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The Way Up Newsletter
Vol. 33, 04-15-02



VITAMIN B12 / FOLIC ACID / HOMOCYSTEINE


NAMASTE & WELCOME TO THE WAY UP NEWSLETTER!

Every day I come across someone who is taking supplements, & expecting improved health. Yet they are choosing a supplement program in a hit & miss fashion based upon articles read about this or that item. They read about beta-carotene, & buy a bottle. They read about Selenium, & buy a bottle, then Calcium, & so forth.
 
Because of the confusion & misinformation, one of this months topics is:
WHAT IS AN OPTIMUM SUPPLEMENT PROGRAM?

The other topics are:
THE IMPORTANCE OF VITAMIN B12, and THE IMPORTANCE OF FOLIC ACID.

I recommend one not take any individual nutritional supplement, unless first taking a good multivitamin mineral (which by itself covers many basic nutritional needs). It is impossible to build the walls & roof of a house without first laying a proper foundation.

Most nutrients are dependent upon the presence of other nutrients, as they work together to do their job, just as would happen with a PERFECT diet!!?? Singular supplementing, without a baseline balanced product can actually create deficiencies. For instance, if you are taking one of the single B vitamins without getting the whole complex of B’s you can actually cause a deficiency of those not supplemented. Or if you are taking only Calcium, & no Magnesium, you can add to a Calcium imbalance , & so on. So before you add any individual vitamin, mineral, or amino acid, have your Multi vitamin mineral in place. This rule does not apply for digestive enzymes , hormones, herbs, certain specialty products, & homeopathics which have unique functions not dependent upon a certain balance of nutrients.

WHAT IS A GOOD BASIC SUPPLEMENT PROGRAM FOR A REASONABLY HEALTHY PERSON?
CHILDREN: A good children's multivitamin mineral in the dosage resommended on the label
. An Essential Fatty Acid supplement
. Extra Vitamin C, 250 mg twice daily
. .
ADULT MINIMAL: High quality Multivitamin Mineral, as directed on bottle Vitamin C 1000 mg twice daily with meals
. Vitamin B Complex 1 with breakfast (for extra B + what is in multi)
. A sublingual B12/Folic Acid 1-2 under tongue in a.m.
. Fish Oil, or Flax oil caps, 2-3 twice daily with meals, or Essential Fatty Acid Complex 1 dropper full twice daily
. .
WOMEN OVER 35 &
THOSE OFF DAIRY :
Add extra Calcium/ Magnesium to total - including Multi
. Calcium 1200-1500 mg & Magnesium 1000-1500 mg daily in divided doses (magnesium dose can be limited by laxative effect in some)
. .
VEGETARIANS &
PREGNANCY / NURSING:
Add extra iron
. Use 2-3 of a sublingual B12/folic acid.
WHY ARE B12 & FOLIC ACID SO IMPORTANT?
These nutrients are especially critical for 2 reasons:

1 - There are so many conditions & commonly used drugs which deplete them or interfere with their absorption
2 - The deficiency of either can go undetected to cause great damage & suffering.

These 2 nutrients are addressed together because when supplementing one, the other must also be supplemented, again for 2 reasons:

1 - If there is a B12 deficiency & only folic acid is taken, it can mask some of the blood changes & clues that a B12 deficiency exists. Such masking can allow progressive & irreversible damage to take place in the brain, spinal column, & peripheral nerves. Further, folic acid must be present for the proper use of B12.
2 - Many of the same factors contribute to deficiencies of these 2 nutrients.
WHAT SPECIAL CONDITIONS REQUIRE ASSURED AMOUNTS OF B12 & FOLIC ACID?
The only non meat foods containing B12 are eggs, blue-green algae, & nori seaweed, so vegetarians are at risk for deficiency.
 
Those with low thyroid function have impaired B12 absorption, while those with high thyroid function have excessive loss of B12.
 
Most with stomach /GI disturbances are at risk, whether it be from intestinal malabsorption, inflammatory diseases, chronic diarrhea, parasites, tapeworms, low stomach acid, gastrectomy, or the depletion of a protein called “intrinsic factor”, secreted in the stomach by what are called parietal cells. Intrinsic factor only exists to extract B12 from food. Auto immune illnesses can act in the stomach, to prevent production of or to bind the intrinsic factor preventing B12 absorption. Such people may have anti-parietal cell antibodies which can be easily found on a blood test. As if absorption weren’t a big enough problem, there may be defects in molecules which transport B12 from the blood to the tissue, so though serum levels look normal, the cells are deficient. There are 12 different inherited disorders which affect absorption, transport, or intracellular metabolism of B12.
 
High mercury , lead or other heavy metals which can reduce B12 uptake in the cells. A significant percentage of my patients have metal toxicity. For more see the Metal Toxicity Newsletter.
 
The elderly are at risk, because B12 absorption is known to decrease with age. Also they are more likely to be low in folic acid, iron, calcium, & vitamin B6 which contributes to depleted B12. They are more likely to have low stomach acid, or to be on acid blockers which impair absorption. They use more laxatives which deplete the storage of B12. Research suggests that elderly people with “normal” serum B12 levels are still metabolically deficient in B12 & often respond positively to the addition of B12.
 
Pregnant & nursing women, as well as infants need extra amounts of B12 / folic acid
 
Alcoholics notoriously are deficient, as well as those with anorexia, malnutrition, general illness states, or chronic stress.
 
Those with AIDS, or asymptomatic HIV are often compromised re B12 status. This occurs at an early stage of the infection. Such low levels are associated with acceleration of the disease , while adequate B12 treatment is correlated with increased CDT4 cell counts & improved AIDS index. Studies suggest B12 deficiency may both increase susceptibility to catching the virus in the first place & promote the progression to AIDS. When HIV positive & B12 deficient the progression to AIDS will come 4 years sooner. The “poppers”, an alkyl nitrite inhalant “recreational” drug can inactivate B12. The use of “poppers” has long been associated with susceptibility to HIV infection. It is believed there is a B12 deficiency in about 50% of all AIDS cases.
 
Those with mental, or emotional illness, or retardation may also be vulnerable to low levels. Besides helping to maintain the structural integrity of the brain & nerves, B12 & folic acid are needed for the synthesis of the essential neurotransmitters serotonin, norepinephrine, & dopamine. These are critical regulators for mood, sleep, appetite, drive, motivation, movement, cognition & numerous brain functions. Studies have shown certain people with “treatment resistant” depression responded well to folic acid treatment, which also potentiated the effect of Prozac & helped to protect against side effects.

 
 
WHAT DRUGS/SUBSTANCES CAN CAUSE LOW B12 AND FOLIC ACID?
Besides antacids & laxatives, other drugs they which deplete B12 are Aspirin, & the other salicylates, Tricosal, Trilisate, Arthropan; diuretics such as Bumetanide, Ethacrynic Acid, Furosemide, & Torsemide; & steroid medications. ( Be sure to check generic names on your drugs)
 
High dose vitamin C supplementation without the addition of B12/folic acid can contribute to deficiency.
 
Birth control pills decrease both B12 & folic acid. This is of particular significance if a woman then decides she wants to get pregnant & stops birth control pills without starting supplements. It is well know that the birth defects of spina bifida, cleft palate & lip are caused by low folic acid levels in the mother, especially in the first 6 weeks of pregnancy. A B12 deficient infant will suffer severe developmental abnormalities.
 
Many of the same conditions which deplete B12 also decrease folic acid. The drugs which contribute to folic acid deficiency are many of those used to treat seizure disorders, such as: barbiturates, Tegretol, Depakote, Zarontin, Celontin, Primidone, Dilantin, & Fosphenytoin; many of which are also used in the psychiatric population. The whole class of non-steroidal anti-inflammatory meds such as Ibuprofen, Anaprox, Motrin, Naprosyn, Naprelan, Pamprin, Voltaren, etc deplete folic acid.
 
Other culprits are drugs used for stomach problems & esophageal reflux, such as Pepcid, Axid, Tritec, Cimetidine & Zantec; the immune suppressants Methotrexate , Azulfidine, & steroids; Indomethacin; Viox; Aspirin & the other salicylates; Colestid;
 
WHAT ARE THE ACTIONS & DEFICIENCY SYMPTOMS OF B12 & FOLIC ACID?
  • Depression
  • Mental lethargy
  • Withdrawal
  • Irritability
  • Poor memory
  • Confusion
  • Dementia
  • Psychosis-paranoia
  • Insomnia
  • Digestive disturbances
  • Diarrhea
  • Weakness
  • Numbness
  • Stiffness/spasticity
  • Headaches
  • Restless legs
  • Burning feet
  • Increased sensitivity to pain
  • Sore tongue
  • Lesions at corners of mouth
  • Anemia (megaloblastic)
  • Shortness of breath
  • Low white blood cell count
  • Lowered resistance to infection, decreased antibody formation
  • Graying hair
  • Toxemia of pregnancy
  • Premature births
  • Increased risk of certain birth defects
  • Sprue
  • Weight loss
  • Anorexia (appetite loss)
 
WHAT IS THE HOMOCYSTEINE CONNECTION?
Those who read health articles in the general press have likely come across information about homocysteine. Homocysteine is a normal necessary substance in the body produced from the metabolism of an essential amino acid called methionine. (All amino acids are components of protein). The homocysteine, in turn, converts to a detoxifying amino acid called cysteine, a substance called ATP which is critical in producing energy in the cells, SAMe & also back to methionine. This occurs when all is working as it should be. But these conversions do not take place properly if adequate amounts of B12, Folic acid, & Pyridoxal 5 phosphate (B6) , are not present. When the homocysteine does not metabolize properly , it then accumulates to unhealthy high levels & becomes a silent formidable enemy.
 
Elevated levels of homocysteine are associated with a greater risk for cardiovascular diseases such as heart attacks, peripheral arterial disease, strokes, venous thrombosis, & carotid artery stenosis. In fact, the homocysteine level is the strongest predictor of both overall mortality from any cause & mortality from cardiovascular causes. Cardiovascular disease accounts for 43% of all deaths in the U.S.
 
Excess homocysteine is directly toxic & damaging to the walls of the blood vessels which helps lead to atherosclerosis. It also stimulates an inflammatory substance in the platelets called thromboxane which helps cause clots. It may also contribute to the oxidation of LDL. (Imagine how much good could be done if all cardiologists included a multivitamin mineral, B12, folic acid, extra B6, co-enzyme Q10, & policosonal in their treatment plans!)
 
Excess homocysteine also contributes to the development of Alzheimer’s, arthritis, & diabetes. A new study in the New England Journal of Medicine involving 1092 subjects over the course of 8 years found that for every 5 micromoles /l increase of homocsyteine the risk of dementia or Alzheimer’s was increased by 40%. Homocysteine levels over 14 nearly doubled the risk of Alzheimer’s. Clearly homocysteine is not the only contributing factor to these illnesses, but plays its deadly part.
 
Interesting other studies have shown high levels to be associated with miscarriage, which was corrected when the women were supplemented with folic acid 15mg daily & B6 750 mg daily, which are quite large doses. Another study showed levels greater than 6.3 were associated with an increased risk for cervical cancer.
 
WHAT TESTS CAN BE DONE TO SEE IF THERE ARE DEFICIENCIES?
One can get a homocysteine blood test by itself, or a panel such as the Comprehensive Cardiovascular Assessment, which contains this test as well as numerous other evaluations for cardiovascular risk. The optimal safe range for homocysteine is less than 6, the lower the better.
 
The most exciting & informative new test which has just become available,is the Cardio Genomic Profile http://www.genovations.com. This test identifies gene variations which foretell the increased likelihood of developing cardiovascular disease. It can identify if you are at risk for the development of high homocysteine so you can really act preventatively. The test identifies your genetic risk for increased blood clotting, increased blood pressure, cholesterol imbalance, & inflammatory cardiovascular disease. It is also useful if you already know you have these problems, because it tells you how to change your genetic predisposition! You can then retest in several months to make sure mission accomplished. The test can be done at home by collecting mouth wash samples & sending in the kit. The DNA in buccal cells is analyzed. You would have to ask your Dr to order the kit. Because it is so new, insurance does not yet cover it, so if that is an issue, you might use some of the other tests mentioned here-but this is my current preference.
 
Many Drs only order a serum B12 & serum folic acid test. If these are normal, they consider all to be fine in this arena. This is simply not true. These tests are only useful when they are low, which then indicates a substantial deficiency. Numerous studies have shown a positive response to treatment with B12/folic acid, when the blood levels were normal. The amount in the blood tells nothing about transport to, uptake, or utilization by the cells.
 
A useful indirect measurement of B12 deficiency is the urine or blood methyl malonic acid test. When this substance is elevated, there is a B12 deficiency.
 
A complete blood count (CBC) can be useful in those people who manifest blood changes, but not all do. In fact, one can be sufficiently low to exhibit neurological damage without showing any blood cell changes. Again, when there is overt anemia of what is called the megaloblastic or macrocytic type, there is likely a B12/folic acid problem. But it is useful to look for more subtle signs such as low normal total number of red blood cells, large red blood cells(high normal MCV) , low normal total number of white blood cells, low normal platelets, or low normal neutrophils ( a type of white blood cell).
 
There is a good blood test called the Functional Intracellular Analysis.
 
WHAT FORMS OF B12/FOLIC ACID ARE BEST TO TAKE?
Vitamin B12 comes in several chemical forms & folic acid in two forms. The most common & least expensive B12 is cyanocobalamin. This is fine to use for basic supplementation. And plain folic acid is fine for a basic program. There are also the methyl-, hydroxy-, & adenosyl- cobalamin forms of B12 which are more expensive & previously have been less available.
 
Dietary or supplemental cyanocobalamin converts in the body to the other forms listed here, especially Methylcobalamin (MeCb). Folic acid must be present for this conversion to take place. The folic acid must be in the coenzyme form called L- 5 methyl tetrahydrofolate. A properly functioning body would have converted regular dietary or supplemental folic acid to this coenzyme form. When there are diseases, sometimes the folic acid does not convert properly, & one would have to supplement with the L-5 methyl tetrahydrofolate instead.
 
The methyl cobalamin (MeCb) is the most active form of B12 in the body, especially in the brain & nervous system. There is the belief the MeCb has some therapeutic applications not as well achieved by other forms of B12. MeCb is also utilized more efficiently & has better tissue retention. For this reason much of the recent research has been done using this MeCb. Some of the research uses the injectable, some the sublingual form. When possible, I suggest a combination of the 2 when one is treating a significant health problem.
 
At the risk of going on interminably, can’t help but think some would like examples of when to use these supplements in higher doses, so
WHAT ARE EXAMPLES OF WHEN YOU WOULD USE HIGHER THERAPEUTIC DOSES?
. Those with: Pernicious anemia, an inherited defect in the absorption of B12, or with any anemia associated with large red blood cells.
  High levels of MeCb are needed to regenerate nerve cells & the covering of the long nerves, called myelin sheath. MeCb also protects against neurotoxicity. Thus those with a variety of neurological disorders may respond well.
  In studies on Bells Palsy (a painful condition the facial nerve), patients treated with 1.5-6 mg MeCb daily recovered in an average time of 1.95 weeks. Those treated with the usually prescribed steroids took an average of 9.6 weeks to recover.
  Parkinson’s patients. Oral MeCb helped to delay the progression of Parkinson’s & to maintain a longer benefit from Sinemet (a drug for Parkinson’s)
  Those with ALS (Lou Gehrigs Disease), Multiple Sclerosis(doses up to 60 mg/d for this) Muscular Dystrophy, Peripheral Neuropathy, restless legs, neurological aging, dementia, depression, psychosis, mood swings.
  Infertile men treated with 1.5-6mg daily experienced a 38 % increase in sperm count & 50% increase in sperm motility.
  Those with chronic fatigue, fibromyalgia, burstitis.
  Those with immune disorders of any kind.
  Those with asthma.
  Those with liver disorders.
  Women with abnormal PAP smears.
  Those with sleep/wake cycle disorders, or those with excessive sleepiness.
  Those with a family history of colon cancer.
  Those with vitiligo.
  Those with chronic myelogenous leukemia have overall increased cobalamin levels, but a decreased proportion of methylcobalamin compared to normals. The lower the proportion of MeCb, the worse the prognosis, the higher the proportion the better the prognosis. ( Also MeCb improved the survival time in leukemic mice).
  The form used in the above research varied between injectable & sublingual, but all was with methylcobalamin. All was in the dose range of 1-6 mg daily. Remember these vitamins are usually listed as micrograms, so would take 1000 mcg to make 1 mg. Research doses of folic acid have ranged from 1-20 mg/daily.
 


until next time,
Peace, Love & Health...
Priscilla Slagle M.D.
 
“May the thread of my song be not cut before my life merges in the sea of love”
    --from God Makes The Rivers To Flow
 
 
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