NO boosters are myostatin inhibitors

Bodybuilding supplements that boost the concentration of nitrogen monoxide – NO for short – in the muscles are probably also myostatin inhibitors. This emerged from an in-vitro study done at the Stem Cell Research Institute in Milan, which was published in the Journal of Cell Biology. NO boosters ought to work if the basic research is anything to go by. Countless studies have shown that nitrogen monoxide is an important factor in muscle growth. But evidence from studies in which researchers have given strength athletes nitrogen-monoxide boosters has been inconclusive. It would seem that the applied scientists are missing something.

In the Italian study here, the researchers extracted muscle cells from mice embryos and exposed them in test tubes to DETA-NO, an NO donor, and L-NAME, a compound that inhibits the formation of NO.

The researchers discovered that exposure to the NO-donor stimulated satellite cells – young muscle cells that are not yet part of the muscle fibres – to take up their position in the muscle tissue. DETA-NO boosted the cells’ fusion index; L-NAME reduced it.

NT = cells that were not treated.


The NO booster worked via the cellular messenger molecule cGMP, the Italians discovered. If they deactivated cGMP with the inhibitor ODQ, then DETA-NO did nothing. If they added 8Br-cGMP, a substance that imitates the effect of cGMP, then the effect of the NO donor on the muscle cells became greater.

The figures below give an idea of the way in which the NO donor works: the substance boosts the production of follistatin in different sorts of muscle cells, and thus inhibits the production of myostatin.


It’s difficult to extrapolate from test-tube studies to reality, but not being hindered by great scientific knowledge, we’ll take a chance. The concentration of cGMP in the body probably rises the more you consume of compounds such as cyanidin-3-O-beta-glucoside, malvidin-3-O-beta-glucoside, chlorogenic acid, ginkgetin and also curcumin. These compounds are found in cherries and berries, grapes, coffee, ginkgo and turmeric respectively. [J Nutr. 2012 Jun; 142(6): 1033-7.] [J Agric Food Chem. 2005 Mar 23; 53(6): 1960-5.] [Blood Coagul Fibrinolysis. 2012 Oct; 23(7): 629-35.] [Planta Med. 2006 Apr; 72(5): 468-70.] [Vascul Pharmacol. 2007 Jul; 47(1): 25-30.]

If you combine these substances with an NO donor, they may well work better. And if you’re stacking anyway: creatine is a myostatin inhibitor…

Follistatin induction by nitric oxide through cyclic GMP: a tightly regulated signaling pathway that controls myoblast fusion.

Pisconti A, Brunelli S, Di Padova M, De Palma C, Deponti D, Baesso S, Sartorelli V, Cossu G, Clementi E.

Stem Cell Research Institute, Hospital San Raffaele, 20132 Milan, Italy.


The mechanism of skeletal myoblast fusion is not well understood. We show that endogenous nitric oxide (NO) generation is required for myoblast fusion both in embryonic myoblasts and in satellite cells. The effect of NO is concentration and time dependent, being evident only at the onset of differentiation, and direct on the fusion process itself. The action of NO is mediated through a tightly regulated activation of guanylate cyclase and generation of cyclic guanosine monophosphate (cGMP), so much so that deregulation of cGMP signaling leads to a fusion-induced hypertrophy of satellite-derived myotubes and embryonic muscles, and to the acquisition of fusion competence by myogenic precursors in the presomitic mesoderm. NO and cGMP induce expression of follistatin, and this secreted protein mediates their action in myogenesis. These results establish a hitherto unappreciated role of NO and cGMP in regulating myoblast fusion and elucidate their mechanism of action, providing a direct link with follistatin, which is a key player in myogenesis.

PMID: 16401724 [PubMed – indexed for MEDLINE]
PMCID: PMC2063553