Articles

Home of the Parkinson's Improvement Programme

Here’s a selection of articles that document the research and rationale behind the programmes now using palmitoyl ascorbate:

Click a link, or scroll down to find the article

Excess cerebral TNF can cause neuronal inflammation

Excess neuronal TNF – a cytokine (messenger) molecule – can cause inflammation and amyloid deposition. This leads to consideration of anti-TNF agents as potential treatments for inflammation. Palmitoyl ascorbate is a strong anti-TNF substance or scavenger of free radicals – in this case an anti-oxidant. PIPmix contains palmitoyl ascorbate for that reason.

This article Effect of anti-TNF substances on CNS helps to explain what happens.

From the Journal of Neuroinflammation – open access – with thanks

Acylhomoserine lactone

Acyl homoserine lactone – signal or weapon or both? Implications for cancer treatment

Carmichael A. J. C. BDS

Abstract

The phenomenon of cell signalling or quorum sensing in bacterial populations was first suggested in 1970 by Nealson et al. Knowledge of its various forms has since developed rapidly as more accurate measuring and compound identification techniques have become available. The production of small, low molecular weight signalling molecules able to diffuse freely between the cellular and external environment continues until a minimum threshold level is reached indicative of an optimum population size – the quorum. It is seen as a way of controlling overgrowth that would lessen the efficiency of the population. These small molecules are of the general description of acyl homoserine lactones.

The recent exciting discovery of homocysteine lactones as a unique feature of aggressively dividing cancer cells suggests some parallels. The ability of homocysteine lactone to combine with dehydroascorbate to form the toxic compound 3-mercaptoproprionaldehyde results in selective cancer cell apoptosis. This finding raises the question as to whether the apparent signalling compound acyl homoserine lactone is also a bacterial weapon in view of the ascorbate present in all normal host cells and the similar possibility of formation of lethal or damaging compounds. It may be a major factor in the mechanism of initial bacterial attack on host cells. If the ‘weapon’ hypothesis is taken further the homocysteine lactone produced by the proliferating cancer cells could be a significant factor in the unselective breakdown of adjoining host cells during invasive tumour growth.

Article summary

Contrasts the conserved similarities of bacterial, human and malignant cell defences with the offensive mechanisms of bacteria and invasive carcinoma cells. Postulates that perceived bacterial signalling may be offensive. Suggests that a lipid soluble form of ascorbate may be effective against malignant growth.

Keywords: ascorbate, quorum-sensing, ulcer, cancer, lactone

Article focus

  • The conserved similarities in bacterial signalling / weaponry and invasive carcinoma attack
  • The potential for use of a simple food additive as potentiator of normal host cell defence.

Key message

Conserved mechanisms in bacteria and human cells are similar enough to provide a possible answer to treatment of diffuse or non-resectable cancer

Strength and limitation

  • A new approach focussing on supporting basic inbuilt cell defence mechanisms with a safe, low-cost substance
  • Potential life and cost savings
  • Case support for the hypothesis
  • Further study required

Discussion

Acyl homoserine lactones (AHSL) are small molecules produced by bacteria in circumstances of active growth under stress or competition (1) and their production appears to have a measurable relationship to the optimum concentration of the bacterial population in different circumstances (2). This relationship has been proposed as a feedback or signalling method to provide a measure of the optimum population of the particular bacteria in varying situations of stress level, nutrition, environment and level of competition present – the quorum.

It has been demonstrated that in a benign environment of adequate nutrition and no competitor strains, no measurable amounts of AHSL were produced by bacterial strains which had previously shown the ability to do so (1).

Although there is acknowledged difficulty in proving a negative conclusion it is suggested that the choice of production of AHSL or none is available to the bacteria and is influenced by their environmental conditions (1)(2)(3). This may reflect variations in virulence of the same strains dependent on the conditions. For example it might in some part explain the ability of MRSA organisms to cause no reaction on the skin surface where they are normally resident but to be aggressive when in a different sub-surface environment.

As long ago as 1982 M. E. Poydock (4)(5) demonstrated the effectiveness of dehydroascorbate against aggressive cancers in mice but the phenomenon was ignored for lack of explanation or because it was simply not believed.

The recent publication of the reasons for the selective apoptosis of cancer cells when dehydroascorbate is given (6) centres on the production within the tumour cells of homocysteine lactone (HCyL). This thiolactone has been shown to be singular to actively proliferating tumour cells (7) and in this respect the tumour cells resemble bacteria producing the similar AHSL whilst rapidly proliferating in a stressful environment.

The reaction of dehydroascorbate and HCyL within or near the tumour cell results in production of small amounts of a toxic substance, 3-mercaptoproprionaldehyde, which kills the cell (8,9).

Most mammalian normal cells contain ascorbic acid – Vitamin C – and it is transported across the cell membrane as dehydroascorbate via a glucose pathway (10). Compounds capable of donation of a thio-radical are found in normal cell constituents (11). Indeed, both AHSL and HCyL are formed from methionine. A plant precursor of ascorbic acid is galactono-1, 4-lactone.

Removal of the acyl group from AHSL to leave homoserine lactone (HSL) is a necessary prerequisite of formation of the toxic compound 3-hydroxypropionaldehyde (15) as a result of the reaction of dehydroascorbate and HSL. Acylases are produced by many bacteria and can be expected to be found in areas of multi-species infection. Deacylation is one of the means by which competing bacterial populations seek to gain advantage over their competitors by swamping the competing signals or employing host dehydroascorbate to destroy their rivals’ signal (or weapon) production (30).

There are suggestions of using these signalling or weapon systems as a means of bacterial control (11)(12)(13).

It is reasonable to propose that the production and dissemination of AHSL by bacteria could be construed to be a weapon in a mirror of the process in tumour cells whereby host cell metabolic damage, suspension of mitosis or apoptosis is the result. The use of the acyl group can be seen as a measure for protection of the bacterial signal against the ascorbate present in the host cells.

Host cell damage could result in an initial ulcerative lesion or abscess providing an attraction for opportunistic secondary infection or a source of nutrients for invasive proliferation by the primary bacterial attacker. The propionaldehyde produced from the reaction of dehydroascorbate and homoserine lactone is an inhibitor of cell metabolism and distorts normal processing (31) resulting in a backup of chemical detritus such as aldehydes. Aldehyde blockage is wasteful of nutrients and energy and inhibits cell function (32). If its production can be reduced or halted the processes can return to normal as the blockage is cleared. If the attack is powerful enough then apoptosis occurs.

It has been recently demonstrated that microglial metabolism in Alzheimer’s Disease is similarly damaged by herpes simplex virus (33) and that the virus ends up entombed in extra-cellular misfolded protein waste products known as amyloid (34). It is interesting that the process of formation of such extra-cellular waste follows the path of neurons and associated microglia from the gut to the brain as the virus spreads over a period of years (36). It is an attempt by the host cells to neutralise and eliminate an aggressor using the effect of the aggressor on cell metabolism to the best advantage. In this research (35) the virus is shown incorporated irretrievably into the mis-folded protein. As a result the normal cell protein breakdown is disrupted for lack of nutrients and energy and the cell malfunctions. In the nervous system these blockages of normal cell metabolism lead to long-term dysfunction such as Parkinson’s or Alzheimer’s Diseases. The changes are reversible in the early stages but end with eventual apoptosis of cells after long periods of disruption.

In the mirror of this process the production of HCyL and its emission from the invasive tumour cell into the area of contact with host tissue would provide an opportunity for formation of the toxic 3-mercaptopropionaldehyde around and within the cell membrane and subsequent apoptosis of the host cell. This toxicity would also affect the invading tissue but its greater speed of cell division would eventually result in the advantage in favour of the invader. The immediate interface between host and invasive tissue is acidic and oxygen deprived which are not good conditions for host cells and may advantage the invader (16)(17). A supply of nutrients such as glucose from the demolition of the well vascularised host tissue is a great benefit to the poorly vascularised invasive tissue (18). These factors are a plausible explanation for the apparently unselective invasive tissue damage caused by malignant tumours with the key differences of rapid growth and HCyL formation separating their behaviour from that of more benign growths. The mechanism of this change from benign to malignant may be simply the genetic changes needed for production of HCyL within the cells. It is reasonable to speculate that this might be influenced or induced by bacterial, fungal, viral or environmental involvement and in the presence of host genetic susceptibility. Archaea, a very resilient, sulphur tolerant genus of protobacteria, nocardia, various fungal infections, common viruses and Pseudomonas aeruginosa are candidates for investigation in this context (29).

The processes can be summarised:

Bacterial Weapon Host Defence
  • Acylhomoserine lactone Dehydroascorbate
  • Effect: (12)(13)(14) cell damage cell damage apoptosis
  • Outcome: invasion and proliferation abscess or ulcer secondary infection
Tumour Weapon Host defence
  • Homocysteine lactone Dehydroascorbate
  • Effect: apoptosis but with rapid replacement indiscriminate apoptosis
  • Outcome: invasion and rapid growth retreat with vital organ damage
  • If dehydroascorbate present in insufficient amounts tumour advances
  • Tumour retreats if dehydroascorbate present in sufficient amounts

These considerations lead to a suggestion that ascorbate in some form might be a potent cure for cancer either by itself or in combination with other agents (27)(28).

In view of the difficulty of supplying dehydroascorbate itself (requiring injection into the target) it is proposed that 6-O-palmitoyl-l-ascorbate (E-304) (PA) (known in the USA and Canada as ascorbyl palmitate) is a suitable candidate for consideration as an orally administered anti-cancer agent. It is lipid soluble and therefore hydrophobic and can be taken dissolved in olive oil, fish oil or butter – olive oil is in itself beneficial (19)(20). A daily intake of 1,000 mg PA gives the recommended maximum daily intake of 400 mg of ascorbate although some practitioners suggest much higher intakes. On breakdown it supplies palmitic acid and the ascorbic acid which on oxidation produces dehydroascorbate, the form in which ascorbate is transported across cell membranes by a glucose transport system. It is thus available in the immediate vicinity of the host cell in its most potent form.

PA is widely used as E-304 in products ranging from infant formula milk to beefburgers. It has been extensively studied and used in the cosmetics, agricultural and the food industries as an anti-oxidant and even as a component of edible anti-oxidant salad packaging now in development. It is available in nanopackages (21)(22) or simply as a powder. Safe human consumption in therapeutic quantities up to 1.6 g/day is well-established.

Palmitoyl ascorbate has known anti-angiogenic properties which contribute to its attraction as an anti-cancer agent (24). Anti-angiogenesis has been shown to be a valuable addition to the armoury of cancer treatments (25)(26). The formation of new vessels in an actively invasive tumour is less robust than in healthy tissue and restriction of it is a potent restraint on tumour development.

The lipophilic nature of PA is beneficial in the lipid-rich environment of the interface between invasive tissue and host. Increasing the concentration of lipid soluble ascorbate in the host cell / invasive cell interface in both bacterial and tumour invasion will act as a booster to the defence and result in reduced host cell damage whilst increasing the more fragile invader cell casualties.

A recent interesting suggestion is the use of porphyrins and ascorbate in tandem as a potential anti-cancer therapy (27). The chemical structure of porphyrin resembles a polymer of AHSL or HCyL and could block their formation or activity. Chemical variations of PA have been shown to have strong and selective effects on the hyaluronidases in bacterial and tumour populations leading to reduction (28). There is a pressing need for further investigation of this potentially useful treatment for invasive carcinomas.

Andrew Carmichael

No conflicts of interest arise from this work

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors

References

1 Signalling Molecules Production by Escherischia Coli and Campylobacter Jejuni
Sarah J Carmichael Ph.D
Ph.D thesis University of Central Lancashire June 2006
2 Profiling of acylated homoserine lactones of Vibrio anguillarum in vitro and in vivo: Influence of growth conditions and serotype
Buchholtz C, Nielsen KF, Milton DL, et al
Systematic and Applied Microbiology, 2006 29,6,433-445
3 Self-perception in bacteria: quorum sensing with acylated homoserine lactones
Fuqua C and Greenberg E P
Current Opinions in Microbiology 1998, 1,183–189
4 Inhibiting effect of dehydroascorbic acid on cell division in ascites tumours in mice
Poydock M E, Reikert D, Rice J et al
Experimental Cell Biology, 1982, 50 34–38
5 Influence of Vitamins C and B12 on the survival rate of mice bearing ascites tumour
Poydock M E, Reikert D and Rice J
Experimental Cell Biology, 1982, 50, 88–91
6 Synthesis of homocysteine thiolactone by methionyl-tRNA synthetase in cultured mammalian cells
Jabukowski H and Goldman E
FEBS Lett 1993 317.593–598
7 Metabolism of homocysteine thiolactone in human cell cultures
Jabukowski H
JBiol Chem, 1997 272.1835–1942
8 Mercaptopropionaldehyde from homocysteine: implications for Alzheimer’s Disease
Toohey J I
J Alz Dis, 2007 12.241–243
9 Dehydroascorbic acid as an anti-cancer agent
Toohey J I
Cancer Letters, Volume 263, Issue 2, 18 May 2008, Pages 164-169
10 New developments and novel therapeutic perspectives for Vitamin C
Li Y, Schellhorn H E
J Nutr, 2007 137.2171–2184
11 Cellular thiol pools are responsible for sequestration of cytotoxic reactive aldehydes: Central role of free cysteine and cysteamine
Wood PL, Khan MA and Moskal JR
Br Res 2008 1158.158-163
12 Infection Control by Antibody Disruption of Bacterial Quorum Sensing Signaling
Park J, Jagasia R, Kaufmann GF et al
Chemistry & Biology, 2007,14.10.1119-1127
13 Staphylococcus quorum sensing in biofilm formation and infection
Kong K-F, Vuong C, Otto M
Int J Med Microb 2006 296. 2-3.133-139
14 Dietary phytochemicals as quorum sensing inhibitors
Vattema DA, Mihalika K, Crixella SH et al
Fitoterapia 2007 78. 4. 302-310
15 Degradation of N-acylhomoserine lactones, the bacterial quorum-sensing molecules, by acylase
Feng Xu, Tony Byun, Heinz-Josef Dussen et al
Journal of Biotechnology 2003 101.1.89-96
16 Acidic pH enhances the invasive behavior of human melanoma cells
Martínez-Zaguilán R, Seftor EA, Seftor REB
Clinical and Experimental Metastasis 1996 14. 2.176-186
17 Metastases and their microenvironments: linking pathogenesis and therapy
Sierra A
DrResUp 2005 8. 4. 247-257
18 A model combining acid-mediated tumour invasion and nutrient dynamics
Bianchini L and Fasano A
j.nonrwa.2008. 10.1016/03.001
19 Oxidative stability and radical scavenging activity of extra virgin olive oils: An electron paramagnetic resonance spectroscopy study
V. Papadimitrioua, T.G. Sotiroudisa, A. Xenakisa et al
Analytica Chimica Acta 2006 573-574. 453-458
20 The antioxidant/anticancer potential of phenolic compounds isolated from olive oil
R. W. Owen, A. Giacosa, W. E. Hull et al
EJCan 2000 36.10.1235-1247
21 Development of ascorbyl palmitate nanocrystals applying the nanosuspension technology
Teeranachaideekul V, Junyaprasert VB, Souto EB et al
IntJ Phar, 2008 354.1-2.227-234
22 Multifunctional nanocarriers
Torchilin VP
Advanced Drug Delivery Reviews 2006 58.14.1532-1555
23 Ascorbic acid mobilizes endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: A putative mechanism for anticancer properties
International Journal of Biochemistry & Cell Biology 2006 38.12.2074-2081
24 Anti-angiogenic function of ascorbic acid and 6-O-palmitoyl ascorbate
Ashino H, Shimamura M, Suzuki N
VascPhar 45, 2006 3, e119-e120
25 Tumor Vasculature Targeted Therapies – Getting the Players Organized
Molema G, Meijer DKF and de Leij LFMH
Biochemical Pharmacology 1998 55.12.1939-1945
26 Tumor microvasculature and microenvironment: Targets for anti-angiogenesis and normalization
Fukumura D and Jain RK
Microvascular Research 2007 74. 2-3.72-84
27 Catalytic therapy of cancer with porphyrins and ascorbate
Rozanova (Torshina) N, Zhang JZ and Heck DE
CanLet 2007 252.2. 216-224
28 Novel 6-O-acylated vitamin C derivatives as hyaluronidase inhibitors with selectivity for bacterial lyases
Martin Spickenreither, Stephan Braun, Günther Bernhardt et al
Bioorganic & Medicinal Chemistry Letters 2006 16.20.5313-5316
29 Structural Basis for Natural Lactonase and Promiscuous Phosphotriesterase Activities
Elias M, Dupuy J, Merone L et al
Journal of Molecular Biology 2008 379.5.1017-1028
30 Revisiting quorum sensing: Discovery of additional chemical and biological functions for 3-oxo-N-acylhomoserine lactones
Kaufmann GF, Sartorio R, Lee S-H et al
31 The concept of “aldehyde load” in neurodegenerative mechanisms: Cytotoxicity of the polyamine degradation products hydrogen peroxide, acrolein, 3-aminopropanal, 3-acetamidopropanal and 4-aminobutanal in a retinal ganglion cell line
Wood PL, Khan MA and Moskal JR
j.brainres 2007.1145.150-156
32 Neurotoxicity of reactive aldehydes: The concept of “aldehyde load” as demonstrated by neuroprotection with hydroxylamines
Wood PL, Khan MA, Kulow SR et al
j.brainres.2006 1095.1.190-199
33 Herpes simplex virus infection causes cellular β-amyloid accumulation and secretase upregulation
Wozniak MA, Itzhaki RF, Shipley SJ et al
Neuroscience Letters 2007 429.2-3.95-100
34 Herpes Simplex Virus Type 1 and Alzheimer’s Disease: The Autophagy Connection
Itzhaki R, Cosby S L and Wozniak M M
Journal of Neurovirology
35 Herpes Simplex Virus Type 1 in Alzheimer’s Disease: The Enemy Within
Itzhaki R F and Wozniak M A
Journal of Alzheimer’s Disease 2008 13.393-405
36 Gastric α-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology
Braak H, de Vos RAI, Bohl J et al
Neuroscience Letters 2006 396.1.67-72

Copyright © 2013 Andrew Carmichael All rights reserved

Trigeminal Neuralgia

Trigeminal Neuralgia – a breakthrough in pain reduction

Andrew J C Carmichael BDS
Retired Dental Surgeon
Chair of Parkinson’s Improvement Programme
Email: andrew@brainhelp.info

Background

Trigeminal neuralgia (TN) is familiar to dental professionals as an intractable problem. Present drug treatments are frequently inadequate and have unpleasant side-effects.

A recent chance finding by a TN sufferer has been tested by a few volunteers and has been found to have great promise of almost complete alleviation of the pain without the use of conventional medication. It is brought to the notice of readers of this journal as an important potential treatment.

Introduction

A small charity (Parkinson’s Improvement Programme) has pioneered the use of ascorbyl palmitate (aka E-304 or palmitoyl ascorbate) (Changsha-Huir Biological Tech Co), a lipid soluble ester of ascorbic acid, in the treatment of Parkinson’s since 2007.

Ascorbyl palmitate is a safe food additive (LD-50 3,000 mg/kg) widely used in the food industry because of its powerful anti-oxidant properties. In combination with some oils and other food additives it has proved to be effective for some users in reducing or reversing some Parkinson’s symptoms. Despite having symptom altering properties it has been passed by the MHRA as not a drug but a borderline substance for an NHS clinical trial which is currently seeking funding and leadership.

In the course of this work it was suggested that the beneficial effects of ascorbyl palmitate might extend to improvement for chronic inflammation induced conditions such as Alzheimer’s and rheumatoid arthritis.

Discovery

A 47 year old female TN sufferer had recurrent right sided stabbing facial pain and paraesthesia which proved not to be controlled with tegretol or with gabapentin over a period of some weeks. Her MRI scan was clear and no apparent cause could be found. Knowing of the work with ascorbyl palmitate she elected to take a heaped teaspoonful of the powder (approx. 1.5 g) and a teaspoonful (approx. 5 ml) of fish oil (Lemon fish oil Higher Nature Ltd) daily both being stirred into a commercially available fruit yoghurt. At that time the patient was taking gabapentin as prescribed by her medical practitioner.

Results

The outcome of taking the ascorbyl palmitate (AP) was relief of paraesthesia and pain within a few hours. It was described as being like recovery from a dental local anaesthetic. The relief lasted some eight hours and a second intake of AP provided a good night’s sleep.

Since that outcome this patient continued with a daily intake of AP (but ceased to take gabapentin) for the next 18 months. At this stage the daily intake of AP was discontinued and the pain did not return for several weeks and then at a reduced intensity and over much shorter periods of time. AP has since been used intermittently as required without any other medication. It has been noticed that stress is a trigger. This patient was being treated with longterm levothyroxine 150 μg/day. Failure to take this for 48 hours resulted in return of the TN symptoms of pain and paraesthesia which ceased on resuming the medication. This possible connection requires follow-up in other TN cases.

As a result of this chance finding other cases have been offered the same AP treatment regime with positive outcomes.

Case histories

Consent to publish anonymous detail has been obtained from all.

  1. Female, 47, bilateral TN diagnosed 02/2014 triggered by cold wind, rain. History of shingles 01/2014 and 07/2014

    Her medical practitioner prescribed Pregabalin 150 mg 3x daily and paracetamol as required which did not relieve the pain.

    Commenced AP / fish oil 07/14 – gradually obtained relief over a week then found triggers no longer brought on pain; occasional short pain episodes since; has continued medication. This patient maintained a one month food intake and pain diary which suggested cheese products might increase short pain episodes. She is now pain free most days.

  2. Male, 80, edentulous,TN diagnosed 04/2013 triggered by chewing and swallowing. History of high BP, peripheral neuropathy, dyspepsia.

    Consultant neurologist prescribed Carbamazepine 200 mg 4x daily for TN. The patient was also on other medications.

    Commenced AP / fish oil 05/2014 – partial relief in a few days, total relief obtained in three weeks and able to eat and swallow freely. He continued medication and using the AP.

    In February 2015 he was hospitalised for complete washout of all medications and at this time he was stopped from using the AP/fish oil. After four weeks he had lost 10 kg in weight because the triggers for his TN were chewing and swallowing and thus eating was very painful. After release from hospital on no medication he resumed AP/fish oil and was pain free after two days and able to resume normal eating. He remains pain free to date.

  3. Female, TN diagnosed 2004, multiple triggers. History of Bell’s palsy 2002, Shingles 2002, R knee replacement 2014

    Commenced AP / fish oil 07/2014 – relief obtained and has continued using AP. No other medication.

  4. Female, 72, TN diagnosed 01/2013 various triggers. History of anxiety, IBS, cervical carcinoma 2004.

    Prescribed Gabapentin and diazepam 5 mg as required

    Commenced AP / fish oil 04/2013 – relief in a few days. Has used intermittently as required since. Continues on diazepam also.

  5. Female, 48, TN diagnosed 2013, strong perfumes, dehydration, tiredness or alcohol intake triggers. No relevant medical history

    Commenced AP/ fish oil 01/2014 and obtained rapid relief with no pain after a few days. Now only uses AP/ fish oil if pain recurs.

  6. Female, 41, TN diagnosed 11/2014, trigger not defined but has chronic bruxism with soft plastic occlusal cover nocte. No relevant medical history.

    Prescribed carbamazepine 1,200 mg daily changed to gabapentin

    Started AP/ fish oil 02/2015 pain relieved in a few days and remains controlled. Has tried stopping AP/ fish oil but still on gabapentin and pain is not controlled. Restarting AP/ fish oil relieved pain.

The experience of the initial patient over three years has been that the fish oil is not an essential part of the treatment which appears to work well without it.

AP is lipid soluble and the fish oil aids mixing into the yoghurt.

Conclusion

These histories suggest that ascorbyl palmitate may provide an inexpensive, safe, oral treatment for an otherwise often intractable condition.

In all the quoted cases full consent was obtained for anonymised publication. All were diagnosed and initially treated by their consultants or general practitioners and self-referred to this programme with the diagnosis assumed to be correct.

References which may be of interest

1 Ascorbyl palmitate as a carrier of ascorbate into neural tissues
Mieczyslaw Pokorski, Magdalena Marczak, Aneta Dymecka, Piotr Suchocki (2003)
Journal of Biomedical Science , 10(2), pp. .
2 Diverse effects of ascorbic acid and palmitoyl ascorbate on Helicobacter pylori survival and growth
M. Tabak, R. Armon, G. Rosenblat, E. Stermer and I. Neeman (2003)
FEMS Microbiology Letters , 224(2), pp. 247 – 253.
3 Anti-angiogenic function of ascorbic acid and 6-O-palmitoyl ascorbate
Hiromi Ashino, Mariko Shimamura and Naoko Suzuki (2006)
Vascular Pharmacology, B16, 18(), pp.
4 Trigeminal Neuralgia due to Arterialization of the Superior Petrosal Vein in the Context of Dural or Cerebral Arteriovenous Shunt
Robert T, Blanc R, Ciccio G, Smajda S, Redjem H, Fahed R, Piotin M
Clinical Neurology and Neurosurgery (2015), http://dx.doi.org/10.1016/j.clineuro.2015.08.004

The author declares no conflict of interests

This work has been funded by the Parkinson’s Improvement Programme UK Registered Charity no: 1137081

Copyright Andrew Carmichael 16.09.2015

Hyperhomocysteinemia

Hyperhomocysteinemia in l-dopa treated Parkinson’s disease patients: effect of cobalamin and folate administration

P. Lamberti, S. Zoccolella, E. Armenise, S. V. Lamberti, A. Fraddosio, M. de Mari, G. Iliceto and P. Livrea

Departments of Neurological Sciences, and Internal Medicine and Public Health–Hygiene Section, University of Bari, Bari, Italy

Correspondence to:
Prof. Paolo Lamberti
Department of Neurological Sciences
University of Bari
Ospedale Policlinico
P.zza G. Cesare 11
70124 Bari
Italy
Tel.: +39 08 0559 2321
Fax: +39 08 0547 8532
e-mail: lamberti@neurol.uniba.it)

Copyright 2005 EFNS

Keywords

cobalamin • folate • homocysteine • l-dopa • Parkinson’s disease

Abstract

Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment and dementia. l-dopa treatment may represent an acquired cause of hyperhomocysteinemia (HHcy), as evidenced by studies in rats as well as in Parkinson’s disease (PD) patients. Folate and cobalamin status also seems to influence the effects of l-dopa on plasma Hcy levels; therefore B-vitamins supplementation has been proposed to reduce the HHcy in l-dopa treated PD patients. Plasma Hcy, folate, and cobalamin levels were evaluated in 20 PD patients treated with l-dopa in the baseline condition and following a 5-week period of treatment with cobalamin and folate; results were compared with 35 controls.

Analysis of data revealed that Hcy levels were higher in l-dopa treated PD patients when compared with age- and sex-matched controls and that supplementation of the diet with cobalamin and folate is effective in reducing Hcy concentrations; these findings may have important implications in the treatment of PD patients who are potentially at risk for vascular diseases and cognitive impairment or dementia.

Eradicate! Eradicate !

A review of Helicobacter pylori and what it may do to you

Andrew J C Carmichael BDS

Abstract

A review of the available literature on Helicobacter pylori shows a wide range of conditions in which it is a factor as demonstrated either by improvement in the condition following eradication or by finding DNA of, or antigen to the bacterium.

The variety of conditions, many of which develop over decades, leads to serious consideration of the benefits of eradication of this infection as a matter of routine. Its importance could be equated with that of the eradication of TB, HPV or poliomyelitis and development of an appropriate vaccine would be valuable. In particular the involvement of Helicobacter pylori in long-term conditions affecting quality of life in old age will result in an ever increasing cost to health services in years to come.

Helicobacter pylori is a known carcinogen, recognised as such in 1994, and yet it is still tolerated.

There should be great concern about the gap in time between research findings and the practical medical use of them in the routine treatment of patients (1). Many of these treatment regimes have had quite a number of years to infiltrate the profession and yet apparently little is done to deal with an easily eradicated well-known pathogen.

Eradication of Helicobacter pylori, a common stomach bacterium, can greatly reduce your chances of suffering one or more of these diseases or in some cases, reduce the symptoms already noticed:

  • gastritis/ dyspepsia (2)(5)
  • gastric / duodenal ulcer (3)(4)(5)
  • gastric cancer (4)(5)(6)(7)(8)
  • high blood pressure (9)(10)(11)(12)
  • resolution of Syndrome X (heart and chest pain) (13)
  • altered lipid metabolism leads to obesity, heart attack and stroke (14)(15)(16)
  • iron deficiency anaemia (17)(18)
  • abnormal blood counts (neutrophils and monocytes) (19)(20)
  • neurological damage such as Parkinson’s, Alzheimer’s, MS, ME, optic nerve damage leading to blindness due to Vitamin B12 deficiency (21)(22)(23)(24)
  • chronic sub-clinical vitamin deficiency of A, B6, B12, C, E (25)(26)(27)(28)(29)(30)
  • skin conditions such as itchy, flaky, hard skin (31)(32)
  • rheumatoid arthritis (33)
  • chronic cholecystitis (34)
  • glaucoma (35)(36)
  • insulin resistance (37)
  • macular degeneration leading to blindness (38)
  • periodontal disease, tooth loss, reservoir of Hp infection in mouth (39)(40)(41)
  • some sexually acquired infections of nipples, vulva (42)

Many patients present with more than one of these conditions.

These are the subjects of a large number of peer-reviewed articles in respected journals over many years. ( reference list in numerical order )

Now it is time to do something about it.

Proposition

That ALL PD, AD, MS, medical and gastroenterology surgical patients should be tested for Helicobacter sp (43) and appropriate eradication commenced as a matter of routine using antibiotics with preceding probiotics (Bifidus and lactobacillus) to maintain a normal balance of beneficial gut bacteria (50)(51). This should be in addition to continuing dietary supplementation with omega-3 oils and / or fish oils and vitamin supplements as appropriate.

Reason for study

This study was initiated because of an interest in the results of work showing an improvement in the condition of some patients with Parkinson’s Disease (PD) following total eradication of Helicobacter pylori. In some cases this improvement amounted to regression of the condition (22)(23). It soon became apparent that the range was far wider than at first realised and the significance of the infection for health care costs throughout ever lengthening lives became obvious.

Equally it became apparent that hospital trusts can make considerable cost savings in gastroenterology by using probiotics prior to surgical treatment and by early eradication of Helicobacter thus reducing the development of conditions expensive to treat (50)(51)

Eradicating Helicobacter pylori will reduce the amount of antigen to it which circulates in blood and which has been suggested as the cause of death of sensitive long-axon nerve cells possibly because it stimulates platelet activity. This is a putative cause of neuropathies (49).

A possible solution

There is a food additive widely used in the processed food industry and therefore already of proven safety for human consumption.

6-O-palmitoyl-l-ascorbate, (E 304), (PA) is a lipid-soluble variant of Vitamin C (ascorbic acid). It is already in use in anti-wrinkle creams, infant formula milk, beefburgers (as an antioxidant preventing ‘greying’ of the meat) and is used by bodybuilders to add collagen to their intestinal and over-developed muscles. It also has the effect of reducing the formation of new blood vessels which may be relevant in macular degeneration and tumour restraint.

It is known to eradicate Helicobacter in vitro more efficiently than antibiotics even in low concentrations. In vivo its lipid solubility would make it able to penetrate the lipid based biofilm with which Helicobacter surrounds itself in the gastric mucosa. PA is a powerful anti-oxidant and can provide a source of ascorbate to replace the Vitamin C lost to the Helicobacter infestation which uses ascorbic acid as a nutrient thus denying it to the host (26)(27)(28). Ascorbate is essential for tissue repair and this lack of repair in subclinical chronic Vitamin C deficiency accounts for many of the disease effects listed above. It also provides a source of lipid useful in the repair process.

Concentrations of this Vitamin C ester are found up to 8 times that of ‘ordinary’ Vitamin C in the brain, very relevant in neuropathies. The suggested daily intake of this powder is 5 x 200 mg (44)(45)(46). It should be investigated as a means of gentle eradication of Helicobacter pylori in vivo because of its lack of side effects and proven safety as a widely used additive to a large range of foods.

Conclusion

Eradication of Helicobacter pylori has profound lifelong health benefits and is cost effective compared to the long term costs of resultant ill-health if it is allowed to persist. It should be a matter of routine in medical practice to test for it and initiate eradication.

References regarding Helicobacter pylori eradication and food additives

1 The Translation of Helicobacter pylori Basic Research to Patient Care
Peter B. Ernst, David A Peura and Sheila E. Crowe
Gastroenterology Volume 130, Issue 1, January 2006, Pages 188 – 206
2 The bidirectional communication between neurons and mast cells within the gastrointestinal tract
Luc Van Nassauw, Dirk Adriaensen and Jean-Pierre Timmermans
Autonomic Neuroscience doi: 10.1016/j.autneu.2006.10.003
3 Critical role of an endogenous gastric peroxidase in controlling oxidative damage in H. pylori-mediated and non-mediated gastric ulcer
Mrinalini Bhattacharjee, Samir Bhattacharjee, Arnab Gupta and Ranajit K. Banerjee
Free Radical Biology and Medicine Volume 32, Issue 8, 15 April 2002, Pages 731 – 743
4 Helicobacter pylori infection, not gastroesophageal reflux, is the major cause of inflammation and intestinal metaplasia of gastric cardiac mucosa
John R. Goldblum M.D., Joel E. Richter M.D., Michael Vaezi M.D., Gary W. Falk M.D., Thomas W. Rice M.D. and Richard M. Peek M.D.
The American Journal of Gastroenterology Volume 97, Issue 2, February 2002, Pages 302 – 311
5 Serum and plasma concentration of oxidant and antioxidants in patients of Helicobacter pylori gastritis and its correlation with gastric cancer
Shruti S. Khanzode, Suchet D. Khanzode and Ganesh N. Dakhale
Cancer Letters Volume 195, Issue 1, 30 May 2003, Pages 27 – 31
6 Carcinogenic role of tumor necrosis factor-alpha inducing protein of Helicobacter pylori in human stomach
Suganuma, Masami; Kuzuhara, Takashi; Yamaguchi, Kensai; Fujiki, Hirota
Journal of Biochemistry and Molecular Biology Volume 39, Issue 1, January 31, 2006, Pages 1 – 8
7 Will eradication of Helicobacter pylori infection influence the risk of gastric cancer?
Richard H. Hunt FRCP, FRCP(C), FACG
American Journal of Medicine Supplement Volume 117, Issue 5, Supplement 1, 6 September 2004, Pages 86 – 91
8 Can gastric cancer be prevented by Helicobacter pylori eradication?
Peter Malfertheiner, Professor, Lucia C Fry, Consultant and Klaus Munkenuller, Consultant
Best Practice and Research Clinical Gastroenterology Volume 20, Issue 4, 2006, Pages 709 – 719
9 Eradication of Helicobacter pylori infection improves blood pressure values in patients affected by hypertension
Migneco, Alessio; Ojetti, Veronica; Specchia, Lucia; Franceschi, Francesco; Candelli, Marcello; Mettimano, Marco; Montebelli, Rita; Savi, Luigi; Gasbarrini, Giovanni
Helicobacter Volume 8, Issue 6, December 2003, Pages 585 – 589
10 Prevalence of Helicobacter pylori infection in coronary artery disease and effect of its eradication on coronary lumen reduction after percutaneous coronary angioplasty
Kowalski M.; Konturek P.C.; Pieniazek P.; Karczewska E.; Kluczka A.; Grove R.; Kranig W.; Nasseri R.; Thale J.; Hahn E.G.; Konturek S.J.
Digestive and Liver Disease Volume 33, Issue 3, 2001, Pages 222 – 229
11 A link between Helicobacter pylori and/or Chlamydia spp. infections and atherosclerosis
Magdalena Chmiela, Magdalena Kowalewicz-Kulbat, Anita Miszczak, Monika Wisniewska, Tomas Rechcinski, Katarzyna Kolodziej, Jaroslaw Kasprzak, Torkel Wadstrom and Wieslawa Rudnicka
FEMS Immunology and Medical Microbiology Volume 36, Issue 3, 25 May 2003, Pages 187 – 192
12 Helicobacter pylori (H. pylori) infection in coronary artery disease: influence of H. pylori eradication on coronary artery lumen after percutaneous transluminal coronary angioplasty. The detection of H. pylori specific DNA in human coronary atherosclerotic plaque
Kowalski, M
Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society Volume 52, Issue 1, Supplement 1, August 2001, Pages 3 – 31
13 Resolution of Syndrome X after eradication of virulent CagA-positive Helicobacter pylori
Nocente, R; Gentiloni, N; Cremonini, F; Giorgi, A; Serricchio, M; Santoliquido, A; Gasbarrini, G; Gasbarrini, A
Southern Medical Journal Volume 93, Issue 10, October 2000, Pages 1022 – 1023
14 Helicobacter pylori is associated with modified lipid profile: impact on lipoprotein(a)
G. Chimienti, F. Russo, B. L. Lamanuzzi, M. Nardulli, C. Messa, A. Di Leo, M. Correale, V. Gianuzzi and G. Pepe
Clinical Biochemistry Volume 36, Issue 5, July 2003, Pages 359 – 365
15 Does eradication of Helicobacter pylori infection help normalise serum lipid and CRP levels?
Kanbay M.; Gur G.; Yucel M.; Yilmaz U.; Boyacioglu S.
Digestive Diseases and Sciences Volume 50, Issue 7, 2005, Pages 1228 – 1231
16 Association between chronic Helicobacter pylori infection and acute ischemic stroke: Fukuoka Harasanshin Atherosclerosis Trial (FHAT)
Yasunori Sawayama, Iwao Ariyama, Maki Hamada, Shigeru Otaguro, Takao Machi, Yuji Taira and Jun Hayashi
Atherosclerosis Volume 178, Issue 2, February 2005, Pages 303 – 309
17 A hematologist’s view of unexplained iron deficiency anemia in males: Impact of Helicobacter pylori eradication
Chaim Hershko, Mara Ianculovich and Moshe Souroujou
Blood Cells, Molecules and Diseases doi 10.1016/j.bcmd.2006.09.006
18 The clinical importance of hypochlorhydria (a consequence of chronic Helicobacter infection): Its possible etiological role in mineral and amino acid malabsorption, depression, and other syndromes
R. E. Cater 11
Medical Hypotheses Volume 39, Issue 4, December 1992, Pages 375 – 383
19 Helicobacter pylori eradication decreases blood neutrophil and monocyte counts
Kondo Y.; Joh T.; Sasaki M.; Oshima T.; Itoh K.; Tanida S.; Kataoka H.; Ohara H.; Nomura T.; Itoh M.
Alimentary Pharmacology and Therapeutics, Supplement Volume 20, Issue1, 2004, Pages 74 – 79
20 Effect of Helicobacter pylori eradication in patients with chronic idiopathic thrombocytopenic purpura – A randomised controlled trial
Suzuki T.; Matsushima M.; Masui A.; Watanabe K.-L; Takagi A.; Ogawa Y.; Shirai T.; Mine T.
American Journal of Gastroenterology Volume 100, Issue 6, 2005, Pages 1265 – 1270
21 Alzheimer’s disease and Helicobacter pylori infection: Defective immune regulation and apoptosis as proposed common links
Jannis Kountouras, Emmanuel Gavalas, Christos Zavos, Christos Stergiopoulos, Dimitrios Chatzopolous, Nikolaos Kapetanakis and Dimitrios Gisakis
Medical Hypotheses Volume 68, Issue 2, 2007, Pages 378 – 388
22 Role of inflammation in gastrointestinal tract in aetiology and pathogenesis of idiopathic parkinsonism
Clive Weller, Norman Oxlade, Sylvia M. Dobbs, R. John Dobbs, Andre Charlett and Ingvar T. Bjarnason
FEMS Immunology and Medical Microbiology Volume 44, Issue 2, 1 May 2005, Pages 129 – 135
23 Link between Helicobacter pylori infection and idiopathic parkinsonism
S.M. Dobbs, R.J. Dobbs, C. Weller and A. Charlett
Medical Hypotheses Volume 55, Issue 2, August 2000, Pages 93 – 98
24 Epidemic Optic and Peripheral Neuropathy in Cuba: A Unique Geopolitical Public Health Problem
Thomas R. Hedges 111, MD, Michio Hirano, MD, Katherine Tucker, PHD, and Benjamin Caballero, MD, PHD
Survey of Ophthalmology Volume 41, Number 4, January-February 1997
25 Plasma levels of antioxidant vitamins C and E are decreased in vascular parkinsonism
George P. Paraskevas, Elizabeth Kapaki, Olga Petropolou, Maria Anagnostouli, Vasileious Vagenas and Constantine Papageorgiou
Journal of The Neurological Sciences Volume 215, Issues 1-2, 15 November 2003, Pages 51 – 55
26 Influence of gastric juice pH on the metabolism of vitamin C in gastric mucosa and juice
Safranow K, Korzonek M, Dziedziejko V, Jacubowska K, Sulzyc-Bielicka V, Domanski L, Ciechanowski K, Chlubek D.
Pol Merkur Lekarski, 2006 Feb; 20(116); Pages 168 – 172
27 Relationship of Helicobacter pylori CagA(+) status to gastric juice vitamin C levels
Rokkas T.; Liatsos C.; Petridou E.; Karameris A.; Ladas S.D.; Raptis S.A.
European Journal of Clinical Investigation Volume 29, Issue 1, 1999, Pages 56-62
28 Omeprazole and dietary nitrate independently affect levels of Vitamin C and nitrite in gastric juice
Craig Mowat, Andrew Carswell, Angela Wirz and Kenneth E. L. McColl
Gastroenterology Volume 116, Issue 4, Pages 813 – 822
29 Investigation of Helicobacter pylori ascorbic acid oxidating activity
Lars Odum and Leif P. Andersen
FEMS Immunology and Medical Microbiology Volume 10, Issues 3-4, February 1995, Pages 289 – 294
30 Vitamin B12, demyelination, remyelination and repair in multiple sclerosis
Ariel Miller, Maya Korem, Ronit Almog and Yanina Galboiz
Journal of the Neurological Sciences Volume 233, Issues 1-2, 15 June 2005, Pages 93 – 97
31 Tumor initiating activity of Helicobacter pylori water extract on mouse skin carcinogenesis
Takeshi Ishikawa, Norimasa Yoshida, Harukuni Tokada, Eiichiro Ichiishi, Masashi Kuchide, Satoshi Kokura, Yuji Naito, Shinya Toyokuni, Hoyoko Nishino and Toshikazu Yoshikawa
Cancer Letters Volume 191, Issue 1, 28 February 2003, Pages 41 – 47
32 Therapeutic effects of the antibacterial treatment on intractable skin diseases in Helicobacter pylori-positive patients
Mikihisa Sakurane, Matsunaka Masahiro, Koji Uede, Akiko Shiotani, Shingo Nishioka
Department of Dermatology; Second Department of Internal Medicine, Wakayama Medical University, Japan (Poster Display P249)
33 Eradication of Helicobacter pylori may reduce disease severity in rheumatoid arthritis
Zentillin, P; Seriolo, B; Dulbecco, P; Caratto, E; Iiritano, E; Fasciolo, D; Bilardi, C; Mansi, C; Testa, E; Savarino, V
Alimentary Pharmacology and Therapeutics Volume 16, Issue 7, July 2002, Pages 1291 – 1299
34 Helicobacter pylori and other Helicobacter species in gallbladder and liver of patients with chronic cholecystitis detected by immunological and molecular methods
Apostolov E.; Abu Al-Soud W.; Nilsson I.; Kornilovska I.; Usenko V.; Lyzogubov V.; Gaydar Y.; Wadstrom T.; Ljungh A.
Scandinavian Journal of Gastroenterology Volume 40, Issue 1, 2005, Pages 96 – 102
35 Eradication of Helicobacter pylori may be beneficial in the management of chronic open-angle glaucoma
Kountouras J.; Mylopoulos N.; Chatzopoulos D.; Zavos C.; Boura P.; Konstas A.G.P.; Venizelos J.
Archives of Internal Medicine Volume 162, Issue 11, 10 June 2002, Pages 1237 – 1244
36 Induction of apoptosis as a proposed pathophysiological link between glaucoma and Helicobacter pylori infection
Jannis Kountouras, Christos Zavos and Dimitrios Chatzopoulos
Medical Hypotheses Volume 62, Issue 3, March 2004, Pages 378 – 381
37 The effect of Helicobacter pylori on insulin resistance
Aydemir S.; Bayraktaroglu T.; Sert M.; Sokmen C.; Atmaca H.; Mungan G.; Gun B.D.; Borazan A.; Ustundag Y.
Digestive Diseases and Sciences Volume 50, Issue 11, 2005, Pages 2090 – 2093
38 Association of Helicobacter pylori with central serous chorioretinopathy: hypotheses regarding pathogenesis
Christiano Giusti
Medical Hypotheses Volume 63, Issue 3, 2004, Pages 524 – 527
39 Are dental plaque, poor oral hygiene, and periodontal disease associated with Helicobacter pylori infection?
Anand P.S.; Nandakumar K.; Shenoy K.T.
Journal of Periodontology Volume 77, Issue 4, 2006, Pages 692 – 698
40 Expression cloning of a periodontitis-associated apoptotic effector, cagE homologue, in Actinobacillus actinomycetemcomitans
Yen-Tung A. Teng, and Wenqui Hu
Biochemical and Biophysical Research Communications Volume 303, Issue 4, 18 April 2003, Pages 1086 – 1094
41 Persistence of Helicobacter pylori in the oral cavity after systemic eradication therapy
Gebara E.C.E.; Faria C.M.; Pannuti C.; Chehter L.; Mayer M.P.A.; Lima L.A.;
Journal of Clinical Periodontology Volume 33, Issue 5, May 2006, Pages 329 – 333
42 Some fibrocystic breast change may be caused by sexually transmitted H. pylori during oral nipple contact: Supporting literature and case report of resolution after gut H. pylori eradication treatment
R.E.Kast
Medical Hypotheses doi:10.1016/j.mehy.2006.09.050 (article in press)
43 Helicobacter pylori “Test and Treat” or Endoscopy for Managing Dyspepsia: An Individual Patient Data Meta-analysis
Alexander C. Ford, Michelle Qume, Paul Moayyedi, Nicolas L.A. Arents, Annmarie T. Lassen, Richard F.A. Logan, Kenneth E.I. McColl, Paul Myres and Brendan C. Delaney
Gastroenterology Volume 128, Issue 7, June 2005, Pages 1838 – 1844
44 Palmitoyl ascorbate: Selective augmentation of procollagen mRNA expression compared with L-ascorbate in human intestinal smooth muscle cells
Rosenblat G.; Willey A.; Zhu Y.-N.; Jonas A.; Diegelmann R.F.; Neeman I.; Graham M.F.
Journal of Cellular Biochemistry Volume 73, Issue 3, 15 May 1999, Pages 312 – 320
45 Diverse effects of ascorbic acid and palmitoyl ascorbate on Helicobacter pylori survival and growth
M.Tabak, R.Armon, G. Rosenblat, E. Stermer and I. Neeman
FEMS Microbiology Letters Volume 224, Issue 2, 29 July 2003, Pages 247 – 253
46 Ascorbyl Palmitate as a Carrier of Ascorbate into Neural Tissues
Mieczyslaw Pokorski, Magdalena Marczak, Aneta Dymecka, Piotr Suchocki
Journal of Biomedical Science Volume 10, Issue 2, 2003
47 Multiple Effects of Trehalose on Protein Folding In Vitro and In Vivo
Mike A. Singer and Susan Lindquist
Molecular Cell Volume 1, Issue 5, April 1998, Pages 639 – 648
48 Aggregation mechanism of polyglutamine diseases revealed using quantum chemical calculations, fragment molecular orbital calculations, molecular dynamics simulations, and binding free energy calculations
Koki Tsukamoto, Hideaki Shimizu, Takashi Ishida, Yutaka Akiyama and Noboyuki Nukina
Journal of Molecular Structure: THEOCHEM Volume 778, Issues 1-3, 11 December 2006, Pages 85 – 95
49 Cholesterol synthesis inhibitors protect against platelet-activating factor-induced neuronal damage
Clive Bate, Louis Rumbold and Alun Williams
Journal of Neuroinflammation Volume 4, Issue 5, 18 January 2007
50 Probiotics and Helicobacter pylori
C.Felley MD, Associate physician, instructor and P. Michetti MD, Professor and chief
Best Practice and Research Clinical Gastroenterology Volume 17, Issue 5, October 2003, Pages 785 – 791
51 Effect of probiotics on intestinal regrowth and bacterial translocation after massive small bowel resection in a rat
Jorge G. Mogilner, Isaac Srugo, Michael Lurie, Ron Shaoul, Arnold G. Coran, Eitan Shiloni, and Igor Sukhotnik
Journal of Pediatric Surgery Volume 42, Issue 8, August 2007, Pages 1365 – 1371

Andrew J C Carmichael is a retired Dental Surgeon with a particular interest in microbiology, nutrition and neuropathies – primarily Parkinson’s Disease

Relevant interests:

  • Former Governor of Lancashire Teaching Hospitals NHS Foundation Trust
  • Former Chair Preston Branch of the Parkinson’s Disease Society