The Water Soluble Vitamins & Trace elements

Dr.Parvathy

Dept. of Pathology

B Complex Primary Functions

Energy metabolismThiamin (B-1), Riboflavin (B-2), Niacin (B-

3), Pyridoxine (B-6), Biotin, Pantothenic Acid

Red blood cell synthesisFolate, B12

Homocysteine metabolismFolate, B12, B6

Enrichment Act of 1941 and 1998

Many nutrients lost through milling process of grains

Grain/cereal products are enriched

Thiamin, riboflavin, niacin, folate, iron

Whole grains contain original nutrients

Enriched grains still deficient in B-6, magnesium and zinc

Thiamin (B1)

Thiamine Functions:Synthesis of ATPCo-factor in pentose phosphate

pathwayMaintains neural membranes and

conduction

Deficiency of ThiaminOccurs where polished rice is the only staple

Chronic alcoholics

Little stored in body, so alcoholic binge of 1-2 weeks may result in deficiency

Pernicious vomiting or diarrhea• Wernicke-Korsikof f Syndrome

– Wernicke encephalopathy• Korsakoff’s psychosis• Result of thiamine deficiency caused by alcoholism

Beriberi (I can’t I can’t)Weakness, nerve degeneration, irritability,

poor arm/leg coordination, loss of nerve transmission

Edema, enlarged heart, heart failureSymptoms due to poor metabolism of

glucoseDepression and weakness can be seen after

only 10 days on a thiamin-free diet

Wet and Dry BeriBeri

Food Sources of ThiaminGreen beans, milk, orange juice, organ meats, peanuts, dried beans and seed

Enriched breads and grains/ whole grains

Thiaminase found in

raw fish Destroys thiamin

RDA For Thiamin

1.1 mg/day for women1.2 mg/day for menSurplus is rapidly lost in urine; non toxic; no Upper Level

Riboflavin (B2)

Riboflavin is a critical component of flavin mononucleotide (FMN) & flavin dinucleotide (FAD) which participate in redox reactions

Ariboflavinosis

Food Sources of Riboflavin

Milk/productsEnriched grainsReady to eat cerealsLiverVegetables (asparagus,

broccoli, greens)Sensitive to uv radiation

(sunlight)Stored in paper, opaque plastic containers

RDA for Riboflavin

1.1 mg/day for women

1.3 mg/day for men

Average intake is above RDA

Toxicity not documented

No upper level

Niacin (B3)

Nicotinic acid and nicotinamide

Essential component of NAD & NADP which play central roles in cellular intermediate metabolism. Synthetic pathways require niacin, especially fatty acid synthesis

Deficiency of Niacin: Pellagra3 Ds

Dermatitis - which most often occurs in sun exposed areas of face and upper extremity

Dementia - results from neuronal degeneration in the brain and spinal column

Diarrhea - is associated with edema and inflammation of the intestinal submucosa.Poor appetite, weight loss, weakness

Pellagra

Food Sources of NiacinEnriched grains, ready to eat cerealsBeef, chicken, turkey, fish peanutsHeat stable; little cooking

loss

RDA for Niacin14 (mg) NE/day for women

16 (mg) NE/day for men

Upper Level is 35 mg

Other names

Nicotinic acid, Nicotinamide, Niacinamide,Vitamin B3

Precursor: dietary tryptophan(60mg=1mg)

Toxicity S/S: headache, itching, flushing, liver and GI damage

Pantothenic Acid/ Vit B5

Part of Coenzyme-AEssential for metabolism of CHO, fat, protein

Deficiency rareNo known toxicity

Food Sources of Pantothenic acid

“From every side”

Meat

Milk

Mushroom

Liver

Peanut

Eggs

Adequate Intake= 5 mg/day

Daily Value 10 mg

Average intake meets AI

Biotin

Free and bound form

Metabolism of CHO and fat

Assists the addition of CO2 to other compounds

Synthesis of glucose, fatty acids, DNA

Help break down certain amino acids

Biotin DeficiencyRaw egg whites avidin bind biotin → deficiencyRequires large amountScaly inflamed skin, tongue, and lip changesPoor appetite, nausea, vomitingAnemiaMuscle pain and weaknessPoor growth

Food Sources of Biotin

Cauliflower, yolk, liver,

peanuts, cheese

Intestinal synthesis of

biotin

Biotin Needs

Adequate Intake is 30 ug/day for adults

Deficiency rare

No Upper Level for biotin

Relatively nontoxic

Pyridoxine (B6)

Coenzyme

Activate enzymes needed for metabolism of CHO, fat , protein

Synthesize nonessential amino acid via transamination

Synthesize neurotransmitters

Synthesize hemoglobin and WBC

Pyridoxine/B6 Deficiency

Widespread symptoms• Depression• Vomiting• Scaly dermatitis• Nerve irritation• Impaired immune system

Food Sources of Vitamin B-6

Well absorbed• Meat, fish, poultry• Enriched cereals• Potatoes• MilkLess well absorbed• Fruits and vegetables: Banana, spinachHeat and alkaline sensitive

B6 Toxicity

Nerve damage

Difficulty walkingNumbness in hands/feetCan lead to irreversible nerve damage with > 200 mg/dayUpper Level set at 100 mg/day

RDA for Vitamin B-6

1.3 mg/day for adults

1.7 mg/day for men over 50

1.5 mg/day for women over 50

Average intake is more than the RDA

Athletes may need more

Alcohol destroys vitamin B6

Folate

Part of coenzymes THF (tetrahydrofolate) and DHF (dihydrofolate) used in DNA synthesis and therefore important in new cell formation-Anticancer drug methotrexate

Homocysteine metabolismNeurotransmitter formation

Deficiency of Folate

Similar signs and symptoms of vitamin B-12 deficiency

Anemia

Pregnant women

Alcoholics

Megaloblastic Anemia

Neural Tube Defects

Food Sources of FolateLiver

Fortified breakfast cereals

Grains, legumes

Foliage vegetables

Susceptible to heat,

oxidation, ultraviolet light

Synthetic form better

absorbed

RDA for Folate

400 ug/day for adults

(600 ug/day for pregnant women)

Excess can mask vitamin B-12 deficiency

Upper Level set at 1 mg

Cobalamin/Vitamin B-12

Synthesized by bacteria, fungi, and other lower organisms

Role in folate metabolism

Maintenance of the myelin sheaths

RBC formation

Part of coenzymes methylcobalamin and deoxyadenosylcobalamin used in new cell synthesis

Absorption requires

HCl

Pepsin

Intrinsic factorDifficult for vegetarians to obtainPernicious anemia

Nerve degeneration, weakness Tingling/numbness in the extremities (parasthesia) Paralysis and death Looks like folate deficiency

Usually (95%) due to decreased absorption ability

Vitamin B12 deficiency

Diagnosis: Schilling test

Treatment: 1000mg Vitamin B12 IM daily for two weeks and monthly injections for life

High Risk: African Americans, northern Europeans, elderly

Food Sources of Vitamin B-12

Synthesized by bacteria, fungi and algae

Animal products, meat

Seafood

Eggs

Milk

RDA for Vitamin B-12

2.4 ug/ day for adults and elderly adults

B-12 stored in the liver

Non-toxic (no Upper Level)

Vitamin C

Synthesized by most animals (not by humans)Decrease absorption with high intakesExcess excreted

Functions of Vitamin C

Reducing agent (antioxidant)Iron absorption (enhances)Synthesis of collagenImmune functionsWound healing

Antioxidant

Can donate and accept hydrogen atoms readilyWater-solubleNeeds are higher for smokersMay prevent certain cancers (esophageal, oral, stomach cancer, cardiovascular disease, cataracts)

Vitamin C Deficiency: History of Scurvy

Sailors on long sea voyages suffered horribly from scurvyOn Vasco da Gama's voyage to the East Indies in 1497, 100 out of 160 men were lost from the disease.

Scurvy in the British Royal Navy

James Lind published his Treatise on the Scurvy in 1754. Lime juice was made mandatory on British Navy sailing ships 40 years later

Deficiency of Vitamin CScurvyDeficient diet for 20-40 days Fatigue, pinpoint hemorrhagesBleeding gums and joints. HemorrhagesAssociated with poverty; macrobiotic diet

Rebound ScurvySudden halt to high levels of vitamin C

supplements

ScurvyScorbutic Rosary

Follicular Hemorrhages

Food Sources of Vitamin C

Citrus fruit

Potato

Green pepper

Cauliflower

Broccoli

Strawberry

Spinach

Easily lost through cooking

Sensitive to heat

RDA for Vitamin C

90 mg/day for male adults

75 mg/day for female adults

+35 mg/day for smokers

Upper Level is 2 g/day

Vitamin C Excess

Hemochromatosis

Oxalate kidney stones

Erodes tooth enamel

Choline

Newest essential nutrient

Grouped with B group vitamins

All tissues contain choline

Precursor for acetylcholine (neurotransmitter)and phospholipids

Some role in homocysteine metabolism

Food Sources of Choline

Widely distributed

Milk

Liver

Eggs

Peanuts

Lecithin added to food

Deficiency rare

Trace Elements

Essential Trace Elements:

iron, zinc, copper, cobalt, chromium, fluorine, iodine, manganese,

molybdenum and selenium

Probably essential:

nickel, tin, vanadium, silicon, boron

Copper

Metabolism• Copper circulates bound to

ceruloplasmin

• Excretion occurs via transport of copper into bile and elimination in feces

cofactor for many cuproenzymes including:cofactor for many cuproenzymes including:

•Cu, Zn-superoxide dismutase (antioxidant)Cu, Zn-superoxide dismutase (antioxidant)•Cytochrome C oxidase (ATP synthesis, neurologic Cytochrome C oxidase (ATP synthesis, neurologic function)function)•Ceruloplasmin (6 atoms per molecule)Ceruloplasmin (6 atoms per molecule)•Lysyl oxidase (cross links and stabilizes connective Lysyl oxidase (cross links and stabilizes connective tissue proteins)tissue proteins)•Tyrosinase (melanin synthesis)Tyrosinase (melanin synthesis)

Copper Physiology/DeficiencyCopper Physiology/Deficiency• Acquired deficiency is rareAcquired deficiency is rare

• Manifestations:Manifestations: Hypochromic microcytic anemiaHypochromic microcytic anemia NeutropeniaNeutropenia Hypopigmentation of hair and skinHypopigmentation of hair and skin Structural abnormalities in connective tissueStructural abnormalities in connective tissue Fetal and neonatal deprivation leads to Fetal and neonatal deprivation leads to

neurologic dysfunctionneurologic dysfunction Reduced levels of circulating copper and Reduced levels of circulating copper and

ceruloplasminceruloplasmin

Food Sources

organ meats, seafood, nuts, seeds, cereals, whole grains, cocoa

Inborn Errors of Copper Metabolism:Inborn Errors of Copper Metabolism:

Wilson’s Disease (Hepatolenticular Wilson’s Disease (Hepatolenticular Degeneration)Degeneration)

Menkes Kinky Hair SyndromeMenkes Kinky Hair Syndrome

Pili torti (Menkes Disease)

Iodine

-body normally has 20-30 mg of iodine and more than 75% is in the thyroid gland

-the rest is in the mammary gland, gastric mucosa, and blood

-it’s only function is related to thyroid hormone

Food Sources

foods of marine origin (seaweed), processed foods, iodized salt

Deficiency-goiter—enlargement of the thyroid gland goitrogens -cabbage, turnips, peanuts, soybeans

-deficiency may be absolute—in areas of deficiency, or relative—adolescence, pregnancy, lactation

-goiters are more prevalent in women and with increased age

Endemic Cretinism

severe deficiency during gestation and early postnatal growth: cretinism

(mental deficiency, spastic diplegia, quadriplegia, deaf mutism, dysarthria, shuffling gait, short stature, hypothyroidism)

Iodine deficiency is the most Iodine deficiency is the most common nutrient deficiency common nutrient deficiency

in the world!in the world!

Iodine Excess and ToxicityIodine Excess and Toxicity

Humans are remarkably tolerant to high iodine intakes

In iodine deficiency, repletion must be done slowly to prevent hyperthyroidism

Goiter

Endemic to parts of

S. America and India

Sporadic cases in U.S.

Selenium deficiency

(needed to convert T4 to T3)

Goiter - Complications

Usually asymptomaticAcute pain from thyroidal hemorrhageDysphagia Dyspnea

ChromiumRegulation of glucose metabolism as a component of glucose tolerance factor (GTF).GTF increases effect of insulin (by facilitating its binding to cell receptor site).Chromium regulates plasma lipoprotein concentration.

Reduces serum cholesterol and serum triglycerides. Both chromium and Fe are carried by Tf, however albumin can also assume this role

Food Sources

bread, meats, poultry, fish, beer

Deficiencyaltered CHO metabolism, impaired glucose tolerance, glycosuria, fasting hyperglycemia, increased insulin levels and decreased insulin binding to receptors-impaired growth, peripheral neuropathy, negative nitrogen balance

Toxicitychronic renal failure

Cobalt

-most stored with vitamin B12

-component of B12—cobalamin

-essential for maturation of RBC’s and normal function of all cells

Deficiency

-**macrocytic anemia

Toxicitypolycythemia

-hyperplasia of BM

-reticulocytosis

-increased blood volume

Selenium-glutathione peroxidase

• --overlaps with vit E for antioxidant effects• Iodothyronine 5’- deiodinase

• Thioredoxin reductase

• Epidemiologic evidence indicates low intakes of Se are associated with higher risk of prostate cancer

Food SourcesFood Sources

Food content tends to follow Se content of soil – richest food sources are organ meats and sea foods, followed by cereals and grains, dairy products, fruits and vegetables

• Requirements determined based on serum glutathione peroxidase activity

Selenium Deficiency DiseasesSelenium Deficiency Diseases

•Human deficiency is rare except in areas with low Se content in soil

Keshan disease occurs in Keshan China: endemic cardiomyopathy and muscle weakness (due to oxidized lipids)

Aggressive supplementation has eliminated disease

•Iatrogenic deficiency TPN without supplemental Se

Selenium Toxicity

Acute-cardiorespiratory collapse (gram amounts)

Chronic (selenosis) -changes in nail structure and loss of hair (intakes ~6x UL)

Molybdenum

-relationship with copper and sulfate-cofactor of many enzymes involved in the catabolism of sulfur AA, purines and pyridines-Toxicity: gout-like syndrome, reproductive SE’s-Deficiency: increased risk with co-existing copper deficiency, TPN

Manganese •High concentration of Mn2+ is present in mitochondria• Functions as a necessary factor for activation of glycosyltransferases (enzymes responsible for the synthesis of oligosaccharides, glycoproteins, proteoglycans.• Required for superoxid dismutase activity, for activity of metalloenzymes:

hydrolaseskinasesdecarboxylasestransferases.

Deficiency of Mn extensively reduce glycoprotein and proteoglycan formation.

Iron Adult human body contains 3-4 Gm 60-70% is present in Blood and rest in storage

form. Each Gm of Hb contains 3.34mg of Iron.

Requirement : 1 mg per day for Male 2.5 mg for Females 3.5 mg for Females in Physiological stress

conditions

Sources of iron Haem Iron:

Liver, meat, poultry, Fish

Non Haem Iron: Cereals, GLV, Legumes,, Nuts, Oil seeds,

Dried Fruits, Jaggery

Factors interfere in absorption are enzymes in the food – Phytates, Oxalates, Phosphates, Dietary fibres

Ascorbic acid is the most potent enhancer iron

Iron Deficiency Occurs in 3 stages: First Stage: Decreased storage without any

other detectable abnormalities Second Stage: stores are exhausted, serum

Ferritin level decreases. Third Stage: Decrease in Hemoglobin

percentage

Functional disturbances: decrease in resistance to infection, increase morbidity & mortality, decreased work performances, impaired cell mediated immunity

Evaluation of iron status

1. Hemoglobin Concentration: relative index of iron deficiency. ( early Anemia if Hb is 10-11g% & marked anemia Hb is < 10g%).

2. Serum Iron concentration: useful index ( Normal 0.8 to 1.8mg /L)

3. Serum Ferritin level: Gold standard & sensitive tool for evaluation and reflects the size of the iron status ( < 10Micrgms/L)

4. Serum Transferrin Saturation: 16% - 30%

Correction of Iron Deficiency

Oral iron supplements 100-200 mg elemental iron daily Higher doses are of no benefit Ferrous sulphate 65mg/tab Pregnant women- 100mg/tablet

(+ folic acid)

Fluorine It is found in combined forms 96% of fluorides in the body found in bone and

teeth. An essential for normal mineralisation of bones

and formation of dental enamel

Source: Drinking water : Fluorine in the drinking water is

0.5 mg per ltr. Excess of fl > 3mg causes flourosis.

Foods: Sea fish, cheese, Tea It is a two edged sword ( deficiency or excess)

Zinc Adult body contains 1.4 to 2.3 gms of Zinc Plasma level- 96Microgm per 100 ml ( adults), 89

Microgram per 100 ml (children)

Functions are Active role in metabolism of glucose and proteins Synthesis of insulin by pancreas Immunity functions

Food sources : meat, milk, fish Plant sources have low bioavailability

Zinc deficiency 1. Growth failure2. Sexual infantilism in adolescents, loss of taste,

delayed wound healing, decrease in immunosynthesis.

3. Spontaneous abortions, stillbirths, congenital malformations, anencephaly

4. LBW, Intra Uterine deaths, premature labour.

5. Requirement is 15mg for men6. 12 mg for women, 10mg for children