Meldonium Overview: Clinical Uses, Doping Controversy, COVID-19 Research, and Safety

Off-label use of Meldonium includes increasing exercise tolerance in sports, learning, memory, and even sexual function. It goes in three forms:

Meldonium, under the brand name Mildronate, was approved for commercial use in 1984 to enhance performance during rehabilitation and in response to psychological and physical overload.
According to The Washington Post, Mildronate was used to help Soviet soldiers combat stress during the Afghan War. Some sources even claim that it was actually the initial purpose of Meldonium creation: the survival of the body in extreme situations, high physical and psycho-emotional stress, lack of oxygen, high or low temperatures, and so on.

Today, Mildronate (Meldonium) is produced by the Latvian company Grindeks. It is also available for purchase by the general public in some CIS countries without a prescription.  

Meldonium is the active molecule of Mildronate. It has a chemical structure similar to that of the amino acid, and it is known as 3-(2,2,2-Trimethylhydrazinium) propionate dihydrate. It has long been used to treat myocardial and cerebral ischemia.

Inhibition of the organic cation transporter/carnitine type 2 (OCTN2) by Meldonium is accompanied by a decrease in L-carnitine concentration. Reduced L-carnitine availability decreases acylcarnitine formation by carnitine-palmitoyltransferase-1 (CPT1). In addition, Meldonium reduces the formation of trimethylamine (TMA) from L-carnitine by the intestinal microbiota and promotes the excretion of trimethylamine-N-oxide (TMAO). This determines the cardioprotective, anti-atherosclerotic, and anti-diabetic effects of Meldonium.

Thus, Meldonium reduces the risk of mitochondrial damage mediated by long-chain fatty acid metabolism and shifts energy production from fatty acid oxidation to glycolysis, a process that requires less oxygen. This situation is more favorable in ischemic conditions. Meldonium reduces the concentration of methemoglobin and therefore promotes greater O₂ transport by erythrocytes.

In simpler terms:

Under ischemic conditions, Meldonium can restore the balance between oxygen delivery and consumption in cells, thereby preventing the disruption of adenosine triphosphate (ATP) transport. At the same time, it activates glycolysis, a process that proceeds without additional oxygen consumption. As a result of a decrease in the concentration of carnitine, gamma-butyrobetaine, which has vasodilatory properties, is synthesized intensively.

The mechanism of action determines the variety of Meldonium pharmacological benefits [8] [9] [10]:

Mildronate is a popular and affordable choice among athletes. What is the use of Meldonium for bodybuilding? Why do athletes use Meldonium medication? And how does it influence the recovery process after physical exertion?

As studies have shown, the drug Meldonium helps cells adapt more quickly to energy starvation and enhances metabolism. Thanks to Mildronate, metabolic processes in immune cells normalize, and this contributes to strengthening the body’s protective potential. 

Mildronate can protect cardiac muscle cells from oxygen deficiency. If there is a balance between the flow of oxygen to the tissues and the need for it in the cells, the body’s resistance to stress increases, exhaustion goes away, and there is an increase in blood flow, slowing the process of cell death. 

Under the action of the drug, the heart muscle is able to contract more vigorously and infrequently, thereby increasing the cardiac muscle's tolerance to stress. In addition, Mildronate leads to a reduction in brain damage, and coordination of movements improves. Mildronate also has a favorable effect on the blood vessels. Another substance used by athletes and professional sportsmen for similar metabolic and recovery benefits is Actovegin. You can read more about it in our dedicated article.

Mildronate gained popularity worldwide after Maria Sharapova's meldonium scandal. The famous Russian tennis player confirmed that she has been taking Mildronate for several years. The investigation resulted in Sharapova's drug suspension. According to The New York Times post, after being accused of drug use, Sharapova essentially retired from big-time sports.

Still, Maria Sharapova was not the only one who had been taking the banned substance. A great number of other world and Olympic champions admitted to taking it. Read the Meldonium Wikipedia page for more information. 

In response to doping accusations, the creator of the drug, Professor Kalvins, claimed that Meldonium had never been found to have anabolic properties. Rather, it was designed as a cardioprotector that can protect the cardiovascular system of athletes under high physical workloads from ischemia. 

In one interview, Dr. Kalvins defined doping as a substance that can make a person perform above the norm, which makes it unsafe to use. Unlike doping compounds, according to Dr. Kalvins, Mildronate does not have this effect. It only helps athletes reach their maximum and minimize the undesirable consequences of intensive training processes on their health.

Nevertheless, Meldonium has been on the World Anti-Doping Agency (WADA) list of banned substances since 1 January 2016 because of the evidence of its use by athletes. And WADA officials refuse to cancel this decision. 

Interestingly, Trimetazidine, which is a Meldonium equivalent in the US, is also included in the list of substances banned by WADA. 

Today, new clinical data are emerging on the efficacy of Meldonium in treating coronavirus infections. We must also mention some of the studies in this Meldonium review.

The main focus is post-COVID syndrome, a complex condition characterized by vascular endothelial dysfunction, the development of coagulopathies with microthrombopathies, and subsequent organ and tissue damage.

One of the studies was conducted in 2020 by a group of researchers who aimed to evaluate the use of Mildronate as a metabolic corrector in patients with coronavirus pneumonia and chronic heart failure. The results showed a statistically significant reduction in hospitalization time in the Mildronate group compared to the control group. 

There was a significant decrease in C-reactive protein and D-dimer levels by the time of patients’ discharge. The drug was administered as follows: an IV injection of a solution (0.5 g/5 mL) of 1 g per day during the entire hospital stay, followed by outpatient oral capsules at a dose of 500 mg twice daily for up to 2 weeks. After 3 months, a significant improvement in quality of life and a decrease in the severity of asthenic syndrome were observed in the Mildronate group. 

In the work of E.Yu. Ebzeeva et al. (2020) [24], a positive effect of Mildronate was noted when prescribed as a corrector of the post-COVID asthenic syndrome. Meldonium was administered orally at 500 mg twice a day for 14 days.  

Mildronate also has immunomodulatory effects at the cellular and humoral immunity levels, including the production of circulating complexes, interferon, and an increased antiviral immune response. It has been shown to increase the total T-system values and the ratio of T-helper and T-suppressor populations. Additionally, it had an impact on the levels of IgM, IgA, and IgG. [2] [3] [7]

It was demonstrated that the drug can induce interferon in mice when administered simultaneously with the antigen. And it shows a protective effect against the influenza virus when used in accordance with therapeutic and preventive regimens.

When studying the immunoadjuvant action of Mildronate during vaccination with inactivated influenza vaccine in 1992, O.I. Kubar et al concluded that the use of Mildronate contributed to a statistically significant increase in the effectiveness of vaccine prevention and an increase in the multiplicity of growth of specific influenza antibodies. 

For more information, please refer to the official instructions.

According to the producer and some other medical specialists, Meldonium is low-toxic and does not cause severe adverse reactions compared to other drugs that are used by athletes. However, some side effects are still possible. They may include allergies, decreased blood pressure accompanied by headaches, tachycardia, dizziness, and general weakness, among others.

Another reaction to Meldonium that is sometimes reported by athletes is a sense of addiction. It means that if an athlete who has been taking it consistently for a long period of time misses a dose, they may feel less self-confident during the competition. Nevertheless, there is no official data supporting these anecdotal Meldonium experiences. So, it may well be a placebo.  

Mildronate (Meldonium) is an officially manufactured compound in Latvia. It is a non-prescription drug with a dose of 250mg in countries like Russia, Ukraine, and some others.

Meldonium is not licensed by the Food and Drug Administration (FDA) for use in the United States and is not authorized in the rest of Europe, which means that doctors in these countries cannot prescribe Mildronate. However, you can still buy it online for personal use.

There are many anecdotal reviews of Mildronate on Reddit. This one is devoted to discussing the effects of Mildronate as a mild stimulator and cognitive enhancer that may improve mood and reduce fatigue. It suggests that Meldonium may also have positive interactions with other nootropic compounds (presumably due to improved blood flow and absorption of the other compounds). Another thread is devoted to Meldonium for cardio. 

Have you used Meldonium and have something to say about its effects? Share your experiences on our Subreddit. 

Mildronate is manufactured by Grindeks. It is a Latvian company that was founded in 1946. The company's primary activities include research & development, production, and sale of original products, generics, and active pharmaceutical ingredients.

The company exports its products to more than 70 countries. The main markets include the European Union, Russia, and other CIS countries, as well as the USA, Canada, Japan, Vietnam, and others. 

Mildronate (Meldonium) was called one of the most famous and most exportable products in the company’s portfolio.

High-quality standards of Grindex are verified by certificates from EU GMP, RU GMP, FDA, PMDA, TGA, and other regulatory authorities. The company also adheres to the principles outlined in the Guidance for Industry ICH Q10, Pharmaceutical Quality System. 

Grindex operates in accordance with the requirements of the following standards:

Meldonium generics are manufactured by other pharmaceutical companies in Europe (Serbia, Georgia, and others), which complements the effectiveness and safety of the original preparation. 

There is also a Mildronate analog called BrainMax. It is a synergy of Mildronate and Mexidol active substances with enhanced neuroprotective, anti-hypoxic, antioxidant, nootropic, and anti-ischemic effects. Thus, it can reduce clinical manifestations of cerebrovascular insufficiency, improve cognitive functions, normalize emotional state, reduce symptoms of stress, and increase efficiency and tolerance to mental and physical exertion. 

To sum up, Meldonium (trade name Mildronate) is a metabolic modulator used to normalize the energy metabolism of cells exposed to hypoxia or ischemia. It is said to have the ability to support the energy metabolism of the heart and other organs.

It is also used by athletes to deliver better sports results. But it was named a doping substance by WADA and has been banned since 2016.

Meldonium is popular among individuals seeking to enhance their performance because it is low-toxic and does not cause severe side effects. Along with that, it has good compatibility with other medications, namely, nootropics. You can stack it with Turkesterone for better sports results. It also goes well with Semax if your aim is improved memory and focus. You can also read about safe stacking in our article, or have a lokk at the fullest Actovegin Review or Phenylpiracetam Review.

However, there are some contraindications that should be regarded before taking Mildronate. Please read the instructions and consult with your doctor prior to administering the drug.