Transcript Likely Effective - Benton Franklin County Medical Society

Nutritional and Weight Loss Supplements
Galen Goertzen, PharmD
Group Health Cooperative
Disclosures
• No conflicts of interest or commercial affiliations
• Free of commercial bias
• Includes unlabeled uses for ALL discussed natural
medicines
Objectives
• Discuss the process by which dietary supplements
reach the US market and the FDA’s role in that
process
• Provide brief overview of most common dietary
supplements used by adults in the U.S.
• Discuss the evidence for efficacy and safety for the
various dietary and weight loss supplements
• Identify evidence-based natural medicine resources
for clinicians and members.
Background
• Use of herbal products has increased by nearly 400%
during the last decade.
• There appears to be an implicit belief that, because
herbal remedies are natural, they are safe.
• The FDA does not regulate herbs for content and
safety.
• Dietary Supplement and Nonprescription Drug Consumer
Protection Act serious adverse event reporting – effective on
products labeled after December 22, 2007 (enforcement begins
1/1/2010).
Who is doing it?
U.S. CAM Patient Demographics
• 38% of adults
• 41% of adults aged 60-69
• 1 in 9 children
• 42.8% women
• 55.4% of people with higher levels of
education - Masters, doctorate or
professional
• 60% of pregnant and breast-feeding
women
60-70% do NOT disclose this information to their doctors
2007 Statistics on CAM Use in the United States, http://nccam.nih.gov/news/camstats/2007/
What’s the concern?
Not all Dietary Supplements are Created Equal
What’s the concern?
Differences in Regulatory Standards
Drugs vs. Supplements: Different Regulatory Standards
Rx Drugs
Supplements
Proof of Safety
Required
Not required*
Proof of Effectiveness
Required
Not required
Post-marketing Surveillance
Required
Not required**
Good Manufacturing Practices (GMPs)
Pharmaceutical GMPs
Food GMPs***
Disease Treatment Claims
Allowed
Not allowed
* Premarket notification is required for "new dietary ingredients" which have not been previously marketed. However, proof of safety is not required.
** Starting in 2007 dietary supplement manufacturers are required to report adverse event information that they receive to the FDA.
*** Dietary supplement GMPs are in development by the FDA
What’s the concern?
Safety and other concerns
• Toxicity – may be inherently unsafe when orally ingested i.e.
ephedra, aristolochic acid
• Adulterants – contamination, particularly with imported
products – i.e. Man Up Now and Vigor-25 contain sulfoaildenafil
• Dosage variability – active ingredients may vary wildly
between different products – i.e. hoodia
• Risks to special populations – what is effect in pregnancy,
children, kidney disease
• Economic risks – May be considerably more expensive than
FDA approved products on market – Airborne, Red Yeast Rice
vs. lovastatin
What’s the concern?
Drug-Supplement Interactions
•The POTENTIAL for interactions is huge.
•We know that drug-supplement interactions do in FACT occur based on
case reports and some clinical studies.
1. Pharmacokinetic These interactions occur when absorption, distribution,
metabolism, or elimination (ADME) of a drug is altered.
•Calcium: quinolone antibiotics, tetracycline, bisphoshonates, levothyroxine
•St. John’s wort: CYP3A4 substrates
2. Pharmacodynamic interactions can often be predicted based on the
pharmacology of a drug and supplement. These interactions can occur when the
pharmacological effects of two products are additive or oppositional.
•Kava: Hepatotoxic drugs
•Ginkgo: Antiplatelet drugs
What’s the Concern?
Fad ingredients particularly susceptible to adulteration
and fraud
• Products for “Sexual enhancement” - > 80 FDA actions
•Claim to work in minutes or hours or have long-lasting effects up to 24-72
hours
• Weight Loss products - >70 FDA actions
• “Bodybuilding” products - > 80 FDA actions
• Claim to be legal alternative to anabolic steroids
• Watch particularly for products marketed in foreign language or
through mass e-mails
• Are the claims too good to be true???
What’s the concern?
$2.5B Spent, No Alternative Med Cures
•Ten years ago the government set out to test herbal and other alternative
health remedies to find the ones that work.
•No better than PLACEBO in big studies funded by the NIH National Center
for Complementary and Alternative Medicines.
•Echinacea for colds.
•Ginkgo biloba for memory.
•Glucosamine and chondroitin for arthritis.
•Black cohosh for menopausal.
•Saw palmetto for prostate health.
•Shark cartilage for cancer.
•The lone exception: ginger capsules may help chemotherapy nausea.
•Studying herbals is tough because they are not standardized as
prescription drugs are required to be.
http://nccam.nih.gov/
Evidence based information
Complementary & Alternative Medicine Databases
• Natural Medicines Comprehensive Database
• Natural Standard - AAFP recommended resource
• ConsumerLab.com - A Quality "Watchdog" for Herbal and
Dietary Supplements
CAM on PubMed
http://nccam.nih.gov/research/camonpubmed/
Cochrane Database – search in reviews by topic
and select Complementary Medicine Field
http://www.cochrane.org
Natural Medicines Watch™
How to help patients select a natural
supplement
Step #1: Safety Assessment
• Safety Rating: Likely Safe to Unsafe
Step #2: Effectiveness Assessment
• Effective to Likely Ineffective
Bring Safety and Efficacy Together
Developed by Natural Medicines Comprehensive Database
How to help patients select a
natural supplement
Step #3: Product Quality Assessment
Look for the USP-Verified Mark
• USP standards are enforceable by the FDA.
• The mark represents that USP has rigorously tested
and verified the supplement to assure the following:
•
•
•
•
What's on the label is in fact in the bottle.
The supplement does not contain harmful levels of contaminants.
The supplement will break down and release ingredients in the body.
The supplement has been made under good manufacturing practices.
Practice Pearl – National Vitamin Company is USP verified for disintegration and
dissolution standards. They maintain Pharmaceutical Standards of GMP and are in
compliance with Pharmacopeia standards for measuring identity, strength, quality, and
purity of active ingredients.
USP Dietary Supplement
Verification Program
• Comprehensive laboratory testing of supplements
against USP standards
• Thorough manufacturing and quality control document
review
• On-site manufacturing facility audit for compliance
with USP standards and FDA current Good
Manufacturing Practices
• Random off the shelf testing to confirm that products
continue to meet USP standards
What patients are taking
Fish Oil
omega-3 fatty acids eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA)
Adults
Effective
Likely safe when used orally and
appropriately. Doses of 3 grams per day and
less can be safely used by most people.
Hypertriglyceridemia. Fish oil from
supplements or from dietary sources can
reduce triglyceride levels by 20% to 50%
Possibly unsafe in large amounts. Doses
greater than 3 grams per day can inhibit
blood coagulation and potentially increase the
risk of bleeding and might also suppress
immune response.
Lovaza is FDA approved as adjunct to diet
therapy in the treatment of
hypertriglyceridemia at 4g/day – no evidence
of increased effectiveness
Pregnancy and lactation
Likely effective
Likely safe
Cardiovascular disease. Consuming fish oil
from dietary sources (fish), two servings of
fatty fish/week, seems to reduce the risk of
developing cardiovascular disease (primary
prevention)
Children
Possibly safe
Consider recommending in adults
Echinacea
echinacea angustifolia; echinacea pallida; echinacea purpurea
Adults
Possibly Effective
Likely safe when used orally, short-term.
Several formulations of echinacea have
been used safely in trials lasting up to 12
weeks.
Common cold. Taking some echinacea
preparations seems to modestly reduce
symptom severity and duration, possibly by
about 10% to 30%
Pregnancy: possibly safe when used
orally, short-term.
Vaginal candidiasis. Taking echinacea orally in
combination with a topical antifungal cream
seems to be effective for preventing recurrent
vaginal yeast infection.
Lactation: insufficient reliable
information available; avoid using.
Product Concerns
Children
Possibly safe when used orally, shortterm; might increase the risk of rash in
some children.
Echinacea products are frequently mislabeled or
may contain no Echinacea. Echinacea products
have been commonly adulterated. Some have
been contaminated with selenium, arsenic, and
lead.
Don’t recommend this product
Glucosamine SULFATE &
Chondroitin SULFATE
Adults
Likely safe when used orally.
Glucosamine has been used safely in
multiple clinical trials lasting from 4
weeks to 3 years. Chondroitin sulfate
has been used safely in studies lasting
from 2 months to 6 years.
Possibly safe when used IM shortterm.
Glucosamine sulfate in combination
with chondroitin sulfate, shark
cartilage, and camphor appears to be
safe when applied topically on an asneeded basis for up to eight weeks.
Pregnancy and Lactation: Insufficient
reliable information available; avoid
using.
Osteoarthritis
Likely Effective
Clinical trials show that glucosamine sulfate orally
significantly improves symptoms of pain and
functionality compared to placebo in patients with
osteoarthritis of the knee in studies up to 3 years.
Note: There is conflicting evidence about the
effectiveness of glucosamine HCl.
Consider recommending in adults
Possibly effective
Clinical research on the effectiveness of chondroitin
sulfate is inconsistent.
Combination products of glucosamine plus chondroitin
are probably effective, but there is no reliable
evidence that it is better than glucosamine alone.
Don’t recommend these products
L-Methylfolate (Deplin)
• Dietary folate is a mixture of different forms of folate –
converted to L-methylfolate enzymatically
• Compared to folic acid in pregnancy and heart
disease – slightly more bioavailable but with continued
use there is no difference in blood levels
• Safety appears to be equivalent to folic acid – avoid
high dose use in elderly (just like folic acid) due to
possible increased cancer risk
•No need to recommend
Nausea Treatments
Pyridoxine (B6) and Ginger
Adults
Pyridoxine:
Both likely safe when used orally.
ACOG considers pyridoxine a first line option for
N/V of pregnancy - however, it should not be used
long-term or without medical supervision
Pyridoxine is possibly safe in amounts
exceeding the recommended dietary
allowance and possibly unsafe in doses
exceeding 1000 mg daily or total doses of
1000 grams (neuropathy).
Pregnancy:
Pyridoxine is likely safe; but possibly
unsafe when used in excessive doses.
There is some concern that high-dose
maternal pyridoxine can cause neonatal
seizures.
Ginger is possibly safe in pregnancy
Children: Pyridoxine is likely safe
25 mg every 8 hours better than placebo
Lower doses also help for nausea
Doxylamine added when patients don't respond to
pyridoxine alone
Ginger:
250 mg four times daily better than placebo and
comparable to vitamin B6. Takes approximately 3
days to see benefit.
Chemotherapy related nausea: Contradictory
evidence of effectiveness for CINV.
PONV: 1 gram one hour prior to surgery seems to
reduce the incidence of 24-hour postoperative
nausea and vomiting
Consider recommending
Summary of Select Supplements in
Adults*
Consider recommending this product.
Safety/Efficacy
Don't recommend using this product.
Likely Safe
Effective
Fish Oil
Likely
Effective
Co-Enzyme Q10
Ginger
Glucosamine Sulfate
Pyridoxine
Possibly
Effective
Chondroitin Sulfate
Flaxseed
Echinacea
Garlic
Ginkgo
Siberian Ginseng
Insufficient
Evidence
Possibly Safe
Recommend against using this product.
Insufficient
Evidence
Possibly
Unsafe
Likely
Unsafe
Unsafe
American Ginseng
Panax Ginseng
Glucosamine HCl
Possibly
Ineffective
*Listed are the best efficacy and safety ratings for each product, different doses and uses may have different
ratings.
Weight Loss Supplements
• Appetite suppression – hoodia, Fenphen
• Metabolism boosters – ephedrine, bitter
orange, caffeine
•Inhibition of nutrient absorption – orlistat
(Xenical), barley, bean pod
Weight Loss Supplements
• Hoodia – succulent from South Africa –
difficult to find so often substituted with cactus
no evidence that it is effective
•Ephedrine (not ephedra) – similar to PPA –
when combined with caffeine may lead to wt
loss – also ↑risk of psychiatric symptoms,
autonomic hyperactivity and palpitations
•Chromium – small effect if any
Weight Loss Supplements
• Bitter Orange – linked to reports of ischemic stroke
and cardiotoxicity including tachyarrhythmia, cardiac
arrest, syncope, angina, MI, ventricular arrhythmia, and
death in otherwise healthy patients
• Conjugated linoleic acid (CLA) - may increase
lean body mass but not decrease total body weight –
may be associated with insulin resistance
Summary of Select Weight Loss
Supplements in Adults*
Consider recommending this product.
Safety/Efficacy
Don't recommend using this product.
Likely Safe
Possibly Safe
Recommend against using this product.
Insufficient
Evidence
Possibly
Unsafe
Likely
Unsafe
Effective
Likely
Effective
Possibly
Effective
- Blond psyllium (for
orlistat side effects)
- Calcium
- Conjugated
linoleic acid
Insufficient
Evidence
- Barley
- Chromium
- St John’s Wort
- Bean pod
- Chitosan
- Glucomannan
- Guggul
- pyruvate
Possibly
Ineffective
- Guar gum
- Garcinia
Ephedra
- Cha de
bugre
- Hoodia
- Usnea
-5 HTP
- Bitter
orange
Aristolochia
- Inulin
*Listed are the best efficacy and safety ratings for each product, different doses and uses may have different
ratings recreated from Pharmacist’s Letter
HCG diet
• Human Chorionic Gonadotropin given by IM
injection or now sublingually in addition to 500800 calorie diet
• Shown to be no more effective than 500-800
calorie diet by itself
• Promoted by Kevin Trudeau in his book, “The
Weight Loss Cure “They” Don’t Want You to
Know About.”
Patient Friendly Information
Patient Handouts from Natural Medicines Database or
Natural Standard
Fact sheets on dietary supplements from the National
Institutes of Health: http://nccam.nih.gov/
Summary
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As with conventional drugs, careful consideration of the risk
vs. benefit should be done before recommending natural
medicines.
Products without clear benefit and safety should be
avoided.
Products that are likely safe and effective or likely effective
and are high quality (e.g. USP-Verified Mark) are
appropriate to recommend.
Ask your patients specifically about herbal products
Find a good consultation source, whether it is a good
database or a good pharmacist!