"If the book we're reading doesn't wake us up with a blow to the head, what are we reading for?… A book must be the axe for the frozen sea within us."
Franz Kafka


Introduction.

Could vitamin C be an essential element in current and future Parkinson's treatments?

Did you know that vitamin C is essential in the chain of synthesis of phenylalanine - tyrosine - DOPA - dopamine - norepinephrine (noradrenaline)? And that there are surprising studies on the potential of foods rich in this vitamin to prevent and improve the quality of life of Parkinsonians?

The current figures for Parkinson's disease are very troubling. The forecasts for the coming decades are typical of a "pandemic" (Dorsey 2007, 2018). Vitamin C has been a great unknown to the Parkinson's world for many years. Books dealing with the disease do not usually mention the vitamin. And those about the vitamin avoid mentioning Parkinson's disease. As if it were a taboo. As if there were no reasons to use it and studies supporting such uses (tyrosine, precursor of dopa; carnitine, mitochondria and energy; collagen and integrity of the blood-brain barrier; regeneration of glutathione, vitamin E and flavonoids; less oxidation of levodopa remnants; fascinating redox system dehydroascorbic acid-gluthione, using the oxidized form to enter the brain, cells and mitochondria, etc.).

Parkinson's Disease increasingly seems to me a kind of multicarencial syndrome, as well as multifactorial (Cawein 1970; Karobath 1971; Charlton 1992, 1997; Hinz 2011, 2016), in which vitamin C could play a surprising role in its causes and development, as well as in future treatments.



1. The initial surprise about the importance of this vitamin, so little known in relation to Parkinson's disease.

If someone had told me years ago that a diet rich in vitamin C prevented Parkinson's and that a vitamin C deficiency increased the risk of Parkinson's disease, I wouldn't have taken it seriously or it would have been incomprehensible. I didn't understand that there could be anything other than medication and other official treatments.

When I started having a relationship with Parkinson's about 25 years ago (because of my father's diagnosis in 1994), I couldn't even suspect something like that.

But the most worrying thing is that 18 years later, after my father's death in 2012, the important role of vitamin C remained unclear, despite numerous favourable and some unfavourable studies.

I had to spend three years preparing a book to awaken to this reality which is before our eyes, but which we do not usually see.

Today I began to see the problem from different points of view, being the nutritional the most important.

Two exceptional books were largely responsible for that slow and costly process of changing our mentalities. In them, the authors mentioned and commented on several studies that forever changed our view of Parkinson's disease and possible complementary or alternative treatments (especially in terms of prevention and reduction of the adverse effects of medication, with the consequent improvement in the quality of life of patients and their families):


The first was "Tratamientos heterodoxos en la enfermedad de Parkinson" (Heterodox treatments in Parkinson's disease), by neurologist Dr. Rafael González Maldonado. The most important book we had at our disposal in those years and even today. I find it incomprehensible that it has not yet been translated into English. In this book we discovered the study of the famous neurologist Stanley Fahn, from 1992, in which he reached very revealing conclusions about the use of vitamin C and E supplements (3000 mg and 3200 IU, respectively), with which he managed to delay the start of the usual Parkinson's medication by 2.5 years (agonists or levodopa with inhibitors).

The second was "Textbook of Nutritional Medicine", by Dr. Melvyn Werbach. In this work, chapter 16, dedicated to Parkinson's, mentioned a series of studies that were conducted in the 1990s, in which its authors (Cerhan 1994, Singh 1995, De Rijk 1997) found that a diet rich in vitamin C reduced the risk of Parkinson's and that a diet poor in this vitamin, increased it. In the later sections of this article, we will check the reasons and studies that support the direct relationship between the consumption of vitamin C, either in foods or supplements, and different aspects of the disease.

What we barely understood then became clearer later, especially when we learned that dopamine needs ascorbate (vitamin C) to make its synthesis from tyrosine and the active form of vitamin B6 from dopa.

WITHOUT VITAMIN C SUFFICIENT, THERE CANNOT BE SO MUCH DOPAMIN nor a very long etcetera of substances that form the more than 300 or 400 biological reactions in which this vitamin participates.

More and more studies continue to appear, as well as new properties of vitamin C:

- its epigenetic potential (Young 2015; Guz 2017);
- its production in small quantities in the intestinal flora (LeBlanc 2013);
- its role in the neurogenesis of the adult human brain (Oyarce 2014);
- the relationship between scurvy and a type of Parkinsonism (Noble 2013, Quiroga 2014).
- scurvy would not only be a product of a food deficiency, but there would be a greater propensity according to certain genetic characteristics (Delanghe 2007).



2. The functions of vitamin C and its possible direct relationship with Parkinson's disease.


Due to the comments of the authors cited above, the search began for the reasons why a rich diet reduced the risk of developing Parkinson's and a deficient diet increased it.

Knowing some of the functions of vitamin C, it seemed possible to us its direct relationship with the causes, prevention and treatment of Parkinson's disease.

In books and articles by specialists in nutrition and vitamins we found very revealing information about health and, specifically, about some aspects of what we were learning about Parkinson's disease:

1. The main function of vitamin C is the prevention of its deficiency disease, scurvy. As well as avoiding the disorders produced by a deficiency not so serious as to produce scurvy (subclinical). Hospital studies often show levels of scurvy and subclinical deficiency among those admitted, especially the elderly (Gan 2008, Raynaud-Simon 2010) and more frequent in the developed world than we think (Smith 2011, Callus 2018).

2. Essential in the synthesis of collagen, hydroxylation of the amino acids lysine and proline (Ernglad 1986). The hematoencephalic barrier (protective of the brain), is based on a narrowing of the capillaries and on the good state of the internal covering of the blood vessels (endothelium), which depend on the good state of the collagen. The most obvious symptom of scurvy is generalised bleeding in the body due to the impossibility or difficulty of forming collagen.

3. Vitamin C is a vital, water-soluble antioxidant (in addition, it "recycles" vitamin E, flavonoids and glutathione, so important in Parkinson's). Excessive oxidation (by free radicals) is one of the most accepted hypotheses about the cause of this disease. Without enough vitamin C, the brain is defenceless against the oxidation of the remnants of dopamine.

Vitamin C participates in redox reactions (recovery of oxidized forms to those reduced or useful for the body):

Vitamin C is essential in everything related to glutathione. With a low level of this vitamin, reduced glutathione (GSH) and oxidized glutathione (GSSG), as well as the relationship between both, are low (Henning, 1991). Vitamin C regenerates vitamin E (Halpner, 1998). And it also recycles flavonoids (Jacob 1997). One study has shown its ability to prevent Parkinson's by 40%. (Gao 2012)

4. Vitamin C is essential in the synthesis of carnitine, the substance necessary for cells to transform fat into energy (in the mitochondria). Lack of energy is one of the main symptoms of Parkinson's... and also of scurvy. Carnitine is neuroprotective (Jacob 1997, Rebouche 1995).


5. Vitamin C is part of the metabolism of tyrosine, an amino acid that is a precursor to dopa and dopamine, the neurotransmitter that Parkinson's patients lack (but not only).

Norepinephrine (noradrenaline) needs ascorbate (vitamin C) to be synthesized from dopamine.

The body requires vitamin C, magnesium and some B vitamins for the conversion of tryptophan into serotonin (serotonin is also a precursor of the famous melatonin, the hormone that regulates sleep and a powerful antioxidant).


6. It is involved in the formation of glial cells (90 % of those in the brain, which in certain circumstances become neurons) and in the synthesis of the myelin covering the nerves (Englard 1986, Katsuki 1996).


7. Essential in microsomal metabolism (detoxifying function of the liver). Neurologists Jean Lombard and Jill Marjama-Lyons advise milk thistle silymarin for those taking levodopa (metabolized in the liver). Silymarin regenerates the liver (used to recover liver damaged by poisonous mushrooms).

8. It regulates cholesterol (it transforms it into bile acids); it strengthens the immune system which interacts with the central nervous system (Rabin 1989); it reduces the release of histamine (allergic reactions) and increases its degradation in hydantoin, etc.


9. Essential for the synthesis of vitamin D, through the two successive hydroxylation processes that take place in the liver and in the kidneys and which are impossible without ascorbate or vitamin C (Cantatore 1992).



3. What the studies affirm and nobody told us.


In addition to observing the critical functions of vitamin C in our health and the reasonable relationship that we establish from them with Parkinson's, there are numerous important studies that confirm those links.

The vision of these studies gathered in a list allows us to understand the true dimension of this vitamin in many aspects of the disease:

- A diet rich in vitamin C reduces the risk of Parkinson's, while a diet poor in vitamin C increases the risk of Parkinson's (Cerhan 1994, Singh 1995, De Rijk 1997).

- It stimulates the production of dopamine, participates in the metabolism of tyrosine, the precursor of dopa, and this of dopamine, and finally in the conversion of dopamine into norepinephrine (Seitz 1998).

- It is recommended in the initial stages of the disease (Seitz 1998) and also in the advanced stages (Linazasoro 1995). It seems to improve the state of the patients: speech, writing, mobility of the head, less salivation (Sacks 1975). This was a 62-year-old patient and each time he replaced vitamin C with a placebo, the patient worsened and improved again when the vitamin was restored (without the patient knowing it).

- It reduces the toxicity of levodopa (Pardo 1993, Berg 2001, Riederer 1989, Florence 1988, Offen 1996).

- It reduces damage to blood vessels by hyperhomocysteinemia (Krajkovicova 2002). The amino acid homocysteine is also neurotoxic. Parkinson's patients often have high levels. Levodopa raises them higher. In addition, vitamin C activates folate (vitamin B9), which is mainly responsible, together with vitamins B6 and B12, for the reduction of homocysteine levels (Postuma 2006, Reutens 2002).


The role of vitamin C in the synthesis of carnitine, in the synthesis of serotonin and in the recovery of useful forms of vitamin E, flavonoids and glutathione, further multiply its value. the selection of a few studies among the many available will not give an idea of its critical importance:



CARNITINE. It has neuroprotective capacity against known parkinsonizing toxics, such as MPTP.

MELATONINE. Doctor Acuña Castroviejo and his team have carried out numerous studies and advise Parkinson's patients. It is a powerful endogenous antioxidant (synthesized by the body), but whose production is reduced over the years, making the brain more vulnerable. It seems particularly effective in dyskinesias induced by levodopa.

VITAMIN E. Despite the prestigious DATATOP study (conducted with only one part of vitamin E, alpha-tocopherol), which found no evidence of the protective capacity of vitamin E in the form of a Parkinson's supplement, there are studies to the contrary. No one questions the neuroprotective capacity of vitamin E in foods (it is now known that this is mainly due to tocotrienols). A diet rich in vitamin C and E prevents disease (Martin 2002).

Studies by Fahn and Martin seem to indicate that foods and supplements have much the same bioavailability and efficacy. In vitamin C it is clear (ascorbic acid is the same), in E not so much (normally only alpha-tocopherol, without tocotrienols, is used in supplements and studies).

FLAVONOIDS. A Harvard study links a sufficient intake of flavonoids with up to 40% less risk of developing Parkinson's (Gao 2012).

GLUTATHIONE. The health and Parkinson's disease properties of reduced glutathione have been confirmed by numerous studies. When the level of vitamin C is low, the level of reduced glutathione is also low. In Parkinson's patients there is only 50% glutathione in the substantia nigra, and in advanced stages only 2%.

VITAMIN D. It prevents Parkinson's by 67% in certain cases (Knekt 2010). it even slows down the progression of the disease, with doses of 1200 IU daily for one year (Suzuki 2013). It also regulates the expression of the gene that controls the famous neurotrophic factor GDNF (Naveilhan 1996, Verity 1999, Luong 2012), etc, etc.

DEHYDROASCORBIC ACID (oxidized and reversible form of ascorbic acid).

Could the oxidized form of vitamin C in Parkinson's be of extraordinary importance? In order to cross the blood-brain barrier, the cell membrane and enter the mitochondria, ascorbic acid oxidizes to the form of dehydroascorbic acid (which can cross it as if it were glucose - it uses the same transporters) and, once inside, glutathione helps this oxidized vitamin C return to its normal (reduced) form and can act as an antioxidant in the brain and mitochondria (Crook 1941, Deverenkov 2018, Ahule 2019). It seems likely that a very low level of glutathione will hinder this recovery of vitamin C to its reduced or active form, progressively preventing its antioxidant activity in the brain and mitochondria as the disease progresses.

FOLATE (VITAMIN B9). This vitamin has many essential functions, but perhaps the most interesting is its ability to regulate the level of dangerous homocysteine. Vitamin C "activates" folate and reduces vascular damage from high homocysteine levels.



4. What a "simple" vitamin can teach us.

So many years we were lost and hopeless in the "parkinsonian labyrinth" that when we were able to reach conclusions like the next one, we regained some hope. For my father it was too late, but I trust that many patients do not need all the time that a neurodegenerative disease lasts to learn some essential things, as happened to us.

If there isn't enough vitamin C, there can't be enough dopamine, or carnitine, or norepinephrine, or reduced glutathione (the useful form), or serotonin. Motor problems, tremors, fatigue, insomnia or depression will be normal with these deficiencies.

What would happen if a newly diagnosed patient was given foods rich in vitamin C, flavonoids, vitamin E, vitamins B3, B6 and B9, green tea, coffee, vitamin D, silymarin, etc., in the amount to be determined by his neurologist, waiting to delay as much as possible the need for medication or take the smallest doses if necessary? Vitamin C, alone or with other nutrients, could be a real revolution in the coming decades. The revolution that millions of sick people and their families are waiting for in silence. Since the body eliminates the vitamin C that it does not need every four or five hours through the urine, one way to keep the level stable is to consume some food rich in vitamin C distributed throughout the day.

The studies of Padayatty in 2004 with the oral and intravenous forms and of Hickey in 2008 with the liposomal form open a field for new studies.

Without taking it as a general recommendation and bearing in mind that the doctor must be the one who adjusts it to each patient (state of health, other diseases and medications, previous renal problems, etc.), Padayatty's study in 2004 reached revolutionary conclusions: by oral means a blood concentration three times greater than that supposed possible before could be achieved. Three grams every four hours led to 220 micromoles per litre (previously it was believed that it was only possible to reach 80 micromoles per litre orally).

Vitamin C, both from food sources with lemon juice with water (Yazawa 1994) and from supplements, improves the benefits of levodopa and reduces adverse effects (Sacks 1975).

For the treatment of motor fluctuations soluble levodopa has been proposed: e.g. 10 tablets of Sinemet-Plus in 1 litre of water with 1 gram of vitamin C, take 100 ml every 90 minutes (Kulisevsky 2013). Always with the guidance of a neurologist.

Vitamin C, alone or with other nutrients, could be a real revolution in the coming decades. The revolution that millions of sick people and their families are waiting for in silence.

Given that the body eliminates the vitamin C that it does not need every four or five hours through the urine, one possibility of keeping the level stable is to consume some food rich in vitamin C distributed throughout the day.

Changes in Science and Medicine go slowly, too slowly for the sick and their families. Perhaps we should help doctors and researchers, bringing the experience and experiences of patients to accelerate these changes.

If it does not harm the patient and the neurologist does not advise against it, why not try it?



5. Vitamin C at the frontier of what we know about "Parkinson's diseases".


The oxidative hypothesis of Parkinson's disease.


Dr. Sir William Osler ("father" of Modern Medicine) believed that Parkinson's was caused by accelerated aging of the brain. In the original, "state of accelerated aging" (The Principles and Practice of Medicine, 1892. -in Rajesh Pahwa, Kelly E. Lyons. Handbook of Parkinson's Disease, p. 14-).

The prestigious neurologist Warren Olanow reported on the role of free radicals and metabolites (remnants) of levodopa therapy in neuronal death. This hypothesis suggests that antioxidant therapies may slow the rate of progression of PD and shows concern that metabolites -rests- from levodopa treatment may accelerate the rate of neuronal degeneration (Olanow 1990).

Jenner and Olanow showed the role of oxidative stress in the pathogenesis (origin and evolution) of Parkinson's disease, especially iron content in the brain, damage to mitochondria, lack of antioxidant protection, superoxide dismutase (SOD) and reduced or active glutathione (GSH) (Jenner and Olanow 1996).

Will vitamin C be oxidized -because it crosses the protective barrier of the brain and the membranes of neurons and mitochondria- and active glutathione -because it devotes its antioxidant capacity once inside it- keys to the cause and progression of Parkinson's?

We insit on something that could be of paramount importance. Vitamin C cannot cross the barrier that protects the brain. It oxidizes and can (as dehydroascorbic acid). And once in the brain it is activated again (redox mechanism) thanks to glutathione. Thus it is able to reduce the damage caused by the oxidation of the remains of levodopa in the substantia nigra and other areas of the brain (Pardo 1993, Berg 2001, Riederer 1989, Florence 1988, Offen 1996). It also occurs with neurons and mitochondrias.

Parkinson's patients have a low glutathione level, which also affects the mechanism of reduction of the oxidized form of vitamin C. This could leave the substantia nigra and mitochondria defenceless, by a very low or insufficient level of GSH (reduced glutathione) and of ascorbic acid/dehydroascorbic acid for the increased needs in Parkinson's patients and more when they are treated with levodopa.

We know that the possible neuroprotective effect of the drug selegiline is due to the fact that it slightly elevates glutathione (Tanaka 2002). Why not try in future studies administering better liposomal glutathione, NAC, etc.?

Studies with NAC (N-acetylcysteine) have shown that it multiplies by almost three - 3.4% to 8.3% - the dopamine transporters (DAT), which makes the scarce dopamine produced by the brain of patients in advanced stages is better used and more effective (Monti 2019).


Is a multicarential hypothesis reasonable?


Is Parkinson's disease a set of multiple deficiencies? Why do so many vitamins and minerals prevent or reduce the risk of the disease?

As early as the 1970s, vitamin deficiencies in Parkison patients were mentioned. Among others, vitamin E, vitamin B12 and folic acid with high levels of homocysteine, riboflavin, vitamin D, vitamin K, glutathione, magnesium, vitamin C and vitamin B6 (Cawein 1970).

Dr. Marty Hinz completed the list of multiple deficiencies in patients before and after starting treatment (Hinz 2011, 2016), which had already been mentioned in part by other researchers (Karobath 1971; Charlton 1992, 1997).

Dopamine deficiencies occur in patients, but also in many other things, such as tyrosine hydroxylase, norepinephrine and serotonin (Charlton 1992, 1997; Karobath 1971). Those taking levodopa also reduce tryptophan, sulphur amino acids such as glutathione and SAMe, epinephrine (Karobath 1971, Zhelyaskov 1968, Hinz 2010, Liu 2000, Fuller 1982)...

Other researchers had already pointed, before Hinz, towards glutathione deficit -Sechi in 1996-, magnesium deficit -Barbiroli in 1999-, or high homocysteine level -Yasui in 2000 and Muller in 2001-, as responsible for the severity of the symptoms and the current progression of the disease.


Is there parkinsonism for scurvy?


There is Parkinsonism caused by severe deficiency of vitamin C or scurvy (Nobile 2013; Quiroga 2014). It is not strange since ascorbic acid is antioxidant and anti-inflammatory, regulates cortisol (the stress hormone), converts dopamine into norepinephrine, tyrosine into dopa, synthesizes carnitine, activates vitamin B9 which regulates the neurotoxic homocysteine, regulates the glutathione level and a thousand other things.



6. Some final reflections.

We are close to very important changes in the Parkinson's world. Given the forecasts made by experts such as Dorsey, it is no longer a question of whether there will be but when they will be made. Prevention by promoting the use of polyphenols from green tea or vitamins C and E in foods (as is done by fortifying foods with vitamins such as B1 and B3). And it may be necessary to use the media (successful programmes, television series, films, etc.). As well as oral, liposomal and intravenous vitamin C studies, similar to what the famous neurologist Stanley Fahn did in 1992 with vitamins C and E.

It does not seem crazy to say that the future of the Parkinson's world, to find a way out in the current parkinsonian labyrinth, depends very much on the acceptance of vitamins, minerals and other nutrients in the treatment of the disease. And we will see in the next decade. It will mean a real revolution. And vitamin C will play a very important role in that future world without Parkinson's that I dream of.

I am convinced that the basis for the cure of this disease is already in the published studies and especially in those that have appeared in the last two or three years. We only have to find figures of social and scientific prestige that give the necessary impetus to initiate changes: perhaps a large-scale prevention and the development of new protocols before and after starting with levodopa - which correspond to researchers and doctors establish - but I suspect they'll be a lot like the protocol Dr. Marty Hinz has proposed.

If we don't do this or something else, future generations will judge us extremely harshly.



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WARNING. Any change should always be consulted with the doctor and the pharmacist, who can assess many aspects that escape the knowledge and experience of the patients and their families.

Courage is good medicine. But prudence too.



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LIST OF STUDIES MENTIONED IN THIS ARTICLE (its purpose is not to adorn the article or appear a scholarship that corresponds to the wise consulted, but to show that there is "much Science and Medicine" supporting the proper use of vitamin C):

Acuña, Reiter (1997). Melatonin is protective against MPTP-induced striatal and hippocampal lesions. Life Sci.

Ahulé (2019). Dehydroascorbic acid S-Thiolation of peptides and proteins: Role of homocysteine and glutathione. Free Radic Biol Med.

Berg (2001). Brain iron pathways and their relevance to Parkinson's disease. J Neurochem.

Bruno (2006). Faster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation. Free Radic Biol Med.

Callus (2018). Scurvy is back. Nutrition and Metabolic Insights.

Cantatore (1991). The importance of vitamin C for hydroxylation of vitamin D3 to 1,25(OH)2D3 in man. Clin Rheumatol.

Cawein (1970). Vitamin preparations for patients with Parkinsonism. N Engl J Med.

Cerhan (1994). Antioxidant intake and risk of Parkinson´s Disease in older women. Am J Epidemiol.

Charlton (1992). Parkinson's disease-like effects of S-adenosyl-L-methionine: effects of L-dopa. Pharmacol Biochem Behav.

Charlton 1997). Depletion of nigrostriatal and forebrain tyrosine hydroxylase by S-adenosylmethionine: a model that may explain the occurrence of depression in Parkinson's disease. Life Sci.

Crook (1941). The system dehydroascorbic acid-glutathione. Biochem J.

De Rijk (1997). Dietary antioxidants and Parkinson´s Disease. The Rotterdam Study. Arch Neurology.

Delangue (2007). Vitamin C deficiency and scurvy are not only a dietary problem but are codetermined by the haptoglobin polymorphism. Clinical Chemistry.

Deverenkov (2018). Studies on the Reduction of Dehydroascorbic Acid by Glutathione in the Presence of Aquahydroxocobinamide. European Journal of Inorganic Chemistry.

Dorsey (2007). Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology.

Dorsey (2018). The Emerging Evidence of the Parkinson Pandemic. J Parkinsons Dis.

Englard (1986). The biochemical functions of ascorbic acid. Ann Rev Nutr.

Fahn (1992). A pilot trial of high-dose alpha-tocopherol and ascorbate in early Parkinson's disease. Ann Neurol.

Florence (1988). Neurotoxicity of manganese. Lancet.

Gan (2008). Vitamin C deficiency in a university teaching hospital. J Am Coll Nutr.

Gao (2012). Habitual intake of dietary flavonoids and risk of Parkinson disease. Neurology.

Guz (2017). The role of vitamin C in epigenetic regulation. Postepy Hig Med Dosw.

Halpner (1998). Protection by vitamin C of oxidant-induced loss of vitamin E in rat hepatocytes. J Nutr Biochem.

Hellenbrand (1996). Diet and Parkinson's disease. II: A possible role for the past intake of specific nutrients. Results from a self-administered food-frequency questionnaire in a case-control study. Neurology.

Hinz (2011). Amino acid management of Parkinson’s disease: a case study. Int J Gen Med.

Hinz (2016). Parkinson's disease managing reversible neurodegeneration. Neuropsychiatr Dis Treat.

Jacob (1995). The integrated antioxidant system. Nutr Res.

Jacob (1997). Urinary carnitine excretion increases during experimental vitamin C depletion of healthy men. J Nutr Biochem.

Karobath (1971). The effect of L-dopa on the concentrations of tryptophan, tyrosine and serotonin in rat brain. Eur J Pharmacol.

Katsuki (1996). Vitamin C and nervous tissue. In vivo and in vitro aspects. Subcell Biochem.

Krajcovicova-Kudlackova (2002). Homocysteine and vitamin C. Bratisl Lek Listy.

LeBlanc (2013). Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr Opin Biotechnol.

Linazasoro (1995). Treatment of complicated Parkinson disease with a solution of levodopa-carbidopa and ascorbic acid. Neurologia.

Maher (2002). Epidemiologic study of 203 sibling pairs with Parkinson's disease: the GenePD study. Neurology.

Noble (2013). Old disease, new look? A first report of parkinsonism due to scurvy, and of refeeding-induced worsening of scurvy. Psychosomatics.

Offen (1996). Prevention of dopamine-induced cell death by thiol antioxidants: posible implications for treatment of Parkinson´s disease. Exp. Neurol.

Oyarce (2014). The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism. Journal of Neurochemistry.

Pardo (1993). Ascorbic acid protects against levodopa-induced neurotoxicity on a catecholamine-rich human neuroblastoma cell line. Mov Disord.

Postuma (2006). Vitamins and entacapone in levodopa-induced hyperhomocysteinemia: a randomized controlled study. Neurology.

Quiroga (2014). Ascorbate and zinc responsive parkinsonism. Ann Pharmacother.

Rabin (1989). Bidirectional interaction between the central nervous system and the immune system.Crit Rev Immunol.

Raynaud-Simon (2010). Scurvy in hospitalized elderly patients. J. Nutr. Health Aging.

Reutens (2002). Homocysteine in neuropsychiatric disorders of the elderly. Int J Geriatr Psychiatry.

Riederer (1989). Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J Neurochem.

Rebouche (1995). Renal handling of carnitine in experimental vitamin C deficiency. Metabolism.

Sacks (1975). Ascorbic acid in levodopa therapy. Lancet.

Seitz (1998). Ascorbic acid stimulates DOPA synthesis and tyrosine hydroxylase gene expression in the human neuroblastoma cell line SK-N-SH. Neurosci Lett.

Singh (1995). Dietary intake and plasma levels of antioxidant vitamins in health and disease: a hospital-based case-control study. J Nutr Environ Med.

Smith (2011). Scurvy in the developed world. Can. Med. Assoc. J.

Yapa (1992). Detection of subclinical ascorbate deficiency in early Parkinson's disease. Public Health.

Young (2015). Regulation of the Epigenome by Vitamin C. Annu Rev Nutr.

Zisapel (2001). Melatonin-dopamine interactions: from basic neurochemistry to a clinical setting. Cell Mol Neurobiol.

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