Mouth ulcers – causes & risk factors

Good oral health is one of the main pillars of general health and well-being and World Oral Health Day (WOHD) is celebrated globally in March every year to promote this message.

The World Dental Federation’s definition of oral health is that it is multi-faceted and includes the ability to speak, smile, smell, taste, chew, swallow and convey a range of emotions through facial expressions with confidence and without pain, discomfort and disease of the craniofacial complex (the craniofacial complex comprises the head, face, and oral cavity).¹

There are many factors that can impact oral health and we have discussed some of them in other blogs. In this blog, we review why many people may develop recurrent mouth ulcers which are believed to affect around 20% of the UK population.²

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Infrequent Mouth Ulcers (aphthous stomatitis)

Mouth ulcers are small, painful lesions that develop in the mouth or at the base of the gums.  While mostly harmless*, mouth ulcers can be extremely uncomfortable and make it difficult for some people to eat, drink, and brush their teeth.

*Mouth ulcers that take longer than three weeks to heal should be investigated by a G.P.

Causes

The exact cause of infrequent mouth ulcers varies from person-to-person. There are some common causes and several factors that may aggravate mouth ulcers, including the following:

• biting the tongue or inside of the cheek
• braces, poor-fitting dentures, and other apparatus that may rub against the mouth and gums
• a deficient filling
• stress or anxiety
• medications including beta-blockers and pain killers
• toothpaste which contains sodium lauryl sulphate

Recurrent mouth ulcers (recurrent aphthous stomatitis)

Recurrent aphthous stomatitis (RAS) is an inflammatory, non-contagious condition and is the most common type of ulcerative disease of the oral mucosa. RAS is divided into three categories that relate to the ulcer’s size, the number of ulcers and the healing pattern. In all cases, ulcers are yellow with a red border and are oval or round in shape. These three groups are:

1. Minor recurrent aphthous stomatitis – the most common. They are normally 2mm-10mm in diameter. They usually occur on the lips, cheeks and tongue and heal without scarring.
2. Major recurrent aphthous stomatitis – these ulcers are large and can last from two to six weeks. They can happen anywhere in the mouth including the gums, soft palate (roof of the mouth) and throat.
3. Herpetiform recurrent aphthous stomatitis – these are tiny painful ulcers. Twenty to thirty appear at a time and may join together to form large areas of ulceration.

Discussed below are factors that may lead to the development of RAS:

• Gluten intolerance/coeliac disease
• Female hormonal changes
• Helicobacter pylori infection
• Inflammatory bowel disease
• Vitamin and mineral deficiencies – B12, folate, zinc, iron
• Stress

Gluten intolerance/Coeliac Disease

There are 500,000 people in the UK currently living with undiagnosed coeliac disease. Symptoms often noted include constant mouth ulcers, crippling fatigue, stomach pain, regular bouts of diarrhoea, anaemia and weight loss.³

Researchers studied 247 RAS patients who had at least three aphthous attacks during the year. The team measured antibodies and other immune factors associated with coeliac disease, and patients with negative results were excluded.

Those with positive results underwent biopsies of the lining of the small intestine. Gluten-sensitive enteropathy (coeliac disease) was defined as a positive blood test for immune factors and abnormal biopsy results. A gluten-free diet was recommended for patients with gluten-sensitive enteropathy.

Of the 247 patients, seven patients with positive blood tests underwent upper gastrointestinal endoscopy and duodenal biopsies. Endoscopic findings were compatible with gluten-sensitive enteropathy in two patients and were normal in five patients. However, biopsy findings were compatible with gluten-sensitive enteropathy in all seven patients.  The seven coeliac disease patients had not responded to conventional mouth ulcer medications.

Of the seven coeliac disease patients, four started a strict gluten-free diet. All showed significant improvement within two to six months.

The authors concluded that “Gluten-sensitive enteropathy should be considered in aphthous stomatitis patients”.⁴

It is important to note that people with negative blood tests (for coeliac) may still have the related condition ‘non-coeliac gluten sensitivity’ and this may also be a cause of RAS; therefore, a trial gluten-free diet would be recommended for anyone with RAS where an alternative cause cannot be found.

Hormonal changes

Due to the hormonal changes (particularly the increase in progesterone) that occur during the menstrual cycle, some women experience oral changes that can include bright red swollen gums, swollen salivary glands, development of mouth ulcers, or bleeding gums. During the menstrual cycle, progesterone peaks at around day 10 and drops prior to menstruation. Progesterone has been associated with altered collagen production in the gums and an increase in inflammatory cells.⁵

During menopause one of the main issues is that oestrogen levels start to decrease and this leads to drier mucus membranes in the body, which includes the mouth. Oral discomfort is a common symptom of menopause.⁶

Helicobacter pylori

Helicobacter pylori (H.pylori, a type of bacteria) can infect the stomach and has a tendency to attack the stomach lining leading to stomach ulcers.

The presence of H. pylori in patients with RAS has been analysed, given the histological similarities between this condition and gastric ulcer.⁷  Current studies indicate that H. pylori is present in dental plaque, although the number of organisms in individual samples is very low. The presence of this organism in plaque may be intermittent, perhaps occurring as the result of gastroesophageal reflux. It is still unclear if the low numbers of H. pylori present in the mouths of most patients would be sufficient to serve as a source of infection or reinfection for gastric conditions. Whether dental plaque is a significant source for reinfection of the gastric mucosa among patients with fair to poor oral hygiene remains to be confirmed.⁸

One study found evidence to support the beneficial effect of H. pylori eradication in patients with RAS. One of the mechanisms of H. pylori’s effects is that it reduces vitamin B12 absorption and thus levels of B12 increase after eradication; it also increases free radical production.⁹

Inflammatory Bowel Disease (IBD)

Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), not only affect the intestinal tract but also have an extraintestinal involvement within the oral cavity.

Patients with IBD may present with these oral manifestations years before the appearance of intestinal disease These lesions may occur in 20%-25% of the general population, up to 10% of patients with UC, and 20%-30% of those with CD.¹⁰

Nutrient deficiencies may be the result of intestinal involvement or may be caused by the medications used in the treatment of IBD. Medication often recommended to IBD patients such as sulfasalazine and azathioprine, for instance, may cause folate and niacin deficiency, respectively.¹¹

Vitamin/mineral deficiencies

A variety of underlying disorders may predispose patients to develop RAS. Considering the role of nutritional deficiencies is of utmost importance as RAS may occur with nutrient deficiencies resulting from an insufficient supply of several nutrients.

Vitamin B12

A randomised, double-blind, placebo-controlled trial was carried out on 58 patients suffering with RAS.  Sublingual vitamin B12 was used in patients in the intervention group and a placebo in the control group for 6 months. Approximately three quarters (74%) of the patients of the treated group and only a third (32%) of the control group achieved remission at the end of the study. According to the research: “The average outbreak duration and the average number of ulcers per month decreased in both groups during the first four months of the trial. However, the duration of outbreaks, the number of ulcers, and the level of pain were reduced significantly at five and six months of treatment with vitamin B12, regardless of initial vitamin B12 levels in the blood. During the last month of treatment a significant number of participants in the intervention group reached ‘no aphthous ulcers’ status”.¹²

Whilst this study showed a positive benefit of vitamin B12, regardless of initial B12 status, other studies have reported that there is a clear relationship between recurrent aphthous ulcers and a deficiency of vitamin B12.^13,14 It may be that those patients considered within the normal range for B12 had levels that functional medicine practitioners would consider sub-optimal.

Vitamins B1, B2 and B6 Deficiency

In a study evaluating the thiamine, riboflavin and pyridoxine (vitamin B1, B2 and B6) status of 60 patients with recurrent mouth ulcers, 17 patients (28.2%) were found to be deficient in one or more of these vitamins. Replacement therapy of these vitamins was given to a study group of deficient patients and a non‐deficient group for one month. At the end of therapy and after a follow‐up period of three months, only those patients who had a B complex deficiency had a significant sustained clinical improvement in their mouth ulcers. The study concluded that vitamin B1, B2 and B6 deficiencies should, therefore, be considered as another possible precipitating factor in RAS.¹⁵

Homocysteine, iron, vitamin B12 and folic acid status

One study evaluated whether there was a close association of deficiencies of haemoglobin, iron, vitamin B12, and folic acid and high blood homocysteine level with RAS and levels of these were measured in 273 RAS patients and compared with the corresponding levels in 273 age and sex matched healthy control subjects. The results showed 21 (7.7%) RAS patients had an abnormally high blood homocysteine level. RAS patients had a significantly higher frequency of haemoglobin, iron, vitamin B12, or folic acid deficiency and abnormally elevated blood homocysteine level than healthy control subjects.

The study concluded that there was a significant association of deficiencies of haemoglobin, iron, vitamin B12, and folate, and abnormally high blood homocysteine level with RAS.¹⁶

It is important to note that homocysteine is an amino acid, the metabolism of which is linked to that of several vitamins, especially folic acid, B6, and B12. A high concentration of homocysteine in the plasma is linked to vascular disease, including stroke. Concentrations of homocysteine can be lowered using a combination of folate, vitamin B12, and vitamin B6.¹⁷

Other studies support the theory that RAS is a multifactorial disease with common suspected aetiologies of B12 and folic acid deficiency as well as iron deficiency anaemia.^18,19

Omega 3

Omega-3 fatty acids play an essential role in the functioning of all cell membranes throughout the body. They provide the initial starting point for hormones that regulate the relaxation and contraction of artery walls, inflammation and blood clotting.

Research has shown that omega-3 fatty acids contribute to a reduction in inflammation. A six-month double-blind clinical trial was carried out on 50 patients with RAS, who were randomly divided into the omega-3 group and placebo group. The number of ulcers in the group receiving omega-3 supplements reduced significantly in the fifth and sixth months in comparison with the placebo group. Thus this study concluded that omega-3 consumption decreased the symptoms of RAS.^20,21

Zinc

Zinc is a foundational mineral that is essential to human growth patterns and has an essential role in the development of hormones and immune molecules. It is a mineral that the body uses for fighting off infections and producing cells. Zinc deficiency affects the skin and gastrointestinal tract, the brain and central nervous system, immune, skeletal, and reproductive systems.

In the mouth, zinc deficiency can manifest as non-specific oral ulceration.  A number of studies using zinc therapy have successfully eradicated or reduced symptoms of RAS.^22–24

Stress

Some studies have suggested that psychological disturbances such as stress and anxiety could play a role in the onset and recurrence of RAS lesions, though results have been rather varied.

However, a study in 2009 conducted a case-control investigation on the influence of psychological stress on RAS onset. This was done using an internationally validated questionnaire that evaluated the patients’ level of stress by assessing the presence, frequency and intensity of stress symptoms. It concluded that psychological stress may play a role in the manifestation of RAS; it may serve as a trigger or a modifying factor rather than being a cause of the disease.²⁵

Other studies have also come to the same conclusion and this suggests that stress can be a risk factor, thus, stress-management interventions may be beneficial in reducing RAS recurrence episodes.^26,27

Mouth Cancer

Be aware that mouth ulcers, which don’t heal within three weeks, may be a symptom of mouth cancer and should always be in investigated by your G.P.

Other symptoms, listed on the NHS website, include:

• unexplained, persistent lumps in the mouth that don’t go away
• unexplained, persistent lumps in the neck that don’t go away
• unexplained looseness of teeth, or sockets that don’t heal after extractions
• unexplained, persistent numbness or an odd feeling on the lip or tongue
• sometimes, white or red patches on the lining of the mouth or tongue – these can be early signs of cancer, so they should also be investigated
• changes in speech, such as a lisp
• and others

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If you have any questions regarding the topics that have been raised, or any other health matters please do contact me (Jackie) by phone or email at any time.

jackie@cytoplan.co.uk, 01684 310099

Jackie Tarling and the Cytoplan Editorial Team

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References

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4. Shakeri R et al (2009) Gluten sensitivity enteropathy in patients with recurrent aphthous stomatitis. BMC Gastroenterol, 9(1):44.
5. Markou E et al (2009) The influence of sex steroid hormones on gingiva of women. Open Dent J. 3:114-119.
6. Wardrop RW et al (1989) Oral discomfort at menopause. Oral Surgery, Oral Med Oral Pathol. 67(5):535-540.
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9. Arslan Taş D et al (2013) Impact of Helicobacter pylori on the clinical course of recurrent aphthous stomatitis. J Oral Pathol Med. 2013;42(1):89-94.
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16. Sun A et al (2015) Significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high homocysteine level with recurrent aphthous stomatitis. J Oral Pathol Med. 44(4):300-305.
17. Schwammenthal Y, Tanne D (2004) Homocysteine, B-vitamin supplementation, and stroke prevention: from observational to interventional trials. Lancet Neurol. 3(8):493-495.
18. Wray D (1975) Recurrent aphthae: treatment with vitamin B12, folic acid, and iron. Br Med J. 2(5969):490-493.
19. Nurdiana D, Astari P (2018) The Relationship between Recurrent Aphthous Stomatitis and Iron Deficiency Anemia. In: Proceedings of the International Dental Conference of Sumatera Utara 2017 (IDCSU 2017). Paris, France: Atlantis Press;
20. El khouli AM, El-Gendy EA (2014) Efficacy of omega-3 in treatment of recurrent aphthous stomatitis and improvement of quality of life: a randomized, double-blind, placebo-controlled study. Oral Surg Oral Med Oral Pathol Oral Radiol. 117(2):191-196.
21. Nosratzehi T, Akar A (2016) Efficacy of Omega-3 in Treatment of Recurrent Aphthous Stomatitis: A Randomised, Double-blind, Placebo-controlled Study. Chin J Dent Res.
22. Merchant HW (1977) Zinc sulfate supplementation for treatment of recurring oral ulcers. South Med J. 70(5):559-561. http://www.ncbi.nlm.nih.gov/pubmed/870981. Accessed February 21, 2019.
23. Orbak R (2003) Effects of zinc treatment in patients with recurrent aphthous stomatitis. Dent Mater J. 22(1):21-29. http://www.ncbi.nlm.nih.gov/pubmed/12790293. Accessed February 21, 2019.
24. Endre L (1991) Recurrent aphthous ulceration with zinc deficiency and cellular immune deficiency. Oral Surg Oral Med Oral Pathol. 72(5):559-561. http://www.ncbi.nlm.nih.gov/pubmed/1745514. Accessed February 21, 2019.
25. Gallo C de B, (2009) Psychological stress and recurrent aphthous stomatitis. Clinics (Sao Paulo). 64(7):645-648.
26. Huling LB (2012) Effect of stressful life events on the onset and duration of recurrent aphthous stomatitis. J Oral Pathol Med.41(2):149-152.
27. Abdullah MJ (2013) Prevalence of recurrent aphthous ulceration experience in patients attending Piramird dental speciality in Sulaimani City. J Clin Exp Dent. 5(2):e89-94.

Last updated on 20th October 2022 by cytoffice