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| Number range  | **Testimony**                                        |
| CHAPTER       |                                                      |
|               | **Before the Subcommittee on Human Rights and        |
| ![](media/i   | Wellness**                                           |
| mage1.wmf){wi |                                                      |
| dth="1.118055 | **Committee on Government Reform**                   |
| 5555555556in" |                                                      |
| hei           | **United States House of Representatives**           |
| ght="1.148611 |                                                      |
| 111111111in"} |                                                      |
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| **Ongoing Research on Dietary Supplements at the National Institutes  |
| of Health**                                                           |
|                                                                       |
| ***Statement of***                                                    |
|                                                                       |
| **Paul M. Coates, Ph. D.**                                            |
|                                                                       |
| ***Director***                                                        |
|                                                                       |
| ***Office of Dietary Supplements***                                   |
|                                                                       |
| ***National Institutes of Health***                                   |
|                                                                       |
| ***U.S. Department of Health and Human Services***                    |
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![](media/image2.wmf)

> **For Release on Delivery**
>
> **Expected at 10:00 a.m.**
>
> **on Wednesday, September 22, 2004**

Mr. Chairman and Members,

Thank you for the opportunity to appear before you today representing
the Office of Dietary Supplements (ODS) at the National Institutes of
Health (NIH). I became Director of ODS in late 1999, and I had the
pleasure of appearing before the Committee two years ago, in July 2002.
At that time, I provided you with some details about the activities of
ODS and highlighted both the opportunities and the challenges associated
with developing good science in the field of dietary supplements.

Prior to highlighting ODS and other NIH efforts related to five
supplement ingredients that you identified -- folate, calcium, omega-3
fatty acids, glucosamine, and saw palmetto -- I want to give you a brief
update of our continuing and emerging collaborative investigations of
dietary supplements, particularly as they relate to reducing the risk of
chronic diseases.

## Health Effects of Dietary Supplement Ingredients

Dietary supplements are widely used by American consumers, often in
combination with other lifestyle measures such as diet and physical
activity, for their potential benefits in health promotion and disease
prevention. Surveys, such as the National Health and Nutrition
Examination Survey (NHANES), which is conducted by the Centers for
Disease Control and Prevention (CDC) and funded in part by NIH
organizations including ODS, show that 50% or more of American adults
use supplements on a regular basis, primarily vitamins and minerals, but
herbal and other supplements as well[^1]. There are many hopes pinned on
dietary supplements for the improvement of health and prevention of
disease, hopes that have been realized when some of them have been put
to modern scientific testing. Examples of these include:

-   Folic acid to reduce the risk of neural tube defects, one of the
    most common birth defects. As a result of this research, the CDC and
    other partners in the National Folic Acid Campaign aim to educate
    all women of childbearing age to consume 400 micrograms of synthetic
    folic acid daily from vitamin supplements and/or fortified foods in
    addition to eating food folate in a healthful diet;

-   Calcium to reduce the risk of osteoporosis. The NIH Consensus
    Development Conference in 1997 concluded that while the preferred
    source of calcium is through calcium-rich foods, both calcium
    supplements and calcium-fortified foods are other means by which
    optimal calcium intake can be reached for those who cannot meet this
    need by eating conventional foods;

-   Iron supplementation during pregnancy to prevent maternal anemia and
    delivery of premature infants;

-   Vitamin B-12 supplementation for those (particularly among the
    elderly) who cannot readily absorb food-bound vitamin B-12;

-   Vitamin and antioxidant supplementation to prevent progression of
    macular degeneration; and

-   Supplements promoting antioxidant activity generally to reduce the
    risk of oxidative damage from exposure to environmental agents.

Of the approximately 30,000 dietary supplements on the market in the
United States, there are many that have not undergone the rigorous
scientific testing needed to establish their efficacy and safety. Some
are under active investigation at the NIH, including:

-   Ginkgo biloba: does it prevent decline of cognitive function in
    older individuals?

-   Dietary phytoestrogens: do they prevent bone loss in postmenopausal
    women?

-   Selenium and vitamin E: alone or in combination, do they prevent
    prostate cancer?; and

-   Glucosamine and chondroitin: alone or in combination, do they
    diminish the pain associated with knee osteoarthritis?

Other dietary supplements have been shown to be potentially harmful to
some individuals; for example, research has shown that beta-carotene,
instead of reducing cancer risk, may actually increase lung cancer
incidence among cigarette smokers. For still others, there are signals
of concern (e.g., from adverse event reports) that need to be followed
up in a scientifically sound manner.

## The Expanding Role of ODS in Dietary Supplement Research

ODS was mandated by the Dietary Supplement Health and Education Act of
1994 (DSHEA) and was formally installed in the Office of the Director of
NIH in 1995. Its mission, based on a comprehensive strategic planning
process, is to "identify and foster research on the health benefits and
risks of these substances based on the merit of the underlying
scientific evidence."

Last year, ODS re-evaluated its Strategic Plan with input from a wide
range of stakeholders. I am pleased to announce that this Plan has just
been published and that it can be found on the ODS website
([http://ods.od.nih.gov](http://ods.od.nih.gov/)). The Strategic
Planning process helped us considerably in assessing how far we had come
in the past five years and in guiding ODS activities for the future. ODS
has been able to embark on a number of important activities, including:

-   Co-funding of dietary supplement research grants with other
    Institutes and Centers (ICs) at NIH. In FY 2004, ODS has been able
    to co-fund 90 grants with 15 NIH ICs for a total investment of
    approximately \$15 million;

-   Sponsoring conferences and workshops, again most often in
    collaboration with other ICs; since the inception of this program,
    ODS has sponsored nearly 100 such events;

-   Developing a series of fact sheets on vitamins and minerals, in
    collaboration with the NIH Clinical Center;

-   Initiating two important database efforts: the *International
    Bibliographic Information on Dietary Supplements (IBIDS)*, developed
    jointly with the National Agricultural Library of the U.S.
    Department of Agriculture (USDA), which cites roughly 750,000
    references to the world's literature, and *Computer Access to
    Research on Dietary Supplements (CARDS)* to track the Federal
    investment in dietary supplement research. The current CARDS data
    set describes the NIH investment from FY 1999 to FY 2003; over that
    period of time, NIH alone has invested over \$770 million in
    supporting nearly 2600 research projects related to dietary
    supplements; and

-   An especially important activity of ODS is its program of
    comprehensive Dietary Supplement Research Centers around the
    country. There are six of these multidisciplinary Centers (located
    at Purdue University/University of Alabama at Birmingham, Iowa State
    University/University of Iowa, University of Illinois at Chicago,
    University of California at Los Angeles, University of Arizona, and
    University of Missouri/Missouri Botanical Garden) whose primary
    focus is botanical dietary supplements. The Centers are jointly
    funded with the National Center for Complementary and Alternative
    Medicine (NCCAM) and the National Institute of Environmental Health
    Sciences (NIEHS); other NIH components, including the National
    Institute of General Medical Sciences (NIGMS) and the Office of
    Research on Women's Health (ORWH), also participate in funding these
    Centers.

More recently, the budget for ODS has grown, from \$3.5 million in FY
1999 to \$26 million in FY 2004. This has permitted expansion of our
research, education, and communications agenda into new and important
areas:

-   Evidence-based reviews of dietary supplement efficacy and safety, in
    collaboration with other NIH ICs and the Agency for Healthcare
    Research and Quality (AHRQ). (I will return to this activity later
    in my testimony.);

-   Surveys of dietary supplement use, e.g., the NHANES conducted by the
    CDC;

-   Development of a database of dietary supplement ingredients in
    collaboration with the USDA;

-   Development, validation, and dissemination of analytical methods and
    reference materials for dietary supplements, in collaboration with
    the Food and Drug Administration (FDA) and a number of private
    sector organizations[^2];

-   Development of a formal program related to the role of dietary
    supplements in health promotion and reduction of risk for chronic
    diseases;

-   Expansion of our information and communications program;

-   Expansion of training and career development activities; and

-   Participation in international research efforts.

In partnership with other NIH ICs, ODS funds research grants in areas
such as:

-   Folate-genome interactions in colorectal cancer;

-   Zinc nutrition and brain development in Southern Ethiopia;

-   Mechanisms of prostate cancer prevention by lycopene;

-   Aging, vitamin E, and immune function;

-   Chromium picolinate in the metabolic syndrome;

-   Mitochondrial rRNA methylation and effects of ethanol and
    S-Adenosyl-L-Methionine (SAMe);

-   Neuromodulatory effects of ginkgolides and bilobalides;

-   Conjugated linoleic acid effects on lipid synthesis;

-   Whether high dose B vitamins delay age-related decay; and

-   The role of St. John's Wort in the management of minor depression.

ODS sponsors workshops and conferences, again in collaboration with
other organizations both within and outside NIH. These meetings are
valuable sources of information in assisting us to shape upcoming
research activities. Some recent and upcoming conferences include:

-   The Role of SAMe in Treatment of Alcoholic Liver Disease. This led
    to issuing a Request for Applications (RFA) in 2002 with the
    National Institute on Alcohol Abuse and Alcoholism (NIAAA) and
    NCCAM; these 3 organizations jointly funded eight grants from this
    RFA;

-   Diet, DNA Methylation Processes and Health, sponsored by the
    National Cancer Institute (NCI) with participation by ODS, NIEHS,
    the National Institute of Diabetes and Digestive and Kidney Diseases
    (NIDDK), the National Heart, Lung, and Blood Institute (NHLBI), the
    National Institute of Child Health and Human Development (NICHD),
    and the FDA. This led to release of an RFA jointly sponsored by NCI
    and ODS and eventual funding of 10 grants;

-   Three conferences on Dietary Supplement Use in Children, in Women,
    and in the Elderly (with NICHD, NCCAM, NIA, ORWH and others);

-   Vitamin D and Health in the 21^st^ Century, jointly sponsored by ODS
    and NICHD; and

-   An NIH State-of-the-Science Conference on the Role of Multivitamins/
    multiminerals in Chronic Disease Prevention, to be organized by the
    NIH Office of Medical Applications of Research with sponsorship from
    ODS and many other NIH ICs.

The development of other new areas of investigation relies on forging
strategic partnerships with other agencies as well. A few current
examples include Interagency Agreements with:

-   The National Center for Health Statistics at CDC, to support
    improvements in the ability of NHANES to more accurately assess
    dietary supplement intake in the U.S., as well as biomarkers of
    supplement usage related to health outcomes;

-   AHRQ, to develop evidence reports of dietary supplement efficacy and
    safety. The first of these, on ephedra efficacy and safety in weight
    management and athletic performance enhancement, was published in
    early 2003[^3]; others have been completed (a series on the health
    effects of omega-3 fatty acids) or are underway on topics that
    include "Vitamin D Adequacy and Health" and "Relationship between
    Antioxidants in Berries and B Vitamins and Age-related
    Neurodegenerative Disorders";

-   FDA, to support the development and validation of analytical methods
    by the Association of Official Analytical Chemists (AOAC)
    International; and

-   The National Institute of Standards and Technology (NIST) in the
    Department of Commerce, to support development of standard reference
    materials.

We have worked with partners in the private sector in a number of areas:

-   Publication of an annual bibliography of outstanding research in
    dietary supplements, initially with the Consumer Healthcare Products
    Association. This effort, now fully under the auspices of ODS, is in
    its fifth year;

-   Publication of "Botanical Pharmacognosy and the Microscopic
    Characterization of Botanical Raw Materials" by the American Herbal
    Products Association was supported in part by ODS;

-   Publication of a summary of the conference "Dietary Supplement Use
    in the Elderly" in collaboration with the Foundation for the
    National Institutes of Health and Virgo Publishing Inc.;

-   Publication of \"What Supplements Are You Taking? Does Your
    Healthcare Team Know? It Matters and Here is Why\", a brochure for
    the elderly, jointly produced by FDA and ODS in collaboration with a
    number of private sector organizations;

-   Regular participation of ODS staff in educational and scientific
    sessions at industry meetings and expositions; and

-   A crucial effort is engaging with industry -- as well as other
    federal agencies, non-governmental organizations and academia -- to
    develop, validate, and disseminate analytical methods and reference
    materials for dietary supplements.

I would like to stress a theme that runs through all of the activities
that I have mentioned: all were developed in collaboration with other
organizations, both within and outside the NIH. They could not have been
accomplished otherwise. In my view, these collaborations are crucial to
the advancement of science and dissemination of information in the area
of dietary supplements. Further details of these and other interactions
can be found on the ODS website
([http://ods.od.nih.gov](http://ods.od.nih.gov/)).

Let me now turn to the five supplement ingredients that you have
identified as being of particular interest: folate, calcium, omega-3
fatty acids, glucosamine, and saw palmetto. I indicated earlier that the
Federal investment in dietary supplement research has been extensive
over the last five years. While the data are still being analyzed, I can
tell you that, taken together, research on these five ingredients has
accounted for roughly one-quarter of that investment. While much of the
funding has been directed to basic research, increasing attention has
been paid to conducting appropriate human studies. Some examples
include:

**Glucosamine**

A clinical trial of glucosamine and chondroitin sulfate for knee
osteoarthritis (Glucosamine/Chondroitin Arthritis Intervention Trial or
GAIT), jointly sponsored by NCCAM and the National Institute of
Arthritis and Musculoskeletal and Skin Diseases (NIAMS), has met its
recruitment goals and is due to be completed within a year.

**Saw palmetto**

A clinical trial of saw palmetto and Pygeum africanum for urinary
symptoms in men (Complementary and Alternative Medicine for Urinary
Symptoms, or CAMUS) was recently funded by NIDDK, NCCAM, and ODS.

**Omega-3 fatty acids**

As part of its program of evidence-based reviews of dietary supplement
efficacy and safety, ODS sponsored a series of AHRQ-contracted evidence
reports of the health effects of omega-3 fatty acids for a number of
conditions. Several of these have been published this year -- on
cardiovascular disease (CVD), asthma, and type 2 diabetes, among others
-- and several more will appear early in 2005. The evidence report on
CVD concluded that there was substantial and strong evidence for a
benefit of omega-3 fatty acids in the secondary prevention of CVD, but
that there was considerably less evidence for an effect on primary
prevention. Thus, while strong clues were obtained about the positive
health effects of omega-3 fatty acids on the future risk of disease in
people with existing CVD, the same cannot yet be said for the general
population. As a result of this report[^4], NHLBI and ODS convened a
working group earlier this year to assess future research needs related
to primary and secondary prevention in this area; the working group made
recommendations for clinical trials necessary to answer important
outstanding questions about omega-3 fatty acids[^5]. These
recommendations are currently being pursued.

**Calcium**

NIH funds considerable clinical research related to calcium. One
intramural NICHD study that I would like to draw to your attention is
the trial of Supplemental Calcium in Overweight People, which examines
the health effects of calcium supplements in overweight adults. In
addition, ODS has recently published a Fact Sheet on Calcium to inform
consumers about the health benefits of adequate calcium intake[^6]. All
Fact Sheets that ODS issues are regularly reviewed and updated as
necessary to reflect important advances in science.

**Folate**

Finally, based on results of the recently available NHANES data on
folate and vitamin B-12, along with developments in methodology for
their assessment, ODS is working with colleagues at NIH and other
Federal agencies in evaluating the measures that are employed to
determine health outcomes from intake of folate and vitamin B-12. There
is particular interest in the elderly, in whom intake of these vitamins
has been implicated in cognitive functioning and cardiovascular health.

## 

## Closing Remarks

Mr. Chairman and Members of the Committee, I thank you again for
inviting me to review the accomplishments of the Office of Dietary
Supplements at NIH, and to highlight some of its ongoing research
opportunities and challenges. I would be happy to answer your questions.

[^1]: Radimer K, Bindewald B, Hughes J, Irvin B, Swanson C, Picciano MF:
    Dietary supplement use by US adults: Data from the National health
    and Nutrition Examination Survey, 1999-2000. Amer J Epidemiol
    160:339-349, 2004.

[^2]: Saldanha LG, Betz JM, Coates PM: Development of the analytical
    methods and reference materials program for dietary supplements at
    the National Institutes of Health. J AOAC Int. 87:162-165, 2004.

[^3]: Shekelle PG, Hardy ML, Morton SC et al: Efficacy and safety of
    ephedra and ephedrine for weight loss and athletic performance: a
    meta-analysis. JAMA 289:1537-1545, 2003.

[^4]: http://www.ahrq.gov/clinic/tp/o3cardtp.htm

[^5]: http://www.nhlbi.nih.gov/meetings/workshops/omega3-summary.htm

[^6]: http://ods.od.nih.gov/factsheets/calcium.asp