Apples, Arsenic, and Risk - Part 20: It is - and always will be - about the dose.

"All substances are poisons; there is none which is not a poison. The right dose differentiates a poison…." Paracelsus (1493-1541).

I hate to keep whipp'n that dead horse, but that's what is missing in these discussions on the arsenic that has been found in apple juice.  Let's look at what Russell H. Greenfield, MD says on the Dr. Oz website regarding arsenic in apple juice:

The 10 ppb level [arsenic MCL for drinking water] is simply as close as we can reasonably get considering our natural exposure to arsenic in the environment and other limitations. At that level, almost all experts agree our drinking water is quite safe.

Shouldn't the same goal or, at the very least, similar science-based exposure guidelines, be in place for the juices we commonly give to our children?

What goal would Dr. Greenfield want to see?  Consumer Reports thinks "the standard should be 3 ppb" and the FDA, on December 15, 2008, issued a memo on research they had done regarding arsenic in the juice:

In conclusion, the chronic consumption of apple juice products containing over 23 µg/L (ppb) inorganic arsenic would represent a potential health risk.

The FDA in 2008 says 23 ug/L is the maximum total arsenic in apple juice that would not pose a potential health risk.  That 23 ug/L is based on the actual dose a child would take in (uptake) based on how much apple juice is normally consumed.  That's the way it is supposed to be done, that's the way the FDA did it in 2008, so why does Consumer Reports, Dr. Oz, Dr. Greenfeild, and good ol' Chuck Norris think the FDA has dropped the ball on this?

Let's look at how the FDA came up with that:

Consumption estimates were based on average consumption over two days for individuals who consumed apple juice (eaters only) and were calculated for two population groups: Males and females (MF) from birth to 2 years of age and MF 2 years of age and older.  

The estimates included foods codes for products that were 100% apple juice, including infant apple juice; juice blends that included apple juice as an ingredient were not included.

Relying on results of the more recent 2003-04 NHANES, consumption of apple juice by MF birth to 2 years was estimated to be 16.7 and 36.2 g/kg body weight/day at the mean and 90th percentile, respectively, compared with previous estimates of consumption for all juices of 19.1 and 43.4 g/kg body weight/day.  

For MF 2+ years, consumption of apple juice was 6.0 and 12.9 g/kg body weight/day at the mean and 90th percentile, respectively, compared with the previous estimates for all juices of 6.0 and 13.0 g/kg body weight/day. 

Since consumption estimates from both surveys are similar, the level of concern (LOC) that was calculated for the previous assessment (23 ug/L, or ppb) can be applied in the case of apple juice. 

The 23 ug/L is for inorganic arsenic and is based on the dose a child would take in drinking apple juice.  The reason that number is higher than the 10 ug/L for arsenic in drinking water is that the dose from drinking water is estimated to be 20 ug at the 10 ug/L MCL.  This is because the MCL is based on drinking 2 liters of water per day.

What that means is this:

A 30 kg child (66 pounds) drinking 36.2 grams of apple juice per kilogram of body weight consumes 1086 grams of apple juice which is 1.1 liter.  That's the amount that will deliver the dose of arsenic.  That quantity of apple juice is the 90th percentile highest amount of apple juice estimated to be consumed.  A child drinking that much apple juice would receive 25.3 ug of total arsenic at a maximum FDA acceptable concentration of 23 ug/L.  The highest anticipated "daily dose" for this 30 kg child is 25.3 total arsenic from drinking apple juice.

For drinking water, that same child would consume 2 liters of water at the MCL of 10ug/L for a total daily dose of 20 ug.  That's what the EPA considers a safe dose.

So normal apple juice consumption will see less than 25.3 which is equivalent to what would be consumed if drinking two liters of water at the MCL for arsenic of 10 ug/L.

Drinking apple juice at a total arsenic concentration of less than 23 ug/L is the same as drinking water at the MCL 10 ug/L for arsenic.  The dose is based on the amount consumed per unit of fluid.  You drink less apple juice per day then water so apple juice can contain more ug/L of arsenic and still be considered safe.

Sounds counter intuitive, especially when you are talking about toxicity. We are concerned with the amount of the toxin - dose - received not the amount of the toxin found.  This is why you cannot compare the MCL for drinking water to the concentration of arsenic found in apple juice.  The MCL has been established for a dose based on consuming 2 liters per day.  You therefore need to compare the dose the receptor is anticipated to receive with the maximum dose - mg/kg body weight - established as "safe."

This is how it works.   It is - and always will be - about the dose when describing toxicity.

23 ug/L of total arsenic presents less dose than a drinking water MCL of 10 ug/L and is based on the assumptions of how much of each is consumed.  As long as the daily dose does not exceed 20 ug for a 70 kg person - or - 0.28 ug arsenic/kg body weight - we will not expect to see any short term or long term potential health risks over a 70 year lifetime!

That's why Dr. Greenfield states on the Dr. Oz website:

At that level [10 ug/L], almost all experts agree our drinking water is quite safe.

Even ol' Chuck Norris agrees with that, although I am pretty sure he has no idea that he does:

At the very least, the FDA should not allow more arsenic in apple juice than it allows in Americans' drinking water.

"Not so fast!" Yells our hero Chuck Norris, "tell them about the cover-up!"  No, Chuck, you tell them:

Tragically teetering on a huge U.S. health cover-up, the FDA posted eight "previously undisclosed test results" for apple juice samples from across the country that had arsenic levels that superseded even its own "level of concern" for inorganic arsenic. Two of those eight samples had an arsenic level of 27 ppb. One had a level of 42 ppb, and two others were at 45 ppb.

Tragically teetering?  Oh chuck, you are such the drama queen!  Here is what the FDA discloses in another memo dated November 21, 2011:

In July 2011, we issued an Import Bulletin to significantly increase the number of juice products sampled and analyzed for arsenic under the Toxic Elements program. Importantly, of the 74 samples collected as a result of this import bulletin, all were from China. Of these:

• 1 sample was above 23 ug/L total arsenic
• 1 sample was 10 ug/L total arsenic
• 2 samples were 11 ug/L total arsenic
• The remainder, (almost 95 percent), were below 10 ug/L total arsenic.

 Compare that to the arsenic levels reported by Consumer Reports.  But wait, there is more:

[we] now have a total of 160 apple juice samples collected from 2005 to 2011. These include 70 samples posted by FDA on September 27, 2011 and an additional eight samples that were part of this data set. These eight samples, which had not been previously posted, all have total arsenic levels greater than 23 ppb and were in the process of being further verified.

The data set also includes 82 new samples collected in the latter part of 2011 for which the data have just now become available. Of these 160 apple juice samples:

• Almost 88 percent had fewer than 10 ppb total arsenic
• 95 percent had total arsenic levels below 23 ppb total arsenic.

Okay...anything else from the lyin' stinkin' covern' up FDA?

Similarly, from the Total Diet Study program:

• Nearly 77 percent of the 134 composite apple juice samples tested from 1991 to 2009 (including baby food and general consumption samples) had total arsenic levels below 10 ppb.
• 95 percent had total arsenic levels below 23 ppb.

Cover-up?  C'mon Chuck, this ain't nothin' different than what Consumer Reports found.  How many samples do you need to have analyzed to get you to understand that we're not in any danger.  I mean, really Chuck?

Until then, tides of arsenic will continue to flow from foreign produce fields into American bloodstreams.

Tides of arsenic?  Chuck, Chuck, Chuck...

I have written 20 posts on this topic.  I have tried to show how many of these statements from Consumer Reports, Dr. Oz, and Chuck Norris are not substantiated.

As much as I believe we should consume food that is grown locally and with little to no pesticides, I cannot say that the reason for doing so is because foreign grown apple juice contains more arsenic than American. The Consumer Reports data shows that it does not.

I cannot support lowering the inorganic arsenic level to 3 ug/L.  There is no evidence to support that.  None.  Period.  The FDA's level of concern of 23 ug/L appears to be prudent, justified, and can be supported by the same data used to produce the drinking water MCL for arsenic at 10 ug/L.  And at that level, one more time courtesy of Dr. Greenfield:

"almost all experts agree our drinking water is quite safe."

It is - and always will be - about the dose received and not the amount detected.  You cannot compare the ug/L established for water with the ug/L found in apple juice.  This is no different than comparing a one pound ingot of lead with a one pound feather pillow.  They both weigh the same but one of them you would not want dropped on your head.

Let me sum it all up.  Here is how it works, it only works this way.

If little 2 year old Johnny weighs 66 pounds (30 kg) and he drinks the upper most amount of apple juice the FDA research found, 1.1 liters (36.2 g/kg body weight/day), and that apple juice contains the highest amount of total arsenic the FDA says is safe - 23 ug/L - he would consume 25.3 ug of total arsenic each day he drank 1.1 liters of apple juice.

That's a pretty big two year old and that's a lot of apple juice to drink, but that's a potential and I'm trying to force a "worst-case" scenario to illustrate my point.

25.3 ug for a 30 kg child comes out to 0.84 ug arsenic/kg body weight.  0.84 ug is 8.4E-4 mg/kg.

The IRIS reference dose (RfD) for inorganic arsenic is 3.0E-4 mg/kg-day.  Now before you say "whoa! That's more than double" remember this:

In general, the RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime.

Little Johnny will not drink more apple juice per body weight when he gets older, in fact, the FDA reports that after two years of age, a child drinks about half of that amount per body weight.  And as their body weight increase towards 70 kg, the dose of arsenic received per body weight gets less and less each day they consume apple juice.  So that at the end of 70 years, the dose of arsenic is around 3.0E-4 mg/kg-day based on a max of 23 ug/L.

Oh, and that worst-case amount of arsenic, 8.4E-4 mg/kg-day, is for total arsenic.  Looking at the Consumer Reports data, inorganic arsenic is about 30% less than that.

Nevertheless you may say, this worst case mega-heavy-baby little Johnny is consuming more than the IRIS RfD of 3.0E-4 mg/kg-day of inorganic arsenic based on these FDA estimates and calculations.

True that, but I have another little bit of information that will let me know everything will come out OK.  Even if little Johnny were to drink 1.1 liters of apple juice with 23 ug arsenic every day and never weigh more than 30 kg, the estimated dose of total arsenic - 8.4 mg/kg-day - is just barely above the NOAEL (No Observable Adverse Effect Level) of 8.0E-4 mg/kg-day listed by IRIS for inorganic arsenic and well below the LOAEL (Lowest Observable Adverse Effect Level) of 1.4E-2!

So is the FDA correct in identifying 23 ug/L arsenic in apple juice as a level of concern?  Yes.

Can the FDA substantiate their claim that:

...the chronic consumption of apple juice products containing over 23 µg/L (ppb) inorganic arsenic would represent a potential health risk.

Yes.

Is Dr. Russell H. Greenfield, MD correct when he says:

It remains very unlikely that you have done any harm to yourself or to your children through the drinking of apple juice. 

Yes.

Can you and your kids drink apple juice despite all of the misinformation and assumptions made by Consumer Reports, Dr. Oz, and Chuck Norris?

Yes.

Everything in moderation.

Now, how do you like them apples!


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Apples, Arsenic, and Risk - Part 19: Like Dysentery, Only Sweeter

Ubiquitous = Everywhere

Consumer Reports tells us:

Arsenic is a naturally occurring element that can contaminate groundwater used for drinking and irrigation in areas where it’s abundant, such as parts of New England, the Midwest, and the Southwest. (1)

If we water our apple trees with ground water that is naturally contaminated with arsenic, or groundwater that is contaminated with arsenic from past pesticide and industrial use, that arsenic will be sucked up the trees and end up in the apples they produce.

That's one way, the other way has a bit more of the yuck factor involved.

If you look at the NHAMES data Consumer Reports references, and focus on this statement they make in their report, you will maybe understand why it is "ubiquitous."

Because most ingested arsenic is excreted in urine, the best measure of recent exposure is a urine test. (1)

Perhaps I can make my point using a song from the play "The Book Of Mormon."  That song, "Joseph Smith American Moses" has lyrics that discuss the spread of dysentery.  Now if you are familiar with South Park, the guys who wrote this play are the same ones who write that, so if you have sensitive ears or eyes you may not want to go looking for them.

So with apologies to Stone and Parker, here are my lyrics to illustrate the ubiquitousness of Inorganic Arsenic.

Arsenic goes out in the urine

Urine goes down the sewer

The sewer ends up in the river

The river irrigates the apple tree

The apple tree makes the apple juice

The apple juice goes in the cup

The cup goes to the mouth

The mouth goes to the stomach

Arsenic goes out in the urine

So now that I have that little ditty out of the way, let me put it all together using Vinny Gambini: - from "My Cousine Vinny - as a way to further illustrate what may be happening.

I'll set the scene: Vinny is in court cross examining Russell H. Greenfield, MD who made this statement:

"...the US government put a stop to the use of inorganic arsenical pesticides years ago. The same action, however, has not been taken by other countries, such as China, which just so happens to be the major source of apple juice products found in American stores. Chinese farmers, including apple farmers, still may use pesticides containing arsenic." (1)

The courtroom audience is hush, the air thick...

Vinny Gambini: And where does apple juice come from?
Dr. Greenfield:  China
Vinny Gambini:  Good...but more specifically....
Dr. Greenfield:  From the apples that grow on apple treesVinny Gambini: And those trees...do they require anything other than sunlight and soil to grow?
Dr. Greenfield: They need water.
Vinny Gambini: Water, that's right, don't be afraid just shout 'em right out when you know 'em.  And where does that water come from?
Dr. Greenfield: The rain
Vinny Gambini:  Rain...that's right, is that all?
Dr. Greenfield: Groundwater
Vinny Gambini: Ahh...pumped up from below the surface.  Anywhere else?
Dr. Greenfield: Rivers...
Vinny Gambini: Yes, rivers, streams. pounds, lakes...tanks - as you call them in Texas.  You mean surface water?
Dr. Greenfield: Yeah...surface water
Vinny Gambini: And is the water pumped up from the ground always free of arsenic?
Dr. Greenfield: No
Vinny Gambini: And that urinary arsenic we've been talkin' about.  Anyway that can get into the surface water?
Dr. Greenfield: Yeah, if that's where the treated water is discharged.
Vinny Gambini: So, what do you think? Isn't it possible that the arsenic is naturally coming from the soil or is present in the surface or groundwater used to irrigate the apple trees and not just from pesticides?
Dr. Greenfield: I suppose.
Vinny Gambini: I'm finished with this guy. 

I (almost) rest my case.

Next (and finally the last) Post: Apples, Arsenic, and Risk - Part 20: It is, and always will be, about the dose.


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Apples, Arsenic, and Risk - Part 18: The China Syndrome

Russell H. Greenfield, MD writes:

Dr. Oz and his staff have performed their own investigation into this matter, and they, too, found high levels of arsenic in some apple juice products. The findings raise significant health concerns for us and for our children, and have generated incredulousness that this could happen in our country.

After everything I have read on this topic, a theme began to take shape. A theme that may help answer the question I asked in my last post: Where is the connection being missed by these well educated professionals?

Let's see if you can pick it out:

"...in our country."

"...the US government put a stop to the use of inorganic arsenical pesticides years ago. The same action, however, has not been taken by other countries, such as China, which just so happens to be the major source of apple juice products found in American stores. Chinese farmers, including apple farmers, still may use pesticides containing arsenic." (1)

"More and more food comes into our country from foreign soil each year, but the FDA is able to inspect only a small and woefully inadequate percentage of the products reaching our shores before they reach our store shelves and then our plates. Why? Because funding for the FDA is consistently on the chopping block in Washington, DC. It is this fact that merits our anger." (2)

"Also, request that they apply pressure to improve Chinese agricultural practices, both for our safety and their own population." (3)

"Look for the country of origin on your apple juice label. You’re likely much safer drinking a product that comes only from the United States." (3)

"Go organic when possible. Organic apple juice comes from apples that are, by definition, not treated with harsh pesticides." (3)

"For the past decade, most concentrate has come from China. Concerns have been raised about the possible continuing use of arsenical pesticides there, and several Chinese provinces that are primary apple-growing regions are known to have high arsenic concentrations in groundwater." (4)

"Currently there's an alert for increased surveillance of apple concentrate from China and six other countries "where we have a suspicion there may be high levels of arsenic in their products," says FDA spokeswoman Stephanie Yao. But in fiscal 2010, the agency conducted physical inspections of only 2 percent of imported food shipments." (4)

"The fact is that the U.S. is getting more and more of its fruits and vegetables from other countries, and many of them do not preclude or limit arsenic in their pesticides or even their water supplies as the U.S. does. Oz reported that apple concentrate comes from up to seven countries; 60 percent of it is imported from China alone." (5)

Notice somethin'?

What would a nerdy public health blogger do with that theme?  Hmmm, I wonder what was found in the samples collected and analyzed by Consumer Reports?  Let me be clear here, I am writing this BEFORE I have crunched the numbers.  My initial observation is that we will not see any difference in the amount of arsenic from country to country.  I hope so, because I have a really good song to use to make my point!

Okay, back.  Here is what I found (mean value):

Source: Consumer Reports

Interesting....

Looks like the apple juice from China has less inorganic arsenic than that from the USA.  I wonder what that means?  Well, here is what I think, lets look at these two statements:

"The fact is that the U.S. is getting more and more of its fruits and vegetables from other countries, and many of them do not preclude or limit arsenic in their pesticides or even their water supplies as the U.S. does. Oz reported that apple concentrate comes from up to seven countries; 60 percent of it is imported from China alone." (5)

"For the past decade, most concentrate has come from China. Concerns have been raised about the possible continuing use of arsenical pesticides there, and several Chinese provinces that are primary apple-growing regions are known to have high arsenic concentrations in groundwater." (4)

If arsenic pesticides are no longer used in the USA, and apple-growing regions of China have high arsenic concentrations  then we would expect the apple juice from China to have more arsenic than the USA, not less.  In fact, look at the concentrations Consumer Reports found.  I have ranked them from highest to lowest.

Source: Consumer Reports

You know the terrible thing about looking at the data that is reported?  It sometimes makes you have to admit that your assumptions have been wrong.  We assume that foreign apple juice is bad because they don't have our standards.  But when you look at theirs compared to ours, that's not what the data shows.

But the data does show something.  It shows that arsenic is in all apple juice and it looks like the country it comes from plays little into the concentration.  Which makes me wonder what that organic apple juice ol' Chuck Norris wants us to drink contains?

So if it's not arsenic pesticides putting the arsenic in our apple juice (if it is, and we don't use it, that does not bode well for us) where is it coming from?

Enter the word "ubiquitous."


Next Post: Apples, Arsenic, and Risk - Part 18: Like Dysentery, Only Sweeter.


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Apples, Arsenic, and Risk - Part 17: Generated Incredulousness

Remember this:

It remains very unlikely that you have done any harm to yourself or to your children through the drinking of apple juice. 

Russell H. Greenfield, MD, Clinical Assistant Professor of Medicine, UNC Chapel Hill School of Medicine makes that statement on the Dr. Oz "Taking Action: Arsenic and Our Children" web page. Dr. Greenfield is a medical doctor.  I only play one on TV or when I sleep at a Holiday Inn Express.

So, where to start,,,oh yeah, you know what really grinds my gears?...

Let me pose a series of questions here.  First off:

Should parents of apple juice drink'n kids be "incredulous?"

"The findings raise significant health concerns for us and for our children, and have generated incredulousness that this could happen in our country."

Should these parents be "concerned?"

"Should you be concerned? Yes."

Should these parents be "angry?":

"Should you be angry? Yes,"

Dr. Greenfield, MD, tells parents they should be incredulous, concerned, and angry.  Those are his comments on the Dr. Oz web page.

And if I asked Dr. Greenfield, MD, "why," he would most assuredly tell me - as he wrote - because:

"The findings raise significant health concerns for us and for our children."

And if I asked "what findings?" he would tell me:

Dr. Oz "found high levels of arsenic in some apple juice products."

So if high levels of arsenic in some apple juice products raise "raise significant health concerns for us and for our children," then it wouldn't make any sense to then tell us:

It remains very unlikely that you have done any harm to yourself or to your children through the drinking of apple juice.

You see if we have not "done any harm to yourself or to your children through the drinking of apple juice" then there is no "significant health concerns for us and for our children" to be raised.

Why is that?  Because the reason to be "incredulous," "concerned," and "angry" is because of the "significant health concerns" based on the "high levels of arsenic in some apple juice products."  Those same levels which Dr. Greenfield, MD, tells us "remains very unlikely that you have done any harm to yourself or to your children through the drinking of apple juice."

This is the same strange logic - or lack thereof - that Mike Judge was trying to make in his movie "Idiocracy:"

Secretary of Energy: "Yeah, it's got electrolytes."
Joe: "What are electrolytes? Do you even know?"
Secretary of State: "It's what they use to make Brawndo."
Joe: "Yeah, but why do they use them to make Brawndo?"
Secretary of Defense: "'Cause Brawndo's got electrolytes."

Or in this case...

Me: "So we should be be incredulous, concerned, and angry?"
Dr. Greenfield, MD: "Yeah, the apple juice has arsenic."
Me: "And the arsenic in the apple juice is harming us and our children?"
Dr. Greenfield, MD : "No, it remains very unlikely that you have done any harm to yourself or to your children."
Me: "So why should we be incredulous, concerned, and angry?"
Dr. Greenfield, MD : "'Cause the apple juice has arsenic."

I have written 16 posts - not including this one - trying to show how the amount of arsenic found in apple juice is no where near the health concern that Consumer Reports, Dr. Oz, and the rest of these MDs and PHds have been trying to make.

Now let me get this out there - once again - in case my posts are being construed as "pro-arsenic."  Less is better.  Less inorganic arsenic consumption is better.  Period.

That being said, the amount of arsenic found in the 85 apple juice samples tested by Consumer Reports does not:

"raise significant health concerns for us and for our children." (1)

"suggest that chronic exposure to arsenic even at levels below water standards can result in serious health problems." (2)

What is being reported by Consumer Reports and Dr. Oz concerning the arsenic they detected in the apple juice is missing one of the basic caveats of toxicology and risk assessment:

We assume that there is a "daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime." (3)

We call this "daily exposure" the the "oral Reference Dose" or "RfD" and it is based on the assumption that thresholds exist for certain toxic effects.  The RfD expressed in units of mg/kg-day and is an estimate (with uncertainty spanning perhaps an order of magnitude) of an acceptable daily dose.

When we are at - or below - the acceptable daily dose, we can say things like:

"It remains very unlikely that you have done any harm to yourself or to your children through the drinking of apple juice." 

The amount of arsenic that is acceptable in our drinking water is based on  RfD that has been established for arsenic.  It allows us to draw a line in the sand and state that at a level of 10 ug/L is the "daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime."

Dr. Greenfield, MD, seems to understand this, look at what he writes:

"The 10 ppb level is simply as close as we can reasonably get considering our natural exposure to arsenic in the environment and other limitations. At that level, almost all experts agree our drinking water is quite safe." (4)

So if "it remains very unlikely that you have done any harm to yourself or to your children through the drinking of apple juice" and "at that level [10 ug/L], almost all experts agree our drinking water is quite safe," why does he also say that the 4 ug/L of inorganic arsenic in apple juice raises "significant health concerns for us and for our children."

For the life of me I cannot figure this out.  If a child drank two liters of apple juice a day instead of water they would consume less than the MCL of 10 ug/L (ppb) for arsenic that he says "almost all experts agree...is quite safe."

Where is the connection being missed here?  It is - and always will be - about the dose:

"All substances are poisons; there is none which is not a poison. The right dose differentiates a poison…." Paracelsus (1493-1541)

Once more: "The Dose Makes the Poison:"

A substance can produce the harmful effect associated with its toxic properties only if it reaches a susceptible biological system within your body in a sufficient concentration (a high enough dose). The toxic effect of a substance increases as the exposure (or dose) to the susceptible biological system increases. For all chemicals there is a dose response curve, or a range of doses that result in a graded effect between the extremes of no effect and 100% response (toxic effect). All chemical substances will exhibit a toxic effect given a large enough dose. If the dose is low enough even a highly toxic substance will cease to cause a harmful effect. The toxic potency of a chemical is thus ultimately defined by the dose (the amount) of the chemical that will produce a specific response in a specific biological system. (5)

That's from Yale by the way.  But I'll bet you dollars to donuts I could find researchers there who would conclude that arsenic in the apple juice raises "significant health concerns for us and for our children."  Heck, I wrote a bunch of posts on how three public health professionals made the claim that using laundered shop towels posed a risk to employees,  Barbara D. Beck PhD went to Harvard which is in the same league as Yale and she produced two papers that exaggerated the risk of heavy metal exposure.

Where is the connection being missed by these well educated professionals?

Next Post: Apples, Arsenic, and Risk - Part 18: The China Syndrome


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Apples, Arsenic, and Risk - Part 16: The Great and Powerful Oz

Dorothy: Oh, apple juice! Oh - look! Oh!

Scarecrow: Come along, Dorothy - you don't want any of that apple juice. Hmm!

Apple Tree: Are you hinting my apple juice aren't what they ought to be?

Scarecrow: Oh, no! It's just that she doesn't like arsenic in her apple juice!

Apple Tree: Oh, you!  Have you been listening to Dr. Oz and Chuck Norris?

Scarecrow: Yeah.  But I also read about it in Consumer Reports...

Apple Tree: Sigh...Them too?  What did they have to say about my apple juice?

Scarecrow: Stuff like "mounting scientific evidence suggests that chronic exposure to arsenic and lead even at levels below water standards can result in serious health problems."

Apple Tree:  Really, and how much arsenic did they find in my apple juice?

Scarecrow: 3 ug/L...4 if you want to high-side it.

Apple Tree:  And Consumer Reports told you that at that level it could result in serious health problems.

Scarecrow:  Yeah.  And Dr. Oz said the same thing on his web site...that "the findings raise significant health concerns for us and for our children, and have generated incredulousness that this could happen in our country."

Dr. Oz: I am the great and powerful Oz!

Apple Tree: Yeah, so I've been told.

Scarecrow: Chuck Norris said "Poisonous apples are definitely not just being offered in fictional Snow White adventures."
 
Apple Tree:  So my apple juice is poisonous?

Dorothy:  Oh my goodness!  And I've been drinking it.  And Toto too!

Scarecrow:  Consumer Reports says that "arsenic has been notoriously used as a poison since ancient times. A fatal poisoning would require a single dose of inorganic arsenic about the weight of a postage stamp."  A postage stamp!  Do you know how small a postage stamp is!?!

Dorothy: Oh my!

Apple Tree: And how much did they find in my apple juice?

Scarecrow: 4 ug/L.

Apple Tree. How much do you weigh scarecrow?

Scarecrow:  About 70 kilograms

Apple Tree:  Do you know how much Arsenic in a liter of water it would take to kill you or Dorothy?

Doroethy: Oh my, leave me out of this...

Apple Tree:  Well I looked up on the Google and found the weight of a postage stamp.  0.0533 grams.  Do you know how much that is in micrograms?

Scarecrow:  Nope (points to head).  Haven't got a brain, remember?

Apple Tree:  Okay, work with me here.  There are 1000 milligrams in a gram and 1000 micrograms in a milligram.

Dorothy:  This is why Barbie hated math too!

Apple Tree:  Yeah, but this is important.  Everyone is sayin' my apple juice aren't what they ought to be because of arsenic.  They are trying to compare what 0.0533 grams of arsenic will do to you with the 4 micrograms found in my juice.  0.0533 grams is 53,300 micrograms.  The amount needed to kill you is 13,325 times higher than what one liter of my apple juice contains.

Dorothy: Lions, and Tigers, and inorganic arsenic, oh my!

Scarecrow:  Well on the Dr. Oz web page, it does have a Clinical Assistant Professor of Medicine, some guy by the name of Russell H. Greenfield, MD, that tells us:

Arsenic is naturally abundant in our environment in such places as rock formations, minerals and soil, and is also a byproduct of human agricultural and industrial pursuits. Keep this in mind, because it’s important to understand we are all exposed to small, background amounts of arsenic on a regular basis from the food we eat, the water we drink, and the air we breathe. Concerns only arise when considering the type of arsenic (organic or inorganic) we are exposed to, and especially the degree of exposure.

Apple Tree:  Precisely!  Now you're catching on.  Look at the NHAMES study Consumer Reports reviewed.  The average total urinary arsenic is about 8 ug/L.  Now some of that is organic and some inorganic, but that fact is, Americans are exposed to arsenic without drinking apple juice.  It's the dose that's important.  My apple juice has about 4 ug/L of arsenic.  A juice box holds about 8 ounces - or about 0.25 Liters...so that's about 1 ug of arsenic consumed.

Scarecrow: So what your really telling us is that if arsenic exposure is so bad, why don’t you see more people sick or dying from it?’

Apple Tree:  No.  What I'm saying is to consider the dose...the amount of arsenic being consumed from my apple juice in comparison to the total.  The reason you don't see more people getting sick or dying is that the dose we take in is small.

Scarecrow:  Yeah, I thought that would be your argument.  So did Consumer Reports.  They say "many diseases likely to be increased by exposure even at relatively low levels are so common already that its effects are overlooked simply because no one has looked carefully for the connection.”

Apple Tree: So if no one has looked for a connection, does that mean a connection is there?

Scarecrow: Yer' givin' me a headache Apple Tree!  Consumer Reports says that when they did look, "the connections they've found underscore the need to protect public health by reducing Americans’ exposure to this potent toxin."

Apple Tree:  Once again with the potent toxin....

Scarecrow:  Well it is...a postage stamp amount can kill you.

Apple Tree:  We're not dealing with anything near that amount in my apple juice.  Why bring up a potential harm that's not present?  Let's stick to the arsenic in my apple juice, not what's found elsewhere.

Scarecrow: Well...still, they found connections....

Apple Tree:  You mean the type 2 diabetes study and the study showing poorer scores in global cognition, processing speed and immediate memory?

Scarecrow:  Yeah...and Sharyn Duffy's hyperkeratosis...

Apple Tree:  Okay, and even if there was a connection, was that connection based on 4 ug/L in one juice box...or even two juice boxes a day?

Scarecrow: Ahhh...well, even without a brain, consuming more arsenic can't be good.  Isn't it additive?

Apple Tree:  Yes it is.  But were talking 1.4 ug/L more arsenic in apple juice drinkers.  Does 1.4 ug/L create any additional risk for these apple juice drinkers?  Not based on any of the studies Consumer Reports or Dr. Oz presented.

Dorothy: But what if I don't want to consume any more arsenic than I have to?  What if I want to limit Toto's exposure just in case?  If it is a carcinogen there is some risk right?

Apple Tree:  Yes.  And it is perfectly fine for you to choose not to drink my apple juice.  There is no such thing as zero risk, so if reducing the amount of arsenic you take in is something you think prudent, then by all means stop drinking my apple juice.

Dorothy:  And you won't be mad at me?  You won't throw apples at me?

Apple Tree:  Nope.  All I ask is that you don't tell folks that my apple juice aren't what they ought to be.

Dr. Oz: I am the great and powerful Oz.  Pay not attention to that apple tree!

Chuck Norris:  He's part of a government cover-up, chop him down and buy local!

Apple Tree:  I am local you ignorant munchkin!

Dorothy: Oh my!

Apple Tree: Un-tether that balloon and get those two fear-mongers out of here.

Dorothy:  Well I better be going, but which way is the correct way forward?

Apple Tree:  Follow the path the data leads you down, not where the hype sends you.

Dorothy:  But it's all so confusing and scary!  How will I know when there really is a connection?

Apple Tree:  Be objective.  And when you read something that says there is a correlation, click your heals three times and repeat:

Correlation does not imply causation...

Correlation does not imply causation...

Correlation does not imply causation...

Next Post: Apples, Arsenic, and Risk - Part 17: Generated Incredulousness


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Apples, Arsenic, and Risk - Part 15: 19% more...67 years...carry the 2...

Consumer Reports states in their January 2012 report on arsenic in apple juice:

The resulting analysis of almost 3,000 study participants found that those reporting apple-juice consumption had on average 19 percent greater levels of total urinary arsenic than those subjects who did not.

If the average total urinary arsenic [NHANES] for 12-18 year old's is 8.55 ug/L, Apple juice drinkers would be - on average - 19% higher than that, or 10.17 ug/L.

The "long-term low-level arsenic exposure" was calculated as follows:

We estimated long-term low-level exposure by multiplying current estimated arsenic levels by the number of years residing in current home.

So an 18 year old would have a long-term low-level arsenic exposure of 18 x 8.55 = 153.9 ug/L-year.

And the 18 year old apple juice drinker would have a long-term low-level arsenic exposure of 18 x 10.17 = 183.1 ug/L-year.

So if the unstandardized regression coefficient - B - results are as reported, these are the scores we would predict between the two groups, average & apple juice drinkers, over an 18 year exposure period.

I ran their data in an Excel spread sheet so I could see what the difference would be between the two scores.  That's found in the last column at the bottom.  Notice how not one of those tests has a decrease or increase in the score over one (1).

The question I have is this: If the linear regression calculates an unstandardized regression coefficient called "B," and that we interpret an unstandardized regression coefficient as follows:

For every metric unit change in the independent variable, the dependent variable changes by X units.

The change in score these researchers report is so small as to be of little value.  Yet what was reported in this paper was used by Consumer Reports to make the claim that low-levels of arsenic below the drinking water MCL of 10 ug/L presents "a chronic problem" "related to poor scores in language, memory, and other brain functions."

Consumer Reports is using the conclusion of this paper to support their claim that:

Mounting scientific evidence suggests that chronic exposure to arsenic and lead even at levels below water standards can result in serious health problems.

Is this the" mounting scientific evidence" they are using to support their claim that low-level exposure is related to poor scores in language, memory, and other brain functions?

Did the researchers from Texas Tech and the University of North Texas find that "long-term low-level exposure to arsenic was significantly associated with poorer scores?"

Yes.  And that's the problem that needs to be addressed.

Numbers mean something.  Those "Bs" reported are valid in supporting their conclusion:

Our findings suggest an association between low-level arsenic exposure and neuropsychological functioning, as originally hypothesized. Of particular interest is the association between long-term low-level arsenic exposure and neuropsychological functioning across a broader range of domains than current exposure. Our findings offer the first direct evidence that low level arsenic exposure, extrapolated from current arsenic levels and self report of duration in residence is associated with poorer neuropsychological functioning among community-dwelling adults and elders in the U.S.

They found an association and the statistics - the p-value - supports it.  But what did they really find?

Or, more importantly, did they see results that would support lowering the level of arsenic deemed safe?  Are their results strong enough to stop us from drinking apple juice?  Should we, on the basses of a -0.001 change in a score require apple juice providers to reduce the concentration of arsenic from and average of 4 ug/L to 3 ug/L?

Why did four researchers produce this paper, and why did it it get published in a peer review journal?  Because there is nothing wrong with it in terms of it meeting the standards for publishing.

It's valid, it's honest, it's conclusion is correct.  Unfortunately it does not support the claim of "mounting scientific evidence suggests that chronic exposure to arsenic and lead even at levels below water standards can result in serious health problems."

It shows something that means nothing.  And that right there leads Consumer Reports, Dr. Oz, and good ol' Chuck Norris down the path of requiring a change where one is not needed.

As our investigation found, when scientists and doctors do look, the connections they’ve found underscore the need to protect public health by reducing Americans’ exposure to this potent toxin.

Why is this a big deal?  Let me quote the Texas Commission on Environmental Quality (TCEQ) once again:

[I]f erring on the side of conservatism significantly overestimates risk or hazard and is not  fully  justified, then harm to public health may result from diverting public, industry, and government attention and resources away from chemicals which may represent more of a public health risk at environmental levels. (TCEQ)

Next Post: Apples, Arsenic, and Risk - Part 16: The Great and Powerful Oz

Apples, Arsenic, and Risk - Part 14: A poorer score of -0.001

Once more....

Consumer Reports claims in their January 2012 article on arsenic in apple juice:

Mounting scientific evidence suggests that chronic exposure to arsenic...even at levels below water standards can result in serious health problems.

A 2011 study examined the long-term effects of low-level exposure on more than 300 rural Texans whose groundwater was estimated to have arsenic at median levels below the federal drinking-water standard.

It found that exposure was related to poor scores in language, memory, and other brain functions.

What I want you to focus on is "even at levels below water standards" and "exposure was related to poor scores in language, memory, and other brain functions."

In my last post I looked at these two claims by the studies authors:

1. Current estimated groundwater arsenic exposure level was significantly associated with poorer scores in language, visuospatial skills, and executive functioning. 
2. Current arsenic exposure significantly classified cognitive dysfunction. 

In this post I want to look at their conclusion for what the term "long-term low-level arsenic exposure:"

We estimated long-term low-level exposure by multiplying current estimated arsenic levels by the number of years residing in current home.

I'm not going to make an argument as to whether or not that that's a valid methodology.  I don't need to.  The B(SE) they report in Table 3 tell me there is nothing to be concerned about:

Source

Once again, I'm no linear regression expert or statistical astute person.  What I know about something is what I have been taught and what is consistently discussed.  I may be wrong on how to interpret those B(SE) scores, but I don't think I am. (Comments are on - feel free to skool' me)

Here is what the Google says about an "unstandardized regression coefficient" - "B":

To interpret an unstandardized regression coefficient: for every metric unit change in the independent variable, the dependent variable changes by X units. For instance, if income is the dependent variable, and years of education is one of the independent variables, and the unstandardized regression coefficient for education is 3,000, then this would mean that for very additional year of education a respondent has, their income increases by $3,000.00 (controlling for the other independent variables in the equation). (1)

and...

As you may remember, in a linear regression model the estimated raw or unstandardized regression coefficient for a predictor variable (referred to as B) is interpreted as the change in the predicted value of the dependent variable for a one unit increase in the predictor variable. Thus a B coefficient of 1.0 would indicate that for every unit increase in the predictor, the predicted value of the dependent variable also increases by one unit. In the common case where there are two or more correlated predictors in the model, the B coefficient is known as a partial regression coefficient, and it represents the predicted change in the dependent variable when that predictor is increased by one unit while holding all other predictors constant. (2)

Let's take the example in the first blurb.

"if income is the dependent variable" will now become "if RBANS Visuopatial score is the dependent variable."

"years of education is one of the independent variables" will now become "long-term low-level arsenic exposure is one of the independent variables."

"and the unstandardized regression coefficient for education is 3,000" will now become "and the unstandardized regression coefficient for  RBANS Visuopatial  is -0.001"

"then this would mean....."

"that for very additional ug/L-year of arsenic a rural Texan is exposed to, their  RBANS Visuopatial score decreases by 0.001 (controlling for the other independent variables in the equation)

Please tell me I am wrong in how this is to be interpreted.  Please don't tell me that these four researchers from Texas Tech and the University of North Texas reported that:

However, we can assert that those individuals who have resided for long periods of time in regions that have historically low levels of arsenic in groundwater supplies are at increased risk for cognitive dysfunction.

...based on unstandardized regression coefficient - B - results as follows:

• MMSE: −0.003
• CLOX 2: −0.001
• FAS: −0.012
• RBANS Language: −0.005
• TMTA:  0.034
• EXIT: 0.006
• RBANS Immediate Memory: −0.010

How does a change in score of -0.003 for each ug/L-year arsenic exposure constitute an "increased risk for cognitive dysfunction?"

Let me do some math...."long-term low-level arsenic exposure:"

We estimated long-term low-level exposure by multiplying current estimated arsenic levels by the number of years residing in current home.

So the ug/L-year = Estimated Arsenic Level x Number of Years in Home...Looking at Table 2....

Source

So....240.15 / 6.33 = 37 years...nah, that can't be right.  972.83 / 15.26 = 63 years.  I'm not sure how they calculated that number of 240.15.  If the highest range was 972.83 ug/L-years and the highest arsenic range was 15.26 ug/L that would mean 63 years of exposure in the same house.  That's possible, I guess, especially for a rural community.

The unstandardized regression coefficient states the for every metric unit change in the independent variable, the dependent variable changes by X units.  So the "X" units we are talking about is the score.  What I don't know is the unit change we could use to calculate that predicted score.

The long-term arsenic range is 2.87 - 972.83 ug/L-years.  I'll assume that the unit change is one ug/L-year.  This would equate to a difference of 972.83 - 2.87 = 969.96 units of change.

If we take that number - 969.96 and multiply it by the B values reported as "significantly associated with poorer scores" we would expect the following score changes for a person exposed to 15.26 ug/L of arsenic for 67 years:

• MMSE: −0.003 x 969.96 = -2.9
• CLOX 2: −0.001 x 969.96 = -0.96
• FAS: −0.012  x 969.96 = -11.6
• RBANS Language: −0.005  x 969.96 = -4.8
• TMTA:  0.034  x 969.96 = 32.9
• EXIT: 0.006  x 969.96 = 5.8
• RBANS Immediate Memory: −0.010  x 969.96 =  -9.6

I'm not sure that a unit of change is calculated like that, but based on a worst case scenario, and from what the Google tells me about how an "unstandardized regression coefficient" works, that's the changes in scores I would predict for a 67 year long exposure to 15.26 ug/L of arsenic.

What would we predict for a person who consumes apple juice for 67 years?


Next Post: Apples, Arsenic, and Risk - Part 15: 19% more...67 years...carry the 2...


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Apples, Arsenic, and Risk - Part 13: How much is "19 percent higher levels?"

My last post had me looking at a study Consumer Reports states in their January 2012 report on arsenic in apple juice that:

A study published in 2011 in the International Journal of Environmental Research and Public Health examined the long-term effects of low-level exposure on more than 300 rural Texans whose groundwater was estimated to have arsenic at median levels below the federal drinking-water standard. It found that exposure was related to poor scores in language, memory, and other brain functions.

This study used linear regression to:

Examine the potential association between current and long-term arsenic exposure and detailed neuropsychological functioning in a sample of rural-dwelling adults and elders.

What we know so far is this:

• Linear regression models were created using raw neuropsychological test scores as outcome variables and either current or long-term arsenic exposure estimates as predictor variables.
• Linear regression is when you want to predict values of one variable, given values of another variable.

So what we can see from Table 3:

Source

Is that when the current arsenic level increases by one unit, the  "RBANS Language scores" decrease by 0.458 (controlling for the other independent variables in the equation).  That's the prediction of their linear regression model for RBANS Language Scores [−0.458 (p = 0.008)].

For the 13 tests administered, the study found that current GIS-based groundwater arsenic exposure was significantly related to poorer scores for three of the tests:

• RBANS Language scores B(SE) = −0.458 (0.171), p = 0.008
• Visuospatial skills CLOX2, B(SE) = −0.118 (0.060), p = 0.048
• Executive functioning CLOX1 B(SE) = −0.225 (0.080), p = 0.005

So for the sake of argument (and to give me something to write about) let's say that this model is predictive as the authors claim.  How much "poorer" would the scores be for children who drink apple juice?

According to Consumer Reports:

The resulting [NHANES] analysis of almost 3,000 study participants found that those reporting apple-juice consumption had on average 19 percent greater levels of total urinary arsenic than those subjects who did not.

Interesting....remember this table from NHANES:

Source

The mean and (95% CL) for kids 6-11 years old is 7.08 (5.68-8.84).

With that, we can calculate how much "19% more total urinary arsenic" would be for 6-11 year old kids who drink apple juice.

Do some math...carry the 2....7.08 x 1.19 = 8.43 ug/L

So apple juice drinking 6-11 year old kids have 1.35 ug/L more arsenic.  If the linear regression model in this study is correct, we would predict their scores to decrease as follows.  The "B" represents the slope of the regression line--the amount of change in Y due to a change of 1 unit of X:

• RBANS Language scores: -0.618
• Visuospatial skills CLOX2: -0.159
• Executive functioning CLOX1: -0.304

Is that decrease in score a concern?  Look at the standard deviations for the test results in Table 2.  (CLOX means are not listed by the authors, I am assuming their range is similar to the other tests)

Source

For RBANS Language the standard deviation is 5.46 points.  Our little apple juice drinkers would see a decrease in their scores of 0.618.

"But"...you say..."the results might understate the correlation between juice consumption and urinary arsenic levels because NHANES urinary data exclude children younger than 6, who tend to be big juice drinkers."

Let's up the arsenic to that found in males; 9.50 ug/L.  19% more...carry the 2...9.50 x 1.19 = 11.3 ug/L

So...2.25 ug/L more arsenic...or 2.25 units...2.25 x -0.458 = 1.03 points lower for RBANS Language.  That's assuming their model holds true.   Look at the range of results they got; 8 - 42.  Would a decrease of one point indicate a concern?  Is this what Consumer Reports means when they state:

"Mounting scientific evidence suggests that chronic exposure to arsenic...even at levels below water standards can result in serious health problems."

But all that's for the current arsenic level.  Let's look at what they found when they ran the linear regression with long-term arsenic - ug/L-years.


Next Post: Apples, Arsenic, and Risk - Part 14: A poorer score of -0.001

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Apples, Arsenic, and Risk - Part 12: Correlation does not imply causation

In my last post I asked the question:

What about Consumer Reports telling its readers about a 2011study in the International Journal of Environmental Research and Public Health that examined the long-term effects of low-level exposure on more than 300 rural Texans whose groundwater?

Consumer Reports claims in their January 2012 article on arsenic in apple juice that these Texans were estimated to have exposure to arsenic at median levels below the MCL and when tested showed poor scores in language, memory, and other brain functions.

That brings me to asking this question: will "low-levels" of arsenic, as was found in the apple juice samples tested by Consumer Reports lead adversely affect those that consume apple juice?  Here is what they state at the beginning of their report:

Mounting scientific evidence suggests that chronic exposure to arsenic...even at levels below water standards can result in serious health problems.

I've looked at cancer, hyperkeratosis, and type 2 diabetes, that leaves this one last study on chronic exposure to look at.  Will this support their claim that levels below the MCL can result is serious health problems?

Here is what Consumer Reports tells their readers about this 2011 study:

It found that exposure was related to poor scores in language, memory, and other brain functions.

Here is what that paper concludes:

The results of the study showed that GIS-based groundwater arsenic exposure (current and long-term) was significantly related to poorer scores in language, visuospatial skills, and executive functioning. Additionally, long-term low-level exposure to arsenic was significantly correlated to poorer scores in global cognition, processing speed and immediate memory.

"Significantly related" and "significantly correlated."

Two things to keep in mind here:

1. The term "significantly" is in reference to statistics.  That is, it is unlikely to have occurred by chance.  Not significant as in "sufficiently great or important to be worthy of attention."
2. The term "correlated" means a statistical measurement of the relationship between two variables.

So "significantly correlated" means a relationship between two variables that is unlikely to have occurred by chance.

Rule number one about correlations:  They do not imply causation!!!

Source

...and so it goes with low-levels of arsenic in our our apple juice and water.

Let's look at the table of results:

Source

I am by no means a statistician, nor am I really that versed to expertly explain "unstandardized regression coefficient" as it is derived from a "linear regression" model.  For more info on this see 1, 2, 3, or 4.

What I do understand about this table is this:

Linear regression models were created using raw neuropsychological test scores as outcome variables and either current or long-term arsenic exposure estimates as predictor variables.

So....

Simple linear regression is when you want to predict values of one variable, given values of another variable.

The purpose of regression analysis is to come up with an equation of a line that fits through that cluster of points with the minimal amount of deviations from the line. The deviation of the points from the line is called "error."

Once you have this regression equation, if you knew a person's Long-term or current arsenic level of exposure, you could then predict their score on one of the  neuropsychological tests administered.

The data in Table 3 is reported for:

B = unstandardized regression coefficient.

So...

B coefficients are interpreted as the amount of change in the dependent variable (Y) that is associated with a change in one unit of the independent variable (X).

All B coefficients are unstandardized, which means that the magnitude of their values is relative to the means and standard deviations of the independent and dependent variables in the equation.

It represents the slope of the regression line--the amount of change in Y due to a change of 1 unit of X.

The unstandardized coefficients are used for actually making a prediction, using the independent variables as they were measured.  For example, if a variable is in dollars, the unstandardized coefficient is in dollars, if a variable is in inches, it is in inches.

What Table 3 tells us is this:

If "RBANS Language scores" is the dependent variable, and "current arsenic level" is one of the independent variables, and the unstandardized regression coefficient (B) for  "RBANS Language scores"  is −0.458 (p = 0.008), then this would mean that for every additional ug/L of arsenic exposed to, there would be a decrease of 0.458 in the RBANS Language scores  (controlling for the other independent variables in the equation).

Remember, correlation does not imply causation.  In other words, it may not be the arsenic that drops the score but something else going on.  For example, there was an increase in polio cases correlated to the amount of ice cream sold.  Ice cream was not the cause of polio, polio cases increased in the summer as did sales of ice cream.

But let's say that this model is predictive, as the authors claim:

Groundwater arsenic exposure (current and long-term) was significantly related to poorer scores in language, visuospatial skills, and executive functioning.

What "serious health problems" - or in this case - how much "poorer" would the scores be for children who drink apple juice?

Next post: Apples, Arsenic, and Risk - Part 13: How much is "19 percent higher levels?"


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Apples, Arsenic, and Risk - Part 11: Type 2 diabetes - 80th vs the 20th percentiles

How to make a weak association sound strong:

1. Present the data in a format to disguise the weakness (2% instead of 1.02)
2. Compare percentiles to increase the ORs reported.

Now please don't get me wrong here, there is a perfectly good reason to compare percentiles.  Was this one of them?  I don't think it was done for any other reason than to bolster the paper's claim that there is a positive association between arsenic and type 2 diabetes prevalence.

But let's assume that there is no sneaky reason for presenting this data in her report.

If that's the case, then let me ask this question: Does the OR for the 20%/80% percentile support Consumer Report's claim that there is a link between "low-level arsenic exposure with the prevalence of type 2 diabetes in the United States?" And, if so, will the concentration of arsenic they found in the apple juice they tested be high enough to increase the risk for developing type 2 diabetes?  That is, after all, what is meant by "there is a positive association between arsenic and type 2 diabetes prevalence."

What do we know so far from Dr. Ana Navas-Acien's study on arsenic and type 2 diabetes?  Well we know that for the 93 participants in the study who had type 2 diabetes, their average total arsenic was 6.2 ug/L as you can see in Table 2:

Source

We also know that the third model "was further adjusted for urine arsenobetaine and blood mercury levels" to provide "estimates for the association of inorganic arsenic not derived from seafood and for arsenobetaine."

And we know that the ratio of arsenic concentrations comparing participants with type 2 diabetes for Model 3 was 1.26 (1.02-1.56) as can be seen in Table 2 above.

So...an average of 6.2 ug/L total arsenic generated an OR of 1.26 (1.02-1.56) when it was further adjusted for urine arsenobetaine and blood mercury levels.

What's the average urinary total arsenic they found in the 2003-2004 NHAMES study?

Source

We're going to use this Table again in an upcoming post, it's important here because we need to understand what is meant by the term "low-level arsenic exposure."

There is a weak association when you look at Model 3 because the range is just barely above "1" - (1.02-1.56).  Because that range does not include the number "1", Dr. Ana Navas-Acien can report a "positive" association:

This finding supports the hypothesis that low levels of exposure to inorganic arsenic in drinking water, a widespread exposure worldwide, may play a role in diabetes prevalence.

and...

These results support our hypothesis that exposure to inorganic arsenic, which in this population was most likely derived from drinking water, is associated with an increased risk of diabetes.

and again...

We found a positive association between total urine arsenic, likely reflecting inorganic arsenic exposure from drinking water and food, with the prevalence of type 2 diabetes in a population with low to moderate arsenic exposure.

Which brings me once again to my question: how much confidence in that number do you have?

Had the paper stopped at:

After adjustment for diabetes risk factors and markers of seafood intake, participants with type 2 diabetes had a 26% higher level of total arsenic...

...we would only have an argument on including the word "weak" to describe the association.  Attach a verb, don't attach a verb, toe-mate-o, toe-maut-o.

Now look at the rest of the "results" paragraph in the abstract at the beginning onf the paper:

After similar adjustment, the odds ratios for type 2 diabetes comparing participants at the 80th vs the 20th percentiles were 3.58 for the level of total arsenic (95% CI, 1.18-10.83).

1.26 now jumps to 3.58.  And the 95% CI range is now (1.18-10.83).

Stout! ...or is it robust?

There's one slight problem here.  Are we still talking about "low-level arsenic exposure?"

Look at Table 3....

Source

Notice what the urinary total arsenic concentration is for the 80th percentile?  16.5 ug/L compared to the 20th percentile of 3.0 ug/L.  What's the geometric mean - average - they report?  6.2 ug/L compared to 7.3 ug/L.  Hmmm...interesting.

So let's reword that results statement to reflect what is really going on here.

When Dr. Ana Navas-Acien writes:

After similar adjustment, the odds ratios for type 2 diabetes comparing participants at the 80th vs the 20th percentiles were 3.58 for the level of total arsenic (95% CI, 1.18-10.83

What she really is stating is this:

After similar adjustment, the odds ratios for type 2 diabetes comparing participants with a  urinary total arsenic of 16.5 ug/L (almost three times the average) with those without type 2 diabetes and a urinary total arsenic of 3.0 ug/L (less than half the average), were 3.58 (1.18-10.83)

That statement above is factual and accurately describes the results from Table 3.

To get that high of an odds ratio the arsenic has to be almost three times the average level normally found in the population.  And, to top it off, it will only be that high if it is compared to a population that has 2 time less arsenic than the population as a whole.

16.5 ug/L is not a low level of arsenic.  It is above the MCL of 10 ug/L and way above the 4 ug/L Consumer Reports found in the samples of apple juice they tested.

Well Mr. Smarty-Pants, doesn't it also show that increasing the level of arsenic increases the risk of type 2 diabetes!  Explain that you wet blanket!

Yeah, it does show that, but it is based on a sample size which, surprise! surprise! is not referenced (at least I can't find it).

What is the "n" making up the 80th percentile of those with type 2 diabetes and what is the "n" for the 20th percentile for those without?  Remember, we started with 93/695 and then adjusted it once - Model 1, then again, Model 2, then even more, Model 3.  What's the "n" of two populations used in the OR for Model 3?  And then from that population they separated it further into percentiles, what's the "n" of the 80th and the "n" of the 20th?

In statistics, the error - bias - is reduced with more "n"s.

There is, however, another interesting bit of information you can get from Table 3.  Look at the next three columns called "Tertile"

What's a "tertile?":

Any of the two points that divide an ordered distribution into three parts, each containing a third of the population.

You know something you can get from those three tertile columns?  The total "n" of each population that made up that tertile.

So if the 80th percentile is 16.5 ug/L and the highest third of all the data is >10.8 ug/L, how many of the 34 "n" to in the third tertile of Model 3 are in the 80th percentile?

What's also interesting is that when  Dr. Ana Navas-Acien compared the lowest population, the middle, and the highest, there was no statistical significance in any of the pairings.  None.  They all contain the number "1" in the ranges.

I think I'm done looking at this paper.  It has too many issues to accept its claim that:

This finding supports the hypothesis that low levels of exposure to inorganic arsenic in drinking water, a widespread exposure worldwide, may play a role in diabetes prevalence.

So, low-levels of arsenic - below the MCL and at the levels found in apple juice - do not support a link to cancer, hyperkeratosis, and type 2 diabetes.  Is that it?  Can I move on to something else, you know, like hazardous waste being wacky?

What about Consumer Reports telling its readers about a 2011study in the International Journal of Environmental Research and Public Health that examined the long-term effects of low-level exposure on more than 300 rural Texans whose groundwater?

Consumer Reports claims that these Texans were estimated to have exposure to arsenic at median levels below the MCL and when tested showed poor scores in language, memory, and other brain functions.  What about low levels of arsenic and diminished intelligence?  Isn't that a problem?

Rule number one: Always read the report the findings/recommendations were based on.

Onward...to infinity and..../sigh

Next Post: Apples, Arsenic, and Risk - Part 12: Correlation does not imply causation.


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Apples, Arsenic, and Risk - Part 10: Type 2 diabetes - 1.26 based on what?

In my last post I ended with the question of how much confidence should we have in this Odd Ratio: 1.26 (1.02-1.56)?

The reason for our confidence in it, how solid it is, how much it actually reflects the population it measures, is because it is used to generate the conclusion:

This finding supports the hypothesis that low levels of exposure to inorganic arsenic in drinking water, a widespread exposure worldwide, may play a role in diabetes prevalence.

And with that conclusion, Consumer Reports was able to tell its readers that there is a link between:

Low-level arsenic exposure with the prevalence of type 2 diabetes in the United States.

Although it may seem like I am beating a dead horse with all of this, I mean c'mon 10 posts?!?, what I am trying to do is take a complicated subject and break it down so one can separate fact from spin.

Step one is being skeptical, even if the work is performed by a respectable organization like Consumer Reports with help from a Johns Hopkins University’s Bloomberg School of Public Health physician - epidemiologist.

Step two is reading the work that is used to support the claim.  Consumer Reports and their scientists claim that low levels of arsenic is harmful.  We know from their 84 samples analyzed for inorganic arsenic the mean level of inorganic arsenic is 4 ug/L or 4 ppb.  We know that the EPA has established an MCL for arsenic in drinking water of 10 ppb based on a 70 kg person consuming 2 liters per day for a lifetime as a "safe" level.  Is 4 ppb arsenic in the apple juice a concern?  Is it a concern for contributing to type 2 diabetes?

Step three is looking at the data.  Looking at it closely to see how it was derived and concurring with the author or disregarding the findings as unsupported.

Here's the thing I want the reader to know.  If her work supported her conclusion I would still write about it and show why.  It doesn't, which is why it takes this direction.  If it did, I would go in that direction. I've got no dog in this hunt as well.

So let's look at how those ORs we derived.  Starting with Table 2:

Source

Here is how they got their "n":

• They randomly selected a one-third random sample of NHANES 2003-2004 study participants aged 6 years and older (n=2673)
• They then selected 1027 participants from those 2673 who had fasted 8 to 24 hours before venipuncture.
• They then excluded 38 pregnant women, 34 participants missing total urine arsenic or urine arsenic species, 24 participants without prior diagnosis of diabetes missing serum glucose, 4 participants missing glycated hemoglobin, 
• They then restricted their analyses to participants who did not report seafood intake in the past 24 hours.

That last bullet was done for this reason:

Our primary assessment of exposure was total urine arsenic concentration adjusted for objective biomarkers of seafood consumption.

So far, so good.  This gave them a total population of 788 (n = 788).

Of that 788, 95 had type 2 diabetes and 695 did not.  All of the OR and percentages they now report will be based on that population.  They are comparing one group to another - those with diabetes to those without.

The hypothesis here is that you will see a higher urinary arsenic level for those with diabetes compared to those without.

Doh!  That's not what they saw when the compared the mean total arsenic in the diabetes group with that of the non-diabetes.  Seems the non-diabetes group had more 7.4 ug/L compared to 6.2.

Now there could be a logical reason for this based on the makeup of the two groups being compared.  We want to compare a similar group with a like similar group.  Instead we are dealing with a random group we pulled from a larger group.  Enter the "Model."

Model 1:

First, we adjusted for sex, age, race and ethnicity (known determinants of diabetes that may be related to arsenic exposure), and urine creatinine.

Okay, even with that adjustment there is still less total arsenic in the diabetes group compared to the non-diabetes group.  0.94 OR, but the range contains a "1" so we can conclude nothing there, although it is consistent with what we see with the raw data.

Model 2:

Second, each model was further adjusted for education, body mass index, serum cotinine, and use of antihypertensive medication.  This model represents the association of total arsenic exposure with diabetes independent of the source but adjusted for traditional diabetes risk factors.

Okay, now there is a shift, based on this model, 1.01, but again, the range contains a "1" so this model statistically shows no association.

Model 3:

Third, each model was further adjusted for urine arsenobetaine and blood mercury levels. This model provides estimates for the association of inorganic arsenic not derived from seafood and for arsenobetaine.

So after adjusting for 1 & 2, they further adjust the population by excluding those who were found to have arsenobetaine and blood mercury levels.  The assumption here is that these folks ate fish and their total arsenic is tainted by organic arsenic from the fish.

Aha!  Now we get a positive association, the 1.26 with a range of 1.02-1.56.  Woot!  Now they can claim a positive association!  There ain't a "1" in that range is there!

Now before we continue, you might be wondering about other risk factors for type 2 diabetes:

Further adjustment for smoking status and alcohol intake, as well as exclusion of participants showing levels below the limit of detection, did not modify the observed associations.

With all that adjusting going on our populations being compared get smaller and smaller allowing the influence of sample error to have a greater role in the accuracy and precision of the number reported.  This is why it is hard for me to accept a positive association where the range is 1.02-1.56.

You'll notice how at the beginning of their paper - the only part 99% of all journal paper readers read - it does not report these ORs, instead it reports a percentage:

The prevalence of type 2 diabetes was 7.7%. After adjustment for diabetes risk factors and markers of seafood intake, participants with type 2 diabetes had a 26% higher level of total arsenic (95% confidence interval [CI], 2.0%-56.0%) and a nonsignificant 10% higher level of dimethylarsinate (95% CI, −8.0% to 33.0%) than participants without type 2 diabetes, and levels of arsenobetaine were similar to those of participants without type 2 diabetes.

I wonder why?

Well for starters, 26% higher sounds much more significant than 1.26.  And 2.0% - 56% sounds more pronounced than 1.02-1.56.  Yeah it means the same thing, but the perception is different, that's why we sell stuff at $9.99 and not $10.00.  Kind of sneaky isn't it?  It's not lying, but it's not being forthright either.  It's spin.  Ahh the games you must play when your results are weak.

But wait...we can make support for our hypothesis even stronger!  Let's compare percentiles!  Now we can report an OR that's got a bit of meat on its bones!

After similar adjustment, the odds ratios for type 2 diabetes comparing participants at the 80th vs the 20th percentiles were 3.58 for the level of total arsenic (95% CI, 1.18-10.83), 1.57 for dimethylarsinate (95% CI, 0.89-2.76), and 0.69 for arsenobetaine (95% CI, 0.33-1.48).

Much...much better wouldn't you conclude?  That's brings us back to Figure 2 in my last post, the one with the graphic showing how many "favors association."

Rule number one: Always read the report the findings/recommendations were based on.


Next Post: Apples, Arsenic, and Risk - Part 11: Type 2 diabetes - 80th vs the 20th percentiles


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