Experience with Meldonium

Supplements
#1

Anyone have experience using meldonium? I used it for a while and seemed to have slightly better endurance while running…

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#2

https://journals.sagepub.com/doi/full/10.1177/2397847320915143

would make sense due to similarities to L-Carnitine

How has your experience been with it and what was your rationale for using it?

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#3

Lol it’s like saying, anyone tried EPO?

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#4

Is it as effective as EPO?

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#5

Re EPO - no idea, but the safety profile is better. You don’t have to worry about blood clots. Eastern bloc/Russian countries seem to have an idea on which compounds can improve performance.

I tried it to see if I could have better workouts - seemed to help me maintain better pace on longer runs, but that’s it.

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#6

Does it only help with endurance training or could it help with anaerobic?
Also what brand is good to buy it ?

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#7

also what dosing regimen do you use

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#8

Thats the understatement of the decade :grin:

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#9

From my reading it’s more for improvement in aerobic activities, but I could be wrong. Grindex makes it - you can get 60 capsules from Amazon for around $30 - I took 500mg per day.

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#10

I’ve read that is has benefit for heart function as well, so I was looking into taking it for that. But I wonder if there would be any drawbacks from taking it at a young age(24). Although it seems like taking L-Carnitine or Nitric oxide

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#11
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#12

Ha - may skip doing another meldonium trial…

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#13

It is very strange that this molecule has not received the attention it deserves.

I’ll put here a short ai review for meldonium. And I have even translate some russian article which you can not find on pubmed. As it mostly russian molecule, there are several local studies, not known abroad.
Anyone who have a heart conditions needed medical supervisions have to look closer to this substance. And if you do some long cardio exercises - also look for it. But - maybe (just maybe!) it can can affect short anaerobic exercises on maximum strength. So if you do powerlifting with 1-3 repetitions - maybe its not your thing. Its beneficial if you like running, skiing, swimming and so on, but - if you like opposite as well) I mean… If you drink, and/or use some recreational drugs, it can help to maintain your heart during any stresses. Psychological ones included. So any work stresses too. Everything which makes your heart pumps too hard for too long - will be easier with meldonium (mildronate)

I do 1-2 times per year 1 month course of it. But now, after I did some researches with ai, I think that maybe its even more interesting and needs longer courses, maybe 2m on, 2m off or similar, maybe even 2 times per day (but not more, there is some preclinical data in mice, that doses, equivalent to human 3-4g per day can cause fat in a liver, as redistribution of excess energy to fat depo starts)

Meldonium (Mildronate): what is established, and what the Russian-language literature suggests

Meldonium is a metabolic modulator rather than a stimulant. It inhibits γ-butyrobetaine hydroxylase, reduces carnitine availability and therefore limits mitochondrial entry of long-chain fatty acids. This shifts energy production toward glucose oxidation, which generates more ATP per unit of oxygen under ischemic conditions. It may also reduce accumulation of potentially harmful long-chain acylcarnitines and improve nitric-oxide-dependent endothelial function. Its best-supported clinical role is as an adjunct in ischemic heart disease, not as a proven longevity drug.

Strongest clinical evidence

MILSS I was a 12-week, randomized, double-blind, placebo-controlled trial involving 512 patients with stable angina and exercise-limiting ischemia across 72 centers.

  • Meldonium 1,000 mg/day — 500 mg twice daily — increased total exercise time by 35.18 ± 53.29 seconds from baseline.
  • Placebo produced a change of −7.10 ± 81.78 seconds.
  • The difference was significant at p=0.002.
  • Doses of 100 and 300 mg/day were not significantly effective, while 3,000 mg/day was not better than 1,000 mg/day.

This is the clearest evidence that meldonium can improve exercise tolerance when myocardial oxygen supply is the limiting factor.

Interesting longer-term cardiovascular data

A small Russian study randomized 50 patients with hypertension, left-ventricular hypertrophy and stable ischemic heart disease to ramipril alone or ramipril plus meldonium 500 mg twice daily. Meldonium was continuous for six months and then given for two months on/two months off, with a total follow-up of 24 months.

At 24 months:

  • Left-ventricular mass index fell by 13.0% with ramipril plus meldonium versus 9.0% with ramipril alone.
  • E/A, an older Doppler measure of diastolic filling, increased from 0.98 to 1.59 versus 0.97 to 1.24.
  • Ejection fraction increased by 8.8% versus 4.0%.
  • Carotid intima–media thickness decreased by 19.6% versus 13.3%.
  • Brachial flow-mediated dilation increased 3.9-fold in the combination group; improvement in the ramipril-only group plateaued after an initial 2.7-fold increase.

These results suggest possible additive effects on cardiac remodeling, diastolic filling and endothelial function. However, this was a very small, apparently non-blinded study, and its diastolic assessment did not use modern parameters such as e′, E/e′ or left-atrial volume.

Arrhythmia and heart-failure signals

In the 42-day INDIKOR observational study, 1,128 patients with heart failure and metabolic disorders were analysed; 897 received meldonium 1,000 mg/day and 231 received standard therapy alone.

At follow-up:

  • Recorded arrhythmias: 5.7% vs 14.3%.
  • Conduction blocks: 13.6% vs 21.1%.
  • Any abnormal ECG finding: 41.1% vs 49.8%.

Quality-of-life and fatigue scores also improved more in the meldonium group. These are noteworthy signals, but INDIKOR was not randomized, so treatment selection and other confounders may explain part of the difference.

A smaller randomized post-myocardial-infarction study involving 67 patients reported fewer supraventricular extrasystoles (p=0.002) and fewer paroxysmal rhythm disturbances (p=0.001) after 12 weeks of meldonium, although the abstract did not provide raw event counts.

Metabolic findings from Russian studies

A 12-week study of 100 patients with heart failure and type 2 diabetes added meldonium 1,000 mg/day to standard therapy. The reported changes were:

  • HbA1c: 7.4% → 6.5%, versus 7.1% → 6.9% in controls.
  • Triglycerides: 2.6 → 1.9 mmol/L, versus 2.6 → 2.4 mmol/L.
  • VLDL cholesterol: 1.18 → 0.86 mmol/L, versus 1.20 → 1.10 mmol/L.

These figures are impressive, but the study was small, not placebo-blinded and has not been independently replicated. ([Медицинские журналы и статьи

In another 12-week study of 70 patients with type 2 diabetes and peripheral neuropathy, adding meldonium was associated with:

  • Triglycerides: −17.7%.
  • Number of patients with hypertriglyceridemia: −48%.
  • A nonstandard “metabolic index”: −46.75%, versus approximately −11.9% in controls.

However, the treatment groups were poorly balanced at baseline, and the “metabolic index” was not HOMA-IR. These results should therefore be treated as hypothesis-generating.

There is also negative evidence: in 45 patients with hypertension and prediabetes receiving 1,000 mg/day for three months, HbA1c remained essentially unchanged — 6.29% to 6.27% — and triglycerides did not improve significantly. Meldonium therefore does not appear to be a reliable glucose-lowering drug in every population.

Bottom line

Meldonium has:

  • a well-established metabolic mechanism;
  • credible randomized evidence for improved exercise tolerance in ischemic angina;
  • interesting but less rigorous signals for cardiac remodeling, endothelial function, arrhythmias, insulin resistance and triglycerides;
  • no large cardiovascular-outcome trial showing fewer myocardial infarctions, strokes, heart-failure admissions or deaths;
  • no human evidence that it extends lifespan.

In my view, meldonium is scientifically more interesting than its near-absence from Western medicine would suggest, but the Russian results need modern, independently replicated, double-blind trials before they can be treated as definitive.

I can add - its true for almost all of our most used molecules (if not all).

Meldonium_Ramipril_24_month_study_English_translation.pdf (277.6 KB)

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#14

It certainly does sound fascinating. I’m putting this on my list of compounds to keep an eye on!