REVIEW
Advising Patients Who Use Dietary Supplements
Bimal H. Ashar, MD, MBA, Anastasia Rowland-Seymour, MD
Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, Md.
ABSTRACT
Public use of dietary supplements is quite prevalent, with an estimated 1 of 5 patients using such substances
in an effort to maintain or promote their health. Despite their popularity, patients and physicians are often
unaware of the limited regulation of these products as well as their potential risks and benefits. Lack of
physician knowledge in these areas has the potential to strain the doctor-patient relationship. In this review,
we present a 6-step approach to advising patients who are considering use of dietary supplements. Our
framework includes a discussion of regulatory issues, efficacy and safety, potential supplement-drug
interactions, and monitoring for adverse events and therapeutic effects.
© 2008 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2008) 121, 91-97
KEYWORDS: Complementary and alternative medicine; Dietary supplements; Herbal medicine
The passage of the Dietary Supplement Health and Education Act (DSHEA) in 1994 significantly changed the
way in which herbs, vitamins, and other supplements are
regulated.1 As a result of its enactment, sales of dietary
supplements have soared. Consumers presently spend in
excess of 23 billion dollars every year on natural products
marketed to maintain or enhance health.2 In 2002, nearly
20% of the population used over-the-counter supplements.3
Dietary supplements are generally regarded by patients
as safe. However, a number of adverse events have been
reported over the past few years from the use of these
natural substances.4 Concern over herb– drug interactions
has also arisen.5,6 Surveys suggest that approximately 16%
of Americans who take prescription medications also ingest
supplements.7 Additionally, patients often do not disclose
their alternative medicine use to their health care providers,8
thus making identification of potential adverse events difficult. It is imperative for clinicians to openly discuss dietary
supplement use with their patients in an effort to prevent
untoward effects and strengthen the provider–patient relationship. Additionally, supplements may provide safe and
effective alternatives to prescription medications (eg, fish
oil for hypertriglyceridemia) or safe options for conditions
for which there are no conventional treatments (eg, echinacea for the common cold). This article reviews the fundamental issues surrounding the use of dietary supplements
Requests for reprints should be addressed to Bimal H. Ashar, MD,
MBA, 601 N. Caroline Street, Room 7143, Baltimore, MD 21287.
E-mail address: [email protected]
0002-9343/$ -see front matter © 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjmed.2007.10.031
and presents an approach to discussing these issues with
patients.
REASONS FOR THE POPULARITY OF DIETARY
SUPPLEMENTS
The reasons for the popularity of supplements are numerous. A general theme underlying a majority of alternative
therapies is their emphasis on natural modes of healing.
Dietary supplements are easily accessible, relatively inexpensive, “natural” substances that are purported to improve
or prevent a number of conditions. Herbs and vitamins are
assumed to be milder and safer than human-derived medications. For many patients, the use of supplements represents an effort to take charge of and be instrumental in their
health care. In some cultures, herbs and “traditional” or
“folklore” medicine are integral aspects of normal everyday
life, and may be the framework within which health in
general is viewed. Some patients may also turn to supplements to fill the void created by the dearth of available
preventive medications, while others see them as a quick,
hassle-free cure to an underlying problem. This “cure” can
potentially be obtained without the need for practitioner
visits, lifestyle changes, or unpleasant procedures. Thus,
patients have exerted more autonomy with regards to their
health care. The distrust of the traditional medical system
that has developed over the recent past has likely served as
an impetus for seeking out such autonomy.9
Direct-to-consumer advertising has significantly impacted supplement sales. Companies have aggressively
92
The American Journal of Medicine, Vol 121, No 2, February 2008
marketed their products to the public in print, on the radio,
asked. Physicians have generally avoided open discussion
on television, and over the Internet. Some of these ads have
about such matters,20,21 possibly due to their lack of knowlbeen shown to contain exaggerated, misleading, or blatantly
edge.19 It is important for physicians to be forthright regarding
10,11
incorrect information.
The Federal Trade Commission,
their level of understanding, but they also should convey a
which oversees advertising, operates under the same basic
sense of interest and willingness to learn about specific herbs,
guidelines for all consumer prodvitamins, and other nutraceuticals.
ucts such that “advertising for any
Inquiring about reasons for
product—including dietary supuse of specific supplements is
CLINICAL SIGNIFICANCE
plements—must be truthful, not
also important. Is there a cultural
12
misleading, and substantiated.”
context that needs to be under● Although about 20% of patients use diWhile the Federal Trade Commisstood regarding the supplement
etary supplements, they often fail to
sion provides guidance and overuse? What are the patient’s beliefs
disclose this to their physicians.
sight, it does not “approve” indiabout their health and how do they
● Because supplement use is potentially
vidual product ads before their
think the supplement will affect
dangerous, physicians should encouruse. It instead relies on advertisetheir health? Is it being used for
ment surveillance for enforcement
treatment of a specific condition/
age disclosure by inquiring directly and
of its guidelines.13 This surveilsymptom? Or is it being used for
nonjudgmentally.
lance has led to millions of dollars
possible preventive purposes? The
● Physicians should learn about supplesignificance of making these disof fines being levied against comment safety, efficacy, and regulation
tinctions revolves around further
panies making unsubstantiated or
and discuss these issues with their
discussions of safety and efficacy.
false claims.14
patients.
For example, there are some, albeit limited, data supporting a pos● These measures will assist the patient in
COMMUNICATING WITH
itive clinical effect of saw palmaking informed decisions and potenPATIENTS
metto on symptoms of prostatic
tially strengthen the doctor-patient
There has been much discussion
hyperplasia.22 There is, however,
relationship.
about shared decision-making and
no current clinical or epidemiopatient autonomy with regard to
logic evidence that saw palmetto
treatment choices. This has beis effective for preventing prostate
come an even greater issue given
cancer.23 Discussing these issues with patients enables them
the pervasiveness of direct-to-consumer advertising. The
to perform a more informed cost-benefit analysis with repromotion of patient autonomy has been shown in some
gards to their supplement use.
instances to improve patient care.15 It is important for physicians to avoid a policy of displaying universal disdain for
Step 2: Evaluate the Supplement
the use of supplements, as this can be detrimental to the
When doctors encounter patients taking or requesting a
physician–patient relationship and preclude patients from
prescription for a medication that they may be unfamiliar
fully disclosing their use of herbs and vitamins. Adler and
with, they often consult texts or other references in order to
Fosket suggested that patients did not disclose their comeducate themselves and potentially benefit their patients.
plementary and alternative medicine use to their physicians
This degree of investigation is not common when physifor a variety of reasons, including anticipating their physicians uncover supplement use, however.24 Complicating
cian’s disinterest, anticipating a negative response from
matters further, dietary supplements are often sold as comtheir physician, or assuming that their physician lacked
16
bination products, known by their trade names rather than
sufficient knowledge to contribute useful information.
their specific active ingredients. Supplements such as CorSurveys have suggested that most physicians have an open
17,18
tislim (Window Rock Enterprises, Brea, CA) and Focusfacattitude toward alternative therapies,
but are limited
tor (Vital Basics, Inc., Portland, ME) have become popular
with regards to their ability to discuss complementary and
among the public, who may be unaware of the herbs and
alternative medicine issues due to an inadequate knowledge
19
vitamins that they are ingesting. Physicians need to be
base. The following 6 steps can assist physicians in enaware of and have access to references that can help sort out
gaging patients in discussions about their supplement use
the composition of these products and help describe any
and enhance the shared decision-making process.
safety and efficacy issues. A number of such references are
currently available (Table 1).
Step 1: Inquire About Supplement Use
Effective physician–patient communication requires uninhibited disclosure by patients as well as thorough inquisition
by physicians. Many patients might not volunteer their
alternative medicine use (including dietary supplements) to
their physicians, but they are willing to engage in discussion if
Step 3: Discuss Regulatory Issues
Surrounding Dietary Supplements
It is imperative that we make our patients savvy consumers. Under DSHEA, supplements are not required to have
Ashar and Rowland-Seymour
Table 1
Advising Patients Who Use Dietary Supplements
93
Potential Sources of Information about Dietary Supplements
Internet
National Center for Complementary and Alternative Medicine
http://nccam.nih.gov/health/supplements.htm
http://nccam.nih.gov/index.htm
http://ods.od.nih.gov/
www.naturaldatabase.com
www.naturalstandard.com
http://www.consumerlab.com/results/index.asp
www.mskcc.org/aboutherbs
http://www.cochranelibrary.com
Office of Dietary Supplements
Natural Medicine Comprehensive Database
Natural Standard
Consumer Labs
Memorial Sloan Kettering Cancer Center Integrative Medicine
Cochrane Library’s field group in CAM website (CD-ROM available also)
Print
Evidence-Based Herbal Medicine. Rotblatt R, Ziment I, Eds. Philadelphia, PA: Hanley & Belfus; 2001
Herb Contraindications & Drug Interactions, 2nd edition. Brinker F. Sandy, OR: Eclectic Medical Publications; 2001
Natural Standard Herb and Supplement Reference: Evidence-Based Clinical Reviews. Ulbrich CE, Basch EM. Philadelphia, PA: Elsevier;
2005
PDR for Herbal Medicines. Greunwald J, Brendler T, Jaenicke C, Eds. Montvale, NJ: Thomson; 2004
Food and Drug Administration (FDA) approval before
their production or distribution. Efficacy and safety studies are unnecessary before product marketing. Dietary
supplements are assumed to be safe unless proven otherwise by the FDA through postmarket surveillance.25 This
is in stark contrast to the regulation of drugs, which
require extensive premarket safety and efficacy data and
FDA approval. Additionally, until recently, regulations to
ensure product content and quality have been lacking.
This has lead to significant variability in the composition
of supposedly similar dietary supplements and a lack of
standardization.26 Cases of dietary supplement adulteration have also been reported,27as was the case with PC
SPES, a product that was initially thought to be a promising for treatment of prostate cancer (PC standing for
“prostate cancer” and SPES being Latin for “hope”) but
was found to be adulterated with diethylstilbestrol (a
synthetic estrogen), warfarin, and indomethacin.28
Unfortunately, the public appears unaware of the lack of
governmental oversight of dietary supplements, and may be
making uninformed choices regarding their use of these
substances.29,30 Many physicians are also unfamiliar with
these regulatory issues.31 The passage of DSHEA was
thought to be an act that would enhance patient autonomy.
Yet, in order for an act to be truly autonomous, a substantial
degree of understanding should be present.32 Physicians
have a responsibility to educate their patients about supplement regulation, not to dissuade their use, but to ensure that
a truly informed choice is being made.
In an effort to address issues of product quality, the FDA
has just issued its final rule establishing Good Manufacturing Practices for all dietary supplement companies.33 The
rule should take effect in June 2008 for large companies.
Smaller companies have been given more time to comply
with the regulations, which will be enforced by random
FDA audits. Good Manufacturing Practices include quarantining herbs, proper identification of herbs based on their
chemical composition, and pharmaceutical grade produc-
tion practices. Until all manufacturers are in compliance,
physicians should tell their patients who are interested in
supplements to look for the symbols GMP (Good Manufacturing Practices), NSF (National Safety Foundation), or
USP (United States Pharmacopeia).
Step 4: Discuss the Available Safety and
Efficacy Data
There are only limited data on the efficacy and safety of
many of the dietary supplements currently available. Most
clinical trials have been small, nonrandomized, or unblinded. Recently, some well-designed trials have been published that have given physicians some cogent data to discuss with their patients. Additionally, a number of
systematic reviews have been published on a variety of
supplements. As a complement to the resources listed in
Table 1, physicians can find easily accessible information
on a number of commonly used supplements by searching
medical databases such as Medline and Cinahl.
In addition to side effects that can occur with the use
of dietary supplements, physicians need to be aware of
potential supplement-drug interactions. For example, St.
John’s wort (Hypericum perforatum) has been shown to
potentially decrease the levels of a number of commonly
used drugs, including protease inhibitors,34 warfarin,35
and some hydroxymethylglutaryl-coenzyme A reductase
inhibitors (statins).36 Table 2 lists potential uses, efficacy, side effects, and drug interactions of a few popular
supplements.
Given inherent time constraints, physicians’ lack of
knowledge of supplements, and limited definitive data regarding interactions, it is virtually impossible for physicians
to be aware of all possible adverse reactions that may result
from combining herbs and drugs. However, it is important
for clinicians to be aware of available resources that can assist
in protecting patients from potential untoward effects. In addition to the print and online references listed in Table 1,
94
The American Journal of Medicine, Vol 121, No 2, February 2008
Table 2
Commonly Used Dietary Supplements
Supplement
Common Use
Efficacy
Bitter orange (Citrus
aurantium)
Weight loss
No data to support
effectiveness37
Black cohosh (Actaea
racemosa)
Coenzyme Q10
Cranberry (Vaccinium
macrocarpon)
Echinacea (E. purpurea,
E. pallida, E.
angustifolia)
Ginkgo biloba
Ginseng (Panax spp;
Asian ginseng, Korean
ginseng, American
ginseng)
Glucosamine and
chondroitin
Kava kava (Piper
methysticum)
St. John’s wort
(Hypericum perforatum)
Adverse Effects
Potential Drug Interactions
Case reports of
Avoid use with other stimulants
myocardial
due to theoretical risk of
infarction,38 stroke,39
cardiovascular toxicity
and syncope40
Menopausal
Some short-term (⬍12 weeks) Mild gastrointestinal
None known
symptoms
studies have suggested a
symptoms; case
benefit,41 but the most
reports of hepatitis
and fulminant hepatic
recent 1-year study did
failure43
not42
Data inconclusive for
Heart failure,
Generally well tolerated May decrease the INR in
treatment or prevention of
hypertension,
patients on warfarin46
cardiovascular disease;44
angina,
Parkinson
early data promising for
disease
slowing the progression of
Parkinson disease in high
doses45
Urinary tract
May have a role in preventing Generally well tolerated May increase the INR in
infections
UTIs47; no evidence to
patients on warfarin49
(UTI)
support its use for
treatment of UTI48
Upper respiratory Variations in types of extracts Generally well tolerated; Avoid in patients taking
immunosuppressants51
infections
studied and conflicting
hypersensitivity
results make conclusions
reactions have been
regarding efficacy difficult50
reported
Dementia,
Some data suggest modest
Case reports of
Avoid in patients using
claudication,
improvement in cognitive
spontaneous
anticoagulants due to
tinnitus
performance in patients
bleeding53 and
possible increased risk of
with dementia52
bleeding
seizures54
Diabetes, fatigue Insufficient evidence for its
Generally well tolerated; May decrease INR in patients
use at this time55,56
case reports of
on warfarin57
hypertension,
insomnia, vomiting,
headache, vaginal
bleeding, Stevens–
Johnson syndrome,
and mastalgia51
Osteoarthritis
May be beneficial but effect
Generally well tolerated None known
may be dependent on
preparation58
Avoid use with anxiolytics or
Anxiety
Superior to placebo for short- Sedation, rash; liver
toxicity and fulminant
alcohol due to risk of excess
term treatment of anxiety59
hepatic failure have
sedation
been reported60
Depression
Conflicting study results61
Can cause irritability,
Avoid use with SSRIs due to
insomnia, dizziness
risk of serotonin syndrome;
decreases levels of a number
of drugs (see text)
INR ⫽ international normalized ratio; SSRIs ⫽ selective serotonin reuptake inhibitors.
physicians can take advantage of the expertise of the clinical
pharmacists at their hospitals or in the community. Pharmacists often have access to databases that can quickly crossreference drugs and supplements to assess for interactions.
In order to use this service at local pharmacies, it is important for physicians to advise their patients to disclose their
supplement use to their pharmacist.
Step 5: Compare Risk/Benefit of Use to
Available Conventional Therapies
Patients often choose to use dietary supplements over prescription or nonprescription medications due to their awareness of potential adverse effects from medications. They
may not be aware of such effects from the use of a specific
Ashar and Rowland-Seymour
Advising Patients Who Use Dietary Supplements
supplement. Physicians should discuss the available conventional options and compare them to the benefits and risks
of supplement use. Two examples highlight such an
approach:
Example 1: A 46-year-old woman with obesity, hypertension, and diabetes presents with concerns about her weight.
She states that she has been exercising 5 days per week and
has been fairly strict with her diet but has not been able to
lose more than 5 pounds over the last 6 months. Her thyroid
function is normal. She wants to start taking a supplement
she found on the Internet that advertised that it was “clinically proven” to cause weight loss. By looking at the advertisement, you discover that the probable active ingredient in the supplement is bitter orange.
Although it may be easy to just say to the patient that you
do not believe in weight loss supplements, this approach
may be deleterious to the physician–patient relationship.
After a discussion about the regulatory issues surrounding
supplements, you can report that there is currently no evidence that the supplement is effective and that there have
been reports of serious side effects from the active ingredient in the supplement. As an alternative (if you are comfortable recommending medications for obesity), you may
wish to discuss the efficacy data for a medication such as
orlistat and its potential side effects and cost. This will
provide the patient with considerably more information regarding choices for treatment of her obesity.
Example 2: A 72-year-old gentleman with a history of
recent gastrointestinal bleeding due to peptic ulcer disease
presents to discuss treatment options for his osteoarthritis,
which predominantly affects his knees. He was told to avoid
aspirin and ibuprofen after his discharge and he notes that
acetaminophen does not give him relief. He wants to discuss
using a glucosamine preparation.
It is much more difficult in this case to recommend
conventional therapies. You want to avoid nonsteroidal antiinflammatory medications given his recent bleeding episode. You could start him on a narcotic medication but that
can cause significant toxicity as well. Despite limited evidence of efficacy, it may be reasonable to agree with his use
of glucosamine sulfate, given its safety profile, and follow
his symptoms. Again, you should discuss supplement regulation and the fact that not all glucosamine products are
equivalent. You may even wish to recommend a specific
preparation, given that a number of the positive studies were
done on preparations manufactured by one company (Rotta
Pharmaceuticals, Wall, NJ).58
Step 6: Monitor for Adverse Events and
Therapeutic Response
Although most dietary supplements may be safe, adverse
events and drug-supplement interactions can occur (Table
2). It is important for physicians to monitor for such occurrences and report any suspected cases of significant toxicity
to the FDA. This can be done by accessing the FDA Med-
95
Watch system.62 Reports can be filed online or by mail, fax,
or phone (1-800-FDA-1088). Definitive proof of the toxicity of a supplement is not required before filing a report.
Rechallenge to prove causation is not recommended.
In addition to monitoring for safety, physicians should
also monitor for response. Readdressing treatment after a
number of weeks of therapy is commonplace for conventional medications and should also occur with dietary supplements. For example, a 67-year-old woman presents for
follow-up 12 weeks after starting on a glucosamine preparation for her pain from osteoarthritis of the knee. She notes
no symptomatic relief or functional improvement. Even
though there is some evidence for a disease-modifying benefit from glucosamine,58,63,64 most positive studies used
pain and function as their primary outcome, and most subjects who saw benefit responded within 3 months.58 This
should be discussed with the patient, so that she can make
a decision whether to continue to spend money on the same
supplement, spend money on a different brand, or abandon
its use altogether.
CONCLUSION
The passage of DSHEA has given the public access to a
plethora of products marketed to promote or maintain their
health. It has also resulted in a communication gap between
physicians and patients. Even today, most physicians-intraining have little exposure to dietary supplements and are
ill-equipped to deal with such issues. By following a systematic process, which requires continuing education, physicians can become more comfortable discussing use of
these products and bridge the gap that currently exists.
ACKNOWLEDGMENTS
We thank Tieraona Low Dog, MD for her review of the
manuscript.
References
1. Dietary Supplement Health and Education Act of 1994. Public Law
103-417. Available at: http://www.fda.gov/opacom/laws/dshea.html.
Accessed September 27, 2006.
2. NIH State-of-the-Science Conference Statement on Multivitamin/Mineral Supplements and Chronic Disease Prevention. NIH Consens State
Sci Statements. 2006;23:1-30.
3. Barnes PM, Powell-Griner E, McFann K, Nahin RL. Complementary
and alternative medicine use among adults: United States, 2002. Adv
Data 2004;(343):1-19. Available at: http://www.cdc.gov/nchs/data/ad/
ad343.pdf. Accessed October 8, 2006.
4. Palmer ME, Haller C, McKinney PE, et al. Adverse events associated
with dietary supplements: an observational study. Lancet. 2003;361:
101-106.
5. Hu Z, Yang X, Ho PC, et al. Herb-drug interactions: a literature
review. Drugs. 2005;65:1239-1282.
6. Fugh-Berman A. Herb-drug interactions. Lancet. 2000;355:134-138.
7. Kaufman DW, Kelly JP, Rosenberg L, et al. Recent patterns of medication use in the ambulatory adult population of the United States: the
Slone survey. JAMA. 2002;287:337-344.
8. Robinson A, McGrail MR. Disclosure of CAM use to medical practitioners: a review of qualitative and quantitative studies. Complement
Ther Med. 2004;12:90-98.
96
The American Journal of Medicine, Vol 121, No 2, February 2008
9. Armstrong K, Rose A, Peters N, et al. Distrust of the health care
system and self-reported health in the United States. J Gen Intern Med.
2006;21:292-297.
10. Ashar BH, Miller RG, Getz KJ, Pichard CP. A critical evaluation of
Internet marketing of products that contain ephedra. Mayo Clin Proc.
2003;78:944-946.
11. Morris CA, Avorn J. Internet marketing of herbal products. JAMA.
2003;290:1505-1509.
12. The Federal Trade Commission. Dietary supplements: an advertising
guide for industry. Available at: http://www.ftc.gov/bcp/conline/pubs/
buspubs/dietsupp.htm. Accessed October 8, 2006.
13. The Federal Trade Commission. FTC testifies on the marketing of
dietary supplements. Available at: http://www.ftc.gov/opa/2003/10/
dietarysupptest.htm. Accessed October 8, 2006.
14. The Regulation of Dietary Supplements. Prepared statement of the
Federal Trade Commission. Available at: http://www.ftc.gov/os/2006/
03/P064502CommissionTestimonyConcerningtheRegulationofDietary
Supplements.pdf. Accessed January 2, 2007.
15. Mandelblatt J, Kreling B, Figeuriedo M, Feng S. What is the impact of
shared decision making on treatment and outcomes for older women
with breast cancer? J Clin Oncol. 2006;24(30):4908-4913.
16. Adler SR, Fosket JR. Disclosing complementary and alternative medicine use in the medical encounter: a qualitative study in women with
breast cancer. J Fam Pract. 1999;48:453-458.
17. Crock RD, Jarjoura D, Polen A, Rutecki GW. Confronting the communication gap between conventional and alternative medicine: A
survey of physicians’ attitudes. Altern Ther Health Med. 1999;5:61-66.
18. Astin JA, Marie A, Pelletier KR, et al. A review of the incorporation
of complementary and alternative medicine by mainstream physicians.
Arch Intern Med. 1998;158:2303-2310.
19. Corbin Winslow L, Shapiro H. Physicians want education about complementary and alternative medicine to enhance communication with
their patients. Arch Intern Med. 2002;162(10):1176-1181.
20. Wynia MK, Eisenberg DM, Wilson IB. Physician-patient communication about complementary and alternative medical therapies: a survey of physicians caring for patients with human immunodeficiency
virus infection. J Altern Complement Med. 1999;5:447-456.
21. Roberts CS, Baker F, Hann D, et al. Patient-physician communication
regarding use of complementary therapies during cancer treatment.
J Psychosoc Oncol. 2005;23:35-60.
22. Alvins AL, Bent S. Saw palmetto and lower urinary tract symptoms:
what is the latest evidence? Curr Urol Rep. 2006;7:260-265.
23. Bonnar-Pizzorno RM, Littman AJ, Kestin M, White E. Saw palmetto
supplement use and prostate cancer risk. Nutr Cancer. 2006;55:21-27.
24. Silverstein DD, Spiegel AD. Are physicians aware of the risks of
alternative medicine? J Community Health. 2001;26:159-174.
25. U.S. Food and Drug Administration. Overview of dietary supplements.
Available at: http://www.cfsan.fda.gov/⬃dms/supplmnt.html. Accessed September 27, 2006.
26. Gilroy CM, Steiner JF, Byers T, et al. Echinacea and truth in labeling.
Arch Intern Med. 2003;163:699-704.
27. Cole MR, Fetrow CW. Adulteration of dietary supplements. Am J
Health Syst Pharm. 2003;60:1576-1580.
28. US National Institutes of Health. National Cancer Institute. Questions
and answers about PC-SPES. Available at: http://www.cancer.gov/
cancertopics/pdq/cam/pc-spes/Patient/Page2#Section_5. Accessed December 27, 2007.
29. Blendon RJ, DesRoches CM, Benson JM, et al. Americans views on
the use and regulation of dietary supplements. Arch Intern Med.
2001;161:805-810.
30. Ashar BH, Miller RG, Pichard CP, et al. Patients’ understanding of
the regulation of dietary supplements. J Community Health. 2008;33:
22-30.
31. Ashar BH, Rice TN, Sisson SD. Physicians’ understanding of the
regulation of dietary supplements. Arch Intern Med. 2007;167:966969.
32. Beauchamp TL, Childress JF. Principles of Biomedical Ethics. New
York, NY: Oxford University Press; 1994.
33. U.S. Food and Drug Administration. Dietary supplement current good
manufacturing practices (CGMPs) and interim final rule (IFR) facts
2007. Available at: http://www.cfsan.fda.gov/⬃dms/dscgmps6.html.
Accessed July 8, 2007.
34. Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations
and St John’s wort. Lancet. 2000;355:547-548.
35. Yue QY, Bergquist C, Gerden B. Safety of St John’s wort (Hypericum
perforatum). Lancet. 2000;355:576-577.
36. Sugimoto K, Ohmori M, Tsuruoka S, et al. Different effects of St
John’s wort on the pharmacokinetics of simvastatin and pravastatin.
Clin Pharmacol Ther. 2001;70:518-524.
37. Bent S, Padula A, Neuhaus J. Safety and efficacy of citrus aurantium
for weight loss. Am J Cardiol. 2004;94:1359-1361.
38. Nykamp DL, Fackih MN, Compton AL. Possible association of acute
lateral-wall myocardial infarction and bitter orange supplement. Ann
Pharmacother. 2004;38:812-816.
39. Bouchard NC, Howland MA, Greller HA, et al. Ischemic stroke
associated with use of an ephedra-free dietary supplement containing
synephrine. Mayo Clin Proc. 2005;80:541-545.
40. Nasir JM, Durning SJ, Ferguson M, et al. Exercise-induced syncope
associated with QT prolongation and ephedra-free Xenadrine. Mayo
Clin Proc. 2004;79:1059-1062.
41. Low Dog T. Menopause: a review of botanical dietary supplements.
Am J Med. 2005;118(Suppl 12B):98-108.
42. Newton KM, Reed SD, LaCroix AZ, et al. Treatment of vasomotor
symptoms of menopause with black cohosh, multibotanicals, soy,
hormone therapy, or placebo: a randomized trial. Ann Intern Med.
2006;145:869-879.
43. Lynch CR, Folkers ME, Hutson WR. Fulminant hepatic failure associated with the use of black cohosh: a case report. Liver Transpl.
2006;12:989-992.
44. Shekelle P, Morton SC, Hardy M. Effect of supplemental antioxidants
vitamin C, vitamin E, and coenzyme Q10 for the prevention and
treatment of cardiovascular disease. Evid Rep Technol Assess (Summ).
2003;(83):1-3.
45. Weber CA, Ernst ME. Antioxidants, supplements, and Parkinson’s
disease. Ann Pharmacother. 2006;40:935-938.
46. Heck AM, DeWitt BA, Lukes AL. Potential interactions between
alternative therapies and warfarin. Am J Health Syst Pharm. 2000;57:
1221-1227.
47. Jepson RG, Mihaljevic L, Craig J. Cranberries for preventing urinary
tract infections. Cochrane Database Syst Rev. 2004;(2):CD001321.
48. Jepson RG, Mihaljevic L, Craig J. Cranberries for treating urinary tract
infections. Cochrane Database Syst Rev. 1998;(2):CD001322.
49. Grant P. Warfarin and cranberry juice: an interaction? J Heart Valve
Dis. 2004;13:25-26.
50. Linde K, Barrett B, Wölkart K, et al. Echinacea for preventing and
treating the common cold. Cochrane Database Syst Rev. 2006;(1):
CD000530.
51. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med.
1998;158:2200-2211.
52. Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and
dementia. Cochrane Database Syst Rev. 2002;(4):CD003120.
53. Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding
associated with ginkgo biloba: a case report and systematic review of
the literature. J Gen Intern Med. 2005;20:657-661.
54. Gregory PJ. Seizure associated with Ginkgo biloba? Ann Intern Med.
2001;134:344.
55. Vogler BK, Pittler MH, Ernst E. The efficacy of ginseng: a systematic
review of randomized clinical trials. Eur J Clin Pharmacol. 1999;55:
567.
56. Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS. Systematic review
of herbs and dietary supplements for glycemic control in diabetes.
Diabetes Care. 2003;26:1277-1294.
57. Yuan CS Wei G, Dey L, et al. American ginseng reduces warfarin’s
effect in healthy patients: a randomized controlled trial. Ann Intern
Med. 2004;141:23.
Ashar and Rowland-Seymour
Advising Patients Who Use Dietary Supplements
58. Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2005;(2):
CD002946.
59. Pittler MH, Ernst E. Kava extract versus placebo for treating anxiety.
Cochrane Database Syst Rev. 2003;(1):CD003383.
60. Clouatre DL. Kava kava: examining new reports of toxicity. Toxicol
Lett. 2004;150:85-96.
61. Linde K, Mulrow CD, Berner M, Egger M. St John’s wort for depression. Cochrane Database Syst Rev. 2005;(3):CD000448.
97
62. U.S. Food and Drug Administration MedWatch System. Available at:
http://www.fda.gov/medwatch/index.html. Accessed October 2, 2007.
63. Pavelka K, Gatterova J, Olejarova M, et al. Glucosamine sulfate use
and delay of progression of knee osteoarthritis. A 3-year, randomized,
placebo-controlled, double-blind study. Arch Intern Med. 2002;162:
2113-2123.
64. Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of
glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001;357:251-256.