Micronutrients Flashcards
What two substances make up the category of micronutrients?
Vitamins (organic) Trace elements (inorganic)
What is the definition of micronutrients?
Essential compounds required in very small amounts in the diet
Where are vitamins and trace elements produced?
- Vitamins are organic molecules synthesized by plants and bacteria
- Trace elements are inorganic compounds that were made in ancient stars & supernova explosions…
What are the various roles of micronutrients?
- Structure:
o Phospholipids form complexes with both Mg2+ and Ca2+. These complexes are integral parts of the various membranes in the cell - Genetic Control:
o Control of gene expression - vitamins A and D - Antioxidant:
o Inhibits the oxidation of other molecules – beta-carotene / vitamin C - Coenzymes:
o Small non-protein organic molecule. Cannot by themselves catalyze a reaction but they help enzymes to do so – thiamine pyrophosphate (TPP) - Cofactors:
o Non-protein chemical compound or metallic ion required for a protein’s biological activity to happen – iron / zinc
What are free radicals, from where are they derived and what can they affect?
- Free radicals, both the reactive oxygen species (ROS) and reactive nitrogen species (RNS), are derived from both:
o Endogenous sources (mitochondria, peroxisomes, endoplasmic reticulum, phagocytic cells etc.)
o Exogenous sources (pollution, alcohol, tobacco smoke, heavy metals, transition metals, industrial solvents, pesticides, certain drugs like halothane, paracetamol, and radiation) - They can adversely affect various important classes of biological molecules such as nucleic acids, lipids, and proteins and are linked to many disorders (diabetes, neurodegenerative disorders…)
What are some examples of antioxidants? What are the four steps in which antioxidants work?
- Normal reactions in the body, and stressors such as chemicals in the environment, smoking and ultraviolet light, create free radicals.
- Free radicals have an unpaired electron that seeks an electron from another compound, causing a chain reaction of oxidation.
- Free radicals lead to oxidative stress. This accelerates the aging process and increases the risk of heart disease, cancer, diabetes, arthritis, macular degeneration, Parkinson’s disease and Alzheimer’s disease.
- Antioxidants, such as vitamin E, neutralise free radicals by ‘lending’ an electron to stabilise damaged atoms.
How does vitamin E protect cell membranes?
It is contained in the membrane and neutralises free radicals, preventing them from damaging phospholipids
What is the role of retinoic acid (vitamin A) and how is it produced?
Retinoic acid (Vitamin A) is important in imprinting cells to home to the gut mucosa from Peyer’s patches. Gut dentritic cells (DC) have Retinal dehydrogenases and produce retinoic acid.
What is the role of micronutrients in adults? How is this different to in children?
- Maintain ‘homeostasis’ in adults
- More important in paediatric population
o Energy supply
o Body growth & development
o NB: Healthy young infants require 3x energy per kg body weight than adults - Supply of micronutrients has short and long term health implications
Which micronutrients are particularly important in childhood?
Preventing iron deficiency improves children’s learning ability and cognitive development.
Flour can be fortified with folic acid at low cost, helping prevent birth defects and some forms of anaemia.
Provisions of micronutrients ranked as the world’s best investment for development.
What are the rates of malnutrition in hospitals?
- 13-40% of in-patients
- 28% ‘at risk’ of malnutrition
o 34% acute admissions
o 52% from care homes
o ‘Nil by Mouth’ for ≥5 days (e.g. for operation)
What are two common vitamin deficiencies and what foods do they come from?
Vitamin D - oily fish, dairy products, orange juice
Vitamin B12 - meat and dairy
What is the RDA?
- Recommended Dietary Allowance (RDA)
o Nationally defined
o Observational studies
o Nutrient balance studies
o In vitro / vivo depletion studies
o Intake meets nutritional needs of 98% of individuals - Limits defined for deficiency (too little) or toxicity (too much)
Which vitamins are fat soluble? Can they be stored? What happens when they are in excess?
Vitamins A, D, E and K
Can be stored (e.g. in liver)
Occasionally toxic when in excess
Which vitamins are water soluble? Can they be stored? Any special functions? What happens when they are in excess?
Vitamins B and C
Normally not stored (small amount of B1 in liver)
Excess excreted in urine
How are fat soluble vitamins absorbed?
o Absorbed with lipids as they readily dissolve in lipid droplets, micelles and chylomicrons.
Go straight to lymph fluid
How are water soluble vitamins absorbed?
o Most water-soluble vitamins (B, C) follow the flux of water from the gut lumen through the mucosa.
Go straight to portal vein
How is the microbiome related to vitamins?
- Commensal bacteria are both providers and consumers of B vitamins and vitamin K.
- Scientific studies emphasized the requirement for increased dietary vitamins K, B1 (thiamin), B6 (pyridoxine), B7 (biotin), B9 (folic acid), and B12 (cobalamin) for the health of germfree animals.
What are possible reasons for decreased vitamin intake in developed countries?
o Alcohol dependency: Chiefly B vitamins (Vit B1)
o Vegans: Vit D (if no sunshine); Vit B12
o Elderly with poor diet: Chiefly Vit D (if no sunshine); Folate (Vit B9)
o Anorexia: Chiefly Folate (Vit B9)
What are possible reasons for decreased vitamin absorption in developed countries?
o Any malabsorptive state (coeliac disease): Chiefly Folate (Vit B9)
o Ileal disease / resection: Only Vit B12
o Liver and biliary tract disease: Fat soluble Vit
o Intestinal bacterial overgrowth Vit B12
o Oral antibiotics: Vit K
What are signs of protein-energy malnutrition?
Alopecia
Brittle hair
Hair changes colour
Hair easily pluckable
What are signs of Vitamin E deficiency?
Dry hair
What are signs of Vitamin A deficiency?
Dry hair Acneiform lesions Follicular keratosis Xerosis (dry skin) Bitot's spots on eyes Conjunctival xerosis, keratomalacia
What are signs of Vitamin C deficiency?
Ecchymosis
Intradermal petechia
Bleeding gums
What are signs of Vitamin K deficiency?
Ecchymosis
Intradermal petechia
What are signs of niacin deficiency?
Erythema (especially when exposed to sunlight) Hyperpigmentation Seborrheic dermatitis Scrotal dermatitis Atrophic papillae Glossitis
What are signs of Vitamin D deficiency?
Genu valgum or varum, metaphyseal widening
What are signs of vitamin B2 deficiency?
Seborrheic dermatitis (nose, eyebrows, eyes) Scrotal dermatitis Angular palpebritis Corneal revascularisation Angular stomatitis Cheilosis Glossitis Magenta tongue
What are signs of vitamin B6 deficiency?
Seborrheic dermatitis (nose, eyebrows, eyes) Scrotal dermatitis Cheilosis Angular stomatitis Glossitis
What are signs of vitamin B12 deficiency?
Angular stomatitis
Glossitis
Loss of deep tendon reflexes of the lower extremities
What are signs of vitamin B1 deficiency?
Loss of deep tendon reflexes of the lower extremities
What are the most common causes of deficiency of the fat soluble vitamins?
Fat malabsorption
Alcoholism
Liver disease
What are the most common causes of deficiency of the water soluble vitamins?
Alcoholism, any malabsorptive state, drugs
What is the RDA for vitamin A? What are contributing factors to, and main clinical features of, deficiency?
RDA = 700-900 micrograms/day
Contributing factors = infections, measles, protein-energy malnutrition
Clinical features = xerophthalmia
What is the RDA for vitamin D? What are contributing factors to, and main clinical features of, deficiency?
RDA = 5-15 micrograms/day
Contributing factors = aging, lack of sunlight exposure
Clinical features = rickets, osteomalacia
What is the RDA for vitamin E? What are contributing factors to, and main clinical features of, deficiency?
RDA = 15 milligrams/day
Contributing factors = antibiotic use
Clinical features = peripheral neuropathy
What is the RDA for vitamin K? What are contributing factors to, and main clinical features of, deficiency?
RDA = 90-120 micrograms/day
Contributing factors = antibiotic use
Clinical features = coagulopathy
What is the RDA for vitamin C? What are contributing factors to, and main clinical features of, deficiency?
RDA = 75-90 milligrams/day
Contributing factors = smoking
Clinical features = scurvy
What is the RDA for vitamin B1? What are contributing factors to, and main clinical features of, deficiency?
RDA = 1.1-1.2 milligrams/day
Contributing factors = concommittant vitamin B6, B12 and folate deficiency
Clinical features = Beri beri
What is the RDA for vitamin B2? What are contributing factors to, and main clinical features of, deficiency?
RDA = 1.1-1.3 milligrams/day
Contributing factors = malabsorption
Clinical features = angular stomatitis
What is the RDA for vitamin B3? What are contributing factors to, and main clinical features of, deficiency?
RDA = 14-16 milligrams/day
Contributing factors = vitamin B6 deficiency, riboflavin deficiency
Clinical features = pellagra
What is the RDA for vitamin B6? What are contributing factors to, and main clinical features of, deficiency?
RDA = 1.3-1.7 milligrams/day
Contributing factors = isoniazid use
Clinical features = neuropathy, anaemia
What is the RDA for vitamin B12? What are contributing factors to, and main clinical features of, deficiency?
RDA = 2.4 micrograms/day
Contributing factors = gastric atrophy (pernicious anaemia), terminal ileal diseasem strict vegetarianism
Clinical features = anaemia
What is the RDA for folate? What are contributing factors to, and main clinical features of, deficiency?
RDA = 400 micrograms/day
Contributing factors = sulfasalazine, pyrimethamine, triamterene
Clinical features = anaemia
What are trace elements? What are six important examples?
- “Dietary minerals that are necessary, in very minute quantities, for the normal function of the organism”
Calcium, phosphorus, iron, selenium, zinc, copper
What are the sources and function of calcium, and what are the effect of deficiency?
Source = Dairy products Function = Mechanical stability of skeleton, neuromuscular activity, signal transduction Deficiency = Osteoporosis, parathesia, muscle spasms
What are the sources and function of phosphorus, and what are the effect of deficiency?
Source = Seeds/nuts, lentils, soya Function = Components of structural proteins, enzymes, transcription factors, ATP and nucleic acids Deficiency = Bone pain, pseudofractures, and proximal muscle weakness, or rickets and short staure in children, neurological manifestations
What are the sources and function of iron, and what are the effect of deficiency?
Source = Red meat, dark vegetables, watermelon Function = Part of the haem protein and enzymes Deficiency = Anaemia
What are the sources and function of selenium, and what are the effect of deficiency?
Source = Seafood, red meat and cereal Function = Component of glutathione peroxidase and deiodinase enzymes Deficiency = Rare in UK, cardiomyopathy can occur
What are the sources and function of zinc, and what are the effect of deficiency?
Source = Meat, shellfish, nuts and legumes Function = Synthesis and stabilisation of proteins, DNA and RNA; normal spermatogenesis, fetal growth and embryonic development Deficiency = Growth retardation, alopecia, dermatitis, diarrhoea, congenital malformations
What are the sources and function of copper, and what are the effect of deficiency?
Source = Shellfish, liver, nuts, legumes, bran and offal Function = Part of numerous enzymes for iron metabolism; melanin, elastin and collagen synthesis; central nervous system function Deficiency = Growth retardation
What is iron essential for?
- Oxygen transport within haemoglobin
- Myoglobin function in skeletal muscle
Where and how is iron absorbed?
- Absorbed in the upper small bowel
o Transferrin (iron protein transport is serum)
o Iron is stored in liver and bone marrow as ferritin
o Be aware of haem chelaters (used to prevent Iron overload / oxidative damage in patients)
Which clinical conditions can be caused by a deficiency in iron?
Microcytic anaemia
Lethargy and fatigue (adults)
Cognitive impairment (children)
Exacerbation of inflammatory states
What clinical conditions can be caused by an excess of iron?
Haemochromatosis
- Lethargy/fatigue
- Abdo/joint pain
- Reduced libido
- Bronzing of skin
- Diabetes
- Cirrhosis
- Cardiomyopathy
What are the three types of vitamin D?
- Calciferol o Ergocalciferol (D2) o Cholecalciferol (D3) - Calcidiol o 25-hydroxyvitamin D - Calcitriol o 1α, 25-dihydroxyvitamin D
How much sunlight does a caucasian need for sufficient vitamin D? How about non-caucasion? Does the UK weather allow for this? Why must we be careful with sun exposure?
- Caucasians
o 20-30 minutes of sunlight ≈ 2,000 iU Vitamin D
o Two or three exposures a week during summer - Non-causcasian
o Require 2-10 times the exposure - UK has insufficient UVB between October and March
- Sunscreens ≥ SPF15 block 99% dermal Vitamin D synthesis
- Exposure to the face and forearms in the middle of the day during summer generates approximately 2,000IU vitamin D.
- Two or three exposures a week are estimated to generate healthy levels during summer.
- Sun exposure for vitamin D production has to be balanced against the risk of skin cancer.
Which vitamin D is synthesised using UVB? What is its precursor?
Vitamin D3
7-dehydrocholesterol
What happens in rickets?
- In children prior to epiphyseal fusion
- Growth retardation
- Expansion of the growth plate
What are the characteristics of osteomalacia?
- Reduce bone strength
- Increase in bone fracture
- Bone pain
- Bending of bones
- Muscle weakness
- Waddling gait
Which lifestyle factors contribute to deficiencies?
Obesity Smoking (and Betel) Alcohol Exercise Exclusive breast feeding after 6-12 months
Which diseases contribute to defiency?
Reduced skin synthesis Decreased bioavailability Drug-related Increased excretion Impaired hydroxylation
Where is vitamin B1 absorbed?
Jejunum
How are water-soluble vitamins generally absorbed and excreted?
- Vitamins hydrolysed in stomach from the protein complexes found in food
- Most of the water-soluble vitamins are absorbed in upper small intestine with exception of vitamin B12, which is absorbed in the ileum
- Water-soluble vitamins are absorbed directly into portal vein and transported to liver to either be stored (B12) or sent into circulation
- Excess water-soluble vitamins are excreted through the kidneys in the urine
What is thiamine pyrophosphate (derived from thiamine aka vitamin B1) involved in?
- Involved in glycolysis and Krebs cycle
- Involved in BCAA metabolism
- Involved in pentose phosphate cycle metabolism
What are the three types of beri-beri and what are their symptoms?
Wet - Cardiac (enlarged heart, tachycardia, high-output CCF, peripheral oedema) - Neurological (peripheral neuritis) Dry - Symmetrical peripheral neuropathy (motor, sensory) Shoshin - Fulminant cardiac failure - Lactic acidosis
What is Wernicke’s encephalopathy and what causes it?
o Horizontal nystagmus (involuntary, rapid and repetitive movement of the eyes)
o Ophthalmoplegia (paralysis or weakness of the eye)
o Cerebellar ataxia (inflamed cerebellum)
- Caused by vitamin B1 (thiamine) deficiency
What is Korsakoff syndrome and what causes it?
o Mental impairment (additional loss of memory and a confabulatory psychosis)
o = The chronic neurologic sequels of Wernicke’s encephalopathy. It is irreversible!
- Caused by B1 (thiamine) deficiency
What is vitamin B3 (niacin) and where is it absorbed and excreted?
- Niacin is a generic name for two chemical forms: Nicotinic acid and nicotinamide.
- Form two pyridine nucleotides (NAD and NADP) which act as hydrogen acceptors in many oxidative reactions and their reduced forms (NADH and NADPH) act as hydrogen donors in reductive reactions.
Absorbed in jejunum
Excreted in urine
Why is B3 (niacin) important and what happens during deficiency?
- Cells use NAD+/NADH as oxidizing or reducing agents
- If the diet is deficient in niacin, cells can manufacture it from tryptophan
- Deficiency states:
o Vegetarian diets (corn based), alcoholism, other vitamin deficiency states
o Hartnup’s disease
Congenital defects of intestinal and kidney absorption of tryptophan
o Carcinoid syndrome
Increased conversion of tryptophan to Serotonin
o Isoniazid use
TB treatment
How is pellagra caused and what are its symptoms?
Caused by B3 (niacin) deficiency Early symptoms: - Loss of appetite - Generalised weakness - Irritability - Abdominal pain - Vomiting - Bright red glossitis Late symptoms: - "Casal's necklace" (skin rash around collarbone) - Vaginitis - Oesophagitis - Diarrhoea - Depression - Seizures - The four D's: dermatitis, diarrhoea, dementia and death
How can B3 (niacin) be toxic at high levels? What are the symptoms of this?
- Flushing has been observed at therapeutic dose of niacin (hypertrigliceridemia)
- Glucose intolerance, macular oedema, and macular cysts
- Fulminant hepatitis have been reported at doses of 3 to 9 g/d.
What is the effect of folate deficiency?
Lack of Folate during neural tube closure has been linked to neural tube defects
- Folic acid is most needed by rapidly dividing cells
How could salt supplementation reduce neural tube defects (NTDs) in Ethiopia?
- If salt supplementation works, it could be game-changing for Ethiopia: A meta-analysis this year concluded that large-scale folic acid food fortification in low- and middle-income countries has lowered the risk of NTDs by 41%. “We have an amazing opportunity to do a lot of good,” says Kenneth Brown, the lead U.S. scientist on the team that met in Addis Ababa.
Why is B12 (cobalimin) unusual? How is it absorbed/excreted?
- B12 is an unusual vitamin in that it is not made by plants but synthesized exclusively by bacteria and archaea
- Absorption:
o Dissociated from proteins in stomach
o Complexes with Intrinsic factor in small intestine
o Absorbed via specific receptors in the terminal ileum - 40% absorbed, 60% excreted in urine or bile
What can B12 deficiency cause?
It is linked to hyperhomovysteinemia, which has itself been associated with increased cardiovascular risk, Alzheimer’s, dementia and osteoporosis
What are some causes of B12 deficiency?
- Inadequate intake: vegans
- Disorders of terminal ileum
- Defective release of cobalamin from food
- Inadequate production of IF
- Transcobalamin II deficiency (rare)
- Congenital enzyme defects (rare)
