STUDY: Contradictory new data on nitroglycerin for tendinitis
Nitroglycerin has a colourful history, from powering dynamite to treating cocaine side effects, angina, and anal fissures. Most people don’t even know that it has medical uses other than heart pain.
In biology, nitro is quickly converted to nitric oxide (NO; not to be confused with nitrous oxide, which is N2O). The NO is actually the active ingredient, and a powerful vasolidator … maybe anti-inflammatory … maybe analgesic … and, most importantly, maybe a tendon builder. So maybe it’s good tendinitis medicine?
We’ve needed some superior science on this for ages, and we finally just got some from Kirwan et al, a nicely controlled test of nitroglycerin ointment done the way most of us would do it: smear some on daily for a while. What have we learned from their science-ing?
| title | Topical glyceryl trinitrate (GTN) and eccentric exercises in the treatment of mid-portion achilles tendinopathy (the NEAT trial): a randomised double-blind placebo-controlled trial |
|---|---|
| journal | British Journal of Sports Medicine |
| Volume 58, Number 18, Sep 2024, 1035–1043 | |
| authors | Paul D Kirwan, Trevor Duffy, and Helen P French |
| links | publisher • PubMed • PainSci bibliography |
Kirwan et al. tested topical nitro on a few dozen Irish folks at a Dublin hospital. They compared nitro to an “aqueous cream, which contained no ingredients that would aid in tendon recovery.” (And yet you can easily find examples of cranks making the oversimplified claim that tendons need to be hydrated. 🙄)
Everyone also did the same exercise program for six months: the Alfredson protocol (predictably), a bunch of calf exercise made fiddly by doing them the eccentric way (loaded elongation). “It is known” that the Alfredson protocol is no better than simpler weighlifting. The authors reference that evidence from 2015, explaining that it was “published after this trial was designed.” (So this trial took at least a decade to pull off? Wowsers!)
All that exercise, plus time, means that everyone was likely to get better, and they did. But did nitro-smeared heels heal faster?
The answer was … no difference. An utterly negative result on its face. Nitro conveyed no advantage whatsoever.
It did convey some headaches though, which is a well-known side effect. (It’s also a potent migraine trigger in people with that vulnerability.)
This is the GTN ointment that was used in the study. Availability of nitro ointments and patches is patchy around the world. For instance, “it was not possible to use altered or cut transdermal GTN patches for the purpose of this trial, in line with European Union regulations.” Most nitro ointments are for anal fissues, and have re-for-rectal names like Rectogesic, Repane, and (on-the-nose) Recto-Relief. (Get a load of the cheesy anal-pain graphics here! It also includes a fully illustrated guide to usage, and I do mean FULLY.) You can use the made-for-butts nitro products on your tendons. It is exactly the same stuff.
This is why one study is never enough
This new result is the opposite of another quite old result, from a similar 2004 trial, also fairly rigorous. To be clear:
- In 2004, Paoloni conducted a good quality trial with a strongly positive result. 👍🏻
- In 2024, Kirwan conducted a good quality trial with a strongly negative result. 👎🏻
What gives? Kirwan et al. speculate that it could be chalked up to either their different outcome measures and/or dosage. Paoloni et al. used more nitro, from a patch, and reported both more benefit and more harm: more tendinitis relief, more headache grief! This could be tidy example of how a relatively small detail might make all the difference, and explain how two good quality trials can produce completely different results.
That is about as simple and clear as a graph of trial results can get! Even where the GTN and the placebo differ, the gap is much smaller than the error bars. Just absolutely no difference. But — and this is THE question about this study — would a higher dose of GTN have pushed that blue line higher than the pink? That’s not just speculation: that’s what Paoloni et al. reported in 2004.
The conclusion of the new study is less pessimistic than its results. On the one hand, “our results do not support the use of topical GTN ointment in treating Achilles tendinopathy.” No, indeed, they do not. And despite using ointment instead of patches, they had reasons to think it was enough. Ointment “has been shown to be as effective as patches,” based on a study of anal fissures. But butts probably don’t heal the same as heels, so that’s hardly conclusive.
And so, on the other hand, maybe this new trial was negative just because ointment did not deliver enough nitro:
In light of our incomplete understanding of tendon pathophysiology, the study of GTN is warranted, as basic science, animal and human studies have confirmed NO as an important chemical messenger in tendon pathology and repair.
If the only two good trials were both negative, I would say “case probably closed.” But as it is, I think it would be a mistake for a careless skeptic to point to this paper and scoff at nitro for tendons. I think this is an unusually legitimate example of “more study needed.”
See my guide to Achilles tendinitis for some more information (and colour) about topical glyceryl trinitrate.