## ![](media/image1.png){width="0.9798611111111111in" height="0.9895833333333334in"}Jean Mayer

United States Department of Agriculture

Human Nutrition Research Center on Aging

At Tufts University

**Committee on Government Reform**

**Subcommittee on Human Rights and Wellness**

**Representative Dan Burton, Chairman**

**September 22, 2004**

**Rayburn Building, Washington, DC**

### Dietary Supplements: Nature's Answer to Cost Effective Preventative Medicine

**Testimony by:**

**Jeffrey B. Blumberg, PhD, FACN, CNS**

**Friedman School of Nutrition Science and Policy**

**Jean Mayer USDA Human Nutrition Research Center on Aging**

**Tufts University**

**Boston, MA**

**The Role of Folic Acid and Other Dietary Supplements**

**in the Promotion of Health and Prevention of Chronic Disease**

I am a Professor of Nutrition at the Friedman School of Nutrition
Science and Policy and the Associate Director of the Jean Mayer USDA
Human Nutrition Research Center on Aging at Tufts University. I also
serve as a non-paid member of the Scientific Advisory Board of the
Dietary Supplement Education Alliance. I have been investigating the
role of dietary supplements in the promotion of health and prevention of
chronic disease for almost 25 years. It is now indisputable that
nutrition is a key component of any disease prevention strategy and
optimal intakes of vitamins, minerals and other nutrients are critical
to maintaining wellness. Virtually every nutrition-monitoring survey
reveals that most Americans fail to achieve these intakes through their
usual diets. Fortunately, dietary supplements represent an affordable,
effective, and practical tool to help solve this problem and, thus,
ultimately reduce healthcare costs. While I will illustrate this
principle with the example folic acid, it is important to recognize
there is an extensive body of scientific evidence demonstrating the
health benefits of other dietary supplements as you are hearing from
other experts today.

Folic acid is a B vitamin essential to the activity of more than a dozen
enzymes, amino acid metabolism, and DNA formation. Inadequate intake of
folic acid has been associated with anemia, some forms of cancer, heart
disease, poor pregnancy outcomes (including preterm delivery, infant low
birth weight, fetal growth retardation), and birth defects, most
notably, neural tube defects (NTD) leading to spina bifida and
anencephaly but also including cleft lip and palate, limb deficiencies,
conotruncal defects of the heart, and Down syndrome. The richest dietary
sources of folic acid are liver, mushrooms dried beans, green leafy
vegetables, and since 1998, enriched grains fortified with this vitamin.
The Recommended Dietary Allowance for folic acid is 400 µg daily. Usual
intakes of folic acid before fortification were 200 µg but are now
estimated to be about 300 µg with much lower intakes in people following
low carbohydrate diets and avoiding fortified breads and other cereals.
However, it is important to understand that many people have a greater
need for folic acid, including pregnant and lactating women, people who
consume alcoholic beverages or take certain medications (e.g., aspirin,
methotrexate, pyrimethamine, trimethoprim), patients with certain
inflammatory conditions of the intestine (e.g., enteritis with
malabsorption such as sprue), and the elderly.

For the last five years, Center for Disease Control and Prevention and
the Institute of Medicine has recommended that all women capable of
becoming pregnant should consume 400 µg/day of synthetic folic acid from
supplements or fortified food in addition to consuming food folate from
a variety of dietary sources. The scientific basis of this
recommendation included data from population-based studies and
randomized clinical trials as well as extensive experimental studies.
Folic acid supplements have been proven to be the most effective and
reliable method to reduce the probability of NTD. Nonetheless,
two-thirds of American women of child-bearing age do not follow this
advice and one of every thousand babies in the US is born with an NTD.
The Lewin Group analysis calculated that over the next five years \$1.3
billion in health care costs could be saved if these women took a daily
supplement containing 400 µg folic acid.

But folic acid supplements are not just for women. The benefits of daily
folic acid supplementation extend well beyond reducing the risk of NTD
and other birth defects. Observational studies consistently reveal that
men and women taking supplements containing folic acid have the lowest
blood levels of the amino acid homocysteine. Some evidence suggests that
lowering homocysteine levels could reduce the risk of heart disease by
20 percent. Elevated levels of homocysteine are a significant,
independent risk factor for atherosclerotic vascular disease in the
coronary, cerebral, and peripheral vessels and for arterial and venous
thromboembolism. Many studies reveal that elevated homocysteine may
enhance the effect of other established vascular risk factors such as
hypertension and smoking. Low intakes of folic acid have now been shown
to be the primary determinant of mild-to-moderate elevations of
homocysteine. Randomized clinical trials investigating the effect of
folic acid supplements on risk of heart disease, stroke, and dementia
are now being supported with Federal funds.

Folate inadequacy has a pro-carcinogenic effect by interfering with
normal DNA synthesis and regulation (via methylation reactions). An
increased risk for some forms of cancer has been associated with poor
folate status in several epidemiological studies, with the strongest
evidence linked to colorectal cancer. However, studies have also
suggested that the increased risk of breast cancer associated with
regular alcohol consumption may be reduced by an increased intake of
folic acid from dietary supplements. Recent experimental research has
shown that low consumption of folic acid impairs the integrity of the
genome, particularly tumor suppressor genes, and this effect can be
reversed by supplementing the diet with folic acid.

While many different factors contribute to the risk of poor health and
chronic disease, we know that diet and the intake of specific nutrients
play a key role in the prevention of cancer, diabetes, heart disease,
infectious diseases, macular degeneration, osteoporosis, and other
conditions. The power of nutrition to promote health is well
established. We need now to find ways to encourage Americans to choose
healthful dietary patterns and increase their intake of key nutrients
with fortified foods and dietary supplements. If we succeed in doing so,
both the personal burden of disease carried by Americans and the
associated enormous expenditure for their healthcare will be
substantially reduced.

Thank you.

[Selected References]{.underline}

*Neural Tube Birth Defects and Other Pregnancy-related Topics*

Centers for Disease Control and Prvention. Neural tube defect
surveillance and folic acid intervention -- Texas-Mexico border
1993-1998. MMWR Morb Mortal Wkly Rep 2000: 49:1-4.

Scott JM, Weir DG, Kirke PN. Folate and neural tube defects. In: Bailey
LB, ed. Folate in health and disease. New York: Marcel Dekker,
1995;329-60.

Shaw GM, Schaffer D, Velie EM, et al. Periconceptional vitamin use,
dietary folate, and the occurrence of neural tube defects. Epidemiology
1995;6:219-26.

Ellison J, Clark P, Walker ID, Greer IA. Effect of supplementation with
folic acid throughout pregnancy on plasma homocysteine concentration.
Thromb Res 2004;114:25-7.

Megahed MA, Taher IM. Folate and homocysteine levels in pregnancy. Br J
Biomed Sci. 2004;61:84-7.

Yang Q, Atkinson M, Erickson JD. Method of weighted proportion of
reproductive-aged women taking folic acid supplements to predict a
neural tube defect rate decline. Birth Defects Res 2003;67:959067.

*Atherosclerotic Vascular Diseases*

Boushey CJ, Bereford SA, Omenn GS, Motulsky AG. A quantitative
assessment of plasma homocysteine as a risk factor for vascular disease.
Probably benefits of increasing folic acid intakes. JAMA
1995:274:1049-57,

Brattstrom LE. Vitamins as homocyteine-lowering agents. J Nutr
1996:126:1276S-80S.

Kalra DK. Homocysteine and cardiovascular disease. Curr Atheroscler Rep
2004;6:101-6.

Kelly JJ, Kohlhagen J. Atherosclerosis and Folic Acid Supplementation
Trial: untangling the web of cardiac risk in chronic kidney disease.
Nephrology 2004;9:112-3.

Moat SJ, Lang D, McDowell IF, Clarke ZL, Madhavan AK, Lewis MJ,
Goodfellow J. Folate, homocysteine, endothelial function and
cardiovascular disease. J Nutr Biochem 2004;15:64-79.

Paradisi G, Cucinelli F, Mele MC, Barini A, Lanzone A, Caruso A.
Endothelial function in post-menopausal women: effect of folic acid
supplementation. Hum Reprod 2004;19: 1031-5.

Pena AS, Wiltshire E, Gent R, Hirte C, Couper J. Folic acid improves
endothelial function in children and adolescents with type 1 diabetes. J
Pediatr 2004;144:500-4.

Refsum H, Ueland PM, Nygard O, Vollset. Homocysteine and cardiovascular
disease. Ann Rev Med 1998;49:31-62.

Splaver A, Lamas GA, Hennekens CH. Homocysteine and cardiovascular
disease: biological mechanisms, observational epidemiology, and the need
for randomized trials.

Am Heart J 2004;148:34-40.

*Cancer*

Basten GP, Hill MH, Duthie SJ, Powers HJ. Effect of folic acid
supplementation on the folate status of buccal mucosa and lymphocytes.
Cancer Epidemiol Biomarkers Prev 2004;13:1244-9.

Choi SW, Mason JB. Folate and carcinogenesis: an integrated scheme. J
Nutr 2000;130: 129-32.

Jacob RA, Greta DM, Taylor PC, et al. Moderate folate depletion
increases plasma homocysteine and decreases lymphocyte DNA methylation
in postmenopausal women. J Nutr 1998;128:1204-12.

Majumdar AP, Kodali U, Jaszewski R. Chemopreventive role of folic acid
in colorectal cancer. Front Biosci 2004;9:2725-32.

Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate
intake and the risk of breast cancer. JAMA 1999;281:1632-7.

Diculescu M, Ciocirlan M, Ciocirlan M, Pitigoi D, Becheanu G, Croitoru
A, Spanache S. Folic acid and sulfasalazine for colorectal carcinoma
chemoprevention in patients with ulcerative colitis: the old and new
evidence. Rom J Gastroenterol 2003;12:283-6.

*Other Health-related Topics*

Iskandar BJ, Nelson A, Resnick D, Pate Skene JH, Gao P, Johnson C, Cook
TD, Hariharan N. Folic acid supplementation enhances repair of the adult
central nervous system. Ann Neurol 2004;56:221-7.

Lamers Y, Prinz-Langenohl R, Moser R, Pietrzik K. Supplementation with
\[6S\]-5-methyltetrahydrofolate or folic acid equally reduces plasma
total homocysteine concentrations in healthy women. Am J Clin Nutr
2004;79:473-8.

Millar WJ. Folic acid supplementation. Health Rpt 2004;15:49-52.

Morrell MJ. Folic acid and epilepsy. Epilepsy Curr 2002;2:31-4.

Schwammenthal Y, Tanne D. Homocysteine, B-vitamin supplementation, and
stroke prevention: from observational to interventional trials. Lancet
Neurol. 2004;8:493-5.

Whittle SL, Hughes RA. Folate supplementation and methotrexate treatment
in rheumatoid arthritis: a review. Rheumatology 2004 Jan 6 \[Epub ahead
of print\]

Woitalla D, Kuhn W, Muller T. MTHFR C677T polymorphism, folic acid and
hyperhomocysteinemia in levodopa treated patients with Parkinson\'s
disease. J Neural Transm Suppl 2004;68:15-20.

McLean RR, Jacques PF, Selhub J, Tucker KL, Samelson EJ, Broe KE, Hannan
MT, Cupples LA, Kiel DP. Homocysteine as a predictive factor for hip
fracture in older persons. N Engl J Med 2004;13;350:2042-9.

Submitted by:

Jeffrey Blumberg, PhD, FACN, CNS

Associate Director and Professor

Friedman School of Nutrition Science and Policy

Jean Mayer USDA Human Nutrition Research Center on Aging

Tufts University

711 Washington Street

Boston, MA 02111

tel: 617-556-3334

Fax: 617-556-3295

EM: jeffrey.blumberg@tufts.edu