Goitre (aka goiter) is an enlargement of the thyroid gland that in some cases can produce visible swelling in the neck. The main cause of goitre is iodine deficiency. Goitre can also be caused by other things, including hypothyroidism and substances that cause goitre (goitrogens).
Since as far back as the 19th century, fluoride has been identified as a possible goitrogen. In the research to date, studies that have examined human populations with adequate intake of iodine have reported mixed results about fluoride’s ability to produce goitre. (NRC 2006; Burgi 1984; McLaren 1969). Where, however, the examined populations had either excessive iodine intakes, or deficient iodine intakes, the research has been more consistent in finding a goitrogenic effect from fluoride. (Gas’kov 2005; Hong 2001; Wang 2001; Xu 1994; Yang 1994; Lin 1986). Since most of this latter research was initially published in either Russian or Chinese and was only recently translated into English by the Fluoride Action Network, the NRC’s review of fluoride’s goitrogenic potential (e.g, NRC 2006) was not able to take this evidence into account. As such, the evidence linking fluoride to goitre is stronger than previously determined, at least for populations with excessive, or deficient, exposure to iodine.
Origins of the Fluoride/Goitre Connection:
Fluoride was first suspected to be a goitrogen in 1854, when Maumeme reported producing goitre in a dog after 4 months of daily fluoride exposure (9 to 55 mg/day). Based on this and subsequent research in the early 20th century, doctors in Europe and South America began using fluoride as a medical treatment for hyperthyroidism (over-active thyroids). (McLaren 1969). As a goitrogen, doctors believed fluoride could suppress the thyroid’s function and thereby alleviate symptoms in people with overly active thyroids. Subsequent clinical research found merit in this idea, as a daily fluoride treatment of just 2 to 5 mg/day was found capable of reducing thyroid function in a group of hyperthyroid patients. (Galletti & Joyet 1958). Ultimately, however, more effective treatments were discovered and the use of fluoride was phased out by the 1960s. (Merck Index 1968).
Fluoride & Goitre in Humans:
Throughout the 20th century, various research teams investigated the relationship between fluoride in water and the incidence of goitre. As discussed by the NRC, the results of these studies have been mixed, with some studies finding a significant relationship, and others finding no relationship. (NRC 2006). As summarized by the NRC:
“Three studies illustrated the range of results that have been reported: (1) Gedalia and Brand (1963) found an association between endemic goiter in Israeli girls and iodine concentrations in water but found no association with fluoride concentrations (<0.1-0.9 mg/L). (2) Siddiqui (1960) found goiters only in persons aged 14-17 years; the goiters, which became less visible or invisible after puberty, were associated with mean fluorine content of the water (5.4-10.7 mg/L) and were inversely associated with mean iodine content of the water. (3) Desai et al. (1993) found a positive correlation (P < 0.001) between prevalence of goiter (9.5-37.5%) and enamel fluorosis (6.0-59.0%), but no correlation between prevalence of goiter and water iodine concentration (P > 0.05).”
In its review, however, the NRC did not have access to a series of Chinese studies that FAN has subsequently translated that provide data on the relationship between fluoride and goitre in communities with either iodine excess, or iodine deficiency. In these studies, fluoride’s capacity to increase the goitre rate has been consistently demonstrated, suggesting that the relationship between fluoride and goitre is stronger and more easily detected in populations with sub-optimal iodine intakes.
1) human Studies linking Fluoride to GOitre (Not Available to the NRC):
The following findings are from studies that the NRC did not have access to at the time of its review in 2006:
“Fluoride, a goitrogenic substance in drinking water, is another contributing factor to high GP. The fluoride concentration of drinking water was as high as 1.00 mg/kg in Chongqing municipality, which led Chongqing to have the highest GP (18.37%, 18 of 98) amongst all study areas.”
SOURCE: Meng F, et al. (2013). Assessment of iodine status in children, adults, pregnant women and lactating women in iodine-replete areas of China. PLoS One 8(11):e81294.
“Analysis of the simultaneous action of factors of the environment (iodine deficits and fluorosis) has shown that the basic cause of enlargement of the thyroid in children is an excessive intake of fluorine. Increasing the amount of iodine absorbed under conditions of excessive intake of fluorine cannot be an effective prophylactic measure directed at the elimination of iodine deficiency states.”
SOURCE: Gas’kov A, et al. (2005). The specific features of the development of iodine deficiencies in children living under environmental pollution with fluorine compounds. Gig Sanit. Nov-Dec;(6):53-5.
“In endemic areas with high fluoride and high iodine, there was greater prevalence of both fluorosis and goiter than in the areas with only one of these two factors. . . . The high fluoride/low iodine group had an increased rate of goiter as compared to low fluoride/low iodine group, possibly stemming from the toxic effects of fluoride interacting with and aggravating the damage caused by a low iodine environment.”
SOURCE: Hong F, et al. (2001). Research on the effects of fluoride on child intellectual development under different environments. Chinese Primary Health Care 15(3):56-57 (republished in Fluoride 2008; 41(2):156–60).
“In high iodine and high fluorine areas, the goiter and dental fluorosis rates of children aged from 8 to 12 were clearly higher than the control point, indicating that high iodine and high fluorosis have worse effects on children’s thyroid and teeth.”
SOURCE: Wang X, et al. (2001). Effects of high iodine and high fluorine on children’s intelligence and thyroid function. Chinese Journal of Endemiology 20(4):288-90.
“In regions where a high amount of both fluoride and iodine is present, incidents of thyroid swelling in its habitants could occur as a result, whereas this rarely occurs in regions with only a high presence of fluoride. A higher chance of one being affected by thyroid swelling is likewise more prevalent in regions containing a high amount of fluoride but low amount of iodine, and regions where a relatively lower amount of iodine is detected. We believe that in a region where the level of iodine is low, but fluoride is significantly elevated, the level of toxicity in thyroid swelling could increase.”
SOURCE: Xu Y, et al. (1994). The effect of fluorine on the level of intelligence in children.Endemic Disease Bulletin 9(2):83-84.
“For children 15 or younger, the rate of thyroid swelling was 29.8% (96/322), and the rate of dental fluorosis reached 72.98% (235/322). In the control group, the rates were 16.13% (15/93) and 18.28 (17/93), respectively, with P<0.01 in all cases, indicating that the harm caused by a high fluoride-high iodine environment is particularly serious in the case of children.”
SOURCE: Yang Y, et al. (1994). The effects of high levels of fluoride and iodine on intellectual ability and the metabolism of fluoride and iodine. Chinese Journal of Epidemiology 15(4):296-98 (republished in Fluoride 2008; 41:336-339).
“In the lower alluvial plains, endemic goiter occurred concomitantly with endemic fluorosis and the contents of iodine in both water and urine were higher, but did not reach the level found in countries where goiter could be attributed to excess intake of iodine.The fact that in the circumstances of the lower uptake of I in thyroid for 24 hours and normal values of T3, T4, TSH, endemic goiter still was slightly prevalent indicated that fluoride also was a factor responsible for goiter.”
SOURCE: Lin F, et al. (1986). A preliminary approach to the relationship of both endemic goiter and fluorosis in the valley of Manasi River, Xin-Jiang to environmental geochemistry. Chinese Journal of Endemiology 5(1):53-55.
2) HUMAN STUDIES linking f to goitre THAT WERE AVAILABLE TO NRC:
“OBJECTIVE: The study was undertaken to investigate whether endemic goitre still exists in the Northern Cape Province of South Africa more than 55 years after it was reported and, if so, whether iodine deficiency, or fluoride in the drinking water, is linked to the goitres. DESIGN: Cross-sectional study of children in three pairs of towns. SUBJECTS: The 6-, 12- and 15-year-old children (n = 671) who had been lifetime residents in two Northern Cape towns with low levels, two towns with near optimal levels and two towns with high levels of fluoride in the drinking water were recruited through the schools as study participants. RESULTS: Endemic goitre was found in all the towns except one, ranging from 5% to 29%. Iodine deficiency did not prevail in the study area because the median urinary iodine concentration, exceeding 1.58 micromol/l in all but one of the towns, indicated a more than adequate iodine consumption. The drinking water and, to a lesser extent, iodised salt were important sources of iodine. No relationship was found between fluoride in the water and the mild goitre prevalence (5% to 18%) in the four towns with either a low or near optimal fluoride content in the water. The causal factor(s) responsible for the goitres in these four towns were not clear from our data. However, the prevalence of goitre was higher (28% and 29%) in the two towns with high levels of fluoride in the water. CONCLUSION: These results indicate that either a high fluoride level in the water or another associated goitrogen, other than iodine deficiency, may have been responsible for these goitres.”
SOURCE: Jooste PL, et al. (1999). Endemic goitre in the absence of iodine deficiency in schoolchildren of the Northern Cape Province of South Africa. European Journal of Clinical Nutrition 53(1):8-12.
“We examined 22,276 individuals for presence of goitre and dental fluorosis and estimated the fluoride and iodine content of their drinking water. Overall goitre and dental fluorosis prevalences were 14.0% and 12.2%, respectively, and were significantly and positively correlated. No significant relationship was observed between water iodine level and goitre. In the study area only 0.3% of cases were visible goitre (Grade-II and above) and all goitre cases were euthyroid. This suggests that fluoride-induced goitres are brought about by anatomical or structural changes rather than functional changes.”
SOURCE: Desai VK, et al. (1993). Epidemiological study of goitre in endemic fluorosis district of Gujarat. Fluoride. 26(3):187-90.
“Areas which have endemic goitre in Kenya are highlands in the central parts of the country where there are no lakes from which iodide-rich foodstuffs, such as fish, could be found. Iodized salt has been mandatorily available in Kenya for many years. Indeed, most of the cases of goitre from these areas do not show iodide deficiency on biochemical evaluation. Many of these patients manifest clinical and laboratory findings of simple goitre (normal plasma levels of thyroxine, triiodothyronin, thyroid stimulating hormone, and normal iodine uptake values). It therefore would appear unlikely that absolute iodide deficiency per se would account for endemic goitre in Kenya. . . . It is interesting that the same areas which suffer from endemic goitre in Kenya also have the highest prevalence of fluorosis in the country. Indeed, many cases of fluorosis in Kenya have concurrent fluorosis.”
SOURCE: Obel AO. (1982). Goitre and fluorosis in Kenya. East African Medical Journal 59:363-365.
“The prevalence of goitre in 17 Himalayan villages has been estimated. Water-samples from each village were taken, and levels of iodine, fluoride, and hardness determined. In 13 villages wide variations in goitre prevalence were not attributable to differences in iodine intake, which remained constant within a narrow range. Instead, variations in goitre prevalence were found to correlate closely with the fluoride content (p=0-74; P<0-01) and with the hardness (p=0.77; P<0-01) of the water in each village. The effects of fluoride and water hardness seem to be independent.”
SOURCE: Day TK, Powell-Jackson PR. (1972). Fluoride, water hardness, and endemic goitre. Lancet 1:1135-1138.
“With regard to the slight and temporary enlargement of the thyroid encountered in the age group 14-17 (type b), detailed scrutiny of the data . . . reveals that with a fall in mean fluorine content of the water from 10.7 mg/l in Kamaguda to 5.4 mg/l in Yellareddyguda, there was a corresponding progressive fall in the incidence of pubertal goiters from 40% in Kamaguda to 9% in Yellareddyguda, However, associated with the fall in fluorine content there was also a rise in mean iodine of the water. The figures can be interpreted to indicate that, so far as type b goiters are concerned, (1) fluorine may be actually goitrogenic, and (2) high concentrations of iodine may have a goiter-preventing effect. Investigations in other areas, where the variations in fluorine content are not associated with variations in iodine content of the type encountered here, may throw light on this particular problem.”
SOURCE: Siddiqui AH. (1969). Incidence of simple goiter in areas of endemic fluorosis in Nalgonda district, Andhra Pradesh, India. Fluoride 2(2): 200-05.
In 1936 while on an investigation into poisoning of man and animal by subterranean waters in the North-Western Cape Province, one of us [D.G.S. (126-129)] encountered several cases of goitre in European women living on farms. Enquiries made, revealed that a fair percentage of people, especially women, settling in this part of the country developed enlargement of the thyroid gland within 10 to 15 years after having entered the area. This was a puzzling phenomenon as the North Western Cape Province is known to be rich in iodine. It was realized that endemic goitre in this area could not possibly be the result of primary iodine deficiency in the soil, food and water. It was thought that the cause must be sought in the drinking water. The area is semi-arid and all drinking water, except that of towns and farms situated on the Orange River, is drawn from wells and boreholes. It was also known that the subterranean waters in the North-Western Cape Province generally contain harmful quantities of fluorine. It was considered that there was a possibility that fluorine has an antithyroid (goitrogenic) action. After having consulted the literature and conducting some experiments upon rats, it was realized that fluorine is a goitrogenic agent and that endemic goitre in the North-Western Cape Province is due not to an inherent primary iodine deficiency but chiefly to the general presence of harmful quantities of fluorine in the drinking-water. It is possible that the large quantities of calcium generally present in the subterranean waters in that area, enhances the goitrogenic effect of fluorine. Generally speaking the diet of the people is very satisfactory as it included a good percentage of meat with vegetables, fruit and bread. A large percentage of the vegetables and fruit is imported.”
SOURCE: Steyn DG, et al. 1955. Endemic goitre in the Union of South Africa and some neighbouring territories. Union of South Africa. Department of Nutrition.
“The distribution of endemic goitre in the Punjab and in England is related to the geological distribution of fluorine and to the distribution of human dental fluorosis (mottled enamel). Inquiry showed the presence of dental fluorosis among school-children in two areas of Somerset where two previous observers had recorded a high incidence of goitre, and the absence of dental fluorosis in an adjoining area selected as control where endemic goitre was absent.”
SOURCE: Wilson DC. (1941). Fluorine in the aetiology of endemic goitre. The Lancet 15(6129): 212-213.
3) Animal Studies Linking Fluoride to Goiter (Not Reviewed by NRC):
“To investigate the mechanism of goiter caused by fluoride, goiter model of SD rats was produced by administering sodium fluoride in drinking water. Histological section of thyroid gland was made, and inducible nitric oxide synthase (iNOS) and vessel endothelial growth factor (VEGF) were determined by RT-PCR. Results showed that the capillary vessels in thyroid glands of the rats treated with fluoride proliferated and an obvious nodular goiter occurred in the fluoride-treated rats.Compared with the control, the contents of iNOS and VEGF in the thyroid glands of the rats with fluorosis was increased significantly (P0.05).It was concluded from the results that the mechanism of goiter caused by fluoride was that fluoride induced the over-expressions of iNOS and VEGF mRNAs in thyroid gland, which caused hyperplasia of capillary vessels.”
SOURCE: Zhang W, et al. (2008). Expressions of iNOS and VEGF mRNAs in thyroid gland of rat with goiter induced by fluoride. Chinese Veterinary Science.
“Objective: To observe the effects of fluoride on thyroid morphology, thyroid peroxidase and serum thyroid hormones. Methods: One-month ablactating SD rats were randomly divided into groups: the control group low-fluoride group, middle-fluoride group, high-fluoride group; fed with water containing different fluoride concentration by adding NaF respectively. Rats were sacrificed after being fed for six months. The morphology of thyroid was observed through light microscope. The TPO activity was measured with upgrade guaiacol method. Radio-immunoassay was used to detect serum thyroid hormones. Results: The major changes included increased follicles with colloid accumulation in high fluoride groups. With the dose of fluoride increasing, TPO activity significantly decreased as compared with the control group (P0.05). FT4 levels of the high-fluoride were significantly lower compared with the control group (P0.05). Conclusions: Chronic fluoride excess leads to definite histological changes in rat thyroid, inhibiting TPO activity so that level of thyroid hormone is decreased,which shows that fluoride can cause goiter, and cause abnormal changes of thyroid metabolism function.”
SOURCE: Cai Q, Li Hong. (2009). Effects of Fluoride on the Thyroid Morphology and Thyroid Peroxidase and Serum Thyroid Hormones. Journal of Liaoning Medical University.
“Objective: To investigate the effects of fluoride on thyroid structure in chicks. Methods: 250 one day chicks were randomly divided into 5 groups, 50 for each. Group I was the control, and other four groups, group II, III, IV, V were fed the diets containing 500, 1,000, 1,500, 2,000 mg/kg of fluorine as sodium fluoride, respectively, for 150 days. The contents of serum fluorine were determined, thyroid tissue slices were made, the weight of thyroids was weighed, and the clinical manifestations of experimental chicks were observed. Results: The animal models of chick fluorosis were successfully established. Compared with the control, the earlier changes of thyroid structure were that the relative weight of thyroid and thyroid follicle colloid in all NaF ingestion groups were less, and the size of thyroid follicles was smaller. During the later stage, the results just reversed to the earlier changes, i.e, both areas and diameters of thyroid follicle were larger and the colloid was over filled, and the follicular epithelia were obviously flatted in the enlarged follicles for being crushed by over filling colloid. Moreover, hyperplastic nodules, consisting of thyroid parafollicular cells appeared in group V. Conclusions Fluoride can seriously damage thyroid structure . During the earlier stage, fluoride can induce thyroid atrophia, however, during the later stage, it can induce thyroid enlargement which is nodular and colloid goiter.”
SOURCE: Liu GY, et al. (2001). Effects of fluoride on thyroid structure in chicks. Chinese Journal of Endemiology.
Evidence Contradicting Fluoride/Goitre Link
In 1984, Burgi and colleagues published a critique of then-existing research linking fluoride to thyroid dysfunction, including goitre. As part of this review, Burgi discusses studies that failed to find a fluoride/goitre relationship, including in some areas that had an iodine deficiency. The reference for this review is as follows:
- Burgi H, et al. (1984): Fluorine and the Thyroid Gland: A Review of the Literature. Klin Wochenschr. 1984 Jun 15;62(12):564-9.