Are we blind to the link between Lithium and Alzheimer’s Disease?

It seems that this simple element blocks the function of GSK-3β.  It is interesting that elderly patients with manic depression treated with Lithium have a lower incidence of Alzheimer’s Disease compared to others not treated with Lithium.

The article by Wise Young “Review of Lithium effects on brain and blood” Cell Transplantation 2009 18:951-975 compelled me to write.

It is sad but interesting to note that attempts to treat Alzheimer’s with new pharmacological agents have been disappointing and one large multinational company has withdrawn from this field. 

It seems that the key is very early treatment, once the β-amyloids have formed it is like dealing with concrete whereas prevention of amyloids may be the answer.  This leads to the question of how can we diagnose Alzheimer’s early?  As pointed out earlier this may be due to early neurological abnormalities in nerve fibres detected by photograph enhanced retinal fibre changes.  Both of these avenues are easy to undertake and may offer hope in this crippling illness.

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Is this a micro-Lithium plot?

As readers to my articles would glean, I am a fan of micro-Lithium at its recommended daily dose.

·         It is established now that Lithium is an essential mineral

·         Intake in many countries is reduced due to water sources being Lithium deficient from lakes, rain reservoirs etc.  The water from Lake Ontario has no detectable amounts of Lithium for the past 10 years.  This lack of Lithium in the water is aggravated by the addiction to bottled water.

·         Micro-Lithium can not be bought or found in any over the counter preparations

·         In the past Amazon and other USA sales outlet would export micro-Lithium to Canada.  Recently, this small importation was blocked by Health Canada together with L-Tryptophan another favourite agent in my thoughts.

·         I am grateful for the search by the Natural & Non-prescription Health Products directorate that found “our database indicated there are no over-the-counter (OTC) products containing Lithium.  All productions containing Lithium are under prescription status”.

·         Adding to the submersion of Lithium, is the fact that I have been unable to find a laboratory that is able to detect micro-levels of Lithium in blood (routine tests for micro-levels for bipolar disorder is readily available and insured under OHIP).  The few hair analyses I have carried out show significantly low levels of Lithium in patients on a good diet!

·         This blockade on Lithium continues and is somewhat unique as one looks at the micronutrients in multiple vitamins available in Canada or those shipped from the USA, lithium is absent.

·         In spa areas which are famous like Mineral Springs in Texas and Baden Baden in Germany, the levels are in excess of the RDA intake.

·         With the spectrum of actions that have been documented from memory, dementia, cardiovascular, love, drug addiction, crime, etc. it is quite amazing.  One universal action of Lithium is in reducing the “short fuse syndrome” it would be great as option in drinking fountains in prisons.

I’m certain that many readers are fed up with the Lithium beating of the drum, but this recent tirade was stimulated by finding that the Lithuanian study on Lithium in ground water and suicide confirmed many of the findings of the studies in Texas.  If Lithuania with its small population can carry out this research, I wonder why Canada lags behind?

 

Lessons to be learnt from Lithium

The paper Lithium: the pharmacodynamic actions of this amazing ion by Kayleigh M. Brown in Therapeutic Advances in Psychopharmacology 2013; 3(3):163 raises a number of interesting points.  Perhaps the most important is the fact that Lithium works by inhibiting enzymes, with the most important being GSK-3.

At the same time, I have been catching up on my reading on the actions of tranquilizers, anti-depressants, mood modifiers, etc. and was struck by the main method of these and many other drugs like hypotensive etc. is on receptors.  It seems that many cells in many conditions having one or more receptors blocked spontaneously produce more receptors and thus weaken the action of the drug.  On reducing the dosage of the active drug, one gets a reverse effect.  In the sense that there are a large number of active receptors without an agonist thus withdrawal might produce more symptoms than prior to treatment.

I think the above idea that cells respond to the blockade of receptors by producing more receptors is a worrying problem particularly with anti-depressants, tranquilizers, mood-modifying drugs etc.   Withdrawal can cause more symptoms than the original illness.  Lithium seems to work by enzyme inhibition.  Luckily, inhibition of an enzyme does not seem to produce more enzymes and consequently flooding the blockage.  Thus, we have GSK-3 and inositol monophosphates enzymes that control many functions that can actually be blocked without producing a by-pass effect. 

It seems that GSK-3 particularly has a vast array of actions, blockade with Lithium ion seems to have many positive effects.

Like two faces of Eve, Lithium has an effect in large doses on manic depression and micro-doses (1 mg or less) have an effect on many other agents.  Micro-dose levels such as are found in drinking water in many areas and has been associated with a reduction of dementia, violence, crimes, etc.  Perhaps, the effect of Lithium in water is to reduce addiction and we seem to be full-speed ahead for filtered, reservoir water and we are all going to suffer from Lithium deficiency!

Actions of micro-Lithium:

·         Longevity

·         Treatment and prevention of dementia

·         Memory

·         Ischemic heart disease and hypertension (this has been known since the last 1900’s that hard water reduces heart attacks and hypertension!)

·         Spread of strokes

·         Anti-drug addiction

·         Love, sex, emotion

·         Neurodegenerative illnesses which seem to be promoted by the activation of GSK-3

·         Reduction in short fuse syndrome – over the past few decades, reaction to often minor annoyances result in violence thus short fuse syndrome is increasing

·         Shown to be effective in preventing the degradation of cartilage in the prevention of Osteoarthritis!

An interesting study would be on the use of Lithium in prisons where it has great potential to reduce the build up of violence and anger.  The introduction of a fountain with water containing Lithium is all that is needed.

From self observation, Lithium produces a minor tranquility but no effect on reaction time, a marked increase in memory recall, reduction of short fuse syndrome, not to mention a reduction in hypertension.

There are many things wrong with this world that was perhaps designed as a near perfect planet.  The removal of Lithium in our diet or water has based on many papers from Texas, Japan, and Lithuania has been associated with increased suicide, drug addiction, crime, etc. yet we continue on this path.  Never has such a simple answer to our problems been available – Lithium!

What more can you expect from a treatment costing less than $100 per year!

 

2 arms of Lithium research merge into near positive proof

As pointed out previously there has been considerable scientific literature that micro-doses of Lithium have a significant clinical effect.  This ranges from epidemiological studies of ground water Lithium to small oral doses that affect higher cerebral functions including cognitive and emotional.

The recent paper by Vanessa J. De-Paula in Bipolar Disorders 2016; 18:692-95 provides perhaps the most important step in appreciating micro-Lithium.  Her studies using cell cultures of cortical and hippocampal neurons demonstrated that low doses of Lithium 0.02 and 0.2 mM increased brain-derived neurotropic factor (BDNF).  The latter is an important factor in a whole range of neuronal function particularly its protective response in preventing degenerative cell changes and the resulting functional disability.

The results demonstrated that micro-Lithium concentrations produced highly significant improvement in BDNF secretion.  Just as interesting was the less improvement in intra-cellular BDNF in the higher dose of 2 mM concentration.  This is equivalent to the concentration of Lithium found in patients with bipolar disorder.  Little is better than more for the improvement in cortical function.

Many faces of Lithium

Over the past year I feel that I have covered a wide spectrum of proven actions of Lithium from improvement in cognitive function, reduction of violent crime, drug addiction, suicide, etc.  It was only in looking for abnormal side-effects of micro-dose Lithium that I came across considerable work clearly demonstrating a correlation between hardness in water and atherosclerotic heart disease (Voors et al Am J Epid 1970;92:164-171 and 93:259-266).  Of the six elements in drinking water causing hardness the best correlation of improving AHD is that of the Lithium content.  It is interesting that the literature in this era has Lithium in drinking water.

With the cost of ischemic heart disease (IHD) I would have thought that the article in The Lancet December 20, 1969 “Does Lithium depletion cause atherosclerotic heart disease” would have been followed even at this late date.  From the article, “it would entail a highly cost-effective means of preventing AHD and improving the quality of middle-aged life through simply enrichment of municipal water supply”.  It draws attention to the action of Lithium antagonizing five of the most potent AHD risk factors – hypertension, diabetes, tissue uric acid, type A behaviour, and serum lipid levels.  See posts on Garrod discussing lithium and gout.

Concern with tampering of water supplies is understandable but just raises the Lithium concentration in communities drawing the water from lakes, rivers, or reservoirs to that found in many countries where there is no obvious evidence of toxicity in their Lithium levels might be justifiable or warrant more research.

I suppose it is never too late to learn!

 

A Lithium study of one

Years ago, I would have been very apprehensive of writing about this brief period of observation on the use of Lithium.  I was brought up in medicine to have great faith in the double-blind study, this was reinforced by meta-analysis which analyzed other people’s studies and applied complicated statistical formulas.  As we have seen over the last few years, this system is flawed and studies on statins, cholesterol, calcium, and anti-depressants have proven to have feet of claw and the results have been erroneous in some cases.  This excludes the fact that some studies have been faked.  It is estimated that perhaps 50% of patients on hypertensive medication could be weaned off as blood pressure can reset itself.  I really can not imagine such a study being funded so people continue to take the medication which they may not need.

For the last couple of years, I have tried to interest organizations to carry out a double-blind study on Lithium.  It suffers from a number of problems preventing financial support.  There is a great deal of confusion between Lithium used for manic depression and in a totally different field the micro amounts of 1 mg per day, the recommended daily allowance (RDA) that we are talking that interests me.  Another negative factor in Lithium studies is that it has no patent, no profitability, is extremely cheap, and natural.  Having followed the academic literature for half of a century, I can think of very few other agents that have such a wide spectrum of scientific evidence of its uses but to nail its total acceptance there needs to be a double-blind study and there is no financing for this.

Years ago, I became extremely involved in the Glucosamine story and self-funded a study in Toronto which proved positive but poorly funding the study was not outstanding.  Money is the key ingredient for funding a study.

With the above in mind and the fact that I would only be taking half of the RDA of Lithium, I started taking 0.4 mg of Lithium in water per day.  Being unable to determine a blood Lithium level through the usual channels, I found a hair analysis that was accurate to my profile which showed my Lithium level to be way below the accepted normal value. Prior to starting Lithium  basic routine blood work was carried out including creatinine.

For the first 6 weeks of daily micro-Lithium I noticed no obvious change in memory, behavior, or any effect at all.  This was rather disappointing but in retrospect Lithium is a slow working agent in micro doses, working on a physiological level rather than a therapeutic level.

The first positive effect which surprised me was it stopped a short fuse reaction or minor anger.  Many things these days are very frustrating from the answering machine, to driving where red lights are run through.  As a physician, one has to bottle up our annoyance; I found on the dose of Lithium I was much more tranquil, less sensitive to irritation, and particularly to patients who do not appreciate the problems in health care.  This has made a very significant difference and has a number of positive sequelae.  Perhaps most interesting is a reduction in my blood pressure, needing far less medication.

I suppose we should put in the fact that I have no financial or conflict in promoting Lithium other than the good I think it does.  Also, this is not giving medical advice but an attempt to draw attention to Lithium.  The observations on anger and short fuse syndrome are supported by a number of studies from Texas to Japan to Lithuania.  Many problems today are due to a short fuse reaction whether it be driving, social relationships, or suicide.

I have one addiction other than work and that is chocolate, it gives me energy, sharpness, and satisfies a craving.  After a bar of chocolate eaten in 30 seconds my work level improves!  Sugar, caffeine, and cocoa! Since being on the daily routine of Lithium, I still enjoy chocolate but I don’t have the craving for excessive consumption.  These observations just appeared, I had no idea what I was looking for so it removes the bias.

Perhaps the most impressive action I have noticed is that of memory.  As one gets older, one’s memory becomes more difficult.  For years I have always had a problem with names, spelling, etc.  I have tried various techniques by keeping thoughts in compartments, house, or filing systems – a technique that was used by Roman lawyers.  All of my World War 1 and II hero’s names and histories are put into the downstairs room and drugs are put into another room etc. and this is a proven technique.  This helped but the matrix of this system fell apart and it would be a long time when I wanted to find a name or article for my memory to grind through a matrix that seemed to be declining.  Once a fact was found from the memory bank within a few hours it would be lost again, buried in what I visualize as a matrix of cells.  On Lithium, I seemed to have developed another matrix where when I have recalled a fact it stays in this new matrix like a new filing cabinet with easy access.  This fits it and this conclusion was made in retrospect with the idea that neurons regenerate and multiple especially in areas like the hippocampus.  In passing the only error I learnt that was erroneous was that the brain didn’t regenerate and your brain function was what you were born with and led to a steady decline as we aged.  We now know this is wrong, grey matter increases, cells can multiple, and new cells appear.

Before academics jump on this article, one should point out that most of the studies on Lithium in much higher doses in patients with Alzheimer’s Disease is in treating the plaque, tangles, etc. in short term studies and these grave stones are markers of past dysfunction, inflammation, etc. that took place perhaps a decade or more ago.  This error of short term Lithium against markers of chronic inflammation is like knocking down tombstones and expecting the corpse to rise. 

Lastly the effect on anxiety has made me less uptight or over-reactive but this hasn’t effected reactions while driving or playing sports.

Could this be a placebo reaction?  Unlikely after a latent period of two months.  We have one happy patient!

As in an earlier post, if Lithium is essential we have spent the last 50 years removing it from 7UP and our water supplies!

Lithium Deficiency

The media and the authorities are full of data on the increase in crime in many western countries, crime is often associated with extreme violence.  Documentation is important; however, little thought is given to the reasons.

Most Western countries are in a stable state, not at war, no extensive poverty, or obvious reasons for this increase. It is a vicious cycle as this increasing crime results in increased police hiring, etc. and so the cycle continues.  No one ever looks at the question why?

Certainly not a major cause, but an area that should be investigated is the question of Lithium deficiency in our water, food, even in tobacco.  There have been excellent studies have been carried out from Texas, Japan, and Lithuania that low intake of Lithium in areas with low Lithium in their water is associated with a whole spectrum of crimes ranging from drug addiction, rape, suicide etc.  Little thought seems to be given to these obviously sound statistical studies.

Why are we deficient in Lithium?  It is a good question to ask.  Is our intake of Lithium lowered from our water supply?  There is an increased tendency in many countries to abandon wells and use rivers, rainfall, etc.  These are obviously very deficient in minerals, particularly Lithium.  The increase in bottled water which contains no Lithium is another explanation especially since we seem to be developing an addiction to having water with us at all times.

Certainly, some attention should be focused on why we are deficient in Lithium and it would be very easy to carry out a survey of Lithium blood levels.  If the idea doesn’t pan out, it won’t have cost a fortune, harmed anyone but if the idea works it will have saved a lot of anguish, expense, and violence.