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 than the 500 billion CFU 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. 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. 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.⁷ 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.

1. 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.
2. 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.
3. 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.

1. 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.
2. 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.

Leonard Smith, M.D.
Dr. Leonard Smith is a prominent Board-Certified, general, gastrointestinal and vascular surgeon who had a successful private practice for 25 years. In addition to his active surgery practice, he also incorporated lifestyle, diet, supplementation, exercise, detoxification, and stress management into many of the therapies he would prescribe. Many of his patients with cancer, cardiovascular disease, and other serious illnesses did so well under his treatment regimes that he began to devote most of his career to foundational health care and preventive medicine.

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abdominal, antibiotic associated diarrhea, Bifidobacteria, Bifidobacterium lactis, billion, bloating, bowel function, Clostridium difficile, colonic transit, colonize, Conditions, Diarrhea, digestive, dose, fecal, flatulence, functional bowel disorders, gastrointestinal, gut, Gut flora, high-dose probiotics, IBS, inflammatory bowel diseases, Irritable Bowel Syndrome, lactobacilli, Lactobacillus, Lactobacillus acidophilus, microbiota, multistrain, Probiotic, ulcerative colitis

Autism is a developmental disorder characterized by severe abnormalities in communication, social awareness and skills, and behavior. Before the 1980s, autism occurred in 2 to 5 of every 10,000 children. Today about 1 in every 110 children gets autism. This rapid increase cannot only be attributed to improved diagnosis, and also indicates there is more to the disorder than simply genetics. Indeed, autism is a combination of genetic predisposition with environmental factors that triggers its development.

One aspect of contributing factors, at least in a subset of children, involves gut dysfunction. Many reports describe gastrointestinal symptoms and abnormalities in up to 84% of children with autism.[1] From constipation, diarrhea, abdominal discomfort, food sensitivities and abnormal gut flora to immune dysfunction and gut and systemic inflammation, the digestive system plays a central role in many cases of autism.

One gut abnormality—lactose intolerance—found in people with autism was recently reported in the journal Autism. Intestinal disaccharidase activity was measured in 199 individuals with autism. Disaccharidase is an enzyme that breaks larger sugars (disaccharides) like lactose, maltose and sucrose into smaller sugars like glucose. Deficiency of lactase enzyme, the enzyme that breaks milk sugar, or lactose, into galactose and fructose, was found in 58 percent of autistic children and 65 percent of autistic adults. In children, boys under 5-years-old had 1.7-fold lower lactase activity than girls of the same age, indicating the problem may be more severe in boys. The study concluded that lactase deficiency is common in autistic children and may contribute to abdominal discomfort, pain and the observed abnormal behavior seen in autism. Further, the study points out that most autistic children with lactose intolerance are not identified when doctors take a clinical history.

A decrease in activity of a variety of carbohydrate-digesting enzymes has been reported in children with autism.[2] Carbohydrase and disaccharidase enzyme deficiency results in the incomplete breakdown of carbohydrates in the small intestine. These partially undigested carbs move into the colon where they are greeted by a large supply of “hungry” bacteria—including potentially pathogenic bacteria. This may explain the increased presence of Candida and Clostridia species found in the guts of autistics.[3][4]

Carbohydrate-digesting enzymes are not the only digestive enzymes that may cause problems in autism. Fat malabsorption is seen in some autistic children, resulting in fatty, loose, floating, foul-smelling stools, also known as steatorrhea. Further, a particular enzyme known as dipeptidyl peptidase-4 (DPP4) may be deficient in those with autism. This enzyme breaks a specific peptide bond in gluten and casein proteins. In fact, it is thought that a deficiency in this enzyme is responsible for the incomplete breakdown of casein and gluten peptides (known as gluteomorphins and casomorphins) that act as opioids in the central nervous system and are thought to contribute to autistic symptoms. Following a gluten-free and casein-free diet has been found helpful in many autistics because it eliminates exposure to these peptides, often relieving symptoms. Supplemental DPP4 can be given in cases where accidental ingestion of gluten- or casein-containing foods is suspected, but it is not recommended as a replacement for the gluten-free, casein-free diet.

In all, we see a variety of enzyme deficiencies in autism and it would be wise to supplement with a digestive enzyme formula that includes a variety of enzymes. Further, due to the many digestive abnormalities seen in autism, the HOPE Formula (High-fiber, Omega oils, Probiotics and digestive Enzymes) is a wise daily maintenance program to support gut health.

[2] Horvath K, et al., “Gastrointestinal abnormalities in children with autistic disorder.” J Pediatr 1999;135:559-63.

[3] Finegold SM, et al., “Gastrointestinal microflora studies in late-onset autism.” Clin Infect Dis. 2002 Sep 1;35(Suppl 1):S6-S16.

[4] Shaw W, et al., “Assessment of antifungal drug therapy in autism by measurement of suspected microbial metabolites in urine with gas chromatography—mass spectrometry. The Clinical Practice of Alternative Medicine Magazine. 2000;1:15-26.

Leonard Smith, M.D.

Dr. Leonard Smith is a prominent Board-Certified, general, gastrointestinal and vascular surgeon who had a successful private practice for 25 years. In addition to his active surgery practice, he also incorporated lifestyle, diet, supplementation, exercise, detoxification, and stress management into many of the therapies he would prescribe. Many of his patients with cancer, cardiovascular disease, and other serious illnesses did so well under his treatment regimes that he began to devote most of his career to foundational health care and preventive medicine.

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abdominal discomfort, Autism, bacteria, Candida, casein, casomorphins, Children, Clostridia, Constipation, Diarrhea, Digestive Enzymes, environmental factors, Enzymes, fat malabsorption, food sensitivities, gastrointestinal, gluten, gluteomorphins, gut, gut dysfunction, Gut flora, high-fiber, immune dysfunction, inflammation, lactose intolerance, Omega oils, pain, Probiotics, small intestine, symptoms

Notable News – You know how I’m always saying that everything comes back to your gut? Turns out scientists at Rush University Medical Center in Chicago are thinking the same thing!

In an upcoming study funded by the U.S. Department of Defense (as in, the big guys), researchers are going to look into whether the bacteria in our gut are linked to certain diseases—specifically the rise of breast cancer in women. Interestingly, they think that the gut bacteria passed from mother to child may be a risk factor for the development of breast cancer. And ladies, if that’s not a reason to show your digestive tract a little more TLC, I don’t know what is!

The exciting thing is that this is just one of many studies in the works to help us better understand how the bacterial environment in our intestines—and even the bacteria on our skin—affects our overall health. I don’t know about you, but I can’t wait to see what scientists find out, especially since I’ve been touting the benefits of better digestion for years.

Alright, maybe I sound a little overly excited about these studies, but think about it—those of us in the natural health world have known for decades that our gut bacteria are at the base of total-body health, and now the rest of the world is finally catching up!

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breast cancer, digestive system, gut bacteria, Gut flora, gut health, Rush University Medical Center

Notable News

Clostridium difficile (C. diff) – More than Difficult!  Chances are you’ve probably heard of C. diff before, or at least its most common (and least pleasant) side effect – the gut-wrenching diarrhea. I know, I know, here I go talking about poop again, but this is important! C. diff infections are becoming more common every year. Studies tell us that 7,000 people are infected each day, and 300 of those die from the infection. So I say the more we know about C. diff, the better.

Okay, let’s start with the basics – just what is C. diff anyway? It’s short for Clostridium difficile, a disease-causing bacterium that most often appears after a person has taken antibiotics. This happens because the good bacteria that are normally present in the intestines (and which help keep our immunity strong) are also destroyed by antibiotics. Basically, when we take antibiotics to fight infection, they kill a lot of the good bacteria in our gut along with the bad, which disrupts our normally healthy intestinal balance. And C. diff is one of those opportunistic little buggers that will quickly take over and multiply if it has the chance, causing a potentially dangerous infection whose symptoms include severe diarrhea, abdominal cramping and nausea.

Interestingly, another culprit in the C. diff epidemic has come to light. The use of proton pump inhibitors (PPIs) has been associated with a risk for C. diff infection.  PPIs are used to treat gastroesophageal reflux disease (GERD), also known as acid reflux. These drugs suppress the secretion of acid in the stomach. 

But Wait! We Need Our Stomach Acid!  One of the functions of stomach acid is to kill bacteria that comes in with food. When there is not enough stomach acid, as occurs in people taking PPIs, harmful bacteria like C. diff can enter the intestinal tract and quickly multiply.

Can You Say Superbug? Have you heard the term Superbug?  C. diff is a Superbug. Superbugs are bacteria that become resistant to antibiotic treatment, which means that after a while, taking antibiotics won’t do anything to stop the harmful effects of the bug. Antibiotic resistance is largely the result of over-prescribing antibiotics for every little sneeze or sniffle instead of giving the body a chance to fight off the infection on its own, and it’s become a huge concern in the medical community today. I’ll talk about this more in a later post, so stay tuned!

Bottom Line? Our intestinal flora – the friendly bacteria in our intestines – play a major role in our health. One particular probiotic called Saccharomyces boulardii has been found to be especially useful for people with C. diff, particularly those that have recurrent C. diff infections. The reason is because S. boulardii is actually a yeast organism, so it’s not destroyed by antibiotics like most bacteria, which means it can keep working in the body to protect against C. diff – even if you’re taking antibiotics. The bottom line is, maintaining a good balance of beneficial microorganisms (probiotics) in the gut is a vital part of creating digestive health, which as we all know is the foundation for total-body health!

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antibiotics, bacteriology, Clostridium difficile, dangerous infection, Diarrhea, diff infection, diff infections, digestive system, food, Gastroenterology, gastroesophageal reflux disease, GERD, Gut flora, Health_Medical_Pharma, microbiology, nausea, Probiotic, Saccharomyces boulardii