FLUORIDE A DOUBLE EDGED SWORD

Prévia do material em texto

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FLUORIDE: A DOUBLE EDGED SWORD 
 
Shweta Sachan*, Aditi Singh#, Jyoti Prakash
1
, Garima Awasthi
1 
 
*Research scholar, #Assistant Professor, 
1 
Senior lecturer, Amity Institute of Biotechnology, 
Amity University, Lucknow. 
 
ABSTRACT 
Fluorine is a highly reactive gas seldom occurs in nature in elemental 
form. It combine with other elements or molecules and form fluorides 
(F-), e.g. Calcium fluorite (CaF2), Cryolite (Na3AlF6) etc with a very 
high affinity. Geological crust in India is very rich in fluoride bearing 
minerals. Groundwater with high fluoride concentration occur in many 
areas of the world including large parts of China, Africa, Southern 
Asia and the middle East, including India. Although drinking water is 
usually the largest contributor to the daily fluoride intake, it is also 
found in atmosphere originating from the dusts of fluoride containing 
soils, from gaseous industrial wastes and from burning of coal fires in 
populated areas. Fluoride can reduce or prevent dental decay and strengthen bones, so that it 
prevents bone fractures in older people. When the level of fluoride is naturally low, studies 
have shown higher levels of dental caries (tooth decay) and fractures. But is too much of a 
good thing always beneficial? Excessive ingestion of fluoride during the early childhood 
years can damage the tooth-forming cells, leading to a defect in enamel known as dental 
fluorosis. Another well known cause of excess fluoride is skeletal fluorosis, which is difficult 
to diagnose in early stages and can be confused with various forms of arthritis. Apart from 
teeth and bone, excess fluoride has been found to be affecting kidney, brain, thyroid gland 
and the gastrointestinal gland. Fluoride is purposely added to toothpastes and sometimes 
other products to promote dental health. Fluoride is also found in some food stuffs and in the 
air, so the amount of fluoride people actually ingest may be higher than assumed. 
 
KEY WORDS: Fluoride, fluorosis, dental caries, skeletal fluorosis. 
 
 
 
World Journal of Pharmaceutical Research 
 SJIF Impact Factor 5.045 
Volume 3, Issue 7, 241-254. Review Article ISSN 2277 – 7105
 
Article Received on 
10 July 2014, 
 
Revised on 04 August 2014, 
Accepted on 29 August 2014 
*Correspondence for 
Author 
Shweta Sachan 
Research scholar, Amity 
Institute of Biotechnology, 
Amity University, Lucknow. 
 
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INTRODUCTION 
Fluorine is the 13th most abundant element that does not occur in free state in nature because 
of its high reactivity and thus have strong affinity to combine with other minerals to form 
compounds known as fluorides, fluorspar, cryolite and fluorapatite (Ando et al, 1998). 
Inorganic fluorine compounds are commonly used in industries. They are used in aluminium 
production and as a flux in the steel and glass fibre industries. They can also be released to 
the environment during the production of phosphate fertilizers (which contain an average of 
3.8% fluorine), bricks, tiles and ceramics. Fluorosilicic acid, sodium hexafluorosilicate and 
sodium fluoride are used in municipal water fluoridation schemes. Generally the surface 
water does not contain high fluoride but ground water is usually contaminated with high 
fluoride because of its leaching in to water percolating through fluoride rich rocks (Gavriliuk 
et al, 2007). Groundwater with high fluoride concentration occurs in many areas of the world 
including large parts of China, Africa, Southern Asia and the Middle East fluorosis has 
increased in Ireland, Canada, US, and other part of the world (Warren & Levy, 2003; Browne 
et al, 2005). Fluoride is usually very easily found naturally in low concentration in drinking 
water and foods. Human beings are exposed to fluoride by many different sources (Ando et 
al, 1998). 
 
 
Sources of fluoride 
 
1.1 Fluoride in drinking water 
Major source of fluoride is drinking water and since it is the most assimilable form of 
fluoride, it is the most toxic. There is no fluoride in soft water while in hard water the 
concentration of fluoride may be as high as 10 ppm. When water is fluoridated, it is adjusted 
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to between 0.7 and 1.2 milligrams (mg) of fluoride per liter. This concentration has been 
found to decrease the incidence of dental caries while minimizing the risk of dental fluorosis 
and other adverse effects. It is estimated that around 200 million people are under the 
dreadful fate of fluorosis. China and India are the two most populous countries of the world, 
are the worst affected. Nearly 12 million of the 85 million tons of fluoride deposits on the 
earth’s crust are found in India (WHO, 1994). It is not surprising that the fluorosis is endemic 
in 17 states of India (Suthar et al, 2008) with Andhra Pradesh, Haryana, Punjab, Gujarat, 
Rajasthan, Tamil Nadu and Uttar Pradesh being most severally affected (Meenakshi & 
Maheshwari, 2006). Even the bottled mineral water may be a source of excessive fluoride 
ingestion (Villena et al, 1996), therefore a sanitary regulatory system for the control of level 
of fluoride in bottled mineral water is necessary. Fluoride has been added to drinking water 
for almost fifty years and the studies have validated the cavity lowering effects of fluoride 
supplementation and failed to show any increase in diseases due to this public health 
measure. Fluoride supplementation ranks along with water purification and vaccines as one 
of the top public health measures of the 20th century. 
 
1.2 Food and beverages sources 
The fluoride content of foods may vary from place to place depending upon its content in soil 
and water. In a previous study (Lakdawala & Punekar, 1973) it is find out that the fluoride 
content in food and agricultural products, wheat (3.27 - 14.03 ppm), Bengal gram (3.84 - 4.84 
ppm) and many vegetables like Amaranthus, cucumber, potato and onion have been found to 
have significantly high levels of fluoride. Another very rich source of fluoride is tea, which 
concentrates fluoride in its leaves (dry leaves having 39.8 – 68.59 ppm). The tree plant has 
fluoride concentration ranging from 3.2 to 400 mg/kg, while its infusion contains up to 8.6 
mg/l, depending upon the infusion time, amount and variety of tea (Field et al, 1976). Even 
in juices, fluoride level is very high, which may range from 0.14 to 6.8 (Stannard et al, 1991). 
The fluoride content of foods from animal sources has also been found to be high, e.g. 
mutton: 3 to 3.5 ppm, beef: 4.0 to 5.0 ppm and pork: 3.0 to 4.5 ppm etc. (Field et al, 1976). 
Marine fish that are consumed with their bones (e.g. Sardines), foods made with 
mechanically separated (boned) chicken, such as hot dogs, canned meats, and infant foods 
add fluoride to the diet (Stannard et al, 1991). 
 
 
 
 
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Table 1: Some representative food item and their fluoride content (Field et al, 1976; 
Stannard et al, 1991). 
Food Serving Fluoride (mg) 
Tea 100 ml 0.1-0.6 
Grape juice 100 ml 0.02-0.28 
Canned Sardines (with bones) 100 gm 0.2-0.4 
Fish (without bones) 100 gm 0.01-0.17 
Chicken 100 gm 0.06-0.10 
 
1.3 Fluoride supplements 
Fluoride supplements are intended for children living in areas with low water fluoride 
concentrations for the purpose of bringing their intake to approximately 1 mg/day. Fluoride 
content in raw materials like Calcium carbonate, talc and chalk, used for manufacturing of 
paste can be as high as 800 - 1000 ppm (Levy & Zarei, 1991; Rock & Sabieha, 1997), which 
rises up to 1000 - 4000 ppm in fluoridated brands. Some drugs if taken for a longer time, may 
cause chronic adverse effects of fluoride e.g. Sodium Fluoride for the treatment of 
osteoporosis or use of fluoride mouth rinse (RGNDWM, 1993). 
 
1.4 Other sources of fluoride 
Inorganic fluoride compounds are used in production of aluminium and phosphate fertilisers 
(RGNDWM, 1993), which may lead to occupational exposure. 
 
2.Fluoride In Human Development 
Fluoride is not considered to be essential for human growth and development, but it is 
beneficial in the prevention of dental caries. So, intentional fluoridation of drinking water 
and the development of fluoride containing oral care products, foods and supplements 
(fluoride tablets) have been employed since the early 20th century in several parts of the 
world as a public health protective measure against tooth decay (SCHER, 2011). Ingested 
fluoride is rapidly absorbed through gastrointestinal tract and lungs (Gupta et al, 1993). The 
peaks are reached after 30 min inter in blood. The rapid excretion takes place through renal 
system over a period of 4 to 6 hour (Rolla, 1988). In children less than three years of age, 
only about 50% of the total absorbed amount is excreted but in adults and children over 3 
years about 90% is excreted. The biological half life of bound fluoride is several years 
(Cerklewski, 1997). Fluoride is the most important trace element affecting bones and teeth. 
Approximately 90% of fluoride retained in the body is deposited in skeleton and teeth. In fact 
fluoride is the only element known to stimulate bone growth. It along with large quantities of 
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calcium is a large part of what makes our bones strong. Bones start to lose calcium when the 
body does not receive enough fluoride and then become weak and brittle. 
 
Table 2: The Average Fluoride Intake for different age groups (ADA, 2005) 
Adequate Intake (AI) for Fluoride 
Life Stage Age Males (mg/day) Females (mg/day) 
Infants 0-6 months 0.01 0.01 
Children 1-3 years 0.7 0.7 
Children 9-13 years 2.0 2.0 
Adults 19 years and older 4.0 3.0 
Pregnancy All ages - 3.0 
Breastfeeding All ages - 3.0 
 
Fluoride is required in small amounts only for good health. A small amount of 1 ppm is 
considered enough for normal healthy teeth (Waterfront, 1999). When the fluorine content is 
high, fluorosis ensues. The average adult man may ingest about one milligram of fluorine 
daily from drinking water that contains one part per million (1 ppm). The average diet may 
provide 0.25-0.35 mg of fluorine (ATSDR, 2003). 
 
3.Benefits of Fluoride 
If fluoride provide in limited amount it is very beneficial to us. 
 
3.1 Dental caries 
Specific carcinogenic (cavity-causing) bacteria found in dental plaque are capable of 
metabolizing certain carbohydrates (sugars) and converting them to organic acids that can 
dissolve susceptible tooth enamel. If it not checked on time, the bacteria may penetrate 
deeper layers of the tooth and progress into the soft pulp tissue at the centre. Untreated caries 
can lead to severe pain, tooth loss or extraction, local infection, nutritional problems and 
serious systemic infections in susceptible individuals. Increased fluoride exposure, most 
commonly through fluoridation of water has been found to decrease dental caries in children 
and adults (CDC, 2001). Some studies suggest that fluoride’s caries preventive benefit is best 
achieved when a person receives both topical and pre-eruptively administered systemic 
fluoride (Singh et al, 2004; 2007; Groeneveld, 1999), the preventive benefit derived from 
systemic fluoride intake specifically in the first six months of life has not been established. 
 
3.2 Fluoride in the prevention of Osteoporosis 
Osteoporosis defined as low bone mass and increased susceptibility to fracture is a reflection 
of the sum of peak bone mass and any bone that has been lost once peak mass has been 
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attained. Experimental and clinical data has shown that fluoride stimulate bone formation 
directly and increase bone mass in patients who already have osteoporosis (Kleerekoper, 
1998). Several bone formation, stimulation therapies are in developing stage. Fluoride as a 
naturally occurring element is difficult to patent, so this has kept major pharmaceutical 
companies from investing heavily in fluoride therapy despite its obvious potential. So 
pharmacologic and pharmacokinetics studies of fluoride are limited in scope (Kleerekoper, 
1998). 
 
 4. Adverse Effect of Fluoride 
Although helpful for dental health in low dosage but chronic exposure to fluoride interferes 
with bone formation when it is in large amounts. The ill effects of fluoride depend on 
concentration of fluoride in drinking water and food etc, low concentration and high 
alkalinity of water, age, donation of intake, pregnancy and lactation (WHO, 1970). The 
fluoride intoxication can be acute or chronic. In acute intoxication alimentary cardio vascular, 
respiratory & central nervous systems are affected with fatal outcome some times (WHO, 
1984). The toxic effects of long term ingestion of fluoride (chronic intoxication) can be 
dental and skeletal fluorosis or non skeletal manifestation. 
 
4.1 Dental fluorosis 
Excessive ingestion of fluoride during the early childhood years can damage the tooth 
forming cells, leading to a defect in enamel known as dental fluorosis (Gosselin et al, 1984). 
Dental fluorosis is a developmental disturbance of dental enamel caused by excessive 
exposure to high concentrations of fluoride during tooth development. The permanent teeth 
are generally expected, though it affects primary teeth (Teotia, 1999). The risk of fluoride 
over exposure occurs between the ages of 3 months and 8 years (IPCS, 2002). Fluoride in its 
mild forms (which is the most common) appears as unnoticeable as tiny white streaks in the 
enamel of the tooth. When it is in its most severe form, tooth appearance is marred by brown 
markings or discoloration. The enamel may be pitted, rough and hard to clean. The stains and 
spots left by fluorosis are permanent and may darken over time (Dean & Elvove, 1935). 
Clinical dental fluorosis is an irreversible disease (Gavriliuk et al, 2007) and morbidity due to 
this can be as high as 35 – 69 % (Choubsia et al, 2007; Gopalkrishnan et al, 1999). In a recent 
study done to see effects of high ground water fluoride in endemic high fluoride areas, dental 
and skeletal fluorosis was found to be significantly prevalent(Srivastava et al, 2011) with 
28.64 % and 14.11 % incidence respectively. 
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A case of dental fluorosis in a white adult male 
 
4.2 Skeletal fluorosis 
Another well known cause of excess fluoride is skeletal fluorosis, which is difficult to 
diagnose in early stages and can be confused with various forms of arthritis. Joint pain and 
stiffness are well known symptoms of excessive fluoride intake. In the early clinical stage of 
skeletal fluorosis, symptoms include sensations of burning, pain in the bones and joints, 
pricking, muscle weakness and tingling in limbs, chronic fatigue and restricted joint 
movements. During this phase changes in the pelvis and spinal column can be detected on x-
rays (Hileman, 1988). In the second clinical stage, pain in the bones become constant and 
inter osseous membrane, some of the ligaments and tendon begin to calcify. Osteoporosis can 
occur in the long bones and early symptoms of osteosclerosis may be present (Mithal, 1993). 
Bony spurs may also appear on the elbow, limb bones, especially around the knee and on the 
surface of tibia and ulna with muscular wasting and premature aging in extreme cases (Wang 
et al, 1994). According to one study, hip and wrist fractures increase as fluoride in increased 
from 1 mg/l to 4 mg/l Suggesting fluoride exposure effects (NRC, 2006). 
 
A severe case of skeletal fluorosis in a adult male (abuzeid & Elhataw, 2006) 
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4.3 Non Skeletal Fluorosis 
4.3.1 Adverse Effects on the kidney 
Chronic ingestion in excess of 12 mg/day is expected to cause adverse effects like urine 
reduction and itching in region of axilla (NRC, 2006). Those with impaired kidney function 
are more susceptible to adverse effects. 
 
4.3.2 Effects on Nervous System 
In persons with fluoride toxicity nervousness and depression, tingling in fingers, polydipsia 
(excessive thirst) and polyuria (frequent urination) suggest adverse effects on brain 
(RGNDWN, 1993). Four epidemiological studies have noted a correlation between increased 
fluoride and low IQ (Tang et al, 2008). The most rigorous of these compared an area with 
mean water concentration of 0.36 ± 0.15 mg/L (range 0.18–0.76 mg/L) to an area with 2.47 ± 
0.79 mg/L (range 0.57–4.50 mg/L). The NRC speculates that effects on the thyroid could lead 
to poor test results (Liu & Qian, 2008). Two Chinese meta-analyses which included the 
previously mentioned studies have also noted this correlation. 
 
 4.4 Thyroid 
Fluoride has inhibitory effect on iodine uptake (Yang et al, 1994) and suppressive effect on 
the thyroid is more severe when iodine is deficient (Strunecká et al, 2002). Thyroid effects in 
humans were associated with fluoride levels, when iodine intake was adequate fluoride level 
was the 0.05–0.13 mg/kg/day and when iodine intake was inadequate fluoride level was 
0.01–0.03 mg/kg/day (NRC, 2006). Its mechanisms and effects on the endocrine system 
remain still unclear. 
 
4.5 Effects on Gastrointestinal (GI) System 
The complaint of GI system like acute abdominal pain, diarrhea, constipation, tenderness, 
nausea etc. are taken as early warning signs of fluoride toxicity (Gupta et al, 1992). Fluoride 
with hydrochloric acid forms hydrofluoric acid, which is highly corrosive and destroys 
stomach and intestinal mucosa (Siddiqui, 1970). 
 
4.6 Diabetes and Fluoride 
Trivedi et al. (1993) had shown that fluoride toxicity in humans could result in significant 
abnormalities in glucose tolerance, which are reversible upon removal of excess fluoride. 
 
 
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5. Role of Diet in Fluorosis 
The diet plays a very important double action role because high fluoride in diet increases the 
toxic effects of fluorosis, whereas diet rich in calcium and vitamin C helps in overcoming this 
toxicity (WHO, 1984). The fluoride is present in either organic bound form or inorganic 
form, toxicity of the bound form of fluoride is much less than the other. On an average 
fluoride intake from food may range from 2 to 8.0 mg/day depending on the type of food 
consumed (Boyd & Cerklewski, 1987). Studies have shown that food fluoride plays a role in 
dental fluorosis in area with low fluoride in drinking water and in skeletal and clinical 
fluorosis where drinking water fluoride is playing major role (Rao, 1984; 1990). 
 
6.Treatment And Prevention 
There is no specific anti floristic drug available but recent studies (Gupta, 1993; 1994) have 
indicated that fluorosis can be reversed in children by a cheap and easily available therapeutic 
regimen of calcium, Vitamin C and vitamin D. Since the people living in fluoride rich area 
have no choice except to drink the available fluoride contaminated water, the first and 
foremost measure is to defluoridate water & bring it to WHO standards. Also It has been 
shown that cessation of water fluoridation has caused significant reduction of dental fluorosis 
(Clark et al, 2006). Various commonly used domestic defluoridation processes are available 
for fluoride contaminated drinking water like Nalgonda process (Nawlakhe et al, 1975), 
Activated alumina process (Rubel & Woosely, 1979; Venkobachar & Iyengar, 1996), Krass 
process (Gupta, 1997; Agarwal et al, 1999) etc. Also restricting fluoride rich food, cosmetics 
and increasing use of calcium, vitamin C and protein rich food also help in abrogating 
adverse effects of fluoride. Apart from that creating disease awareness in rural and urban 
population is also very important. 
 
7.CONCLUSION 
Fluorine is an easily available element and present in human body from sources like food, air, 
soil, supplements and drinking water. In limited amount fluoride is good for us. But too much 
of a good thing is not always very beneficial. It can prevent or reduce dental decay and 
strengthen bones, it prevents bone fractures in older people but in excess amount it is cause of 
dental fluorosis, skeletal fluorosis, affects kidneys, brain, thyroid glands and the 
gastrointestinal gland. Fluoride is purposely added to toothpastes, mouthwash and sometimes 
other products to promote dental health (Pizzo et al, 2007; DePola, 1997). It should be noted 
that fluoride is also found in some food stuffs and in the air, so the amount of fluoride people 
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actually ingest may be higher than assumed and this higher amount may become very 
harmful for us. So the use of fluoride in toothpastes and other stuffs should be carefully 
assesses with exhaustive in different parts of India to identify area with high water fluoride 
content. 
 
8.ACKNOWLEDGEMENT 
Authors are thankful to Mr. Aseem Chauhan, Chancellor Amity University Rajasthan & 
Haryana and Chairman Amity University Uttar Pradesh Lucknow Campus for his consistent 
encouragement. We are also thankful to Maj. Gen. K.K. Ohri, Pro VC and Prof. (Dr.)Rajesh 
K. Tiwari, Deputy Director and Head, Amity institute of biotechnology, Amity University 
Lucknow campus, for providing not only help & support but also all necessary facilities to 
conduct the work. 
 
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