Office of Dietary Supplements at NIH - Meeting the Needs of a Modern
Wyn Snow, Managing Editor
more than 400,000 published articles of research on dietary supplements,
a reasonable person might wonder, "Why do we need more?"
Paul Coates, director of the federal Office of Dietary Supplements
(ODS), replies: "There is a lot of variability in the quality of
that research -- just as is true of the literature in many fields.
Also, research done as part of a traditional healing system with
centuries of experience is appropriate to that use and context.
However, that same research may not be sufficient to support claims
of effectiveness for a capsule or pill now being marketed for a
purpose that wasn't intended in traditional use."
literature review improves present knowledge and shapes future research
came to the ODS in October 1999 with an agenda of his own. He says,
"We need a systematic approach to evaluating literature used to
support claims of effectiveness and safety."
agrees. This year's Congressional appropriation encourages ODS --
in consultation with the National Center for Complementary and Alternative
Medicine (NCCAM), the Agency for Healthcare Research and Quality
(AHRQ), and the Food and Drug Administration (FDA) -- "to review
the current scientific evidence on the safety and efficacy of dietary
supplements now on the market, which could then form a basis for
further research, education of practitioners and consumers, and
whether further regulatory requirements are necessary."
ODS has embarked on creating a systematic review process. The 2001
budget includes funds to initiate a plan, and they are reaching
out to their partner federal agencies to begin this activity. Coates
believes the review process will fulfill two central ODS obligations:
it will provide solid information to consumers and will help shape
the research agendas necessary to support claims of efficacy and
history, mandates, accomplishments and goals
federal Office of Dietary Supplements (ODS) was created in 1995
as a result of the Dietary Supplement Health and Education Act (DSHEA).
Funded with approximately $1 million at its inception, the ODS budget
has since expanded to $10 million -- a tiny fraction of the overall
NIH appropriation of $20 billion. What has the ODS been able to
accomplish with this modest funding, and what are its plans?
charged the ODS with two overall mandates:
explore more fully the potential role of dietary supplements
as a significant part of the efforts of the United States to
improve health care"
promote scientific study of the benefits of dietary supplements
in maintaining health and preventing chronic disease and other
establishing a long-range plan to meet these two mandates, the ODS
defined five major goals:
the role of dietary supplements in the prevention of disease
and reduction of risk factors associated with disease.
the role of dietary supplements in physical and mental health
the biochemical and cellular effects of dietary supplements
on biological systems and their physiological impact across
the life cycle.
scientific methods in the study of dietary supplements.
and educate scientists, health care providers, and the public
about the benefits and risks of dietary supplements.
first four of these goals are addressed primarily through research,
but also through various conferences and workshops. The ODS addresses
the fifth goal through a variety of educational activities, including
its website, and by developing two databases: IBIDS and CARDS.
the ODS plan points out, research is costly. Basic biological research,
animal studies, and small-scale epidemiological studies can range
in cost from less than one hundred to several hundred thousand dollars.
A large-scale, randomized clinical trial of efficacy and safety
can cost millions of dollars.
such challenges, the ODS has co-funded more than a dozen studies
in conjunction with the NIH Research Enhancement Awards Program.
acids and infants with ineffective intestinal metabolic function:
Infants with impaired intestinal function are more vulnerable
to dietary and bacterial toxins. This study will measure the
effect of three amino acids -- glutamate, glycine and cysteine
-- on glutatione synthesis. Glutathione may protect against
and cataracts in diabetics: Can antioxidants prevent the
production of specific toxic compounds found in the lens of
the diabetic eye -- compounds that are thought to contribute
to the development of cataracts?
and bone density loss with intense exercise: Athletes who
exercise intensely can experience decreases in bone density.
Can supplemental calcium intake prevent such bone loss?
and rheumatoid arthritis: Folate can affect the toxicity
and/or effectiveness of methotrexate treatment for rheumatoid
arthritis. This study in rats will examine the folate/methotrexate
interaction and can lead to an improved understanding of the
relationship between folate metabolism and the inflammation
and tissue injury seen in arthritis.
Arginine is an amino acid that influences protein synthesis
rates and cell proliferation markers. This study of the benefits
and risks of L-arginine supplementation in cancer patients will
improve understanding of how arginine may affect tumor stimulation
and zinc metabolism: Metallothionein is an enzyme that regulates
levels of zinc in different tissues throughout the body. This
research may offer unique insights into the role of specific
gene products and their effect on nutrition and metabolism.
and hearing loss with antibiotics: Antibiotic therapy sometimes
results in hearing loss. Can supplements either reduce or prevent
diet, and dental health in relation to cardiovascular disease
and stroke: The study will examine dental health, diet,
and supplement consumption in more than 50,000 men and 90,000
women currently enrolled in other federally-funded studies.
The hypothesis is that tooth loss leads to poor chewing and
reduced intake of dietary antioxidants and fiber, which would
increase the risk of heart disease.
John's wort and major depression: In this 8-week study, 336
patients with major depression will be given either St. John's
wort or a placebo or a selective serotonin reuptake inhibitor
(SSRI) that is commonly prescribed for depression. This study
has an 18-week extension for people who responded.
and cognitive function: Thiamin deficiency is a frequent
complication of alcoholism that can result in brain damage if
left untreated. MRI techniques will examine the effects of thiamin
deficiency and its treatment on neurochemical markers in the
brain of rats.
and alcoholism: This study will investigate a possible link
between low levels of serotonin and increased susceptibility
to alcoholism. Low serotonin levels could result from low dietary
intakes of the amino acid tryptophan or one of the micronutrients
that convert tryptophan to serotonin. This research may help
clarify the possible role of dietary tryptophan in preventing
alcoholism among high-risk populations.
Vanadium has been used to treat hyperglycemia in animals with
diabetes. This study will assess the toxicity and safety concerns
of vanadium use in humans.
and copper and their effect on the nervous system:
Deficiencies or excesses of copper and zinc have been associated
with several neuropathologic diseases of aging in humans, such
as Alzheimer's disease, epilepsy, and stroke. This study will
explore the modulatory actions of these two nutrients and their
effect on the nervous system.
ODS has also co-funded four centers for botanical research over
the past two years.
ODS has established a network of four botanical research centers
that conduct basic and clinical research on a variety of botanicals.
In collaboration with the National Center for Complementary and
Alternative Medicine (NCCAM), the Office of Research on Women's
Health, and the National Institute of General Medical Sciences,
two centers were established in 1999 and another two in 2000.
to Paul Coates, "We are especially pleased to have this network
of centers working together across the country, because they are
crucial to our long term mission. One of our goals is for these
centers to serve as resources for other organizations -- not just
NIH. These centers offer unique collections of expertise, ranging
from basic botanical to clinical research, that will be useful for
collaboration with other organizations in both public and private
sectors, for both regulatory agencies and industry."
Center for Dietary Supplements Research on Botanicals
fermented rice: potential mechanisms of action for cholesterol
reduction with implications for prevention of heart disease
tea extract and soy: for inhibition of tumor growth with
implications for treatment of cancer
John's wort: an herb used for relieving mild depression
botanicals: levels of bioactive compounds
of Illinois at Chicago Dietary Supplements Research Center
herbal supplements in relation to women's health issues,
including therapies for menopause
training in pharmacognosy (the study of natural products,
on botanicals for consumers and health professionals, including
an interactive website
Center for Dietary Supplement Research on Botanicals
effects of polyphenols in products such as soy, grapes, and
green tea: Health-promoting effects of polyphenols are generally
attributed to their antioxidant action, but other biological
mechanisms may be involved and will be explored. This research
agenda has important implications for heart disease, cancer,
osteoporosis and cognitive decline.
of Arizona Center for Dietary Supplement Research on Botanicals
medicine: ginger, turmeric and boswellia are widely used in
Ayurvedic medicine for the treatment of inflammatory diseases.
Researchers will identify the active constituents of these three
herbs and study their pharmacological activity. This research
will lead to clinical studies of arthritis and other chronic
inflammatory conditions including respiratory diseases such
ODS has organized or co-hosted several conferences and a wide variety
of workshops, both to promote the exchange of information and also
to identify the most pressing research needs. Conferences and workshops
enable scientists to get together and share what they know.
of nutrients and other bioactive components of dietary supplements:
defining the research agenda.
- cosponsored with Shape Up America!
supplements of potential benefit to patients with sickle cell
supplement use in children - cosponsored with National
Institute of Child Health and Human Development
and safety of medicinal herbs
in medicine - targets, diagnostics, and therapeutics
and health benefits of inulin and oligofructose
in health and disease
What role might supplements play
ODS workshops focused on melatonin -- in regard to aging
and helping people sleep.
of the research done overseas on botanicals has been criticized
as faulty in various ways; another workshop evaluated research
needs on the use and safety of medicinal herbs.
are thought to be important in reducing the risk of contracting
many serious chronic diseases -- especially heart disease,
cancer and diabetes; this workshop looked at frontiers
in antioxidant research.
workshop examined copper needs across the lifespan.
abuse and HIV/AIDS are difficult and challenging health
problems; one ODS workshop explored metabolic, endocrine and gastrointestinal
disorders in these conditions.
workshop focused on treatment of mental disorders with
essential fatty acids.
looked at safety issues in supplementing with lutein and zeaxanthin
-- two chemical compounds in plants that have shown promise in
preventing or slowing the development of macular degeneration,
one of the two major causes of blindness in America.
Bibliographic Information on Dietary Supplements (IBIDS)
IBIDS database has gathered
more than 400,000 citations of research on dietary supplements that
has been published throughout the world. IBIDS can be searched by
title, author and keywords. Every citation provides author name(s),
title, and publication data. Approximately two-thirds of the entries
include an abstract; when an entry does not, either an English translation
of the abstract was not available or there were copyright issues.
Access to Research on Dietary Supplements (CARDS)
CARDS database will provide
information on all federally funded research about dietary supplements.
Current plans are to begin with NIH-funded research. Fiscal 1999
records are now being entered into the database.
a database and making its information accessible on the Web is always
a challenging process. However, Coates is hopeful that CARDS will
be operational before the fall, and is himself looking forward to
finding out about the depth and breadth of dietary supplement research
funded by NIH.
the process of entering NIH research into the CARDS database is
going smoothly, they will expand the pipeline to include information
from other federal agencies that fund research on dietary supplements.
While agencies such as the Food and Drug Administration (FDA), US
Department of Agriculture (USDA), Centers for Disease Control &
Prevention (CDC) and others may provide some funding, Coates believes
the NIH proportion of the total research budget will be the highest.
and career development
but certainly not least, the ODS also encourages training and career
development for scientists in areas relevant to dietary supplements.
According to Coates, "This is a major area for us. We want to encourage
young scientists to understand that this field of research has plenty
to the future
sees several significant trends for ODS on the horizon. One is to
support training and career development. Coates administered such
programs on the university level and at NIH, and believes it is
vital to work with young investigators when they are looking at
career options. Another is to capitalize on the systematic literature
review to develop research agendas. Coates also anticipates that
recent conferences and workshops will lead to useful research opportunities.
example, the conference on dietary supplement use in children led
to three especially useful insights.
highlighted the need to evaluate use of dietary supplements
in several subpopulations. The ODS began investigating subpopulations
with children and is planning two more workshops: one on women
of reproductive age and another on the elderly. According to
Coates, "One way to establish priorities for research is to
recognize that there may be different needs and priorities at
different stages of the lifespan. Such workshops address our
third strategic goal of exploring biochemical effects and the
physiological impact of dietary supplements throughout the life
established some research priorities that the ODS is now developing
further. On 1 May 2001, the ODS is sponsoring a workshop on
"Dietary Supplement Use In Infants And Children" at the Pediatric
Academic Society's annual convention in Baltimore. Coates says
that "identifying and communicating research needs encourages
the scientific community to submit applications."
led to the recognition that we don't always know people's motives
for using supplements. For children in particular, who is making
the recommendations that they use supplements, and for what
purposes? What is shaping the children's behavior?
says, "There are some perfectly good reasons for thinking that some
supplements may be important for some children. If you look at calcium,
post-pubertal boys have more than adequate intakes, but many post-pubertal
girls fall short of meeting daily needs. Boys eat everything in
sight, but girls who have body image problems shy away from certain
kinds of foods. Also, children may have particular needs that are
different from adults, although we don't know yet which nutrients
or how much. However, other supplements may or may not be of value,
or might even be detrimental to children. These questions have not
been adequately studied. For example, is there a benefit or harm
to exposing kids to androgenic supplements such as DHEA? We simply
a modern research agenda
believes that systematic literature reviews will be even more valuable
than workshops and conferences for developing a research agenda
that addresses the ways in which dietary supplements are used today.
is an excellent example," Coates says. "The Senate appropriation
for ODS specifically encourages us to support research on ephedra.
Their language gives the ODS latitude to establish priorities --
'by engaging in a systematic review of current literature on ephedra
safety and efficacy for its currently used purposes of weight management,
energy enhancement and performance enhancement.' So we will be looking
at the current state of published evidence that relates to ephedra
use in those areas. What are the gaps in the knowledge that we can
fill with a well constructed agenda for research?"
to Coates, "Ephedra is a very appropriate example, because it serves
as a model for how we want to approach supplement ingredients in
current use. We felt invigorated by the Congressional language that
told us about doing an evaluation of evidence on one hand and developing
a research agenda on ephedra on the other hand. The experience we
glean from ephedra will serve as a excellent model for all of our
the controversies surrounding supplement safety and effectiveness
is an especially controversial supplement. An impartial review of
the literature on its safety and efficacy is urgently needed. Such
a review can guide an appropriate research agenda leading to scientific
consensus -- and thereby settle the public debate, not to mention
provide evidence for a few lawsuits.
controversy surrounds many other supplements as well. As we noted
recently on this website, three of the recommended dietary allowances
(RDAs) set by the national Institute of Medicine will be publicly
debated by experimental biologists. Even vitamin C is not free of
controversy: Does it prevent colds or ease their symptoms? Is 2000
mg an appropriate "safe upper level"?
scientific investigation is the best means of determining whether
a specific nutrient or supplement is both safe and effective --
and systematic review of current literature is the best method of
assessing "what we know now" and evaluating "what we need next."
reviews need to be as impartial and unbiased as possible, conducted
by people with a range of viewpoints and perspectives. Even though
all government agencies are, by definition, political in nature,
the Office of Dietary Supplements has brought a science-based point
of view to the question of what kinds of research to support and
seems well suited to lead the debate on what kinds of research to
M. Coates, PhD, Director of the Office of Dietary Supplements. Personal
communication, 25 and 27 April 2001.
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