herbs recommendations

8/22/2019 Herbs Recommendations

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2013 by the American Pharmacists Association. All rights reserved.

Evidence-BasedRecommendations for

Herbal and DietarySupplements

Bella H. Mehta, PharmD, FAPhA

The Ohio State University

Tommy Johnson, PharmD, BC-ADM, CDE, FAADE

Presbyterian College School of Pharmacy

22

Supporter

Procter and Gamble

44

Disclosures Tommy Johnsondeclares no conflicts of interest, real or

apparent, and no financial interests in any company, product, orservice mentioned in this program, including grants,employment, gifts, stock holdings, and honoraria

Bella Mehta is on the speakers bureau for Amerisource Bergenand Cardinal Health and is a stockholder for Pfizer

The American Pharmacists Association is accredited by theAccreditation Council for Pharmacy Education as a provider of continuing

pharmacy education.55

Target Audience: Pharmacists

ACPE#: 0202-0000-13-017-L04-P

Activity Type: Knowledge-based

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Learning Objectives

At the completion of this activity, participants will beable to:

Summarize federal regulations governing dietarysupplements

Identify dietary supplements that can berecommended based on available evidence, as well asdietary supplements whose safety and efficacy are not

supported by available evidence List adverse effects, clinically important druginteractions, and other cautions associated withcommonly used dietary supplements

Outline a strategy for guiding patient selection and useof dietary supplements

Provide examples of reputable sources of evidence-based information about dietary supplements

77

Which of the following regulations

requires manufacturers to report

serious adverse effects of herbs and

dietary supplements?

A. Dietary Supplement Health andEducation Act of 1994

B. Federal Food Drug andCosmetic Act

C. Dietary Supplement andNonprescription ConsumerProtection Act

D. Kefauver Harris Amendment


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88

A pat ient wi th d ysl ip idemia wan ts to start

omega-3 fatty acids. His profile show s

elevated LDL, elevated trigl ycerides and at

goal HDL. Which of the follow ing doses ofomega-3 fatty acids woul d you tell him is most

effective for him to reach target lipid goals?

A. 1 gram per dayB. 4 grams per dayC. More is betterso he

should take as much ashe can tolerate

D. None of the above,omega-3 fatty acids willnot be beneficial forthis patient

99

What Vitamin is fat soluble, necessary

for proper eye function and may

increase bone fractures if taken in

excess?

A.Vitamin AB.Vitamin B1C.Vitamin CD.Vitamin D3

1010

What is a reputable resource for

finding info rmation about the uses,

doses and potential side effects of

herbs, vitamins and supplements?

A. National InquirerB. Natural StandardC.Vitamin KingdomD.Happy Hempster

Health Highlights

1111

Do you currently use herbs

and/or d ietary supplements?

1.Yes2.No

1212

Background

Three-fourths of world relies on natural medicines JAMA study1

1990 - 34% used > 1 alternative therapy

1997 - 42% used > 1 alternative therapy

Current use approximately 40-62%2,3

$34 billion spent out of pocket annually on CAM3

Products, classes, visits to providers $15 billion spent on herbs and dietary supplements3

29,635 supplement-related health problemsreported to poison control centers in 20094

1.Eisenberg et al.JAMA 1998;280:1569-75.2.Barnes PM et. CDC Advance Data from Vital and Health Statistics No 343; May

20043.Barnes PM et al. CDC National Health Statistics Report No 12; Dec 2004.4.Clinical Toxicology Dec 2010, Vol. 48, No. 10: 9791178. 1313

Trends in Consumer Use of

Herbs/Dietary Supplements

In 2007: CDC survey reported 17.7% of Americansused a natural product in the previous 12 months

According to the 2007 CDC survey, use of CAMwas most prevalent in:

Women

Adults ages 30-69 years

Patients with higher level of education

Patients that are not poor

Adults that were hospitalized in the past year

Children whose parents used CAM

Barnes PM et al. CDC National Health Statistics Report No 12; Dec 2008


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Popular Herbs and Dietary Supplements:

2007 National Health Survey

Fish oils/omega-3 Fatty acids

Glucosamine

Echinacea

Flaxseed

Ginseng

Combination pills

Gingko biloba

Chondroitin

Garlic

Coenzyme Q10

Fiber/psyllium

Green tea pills

Cranberry pills

Saw palmetto

Soy

Melatonin

Grape seed extract

Methylsulfonylmethane(MSM)

Milk thistle

Lutein

Barnes PM et al. CDC National Health Statistics Report No 12; Dec 2008 1515

2011 Harvard Opinion Research Program Conducted telephone survey of 1579 respondents Approximately 4 out of 10 Americans reported using

supplements in past 2 years

Reasons for use: To feel better

To improve overall energy levels

To boost immune system

36% had not told physician about use of supplements

5% had been told by physician or nurse to stopsupplement

25% reported that they would stop using supplement ifpublic health authorities found it was ineffective

Trends in Consumer Use of

Herbs/Dietary Supplements

Blendon RJ et al. Arch Intern Med. 2012; doi:10.1001/2013.jamainternmed.311

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Popular Herbs and Dietary

Supplements: 2011 Harvard Survey

Fish oils or omega-3 supplements

Herbal supplements like ginseng

Probiotics like acidophilus

Any other supplements like amino acids, algaederivatives or combination products

Supplements derived from foods like garlicsupplements

Blendon RJ et al. Arch Intern Med. 2012; doi:10.1001/2013.jamainternmed.311

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REGULATIONS OF HERBS

AND DIETARY

SUPPLEMENTS

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Regulatory Role of FDA

FDA responsible for taking action against anyunsafe dietary supplement product after it reachesthe market

Post-marketing responsibilities: Monitoring safety

Product Information

Labels

Claims

Package insert

Accompanying literature

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Overview o f Regulations

1951: 2 classes of drugs were established(prescription and non-prescription (OTC))

1962: Kefauver-Harris Amendment

1994: Dietary Supplement Health and EducationAct (DSHEA)

2006: Dietary Supplement and NonprescriptionDrug Consumer Protection Act

June 22, 2007: New Dietary Supplement CurrentGood Manufacturing Practices (cGMPs) Final RuleIssued by FDA


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DSHEA

Signed into law on October 25, 1994 Herbal supplements, vitamins and mineralsconsidered dietary supplements not drugs

Dietary ingredients in supplements no longersubject to pre-marketing safety evaluations

Labeling criteria Body structure and function claims Cannot make therapeutic claims Must state not approved by FDA Must have manufacturers name and address Not required to have lot numbers, expiration dates or

contraindications

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Dietary Supplement and

Nonprescription Drug Consumer Act

Passed by Congress on 12/26/06; effective12/26/07 Known as the Adverse Event Reports Bill (S. 3546) Amends the Federal Food Drug and Cosmetic Act

and requires manufacturers to report seriousadverse events for OTC drugs and dietarysupplements

Requires manufacturers to submit report of adverseevent within 15 business days of receipt

Requires labels to have address or phone numberso that patients can report serious adverse events

2222

HERBS AND DIETARY

SUPPLEMENTS

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Herbs and Dietary Supplements

Omega-3 fatty acids (fish oil, krill oil)

Green coffee extract

Raspberry ketones

Butterbur

Feverfew

Probiotics

Vitamins and Minerals Vitamins A, C, D, and E

Niacin

Minerals: calcium, iron, magnesium, zinc

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Fish Oils (Omega-3 Fatty Acids)

Background Can consume in diet th rough cold water fish that are high in

omega-3 fatty acids or through other natural products likeavocado or almonds (alpha-linolenic acid)

Krill oil has significantly lowe r concentration s of omega-3fatty acids

Uses: High triglycerides Reduction in risk of de ath from heart dise ase

Treatment of various ca ncers Mechanism:

May have anti-inflammatory and blood thinnin g effects May have vasodilatory and anti-arrhythmic effects Constituents are omeg a-3 fatty acids EPA and DHA May prevent weight los s of cancer and may s low cancer

growth

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Summary of clinical studies High triglycerides

Reduces triglycerides by 20-50%

Slight increase LDL; negligible increase in HDL

Dose: 2-5 grams (EPA+DHA) per day

Primary prevention of heart disease

May decrease risk of coronary heart disease death by 25%in healthy patients with long term use

Dose: 1 gram daily (EPA+DHA) or 1-2 servings per week Secondary prevention of heart disease

Showed 15% reduction in risk of total cardiac event, non-fatal MI, and total cardiac mortality in patients who had an MI

Additional studies showing 16-23% reduction in overallmortality plus reduction in MI by 20-30%

Dose: 1-10 grams daily (EPA + DHA)


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Currently some controversies aboutcardioprotection

Meta-analysis of 20 studies on omega-3 fatty acids 2012 JAMA1

Found no statistical significance in all-causemortality

OPERA trial and FORWARD trial 2,3

Considerations of older vs. newer studies: Patient populations

Utilization of lipid lowering medications

Overall knowledge about lifestyle changes1. Rizos EC et al. JAMA. 2012;308(10):1024-1033

2. Marchioli et al. JAMA. 2012;308(19):2001-2011.

3. Macchia et al. J Am Coll Cardiol. 2013 Jan 29;61(4):463-8 2727


Patient Recommendation

Patient with no coronary heartdisease (CHD)

Eat a variety of fish 2 times perweek; include alpha-linolenic acidfoods in diet

Patient with documented CHD Consume 1 gram of EPA + DHAper day through food sources orsupplement (with doctor)

Patient with high triglycerides Take 2-4 grams per day of EPA +DHA through supplements inconsultation with doctor

American Heart Association Recommendations

Adapted from table 5: Kris-Etherton et al. Circulation 2002; 106;2747-2757.

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Other uses for omega-3 fatty acids: Prevention of restonsis from angioplasty

Asthma

Heart failure

Stroke

At high doses can increase risk

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Example Fish Oils (Omega-3

Fatty Acids) Label

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Lovaza (formerly Omacor) FDA approved omega-3 fatty acid

Indicated as adjunct treatment to diet for treatment ofhypertriglyceridemia

Most effective with TG >500mg/dL

Contains 465mg EPA and 375mg DHA in 1 gram

capsule Dose: 4 grams daily

Vascepa (icosapent ethyl) FDA approved omega-3 fatty acid soon to be on

market

Indicated as adjunct treatment to diet for treatment ofhypertriglyceridemia

Most effective with TG >500mg/dL3131


Important Adverse Effects Fishy aftertaste

Diarrhea, flatulence, belching

Risk of stroke with high dose (> 46 grams/day)

Patient counseling suggestions to minimize adverseeffects:

Consider using enteric coated formulations Start at low dose and titrate up over several weeks

Counsel pregnant patients and young children tolimit consumption of fish oils

12 ounces per week for pregnant patients

2 ounces per week for young children


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Important Drug Interactions Contraceptives may decrease the triglyceride

lowering effect of fish oils

May increase risk of bleeding with antiplatelets andanticoagulants with high dose fish oils

Orlistat decreases absorption of fish oils

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Fish Oils (Omega-3 Fatty Ac ids)

Summary

Included within American Heart Associationguidelines as potentially beneficial for: Triglyceride lowering

Preventing cardiac events in healthy patients

Decreasing risk of total cardiac events, second MI andtotal cardiac mortality in patients that have had an MI

Titrate the dose increase slowly

FDA approved product is available

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Patient Case #1

One of your regular patients is in the herbs and vitamins aisleand is holding 2 bottles in his hand one is EcoKrill tablets(EPA 65mg,DHA 35mg, other omega-3) and the other bottle isIceland Health Omega Ultimate (EPA 400mg and DHA300mg). He wants to know what you would recommend thathe take. You take out his chart and see the following:

Medications:Altace (ramipril) 5mg once daily, Zocor

(simvastatin) 40mg once every evening, Aspirin 325mg oncedaily, Coumadin (warfarin) 5mg once daily

Past Medical History: HTN x 5 years (at goal),Hyperlipidemia x 5 years (at goal); Atrial fibrillation x 2 years(INR at goal)

Family History: Brother had a heart attack at age 40 years;

Father died of heart attack at 82 years old3535

Which product will you recommend?

1. EcoKrill2. Iceland Health

Omega Ultimate

3. Neither would helphim

3636

What would be the

recommended dose?

1.1 gram daily2.4 grams daily3.As much as he

can tolerate

4.None of theabove wouldnotrecommend

3737

Key points

This patient has lipid profile at goal and has astrong family history of cardiac disease but has nothad an event himself

Select cardioprotective dose of fish oils vs.triglyceride lowering dose

Could also educate about dietary sources of fish

oils vs. supplements


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Green Coffee Extract

Background Dr. Ozs Green Coffee Bean Project

Uses

Weight loss

Cardiovascular conditions including high blood pressure

Type 2 Diabetes

Infections

Mechanism

Coffee beans that are not roasted so higher in chlorogenicacid

Thought to have modulating effects on glucosemetabolism

Thought to inhibit fat accumulation

Thought to have antihypertensive effect3939


Summary of Clinical Studies Weight loss GCA extract of 700mg or 1050mg showed 1.5-2kg weight

loss over 6 weeks

Svetol extract showed 2.5kg weight loss vs. placebo

Hypertension Svetol extract reduced systolic blood pressure by 5-6

mmHg and diastolic blood pressure by 3-4 mmHg

Dr. Oz Project 100 women between 35-49 years old that had BMIs of

25-45

Green coffee extract 400mg three times per day vs.placebo

In 2 weeks, green coffee extract lost 2 pounds vs. 1pound on placebo

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Major Adverse Effects Well tolerated with no adverse effects in clinical trials

Theoretical effects would those related to caffeine

Insomnia, diuresis, gastric distress, headache, anxiety,agitation

Major Drug Interactions Mostly theoretical drug interactions with caffeine

Examples: antihypertensive agents, cimetidine,stimulants

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Raspberry Ketones

Background Also featured on Dr. Oz segment

Flavoring agent

Uses Alopecia

Weight loss, obesity

Increasing lean body mass

Mechanism May increase lipid metabolism and reduce obesity by

increasing norepinephrine-induced lipolysis andthermogenesis

May increase skin insulin-like growth factor-1

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Raspberry Ketones

Summary of Clinical Studies Very little research has been done

Preliminary studies show raspberry ketones mayhave some benefits hair growth in patients withalopecia

May promote weight loss and help with obesity

Raspberries (not the ketone component) beingevaluated for anti-cancer properties

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Raspberry Ketones

Major Adverse Effects Concern that it may have stimulant effects like

synephrine

Theoretically similar structure to capsaicin

No reliable information for human use

Major Drug Interactions

Warfarin

Potential interactions with antineoplastic agents


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Butterbur

Background Perennial shrub whose leaves have been used for

over 2,000 years

Uses Prevention of allergic rhinitis

Migraine prophylaxis

Asthma

Mechanism of action Thought to decrease concentration of antihistamines

and leukotrienes in blood

May have antispasmodic and anti-inflammatoryeffects

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Butterbur

Summary of Clinical Studies 2012 American Academy of Neurology guidelines for

episodic migraine prevention1

Review of studies from June 1999-May 2009 to assessefficacy of NSAIDs and CAM for migraine prevention

Of the 284 studies reviewed, 15 studies were wereClass I or Class II

Butterbur was the only nonprescription option that wasgiven Level A classification (established efficacy)

Level B (probably effective)

Fenoprofen, ibuprofen, ketoprofen, naproxen

Magnesium, feverfew, riboflavin

1. Holland S et al. Neurology 2012; 78:1346-1353 .

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Butterbur

Summary of clinical studies Butterbur appears to reduce migraine frequency

May reduce intensity and duration of migraine

May decrease nasal symptoms of allergic rhinitis

Doesnt appear to be beneficial for asthma

Dosing Appears to be beneficial at 75mg twice daily

(Petadolax) for migraine

Appears to be beneficial at 50mg twice daily(Petaforce) or 8mg three-four times daily (Tesalin)

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Butterbur

Major Adverse Effects: Use products that are pyrrolizidine alkaloid free to

avoid risk of hepatotoxic, carcinogenic effects

Generally well tolerated

Avoid in patients with allergy to ragweed

Major Drug Interactions: Substrate of CYP450 3A4

Consider avoiding in combination with anticholinergicmedications

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Probiotics

Live organisms that when ingested, confer atherapeutic or preventative health benefit

Organisms: Bacteria

Lactobacillis species (L. acidophilus, L. rhamnosus, L.bulgaricus, L. reuteri, L. casei)

Bifidobacterium species (B. infantis, B. breve, B.longum, B. lactus)

Yeast Saccharomyces boulardii

Benefits of probiotics are strain specific

Only a few of probiotic products on the marketcontain strains that have been studied in clinicaltrials

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Probiotics

Thought to help reestablish gut flora and prevent thepresence of harmful bacteria

May also stimulate immune system In children may affect development of immune tolerance Likely/Possibly Effective for:

Treatment of rotavirus Treatment and pre vention of antibiotic a ssociated diarrhea

(including C. difficile)

Treatment of acute d iarrhea Reduction in sever ity of symptoms with irritable b owel

syndrome Reduction of atop ic dermatitis in at-risk inf ants Prevention of trave lers diarrhea Treatment of pouch itis Treatment of respira tory infections


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Probiotics Dosing and

Administ rat ion

Available as capsules, powders, and in foodproducts such as yogurt Doses vary depending on specific microorganism Dose for bacteria products measured as Colony

Forming Units (CFUs) Doses range 1-100 billion CFUs

Dose for yeast products measured as milligrams S. boulardii dose ranges from 250-500mg per

day

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Probiotics General Adverse

Effects and Interactions

Generally considered safe and well-tolerated May cause: Flatulence

Mild abdominal discomfort

Intestinal gas

Interactions: Separate antibiotics by 2 hours with bacteria-based

probiotics

Avoid yeast-based probiotics with antifungals

Precautions: Cases of pathologic infections

Avoid in immunocompromised patients

Avoid in patients at high risk for sepsis

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OVERVIEW OF PROBIOTICS

INDICATIONS AND EFFICACY

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Acute Infect ious Diarrhea

Focus has been on treatment of diarrhea bydecreasing duration or decreasing complications

Summary of clinical studies: S. boulardii (Florastor), Lactobacillus GG (Culturelle),

L. reuteri and some mixtures are most beneficial Cochrane review showed probiotics:

Reduced risk of diarrhea at 3 days Decreased duration of illness by 24-30 hours Were effective as adjunct therapy to

rehydration Only modest effects in diarrhea related to children

attending day care centers and nosocomial reasons

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Antibiot ic-Associated Diarrhea

Have been assessed for both prevention andtreatment of antibiotic-associated diarrhea (AAD)

One meta-analysis showed probiotics reduced riskof developing AAD by 52%

Most effective if started within 72 hours of antibiotictreatment

L. rhamnosus GG (Culturelle), L. acidophilus and S.boulardii (Florastor)

Meta-analysis showed significant benefit vs.placebo for treatment and prevention of AAD

L. rhamnosus GG and S. boulardii (Florastor)

Also showed prevention of C. difficile

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Irritable Bowel Syndrome

Probiotics used due to their effects on immunesystem and possibility of alteration to gut flora

Mixed results for this indication Variety of strains and dosages tested

B. infantis (Align) appears to be most effective inreducing symptoms of IBS Abdominal pain, bloating, and difficult defecation

B. animalis (Activia) may be effective at improvingquality of life and symptoms such as bloating Combination product (VSL#3) may reduce bloating

in IBS


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Al ign

Contains bifidobacterium infantis 35624 asBifantis with 1 billion CFUs Used to promote healthy bowel function Studies show that it appears to be helpful

in relieving symptoms of IBS

For children can sprinkle contents into colddrink or food

Avoid in patients who are allergic to soy ormilk

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VSL #3

Specific lactobacillus combination probiotic containing viablelyophilized bacteria species including: Lyophilized Bifidobacterium breve, Bifidobacterium longum,

Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillusplantarum, Lactobacillus paracasei, Lactobacillus bulgaricus,Streptococcus thermophilus

Contains 450 billion CFUs

Used as adjunct treatment in ulcerative colitis, IBS, andmanagement of an ileal pouch

Used to help reduce abdominal pain and bloating

Manufacturer recommends that it be used under supervisionof physician

5858

VSL #3

Dosing varies per condition being treated Age and weight based dosing available for children 3

months and older

Needs to be refrigerated Patients should mix powder with either 4 ounces

water, yogurt, ice cream, applesauce or other coldfood

Manufacturer information states safe for children

5959

Culturelle

Contains Lactobacillus GG 10 billion bacteria percapsule

Marketed to improve digestion and overall immunehealth Likely effective for rotavirus diarrhea and other acute

diarrhea in infants

May be effective for prevention of antibiotic associateddiarrhea

May be effective for atopic dermatitis

Dosing varies per condition For infants and children less than 25 pounds: one

capsule daily

Adverse effects: case report of sepsis in infant

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Florastor and Florastor Kids

Contains Saccharomyces boulardii 250 mg (5billion bacteria) per capsule or packet

Marketed to promote, strengthen and maintainintestinal health

May be effective for: Prevention of:

Antibiotic-associated diarrhea Traveler's diarrhea

Diarrhea in tube-fed patients

Recurrence of C.difficile

Treatment of:

HIV-associated diarrhea

Diarrhea in infants6161

Florastor and Florastor Kids

Dosing: 250-500mg 2-4 times per day Capsules can be opened and contents mixed with food

or juice

Adverse effects: May cause flatulence

Case reports of fungemia in immunocompromised

patients Labeling indicates use for patients > 2 months old

Avoid with antifungal agents


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Patient Case #2

One of your regular patients comes in to the pharmacy andwants to speak with you. He has to fly out tomorrow morning fora business meeting and cant be sick. He tells you that he onlywants to take something natural for his symptoms since thoseproducts are safer. You learn the following:

He is having diarrhea 3 loose stools today and wants totake some to stop it

He tells you that he has not experienced any weight loss Upon assessment, he does not appear to have any signs of

dehydration or any other signs or symptoms

You see on his profile that he filled a prescription foramoxicillin 500mg three times per day a few days ago.

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Which of the following

probiotics would be the best

option?

1.VSL #32.Align3.Culturelle4.Activia

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Additional References

Natural Medicines Comprehensive Database. Available atURL:www.naturaldatabase.com (accessed 2/4/13)

McKenney JM, Sica D. Prescription omega-3 fatty acids for the treatment ofhypertriglyceridemia. AJHP 2007; 64:595-605.

Kris-EthertonPM, Harris WS, Appel LJ. Fish consumption, fish oils, omega-3 fattyacids and cardiovascular disease. Circulation 2002; 106;2747-2757.

Dr. Oz and Green Coffee Project. Available atURL:http://www.doctoroz.com/videos/green-coffee-bean-project

Thomas D, Greer F, Committee on Nutrition. Probiotics and prebiotics inpediatrics. Pediatrics 2010; 126:1271-1231.

Guandalini S. Probiotics for the prevention and treatment of diarrhea. J ClinGastroenterol. 2011; 45(3):S149-S153.

Floch MH, Walker WA, Madsen K, Sanders ME, Macfarlane GT, Flint HJ.Recommendations for probiotic use 2011 update. J. ClinGastroenterol. 2011;45(3):S168-171.

Allen SJ, Martinez EG, Gregorio GV, DansLF. Probiotics for treating acuteinfectious diarrhea. Cochrane Library. 2010. Available at URL:http://summaries.cochrane.org/CD003048/probiotics-for-treating-acute-infectious-diarrhoea

6565


Weston S, Halbert A, Richmond P, Prescott SL. Effects of probiotics on atopicdermatitis: a randomised controlled trial. Arch Dis Child 2005; 90 (9):892-897.

Savino F, PelleE, PalumeriE, OggeroR, MinieroR. Lactobacillus reuteri(American Type Culture Collection Strain 55730) versus simethiconein thetreatment of infantile colic: A prospective randomized study. Pediatrics 2007;119;e124-e130

Quigley EMM. The efficacy of probiotics in IBS. J ClinGastroenterol 2008; 42:S85-S90.

Guandalini S. Probiotics for children with diarrhea an update. J ClinGastroenterol 2008; 42: S53-57.

FlochMH, Walker WA, GuandaliniS, Hibberd P, GorbachS, SurawiczC et al.Recommendations for probiotic use 2008. J Clin Gastroenterol 2008; 42:S104-S108.

Fedorak RN, DielemanLA. Probiotics in the treatment of human inflammatorybowel diseases update 2008. J Clin Gastroenterol 2008; 42: S97-S103.

6666


Hume AL. Lactobacillus and antibiotic-associated diarrhea. Pharmacy TodaySeptember 2007.

Thielman NM, Guerrant RL. Acute infectious diarrhea. NEJM 2004; 350-38-47.

Probiotics. Pharmacists Letter/Prescribers Letter 2006;22:220704.

Canani RB, Cirillo P, TerrinG, CesaranoL, SpagnuoloMI, Vincenzo A et al.Probiotics for treatment of acute diarrhoeain children: randomised trial of fivedifferent preparations. BMJ 2007; 335-340

Kligler B, CohrssenA. Probiotics. Am FamPhysician. 2008; 78:1073-1078.

Vanderfoof JA, Young R. Probiotics in the United States. Clinical Infectious

Diseases 2008; 45:S67-72. NCCAM. Get the facts: An introduction to probiotics. 2008. Available at

URL:http://nccam.nih.gov/health/probiotics/

Sazawal S. HiremathG, Dhingra M, Malik P, Deb S, Black RE. Efficacy ofprobiotics in prevention of acute diarrhea: a meta-analysis of masked, randomised,placebo-controlled trials. Lancet InfecDis 2006; 6(6):374-382.

McFarland LV. Meta-analysis of probiotics for the prevention of antibioticassociated diarrhea and the treatment of Clostridium difficiledisease. Am JGastroenterol 2006; 149(3):367-372.

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VITAMINS AND MINERALS


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Some Thoughts on Vitamins and

Supplements

If you heaped all of the vitamins you need eachday in a pile, that pile would be smaller than theperiod at the end of this sentence. Dr. DavidReuben

The problem is not the lack of vitamins, but theoverconsumption of refined foods that inhibit theirmanufacture and use or destroys them onceconsumed

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Some thoughts on Food as Medicine

The difference in what is called a food and what iscalled a medicine is that foods have milder qualities

When most foods are used therapeutically,concentrated quantities must be taken to achieveresults

Herbs have stronger qualities and flavors and mustbe used in prescribed doses to effect a positivechange

7070

Does Everyone Need to take Vitamins

and Supplements?

Ask why the patient is considering a vitamin orsupplement

Evaluate the diet (vegetarian?)

Evaluate situations and medical conditions thatmay lead to depletion of vitamins and minerals(gastric bypass?)

Evaluate current OTC and prescription medicationsthat may lead to interactions or depletions

7171

Any problems wi th gett ing al l

vitamins and nutrients from

foods?

Dirty Dozen foods apples celery sweet bell peppers peaches strawberries imported nectarines grapes spinach lettuce cucumbers domestic blueberries potatoes green beans kale, collards, and leafy greens

Clean 15 foods onions sweet corn pineapples avocado cabbage sweet peas asparagus mangoes eggplant kiwi domestic cantaloupe sweet potatoes grapefruit watermelon mushrooms

7272

Vitamins, Minerals, Supplements

The Womens Health InitiativeStudy showed there was notany reduction in cardiovasculardisease or cancer risk inpostmenopausal women thattook a MVI (multivitamin) daily

Many products containexcessive amounts of

individual vitamins or areadultered to give the naturalproduct therapeutic benefits

Some products arecontaminated with lead,arsenic, mercury and othertoxins through the planting,harvesting, processing steps

7373

Multivitamins in the News - Data from

the Iowa Women's Health Study

Multivitamins, folic acid, iron, and copper,may be associated with increased totalmortality risk in older women

They also found that, in contrast to thefindings of many previous studies, calcium

was associated with decreased risk

Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR Jr. Dietary supplements andmortality rate in older women: the Iowa Women's Health Study. Arch Intern Med.2011;171:1625-1633.


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Multivitamins and Supplements

When the Iowa Women's Health Study started in the1980s, there was a good theory that antioxidants andsupplements could be beneficial because they provideadditional nutrients.

Most studies have found that there is really no beneficialeffects on risk for cardiovascular disease or cancer, andsome found that some of the supplements could beharmful.

* In the Physicians Health Study II of 14,461 malephysicians in the US, the use of multivitamins over 10years did not reduce cardiovascular events, stroke,myocardial infarction or cardiovascular mortality, but didmodestly reduce the risk of total cancer.

* JAMA. 2012;308(17):1802-1803.* JAMA. 2012;308(18):1916-1917. 7575

Vitamins

7676

Vitamin Deficiencies

Can and do occur

1. Due to substance abuse, poverty, eating disorders,dementia

2. Loss of teeth, difficulty in swallowing3. Decreased sense of taste and smell4. Decreased absorption (gastric by-pass), irritable bowel

syndrome

5. Metabolic requirements of chronic diseases, injury,infection

6. Others

Nutritional Supplements

Should be just that instead of as a replacement

7777

Vitamins

Nutrients that cannot be made in the body insufficient quantities and must be consumed

DRI Dietary Reference Intake EAR estimated average requirement average

daily intake to meet the requirements of 50% ofhealthy individuals

RDA recommended dietary allowance averagedaily intake to meet nutrition requirements for 97-98% of healthy individuals

AI - adequate intake used to determine adequatenutritional amounts when RDA not available

UL upper intake levels maximum daily intake thatshould not cause adverse effects

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Vitamins

The percent DV (%DV indicates the percentage ofthe DV provided in one serving

A food providing 5% of the DV or less per serving isa low source while a food that provides 10-19% ofthe DV is a good source

A food that provides 20% or more of the DV is highin that nutrient

7979

Fat Soluble verses Water SolubleFat Soluble Vitamins Water Soluble Vitamins

A,D,E,K C, B

Soluble in lipids Not stored in the body andexcessive amounts are usuallyeliminated in the urine

Absorbed into the lymphatic system of thesmall intestine. Absorption facilitated by bile

Normal and excessive amounts are storedIn body tissues

Celiac disease, cystic fibrosis, cirrhosis of theliver and short gut syndrome can lead to

deficiencies due to malabsorption

Cholestyramine, orlistat and mineral oil mayalso lead to deficiencies in Vitamins A,D,E,K

International units (IU) are used to describedoses of fat soluble vitamins


14/26


8080

Vitamin A

Fat soluble vitamin Includes the retinoids and carotenoids

Essential for normal growth, normal skeletal muscleformation, tooth development

Needed for proper functioning of the organs,especially the eye

Helps regulate the immune system

May help lymphocytes fight infections moreeffectively

8181

Vitamin A

Found in two forms:1. Preformed Vitamin A (retinol and retinyl ester) from

animal sources - liver, egg yolk,

2. Provitamin A (beta carotene) from plant sources- dark green vegetables, red, orange and deepyellow fruits and vegetables

In healthy adults, 90% of bodys Vitamin A is storedin the liver as retinyl esters

Converted to retinol in the small intestine

http://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/ Accessed12/05/2012

8282

Ways to Measure for Deficiencies

Minimal risk of deficiency in adults

Infants and very young children may be deficientbecause not old enough to have stored enough

Plasma levels

Plasma retinol concentration lower than 0.70micromoles/L or 20 micrograms/dL indicatesVitamin A deficiency

Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A,Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel,

Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press; 2001.

8383

Food Sources of Vitamin A

Food mcg RAE per

serving

IU per serving

Sweet potato 1403 28,058

Beef liver (3 ounces) 6582 22,175

Spinach (1/2 cup boiled) 573 11,458

Carrots (raw) cup 459 9,189

Cantaloupe (1/2 cup) 488 3,743

Peppers, sweet, red (1/2cup)

135 2,706

Mangos (1 whole) 112 2,240

Black-eyed peas (1 cup) 66 1,305

Broccoli (1/2 cup) 60 1,208

8484

Recommended Daily Allowance

RDAs for vitamin A are given as mcg of retinol activityequivalents (RAE) to account for the differentbioactivities of animal, plant and supplemental sourcesof Vitamin A

We convert all dietary sources of vitamin A into retinol Given in mcg of retinol activity equivalents (RAE)

1 mcg of retinol = 12 mcg of beta-carotene

1 mcg of retinol = 24 mcg of alpha-carotene If taking Vitamin A supplements, reported as IU

1 IU retinol = 0.3 mcg RAE

1 IU beta-carotene from supplements = 0.15 mcg

1 IU beta- carotene from food = 0.05 mcg

1 IU alpha-carotene = 0.025 mcg

8585

Source Determines Amounts

An RAE cannot bedirectly converted intoan IU without knowingthe source(s) ofvitamin A

A mixed dietcontaining 900 mcg

RAE providesbetween 3,000 and36,000 IU of vitaminA, depending on thefoods andsupplementsconsumed

RDA Source

900 mcgRAE

3000 IU PreformedVi tA

600 0 IU If b eta-carotene fromsupplements

18,000 IU If beta-

carotene fromfood

36,000 IU If alpha-carotene fromfood


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8686

Recommended Dietary Allowances

(RDA) and Tolerable Upper Levels (UL)

RDA male RDA femal e Tol er able Upper

Levels (UL) forpreformed Vit A

male and female

0-6 months 400 mcg RAE 400 mcg R AE 600 mcg R AE (2000IU)

7-12 months 500 mcg RAE 500 mcg RAE

1-3 years 300 mcg RAE 400 mcg RAE 600 mcg RAE (2000IU)



19-51 + years 900 mcg RAE 700 mcg RAE 3000 mcg RAE(10,000 IU)

RAE = retinol activity equivalents 8787

Causes of Vitamin A Deficiency

Children and pregnant women at greatest risk ofdeficiency

Other conditions that reduce Vitamin A absorption Fat malabsorption

Cancer

TB

Pneumonia, nephritis, UTI

Prostate disease

Neomycin, cholestyramine and orlistat may reduceVitamin A absorption

8888

Symptoms of Vitamin A Deficiency

Night blindness

Loss of appetite

Impaired taste and smell

Impaired balance

Xeropthalmia - Abnormal dryness andthickening of the conjunctiva and cornea

Bitots spot triangular shaped spots on thecornea

http://www.eyeway.org/inform/vitmin.htm

8989

Vitamin A Toxicity and SE

Recommended daily intake: Adult men - 900 mcg/day (3000IU)

Adult women - 700 mcg/day (2330IU)

Adult Tolerable Upper Intake Limit = 3000 mcg/day Toxicity risk is from consuming large amounts from

animal sources or from supplements

Excessive amounts of Vit A have been shown toincrease the risk of bo ne fractures (animalsource preformed)

Increased risk of birth defects, liver abnormalities,reduced bone mineral density that may result inosteoporosis and central nervous system disorders

9090

Vitamin A Toxicity and SE

Toxic symptoms can arise after consuming very largeamounts of vitamin A over a short period of time.(Consuming 25,000 IU/kg at one time or 4000 IU/kgdaily chronically can cause toxicity in adults)

Signs of acute toxicity include:- N/V- Headache- Dizziness- Blurred vision and lack of muscular coordination- Painful joints

The teratogenic effects of-cis-retinoic acid (Accutane)have been well-documented.

9191

Clinical Trials wi th Vitamin A

Supplements

ATBC Study (Alpha-Tocopherol, Beta-CaroteneCancer Prevention Study) and CARET Study(Carotene and Retinol Efficacy Trial) showed thatlarge doses of beta carotene with or without 25,000IU of retinyl palmitate did not prevent lung cancer

AREDS2 (Age Related Eye Disease Study) follow

up study to see if beta carotene combined withother antioxidants and minerals can decreasemacular degeneration

Measles in several studies, giving large doses ofvitamin A (200,000 IU) on 2 consecutive daysreduced mortality from measles

Yang HM, Mao M, Wan C. Vitamin A for treating measles in children. CochraneDatabase Syst Rev 2011;2005.


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9292

B Vitamins

Water soluble B-complex vitamin Vitamin B2 (Riboflavin) - Use may cause

discoloration and a yellow-orange colored urine

Niacinamide does NOT lower TG and LDL levels

9393

Niacin (Nicotinic Acid) Toxicity and SE

Niacin can cause flushing of the skin, headache, N/V.Itching of the skin with symptoms improving over severalweeks

Extended release version MAY cause less flushing, butmay cause more GI side effects and possible harm tothe liver. Avoid in people with GI disorders

Niacin can cause histamine to be released, so monitor inpatients with asthma and allergies

May raise BS levels and lead to hyperuricemia LFTs should be performed at the same frequency as

statins when used at doses to improve cholesterollevels

AIM-HIGH

9494

Flushing verses Non-flushing

Three forms of niacin

1. Nicotinic acid2. Nicotinamide3. Inositol hexaniacinate

Flush free niacin is also known as inositolhexaniacinate

May not have SE of flushing, but may not lower LDLor raise HDL cholesterol

9595

Vitamin C (ascorbic acid)

GENERAL

Water soluble vitamin

Required for making collagen in bones, cartilage,muscle, and blood vessels.

Required for making L-carnitine, and certainneurotransmitters

Antioxidant

Helps the body absorb iron from plant sources

9696

Vitamin C

Only 10% to 20% of adults get the recommendednine servings of fruits and vegetables daily.

RDI for adult males = 90 mg/day and for adultfemales = 75 mg/day

Adult Tolerable Upper Intake Limit = 2000 mg/day

Food sources = green and red peppers, broccoli,spinach, tomatoes, potatoes, citrus fruit,strawberries

9797

Vitamin C and Colds

Evidence to date suggests that regular intakes ofvitamin C at doses of at least 200 mg/day do notreduce the incidence of the common cold in thegeneral population, but such intakes might behelpful in people exposed to extreme physicalexercise or cold environments and those withmarginal vitamin C status, such as the elderly and

chronic smokers. The use of vitamin C supplements might shorten

the duration of the common cold and lessensymptom severity in the general population,possibly due to the anti-histamine effect of high-dose vitamin C .


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9898

Vitamin C Deficiency

Acute vitamin C deficiency leads to scurvy. Signs can appearwithin 1 month of little or no vitamin C intake (below 10mg/day)

Initial symptoms can include fatigue, malaise, andinflammation of the gums

As vitamin C deficiency progresses, collagen synthesisbecomes impaired and connective tissues becomeweakened, causing petechiae, ecchymoses, purpura, jointpain, poor wound healing, hyperkeratosis, and corkscrewhairs

Additional signs of scurvy include depression as well asswollen, bleeding gums and loosening or loss of teeth due totissue and capillary fragility

Iron deficiency anemia can also occur due to increasedbleeding and decreased non-heme iron absorption secondaryto low vitamin C intake

Left untreated, scurvy is fatal

9999

Vitamin C Toxici ty

No real downside to taking a 500-milligram supplement,except that some types may irritate the stomach (2000mg/d) and possibly cause diarrhea (can take a non-acidic, buffered form of the vitamin.

Approximately 70%90% of vitamin C is absorbed atmoderate intakes of 30180 mg/day.

At doses above 1 g/day, absorption falls to less than50% and absorbed, un-metabolized ascorbic acid isexcreted in the urine ..

EXCESSIVE AMOUNTS MAY LEAD TO KIDNEYSTONES

Repeated daily doses of 2000 mg or more will acidify theurine

100100

Vitamin C

INTERACTIONS

May increase the amount of aspirin and NSAIDs inthe blood if taken with Vit C

Others

101101

Vitamin D

According to a 2009 report in the "Archives of InternalMedicine," as much as 77 percent of the Americanpopulation is vitamin D deficient

Cholecalciferol (vitamin D3) naturally occurring form ofVit D

Synthesized in the skin after exposure to sunlight

Ergocalciferol (vitamin D2) used as a food additive

Acts as both a hormone and a vitamin Renal and hepatic dysfunction may lead to Vitamin D

deficiency because of their role in vitamin D metabolismand elimination

102102

Vitamin D

Vitamin D

Promotes calcium absorption in the gut

Maintains adequate serum calcium andphosphate concentrations to enable normalmineralization of bone

Vitamin D is needed for the proper formation ofbone and mineral homeostasis

Involved with parathyroid hormone, phosphate andcalcitonin in the homeostasis of serum calcium

May reduce the risk of heart disease and somecancers

103103

Vitamin D2 versus Vitamin D3

Vitamin D2 Vitamin D3

Vitamin D2 comes from plants When UVB light from the sunstrikes the skin, we synthesizevitamin D3

Vitamin D2 does not bind as well tothe receptors in the human tissuescompared to vitamin D3

Vitamin D3 may be less toxic thanD2

Vitamin D3

is the more potent formof vitamin D


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104104

Vitamin D2 versus Vitamin D3

Vitamin D3 is more stable on the shelf compared toD2, and is more likely to remain active for a longerperiod of time and when exposed to differentconditions (temperature, humidity, and storage).

Vitamin D3 has been the most utilized form ofvitamin D in clinical trials, and there have only beena few clinical trials of vitamin D2 to prevent bonefractures in adults.

Vitamin D3 is more effective at raising andmaintaining the vitamin D blood test ( D2 binds lesstightly to the vitamin D receptors in the body;therefore, D2 does not circulate as long in the body,which means it has a shorter half-life).

105105

Vitamin D Deficiency

From inadequate intake, GI disorders, chronic renalfailure Inadequate sunlight exposure or overuse of sunscreen American Academy of Pediatrics breastfed infants

need 400 IU vit D supplement/day. Once weaned ornon-breast fed infants need 400 IU/day

People with dark skin Patients that have a BMI > 30 or have had gastric

bypass surgery Long term phenytoin therapy - Anti-seizure or

anticonvulsant medications, such as phenobarbital,Dilantin, Mysoline, and Depakote - lower levels ofvitamin D caused by the liver removing an increasedamount of vitamin D from the body

106106


Serum concentration of 25(OH)D is the bestindicator of vitamin D status.

Reflects vitamin D produced from sun exposureand that obtained from food and supplements andhas a fairly long circulating half-life of 15 days.

In the kidney, 25 hydroxy vitamin D is convertedinto the active form of vitamin D

Serum 25(OH)D levels do not indicate the amountof vitamin D stored in body tissues

Screening for Vitamin D deficiency NOTrecommended for everyone

107107


Circulating 1,25(OH)2D is generally not a goodindicator of vitamin D status because it has a shorthalf-life of 15 hours and serum concentrations areclosely regulated by parathyroid hormone, calcium,and phosphate.

Levels of 1,25(OH)2D do not typically decrease untilvitamin D deficiency is severe

When the dose of vitamin D is 150 nmol/L (>60 ng/mL)

109109

Toxicity and SE of Vitamin D

Recommended daily intakes are 600 IU/day for mostadult men and women and 800 IU/day for men andwomen > 70 years old

The upper limit for Vit D is 4000 IU daily If adults are deficient, they can take 50,000 IU once a

week or 6,000 IU daily for 8 weeks until levels are >30 ng/ml

Excessive amounts of Vit D can lead to anorexia,hypercalcemia, kidney stones, renal failure and increasethe risk of some cancers

Excessive amounts may increase the risk of breast,esophageal, prostate and pancreatic cancer, vascularand tissue calcification


19/26


110110

The Finnish Vitamin D Trial (FIND)

A large-scale trial, the Finnish Vitamin D Trial(FIND) will be done to determine whether vitamin Dsupplementation helps in the primary prevention ofcardiovascular and cancer

Studies like the VITamin D and omegA-3 triaL(VITAL) trial in the United States are under way toinvestigate whether vitamin D supplementationreduces the risk for cardiovascular disease orcancer.

111111

Vitamin E (Tocopherol)

Fat soluble vitamin Functions as an anti-oxidant, especially when combinedwith selenium and Vitamin C

Many clinical trials with Vit E have not shown clinicalbenefits in treating chronic conditions such asParkinsons and Alzheimer's

The HOPE and HOPE-TOO trials provide evidence thatmoderately high doses of vitamin E supplements do notreduce the risk of serious cardiovascular events amongmen and women >50 years of age with establishedheart disease or diabetes

Naturally occurring vitamin E exists in eight chemicalforms that have varying levels of biological activity

112112


Serum concentrations of vitamin E (alpha-tocopherol) depend on the liver, which takes up thenutrient after the various forms are absorbed fromthe small intestine.

The liver preferentially re-secretes only alpha-tocopherol via the hepatic alpha-tocopherol transferprotein. The liver metabolizes and excretes theother vitamin E forms .

Blood and cellular concentrations of other forms ofvitamin E are lower than those of alpha-tocopherol

113113


Found in wheat germ, vegetable oils, margarine,nuts, green leafy vegetables

Low-fat diets might provide insufficient amounts ofVitamin E, unless people increase their intakes ofnuts, seeds, fruits, and vegetables

Average diet contains 3-15 mg of Vit E

Deficiency is rare premature, very low birth weightinfants and patients with absorption disorders(cystic fibrosis and biliary disease)

Deficiency associated with symptoms of peripheralneuropathy and muscle weakness

114114


Supplements of vitamin E typically provide only alpha-tocopherol, although "mixed" products containing othertocopherols and even tocotrienols are available.

A given amount of synthetic alpha-tocopherol (listed on labelsas "DL" or "dl") is only half as active as the same amount (byweight in mg) of the natural form (labeled as "D" or "d").

People need approximately 50% more IU of synthetic alphatocopherol from dietary supplements and fortified foods to

obtain the same amount of the nutrient as from the naturalform.

Most vitamin-E-only supplements provide 100 IU of thenutrient, which is higher than the 22IU RDA

Daily doses for health benefits are between 400 and 1000IU/day.

1 mg of alpha-tocopherol vitamin E is = to 1.49 IU

115115

Vitamin E Toxici ty and SE

May increase risk of HF, hemorrhagic stroke, andfetal loss if given to a women with preeclampsia

Recommended intake is 15 mg/day (22 IU) for mostadult men and women

Adult tolerable upper limits 1000 mg/day (1490 IU)

MAY enhance warfarin action if taken in excessiveamounts


20/26


116116

Vitamin E (Drug Interactions)

Plasma levels of vitamin E may be lowered byanticonvulsants (phenobarbital, phenytoin andcarbamazepine).

Vitamin E may decrease the absorption ofdesimpramine, chlorpromazine, propranolol

Vitamin E in large doses (> 1000 mg) may enhance theeffect of anticoagulants (warfarin, heparin, dalteparin,tinzaparin, enoxaparin).

High doses of vitamin E may enhance the effects ofantiplatelet drugs (aspirin, dipyridamole, eptifibatide,clopidogrel, and abciximab).

Orlistat (Xenical) has been shown to reduce theabsorption of certain fat soluble vitamins such as vitaminE.

117117

Minerals

There are more deficiencies in minerals thanvitamins

Minerals needed for assimilation of food, propermetabolism, and offsetting the deterioration ofbones, muscles and other solid structures of thebody

The most assimilated form of minerals comes fromplants

118118

Mineral Composition in the Body

Mineral Percentage in the body

Calcium 39%

Phosphorus 22%

Potassium 5%

Sulfur 4%

Chlorine 3%

Sodium 2%

Magnesium 0.7%

Iron 0.15%

Trace minerals iodine,manganese, copper, nickel,arsenic, bromine, silicon,selenium

Traceamounts

119119

Sources of Minerals f rom FoodsMineral Food sources

Calcium Milk, seaweed, almonds andgreens (avoid spinach and chard)

Iron Kelp, sesame seeds, greens

Magnesium Kelp, almonds, legumes, driedfruit,banana, potato

Phosphorus Seeds, nuts, legumes, grains,dried fruit

Potassium Dried fruit, nuts, avocado, carrots,bananas

Selenium Brazil nuts, whole grains, shellfish

Sodium Kelp, celery, raisins, dried fruit

Zinc Meat, wheat germ

Trace minerals iodine,manganese, copper, nickel,

arsenic, bromine, silicon, selenium

Traceamounts

120120

Different Calcium Salts

Calcium Salt % Elemental Calcium

Calcium gluconate 9.3

Calcium citrate 21

Calcium carbonate 40

121121

Calcium

RDI for adult males and females = 1000 1200mg/day

Adult Tolerable Upper Intake Limit = 2000 2500mg/day

Food sources of calcium = milk, yogurt, cheese,clams, oysters, greens


21/26


122122

Calcium and Spinach

Calcium content of spinach is 115 mg per half cupcooked

Spinach and chard may bind to calcium making itharder to absorb

Because of the interference of oxalic acid, youwould have to eat more than 16 cups of raw ormore than eight cups of cooked spinach to get theamount of calcium available in one cup of yogurt.

123123

Calcium

USES dietarysupplementneeded forvascular contraction,vasodilation, muscle function,nerve transmission

SE/ADR /CAUTIONSCONSTIPATION use withcaution in patients withhypophosphatemia,hypercalcemia

DRUG INTERACTIONSincreased urinary calciumexcretion when used incombination with aluminumantacidsmay decrease peakplasma levels andbioavailability of atenolol..

MEDICATION PROB LEM

Atenolol Decreasedbioavailability andpeak plasmalevels

Iron Decreased GIabsorption

Quinaloneantibiotics

May reducebioavailability of

Thiazide diuretics Hypercalcemiamay occur whenused together

124124

Calcium

Take calcium carbonate products WITH FOOD toincrease absorption

Can take calcium citrate without food, but have totake twice as much citrate as carbonate form

125125

Iron

Type o f iron Percent

elemental

iron

Mg dose Elemental

iron content

in mg

Iron fumarate 33% 325 mg 106 mg

Iron sulfate 20% 325 mg 65 mg

Iron gluconate 12% 325 mg 36 mg

126126

Iron

RDI for adult females 19-50 YO = 18 mg/day, forfemales > 50 YO, 8 mg/day

RDI for adult males 8 mg/day


Full term infants are born with enough iron for 6months, 11 mg/day RDI from 6-12 months

Food sources of iron:

Heme form = liver, meat, seafood

Non-heme form = dark green vegetables, ironfortified foods, beans

127127

Iron Toxicity

Iron overdose is one of the leading causes of death inchildren under age 6

Prenatal vitamins may have 60-100 mg of elementaliron/tablet

Chewable MVI -15-18 mg elemental iron/tabletSigns of GI toxicity seen after 20 mg/kg ingested

Moderate toxicity when elemental iron consumedexceeds 40 mg/kg

Consuming more t han 60 mg/kg can head to d eath

More than 4 episodes of vomiting (especially with blood)may indicate toxic iron consumption

Classified in 5 stages with the 1st stage occurring within6 hours after ingestion

hsc.unm.edu/pharmacy/poison/docs/pdf/Vitamins%20&520Iron.pdf


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128128

Magnesium

Needed for normal bone growth and the properfunction of enzymes, maintenance of muscle andnerve functions and normal heart rhythm andimproves immune system

Cannot correct hypocalcemia or hypokalemiawithout magnesium

RDI for males (31 to > 70 YO) = 420 mg/day RDI for females (31 to > 70 YO) = 320 mg/day Adult Tolerable Upper Intake Limit = 350 mg/day Food sources of magnesium = whole grain cereals,

tofu, nuts, legumes, green vegetablesprocessingfood removes almost all of the magnesium

129129

Magnesium

USES dietary supplement, constipation, soak for muscle achesUnofficial uses to prevent kidney stones, inhibit contractions in

tocolysis (preterm labor), leg cramps, improved pulmonary function,lower BP and BS

Deficiency (causes) - malabsorption, diarrhea, alcoholism, diureticuse

Deficiency (symptoms) CNS stimulation, delirium, convulsions,irritability, loss of appetite, N/V, fatigue, and weakness. Asmagnesium deficiency worsens, numbness, tingling, musclecontractions and cramps (hyperglycemia in people with diabetes)

CAUTIONS use with caution in patients with renal insufficiencySigns of excess magnesium - changes in mental status, nausea,

diarrhea, appetite loss, muscle weakness, extremely low bloodpressure, and irregular heartbeat [

DRUG INTERACTIONS decrease absorption of digoxin

130130

Different Magnesium Salts

Mag ne si um S al t %

MAGNESIUM

Bioava il ab i li ty Use

Magnesiumchloride (hydrous)

12 high Dietary supplement

Magnesiumcitrate(anhydrous)

16.2 high laxative

Magnesiumgluconate(hydrous)

5.4

Magnesiumhydroxide(anhydrous)

41.7

Magnesium oxide(anhydrous)

60.3 low supplement

Magnesiumsulfate (hydrous)

9.9 Soak for muscleaches and laxative

131131

Zinc

Responsible for over 100 enzyme reactions Necessary for growth and development Avoid taking this medication together with foods that are

high in calcium or phosphorus, which can make it harderfor your body to absorb zinc sulfate

Used for boosting the immune system, treating thecommon cold and recurrent ear infections, andpreventing lower respiratory infections. Using zinc as apill or a nose spray doesnt prevent colds. May shortenthe duration of colds by 3-4 days if taken within 24 hoursof onset of cold.

Zinc lozenges used to treat colds usually contains zincgluconate or zinc acetate (3.3 mg of elemental zinc ineach lozenge). One lozenge every 2-4 hours for up to lozenges per day used to treat colds

132132

Zinc

Used to treat malaria and other diseases caused byparasites

RDI for adult males = 11 mg/day and for adultfemales = 8 mg/day


Food sources of zinc = Shellfish, oysters, liver,beef, milk, wheat germ

133133

Zinc TOXICITY AND SE

Zinc is LIKELY SAFE for most adults when taken by mouth inamounts not larger than 40 mg per day. In some people, zinc mightcause nausea, vomiting, diarrhea, metallic taste, kidney and stomachdamage, and other side effects. Using zinc on broken skin maycause burning, stinging, itching, and tingling.

Taking high amounts of zinc is LIKELY UNSAFE. High doses abovethe recommended amounts might cause fever, coughing, stomachpain, fatigue, and many other problems.

Taking more than 100 mg of supplemental zinc daily or takingsupplemental zinc for 10 or more years doubles the risk ofdeveloping prostate cancer. There is also concern that taking largeamounts of a multivitamin plus a separate zinc supplement increasesthe chance of dying from prostate cancer.

Taking 450 mg or more of zinc daily can cause problems with bloodiron. Single doses of 10-30 grams of zinc can be fatal.


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134134

Zinc -TOXICITY AND SE

Zinc nose sprays (Zicam, Cold-Eeze) arePOSSIBLY UNSAFE. These products may causeloss of ability to smell. In June 2009, the US Foodand Drug Administration (FDA) advised consumersnot to use certain zinc-containing nose sprays(Zicam) after receiving over 100 reports of loss ofsmell. The maker of these zinc-containing nosesprays has also received several hundred reports ofloss of smell from people who had used theproducts. Avoid using zinc nose sprays.

135135

Zinc PREGNANCY AND LACTATION

Zinc is LIKELY SAFE for most pregnant andbreast-feeding women when used in therecommended daily amounts (RDA).

Pregnant women over 18 should not take morethan 40 mg of zinc per day; pregnant women age14 to 18 should not take more than 34 mg per day.

Breast-feeding women over 18 should not takemore than 40 mg of zinc per day; breast-feedingwomen age 14 to 18 should not take more than 34mg per day.

136136

Zinc Drug/Supplement Interactions

Anti biot ics (Quino lone antib iot ics)

Zinc might decrease how much antibiotic the body absorbs. Taking zincalong with some antibiotics might decrease the eff ectiveness of someantibiotics. To avoid this interaction, take antibiotics at least 2 hours before or4-6 hours after zinc supplements. Some of these antibiotics that mightinteract with zinc include ciprofloxacin (Cipro), levofloxacin (Levaquin)

Anti biot ics (Tetrac ycli ne ant ibio tic s)

Zinc can attach to tetracyclines in the stomach. This decreases the amount oftetracyclines that can be absorbed. Taking zinc with tetracyclines mightdecrease the effectiveness of tetracyclines. To avoid this interaction, taketetracyclines 2 hours before or 4-6 hours after taking zinc supplements.

Calcium

Calcium supplements might decrease dietary zinc absorption. This usuallydoesn't seem to be much of a problem. However, this interaction can beavoided by taking calcium supplements at bedtime instead of with meals.

137137

How do we advise patients that ask

about dietary supplements?

138138

Selection o f dietary supplements

Ask why the patient is considering a vitamin orsupplement

Evaluate the diet (vegetarian?) Evaluate situations and medical conditions that may

lead to depletion of vitamins and minerals (gastricbypass?)

Known contraindications? Evaluate current OTC and prescription medications that

may lead to interactions or depletions Time release verses regular release Oral versus injection

1. Pharmavite Vitamin Wheel2. RDA/AI, UL lists

139139

Drug Nutrient Depletion Resources

Natural Medicines Comprehensive Database Pharmacist Letter

Natural Standard

Vitamin & Herb University - Pharmavite


24/26


140140

Resources

Company specific websites Nutrition Possible.com (Centrum)

www.vitaminuniversity.com (Pharmavite)

Printed charts

List of USP (Dietary Supplement Verification)verified companies http://www.usp.org/usp-verification-services/usp-verified-dietary-supplements/verified-supplements

141141

Quality

Use and sell brands that you know have consistentdoses of ingredients across batches

Low in toxins

Come from companies that meet GMP

142142

USP Verification Process

Ensures

Quality ingredients are used

Product is consistent across batches as far aspotency and purity (lists any potential allergens)

Product label meets specifications and label claimsthat are valid

Ensures Good Manufacturing Processes (GMPs)are met

143143

USP Verification Process

PROCESS

Expert committee completes an initial review

Manufacturing processes are evaluated

Quality control review is completed

Product samples are tested in a laboratory

USP Verified mark is awarded

Periodic product testing is performed

144144

USP Verified Companies

Banner Pharmacaps Inc. Selected private-label brand supplements

IVC Nutrition Corpo ration Selected private-label brand supplements

International Vitamin Corporation Selected store and private-label brand supplements

Joun Health Inc. Pharmavite LLC

Nature Made brand supplements Nature's Resource brand herbal supplements Selected store and private-label brand supplements

Robinson PharmaInc. Selected private-label brand supplements

Schiff Nutrition Schiff brand supplements Selected store and private-label brand supplements

145145

USP Verified Companies

Perrigo Company of South Carolina Selected private-label brand supplements

Natural Factors Nutritional Products Selected private-label brand supplements

NBTY Inc. Kirkland Signature brand supplements

Northwest Natural Products

Uni-caps, LLC Selected private-label brand supplements

WePackItAll


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146146

Mega doses of vi tamins and

supplements

Doses are usually 50 to 150% of the dietaryreference intake amount

Avoid a product has more than 200% of the dietaryreference intake amount

147147

Vitamin/Supplement/Herb Information

Sources

Natural Standard Consumer Lab (requires paid subscription) Office of Dietary Supplements ([email protected]) Nature Made vitamins (www.naturemade.com) Vitamin Herb University (www.vitaminherbuniversity.com) University of Maryland Medical Center website (http://www.umm.edu/altmed/ ) University of Michigan http://www.med.umich.edu/1libr/aha/umherb01.htm American Botanical Council Pharmacist Letter Natural Medicines Database www.RxFiles.ca (herbal-drug interaction chart) NCCAM - National Institutes of Health, National Center for Complementary and

Alternative Medicine www.nccam.nih.gov USDA National Agriculture Library Dietary Supplements: Resources for

Professionalshttp://www.nal.usda.gov/fnic/pubs/bibs/gen/dietarysupplementsprofessionals.pdf

Memorial Sloan-Kettering Cancer Center About Herbs, Botanicals & OtherProducts

148148

Which of the following regulations

requires manufacturers t o report

serious adverse effects of herbs and

dietary supplements?

A. Dietary Supplement Health andEducation Act of 1994

B. Federal Food Drug andCosmetic Act

C. Dietary Supplement andNonprescription ConsumerProtection Act

D. Kefauver Harris Amendment 149149

A patient wi th dysl ip idemia wants to star t

omega-3 fatty acids. His profil e shows

elevated LDL, elevated trig lycerides and at

goal HDL. Which of the foll owing doses of

omega-3 fatty acids woul d you tell him i s most

effective for him to reach target lipid goals?

A. 1 gram per dayB. 4 grams per dayC. More is betterso he

should take as much ashe can tolerate

D. None of the above,omega-3 fatty acids willnot be beneficial for

this patient

150150

What Vitamin is fat soluble, necessary

for proper eye function and may

increase bone fractures if taken in

excess?

A.Vitamin AB.Vitamin B1

C.Vitamin CD.Vitamin D3

151151

What is a reputable resource for

finding information about the uses,

doses and potential side effects of

herbs, vitamins and supplements?

A.National InquirerB.Natural StandardC.Vitamin KingdomD.Happy Hempster

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Key Points

Use of herbal products and dietary supplements isgrowing in the US; many patients use as adjunct totraditional care

In some cases, it is necessary for patient tosupplement with herbs and dietary supplements

Evidence based information can be found andshould be used

Natural does not = safe

herbs recommendations

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