Assessment of dietary supplement safety: What can we learn from poison control center data?

Suzanne Hendrich, PhDUniversity Professor, Food Science and Human Nutrition, Iowa State University, Ames, IA 50011 shendric@iastate.edu

Outline

•Review of American Association of Poison Control Centers (AAPCC) annual reports▫What/how

•Summary of AAPCC adverse event data 2003-2012▫Vitamins▫Minerals▫Dietary botanicals

•Implications for consumers and for the food & supplement industries

American Association of Poison Control Centers (AAPCC)• 57 Poison Control Centers, 1-800-222-1222• AAPCC’s mission is to advance poison centers in

their public health mission.• Produces annual data reports for public use• https://

aapcc.s3.amazonaws.com/pdfs/annual_reports/2012_NPDS_Annual_Report.pdf

• Reports published in Clinical Toxicology• PCs typically directed by Pharm D or RN with

board certification in applied toxicology• PC calls handled by health professionals with

specific toxicology training

Report data• “…reflects only those cases that are not

duplicates and classified by the regional PC as CLOSED. A case is closed when the PC has determined that no further follow-up/recommendations are required or no further information is available. Exposure cases are followed to obtain the most precise medical outcome possible.” AAPCC Ann Rep 2009

• Fatality review team determines if a death should be listed as contributed to by the substance in question.

Substance Categories Most Frequently Involved in Human Exposures (Top 25) AAPCC Ann Rep 2012Substance (Major Generic Category) All substances % Single-substance exposures % Analgesics 311,347 11.59 202,996 9.99Cosmetics/Personal Care Products 211,314 7.87 204,110 10.04Cleaning Substances (Household) 193,802 7.21 172,905 8.51Sedative/Hypnotics/Antipsychotics 162,634 6.05 62,271 3.06Foreign Bodies/Toys/Miscellaneous 110,070 4.10 107,067 5.27Antidepressants 108,773 4.05 45,371 2.23Cardiovascular Drugs 103,922 3.87 50,012 2.46Antihistamines 96,997 3.61 69,241 3.41Topical Preparations 96,431 3.59 94,276 4.64Pesticides 88,694 3.30 82,916 4.08Alcohols 74,858 2.79 26,964 1.33Vitamins 68,168 2.54 59,028 2.90Cold and Cough Preparations 68,144 2.54 49,547 2.44Bites and Envenomations 64,787 2.41 63,993 3.15Antimicrobials 62,426 2.32 51,750 2.55Stimulants and Street Drugs 61,185 2.28 36,027 1.77Hormones and Hormone Antagonists 59,449 2.21 40,874 2.01Anticonvulsants 51,015 1.90 21,757 1.07Plants 49,374 1.84 46,775 2.30Gastrointestinal Preparations 49,035 1.83 37,626 1.85Chemicals 39,571 1.47 33,784 1.66Dietary Supplements/Herbals 37,729 1.40 30,316 1.49Hydrocarbons 36,356 1.35 34,178 1.68Fumes/Gases/Vapors 32,258 1.20 29,338 1.44Electrolytes and Minerals 31,937 1.19 26,287 1.29

Substances with greatest rate of exposure increase in 2012, AAPCC report

•Vitamins were 5th on the list of top 25 substances with increasing rate of exposure, with an increase of 1849 cases over the previous year

•Dietary botanical supplements were 13th on the list with an increase of 1215 exposure cases in 2012 compared with 2011

Deaths contributed to by vitamins, minerals and botanical supplements, 2003-2012 (AAPCC annual reports)

2003 2004 2005*

2006#

2007 2008 2009 2010 2011

2012

Vitamin 4 3 1 1 0 0 0 0 2 1

Mineral 8 9 13 3 0 3 2 3 2 4

Botanical 13 10 13 2 0 0 1 4 4 2

*2005 Codex Guidelines adopted for vitamin and mineral supplements.#FDA ban on Ephedra upheld by US Appeals Court.

Vitamin exposures reported to PCs

•2006—AAPCC reporting format changes—total single case exposures

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

0

10000

20000

30000

40000

50000

60000

70000

<=5yrs6 to 19 yrs>19 yrstotal

Vitamins: major adverse events

In July of 2005, Codex Alimentarius Commission adopted the Guidelines for Vitamin and Mineral Food Supplements. (from FDA website)

  2003 2004 2005 2006 2007 2008 2009 2010 2011 2012Multi-vitamin w/Fe

10 14 11 0 3 1 1 3 0 1

Other B

16 15 18 0 3 1 1 0 1 0Multi-vitamin adult

9 3 8 2 2 0 1 1 1 3

B6 5 9 10 0 0 0 1 0 0 0C 3 3 2 2 2 0 1 0 0 1Niacin 5 3 12 2 4 2 7 5 4 6A 2 2 1 0 0 0 0 1 0 1D 2 0 0 0 1 0 2 2 0 0total 63 53 73 7 17 8 17 17 9 12

Vitamin supplements--summary•Exposure reports seem to be fairly

constant, with a trend to decrease over the last 4 years. Associated with decreasing exposure reports in children ≤ 5 years of age.

•Deaths and major adverse events (requiring hospitalization) are minimal, perhaps benefitted by Codex Guidelines.

Note Change in reporting format from 2006-present to show single exposures only.

Mineral exposures (2003-2012)2003200420052006200720082009201020112012

0

5000

10000

15000

20000

25000

30000

35000

<=5 yrs6 to 19 yrs>19 yrstotal

Major adverse events—mineral supplements—AAPCC reports

  2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

Ca 12 9 12 1 2 1 2 2 0 0

F 0 0 0 0 0 0 0 0 0 0

Fe 17 15 27 7 8 3 8 8 6 7

Mg 2 5 4 1 3 2 1 1 1 1

K 23 22 16 1 1 4 1 1 0 3

Na 2 5 6 1 4 4 1 1 2 2

Zn 0 2 1 0 1 0 0 0 0 0

other 0 1 0 0 0 0 1 1 1 0

total 62 69 70 14 25 19 18 18 16 16

In July of 2005, Codex Alimentarius Commission adopted the Guidelines for Vitamin and Mineral Food Supplements. (from FDA website)

Deaths contributed to by mineral supplements—AAPCC reports

  2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

Ca 1 0 1 0 0 0 0 0 0 2

F 0 0 0 0 0 0 0 0 0 0

Fe 2 1 3 0 0 0 1 1 0 0

Mg 0 1 2 0 0 0 0 0 1 1

K 3 7 4 0 0 0 0 0 0 0

Na 2 0 2 2 0 3 1 1 1 0

Zn 0 0 0 1 0 0 0 0 0 0

total 8 9 13 3 0 3 2 2 2 4**One death from a multi-botanical/multi-mineral supplement

Mineral supplements--summary•Exposure reports seem to show a slight

downward trend since 2008, due to decreasing exposure reports in children ≤ 5 years of age.

•Codex guidelines may have helped reduce serious adverse events from 2006 on, especially from Ca, Fe and K, the major contributors before.

Note greater proportion of adult: child exposures compared with vitamins or minerals: but recent trends are that for all three classes (vitamins, minerals, dietary supplements), exposures of young children predominate!

20032004

20052006

20072008

20092010

20112012

0

5000

10000

15000

20000

25000

30000

35000

Dietary supplements: exposures reported to Poison Control Centers

<=5 yrs

6 to 19 yrs

>=20 yrs

total

Dietary supplements: major adverse events reported to PCs—2001-2010

FDA published “A Dietary Supplement Labeling Guide” in 2005.

  2003 2004 2005 2006 2007 2008 2009 2010 2011 2012Ma huang 23 26 7 3 1 2 0 0 0 0Multi- +

Ma huang71 51 14 6 3 0 0 1 3 2

Gingko biloba

4 1 1 0 0 0 0 0 0 0Echinacea 3 2 1 0 0 0 0 1 0 0Ginseng 2 0 1 1 0 0 0 0 0 0

Kava kava 2 2 2 1 1 2 1 0 0 0St. John's

wort0 1 1 0 0 0 0 0 0 1

Yohimbe 5 9 3 3 2 2 0 0 2 2unknown 16 10 0 0 0 0 7 11 10 6

total 173 176 111 35 34 38 24 33 45 49

Deaths contributed to by dietary supplements reported to PCs

*FDA ban on Ephedra upheld by US Appeals Court.FDA published “A Dietary Supplement Labeling Guide” in 2005.#In 2012, the other death was from a homeopathic supplement.

  2003 2004 2005 2006*

2007 2008 2009 2010 2011 2012

Ma huang 3 5 1 0 0 0 0 0 0 0Multi- +

Ma huang2 2 0 0 0 0 0 0 0 0

Gingko biloba

0 0 0 0 0 0 0 0 0 0Echinacea 0 0 0 0 0 0 0 0 0 0Ginseng 0 0 0 0 0 0 0 0 1 0

Kava kava 0 0 1 0 0 0 0 0 0 0St. John's

wort0 0 1 0 0 0 0 0 0 0

Yohimbe 2 0 0 0 0 0 0 0 0 1unknown 0 0 0 0 0 0 1 2 2 0

total 13 10 13 2 0 0 1 4 4 2#

Trends for dietary supplements•An abrupt change of increased apparent

safety after 2005 is noted—related to FDA guidance re: supplement labeling?

•Exposures reported especially for children continue to increase—why?

•Major adverse events have continued an increasing trend since a low point in 2009. Complex botanical mixtures account for about 1/3 of these; the addition of energy drinks to this category accounts for ~15% of the cases.

SoyEchinaceaGinseng

GinkgoGarlic

Gluco

sam

ine

St. Jo

hn’s w

ort

Pepp

erm

in

t

Fish oilGinger

Fish oil

Glucos-amine Echi-

naceaFlaxseed

Ginseng

Combi-Herbs

Ginkgo

Chon-droitin

Garlic

Co-Q-10

Comparing vitamins, minerals and dietary supplements: PC exposure reports 2003-201220

0320

0420

0520

0620

0720

0820

0920

1020

1120

120

10000

20000

30000

40000

50000

60000

70000

vitaminsmineralsdietary supplements

Major adverse effects of vitamins, minerals and botanical supplements: PC reports 2003-2012

Vitamin exposures occur in much greater numbers but with similar numbers of adverse effects compared with minerals. Why the steeper drop in adverse events from dietary supplements? Perhaps credit goes to labeling, regulation, and to scientific findings, but ingredient combinations in dietary supplements may be much more of an issue than with vitamins and minerals; recently increasing adverse events with dietary supplements (including energy drinks) bear this out.

20032004

20052006

20072008

20092010

20112012

020406080

100120140160180200

vitaminsmineralsdietary supplements

Conclusions

• These data suggest that the dietary supplement industry is responsive to government action (Codex, FDA, the Ma huang/ephedra ban worked!)

• Nothing could be worse for product sales than serious adverse events and deaths—it is in the industry’s best interests to prevent.

• What more needs to be done?▫Fe, niacin seem to continue to stand out as posing

risks.▫Most adverse events with dietary supplements come

from mixtures, emerging and unknown products—increased consumer education seems warranted.

Another perspective: comparison of dietary supplement toxicity reports with other foodborne toxicants in AAPCC data

•In addition to vitamins, minerals and dietary supplements, AAPCC tracks▫Seafood toxins▫Plant toxins▫Other foodborne toxicants

•How do all of these classes of food components compare?

Seafood toxins—AAPCC data

ToxinMajor Death Major Death Major Death Major Deat

h Major Death Major Death

2007 2007 2008 2008 2009 2009 2010 2010 2011 2011 2012 2012

Ciguatera 4 0 5 0 3 0 5 0 4 1 3 0Clupeo-toxic fish 0 0 0 0 0 0 0 0 0 0 0 0Other seafood poisoning

4 0 1 0 1 0 1 0 0 0 2 0Saxitoxin 2 0 2 0 0 0 1 0 1 1 0 0Scombroidtoxicosis

1 0 2 0 1 0 0 0 1 0 0 0Tetrodo-toxin 1 0 1 1 0 0 1 1 0 0 0 1

Food chemical poisonings—AAPCC data

Major Death Major Death Major DeathMajor Death MajorDeath

2008 2008 2009 2009 2010201

0201

1 2011201

2201

2

Capsicum peppers 0 0 0 0 0 0 1 1 0 0MSG 0 0 1 0 0 0 0 0 0 0

mushrooms 39 4 41 3 23 138 2

35 7

Other adverse reactions to food 7 0 8 0 4 1 9 0 8 0

Plant toxins—adverse effects from AAPCC reports (major illnesses)

Plant toxin 2007 2008 2009 2010 2011 2012

Cyanogenic glucosides 0 1 2 1 1 0

Oxalates 3 2 2 0 1 1

Solanine 0 5 0 0 2 2*Toxalbumins (ricin) 1 2 0 0 1 2

*1 death, the only one reported from 2007-2012 for these major plant toxins.

AAPCC data on food-related toxicities: major adverse events, 2007-12 Substance 2007 2008 2009 2010 2011 2012

Other food toxicants 44 46 50 27 60 43Dietary supplements 34 38 24 33 45 49

Minerals 25 19 18 14 16 16

Vitamins 17 8 17 17 9 12

Seafood toxins 12 11 5 8 6 5

Plant toxins 4 10 4 1 5 4

Total related to food borne toxicants 136 132 118 100 135 129

AAPCC data on food-related toxicities: deaths, 2007-12

Substance 2007 2008 2009 2010 20112012

Other food toxicants 0 4 3 2 4 0Dietary supplements 2 0 0 4 4 2Minerals 0 3 2 3 2 4Vitamins 0 0 0 0 2 1Seafood toxins 0 1 0 1 2 1Plant toxins 0 0 0 0 0 1Total from food borne toxicants 2 8 5 10 14 9

Comparing food-related toxicities 2007-2012, AAPCC data

• Overall, food-associated components pose only minor risks (0-~50 cases/yr in the US), with a relatively constant number of cases over recent history.

• Adoption of industry standards may be continuing to mitigate adverse events from vitamins, minerals and dietary supplements.

• Complex formulations of some dietary supplements may be contributing to recent modest increases in adverse effects from this diverse class of substances.

• Local government and seafood industry surveillance probably contribute to low incidence of toxic effects for these foods.

• The advice “buyer beware”, know what you are ingesting insofar as possible remains an appropriate caution.