Apples, Arsenic, and Risk - Part 8: Arsenic and type 2 diabetes

"Mounting scientific evidence...serious health problems..."

Okay...so where are we after seven posts?

"For water with 10 ppb of arsenic, the excess cancer risk is one in 500."  That's been addressed and found to be based on a cancer slope - potency - that is not seen in the real world.  So water or apple juice with less than 10 ppb of arsenic is not a cancer risk.

"Sharyn Duffy of Geneseo, N.Y. having "double the typical levels" of arsenic causing her to develop hyperkeratosis.  "Double the levels" of arsenic would not bring about that disease.  We can ignore that claim of a health problem at low levels - below the MCL.

What else does Consumer Reports claim is the harm associated with low levels of arsenic?

Ana Navas-Acien, M.D., Ph.D., a physician & epidemiologist at Johns Hopkins University’s Bloomberg School of Public Health, also provided guidance. She was the lead author of a 2008 study in the Journal of the American Medical Association (PDF) that first linked low-level arsenic exposure with the prevalence of type 2 diabetes in the United States.

OK, that's probably what lead to Consumer Reports making this statement about arsenic:

It’s a carcinogen known to cause bladder, lung, and skin cancer in people and to increase risks of cardiovascular disease, immunodeficiencies, and type 2 diabetes.

Since EPA has set the reference dose (RfD or MRL) for arsenic based on this:

"This value [0.0008 mg As/kg/day] has been used to calculate a chronic oral MRL for inorganic arsenic of 0.0003 mg/kg/day."

And that value - 0.0008 mg AS/kg/day - was derived from....:

 "a very large study detected no effects in any person at an average total daily intake (from water plus food)."

Where they found "no effects" at that level for....

"Skin lesions." 

What EPA'a ATSDR take on low levels of arsenic is this: A chronic daily intake of 0.0003 mg/kg/day of arsenic will result in no skin lesions.  What it also tells us is that all other diseases associated with arsenic result from concentrations higher than what causes skin lesions.  So if ATSDR sets the protection based on skin lesions it will be protective for all the other diseases at or below that level.  That 0.0003 mg/kg/day is what gives you the 10 ppb MCL for drinking water.

Not so fast, says Dr. Ana Navas-Acien:

After adjustment for biomarkers of seafood intake, total urine arsenic was associated with increased prevalence of type 2 diabetes. 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 this claim bears a bit of scrutiny.  She is one of the scientists Consumer Reports used in their report and they make reference type 2 diabetes as a possible health concern from low levels of arsenic.

This puts us once again back to the question:

1. Is drinking apple juice unsafe because of arsenic?
2. Is drinking water with the 10 ug/L (ppb) of arsenic unsafe?

What does Dr. Ana Navas-Acien mean when she reports "low levels of exposure to inorganic arsenic in drinking water...may play a role in diabetes prevalence."  What "low levels" is she talking about?  Below the MCL?

Confusing. So lets look at what we know.

We know we have apple juice that Consumer Reports found to contain about 4 ppb of arsenic at the 95%CI.  We know we have drinking water that the EPA states will not result in and deleterious effects during a lifetime at 10 ppb.  And now we have a scientist - epidemiologist no less - from Johns Hopkins University’s Bloomberg School of Public Health, telling us there may be link to type 2 diabetes at low levels.

Help me, Obi-Wan Kenobi. You're my only hope.

Well I ain't no Obi-Wan Kenobi, but I can point you in a direction to help make sense of this, at least that's what I am trying to do.

Let's look at what Dr. Ana Navas-Acien concludes in her study:

"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."

Powerful.  Reading that one would have to conclude that arsenic contributes to type 2 diabetes, and at low levels to boot!  But if you look at her paper closely - and understand what a "positive association" means - you might come away with a much different level of concern about low levels of arsenic and type 2 diabetes.

I've said it before: Always read the journal article, not just the abstract or the conclusion.  This is another example of the truth, whole truth, and nothing but the truth, showing the disingenuous side of scientific research and publication.  I'm not the quickest study, it usually takes me three or or four times to understand what went on and what the data says.

So, first question: Did Dr. Ana Navas-Acien find "a positive association" between inorganic arsenic and type 2 diabetes?  Yes.  Is that "association" the whole truth?  No.  It's all in her "peer reviewed" paper, all you need to do is understand how a positive association works and how to interpret her data.

First, a bit of ground rules for understanding any data presented in a scientific journal article:

When we say" 95% CI" - upper confidence interval - we mean this:

“because of the uncertainty associated with estimating the true average concentration...the 95 percent upper confidence limit (UCL) of the arithmetic mean should be used for this variable.”  That is, we are taking the highest value that statistically would fall within two standard deviations from the mean and not using the average (mean) or median. (1)

When we say "P-value" we mean this:

A P value is the probability of obtaining the observed effect (or larger) under a ‘null hypothesis’, which in the context of Cochrane reviews is either an assumption of ‘no effect of the intervention’ or ‘no differences in the effect of intervention between studies’ (no heterogeneity).

Thus, a P value that is very small indicates that the observed effect is very unlikely to have arisen purely by chance, and therefore provides evidence against the null hypothesis.  

It has been common practice to interpret a P value by examining whether it is smaller than particular threshold values. In particular, P values less than 0.05 are often reported as “statistically significant”, and interpreted as being small enough to justify rejection of the null hypothesis. 

However, the 0.05 threshold is an arbitrary one that became commonly used in medical and psychological research largely because P values were determined by comparing the test statistic against tabulations of specific percentage points of statistical distributions. (2)

That is, when we see a P-value of less than 0.05 we can statistically assume there was an effect or there is an association.  Remember, association does not imply causation!

When we look at an Odds Ratio - OR - we need to adhere to the following when reviewing the range they report with it:

• Conclude that the probability that the outcome is present is higher (in the population) for group 1 if the entire interval is above 1
• Conclude that the probability that the outcome is present is lower (in the population) for group 1 if the entire interval is below 1
• Do not conclude that the probability of the outcome differs for the two groups if the interval contains 1

That last bullet is the important one.  If the range include the number one - "1" - there is no difference between the two groups that is statistically sound - regardless of what Odds Ratio is reported.

Okay, so now that we got that little bit of fun out of the way, lets look at Dr. Ana Navas-Acien's conclusion that there is a positive association between total urine arsenic with the prevalence of type 2 diabetes in a population with low to moderate arsenic exposure.


Apples, Arsenic, and Risk - Part 9: Type 2 diabetes - A very weak link.

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