Cow Disease and Supplements
Wyn Snow, Managing Editor
a letter to the editor of the New England Journal of Medicine,
Dr. Scott Norton warns that dietary supplements with imported ingredients
from cow tissues could expose Americans to mad cow disease. How
real is this danger, and are any steps being taken to protect public
danger is real
cow disease, or bovine spongiform encephalopathy (BSE), is thought
to be caused by prions -- which are unusually shaped proteins that
cause other normal proteins to "flip" into this same unusual shape.
Heat, ultraviolet light, and ionizing radiation do not affect prions.
Thus, precautions used to prevent the spread of viral, bacterial,
and fungal infections are not effective for BSE.
is one of a group of neurological diseases called transmissible
spongiform encephalopathies (TSEs). Specifically, it is:
by ingesting diseased tissue
because of the sponge-like appearance of infected brain tissue
meaning brain disease
epidemic of BSE in Great Britain may have begun either spontaneously
or through scrapie-infected feed stocks. At the time, cow feed was
enriched with a protein supplement consisting of meat-and-bone-meal
(MBM) made from the remnants of slaughtered cows and/or sheep. Scrapie
is a TSE that occurs in sheep.
BSE began, it became epidemic when MBM from infected cows was fed
to calves. BSE has now claimed the lives of 180,000 cows since it
was first diagnosed in 1986. The epidemic peaked in 1992.
can cross the species barrier to humans
recently, it was thought that TSE diseases like scrapie and BSE
could not cross the species barrier to infect other kinds of animals
or humans. In 1996, British scientists linked BSE to a new variant
of a human TSE: Creutzfeldt-Jakob Disease (CJD). As of February
2001, 98 cases of this new variant CJD (nvCJD) have been suspected
or confirmed in the European Union -- 3 in France, 1 in Ireland,
and the remaining 94 in Britain. It takes about 10 years after ingesting
BSE for symptoms of nvCJD to appear.
mammals other than humans and cows are known to have TSE diseases:
sheep, goats, cats, mink, deer, elk, and mice. The prion-protein
that is believed to cause scrapie, BSE, and CJD is an unusual variant
form of a protein that all mammals make. In the normal form, the
protein is spiral shaped. In the disease form, it is folded into
mixed together in the test tube (and presumably in the body), the
disease form causes the normal form to "flip" from the spiral shape
into folded sheets.
are five varieties of human TSEs. Kuru, called the laughing death
by the Fore people of New Guinea who suffered from the disease,
is transmitted by ritualistic cannibalism. Gertsmann-Straussler-Scheinker
syndrome is an inherited human prion disease. Fatal Familial Insomnia
is caused by a mutation in the human prion protein gene. Creutzfeld-Jakob
Disease (CJD) is predominantly a spontaneous mutation of the human
prion protein, and the new variant CJD (nvCJD) appears to be caused
by ingestion of BSE-contaminated materials.
can be caused either by genetic mutation or transmission of prions
from an infected source, but 85 percent of cases occur sporadically
-- meaning spontaneously: that the normal spiral-shaped molecule
"flips" for no apparent reason into the folded shape. CJD has also
been transmitted by several other means, including contaminated
corneal transplant tissue and hormone extracts such as human growth
hormone and gonadotropin derived from cadavers. Incubation periods
range from 3 to 20 years.
kinds of supplements use ingredients from animals?
than one percent of supplements use mammalian ingredients. Both
the National Nutritional Foods Association (NNFA) and the Council
for Responsible Nutrition (CRN) have reported that only 0.4 percent
of supplement sales contain glandular ingredients.
supplements are either made from plants or synthesized in a laboratory.
A smaller number come from animal sources like shellfish. Supplements
with zero risk of being contaminated with BSE include all vitamins,
all minerals, and all amino acids.
supplements that contain glandular products (including some hormones)
are at risk of contamination with BSE. How can we know if supplements
are free of BSE? The usual method -- testing raw materials or final
products for contamination -- won't work for BSE.
for TSE diseases
of April 2001, the only reliable tests for identifying TSE diseases
are done postmortem by examining brain tissue during autopsies.
These tests cannot determine if blood or a live person or animal
is infected. Also, although special staining procedures can detect
the presence of the abnormal prion protein in tissues such as brain,
these methods do not accurately assess how likely it is that the
material would cause infection.
for TSE disease in living subjects are likely to appear soon. British
expert Dr. Stephen Dealler says, "There is probably already enough
data to produce a blood diagnostic test [for living subjects] plus
a corroborating test that would be needed for human testing. If
the various diagnostic companies and groups share some of their
technology amongst themselves then things would move faster."
such tests are not likely to be an effective method of inspecting
cow tissues used as ingredients for dietary supplements to see if
they are contaminated with BSE prions. To protect public health,
different methods are needed.
the spread of TSE diseases
BSE epidemic in Britain was brought under control by eliminating
ruminant MBM from the feed of cud-chewing animals and by slaughtering
animals that are thought to be infected. In the US, several government
agencies have taken a variety of steps to prevent BSE and nvCJD
from appearing in this country. These agencies include the Department
of Agriculture (USDA), Food and Drug Administration (FDA), Centers
for Disease Control (CDC), and National Institutes for Health (NIH).
Actions and dates undertaken by various agencies include:
importation of live ruminants from all countries having BSE (USDA,
prohibition against importation of live ruminants and most ruminant
products to include all countries in the European Union (USDA,
the brains of US cattle with abnormal neurological behavior to
test for BSE (USDA, ongoing)
the use of most mammal protein in the manufacture of animal feeds
given to ruminant animals (FDA regulation, August 1997)
that animal tissues used in drug products, including vaccines,
should not come from a country with BSE (FDA, several letters
to manufacturers starting in 1992)
blood centers to exclude potential donors who have spent six or
more cumulative months in Britain between 1980 and 1996 from donating
blood (FDA guideline, August 1999)
regular surveillance for any cases of nvCJD (CDC, ongoing review
of death certificate data)
research on BSE, CJD, nvCJD and related neurological diseases
date, these methods appear to have been successful. No cases of
BSE or of nvCJD have been discovered in the US.
concerning supplements, the FDA has recommended that the industry
"take whatever steps necessary to assure themselves and the public
that ingredients do not come from cattle born, raised, or slaughtered
in countries where BSE exists." The FDA sent five letters to dietary
supplement manufacturers between 1992 and 2000 concerning importation
of tissues from cows and sheep.
1995, the FDA also initiated a domestic compliance inspection program
-- as part of their GMP inspection program. Supplement manufacturers
are required to have a procedure for ensuring that animal products
from BSE countries do not get into their products. GMP inspectors
must determine if ingredients from cows are used, and if so, must
discover the country of origin. Import restrictions from the USDA
and FDA have been in place since 1989 and 1992 respectively.
list of countries where BSE has been identified is maintained on
the website of the Office International des Epizooties -- a world
organization for animal health (www.oie.int).
capsules can be either vegetable-based or derived from bones and
hides of beef and pork. Gelatin from animals undergoes rigorous
processing -- including prolonged exposure to highly acidic or alkaline
solutions. Even though gelatin is thought to carry little or no
risk of BSE contamination, in 1997 the FDA added gelatin to the
list of products that should not be imported from countries with
precautions for minimizing potential BSE contamination
National Nutritional Foods Association (NNFA) represents approximately
1000 manufacturers and suppliers of dietary supplements. NNFA and
other supplement trade organizations have cooperated with the FDA
from the outset to prevent the spread of BSE to the US.
from companies has been very good," according to Phil Harvey, PhD,
Director of Science and Quality Assurance for NNFA. "Manufacturers
want to be sure their products are safe, and are taking the appropriate
safeguards. Many are switching from bovine [cows] to porcine [pigs]
sources for glandular ingredients. Also, most manufacturers use
domestic rather than imported sources of glandular ingredients."
emphasizes that there has been no evidence of a link between dietary
supplements and human TSEs, even in Europe -- and says, "This is
a perceived health concern, but not a crisis in any sense. Dietary
supplements are far more processed than food, so the chances are
they are safer than food. The FDA has put up rigorous and effective
safeguards to protect us."
primary goal of NNFA is to educate both the public and manufacturers.
According to Harvey, "Our last issue of NNFA Today [their
newsletter for members] was devoted primarily to BSE, and we have
posted a BSE Guidance document on
our website to assist manufacturers with documentation and record
keeping. We also want to make sure that information for the public
is factual and not sensationalized, and that consumers understand
that glandulars are different from vitamins, minerals, and amino
good manufacturing practices (GMP) inspection process now includes
explicit measures for minimizing any risk of BSE contamination.
To pass this inspection, companies must have rigorous methods of
identifying raw materials and documenting their source.
parts of the cow are most dangerous?
tissues carry different risks of infectivity. Also, methods used
in slaughtering and butchering animals can affect the amount of
infectivity -- as can production methods such as heat sterilization
and chemical treatment used to prepare bovine materials.
following list of highest through smallest risk of infectivity was
gathered from an FDA letter to dietary supplement manufacturers
and other US government documents.
Especially brain tissue and spinal cord, possibly also retina of
Adrenal gland, cerebrospinal fluid, dura mater, ileum, lymph nodes,
pineal gland, pituitary gland, placenta, proximal colon, spleen,
Bone marrow, distal colon, liver, lung, nasal mucosa, pancreas,
sciatic nerve, thymus gland.
Skeletal muscles and milk have never shown any infectivity.
people are concerned about whether a specific supplement might contain
glandular ingredients from cows, NNFA's Harvey recommends that store
personnel and manufacturers be queried directly.
the danger is real that dietary supplements with imported glandular
ingredients can be contaminated with mad cow disease, the risk is
also very small. Import barriers placed by US government agencies
have prevented BSE from spreading to US cattle, and most bovine
ingredients for dietary supplements are of domestic origin. Imported
ingredients come from countries that do not have BSE.
standards provide solution to concerns about contamination
with mad cow disease is one of many quality issues that can be addressed
with comprehensive quality standards. Standards for good manufacturing
practices (GMPs) deal with all aspects of manufacturing procedures:
from raw materials to shipping and storage of final products.
GMP inspection and certification program can assure consumers that
products with NNFA's
GMP seal are free of contamination with mad cow disease.
However, NNFA membership does not include all dietary supplement
manufacturers -- so if a company that is not a member of NNFA follows
BSE-preventive practices, the only way consumers can be confident
of this is to ask manufacturer personnel.
Dietary Supplement Health and Education Act passed in 1994 requires
the FDA to establish GMP standards for dietary supplements. The
FDA presented a proposed GMP regulation in 2000, but publication
of a final rule is currently on hold pending appointment of a new
FDA commissioner by President Bush. Until the final rule is published,
dietary supplements continue to be held to food GMP standards.
government regulation can solve many problems, it also has drawbacks:
It is slow to change in response to new scientific information.
A better solution might be to convene a Quality Congress with representatives
from industry, government, health practitioners, supplement researchers,
the insurance industry and consumers. This Congress would be empowered
to establish and maintain ongoing quality standards, including such
issues as contamination with mad cow disease.
safety could be assured either by requiring all supplement manufacturers
to adhere to these standards (the current plan for FDA GMP standards
under DSHEA) -- or by allowing companies to use a seal on their
labels if they have passed third-party inspection of such GMP standards.
"Mad Cow and Human Prion Disease." About.com website, 18 May 1998.
[Article no longer available on about.com website.]
Dealler. "Who is doing what in diagnostics?" Mad-Cow.org website,
15 February 2001. www.mad-cow.org/00/feb01_last.html.
W. Harvey, PhD, Director of Science and Quality Assurance, National
Nutritional Foods Association. Personal communication, 30 March
Nutritional Foods Association (NNFA), Committee for Product and
Label Integrity. "NNFA BSE Guidance Manual." NNFA website, Adobe
Acrobat document (PDF format), March 2001. www.nnfa.org/services/science/bse.htm.
A. Norton, MD, MPH. "Raw Animal Tissues and Dietary Supplements."
Letter to the editor of the New England Journal of Medicine,
Vol. 343, No. 4, 27 July 2000. www.nejm.org
[available for subscribers only].
International des Epizooties. List of countries with BSE, in English:
Spanish and French versions are also available.
B. Prusiner, MD. (Prusiner is the Nobel Laureate who discovered
prions and postulated them as the cause of CJD, BSE and scrapie.)
"The Prion Diseases." Scientific American, Vol. 272, No.
1, Pages 48-57, January 1995.
Food and Drug Administration. "BSE: Background, Current Concerns,
and U.S. Response." FDA website, 1 March 2001. www.fda.gov/opacom/backgrounders/bse.html.
Food and Drug Administration. "Letter to Reiterate Certain Public
Health and Safety Concerns to Firms Manufacturing or Importing Dietary
Supplements that Contain Specific Bovine Tissues." FDA website,
14 November 2000. vm.cfsan.fda.gov/~dms/dspltr05.html.
Food and Drug Administration. "Questions and Answers on Bovine Spongiform
Encephalopathy." FDA website, 2 January 2001. www.fda.gov/cber/bse/bseqa.htm.
Food and Drug Administration. "Safety of Gelatin and Gelatin By-Products
Reviewed." Letter on FDA website, 24 April 1997. www.fda.gov/bbs/topics/ANSWERS/ANS00793.html.
Food and Drug Administration. "Search result for BSE." FDA website,
2 April 2001. vm.cfsan.fda.gov/cgi-bin/ws.cgi?QUERY=bse&STYPE=OR.