Vitamin C in the world of Parkinson´s

[parkinsonshereandnow]

"Once you eliminate the impossible, whatever

remains, no matter how improbable, must be the truth."

Arthur Conan Doyle, "Sherlock Holmes."

Introduction.

Could vitamin C be an essential element in 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 NATURAL DOPA 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 (tryptophan is also a precursor of the famous melatonin).

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.

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%.

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. 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 neurologists like Jenner and 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 1992).

They 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 truly 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.

-----

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.

I apologize for the errors in the use of the English language. My first language is Spanish. I would appreciate any correction. Thanks.

------

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.

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.

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.

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.

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.

---

Jesus Marquez Rivera. Parkinsons here and now. 12/03/2019

[park_bear]

I had to look up multicarential which apparently refers to multiple nutritional deficiencies.

It is clear that insufficient vitamin C causes multiple problems. That said, in my experience, high-dose vitamin C does not make any difference to my Parkinson's except for relieving constipation.

[CaseyInsights]

Don’t want to sound as a broken record but this subject was raised just two months ago. The discussion paper - Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders?

Discussion and paper here -

healthunlocked.com/parkinso...

And do be careful with references to Marty Hinz. He had one of his major papers retracted.

See here -

ncbi.nlm.nih.gov/pmc/articl...

HU Discussion here (three years ago, before the retraction)

healthunlocked.com/parkinso....

Search the site - the information you present is all here. Again why are people still struggling if they have access to information you think revolutionary?

Put together a comprehensive explanation of the disease and its progress, construct a matching framework that identifies the key drivers and match nutraceuticals to these drivers and you will have an eager audience

✨🏋🏽‍♀️✨

[Viking6 in reply to CaseyInsights]

Vitamin C may have several positive effects on Parkinson, but perhaps it should be used with caution since that vitamin can increase the absorbtion of iron, and as far as I understand, high iron may cause problems for persons with Parkinson's disease. It may be better not to take vitamin C in combination with iron rich foods.

youtu.be/RpMEMX-c7VU(Not working as expected?)

[JayPwP in reply to Viking6]

See related discussion here

healthunlocked.com/parkinso...

[parkinsonshereandnow in reply to CaseyInsights]

I don't understand the point of your comment. Maybe it's because I still don't quite grasp the nuances of English.

1) The discussion paper (Kocot 2017) deals with several aspects that are included in my text, which is a summary for dissemination, not a work that aims to "exhaust the subject".

Unlike you, I see no opposition between the excellent comments by rescuema and others and my summary in a kind of FAQ, the original of which I wrote 4-5 years ago. Or with Kocot's excellent 2017 study.

I always work on what many others have already published and learn from what they know. And of course, I quote whenever I can.

My job is to search and retrieve in order to disseminate, and to bring to many people what is the privilege of the few. I don't know what the situation is like in the English-speaking world, but in the Spanish-speaking world not even 1% know that vitamin C is important for Parkinson's disease.

2) The fact that Hinz's work was retracted not only does not detract from its interest for me, but increases it. Debating what medical journals stand for, the pressures they are under, has been publicly confessed by former editors of Lancet, New England Journal of Medicine, Nature, etc., but I don't think it is of much benefit to sufferers looking for hope and solutions.

I am interested in what Hinz says, not where he says it or the opposition it generates. Especially about the multiple deficiencies (already said years ago by Karobath and Charlton, among others; or about the adverse effects of levodopa and carbidopa). Surely less than Linus Pauling, who was right about the role of vitamin C in colds and cancer, as studies in recent years are showing (Hemila 2017, Ran 2018; and Chen 2005, 2008; Ma 2014; Hoffer 2015, respectively).

3) People are still struggling because the information available to them is incomplete. It is not enough to take vitamin C. Even the 3 grams a day that Fahn used in 1992 may be too little.

Dosage is the key: with coenzyme Q10 (Shults 2002); with vitamin B2 (Coimbra 2002); with vitamin B1 (Smithline 2012, Costantini 2013, 2015); with vitamin D (Hiller 2018, Fulda 2020); with B12 (Christine 2018, McCarter 2020), with melatonin (Reiter, Pierpaoli, Acuña...), etc.

As Cotzias and Fahn recount, in the 1960s levodopa itself was rejected until it was given in very high doses. And so it caused such adverse effects (nausea and vomiting) that it needed further changes to be viable (Cotzias' studies in 1967, Sin-emet).

Some things I have been able to contribute. I would not dare to say revolutionary, but they do seem important to me: bringing to the stage the Smithline study of 2012, in which he says that high doses of B1 had already been used safely for other diseases (that generates confidence in the sick and relatives who do not decide to trust what they say about B1), or the Fulda study of 2020 in which he acknowledges that doses of 10. 000 IU of D3 had already been used in other diseases without the slightest problem of those that are usually adduced to fear such doses (which does not go against the need for medical supervision) and that it is what the body synthesizes in 30 minutes of sun in summer...

---

A profound change is needed in medicine and neurology, as stated by prestigious scientists and neurologists (some writings by Birkmayer, by Oliver Sacks himself, by Professor Dorsey...).

Coimbra, Permutter and many other neurologists have already taken steps forward. But the obstacles are many. And I am not going to talk about the "elephant in the room"....

If I can bring something "new" to the world of Parkinson's, this is the way... to search and search again, to collect and re-expose in the simplest and most impactful way I can. And learn as much as I am doing in this wonderful forum.

[CaseyInsights in reply to parkinsonshereandnow]

...maybe you are right: what you have found needs to be repeated ad nauseam until understanding dawns.

But I was just hoping, given the wealth of your understanding, that you go beyond regurgitation of what you have found, to a synthesis that carries us further, illuminating a clear path forward. Maybe that will come at some later date.

And your English is fine 🌺

[Despe in reply to CaseyInsights]

Your reply to "parkinsonshereandnow" is rude and unacceptable. He put a lot of work into it. I understand we have read and posted in this forum covering vitamins/supplements/minerals, over and over, however, I would thank him for his efforts. You remind me of all the new members who ask questions about subjects that we have discussed countless times. Would it be right to answer to them the way you did to "parkinsonshereandnow"?

[CaseyInsights in reply to Despe]

...and you have made yourself the arbiter of what is acceptable and not acceptable on HU 😢

[parkinsonshereandnow]

In 2019 I finished and published on Amazon a book about vitamin C (only in Spanish). Unfortunately I don't have time or money to make an acceptable translation of the whole text. But I think that this fourth chapter may help some sick people, always with the approval of the specialist. I think the keys are the dosage and the way to take it. This is not a summary for better dissemination. This may be new to some PwP.

Chapter 4.

Forms or routes of administration.

"The most beautiful thing we can experience

is mystery. It is the fundamental emotion

that supports true art and true science".

Albert Einstein

We are increasingly aware of the oral forms of vitamin C, which, whether from food or supplements, are a mainstay of health, prevention and possible cure for many diseases. The intravenous (drop-by-drop, parenteral) form has seen an increase in its use in alternative clinics around the world (beauty therapies, regeneration, anti-cancer, etc.) and in the number of scientific studies, which are becoming more and more precise and rigorous (Chen 2005, 2008; Ma 2014; Hoffer 2015...).

Liposomal vitamin C is a special case. Although it is taken orally, the fact that it is "encapsulated" in healthy fat microspheres and ensures an assimilation rate of close to 90% makes it different from the others. Very powerful and effective. Few predictions are made in this book. One of them is that when the liposomal, traditional oral and intravenous forms are used together in studies on cancer, Parkinson's, Alzheimer's, etc., the results may be astonishing. And even more so if they are enhanced with other nutrients, such as alpha-lipoic acid, zinc or bioflavonoids.

Forms of administration. Oral. Oral liposomal. Intravenous. Nasal. Topical.

Vitamin C is consumed orally in most cases. Both the dietary and the main form of supplementation. It can also be taken nasally, topically, intramuscularly, intravenously... depending on the health problem to be treated.

The most common forms are oral (capsules, tablets, effervescent tablets, delayed release, etc.) and intravenous (intravenous or parenteral, drop by drop like the IV bag used in clinics and hospitals).

Nasal is used for upper respiratory problems (rhinitis, allergies, etc.) and topical (cream) for beauty and dermatological treatments.

Intramuscular was used by the journalist Norman Cousins who asked his doctor Dr. Hitzig for it. But when higher doses were needed, the intravenous route was used.

ORAL.

Industrially produced ascorbic acid is available in a wide variety of supplements: tablets, capsules, chewable tablets, crystalline powder, effervescent tablets and liquid form.

We already know that both natural and industrially synthesised ascorbic acid are chemically identical and there are no known differences in their biological activities or bioavailability (Yung 1982).

The liposomal form is, in some respects, a different form of administration (Yung 1982).

Although consumed orally, vitamin C bypasses the digestive system thanks to the fat microspheres.

Since 2004, Padayatty and colleagues have found that only 220 micromoles/L could be achieved orally using high doses spread throughout the day, whereas previously it was thought that only 70-80 micromoles/L could be achieved (Padayatty 2004). This concentration does not appear to be sufficient to achieve the selective cytotoxicity needed to kill cancer cells in vitro and also in vivo.

ORAL LIPOSOMAL.

Liposomes were first proposed as a drug delivery system in the 1990s (Bangham, 1995; Gregoriadis, 1995). Dr. Alec Banham, a haematologist at the Babraham Institute in Cambridge, UK, created the liposomal technology. The main reason for using liposome encapsulation is to ensure almost complete absorption of the nutrient or drug. The liposome eliminates the need for digestive activity prior to absorption. There are dozens of drugs that use this technology.

In addition, it appears that the increased absorption along with the phospholipid dosage at the same time has health benefits.

The liposomal form can be considered as a form of delivery, as it is mainly ascorbic acid within fat or phospholipid microspheres (non-GMO sunflower or soy lecithin). It is a double layer of fatty materials that is similar to the phospholipid double layer of the body's cell membranes.

Liposomal vitamin C can achieve 10-15 times the bioavailability, thus providing many more benefits. Absorption of the oral forms when administered in a 1000 mg amount is generally 1000 mg is usually 50-150 mg; 1000 mg by infusion is usually 600-700 mg; in the case of liposomal oral, 1000 mg achieves 900-950 mg assimilation (Davis 2016).

Some experts in the field of vitamin C, such as Dr Thomas Levy, say that 6 grams of liposomal vitamin C are equivalent to 50 grams of intravenous vitamin C. In other words, it is similar to intravenous vitamin C therapy, but without the cost, personnel and time required to administer it. And without the fear of the needle. It is a costly but effective procedure that is quite often performed in hospitals and health clinics as alternative therapies.

Drs. Thomas Levy (cardiologist and world authority on vitamin C) and Joseph Mercola (osteopathic physician and author of one of the leading natural health websites in the USA) are strong advocates of this form of vitamin C administration.

It has a much higher absorption rate than traditional oral vitamin C, at over 90%. This is even far superior to intravenous vitamin C.

The correct size is between 100 and 400 nanometres. They must be tested in a facility regulated by the authorities to ensure their safety and quality.

It seems that after Padayatty's 2004 study of blood concentrations of 220 micromoles/L (3 times more than what was thought possible orally), Hickey and Roberts' 2008 study has opened up a very promising future for research into the concentrations that can be achieved with liposomal vitamin.

According to Hickey and Roberts, a single 36-gram dose of liposomal vitamin C can raise the level to over 417 μM/L (Hickey 2008).

In an in vitro study, the use of ascorbate to treat Burkitt's lymphoma cells by producing H2O2 or hydrogen peroxide, in 54

concentrations of 300 μM/L showed 30% necrosis and apoptosis. When increased to 400 μM/L, tumour cell death rose to 50 % (Chen 2005).

The Hickey and Roberts study mentions the research of two physicians:

Dr Hunninghake (2008) administered 10 grams of normal vitamin C followed by 12 or 18 grams of liposomal, divided at intervals throughout the day, maintaining a level around 300 μmol/L.

Dr Bolhuis (2008), using combinations of normal and liposomal vitamin C (24.4 g normal and 8 liposomal), went as high as 512-579 μmol/L.

Hickey and Roberts predicted that plasma vitamin C levels of 500-600 uM/L could be achieved orally with repeated liposomal doses throughout the day (in their article "The new potential of vitamin C").

This research opens up avenues of hope for certain diseases, but it is experimental and should not be implemented without the approval of a sufficiently experienced specialist. The same precautions may be necessary as for intravenous administration of megadoses, in particular for kidney and iron problems.

INTRAVENOUS.

Pioneering physicians such as Klenner, Cameron, Cathcart, Riordan, used high doses intravenously to treat all kinds of diseases. This parenteral route uses bags similar to the usual IV bags and the administration takes place slowly, drop by drop.

Because it does not pass through the digestive system, intravenous administration 55

Because it does not pass through the digestive system, intravenous administration increases blood levels tens or hundreds of times more than when administered orally (Padatatty 2004). Only by the oral route does the natural mechanism work to limit the amount of vitamin C that is assimilated and the elimination of the remainder in the urine and faeces (kidneys and intestine).

As early as the 1930s, Marin (1936) treated a patient with scurvy who did not respond to the anti-scorbutic diet and had to add intravenous ascorbic acid to cure him. An infection caused bacteria to destroy the vitamin C in the amount he was able to receive from the diet (Marin 1936).

Riordan's intravenous vitamin C protocol involves the slow infusion of vitamin C in doses on the order of 0.1 to 1.0 grams of ascorbate per kilogram of body mass (Riordan 2003).

The use of the intravenous route has recently increased among practitioners of integrative and orthomolecular medicine: a survey of approximately 300 practitioners between 2006 and 2008 reported that approximately ten thousand patients received it, at an average dose of 0.5 g/kg, with no significant adverse effects (Padayatty 2010).

Although intravenous vitamin C may have a variety of possible applications, such as fighting infections (Padayatty 2010), treating rheumatoid arthritis (Mikirova 2012), it has generated the most interest for its use in cancer treatment, alone or accompanying chemotherapy and radiotherapy to reduce its adverse effects and/or improve its efficacy (Mikirova 2009; Hoffer 2015; Klimant 2018; Carr 2018).

Cancer studies continue to be published with increasingly important results.

In 2004, Padayatty and colleagues found that very high blood concentrations were only possible using the intravenous route (Padayatty 2004).

Alan Smith and his recovery from bird flu.

Alan Smith's case study (2009) shows the powerful effect of intravenous and liposomal vitamin C..., whether anecdotal or generalisable. If confirmed, as has happened with Marik's protocol for the terrible sepsis, based on thiamine, hydrocortisone and sodium ascorbate, it would be of tremendous benefit to mankind.

New Zealand cattle farmer Alan Smith made a miraculous recovery from a coma caused by severe pneumonia and leukaemia. After a holiday in Fiji, he contracted bird flu. His condition was so serious that doctors were ready to pull the plug when the family begged them to try high-dose intravenous vitamin C. After strong resistance in the absence of studies, he began to show a positive response after the doctors gave him 50 grams of intravenous vitamin C. The doctors were probably concerned about his condition.

The doctors at the hospital were probably concerned about any possible complications with the high dose of intravenous vitamin C. They reduced it to 2 g and Alan was able to take it again. They reduced it to 2 g and Alan Smith started to get worse again. His family gave him 6 grams of oral liposomal vitamin C and within a few weeks he felt much better and was discharged from hospital.

Today he lives a normal life and lectures about his case.

NASAL.

The nasal route is referred to in forums on vitamin C to deal with allergies, rhinitis, etc., so caution should be exercised and good information should be provided. It is usually prepared with sodium ascorbate and water. The key is to avoid irritation of the nasal mucosa, so ascorbic acid is not used.

It is administered by spray, drops or by wetting a cotton swab. Some commercial nasal sprays with sodium ascorbate have already appeared.

Linus Pauling claimed that this form of administration increased the concentration in the nasal area 1000-fold, citing Braenden (1973).

TOPICAL (SKIN).

Vitamin C is very successful in the world of cosmetics. Masks, creams to protect the skin, etc.

Advertising refers to its capacity to produce collagen, elastin, etc., and protect the skin from the sun, the air or the signs of ageing.

Magnesium ascorbyl phosphate is a compound formulated from ascorbic acid that is considered an effective antioxidant for the skin. This form of vitamin C also increases skin hydration levels and improves skin elasticity.

It appears effective in inhibiting melanin production and lightening the skin. It is used in lotions, sun creams, after-sun products and make-up.

[chartist]

Jesus,

Your command of the English language sounds better than mine! I do not ever remember hearing the word multicarential in my life and I certainly did not know what it means.

Something that really bothers me is that many supplements suggest promise in improving the state of PD, but the needed studies are clearly lacking in quantity, quality and dosing. The conclusion I have come to is that there is insufficient incentive, as in money, to actually get those needed studies that suggest the potential to be life changing for PwP.

The end result is that PwP as well as people with other diseases are left to have to rely on the minimal good studies in combination with anecdotal evidence by PwP who are willing to test these supplements on their own which makes for very slow going with minimal progress.

This forum is such a place where some members have taken it upon themselves to test supplements on their own and then generously share their results with other members. To me that makes this forum somewhat unique when compared to other forums and in the sense of supplements, fairly progressive. Obviously the pharmaceutical industry is not going to do the needed testing as they can't make any money off of supplements which they can't patent.

That leaves universities and institutions such as the NIH as the main places to perform these studies and as most can see, that is a very slow means of getting new information of value. You would think that a foundation such as MJFF would have funded or at least contributed monetarily to the funding of B1, but they said no! Another reality is that many studies that had good potential to show very positive results, used dosing that was way too low to achieve the best results and even when they get decent results at relatively lower dosing, there are no follow up studies at higher dosing that has already proven to be safe in other disease states.

Even in the world of prescription medicine, C/L came available around 1970 and has now been the gold standard treatment for PwP for over 50 years now! I don't know what the answer is, but I think this forum is helpful for the members who share the information they are able to get with other members.

To me, all of this is a bit frustrating! I do appreciate the research you have put into what you write and the effort that you put into it on behalf of others!

Art

[parkinsonshereandnow in reply to chartist]

Hello, Art.

Thanks for your words.

I'm afraid I've perpetrated a new Spanglish word: "multi-carential" following in the wake of "multifactorial". From now on I will use multiple deficiencies (and leave "multi-carential" in quotation marks) or multiple deficiency syndrome.

I start with a certain advantage when it comes to supplements: years ago I developed allergic asthma. Every flare-up was hell, despite tons of medication and corticosteroids. According to my pneumologist it would be forever.

I don't remember how, I started taking half a gram of vitamin C, then 1, 2, 5, 10 and the symptoms disappeared. I was very scared but I did it. Something told me to keep going. Intuition? The official sites said it was a waste of money.

After a year, my doctor told me I didn't need medicine. I haven't taken any for 15 years. Thanks to magnesium, zinc or vitamin D3, I can reduce the daily dose of vitamin C.

After some time, I found studies on the anti-allergic power of vitamin C in relation to the dose, proportional to the level of histamine in the blood - I believe that one molecule of ascorbic acid neutralises each molecule of histamine (Chatterjee 1978).

And as for every vitamin or mineral, the studies are contradictory, inconclusive and all a series of "mantras" that are repeated over and over again. So I decided to stick with the positive ones when they are solid and the authors are prestigious.

So far, my overall view is that we know quite a lot about the disease and its possible treatments, but the problem lies in the "Parkinson's world". A giant of colossal proportions that would die if a cure or an effective treatment for Parkinson's were announced tomorrow. And the "elephant in the room": BigPharma.

I am writing a new book in English and Spanish. And it is addressed to each patient according to the stage he or she is in. Not to expose "everything" that is known, but at least so that they don't start from scratch or lost in the official jungle or in the alternative.

I have found "HealthUnlocked" 27 years after I started my relationship with Parkinson's. This is unacceptable. We need sites and books that serve as a guide for all sufferers.

I would love to be able to interview Professor Dorsey. And then chat with him privately for an hour. It is intolerable that from 1990 to 2015, we have twice as many Parkinson's sufferers in the world. And there are no preventive campaigns like the 1940's pellagra campaign in the USA by fortifying flour with vitamin B3. We are living something with the characteristics of a Parkinson's "pandemic" (wars against tobacco and cholesterol? powerful neuroprotectors; a society of stress and low magnesium, thousands of chemicals, etc.).

Unfortunately I have very little free time. Now I take care of my mother. If she continues to improve, I will have more time in a few months. All attempts to find a publisher, a patron, etc., have failed. I'd have to sift through Medline, review PIENO, peruse HealthUnlocked, etc.

I remember my father asking me a few weeks before he died not to leave the Parkinson's patients "alone". I think he came to understand the world of Parkinson's better than he confessed to me.