Fish Oil as Myostatin Inhibitor

I was researching Myostatin and somehow ended up here…

That is pretty much it; weird, huh?

Researching how to block the most potent inhibitor of muscle protein synthesis, of which pure inhibition is probably more anabolic than any testosterone mimetic in existence. Then I end up back at fish oil, somehow before Preparing for an FDA Audit.

The realizations below kinda blind sided me, and articles are best written when I had no prior preparation into them. Therefore, below I will explain how you can joke around about fish oil being a ‘myostatin inhibitor’ although its quite detract from the truth. :)

(Note: The featured image of this article is a fish, the Medaka, suffering from a Myostatin deficiency. All species get jacked without Myostatin)

Direct interventions with Fish Oil

Direct intervention studies that look at fish oil and muscle protein synthesis in humans include:

  • Otherwise healthy elderly men, consuming 4g Lovaza (1.86g EPA, 1.5g DHA) for 8 weeks [x]
  • Same dose and product in healthy young and middle aged people (rules out age) [x]
So, two. Not too many, but there exists no counter evidence to suggest that fish oil doesn’t do as the above says. Its preliminary, but its pretty good evidence.
There are some animal models which suggest similar effects. Bovine [x] and mice. [x] [x] The human intervention studies and the animal models all suggest the same thing with fish oil in regards to muscle building and is the same as esa arizona.
  • Fish oil, per se, does not increase protein synthesis rates
  • Fish oil seems to be pretty damn good at augmenting protein synthesis rates from leucine
The pathway leucine acts on, the mTOR/Akt signalling pathway, seems to be more powerful under periods of excess omega-3 fatty acids. The bovine study above is a good mechanistic study.

As far as I know, no mechanisms have been elucidated in academia as of yet. I offer my thoughts, and given the intro to this article you can probably guess where this is going.

Possible Mechanisms – SMADs

Fish oil supplementation, or technically EPA and DHA (the components), have been shown in two animal studies to beneficially influence SMAD signalling.

The first study noted that, in renal tissue, there was increased expression of SMAD7 (beneficial to muscle growth) and suppression of SMAD2 (one of the basic anti-myogenic signals). The dose was 0.3g/kg daily fish oil via gavage (into stomach).

The second study looked at rats under conditions of cardiac damage, and found that fish oil (at a dose of EPA + DHA being 1% of the diet by calories) preventing the SMAD2/3 complexes from entering the nucleus and hindering protein synthesis.

Sadly, there are not many more studies that look at SMAD signalling from fish oil supplementation. The intervention studies show benefit, the manner in which they do this is similar to Myostatin inhibition, and there appears to be preliminary evidence that fish oil acts on the same pathway as Myostatin inhibitors (just a whole lot less potent).

I’ll explain WTF the above meant now…

SMAD signalling, the really basic Tl;Dr

There are 7 SMADs, these are just proteins floating around in the cytoplasm of a cell.

When myostatin ‘suppresses’ protein synthesis, it does so through SMADs. The myostatin protein is huge and can’t actually get into the cell, so in order to work on the nuclear it has to work through other proteins (a lot like insulin). Its a chain of events, but you can break the chain at any point if you wish.

The main ones of concern are the basic SMADs (2,3 are most relevant, but also 1,5,8) that suppress protein synthesis. Once they get the signal, they will just group together and bind with SMAD4. The cluster of those SMADs (everything but 6 and 7, with 4 playing a prominent role) can go into the nucleus and hinder protein synthesis.

SMAD 6 and 7 are inhibitory. If they jump into the complex then the complex cannot hinder protein synthesis anymore. This is why above I liked it when SMAD7 was increased, more inhibition. So basically:

  • SMAD6 and SMAD7 are the muscle loving crime fighting duo
  • SMAD4 is the leader of the muscle haters
  • All other SMADs are his minions

Chronic fish oil ingestion seems to change some SMADs to a more favorable state to build muscle. This is consistent with Myostatin in the sense that, unless you pharmaceutically increase the levels of Myostatin in the blood, normal increases in Myostatin do not increase protein synthesis per se, they require but potentiate other sources of anabolism. [x] (Although it should be noted that, not related to fish oil, Myostatin can do additional mTOR suppression; its bloody powerful [x])

Tl;Dr Bullet Points

  • Fish oil does not increase protein synthesis, but it promotes protein synthesis induced by amino acids
  • The way it MAY do this is through beneficially influencing SMADs, which are how Myostatin acts on the nucleus
  • The dose required to do this orally is very doable. As low as 3 grams combined EPA+DHA has benefit
  • You can potentially get away with calling fish oil a Myostatin inhibitor, and I expect supplement companies to begin marketing it as such as soon as they realize this
It should be noted that I’m not retarded enough to claim fish oil gives you Gainz like a Myostatin deficiency or like true Myostatin inhibitors (Follistatin, FLRP-II, etc.) If you want to know the degree of results, look at the above two human studies, and you can probably get a bit more benefit than those seen.

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  1. Youknowutimsayin says:

    So… what do I need to take with the fish oils to get them gainz?

  2. akharon says:

    3g/day seems like quite a bit, financially at least. What do you find is the best bang for the buck with fish oil supps?

  3. JoshuaJ says:

    Interesting read. Do you think 2grams of fish oil along wtih BCAA’s as they include leucine can help to inhibit myostatin? I’ve done quite a bit of research on myostatin on my blog. I haven’t come across anything for fish oils and reducing myostatin. Would appreciate your thoughts as I might try the fish oil and BCAA stack if you think its a good idea.

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