Why PIP ?

Home of the Parkinson's Improvement Programme

The first consideration was the generally accepted situation that Parkinson’s Disease is unique in originating in brain and only affecting that organ. This seemed unlikely and the following was drawn up in 2004 in conjunction with a marine engineer with long experience of repairs to engines at sea. His comment “At least you can get to the engine parts to service them” emphasised the importance of circulation in the repair and renewal process in the brain.

All long term systems require:

  • Adequate design and structure
  • Sufficient spare capacity to function despite component failure and lack of repair
  • Possibility of repairs in event of failure beyond spare capacity
  • Availability of spare parts at the area of need and energy to fit them
  • Removal and safe storage or disposal of redundant or failed parts

Humans are a long term system!!

Therefore ALL these factors apply to us and in the gradual development of Parkinson’s or other neuropathological syndromes these combine as shown below. Some of these qualities are genetically determined, i.e. inherited.

Quality of nervous system including overcapacity and collateral paths and innate ability to repair

Quality of circulatory system including thickness of vessel walls, layout and collateral routes and heart efficiency

All these are important !!

Quality of energy supply depends on circulation to deliver and replenish and also remove waste products

Quality of nutrient supply depends on gut efficiency, absorption, toxin production, competition for nutrients and good circulation to deliver

Long term gradual failure of one or more of these is likely to result in slowly increasing brain damage only apparent after many years when all spare capacity has been used up and sufficient self-repair is not possible.

Following this line of thought my attention was drawn to the work of Drs Sylvia and John Dobbs et al on the improvement in PD following eradication of Helicobacter pylori, a noxious stomach bacterium ( 1, 2 ). They came to address the Preston Branch of the PDS (now Parkinson’sUK) of which I was Chair. Their paper published in 2000 had been ignored by all those who were still convinced it was solely a ‘brain’ problem. Video of their patients’ improvement was a powerful argument in favour of their theories. A later paper in 2005 reinforced their results but was similarly ignored or ridiculed by the establishment. The PDS had refused to support their work.

Further reading around H pylori and PD in general, together with discussion and proof-reading my daughter’s 2006 PhD thesis (several times!) on ‘Signalling mechanisms in E. coli and Campylobacter’ led to a growing feeling that the connection between gut health and brain health was obvious. Knowing the inadequacies of antibiotics and the side-effects of the eradication treatment for H. pylori I read widely (reviewing some 70,000 alerts from Science Direct, reading several thousand abstracts and fully reading several hundred full articles). This constant review continues.

Using this excellent facility provided for me by University of Central Lancashire to check out references it came to my notice that a group in Israel had published work ( 3 ) on eradication of H pylori in vitro showing 85% efficiency for antibiotics and an astonishing efficiency of 100% for 6-O-palmitoyl-l-ascorbate, a lipid soluble ester of Vitamin C (ascorbic acid). The concentration required was as low as 0.4 micromol / litre (molecular weight 440). The efficacy is ascribed to the ability of the lipid-soluble ester to penetrate the greasy coating (biofilm) produced by the H. pylori. From the assumption that the stomach volume might be one litre, an intake of 75 mg was considered suitable. Inefficiency in solubility of the light, fluffy powder in food and masking of it by stomach contents led to a decision to suggest 200 mg as a proper amount to use in a trial daily intake. This was weighed out and correlated to a level mustard spoonful, a convenient measure for home use.

Palmitoyl ascorbate (E 304) is accepted as a safe food additive and is used in beefburgers as an anti-oxidant to prevent greying in store, used in bakery products, face creams, salad preservation, infant formula milks and used by bodybuilders as a collagen stimulant in muscle building. It is known in the USA as ascorbyl palmitate.

During this reading and study it became apparent that there were advantages in using probiotics as a buffer prior to the eradication treatment for H. pylori ( 4, 5 ). Many references are available to support this position. The intention is to boost the Bifidus and Lactobacillus strains which are damaged as a side effect of the antibiotics used for eradication of H. pylori and thus maintain gut health. Advice from Professor Judd at the University of Central Lancashire was that a proven ‘system’ in the form of Danone fruit layer yoghurt and Actimel l. casei drink was appropriate for the purpose so this became part of the advice to participants. This combination also tends to prevent constipation. Conveniently the yoghurt is a very good vehicle for mixing with the flocculant palmitoyl ascorbate powder to assist with ingesting it. The powder can also be taken in a buttered bread sandwich or dissolved in olive oil. In small quantities eg. 20 mg it can be inhaled into the nostrils.

Literature also suggested that the provision of fish oils/omega-3 oils would be beneficial in providing the repair materials for brain to recover ( 6, 7, 8 ). A particularly interesting paper demonstrated the connection between mast cells along the length of the gut and the brainstem so arranged as to be able to govern the absorption of nutrients in balance with requirements determined by sensors in the circulation ( 9, 10 ). This knowledge backs up work done by Dr Ruth Itzhaki on the propagation of virus through neurons in AD ( 11 ) and further work by others showing that the gut wall is made more permeable by the antigens of H pylori thus allowing permeation of virus, virions, prions or antigen from H pylori itself ( 12 ). This made the eradication of H pylori even more pressing.

Following trials of ingestion of probiotics and palmitoyl ascorbate on H pylori -ve (tested) and non-PD persons (as far as we know) i.e. myself, my partner and a friend, it was established that we had no side effects other than a feeling of wellness and in one case remission of a chronic urinary tract infection. Stopping and restarting the additives appeared to have no detrimental health effects other than temporary recurrence of the UTI. The study was started in February 2007 by enrolling interested friends with PD. Their early reports indicated an improvement in gut function, an improvement in speech clarity and volume (noted by others but not by the participants) and a feeling of wellbeing.

The recommended daily intake was set at :

  • Danone fruit layer yoghurt – one tub – prune suggested as appropriate
  • Actimel l. casei drink – one
  • Fish or omega 3 oil capsule 1000 mg – one – Boots cheapest found
  • 200 mg palmitoyl ascorbate powder – taken mixed in yoghurt or olive oil
  • 10 g trehalose

Participants were asked to sign consent forms and to report any positive or negative findings. The long term nature of the study was emphasised. Trehalose was included as reading the literature on Huntington’s had flagged it as a neuroprotective substance and indeed it is sold as such in the USA ( Neurocoat TM ) ( 13 ). The recommended amount was at the lower end of the intake usually suggested of 10-30 g daily. It is a fructose with 40% glucose equivalence. The rationale for use is that it has the ability to enhance the processing of misfolded proteins e.g. amyloid or synuclein.

Later in the study – after some months – a few participants dropped out claiming lack of any further improvement. It was notable that the speech improvement regressed following cessation of the additives. At about this time work was published suggesting that chronic inflammation in or around neurons was the cause of their demise or malfunction ( 13 ). Discussions with authors worldwide had hinted at this two years earlier and amyloid, Lewy bodies and synuclein dismissed as ‘garbage’, ‘landfill’ or merely waste products set aside as not being capable of processing in conditions of energy or nutrient shortage or vascular inadequacy.

A paper published in the Journal of Neuroinflammation supports this by showing the dramatic effect of using an established anti-inflammatory drug etanercept in AD with recovery of faculties from a demented state in only an hour following injection ( 14 ). Reduction of TNFalpha – an inflammation induced substance which is possibly also a neurotransmitter is proposed as the method of action.

Further support for the ‘inflammation’ view is provided by the observation of several PwP that diazepam (Valium) has a beneficial effect on dyskinesia. This is likely to be due to its effect of increasing formation of GABA with a consequent reduction in associated excess neurotransmission. An imbalance of various neurotransmitters is a very plausible explanation for the symptoms of PD and overload of one may contribute to underproduction of another or vice versa. In a long term chronic condition neurons may simply give up under the strain of inadequate supplies or uneven use. Neurotransmitters might normally be carefully targeted but in overload conditions this targeting could be lost.

This may explain the action of palmitoyl ascorbate which has been shown in one study to be eight times more effective at reaching the brain than conventional water soluble ascorbic acid ( 15 ). Any anti-inflammatory effect would be beneficial and antioxidants of various kinds have been shown to benefit PwP in several studies.

A trial participant took it upon herself to take the palmitoyl ascorbate five times a day with her normal PD meds as she had noticed it improved the onset of their action. Since then an increase of 25% in ‘on’ time and much improved efficacy of medication was reported together with increased vitality.

Another participant was notified of this and has reported return of his sense of smell and an ability to get small items out of his pocket – previously impossible. This improvement continues with a return of facial expression. [*see end of references for update.]

Further study is proceeding with a variation in the recommendations as follows :

  • Trehalose optional 5 g or 10 g daily. It may act as a vehicle for increased transport of ascorbate into cells by supporting the normal glucose channels and also acts to support normalisation of protein metabolism.
  • Palmitoyl ascorbate recommended as 4 or 5 X 200 mg daily. It can be taken in yoghurt, olive oil (better), a bread and butter sandwich and/or by inhaling the powder in SMALL quantities (about 20 mg). It is an excellent clearer of the nasal passages!
  • Addition of broccoli extract (sulforaphane) as a powerful anti-inflammatory. Ideally one tablet daily equivalent to 500 mg extract (2% sulforaphane content). Otherwise as before listed.

It is appreciated that this is anecdotal evidence but it is encouraging enough to suggest that a more structured and verifiable study would result in some relief to PwP at modest cost and with no licencing hurdles to its early adoption.

No conflicts of interest arise from this work

All patient involvement has been subject to informed and witnessed consent

Andrew Carmichael is a retired dental surgeon with a broad medical background and a long interest in the health of the whole person rather than specific systems.

References

1 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
2 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
3 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
4 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
5 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
6 Effect of probiotics on preventing disruption of the intestinal microflora following antibiotic therapy: A double-blind, placebo-controlled pilot study
Jennifer A.J. Madden, Susan F. Plummer, James Tang, Iveta Garaiova, Nigel T. Plummer, Mary Herbison, John O. Hunter, Takashi Shimada, Lei Cheng and Taro Shirakawa
International Immunopharmacology Volume 5, Issue 6, June 2005, Pages 1091 – 1097
7 Omega-3 fatty acids and antioxidants in neurological and psychiatric diseases: An overview
Marianna Mazza, Massimiliano Pomponi, Luigi Janiri, Pietro Bria and Salvatore Mazza
Progress in Neuro-Psychopharmacology and Biological Psychiatry Volume 31, Issue 1, 30 January 2007, Pages 12 – 26
8 Dietary supplementation of arachidonic and docosahexanoic acids improves cognitive dysfunction
Susumu Kotani, Eiko Sakaguchi, Shogo Warashina, Noriyuku Matsukawa, Yoshiyuki Ishikura, Yoshinobu Kiso, Manabu Sakakibara, Tanihiro Yoshimoto, Jianzhong Guo and Tetsumori Yamashima
Neuroscience Research Volume 56, Issue 2, October 2006, Pages 159 – 164
9 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
10 Hypothalamic sensing of fatty acids
Tony K T Lam, Gary J Schwartz and Luciano Rossetti
Nature Neuroscience 8, (2005), Pages 579-584
11 Infiltration of the brain by pathogens causes Alzheimer’s disease
R. F. Itzhaki, M. A. Wozniak, D. M. Appelt, B. J. Balin
Neurobiology of Aging, Volume 25, Issue 5, May-June 2004, Pages 619 – 627
12 Intracellular, Intercellular, and Stromal Invasion of Gastric Mucosa, Preneoplastic Lesions, and Cancer by Helicobacter pylori
Vittorio Necchi, Maria Elena Candusso, Francesca Tava, Ombretta Luinetti, Ulderico Ventura, Roberto Fiocca, Vittorio Ricci, Enrico Solcia
Gastroenterology, Volume 132, Issue 3, March 2007, Pages 1009 – 1023
13 Multiple Effects of Trehalose on Protein Folding In Vitro and In Vivo
Mike A. Singer and Susan Lindquist
Molecular Cell Volume1, Issue 5, April 1998, Pages 639 – 648
14 Rapid cognitive improvement in Alzheimer’s disease following perispinal etanercept administration
Edward L. Tobinick and Hyman Gross
Journal of Neuroinflammation 2008,5:2 doi: 10.1186/1742-2094-5-2
15 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

References

1 Hyperhomocysteinemia in l-dopa treated Parkinson’s disease patients: effect of cobalamin and folate administration
P. Lamberti a , S. Zoccolella a , E. Armenise b , S. V. Lamberti a , A. Fraddosio a , M. de Mari a , G. Iliceto a and P. Livrea
European Journal of Neurology Volume 12 Issue 5, Pages 365 – 368
Published Online: 24 Mar 2005

I regard the folic acid as a major factor in the programme and it is included from September 2008.

Sulforaphane references

1 Vitamin B12, folic acid, and the nervous system
Edward Reynolds (Epileptology Kings College)
Lancet Neurology 2006; 5; Pages 949 – 960
2 Methionine sulfoxide reductase A protects dopaminergic cells from Parkinson’s disease-related insults
Fang Lui, Jagadish Hindupur, Jamie L Nguyen, Katie J Ruf, Janyi Zhu, Jeremy L Schieler, Connie C Bonham, Karl V Wood, V Jo Davisson, Jean Christophe Rochet
Free Radical Biology and Medicine 2008

Andrew JC Carmichael BDS
November 2008