Interaction of components of vitamin and mineral complexes and rational vitamin therapy

E. Shih

At present time vitamin complexes find more and more application for technologies of restorative medicine used for correction of functional conditions and increase of spare capacities of the organism affected by the hostilities of the environment.
Hypovitaminous background complicates the clinical course of the principal illness and reduces the efficiency of preventive measures. In view of this the patient’s treatment must include correction of existing polyvitamin deficiency and support optimal vitamin supply of the organism [12, 14, 17].
According to the results of statistical investigations, both doctors and their patients prefer vitamin and mineral complexes that contain maximum of components. Attempts to take the necessary daily dose of all the vitamins and minerals may considerably impede achievement of the final goal (prevention and/or treatment of certain symptoms). In many respects this can be explained by the interaction of components, which leads to full or partial loss of activity. Data from the literature and the results we have got confirm that there exist all the types of drug interaction as regards vitamins: pharmaceutical interaction – prior to administration of a medicine into the orgamism; pharmacokinetic – on different stages of pharmacokinetics; pharmacodynamic – on the stage of interaction with receptors [9, 10, 11].

Pharmaceutical interaction is a result of physicochemical reactions that take place among vitamins.
Thiamine hydrochloride is oxidated under the influence of riboflavin giving thiochrome with the formation of chloroflavin. Both may precipitate. Interaction between thiamine and riboflavin is intensified under the influence of nicotinamide. Nicotinamide practically establishes the sollubility of folic acid. Nicotinamide intensifies considerably the interaction between cyanocobalamin and thiamine. The solublity of riboflavin is also considerably intensified under the action nicotinamide. Adding nicotinamide to the solution of ascorbic acid and sodium riboflavin-u1092 increases photolysis of the latter. Ascorbic acid may to a certain extent prevent thiochrome precipitation, which may cause even greater formation of chloroflavin. [7].
Ascorbic acid reduces folic acid. Folic acid performs as an indispensavle cofactor for the transport of single-carbon links: for example, methyl groups delivered by methionine, an independent amino acid are necessary for the synthesis of different compounds – purine, pyrimidine, thimine, serine amino acid, choline, carnitine, creatinine, adrenaline and many others. In order to be able to perform its functions folic acid must be in its reduced tetrahydrofolate form, which state is provided and/or supported due to the presence of ascorbic acid. Riboflavin fosters anaerobic decomposition of ascorbic acid. Ascorbic acid in the form of solution reduces thiamine half life period [7].
Thiamine destroys folic acid. Ergocalciferol is subject to isomerization under the influence of ascorbic acid, thiamine and hydrochloride.

Chemical interactions of vitamins are more apparent in liquid medical forms as compared to solid ones.
There exist several methods of prevention of chemical interactions between vitamins: using two-chambered ampules for liquid medical forms, lyophilization, making powders or soluble granules for peroral preparations. Another option is to use multi-layer or laminated tablets as well as putting certain vitamins into coating or capsular membranes [4, 6, 11, 14]. Including microelements into vitamin products often leads to stability problems as far as some of them belong to heavy metals, which catalyze oxidative breakdown of some of the vitamins. In order to increase the stability of a medical form separate granules of vitamins and minerals are made and then united into a usual two-layer or laminated tablet. One of actual problems in pharmacy is development of ultimately stable multivitamin product and possibility to combine it with microelements.
However, changing production form of such preparation does not eliminate the probability of interaction of the components in the patient’s organism [2, 3]. We have compiled dozens of scientifically proved facts of negative and positive vitamin and mineral interaction during their assimilation in gastrointestinal tract (GT) and realization of physiological functions in internal environment of the organism.
Even minor content of ions of such elements as iron, cobalt, copper, magnesium, nickel, plumbum, cadmium produce catalytic effect on oxidative decomposition of many vitamins. The following vitamins belong to metal-sensitives: retinol and its ethers, riboflavin, pantothenic acid and its salts, pyridixine hydrochloride, acorbic acid and its salts, folic acid, cholecalciferol, ergocalciferol, rutin.
Large daily doses of vitamin C affect assimilation of vitamin B12 from food or food supplements. The shortage of vitamin E in the diet causes development of A hypovitaminosis. Vitamins B1, B2, B6 promote formation of niacin from tryptophan amino acid. Peroral use of polyvitamin complex leads to decrease in absorbtion of its constituent vitamins C, B6 as compared to monocomponent products. Besides, we know about negative effect of copper, iron and manganese on vitamin B12, copper on ascorbic acid, iron on vitamin E [4, 5, 7, 13, 21].
Out of 92 natural elements 81 were found in human organism. Our organism gets all the elements from its environment. 36 elements have clinical importance for the well-being of the human organism, 15 being “essential” – their reduction in the organism or their absence is subject to a certain clinical behaviour.
Most often vitamin and mineral complexes contain macroelements (calcium, magnesium, phosphoeus) and microelements (iron, copper, iodine, selenium, chromium, zinc and manganese). Their in teractions aren’t as easy as it seems: some compete others during absorbtion, some produce antagonistic effect on the level of receptors [1, 3, 4].
In order to estimate the real clinical importance of biologic synergism and antagonism it is necessary to take into account that “absorbtion competition” means that one element received with food and water in high concentrations interferes with absorbtion of another one (in low concentration). Upon passing the satge of gastrointestinal absorbtion into the homeostasis system the elements may interact between one another on biological level regardless of interaction during absorbtion. Competition for ligand-target may result both in synergism and antagonism judging by the final outcome of physiological effect.
Calcium competes for absorbtion with iron, copper, magnesium, plumbum; magnesium competes with calcium and plumbum; copper – with zinc, manganese, calcium and cadmium. Phosphates affect absorbtion of calcium, magnesium, copper and plumbum. Iron is a zinc antagonist, competes for absorbtion with cadmium, copper, plumbum, phosphates and zinc. Cadmium competes practically with all macro- and microelements normally included into complexes and performs as their antagonist. Zinc, copper, selenium and calcium impede cadmium absorbtion. On the level of receptors the interaction of these elements is antagonistic – excess of cadmium causes zinc, copper, selenium and calcium deficiency [4, 3].
Based on these data there arises a question of appropriateness of simultaneous intake of all the necessary elements in one tablet. Dividing the daily dose of necessary elements into several tablets, their intake during day following the time interval will allow to avoid adverse interactions and foster favourable effects.
As it has already been mentioned, at present time we have enough information to give reliable evidence for the existence of a number of synergic interactions of vitamins and macroelements, which makes it hardly possible to create vitamin and mineral complexes for efficient treatment of pathologies without their consideration. Understanding the mechanisms of such interaction allows a practicing doctor to choose a rational vitamin and mineral complex for prvention and/or treatment of certain pathologies in the situation of a great number of preparations present on modern pharmaceutical market.
Interaction of calcium and vitamin D3 can be called a classical example of such synergism. Vitamin D is considered to be a prohormone, which produces several active metabolites having hormone properties. Inside the liver vitamin D3 transforms into 25-(OH)D3, which is basically contained in blood. This form reabsorbes in intestinal canal during the process of entero-hepatic circulation. In kidneys and some other organs 25-(OH)D3 endures further hydroxylation with the formation of a more active metabolite – 1.25-(OH)2D3 (1.25 is a dihydroxycholecalciferol or calcitriol). Part of 1.25-(OH)2D3 is converted into one more form of the vitamin 24.24(OH)2D3 in intestines under control of oestrogens, which already on the level of cortical bone tissue stimulates transforming growth factor of osteoblasts (B-TGF) and results in calcium and phosphates fixation back to the bone tissue. At the same time B-TGF activates oestrogen block of osteoclast activity.
Overconcentration of calcium and phosphates is a sign to start additional calcitonin regulation, which with the help of insulin can foster calcium and phosphates fixation by osteoblasts, together with oestrogens stimulates formation of 24.25-(OH)2D3, and blocks calcium and phosphates absorption. At the same time there comes a signal to stop the work of parathyrin both from the side of high level of calcium and phosphates in blood and along the shunting line of inverse regulative connection from the side of 24.25-(OH)2D3. On the contrary, reduction of calcium and phosphates concentration is a signal for stopping calcitonin and starting parathyrin, which induces massive formation of 1.25-(OH)2D3 and blocks 24.25-(OH)2D3 at the same time [16].
Vitamin D deficiency arising from its insufficient consumption with food or the lack of sunlight in case of liver pathology causes development of hypocalcemia. In this case the physiological responce of the organism – the increase of parathyroif hormone secretion – does not lead to the desired effect as at insufficient calcitriol content mobilization of calcium from bone tissue under effect of parathyroid hormone does not start. Calcium absorption disorder in intestinal canal predisposes to the development of D hypovitaminosis, which, in its turn, may cause hypocalcemia or complicate the existing one [4, 6, 9].
Hypercalcemia is sometimes observed among patients who have endured kidney transplantation as far as some time after the operation is needed to restore metabolic function.
On the other hand, D hypervitaminosis may lead to hypercalcemia for the second time. It’s a well-proved fact that life guards from water stations are 110 times more subject to nephrolith as compared to people who live in the same place, but have a different profession. It was found to be connected with the life guards spending a lot of time exposed to sunlight. As a result of continous exposure to sunlight their skin forms vitamin D intensively, which leads to repeated hypercalcemia.
Collective intake of vitamins B12 and folic acid with ions of iron is widely used in modern medicine. It has been proved that the interactions that take part in this combination result in the improvement of hematosis processes [15, 18, 19].
Vitamin C has a protective effect over vitamin E and β-carotene, protecting it from being destroyed by free radicals. Vitamin C is a protector of folic acid reductase and takes part in distribution and accumulation of iron. Antioxidative effect of vitamin E is potentiated when combined with ascorbic acid, retinol, flavonoids. Vitamin E metabolism is closely connected with selenium. The effect of these antioxidants is synergic [7].
Vitamin B1 has vitamin-C-saving function and creates better conditions for using vitamin C by enzyme systems of the organism [7]. Riboflavin is needed to transform tryptophan into nicotinic acid and pyridoxine. Biotin is a synergist of vitamins B2, B6, A and nicotinic acid [14, 17, 20, 21].
Today we have brand-new vitamin and mineral complexes where the daily dose of vitamins and elements used is divided into several tablets, each of them having the structure completed on the basis of ionformation of positive and negative interaction between the components during the process of their production, storage and assimilation by the organism.
Division of the complex into several intakes allows to take into maximum consideration chronopharmacological aspects of bioavailability of vitamin and mineral products. For instance, it is generally known that iodine is better absorbed in the morning. Taking vitamin D in the evening is more preferrable. Maximum admission of calcium and phosphorus is marked to happen in the second half of the day as well.
Appearing of such vitamin and mineral complexes as “Alfavit” and “Vitamineral” where the daily dose of necessary micro- and macroelements is divided into different tablets with the consideration of their interactions with one another and with vitamins on the pharmaceutical market allows to solve the problem of “separately or together” in a way of reasonable compromise.
The right choice of preparation, its dosage, food influence on the components availability, length of treatment, chronopharmacological aspects, possibility of using it together with other medicines is a subject of serious reflection of a specialist prior to the beginning of vitamin therapy, which performs not only as a powerful instrument in providing vital activity to a sick person, but also in improving life quality of a healthy person.

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