Archive for January, 2016

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Rheumatoid arthritis

References of interest

From Nature Medicine 5th August 2015

  • Germs and joints: the contribution of the human microbiome to rheumatoid arthritis pp839 – 841
    Geraint B Rogers
    doi:10.1038/nm.3916

    Rheumatoid arthritis (RA) is a debilitating autoimmune disorder, the etiology of which is poorly understood. A new study reveals dysbiosis in gut and oral microbiomes of affected individuals, potentially providing a basis for patient stratification and clues to pathophysiological mechanisms of RA onset and progression.

  • The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment pp895 – 905
    Xuan Zhang, Dongya Zhang, Huijue Jia, Qiang Feng, Donghui Wang et al.
    doi:10.1038/nm.3914

    The gut and oral microbiomes are altered in individuals with rheumatoid arthritis, and these changes can be used to stratify individuals for diagnostic and prognostic purposes.

Trigeminal neuralgia

Find some startling news of a possible treatment for this desperately painful condition. Look in the articles section of this site and scroll down

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

Palmitoyl ascorbate and cancer

Palmitoyl ascorbate (PA) is a strong anti-oxidant, is anti-angiogenic (reduces the formation of new blood vessels) and is the lipid-soluble form of Vitamin C. There are many ways these properties are useful and it is likely that PA can be useful in combatting all cancers. The article ‘Acylhomoserine lactone’ on this site explains in more detail its action as it builds up the ascorbate concentration in the host cells to combat invasive tumours. The effect of reduction in the formation of new blood vessels by an active tumour is also useful in slowing tumour development.

Recent work with cell cultures at the University of Central Lancashire has shown that palmitoyl ascorbate can wipe out glioblastoma cells in vitro. Glioblastoma is the most aggressive form of brain tumour and often found in young children. If this could be slowed down or stopped by a substance taken by mouth it might mean less or no surgery and a greatly improved recovery rate from this devastating condition. The work needs to be taken up by a University equipped for animal testing of the substance.

Rheumatoid arthritis (RA)

RA diagnosed 2001 resulted by 2011 in having finger joints so stiff and swollen that small change could not be sorted or removed from a purse on purchase of goods. To pay a bill notes had to be handed over and the open purse held out to get change put in by the shop assistant. The changing of gears was difficult. Cleaning was difficult as was carrying small items or drinks.

Started on Palmitoyl ascorbate 2 grams/day (a teaspoonful) and lemon fish oil (a teaspoonful) and in 48 hours my hands were better than they had been for ten years. The swelling was down and my joints moved as they should! No medications had even got near to this result.

Four years later this condition is stable but I still take the powder and oil to keep it that way.

Rheumatoid arthritis

Recent experience of the use of lemon fish oil and palmitoyl ascorbate in a case of rheumatoid arthritis of some ten years standing has suggested that this might be a novel and highly effective treatment for this difficult condition.

Palmitoyl ascorbate has been in use as part of a treatment for Parkinson’s Disease for the past 8 years. It is used widely in the food industry as an anti-oxidant and we are using it at a very safe daily intake level. It has other names: Vitamin C palmitate; ascorbyl palmitate; E-304 – all the same thing.

We suggest a daily intake of 1 – 2 grammes (a heaped teaspoonful) together with 5 ml of Lemon fish oil.

Palmitoyl ascorbate is lipid-soluble whereas Vitamin C (ascorbic acid) is water soluble. This difference in solubility enables this compound to be more effective in some situations than natural Vitamin C. For example, in laboratory conditions it is 100 % lethal to Helicobacter pylori – a nasty stomach dwelling bug.

The mechanism of action of Lemon fish oil and palmitoyl ascorbate in rheumatoid arthritis is not known although it seems likely to be some combination of antibacterial activity together with some damping down of chronic inflammation.

Case Notes

Year of birth: 1951

PD diagnosed: 1999

Symptoms:

  • Mild, until neck operation 2009 then rapid deterioration, Bell’s palsy and eczema July 2010
    Gait unsteady, poor balance, walking stiffly on tiptoe with support, speech impaired and depression, severe constipation (common PD symptom).
  • 2010 (July) Started on PIPmix, B12 and probiotics
  • 2010 (August) Feels better, steadier on feet, better balance with armswing when walking, constipation cured, back in his workshop able to work on car. Speech more normal.
    Takes his wife breakfast in bed upstairs carrying tray with no spillage.
  • 2010 (December) Reduced prescribed medication by 50 %, has more energy. Wife says he spends all day in workshop (keeps and maintains 5 old cars)
  • 2011 (February) Walking well, more energy, good balance, delighted.
  • 2011 (May) Servicing all 5 cars using pit in garage, walking well, feels fine
  • 2011 (October) Extending workshop himself. Walking well, feels fine. Consultant at routine visit describes his Parkinson’s as ‘mild’.
  • 2013 (April) Still in good health and very active (14 years after diagnosis) Cleared large area of rough land with hand tools.
  • 2014 (February) Trialled a modified PIPmix formulation and found a massive improvement in gait and balance. Able to walk without fear of falling. Also found better sleep and less dyskinesia. This continues (January 2015)

Summarised by Andrew Carmichael from case notes

Case History

Yr of birth: 1950

History:

  • Fractures following accident 1994 – subsequent stress/fatigue/tremor
  • PD diagnosed: 1999
  • Retired from teaching 2001
  • 2002 – 2007 Obsessive Compulsive Disorder (OCD) following agonist treatment which was eventually discontinued.
    Gait unsteady even using walking stick, unable to ride cycle or play musical instruments
  • 2008 (October) started on Parkinson’s Improvement Programme
  • 2008 (November) after three weeks ran for 20 minutes and could ride mountain bike again
  • 2008 (December) improved ‘wellbeing’ and walking, less pain, increased facial expression.
  • 2009 (January) Stronger and more alert, sleeping better
  • 2009 (February) More alert and confident, resumed serious mountain biking on steep, rough ground, reduced ‘off’ time.
  • 2009 (April) Resumed tuning and playing stringed instruments (after a gap of many years) improved fine motor control evident
  • 2009 (June) Mountain biking up to two hours, reduced dose of Sinemet by 8%
  • 2010 (September) resumed playing tennis regularly
  • 2010 (November) getting good sleep, tennis 3x per week, biking every day, playing guitar and accordion
  • 2011 (February) Entertaining 30 people at club, cycling, exercising daily, reduced Sinemet dose further
  • 2011 (April) Tennis three sets three times a week, offering music tuition on stringed instruments, daily cycling and running.
  • 2011 (October) Continues in good health as above
  • 2013 (April) Continues in good health and still active. No longer needs PIP but will return to it if any decline noticed.
  • 2014 (November) Resumed PIPmix but still playing tennis regularly

Summarised by Andrew Carmichael from case notes

Thank You

A gentleman who was diagnosed with Parkinson’s in December 2013 started on PIPmix in May 2014. Six weeks later this was his message:

I have spent the last week and a half in the North Lakes, we are regular visitors as we both enjoy fell walking not to mention our dogs :). We were last here in April, the most I could achieve without a short rest was 300 metres, inclines were extremely painful in the lower back and left leg.

During this stay we have walked most days on alternate days we pushed the boundaries 3 miles then 5 miles culminating in yesterday over 7 miles and 20,000+ steps in 4.5 hours, if I am honest only two miles today as a little sore in places but that’s to be expected 🙂 . I can’t tell you how unbelievable I feel thinking my days of fell walking were over to have enjoyed this break so much, could it be magic or PIP?

We return home on Tuesday if you would be kind enough to post out my next scrumptious jar please I would be grateful.

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