Oral Medicine

ORAL MANIFEflTATIONS OF VITAMIN DEFICIENCIES

Review Article

C. A. MEDINA, D.D.S., SANTURCE,PUERTO RICO

Introduction

NUTRITIONAL deficiencies cause numerous conditions which affect the

human organism and many of the lower species. The science of nutrition
could be defined as the study of the dietary requirements of the individual, as
well as the storage, absorption, and the utilization of the absorbed food factors
by the tissues. This field of study has developed extensively during the last
few decades, attaining great importance in the differential diagnosis and treat-
ment of many conditions. Deficiency conditions, which were very dil3lcult to
treat a few years ago, are now being successfully eliminated by the addition
of the constituents lacking in the diet of the individual. Nutritional de-
ficiencies can be caused by an inadequate diet, by disturbances in the intake,
absorption, and utilization of those factors essential for the organism, and by
those conditions in which there is an increase of the nutritional requirements
of the body and/or an abnormal destruction or excretion of these essential
food factors. The patient might be consuming an adequate diet and the
absorption and utilization might be normal, but he still experiences the nutri-
tional deficiency. Among the physiologic states and diseases that may serve
as conditioning factors for a nutritional deficiency, we find pregnancy, high
environmental temperatures, hyperthyroidism, fever, and high carbohydrate
diets. According to Burket,l “ lead poisoning, alkali therapy, and the admin-
istration of antibiotics and sulfonamides may result in increased destruction
of the dietary essentials.” The nutritional requirements of the individual
also may be increased by an excessive excretion of the various factors from
the body.
Nutritional deficiencies have been divided into two groups: primary and
secondary. The primary nutritional deficiency results from an inadequate
dietary intake. The secondary nutritional deficiency (also known as “condi-
tioned”) results from a number of factoral Among these predisposing or
conditioning factors, we find : (a) diseases associated with an increased
metabolic rate, (b) diseases which interfere with the absorption of the dietary
1060
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essentials, (c) lack of hydrochloric acid in the stomach, (d) any functional ol
organic gastrointestinal disorder, and (e) increased excretion of t.he essential
factors. Nutritional deficiency, as such, is a systemic disorder. Demonstrabh
lesions due to the same might be limited to one region of the body, eve11
though the condition is systemic in nature. The chemical or cellular drficienc*y
appears in t,he individual long before the tissue changes can be recognized
clinically. Nutritionists have agreed t.hat deficiencies almost always develop
gradually and run a chronic course. “The acute states are esacerhations of
the chronic deficiency.“”
According to Follis,s the physiologic and pathologic changes which I’+
suit from deficiencies of essential nutrients follow an orderly sequence of
events. He describes this as follows: (a) decreased concentration of the
essential nutrient. in the blood and intercellular fluid, (b) decreased inter-
cellular concentration in one or more tissues, (c) physiologic changes in such
tissues, followed by (d) pathologic alterat.ions which are first seen microscop-
ically and then become grossly visible. It does not. hold true that this sequence
takes place in every case or is carried t.o completion in every inst.ance.
Clinical nutritional deficiencies are almost always multiple. Thorna states
that “patients suffering from multiple defieieneies show? on administratiorl
of one of the factors, prompt improvement in the lesions diagnostic oE the
syndrome for which the drug is specific, but not of the lesions of assorittted
syndromes. ’ ’ A deficiency in one nutrient may predispose to a deficiency iu
others.
Vitamins
The human organism is unable to synthesize a number of substances which
possess unique molecular structures and are essential components of the
chemical machinery of the cell5 These substances are known as vitamins.
FollisS defines a vitamin as an organic substance, soluble in fat or water.
which ordinarily is needed only in minute quantities to maintain the metabolic
integrity of certain cells and tissues. According to this definition, vitamins
are divided into t.wo groups: fat-soluble vitamins and water-soluble vitamins.
The fat-soluble group of vitamins was discovered during the second decade of
this century. McCollum and Davis3 and Osborne and Mende13 demonstrated
a material that promoted growth in animals which had been placed on purifietl
diets. This material was named vitamin A. A second fat-soluble vitamin.
vitamin D, was demonstrated by McCollum in 1922. The existence of a third
member of this group was demonstrat.ed in the same year by Evans and his
co-workers,3 namely, vitamin E. It was not until 1932 t.hat t,he fourth member.
vitamin K, was discovered.5
The water-soluble group of vitamins made their appearance in the litera-
t,ure in 1915, with the introduction of vitamin B by McCol1um.s The functions
of this group of vitamins are better understood tha,n t,he functions of the fat-
soluble group. Some of them have been shown to act as parts of eoenxymcts
1062 MEDINA 0. S., 0. M., & 0. P.
October. 1956

in biologic processes. Vitamin C or ascorbic acid, which is the essential factor

lacking from the diet in the deficiency disease known as scurvy, stands apart
biologically from the above vitamins.
Patients with clinical nutritional deficiencies are primarily medical prob-
lems. In dealing with these patients, the dentist is responsible for the recogni-
tion of the early lesions associated with the nutritional disorders, especially
those manifested in the mouth. It is also part of his responsibility to correct
any oral disease which might interfere with an adequate dietary intake.

Oral Manifestations
Vitamin A.-This vitamin was first reported by McCollum and Davisa and
by Osborne and Mende13 in 1913. They observed that animals (rats) failed to
grow in a normal fashion in the absence of this substance. Carotene was sug-
gested as the active principle of vitamin A a few years later. Finally, in
1930, carotene was shown by Karrer* to be provitamin A. The presence of
bile and a certain amount of fat is essential for the proper absorption of
this substance from the animal’s intestinal mucosa. The vitamin A reserve of
the body is stored in the liver, where the conversion of provitamin A
(carotene) into vitamin A is supposed to occur.
The most characteristic effects of vitamin A deficiency are produced on
certain epithelial structures of the body. The epithelial tissues which under-
go atrophy and which are replaced by stratified keratinizing epithelium are
those which have a secreting function in addition to the role of a covering
layer.’ The salivary glands show keratinizing metaplasia of their constituent
epithelial tissues in vitamin A deficiency.
Marked effects on the incisor teeth of rats and guinea pigs have been
observed in vitamin A deficiency, as these structures continue growing
throughout the life span of the animal. The enamel organ of the forming
tooth, being an epithelial structure, undergoes atrophy and keratinizing
metaplasia. Boyle6 has described changes in the enamel organ of tooth germs
in human infants with vitamin A deficiency comparable to the changes in
rodent intiisor teeth. This enamel hypoplasia observed in rodent incisor teeth
manifests itself as tears, canal-like defects, or deeply stained interprismatic
substances7 Leach8 states that ‘La deficiency in the food elements which con-
tain vitamin A appears to exert a deleterious effect on the periodontal
tissues. ” Mellanby and King’ found that puppies fed a vitamin A-deficient
diet develop hyperplasia of the gums, gingivitis, and pyorrhea.
Vitamin D.-In 1922 Vitamin D was found by McCollum3 to be a different
substance from vitamin A. The most important forms of the vitamin are
activated ergosterol (viosterol or calciferol) and activated cholesterol (7-
dehydro-cholesterol). Both forms are used in the prophylaxis, treatment, and
therapy of rickets. The antirachitic factor is obtained by means of the activa-
tion of provitamins in the skin by the action of ultraviolet light.
A vitamin D deficiency in the organism will lead to the development of a
condition known as rickets. Vitamin D is concerned with the regulation of
Volume 9 ORAL MANIFESTATIONS OF VITAMIN DEFICIENCIES 1063
Number IO

the calcium and phosphorus in the body. The pathogenesis of rickets lies
in the concentration of the calcium and the phosphate ions in the blood serum.
According to Follis,3 vitamin D enhances the absorption of calcium from the
intest.inal tract, but phosphorus absorption appears to be unaffected by the
presence or the absence of the vitamin.
Vitamin D deficiency will produce changes in the bone structure and the
developing teet.h. In bone the most marked effect is the failure of cakifh-
t.ion of the bone matrix. The organic matrix is deposited upon pre-existing
bony trabeculae in a normal fashion, but calcium and phosphorus fail to be
deposited in t.his organic matrix. According to Duncan,g the primary fault
is in the body fluids, which do not make bone salts available to the bone. In
teeth, there is a retardation in predentine formation, as well as a pronounced
disturbance in t,he aalcification of all the dentine which is formed. A line elf
disturbed calcification appears in the dent.ine.0 Recause of defective calcifie:1-
tion of dentine and enamel, and some a.trophy to the odontoblasts and the
enamel organ, hypoplastic teeth usua.lly develop when the condition (rickets)
exists during the formative periods of t.he teeth.
Vitamin C (Ascorbic Acid).-This vitamin was synthesized in 1933 by
Reichstein, Grussner, and Oppenauer.” Tt is related to the metabolism of
aromatic a.mino acids, phenylalanine, and tyrosine, as well as to the succinic
dehydrogenase activit.y of heart and skeletal muscles, and to blood fibrinogen
production. It, is relat.ed also to t,he secretion of intraocular fluid.1°
According to Dunean,s vitamin C is essential for t.he maintenance of nor-
mal intercellular material of connective tissue. bones, teeth, and blood vessels.
Rurket* states that “ascorbic acid is essential for t.he development. of the inter-
cellular subst,ance (collagen) of connective tissue, the osteoid of bone and t,h(b
dent.ine of t&h. It is also related to a hemorrhagic phenomenon which may
be due to a defect. in the cementing substance of the capillary epithclium.”
The mechanism by which this vitamin promotes the formation of collagcnou~
intercellular substances is not known. In the scorhutic stat.e, the healing
process is disturbed. Vitamin C appears to 1~1essentia.1for the healing process
in any pa,rt of the body.
The clinical condition produced by vit.amin C deficiency is known as
seurvy. Its oral symptoms consist of enlarged, spongy, bluish red gingival
tissues. The gums usually bleed on slight pressure and it is common to hn.vc!
loose teet.h. Secondary fusospirochetal infection accompanies the condition
quite frequently, producing a foul odor. Submucosal hemorrhages arc ob-
served anywhere in the mouth. According to Hirschfeld,ll in the scorbutic
state the gingivae change from a normal pink color to old rose and fina.lly to
purple or dark blue or even black. Hematomas may develop as a. result. of
submucosal hemorrhages. Limited studies by Roth’ seem to indicate that
vitamin C deficiency is one of the causes of periodontal conditions in human
beings. Rosenblum and Jolliffel* state, “The gingival lesions seen in vitamin
C deficiency are due to a vascular diathesis which produces swollen am1 boggy
gums that bleed easily a,nd progress to actual ulceration.”
 MEDINA 0. s..0. M..&0. I’.
Octdxr,1950
The Vitamin B Complex.-The vitamin B complex consists of a group of
vitamins closely related to each other, which are essential for the normal func-
tioning of the body tissues. Their exact chemical composition is not very well
known, and further study is needed to determine the nutritional values of
some of the members of the complex. A diet deficient in one of the factors of
this group is almost certain to be deficient in others. According to Burket,l
some of the members of the complex are related to cellular respiration and
nutrition. Gorlin and Levy13 observed, in rats deficient in vitamin B complex,
microscopic changes which took place in the temporomandibular joint during
the deficiency state.
Thiamine : According to Burket,l the function of thiamine in tissue respira-
tion is to aid the tissues in the utilization of pyruvic acid in the normal respira-
tory process. Duncan9 states that “in its biologically active form, ,thiamine is a
co-enzyme which acts as a catalyst, in combination with a specific protein, in the
removal of pyruvic acid derived from lactic acid in carbohydrate metabolism.”
Thiamine deficiency leads to the development of the clinical condition
known as beriberi, in which a severe multiple neuritis is the characteristic
clinical feature. The oral lesions associated with the deficiency are not very
severe. There are enlargement and edema of the tongue, loss of the normal
muscle tone, and slight involvement of the fungiform papillae, which are en-
larged, edematous, and hyperemic. Roth7 has suggested that thiamine de-
ficiency may be related to the development of aphthous lesions and herpetic
vesicles in the oral cavity.
RiboflaGn: In 1932 Warburg and Christian3 isolated a respiratory pig-
ment which later was shown to be the vitamin now known as riboflavin. The
prosthetic group of this vitamin is the riboflavin 5-phosphate, which is closely
related to the enzymes that function as hydrogen carriers in the metabolic
reactions of the body. According to Duncan,B the “yellow enzyme” of War-
burg and Christian (riboflavin) is present in all types of living cells, where it
functions as an oxygen carrier between molecular oxygen and the substrate
in association with other oxidative systems.
The oral lesions produced by riboflavin deficiency can be divided into
three headings :
1. Angular stomatitis, which is the most common and character-
istic manifestation of riboflavin deficiency. The first sign of the
condition is a change in color of the mucosa of the labial commissures,
followed by pallor and then maceration. The patient usually feels
pain on opening his mouth. At a later stage the corners of the mouth
appear grayish white and moist. In more advanced stages, the epithe-
lium shows cracks which extend into the underlying tissues. Sec-
ondary infection is likely to develop at this stage of the condition.
2. Cheilitis. Sydenstricker and associates” say that “the most com-
mon lesions consist of redness, desquamation, and finally ulceration of
Volume 9 ORAL MANIFEHTATIONH OF YIT.GflK DEFWIEN(‘[EB 1065
Numher 10

the lips at the muco-cutaneous junction with fissures at the corners of

the mouth.” The lips are usually excessively dry and wrinkled. AC-
cording to Afonsky,2 there is some exfoliation of the superficial epithe-
lium of the lip, giving the lip an uneven and patchy or mottled appear-
ance. Superficial or deep fissuring is observed in the more advanced
stages of the condition. The lesions now described as cheilitis or
angular stomatiCs are very similar to those formerly described as
per&he.
3. Glossitis. Afonsky2 describes this condition as follows: “The
surface of the tongue assumes a magenta color. The whole dorsum
of the tongue is uniformly colored and dry, having a complete absence
of coating. The tongue assumes a p&bZl/ or cobblestone appearance
due to the projection of small bulbs of fungiform papillae over the
surface of partially atrophic filiform papillae.” Pain is usually
absent in this condition.
Nicotinic acid: Nicotinic acid was prepared synthetically in 1867, but it
was not until 1935 that it became important from a nutritional st.andpoint.
In 1935 nicotinic acid was shown to be a very important constit.uent of co-
rnzymes I snd II, which act as hydrogen carriers in cell respiration. Nicotinic
acid and its amide (niacinamide) were found effective in the treatment of
black tongue in dogs.3 As a result of this observation, both substances havcl
been widely used in the t,reatment of pellagra in man.
The clinical condition produced by nicotinic acid deficiency is known as
pellagra. 1t.s characteristic lesions are changes in the skin, in the tongue a.nd
buccal cavity, in the esophagus and colon, and in the nervous system. It oc-
curs in persons of either sex at any age. The lesions produced on the II’IUCOUS
membranes of the tongue and oral cavity by thr, deficiency are usually the
earliest lesions of diagnostic value. According to Rurket,l clinical manifcst.a-
tions associated with other nutritional deficiencies arc sometimes observed in
a pellagrous patient.. Thus, we may have patients showing lesions of bcribrri.
riboflavin deficiency, scurvy, or vitamin A deficiency at the same time.
The oral manifestations of niacin deficiency arc remarkable. The niarill
deficiency state is divided into acute and chronic! processes. The acut(b
process appears very rapidly, runs a rapid course, and shows a marked r+
sponso to therapy. The pathologic lesions are first seen on the tip, then. sprca(l
t.o t.he lateral borders, and finally to the dorsum of t.he tongue. Krause* ih*-
scribes t.hc principal pathologic changes of t.hn acute state as Eollows:
“vascular hyperemia and proliferation, hypertrophy and then extinction 11f’
the papillae, predominated by affecting the fungiform papillae and, to a I~FWI
extent, the filiform papillae ; redness, swelling, and hypertrophy of the tongut> :
indentations of the borders of the tongue; atrophy of the papillae itnpa.rt.ing
to the t,ongue a red and smooth surface, the so-called cardinal or bald tongue
usually in its most striking form in acute pellagra ; ulcers and erosions. ” The
most common lesions are hyperemia, engorgement, and hypertrophy of t h(\
fungiform papillae. Intensity of the n~utc~ process is indicated by the
1066 MEDINA 0. S., 0. M., & 0. P.
October. 195fD

development of ulcers and eroded areas. According to Afonsky,z thesct

ulcerations and erosions are “superficial, irregular in shape, sharply dema1*-
eated, grayish or red in color, and may be covered with bloody crusts. ‘? The
chronic state is characterized, according to Krausq2 by vascul.ar hyperemin
and proliferation, infiltration, and atrophy of t,he papillae. The tongue does
not show the characteristic redness of the acute statq but. shows fissures,
crevices, and the loss of substance. These crevices appear as deep, clean-cut,
linear depressions, with bright red surfaces, thus giving t.hc tongue the ap-
pcarancc of raw meat. lpissure formation usually follows the invagination
and wrinkling of the surface of the dorsum of the tongue. Muscular atrophy
of the tongue develops in the late st.ages of t.he chronic state.’ As described
by Afonsky,2 “ the tongue shrinks and s.ppears small, thin, smooth, and
glazed, and becomes painful.”
Tho borders of the tongue are usually involved in both the acute and
chronic states. The edematous condition which dovelops causes an increase
in the bulk of the tongue. Excessive pressure of the tip and lateral margins
of the tongue against the teeth resu1t.s in markings or indentations in fhcsc
regions.
The action of the vitamin B complex group on the gingivac and the sup-
porting dental tissues is not very well known. Some of these vitamins arc
essential for the maintenance of the tissues of the body, so it is possible to
assume that any deficiency of the vitamin B complex group might be responsible
for pathologic changes in the supporting tissues of the teeth. Beck9 observed
that nicotinic acid deficiency in dogs results in inflammation of the gingivae.
According to Afonsky,2 hyperemia of the dental and parodontal tissues, fol-
lowed by osteoporosis of the supporting bones, results in cases of deficiency
of the filtrate portion of the vit.amin B complex.
Clinically Less Well-Known Vitamins.-Some of the vitamins to be dis-
cussed in this section have ~WJI proved essential for ot.her spccics, but. not for
man.
1. Pvridotine .(&an& B6): According to Burket,l pyridoxine probably
plays a role in the metabolism of amino acids and pyruvates. Gorlin and
LevyI found that pyridoxine deficiency in mice showed a cessation of growth
of t.he mandibular condyle, regressive changes in the alveolar bone, and ulcera-
tion of t.he epithelium of the interdental papillae. Pyridoxine seems to be
related to the development of angular cheilosis, as some patients who fail to
respond to riboflavin therapy improve readily following the administration of
pyridoxine. Mueller and VilteP observed, in human patients placed on a
pyridoxine-deficient diet, swelling and reddening of the tongue and buccal
mucous membranes which resembled the glossitis of niacin deficiency. The
glossitis, stomatitis, and cheilosis that developed failed to respond to nia-
cinamide, thiamine, and riboflavin therapy, but responded to pyridoxine ad-
ministration.
 2. Pantothenic acid: The physiologic and functional importance of this
vitamin in human beings is not very well known. No oral manifestations have
been observed as a result of a deficiency state in human beings. Levy* found
that pantothenic acid deficiency in mice was associated with resorption of the
alveolar bonr and proliferative changes in the oral mucosa.
2. Folic acid: The clinica. condition associated with folic acid deficiency
is sprue. The oral lesions of sprue are very prominent.. Burket’ describes the
oral lesions as follows: “The patient complains of a burning sensation of the
oral mucosa and the tongue. Numerous minut.e herpetic vesicles form and
soon rupture, leaving painful superficial erosions. The tongue becomesswollen
and the fungiform papillae become enlarged and usually prominent. Angular
rheilosis is also common.” Following the administration of folic acid, t.he oral
symptoms disappear within three to four days.
4. Choline, biotin, inositol, and para-aminobenzoic acid: No oral lesions
hay-ebeen reported in cases in which a deficienc.y of these vitamins wa,spresent.

S-
The science of nutrition has attained a great importance in the last few
decades. The diet of the individual is of extreme importance in the main-
tenance of healthy tissues and in the prevention of nutritional deficiencies.
Inadequate diet and disturbances in the absorption, utilization, destruction. 01
excretion of certain essential factors present in the diet are the main causes
of nutritional deficiencies. There are also a number of diseases and physio-
logic st,ates which will render the individual unable to use the essential factors
of a normal diet, even when they are present in adequate quantities. Nutri-
tional deficiencies have been divided into primary deficiencies (which result.
from an inadequate dietary intake) and secondary deficiencies (which result,
from a number of predisposing or conditioning factors). Cl.inical nutrit.ional
deficiencies are almost always multiple.
Among the essential factors present in the diet, we And a group of snb-
stances known as vitamins. These substances arc very important for the
t.issues, as they are related to t.issuc respiration and other biologic processes.
Jn the absence of some of these vit.amins from t,ht! diet., deficiency states dc-
v&p which show characteristic lesions in the oral tissnc>s.
References
1. Uurket, I,. W.: Oral Medicine, ed. 2, Philadelphia, 1952, .T. B. Lippincott Company.
2. Afonsky, D.: Oral Aspects of Vitamin R Complex Deficiency, ORAL Sm., ORAL MII).,
AND OVAL PATH. 3: 1299,195O.
3. Follia, R. H.: The Pathology of Nutritional Disease, Springfield, Ill., 1948, Charles (I
Thomas.
-I. Thoma, E. H.: Oral Pathology, ed. 3, St. Louis, 1950, The C. V. Mosby Company.
5. Wolbach, 5. B., and Bessey, 0. A.: Tissue Changes in Vitamin Deficiencies, Physiol.
Rev. 22: 233, 1942.
0. 13oyle, P. E.: Manifestations of Vitamin A Deficiency in a Human Tooth (fsnn? ;I. 1).
Res. 13: 39,.1933.
7. Roth, H.: Nutrition and Oral Conditions, J. 13. Med. S: 5, 1953.
8. Leach, T. A.: The Use of Vitamin A in the Treatment of Periodontoclasin. .I.
Periodont. 25: 53, 1954.
1068 MEDINA 0. s.. 0. ill., 8i0. P.
October. 1936

9. Duncan, G. G.: Diseases of Metabolism,. Philadelphia, lQ48, W. B. Saunders Company.

10. Friedenwald, J. S., Buschke, W., and Mmhel, Ii. 0.: Role of Ascorbic Acid (Vitamm
C) in Secretion of Intraocular Fluid, Arch. Ophth. 29: 535, 1943.
11. Rirschfeld, I.: Scurvy, A Report on Three Cases in Adults, J. Am. Dent. A. 16: 796,
1929.
12. Rosenblum, L. A., and Jolliffe, N.: The Oral Manifestations of Vitamin Deficiencies,
J.A.M.A. 117: 2245, 1941.
13. Gorlin, R. J., and Levy, B. M.: Changes in the Mandibular Joint and Periodontium of
Vitamin B Complex Deficient Rats and the Course of Repair, J. D. Res. 30: 337,
1951.
14. Sydenstricker, V. P., Geeslin, L. E., Templeton, C. 1X., and Weaver, J. W.: Ribo-
flavin Deficiency in Human Subjects, J.A.M.A. 113: 1697, 1939.
15. Mueller, J. F., and Vilter, R. W.: Pgridoxine Deficiency in Human Beings Induced
With Desoxypyridoxine, J. Clin. Invest. 2Q: 193, 1950.
125 NEPTUNE ST;
ATLANTIC VIEW.