Early Research of Eliminating Microplastics from the Body

 

First Evidence of Microplastic Mobilization in a Human Subject – A Self-Experiment

A few months ago, I was shocked to learn that I most likely have about a plastic spoon’s worth of plastic in my brain. You do too. Not in one piece, but spread throughout the organ, as tiny micro- and nanoparticles trapped within and between your cells.

And it isn’t just your brain. Microplastics are present nearly everywhere researchers look. They are present in your liver, your kidneys, and in your blood. And they are ubiquitous in the environment. They have infested the ocean, our soils, other animals, and even plants.

When you eat an apple, you ingest millions of microplastic particles. Drink bottled water? You are ingesting more than 100,000 particles per liter. They are entering your body through your nasal mucosa and through your lungs every day, simply by breathing.

This is new information, enabled by sensitive detection methods that weren’t available just a few years ago. And we are only starting to grasp the health consequences. In animal and cell models, internalization of these particles invariably leads to cellular dysfunction and inflammation. In observational studies, microplastic burden strongly correlates with negative health outcomes – brains with dementia have more microplastics than healthy ones, and people with detectable microplastics in their arteries are more than twice as likely to have a heart attack or stroke, or to die of any cause than people without.

Once these particles enter our bodies, there is little we can do to remove them. Reducing exposure to new particles is the best we can do—at least, according to most experts. But my self-experiments suggest otherwise.

 

A Novel Approach for Microplastics Elimination

First, some necessary background.

When microplastics enter systemic circulation they can meet a number of fates. The smallest class of particles, less than about 10 microns (μm) in diameter, can penetrate deeply into tissues, taking up residence either between or within cells. This is where they presumably cause the most problems, interrupting cell and organ function, driving inflammation, and accelerating aging-related processes.

Immune cells like macrophages can also engulf these small particles quite efficiently through a process called phagocytosis, the same one that they use to clear cellular debris or pathogens. Other cells use a similar process called endocytosis. Once engulfed, the materials are sent to the lysosome, where the cells try to break them down with acids and enzymes.

Even small particles like this (<10 μm, yellow arrows) take up a massive volume within immune cells like macrophages:

Unlike natural substrates, cells aren’t able to digest the microplastics. Instead, the particles remain within the cells, driving an aberrant inflammatory state. The lysosomes, now full of plastic, can’t perform their normal function of turning over wastes. The cells stop doing their jobs and instead release cytokines that can damage neighboring cells, causing local tissue damage and irritation.

We don’t know the exact consequences of this process yet, but we know that disrupting lysosomal function more broadly is terrible for health, even driving severe lysosomal storage disorders that result in disability and death.

Fortunately, some of these small particles are also cleared by the kidney or liver and eliminated via urine or feces (in bile), respectively, a far more desirable fate.

Larger particles, in the 10-70 μm range or even greater, aren’t transported deeply into tissues with the same efficiency, although they can still be cleared via urine, a somewhat surprising finding. Some may also be cleared through bile, but just as with smaller particles, immune cells recognize many of these particles and try to engulf them. For some of the smaller particles in this range, the immune cells succeed, although the engulfed particle is almost the size of the cell itself—you can imagine the cellular damage that this causes. For the larger particles, the cells need another strategy.

When macrophages encounter very large debris, multiple cells can actually fuse together, forming a giant cell that can then engulf the target. These cells can comfortably engulf plastic debris at least up to 40 μm, but still can’t digest it once in the lysosome. When they fill up with plastics, they will have all of the same problems as with smaller cells and particles. They will become dysfunctional inflammation machines.

For a cell biologist, this is scary stuff. But, understanding this biology can help us formulate a strategy for clearance.

Thankfully, digestion isn’t the only way for materials to leave the lysosome. Cells have evolved a coordinated lysosomal stress response that can push lysosomes to dump their contents outside of the cell (a process called exocytosis), where particles have another chance to be eliminated. And we can activate this pathway with drugs.

 

Sulforaphane Boosts Lysosomal Exocytosis

Sulforaphane is an incredibly interesting compound. Derived from broccoli, it is, at the most basic level, a potent cell stressor. It is highly reactive, permanently attaching itself to proteins within cells. Left unchecked, this could disrupt all sorts of cellular processes. But, as you might imagine, evolution has found ways to protect against this.

Several proteins are exquisitely sensitive to stress from compounds like sulforaphane. These proteins essentially act as oxidative stress sensors, and when they are activated, they kick off a coordinated stress response, stimulating the cell to make more antioxidant proteins, more lysosomes, and more machinery for autophagy (the process that delivers many materials to the lysosome for degradation). This also causes cells to push lysosomes toward exocytosis, dumping their contents into the extracellular space for clearance. This can help to remove the offending toxin, clear proteins damaged by it, and restore a healthy cellular environment.

The antioxidant side of this stress response is driven by a protein called NRF2, and NRF2 activation is what you typically hear about with sulforaphane—hence the use as a booster of antioxidant and detox pathways. The lysosomal side is driven by a protein called TFEB; activation of this pathway by sulforaphane is a newer finding and is only starting to be widely appreciated. Other drugs can also activate TFEB, but sulforaphane seems to do it quite potently and effectively. It is also widely available as a highly pure supplement, and has a well-documented track record of safety in humans, making it an appealing candidate for therapeutic intervention.

A few weeks ago, a groundbreaking study reported the use of sulforaphane to treat a mouse model of Niemann-Pick disease Type C, a rare pediatric disease caused by the accumulation of cholesterol and fats within the lysosome. Normally, this accumulation leads to the widespread death and dysfunction of neurons. But when treated with sulforaphane, the mice dumped the excess materials from their lysosomes into the extracellular space, where it could be cleared away. This spared neurons from death and improved the health of the mice.

 

For the full article click here.