Vitamins are vital to life! In the 1930’s, nutrition was the most important medicine because it cured so many diseases. The 1st vitamin was discovered in 1915. They are named alphabetically. F & G were dropped… I don’t know why. The B complex was later sub-divided after more properties were discovered. Standard nomenclature for vitamins was established in 1979.

They are needed in small amounts in the diet to help regulate and support chemical reactions in the body. Generally, they can’t be synthesized in the body (exceptions: Vitamin D, K, niacin, & biotin). In order for a substance to be considered a vitamin, absence of the chemical must produce deficiency symptoms that are eliminated quickly once the substance is re-supplied.

RDA= Recommended Dietary Allowance. The RDA is set at a level that is 20% of the maximum level that produces symptoms of deficiency. In other words, if you can still have symptoms of deficiency at 10 mg per day (but not at 10.1 mg/d) then the RDA would be set at 12 mg per day. Keep in mind that this may not be the level for optimal health!

DRI = Dietary Reference Intake

The vitamins are divided into 2 catagories:

Water Soluble Vitamins: They are generally not stored in the body and require a daily intake.

The B Vitamins (Thiamine, Riboflavin, Niacin, Pantothenic Acid, Biotin, Vitamin B6, Folic Acid, Vitamin B12) and vitamin C

Fat Soluble Vitamins: Fat is needed in the diet to absorb them. They are probably absorbed through lymphatics (as opposed to venous blood) due to fat absorption. They are stored in body tissues and not needed in the diet daily. They are more likely to be toxic and less likely to be decreased or destroyed due to cooking.

  • Vitamins A
  • Vitamin D
  • Vitamin E
  • Vitamin K

Vitamin A

VITAMIN A

Vitamin A is actually a family of similar compounds, the retinoids, that are related to retinol. Apparently, retinoic acid performs most of the functions of vitamin A, binding to DNA receptors in target cells. You can see the diagram of this and it might make more sense.

As far as I can tell, there are 4 biologically important retinoids:

  • Retinol– the alcohol form
  • Retinal– the oxidized form of retinol. The two are readily convertable.
  • Retinoic Acid– the oxidized form of retinal. It cannot be reduced in the body. Thus, it cannot give rise to retinol or retinal. It has wide pharmacologic therapies in dermatology.
  • β-carotene– plant form of vitamin A. Oxidatively cleaved (via thyroid hormone) in the intestine to 2 molecules of retinal. Unfortunately, this conversion process is inefficient and the vitamin A activity of β-carotene is only about 1/6 that of retinol.

RDA: for adults- 1000 retinol equivalents (RE) for males and 800 RE for females. One RE=1 mg of retinol; 6 mg of β-carotene; or 12 mg of other carotenoids.

Good sources of Vitamin A: liver, kidney, cream, butter, and egg yolks have pre-formed vitamin A. Yellow and dark green vegetables and fruits are good sources of carotenes.

Functions of Vitamin A: The functions of vitamin A can be divided into four categories.

  • Visual Cycle- I could describe this part in detail but a picture is worth a thousand words (and since I ramble on so much) you can see this better in the diagram.
  • Growth- Absence of vitamin A prevents bone growth from keeping up with the growth of nervous tissue and can lead to CNS damage. Also, there is a hyper-keratinization of the taste buds on the tongue which decreases the person’s appetite (at first anyway).
  • Reproduction- prevents fetal resorption in the female and supports spermatogenesis in the male. Retinoic acid doesn’t help here or with the visual cycle. Therefore, if anyone has only had retinoic acid since birth, they are blind and sterile.
  • Maintenance of Epithelial Cells- you gotta have this stuff for epithelial differentiation and mucous secretion.
  • Retinoic acid as a pharmacotherapeutic- effective treatment of acne and psoriasis. Everything I have seen states that you have to use an all trans retinoic acid (tretinoin) which is too toxic for systemic use and must only be applied topically. However, if the pt doesn’t respond to this therapy, and if they have a severe case, you can use isotretinoin (13-cis retinoic acid) P.O.
  • b-carotene- Populations that consume increased amounts of b-carotene also have a reduction in heart disease and lung and skin cancer. These effects are independent of β-carotene being a precursor to vitamin A and probably due to its antioxidant effects (see oxidative damage). β-carotene, unlike vitamin A, is not toxic even at high doses.

Toxicity: Some would argue that this can be the most toxic of the vitamins. You shouldn’t exceed 7.5 mg per day of retinol. Acute toxicity can be fatal. Chronic toxicity symptoms include alopecia, liver damage, cracking and bleeding heals, dry and pruritic skin, and orange skin. Can also increase intracranial pressure (CNS Sx).

Deficiency Symptoms: Night blindness, xerophthalmia, dry-rough skin, impaired bone growth.  Vitamin A deficiency is the most common deficiency in the world and the 2nd leading cause of blindness (second only to Chlamydia trachomatis).
Vitamin B1 (Thiamine)

VITAMIN B1 (THIAMINE)

The active form of thiamine is thiamine pyrophosphate (TPP) which is essential for the conversion of pyruvate to acetyl CoA and Step 4 of the Kreb’s cycle. It is also essential for the conversion of glyceraldehyde-3-phosphate (one of the glycolysis intermediates) to ribose-3-phosphate. I have included the diagram for the transketolase pathway here:

Good sources: Sunflower seeds, liver, pork, whole and enriched grains, and dried beans. According to one source, the outer layer of seeds is high in thiamine. Thus, whole wheat breads are high in thiamine while bread made from milled grain is low in thiamine.

DRI: 0.9-1.2 mg per day

Functions: the functions of this vitamin are listed above. It also assists in nerve function.

Deficiencies: Beri-Beri which means “I can’t, I can’t.” Infantile beri-beri symptoms include: tachycardia, vomiting, convulsions, and death. Adult beri-beri symptoms are: dry-skin, irritability, disorderly thinking, and progressive paralysis. Alcoholics are particularly at risk for thiamine deficiency for two reasons. First of all, they are likely to have a reduced intake and, secondly, alcohol decreases thiamine absorption.

Toxicity: Thiamine is not considered toxic. However, some have linked head aches and insomnia to thiamine when their doses exceeded 5 mg/d for 4-5 wks.

Vitamin B2 (Riboflavin)

VITAMIN B2 (RIBOFLAVIN)

Riboflavin is needed for the formation of flavin mononucleotide (FMN, seen in Complex I of the ETS) and flavin adenine dinucleotide (FAD, from Step 6 of the Krebs). Below is a diagram that shows their structures.

Riboflavin is light-sensitive! That’s why you won’t see milk in a clear bottle or container.

Good sources: Milk, eggs, liver, green leafy veggies, and whole & enriched grains.

DRI: 0.9-1.3 mg per day

Functions: The 2 co-enzymes discussed above (FMN and FAD).

Deficiencies: Dermatitis, glossitis, corneal vascularization

Toxicity: None known. That’s not to say there isn’t one… we (I) just don’t know about it!

Vitamin B3 (Niacin)

VITAMIN B3 (NIACIN)

Good sources:meats, liver, nuts, whole and enriched grains. Some niacin can be synthesized from tryptophan (inefficient).

DRI: 12-16 mg/d

Functions: Co-enzyme formation (NADand NADP), fatty acid metabolism, and decrease serum cholesterol. It is the most potent agent to increase serum HDL at doses 100 times the RDA (but most people can’t tolerate the side effects). It does this by strongly inhibiting lipolysis in adipose tissue, which is the largest producer of circulating FFA’s. Decreased FFA’s are needed for the formation of VLDLs. LDLs are produced from VLDLs. Thus, niacin inhibits the formation of  LDLs (indirectly). It is especially useful for the treatment of type IIb hyperlipidemia (both VLDL and LDL levels are increased).

Deficiencies: Pellegra (the 3 D’s: Diarrhea, Dermatitis, Dementia) and death (eventually).

Toxicity: Histamine reaction at doses >35 mg. Facial flushing is one of the symptoms of this and can be treated with many modalities. I typically recommend taking niacin supplements at night, before bed, and with food. Applesauce is, apparently, a miracle substance that can prevent some of the side effects.
Pantothenic Acid

PANTOTHENIC ACID

It means “it’s everywhere”

Good sources: Liver, broccoli, and egg yolks.

DRI: 4-5 mg/d. No RDA has been set.

Functions: It is the precursor to Co-enzyme A (CoA) as in acetyl CoA or succinyl CoA (see glycolysis or Kreb’s cycle).

Deficiencies: Not well characterized in humans. Tingling in hands, fatigue, head aches, and N/V

Toxicities: None known
Biotin

BIOTIN

Good sources: Cheese, egg yolks, milk, peanut butter, & liver.

DRI: 20-30 mg/d

Functions: Co-enzyme in glucose production and fat synthesis.

Deficiencies: Pale, dry skin; depression; poor appetite (not common).

Toxicities: None known
Vitamin B6 (Pyridoxine)

VITAMIN B6 (PYRIDOXINE)

Actually a group of chemicals: pyridoxine, pyridoxal, and pyridoxamine. Pyridoxine is found in plants and the other two are found mainly in animals. Pyridoxal phosphate is the biologically active co-enzyme.

Good sources: Animal proteins, spinich, broccoli, bananas, wheat, corn, egg yolk, liver.

DRI: 1-1.7 mg/d. However, the requirement for pyridoxine goes up when you have a high protein intake.

Functions: Co-enzyme in protein metabolism, neurotransmitter synthesis, Hgb synthesis, homocysteine breakdown

Deficiencies: Convulsion, nausea, flaky skin, HA, insomnia (uncommon). Isoniazid can induce a  deficiency, so you have to supplement with isoniazid prescription. Deficiency is rare but has been seen in infants with low intake of B6, females on OCP’s, and alcoholics.

Toxicity: Nerve damage (it is the most toxic water soluble vitamin) at doses > 200mg. Substantial improvement, but not complete recovery, occurs when the vitamin is removed. Another source indicated neurologic symptoms at doses of 2 grams/d. You gotta love ambiguity!
Folic Acid (Folate)

FOLIC ACID (FOLATE)

Good sources: Green leafy veggies, liver, lima beans, and whole grain cereals

DRI: 300-400 mg/d (0.3-0.4 mg/d); for women who are on birth control pills, this increases dramatically. After d/c’ing BCPs, they must take 800 mg/d for at least 30 days before getting pregnant.

Functions: Folic acid is essential for the biosynthesis of the purines and the pyrimidine , thymine. It is converted to tetrahydrofolic acid (THF) which is the biologically active form. THF receives one-carbon fragments from donors (ie. serine, glycine, & histidine) and transfers them to intermediates in the synthesis of amino acids and the nucleotides mentioned above. See the diagram below.

Deficiencies: Folic acid deficiency is probably the most common vitamin deficiency in the U.S. (especially amoung pregnant females and alcoholics). Deficiency is manifested two ways: the first is Megaloblastic anemia because there isn’t enough synthesized nucleotides; the second is developmental abnormalities of the neural tube in the fetus.

The anemia is due to diminished synthesis of purines and thymidine. Therefore, the erythropoeitic cells are not able to make DNA or divide. Vitamin B12 deficiency can also cause this disorder (but at a different step). Make sure to evaluate the exact cause of megaloblastic anemia before instituting therapy. Deficiency can be brought on by increased demand (as in pregnant or lactating women), poor absorption, alcoholism, or medications (that inhibit dihydrofolate reductase such as methotrexate).

Neural tube development of the fetus is critically dependant on folic acid. Women considering getting pregnant should ensure intake of 0.4 mg/d. This amount must be consumed early because the neural tube develops very early in development (before most women know that they are pregnant). Supplementation should not exceed 1 mg/d to avoid complicating a vitamin B12 deficiency.

Toxicity: Masks vitamin B12 deficiency (mainly in elderly)

This diagram shows the chain of events requiring Folic Acid. It also shows how bacteria synthesize folic acid and how medications such as sulfa abx and dihydrofolate reductase inhibitors inhibit folate synthesis.

VITAMIN B12 (PYRIDOXINE)

VITAMIN B12 (COBALAMIN)

In contrast to the other water soluble vitamins, cobalamin is stored in the body (~4-5 mg)

Good sources: This vitamin is not found in plants! It is synthesized only by microorganisms. Animals obtain cobalamin from intestinal flora or by eating the meats of other animals. Especially liver, whole milk, eggs, oysters, fresh shrimp, pork, and chicken.

DRI: 1.8-2.4 mg/d

Functions: Essential for 2 enzymatic reactions: synthesis of methionine and isomerization of methylmalonyl CoA that arises from odd fatty acid chains. Cobalamin converts some forms of THF to the active form. If cobalamin is deficient, the inactive forms build up and cannot be converted. Therefore, cobalamin deficiency can resemble folic acid deficiency and vice versa.

Deficiencies: Pernicious anemia. Deficiency is most often due to an inability to absorb the vitamin rather than an inadequate amount in the diet. This disease is often due to an autoimmune attack of the gastric parietal cells which produce intrinsic factor. Intrinsic factor binds to cobalamin and forms a complex that is absorbable. Without intrinsic factor, cobalamin is not absorbed. Vitamin B12 deficiency can also lead to CNS symptoms. Folic acid supplementation can correct the anemia associated with vitamin B12 deficiency but not the CNS effects. Make sure you know which is deficient!

Toxicity: None known
Vitamin C (Ascorbic Acid)

VITAMIN C

Good sources: Rapid growing veggies (cabbage, broccoli, asparagus, brussel sprouts), citrus fruits, and raw potatoes

RDA: 60 mg/d. There is an active pool in the body of about 1500 mg. There is a limit to Vit C absorption. If you consume 100 mg then 100% is absorbed. However, if you consume 12,000 mg then only 16% is absorbed.

Functions: Antioxidant (see oxidative damage); involved in numerous catalyst reactions; collagen synthesis; increases iron absorption; enhances immune function. Vitamin C is a co-enzyme in hydroxylation reactions. If you will recall, proline and lysine are hydroxylated to form collagen. Hence the role of vitamin C in collagen synthesis.

Deficiencies: Scurvy: sore, spongy gums; loose teeth; fragile blood vessels; swollen joints; and anemia

Toxicity:

  • Diarrhea- you know, the runs…
  • Kidney stones- vitamin C is metabolized to oxylate which binds with calcium. They pack together to form a stone. If you increase magnesium, it binds with oxylate (instead of calcium) which is water soluble and can be eliminated.
  • Dependency- If you consume large quantities, you can become dependent on that level of vitamin C. For example, if you consume 1 gram per day and then decrease consumption to 100 mg per day, you can have some withdrawl symptoms despite the fact that your intake is above the RDA.
  • Rebound scurvy- along the same lines as described above but the symptoms are those of scurvy

Vitamin D

VITAMIN D

Interest in the importance of Vitamin D is increasing. It was on the Top 10 Medical Breakthroughs for Time Magazine in 2007. It was also featured in a 2008 issue of Discover Magazine entitled Can Vitamin D Save Your Life?

This is one of the ones that can be synthesized in the body. It is synthesized in the skin due to sunlight exposure. It is actually a group of sterols with hormone-like activities.

1,25-dihydroxycholecalciferol is the active form.

Functions: It is essential for bone health!

It regulates serum calcium and phosphorus levels. Metabolizes calcium and phosphorus (bone and teeth formation). In the intestine, it increases calcium and phosphorus absorption. There is a demineralization of bone if there is not enough vitamin D. In the kidneys it regulates calcium and phosphorus levels.

Good sources:

You have 2 choices for vitamin D intake: Sun exposure and Diet

Dietary: There are two forms of vitamin D that you can obtain in the diet:

  • Ergocalciferol (vitamin D2) which is found in plants. When your Vitamin D levels are low, this is the one we typically prescribe.
  • Cholecalciferol (vitamin D3) which is found in animal sources (egg yolks, organ meats, fortified milk, and cod liver oil).

Fatty fishes (salmon, mackrel, herring, etc) have about 500-1000IU. Also it has to be wild caught. Farm-raised salmon has next to no Vitamin D.

Sun exposure: 7-dehydrocholesterol is an intermediate in the natural synthesis of cholesterol. The skin can convert this molecule to cholecalciferol if exposed to UV light.

90-95% of our vitamin D comes from sun exposure.

How much sun exposure do we need? If you get enough sun exposure to cause a light pinkness of the skin (arms & legs) 24 hours later, it is equivalent to taking about 20,000IU of vitamin D orally. Black people tend to be more vitamin D deficient because they are much more resistant to UV exposure.

You cannot become vitamin D toxic from sun exposure.

Both of the dietary sources are inactive forms and must be converted to 1,25-dihydroxycholecalciferol to be active. You can see the mechanism for this process in the picture below.

DRI: 5 mg or 200 IU

How much should we really take?

  •  1600IU per day -70% of pregnant women who took 600 IU per day. It is recommended that pregnant women take 1000IU on top of their pre-natal vitamins and drinking 2 glasses of milk per day.
  • Obese – 2-3x more than normal weight people
  • A minimum of 1000IU per day for most people

If your Vitamin D level is low, we treat it with high doses of Ergocalciferol (Vitamin D2) according to the following schedule:

  • <18 – Ergocalciferol 50,000IU 3 times per week for 8 weeks
  • 18-25 – Ergocalciferol 50,000IU 2 times per week for 8 weeks
  • 25-30 – Ergocalciferol 50,000IU 1 time per week for 8 weeks

You should have a Vitamin D level checked after these 8 weeks. If it is normal you should probably take 50,000IU every other week from that point on.

Deficiency:

Testing: we check a 25-hydroxy vitamin D. This is the inactive form as D2 or D3. We want this level above 30 but less than 100 (to be on the safe side).

  • Ricketts (bones are soft and pliable).
  • osteomalacia (bone demineralization) – generalized bone pain
  • poor growth
  • muscle twitching.
  • Vitamin D deficiency has been related to numerous other health problems such as
  • cancer (breast, colon, prostate) a lot of this evidence is association, not necessarily cause
  • cardiovascular disease
  • all cause mortality
  • multiple sclerosis

Toxicity: Must be chronic to be toxic. Toxicity is difficult to achieve. It takes very high doses over long periods of time. However, it is extremely toxic (the most toxic of all the vitamins!!). It calcifies soft tissue which can cause aortic rupture. It can also cause kidney damage. High doses (100,000 IU for weeks to months) can cause loss of appetite, nausea, thirst, and stupor.
Vitamin E

VITAMIN E

Actually, there are 8 naturally occuring tocopherals. α-tocopheral is the most active.

Good sources: Vegetable oils, margarine, wheat germ, nuts, dark green veggies, and whole grains. Liver and eggs contain moderate amounts.

RDA: 10 mg for males and 8 mg for females. However, as your intake of polyunsaturated fatty acids goes up so does the requirement for vitamin E. Remember, the RDA is set to 20% above the level that would cause deficiency symptoms. I think most experts would recommend at least 400 mg/d.

Functions: The main function is as an antioxidant (see oxidative damage). It maintains cell membranes and helps with RBC formation.

Deficiency: Almost exclusively limited to premature infants. When it is seen in adults it is usually due to problems with lipid absorption. Symptoms include RBC sensitivity to peroxides and damaged cellular membranes. This is probably due to vitamin E’s antioxidant protective role. You gotta have this stuff!

Toxicity: Almost impossible! No toxicity has been noted even at doses 10,000 times the RDA.
Vitamin K

VITAMIN K

A family of compounds found in plants, fish oils, and meats. A couple of diagrams that I think are important are at the bottom of the page.

Good sources: Green leafy veggies, fruit (esp. strawberries), spinach, cabbage, egg yolks, fish, liver, and dairy products. A large portion of vitamin K is also produced by flora in the intestines. In fact, prolonged treatment with wide-spectrum antibiotics can decrease blood coagulation. Now you know how this is possible. Some 2nd generation cephalosporins (cefoperazone, cefamandole, and moxalactam) can also cause this effect (probably due to a warfarin like mechanism).

RDA: No RDA has been set but 70-40 mg per day appears to be adequate.

Functions: Formation of blood clotting agents (prothrombin, factor IX). It can be re-used.

  • Formation of g-carboxyglutamate- The proteins for prothrombin and the clotting factors VII, IX, and X are formed as inactive precursors. Carboxylation of glutamate residues forms a mature clotting factor that contains g-carboxyglutamate (Gla). This carboxylation is dependant upon vitamin K. Dicumarol, a naturally occuring anti-coagulant found in spoilt sweet clover, and warfarin, a synthetic analog of vitamin K, both inhibit the formation of Gla.
  • Interaction of prothrombin with platelets- The Gla residues contain carboxyl groups (which are negatively charged). These carboxyl groups attract calcium ions (positively charged) which are then able to interact with the phospholipid membranes of platelets.
  • Rold of g-carboxyglutamate residues in other proteins- These Gla residues are also present in other proteins but the role of vitamin K in their synthesis is not clear.

Deficiency: Hemorrhage. Infants are given an injection of vitamin K at birth. Their intestines are sterile and they cannot have vitamin K produced (hence the injection). However, deficiency is rare in the adult because of the large amount synthesized by intestinal bacteria.

Toxicity: Toxic to the membrane of RBC’s at high doses. Long-term, high-dose administration can cause jaundice and hemolytic anemia.