The Micronutrients & The B Vitamins

Micronutrients
Vitamins (organic)
- Fat soluble (vitamins A, E, D, and K)
- Water soluble (B vitamins, vitamin C)
Minerals (inorganic)
- Major minerals (larger amounts)
Calcium, phosphorus, magnesium, potassium, sodium,
sulphur and chloride
- Trace minerals (smaller amounts)
Iron, zinc, copper, manganese, iodine, selenium
Vitamins and Minerals
Differ from macronutrients in many ways:
- Structure
Independent units (not linked in chains like starch or
protein)
Minerals are inorganic and are not digested
- Function
Do not yield energy, but frequently assist enzymes
- Food contents
Only small amounts (g to g) needed in diet
Bioavailability
The rate and extent to which a nutrient is absorbed and used
Depends on:
- Efficiency of digestion and/or absorption
- Foods and food components consumed at the same time:
enhancers and inhibitors
- Source of nutrient (synthetic or natural)
- Previous nutrient intake and nutrition status
Precursors
Some vitamins are found in inactive forms in foods;
- Converted to active form inside the body
Important to monitor intake of vitamins AND vitamin precursors
Minerals are often consumed as salts, but these are not considered
precursors
Chemical Nature
Organic nutrients like vitamins can be destroyed (not usable by the
body)
Must be stored and cooked carefully to retain active nutrients
- Wrap foods and store in airtight container
- Refrigerate most fruits and vegetables
- Dont overcook vegetables; consume some raw
Minerals are lost only when boiled out of foods (cannot be destroyed)
Solubility

Hydrophilic (likes water)

- Vitamin C and vitamin B complex (also carbohydrates &
proteins)
- Not stored; kidney excretes excess but can have toxic effects
when huge doses are taken
Hydrophobic (fear of water)
- Vitamins A, E, D, and K (also lipids)
- Stored in adipose tissue
- Can more easily have toxic effects due to build-up in storage
over time

Nutrient Interactions
Presence/absence of one nutrient can affect another nutrients
absorption, metabolism, and excretion
Often excess of one nutrient causes deficiency in another
- When sodium intake excessive, both sodium and calcium
excretion increases
- Supplements, not foods, are often to blame
Toxicity

Amount of Minerals In Body

Micronutrient Roles
Energy metabolism
- B-complex vitamins (water soluble)
- Sulphur (major)
- Iodine, manganese, and chromium (trace)
Electrolytes
- Sodium, chloride, potassium, phosphorus (major)

Micronutrient Roles
Antioxidants
- Vitamin C (water soluble)
- Vitamins A and E (fat soluble)
- Selenium (trace)
Bone health
- Vitamins D and K (fat soluble)
- Calcium, phosphorus, magnesium (major)
- Fluoride (trace)
Blood health
- Vitamin K (fat soluble)
- Iron, zinc, and copper (trace)
Micronutrient Summary
Possible classifications:
- Major or minor (amount in body)
- Essential or dispensable
- Organic or inorganic
- Water or fat soluble (hydrophilic/hydrophobic)
- Role in the body
MANY micronutrients are essential to health
We will cover at least one example from each major role
- Start with micronutrients that assist with macronutrient
metabolism
- Suggestions for micronutrients required for athletic performance
B Vitamins
Thiamin
Riboflavin
Niacin
Pantothenic
Biotin
Vitamin B6
Vitamin B12
Folate
Coenzyme Action

Coenzymes
B vitamins and Metabolism

Form coenzymes
metabolism of the energyyielding nutrients
acid
Amino acids
Cell proliferation

Folate: Biochemistry And Role In Metabolism

Folate Structure

Functions of Folate
Folate is reduced to tetrahydrofolate (THF)
THF functions as co-enzyme to accept one-carbon group (from amino
acid metabolism)
- Sole metabolic function of all the co-enzymatic forms of folate is
to transfer one-carbon units
Amino acid synthesis (regenerates Met from
homocysteine)
Nitrogenous base synthesis (for DNA synthesis)
Forms of Folate Overview

Forms of Folate Biochemistry

Folate
dihydrofolate (DHF)
tetrahydrofolate

(THF)
- Hydrogens added at 5, 6, 7, 8 of folic acid
THF then methylated or formylated

Roles In Amino Acid Metabolism

Methionine Resynthesis

Folate In Nucleotide Metabolism

THF derviatives required for purine and pyrimidine synthesis

Short life-span cells (ie. intestinal cells = enterocytes) very dependent
on folate

Summary of Folates Roles

Essential for amino acid biosynthesis
- Histidine
- Methionine
- Serine
- Glycine
Essential for nucleotide biosynthesis
- Purines
- Pyrimidines
Acts as shuttle for single-carbon transfers
Most important in actively dividing cells like enterocytes
Digestion and Absorbtion
Polyglutamate forms (food) hydrolyzed to monoglutamate
(supplement)
- Glutamate carboxypeptidases
In pancreatic juice and bile (soluble form)
Membrane-bound on intestinal cells (Zn-dependent)
Inhibited by chronic alcohol ingestion
Folate-binding proteins found in membrane of intestinal cells are
saturable and pH, energy, and sodium dependent
- Absorption throughout small intestine
- Supplements may diffuse
Folate Transport in Blood
In blood, folic acid (monoglutamate)
2/3 bound to proteins
- Folate binding proteins (high affinity)
- Albumin, -2 macroglobulin (low affinity)
1/3 free
- Major forms are THF, 5-methyl THF, 10-formyl THF
RBC take up folate only during erythropoiesis
Folate Storage
Uptake by folate receptors of several tissues
Majority stored in liver (~50% of body stores)
- Most common forms THF and 5-methyl THF
- Folylpolyglutamate synthase adds glutamate residues

NOT same as food folate because reduced form (THF) but

similar because of polyglutamate form
Polyglutamate form is better substrate for folatedependent enzymes
Glutamate residues removed by hydrolases before release to blood
- Uptake by other tissues and addition of glutamates before use

Folate Recycling

Excess folate secreted by liver into bile

Travels with bile, with some being
reabsorbed and some excreted
GI tract injuries affect folate needs
- Poor reabsorption of folate by
damaged cells; leads to further damage

Summary: Folate Uptake/Transport

Cyclic conversion of form between mono- and poly-glutamate forms
- Somewhat like cycling of fatty acids on and off the triglycerides
Polyglutamate forms:
- Folate polyglutamate form found in food
- THF polyglutamate best form as enzyme cofactor
Monoglutamate forms:
- Folate monoglutamate (folic acid) taken up by folate-binding
proteins (transporters) on BBM
- THF monoglutamates circulate in blood
Folate RDAs
Adult Males
- 400 g/day
Adult Females
- 400 g/day
- If pregnant or possible to become pregnant, at least 400 g/day
from food PLUS 400 g/day from a supplement
Adequate folate is protective against neural tube defects
in developing fetus
Critical in first 4 weeks (might not realize pregnancy yet)
- If lactating, also increase
For men & women, indicators include:
- erythrocyte folate
- plasma homocysteine
- serum folate
- hematological status
- Body content ~11-28 mg

Folic acid supplements help prevent birth defectswhen taken before

conception

Upper Limit Of Folic Acid Intake

No reports of folate overdose from food
Upper limit (UL) refers to folic acid supplements only
- 1 mg/day maximum
- Based on neurological symptoms of patients with vitamin B 12
deficiency receiving high folic acid
Higher folic acid may be prescribed for women with previous children
with neural tube defects
Sources of Folate

Folic Acid Fortification

Folate and Cardiovascular Disease

High blood homocysteine is a risk factor for CVD, and could indicate
low folate

Folate and Cancer

Complicated relationship; likely related to epigenetic effects due to
methylation of DNA

Sufficient folate protect against the initiation of cancer, but may

enhance progression
- Reduce risk of pancreatic and colorectal cancer
- Increase risk of postmenopausal breast cancer in women with a
specific genotype
Chemotherapy treatment can cause folate deficiency

Folate-Deficiency Anemia
Folate is required for RBC formation
- Deficiency interferes with cell division due to problems with DNA
synthesis and repair
Abnormally large RBCs = macrocytic anemia
- May have nuclei (abnormal)
Causes:
- Poor dietary folate intake
- Alcoholism
- Surgeries affecting stomach/small intestine
- Crohns or celiac disease, other disorders affecting nutrient
absorption
- Certain medications (eg. trimethoprim) which affect folate
Incidence: ~ 1/25,000 people
Folate-Deficiency Anemia

RBCs enlarged (=macrocytic)

RBCs oval instead of round
RBCs might have nuclei

Deficiency in Early Pregnancy

Neural Tube Defects
Spinal cord normally enclosed in the vertabrae
Closure of neural tube in embryo from 21-28 days post-fertilization
- No missed menstruation cycle yet! Many women do not yet
realize that they are pregnant
Forms of neural tube malformations:
- Anencephaly
- Meningocele
- Myelomeningocele (spina bifida)
Incidence varies, ~1-9/1000
- Genetic factors (3-5% multifactorial)
Fetal Development

Normal Spine

Meningocele

Tumor-like sac filled with cerebrospinal fluid

Spinal cord remains within the vertebrae
Often have difficulty with bowel/bladder control, but no
paralysis

Myelomeningocele

Severe form
Spinal cord protrudes through vertebrae
Paralysis ranges from mild to complete
- Loss of bladder/bowel function

Neural Tube Defects

Possible Folate Deficiency Effects

Macrocytic anemia

Cardiovascular disease
Neural tube defects (in developing fetus)
Women capable of becoming pregnant should take folic acid
supplements

B Vitamins: Vitamin B12

B Vitamins and Metabolism

Vitamin B12 is involved in regenerating tetrahydrofolate (THF) to its

active form, and requires THF for its own activation

Folate & B12 Activation

Vitamin B12s Roles

With aid of folate, vitamin B12 is required for:
- Regeneration of methionine (essential amino acid
- Nucleotide biosynthesis (both DNA and RNA)
Without need for folate, vitamin B12:

Maintains sheath around nerve fibres

Assists bone cell activity and metabolism

Vitamin B12 Digestion & Transport

Stomach
- Hcl and pepsin release vitamin B12 from proteins
- Secretes intrinsic factor (a protein)
Small intestine
- Free vitamin B12 is bound by intrinsic factor
- ONLY B12+ intrinsic factor complex absorbed by enterocytes
Bloodstream transports B12 on carrier proteins
Vitamin B12 Recycling

Vitamin B12 secreted by liver into bile

Travels with bile, with some being reabsorbed and some excreted
Most vitamin B12 is reabsorbed, so deficiency is uncommon even when
dietary intake is quite low

Vitamin B12 RDA and Sources

Adults 2.4 g/day
Food sources:
- Animal-derived foods
- Highest bioavailablity from milk and fish
1 cup milk (1 food guide serving) = 1.1 g
75 g salmon (1 food guide serving) = 5.5 g
Vegans possibly at risk
- Use vitamin B12-fortified soy milk or vitamin B12 supplements
Vitamin B12 Deficiency
Primary deficiency (inadequate dietary intake)
- Uncommon because RDA low
- Even vegans make take several years to show symptoms
because of body recycling of B12
Secondary deficiency (inability to absorb/utilize the vitamin B 12 in the
diet)
- More common cause
- Lack of HCl or intrinsic factor stop absorption of vitamin B 12
Secondary Vitamin B12 Deficiency
Common among elderly

Atrophic gastritis damages stomach cells

May also develop due to iron deficiency or infection with
Helicobacter pylori (ulcer-associated bacteria)
- Damaged cells fail to make enough HCl and intrinsic factor, so
B12 is not absorbed even though it is adequate in the diet
Defective gene for intrinsic factor can make absorption impossible
- Must give supplements by injection or nasal spray

Vitamin B12 Deficiency Symptoms

Pernicious anemia
- Destructive anemia due to lack of intrinsic factor and therefore
vitamin B12 deficiency
- Identical to macrocytic anemia from folate deficiency
Same disease because B12 is required to make folate
active; thus B12 deficiency shares symptoms with folate
deficiency
Rapidly dividing blood cells are among first to be affected
(then GI tract)
Macrocytic Anemia

Vitamin B12 Deficiency Symptoms

Macrocytic anemia symptoms can be corrected by supplementing B 12
OR folate
- High folate intake will result in increased active folate
coenzymes
- This can mask vitamin B12 deficiency
Neurological degeneration
- Only vitamin B12, not folate, maintains neuron sheath
- Impaired cognition to creeping paralysis
Vitamin B12 Toxicity
No adverse effects observed for excess
No UL set
B Vitamins: Vitamin B6

Three forms
- Pyridoxal

Pyridoxine
Pyridoxamine

B Vitamins and Metabolism

Vitamin B6 Roles (as PLP)

Amino acid metabolism

- Transfers amino groups (NH2) from amino acids to keto acids
- Conversion of tryptophan to niacin or to serotonin
Synthesis of heme, nucleic acids, and lecithin
Influences cognitive performance, immune function, steroid hormone
activity

Vitamin B6 DRI
Adult RDA 1.3 g/day
Large does of B6 do not enhance muscle strength or physical
endurance
- Claims sometimes made because of B6s involvement in amino
acid metabolism
Does not treat carpal tunnel syndrome
UL of 100 mg/day
- Results in irreversable neurological damage
Food Sources of Vitamin B6

B Vitamins: Riboflavin

B Vitamins and Metabolism

Riboflavin Coenzyme FAD/FADH2

Riboflavin Recommendations
Adult RDA (most Canadians meet or exceed):
- Females 1.1 mg/day

- Males 1.3 mg/day

Deficiency
- Called ariboflavinosis
- Inflammation of membranes of mouth, eyes, skin, and GI tract
Toxicity
- No UL established; no known harm

B Vitamin Deficiency

Riboflavin Sources
Milk and Alternatives are best food group
Dark green, leafy vegetables (broccoli, asparagus, spinach) are good
vegan choices
Ultraviolet light & irradiation destroy riboflavin
- Store milk in opaque plastic, not clear
Stable to heat, so cooking does not destroy riboflavin
Riboflavin Sources

Riboflavin & B6 Interactions

Flavin mononucleotide (FMN, a riboflavin-based coenzyme) is required
for the activation of B6 to its coenzyme form, pyridoxal phosphate
(PLP)
- Severe riboflavin deficiency can impair vitamin B 6 functions
Riboflavin, vitamin B6, and iron are required for the conversion of
tryptophan (aa) to niacin (B vitamin)
B Vitamins: Niacin
Two forms:
- Nicotinic acid
- Nicotimamide

B Vitamins and Metabolism

Niacin Recommendations
Unique among B vitamins: can by synthesized by the body from
tryptophan
- Only after Trp has met protein synthesis needs
- Inefficient: 60 mg Trp yields about 1 mg niacin
Niacin equivalents (NE) used as units
- 1 mg niacin or 60 mg Trp
Adult RDA for niacin (most Canadians meet)
- Females 14 NE mg/day
- Males 16 NE mg/day
Niacin Deficiency
Pellagra
- four Ds
- diarrhea, dermatitis, dementia, and death
Originally thought to be an infection, but eventually shown to be
caused by poor diet
- More common when protein intake limited (Trp)
Pellagra dermatitis
- Photosensitive
- Casals necklace
Common in US in 1900s
- Poor diet rich in corn, low in protien (therefore poor
source of Trp or niacin)
- Corn high in leucine, which can interfere with Trp
niacin conversion
Niacin Toxicity
Not dangerous from foods
Overuse of supplements cause niacin flush
- Nicotinic acid at 3-4 times the RDA dialates capillaries and
causes painful tingling sensation
Nausea, vomiting; liver damage; impaired glucose tolerance
High nicotinic acid can lower LDL, raise HDL and thus protect against
heart disease
Niacin Sources

Meat, legumes, enriched and whole grains

Mushrooms, potatoes, tomatoes are among best vegetable sources
Heat stable, so not damaged by most cooking
Can be lost during boiling (like all water-soluble vitamins)

Niacin Sources

B Vitamins: Thiamin

Forms coenzyme called thiamin pyrophosphate (TPP)

- Required to form acetyl CoA from pyruvate
- Important TCA cycle itself
- Present nerve cell membrane
B Vitamins and Metabolism

Thiamin Recommendations
Essential to consume pre-formed in diet
Average Canadian diet meets or exceeds need
Adult RDA
- Females 1.1 mg/day
- Males 1.2 mg/day

Thiamin Deficiency
Alcoholism can increase chance of thiamin deficiency because it
impairs thiamin absorption and increases excretion
- Estimated 4/5 alcoholics thiamin deficient
Common when protein-poor diet eaten, especially if based on
polished (white) rice (no germ or bran)
Prolonged deficiency causes beriberi
Beriberi Forms

Wet causes edema (swelling), affects mainly cardiovascular system

- Dialated blood vessels, kidneys retain salt and water
Dry causes muscle weakness in arms & legs, affects mainly nervous
system

Thiamin Toxicity
No adverse effects documented
No UL set
Thiamin Sources

Found in many diverse foods, especially pork and milk

Also enriched grains for vegans
Cooking can destroy thiamin
- Steam or microwave heating conserves thiamin
Boiling can remove thiamin because it leeches into the cooking water

B Vitamins: Biotin

In TCA cycle adds a carbon to pyruvate to replenish oxaloacetate

Required gluconeogenesis, fatty acid synthesis, and breakdown of
certain fatty acids and amino acids
B Vitamins and Metabolism

Biotin Recommendations etc.

Adult AI is 30 g/day
Biotin deficiency
- Rare, but can be induced by feeding >24 raw egg whites /day
over several months (cooking denatures avidin, the binding
protein that prevents biotin absorption)
- Symptoms: skin rash, hair loss, neurological impairment
Biotin toxicity is not documented; no UL set
Biotin Food Sources
Widespread in foods (even egg yolks)
- Liver, soybeans, fish, whole grains
Some synthesized by commensal gut bacteria
B Vitamins: Pantothenic Acid

Part structure coenzyme A

- (From acetyl CoA)

B Vitamins and Metabolism

Pantothenic Acid Recommendations etc.

Adult AI 5 mg/day
Pantothenic acid deficiency
- Rare
- Symptoms involve failure of all body systems and include
fatigue, GI distress, neurological disturbances

Burning feet of prisoners of war in Asia in WWII

Pantothenic acid toxicity
None reported, no UL set

Pantothenic Acid Sources

Widespread in foods, most diets sufficient
- Beef, poultry, whole grains, potatoes, tomatoes, and broccoli are
good sources
Easily destroyed by food processing
- Raw foods are best source
B Vitamins: Coenzymes for Energy Metabolism

B Vitamin Overview

Micronutrient Summary
Possible classifications:
- Major or minor (amount in body; minerals)
- Essential or dispensable
- Chemical nature: organic or inorganic
- Water or fat soluble (hydrophilic/hydrophobic)
- Role in the body
Precursors
Bioavailability
Micronutrient: B Vitamins
All are organic (issues regarding degradation)
All are water soluble (hydrophilic)
All play a role in energy metabolism
- But the exact contribution varies
All are essential

Yes, even niacin (can be made from Trp, which is essential too)

Micronutrient: B Vitamins
Precursors
- Trp is converted to niacin (requires riboflavin, B 6, and iron)
Bioavailability
- Food folate (polyglutamate) vs. supplemental folic acid
(monoglutamate; 1.7 times more available)
- B12 found in animal products; inactive form in yeast, miso, sea
algae