This is the information that gave us hope while my father was alive and has given hope to many since then (March 2012).

1. News that worried us.


In the coming decades the number of Parkinson's disease patients is feared to increase very worryingly, to double by 2030 (Dorsey 2007) and even to triple by 2050. We already know that between 1990 and 2015 the number of sick people worldwide has doubled (Dorsey 2018). And more and more young people and at younger ages (which would speak of a hostile environment: diet impoverished in key nutrients, environmental toxins, etc.). Worldwide, but especially in industrialized countries. They say that the main cause would be the aging of the population. Neither my father nor I were ever too satisfied with that explanation.

Every hour a case of Parkinson's disease is diagnosed in Spain. Every nine minutes, a new case in Europe and another in the United States.

Age is considered a risk factor. But the areas of the brain where neurons are lost show differences between the aging normal brain and the brain with Parkinson's disease: in the former, mainly in the dorsal regions of the substantia nigra and, in the case of Parkinson's, the loss in the latter occurs, in particular, in the ventral regions of the substantia nigra (Gibb 1994).

In addition, when the brain of a person with Parkinson's disease is autopsied, Lewy bodies usually appear in the substantia nigra. But they are also often found in the brains of people without Parkinson's disease. Therefore, it has been suggested that people with Parkinson's experience an accelerated aging process (Adams 1997). As the famous Dr. William Osler believed, a century earlier.

But I think it is in the same way that living in the countryside and drinking well water increase the risk of Parkinson's disease. The use of pesticides and other chemicals could be the cause (Barbeau 1987). I think it is not age, but lifestyle. Just as it is not the field or the well water, but the pesticides and other chemicals it contains.

It is clear from graphs in some books and studies that pineal melatonin production clearly declines with each decade of life (Wu 2005, Skene 2003) to less than 10 % of the amount produced in youth.

The lesions produced by the toxic MPTP increase with the age of the mice (Mandavilli 2000). Experimental parkinsonism does not occur with MPTP in young rats, as it does in old rats. Many other substances have a neuroprotective effect on the toxicant: magnesium (Oyanagi 2010), folic acid (Duan 2002), silymarin from milk thistle (Perez-H 2014; Jung 2014), etc.

The deterioration typical of natural ageing is confused with one that is
aggravated by multiple deficiencies (vitamin C, D, zinc, selenium, magnesium...) and an unnatural lifestyle (often due to external causes unrelated to the patients: environmental pollutants, medicines that cause Parkinsonism, etc.), which leads to the development of disease when levels of melatonin, coenzyme Q10 or glutathione are very low.
Aggressions are successful when neuroprotective defences are very low (fifth and sixth decades of life). However, when the aggressive factors are very strong and/or the defences are weakened by genes or deficiencies, Parkinson's disease manifests itself much earlier.


2. Studies that gave us hope.

"The father of the disease could have been anyone,
but there is no doubt that the mother was bad diet".
Ancient Chinese proverb


A) Foods and suplements.

What struck us most was that simply drinking COFFEE regularly (about two cups a day) had such surprising neuroprotective effects against Parkinson's disease:

- a lower risk of suffering from it, between 20 and 70 % .
- in case of developing it, it will appear on average 8 years later, from 64 to 72.
- not consuming coffee increases the risk five times.

Caffeine for many reasons, in addition to its resemblance to iron chelators, for its vasoconstrictor capacity of the blood-brain barrier. Perhaps by forming a cocktail with other substances such as nicotinic acid, ferulic acid, phytomelatonin...

(Benedetti 2000, Sobel 2000, Hu 2007, Saaksjarvi 2008).

Studies with identical twins gave us a lot of hope, since despite sharing the same genes, one can have the disease and the other cannot. It is known that lifestyle (EPIGENETICS), influences whether genes will be "expressed" or "silenced". These studies on smoking (Tanner 2002) and on the consumption of antioxidant vitamins (Maher 2002) also revealed that both can prevent or delay the development of the disease (in the twin who smoked or in the twin who took vitamin supplements - up to 3.2 years). This is confirmed by the finding that vitamin B12 epigenetically regulates-silences-the major gene for so-called familial or hereditary Parkinson's: the LRRK2 (Schaffner 2019).

The regions of the planet where GREEN TEA is consumed have half the cases of Parkinson's disease (Pan 2003). If the disease is present, it delays its onset by 7.7 years (Kandinov 2009). The main polyphenol it contains, epigallocatechin gallate (EGCG), prevents the death of neurons, rescues the damaged ones and neutralizes the alteration of the alpha-synuclein protein (Mandel 2004, 2008, 2011, 2012, Levites 2003), among many other beneficial properties, being considered as effective in the prevention and treatment of the disease (Li 2006; Ramassamy 2006; Guo 2007; Avramovich-Tirosh 2007; Zhao 2009).

VITAMIN D3 (cholecalciferol) is able to prevent Parkinson's disease by 67% in certain patients (Knekt 2010). It even seems to have the property of slowing down the progression of the disease, with doses of 1200 IU daily for one year (Suzuki 2013). Several neurologists recommend or use between 5,000 and 10,000 IU: Perlmutter 2013, Coimbra, Hiller 2018, Fullard and Duda 2020... During 30 minutes of sunbathing on the beach, the body synthesises approximately 10,000-25,000 IU (Fullard 2020). It also regulates the expression of the gene controlling the neurotrophic factor GDNF (Naveilhan 1996, Verity 1999, Luong 2012). Administration of this factor could be one of the most promising treatments in Neurology today (Gill 2003, 2005, Slevin 2005, Patel and Gill 2007, 2013). After patent problems, Dr. Steven S. Gill has resumed research in 2013.

Intense PHYSICAL EXERCISE on an exercise bike (especially forced exercise performed in tandem with a healthy person) provides an improvement in motor symptoms of around 35-40 %, similar to a dose of levodopa (Alberts 2011). Physical exercise also promotes neuroplasticity and neurogenesis (Mattson 2000). It can even delay the onset of symptoms (Tsai 2002) and, slow down and stop the progression of the disease (Oguh 2014). In short, it improves virtually everything: motor (Prodoehl 2015, David 2016, Chung 2016, Bhalsing 2018) and non-motor symptoms (David 2015, Reynolds 2016).

In a study conducted in Japan, depending on the level of MAGNESIUM that the mice had in their blood it was possible or not to produce experimental parkinsonism with the known toxic MPTP. For those with a high level, it was impossible to cause the disease (Oyanagi 2010). Magnesium is known to be neuroprotective (Vink 2009, Durlach 1997, Wallach 1994, Held 2002) and also protects against heavy metal and aluminum damage (Yasui 1992). It also participates in the synthesis of dopamine and glutathione. It also inhibits the aggregation of spontaneous alpha-synuclein and that produced by iron (Golts 2002).

Magnesium concentration in Parkinson's patients is low. A relationship has been observed between the magnesium level and the duration and severity of the disease (Barbiroli 1999). There is even talk of "magnesoma" (Piovesan 2012), because of its importance on proteins and epigenetics (the study of what causes genes to be expressed or silenced, simply put).

An elevated level of the amino acid HOMOCYSTEINE in the blood is neurotoxic and has been identified as a risk factor for developing the disease. 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 more so (Mattson 2003, Obeid 2007). Some authors claim that an elevated level is largely responsible for the current progression of the disease (Yasui 2000, Muller 2001). It also damages the blood-brain barrier, which is responsible for protecting the brain (Beard 2011, Kanath 2006, Tyagi 2008). With a supplementation of vitamin B9 or folic acid (alone or with vitamins B6 and B12) it has been shown to reduce the level of homocysteine (Postuma 2002, Reutens 2002) and the damage to the aforementioned protective barrier (Kalani 2014). The famous neurologist Ahlskog recommends in his books: 2 mg B9, 25 mg B6 and 2000 mcg (2 mg) B12 to its Parkinson's patients to control levels of the dangerous homocysteine.

GLUTATHIONE is one of the most potent antioxidants and, in its intravenous (IV) form, the one with the most spectacular result I have ever seen in some Parkinson's patients. Neurologist David Perlmutter is perhaps the best known of the physicians applying this therapy. The videos available on the Internet are invaluable in bringing hope to patients and their families. A study in which Dr. Perlmutter participated in 2009 yields less spectacular results on intravenous glutathione therapy (Hauser 2009).

In 1982 a study appeared entitled "Parkinson's disease: a disorder due to glutathione deficiency in the substantia nigra?" (Perry 1982). It seems that Parkinson's patients have very low levels of glutathione in the brain (Arakawa 2007) and that it would be related to the severity of symptoms (Sechi 1996). Sian (1994) found only 40% glutathione in the substantia nigra of Parkinson's patients. In advanced stages of the disease, the level of reduced (active) glutathione could be as low as 2% of normal (Adams 1991).

Hardly anyone questions the importance of glutathione in Parkinson's disease. The debate arises as to how to administer it effectively to raise the concentration in neurons to normal levels.

By administering sustained-release vitamins B6, B9 and B12, it would be possible for glutathione and vitamin B6 to be administered without interfering with levodopa (Lewis 2002). There are researchers who propose precursors such as N-acetyl-cysteine or NAC (Schapira 1990, Martinez 1999, Shahripour 2014, Monti 2019), which cross the blood-brain barrier more easily or substances that restore the glutathione level inside cells (alpha lipoic acid, silymarin from milk thistle, melatonin, turmeric, vitamin C). The neuroprotective ability of the drug selegiline is due to the fact that it somewhat elevates glutathione (Tanaka 2002).

During the 18 years of my father's illness and the first two years of preparing this project (i.e., I needed 20 years!), I did not realize the extraordinary value, the indispensable role, of VITAMIN C in everything related to Parkinson's: synthesis of dopamine (Seitz 1998) and carnitine (Jacob 1997), "recycling" to its useful forms of vitamin E (Halpner 1998), glutathione (Henning 1991) and flavonoids (Jacob 1997), synthesis of serotonin and melatonin, norepinephrine and epinephrine....

In addition, a diet rich in vitamin C reduces the risk of Parkinson's, while one poor in the vitamin increases it (Cerhan 1994, Singh 1995, De Rijk 1997). It is recommended in the early (Seitz 1998) and late stages (Linazasoro 1995). In addition numerous researchers indicate that it protects neurons from residual levodopa-dopamine damage (Riederer 1989, Pardo 1993, Berg 2001...) In the article "Vitamin C and Parkinson's, essential to prevent and treat this disease?", published in my personal blog, you can expand on this truly "transformative" information: without sufficient vitamin C there cannot be enough dopa or much else.

In recent years we have received three "treasures" that have revolutionised or should revolutionise forever the Parkinsonian "triad": disease, treatments and the world around the patient (labyrinth, jungle):

1) VITAMIN B1 (thiamine hydrochloride): About 4 grams per day on average, divided into two oral intakes, with similar efficacy to intramuscular, easier and safer (Smithline 2012). Results of the Costantini 2013 neurological study: 31-77% motor and non-motor improvement (UPDRS scale). Or 100 mg intramuscularly, twice a week (Smithline 2012, Luong and Nguyen 2013, Costantini and Fancellu 2013, 2015).

2) VITAMIN B2 (riboflavin): 90 mg daily, divided into three doses (30-30-30). Despite some "flaws" in the study, motor improvements of 44-71% between 3 and 6 months. Three of the participants, 100 % improvement - Hoehn & Yahr scale - (Coimbra 2003, Marashly 2017). 200 and 400 mg were used to treat migraines in children and adults with success and without adverse effects (Schoenen 1994, 1998, 1999).

3) VITAMIN B12 (cobalamin): as with vitamin B1, high doses of 500-2000 mcg/day orally overcome the body's obstacles (including the lack of intrinsic factor in the stomach: Albadal 2005). B12 modulates the main "hereditary" Parkinson's gene, LRRK2 (Schaffner 2019); inhibits alpha-synuclein (Jia 2019); slows Parkinson's progression, symptoms such as freezing, gait and postural instability are worse with lower B12 and non-motor, cognitive ones - especially depending on homocysteine level (Christine 2018); is related to symptom severity (McCarter 2019) as well as a lower risk of dementia (Christine 2018, McCarter 2020), etc.

4) VITAMIN D3 (cholecalciferol). Vitamin D is able to prevent Parkinson's disease by 67% in certain patients (Knekt 2010). It even appears to have the property of slowing down the progression of the disease, with doses of 1200 IU daily for one year, no worsening according to UPDRS scale (Suzuki 2013). It also regulates the expression of the gene controlling the neurotrophic factor GDNF (Naveilhan 1996, Verity 1999, Luong 2012). Administration of this factor could be one of the most promising treatments in neurology today (Gill 2003, 2005, Slevin 2005, Patel and Gill 2007, 2013). After patent problems, Dr. Steven S. Gill has resumed research in 2013.

Between 5000 and 10,000 IU daily, recommended or used in studies by these neurologists (Perlmutter 2013, Coimbra "Protocol", Hiller 2018, Fullard and Duda 2020). During 30 minutes of sunbathing on the beach, the body synthesises approximately 10,000-25,000 IU (Fullard 2020).

And in the same sense there are hundreds, thousands of studies: melatonin, nicotine patches, NADH IV, coenzyme Q10, complete vitamin E (tocopherols and tocotrienols), each and every vitamin of the B group, oxidised vitamin C or dehydroascorbic acid, selenium, zinc, creatine, carnitine, omega 3 EPA and DHA, flavonoids, turmeric and an endless etcetera.

FINAL THOUGHTS:

Over the last few years, I have had a growing intuition that there is so much more waiting out there. The keys to solving the mystery of Parkinson's disease. That is why I am still looking for a publisher or a patron who will allow me to continue on this path all the time until I reach my goal: to find those who have checkmated Parkinson's, as patients (Annetta Freeman) or as researchers or doctors (Costantini, Coimbra, Birkmayer, Phillipson, Hinz's studies rather than his protocol...).
Thousands of studies and hundreds of books contain valuable information that still sleeps in the limbo of bookshelves and databases...

***

Forthcoming works and book projects.

B) Nature: medicinal plants and mushrooms...
C) The wisdom of the East: Ayurveda, Traditional Chinese Medicine...


Moral.

As in children's stories and fables, we can draw wise lessons for life.

I have read that the precursor NAC combined with Glycine is more effective than taking even liposomal Glutathione. The latter is easily broken down into its constituent parts.
In addition the combination has found its way into the longevity community.

Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial - PubMed

New NAC & Glutathione Paper Shows 24% Lifespan Extension - YouTube

Thanks again for wonderful content.