Is Asthma a Dietary Disease – Part 2


To my knowledge, to date there has been only one randomised controlled trial (RCT) of dietary modification in asthma. Lots of studies have looked at relationships between dietary intake and the occurrence of wheeze, but only one group has taken patients and asked them to eat a specific diet in order to see what happens to them. In part that may be because adequately powered (i.e. large) randomised controlled trials are time-consuming and expensive: they need whole teams of people dedicated to their execution and analysis, and that requires substantial amounts of funding as well as someone with considerable research experience and an interest in the field to take the lead.

About the study (here’s the technical bit, for those who are interested in critical appraisal – otherwise skip to the end):

Lisa G. Wood et. al from the Centre for Asthma and Respiratory Diseases and Nutraceuticals Research Group at the University of Newcastle, Australia, have carried out a single-site RCT comparing outcomes for high and low antioxidant diet groups (1). The low antioxidant (LAO) diet group (91 asthmatic adults) were advised to consume three or less portions of fruits and vegetables per day, while the high antioxidant (HAO) diet group (46 asthmatic adults) consumed seven portions. In addition, after 14 days the low antioxidant group were subdivided into two, with one group receiving a lycopene supplement in the form of tomato extract, and the other receiving a placebo (which explains why there were twice as many subjects in the low antioxidant group). The study lasted for 14 weeks, and the stated primary outcome measure was the percentage of neutrophils (a kind of white blood cell) in the sputum at 14 weeks. Other outcomes looked at were time to exacerbation, spirometry results (% predicted FEV1 and % predicted FVC), plasma CRP, IL-6, TNF-alpha and carotenoids, Asthma Control Questionnaire results, sputum IL-8 and 8-isoprostane concentrations, sputum neutrophil elastase activity and exhaled nitric oxide.

Subjects were excluded from the study if they had had a recent respiratory tract infection or asthma exacerbation, or had unstable asthma, had recently changed their maintenance therapy, were current smokers or were using vitamin supplements. No differences in baseline characteristics were observed between the HAO and LAO groups.

Participants were allocated to groups by computer-generated random sequence, and the initial group allocation was concealed from clinical recruitment staff until the randomisation code was received. Subjects were told they were taking part in a study examining diet and asthma, but were blind to the hypothesis being tested (to reduce reporting bias). Clinical staff were blinded to the treatment with tomato extract or placebo.

80% of subjects were compliant with their allocated diet, as measured by 24 hour food recall, and 85% were compliant with taking their pills. Non-compliant patients were excluded from the per-protocol analysis but not the intention-to-treat analysis. 79 of 104 subjects completed the trial, and all were accounted for at the end.

After 14 days the LAO group had a significant fall in plasma lycopene and carotenoid concentrations, a significant increase in sputum IL-8 and a significant decrease in sputum % eosinophils. The HAO group had an increase in plasma lycopene and other carotenoids, and a significant decrease in sputum eosinophil count. Subjects consuming the LAO diet had a lower % predicted FEV1 and % predicted FVC than those in the HAO groups.

However after 14 weeks there were no differences observed in lung function or airway inflammation between the HAO and LAO diet groups. There were no differences in any key outcomes between the LAO/extract and LAO/placebo groups.  A significantly greater median plasma high-sensitivity CRP was seen in the LAO group at the final visit compared with baseline (indicating increased systemic inflammation).

A significant difference in time to exacerbation was seen between the LAO group (25 of 91 – 27.5% before 14 weeks) and the HAO group (9 of 46 – 19.6% before 14 weeks), such that LAO subjects were 2.26 times as likely to exacerbate as HAO subjects (95% CI: 1.04, 4.91, p=0.039).

No significant difference was observed in the primary outcome measure, and it may reasonably be asked why percentage sputum neutrophils was chosen as the primary outcome measure in the first place. In fact the % neutrophils decreased by 4.1% in the HAO group and increased by 3.7% in the LAO group, which is in the direction that would be expected if the hypothesis were true, but the difference did not reach significance because the study was inadequately powered (i.e. too small). For 80% power to detect the expected mean change in sputum % neutrophils of 15 +/-20 between placebo and extract groups, 29 subjects per group needed to complete the trial, and in fact only 23 in each group did.

One last comment: 24 hour recall may not be the best way to monitor dietary compliance, as it is strongly subject to bias. Compliance over the course of the study was not reported (for example was it greater at the start?), and no stratification according to dose-response was carried out. The content of the remainder of the diet was also not analysed.

What does all this mean?

Essentially, while a good effort, this trial was too small to detect statistically significant results in its primary outcome measure. The significant result re. time to exacerbation supports the author’s conclusions that “modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole food interventions are most effective“. However this conclusion may be too sweeping a statement for the limited results of a single small RCT.

For such conclusions to become meaningful in clinical practice, they need to be drawn from multiple studies that all generally find the same thing. Larger studies add greater weight to the conclusions, as significant differences are more likely to be found. We should not dismiss the limited findings of this study out of hand, but it does need to be repeated.

Once multiple studies have been carried out the results can be pooled in a systematic review +/- meta-analysis. I searched the Cochrane Database of Systematic Reviews and found reviews of the effects of specific supplements (vitamin C, vitamin E, selenium) on asthma outcomes (equivocal, at best), and reviews relating to the benefits of weight loss and alternative formula milks. No review has so far been written on whole-food dietary interventions.

It seems likely that such interventions would be demonstrated to have an effect, to the extent to which compliance with the prescribed diet could be achieved, if sufficiently powered studies are carried out in the future. In the meantime dietary advice to asthmatics must be based on incomplete evidence. Highlighting the likely role of food-derived antioxidants in asthma pathogenesis should however form part of a comprehensive patient education program, on the basis of the precautionary principle and the fact that it will, at the very least, do no harm.

Finally…

Meanwhile there are many anecdotal accounts of individuals improving their asthma symptoms through dietary change out there on the internet. Before the internet, we would never have been aware of these people, and while their stories hardly constitute rigorous scientific evidence, their increasing numbers should cause scientists to prick up their ears and wonder what is going on. At the very least, they should add weight to the growing demand for well-designed trials of dietary interventions in asthma, and many other conditions too.

Here are a few examples I found while Googling about:

Chad Sarno – Raw Chef

The Best of Raw Food: Testimonials

Curing asthma – Roe Gallo’s story

Raw Glow: Cecilia Kinzie’s Story

These are all examples of people whose asthma was greatly improved or cured by switching to a raw food diet. It should be noted that this is a fundamentally different dietary change compared to increasing your portions of fruit and vegetables from three to seven. Raw fooders commonly consume upwards of 15-20 portions per day, none of which have had their nutrient content reduced by cooking, and they also do not consume all sorts of other things which may trigger asthma or allergic reactions, such as eggs, cow’s milk, soya or gluten. As far as I am aware, nobody has ever formally studied the impact of such radical dietary change on asthma outcomes, but is seems reasonable to hypothesise that if small changes produce small but positive results, then larger changes will produce greater positive results – possibly even a cure. If the raw food movement’s basic belief is correct that the natural diet of human beings should comprise of mainly (say, more than 90-95% of total calories) whole raw plant foods, then this makes theoretical sense too. Our bodies evolved to thrive on a continual input of high levels of phytonutrients, and they need them to function properly. Take them away and we get sick. Simple, but as yet unproven. I will leave these thoughts with you, but if you suffer from asthma and/or allergies, I would encourage you to give it a try. You have nothing to lose and everything to gain.

References:

1 – Manipulating antioxidant intake in asthma: a randomized controlled trial. LG Wood et. al. American Journal of Clinical Nutrition 2012. doi:10.3945/ajcn.111.032623

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