Is there a place for Lithium to reverse or control neurological damage induced by chemotherapy?

The buried, older literature on Lithium continues to amaze me, published in a vast array of peer-reviewed papers.  There seems to be little interaction of the medical community in applying its uses.

One of the most frustrating pains is that of post-chemotherapy neuritis especially of the lower legs.  This pain is extremely distressing as a mixture of sensory disturbances – burning, hypersensitivity, pain etc. together with at times of “epileptic bursts” of pain in the feet.  This is extremely distressing to patients as it seems to occur or is more noticed when attempting to sleep.  The use of the standard AEDs such as Lyrica, Neurontin, and Cymbalta in my experience is of limited use in severe cases.

Many cases of post-chemotherapy neuritis come on after many years, often decades.

One of the most useful treatments is the topical application of 5,10 or 15% Phenytoin in a variety of bases often of a liposomal nature.  This work has been spearheaded and raised to a level of “go to” treatment by a double-blind study by Professor Jan Hesselink.  Time will only tell how well this treatment is accepted.  The main form of topical Phenytoin is patented in Europe.  From my limited use of this product, it is of an outstanding value with continuing effect which may increase with time and break the pain cycle.

In many ways, this article was going to end at this point however readers of the various articles of mine will appreciate that Lithium has a high standing in my present view of medical problems ranging from Alzheimer’s, depression, anxiety, not to mention the potential of cell regeneration in many neurological conditions.

As far as I am aware, Lithium has not been used in the treatment of latent, over 1 or 2 decades, of post-chemotherapy neuritis.  Thus, it was with considerable interest that I read the paper by Petrini “Is Lithium able to reverse neurological damage by vinca alkaloids”.  This was an interestingly crafted paper administering Lithium in the form of carbonate to both humans and mice and measuring the neurotoxicity as in neuropathy.  Both humans and mice showed a marked improvement or abolition of neuropathic toxicity from chemotherapy.  All the human patients started Lithium after they developed symptoms of neurotoxicity.  One wonders if Lithium was given closely associated with the chemotherapy if this would have been avoided? In conclusion to their paper, “both results from animal experiments and human observation show that Lithium administered may counteract the acute or semi-acute neurotoxicity of vinca alkaloids”.  There seems to have been no effect on the decrease in chemotherapy effect on the myeloid disorders that they were treating.

The big question and the study that needs to be done especially since Lithium in the doses that were used cause no concern, the equivalent of 600 mg of carbonate, is should this be used as a routine in a series of patients receiving chemotherapy?  This seems to be no antagonism of Lithium to the chemotherapy.  This paper was mainly concerned with the semi-acute neuropathies but I think a long-term study would be rewarding and needs to be completed.  It seems that the Lithium effect from the past work of this group does not affect the inhibition of the chemotherapy agents on their lymphoid tissue targets.

The simple question to be asked is, is there a place for Lithium during chemotherapy?  I can see little downside!

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In the beginning, Lithium!

Having nearly exhausted the extensive modern work on micro-lithium (as compared to high doses used for bipolar disease) I thought it would be interesting to look at historical facts.  Part of this is that I have lost faith in the gold standard double-blind study.  This seems to be only as good as the questions asked, the study design, for those that carry it out and the various analyses and indices that measure its success.  A great deal was taught years ago on the history of the development of drugs before it was superseded by the rather leaded feet of a double-blind study.

With Lithium, and especially the research carried out by epidemiological studies in Texas one would obviously focus on mineral wells in Texas.  James Alvis Lynch was a small ranch owner in Texas.  In 1877, he decided to find new pasture for his herd.  James and his wife suffered from rheumatism.  Rumours of a Comanche attack made them decide to move to a northern part of Texas.  The land they “purchased” in 1888 had one disadvantage, there was no fresh water for 4 miles.  The first well they drilled on the proper yielded water with “a funny taste” however it didn’t seem to affect the livestock and so it became the source of their drinking water.  It was interesting to note that after a few weeks, their arthritis seemed to improve, the area they settled in did have a drier climate but the results of climate on rheumatism is not proven.

The word of their arthritic response to the well water spread quite widely and strangers came from all over the state to drink and purchase the water.  The original well produced 100 gallons per day and this was soon found to be insufficient.  Based on this response, the town of Mineral Wells was laid out in the fall.

Of the various wells drilled, some seemed to be more therapeutic than others and later on the water was tested and found to contain significant amounts of Lithium.  The therapeutic healing effects of the water in Mineral Wells brought tourists from many areas not to mention many companies setting up to bottle the healing water.  To reduce the cost of transportation, the water was evaporated and the crystals (composed of Lithium) could be added to your tap water.  Bottled water production from Mineral Wells declined for a number of reasons – the Depression, new rules from the FDA, and the advance of the so-called wonder drug pills.  At the time of writing this brief note, one company still sells the famous “mineral water”.

It is hoped to be able to find the concentration of Lithium in the water from the old literature and also the instance of rheumatic illnesses, mental illnesses, and the general health of the population.  This sounds like the perfect micro chasm to study although I imagine the town water has been purified.

When does the failure to investigate an agent of great human benefit become a crime?

For the past year, I have been very interested and focused on the micro uses of Lithium in a whole range of neurological conditions.  Perhaps one of the most interesting is the effect of criminality, covering a whole spectrum from murder, rape, robbery, drug addiction, suicide, and mental certification.  A friend wondered why it had not been followed up?  Perhaps even offering it to prisoners in jail?  From the literature, some prisoners may well be suffering from a lack of lithium.  I think it is a great idea!  Micro Lithium in water is at present on sale in many countries and a drinking fountain with Lithium in prison facilities would give prisoners access to micro doses of Lithium.

The work of Schrauzer and Shrestha dates back to a collection of data in the late 1980’s and this has been confirmed by a number of other studies showing a direct link between low intake of Lithium and violence, antisocial, or criminal behaviour.  Referring back to the graphs by these authors, one does see the very distinct association between low lithium in water supplies and the whole spectrum of criminality.

Considering that the above is correct, what a saving of suffering of life and death, could be achieved by making micro Lithium available.  At present micro Lithium is not included in vitamins or sold without a prescription (again Lithium that is available is in doses used for manic depression).

After reading the importance of Lithium in water as a source of adequate intake, I was considerably disturbed to discover that townships using Lake Ontario as a water source have only miniscule, undetectable by water board standards, of Lithium.  The level of Lithium in lake water (drinking water) in Toronto have been so low that continuation of measurement has been discontinued after a 10-year period of finding no detectable Lithium.

In the last few years, Lithium, has been determined to be an essential element with a dose far below that found in a number of spas – for example Baden Baden in Germany which has long been recognized for its health-giving waters.

This is not new as in September 12, 2014 distinguished psychiatrist Dr. Anna Fels wrote in the Sunday Review “Should we all take a bit of Lithium?”.  Similar articles have appeared in European papers.

What would it take for conventional, staid, public health to consider looking at the question of micro Lithium being available in multiple vitamins, tonic waters, and doses equivalent to the RDA (recommended daily allowance)?  The savings in suffering, controlling violence, etc. would be vast and would go a great deal to reduce our healthcare budget.

For those that still are confused between the doses of micro Lithium 1 mg and under and the 300 mg plus used for manic depression, should consider one being present in nature and the other used therapeutically at 300 times the dose.  At present, there is a solid wall against taking any significant micro Lithium doses excepting .1 per million.  Never before have we had the opportunity of changing social behaviour and the often-vicious side effects of this, not to mention cost etc. by such a simple agent.  Why is micro Lithium not added to vitamins?  It has been agreed that it is an essential element of which our intake is I believe, lower than ideal.    In a small study using hair analysis all cases had abnormally low Lithium.  This may not be ideal to the purists but having spent a considerable amount of time talking to a biochemical lab, levels other than those to monitor patients with bipolar disorders are not available for labs to investigate.

From previous articles on Lithium by this author, one would see the collective possible positive advantages of Lithium in many conditions that were thought to be untreatable.  This includes the effect on GSK-3, an enzyme that builds plaque, and an improvement on longevity – but still we ignore micro Lithium.  I suppose I should point out it also has a romantic effect!

For those that doubt the safety, I point out that until 1946, 7-UP contained Lithium.  The “7” actually stood for the atomic weight of Lithium.  I believe it was withdrawn at the request of public agitation for unaltered water.  Over the past decade there has been considerable public anger at the decreasing nutritional value of food due to poor or cheap fertilizers and overused land but little concerned has been expressed by our tap water being deficient in many areas of Lithium.

From my limited medical experience of micro Lithium, I think this is very much a win-win situation – medically and in social realms of human behaviour.  I think the effects on drug addiction may be related to this inner rage or lack of inner satisfaction which causes one to seek drugs which may be altered by a normal supply of micro Lithium. 

Isn’t an article being published in the “New York Times” almost as good as being published in a medical journal?

 

 

The puzzle of Lithium takes another step in being difficult to rationalize

The scientific work by Friedlich demonstrating neocortical levels of lithium are increased in bipolar disorders raises a number of questions. 

First, it establishes that Lithium is present in brain tissue as a physiological trace element and from other work an essential element in human nutrition.  This and other observations firmly establishes Lithium as essential and of major importance in neurological function.

This astounding and confusing feature that was found by the work of Friedlich et al that the cortical levels of Lithium are significantly elevated by a factor of two in the cortex of bipolar patients when compared to normal cerebral tissue in controlled patients.  Considerable care was taken that the bipolar patients had not been on Lithium treatment.

The real puzzle is finding significantly higher lithium in the cortex of patients with a predisposition of manic depression when the major treatment is to give lithium and thus raise the cerebral level for the treatment of manic depression.

A number of theories have been proposed but these are really not compatible with past problems noted in the body with other elements.  One idea proposed is that in patients with bipolar disorder there is a deficiency in “lithium transport pathways” and thus one obtains an excess of lithium.  This jars against normal physiological process but certainly warrants possible investigation into lithium pathways or abnormalities in inter-cerebral pathways and any differences between manic depressives and normal patients. 

It is a real question why one finds an accumulation of lithium in brains which would possibly respond to therapeutic doses of lithium for treatment.

It is interesting to note that “Happy water” is for sale in Canada which contains a miniscule amount of Lithium.

 Reference: Friedlich. Neocortical levels of lithium are increased in bipolar disorder.  Molecular Psychiatry 2012 17:3-4

The puzzle of Lithium

After the acceptance of Cade’s initial brilliant work on the effect of Lithium salts on bipolar diseases and the slow use of it in severe depression, Lithium has been in the doldrums of further investigation.  Under medical control it has found to be effective, safe, and toxicity has been well observed and controlled – this is in significant doses of 900-1200 mg per day with monitoring. 

Their research seems to have stopped with its use in bipolar disease and depression.  Little attention if any has been focused on a multitude of other disturbances of mood, degenerative diseases of the brain and spinal cord, personality effects, etc.  One would have thought that with Lithium having been shown to be effective on bipolar diseases (manic depressive illness) that there would have been a flurry of further investigations on other diseases of the nervous system.  But no, this seems to have been the end of the story!  Again, is it a result of no patent, no profit?  Where are the societies to put up the baton of Lithium research – missing I fear!  Profit seems to be the only motive for research in many subjects.

One is struck by the differences in nervous tissue particularly the brain than the rest of the human body.  Firstly, the brain is somewhat isolated by the blood-brain barrier which excludes certain elements, natural or otherwise, from affecting brain physiology.  Like the heart, the brain works 24 hours per day and both have end arteries where a blockage would cause infarction.  On review one is struck by the number of degenerative disorders that affect the brain compared to other tissues and organs in the body.  Interestingly, many of these degenerative disorders ranging from Alzheimer’s, Picks Disease, motor neuron disease, etc. are of unknown etiology for the most part, poorly understood regarding treatment etc.  One wonders whether these could represent a common response to a single entity?

Medicine is very poor dealing with degenerative illness yet Lithium has been shown to be effective in stimulating or regenerating neuronal cells in parts of the brain particularly the hippocampus and grey matter.  One is struck by the absence of studies on micro or medium doses of Lithium in these degenerative illnesses.

It is puzzling the hiatus from Cade’s work showing that Lithium was a good treatment for bipolar disorders and depression. 

Perhaps the real point of this discussion is that there is no one responsible for promoting natural agents.

There is considerable literature in small animal studies that Lithium may be useful in preventing degenerative disorders in the brain, opening the spectrum of help in Parkinson’s Disease, Huntington’s Disease, Alzheimer’s Disease etc.

It is puzzling that there is no definitive literature on Lithium intake related to degenerative disease in the brain or for that matter pure values.

 

Lithium in ground water

Some of the brief notes on Lithium are based on small animal studies however the science of Lithium levels in drinking water and the risk of abhorrent behaviour, suicide, aggression, crime rates are supported by a number of studies ranging from Texas, Japan, Italy, and the United Kingdom.

My own impression over the last few decades is that idiopathic suicide rates are increasing with devastating effects on families and social networks.  The reactionary suicide often associated with underlying depression can be understood.  But the idiopathic suicide of young people in good health is extremely puzzling as is the increased violent behaviour and “short fuse” syndrome.

The scientific studies mentioned above show an inverse relationship between Lithium in ground water and thus in drinking water and the abhorrent behaviour.  A number of leading articles have suggested placing Lithium in minute quantities equivalent to what is found in the ground water of many countries into the drinking water in those countries where it is deficient.  I realize the outcry about the use of Fluoride and can not comment but we accept chlorination of water without concern as it helps protects lives and prevents infection.  If Lithium was added to city water supply where the content is zero, I wonder whether we would see a change in the “short fuse” syndrome, aggression, crime as suggested by reviews on the effect of ground water on behaviour.

I really can not see this happening with the violent social network reaction and hysteria but certainly the publication of guidelines might help in the re-supply of bottled water with small amounts of Lithium.  It was interesting to note that 100 years ago spring water with small amounts of Lithium were best sellers as it has a calming effect, up to 1946 Lithium was added to 7Up so that they could get on the Lithium bandwagon.  It seems we are in a state of scientific decline.

I have often wondered why a few friends frequented certain spas like Baden Baden.  Was it for the relaxation, the social life, or was it for the 8 mg of Lithium per litre of spa water?

As mentioned in a previous article, the Romans were obviously aware of the value of alkali springs (containing Lithium) and suggested that soldiers suffering from, a poor translation from the Latin, post-traumatic syndrome or exhaustion should partake of the alkali, lithium containing waters!

 

 

Born without a manual or do we have one and don’t use it?

Perhaps one of the great inventions has been the iPod especially for someone like myself who’s eyes get tired from reading.  The iPod is a true marvel but it was the first complex entity with the smallest manual ever seen.  Somehow young people seem to have an inherent knowledge on how to use modern technology, I’m certain that in a few decades people will have a new speciality dealing with thumb wear out.

The greatest miracle of all is that of mankind, top of the animal and plant kingdom.  When puzzled by an illness or disability and pressured by the patient, I often fall back on “well you didn’t come with a manual that I can refer to and we are still learning about the human body and disease”.  I have used this defence so often that I am beginning to wonder whether there is a manual but we have not learnt how to look for it.

The manual to the human body might be hidden in the periodic table.  In the evolution of life whether it be by evolution or divine origin nothing is wasted, everything is honed to efficiency.  Inside a body hundred of thousands of enzymes function under automatic control, very occasionally with a genetic abnormality the enzyme system fails producing rare metabolic disorders.

Coming back to the idea that nothing in this universe is without purpose, perhaps the Periodic table hold the key?  A number of elements we now know are essential to life and in increased doses to illnesses.  What about the other elements which are somewhat ignored?  Do they have a place in treating illnesses that we do not understand?  At random I selected a range of elements including Vanadium, Arsenic, Selenium, Yttrium, Lithium and Strontium.  I was truly amazed at the interesting actions on various enzyme systems and positive effects of Vanadium, Selenium, and Strontium – the latter I often forget.  Strontium ranelate is cleared for sale in a number of countries to deal with Osteoporosis and bone fractures.  I’m certain many physicians are rather frustrated by the present medications, increased calcium intake on the effect on Osteoporosis for a reasonable cost.

In summary, is the Periodic table the index of agents some of which may have great potential in medical use?  Nature does not waste its time producing elements for the sake of it. 

Everything has a purpose but we are not looking carefully enough!