QUATS going on?!?

BE WARNED: THIS POST MIGHT UPSET SOME READERS A recently published research report has caused a bit of a fuss in the media, and I have been contacted by a lot of concerned readers regarding this particular study. It deals with some chemicals – which can be found in everyday products – that may be having a negative effect on biological processes that are related to Parkinson’s disease – specifically, the normal functioning of the mitochondria (the power stations of each cell). In today’s post we will discuss the new research, what the chemicals do, and whether the Parkinson’s community should be concerned.

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Source: Sacramentodentistry

Toothpaste.

It is something that most of us take completely for granted in the modern world. A product that sits in our bathroom, by the sink or on a shelf, and 2-3 times per day we stick some of it in our mouth and brush it around a bit. Given the well ingrained habit of repetitively ingesting of the stuff, we have little trouble with the idea of switching brands or trying new variations (“Oooh look, this one will make your teeth whiter. Let’s try it”).

I mean, come on – it’s just toothpaste. It’s safe, right?

It probably won’t surprise many of you to learn that the composition of toothpaste has changed quite a bit over the years, but what might amaze you is just how many years are involved with that statement: 

Egyptian toothbrush. Source: Nathanpaarth

The Egyptians recognised the importance of looking after one’s teeth at a very early stage. Apparently they had a lot of trouble with their teeth because their bread had grit in it which wore away their enamel. As far back as 5000BC, they had a form of toothpaste that they used to clean their teeth. It was a mix of powdered ashes of ox hooves, myrrh, powdered and burnt eggshells, and pumice (Source: Wikipedia). The Greeks, followed by the Romans, improved on the recipes (by adding abrasive ingredients such as crushed bones and oyster shells – delightful, huh?), but it wasn’t until after World War I that the modern day pre-mixed toothpastes became popular.

The cavity fighting chemical, Fluoride, was first added to toothpastes in the 1890s, and in 1908 Newell Sill Jenkins (an American dentist) invented the first toothpaste that contained disinfectants. It was called Kolynos (from the Greek words Kolyo nosos (κωλύω νόσος), meaning “disease prevention”). 

Source: Flickr

Following the advent of Kolynos, most toothpaste companies added antiseptic and disinfectant agents to improve the quality and effectiveness of their product. Being offered a tooth cleaning product with magical antibiotic properties seemed to reassure consumers that they were buying something that might actually work. And this led to more and more chemicals being added to toothpaste. Such additions included chemical like triclosan, cetylpyridinium chloride and benzalkonium chloride.

These chemicals are safe though…right?

Weeeell, more recently there has been a lot of analysis looking into the biological activities of some of these chemicals. With newer technology, better systems of testing, and more advanced understanding of the biology, it now appears that some of the chemicals we previously believed were safe miiiiight actually have a few mildly negative properties.

And then there are other that have not-so-midly negative properties.

In fact, many of these chemicals have now been banned from being included in certain household products.

For example, on the 2nd September 2016, the Food and Drug Administration (FDA) announced that it was banning the use of 19 chemicals – such as the widely used triclosan – in soaps and body washes (Click here to read that announcement). That ban comes into effect this month (having given the consumer companies 12 months to prepare themselves). This move by the FDA came on the back of building evidence that chemicals like triclosan were having negative effects. For example, triclosan appears to effect hormones (Click here for more on this) and causes muscle weakness (Click here to read about that).

In this particular example, the ban on triclosan was widely welcomed by activists who had been calling for the change. But many also thought that the move didn’t go far enough. For example, the ban only dealt with ‘soaps and body washes’.

Which begs the obvious question: Why is triclosan still allowed in your toothpaste?

A common ingredient. Source: MNN

And understand that toothpaste is just the tip of the iceberg. Triclosan can be found in…. well, basically everything!

From deodorants to first aid products, from kitchen cutting boards to ice cream scoops, socks & underwear to ear plugs, yoga mats to lip gloss & moisurizers (Click here to read more on this). Like I said, everything.

In addition, while banning Triclosan in soap and hand washes, the FDA deferred a decision for one year on three additional ingredients used in consumer wash products – those being benzalkonium chloride, benzethonium chloride and chloroxylenol.

That one year period is basically up and we are now awaiting an announcement from the FDA.

Which makes the timing of a new research report rather curious (or perhaps advantageous).

What does the new research report say?

This is the new research report:

Title: In Vitro Evaluation of Mitochondrial Function and Estrogen Signaling in Cell Lines Exposed to the Antiseptic Cetylpyridinium Chloride
Authors: Datta S, He G, Tomilov A, Sahdeo S, Denison MS, Cortopassi G.
Journal: Environ Health Perspect; (2017) DOI:10.1289/EHP1404
PMID: N/A                   (This article is OPEN ACCESS if you would like to read it)

The researchers who conducted this study had previously performed two large experiments investigating the effect of 1,600 different chemicals (all sorts of stuff: antiseptics, additives, and drugs) on different aspects of mitochondrial functioning. Specifically, in one study they had looked at the effects of those chemicals on mitochondrial oxygen consumption (Click here to read that study) and in the other study they had also looked at ATP synthesis (Click here to read that study).

Hang on a second. What does all this mean? Mitochondrial oxygen consumption and ATP synthesis?

As we have mentioned a few times in previous posts, mitochondria (mitochondrion, singular; from the Greek words mitos (thread) and chondros (granule)) are tiny little bean-shaped structures within the cells in our body, and their primary function is to act as the power stations. They supply the bulk of energy that cells require to keep the lights on. Lots of mitochondria are required in each cell to help keep the cell alive (as is shown in the image below, which is showing just the mitochondria (in red) and the nucleus (in blue) of several cells).

Lots of mitochondria (red) inside cells (nucleus in blue). Source: Clonetech

Mitochondria produce a chemical form of energy which is called adenosine triphosphate (or ATP). ATP is absolutely critical to the normal functioning of a cell. Thus, any chemical or drug that messes with the production of ATP can be placed in our ‘bad stuff’ basket.

A critical ingredient in the production of ATP is oxygen. Mitochondria are HUGE consumers of oxygen. Disproportionately so in fact. If oxygen was shared out evenly within a cell, we would have serious problems. And all of the oxygen that is carried to the mitochondria is basically consumed by a single enzyme, called cytochrome oxidase, which is one of the last enzymes in the process that drives ATP production.

So any chemical or drug that messes with the mitochondrial oxygen consumption can also be placed in our ‘bad stuff’ basket.

Ok, and what did the researchers find?

Well, when they put all of the data from their two previous studies together they had a nasty surprise (of the ‘bad stuff’ basket variety).

In the graph below, you will see a horizontal and a vertical line. Around the lines are small circles, each representing a particular chemical. The location of the circle depends on how much the chemical scored on each test. For example, the horizontal line displays measures of ATP synthesis, while the vertical line represents oxygen consumption. Now, in either cases you do not want a negative score (-8.0 on the ATP synthesis line would mean that the chemical is having a really bad effect of ATP production, even if it has a positive score on oxygen consumption). And if you have a chemical with a negative score on both lines (which would put the small circle in the bottom left hand corner of this graft), well that would be really, really bad.

So imagine the horror of the investigators when they found that 6 of the worst performing compounds were all from just one family of chemicals that are commonly used as ingredients in common household products!

All of the black circles in the bottom left hand corner of the graph (indicating a poor score on both ATP synthesis and oxygen consumption) come from a family of chemicals called quaternary ammonium compounds (or QUATS).

What are QUATS?

Quaternary ammonium compounds are basically ammonium salts. Each QUAT has a central “core” characterised by a positively-charged nitrogen atom (N⁺). Given their particular chemical structure, they are widely used as disinfectants, surfactants, fabric softeners, and also anti-static agents (e.g. in shampoo). They are really useful chemicals.

Examples of QUATS. Source: Quats

The figure above displays two examples of QUATS:

1. Alkyldimethyl benzyl ammonium chlorides (or ADBAC in the image above) are widely used as ‘surfactants’ (or compounds that lower the surface tension between two liquids or between a liquid and a solid). ADBAC are used extensively to kill bacteria, fungi, and algae as part of deodorant, and disinfectant products.
2. Diakyl Dimethyl Ammonium Chloride (or DDAC in the figure above) are also used as antiseptics and disinfectants.

And there are many more.

But six of these QUATS were in the most mitochondrial-inhibiting group of chemicals in the graph above?

Exactly. And the worst performer of those six QUATS was cetylpyridinium chloride (or CPC), which is commonly used in brands of mouthwashes, toothpastes, lozenges, throat sprays, breath sprays, and nasal sprays.

And this finding was a bit of a problem, because as one of the investigators involved in the study Dr Gino Cortopassi (from the UC Davis School of Veterinary Medicine) said, “This raises concern because exposure to other mitochondrial-inhibiting drugs, such as rotenone and MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), is associated with increased risk for Parkinson’s disease.”

Rotenone and MPTP are two commonly used neurotoxins that specifically target the mitochondria.

Wow! Scary. What did the researchers do next?

Since they were using a human breast cancer cell to conduct the experiments, and knowing that normal mitochondrial activity is essential for the production of the sex hormone estrogen, the researchers turned their attention to estrogen production. They found that QUATS inhibited normal estrogen signaling in cells at the same concentrations that inhibited mitochondria.

The investigators concluded the study by suggesting more research of these troublesome QUATS is required. They also point out, however, that there are some QUATS that do not inhibit mitochondria, suggesting the need “to explore antimicrobial QUATS without anti-mitochondrial activity”.

Crikey! Is this the first time anyone has ever found anything like this?

Unfortunately, no.

There have been a couple other studies published recently that have looked at QUATS and what they might be doing inside the body. One of those studies reported observations made in an animal research facility:

Title: Exposure to common quaternary ammonium disinfectants decreases fertility in mice.
Authors: Melin VE, Potineni H, Hunt P, Griswold J, Siems B, Werre SR, Hrubec TC.
Journal: Reprod Toxicol. 2014 Dec;50:163-70.
PMID: 25483128                  (This article is OPEN ACCESS if you would like to read it)

The investigators who wrote this report noticed that when they moved to a new research facility in 2005 the rate of fertility in their female mice dropped from a normal level of 60-70% to just 10%. In addition, they saw an increase in the rate of prolonged or difficult deliveries in their female mice. They conducted a series of tests (changing aspects of the environment, etc) but none of these changes made a difference. It was only then that they realised that the housing of the mice was being cleaned with a particular family of chemicals.

Would you care to take a wild guess – a shot in the dark – as to what the name of that family of chemicals was?

In March 2006, the QUATS cleaning reagents were removed from the facility and replaced with a disinfectant containing sodium chlorite. Miraculously, as the remnants of QUATS disappeared, the fertility of the mice returned to normal.

In 2008, researchers at another lab on the opposite side of the USA began using disinfectants containing two QUATS: ADBAC and DDAC (which we mentioned above in the description of QUATS). This research group ALSO noticed a decline in breeding performance in their mouse colony following the introduction of these cleaning agents.

Being scientist, both research groups felt compelled to independently follow up these observations so they both gave daily QUAT treatment in mice and they found that while this treatment did not affect food consumption it did significantly reduce fertility and survival of the mice.

To read more about this particular episode, click here for a discussion in the journal Nature.

One of the research groups from that first observational study followed up their initial work with some more direct analysis of QUATS and last year they published this report:

Title: Quaternary ammonium disinfectants cause subfertility in mice by targeting both male and female reproductive processes.
Authors: Melin VE, Melin TE, Dessify BJ, Nguyen CT, Shea CS, Hrubec TC.
Journal: Reprod Toxicol. 2016 Jan;59:159-66.
PMID: 26582257                  (This article is OPEN ACCESS if you would like to read it)

In this study, mice were exposed to both ADBAC + DDAC in their food for two weeks, and the investigators found that fertility was affected in both females and males. In females, QUATS exposure resulted in fewer ovulations, fewer implantations and reduced frequency of cycles, while in males, ADBAC + DDAC exposure resulted in lower sperm counts and reduced sperm motility. Even low doses of the QUATS resulted in reduced sperm parameters in the males.

This same research group followed up this study with another report that was just recently published:

Title: Ambient and Dosed Exposure to Quaternary Ammonium Disinfectants Causes Neural TubeDefects in Rodents.
Authors: Hrubec TC, Melin VE, Shea CS, Ferguson EE, Garofola C, Repine CM, Chapman TW, Patel HR, Razvi RM, Sugrue JE, Potineni H, Magnin-Bissel G, Hunt PA.
Journal: Birth Defects Res. 2017 Aug 15;109(14):1166-1178.
PMID: 28618200                 (This article is OPEN ACCESS if you would like to read it)

The researchers found an increased rate of neural tube defects in both rats and mice exposed to ADBAC+DDAC. The neural tube is the developmental structure that gives rise to the brain and spinal cord. Shockingly, the neural tube defects persisted for two generations after exposure to the QUATS was stopped, and male exposure alone was enough to cause the neural tube defects.

Oh man, this is bad! All of my house hold products are full of these chemicals. Panic and run! Panic and run!

Yeah, this has been a common reaction to the general media news about this research. But before you do that – read on.

The Consumer Specialty Products Association (or CSPA) has responded to the first article with the six mitochondrial affecting QUATS, and in their response the CSPA state:

“Quats are well-understood, effective chemicals and many applications are registered by EPA. To register quats, EPA requires comprehensive testing to understand the toxicity, exposure and uses of the chemicals.  In addition, EPA requires a regular reevaluation of ingredients to incorporate any new information for every ingredient used in a disinfectant or sanitizer, including quats. As part of the most recent reevaluation, EPA reviewed an extensive database of scientific studies and has allowed their continued use in products that clean, sanitize and disinfect homes and institutions. The numerous studies conducted and used for EPA registration do not indicate long-term health or reproductive effects.

CSPA has serious concerns with how the study is being interpreted as it relates to potential effects on people. There are a number of complex studies that do not show the effects that were observed in the cell culture study. A positive result in a cell culture study indicates the need for further study in a more complex biological system that would be more predictive of adverse outcomes in people. Numerous studies support the conclusion that these compounds are not associated with developmental or reproductive effects in people. Consumers can be confident in their continued use of these products.”

(Click here to read the full statement)

In addition, the CSPA also responded to the study that found neural tube defects following QUATS exposure. In that statement, they wrote:

“Quats are well-understood, effective chemicals and must be registered by the U.S. Environmental Protection Agency (EPA). To register quats, EPA requires a comprehensive understanding of the toxicity, exposure and uses of the chemicals. In addition, EPA requires a regular reregistration of ingredients to incorporate any new information for every ingredient used in a disinfectant or sanitizer, including quats. As part of the most recent reregistration, EPA reviewed an extensive database of scientific studies and has allowed their continued use in products that clean, sanitize and disinfect homes and institutions. The numerous studies conducted and used for EPA registration do not indicate long-term health or reproductive effects. Quats do not bioaccumulate in the body, are rarely inhaled, and skin absorption is limited.”

EDITOR’S NOTE: Does this look suspiciously like a ‘cut and paste’ job to anybody else? Continuing on:

“Among the study’s major flaws are:

• The controls had effects. The control groups in the study showed toxicological effects in their offspring. In typical studies, control groups are not exposed to the chemical so scientists can measure the differences between the control groups and groups that are intentionally exposed to a chemical. This is how scientists know there are problems with the study when the control groups and exposed groups show similar effects.
• The study did not assess the level of exposure the rodents had to the ingredients in the room. The study refers to these levels as “ambient exposure” but there is no information defining or measuring “ambient exposure” for the purposes of the study.
• The chemistry of quats doesn’t allow them to be inhaled in appreciable amounts.
• The largest amounts tested that should have caused harmful effects did not. The results are inconsistent. In the study, the rodents were given excessive doses of quats orally that did not appear to produce noticeable toxicological outcomes. To put it in perspective, the amounts given to the rodents are equivalent to a 150-pound-person ingesting approximately 1.5 quarts of disinfectant daily for eight weeks. These high amounts are not possible when using household and institutional products properly and as intended.

These significant flaws are but a few of the many major problems with this study, which calls into question the conclusions made by the researchers.”

(Click here to read the full statement)

Who is the CSPA?

“The CSPA is the premier trade association representing the interests of companies engaged in the manufacture, formulation, distribution and sale of more than $100 billion annually in the U.S. of familiar consumer products that help household and institutional customers create cleaner and healthier environments. CSPA member companies employ hundreds of thousands of people globally” (Source).

So they are the house-hold products company’s representatives?

Exactly.

Now can I panic and run?

No.

While I’m not sure I would agree with everything the CSPA have stated, it is important for us to remember that all of these studies need to be replicated by independent research groups before we can confidently say that some QUATS are having negative effects. And note the word ‘some’ – in the first study described in this post, the investigators acknowledge that some QUATS are very useful. It would be wrong to stigmatise all QUATS and put them all into the ‘bad stuff’ basket because of a few bad apples.

In addition, we have all been using products with QUATS for the last 40-50 years, which makes me ask the question:

Has there been an increase in the rate of Parkinson’s disease over that time?

It is difficult to answer, but I don’t really think so. Not noticeably at least. The ratio is still hovering around the 1 in 500 people in the general population.

There is an often cited graph from the Centre for Disease Control which indicates a change in frequency of people dying with Parkinson’s disease. The graph suggests that there has been an increase since the 1980s (in the graph below the blue-green line near the bottom is Parkinson’s disease and it starts to rise from 1980 onwards):

Death rates associated with particular diseases. Source: CDC

This increase is more likely to be the result of better diagnosis and medical record keeping. The rate of people dying with Parkinson’s disease only began to rise in the 1980’s with the introduction of ICD-9 (International Classification of Diseases and Related Health Problems – a system for labelling diseases and causes of death), which introduced new criteria, as well as more flexibility in labelling alternative causes of death. The ICD system of coding death data was not adopted by the USA until 1968 and it took a long time implement (state by state). In addition, previous versions of the ICD (6, 7, & 8) had not changed much over the years. Then in the 1980s, suddenly more people were being labelled with Parkinson’s disease, but that rise has plateaued since 2000 and the introduction of ICD-10. This “better diagnosis and medical record keeping” idea shows itself particularly well in the death rates associated with Alzheimer’s disease (the grey line) – look at that scary rise from nothing in the 1980s!

Take home message: We must be really careful with how we interpret data.

But what can we do about the nasty chemicals in toothpaste?

Simple: Stop using the branded toothpaste.

Que?

If you are worried, simply stop using the commercially available toothpastes. There are actually a lot of ingredients in toothpaste that don’t really need to be there. For example, the wonder drug: fluoride. It is supposedly the ingredient that prevents cavities, but it doesn’t really do that job very well. Another one is Glycerin. This stuff is found in almost every toothpaste in the supermarket/pharmacy (even some of the natural toothpastes have it!). Glycerin gives toothpaste its pasty texture, and it also keeps it from drying out. It can, however, coat your teeth which can prevents them from remineralising.

There are lots of natural alternative options:

1. Salt water – dip your brush in it and do as normal.
2. Baking soda – dilute it in water and brush with the brine.
3. Coconut oil – it has anti-fungal and anti-bacterial properties help mouth cleaning.

There are also natural alternatives to shampoos and other house hold items that decades of advertising have brain washed us into thinking that we need.

What does it all mean?

A recent study has found that members of a family of chemicals that are commonly used in house hold products may be having a negative impact on mitochondrial processing. Given that a lot of research suggests that mitochondria are affected in Parkinson’s disease, naturally folks within the Parkinson’s community are concerned by these new results. Until the results are independently replicated, it is too soon to start panicking. People who are concerned, however, can take steps to limit their exposure to these chemicals as a precautionary step.

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Finally, on a personal note, last night (for the first time) I looked at the ingredients of the toothpaste that we’ve been using for a long time:

eek!!!

Did I brush my teeth after seeing this, you ask?

Of course I did – I am a creature of habit. And if the regulators say Triclosan is safe in toothpaste, then who am I to argue with them?

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The banner for today’s post was sourced from Btrworlds