I recently wrote about my experiences of severe brain fog and memory impairment for Hormones Matter (Thiamine Deficiency: A Slow Road to Dementia), and how oral thiamine had no effect on my symptoms, but IV thiamine and benfotiamine, a fat-soluble thiamine analog, resolved them. There have been far too few studies of thiamine in patients with Alzheimer’s dementia, with thiamine taken too late, for too short a time period, but generally, thiamine has not been that beneficial, yet benfotiamine is potentially effective. Based on the fact that I had abnormal guts and evidence of bacterial overgrowth, I hypothesized that bacteria in the gut destroy thiamine preventing it from being absorbed and that benfotiamine circumvents this problem.
One reader of this article very helpfully reported back to me that her husband takes high-dose thiamine for Parkinson’s disease and that, like many patients, he finds it helpful. Looking into this in more detail I read that there are low levels of thiamine in the cerebrospinal fluid—the fluid around the brain—in patients with Parkinson’s disease. There is also reduced glucose metabolism in the brain, similar to Alzheimer’s, as thiamine is required for the normal breakdown of glucose to release energy. There are several strong indicators that thiamine pathways are involved in Parkinson’s disease. Thiamine can be given by intramuscular injection or taken in high doses orally. According to patients’ reports online up to 4g per day of thiamine HCL is required orally to show an effect. This wouldn’t fit with my hypothesis of gut bacterial destruction of thiamine in Parkinson’s disease, and interestingly thiamine levels in the blood have been found to be low in Alzheimer’s disease and not reduced in Parkinson’s disease.
So how does thiamine work in Parkinson’s disease and why are high doses seemingly effective? I suspect the underlying cause of non-hereditary Alzheimer’s disease is thiamine deficiency, but what actually causes Parkinson’s disease?
Parkinson’s disease is the fastest growing of the neurodegenerative diseases—doubling in the past 25 years. It was first described by James Parkinson in London in 1817. According to the Global Burden of Disease Study Canada had the highest number of cases of Parkinson’s disease in the world in 2016. Why is this? Environmental pollution in newly industrialized countries is linked to this rise in cases, but I believe that the role of mercury, and its impact on thiamine and glucose metabolism, is currently massively underestimated.
Environmental Pollution and Neurodegenerative Disease
I would like to digress and draw your attention to two recent issues here in the UK, as I believe they have a role in the development of neurodegenerative diseases like Parkinson’s.
In October 2021, residents at Seaton Carew, County Durham, Northeast England, reported that a large number of dead crabs were washing up on the beach. Lobsters and seabirds were also dying; even dogs being walked along the beach were becoming unwell and vomiting. Before dying, the crabs and lobsters were described as twitching and staggering, as though their nervous system had been affected. People thought the shellfish had been poisoned. A few months later dead seals washed up on the beaches appearing starved. Locals believe it may be related to dredging the mouth of the Tees, a large industrial river estuary, in order to make a post-Brexit Freeport. According to fishermen, the slurry was dumped in the North Sea, 3 miles off the coast. The Tees estuary has historically been an area with many industries; with a coal-fired power station in operation for decades, until 2007, and an ICI factory, which opened in 1952, was the largest British chemical plant at the time. Pyridine levels were found to be high in the shellfish but were not thought to be the cause of the mass dying. Some blamed it on an algal bloom, but algae were unlikely at that time of year. I am concerned that deep dredging disturbed mercury deposits and the sea creatures are dying from acute mercury poisoning.
Another problem, not completely unrelated, is the release of raw sewage into the waterways. There have been multiple reports on the discharges of raw, untreated sewage pouring into our rivers, lakes and seas. The levels of pollution are considerably higher in the North of England. It would seem that our Victorian sewers are no longer capable of coping with the amount of sewage produced by a much-expanded population since the Victorian times. Private water companies are responsible for providing this service, and they have been repeatedly fined for breach of contract. Human sewage has been contaminating our waterways and coastal areas. This is not unique to UK; it is also happening regularly in America and elsewhere. It is worse when there are floods. It has been known since 1854 that human sewage causes epidemics of human disease when John Snow investigated the Broad Street pump; back then it was cholera. Now I’m concerned that it is contributing to the increase in neurodegenerative diseases through the conversion of mercury to the more toxic methylmercury.
Mercury, Bacteria, and Parkinson’s: Is There a Connection?
There is a theory that chronic mercury toxicity causes Parkinson’s disease. I have a silver-mercury amalgam root filling, and I researched whether this was contributing to my symptoms as I had a prominent tremor. I also became concerned about sewage spills because I thought that the bacteria destroying thiamine in my gut might have spread through drinking contaminated water.
Studying two maps as part of my research for another book I was writing, I noticed a pattern, with flood-prone states in the US having higher numbers of cases of Parkinson’s disease. However worldwide there was more of a link with burning coal. These are the top ten coal consumers in the world: China, India, USA, Japan, Africa, South Korea, Russia, Germany, Indonesia and Poland. These are the top five countries with the estimated highest prevalence of Parkinson’s disease in 2020: China, USA, Japan, Germany and Brazil. There is massive use of coal in China; currently almost 50% of global coal use is in this country. There has been a dramatic increase in Parkinson’s disease here, so much so that it is estimated by 2030 almost 50% of global cases of Parkinson’s disease will be in China.
Interestingly, mercury has recently been detected in the nerve cells in patients with Parkinson’s disease. Specifically, it has been found in the regions of the brain—the dopamine-producing substantia nigra—affected in Parkinson’s disease. It was detected in the same parts of the brain as Lewy bodies—abnormal clumps of the protein alpha-synuclein, typical of Parkinson’s disease.
A little background information is required on mercury. Mercury is a heavy metal. It is not useful in the body, unlike several heavy metals that do have a function. Any amount of mercury is potentially toxic. There are no natural mechanisms to rid mercury once it has been taken up. Over time, the amount of mercury in the body gradually increases.
Burning fossil fuels, particularly coal—like on the Tees estuary in the past or in China now—releases mercury into the air, onto land and water. Atmospheric mercury is also increased by artisanal (independent) gold mining, metal mining—particularly mercury mines, and then naturally, by volcanoes. Mercury binds strongly to gold—hence its use in gold mining. When the gold-mercury amalgam is heated this releases the mercury. It also binds to sulfur—hence its past use in the dental industry as a silver-mercury amalgam.
Mercury is converted to the more toxic methylmercury by bacteria in water. Bacterial contamination of water is more prevalent with sewage pollution—discharges of raw sewage into our rivers and seas, flooding, or after building dams for hydroelectricity. Methylmercury is much better absorbed through our gut and skin, as well as by sea creatures. The amount of mercury accumulates with exposure. It also accumulates up the food chain as the big fishes eat the little fishes; hence there is more mercury in large fishes and fish-eating mammals, such as seals, and humans.
Mercury, Thiamine, and Mitochondrial Function
Some years ago a number of patients experimenting with the synthetic heroin MPTP developed an illness like Parkinson’s disease. This recreational drug actually disrupts the function of the first protein or complex I on the mitochondrial membrane in the electron transfer chain—a series of proteins producing the high-energy carrier ATP. Paraquat, the weed killer, is also known to cause Parkinson’s disease, and similarly disturbs this complex I.
Recall, the mitochondria are the powerhouses of the cells in the body—miniature battery packs in every cell. These battery packs are designed not to leak and to keep the highly reactive iron and oxygen safely shut away where their function is to produce the energy required by the cell. Damage to complex I leads to leakage of iron and oxygen. A typical feature seen in the brain in Parkinson’s disease are high iron levels and charged oxygen molecules—both are highly reactive, and promote clumping of the alpha-synuclein seen in Parkinson’s disease.
Mercury binds strongly to the sulfur-containing cysteine residues of proteins, adversely affecting their function throughout the body. In the mitochondria mercury binds to the disulfide bond in the cofactor lipoic acid, which is essential for several mitochondrial enzymes, including the pyruvate dehydrogenase complex (PDC) and the alpha-ketoglutarate dehydrogenase complex (KGDH). Dysfunction of the PDC blocks the formation of acetyl-CoA, the critical first step in the metabolism of glucose to produce ATP. KGDH catalyzes the conversion of alpha-ketoglutarate to succinyl-CoA, producing NADH—another high energy carrier, which provides electrons for the more powerful energy generator, the electron transfer chain on the inner mitochondrial membrane.
The two sulfur atoms in lipoic acid are reversibly reduced to form thiols—SH groups. Using this redox (oxidation—reduction) ability of lipoic acid KGDH acts a key regulatory enzyme in the Kreb’s cycle. Its activity responds to the level of NADH and the presence of highly reactive oxygen molecules—reactive oxygen species (ROS). It acts as a redox sensor, leading to down regulation of this enzyme complex, which protects the mitochondrial complexes on the inner membrane from oxidative damage.
Thiamine and lipoic acid work in tandem in the PDC and KGDH enzymes, both are essential, hence deficiency or dysfunction of either cofactors adversely affects the function of these enzymes. This explains why there are similarities clinically between thiamine deficiency and mercury poisoning.
Mercury also binds to iron-sulfur clusters in the complexes of the mitochondrial electron transport chain; the majority of these clusters are found within complex I. As seen with MPTP and paraquat poisoning, disruption of complex I leads to Parkinson’s symptoms. As well as their role in electron transfer and energy generation, these iron-sulfur clusters are able to regulate the genes involved in dealing with oxidative stress and excess iron.
The binding of mercury to complex I would lead to the cascade of events, the generation of reactive oxygen species and toxic free iron, which are promoters of alpha-synuclein clumping seen in Lewy bodies, disrupt the safety mechanisms designed to limit damage, as well as reducing energy production, which makes neurons even more vulnerable.
Parkinson’s — Evidence Incriminating Mercury
There was a mass poisoning event that occurred in Minamata in the 1950s after a local chemical factory discharged mercury into the bay. This was the topic of a recent film, also called Minamata. The fish died, the birds fell out of the sky and the cats danced. Minamata, like the rest of Japan, is predominantly a fish-eating community. First the disease affected the animals and then it affected the local people, who became unwell with a strange neurological illness, and babies were born severely deformed. Sufferers were ostracized at first in case the condition was contagious. Many developed neurodegenerative diseases and there is a high prevalence of Parkinson’s disease in Japan. A chemical factory had been discharging mercury into the bay. For many years those in authority tried to deny that there was any evidence of pollution.
Back in the UK, deep dredging of the Tees channel will have stirred up centuries of industrial pollutants, including mercury. Bacteria in sewage react with mercury to produce the more toxic form methylmercury. London in 1817, when Parkinson’s disease was first found to be a problem, was the coal-burning center of the world and the River Thames was heavily polluted with raw sewage.
Historically Canada has had a high prevalence of Parkinson’s disease. It had problems with mercury pollution after a chlor-alkali factory disposed of mercury into the waterways. Brazil also has a high prevalence of Parkinson’s disease and many small-scale gold mines leading to mercury pollution of the fish.
I have now come across three cases of Parkinson’s disease occurring at a young age in people wild swimming in potentially mercury-contaminated waters (personal communication). I have also read about a large number of cases of mass deaths of animals or fish that are reliant on either a specific body of water or on a fish diet. Often the deaths are attributed to an overgrowth of algae—algal blooms—and yet no toxin is detected. Algal blooms are the result of excess nutrients and warmer temperatures, which leads to marked reduction in the oxygen and thiamine levels in the water. Mercury from natural and anthropogenic sources is transformed into methylmercury by anaerobic bacteria, typically sulfate-reducing bacteria. These bacteria that thrive in the anoxic waters resulting from algal blooms, are the major producers of methylmercury in our rivers, lakes and seas.
Parkinson’s Disease and Thiamine
So, Parkinson’s disease is more prevalent where coal is burnt, mercury has been found in the brain in patients with Parkinson’s disease and mercury toxicity could explain the damage seen in Parkinson’s disease, but what is the connection to thiamine?
Mercury impairs two thiamine-dependent enzymes, PDC and KGDH, which significantly reduces mitochondrial energy capacity. It’s not a great surprise that mercury toxicity and thiamine deficiency present with similar symptoms, most commonly tremor and fatigue.
Mercury also disrupts complex I of the electron transfer chain causing a cascade of events leading to increased reactive oxygen and free iron. Dopamine, the neurotransmitter found predominantly in the substantia nigra, isn’t stable; oxygen and iron lead to the production of a dopamine metabolite that promotes clumping of the alpha-synuclein, possibly explaining why the dopamine-producing nerves of the substantia nigra are most vulnerable to developing Lewy bodies. In the brain the substantia nigra is particularly important for control of movement.
As shown by Costantini, high-dose parenteral thiamine therapy led to a marked improvement in the motor symptoms, particularly muscle tone, but also fatigue and pain, in patients with Parkinson’s disease. This was despite having normal blood levels of thiamine. The initial three patients he described had not started other medications for Parkinson’s disease.
Thiamine levels in the blood in Parkinson’s disease are normal. Thiamine consists of a pyrimidine ring attached to a sulfur-containing thiazole ring. This thiazole ring attaches to the phosphate groups and the presence of phosphate is required for the thiamine to be active. It is feasible that mercury effectively disables thiamine by binding to the thiazole ring, perhaps this leads to a functional systemic deficiency, which can be overcome with high doses.
Thiamine levels in the fluid surrounding the brain are lower in Parkinson’s disease. As mercury also impairs antioxidant capacity, it reduces the body’s ability to mop up toxic oxidants, like the mercury-induced iron and oxygen leak in complex I of the ETC. Thiamine is an antioxidant and its effectiveness in Parkinson’s disease maybe through this mechanism, resulting in lower levels locally as thiamine is used up.
There are other antioxidants, for example vitamin C, and some patients with Parkinson’s disease have reported online that there is some benefit in taking vitamin C. Another antioxidant is glutathione, levels of which can be increased by taking N-acetylcysteine, which also seems to improve symptoms.
Costantini thought that Parkinson’s disease was due to two separate processes, which were both dependent on thiamine: a severe, focal dysfunction in addition to a low-mild dysfunction. He claimed that thiamine therapy resulted in an improvement in both the motor symptoms and fatigue, and that this effect was due to thiamine working on these different pathways. I wonder whether the ‘severe, focal damage’ could be the impairment of the complex I in the ETC, resulting in the cascade of events leading to the destruction of the substantia nigra, whilst the ‘low-mild dysfunction’ could be due to the impairment of the thiamine-dependent enzymes involved in glucose metabolism and energy production. Interestingly the patient who had developed symptoms most recently had benefitted the most from high-dose thiamine therapy; perhaps there had been less permanent damage in the substantia nigra.
Can Parkinson’s Disease Be Prevented?
Prevention is better than cure. How can we prevent mercury pollution in general and hopefully reduce the burden of Parkinson’s disease? The researchers who detected mercury in the brain in patients with Parkinson’s disease concluded that we should stop burning fossil fuels. In particular, we need to stop burning coal. We also need to be aware of the potential danger of eating fish, crack down on illegal gold mining, minimize sewage contamination of water sources, and dispose new industrial waste safely and not disturb old industrial waste.
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This article was published originally on October 17, 2022.