Yvette C. Terrie, BS Pharm, RPh

Clinical studies support the use of these supplements to promote health.

Probiotic supplements are commonly used to help maintain digestive balance and support a healthy immune system. Their popularity continues to increase as more new products are brought into the market.

For this reason, pharmacists should be prepared to answer patient questions regarding the selection and proper use of these supplements.

The Food and Agriculture Organization of the United Nations and the World Health Organization have defined probiotics as “live microorganisms which when administered in adequate amounts confer a health benefit on the host.”

 Probiotics are identified by their genus, species, and strain, and a variety of studies have investigated their health benefits.

Probiotic supplements are available in a range of dosage forms, such as capsules, tablets, and powders. Probiotics can also be found in fermented dairy products (ie, yogurt, yogurt drinks, and buttermilk), juices, soy products (ie, beverages and miso), and plant products (ie, sauerkraut). In both probiotic foods and dietary supplements, the bacteria may be naturally present or added during the preparation of the product.

Probiotics must withstand processing, storage, and delivery of the product and survive gastric acidity, bile acid lysis, and pancreatic enzyme digestion.

Furthermore, according to USProbiotics.org, the microbe must be alive when administered, must be documented to have a health benefit, and must be given at levels which demonstrate a health benefit.

Probiotic use has been linked to actions such as competition with pathogens for the binding sites on intestinal mucosa, reduction of intestinal permeability, changes in the intestinal pH, and direct antimicrobial activity against some pathogens.

The FDA does not currently regulate probiotic products. However, results of various clinical trials indicate that probiotics support general wellness and effectively treat a number of medical conditions that involve alterations in the normal flora of the intestines (ie, antibiotic-associated diarrhea/

—associated diarrhea, traveler’s diarrhea, and infectious diarrhea) as well as inflammatory and functional bowel conditions.

 Results of a recently published metaanalysis suggest that patients at risk of 

—associated diarrhea lowered their infection rate by 66% when prophylactic probiotics were administered.

 Probiotics have also been used to treat atopic dermatitis and allergies.

A number of ongoing studies are investigating how probiotics produce therapeutic benefits. Results from some of these studies suggest that probiotics may

		Boost the immune system by producing antibodies for certain viral illnesses

		Act as a barrier against bacteria or toxins in the intestinal wall

		Produce antibodies that may prevent infections

Some studies suggest that using probiotics may decrease the adverse effects often associated with the treatment of Helicobacter pylori infection as well.

Results from a study released in November 2012 by the American Heart Association reported that 2 daily doses of a probiotic decreased low-density lipoprotein cholesterol and total cholesterol in some patients with hyperlipidemia.

Another study published in December 2012 reported that the use of probiotics during pregnancy may help prevent infants from getting eczema.

Probiotic supplements may contain 1 or more different species from genera including 

 is the most prevalent strain found in the human body.

 Supplements currently on the market may contain Lactobacillus rhamnosus GG, reuteri, acidophilus, bulgaricus, and fermentum.

 Species of Bifidobacterium found in supplements include 

, which is a yeast, is the only species of 

 products are often recommended for antibiotic-associated diarrhea, and 

 GG is recommended for atopic dermatitis.

Two of the newest probiotic supplements on the market are Pfizer’s Pro Nutrients Probiotic supplement and Bayer HealthCare’s TruBiotics. Pro Nutrients is available in a powder formulation that can be added to cool foods or beverages. TruBiotics is available in capsule form that should be taken once a day. The capsule can also be opened and sprinkled onto cool food. Other available probiotic supplements are listed in the Table.

Patients electing to use probiotic supplements should be reminded to use products only from reputable companies and to adhere to the manufacturer’s dosage guidelines and directions for use. Pharmacists should advise patients—especially those with other medical conditions or those taking any prescription medications&mdash;to seek advice from their primary health care provider before using the supplements to ascertain whether it is appropriate to use them.

Patients with compromised immune systems should be advised not to use probiotics because of the potential for systemic infections.

 In addition, women who are pregnant or breast-feeding should be sure to seek advice from their doctors before using probiotic supplements. Clinical results are limited, but there are no reports of harmful results associated with the use of probiotics in late-term pregnancies or in those who are breast-feeding.

 Concurrent administration of probiotic supplements with any antibiotics or antifungal agents is typically not advised, and patients should be instructed to administer these agents at least 2 hours apart.

Probiotic supplements are typically well tolerated, although some patients may experience mild episodes of bloating and flatulence, which tends to decrease with continued use.

 In addition, diarrhea is often reported as a side effect of probiotic supplements in children.

 Patients who experience severe episodes of diarrhea or other side effects should be encouraged to seek advice from their primary health care provider. Since some probiotic supplements contain lactose, patients who have milk allergies or who are lactose intolerant should avoid using dairy-based supplements. To minimize side effects, the supplements should be taken with cool or room temperature food or drink at the same time each day.

Ms. Terrie is a clinical pharmacy writer based in Haymarket, Virginia.

		Joint FAO/WHO Working Group on Drafting Guidelines for the Evaluation of Probiotics in Food. Guidelines for the evaluation of probiotics in food. ftp://ftp.fao.org/es/esn/food/wgreport2.pdf. Accessed January 15, 2013.

		Oral probiotics: an introduction. National Center for Complementary and Alternative Medicine website. http://nccam.nih.gov/health/probiotics/introduction.htm. Accessed January 2, 2013.

		Probiotics: a consumer guide for making smart choices. International Scientific Association for Probiotics and Prebiotics website. www.isapp.net/docs/Consumer_Guidelines-probiotic.pdf. Accessed January 2, 2013.

		Probiotics: take a closer look. Phillips Colon Health website. http://phillipspro.com/static/documents/pdf/PCH-47109_M2_Advertorial_PO.pdf. Accessed January 2, 2013.

		Rollins C. Functional and meal replacement foods. In: Berardi R, Newton G, McDermott JH, et al, eds. Handbook of Nonprescription Drugs. 16th ed. Washington, DC: American Pharmacists Association; 2009:433-434.

		Williams N. Probiotics. Medscape website. www.medscape.com/viewarticle/719654. Accessed January 2, 2013.

		Ciorba M. A gastroenterologist’s guide to probiotics. Medscape website. www.medscape.com/viewarticle/770468. Accessed January 2, 2013.

		Probiotic Basics. USProbiotic.org website. http://cdrf.org/home/checkoff-investments/usprobiotics/probiotics-basics/. Accessed January 2, 2013.

		Michail S et al. Clinical efficacy of probiotics: review of the evidence with focus on children. 

		Johnston BC et al. Probiotics for the prevention of Clostridium difficile associated diarrhea: a systematic review and meta-analysis. 

		Probiotics: What they are and what they can do for you. American Gastroenterological Association website. www.gastro.org/patient-center/diet-medications/probiotics. Accessed January 2, 2013.

		An introduction to probiotics, get the facts. National Center for Complementary and Alternative Medicine website. http://nccam.nih.gov/health/probiotics. Accessed January 2, 2013.

		Daily doses of a new probiotic reduces HDL cholesterol. American Heart Association website. http://newsroom.heart.org/news/daily-doses-of-a-new-probiotic-239562. Accessed January 2, 2013.

		Foolad N, Brezinski EA, Chase EP, Armstrong AW. Effect of nutrient supplementation on atopic dermatitis in children: a systematic review of probiotics, prebiotics, formula, and fatty acids. 

		McQueen C. Nonbotanical natural medicines. In: Berardi R, Newton G, McDermott JH, et al, eds. Handbook of Nonprescription Drugs. 16th ed. Washington, DC: American Pharmacists Association; 2009:992.

Articles

Probiotics: Harnessing the Power of Good Bacteria

As vitamin D deficiency gets more attention in the media, patients turn to supplements.

Researchers regularly turn up new findings regarding the role played by vitamin D in overall health. As a result, interest in vitamin D supplementation has surged in recent years.

In the United States, the sale of vitamin D supplements increased from $42 million to $605 million between 2002 and 2011.

Yet many individuals still suffer from low vitamin D levels. According to the Centers for Disease Control and Prevention, between 2001 and 2006, approximately two-thirds of the population had sufficient vitamin D levels, one-fourth were at risk of vitamin D inadequacy, and 8% were at risk of a vitamin D deficiency.

Vitamin D is a fat-soluble vitamin whose primary biologic function is to maintain normal blood levels of calcium and phosphorus.

 It has properties of both a vitamin and a hormone. It aids in the absorption of calcium in the gut and assists in maintaining sufficient serum calcium and phosphorus levels to allow for normal mineralization of bones.

 Maintaining an adequate level of vitamin D helps decrease the risk of fractures from falls.

 provides more interesting facts about vitamin D. 

Most people obtain a sufficient amount of vitamin D through diet and exposure to sunlight. Some are at greater risk for vitamin D deficiencies, however, especially during the winter months, when sun exposure is limited (Table 2

 Patient populations that may be at elevated risk for vitamin D deficiencies include the elderly, obese individuals, exclusively breast-fed infants, and those who have limited sun exposure.

In addition, individuals who have fat malabsorption syndromes, such as cystic fibrosis or inflammatory bowel disease, including Crohn’s disease, are at risk for vitamin D deficiency.

 The use of medications such as phenytoin and carbamazepine may increase the metabolism of vitamin D and reduce calcium absorption.

 On the other hand, patients taking corticosteroids may experience impaired metabolism of vitamin D and should be monitored for adequate vitamin D levels.

Clinical studies have associated vitamin D deficiency with autoimmune disorders, cardiovascular disease, cancer, musculoskeletal decline, dementia, infectious disease, and depression.

 outlines recent research on the impact of vitamin D on health.

In recent years, there has been a great deal of debate about vitamin D supplementation and the proper recommended dietary allowance (RDA) for this vitamin. The Institute of Medicine (IOM) recommends an RDA of 400 IU of vitamin D for children younger than 1 year, 600 IU for those aged 1 to 70 years, and up to 800 IU for those 71 years and older.

The IOM also recommends an upper limit of 4000 IU per day.

The IOM points out, however, that higher doses may be necessary for those with osteoporosis or vitamin D deficiency.

 The IOM has concluded that a vitamin D level of 20 ng/mL should be considered adequate and that the long-term safety and potential adverse effects of levels above 50 ng/mL is unknown, although emerging evidence suggests potential adverse effects at this level or higher.

In May 2012, the US Preventive Services Task Force recommended supplementation of 800 IU of vitamin D per day for those at risk for falls or fractures.

 The Endocrine Society’s clinical practice guideline on vitamin D deficiency suggests that an RDA of 400 to 1000 IU may be needed for children 1 year and older and 1500 to 2000 IU may be required for those 19 years and older.

 The guidelines also state that current clinical evidence suggests that children and adults should maintain a vitamin D level of at least 20 ng/mL to prevent rickets and osteomalacia.

The guidelines further state that in order to maximize vitamin D’s effect on calcium, bone, and muscle metabolism, the vitamin D level should be at least 30 ng/mL. Numerous epidemiologic studies have suggested that a vitamin D level of at least 30 ng/mL may also decrease the risk of type 2 diabetes and cardiovascular disease, as well as certain cancers, autoimmune diseases, and infectious diseases.

 In January 2011, the American Academy of Dermatology updated its position statement on vitamin D so that it was in agreement with the IOM’s recommendations.

Vitamin D supplements are available as single-entity products or as products that combine vitamin D with calcium; vitamin D is also included in many multivitamins. These supplements are available in dosage forms including liquid, capsules, tablets, and sublingual tablets to meet the needs of different patient populations.

Patients should be encouraged to consult with their primary health care provider prior to taking these supplement products because they may already be getting an adequate amount of vitamin D through diet, sun exposure, and multivitamin supplements containing vitamin D. When recommending vitamin D supplementation, vitamin D

, the natural form, is preferred over vitamin D

 because it is more effective at maintaining adequate levels in the human body.

Patients suspected of having a nutritional deficiency should always be referred to their primary health care provider for further medical evaluation prior to recommending the use of these supplements. In addition, pharmacists are in a pivotal position to identify patients at risk for possible drug—nutrient interactions and should make clinical recommendations accordingly.

During counseling, pharmacists should remind patients to adhere to recommended dosages unless otherwise directed by their primary health care provider. Patients should also be reminded to check the content of vitamin D in any other supplements that they may be taking to avoid possible toxicity, keeping in mind that the recommended daily upper limit for vitamin D is 4000 IU.

Vitamin D toxicity is rare, but patients experiencing any of the signs associated with it should immediately consult their primary health care provider. These signs include weakness, anorexia, headache, somnolence, nausea, vomiting, dry mouth, a metallic taste, constipation, and muscle or bone pain.

 Vitamin D toxicity may also cause kidney stones, hypercalcemia, or renal failure.

 Patients should always be encouraged to discuss the use of vitamin D supplements with their primary health care provider to ascertain what is best for their individual health needs.

Ms. Terrie is a clinical pharmacy writer based in Haymarket, Virginia

		Has Vitamin D been oversold? AARP website. www.aarp.org/health/drugs-supplements/info-07-2012/how-much-vitamin-d-is-enough.html. Accessed January 5, 2013.

		Vitamin D status: United States 2001-2006. Centers for Disease Control website. www.cdc.gov/nchs/data/databriefs/db59.htm#findings. Accessed January 5, 2013.

		Huckleberry Y, Rollins C. Essential and conditionally essential nutrients. In: Krinsky D, Berardi R, Ferreri S, et al, eds. Handbook of Nonprescription Drugs. 17th ed. Washington, DC: American Pharmacists Association; 2012.

		Vitamin D. Medline Plus website. www.nlm.nih.gov/medlineplus/druginfo/natural/patient-vitamind.html. Accessed February 18, 2013.

		Barclay L. Management of vitamin D deficiency reviewed. Medscape website. www.medscape.com/viewarticle/712007. Accessed January 8, 2013.

		Dietary supplement fact sheet: vitamin D. National Institutes of Health Office of Dietary Supplements. http://dietary-supplements.info.nih.gov/factsheets/vitamind.asp#h9. Accessed January 5, 2013.

		Vitamin D. Merck Manual for Healthcare Professionals Online Edition. www.merckmanuals.com/professional/nutritional_disorders/vitamin_deficiency_dependency_and_toxicity/vitamin_d.html. Accessed January 5, 2013.

		Vitamin D supplementation. Centers of Disease Control and Prevention website. www.cdc.gov/breastfeeding/recommendations/vitamin_d.htm. Accessed January 5, 2013.

		Haines ST, Park SK. Vitamin D supplementation: what’s known, what to do and what’s needed. 

		Pramyothin P, Holock MF. Vitamin D supplementation: guidelines and evidence for subclinical deficiency. 

		Dietary reference intakes for calcium and vitamin D. Institute of Medicine website. www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Report%20Brief.pdf. Accessed January 4, 2013.

		Evaluation, treatment and prevention of vitamin D deficiency clinical guidelines. The Endocrine Society website. www.endo-society.org/guidelines/final/upload/final-standalone-vitamin-d-guideline.pdf. Accessed January 4, 2013.

		Updated position statement on vitamin D. American Academy of Dermatology website. www.aad.org/stories-and-news/news-releases/academy-issues-updated-position-statement-on-vitamin-d. Accessed January 3, 2013.

		Vitamin D levels linked to daytime sleepiness. Medline Plus website. www.nlm.nih.gov/medlineplus/news/fullstory_132264.html. Accessed January 5, 2013.

		McCarty DE, Reddy A, Keigley Q, Kim PY, Marino AA. Vitamin D, race, and excessive daytime sleepiness. 

		Low vitamin D levels linked to more severe MS symptoms. John Hopkins news release website. www.hopkinsmedicine.org/news/media/releases/low_vitamin_d_levels_linked_to_more_severe_multiple_sclerosis_symptoms. Accessed January 5, 2013.

		Kjaergaard M, Eggen AE, Mathiesen EB, Jorde R. Association between headache and serum 25 hydroxyvitamin D [published online September 13, 2012]. 

		McAlindon T, LaValley M, Schneider E, et al. Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis. 

Vitamin D: Are Your Patients Getting Enough?

For patients who have reservations about flu vaccination, this guide can ease concerns.

According to the Centers for Disease Control and Prevention (CDC), the 2012-2013 influenza season has reached epidemic proportions due to the high number of flu-related deaths reported so far. Escalating rates of infection have marked it as one of the worst influenza outbreaks in nearly a decade.

The influenza virus is serious—and contagious&mdash;and it can lead to hospitalization and even death. This is especially true among children and the elderly, due to complications such as pneumonia, otitis media (middle ear infection), sinus infections, and dehydration. The flu can also make certain medical conditions worse. The good news is that there are things you can do to reduce or even prevent the spread of the influenza virus.

Getting a flu vaccine every year is still the best way to protect against the flu. The flu vaccine can reduce risk of illness and complications and prevent the spread of the virus, especially to infants younger than 6 months, who cannot be vaccinated.

The CDC urges people older than 6 months to get an influenza vaccine every year. It’s best to get a flu vaccine before the season begins. After vaccination, it takes about 2 weeks for the body to develop antibodies to provide protection. Flu season can begin in October or November, and it typically peaks in January or February. But it is never too late to get vaccinated during the flu season.

Vaccination is especially important for those at risk for flu complications, including the elderly, children, pregnant women, and individuals with certain medical conditions (including asthma, diabetes, or cardiovascular disease). Flu vaccination is available in different forms. The inactivated vaccine comes in an injectable form—the flu shot&mdash;and is approved for people 6 months and older. The live attenuated vaccine is administered intranasally (through the nose), and is approved for healthy people aged 2 to 49 years who are not pregnant.

After getting flu vaccination, you may experience soreness or low-grade fever. If you had a flu shot, you might notice tenderness or swelling at the injection site. After the intranasal vaccine, people sometimes have slight nasal congestion.

Unfortunately, many people shy away from getting the flu vaccine because of this common myth. The CDC says that because the injection contains an inactivated virus, it cannot cause the flu. While the nasal form of the vaccine does contain live viruses, they are very weak and cannot cause the flu either.

The CDC recommends that you should not be vaccinated without first consulting a doctor if:

		You have a severe allergy to chicken eggs

		You had a severe reaction to influenza vaccination in the past

		You have a history of Guillain-Barré syndrome (your doctor will determine whether the vaccine is right for you)

In addition to vaccination, preventive measures against the flu are easy and straightforward. The flu can be transmitted through the air when a sick person coughs or sneezes, by direct contact with an infected person, or through contact with contaminated objects. Routine hand-washing and covering your coughs and sneezes in your elbow or a tissue are critical steps against the transmission of the flu. Also avoid touching your eyes, nose, or mouth, because germs are easily spread this way.

If you do get the flu, your doctor may prescribe antiviral drugs to lessen the severity of the flu or to prevent complications. Also get plenty of rest and stay hydrated. If you are sick, stay home and limit exposure to others, especially if you have a fever.

Knowing the facts about the flu and the flu vaccine and dispelling common myths can help you make informed decisions about your health. Remember, getting vaccinated annually is your best defense in combating the influenza virus. Talk with your doctor or pharmacist about what is best for your health.