The Water-Soluble Vitamins: B Vitamins and Vitamin C

The Water-Soluble The Water-Soluble Vitamins: B Vitamins Vitamins: B Vitamins

and Vitamin Cand Vitamin CChapter 10

StrawberriesStrawberries

Pork!Pork!

Vitamins OverviewVitamins Overview Support nutritional health Vitamins differ from macronutrients

StructureVitamins are individual unlinked molecules

FunctionNo energy yielded, necessary in enzyme rxn’s

Amount neededMeasured in micrograms not grams

Similar to macronutrients- vital to life, organic

Vitamins at WorkVitamins at Work

Vitamins OverviewVitamins Overview

Bioavailability NOT just quantity provided by food Amount absorbed and used by body Factors influencing bioavailability

Efficiency of digestion, transit timeNutrition status, current storesMethod of food preparationSource of nutrient- fortified vs. naturalOther foods consumed at same time


Precursors, aka Provitamins Can be converted to active form in body Ex: beta carotene to Vitamin A

Organic nature Can be destroyed during storage and in cooking

Heat UV Oxygen Soaking / Dilution


Solubility Affects absorption, transport, and excretion Water-soluble vitamins

Move directly into bloodMost travel freely

Fat-soluble vitaminsEnter lymph and then bloodRequire transport proteins


Consumption frequency of B vitamins & C Uptake relative to vitamin stores Toxicity More is not necessarily better Excessive intakes

Risks with levels higher than UL

See “In Summary” for overview section

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More More MoreAs you progress in the direction of more, the effect gets better and better, with no end in sight (real life is seldom, if ever, like this).

As you progress in the direction of more, the effect reaches a maximum and then a plateau, becoming no better with higher doses.

As you progress in the direction of more, the effect reaches an optimum at some intermediate dose and then declines, showing that more is better up to a point and then harmful. That too much can be as harmful as too little represents the situation with most nutrients.

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How it is with VitaminsHow it is with Vitamins

The B Vitamins – As The B Vitamins – As IndividualsIndividuals

Vitamins do not directly provide the body with fuel for energy

Coenzymes Assist enzymes with release of energy

Without coenzyme, an enzyme cannot function

B vitamins form integral part of coenzymesDeficiencies disrupt metabolism

The B Vitamins – As The B Vitamins – As IndividualsIndividuals

Enzyme

Active site

Compounds CD

AB

Active site

Enzyme

Without coenzymes, compounds A, B, and CD don’t respond to their enzymes.

Enzyme

CDA

Enzyme

Vitamin

B

With the coenzymes in place, compounds are attracted to their sites on the enzymes . . .

Coenzyme

Vitamin Coenzyme

Enzyme

Enzyme

. . . and the reactions proceed instantaneously. The coenzymes often donate or accept electrons, atoms, or groups of atoms.

CD

A B

Enzyme

Enzyme

C D

A B

The reactions are completed with either the formation of a new product, AB, or the breaking apart of a compound into two new products, C and D, and the release of energy.

New products

Coenzyme animation 10.2

The B Vitamin Thiamin

Thiamin B1Thiamin B1

Part of coenzyme thiamin pyrophosphate (TPP) Energy metabolism

In conversion of pyruvate to acetyl CoA

TCA cycle conversion of acetyl CoA to succinyl CoA

Nerve activity and muscle activity

Pyruvate reacts with Thiamin di-Pyruvate reacts with Thiamin di-POPO44

Thiamin Thiamin inin TPP TPP

Thiamin B1Thiamin B1 Deficiency- malnourished / alcoholics EtOH impairs absorption, displaces food, causes

urinary loss Beriberi- refined, unenriched rice

Dry – nervous system, muscle weaknessWet – CVS damage, overworked blood vessels

and kidneys retaining salt and water

No toxicity- excess wasted in urine No adverse effects

No UL

Beriberi EdemaBeriberi Edema

Thiamin B1Thiamin B1

Food sources: pork, soy milk, enriched grain foods

Prolonged cooking destroys thiamin Leaches into water when boiling or

blanching foods Cooking methods that conserve thiamin

Steam Microwave

Fig. 10-4, p. 317

The B Vitamin Riboflavin B2The B Vitamin Riboflavin B2

Serves as coenzyme in energy metabolism Flavin mononucleotide (FMN) Flavin adenine dinucleotide (FAD)

Recommendations Deficiency

Inflammation of membranes Toxicity

No UL

Riboflavin part of Coenzyme Riboflavin part of Coenzyme FADFAD

FAD

FADH2 carries the hydrogens to the electron transport chain. At the end of the electron transport chain, the hydrogens are accepted by oxygen, creating water, and FADH2 becomes FAD again. For every FADH2 that passes through the electron transport chain, 2 ATP are generated.

During the TCA cycle, compounds release hydrogens, and the riboflavin coenzyme FAD picks up two of them. As it accepts two hydrogens, FAD becomes FADH2.

FADH2

Riboflavin B2Riboflavin B2

Deficiency- usually accompanies other deficiencies Inflammation of membranes of eyes, mouth, skin,

GI tract No toxicity- excess wasted in urine No adverse effects

No UL

Riboflavin B2Riboflavin B2

Food sources Liver, clams, eggs, mushrooms Milk and milk products Enriched grain foods

Destruction of riboflavin Ultraviolet light Irradiation Not destroyed by cooking

Riboflavin B2 SourcesRiboflavin B2 Sources

The B Vitamin Niacin B3The B Vitamin Niacin B3

Has two chemical structures Nicotinic acid Nicotinamide

Major form of niacin in blood

Two coenzyme forms – metabolic reactions Nicotinamide adenine dinucleotide (NAD)

Carries hydrogens and their electrons NADP (the phosphate form)

Niacin formsNiacin forms

Niacin B3Niacin B3 Recommendations

Body can manufacture from tryptophanOnly occurs after protein synthesis needs

have been met. RDA is stated in niacin equivalents

60 tryptophan make 1 niacin

Deficiency Pellagra

Diarrhea, dermatitis, dementia, death Noted in low-protein, corn-based diet

Pellagra dermatitis– Niacin Pellagra dermatitis– Niacin DeficiencyDeficiency

Niacin B3Niacin B3

Recommendations Adequate intake (AI)

Prescription megadose to lower LDL, raise HDL and adiponectin

Toxicity with some diagnoses No UL for general population Large dose (3-4x RDA) causes “niacin flush”

Niacin B3Niacin B3

Food sources Chicken breast, canned tuna, liver, ground

beef, peanut butter, enriched grain foods Less vulnerable to food preparation losses Mg per serving refer to pre-formed niacin

not equivalents

Niacin B3 SourcesNiacin B3 Sources

BiotinBiotin

The B Vitamin BiotinThe B Vitamin Biotin

Coenzyme that carries activated carbon dioxide Critical in TCA cycle

Delivers carbon to pyruvate to form oxaloacetate

Participates in gluconeogenesis and fatty acid synthesis

Participates in breakdown of fatty acids and amino acids

Biotin and CO2Biotin and CO2

BiotinBiotin

Food sources: liver, egg yolks, soy, fish, also produced by GI tract bacteria

Deficiency: depression, lethargy, numbness in extremities, red, scaly facial rash

No toxicity

Pantothenic AcidPantothenic Acid

Pantothenic Acid in CoAPantothenic Acid in CoA

The B Vitamin Pantothenic The B Vitamin Pantothenic AcidAcid

Deficiency Rare- involves general failure of all body’s

sysems No toxicity No UL Food sources- chicken, beef, potatoes,

oats, tomatoes, liver

B6 (Pyridoxine) B6 (Pyridoxine)

Vitamin BVitamin B66

Three forms Pyridoxal, pyridoxine, and pyridoxamine Conversion to coenzyme PLP


Functions Amino acid metabolism Fatty acid metabolism Urea metabolism Conversion of tryptophan to niacin or serotonin Synthesis of heme, nucleic acids,

neurotransmitters & lecithin

Stored exclusively in muscle tissue


Recommendations Large doses can be beneficial

Deficiency Depression, confusion, convulsions Alcohol destroys B6

Toxicity from 20x UL Irreversible nerve degeneration

Food sources


The B Vitamin FolateThe B Vitamin Folate

FolateFolate Known as folacin or folic acid Primary coenzyme form – THF

(tetrahydrofolate) Transfers single-carbon compounds during

metabolismConvert vitamin B12 to coenzyme form

Synthesizes DNA

Regenerates methionine from homocysteine

Tetrahydrofolate (THF)Tetrahydrofolate (THF)

In foods, folate naturally occurs as polyglutamate. (Folate occurs as monoglutamate in fortified foods and supplements.)

Spinach

Ring structure + Glutamate

Folate In the intestine, digestion breaks glutamates off... and adds a methyl group. Folate is absorbed and delivered to cells.

Intestine

In the cells, folate is trapped in its inactive form.

Cell

To activate folate, vitamin B12 removes and keeps the methyl group, which activates vitamin B12.

Both the folate coenzyme and the vitamin B12 coenzyme are now active and available for DNA synthesis. DNA

FFOOLLAATTEE

FolateFolate Folate disposal

Secretion by liver into bileEnterohepatic circulation from SI to liverVulnerable to GI tract injuries and EtOH abuse Increased need for cell replication

Recommendations Bioavailability of folate

Synthetic form (pills) 1.7x more bioavailable than food sources

Absorbing FolateAbsorbing Folate

Is natural always better?

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FolateFolate

Neural tube defects Supplement use by all women of child-

bearing age for prevention1 month before conceptionThrough first trimester

Folate fortification required in grain products Congenital birth defects- cleft lip and palate

Spina Bifida Neural Tube Defect

Cleft PalateCleft Palate

FolateFolate Heart disease

Role of folate- break down homocysteine, reduce blood clots and atherosclerotic lesions

Risk for heart attacks, stroke, or death from cardiovascular causes?

Cancer Type of cancer Timing of supplementation

Folate and HomocysteineFolate and Homocysteine

FolateFolate Deficiency

Impairs cell division and protein synthesis Red blood cells and GI tract cells falter

Macrocytic anemia GI tract deterioration

Primary deficiencies Secondary deficiencies

Drugs

Folate and DNA / CancerFolate and DNA / Cancer

Folate and DNA / CancerFolate and DNA / Cancer

How “Chemo” worksHow “Chemo” works

FolateFolate Toxicity

Not from food sources Fortified foods or supplements UL has been established 1000 mcg/d

Excess intake of fortified foods canmask a vitamin B12 deficiency

Food sources Heat and oxidation destroy 50% of folate

FolateFolate

B12 CobalaminB12 Cobalamin


Vitamin B12 and folate interdependent for activation Regeneration of methionine, synthesis of

DNA, and synthesis of RNA

Individual roles of vitamin B12 Synthesis of new cells Maintains nerve cells Reform folate enzymes Breaks down some fatty and amino acids

B12 and Folate togetherB12 and Folate together

B12 lost without FolateB12 lost without Folate

B12 Coenzyme FormsB12 Coenzyme Forms


Digestion and absorption Stomach- HCl and pepsin release B12 from

food proteins Small intestine

B12 binds with Intrinsic factor Transported in blood by specific binding

proteins Enters enterohepatic pathway Deficiency is rare except for vegans


Recommendations (RDA) Deficiency caused by

Inadequate absorption Vegan diets Lack of hydrochloric acid or intrinsic factor

Name of deficiency: Pernicious anemia Can be tied to folate deficiency anemia Symptoms- anorexia, sore tongue,

constipation, fatigue, eventual paralysis

Normal blood cells. The size, shape, and color of these red blood cells show that they are normal.

Blood cells in pernicious anemia (megaloblastic). These megaloblastic blood cells are slightly larger than normal red blood cells, and their shapes are irregular.



Toxicity No adverse effects, no UL

Food sources Found exclusively in animal products

Fish, meat, eggs, milk and fortified foods

Destruction by microwaving

Vitamin-Like CompoundsVitamin-Like Compounds Choline

Manufactured from methionine in body Conditionally essential nutrient Adequate intake (AI) not RDA

Common sources- milk, liver, eggs, peanuts Deficiencies are rare Roles in the body

Synthesis of acetylcholine and lecithin Toxicity- sweating, low blood pressure,

reduced growth rate, liver damage

Vitamin Like CompoundsVitamin Like Compounds

Inositol Made from glucose Part of cell membrane structures

Carnitine Transports long-chain fatty acids for oxidation

Both can be made by body No recommendations established

Both are widespread in foods

The B Vitamins in ConcertThe B Vitamins in Concert

Each B vitamin coenzyme is involved in energy metabolism directly or indirectly Facilitate energy-releasing reactions Build new cells to deliver O2 and nutrients (DNA)

Deficiencies B-vitamin deficiency seldom shows up in

isolation Ex: alcohol and drug abuse, polypharmacy

B6, B12, and FolateB6, B12, and Folate

AnemiaAnemia

Is it iron, B12 or folate?

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The B Vitamins In ConcertThe B Vitamins In Concert

A healthy tongue has a rough and somewhat bumpy surface.

In a B vitamin deficiency, the tongue becomes smooth and swollen due to atrophy of the tissue (glossitis).

In a B vitamin deficiency, the corners of the mouth become irritated and inflamed (cheilosis).

The B Vitamins in ConcertThe B Vitamins in Concert

Toxicities possible from oversupplementation Excess eliminated through urine excretion Homeostasis disruption

Food sources first choice Grains- B1, B2, B3, folate Fruits/vegetables- folate Meat group- B1, B3, B6, B12 Milk group- B2, B12

Vitamin CVitamin C

Photomicrograph of Vitamin CPhotomicrograph of Vitamin C

Vitamin C – Roles Vitamin C – Roles

Antioxidant Defends against free radicals

Loses electrons easily Vitamin C recycling Protects tissues from oxidative stress

Disease prevention Enhances iron absorption

Vitamin C as Antioxidant

Vitamin C as Antioxidant

Ascorbic acid protects against oxidative damage by donating its two hydrogens with their electrons to free radicals (molecules with unpaired electrons). In doing so, ascorbic acid becomes dehydroascorbic acid.

Dehydroascorbic acid can readily accept hydrogens to become ascorbic acid. The reversibility of this reaction is key to vitamin C’s role as an antioxidant.

Vitamin C Vitamin C

Vitamin CVitamin C

Cofactor in collagen formation Matrix for bone and tooth formation Conversion of proline to hydroxyproline

Cofactor in other reactions Hydroxylation of carnitine Conversion of tryptophan to serotonin Conversion of tyrosine to norepinephrine Making hormones

Vitamin CVitamin C

In stress Adrenal glands release vitamin C and

hormones into blood Types of stress that increase vitamin C

Prevention and treatment of common cold Conflicting and controversial research Deactivates histamine

Disease prevention

Vitamin C – Vitamin C – Recommendations Recommendations

Prevent overt symptoms of scurvy

Absorption maximum 200 mg

Higher vitamin C levels for smokers

Vitamin C Deficiency Vitamin C Deficiency

Notable signs of deficiency Gums bleed easily around teeth Capillaries under skin break spontaneously

Scurvy Other physical signs Psychological signs Sudden death

Vitamin C – Deficiency Vitamin C – Deficiency

Vitamin C – Toxicity Vitamin C – Toxicity

Supplementation side effects Diarrhea GI distress

UL Interference with medical regimens Medical conditions in which high doses of

vitamin C should not be consumed

Vitamin C Food SourcesVitamin C Food Sources

Fruits and vegetables Potatoes (red potatoes more)

Vulnerable to heat and oxygen Used as antioxidant by food manufacturers

Vitamin C Food SourcesVitamin C Food Sources

Relation between plasma ascorbic Relation between plasma ascorbic acid and mortality in men and women acid and mortality in men and women in EPIC population study: European in EPIC population study: European

Prospective Investigation into Cancer Prospective Investigation into Cancer and Nutrition.and Nutrition.

Lancet. 2001 Mar 3;357(9257):657-63. Khaw KT, Bingham S, Welch A, Luben R,

Wareham N, Oakes S, Day N. Department of Public Health and Primary

Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, UK. [email protected]

Abstract BackgroundAbstract Background Ascorbic acid (vitamin C) might be protective

for several chronic diseases. However, findings from prospective studies that relate ascorbic acid to cardiovascular disease or cancer are not consistent. We aimed to assess the relation between plasma ascorbic acid and subsequent mortality due to all causes, cardiovascular disease, ischaemic heart disease, and cancer.

METHODSMETHODS

We prospectively examined for 4 years the relation between plasma ascorbic acid concentrations and mortality due to all causes, and to cardiovascular disease, ischaemic heart disease, and cancer in 19 496 men and women aged 45-79 years.

METHODSMETHODS

Participants completed a health and lifestyle questionnaire and were examined at a clinic visit. They were followed-up for causes of death for about 4 years. Individuals were divided into sex-specific quintiles of plasma ascorbic acid. We used the Cox proportional hazard model to determine the effect of ascorbic acid and other risk factors on mortality.

FINDINGS FINDINGS

Plasma ascorbic acid concentration was inversely related to mortality from all-causes, and from cardiovascular disease, and ischaemic heart disease in men and women. Risk of mortality in the top ascorbic acid quintile was about half the risk in the lowest quintile (p<0.0001). The relation with mortality was continuous through the whole distribution of ascorbic acid concentrations.

FINDINGS FINDINGS

20 micromol/L rise in plasma ascorbic acid concentration, equivalent to about 50 g per day increase in fruit and vegetable intake, was associated with about a 20% reduction in risk of all-cause mortality (p<0.0001), independent of age, systolic blood pressure, blood cholesterol, cigarette smoking habit, diabetes, and supplement use. Ascorbic acid was inversely related to cancer mortality in men but not women.

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Vitamin and Mineral Supplements

Vitamin and Mineral Vitamin and Mineral SupplementsSupplements

Taken as dietary insurance Costly but harmless practice

Mostly self-prescribed Physician recommendation increasing Improving food choices is preferred course

of action

Arguments for SupplementsArguments for Supplements

Correct overt deficiencies Therapeutic doses prescribed by physician

Acting as drug

Support increased nutrient needs Certain stages of life

Improve nutrition status Improve body defenses Reduce disease risks

Who Needs Supplements?Who Needs Supplements?

Specific nutrient deficiencies

Low energy intakes Vegans and older

adults with atrophic gastritis

Lactose intolerance GI diseases Certain medications

Certain stages of life cycle

Inadequate milk intake, sun exposure, or dark skin

Medical conditions that interfere with nutrients in body

Arguments Against Arguments Against SupplementsSupplements

Toxicity Supplement users are more likely to have

excessive intakes Issues with children

Life-threatening misinformation No guarantee of supplement effectiveness

Unknown needs “Ideal” supplements

Arguments Against Arguments Against SupplementsSupplements

False sense of security Other invalid reasons

Today’s health problemsOvernutritionPoor lifestyle choices

Bioavailability and antagonistic actions Nutrients may interfere with one another’s

actionMake dietary modifications first

Selection of SupplementsSelection of Supplements

Follow directions carefully Single, balanced vitamin-mineral

supplement U.S. Pharmacopeia (USP) logo

Logo assurances Two basic questions

Form Contents

Misleading ClaimsMisleading Claims

Organic or natural vitamins High potency claims Marketing strategy

“New” vitamins “Green” pills Stress relief

Internet advertising Cost

Regulation of Regulation of SupplementsSupplements

Food and Drug Administration (FDA) Dietary Supplement Health and Education

Act of 1994 Enable consumers to make informed choices Same general labeling requirements as

foods Net effect: deregulation of supplement

industry

Documents

The Water-Soluble Vitamins: B Vitamins and Vitamin C