Probiotics: does the hype exceed the evidence?


Despite the growing interest in probiotics, what does the evidence tell us and what advice should pharmacists be giving their customers? 

It seems that rising awareness of the link between diet and health, as well as of the important role played by our microbiome, is continuing to fuel the demand for probiotics.

According to research, the increasing trend towards the use of probiotics has been driven by the rise in digestive health issues in Australia’s ageing population.

Indeed, Complementary Medicines Australia’s annual audits show that probiotics was the fastest growing supplement ingredient in 2017–18 seeing a rise of 10.2%. While the period 2018–19 saw an 11.3% growth.

However, while there’s a lot of hype surrounding probiotics, it’s important to encourage customers who are interested in taking probiotics to focus on the evidence.

Probiotics are defined by the World Health Organisation as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. That sounds pretty good, but if only it were that easy!

Speaking to the AJP previously, Associate Professor Andrew Holmes from the University of Sydney explains there’s a lot of ambiguity around probiotics.

“The principal of probiotics is now well validated. Where there is a deficiency due to a specific microbe you could, in principal, add that microbe back in and achieve a benefit. However, this concept has been widely over‑interpreted.

“Health is multi-factorial; it is many things working together that deliver benefits. When things go wrong, they typically can’t readily be fixed by just adding one thing back in isolation. Probiotic therapy, as a principle, is sound. However, the principle also dictates that augmenting the microbiota with a probiotic will give the best results if it is filling a gap—but it also needs to be the ‘right gap’ that it is filling.”

In short, many of the arguments in support of probiotics are based on oversimplified concepts of what is really going on inside the body. While there is some evidence for the effectiveness of certain strains of bacteria, further research is needed. Additionally, unlike other pharmaceuticals, there is no set guideline on the dose required to gain a positive effect.

So, how can pharmacists best counsel people who are requesting probiotics or already convinced they are beneficial for all manner of ailments?

Surviving the stomach acid

Two of the most common probiotics are Lactobacilli and Bifidobacteria. These microbial organisms, which constitute a large part of the intestinal microflora in humans, can be found in yoghurt and fermented foods such as kimchi, Kombucha, miso and sauerkraut. However, many people choose to get their probiotics through supplements.

Complementary Medicines Australia 2020 Audit shows that pharmacy is the largest sales outlet for supplements, including probiotics. So, this places pharmacists at the forefront when it comes to offering information on the evidence and effectiveness of certain probiotic strains.

In a podcast professor Simon Gaisford from University College London’s school of pharmacy discusses probiotics with UK magazine Chemist + Druggist’s clinical editor Kristoffer Stewart.

Prof Gaisford explains, “Many consumers, as well as people in the medical profession, view probiotics with some scepticism. One of the problems with probiotics is that there’s a lot of misinformation.

“One of the reasons there’s so much misinformation about probiotics is that a lot of products are badly formulated. You can take them but I believe it’s unlikely they will deliver the number of viable bacteria needed to have an effect.

“It’s very difficult in vivo to determine exactly what’s going on inside the body. Everyone’s gut contains thousands of species of bacteria and yours will be different from mine.

“A lot of those species in the gut have never been identified or cultured in the laboratory. So we don’t really know what species are already there and how to measure the effect in vivo.”

There’s also the fact that probiotics need to survive in the acidic gastric environment in order to reach the small intestine and colonise the host, thus imparting their health benefits.

To address this, Prof Gaisford and his team performed their own test. They bought various OTC probiotics from a local pharmacy and added each product to a small volume of hydrochloric acid.

“We followed the manufacturer’s instructions in an attempt to recreate the process of a patient swallowing each product. So if it said to take the product with a glass of water, we added a glass of water into the beaker. If it was a liquid product, we added it straight in.

“We left the probiotics for 30 minutes, after which time the bacterial samples were removed from the acid and viable bacteria were counted. Results showed that for freeze-dried solid products, such as a sachet, capsule or tablet, there was very little bacterial activity. Therefore, a key finding is if a patient is going to buy a product, we should recommend buying a liquid-based probiotic rather than a solid product.

“This is simply because you’re asking the bacteria to rehydrate in a strong acid solution and our study showed that liquid products are better at providing a degree of protection against acid.”

Look at the bacteria

He adds that pharmacists can advise people to look at what bacteria are in the product. “Most contain a mixture of species, but typically they contain Lactobacillus and Bifidobacterium. It’s worth selecting a probiotic with as many bacteria as possible, as you might as well try to maximise your chance of getting viable bacteria.

“The other thing we recommend is to try to minimise the amount of time the product sits in your stomach acid. We usually recommend taking a probiotic first thing in the morning, before cleaning teeth or doing anything.”

Yet, despite these ongoing tests, there’s still no definitive data that links a specific strain of bacteria to a certain condition.

“Possibly one of the best reasons for taking a probiotic is if you have some sort of gut condition, such as bloating. This makes you feel uncomfortable and you want to try something to manage your symptom but not necessarily a medication, so people try probiotics,” says Prof Gaisford.

Of course, the problem with probiotic products is that they vary considerably not only in their form, but in the intended health claims, quality, dose and storage requirements.

The evidence for probiotics

Disruption to healthy gut microbiota (dysbiosis) has been associated with a number of health conditions including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS).

Furthermore, there is some evidence (albeit not particularly robust) to support the use of probiotics for certain conditions. Here’s a look at where the evidence currently lies, according to recent clinical guidelines.

IBS

There is some evidence to support the use of probiotics for IBS, but it is certainly not robust. National Institutes of Health (NIH) reports that while some strains of probiotics may be helpful in reducing some of the symptoms of IBS, further high-quality clinical trials are needed to confirm the specific strain.

It states that some strains of probiotics have shown modest positive benefits but no specific combination has been proven to be superior to another. Furthermore, treatment times vary from four weeks to six months.

However, the National Institute for Health and Care Excellence (NICE) recommends that if patients wish to try probiotics they should take them at a dose recommended by the manufacturer for a minimum of
four weeks.

The American Gastroenterological Association, on the other hand, makes no recommendations for the use of probiotics in children and adults with IBS, due to the knowledge gap.

Atopic eczema

The evidence to support the use of probiotics in pregnancy to reduce the risk of babies developing atopic dermatitis is scarce. The NIH says the effects of probiotics vary according to the strain used, the timing of administration, and the patient’s age, making it particularly difficult to offer a recommendation.

Most studies have been conducted with single strains or mixtures that include Lactobacillus, Bifidobacterium, and Propionibacterium.

One study of 6,907 infants and children exposed to probiotics in utero for 2 weeks to 7 months (via maternal oral supplementation) and/or by oral administration to the infants after birth for 2 to 13 months found the risk of atopic dermatitis dropped from 34.7% in the control group to 28.5% in the probiotic group.

In contrast, other studies have found that Lactobacillus rhamnosus GG (LGG) did not reduce the risk of eczema in children, regardless of the timing of administration.

However, clinical guidelines from the Royal Australian College of General Practitioners (RACGP) refer to medical trials in which mothers were given probiotic supplements from 34–36 weeks of gestation and continued postpartum until the baby was 3–6 months of age (or until weaned).

The probiotic species generally used is Lactobacillus rhamnosus GG and most often at a strength 2 x 10 colony forming units (CFU) daily. The guidelines state that effect seen across all probiotics tested was deemed to be moderate.

Antibiotic-associated diarrhoea

According to the RACGP guidelines, Lactobacillus rhamnosus GG and Saccharomyces boulardii appear to be the most efficacious choice for preventing antibiotic-associated diarrhoea. While Lactobacillus casei may be most appropriate for specifically preventing severe C. difficile-related diarrhoea.

During trials, probiotics were given at a dose of 10 to 50 billion CFUs daily. It’s recommended probiotics can be taken during and/or after antibiotic dosing.

The NIH states that, according to the evidence available, starting probiotic treatment with Lactobacillus rhamnosus GG or Saccharomyces boulardii within two days of the first antibiotic dose helps reduce the risk of antibiotic-associated diarrhoea in children and adults aged 18 to 64, but not in elderly adults.
It says there is no evidence to suggest that the benefits are greater when more than one probiotic strain is used. However, taking probiotics within two days of the first antibiotic dose is deemed more effective than starting to take them later.

Pharmacist’s advice

Lisa Barnes, pharmacy manager at Terry White Chemmart Coorparoo, QLD, says, “The market is flooded with probiotics and it can be a tough decision to choose the most appropriate product for the customer. However, it’s important that our pharmacists are confident in recommending products that have the evidence to support their use.

“As pharmacists, we are in the perfect position to educate our patients on the benefits of probiotics, particularly as they can potentially assist with common conditions that we see in the pharmacy every day. These include allergies, eczema and colic in babies, thrush, as well as preventing antibiotic-associated diarrhoea and supporting people who want to look after their immune system.

“Probiotics is quite a diverse area, with many different products and combinations of strains available. While there are no specific guidelines on dosage and there is still much research to be done in this area, it is important to explain to our customers that it is not always the product with the highest level of billion live bacteria (BLB) that will be the best for their individual situation.

“In fact, excessively large doses are not always supported by evidence and can actually cause side effects such as bloating and diarrhoea. The health benefits need to be considered based on specific strains and the clinical evidence available.

“Certainly, for patients wanting to treat a specific condition— for example thrush, allergies or eczema— are pregnant or breastfeeding, or are trying to achieve immune support, it is more important to select a product with the correct strains.”

Mrs Barnes explains that it’s essential for pharmacists to do their own research and align themselves with reputable companies who can provide documented clinical trial data on their products.

She says, “An innovative method being used by a particular company, Activated Probiotics, increases the rate at which probiotics survive the transit through the upper gastrointestinal tract without being destroyed by stomach acid. This is achieved by utilizing micro-encapsulation, a lipid layer protecting the live bacteria.

“Clinical trials have shown this can allow up to five times more bacteria to reach the large intestine, which is their intended site of action. These particular products include clinically proven strains of bacteria that target specific conditions. As such, our pharmacists feel confident to recommend these probiotics, due to the research behind them.

“People often tend to think the highest dose, broad-spectrum probiotic is always the best way to go. For me, the decision on which dosage form is best often comes down to the individual patient and what will fit in with their lifestyle. While there are many options available, the most appropriate product is what the patient will remember to take on a daily basis. If this means a capsule is the most suitable option, then this is what they should go with. For children or anyone with swallowing difficulties, a powder or liquid would be most appropriate.

“There is also the decision as to whether a refrigerated product is practical or convenient versus a shelf stable product.”

Having the conversation

Mrs Barnes says there are a growing number of conversations happening in her pharmacy about probiotics and their many benefits. She says this is partly thanks to consumer interest but also due to the fact probiotics have been a focus of in-store pharmacy training.

When considering the future of probiotics, Prof Gaisford explains, “The human microbiota is important and influences a vast array of things. Yet, while the probiotic field might not change much over the next 10 years our understanding of how the gut microbiota influences human health and wellbeing is going to grow enormously.

“The way I view a probiotic is that it’s providing a nutrient source that enables good bacteria to flourish irrespective of whatever else you consume or the disease state you have.

“In this sense, probiotic therapy allows your gut bacteria to recover to a position of natural equilibrium. I think that’s going to be a really critical step in alleviating the symptoms of some of the disease states we currently see and making patients feel a lot better, which may be followed up with medical treatment. I think that’s how the future will work.”

For the time being, pharmacists play a key role in staying up to date with the current evidence, working with reputable companies and fielding patient’s questions.

Prof Gaisford admits, “As a pharmacist, being asked what is good bacteria and what is bad is a difficult question to answer; it’s very open ended. Each individual strain of a bacterium can be good or bad depending on what it’s producing—and that level of knowledge is just not there yet.

“However, it’s fair to say a probiotic will probably confer some sort of benefit if you choose one that’s properly formulated and you take it in the right way!” 

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