International Society of Sports Nutrition Position Stand: Probiotics

In the paper

“In competitive cyclists, West et al. [61] reported reduced severity of self-reported symptoms of lower respiratory illness and use of cold and flu medication over an 11-week winter training period with L. fermentum (PCC®) compared to placebo. Interestingly, this effect was only noted in males and not females.”

What the sources say

• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [61] West NP Pyne DB Cripps AW Hopkins WG Eskesen DC Jairath A Christophersen CT Conlon MA Fricker PA Lactobacillus fermentum (PCC(R)) supplementation and gastrointestinal and respiratory-tract illness symptoms: a randomised control trial in athletes Nutr J 2011 10 30 10.1186/1475-2891-10-30 21477383 PMC3083335 sourceExperimental — accuracy not yet measured

In the paper

“Obesity and a high fat/high calorie diet can alter gut bacteria and intestinal wall permeability, leading to the passage of LPS from within the gut lumen into the circulation (metabolic endotoxemia), where it initiates systemic inflammation [258].”

What the sources say

• Partly supported

  The Background states that obesity and fatty-food consumption are associated with reduced intestinal barrier integrity, allowing gut-derived endotoxin into circulation and contributing to low-grade inflammation. It does not say that obesity or diet alters gut bacteria, specifically address a high-calorie diet, or establish the full sequence as causal; the Conclusions describe the endotoxin-to-inflammation link as a possibility. Page numbers were not provided in our copy. (LLM, conf=0.86)

  cites [258] Tremellen K McPhee N Pearce K Metabolic endotoxaemia related inflammation is associated with hypogonadism in overweight men Basic Clin Androl 2017 27 5 10.1186/s12610-017-0049-8 28286655 PMC5341351 sourceExperimental — accuracy not yet measured

In the paper

“Endotoxin can reduce testosterone production by the testes, both by direct inhibition of Leydig cell steroidogenic pathways and indirectly by reducing pituitary luteinizing hormone drive and sperm production [259].”

What the sources say

• Partly supported

  The Discussion reports that endotoxin inhibits Leydig-cell steroidogenic pathways and that animal studies found reduced LH pulses and pituitary drive. It also says neither study in men found evidence of reduced LH drive. The paper does not establish reduced sperm production as an indirect mechanism of reduced testosterone production. (LLM, conf=0.86)

  cites [259] Tremellen K McPhee N Pearce K Benson S Schedlowski M Engler H Endotoxin-initiated inflammation reduces testosterone production in men of reproductive age Am J Physiol Endocrinol Metab 2018 314 E206 E213 10.1152/ajpendo.00279.2017 29183872 PMC5899218 sourceExperimental — accuracy not yet measured

In the paper

“These authors concluded that the gut microbiota acts as an endocrine organ, secreting neurotransmitters such as serotonin and dopamine, thereby controlling the hypothalamic-pituitary axis in athletes.”

What the sources say

• Partly supported

  The Abstract describes the microbiota as acting like an endocrine organ, with serotonin and dopamine as examples, but says it *may* control the HPA axis in athletes. The main-text section on hormone release says its role in exercise-induced stress adaptation remains unknown. The citing sentence overstates this tentative conclusion as established control. (LLM, conf=0.88)

  cites [280] Clark A Mach N Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes J Int Soc Sports Nutr 2016 13 43 10.1186/s12970-016-0155-6 27924137 PMC5121944 sourceExperimental — accuracy not yet measured

In the paper

“Of the 24 studies that assessed some metric of athletic performance, 17 reported a null effect, while 7 reported significant improvement.”

In the paper

“While there are some encouraging results, a large majority of studies have found no effect on aerobic performance.”

In the paper

“Of the 22 studies reviewed in this Position Stand that assessed the effect of probiotics on outcomes related to the immune system, 14 reported significant improvement, whereas 8 reported no effects.”

In the paper

“This latter group included significantly decreased concentrations of zonulin [63] and endotoxin [77], as well as intestinal hyperpermeability [132] and duration of GI-symptom episode.”

• Also stated in: § Benefits of probiotic supplementation in athletes · plain

  “Positive results reported included decreases in concentrations of zonulin and endotoxin, intestinal hyperpermeability and duration of GI-symptom episodes.”

What the sources say

• Not checked yetcites [63] Lamprecht M Bogner S Schippinger G Steinbauer K Fankhauser F Hallstroem S Schuetz B Greilberger JF Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial J Int Soc Sports Nutr 2012 9 45 10.1186/1550-2783-9-45 22992437 PMC3465223 source
• Not checked yetcites [77] Roberts Justin Suckling Craig Peedle Georgia Murphy Joseph Dawkins Tony Roberts Michael An Exploratory Investigation of Endotoxin Levels in Novice Long Distance Triathletes, and the Effects of a Multi-Strain Probiotic/Prebiotic, Antioxidant Intervention Nutrients 2016 8 11 733 10.3390/nu8110733 PMC5133117 27869661 source
• Not checked yetcites [132] Brennan, C.J.; Axelrod, C.; Paul, D.; Hull, M.; Kirwan, J.P. Effects of a novel probiotic on exercise-induced gut permeability and microbiota in endurance athletes (abstract). In proceedings of American College of Sports Medicine, Minneapolis, MN.

In the paper

“In this position stand, which reviews studies focused on probiotic supplementation in athletes and physically active individuals, 11 studies measured AEs and general supplementation tolerance, while 30 studies did not.”

In the paper

“Overall, probiotics have an excellent safety profile with a large majority of clinical trials involving probiotics not giving rise to major safety concerns [213].”

What the sources say

• Not checked yetcites [213] Sanders ME Akkermans LM Haller D Hammerman C Heimbach J Hormannsperger G Huys G Levy DD Lutgendorff F Mack D Safety assessment of probiotics for human use Gut Microbes 2010 1 164 185 10.4161/gmic.1.3.12127 21327023 PMC3023597 source

In the paper

“The current body of research has investigated a wide variety of species/strains, duration of use, and dosages with several different intended purposes (Table 4).”

In the paper

“| Lactobacillus (n = 35) | 1 × 109 – 10 × 1010 CFU |”

• Also stated in: § Regulation · plain

  “| Bifidobacterium (n = 18) | 7 × 107–9.5 × 109 CFU |”

• Also stated in: § Regulation · plain

  “| Streptococcus (n = 8) | 5 × 109–4.5 × 1010 CFU |”

In the paper

“In our review, we report a wide range of doses (Table 4), and in several studies the dosage was not reported.”

In the paper

“Similar to the type of probiotic used, the duration of supplementation has also been variable in the studies reviewed (Table 3). The shortest duration lasted 7 days [75, 76] and the longest lasted 150 days [68].”

What the sources say

• Not checked yetcites [75] Gill SK Teixeira AM Rosado F Cox M Costa RJ High-dose probiotic supplementation containing Lactobacillus casei for 7 days does not enhance salivary antimicrobial protein responses to exertional heat stress compared with placebo Int J Sport Nutr Exerc Metab 2016 26 150 160 10.1123/ijsnem.2015-0171 26479711 source
• Not checked yetcites [76] Gill SK Allerton DM Ansley-Robson P Hemmings K Cox M Costa RJ Does short-term high dose probiotic supplementation containing Lactobacillus casei attenuate exertional-heat stress induced Endotoxaemia and Cytokinaemia? Int J Sport Nutr Exerc Metab 2016 26 268 275 10.1123/ijsnem.2015-0186 26568577 source
• Not checked yetcites [68] West NP Horn PL Pyne DB Gebski VJ Lahtinen SJ Fricker PA Cripps AW Probiotic supplementation for respiratory and gastrointestinal illness symptoms in healthy physically active individuals Clin Nutr 2014 33 581 587 10.1016/j.clnu.2013.10.002 24268677 source

In the paper

“A PubMed search conducted in October 2019 yielded the following listings for various combinations of key terms: probiotic and athlete, n = 145; probiotic and rodent, n = 3407; probiotic and diabetes, n = 844; probiotic and child, n = 2930; probiotic and elderly, n = 2257.”

In the paper

“In addition, several studies used a combination of species and strains (n = 17), ranging from two up to 14 different species/strains.”

In the paper

“Despite the existence of shared, core mechanisms for probiotic function, health benefits of probiotics are strain- and dose-dependent.”

What the sources say

• Not checked yetcites [10] Pyne DB West NP Cox AJ Cripps AW Probiotics supplementation for athletes - clinical and physiological effects Eur J Sport Sci 2015 15 63 72 10.1080/17461391.2014.971879 25339255 source

In the paper

“Athletes have varying gut microbiota compositions that appear to reflect the activity level of the host in comparison to sedentary people, with the differences linked primarily to the volume of exercise and amount of protein consumption.”

What the sources say

• Not checked yetcites [15] Bressa C Bailen-Andrino M Perez-Santiago J Gonzalez-Soltero R Perez M Montalvo-Lominchar MG Mate-Munoz JL Dominguez R Moreno D Larrosa M Differences in gut microbiota profile between women with active lifestyle and sedentary women PLoS One 2017 12 e0171352 10.1371/journal.pone.0171352 28187199 PMC5302835 source
• Not checked yetcites [16] Clarke SF Murphy EF O'Sullivan O Lucey AJ Humphreys M Hogan A Hayes P O'Reilly M Jeffery IB Wood-Martin R Exercise and associated dietary extremes impact on gut microbial diversity Gut 1913 2014 63 10.1136/gutjnl-2013-306541 25021423 source
• Not checked yetcites [17] Petersen LM Bautista EJ Nguyen H Hanson BM Chen L Lek SH Sodergren E Weinstock GM Community characteristics of the gut microbiomes of competitive cyclists Microbiome 2017 5 98 10.1186/s40168-017-0320-4 28797298 PMC5553673 source

In the paper

“In thirty-three trained athletes, 12 weeks of winter training supplementation with a multi-species probiotic did not benefit athletic performance; however, the training load (hours per week) was higher in those who supplemented with the probiotic blend vs. the placebo group [78].”

What the sources say

• Not checked yetcites [78] Strasser Barbara Geiger Daniela Schauer Markus Gostner Johanna Gatterer Hannes Burtscher Martin Fuchs Dietmar Probiotic Supplements Beneficially Affect Tryptophan–Kynurenine Metabolism and Reduce the Incidence of Upper Respiratory Tract Infections in Trained Athletes: A Randomized, Double-Blinded, Placebo-Controlled Trial Nutrients 2016 8 11 752 10.3390/nu8110752 PMC5133134 27886064 source

In the paper

“Diet is an established modulator of gut microbiota composition, with significant change reported within 24 h of a dietary modification [32].”

What the sources say

• Not checked yetcites [32] David LA Maurice CF Carmody RN Gootenberg DB Button JE Wolfe BE Ling AV Devlin AS Varma Y Fischbach MA Diet rapidly and reproducibly alters the human gut microbiome Nature 2014 505 559 563 10.1038/nature12820 24336217 PMC3957428 source

In the paper

“Probiotics supplementation as an ergogenic aid for performance enhancement requires further investigation and may be indirect via modulation of other systems.”

In the paper

“However positive results were reported in thirty endurance athletes supplementing with a yogurt drink, either containing Streptococcus thermophilus or Lactobacillus delbrueckii ssp. bulgaricus or no probiotics over 30 days during intense aerobic training. There was a significant increase in VO2max and aerobic power in the Cooper aerobic test [45].”

What the sources say

• Not checked yetcites [45] Salehzadeh K The effects of probiotic yogurt drink on lipid profile, CRP, and record changes in aerobic athletes Life Sci 2015 9 32 37

In the paper

“Daily supplementation with probiotics reduced the incidence of URTI compared to placebo. In addition, supplementation limited exercise-induced reductions in tryptophan levels, which may reduce the risk of developing an infection.”

What the sources say

• Not checked yetcites [78] Strasser Barbara Geiger Daniela Schauer Markus Gostner Johanna Gatterer Hannes Burtscher Martin Fuchs Dietmar Probiotic Supplements Beneficially Affect Tryptophan–Kynurenine Metabolism and Reduce the Incidence of Upper Respiratory Tract Infections in Trained Athletes: A Randomized, Double-Blinded, Placebo-Controlled Trial Nutrients 2016 8 11 752 10.3390/nu8110752 PMC5133134 27886064 source

In the paper

“In a follow up study, 20 g of casein protein co-administered with B. coagulans GBI-30, 6086 (BC30) or a placebo in recreationally-trained individuals for 2 weeks increased recovery and decreased soreness after a muscle-damaging single-leg training bout [43].”

What the sources say

• Not checked yetcites [43] Jäger Ralf Shields Kevin A. Lowery Ryan P. De Souza Eduardo O. Partl Jeremy M. Hollmer Chase Purpura Martin Wilson Jacob M. ProbioticBacillus coagulansGBI-30, 6086 reduces exercise-induced muscle damage and increases recovery PeerJ 2016 4 e2276 10.7717/peerj.2276 27547577 PMC4963221 source

In the paper

“Probiotic supplementation with the post-workout recovery drink yielded greater reductions in body fat and increases in fat free mass after 10 weeks of resistance training than a placebo.”

What the sources say

• Not checked yetcites [103] Toohey JC, Townsend JR, Johnson SB, Toy AM, Vantrease WC, Bender D, Crimi CC, Stowers KL, Ruiz MD, VanDusseldorp TA, et al. Effects of probiotic (Bacillus subtilis) supplementation during offseason resistance training in female division I athletes. J Strength Cond Res. 2018. 10.1519/JSC.0000000000002675. 33105368 source

In the paper

“There were no group differences observed between those who took the probiotic and placebo for any measure of strength, performance, or body composition. However, those athletes who did supplement with probiotics had significantly lower serum TNF-α concentrations than the placebo group.”

What the sources say

• Not checked yetcites [83] Townsend Jeremy Bender David Vantrease William Sapp Philip Toy Ann Woods Clint Johnson Kent Effects of Probiotic (Bacillus subtilis DE111) Supplementation on Immune Function, Hormonal Status, and Physical Performance in Division I Baseball Players Sports 2018 6 3 70 10.3390/sports6030070 PMC6162611 30049931 source

In the paper

“For example, a 12-week study on 141 non-elite marathon runners during pollen season supplementing daily with L. rhammnosus GG (LGG) did not find a significant effect on allergic markers [54] or on the incidence of UTRI episodes [55].”

What the sources say

• Not checked yetcites [54] Moreira A Kekkonen R Korpela R Delgado L Haahtela T Allergy in marathon runners and effect of Lactobacillus GG supplementation on allergic inflammatory markers Respir Med 2007 101 1123 1131 10.1016/j.rmed.2006.11.015 17196811 source
• Not checked yetcites [55] Kekkonen RA Vasankari TJ Vuorimaa T Haahtela T Julkunen I Korpela R The effect of probiotics on respiratory infections and gastrointestinal symptoms during training in marathon runners Int J Sport Nutr Exerc Metab 2007 17 352 363 10.1123/ijsnem.17.4.352 17962710 source

In the paper

“Supplementation with the double-strain probiotic resulted in a 19% decrease of URTI risk, although this was not statistically significant.”

What the sources say

• Not checked yetcites [68] West NP Horn PL Pyne DB Gebski VJ Lahtinen SJ Fricker PA Cripps AW Probiotic supplementation for respiratory and gastrointestinal illness symptoms in healthy physically active individuals Clin Nutr 2014 33 581 587 10.1016/j.clnu.2013.10.002 24268677 source

In the paper

“One month of daily L. acidophilus supplementation significantly increased secretion of interferon (IFN)-γ from T cells in fatigued athletes to levels found in healthy athletes and increased the concentration of IFN-γ in saliva of healthy control athletes.”

What the sources say

• Not checked yetcites [53] Clancy RL Gleeson M Cox A Callister R Dorrington M D'Este C Pang G Pyne D Fricker P Henriksson A Reversal in fatigued athletes of a defect in interferon gamma secretion after administration of Lactobacillus acidophilus Br J Sports Med 2006 40 351 354 10.1136/bjsm.2005.024364 16556792 PMC2577537 source

In the paper

“Similarly, Gleeson et al. [60] examined the effects of Lactobacillus casei Shirota during 4 months of winter training in endurance-based recreational athletes and observed a significant reduction in URTIs compared to placebo. In addition, salivary IgA concentration was significantly higher in those consuming the probiotic.”

What the sources say

• Not checked yetcites [60] Gleeson M Bishop NC Oliveira M Tauler P Daily probiotic's (Lactobacillus casei Shirota) reduction of infection incidence in athletes Int J Sport Nutr Exerc Metab 2011 21 55 64 10.1123/ijsnem.21.1.55 21411836 source

In the paper

“Supplementation with the probiotic significantly reduced the length of URTI episodes and lowered the number of symptoms per episode compared to placebo. Moreover, there was a significant increase of CD4+/CD8+ (T helper/T suppressor) cells ratio in the probiotic group.”

What the sources say

• Not checked yetcites [79] Michalickova D Minic R Dikic N Andjelkovic M Kostic-Vucicevic M Stojmenovic T Nikolic I Djordjevic B Lactobacillus helveticus Lafti L10 supplementation reduces respiratory infection duration in a cohort of elite athletes: a randomized, double-blind, placebo-controlled trial Appl Physiol Nutr Metab 2016 41 782 789 10.1139/apnm-2015-0541 27363733 source

In the paper

“Shared, core mechanisms for probiotic function are evident, although some mechanisms may be more narrowly distributed, including those related to immunomodulation [121].”

What the sources say

• Not checked yetcites [121] Sanders M Merenstein D Merrifield C Hutkins R Probiotics for Human Use Nutr Bull 2019 43 212 225 10.1111/nbu.12334 source

In the paper

“The probiotic group had lower incidence of infection-related symptoms compared to placebo, although there was no difference in the severity of the symptoms between the two treatment groups.”

What the sources say

• Not checked yetcites [69] Haywood BA Black KE Baker D McGarvey J Healey P Brown RC Probiotic supplementation reduces the duration and incidence of infections but not severity in elite rugby union players J Sci Med Sport 2014 17 356 360 10.1016/j.jsams.2013.08.004 24045086 source

In the paper

“Probiotic supplementation significantly reduced URTI incidence and severity compared to placebo.”

What the sources say

• Not checked yetcites [57] Cox AJ Pyne DB Saunders PU Fricker PA Oral administration of the probiotic Lactobacillus fermentum VRI-003 and mucosal immunity in endurance athletes Br J Sports Med 2010 44 222 226 10.1136/bjsm.2007.044628 18272539 source

In the paper

“The probiotic supplementation prevented reduced NK cell activity after strenuous exercise which may enhance resistance against infections.”

What the sources say

• Not checked yetcites [67] Sashihara T Nagata M Mori T Ikegami S Gotoh M Okubo K Uchida M Itoh H Effects of Lactobacillus gasseri OLL2809 and alpha-lactalbumin on university-student athletes: a randomized, double-blind, placebo-controlled clinical trial Appl Physiol Nutr Metab 2013 38 1228 1235 10.1139/apnm-2012-0490 24195623 source

In the paper

“The GI tract and particularly the gut are quite adaptable and can be targeted to improve the delivery of nutrients during exercise while at the same time alleviating some (or all) of the symptoms [131].”

What the sources say

• Not checked yetcites [131] Jeukendrup AE Training the gut for athletes Sports Med 2017 47 101 110 10.1007/s40279-017-0690-6 28332114 PMC5371619 source

In the paper

“Further, the overall result is not conclusive as four studies reported positive results.”

In the paper

“Athletes may compromise their immune status with high training loads (over-reaching, over-training) which can increase the risk of illness such as URTIs.”

• Also stated in: § Mechanism of action · boosted

  “Numerous studies have shown that prolonged intense physical exercise is associated with a transient depression of immune function in athletes.”

What the sources say

• Not checked yetcites [116] Schwellnus M Soligard T Alonso JM Bahr R Clarsen B Dijkstra HP Gabbett TJ Gleeson M Hagglund M Hutchinson MR How much is too much? (part 2) International Olympic Committee consensus statement on load in sport and risk of illness Br J Sports Med 2016 50 1043 1052 10.1136/bjsports-2016-096572 27535991 PMC5013087 source
• Not checked yetcites [199] Gleeson M Bishop NC URI in athletes: are mucosal immunity and cytokine responses key risk factors? Exerc Sport Sci Rev 2013 41 148 153 10.1097/JES.0b013e3182956ead 23792489 source
• Not checked yetcites [200] Walsh NP Recommendations to maintain immune health in athletes Eur J Sport Sci 2018 18 820 831 10.1080/17461391.2018.1449895 29637836 source

In the paper

“GI problems often occur in endurance athletes and particularly during prolonged events such as cycling, triathlons and marathons [41, 127].”

What the sources say

• Not checked yetcites [41] de Oliveira EP Burini RC Jeukendrup A Gastrointestinal complaints during exercise: prevalence, etiology, and nutritional recommendations Sports Med 2014 44 Suppl 1 S79 S85 10.1007/s40279-014-0153-2 24791919 PMC4008808 source
• Not checked yetcites [127] Rehrer NJ van Kemenade M Meester W Brouns F Saris WH Gastrointestinal complaints in relation to dietary intake in triathletes Int J Sport Nutr 1992 2 48 59 10.1123/ijsn.2.1.48 1338583 source

In the paper

“Lamprecht et al. [63] suggested that the supplemented probiotics may activate the TLR2 signaling pathway resulting in improved intestinal barrier function, thus reducing an athlete’s susceptibility to endotoxemia and associated cytokine production [137].”

What the sources say

• Not checked yetcites [63] Lamprecht M Bogner S Schippinger G Steinbauer K Fankhauser F Hallstroem S Schuetz B Greilberger JF Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial J Int Soc Sports Nutr 2012 9 45 10.1186/1550-2783-9-45 22992437 PMC3465223 source
• Not checked yetcites [137] Jeukendrup AE Vet-Joop K Sturk A Stegen JH Senden J Saris WH Wagenmakers AJ Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men Clin Sci (Lond) 2000 98 47 55 10.1042/cs0980047 10600658 source

In the paper

“The physical up-and down movement of the gut during running could also explain an increase in the frequency of gut symptoms [41].”

What the sources say

• Not checked yetcites [41] de Oliveira EP Burini RC Jeukendrup A Gastrointestinal complaints during exercise: prevalence, etiology, and nutritional recommendations Sports Med 2014 44 Suppl 1 S79 S85 10.1007/s40279-014-0153-2 24791919 PMC4008808 source

In the paper

“Many of the studies reporting AEs (rarely serious AEs) either do not utilize the appropriate biological sampling and identification techniques or AEs are poorly reported.”

In the paper

“well-studied probiotic species include Bifidobacterium (ssp. adolescentis, animalis, bifidum, breve, and longum) and Lactobacillus (ssp. acidophilus, casei, fermentum, gasseri, johnsonii, reuteri, paracasei, plantarum, rhamnosus, and salivarius) [211].”

What the sources say

• Not checked yetcites [211] de Simone Claudio The Unregulated Probiotic Market Clinical Gastroenterology and Hepatology 2019 17 5 809 817 10.1016/j.cgh.2018.01.018 29378309 source

In the paper

“Consumption of some probiotic strains may improve intestinal barrier function by modulating tight junction permeability.”

In the paper

“Marteau [214] outlined four classes of possible side effects of probiotic use: systemic infections, detrimental metabolic effects, cytokine-mediated immunologic adverse events in susceptible individuals, and transfer of antibiotic resistance genes.”

What the sources say

• Not checked yetcites [214] Marteau P Safety aspects of probiotic products Naringsforskning 2001 45 22 24 10.3402/fnr.v45i0.1785 source

In the paper

“Moreover the benefits of probiotics are not validated by EFSA, jeopardizing the use of the term probiotic without an approved claim with some exceptions such as in Italy, Czech Republic, and Bulgaria [211].”

What the sources say

• Not checked yetcites [211] de Simone Claudio The Unregulated Probiotic Market Clinical Gastroenterology and Hepatology 2019 17 5 809 817 10.1016/j.cgh.2018.01.018 29378309 source

In the paper

“However, each strain is unique with respect to how it responds to and affects the host.”

In the paper

“The QPS list concerns consumption by the general healthy population and does not take into consideration potential risks for vulnerable populations and this is clearly mentioned.”

In the paper

“The general consensus is that probiotic ingestion is safe [221, 222], with large doses well tolerated and failing to exhibit any toxicity [223].”

What the sources say

• Not checked yetcites [221] Boyle RJ Robins-Browne RM Tang ML Probiotic use in clinical practice: what are the risks? Am J Clin Nutr 2006 83 1256 1264 10.1093/ajcn/83.6.1256 16762934 source
• Not checked yetcites [222] Tapiovaara L Lehtoranta L Poussa T Makivuokko H Korpela R Pitkaranta A Absence of adverse events in healthy individuals using probiotics--analysis of six randomised studies by one study group Benefic Microbes 2016 7 161 169 10.3920/BM2015.0096 26689224 source
• Not checked yetcites [223] Larsen CN Nielsen S Kaestel P Brockmann E Bennedsen M Christensen HR Eskesen DC Jacobsen BL Michaelsen KF Dose-response study of probiotic bacteria Bifidobacterium animalis subsp lactis BB-12 and Lactobacillus paracasei subsp paracasei CRL-341 in healthy young adults Eur J Clin Nutr 2006 60 1284 1293 10.1038/sj.ejcn.1602450 16721394 source

In the paper

“Probiotics can potentially modulate intestinal permeability and health of the cells of the gut lining improving nutrient absorption including minerals, peptides, and amino acids by decreasing inflammation and encouraging optimum development of the absorptive area of the villi.”

In the paper

“The U.S. Food and Drug Administration (FDA) classifies probiotics individually but has classified many as Generally Recognized As Safe (GRAS), safe for the use in foods and infant products [219].”

What the sources say

• Not checked yetcites [219] FDA. New Dietary Ingredients Notification Process. Washington; 2016.

In the paper

“Adhesion of probiotics to the intestinal mucosa may be a mechanism for modulation of the immune system.”

In the paper

“Probiotics also cause alterations in intestinal mucins that prevent pathogen binding.”

In the paper

“However, most probiotics in commercial use are derived from fermented foods with a long history of safe consumption, or from microbes that may colonize healthy humans [212].”

What the sources say

• Not checked yetcites [212] World Gastroenterology Organisation. Global Guidelines: Probiotics and Prebiotics. World Gastroentereology Oganisation. Milwaukee; 2017.

In the paper

“An international consensus statement in 2014 indicated that these are likely to provide general health benefits such as normalization of disturbed gut microbiota, regulation of intestinal transit, competitive exclusion of pathogens, and production of SCFAs [1].”

What the sources say

• Not checked yetcites [1] Hill C Guarner F Reid G Gibson GR Merenstein DJ Pot B Morelli L Canani RB Flint HJ Salminen S Expert consensus document. The international scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic Nat Rev Gastroenterol Hepatol 2014 11 506 514 10.1038/nrgastro.2014.66 24912386 source

In the paper

“AEs are often not well recorded in nutritional studies in general and probiotics are no exception to this.”

In the paper

“A systematic literature review of probiotic safety published in 2014 reported that “the overwhelming existing evidence suggests that probiotics are safe” for the general population, and that critically ill patients, postoperative and hospitalized patients and immunocompromised patients were the most at-risk groups wherein AEs occurred [220].”

What the sources say

• Not checked yetcites [220] Didari T Solki S Mozaffari S Nikfar S Abdollahi M A systematic review of the safety of probiotics Expert Opin Drug Saf 2014 13 227 239 10.1517/14740338.2014.872627 24405164 source

In the paper

“Caution is warranted for those with serious health conditions, such as severe acute pancreatitis, inflammatory bowel diseases, liver diseases, and HIV.”

In the paper

“There are dozens of bacterial strains that can be considered as probiotics, particularly those that produce lactic acid.”

In the paper

“Some of the most common commercially available strains belong to the Lactobacillus and Bifidobacterium genera.”

In the paper

“Probiotics have been used safely in foods and dairy products for over a hundred years.”

In the paper

“The mechanisms underlying the beneficial effects of probiotics in athletes are largely unknown but are likely to be multifactorial.”

In the paper

“However, the mechanisms by which probiotics enhance intestinal barrier function are not sufficiently studied.”

In the paper

“There are two aspects to safety: establishing the adverse effect profile of specific single-strain and multi-strain supplements (i.e., the safety of the strain(s) per se), and ensuring that marketed supplements meet stringent quality standards to ensure the correct strains are present and the product is free of contamination [217].”

What the sources say

• Not checked yetcites [217] Sanders ME Merenstein DJ Ouwehand AC Reid G Salminen S Cabana MD Paraskevakos G Leyer G Probiotic use in at-risk populations J Am Pharm Assoc (2003) 2016 56 680 686 10.1016/j.japh.2016.07.001 27836128 source

In the paper

“Further, probiotics have been studied in vulnerable groups, including infants, patients with severe acute pancreatitis, inflammatory bowel diseases, liver diseases, HIV, and other conditions [213, 216–218] with even greater cause for concern with the small number of products that contain high concentrations of up to 450–900 billion live bacteria per dose [211].”

What the sources say

• Not checked yetcites [213] Sanders ME Akkermans LM Haller D Hammerman C Heimbach J Hormannsperger G Huys G Levy DD Lutgendorff F Mack D Safety assessment of probiotics for human use Gut Microbes 2010 1 164 185 10.4161/gmic.1.3.12127 21327023 PMC3023597 source
• Not checked yetcites [216] Besselink MG van Santvoort HC Buskens E Boermeester MA van Goor H Timmerman HM Nieuwenhuijs VB Bollen TL van Ramshorst B Witteman BJ Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial Lancet 2008 371 651 659 10.1016/S0140-6736(08)60207-X 18279948 source
• Not checked yetcites [217] Sanders ME Merenstein DJ Ouwehand AC Reid G Salminen S Cabana MD Paraskevakos G Leyer G Probiotic use in at-risk populations J Am Pharm Assoc (2003) 2016 56 680 686 10.1016/j.japh.2016.07.001 27836128 source
• Not checked yetcites [218] Vallabhaneni S, Walker TA, Lockhart SR, Ng D, Chiller T, Melchreit R, Brandt ME, Smith RM. Centers for Disease Control and Prevention, see https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6406a6.htm.
• Not checked yetcites [211] de Simone Claudio The Unregulated Probiotic Market Clinical Gastroenterology and Hepatology 2019 17 5 809 817 10.1016/j.cgh.2018.01.018 29378309 source

In the paper

“Going beyond history of safe use, since 2007 the EFSA lists species presumed safe for human consumption under the “Qualified Presumption of Safety” (QPS) concept.”

In the paper

“Under Japanese regulations, probiotic products are in a distinct category of foods known as Foods for Specific Health Uses (FOSHU). For probiotic food products, efficacy claims are prohibited on the labeling.”

What the sources say

• Not checked yetcites [231] Amagase H Current marketplace for probiotics: a Japanese perspective Clin Infect Dis 2008 46 Suppl 2 S73 S75 10.1086/523338 18181727 source

In the paper

“Additionally, safety assessment of the probiotic strain should at a minimum determine: 1) patterns of antimicrobial drug resistance, 2) metabolic activities, 3) side effects noted in humans during clinical trials and after marketing, 4) toxin production and hemolytic potential if the probiotic strain is known to possess those properties, and 5) lack of infectivity in animal studies [226].”

What the sources say

• Not checked yetcites [226] Food and Agriculture Organization of the United Nations and World Health Organization Joint FAO/WHO working group report on drafting guidelines fro the evaluation of probiotics in food 2002

In the paper

“The FDA has recently agreed that in addition to weight, probiotic amounts can also be labelled in CFU.”

In the paper

“Labeling probiotic quantity by weight is not meaningful because this measure does not indicate the viability of the microorganisms in the product throughout shelf life. To the contrary, CFU are more representative of the quantity of viable microorganisms and gives consumers and healthcare professionals accurate information.”

In the paper

“In 2001, the FAO/WHO held the Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics, to develop standardized guidelines for evaluating probiotics in food that could lead to the substantiation of health claims [226].”

What the sources say

• Not checked yetcites [226] Food and Agriculture Organization of the United Nations and World Health Organization Joint FAO/WHO working group report on drafting guidelines fro the evaluation of probiotics in food 2002

In the paper

“In January 2017, the Council for Responsible Nutrition (CRN) and the International Probiotics Association (IPA) announced the development of scientifically-based best practices manufacturing guidelines for the labeling, storing, and stability testing of dietary supplements and functional foods containing probiotics [235].”

What the sources say

• Not checked yetcites [235] Giordano-Schaefer, J.; Ruthsatz, M.; Schneider, H. Overcoming distinctive regulatory barriers for the development of medical foods. Availabe online: https://www.raps.org/regulatory-focus%E2%84%A2/news-articles/2017/10/overcoming-distinctive-regulatory-barriers-for-the-development-of-medical-foods (Accessed on Oct 2017).

In the paper

“Health Canada uses a pre-market approval process for non-food like applications such as capsules, tablets, softgels and powders which requires companies to acquire a Natural Product Number (NPN) prior to bringing to market [3].”

What the sources say

• Not checked yetcites [3] de Vrese Michael Schrezenmeir J. Probiotics, Prebiotics, and Synbiotics Food Biotechnology 2008 Berlin, Heidelberg Springer Berlin Heidelberg 1 66

In the paper

“While rigorous scrutiny of product claims is apparent, there appears to be little regulation of the manufacturing process and almost no post-marketing regulatory follow-up [233].”

What the sources say

• Not checked yetcites [233] Kolacek S Hojsak I Berni Canani R Guarino A Indrio F Orel R Pot B Shamir R Szajewska H Vandenplas Y Commercial probiotic products: a call for improved quality control. A position paper by the ESPGHAN working Group for Probiotics and Prebiotics J Pediatr Gastroenterol Nutr 2017 65 117 124 10.1097/MPG.0000000000001603 28644359 source

In the paper

“The effects of probiotics are strain specific, and therefore, strain identity is important to link to a specific health effect as well as to enable accurate surveillance and epidemiological studies.”

In the paper

“From the examples provided, it is apparent that the current approach to regulation is inadequate and can lead to problems of quality, safety, and claim validity in commercial probiotic products used in a medical context, including those used in vulnerable populations [233].”

What the sources say

• Not checked yetcites [233] Kolacek S Hojsak I Berni Canani R Guarino A Indrio F Orel R Pot B Shamir R Szajewska H Vandenplas Y Commercial probiotic products: a call for improved quality control. A position paper by the ESPGHAN working Group for Probiotics and Prebiotics J Pediatr Gastroenterol Nutr 2017 65 117 124 10.1097/MPG.0000000000001603 28644359 source

In the paper

“Unfortunately, government regulatory organizations are highly varied across national borders and jurisdictions in regulation of probiotics, making uniform recommendations difficult.”

In the paper

“In two reviews related to dietary supplementation in athletes, dosing regimens were reported in the range between 1 × 109 to 4 × 1010 CFU [10, 40].”

What the sources say

• Not checked yetcites [10] Pyne DB West NP Cox AJ Cripps AW Probiotics supplementation for athletes - clinical and physiological effects Eur J Sport Sci 2015 15 63 72 10.1080/17461391.2014.971879 25339255 source
• Not checked yetcites [40] Rawson ES Miles MP Larson-Meyer DE Dietary supplements for health, adaptation, and recovery in athletes Int J Sport Nutr Exerc Metab 2018 28 188 199 10.1123/ijsnem.2017-0340 29345167 source

In the paper

“These guidelines were designed to facilitate transparency and consistency in the probiotic sector.”

In the paper

“Currently there is no clear set of recommendation or guidelines on probiotic use for athletes.”

In the paper

“The regulation of probiotics differs between countries as there is no universally agreed framework.”

In the paper

“With the interruption of probiotic intake, there is a reduction in the microorganism administered in the colon, and with 8 days of supplementation discontinuation, the probiotic is no longer detectable in the gut [236].”

• Also stated in: § Future directions · plain

  “Further, with the interruption of probiotic intake, there is a reduction in the microorganism administered in the colon, and with 8 days of supplementation discontinuation, the probiotic is no longer detectable in the gut [236].”

What the sources say

• Not checked yetcites [236] Kullen MJ Amann MM O'Shaughnessy MJ O'Sullivan DJ Busta FF Brady LJ Differentiation of ingested and endogenous bifidobacteria by DNA fingerprinting demonstrates the survival of an unmodified strain in the gastrointestinal tract of humans J Nutr 1997 127 89 94 10.1093/jn/127.1.89 9040550 source

In the paper

“In the European Union, probiotics and food supplements are regulated under the Food Products Directive and Regulation (regulation 178/2002/EC; directive 2000/13/EU). All health claims for probiotics have to be authorized by EFSA which has issued a list of microbial cultures that have a Qualified Presumption of Safety [232]”

What the sources say

• Not checked yetcites [232] European Food Standards Agency. Qualified Presumption of Safety. Available from: http://www.efsa.europa.eu/en/topics/topic/qualified-presumption-safety-qps. Access date: 10 Aug 2018.

In the paper

“A key element of the guidelines is labelling probiotic products in CFU, the scientifically accepted unit of measure for probiotics and used to report probiotic quantity in many studies conducted to assess the safety or benefits of probiotics.”

In the paper

“So far, EFSA has rejected all submitted health claims for probiotics.”

In the paper

“Further, dietary supplements are required to comply with Good Manufacturing Practice guidelines, but these do not extend to testing quality or efficacy [233].”

What the sources say

• Not checked yetcites [233] Kolacek S Hojsak I Berni Canani R Guarino A Indrio F Orel R Pot B Shamir R Szajewska H Vandenplas Y Commercial probiotic products: a call for improved quality control. A position paper by the ESPGHAN working Group for Probiotics and Prebiotics J Pediatr Gastroenterol Nutr 2017 65 117 124 10.1097/MPG.0000000000001603 28644359 source

In the paper

“Consistent with scientific literature, CFU are commonly used on probiotic product labels in many jurisdictions around the world to help consumers and healthcare professionals identify products providing probiotics in amounts shown to have benefit.”

In the paper

“Japan is viewed by many to be a global market leader given that probiotics are available as both foods and drugs [230], and was the first global jurisdiction to implement a regulatory system for functional foods and nutraceuticals in 1991.”

What the sources say

• Not checked yetcites [230] Arora M Baldi A Regulatory categories of probiotics across the globe: a review representing existing and recommended categorization Indian J Med Microbiol 2015 33 Suppl 2 10 10.4103/0255-0857.150868 25657150 source

In the paper

“In Brazil, probiotics are considered as functional foods, and considered to be different from food. But legislation asks for safety and efficacy demonstration of food products and hence all these products must be registered and approved by a health authority called National Health Surveillance Agency Brazil (ANVISA) [230].”

What the sources say

• Not checked yetcites [230] Arora M Baldi A Regulatory categories of probiotics across the globe: a review representing existing and recommended categorization Indian J Med Microbiol 2015 33 Suppl 2 10 10.4103/0255-0857.150868 25657150 source

In the paper

“Health Canada has provided a Natural Health Product monograph that includes dosage form(s), use(s) or purpose(s) recommended as well as minimum quantities”

In the paper

“Coqueiro et al. [188] noted that in clinical practice probiotic supplementation should be implemented for at least 14 days prior to competition or important events for the athlete.”

What the sources say

• Not checked yetcites [188] Coqueiro AY de Oliveira Garcia AB Rogero MM Tirapegui J Probiotic supplementation in sports and physical exercise: does it present any ergogenic effect? Nutr Health 2017 23 239 249 10.1177/0260106017721000 29214927 source

In the paper

“In Canada, probiotics have two modes of sale on the market, Natural and Non-Prescription Health Products Directorate (NNHPD) and Food Directorate [3, 228].”

What the sources say

• Not checked yetcites [3] de Vrese Michael Schrezenmeir J. Probiotics, Prebiotics, and Synbiotics Food Biotechnology 2008 Berlin, Heidelberg Springer Berlin Heidelberg 1 66
• Not checked yetcites [228] Zorzela L Ardestani SK McFarland LV Vohra S Is there a role for modified probiotics as beneficial microbes: a systematic review of the literature Benefic Microbes 2017 8 739 754 10.3920/BM2017.0032 28884589 source

In the paper

“Many probiotics are sold as dietary supplements, which do not require FDA approval before they are marketed. Dietary supplement labels are permitted to make claims about how the product affects the structure or function of the body without FDA approval, but they cannot make health claims (claims that the product reduces the risk of a disease) without the FDA’s approval [234].”

What the sources say

• Not checked yetcites [234] NIH. Probiotics: In Depth. https://nccih.nih.gov/health/probiotics/introduction.htm. 2016.

In the paper

“In a 2018 consensus statement, the International Olympic Committee noted moderate support for probiotic use in athletes with a daily dose of 1 × 1010 live bacteria [5].”

What the sources say

• Not checked yetcites [5] Maughan RJ Burke LM Dvorak J Larson-Meyer DE Peeling P Phillips SM Rawson ES Walsh NP Garthe I Geyer H IOC consensus statement: dietary supplements and the high-performance athlete Br J Sports Med 2018 52 439 455 10.1136/bjsports-2018-099027 29540367 PMC5867441 source

In the paper

“The TWK10 group had significantly higher endurance performance and glucose content in a maximal treadmill running test compared to the placebo group (P < 0.05), indicating that TWK10 supplementation may be beneficial to energy harvest.”

What the sources say

• Not checked yetcites [85] Huang WC Hsu YJ Li H Kan NW Chen YM Lin JS Hsu TK Tsai TY Chiu YS Huang CC Effect of Lactobacillus Plantarum TWK10 on improving endurance performance in humans Chin J Phys 2018 61 163 170 10.4077/CJP.2018.BAH587 29962176 source

In the paper

“These novel findings suggest a potential impact for microbe therapy in obese and/or aging athletes by imparting hormonal and gonadal features of reproductive fitness typical of much younger healthy individuals.”

In the paper

“Together, these studies suggest a role in which certain probiotics may enhance energy harvesting, and have health-promotion, performance-improvement, and anti-fatigue effects.”

In the paper

“Weight loss and physical activity seem to improve these symptoms [260].”

What the sources say

• Not checked yetcites [260] De Lorenzo Antonino Noce Annalisa Moriconi Eleonora Rampello Tiziana Marrone Giulia Di Daniele Nicola Rovella Valentina MOSH Syndrome (Male Obesity Secondary Hypogonadism): Clinical Assessment and Possible Therapeutic Approaches Nutrients 2018 10 4 474 10.3390/nu10040474 PMC5946259 29649106 source

In the paper

“Probiotic supplementation, both with and without resistance training, can decrease levels of body weight and fat mass in overweight and obese individuals, as well as female athletes [103, 241, 242].”

What the sources say

• Not checked yetcites [103] Toohey JC, Townsend JR, Johnson SB, Toy AM, Vantrease WC, Bender D, Crimi CC, Stowers KL, Ruiz MD, VanDusseldorp TA, et al. Effects of probiotic (Bacillus subtilis) supplementation during offseason resistance training in female division I athletes. J Strength Cond Res. 2018. 10.1519/JSC.0000000000002675. 33105368 source
• Not checked yetcites [241] Kim J Yun JM Kim MK Kwon O Cho B Lactobacillus gasseri BNR17 supplementation reduces the visceral fat accumulation and waist circumference in obese adults: a randomized, double-blind, Placebo-Controlled Trial J Med Food 2018 21 454 461 10.1089/jmf.2017.3937 29688793 source
• Not checked yetcites [242] Sanchez M Darimont C Drapeau V Emady-Azar S Lepage M Rezzonico E Ngom-Bru C Berger B Philippe L Ammon-Zuffrey C Effect of Lactobacillus rhamnosus CGMCC1.3724 supplementation on weight loss and maintenance in obese men and women Br J Nutr 2014 111 1507 1519 10.1017/S0007114513003875 24299712 source

In the paper

“The long-term effects of probiotic administration in athletes over several months or years on gut health, immune function and rates of illness are unclear, as in most studies the supplementation period was between 4 to 16 weeks.”

In the paper

“In mice who consumed a probiotic kefir daily over 4 weeks, swimming time-to-exhaustion was significantly longer, forelimb grip strength was higher and serum lactate, ammonia, blood urea nitrogen (BUN), and creatine kinase levels were lower after the swimming test [248].”

What the sources say

• Not checked yetcites [248] Hsu Yi-Ju Huang Wen-Ching Lin Jin-Seng Chen Yi-Ming Ho Shang-Tse Huang Chi-Chang Tung Yu-Tang Kefir Supplementation Modifies Gut Microbiota Composition, Reduces Physical Fatigue, and Improves Exercise Performance in Mice Nutrients 2018 10 7 862 10.3390/nu10070862 PMC6073576 29973525 source

In the paper

“Probiotic supplementation may have potential to remove and utilize blood lactate after exercise.”

In the paper

“Piqué et al. (2019) suggested the presence of key structures in the cell or supernatant fractions may confer probiotic properties, mainly through immune-modulation, protection against pathogens, and fortifying the mucosal barrier integrity [261].”

What the sources say