It is not frequent that possible clusters are located or declarations of affected persons are made when a subclinical deficiency would be difficult to detect by current Medicine and much less by the person who suffers it. The lack of vitamins is not strange, although it is often ignored by both doctors and patients. This is usually the case with vitamins B12 and D, as well as B9 (or its consequence in high levels of the very toxic homocysteine).

Studies are not many, but fortunately there are:

1. - Several studies with Parkinson's patients have shown that vitamin C deficiency is associated with idiopathic Parkinson's and some form of parkinsonism (Yapa 1992, Quiroga 2014, Medeiros 2016, Hughes 2016). Even when measured in lymphocytes rather than plasma, a significant reduction in vitamin C has been seen in relation to increased severity of symptoms (Ide 2015).

2. - A diet rich in vitamin C has been associated with a lower risk of developing Parkinson's, while a poor diet has been associated with an increased risk (Cerhan 1994, Singh 1995, De Rijk 1997). Despite numerous studies of opposite outcomes, Hellenbrand and colleagues found a risk reduction of about 40% (Hellenbrand 1996): "We found an inverse association between the intakes of beta-carotene (OR = 0.67, 95% CI: 0.37-1.19, p trend = 0.06) and ascorbic acid (OR = 0.60, 95% CI: 0.33-1.09, p trend = 0.04) by patients, although only the trend for ascorbic acid intake reached statistical significance. "
I found the first three studies on the value of nutrition from a book that is one of my treasures: "Textbook of Nutritional Medicine." by Dr. Melvyn Werbach.

3. - Delays the need for medication by 2.5 years (Fahn 1992). Since the DATATOP study denies benefits in this sense to a part of the vitamin E (alpha-tocopherol), we can deduce that the effect is produced by the 3 grams daily during 1 year used by the famous American neurologist Stanley Fahn and that unfortunately he did not continue the trials with higher doses or combined with the liposomal form (which started to be tested in the 90's for fully orthodox medicines or in intravenous or parenteral form - used in numerous studies of the 70's and 80's).

4. - Vitamin C is a highly effective antioxidant and is particularly adept against hydroxyl radicals (the main culprits in the dopamine-cell destruction), it is becoming increasingly clear that this vitamin may be an excellent protector against Parkinson's disease and can materially help in slowing down the progression of the disease (Przedborski 1995).


Hellenbrand, Fahn and Przedborski are renowned neurologists and researchers. The years of their studies are interesting: 1992, 1995 and 1996. As well as those related to diet: 1994, 1995 or 1997. As a historian, it strikes me that after 1997 they did not continue to confirm such encouraging results. Another of the "paradoxes" of the Parkinson's world (such as the neglect of the treatment of high homocysteine in most patients treated with levodopa or the maximum dose of vitamin B6 up to 25 mg allowed by the levodopa prospectus since 1975 thanks to the use of carbidopa or benserazide, so that their drug can be converted into dopamine).

The studies of Yapa in 1992 and Ide in 2015 seem to me to be the most promising for the near future. The first by detecting subclinical deficiency at the beginning of the disease and the second by detecting a strong deficiency in the lymphocytes as the symptoms became more severe (as with magnesium (Barbiroli 1999), glutathione (Perry 1982, Riederer 1989, Sechi 1996, Jenner 1998), with the level of neurotoxic homocysteine (Yasui 2000, Muller 2001, Christine 2018, Saadat 2018) and with B12 (Leigh 2018, Christine 2018, McCarter 2019), while the decrease of vitamin C in plasma is not so evident. We have not known this peculiarity of vitamin C until 2015, so it is very likely that there are others. For example, in 2004 Polidori and Padayatti, in different studies, found that the maximum level in the blood by mouth was 240 micromoles per liter, when until then it was believed that only 80 could be reached.

I think Yapa's conclusion in his study is important: "This indicates a significantly higher prevalence of Parkinson's disease in the group with Vitamin C deficiency (P less than 0.001 using Fisher's exact)."

Vitamin C increases the production of dopa (by hydroxylation of tyrosine) and improves the absorption of levodopa in older patients or those with absorption difficulties (Seitz 1998, Nagayama 2004, Zhao 2019).

There is a strong relationship between vitamin C and Parkinson's, both in the risk of developing Parkinson's and in the early and advanced stages. And to improve assimilation and avoid damage to the main drug so far: levodopa.
First of all because it is theoretically evident (even if the necessary studies did not yet exist).
Second, because there are, despite the difficulty of applying to nutrients studies that have been designed for allopathic medicines, as some experts have already proposed. The measurement in lymphocytes rather than in plasma (Ide 2015),
And finally, because it is a central element in the whole edifice of human neuroprotection: glutathione is dependent on vitamin C, the activation of folate that regulates the lethal homocysteine, is essential in the synthesis of dopa (from tyrosine) and norepinephrine (from the low dopamine), and in the protection of the mitochondria in the oxidized form that crosses the protective barrier of the brain and enters the mitochondria - the main focus of oxidation -, in the double hydroxylation of vitamin D in the liver in the kidneys, in the "redox" mechanism that allows the recovery of vitamin E and flavonoids, etc.

If there are not many studies, it is not the "fault" of vitamin C. There is also a lack of willingness to do certain studies, partly because of the difficulty of designing them correctly for vitamin C. I will give several examples of what I mean by three cases: penicillin, levodopa itself and saturated fats as responsible for increased cardiovascular risk.

1) Already Alexander Fleming was on the verge of throwing in the towel in the 1930s because all the studies gave negative results regarding the capacity of penicillin as an antibiotic in humans. Other scientists and new types of studies had to come along in the 1940s to find its true value, in the context of World War II.

2) Oleg Hornikiewicz himself came close to giving up on levodopa in the 1960s until Cotzias arrived with his 1967 studies (as reported by Fahn in 2015). The amount of levodopa needed to achieve benefits was so high that the adverse effects were intolerable. The use of L-dopa and dopa decarboxylase inhibitors greatly improved the situation, but not entirely (significant medium to long-term adverse effects remain: oxidation of residues, elevation of homocysteine, glutathione collapse between 50 and 98 %, problems with the metabolism of vitamin B6 and the neurotransmitters produced in the Enteric Nervous System, in particular 50 % of dopamine and 95 % of serotonin - not protected by the barrier preventing carbidopa from entering the brain -, overloading of the liver, alteration of the mitochondrial I complex, etc. )

3) The same happened with the relationship between saturated fats and cardiovascular disease, a real dogma since the Keys studies in the 1950s and whose hypothesis was "confirmed" by thousands of studies over the next 50 years. Recently several studies have found no relationship, but rather the opposite (Siri-Tarino 2010; Dehghan 2017 or PURE study made public at the European Congress of Cardiological Societies in 2017). The repercussions of this "dogma", which proved to be false, on cardiovascular and neurological health will still have to be assessed in future studies. Already Rosser in 1993 or Ravnskov in 1993 warned in the British Journal of Medicine.


As with so many vitamins and nutrients, one must turn to somewhat older books to locate studies that point to some issues of interest, as well as the more recent studies that are revolutionizing the world of Parkinson's in theory. Unfortunately, not yet in everyday clinical practice.


Studies.

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

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

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

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.

Hughes (2016). Intake of antioxidant vitamins and risk of Parkinson’s disease. Movement Disorders.

Ide (2015). Lymphocyte vitamin C levels as potential biomarker for progression of Parkinson’s disease. Nutrition.

Kocot (2017). Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders? Nutrients.

Medeiros (2016). Iron and oxidative stress in Parkinson’s disease: an observational study of injury biomarkers. PLoS One.

Nagayama 2004. The effect of ascorbic acid on the pharmacokinetics of levodopa in elderly patients with Parkinson disease. Clin Neuropharmacol.

Quiroga (2014). Ascorbate- and zinc-responsive parkinsonism. Annals of Pharmacotherapy.

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.

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

Zhao (2019). Benefits of Vitamins in the Treatment of Parkinson's Disease.
Oxid Med Cell Longev