MMSC 407 - Vitamins

How are vitamins identified?

By letter, number to indicate dif forms

Fat-soluble vs. Water-soluble vitamins

Fat-soluble vitamins remain in system for longer, whereas water-soluble vitamins are shed in urine within 24 hours

Fat-Soluble vitamins

A, D, E, K

Dietary sources of Vitamin A

leafy green vegetables, orange/yellow vegetables, tomatoes, red bell pepper, cantaloupe, mango, beef liver, fish oils

Symptoms of vitamin A deficiency

Dry skin, dry eyes, night blindness, infertility, delayed growth (in children), poor wound healing, acne

In developing nations, where vit A deficiency is more severe (malnutrition), responsible for upper/lower respiratory infections

What is hypervitaminosis A?

Results from taking high-dose supplements over long periods of time - Vit A is a fat soluble vitamin so it is stored in the liver and can lead to toxicity and sxs (vision changes, bone swelling, mouth ulcers, confusion)

What vitamin should pregnant women avoid taking too much of?

Vitamin A

Recommended daily allowance (RDA) of vitamin A

Given as retinol activity equivalents to account for different bioactivities of retinol and provitamin A carotenoids (converted to retinol)

-14-51+: 900 (males) and 700 (females)

-14-18: 750mcg (pregnancy) and 1200 (lactation)

-19-50: 770mcg (pregnancy) and 1300 (lactation)

Vitamin A reference range

15 - 60 ug/dL

Chemistry of vitamin A

retinols, beta-carotene

Chemistry of Vitamin E

alpha-tocopherol is the only form of vit E used by the human body (easily absorbed into skin)

Main role of alpha-tocopherol (vit E)

Act as an antioxidant, scavenging free radicals that can damage cells

Dietary sources of Vitamin E

Best natural sources of vit E: Vegetable oils (wheat germ, sunflower, and safflower oils are the best source of vit E), Nuts (esp. Almonds), seeds

Provide some vit E: Green vegetables, added to breakfast cereals, fruit juices, margarines

Causes of vitamin E deficiency

Rare in healthy people; Commonly linked to certain diseases in which fat is not properly digested or absorbed (Crohn's disease, cystic fibrosis, AVED) - Vit E needs some fat for the digestive system to absorb it

Symptoms of vitamin E deficiency

Nerve and muscle damage, loss of body movement control, muscle weakness, vision problems, weakened immune system

Vitamin E toxicity

Relatively large amounts of vit E are usually not harmful, but may cause muscle weakness, fatigue, nausea, and diarrhea. The most significant risk is bleeding (doses of >1000 mg/day)

Reference range of vitamin E

Adult: 5.5-17ug/mL
Children: 3-18.4 ug/mL

Two forms of vitamin K

Phylloquinone (green leafy vegetables)
Menaquinones (some animal foods and fermented foods; also produced by bacteria in the body)

Major role of Vitamin K

Key role in coagulation (prevents excessive bleeding)
Also has roles in bone development and cardiovascular health

Vitamin K toxicity

Vit K toxicity is extremely rare; Only reported toxicity comes from menadione (nutritional supplement in animal feed - humans should not be consuming this). Sxs of vit K toxicity include jaundice, hyperbilirubinemia, hemolytic anemia, and kernicterus in infants

Vitamin K deficiency leads to...

Significant bleeding, poor bone development, osteoporosis, cardiovascular disease

Vitamin K reference range

0.2-3.2 ng/mL - BUT impaired blood clotting has been associated with levels below 0.5 ng/mL

Common name of vitamin B1

Thiamine

How does thiamine enter the body?

Thiamine is absorbed in the blood from the GI tract
_________________

Chemistry of Vit B1

Pyrophosphate groups

Dietary sources of vitamin B1

Fortified breakfast cereals, pork, fish, beans/lentils, green peas, enriched cereals/breads/noodles/rice, sunflower seeds, yogurt

Role of vitamin B1

Helps the body's cells change carbohydrates into energy; Role in muscle contraction and conduction of nerve signals

RDA for thiamine (vit B1)

RDA thiamine for men over 19: 1.2 mg daily
RDA thiamine for women over 19: 1.1 mg daily
Pregnant and lactating women: 1.4 mg daily

Symptoms of thiamine deficiency

Early (vague) symptoms - Fatigue, irritability, poor memory, loss of appetite, sleep disturbances, abdominal discomfort, weight loss

Severe thiamine deficiency (beri-beri) - Nerve, heart, and brain abnormalities. Wet beri-beri: cardiovascular sxs; Dry beri-beri: Nervous system sxs

Vitamin B1 toxicity

Unlikely to reach a toxic level of B1 from food alone (because it is water-soluble). The body will absorb less of the nutrient and flush out any excess through urine

No levels of thiamine have been established for toxicity

Laboratory assessment of vitamin B1

No toxicity established, so this is not done often

The biologically active form of B1 (thiamine pyrophosphate) is best measured in whole blood (EDTA). Reflects intake

** The test offered by LabCorp has not yet been cleared or approved by the FDA

Common name vitamin B2

Riboflavin

Role of riboflavin

Helps to maintain normal levels of homocysteine

What does riboflavin look like when exposed to UV light?

Riboflavin will turn yellow, naturally fluorescent

Exposure to UV light inactivates riboflavin - Lengthy light therapy to treat jaundice in newborns or skin disorders can lead to riboflavin deficiency

Sources of vitamin b2

90% of dietary riboflavin is in the form of FAD or FMN

Where is riboflavin absorbed and stored?

Absorbed in proximal small intestine

Stored in liver, hearts, and kidneys (excess excreted in urine)

Where is riboflavin produced in the body?

Bacteria in the large intestine produce riboflavin ______________-

Dietary sources of Vit B2

Eggs, organ meats (kidney/liver), lean meats, milk, some vegetables, grains and cereals are fortified with riboflavin

In most foods is in the form of FAD (although the main form in eggs and milk is free riboflavin)

What is a stable and sensitive measure of riboflavin deficiency?

Erythrocyte glutathione reductase activity coefficient (EGRAC) - Based on ratio between this enzymes in vitro activity in the presence of FAD to that without added FAD

What value of EGRAC indicates adequate riboflavin status?

< 1.2 is adequate
1.2-1.4 is marginal deficiency
>1.4 indicates riboflavin deficiency

Fluorometric measurement of urinary excretion to measure riboflavin

Fluorometric measurement of urinary excretion over 24 hours (total amount of riboflavin excreted) - Typically reflects dietary intake

Healthy adult riboflavin secretion ____________--

RDA riboflavin

Not very different for males and females until older age (1.3 mg males; 1.1 mg females); Increases with age; More required during pregnancy

For babies, we cannot overload with B2

Function of vitamin B6

Coenzyme in more than 100 reactions; Mostly concerned with protein metabolism

PLP and PMP are involved in amino acid metabolism

PLP is involved in __________

-Structure Identifier: “N” in the ring structure

Average vit B6 intake

Men: 2 mg/day

Women: 1.5 mg/day

Dietary sources of vit B6

Chickpeas, tuna, salmon, potatoes, turkey, bananas, fortified cereals, many more!

With B6 provided in supplements, intake is often not enough to reach the appropriate level

What affects your ability to uptake vit B6?

Smoking (first or second hand); levels are lower in women than men, in underweight people, and in black than white

Vitamin B6 Deficiency

Uncommon; Usually associated with deficiencies in other B vitamins; Causes biochemical changes that become more obvious as deficiency progresses

Symptoms of severe vit B6 deficiency

Microcytic anemia, dermatitis with scaling on lips and cracks at corners of mouth, glossitis (swollen tongue), depression and confusion; weakened immune system

Infants (mod deficiency): Irritability, abnormally acute hearing, convulsive seizures

Causes of vit B6 deficiency

End-stage renal disease; kidney diseases; malabsorption syndromes

Common name for vit B12

Cyanocobalamin (Co+ in center of molecule - important)

"Cobalamins"

Why is B12 important?

Vit B12 is required for the development, myelination, and function of the CNS; healthy RBC formation; DNA synthesis

Cofactor for two enzymes (methionine synthase, L-methylmalonyl-CoA mutase)

RDAS for vit B12

Not many differences between genders; (2.4 mcg for men & women) Higher during pregnancy and lactation (2.6 for pregnant & 2.8 lactating)

Cannot give too much to infants

Dietary sources of vit B12

Beef liver (71% wow!), clams, nutritional yeast, salmon, tuna, milk, yogurt

Causes of vit B12 deficiency

Difficulty absorbing B12 from food, lack of intrinsic factor (pernicious anemia), GI surgery, prolonged use of certain medications

Clinical Manifestations of Vit B12 deficiency

Megaloblastic anemia (large, nucleated RBCs), low counts of WBCs/PLTs, glossitis, fatigue, palpitations, pale skin, dementia, weight loss, infertility

Pregnant women: Neural tube defects

RDA vitamin C for healthy adult nonsmokers (male vs female) and children

Males: 105.2 mg/day
Females: 83.6 mg/day
Reference Range: 0.6-2mgdL mg/day

What does vitamin C deficiency cause?

Scurvy
As vit C levels drop, collagen synthesis slows, connective tissues become weak causing petechiae, ecchymoses, purpura, joint pain. As scurvy worsens, you will eventually see depression and swollen, bleeding gums or loss of teeth. Increased bleeding may lead to iron deficiency anemia

Fatal if untreated

Groups at risk of vitamin C inadequacy

Smokers / subject to secondhand smoke
Infants fed with evaporated or boiled milk

Tolerable upper intake levels of vitamin C for adults

2000 mg

Name for vitamin B7

Biotin (vitamin H)

Major role of biotin

Cofactor for five carboxylases (catalyze steps in metabolism of fatty acids, glucose, and amino acids

Role in histone modifications, gene regulation, and cell signaling

RDAs vitamin B7 (healthy adults)

30mcg

Dietary sources of biotin

Beef liver, egg, salmon, pork chop, hamburger, sunflower seeds, sweet potato, almonds

What do high levels of biotin interfere with?

High intake of biotin (hair/skin/nail vitamins) may interfere with diagnostics assays that measure thyroid hormones or troponin tests to diagnose congestive heart failure (falsely normal or abnormal results)

Name for vitamin B9

Folic acid

Vit B9 molecule

Very large; Variable R groups

Which form of vitamin B9 is absorbed better than from food sources and why?

Folate - Helps form DNA and RNA and is involved in protein metabolism. Folate is also needed to produce healthy RBCs and is critical during periods of rapid growth (pregnancy and fetal development)

Dietary sources of folic acid

Dark green leafy vegetables, beans, peanuts, sunflower seeds, fresh fruits, whole grains, liver, aquatic foods, eggs

Effect of alcoholism on folic acid

Alcoholism interferes with the absorption of folate and speeds the rate that folate breaks down and is excreted from the body

Effect of intestinal surgeries or digestive disorders that cause malabsorption

Anything that causes intestinal malabsorption will give problems with maintaining folate levels (celiac disease, inflammatory bowel disease)

Effect of mutated MTHFR gene

With a mutated MTHFR gene, people cannot convert folate to its active form to be used by the body

RDA Folic Acid

mg of DFE (Dietary folate equivalents)

Adults: 400 mg DFE
Pregnant women: 600 mg DFE
Lactating women: 500 mg DFE

People who drink alcohol should aim for at least 600 mg DFE of folate daily since alcohol can impair its absorption

Name for vitamin B3

Niacin (nicotinic acid)

Function of niacin

All tissues (except skeletal muscle) in the body convert absorbed niacin into its main metabolically active form, coenzyme NAD. Many enzymes require NAD to catalyze reactions in the body. NAD is also converted into NADP

-More than 400 enzymes require NAD to catalyze reactions in the body,

What is the most sensitive and reliable measure of niacin status?

24 HOUR URINE
Urinary excretion of N1-methyl-nicotinamide and N1-methyl-2-pyridone-5-carboxamide

RDA niacin (adults)

Males: 16 mg NE
Females: 14 mg NE
Pregnant women: 18 mg NE
*Levels are same for male and female until puberty

Dietary sources of niacin

Beef liver, chicken breast, marinara sauce, turkey breast, salmon, tuna, pork tenderloin, ground beef, brown rice, peanuts, fortified breakfast cereals

Effects of niacin deficiency

Pellagra - Pigmented rash or brown discoloration on skin exposed to sunlight; The skin also develops a roughened, sunburned-like appearance; Bright red tongue and changes in the digestive tract leading to vomiting, constipation, or diarrhea

Neurological symptoms: Depression, apathy, loss of memory, aggression, paranoia, suicidal behaviors, auditory/visual hallucinations

Name for vitamin B5

Pantothenic Acid

Main function of pantothenic acid

Synthesis of coA (coA is essential for fatty acid synthesis and degradation) and acyl carrier protein (fatty acid synthesis)

What is the most reliable indicator of pantothenic acid? Normal values?

Urinary concentrations are reliable because they relate to dietary intake. With a typical American diet, the urinary excretion rate for pantothenic acid is 2.6 mg/day

-less than 1mg/day suggest deficiencies

RDA pantothenic acid

5 mg healthy adults
Pregnancy: 6 mg

Dietary sources of pantothenic acid

Beef liver, fortified breakfast cereals, shitake mushrooms, sunflower seeds, chicken breast, avocados, milk, potatoes, egg, greek yogurt

Proposed effect of vitamin B5 on hyperlipidemia

Because of B5's role in triglyceride synthesis and lipoprotein metabolism, experts have hypothesized that pantothenic acid supplementation might reduce lipid levels in patients with hyperlipidemia

Units of measurement for trace elements

ug/dL or mg/kg

What enzyme is required for transport and storage of reactive metal ions?

Metalloproteinase

Causes of deficiency of trace elements

Lack of absorption
Liver/bowel/renal disease
Catabolic responses to injury, infection, and disease

Innate trace element diseases we will test for in a newborn

Iron, copper, zinc, molybdenum, selenium, iodine

Where is chromium found in blood?

Bound to plasma protein - transferrin
Accumulates in liver, spleen, soft tissue, and bone

What is the best test method for chromium?

Urinalysis (per 24 hours)
Levels are related to recent chromium intake, NOT good indicators of chromium body stores
Cr levels can also be found in hair/nails

Adequate intakes (AIs) for chromium for adults

Males: 35 mcg
Females: 25 mcg
More during pregnancy and lactation

Dietary sources of chromium

Grape juice, ham, english muffin, brewer's yeast, orange juice

Role of chromium in metabolic syndrome

Studies have shown that if we give chromium supplements to patients with metabolic syndrome, they have shown benefits

Where do we get cobalt?

Cobalt must be supplied by diet

Which vitamin is cobalt a component of?

Vitamin B12

Major roles of cobalt

Cobalt is very important for forming amino acids and some proteins to create myelin sheath in nerve cells

Industrial exposure to cobalt

Cobalt is not highly toxic, but high doses will produce adverse clinical manifestations

Symptoms of high dose cobalt exposure

Contact dermatitis, respiratory sensitization, asthma, shortness of breath, decreased pulmonary function

Blood reference range for cobalt

< 10 nmol/L
(higher suggests environmental exposure or joint replacement)

Dietary sources of cobalt

Fish, nuts, green leafy vegetables, cereals (oats)