By Dr. Daniel Aronov
On average, children get about 8 upper respiratory tract infections per year. Most of which involve a cough which can be a nuisance. It can ruin the child’s sleep and the parents sleep and it can also be very distressing for the parents. A survey found that one of the common fears about their child’s cough is that they may die from asphyxiation. It’s no wonder then, that we spend a fortune on cough medications. In Australia alone, we spend $67 million per year on over the counter cough medications for kids. Yet, almost all guidelines and drug regulators warn against using them because they don’t work and they may be harmful. the Australian therapeutic guidelines, the Royal children’s hospital guidelines, the American Academy of Paediatrics guidelines, the FDA and the TGA, to name a few, all recommend against using cough medicines in kids under 6 years of age. So is there anything else we can use to combat cough in kids? Some cultures have an age-old tradition of giving honey to treat coughs, and believe it or not, honey as a treatment for cough has been tackled in the scientific literature 3 times! This week, we look at the evidence.
By far, most of the over-the-counter cough medications have dextromethorphan as their active ingredient: Robitussin, Dimetapp (cough, cold and flu), Vicks, Codral (Cold&Flu and cough), Bisolvon, Mucinex, and others.
Occasionally, like in Benadryl, Diphenhydramine is the antitussive ingredient.
RCT 1 – (Paul, 2007)
The first of our three randomised controlled trials compared honey, to dextromethorphan to usual care (doing nothing). It was done in Pennsylvania in the United States and was published in 2007 in the Archives of Paediatric and Adolescent Medicine.
They recruited anyone between the ages of 2 and 18 who presented to a single pediatric clinic in Pennsylvania with a cough that was due to an upper respiratory tract infection, having been present for less than 7 days.
All three of these RCT’s were just a one-day study. They did a cough survey on the day they presented to their doctor, then that night they got the honey pr the placebo, then the next day the would repeat the cough survey to quantify the difference in cough between the two nights. So as they came to their paediatrician, wanting them to fix their child’s cough, they were asked if they wanted to participate in the study. If they consented, they immediately had to fill out a questionnaire about the child’s cough from the night before (when they didn’t have any treatment for their cough). All three randomised controlled trials used the same questionnaire which had five questions, each with 7 possible tick box answers. The questions were:
- How severe was your child’s cough last night?
- How frequent was your child’s cough last night?
- How bothersome was your child’s cough last night?
- How much did your child’s cough affect the child’s ability to sleep?
- How much did the child’s cough affect the parent’s ability to sleep?
The possible answers were:
- not at all
- not much
- a little
- a lot
- very much
Only parents who gave a score of at least 3, (“somewhat”) for at least 2 of these 5 questions, were then able to be included in the study. They managed to recruit 130 kids, but only 105 completed the study for whatever reason. They were then randomised into three groups: The first group got an artificially honey-flavoured dextromethorphan preparation. The second group got honey. And the third group got nothing. The honey they used was buckwheat honey. Good on them for making an artificial honey flavoured dextromethorphan! So the no treatment arm were not blinded but the honey and dextromethorphan groups were. And the investigators were blinded from all three interventions. They gave the honey or dextromethorphan in an unlabelled syringe and were told to give it to their child 30 minutes before bed that night. They then called them the next day and asked them to answer the exact same cough questionnaire that they did the day before.
The average age of the child was 5, the oldest person in the study was 17 and they were sick for an average of 4.5 days before presenting to the clinic. The primary outcome they were assessing, was the difference in cough frequency from the night they didn’t take anything to the next night when they had either the honey, dextromethorphan or nothing. The other outcomes were the other 4 questions in the survey: cough severity, cough bothersome-ness, child’s sleep and parental sleep. They determined that a clinically meaningful change in score would be 1. So dropping from “very much” to “somewhat” or from “somewhat” to “a little”.
A the start of the study, the average cough score for each of the 5 questions in the survey, was about 4 out of 6 which means, on average, they were ticking the “a lot” box. So my child’s cough effected my sleep “a lot” last night. How severe was your child’s cough last night? “a lot”. And so on and so forth.
So what did they find?
Well for all five of the outcomes, the greatest reduction in score was seen with honey, then dextromethorphan, then doing nothing. Important to note that the doing nothing group did improve, because as we know, these things just get better with time.
No need to go into the exact results of all five of these outcomes because they were all pretty much the same (and I don’t want to put you to sleep). But let’s look at the primary outcome: “cough frequency” as an example. “how frequent was your child’s cough last night?”. The night before, when they didn’t get any treatment, the average score for this question was 4 representing “a lot”. Giving them no treatment on the night of the experiment took their score down by 0.92. So it took the average response to this question down from “a lot” to “somewhat” just by doing nothing. Giving honey took the score down by 1.89 points, so from “a lot” to “a little”. While dextromethorphan took it down to somewhere in between, 1.39 points – so somewhere in between “somewhat” and “a little”. And that was the pattern for all their outcomes. Doing nothing leads to some improvements, giving honey lead to greater improvements and giving dextromethorphan disguised as honey was somewhere in between the two. But despite the fact that this pattern was easily visible for all five questions, only one of them reached statistical significance when camparing honey to doing nothing, and that was for cough frequency. The difference in score was 0.97…so just shy of that minimally clinically important difference of 1.
So that’s the first study. Yes some benefits, but questionable whether these benefits were meaningful. And this study was funded by the National Honey Board!
RCT 2 – (Shadkam, 2010)
This one was done in Iran in 2010 and was published in the Journal of Alternative and Complementary medicine. Here, they were comparing honey versus dextromethorphan versus diphenhydramine versus usual care.
They recruited 141 children, between the ages of 2-5 and randomised them into 4 groups. The first group got 2.5mL of honey. The second group got 2.5mL of dextromethorphan syrup, the third group for 2.5mL of diphenhydramine and the fourth group got usual care.
This was again, an overnight study – On the day they came into the paediatric clinic, they were given that same cough survey, then that night they had the intervention, and this time they came back into the clinic the next day where they did the questionnaire again.
Importantly, the methods used in this study were really poor. There was no blinding, which, granted is difficult to do with honey, but at least in the other study, they made an effort with honey flavoured dextromethorphan preparation. And while blinding patients is important, what’s even more important is blinding the researchers. There was no blinding of the researchers. There was no allocation concealment which always makes you wonder whether there was actually any randomization. But perhaps the weirdest part of this study was, and I quote: “Any ambiguous question for the mother, if any, was answered by a paediatrician” …what the? So the investigators were answering questions if the mothers didn’t know the answer? This makes it even more alarming when you consider that the investigators were not blinded. So if they had a personal belief that honey was better, they could very easily influence the results, even if only subconsciously.
The starting score for each of these questions was around 4 (which was the same as the other trial) and the results were pretty much identical to the other study. In the usual care group, the score went down to about an average of 2.5 across the outcomes from the questionnaire. In the honey group the score went down to about 1.5. And for dextromethorphan and the diphenhydramine, the score went down to 2. This time, when comparing honey to usual care, the improvement was statistically significant for all of the outcomes and they were all also clinically meaningful having at least a difference of 1 point between the two for each of the outcomes.
So that’s two down and what do we have so far: We have one study which showed a benefit for honey but only reaching statistical significance for 1 of 5 outcomes and questionable clinical significance and this second study which shows a statistical and clinically meaningful difference but at a high risk of bias. Let’s put all our eggs in the third study basket.
RCT 3 – (Cohen, 2012)
This one was done in Israel and compared eucalyptus honey, to citrus honey to labiatae honey to placebo. Which is awesome because as someone who does use honey in general practice, I always get asked, “which honey is best?”
This was the best designed out of the three trials. They recruited children between the ages of 1 and 5, from 6 paediatric clinics who were presenting with a nocturnal cough due to an URTI.
They used the exact same cough questionnaire as the other two studies. They managed to recruit 270 kids and blinded both the patient and their family as well as the investigators. They also concealed allocation.
They randomised them to 4 groups – 3 of them were honey but different types of honey (eucalyptus, citrus and labiatae honey) and the fourth group was placebo. For placebo, they used Silan date extract – which they report looks and tastes similar to honey. They were all packaged in little 10 gram packets and you couldn’t tell the difference between them.
Like the other two studies this study was only an overnight study – so they took the survey on the day of presentation, gave them the honey or placebo that night (30 minutes before bed), then redid the survey the next day – like the first study, an investigator called them and they did the second day questionnaire over the phone.
These kids were just over 2 on average and were sick for about 3 days when they presented. Again, they used the five separate questions of the cough survey as an individual outcome. The primary outcome was cough frequency and the other 4 were secondary outcomes.
So what did they find?
Well firstly, there was no difference between the 3 types of honey for any of the 5 outcomes.But, honey was superior to the placebo date syrup for all 5 of the outcomes. And this was statistically significant. The reductions were very similar to the other two trials.
On average, across the five outcomes, the date extract had a 1 point reduction in the cough score, while the 3 different honey’s had about a 2 point reduction in cough score.
Honey reduces the frequency and severity of cough in children associated with upper respiratory tract infections. It also improves child’s sleep and parental sleep. When compared head to head, it is superior to the vast majority of cough medications which either contain dextromethorphan or diphenhydramine as their active ingredient.
Cough medications have had a lot of serious adverse effects reported in the literature. Firstly, 15% of all childhood overdoses in America are from cough medications. One-third of the time it’s because the incorrect dose was given to the child by the parent, but in two-thirds of the time, it’s because the child found it, went “hmmmm…This tastes nice”….and drank the whole thing. But even with standard doses, dystopias have been reported, as has anaphylaxis, hallucinations, mania. But it’s not only these studies which show they don’t work, a separate Cochrane review has also found no benefit with dextromethorphan.
Well now we have honey! Kids love it. minimal risk and more effective than the medications out there. But do not give honey to babies <1 years old because of the risk of botulism.