Image Credit: Wild Rose College
A new study reporting the ranges of values for kidney and liver parameters in a healthy population is being actively misrepresented by anti-fluoride campaigners. The Fluoride Action Network’s (FAN) latest bulletin claims the study shows “that fluoride at commonly experienced doses can damage the kidneys and livers of adolescents.”
The study shows nothing of the sort. How could it – individuals suffering liver or kidney disease were specifically excluded from the study population. The reported parameter values are all for healthy individuals.
Readers can check for themselves – there is a free download. The paper is:
Malin, A. J., Lesseur, C., Busgang, S. A., Curtin, P., Wright, R. O., & Sanders, A. P. (2019). Fluoride exposure and kidney and liver function among adolescents in the United States: NHANES, 2013–2016. Environment International,
It is important to understand what this study really found. Not only is it being misreported by anti-fluoride activists. The University (The Mount Sinai Hospital/Mount Sinai School of Medicine) press release also appears to attribute more to the study’s findings than is warranted. This is a common problem with university public relations departments. (Readers are warned – the press release includes the disclaimer:
“AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system”
Below I list some information on the study
This is not a study about kidney or liver disease
Individuals showing such disease were specifically excluded. The study reports values for kidney and liver parameters in “generally healthy” subjects. The authors make this very clear in the discussion saying:
“this study did not aim to determine whether fluoride exposure is associated with clinical decrements in kidney function among U.S. adolescents. Rather, this study aimed to examine subclinical changes in kidney or liver parameters associated with fluoride exposure among a generally healthy population. For example, the lowest GFR estimated in this study was 84 mL/min/1.73m2, and therefore none were below the<75 mL/min/1.73m2 value considered reflective of
abnormal kidney function. Future prospective studies including participants with and without kidney disease are needed to assess clinical changes in kidney or liver function.”
So, this study just could not have identified factors causing kidney and liver disease, let alone confidently attribute a cause to the disease. So we can reject the anti-fluoride activist’s claims and their misrepresentation of the study results.
But why all this fuss about fluoride?
Because the authors have a preoccupation with fluoride they used statistical analyses to see if they could find any association between drinking water fluoride or blood plasma fluoride and the measured kidney and liver parameters. They did find a small number of very weak associations.
They do not support the claims made by anti-fluoride activists so details of their results and a critique of their results are irrelevant to the main arguments. But I do have a hangup about the way statistical analyses are used, and the way they are over-interpreted to support pet biases so will discuss their data below.
Very few associations found
The study included nine kidney and liver function test parameters. Only one of these (Blood Urea Nitrogen [BUN]) had a statistically significant relationship with water fluoride (Uncorrected p <0.001) – see figure below.
The relationship of BUN with blood plasma F was also statistically significant (Uncorrected p <0.001) – see figure below.
The Standard Reference Range of BUN for this adolescent population is 6–23 mg/dL. Only a few data points are outside that range and they mainly occur for low water F or plasma F concentrations.
The authors also reported statistically significant associations of estimated glomerular filtration rate (eGFR) and Serum uric acid (SUA) with blood plasma F. However, once adjustments were made for plasma cotinine levels (a biomarker of tobacco smoke exposure) associations were not statistically significant (uncorrected p=0.18 for eGFR) or only “marginally” statistically significant (uncorrected p=0.06 for SUA).
In effect, statistically significant associations with either water F or plasma F occurred for only one. It is not credible for FAN to use these associations as indicators “that fluoride at commonly experienced doses can damage the kidneys and livers of adolescents.”
Reported associations may be “a pure act of will”
The authors appear to place a lot of reliance, in my opinion far too much reliance, of p values as somehow providing a causal mechanism behind the reported associations. This reliance has been strongly criticised by statisticians. Recently Briggs (2019) (Everything Wrong with P-Values Under One Roof) concluded:
“P-values should not be used. They have no justification under frequentist theory; they are pure acts of will. Arguments justifying p-values are fallacious. P-values are not used to make all decisions about a model, where in some cases judgment overrules p-values. There is no justification for this in frequentist theory. Hypothesis testing cannot identify cause. Models based on p-values are almost never verified against reality. P-values are never unique. They cause models to appear more real than reality.”
He goes on to elaborate:
“a small p-value has no bearing on any hypothesis . . . Making a decision about a parameter or data because the p-value takes any particular value is thus always fallacious . . . . Decisions made by researchers are often likely correct because experimenters are good at controlling their experiments, . . . . . ., but if the final decision is dependent on a p-value it is reached by a fallacy. It becomes a pure act of will.”
I believe Malin et al., (2019) place too much reliance on the p values they obtained and should have provided more complete results from the statistical analyses. Citing and relying on p values alone is, I believe, a major deficiency in this paper.
To their credit, while not providing full statistical analysis results the authors did display individual data points in their figures 1 and 2. This enables careful readers to make some judgments about the statistical analyses which would not be possible if the figures had not been provided.
Problems with outliers
The figures show a small number of outlying data points with some of the parameters. One has to be very careful that any association found only has a low p-value because of the influence (or leverage) of these outliers. The figures above for the BUN parameter illustrate the problem – particularly for water F where 2 data point greater than 6 mg/L clearly have a lot of influence.
This problem should stand out to any informed reader of the paper. The authors claim “Cook’s distance estimates were used to test for influential data points; none were identified.” However, this does not seem credible (particularly for Water F) so it is understandable that I should ask to see the results of these estimates so I can make up my own mind. They were not provided.
The associations were extremely weak
There is a huge scatter in the data points obvious in the figures above. This tells us that the reported associations can explain only a small amount of the variance. This is one reason why p-values alone can be misleading. A low p-value for an association (or fitted line) explaining only a few percent of the variance is meaningless. Concentration on such associations means that more important ones (explaining more of the variance) may be ignored. It also ignores the fact that the risk-modifying factor (in this case water F or plasma F) may simply be acting as proxies for more important factors (see Perrott 2018 for an example of this).
Malin et al., (219) should have provided more complete statistical analyses results to help readers judge the strength of the reported association. however, the figures themselves enable us to conclude the associations are very weak.
It is misleading to use the statistical result predictively
Malin et al., (2019) appear to “predict” the effect of fluoride on liver and kidney parameters, particularly BUN. They write in their abstract:
“A 1 mg/L increase in water fluoride was associated with a 0.93 mg/dL lower blood urea nitrogen concentration (95% CI: −1.44, −0.42; p=0.007)”
And
“1 μmol/L increase in plasma fluoride was associated with . . . . . a 1.29 mg/dL lower blood urea nitrogen concentration (95%CI: −1.87, −0.70; p < 0.001).”
But consider going from 0 to 1 mg/L in the image above for water F. The fitted line suggests that BUN would drop from about 11 to about 10 mg/dL. Taking the 95% CI interval into account the line “predicts” a value in the range of about 9.56 to 10.58 mg/dL. But only a small number of the points scattered at about 1 mg/L F have values in that range.
[Yes, I know. The authors only refer to associations, but reports of this work in the alternative health media are using these statements as predictions and that is how activists are suing the information.]
All that the best fit line can predict are values which fit the line. As the association represented by the best-fit line explains only a very small percentage of the variance (despite the small p-value) these “predictions” are meaningless. Unfortunately, the authors do not make this clear in their paper and this deficiency only contributes to the ability of anti-fluoride activists to misrepresent the findings.
Conclusions
Anti-fluoride activists are misrepresenting the finding reported in this paper. The authors themselves stress that their study was not designed to determine if fluoride exposure is associated with, or causes, declines in kidney or liver health. The FAN claim that the study shows“that fluoride at commonly experienced doses can damage the kidneys and livers of adolescents” is completely incorrect.
That is all we need to know regarding the way activists are misrepresenting the study. However, a closer look at the data suggests that the associations with fluoride for healthy individuals reported in the paper are extremely weak.
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Open Parachute 
Outstanding, Ken!! Exactly what has been needed with this thing!
Steve
Steven D. Slott, DDS Burlington, NC. 27216
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Ken and Steven,
I am slowly beginning to understand your reasoning.
If a patient/person takes a contaminant/poison and falls over dead or gets very sick, we would all agree they were harmed. Right?
If a patient has clinical symptoms (rash, fever, vomiting, damage to skin, teeth, bones, kidneys brain, etc.) of harm, would you agree or disagree they were harmed? I think you would agree, although we may disagree on the degree of harm.
If a patient has measured negative changes, sub-clinical, to their body chemistry and/or physiologic function, would you call that harm?
You quote the authors, “Rather, this study aimed to examine subclinical changes in kidney or liver parameters associated with fluoride exposure among a generally healthy population.”
Of course healthy cohorts should be used for sub-clinical measurements. I would agree with the authors.
In simple terms, I consider anything which reduces my body optimal function to be harmful. For example, I may not notice my blood pressure go up when I get angry, but if it does, I would call that harmful and I should avoid getting angry.
Another example, if I ingest too much fluoride and have reduced kidney function (sub-clinical), I would call that harmful. Add other kidney problems and I could develop clinical symptoms and it progress to kidney failure.
The authors reported negative changes in kidney function. Would you agree the negative changes are harmful? Or good/healthy? Or makes no difference?
Do you have any friends with kidney problems? Would they choose to take fluoride knowing ingesting fluoride as an adult would have no benefit and lower their kidney function? I would say for them a reasonable person would agree fluoride would be harmful and intake should be reduced.
Bill Osmunson DDS MPH
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Ken,
Let me use another well know example.
For many years tobacco smoking was actually promoted by health care providers to reduce clinical symptoms of disease. I took over a practice from a dentist who promoted tobacco smoking to reduce gum disease. Health care providers promoting tobacco did not look at sub-clinical warnings.
It took many years for governments to prohibit smoking in airlines and restaurants. Sub-clinical signs of second hand smoke were not considered.
For years, lead was added to petrol to reduce premature ignition and lead was added to paint to improve longevity. Sub-clinical signs were not considered.
Sub-clinical signs are very important and can show where a person’s body is under physiologic strain.
Dental fluorosis is a clinical sign of excess fluoride exposure. Sub-clinical signs of excess fluoride are being discovered, such as effect on mitochondria, kidney function, melatonin production, urine fluoride, etc.
Depressed physiologic function is harm.
Bill Osmunson DDS MPH
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Bill, you desperately search for confirmation of your bias from this paper but in doing so ignore simple facts.
For most of the parameters, studied the values were within the standard range. I commented on the fact that a small number of values were outside the standard range with the BUM parameter. Interestingly, this seems to have nothing to do with fluoride.
Like any clinical test, there are a standard set of values considered normal. If one is concerned about changes in values then it would be sensible to consider lifestyle factors one could possibly change. But based on these results one would be foolish to think any important risk factor had anything to do with fluoride.
Care to estimate the contribution made by fluoride to the variance in BUN values? Care to consider the effect of outliers on that? And also care to comment on the fact that this minuscule association was observed for only one of the 9 parameters considered?
A sensible approach to managing one’s health must surely involve not beeing fooled by ideologically motivated people like you promoting their own version of snake oil.
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A couple of thoughts that may be applicable…
In all of the time spent in my health career in NZ (since the 1970s…) I have never been able to routinely request BUN as a test from any medical laboratory. It may have been available as a “send-away” test, but I’ve never needed to even inquire about it. I wasn’t even taught about BUN in medical school!
BUN is a somewhat obsolescent measure of kidney function that the USA still seems to cling to whilst most of the rest of the world has left it behind. There are too many factors that can influence BUN, which means it is a much less specific indicator of kidney function than the combination of creatinine and urea measurements are.
In healthy adolescents, such as those that comprised this study, BUN is more a measure of protein catabolism and ingestion than a specific measure of kidney function. In other words, the results from those outliers may be more representative of their last meals, or maybe of their sporting activites, than of their renal function.
Using creatinine levels for this research, rather than BUN, would likely have removed the outliers from the research and therefore given the anti-fluoridationists nothing to comment about.
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“Anti-fluoride activists misrepresent . . . ” — so the headline goes. More accurate might be: : ‘Open Parachute misrepresents FAN scientists’ summary of fluoride liver/kidney study.’
The FAN authors do not try to claim that the study found fluoride exposure to cause frank, clinical kidney or liver disease. But your opening paragraphs clearly try to lead your reader to that conclusion. The study was about, and the FAN authors faithfully stuck with that, low to mid-level, long-term fluoride exposure being associated with changes in function (reduced function) in a population not currently diagnosed with liver or kidney disease. That is every bit as important as simply studying people with advanced disease. In fact it can be argued that it is of utmost importance to study issues that lead to better directions in PREVENTION than to focus entirely on those with active or advanced disease.
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David, FAN claimed the study indicated “that fluoride at commonly experienced doses can damage the kidneys and livers of adolescents.”
It does nothing of the sort.
Nor does the article deal “with changes in function (reduced function)” It simply shows there is a range of values for the parameters – hardly surprising. Only one parameter in the 9 investigated shows a statistical association with fluoride but that association is extremely weak and in itself likely false because of outliers.
Values for BUN outside the standard recommended range appear to have nothing to do with fluoride.
Please read my article.
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Ken—I read your article, and hence my recommendation for a change to the heading.
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David, your recommendation is obviously rejected. You have been unable to justify it.
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