Show me the Proof: Evidence-based advice on prescribing select vitamins, herbs and minerals
Objectives
Show me the Proof: Evidence-based
advice on prescribing select vitamins,
herbs and minerals
• Having completed the learning activities,
the participant will be able to:
– Recognize indications and therapeutic
actions of commonly used herb, mineral
and vitamin therapies.
– Identify potential problems with the use of
commonly prescribed herbal, mineral, and
vitamin therapies.
Margaret A. Fitzgerald
DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC
President,
Fitzgerald Health Education Associates, Inc.,
North Andover, MA
Family Nurse Practitioner,
Greater Lawrence (MA) Family Health Center
Editorial Board Member
The Nurse Practitioner Journal,
The Prescribers Letter, American Nurse Today
Member, Pharmacy and Therapeutics Committee
Neighborhood Health Plan, Boston, MA
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Objectives
Show Me the Evidence
(continued)
• Having completed the learning
activities…(cont.)
• Evidence of
the supplements
– Discuss the current evidence on the
use of select herbal, mineral, and
vitamin therapies.
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– Efficacy?
– Safety?
3
All vitamins and botanicals are safe.
Right?
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The Dietary Supplement Health and
Education Act (DSHEA) of 1994
Defined dietary ingredient, containing
=>1 or any combination of the
following substances
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Show me the Proof: Evidence-based advice on prescribing select vitamins, herbs and minerals
The Dietary Supplement Health
and Education Act (DSHEA)
The Dietary Supplement Health
and Education Act (DSHEA)
(continued)
• Defined dietary ingredient,
containing =>1 or any combination
of the following substances
• Defined dietary ingredient…(cont.)
– Dietary substance for use by humans
to supplement the diet by increasing
the total dietary intake (e.g., enzymes
or tissues from organs or glands)
– Concentrate, metabolite, constituent
or extract
– Vitamin
– Mineral
– Herb or other botanical
– Amino acid
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DSHEA Labeling
for Nutritional Supplements
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Challenges with
Dietary Supplements
• Must reflect structure/function claim
• Relatively little study
– Change in, the support of, maintenance, or
function of the body
– Drug-supplement interactions
– Use in special
populations including
children, pregnant/lactating
women, elders
• Not allowed
– "This product will prevent osteoporosis."
• Allowed
– "This product supports proper bone health."
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Oversight of Nutritional
Supplement Manufacturing
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Online Resources
• FDA’s Current Good Manufacturing
Practice (CGMP)
• National Center for Complementary and
Alternative Medicine
– Regulations enforced by US Food and
Drug Administration (FDA)
– “Provide for systems that assure proper
design, monitoring, and control of
manufacturing processes and facilities”
– http://nccam.nih.gov
• Office of Dietary Supplements
– http://dietary-supplements.info.nih.gov
– Source:
http://www.fda.gov/drugs/developmentapprovalprocess/man
ufacturing/ucm169105.htm
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Show me the Proof: Evidence-based advice on prescribing select vitamins, herbs and minerals
Online Resources
(continued)
• Natural Medicines Comprehensive Database
– Part of http://prescribersletter.com
– http://www.NaturalDatabase.com
• For latest information on fraud, recall
– http://www.consumeraffairs.com
“Dr. Oz Grilled In Congress, Admits
Weight Loss Products He Touts
Don't Pass 'Scientific Muster‘”
• “Under pressure from Congress,
celebrity Dr. Mehmet Oz on Tuesday
offered to help ‘drain the swamp’ of
unscrupulous marketers using his name
to peddle so-called miracle pills and
cure-alls to millions of Americans
desperate to lose weight.”
– Source: http://www.huffingtonpost.com/2014/06/17/dr-ozcongress_n_5504209.html
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Judge Orders Kevin Trudeau to Pay
More Than $37 Million for False Claims
About Weight Loss Book
Available at
http://www.ftc.gov/news-events/pressreleases/2009/01/judge-orders-kevin-trudeau-paymore-37-million-false-claims-about
Show Me the Evidence:
Probiotics
“A federal judge has ordered infomercial
marketer Kevin Trudeau to pay more than
$37 million for violating a 2004 stipulated
order by misrepresenting the content of his
book, “The Weight Loss Cure ‘They’ Don’t
Want You to Know About.”
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100+ Years Ago
• Food more
“locally sourced”
• Likely contained
significantly more
bacteria, some
helpful, some
harmful, when
compared to
current times
What are probiotics?
Live microorganisms (usually “healthy”
bacteria or “friendly” yeasts) that have
positive human health benefits when
ingested in adequate quantities
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Show me the Proof: Evidence-based advice on prescribing select vitamins, herbs and minerals
Additional Roles of Normal
Flora in GI Tract
Bacteria in the GI Tract
• Energy production
• Vitamin production, esp.
vitamins K, B12, B6,
niacin, riboflavin
• Enhanced absorption of
calcium, magnesium, iron
• Stimulate immune
maturation
• Helpful bacteria
needed in GI tract
• Illnesses arises when
harmful outnumber
helpful bacteria
•
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What keeps the normal flora
“normal” or healthy?
Protection from Pathogens
• Competitive exclusion yields
crowding out pathogens
• First, avoid using many of the medications
we give to help people!
– Bacteriocins
– Peroxides
– Short chain fatty acids
• Lower pH unfavorable to pathogens
– Clearly, this is often not possible nor advisable.
• Examples
– Antibiotics, cancer chemotherapy, products
that elevate stomach pH, others
• Stimulate immune system to secrete
IgA antibodies
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Davis et al, 1976
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Antibiotic use
Complicated by Diarrhea
Use of Probiotics
to Restore Altered Flora
• Broadly, two types
– Disruption of normal intestinal flora
(antibiotic-associated diarrhea [AAD])
– Overgrowth of the opportunistic
pathogen such as Clostridium difficile
(C. difficile-associated diarrhea [CDAD])
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Show me the Proof: Evidence-based advice on prescribing select vitamins, herbs and minerals
Clinical Presentation of
C. difficile Infection
Antibiotics Implicated in CDAD
• Most commonly
– Fluoroquinolones
– Clindamycin
– Cephalosporins
– Penicillins
• Less common
• Most common
• Rarely
– Tetracyclines
including doxycycline
– Aminoglycosides
– Metronidazole
– Vancomycin
– Macrolides
– TMP/SMX
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C. difficile Diarrhea
– Watery diarrhea with =>10 stools per day
• Spectrum from asymptomatic carrier
state to severe fulminant disease with
toxic megacolon
• Likely related to various host and
pathogen factors
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Normal Sigmoid Colon
• Community-acquired among those with
no known risk factors
– 50% of community-acquired cases have no
exposure to antibiotics in preceding 45 days
• 15 to 30% develop recurrent disease
– Rate of recurrence increases with each
failed treatment to >65% when there are
2+ recurrences
– Source: Diggs and Surawicz, 2009; Dial et al., 2008.
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Oral Probiotics–
General Instructions
Pseudomembranous Colitis
• On an empty stomach
– Likely will derive maximal benefit
• 1-2 hours p oral antibiotic
or antifungal
– Likely best not to have probiotic and
antibiotic or antifungal in stomach at
same time
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Show me the Proof: Evidence-based advice on prescribing select vitamins, herbs and minerals
Oral Probiotics–
General Instructions
(continued)
• Start when antimicrobial initiated
– Optimally prior to use if possible
– Continue probiotic for at least 1-2 weeks
post last antimicrobial dose
Probiotics–
Efficacy for Primary
C. difficile, AAD Prevention
PL Detail-Document, Comparison of Common Probiotic
Products. Pharmacist’s Letter/Prescriber’s Letter. July 2012.
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• Bio-K+
• Florajen 3TM
– Lactobacillus acidophilus, L. casei 12.5
billion (regular strength), 25 billion
(strong), or 50 billion (extra strength)
live bacteria per capsule
– Lactobacillus acidophilus, Bifidobacterium
lactis, B. longum, 15 billion live bacteria
per capsule
• Possibly effective
9
• Possibly effective
– Reducing incidence, duration of AAD and
C. difficile colitis
– Reducing incidence, duration of AAD
and C. difficile colitis
33
Probiotic Use for Additional
Clinical Condition
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Yogurt vs. Supplement
• Usual live culture yogurt
• RepHresh Pro-BTM
– 0.1 and 1 billion cells per 6-8 ounce
(0.18-0.24 L) cup
• Activa® “dose” for GI help, 1-3
containers per day, every day
– A variety of species
• Lactobacillus acidophilus (most
common, often single probiotic),
Bifidus, and Lactobacillus casei
– L. rhamnosus, L. reuteri, 5 billion colonyforming units per capsule, taken orally, 1
capsule per day
• Possibly effective
– Adjunct to oral metronidazole for
treatment of bacterial vaginosis, recurrent
UTI in postmenopausal women
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Avoiding AAD, C. difficile Colitis:
Probiotic Examples
Avoiding AAD, C. difficile Colitis
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Show me the Proof: Evidence-based advice on prescribing select vitamins, herbs and minerals
Patient Counseling
in Probiotic Use
Patient Counseling
in Probiotic Use
(continued)
• Additional warning if
using yogurt
• Refrigeration
– Refer to manufacturer’s recommendation
– Separate from
tetracyclines and
fluoroquinolones by =>2
h due to potential
chelation effect that will
reduce antibiotic efficacy
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• Do not expect
– Overnight “cure”
– Permanent GI colonization
• Keep up with therapy for best results
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Coenzyme Q10
• Ubiquitous substance found in every cell
– Synthesized by the body
– Acts as lipid-soluble electron transporter in
the mitochondrial respiratory chain and
oxidative phosphorylation
Show Me the Evidence:
Coenzyme Q10
• Highest levels
– Heart, liver, kidneys, pancreas
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© 2007 Fitzgerald Health Education Associates, Inc.
Effect of statin use on CoQ10
CoQ10
• Adverse effects
• Potentially reduces coenzyme Q10 levels
– Generally well tolerated
– Primarily at serum, not muscular level
• Potential drug interactions
• Statin-induced myopathy
– Potentially related to mitochondrial dysfunction
– Conflicting reports of helpfulness of CoQ10
supplementation to minimize muscle aches, myopathy
– Observed effect on warfarin, with
occasional modest INR prolongation
– Source:
http://naturaldatabase.therapeuticresearch.com/nd/Search.aspx?
cs=&s=ND&pt=14&sh=2&id=12307&a=al&t=4&df1=Zocor&df2
=Simvastatin
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• Dose
– 50-200 mg/d in 2-3 divided doses
• =>300 mg/d occasionally associated with
hepatic enzyme elevation
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Show me the Proof: Evidence-based advice on prescribing select vitamins, herbs and minerals
Topical Capsaicin
• The evidence
– Effective for
temporary
symptom relief of
pain related to
osteoarthritis and
painful conditions
Show Me the Evidence:
Topical Capsaicin
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Capsicum:
• When used topically
– Binds to skin nociceptors, initially causing
neuronal excitation and heightened
sensitivity and cutaneous vasodilation
– Results in selective stimulation of afferent
C fibers, which act as thermoreceptors and
nociceptors, and release of substance P,
sensory pain-mediating neurotransmitter
45
Capsaicin:
Proposed Mechanism of Action
• Possibly safe
̶ When used topically and appropriately
̶ When used intranasally and appropriately,
short-term, up to 14 days for allergic
rhinitis, cluster headache
– Source:
http://prescribersletter.therapeuticresearch.com/ce/ceNDMono.aspx?on
linece=ART&mono_id=945&view=m
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Capsaicin:
Evidence of Efficacy
• Low back pain
• When used topically (cont.)
– Daily use of capsicum-containing plaster
– Fibromyalgia
̶ Followed by refractory period with
reduced sensitivity
̶ After repeated applications, persistent
desensitization occurs, possibly the
result of substance P depletion and
degeneration of epidermal nerve fibers
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Additional Considerations:
Capsaicin
Proposed Mechanism of Action
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• Cream containing 0.025% of the active
capsicum constituent capsaicin 4 times
daily to tender points for 4 weeks seems
reduced tenderness
47
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Show me the Proof: Evidence-based advice on prescribing select vitamins, herbs and minerals
Capsicum:
Evidence of Efficacy
Capsaicin:
Evidence of Efficacy in Cluster HA
(continued)
• How utilized
• Cluster headache
̶ Intranasal application of capsaicin
0.025% (Zostrix®) during acute
cluster HA attached
̶ Use daily X 7 d decreased symptom
severity over the following week
̶ Ipsilateral nostril application appears
to be more effective than
contralateral application
– Intranasal capsaicin
possibly helpful in
reducing frequency
of episodic or
chronic cluster
headache attacks
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Capsaicin: Adverse Effects
• Primarily consistent with topical
pepper application
FDA Drug Safety Communication:
Rare Cases of Serious Burns with the
Use of Over-the-counter Topical
Muscle and Joint Pain Relievers
– 1 in 10 discontinue due to burning,
skin irritation
• Usually improved with repeated use
– Exacerbation of ACE-inhibitor cough
has been reported in patients using
topical capsaicin and taking
ACE-inhibitors
– Source:
http://naturaldatabase.therapeuticresearch.com/nd/Search.aspx?rn
=4&cs=&s=nd&pt=100&id=945
Source:
http://www.fda.gov/Drugs/DrugSafety/
ucm318858.htm
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Per Recent FDA Warning
Per Recent FDA Warning
(continued)
• “A majority of the second- and third-degree
burns were reported with the use of
products containing menthol as the single
active ingredient or products containing
both menthol and methyl salicylate, where
the concentration of the ingredients was
greater than 3% menthol and 10% methyl
salicylate. Few cases reported using a
• “Many cases occurred following one
application of the OTC topical
muscle and joint pain reliever, with
severe burning or blistering
occurring within 24 hours of the first
application of the product.”
capsaicin-containing product.”
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Show me the Proof: Evidence-based advice on prescribing select vitamins, herbs and minerals
Glucosamine and Chondroitin
• American Association of
Orthopedic Surgeons
– Treatment of osteoarthritis (OA) of
the knee
Show Me the Evidence:
Glucosamine and Chondroitin
• Cannot recommend using glucosamine
and chondroitin for symptomatic
knee OA
• Strength of recommendation=Strong
– Source:
http://www.aaos.org/Research/guidelines/OAKSummary
ofRecommendations.pdf
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Products with Anticoagulation/
Antiplatelet Properties
• The 4 Gs, 3 Fs, L&C, others
Show Me the Evidence:
Preoperative Nutritional
Supplement Use
– Garlic, ginger, ginseng, ginkgo
– Feverfew, fish oil, fenugreek
– Licorice, coenzyme Q10
– Also vitamin E, glucosamine, evening
primrose oil
Areas of concern and need for
discontinuation in elective procedures
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Products with Anticoagulation/
Antiplatelet Properties
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Conclusion
(continued)
• Discontinue 1-2 weeks prior to
elective surgical procedure.
– Source: Nutritional Supplements and Perioperative
Evaluation, available at
one.aao.org/asset.axd?id=f8f8c686-4550-4f18-b8b2924b8daa5e74
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Show me the Proof: Evidence-based advice on prescribing select vitamins, herbs and minerals
Additional Reference
• Update on natural product-drug interactions
– Available at
http://www.medscape.com/viewarticle/429776
End of Presentation
Thank you for your time and attention.
Margaret A. Fitzgerald
DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC
www.fhea.com
email: [email protected]
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All websites listed active at the
time of publication.
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