Professor Michael Gleeson led a team whose peer-reviewed study currently in press, ‘Daily Probiotic’s (Lactobacillus casei Shirota) Reduction of Infection Incidence in Athletes’, formed part of Yakult’s article 13.5 proprietary science dossier submission last summer.
This sought to gain EFSA (European Food Safety Authority) approval for the claim that a daily dose of Yakult’s Shirota strain maintained an upper respiratory tract defence against pathogens and maintained immune defences.
However, in its scientific opinion on the application, EFSA’s panel on dietic products, nutrition and allergies rejected the submission, ruling that no cause and effect relationship had been established between Yakult consumption and these health outcomes.
Gleeson’s Loughborough University study formed a key part of Yakult’s dossier submission – which included nine human intervention and three animal studies in all – and was a randomised, double-blind, placebo-controlled intervention with 84 endurance athletes as subjects.
Yakult a day keeps the common cold at bay?
Half the athletes consumed two bottles of fermented milk containing at least 6.5 x 109 of Lactobacillus casei Shirota (LcS) for 16 weeks during a winter training period, while the remaining subjects consumed a similar placebo drink.
The study’s primary outcome assessed incidence of upper respiratory tract infection (URTI), 66% for Yakult consumers against 90% in the placebo group, with symptoms noted including runny noses, sore throats, fevers, coughs, aches and pains.
The average number of cold episodes was also 50% lower in the group of probiotic drinkers, the study also found, with results indicating that this benefit was due to LcS maintaining levels of salivary immunoglobulin A, which helps prevent viral infections and can drop during periods of intense exercise.
Athletes drinking the probiotic drink also experienced significantly fewer days with gastrointestinal symptoms frequently suffered by triathletes and runners, while immune marker concentrations in biological samples were more positive.
Dispute over questionnaires used
However, study participants completed self-administered health questionnaires to indicate symptoms, rating them as ‘light’, ‘moderate’ or ‘severe’, an approach that EFSA’s panel disliked, noting that the survey was “constructed from previously validated questions to assess the incidence of URTI but no information on validation of the specific questionnaire used in the present study was provided”.
“The panel considers that it has not been shown that this approach provides an appropriate measure of the presence of URTI.”
The panel also noted, “A total of 26 subjects (31%) dropped out during the study, with data analysis performed in the population of completers only…the high dropout rate was not taken into account appropriately in the analysis of data for the entire duration of the study”
“The panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claim.”
However, Gleeson told NutraIngredients.com that criticism of the questionnaires was “nonsense, given that it’s the usual way to assess the presence of illness in clinical trials. Throat swabs are one possible method, but can’t cover all the pathogens that might have caused a given symptom”.
“EFSA also ignored the fact that, of subjects of sufferring from the common cold, around 75% were taking medication to treat it, and this seems a reasonable indication that they really were ill.”
Gleeson added: “Some people also call for medical practitioners to be present during such trials, but a doctor’s success rate in diagnosing URTI is only 60-70%, since all they will do is look down your throat, listen to your chest and ask ‘are you ill?’.”
Dropout rate explained
He also hit back at EFSA’s criticism at inadequate data analysis of the study’s ‘high dropout’ rate: “The number of dropouts was not unexpected, due to the athlete cohort meaning inevitable injuries, and also the fact that they can’t take liquids through airport security if they compete internationally.”
“But there were enough subjects – 58 completed the full 16 weeks – to conclude that the results are statistically significant as regards the reduction of symptoms with the Yakult treatment.”
So did Gleeson think that EFSA’s negative opinion had harmed the probiotic industry, given media coverage in its aftermath reporting that 'probiotics' per se don’t work?
“I can’t talk about effects on probiotic sales, and it’s important to note that most studies are strain specific so you can’t generalise about ‘probiotics’ when they show specific benefits. Others may not have beneficial physiological effects, so overall review literature sometimes reaches negative conclusions.
“The story is ongoing after EFSA’s opinion. But the company is due to publish its response imminently, as are the authors of the studies cited (myself included) and many independent experts, who I’m pleased to say oppose EFSA and support our viewpoint.”
A Yakult UK spokeswoman said: "I can confirm that in response to the EFSA opinion, Yakult has sent comments to the European Commission (EC). The EC has also received letters from various independent scientific experts. As yet we have received no response from EFSA."