Humming stimulates nitric oxide production

Breath: the New Science of a Lost Art, by James Nestor opened my eyes to the power of breathing and its ability to influence our overall health. The book is an absolute must-read. I recommend incorporating at least some of its suggesstions into your daily life - it has helped me a great deal.

I wanted to highlight a connection between Nose Songs, one of the practices detailed in Breath, and the physiology of blood vessels.

Nose songs simply mean humming to a song with your mouth closed and breathing through your nose while doing so. Nestor asserts that doing this for 5 minutes a day can increase the nitric oxide (NO) in your nasal passages 15-fold. Nestor cites research and in the public domain there is some science backing up this claim: here, here, and here.

A few open questions exist here. Is this 15-fold increase transient? How long after performing the humming does the increased NO synthase activity last for?

But, why is NO important? This gas vasodilates vessels, and has anti-inflammatory and anti-coagulatory properties. Simply, it keeps vessels open and free of clots. This is particularly relevant in people who have hypertension and run the risk of atherosclerotic plaques clogging their arteries.

Additionally, there is a neat connection between NO and free radicals that are generated in patients with atherosclerosis (~40% of US adult population). In atherosclerosis, LDL molecules get oxidized and trigger a chronic inflammatory response that lead to plaque formation in blood vessels and stress on endothelial cells that line the vessels. These stresses and resulting turbulent blood flow (the vessel is no longer ‘smooth’), trigger the production of reactive oxygen species (ROS) and inflammation proteins by endothelial cells. ROS damage DNA and lead to cell death. Natural anti-oxidants (e.g., glutathione) quench these free radicals, but we only have a finite supply of these molecules. Once we run out of antioxidants, ROS wreak havoc in our bodies increasing the likelihood of disease. Specifically, increased ROS increases the probability of developing cancer (DNA damage leads to mutations leads to increased probability of cancer) and vessel blockages (cell death and DNA damage continues to trigger immune response which leads to more inflammation and more vessel occlusion). ROS are produced by NADPH Oxidase and NO is produced by NO Synthase. Both of these enzymes share the same substrates* but produce completely antagonistic effects! Both NADPH Oxidase and NO Synthase take in oxygen and NADPH but turn them into entirely different products, ROS and NO respectively. Since these enzymes use the same substrates, producing more NO means making less ROS. It stands to reason that otherwise healthy people who engage in activities that increase NO and thereby decrease ROS will have less inflammation and likelihood of cancer in the tissues that are affected by their activity. For humming, this is probably limited to tissues directly involved in humming such as the nasal epithelium, sinuses, larynx, upper respiratory tract, and some respiratory vasculature and lung tissue.

How can we do favor NO production over ROS? We can either a) increase the amount of NO Synthase, b) decrease the amount of NADPH Oxidase, or c) increase the affinity of the substrates for NO synthase relative to NADPH oxidase. From my understanding of biochemistry, given that the substrates are the same, without alterting the structures of the enzymes we cannot alter their affinities for the substrates. But, option A and B are both valid options and indeed, in humming, we likely take option A. Are there other behaviors or activities that lead to option A or option B taking place?

Humming raises NO levels thereby decreasing ROS levels. There is no evidence to suggest these effects are systemic. The NO increase and ROS decrease is likely limited to the nasal passages, sinuses, and maybe some of the respiratory vasculature. Could humming be protective against and/or help treat pulmonary hypertension (PAH)? I would say yes. What is the magnitude of this intervention though? Unsure.

Many PAH drugs act on on the NO pathway with the net effect of increasing NO Tettey, 2021 supporting humming in this condition. In a very small sample size of five patients, inhaled NO decreased pulmonary vascular resistance by 34% and mean pulmonary artery pressure by 17% here. A review article on the utility of vasodilators like NO in treating PAH notes that “drugs that taret vasodilation in the pulmonary but not systemic circulation … provide promise in future therapeutics for PAH”. Why limit ourselves to drugs? We can also think about behavioral and activity interventions like humming too.

NO can inhibit the replication cycle of the SARS virus as seen in this paper. This study was done in cell lines, and has a number of other limitations. But, it raises an interesting question: Can routine humming help protect us from being infected by respiratory viruses?

* NO synthase requires arginine as a cofactor. Does increasing the concentration of arginine help NO synthase outcompete NADPH oxidase?