One-Six-Twelve Forte

VITAMINS B1 + B6 + B12

Film-Coated Tablet

VITAMIN

Category:

Description

DESCRIPTION

Formulation

Each One-Six-Twelve tablet contains:

Vitamin B1 (thiamine)……………..100 mg

Vitamin B6 (pyridoxine) …………. 200 mg

Vitamin B12 (cyanocobalamin)…. 200 mcg

MECHANISM OF ACTION

Vitamins are organic substances required by the body in small amounts for various metabolic process3es involving growth and bone development, reproduction, tissue maintenance and muscular integrity among others. Although vitamins occur naturally in various foods, adequate nutrition is not always attainable for all.

CHEMISTRY AND ASSAY

Thiamine was the first member of the vitamin B complex to be identified. Thiamine is a generic term applied to all substances possessing vitamin B1 activity, regardless of the anion attached to the molecule.

Thiamine compounds are usually readily soluble in water or in alcohol but insoluble in fat solvents. They are stable in acid solution and may be heated without decomposition but are unstable in neutral or alkaline solution. At neutral or alkaline pH, splitting occurs at the methylene bridge upon heating in the presence of moisture. Splitting of the molecule takes place quantitatively in the presence of bisulfate ions, a reaction that is mad use of in preparing dietary constituents free of thiamine for bioassay purposes (Remington, 20th edition).

Pyridoxine (Vitamin B6) does not denote a single substance but is rather a collective term for a group of naturally occurring pyridines that are metabolically and functionally interrelated, namely, pyridoxine, pyridoxal and pyridoxamine. They are interconvertible in vivo in their phosphorylated form. There is no information on the relative biological activity of the three compounds in humans, and since pyridoxine is the most stable, it probably contributes the most vitamin activity to the diet (Remington, 20th edition).

Pyridoxine as the free base has a bitter taste and is readily soluble in water, alcohol or acetone. It crystallizes as the hydrochloride and is prepared in this form for commercial use. Pyridoxine is one of the more stable vitamins and in the alcohol form withstands heating in acid or alkaline solution. Under most conditions of processing and storage of foods and pharmaceutical preparations, the vitamin is retained well. (Remington, 20th edition).

Cyanocobalamin (B12), was isolated from liver fractions in crystalline form. It is a complex water-soluble compound that crystallizes as small red needles that have a specific rotation in dilute aqueous solution of -59 degrees Centigrade. (Remington, 20th edition)

Commercially, vitamin B12 is obtained from fermentation by Streptomyces griseus. Vitamin B12 is one of the most active biological factors known; its activity for bacteria is measured in terms of millimicrograms. Because of this sensitivity of some bacteria to such low levels of the vitamin and the fact that foods contain exceptionally low concentrations of the vitamin, microbiological methods are widely used. (Remington, 20th edition)

PHARMACOLOGY

Vitamins can be divided into two types:

  1. Water soluble vitamins
  2. Fat soluble vitamins

The water soluble vitamins, e.g. Vitamin B complex, etc. are used readily and metabolized to be rapidly excreted in the urine. They are not stored in the body. This is why they are needed on a daily basis in order for the body to maintain healthy levels.

The fat soluble vitamins, e.g. Vitamins A,D,E and K have an accumulative effect and are stored in the body which can be potentially dangerous.

Thiamine

Thiamine (Vitamin B1) is involved in energy-yielding metabolic systems, especially those involved in carbohydrate metabolism. It is an essential coenzyme that combines with adenosine triphosphate (ATP) to form a coenzyme, thiamine pyrophosphate (thiamine diphosphate, cocarboxylase), which are involved in oxidative decarboxylation.

It is essential for carbohydrate metabolism, energy release and healthy heart, brain, nervous system and muscle function. It is utilized in the body to synthesize neurotransmitters, including Acetylcholine and gamma-aminobutyric acid (GABA).

Absorption of the usual dietary amounts of thiamine from the gastrointestinal tract occurs by Na+ dependent active transport; at higher concentrations, passive diffusion is also significant.

Thiamine is a vitamin with antioxidant, erythropoietic, cognition-and mood-modulatory, antiatherosclerotic, putative ergogenic, and detoxification properties.

Thiamine plays a key role in intracellular glucose metabolism and it is thought that thiamine inhibits the effect of glucose and insulin on arterial smooth muscle cell proliferation. Inhibition of endothelial cell proliferation may also promote atherosclerosis. Endothelial cells in culture have been found to have a decreased proliferative rate and delayed migration in response to hyperglycemic conditions. Thiamine has been shown to inhibit this effect of glucose on endothelial cells.

Thiamine is also essential in helping the body convert carbohydrates and fat into energy. It is needed for normal growth and development and helps to maintain proper functioning of the heart and the nervous and digestive systems. Thiamine cannot be stored in the body; however, once absorbed, the vitamin is concentrated in muscle tissue.

Signs of deficiency in this vitamin include extreme weakness (such as beriberi in developing countries with poor diet), depression, numbness and tingling in the extremeties, poor memory, headache and disturbed sleep.

Pyridoxine

Vitamin B6 (pyridoxine) is a water-soluble vitamin used in the prophylaxis and treatment of vitamin B6 deficiency and peripheral neuropathy in those receiving isoniazid (isonicotinic acid hydrazide, INH). Vitamin B6 has been found to lower systolic and diastolic blood pressure in a small group of subjects with essential hypertension.

A study showed that pyridoxine hydrochloride inhibits ADP- or epinephrine-induced platelet aggregation and lowers total cholesterol levels and increase HDL-cholesterol levels, again in a small group of subjects. Vitamin B6, in the form of pyridoxal 5′-phosphate, was found to protect vascular endothelial cells in culture from injury by activated platelets. Endothelial injury and dysfunction are critical initiating events in the pathogenesis of atherosclerosis. Human studies have demonstrated that vitamin B6 deficiency affects cellular and humoral responses of the immune system. Vitamin B6 deficiency results in altered lymphocyte differentiation and maturation, reduced delayed-type hypersensitivity (DTH) responses, impaired antibody production, decreased lymphocyte proliferation and decreased interleukin (IL)-2 production, among other immunologic activities.

Pyridoxine is a precursor to pyridoxal, which functions in the metabolism of protein, carbohydrates, and fats; pyridoxal also aids in the release of liver and muscle – stored glycogen and in the synthesis of GABA (within CNS) and heme. Studies have proved that proper amount of B6 relieves vomiting or nausea in women during pregnancy. The recommended dietary allowances for vitamin B6 ranges from 1.3 to 2 mg, which further depends on various factors like age, sex etc. Its deficiency may result in skin disorders, nausea, anemia, smooth tongue, dizziness, convulsions, and kidney stones. Signs of deficiency include irritability and nervousness, flaky skin around the eyes, nose and mouth, sore tongue.

Together with Vitamin B12, Vitamin B6 aids in keeping homocysteine levels low. Elevated homocysteine levels are associated with neurodegeneration and heart disease.

Cyanocobalamin

Cyanocobalamin (Vitamin B12) is a water-soluble organometallic compound with a trivalent cobalt ion bound inside a corrin ring. It is a dietary essential for man. Deficiency in this vitamin results in defective synthesis of DNA in any cell that attempts chromosomal replication and division.

It contributes towards healthy nervous and cardiovascular systems, formation of red blood cells and bone marrow, production of genetic material and metabolism of fats, proteins and carbohydrates.

Low levels of vitamin B12 are commonly found among dementia patients. Deficiency in this vitamin is likewise seen in patients with pernicious anemia in whom the specialized stomach cells required for Vitamin B12 absorption are destroyed by an autoimmune response.

Signs of deficiency in this vitamin include exhaustion, anemia, pallor, pins and needles in hands and feet, irritability, depression and shortness of breath on exertion.

Vitamin B12 is required in the process of S-adenosylmethionine (SAM-e) synthesis, the biologically active form of the essential amino acid methionine. Additionally, vitamin B12 supplementation is thought to decrease levels of the neurotoxin, homocysteine.

It is a cofactor in two enzymes that are fundamental in facilitating growth. As methylcobalamin, vitamin B12 is the cofactor of methionine synthase and, as adenosylcobalamin, is the cofactor in methylmalonyl-CoA mutase. Both reactions are involved in promoting the rapid growth and proliferation of the cells of the bone marrow.

The development of vitamin B12 deficiency during adult life is not usually the result of a deficient diet; rather, it reflects some defect in gastrointestinal absorption. Classical Addisonian pernicious anemia is caused by a loss of gastric parietal-cell function and production of the glycoprotein gastric intrinsic factor. The parietal cells may fail because the presence of cytotoxic autoantibodies.

Dietary vitamin B12, in the presence of gastric acid and pancreatic proteases, is released from a salivary binding protein and is immediately bound to intrinsic factor, a glycoprotein.

Any of a number of intestinal diseases or defects can interfere with the absorption of the intrinsic factor-B12 complex. The combination of gastric achlorhydria and decreased secretion of intrinsic factor secondary to gastric atrophy or gastric surgery is a common cause of vitamin B12 deficiency in adults. The requirement for pancreatic proteases to release vitamin B12 from binding proteins, such that it can then bind to intrinsic factor, explains the malabsorption of the vitamin in pancreatic disorders.

Once absorbed, vitamin B12 binds to transcobalamin II, a plasma beta-globulin, for transport to tissues. Vitamin B12 bound to transcobalamin II is rapidly cleared from plasma and is preferentially distributed to hepatic parenchymal cells.

TOXICOLOGY

Toxicity following acute overdosage is unlikely unless a massive dose has been ingested. Large overdoses of water soluble vitamins are readily excreted in the urine hence, are likely to produce no acute toxic symptoms.

PHARMACOKINETICS

Small amounts of thiamine are well absorbed from the GI tract after oral doses, but the absorption of doses larger that about 5 mg is limited.  It is widely distributed to most body tissues and appears in breast milk. Thiamine is not stored to any appreciable extent in the body and excess amounts of the body’s requirements are excreted in the urine either unchanged or as metabolites.

Pyridoxine is stored mainly in the liver where there is oxidation to 4-pyridoxic acid and other inactive metabolites which are excreted in the urine. It crosses the placenta and is distributed into breast milk.

Vitamin B12 substances bind to intrinsic factor, a glycoprotein secreted by the gastric mucosa and then actively absorbed from the gastrointestinal tract. Absorption can also occur by means of passive diffusion wherein little of the vitamin remains in food once absorbed in this manner. Cyanocobalamin is extensively bound to plasma proteins. It is stored in the liver, excreted in bile and undergoes extensive enterohepatic recycling; part of a dose is excreted in the urine, most of it within the first 8 hours. However, urinary excretion only accounts a small fraction in the reduction of the total body stores acquired by dietary means. Vitamin B12 diffuses across the placenta and also appears in breast milk.

INDICATIONS

Thiamine is especially useful for those who smoke or drink heavily, do strenuous physical work, with a diet high in sugar and refined carbohydrates, heart probles, on a growth spurt or under a lot of stress.

Polyneuritis (dysfunctioning of the nervous system) or beriberi is the frank disease associated with thiamine deficiency in humans. Peripheral neuritis is a pathological condition of the nerves of the extremities; usually both legs are affected and sometimes the arms as well. The symptoms include loss of sensation, muscle weakness and paralysis. In beriberi this condition also is associated with edema and abnormal electrocardiogram patterns. Symptoms of thiamine deficiency have been observed among chronic alcoholics, who use alcohol in place of food as a source of energy. Deficiency also occurs in cases of chronic diarrhea, in which absorption is interfered with over a period of time and during pregnancy complicated with anorexia and nausea. (Remington, 20th edition)

Cardiovascular disease of nutritional origin is observed in chronic alcoholics, pregnant women, persons with gastrointestinal disorders and those whose diet is deficient for other reasons. When the diagnosis of cardiovascular disease due to thiamine deficiency has been correctly made, the response to the administration of thiamine is striking. One of the pathognomonic features of the syndrome is an increased blood flow due to arteriolar dilatation within a few hours after the administration of thiamine, the cardiac output is reduced and the utilization of oxygen begins to return to normal. If edema is present and due to myocardial insufficiency, diuresis results after proper therapy. (Goodman and Gilman’s)

Although there is no doubt that pyridoxine is essential in human nutrition, the clinical syndrome of simple pyridoxine deficiency is rare. Nevertheless, it may be presumed that an individual with a deficiency of other members of the B complex may also have a deficiency of pyridoxine. Therefore, pyridoxine should be a component of therapy for individuals suffering from a deficiency of other members of the B complex. On the basis that pyridoxine is essential in human nutrition; it is incorporated into many multivitamin preparations for prophylactic use. It has been pointed out that 30% or more of alcoholics have biochemically demonstrable deficiency of vitamin B6.

Vitamin B6 is useful for those experience morning sickness, PMS, insomnia and mild forms of anxiety and depression. It is likewise recommended for women taking the contraceptive pill or on long-term HRT since these can lead to the depletion of vitamin B6.

Vitamin B6 in the form of pyridoxal phosphate or pyridoxamine phosphate functions in carbohydrate, fat and protein metabolism; its major functions are most closely related to protein and amino acid metabolism. (Remington, 20th edition)

Vitamin B12 is indicated for those suffering from anemia, fatigue, digestive problems, mental or nervous problems. Vegans and vegetarians can become deficient in vitamin B12 since it is mainly found in animal produce.

Vitamin B12 is essential for the normal functioning of all cells, but particularly for cells of the bone marrow, the nervous system and the GI tract. It appears to facilitate reduction reactions and participate in the transfer of methyl groups. Evidence exists that vitamin B12 is involved in protein, carbohydrate and fat metabolism. (Remington, 20th edition)

Vitamin B12 is a requisite for normal blood formation and certain macrocytic anemias respond to its administration. Vitamin B12 deficiency is recognized clinically by its impact on both the hematopoietic and the nervous systems. The sensitivity of the hematopoietic system relates to its high rate of turnover of cells. (Goodman and Gilman’s)

As a result of an inadequate supply of vitamin B12, DNA replication becomes highly abnormal. This result in the production of morphologically abnormal cells or death of cells during maturation, a phenomenon referred to as ineffective hematopoiesis.

Vitamin B12 deficiency can result in irreversible damage to the nervous system. Progressive swelling of myelinated neurons, demyelination and cell death are seen in the spinal column and cerebral cortex. This causes a wide range of neurological signs and symptoms, including paresthesias of the hands and feet, diminutions of vibration and position senses with resultant unsteadiness, decreased deep-tendon reflexes, and, in the later stages, loss of memory, confusion, moodiness and even a loss of central vision.

Since the neurological damage can be dissociated from the changes in the hematopoietic system, vitamin B12 deficiency must be considered as a possibility in elderly patients with dementia and psychiatric disorders, even if they are not anemic.

DOSAGE AND ADMINISTRATION

One-Six-Twelve Forte may be taken one to two tablets 3 times daily or as prescribed by the physician.

CONTRAINDICATIONS

One-Six-Twelve Forte should not be given to patients with hypersensitivity to any component in the formulation (may contain inactive ingredients that can cause allergic reactions or other problems).

DRUG INTERACTIONS

One-Six-Twelv Forte should not be used on patients on levodopa monotherapy. Vitamin B6 accelerates peripheral metabolism of levodopa to dopamine, reducing the availability of dope for conversion to dopamine, and impairing the therapeutic activity of levodopa. As little as 5 mg pyroxidine daily can decrease the efficacy of levodopa in the treatment of parkinsonism. Therfore, ONE-SIX-TWELVE FORTE tablet is not recommended for patients taking levodopa alone.

ADVERSE EFFECTS

Allergic and idiosyncratic reactions are possible at low levels.

STORAGE

Store at a temperature not exceeding 30oC. Protect from light.

KEEP OUT OF REACH OF CHILDREN.

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