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Back in 1975, the creator of Mildronate (also known as Meldonium), professor Kalvins, was studying all body chemicals that can be deplenished during endurance trainings. He found that one particular chemical - Gamma Butyrobetaine - is being deplenished under physical workloads. He changed this molecule by replacing one atom of Silicon with that of Nitrogen so that the new molecule would not decompose and could act as a transmitter from CNS to peripheral cells.
Mildronate was approved for use to general public in 1984. It is a metabolic enhancer that can normalise cellular energy metabolism. As such, it is usually used to treat angina, myocardial failure and reduce alcohol withdrawal symptoms. Off - label use of Meldonuim in otherwise healthy individuals includes increasing exercise tolerance, learning, memory and even sexual function.
Mildronate gained popularity after Sharapova, a famous tennis player, said that she has been taking this drug for the last 10 years because of healthy reasons. Also, a number of other world and olympic champions admitted taking it., e.g. world record holder in short track - Semen Elistratov, olympic champion figure skater - Ekaterina Bobrova, racing cyclist from team Katyusha - Eduard Varganov, world champion weightlifter Aleksey Lovchev and world champion runner from Sweden - Abeba Aregawi
Interesting facts about Mildronate:
- Latvia is selling about 70 million Euro of Mildronate annually, which is about 0.7% of the total exports of this country.
- The creator of the drug, professor Ivars Kalvins, claims that Meldonium has never been found to have anabolic properties; it is rather a cardioprotector that can protect cardiovascular system of athletes from ischemia under high physical workloads. He also says, that, as such, most athletes actually should use it to diminish the negative effects associated with high-intensity trainings.
- In 2015, 17% of Russian athletes were tested positive for Meldonium, compared with 2.2% athletes of other nationalities.
- Like Semax and Cerebrolysin, Mildronate is on the Russian List of Vital & Essential Drugs.
What Is Mildronate?
Mildronate is a popular solution for a wide range of health-improving effects. The drug improves metabolic processes within tissues, and can be used to treat various types of diseases in which there is an insufficient supply of nutrient supply to cells observed alongside with the accumulation of harmful decomposition products in them.
Mildronate, more precisely, its active substance meldonium, was synthesized in the late 70s in Latvia. Initially, Mildronat was used only as a veterinary agent, allowing accelerating the growth of farm animals. However, after the discovery of its cardioprotective agents, Mildronate became widely used in medicine. Currently, Mildronate is used to treat various cardiovascular diseases, to correct conditions of excessive physical and mental exhaustion. Athletes are prescribed a drug to restore physical strength.
Active Substance & Action Mechanism
According to the scientific literature, Mildronate emerged in Latvia in the 1970s in trials to increase the growth rate of meat animals. On February 15, 2016, PubMed has a total of 215 articles above keywords. The first was published in 1986 by Latvian researchers and concerned the metabolism in the heart, where it was shown that Mildronate improved energy metabolism in heart muscle cells. Additional 8 articles were published in Russian before the first came out – still with Russian authors – in English in 1988. Two Japanese articles in English were published in 1989, but before 1997 there were only two articles from Japan compared to 49 from Latvia, Russia and Ukraine.
From the year 2000, it can be established that the cardioprotective effect of the mesonium is well dispersed in Japan, from which a number of articles on experiments were published mainly in rats.
Dosage & Posology
Meldonium is taken with meals with sufficient amount of water. Dosages and posology are strictly individual and decided upon by the doctor. Here is a general scheme:
Cardiovascular disorders (in association with other drugs): 500-1000mg in one-two daily administrations for 4-6 weeks.
Chronic cerebrovascular disorders: 500mg once a day for 4-6 weeks.
Psycho-physical stress: 250mg four times a day for 10-14 days.
Withdrawal syndrome in chronic alcoholism (in combination with other drugs): 500mg four times a day for 7-10 days.
Given that the drug should be taken only in accordance with medical prescription, the dose must be adapted based on the need, in particular it should be reduced in elderly patients, as well as patients with moderate renal and / or hepatic insufficiency.
Mildronate is prescribed in countries where it is approved for angina pectoris and heart attacks. The concept behind it is the idea that the metabolism of the heart muscle in the case of ischemia, e.g. as a result of a coronary artery occlusion, should be switched from the aerobic to the anaerobic metabolism to supply the heart muscle cells despite lack of oxygen still with the necessary energy.
Mildronate Health Effects
Mildronate is an anti-ischemic drug developed for the treatment of cardiac ischemia, angina pectoris, ischemic cardiomyopathy and chronic heart failure. It has also found use in therapy in acute cerebrovascular insufficiency and in recovery after cerebral circulatory disorders and head trauma.
Mildronate acts by regulating energy metabolism, lowering the levels of L-carnitine, an amino acid, in order to prevent the accumulation of toxic intermediates.
Today it can be considered reasonably certain that the effect of meldonium can be traced to the mitochondria (the cell’s “power plant”), which is interesting because mitochondria are present in all cells in the body, which makes it possible that meldonium affects all organs in the body that could benefit from a better energy metabolism. This has been used to some extent in studies of neurons and thus there are small studies (or hypotheses) about using the preparation after stroke as well as at Parkinson’s and Alzheimer’s Diseases. However, one cannot see that there are scientific results that show that the preparation has some effect in these contexts.
There is a report claiming that Mildronate increases the alertness and another that the learning ability increases. Mildronate’s mechanism of action is linked to carnitine, which is a substance studied not least in sports contexts as dietary supplements. Carnitine is a transport molecule that is linked to the transport of long fatty acids across the inner mitochondrial membrane. One source of carnitine is meat, but carnitine can also be self-synthesized from the amino acids lysine and methionine.
Mildronate (both in short-term and long-term studies) reduces the carnitine content of the blood (in one four week study 18%) since mildronate inhibits the biosynthesis of carnitine and thus works as an inhibitor of the fatty acid oxidation. This affects the speed of the cell energy metabolism.
Mildronate has the following actions
In general, Mildronate has a positive effect on the body, manifested in improving performance, reducing over-voltage, both mental and physical. Also, the drug increases the level of humoral and cellular immunity.
Mildronate Side Effects
Generally meldonium is well tolerated and side effects are rare and mild. During the studies or in the post-marketing phase, cases of:
- allergic reactions (only in clinical studies)
- headache (in clinical studies only)
- indigestion (in clinical studies only)
- allergic dermatitis, urticaria
- agitation, anxiety, tremors
- sleep disorders
- dizziness, abnormal gait
- heart rate changes, heart rhythm disorders
There are no reported cases of overdose in the literature, however in case of accidental intake of an excessive amount of meldonium, it is necessary to check renal and hepatic function.
In people with pathological myocardial damage and heart failure, the drug is used to improve the metabolism of cardiac muscle cells. The cardioprotective effect of Mildronate in the treatment of coronary artery disease is the following:
- increased tolerance of the heart muscle to stress,
- reduction of necrosis,
- improvement of blood circulation in the affected area,
- reducing the duration of the rehabilitation period.
In patients suffering from chronic heart disease, the drug can reduce the incidence of angina attacks. Also, the drug, as indicated in the instructions, increases the strength of contractions of the heart muscle and the power of cardiac output. With regular intake, Mildronate slows down the rate of pathological processes occurring in the myocardium.
It should not be used:
- in case of hypersensitivity to the product
- severe renal and / or hepatic failure
- in patients under 18 years
- in pregnant or nursing women