Probiotic Supplements: Does Time of Day Matter?

After deciding which probiotic supplement offers the beneficial strains that meet your health goals, you may consider what time of day to take it. Is a probiotic supplement best taken on an empty stomach? Or perhaps it should be taken with food?

Various health sites and blogs offer advice on those very questions. Unfortunately, the inconsistent recommendations — some unsupported conjecture — can cause confusion among consumers:

Before breakfast

With a meal

Short time after a meal

Before bedtime

Let’s take a look at what is known, gathered from evidence-based sources.

Threats to probiotics in the stomach

Probiotics are live microorganisms which when targeting the small and large intestines must pass through harsh stomach acids.

Stomach acids aid in digestion of carbohydrates and proteins but also kill pathogens and viruses that may travel along with foods and beverages. They do have a purpose. Unfortunately, acids also kill beneficial microorganisms, depending on the type. Acidity is measured in pH values. The human digestive system has variable pH levels: The stomach has a pH of 1–3, whereas the small and large intestines have pH ranges from 6-7.

It is suggested then that probiotics should pass through the inhospitable environment as fast as possible. Taking a probiotic with food or a meal may slow that passage, killing more probiotics. But a meal can also increase the pH of the stomach, giving probiotics safer passage. On the other hand, a meal may also trigger digestive enzyme and bile salt production, affecting probiotic viability.

Thus, whether to take a probiotic supplement with a meal or on an empty stomach — thereby pinpointing a time of day — has been a subject of debate. Note that newer research uses simulated models of the GI tract rather than test tubes, which show better survival rates of probiotic bacteria than in test tubes.

One study?showed that survival of all the bacteria in the product was best when given with a meal or 30 minutes before a meal (cooked oatmeal with milk). Probiotics given 30 minutes after the meal did not survive in high numbers. In addition, survival improved when the supplement was taken alongside oatmeal or low-fat milk, compared with when it was taken with only water or apple juice. The authors concluded that “ideally, non-enteric coated bacterial probiotic products should be taken with or just prior to a meal containing some fats.”

Protective technology for probiotics

Fortunately, high quality probiotic manufacturers make gastric acid resistance and survivability a top priority.

Encapsulation is a proven method to protect probiotics to ensure their stability without any change in native strain properties. Various techniques have been explored for the encapsulation of probiotics to protect these live microorganisms and improve their stability and offer benefits in terms of targeted delivery. Confirmation of the delivery of probiotics can be done initially by in vitro studies using simulated static in vitro digestion or dynamic in vitro digestion system (simulator). Further study is needed to confirm in vivo efficacy. Use of enteric coated or delayed release capsules are additional approaches used by probiotic manufacturers to protect the delivery of probiotics against the acidic gastric environment.

Different strains survive better

Some bacterial strains are more resilient toward stomach acid and have better survival rates than others as they pass through the stomach. Survival rates of different strains can be improved depending on the delivery method of the probiotic supplement.

Gastric resistance varies from species to species and within strains.

Lactobacillus spp. (recently reclassified based on whole-genome sequencing) are more viable in gastric conditions compared to other probiotic species, thus making gastro-resistance less of a priority in choosing a dosage form for these probiotics.

A 2021 study?evaluated the survivability of five strains of lactic acid bacteria from commercial probiotics and under simulated conditions of the gastrointestinal tract. The strains were without protective capsules and added in a food matrix. Lactobacillus plantarum was the most resistant to the applied conditions of the culture medium. It showed a noticeable growth under both in vitro gastric conditions at pH 4.0 and 5.0, as well as in vitro intestinal conditions at all tested concentrations of bile salts.

The increased survival of probiotic lactic acid bacteria in acidic conditions in the presence of glucose has also been reported.

Interestingly, probiotics do not have an antagonistic effect on each other’s survival when used in a multi-strain product compared to a single-strain product, at least within a microbiota in a simulated colonic environment.

Other bacteria also show variation in acid survival within the same species:

The acid tolerance of bifidobacteria was found to be weak, with the exception of Bifidobacterium lactis and Bifidobacterium animalis.

In one study, Saccharomyces boulardii survived in equal numbers with or without a meal, suggesting that it may have some intrinsic protection.

Takeaway

A slim amount of evidence suggests that probiotics may survive better if given before a meal. Fortunately, time may be less germane since manufacturers have developed advanced techniques to protect probiotics through the harsh environment of the stomach. Even so, check the label instructions on your product to see if there are recommendations regarding how and when to take the probiotic as formulations vary greatly. Importantly

Above all, the strain chosen must always provide the evidence-based effective dose throughout the product shelf life to target your specific health need.

And finally, time may matter for one practical reason: Scheduling a time of day to take your probiotic supplement makes it easier to remember, ensuring consistent consumption so the full benefit can be realized.

NOTE: Probiotic supplements may also be delivered outside the GI tract

The issue of gastric conditions and bile exposure in the GI tract can be irrelevant when probiotic supplements are delivered to specific sites.

For example, positive results are seen when lactobacilli strains — dominant in the female urogenital tract — are delivered directly to the vagina.

The oral cavity has also been targeted for the prevention of conditions such as gingivitis and periodontitis.

In addition, rectally administered probiotic formulations show potential in treatments for inflammatory disorders such as ulcerative colitis.