Paracetamol and Alzeimer's Disease
Panadol and Alzeimer's Disease Link
By Walter Last, Health Science Spirit, Nov 2010
At first glance it sounds far out to link Alzheimer's disease (AD) to an apparently harmless over-the-counter analgesic (pain reliever) and antipyretic (fever reducer) that rely on paracetamol.
Paracetamol is called acetaminophen in the U.S. and Canada, and often sold under the brand name Tylenol. In Australasia, Africa, Asia, Europe and Central America paracetamol is sold under the Panadol label.
Unlike non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen and naproxen, which reduce pain and inflammation mainly by local action, paracetamol has recently been shown to work mainly by affecting the brain where it blocks the reuptake of analgesic cannabis chemicals or endocannabinoids. This only reduces pain without alleviating inflammation. It also gives us a clue as to why paracetamol is more likely to be associated with a degenerative brain disease than NSAIDs with their mainly local mode of action and anti-inflammatory properties.
That paracetamol is far from harmless can be seen from its tendency to cause kidney and liver damage. According to a recent study 'over use' of acetaminophen is the most common cause of acute liver failure in the United States. Paracetamol has a very narrow therapeutic index. The Therapeutic Index of a drug is the ratio of the toxic to the therapeutic dose. Therefore it is easy to overdose with paracetamol, and most liver damage has, in fact, resulted from unintentional overdoses, although intentional overdosing (suicides) is also common.
The maximum recommended daily intake is 4 grams but this amount already tends to cause liver damage, and since 2009 the FDA is contemplating to reduce the recommended maximum dose. Paracetamol overdose results in more calls to poison control centers in the US than overdose of any other pharmacological substance. Paracetamol is especially toxic to the liver if taken together with alcohol and then can easily be fatal. If taken during pregnancy Paracetamol can cause infertility in boys.
Untreated, overdose can lead to liver failure and death within days. The antidote for paracetamol overdose is acetylcysteine, (also called N-acetylcysteine or NAC). It is a precursor for the antioxidant glutathione which helps the body to prevent liver damage. Paracetamol is also lethal to cats and snakes. (1)
Until the 1970's phenacetin was the preferred analgesic and was converted in the body to paracetamol as its active ingredient. In the middle of the 20th century an epidemic of gastric ulcers and kidney disease occurred in Australia, and especially in Queensland, and was eventually traced to the addictive consumption of Bex Powder. Originally this contained aspirin, phenacetin, and caffeine but in 1976 phenacetin was replaced with paracetamol. It was the mood-altering drug of choice for young women (2).
The Alzheimer's Connection
Originally, since the 1880's, phenacetin, an aniline derivative, was widely used as an analgesic. The consumption of phenacetin and other analgesics increased steeply after World War II. In 1971 the first paper was published that linked high use of phenacetin with the development of Alzheimer's disease (3). Autopsies were performed on a series of individuals who died of kidney disease caused by high intake of analgesics (analgesic nephropathy).
Senile plaques were found in six individuals aged from 52 to 67 years who had lifetime high intakes of phenacitin, while no plaques were seen in two subjects aged 68 and 72 years who had consumed similar amounts of aspirin over their lifetimes, but no phenacetin. The main point is that phenacetin forms paracetamol in the body as its active metabolite. For this reason and because of its high kidney toxicity, phenacetin was eventually replaced by the direct ingestion of paracetamol.
The Abstract of this paper reads: "Psychometric and psychiatric studies on eight patients who had abused compound analgesics containing phenacetin showed that four had definite evidence and two possible evidence of organic dementia. Neuropathological studies on nine other analgesic abusers disclosed a surprisingly high incidence of the histological features of Alzheimer's disease. It is suggested that gross abuse of phenacetin may overwhelm the antioxidant protection of the body, leading to premature deposition of lipofuscin, and accelerated neuronal ageing."
This study was not followed up by other researchers or health agencies. But some time later a 'strange' incident happened to Robert Jones that made him dig more deeply into the possible link between paracetamol and AD. Robert Jones (PhD) worked mainly as a British cancer researcher who fell out with the establishment when he published his protocol for the treatment of cancer with promethazine, an antihistamine also known as Phenergan. (4)
Twenty years ago he took paracetamol for about 10 days to alleviate pain while painting his house. Two weeks later he noticed short and long-term memory problems. Gradually these improved again but ten years later the same sequence repeated itself. That pricked his curiosity and he started looking into a possible connection between paracetamol and AD. The result of his research was an article in Medical Hypothesis in 2001. (5) This did not make much of an impact, and so he recently wrote another article: Does placing the histories of certain analgesics and Fischer-Alzheimer's disease (F-AD) in relative alignment reveal connected pharmacological risk factors? But this time the paper was not even accepted by a medical journal. (6)
The Timelines of AD and Paracetamol
The term Alzheimer's disease was coined in 1910 for an unusual form of early-onset dementia. It had been independently recognised in 1901 by Oskar Fischer in Prague and then by Alois Alzheimer in Frankfurt. Fischer's first patient died in 1903; Alzheimer's in 1906. The cortex of each patient showed rare plaque-like lesions. Both published their findings in 1907. Despite intensive search, only 12 instances of plaques in dementia patients had been found before 1907. Over the next 5 years 115 new cases were discovered, Fischer described 56 of these.
Compare the timing of these events leading to the recognition and definition of AD to the introduction and use of phenacetin. Both phenacetin and paracetamol were first tried on patients in 1887. At that time phenacetin became the preferred drug, and its sales established Bayer as a leading pharmaceutical company. Originally very high doses were recommended by some doctors. Use of phenacetin spread internationally on a large scale as a result of the 1889-90 Asiatic influenza pandemic. At the same time also its kidney toxicity became apparent.
By comparing the two timelines we see that the introduction and widespread use of phenacetin preceded the sudden appearance and explosive spread of AD by one or two decades. Also these early AD victims typically displayed the kidney damage characteristic of phenacetin overuse. Another indication of a possible causal connection is the statistical fact that presently paracetamol use and AD incidence are almost twice as high in women than in men.
Originally phenacetin and later paracetamol were mainly used and produced in industrialised countries and that is where AD initially flourished. But in more recent years (2008) production has stopped in Europe and is now mainly based in China and India which presently also have the highest projected growth rates of AD. The estimated annual world production of paracetamol is about 145,000 tonnes. That is an awful amount of tablets to swallow, and at the maximum dose of 4 g/day sufficient to control chronic pain of about 100 million people. It also shows us where the incidence rates of AD may be heading; in 2010, about 35 million cases of AD exist world-wide.
So far, indications are that a high intake of paracetamol for extended periods is required to lead to the development of AD. With 51% the use of paracetamol in dementia patients was found to be higher than with 21% in non-demented controls. In some more recent studies aspirin and other NSAIDs had a moderately protective effect on the development of AD, but paracetamol use of more than 2 years increased the risk by about 50%. However, these were short-term studies and it was not specified if paracetamol use was occasional and light, or chronic and heavy. (6)
We may assume that the risk of developing AD is a function of several factors, including the lifetime intake of paracetamol, the ability of the liver to detoxify the substance, and the kidneys to excrete the residues. Therefore someone with liver or kidney damage, or burdened with the ingestion of other drugs, or exposed to mercury, can be expected to develop AD at much lower doses than someone who is reasonably healthy and does not normally use any other drugs.
There are three metabolic pathways in which the liver can detoxify paracetamol, and one of these pathways can produce a toxic metabolite which may accumulate with high intakes and certain genetic and metabolic conditions. Therefore it is clear that the accumulated dose of paracetamol that may trigger AD can be expected to vary widely between individuals.
Furthermore, there is no reason to believe that paracetamol may be the only drug or environmental chemical that can cause AD-type brain damage. Not only individual drugs and chemicals but their combinations may cause or contribute to AD. We do not know anything about this, so far no one has investigated.
One telling example is the 'accidental' finding that small amounts of the common herbicide paraquat and the fungicide maneb are apparently harmless when fed to animals individually but when given together to rats and mice, even at very low rates, they produced the symptoms of Parkinson's disease. These chemicals are widely used in farming and may remain present as crop residues. The leader of the research team said: "No one has looked at the effects of studying together some of these compounds that, taken by themselves, have little effect. This has enormous implications," and "it's a huge problem to start thinking about a nearly infinite array of mixtures of chemicals, instead of the risk that a single chemical might pose". (7)
Perhaps residues of paraquat and maneb also cause or contribute to the development of AD? Who is responsible for finding out and allowing only safe combinations of drugs and chemicals into our food chain? Obviously the safe way to minimise our chances of developing AD is to minimise our exposure to all drugs and questionable chemicals! Even occasionally taking relatively harmless drugs to treat insomnia and anxiety has recently been shown to increase mortality risk by 36% (8).
We have government health agencies that are supposed to ensure the safety of drugs. So far, after over one hundred years of medical use, no proper safety checks have been made for phenacetin or paracetamol, especially in regard to the possibility of causing or contributing to AD.
For that matter no proper safety checks have been done for other drugs either. Drug companies are just required to do some short-term studies with single drugs and often on healthy individuals. From this the medical system deduces in an act of magical thinking that such drugs are then safe when used in the long-term or for a life-time, and/or if used by individuals with weak liver or kidney functions, and/or with impaired metabolic or detoxifying abilities, and/or when used in combination with various other drugs and chemicals. In a few cases drugs may be curtailed or withdrawn after a few decades when a sufficient number of patients have needlessly died, but overall no one knows how much morbidity or mortality is caused by long-term drug use in varying combinations for different conditions.
One class of drugs that does frequently cause deterioration or loss of memory are the statin drugs prescribed to lower cholesterol levels. Dr Graveline, a NASA astronaut, flight surgeon and family doctor wrote that he suddenly had a temporary complete loss of memory after six weeks of using Lipitor. He collected statements from others who had been similarly affected. It has been proposed that high or elevated cholesterol levels protect the brain from deterioration. (9)
Other frequently claimed causes or contributors to the development of AD are lack of long-chain omega-3 fatty acids, specifically DHA; mercury from dental amalgam, seafood and vaccinations, and aluminium from cookware, baking foil, processed foods, baked goods, baking powder, brewed drinks, drinking water, some antacids, and anti-perspirants. Other factors are mentioned as being lead, mobile/cell phones, solvents, fungi and parasites, sugar, chlorinated water, inhalant anaesthetics, and excitotoxins (e.g. MSG). A good overview of these factors with some references is at Alzheimer's Disease: On Suggested Causes and Cures. (10)
Bernard Windham (Biostatistician) collected hundreds of scientific references on the toxic effects of mercury and also aluminium as a cause of AD and other neurological and autoimmune conditions. Accordingly, a major factor in the neurotoxicity of mercury are decreased levels of glutathione peroxidase and superoxide dismustase which lead to increased lipid peroxidation in the brain. Even a few micrograms of mercury can severely disturb cellular functions. Mercury also accumulates in the mitochondria and interferes with their vital functions, especially by inhibiting cytochrome C enzymes and reducing energy supply to the brain. (11)
In regard to mercury and aluminium in vaccines we can read: "A study of people who received flu shots regularly found that if an individual had five consecutive flu shots between 1970 and 1980 (the years studied) his/her chances of getting Alzheimer's Disease is ten times higher than if they had one or no shots". (12)
The Niacinamide Cure
A study of mice with induced AD restored their full memory after treatment for four months with the human dose equivalent of 2000 to 3000 milligrams of niacinamide, also called nicotinamide or vitamin B3. Niacin or nicotinic acid belongs to this group as well but it tends to induce flushing, and some may be reluctant to take it, although it is the recommended form to lower cholesterol and triglycerides in the blood.
"Cognitively, they (the mice) were cured," commented the leading researcher. "The vitamin completely prevented cognitive decline associated with the disease, bringing them back to the level they’d be at if they didn’t have the pathology." In addition, niacinamide also improved the memory of mice without AD. Presently there are several human trials with niacinamide in progress. (13)
It is no real surprise that vitamin B3 is beneficial because it works also in many other conditions, such as improving or normalising schizophrenia, senile conditions, arthritis, hyperactivity or behavioural and learning difficulties of children, cholesterol problems, cancer, dermatitis, juvenile diabetes, fatigue and lack of energy (14). The reason why a single vitamin can help with all of these problems is its key role as a coenzyme in oxidative cellular energy production.
If certain areas of the brain or the body are congested with metabolic waste products or for other reasons have reduced blood supply, then energy production in that part of the body is reduced. The brain needs 20% of our total energy to function properly and therefore is especially sensitive to lack of energy.
An indication of the degree of biological aging is the amount of lactic acid accumulating in the brain. This is especially pronounced with degenerative brain diseases such as AD and Parkinson's disease (15). Lactic acid is formed when the oxidative energy production in the mitochondria, the powerhouses inside cells, declines. In AD niacinamide-dependent enzymes have been shown to be deficient (16). Getting more niacinamide into congested brain cells helps to rev up energy production and lets these cells function more normally.
There may be an additional reason related specifically to paracetamol in its function as an antipyretic. This means paracetamol lowers the body temperature, and it may do this by lowering the temperature in a specific part of the brain by reducing the energy metabolism in that area. Niacinamide has the opposite effect - someone who does not produce enough body heat, and easily feels cold with cold hands and feet, can often improve or overcome this problem by taking high-dose niacinamide supplements.
However, even if niacinamide works as well in humans as it does in mice, it is not likely to be a permanent solution. In most of the mentioned conditions high doses need to be continued indefinitely or until the primary blockage in energy production has been removed.
Other Useful Measures
Niacinamide works best when also supplying other vitamins of the B group at lower doses, such as taking a B complex with most meals. In addition, vitamin B12 is especially useful. In AD studies B12 has commonly been tested together with folic acid and vitamin B6.
These B vitamins control levels of the amino acid homocysteine in the blood. Homocysteine is formed during the conversion of the amino acid methionine into the functional amino acid cysteine. When these vitamins are deficient high levels of homocysteine accumulate which are associated with an increased risk of AD. Supplementing these vitamins can halve the rate of brain shrinkage in elderly people with mild memory problems. Those with the slowest rate of shrinkage had better cognitive test scores. (17)
However, vitamin B12 is poorly absorbed. especially by the elderly. If one does not want to get regular injections of B12 one can chew a tablet and keep it under the tongue for as long as possible, or dissolve it in a small amount of warm water to make a paste and rub it into the nostrils for absorption. If done daily only a small amount needs to be used. Better than folic acid from tablets is folate from green leaves or their juices.
Other beneficial vitamins and minerals are high amounts of vitamin C, D (sunshine) and (natural) vitamin E, magnesium, zinc, iodine and selenium. Lecithin, gingko biloba and turmeric are beneficial for brain and liver, while caffeine stimulates brain activity. A recent supplement to the Journal of Alzheimer's Disease showed that the consumption of moderate amounts of caffeine slowed the cognitive decline associated with aging as well as the incidence of AD (18).
Acetyl-L-Carnitine or ALCAR (try 1 - 2 g/day) increases energy production by delivering fatty acids into mitochondria and improves their health by helping to dispose of fatty wastes. It also increases production of the important neurotransmitter acetylcholine. Before Alzheimer's patients experience memory loss, the brain's neurons have already suffered harm for many years due to their mitochondria being congested with protein and fat residues (19).
The omega-3 fatty acid DHA (docosahexaenoic acid) is the most abundant fatty acid in the brain. People with liver damage (as from paracetamol) have lost the ability to synthesise it from the more common alpha linolenic acid. Therefore supplementing with DHA tends to be beneficial but it needs to be given together with protective vitamin E as oxidised DHA may damage the brain.
Other studies show that a low dosage of a certain cannabinoid, a component in marijuana, reversed memory loss in older rats. These old rats performed better in memory tests, and had less brain cell death. It has also been found that people who regularly smoked marijuana in the 1960s and 1970s rarely develop Alzheimer’s disease. Earlier research (2006) showed that THC, marijuana’s active ingredient, can slow the formation of "Alzheimer plaques" in the brain better than any commercial drugs. THC also blocks clumps of protein that inhibit memory and cognition in AD patients. (20) These beneficial effects of cannabinoids may be significant as paracetamol has been shown to work by blocking our internal cannabinoids in the brain.
To improve blood supply to the brain it is beneficial frequently to lie for extended periods with the head lower than the heart such as on a slant board or by raising the foot end of the bed with bricks.
The Real Cure
Medical research clearly shows that a major factor in the development of AD are large amounts of abnormal proteins deposited in neurons and other brain areas. In addition there are also oxidised lipid wastes and toxic metals. It is clear that these more or less toxic waste accumulations will greatly limit nutrient supply, waste removal, and energy production in the affected areas of the brain.
While mainstream medicine will continue to search for new and better drugs and technologies, for natural medicine this is a standard problem with a time-honoured solution. Essentially all chronic degenerative diseases present us with the same picture of accumulated metabolic and toxic waste products that obstruct normal cell and organ functions. The main difference between the multitude of diseases is the organ or part of the body that is most affected and the way in which body functions are impaired.
The process by which cells degrade and recycle material into amino acids that can be reused is called autophagy. It is an essential component of cellular survival and defence against invading organisms. Even mainstream researchers realise that waste removal is the potential cure and that calorie restriction encourages autophagy but it is more profitable to look for a drug or technological solution to accomplish this (21).
If the affected cells could break down the obstructing plaques that would greatly increase the chances of recovery from AD. A researcher explained: "Although we do not yet completely understand how these diseases develop, we do know that the proteins clump together and form a plaque build-up in affected patients' neurons. If we can direct the cell's own ability to break down waste products against the plaques, we could keep them from forming and potentially intercept the development of these and other diseases," (22).
Furthermore, most chronic and autoimmune diseases are associated with the presence of pleomorphic or cell-wall deficient microbes in the affected tissues, and there is some indication that this is also the case with AD. For instance by experimentally using a drug that is approved for immune deficiency and autoimmune disorders researchers achieved much better results than with any drug approved and used for treating AD (23). This shows the potential benefit of treating AD like an autoimmune disease. For a more detailed explanation see my article How to Overcome Chronic and Autoimmune Diseases (24).
While cleansing is difficult even for determined individuals who want to improve their health, it is even more so for AD patients and their carers. Nevertheless, it is the only game in town, and some carers or even individuals with early symptoms may want to try. So here is a basic outline of a holistic program.
Step 1: Avoid or minimise the factors that have been mentioned as causing or contributing to the condition, e.g. any mercury amalgam fillings still present should be removed, preferably by an holistic dentist. Gradually reduce any drugs to the absolute minimum, food should be as free of chemical additives or residues as possible.
Step 2: Gradually introduce vitamins, minerals and other remedies mentioned as being beneficial, especially remedies and methods that improve liver functions and blood circulation to the brain. Try 500 mg of niacinamide with each meal, possibly double the dose. If niacinamide therapy is reasonably successful, that will make the whole program so much easier to follow.
Step 3: Monitor the acidity of the urine and try to keep it close to pH 7. If it is mostly too acid then give more alkalising agents, including sodium bicarbonate (not close to meals) and potassium citrate. If the body seems to be too alkaline, pH above 7, and skin insensitive to irritants such as insect stings, then give more ascorbic acid, and hydrochloric acid supplements with meals.
Step 4: Gradually adopt a High Quality Diet (25).
Step 5: Use oral chelation to remove mercury and aluminium. Sulphur compounds are needed to detoxify the liver. If these are not well tolerated, add a molybdenum supplement. One of the strongest chelators is alpha lipoic acid (also called thioctic acid), best combined with milk thistle extract. Chlorella (cell broken powder) prevents re-absorption of expelled metals from the intestines. Also helpful are MSM, N-acetylcysteine, alpha-tocopherol, and ascorbic acid. You may also add other mercury chelators obtained from the Internet or use the Klinghardt Neurotoxin Elimination Protocol (26).
Step 6: To reduce or eliminate microbial problems try a mild form of the Ultimate Cleanse (27) with special focus on using lactic acid fermented foods, especially fermented vegetables such as genuine sauerkraut.
Step 7: A series of cleanses on fresh raw food is needed to remove the toxic and metabolic waste products from the brain. This is the most difficult part and needs to be done gently with only gradually increasing intensity. When under-eating the body starts to process, digest and eliminate its waste products but only if it has enough vitality which can best be supplied with fresh juices of wheat grass and barley grass as well as sprouted seeds (mung beans, lentils). In addition protein-digesting enzymes are helpful, e.g. bromelain and papain (28).
Ideally governments would encourage and support the establishment of sanatoriums and health farms for the holistic therapy of patients with AD and other chronic diseases. But sadly government health agencies are firmly wedded to drug medicine and have a long track record of suppressing natural medicine. Examples of this are the persecution of holistic cancer therapists (29) and the malicious destruction of Pan Pharmaceuticals in Australia (30).
Therefore, it is clear that any attempt at setting up community healing ventures needs to start from the grassroots level and proceed very carefully. A model for this exists in the movement started by Ann Wigmore in the 1960's that led to the establishment of Hippocrates Health Centers. There visitors could detoxify and heal on a raw food program based on fresh wheat grass juice and sprouted seeds. This movement included city centers as well as health farms. It would be great if this movement or something similar could be revived and made to spread worldwide.
(1) http://en.wikipedia.org/wiki/Paracetamol - on this page you find references for the mentioned statements
(6) http://www.commonsenseincancer.co.uk/images/paracetamol-azheimer.pdf with references for the mentioned statements
Author's website: http://www.health-science-spirit.com/paracetamol.htm