer 104

Cu/Zn superoxide dismutase (SOD)

Question 105

Describe the role of copper in iron transport.

Answer 105

Ceruloplasmin (= liver) and hephaestin (= basolateral membrane) → oxidation of iron, which is required for cellular iron release and binding to transferrin

• Ceruloplasmin is also important for:
  
  • Transport of copper in plasma
  • Antioxidant - important in inflammatory process

Question 106

Describe the role of copper in the electron transport chain.

Answer 106

Cytochrome c oxidase = terminal oxidation step in ETC

Question 107

Describe the role of copper in pigment synthesis.

Answer 107

Melanin synthesis → tyrosinase

Question 108

Describe the role of copper in collagen & elastin synthesis.

Answer 108

Via lysyl oxidase

• Iron and vitamin C required for hydroxylase
• Copper required for lysyl oxidase → cross-linking of tissue proteins

Question 109

Describe the role of copper in hormone activation.

Answer 109

Cu required for amidation of peptide hormones → crucial for hormone function

Hormones include: gastrin, cholecystokinin, calcitonin, thyrotropin, vasopressin, etc.

Question 110

Describe why suboptimal copper status may result in neurological and physiological manifestations [3].

Answer 110

• Biogenic amine degradation (in amine oxidases)
  
  • Including histamine, dopamine, serotonin, norepineprhine
• Norepinephrine synthesis (dopamine monooxygenase)
• Cytochrome C oxidase is important in synthesis of myelin.

Question 111

Answer 111

Answer → D

Question 112

Describe the prevalence of copper deficiency.

Answer 112

Rare in adults → more likely with high Zn intake (>40mg/day) or conditions/medications that reduce Cu absorption

Question 113

Answer 113

Answer → B

Question 114

Compare the lab findings of Menke’s vs Wilson’s disorder.

Answer 114

• ATP7B is required for secretion of ceruloplasmin from liver, deficiency decreases its concentration → inability to secrete it means the liver will store more with metallothionein

Question 115

Copper does not have a UL.

True or False?

Answer 115

False.

Copper UL = 10mg/day

Question 116

Copper has a UL.

True or False?

Answer 116

True.

Copper UL = 10mg/day

Question 117

Discuss the physiological implications of vitamin C deficiency. [7]

Answer 117

Scurvy → first vitamin deficiency to be prevented (1753 ‘Treatise on the Scurvy’)

• Fatigue and weakness → may be related to reduced carnitine synthesis
• Impaired collagen synthesis leading to: [5]
  
  • Small, red skin discolouration caused by ruptured small blood vessels
  • Easy bruising
  • Swollen, bleeding, necrotic gums
  • Loose decaying teeth
  • Impaired wound healing
• Fatal, if untreated
• Development of scurvy in as little as 1 month!

Question 118

Discuss risk factors for vitamin C deficiency. [3]

Answer 118

1. Inadequate intake → limited food variability
2. Smoking (accelerates the depletion of the body’s ascorbic acid pool) → smokers need more vitamin C
3. Certain diseases
   
   1. GI diseases/conditions that cause malabsorption
   2. Some types of cancer → increased vitamin C turnover
   3. Diabetes → increased urinary excretion

Question 119

List the forms of vitamin C.

Answer 119

• Vitamin C = ascorbic acid (reduced & active form)
• Dehydroascorbic acid (oxidized form → can be reduced to ascorbic acid)
• No endogenous synthesis of vitamin C in humans (cats can synthesize it!)

Question 120

Describe the functions of vitamin C. [7]

Answer 120

1. Antioxidant activity → neutralizes ROS
2. Co-substrate for enzymes/reducing agent [4]
   
   1. Collagen synthesis
   2. Carnitine synthesis
   3. Neurotransmitter synthesis
   4. Hormone synthesis
3. Other functions [2]
   
   1. Possible role in gene expression
   2. Enhances immune function

Question 121

Discuss nutrient-nutrient interactions for vitamin C.

Answer 121

1. Vitamin C and iron & copper interactions
   
   1. Vitamin C = reducing agent
   2. Vitamin C enhances the intestinal absorption of non-heme iron (Fe³⁺) and copper by reducing them into appropriate oxidation state for absorption, i.e., Fe²⁺, Cu⁺
2. Vitamin C and vitamin E & niacin
   
   1. Vitamin C = reducing agent

Question 122

List the main food sources of vitamin C and its forms.

Answer 122

• Food sources → fruits and vegetables
• Forms in food → ascorbic acid (main), dehydroascorbic acid
• Forms in supplements → ascorbic acid, calcium ascorbate, sodium ascorbate, dehydroascorbate → absorption does not appear to differ between forms

Question 123

Explain the processes involved in vitamin C digestion.

Answer 123

None required!

Question 124

Explain the processes involved in vitamin C absorption.

Answer 124

• Where → small intestine, especially proximal jejunum
• How
  
  • (1) Ascorbic acid → sodium-dependent vitamin C transporters (SVCT1 and SVCT2) → SVCT1 = main → down-regulated by vitamin C
  • (2) Dehydroascorbic acid → glucose transporters (GLUT)
• In enterocyte → rapid reduction of dehydroascorbic acid → ascorbic acid
• From enterocyte → ascorbic acid diffuses through ion channels in the basolateral membrane → capillaries → hepatic portal vein → liver (just like other water-soluble vitamins)

Question 125

Explain the processes involved in vitamin C transport.

Answer 125

• Transport of vitamin C from liver to extrahepatic tissues → in free form in blood as ascorbic acid (main) or dehydroascorbic acid (minor)
• Cellular uptake/tissue uptake
  
  • Ascorbic acid via SVCT1 and SVCT2
  • Dehydroascorbic acid via GLUTs (i.e., glucose transporters) → reduced intracellularly to ascorbic acid via glutathione-dependent reductase

Question 126

Explain the processes involved in vitamin C metabolism.

Answer 126

• Oxidized to dehydroascorbic acid
• Further metabolized to oxalic acid and other products
  
  • Oxalic acid contributes to formation of kidney stones → at high intakes

Question 127

Explain the processes involved in vitamin C excretion.

Answer 127

• Excretion through urine
• Intact or catabolized, depending on level of vitamin C intake and status
• Reabsorbed through SVCT1
• When SVCT1 in renal tubules saturated = upper limit of renal absorption

Question 128

Describe the manifestations of excess vitamin C.

Answer 128

• No serious adverse effects
• Most common symptoms:
  
  • Diarrhea
  • Nausea
  • Abdominal cramps
  • Other GI disturbances → due to the osmotic effect of unabsorbed vitamin C in the GI tract
• Tolerable Upper Intake Level (UL) for vitamin C = 2000mg/day (2g/day) for adults

Question 129

Discuss whether high-dose vitamin C supplements can prevent or treat cold symptoms.

Answer 129

Clinical evidence:

• No benefit of pharmacological doses >1-2 g per day
• Regular use does not prevent colds
• Regular usage (≤ 1 g/day) may decrease the duration and severity of symptoms
• Regular use may decrease incidence of colds in individuals under extreme physical stress (e.g., marathon runners, soldiers exposed to extreme temperatures, etc.)
• Note → intravenous vitamin C is often used when people are hospitalized to mitigate cytokine storms

Question 130

Jessica, a 22 year old female, eats a wide variety of foods, does not smoke or consume alcohol, and describes herself as generally healthy. Jessica is very worried about getting sick as she ‘cannot afford to miss work’. She decides to start taking a vitamin C supplement as she heart these may help prevent colds and hopes they may help keep her healthy through the pandemic.

Answer 130

Answer → C

Question 131

Jessica, a 22 year old female, eats a wide variety of foods, does not smoke or consume alcohol, and describes herself as generally healthy. Jessica is very worried about getting sick as she ‘cannot afford to miss work’. She decides to start taking a vitamin C supplement as she heart these may help prevent colds and hopes they may help keep her healthy through the pandemic.

Answer 131

Answer → C

Question 132

Jessica, a 22 year old female, eats a wide variety of foods, does not smoke or consume alcohol, and describes herself as generally healthy. Jessica is very worried about getting sick as she ‘cannot afford to miss work’. She decides to start taking a vitamin C supplement as she heart these may help prevent colds and hopes they may help keep her healthy through the pandemic.

Answer 132

Answer → D

Question 133

Jessica, a 22 year old female, eats a wide variety of foods, does not smoke or consume alcohol, and describes herself as generally healthy. Jessica is very worried about getting sick as she ‘cannot afford to miss work’. She decides to start taking a vitamin C supplement as she heart these may help prevent colds and hopes they may help keep her healthy through the pandemic.

Answer 133

Answer → B

Question 134

Jessica, a 22 year old female, eats a wide variety of foods, does not smoke or consume alcohol, and describes herself as generally healthy. Jessica is very worried about getting sick as she ‘cannot afford to miss work’. She decides to start taking a vitamin C supplement as she heart these may help prevent colds and hopes they may help keep her healthy through the pandemic.

Answer 134

Answer → C

Question 135

Describe the antioxidant activity of vitamin C.

Answer 135

• Powerful antioxidant/reducing agent, providing H⁺/e^-
• By providing H⁺/e^-, ascorbic acid neutralizes ROS
• Regeneration of other antioxidants, e.g., vitamin E and glutathione

Question 136

Describe vitamin C as a co-substrate for enzymes and as a reducing agent.

Answer 136

• Vitamin C functions as a reducing agent to maintain metal ions (copper and iron) in reduced state in metalloenzymes.
• Co-substrate for enzymes in:
  
  • Collagen synthesis → requires iron and copper as cofactors; vitamin C regenerates their reduced forms
  • Carnitine synthesis → requires iron; vitamin C regenerates reduced form → important for amino acid metabolism
    
    • Carnitine plays a critical role in energy production. It transports long-chain fatty acids into the mitochondria so they can be oxidized (“burned”) to produce energy. It also transports the toxic compounds generated out of this cellular organelle to prevent their accumulation.
• Hormone synthesis e.g., gastrin cholecystokinin, calcitonin, vasopressin, etc. → copper is required; vitamin C regenerates its reduced form

Question 137

Describe roles of vitamin C unrelated to its antioxidant capacity, reducing agent, or co-substrate roles.

Answer 137

• Enhances immune function → mechanisms unclear but may involve its antioxidant capacity, as well as:
  
  • Increased production and activity of immune cells
  • Promoting chemotaxis (i.e., recruitment of immune cells to sites of infection)
  • Increased production of complement proteins

Question 138

Describe the stability of vitamin C.

Answer 138

Stability → destroyed by heat, light, oxidation and pH > 7; stable at pH < 7

Question 139

Describe the DRI for vitamin C.

Answer 139

RDAs (mg/day) → 75 mg/day for me

Based on estimations to nearly maximize tissue concentrations and minimize urinary excretion → smokers recommended to take additional 35mg vitamin C daily

Question 140

Describe the overall absorption rate of vitamin C.

Answer 140

• Absorption efficiency is dose-dependent = absorption rate is inversely related with the intake level:
  
  • 70-95% at normal range (30-180 mg/day)
  • 98% at <20mg
  • ~50% at >1g
  • 16% at 12g
    
    • Regulated through transporter in brush border membrane → SVCT1
• Relevance of reducing absorption efficiency with increasing intake
  
  • Prevention of symptoms of excess → protect against toxicity
  • Avoidance of symptoms of deficiency

Question 141

Because there are no serious adverse effects to excess intake, vitamin C does not have a UL.

True or False?

Answer 141

False!

UL = 2000mg/day

Common symptoms:

• Diarrhea
• Nausea
• Abdominal cramps
• Other GI disturbances

Question 142

Vitamin C has a UL because excess intake is associated with serious adverse effects.

True or False?

Answer 142

False.

Vitamin C has a UL (2000mg/day) because of common symptoms (e.g., diarrhea, nausea, abdominal cramps, GI distress)

Question 143

Discuss vitamin C in relation to cancer & CVD.

Answer 143

• Evidence from correlational studies:
  
  • Increased intakes of fruits/vegetables → decreased risk of cancer and CVD
  • Proposed mechanism:
    
    • Vitamin C can limit the formation of carcinogens, modulate immune response, and attenuate oxidative damage that can lead to cancer and CVD
• Evidence from clinical trials:
  
  • No protective or therapeutic benefits of vitamin C

Question 144

Jessica, a 22 year old female, eats a wide variety of foods, does not smoke or consume alcohol, and describes herself as generally healthy. Jessica is very worried about getting sick as she ‘cannot afford to miss work’. She decides to start taking a vitamin C supplement as she heart these may help prevent colds and hopes they may help keep her healthy through the pandemic.

Answer 144

Answer → B

It may reduce the duration and severity, but it will not prevent colds.

Question 145

Explain the processes involved in vitamin C storage.

Answer 145

No appreciable storage of vitamin C in the body as it is a water-soluble organic compound.

Question 146

Which form of vitamin C has antioxidant activity?

Answer 146

Ascorbic acid

Question 147

List the forms of vitamin E.

Answer 147

• Vitamin E encompasses 8 compounds/vitamers → 2 classes each with 4 forms
• Classes:
  
  • Tocopherols with saturated side-chains
  • Tocotrienols with unsaturated side-chains
• Forms per class → differ in the number and location of the methyl group on the chromanol ring
  
  • α
  • β
  • γ
  • δ
• Different forms are NOT interconvertible
• α-tocopherol is the main biologically active form

Question 148

Describe the chiral centres of tocopherols.

Answer 148

• Tocopherols contain 3 chiral centres with a configuration of R or S (used to designate stereoisomers of asymmetrical molecules like vitamin E)
• Naturally occurring and most biologically active form = RRR-α-tocopherol
• 2R-stereoisomeric forms (RSR-, RRS-, RSS-) of α-tocopherol have some activity
• 2S-stereoisomeric forms (SSR-, SSR-, SRS-, SSS-) disappear rapidly from plasma and have very little activity

Question 149

List good food sources of vitamin E as well as the forms it takes.

Answer 149

• In food → various forms, but α-tocopherol is the one retained in the body
• Food sources → primarily found in plant foods, especially nuts, seeds, and oils; animal products are inferior
• In supplements and fortified foods → all-racemic α-tocopherol (i.e., all possible stereoisomers of α-tocopherol): α-tocopheryl acetate or α-tocopheryl succinate

Question 150

Explain the processes involved in vitamin E digestion.

Answer 150

• None for tocopherols
• Hydrolysis of synthetic tocopherol esters by esterases from pancreas and small intestine

Question 151

Explain the processes involved in vitamin E absorption.

Answer 151

• Where → jejunum
• How → micelle formation with dietary fat and bile salts; diffusion of micelles across brush border membrane
• Simultaneous ingestion of dietary fats improves absorption of vitamin E.

Question 152

Explain the processes involved in vitamin E transport.

Answer 152

• Enterocyte → incorporation into chylomicrons → passage through basolateral membrane → into lymphatic system → blood circulation at thoracic duct
• Uptake of chylomicron content → lipoprotein lipase → hydrolysis of chylomicrons → release of fatty acids and vitamin E for uptake
• Chylomicron remnants contain various vitamin E forms → transported to liver
• In liver → hepatic metabolism occurs specific to α-tocopherol → incorporation of α-tocopherol into VLDL by α-tocopherol transfer protein (α-TTP) → release into blood
  
  • Other forms → metabolized for excretion
    
    • Tissue uptake of α-tocopherol from VLDL, LDL, and HDL.

Question 153

Explain the processes involved in vitamin E storage.

Answer 153

• 90% in an unesterified form in fat droplets in adipose tissue → however, this is released slowly and does not represent an available source of vitamin E when intakes are low

Question 154

Explain the processes involved in vitamin E metabolism.

Answer 154

• Catabolized by the liver
• α-tocopherol incorporated into VLDL by α-TTP & released into blood

Question 155

Explain the processes involved in vitamin E excretion.

Answer 155

Excreted in bile (feces) and urine

Question 156

Describe the metabolic functions of vitamin E.

Answer 156

• Main function = antioxidant
  
  • Functions in interior of membranes → vitamin E is fat-soluble
  • Protects membranes from lipid peroxidation
  • The radical form is not destructive due to the aromatic ring structure stabilizing the charge
• Other functions, less characterized
  
  • Interaction with cell receptors and signalling molecules (e.g., inhibits protein kinase C)
  • Regulation of gene expression

Question 157

Discuss the nutrient-nutrient interactions for vitamin E. [4]

Answer 157

• Selenium and vitamin E interaction
  
  • Selenium required for glutathione peroxidase (= enzyme that converts lipid peroxides into lipid alcohols)
  • Complementary action of both nutrients → therefore, lower intakes of selenium puts higher demands on vitamin E and vice versa.
• Vitamin C and vitamin E interaction
  
  • Vitamin C regenerates vitamin E after termination of lipid peroxidation step
• Polyunsaturated fatty acids and vitamin E interaction
  
  • Requirement for vitamin E increases/decreases as degree of unsaturation of fatty acids in body tissue rises/falls
    
    • Luckily, foods high in PUFA are also relatively good sources of vitamin E.
• Fat-soluble vitamins and vitamin E interaction → A, E, and K (D does not interfere as much)
  
  • Vitamin E inhibits β-carotene absorption and metabolism in the intestine
  • Vitamin E impairs vitamin K absorption and metabolism.

Question 158

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

Answer 158

• Prevalence = rare in adults
• (1) Diseases/conditions that cause fat malabsorption
  
  • Cystic fibrosis
  • Chronic cholestasis (decreased bile production)
• (2) Genetic defects
  
  • Lipoprotein disorders
  • α-tocopherol transfer protein (α-TTP)

Question 159

Explain the physiological implications of vitamin E deficiency. [3]

Answer 159

• Vitamin E functions to maintain the integrity of cell membranes
• Symptoms:
  
  • Fragile red blood cells = hemolytic anemia (RBCs lyse due to lack of vitamin E to protect their cell membranes)
  • Degeneration of nerve cells and effects on muscle = peripheral neuropathy (pain/numbness in extremities); ataxia (poor muscle coordination); skeletal muscle pain; weakness
  • Skin: ceroid pigments (oxidized proteins and fats) accumulate and appear as brown spots

Question 160

Describe the manifestations of excess vitamin E.

Answer 160

• Increased tendency for bleeding/impaired blood coagulation (due to impaired vitamin K absorption and RBC lysis)
• Gastrointestinal distress including nausea, diarrhea, flatulence

Question 161

Answer 161

Answer → B

The carbon at position 2 is bound to 4 different groups.

Question 162

Explain why the EAR are based on α-tocopherol only. [3]

Answer 162

• (1) α-tocopherol is the only form of vitamin E maintained in plasma, and the only form that contributes to vitamin E activity
  
  • Because of preferential binding to α-tocopherol transfer protein (α-TTP), which is necessary for secretion of vitamin E from the liver
• (2) Only 2R-stereoisomers of α-tocopherol appear to have any activity.
  
  • 2S-stereoisomers disappear rapidly from blood and do not have significant vitamin E activity.
• (3) Body is unable to interconvert the different forms of vitamin E.

Question 163

Describe the DRI for vitamin E.

Answer 163

• Current recommendations → in units of mg alpha-tocopherol
  
  • 1mg vitamin E = 1 mg RRR-alpha-tocopherol or 2 mg all rac-alpha-tocopherol
• Based on induced deficiency in humans and the correlation between H₂O₂-induced erythrocyte lysis and plasma alpha-tocopherol concentrations
• Note
  
  • EAR and RDA based on the 2R-stereoisomeric forms of alpha-tocopherol
  • UL based on all 8 stereoisomeric forms of alpha-tocopherol

Question 164

All racemic α-tocopherol refers to the synthetic form that contains all of the stereoisomers of α-tocopherol.

How many stereoisomers of α-tocopherol are there?

Answer 164

8

RRR, RSR, RSS, RRS, SSS, SSR, SRS, SRR

Question 165

All racemic alpha-tocopherol refers to the synthetic form that contains all of the stereoisomers of alpha tocopherol.

How many of the stereoisomers of alpha-tocopherol have biological activity in the body?

Answer 165

4

RRR, RSR, RSS, RRS

Question 166

All racemic α-tocopherol refers to the synthetic form that contains all of the stereoisomers of α- tocopherol.

What proportion of all-racemic α-tocopherol has biological activity in the body?

Answer 166

50%

Question 167

Answer 167

Answer → C

Vitamin E is mostly found in plant oils. A low fat diet would exclude these sources.

Question 168

Answer 168

Answer → B

We absorb all the different forms, and many forms are deposited throughout the body. Once the chylomicron remnant reaches the liver, other non-biological forms are metabolized and excreted from the body.

Question 169

Describe how lipid peroxidation can be interrupted by vitamin E.

Answer 169

• Initiation → lipid (PUFA) reacts with free radical generating lipid carbon centered radical (alkyl radical)
• Propagation → Alkyl radical reacts with oxygen to form lipid peroxyl radical which then reacts with another lipid to form another alkyl radical → chain reaction continues unless interrupted
• Termination → vitamin E reduces lipid peroxyl radical and alkyl radical, ending the chain of oxidation
  
  • Vitamin E becomes an α-tocopherol radical → regenerated by vitamin C

Question 170

How is vitamin E function restored after interrupting lipid oxidation?

Answer 170

Regeneration by vitamin C.

Question 171

Answer 171

Answer → A

Higher intakes of PUFA means more UFA inside cells → more prone to oxidation → more vitamin E is necessary to interrupt the chain reaction

Question 172

Vitamin E does not have a UL.

True or False?

Answer 172

False.

Vitamin E has a UL = 1,000mg/day

Applies to all supplemental forms of alpha-tocopherol

• Symptoms of excess
  
  • Increased tendency for bleeding/impaired blood coagulation (due to impaired vitamin K absorption and RBC lysis)
  • Gastrointestinal distress including nausea, diarrhea, flatulence

Question 173

Vitamin E has a UL.

True or False?

Answer 173

True.

UL = 1,000mg/day

• Symptoms of excess:
  
  • Increased tendency for bleeding/impaired blood coagulation (due to impaired vitamin K absorption and RBC lysis)
  • Gastrointestinal distress including nausea, diarrhea, flatulence

Question 174

Answer 174

Answer → A

Question 175

How are dietary vitamin E requirements estimated?

Answer 175

• Intakes of RRR-α-tocopherol and other 2R-stereoisomers of α-tocopherol are considered
• Other forms, although absorbed, do not contribute to requirements.

Question 176

Define vitamin A and list forms of vitamin A and carotenoids.

Answer 176

Vitamin A = a group of compounds that possess the biological activity of retinol (in present form or after conversion)

Includes:

• Retinoids → retinol, retinal, retinoic acid, and retinyl esters
  
  • a.k.a. pre-formed vitamin A
• Provitamin A carotenoids → β-carotene (highest provitamin A activity), α-carotene, and β-cryptoxanthin
  
  • Carotenoids can be converted to vitamin A.
  • Note β-carotene is essentially two retinol molecules

Question 177

Explain why dietary recommendations for vitamin A are listed as RAE.

Answer 177

RAE = retinol activity equivalent → conversion factor defined for estimation of EAR for vitamin A

Question 178

List dietary sources for vitamin A and carotenoids.

Answer 178

• Animal sources → retinyl esters
  
  • Beef liver, herring, milk, egg
• Plant sources → carotenoids
  
  • Spinach, carrots, collards, cantaloupe, sweet potato

Question 179

Explain the process of vitamin A/carotenoid digestion.

Answer 179

• Protein-bound carotenoids and retinyl esters hydrolyzed by pepsin and other proteases → carotenoids and retinyl esters hydrolyzed by hydrolases, esterases, and lipases → free carotenoids and free retinol
• Fatty acids, phospholipids. monoacylglycerol, and cholesterol emulsified with bile and incorporated into micelles with free carotenoids and free retinol for absorption via passive diffusion across the brush border membrane.

Question 180

Explain the process of vitamin A/carotenoid absorption.

Answer 180

• Vitamin A → 70-90% absorbed as long as the meal contains some (~10g) fat
• Carotenoids → <5% for carotenoids in uncooked vegetables or non-heat-processed juice; ~60% if present as pure oil or as part of a supplement
• Fiber → especially pectin; interferes with micelle formation

(1) Micelles deliver carotenoids (including beta-carotene) and retinol to the intestinal cell, where they are absorbed by passive diffusion.

(2) Beta-carotene is converted to 2 retinol

(3) Retinol (from diet and conversion from beta-carotene) is converted to retinyl ester (storage form of vitamin A)

(4) Retinyl esters + carotenoids are incorporated into chylomicrons with other lipids and enter the lymphatic and then blood circulation

Question 181

Explain the process of vitamin A/carotenoid transport from the enterocyte.

Answer 181

• Chylomicrons enter lymph, then the bloodstream via the thoracic duct and deliver retinyl esters & carotenoids to extrahepatic tissues (i.e., muscle, lungs, adipose tissue)
• Chylomicron remnants deliver remainder of retinyl esters & carotenoids to the liver

Question 182

Explain the process of vitamin A/carotenoid storage.

Answer 182

• Once hepatic storage capacity is exceeded, toxicity may occur
• Retinol (from diet and conversion from beta-carotene) is converted to retinyl ester (= storage form of vitamin A)

Question 183

Explain the process of vitamin A/carotenoid metabolism.

Answer 183

• Retinol and retinal/retinoic acid
  
  • Oxidized to various metabolites
  • Metabolites (water soluble) excreted in urine (60%)
  • Some metabolites are secreted into bile for fecal excretion (40%)

Question 184

Explain the process of vitamin A/carotenoid excretion.

Answer 184

• Retinol and retinal/retinoic acid
  
  • Oxidized to various metabolites
  • Metabolites (water soluble) excreted in urine (60%)
  • Some metabolites are secreted into bile for fecal excretion (40%)

Question 185

Explain factors influencing bioavailability of vitamin A/carotenoids. [4]

Answer 185

1. Dietary fat → needed for absorption of vitamin A
2. Heat → cooking improves the bioavailability of carotenoids
3. Fibre → especially pectin → interferes with micelle formation and absorption
4. Protein → needed for converting beta-carotene to retinol and for transport of vitamin A

Question 186

What is the role of vitamin A binding proteins?

Answer 186

• Vitamin A, as a fat-soluble vitamin, is transported within cells and in the circulation bound to proteins
• Circulating form = retinol-RBP-transthretin complex → a.k.a. prealbumin
• In cells:
  
  • Retinol binds to cellular retinol-binding proteins (CRBPs)
  • Retinoic acid binds to cellular retinoic acid-binding proteins (CRABPs)

Question 187

Describe nutrient-nutrient interactions for vitamin A.

Answer 187

1. Dietary fat → needed for absorption of vitamin A
2. Protein → needed for converting beta-carotene to retinol and for transport of vitamin A
3. Vitamin E and vitamin K → excess vitamin A intake can lower the bioavailability of vitamin E and K.

Question 188

Discuss the prevalence of and risk factors [2] for developing vitamin A deficiency.

Answer 188

• Less common in developed countries
• Increased risk
  
  • Fat malabsorption disorders (e.g., cystic fibrosis, IBD)
  • Protein deficiency

Question 189

Explain the physiological implications of vitamin A deficiency. [7]

Answer 189

• Night blindness
• Xerophthalmia
• Anorexia
• Impaired growth
• Obstruction and enlargement of hair follicles
• Keratinization of epithelial cells (skin)
• Increased susceptibility to infections

Question 190

Describe the metabolic functions of vitamin A and carotenoids.

Answer 190

• Retinoids
  
  • Vision
  • Roles related to regulation of gene expression:
    
    • Cellular differentiation, proliferation and growth
    • Immune system
    • Reproduction
    • Bone development
• Carotenoids
  
  • Potent antioxidant → presence of conjugated double bonds
  • Eye health
  • Protects against:
    
    • Heart disease
    • Cancer
    • Macular degeneration
    • Cataracts

Question 191

Describe the manifestations of excess vitamin A.

Answer 191

• Once hepatic storage capacity for retinol is exceeded, toxicity may occur:
  
  • Acute → GI effect (e.g., nausea), headache
  • Chronic → liver abnormalities; reduced bone mineral density; bone and joint pain
  • Teratogenic → miscarriage; birth defects; permanent learning disabilities
• UL = 3000ug preformed vitamin A

Question 192

Colleen is a 34-year-old female. She has come to see her doctor because she has noticed her night vision deteriorating over the past few months and she is now unable drive in the dark. She does not recall any relevant injury or illness occurring prior to this. She does mention that she has been extremely stressed at work and because of this she has not been eating very much, sometimes only eating a few (typically high carbohydrate) snacks on her way to and from work. She has frequent colds, which she attributes to her lack of sleep, but otherwise does not have any current health or genetic disorders. The physical exam reveals that Colleen is currently underweight (BMI 17 kg/m2) and has very dry and scaly skin on her arms and legs. Her dietary analysis indicates that she is well below the EAR for vitamin A and her total calories are also low, with particularly low intakes of both fat and protein. Her doctor suspects a vitamin A deficiency and this is confirmed with lab findings of a serum vitamin A of 0.58 μmol/L.

Answer 192

Answer → D

Vitamin A = a group of compounds that possess the biological activity of retinol (in present form or after conversion)

Includes:

• Retinoids → retinol, retinal, retinoic acid, and retinyl esters
• Provitamin A carotenoids → β-carotene (highest vitamin A activity), α-carotene, and β-cryptoxanthin

Question 193

Colleen is a 34-year-old female. She has come to see her doctor because she has noticed her night vision deteriorating over the past few months and she is now unable drive in the dark. She does not recall any relevant injury or illness occurring prior to this. She does mention that she has been extremely stressed at work and because of this she has not been eating very much, sometimes only eating a few (typically high carbohydrate) snacks on her way to and from work. She has frequent colds, which she attributes to her lack of sleep, but otherwise does not have any current health or genetic disorders. The physical exam reveals that Colleen is currently underweight (BMI 17 kg/m2) and has very dry and scaly skin on her arms and legs. Her dietary analysis indicates that she is well below the EAR for vitamin A and her total calories are also low, with particularly low intakes of both fat and protein. Her doctor suspects a vitamin A deficiency and this is confirmed with lab findings of a serum vitamin A of 0.58 μmol/L.

Answer 193

Answer → D

5000mcg / (12mcg/RAE) = ~417

2000mcg/ (24mcg/RAE) = ~83

Total = 500 RAE

Answer → No

Question 194

Colleen is a 34-year-old female. She has come to see her doctor because she has noticed her night vision deteriorating over the past few months and she is now unable drive in the dark. She does not recall any relevant injury or illness occurring prior to this. She does mention that she has been extremely stressed at work and because of this she has not been eating very much, sometimes only eating a few (typically high carbohydrate) snacks on her way to and from work. She has frequent colds, which she attributes to her lack of sleep, but otherwise does not have any current health or genetic disorders. The physical exam reveals that Colleen is currently underweight (BMI 17 kg/m2) and has very dry and scaly skin on her arms and legs. Her dietary analysis indicates that she is well below the EAR for vitamin A and her total calories are also low, with particularly low intakes of both fat and protein. Her doctor suspects a vitamin A deficiency and this is confirmed with lab findings of a serum vitamin A of 0.58 μmol/L.

Answer 194

Answer → E

Question 195

Colleen is a 34-year-old female. She has come to see her doctor because she has noticed her night vision deteriorating over the past few months and she is now unable drive in the dark. She does not recall any relevant injury or illness occurring prior to this. She does mention that she has been extremely stressed at work and because of this she has not been eating very much, sometimes only eating a few (typically high carbohydrate) snacks on her way to and from work. She has frequent colds, which she attributes to her lack of sleep, but otherwise does not have any current health or genetic disorders. The physical exam reveals that Colleen is currently underweight (BMI 17 kg/m2) and has very dry and scaly skin on her arms and legs. Her dietary analysis indicates that she is well below the EAR for vitamin A and her total calories are also low, with particularly low intakes of both fat and protein. Her doctor suspects a vitamin A deficiency and this is confirmed with lab findings of a serum vitamin A of 0.58 μmol/L.

Answer 195

• Add a fat source (e.g., oil)
• Add heat (e.g., cook the carrot to help release the vitamin A from the food matrix)
• Remove the apple (i.e., the pectin will reduce absorption)
• Add a protein source (not necessarily important for absorption, but is important for transport)

Question 196

Colleen is a 34-year-old female. She has come to see her doctor because she has noticed her night vision deteriorating over the past few months and she is now unable drive in the dark. She does not recall any relevant injury or illness occurring prior to this. She does mention that she has been extremely stressed at work and because of this she has not been eating very much, sometimes only eating a few (typically high carbohydrate) snacks on her way to and from work. She has frequent colds, which she attributes to her lack of sleep, but otherwise does not have any current health or genetic disorders. The physical exam reveals that Colleen is currently underweight (BMI 17 kg/m2) and has very dry and scaly skin on her arms and legs. Her dietary analysis indicates that she is well below the EAR for vitamin A and her total calories are also low, with particularly low intakes of both fat and protein. Her doctor suspects a vitamin A deficiency and this is confirmed with lab findings of a serum vitamin A of 0.58 μmol/L.

Answer 196

1. Dietary fat → needed for absorption of vitamin A; low fat = low absorption
2. Protein → needed for converting beta-carotene to retinol and for transport of vitamin A; low protein = low transport/utilization

Question 197

Colleen is a 34-year-old female. She has come to see her doctor because she has noticed her night vision deteriorating over the past few months and she is now unable drive in the dark. She does not recall any relevant injury or illness occurring prior to this. She does mention that she has been extremely stressed at work and because of this she has not been eating very much, sometimes only eating a few (typically high carbohydrate) snacks on her way to and from work. She has frequent colds, which she attributes to her lack of sleep, but otherwise does not have any current health or genetic disorders. The physical exam reveals that Colleen is currently underweight (BMI 17 kg/m2) and has very dry and scaly skin on her arms and legs. Her dietary analysis indicates that she is well below the EAR for vitamin A and her total calories are also low, with particularly low intakes of both fat and protein. Her doctor suspects a vitamin A deficiency and this is confirmed with lab findings of a serum vitamin A of 0.58 μmol/L.

Answer 197

• Nightblindness → vitamin A (cis-retinal) is needed for rhodopsin for light detection in rod cells, which are important for ability to see in low light conditions
• Dry, scaly skin → related to vitamin A’s role in cellular differentiation, proliferation, and growth
• Frequent colds → suppressed immune system and increased susceptibility to infections

Question 198

Colleen is a 34-year-old female. She has come to see her doctor because she has noticed her night vision deteriorating over the past few months and she is now unable drive in the dark. She does not recall any relevant injury or illness occurring prior to this. She does mention that she has been extremely stressed at work and because of this she has not been eating very much, sometimes only eating a few (typically high carbohydrate) snacks on her way to and from work. She has frequent colds, which she attributes to her lack of sleep, but otherwise does not have any current health or genetic disorders. The physical exam reveals that Colleen is currently underweight (BMI 17 kg/m2) and has very dry and scaly skin on her arms and legs. Her dietary analysis indicates that she is well below the EAR for vitamin A and her total calories are also low, with particularly low intakes of both fat and protein. Her doctor suspects a vitamin A deficiency and this is confirmed with lab findings of a serum vitamin A of 0.58 μmol/L.

Answer 198

Answer → A

• Teratogenic toxicity
  
  • May lead to miscarriage
  • Effects on the fetus/child
  • Birth defects (e.g., cleft palate)
  • permanent learning disabilities

Question 199

All carotenoids are consumed in the diet.

True or False?

Answer 199

False.

>700 carotenoids in total, but only 60 are consumed in the diet

Examples of non-vitamin A precursor carotenoids:

• Lycopene, zeaxanthin, lutein
• No vitamin A activity, but may have other important physiological functions

Question 200

Not all carotenoids are consumed in the diet.

True or False?

Answer 200

True.

>700 carotenoids in total, but only 60 are consumed in the diet.

Examples of non-vitamin A precursor carotenoids:

• Lycopene, zeaxanthin, lutein
• No vitamin A activity, but may have other important physiological functions

Question 201

Describe the conversion of provitamin A carotenoids to vitamin A.

Answer 201

β-carotene → 2 retinal → retinol or retinoic acid

• Not all β-carotene converted to retinal → 1 β-carotene does not necessarily = 2 RAL
  
  • Up to 15% of β-carotene escaped cleavage
  • Non-central cleavage → produces various alcohols and aldehydes

Question 202

Answer 202

Answer → A

Question 203

Describe the fates of vitamin A in the liver. [4]

Answer 203

In the liver vitamin A (retinol) is:

1. Used as retinoic acid in regulation of gene expression
2. Stored as retinyl esters
3. Excreted with bile
4. Secreted bound to retinol binding protein (RBP) which joins with transthyretin (TTR) to circulate retinol as a tri-molecular complex

Question 204

Describe vitamin A transport and tissue uptake when vitamin A intake is in excess and serum retinol concentrations increase to levels > normal range.

Answer 204

• When vitamin A intake is in excess and serum retinol concentrations increase to levels > normal range:
  
  • Retinol is no longer transported exclusively by RBP
  • Carried by plasma lipoproteins → When retinol is presented in this form to the cells, it produces toxic effects

Question 205

Describe the transport & distribution of carotenoids.

Answer 205

• In the liver:
  
  • A small portion → retinol
  • A portion is incorporated into lipoproteins → extrahepatic tissues
• Transport and tissue uptake through lipoproteins

Question 206

Describe the role of retinoids in vision.

Answer 206

1. Light hits retina
2. Rhodopsin molecule is cleaved
3. Signals are sent to the brain (eyesight)
4. Rhodopsin: Opsin + vitamin A (retinal)
5. Vitamin A is needed to make more rhodopsin

Question 207

Vitamin A does not have a UL

True or False?

Answer 207

False.

• Once hepatic storage capacity for retinol is exceeded, toxicity may occur:
  
  • Acute → GI effect (e.g., nausea), headache
  • Chronic → liver abnormalities; reduced bone mineral density; bone and joint pain
  • Teratogenic → miscarriage; birth defects; permanent learning disabilities
• UL = 3000ug preformed vitamin A

Question 208

Vitamin A has a UL.

True or False?

Answer 208

True.

• Once hepatic storage capacity for retinol is exceeded, toxicity may occur:
  
  • Acute → GI effect (e.g., nausea), headache
  • Chronic → liver abnormalities; reduced bone mineral density; bone and joint pain
  • Teratogenic → miscarriage; birth defects; permanent learning disabilities
• UL = 3000ug preformed vitamin A

Question 209

Answer 209

Answer → A

High intakes can cause orange skin.

Question 210

What is selenium? List the different forms.

Answer 210

Selenium is an essential micronutrient, or trace element.

• (1) Inorganic forms (supplements and some plants)
  
  • selenide: Se^2- (H₂Se or Na₂Se)
  • selenite: Se⁴⁺ (H₂SeO₃ or Na₂SeO₃)
  • selenate: Se⁶⁺ (H₂SeO₄ or Na₂SeO₄)
• (2) Organic forms (selenoamino acids)
  
  • selenomethionine (mainly plants)
  • selenocysteine (mainly animals)

Question 211

Describe the metabolic functions of selenium. [3]

Answer 211

• Essential role in several important metabolic pathways, through selenoproteins (>25) with selenocysteine at the active site
  
  • (1) Glutathione (GSH) peroxidase → antioxidant enzyme which neutralizes hydrogen peroxide and other peroxides
  • (2) Thyroid hormone metabolism → iodothyronin 5’-diodinase (ID); important in converting different forms of thyroid hormone; inactive thyroxine (T₄) to active form thyronine (T₃)
  • (3) Antioxidant → selenoprotein P → antioxidant function: major selenium-containing protein in blood for selenium transport

Question 212

Describe the effects of selenium deficiency. [5]

Answer 212

• (1) Poor growth
• (2) Muscle pain and weakness → selenoprotein-N
• (3) Whitening of nail beds
• (4) Keshan’s Disease
  
  • Cardiomyopathy due to coxsackie virus
  • Low selenium increases susceptibility
• (5) Kashin-Beck’s disease
  
  • Osteoarthropathy = degeneration and necrosis of the joints and epiphyseal-plate cartilage
  • Low selenium plays a role (with other factors)

Question 213

List food sources and forms of selenium in the diet.

Answer 213

• Brazil nuts, seafood, meats, whole grains → soil selenium concentrations vary greatly; therefore, selenium content in food varies
• Forms in food and supplements:
  • Mainly in organic form
    
    • Plants and supplements:
      
      • Seleno_methionine_
      • Inorganic forms
    • Animal products:
      
      • Seleno_cysteine_

Question 214

Describe the interaction between selenium and potentially toxic metals.

Answer 214

• Selenium may help prevent some toxic effects associated with some metals, e.g., arsenic-associated skin lesions

Question 215

Discuss the potential role of selenium in disease prevention.

Answer 215

• Possible role in disease prevention due to its antioxidant function
  
  • Some epidemiological evidence to suggest a beneficial effect → suggested to reduce the risk of cancer and cardiovascular disease, but overall limited evidence.
  • In contrast, higher selenium concentrations in some studies associated with increased risk for diabetes, hypertension, and some cancers
  • Excess intake of selenium has adverse effects; small range between deficiency and excess.

Question 216

Explain why a tolerable upper intake level was derived for selenium.

Answer 216

• UL for selenium = 400ug/day for adults
• No regulation on selenium absorption
• High intakes = high uptakes; therefore, toxicity possible

Question 217

What are the possible effects of high intakes of selenium? [5]

Answer 217

• Chronic toxicity/chronic selenosis:
  
  • Hair and nail brittleness and loss = critical endpoint on which to base a UL
  • GI disturbances
  • Skin rash
  • Garlic breath odour due to excretion in breath
  • Nervous system abnormalities
• More likely from supplements than food forms of selenium.

Question 218

What is the suggested role of oxidative stress in chronic diseases? [5]

Answer 218

• Atherosclerosis
• Cancer
• Eye disease
• Autoimmune diseases
• Lung damage

Question 219

Answer 219

Answer → C

Most of what we eat are organic forms of selenium (selenocysteine and selenomethionine) are absorbed by amino acid transporters.

Less commonly consumed forms: Selenate via active diffusion and selinite via passive diffusion

Question 220

How was the RDA for selenium derived?

Answer 220

Based on depletion-repletion studies and on studies estimating obligatory losses of selenium over a range of intake allowed

Note: A single brazil nut provides more than the RDA.

Question 221

Answer 221

Answer → C

No right answer, some studies are leaning towards B, and some evidence suggests C.

Question 222

Answer 222

Answer → D

Question 223

Answer 223

Answer → B

Question 224

What does science say about antioxidant supplements & disease?

Answer 224

• Observational studies (cannot prove causal relationships) → higher consumption vegetables and fruits: lower risks of several diseases, including CVD, stroke, cancer, and cataracts
• Animal models → antioxidants interacted with free radicals and stabilized them, thus preventing the free radicals from causing cell damage → can these results be translated to human metabolism?
• 9 RCTs of dietary antioxidant supplements for cancer prevention worldwide → no evidence they are beneficial
• 1 systematic review → available evidence regarding use of vitamin and mineral supplements for chronic disease prevention

Question 225

Why don’t antioxidant supplements work? [4]

Answer 225

• Other factors in food
• Different dosage compared to foods
• Differences in the chemical composition of antioxidants in foods vs supplements
  
  • 8 forms of vitamin E in food but only alpha-tocopherol used in most studies
• Duration of antioxidant supplement use → not long enough to prevent chronic diseases

Question 226

What are three take-home messages about antioxidant supplements?

Answer 226

• Evidence for a benefit of antioxidant supplements in limited and mixed.
• In general, it seems better to get antioxidants through a healthy diet than through supplements.
• If you are considering a dietary supplement, first get information on it from reliable sources. High dose supplements (especially single nutrient supplements) may increase risk for some diseases and may interact with medications or other supplements.

Question 227

Describe the importance of bones. [4]

Answer 227

• ‘Internal framework’ of body
• Enable movement
• Protects the brain, heart, and other internal organs
• Mineral storage (e.g., calcium and phosphorus)

Question 228

Describe bone growth and modelling.

Answer 228

• Bone growth → occurs during stages of growth
  
  • Fetal development and infancy
  • Childhood
  • Adolescence
• Bone modelling → forms shape of bones; bone is dynamic tissue

Question 229

Describe bone remodelling. [3]

Answer 229

• Bone resorption and rebuilding → occurs throughout life
• Osteoclasts → bone resorbing cells → dissolve bone
• Osteoblasts → bone building cells → build new bone

Question 230

Describe peak bone mass.

Answer 230

• Childhood/adolescence → net bone growth
• Early to middle years of adulthood → no net change
• 35-40 years or older → net bone loss
• Note: Women lose bone mass faster than men due to menopause which reduces estrogen

Question 231

Describe osteoporosis, its risk factors both non-modifiable [3] and modifiable [4].

Answer 231

• Osteoporosis → reduced total bone mass (density); ‘porous’
• Risk factors
  
  • Non-modifiable
    
    • Estrogen deficiency → menopause reduces estrogen significantly
    • Ethnicity
    • Family history
  • Modifiable
    
    • Deficiency of vitamin D, calcium, phosphorus, magnesium
    • Physical inactivity
    • Excess alcohol
    • Smoking

Question 232

Describe osteomalacia, its risk factors [3], and the mechanism for development.

Answer 232

• Osteomalacia → inadequate mineralization of bone (i.e., soft bones) → in children = rickets
• Risk factors:
  
  • Inadequate dietary calcium intake
  • Insufficient calcium absorption due to vitamin D deficiency
  • Phosphate deficiency caused by increased renal losses
• Mechanism = Vitamin D deficiency
  
  • Decreased calcium absorption and decreased serum calcium
  • Decreased calcium for bone mineralization
  • Decreased phosphorus absorption
    
    • As bone turnover occurs, the bone matrix is preserved while bone mineralization is impaired

Question 233

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

Answer 233

• Vitamin D = calciferol; a.k.a. the sunshine vitamin
• Two main forms:
  
  • Ergocalciferol, D₂ → synthesized in plants
  • Cholecalciferol, D₃ → synthesized in animals
    
    • Differ only in side chains
    • Both can be converted to the active form and have the same metabolic activity
• Active form = 1,25-(OH)₂-D (calcitriol)

Question 234

List dietary sources of vitamin D.

Answer 234

• Food sources → fatty fish, liver, shitake mushrooms, fortified products (milk, orange juice)
• Forms in food → D₃ (animals); D₂ (plants)
• Forms in supplements/fortified foods → both

Question 235

Describe the pathways of digestion for vitamin D.

Answer 235

No digestion required

Question 236

Describe the pathways for absorption of vitamin D.

Answer 236

• Where → mostly jejunum
• How:
  
  • Absorbed in micelles by passive diffusion
  • Incorporated into chylomicrons in enterocyte
  • Chylomicrons → lymph → blood → liver → vitamin D to extrahepatic tissues
  • Chylomicron remnants → remaining vitamin D to the liver

Question 237

Describe the pathways of transport of vitamin D.

Answer 237

• Calcidiol (25(OH)D) = main circulating form in blood
  
  • Tightly bound to vitamin D binding protein
  • Half life = 2-3 weeks
  • Biomarker for vitamin D status assessment
  • Target: uptake by tissues (mainly kidney) for conversion to active hormone form, calcitriol
• Calcitriol (25(OH)₂D)
  
  • Loosely bound to vitamin D binding protein (facilitates tissue uptake)
  • Shorter half-life than calcidiol = 2-6 hours only
  • Acts in target tissues:
    
    • Bone, intestine, kidney
    • Also, heart, muscle, pancreas, and central nervous system

Question 238

What are the metabolites of vitamin D?

Answer 238

• Other metabolites of vitamin D

Question 239

Describe the pathways of excretion of vitamin D.

Answer 239

• Calcitroic acid is the major excretory product
• Conjugation and excretion via the bile

Question 240

Describe the pathway for endogenous synthesis of vitamin D.

Answer 240

• Vitamin D₃ (cholecalciferol) synthesized from 7-dehydrocholesterol in skin upon exposure to UVB

Question 241

What factors influence endogenous vitamin D synthesis?

Answer 241

• Lumisterol and tachysterol → lost as skin cells are sloughed → prevents over production → cannot get toxic levels from sun exposure!
• Endogenous synthesis is dependent on:
  
  • Sunblocks and sunscreen use
  • Skin pigment (lower synthesis with darker skin)
  • Aging (vitamin D synthesis decreases with age)
  • Time of day
  • Season & latitude → angle of the sun in the winter months in Canada is such that you cannot synthesize enough even with sun exposure.

Question 242

Explain the pathway and regulation of vitamin D activation.

Answer 242

• Liver (25-hydroxlyase): Vitamin D → 25(OH)D (calcidiol)
  
  • Most vitamin D in liver → converted to calcidiol and secreted into blood
• Calcidiol transport
  
  • Calcidiol = major circulating form in blood
  • Tightly bound to vitamin D binding protein (DBP)
  • Half life = 2-3 weeks
  • Biomarker for vitamin D status assessment
  • Target = uptake by tissues (mainly kidney) for conversion to the active hormone form of vitamin D, 1,25(OH)₂D (mainly in kidney)
• Kidney (1α-hydroxylase): Calcidiol → 1,25(OH)₂D (calcitriol)
  
  • Regulated process → stimulated by parathyroid hormone (PTH) → occurs with low calcium levels
• Transport of calcitriol
  
  • Loosely bound to DBP (facilitates tissue uptake)
  • Shorter half-life than calcidiol → 2-6 hours only
  • Acts on target tissues
    
    • Bone, intestine, kidney
    • Also, heart, muscle, pancreas, central nervous system.

Question 243

Describe how vitamin D is assessed.

Answer 243

Most commonly used indicator = serum 25(OH)D (calcidiol) concentration → strong correlation with dietary vitamin D intake

Question 244

Briefly list the metabolic functions of vitamin D. [2]

Answer 244

1. Genomic action → regulation of gene expression (>200 genes)
2. Non-genomic action → activation of signal transduction pathways; physiological responses

Question 245

Discuss risk factors and at risk populations for developing a vitamin D deficiency.

Answer 245

• Insufficient exposure to sunlight with inadequate dietary intake
  
  • Limited time outside, use of sun protection (clothing, sunscreen), higher latitudes
• Fat malabsorption and inadequate endogenous synthesis
• At risk populations:
  
  • Older adults → typically have lower intake and lower synthesis
  • Breastfed infants → human milk is low in vitamin D, infants most protected from sun exposure

Question 246

Discuss physiological implications of a vitamin D deficiency.

Answer 246

• Rickets in infants and children
  
  • A disorder of failed bone mineralization
  • Defective mineralization of cartilage and the epiphyseal growth plate
  • Bowing of legs with weight-bearing
• Osteomalacia in adults
  
  • Impaired bone remineralization = ‘softening’ of bones
  • Prolonged elevation of blood PTH

Question 247

Describe the symptoms of vitamin D toxicity. [3]

Answer 247

• Hypercalcemia; hyperphosphatemia
• Calcification of soft tissues
• Impaired renal function

Question 248

Comment on whether vitamin D intakes and recommendations may be too low.

Answer 248

• Depending on criteria used, up to 75% of people may have suboptimal vitamin D status
• Current recommendation is 15 mcg (600IU)
• Endocrine society suggests that 50mcg (2000IU) per day may be needed to raise low levels
• Bottom line → when possible, aim to get ~15 mins of sun exposure 2-3x per week for vitamin D synthesis
  
  • When this is not possible (winter months), take a supplement with 15-50mcg (600-2000IU)

Question 249

Describe vitamin D units.

Answer 249

• 0.025 mcg = 1 IU
• 15 mcg = 600 IU
• 25 mcg = 1000 IU

Question 250

Vitamin D has an AI.

True or False?

Answer 250

False.

Vitamin D has an RDA.

Question 251

Vitamin D has an RDA.

True or False?

Answer 251

True.

For me = 15 mcg/day = 600 IU

Question 252

Answer 252

Answer → D

Fat soluble vitamins → A, D, E, and K; absorption enhanced by dietary fats

Question 253

Describe the time required for synthesis of ~1000IU of vitamin D with exposure of face, neck, and arms, both for fair skin and darker skin.

Answer 253

• Notice from the graphs that darker skin requires longer exposure for the same amount of synthesis → trade-off → those with darker skin also have less DNA damage from UVB exposure because melanin is protective
• For European white skin → estimated that ~15 minutes of sun exposure is needed on arms and legs during peak sun hours 2-3 times per week (Hollick, 2014).

Question 254

Answer 254

Answer → D

Everyone in Canada requires a Vitamin D supplement in the winter months.

Question 255

What are the target tissues of the active hormone form of vitamin D? [7]

Answer 255

• Bone
• Intestine
• Kidney
• Heart
• Muscle
• Pancreas
• Central Nervous System

Question 256

Answer 256

Answer → B

Question 257

Describe the genomic action of vitamin D.

Answer 257

• Regulation of >200 genes
• Vitamin D binds to vitamin D receptor (VDR)
  
  • VDR/RXR complex
  • Vitamin D response element
  • Enhanced gene expression
• Increased expression of proteins needed to maintain calcium homeostasis
• Promotes differentiation of white blood cells, intestinal epithelial cells and osteoclasts
• Promotes proliferation of fibroblasts and keratinocytes

Question 258

Describe the non-genomic action of vitamin D.

Answer 258

• Via binding to vitamin D receptor on cell membranes
  
  • Activation of signal transduction pathways
  • Physiological responses
• May be important for:
  
  • Calcium absorption
  • Regulation of calcium channels in muscle

Question 259

Explain how vitamin D is involved in regulation of calcium status.

Answer 259

• Via genomic and non-genomic action → increases blood Ca
  
  • Low blood calcium → stimulates PTH release
  • PTH stimulates 1,25(OH)₂D synthesis in kidney
  • Increased 1,25(OH)₂D and PTH leads to [3]:
    
    • Increased calcium reabsorption in kidney
    • Increased intestinal absorption of calcium and phosphorus
    • Increased resorption of calcium and phosphorus from bone
      
      • Net result = Increased blood calcium

Question 260

Describe nutrient-nutrient interactions for vitamin D.

Answer 260

1. Calcium and phosphorus → uptake and serum levels regulated by vitamin D
2. Dietary lipids (fatty acids) → improve absorption of vitamin D

Question 261

Answer 261

Answer → C

Question 262

What is the mechanism for osteomalacia in adults?

Answer 262

• Vitamin D deficiency
  
  • Decreased calcium absorption and decreased serum calcium
  • Decreased calcium for bone mineralization
  • Decreased phosphorus absorption
    
    • As bone turnover occurs, the bone matrix is preserved while bone mineralization is impaired

Question 263

Vitamin D does not have a UL.

True or False?

Answer 263

False.

UL = 4000 IU for adults

• Symptoms of excess:
  
  • Hypercalcemia
  • Calcification of soft tissues
  • Impaired renal function

Question 264

Vitamin D has a UL.

True or False?

Answer 264

True.

UL = 4000 IU

• Symptoms of excess:
  
  • Hypercalcemia
  • Calcification of soft tissues
  • Impaired renal function

Question 265

Answer 265

Answer → E

Vegans → many sources are non-vegan

Older adult females → lower synthesis and lower intakes

This could be extended to everyone in winter months in higher latitudes.

Question 266

List some good dietary sources of calcium.

Answer 266

Natural food sources → dairy products; some seafood (e.g., salmon); nuts; legumes and legume products (especially tofu); some vegetables

Form of calcium in foods → insoluble calcium salts

Form of calcium in supplements → calcium carbonate, calcium citrate, and other salts (note; calcium carbonate requires acidity for digestion/absorption, so it is advised to take with food since food stimulates HCl production; this is not the case for calcium citrate)

Question 267

Describe how calcium is digested.

Answer 267

• Conversion of insoluble calcium salts to free Ca²⁺ (in the acidic stomach environment of the stomach via HCl)

Question 268

Describe how calcium is absorbed.

Answer 268

• Saturable, carrier-mediated, active transport
  
  • Carrier = TRPV6 (a.k.a. calcium transporter 1, CaT1)
  • Upregulated by calcitriol; decreases with age
  • Occurs in duodenum and proximal jejunum
• Paracellular diffusion → passive, nonsaturable, nonregulated process
  
  • Dose dependent
  • Occurs in jejunum and ileum

Question 269

Describe how and why absorption rate of calcium varies across the lifespan.

Answer 269

• Absorption rate is highest in infants and young children (60%)
• Absorption rate is lowest in older adults and women with low estrogen (15-20%); because [3]:
  
  • Calcium transporter expression decreases with age
  • Endogenous synthesis of vitamin D (required for calcium homeostasis/absorption)
  • Decreased stomach acidity (required for calcium digestion/absorption)

Question 270

Serum calcium concentration is under tight homeostatic regulation.

Which hormones regulate serum calcium concentration? [3]

Answer 270

• Hormones that regulate serum calcium concentration include:
  
  • PTH
  • Calcitriol
  • Calcitonin

Question 271

Describe the metabolic functions of calcium. [6]

Answer 271

1. Bone mineralization
2. Activator of muscle contraction
3. Cofactor in blood clotting → calcium needed for blood clotting factors
4. Signal transduction (Secondary messenger Ca²⁺)
5. Stimulation of enzyme activity (calmodulin)
6. Nerve transmission

Question 272

Discuss the nutrient-nutrient interactions for calcium.

Answer 272

• Absorption enhancers
  
  • Vitamin D
  • Sugars and sugar alcohols
  • Protein
• Absorption inhibitors
  
  • Fibre
  • Phytic acid
  • Oxaclic acid
  • Excessive divalent cations (Zn and Mg)
  • Unabsorbed fatty acids
• Urinary excretion enhancers:
  
  • Sodium
  • Protein
  • Caffeine
• Calcium impairs phosphorus, iron and fatty acids.

Question 273

Discuss the absorption enhancers [3] & inhibitors [6] for calcium, as well as urinary excretion enhancers [3]. Also note what calcium impairs. [3]

Answer 273

• Absorption enhancers
  
  • Vitamin D
  • Sugars and sugar alcohols
  • Protein
• Absorption inhibitors
  
  • Fibre
  • Phytic acid
  • Oxaclic acid
  • Excessive divalent cations (Zn²⁺ and Mg²⁺)
  • Unabsorbed fatty acids
• Urinary excretion enhancers:
  
  • Sodium
  • Protein
  • Caffeine
• Calcium impairs phosphorus, iron and fatty acids.

Question 274

Discuss risk factors [6] for developing calcium deficiency, and populations at risk [2].

Answer 274

• Alcohol use
• Corticosteroid use
• Calcium low
• Estrogen low
• Smoking
• Sedentary lifestyle
  
  • Populations at risk → adolescents and older adults in Canada due to low dietary intake; vitamin D inadequacy

Question 275

Explain the physiological implications of calcium deficiency. [3]

Answer 275

• Osteoporosis → reduced total bone mass (density)
• Neuromuscular impairment
  
  • Increase neuromuscular excitability
  • Intermittent contractions of muscle that fail to relax
  • Hand and feet muscles most affected
• Tetany
  
  • Characterized by continuous severe muscle spasms
  • Can cause respiratory dysfunction and death

Question 276

Describe the potential effects and causes [2] of excess calcium intake.

Answer 276

• Hypercalcemia → lethargy; anorexia; nausea; vomiting; heart arrhythmias; higher risk for kidney stones
• Causes
  
  • Usually from high dose supplements (or antacids)
  • Hyperparathyroidsm

Question 277

Describe the DRI for calcium.

Answer 277

RDA → established based on the amount required for bone health and to maintain adequate retention

Question 278

Answer 278

Answer → C

100g of spinach contains ~135mg calcium

Question 279

Answer 279

Answer → A

125mg x 32% = 40mg (milk)

50mg x 61% = 30mg (broccoli)

115mg x 5.1% = 7mg (spinach)

Question 280

Describe transport of calcium in enterocyte.

Answer 280

• Binding to calbindin
  
  • Shuttle across the cytosol
  • Release near basolateral membrane

Question 281

Describe transport of calcium across the basolateral membrane.

Answer 281

Ca²⁺-ATPase pump

Question 282

Describe calcium transport in hepatic portal vein.

Answer 282

• Same as in circulating blood
  
  • (1) Bound to protein, mainly albumin (40-45%)
  • (2) Complexed with sulfate, phosphate, citrate, and/or bicarbonate (up to 10%)
  • (3) Free Ca²⁺ (45-50%)

Question 283

Describe excretion of calcium.

Answer 283

• Excreted through urine and feces
• Fecal excretion = what was not absorbed
• Urinary excretion is regulated; 98% is reabsorbed

Question 284

Describe factors promoting urinary Ca excretion. [3]

Answer 284

• Protein → however; overall small effect on Ca balance because while high protein increases Ca excretion in the urine, high protein intake also increases calcium intestinal absorption (= no net effect)
• Caffeine → small losses (2-3mg Ca/cup of coffee)
• Na⁺ → share common reabsorption mechanism; higher Na⁺ intake = increased Calcium excretion

Question 285

Answer 285

Answer → C

Question 286

Answer 286

Answer → A

Hormones which increase serum calcium:

PTH

1,25-(OH)₂-D

Note: Calcidiol is the inactive form of vitamin D in the blood.

Question 287

Answer 287

Answer → C

Intestine → increases absorption

Bone → promotes resorption (i.e., release of calcium from bone)

Kidney → reabsorb more to keep it in the blood

Thyroid gland → vitamin D does not target this endocrine organ

Question 288

Describe the regulation and homeostasis of calcium at low calcium concentration.

Answer 288

• (1) PTH released by parathyroid gland in response to low circulating calcium levels
• (2) In kidney
  
  • PTH stimulates activation of calcidiol to calcitriol
  • PTH and calcitriol increase renal reabsorption of filtered calcium
• (3) In small intestine
  
  • Calcitriol enhances intestinal calcium absorption through increased transcription of (1) calbindin, (2) TRPV6, and (3) Ca²⁺-ATPase pumps
• (4) In bone
  
  • PTH and calcitriol stimulate osteoclasts which promote release of calcium from bone into blood
• (5) Once serum calcium levels are adequate, secretion and actions of PTH and calcitriol are suppressed

Question 289

Describe the regulate and homeostasis of calcium at high calcium concentration.

Answer 289

• High [Ca] stimulates release of calcitonin from the thyroid
  
  • Suppresses PTH production and release
  • Inhibits osteoclast activity → blocks calcium and phosphate release from bone
  • Promotes bone mineralization
  • Inhibits renal reabsorption of calcium and phosphate → enhanced urinary losses of calcium and phosphate
  • Eventually brings serum Ca back to the normal range

Question 290

Describe intracellular calcium concentration homeostatic regulation.

Answer 290

• To increase intracellular Ca²⁺ → activation of cell membrane channels allowing its entry; Ca²⁺ released from organelles
• To lower intracellular Ca²⁺ → release from cells via ATPase pumps; sequestered in organelles

Question 291

Answer 291

Answer → B

Tightly controlled mechanisms exist to keep serum and cellular calcium levels within a very narrow range, (at the expensive of bone calcium).

Question 292

Describe biomarkers for calcium.

Answer 292

• Lack of satisfactory test to measure calcium status on a routine basis.
• (1) Serum/plasma calcium (not effective due to tightly controlled regulation mechanisms)
  
  • So tightly regulated that it doesn’t reflect dietary intake or biochemical status
  • Measurement of disturbances in calcium metabolism
• (2) Non-invasive techniques to assess bone mineral density (more reliable methods)
  
  • DEXA scan
  • CT scan

Question 293

Answer 293

Answer → D

Calcium is needed for blood clotting factors, which are vitamin K dependent GLA-proteins.

Calcium is needed for bone mineralization; one of the vitamin K dependent proteins is osteocalcin (a GLA-protein) which helps to bind calcium and bring it into bone → important for bone mineralization

Question 294

When is calcium intake important in life?

Answer 294

Across the lifespan → not just in older adults or high-risk periods for osteoporosis; because → higher peak bone mass = more bone to lose before developing osteoporosis

Question 295

Calcium does not have a UL.

True or False?

Answer 295

False.

Hypercalcemia → lethargy; anorexia; nausea; vomiting; heart arrhythmias; higher risk for kidney stones

Question 296

Calcium has a UL.

True or False?

Answer 296

True.

Hypercalcemia → lethargy; anorexia; nausea; vomiting; heart arrhythmias; higher risk for kidney stones

Question 297

Describe the potential effects of low (i.e., suboptimal) calcium status.

Answer 297

• Low calcium intake/status has been associated with an increased risk of
  
  • Hypertension
  • Colon cancer
  • Type 2 diabetes
  • Obesity
• Causal relationship not confirmed to date

Question 298

Answer 298

Answer → E

A → symptoms of excess; however Jane is not exceeding the UL

Question 299

List the forms of phosphorus relevant to nutrition.

Answer 299

• Second most abundant mineral in the body
  
  • 85% in bone and teeth
  • 1% in ECF
  • 14% associated with soft tissues
• Occurs in the body in form of inorganic phosphate (P_i) and organic phosphates (bound to protein, saccharides, or lipids (e.g., phospholipids))

Question 300

Describe the metabolic functions of phosphorus. [5]

Answer 300

1. Structural component of bone
2. Component of multiple biological molecules (DNA; RNA; ATP; phospholipids; coenzyme forms of vitamins)
3. Regulation of enzyme function (glycogen phosphorylase; glycogen synthase)
4. Acid-base balance
5. Oxygen delivery (RBCs)

Question 301

List dietary sources of phosphorus.

Answer 301

• Natural food sources → meat; poultry; fish; eggs; dairy; nuts; legumes; grains; widely distributed in foods; phosphates in additives and colas
• Forms in foods → mostly organic forms in meats (phospholipids; phosphorylated proteins and saccharides); inorganic phosphates
  
  • In grains → phytic acid = not bioavailable

Question 302

Describe the process of digestion of phosphorus.

Answer 302

• Hydrolysis of organic phosphate compounds by phosphatases
  
  • Phospholipase C
  • Alkaline phosphatase on brush border

Question 303

Describe the process of absorption of phosphorus.

Answer 303

• Where → throughout small intestine
• How → as free inorganic phosphate ion
  
  • (1) paracellular diffusion (main)
  • (2) Sodium-dependent, saturable, carrier-mediated, active transport; enhanced by 1,25-(OH)₂-D
• Efficiency varies (50-80%); higher for animal sources
• Absorption not affected by body P status
  
  • High intakes
    
    • High serum P levels
    • Increased urinary excretion

Question 304

Describe the process of excretion of phosphorus.

Answer 304

• Excretion through urine and feces
• Urinary excretion = primary means of excreting phosphate and maintaining phosphate homeostasis
  
  • Excreted as inorganic phosphate ion
  • Reabsorbed with low-normal intakes
  • High serum phosphate promotes urinary phosphate excretion
  • Regulated by PTH and FGF23 → both promote excretion by diminishing reabsorption

Question 305

List factors [2] that inhibit the bioavailability of phosphorus.

Answer 305

• Inhibitors
  
  • Magnesium → formation of non-bioavailable complex
  • Calcium containing antacids (Ca acetate or carbonate → bind phosphorus

Question 306

Explain how phosphorus homeostasis is maintained, and compare this with regulation of calcium levels.

Answer 306

• Serum phosphate concentration are regulated but not as tightly as calcium
• Hormones involved in P regulation:
  
  • (1) Fibroblast growth factor (FGF) 23
  • (2) PTH → released by parathyroid gland
  • (3) Calcitriol
    
    • (1) and (2) inhibit P reabsorption in kidneys

Question 307

Discuss the likelihood of phosphorus deficiency.

Answer 307

• Rare, only seen in cases of:
  
  • Severe malnutrition
  • Other conditions such as hyperparathyroidism

Question 308

Explain the physiological implications of phosphorus deficiency. [3]

Answer 308

• Impaired bone health: rickets; osteomalacia; bone pain
• Skeletal muscle weakness and cardiomyopathy

Question 309

Describe potential symptoms [2] and causes [3] of excess phosphorus.

How is excess phosphorus status diagnosed?

Answer 309

• Causes
  
  • Excessive intakes from food additives and colas
  • Renal disease → impaired excretion of phosphates
  • Vitamin D toxicity
• Diagnostics
  
  • high serum phosphate (hyperphosphatemia)
• Symptoms
  
  • Calcification of non-skeletal tissues
  • Increased risk for atherosclerosis and heart disease

Question 310

What vitamins require phosphate? [7]

Answer 310

• Thiamin diphosphate (TDP)
• Pyridoxal 5’-phosphate (PLP)
• Flavin mononucleotide (FMN)
• Flavin adenine dinucleotide (FAD)
• Nicotinamide adenine dinucleotide (NADH)
• Nicotinaminde adenine dinucleotide phosphate (NADPH)
• Coenzyme A (CoA)

Question 311

Answer 311

Answer → E

Question 312

Describe the DRI for phosphorus.

Answer 312

• RDA based on balance studies

Question 313

Answer 313

Answer → E

Phosphorus is widely distributed in food, so deficiency due to inadequate intake is unlikely.

Question 314

Answer 314

Answer → B

Question 315

Summarize the roles of FGF23, calcitriol, and PTH in relation to phosphorus.

Answer 315

Question 316

Answer 316

Answer → C

Question 317

Answer 317

Answer → D

Decreased renal function leads to impaired urinary excretion.

Question 318

Describe enhancers [3] and inhibitors [6] of calcium absorption.

Answer 318

• Enhancers [3]
  
  • Protein intake → improves solubility
  • Presence of lactose and sugar alcohols → improves solubility
  • Gastric acidity
• Inhibitors [6]
  
  • Oxalic acid (spinach, rhubarb, swiss chard) → binds calcium and forms insoluble complex
  • Phytic acid (whole-grain breads, seeds, legumes) → binds calcium and forms insoluble complex
  • Magnesium, zinc → compete with calcium for absorption
  • Fibre → binds calcium so that it is not absorbed
  • Unabsorbed fatty acids → bind calcium and form calcium soaps that are not absorbed; mostly a concern for those with fat malabsorption disorders (e.g., liver disease, pancreatic disorders, cystic fibrosis, etc.)

Question 319

Describe enhancers of calcium bioavailability. [4]

Answer 319

• Enhancers [3]
  
  • Protein intake → improves solubility
  • Presence of lactose and sugar alcohols → improves solubility
  • Gastric acidity
  • Vitamin D → enhances expression of calcium transporters

Question 320

Describe inhibitors of calcium bioavailability. [6]

Answer 320

• Inhibitors [6]
  
  • Oxalic acid (spinach, rhubarb, swiss chard) → binds calcium and forms insoluble complex
  • Phytic acid (whole-grain breads, seeds, legumes) → binds calcium and forms insoluble complex
  • Magnesium & zinc → compete with calcium for absorption
  • Fibre → binds calcium so that it is not absorbed
  • Unabsorbed fatty acids → bind calcium and form calcium soaps that are not absorbed; mostly a concern for those with fat malabsorption disorders (e.g., liver disease, pancreatic disorders, cystic fibrosis, etc.)

Question 321

Describe four metabolic functions of magnesium.

Answer 321

• Bone mineralization/ structural component
• Enzymatic reactions
• Ion channel regulation (K and Ca channels)
• Enhances insulin release and action
• And more!

Question 322

Explain the processes involved in the digestion of magnesium.

Answer 322

None required

Question 323

Explain the processes involved in the absorption of magnesium. [2]

Answer 323

• Where → small intestine
• How → in Mg²⁺ form
  
  • (1) Saturable, carrier-mediated, active transport via TRPM6 → inhibited by high cytosolic Mg concentration
  • (2) Paracellular diffusion (main mechanism at high intakes) → increases as Mg concentration in lumen increases

Question 324

Explain the processes involved in the transport of magnesium. [3]

Answer 324

• Transport in blood, including hepatic portal vein
  
  • (1) Free Mg2+ (50-55%) = physiologically active form
  • (2) Bound to protein, mainly albumin (20-30%)
  • (3) Complexed with sulfate, phosphate, and citrate (5-15%)

Question 325

Explain the processes involved in the excretion of magnesium.

Answer 325

Excretion mainly through kidney → excretion is regulated, 95-97% is reabsorbed.

Question 326

Explain enhancers [3] and inhibitors [4] of magnesium absorption.

Answer 326

• Enhancers → protein & carbohydrates; high doses of vitamin D (enhances paracellular uptake)
• Inhibitors
  
  • Phytic acid (whole-grain breads, seeds, legumes)
  • Fibre
  • Unabsorbed fatty acids (in case of fat malabsorption; form soaps with Mg)
  • Phosphorus (forming non-bioavailable complex Mg₃(PO₄)₂.

Question 327

Explain factors that influence the excretion of magnesium. [6]

Answer 327

• Excretion affected by
  
  • Plasma Mg concentration
  • PTH
• Factors promoting Mg urinary excretion:
  
  • Diuretic medications
  • Protein
  • Alcohol
  • Caffeine

Question 328

Discuss risk factors for developing magnesium deficiency.

Answer 328

• Low intakes → common
  
  • Low intake of whole plant foods

Question 329

Explain the physiological implications of magnesium deficiency. Discuss diagnostics.

Answer 329

• Non-specific symptoms → delayed diagnosis
  
  • Fatigue, lethargy, weakness, nausea, vomiting
• Diagnostics
  
  • Plasma/serum magnesium concentration
  • Routinely measured indicator, but not sensitive and cutoff is debated

Question 330

Explain physiological implications of suboptimal intake of magnesium.

Answer 330

• Possible increased risk of
  
  • Hypertension
  • Type 2 diabetes
• Possible role of Mg:
  
  • Sleep
  • Leg cramps
  • Migraines
  • Depression and anxiety

Question 331

Describe symptoms of excess magnesium.

Answer 331

• Excessive magnesium from food sources does not cause toxicity, due to efficient renal excretion.
• Excessive intake possible from high-dose supplements.
• Symptoms
  
  • Diarrhea
  • Nausea, vomiting
  • Muscle weakness, paralysis

Question 332

Describe magnesium’s role in bone.

Answer 332

→ 50-60% of total body Mg is in bone → together with calcium and phosphorus → forms bone crystal lattice

Question 333

Describe magnesium’s role in enzymatic reactions.

Answer 333

Structural cofactor to stabilize enzyme or allosteric activator

→ assists in stabilization of ATP and transfer of phosphate group

• Enzymatic roles including in glucose, fat, protein, and nucleic acid metabolism

Question 334

Describe magnesium’s role in ion channel flux.

Answer 334

K and Ca Channels

• Mg is a ‘natural calcium channel blocker’ and also activates calcium ATPase → decreased intracellular calcium
• Mg is needed for Na/K+ pump and maintaining K+ concentration in cells
• Relevant for (1) nerve conduction, (2) muscle contraction, and (3) heart rhythm.

Question 335

Answer 335

Answer → E

Question 336

Describe dietary sources of magnesium and its forms in food.

Answer 336

• Natural food sources → nuts, seeds, whole grains, legumes, green leafy vegetables, seafood, dairy
• Form in foods → Mg²⁺
• Forms in supplements → Mg-citrate, Mg-gluconate, Mg-lactate

Question 337

Describe the DRI for magnesium.

Answer 337

RDA → established based on magnesium balance studies.

320mg/day for me!

Question 338

Answer 338

Answer → D

Question 339

How is Magnesium transported across the basolateral membrane?

Answer 339

Via Na+-ATPase pump

Question 340

Compare regulation and homeostasis of Ca, P & Mg.

Answer 340

Homeostasis is regulated at intestinal absorption and urinary excretion.

• Vitamin D enhances intestinal absorption of all three minerals: its main function is to increase calcium transporters to enhance calcium absorption, but it can also increase paracellular absorption of Mg and P at high levels as well.
• Vitamin D and PTH stimulate bone resorption so all three minerals are released.
• Vitamin D enhances renal reabsorption of calcium and phosphate, but not magnesium.
• PTH enhances renal reabsorption of calcium and magnesium, but inhibits the renal reabsorption of phosphate (i.e., enhances urinary excretion).
  
  • Calcium and phosphate can form an insoluble, inactive complex (calcium phosphate), so excreting more phosphate in urine when PTH levels are high can help to prevent this.
• FGF23 is released from bones when phosphate levels are high and inhibits renal reabsorption of phosphate and inhibits activation of vitamin D → acts to decrease phosphate levels.
• Calcitonin is released when calcium levels are high. It inhibits bone resorption to decrease calcium levels.

Question 341

Answer 341

Answer → A

Vitamin D enhances the expression of calcium transporters; vitamin D is critical for calcium absorption.

High doses of vitamin D enhance paracellular uptake of magnesium.

Question 342

Describe magnesium homeostasis when serum Mg is low.

Answer 342

• PTH enhances renal reabsorption (decrease urinary excretion)
• PTH activates vitamin D; vitamin D enhances absorption of magnesium
• PTH acts with vitamin D to increase bone resorption (minerals are released from bone, including magnesium)
• Net effect = increased serum magnesium levels

Question 343

Describe homeostasis of Mg when serum Mg is high.

Answer 343

• Mg transporters are inhibited; less is absorbed
• Magnesium itself inhibits renal reabsorption (urinary excretion increased)
• Net effect = decrease serum magnesium

Question 344

Answer 344

Answer → A

• PTH enhances renal reabsorption (decrease urinary excretion)
• PTH activates vitamin D; vitamin D enhances absorption of magnesium
• PTH acts with vitamin D to increase bone resorption (minerals are released from bone, including magnesium)
• Net effect = increased serum magnesium levels

Question 345

What is the interaction between phosphorus and magnesium?

Answer 345

High Mg inhibits P absorption → with increasing Mg intake → decreasing P absorption due to formation of Mg₃(PO₄)₂

Question 346

What is the interaction between potassium and magnesium?

Answer 346

Low Mg²⁺ associated with low K⁺

Low [Mg²⁺] → increasing K⁺ efflux from cells and subsequent renal K⁺ excretion

Question 347

What is the interaction between Calcium and magnesium?

Answer 347

• (1) Low Mg associated with hypocalcemia → Mg²⁺ cofactor for 25-hydroxylase which activates vitamin D
• (2) Excess Mg interferes with calcium function
  
  • Mg²⁺ reduces Ca²⁺ flux across membranes and activates Ca2+-ATPase pumps → reduces intracellular [Ca²⁺].
  • Mg²⁺ competes with Ca²⁺ for binding sites on troponin C and myosin → alters muscle contraction

Question 348

Answer 348

Answer → A

• Low magnesium → low calcitriol because the active form of vitamin D requires two hydroxylation steps, one of which requires magnesium
• Low magnesium is associated with low calcium through vitamin D
• Low magnesium disrupts the sodium-potassium pump and lets potassium be excreted out

Question 349

Answer 349

Answer → C

Question 350

Answer 350

Answer → B

Question 351

Answer 351

Answer → B

Vitamin D increases serum phosphate by increasing absorption (lesser effect than compared to calcium); increases renal absorption (countered by PTH which decreases renal absorption); enhance resorption from bone.

Question 352

Answer 352

Answer → A

Question 353

Answer 353

Answer → C

PTH secreted when calcium levels are low → acts to increase absorption, mostly through vitamin D; renal reabsorption and bone resorption

Question 354

Answer 354

Answer → B

PTH does increase bone resorption; but inhibits renal reabsorption → no net effect on serum P

Question 355

Answer 355

Answer → A

Question 356

Describe the main function of iodine.

Answer 356

• Main function = formation of thyroid hormones
  
  • Triiodothryonine (T₃) → 3 iodide
  • Thyroxine (T₄) → 4 iodide
• Thyroid hormone production and secretion → regulated by thyroid-stimulating hormone (TSH, also called thyrotropin)
  
  • TSH will result in an enlarged thyroid gland if iodide is deficient.

Question 357

List examples of natural and fortified food sources of iodine.

Answer 357

• Food → mostly animal sources → seafood; seaweed; dairy; smaller amounts in meats, grains & legumes
• Iodide content in plant and animal foods varies by region because soil iodide content greatly varies → Canada has low levels of iodide in soil
• Salt fortification in Canada → added to all table salts

Question 358

Explain the rationale for fortification of salt with iodide.

Answer 358

• Pre 1920’s goiter (enlarged thyroid due to iodine deficiency) was common in Canada due to low consumption/availability of iodine rich food sources
• Iodine added to all table salts in Canada → ¼ tsp provides ~90μg iodide
• Kosher, pickling, and sea salt → contains natural iodine, but not as much as iodized table salt.

Question 359

Explain how iodine is digested.

Answer 359

None required for free, ionic forms (iodide I^-)

Question 360

Explain how iodine is absorbed.

Answer 360

Rapid absorption mostly in stomach

Question 361

Explain how iodine is transported in the body.

Answer 361

• Free iodide in blood
• Highest uptake by thyroid glands through active transport
• Thyroid gland synthesizes and secretes thyroid hormones → 70-80% of total body iodide in thyroid gland as thyroid hormones

Question 362

Discuss nutrient-nutrient interactions for iodine. [4]

Answer 362

• Selenium, iron & vitamin A deficiency can enhance the effect of iodine deficiency → needed for iodide uptake and synthesis of thyroid hormones
• Goitrogens (i.e., known to increase risk of goiter) → glucosinolates in cabbage, kale, cauliflower, Goitrin in cassava → impaired uptake of iodide into thyroid gland

Question 363

List the methods for assessing iodine status. [3]

Answer 363

• Urinary iodine concentration → main biomarker
  
  • Changes with diet
  • Indicator for mild/moderate/severe deficiency but also of excess iodine status
• Thyroid gland → indirect indicator
  
  • Physiologic indicator of gland health
  • Enlargement of the thyroid gland in case of deficiency
• Serum TSH concentration
  
  • Increased concentration of thyroid-stimulating hormone in blood = indicator for potential iodine deficiency

Question 364

Describe the risk factors and physiological implications of iodine deficiency.

Answer 364

• Risk factors → areas without iodide fortification, especially if farther away from the ocean
• Deficiency → Goiter (swelling of thyroid gland)
  
  • In pregnancy → congenital iodine deficiency = impaired physical and intellectual development; stillbirths and spontaneous abortions
  • Maternal iodine deficiency during pregnancy is associated with impaired cognitive development in offspring → the effect of iodine deficiency in the first half of pregnancy is irreversible.

Question 365

Explain how easily one may achieve an excess iodine status.

Answer 365

Most people are very tolerant to excess intake; excess status is not likely due to efficient urinary excretion.

Iodine does still have a UL.

Question 366

Describe the manifestations of iodine toxicity.

Answer 366

• Thyroiditis (inflammation of thyroid gland)
• Goiter
• Hypothyroidism or hyperthyroidism
• Thyroid papillary cancer
• UL for iodine = 1100ug/day

Question 367

Answer 367

Answer → B

Fatigue, weight-gain, and high TSH are associated with iodine deficiency.

Question 368

Describe DRI for iodide.

Answer 368

RDA defined by studies quantifying the thyroid iodine accumulation and turnover rates

Question 369

Answer 369

Answer → E

Question 370

Describe the digestion and absorption of thyroid hormones.

Answer 370

• Absorbed unchanged (i.e., T₃ and T₄)
• Allows thyroid hormone medication to be administered orally

Question 371

Describe excretion of iodine.

Answer 371

• Urinary excretion (80-90%)
  
  • Kidneys have no reabsorption or other mechanism to control urinary iodide excretion
  • Excess dietary iodine that was absorbed into the blood stream but not taken up by tissues or thyroid glands is directly excreted
  • Urinary excretion fluctuates with recent dietary intake

Question 372

Answer 372

Answer → A

• Kidneys have no reabsorption or other mechanism to control urinary iodide excretion
• Excess dietary iodine that was absorbed into the blood stream but not taken up by tissues or thyroid glands is directly excreted.
• Urinary excretion fluctuates with recent dietary intake.

Question 373

What is the general criteria for definition of essential minerals?

Answer 373

• Inadequacy results in reproducible structural and/or physiological abnormalities or speicific biochemical changes.
• Adequacy can prevent abnormalities; sometimes, supplementation can reverse abnormalities

Question 374

What do thyroid hormones do?

Answer 374

• Adipose tissue → enhances lipolysis
• Muscle → enhances contraction
• Bone → promotes anabolism (growth and development)
• Cardiovascular system → increases heart rate
• GI tract → stimulates nutrient digestion and absorption
• Metabolism → stimulates metabolic rate and cellular oxygen consumption in metabolically active tissues

Question 375

Does salt restriction = iodine deficiency?

Answer 375

The science is unclear.

Takeaway → depends on what else people are eating; how much they are restricting salt; where the live in relation to the ocean & iodine rich soil

If you are trying to reduce sodium → reduce highly processed foods; continue to use table salt

Question 376

Which micronutrients have toxicity risk?

Answer 376

Vitamins A, D, E, C, B6, B3, and choline.

Question 377

Regular use of vitamin C supplements may reduce the duration and severity of colds.

True or False?

Answer 377

True.

Question 378

Regular use of vitamin C supplements may reduce the incidence of cancer or CVD.

True or False?

Answer 378

False.

Question 379

Regular use of vitamin C supplements may reduce the incidence of colds in the pediatric population.

True or False?

Answer 379

False.

Question 380

Regular use of vitamin C supplements may inhibit iron absorption.

True or False?

Answer 380

False.

Question 381

Ascorbic acid is released from bound proteins during digestion and absorption.

True or False?

Answer 381

False.

Question 382

Ascorbic acid is absorbed via a sodium dependent transporter.

True or False?

Answer 382

True.

Question 383

When ascorbic acid intakes exceed absorption capacity, the excess is excreted in the urine.

True or False?

Answer 383

False.

Question 384

Dehydroascorbic acid is reduced to ascorbic acid prior to absorption.

True or False?

Answer 384

False.

Dehydroascorbic acid is absorbed via GLUT transporters and then reduced to ascorbic acid within the enterocyte via glutathione reductase.

Question 385

Symptoms of scurvy include copper deficiency due to impaired absorption.

True or False?

Answer 385

False.

Question 386

Symptoms of scurvy include fatigue due to decreased absorption of heme iron.

True or False?

Answer 386

False.

Fatigue in scurvy is due to decreased carnitine synthesis.

Question 387

Symptoms of scurvy include ruptured blood vessels due to impaired carnitine synthesis.

True or False?

Answer 387

False.

Ruptured blood vessels occur due to decreased collagen synthesis.

Question 388

Symptoms of scurvy include increased bruising due to decreased reduction of copper.

True or False?

Answer 388

False.

Bruising is due to decreased collagen synthesis.

Question 389

Symptoms of scurvy include impaired wound healing due to decreased synthesis of collagen.

True or False?

Answer 389

True.

Question 390

Zinc deficiency is associated with impaired ability to taste. Which one of its metabolic functions best explains this association?

Answer 390

Component of metalloenzymes (gustin)

Question 391

At high intakes that exceed the RDA but are lower than the UL, urinary excretion of zinc will be upregulated.

True or False?

Answer 391

False

Question 392

At high intakes that exceed the RDA but are lower than the UL, the relative proportion of zinc absorbed will increase.

True or False?

Answer 392

False. Zinc absorption decreases

Question 393

At high intakes that exceed the RDA but are lower than the UL, zinc excretion in bile will be increased.

True or False?

Answer 393

False.

Question 394

At high intakes that exceed the RDA but are lower than the UL, zinc will be secreted into the lumen of the gut for excretion.

True or False?

Answer 394

True.

Question 395

At high zinc intakes that exceed the RDA but are lower than the UL, copper deficiency is likely.

True or False?

Answer 395

False.

Question 396

What is the richest dietary source of copper?

Answer 396

Oysters

Question 397

Zinc absorption is increased in the presence of amino acids.

True or False?

Answer 397

True

Question 398

Zinc absorption is increased at high zinc status.

True or False?

Answer 398

False.

Question 399

Zinc absorption is increased at high pH.

True or False?

Answer 399

False.

Zinc absorption is increased at low pH (high acidity).

Question 400

Zinc absorption is increased in the presence of phytic acid.

True or False?

Answer 400

False.

Phytic acid inhibits absorption of zinc.

Question 401

There is a narrow range between adequate and toxic intakes of selenium.

True or False?

Answer 401

True.

Question 402

Selenium is required for synthesis of steroid hormones.

True or False?

Answer 402

False.

Question 403

Most people would benefit from a selenium supplement.

True or False?

Answer 403

False.

Question 404

Selenium is most commonly found in the body as selenide.

True or False?

Answer 404

False.

Question 405

Deficiency of ATP7B leads to excess dietary copper absorption.

True or False?

Answer 405

False.

Question 406

Deficiency of ATP7B leads to impaired dietary copper absorption.

True or False?

Answer 406

False.

Question 407

Deficiency of ATP7B leads to increased copper excretion.

True or False?

Answer 407

False.

Question 408

Deficiency of ATP7B leads to decreased hepatic secretion of ceruloplasmin.

True or False?

Answer 408

True.

Question 409

Which micronutrients are needed for activation of some hormones of digestion, including gastrin and cholecystokinin?

Answer 409

Copper and vitamin C

Question 410

Current evidence suggests that higher intakes of antioxidants from foods may be associated with decreased risk for some chronic diseases; however, research on antioxidant supplements has not always shown the same benefits.

Why is this? [4]

Answer 410

• The higher doses of antioxidants in supplements can have harmful effects (e.g., beta-carotene increases risk of lung-cancer in smokers)
• It is difficult to trace the origin of chronic diseases to a set time or cause
• The form of antioxidants in supplements may not be the same as the beneficial form in foods.
• Foods contain other components that may have beneficial effects on health.

Question 411

Digestion for retinol and carotenoids begins in the stomach with release of bound proteins.

True or False?

Answer 411

True.

Question 412

Digestion for retinol and carotenoids is improved with the intake of fat-soluble vitamins.

True or False?

Answer 412

False.

Question 413

Digestion for retinol and carotenoids begins in the small intestine with cleavage of bound fatty acids.

True or False?

Answer 413

False.

Question 414

Digestion for retinol and carotenoids is enhanced when vitamin A is consumed with pectin.

True or False?

Answer 414

False.

Question 415

The main form of vitamin A transported in systemic circulation is cartenoids in lipoproteins.

True or False?

Answer 415

False.

The main form is retinol bound to RBP and transthyretin.

Question 416

The main form of vitamin A transported in systemic circulation is carotenoids bound to albumin.

True or False?

Answer 416

False.

The main form is retinol bound to RBP and transthyretin.

Question 417

The main form of vitamin A transported in systemic circulation is retinol bound to retinol binding protein and transthyretin.

True or False?

Answer 417

True.

Question 418

The main form of vitamin A transported in systemic circulation is retinol bound to cellular retinol binding protein (CRBP).

True or False?

Answer 418

False.

The main form of vitamin A transported in systemic circulation is retinol bound to retinol binding protein and transthyretin.

Question 419

The main form of vitamin A transported in systemic circulation is retinol in lipoproteins.

True or False?

Answer 419

False.

The main form is retinol bound to RBP and transthyretin.

Question 420

How many stereoisomers of beta-tocopherol exist?

Answer 420

8

Question 421

A supplement contains 20mg of all-racemic alpha-tocopherol and 15 mg of R-alpha tocotrienol.

How many mg alpha tocopherol does the supplement provide?

Answer 421

10 mg

Question 422

Phosphorus improves calcium absorption.

True or False?

Answer 422

False.

Question 423

Lactose improves calcium absorption.

True or False?

Answer 423

True.

Question 424

Magnesium improves calcium absorption.

True or False?

Answer 424

False.

Question 425

Phytic acid improves calcium absorption.

True or False?

Answer 425

False.

Question 426

Unabsorbed fatty acids improve calcium absorption.

True or False?

Answer 426

False.

Question 427

High calcium concentrations are sensed primarily by the […], which then secretes […] to reduce plasma calcium.

Answer 427

High calcium concentrations are sensed primarily by the thyroid, which then secretes calcitonin to reduce plasma calcium.

Question 428

Your friend, Ali (24 years old) presents you with evidence to suggest that calcium supplements can increase the risk of heart disease. She is now concerned about the calcium supplements that her doctor recommended she take.

Which of the following would be the most appropriate reply to this?

Answer 428

There is a slightly increased risk of heart disease with calcium supplements, but if her health provider suggests she needs a supplement the benefits of taking it probably outweigh the risks.

Question 429

Paracellular absorption of calcium increases with low dietary calcium intakes.

True or False?

Answer 429

False.

Question 430

Paracellular calcium absorption requires energy and is saturable.

True or False?

Answer 430

False.

Question 431

Paracellular absorption of calcium requires a membrane channel protein (called TRPV6).

True or False?

Answer 431

False.

Question 432

Paracellular absorption of calcium occurs by diffusion mainly in the jejunum and ileum.

True or False?

Answer 432

True.

Question 433

Calcium intakes in Canada have increased over time due to an increased availability of alternative milks.

True or False?

Answer 433

False.

Question 434

Calcium intakes in Canada have decreased over time, mostly due to decreased milk intake.

True or False?

Answer 434

True.

Question 435

Calcium intakes in Canada are low in most people, except for older adults who appear to have mostly adequate intakes.

True or False?

Answer 435

False.

Question 436

Calcium intakes in Canada are generally quite high, with most people meeting the RDA for calcium.

True or False?

Answer 436

False.

Question 437

Kevin lives in Hawaii. He spends most of his time outdoors but always wears sunscreen (SPF 30). He takes a vitamin D supplement daily (1000 IU/25 mcg per day) and does not drink cow’s milk but consumes calcium and vitamin D fortified oat milk occasionally.

What would be the most appropriate advice for Kevin?

Answer 437

Take the supplement with a meal including fat to enhance absorption.

Question 438

Most phosphorus, regardless of its dietary form, is absorbed from the GI tract bound to lipids.

True or False?

Answer 438

False.

Most is absorbed as free inorganic phosphate ions.

Question 439

Most phosphorus, regardless of its dietary form, is absorbed from the GI tract bound to proteins.

True or False?

Answer 439

False.

Most is absorbed as free inorganic phosphate ions.

Question 440

Most phosphorus, regardless of its dietary form, is absorbed from the GI tract with calcium.

True or False?

Answer 440

False.

Most is absorbed as free inorganic phosphate ions.

Question 441

Most phosphorus, regardless of its dietary form, is absorbed from the GI tract through active transport.

True or False?

Answer 441

False.

Question 442

Most phosphorus, regardless of its dietary form, is absorbed from the GI tract as free inorganic phosphate ions.

True or False?

Answer 442

True.

Question 443

Milk is a good source of vitamin D because it is fortified with calcitriol.

True or False?

Answer 443

False.

It is fortified with cholecalciferol.

Question 444

Milk is a good source of vitamin D because it naturally provides cholecalciferol.

True or False?

Answer 444

False.

It is fortified with cholecalciferol.

Question 445

Milk is a good source of vitamin D because it naturally provides calcitriol.

True or False?

Answer 445

False.

It is fortified with cholecalciferol.

Question 446

Milk is a good source of vitamin D because it is fortified with calcidiol.

True or False?

Answer 446

False.

It is fortified with cholecalciferol.

Question 447

Milk is a good source of vitamin D because it is fortified with cholecalciferol.

True or False?

Answer 447

True

Question 448

Both calcitriol and FGF23 decrease serum phosphorus levels.

True or False?

Answer 448

False.

Question 449

Calcitriol and FGF23 have opposing effects on the levels of phosphorus in extracellular fluids.

True or False?

Answer 449

True.

Question 450

Calcitriol inhibits renal reabsorption of phosphorus, but FGF23 promotes renal reabsorption of phosphorus.

True or False?

Answer 450

False.

Question 451

Calcitriol stimulates the release of phosphorus from bone, but FGF23 inhibits the release of phosphorus from bone.

True or False?

Answer 451

False

Question 452

Both calcitriol & FGF23 increase phosphorus absorption.

True or False?

Answer 452

False.

Question 453

In addition to bone health, which micronutrient is also important for acid-base balance in the body?

Answer 453

Phosphorus

Question 454

Why are vitamin D requirements highest in older adults aged >70years?

Answer 454

There is a reduction in vitamin D formation in the skin with increasing age.

Question 455

What is the form of phosphate consumed in phospholipids in meat?

Answer 455

Organic phosphate

Question 456

How do ergocalciferol and cholecalciferol differ? [2]

Answer 456

• Chemical structure
• Dietary sources
• They have the same function

Question 457

Vitamin D status is assessed by measuring plasma calcidiol. This is partly because it has a very short half life in the plasma.

True or False?

Answer 457

False.

It reflects both endogenous synthesis and exogenous intake of vitamin D.

Question 458

Vitamin D status is assessed by measuring plasma calcidiol. This is partly because it is in equilibrium with tissue calcitriol.

True or False?

Answer 458

False.

It reflects both endogenous synthesis and exogenous intake of vitamin D.

Question 459

Vitamin D status is assessed by measuring plasma calcidiol. This is partly because it reflects both endogenous synthesis and exogenous intake of vitamin D.

True or False?

Answer 459

True.

Question 460

Vitamin D status is assessed by measuring plasma calcidiol. This is partly because its synthesis is highly regulated.

True or False?

Answer 460

False.

It reflects both endogenous synthesis and exogenous intake of vitamin D.

Question 461

Vitamin D status is assessed by measuring plasma calcidiol. This is partly because it is the functional form of vitamin D.

True or False?

Answer 461

False.

Calcitriol is the functional form.

Calcidiol (the main circulating form) reflects both endogenous synthesis and exogenous intake of vitamin D.

Question 462

Describe why PTH enhances renal reabsorption of calcium and magnesium, but inhibits the renal reabsorption of phosphate (i.e., enhances its urinary excretion).

Answer 462

PTH activates vitamin D which enhances intestinal absorption and bone resorption of Ca, P and Mg.

Calcium and phosphate can form an insoluble, inactive complex (calcium phosphate), so excreting more phosphate in urine when PTH levels are high can help to prevent this.

Question 463

Zinc is important for healthy glucose tolerance.

True or False?

Answer 463

True.

Insulin response and glucose tolerance → signalling and release; impaired glucose tolerance in zinc deficiency

Question 464

Copper is important for healthy glucose tolerance.

True or False?

Answer 464

False.

Insulin response and glucose tolerance → signalling and release; impaired glucose tolerance in zinc deficiency

Question 465

Describe neuromuscular impairment due to calcium deficiency. [3]

Answer 465

• Neuromuscular impairment
  
  • Increase neuromuscular excitability
    
    • Basically calcium prevents rapid depolarization caused by sodium entering the cell (down its electrochemical gradient). So less calcium, quicker depolarization.
  • Intermittent contractions of muscle that fail to relax
  • Hand and feet muscles most affected

Question 466

Describe tetany caused by calcium deficiency [2].

Answer 466

• Tetany
  
  • Characterized by continuous severe muscle spasms
  • Can cause respiratory dysfunction and death

Question 467

What inhibits TRPM6?

Answer 467

Saturable, carrier-mediated, active transport of Mg via TRPM6 → inhibited by high cytosolic Mg concentration

Question 468

Describe carnitine’s role in energy production.

Answer 468

• Carnitine transports long-chain fatty acids into the mitochondria so they can be oxidized (“burned”) to produce energy.
• It also transports the toxic compounds generated out of the mitochondria to prevent their accumulation.

Question 469

Too much sun exposure can lead to vitamin D toxicity.

True or False?

Answer 469

False.

• Lumisterol and tachysterol → lost as skin cells are sloughed → prevents over production → cannot get toxic levels from sun exposure!

Question 470

You cannot induce vitamin D toxicity from too much sun exposure.

True or False?

Answer 470

True.

• Lumisterol and tachysterol → lost as skin cells are sloughed → prevents over production → cannot get toxic levels from sun exposure!

Question 471

Excessive magnesium intake from food may cause toxicity.

True or False?

Answer 471

False.

• Excessive magnesium from food sources does not cause toxicity, due to efficient renal excretion.
• Excessive intake possible from high-dose supplements.
• Symptoms
  
  • Diarrhea
  • Nausea, vomiting
  • Muscle weakness, paralysis

Question 472

Excessive magnesium from food does not cause toxicity.

True or False?

Answer 472

True.

• Excessive magnesium from food sources does not cause toxicity, due to efficient renal excretion.
• Excessive intake possible from high-dose supplements.
• Symptoms
  
  • Diarrhea
  • Nausea, vomiting
  • Muscle weakness, paralysis

Question 473

Excessive magnesium from supplements is possible.

True or False?

Answer 473

True.

• Excessive magnesium from food sources does not cause toxicity, due to efficient renal excretion.
• Excessive intake possible from high-dose supplements.
• Symptoms
  
  • Diarrhea
  • Nausea, vomiting
  • Muscle weakness, paralysis

Question 474

Excessive magnesium from supplements is not possible.

True or False?

Answer 474

False.

• Excessive magnesium from food sources does not cause toxicity, due to efficient renal excretion.
• Excessive intake possible from high-dose supplements.
• Symptoms
  
  • Diarrhea
  • Nausea, vomiting
  • Muscle weakness, paralysis

Question 475

Phosphorus absorption is affected by high body P status.

True or False?

Answer 475

False.

• Absorption not affected by body P status
  
  • High intakes lead to:
    
    • High serum P levels
    • Increased urinary excretion

Question 476

Phosphorus absorption is not affected by high body P status.

True or False?

Answer 476

True.

• Absorption not affected by body P status
  
  • High intakes lead to:
    
    • High serum P levels
    • Increased urinary excretion

Question 477

Digestion of zinc requires release from proteins and nucleic acids.

True or False?

Answer 477

True.

Question 478

Digestion of zinc requires release from lipids.

True or False?

Answer 478

False.

Digestion of zinc requires release from proteins and nucleic acids.

Question 479

Digestion of zinc requires reduction of zinc to Zn²⁺.

True or False?

Answer 479

False.

Digestion of zinc requires release from proteins and nucleic acids.

Question 480

TrNo digestion is required for zinc.

True or False?

Answer 480

False.

Digestion of zinc requires release from proteins and nucleic acids.

Question 481

PTH is important for regulating serum calcium levels.

True or False?

Answer 481

True.

Question 482

25(OH)D is important for regulating serum calcium levels.

True or False?

Answer 482

False.

Question 483

Calmodulin is important for regulating serum calcium levels.

True or False?

Answer 483

False.

However, one of the metabolic functions of calcium is stimulation of enzyme activity, including calmodulin.

Question 484

Which form of vitamin A binds to opsin to form rhodopsin?

Answer 484

cis-Retinal

Question 485

Synthesis of melanin is a function of copper.

True or False?

Answer 485

True.

Tyrosinase → copper containing metalloenzyme which synthesizes melanin.

Question 486

Activation of hormones is a function of copper.

True or False?

Answer 486

True.

Some of these hormones include gastrin, cholecystokinin, vasopressin, and calcitonin.

Question 487

Cell differentiation is a function of copper.

True or False?

Answer 487

False.

Question 488

Copper has antioxidant function.

True or False?

Answer 488

True.

Cu/Zn superoxide dismutase.

Question 489

Copper is involved in the synthesis of collagen.

True or False?

Answer 489

True.

Question 490

alpha-tocopherol is the most active form of vitamin E because alpha-tocopherol transfer protein preferentially secretes vitamin E from the liver.

True or False?

Answer 490

True.

Question 491

alpha-tocopherol is the most active form of vitamin E because alpha-tocopherol transfer protein preferentially absorbs vitamin E from the liver.

True or False?

Answer 491

False.

alpha-tocopherol is the most active form of vitamin E because alpha-tocopherol transfer protein preferentially secretes vitamin E from the liver.

Question 492

alpha-tocopherol is the most active form of vitamin E because transfer proteins preferentially secrete other forms into bile (and thus feces).

True or False?

Answer 492

False.

alpha-tocopherol is the most active form of vitamin E because alpha-tocopherol transfer protein preferentially secretes vitamin E from the liver.

Question 493

alpha-tocopherol is the most active form of vitamin E because alpha-tocopherol is the only form with antioxidant actions.

True or False?

Answer 493

False.

alpha-tocopherol is the most active form of vitamin E because alpha-tocopherol transfer protein preferentially secretes vitamin E from the liver.

Question 494

alpha-tocopherol is the most active form of vitamin E because other forms are rapidly taken up by adipose tissue.

True or False?

Answer 494

False.

alpha-tocopherol is the most active form of vitamin E because alpha-tocopherol transfer protein preferentially secretes vitamin E from the liver.

Question 495

Menke’s disease leads to deficiency of copper due to decreased brush border absorption of copper through ATP7A.

True or False?

Answer 495

False.

Menke’s disease leads to deficiency of copper due to decreased release of copper from enterocytes through ATP7A.

Question 496

Menke’s disease leads to deficiency of copper due to decreased release of copper from enterocytes through ATP7A.

True or False?

Answer 496

True.

Question 497

Menke’s disease leads to deficiency of copper due to increased hepatic excretion of copper through ATP7A.

True or False?

Answer 497

False.

Menke’s disease leads to deficiency of copper due to decreased release of copper from enterocytes through ATP7A.

Question 498

Menke’s disease leads to deficiency of copper due to increased renal excretion of copper through ATP7B.

True or False?

Answer 498

False.

Menke’s disease leads to deficiency of copper due to decreased release of copper from enterocytes through ATP7A.

Question 499

Menke’s disease leads to deficiency of copper due to increased storage of copper in metallothionein.

True or False?

Answer 499

False.

Menke’s disease leads to deficiency of copper due to decreased release of copper from enterocytes through ATP7A.

Question 500

Magnesium and calcium have antagonistic function in muscle contraction, with calcium promoting the process and magnesium being the inhibitor if bound to sites that are normally occupied by calcium.

True or False?

Answer 500

True.

Question 501

Magnesium promotes phosphorus absorption.

True or False?

Answer 501

False.

Question 502

Calcium and magnesium promote each other’s reabsorption in the kidney.

True or False?

Answer 502

False.

Question 503

Calcium may cause an alteration in magnesium distribution by changing the flux of magnesium across the cell membrane or displacing it on its binding site.

True or False?

Answer 503

False.

Question 504

Vitamin C is needed to reduce copper to the active Cu⁺ form.

True or False?

Answer 504

True.

Question 505

Vitamin C is needed to reduce copper to the active Cu²⁺ form.

True or False?

Answer 505

False.

Vitamin C is needed to reduce copper to the active Cu⁺ form.

Question 506

Vitamin C is needed to oxidize copper to the active Cu⁺ form.

True or False?

Answer 506

False.

Vitamin C is needed to reduce copper to the active Cu⁺ form.

Question 507

Vitamin C is needed to oxidize copper to the active Cu²⁺ form.

True or False?

Answer 507

False.

Vitamin C is needed to reduce copper to the active Cu⁺ form.

Question 508

Copper absorption mainly occurs through carrier mediated absorption that is increased at high intakes of copper.

True or False?

Answer 508

False.

Copper absorption mainly occurs through carrier mediated absorption that is reduced at high intakes of copper.

Question 509

Copper absorption occurs mainly through carrier mediated absorption that is reduced at high intakes of copper.

True or False?

Answer 509

True.

Question 510

Copper absorption occurs mainly through carrier mediated absorption that is not influenced by intakes of copper.

True or False?

Answer 510

False.

Copper absorption mainly occurs through carrier mediated absorption that is reduced at high intakes of copper.

Question 511

Copper absorption mainly occurs through paracellular diffusion.

True or False?

Answer 511

False.

Paracellular diffusion occurs at high intakes. Copper absorption mainly occurs through carrier mediated absorption that is reduced at high intakes of copper.

Question 512

Copper absorption mainly occurs through passive transcellular diffusion.

True or False?

Answer 512

False.

Question 513

Phosphorus absorption primarily occurs through non-saturable passive paracellular diffusion.

True or False?

Answer 513

True.

Question 514

Phosphorus absorption primarily occurs through non-saturable active transport.

True or False?

Answer 514

False.

Phosphorus absorption primarily occurs through non-saturable passive paracellular diffusion.

Question 515

Phosphorus absorption primarily occurs through saturable carrier dependent transport.

True or False?

Answer 515

False.

Phosphorus absorption primarily occurs through non-saturable passive paracellular diffusion.

Question 516

Phosphorus absorption primarily occurs through saturable passive transcellular diffusion.

True or False?

Answer 516

False.

Phosphorus absorption primarily occurs through non-saturable passive paracellular diffusion.

Question 517

Zinc and iron compete for intestinal absorption through DMT1 transporter.

True or False?

Answer 517

True.

Question 518

In the presence of copper, more zinc is stored in metallothionein.

True or False?

Answer 518

False.

Question 519

Copper is excreted primarily through urine.

True or False?

Answer 519

False.

Copper is excreted primarily through feces.

Question 520

Copper is excreted primarily through feces.

True or False?

Answer 520

True.

Question 521

Copper is excreted primarily through sweat and skin.

True or False?

Answer 521

False.

Copper is excreted primarily through feces.

Question 522

What are the two disorders associated with selenium deficiency?

Answer 522

• Keshan → selenium deficiency increases susceptibility of cardiomyopathy due to coxsackie virus
• Kashin Beck → selenium deficiency plays a role; osteoarthropathy

Question 523

The main effect of copper toxicity is neurological deficits.

True or False?

Answer 523

False.

The main effect of copper toxicity is liver damage.

Question 524

The main effect of copper toxicity is zinc deficiency.

True or False?

Answer 524

False.

The main effect of copper toxicity is liver damage.

Question 525

The main effect of copper toxicity is iron deficiency.

True or False?

Answer 525

False.

The main effect of copper toxicity is liver damage.

Question 526

The main effect of copper toxicity is liver damage.

True or False?

Answer 526

True

Question 527

The main effect of copper toxicity is skin rash.

True or False?

Answer 527

False.

The main effect of copper toxicity is liver damage.

Question 528

Vitamin A deficiency can lead to anemia.

True or False?

Answer 528

False.

Question 529

Vitamin A deficiency can lead to cheilosis.

True or False?

Answer 529

False.

Question 530

Vitamin A deficiency can lead to xeropthalmia.

True or False?

Answer 530

True.

Question 531

Vitamin A deficiency can lead to impaired blood clotting.

True or False?

Answer 531

False.

Question 532

Animal products are a good source of retinoids and carotenoids.

True or False?

Answer 532

False, animal products are only a good source of retinoids.

Question 533

What form does phosphorus take in the diet?

Answer 533

Inorganic phosphates and organic phosphates (bound to DNA, proteins, etc.)

Question 534

Why is there a theoretical increased risk of kidney stones with high intakes of vitamin C?

Answer 534

Metabolism of vitamin C to oxalic acid for excretion in urine.

Question 535

Vitamin C absorption is down-regulated at high intakes.

True or False?

Answer 535

True.

Question 536

Vitamin C absorption is up-regulated at high intakes.

True or False?

Answer 536

False.

Vitamin C absorption is down-regulated at high intakes.

Question 537

Excess vitamin C is efficiently excreted in urine.

True or False?

Answer 537

True.

Question 538

What form of vitamin D is found in naturally occurring cod liver oil?

Answer 538

Cholecalciferol, D3

Question 539

What form of vitamin D is found in shitaake mushrooms?

Answer 539

Ergocalciferol, D2

Question 540

Why are carotenoids potent antioxidants?

Answer 540

Conjugated double bonds

Question 541

Is serum calcium a sensitive indicator of calcium status?

Answer 541

No, because serum calcium levels are tightly regulated.

Question 542

Calcium supplements should be taken at separate times from […] supplements because of potential interactions inhibiting absorption.

Answer 542

Calcium supplements should be taken at separate times from iron supplements because of potential interactions inhibiting absorption.

Question 543

Phosphorus deficiency is rare, but is more likely to occur among individuals […].

Answer 543

Phosphorus deficiency is rare, but is more likely to occur among individuals with hyperparathyroidism or severe malnutrition.

Question 544

Phosphorus toxicity is more likely to occur in individuals with renal failure.

True or False?

Answer 544

True.

Question 545

Phosphorus toxicity is more likely to occur in individuals with liver failure.

True or False?

Answer 545

False.

Phosphorus toxicity is more likely to occur in individuals with renal failure.

Question 546

Phosphorus toxicity is more likely to occur in individuals with high intakes of calcium.

True or False?

Answer 546

False.

Phosphorus toxicity is more likely to occur in individuals with renal failure.

Question 547

Phosphorus toxicity is more likely to occur in individuals with high intakes of antacids.

True or False?

Answer 547

False.

Phosphorus toxicity is more likely to occur in individuals with renal failure.

Question 548

Which mineral participates in all aspects of energy metabolism including glycolysis, beta-oxidation, and the TCA cycle?

Answer 548

Magnesium

Question 549

Wilson’s disease is associated with increased storage of copper in the liver.

True or False?

Answer 549

True.

Question 550

Wilson’s disease is associated with decreased excretion of copper in urine.

True or False?

Answer 550

False.

Wilson’s disease is associated with increased storage of copper in the liver.

Question 551

Wilson’s disease is associated with toxic levels of copper in the plasma.

True or False?

Answer 551

False.

Wilson’s disease is associated with increased storage of copper in the liver.

Question 552

Wilson’s disease is associated with decreased absorption of copper.

True or False?

Answer 552

False.

Wilson’s disease is associated with increased storage of copper in the liver.

Question 553

Wilson’s disease is associated with inhibition of copper function in RBCs.

True or False?

Answer 553

False.

Wilson’s disease is associated with increased storage of copper in the liver.

Question 554

How does a clinical magnesium deficiency (extreme case) lead to hypocalcemia?

Answer 554

Reduced activation of vitamin D

Question 555

Which bone nutrients are more likely to be of concern in vegan diets?

Answer 555

Calcium

Vitamin D

Question 556

Magnesium supplements may be beneficial for sleep disorders.

True or False?

Answer 556

True.

Question 557

Magnesium supplements may be beneficial for leg cramps.

True or False?

Answer 557

True.

Question 558

Magnesium supplements may be beneficial for preventing colds.

True or False?

Answer 558

False.

Question 559

Magnesium supplements may be beneficial for anxiety.

True or False?

Answer 559

True.

Question 560

How does iodine deficiency lead to goiter?

Answer 560

Low iodine stimulates release of TSH which increases thyroid growth.

Question 561

What does iodide deficiency during pregnancy lead to?

Answer 561

Irreversible impaired cognitive development in offspring.

Question 562

Your friend, Bob has been taking zinc supplements (50 mg/day), as he heard it will boost his immune system during the cold season. He has an otherwise healthy and balanced diet.

List three nutrients that may be affected by this high intake of zinc and briefly describe the interaction for each.

Answer 562

• Iron → high zinc may reduce iron absorption
• Calcium → high zinc may interfere with calcium absorption
• Copper → high zinc increases metallothionein which may ‘trap’ copper in the enterocyte and reduce its absorption

Question 563

Your friend, Bob has been taking zinc supplements (50 mg/day), as he heard it will boost his immune system during the cold season. He has an otherwise healthy and balanced diet.

List three physiological effects of chronic zinc toxicity.

Answer 563

• Suppression of immune system
• Copper deficiency
• Anemia

Question 564

Your friend, Bob has been taking zinc supplements (50 mg/day), as he heard it will boost his immune system during the cold season. He has an otherwise healthy and balanced diet.

Would you expect that taking zinc daily will reduce Bob’s risk of getting a cold? Explain.

Answer 564

No, current evidence suggests that taking a zinc supplement does not appear to reduce the risk of getting a cold.

Question 565

Your friend, Bob has been taking zinc supplements (50 mg/day), as he heard it will boost his immune system during the cold season. He has an otherwise healthy and balanced diet.

A friend mentions that he should take vitamin C in addition to taking zinc. What does current evidence suggest regarding the association between vitamin C supplements and the common cold?

Answer 565

Evidence suggests that taking vitamin C will not reduce the incidence of common colds, but may decrease the duration and severity of a cold.

Question 566

Describe one antioxidant function for each of: selenium, copper, zinc, vitamin E and vitamin C.

Answer 566

Selenium → cofactor for glutathione peroxidase

Copper → cofactor for Cu/Zn superoxide dismutase

Zinc → structural component of Cu/Zn superoxide dismutase

Vitamin E → termination of lipid peroxidation chain reaction

Vitamin C → reduction of alpha-tocopherol radical (oxidized vitamin E)

Question 567

Describe three ways the antioxidant nutrients interact.

Answer 567

1. Cu and Zn both required for Cu/Zn superoxide dismutase

2. Vit C needed for regeneration of oxidized vitamin E

3. Se and vitamin E both needed for prevention/reducing damage from lipid peroxidation → Vitamin E can donate an electron + hydrogen to an LOO• radical, forming LOOH, and glutathione peroxidase converts this lipid peroxide to a lipid alcohol (LOH). So vitamin E and glutathione peroxidase work together to eliminate free radicals that form in cell membrane lipids.

Question 568

What metabolic functions of vitamin A may explain the reduction in child mortality? In your answer list which form of vitamin A is involved and what metabolic functions are likely linked to preventing child mortality

Answer 568

Vitamin A as retinoic acid is important in regulating gene expression for cell proliferation and differentiation (important for growth and development) as well as the immune system.

Question 569

What is the physiological aspect of vitamin A metabolism that supports the frequency of a high dose vitamin A supplements (once for infants 6-11 months of age and every 4-6 months for children 12-59 months of age)?

Answer 569

Vitamin A is stored in the liver, and therefore, higher doses every few months can be taken to fill liver stores, which can be released during times when intakes are lower.

Question 570

Describe the rationale for providing recommendations as RAE.

Answer 570

Retinol can be obtained from preformed vitamin A (retinoids) or some carotenoids. RAE accounts for the conversion of carotenoids to retinol and their different contributions to total retinol activity in the body.

Question 571

A vitamin A supplementation is given in an oil-based preparation; if it were given as a non-oil based tablet preparation, would it make a difference for vitamin A absorption? If so, explain why?

Answer 571

Vitamin A is a fat-soluble vitamin that is absorbed with dietary fats; therefore, taking vitamin A with dietary fat will improve its absorption.

Question 572

Describe how vitamin D and parathyroid hormone influence levels of calcium and phosphate in the serum when calcium levels are low. In your answer include all of the organs and processes involved as well as the overall effects of both vitamin D and PTH.

Answer 572

• When calcium is low, PTH is released from the parathyroid.
• In the kidney, PTH promotes activation of vitamin D to calcitriol.
• Calcitriol enhances calcium and phosphate (to some extent) absorption from intestine.
• PTH and calcitriol increase resorption of calcium and phosphate from bone
• Calcitriol increases reabsorption of calcium and phosphate from the kidney
• PTH increases calcium reabsorption but inhibits phosphate resorption in kidney
• The net effect of calcitriol is to increase both calcium and phosphate in serum
• PTH increases calcium but has no net effect on phosphate levels.

Question 573

What hormone is secreted in response to high serum calcium levels and where is this released from?

Answer 573

Calcitonin - released from thyroid gland

Question 574

What additional hormone is secreted in response to high serum phosphate levels and where is this released from?

Answer 574

FGF23 – released from bone (osteocytes)

Question 575

Briefly describe how intracellular calcium is regulated.

Answer 575

Intracellular calcium levels are maintained through a balance of calcium entry into the cell (via calcium channels) and release from the cell (via transporters), as well as regulated storage and release of calcium from organelles.

Question 576

In addition to vitamin D, list one other fat soluble vitamin that is required for calcification of bone.

Answer 576

Vitamin A

Question 577

Compare the digestion and absorption of calcium carbonate and calcium citrate, two forms of calcium found in supplements.

Answer 577

• Calcium carbonate requires acidity for digestion/absorption, so it is advised to take with food since food stimulates HCl production.
• This is not the case for calcium citrate.

Question 578

How are the less commonly consumed forms of selenium absorbed?

Answer 578

Less commonly consumed forms:

Selenate via active transport

Selinite via passive diffusion

Question 579

What are the forms of Mg in supplements? [3]

Answer 579

Mg-citrate

Mg-gluconate

Mg-lactate

Question 580

What are the forms of vitamin E in supplements and fortified foods? [2]

Answer 580

All-racemic α-tocopherol (i.e., all possible stereoisomers of α-tocopherol)

α-tocopheryl acetate

α-tocopheryl succinate

Question 581

What are the forms of zinc in supplements? [2]

Answer 581

Zinc salts (e.g., zinc sulfate, zinc gluconate)

Question 582

What are the forms of copper in supplements? [1]

Answer 582

Copper sulfate and other complexed forms

Question 583

What are the forms of vitamin C in supplements? [4]

Answer 583

Ascorbic acid

Calcium ascorbate

Sodium ascorbate

Dehydroascorbate

Question 584

What are the supplemental forms of selenium? [4]

Answer 584

• Inorganic forms:
  
  • selenide: Se^2- (H₂Se or Na₂Se)
  • selenite: Se⁴⁺ (H₂SeO₃ or Na₂SeO₃)
  • selenate: Se⁶⁺ (H₂SeO₄ or Na₂SeO₄)
• Organic form → selenomethionine

Question 585

What are the supplemental forms of vitamin D? [2]

Answer 585

Ergocalciferol, D2

Cholecalciferol, D3

Question 586

What are the supplemental forms of calcium? [3]

Answer 586

Calcium carbonate

Calcium citrate

…and other salts