gut and beyond: 21st century advances...separating fact from fiction: evidence-based answers to some...
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Gut And Beyond: 21st Century Advances in Nutrition
Dr. Robert G. Silverman DC, DACBN, MS, CNS, CCN, CSCS, CIISN, CKTP, CES, DCBCN, HKC, SASTM
If an egg is broken by an outside force, life ends
If an egg is broken by an inside force, then life begins
Great things happen from the inside
Separating Fact from Fiction:Evidence-based answers to some of the most difficult
Controversies and Conundrums in Gut Health
Objective
What’s the Problem?
THE THINKER, Auguste Rodin in 1902
Obesogenic Overview
• Obesity epidemic
• 50% of Canadian adults will be obese by 2030
• Obesity prevalence in adults in their 40’s and 50’s would be 60%
Additionally:
• 6 mil to 8.5 mil more people with diabetes
• 5.7 mil to 7.3 mil more cases of heart disease and stroke
• 490,000 to 670,000 additional cancers
• 26 to 55 mil quality–adjusted life years left
• Increase medical expenditures: 48 bil – 66 bil by 2030 (not including lost productivity estimated at 390 bil – 580 bil per year)
Wang YC, McPherson K, et al. The Lancet 2011. 378: p.815-25
Old Myths and New Realities about Weight Loss
• People are not prisoners of their genetics. Lifestyle changes can lead to long-term weight control
• Extreme weight-loss diets seldom effective for long-term weight control
• Increased exercise increases health, regardless of bodyweight or weight loss
• Obesity prevention is a life-long process
• Preventing obesity in children must involve parents
• Some drugs can promote weight loss but must be continued to maintain losses
K. Casazza, KR Fontaine, et al. New England Journal of Medicine 2013. 368:446-454
0
10
20
30
40
50
60
1971-1974 1976-1980 1988-1994 1999-2000 2000-2012
Protein
Obesity & Diabetes
Carbohydrates
Fat
% o
f C
alo
ric
Inta
ke
Change in Dietary Composition in Relation to Obesity Prevalence (1971-2010)
5
10
15
20
25
30
35
Pre
vale
nce
of
Ob
esit
y (%
)
Adapted from: Flegal KM, Int J Obes 1998; Hedley AA et al JAMA 2004;291(23):2847-50; Flegal KM et al, JAMA. 2012 307(5):491-7
1971-1974 1976-1980 1988-1994 1999-2000 2009-2010
Canadian Obesity Rate Inches Up to 27.7% in 2014
• Obesity rate up from 25.5% in 2013 and 23% in 2008
• Obesity rate increased most among Canadians aged 65+ since 2008
• More Canadians now classified as morbidly obese
• Canadians who are obese have lower well-being
http://www.gallup.com/poll/181271/0besity-rate-inches-2014.aspx. January 26, 2015
Surging Annual Worldwide Cost
of Obesity
Cost of managing obesity worldwide
has reached 2 trillion annually
McKinsey Global Institute
Obesity-Related Ills May Shave Up to 8 Years Off Your Life: Study
Excess weight also shortens the time you live free of chronic diseases that lower quality of life
Published online Dec. 5, The Lancet Diabetes & Endocrinology
No Nation Has Lowered Obesity Rate in 33 Years
• The Lancet, June 2014: Study combining 3 decades of data from 188 countries
• Nearly 30% of world’s population is overweight or obese –not one country has reduced its obesity rate in 33 years
New York Times, June 3, 2014
Obesity in Pregnancy Puts Child at Diabetes Risk
Conclusion: Study of more than 1.2 million children born in Sweden between 1992 and 2004 and monitored for several years, found a 33 percent higher risk for the disease among children whose mothers were obese during the first trimester of pregnancy, but were not diabetic themselves.
Obesity = Postural Compensation
Lipotoxicity: the result of unhealthy lifestyle choices
Lipotoxicity• ectopic fat accumulation in various
tissues and organs leading to pathologic changes and impaired function.
Ectopic• occurring in an abnormal position or
place; displaced.
What really determines health or disease for most of us?
Genetics
Physiology/
Biochemistry
Environment
Lifestyle
“Over 99% of us are born healthy and suffer premature death or disability only as a result of personal misbehavior and environmental conditions”. John Knowles 1977
Global Diabetes Rates Are Rising as Obesity Spreads• Global diabetes rate rose by nearly half over past two decades
• Prevalence of diabetes rising in rich countries for several decades –largely driven by increases in rate of obesity
• 45% rise in prevalence of diabetes worldwide from 1990 to 2013 –nearly all the rise in Type 2, which is usually related to obesity and is most common form of the disease
The Lancet, June 2015
Sugar, Fat and CVD
• Large meta-analysis of 72 studies on fat show no link with CVD except trans fats Ann Intern Med. 2014;160(6):398-406
• Large meta-analysis on sugar found significant link to CVD:• HR for CVD 1.3 lowest and 2.75 for highest sugar
consumption JAMA Intern Med. 2014;174(4);516-52
• Large meta-analysis found sugar CVD risk factor independent of weight gain American Journal Clinical Nutrition 2014 May 7
New Dietary Guidelines
• Consumers should drastically cut back on sugar
• Limit to 10% of daily calories
• Limits on cholesterol removed
• W.H.O. also almost suggested removing sugar
• Men and boys should consume less protein
FDA, 1.6.2015; NY Times, 1.7.16
Failure of Current Treatment Models
• Calorie restriction – Failure of Model
• Why it fails: Compensatory mechanisms defend against weight loss by decreasing energy expenditure and increasing appetite
• Calorie hypothesis: Flaws• Multiple factors regulate metabolism:
• Dietary composition, microbiome, toxins, infections, allergens, nutrient status, mitochondrial dysfunction, hormonal and neurotransmitters dysregulation, social
Are all calories equal?
1,300 calories
New Weight Loss Drug
A NEW DRUG
There are too many people counting calories and
not enough people counting chemicals
The primary driver of chronic disease is the interaction among genes, activities of daily
living (lifestyle), and the environment
Willett WC. Balancing lifestyle and genomics research for disease prevention. Science, 2002;296:695-97Thorpe KE, Florence CS, et al. The rising prevalence of treated disease: effects on private health insurance spending. Health Affairs, web exclusive, June 27, 2005Henry RP. Long-latency deficiency disease: insights from calcium and vitamin D. Am J Clin Nutr 2003;78:912-9
Why doesn’t the old healthcare model work?
Obesity Is Tied to Pollutants
• New study – exposure to secondhand smoke and roadway traffic may be tied to increased body mass index in children and adolescents
• Researchers studied 3,318 children in 12 Southern California communities beginning at average age of 10, and then followed them through age 18
• Compared with children exposed to no secondhand smoke or near-roadway air pollution, BMI was 0.80 higher in children exposed to pollution alone, 0.85 higher in those exposed to secondhand smoke alone, and 2.15 higher in those exposed to both
Enviromental Health Perspectives, 2012
“obesity and diabetes have joined the list of
adverse effects that have been associated with
developmental exposure to environmental
estrogens and other endocrine-disrupting
chemicals.”
Am J Clin Nutr. 2011 Dec;94(6 Suppl):1939S-1942S
Chemical exposure may be linked to rising rates in diabetes and obesity
• Particular concern to unborn children exposed to EDCs
• Studies demonstrated that exposure to even very small amounts of EDCs during pregnancy can trigger obesity in the child later in life
• EDCs directly target beta and alpha cells in the pancreas, fat cells, and liver cells, which can lead to insulin resistance and type-2 diabetes
Chemical exposure may be linked to rising rates in diabetesand obesity
• The Journal of Clinical Endocrinology and Metabolism, March 2015: EDC exposure will likely cost the EU $209 billion a year in actual health care expenses and lost earning potential
Is your belly turning you into a pregnant woman?
The Obesity Epidemic: It’s a Guy Thing
• The other gender gap
• 72% of men are overweight or obese; 64% for women
• Life expectancy is less for men
• CHD mortality starts at younger ages for men
• 3 main factors:• Declining testosterone
• Increasing visceral fat
• Chronic inflammation
An Estrogen Factory
• Overweight men 9x more likely to have low testosterone
• Insulin sensitivity has a strong inverse relationship with visceral fat (VF)
• VF is an estrogen factory
• VF converts testosterone to estrogen to further fat deposition
Testosterone
Insulin resistanceWeight gain
Visceral fat
Low Testosterone Linked to Obesity and Muscle Loss
Lower levels of testosterone and free testosterone linked to increased body fat, body mass index
(proportion of weight to height) and waist-to-hip ratio
Journal Clinical Endocrinology Metabolism. 98:p.2442-50, 2013
Additional Causes of Low T
• Estrogen and estrogen-like compounds in our water:• Government researchers found natural estrogens and estrogen mimickers in 80% of
the streams they tested in 30 states
• Excess estrogen in body: new consideration – beta-glucuronidase:• Protocol: Indole-3-carbinol, Probiotic
• High levels of aromatase enzymes (estrogen synthase):• Transforms androstenedione to estrone• Transforms testosterone to estradiol
• Takeaway: it converts steroid hormones to bad estrogens• Protocol: Indole-3-carbinol
Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, Environmental Science & Technology
Low “T”
• Links exposure to phthalates – to a 13% lower testosterone level in men ages 40-60
J of Clin Endocrinology & Metab, 2014 report
Declining Testosterone
• Current measure indicate that testosterone levels are declining at a rate greater than would have been expected purely from aging
Travison, T. et al. Clin Endocrinol Metab. 2007: 92(1) p.196-202
Low-T
• U.S. prescription testosterone sales – 2.4 in 2013
• Expected growth to 3.8 by 2018
• Happening without FDA approval
• Testosterone therapy approved for males who suffer from medical conditions associated with a deficient or absence of endogenous test
• U.S. prescriptions grew ten-fold from 2000 to 2011
Time Magazine, Aug. 18, 2014
Testosterone gel has modest benefits for men
NESM, Feb. 17, 2016
“Time the healer also time the destroyer”
Tips for Men: Nutritional Support for Low T
• CYCYP test – great motivation
• Detox/heavy metal/estrogen detox/avoid plastics
• Improve body composition/cut simple carbs
• Eat more monounsaturated fats – increase manufacture of testosterone
• Squat, don’t run – squats, pushups and burpees burn more fat than running
• Add vitamin D, zinc, omega-3 fatty acids, DHEA, Indole-3-carbinol, resveratrol
• Tribulus, cowage seed, flax lignans, ashwagandha root
The Endocrine Society, news release, June 25, 2012
Best Time of Day for a Testosterone Test
Before 2 PM
The Journal of Urology, July 2014
Case Study
• Patient is a 40 year-old male who is unable to lose weight. Has to take Viagra to “perform”. Has tried various diets, including Androgell
Jan. 2014 Aug. 2014
Weight 284 215
% Body Fat 33.1 15.8
Total Testosterone 176 622 QuestLab250-1100ng/dl
Free Testosterone 38 168 QuestLab46-224 pg/nl
HPQ 62 12
Anti Inflammatory drugs (NSAIDS) cause leaky gut.Leaky Gut causes inflammation
Inflammation
NSAIDS cause
Leaky Gut vs. Healthy GI Tract
“A high percentage of abnormal [IntesinalPermeability (leaky gut)] IPT values were found among patients with autism (36.7%) and their relatives (21.2%)compared with normal subjects (4.8%).”
J Pediatr Gastroenterol Nutr. 2010 Oct;51(4):418-24
GI inflammation and leaky gut initiate a cascade of signaling events that can increase inflammation
Scharz B, et al. Intestinal ischemic reperfusion syndrome: pathophysiology, clinical significance, therapy: Wien Klin Wochenschr 1999;111(14):539-48
Liver Stress/ Kupffer Cell Activation
Digestion & Barrier Integrity Problems
Localized Inflammation
Gut barrier dysfunction may lead to inflammation, toxicity and chronic conditions
How many are affected by Inflammatory Bowel Disease (IBD)?
Approximately 1.1 million Americans currently have Crohn’s disease or ulcerative colitis. As many as 40,000 new cases of IBD are diagnosed in Canada each year.13
Loftus EV, Jr., Shivashankar R, Tremaine WJ, Harmsen WS, Zinsmeiseter AR. Updated Incidence and Prevalence of Crohn’s Disease and Ulcerative Colitis in Olmsted County, Minnesota (1970-2011). ACG 2014 Annual Scientific Meeting. October 2014.
Inflammatory bowel disease (IBD)
Definition:
Chronic inflammation of all or part of your digestive tract including ulcerative colitis and Crohn’s disease
Ulcerative colitis:
Inflammatory bowel disease that causes long-lasting inflammation and ulcers in the innermost lining of your colon and rectum
Crohn’s disease:
Recurring episodes of inflammation of any part of the gastrointestinal tract, from the mouth to the anus. It most commonly affects the end of the small intestine (the ileum) where it joins the beginning of the colon
Mayoclinic.org , clevelandclinicmeded.com, ccfa.org
IBD is a Lifetime ConditionThere are Many Cycles of Remission and Relapse
Pariente et al. Inflamm Bowel Dis. Jun 2011; 17(6): 1415–1422
“Over 10 million Canadians experience some kind of digestive problem… total health
care costs exceed $15 billion annually.”
American College of Gastroenterology
We’re Perfectly Positioned
GI Tract: Food sensitivitiesLeaky gut syndromeYeast/FungusDysbiosis ( Good bacteria)
Body Composition: Obesity
Insulin: Blood sugar problemsPre-diabetes/DiabetesInsulin resistance
Liver: Liver dysfunctionToxins/Chemical overload
Musculoskeletal System:Arthritis/Joint painSoft-tissue injuryCytokine, MMPS
Brain: SatietyInflammatoryNeurodegeneration
Dr. Rob’s Gut Matrix
The average human has 100 trillion microbes in the gut. 10 times more
than the cells in the human body. The
Microbiome outnumbers “our”
genetics 150:1
Prakash S, et al. Gut microbiota: next fier in understanding human health
The Gut’s the Body’s
Second Brain
Probiotics: Exploring the Mutually Beneficial Effects of Bacteria and Their Substrates in the Human Host
PROBIOTICS
Regulate local and systemic immune
function Metabolic pathway
nutrients: glycemic control, cholesterol, amino acids
Support mucosal barrier (multiple mxs)
Enhance nutrient utilization
Prevent neoplastic changes
Regulate bowel mobility
Regulate appetite (leptin, ghrelin)
Regulate inflammation, local & systemic)
Prevent infections (systemic & GI)
Mechanisms of Protection
1) Enhancement of the epithelial barrier
2) Increased adhesion to intestinal mucosa
3) Inhibition of pathogen adhesion
4) Competitive exclusion of pathogenic microorganisms
5) Production of anti-microorganism substances
6) Modulation of the immune system
Bermudez-Brito et al. Ann Nutr Metab 2012
Critical Issues on Selection and Use of Probiotics
• Genome Sequenced
• Safety AssessmentStrain Characterization
• Strain viability, robustness of growth
• Shelf stability
• Ability to survive bile and gastric acids
• Ability to arrive at the site of action
Stability, Quality and Ability to Get to the Right Place
• A diverse microbiota is associated with a healthy diet and lifestyle, as well as improved health outcomes
• Single strain or multispecies probiotics can impact diversity
General Benefit: Diversity of Gut Microbiota
• How does it work?
• What are the metabolites?
• Is function dependent upon cell-to-cell interactions?
Specific Benefit: Understanding the metabolic processes and
target functions
• Clinically relevant mechanisms of action should be defined.
• For specific health benefits– clinical studies meeting FDA guidelines will be required.
Preclinical and Clinical Targets, effects and outcomes
Clinical Use of Probiotics
Where does the rubber meet the road?
Daily Immune Health & Digestive Support
Formula (per capsule)
• 15 billion live organisms
• A 50:50 blend of Lactobacillus acidophilus, NCFM® and Bifidobacterium lactis Bi-07
• Dairy and Gluten Free
• Dosage: One capsule daily
• For overall GI health:– Supports healthy digestive function
– Aids in lactose digestion
– Competitively inhibits pathogenic microbes
– Supports the health of the GI barrier
L. acidophilus NCFM is one of the most researched strains
• DNA has been fully mapped
• Safe—Commercially available since the 1970s
• Subject of over 60 publications
• Survives GI transit
L. acidophilus NCFM is one of the most well-researched probiotic strains
In vitro tests of importance to intestinal functionality
Acid ToleranceR ++++
Bile Salt ToleranceR +++
Pepsin ResistanceI +++
Pancreatin ResistanceI ++++
Adherence to Human Intestinal CellsN (HT-29 and/or Caco-2
cells: in vitro)
+++
L/D-lactate Production Molar RatioR 60/40
Pathogen Growth InhibitionN
Salmonella typhimurium +
Staphylococcus aureus +++++
Escherichia coli ++++
Listeria monocytogenes +++
Urogenital pathogens Ref. 18
Cholesterol Assimilation Refs. 19, 20
Bacteriocin Production Refs. 21,22,23
See Appendix A for methods and coding
Origin of Information N=North Carolina State University (USA) R= Rhodia (USA) I= Institut Pasteur de Lille (France)
NCFM: IL - 10 Induction
0
200
400
600
800
1000
Control 8826 NCFM®
pg/m
l Control
8826
NCFM®
NCFM: IF - γ Induction
0
20000
40000
60000
Control 8826 NCFM®
pg
/ml Control
8826
NCFM®
Cytokine Activity
Published Studies
Survivability
• DNA has been fully mapped and is under nutrigenomic study
• Numerous human studies:• GI colonization
• Improved lactose digestion
• Reduced markers of small bowel bacteria overgrowth
• Reduced incidence of infection in school-aged children
• Additional animal investigations:• Reduced pre-cancerous lesions (rats)
• Reduced activity of fecal enzymes correlated with carcinogenic activity (rats and humans)
• Protected against Candida infection (mice)
Patient benefits:
•Relief from recurring abdominal discomfort, bloating, cramping, bowel irritation, and urgent bowel movements
•Clinical shown to reduce bowel complaint frequency and improve quality of life
Targeted Relief for Recurring Intestinal Distress
Formula (Serving size: 1 Capsule)
•A 50:50 blend of:
Lactobacillus acidophilus NCFM® and
Bifidobacterium lactis Bi-0760 billion live organisms
•Dairy and Gluten Free
High dose of probiotics (L. acidophilus NCFM and B. lactis BI-07) have been studied clinically in numerous models
• Improved quality of life
• Significant symptomatic improvement
The probiotics (L. acidophilus NCFM and B. lactis BI-07) have been studied clinically in numerous models of bowel distress
The similar efficacy, in treating pain, of orally administered L. acidophilus NCFM and a standard dosage of morphine suggests that specific modulation of intestinal flora may be a … treatment for abdominal pain, a prominent symptom of irritable bowel syndrome”
“These observations suggest that inoculation with probiotics can effectively prevent bacteria-induced colitis by limiting enteric bacteria infection and promoting mucosal protective regulatory immune responses.”
Pediatr Res. 2005 Dec;58(6):1185-91
Nat Med. 2007 Jan;13(1):35-7. Epub 2006 Dec 10
• Faber, S. The treatment of abnormal gut flora improves symptoms in IBSpatients using IBS-QOL. Amer. Coll of Gastroenterol 66th Ann Sci Mtg, May 28, 2001: Abstract #750369
• Faber, S. The Treatment of Abnormal Gut Flora Improves Symptoms In Patients with Irritable Bowel Syndrome, Abstract # 96, J Can Gastroenterol, Digestive Disease Week Alberta Canada. Feb. 2001
• Johnston, WM. Probiotics Relieve IBS Symptoms Linked to Abnormal Gut Flora. Gastroenterology and Endoscopy News, p.38, May 2001
• Faber, S. Irritable Bowel Syndrome and Reinoculation with Probiotics, Amer. Coll of Gastroenterol 67th Ann Sci Mtg, October 19, 2002 Abstract #336
• Scheduled for 2003: Faber, S. J Can Gastroenterol, Digestive Disease Week, Alberta Canada, February 2003
Multiple articles related to L. acidophilusNCFM and B. lactis BI-07 in IBS patients
Targeted probiotic support for nasal, sinus, and respiratory health
Formula (Serving size 1 capsule)
• 1 Billion 50:50 Blend** of Lactobacillus paracasei 8700:2, Lactobacillus plantarum HEAL9
• 30 Capsules per Bottle
• Dairy Free
• Gluten Free
• Vegetarian
Summary of clinical studies on a combination of L. plantarum HEAL9 and L. paracasei 8700:2
• Increase in immuno-supportive activity
• Reduced incidence and delayed onset of episodes of elevated upper respiratory symptom scores in healthy adults
• Significantly faster resolution of bothersome symptoms compared to placebo
• Significant reductions in the intensity of total symptoms and key individual symptoms
1. Berggren A, Lazou Ahrén I, Larsson N, Önning G. Randomised, double-blind and placebo-controlled study using new probiotic lactobacilli for strengthening the body immune defence against viral infections. Eur J Nutr. 2011;50(3):203-210
2. Busch R, Gruenwald J, Dudek S. Randomized, double blind and placebo controlled study using a combination of two probiotic lactobacilli to alleviate symptoms and frequency of common cold. FNS. 2013;4(11A):13-20
Mode of Delivery• 28% of births in the Canada are by Cesarean delivery
• Infants born by C-section:• Have lower gut flora diversity
• Have altered microbial profiles
• Are more likely to be colonized by pathogens
• MacDorman MF, Menacker F, Declercq E. Cesarean birth in the United States: epidemiology, trends, and outcomes. Clin Perinatol. 2008 Jun;35(2):293-307.• Matamoros S, Gras-Leguen C, Le Vacon F, et al. Development of intestinal microbiota in infants and its impact on health. Trends Microbiol. 2013;21:167-73.• Adlerberth I, Wold AE. Establishment of the gut microbiota in Western infants. Acta Paediatr. 2009;98:229-38.
Cesarean Section and Chronic Immune Disorders
Conclusion: Children delivered by cesarean delivery had significantly increased risk of asthma, systemic connective tissue disorders, juvenile
arthritis, inflammatory bowel disease, immune deficiencies, and leukemia
Sevelsted A, et al. Pediatrics 2015
Daily Probiotic Support for children in a chewable tablet
• Clinically demonstrated in children to support immune health
Formula (serving 2 chewable tablets)
• 10 billion live organisms per chewable tablet
• A 50:50 blend of Lactobacillus acidophilus, NCFM® and Bifidobacterium lactis Bi-07
• Dairy and Gluten free
• Serving size: chew 1-2 tablets per day
The probiotics (L. acidophilus NCFM and B. lactis BI-07)may also support healthy immune function
“CONCLUSIONS: Daily consumption of NCFM and Bi-07 and of NCFM alone significantly reduced the incidence and duration of respiratory tract infection symptomsin children.”
Pediatrics 2008;121;S115, Arthur Ouwehand, Greg Leyer and Didier Carcano
Targeted Relief for Acute Bowel Distress
• That have recently taken antibiotics
• Have plans to travel abroad
• Have concerns about supporting a healthy immune system
• One capsule per day:• 5.5 billion cfu S. boulardii - Combat pathogenic microbes, address
post antibiotic and travel associated GI distress
• 3 billion cfu B. lactis HN019 - stimulate immune cell production and natural killer cell activity
• 1 bullion cfu L. rhamnosus HN001 - stimulate immune cell production and natural killer cell activity
Supports the removal pathogenic microbes
S. boulardii is a great tool to help your patients combat harmful microbes
Pediatr Nephrol. 2006 Jun;21(6):807-10
Influence of oral intake of Saccharomyces boulardii on Escherichia coli in enteric flora
Ipek Akil1, 4 , Ozge Yilmaz1, Semra Kurutepe2, Kenan Degerli2 and Salih Kavukcu3Abstract Enteric flora constitutes 95% of the cells in the human body. It has been shown that the bacterial content of this flora is affected by diet and changes in nutrition. Considering that urinary tract infections (UTI) are mostly due to ascending infections from the gut flora, the importance of the elements of this flora and their characteristics becomes more evident. The aim of this study was to evaluate the influence of oral Saccharomyces boulardii (S. boulardii) intake on the number of Escherichia coli (E. coli) colonies in the colon. This study was carried out with 14 boys and 10 girls (total of 24 children) aged between 36 and 192 months (mean: 104.3±45.1 months). A commercial capsule or powder containing 5 billion colony-forming units (cfu) of S. boulardii was administered once a day for 5 days. The number of E. coli and yeast colonies was measured in the stool samples of the study group before and after the use of this drug. Before treatment, the mean number of E. coli colonies in g/ml stool was 384,625±445,744. This number decreased significantly to 6,283±20,283 after treatment (p=0.00). S. boulardii
was not detected in stool before treatment and the number of colonies increased to 11,047±26,754 in g/ml stool. S. boulardii may be effective in reducing the number of E. coli colonies in stool. The influence of this finding on clinical practice such as prevention of UTI needs to be clarified by further studies.
Am J Gastroenterol. 2006 Apr;101(4):812-22
Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the
treatment of Clostridium difficile disease.
Lynne V. McFarland, Ph.D.1,21CONTEXT: Antibiotic-associated diarrhea (AAD) is a common complication of most antibiotics and Clostridium difficile
disease (CDD), which also is incited by antibiotics, is a leading cause of nosocomial outbreaks of diarrhea and colitis. The
use of probiotics for these two related diseases remains controversial. OBJECTIVE: To compare the efficacy of probiotics
for the prevention of AAD and the treatment of CDD based on the published randomized, controlled clinical trials. DATA
SOURCES: PubMed, Medline, Google Scholar, NIH registry of clinical trials, metaRegister, and Cochrane Central Register of
Controlled Trials were searched from 1977 to 2005, unrestricted by language. Secondary searches of reference lists,
authors, reviews, commentaries, associated diseases, books, and meeting abstracts. STUDY SELECTION: Trials were
included in which specific probiotics given to either prevent or treat the diseases of interest. Trials were required to be
randomized, controlled, blinded efficacy trials in humans published in peer-reviewed journals. Trials that were excluded
were pre-clinical, safety, Phase 1 studies in volunteers, reviews, duplicate reports, trials of unspecified probiotics, trials of
prebiotics, not the disease being studied, or inconsistent outcome measures. Thirty-one of 180 screened studies (totally
3,164 subjects) met the inclusion and exclusion criteria. DATA EXTRACTION: One reviewer identified studies and abstracted
data on sample size, population characteristics, treatments, and outcomes.DATA SYNTHESIS: From 25 randomized
controlled trials (RCTs), probiotics significantly reduced the relative risk of AAD (RR = 0.43, 95% CI 0.31, 0.58, p < 0.001).
From six randomized trials, probiotics had significant efficacy for CDD (RR = 0.59, 95% CI 0.41, 0.85, p=
0.005).CONCLUSION: A variety of different types of probiotics show promise as effective therapies for these two diseases.
Using meta-analyses, three types of probiotics (Saccharomyces boulardii Lactobacillus rhamnosus GG, and probiotic
mixtures) significantly reduced the development of antibiotic-associated diarrhea. Only S. boulardii was effective for CDD.
J Infect Dis. 1993 Nov;168(5):1314-8.
Inhibition of Candida albicans translocation from the gastrointestinal tract of mice
by oral administration of Saccharomyces boulardii.
Berg R, Bernasconi P, Fowler D, Gautreaux M.
Dept. of Microbiology and Immunology, Louisiana State University Medical Center, Shreveport 71130.
Microbial translocation is defined as the passage of viable microbes from the gastrointestinal (GI) tract to extraintestinal
sites, such as the mesenteric lymph node (MLN), spleen, liver, kidneys, and blood. The ability of orally administered viable
Saccharomyces boulardii to inhibit Candida albicans translocation from the GI tract was tested in antibiotic-decontaminated,
specific pathogen-free (SPF) mice, which were orally challenged with C. albicans to promote intestinal overgrowth and
subsequent translocation of this organism. Oral S. boulardii treatment reduced the incidence of MLN cultures positive for C.
albicans but did not decrease the numbers of C. albicans per gram of MLN in these immunocompetent mice. Prednisolone
immunosuppression increased translocation of C. albicans to the MLN and allowed translocating C. albicans to spread
systemically to the spleen, liver, and kidneys. In these immunosuppressed mice, orally administered S. boulardii decreased
both the incidence of C. albicans translocation to the MLN, liver, and kidneys and the number of translocating C. albicans
per gram of MLN, spleen, and kidneys.
E. Coli
C. Difficile
Pakistan Journal of Biological Sciences 9 (4): 632-635, 2006
The Preventive Effect of Sacharomyces boulardii in Pathogenesis of Salmonella
typhimurium in Experimentally Infected Rats
M. Mahzounieh, I. Karimi, T. Zahraei Salehi and R. Marjanian
The present research studied the capacity of Saccharomyces boulardii (S. boulardii) to antagonize Salmonella typhimurium
(S. typhimurium) in the intestinal tract and humoral response of rats after challenging with S. typhimurium. Sixty
conventional male rats were divided at random into 4 groups. The S.boulardii suspensions contained 106, 07 and 108 cells
mL-1 were administered (orally) to 3 groups (A, B and C) of rats, respectively for 5 continues days. The rats of group D
received Saline instead of S.boulardii and used as control. All of rats challenged with 107 CFU of pathogenic S. typhimurium
at fifth day. The viable Salmonella were counted at g-1 of faeces of rates at 0, , 3, 5 and 7 days after challenge. Titer of anti-
salmonella antibodies were determined. Present experiments showed that S. boulardii could reduce the bacterial
colonization in experimental animals. There was a significant reduction at number of S. typhimurium between control and
test groups. A daily dose of 106 yeast cells was resulted in the most reduction in bacterial shedding and high titers of anti
salmonella antibodies. The mortality rates were 0 and 46.4% in yeast treatment and control animals, respectively. S.
typhimurium viable cells were not detected in the organs of yeast-treated rats. We conclude that S. boulardii has a
preventive effect in pathogenesis of S. typhimurium.
Candida albicans
Salmonella
During and after antibiotic therapyAm J Gastroenterol. 1995 Mar;90(3):439-48
Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo.McFarland LV, Surawicz CM, Greenberg RN, Elmer GW, Moyer KA, Melcher SA, Bowen KE, Cox JL.OBJECTIVES: To determine the safety and efficacy of a new preventive agent for antibiotic-associated diarrhea (AAD) in patients receiving at least one beta-lactam antibiotic. METHODS: A double-blinded, placebo-controlled, parallel group study was performed in a high-risk group of hospitalized patients receiving a new prescription for a beta-lactam antibiotic and having no acute diarrhea on enrollment. Lyophilized Saccharomyces boulardii or placebo (1 g/day) was given within 72 h of the start of the antibiotic(s) and continued until 3 days after the antibiotic was discontinued, after which the patients were followed for 7 wk. RESULTS: Of the 193 eligible patients, significantly fewer, 7/97 (7.2%), patients receiving S. boulardii developed AAD compared with 14/96 (14.6%) on placebo (p = 0.02). The efficacy of S. boulardii for the prevention of AAD was 51%. Using a multivariate model to adjust for two independent risk factors for AAD (age and days of cephalosporin use), the adjusted relative risk was significantly protective for S. boulardii (RR = 0.29, 95% CI = 0.08, 0.98). CONCLUSION: The prophylactic use of S. boulardii given with a beta-lactam antibiotic resulted in a significant reduction of AAD with no serious adverse reactions.
“CONCLUSION: The prophylactic use of S. boulardii…resulted in a significant reduction of AAD (antibiotic-associated diarrhea)”
Support the your patients’ GI health by prescribing S. boulardii when using antibiotics
Prescribe powerful B. lactis HN019 for demonstrated support for immune function
Am J Clin Nutr 2001;74:833–9. American Society for Clinical Nutrition
“Consumption of B. lactis HN019 led to average increases in cellular immune function of between 14.5% and 61.8%, with the greatest effect on NK cell activity”
“B. lactis HN019 may therefore offer the most promise as a dietary supplement for optimizing or restoring effective immunity”
“Of the immune responses that were enhanced by dietary consumption of HN001, phagocytic activity by PMN (polymorphonuclear) cells constitutes an important anti-microbial defense mechanism … while NK cell killing activity is thought to be important in the control of viral-infected cells.”
“It is therefore possible that enhanced performance by these cells, following consumption of HN001, could lead to an increased ability of consumers to fight infectious diseases”
J Am Coll Nutr. 2001 Apr;20(2 Suppl):149-56.
Revolutionary L. rhamnosus HN001 for additional immune support
Targeted Relief for Recurring Minor GI Pain
Patient benefits:
• Clinically demonstrated relief of recurring intestinal irritation, minor GI pain and bowel discomfort
Formula (Serving size: 2 Capsules)
• Lactobacillus plantarum 299v Strain
• 20 billion live organisms
• 60 capsules per bottle
• Vegetarian
• Dairy and Gluten Free
Clinical applications of 299v in treatment of minor GI pain and intestinal irritation
Administration of Lactobacillus plantarum 299v reduces side-effects
of external radiation on colon anastomotic healing in an experimental
model.
Liu Q, Nobaek S, Adawi D, Mao Y, Wang M, Molin G, Ekelund M, Jeppsson B.
OBJECTIVE: Preoperative radiotherapy of patients with rectal carcinoma is frequently used to reduce the incidence of local recurrence. However, the radiation therapy is associated with several complications, including diarrhea, retarded anastomotic healing and mucosal atrophy. Exogenous administration of lactobacilli has been demonstrated to be effective in stimulating intestinal mucosal growth and reduce mucosal inflammation. The objective of this study was to examine the effects of Lactobacillus plantarum 299v administration on external radiation injury in colon anastomotic healing at different time points. MATERIAL AND METHODS: Sprague-Dawley rats were treated with Lb. plantarum 299v or saline as control and received external radiation of the lower abdomen (10 Gy/day) on day 3 and 7 of the experiment. After 4 days, a colonic resection with anastomosis was performed. Animals were sacrificed on 4th, 7th and 11th day postoperatively. Body weight, white blood cell (WBC) count, mucosal myeloperoxidase (MPO) activity, hydroxyproline, nucleotide, DNA and RNA content, colonic bacterial microflora, bacterial translocation and histology were evaluated. RESULTS: On the 4th postoperative day body weight, WBC and MPO decreased significantly after radiation. On the 7th postoperative day MPO decreased after radiation. In the two irradiated groups it decreased significantly in the Lb. plantarum group compared to the radiated group without treatment. Collagen concentration on the 7th postoperative day was significantly higher in Lb. plantarum group without radiation compared to the group with radiation without Lb. plantarum. On the 11th postoperative day MPO was significantly higher in irradiated rats without treatment compared to Lb. plantarum treatment. The collagen concentration increased significantly in the irradiated Lb. plantarum group compared to the other two groups. CONCLUSION: The collagen content decreased and MPO activity increased significantly of the colonic anastomosis in irradiated rats without treatment compared to those treated with Lb. plantarum. It therefore seems that administration of Lactobacillus plantarum 299v reduces the intestinal injury and inflammation following external radiation and improves the colonic anastomotic healing.
Colorectal Dis. 2001 Jul;3(4):245-52
“administration of Lactobacillus plantarum 299v reduces the intestinal injury and inflammation… and improves the colonic anastomotic healing.”
A new tool to better manage GI inflammation in your patients
Conclusion:“…Lactobacillus plantarum can improve the results
of classical …therapy of ulcerative colitis.”
L. Plantarum 299V helps to balance inflammatory messages in the GI tract
• “fibrinogen concentrations decreased by 21% (P < 0.001) in the experimental group”
•“A highly significant 41% decrease in plasma IL-6 concentrations was observed”
L. plantarum 299V effects markers of systemic inflammation
Am J Clin Nutr 2002;76:1249–55
Patient benefits:• Helps maintain a healthy vaginal microflora by increasing the
number of beneficial Lactobacilli
• Supports urogenital health and comfort
• Backed by clinical trials that demonstrate support of healthy vaginal microflora
Formula (Serving size 1 capsule)• 2 Billion 50:50 Blend of Lactobacillus rhamnosus GR-1®,
Lactobacillus reuteri RC-14®• 30 Capsules per Bottle• Gluten Free• Vegetarian Capsule
Targeted Support for Feminine Health
Scientifically Shown to Support Feminine Health
Vujic G, Knez AJ, Stefanovic VD, Vrbanovic VK. Eur J Obstet Gynecol Reprod Biol. 2013 May;168(1):75-79
Efficacy of oral probiotics for vaginal health: a
double-blind, randomized, placebo-
controlled study
Information on the Two Probiotic StrainsL. rhamnosus GR-1• Isolated in 1980 from the distal urethra of
a healthy woman• Safety confirmed in numerous human and in
vitro studies• Able to colonize the vagina after oral intake• Produces bacteriocin-like compounds• Survives passage through the
gastrointestinal tract
Picture of Lactobacillus rhamnosus GR-1
L. reuteri RC-14• Isolated in 1985 from the vagina of a
healthy woman• Safety confirmed in numerous human and
in vitro studies• Able to colonize the vagina after oral intake• Produces hydrogen peroxide• Survives passage through the gastrointestinal
tract
Picture of Lactobacillus reuteri RC-14
Chris Hansen. Women's Flora. http://www.chr-hansen.com/products/product-areas/probiotics-for-dietary-supplements/health-areas/womens-flora.html. Accessed March, 2014
Supported by Clinical Data
• 5 randomized, controlled clinical trials on the effect of oral administration:
• 2 studies in healthy women• 3 studies in women with BV or yeast vaginitis
• 11 additional clinical studies:• 5 effect/colonization studies by vaginal application• 6 studies on colonization by oral administration
• ~175 scientific publications in total:• Human studies• Animal studies• In vitro studies• Reviews
Patient benefits:
• Provides support for both upper and lower GI tract
• Helps relieve recurring and acute functional bowel discomforts and intestinal irritation
• Proprietary probiotic blend of 7 beneficial microorganisms demonstrated to support digestion, intestinal health, and a healthy immune response
Formula (Serving size 1 capsule)• 30 Billion blend of:
• Lactobacillus acidophilus NCFM® • Bifidobacterium lactis Bi-07• Bifidobacterium lactis Bi-04 • Lactobacillus plantarum Lp-115• Lactobacillus salivarius Ls-33 • Streptococcus thermophilus St-21• Saccharomyces boulardii
• Dairy and Gluten Free
Broad-Spectrum Intestinal and Immune Health Support
Starting from day 1 we are
exposed to pro and prebiotics
10% of breast milk CHO is not digestable or absorbable in
proximal gut
What are they?Probiotics: live
microorganisms that confer a health benefit on the host
when administered in adequate amounts
Prebiotics: substrate for probiotics
Where found?Probiotics: in
fermented foods
Prebiotics: in many unprocessed foods
Probiotics + Prebiotics=
Synbiotics
Is it all about “Risk vs. Benefit”
Could probiotics or changing the “Microbiome” help with weight control?
Gut Bacteria ‘may be obesity weapon’
• Bacteria living in our gut affect our waistlines, harnessing them could lead to new ways of shedding pounds
• Study showed – transplanting gut bacteria from obese people into mice led to the animals gaining weight, while bacteria from lean people kept them slim
Published in Science
Diet Changes Gut Bacteria Within a DayHarvard study
• Changes in diets can quickly alter the types of bacteria that live in the human gut, often within a day
• Study suggests that rapid adaptability to different food may help control illnesses tied to stomach microbes
• Change in an animal-base diet showed really big shift in the number of microorganisms
• Increase was in anaerobic bacteria Bilophilia wadsworthia, which can cause colitis in lab mice
Nature, December 11, 2013
Gut Bacteria Diversity Improves with Exercise
• Study focused on a group of athletes
• Results: athletes had significantly wider range of gut microbiota than men in comparison groups
• Athletes also had better metabolic profiles than the men with a high BMI and much higher proportions of a type of bacteria that is known to be linked with lower rates of obesity and associated metabolic disorders
Medical News Today
Choosing Probiotic Supplement
• Should possess variety of live strains that translate into better protection from and prevention of illnesses that are caused by pathogenic bacteria
• Average of 10 Billion CFU
• Expiration date revealed
• GMP applied in the manufacturing process
Choosing Probiotic Supplement (cont’d)
• Supplement vehicle should be:• Digestive-resistant• Acid-resistant• Bile-resistant