In the complex treatment of various diseases with damage to nerves and spinal roots, B vitamins are often prescribed. And although vitamins are not drugs, their use improves the functional state of the nervous system and affects the course of the main pathological process.
One of the frequently used drugs is Neuromultivit, an original tablet product produced by the Austrian pharmaceutical company Lannacher Heilmittel.
Composition of Neuromultivit
Neuromultivit is a combined patented multivitamin complex. Main components of the drug:
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100 mg thiamine or vitamin B1;
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200 mg pyridoxine or vitamin B6;
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200 mg cyanocobalamin;
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excipients intended to stabilize the composition and give tablet required density (cellulose, povidone, magnesium stearate);
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substances that form a protective film shell.
All vitamins in composition Neuromultivita are water-soluble, they do not compete with each other and do not accumulate in the tissues of the human body. In addition, these substances are not synthesized by the body itself and come mainly from food. True, small amounts of thiamine and pyridoxine can be produced by intestinal microflora. But this is not enough to ensure normal functioning of the nervous system even in the absence of any diseases. It also happens that it is the deficiency of certain vitamins that causes or supports the appearance of neurological symptoms.
Thiamine after absorption in the upper intestines, it undergoes biotransformation and turns into cocarboxylase. This substance is an important coenzyme of many reactions and therefore participates in the regulation of the metabolism of proteins, fats and carbohydrates. It is also necessary for the conduction of nerve impulses and synaptic transmission of excitation to muscle fibers.
Pyridoxine is also absorbed in the small intestine and is quickly included in various metabolic processes in the body. With its participation, the synthesis of many enzymes, hormones, biologically active substances and neurotransmitters (compounds necessary for the finest processes of impulse transmission in the brain) occurs. Thus, with the help of vitamin B6, histamine, adrenaline, norepinephrine, serotonin, GABA, and dopamine are produced. This substance also improves muscle contractility, prevents the degeneration of pyramidal nerve cells and liver cells, and affects the content of cholesterol and lipids of different densities in the blood. Pyridoxine also promotes the activation of folic acid molecules, another vitamin necessary for normal hematopoiesis and the functioning of the nervous system.
Cyanocobalamin in the human body it is spent primarily on the process of formation of red blood cells, which provide oxygen to all tissues. In addition, its metabolites are involved in the processes of replication (reproduction) of nucleic acids, which affects cell reproduction and growth. In the nervous system, vitamin B12 is necessary for the regulation of lipid metabolism, the level of phospholipids and cerebrosides. Thanks to it, a normal myelin sheath is formed around the long processes of neurons, which ensures a high speed of nerve impulses.
Indications
Thanks to the vitamins B1, B6 and B12 included in the drug, Neuromultivit has neurotrophic and regenerative properties. It helps restore damaged and inflamed nerve fibers, improves metabolism in all tissues and especially in the central nervous system. The production of neurotransmitters is normalized, the work of nerve cells is harmonized. In addition, Neuromultivit is capable of exerting a moderate analgesic effect in cases of damage to the peripheral nervous system.
For what diseases and what helps Neuromultivitis? Indications for its use are:
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plexites of various origins;
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obturator canal syndrome, in which the sciatic nerve is pinched by a spasmodic muscle at the level of the pelvic outlet;
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polyneuritis (polyneuropathy) of diabetic, toxic, alcoholic and other etiology;
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neuritis of peripheral nerves;
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neuropathy of the facial nerve, which also includes Bell's palsy and prosoplegia;
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trigeminal neuralgia (syndrome caused by pathology of the trigeminal nerve), also called Fothergill's disease;
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intercostal neuralgia.
In addition, Neuromultivit is often used by neurologists in the complex treatment of various brain diseases. Although they are not direct indications for prescribing this drug, the use of this vitamin complex can have a beneficial effect on the functioning of the central nervous system. According to doctors, Neuromultivit can also be useful in the recovery period after injuries, operations, stress, and with a diagnosed deficiency of B vitamins.
Features of application
Neuromultivitis is usually prescribed in a daily dose of 1–3 tablets; recommendations depend on the clinical picture of the underlying disease. The duration of treatment and frequency of administration are determined by the doctor.
Since the tablets are coated with a protective film coating, Neuromultivit should be taken as a whole. Chewing or breaking may affect the pharmacokinetics of the drug. To reduce the irritant effect on the gastric mucosa, tablets are taken after meals.
Contraindications and side effects
Side effects when using Neuromultivit develop infrequently. This may include a rash and itching of an allergic nature, nausea, and tachycardia. If such reactions occur, you should inform your doctor about this; the drug will most likely be discontinued. In addition, the appearance of such side effects may indicate an overdose of certain vitamins.
Contraindications for prescribing Neuromultivit are intolerance to at least one component, children under 12 years of age. Research on the effectiveness and safety of the drug for children were not carried out. In addition, the presence of a film coating eliminates the possibility of dividing the tablet and selecting the dosage of Neuromultivit in accordance with the age of the child. During pregnancy and lactation, the drug is not prescribed due to the lack of proven safety of the drug for the body of a woman and child.
Precautionary measures
To avoid overdose, you should not take the drug for more than 4 weeks in a row, unless your doctor recommends a different treatment regimen. It is also undesirable to use other vitamin complexes at the same time. While taking Neuromultivit, you should avoid drinking alcohol, which is associated with poor compatibility of ethanol with vitamins and a decrease in the absorption of thiamine. Strong black tea works in a similar way.
It is important to remember the mutual influence of drugs. For example, simultaneous use of Neuromultivit and levodopa drugs can lead to a decrease in the effectiveness of antiparkinsonian therapy. Loop diuretics increase the excretion of thiamine (vitamin B1) from the body, and antacids impair its absorption in the gastrointestinal tract. The cytostatic 5-fluorouracil competes with thiamine and suppresses its transformation into cocarboxylase. Isoniazid, Cycloserine, Penicillamine, Hydrolasine and oral contraceptives increase the body's need for pyridoxine (vitamin B6).
What can be replaced
Autolysate of purified brewer's yeast.
In some cases the ability to choose a liquid form of release is an advantage of the drug over Neuromultivit.
When deciding to replace the original Neuromultivit with another drug, differences in the composition of vitamin complexes should be taken into account. They may contain other vitamins (in addition to B1, B6 and B12), and the concentration of the main components may be different from Neuromultivit. Only generics are its structural analogues, but these drugs do not undergo clinical trials.
It is impossible to answer unequivocally the question of what is better - Neuromultivit, Milgamma, Pentovit or other vitamin complexes of similar composition. A certain concentration of individual components, release form, and even the pharmaceutical company producing it - all this can serve as selection criteria. Therefore, you should listen to the recommendations of your doctor and consult him when replacing Neuromultivit with other drugs.
№ 9.4 Patients with hereditary ornithine cycle disorders avoid protein foods and experience vomiting, drowsiness, seizures, and mental retardation. Make suggestions about the causes of the observed phenomena. For this:
a) Write a diagram of the ornithine cycle, indicate the enzymes
b) Explain the biological role of the ornithine cycle
c) List the substances whose content is increased in the blood of such patients
d) Explain the toxic effect of one of these substances on nerve cells
Cause- hyperammonemia
A)Ornithine cycle
b) The ornithine cycle in the liver performs 2 functions:
1. The conversion of amino acid nitrogen into urea, which is excreted by us, prevents the accumulation of toxic products, mainly ammonia
2. Synthesis of arginine and replenishment of its fund in the body
V) The concentration of ammonia, carbamoyl phosphate, citrulline, and argininosuccinate may increase.
G)Mechanism of toxic action of ammonia on the brain and the body as a whole are obviously associated with its effect on several functional systems.
Ammonia easily penetrates through membranes into cells and in mitochondria shifts the reaction catalyzed by glutamate dehydrogenase towards the formation of glutamate:
a-Ketoglutarate + NADH + H + + NH 3 → Glutamate + NAD + .
A decrease in the concentration of a-ketoglutarate causes:
oppression exchange of amino acids (transamination reaction) and, consequently, the synthesis of neurotransmitters from them (acetylcholine, dopamine, etc.); hypoenergetic state as a result of a decrease in the speed of the flow cycle.
Insufficiency of α-ketoglutarate leads to a decrease in the concentration of metabolites of the TCA cycle, which causes an acceleration of the reaction of oxaloacetate synthesis from pyruvate, accompanied by intensive consumption of CO 2. Increased production and consumption of carbon dioxide during hyperammonemia is especially characteristic of brain cells.
An increase in the concentration of ammonia in the blood shifts the pH to the alkaline side (causes alkalosis). This, in turn, increases the affinity of hemoglobin for oxygen, which leads to tissue hypoxia, accumulation of CO 2 and a hypoenergetic state, which mainly affects the brain.
High concentrations of ammonia stimulate glutamine synthesis from glutamate in nervous tissue (with the participation of glutamine synthetase):
Glutamate + NH 3 + ATP → Glutamine + ADP + H 3 PO 4.
The accumulation of glutamine in neuroglial cells leads to an increase in osmotic pressure in them, swelling of astrocytes, and in high concentrations can cause brain edema. Reduced glutamate concentration disrupts the metabolism of amino acids and neurotransmitters, in particular synthesisγ-aminobutyric acids (GABA), main inhibitory neurotransmitter. With a lack of GABA and other mediators, the conduction of nerve impulses is disrupted and convulsions occur.
The NH 4 + ion practically does not penetrate into cytoplasmic and mitochondrial membranes. An excess of ammonium ion in the blood can disrupt the transmembrane transport of monovalent cations Na + and K +, competing with them for ion channels, which also affects the conduction of nerve impulses.
An original development by Merck, used in 75 countries around the world
B vitamins in the treatment of diseases of the nervous system
B-group Vitamins In The Treatment Of Nervous System Diseases
Ya.A. Starchina I.M. Sechenov Moscow Medical Academy
- The paper considers the role of B-group vitamins in nervous system performance and the possibilities of their use in the treatment of nervoussystem diseases as solo drugs in mono- and polyneuropathies of varying genesis and in pain syndromes. The prospects for using the vitamin complex Neurobin are discussed.
Key words: thiamine, pyridoxine, cyancobalamine, polyneuropathy, pain syndrome, Neurobin. Yulia Alexandrovna Starchina:
[email protected]
B vitamins, primarily B1 (thiamine), B6 (pyridoxine), B12 (cyanocobalamin), are neurotropic and have been used for many years in the treatment of diseases of the peripheral nervous system and central nervous system. All three vitamins of this group play a special role in intermediate metabolism occurring in the central nervous system and peripheral nervous system.
The daily requirement for vitamin B1 is 1.3-2.6 mg. It increases in older people and in women during pregnancy and breastfeeding, as well as with hyperthyroidism, heavy metal poisoning, smoking, stress and alcohol abuse. Thiamine, localized in the membranes of nerve cells, is involved in the processes of regeneration of damaged nerve fibers, energy processes in nerve cells, the formation of the structure of neuronal membranes and the normal function of axonal transport.
Vitamin B6 is no less important, especially for bottle-fed children, pregnant women and people taking antibiotics for a long time. The daily requirement of vitamin B6 for an adult is 1.5-3 mg, for children under 1 year of age - 0.3-0.6 mg, for lactating and pregnant women - 2-2.2 mg. Vitamin B6 is actively involved in amino acid metabolism, protein and fat metabolism, and immune reactions.
Vitamin B12 plays an important role in cell division, regulation of fat and amino acid metabolism, and hematopoiesis. The daily requirement of vitamin B12 for adults is from 2 to 3 mcg/day, for children - from 0.3 to 1 mcg/day, for pregnant and lactating women - from 2.6 to 4 mcg/day. It is involved in the most important biochemical processes of myelination of nerve fibers.
B vitamins are prescribed for nutritional deficiency, alcohol abuse, and malabsorption syndrome. B complexes of vitamins are often used to stimulate natural mechanisms for restoring the function of nerve tissue in polyneuropathies of various origins, and for the treatment of pain syndromes.
Deficiency of any of the B vitamins leads to the formation of polyneuropathy. With chronic thiamine deficiency, the development of distal sensory-motor polyneuropathy, reminiscent of alcoholic and diabetic ones, is possible. With a lack of pyridoxine, distal symmetrical, predominantly sensory, polyneuropathy occurs, manifested by a feeling of numbness and paresthesia. Lack of cobalamin is associated primarily with pernicious anemia, subacute degeneration of the spinal cord with damage to the posterior cords, while in some cases distal sensory peripheral polyneuropathy is formed, characterized by numbness and loss of tendon reflexes.
Thiamine deficiency and the toxic effect of ethanol play a large role in the development of alcoholic polyneuropathy, which in Russia is one of the most common forms of generalized damage to peripheral nerves and occurs in 10% of people aged 40-70 years suffering from alcoholism. In alcoholism, there is a deficiency of thiamine. It can also be caused by an unbalanced, mainly carbohydrate, diet. In addition, large amounts of vitamin B1 are required to utilize alcohol. The absorption of thiamine and other B vitamins is impaired due to the development of malabsorption syndrome. These disorders lead to metabolic changes with myelin destruction and axonal degeneration. In most cases, alcoholic polyneuropathy develops slowly, initially the distal parts of the lower extremities are involved in the process, then their proximal parts and distal parts of the upper extremities, and axonal damage to the peripheral nerves is detected. In a large study
T.J. Peters et al. 325 patients with a sensory form of alcoholic polyneuropathy received an oral B vitamin complex for 12 weeks. Patients of the 1st group were prescribed only a complex of vitamins of group B, the 2nd group - additional folic acid (1 mg), the 3rd group - a placebo. In patients of the first two groups, compared with placebo, there was a significant decrease in the intensity of pain, improvement in vibration sensitivity and performance of coordination tests. It is important to note that the addition of folic acid did not affect the dynamics of symptoms. The results obtained confirm the advisability of prescribing a B complex of vitamins to patients with alcoholic polyneuropathy, regardless of its origin (ethanol or thiamine). Considering that deficiency of B vitamins plays a leading role in the development of other forms of damage to the nervous system in alcoholism (Haye-Wernicke-Korsakoff encephalopathy, alcoholic dementia), it is advisable to prescribe them in these cases.
Complex preparations of B vitamins are widely used in the treatment of diabetic polyneuropathy. The positive effect of thiamine on the biochemical processes of glucose metabolism is known due to the activation of the transketolase enzyme. The administration of thiamine reduces lipid peroxidation, the severity of oxidative stress, endothelial dysfunction, and the content of non-enzymatic glycation products in diabetic polyneuropathy. The experiment demonstrated its ability to reduce hypoperfusion and improve tissue oxygenation, restore endothelium-dependent vasodilation and inhibit apoptosis. It is believed that vitamins B6 and B12 also play a positive role. Thus, the use of vitamin B12 in diabetic polyneuropathy reduces pain, paresthesia and the severity of damage to the autonomic nervous system, as evidenced by the analysis of 7 clinical controlled studies conducted in 1954-2004. .
Combined preparations of B vitamins are also used for complex therapy of acute pain syndromes. In the middle of the last century, the analgesic effect of such therapy was established. Clinical experience shows that intramuscular administration of a combination of thiamine, pyridoxine and cyanocobalamin helps relieve pain, normalizes reflex reactions, and reduces sensitivity disorders. Therefore, for various pain syndromes, they often resort to using vitamins of this group in combination with other drugs. Numerous studies have proven that under the influence of B vitamins, patients with acute back pain experience clinical improvement; suggest that vitamin B12 has the most pronounced analgesic properties. Experimental and clinical research on B vitamins continues. Thus, during the experiments it was revealed that under the influence of a combination of B vitamins, nociceptive responses caused by formaldehyde are inhibited, which is not observed after the administration of naloxone. It is believed that the antinociceptive effect of the combined vitamin complex may be due to inhibition of synthesis and/or blocking the action of inflammatory mediators. It has also been established that the B complex of vitamins enhances the effect of the main antinociceptive neurotransmitters - norepinephrine and serotonin. In addition, an experiment on rats revealed suppression of nociceptive responses not only in the dorsal horn of the spinal cord, but also in the thalamus optica. Clinically and in experimental models, it has been shown that co-administration with B vitamins enhances the analgesic effect of non-steroidal anti-inflammatory drugs, the anti-allodynic effect of gabapentin, dexamethasone and valproate in neuropathies. As a result, treatment time and the risk of side effects are reduced.
The antinociceptive effect of B vitamins is of particular interest in the treatment of tunnel syndromes, in particular the so common carpal tunnel syndrome. In a study of 994 patients with carpal tunnel syndrome, it was shown that with combination therapy, including vitamin B6, improvement occurred in 68% of patients, and with similar treatment, but without pyridoxine, only in 14.3%. According to a review of 14 studies on the effectiveness of pyridoxine in this syndrome, 8 studies confirmed a decrease in clinical manifestations and the severity of electrophysiological disturbances in carpal syndrome in patients receiving vitamin B6, which may be associated with its antinociceptive effect or with replenishment of the deficiency of this vitamin, with which may cause paresthesia and numbness of the hands.
The use of the complex multivitamin preparation Neurobion, containing a combination of B vitamins: thiamine (B1), pyridoxine (B6) and cyanocobalamin (B12), in combination therapy for a number of diseases of the nervous system seems very promising. One Neurobion tablet contains thiamine disulfide - 100 mg, pyridoxine hydrochloride - 200 mg and cyanocobalamin - 240 mcg. It should be noted that one ampoule of Neurobion also contains three vitamins: thiamine - 100 mg, pyridoxine (100 mg) and cyanocobalamin (1 mg), which provides maximum neuroprotective effect). An important advantage of Neurobion is the availability of oral (tablets) and parenteral (injection solution) dosage forms, which allows for maximum individualization of treatment, effectively combining relatively short-term parenteral courses of treatment and long-term oral maintenance administration of the drug, and also significantly increases adherence to therapy. Another advantage of the drug is the optimally balanced ratio of doses of its constituent vitamins.
In a multicenter study conducted by German scientists in 418 patients with the acute phase of painful radicular syndrome, the effectiveness of diclofenac 25 mg and a combination of diclofenac 25 mg with vitamins B1 50 mg, B6 50 mg and B12 0.25 mg were compared for 2 weeks of treatment. When a clinical effect was achieved, treatment was stopped after 1 week. In patients receiving combination therapy, a statistically significant faster development of the therapeutic effect and greater effectiveness of treatment, assessed by the characteristics of the pain syndrome, were noted, with the best effect obtained in patients with a greater severity of the radicular syndrome.
Another study, also conducted by German scientists, assessed the effect of long-term therapy with Neurobion on the incidence of relapse-free acute radicular syndrome in the cervical or lumbosacral region. 30 patients with the acute phase of radicular syndrome received combination therapy with Neurofenac (a combination of diclofenac with B vitamins) for 3 weeks, and with Neurobion for the next 6 months. Another 29 patients with the acute phase of radicular syndrome were prescribed diclofenac only, followed by placebo for 6 months. A statistically significant decrease in the number of relapses of radicular syndrome was found in the group receiving Neurobion therapy (32% versus 60% in the placebo group); in the event of a relapse, its severity was the same in both groups. The number of patients without pain within 6 months in the group receiving Neurobion was significantly higher (43% versus 16%). When pain syndrome occurred, 29% of patients treated with Neurobion complained of “severe” pain in intensity, compared to 56% of patients in the placebo group.
The administration of B vitamins for various diseases of the nervous system allows, on the one hand, to compensate for the existing deficiency (possibly due to the body’s increased need for B vitamins due to the disease), and on the other hand, to stimulate natural mechanisms for restoring the function of nerve tissues. The analgesic effect of the B vitamin complex has also been proven.
In the near future, Neurobion, widely known abroad, will appear on the domestic market. Undoubtedly, the drug will take its rightful place in the complex treatment of mononeuropathies, pain syndromes caused by degenerative changes in the spine, neuropathy of the facial nerve, trigeminal neuralgia, and polyneuropathies of various etiologies.
LITERATURE HURRAY
Cramps are a fairly common occurrence and involve involuntary contraction or tension of one muscle or muscle groups. The causes of cramps are varied: muscle fatigue, prolonged strength training, swimming in cold water, dehydration, physical inactivity, neuroses, diseases (polyneuritis, hypoparathyroidism, diabetes, varicose veins, thrombophlebitis, etc.). The frequency of seizures increases during stressful situations, overwork, and hypothermia. In old age, seizures are associated with degenerative processes in muscle and nervous tissue.
In the complex treatment of diseases accompanied by muscle cramps, vitamin therapy and minerals are important.
Vitamins that prevent seizures
B vitamins, due to their participation in numerous enzymatic reactions of the body, have a therapeutic effect for seizures of various etiologies.
- Vitamin B1 (thiamine) is one of the main vitamins responsible for the transmission of nerve impulses. Thiamine is involved in the activation of enzymes that supply oxygen to tissues, including muscle tissue. Oxygen starvation of a muscle leads to its convulsive contraction.
- Vitamin B2 (riboflavin) prevents the risk of muscle spasms by participating in the transmission of electrical charge in the cell. Riboflavin is necessary for the normal functioning of the sodium-potassium pump, which plays an important role in the conduction of nerve impulses.
- Vitamin B6 (pyridoxine) is one of the main vitamins that prevents the development of pyridoxine-dependent seizures in newborns. In adults, vitamin B6 is involved in the conduction of nerve impulses and hematopoiesis. These properties of pyridoxine determine its therapeutic effect in convulsive syndrome.
- Vitamin B12 (cyanocobalamin) deficiency causes muscle cramps, especially at night. The participation of the vitamin in the pathogenesis of this phenomenon is to regulate the blood supply to tissues and enrich them with oxygen. The vitamin regulates biochemical processes and participates in enzymatic processes during the transmission of nerve impulses.
Vitamin D plays an important role in the pathogenesis of diseases such as hypoparathyroidism, accompanied by muscle spasms. With hypoparathyroidism, the production of parathyroid hormone by the thyroid gland decreases. This hormone is responsible for the metabolism of calcium in the body. The balance between calcium and magnesium ions is disrupted, which is accompanied by an increase in neuromuscular excitability (convulsions). The vitamin is necessary for the absorption of calcium and magnesium, since it is their deficiency that causes muscle cramps.
Vitamin E has a vasodilating effect and reduces blood viscosity. These properties of the vitamin are important if the cause of seizures is a violation of the blood supply to the extremities. Taking vitamin E helps normalize blood flow and reduces nighttime cramps in the calf muscles.
Trace elements and minerals
Of the mineral substances that prevent the development of seizures and reduce seizure syndrome, the most important are magnesium, calcium, potassium, and sodium.
Magnesium is one of the main anticonvulsant microelements. The mechanism of its action is that it prevents the penetration of calcium into the cell. It is the high calcium content inside the cell that causes it to go into spasm. Magnesium blocks this process and prevents convulsive muscle contraction. The cellular potassium-sodium pump also requires magnesium to function. Thanks to this mechanism, the cell contracts and relaxes.
Calcium has been successfully used in the treatment of seizures of various origins. The element is responsible for neuromuscular excitability and maintaining acid-base balance. Hypocalcemia can be accompanied not only by isolated spasms of muscle groups, but also by tetany. Calcium deficiency occurs with hypoparathyroidism and is aggravated by vitamin D deficiency.
Potassium and sodium are the main components of the complex sodium-potassium pump mechanism. Its function is to regulate the processes of nerve impulse transmission and maintain osmotic pressure in the cell. With a deficiency of these minerals, weakness and muscle cramps occur.
Vitamin preparations to combat seizures
In the complex therapy of convulsive syndrome, the following vitamin and mineral preparations are used:
- Complivit Magnesium. The drug contains B vitamins, calcium and magnesium.
- Combilipen. Neurotropic drug containing vitamins B1, B6 and B12.
- Magnesium preparations: Magnerot, Magnesium plus, Magne B6.
- Calcium preparations: Calcemin Advance, Calcium D3-nycomed.
The listed vitamin complexes do not have strictly anticonvulsant properties. Only a doctor can prescribe vitamins and minerals for cramps, having determined the true cause of muscle spasms.
Traditionally, B vitamins are used in practical medicine for the correction of various diseases of the central and peripheral nervous system, including mono- and polyneuropathies, encephalo- and myelopathy of deficiency origin, as well as for systemic diseases associated with a proven deficiency of vitamins of this group. Numerous clinical studies have proven their role in many biochemical reactions in neuronal cells. Therefore, the earliest symptoms in deficiency conditions appear precisely from the nervous system. Mental changes appear, manifested in increased irritability, fearfulness, and a tendency to hallucinate. More serious disorders of higher nervous activity are manifested in loss of the ability to concentrate, loss of memory for recent events, and impaired thinking abilities. Subsequently, as the deficiency worsens, disturbances in the activity of the peripheral nervous system occur: sensitivity disorders, paresthesia, severe pain along the nerves in the lower extremities, up to muscle weakness, paralysis and muscle atrophy occur.
Physiological role of B vitamins
Thiamine (vitamin B1) is a coenzyme in the oxidative decarboxylation reactions of alpha-ketoglutaric and pyruvic acids, participates in the processes of protein synthesis and mechanisms of regeneration of damaged nervous tissue, regulates protein and carbohydrate metabolism in the cell, affects the conduction of nerve impulses, and promotes the development of an analgesic effect. These properties of thiamine ensure its ability to slow down the progression of vascular damage in various pathological processes. Thiamine improves glucose metabolism with the initiation of the pentose phosphate pathway, resulting in increased energy production in nerve cells to ensure axoplasmic transport. The introduction of thiamine into the body allows to reduce the concentration of advanced glycation end products in tissues in case of carbohydrate metabolism disorders, prevents the development of endothelial dysfunction and damage to the vascular wall.
Pyridoxine (vitamin B6) is a cofactor for many enzymes acting in the cells of nervous tissue, participates in the reactions of decarboxylation and transamination of amino acids in various tissues, in the synthesis of neurotransmitters, and supports the synthesis of transport proteins in nerves. Good results have been obtained from its use in patients with various lesions of the peripheral nervous system: polyneuropathies of various origins, spondylogenic dorsopathies, discogenic radiculopathies.
Cyanocobalamin (vitamin B12) plays an important role in the processes of energy supply to cells. The main function of the active coenzyme forms of cobalamin (methylcobalamin and deoxyadenosylcobalamin) is the transfer of methyl groups (transmethylation) and hydrogen ions, due to which it plays an important role in amino acid and protein metabolism. Cobalamin is also involved in the synthesis of choline, methionine, creatinine and deoxyribonucleotides. Vitamin B12 is necessary for hematopoiesis (antianemic, erythropoietic, hematopoietic action), activation of the blood coagulation system, formation of epithelial cells, ensuring the normal functioning of the nervous system (participates in the formation of myelin), ensuring regeneration and tissue growth.
Vitamin B12 deficiency is manifested primarily by pernicious anemia and various neurological disorders. Such disorders in B12 deficiency, including dementia, other mental disorders, funicular myelosis and polyneuropathy, may occur without characteristic hematological changes in approximately 15% of patients.
Clinical applications of B vitamins
In neurological practice, among the B vitamins, the combination of vitamins B1, B6 and B12 can currently be considered the most popular and physiologically justified. These vitamins can act as synergists, and their combined use results in a more noticeable therapeutic effect. Experimental studies have shown that combinations of vitamins can inhibit the conduction of pain impulses at the level of the dorsal horns of the spinal cord and thalamus.
Vitamins B1, B6, B12 in some cases are useful even in the absence of their deficiency due to their active participation in biochemical processes that ensure the normal functioning of the structures of the nervous system, for example, in diabetic polyneuropathy and the treatment of pain syndromes. Therefore, B vitamins are often called neurotropic. In addition, thiamine, pyridoxine, and cyanocobalamin in high doses have been found to exhibit novel medicinal properties that differ from the well-known physiological effects of natural amounts of the vitamins.
Pyridoxine is known to have a positive effect on various types of epilepsy, and its use is recommended for treatment-resistant forms with very early onset (Wang, 2007). Therapeutic doses of pyridoxine from 50 mg/day in some cases can completely stop attacks. In some cases, pyridoxine reduces or stops the side effects of anticonvulsants, and also exhibits an antidepressant effect associated with its participation as a cofactor in the synthesis of catecholamines.
Thiamine has a positive effect not only in polyneuropathies associated with its deficiency, but also in toxic alcoholic polyneuropathy, Wernicke encephalopathy and alcoholic dementia. In numerous trials examining alcoholic patients with polyneuropathy who did not have thiamine deficiency, it was revealed that in this case, predominantly damage to small fibers develops, which differs in clinical, neurophysiological and pathomorphological characteristics from thiamine deficiency polyneuropathy.
Clinicians have long known the ability of thiamine, pyridoxine and cobalamin to reduce pain intensity. Many works by modern authors emphasize that both combination and separate use of vitamins B1, B6 and B12 have an analgesic effect. Vitamins have a possible analgesic effect directly on pain receptors and sodium channels of damaged membranes of sensory fibers. The clear analgesic effect of vitamins and their complexes has been confirmed by numerous experimental studies in neuropathic pain. In 2000, the first randomized placebo-controlled trial of intramuscular vitamin B12 injections for chronic back pain was conducted, the results of which showed a significant reduction in pain and improvement in motor function (Mauro et al., 2000).
There are also studies that compared the effectiveness of vitamin B12 with the antidepressant nortriptyline in the treatment of neuropathic pain in patients with diabetic polyneuropathy. There was a significant reduction in pain in the group receiving vitamin B12 injections compared to the group receiving nortriptyline. There was a significant decrease in paresthesia, burning sensation and chilliness (Talaei et al., 2009).
Studying the effectiveness of thiamine in diabetic and/or alcoholic polyneuropathy, scientists came to the conclusion that large doses of this vitamin can provide a short-term decrease in the intensity of pain, paresthesia, and improvement in temperature and vibration sensitivity (Mamchur V.I.).
Vitamin B6 is most often used in the treatment of pain associated with carpal tunnel syndromes. However, it should be noted that pyridoxine in large doses can cause a toxic effect. Currently, a dose of 200 mg/day is considered safe for the treatment of carpal tunnel syndrome. At a higher daily dose, it is recommended to monitor its concentration in the blood due to the risk of toxic effects (sensory neuropathy) at a daily dose above 500 mg. In the treatment of carpal tunnel syndrome, it is recommended to combine vitamin B6 with nonsteroidal anti-inflammatory drugs (NSAIDs) for 3 months. Many studies emphasize that in the treatment of pain, a combination of vitamins B1, B6 and B12 is more effective than monotherapy with any of these vitamins.
In recent years, the possibility of using B vitamins for vascular and neurodegenerative diseases has been actively studied. Complex therapy with vitamins B1, B6 and B12 reduces homocysteine levels in humans, the increase of which is a risk factor for the development of atherosclerosis, thrombosis, cerebrovascular diseases and dementia, increases endothelial dysfunction and oxidative stress. Clinical experience shows that parenteral use of thiamine (B1), pyridoxine (B6) and cyanocobalamin (B12) in combination is well combined with other drugs, and such therapy is usually well tolerated. Most often they are prescribed together with NSAIDs, since vitamins potentiate and prolong the effects of the latter, which makes it possible to reduce the dose of NSAIDs and achieve complete elimination of pain in the lower back in a shorter period of treatment.
Features of the drug Milgamma® and its prescription regimen
Milgamma® ampoules contain vitamins B1, B6 and B12 in therapeutic doses in combination with lidocaine. A 2 ml ampoule for one administration contains 100 mg of thiamine hydrochloride, 100 mg of pyridoxine hydrochloride, 1 mg of cyanocobalamin and 20 mg of lidocaine hydrochloride. The small volume of the drug for a single injection, as well as the local anesthetic lidocaine, which is part of the drug, makes Milgamma® injections practically painless and increases patient adherence to therapy.
Thanks to innovative technologies, one Milgamma® ampoule combines several active ingredients that were previously traditionally administered separately. Therefore, in addition to effectiveness and high quality, this multivitamin complex has another positive property - ease of use: instead of three intramuscular injections, one is enough. The use of high doses of B vitamins in the Milgamma® ampoule helps achieve maximum neuroprotective effect.
According to a double-blind, placebo-controlled study conducted by Stracke et al., parenteral administration of vitamins B1, B6, B12 in patients with diabetic neuropathy leads to an increase in peroneal nerve conduction velocity and improvement in vibration sensitivity. Moreover, these effects persist for at least 9 months.
According to the results of a study conducted by Winkler et al., the use of higher dosages of vitamins B1, B6 (daily dose of benfotiamine is more than 300 mg/day) more effectively reduces pain, improves vibration sensitivity and increases the speed of conduction along motor fibers than the use of more its low doses. According to A.L. Vertkin and V.V. Gorodetsky (2005), in patients with diabetic polyneuropathy during 6 weeks of taking Milgamma® tablets (1 tablet 3 times a day), there was an increase in the amplitude of the M-response and the speed of propagation of excitation along the motor fibers of the peroneal nerve, the amplitude of the action potential and the speed of propagation stimulation along the sensory fibers of the sural nerve, as well as improving the performance of autonomic cardiovascular tests.
The drug also turned out to be effective in the treatment of facial pain (typical and atypical prosopalgia), as evidenced by the results of a study by S.A. Likhacheva et al. It was noted that after the course of treatment, the intensity of the pain syndrome significantly decreases, quality of life indicators improve, and normalization of vegetative-vascular disorders in the facial area is noted. At the same time, the drug is well tolerated, which ensures high compliance.
During its existence on the Ukrainian market, the complex drug Milgamma®, which has a good evidence base, has taken a strong place in clinical practice, demonstrating high therapeutic efficacy and excellent tolerability. The availability of the drug in injectable and tablet forms allows for so-called step therapy, ensuring continuity between the stages of inpatient and outpatient treatment.
conclusions
The use of balanced therapeutic and prophylactic complexes of B vitamins is an integral part of the treatment and rehabilitation of neurological patients, including in the absence of a deficiency of these vitamins (for example, in diabetic polyneuropathy, pain syndrome) (Strokov et al., 2009). The effectiveness of therapy when using such complexes certainly increases.
The complex drug Milgamma® contains a combination of B vitamins and takes a strong place in the treatment of various lesions of both the central and peripheral nervous systems. The drug has high therapeutic efficacy, and due to the combined action of vitamins B1, B6, B12 and potentiation of their effects, higher clinical effectiveness is achieved than when using these vitamins separately. The composition and features of pharmaceutical technology and production ensure the stability of the dosage form, a favorable pharmacokinetic profile, and high therapeutic efficacy of the drug.
Prepared Tatiana Antonyuk