McPherson 2018 - Comments on the NTP Study

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McPherson 2018 - Comments on the NTP Study

Postby admin » Sat Jun 13, 2020 8:23 am

    McPherson CA, Zhang G, Gilliam R, Brar SS, Wilson R, Brix A, Picut C, Harry GJ - "An Evaluation of Neurotoxicity Following Fluoride Exposure from Gestational Through Adult Ages in Long-Evans Hooded Rats" Neurotox Res 34(4):781-798 (2018) doi: 10.1007/s12640-018-9870-x. Epub 2018 Feb 5. PMID: 29404855; PMCID: PMC
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077107/

Comments: (June 13, 2020, updated July 7, 2020)

This study was done by scientists of the US National Toxicology Program (NTP), supposedly "to address issues identified in the NTP systematic review (NTP 2016) of determining low to moderate levels of evidence for effects of F− exposure on learning and memory and to address the paucity of quality studies conducted at exposure levels near the recommended level for community water fluoridation in the USA."

When one reads through this paper (as well as the other publications on this matter since 2016 by the NTP) one gets the distinct impression that this study was specifically designed to avoid showing the adverse effects of fluoride.

Background

This was a study to evaluate the neurotoxicological effects of fluoride.

As neurodevelopment is closely tied to thyroid function, thyroid hormones were to be evaluated, together with TSH, the thyroid-stimulating-hormone.

Thyroid hormones control brain development.

    Thyroid hormone deficiency at critical stages during pregnancy and early childhood results in impaired development of the brain and consequently in impaired mental function. The WHO still considers iodine deficiency, which leads to hypothyroidism, the SINGLE most important preventable cause of brain damage worldwide (Moog et al., 2017; WHO, 2007). An adequate supply of iodine to children and pregnant women is considered a basic human right (Pedraza et al., 2006).

    The most vulnerable groups are pregnant and lactating women and their developing fetuses and neonates (Moog et al., 2017). As is the case in fluoride toxicity, the severity and irreversibility of thyroid hormone deficiency in humans depends on both the degree of the deficiency and the period during development in which it is suffered (Pedraza et al., 2006).

    It is now established that even mild changes in thyroid function in prenatal life can have lasting negative consequences for a child’s development, and be associated with lower full IQ scores, and impaired motor- and neurological function in childhood (Päkkilä et al., 2015; Li et al., 2010; Haddow et al., 1999; Kooistra et al., 2006).

    Numerous high risk windows during pregnancy have been identified. Maternal deficiency in thyroid hormone during the first trimester can result in adverse effects on a child’s intelligence and motor development (Li et al., 2010; Kooistra et al., 2006), and be a risk factor for both verbal and nonverbal cognitive delay in early childhood (Henrichs et al., 2010).

    Other studies have shown that children of healthy women who had very high TSH concentrations in the 17th week of pregnancy had significantly lower IQ levels at the age of 7-9 year (Haddow et al., 1999) and that the IQ in these children was inversely correlated with maternal TSH concentration (Klein et al., 2001).

    The number of children at risk for neurodevelopmental deficits related to early maternal thyroid hormone deficiency is 150–200 times greater than that of newborns with congenital hypothyroidism, for which successful screening programs have been instituted in many countries (Lavado-Autric et al., 2003).

    More than 15% of women of child-bearing age in the United States are reported to have maternal thyroid hormone deficieny (Hollowell & Haddow, 2007; Perrine et al., 2010).

Many studies on humans and animals have shown that fluoride may cause identical blood thyroid hormone panels as are normally observed in iodine deficiency. Some of these studies were included in the 2016 NTP literature review (i.e. Susheela et al, 2005). Animal studies have documented that the damage observed in the actual thyroid gland resembles the one observed in iodine deficiency. The vast amount of research showing that fluoride may cause goiter - the name given to the enlarged thyorid gland observed in iodine deficient areas - dates back almost 150 years (PFPC 1996). For over 30 years, fluoride was used as an antithyroid medication in Germany and other countries, specifically for the treatment of "Basedow" disease - the name given to hyperthyroidism when it is caused by excessive iodine intake. See: https://poisonfluoride.com/History/history_0.html

Rats

Rats are usually chosen to investigate the effects of maternal thyroid hormone deficiency on brain development because, like humans, rats have a period early in development where they are wholly dependent on thyroid hormone provided by the mother. The human first trimester-equivalent covers much of the prenatal period in a rat. At gestation day 7 (GD7), rodent embryonic stages are consistent with those in the human 3rd week post-fertilization (Sulik et al., 1981). Because a large part of brain maturation in rodents happens after birth, it is thought that the early postnatal period in rats mimics the last trimester in humans. Postnatal day 21 (PND21) in rodents is considered the equivalent to a child 2-3 years old (Semple et al., 2013).

Did the NTP test for thyroid hormones and TSH?

Yes, ONCE. Male rats only (!) were tested once - at PND56 (late adolescence, young adulthood). More on the actual tests below. What is astonishing here - besides the selections of gender and test date - is that no efforts were made to evaluate thyroid hormones in serum or brain at the crucial times of development. None. Pregnant dams were not tested at all.

When the serum thyroid hormone levels were evaluated, fluoride levels were not tested at the same time. Those were done on adult rats only, presumably >PND90. The actual date is unclear from the information supplied. How can this be considered appropriate? No serum levels are available from PND25, when brain and femur were investigated.

Before we discuss the thryoid tests a bit further below, a few words on the iodine in the rat feed. Iodine is essential for the formation of thyroid hormones.

Iodine in the Feed

While the amount of fluoride in the chow was considered in this study (as fluoride toxicity depends on TOTAL intake), the iodine content was not. It is very hard to understand how the top toxicologists in the US could possibly commit such a blunder - while conducting an neurotoxicity assessment involving thyroid function. This matter becomes even more worrisome when one considers that there are many hundreds of studies showing the antagonistic relationship of fluoride and iodine, including over 200 reports from China alone (PFPC, 2007). The NTP was made aware of all these studies BEFORE this experiment started (PFPC, 2016).

However - that is not all. Instead of using the regular NTP-2000 rodent chow that is normally employed in NTP toxicity assessments, McPherson et al. actually chose a chow with iodine content of 6 mg/kg, over 25 times the amount that is in the standard NTP-2000 rodent chow, reported to be 0.2 mg/kg (NTP, 2016). [3rd party vendors of the NTP-2000 chow list an iodine content of 0.33 mg/kg (Zeigler), far below 6 mg/kg.]

With iodine intake this high it requires much more fluoride to produce similar effects as is observed with a normal iodine intake. Fluoride toxicity is directly related to iodine and thyroid status. For an iodine-deficient person/animal, far less amounts of fluoride are toxic (Lin Fa-Fu et al., 1991; Guan et al., 1988; Zhao et al., 1998).

Obvious questions: Why was the standard NTP-2000 rat chow not used? Why was a chow selected with such high iodine content? Why was there no accounting for iodine in the diet?


Animal Model

Looking now at the rat strain used in this study, one can see a pattern emerging - a pattern to deceive, most regrettably.

McPherson et al. used Long-Evans rats in their study. Besides the work by Varner et al. (1994; 1998) we know of no other study reviewed by the NTP that used this rat model. Out of the many China studies, for example, not one animal study used Long-Evans rats, but rather other, established, strains in toxicology. The studies reviewed by McPherson et al. were all done on either Wistar or Sprague Dawley (SD) rats.

    NOTE: Since the 1930s it has been known that there are differences in Long-Evans rats when it comes to the thyroid (Freudenberger, 1932). Long-Evans rats are known to have a lower sensitivity to iodine deficiency - it takes higher amounts and a longer exposure time to anti-thyroid agents to produce similar effects as in other rat species (Ruiz et al, 2013; Gilbert et al., 2011; Okamura et al., 1981). Changes in thyroid hormone levels in Long Evans rats do not result in the same magnitude of changes in serum TSH as they do in albino rats (Gilbert et al., 2011). The normal TSH level in a Long-Evans rat is almost twice as high as that of a Sprague-Dawley rat (Rybnikova et al., 2018). It has been alleged that the NTP was aware of the higher resistance of Long-Evans rats to fluoride poisoning (Spencer & Limeback, 2018).

    Considering the other tests employed in this study: it has been documented in the past that Long-Evans rats perform better in motor tasks than other strains (Yanai, et al., 1979), which of course is not surprising when one considers the lower sensitivity to iodine deficieny. Other studies have shown that standard behavioral assays with Long-Evans rats do not readily detect the neurotoxicity induced by modest developmental thyroid hormone deficiency (Gilbert et al., 2013).

So, the big question is: why was a rat strain, known for having a reduced sensitivity to iodine deficiency, chosen for this study on fluoride - a toxin known by the NTP to cause effects similar to iodine deficiency? In a study on neurological development which is under control of thyroid hormones? This doesn't make any sense.

Thyroid Tests - Methods

As mentioned above, there are no data on thyroid hormone or TSH levels at the beginning or the end of the experiment, in pups, pregnant dams, nor any female rat.

There is only data on male rats from PND56, a day long after the crucial risk periods. No conclusions can be drawn if those levels are elevated or reduced compared to prior or later levels, as those tests were not conducted. No reference levels are given for normal values in Long-Evans rats.

As is apparent from the paper's table 3 - McPherson et al. did not evaluate Free T3 (FT3) and Free T4 (FT4), but Total T3 and Total T4. Values are reported in ng/dl for T3 and μg/dl for T4, indicating that free fractions were not investigated. FT3 is normally indicated in pg/dl, FT4 in ng/dl. The free (unbound) hormone is the biologically active one.
https://www.ncbi.nlm.nih.gov/pmc/articl ... able/Tab3/

    SIDENOTE: The free thyroid hormones should always be measured in fluoride investigations. The levels of Total T3 or Total T4 do not reflect the true extent of fluoride disruption of thyroid hormone metabolism. Fluoride interferes with deiodinase activities, which results in an increase of rT3 (made from Total T4). rT3 is a biologically inactive form of T3, crucial during the times of gestation, as it is involved in all timing aspects in neurodevelopment. Fluoride-induced increases in rT3 levels - even at low concentrations - have been well documented, leading to the suggestion that rT3 be used as a biomarker in fluoride poisoning (Lin Fa-Fu et al., 1991; 1992; Sashi & Singla, 2013). During gestation it is FT4 and TSH that need to be measured, at a minimum. In humans even a slight deficiency in FT4 ("hypothyroxinemia") during the first trimester can have serious adverse consequences. This is why trimester-specific reference intervals for TSH and FT4 levels in pregnant women have been issued in guidelines to reduce the risk of brain damage (Stagnarro-Green et al., 2011).

It is important to note that the NTP also failed to differentiate between studies investigating total vs free fractions in their 2016 literature review, as well as in the 2019 Draft. Studies are simply lumped together, without any apparent understanding on the matter.

The test used by McPherson et al. to assess TSH levels in this study was the Rat Pituitary Magnetic Bead Panel Kit. While this test might be efficient - we have no idea - we know of no other study reviewed by the NTP that has used this method. As a matter of fact, we don't know of ANY study investigating fluoride effects on TSH that has used this test. Again, no reference levels are given.

No information is given if the authors conducted even a basic test method validation, or why this test was chosen.

Thyroid Hormone - Test Results

McPherson et al. claim that T3, T4, and TSH levels "were not altered as a function of 10 or 20 ppm F− in the drinking water". They have no right to come to this conclusion as they did not conduct a proper investigation, far from it.

It is also not true, based on the very limited data that is available from PND56.

When the TH data supplied by McPherson et al. in Table 3 is closer investigated, one can clearly identify a pattern showing that T3 levels rise with increasing fluoride intake from Group 2 through to Group 4, while TSH levels slightly decrease. The T3/T4 ratio rises with increasing fluoride intake.


This is consistent with data on fluoride effects in areas where iodine intake is sufficient or excessive. An increase in the T3/T4 ratio is normally seen as a sign of mild thyroid insufficiency, representing an autoregulatory adaptive response of the thyroid, augmenting the relative synthesis and release of T3 over T4 (Pedraza et al., 2006). The group with the high fluoride content in the feed (G1) has significantly elevated TSH levels, the diagnostic sign of hypothyroidism.

However, as McPherson et al. do not supply any reference ranges, or any information as to how the TSH test method used compares to regular methods, results must be interpreted with great caution. The mean TSH, T4 and T3 levels in this study differ greatly from reports on Long-Evans rats in the literature (Rybnikova et al., 2018; Gilbert et al., 2011; Nishimura et al., 2003). For example, in Nishimura's study mean T4 levels in Long-Evans rats at approximately similar ages were 3.7 ug/dl, while in this study they are almost twice as high. Similarly, in Gilbert's study on iodine deficiency in Long-Evans rats, the control rats on normal iodine intake at PD56 had a T4 of 3.8 ug/dl, a T3 of 100 ng/dl, and a TSH of 1.3 ng/ml. In this study all the values are higher, in all fluoride groups.

Further it is important to remember that these results are from PND56 only. In rodents, as in humans, effects of fluoride upon thyroid hormones depend on dose, time and duration, just like in iodine deficiency. For this reason, rodent studies on thyroid hormones in brain development often include TH assays during gestation, as well as numerous crucial time points in the post-natal period (i.e. Gilbert et al., 2013; van Wijk et al., 2008).

While often there is at first a stimulation of thyroid hormone production by fluoride, at higher doses and/or longer duration it turns to inhibition (Zhao et al., 1998). This is the same effect that TSH has upon thyroid hormone metabolism. Fluoride is a TSH analogue (Jenq et al., 1993; PFPC 2003).

Thyroid Gland

A general pathology examination was conducted on the heart, kidney, liver, testes, epididymides, prostate, and seminal vesicles - but NOT the thyroid. Why not? Was this not a study involving thyroid function? Thyroids were not even weighed or measured. Thyroid weight increase in iodine deficiency is caused by increased TSH levels resulting in the excessive stimulation of the gland. As mentioned above, fluoride is well-known to cause enlarged thyroids and increase thyroid weight in humans and rodents (PFPC 1996, Zhao et al. 1998, 1989; Li et al., 2011).

Amounts of Fluoride Used

McPherson et al. state:

"In the current study, the top dose of 20 ppm F− was selected based upon the US Environmental Protection Agency’s Maximum Contaminant Level of 4 ppm and the conventional wisdom that a 5-fold increase in dose is required to achieve comparable human serum levels (Dunipace et al. 1995; NRC 2006)."


This has been an issue ever since the NRC published their review of the EPA's MCL standards in 2006. It is based on false assumptions. The very fact that fluoride in water levels for rodents must be 10 to 20 times higher - not just 5 times - than those for humans to produce the condition of dental fluorosis is a clear example as to how wrong this "conventional wisdom" is (Bronckers et al., 2009). In the present study only the concentration of 20 mg/L in water (plus the F- in the chow) caused mild DF in adult rodents. This is 20 to 40 times higher than the F- in water amount known to cause dental fluorosis in humans. In the study by Lin et al. (1991) on iodine-deficient children, fluoride in water at 0.34 mg/L caused dental fluorosis. The obvious conclusion from this study is that Long-Evans rats require 20 to 40 times the amount of fluoride in water to produce similar dental defects as are observed in children.

The authors further fail to explain why adults rats, drinking fluoridated water at 10 mg/L, have higher fluoride serum levels than those drinking water at 20 mg/L, raising additional concerns.

See Table 2: https://www.ncbi.nlm.nih.gov/pmc/articl ... able/Tab2/

Closing Comments

While others have lauded this study for its implementation of systematic review principles, that whole discussion is rather pointless as the study was done incorrectly as a toxicological evaluation. There are way too many serious flaws here to consider them just a coincidence, or mere incompetence.

The NTP 2016 Review or 2019 Draft did not address ANY of the Chinese studies that evaluated fluoride effects on thyroid hormones in rodents, and compared to brain development - including those that investigated effects in pregnant dams and their offspring. Why? These studies were listed in our 2016 submission. But this heavily flawed study by McPherson et al. - a study that doesn't satisfy even the most basic requirements for a toxin/thyroid/brain investigation - is now considered THE best animal study on this subject available? There is something very wrong with this picture.

This paper should be withdrawn. A work like this should never be allowed to influence public health policy.

Fortunately, there are many studies appearing from all over the world documenting the adverse effects of fluoride on thyroid hormone metabolism, in humans and animals. More than 150 papers from the last 15 years can be accessed from our website - viewtopic.php?f=7&t=1345 (PFPC 2020). It is only a matter of time until the evidence will simply become too overwhelming to ignore and deny. We can only hope that the US public health agencies such as the NTP, the ATSDR, and the CDC will be held accountable for having suppressed the truth - knowingly - for so many years.

PFPC Canada, 2020

© 2020 PFPC
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Appendix H, Ingredients in NTP-2000 Rat and Mouse Ration

Postby admin » Sun Jun 14, 2020 11:18 pm

Appendix H, Ingredients, Nutrient Composition, and Contaminant Levels in NTP-2000 Rat and Mouse Ration

Cover of NTP Technical Report on the Toxicity Studies of Sodium Thioglycolate (CASRN 367-51-1) Administered Dermally to F344/N Rats and B6C3F1/N Mice
NTP Technical Report on the Toxicity Studies of Sodium Thioglycolate (CASRN 367-51-1) Administered Dermally to F344/N Rats and B6C3F1/N Mice: Toxicity Report 80 [Internet].
National Toxicology Program.
Research Triangle Park (NC): National Toxicology Program; 2016 May.

https://www.ncbi.nlm.nih.gov/books/NBK551148/
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TSH Levels in Pregnancy

Postby admin » Mon Jun 15, 2020 11:00 am

To reduce the risk of abnormal brain development, a TSH of 2.5 mIU/L is the upper limit of normal for TSH in the first trimester in official guidelines.

Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, Nixon A, Pearce EN, Soldin OP, Sullivan S, Wiersinga W; American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum. - "Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum" Thyroid 21(10):1081-125 (2011)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472679/
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Actual Results of thyroid levels in McPherson et al.

Postby admin » Mon Jun 15, 2020 5:30 pm

When results are analyzed one can see a clear pattern in groups G2 to G4: as fluoride doses are increased there is a gradual increase in T3, while TSH levels are reduced - which is not surprising considering the large amounts of iodine - but this is valid for PND56 only. Because thyroid tests were not done earlier or at any other time during the investigation, one can't draw any conclusions at all. Where levels elevated at the beginning of the study? Reduced? As has been documented in countless studies investigating fluoride effects on the thyroid in rodents, the effects of fluoride change with dose and duration of exposure, and that prolonged exposure is a key factor (Li et al., 2013; Zhao etal. 1998; 1992). At these levels of fluoride exposure (10 and 20 mg/l), others have documented at first an increase in TSH levels at 2 months, then a decrease. This is in line with many other studies done on both fluoride and TSH effects on the thyroid in rodents. For the researchers to not measure TH and TSH at different intervals of the study is simply inexcusable.

TABLE 3
https://www.ncbi.nlm.nih.gov/pmc/articl ... able/Tab3/

Liu Hongliang, Yu Linyu, Cui Yushan, Zeng Qiang, Zhao Liang, Hou Changchun, Wang Aiguo - "Influence of Long Term Excessive fluoride Intake on the Morphology and Function of Thyroid in Rats" Environmental Health 3(5):390-393 (2013)
http://www.hjwsxzz.com/Magazine/Show.aspx?ID=52248

Zhao W, Zhu H, Yu Z, Aoki K, Misumi J, Zhang X - "Long-term Effects of Various Iodine and Fluorine Doses on the Thyroid and Fluorosis in Mice" Endocr Regul 32 (2):63-70 (1998)

Zhao WY, Zhu HM, Gao YZ, Qin L, Chen CY, Xu DQ - "The study of iodine and fluorine combined action on experimental goiter and fluorosis" J Chinese Endemic Diseases, Prevention and Treatment (7):16-18 (1992)
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Inflammation in the prostate

Postby admin » Mon Jun 15, 2020 7:10 pm

McPherson et al. report that there was an increase in inflammation of the prostate. Studies on humans have shown that there is a significant relationship between FT4 levels and markers of prostate hyperplasia in men (Lee et al., 2019). As stated, FT4 levels were not measured by McPherson et al..

Lee JH, Park YW, Lee SW - "The Relationships between Thyroid Hormone Levels and Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia" World J Mens Health 37(3):364-371 92019) doi: 10.5534/wjmh.180084. Epub 2019 Jan 4. PMID: 30644234; PMCID: PMC6704305
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Re: McPherson 2018 - Comments on the NTP Study

Postby admin » Wed Jun 17, 2020 3:32 am

Other rat chow data sheets, for comparison - normally around 1 mg/kg

LabDiet/Purina 5001:
http://www.labsupplytx.com/wp-content/u ... 0/5001.pdf
SDS RM3-E-FG:
http://www.sdsdiets.com/pdfs/RM3-E-FG.pdf
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A proper study....

Postby admin » Wed Jun 17, 2020 9:29 am

If this would have been a proper study, designed in line with established protocols, there would have been thyroid hormone/TSH measurements done on pregnant dams, and the offspring at GD16 or GD20, in addition to PND14, PND21 and PND90 (see Gilbert et al., 2011). Time permitting, another date could have been added, such as PND150. For both males and females.

There would have been three different diets:

Iodine Deficient (ID)
Iodine Normal (IN)
Iodine Excessive (IE)

Thyroid hormones would have been tested not only in serum, but in brain, as is required in such investigations on TH/brain interactions, and compared to fluoride levels.

There are biologically based dose-response (BBDR) models to employ. The effects of iodine deficiency and anti-thyroid agents upon brain development in rodents have been studied extensively. If Long-Evans rats are to be used, a BBDR has been developed for this rat strain by scientists from the FDA and the EPA's Toxicity Assessment Division, adjusted for the difference in iodine sensitivity (Gilbert et al., 2011; 2013; Fisher et al., 2013).

In an ideal study, rats should be exposed for numerous weeks before breeding (Gilbert et al., 2013; 2011).

Fisher JW, Li S, Crofton K, Zoeller RT, McLanahan ED, Lumen A, Gilbert ME - "Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model" Toxicol Sci 132(1):75-86 (2013)
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An essential nutrient?

Postby wendy » Thu Jun 18, 2020 1:29 am

Comment:

I just noticed that McPherson et al. state that "fluoride is considered an essential nutrient in the diet."

It is not.

Please see my post from 2013, with all documentation:
viewtopic.php?f=42&t=762

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More on the T3/T4 ratio

Postby doctorJ » Thu Jun 18, 2020 9:03 am

Wendy - a few notes here, re: T3/T4 ratio

All my comments are about free T3 (FT3) and free T4 (FT4), not TT3 or TT4.

The ratio of serum FT3 to FT4 is normally constant in healthy children and adults (Oto et al., 2017). When the free thyroid hormones are meant, a rise in FT3 is often seen as an indicator of increased deiodinase 2 (D2) activity, so it is extrathyroidal - not coming from the thyroid (see Oto et al., 2015; Park et al., 2017). FT3/FT4 ratios are considered a surrogate measure of peripheral deiodinase activity (Haddow et al., 2019).

As fluoride is a TSH analogue, it would cause increased D2 activity in extrathyroidal tissue. In children, elevated TSH levels lead to an increase in the FT3/FT4 ratio, up until the age of 40 (Strich et al., 2016). As TSH levels are going down in this study, it appears to be that fluoride is doing the extra conversion, not TSH. It might depend on iodine intake, and as you point out, there appears to be very high iodine intake from the rat diet in the NTP study. There are studies on fluoride effects on D2 from China, on children and rats. I will try to find them. All the papers below are in our database.

In humans, an elevated FT3/FT4 can also seen as sign of a hyperthyroid condition called thyrotoxicosis, but is usually accompanied by low TSH levels.

The FT3/FT4 ratio is associated with increased risk of a condition called "metabolic syndrome" and insulin resistance (Park et al., 2017; Urrunaga-Pasto et al., 2019). Insulin resistance is increased even at low "optimum" levels of fluoride (Szczuko et al., 2019). It is also associated with cardiovascular disease (Yu et al., 2018) and cancer.

Chen X, Zhou Y, Zhou M, Yin Q, Wang S - "Diagnostic Values of Free Triiodothyronine and Free Thyroxine and the Ratio of Free Triiodothyronine to Free Thyroxine in Thyrotoxicosis" Int J Endocrinol 2018:4836736 (2018)

Del Buono A, d'Orta A, Licito A, et al. - "Age-related FT3/FT4 ratio as possible indicator of chronic disease and cancer development: a pilot study" World Cancer Research 4 (4): e970 (2017)

Gu Y, Li H, Bao X, Zhang Q, Liu L, Meng G, Wu H, Du H, Shi H, Xia Y, Su Q, Fang L, Yu F, Yang H, Yu B, Sun S, Wang X, Zhou M, Jia Q, Guo Q, Chang H, Wang G, Huang G, Song K, Niu K - "The Relationship Between Thyroid Function and the Prevalence of Type 2 Diabetes Mellitus in Euthyroid Subjects" J Clin Endocrinol Metab 102(2):434-442 (2017)

Gu Y, Chi VTQ, Zhang Q, Liu L, Meng G, Wu H, Bao X, Zhang S, Sun S, Wang X, Zhou M, Jia Q, Song K, Niu K - "Low-Normal Thyroid Function Predicts Incident Anemia in the General Population With Euthyroid Status" J Clin Endocrinol Metab 104(11):5693-5702 (2019)

Haddow JE, Metzger BE, Lambert-Messerlian G, Eklund E, Coustan D, Catalano P, Palomaki GE - "Maternal BMI, Peripheral Deiodinase Activity, and Plasma Glucose: Relationships Between White Women in the HAPO Study" J Clin Endocrinol Metab 104(7):2593-2600 (2019)

Le TN, Celi FS, Wickham EP 3rd - "Thyrotropin Levels Are Associated with Cardiometabolic Risk Factors in Euthyroid Adolescents" Thyroid 26(10):1441-1449 (2016)
https://pubmed.ncbi.nlm.nih.gov/27599541/

Nomura R, Miyai K, Kuge R, Okura T, Goto M, Hasegawa Y - "Free T3 to free T4 ratio less than 2.0 suggests low T3 syndrome rather than central hypothyroidism from the age of two to eighteen years" Endocr J 64(2):213-219 (2017)

Oto Y, Muroya K, Hanakawa J, et al. - "The ratio of serum free triiodothyronine to free thyroxine in children: a retrospective database survey of healthy short individuals and patients with severe thyroid hypoplasia or central hypothyroidism" Thyroid Res 8:10 (2015)

Park SY, Park SE, Jung SW, Jin HS, Park IB, Ahn SV, Lee S - "Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects" Clin Endocrinol (Oxf) 87(1):87-96 (2017)

Pasqualetti G, Schirripa M, Dochy E, Fassan M, Ziranu P, Puzzoni M, Scartozzi M, Alberti G, Lonardi S, Zagonel V, Monzani F, Loupakis F - "Thyroid hormones ratio is a major prognostic marker in advanced metastatic colorectal cancer: Results from the phase III randomised CORRECT trial" Eur J Cancer 133:66-73 (2020)

Strich D, Karavani G, Edri S, Chay C, Gillis D - "FT3 is higher in males than in females and decreases over the lifespan" Endocr Pract 23(7):803-807 (2017)

Strich D, Karavani G, Edri S, Gillis D - "TSH enhancement of FT4 to FT3 conversion is age dependent" Eur J Endocrinol 175(1):49-54 (2016)

Sun X, Liu W, Zhang B, Shen X, Hu C, Chen X, Jin S, Jiang Y, Liu H, Cao Z, Xia W, Xu S, Li Y - "Maternal Heavy Metal Exposure, Thyroid Hormones, and Birth Outcomes: A Prospective Cohort Study" J Clin Endocrinol Metab 104(11):5043-5052 (2019)
"The mediation analyses suggested that 5.33% to 30.57% of the associations among V, As, and Pb levels and birth size might be mediated by maternal FT3 or FT3/FT4 ratio."

Szczuko M, Splinter J, Zapałowska-Chwyć M, Ziętek M, Maciejewska D - "Fluorine may intensify the mechanisms of polycystic ovary syndrome (PCOS) development via increased insulin resistance and disturbed thyroid-stimulating hormone (TSH) synthesis even at reference levels" Med Hypotheses 128:58-63 (2019)

Tarcin O, Abanonu GB, Yazici D, Tarcin O - "Association of metabolic syndrome parameters with TT3 and FT3/FT4 ratio in obese Turkish population" Metab Syndr Relat Disord 10(2):137-42 (2012)

Urrunaga-Pastor D, Guarnizo-Poma M, Moncada-Mapelli E, Aguirre LG, Lazaro-Alcantara H, Paico-Palacios S, Pantoja-Torres B, Benites-Zapata VA. Insulin Resistance and Metabolic Syndrome Research Group - " High free triiodothyronine and free-triiodothyronine-to-free-thyroxine ratio levels are associated with metabolic syndrome in a euthyroid population" Diabetes Metab Syndr 12(2):155-161 (2018)

van den Berg EH, van Tienhoven-Wind LJ, Amini M, Schreuder TC, Faber KN, Blokzijl H, Dullaart RP - "Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects: the Lifelines Cohort Study" Metabolism 67:62-71(2017)

Wang P, DU R, Lin L, Ding L, Peng K, Xu Y, Xu M, Bi YF, Wang WQ, Ning G, Lu JL - "Association between Free Triiodothyronine Levels and Peripheral Arterial Disease in Euthyroid Participants" Biomed Environ Sci 30(2):128-133 (2017)

Yu T, Tian C, Song J, et al. - "Value of the fT3/fT4 ratio and its combination with the GRACE risk score in predicting the prognosis in euthyroid patients with acute myocardial infarction undergoing percutaneous coronary intervention: a prospective cohort study" BMC Cardiovasc Disord 18:181 (2018)
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Sugar Sugar - some history

Postby wendy » Fri Jul 17, 2020 12:02 am

I'd like to point out another study with Long-Evans rats that was done in the 1950s - also to hide fluoride effects upon thyroid function and to mislead the public.

That study was done by James Shaw from the Harvard Dental School. He and his colleague Auskaps conducted an experiment with sodium fluoride concentrations at levels of 1, 5 and 20 ppm in water. They used Long-Evans and Holtzman rats. Both of these strains are known to have a lower iodine sensitivity and respond poorly to iodine deficiency compared to other rat strains more commonly used, such as Wistar or SD rats.

    Some Background: Shaw was sponsored by the Sugar Research Foundation (as were Harvard Public Health nutritionists like Frederik Stare). He wrote articles for the Sugar Industry, downplaying the caries-causing effects of sugar, while praising the wonders of fluoride in reducing caries. This "thyroid-study" from 1954, with Auskaps, was financed by the Nutrition Foundation. [The Nutrition Foundation had been founded in 1941 by food manufacturing industry, including cereal companies, fruit and food manufacturers - many of whom had been dealing with great problems concerning spray residue from fluoride and lead-arsenate pesticides. The Sugar Research Foundation, the Sugar Association, Kellogg's, as well as pesticide and additive manufacturers also later became sponsors.]

    Stare was the founder of the Nutrition Department at Harvard. He was a well-known and often-quoted fluoridation promoter. He later became somewhat of a spokesperson for the sugar industry, representing Kellogg, Nabisco, and the Cereal Institute in the 1970s, "asserting that their products—which were up to 70 percent sugar—provided better nourishment for children than would an old-fashioned breakfast" (Hess, 1978). In the early 1970s Kellogg's donated $2 million to Stare's department. A study proclaiming that sugared cereals did not cause caries was later published by Shaw (Shaw, 1974). In the 1980s Kellogg's, through the Kellogg Foundation, became the main sponsor of the salt fluoridation program in South America (PFPC 2003).

An example of Shaw's work for the Sugar Research Foundation is available online:

Shaw JH - "Tooth Decay - An Evaluation of Current Theory" Researcher Finds New Evidence - Suggests Revision of Prevalent Acid Theory
Harvard School of Dental Medicine, in: The Sugar Molecule, Vol V, No 3 (1951) The Sugar Research Foundation
https://mountainscholar.org/bitstream/h ... sAllowed=y

Auskaps AM, Shaw JH - "Hemoglobin concentration, thyroid weight and growth rate in rats during minimum fluoride ingestion" J Nutr 55(4):611-21 (1955)
https://pubmed.ncbi.nlm.nih.gov/14368361/

Hess J - "Harvard's Sugar-Pushing Nutritionist" The Saturday Review, August 1978, pp. 10-14 (1978)
https://www.unz.com/print/SaturdayRev-1 ... /Contents/

PFPC - Kellogg's (2003)
https://poisonfluoride.com/pfpc/html/kellogg_1.html

THE NUTRITION FOUNDATION, INC - Science 95(2455):64 (1942)

Shaw JH - "Influence of cereal incorporation in a caries-producing diet on caries activity in rats" J Dent Res 53(2):397-401 (1974)
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