The US/Israeli team propose a nutraceutical strategy comprising 11 agents that (between them) control lung oxidative stress, bioactivity of nitric oxide (NO) and hydrogen sulfide (H2S) and induce bronchodilation to help reduce chronic inflammation of lung airways.
The recommendations follow a review of the current body of knowledge on molecular processes underpinning the pathogenesis of asthma with a particular focus on the effects of reactive oxygen generated by nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase complexes.
Managing oxidative stress
The team note that elevated levels of bilirubin inhibited NADPH oxidase complexes in a teenager suffering from hepatitis B, triggering a temporary remission of asthma symptoms. This led them to propose the cyanobacteria spirulina as a viable alternative to bilirubin (which has marked insolubility) for oral administration as it contains similar therapeutic properties (notably phycocyanobilin (PhyCB)).
“It has been estimated that humans might need to take 15–30 grams (g) spirulina daily – or the equivalent intake of PhyCB – to achieve optimal anti-inflammatory effects. However, a small non-blinded controlled trial in adult asthmatics found that one gram daily of spirulina provided clinical benefit comparable to standard medication, and that the combination of spirulina with medication produced the best clinical outcomes,” they write.
They surmise that supplementation with N-acetyl cysteine (NAC) (600 mg 2-3 times daily) may also relieve asthma symptoms by increasing production of tissue glutathione (an antioxidant) and help counteract the pro-inflammatory effects of oxidative stress.
The review says: “In a controlled clinical study, enrolling individuals hyperresponsive to methacholine challenge, 6 days of NAC pre-treatment (600 mg three time daily) reduced baseline methacholine responsiveness by about 20%, and also blunted the ability of diesel exhaust to increase airway hyperresponsiveness.”
Corresponding oral administration of lipoic acid (LA) may further stimulate glutathione production and bilirubin in cells, as well as complement PhyCB activity. The authors point out that LA is the most clinically developed phase 2 inducer and ‘has been shown to be therapeutically beneficial in diabetic neuropathy in doses of 600 mg 2–3 times daily’.
Another compelling compound touted by the researchers is selenium which they say could be especially favourable to patients with poor baseline selenium nutrition: “Indeed, a recent meta-analysis has concluded that patients with asthma tend to have lower plasma selenium levels than controls.”
Boost NO and H2S bioactivity
The team postulates the potential value of specific nutraceuticals to boost nitric oxide (NO) synthesis, which facilitates expansion of the bronchial air passages and opposes hypertrophy and hyperplasia. For example, supplementation with high-dose biotin (10 mg, 2-3 times daily) stimulates soluble guanylyl cyclase production (sGC) while citrulline (2-3 g twice daily) promotes proper coupling of NO synthase to enhance NO performance.
“Measures which promote proper coupling of NO synthase should be doubly beneficial for asthma control, as these could be expected both to enhance NO production and bioactivity, and to decrease production of superoxide,” they note.
Furthermore, additional NAC supplementation (600 mg 2-3 times daily) and taurine (1-3 g twice daily) can optimize lung hydrogen sulfide (H2S) production that also complements the activity of NO and protects sGC from oxidative inhibition.
The review states that one 7-day study revealed oral pre-treatment with taurine decreased hyperresponsiveness to the ‘bronchoconstrictor 5-hydroxytryptamine, while also decreasing eosinophils and markers of oxidative stress in bronchoalveolar lavage fluid’. These effects were similar to those observed in the same group in response to NAC supplementation.
Improve lung function
Oral administration of glycine (5-10 g, 2-3 times daily) and magnesium (Mg) (100-200 mg, twice daily) is posited as an effective therapeutic measure to improve lung function.
The researchers note that both compounds facilitate bronchodilation through modulating calcium influx. Glycine-induced membrane hyperpolarization opposes calcium influx and activates bronchodilation, while a small increase in intracellular Mg ‘may modestly blunt the ability of calcium influx to activate [calmodulin-dependent myosin light chain kinase] MLCK’ that promotes contraction.
They add that glycine complements NAC in raising tissue glutathione levels, so has broad potential as a nutraceutical treatment.
In conclusion, the researchers stress that further clinical evaluation is necessary to substantiate the recommendations as the proposed measures are largely speculative. Nevertheless, they maintain the practical potential of the agents as adjuvants, however marginal, should not be overlooked and posit functional foods or beverages as possible future deliver mechanisms.
Source: Journal of Asthma and Allergy
Published online: doi.org/10.2147/JAA.S307549
“Review – Nutraceuticals Can Target Asthmatic Bronchoconstriction: NADPH Oxidase-Dependent Oxidative Stress, RhoA and Calcium Dynamics”
Authors: Mark F McCarty, James J DiNicolantonio, Aaron Lerner