Research Studies

Vitamin B12 status and rate of brain volume loss in community-dwelling elderly

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ABSTRACT
Objectives: To investigate the relationship between markers of vitamin B12 status and brain volume loss per year over a 5-year period in an elderly population.
Methods: A prospective study of 107 community-dwelling volunteers aged 61 to 87 years without cognitive impairment at enrollment. Volunteers were assessed yearly by clinical examination, MRI scans, and cognitive tests. Blood was collected at baseline for measurement of plasma vitamin B12, transcobalamin (TC), holotranscobalamin (holoTC), methylmalonic acid (MMA), total homocysteine (tHcy), and serum folate.
Results: The decrease in brain volume was greater among those with lower vitamin B12 and holoTC levels and higher plasma tHcy and MMA levels at baseline. Linear regression analysis showed that associations with vitamin B12 and holoTC remained significant after adjustment for age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, ApoE _4 status, tHcy, and folate. Using the upper (for the vitamins) or lower tertile (for the metabolites) as reference in logistic regression analysis and adjusting for the above covariates, vitamin B12 in the bottom tertile (_308 pmol/L) was associated with increased rate of brain volume loss (odds ratio 6.17, 95% CI 1.25-30.47). The association was similar for low levels of holoTC (_54 pmol/L) (odds ratio 5.99, 95% CI 1.21-29.81) and for low TC saturation. High levels of MMA or tHcy or low levels of folate were not associated with brain volume loss.
Conclusion: Low vitamin B12 status should be further investigated as a modifiable cause of brain atrophy and of likely subsequent cognitive impairment in the elderly. Neurology® 2008;71:826-832

 

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Vitamin B deficiencies are common in elderly people

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LEUVEN, BELGIUM. An international team of researchers have confirmed that elderly people often suffer from a deficiency of vitamins B-6, B12 and folic acid. Their investigation involved 99 healthy young people (aged 19-55), 64 healthy elderly subjects (aged 65-88), and 286 elderly hospitalized patients (aged 61-97). The researchers measured the blood concentrations of the vitamins in all subjects as well as the concentration of certain metabolic products that tend to build up if a vitamin deficiency is present. They found that 9% of the healthy elderly subjects had a low vitamin B-6 level as compared to more than 51% for the hospitalized patients. Corresponding numbers for vitamin B12 and folic acid were 6% and 5%, and 5% and 19% respectively. Of perhaps greater significance was the finding that in 63% of the healthy elderly subjects and in 83% of the elderly patients the researchers observed an increased serum concentration of one or more of the metabolic products that indicate a deficiency in vitamin B-6, B12 or folate. Thus an elevated level of the metabolite (methylmalonic acid), which indicates a B12 deficiency, was found in 23% of the healthy elderly people and in 39% of the elderly hospitalized patients. Recent experiments have shown that weekly injections of vitamin B12, B-6, and folate are highly effective in normalizing the elevated metabolite concentrations in elderly people.

Joosten, Etienne, et al. Metabolic evidence that deficiencies of vitamin B12 (cobalamin), folate, and vitamin B-6 occur commonly in elderly people. American Journal of Clinical Nutrition, Vol. 58, No. 3, September 1993, pp. 468-76

Vitamin B12 Deficiency easy to avoid

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KINGSTON, CANADA. Many older people suffer from a deficiency of vitamin B12 (cobalamin). A low intake of animal protein, the use of medications to reduce stomach acid, a Helicobacter pylori infection, an inflammation of the stomach lining, and problems with the pancreas can all contribute to the development of a deficiency. Medical researchers at Queen’s University now report that daily supplementation with a multivitamin containing 2.6 – 37.5 micrograms of vitamin B12 is enough to prevent a cobalamin deficiency in most older healthy people. Their study involved 242 active, relatively healthy men and women aged 65 years or older. Sixty-six (27.3 per cent) of the volunteers had been taking a daily multivitamin containing 2.6 – 37.5 micrograms of vitamin-B12 for at least six months.

All volunteers had blood samples drawn for the measurement of cobalamin level as well as the levels of the related metabolites methylmalonic acid (MMA), homocysteine (HCYS) and methylcitric acid (MCTR). Thirty- seven (15.3 per cent) of the 242 participants were deficient in cobalamin (level below 165 pmol/L). Of these 37 only 2 were taking multivitamins. An elevated level of MMA was found in 53 participants of whom 46 (87 per cent) were not taking multivitamins. An elevated level of homocysteine was found in 17 participants of whom 16 were not supplementing. The researchers conclude that oral supplementation with 25 micrograms/day or higher may be sufficient to prevent vitamin B12 deficiency in a large proportion of older people. They caution though that their findings cannot be extrapolated to frail or sick old people who may require larger doses to avoid deficiency.

Garcia, Angela, et al. Is low-dose oral cobalamin enough to normalize cobalamin function in older people? Journal of the American Geriatrics Society, Vol. 50, August 2002, pp. 1401-04

Vitamin B12 deficiency common after stomach surgery

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PHILADELPHIA, PENNSYLVANIA. It is becoming increasingly clear that a vitamin B12 deficiency can have serious consequences, particularly in elderly people. A vitamin B12 deficiency can be misdiagnosed as Alzheimer’s disease, amyotrophic lateral sclerosis (Lou Gehrig’s disease), spinal cord compression, or alcoholic or diabetic peripheral neuropathy. A vitamin B12 deficiency is also associated with elevated homocysteine levels that in turn have been linked to a significantly increased risk for atherosclerosis and heart disease. The elderly are at special risk for being deficient in vitamin B12 and, as researchers at the Philadelphia Veterans Affairs Medical Centre report, so are people who have had stomach surgery for peptic ulcers and similar conditions. The study involved 61 patients with a mean age of 63 years who had undergone gastric surgery as far back as 30 years ago and 107 controls. The researchers found that 31 per cent of the surgery group had a vitamin B12 deficiency as compared to 2 per cent among the controls. The presence of a deficiency was established through measurements of the levels of vitamin B12, total homocysteine, and methylmalonic acid in the blood. The deficiencies were corrected by daily injections of 1000 micrograms of vitamin B12 for five days followed by monthly injections. Folic acid supplementation (1 mg/day) was also used. The researchers recommend that physicians ensure that those of their patients who had gastric surgery, no matter how long ago, be checked periodically for a vitamin B12 deficiency. If one is found, the patients should be given lifelong vitamin B12 therapy (periodic intramuscular injections).

Sumner, Anne E., et al. Elevated methylmalonic acid and total homocysteine levels show high prevalence of vitamin B12 deficiency after gastric surgery. Annals of Internal Medicine, Vol. 124, No. 5, March 1, 1996, pp. 469-76

Vegetarians are vitamin B12 deficient

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SYDNEY, AUSTRALIA. It is generally assumed that vitamin B12 deficiencies are rare among people consuming a varied diet. However, there is some question whether vegetarians get enough B12 as it is not present in plants. Researchers at the Sydney Adventist Hospital have just completed a study aimed at resolving this question. Their study involved 245 Adventist ministers who were either lactoovovegetarians or vegans. The average age of the ministers was 46 years (range 22 to 80 years) and most of them had been vegetarians for over 20 years. The study participants filled out a diet questionnaire and had a fasting blood sample drawn for a 20-test biochemical profile including vitamin B12 concentrations. The mean vitamin B12 level was 199 pmol/L and 73 per cent of the ministers had a level below the recommended lower limit of 221 pmol/L. Vitamin B12 concentrations were also measured in a control group of 53 ministers who consumed fish, poultry or red meat on a regular basis. In this group 40 per cent had vitamin B12 concentrations below the recommended lower limit; this indicates that vitamin B12 deficiency is widespread even among non-vegetarians.

Additional tests showed that the vitamin B12 deficiencies observed among lactoovovegetarians were due to dietary deficiencies rather than to malabsorption. The researchers conclude that as many as 73 per cent of Australian vegetarians are vitamin B12 deficient and recommend that they increase their intake either from vitamin B12-containing foods (animal products), from supplements or from vitamin B12- fortified foods.

Hokin, Bevan D. and Butler, Terry. Cyanocobalamin (vitamin B12) status in Seventh-day Adventist ministers in Australia. American Journal of Clinical Nutrition, Vol. 70, September 1999, pp. 576S- 78S

The homocysteine connection

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This is not however the end of the story. Most vegans show adequate B12 levels to make clinical deficiency unlikely but nonetheless show restricted activity of B12 related enzymes, leading to elevated homocysteine levels. Strong evidence has been gathered over the past decade that even slightly elevated homocysteine levels increase risk of heart disease and stroke and pregnancy complications. Homocysteine levels are also affected by other nutrients, most notably folate. General recommendations for increased intakes of folate are aimed at reducing levels of homocysteine and avoiding these risks. Vegan intakes of folate are generally good, particularly if plenty of green vegetables are eaten. However, repeated observations of elevated homocysteine in vegans, and to a lesser extent in other vegetarians, show conclusively that B12 intake needs to be adequate as well to avoid unnecessary risk.

Vitamin B12 deficiency and ulcer drugs

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DENVER, COLORADO. Researchers at the University of Colorado School of Pharmacy warn that prolonged use of acid-suppressing drugs such as cimetidine (Tagamet), ranitidine (Zantac) and omeprazole (Losec) can lead to a serious vitamin-B12 deficiency. They cite the case of a 78-year-old non-vegetarian, white woman with GERD (gastroesophageal reflux disease) who had been taking cimetidine or ranitidine for 4.5 years. She was started on cimetidine (300 mg four times daily) in February 1990, which was changed to ranitidine (150 mg twice daily) in April 1993. Her vitamin B12 level was normal (413 pg/mL) in August 1992, but by June 1994 it had decreased to 256 pg/mL and her homocysteine level had increased dramatically to 27.3 micromol/L. Note: A homocysteine level above 10 micromol/L vastly increases the risk of atherosclerosis and stroke with a 5 micromol/L increase corresponding to a 70 per cent increase in the risk of heart disease and a 50 per cent increase in stroke risk.

The patient was started on 1000 micrograms/day of sublingual vitamin B12 supplementation and by November 1994 her level was back up to 517 pg/mL and her homocysteine level was down to 20.3 micromol/L. Further improvements were observed in March 1998 when her vitamin B12 level was up to 629 pg/mL and homocysteine was down to 13.9 micromol/L. The researchers point out that other studies have shown that omeprazole also lowers vitamin B12 levels and conclude that older people on long-term acid-suppressing drugs should be monitored for vitamin B12 deficiency and supplement if necessary.

Ruscin, J. Mark, et al. Vitamin B12 deficiency associated with histamine2-receptor antagonists and a proton-pump inhibitor. Annals of Pharmacotherapy, Vol. 36, May 2002, pp. 812-16

About Vitamin B12

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B12 is an important water-soluble vitamin. In contrast to other water-soluble vitamins it is not excreted quickly in the urine, but rather accumulates and is stored in the liver, kidney and other body tissues. As a result, a vitamin B12 deficiency may not manifest itself until after 5 or 6 years of a diet supplying inadequate amounts. Vitamin B12 functions as a methyl donor and works with folic acid in the synthesis of DNA and red blood cells and is vitally important in maintaining the health of the insulation sheath (myelin sheath) that surrounds nerve cells. The classical vitamin B12 deficiency disease is pernicious anemia, a serious disease characterized by large, immature red blood cells. It is now clear though, that a vitamin B12 deficiency can have serious consequences long before anemia is evident. The normal blood level of vitamin B12 ranges between 200 and 600 picogram/milliliter (148-443 picomol/liter).

A deficiency often manifests itself first in the development of neurological dysfunction that is almost indistinguishable from senile dementia and Alzheimer’s disease. There is little question that many patients exhibiting symptoms of Alzheimer’s actually suffer from a vitamin B12 deficiency. Their symptoms are totally reversible through effective supplementation. A low level of vitamin B12 has also been associated with asthma, depression, AIDS, multiple sclerosis, tinnitus, diabetic neuropathy and low sperm counts. Clearly, it is very important to maintain adequate body stores of this crucial vitamin.

Vitamin B12 is not absorbed very well so much larger amounts need to be supplied, through the diet or supplementation. The richest dietary sources of vitamin B12 are liver, especially lamb’s liver, and kidneys. Eggs, cheese and some species of fish also supply small amounts, but vegetables and fruits are very poor sources. Several surveys have shown that most strict, long-term vegetarians are vitamin B12 deficient. Many elderly people are also deficient because their production of the intrinsic factor needed to absorb the vitamin from the small intestine decline rapidly with age.

Helicobacter pylori and vitamin B12 deficiency

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ANKARA, TURKEY. It is estimated that more than 50 per cent of adults in developed countries are infected with the Helicobacter pylori bacterium. H pylori has been implicated in stomach ulcers, indigestion (dyspepsia), gastritis (inflammation of the stomach lining), stomach cancer, and MALT lymphoma. About 10-15 per cent of adults over 60 years of age are affected by a vitamin B12 (cobalamin) deficiency. Researchers at the Turkish Military Medical Academy now provide convincing evidence that the two are linked. A detailed study of 138 patients with vitamin B12 deficiency and anaemia discovered that 77 (58 per cent) of the patients had a H pylori infection. Eradication of this infection successfully cured the anaemia and reversed the vitamin B12 deficiency in 31 (40 per cent) of the 77 infected patients. The researchers conclude that a H pylori infection can cause a vitamin B12 deficiency and that this deficiency, in many cases, can be totally eliminated by eradicating the infection. EDITOR’S NOTE: Memory loss, fatigue, and mental confusion are often the first indicators of a vitamin B12 deficiency.

Kaptan, Kursad, et al. Helicobacter pylori – Is it a novel causative agent in vitamin B12 deficiency? Archives of Internal Medicine, Vol. 160, May 8, 2000, pp. 1349-53

Stopeck, Alison. Links between Helicobacter pylori infection, cobalamin deficiency, and pernicious anaemia. Archives of Internal Medicine, Vol. 160, May 8, 2000, pp. 1229-30 (editorial)

A natural, healthy and compassionate diet

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To be truly healthful, a diet must be best not just for individuals in isolation but must allow all six billion people to thrive and achieve a sustainable coexistence with the many other species that form the ?living earth?. From this standpoint the natural adaptation for most (possibly all) humans in the modern world is a vegan diet. There is nothing natural about the abomination of modern factory farming and its attempt to reduce living, feeling beings to machines. In choosing to use fortified foods or B12 supplements, vegans are taking their B12 from the same source as every other animal on the planet ? micro-organisms ? without causing suffering to any sentient being or causing environmental damage.

Vegans using adequate amounts of fortified foods or B12 supplements are much less likely to suffer from B12 deficiency than the typical meat eater. The Institute of Medicine, in setting the US recommended intakes for B12 makes this very clear. ?Because 10 to 30 percent of older people may be unable to absorb naturally occurring vitamin B12, it is advisable for those older than 50 years to meet their RDA mainly by consuming foods fortified with vitamin B12 or a vitamin B12-containing supplement.? Vegans should take this advice about 50 years younger, to the benefit of both themselves and the animals. B12 need never be a problem for well-informed vegans.

Good information supports vegan health, pass it around.

Lessons from history

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B12 is an exceptional vitamin. It is required in smaller amounts than any other known vitamin. Ten micrograms of B12 spread over a day appears to supply as much as the body can use. In the absence of any apparent dietary supply, deficiency symptoms usually take five years or more to develop in adults, though some people experience problems within a year. A very small number of individuals with no obvious reliable source appear to avoid clinical deficiency symptoms for twenty years or more. B12 is the only vitamin that is not recognized as being reliably supplied from a varied wholefood, plant-based diet with plenty of fruit and vegetables, together with exposure to sun. Many herbivorous mammals, including cattle and sheep, absorb B12 produced by bacteria in their own digestive system. B12 is found to some extent in soil and plants. These observations have led some vegans to suggest that B12 was an issue requiring no special attention, or even an elaborate hoax. Others have proposed specific foods, including spirulina, nori, tempeh, and barley grass, as suitable non-animal sources of B12. Such claims have not stood the test of time.

In over 60 years of vegan experimentation only B12 fortified foods and B12 supplements have proven themselves as reliable sources of B12, capable of supporting optimal health. It is very important that all vegans ensure they have an adequate intake of B12, from fortified foods or supplements. This will benefit our health and help to attract others to veganism through our example.

Getting an adequate amount of B12

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National recommendations for B12 intakes vary significantly from country to country. The US recommended intake is 2.4 mcgs a day for ordinary adults rising to 2.8 mcgs for nursing mothers. The German recommendation is 3 mcgs a day. Recommended intakes are usually based on 50% absorption, as this is typical for small amounts from foods. To meet the US and German recommendations you need to obtain sufficient B12 to absorb 1.5 mcgs per day on average. This amount should be sufficient to avoid even the initial signs of inadequate B12 intake, such as slightly elevated homocysteine and MMA levels, in most people. Even slightly elevated homocysteine is associated with increased risk of many health problems including heart disease in adults, preeclampsia during pregnancy and neural tube defects in babies.

Achieving an adequate B12 intake is easy and there are several methods to suit individual preferences. Absorption of B12 varies from about 50%, if about 1 mcg or less is consumed, to about 0.5% for doses of 1000 mcgs (1 mg) or above. So the less frequently you consume B12, the higher the total amount needs to be to give the desired absorbed amount.

Frequent use of foods fortified with B12 so that about one microgram of B12 is consumed three times a day with a few hours in between will provide an adequate amount. Availability of fortified foods varies from country to country and amounts of B12 vary from brand to brand, so ensuring an adequate B12 supply from fortified foods requires some label reading and thought to work out an adequate pattern to suit individual tastes and local products.

Taking a B12 supplement containing ten mcgs or more daily provides a similar absorbed amount to consuming one mcg on three occasions through the day. This may be the most economical method as a single high potency tablet can be consumed bit by bit. 2000 mcgs of B12 consumed once a week would also provide an adequate intake. Any B12 supplement tablet should be chewed or allowed to dissolve in the mouth to enhance absorption. Tablets should be kept in an opaque container. As with any supplement it is prudent not to take more than is required for maximum benefit, so intakes above 5000 mcg per week should be avoided despite lack of evidence for toxicity from higher amounts.

All three options above should meet the needs of the vast majority of people with normal B12 metabolism. Individuals with impaired B12 absorption may find that the third method, 2000 mcg once a week, works best as it does not rely on normal intrinsic factor in the gut. There are other, very rare, metabolic defects that require completely different approaches to meeting B12 requirements. If you have any reason to suspect a serious health problem seek medical advice promptly.

B12 Deficit May Boost Risk of Birth Defects

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Women who are vegans and vegetarians most affected, study says

MONDAY, March 2 (HealthDay News) — Women who do not have enough vitamin B12 in their blood before and after conception have a greater chance of having a baby with brain or spinal cord defects, a new study says.

Most at risk may be vegans and vegetarians, since B12 is far more common in meat and animal-based foods, noted an American and Irish research team whose findings were published in the March issue of Pediatrics..

According to the study, women with low levels of B12 had at least 2.5 times the risk of giving birth to a child with these neural tube defects, which can lead to partial paralysis or even death, than women with the highest B12 levels.

“Vitamin B12 is essential for the functioning of the nervous system and for the production of red blood cells,” Dr. Duane Alexander, director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, said in a news release issued by its parent organization, the U.S. National Institutes of Health. “The results of this study suggest that women with low levels of B12 not only may risk health problems of their own, but also may increase the chance that their children may be born with a serious birth defect.”

Researchers analyzed blood collected during the early pregnancy stages of hundreds of women from Ireland, a country with a high rate of neural tube defects. Either the women had previously given birth to a baby with a neural tube defect or were known to be carrying babies with the disorder. Women with B12 concentrations below 250 ng/L before pregnancy had roughly three times the risk of having a child with a neural tube defect as those with higher B12 blood levels. Those women whose levels were less than 150 ng/L, which is considered B12 deficient, had five times the risk of women with higher levels.

The researchers used statistical techniques to focus solely on B12 levels and factor out the role of folic acid, a nutrient known to help prevent pregnant women from birthing babies with neural tube defects. The study authors noted that B12 and folate are jointly linked to several key biochemical reactions, but that a lack of either B12 or folate increased the risk of a neural tube defect.

While confirmation from other studies is needed, the authors suggested women should have vitamin B12 levels above 300 ng/L before becoming pregnant. Study co-author Dr. James L. Mills, a senior investigator in the NICHD division of epidemiology, statistics and prevention research, went further, recommending all women of childbearing age always consume the daily recommended amount of vitamin B12 and at least 400 micrograms of folic acid.

Low levels of vitamin B12 may increase risk for defects

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WASHINGTON, March 2 — Children born to women who have low blood levels of vitamin B12 shortly before and after conception may have an increased risk of a neural tube defect, a new study says.

Women with the lowest B12 levels had five times the risk of having a child with a neural tube defect compared to women with the highest B12 levels. Women who consume little or no meat or animal based foods were the most likely to have low B12 levels, according to the joint study by the U.S. National Institutes of Health (NIH), Trinity College Dublin, and the Health Research Board of Ireland.

“Vitamin B12 is essential for the functioning of the nervous system and for the production of red blood cells,” said Duane Alexander, director of the National Institute of Child Health and Human Development (NICHD).

Researchers have known that taking another nutrient, folic acid, during the weeks before and after conception can greatly reduce a woman’s chances of having a child with a neural tube defect. Folic acid, which is the synthetic form of vitamin B. Neural tube defects, is a class of birth defects affecting the brain and spinal cord.

In the United States, cereal grains are fortified with folic acid to reduce the occurrence of neural tube defects in the U.S. population. Ireland has a high rate of neural tube defects, and NIH scientists have frequently collaborated with Irish researchers to gain insight into the causes of this group of disorders.

“The results of this study suggest that women with low levels of B12 not only may risk health problems of their own, but also may increase the chance that their children may be born with a serious birth defect.” Alexander said. The study appears in the March issue of the U.S. journal of Pediatrics.

Symptoms of B12 deficiency

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Clinical deficiency can cause anaemia or nervous system damage. Most vegans consume enough B12 to avoid clinical deficiency. Two subgroups of vegans are at particular risk of B12 deficiency: long-term vegans who avoid common fortified foods (such as raw food vegans or macrobiotic vegans) and breastfed infants of vegan mothers whose own intake of B12 is low. In adults typical deficiency symptoms include loss of energy, tingling, numbness, reduced sensitivity to pain or pressure, blurred vision, abnormal gait, sore tongue, poor memory, confusion, hallucinations and personality changes. Often these symptoms develop gradually over several months to a year before being recognized as being due to B12 deficiency and they are usually reversible on administration of B12. There is however no entirely consistent and reliable set of symptoms and there are cases of permanent damage in adults from B12 deficiency. If you suspect a problem then get a skilled diagnosis from a medical practitioner as each of these symptoms can also be caused by problems other than B12 deficiency.

Infants typically show more rapid onset of symptoms than adults. B12 deficiency may lead to loss of energy and appetite and failure to thrive. If not promptly corrected this can progress to coma or death. Again there is no entirely consistent pattern of symptoms. Infants are more vulnerable to permanent damage than adults. Some make a full recovery, but others show retarded development.

The risk to these groups alone is reason enough to call on all vegans to give a consistent message as to the importance of B12 and to set a positive example. Every case of B12 deficiency in a vegan infant or an ill informed adult is a tragedy and brings veganism into disrepute.

Is there a vegan alternative to B12-fortified foods and supplements?

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If for any reason you choose not to use fortified foods or supplements you should recognize that you are carrying out a dangerous experiment – one that many have tried before with consistently low levels of success. If you are an adult who is neither breast-feeding an infant, pregnant nor seeking to become pregnant, and wish to test a potential B12 source that has not already been shown to be inadequate, then this can be a reasonable course of action with appropriate precautions. For your own protection, you should arrange to have your B12 status checked annually. If homocysteine or MMA is even modestly elevated then you are endangering your health if you persist.

If you are breast feeding an infant, pregnant or seeking to become pregnant or are an adult contemplating carrying out such an experiment on a child, then don?t take the risk. It is simply unjustifiable.

Claimed sources of B12 that have been shown through direct studies of vegans to be inadequate include human gut bacteria, spirulina, dried nori, barley grass and most other seaweeds. Several studies of raw food vegans have shown that raw food offers no special protection.

Reports that B12 has been measured in a food are not enough to qualify that food as a reliable B12 source. It is difficult to distinguish true B12 from analogues that can disrupt B12 metabolism. Even if true B12 is present in a food, it may be rendered ineffective if analogues are present in comparable amounts to the true B12. There is only one reliable test for a B12 source ? does it consistently prevent and correct deficiency? Anyone proposing a particular food as a B12 source should be challenged to present such evidence.

Vitamin B12 Key to Aging Brain

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Deficiency led to more brain shrinkage, study shows

(HealthDay News) — Older individuals with low levels of vitamin B12 seem to be at increased risk of having brain atrophy or shrinkage, new research suggests.

Brain atrophy is associated with Alzheimer’s disease and impaired cognitive function.

Although the study, published in the Sept. 8 issue of Neurology, can’t confirm that lower levels of B12 actually cause brain atrophy, they do suggest that “we ought to be more aware of our B12 status, especially people who are vulnerable to B12 deficiency [elderly, vegetarians, pregnant and lactating women, infants], and take steps to maintain it by eating a balanced and varied diet,” said study co-author Anna Vogiatzoglou, a registered dietician and doctoral candidate in the department of physiology, anatomy and genetics at the University of Oxford, in England.

“It’s worth looking at B12 levels. It’s a simple blood test,” affirmed Dr. Shari Midoneck, an internist at the Iris Cantor Women’s Health Center in New York City. “It doesn’t hurt to take B12.”

Good sources of the vitamin include meat, fish, milk and fortified cereals.

According to the study authors, vitamin B12 deficiency is a public health problem, especially among older people.

This study involved 107 volunteers aged 61 to 87 who were cognitively normal at the beginning of the study. All participants underwent annual clinical exams, MRI scans and cognitive tests and had blood samples taken.

Individuals with lower vitamin B12 levels at the start of the study had a greater decrease in brain volume. Those with the lowest B12 levels had a sixfold greater rate of brain volume loss compared with those who had the highest levels of the vitamin.

Interestingly, none of the participants were deficient in vitamin B12, they just had low levels within a normal range.

“They all had normal B12 levels, yet there was a difference between the higher levels and the lower levels in terms of brain shrinkage, which is new information which could potentially change what we recommend to people in terms of diet,” said Dr. Jonathan Friedman, an associate professor of surgery and neuroscience and experimental therapeutics at Texas A&M Health Science Center College of Medicine and associate dean of the College of Medicine, Bryan-College Station campus.

Other risk factors for brain atrophy include high blood pressure, diabetes and high cholesterol.

Not only might B12 levels be a modifiable risk factor for cognitive decline, it might also be a clue to help clinicians assess cognitive problems earlier on. Right now, it’s not clear what the biological mechanisms behind the link might be, nor is it clear whether added B12 would avert brain atrophy.

“We are doing a clinical trial in Oxford in which we are giving B vitamins [including B12] to elderly people with memory impairment,” Vogiatzoglou said. “In this trial, we are doing MRI scans at the start and the end, and so, we will be able to find out if taking B vitamins really does slow down the shrinking of the brain. The trial will be completed in 2009.”

Testing B12 status

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A blood B12 level measurement is a very unreliable test for vegans, particularly for vegans using any form of algae. Algae and some other plant foods contain B12-analogues (false B12) that can imitate true B12 in blood tests while actually interfering with B12 metabolism. Blood counts are also unreliable as high folate intakes suppress the anaemia symptoms of B12 deficiency that can be detected by blood counts. Blood homocysteine testing is more reliable, with levels less than 10 mmol/litre being desirable. The most specific test for B12 status is methylmalonic acid (MMA) testing. If this is in the normal range in blood (<370 nmol/L) or urine (less than 4 mg /mg creatinine) then your body has enough B12. Many doctors still rely on blood B12 levels and blood counts. These are not adequate, especially in vegans.

Vitamin B12 deficiency common among elderly people

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NEW YORK, NY. Researchers at Columbia University have confirmed that elderly people often suffer from a lack of vitamin B12 (cobalamin). The deficiency is usually only discovered when patients develop megaloblastic anaemia. However, before this stage is reached, cobalamin-deficient individuals may develop neuropsychiatric damage and show signs of disorientation and confusion. The researchers evaluated 548 men and women aged 67 to 96 years and compared their cobalamin and folate status to that of 117 healthy, younger control subjects. They found that 40.5 per cent of the elderly people suffered from a vitamin B12 deficiency versus only 17.9 per cent in the younger group. There was no significant difference in folate status between the two groups. The researchers also found that people who took oral supplements containing vitamin B12 and folate (6 micrograms and 400 micrograms per day respectively) were much less likely to suffer from a deficiency than were people who did not supplement. They point out that as people age they become less and less able to absorb vitamin B12 from food and therefore are likely to develop a deficiency. As gastric atrophy progresses vitamin B12 status can only be maintained by taking high oral doses of cobalamin (500-1000 micrograms daily) or by routine intramuscular injections providing 1 mg per month. The researchers also point out that a vitamin B12 deficiency leads to an accumulation of homocysteine in the blood. An increased serum concentration of homocysteine and its derivatives is now recognized as a major risk factor in heart disease and stroke.

Lindenbaum, John, et al. Prevalence of cobalamin deficiency in the Framingham elderly population. American Journal of Clinical Nutrition, Vol. 60, July 1994, pp. 2-11
Allen, Lindsay H. and Casterline, Jennifer. Vitamin B12 deficiency in elderly individuals: diagnosis and requirements. American Journal of Clinical Nutrition, Vol. 60, July 1994, pp. 12-14

An Open Letter from Health Professionals and Vegan Organizations

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What Every Vegan Should Know about Vitamin B12

Very low B12 intakes can cause anemia and nervous system damage. The only reliable vegan sources of B12 are foods fortified with B12 (including some plant milks, some soy products and some breakfast cereals) and B12 supplements. Vitamin B12, whether in supplements, fortified foods, or animal products, comes from micro-organisms. Most vegans consume enough B12 to avoid anaemia and nervous system damage, but many do not get enough to minimize potential risk of heart disease or pregnancy complications.

To get the full benefit of a vegan diet, vegans should do one of the following:

eat fortified foods two or three times a day to get at least three micrograms (mcg or mg) of B12 a day or
take one B12 supplement daily providing at least 10 micrograms or
take a weekly B12 supplement providing at least 2000 micrograms.

If relying on fortified foods, check the labels carefully to make sure you are getting enough B12. For example, if a fortified plant milk contains 1 microgram of B12 per serving then consuming three servings a day will provide adequate vitamin B12. Others may find the use of B12 supplements more convenient and economical.

The less frequently you obtain B12 the more B12 you need to take, as B12 is best absorbed in small amounts. The recommendations above take full account of this. There is no harm in exceeding the recommended amounts or combining more than one option.

Good information supports vegan health, pass it around.

If you don?t read another word about B12, you already know all you need to know. If you want to know more, read on.

This information sheet was prepared by Stephen Walsh, a UK Vegan Society trustee, and other members of the International Vegetarian Union science group (IVU-SCI), in October 2001.

Vitamin B12 and Vegan Diets

Vitamin B12 deficiency linked to neuropsychiatric abnormalities

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KINGSTON, CANADA. Dr. Dianne Delva, MD, Assistant Professor of Family Medicine at Kingston University, reviews the evidence for and against routine supplementation with vitamin B12 (cobalamin) in the elderly. Several studies have shown that anywhere from 5 to 15 per cent of elderly people suffer from a vitamin B12 deficiency. Although the only formally recognized disorder linked to a cobalamin deficiency is megaloblastic anaemia, it is now becoming clear that many neurological and psychiatric symptoms may also be caused by a vitamin B12 deficiency. Ataxia (shaky movements and unsteady gait), muscle weakness, spasticity, incontinence, hypotension, vision problems, dementia, psychoses, and mood disturbances are but a few of the disorders which have recently been linked to possible vitamin B12 deficiencies. Dr. Delva points out that these disorders may occur at vitamin B12 levels just slightly lower than normal and considerably above the levels normally associated with anaemia. She also cautions that the blood level of cobalamin is an unreliable indicator of deficiency and that tissue levels of the vitamin may be quite low even though the blood levels are normal. The best test of cobalamin deficiency involves measuring the blood levels of homocysteine and methylmalonic acid. If the level of these two precursors to the metabolic reactions controlled by cobalamin are high then the vitamin B12 level is low. Vitamin B12 deficiencies may be treated by injections of the vitamin or by oral supplementation. Oral supplementation is just as effective as injections in most people and a lot less expensive. An oral dose of 100-250 micrograms/day is usually adequate although patients with absorption difficulties may need 1000 micrograms/day. Cobalamin has no known toxic effects.

Delva, M. Dianne. Vitamin B12 replacement – To B12 or not to B12? Canadian Family Physician, Vol. 43, May 1997, pp. 917-22

Diabetes drug linked to vitamin B12 deficiency

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A Wisconsin doctor reports a case of a 63-year-old man who developed a severe vitamin-B12 deficiency after having taken metformin (Glucophage) for five years. Replacing the metformin with sulfonylurea and taking 1000 mg of cyanocobalamin (vitamin B12) for two months reversed the deficiency. Dr. Mary Ann Gilligan estimates that 10 to 30 per cent of patients on metformin develop a vitamin B12 deficiency and points out there is some evidence that calcium supplementation will prevent it.

Archives of Internal Medicine, Vol. 162, February 25, 2002, pp. 484-85

Vitamin B12 deficiency and breast cancer

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BALTIMORE, MARYLAND. Researchers at the Johns Hopkins University report that women with breast cancer tend to have lower vitamin B12 levels in their blood serum than do women without breast cancer. The researchers determined vitamin B12 concentrations in blood samples obtained in 1974 and in 1989 and compared the levels found in 195 women who later developed breast cancer with the levels found in 195 women free of cancer. They found that postmenopausal women with the lowest serum levels of vitamin B12 had a 2.5-4.0 times greater likelihood of being in the breast cancer group than did women with the highest levels. The researchers found no correlation between breast cancer risk and serum levels of folic acid, vitamin B6, and homocysteine.

In a subsequent review of the findings Dr. Sang-Woon Choi, MD of Tufts University points out that serum levels of folate are a poor indicator of levels in tissues and that it may well be that there is a correlation between folate levels in breast tissue and breast cancer risk. Dr. Choi speculates that a vitamin B12 deficiency may lead to breast cancer because it could result in less folate being available to ensure proper DNA replication and repair.

Wu, K., et al. A prospective study of folate, B12, and pyridoxal 5′-phosphate (B6) and breast cancer. Cancer Epidemiol. Biomarkers Prev., Vol. 8, March 1999, pp. 209-17
Choi, Sang-Woon. Vitamin B12 deficiency: a new risk factor for breast cancer? Nutrition Reviews, Vol. 57, August 1999, pp. 250-60

Vitamin B12 deficiency common in older people

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MOLNLYCKE, SWEDEN. Swedish researchers have discovered that many older people are deficient in vitamin B12. Their study involved 368 men and women aged 75 years or older. Analysis of blood serum showed that 11 per cent of the participants were deficient in cobalamin (vitamin B12). The researchers point out that a vitamin B12 deficiency has been linked to neuropsychiatric disorders such as memory loss and dementia. The researchers discovered several cases of gastritis (inflammation of the lining of the stomach) and two cases of celiac disease among patients with low serum values of cobalamin. They conclude that routine screening for a vitamin B12 deficiency is justified in the case of older people.

In a separate letter to the Journal of the American Geriatrics Society doctors from the Union Memorial Hospital in Baltimore report on a case of vitamin B12 deficiency. The patient, an 85-year-old man, had developed progressive memory loss and lethargy over a two-year period. Although his serum level of vitamin B12 was within the currently accepted range, the doctors decided to proceed with vitamin B12 therapy. The patient received an intramuscular injection of 1000 micrograms of vitamin B12 for three consecutive days, then 1000 micrograms weekly for a month, and then one injection every month. By the fifth injection his mental status had vastly improved and his lethargy had completely vanished. The doctors conclude that the levels of serum vitamin B12 concentrations currently considered normal in the United States may be too low and should be reassessed. The lower limit of 200 pg/mL is based on the level that causes abnormalities in the blood (pernicious anaemia). In contrast the lower limit in Japan and some European countries is 500-550 pg/mL and is based on the level that causes mental manifestations such as dementia and memory loss. The doctors suggest that a trial of vitamin B12 therapy is warranted in patients with borderline cobalamin serum levels as it is effective and inexpensive.

Eggersten, Robert, et al. Prevalence and diagnosis of cobalamin deficiency in older people. Journal of the American Geriatrics Society, Vol. 44, No. 10, October 1996, pp. 1273-74
Goodman, Mark, et al. Are U.S. lower normal B12 limits too low? Journal of the American Geriatrics Society, Vol. 44, No. 10, October 1996, pp. 1274-75