International Nutrition Consultant Association

Vitamin B₁-This is one of the 9 water-soluble vitamins and of course, one of the B vitamins. Vitamin B₁ is also known as thiamine. Thiamin functions as a cofactor in the oxidative decarboxylation of alpha-keto acids. For example, alpha-ketoglutarate, is converted to succinyl CoA by the enzyme alpha-ketoglutarate dehydrogenase. This enzyme complex requires vitamin B₁as a cofactor, as well as lipoic acid, NAD⁺, FAD, and CoA.

Before vitamin B₁ (thiamine) can be used as a cofactor for this enzyme, it must be converted to the active form, which we call thiamine pyrophosphate (TPP). Thiamine is converted into TPP by addition of a pyrophosphate group from ATP to thiamine. ATP is a molecule that supplies phosphates and energy for many reactions in the body. ATP is also used in reactions such as those while contracting muscle tissue, and many others. The active form of thiamine is also used as a cofactor for the enzyme alpha-transketolase. Alpha-transketolase forms and degrades alpha-ketols in the pentose phosphate pathway, which is a series of reactions supplying intermediates for nucleotide synthesis and glycolysis. These reactions supply parts for genetic material in cells, and help to utilise carbohydrates. Thiamine is needed for these reactions.

Thiamine can be found in pork, organ meats, legumes, nuts, and whole grain or enriched cereals and breads. The outer layer of seeds are rich in thiamine. This is the premise for whole wheat bread being more nutritious for the consumer, versus white bread, which is prepared from milled grain and is low in thiamine.

The amount of thiamine required in the diet is proportional to the amount of caloric intake. 0.5 mg (half of a milligram) is required for each 1000 kcal in the diet. For the average male who consumes 3000 kcal/day, this equates to 1.5 mg of thiamine per day. The typical UK and US diets provide less than 0.8 mg.day, thus we seem to be shortchanging ourselves a bit when it comes to thiamine. Small supplemental doses of thiamine can be taken to provide the RDA. And of course, some personal diets, or from various cultural diets can supply the necessary amounts.

In the US and UK, thiamine deficiency is observed primarily in chronic alcoholism. This is most likely due to dietary insufficiency (not eating properly) and impaired intestinal absorption of thiamine. A percentage of those suffering from chronic alcoholism develop Wernicke-Korsakoff syndrome, a thiamine deficiency state characterized by amnesia (memory loss), apathy, and a rhythmical back and forth motion of the eyes. If the individual is not quickly treated with thiamine, coma, irreversible brain damage and death can result.

Beri-Beri, which comes from Singhalese, meaning "I cannot", signifies that the person is too ill to do virtually anything. Beri-Beri is a severe thiamine deficiency observed in areas where polished rice composes the major portion of the diet. Infantile Beri-Beri is characterized by tachycardia (rapid heart rate), vomiting, convulsions, and death, if not treated. Infantile Beri-Beri has a quick onset in nursing infants where the mothers are deficient in thiamine. The mother will use most of the already low source of thiamine, and the infant will get barely enough to survive. Adult Beri-Beri is characterized by dry skin, irritability, impaired cognition and progressive paralysis.

Vitamin B₂-Also known as riboflavin, this water- soluble vitamin is also known as a flavin. A flavin is any compound that happens to contain in its structure, what is known as an isoalloxazine molecule. It is not essential to know this, but rather more importantly in regards to function what the vitamin does for us. This flavin functions as a component of FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide). FMN abd FAD are known as flavoproteins. Tlavoproteins are simply proteins that contain the flavin molecule as described above. These flavoproteins act as enzymes to speed up reactions in our body. Otherwise, chemical reactions in our body would take infinitely longer and this would affect our health. For these enzymes to work efficiently, some of them need riboflavin. This flavin helps the enzyme to work properly. With riboflavin dificiencies, the enzyme cannot work properly, if at all. This can obviously have an impact on our health, since riboflavin dependent enzymes perform functions such as the metabolism (oxidation) of carbohydrates that we use for energy. FAD and FMN function as electron carriers in oxidation-reduction reactions. Riboflavin kinase is an enzyme that catalyzes the addition of phosphate to riboflavin to form FMN, a cofactor for electron transfer reactions.

Basically, riboflavin is converted to its active forms, which are FMN and FAD, as discussed above. Once the active forms of riboflavin (FAD, FMN) are produced, they can reversibly bind with hydrogen (H), thus forming FADH₂ and FMNH₂. FADH₂ and FMNH₂ functions in metabolic pathways, essential to survival. Coenzyme Q can accept hydrogens from FADH₂ and FMNH₂ during the reactions from fatty acid degradation and other pathways.

Like thiamine the amount of riboflavin required depends on the caloric intake of the individual. 0.6 mg (milligrams) are required for every 1000 kcal of dietary intake. For the average male, with an intake of 3000 kcal, this is equivalent to 1.8 mg of riboflavin per day. A minimum of 1.2 mg/day of riboflavin is recommendd for adults.

Deficiency of riboflavin is referred to as ariboflavinosis, and is characerized by dermatitis, cheilosis (cracks or fissuring at the corners of the mouth), and glossitis (a smooth and purple tongue). Riboflavin deficincies normally are not observed on their own, but usually in conjunction with other vitamin deficiencies (eg., economically impoverished areas, starvation). However, araboflavinosis can be observed in select cases, such as in practicing incorrect vegetarianism, those suffering from alcoholism, chronic infections, advanced cancer and other debilitating diseases.

Riboflavin is added to foods for reasons of fortification and colouring. For example, fortifying cereals, drinks, slimming and diet supplements, as well as other foods with riboflavin helps in ensuring proper amounts of riboflavin in our diet. Riboflavin is also used in a small percentage of foods as a colouring. This is acceptable, considering that it is a vitamin.

Riboflavin is a water-soluble vitamin, required as a cofactor for several enzymes. Riboflavin can be obtained naturally from milk, eggs, liver and leafy vegetables. In processed or manufactured foods, howver, riboflavin may be added for the purposes of fortifying the product (add vitamin content to it, such as in cereals, or to act as a food colouring (eg., in candies or sweets). Riboflavin added in processed foods can be synthesized chemically, or by bacteria. Suitable, and harmless bacteria such as Bacillus subtillus are genetically altered to "overproduce" riboflavin. The riboflavin is then extracted from the broth, purified and sold to food manufacturers. All is fine and well so far, because no matter how riboflavin is produced (whether in nature or in the laboratory), it is chemically identical.

The problem arises when during the synthesis of riboflavin, small amounts of other chemicals which are similar to riboflavin, but not exact. This presents a particular problem, because with subtle differences in a molecule such as riboflavin, this can have a large impact on our health. I am looking into the exact percentages of allowable impurities contained in industry grade riboflavin. Of course, it is well-known that animal feed grade was customary to have around 96% purity and the purity for human use was around 98%. I'm a bit concerned about the animal feed purity, since we rear animals to be eaten by humans anyway. Riboflavin (the vitamin) is required: we need it to live. However the by-products of industrial synthesis may present a potential hazard. Why is this?

Some of the by-products of riboflavin production are lumiflavin, lumichrome and other by-products. Other by-products in very small amounts may also be produced depending on the method of production and processing techniques used. For example, during bacterial fermentation to obtain riboflavin, acids can be used to ensure bacterial DNA are destroyed. This can affect the riboflavin and cause other by-products to form (even with the DNA substrates). The point is, some of these by-products cause changes in the blood parameters, such as increased thrombocyte levels, and changes in haemoglobin levels. Organ weights are also affected. Keep in mind that these studies usually use higher amounts. However, there is clearly a definite affect from these impurities. Those with blood dyscrasias should take a little extra notice, considering these minor factors sometimes can be the proverbial "straw that breaks the camel's back" when it comes to monitoring lifestyle.

The solution-I would rather obtain natural riboflavin, which you can get from milk, liver, eggs, and leafy vegetables. Note that with consuming meats, you can always find out if the animals are grain fed, etc., and what type of grain is used. Is it treated with synthetic riboflavin. Sometimes researching these aspects of nutrition seem daunting.

Prothrombin and the blood clotting factors are proteins which are manufactured in the liver. These proteins are intentionally manufactured "incomplete". If they were manufactured completely, unwanted clotting could occur. When "activity" is needed (eg., during a bleeding episode, due to cutting of the skin, etc.), prothrombin is made "active" by the carboxylation (adding CO₂) of its glutamic acid residues. Glutamic acid (abbrev., Gla) is one of the 20 amino acids that the human utilises, reviewed in proteins. The carboxylation of glutamic acid residues is vitamin K-dependant. The overall reaction requires prothrombin, the hydroquinone form of vitamin K, O₂ and CO₂.

In all probability, there are other important functions of vitamin K that we have not yet elucidated. Glutamic acid residues are found in proteins unrelated to the clotting cascade, and these may undergo reactions with hydroquinone (vitamin K) as well. Therefore, keep in mind that vitamin K, as with other vitamins most likely serve many other purposes, as we shall verify with more research. In any event, vitamin K is required in the clotting cascade, and this is vital to survival. Clotting not only serves to prevent blood loss when we superficially injure ourselves. Clotting is a process that occurs constantly in all areas of the body as a result of microscopic insults, such as minor internal day to day traumas, wear and tear, and even to stop internal bleeding from undetected genetic anomalies of the circulatory system. Deficiency of vitamin K can lead to bleeding tendencies, increased clotting times, and other anomalies.

Good sources of vitamin K are spinach, cauliflower, cabbage (uuuggh !!), egg yolk, and liver. Normal bacterial flora residing in the gut also synthesize vitamin K for us! Amounts vary though, considering the type of bacterial populations differ in individuals. Therefore, although it is beneficial that bacteria help us with some vitamin K production, we should not rely on it entirely, since amounts vary per individual. Rather we should rely on a proper diet to ensure adequate amounts of each nutrient.

There is no established RDA for vitamin K. However, 70 to 140 micrograms/day is the recommendation. The lower level of 70 micrograms assumes bacterial synthesis from gut bacteria, and the upper limit recommendation of 140 micrograms assumes no bacterial contribution. Again, this is controversial, and a little extra vitamin K is not harmful.

Vitamin K deficiency in the adult is rare. This is because of its wide distribution in food sources and the varying contribution from bacteria. It can be observed in areas of poverty and in malnutrition. Deficiency is characterized by a prolonged clotting time, and this can sometimes be seen in newborns of any economic background. This is why infants are given an injection of vitamin K, as discussed above.

Administration of large doses of vitamin K can cause haemolytic anaemia, hyperbilirubinaemia [increased amounts of bilirubin (breakdown product of haemoglobin from the red blood cell) in the blood] and jaundice of the newborn due to toxic effects imposed on the membrane of the red blood cells. Newborns can also develop an enlarged liver. In the adult, excessive doses can cause a decrease in liver function and hypoprothrombinaemia (decreased prothrombin synthesis).

Total dose should not exceed 3 mg (milligrams) of menadiol or 1 mg of menadione. With an increase of companies selling injectable vitamins, extreme caution should be taken. With this "in vogue" trend increasing in the hopes of the best health, there are certain countries which allow injectable vitamins to be purchased without a doctors advice or prescription. There is really no place for injectable vitamins, with exception to newborns (discussed above), or with a medical condition (eg., vitamin B₁₂ malabsorption). Along with the general risks of injecting, there are other dangers. For example, regarding vitamin K, IV (intravenous) administration has caused deaths at injection rates greater than 1 mg per minute (in other words, injecting the load in too quickly). It is always best obtaining nutrients through diet, unless an existing medical condition dictates otherwise.

Vitamin B₆- A collective term for a group of water-soluble substances which include pyridoxine, pyridoxal and pyridoxamine. Pyridoxine, pyridoxal and pyridoxamine are all derivatives of pyradine and differ only in the functional group attached to this molecule. Pyridoxine occurs primarily in plants in comparison to pyridoxal and pyridoxamine, which are obtained from animal derived food. Pyridoxine, pyridoxal and pyridoxamine can equally serve as precursors of the biologically active enzyme, pyridol phosphate. Pyridoxal phosphate serves as a coenzyme in a number of reactions, particularly those involving the metabolism of amino acids and in the breakdown of glycogen. For example, histamine can be made from the amino acid histidine, from a reaction that requires pyridoxal phosphate.

The amount of pyridoxine required increases with the intake of protein. Since pyridoxine is involved with the metabolism of amino acids and proteins are composed of amino acids, more of the vitamin is required as protein intake increases. The RDA of pyridoxine is 2.2 mg (milligrams) for the adult males and 2.0 mg for adult females. This is based on a daily protein consumption of 100g. In individuals who participate in activities such as weighlifting, where increased amounts of protein are required and consumed, the amount of pyridoxine required additionally increases.

Isoniazid, a drug used for the treatment of tuberculosis, can cause a vitamin B₆ deficiency. Isoniazid accomplishes this by forming an inactive derivative with pyridoxal phosphate, rendering the molecule useless. The action of levadopa, a drug used to treat parkinsonism, is antagonized by pyridoxine.

Vitamin B₁₂-Cyanocobalamin by definition, but can include any substituted cobalamin derivative with similar biological activity. Vitamin B₁₂ is a water-soluble haematopoietic (blood forming) vitamin. Cobalamin contains a corrin ring system with cobalt at the center. Commercial preparations of the vitamin are slightly modified and are known as cyanocobalamin (the cyano=cyanide). The coenzyme forms of the vitamin are 1) methylcobalamin, whereby the cyanide group is replaced by a methyl group and 2) 5^'-deoxyadenosylcobalamin, whereby the cyanide group is replaced with 5^'-deoxyadenosine.

To be absorbed by the intestine, vitamin B₁₂ must combine with intrinsic factor, which is produced in the stomach by gastric parietal cells. Vitamin B₁₂ is required for the growth and replication of all cells, including blood cells and is required for the proper functioning of the nervous system. Vitamin B₁₂ is also required for purine and pyrimidine (components of DNA) synthesis and is thus needed for DNA production.

Vitamin B₁₂ metabolism is connected with that of folic acid. In vitamin B₁₂ deficiency, reactions requiring this vitamin decrease, resulting in a subsequent decrease in reactions that convert folic acid to other derivatives. This essentially traps a portion of the folic acid pool to an unusable form. Therefore, sufficient amounts of vitamin B₁₂ must be present in order for folic acid to be utilised.

Good sources of vitamin B₁₂ are animal flesh, since this vitamin is not found in plant sources. Animals obtain their vitamin B₁₂ from their bacterial gut flora. The bacterial gut flora synthesize vitamin B₁₂ and small amounts of other vitamins. Therefore, we can obtain some of our vitamin B₁₂ from our own gut flora, and the rest from animal products, such as liver, whole milk, eggs, seafoods (oysters, shrimp), pork and chicken.

During the introduction to vitamins we discussed water-soluble and fat-soluble vitamins. Fat-soluble vitamins are stored to a large extent in the body in comparison to water-soluble vitamins, which are excreted more rapidly. Vitamin B₁₂ is a water-soluble vitamin. However, it is the exception to the rule regarding excretion from the body. Vitamin B₁₂ is stored in significant amounts (5 mg) in the body and depletion can take several years, depending on the individual and factors such as weight, activity, physiological state (eg., pregnancy, lactation).

Deficiencies are not normally from the diet, although vitamin B₁₂ can be rapidly depleted during starvation. Most deficiency states of vitamin B₁₂ are from intestinal complications, such as surgery. Gastrectomy, or removal of a portion of the stomach results in a lack of intrinsic factor which is required for vitamin B₁₂ to be absorbed by the ileum of the small intestine.

If the parietal cells fail for any other reason, the signs and symptoms of vitamin B₁₂ deficiency will develop once the stored supply of the vitamin is depleted. Any insult that damages the ileum as well, can cause a vitamin B₁₂ deficiency. Crohn's disease, and other inflammatory conditions that damage the ileum portion of the small intestine can cause vitamin B₁₂ deficiencies. Intestinal infections can also damage the intestinal wall, with the same outcome.

Cells with a high turnover rate such as the intestinal epithelium and haemopoietic cells of the bone marrow are the first to manifest the results of a vitamin B₁₂ deficiency. Since this vitamin is needed for proper purine and pyrimidine synthesis (for DNA), incorrect production occurs and is not packed correctly in cells, resulting in a larger than normal cell. This larger than normal cell is called a megaloblast, and is part of the condition known as megaloblastic anaemia, suffered by the individual lacking vitamin B₁₂.