Parkinson's, B6, B12, and Folate - What's the Connection?
Kathrynne Holden, MS, RD
Copyright 2000

Ms. Holden is a registered dietitian specializing in Parkinson's
disease. She has published research, books, articles, and manuals on
nutrition and PD, including "Eat well, stay well with Parkinson's
disease." She moderates the NPF forum Ask the Parkinson Dietitian at:
www.parkinson.org

In the past decade, there has been increasing interest among
researchers about the effects of three B vitamins - B6, B12, and folate.
We now know that deficiencies occur with greater frequency than ever
suspected previously, particularly in older adults. We also now know
that deficiencies, if not corrected, can result in irreversible damage
in some people. Some health professionals are beginning to suspect that
these three vitamins may be significant factors in Parkinson's disease.

What are B6, B12, and folate, and what do they do?

These are essential nutrients, meaning that they are vital to life.
These three vitamins work both independently and together in many of the body's systems.

Vitamin B6 assists in making hormones, new proteins, and
neurotransmitters ("messengers" between nerve cells) for the body's use.
It also helps release stored sugar when we need it for fuel. It works
together with B12 and folate to remove homocysteine from the blood.
Homocysteine is a substance increasingly associated with a number of
diseases; more about this later.

Vitamin B12 plays a role in the synthesis of DNA, needed for formation
of new red blood cells. It takes part in the manufacture of the myelin
sheath - the protective coating that surrounds nerve cells. With B6 and
folate it removes homocysteine from the blood.

Folate, also called folacin or folic acid, is a partner with B12 in DNA
synthesis and in removal of homocysteine, and is required in many other
vital processes. Without folate, B12 would be unable to complete many of
its functions, and vice versa. Folate is the form found in foods, folic
acid is the form in dietary supplements.

How much do we need of these vitamins?

Nutrient needs are broken down by gender, age group, pregnancy, and
lactation. New guidelines have also established a Tolerable Upper Intake
Level. So, for example, while the RDA for vitamin B6 for males and
females age 19-30 years is 1.3 mg/day, the Tolerable Upper Intake Level
for both is 100 mg/day, making it easier to provide recommended amounts.


RDA* Tolerable Upper Intake Level ** +

Vitamin B6***+ 1.7 mg/day 100 mg/day (age 19 and older)

Vitamin B12+ 2.4 mcg/day Not Determined

Folate + 400 mcg/day 1000 mcg/day


Recommended Dietary Allowance
** The Tolerable Upper Intake Level is the maximum level of daily
nutrient intake that is likely to pose no risk of adverse effects, and
represents the total intake from food, water, and supplements.
*** Adults age 51 and older
+ not applicable if pregnant or lactating

Why do deficiencies occur, and what are signs of deficiencies?

Vitamin B6. Mild deficiencies of B6 are fairly common in the U.S.,
mostly because of dietary deficiencies, but sometimes due to use of
certain medications which interfere with B6, including hydralazine,
isoniazid, MAO inhibitors, penicillamine, and theophylline. (Conversely,
large amounts of B6 can interfere with the absorption of levodopa, an
important medication for Parkinson's disease. Current use of the
combinations of carbidopa-levodopa or benserazide-levodopa offset this
interaction for the most part; but use of supplements containing more
than 15 mg of B6 can overwhelm the protective effects of the carbidopa
and benserazide.)

Good food sources of B6 include chicken, fish, eggs, nuts and seeds,
dried beans and peas, soybeans, wheat germ, bananas, avocados, and
brewer's yeast. Also, some foods, including a number of breakfast
cereals, are fortified with B6.

Signs of B6 deficiency include irritability, depression, and confusion;
sore tongue, sores or ulcers of the mouth, and ulcers of the skin at the
corners of the mouth.

Vitamin B12. The human body stores this vitamin so well that it can
take a long time to deplete, sometimes several years. Nevertheless,
there are several reasons why people sometimes do experience deficiency. Animal foods are the only source of B12, therefore people who eat few or no animal products (meat, fish, poultry, eggs, milk) are at risk unless they use vitamin supplements.

Another problem is that B12 in foods cannot be absorbed by the body
until it is freed from the proteins in the food; the stomach produces an
acid that removes this protein. However, with age, we produce less and
less of this stomach acid. Many older adults don't produce enough acid
to allow them to absorb B12. Further, people who have acid reflux often
use medications that reduce stomach acid, which unfortunately also
decreases absorption of B12. Vitamin B12 is one of the few nutrients
that is better absorbed in pill form than from dietary sources.

Signs of B12 deficiency include numbness or a tingling "pins and
needles" sensation, or a burning feeling; a red, sore, or burning
tongue; loss of appetite; gait abnormalities, personality changes, an
Alzheimer-like dementia, psychosis, depression, and agitation,
particularly in older adults. Other signs are megaloblastic anemia, and
elevated serum homocysteine, in people of all ages. Researchers believe
that as many as 42% of people aged 65 and older may have some degree of B12 deficiency. Many people with PD are age 65 or older, and should be considered at risk and tested for B12 deficiency.

Folate. Folate is available in many foods: lima beans, brewer's yeast,
orange juice, dried beans, green peas, asparagus, beets, Brussels
sprouts, broccoli, corn, spinach and other dark green leafy vegetables,
soybeans, nuts and seeds. Further, the U.S. government requires that
food manufacturers fortify processed grain products with folic acid.
Yet, deficiencies of folate are not uncommon. This could be in part
because folate is another of the few nutrients in which the synthetic
form is absorbed much better (about 40 percent better) than the natural
form.

Because of the possibility of deficiency, women, including women with
PD, who are pregnant or wish to become pregnant are advised to take
supplements of folic acid; deficiencies can result in neural tube
defects in the unborn child.

Deficiencies of folate are also being increasingly studied for a
possible role in other diseases:

. A low intake of folic acid is associated with risk for colon cancer.
Chronic constipation, experienced by many people with PD, also increases
risk for colon cancer; it is prudent for those with PD to control
constipation and to be sure the diet is adequate in folate.

. A low level of folic acid in the blood is associated with higher
levels of serum homocysteine, a substance in the blood that may
contribute to heart disease, stroke, and dementias.

. Animal studies point to a link between low levels of folic acid and
Alzheimer's disease; and people with Alzheimer's are often found to have
low levels of folic acid. Some people with PD develop an Alzheimer-type
dementia. Again, prudence dictates consumption of adequate folate.

. Another study using mice found that folic acid deficiency led to
increased levels of homocysteine and symptoms of Parkinson's disease.
Researchers speculate that homocysteine may damage DNA in the substantia nigra, the area of the brain affected in Parkinson's disease.

. There are reports of improvement in restless leg syndrome (RLS) with
use of folate supplements; this has not as yet been studied thoroughly,
so it is too early to say whether there is a definite link. However,
people with PD often complain of RLS, and physicians should rule out the
possibility of folic acid deficiency.

Signs of folic acid deficiency include appetite loss, weight loss,
burning tongue, fatigue, weakness, shortness of breach, memory loss,
irritability, megaloblastic anemia, and increased levels of serum
homocysteine.

Should people with PD be concerned about these vitamins?

Although there are concerns, as mentioned above, that deserve further
study, it's too early to say definitely that these three vitamins are of
significance to people with PD. However, if you are over age 50 these
vitamins are of importance independently of PD. Furthermore, studies
have demonstrated that some people who use levodopa, considered the best medication for PD, develop elevated levels of serum homocysteine, due to the way in which the medication is metabolized. It is certainly a good idea to ask your doctor to test levels of serum homocysteine annually, and to check for signs of B vitamin deficiencies.

Should you take supplements?

There is growing agreement that older adults are at risk for nutrient
deficiency, whether PD is present or not, and that supplements can help.

. One study of older adults found that a multivitamin containing 100% of
the Daily Value improved low levels of several nutrients, including
vitamins B6, B12, and folate.

. A recent study in the United Kingdom suggests that folic acid intake
should be about three times that of the current recommendation for
elderly people.

. Other studies indicate that up to 10% of older adults with low-normal
levels of B12 are actually deficient and could benefit from supplements.
Because folate supplements can mask a B12 deficiency, it becomes extra
important to get enough B12 daily.

. The American Heart Association recommends a folate-rich diet to lower
homocysteine levels, and supplements of 2 mg B6, 400 mcg folic acid, and 6 mcg of B12 if dietary means are not sufficient to lower the
homocysteine.

For people with PD who use a medication that contains levodopa (such as
Sinemet, Madopar, Syndopa, Larodopa, etc.), you should be aware that
large amounts of vitamin B6 (more than 15 mg) can affect the absorption
of levodopa, by converting levodopa to dopamine in the stomach and
bloodstream. Dopamine cannot cross the blood-brain barrier, so it is
effectively blocked from its purpose.

Sinemet and Madopar contain either carbidopa or benserazide, which
"protect" the levodopa from B6; so ordinary supplements of B6 should not
be a problem for most people. However, very large amounts of B6, greater than 15 mg (and in sensitive persons, possibly as low as 10 mg), could overwhelm the protective effects of the carbidopa or benserazide. Such a supplement should be taken at bedtime with a light snack, or with meals at least two hours separately from levodopa.

In summary, older adults are acknowledged to be at increased risk for B
vitamin deficiencies. People with PD who are age 50 and over, therefore,
are at increased risk also. Whether younger people with PD should be
concerned about such deficiencies remains to be seen. A prudent and
rational approach for all those with PD is to:

. Discuss the possibility with their physicians, and to request tests
for B vitamin deficiencies

. Be aware of the signs of B vitamin deficiency

. Take a multivitamin/mineral supplement daily. Unless anemic, choose a
supplement that does not contain iron

. Take a B complex supplement if deficiencies occur; and take the
supplement separately from levodopa by at least two hours, preferably
with meals or a snack.

Knowledge is strength; awareness of dietary needs can prevent illness,
malnutrition, suffering, and hospitalization. If you have questions
about B vitamins or other nutrition or dietary needs, please visit the
National Parkinson Foundation website:

The above article may not be reproduced in any form except with
permission from the author.

References

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Kruman II, Kumaravel TS, Lohani A, Pedersen WA, Cutler RG, Kruman Y,
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homocysteine impair DNA repair in hippocampal neurons and sensitize them
to amyloid toxicity in experimental models of Alzheimer's disease. J
Neurosci 2002 Mar 1;22(5):1752-62.

Lobo A, Naso A, Arheart K, Kruger WD, Abou-Ghazala T, Alsous F, Nahlawi
M, Gupta A, Moustapha A, van Lente F, Jacobsen DW, Robinson K. Reduction
of homocysteine levels in coronary artery disease by low-dose folic acid
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Malinow, M.R. et al. Homocyst(e)ine, diet, and cardiovascular diseases:
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Muller T, Werne B, Fowler B, Kuhn W. Nigral endothelial dysfunction,
homocysteine, and Parkinson's disease. Lancet. 1999 Jul
10;354(9173):126-7.

Muller T, Woitalla D, Hauptmann B, Fowler B, Kuhn W. Decrease of
methionine and S-adenosylmethionine and increase of homocysteine in
treated patients with Parkinson's disease.
Neurosci Lett. 2001 Jul 27;308(1):54-6.

Naurath HJ, Joosten E, Riezler R, Stabler SP, Allen RH, Lindenbaum J.
Effects of vitamin B12, folate, and vitamin B6 supplements in elderly
people with normal serum vitamin concentrations. Lancet 1995; 346:85-89.

O'Keeffe ST. Restless legs syndrome. A review. Arch Intern Med.
1996;156:243-248.

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