Maintain Your Brain, Part II: Parkinson's Disease (PD)

The Neurodegenerative Diseases Series (Part 2 of 3)

Apr 11, 2024

“Most of the things that are likely to be protective in Parkinson's disease are broadly protective against estrogen and the inflammatory degenerative processes: Progesterone, minocycline and other anti-inflammatory antibiotics, agmatine, aspirin, coffee, niacinamide, citrus flavonoids, vitamin D, ACE inhibitors, fibrous-antiseptic foods [raw carrot salad as an example].”

- Ray Peat, Ph.D

Parkinson’s disease (“PD”), formerly referred to as “shaking palsy” is a neurodegenerative disease which can include tremors, stiffness, slowness of movement, speech changes and loss of automatic movements. It’s more common in men. Some consider PD to be an autoimmune disorder, or at least partially caused by an autoimmune reaction.

This article “Maintain Your Brain, Part II” will be on Parkinson’s disease. Part 1 was on ALS, MS and Huntington’s Disease. Part 3 in this series on neurodegenerative diseases will be on “Dementia”, more specifically Alzheimer's Disease.

PD is often thought to be caused by a loss of dopamine-producing neurons in the basal ganglia and substantia nigra. As such it is often treated with “dopamine boosting” approaches such as with the use of levapoda. However, there is far more to the story than simply the dopamine hypothesis. Furthermore, there are superior treatments available compared to levodopa, which has many negatives such as the fact that it often stops working, and causes adverse effects.

First, PD seems to often start with intestinal issues such as constipation. There have been cases where PD symptoms have improved when approaches were taken to alleviate the constipation with certain laxatives and purgatives.

“The doctor cleared his bowels with purgatives and gave him a grain of opium daily, and "in three or four days the shaking had nearly left him." Parkinson commented: "By pursuing this plan, the medicine proving a vermifuge, he could soon walk, and was restored to perfect health." -Ray Peat, Ph.D

I will write an article on chronic constipation sometime in the future, however, I have mentioned this topic in many of my articles already. Essentially, good bowel movements require enough energy production. Bowel movements should occur after every meal, so 3 meals a day means 3 bowel movements a day - to be optimal. All the processes of digestion require that there be enough energy production. For example, for the body to produce enough digestive enzymes, stomach acid, optimal gut motility and so on requires that the metabolic rate be at such a level where enough energy is being produced. A common symptom of hypothyroidism is constipation. Thus one approach to preventing, or treating, chronic constipation would be to do things to increase one’s energy state. I discussed this topic in two of my previous articles where I referred to the “Paradoxically Low Energy State”. These articles are the ones on Insomnia and ADHD.

Other than improving the metabolic rate to address slow gut motility and constipation, certain safe laxatives can be utilized to help rectify the issue. Ray Peat often discussed the use of well-aged cascara sagrada for this. Cascara contains a beneficial compound called emodin, and aloe vera contains a similar compound called aloe-emodin. As such, in addition to cascara, someone can consume aloe vera “juice” or aloe vera gel to help with constipation.

Another cause of constipation, and general gut dysbiosis, would be bacterial overgrowth and the resulting endotoxin, also called lipopolysaccharide “LPS”. The relevance of endotoxin is, that it can react with toll-like receptors such as TLR4 which can cause systemic inflammation. Endotoxin has been linked to many chronic health conditions, including virtually all neurodegenerative diseases such as PD. As such, approaches that lower endotoxin or that block TLR4 seem to be able to help. This is likely why minocycline seems to be so beneficial for many neurodegenerative diseases such as PD. Minocycline is an antibiotic, however, at low doses, (such as sub 50mg a day) it’s less of an antibiotic and more of a potent anti-inflammatory. Minocycline has been used for many other health conditions, including severe acne, and autoimmune conditions. Find out more on my articles on Acne and Autoimmune Disorders. Ray Peat even mentioned how minocycline could be useful for PD.

PD is not all about dopamine. Excessive glutamate, nitric oxide (“NO”) and acetylcholine all seem to play a role in the pathology. For instance, the anti-glutamatergic, anti-cholinergic drug amantadine is used for PD. Amantadine seems to be a very useful and relatively safe medication. It’s utilized (often off-label, but not always) for many neurodegenerative, autoimmune, psychiatric and behavioural disorders. For example, it’s utilized for PD, MS, HD, ODD, ADHD, OCD and certain autoimmune conditions. It is also an antiviral and used to be widely used to prevent and treat influenza type A, aka the flu. For more information on how to deal with high glutamate, refer to my first substack article which was “The Dance of Glutamate and GABA”. Also, Ray Peat mentioned the use of amantadine for various diseases and disorders, including PD.

“When it was discovered that the production of dopamine was reduced by the death of cells in the brain stem, L-dopa was introduced as the main drug treatment, since it can temporarily increase the amount of dopamine in the brain. The "dopamine theory" of the disease has become a sort of framework for thinking about the brain, such that other drugs that are helpful for Parkinson's disease have come to be defined as dopaminergic drugs, though their benefit might involve other systems, such as inhibiting serotonergic (Maj, et al., 1977) or cholinergic or glutamatergic nerves (amantadine or memantine).
“Despite its toxicity, L-DOPA continues to be the main medical treatment for Parkinson's disease, though the more appropriate drugs bromocriptine, amantadine, and memantine are also widely used. “
-Ray Peat, Ph.D

Eicosanoids seem to be involved in the neurodegenerative diseases. The two main eicosanoids are leukotrienes which are made via the lipoxygenase enzyme (“LOX”) and prostaglandins made by the cyclooxygenase enzyme (“COX”). Furthermore, phospholipase enzymes, such as PLA2 increase the production of eicosanoids as well. As such, lowering the activity of COX, LOX and PLA2 all seem to be able to help with PD. In addition to that, helping to block the effects of leukotrienes and prostaglandins also seems to be useful. I discuss this in detail in my article on asthma “Wheeze No More”, because LOX, PLA2 and leukotrienes all play a large role in asthma and COPD. There are many approaches one can take to lower these eicosanoids. For example, many herbs block PLA2, LOX and COX to some degree. Pycnogenol (pine bark extract), Boswellia Serrata, Gingko Biloba and Clove (eugenol) all seem to be useful here.

Aspirin is a COX inhibitor, among many other things, and as such may be useful for PD. Ray Peat certainly seemed to think so, and would often discuss the many benefits of aspirin, even writing an article on aspirin. Vitamin E is also useful for combating the overproduction of eicosanoids, especially if it contains policosanols. Edible beeswax is also a source of policosinols.

Interestingly enough, coffee and caffeine seem to be beneficial in combating these neurodegenerative diseases including PD.
Caffeine and Parkinson’s Disease: Multiple Benefits and Emerging Mechanisms
The neuroprotective effects of caffeine in neurodegenerative diseases
Also, there is some evidence that nicotine can be protective against PD. The most beneficial way to utilize nicotine in this context is likely via occasional use of a low-dosed nicotine patch, or perhaps a low-dosed use of nicotine gum. I doubt other forms of utilizing nicotine will be a net-positive.
Tobacco, coffee, and Parkinson's disease

Men in their 50s and 60s are usually the ones that start to develop PD. There seems to be a clear hormonal aspect of PD, and in my opinion, there are good arguments suggesting that lower androgens in aging men can make one susceptible to PD. Lower levels of testosterone and DHT seem to exacerbate PD and increasing these androgens seems to be therapeutic. A good general approach to maintain the androgen levels in men would be to make sure one consumes enough vitamin A and has enough active thyroid hormone, T3. Furthermore, low cholesterol levels should be avoided, and statins seem to worsen neurodegenerative diseases. Vitamin A, LDL cholesterol and the active thyroid hormone, T3, are all needed to produce the steroid hormones. Inadequate steroid hormone production will lead to less testosterone production, as testosterone is a steroid hormone. Supplementing pregnenolone and low-dose DHEA may be useful for those with PD.

“The first signs of the disease are usually noticed in middle age, as the reproductive hormones are declining. Men with Parkinson's disease have been found to be deficient in testosterone, one of the hormones involved in tissue maintenance and repair, and supplements of the hormone relieve some of the symptoms. Men's testosterone declines with stress and aging, and its conversion to estrogen is increased by stress and inflammation. Endotoxin specifically increases the conversion of testosterone to estrogen (Christeff, et al., 1992).” -Ray Peat, Ph.D

Drop in androgen levels causes Parkinson Disease (PD), DHT reverses it

It seems that PD is also a disease that involves impaired energy production. This is likely part of the reason why certain B vitamins such as vitamin B1 and vitamin B3 (niacinamide etc.) have been shown to drastically improve the pathology of PD in certain individuals. One reason why niacinamide seems to be able to help is because it can help increase NAD levels, and it can help increase the NAD/NADH ratio. Other things that can increase NAD and the NAD/NADH ratio would be electron acceptors such as vitamin K2 (menaquinone), COQ10 (ubiquinone), MB (methylene blue) and many other substances, such as compounds found in Pau d’arco tea. Vitamin B1 (thiamine) is very important as it is a crucial nutrient for the enzyme pyruvate dehydrogenase (“PDH”). Magnesium is also important for PDH. Thus, supplementing with higher doses of thiamine, magnesium, niacinamide and certain other substances can possibly be very therapeutic for PD. I discuss this topic in detail in my article on “How to Utilize Glucose Well”. There are some people with PD who have written books about how thiamine has helped them, I’d suggest reading these if you are interested in the thiamine and PD connection. Some with PD will likely benefit from IVs of thiamine, and fat-soluble forms of thiamine like allithiamine.

Speaking of energy production, red light therapy has been shown to be able to help with PD. One thing red light does is, it prevents NO (nitric oxide) from blocking cytochrome C oxidase in the electron transport chain. As such, by preventing this blockage, red light can help keep energy production at an optimal level. Red light therapy has been shown to be useful for a plethora of disorders, and utilizing it for PD sounds like a very good idea to me.

Red light therapy for Parkinson Disease (PD) begins human trials

More on the aforementioned dopamine loss hypothesis of PD, some consider this to be erroneous and that PD is actually a situation of excess serotonin and less of a situation of low dopamine. Part of the reasoning here is that many of the “dopamine agonist” drugs that help with PD, such as the ergot derivates (bromocriptine, lisuride etc.) are also serotonin antagonists. Regardless of which theory is correct, or rather “more correct”, it appears that these ergot derivate medications like bromocriptine and lisuride are a far better choice than levodopa. As mentioned earlier, amantadine and memantine are also good medication options. All of these would need to be prescribed by a doctor, but they are commonly used for PD so it shouldn’t be a problem. If this is the case, then serotonin “boosting” approaches such as the use of SSRIs would probably be a terrible idea for those with PD.

Relevant Haidut Blogposts:

The loss of dopamine-producing neurons and as such the resulting lower levels of dopamine are still likely a large part of PD, regardless of other causes and contributors. As such, certain anti-prolactin approaches may be useful, as prolactin is a major antagonist of dopamine in the body. Vitamin B6, zinc and vitamin E are known to decrease prolactin. Furthermore, eugenol, which is found in clove and some other natural products, is shown to help with PD via some dopamine-protecting mechanisms. Eugenol is generally neuroprotective.

Another nutritional supplement that seems to be very helpful for PD is lithium orotate. This form of lithium is different than the pharmaceutical lithium carbonate which is used for bipolar disorder. In the book “Nutritional Lithium, a Cinderella Story” Psychiatrist Dr. James Greenblatt devoted a whole chapter to how lithium can benefit those with PD. Lithium has many beneficial effects, such as decreasing PUFA in the brain (so there will be fewer eicosanoids as a result), it increases brain-derived neurotrophic factor (“BDNF”) and tyrosine hydroxylase (which is an enzyme involved in dopamine production) and it helps decrease ammonia. There are many other benefits of lithium, but overall it seems to be protective against PD. I’d highly suggest purchasing the lithium book referred to earlier in this section, it’s a fantastic book and very informative.

Vitamin D is also potentially beneficial for PD. Also, it seems that melatonin is possibly helpful for this condition as well. Taurine and Vitamin C are also promising supplements for PD.

Iron and manganese excess or “overload” can also potentially worsen PD or lead to PD-like symptoms. For a detailed discussion on these topics, I suggest checking out the information that Chris Masterjohn Ph.D. has provided on his substack. I highly recommend his page. Lactoferrin is a useful supplement here.

Check out

Stuff Your Doctor Should Know

’s podcast episode “Maintain Your Brain” where I was a guest along with Georgi Dinkov.

Stuff Your Doctor Should Know

Maintain Your Brain w/Georgi Dinkov & Constantine Kanargelidis

What a great way to start off 2023 with the brilliant Georgi Dinkov and my special guest Constantine Kanargelidis. It's a power packed episode about how to prevent cognitive decline with but not limited to: Limiting excess fat in the blood Increase utilization of glucose in the brain…

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2 years ago · 1 like · Stuff Your Doctor Should Know

Summary list of potentially beneficial substances for PD:

Agmatine
Niacinamide
Thiamine
Coffee, Caffeine
Lithium Orotate
Magnesium
Red light therapy
Vitamin D
Vitamin B6, zinc, vitamin E
Clove, eugenol
Cascara Sagrada, aloe vera juice/gel
Gingko Biloba, Pycnogenol
Taurine
Vitamin C
Aspirin
Melatonin
Lactoferrin
Nicotine (patch etc.)
Pregnenolone, DHEA, thyroid hormones (T3 and T4, or NDT etc.)
Potentially the use of supplemental androgens such as testosterone
Beneficial prescription medications
1. Minocycline
2. Amantadine
3. Memantine
4. Ergot derivatives: bromocriptine, lisuride etc.

Refer a friend

*None of this is medical advice. I am not a medical professional, always talk to your doctor*

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