Nutrition Basics: Micronutrients

]]Define the terms: vitamin and mineral.]]
- ==Vitamins== - organic essential nutrients required in tiny amounts to perform specific functions that promote growth, reproduction, or the maintenance of health and life. Both fat soluble and water soluble.
  - Properties of fat soluble - stored in the body so deficiencies appear more slowly. Greater potential for toxicity.
  - %%Vitamins A, D, E, K%%
  - Properties of water soluble - excess is secreted because most are not stored. Deficiencies may appear more quickly.
  - %%B-vitamins, Vitamin C%%
- ==Minerals== - inorganic, essential nutrients required in varying amounts that function primarily as structural components or regulators of body processes
  - E.g. calcium, magnesium, potassium (macrominerals)
  - E.g. iron, zinc, fluoride, chromium (microminerals)
]]Explain the difference between enrichment and fortification.]]
- %%Enrichment%% - addition of nutrients to replace those lost in food processing
- %%Fortification%% - addition of nutrients to foods that didn’t have them in the first place
]]Discuss circumstances when it might be suitable to supplement with vitamins and/or minerals.]]
- Vitamin and mineral needs should usually be met by eating a balanced diet with a variety of foods
- Health Canada fortifies many foods in an effort to prevent nutritional deficiencies
  - Vitamins A + D → added to milk and margarine
  - B vitamins + iron → added to enriched flour
  - Iodine → added to table salt
- Supplements might be recommended when:
  - Requirements are increased
  - Difficult to obtain sufficient amounts from diet (e.g. pregnant/lactating women → folic acid, iron)
  - Drug-nutrient interactions
  - Smokers (vitamin C)
  - Intake from diet is likely inadequate
  - People on low calorie diets (<1600 kcal/day)
  - Those who avoid entire food groups (vegetarians/vegans)
  - Chronic substance abuse
  - Elderly with a poor diet
  - Lactose intolerant (may need calcium)
  - Malabsorption is a risk
  - Following bariatric surgery (e.g. gastric bypass, weight loss surgery)
  - GI diseases known to cause malabsorption (e.g. cystic fibrosis)
  - Elderly
  - Therapeutic uses
  - Correction of a deficiency (UL do not apply)
  - To prevent or treat a disease or condition unrelated to a deficiency (e.g. Vit B6 for CV disease, Vit C for cold)
]]For each nutrient be able to discuss its: chemical name of active substances/forms (if given); physiological function in the body; symptoms of deficiency and explain circumstances under which this might occur; adverse effects associated with excess intake; therapeutic use and evidence (other than to correct a deficiency)]]
- ==Anti-oxidant vitamins==
  - %%Vitamin A and beta-carotene%%
  - Sources: animal (vitamin A - preformed), plant (carotenoids - most potent is B-carotene (precursor form))
  - 3 forms of vitamin A are active in the body, each with a different role. Collectively called retinoids
    - Retinol (used in reproduction)
    - Retinal (used in vision)
    - Retinoic acid (used to regulate growth)

* Beta-carotene from supplements is better absorbed than that from diet * Some carotenoids (e.g. lutein, lycopene) have no vitamin A activity (i.e. won’t produce retinol) * Physiological function: * Promote vision (esp. night vision) → in the retina, vitamin A in the form of retinal makes rhodopsin, a light sensitive pigment that carries visual information to the brain * Maintains the health of epithelial tissue and skin (via protein synthesis and cell differentiation) → growth * Fetal development, growth and cell differentiation → reproduction * Supports overall immune function * Beta-carotene: can convert to vitamin A (in the intestinal mucosa and liver), or if unconverted, has anti-oxidant properties * Deficiencies: * Very rare in North America, but common in undeveloped countries (in association with malnutrition) * Night blindness: without Vitamin A in the diet (→ liver stores get exhausted), this cycle comes to a halt because there is not enough retinal in the retina to regenerate rhodopsin, and the ability to see in low light decreases * Toxicity and effects: * Intake > 1500 mcg (2x the RDA) is associated with decreased bone density and increased risk of fracture in adults → can lead to osteoporosis * Teratogenic → if excess of 10,000 IU or 3,000 mcg/d are taken during the first 2 months of pregnancy → increases chance of birth defects @@(AVOID)@@ * Therapeutic uses: * Vitamin A - only in the correction of a deficiency * %%Beta-carotene:%% * Investigated due to anti-oxidant activity (but no benefit in reducing risk of cancer or CVD) * 2 studies found increased risk of lung cancer in smokers * Increased risk in total mortality * Used for ^^treatment of macular degeneration^^ * %%Vitamin E%% * 8 naturally occurring anti-oxidant forms (called tocopherols) * Alpha-tocopherol is the only form that our bodies can use; found in circulation and tissues * Alpha-tocopherol and Vitamin E are used interchangeably * Dietary sources of alpha-tocopherol: vegetable oils, nuts, meat, poultry, eggs, and whole grains (food high in FAT) * Synthetic (dl-a-tocopherol) → 8 isomers (only ½ are active in body) * Natural (d-a-tochopherol) → provides twice the biological activity as synthetic form * Supplements: * Made from both synthetic and natural Vit E * Content expressed IU * Synthetic Vit E contains less of the active form, often sold in higher doses * Physiological function: * No metabolic function * Lipid-soluble anti-oxidant * Protect cell membranes against oxidative damage by free radicals * Protects lipids from oxidation * Deficiencies: * Very rare; may be found with diseases of fat malabsorption (such as cystic fibrosis) * Toxicity and effects: * Risk of bleeding at higher doses (especially with synthetic form); and, * Vitamin E and warfarin together have been observed to increase risk of bleeding * Therapeutic uses: * May slow the progression of ^^Alzheimer’s Disease^^ by 6 months → no evidence for prevention of dementia * CVD → results have been largely negative, with some harmful outcomes (increased risk of heart failure, mortality, stroke) * Wound healing/scar prevention (topical) → not shown to be effective * Cancer → 400 IU of Vit E every other day did not reduce the overall risk of cancer in men * may actually increase risk of prostate cancer → supplements, not foods * ^^BOTTOM LINE: supplementing may actually be harmful^^ * %%Vitamin C%% * Also known as ascorbic acid * Physiological function: * Act as coenzyme involved in collagen synthesis (helps with wound healing), carnitine production, and neurotransmitter (noradrenaline) formation * Act as an anti-oxidant * Defends against free-radicals (or neutralizes free radicals) * Protects tissues from oxidative damage, so may help prevent diseases * Regenerates other antioxidants within the body (e.g. Vitamin E) * Deficiencies: * Severe deficiency, scurvy is uncommon (need Vit C intake to be

==Nutrients for metabolism==
- %%B vitamins%%
  - Help body use fuel from energy-yielding nutrients (carbs, fats, proteins)
  - Can work individually and interdependently
  - 8 essential B vitamins
    - %%Thiamine (B1)%%
    - Dietary sources:
      - Whole grain products, legumes (e.g. beans and lentils), nuts, meat (esp. pork) and yeast
      - Canada → wheat flour is fortified with thiamine
      - Lost during production of white flour and white rice
    - Physiological function:
      - Essential co-enzyme (thiamine pyrophosphate - TPP) used in carb and amino acid metabolism
      - Required for the formation of acetyl-CoA from pyruvate and ATP generation
    - Deficiencies:
      - Dietary (developing countries)
      - Rare in Western countries due to consumption of whole grain products (exceptions: malnourished (homeless), alcohol abuse)
      - Beriberi - condition that can happen after prolonged deficiency which can result in both neurological (peripheral neuropathy) and cardiac symptoms (heart failure)
      - Wernicke-Korsakoff Syndrome - severe deficiency caused by alcohol abuse (impairs thiamine absorption and increased excretion in urine). Symptoms include: jerky eye movements and motor abnormalities
    - Therapeutic uses:
      - Prevention and treatment of thiamine deficiency
      - Other uses under investigation: Alzheimer’s disease, Diabetes
      - Marketed to provide “more energy” → does provide ATP but doesn’t increase energy levels (unless you are deficient)
    - No UL; no known toxicity
    - %%Riboflavin (B2)%%
    - Dietary sources:
      - Found in many different foods in small amounts; milk, yogurt, fortified cereal, beef, enriched grains
    - Physiological function:
      - converted to coenzymes FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide) - FAD is part of electron transport chain that produces ATP
      - Involved in the activation + metabolism of vit B6, folic acid, niacin (other B vitamins) to their active forms in the body (example of interdependency)
    - Deficiencies:
      - Rarely happens because it’s recycled in the body and widely available in foods
    - Therapeutic use:
      - ^^Migraine prophylaxis^^ - taking high dose (400mg/day) for 3 months can decrease frequency and number of headache days
    - %%Niacin (B3)%%
    - Dietary sources:
      - Milk, eggs, meat, poultry, fish, whole-grain, fortified cereals, nuts and all protein containing foods
    - Physiological function:
      - The coenzymes NAD and NADP are required in many oxidative-reduction reactions including glycolysis. Helps body to metabolize carbohydrates, fats, and proteins.
      - Both niacin forms are converted to the niacin coenzyme
    - Deficiencies:
      - Pellagra - inability to absorb niacin may cause this. Dermatitis, diarrhea, and dementia (if left untreated - death)
      - Secondary deficiency can occur from malabsorption (chronic alcohol abuse, anorexia, prolonged diarrhea)
    - Toxicity and effects:
      - when used in high doses may see pruritus, GI distress, and abnormal liver function
      - When taken at therapeutic levels to resolve hyperlipidemia, common adverse effects including flushing and other vasodilation symptoms (flushing can be reduced by ASA or NSAIDs before niacin dose)
    - Therapeutic uses:
      - Effective at ^^lowering LDL^^ and ^^increasing HDL^^
      - ^^Treatment of Pellagra^^
    - %%Pantothenic acid (B5)%%
    - %%Pyridoxine (B6)%%
    - Dietary sources:
      - Meats, fish, poultry, bananas, and blueberries, fortified cereals
    - Occurs in 3 forms: Pyridoxine, pyridoxal, pyridoxamine → all 3 can be converted to co-enzyme ^^pyridoxal phosphate (PLP)^^
    - Physiological function:
      - PLP acts as a co-enzyme used in amino acid, glycogen and fatty acid metabolism (a co-factor for more than 100 enzymes)
      - Helps to convert tryptophan to niacin and serotonin
      - B6, B12 and folate → work together to lower homocysteine levels
      - Helps to make RBCs
    - Deficiencies:
      - It synthesizes key neurotransmitters
      - Early signs of B6 deficiency include depression and confusion
      - Low levels of B6 have been associated with increased risk of some cancers and CV disease
      - Can be drug induced
    - Toxicity and effects:
      - High doses B6 (>20 mg/day) and B12 (>55 mcg) have been associated with increased risk of lung cancer by 2-fold (in men only and greater in smokers)
      - Can cause sensory neuropathy with intakes >200 mg/day for several months
    - Therapeutic uses:
      - ^^Pre-menstrual syndrome (PMS)^^ - 50-100 mg/day may be of value to treat PMS, mostly mood symptoms
      - Depression - benefit is questionable, although in seniors it did show decrease in depression symptoms
      - ^^Morning sickness^^ - somewhat effective for nausea in pregnancy
      - ^^CVD^^ - elevated homocysteine can lead to heart disease. Studied alone and in combo with B12 and folic acid - mixed evidence.
    - %%Biotin (B7)%%
    - Part of a co-enzyme used in energy metabolism, fat synthesis, amino acid metabolism and glycogen synthesis
    - Food sources: yogurt, nuts, eggs, salmon, sweet potatoes
    - Also produced by GI bacteria
    - Deficiency:
      - Extremely rare - skin rashes, thinning hair and brittle nails
    - Therapeutic uses:
      - ^^Brittle nails^^ - may improve nail thickness and splitting of brittle nails
      - ^^Hair growth and improving skin^^ - only in children + case reports
    - %%Folic acid (B9)%%
    - %%Cobalamin (B12)%%
    - Dietary sources:
      - exclusively animal sources: meat, fish, poultry, milk, cheese, eggs; fortified foods like cereal
      - Our ability to absorb from dietary supplements is limited by the capacity of intrinsic factor - only about 10 mcg of a 500 mcg oral supplement is actually absorbed in healthy people
      - ^^Stomach acid and intrinsic factor^^ are required for the absorption of B12
    - Physiological function:
      - Interdependent role with folate (coenzyme in folate and fatty acid metabolism)
      - Required for normal nerve function
      - Assists hemoglobin and red cell production
      - Lowers homocysteine levels
    - Deficiencies:
      - elderly
      - Pernicious anemia (lack of intrinsic factor) - main cause
      - Atrophic gastritis (decrease in stomach pH)
      - Vegan diet
      - It could take up to 3 years once eliminating animal sources due to recycling of B12 in the body
      - Surgery in the GI tract
      - GI disorders (Celiac, Chron’s)
      - Can be drug induced
    - Toxicity and effects:
      - No UL; no known toxicity
      - High doses - increased risk of lung cancer (men and smokers)
    - Therapeutic uses:
      - Treatment of vitamin B12 ^^deficiency^^ in patients with pernicious anemia, malabsorption disorders of neurological involvement
      - People at risk of deficiencies: elderly, vegans or strict vegetarians
      - Because 10-30% of older people don’t absorb food-bound B12, those ^^>50 y/o are advised to supplement^^
      - May decrease risk of developing ^^age-related macular degeneration^^ when combined with B6 + folic acid
      - Energy and endurance - no beneficial effect on performance in the absence of a nutritional deficit
      - ^^CVD^^
==Nutrients for bone health==
- %%Calcium%%
  - Dietary sources:
    - Mainly from milk and dairy products
    - Green leafy vegetables (broccoli, bok choy, kale)
    - Salmon and sardines
  - Physiological function
    - \ > 99% of calcium is stored in bone, which acts as a reservoir and helps with bone structure
    - Required for: cell signalling, current flow across excitable membranes, muscle contraction, blood coagulation, formation structure and remodelling of the skeleton (bone growth and density)
    - VERY IMPORTANT that calcium levels in blood and ECF be maintained within very narrow limits to support normal physiological functions
    - Regulated by PTH and calcitonin (regardless of dietary intake)
    - When plasma Ca2+ levels are low, the bones suffer (PTH pulls from bone)
    - Requires adequate levels of vitamin D
  - Deficiencies
    - Silent (no symptoms) - also blood calcium remains normal
    - If chronic inadequate intake:
    - May prevent attainment of peak bone mass (i.e. max calcium stores)
    - May contribute to accelerated bone loss and development of osteoporosis
  - Toxicity and effects:
    - High doses can cause kidney stones
    - Most common: constipation (Mg can offset this - but too much causes diarrhea)
    - Calcium-alkali syndrome: caused by very high doses of calcium carbonate, leading to hypercalcemia, vascular and soft tissue calcification, and renal insufficiency
  - Therapeutic uses
    - ^^Dyspepsia^^ (calcium carbonate)
    - ^^Renal failure^^ (calcium acetate + carbonate are phosphate binders)
    - ^^Lactose intolerant^^
    - No evidence for fracture prevention in healthy adults
  - Calcium carbonate (TUMS)
    - 40% calcium content (highest)
    - Needs acidic environment for best absorption - take with food
    - Don’t use if on PPI or H2RA
    - SE: gas/bloating/constipation
    - Absorption is greatest when each dose does not exceed 500mg - recommended divided doses
    - If combined with vit D or K, take with a fatty meal to increase absorption
  - Calcium citrate
    - 21% calcium
    - Absorption independent of stomach pH
    - Larger pills required to get same dose
    - Less side effects
  - Interactions:
    - Decreased absorption of bisphosphonates, levothyroxine, antibiotics (quinolones, tetracycline) - space up to 4 hrs apart
    - Thiazides decrease calcium excretion by the kidneys → hypercalcemia or calcium-alkali syndrome (concern if taking large amounts of Ca carbonate)
    - IV calcium: can cause precipitation of some drugs (e.g. ceftriaxone)
- %%Vitamin D%%
  - Two forms: ergocalciferol (D2) from yeasts and fungi; cholecalciferol (D3) from animal tissues
  - Sources:
    - Formed naturally in the skin on exposure to UVB (endogenous production) - main source
    - Foods: fatty fish (mackerel, salmon, sardines), fish liver oils, egg yolks, or fortified milk
    - Natural Health Products - most are D3
    - All produce calcidiol, which will then go on to produce the active form (calcitriol, a steroid hormone)
  - Production and activation
    - Vit D3 is produced in the skin epidermis then taken to the liver for activation
    - Next, transported to the kidney for secondary hydroxylation to the active form, calcitriol
    - Vit D2 also gets converted to calcidiol - but D2 is less active
  - Physiological function
    - Together with calcitonin and PTH, it regulates plasma calcium - helps support normal bone mineralization, neuromuscular function and cell physiology
    - Also has widespread receptors (brain, prostate, breast, colon, immune cells, etc.)
    - Can regulate the expression of >2500 genes involved in skeletal and other biological functions (e.g. decreases cell proliferation of normal and cancer cells and induces their differentiation)
    - Influences immune cell function
    - Generally lowers inflammation
  - Deficiencies
    - Deficiency is rare but insufficiency is very common
    - Factors that lead to deficiency include:
    - Dark skin (melanin absorbs UVB and competes with vit D)
    - Exclusively breastfed infants without Vit D supplement
    - Lack of sunlight or covering all exposed skin (or using SPF >= 8 or greater when outside)
    - Not using fortified milk
    - In Vancouver, only not getting adequate UV levels in November to February
    - Elderly → deficiency very likely
    - Lose ability to make and activate Vit D
    - Drink less milk
    - Stay indoors more (and cover up when they go outside)
    - \ > ^^51 y/o → take 400 IU of Vit D in supplement form each day (in addition to what they consume through diet)^^
    - Signs of deficiency:
    - Rickets (children)
      - Failure to mineralize new bone
      - Results in soft bones, deformed joints
    - Osteoporosis
    - Osteomalacia - generalized decreased in bone density and mineralization, with muscle weakness, bone pain
  - Toxicity and effects
    - Hypercalcemia (very rare)
    - raises concentrations of blood calcium leading to weakness, fatigue, headache, N/V/D
    - Impaired renal fxn
    - Can lead to: calcification of soft tissues, irreversible kidney failure
    - UL: 4000 IU/day (adults and children)
    - Toxicity is seen at doses >10,000 IU/day
  - Therapeutic uses
    - Osteomalacia
    - Rickets
    - Preventing corticosteroid-induced osteoporosis
    - Osteoporosis
    - URTI
    - Prevention of heart failure in elderly who have inadequate Vit D levels (not useful for treatment of HF)
    - Often recommended in the elderly
- <<NOTE: to go from IU to mcg: divide by 40; To go from mcg to IU: multiply by 40<<
- %%Vitamin K%%
  - 2 compounds:
    - Vitamin K1 (phytomenadione) - plants, green vegetables, kiwi
    - Vitamin K2 (menaquinone) - synthesized by intestinal bacteria
  - Physiological function
    - Coenzyme for Vit K dependent carboxylase - an enzyme required for synthesis of proteins involved in:
    - helping to bind calcium to form bone (calcification) and decreasing bone turnover
    - blood clotting (needed to produce prothrombin)
  - Deficiency and toxicity
    - Both very rare
    - Deficiency:
    - Results in hypoprothrombinemia, leading to an increased tendency to hemorrhage
    - Low bone density (but long term effects on bone health are unknown)
    - In ^^newborns^^ → all get a Vit K injection
    - Toxicity:
    - No adverse effects seen with high intake (no UL needed)
  - Therapeutic uses
    - To overcome excess effects of the coumarin oral anti-coagulants
    - To prevent hemorrhagic disease in newborns
    - Bruising - but no evidence for treatment/prevention
    - Osteoporosis:
    - Findings are mixed with both K1 + K2: some show improved BMD and fracture reduction, other’s don’t
    - Some evidence that a high dietary intake of K1 improves BMD in women (not men)
    - Drug interaction: Vit K antagonists (e.g. Warfarin) - pts need to eat consistent diet (same amount of Vit K day-to-day)

]]List 2 major sources from which each vitamin can be obtained.]]
]]Discuss the clinical implications of the AREDs studies.]]
- %%Age-related Macular Degeneration (AMD)%% is the leading cause of vision loss
- Characterized by:
  - Reduced central vision (not peripheral like glaucoma)
  - Reduced visual discrimination
  - Altered ability to read, drive, recognize faces, etc.
- ^^Age-related Eye Disease Study (AREDs)^^
  - Interventions (4 arms):
  - Anti-oxidants (vitamin C, vitamin E, beta-carotene) alone
  - Anti-oxidants + Zn + Copper
  - Zn + copper alone
  - Placebo
  - Only effective for intermediate to advanced AMD
- AREDS 2
  - Removed the beta-carotene; added 2 other carotenoids (lutein, zeaxanthin); lowered dose of zinc (diarrhea); added Omega-3 fatty acids; only studied people with intermediate or advanced AMD
  - No benefit adding Omega-3; adding lutein/zeaxanthin gave slight benefit (and beneficial to prevent harm in former smokers); lowering dose of Zn produced no change in efficacy
- BOTTOM LINE:
  - taking AREDS or AREDS 2 supplements ^^reduces the risk of progression^^ from intermediate to advanced AMD by about ^^25%^^
  - Do not prevent AMD onset
  - Do not have an effect on cataract
  - Omega-3 → no effect on cataract or AMD
  - Current + former ^^smokers^^ should take the ^^AREDS2^^ formula and avoid the AREDS formula (increased lung cancer risk with beta-carotene)