Maintain Your Brain, Part I: ALS, MS & Huntington's Disease (HD)
The Neurodegenerative Diseases Series (Part 1 of 3)
“ALS”, which stands for Amyotrophic Lateral Sclerosis and is also referred to as Lou Gehrig's disease is a type of motor neuron disease. It eventually leads to the inability to control movement, speech, and one’s ability to eat and even breathe, ultimately leading to paralysis. It has been described as a situation where one is “trapped in their body” and cannot move, but the mind is typically fully aware.
“MS”, which stands for Multiple Sclerosis is often considered an autoimmune disease. It eventually can drastically affect one’s movement, ability to swallow, vision and other symptoms, depending on severity.
“HD”, which stands for Huntington's Disease is a rare genetic disease. It can lead to uncontrolled movements, mood disturbances and cognitive issues such as a decline in memory and concentration.
All three of these are different diseases yet they share certain characteristics and are all considered Neurodegenerative Diseases.
This article “Maintain Your Brain, Part I” will be on these three diseases. Part 2 in this series on neurodegenerative diseases will be on Parkinson’s disease, and Part 3 will be on “Dementia”, more specifically Alzheimer's Disease.
These are all some of the most terrible, and terrifying, diseases someone can endure, as is the case with most diseases under the umbrella of neurodegenerative diseases. What makes these diseases even more tragic is that people often believe that there is nothing, or very little, they can do to prevent, treat or reverse the pathology. This sentiment is especially felt when it comes to HD. However, there are certain approaches people can take to attempt to help prevent, treat and potentially reverse these diseases and the associated symptoms.
Interestingly, caffeine seems to be beneficial for pretty much all neurodegenerative diseases, including ALS, MS and HD. So drinking a reasonable amount of coffee is a great idea in my book.
When it comes to ALS, it seems that one strong contributor is a very poor energetic state. This is a result of many things such as the brain’s poor ability to utilize glucose well, a low level of NAD, and excessive fatty acid oxidation. I discuss “how to utilize glucose well” in more detail in my article on the topic.
Vitamin B1, Niacinamide, and Aspirin have all been shown to have positive effects on reducing ALS symptoms. Vitamin B1, “Thiamine”, is essential for the body to be able to use glucose. It is a required nutrient for the enzyme pyruvate dehydrogenase “PDH" which is an extremely important enzyme in the process of taking glucose and using it effectively to create energy. Niacinamide has many positive effects when it comes to ALS. It is a direct precursor to NAD, it increases NAD indirectly by decreasing excessive lipolysis, thus decreasing excessive fatty acid oxidation, and it also indirectly helps with the utilization of glucose. Aspirin, similar to niacinamide, also can decrease excessive lipolysis.
“In any event, the human case study reported here demonstrated that 300mg benfotiamine daily induced a remission in many of the ALS symptoms in the patient, that the symptoms relapsed upon stopping the supplementation, and then remission was achieved once again when supplementation was resumed.”
-Georgi Dinkov in his blog Vitamin B1 (thiamine) may treat Amyotrophic Lateral Sclerosis (ALS) (references cited in the blog)
Creating enough energy is not all about using glucose well and having adequate levels of NAD, it is also a requirement to have adequate levels of FAD. This is likely why there is some evidence that Vitamin B2, “Riboflavin”, can be beneficial for ALS, as this vitamin, among other things, is needed for optimal FAD levels.
Another very important nutrient when it comes to energy production is the mineral copper. Copper is an essential nutrient for the function of the crucial energy-producing enzyme cytochrome C oxidase, a crucial step in the electron transport chain. So, consuming enough copper is essential, especially for those who are worried about developing ALS, and those who are currently suffering from ALS. Copper is very high in the livers of animals such as beef liver, and chocolate, and in shellfish/crustaceans/mollusks, most notably in oysters, calamari, octopus, shrimp and so on. In addition to copper, red light is important for cytochrome C oxidase, and there is some evidence that utilizing red light can be beneficial for ALS.
Amyotrophic lateral sclerosis (ALS) treated with low level LASER therapy (LLLT): A case report
Copper-ATSM as a Treatment for ALS: Support from Mutant SOD1 Models and Beyond
High cholesterol can be an issue in my opinion, but not because of the cholesterol itself. High cholesterol can be a classic sign of hypothyroidism because the active thyroid hormone, T3, is needed to convert cholesterol into steroid hormones such as pregnenolone. Be that as it may, having higher cholesterol levels in old age seems to be protective for many neurodegenerative diseases including Alzheimer’s disease and ALS. Furthermore, low cholesterol levels are correlated with an increased incidence of suicide. Take from this what you will, but I posit that trying to force cholesterol levels to be low via cholesterol-lowering drugs like statins is one of the worst things one can do, especially when it comes to “maintaining your brain”. So, while it is important to maintain adequate thyroid function and to have “normal” levels of cholesterol, one should try to avoid having low cholesterol, especially in old age.
Something that ALS and MS share is that they both seem to be exacerbated by polyunsaturated fatty acid “PUFA” metabolites known as eicosanoids. The Eicosanoids include Prostaglandins, Leukotrienes and Thromboxanes. The cyclooxygenase enzyme “COX” produces prostaglandins out of the PUFA, arachidonic acid (linoleic acid can be converted to arachidonic acid), the lipooxygenase enzyme “LOX” produces leukotrienes from arachidonic acid. Furthermore, phospholipases, such as phospholipase A2 “PLA2” release an abundance of arachidonic acid and can increase the activity of COX and LOX. Therefore, overactivation of PLA2 can lead to the overactivation of COX and LOX, thus leading to excessive amounts of prostaglandin and leukotrienes.
It seems that lowering the production or blocking the effects of these eicosanoids can be very beneficial for ALS and MS. So, for one, lowering the consumption of PUFA and increasing the consumption of monounsaturated fats and saturated fats would be a good long-term approach. This means, cutting out the margarine, sunflower oil, canola oil safflower oil, pork lard (pork and chicken fat can be very high in PUFA) and instead consuming more extra virgin olive oil, coconut oil, grass-fed butter and ghee and using beef tallow to cooking.
There are things people can do to lower PLA2 as well. Some herbs that help with this are Gingko Biloba, and Pine Bark Extract (Pycnogenol). Progesterone seems to help lower PLA2, as does vitamin E. There are also substances that help to lower the activation of the COX and LOX enzymes. When it comes to decreasing LOX or blocking the effects of leukotrienes Boswellia Serrata (Frankincense), Pycnogenol, Black Seed Oil, vitamin E and progesterone all have good effects. A classic COX inhibitor is aspirin, but things like progesterone and vitamin E can also lower COX activity and thus will lower prostaglandins. Some say that Stephen Hawking lived so long despite having ALS in part due to his aspirin use. I talk about lowering eicosanoids in more detail in my article on asthma, as leukotrienes are very involved in asthma.
While lowering the eicosanoids is helpful for ALS and MS, it seems specifically lowering or blocking the effects of leukotrienes is particularly beneficial when it comes to MS.
“Hypothyroidism can mimic the neurological problems of MS, but neurologists are generally willing to diagnose a condition as MS without giving thyroid tests.” -Ray Peat, Ph.D.
Many of the things discussed for ALS are also relevant for MS. Thiamine, Niacinamide, Red Light, Aspirin, and Caffeine/Coffee all seem to be beneficial for MS. In addition, active thyroid hormone, T3, taurine, NAC, sunlight and biotin all seem to be beneficial for MS.
Thyroid Hormone Mimetic Holds Promise as Remyelination Therapy for MS, Mouse Study Shows
Remyelinating Therapy Liothyronine Well-tolerated by MS Patients, Phase 1b Trial Finds
“In MS, it is clear that the inflammatory process itself is destructive, and that estrogen is a major predisposing factor. Unsaturated fatty acids, and dietary imbalance of amino acids interact closely with hyperestrogenism and hypothyroidism to produce the autoimmune degenerative diseases.”
“Mast cells, which promote inflammation by releasing substances such as histamine and serotonin (and make blood vessels leaky), are more numerous in the brain in multiple sclerosis than in normal brains. Since platelet clumping releases serotonin, and also because serotonin excess is suggested by so many other features of MS, serotonin antagonists (ondansetron and ketanserin, for example) have been used therapeutically with success.”
“Estrogen causes mast cells to release their inflammatory mediators, and it causes platelets to aggregate, releasing their serotonin. Since estrogen dominance is closely associated with the presence of active brain lesions, antiestrogen therapy would seem obvious in MS. Progesterone counteracts estrogen's effects on both mast cells and platelets.”
“Thyroid, progesterone, and pregnenolone are all involved in the formation of new myelin, and in the prevention of the edema that damages it.”
From “Multiple sclerosis, protein, fats, and progesterone”, Ray Peat, PhD
There are many questions left about the use of biotin for the treatment of MS, but overall it seems promising. Some studies have used 300mg of biotin for MS, the maximum dosage of biotin that can be purchased commercially is 10mg. When using biotin as a supplement, Ray Peat Ph.D. had mentioned in his book Nutrition for Women that it would be a good idea to increase one’s consumption of choline and to potentially supplement with inositol (presumably Myo-Inositol).
“Biotin is involved in the synthesis of fats in the nervous system, and so should probably be given special attention in the MS diet. Liver is a good source of it. If it is taken as a supplement, inositol (and probably choline) should be taken with it, because large doses of biotin by itself were toxic in animal experiments.”
Furthermore, MS is considered to be an autoimmune disease, and thus things that can be beneficial for autoimmune diseases in general may be useful for MS as well. You can read more about what can be done about autoimmune diseases in my article on the topic. Prolactin may also contribute to autoimmune diseases like MS, and thus different anti-prolactin strategies (like vitamin B6 and E) may be helpful. One thing I’d like to mention on this point is that the antibiotic minocycline, in low doses, seems to be very beneficial for autoimmune diseases, including MS. In low doses, minocycline is not acting so much as an antibiotic but is rather more of a very potent antiinflammatory exerting its effect in the intestines. Potent gut inflammation seems to certainly exacerbate MS, while also worsening other autoimmune conditions and neurodegenerative conditions. There is evidence that minocycline is useful for ALS and HD as well. What we can glean from this is that intestinal irritation and potentially bacterial overgrowth seem to play a role in the progression of many diseases, and decreasing gut irritation can likely be highly therapeutic. I go into this point in far more detail in my article on autoimmune conditions, linked earlier in this paragraph.
“Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury.”
From the review paper, Minocycline: far beyond an antibiotic
Also, the presence of excessive lactic acid and ammonia could worsen these diseases, especially MS. Low CO2, as a result of hyperventilation, poor glucose metabolism etc, will lead to high lactate/lactic acid and ammonia. The best way to make sure you are not getting into this situation is to use glucose well, as I describe in detail in this article.
“Hyperventilation causes increased vascular permeability, leading to hemoconcentration when a large portion of the blood's water escapes into the tissues. Vascular spasms, increased viscosity of the concentrated blood, and disturbed coagulation processes undoubtedly contribute to a wide range of health problems, including stroke, heart attack, and multiple sclerosis.”
“In hypothyroidism, with lowered oxidative metabolism, the organism is never far from stress and hyperventilation, with the chronic production of lactate and ammonia.”
-Ray Peat, Ph.D.
When it comes to HD it seems that the combination of vitamin B1 and Biotin are beneficial. As discussed prior, vitamin B1 is essential for the utilization of glucose especially via stimulating and being necessary for PDH. However, biotin is also a necessary nutrient for using glucose well, specifically, it is crucial for another enzyme, pyruvate carboxylase.
The drug amantadine, which is used for Parkinson’s disease and was originally used as an antiviral, seems to be beneficial for the treatment of HD (and MS). There are many possible reasons for this, one such reason could be the fact that amantadine is an NMDA blocker. Further, amantadine also has a pro-dopamine effect (hence its use in Parkinson’s). Amantadine is generally useful for autoimmune disorders.
“Some research has found increased serotonin in people with Huntington’s chorea (Kish, et al., 1987), and positive results with bromocriptine have been reported (Agnoli, et al., 1977).
“There are good reasons for thinking that serotonin contributes to the nerve damage seen in multiple sclerosis and Alzheimer’s disease.”
“The neurosteroid, allopregnanolone, for which progesterone is the precursor, facilitates the inhibitory action of GABA, which is known to be deficient in some disorders of mood and movement. This suggests that progesterone will be therapeutic in the movement disorders, as it is in various mood problems.”
From “Serotonin, depression, and aggression: The problem of brain energy”, Ray Peat, Ph.D
Lithium also seems to be useful for HD, ALS, MS and many other neurodegenerative diseases like Alzheimer’s and Parkinson’s. There are many reasons for lithium’s beneficial effects, such as the reduction of ammonia and the depletion of arachidonic acid in the brain, leading to fewer eicosanoids being produced. The prescription form of lithium is typically lithium carbonate. However, people can buy nutritional lithium supplements OTC in the form of Lithium Orotate. This supplement seems to be very effective for all sorts of conditions, and you can find out more info on its use in the book “Nutritional Lithium, a Cinderella Story”.
A retrospective review of lithium usage in veterans with multiple sclerosis
Off label use of lithium in the treatment of Huntington's disease: A case series
I want to quickly mention that vitamin D and agmatine seem to also be beneficial for this grouping of diseases. This is especially true if one’s vitamin D levels are inadequate. Also, the hormone pregnenolone is a very “brain-protective” hormone and would be a reasonable addition to any regimen used by someone with a neurodegenerative disease. Ray Peat, Ph.D. has even referred to pregnenolone as the“main brain protective” steroid hormone.
In conclusion, practically speaking, some very beneficial things one can try for the purposes of attempting to prevent, treat and perhaps reverse ALS, MS or HD are as follows:
Niacinamide (a form of vitamin B3, having different and better effects than plain Niacin)
Vitamin B1 (allithiamine/TTFD is likely the best for these purposes, maybe benfotiamine as well)
Aspirin
Lithium Orotate
Agmatine Sulfate
Vitamin D
Low-dose minocycline (prescription)
Amantadine (prescription)
Coffee/caffeine
Consuming enough copper
Progesterone (dissolved in vitamin E)
Pregnenolone
Red Light
Riboflavin (vitamin B2)
Thyroid hormone supplementation that contains T3
Biotin, with a source of choline (perhaps phosphatidylcholine) and maybe Myo-Inositol
LOX (and PLA2) inhibiting substances (Boswellia Serrata, Gingko Biloba, Pycnogenol, Black Seed Oil etc.)
Bromocriptine (prescription)
NAC
*None of this is medical advice. I am not a medical professional, always talk to your doctor*
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