FUNCTIONAL MECHANISMS & NUTRITIONAL REGULATION OF TOXIC METALS 101 “Compounds in competition”

It’s long been known in the scientific community going back decades that nutritional adequacy has a marked influence on the absorption, retention, toxicity, and excretion of toxic metals.

From the mucosal surfaces of the nasal passages down to the lining of the alveoli in the lungs, the body has an array of protective defences at its disposal in various forms that include mucus, cilia, macrophages, commensal microflora, and detoxification enzymes, to deal with toxins and foreign bodies.

In addition to the potential access points above – oral ingestion of toxins is a major route of entry to the body. The mucosal lining, pH of the gut, epithelial tight junctions, pancreatic enzymes, gut-associated lymphoid tissue (GALT), detoxification enzymes and peristalsis all work together to help reduce entry of pathogens or toxins into the body from the gut. A healthy functioning gut has the capacity to protect the body by limiting the absorption of chemicals, meaning less long term systemic exposure, and a lower toxic burden.

Once the toxic material has gained entry/access to the body – the portal blood supply to the liver is the next major step in dealing with the absorbed substances in the blood. Blood travels through hepatocyte lined passages known as sinusoids, where Kupffer cell macrophages help to filter out the microorganisms such as bacteria and other potential allergens. The portal vein delivers the toxins that have been absorbed through the gut, directly to the liver to be metabolically disarmed. It it’s at this point that the cycles of detoxification are fired up to metabolise the toxic material although fat soluble toxins will first enter the lymphatic system.

It’s not just exogenous toxins (originating outside the body) that our detoxification systems have to deal with. Endogenous sources of toxins (originating from within the body) from hundreds of metabolic processes that produce waste products such as the potentially toxic hormone metabolites, inflammatory mediators, and toxic bi-products produced by bacterial also impact the metabolic reserve required to run the detoxification pathways.

Metallothionein’s (MT) assist in this process by performing multiple functions, which include the detoxification of metals. These cysteine-rich proteins function as storage units for zinc and copper within the cell due to them having a high affinity for these two nutrients. The issue is that MT’s have an even greater affinity for the toxic metals cadmium of mercury.

The MT’s can preferentially bind cadmium and mercury, displacing zinc and copper. This cleaving and transfer of toxic metals across the cell membrane and has a protective effect, as accumulation of such metals within the cell would promote oxidative damage, producing free radicals that destroy the cells & tissues of the body. Metallothionein’s are synthesised in the presence of free zinc (Zn), copper (Cu), selenium (Se), as well as the amino acids histidine and cysteine. MT production is dependent on availability of the aforementioned dietary minerals, meaning from a clinical perspective that low, deficient or insufficient levels of any of the above reduce MT synthesis – especially Zn.

Detoxification capacity is determined by both the environment, our degree of exposure to toxins, and the endogenous production and removal of toxins. Clinical expressions of ill-health depend on a combination of the toxic load and the individuals capacity to effectively detoxify. Understanding this dynamic requires some knowledge of the ways in which common toxins interact with nutrients, in terms of inhibiting both nutrient function and biochemical pathways.

For example: the absorption of highly toxic heavy metals such as lead, as well as cadmium, is increased in states of iron or calcium deficiency. Individuals who have an inability to metabolise nutrients, such as the above are also at risk meaning this doesn’t begin & end at dietary intake – this also includes errors in digestion, absorption, assimilation, utilisation, & metabolism which has exactly the same net result in that they are unavailable.

In addition, metabolic issues with the utilisation of iron, or in a deficiency situation; is one of many factors that can lead to increased intestinal permeability where the cells of the intestinal wall become ineffective at vetting what should, and should not cross over into the bloodstream. This particular mechanism markedly enhances the uptake of aluminium (Al), an abundant dietary constituent that is not well absorbed through an intact enteric mucosa (the body’s first line immune defence that lines the various vulnerable entry points to the body, such as the intestinal tract, respiratory tract, nasal passages etc.)

As well as Al being a disruptor of mitochondrial function by blocking an important step in the citric acid cycle, which then goes on to effect the final step in energy production known as ‘oxidative respiration’ where the lion-share of ATP production occurs; aluminium has also been clinically associated with neurological disorders such as Alzheimer’s disease & dementia. Another example of nutritional interventions to manage toxic metals; Aluminium absorption can be decreased by magnesium (Mg), because Mg competes with aluminium absorption, not only at the main site of nutrient absorption – the small intestine, but also at the blood-brain barrier (BBB). The only caveat is that this relationship, like a number of others work both ways. In this particular example – If there is a high & chronic stress load, physiological damage or weakness in one or more of the body systems, and If Mg is low; Al gets the green light to stroll casually through what’s left of the mucosal membrane, and then go on to take a tour of the brain & the cells of the mitochondria, with an open invitation to stay as long as it likes buried in the cellular grey matter, or the organelles of the mitochondria, interfering with important functional metabolic processes & causing degeneration of the cellular tissues.

Considering a large number of the worlds population are deficient in Mg as well as other nutrients, due to poor diets, GI dysfunction, missing co-factors, excessive levels of daily stress signals, and a high metabolic demand due to high toxic loads – you can see how easy it is for various toxic metals to infiltrate & acclimate in the tissues of our bodies – and this is just one example of many.

The absorption of several other toxic metals may is enhanced by increased intestinal permeability which I tend to see a lot in Functional Medicine (FM) practice. Inadequacy of certain minerals also leads to enhance retention of toxic metals. Another example is a deficiency of Se and/or Zn increases mercury retention.

As described previously, toxic metals compete with, and can lead to displacement of nutrient minerals from protein binding sites, as well as excessive loss of minerals from the body. Therefore, the requirement for several nutrient minerals may rise significantly, way above the recommended daily allowance (RDA) in the metal toxic patient. This is where targeted therapeutic dosing (In excess of physiological quantities) may come into play over physiological dosing that tends to mimic natural production/quantities).

The excretion of toxic metals is governed by a complex change of interwoven activities. If any link in this chain is broken, proper elimination of toxic metals may not occur. Toxic metals must be released from the cell and moved from the extracellular fluid into the blood, transported from the blood to the liver or kidney, and then transported from the kidneys to the urine or the liver into the bile. Once the metal is in the bile, it must then be transported out of the body in the store before being reabsorbed back into circulation.

The very first step in mercury (Hg) excretion involves binding of the Hg to MT or glutathione (GSH) within the cell. MT production, in turn, is highly inducible through exercise and supplementation with Zn, where is it deficiency results in MT depletion. MT production is also induced by supplementary L-Cysteine or by brief periods of oxidative stress (as occurs from aerobic exercise). MT works in cooperation with GSH in the initial mobilisation of mercury from the cells, and it also shares intracellular antioxidant activity with GSH.

MT is actually 50 x times more potent than the bodies ‘master antioxidant’ glutathione with Se also playing an important role in binding to mercury within the cell informing the transportable complex. Therefore, Se supplementation can be useful in the treatment of Hg toxicity. Once matter is mobilised by MT, it is transported through the cell membrane by way of exocytosis. Hg must then be carried away from the cell to limit toxicity/structural damage to the cell membrane and to be transported to the liver. Exercise can be helpful in exhilarating the movement of mercury from the extracellular fluid, through the lymph and into the blood. Once mercury reaches the liver, it usually undergoes conjugation with GSH and is transformed into a mercapturate. The mercury mercapturate is then released into the bile for excretion.

Both the liver and kidneys are highly sensitive to GSH depletion by Hg. Hepatic and renal GSH production can be enhanced with nutrition & by supplementing the diet with Cysteine, NAC, GSH, ALA, cruciferous vegetables, dietary fibre, undenatured whey protein, onions and garlic.

Another pathological effect of Hg is on the microbiota. Hg can reduce numbers of beneficial flora when it comes into contact with the friendly microbes. I’ve seen a number of Hg toxic patients over the years who were Hg toxic, and has little to no growth of key strains of microflora that are essential for our functional health & wellbeing.

One of a number of FM combination strategies that i sometimes use with patients who are Hg toxic is by using lipoic acid at therapeutic doses. This can assist the removal mechanism by directly binding inorganic mercury in the liver, accelerating it’s excretion into the bile, while simultaneously inducing the formation of GSH. I’d like to stress that i never is implement unless a full comprehensive FM assessment is carried out at the very start, and in the majority of cases – added in after several months of restoring structure & functional integrity. ALA, as well as other compounds I often use in combination can be very powerful at inducing the detoxification process and should only be don’t under the care & guidance of an experienced FM practitioner who knows how to navigate & functionally support the patient through the process.

Any detoxification strategy, or induction in the wrong hands can make someone’s condition worse, and has the potential to poison the patient if they don’t have fully functional body systems to facilitate the safe excretion.

Once mercury has entered the intestines through the release of bile, it must leave the body via the stool. Optimal gastrointestinal function is vital, as well as adequate bile flow to prevent any recycling of Hg through enterohepatic circulation. Many people stir up Hg in body that goes on to get dumped into the GI tract, and then reabsorbed as they cannot effectively excrete it – making them feel horrible as a result. I have written about this in more detail in some of my other previous articles.

Fibre has a significant effect in lowering the total-body burden of Hg through sequestration of intestinal mercury and reduction in transit time. Other factors that I always consider in functional medicine are increased intestinal cell permeability (Leaky gut) and intestinal dysbiosis in the small intestine that result in deconjugating bacterial enzymes that disassemble the bound oxidised toxins, allowing them to be reabsorbed. Just a few key factors that determine how efficiently Hg can leave the body once it’s passed from the liver into the small intestine.

Because around 90% of excreted Hg leaves the body through the enteric route, colonic elimination is a vital component in maintaining an unbroken inefficient chain of excretion from the cell to the outside of the body… this goes for mercury, as well as a host of other toxicants.

Special care needs to be taken with any kind or induction of detoxification by chronically ill patients whose health is affected by toxicologic stresses. It is these individuals that do not have the physiological resiliency, or metabolic reserve to handle the elimination process of toxic metals once induced by nutrient therapy. Getting ones functional ducks organised in a neat row is essential before an induced heavy metal detoxification process be initiated.

This is why working with a highly skilled Functional Medicine expert is key, so they can carry out a full comprehensive assessment to know the persons limits, weaknesses & dysfunctions to design a functional wellness restoration plan that is bespoke for exactly where there body is at. If you are ready to work with an FM expert to help restore functional wellness, and get you feeling better – feel free to book a free 30 minute consultation with myself to see if we are the right fit to work together.

Thank you for your attention.

*By Steve Hawes