Lead and Homocysteine Levels in a Series of Individuals Diagnosed with Parkinson’s Disease
I recently saw a patient who had been diagnosed with idiopathic Parkinson’s disease (PD) in 2000 when she was just 39 years old. Her history was compelling in that everyone in her family was well –no neurological diseases, parents hearty and healthy at 80 — and she herself was a healthy child. However, she has a daughter with autism.
It turns out this woman and her husband renovated a lead-saturated 100-year-old Chicago house over the course of 10 years — in the 1990s. She gave birth to her daughter-who was later diagnosed with the neurological condition autism–while in the house in 1998, around the time she first noticed a tremor.
When urine toxic metals were recently assessed in this patient, her lead (Pb) level was extremely high. In fact, it was eleven times the cut-off limit (her result was 22ug/24 hours; the cut-off limit is 2ug/24h hours). This finding suggests that she has a significant, long-time body burden of lead. Yes, lead toxicity is a contributing cause of PD and has been implicated in autism. In PD, lead has been shown to directly damage dopaminergic neurons and contribute to CNS oxidative stress. (In autism, the issue seems to be, in addition to CNS oxidative damage, compromised removal (biotransformation) of lead due to lesions in glutathione conjugation and methylation- more on that below.) There are currently about one million individuals diagnosed with PD in the US; as with most neurological diseases, its numbers are rising rather rapidly. Diagnosis is made only after the disease shows up clinically—that is, after 60-80% of dopaminergic neurons in the substantia nigra are lost. There are no great biomarkers to conclusively identify disease before this late stage, BUT, if we think about it from a functional/systems medicine perspective, early clues abound. There is no smoking gun genetic mutation in PD. Yes, there are some genetic mutations that increase risk, (here’s a recent free full text published by PLOS genetics and written by 23 & Me), but having a PD-associated mutation and developing PD isn’t a slam dunk. It’s now well accepted that Parkinson’s Disease, like most complex, chronic conditions is largely caused by chronic environmental exposures, including pesticides, herbicides, toxic metals and the like. Understanding the toxic connection, it becomes urgent that we regularly evaluate toxin exposures in our patients by taking a careful environmental exposure history and using appropriate labs- such as urine and/or blood toxic metals. When we find concerns, we need to address them immediately by removing the exposure sources and treating the patient, ideally BEFORE they develop clinically apparent complications such as PD.
Data mining in Parkinson’s disease
When I was completing postdoctoral training at a clinical laboratory, we conducted an informal “data mining” project, looking at nutrient imbalances and the presence of toxins in individuals diagnosed with Parkinson’s disease. I was struck by consistent patterns of imbalances. For instance, of the 32 individuals diagnosed with PD who had metals tested, over 60% had higher-than-average to very high lead levels. Additionally, 12 people had higher mercury and 11 had higher aluminum levels.
Of the 10 individuals with PD who had homocysteine levels assessed, all were on the higher side, ranging from 8.7 to 22.6. Six of the 10 individuals with PD had frankly elevated homocysteine. By comparison, a control group of six adults not diagnosed with PD, the homocysteine range was a much lower 5.4 to 9.3.
Incidentally, the highest homocysteine level (22.4) was in the same individual who had the highest lead level.
Methylation and sulfuration: I know you know it by heart…
There are a few ways to think about these data
- – Homocysteine is a marker of methylation activity. When it’s high (or low- as can be seen in autism), methylation is compromised. Methylation is involved in-among other myriad things- removing toxic metals from the body.
- – Methylation and sulfuration (think glutathione production) are very interrelated- see how homocysteine is the link between the two pathways in the figure above I borrowed from the net.
- – When methylation is inhibited–suggested by a HIGH or LOW homocysteine– sulfuration is compromised, too. This means a multitude of toxins aren’t being removed sufficiently AND antioxidant capability in the body is compromised. Double whammy.
- – No surprise: elevated homocysteine is seen in lead toxicity. Somewhat surprising: L-Dopa- the main therapy in PD– also results in homocysteine elevation. This is because COMT, the enzyme that metabolizes L-dopa, requires the methyl donor cofactor s-adenosylmethionine (see the figure above). L-dopa therapy depletes methylation causing a spike in homocysteine. We can infer that L-dopa therapy may hinder removal of the very toxins that contributed to the PD in the first place.
BUT….We certainly cannot take PD patients off L-dopa. It’s a critical treatment given the damaged dopaminergic neurons.
Our focus must be around carefully supporting normal methylation/sulfuration in this population. Anyone practicing functional medicine knows the drill: folate, B12, betaine and glutathione or the glutathione precursor n-acetylcysteine.
The dance for us as clinicians in treating the individual with PD is to normalize/assist in the removal of toxins by addressing methylation and sulfuration, but not boost methylation so aggressively that we promote excess metabolism of L-dopa. (When PD patients are given the COMT cofactor s-adenosylmethionine, it worsens symptoms.) It is therefore imperative that we monitor homocysteine, toxin levels and clinical symptoms when implementing this approach. Make sense?
Understand that while addressing methylation/sulfuration in the PD population is an essential component to a functional/systems approach, it’s only one area in a much larger systems approach. And as with autism, the earlier we start, the better the outcome. Ideally, we’re preventing the disease by getting there before it starts…….
A little more on lead…
Living in an old house is the most common cause of lead exposure in the US. And it’s not just renovating an old house. Just generating airborne lead-ladened paint particles from opening and closing windows is a huge exposure source, and inhalation is the most efficient route of lead absorption. But GI absorption is significant as well. Crops grown in lead-exposed soil (think soil saturated with leaded gas) bioaccumulate the toxin. We can use the bioaccumulation phenomenon to remediate soil, but just don’t eat those plants!
We can also find lead in common household items- such as the ceramics we eat on- especially those made in China. I recommend patients purchase at-home lead test kits for testing. I like 3M Lead Check sticks. Get them at Amazon.
A patient recently emailed this: A positive finding for lead on a ceramic dinner plate.
Blood lead cut-off levels have been lowered and lowered over time. This is a figure borrowed from the CDC. See Lead, No Safe Exposure Levels.