I’d like to spend a bit of time elaborating on the effects of lead in a child’s body. I’ll skip the long-term effects of lead for the most part, because that story is more about adults than kids. This is simplified and taken from my posts in the “Kids with Lead Poisoning” Facebook group.

Part 1. Lead competes with calcium

Calcium has a whole lot of important functions in the body and lead interferes with them all, in a small or major way.

Calcium and lead use the same uptake mechanism in the gut. More calcium in the diet means a smaller percentage of lead gets absorbed.

Nervous system

Calcium channels are gatekeepers that let calcium move across the cell membrane and are involved in muscle contraction and nerve signalling between synapses by release of neurotransmitters. In this scenario, lead doesn’t just compete with calcium, it displaces it.

Tomas Guilarte describes lead as turning off the lights which represent synaptic communications.

In older kids it means their brains run a bit more slowly. In infants, the presence of lead reduces the brain’s ability to create the synaptic interconnections that are necessary for the development of intelligence. This is a semi-permanent effect because it is a developmental defect.

Please note that the biggest change in IQ happens at a blood lead level going from 0 tp 5 ug/dL.

The neurological effects in older children will generally revert to normal if the lead is removed. The cognitive deficit produced by lead in young infants can be reversed, BUT it needs more than just removing lead and I’ve posted about this.

There are a couple of points to make here. The first is that even relatively low (below 5ug.dL) blood lead levels still cause measurable neurological deficit so the only 100% safe level of lead in the blood is none. The second is if you can remove the lead in your child’s body, they will improve. That’s something you can do.

Bones

Nervous activity aside, lead gets deposited in bone, initially the trabecular or spongy bone near the joints and then in the cortical or hard bone between the joints. Lead in trabecular bone has a half-life of up to 1-3 years, in cortical bone it can be as long as 10-20 years. That’s a long time unless you hurry things up with chelation. Even that isn’t very fast because you can only grab lead released by remodelling, but it’s a lot faster. Vitamin D speeds up remodelling so it helps.

Lead in bone serves as a storage depot of lead in the body which can release lead back into the circulation when bone is remodelled. That can cause more harm. also If there’s enough lead in bone, the lead weakens the bone and can slow bone healing.

You can measure the amount of bone with x-ray fluorescence spectroscopy (XRF) if the test is available. If there’s enough lead there, it can be seen with a standard x-ray, and that was one of the ways to detect severe chronic lead poisoning a few decades ago.

There are some other effects but these are the important ones.

Part 2: Lead competes with Zinc

Zinc and lead compete for absorption in the gut so like the case for calcium, added zinc in the diet means lower lead absorption. That sounds like a lot more zinc would be a good idea, but it isn’t because too much zinc is toxic. Zinc rich foods are a much better idea than zinc supplements unless they’re only taken occasionally.

Lead displaces zinc from zinc enzymes which leads to inactivation. The most relevant example of this is delta-aminolevulinic acid dehydratase (ALAD) which when inhibited leads to the build-up of delta-aminolevulinic acid (ALA) in the circulation.

The other enzyme involved in porphyrin synthesis is ferrochetalase which inserts iron into the porphyrin molecule. It isn’t a zinc enzyme but is inhibited when lead binds to sulphydryl groups near the active site. This leads to the build-up of zinc protoporphyrin in the circulations. I repeat this has nothing to do with zinc, but like ALAD, it results in reduced haem synthesis and anaemia.

The result of inhibition of these two enzymes and and the resulting build-up of ALA and zinc protoporphyrin gave us the earliest biochemical tests for chronic lead exposure.

Another important role for zinc is that it provides the bridge between sulphydryl (sulphur) groups in proteins and enzymes, to allow the correct folding and conformation of zinc finger proteins, many of which are involved in DNA binding proteins and transcription enzymes.
That can lead to reduced gene repair and transcription and can lead to DNA and RNA errors. It can also prevent the binding of histones. The effect of lead on zinc-finger proteins is likely the reason for the much higher incidence of ovarian cancer in women with the BRCA1 gene in raised blood lead levels.

Note this is separate to the potential damaging effect of lead induced free radicals on DNA.

I forgot to point out that supplements like lipoic acid n-acetyl cysteine do a pretty good job of reducing the effects of lead when it comes to sulphur proteins

Part 3. Lead binds to Sulphur

Lead has a great affinity for sulphur. In the previous post I mentioned lead inhibiting ferrochetalase by binding to sulphydryl groups near the active site of the enzyme, and also that displacing zinc from zinc-finger proteins can have a major impact on DNA/RNA functions including gene control.

But the interaction of lead with sulphur has a lot more effects so I’ll try and cover what else is important.

Red Blood cells

When you are first exposed to lead it binds avidly to the haemoglobin and other proteins in red blood cells. At that stage up to 99% of circulating lead is in the red blood cells.
Haemoglobin isn’t considered to be a sulphur protein but it does have sulphydryl and amino acid group that form a chelate structure of sorts. Luckily it doesn’t affect the oxygen-carrying ability of haemoglobin.

When red blood cells are formed, they have a significant amount of delta-aminolevulinic acid dehydratase (ALAD). However this has no function in the red blood cell, being essentially a leftover, but it does bind lead. The functional ALAD that is inhibited by lead is found in the red marrow in spongy bones.

Red blood cells are a hugely simplified type of cell with no chromosomes and no mitochondria. That makes them particularly vulnerable to lead since it reduces cellular energy output by binding to sulfhyryl groups in enzymes involved in energy production. This energy reduction impairs functionality that maintains the cell membrane which results in increased fragility and obvious structural damage. Lead-containing red blood cells are smaller, more brittle and less able to deform as needed in small capillaries.

The Brain

The brain is somewhat unique as lead in the brain has a significantly higher half-life than other organs, excluding bone.
This involves much more than just lead-sulphur interaction but let’s concentrate on sulphur.

Lead binds most avidly in astrocytes and microglia. Astrocytes have a role in maintaining the blood brain barrier and microglia function in part as the brain’s immune cells, one of the things lead does is cause inflammation. It’s important to point out that lead-sulphur binding is only part of the reason lead is retained. Nevertheless leads binds tightly to protein sulphydryl groups and also the inner membranes of mitochondria.

In the treatment of encephalopathy, including a sulphur-based chelator with calcium disodium EDTA results in a better outcome. It has been claimed that EDTA doesn’t cross the blood brain barrier, but since EDTA has been found in cerebrospinal fluid that’s probably rubbish. Nevertheless sulphur compounds like lipoic acid and n-acetyl cysteine would likely help stripping lead out of the brain.

The Kidneys

Kidney proximal tubular cells can form nuclear inclusion bodies, lead complexes with sulphur proteins, which can alter renal gene expression and cause cell damage over time. There are also inflammatory effects but not due to sulphur binding.

4. Lead as an oxidizing agent

Lead is a powerful irritant and is responsible for free radical damage and the depletion of antioxidants in the body. It not only inhibits enzymes and other substances involved in antioxidant activity, it generates free radicals which can damage cell and mitochondrial membranes and DNA.

The kidneys are particularly prone to damage by lead due to the accumulation of lead sulphur aggregares in the proximal renal tubules and oxidative damage leading to inflammation and scarring. It was the observation of kidney disease and encephalopathy in children in Queensland, Australia in the early 1900s (where I live) that first established the health risks in children exposed to lead paint.

Long-term exposure to lead can lead to kidney problems in adult life, including kidney failure, reduced kidney function, hypertension and gout.

It’s fun to digress here and point out that saturnine gout in lead risk workers has been directly associated with lead exposure, and that the relatively high instance of gout in the past amongst wealthy people was most probably due to the use of lead acetate as a sweetener in wine, coupled with the use of lead crystal (up to 40% lead) glass and pewter (lead-tin alloy) goblets. That isn’t the only cause of gout but the association with lead exposure is significant.

Since I’ve strayed into talking about adults, I’ll continue the story.

Irritation by lead of epithelial lining cells in the arteries can result in calcification and atheromas (atherosclerotic plaques). That’s not the only cause of atherosclerosis, but it’s an important one. While non-calcific plaques also exist, if they contain calcium deposits, you can likely blame lead. When your calcium score is high, that’s arterial calcification, and the blockages are more likely due to lead exposure in the past than high cholesterol.

An analysis of a US National Health and Nutrition Examination Survey (NHANES 3 , over 14,000 adults, 1988-, 1992-2011) estimated that up to 412,000 more deaths from cardiovascular disease occurred in the US as participants blood lead increased from 1 ug/dL to 6.7 ug/dL.

Note that is well below the accepted maximum occupational blood lead levels (30 ug/dL). It’s probably small wonder lead risk workers die 5 years earlier on average. There are a range of estimates, but a conservative one suggests 20% of cardiovascular disease is associated with lead exposure.

There are a host of other diseases caused by lead and associated with ageing but the most prominent are neurological diseases. That includes a potential association with MS, ALS and dementia, not just cognitive deficits or increased violence.

Doctors ignoring non-toxic levels of lead in a child, and not treating them to remove all the lead, forget that lead exposure can have long-term consequences thanks to the long half-life of lead in the bones.

It needs to be mentioned that there are quite effective ways to reduce oxidative damage from lead, using vitamins C and E as well as many sulphur-containing anti-oxidants. Garlic doesn’t just keep vampires away. But the best way to deal with lead is to remove it, preferably quickly.

While I’m discussing anti-oxidants, an early use for EDTA (FDA approved in 1947) was as a food preservative, because once heavy metals like lead were bound to EDTA, they no longer generated free radicals that caused oils and fats to go rancid.
Hopefully you’d know if you’ve read more of my posts, that calcium disodium EDTA is also great for removing lead (and other heavy metals) from the body.

In summary, to the best of my knowledge lead provides absolutely no benefit to the body. Everything it does in the body is harmful.

We should never ignore the statement from the CDC that there is no safe level of lead in the body.

I guess I’d better mention the one scenario I know of where scientists in the early 1900s raised rats on a totally lead-free diet, and the rats became iron deficient. That was likely due to the composition of the diet so I’m pretty certain that the CDC is still right.