Could a mandated food additive aimed at better fetal development be a risk for seniors?

July 21, 2003

(Philadelphia, PA) - Growing older carries more risks, among them the risk for vitamin B-12 deficiency. For most people, B-12 deficiency is more commonly associated with anemia than with its more subtle but potentially grave complications. Emerging evidence points to B-12 deficiency as an increasingly common reason behind high levels of homocysteine in the blood.

While homocysteine, a non-essential amino acid, is normally present in low concentrations in the blood, individuals with high levels have a significantly greater risk for cardiovascular diseases, although the direct link has not yet been established. What is known, however, is that cardiovascular diseases are responsible for nearly half of all deaths in the US each year.

What are the possible adverse consequences from vitamin B-12 deficiency? Which populations are most at risk and is there another vitamin deficiency of equal concern? These and other questions are part of a presentation entitled "Vitamin B-12: Deficiency, Evolution in Diagnosis, and At-Risk Populations" being given by Ralph Green, MD, Professor and Chair of the Department of Pathology at the University of California-Davis Health System, and Pathologist-in-Chief at the University of California-Davis Medical Center, Sacramento, CA. Dr. Green is offering his remarks during the 55th Annual Meeting of the American Association for Clinical Chemistry (AACC) in Philadelphia, PA, July 20-24, 2003. More than 16,000 attendees are expected.


The normal metabolism of homocysteine requires at least three, and probably four, vitamins: vitamin B-12, folic acid, vitamin B-6, and riboflavin. As with deficiencies of B-12, deficiencies of folic acid (folate) can cause high levels of homocysteine. The metabolism of these two vitamins is closely intertwined and deficiency of either one produces identical effects of anemia. Deficiencies of both are commonly found among the elderly. While alike, and work hand-in-hand to execute many of the body's critical functions, they also differ.

Vitamin B-12

Vitamin B-12 is the largest known vitamin; a complex molecule, it is stored in the liver, kidneys, and tissues of the body. B-12 is consumed through food sources such as meat, liver, fish, yogurt, and many dairy products, and can also be taken through injections and supplements. B-12 is important as it helps build red blood cells and keeps the nervous tissues in tip-top shape. Conversely, B-12 deficiency is often present in persons with high levels of homocysteine, which frequently are encountered in cardiac and other vascular disorders.

B-12 deficiency can also result in anemia (lower levels of red blood cells) and damage to the nervous system. Common symptoms for the deficiency are fatigue from anemia, mental confusion and sensory and movement difficulties.

Vegans (strict vegetarians who do not eat fish or eggs), and those taking medications which block stomach acid production and thus B-12 absorption, are at highest risk for the deficiency. In developing countries in Central and South America as well as in Africa and Asia, the prevalence rates for B12 deficiency among children, teenagers and pregnant women range from 10 to 30 percent. Overall, the US prevalence rates for children, teenagers, pregnant women and other women is believed to be low. The long-term consequences of B-12 deficiency are unknown, but some speculate that B-12 deficiency may in some respects mimic iron deficiency, thereby affecting the brain and causing postnatal behavioral and learning disabilities.

It is estimated that up to 15 percent of those over age 60 have varying degrees of B-12 deficiency. Moreover, three percent of those over 65 will develop pernicious anemia, a reduction in the number of red blood cells due to malabsorption of the vitamin caused by a failure of the gastric mucosa to secrete a substance, intrinsic factor, necessary for normal B-12 absorption. H-pylori, a corkscrew shaped bacterium responsible for a variety of stomach ailments, including gastric and duodenal ulceration and atrophy of the stomach lining, occurs quite commonly in some populations. When H-pylori infection is present the normal absorption of BV-12 is impaired.

Folic Acid

Not long ago, the most common, modifiable cause of high levels of homocysteine was folic acid deficiency.

Before 1998 there were between 4,000-5,000 children born with neural tube defects annually in the US. Neural tube defects occur in human embryos and result in developmental defects. The defects are caused by an improper fusion of the embryo's brain and/or spinal cord that takes place during a series of minutely timed sequences occurring between the 16th and 25th days of gestation. The most extreme cases of developmental defects result in the total absence of a brain, called anencephaly. In less severe cases, it results in spina bifida.

Until recently, women who had one neural tube defect pregnancy were at higher risk of recurrence in subsequent pregnancies. In the mid-1990s, studies of women in Ireland, Hungary and other European countries determined that women who had previously had neural tube defect pregnancies but later received supplemental amounts of folic acid lowered their risk of neural tube defects in subsequent pregnancies.

As no educational campaign was likely to reach women within the first 25 days of pregnancy to urge them to take supplemental folic acid, the US government in l998 mandated folic acid be added to all cereals and grains (pasta, bread, and other cereal-grain product), a nutritional outreach effort similar to those undertaken successfully in the past. The amount of folate to be added was "enough to prevent neural tube defects in most cases, but not enough so as to constitute a risk."

Since the American diet has been fortified with folic acid, researchers have observed a 20 percent overall reduction in neural tube defects. They have also seen folic acid deficiency in the nation overall plummet from 21 percent to just one percent.

Good News, Bad News

Folate deficiency causes a type of anemia and large amounts of folic acid reverse or prevent this anemia as well as a similar anemia caused by B-12 deficiency. Mandated folic acid in the diet, may, however, be eliminating the most obvious manifestation of B-12 deficiency in the elderly: anemia. Because the vitamins are so similar, consumption of folic acid may be counteracting fatigue, the most classic sign of anemia and B-12. The concern among physicians like Green is that without symptoms of fatigue many elderly people will forego visiting their physician, who would diagnose B-12 deficiency, if present. The longer their B-12 deficiency goes undetected, the longer their brains and nervous systems will undergo progressive deterioration due to the B-12 deficiency, culminating in a greater risk for the Alzheimer's--like dementia as well as paralysis that can result from B-12 deficiency.

Diagnosing B-12 Deficiency

Prevention of B-12 deficiency is therefore important not just for the potential consequences to the heart, but to prevent dementia in the elderly. How, then to best identify whether a person is deficient in B-12?

Research is evolving to better ways to identify true B-12 deficiency. The first generation of testing assays, developed in the late 1940s, measured only the extant levels of B-12 in the blood. Second generation testing looked for deficiencies in B-12 (and/or folic acid) by finding high levels of homocysteine in the blood. A newer generation of testing is known as the Methylmalonic Acid (MMA) test, which is more sensitive and specific than the other tests. When deficiencies in B-12 are present, MMA levels rise. Due to its cost, however it is usually used only for confirmatory testing. The latest state-of-the-art laboratory test is an assay that measures only the portion of B-12 that is attached to the carrier protein transcobalamin. Tests using this assay, known as TC, are currently underway in a number of labs including Green's across the country.


The key to preventing B-12 deficiency is a balanced diet, particularly among the elderly. But some individuals, despite following a nutritious diet plan, may not be able to absorb a food's vitamins due to problems such as a diseased stomach. Therefore, to rule out (or in) B-12 deficiency, screening is recommended. Following a diagnosis, Dr. Green recommends patients begin regular monthly injections of B-12 or take large dose B-12 supplements by mouth.


Because we are eating more folic acid in our diet, the elderly and those who care for them should ensure they have not become B-12 deficient. Annual screening is therefore recommended. Since the United States and Canada are the only two countries to fortify with folic acid to better assure that all babies are born healthy, the government should also encourage deficiency screening of the elderly to ascertain that such laudable efforts do not come at the expense of inadvertent harm to others.
The American Association for Clinical Chemistry (AACC) is the world's most prestigious professional association for clinical laboratorians, clinical and molecular pathologists, and others in related fields. AACC's members are specialists trained in the areas of laboratory testing, including genetic disorders, infectious diseases, tumor markers and DNA. Their primary professional commitment is utilizing tests to detect, treat and monitor disease.

***Editor's Note: To schedule an interview with Dr. Green, please contactDonna Krupa at 703-527-7357 (direct dial), 703-967-2751 (cell) or Or contact the AACC Newsroom at: 215-418-2429 between 8:00 AM and 4:00 PM EST July 20-24, 2003.

SUNDAY, JULY 20, 2003 @ 12:00 NOON
Pennsylvania Convention Center
Room: 303B
Tel.: 215-418-2429

American Association for Clinical Chemistry

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