Essential Vitamins for Clinical Practice: RDAs, Toxicity, Sources & Deficiency

Vitamin C RDA for Men

90 mcg

Vitamin C RDA for Women

75 mcg

Vitamin C RDA for Pregnancy

100 mg

Vitamin C RDA for Lactation

120 mg

Vitamin C extra intake for smokers

Extra 35 mg/d

Folate RDA for Adults 19+

400 mcg DFE

Folate RDA for Pregnancy

600 mcg DFE

Folate RDA for Lactation

500 mcg DFE

1 DFE definition

1 mcg food folate, 0.6 mcg folic acid from supplement or fortified food, 0.5 mcg folic acid from supplement on empty stomach

Thiamin RDA for Men

1.2 mg/d

Thiamin RDA for Women

1.1 mg/d

Thiamin RDA for Pregnancy

1.4 mg/d

Thiamin RDA for Lactation

1.5 mg/d

Vitamin B6 RDA for Adults 19-50

1.3 mg/d

Vitamin B6 RDA for Pregnancy

1.9 mg/d

Vitamin B6 RDA for Lactation

2 mg/day

Vitamin B6 RDA for Age 51+ Women

1.5 mg/d

Vitamin B6 RDA for Age 51+ Men

1.7 mg/d

Vitamin B12 RDA for Age 14+

2.4 mcg/d

Vitamin B12 RDA for Pregnancy

2.6 mcg/d

Vitamin B12 RDA for Lactation

2.8 mcg/d

Riboflavin RDA for Men

1.3 mg/d

Riboflavin RDA for Women

1.1 mg/d

Niacin RDA for Men

16 mg/d

Niacin RDA for Women

14 mg/d

Biotin AI

30 mcg/d, deficiency is rare

Pantothenic Acid AI for Adults

5 mg/d, deficiency is rare

5-methyl THF

Found in animal foods like beef liver.

Thiamin

Synthesized by animals with functional rumen and colonic bacteria; free form in plant foods (legumes, seeds, nuts, cereals, grains).

Thiamin diphosphate

Found in animal foods, mostly pork, also fish and eggs.

Vitamin B6

There are three different forms (pyridoxine or PN, pyridoxal or PL, and pyridoxamine or PM) all of which can have a phosphate derivative (PNP, PLP, PMP).

Vitamin B6 food sources

Most stable form is found in plant foods, such as whole grains, some vegetables (potatoes), some fruits (bananas), nuts, fortified cereals; also found in beef, fish, pork, chicken.

Vitamin B6 bioavailability

Impacted by prolonged heat exposure such as during sterilization for canning; not impacted by normal cooking processes.

Vitamin B12

Active coenzyme forms in the body are methylcobalamin and 5'-deoxyadenosylcobalamin; all types consumed are readily converted to these active forms.

Vitamin B12 sources

Animal products only! (and supplements of course); bound to proteins.

Riboflavin

Has 2 coenzyme derivatives, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).

Riboflavin food sources

Many foods, especially animal foods; milk and milk products have the most, then liver and meats.

Niacin

Richest sources are fish and meat; includes nicotinamide, NAD, NADP.

Biotin

Discovered when investigating 'egg white injury' (hair loss, dermatitis, neuromuscular problems); found in most foods and synthesized by colon bacteria.

Pantothenic acid

'Everywhere'; 85% is bound as a component of CoA, destroyed by heating and freezing, pH sensitive.

Vitamin C absorption

Does not require digestion, absorbed by intestinal cells as it is consumed; absorbed throughout small intestine, mostly proximal jejunum.

Vitamin C absorption rates

70-95% absorbed for usual intakes 30-100 mg, reduced to 50% absorption with large doses over 1g.

Folate digestion

Digested in jejunum by a zinc-dependent enzyme from pancreatic juice and bile or bound to the brush border enzyme; …… does not need to be digested.

Folate absorption

Occurs in proximal jejunum and duodenum; must be de-methylated for the transports to work.

Folate transport

Active carrier-dependent transport allows ….. to enter the bloodstream; transported as …… and 5-methyl-THF primarily.

Folate storage

Mostly stored in RBC than plasma.

Folate

RBC readings indicate longer-term status and is also stored in the liver.

THF and 5-methyl THF

Mostly stored forms of (……) which can be converted back to monoglutamate forms as needed.

Thiamin Digestion

Dephosphorylated by intestinal phosphatases to form free form (=no phosphate) and may be destroyed by anti-….. factors.

Anti-thiamin factors

Substances such as raw fish, phenols in coffee, tea, blueberries, red cabbage, alkaline environment, and excessive heat that can destroy thiamin.

Thiamin Absorption

Occurs in the intestines, especially the upper jejunum with some TDP uptake in the colon.

Thiamin Transporters

ThTr 1 can handle a larger volume, while ThTr 2 is more sensitive and able to take more in response to low thiamin intake.

Thiamin Passive Diffusion

Some passive diffusion can take place with high intakes around 5mg when carriers are saturated.

Thiamin Storage

We store small amounts with nearly half in the skeletal muscles, the rest in liver, kidney, heart, and brain.

Vitamin B6 Digestion

Must be dephosphorylated (if a phos form is ingested) by a zinc-dependent enzyme.

Vitamin B6 Absorption

Passive diffusion in the jejunum; released to portal blood, taken up by liver, metabolized to PLP for coenzyme function.

Vitamin B6 Storage

Bound to albumin in the cells; when cells are saturated, any unbound PLP is hydrolyzed to PL and released back into other cells.

Skeletal Muscle Storage of PLP

Stores about three quarters of our body's PLP bound to glycogen phosphorylase.

Vitamin B12 Digestion

Involves 6 steps; pharmacological doses absorb at about 1-3% with passive diffusion after typical absorption is saturated.

Vitamin B12 Transport

Lysosomes degrade the carriers and release B12 back into the cytosol; chaperones carry B12 throughout the cell.

Vitamin B12 Storage

Can be stored for a long time; deficiency may be prevented for 3-5 years if starting with full stores.

Riboflavin Digestion

Bound to proteins in food, must be released before absorption by hydrochloric acid and proteases.

Riboflavin Absorption

Occurs across the brush border membrane (proximal intestine, also some in the colon) by energy-dependent transporters; high absorption rate from food - 95%.

Riboflavin Transport and Storage

Can be converted back to FMN in the cell which requires ATP; stores last about 2-6 weeks, stored in liver, kidneys, heart.

Niacin Digestion

Phosphate hydrolysis takes place during digestion: NADP converted to NAD, then hydrolyzed to nicotinamide.

Niacin Absorption

Nicotinamide and any nicotinic acid are readily absorbed in the small intestine by facilitated diffusion, or in the colon by carrier transport.

Niacin Synthesis

60mg tryptophan ingested produces 1mg; depends on iron, B6 as PLP, riboflavin.

Biotin Digestion and Absorption

…… bound to protein requires enzymatic digestion before absorbing.

Pepsin and intestinal proteases

Enzymes that aid in the digestion of proteins.

Passive diffusion

The process by which substances move across membranes without the need for energy, predominating at high concentrations or pharmacological doses.

Carrier-mediated transport

Transport mechanism that requires specific carriers, such as SMVT, to move substances across cell membranes.

SMVT

A carrier shared by pantothenic acid and lipoic acid; its transcription is negatively affected by alcohol.

Pantothenic acid absorption

Occurs in the jejunum where the bound form is hydrolyzed for absorption.

Transport of pantothenic acid

Transported in portal blood and found in all tissues, with highest concentrations in liver, adrenal glands, kidneys, brain, and heart.

Vitamin C functions

Includes collagen synthesis, carnitine synthesis, catecholamine synthesis, and acting as an antioxidant.

Collagen synthesis

Vitamin C aids in the formation of ….. by reducing oxidized iron in the synthesis of hydroxyproline and hydroxylysine.

Carnitine synthesis

Vitamin C reduces iron in two steps of L-carnitine synthesis, which transports long-chain fatty acids for beta-oxidation.

Catecholamine synthesis

Vitamin C acts as a cofactor in converting dopamine to norepinephrine, which regulates the body's stress response.

Antioxidant role of Vitamin C

Donates electrons to free radicals to prevent damage to nucleic acids, fatty acids, and proteins.

Pro-oxidant potential of Vitamin C

Vitamin C can generate free radicals but does not do so in the human body.

Folate metabolism of choline

……… is converted through a series of reactions to dimethylglycine and then to glycine, requiring riboflavin as FAD.

Folate metabolism of serine

…… is converted to glycine, requiring THF and forming 5,10-methylene THF, with B6 as a cofactor.

Folate metabolism of methionine

Homocysteine is converted to ……….. through reactions requiring 5-methyl THF and cobalamin.

Synthesis of SAM

Methionine synthase produces …., a methyl donor involved in over 100 methylation reactions.

SAM levels and methionine

High SAM levels slow the conversion of homocysteine to methionine, while low SAM levels encourage re-methylation.

Gene expression and 5-methyl THF

Adequate …… …. enhances SAM availability for DNA synthesis.

Folate deficiency effects

Associated with decreased DNA methylation of tumor suppression genes, promoting cancer and increasing DNA strand breakage.

Pyrimidine synthesis

Folate-dependent process that is rate-limiting in DNA synthesis and replication.

Vitamin C

Regular use may reduce duration of cold symptoms.

Megaloblastic macrocytic anemia

One of the most common nutritional deficiencies, can occur after a few months of low intake.

Refeeding syndrome

Phosphate enters cells in large amounts to support ATP production. However, ATP production from glucose is thiamin-dependent.

Thiamin supplementation

Clinical consensus is to provide 200-300 mg daily for the first 7-14 days, then adjust as needed.

Beriberi

thiamin deficiency

• Early signs = fatigue & nausea/vomiting

• Dry beriberi = peripheral neuropathy, muscle weakness, and cramping

• Wet beriberi = tachycardia, right-sided heart failure, peripheral edema, cardiomegaly

• Wernicke-Korsakoff syndrome = ophthalmoplegia, horizontal nystagmus, ataxia, and confusion

Hypochromic microcytic anemia

Due to impaired heme synthesis. Low levels of hemoglobin. Iron deficiency

Megaloblastic macrocytic anemia

Because of methyl-folate trap. B12/ folate

Pernicious anemia

Inadequate IF, results in neurological issues. Can’t absorb b12

Casal's necklace

Like a sunburn in sun exposed areas. b3 - sign of pellagra

Vitamin C physical exam signs

Oral manifestations (bleeding gums), skin and hair follicle changes (petechiae and bruising), corkscrew hairs, hyperkeratosis.

Folate physical exam signs

Glossitis, pallor, onycorrhexis, diarrhea.

fatigue, shortness of breath, weakenss, headaches, heart palps, irritability/ conc. Issues, glosstis, diarrhea

Megoblastic macrocytic anemia

Thiamin physical exam signs

Fatigue, nausea,  dry beri beri, wet beri beri, Wernickes. Heart failure, Roger’s, reseeding relevant