As research into the utilisation of carnitine grows, more known actions within the body are revealed. Primarily it is the essential co-factor in the transfer of long chain fatty acids across the inner mitochondrial membrane in type 1 muscle.Inability for this to occur results in lipid myopathy as is found in muscle biopsies of both genetic carnitine deficiency and post polio.3,4Acyl-Coenzyme A (Acyl-Co A) synthesis by carnitine is assisted by carnitine palmitoyl-transferase 1 & 2 enzymes and acyl-carnitine translocase(ACT).
Carnitine acts as an acyl sink to maintain adequate cellular levels of free Co-A.Carnitine also has a supportive effect on the immune system and in the maturation of the surficant of the lung lining.
PILOT STUDY RESULTS
The initial pilot study results established:
1.-
that appropriate levels of carnitine supplement-ation did in fact benefit
people experiencing the late effects of polio.Required
dosage may vary from 250mg - 3000mg.
3. -
that extra may be required above usual dose if greater that usual physical
activity was attempted.eg physiotherapy
session, sporting activities, shopping or other strenuous outings (best
taken prior to activity).
4. -
that cessation of supplementation eventually results in return of symptoms
(anywhere from 2 days to several months) and that resumption after a period
of previous stability then cessation may result in a permanent increase
in dosage requirements.
5.-
that it is possible that progeny of polio survivors may present with a
secondary carnitine deficiency.
6.-
that a minority of polio people did not appear to benefit from supplementation
(usually where more muscle wastage from polio and greater disability).
PRESENT STUDY Following the pilot study, serum
levels, initially undertaken as part of a double blind trial, were continued
as an investigative procedure prior to commencing new patients on supplementation
and as a means of confirming appropriate dosage.Serum
levels in WA are processed at PMH (Princess Margaret Children's Hospital)
The double blind trial revealed that
after a period of 4 weeks on a placebo, deterioration time on ceasing carnitine
varied from 2 days to several months depending on the individual and that
even after a month back on supplementation at the same dose, serum levels
were still inadequate and deficiency symptoms did not resolve until a higher
dose was taken.Several participants
experienced problems such as pinched nerve and mobility deterioration that
may be attributable to lessened support muscle function thus leading to
permanent further disability.The
trial was therefore discontinued on people already benefiting from carnitine
supplementation.
SERUM LEVEL RESULTS
When determining carnitine levels,
2 readings are given - free and total.Free
carnitine is the pool available to draw from.Total
carnitine includes free and acyl- (used or in use) carnitine.The
difference between the 2 readings is the acyl-carnitine level; ie carnitine
in use either as a long or short chain fatty acid combined with carnitine.Acyl-carnitine
is eventually excreted via the kidneys. see diagram on previous page.Other
carnitine studies also show that there is a significance in determining
the acyl/free ratio (N = < 0.4) and acyl/total percentage.
Varying levels are given as normal
depending on the carnitine research study.PMH
normals are free carnitine 30-60 umol/L, total carnitine 35-65 umol/L.
There are no other research results
available for carnitine in Post Polio except Dr Lehmann's brief Swiss Study
on 27 patients 1991-1993.Dr Tesch
in Berlin had a polio/carnitine study in progress but the results were
inconclusive.So for the purpose
of this study the following levels were taken as normal.
for polio - free carn>
45 female> 50 male acyl/total %10%-25% OBSERVATIONS
There appears to be a need for differing
levels of free carnitine in male and female polio people.(Other
carnitine research shows that males require a slightly higher level as
carnitine is used in sperm quality and motility.)
The observations of symptomatic
improvement by participants would suggest that for female polios a free
carnitine level of at least 45 umol/L is necessary.Male
polios appear to need to be at least 50 umol/L or even more.
Free and acyl/total percentage were
used as the main indicators of status as they appear to encompass availability
and usage.Free carnitine is presumed
to demonstrate amount available for future use.Adequate
reserves appear necessary to enable a tidal volume.Acyl/total
percentage is presumed to indicate amount in use at present, either as
usable or used portions.Other carnitine
research indicates that too great a percentage of acyl to total leaves
inadequate free reserves available ie over 50%, which could have potentially
serious consequences.(One study
shows death of a child with 50% ratio as possible cause of death.)Too
low a percentage would indicate too little being used.The
aim of this trial is to get a percentage value of around midway
ie 17% - 18% and free levels above
45 - 50.
CARNITINE READINGS A sample of 13 male and 14 female
participants have been graphed (see next page) to show common initial unsupplemented
free carnitine levels with each individual's reading paired to a second
higher reading when on supplementation and at which they have reported
subsequent improvement in symptoms; particularly, of fatigue, muscle pain
and endurance.Other improvements
commonly reported include improved sleep and reduction in brain fog.
It can be seen that nearly all initial
readings are in the lower half of normal or below normal and that the graphs
showing corresponding percentage reading for the same participants, usually
come up or descend to a better mid-range percentage.Where
this is not so, a further change in dosage usually achieves this.
Further charts below show pre-carnitine
and on-carnitine free levels for male and female participants.Readings
are sorted on age basis with youngest first.As
levels are undertaken as part of clinical assistance provided, it has been
difficult to get people to have further tests, particularly when they feel
better, get on with their lives and see no necessity to return to the clinic.
Invariably, most people have taken
themselves off carnitine and other supplements at some stage.Most
find that, eventual return of symptoms, prompts them to return to supplementation.People
are encouraged to include more red meat and/or avocado in their daily diet.Some
can notice the effects of stopping carnitine within a day or so.Others
may take a number of weeks to get back to previous low level symptoms.
The best way found to determine dose,
is to start with 250mg daily and increase by 250mg every 3 days until diarrhoea
is reached (overload), then reducing by the last 250mg will give dose point
for the individual.This is confirmed
if possible with serum levels.
The dose required by each person
varies and there doesn't appear at present to be any other indicator as
to how to determine appropriate dose for each individual.Some
people get by on 250mg - 500mg
Others may need up to 2,500mg.All
have found it better to take the whole dose all together before breakfast
for best effect.A few who have delayed
until lunch time, have found it reflected in lower serum levels and do
not get the boost an early morning dose gives.Taken
at night, sleep is usually disturbed due to excess energy.
Participants are encouraged to experiment
and feed information back.If after
taking normal dose, extra activity is undertaken or anticipated later in
the day, an extra 250mg gives another boost to meet increased activity
without fatigue and/or pain.
eg playing golf, shopping day, physio
session etc.
BLOOD GROUPS
It has been noted that blood types
A1 seem to have higher initial serum levels and don't seem to require as
high a dose to get benefit.Types
O and A2 are often lower and may require more supplementation.Other
work engaged upon by the Clinic, looking at diet in relation to blood groups,
indicate that A1 is suited to a more vegetarian style diet and may have
a greater dominance of type 2 muscles.Types
O and A2, particularly seem to do better on a red meat and root vegetable
diet and may have more Type 1 muscles.In
general, eating for blood types, ie O & AB (hot) and A & B (cold)
climate foods, appears to improve general health status. 17, 18, 19 A number of WA polios can relate
deterioration in polio status to coincide with less red meat consum-ption.In
particular, those of O or A2 blood groups, who endeavour to become semi
vegetarian, report rapid deterioration over 1-2 years and subsequent improvement
again on carnitine supplementation and resumption of a carnivorous diet.
PREGNANCY - CHILDREN of POLIOS
Enquires from participants about
the health concerns of offspring from birth to middle age resulted in consideration
of levels and supplementation for progeny as well.See
60 “children” with low levels.
Others have presented with a history
of lethargy in children, often in subsequent siblings, although some families
eg 4 under 6 years now, have all but first child with low levels.Improvement
is noted with supplementation usually in the 250 - 1000mg range.Other
progeny presenting to trial carnitine have been aged 2 - 63, may have a
history of poor athletic ability at school, always fatigued and worse in
pregnancy where female.One 6 year
old grandchild on carnitine has had comment from teachers of improvement
in school work and is now joining other schoolmates for playtime activities.
It would appear there is greater
risk to progeny where parents were experiencing deterioration at time of
conception of children.Levels of
increasing numbers of children of polio survivors are showing that often
they record lower levels than the polio parent, who is low.Where
there are grandchildren these may be lower again.A
recent surprise was the daughter of a polio who has 7 year-old twins.Mother
and one son always tired.Their levels
were below normal but other twin was normal.It
would appear one twin got more carnitine during develop-ment to the detriment
of the mother and other twin.
Carnitine supplementation during
pregnancy has made a difference to quite number of daughters of polios
over the last few years in WA.Most
report extreme fatigue and morning sickness which corresponds with their
extremely low carnitine levels.Where
polio survivors themselves are still having children there is often some
abnormality and delayed milestones.Secondary
carnitine deficiency can be triggered later.Trigger
factors, similarly to genetic carnitine trigger factors, include, vaccination,
severe illness, exhaustion, insufficient dietary carnitine, pregnancy,
fractures, surgery, fasting.These
same trigger factors have been noticed to precipitate PPS.
DIABETES CONCERN
It has been noted that quite a number
of WA members are reporting late onset diabetes.Some
report pre-diabetic symptoms of thirst, hypoglyc-aemia, craving carbohydrate
foods, mushrooms (high source of chromium - required for glucagon production).Subsequent
diabetes has been observed in one member who appeared to have low chromium
levels and a requirement for supplemental carnitine.As
she was a disabled pensioner and the cost of supplements not financially
viable, she did not continue and 12 months later was diagnosed as diabetic
by her GP.Others, supplemented with
carnitine (long term) and chromium (short term only) show improvement and
apparent resolution of pre-diabetic state where GP has been concerned about
glucose tolerance levels.
It would appear that Type 1 muscles,
although designed to utilise carnitine and fatty acids as fuel of choice,
can substitute glycogen if necessary.However
greater quantities of carbohydrates are required for same energy production
as protein fuel.eg via Krebs Cycle
- 36 ATP using glucose/insulin cycle compared to 129 ATP with fatty acid/carnitine
cycle.It is suggested that if carnitine
insufficiency occurs over a prolonged period, pancreatic exhaustion may
occur leading ultimately to diabetes.Other
carnitine research does report that carnitine supplementation stabilises
diabetic levels.We will be assessing
glucose tolerance, insulin levels, chromium levels etc in at risk polio
patients as part of our carnitine research over the next few years.
CHRONIC FATIGUE
The carnitine levels of 10 non polio
chronic fatigue sufferers have been surveyed in conjunction with this trial
and although their levels are usually low with low percentages too, the
level of improvement on supplementation is not as successful as with polios.Several
carnitine studies have been done already looking at chronic fatigue.6 GENETIC CARNITINE DEFICIENCY
As this is a reasonably rare condition,
participants are hard to find.Two
families with suspected carnitine deficiency that have had levels done
would suggest that in some instances with this condition, before carnitine
readings, are initially high ie free carnitine above 60 umol/L and on appropriate
supplementation of 2-3 Gm the levels reduce to below 60 with a corresponding
improvement of symptoms and no signs of overdose.It
is surmised that by increasing the available pool of carnitine, more is
able to filter through to the muscle, so lowering serum levels.Thus
a totally different serum picture is shown to that of post polio.
QUALITY of CARNITINE
There have been some concerns on
the quality of carnitine available.Carnitine
can be observed to be pure powder or to have a crystalline (sparkling)
consistency.Participants report
problems from crystalline carnitine (ie ineffective, need to double dose,
rash).This seems to be particularly
so where general health is not good as in post polio, CFS.
The manufacturing process for carnitine
in the last few years, has now cut out the final stage that reduced crystalline
to powder but we have found that a further grinding process tried in desperation
by our pharmacist supplier, restores it to powder with beneficial results.Participants,
unaware we had been having problems with quality, have rung in to say that
their last lot (powder) was working better than the previous bottle.
OTHER SUPPLEMENTS
There seems to be a correlation between
B6 availability/levels and carnitine in particular, and also with magnesium.These
are the most common extra supplements required by polio survivors.B6
has been found to be effective on nerve pain ie sharp electric shock pain
or pins and needles.Magnesium is
a natural muscle relaxant.Other
items commonly required are glutamine, (neurotransmission in the brain
and also required in muscle function when exhaustion levels reached) and
choline (which is instrumental in acetylcholine production (the neurotransmitter
for muscles).
Where weakness is occurring there
seems to be a need, particularly in those with more damage from polio,
for nerve support.This is being
achieved with appropriate doses of B6, choline and glutamine.B12
may also be required.Low B12 levels
allows greater excretion of carnitine as shown by Dr Vogelaar, a clinical
biochemist, visiting WA from Holland.
CARNITINE and BETABLOCKERS
An interesting study found on Medline
may explain why polio survivors have problems with some hypertensive drugs,
beta-blockers in particular.20 It was observed that in a study of
dogs with heart failure, beta-blockers decreased carnitine palmitoyl transferase
1 enzyme, essential for facilitating the progress of acyl carnitine through
the mitochondrial membrane.If, as
the WA study shows, carnitine levels are already low in polio survivors,
the addition of beta-blockers would further jeopardise carnitine utilisation
in the body, thereby explaining the international alert on beta-blockers
in post polio.
The article concludes "Metoprolol
(Betaloc) induced a decrease in CPT-1 activity and an increase in triglyceride
content.These results suggest that
the improved function observed with beta-blockers in heart failure could
be due, in part, to a decrease in CPT-1 activity and less fatty acid oxidation
by the heart." 20 Yet another Medline study shows significantly
improved exercise tolerance of patients with effort angina, concluding
"these
results indicate that L-carnitine is a useful therapeutic agent for the
treat-ment of congestive heart failure in combination with traditional
pharmacological therapy." Japan Circ 1992 56(1)
It has been noted amongst WA carnitine
users that the inexplicable chest pain often encountered in post polio
and attributed to muscle spasm as ECG is normal, disappears when on carnitine.
Many post polio difficulties appear
to be linked to a metabolic problem caused ultimately by decline in general
health and exacerbated by muscle type change due to the recovery process
after polio.
CARNITINE SPARING
Lately attention has been drawn to
the effects of improved liver function on supplemental carnitine requirements.A
trial on supplementation of the amino acid, taurine, over the last 18 months
has shown the benefit of 500mg of taurine daily.
This has slowly been effective on
the liver, allowing ultimate dose reduction of carnitine and also B6 and
Vitamin A requirements.
A further trial has started in 1999
to look into the effectiveness of a Sunflower Oil (detox and immune stimulation)
morning mouth rinse "An Explanation of the Unconventional Healing Process
within the Human Body by Sunflower Oil." published in "Australasian
Health and Healing "Vol 15 No 1;
Nov 95-Jan 96 attributed to a Dr
Karach.Initial participants have
reported a further reduction in carnitine dose requirements and other supplements.
CONCLUSIONS
A lot more work needs to be done
in this area before firm conclusions can be reached as to the reason for
low levels in post polio people.Not
withstanding, carnitine supplementation is a safe, easily available, though
reasonably expensive, adjunct to present treatment options for PPS.
The WA Polio Clinic is essentially
a small preliminary assessment and referral clinic staffed by a registered
nurse with a supervising honorary doctor (polio survivor).There
is no funding for research and the study outlined here has been developed
from clinical attempts to improve the symptomology of patients attending
the clinic seeking help.Success
must also be attributed to patient feedback.It
has been a partnership program.
Some very interesting results and
observations on utilising carnitine to best advantage, have been made by
participants.The WA Polio Clinic
is looking at a number of areas in an effort to assist with individual
problems presented by polio survivors.
The symptoms of PPS appear to be
tied to a deterioration in general health status that has a cascade effect.Polio
survivors seem to have less leeway than other members of our community
before running into problems.As
certain vitamins and minerals seem to be also tied into protein metabolism
as is carnitine, a lot of other minor problems indirectly associated with
post polio, can be resolved by correcting vitamin and mineral imbalances.For
example tight muscle problems like cramps, spasm, backache, headache, respond
well to an appropriate dose of a magnesium supplement, a safer alternative
to valium in post polios.
The Polio Clinic has four further
studies under way.
1Emu
Oil as an alternative to cholesterol reducing drugs - which can increase
muscle deterioration in post polios.
2Supplemental
boron to assist with arthritic type problems, common with overuse in post
polios.
3
Gelatine supplementation for joint problems is showing success.Gelatine
is the precursor for cartilage formation (Type 2 collagen) and has all
but disappeared from our normal diet.
4 Creatine
as an adjunct to relieving fatigue and increasing stamina.
The object of this paper is to stimulate
further research that is beyond the capacity of this small clinic, by other
Polio Clinics and researchers.It
is hoped that in the near future supportive evidence by other similar studies
to the WA study will emerge from other parts of the world.
REFERENCES
1.
Borum P. 'Carnitine' Dept
Biochemistry VanderbiltSchool of
Medicine Tennesseepp 233-257 2.
Carter A et al'Biosynthesis and
Metabolism of Carnitine'J Child
Neurology 1995; 10 (Suppl) 2S3-2S7 3.
Gilbert E.'Carnitine Deficiency'Dept
Pathology /Lab Med Wisconsin Uni.Pathology
1985 17pp161-169 4.
Halstead LS Grimby G (eds) Post Polio Syndrome.Philadelphia:
Hanley & Belfus Inc 1995 5.
Shils et al‘Modern Nutrition
in Health & Disease’Baltimore:
Williams & Wilkins1999 6.
Kuratsune H, et al.Acylcarnitine
Deficiency in Chronic Fatigue SyndromeClinical
Infectious Diseases 1994:18 (Suppl 1) S62-67 7.
Lehmann T C.'L-Carnitine and
Post Polio Syndrome'1994Dept
Ventilators & Post Polio Bern Switzerland 8.
Martini F.Fundamentals of Anatomy
and PhysiologyNew Jersey.Prentice
Hall Inc 1989. 9.Moffett
D, Moffett S, Schauf C.Human
Physiology St Louis Missouri.
Mosby1993 2nd Edition 10.
Murray MT.' Carnitine'.In:Encylopaedia
of Nutritional Supplements - The Essential Guide for Improving Health
Naturally.California: Prima
Printing 1996: 283-295 11.
Pons R , de Vivo D'Primary and Secondary
Carnitine Deficiency Syndromes'J
Child Neurology 1995; 10 (Suppl) 2S8-2S24 12.
Rebouche CJ, Engel AG, ' Carnitine Metabolism and Deficiency Syndromes'Mayo
Clinic Proc 1983: 58: 533-540 13.
Schater M, Medoff G, Schlessinger D (eds) Mechanisms of Microbial Disease.Baltimore:
Williams & Wilkins1989 14
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Harrisons 1999 15.
Trojan DA, Cashman NR.Current
Trends in Post Polio Syndrome.Montreal:
Milestone Medical Communications 1996 16.
Williams S R,'Nutrition and Diet
Therapy'St Louis, Missouri:
Times Mirror/Mosby College Publishing1989. 17.D'Adamo
P, 'Eat Right 4 Your Type' New YorkUSA
Putmans 1996 18.
Jupp T, Foster B, 'Is Your Blood Group Written on Your Face?' PPNWA
booklet 1995 19.
Jupp T, 'Balance by Blood Groups' PPNWA booklet 1998 20.
Panchal A et al 'Beta-receptor blockade decreases carnitine palmitoyl-transferase
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Card Fail 1998
June; 4 (2):121-6
DOSE
One
member, having her first child at 37, had been faring poorly through her
pregnancy when she attended the Polio Clinic in June 1997.Her
carnitine levels at 21 weeks were found to be free 16, total 17 and 6%.(Other
carnitine research has observed that carnitine levels halve by 16 weeks
gestation. ) On 1.25 G of carnitine her levels were 36 and 50 and 24%.Her
vomiting ceased and energy levels returned.We’ve
had other similar pregnancy stories.