The more homocysteine, the worse the Park... - Cure Parkinson's

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The more homocysteine, the worse the Parkinson's?

parkinsonshereandnow
parkinsonshereandnow

"You don't discover new continents if you don't have

the courage to lose sight of the old shores."

Andre Gide

An elevated level of the amino acid homocysteine in the blood is neurotoxic and has been reported as a truly important risk factor for developing Parkinson's, as well as cardiovascular disease and dementia in the general population (McCully 1969, Boushey 1995, Seshadri 2002). Homocysteine increases oxidative stress, compromises mitochondrial function, and ultimately leads to neuronal apoptosis or death. In addition, a strong link has been found between homocysteine and DNA damage and excitotoxicity. All of them with an essential role in neurodegeneration (Mattson 2002, Zoccolella 2006. Martignoni 2007).

As Dr. Pizzorno puts it so crushingly …"Because of its central role in sulfur and methyl group metabolism, elevated levels of homocysteine would be expected to negatively affect the biosynthesis of all of the following: SAMe, carnitine, chondroitin sulfates CoA, CoQlo, creatine, cysteine, dimethylglycine, epinephrine, glucosamine sulfate, glutathione, glycine, melatonh, pantethine, phosphatidylcholine, phosphatidylserine, serine, and taurine."

It is widely accepted that normal plasma Hcy levels range from 5-15 μM; moderate hyperhomocysteinemia 15- 30 μM; intermediate hyperhomocysteinemia 30-100 μM; severe hyperhomocysteinemia >100 μM (Tchantchou 2006).

A level above 20 micromoles/L, increases the risk of developing Parkinson's up to 8.64 times (Saadat 2018).

Parkinson's patients have high homocysteine and those taking levodopa even higher (Mattson 2003, Obeid 2007). Some authors claim that a high level is largely responsible for the current progression of the disease (Yasui 2000, Muller 2001). This seems so, so important to me, that I think it's worth reading several times...

It also crosses and damages the blood-brain barrier, which is responsible for protecting the brain (Beard 2011, Kanath 2006, Tyagi 2008). A supplement of vitamin B9 or folic acid (alone or with vitamins B6 and B12) has been shown to reduce the level of homocysteine (Reutens 2002, Siniscalchi 2005, Postuma 2006) and and also reduces damage to the aforementioned protective barrier (Kalani 2014).

A diet rich in vitamin B9 prevents Parkinson's by 49% (Religa 2006).

Neurologists such as Alhskog, Marjama-Lyons, Siniscalchi, González Maldonado, etc. recommend the use of B9 or the three B vitamins (B6, B9 and B12).

Already in 1998, Malinow published the very interesting results of his study. Fortification of cereals with 499 and 665 mg of folic acid,

increased vitamin B9 in the blood by 64.8% and 105.7%, respectively. And homocysteine decreased by 11.0% and 14.0% (Malinow 1998).

The use of folic acid is very well tolerated. Pregnant women are prescribed 400 mcg/day to prevent malformations in the fetus. Ahlskog recommends to its Parkinson patients 2 mg B9, 25 mg B6 and 2000 mcg (2 mg) B12 to control the levels of the dangerous homocysteine.

If Parkinson's could be seen as a parasitic plant that feeds on host roots, homocysteine would be one of the main root, if not the most important. And its "antidote" is something simple, cheap and safe (Nallamothu 2000): vitamin B9 or folic acid, folate... alone or together with vitamins B6 and B12.

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I would like to recall the work of two scientists.

The first one, the American pathologist Dr. Kilmer McCully, who was a pioneer in the investigation of the damage produced by high levels of homocysteine, especially to the cardiovascular system (1969) and who left us a surprising phrase: "Homocysteine is associated with more than a hundred diseases".

The second, to the Spanish neurologist Rafael González Maldonado, author of the book "Heterodox treatments in Parkinson's disease" (2004, 2013). He showed us already in those early dates the decisive importance of folic acid and homocysteine in Parkinson's disease. His book was key for my father and me. It has not yet been translated into English and other languages, despite being one of the most important books I know for patients and their families. One of the paradoxes of the Parkinson's world.

I reproduce it because you can see it all in Google Books.

It seems to me to be one of the most important pages written in these 203 years of modern Parkinson's history. Page 44 of "Heterodox treatments in Parkinson's disease", by the prestigious Spanish neurologist Rafael González Maldonado. In my opinion, one of the most important books that has been written about Parkinson's at any time and in any language (the most useful for me before and now, the one that helped me to wake up when I was "inside" the parkinsonian labyrinth). It was written in 2004 and revised in 2013, and should have been translated into every major language in the world by now. Another score to settle in the Parkinson's community.

«FOLIC ACID (VITAMIN B9).

It is necessary for the metabolism of nucleic acids and haemoglobin formation but folic acid ii has another very important function: to remove homocysteine from the blood, a substance that increases the risk of cardiovascular diseases, dementia and stroke, 734,1307 as well as Parkinson's, depression and 737 and even some cancers. 736 In adults, folic acid is neuroprotective, prevents physiological aging 732,735,736, and decreases the risk of Parkinson's. 290,737 Mice with Parkinson's MPTP make fewer dopaminergic lesions if they were given folic earlier. 290

To pregnant women i, the elderly ii and parkinsonians treated with levodopa should be given folic acid supplements.736,795 Levodopa increases homocysteine levels, which, in addition favouring other diseases is a possible cause of the progression of Parkinson's. 795,1278 Give folic acid supplements to Parkinsonians counteracts dangerous homocysteine and is a cheap and very recommended. 737,771,795

ii Older people often have elevated blood homocysteine that can be lowered with folic acid supplements.959».

Neurologist Dr. Rafael González Maldonado, "Tratamientos heterodoxos en la enfermedad de Parkinson", page 44.

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Controlling homocysteine with vitamin B9 is still a pending subject in the Parkinson's world. I think it would change the disease as we know it today. Another one of those paradoxes that is so difficult to explain.

WARNING: Despite the safety of folic acid or vitamin B9, it is always advisable to consult a neurologist in each case.

(by Jesus Marquez Rivera - Parkinson's here and now)

25 Replies

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Folate does reduce homocysteine but comes with a risk:

Folate Supplementation Carcinogenic

tinyurl.com/ycdrz5lj

Before supplementing with folate people should check their homocysteine levels first to see if it is actually necessary.

Good to know that homocysteine levels are increased by metabolites of levodopa.

I disagree with the statement that "normal plasma Hcy levels range from 5-15 μM". From my experience in the US normal range for Hcy is less than 10-11 depending on the lab. My doctor was concerned when 3 months ago my homocysteine jumped up to 14 after mostly being in single digits. I have MTHFR polymorphism which is supposedly to be quite common and therefore have to monitor levels of Hcy.

In order to keep it under control without putting yourself at risk for side effects it's good to distinguish between different forms of folate, see links:

mthfrsupport.com.au/2017/04...

mthfrsupport.com.au/2015/05...

cclemonade
cclemonade in reply to faridaro

I did not know there are different kinds of folate. Thank you.

Kia17
Kia17 in reply to cclemonade

See this: essendonnaturalhealth.com.a...

Kia17
Kia17 in reply to faridaro

Agree except that “Folinic acid cannot cross BBB. “

Folinic acid can cross the blood-brain barrier using the reduced folate carrier (RFC) when the FRα is blocked by FRAAs or non-functional due to mitochondrial dysfunction and/or genetic mutations.

Some people like myself with homozygous mthfr mutations are sensetive to 5-MTHF and methylated B12 but amazingly responsive to Folinic acid and Hydroxycobalamin.

faridaro
faridaro in reply to Kia17

That's good to know and to keep folinic acid in mind as an alternative to methylfolate. Apparently it depends on the individual, glad it's working for you, thanks for sharing!

Kia17
Kia17 in reply to faridaro

“How I beat my 10-year battle with anxiety after discovering folinic acid”

google.co.uk/amp/s/www.hera...

JBOVERT
JBOVERT in reply to faridaro

HI - I am wondering how much methyl foate to take and if 1400mcg dailey is to much

faridaro
faridaro in reply to JBOVERT

Jbovert, Unfortunately, I am not a medical practitioner and don't have experience with folate dosaging but would think the best way to know the appropriate dosage is to do a blood test first. The reference range for folate in the US is about 5-25 ng/mL. I've had 24.7 ng/mL on my last test while taking 400 mcg methylfolate daily as part of B-complex. However, if I would have less than 20 then would go on 1,000 mcg couple of times/week in addition to 400mcg /daily for 1-2 months to bring the levels up although I am not sure what the optimal range is. May be some people here have more knowledge/experience with this subject and provide some insights.

JBOVERT
JBOVERT in reply to faridaro

thanks for your info i really appreciate it... the problem is that i am not sure "where" to go look for the answer on my combo supplements methyl Cobalamin and the methyl folate any deas would help thanks again

rescuema
rescuema in reply to JBOVERT

It's actually best to take all B's since they work together. When not sure as in your case, take a good balanced methyl b complex such as Pure Encapsulation B Complex Plus.

faridaro
faridaro in reply to JBOVERT

I take B-complex plus by Pure Encapsulations which has high quality ingredients with the least amount of inactive ingredients. Rescuema is also in favor of this b complex.You can get it on amazon or at vitacost.

Thank you for another very informative post. You are giving me a jump ahead in my research.

Yes. I'm on your second post. Very helpful for my dad. Cheers to you.

Warning: before getting into vitamin B6, better check into this:

journeywithparkinsons.com/2...

Thanks for the link, Patrickk. We should also not forget that without vitamin B6 there is no dopamine, no matter how much levodopa we take.

Some neurologists like Ahlskog and the levodopa package leaflets put the safe limit at 25 mg, although it depends on the individual.

parkinsonhereandnow.blogspo...

The minimum daily requirement for B6 is 1.5 (one and one half) mg. Parkinson's patients by definition are producing less dopamine than normal -- therefore may not need a lot more B6, I would guess. Typical supplement for B6 seems to run about 100 mg for some reason.

rescuema
rescuema in reply to Patrickk

You might be interested in Park_bear's past B6 post below for more detail. No matter, it is very important not to be deficient in b6 (taken at least 2 hrs away from PD meds), along with b9 (often deficient in PWP) and b12 (sublingual best, b12 deficiency causes functional b9 deficiency).

healthunlocked.com/parkinso...

More on this

healthunlocked.com/parkinso...

sharoncrayn
sharoncrayn in reply to Patrickk

Some of his (Frank Church) comments are very debatable. Do your own due diligence.

Example: DDC is a gene not an enzyme; AADC , AAAD, and AAADC are the 3 enzymes which are needed. The DDC is the engineer for making these enzymes. However, it is the functional capacity of the pathway that is important! Dopamine is produced in a 2 step process along that pathway.

Ultimately, AADC, etc. converts L-dopa to dopamine by removing a carboxyl group (decarboxylation). The primary goal is to decarboxylate L-dopa to dopamine in the CNS, not the peripheral tissues where it cannot enter the brain, via inhibitors of these enzymes. Otherwise much of the dopamine is (can be) basically lost.

This construct is part of the classic, mainstream theory of PD. (the reduction of dopamine via the dysfunction of these enzymes, etc. ultimately causes the progression of PD).

Unfortunately, long term use of L-dopa can lead to L-dopa induced dyskinesia presumably due to elevated levels of homocysteine which is another theory.

Very intriguing, I'm going to have to dig into this... I'm wondering if there are implications for intervention and particularly with regard to stages of the disease. Of particular note to be tested is is the word " responsible," and"diet" and the question about what is a "normal" lab level of homocysteine, and the two variants of b6.

Very very interesting.

In terms of levels, this from ‘The End of Alzheimer’s’ by Dale Bredesen

GOAL: Homocysteine < 7 micromolar.

GOAL: Vitamin B12 = 500–1500 pg/ml; Folate = 10–25 ng/ml; Vitamin B6 = 60–100 mcg/L.

And he recommendeds the active forms of B6/B9/B12:

Pyridoxal-5-phosphate (P5P) is the active form of vitamin B6, methylcobalamin is an active form of vitamin B12, and methylfolate is an active form of vitamin B9.’

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I have MTHFR gene mutations which means folic acid is harmful for me and I need to take methyl folate.

YES I AGREE WITH JUST ABOUT ALL THAT YOU SAID EXCEPT THAT IT IS METHYL COBALIMIN VITAMIN B12 AND METHYL FOLATE B6 THAT WHEN COMBINED IN THE RESPECTIVE AMOUNTS OF B12 1000 MCG & 400 MCG FOR THE FOLATE...IS THE SOLUTION FOR MAJOR HOMOCYSTEINE INFESTATION...I KNOW THAT THIS IS TRUE BECAUSE N=MY HEART IS SATURATED WITH HOMOCYSTEINE AND I HAVE THOUGHT FOR YEARS THAT IT WAS CHOLESTEROL PLAQUE THAT WAS INSIDE MY ARTERIES UNTIL I ASKED THE CARDIOLOGIST WHO SAVED MY LIFE IN 2009 WHAT IT WAS AND HE TOLD ME HOMOCYSTEINE....IN 2006 I HAD CALCIUM SCORING DONE ON MY HEART AND SCORED 1500! SO I KIND OF THOUGHT THATSINCE I HAD BEEN TAKING A STATIN DRUG SINCE 1986 THAT I WAS IMMUNE FROM THIS HEART BLOCKAGE ISSUE..UNTIL THE CALCIUM SCORING 85% BOCKSGE IN MY PROXIMAL CIRCUMFLEX WHICH NOW HAS 3 STENTS IN IT... YES WELL THANK YOU FOR ENLIGHTENING ME ON THE OTHER ISSUES REGARDING HOMOSCYSTEINE AND PARKINSONS BY THE WAY I AM SUFFERING FROM'MSA IF YOU TALK TO ONE OF MY NEUROLOGISTS AND

PSP IF YOU TALK TO ANOTHER ONE....SO I AM WAITING FOR THE CLINICAL TRIALS FOR A NEW DRUG CALLED

RETROTOPE OR R001 AND ONCE THAT COMES OUT AND I CAN GET MY HANDS ON SOME OF THAT I BELIEVE THAT I CAN PUT ALL THIS BEHIND ME....BUT IN THE MEANTIME IAM WAITING FOR THE PANDEMIC TO

SETTLE DOWN SO THESE FOLKS WIL FEEL A LITTLE BIT

BETTER ABOUT CONDUCTING THE TRIAL! MY APOLOGIES FOR THE "CAPS" BUT I CAN SEE THE WORDS SO MUCH EASIER...NOW I AM GOING TO RE READ WHAT YOU SAID ABOVE..THANKS AGAIN

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