Why B12 & Folinic Acid for Down syndrome?

Studies have shown that there is a tendency in Down syndrome to have low levels of B12 and Folinic (or Folic) Acid. Supplementing with B12 and Folinic Acid helps to normalize metabolism. Folic Acid is particularly important in the population of people with Down syndrome. It is needed for the synthesis of DNA and RNA, which are the building blocks of cells. Folic Acid also helps prevent changes to the DNA that could lead to cancer. It is also needed in both children and adults to be able to make normal red blood cells and prevent anemia. Specifically, B12 and Folinic Acid are used in a metabolic cycle called the SAM cycle.

Please visit Changing Minds Foundation's page on B12 and Down syndrome for more details. http://www.changingmindsfoundation.org/documents/b12_folinic_acid.html

Dosage

B12
Birth to 2 years: 200-400mcg
Children 2- 12 years old: 400-1000mcg
Teen/Adults: 1000-2000mcg

Folinic Acid
Birth to 2 years: 200 mcg
Children 2- 12 years old: 400-800 mcg
Teen/Adults: 800-2000 mcg

Products I use for Jett

Different children need different forms of B12. Some can't tolerate methylcobalamin, otherwise, it's the best form to use.
B12 http://www.vitacost.com/NSI-Vitamin-B-12-Methylcobalamin-Raspberry-Flavor

The folinic acid can't be folic acid or folate.
Folinic Acid http://www.iherb.com/Metagenics-FolaPro-120-Tablets/20940?at=0

This is the best over the counter choice, but see if your doctor will prescribe Deplin {folinic acid} since it's more potent.

Articles

Brain Takes Multiple Hits from Low B12 Levels
By Crystal Phend, Senior Staff Writer, MedPage Today

Published: September 26, 2011
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
Low levels of vitamin B12 may contribute to cognitive problems for older adults in more than one way, according to a cross-sectional study.

Markers of B12 insufficiency all predicted lower global cognitive scores over nearly five years of follow-up, Christine C. Tangney, PhD, of Rush University Medical Center in Chicago, and colleagues found.

The mediating factors appeared to be white matter lesions and cerebral infarcts in association with the nonspecific marker homocysteine and brain atrophy for the vitamin B12-specific marker methylmalonic acid (MMA).

"Vitamin B12 status may affect the brain through multiple mechanisms," the group wrote in the Sept. 27 issue of Neurology.

Note that previous studies have suggested that poor vitamin B12 status may be a risk factor for brain atrophy and possibly cognitive impairment.

Note that in this study, concentrations of vitamin B12–related markers (methylmalonate, cystathionine, homocysteine) were associated with global cognitive function and with total brain volume.

The Institute of Medicine already recommends B12 supplements for seniors, co-author Martha Clare Morris, ScD, director of nutrition at Rush University Medical Center, noted in an interview with MedPage Today.

"Insufficient vitamin B12 is very common in older people," she explained. "The older we get we have a decreased ability to absorb vitamin B12 from our diet. ... Medications can also impair absorption."

But middle age adults may be another important population for screening and possible supplementation, Morris suggested.

Although her group's observational study couldn't say whether boosting B12 would prevent or reverse cognitive effects, a prior randomized trial demonstrated that high-dose B complex supplements could slow down brain atrophy in older adults.

In that study, dubbed VITACOG, supplements did a better job of holding cognitive declines at bay than placebo among those with high homocysteine levels.

"So at least from this one clinical trial it appears that [supplementation] may have some benefit," Morris argued.

Her group dug deeper into their Chicago Health and Aging Project (CHAP), measuring vitamin B12-related markers in relation to brain MRI and neuropsychological test results 4.6 years later in 121 residents of Chicago's South Side, ages 65 and older.

After adjustment for age, sex, education, race, and serum creatinine levels to control for renal function problems that could have an impact on homocysteine, all of the B12-related markers affected global cognitive scores.

The estimated effect from each 1 µmol/L higher concentration of a marker ranged from 0.001 to 0.03 standardized units of lower global cognitive score for MMA (P=0.02) and homocysteine (P=0.04).

Higher levels of individual markers were related to lower performance on various cognitive domains:

For homocysteine, trends for perceptual organization and speed
For cystathionine and 2-methylcitric acid, significant impacts on episodic memory and poor semantic memory
For MMA, significantly worse episodic memory and perceptual speed

Each of the markers also predicted decreased total brain volume at higher levels.

Homocysteine also correlated with white matter hyperintensity volume at 0.103-units more of this cerebrovascular risk marker per µmol/L (P=0.009).

This impact on white matter hyperintensity volume appeared to partly explain homocysteine's effect on global cognitive function.

Cerebral infarcts also appeared to be playing a role as adjustment for the two factors equally attenuated the association between homocysteine and global cognitive score down to a P=0.08 level of significance.

Total brain volume, though, appeared to be mediating the other B12 insufficiency markers' effects on global cognition, as adjustment for brain size attenuated away the links with MMA, cystathionine, and 2-methylcitric acid.

Notably, no measures on MRI or cognitive testing linked directly to serum B12 levels.

Although clinical screening typically relies on serum B12, Morris warned that this may not give a full picture of whether the effects of insufficiency are accumulating.

"You might be in the normal range, say in the low normal range, of vitamin B12 in your blood but still have evidence of insufficient vitamin B12 based on these biomarkers," she told MedPage Today.

The researchers cautioned that lack of serial MRI and measurements prevented any conclusions on whether poor vitamin B12 status speeds up brain atrophy and demyelination.

Another limitation was the lack of data on serum folate and vitamin B6, they added.

The study was supported by the National Institute on Aging.

Tangney reported receiving research support from the National Insitute on Aging.

Morris reported receiving research support from the U.S. Department of Health and Human Services, the National Institute on Aging, the Abbott Fund, and the Sprague Institute.

Coauthors reported sitting on scientific advisory boards for Pfizer; consulting for Pain Therapeutics, Bayer Schering Pharma, and Avanir Pharmaceuticals; and serving on a data safety monitoring committee for Eli Lilly.

Primary source: Neurology
Source reference:
Tangney CC, et al "Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination" Neurology 2011; 77: 1276–1282.

Related Posts

Folic Acid Cut Alzheimer's Risk by Half

Alzheimer's Disease & Down syndrome

Jett's Supplement List

Thyroid & DS Go Hand in Hand

Which Multivitamin?

Anemia Causes & Cures

Natural Ways to Help with ADD

Natural Ways to Help with ADD & Hyperactivity

This is an adaption by Kay Ness from the Willis list.

There are eight things that reverse inattention and hyperactivity every time.

A 2003 study listed these causes:

1. Food and additive allergies
2. Environmental toxicity
3. Dietary deficiencies of protein
4. Excess of simple sugars
5. Mineral imbalances, particularly iron deficiency
6. Deficiencies in cell membrane components (Fatty acids and Phospholipids)
7. Thyroid disorders
8. Deficiencies in B-vitamins

What to do:

First: NO sugar, fruit juices, aspartame (NutraSweet), Splenda, MSG, and limited and controlled amounts of High-Glycemic Indexed foods.

Second: NO Phosphates (meaning processed meats, soft drinks, prepared cakes and baked goods with phosphates/phosphoric acid or bromine added).

Third: eliminate all allergens.

Fourth: NO colors, dyes, or high salicylate foods (Feingold diet).

These four cost nothing, yet often solve the problem.

Fifth: supplement 100 mg Vitamin B6 (with 50 mg vitamin B2) both 3 times a day. This alone has proven more effective than Ritalin, with no side effects.

Sixth: supplement 50 mg zinc (at evening on empty stomach with a little oil) and supplement 100 mg magnesium 3 times a day. Always supplement 50 mg vitamin B1 three times a day with the magnesium.

Seventh: Introduce fatty acids into the diet: Evening Primrose Oil and cod-liver oil (DHA alone
will not work).

Eighth: Underneath all this place a good multivitamin/mineral.

Other supplements known to help with the hyperness are calcium, iron, chromium, boron, lithium orotate, folic acid, glutathione, the amino acid tyrosine (builds dopamine and the stimulating hormone norepinephrine), taurine and *GABA (calming amino acids), and Saccharomyces boulardii and colostrum to build Immunoglobulin-A (IgA) to overcome allergies.

Children with blood lead levels above 10 micrograms per deciliter were nearly three times as likely to show hyperactivity and anti-social behavior as children whose blood lead levels were between 0 and 2 micrograms per deciliter. Detoxifying lead naturally.

Kay says she'd add magnesium to the mix.
Chembalance.com addresses minerals and specific vitamin deficiencies that you can test yourself every day. Oh, I'd also look at iodine. I don't believe the 'every time' thing but certainly this is a good and basic list.

*Since DS causes an overexpression of GABA, I wouldn't supplement our kids with it, unless you know specifically that your child needs it. -Andi

Another article on treating ADD naturally found here: http://intelegen.com/nutrients/add.htm

ADD & ADHD

ADD & ADHD Natural Control of ADD & ADHD
Billie J. Sahley, Ph.D., CNC

In Toxic Psychiatry, Peter Breggin, MD states, Hyperactivity is the most frequent justification for drugging children. Difficult-to-control children are certainly not a new phenomenon, but attempts to give them a medical diagnosis are the product of modern psychology and psychiatry. At first, psychiatrists called hyperactivity a brain disease: minimal brain dysfunction (MBD). When no minimal brain dysfunction could be demonstrated, the label became attention deficit disorder (ADD).

Six million children in this country suffer some type of learning disability, ADD, or ADD with hyperactivity (ADHD). Over two million children currently take Ritalin for ADD/ADHD. ADD and ADHD may be caused by psychological problems, including trauma and abuse, nutritional deficiencies, chemical imbalances, allergic responses to food and chemicals, or a poor diet. A failure in the brains inhibitory system (the ability of the brain to inhibit and control itself) may also cause ADD/ADHD.

Ritalin, the most commonly used drug for ADD and ADHD, is an amphetamine and a Schedule II class drug (other Schedule II drugs are morphine, opium, and medicinal cocaine). Doctors prescribe Ritalin for many children who do not need it, causing a number of adverse mental and physical side effects. Yet this potent, toxic drug is being used as a quick fix to quiet children. Surprisingly, prescription rates for Ritalin doubled between 1992 and 1996.

Children demonstrating symptoms of anxiety, ADHD or ADD often have an imbalance in their brains biochemistry. A biochemical imbalance results from a deficiency of neurotransmitters, the chemical messengers of the brain. If a biochemical imbalance goes untreated, a child can display maladaptive behavior, followed by possible long-term physical and emotional problems.

A childs state of health reflects his or her state of nutrition. When minerals, vitamins, amino acids, enzymes, or even hormones are deficient in a childs system, the result can be a disturbed biochemical homeostasis causing impaired functions in the brain. This, in turn, can cause an inability to focus, concentrate, and stay on task.

At the Pain and Stress Center in San Antonio, we have successfully treated numerous children with orthomolecular therapy. Orthomolecular therapy corrects the brains biochemical imbalance, without toxic drugs that can produce adverse side effects. ADD/ADHD presents a major problem facing parents today. Most people think of hyperactivity as some type of behavioral problem (a child who is impatient, impulsive, and constantly moving); but not all hyperactive children are aggressive. Some are very passive, withdrawn, and find it hard to communicate their feelings.

ADD/ADHD is not a condition that can be measured in precise scientific terms. Nor is it a situation with a quick fix, especially with powerful and addictive drugs such as Ritalin. ADD/ADHD is a complex and intricate condition in which children demonstrate maladaptive or disorganized behaviors, which put them out of sync with the world around them.

Numerous clinical studies established that hyperactive children often have low serotonin levels. A proper combination of tryptophan or 5-HTP and B6, elevates the serotonin level and balances the brain; the childs symptoms diminish. The dosage, of course, depends on the childs age, weight, and the degree of hyperactivity.

Effectiveness of Amino Acids
Neurotransmitters affect behavior and learning. A neurotransmitter deficiency consequently has a dramatic effect on childrens or adults abilities to learn and function in an orderly manner. Most hyperactive and ADD children are born with a shortage of neurotransmitters, establishing a genetic link, most often on the male side. These children also do not manufacture the needed amount of these chemical messengers.

Where do we get neurotransmitters? From the amino acids, GABA, glycine, taurine, tyrosine, glutamine and tryptophan. Do children or adults get enough aminos through diet? NO! Balanced amino-acid doses, in the right combination and formulas, produce the needed neurotransmitters naturally. Using a stimulant medication to try to produce neurotransmitters is like a shotgun going off in the childs brain. Our children were not born with Ritalin in their brain, so how can they have a Ritalin deficiency?

Approximately fifty different neurotransmitters exist in the human brain, but communication between brain cells uses only ten (approximately) major neurotransmitters. How we feed the brain directly affects our production of neurotransmitters. With proper nutrition and supplementation, we can correct or enhance mind, mood, memory, and behavior.

All major neurotransmitters are made from amino acids and dietary protein. One of the dangers of a low-protein diet is not ingesting enough amino acids to make adequate brain neurotransmitters. Apathy, lethargy, difficulty concentrating, loss of interest, and insomnia all result when the diet does not include adequate amounts of amino acids. Drugs do not produce or increase production of neurotransmitters. Drugs only address symptoms. Amino acids restore the balance nature intended.

Some of the major symptoms of neurotransmitter deficiencies are ADD, ADHD, brain fog, mood swings, increased stress, anxiety, depression, insomnia, irritability, and aggression. Stress plays a major role in the depletion of neurotransmitters. Inhibitory neurotransmitters are the keys to behavior, emotions, and pain. Inhibitory amino acids include tryptophan, taurine, GABA, and glycine.

Millions of people have turned to drugs known as SSRIs (Selective Serotonin Reuptake Inhibitors). These drugs, such as Prozac, Paxil, Zoloft, and Effexor work by selective enhancement of serotonin levels. SSRIs prevent the presynaptic nerve from reabsorbing serotonin that it previously secreted. Prozac causes an increase in brain serotonin levels; but Prozac and other prescription drugs do not increase neurotransmitters. (See Figure 1).

5-HTP is synergistic with other supplements that enhance neurotransmitters such as GABA, glutamine, tyrosine, phenylalanine, and glycine. Magnesium prolongs the benefits of 5-HTP. Chronic stress depletes available serotonin, as well as interferes with serotonins ability to control behavior. Research demonstrates that low serotonin levels can change brain function and impair learning. Low serotonin may be responsible for an increase in depression and drug use among teens and children. Most teens with low serotonin levels are more prone to try recreational drugs or even prescription drugs, for relief. A low brain serotonin level impairs the ability to focus and reason. 5-HTP shows a lot of promise as a natural answer to a multitude of problems that plague adults and children. Use caution with 5-HTP if your child is taking prescription antidepressant medications.

GABA (Gamma-aminobutyric acid)
GABA, an inhibitory neurotransmitter, is found throughout the central nervous system. GABA assumes an ever-enlarging role as a significant influence on ADD, ADHD, stress, anxiety, and depression, as well as stress-induced illnesses. According to Candace Pert, a neuroscientist who discovered the GABA receptor, every cell in the body has a GABA receptor, which is one reason why GABA has such positive effects. GABA inhibits the cells from firing, diminishing anxiety-related messages.

Tranquilizers provide only temporary relief. We have seen many patients on Xanax that still experience anxiety. They have been told it is not addictive: it is! THERE IS NO SUCH THING AS A TRANQUILIZER DEFICIENCY! Nutrient deficiencies do occur, however; and they can and do change behavior. GABA, glutamine, and glycine prove vital for energy and the smooth running of brain functions. We have successfully used these three amino acids with patients to ease anxiety, irritability, and ADD.

Research demonstrates a large number of children who display ADD/ADHD behavior actually experience anxiety. If they use all available GABA, then the receptors in the brain become empty, allowing the brain to be bombarded with random firings of excitatory messages. However, when adequate amounts of GABA are present, the reception of multiple random firings are blocked, so the brain does not become overwhelmed. At the Pain & Stress Center we regularly combine GABA and other amino acids to achieve positive results. Dose amounts vary, depending on the age and weight of the child.

GABA now takes its place as a major influence on those taking drugs, and in many cases, replacing the drugs. We have found that, when combined with other amino acids, GABA works exceptionally well with ADD children.

L-Glutamine
Glutamine, along with GABA and Glycine, is rapidly becoming an important therapeutic amino acid of the 21st century. Glutamine, found in many foods, is the third most abundant amino acid in the blood and brain. It also provides a major alternative fuel source for the brain when blood sugar levels are low.

Glutamine functions as an inhibitory neurotransmitter, and is the precursor for GABA, the antianxiety amino acid. The amino acid trio of Glutamine, GABA, and Glycine plus B6 are among the major inhibitory neurotransmitters in the brain. Glutamine is found in the nerves of the hippocampus, the memory center of the brain, in the cranial nerves, and in many other areas of the brain. These three amino acids work together as inhibitory neurotransmitters. Anyone taking amino acids must take B6 to metabolize the amino acids.

Intellectually impaired children and adults often show an increase in IQ after taking glutamine in combination with Ginkgo biloba and B6. Dr. Roger Williams demonstrated that children and adults diagnosed with ADHD showed a marked improvement when taking 250 mg to 1,000 mg of glutamine daily.

GABA and glutamine are not only found in the brain, but also in the receptor sites throughout the body. Glutamine is the memory and concentration amino acid. Seventy five percent of hyperactive and ADD childrens blood tests showed low levels of glutamine.

Dr. C. Fredericks research also demonstrated a definite increase in the IQs of children given glutamine. When glutamine was given daily, children showed impressive improvements in their abilities to learn, to retain, and to recall. Glutamine is a major part of my orthomolecular program for hyperactive and ADHD children. Glutamine is one of the amino acids that create the neurotransmitters in the brain that enhance learning and memory. Hyperactive and ADD children have low neurotransmitter levels, especially glutamine. Adding glutamine increases the level of neurotransmitters. Start with 500 mg of glutamine and gradually increase until you reach the optimal dose for your child, to a maximum of 3,000 mg per day.

Taurine
Taurine is now classified as a conditionally essential amino acid in the adult. In infants and children, however, taurine is an essential amino acid. As one of the sulfur amino acids, adults synthesize taurine from cysteine and methionine, provided B6 and zinc are present. Taurine is found abundantly throughout the body in the heart, olfactory bulb, central nervous system, and brain (hippocampus and pineal gland).

As an inhibitory neurotransmitter, taurine, after GABA, is the second-most important inhibitory transmitter in the brain. Taurines inhibitory action in the brain equals that of GABA and glycine. Its inhibitory effect is one source of taurines anticonvulsant and antianxiety properties.

Some children with Downs syndrome have shown an increase in IQ levels when taurine was added to their diet along with glutamine, B6, and vitamin E. The need for taurine increases whenever you experience more stress than usual, or have an illness.

Tyrosine
Tyrosine is the amino acid and inhibitory neurotransmitter that often helps overcome depression. Clinical studies show that tyrosine controls medication-resistant depression.

In a 1980 issue of the American Journal of Psychiatry, a study by Dr. Alan Gelenberg of Harvard Medical School discussed the role of tyrosine in the control of anxiety and depression. Dr. Gelenberg postulated that the lack of available tyrosine results in deficiency of the hormone norepinephrine at a specific location in the brain that relates to mood problems such as depression. Children given tyrosine supplementation demonstrated a marked improvement in mental performance and mood stability.

Tyrosine, because of its role in assisting the body to cope physiologically with stress and building the bodys natural store of adrenaline, deserves to be called the stress amino acid. Stress exhaustion requires tyrosine. During periods of stress, in order to continue coping with stress physiologically, the brain requires tyrosine. Tyrosine aids children and young teens, as well as adults, with recurrent depression and mood disorders. In children, dosage ranges from 200 to 500 mg daily.

Glycine
Glycine is a nonessential amino acid, with the simplest structure of all the amino acids resembling glucose (blood sugar) and glycogen (excess sugar converted in the liver for storage). Glycine is sweet to the taste, can be used as a sweetener, and can mask bitterness and saltiness. Pure glycine dissolves readily in water. As the third major inhibitory neurotransmitter in the brain, glycine readily passes the blood-brain barrier. Studies by the late Carl Pfeiffer, MD, Ph.D., demonstrated glycine as an important factor in psychiatric disorders.

Glycine decreases the craving for sugar, and, in many cases, can replace sugar on foods such as cereal. Glycine calms aggression in both children and adults. When combined with GABA and glutamine, glycine influences brain function by slowing down anxiety-related messages from the limbic system.

As a very nontoxic amino acid, both children and adults can use glycine. Glycine can be mixed with other amino acids. Doses for a child range between 500 to 2,000 mg daily, divided.

Magnesium
Hyperactive or ADD children are almost always deficient in magnesium. Magnesium proves necessary for proper brain energy and is the first mineral depleted when anyone (child or adult) is under stress. Magnesium is a stress mineral, and deficiency can lead to hyperactive or ADD behavior.

Magnesium plays a significant role in sugar metabolism and in the proper utilization of carbohydrates to create energy. Magnesium is so very important in a childs diet, especially if he displays hyperactive behavior, ADD, or other behavioral problems. Magnesium can be taken in liquid form, tablet, or capsule.

When added to the ADD/ADHD diet, calming effects sometimes occur immediately. Most magnesium exists inside the cells where it activates enzymes necessary for the metabolism of carbohydrates and amino acids. In 1988, a study published in Alternative Medicine Review linked the development of ADHD to low blood-serum magnesium levels. A group of children followed for six months were given 200 mg of magnesium a day. Researchers noted remarkably decreased hyperactivity in the children.

As a major nutrient needed by ADD/ADHD children and adults, magnesium is the number one stress mineral needed by the body. Magnesium is responsible for over three hundred enzyme functions. It cannot be stored by the body, and it must be taken daily. Symptoms of magnesium deficiency include asthma, migraines, eye twitches, anxiety, confusion, muscle spasms, irritability, depression, nervousness, fatigue, mood swings, PMS, hypertension, and insomnia.

Calcium
A calcium deficiency can also induce ADD/ADHD behavior. A child deficient in calcium exhibits irritability, sleep disturbances, anger, and inattentiveness. The first signs of a calcium deficiency include nervous stomach, cramps, tingling in the arms and legs, and painful joints. A calcium deficiency can also lead to ADD/ADHD behavior. Children sensitive to dairy products must receive daily calcium supplementation in capsule, chewable, or liquid form. Children up to 10 years of age need 1000 mg of calcium daily; adolescents need 1,200 to 1,500 mg daily. For those involved in sports activities, calcium supplementation is a must.

Huperzine
Recent research reports that Huperzine A improves mental function and learning in adolescents. Chinese researchers designed a study to determine the efficiency of Huperzine on memory and learning. The clinical study included 34 matched pairs of junior middle school students that had significant complaints of poor memory and difficulty in learning. In the double blind trial, half of the students received a placebo while the other half received Huperzine A for four weeks. Academic performance was measured before and after the clinical trial. The Huperzine group scored significantly better on standard memory tests without side effects.

Huperzine A is an extract derived from Chinese club moss. Huperzine can be combined with amino acids and other nutrients. The suggested dosage is one 50 mcg capsule in the morning and in the evening for children aged 12 and over.

This information is excerpted from my book Control Hyperactivity/ADD Naturally. Other resources include Is Ritalin Necessary?

Both are available through:

Pain & Stress Center
5282 Medical Dr. #160
San Antonio, TX 78229-6023

Related Posts

Folic Acid Cut Alzheimer’s Risk in Half

September 7, 2005 by Jean Carper

If you want to keep your mind sharp and avoid Alzheimer’s as you get older, don’t forget to take your folic acid daily. It can slash your chances of Alzheimer’s in half, says new research.

Getting 400 micrograms or more of folic acid a day cuts your risk of developing Alzheimer’s an astonishing 55 %, according to a large new study from the Institute for Brain Aging and Dementia at the University of California at Irvine.

Folic acid appears more powerful than antioxidants, such as vitamin E, and other B vitamins in slowing brain aging, say researchers Maria Corrada and Dr. Claudia Kawas who studied the impact of several dietary factors on the risk of Alzheimer’s among 579 people age 60 and older who participated in the Baltimore Longitudinal Study of Aging.

Those who got high vitamin E and vitamin B6 also had lower rates of Alzheimer’s. But only folic acid was associated with a significantly decreased risk.

Corrado, an assistant professor of neurology, noted that most people who got the amounts of folic acid needed to cut Alzheimer’s risk dramatically took folic acid supplements. The dose in food alone was not enough.

A recent Dutch study also found that older people who took 800 mcg of folic acid daily slowed brain aging by 5 years, compared with those on a placebo, as measured by scores on memory tests. For example, someone age 60 who took 800 mcg of folic acid daily had the memory of someone age 55.

Folic acid also helped prevent toxic deposits of beta amyloid, a marker for Alzheimer’s, in the brains of lab animals in tests at the National Institute on Aging. One theory is that high homocysteine due to a lack of folic acid (and other B vitamins) may damage the DNA of brain cells, promoting beta amyloid accumulation, leading to cognitive decline and Alzheimer’s.

Source: Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, August, 2005)

To save your brain from decline as you age, be sure to get B vitamins, particularly folic acid.

That’s the message from two major new studies finding that older people with diets and blood levels low in B vitamins are more apt to suffer cognitive decline, dementia and Alzheimer’s disease. Such individuals are also more apt to have higher blood levels of homocysteine, a protein tied to heart disease and dementia. .

Of all B vitamins, folic acid is most potent in protecting the brain from the ravages of aging–such as memory loss, dementia and Alzheimer’s–according to the new studies–one from Tufts University and the other from the University of Bologna in Italy. Both have just been published in the September issue of The American Journal of Clinical Nutrition.

Italian researchers found that older men and women with low folate (folic acid) blood levels were nearly twice as apt to develop dementia and Alzheimer’s over a four-year period as those with higher blood folate.

Subjects with the least folic acid in their diets and blood also performed worst on a number of tests of memory and cognitive function in the Tufts study. Those low in B6 also scored poorly on the cognitive tests.

What’s the reason? Scientists have long speculated that B vitamins, mainly folic acid, protect the brain by reducing toxic levels of homocysteine in the blood. Some believe homocysteine directly damages brain cells and function.

However, for the first time, these two new studies say that folic acid has powers to protect the brain independently, regardless of its ability to suppress homocysteine levels.

Bottom line: Both low intake of folic acid and/ or high blood homocysteine, predict brain decline as you age.

---



Folinic vs. Folic Acid



http://www.tahomaclinic.com/folate.html



June 2010 Nutrition & Healing



Is the mainstream still cheating you out of the best health possible—with folic acid?!



Discover the stunning truth behind this essential “vitamin”—and the simple switch that’s much, much better for you



Do you remember a few years ago, when “mainstream” print and broadcast media were telling us that vitamin E was bad for our cardiovascular systems, and would increase our risk of heart attack? Turns out the whole thing was based on -you guessed it- researchers not copying Nature!



They weren’t using Nature’s own of vitamin E—a combination of alpha-, beta-, delta- and gamma-tocopherol, sometimes with alpha-, beta-, delta-, and gamma-tocotrienol—in the same percentages and combinations found in Nature. Instead, they had used alpha-tocopherol only in their research—and reported an increase in cardiovascular risk.



Fortunately, since then it has been pointed out that gamma-tocopherol is more important in protecting the heart than alpha-tocopherol. In fact, supplementing alpha-tocopherol alone depresses levels of gamma-tocopherol, so increased risk to the heart isn’t altogether surprising. What can we learn from this? It’s pretty obvious—using a natural substance in a way that goes against Nature’s perfect design can cause problems.



Given the news, responsible vitamin suppliers quickly replaced alpha-tocopherol-only forms of vitamin E with “mixed tocopherols,” combinations of alpha-, beta-, delta, and gamma-tocopherols.



In a similar turn of events, recently accumulating research has found that supplemental folic acid, incorrectly identified as a vitamin (it’s actually an oxidized vitamin) since its synthetic crystallization in the 1940s, may actually accelerate cognitive decline in some older individuals. It’s also being linked to increased risk of colon and rectal cancers, increased risk of childhood asthma born to folic-acid supplemented mothers, and accelerated growth of pre-existing cancers.



There’s enough research that Reader’s Digest magazine recently published an article warning readers about the dangers of too much folic acid. Unfortunately, the article showed that not only journalists, but even medical professionals still haven’t figured out that folic acid is not the same as the naturally occurring vitamin folate.



Six of one is NOT half a dozen of the other



According to the article, a university-affiliated medical doctor stated: “We’ve known for years that getting too little folate can promote cancer. Now it looks like getting too much folic acid could be harmful too.”



Like much of the medical mainstream, he used folic acid and folate as interchangeable terms.



But folic acid is not the same as folate!



Folic acid is a single type of molecule, crystallized in 1943 by a scientist working for the patent medicine company Lederle Laboratories, then a subsidiary of American Cyanamid Corporation. Folic acid is the fully oxidized form of naturally occurring folates, which are found in leafy and green vegetables such as spinach, asparagus, turnip greens, romaine, lettuce, broccoli, Brussels sprouts, and bok choy. Other sources include corn, beets, tomatoes, dried or fresh beans and peas, fortified sunflower seeds and some fruits, including oranges, grapefruit, pineapple, cantaloupe, honeydew melon, banana, raspberries, and strawberries. Liver (only organic, of course) and brewer’s and baker’s yeasts are good sources of folate, too.



But—and this is important to understanding the difference between folic acid and the various naturally occuring folates—none of these vegetables, fruits, liver or yeast naturally contain even one molecule of folic acid.



How the mainstream convinced us we need folic acid, and not folate



So why is folic acid so firmly entrenched in the public and mainstream professional mind as a vitamin? For the same reasons that mainstream professionals, science writers (who should know better), and the majority of the public think that horse estrogen and human estrogen are the same thing. It’s a combination of a sloppy understanding of biochemistry and some clever patent-medicine-company-

supported and -promoted psychology.



First, the biochemistry. (Stay with me, it’s relatively easy.) Folate was originally isolated from brewer’s yeast and spinach in the 1930s. Once isolated and exposed to air it becomes unstable and breaks down, and is generally no longer useful in nutrition. But a small amount of natural folate can be transformed by oxidation (a natural process) into folic acid, a much more stable form with a very long shelf life.



While human and animal cells cannot use the folic acid molecule itself in their normal metabolic processes, human cells (principally the liver) can transform folic acid back into many of its metabolically useful folate forms. That’s why folic acid—despite not being found in food—can do so much nutritional good, the best-known example being the prevention of birth defects including spina bifida, cleft lip, and cleft palate.



As we grow older, though, our bodies are increasingly slow at transforming folic acid into usefully metabolized folates. That’s probably why scientists are finding that folic acid (not folate) is associated with cognitive decline in the elderly. Some of these studies have shown significantly elevated levels of un-metabolized (and therefore not useful) folic acid building up in the bloodstreams of supplemented older individuals.



In addition to worsening folic acid metabolism with age, there are also a significant number (as high as 5 percent or more in some populations) of survivable human genetic defects of folate metabolism which make it more difficult or, in some circumstances, impossible for sufferers to make metabolic use of folic acid.



Now, the psychology. Imagine you’re the sales and marketing arm of a patent medicine company. Which would you rather produce and sell: A then-process-patentable substance (folic acid) or an un-patentable substance (folate)? A substance with a longer shelf life (folic acid), or a substance that breaks down very rapidly on exposure to heat, cold, or light—even from “just sitting there” (folate)? A substance that’s less expensive to manufacture and process (folic acid), or a more expensive substance (folate)? The answer is pretty obvious—from a marketing point of view, folic acid wins every time.



And in this case, by great good luck, folic acid does do some good. It can be re-metabolized into various metabolically useful forms in most people—particularly younger people. So of course folic acid is promoted as a vitamin—even though it’s not found naturally in food—and manufacturers happily encourage everyone to speak of it interchangeably with folate, just as the Wyeth company so successfully confused Premarin with human estrogen in the public mind.



As usual, the mainstream way does more harm than the natural way



So since the 1940s, when physicians wanted to give their patients supplemental folate, they were taught to start with folic acid under one or another brand name. Even I was taught that at the University of Michigan in the 1960s. Supplement companies have sold folic acid, too, as it appeared to do the job, and there were for years no reports of harm. In fact there was very little, if any, research into potential harm.



But now that there is enough evidence of potential harm from folic acid, it’s time for all of us who want the benefits to switch back to the forms of folate found in food, which our bodies can use more efficiently and effectively than folic acid. Of course, we should always start by eating as much folate-containing food as possible, and as fresh as possible, too.



Remember, naturally occurring folates break down quite rapidly with heat, cold, light, even when they’re still in the food. Because of this naturally rapid breakdown, even the most avid vegetable and fruit eaters often need folate supplementation. (For a simple way to find out if you’re among them, see “Overlooked blood test could be the key to your good health” below.) Fortunately, about a year or two ago, responsible supplement suppliers began to make individual folate (not folic acid) supplements available. Some suppliers have just started to include various forms of folate in multiple vitamins and other combinations.



So it’s time to make folic acid supplements a part of history, and use only forms of naturally occurring folate when we use supplements. A little bit of folic acid (100 to 200 micrograms, the amount found in many multiple vitamins at present) is not likely to be a problem, but more taken daily for years just might raise your long-term risk of colorectal cancer or cognitive decline. If higher amounts are unavoidable (for example, until all prenatal vitamins switch from folic acid to folate), taking additional folate will very likely offset the folic acid still found in the multiple. If you’re apprehensive, consult a physician skilled and knowledgeable in nutritional and natural medicine.



It’s very likely that within a relatively short time enough responsible supplement suppliers will switch from folic acid to folate in all their supplements, individual and combination, so you won’t need to read all the labels so closely to make sure you’re getting folate and not folic acid.



One last point you may be wondering about: Is there such a thing as “too much of a good thing” when it comes to naturally occurring folate supplementation?



Unless you have vitamin B12 deficiency or cancer, it’s very unlikely to be a problem. In the case of vitamin B12 deficiency, supplemented folate—even naturally occurring folate—can “cover up” some of the deficiency signs in blood tests. But preventing that is simple: Take extra vitamin B12 whenever you take extra folate! Some suppliers even combine the two, or put them with the rest of the B-complex vitamins.



But if you have cancer, it’s of course best to discuss folate (not folic acid) supplementation with a physician skilled and knowledgeable in nutritional and natural medicine. To find one in your area, contact the American College for Advancement in Medicine. JVW



Where to get it: Naturally occurring folate in supplements



At present, two types of folates that occur naturally in foods are available as over-the-counter supplements. One is folinic acid, usually sold over-the-counter as “calcium folinate.” Calcium folinate is also available by prescription as Leucovorin®, which, unfortunately, is considerably more expensive and also contains FD&C yellow #10 and FD&C blue # 1, neither of which improves clinical results.



The other over-the-counter naturally occurring folate presently available is 5-methyltetrahydrofolate. It’s more expensive than over-the-counter calcium folinate, but more likely to be effective for individuals with “hidden” genetic defects in folate metabolism.



There’s also at least one B-complex and one multiple vitamin-mineral combination containing calcium folinate and methylcobalamin (the more metabolically active form of B12) available over-the-counter. By the time this newsletter is printed, it’s very likely more than one of each of these will be available, too.



The availability of supplemental folates that occur naturally in foods has solved another problem I’d been observing in a minority of individuals since the 1970s. Although the large majority of people who tested poorly for individually optimal levels of folate on a test called the neutrophilic hypersegmentation index (see “Overlooked blood test could be the key to your good health” below) significantly improved their levels by taking folic acid supplements, a small but significant number had little to no improvement at all. For this group, all I could tell them was to eat as much folate-containing food as possible, and forget the folic acid supplements.



But since supplemental calcium folinate and 5-methyltetrahydrofolate have become available, nearly every patient with a previously abnormal neutrophilic hypersegmentation index has improved with their use.



Overlooked blood test could be the key to your good health



If you’re serious about good health and longevity, or if you have any chance at all of becoming pregnant, there’s an inexpensive but critically important blood test that’s too often overlooked. Although it’s simple, quick, and easy to do, many clinical laboratories don’t do it because there’s “no demand.”



It’s called the “neutrophilic hypersegmentation index.” It is a mouthful to say, but for decades it has been—and still is—the best test of your personal folate status. Not how your folate level compares with other peoples’, but how optimal your own level is.



To do that, the neutrophilic hypersegmentation index (NHI) determines what percentage of your neutrophils—a type of white blood cell—were supplied with an optimal amount of folate while they were growing and maturing. Of course, optimal is 100 percent. But before we get into how to boost your own score, it’s important to know some of the scientific background that explains why this test is so important.



When neutrophils are “born” and “incubate” in bone marrow, their chromosomes—DNA—arrange themselves into five segments. A final step in neutrophil DNA maturation is re-arrangement of those five segments into three. Normal folate metabolism is a key to this final step. Very shortly after the five-to-three segment DNA re-arrangement, the fully mature neutrophil is released from the bone marrow into the bloodstream, where it lives out its months-long life doing its job—one very important part of which is defending our bodies against germs.



But if there isn’t enough folate, the neutrophil’s DNA stays in five (instead of three) segments. When the neutrophil is needed, it’s released into the bloodstream anyway, where it’s called a hypersegmented (too many segments) neutrophil. Fortunately, a hypersegmented neutrophil can still fight germs as well as a “regular,” three-segmented neutrophil.



Planning a family? Why you MUST have this test



After a blood sample is drawn, a technician with a microscope can easily see and count the number of DNA segments in each neutrophil. The “hypersegmentation index” is the percentage of five-segment neutrophils counted in a total of one hundred neutrophils.



Neutrophils, other circulating blood cells, and the cells that line our gastrointestinal tracts are the most rapidly dividing cells in our bodies. So if there’s a shortage of any of the three key nutrients for keeping cell division normal—folate, vitamin B12, and/or zinc—these rapidly dividing cells are likely to show the effects first. So the “neutrophilic segmentation index” actually tells us whether the most rapidly dividing cells in our bodies have enough folate. If these cells do, then it’s very likely that every cell in our bodies has enough folate.



One of the saddest test reports I’ve had to share with anyone was an NHI of 47 percent reported for a woman who was already pregnant. As you may have expected, her baby was born with a birth defect.



Every woman who has any chance at all of becoming pregnant should have this test done! If it’s abnormal, and she’s planning on a pregnancy soon, she should take a series of folinic acid injections (see above “Where to get it: Naturally-occurring folate in supplements”. ) right away, preferably with the methylcobalamin form of vitamin B12, so there’s enough folate (and B12) immediately available for any newly conceived infant.



Why the rush? Well, the most common birth defect—neural tube defect—occurs on days 27–29 after conception, before many women are even certain that they are pregnant.



For the rest of us (as well as newly-folinic-acid-injected potential moms) an abnormal NHI means you need to take a closer look at your diet and make some necessary adjustments—most notably adding in more sources of folate, particularly green vegetables, beans, peas, brewer’s yeast, and (organic only!) liver. A folinic acid or methylfolate supplement is important, too, at least until the test normalizes.



A basic nutrient for cancer and heart disease protection



But pregnancy—or the possibility of pregnancy—isn’t the only time folate levels are important. Folate (along with vitamin B12 and zinc) are all critical to normal cell division and DNA repair, which means they’re all essential tools for cancer prevention. Adequate folate lowers the risk of a variety of cancers, particularly in the gastrointestinal tract, but also breast, pancreatic, cervix, and lung.



It’s almost certain further research will add other cancers to this list. However, for those who already have cancer in any form, it’s not yet clear whether or not supplemental folate may accelerate cancer growth as fully oxidized folic acid has been found to do in some studies.



Along with vitamins B6 and B12, folate helps keep levels of the natural human metabolite homocysteine low in our bodies. Considerable research shows that increasingly higher homocysteine levels are associated with increasingly higher levels of cardiovascular disease and atherosclerosis.



It’s true that in 2008, researchers reported that supplemental folic acid (not folate), B12, and B6 were effective at lowering homocysteine but were ineffective in reducing “major cardiovascular events” and deaths, but (once again) it’s very likely that this study used folic acid—which isn’t as easily metabolized in older individuals (rather than methylfolate)— along with less-than-optimally active forms of vitamin B12 and B6.



So, despite this (likely flawed) study, if your homocysteine levels are high, I still recommend eating more folate-containing vegetables, and, if necessary, taking enough supplemental methylfolate, methylcobalamin, and pyridoxal phosphate to keep your level low. If you do, your risk of cardiovascular disease and atherosclerosis will likely be lower, too.



Research indicates that other benefits of supplemental folate may include reduction of stroke risk and macular degeneration, and improvement in depression, as well as improvement in memory and mental agility in older individuals.



When enough is enough



I’ve been using this test as part of routine “good health” testing for nearly everyone for over 30 years, and rarely see a result of under 5 percent (which shows insufficient folate). So the goal is always to bring that level as close to 0 percent as possible.



But if you want to be really “engineering precise,” a level of 1 to 2 percent hypersegmented neutrophils—meaning that 98 to 99 percent of those white cells received enough folate—may be the best outcome to aim for. Why isn’t 0 percent even better? An engineer friend once explained it like this: “Once I get to 0 percent, there’s no -10 or –20 percent reading to tell me that it’s 10 or 20 percent more than I really need, so I’m going to keep mine very slightly under rather than go over.”



It’s a good point—and leads to the next question: Is there any danger of “overdose” with folate? Except when cancer is already present, it’s not very likely. I’ve never seen it happen in over 35 years of practice. But no one knows for certain. So keeping your NHI at a level of 1 to 2 percent ensures that your folate levels are optimal without “overdoing” it.



And increasing folate-containing foods in the diet and (in the majority) adding supplemental folate almost always brings the test to that optimal level.



The NHI is simple enough to be done by any laboratory with a microscope and a skilled technician, but many labs still don’t do it. Why? Well, it requires a smear of blood on a microscope slide and isn’t done by machine. However, blood specimens can also be sent to Meridian Valley Laboratory in Washington state, where state law makes it possible for individuals to order their own lab tests.



JVW



Products

Jett & I take:

http://www.vitacost.com/Source-Naturals-MegaFolinic It divides well with a pill cutter & then I crush it to make sure he can ingest it.



and I also take:

http://www.vitacost.com/Metagenics-FolaPro-60-Tablets but, it's a tablet and gets destroyed if you want to divide it, so next time, I'm getting this one:

http://www.vitacost.com/Thorne-Research-5-MTHF-5-Methyl-tetrahydrofolate

because it's a capsule.

I included both of these because folinic acid is used for some ARN and ADN synthesis and methylfolate is mainly used for methionine regeneration so both are needed see: http://www.knowyourgenetics.com/The%20Methylation%20Pathway_files/supplmentation-1.jpg

Supposedly moms with MTHFR mutation or methionine sintasa mutation will benefit more from methylfolate. (I don't know if I have it, but I'm just assuming I do because of the symptoms and the fact that Jett has DS.)

Children with DS who don't have the same mutation as the mother will benefit more with folinic acid, but some of them also carry the same mutation as the mother and some of the father too.

Some with DS react adversely to folinic acid because they seem to have the mother and or father's mutation because folinic acid converts back to folic acid. (But you would know if it caused a problem by now.)

So you can test your child for those mutations too or check how s/he reacts to folinic acid and other methyl donors if s/he is ok with that, probably just folinic acid is best for him rather than methylfolate because if he does not have the mthfr mutations his methylfolate can accumulate.

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Abnormal Folate and Methyl Metabolism can Lead to DNA Hypomethylation and Abnormal Chromosomal Segregation Increasing the Risk for Having a Baby with Down Syndrome

Abnormal Folate Metabolism and Mutation in Methylenetetrahydrofolate
Reductase Gene May Be Maternal Risk Factors for Down Syndrome;
James, S. Jill, et al; American Journal For Clinical Nutrition,
volume 70, number 4, October 1999

Scientists recently reported their preliminary study findings and stated that mothers of children with Down syndrome often cannot efficiently metabolize the B vitamin, folic acid.

These researchers had found that almost 60% of the mothers of children with Down syndrome had a mutation which resulted in reduced efficiency of an important enzyme. This genetic abnormality hinders the metabolism of folic acid, and the defective process (known as maternal
non-disjunction) is responsible for 95% of all cases of Down syndrome, according to these scientists. About 80% of Down syndrome fetuses spontaneously abort, they reported

This is especially important for women of pregnancy age since they need that extra folic acid well before they get pregnant. It takes time for the human system to build up a reserve of the vitamin, and a lack of sufficient folic acid at the time the pregnancy begins may result in serious brain and spinal cord birth damage as the fetus develops. There have been hints that folic acid might play a role in other birth defects.

Down Syndrome and Folate Metabolism - 2

www.healthline.com/blogs/pregnancy_childbirth/2007/06/down-syndrome-and-folate-metabolism-2.html

Kenneth F. Trofatter, Jr., MD, PhD Director of Maternal-Fetal Medicine and Professor of Clinical Obstetrics
in the Department of Obstetrics and Gynecology of the University of South Carolina

Why is folate metabolism and the methylenetetrahydrofolate reductase (MTHFR)
gene are important?

MTHFR is an enzyme that requires folic acid to convert homocysteine to methionine (an important amino acid) and when this does not occur, homocysteine can accumulate. When this occurs in a developing embryo as the result of either folate deficiency or certain mutations in the
MTHFR gene, this may have a ‘toxic’ effect, increasing the risk for neural tube defects and certain cardiovascular abnormalities. This same biochemical pathway is also essential for the production of a substance called S-adeneosyl methionine that is an essential intermediate in
pathways that add methyl (CH3) groups to nucleic acids (DNA; RNA), proteins, neurotransmitters, and phospholipids, a process that plays an important regulatory role in the biological functions of each of these.



On the basis of evidence that abnormal folate and methyl metabolism can lead to DNA hypomethylation and abnormal chromosomal segregation,” James and colleagues (Am J Clin Nutr 1999;70:429-30) hypothesized in 1999 that young women with the most common MTHFR mutation (C677T) might be at greater risk for having a baby with Down syndrome than their peers who
do not have the mutation. In this study, they evaluated the frequency of the C677T mutation, plasma homocysteine levels, and lymphocyte methotrexate cytotoxicity as indicators of functional folate status in 57 mothers of Down syndrome children and 50 matched controls.
Findings of significantly higher levels of plasma homocysteine and increased sensitivity of lymphocytes to methotrexate cytotocity in the women with Down syndrome babies supported their hypothesis that abnormal folate and methyl metabolism might contribute to the risk
for trisomy 21. Indeed, the women with the C677T MTHFR mutation in this small study had a 2.6-fold higher risk for having a baby with Down syndrome than those who did not.

A subsequent study published by Hobbs and colleagues the next year (Am J Hum Genet 2000;67:623-30) confirmed the preliminary results above. In a cohort of 157 women with Down syndrome babies and 150 matched controls, these investigators not only looked at the prevalence of the C677T MTHFR mutation (technically ‘polymorphism’), but also the
prevalence of a common mutation (A66G) in the methionine synthase reductase (MTRR) gene, another enzyme essential for normal folate metabolism. The presence of the C677T MTHFR mutation was associated with a 1.9-fold greater risk, the presence of the homozygous A66G
MTRR mutation a 2.57-fold risk, and the presence of both polymorphisms a 4.08-fold risk for having a baby with Down syndrome.

Since the publication of the first two studies cited in my last post related to this issue, various groups around the world have investigated the association of abnormalities in folate metabolism and methylation pathways and the risk for Down syndrome. Most studies have demonstrated such an association, although specific findings have differed based on the genetic polymorphisms studied and geographic locations of the study populations. Although these ‘inconsistencies’ might at first lead to doubts about the original findings, they probably can be explained by other differences in genetic backgrounds (geographic variations in types and combinations of polymorphisms) and even geographic differences in dietary habits that might alter the overall deleterious effects of the polymorphisms.

For example, we know that the most common gene mutation in MTHFR (C677T)
(methylenetetrahydrofolate reductase) does not completely inactivate the gene, but reduces its efficiency in catalyzing the biochemical reactions of importance. We also know that this deficiency can be overcome by supplementation with folic acid (hence ‘genetic predisposition’ and ‘environmental factors’) and greatly reduces the rates of neural tube defects. Therefore, women in parts of the world where the ‘usual’ diet is rich in folic acid may not necessarily demonstrate an association between MTHFR C677T and Down syndrome, although other genetic polymorphisms in these metabolic pathways, not readily overcome by folic acid alone, might still show a relationship.



Two studies from Italy illustrate my argument in this regard. In 2003, Stuppia and colleagues (Eur J Hum Genet 2003;11:5) reported that they found no significant difference in MTHFR C677T in 64 mothers of Down syndrome babies compared to 112 matched controls. However, a recent study by Scala, et al., (Genet Med 2006;8:409-16) presented a case-control study of seven polymorphisms of six genes involved in homocysteine/folate pathways and analyzed risks, not only of the single polymorphisms, but of combinations of these as well as well. They demonstrated significant associations between risk for Down syndrome and the presence of either another MTHFR polymorphism (1298C) or of the reduced-folate-carrier1 (RFC1) 80G gene. Furthermore, although carriers of the MTHFR C6777T polymorphism alone were not found to be at greater risk (supporting the earlier study by Stuppia, et al.), women who carried both the MTHFR C677T and 1298C were at significantly greater risk than those carrying either polymorphism alone. (Another recent study by Acacio, et al.
(Prenat Diagn 2005;25:1196-9) from Brazil found women carrying the combination of these same two polymorphisms conferred a 5.7-fold risk for having a baby with Down syndrome).

Chadefaux-Vekemans and colleagues (Pediatr Res 2002;51:766-7) and Bosco, et al. (Am J Med Genet 2203;121:219-24) also found no increased risk associated with MTHFR C677T alone among French women and Sicilian women with Down syndrome babies, but let me remind you, the dietary habits of French, Italian, and Sicilian women, generally, include much higher intakes of folic acid rich foods than that of American women. And, interestingly enough, in the latter study, risk associations were found with both a polymorphism (MTR A2756G) in methionine synthase (3.5-fold risk), yet another enzyme involved in these metabolic pathways, and elevated homocysteine levels (6.7-fold risk). Women who carried both MTR A2756G and MTRR A66G were at 5-fold increased risk.

Other studies from around the world seem to support the association between abnormalities in folic acid/methylation metabolism and the risk for having a baby with Down syndrome, despite population variations. O’Leary and colleagues in Ireland (Am J Med Genet 2002; 107:151-5) evaluated both the MTHFR C677T and the MTRR A66G polymorphisms among women who had Down syndrome babies in their country. They too found no correlation MTHFR C677T alone, but found a significant increase in risk in women who carried either one or two copies of the MTRR A66G polymorphism. Furthermore, women who had both the MTHFR C677T (one or two copies) and two copies of the MTRR A66G polymorphisms were at almost 3-fold risk for having a baby with Down syndrome. The only women who had elevated homocysteine levels were those who carried the MTHFR C677T polymorphism, so the increased risk associated with the MTRR A66G polymorphism did not seem to be reflected in the homocysteine levels of their study population. Rai, et al., (J Hum Genet 2006; 51:278-83) in India found that women who were homozygous (carried two copies) for either the MTHFR C677T or A1298C polymorphisms had risks 7-fold and 4-fold, respectively, and in the case of the former, all the women who had a Down syndrome baby were less than 31 years of age. No such association between age and Down syndrome risk was found for carriers of MTHFR A1298C.



Down syndrome results from the presence of 3 copies of chromosome 21. In 90-95% of cases, the extra chromosome is maternal in origin and results from a failure of normal chromosomal segregation (nondisjunction) during meiosis. This produces one egg (ova) that has 24 chromosomes (22 different chromosomes + 2 copies of chromosome 21) and one egg that has only 22 chromosomes (with no copies of chromosome 21). If the first egg is fertilized by a normal sperm containing 23 different chromosomes, we end up with a baby that has 47 chromosomes rather than 46, and in this case Down syndrome. If the second egg is fertilized, the embryo that is produced has only 45 chromosomes and is nonviable if it has only one copy of chromosome 21 (from the father). Although the risk for trisomy 21 increases with maternal age, most children with Down syndrome are actually born to women less than 30 years of age.

The treatment suggested by this doctor is high doses of folic acid + B vitamins + baby aspirin or anticoagulants*.

MTHFR: 5,10-Methylenetetrahydrofolate Reductase (Þ 5-Methyl-Folate)

Simplified representation of the folate pathway showing the interaction of the various folate methylation states with purine and pyrimidine biosynthesis and the methylation cycle. Genes/proteins are indicated by ovals, whereas the rounded rectangles represent cellular substrates and products of a given gene product. ABCB1, P-glycoprotein; ABCC3, multidrug-resistant protein 3; ATIC, 5-aminoimidazole-4-
carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase; AHCYL1, S-adenosylhomocysteine
hydrolase-like 1; DHFR, dihydrofolate reductase; FPGS, folylpolyglutamyl synthase; GART,
phosphoribosylglycinamide formyltransferase; MAT2A, methionine adenosyltransferase II alpha; MTHFD1, trifunctional methylenetetrahydrofolate dehydrogenase, cyclohydrolase, synthase; MTHFR, methylenetetrahydrofolate reductase; MTR, 5-methyltetrahydrofolate-homocysteine methyltransferase; MTRR, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase; PPAT, phosphoribosyl pyrophosphate amidotransferase; SLC19A1, solute-carrier family 19 (folate transporter), member 1;

http://www.lipidworld.com/content/5/1/1/figure/F1

http://www.dramyyasko.com/Diagrams_files/supplmentation.jpg

Supplementation Cycle

5 formyl THF=folinic acid=leucovorin
5 Methyl THF= L-methylfolate=Deplin (medical food)

Folate is one of the 13 essential vitamins. Dihydrofolate, a mixture of polyglutamates (ie, a number of glutamatic acid entities) is the form of folate obtained from dietary intake of green vegetables, yeast, liver, kidney, and egg yolk. Folic acid is the synthetic form of folate contained in over-the-counter vitamin supplements (usually mixed with several other vitamins and nutrients and present in low doses). Folic acid is also the synthetic form of folate contained in prescriptions written by a licensed practitioner in higher doses for medical use.

Dihydrofolate and folic acid are converted to monoglutamate entites by the enzyme alpha-L-glutamyl transferase in the intestinal wall as they are absorbed.47 Once absorbed, monoglutamate entities are converted to MTHF, the form of folate that passes into the brain and is utilized by trimonoamine neurons to facilitate neurotransmitter synthesis (Figures 1 and 4B). Normally, ingesting folate from dihydrofolate in the diet or from folic acid in synthetic supplements will result in adequate delivery of MTHF levels to the brain, especially in those individuals with the more efficient genotype (C677C) producing up to 100% of the enzyme methylene tetrahydrofolate reductase http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=1267

Treatment goals
Lower homocysteine and increase methylation with:

L-methylfolate 1 mg
Methylcobalamin 2 mg
Betaine or trimethylglycine
vit B6 as P5P
Magnesium

Recommendations

…the active form of folate called L-5-methyl tetrahydrofolate as Metafolin. Unlike folic acid, this active form of folate requires no additional metabolic steps to be utilized by the body, making it a preferred choice for many individuals. Folate is an essential nutrient for many body processes, including hormone metabolism, DNA synthesis, homocysteine metabolism, and nervous system function.

Metafolin is the end product. Solgar makes a cheaper version.

http://www.google.com/products/catalog?q=Metafolin&oe=utf-8&rls=org.mozilla:en-US:official&client=firefox-a&um=1&ie=UTF-8&tbm=shop&cid=16258278265168263645&sa=X&ei=1-bcTd0JzLi2B-_joakP&ved=0CD8Q8wIwAg&biw=1024&bih=615#

http://www.iherb.com/Metagenics-FolaPro-120-Tablets/20940?at=0

Genetic polymorphisms involved in folate metabolism and elevated plasma
concentrations of homocysteine: maternal risk factors for Down syndrome in Brazil.

Biselli JM, Goloni-Bertollo EM, Zampieri BL, Haddad R, Eberlin MN, Pavarino-Bertelli EC.

Unidade de Pesquisa em Genética e Biologia Molecular, Faculdade de Medicina de São José do Rio Preto,
São José do Rio Preto, SP, Brasil.

The aim of the present study was to investigate the effect of polymorphisms C677T and A1298C in the methylenetetrahydrofolate reductase (MTHFR) gene, A2756G in methionine synthase reductase (MTR) gene and A80G in reduced folate carrier 1 (RFC1) gene, and plasma homocysteine (Hcy), on the maternal risk for Down syndrome (DS). Seventy-two DS mothers and 194 mothers who had no children with DS were evaluated. The investigation of the MTHFR C677T, MTR A2756G and RFC1 A80G polymorphisms was
performed by polymerase chain reaction and enzyme digestion and the MTHFR A1298C polymorphism by allele-specific polymerase chain reaction. Hcy quantification was carried out by liquid chromatography-tandem mass spectrometry. The median number of polymorphic alleles for the four loci tested was greater in DS mothers compared to the control group, and the presence of three or more polymorphic alleles increased the risk for having a child with DS 1.74 times. Elevated maternal risk for DS was also observed when plasma Hcy concentration was higher than 4.99 micromol/L. In conclusion, the presence of three or more polymorphic alleles for MTHFR C677T, MTHFR A1298C, MTR A2756G, and RFC1 A80G, and plasma Hcy concentrations higher than 4.99 micromol/L are maternal risk factors for DS.

Analysis of seven maternal polymorphisms of genes involved in
homocysteine/folate metabolism and risk of Down syndrome offspring.

Scala I, Granese B, Sellitto M, Salomè S, Sammartino A, Pepe A,
Mastroiacovo
P, Sebastio G, Andria G.
Department of Pediatrics, Federico II University of Naples, via S. Pansini
5,
80131 Naples, Italy.

PURPOSE:
We present a case-control study of seven polymorphisms of six genes involved in homocysteine/folate pathway as risk factors for Down syndrome. Gene-gene/allele-allele interactions, haplotype analysis and the association with age at conception were also evaluated.

METHODS: We investigated 94 Down syndrome-mothers and 264 control-women from Campania, Italy.

RESULTS: Increased risk of Down syndrome was associated with the methylenetetrahydrofolate reductase (MTHFR) 1298C allele (OR 1.46; 95% CI 1.02-2.10), the MTHFR 1298CC genotype (OR 2.29; 95% CI 1.06-4.96), the reduced-folate-carrier1 (RFC1) 80G allele (1.48;95% CI 1.05-2.10) and the RFC1 80 GG genotype (OR 2.05; 95% CI 1.03-4.07). Significant associations were found between maternal age at conception > or = 34 years and either the MTHFR 1298C or the RFC 180G alleles. Positive interactions were found for the following genotype-pairs: MTHFR 677TT and 1298CC/CA, 1298CC/CA and RFC1 80 GG/GA, RFC1 80 GG and methylenetetrahydrofolate-dehydrogenase 1958 AA. The 677-1298 T-C haplotype at the MTHFR locus was also a risk factor for Down syndrome (P = 0.0022). The methionine-synthase-reductase A66G, the methionine-synthase A2756G and the cystathionine-beta-synthase 844ins68 polymorphisms were not associated with increased risk of Down syndrome.

CONCLUSION: These results point to a role of maternal polymorphisms of homocysteine/folate pathway as risk factors for Down syndrome.

http://www.ncbi.nlm.nih.gov/pubmed/16845273?



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*Should Omega-3 be Part of Your Anticoagulant Therapy?

Omega-3 as an anticoagulant. Does it work?
With heart disease on the rise, many people are turning to omega-3 as part of their anticoagulant therapy. Is this effective? Is it safe? These are some of the questions heart patients are asking and will be discussed in this article.

Omega-3 and anticoagulant therapy
Not yet familiar with omega-3, here's what you need to know. It is an essential fatty acid that plays in important role in brain and cardiovascular health. Omega-3 is a natural blood thinner that helps blood flow easier through the arteries and lowers the risk heart attacks, strokes, and heart disease.

Many types of anticoagulant drugs are available to thin blood, but most of these are very strong and contain serious side effects such as hemorrhagic stroke. Some people take aspirin as a blood thinner. But over time aspirin has the tendency to eat away at intestinal lining causing bleeding and ulcers. For these reasons, many patients turn to omega-3 as a natural blood thinner.
Omega-3 as an anticoagulant - does it work?
As a result of studies performed at the University of Maryland, professionals have come to the following conclusion:
"Strong evidence from population-based clinical studies suggests that omega-3 fatty acid intake (primarily from fish) helps protect against stroke caused by plaque buildup and blood clots in the arteries that lead to the brain. In fact, eating at least 2 servings of fish per week can reduce the risk of stroke by as much as 50%."
This encouraging news is a mere sample of many more studies backing up these findings. However, Robert O. Bonow, MD, of Northwestern University in Chicago is trying to "temper" enthusiasm until further studies are completed.
There is strong evidence that omega-3 consumed in the form of fish oil is very effective in treating heart disease. Heart disease is serious. You should always consult your doctor before attempting to treat yourself with omega-3. If you are interested in trying this method of anticoagulation therapy, consult your doctor before taking omega-3.

From: http://www.heartdiseasetreatments.net/benefits-of-omega-3-as-an-anticoagulant-discover-natures-secret-ingredient-for-a-healthy-heart.html

Omega-3 full of fat acids are organic blood thinners.

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Tests and Treatment for Moms

EGCG Green Tea Extract For Memory

Overview of Benefits

Green Tea, and especially the component epigallocatechin gallate (EGCG), provide potent neuroprotective effects to the brain as well as improved learning abilities.

Improved memory learning ability. In laboratory animals, administration of green tea catechins (including EGCG) showed improved spatial memory and learning ability of the animals in maze navigation studies. The animals receiving the green tea had much less oxidative stress activity in the hippocampus (memory) area of the brain. According to the researchers, the improved memory is most likely due to significant antioxidant protection provided by the green tea.

Neuroprotective for neurogenerative diseases. EGCG has a protective effect on neurons. One study showed the ability of EGCG to protect dopaminergic neurons against a herbicide known to be toxic to these cells. Further studies have shown that EGCG is protective to neurons injured due to neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases.

Neuro Rescue role as an iron-chelator and antioxdant. Neurodegeneration in Parkinson’s and Alzheimer’s disease are characterized by the accumulation of iron at the location where neuron cell death occurs. Iron increases levels of oxidative stress at the site, and is believed to be a major factor in the neurodegenerative process. EGCG is an iron chelator, and can remove the iron, thereby eliminating a significant source of oxidative stress. In addition, EGCG is an potent antioxidant, which further mitigates the oxidative stress of the neuron.

Greatly improves levels of antioxidant enzymes and antioxidants in the brain. The brain is very susceptible to oxdiative stress related damage because of its high content of polyunsaturated acids. EGCG has been shown, in lab animals, to improve the activity of antioxidant enzymes such as superoxide dismutase, as well as support increased levels of the antioxidants tocopherol, ascorbic acid and glutathione. EGCG is therefore a good neuroprotective agent (from oxidative stress) for the aging brain.

Source: http://www.memoryaction.com/content/Ingredient_Research.htm

-------

There's a lot of information about EGCG on the Changing Minds blog. www.changingmindsaboutdownsyndrome.blogspot.com Start at the beginning DYRK1A and DSCR posts.

______

There is a possible clinical trial underway concerning EGCG and Down syndrome.
http://www.recherchefondationlejeune.org/en/dyrk1a.php

_____

Green Tea May Cut Alzheimer’s Risk...

Green tea, the popular beverage drunk by millions in Asia and, increasingly, by many in the U.S. as well, may have benefits against Alzheimer’s disease, researchers report. The beverage contains a compound called EGCG that appears to reduce the formation of beta-amyloid, a toxic protein that builds up in the brains of those with Alzheimer’s disease. Although the studies were carried out in mice and may not apply to humans, scientists are motivated to continue research into the possible benefits of green tea for people suffering from memory loss and dementia.

The researchers, from the University of South Florida, gave high doses of the green tea compound EGCG (for epigallocatechin-gallate) to mice that had been genetically altered to produce beta-amyloid. After several months of daily EGCG injections, brain cells in treated mice contained 54 percent less beta-amyloid. The buildup of beta-amyloid is a hallmark of Alzheimer’s disease, resulting in the death of healthy cells vital for memory and the formation of abnormal structures called plaquesin the brain. Many researchers believe that by blocking formation of beta-amyloid, memory loss and other troubling symptoms may be slowed or halted.

“The findings suggest that a concentrated component of green tea can decrease brain beta-amyloid plaque formation,” says researcher Jun Tan, M.D., Ph.D., director of the Neuroimmunology Laboratory at the University of South Florida. “If beta-amyloid pathology in this Alzheimer’s mouse model is representative of Alzheimer’s disease pathology in humans, EGCG dietary supplementation may be effective in preventing and treating the disease.”

Sipping Tea Not Enough

Green tea contains many different compounds called flavonoids that have powerful antioxidant activities. Antioxidants act to mop up free radicals, natural oxygen compounds that, in excess, can damage cells. EGCG is the main antioxidant in green tea. It is thought to have benefits for heart and blood vessel health, and scientists are studying it for its possible benefits in protecting against cancer as well.

But drinking green tea or taking green tea supplements rich in antioxidants may not be enough to cut Alzheimer’s risk. The researchers showed that other flavonoids in green tea actually block EGCG’s ability to prevent the harmful buildup of beta-amyloid. “This finding suggests that a green tea extract selectively concentrating EGCG would be needed to override the counteractive effect of other flavonoids found in green tea,” says Doug Shytle, Ph.D., of the University of South Florida. In addition, the scientists note that further research is needed to determine whether EGCG actually reduces memory loss and reduces plaque formation in mice. The next step would be to test EGCG extracts in people.

In the meantime, taking a tea break won’t hurt and may help. Earlier research suggests that green tea as well as other types of tea may have benefits for brain health. At the least, a cup of tea can provide a pleasant stress-reducing break during the day.

By www.ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Source

Rezai-Zadeh K, et al: “Green Tea Epigallocatechin-3-Gallate (EGCG) Modulates Amyloid Precursor Protein.” Journal of Neuroscience, Volume 25. September 21, 2005, pages 8807-8814.


Source: http://www.memoryaction.com/content/Ingredient_Research.htm

References

1. Chen LW, et al. Chinese herbs and herbal extracts for neuroprotection of dopaminergic neurons and potential therapeutic treatment of Parkinson's disease. CNS Neurol Disord Drug Targets. 2007 Aug;6(4):273-81.
2. Tohda C, et al. Search for natural products related to regeneration of the neuronal network. Neurosignals. 2005;14(1-2):34-45.
3. Haque AM, et al. Long-term administration of green tea catechins improves spatial cognition learning ability in rats. J Nutr. 2006 Apr;136(4):1043-7.
4. Hou RR, et al. Neuroprotective effects of (-)-epigallocatechin-3-gallate (EGCG) on paraquat-induced apoptosis in PC12 cells. Cell Biol Int. 2007 Sep 1
5. Avramovich-Tirosh Y, et al. Neurorescue activity, APP regulation and amyloid-beta peptide reduction by novel multi-functional brain permeable iron- chelating- antioxidants, M-30 and green tea polyphenol, EGCG. Curr Alzheimer Res. 2007 Sep;4(4):403-11
6. Weinreb O, et al. The application of proteomics for studying neurorescue activity of the polyphenol (-)-epigallocatechin-3-gallate. Arch Biochem Biophys. 2008 Jan 13
7. Srividhya R, et al. Attenuation of senescense-induced oxidative exacerbations in aged rat brain by (-)-epigallocatechin-3-gallate. Int J Dev Neurosci. 2008 Apr;26(2):217-23

Products

Decaffeinated and fluoride-free liquid: bodyecology.com $20, or 3 for $16.96 each or 4 for $15.96 each. This is the product I will be buying next.
It contains 80 mg of polyphenols per 20 drops, 100 mg of polyphenols per 30 drops.

I use decaffeinated because I have a severe reaction to caffeine myself. I use: http://www.vitacost.com/Natures-Herbs-Caffeine-Free-Green-Tea-Power It has 383 mg per capsule. $6 Harder to dose, but I have more time than money.

Other moms recommend: http://www.vitacost.com/NSI-Teavigo-trade-Green-Tea-Extract-Caffeine-Free 150 mg per capsule. $16 on sale at vitacost until 4/19/11

http://www.vitacost.com/NSI-GreenSelect-Green-Tea-Extract-Phytosome NSI GreenSelect Green Tea Extract features GreenSelect Phytosome®, a standardized, caffeine-free green tea extract complexed with soy phospholipids for enhanced bioavailability and efficacy. Like the enhanced bioavailability, but don't like the soy, though...

Dosage

EGCG should be given every 4-6 hours.
As for dosage, an adult should take no more than 500 mcg in a 24 hour period. So I'd say once our kids weigh 100 lbs, 500 mcgs is safe.
To break that down, 50 mcgs per 10lbs a day. Jett weighs 16 lbs, so about 80 a day for him. (I will split the 383mcg capsule into 1/4s and give him a little bit every 6 hours until it's gone. I'm just easing him into it now.) Other moms make it easier and just take the 150 mg capsule and give 1/3 at a time.

Here is a website that a dad started about giving EGCG to his DS son it has dosage info:
http://dstoner.net/Math_Science/Downs.html

Side Effects

EGCG is an iron chelator, which is great for most of our kids. But if your child's iron is low, make sure you are giving him plenty of sources of iron. Jett's iron (at last blood test) was on the low side of normal. So I have added unsulphered, organic, blackstrap molasses to his diet and will soon introduce organic liver from grass fed cows.

EGCG decreases the absorption of folate and our children need it, so you have to supplement with folate. (See results of folinic acid deficiencies below.)
To address this, I doubled Jett's folinic intake to 400 mcgs (200 mcg twice a day) and always give it with B12. I also give EGCG an hour after I give Jett the other supplements to give the folate some time to absorb.

From Don Stoner (the father who has the web page on EGCG, where I first heard about its use with children with DS):
Hi All, I won't be able to give you any unbiased confirmation (since I'm Josh's dad, and I wrote
that web page) but I'll be happy to answer any specific questions. The original research that got me started with EGCG can be found
by following this link. (I hope I typed that correctly.) It's pretty technical, but I think I can answer most questions about that article. My experience with Josh is that as long as he is taking EGCG, he seems to remember stuff pretty much like a normal kid; but when he stops taking it, he doesn't remember stuff (just like a normal DS kid). The change only takes a day or two (either direction), and it's pretty obvious.

I wasn't able to find a study that did a G.B. / EGCG comparison. This source here claims that EGCG is roughly comparable to Aspirin (in that they have roughly the same anticoagulant properties). The same source comments that they are not aware of any studies comparing G.B. with Aspirin. (G.B., EGCG, and Aspirin can all inhibit blood coagulation, even alone but especially in combinations.) Oddly, this source here says that the small amount of vitamin K in EGCG can make anticoagulant drugs, such as warfarin, less effective. Vitamin K (spinach is a good source) is generally good as a relatively quick fix for bleeding problems ... but it can be a disaster for problems involving excessive clotting.

From Christy:

I'm passing along a link to an article posted on another listserv about "too much of a good thing can be harmful" referring to nine case reports of liver toxicity caused by ingesting too much EGCG.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1964900/

Here are some excerpts from the article:

• laboratory research with both rodents and dogs has shown that high doses of the most heavily studied green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), cause liver, kidney, and
  gastrointestinal toxicities.
• “To date, there have been nine anecdotal case reports of liver toxicity in humans associated with consumption of high doses [700–2,000 mg/day] of green tea from dietary supplements,” says lead author Joshua Lambert,
  an assistant research professor in the Department of Chemical Biology
  at Rutgers University.
• “In some cases, the subject stopped taking the supplement and the symptoms resolved, and then the subject started taking the supplement again and liver toxicity returned.” Such observations, albeit anecdotal,
  suggest that green tea supplements are not without risk.
• “People who take less than 500 mg [of green tea concentrate or preparation] per day and spread the dose out over the course of the day are unlikely to have toxic side effects,” says Yang.
• Yang adds that some Japanese publications report beneficial effects for the consumption of 10 cups of green tea a day with no apparent harmful effects.
• Yang and Lambert hypothesize that people with oxidative stress–related liver diseases such as hepatitis or cirrhosis may be at greater risk of toxic side effects from ingesting high doses of green tea polyphenols.
  “When a person’s liver is already under stress, toxic effects tend to
  become amplified,” Yang says.
• Conversely, he notes there are data showing that low or moderate amounts of green tea have a protective effect against both toxicity and carcinogenesis in target organs—once again supporting the adage
  “everything in moderation, nothing to excess.”

One thing I would take from this article if I were giving EGCG to my child is to spread the dose out throughout the day (like your body would get it if you were drinking green tea throughout the day). You wouldn't sit down and drink 10 cups of green tea at once - thus your body wouldn't get 10 cups worth of EGCG at once. Also, the statement about "those taking less than 500 mg EGCG at once are less likely to have toxic side effects" - I assume they are referring to adults, so keep that in mind when trying to convert the dose to a safe level for children.

Watch out for these:

Folic Acid Deficiency Symptoms

Folic acid deficiency causes very general symptoms such as:

• Fatigue and weakness
• Headaches and difficulty concentrating
• Palpitations
• Diarrhea
  
• In the early stages, the tongue may be red and painful leading to a smooth shiny surface in the chronic stages of deficiency.

The Three Stages of Folic Acid Deficiency

At the first stage of deficiency the plasma folate levels fall. If the diet does not contain adequate folate, the red blood cell (RBC) folate levels drop after three to four months. With continuing deficiency, the bone marrow cells and other cells become affected. This is stage three, the clinical stage of folic acid anemia. It occurs after approximately four to five months of deficiency. Folic acid anemia is called megaloblastic anemia.

Folic acid functions in DNA synthesis and therefore cell division. Without this important vitamin, cells such as red blood cells produced in the bone marrow, fail to divide properly. RNA continues to form and build up producing excess haemoglobin. The RBC becomes an immature enlarged non-functioning cell often containing excess haemoglobin. This is megaloblastic anemia.

Certain factors confuse the diagnosis of folic acid deficiency anemia. The folic acid anemia is identical to the anemia of vitamin B12 deficiency. Therefore, it is very important to rule out vitamin B12 deficiency before taking folic acid supplements for anemia; otherwise, the megaloblastic anemia of vitamin B12 may go on unnoticed. In addition, the factors that lead to folate deficiency, such as poor diet, malabsorption and alcoholism, affect other nutrients as well, so singling out folic acid as the cause is often difficult.

Testing for Folic Acid Deficiency

Serum folate levels reflect recent changes in folate intake whereas RBC folate measures the folate stored in the body. RBC folate is a more reliable test. These tests are available through a standard blood test from the doctor.

High homocysteine levels may also reflect low folate status but it may also be indicative of vitamin B12 and vitamin B6 deficiency.

Resources

Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ. Modern Nutrition in Health and Disease. 10 ed. Maryland: Lippincott Williams & Wilkins; 2006.

Gropper S, Smith JL, Groff JL. Advanced nutrition and human metabolism. Belmont, CA: Thomson Wadsworth; 2005.

Johnson LE. Folate [monograph on online] 2007 April [cited 2008 November]

Gentili A. Folic Acid Deficiency. [monograph online] 2007 19 September [cited 2008 November]

Read more at Suite101: Folic Acid Deficiency: The Causes, Symptoms, and Stages of Folate Deficiency and Anemia http://www.suite101.com/content/folic-acid-folate-deficiency-a79897#ixzz1GuI87ODM

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