Excess iron in the brain is thought to be a contributing factor to PD and is known to damage the brain. Iron increases in the brain with age, but even more so in PD. Symptoms of too much iron in the brain include progressive dystonia (a movement disorder resulting in muscular spasms, twisting, and repetitive movements) spasticity, parkinsonism (slurred or slow speech, stiffness of the muscles, slow movement, and visible tremors), inability to coordinate movements (ataxia), neuropsychiatric abnormalities (confusion, disorientation, seizures, stupor, dementia), and eye problems, such as optic atrophy or retinal degeneration. Cerebellar atrophy is common in many cases as discussed in the following article :
rarediseases.info.nih.gov/d...
Here is a relevant quote from the article :
' Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia. Symptoms include progressive dystonia (a movement disorder resulting in muscular spasms, twisting, and repetitive movements) spasticity, parkinsonism (slurred or slow speech, stiffness of the muscles, slow movement, and visible tremors), inability to coordinate movements (ataxia), neuropsychiatric abnormalities (confusion, disorientation, seizures, stupor, dementia), and eye problems, such as optic atrophy or retinal degeneration. Cerebellar atrophy is common in many cases. '
The following meta analysis illustrates that iron levels are higher in the brain of PwP :
ncbi.nlm.nih.gov/pmc/articl...
Here is a relevant quote :
' Our analysis provides an overview of iron deposition in multiple brain regions of PD patients, and a comparison of outcomes from different methods detecting levels of iron. '
So while excess iron in the brain is problematic in PD and other neurodegenerative diseases, it is not yet known if removing excess iron from the brain will help alleviate symptoms caused by excess iron, except in animals where it has already been proven. MJFF is helping to fund an investigation of a drug that can remove excess iron in the brain as discussed here :
michaeljfox.org/grant/evalu...
This investigation was funded in 2021, but the above link does not say if the investigation has completed and if so, what were the results. If the investigation is not yet complete it should be completed soon. This investigation is to determine whether the drug is eligible for a clinical trial in patients. So if this investigation suggests that a clinical trial in PwP is warranted, it will still be many years away in terms of use of the studied drug by PwP.
Since it is already known that excess iron in the brain is detrimental to the brain and PD, it might be worth considering supplements that have shown the potential to remove iron from the brain or reduce the damage caused by iron overload or both. On that note, three supplements that come to mind are Melatonin, Thiamine and Hesperidin (MTH).
Melatonin
In this first study melatonin is shown to have protective effects against the damage caused by iron overload :
sciencedirect.com/science/a...
Here are some relevant quotes :
' Iron overload as a high risk factor, can be found in almost all human chronic and common diseases. Iron chelators are often used to treat iron overload; however, patient adherence to these chelators is poor due to obvious side effects and other disadvantages. Numerous studies have shown that melatonin has a high iron chelation ability and direct free radical scavenging activity, and can inhibit the lipid peroxidation process caused by iron overload. Therefore, melatonin may become potential complementary therapy for iron overload-related disorders due to its iron chelating and antioxidant activities. '
It is worth noting here that melatonin not only readily crosses the blood brain barrier (BBB), but melatonin and its metabolites have shown the ability to repair a derelict BBB.
' Numerous clinical and animal studies have demonstrated the use of melatonin to prevent or treat a variety of iron overload-related disorders, including neurodegenerative disorders (Wang, 2009), cardiovascular diseases (Tengattini et al., 2008), liver diseases (Zhang et al., 2017), ischemia–reperfusion organ injury (Sener et al., 2002, Cervantes et al., 2008, Zhou et al., 2018), diabetes (Peschke et al., 2015), osteoporosis (Li et al., 2019), cancer (Jung and Ahmad, 2006), etc. '
It is already well known that melatonin helps alleviate the damage caused by iron overload in the brain via its potent radical scavenging, antioxidant activities and anti inflammatory effects, but this next study shows that melatonin also increases Hepcidin, which works to maintain iron homeostasis in multiple areas of the body including the brain :
Here is a relevant quote :
' These findings reveal a previously unrecognized role of melatonin in the circadian regulation of hepcidin expression and iron homeostasis.'
Thiamine
Previously I have pointed out that an important method of action of thiamine in reducing PD symptoms and other diseases with elevated levels of the inflammatory mediator IL-17, is that thiamine significantly reduces IL-17 levels. Here is a link to that :
healthunlocked.com/cure-par...
Another important feature of thiamine in PD is that it also helps protect and maintain the blood brain barrier (BBB) from damage. A damaged BBB allows accumulation of iron and iron overload, which is bad for the brain, PD and AD. So this is likely another important benefit of thiamine for PwP and could partially explain why some people seem to take significantly longer to see benefit from B1. Perhaps benefit is delayed or limited until the BBB integrity is restored. It might also partially explain why some people after taking B1 for 6 months to 18 months suddenly have a worsening of symptoms that requires a downward B1 dose adjustment perhaps because once the BBB integrity is restored, less B1 is needed to maintain the benefit.
ncbi.nlm.nih.gov/pmc/articl....
Here is a relevant quote :
' Thiamine deficiency impairs the integrity of the blood‐brain barrier, thereby enabling iron to pass through and accumulate in the brain. '
Hesperidin
The following study explains how hesperidin, through multiple mechanisms of action protects against damage caused by heavy metals such as iron, while also crossing the BBB :
sciencedirect.com/science/a...
Here is a relevant quote :
' Hesperidin (HSD) and hesperitin (HST) are flavonoids from citrus fruits, and systematic investigations suggest their potential to combat the molecular alterations and toxicities induced by THMs. They mitigate heavy metal toxicity via antioxidant, anti-inflammatory, and anti-apoptotic effects via scavenging free radicals and modulation of ATPases, cell cycle proteins, and various cellular signaling pathways, including Nrf2/HO-1/ARE, PI3K/mTOR/Akt, MAPK/caspase-3/Bax/Bcl-2, iNOS/NF-κB/TNF-α/COX-2. '
In this next study it is suggested that hesperidin crosses the BBB and chelates excess iron from the brain :
ncbi.nlm.nih.gov/pmc/articl....
Here is a relevant quote :
' According to our results, hesperidin, and coumarin, as two natural compounds, have a high potential in iron chelating. Correspondingly, these compounds cross the blood-brain barrier and chelate excess iron in brain tissue. '
While the results of the MJFF funded investigation into the iron chelating drug that can cross the blood brain barrier is not available yet, it should be soon since the investigation was funded in 2021.
Once again, melatonin shows another good reason why PwP should consider it as an adjunctive treatment beyond the abundance of reasons I have previously given.
While MTH seem like three safe choices for dealing with iron overload in the brain based on their established safety profiles, but they are not alone when it comes to dealing with iron overload in the brain. A few others that have shown potential in this area are :
R- Alpha Lipoic Acid (R-ALA)
Curcumin
Quercetin
Berberine
Milk Thistle / Silymarin
Astaxanthin
Conclusion
Iron overload in the brain is detrimental to PwP and everyone else. It can cause symptoms similar to PD and can also be protected against via MTH chelation and protective mechanisms of action that can ameliorate the damaging effects of excess iron in the brain. Depleted thiamine in the brain damages the blood brain barrier (BBB) and that action allows the accumulation of iron in the brain which is damaging to the brain. The three supplements mentioned above, MTH, can work against iron overload in the brain and other critical areas of the body and all three cross the BBB. Other supplements mentioned above can also have iron chelating activities and or help to alleviate the damage caused by iron overload.
Art
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