Long-term mildronate treatment increased Proteobacteria level in gut microbiome, increases anxiety and causes dysbiosis

[Lokzo]

Long-term mildronate treatment increased Proteobacteria level in gut microbiome, and caused behavioral deviations and transcriptome change in liver, heart and brain of healthy mice​

Artem P Gureev 1, Ekaterina A Shaforostova 2, Inna Yu Vitkalova 3, Irina S Sadovnikova 2, Yulia I Kalinina 2, Vadim R Cherednichenko 2, Karina A Reznikova 2, Valeria V Valuyskikh 2, Vasily N Popov 3
Affiliations expand

• PMID: 32389661
• DOI: 10.1016/j.taap.2020.115031

Abstract​

Mildronate is a cardiac and neuroprotective drug that is widely used in some countries. By inhibiting carnitine biosynthesis, mildronate impairs the fatty acids transport into mitochondria, thereby decreasing the β-oxidation intensity. Since 2016, it has been prohibited by the World Anti-Doping Agency (WADA). However, the information on its safety and its influence on the athletes' health is scarce. There are no published studies on whether mildronate-induced long-term metabolism "rearrangement" may cause negative effects on high-metabolic-rate organs and on the whole organism. Here, we demonstrate that long-term mildronate treatment of healthy mice induced global metabolism change at the transcriptome level in liver, heart, and brain. Mildronate treatment also induced some behavioral changes such as anxiety-related behavior and diminished explorative behavior. We also found that mildronate induced a dysbiosis, as manifested by an increase in Proteobacteria level in gut microbiome. At the same time, the absence of a statistically significant increase in mouse strength and endurance procedures suggests that mildronate effect on productivity is negligible. The sum of our data suggests that long-term treatment of healthy mice with mildronate induces dysbiosis and behavioral deviations despite the effectiveness of mildronate for cardiac and neurological diseases. Thus, we suggest that long-term mildronate treatment is undesirable or at the very least should be accompanied by prebiotics treatments, but this issue should be studied further.

 

[ww3not4me]

And yet so many athletes swear by it.

I was taking 50 units of slow acting and 50 units of fast acting insulin per day. Once I added Mildronate it cut my blood sugar almost in half in 2 days time. I added Mexidol to that and it allowed me to cut my total insulin usage from 100 units a day down to 40 units per day and getting better. That is with out any dietary changes.

Too early to tell much at this point. I will let you know more when I know more! I suspect that both of these drugs are going to be such that your mileage may vary depending on what is wrong with your mitochondria and the rest of your metabolism both in peripheral tissues and the brain!

Between Mildronate and Mexidol I think the Mexidol which is based off of Vitamin B6 molecule has made the bigger difference between the two in my case.

 

[youngsinatra]

And yet so many athletes swear by it.

I was taking 50 units of slow acting and 50 units of fast acting insulin per day. Once I added Mildronate it cut my blood sugar almost in half in 2 days time. I added Mexidol to that and it allowed me to cut my total insulin usage from 100 units a day down to 40 units per day and getting better. That is with out any dietary changes.

Too early to tell much at this point. I will let you know more when I know more! I suspect that both of these drugs are going to be such that your mileage may vary depending on what is wrong with your mitochondria and the rest of your metabolism both in peripheral tissues and the brain!

Between Mildronate and Mexidol I think the Mexidol which is based off of Vitamin B6 molecule has made the bigger difference between the two in my case.

Do you eat significant amounts of dietary fats?

 

[ww3not4me]

Not really. Even when I am doing low carb I never actual do Keto were fat intake is insane. Gallbladder pain keeps me very honest with the fat intake.

That said growing up as a child my mom cooked with vegetable oil and feed us margarine. Up until about about a year ago I was using seed oil for cooking namely grape seed oil. So about a year ago I cut out PUFA's.

In 2018 I had lost 79lbs. and was off all diabetes medicines. Then in March of 2020 I got SARS-CoV-2 and I had it bad. Thought it was going to kill me. Doctors did nothing. Suffered long Covid-19 and my blood sugars went out of control and have never improved. My endocrinologist tried me on must of been 8 different drugs besides the Metformin, Starlix, and Insulin but they all caused terrible side effects.

So I decided to try Mildronate since it works on the Mito and it helped and then I added Mexidol and it helped as well. I have to prepare all of my food because I am allergic to corn, wheat, soy, laytex, peanuts and tree nuts so it all home cooked food for me.

 

[youngsinatra]

Not really. Even when I am doing low carb I never actual do Keto were fat intake is insane. Gallbladder pain keeps me very honest with the fat intake.

That said growing up as a child my mom cooked with vegetable oil and feed us margarine. Up until about about a year ago I was using seed oil for cooking namely grape seed oil. So about a year ago I cut out PUFA's.

In 2018 I had lost 79lbs. and was off all diabetes medicines. Then in March of 2020 I got SARS-CoV-2 and I had it bad. Thought it was going to kill me. Doctors did nothing. Suffered long Covid-19 and my blood sugars went out of control and have never improved. My endocrinologist tried me on must of been 8 different drugs besides the Metformin, Starlix, and Insulin but they all caused terrible side effects.

So I decided to try Mildronate since it works on the Mito and it helped and then I added Mexidol and it helped as well. I have to prepare all of my food because I am allergic to corn, wheat, soy, laytex, peanuts and tree nuts so it all home cooked food for me.

Sorry to hear that. Yeah, COVID can severely disrupt the whole organism, whether it‘s the cardiovascular system, glycemic control, CNS functioning and so on, even in relatively healthy people.

If it helps your blood sugars, then I‘d be okay with mildronate, but pyrucet (from Idealabs) might work in a similar fashion and many have reported drastically improved glucose utilization and control with pyrucet usage.

 

[ww3not4me]

Sorry to hear that. Yeah, COVID can severely disrupt the whole organism, whether it‘s the cardiovascular system, glycemic control, CNS functioning and so on, even in relatively healthy people.

If it helps your blood sugars, then I‘d be okay with mildronate, but pyrucet (from Idealabs) might work in a similar fashion and many have reported drastically improved glucose utilization and control with pyrucet usage.

I will definitely look into that!!