Jennifer Anne Luke, 1997. A dissertation submitted to the School of Biological Sciences, University of Surrey. (See study or more excerpts)

Abstract:

The purpose was to discover whether fluoride (F) accumulates in the pineal gland and thereby affects pineal physiology during early development. The [F] of 11 aged human pineals and corresponding muscle were determined using the F-electrode following HMDS/acid diffusion. The mean [F] of pineal gland was significantly higher (p < 0.001) than muscle: 296 + 257 vs 0.5 + 0.4 mg/kg respectively. Secondly, a controlled longitudinal experimental study was carried out to discover whether F affects the biosynthesis of melatonin, (MT), during pubertal development using the excretion rate of urinary 6-sulphatoxymelatonin, (aMT6s), as the index of pineal MT synthesis. Urine was collected at 3-hourly intervals over 48 hours from two groups of gerbils, (Meriones unguiculatus), low-F (LF) and high-F (HF) (12 f, 12 m/group): under LD: 12 12, from prepubescence to reproductive maturity (at 9-12 weeks) to adulthood, i.e., at 7, 9, 11 1/2 and 16 weeks. The HF pups received 2.3 ug F/g BW/day from birth until 24 days where after HF and LF groups received food containing 37 and 7 mg F/kg respectively and distilled water. Urinary aMT6s levels were measured by radioimmunoassay. The HF group excreted significantly less aMT6s than the LF group until the age of sexual maturation. At 11 1/2 weeks, the circadian profile of aMT6s by the HF males was significantly diminished but, by 16 weeks, was equivalent to the LF males.

In conclusion, F inhibits pineal MT synthesis in gerbils up until the time of sexual maturation. Finally, F was associated with a significant acceleration of pubertal development in female gerbils using body weights, age of vaginal opening and accelerated development of the ventral gland. At 16 weeks, the mean testes weight of HF males was significantly less (p < 0.002) than that of the LF males. The results suggest that F is associated with low circulating levels of MT and this leads to an accelerated sexual maturation in female gerbils. The results strengthen the hypothesis that the pineal has a role in pubertal development.

EXCERPTS

Introduction:

“It is remarkable that the pineal gland has never been analysed separately for F because it has several features which suggest that it could accumulate F. It has the highest calcium concentration of any normal soft tissue in the body because it calcifies physiologically in the form of hydroxyapatite (HA). It has a high metabolic activity coupled with a very profuse blood supply: two factors favouring the deposition of F in mineralizing tissues. The fact that the pineal is outside the blood-brain barrier suggests that pineal HA could sequester F from the bloodstream if it has the same strong affinity for F as HA in the other mineralizing tissues.”

“Alongside the calcification in the developing enamel organ, calcification is also occurring in the child’s pineal. It is a normal physiological process. A complex series of enzymatic reactions within the pinealocytes converts the essential amino acid, tryptophan, to a whole family of indoles. The main pineal hormone is melatonin (MT). For some reason, young children have the highest levels of plasma MT. They also have higher plasma F levels (recommended from a dental perspective) than they did 50 years ago. An increasing number of children suffer from mild dental fluorosis: evidence that they received too much F during the first few years of life. If F accumulates in the pineal gland during early childhood, it could affect pineal indole metabolism. In much the same way that high local concentrations of F in enamel organ and bone affect the metabolism of ameloblasts and osteoblasts.”

“If F influences the high pineal MT output during early development, then the functions of the pineal may also be compromised (given that MT is the main mediator of pineal function). One putative function of the pineal is its involvement in the onset of puberty. If F compromises pineal function by altering the high rate of synthesis of MT during childhood, does this manifest as an alteration in the timing of puberty?”

Discussion:

“…the pineal gland is unique in that it can be classified as a soft or as a mineralizing tissue. In terms of mineralized tissue, the mean fluoride concentration in the pineal calcification was equivalent to that in severely fluorosed bone and more than four times higher than in corresponding bone ash, i.e., 8,900 ± 7,700 vs. 2,040 ± 1,100 mg/kg, respectively. The calcification in two of the 11 pineals analysed in this study contained extremely high levels of fluoride: 21,800 and 20,500 mg/kg.”

“The results from this study are important because the pineal gland is obviously a hitherto unrealized target for chronic fluoride-toxicity.”

Implications for children and puberty

“Fluoride is now introduced at a much earlier stage of human development than ever before and consequently alters the normal fluoride-pharmacokinetics in infants.”

“The deposition of fluoride within the child’s pineal must be a recent phenomenon…The extensive use of fluorides in dentistry has caused an unprecedented increase in plasma-fluoride levels in infants and young children.”

“If the pineal accumulates fluoride at an earlier age than in previous decades, one would anticipate that a high local concentration of fluoride within the pineal would affect the functions of the pineal, i.e., the synthesis of hormonal products, specifically melatonin. The highest levels of pineal melatonin are produced during early childhood.”

“The controlled animal study carried out in this study produce compelling evidence that fluoride inhibits pineal melatonin output during pubertal development in the gerbil.”

“Fluoride inhibited the pineal synthesis of melatonin in prepubescent male and female gerbils. The inhibitory effects of fluoride on pineal melatonin output lasted longer in males than females. A ‘normal’ pineal melatonin output was produced by the FT females at 11 1/2 weeks; by the HF males at 16 weeks.”

“The amplitude, duration and timing of pineal melatonin release, and the phase angle between melatonin rhythms and other reproductive hormones are known to be important in determining the reproductive effects of melatonin… [T]he pineals in the FT males relayed an unusual melatonin message to the tissues and organs between 11 1/2 and 16 weeks which may have affected the male reproductive system.”

Interference with enzyme activity

“Fluoride may affect the enzymatic conversion of tryptophan to melatonin. Although melatonin was the hormone investigated in this project, fluoride may also affect the synthesis of melatonin precursors, (e.g., serotonin), or other pineal products, (e.g., 5-methoxytryptamine). This would depend on the position(s) of the susceptible enzyme(s).”

“For some unknown reason, pineal calcification starts intracellularly. Calcium has been demonstrated in pinealocyte mitochondria. Therefore, it may be a mitochondrial enzyme that is sensitive to the effects of fluoride, e.g., tryptophan-5-hydroxylase. Alternatively, fluoride may affect pinealocyte enzymes which require a divalent co-enzyme because such enzymes are particularly sensitive to fluoride.”

Pineal cells may be as sensitive to fluoride as enamel cells

“The safety of the use of fluorides ultimately rests on the assumption that the developing enamel organ is most sensitive to the toxic effects of fluoride. The results from this study suggest that-the pinealocytes may be as susceptible to fluoride as the developing enamel organ. The possibility of a species difference between humans and gerbils does not allow the extrapolation of the gerbil data to humans.

“However, if increased plasma-fluoride levels cause a decline in the levels of circulating melatonin during early human development, significant physiological consequences may have already occurred. Changes in plasma melatonin concentrations are serious functional disturbances because melatonin has many functions in the organism. The pinealogists have not completely unravelled the mechanisms by which the pineal gland performs its tasks in the brain. The neurochemical phenomenon elicited by melatonin in CNS are unclear.”

Conclusion:

“In conclusion, the human pineal gland contains the highest concentration of fluoride in the body. Fluoride is associated with depressed pineal melatonin synthesis by prepubertal gerbils and an accelerated onset of sexual maturation in the female gerbil. The results strengthen the hypothesis that the pineal has a role in the timing of the onset of puberty. Whether or not fluoride interferes with pineal function in humans requires further investigation.”