Water soluble Vitamins

Vitamin C
Seaman eating dried biscuits and beef without fresh vegetables or fruit in the diet for long
periods of time experienced progressive weakness, pale colour of skin, bleeding gums,
haemorrhage, edema, ulcerations and finally death. The disease was named scurvy. Later it was
found that consumption of citrus fruit or juices could cure the disease which led to the discovery
of Vitamin C.
L – Ascorbic acid and L – Dehydroascorbic acid are physiologically active forms.

Ascorbic acid, which is a strong reducing agent, serves as an antioxidant and also, as a cofactor
in hydroxylation reaction.
It is essential for hydroxylation of proline and lysine to the hydroxyproline backbone and
hydroxylysine cross linkage needed for normal collagen fiber formation. Defects in this due to
lack of Vitamin C result in connective tissue diseases. In addition to the other effects due to this,
wound healing is also affected. Ascorbic acid is involved in carnitine and noradrenaline
formation also. Carnitine transport long chain fatty acids into mitochondria for oxidation.
Noradrenaline is a neurotransmitter and a hormone. Conversion of dopamine to noradrenaline is
dependent on ascorbic acid. It facilitates non-heme iron absorption from the digestive tract.
Absorption and metabolism
Actively absorbed and then freely circulate in blood and tissues. Approximately 85% of dietary
Vitamin C is absorbed. Excess is excreted by the kidney. Body ascorbic acid can reach 20 mg/kg.
Dietary sources
Major sources are fruits and vegetables. Citrus fruit, spinach, tomatoes, potatoes, broccoli and
strawberries are good sources.
RDA is 60 mg/day for adults. In the US smokers are recommended to increase their intake to 100
mg/day. In pregnancy 70 mg/day is recommended while for lactating mothers’ recommendation
is 95 mg/day.
Therapeutic use
Recommended for common cold. However, regular excessive intake could lead to problems.
Vitamin B
Vitamin B1 (Thiamin)
Beriberi occurred in epidemic proportions in Japan, China and Southeast Asia in the past due to
consumption of polished rice. Later crude form of thiamin was extracted from rice polishings.
Thiamin and Thiamin pyrophosphate (TPP)

Thiamin pyrophosphate serves as a coenzyme in many metabolic reactions which includes

carbohydrate metabolism, Krebs cycle and normal functioning of nervous system.
Absorption, metabolism and excretion
Actively absorbed in the proximal small intestine. Later a passive absorption also takes place if
thiamin concentrations are > 1 µmol. Alcohol inhibits active absorption but not passive
absorption. Thiamin circulates in the blood in free form. Part of the molecules are
phosphorylated and stored as TPP in tissues. Excreted with urine intact with small amounts of
metabolites.
Deficiency
Deficiency could occur due to inadequate intake, poor absorption or increased demand.
Excessive carbohydrate intake could increase the demand.
Beriberi caused due to deficiency is divided into ‘wet’ and ‘dry’ beriberi.
Wet beriberi – Symptoms are progressive dyspnoea (difficulty in breathing), edema, cardiac
failure, enlarged heart, vasodilation, pulmonary congestion.
Dry beriberi – Symptoms are superimposed with wet beriberi – extreme muscle weakness,
progressive polyneuropathy (simultaneous malfunction of many peripheral nerves throughout the
body).
Wernicke-Korsakoff syndrome
Chronic binge-drinking alcoholics could develop the disease, specially the ones who have
developed liver disease due to low TPP. Paralysis of ocular muscles, wide based gait, global
confusional state and amnesia (memory loss) are the symptoms.
Quantification
HPLC and HPLC-MS are the most accurate method of analysis. As thiamin and derivatives are
mostly in red blood cells whole blood is used for analysis.
Dietary sources
Plant seeds, mainly unrefined cereal grains are a good source. In addition, organ meats, pork,
nuts and legumes are good sources.
RDA – Refer to the tables recommended.
Therapeutic use and toxicity
Patients with wet beriberi are given intramuscular doses of 25 mg followed by 3 daily oral doses
of 10 mg. Patients with dry beriberi with peripheral neuropathy respond slowly to the treatment.
Patients with Wernicke-Korsakoff syndrome may respond depending on how advanced the
disease is.
No known toxicities are associated with thiamin.
Vitamin B12 – Cobalamin
Substitutions at R include,
• CN – Cyanocobalamin
• OH – Hydroxycobalamin
• CH3 – Methylcobalamin
• 5-Deoxyadenosyl – 5-Deoxyadenosylcobalamin
Natural dietary forms are Hydroxycobalamin, Methylcobalamin and 5-
Deoxyadenosylcobalamin. Cyanocobalamin is a therapeutic product.
Vitamin B12 is a cofactor for two enzymes, Methionine synthetase and Methyl-Malonyl-CoA
mutase. Methionine synthetase catalyzes the methyl-Cobalamin dependent (re)methylation of
homocysteine to methionine within the methionine cycle. A reaction required to produce this
essential amino acid and generate S-adenosylmethionine, the most important cellular methyl-
donor. Disruption of methionine synthase has wide-ranging implications for all methylation-
dependent reactions, including epigenetic modification, and also, for the intracellular folate
pathway, since methionine synthase uses 5-methyltetrahydrofolate as a one-carbon donor. Folate-
bound one-carbon units are also required for deoxythymidine monophosphate and de novo
purine synthesis.
Methyl-Malonyl-CoA mutase convert methylmalonyl CoA to succinyl CoA. Reaction occurs in
mitochondria with deoxyadenosylcobalamin as cofactor. Reaction is essential for degradation of
propionate and odd chain fatty acids. Deficiency results in accumulation of methylmalonic acid,
with acidosis and high serum glycine and glucose concentrations.
Absorption metabolism and excretion
About 70% is absorbed bound to carrier proteins and taken to liver. It is taken up by specific
receptors. Excreted in urine and feces (50:50%).
Deficiency
Generally, deficiencies arise due to gastrointestinal diseases which reduce absorption rather than
reduced intake. Dietary vitamin B12 comes exclusively from animal sources. Therefore,
vegetarians and specially vegans could have deficiency. However, deficiency is very rare as
gastrointestinal bacteria produce adequate amounts.
Pernicious anaemia is mainly caused by a decrease in red blood cells due to inability to absorb
vitamin B12. Vitamin B12 therapy usually corrects the deficiency.
Assessment
Both vitamin B12 and folate are involved in methionine synthesis. Therefore, deficiency of both
will increase precursor homocysteine levels. However, increased urinary excretion of
methylmalonic acids distinguishes vitamin B 12 deficiency as it is specific for methylmalonyl CoA
conversion to succinyl CoA. GC analysis of both serum and urine is used for detection.
Dietary sources
Found only in food from animal sources. Synthesis by gut microorganisms may provide adequate
amounts in vegetarians. However, vegetarians are advised to consult a nutritionist to check
whether they need supplements.
Vitamin B9 Folate (Folic acid)

Folic acid (pteroylglutamic acid) is composed of three large sub-components. These are the
pteridine ring, para-amino benzoic acid, and glutamic acid.
A deficiency in folic acid can lead to a range of health problems. Some common symptoms of
folic acid deficiency include fatigue, weakness, shortness of breath, pale skin and a swollen
tongue. It can also lead to anemia. In pregnant women, folic acid deficiency can increase the risk
of neural tube defects (spina bifida) in the developing fetus. This is why it is recommended for
women planning a baby or in the early stages of pregnancy to take folic acid supplements.
Folate is hydrolyzed and absorbed. Liver is the main storage. Dietary sources are green leafy
vegetables, nuts, grains and liver. Folate supplementation is recommended in pregnancy.

Vitamin B6 (Pyridoxin)

Vitamin B6 occurs naturally in three forms. Pyridoxine, pyridoxal and pyridoxamine. All three
forms undergo phosphorylation at 5 position to give pyridoxal phosphate (PLP) which is a
coenzyme. It is a coenzyme for many reactions related to protein metabolism. e.g.
aminotransferase and decarboxylases.
PLP dependent decarboxylation is required in the formation of several amines including
epinephrine, norepinephrine and serotonin. It is involved in heme formation, glycogen
metabolism, sphingolipid synthesis in nervous system and synthesis of niacin from tryptophan.
Absorption metabolism and excretion
Predominantly phosphorylated dietary B6 are hydrolyzed by alkaline phosphatase and absorbed.
Re-phosphorylation occurs in the liver. PLP circulates in blood bound to albumin.
In metabolism PLP is converted to free pyridoxal by alkaline phosphatase. Then converted to
pyridoxic acid which is the principal metabolite excreted by kidney.
Deficiency
Symptoms include inflammation of the tung, lesions on the lips and corners of the mouth and
peripheral neuropathy. Mostly alcoholics have deficiency.
Poultry, fish, pork, egg, liver and kidneys are rich dietary sources. Soybeans, oats, peanuts and
unpolished rice are also good sources.

Vitamin B3 – Niacin

A – Nicotinic acid, B - Nicotinamide

Niacin is the generic name for nicotinic acid and its natural derivative nicotinamide
(niacinamide).
Nicotinamide is incorporated within NAD or NADP where its function as a factor for many
oxidoreductases involved in glycolysis, fatty acid metabolism, tissue respiration and
detoxification. It is present in the diet bound to coenzymes (proteins) as niacin. It is hydrolyzed
to nicotinic acid, nicotinamide and nicotinic mononucleotide (NMN) and absorbed from the
digestive tract.
Deficiency causes pellagra. It affects the whole body and can eventually lead to death.
Symptoms of pellagra include delusions or mental confusion, diarrhea, weakness, loss of
appetite, pain in abdomen, inflamed mucous membrane scaly skin sores, especially in sun-
exposed areas of the skin.
Method of assessment
Urinary excretion of metabolite 1-methylnicotinamide is decreased in deficiency and therefore
used for assessment. Spectrophotometry is used in the assay.
Dietary sources
Meat is a rich source. Cereals such as oats, rice and wheat provide moderate amounts with lesser
amounts in corn. Bioavailability of niacin from cereals is variable and increased by treatment
with lime water (Calcium hydroxide). The absence of pellagra in ancient Mayans while
occurrence in others with similar diets is because Mayans treated corn with lime.
Patients with pellagra quickly respond to 1-2 g of nicotinic acid or nicotinamide daily.
Vitamin B2 - Riboflavin
Riboflavin contains an isoalloxazine ring linked to ribityl side chain. An ester phosphate linkage
in ribityl chain gives flavin mononucleotide (FMN). FMN can be linked to adenine
monophosphate to form flavin adenine dinucleotide (FAD). Flavoprotein enzymes containing
FMN or FAD are bound to many apoenzymes and are involved in oxidation-reduction reaction in
many metabolic pathways and affects cellular respiration.
Absorption, metabolism and excretion
Acidic conditions in the stomach release FAD and FMN from proteins. Then hydrolyzed by
pyrophosphatase and phosphatase to release free riboflavin in the intestine. Riboflavin is
absorbed and phosphorylated to FMN in enterocytes. Riboflavin and metabolites are mainly
stored in the liver and also in the kidney and heart. FAD is the main storage form (70 -90%).
They circulate in blood bound to albumin. About 200 µg of riboflavin and metabolites are
excreted in urine daily.
Riboflavin deficiency can cause fatigue, swollen throat, blurred vision, and depression. It can
affect the skin by causing skin cracks, itching, and dermatitis around the mouth. Hyperemia (The
presence of an increased amount of blood in a body part or an organ) and edema around the
throat, liver degeneration, and hair loss can also occur along with reproductive issues.
Assessment
Measuring of riboflavin in urine and red blood cells. UV/VIS spectrometry can be used for assay
in aqueous media.
Dietary sources
Dairy products, poultry, meat, fish, asparagus, broccoli and spinach are the main dietary sources.
Vitamin B7 - Biotin
Biotin is a cofactor in several carboxylases in fatty acid synthesis and metabolism,
gluconeogenesis and branched chain amino acid metabolism.
Absorption, metabolism and excretion
Protein bound vitamin is hydrolyzed to biocytin and actively absorbed along with free biotin in
small intestine. Stored in liver, muscle or kidney. Biocytin is hydrolyzed to biotin in plasma.
Biotin and metabolites are excreted in urine. Biotin is synthesized by colonic bacteria and daily
fecal biotin excretion is 3-6 times dietary intake.
Deficiency
Biotin deficiency is very rare.
Deficiency cause fatigue, nausea, anorexia, muscle pains, dry scaly skin, anemia, elevated serum
cholesterol, alopecia (hair loss in patches), paraesthesia (an abnormal sensation, typically
tingling or pricking (‘pins and needles’), caused mainly by pressure on or damage to
peripheral nerves.).
Dietary sources
Liver, egg yolk, soy flour, cereals and yeast are good sources. Wheat contains biotin in bound
unavailable form.
Vitamin B5 – Pantothenic acid

Pantothenic acid is converted to 4-phosphopantatheine and Co enzyme A (CoA) which is the

primary active form.
Coenzyme A is essential in lipid and carbohydrate metabolism. It is involved in steroid hormone
synthesis also.
Absorption and metabolism
Pantothenic acids are ingested as part of the CoA. Hydrolyzed by intestinal phosphatases to give
phosphopantetheine and pantothenic acid the absorbable forms. CoA is resynthesized in liver.
Pantothenic acid is excreted in urine mainly as metabolites of CoA.
Human deficiency is very rare. Deficiency cause fatigue, insomnia, depression, irritability,
vomiting, stomach pains, burning feet, and upper respiratory infections.
Dietary sources
Pantothenic acid is widely distributed in nature. Animal products, whole grains and legumes are
good sources.