A brief presentation of fluoride metabolism in humans. Sources are from Frejeskov and JJ Murray's book on fluorides.

1. FLUORIDE METABOLISM
DR. J. NESA AURLENE
II YEAR MDS
DEPARTMENT OF PUBLIC HEALTH DENTISTRY
SRM DENTAL COLLEGE, RAMAPURAM

2. CONTENTS
 Fluoride
 Ore forms of fluoride
 Sources of fluoride
Dietary sources
Non-dietary sources
 Fluoride Metabolism
 Absorption
 Distribution –
 Plasma
 Soft tissue
 Mineralised tissue
 Teeth
 Elimination
 Urine
 Breast Milk
 Feces
 Sweat

3.  Member of the halogen family
 Atomic weight 19, Atomic number 9
 Word fluorine is derived from Latin word “fluore” which means to
flow.
 At room temperature, it is a pale yellow green gas.
 Most electronegative and reactive of all elements and is rarely
found in nature in its elemental form

4.  17th most abundant element in the Earth’s crust,
ORE FORM % of fluorine
Fluorspar (CaF2) 49
Fluorapatite (Ca10F2 (PO4)6) 3.4
Cryolite 54

5. SOURCES OF FLUORIDE
 DIETARY SOURCES
 NON – DIETARY SOURCES

6. DIETARY SOURCES OF FLUORIDE
 With the exception of two foods most food substances contain very low concentrations of fluoride,
ie, below 1 ppm
( Taves 1983)
Two dietary sources that are high in fluoride content are fish and tea
Analysis of fish by Jenkins and Edgar (1973) have shown that only fish skin and bones have high
fluoride content of 8 ppm and 500 ppm respectively.
So unless these are edible (tinned sardines or tinned salmon – 1-2mg fluoride) the contribution from
fish is also negligible.

7. DIETARY SOURCES OF FLUORIDE
 Tea plants take up exceptionally high concentrations of
fluoride from the soil which eventually reaches the leaves.
 When dried, tea leaves may contain as much as 50 to 350
ppm fluoride and a tea infusion may contain 1 -3 ppm
fluoride. A heavy tea drinker may reach intakes as high as 8-
10 mg/ day (Jenkins and Edgar, 1973)

8. DIETARY SOURCES OF FLUORIDE
 Free ionic fluoride in milk is very low 0.01 ppm but milk that is ashed or treated
with acid shows a total fluoride content that is six times greater.
 Human milk has lower concentration of fluoride than cow’s milk
 Breast fed infants receive a lower fluoride intake after birth whereas bottle fed
infants with use of fluoridated water receive as much as 150 times higher
fluoride.
(Ekstrand et al 1984)

9. NON-DIETARY SOURCES OF FLUORIDE
FLUORIDE DENTIFRICES
 Fluoride compounds present in fluoride dentifrices are sodium fluoride, amine fluoride, monofluorophosphate
and stannous fluoride.
 Most toothpastes contains between 0.22% (1,000 ppm) and 0.312% (1,450 ppm) fluoride.
 High-fluoride content toothpaste generally contains 1.1% (5,000 ppm) sodium fluoride.
 A single brushing with a full ribbon of paste on a brush head provides about one gram of toothpaste and will
expose the individual to approximately 1mgF.

10. NON-DIETARY SOURCES OF FLUORIDE
The bioavailability of fluoride from sodium fluoride dentifrices is close to 100%
Small children who swallow the dentifrice can ingest .10 mg upto 2 mg.
APF gel applications require 2g to 5g of gel to be dispensed into trays which equals to about 24- 60
mg fluoride. Ingestion of APF gels can cause acute toxicity.
Ingestion of fluoride from fluoride varnishes is usually negligible.

12. ABSORPTION
 Route of fluoride absorption – Gastrointestinal tract
 When fluoride is ingested as NaF tablets taken on a fasting stomach the degree of absorption is almost 100%
 Readily soluble compounds like NaF are completely absorbed whereas compounds with lower solubility like
CaF2, MgF2, AlF3 are less completely absorbed.
 A few minutes after the dose is swallowed, there is a detectable rise in plasma fluoride concentration. Plasma
peak is reached within 30 minutes.

13. ABSORPTION
The height of plasma peak is proportional to the fluoride dose ingested and rate of absorption.
The height of plasma peak is
also dependent on the body
weight, larger the body
weight lower is the plasma
peak and vice versa.
The time for plasma peak
occurrence is 30 minutes, this
is independent of the amount
of fluoride ingested.

14. ABSORPTION
 Aqueous solutions of sodium fluoride are absorbed 100% whereas when fluoride
is taken with a glass of milk or other calcium rich breakfast the fluoride
absorption decreases to about 70% and 60% respectively.
 Likewise, when fluoride dentifrice is ingested on a fasting stomach the plasma
peak is recorded within 30 minutes.
 When dentifrice is ingested 15 minutes after a meal the peak does not occur until
after 1 hour. The peak height is also reduced.

15. MECHANISM OF ABSORPTION
 The absorptive process occurs by passive diffusion
 Fluoride is absorbed both in the stomach and small intestine
 The rate of gastric absorption is related to gastric acidity
 Fluoride is absorbed in the form of undissociated weak acid HF
 When ionic fluoride enters the acidic environment of the stomach it is converted into HF, an
uncharged molecule which readily passes through biological membranes.
 Fluoride that is not absorbed in the stomach is absorbed in the small intestine.

17. DISTRIBUTION
 Plasma is the biological fluid into which and from which fluoride must pass for its
distribution to other organs and for its elimination from the body.
 PLASMA IS OFTEN REFERRED TO AS “CENTRAL COMPARTMENT”
 In plasma, fluoride exists as ionic and non-ionic fluoride which is together called
total plasma fluoride. Ionic form has biological significance, it is not bound to
plasma proteins.
 Normal fluoride concentration of plasma ranges between 0.7-2.4µM

18. DISTRIBUTION
Plasma fluoride concentrations are not
homeostatically regulated but instead they rise
and fall according to the pattern of fluoride intake.
Chronic fluoride intake, recent intake, relative rates
of bone accretion and dissolution, renal clearance
of fluoride all have an effect on plasma fluoride
concentration.

20.  When plasma fluoride concentration is plotted as a function of time there are
three phases
a) An Initial increase
b) Rapid fall for about 1 hour
c) Slower decline
These three phases represent absorption, distribution and elimination respectively.

21.  In the declining portion of the curve the α-phase is known as the distribution
phase and the ꞵ phase is the elimination phase.
 During alpha phase fluoride is rapidly distributed to well perfused tissues such as heart,
kidneys, liver and bone.
 Fluoride is slowly distributed to poorly perfused tissues such as resting skeletal muscle
and adipose tissue.
Beta phase represents elimination of fluoride, plasma half life for fluoride in human adults is
3.38 hours and is the time required for fluoride concentration to fall by one-half.

22. DISTRIBUTION IN SOFT TISSUES
 Fluoride is distributed from plasma to all tissues and organs.
 Steady state tissue to plasma fluoride concentration falls between 0.4 and 0.9
 Exceptions to this range include kidney, brain and adipose tissue
 Fluoride is concentrated in high levels in the kidneys, the organ as a whole has higher F concentration than
plasma
 Blood brain barrier effectively prevents passage of fluoride into CNS
 F concentration in brain and fat is only 20% to that of plasma
 Except in case of ectopic mineralization that occurs in large arteries and placenta near term the soft tissues do
not accumulate fluoride.

23. DISTRIBUTION TO MINERALIZED TISSUES
 Fluoride is a mineralized tissue seeker and the clearance rate by bone is higher than that of calcium.
 99% of F in human body is found in the mineralized tissues
 Selective affinity of F to mineralized tissues is due to,
Short term – uptake on the surface of bone crystallites by isoionic and heteroionic exchange
Long term – F incorporated in the crystal lattice structure in the form of fluorapatite or fluorhydroxyapatite

24. DISTRIBUTION TO MINERALIZED TISSUES
 During growth phase a high portion of ingested F will be deposited in the skeleton.
 The balance of fluoride in the body can be positive or negative.
 When fluoride intake is less in infants or when fluoride is derived from biological sources with less F content
urinary excretion exceeds intake – negative balance.
 Under normal conditions approximately one half of the daily intake of F by adults will be deposited in the
bone and then excreted in the urine.

25. DISTRIBUTION TO MINERALIZED TISSUES
 Highest F concentration in areas of active growth, endosteal and periosteal surfaces, lower in central
compact bone.
 Reversibly bound to bone – reduced intake leads to increased excretion of F
 Individuals who move from a high fluoride area to low fluoride area show high concentrations of fluoride in
urine for prolonged periods of time.
 Fluoride is mobilized continuously and slowly from the bone.

26. DISTRIBUTION - TEETH
 Amount of fluoride in the outer enamel ranges from 2,200 ppm to 3,200 ppm
 Accumulation is largely restricted to outer surface enamel
 Acquisition of fluoride directly depends upon porosity of enamel
 Penetration of fluoride into fully mineralized enamel is very slow because the porosity
is as low as 0.1% in fully mineralized enamel.
 Dentin F – 200-300 ppm. Has smaller apatite crystals and hence a larger surface area
which increases its capacity for uptake of F.
 Higher concentrations closer to the pulp than in outer layers.
 Cementum – 4500 ppm. Fluoride concentration decreases from surface to interior

27. EXCRETION
 MECHANISM – Glomerular filtration and limited potential for reabsorption from
kidney tubules.
 Renal clearance of fluoride in healthy young and middle aged adults is
approximately 35ml/minute ( range 30-50 ml/minute)
 In children who consume drinking water containing fluoride of 1mg/litre or take a
tablet 1mg fluoride everyday, the excretion varies significantly between 25 and 35
μg F-/hour.
 Children with low fluoride intake in the age group of 9-14 years tends to excrete
approximately 10 μg F-/hour.

28. EXCRETION
 The percentage of filtered fluoride reabsorbed from renal tubules can range from
about 10% to 90%.
 The degree of reabsorption depends on urinary pH.
 Thus in acidic conditions undissociated acid HF is formed which readily diffuses
out of the tubules.
 In alkaline conditions, fluoride ion predominates and as it is relatively
impermeable and remains within the tubules to be excreted.

29. BREAST MILK
 The concentration of fluoride in breast milk is about 0.4µM
 Studies of lactating mothers have shown that there is a limited transfer of fluoride
from plasma to breast milk.
(Ekstrand J)

30. FECES
 Excretion of fluorides via feces is of less quantitative importance. Fluoride in feces
is the fluoride that remains unabsorbed.
 Fecal fluoride usually accounts for less than 10% of amount ingested everyday.

31. SWEAT
 In temperate climates, excretion by sweating is negligible.
 In tropical climates, where fluid loss from the body is as much as 4-6 L/day, the
excretion of fluoride will be about one tenth of a milligram.

32. References
 Ekstrand J, Fejerskov O, Silverstone LM, editors. Fluoride in dentistry. Copenhagen:
Munksgaard; 1988.
 Murray JJ. Fluorides in caries prevention. John Wright & Sons Ltd.; 1976.
 Ekstrand J, Boreus LO, De Chateau P. No evidence of transfer of fluoride from
plasma to breast milk. British medical journal (Clinical research ed.). 1981 Sep
19;283(6294):761.
 Ekstrand J. Relationship between fluoride in the drinking water and the plasma
fluoride concentration in man. Caries research. 1978;12(3):123-7.
 Ekstrand J, Spak CJ, Vogel G. Pharmacokinetics of fluoride in man and its clinical
relevance. Journal of dental research. 1990 Feb;69(2_suppl):550-5.

33. References
 Ekstrand J, Ziegler EE, Nelson SE, Fomon SJ. Absorption and retention of dietary
and supplemental fluoride by infants. Advances in dental research. 1994
Jul;8(2):175-80.
 Whitford GM. Fluoride distribution between plasma and blood cells. InZahn Mund
und Kieferheilkunde 1981 Dec 1.
 Shen YW, Taves DR. Fluoride concentrations in the human placenta and maternal
and cord blood. American journal of obstetrics and gynecology. 1974 May
15;119(2):205-7.
 Parkins FM, Tinanoff N, Moutinho M, Anstey MB, Waziri MH. Relationships of
human plasma fluoride and bone fluoride to age. Calcified tissue research. 1974
Dec 1;16(1):335-8.