6. Fluoride

6.1. Main functions

Fluoride is the world’s 13th most abundant element [151], being widely distributed in the environment, occurring in soils, rocks, and water: it is therefore naturally present in the food and drink we but its status as “essential” is debated.

It is well absorbed by the small intestine. and gets attached to bone and teeth, transforming apatite into fluoroapatite. Nearly 99% of the body’s fluoride is bound strongly to calcified tissues. Fluoride in bone appears to exist in both rapidly and slowly exchangeable pools [152,153]. Blood and bone concentration are in equilibrium [154]. About half the absorbed fluoride is excreted via the kidneys. Fluoride skeletal uptake is also modified by factors such as the activity of bone remodeling and age.

Fluoride inhibits glycolysis enzymes, a capacity which is used in laboratories to assist blood glucose determination [155]. Main sources include foods, fluoridated water, fluoridated toothpastes and some dietary supplements [156]. Fluoride intake from most foods is low, but tea may be an important source of high doses as shown in a well documented intoxication case report [157]. Fluoride’s unique role in mineralization is the reason for its recognition as a beneficial trace element for dental health of humans [158].

6.1.1. Needs

There is no DRI. Adults typically consume <0.5 mg of fluoride daily in food [157]. Nutritional intakes in adults are safe up to 4 mg/day in men and 3 mg/day in women.

Fluoridation programs were started in numerous western countries in the 1960s [151]. The fluoridation of drinking water aims to bring fluoride levels up to a range preventing or minimizing tooth decay by 26-44% in children, teenagers and adults [153]. Some bottled drinking waters contain up to 8 mg/l. The need for fluoridation remains debated [159].

Fluoride can reasonably be provided in EN at doses of up to about 3 mg/day.

For PN, the need for adding fluoride is debated, especially in USA [160]. However, fluoride has been supplied for over 40 years as part of standard multi-element mixtures in European products at a dose of 0.95 mg without any side effects, and with the potential for beneficial effects on bones and teeth. This dose continues to be recommended for standard PN.

6.2. Biomarkers and analytical methods

Fluoride may be determined in serum, or in 24hr urine collection. Analytical methods use a fluoride-specific electrode (urine), flow injection analysis coupled with a fluoride-specific electrode (serum and urine) (FIA-FE) [161], or by ion chromatography with conductivity detection (IC-CD).

6.2.1. Reference values

Serum <50mg/l (or <2500 nmol/l), and for urine <0,5 mg/24 h or < 25 nmol/24 h. When used in treatment of osteoporosis, the serum values are increased 5e10 times.’

In professional or other (hydro-telluric) exposure, the urinary toxicity range is 10 mg/24 hr.

Dental fluorosis is diagnosed by bilateral symmetrical developmental enamel opacities (brown discoloration) [162].

6.2.2. Unit conversion

From mg/l multiply by 52.6 nmol/l; from SI nmol/l multiply by 0.019 mg/l

6.2.3. Effect of inflammation

No human data available. In rats, fluoride seems to induce IL-17 mediated inflammation in cardiac tissues [163].

6.3. Deficiency

Reported unequivocal signs of fluoride deficiency are almost non-existent. Pharmacological doses prevent caries.

6.3.1. When and how to treat?

Fluoride is principally a public health issue. Both inadequate and excessive fluoride intakes can affect dental health [151]. Inadequate intakes are associated with increased tooth decay (dental caries) and excessive intakes with damage to tooth enamel (dental fluorosis).

6.4. Toxicity

Chronic toxicity is most frequent, and may present as gastric complaints, anemia, osteomalacia, teeth problems, and neuromuscular and gastrointestinal symptoms. Chronic renal failure has been described. Chronic toxicity has been observed along with excessive water supplies and industrial exposures (excess of 2 mg/day) resulting in dental fluorosis and mottled enamel. Skeletal fluorosis is a rare toxic osteopathy characterized by massive bone fluoride fixation that occurs with doses 10-25 mg/day for many years. The disease is an endemic problem in some parts of the world and results from prolonged ingestion or rarely by industrial inhalation of high amounts of fluoride [164].

In patients on home PN for chronic intestinal failure (short bowel), high blood fluoride values have been observed in a series of 31 patients who developed osteoporosis and were explained by high fluoride intakes from drinking water [165].

An increased prevalence of cardiac complications has been observed in residents of fluorosis endemic areas chronically exposed to fluoride [163].

Fluoride might also have an impact on children’s neurological development as shown by a meta-analysis. Greater exposure to high levels of fluoride in water was significantly associated with reduced levels of intelligence in children [166]. Some authors consider that artificial water fluoridation should be reconsidered globally [151] and studies are ongoing [167].

Poisoning most commonly follows ingestion (accidental or intentional) of fluoride-containing (mostly dental) products. In many parts of the world (e.g., regions of India and China), elevated levels of fluoride in groundwater result in chronic fluoride toxicity (fluorosis). The clinical course of systemic toxicity from ingested fluoride begins with gastric signs and symptoms and can develop with alarming rapidity. Toxicity treatment includes minimizing absorption by administering a solution containing calcium, monitoring and managing plasma calcium and potassium concentrations, acid-base status, and supporting vital functions [154].

There is no established treatment for skeletal fluorosis [157]. Calcium and vitamin D supplementation might mineralize or prevent excessive osteoid production. Oral calcium can diminish bone resorption, perhaps by reducing parathyroid hormone secretion, but may not block gut absorption of fluoride.

6.5. Recommendations No 7 – fluoride

6.5.1. When to measure?

Recommendation 7.1
In case of suspicion of fluorosis blood determination should be performed.
Grade of recommendation GPP – Consensus 88%

6.5.2. What to measure?

Recommendation 7.2

The fluoride status shall be determined by blood measurements.
Grade of recommendation A – Strong consensus 91%

6.5.3. How much to provide in typical enteral or parenteral nutrition regimens?

Recommendation 7.3

Enteral nutrition may provide up to 3 mg fluoride per day with 1500 kcal.
Grade of recommendation 0 – Strong consensus 100%

Comment
Fluoride is not essential in children nor in adults. Small doses of fluoride (0-3 mg per day) may be beneficial [25].

Recommendation 7.4

There is no equivalent recommendation for parenteral nutrition.

Grade of recommendation GPP – Strong consensus 100%

Comment
Although not essential in adult PN, 0.95 mg per day has been provided without any complication and may be continued.

6.5.4. When to treat?

Recommendation 7.5
In case of fluoride poisoning, symptomatic treatment should be applied.
Grade of recommendation GPP – Strong consensus 91%

6.5.5. How to treat?

Recommendation 7.6

In case of acute poisoning, support of vital function and electrolyte management should be applied.
Grade of recommendation GPP – Strong consensus 97%

Recommendation 7.7

There is not a specific treatment that can be offered to treat skeletal fluorosis, except to control the source of the excess of fluoride exposure.
Grade of recommendation GPP Strong consensus 94%

See:
Table 15
ESPEN Recommendations for daily trace element and vitamin intakes – 2022 (all values are per day).

References cited

[151] Peckham S, Awofeso N. Water fluoridation: a critical review of the physiological effects of ingested fluoride as a public health intervention. Sci World J 2014;2014:293019.

[152] Bergmann KE, Bergmann RL. Salt fluoridation and general health. Adv Dent Res 1995;9:138-43.

[153] Spencer AJ, Do LG, Mueller U, Baines J, Foley M, Peres MA. Understanding optimum fluoride intake from population-level evidence. Adv Dent Res 2018;29:144-56.

[154] Mart?nez-Mier E. Fluoride: its metabolism, toxicity, and role in dental Health. J Evid Based Comple Alter Med 2012;17(1):28-32.

[155] Gupta S, Kaur H. Inhibition of glycolysis for glucose estimation in plasma: recent guidelines and their implications. Indian J Clin Biochem 2014;29:262-4.

[156] Kanduti D, Sterbenk P, Artnik B. Fluoride: a review of use and effects on health. Mater Sociomed 2016;28:133-7.

[157] Whyte MP, Essmyer K, Gannon FH, Reinus WR. Skeletal fluorosis and instant tea. Am J Med 2005;118:78-82.

[158] Cerklewski F. Fluoride bioavailability and nutritional and clinical aspects. Nutr Res 1997;17:907-29.

[159] Aoun A, Darwiche F. Al hayek S, doumit J. The fluoride debate: the pros and cons of fluoridation. Prev Nutr Food Sci 2018;23:171-80.

[160] Nielsen FH. Micronutrients in parenteral nutrition: boron, silicon, and fluoride. Gastroenterology 2009;137:S55-60.

[161] Itai K, Tsunoda H. Highly sensitive and rapid method for determination of fluoride ion concentrations in serum and urine using flow injection analysis with a fluoride ion-selective electrode. Clin Chim Acta 2001;308:163-71.

[162] Cutress TW, Suckling GW. Differential diagnosis of dental fluorosis. J Dent Res 1990:69. Spec No:714-20; discussion 21.

[163] Quadri JA, Sarwar S, Pinky Kar P, Singh S, Mallick SR, Arava S, et al. Fluoride induced tissue hypercalcemia, IL-17 mediated inflammation and apoptosis lead to cardiomyopathy: ultrastructural and biochemical findings. Toxicology 2018;406-407:44e57.

[164] Sellami M, Riahi H, Maatallah K, Ferjani H, Bouaziz MC, Ladeb MF. Skeletal fluorosis: don’t miss the diagnosis! Skeletal Radiol 2020;49:345-57.

[165] Bouletreau PH, Bost M, Fontanges E, Lauverjat M, Gutknecht C, Ecochard R, et al. Fluoride exposure and bone status in patients with chronic intestinal failure who are receiving home parenteral nutrition. Am J Clin Nutr  2006;83: 1429-37.

[166] Duan Q, Jiao J, Chen X, Wang X. Association between water fluoride and the level of children’s intelligence: a dose-response meta-analysis. Publ Health 2018;154:87-97.

[167] James P, Harding M, Beecher T, Parnell C, Browne D, Tuohy M, et al. Fluoride and caring for children’s teeth (FACCT): clinical fieldwork protocol. HRB Open Res 2018;1:4.

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