RECOMMENDING SUPPLEMENTS: YES OR NO?

SATURDAY/11:00AM-12:00PM

ACPE UAN: 0107-9999-20-012-L01-P 0.1 CEU/1.0 hr

0107-9999-20-012-L01-T

Activity Type: Application-Based

Learning Objectives for Pharmacists:

Upon completion of this CPE course participants should be able to:

1. Discuss the role of inflammation in chronic disease.

2. Describe the impact of dysbiosis on gut integrity and chronic disease.

3. Explain the impact of selected nutrient deficiencies on chronic disease.

4. Identify key nutritional supplements that support overall wellness.

5. Develop care plans that incorporate nutraceutical products.

Learning Objectives for Pharmacy Technicians:

1. Discuss the role of inflammation in chronic disease.

2. Describe the impact of dysbiosis on gut integrity and chronic disease.

3. Explain the impact of selected nutrient deficiencies on chronic disease.

4. Identify key nutritional supplements that support overall wellness.

5. List nutraceutical products that may be incorporated into care plans.

Speaker: Melody Hartzler, PharmD, BCACP, BC-ADM

Melody Hartzler is a graduate of Ohio Northern Raabe College of Pharmacy and completed a

PGY-1 Pharmacy Practice Residency with emphasis in Ambulatory Care at the Chalmers P.

Wylie VA Ambulatory Care Center in Columbus, OH. Following residency, she joined faculty at

Cedarville University School of Pharmacy and developed a collaborative practice in a family

medicine residency program. She now serves part-time as an Associate professor of

pharmacy practice for Cedarville University School of Pharmacy and a clinical pharmacist at

Western Medicine Family Physicians. Her primary practice interests are diabetes, IBS/IBD,

and functional medicine. Currently, she works collaboratively with physicians through consult agreements. She

is a nationally recognized speaker and has presented 6 times at the ASHP Midyear Clinical Meeting as well as

numerous state and local programs. She is an active member of American Society of Health-System

Pharmacists and state and local organizations and a current board member for the Ohio Pharmacist

Association. Her passion for functional medicine led her to start PharmToTable, LLC. Her newest adventure is

FunctionalMedicineCE.com.

Speaker Disclosure: Melody Hartzler reports she is owner of PharmToTable, LLC. Off-label use of medications

will not be discussed during this presentation.

#RxExpo20

Recommending Supplements: Yes or No?

Melody L. Hartzler, PharmD, BCACP, BC-ADMCEO, PharmToTable, LLC

Director of Patient Care Services, Profero Team, LLC

Clinical Pharmacist, Western Medicine Family Physicians

Associate Professor of Pharmacy Practice, Cedarville University School of Pharmacy

#RxExpo20

Disclosure

• Dr. Hartzler reports:• Owner/CEO PharmToTable, LLC

1

2

#RxExpo20

Learning ObjectivesUpon successful completion of this course, participants should be able to:• Discuss the role of inflammation in chronic disease.• Describe the impact of dysbiosis on gut integrity and chronic

disease.• Explain the impact of selected nutrient deficiencies on chronic

disease.• Identify key nutritional supplements that support overall wellness.• Develop care plans that incorporate nutraceutical products (RPh)/

List nutraceutical products that may be incorporated into care plans (CPhT)

#RxExpo20

Inflammation, Dysbiosis, & Chronic DiseaseA Focus on Metabolic Disease

3

4

#RxExpo20

Chronic Disease Epidemic

Nutrition

Sedentary Lifestyles

Chronic Stress

Poverty

Environmental Toxicity

Fragmented Families &

Communities

Indoor Living (Vitamin D)

Aging Population

Adapted from Jones D, Quinn S. Introduction to FM. 2014 

#RxExpo20

One Condition Many Imbalances

Inflammation

Hormones

Genetics and Epigenetics

Diet and Exercise

Mood Disorders ObesityAdapted from Jones D, Quinn S. Introduction to FM. 2014 

5

6

#RxExpo20

Insulin Resistance & Inflammation

Reprinted with permission: Figure 4.  Guilliams, T. Cardiometabolic Risk Management: A Functional and Lifestyle Approach. The Standard Road Map Series.  Pointe Institute 2018.   

#RxExpo20

Functions of The Gut Microbiome

•Short Chain Fatty acids (SCFAs)

•Mucus

•Vitamin (Bs, K2)

• Enzymes

• Intestinal transit

• pH regulation

•Diversity

•Vitamins

•Minerals

•Glucose

•Hormone production

•Neurotransmitters

•Gut‐Brain messaging

•Inflammation

•Allergic response

•Epithelial barrier

•Pathogen exclusion

•Tight junctions

•Bacteriocin

Barrier Protection

Neuroendocrine Communication/

Immune Modulation

Nutrient Production

Digestive & Absorptive Functions

7

8

#RxExpo20

Triggers

• Food Allergy, Toxins, Stress, Dysbiosis

Intestinal Permeability

• LPS InflammationInflammatory Cytokines

Inflammation

#RxExpo20

GIT Microbiome… an endocrine organ?

Roles: 

� Carbohydrate digestion

� Hormone synthesis

� Neurotransmitter production

� Vitamin synthesis

� Immune response modulation

� Inflammatory response 

modulation

Food Intake

Metabolism EnergyHomeostasis

Galland L. J Med Food. 2014;17(12):1261‐1272Brown JM, et al. Annu Rev Med. 2015;66:343–359. 

9

10

#RxExpo20

Disease & The Microbiome

Cho I, Blaser MJ.  Nature Reviews Genetics. 2012;13(4):260‐270

#RxExpo20

Functional medicine approaches to address the underlying causes of metabolic disease• Address gut dysfunction

• Improve insulin sensitivity

• Supplements

• Exercise (Enhances uptake of glucose by

peripheral tissues, DPP Trial)

• Diet

• Address stress

• Consider anti‐inflammatory/cardiac risk reduction supplementation

Dr. Hartzler’s DM

Protocol! 

11

12

#RxExpo20

Nutritional Supplementation & Drug-Induced Nutrient DepletionsA focus on Vitamin D, Omega-3’s, and Probiotics

#RxExpo20

Nutritional Status

Guilliams T. Supplementing Dietary Nutrients. The Standard RoadMap Series. The Pointe institute. 2017. 

Type Description

Deficiency The intake of a nutrient is below the threshold required to maintain minimal physiological functionals required by that nutrient

Insufficiency Above a frank deficiency (where dz is present) but the level is still inadequate to maintain all necessary functions preformed by the nutrient

Adequate intake Prevents clinical or subclinical symptoms (adequate but no reserve)

Optimal Intake Adequate to satisfy needs and to overcome chronic or transient causes of functional insufficiency

Therapeutic Intake  Taking nutrients for a pharmacological vs. a physiological response

Excessive Intake When toxicity can result

13

14

#RxExpo20

Dietary Nutrient Considerations

• Nutrigenomics• The effect of nutrients on gene expression

• Nutrigenetics• How a person’s specific genetic sequences can affect their nutritional

needs and responses to nutrient intake

• Dietary Patterns• Food quality/Nutrient Density• Clean, Organic?

Guilliams T. Supplementing Dietary Nutrients. The Standard RoadMap Series. The Pointe institute. 2017. 

#RxExpo20

Testing for Nutritional StatusNutrEval is Genova's comprehensive nutritional evaluation and is designed to assist with management of symptoms related to nutritional deficiencies. This profile assesses numerous metabolic pathways and synthesizes this complex biochemistry into actionable treatment options. Critical nutrients that are functionally assessed on Genova's nutritional profiles include:

•Antioxidants•B Vitamins•Minerals•Essential Fatty Acids•Digestive Support

https://www.gdx.net/product/nutreval‐fmv‐nutritional‐test‐blood‐urine

15

16

#RxExpo20

Testing for Nutritional Status

SpectraCell’s Micronutrient test provides a comprehensive nutritional analysis available by measuring functional deficiencies at the cellular level. It is an assessment of how well the body utilizes 31 vitamins, minerals, amino/fatty acids, antioxidants, and metabolites, while conveying the body’s need for these micronutrients that enable the body to produce enzymes, hormones, and other substances essential for proper growth, development, and good health. Repletion recommendations are made based on need.

https://spectracell.com

#RxExpo20

Dietary Nutrient Considerations

• Addressing Nutrient Insufficiencies• Diet alone?• Diet plus supplementation?

17

18

#RxExpo20

Common Deficiencies

• Omega-3’s

• Vitamin D

• B-Vitamins

• Co-Q 10

#RxExpo20

Common Drug-Induced Nutrient DepletionsMedication(s) Nutrients

Anticonvulsants•Phenytoin•Carbamazepine

CalciumVitamin D

Folic acid

Biguanides•Metformin

Vitamin B12

Bile Acid SequestrantsVitamin AVitamin DVitamin K

Corticosteroids•Hydrocortisone•Prednisone

Calcium

Potassium

Medication(s) Nutrients

Estrogens•Oral contraceptives

Folic acid

H2‐Blockers Vitamin B12

Loop Diuretics Calcium

Loop Diuretics & Thiazide Diuretics

Potassium

MagnesiumThiamine

Thiazide Diuretics Zinc

Pancreatic Enzymes Folic acid

Proton Pump Inhibitors Magnesium

Statins Coenzyme Q10

https://naturalmedicines.therapeuticresearch.com/tools/charts/drug‐induced‐nutrient‐depletions.aspx

19

20

#RxExpo20

Resources for Drug Induced Nutrient Depletions• Natural Medicines Comprehensive Database

• MyTavin.com

• Drug-Induced Nutrient Depletion Handbook (Lexi-comp)

• The Nutritional Cost of Drugs (Pelton R & LaVelle J, RPh)

• Drug Muggers (Suzy Cohen, Rph)

• PharmaCE Replete

#RxExpo20

Vitamin D

21

22

#RxExpo20

What are common causes of Vitamin D

Deficiency?

● Low sunlight● Medications● Hepatic Failure● Renal Failure● Obesity● Malabsorption

1. Guilliams T. Supplementing Dietary Nutrients. The Standard RoadMap Series. The Point institute. 2017.2. Veith R, Holick M. Vitamin D 2018; 1:1091‐1107.  

#RxExpo20

Who should be screened for

Vitamin D Deficiency?

Patients with…MalnutritionSedentary LifestyleLimited sun exposureObesityDark skinAge ≥ 65Conditions causing gastrointestinal malabsorptionLiver disease or failureRenal insufficiency or nephrotic syndromeCystic FibrosisMedications that alter vitamin D metabolism (Ie anticonvulsants and glucocorticoids)

Vitamin D Deficiency. Slide Library.  AACE 2019. 

23

24

#RxExpo20

Who do I screen…

• EVERYONE• 2006 NHANES Data (Less than 20 ng/ml)

• All US adults 41.6% • African American 82.1%• Hispanics 69.2%

Vitamin D Deficiency. Slide Library. AACE 2019Forrest KY and Stuhldreher WL..Nutr Res 2011; 31:48‐54.

#RxExpo20

Case #1

• MJ is a 45 year old female with Type 2 DM, Obesity, HTN, and Asthma. She had her routine labs completed and is here for follow-up today. Her 25(OH)D level is 14 ng/ml.

• How would you classify MJ’s Vitamin D level? a) Deficient b) Insufficient c) Optimald) Toxic

25

26

#RxExpo20

Vitamin D Deficiency

• Consequences• Immune

• Respiratory Infections, Asthma, Wheezing

• Cardiovascular Dz• Metabolic Disease• Pre-eclampsia• Osteoporosis• Muscle weakness• Osteoarthritis• Osteomalacia• Rickets• Autoimmune

Category Level (ng/ml)

Deficiency <15

Insufficiency 15‐30

Minimum target 30

Therapeutic/Optimal 40‐70

Upper Limit 100

Excessive  >100

1. Guilliams T. Supplementing Dietary Nutrients. The Standard RoadMap Series. The Point institute. 2017.1. Veith R, Holick M. Vitamin D 2018; 1:1091‐1107.  

#RxExpo20

Vitamin D Supplementation Considerations• IOM intake recommendations are likely too low to reach optimal

target

• Obese adults required 2-3 times more vitamin D

• Repeat 25(OH) D levels 8-12 weeks after treatment

• Choose D3 form for supplementation

• Non-linear dosing• At low baseline levels, 1,000 IU daily will increase a patient by ~10

ng/ml• Higher baseline levels, more vitamin D will be needed to increase

levels the same amount. 1. Pludowski, et al. Journal of Steroid Biochemistry & Molecular Biology. 2018. 175: 125‐135. 2. Institute of Medicine. 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. 

https://doi.org/10.17226/13050.

27

28

#RxExpo20

Vitam

in D D

osingReference Neonates & under 

1 month1 month & Toddlers

Children 1‐18 y/o

Adults Intestinal malabsorption  or Obesity

Pludowskiet al. (Holick) 

1,000 IU/day 2‐3,000 IU/day

3‐5,000 IU per day

7‐10,000 IU per day or 50,000 IU per week

50,000 IU 2‐3 times per week. 

AACE (goal >30 ng/ml)

2,000 IU /day initial or 50,000 IU weekly for 6 weeks, then 400‐1,000 IU daily maintenance

2,000 IU/day for six weeks (or 50,000 IU weekly) ,then  600‐1,000 IU maintenance

6,000 IU per day or 50,000 IU per week for 8 weeks. Then maintenance therapy of 1,500‐2,000 IU/day.

6,000 to 10,000 IU per day for six weeks then 3‐6,000 IU daily

IOM‐DRI 400 IU/day 400‐600 IU/day

600 IU/day 600 IU (800 elderly) /day

Point Institute

1,000 IU/day 1,000 IU/day 1,000 IU/day 3,800‐5,000 IU/day

1,000 IU = 25 mcg1. Pludowski, et al. Journal of Steroid Biochemistry & Molecular Biology. 2018. 175: 125‐1352. Guilliams T. Supplementing Dietary Nutrients. The Standard. RoadMap Series. The Point institute. 2017.3. Holick MF et al. Evalua7on, treatment, and preven7on of vitamin D deficiency: an Endocrine Society clinical prac7ce guideline. J Clin Endocrinol Metab 2011; 96:1911‐30

#RxExpo20

A Note about Vitamin K2• Vitamin D3 regulates the amount of calcium and production of a

certain protein, osteocalcin, which plays a vital role in bone health once vitamin K2 activates it.

• Once activated, vitamin K2 then helps bind osteocalcin to calcium before directing the absorbed calcium to the bones, where it binds to the bone matrix to build bone and prevent its breakdown.

• Without vitamin K2, osteocalcin would remain inactivated and calcium would neither be able to bind to it nor reach its destination in the bones.

• As a result, it would be impossible for the body to build or strengthen bone to prevent against fractures or breaks.

Flore R, et al. Eur Rev Med Pharmacol Sci. 2013;17(18):2433‐2440.Villa JKD et al.  Crit Rev Food Sci Nutr. 2017;57(18):3959‐3970.

29

30

#RxExpo20

Vitamin K2 Considerations

• Choose the right vitamin K2: MK-7 is best due to it’s longer half-life, but a mixture of MK-4/MK-7 is fine.

• Pick an appropriate dose: Adults opt for at least 100 μg (MK-7) daily.

• Eat with fat: It is fat-soluble; intake with fat sources maximizes absorption.

• Consider Drug Interactions (ie Warfarin)

1. Shiraki et al.  J Bone Miner Res. 2000;15(3):515‐5212. Inaba N et al.  J Nutr Sci Vitaminol. 2015;61(6):471‐480. 

#RxExpo20

Case #1

• MJ is a 45 year old female with Type 2 DM, Obesity, HTN, and Asthma. She had her routine labs completed and is here for follow-up today. Her 25(OH) D level is 14 ng/ml.

• Which dose of Vitamin D3 would you recommend for MJ today to reach her optimal goal of >50 ng/ml? (In addition to at least 100 μg Vitamin K2 (MK-7) daily.)

a) 50,000 IU once weekly for 8 weeksb) 8,000 IU daily for 8 weeksc) 2,000 IU daily for 8 weeksd) A or B

31

32

#RxExpo20

Omega-3’s

#RxExpo20

Omega-3 Deficiency

• Standard American Diet (SAD)• Limited Omega-3• High in Omega-6

• The American Heart Association’s Strategic Impact Goal Through 2020 and Beyond recommends ≥ two 3.5-oz fish servings per week (preferably oily fish) partly to increase intake of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

• 2014 Study Few consumed appropriate levels

• Supplementation consider qualityPapanikolaou et al. Nutr J. 2014; 13: 31.

33

34

#RxExpo20

Omega-3• Supplement Forms

• rTG (re-esterified forms, monoglycerides, ethyl esters (EE), free fatty acids (FFA), or phospholipids

• Most commonly studied either EE or rTG• Superior bioavailability with rTG > EE forms

• DHA >EPA ?• DHA outperforms EPA in nearly every surrogate marker• DHA--> No clinical trials looking at MI, CVD, mortality• 1:1 likely a good ratio based on evidence• Most pharmaceuticals more EPA

• Icosapent ethyl CVOT Now approved for reducing CV events in adults with elevated TG

1. Guilliams, T. Cardiometabolic Risk Management: A Functional and Lifestyle Approach. The Standard Road Map Series.  Pointe Institute 2018.

2. Bhatt et al. N Engl J Med 2019; 380:11‐22

#RxExpo20

Omega-3 Types & Data

Guilliams, T. Differentiating the Therapeutic uses of EPA & DHA in Clinical Practice. Point Institute [White Paper] 2008.  

35

36

#RxExpo20

Probiotics & Prebiotics

#RxExpo20

Probiotics Defined  ● Live microorganisms which when administered in adequate amounts confer a health benefit on the host 3

Kechagia M, Basoulis D, Konstantopoulou S, et al. Health benefits of probiotics: a review. ISRN Nutr. 2013;2013:481651.

37

38

#RxExpo20

How do Probiotics Work?● While probiotics are most commonly associated with replacing

flora or colonizing the gut, modifications made to the gut microbiota are not likely permanent and reflect only one of many actions that probiotics have in the body.

● Among these actions are immune modulation, anti-inflammatory activity, pathogen antagonism, production of short chain fatty acids, repairing and strengthening of the intestinal barrier, metabolism of gut cholesterol, and enhanced antibody secretion.

Probiotic Advisor. The Importance of Strain. https://www.probioticadvisor.com/probiotic‐essentials‐1/the‐importance‐of‐strain/#.XC‐EEPZFxPZ. 

#RxExpo20

What is genus, species, and strain?

39

40

#RxExpo20

PrebioticsDefined

● “a non‐digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon.”

● Examples

○ Inulin, FOS, lactose, resistant starch, cellulose, hemicellulose, pectins, and gums

Gibson GR et al. J Nutr. 1995 Jun; 125(6):1401‐12.

#RxExpo20

Diseases Probiotics Have Been Studied with Positive

Effects

● Diarrhea

● Lactose Intolerance

● IBS

● Functional Constipation

● Allergic Rhinitis

● Asthma

● Eczema

● Diabetes

● Metabolic Syndrome

● IBD - Ulcerative Colitis

41

42

#RxExpo20

Probiotics & Prebiotics in Metabolic Disease

#RxExpo20

Probiotic Data in DiabetesStudies have shown…• Reduced glucose levels in postmenopausal women with metabolic

syndrome who received Lactobacillus plantarum verses those who did not1

• Improvements in A1C2,3

• Improvements in glucose, and insulin resistance3,4

• Reduction in weight gain4

• Multistrain species may have more impact than single strain5

1. Barreto FM et al. (meta‐analysis)2. Dolatkhah N et al Journal of Health, Population and Nutrition. 2015;33(1):25.3. Nikbakht E et al. Eur J Nutr. 2016:1‐12. (meta‐analysis).4. Dolatkhah N et al Journal of Health, Population and Nutrition. 2015;33(1):25.5. Nikbakht E et al.. Eur J Nutr. 2016:1‐12. (meta‐analysis)

43

44

#RxExpo20

Prebiotics

• “a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon.”

• Examples• Inulin, FOS, lactose, resistant starch, cellulose,

hemicellulose, pectins, and gums ( ie guar gum)

Gibson GR et al. J Nutr. 1995 Jun; 125(6):1401‐12.

#RxExpo20

Prebiotics• Study of healthy, non-diabetic individuals that received

supplementation with prebiotics (derived from chicory roots) for 2 weeks showed:

• An increase in plasma GLP-1 and a decrease in postprandial glucose compared to individuals that received the control (dextrin maltose supplementation).

• Prebiotic supplementation significantly lowered post-meal hunger scores and improved satiety scores.

Cani P, Lecourt E, Delzenne N, et al. Am J Clin Nutr. 2009;90(5):1236‐1243. 

45

46

#RxExpo20

Partially Hydrolyzed Guar Gum- Prebiotic

• Administration of 6 g/PHGG with each meal x 12 months1

• Lowered PPG, reduced both the fasting and postprandial insulin (IRI) and triglyceride (TG) levels (p = 0.05).

• Low-density lipoprotein (LDL) was lower, whereas high-density lipoprotein (HDL) level was significantly increased (p < 0.01). Plasma leptin, high-sensitive C-reactive protein (hs-CRP) and fasting glucagon like peptide (GLP-1) were also lowered.

• Stimulates bifidobacteria and butyrate-producing bacteria in the large intestine2

• Well tolerated compared to other pre-biotics

1. Kapoor M et al. Journal of Functional Foods. 2016; 24:201‐220.2. Ohashi Y et al. Benef Microbes. 20015;6(4):451‐5/.  

#RxExpo20

Specific Strains Studied for T2DM with Positive Benefits Strains Products

Lactobacillus acidophilus La5, Bifidobacterium lactis Bb12

Standard Process ProSynbiotic, Sogar (Various), Bayer(Various), Lamberts (Various). 

Lactobacillus acidophilus NCFM Metagenics (various), Garden of Life (Various), Florajen(various), Genestra (various), Nature’s Way (Various), Pharmax HLC Multi Strain, Olly Kids Quick Melt. 

A combination product. Various strains of 

Lactovacillus, Bifidobacterium, Lactococcus,) 

Institut AllergoSan Omni‐Biotic 60+ ActiveInstitut AllergoSan Omni‐Biotic Hetox Light

1. Ejtahed HS et al. Nutrition. 2012 May;28(5):539‐43.

2. Tonucci LB, et al. Clin Nutr. 2017 Feb;36(1):85‐92.

3. Mohamadshahi M, et al. J Res Med Sci. 2014 Jun;19(6):531‐6.

4. Andreasen AS,et al. Br J Nutr. 2010 Dec;104(12):1831‐8.

5. Sabico S, et al. J Transl Med. 2017; 15: 249.

47

48

#RxExpo20

Case #2• AT is a 45 y/o male with Type 2 DM.  He is active and working on incorporating diet and lifestyle modifications into his regimen. He struggles with constipation on and off.  His HbA1c is currently 7.3% and he would like it to be under 7%. Which of the following interventions would be something to consider for AT?

a) Prebiotic

b) Probiotic

c) Fiber

d) All of the above

#RxExpo20

Diarrhea

49

50

#RxExpo20

Diarrhea – Traveler's

• Saccharomyces cerevisiae variety boulardii (Biocodex strain)• 21% reduction in incidence of traveler's diarrhea in the 250mg/day

group (P<0.007) and 25% reduction with 500mg/day (P<0.002) compared to placebo. 1

• Meta-analysis of 2 RCTs (3280 participants) showed that Saccharomyces cerevisiae var boulardii supplementation (dosage range: 2.5 x 10^9 to 2 x 10^10 CFU per day), taken 5 days prior to travel and while traveling (mean duration of 23 days), showed a significant reduction in traveler's diarrhea incidence (RR=0.79, 95% C.I. 0.72–0.87, P<0.001). 2

1. Kollaritsch et al. Fortschr Med. 1993 Mar 30;111(9):152‐6.2. McFarland LV, et al. Travel Med Infect Dis. 2019 Jan ‐ Feb;27:11‐19

#RxExpo20

Diarrhea – Traveler's

• Combination of Lactobacillus acidophilus La5, and Bifidobacterium lactis Bb12

• Significantly fewer tourists given probiotics developed traveler's diarrhea. (43% vs 71%; P<0.001)1

• Nancy’s Organic Probiotic Greek Yogurt, Standard Process ProSynbiotic, Bayer Trubiotics

1. Black F.T et al. Travel Medicine. Springer, Berlin, Heidelberg. 1989. 

51

52

#RxExpo20

Acute Treatment- Children

• Combination product BioKult• In children ages 2 months to 2 years hospitalized from acute

gastroenteritis, probiotic group (standard treatment plus probiotic and FOS) showed a more rapid decrease in diarrhea rates (P<0.05 from days 2-4), a more rapid improvement in stool consistency, and an overall reduced length of hospital stay compared to control group (standard treatment only)1

1. Yala, ET. PIDSP Journal, 2010. 11 (2)

#RxExpo20

Acute Treatment- Children• Lactobacillus rhamnosus GG

• Subgroup analysis of RCTs revealed that LGG supplementation when compared with placebo, reduced the duration of acute rotavirus diarrhea in children by a mean difference of 0.47 days (CI 95% -0.80 to -0.14; P=0.020).1

• Hospitalized children with acute watery diarrhea were assigned to received oral rehydration solution alone (n=323) or with added LGG (120 million CFU daily; n=323) for a minimum period of 7 days or until diarrhea ceased. LGG did not promote any further decrease in the frequency and duration of diarrhea and vomiting or length of hospital stay relative to controls2

• Sources: Metagenics MetaKids Baby Probiotic, Culturelle Kids

1. Ahmadi, E et al. Caspian J Intern Med. 2015 Autumn; 6(4): 187–195.2. Basu S. et al J Paediatr Child Health. 2007 Dec;43(12):837‐42.

53

54

#RxExpo20

Antibiotic-Associated - Diarrhea -Prevention

• Saccharomyces cerevisiae variety boulardii (Biocodex strain)• Pooled data from randomized, controlled trials in children found ScB

co-administration to reduce the risk of antibiotic-associated diarrhea by 57% (RR=0.43; 95% CI 0.32-0.60.1

• Meta-analysis of 4 RCTs showed significant efficacy of Saccharomyces cerevisiae var boulardii) for the prevention of pediatric antibiotic-associated diarrhea (RR=0.43, 95% CI 0.21 to 0.86, I-squared = 79.1%).2

1. McFarland LV, Goh S. World J Meta‐Anal. Nov 26, 2013; 1(3): 102‐1202. McFarland, LV. Benef Microbes. 2015;6(2):189‐94. doi: 10.3920/BM2014.0034.

#RxExpo20

Antibiotic-Associated - Diarrhea -Prevention• Lactobacillus rhamnosus GG

•Pooled data from all RCTs (including both adult and pediatric patients) found LGG co-administration to be associated with a 60% reduced risk of antibiotic-associated diarrhea (RR=0.40; 95% CI 0.20-0.81).1

•Meta-analysis of 4 RCTs found that Lactobacillus rhamnosus GG has significant efficacy for the prevention of pediatric antibiotic-associated diarrhea. 2

•Sources: Culturelle Kids Probiotic Chews, Klaire Labs Culturelle, Metagenics UltraFlora Baby, Olly Quick Melt Probiotic stick, Mommy’s Bliss Probiotic Drops with D

1. Videlock EJ, Cremonini F. Aliment Pharmacol Ther. 2012 Jun;35(12):1355‐69..2. McFarland et al. Front Med (Lausanne). 2018; 5: 124.

55

56

#RxExpo20

Case #3

• KB is a 10 year‐old that was prescribed amoxicillin at your pharmacy today. Her mom says that the last time she took amoxicillin, she had terrible diarrhea and could not function well at school. Which of the following strains would be ideal for this patient?a) Lactobacillus rhamnosus GGb) Lactobacillus fermentum VRI‐003c) Lactobacillus plantarum 299vd) Lactobacillus acidophilus La5

#RxExpo20

Irritable Bowel Syndrome (IBS)

57

58

#RxExpo20

IBS Definition

Irritable bowel syndrome (IBS) is a disorder that affects the large intestine with symptoms that include cramping, abdominal pain, bloating, gas, and diarrhea or constipation, or a combination of the two.

https://www.mayoclinic.org/diseases‐conditions/irritable‐bowel‐syndrome/symptoms‐causes/syc‐20360016

#RxExpo20

IBS- Improvements in General Symptoms & QOL

• Lactobacillus fermentum VRI-003• Pharmanex ProBio PCC

• Lactobacillus plantarum 299v• Metagenics Ultra Flora Intensive Care,Nature’s Bounty Ultra Strength

Probiotic 10; GoodBelly Probiotic Drink)

• Combination Product known as ExeGI Pharm Visbiome VSL#3

1. Amansec, S. et al. Unpublished Research, 2005. Probiotic Advisor.2. Niedzielin K. Eur J Gastroenterol Hepatol. 2001 Oct;13(10):1143‐7.3. Ducrotté P, et al. World J Gastroenterol. 2012 Aug 14;18(30):4012‐4. Kim HJ et al. Neurogastroenterol Motil. 2005 Oct;17(5):687‐96.5. Kim HJ et al. Aliment Pharmacol Ther. 2003 Apr 1;17(7):895‐904.6. Ng SC et al. J Gastroenterol Hepatol. 2013 Oct;28(10):1624‐31.7. Dig Dis Sci. 2015 Jan;60(1):186‐94.

59

60

#RxExpo20

Other Strains/Products with data in IBSSpecies  Effect Products

Bifidobacterium bifidum CUL‐

20, Bifidobacterium lactis CUL‐

34 , Lactobacillus acidophilus 

CUL‐21, Lactobacillus 

acidophilus CUL‐60

Improvement in subjects global 

assessment of IBS symptoms.1Several Genesta and PharmmaxProducts

Soil Probiotics (specific blend) Was found to significantly 

decrease three broad categories 

of IBS symptoms ‐ general ill 

feelings/nausea, 

indigestion/flatulence, and 

colitis.2

Magnetic Clay Inc Prescript‐Assist

1. Williams EA et al. Aliment Pharmacol Ther. 2009 Jan;29(1):97‐1032. Bittner et al. Clinical Therapeutics 2007; 29 (6): 1153‐1160. .

#RxExpo20

Other Strains/Products with data in IBS

Species  Effect Products

Bacillus coagulans GBI‐

30 6086

Reduced severity of 

symptoms.1Schiff Digestive Advantage, Yoli Pure, Little Duck Organics, Goji Tiny Tummies

Lactobacillus reuteri

DSM 17938

Improved functional 

abdominal pain in 

children.2

BioGaia (several products), Gerber Soother Colic Drops, Yums

1. Hun L. Postgrad Med. 2009 Mar;121(2):119‐24.2. Jadrešin O  et al. J Pediatr Gastroenterol Nutr. 2017 Jun;64(6):925‐929.

61

62

#RxExpo20

Eczema/Atopic Dermatitis

#RxExpo20

Improvements in Eczema/Atopic Dermatitis

Species Products

Bifidobacterium lactis Bb12 Standard Process ProSynbiotic, Solgar Advanced Acidophilus, Metagenics (MetaKids) Baby Probiotic

Lactobacillus fermentum VRI‐003 Pharmanex Probio PCC

1. Isolauri E, et al. Clin Exp Allergy. 2000 Nov;30(11):1604‐102. Weston S, et al. Arch Dis Child. 2005 Sep;90(9):892‐7. Epub 2005 Apr 29.

63

64

#RxExpo20

Improvements in Eczema/Atopic DermatitisSpecies  Products

Lactobacillus acidophilus DDS‐

1, Bifidobacterium lactis UABLA‐12

UP4 (various)

Lactobacillus helveticus

R0052, Lactobacillus rhamnosus R0011

Xymogen Probio Defense & Lacidofil. Jarrow (Various), Natural Factors Relief Biotic

1. Gerasimov SV., et al. Am J Clin Dermatol. 2010;11(5):351‐61 2. Weston S, et al. Arch Dis Child. 2005 Sep;90(9):892‐7. Epub 2005 Apr 29.

#RxExpo20

Case #4

• PC is a 7 month old baby. She has had several food reactions as mom has started to give her solid foods. She also has eczema on her face and back. Which of the following strains should be recommended? a) Lactobacillus rhamnosus GGb) Lactobacillus fermentum VRI‐003c) Bifidobacterium lactis Bb12d) B & C

65

66

#RxExpo20

Frequently Asked Questions About Probiotics

#RxExpo20

If I have a milk or other food allergy, can I

take probiotics?

● Yes. A randomized controlled-trial found that supplementation with a probiotic helped infants allergic to cow’s milk develop a tolerance at a higher rate.

● Severe milk allergy patients should avoid probiotics made from milk. Dairy free probiotics are recommended for those with severe intolerance or allergy, where as dairy free would not be necessary for lactose intolerant patients.

Probiotic formula reverses cow’s milk allergies by changing gut bacteria of infants. The University of Chicago Medicine.https://www.uchicagomedicine.org/biological‐sciences‐articles/probiotic‐formula‐reverses‐cows‐milk‐allergies‐by‐changing‐gut‐bacteria‐of‐infants. Updated September 22, 2015.

67

68

#RxExpo20

If I have lactose

intolerance, can I take

probiotics?

● Yes. In fact, probiotics are being used to help those with lactose intolerance. In a review article examining the relationship between probiotics and their use in those with lactose intolerance it was found that there was an overall positive relationship.

● The species of bacteria that were most common among the reviews studied were lactobacillus acidophilus, lactobacillus bulgaricus, and streptococcus thermophilus all of which demonstrated some level activity.

Oak SJ, Jha R.. Crit Rev Food Sci Nutr. 2018;9:1‐9.

#RxExpo20

Should I take my probiotic

with or without food?

● A study looking at four species of bacteria found that survival through the GI tract was most preserved when given with a meal or 30 minutes before the meal.

● This may be due to the changes in acidity of the stomach during the fed and fasting states.

● During the fasting state, the stomach environment is more acidic, making it is more difficult for the bacteria to survive. Upon eating, however, the stomach environment becomes less acidic, thus providing a more favorable environment for bacteria to thrive.

Tompkins TA, Mainville I, Arcand Y.  Benef Microbes. 2011;2(4):295‐303.

69

70

#RxExpo20

What is the safety profile of probiotics?

● Studies have found that probiotics have minimal to no side effects. Side effects that are observed are most commonly bloating and flatulence, but the symptoms are mild and subside with continued use of the probiotic.

● Constipation and increased thirst have also been rarely associated with the species S. boulardii.

● The extreme side effects that have been found are in patients whose immune system have already been compromised.

Williams NT. Probiotics. Am J Health Syst Pharm. 2010;67(6):449‐58.

#RxExpo20

Case #5• DB is a 33 y/o male with Hx of IgG deficiency and is currently admitted for 

sepsis. The care team is considering probiotic to help prevent clostridium difficile. Is DB a good candidate for probiotics at this time? a) Yesb) No

71

72

#RxExpo20

Clostridium Difficile Infection (CDI) Guidelines• No recommendations for empiric use of probiotics- IDSA/SHEA

• Studies are small and have too much heterogeneity to come to a conclusion.

• Small Studies..• Support S Boulardii use in recurrent Cdiff. • A mixture of Lactobacillus acidophilus CL1285 and Lactobacillus casei

LBC80R (50 billion CFU) drastically reduced CDI rates in patients treated with antibiotics.

• Various other Lactobacillus combinations have been effective in small population studies.

1. Clostridium difficile IDSA/SHEA Guidelines. 2017. 2. J Clin Gastroenterol. 2011 November ; 45(Suppl): S154–S158.3. Gao X, et al.  Am J Gastroenterol. 2010; 105:1636–1641.

#RxExpo20

Why might my probiotic

cause diarrhea or

constipation?

● Diarrhea or constipation can occur with probiotics especially at the start of therapy due to multiple factors. Likely, it depends on the degree to which the gut is imbalanced to begin with, and as the gut is being rebalanced, bacteria can release by-products through fermentation that influence how fast the bowels move.

● Also, since the brain and gut appear to influence each other, lifestyle factors such as stress may influence the gut’s movement.

● While we do not know how each of these factors specifically affect the gut, there are multiple neurological influences by different types of bacteria which may contribute to the speed in which transit happens.

Conlon MA, Bird AR.. Nutrients. 2014;7(1):17‐44.

73

74

#RxExpo20

What if I can’t find a specific

strain?

● Trial and error is common with probiotics, low risk if we pick the wrong strain.

● If it doesn’t have a study, it doesn’t mean that it may not work. We just don’t know.

#RxExpo20

Other FAQs● Histamine Intolerance● Probiotics During Antibiotic Therapy● Small Intestinal Bacterial Overgrowth (SIBO)

● See Blog Post for further reading https://pharmtotable.life/2019/04/23/probiotic-faq-part-2/

75

76

#RxExpo20

Other Core Supplements & Nutrients● Metabolic Disease

○ Zinc 20 mg1,2

○ Berberine 500mg TID3,4

● Cardiovascular Disease & Inflammation

○ Curcumin5,6

○ Bergamot Flavanoids7,8

1. Ranasinghe P et al. Journal of Diabetes. Accepted Author Manuscript. doi:10.1111/1753‐0407.126212. Ranasinghe P et al.  Trials [serial online]. 2013;14:52.3. Yin et al. Metabolism 2008; 57(5):712‐7.4. Derosa et al. Expert Opin boil Ther. 2013; 13(4):475‐82.  5. Jiang, S et al. Pharmacological Research 119 (2017) 373–3836. Karuppagounder V, et al. Nutrition. 2017 Feb;34:47‐54. doi: 10.1016/j.nut.2016.09.0057. Cappello AR et al., Mini Rev Med Chem. 2016;16(8):619‐298. Giglio RV, et al. Phytomedicine. 2016 Oct 15;23(11):1175‐81.

#RxExpo20

Take Home Points• Gastrointestinal tract dysbiosis and inflammation contribute to

systemic inflammation and chronic disease.

• Prescription medications and poor dietary choices lead to nutrient depletions and insufficiencies.

• Addressing nutrient deficiencies is a role pharmacist can fill, especially when combined with medication related nutrient deficiencies.

• Omega 3’s, Probiotics, and Vitamin D are key supplements most of our patients need.

77

78