This coming Monday (if everything goes as planned) I will publish on my blog "Parkinson's here and now" the link to a free book of about 250-300 pages and in printable pdf format, which collects the most interesting of the book I published in 2015 (now translated into English) as a tribute to my father and the most read and commented of what has been published in blogs, forums and social networks in recent years.
I think the book offers a coherent vision and with sufficient backing in scientific studies on the fact that we could already decisively improve the lives of the sick and family members. WE ALREADY KNOW ENOUGH FOR THAT. Mainly from those who are beginning this hard road, but also from those who have already been on medication and iatrogenic for many years.
I have learned and am learning so much in this forum that I wanted to advance you all a passage as a thank you and also to give it publicity and facilitate its dissemination. I sincerely believe it may help many people to see it all differently, but concentrated in a few hundred pages. And thus fulfill in part the promise I made to my father:
"My son, write about all this. May no one else have to go through what I went through. I did not understand anything and I realized it too late. Make that what we have lived and learned in these years has not been useless... that it will not be lost. Promise me that you will not leave them alone" (January-February 2012).
"Parkinson's here and now. 27 years searching for a cure for Parkinson's disease (1994-2021).", pages 13-20.
NEWS THAT WORRY US AND STUDIES THAT GIVE US HOPE.
Note: Although this is not a scientific book, it includes brief references to studies that helped my father and me to advance in the understanding and care of his disease and also in the preparation of this project. We interpret them according to the state of our knowledge and experience at the time and with all our limitations, but I believe they can shed light on our evolution from fear to hope.
News that worry us.
In the coming decades the number of Parkinson's disease sufferers 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.
Studies that give 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
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 link 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, in simplified terms).
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).
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 and dopamine.
In recent years we have received three treasures that have revolutionized or should forever revolutionize 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.
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, vitamin C, selenium, zinc, creatine, carnitine, omega 3 EPA and DHA, flavonoids, turmeric and an endless etcetera.
Glycine and N-acetylcysteine (GlyNAC) supplementation?
