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Review Article

Folic acid: A positive inf luence on periodontal


tissues during health and disease
Joann Pauline George, R Shobha1, Flemingson J Lazarus2
Departments of Periodontics, Krishnadevaraya College of Dental Sciences, Krishnadevarayanagar, Hunsmaranahalli, 1M R Ambedkar
Dental College, Bangalore, 2Best Dental College, Madurai, India

INTRODUCTION
ABSTRACT
Periodontal disease is a multifactorial disease, the origin Periodontal health relies on a delicate balance between the
of which remains obscure. However, the manifestation host, environment, bacteria, and other microorganisms.
and progression of periodontitis is influenced by a wide Periodontal disease is the result of complex inter‑relationships
variety of determinants including social and behavioral between infectious agents and host factors. Environmental,
factors, systemic factors, environmental and genetic acquired, and genetic risk factors modify the expression of
factors. Periodontal tissue integrity is dependent on the disease and may, therefore, affect the onset, progression of
adequate intake of proteins, carbohydrates, fats, vitamins, the disease, and the response to treatment.
and mineral salts. Chronic deficiencies in the availability
of one or more of these nutrients are expected to produce Tobacco smoking is one of the age‑old habits and is
pathological alterations in the expression and progression proven to be linked with cancer. It also plays a role as an
of periodontal disease. Folic acid, also known as vitamin B9 environmental factor and is associated with an increased
or folacin, is one such vitamin that is essential for numerous prevalence and severity of periodontal disease and is also
bodily functions ranging from nucleotide biosynthesis to known to negatively influence the levels of nutrition too.
the remethylation of homocysteine. Folic acid deficiency Nutrition is one of the modifiable factors that impact the
causes absence of keratinization of gingival surface, host’s immune response and the integrity of the hard and
decreased resistance to infection, necrosis of gingiva, soft tissues of the oral cavity.[1,2]
periodontal ligament, and alveolar bone destruction in
Periodontal health depends strongly upon an adequate
animals and humans. This may be accompanied by
source of essential nutrients being available to the
ulcerative glossitis and cheilitis. Repair and maintenance
host.[3] The epithelium of the dentogingival junction and
of periodontal tissues generates a high turnover rate of
the underlying connective tissues are among the most
squamous epithelium and without folic acid, epithelial
dynamic tissues in the body. The maintenance of the
cells do not divide properly. Folic acid deficiency is the
healthy periodontium is dependent upon an adequate
most common nutrient deficiency in the world. Organic
supply of proteins, carbohydrates, fats, vitamins, and
nitrites, nitrous oxide, cyanates, and isocyanates found in
mineral salts. Chronic deficiency in any of these nutrients
cigarette smoke have been shown to interact with folic acid,
may be expected to produce pathological alterations in the
transforming them into biologically inactive compounds and
periodontal tissues.[3]
thereby leading to lower folic acid levels in serum, red blood
cells, and respiratory tract. Folic acid supplementation Periodontal disease is the result of an increase in the
as an adjunct in the management of periodontal disease virulence factors of the infecting organisms and the
in smokers will prove to have beneficial effect on the decreased resistance of the host.[4] Nutritional deficiencies
periodontal tissues during repair and turnover.

Key words: End‑organ deficiency, folic acid Access this article online
deficiency, folic acid supplementation, non‑surgical Quick Response Code:
periodontal therapy, periodontal disease, smoking Website:
www.ijhas.in

Address for correspondence: Dr. Joann Pauline George,


DOI:
Department of Periodontics, Krishnadevaraya College of Dental Sciences,
10.4103/2278-344X.120582
Krishnadevarayanagar, Hunsmaranahalli, Bangalore ‑ 562 157, India.
E‑mail: georgedentalclinic@gmail.com

International Journal of Health & Allied Sciences • Vol. 2 • Issue 3 • Jul-Sep 2013 145
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George, et al.: Folic acid and periodontal health

also modify periodontal destruction, but their exact complex includes thiamin, riboflavin, niacin, pyridoxine,
mechanisms have not been precisely defined. Nutritional biotin, folic acid, and cobalamin. Oral changes that
deficiencies may affect any of the basic periodontal defense are common to B‑complex deficiencies are gingivitis,
factors such as the integrity of the dentogingival barrier and glossodynia, angular cheilitis, and inflammation of the
the turnover of its constituent cells.[3] entire oral mucosa.

The B‑complex vitamins, such as niacin, thiamin, riboflavin, Folic acid deficiency results in macrocytic anemia with
folic acid, and B12, are co‑factors in energy metabolism and megaloblastic erythropoiesis, accompanied by oral
are needed in DNA and RNA synthesis. This makes them changes, gastrointestinal lesions, diarrhea, and intestinal
indispensable for tissue maintenance and production of new mal‑absorption.[5] Folic acid‑deficient animals demonstrate
cells during development and healing. The most common necrosis of the gingiva, periodontal ligament, and alveolar
symptom of vitamin B deficiencies is loss of the integrity bone. The absence of inflammation is the result of
of the oral mucosa. The oral manifestations of the loss of deficiency‑induced granulocytopenia. In humans with
integrity include stomatitis, angular cheilitis, and glossitis. sprue and folic acid deficiency, generalized stomatitis
occurs, which may be accompanied by ulcerative glossitis
Vitamin C prevents oxidative cell damage and aids in and cheilitis.[6]
maintaining the integrity of the oral mucosa. Gingival
inflammation appears to be one of the most sensitive Oral disturbances that have been attributed to thiamin
indicators of vitamin C deficiency, which may be related deficiency include hypersensitivity of the oral mucosa;
to the vitamin’s role in maintaining the microvasculature minute vesicles (simulating herpes) on the buccal mucosa,
of the sulcus. under the tongue, or on the palate; and erosion of the oral
mucosa. The symptoms of riboflavin deficiency include
Other nutrients such as proteins, vitamin A, and zinc are glossitis, angular cheilitis, seborrheic dermatitis, and a
important in DNA and RNA replication, transcription of superficial vascularizing keratitis. Niacin deficiency results
RNA, and the translation of proteins and also are necessary in glossitis and stomatitis. The gingiva may be involved
for new cell growth. in aniacinosis with or without tongue changes. The most
common finding is necrotizing ulcerative gingivitis (NUG),
Nutrients function together and nutrient deficiencies rarely usually in areas of local irritation.
occur in isolation, hence it is important to have adequate
supplies of all nutrients to ensure adequate growth and Vitamin C deficiency causes scurvy, characterized by
maintenance of the oral tissues. hemorrhagic diathesis, and delayed wound healing. [7]
Vitamin A deficiency results in degenerative changes in
Purpose of the review epithelial tissues, resulting in a keratinizing metaplasia.
Folic acid deficiency is the most common nutrient deficiency The effect of vitamin D deficiency or imbalance on the
in the world. Organic nitrites, nitrous oxide, cyanates, and periodontal tissues results in osteoporosis of alveolar bone,
isocyanates found in cigarette smoke have been shown to osteoid that forms at a normal rate but remains uncalcified,
interact with folic acid, transforming them into biologically failure of osteoid to resorb, which leads to its excessive
inactive compounds and thereby leading to lower folic acid accumulation; reduction in the width of the periodontal
levels in serum, red blood cells, and respiratory tract. Folic ligament space; a normal rate of cementum formation,
acid supplementation as an adjunct in the management of but defective calcification and some cementum resorption;
periodontal disease in smokers will prove to have beneficial and distortion of the growth pattern of alveolar bone. No
effect on the periodontal tissues during repair and turnover. relationship has been demonstrated between deficiencies in
Hence, a review on the role of gingival health and the vitamin E and oral disease, but systemic vitamin E appears
benefits of folic acid supplementation in deficiency states to accelerate gingival wound‑healing in the rats.
has been discussed.
FOLIC ACID
Vitamins
Vitamins are essential and biologically active constituents Folic acid (also known as vitamin B9 or folacin) and folate
of a diet, which cannot be replaced by other dietary (the naturally occurring form), pteroyl‑L‑glutamic acid,
components.[1] The absence or scarcity of certain vitamins and pteroyl‑L‑glutamate, are forms of the water‑soluble
has been implicated as being etiological factor in the vitamin B9.[8] Vitamin B9 (folic acid and folate inclusive) is
pathogenesis of periodontal diseases.[3] The vitamin B essential for nucleotide biosynthesis to the remethylation

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George, et al.: Folic acid and periodontal health

of homocysteine.[9,10] Homocysteinemia occurs due to prescribed for IBD but also known to inhibit folate
an abnormally high plasma level of homo‑cysteine, the absorption. Evidence suggests folic acid supplementation
de‑methylated derivative of the amino acid methionine, might lower the risk, in a dose‑dependent fashion, of colonic
which is an independent risk factor for cardiovascular neoplasia in patients with ulcerative colitis.
disease. [11,12] Elevated plasma homocysteine has been
connected to increased risk of neural tube defects and The role of folic acid in gingival health and
other birth defects, as well as to schizophrenia, Alzheimer’s disease [Table 1]
disease, cognitive decline, osteoporosis, rheumatoid Folic acid is utilized by virtually all mammalian cells as
arthritis, kidney failure, and cancer.[13,14] a coenzyme for amino acid conversions and synthesis of
pyrimidine and purine needed for deoxyribonucleic acid
T h e a c t i va t e d c o e n z y m e f o r m o f f o l i c a c i d (DNA) synthesis.[1] It is required for cellular division and
(5‑methyltetrahydrofolate) is needed for optimal new cell production. Folate coenzymes function in the
homocysteine metabolism, since it acts as a methyl donor, single‑carbon‑transfer reactions involved in amino acid
providing a methyl group to vitamin B12. The methylated conversions, methyl‑group biogenesis, and nucleoprotein
form of vitamin B12 (methylcobalamin) subsequently formation. At the cellular level, the major defect in folic acid
transfers this methyl group to homocysteine. The result deficiency is an impaired production of deoxyribonucleic
is a recycling of homocysteine to methionine, resulting in acid (DNA) expressed as inefficient mitosis, increase
reduction in elevated plasma homocysteine. in cellular stroma, and asynchronism between protein
synthesis and cell division.[12] Interference with DNA
Folic acid is important during periods of rapid cell division synthesis disrupts the production of messenger ribonucleic
and growth. Both children and adults require folic acid to acid (RNA) and prevents the process of cell maturation
produce healthy red blood cells and prevent anemia. Folate from reaching completion, a factor that would account
and folic acid derive their names from the Latin word folium for the mucosal changes found in the folic acid deficiency
(which means “leaf.”) conditions.[15] Histologically, the most prominent folic
acid deficiency‑related changes were an interference with
Relationship of folic acid and pregnancy the maturation of the epithelial cells, impairment of
During pregnancy, there are increased levels of estrogen keratinization, and an increased susceptibility to ulceration
and progesterone that affects not only the organs of and secondary infection (Dreizen, 1970). Repair and
reproduction but also modifies the reactions of several maintenance of the periodontium generates a high turnover
basic tissues.[13] Hugoson in 1971 has demonstrated a rate of squamous epithelium, thus folic acid is essential
significant correlation between the level of sex hormones for the proper maturation of the rapidly proliferating cells
during pregnancy and the severity of gingival inflammation, (Staats 1965, Gardner 1956). It is thus conceivable that
which was not accompanied by an increase in bacterial gingival epithelium would also be affected in folic acid
plaque. Whitehead in 1973 has suggested that there was a deficiency.
strong interrelationship exists between sex hormones and
folate coenzymes and the rate of folate metabolism may Dreizen in 1970 noted that there were significant
increase in pregnancy. End‑organs may be affected more histopathological changes in folic acid deficiency
severely than other areas, and folic acid too showed a similar marmosets. Histologically, there were thickening of the
end‑organ deficiency without demonstrable evidence of delimiting membrane, finely dispersed and lightly stained
systemic folate deficiency. cytoplasm, lacy appearance of nuclei with fragmentation
and clumping of chromatin, reduction in the number and
Low dietary intake of folic acid increases the risk for size of keratohyaline granules, diminished or completely
delivery of a child with a neural tube defect (NTD). abolished ability to form keratin.
Periconceptional folic acid supplementation significantly
reduces the occurrence of NTD. Each of the folic acid‑deprived marmosets had moderate to
severe generalized gingivitis and periodontitis. Some also
Supplemental folic acid intake during pregnancy results in showed infrabony pocket formation. In these marmosets,
increased infant birth weight and improved Apgar scores.[14] the intestinal villi were thickened, shortened, widened,
branched edematous, occasionally coalescent, and always
Inflammatory bowel disease heavily infiltrated with acute and chronic inflammatory
Patients with inflammatory bowel disease (IBD) often have cells. By comparison, all the marmosets given the daily
folate deficiencies, caused in part by the drug sulfasalazine, dietary supplement of folic acid had an intact mucosa.

International Journal of Health & Allied Sciences • Vol. 2 • Issue 3 • Jul-Sep 2013 147
Table 1: Representing the various facets of folic acid and it’s influence on gingival health and disease

148
Title Journal/authors Experimental design Results
A study was conducted on the Dreizen, Levy and Studies on the biology of the periodontium of Marmoset mucosa has shown to be extremely sensitive
biology of the periodontium Bernick marmosets:VIII. The effect of folic acid deficiency to folic acid deficiency induced experimentally by
of marmosets J Dent Res 1970; on the marmoset oral mucosa dietary and dietochemical means. Histologically,
49:616 the most prominent deficiency related changes was
an interference with the maturation of the epithelial
cells, impairment of keratinization, and an increased
susceptibility to ulceration and secondary infection.
The effect of folic acid on Vogel, Fink, Schneider, Effect of folic acid deficiency on gingival Increased bleeding on probing. Increase in gingival
gingival health Frank, Baker inflammation[16] exudate flow.
J Periodontol. Clinical and histological evidence of severe generalised
1976;47(11):667-8 gingival inflammation
Folic acid deficiency Vogel, Fink, Frank, The effect of topical application of folic acid on Absence of keratinization of gingival surface.
causes[8,15,16] Baker gingival health. Decreased resistance to infection.
J Oral Med 1978; The effect of folic acid on gingival health Folic acid deficient animals demonstrate necrosis of
33:20-22. the gingiva, periodontal ligament and alveolar bone
Vogel, Fink, Schneider, without inflammation. The absence of inflammation
Frank, Baker is the result of deficiency-induced granulocytopenia.
J Periodontol. In humans with sprue and other folic acid deficiency
1976;47(11):667-8 states, generalized stomatitis occurs, which may
be accompanied by ulcerated glossitis and cheilitis.
Ulcerative stomatitis is an early indication of the toxic
effect of folic acid antagonists (e.g. methotrexate) used
in the treatment of leukemia.
Folic acid deficiency has been associated with
abnormalities in rapidly proliferating epithelial cells,
including the buccal squamous cells, junctional
epithelium
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Effects of topical and systemic Thomson and Pack A double blind study was conducted to evaluate The results showed that the group receiving folic
folic acid supplementation on 1980;7 (5):402-414 the effects of topical and systemic folic acid acid mouthwash and placebo tablets showed highly
gingivitis in pregnancy supplementation on gingivitis in pregnancy significant improvement in gingival health in pregnancy
George, et al.: Folic acid and periodontal health

The folate mouthwash Thomson and Pack. J Double-blind study was conducted in order Effects of extended systemic and topical folate
produced highly significant Clin Periodontol 1982; to evaluate the effects of systemic and topical supplementation on gingivitis of pregnancy.
improvement in gingival 9 (3):275-280 folate on gingival inflammation during the fourth
health in pregnancy. and eighth months of pregnancy. Thirty women
were randomly divided into three groups.
Group A received placebo mouthwash and
tablets; Group B: Placebo mouthwash and 5 mg
folate tablets; Group C: Folate mouthwash and
placebo tablets. Supplementation lasted for 14
days during months 4 and 8. Subjects took one
tablet daily and rinsed twice daily for 1 min with
the mouthwash. At the start and finish of each
14-day period, fasting serum and red cell folate
levels were estimated and oral status assessed
by a plaque index, a gingival index, and gingival
exudate flow meter. Subjects completed 1-week
diet sheets which were analysed for dietary folate

International Journal of Health & Allied Sciences • Vol. 2 • Issue 3 • Jul-Sep 2013
(contd...)
Table 1: (Continued...)
Title Journal/authors Experimental design Results
Folate mouthwash: Effects Pack A double blind study was designed to determine Initially, groups were similar except that the
on established gingivitis in J Clin Periodontol the effects of folate mouthwash on established experimental group exhibited more bleeding sites at
periodontal patients 1984;11(9):619-628 gingivitis in non-pregnant adults. Subjects used 5 the outset, but after 4 weeks, the experimental group
ml of mouthwash twice daily for 4 weeks, rinsing showed a significant decrease in mean number of
for 1 min before expectorating. Experimental colour change sites and in bleeding sites compared
mouthwash contained 5 mg folate per 5 ml. The with control group. Dietary analysis showed that
control group used a placebo mouthwash. The few subjects ate>200μg folate daily. However, the
oral examination was repeated after 4 weeks level of dietary folate did not correlate with changes
in inflammation in experimental subjects. Folate
mouthwash appears to have an influence on gingival
health through local rather than systemic influence.
Effects of folate mouthwash Pack Double blind cross-over study study was Folate mouthwash did not appear to have any
on experimental gingivitis in J Clin Periodontol designed to determine whether or not statistically significant effects on accumulated plaque,
man 1986;13 (7):671-676 experimental gingivitis responded to 0.1% folate or clinical signs of experimental gingivitis in this study.
mouthwash in a similar manner to that already The different response of experimental gingivitis to
reported for established gingivitis folate mouthwash, compared with the response of
established gingivitis already reported, further suggests
that experimental gingivitis may not represent an
authentic replica of the cellular and immunological
responses occurring in established gingivitis.
Local and systemic effects of Piyathilake, Macaluso, A study was conducted to investigate the effect Mean plaque index, pocket depth and clinical
cigarette smoking on folate Hine, Richards and of serum levels of folic acid and Vitamin B12 and attachment levels was significantly higher in smoker
and vitamin B-12 Krumdieck hematological indices in smoker and nonsmoker chronic periodontitis patients than non-smoker
Am J Clin Nutr patients with chronic periodontitis chronic periodontitis patients and serum folic acid
1994;60:559–566 concentration was lower in smoker than in non-smoker
patients whereas, blood cell count was higher in
smokers than non-smokers.
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Levels of cigarette Kaldahl, Johnson, Patil, A cross sectional study was carried out among The results suggested lower concentrations of folate
consumption and response to Kalkwarf 39 current smokers and 60 non current smokers and vitamin B12 in current smokers than in non

International Journal of Health & Allied Sciences • Vol. 2 • Issue 3 • Jul-Sep 2013
periodontal therapy J Periodontol 1996; to evaluate the effects of cigarette smoking on smokers.
67(7):675-81 folate and vitamin B12 concentrations in the
circulation
George, et al.: Folic acid and periodontal health

Folic acid, Vitamin B12,and Werscha, Janssensb, A cross-sectional study of 62 smoking and 76 Results showed folate concentrations of the smoking
homocysteine in smoking Zandvoortb. EJOG non-smoking healthy pregnant women. Serum women decreased continuously during pregnancy, and
and non-smoking pregnant 2002;103(1):18-21 folic acid, Vitamin B12 and homocysteine were were significantly lower than those of non-smoking
women measured at four points in pregnancy: 0-10, women during the last 30 weeks. It was concluded that
11-20, 21-30 and 31-40 weeks Smoking women have lower and decreasing folate
levels during pregnancy, possibly as a result of lower
intake of these nutrients. Lower folate levels can lead to
hyperhomocysteinemia, a known risk factor for several
complications in pregnancy.
Effect of smoking on folic Erdemir, Bergstrom A study was conducted to investigate the effect Mean plaque index, gingival index, pocket depth and
acid and vitamin B12 after J Clin Periodontol of cigarette smoking on serum levels of folic clinical attachment levels were significantly increased in
non-surgical periodontal 2007;34:1074-1081 acid and Vitamin B12 in smoker and nonsmoker smoker chronic periodontitis patients than non smoker
intervention patients with chronic generalized periodontitis chronic periodontitis patients, serum folic acid and
after nonsurgical periodontal intervention Vitamin B12 levels gradually and significantly decreased
in smokers than in non smoker patients during a 6
month follow up.

149
(contd...)
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George, et al.: Folic acid and periodontal health

Marmosets deprived of dietary folic acid had an exceedingly

adults and may provide an important clinical target for

Concluding that current smoking status affects dietary


folate levels were found to be lower among smokers.
high incidence of oral infections.

fasting days and dietary micronutrient intake, serum


important indicators of periodontal disease in older
The results suggested that serum folate levels are

The results showed that controlling age, gender,


Keratinization of the cornified mucosa, which is indicative

nutrient intake as well as plasma folate levels.


of cytologic maturity, has been shown to be influenced
by estrogens. A lack of folic acid interferes with estrogen
induced tissue growth and maturation. The susceptibility
intervention to promote oral health.

to oral infection has been attributed to the ensuing


granulocytopenia and anemia that lower host resistance.

Folic acid deficiency


As folic acid deficiency has been associated with
abnormalities in rapidly proliferating epithelial cells,[15] it
is conceivable that the junctional epithelium would also be
affected. The maturation of junctional epithelium, which
Results

has a rapid turnover rate, is a prime importance in the


prevention and control of periodontal disease. Folic acid
deficiency is associated with severe gingival inflammation
(Vogel).[16] Whitehead in 1973 also introduced the concept
to investigate the relationship between smoking
the results showed that a low serum folate level

502 farmers from the Valley of Messara in Crete


was independently associated with periodontal

A cross sectional study was conducted among

of end‑organ deficiency to indicate a relative deficiency of


levels and periodontal disease in older adults,
assess the relationship between serum folate

status and serum and dietary micronutrient

folate occurring in certain tissues despite normal plasma


A cross sectional study was conducted to

folate levels. Vogel in 1976 applied the term “end‑organ


deficiency” in connection with inflammatory changes of
the gingivae, which were responsive to both topical and
systemic folate administration. An end‑organ deficiency
of folic acid can exist even though blood levels are normal.
disease in older adults

Folic acid deficiency in gingivitis patients as compared


Experimental design

to patients supplemented with folic acid have shown to


concentrations

increase bleeding on probing, increase gingival exudate, and


both clinical and histological evidence of severe gingival
inflammation.

Folic acid deficiency leads to absence of keratinization


of gingival surface.[17] Decreased resistance to infection
is also noted among folic acid‑deficient individuals. Folic
J Am Geriatr Soc 2007;
Yu YH, Kuo HK, Lai YL.

Hatzis, Malliaraki, Satis

Tob Induc Dis 2008; 4


Vardavas, Linardakis,

acid‑deficient animals also demonstrate necrosis of the


gingiva, periodontal ligament, and alveolar bone without
Journal/authors

inflammation. The absence of inflammation is the result


and Kafatos
55:108-113

of deficiency‑induced granulocytopenia.
(1):1-7

Smoking and folic acid


Cigarette smoking is one of the factors that negatively
affect the levels of vitamin B12 and folic acid.[11] Active
cigarette smokers have lower folic acid levels in their
examination survey 2001/02
national health and nutrition

serum, red blood cells, and respiratory tract.[12] Cigarette


to serum folate and dietary
older adults: Data from the

Smoking status in relation


Table 1: (Continued...)

The association between

smoking is associated with increased plasma homocysteine


serum folate levels and
periodontal disease in

concentrations and a pro‑ inflammatory and prothrombotic


activity (Heimburger, 1992). Homocysteine is a sensitive
vitamin intake

marker of vitamin B12 and folic acid deficiencies. An


inverse relationship between low folate levels and high
homocysteine levels in smokers is associated with increased
Title

risk of cardiovascular disease.

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George, et al.: Folic acid and periodontal health

Cigarette smoke is known to contain nitric oxide (NO), and maintenance of periodontal health and disease will be
superoxide, and other reactive oxygen species; some of positively influenced by folic acid supplementation.
the adverse effects of smoking may result from oxidative
damage to endothelial cells, which results in nitric oxide Gingival hyperplasia is a common adverse effect of therapy
shortage.[18] During inflammatory reactions, where large with phenytoin. Poor periodontal hygiene is an important
amounts of nitric oxide and superoxide are formed, the risk factor for severity of phenytoin‑induced gingival
combination of both leads to the formation of reactive overgrowth (PIGO), which is a time‑dependent process.
nitrogen species, such as the peroxynitrite anion, a toxic There is complex interplay of altered fibroblast biology,
product of NO when combining with superoxide. The tissue connective tissue turnover, inflammatory processes, and
injury induced by per‑oxynitrite may lead to an excessive growth factors on a background of genetic susceptibility
local amplification of the immune response, resulting in to produce increase in various components of interstitial
migration of inflammatory cells. 5‑methyl tetrahydrofolic matrix in PIGO tissue. There is conclusive evidence that
acid, the active form of folic acid, has shown to reduce folic acid supplementation significantly decreases the
superoxide generation, thus providing antioxidant potential. incidence of PIGO. Oral folic acid supplementation,
On the other hand, free radicals and oxidants, which cause 0.5 mg/day, is associated with prevention of gingival
DNA and membrane damage, are present in high levels in overgrowth in children taking phenytoin monotherapy.[22]
tobacco smoke and may also play a role in decreasing the
folic acid levels. Folic acid supplementation in smokers
It has been seen that among periodontal disease patients,
Organic nitrites, nitrous oxide, cyanates, and isocyanates smokers display significantly reducing levels of folic acid
found in cigarette smoke have been shown to interact with over a period of 6 months after non‑surgical periodontal
folic acid and vitamin B12 co‑enzymes, transforming them therapy.[11,12] Smoking exerted a negative influence on
into biologically inactive compounds. the clinical outcome following non‑surgical periodontal
therapy. With the proven role of folic acid in maintaining
Smoking, folic acid, and periodontal disease the integrity of periodontal tissues and also keeping in
Besides the adverse effects of smoking on immunology mind the rampant alterations it induces to the sensitive
and the host–bacterial interactions, this may account for its physio‑chemical balance at the epithelial‑ connective
deleterious effects on periodontal health;[11] smoking also tissue interface, folic acid supplementation to smokers
negatively affects vitamin B12 and folic acid mechanisms.[12] will be definitely a beneficial therapeutic approach. Any
The deficiency of these vitamins may be detrimental for periodontal treatment in smokers should include effects
the growth and development of the periodontium and to make the patients quit smoking and also include diets
also in the expression and progression of periodontal rich in folic acid, which may prove to be beneficial in
diseases. the post‑therapeutic healing and maintenance. Dietary
supplementation of folic acid can show beneficial effects on
Folic acid supplementation and its influence in the periodontal tissues of smokers with chronic periodontal
gingival and periodontal health and disease disease following non‑surgical periodontal intervention.[11,12]
Folic acid supplementation can be attempted both
systemically and topically.[19] It is available in various forms Future endeavors
like mouthwash, tablets, capsules, and injections. Dietary Epidemiological studies gathering data on association
supplementation of 2 mg systemic folic acid showed an between folic acid, smoking, and periodontal diseases will
increase in the resistance of gingiva to local irritants and help to identify the three pronged association. Randomized
thus led to a reduction in inflammation over a 30‑day clinical trials aimed at folic acid supplementation as an
period (Vogel, 1976).[16] In another instance, the use of 5 ml adjunct to non‑surgical periodontal intervention in smokers
folate mouthwash rinse twice‑daily for 4 weeks for 1 min with chronic periodontitis can be undertaken to justify the
on established gingivitis in non‑pregnant adults showed beneficial effect of folic acid in smoker with periodontal
improved gingival health (Angela R C Pack, 1984).[20] disease.
Systemic folic acid (5 mg/day) in combination with oral
hygiene measures in prevention of phenytoin‑induced CONCLUSION
gingival overgrowth showed that after one year, gingival
overgrowth was delayed in children (Prasad V N, 2004).[21] Folic acid is essential for the maintenance of an intact oral
Evidence such as these present in the literature indicate that mucosa. Folic acid deficiency impairs the maturational
in a folic acid deficiency‑prone situation, the management sequence of the oral mucosal epithelium and depresses

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George, et al.: Folic acid and periodontal health

the hematologic elements that help prevent and combat folate coenzymes by butyl nitrite as observed by NMR: Implications
on one‑carbon transfer mechanism. Biochem Biophys Res Commun
infections in this region. 1986;135:201‑7.
11. Erdemir EO, Bergstrom J. Relationship between smoking and folic
Low levels of serum folate were independently associated acid, vitamin B12 and some hematological variables in patients with
with periodontal disease in older adults; hence, it is chronic periodontal disease. J Clin Periodontol 2006;33:878‑84.
12. Erdemir EO, Bergstrom J. Effect of smoking on folic acid and
quite possible to presume that smoking‑induced folic vitamin B 12 after non surgical periodontal intervention. J Clin
acid deficiency can negatively influence periodontal Periodontol 2007;34:1074‑81.
disease expression and progression. Thus, folic acid 13. Wang G, Dai J, Mao J, Zeng X, Yang X, Wang X. Folic acid reverses
hyper‑responsiveness of LPS‑induced chemokine secretion from
supplementation as an adjunct in the management of monocytes in patients with hyperhomocysteinemia, Atherosclerosis
periodontal disease in smokers will prove to be beneficial. 2005;179:395‑402.
Oral mucosal integrity can be protected by the inclusion of 14. Pulikkunnel ST, Thomas SV. Neural tube defects, pathogenesis and
folate metabolism. J Assoc Physicians India 2000;53:127‑35.
daily supplements of folic acid. 15. Vogel RI, Fink RA, Frank O, Baker H. The effect of topical application
of folic acid on gingival health. J Oral Med 1978;33:20‑2.
REFERENCES 16. Vogel RI, Fink RA, Schneider LC, Frank O, Baker H. The effect of folic
acid on gingival health. J Periodontol 1976;47:667‑8.
1. Nunn ME. Understanding the etiology of periodontitis: An overview of 17. Newman MG, Takei HH, Klokkevold PR, Carranza FA, editors.
periodontal risk factors. Periodontol 2000 2003;32:11‑23. Carranza’s Clinical periodontology. 10th ed. St Louis: Elsevier; 2006.
2. Seymour RA, Heasman PA. Drugs, diseases and the periodontium. 18. Enwonwu CO, Sanders C. Nutrition: Impact on oral and systemic
New York; Oxford University Press; 1992. health. Compend Contin Educ Dent 2001;22:12‑8.
3. Apatzidou DA, Riggio MP, Kinane DF. Impact of smoking on the clinical, 19. Bergstrom J. Cigarette smoking as risk factor in chronic periodontal
microbiological and immunological parameters of adult patients with disease. Community Dent Oral Epidemiol 1989;17:245‑7.
periodontitis. J Clin Periodontol 2005;32:973‑83. 20. Pack AR. Folate mouthwash: Effects on established gingivitis in
4. Grant DA. Periodontics. 6 th ed. St Louis (Washington): Mosby periodontal patients. J Clin Periodontol 1984;11:19‑628.
Company; 1988. 21. Prasad VN, Chawla HS, Goyal A, Gauba K, Singh P. Folic Acid and
5. Bender DA. Nutritional biochemistry of the vitamins. Cambridge, U.K: Phenytoin Induced Gingival Overgrowth‑Is There A Preventive Effect.
Cambridge University Press; 2003. J Indian Soc Pedo Prev Dent 2004;22:82‑91.
6. Folic acid monograph. Altern Med Rev 2005;10:222‑9. 22. Arya R, Gulati S, Kabra M, Sahu JK, Kalra V. Folic acid supplementation
7. Boyd LD, Lampi KJ. Importance of Nutrition for Optimum Health of the prevents phenytoin‑induced gingival overgrowth in children. Neurology
Periodontium. J Contemp Dent Pract 2001;2:36‑45. 2011;76:1338‑43.
8. Volker JF. The relation of nutrition to periodontal disease. J Dent Res
1962;41:264‑78.
How to cite this article: George JP, Shobha R, Lazarus FJ. Folic acid:
9. Piyathilake CJ, Macaluso M, Hine RJ, Richards EW, Krumdieck
A positive influence on periodontal tissues during health and disease.
CL. Local and systemic effects of cigarette smoking on folate and Int J Health Allied Sci 2013;2:145-52.
vitamin B‑12, Am J Clin Nutr 1994;60:559‑66.
Source of Support: Nil, Conflict of Interest: None declared
10. Abu Khaled M, Watkins CL, Krumdieck CL. Inactivation of B12 and

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152 International Journal of Health & Allied Sciences • Vol. 2 • Issue 3 • Jul-Sep 2013

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