Inflammaging: Toxic Elements and Neurodegeneration

By George Gillson MD PhD CCFP

The posts this month are going to deal with two topics related to what is referred to as Inflammaging. To delve into this subject, I first need to explain a few things about inflammation. Inflammation is signified by pain, redness and swelling. It can flare up, burn hot and subside rapidly (acute inflammation) or it can be lower grade, long-lasting and smoldering (chronic inflammation).

Inflammation is also classified according to cause: sterile or non-sterile.  Sterile or non-infectious inflammation is caused by exposure to irritants and toxins (e.g. toxic environmental chemicals and chemical elements, food antigens, trauma).  Non-sterile Inflammation is caused by infectious agents including bacteria, viruses, parasites, yeasts and other fungi.

Chronic, low-level, non-sterile inflammation that is widespread (systemic) in the aging individual is called Inflammaging. One reason that this name was invented was so that people could create yet another tidal wave of books, many of them at least 2/3 full of recipes. Another reason is that Inflammaging captures various processes unique to aging, illustrated in the following diagrams.

In youth, cells are damaged by a variety of mechanisms and are often repaired successfully. If not, they die or become dormant. Either way, the immune system cleans up these cells. The ability of the youthful immune system to houseclean is heavily influenced by the various colonies of microorganisms (mostly bacteria) that peacefully coexist in our gums, nasal passages, upper airways, colon, skin and so forth.

As we age, these microfloral colonies change their characteristics in a way that modifies the immune system, hampering or blocking its ability to remove senescent/dead cells but increasing the production of inflammatory mediators/cytokines.  This “immunosenescence” results in accumulation of cellular debris/zombie cells and chronic, low-level inflammation. Et voila: Inflammaging!

There’s more to it than the simple explanation I just trotted out but researchers are now aware that inflammation and aging are basically inseparable: uncontrolled chronic inflammation leads to increased frailty and the acceleration of chronic illnesses such as diabetes, cardiovascular disease, osteoporosis, loss of muscle mass and cognitive impairment. These chronic illnesses fuel more inflammation which adversely feeds back on the immune system:

(Image taken from Franceschi 2018)

Much about Inflammaging has to do with ongoing (high) sugar content in our diets, changes in the overall mix of foods we eat as we age, changes in the gut mucosal barrier and changes in our ability to absorb key nutrients from the foods we DO manage to eat. I’ll talk about this more in the second post later this month. In this post I want to talk about the role that toxic chemical elements play in one of the most devastating aspects of Inflammaging: degenerative neurologic conditions such as Alzheimer’s Dementia (AD), Parkinson’s Disease (PD) and Amyotrophic Lateral Sclerosis (ALS).

A Short Chemistry Lesson

Chemical elements are the materials made up of just one type of atom.  Most pure elements are metals or metalloids, with a few gases and one liquid thrown in for good measure. Some of them are very toxic, especially the ones made of heavier atoms like cadmium, lead and mercury. Other elements made of lighter atoms such as arsenic, aluminum and manganese are also overtly or potentially toxic. Nevertheless, people refer to all the toxic elements as “heavy metals.” This gets on my last nerve since aluminum is pretty darned light, coming in at atomic number 13. Do me a favor and just call them “toxic elements”. I’ve circled some of the worst offenders on the feature image.

P.S. Minerals are combinations of atoms such as iron, chromium, oxygen, sulfur, phosphorus, and nitrogen: often they are crystals. People, probably the same people mentioned in the previous paragraph, always talk about supplementing with “trace minerals” but I don’t see anybody gnawing on crystals. “People” really should say they are supplementing with trace elements. Not that I’m anal or anything.

Anyway, many of the metallic elements are double-edged swords.  No pun intended. Although metal atoms like iron, zinc, magnesium, molybdenum, manganese and cobalt are essential to life, being cofactors for various enzymes, even these lighter atoms can be toxic if present in excess. The dose makes the poison, as the saying goes. But generally, it’s the heavier atoms that cause the most trouble.

They do so in a variety of ways: displacing useful cofactor atoms from enzymes, thereby inhibiting the enzymes: binding irreversibly to scavenger cellular housecleaning molecules such as glutathione and metallothionine: impersonating hormone molecules such as estradiol (E2) and binding to the E2 receptors: binding irreversibly to other important molecules such as proteins and DNA, thereby changing their shape and function: generating reactive free radical molecules.

The brain appears to be particularly sensitive to the negative effects of toxic elements. These toxins can trigger a firestorm of neurotransmitters known as “excitotoxicity,” impair the ability of the cellular powerplants or mitochondria to generate ATP energy , generate reactive free radicals as mentioned above and foster the accumulation of misfolded proteins. According to researcher Dr. Baoman Li:

“Excessive accumulation of metallic elements, such as arsenic (As), manganese (Mn), mercury (Hg), lead (Pb), aluminium (Al), nickel (Ni), bismuth (Bi), cadmium (Cd), zinc (Zn), copper (Cu) and iron (Fe), are known to be neurotoxic and increase the risk for neurodegenerative diseases, particularly of Alzheimer’s disease (AD) and Parkinson’s disease (PD).” (Li 2021)

Aging can contribute to neurotoxicity through bone loss with attendant release of stored lead. Those of us who grew up in the leaded-gas era carry lead in our bones, which can then released in later years as we lose bone mass through osteoporosis.

Is potential neurotoxicity due to toxic element exposure only an issue for workers in places like lead battery factories, ore smelters and waste-recycling plants? Sadly, the answer is “No.” Burning of coal for power creates fine particulates loaded with heavier toxic elements. These particulates can cross oceans, settling thousands of miles away and contaminating food and water. Well water has been implicated in the development of Parkinson’s disease without regard to burning of coal. Pigments used in toy manufacturing can contain toxic elements. Glazes and pigments for pottery and paints can also contain toxic elements. E-cigarettes and regular cigarettes can be an exposure vector for cadmium and other toxic elements. You don’t have to try very hard to be exposed to toxic elements on a regular basis.

Although exposure to a large amount of a toxic element can trigger acute neurotoxicity, neurotoxicity associated with aging most often arises from an inability to clear the relatively small amounts of toxic elements we are all exposed to in everyday life. Many of us can deal with this level of exposure without harm; however, toxic levels can build up very slowly in the wrong people. (Maybe not the people who talk about heavy metals and trace minerals.) This includes folks who have genetic mutations of housecleaning proteins that impair the ability of the body to bind, sequester and ultimately jettison toxic elements from the body via stool, urine and sweat. Many people eat poorly over decades and don’t get adequate amounts of key nutrients important for sequestration and detox.

So what can we do about all this?

First, minimize exposure through food and water.  Drink filtered water or reverse osmosis water that has had beneficial trace elements added back to it. Eat a wide variety of different nutrient-rich foods. Familiarize yourself with the foods that typically contain higher amounts of toxic elements and avoid them.  These foods include tuna (mercury), some brands of bone broth (lead), some brands of dark chocolate (cadmium) and certain types of rice (arsenic). Here are several sites that discuss potentially problematic foods in more detail: https://www.mindbodygreen.com/articles/food-sources-of-heavy-metals, https://www.eatthis.com/foods-heavy-metal-contamination/.

Proper hydration, saunas, exercise-induced sweating, massage and high fibre intake can all help to hasten elimination of toxic elements and prevent accumulation in our bodies. I mentioned lead accumulation in bone. Resistance training helps keep bone intact and prevents leaching of lead into circulation.

Testing of hair and urine for toxic element burdens is available through your Integrative/Functional Medicine practitioner, if you are concerned. A nutrition specialist can advise you on the best foods to eat to protect against neurotoxicity from chemical elements.

Sometimes food isn’t enough and supplementation of key trace elements such as zinc and selenium is needed. Other supplements important for protection against toxic elements include N-acetylcysteine or NAC, glutathione, Vitamin C, peat extract (yes you read that correctly) and modified citrus pectin. There are various herbs that support elimination of toxic elements in feces. Lastly, dimercaptosuccinic acid (DMSA) is an oral prescription medication which can bind and slowly eliminate toxic elements from the body via urine. Intravenous chelation can also remove toxic elements but that is beyond the scope of this post.

Conclusion

Inflammaging is driven by changes in the function  of the various cells in the immune system. Immune function is heavily regulated by the gut microfloral community, which changes with age. Degenerative neurologic diseases are one manifestation of Inflammaging and can be driven by accumulation of toxic chemical elements in tandem with immunosenescence. (The impact of accumulation of toxic organic molecules such as pesticides and fungal toxins is a whole other kettle of fish which will probably be discussed at some point but not today!)

There is much you can do to ameliorate or prevent the negative effects of Inflammaging and toxic elements on neurologic function. This is best done by partnering with your Integrative Functional Medicine team of practitioners to get the best advice on testing, dietary and other lifestyle changes along with appropriate supplementation of trace minerals (Oops!!) and other supplements.

Just as Tolkien said, “Not all who wander are lost,” I want you to remember that not all toxic elements are heavy.

Have a great month and be on the alert for the second post coming in a couple of weeks, which will deal with Inflammaging and chronic pain.

References

Afridi HI, Kazi TG, Talpur FN et al. Interaction between essential elements selenium and zinc with cadmium and mercury in samples from hypertensive patients. Biol Trace Elem Res. 2014 Aug;160(2):185-96. doi: 10.1007/s12011-014-0048-y. Epub 2014 Jun 25. PMID: 24962640.

Ash PEA, Dhawan U, Boudeau S et al. Heavy Metal Neurotoxicants Induce ALS-Linked TDP-43 Pathology. Toxicol Sci. 2019 Jan 1;167(1):105-115. doi: 10.1093/toxsci/kfy267. PMID: 30371865; PMCID: PMC6317426.

Baarz BR, Rink L. Rebalancing the unbalanced aged immune system – A special focus on zinc. Ageing Res Rev. 2022 Feb;74:101541. doi: 10.1016/j.arr.2021.101541. Epub 2021 Dec 13. PMID: 34915196.

Eggersdorfer M, Berger MM, Calder PC et al. Perspective: Role of Micronutrients and Omega-3 Long-Chain Polyunsaturated Fatty Acids for Immune Outcomes of Relevance to Infections in Older Adults-A Narrative Review and Call for Action. Adv Nutr. 2022 Oct 2;13(5):1415-1430. doi: 10.1093/advances/nmac058. PMID: 35587877; PMCID: PMC9384096.

Franceschi C, Garagnani P, Parini P et al. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018 Oct;14(10):576-590. doi: 10.1038/s41574-018-0059-4. PMID: 30046148.

Li B, Xia M, Zorec R, Parpura V, Verkhratsky A. Astrocytes in heavy metal neurotoxicity and neurodegeneration. Brain Res. 2021 Feb 1;1752:147234. doi: 10.1016/j.brainres.2020.147234. Epub 2021 Jan 5. PMID: 33412145; PMCID: PMC8999909.

Miller AL. Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity. Altern Med Rev. 1998 Jun;3(3):199-207. PMID: 9630737.