Probiotic use for digestive conditions has seen a gradual increase in dosage over the past couple decades. Doses of 7 billion were thought to be very high just ten years ago, while average doses were about 250 million. Today, an average probiotic dose is around 1–5 billion with high-dose probiotics ranging from 30 to 450 billion or more. This increase comes with improvements in the development of probiotics and increased interest in studying high-dose probiotics, as is reflected in the literature.

The gut is home to about 100 trillion bacteria cells—10 times the amount of cells that make up the entire human body. For this reason, high-dose probiotic therapy may have a greater impact on the beneficial modulation of the gut flora, or microbiota. Here I’ll review a few studies on high-dose probiotics for gastrointestinal conditions.

In a randomized, double-blind, placebo-controlled study published in 2010 in the Journal of American Gastroenterology, 225 patients were randomized to one of three groups: two probiotic capsules per day providing 100 billion CFU (colony forming units) of live organisms, one probiotic capsule and one placebo capsule per day providing 50 billion CFU of live organisms, or two placebo capsules.¹ A dose-ranging effect was shown in which the group receiving the 100 billion CFUs had lower incidence of antibiotic-associated diarrhea (AAD) than the 50 billion group, and both probiotic groups had lower incidence versus placebo. In those patients who did acquire AAD, Clostridium difficile-associated diarrhea (CDAD) incidence was lower in the 100 billion CFU group than the 50 billion group, and both probiotic groups had lower CDAD incidence than placebo.

A previous dose-response study published in 1991 in the journal Microbial Ecology in Health and Disease investigated fecal recovery of the probiotic Lactobacillus casei strain GG (LGG).² In this study, healthy volunteers were assigned to six different groups: 1.5 million, 15 million, 150 million, 1.5 billion, 15 billion and 150 billion CFU per day of the probiotic. LGG could not be recovered from the feces of groups taking up to 150 million CFU per day. In the group taking 1.5 billion, LGG was occasionally recovered at low levels in two of the seven volunteers. In the group taking 15 billion CFU per day, all volunteers were colonized. LGG was recovered at the highest level with the highest dose—150 billion. This study showed a dose-response effect at higher dosage levels of 15 to 150 billion CFU per day required for fecal probiotic recovery.

A high-dose multistrain probiotic formula containing eight strains (three bifidobacteria, four lactobacilli and one Streptococcus) has also been shown to colonize the gut and maintain remission of ulcerative colitis (UC) in children and adults.^3-5 In children, 900 billion CFU per day of an eight-strain probiotic formula induced remission.³ In adults, 500 billion CFU per day of that same formula colonized the gut and maintained remission in UC patients.⁴ In another trial, a daily dose of 3.6 trillion CFU per day of the multistrain formula induced remission in adult patients not responding to conventional therapies.⁵

This same preparation (dosages ranging from 450 billion to 1.8 trillion CFU per day, based on weight of patient) was also found to induce and maintain remission of ulcerative colitis in children.⁶ In a randomized, double-blind, placebo-controlled trial of 29 children with UC, probiotics or placebo were added to standard treatment. In the probiotic group, 92.8 percent achieved remission compared to only 36.4 percent in the placebo group. Further, there were no biochemical or clinical adverse events related to the probiotic treatment in these children.

Two more randomized, controlled trials evaluated the effects of this probiotic preparation in twenty-five patients with diarrhea-predominant irritable bowel syndrome (IBS-D). In the first study, patients were assigned to receive either the probiotic mixture (450 billion CFU per day) or placebo for eight weeks.⁷ The multistrain probiotic relieved abdominal bloating when compared to placebo. In the second study, 48 IBS patients were randomized, double-blind, to receive either the probiotic mixture (450 billion CFU per day) or placebo for 4 or 8 weeks.⁸ The multistrain probiotic mixture reduced flatulence and slowed colonic transit without altering bowel function in patients with IBS and bloating.

In another double-blind, placebo-controlled trial, sixty patients with functional bowel disorders—non-constipation IBS, functional diarrhea and functional bloating—received a probiotic mixture of two strains, Lactobacillus acidophilus and Bifidobacterium lactis, at 200 billion CFU daily for eight weeks.⁹ Abdominal bloating improved in the probiotics group at four and eight weeks when compared to placebo. A subgroup of patients with IBS was analyzed and also found to have reduced bloating when compared to placebo.

Studies evaluating high-dose probiotics are most common for inflammatory bowel diseases, though as we see from the studies cited above, other conditions are also benefitted from a high-potency probiotic therapy. The trend toward increasing dosage of probiotics is influenced and supported by studies using doses ranging from 50 billion up to 3.6 trillion or more.

References

1. Gao XW, et al., “Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients.” Am J Gastroenterol. 2010 Jul;105(7):1636-41.
2. Saxelin M, et al., “Dose-response colonization of faeces after oral administration of Lactobacillus casei strain GG.” MicroEcol Health Dis. 1991 Jan;4:209-14.
3. Miele E, et al., “Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis.” Am J Gastroenterol. 2009 Feb;104(2):437-43.
4. Ringel Y, et al., “Probiotic bacteria Lactobacillus NCFM and Bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders—a double-blind study.” J Clin Gastroenterol. 2011 Jul;45(6):518-25.
5. Miele E, et al., “Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis.” Am J Gastroenterol. 2009 Feb;104(2):437-43.
6. Venturi A, et al., “Impact on the composition of the faecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis.” Aliment Pharmacol Ther. 1999 Aug;13(8):1103-8.
7. Bibiloni R, et al., “VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis.” Am J Gastroenterol. 2005 Jul;100(7):1539-46.
8. H.J. Kim, et al., “A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating.” Neurogastroenterol Motil. 2005 Oct;17(5):687-96.
9. H.J. Kim, et al., “A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome.” Aliment Pharmacol Ther. 2003 Apr 1;17(7):895-904.