Glutamate, The Caffeine Gene, and the World Parkinson's Congress

What are we learning about glutamate and Parkinson's disease?



There's good news



For years we've been asking restaurants to omit the MSG because we get funky headaches later after eating foods containing this excitotoxin. We'v been reading food labels to avoid monosodium glutamate.  We were already working on an article about glutamate and the role this protein building amino acid and neurotransmitter plays in Parkinson's disease. We learned a little about the good, the bad and the ugly in the process. 

We know that glutamate is a rapid, excitatory transmitter and that it can be associated to a vulnerability to addiction, so perhaps you could call it the smoker's nemesis.  We also know that glutamate receptors are necessary for proper central nervous system functioning, for important cognitive function including memory formation and learning.

This week everyone is talking about glutamate and GRIN2A because of the news from the World Parkinson's Congress currently being held in Glasgow, Scotland.

The coffee cups are waiting 

It has been learned that GRIN2A, is the "coffee" gene which when combined with caffeine intake appears not only to be neuroprotective for PD in a certain percentage of the population but may also affect PD clinical trial results when some study participants may have the altered GRIN2A gene.  This in turn raises the question of whether it can also influence medications used to treat Parkinson's disease symptoms.

Those people protected by the caffeine gene are carriers of a specific variation of GRIN2A according to information discussed at the World Parkinson's Congress.  At this time the focus is on a limited population.

We already know from the long Hawaii coffee study that people who had regular caffeine intake were (48%-84%) less likely to develop Parkinson's disease. It would be more than interesting to know how many members of this study also had the special GRIN2A gene version. But that was then and we didn't have the same technology or gene bank.

GRIN2A is a glutamate NMDA subunit receptor in a class of ionotropic glutamate gated ion channels, permeable to calcium. There has already been research about Bipolar disorder, ADHD and Huntington's disease as well as Parkinson's disease in connection to a hypoglutaminergic condition being involved in the pathogenesis.  And certainly the negative role of glutamate in Parkinson's development is not unknown.

Researchers have been looking at the GRINB2 subunits for many years and their connection to PD in the forms of selective antagonists which can exacerbate levodopa-induced dyskinesia in animal models. In other animal studies it was discovered that loss of striatal dopamine led to an increased stimulation of NR2B aka GRIN2B which contains NMDA receptors.

Basically glutamate becomes a link in the nitric oxide chain.  Under certain conditions glutamate can break through the outer cell membrane via the NMDA (n-methyl-d-asparatate) receptors located on the neurons.  This creates a breach through which calcium can enter the cell.  We already know that calcium is implicated in the death of dopamine neurons. If this chain can be interrupted...

To read more about the 2010 World Parkinson's Congress and to see folksy photos, check out Talk Parkinson's. 

Additional reading:

Gene reference: GRIN2A 

Netherlands twin studies 

NMDA Receptors

Primate home range and GRIN2A

Is It True What They Say about Black Tea and PD?

Two Teas for Parkinson's disease

In recent years, I've been concentrating on my Green Tea intake because that's been the tea du jour. The ad man's darling. And certainly not without merit. Green tea has antioxidants which can possibly help PD by providing symptom relief or slowing progression. It has not been established that the green tea antioxidants are that readily available in tea form, however.

About antioxidant threatment, there isn't enough research to be definitive. There were CoQ10 studies but they have been flawed. Even the current studies are deficient because they do not include high enough doses.

There is a clinical trial now in Phase 2 in Beijing to determine if Green Tea is an effective & safe treatment for new PD patients without taking any other meds. The jury is still out and certainly the processing is important which may be why the studies are taking place in China.

We know that another constituent of tea, caffeine, is effective in delaying the onset of Parkinson's. That has already been established. And even if caffeine won't prevent PD, we're all for delaying the start time There have been caffeine studies, especially the 30+ year Hawaiian study which demonstrated a delayed onset. Tea contains more caffeine than coffee - put down that tea pot - until you brew it when it dilutes to about 2/5 less than coffee.

Green tea is made in such a way that chemically it is similar to the fresh leaf. Black tea is not a breed apart but actually the green tea leaves of the Camellia sinensis which have been completely fermented resulting in a slight reduction of caffeine and a change from the simple catechins (polyphenols) to the more complex theaflavins, theanine, an amino acid unique to tea leaves, and thearubigins.

Back in 2007 researchers in China collected data on more than 60,000 men and women in a study in which they determined that the polyphenols in green tea had an antioxidant effect which might protect neurons from the damaging effects of reactive oxygen species and nitric oxide. This has great implications for neuromotor diseases such as Parkinson's.

EGCG, Epigallocatechin Gallate, a catechin which functions as an antioxidant in green tea, converts to theaflavins and thearubigins in black teas. These can cross the the blood brain barrier and have been demonstrated to be effective against dementia in aging and AIDS related dementia plaques in a petri dish. They are now being further studied for their effectiveness in neurodegenerative diseases such as PD, AD, and HIV dementia.

What else about the black tea? Black tea is green tea which only contains about 3-10% of the polyphenols compared to 30-40% in green tea. There was a black tea study in 2008 in which it was said essentially that black tea showed an "inverse association" with Parkinson's disease risk that was not contradicted by the total caffeine intake or tobacco smoking. In other words the disease risk is actually reduced. The claim was that drinking a minimum of 23 cups of black tea a month might slow onset of PD by up to 71%

Tetley, a subsidiary of Tata Tea Ltd, is not going to be making any claims yet - they are probably still smarting over getting into hot water with the UK Advertising Standards Authority for overstating antioxidant health benefit claims.

For those of you who like milk with your cream but are concerned because you know that milk proteins could prevent the absorption of the flavonoids in your tea no worries. A Dutch study conducted a few years ago in which the total consumption was about 8 cups of tea a day. It demonstrated that the flavonoid bioavailability was not significantly affected by a bit of milk in your tea.

There's more to study about the components of green and black tea but for now, I'll enjoy my green and my black tea with milk and I think we'll be sending some black tea to our children.

Addendum 3/2012: I have read that taking mucuna puriens (the natural levodopa) with Epigallocatechin Gallate, ECGC, helps aid the transport efficiency and effectiveness.  We're ordering a green tea capsule high in EGCG to use with the curcuminoids and mucuna pruriens. We'll let you know. We'd like to lower the curcuminoid dosage as perhaps the MAOI side effects leave something to be desired.
Resources and Reading:
Green tea extracts may stop Parkinson's
Black tea may slash Parkinson's disease risk
Drinking Black Tea Reduces Risk of Parkinson's Disease
New Insights into Tea Ingredients
Theaflavins in Black Tea and Catechins in Green Tea Are Equally Effective Antioxidants
Tea Beverage
Steep it Loose
Destressing with L-theanine

A little help from Wikipedia:
Catechins
Thearubigin
Theanine

COFFEE,TEA, OR ME, A PARKINSONS PATIENT

I'm going for a cup of coffee, I'll be back soon to enter this blog.

Since 2000 a number of studies have indicated that drinking at least 100 mg of caffeine everyday might reduce the incidence of Parkinsons disease. 100 mg isn't much caffeine, about the amount in an espresso.

Studies show that men who drink no coffee at all are five times more likely to develop Parkinsons. Other tests demonstrated that caffeine protected mice from attempts to induce Parkinson's. In 2001 additional testing on mice at Massachusetts General Hospital by Michael Schwartzchild disclosed that caffeine appears to prevent the loss of dopamine, the depleted neurotransmitter in PD by rendering the A2A receptor inactive which seemed to prevent further deterioration.

Caffeine seems to help protect brain cells from Parkinsons disease, a disease that causes progressive speech and motor difficulties. Other sources of caffeine: teas, chocolate and cola drinks showed similar results.

Besides being a stimulant, caffeine has other effects. It blocks two receptors in the brain, one of which helps us go to sleep and the other as identified by different research has a role in inflammation and Parkinson's.

Why caffeine affects patients differently is unknown. Whether caffeine can slow the progression of PD as well as prevent it is also not known. In a very recent study from the Mayo Clinic 1208 subjects were studied for lifetime coffee drinking history. The study targeted two genes one of which encodes the caffeine receptor activity and the other the rate-limiting process of caffeine metabolism. The results of the study were inconclusive.

Another study shows that caffeine protects men from Parkinson's but not women. A study at Harvard School of Public Health showed that post menopausal women who took HRT (Hormone Replacement Therapy) and drank more than five cups of coffee a day were one and one half times more likely to develop Parkinsons than heavy coffee drinkers who weren't on HRT. Women who drank only a little coffee and took HRT were 65% less likely to develop Parkinsons.

There has been at least one study which demonstrated that women who have had both ovaries removed signficantly increased their chances of developing Parkinson's by 50%. There appears to be a link to natural estrogen as a protector.

A study by Tel Aviv University failed to show any neuroprotective effect from caffeine in men or women.

From the Journal of the American Medical Asociation comes the 30 year result of a Honolulu Heart Program study from 1965-68 of 8004 Japanese-American men. The conclusion was that the higher coffee (at least 28 oz a day) and caffeine consumption significantly reduced the incidence of age-related PD.

In a study at Duke University Movement Disorders Center it was determine that in families predisposed to have Parkinson's Disease, those who were serious coffee drinkers and also smoked appeared to be less likely to develop PD.

Looks like I picked the wrong year to cut down my coffee intake.

Sources: Science Express: Leiden University: October 2008
Scientific American 5-08-01 Health
Science Daily 4-10-07
JAMA 5-24-00