[Federal Register Volume 78, Number 66 (Friday, April 5, 2013)]
[Notices]
[Pages 20672-20673]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-07901]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Literature Review Approach ``Identifying Research Needs for 
Assessing Safe Use of High Intakes of Folic Acid''; Request for 
Information and Comments

SUMMARY: The National Toxicology Program (NTP) at the National 
Institute of Environmental Health Sciences (NIEHS) in conjunction with 
the NIH Office of Dietary Supplements (ODS) is planning a workshop to 
identify research needs based on consideration of the state of the 
science related to the safe use of high intakes of folic acid. The NTP 
and the ODS invite comments on an approach document, ``Identifying 
Research Needs for Assessing Safe Use of High Intakes of Folic Acid,'' 
for review of the pertinent literature. The document is available on 
the NTP Folic Acid Request for Information (RFI) Web site (http://ntp.niehs.nih.gov/go/38143). Information gathered through this request 
will be used in prioritizing topics for the state of the science 
workshop.

DATES: The deadline for receipt of information and comments is May 28, 
2013.

ADDRESSES: Comments should be submitted at http://ntp.niehs.nih.gov/go/38143.

FOR FURTHER INFORMATION CONTACT: Abee L. Boyles, Ph.D., Health 
Scientist, Office of Health Assessment and Translation, Division of the 
NTP, NIEHS, PO Box 12233, MD: K2-04, Research Triangle Park, NC 27709; 
telephone: (919) 541-7886; fax: (301) 480-3230; email: 
[email protected]. Courier address: NIEHS, Room 2158, 530 Davis 
Drive, Morrisville, NC 27560 or Regan Bailey, Ph.D., R.D., Nutritional 
Epidemiologist, ODS, NIH, 6100 Executive Blvd., Room 3B01, Bethesda, MD 
20892-7517; telephone: (301) 496-0187; fax: (301) 480-1845; email: 
[email protected].

SUPPLEMENTARY INFORMATION: Background: The NTP in conjunction with the 
NIH ODS is planning a workshop to identify research needs based on 
consideration of the state of the science related to the safe use of 
high intakes of folic acid. The benefit of supplemental folic acid for 
pregnant women to prevent neural tube defects in their children is well 
established; at the same time, there is interest in understanding 
potential adverse health impacts from high intakes of folic acid. This 
project aims to identify research needs and inform the development of a 
research agenda for evaluating the safe use of high intakes of folic 
acid.
    Due to the vastness of the research on folate and folic acid, 
screening of the literature was undertaken to identify the potential 
adverse health effects for which further research might be warranted. 
An approach document, ``Identifying Research Needs for Assessing Safe 
Use of High Intakes of Folic Acid,'' is available on the RFI Web site 
(http://ntp.niehs.nih.gov/go/38143) and should be referenced in 
responding to the RFI. This document (1) outlines the approach used to 
screen the literature, (2) describes the results of the screening 
effort, and (3) proposes a list of health outcomes for discussion at 
the workshop. As background for the workshop, a literature review 
document on these health outcomes will be prepared using systematic 
review methodology.
    Humans require folate, a water-soluble B-complex vitamin, for the 
synthesis of nucleic acids and to provide methyl groups for biochemical 
reactions within cells. These functions are needed for everyday growth 
and cell division, including during critical periods of rapid growth 
and cell division such as embryonic development. Thus, folate is 
necessary for all individuals, but is especially important for women 
who may become pregnant. Evaluating the potential for adverse health 
effects associated with high folic acid intakes has been challenging 
because of the lack of systematic studies and other sources of evidence 
on this topic. In 1998, the Food and Nutrition Board of the Institute 
of Medicine set Dietary Reference Intakes that included the Recommended 
Dietary Allowances (RDAs) and tolerable upper intake levels (ULs)--the 
highest level of daily intake likely to pose no risk of adverse health 
effects to almost all of the population--for folic acid and other B 
vitamins. The folic acid UL (1000[mu]g) was established with the 
paucity of data available to the committee at the time; i.e., limited 
but suggestive evidence that excessive folate intake may precipitate or 
exacerbate neuropathy in vitamin B12-deficient individuals. Since this 
1998 publication that set the UL for folic acid, many publications have 
reported on health effects over a range of folic acid intakes. Some 
studies have raised concerns that high intake of folic acid may be 
associated with potential adverse health effects.
    Folate is present in the diet through its natural occurrence in 
food, as a food additive, and as an ingredient in dietary supplements. 
Naturally occurring folate is unlikely to be associated with potential 
adverse effects because it has lower bioavailability than folic acid 
and its consumption is also limited by the bulk and caloric content of 
foods. Therefore, the primary substance of interest for considering the 
safety of high intake is folic acid, the form of folate commonly added 
to foods and dietary supplements.
    Information gathered through this RFI will be used in prioritizing 
topics for the state of the science workshop. The date and location of 
the workshop have not yet been determined, but when set, will be 
announced in the Federal Register, the NIH Guide, and on the OHAT 
project Web site (http://ntp.niehs.nih.gov/go/38144). The overarching 
goals of this workshop are to identify research needs and inform the 
development of a research agenda for evaluating the safe use of high 
intakes of folic acid. The workshop will bring together experts from 
multiple disciplines including, but not limited to, epidemiology, 
nutrition, medicine, and toxicology.
    Request for Comments: The NTP and the ODS invite comments on an 
approach document, ``Identifying Research Needs for Assessing Safe Use 
of High Intakes of Folic Acid,'' for review of the pertinent 
literature, which is available at http://ntp.niehs.nih.gov/go/38143. 
They also request information on issues related to evaluating potential 
adverse health effects of high intakes of folic acid. The RFI Web site 
contains specific questions for the following topics:

[[Page 20673]]

     Health effects of most concern for high folate intake
     Assessments of folic acid intake and folate levels that 
are relevant and validated for high exposure
     Critical co-factors for the evaluation of potential health 
impacts of folic acid
     Experts in the field who should be considered for 
inclusion in the workshop
    Responses are invited from all interested parties, such as the 
nutrition research community, health professionals, educators, policy 
makers, industry, and the public. Responses to this RFI are voluntary. 
The comments collected will be analyzed and considered in planning and 
development of future initiatives. We do not intend to publish a 
summary of responses received or any other information provided, except 
very broad characterizations, such as the number of responses received. 
Despite this, proprietary, classified, or confidential information 
should not be included in your response. This RFI is for planning 
purposes only and is not a solicitation for applications or an 
obligation on the part of the U.S. Government to provide support for 
any ideas identified in response to it. Please note that the U.S. 
Government will not pay for the preparation of any comment submitted or 
for its use of that comment.
    Background Information on NTP and ODS: The NTP is an interagency 
program, established in 1978 (43 FR 53060) and headquartered at the 
NIEHS, whose mission is to evaluate agents of public health concern by 
developing and applying tools of modern toxicology and molecular 
biology. The NTP carries out literature analysis activities in the 
Office of Health Assessment and Translation and the Office of the 
Reports on Carcinogens within the Division of the NTP. The NTP also 
designs and conducts laboratory studies and testing programs and 
analyzes its findings to assess potential hazards to human health from 
exposure to environmental substances, including dietary supplements 
(see http://ntp.niehs.nih.gov/).
    The mission of the ODS is to strengthen knowledge and understanding 
of dietary supplements by evaluating scientific information, 
stimulating and supporting research, disseminating research results, 
and educating the public to foster an enhanced quality of life and 
health for the U.S. population. The purpose and responsibilities of the 
ODS are to explore more fully the potential role of dietary supplements 
as a significant part of the efforts of the United States to improve 
health care; to promote scientific study of the benefits of dietary 
supplements in maintaining health and preventing chronic disease and 
other health-related conditions; to conduct and coordinate scientific 
research within NIH relating to dietary supplements; to collect and 
compile the results of scientific research relating to dietary 
supplements, including scientific data from foreign sources; and to 
serve as the principal advisor to the Secretary of the Department of 
Health and Human Services and the Assistant Secretary for Health and to 
provide advice on issues relating to dietary supplements to the 
Director of NIH, the Director of the Centers for Disease Control and 
Prevention, and the Commissioner of the Food and Drug Administration 
(see http://ods.od.nih.gov/). The Dietary Supplement Health and 
Education Act of 1994 (Public Law 103-417, DSHEA), authorized the 
establishment of the ODS at the NIH in 1995.

    Dated: April 1, 2013.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2013-07901 Filed 4-4-13; 8:45 am]
BILLING CODE 4140-01-P