Mary M. Fynn, Ph.D, RD, L.D.N

Water soluble vitamins

Water soluble vitamins

January 2016

Vitamins

 Vitamins are organic compounds that cannot be synthesized by humans.  They are either water or fat soluble.  All vitamins have a deficiency disease associated with them, which is how most of them were discovered.  All of the vitamins can be obtained from food.  It is not necessary to rely on vitamins as pills/ supplements. In fact, use of dietary supplements is more likely to cause harm than benefit.  A law passed in 1994 (Dietary Supplement Health and Education Act/DSHEA) took the regulation of the vitamin/ mineral/ herb industry away from the FDA and gave it to the USDA as it classified these pills as “food”.  Lack of FDA oversight means that these products are no longer well controlled and their safety does not need to be proven prior marketing.

Water soluble vitamins

The water-soluble vitamins are all the B vitamins and vitamin C.  The water-soluble vitamin, in general, can be stored in limited quantities in the body.  Food consumption studies indicate that the food supply of the B vitamins and C is adequate.  Deficiencies of the water soluble vitamins are not common in the US.  Flour sold in the US is fortified with some of the B vitamins (thiamin, riboflavin, niacin, and folic acid), white flour (and products made from white flour) a major source of these vitamins.  The milling of flour removes the germ and bran, which supply micronutrients and phytonutrients.  Whole grain contains more B6, vitamin E, magnesium, zinc, and fiber.  Milling leaves the endosperm, which is nutrient poor.  Iron is also added to flour in the US, but humans do not easily absorb the form of iron added.

As a general statement, the water-soluble vitamins are thought to be less toxic than the fat soluble vitamins as they are less readily stored.  However, due to the increase use of mega- doses of vitamins in the past 20 years, toxic effects of water-soluble vitamins could become known.

Function: part of coenzyme TPP (thiamin pyrophosphate).  TPP+ an enzyme allows for oxidative decarboxylation (e.g., pyruvate to acetyl-CoA).  This allows for complete catabolism of glucose in metabolism.

Deficiency:  symptoms are related to disorder of nerve function, as thiamin deficiency reduces the production of ATP by slowing the TCA cycle.  Systems affected are cardiovascular, nervous, and gastrointestinal.  A diet lacking in thiamin can produce symptoms in as little as 7 days with anorexia, weight loss, irritability, headache, fatigue, depression, and weakness.  Severe deficiency produces beriberi, which can be common with diets relying on rice that is not enriched.  Wernicke-Korsakoff syndrome is thiamin deficiency found in chronic alcoholics.  It can result from dietary lack or impaired absorption.  The symptoms include apathy, memory loss, and eyeball movement that is rhythmic.

Dietary sources: a number of foods contain thiamin, but in small amounts.  Major dietary sources are white flour products (bread, rolls, crackers) due to enrichment, pork, processed meat, cereals, orange juice, legumes, wheat germ, green beans, asparagus, and mushrooms.  Thiamin is lost with prolonged heat, and with an alkaline environment (pH >8.0).

Functions: part of 2 coenzymes: FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide) which is formed by the transfer of AMP from ATP to FMN.  FAD and FMN are involved in many oxidation-reduction reactions, e.g., TCA cycle and beta-oxidation.  The coenzyme is reduced and the electrons are then donated to the electron transport chain.

Deficiency: a pure riboflavin deficiency manifests as tongue inflammation, cracking of the tissue around the mouth, inflammation of the mouth and throat. Riboflavin deficiency is usually present with other B vitamin deficiencies and you will see a general failure of metabolic pathways.

Dietary sources: a major food source of riboflavin is dairy products, so a diet without dairy products increases the risk of deficiency.  Riboflavin breaks down with light exposure, which is why most milk containers are not clear glass.  Other food sources are enriched flour products, eggs and meat, mushrooms, spinach, and broccoli.

Nicotinamide is nicotinic acid with an amide group instead of a carboxyl group.  This form can be deaminated and is equivalent to nicotinic acid.

Functions: part of 2 coenzymes that function in oxidation-reduction reactions: NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate).  More than 200 metabolic pathways require NAD for oxidative/ reduction reactions.  NAD functions in catabolic pathways (glycolysis and TCA cycle).  In glycolysis, NAD is reduced to NADH.  If the environment is aerobic, the “H” is carried to the electron transport chain.  If anaerobic, the “H” is transferred to pyruvate to produce lactic acid.  This frees up the NAD to keep glycolysis going.  NADPH is the reduced form of NADP and is required in fatty acid synthesis (an anabolic pathway).

Deficiency: pellagra (Italian – pelle = skin and agra = rough).  One of the symptoms of pellagra is rough, painful skin.  Pellagra causes widespread damage as so many steps in metabolism require NAD.  Pellagra symptoms are the 4 D’s: dermatitis, diarrhea, dementia, and if untreated, death.

Medicinal use of niacin:  in 1955 it was discovered that large doses of niacin can lower blood levels of triglycerides. The dose of niacin needed is 1.5 to 3 g; in comparison, the requirement for niacin is set as 15 mg for women and 19 mg for men. Niacin in high doses acts by decreasing the release of free fatty acids from the adipose tissue, which leads to a decrease in VLDL production in the liver.  Niacin is most effective in reducing triglycerides up to about 300 mg/dl; this reduction leads to a corresponding increase in HDL-c.  Triglyceride reduction averages 10-40% and HDL increases typically 5 to 20% (the increase in HDL is dependent on the decrease in triglycerides).  The side effects of large doses of niacin are flushing, itching, nausea, and liver damage.  Some patients find the itching intolerable.  Patients using large doses of niacin require periodic liver function tests.

Dietary sources: wheat products, mushrooms, wheat bran, tuna fish, meat, chicken, asparagus, and peanuts contain the majority of dietary niacin.  The amino acid tryptophan can be con

Function: part of coenzyme A, which functions in the transfer of acyl groups (e.g., acetyl CoA, fatty acyl CoA).  Also, pantothenic acid is part of fatty acid synthase, the enzyme that makes fatty acids.

Deficiency: A deficiency of pantothenic acid does not have a specific name, as it overlaps with other B vitamin deficiencies and is not common on its own.  Symptoms are thought to include headache, fatigue, impaired muscle coordination.

Dietary sources: meat, milk, vegetables, mushrooms, liver, peanuts, eggs, and broccoli.

Biotin

Functions:  coenzyme in carboxylation reactions (e.g., in the liver, pyruvate + CO2 yields oxaloacetate).

Deficiency: a deficiency of biotin results in dermatitis, loss of appetite and nausea.  While a deficiency is rare, a protein in raw egg (avidin) will bind biotin, which inhibits absorption.  It typically requires 12 to 24 eggs for this to occur.

Dietary sources:  the biotin content of foods has not been well studied, but it is found in whole grains, egg yolks, nuts, and legumes.  Biotin is also synthesized by the bacteria of the gi tract and this is thought to be a major contributor.

B6 is a family of 3 compounds: pyridoxal, pyridoxine, pyridoxamine.  These can all be phosphorylated, which makes the active B6 coenzyme: pyridoxal phosphate (PLP).

Functions:

  1. required for transamination.  If B6 is deficient, all amino acids are essential.  B6 is also required by decarboxylase, an enzyme that removes CO2 from amino acids.
  2. one of the vitamins needed for conversion of homocysteine to cysteine (methionine metabolism).  Elevated levels of homocysteine will increase oxidation and have been linked to atherosclerosis.
  3. synthesis of the hemoglobin ring structure.
  4. conversion of tryptophan to niacin.

Deficiency: a deficiency of B6 is rare, but can occur in infants on formula that contain inadequate levels of B6.  A deficiency of B6 can result in high blood levels of homocysteine, which would increase oxidation and the development of atherosclerosis.

Toxicity:  B6 was one of the first water soluble vitamins to produce an observable toxicity when consumed in mega-doses.  This occurred in the 1980’s when B6 was prescribed for PMS (premenstrual syndrome).  It was incorrectly assumed that large doses of B6 would treat the “psychological problems” of PMS.  The dose prescribed was 2-6 mg/day (requirement is 1.5 mg/day for women).  Toxicity symptoms were produced after 2-40 months of the mega dose.  Symptoms of the toxicity were numbness of hands and feet and some partial paralysis was also reported.  Most of the symptoms subsided (but not eliminated) when the supplement was stopped.  Smaller doses (100-200 mg) have been used to treat carpal tunnel syndrome with mixed results.

Dietary sources of B6:  B6 is more readily available from animal sources and is found in meat, fish, and poultry (B6 is part of skeletal muscle).  Plant sources of B6 are banana, broccoli, spinach, and whole grain (B6 is lost in the refining of flour and it is not added back).

Folate is converted to the coenzyme THFA (tetrahydrofolic acid).  B12 is required to release the folate from the THFA; thus, a deficiency of B12 will manifest as a folate deficiency.  Folate is the dietary source of the vitamin and folic acid is found in supplements.

Functions:

  1. synthesis of purines and thymidine, which are needed to make DNA, thus folate is required for cell growth/ division.
  2. amino acid metabolism: folate is needed in transamination, including the conversion of homocysteine to methionine.

Deficiency:  a deficiency of folate can result from an intake insufficient to meet demand (e.g. pregnancy), poor absorption, or not being able to release folate from THFA.  The latter is often the result of B12 deficiency in the presence of adequate folate status.  A deficiency of folate affects cells actively dividing and those with a short life span.  For example:

  1. the precursor cells for red blood cells (RBC) in bone marrow do not mature to RBC leading to megaloblastic anemia – large, immature RBS’s.  This can be identified clinically by an increase in MCV (mean corpuscular volume).
  2. absorptive cells in the gastrointestinal tract are not readily replenished resulting in decreased absorption and persistent diarrhea.
  3. folate is needed in the first 28 days of life after conception.  A deficiency can lead to neural tube defects (NTD).  The source of the problem can be either low folate intake or a genetic ability of the mother to properly use folate.  This is part of the reason for folic acid being fortified into flour.

Toxicity:  a toxicity of folate is rare as the FDA limits the amount of folic acid in nonprescription supplements.  The concern is that large doses of folic acid can mask a B12 deficiency.  Folic acid is the supplement form of the vitamin and it is more readily absorbed than folate (found in food), especially if the supplement is taken without food.

Dietary sources of folate:  the word “folate” comes from “folium”, which is Latin for “leaf”.  The main dietary sources of folate are leafy greens – collard greens, kale, spinach, etc.   Folate is also found in broccoli, asparagus, organ meats, and oranges. Folate is easily destroyed with heat and/or excess oxygen exposure.  Folic acid is the form of the vitamin in supplements (pills) and also fortified into foods, such as enriched flour and breakfast cereals.  Folic acid is more easily absorbed as the dose is large in pills and is absorbed by passive diffusion.

Functions:

  1. required to release folate from THFA
  2. required in the conversion of homocysteine to methionine
  3. isomerization of methylmalonyl CoA – produced in the degradation of some amino acids and also in the degradation of fatty acids with an odd number of carbons in the chain.

Deficiency:  a deficiency of B12 can produce megaloblastic anemia, which is secondary to folate deficiency.  Providing sufficient folate can cure the anemia, but if it truly a B12 deficiency there will also be nerve damage, which can produce dementia and if not corrected, can be fatal.  The nerve damage is thought to result from the accumulation of abnormal fatty acids that incorporate in the cell membrane of the nervous system.  Symptoms of the nerve damage resulting from B12 deficiency are tingling and numbness in the legs, which is worse in the lower legs, mental disturbances, such as loss of concentration, disorientation, and dementia.

The ability to absorb B12 from food is more complicated than seen with other vitamins.  B12 is bound to a protein in food.  It is released in the stomach by HCL (hydrochloric acid) and pepsin, and rebound to a new protein (R-protein).  When the complex moves to the duodenum, the pancreatic proteases release the B12 from the R-protein and B12 then binds to “intrinsic factor” (a glycoprotein produced by the stomach parietal cells).  The complex travels to the ileum, where it is absorbed into the portal system and bound to a specific blood protein, which brings it to the liver.  Typically, about 50% of the B12 in food is absorbed.  B12 is secreted with the bile into the small intestines and recycled with enterohepatic recirculation.

The absorption of B12 can be hampered by a number of situation; e.g., genetic disorders that prevent synthesis of one or more of the intestinal carrier proteins; removal of part of the stomach and/ or the ileum; certain medications and aging, which reduce stomach acidity.  A B12 deficiency is more likely to be due to a problem with absorption then inadequate intake.  In B12 deficiency, B12 needs to either be injected or as a nasal spray (to bypass the gut), or consumed in mega doses, which allow for absorption by passive diffusion.

A B12 deficiency may occur in someone who has been a vegan for a number of years.  As B12 is recycled via enterohepatic recirculation, the time to depletion/ deficiency will depend on the baseline stores.  B12 deficiency is also a concern in the elderly, due to the potential for inadequate absorption.

Dietary sources of B12:  all B12 is synthesized by bacteria, fungi, and algae.  The only reliable food source of B12 is animal products (all meat/ poultry/ seafood, eggs, and dairy). B12 is particularly high in organ meats and hot dogs made with organ parts.  B12 is not found naturally in plant sources.

There are two forms of vitamin C: ascorbic acid (the reduced form) and dehydroascorbic acid (the oxidized form).

Functions:

  1. non-specific reducing agent – this function is related to many of the other functions.
  2. collagen synthesis – collagen is 3 polypeptide chains which form a fibrous protein; when formed, it gives the strength to connective tissue.  Vitamin C is needed for the enzymes to form the helix of the polypeptide chains.  Vitamin C reduces the metals needed for the enzyme to function.  Collagen is a major component of bones, blood vessels, and the tissue produced with wound healing.
  3. antioxidant – ascorbic acid is a water-soluble antioxidant.  Vitamin C is thought to work with vitamin E (a fat-soluble antioxidant).
  4. iron absorption – vitamin C increases the absorption of non-heme iron (plant sources of iron).
  5. immune function – white blood cells (WBS) have the highest concentration of vitamin C in the body.  Vitamin C may function in the WBC to protect it from oxidative damage.

Deficiency:  a deficiency of ascorbic acid causes scurvy.  The symptoms of scurvy result from an inability to synthesize collagen.  Scurvy starts with fatigue, then pinpoint hemorrhages; next is bleeding of gums and wounds that have healed can reopen.  Scurvy can develop after 20-30 days without vitamin C.  Populations of concern are the elderly with inadequate intake, and other age groups with a consistent adequate intake (e.g., the food insecure).  Smokers have an increase need for vitamin C due to increased oxidation, particularly in the lung tissue.

Toxicity:  vitamin C may be the first, and still the most common, vitamin to be used in widespread mega doses.  The RDA for vitamin C is 75-90 mg/day; most supplements have at least 500 mg per pill.  The absorption of vitamin C decreases with large doses, with approximately 70-90% absorption with an intake of 30 to 180 mg, which decreases to 50% at 1g (1000 mg).  The common side effect of high intake is nausea, intestinal cramping, and diarrhea, resulting from the vitamin not been absorbed, which draws fluid into the intestines.   There is no evidence that vitamin C in high doses will decrease the frequency or severity of the common cold.

Dietary sources of vitamin C:  vitamin C is found naturally in citrus fruits, potatoes, tomatoes, green peppers, broccoli, and strawberries.  It is also fortified into many juice and fruit drink products.  Vitamin C is easily lost in processing and with heat (cooking).  The vitamin C that is fortified into juices has been shown to be unstable in the presence of heat, oxygen, iron, and/or copper.