Adjunctive Treatment of Chronic Periodontitis With Daily Dietary Supplementation With Omega-3 Fatty Acids and Low-Dose Aspirin

1. Adjunctive Treatment of Chronic
Periodontitis With Daily Dietary
Supplementation With Omega-3
Fatty Acids and Low-Dose Aspirin
Presented by : HEENA
SHARMA

2. Contents
 Introduction
 Materials and method
 Saliva sampling
 Results
 Discussion
 Conclusion

3. Introduction
 Periodontal disease is a local chronic inflammation
initiated by specific microorganisms.
 Tissue destruction is characterized by inflammatory
neutrophil-mediated tissue injury followed by chronic
infiltration of monocytes and the establishment of an
acquired immune lesion.

4.  Although periodontal diseases are associated with
specific pathogenic bacteria, over the last 2 decades,
studies releated the pathogenesis of periodontal
diseases revealed that most of the tissue damage is
caused by the host response to infection and not by the
infectious agents directly.

5.  Accordingly, host modulatory therapy (HMT) has
emerged as a new concept for the treatment of
periodontal diseases.

6. Aim of HMT
 To reduce tissue destruction.
 To stabilize or even regenerate the periodontium by
modifying or downregulating destructive aspects of the
host response and upregulating the protective or
regenerative responses.

7. Goal OF HMT
 To ameliorate excessive pathologically elevated
inflammatory processes.
 To enhance wound healing and periodontal stability
without impairing normal defense mechanisms or
inflammation.

8.  Different drug classes have been evaluated as host-
modulation agents, including
 Non-steroidal anti-inflammatory drugs (NSAIDs).
 Tetracyclines
 Bisphosphonates.

9. NASIDS
 Ciancio in 2002 demonstrated that, NSAIDs either
systemically or topically administrated, have not had
significant clinical applications.
 The magnitude of improvement is measurable.
 But the need for prolonged therapy with the concomitant
risk of adverse side effects limit the use of NSAIDs.

10. Tetracyclins
 Preshaw PM in 2004 demonstratet that,
Subantimicrobial-dose doxycycline therapy that
extended ≥ 3months showed beneficial results when
combined with non-surgical therapy.
 However, there are potential adverse outcomes
inherent in tetracycline therapy, notably photosensitivity.

11. Bisphosphonates
 Kunchur R in 2008 stated that, Bisphosphonates
provide only minor changes in periodontal parameters.
 Their long term use was recently questioned in relation
to the increased risk of osteonecrosis of the jaws after
tooth extraction.

12. Omega-3 Polyunsaturated fatty
acids
 Including docosahexaenoic acid (DHA; C22:6 n-3)
 and eicosapentaenoic acid (EPA; C20:5 n-3),
 They have therapeutic value and anti inflammatory and
protective actions in rheumatoid arthritis, cystic fibrosis,
ulcerative colitis, asthma, atherosclerosis, cancer,
cardiovascular disease, and periodontitis.

13.  The beneficial actions of v-3 PUFAs were attributed, to
a decrease in the production of classic inflammatory
mediators such as arachidonic acid–derived
eicosanoids (prostaglandin E2) and inflammatory
cytokines.
 Charles Serhan et al and Hong et al. demonstrated that
v-3 PUFAs serve as substrates for enzymatic
conversion to a novel series of lipid mediators that were
named resolvins and protectins.
 This new class of bioactive lipid mediators modulate the

14.  Recent studies showed that EPA and DHA (essential v-3
PUFAs), in the presence of aspirin, undergo transcellular
metabolism in human cells to produce a variety of powerful
anti-inflammatory, proresolution, lipid mediators termed 18R-
resolvins and 17R-docosatrienes, respectively.
 These compounds impact several of the functional
responses of isolated polymorphonuclear leukocytes (PMNs)
in vitro and prevent inflammation in a variety of animal
models.
 Aspirin is critical to the enhanced activity of the
stereoisomers (18R- versus 18S-resolvins) through its

15.  The resolvins and docosatrienes are potent natural
resolvers of inflammation in a wide variety of animal
models, including the rabbit model of periodontal
destruction.
 The presence of elevated levels of, or topical treatment
with, these compounds protects the animals from tissue
destruction in a variety of inflammatory- disease
models.

16.  In vitro work in humans demonstrated that these
compounds block superoxide production, chemotaxis,
and transmigration of PMNs from people with diabetes
in vitro upon stimulation with a wide variety of agonists.
 There are also several small experiments in animals
that demonstrated that dietary supplementation with v-3
fatty acids led to a reduction in the progression of
periodontitis.

17. Materials and Method
 Eighty subjects were enrolled in the study from the
Periodontology clinic at the Mansoura University.
 The inclusion criteria for subjects included
 good systemic health
 untreated advanced chronic periodontitis patients of 30
to 70 years of age.
 presence of ≥18 scorable teeth (not including third
molars and teeth with orthodontic appliances, bridges,

18.  Exclusion criteria included
 Systemic illnesses.
 Smoking
 pregnancy or lactation.
 systemic antibiotics taken within the previous 2 months.
 chronic use of NSAIDs.
 confirmed or suspected intolerance to aspirin.
 periodontal therapy within the previous year.

19.  Subjects were divided into two groups (40 patients
each).
 Group 1 was assigned to receive daily placebo
capsules (control).
 whereas group 2 received dietary supplementation with
3 g fish oil and 81 mg aspirin daily following standard
non-surgical periodontal therapy (SRP).
 Each capsule contained 900 mg fish oil (EPA/DHA 30%)
and 100 mg wheat-germ oil.

20.  At the baseline visit, all patients received a complete
dental examination including
 medical history
 dental history
 complete periodontal charting
 panoramic radiographs
 a comprehensive treatment plan.

21.  Clinical measurements included the plaque index
(PI),modified gingival index (GI), BOP scores, PD and
CAL.
 Initial therapy was performed on all patients and
consisted of full-mouth SRP and oral hygiene
instructions were given.
 All initial therapy procedures were performed by the
same periodontist.

22.  The subjects were randomly assigned to receive either
v-3 plus aspirin (v-3 + ASA) or a placebo by a second
periodontist. The randomization was done by the use of
random number charts.
 Clinical assessments at baseline and 3 and 6 months
were made by a third periodontist.

23. Saliva Sampling
 Saliva samples were collected at baseline and 3 and 6
months post baseline.
 Saliva samples were obtained in the morning after an
overnight fast during which subjects were requested not
to drink (except water) or chew gum.

24.  Whole unstimulated saliva samples were obtained by
expectoration into polypropylene tubes
 The saliva samples were weighed, centrifuged to
remove debris, and immediately frozen and stored at -
80C until the sample collection period was completed.
 Inflammation and bone destruction, were evaluated by
determining the salivary levels of biomarkers, MMP-8
and RANKL.

25.  Levels of MMP-8, an important mediator of tissue
destruction in inflammatory Diseases.
 RANKL that promotes bone resorption through the
activation of osteoclasts .
 The level of these biomarkers in saliva were determined
by enzyme-linked immunosorbent assay (ELISA).
 A human-RANKL ELISA development kit§ and an
MMP-8 ELISA development kits were used to quantify
these proteins in the saliva.

26. Results
 Demographic distribution shown no statistically
significant difference in pocket reduction between the
two groups at different time intervals.
 Modified GI scores and bleeding on probing scores
shown no significant difference at different time
intervals.
 There was no statistical difference in PD at baseline. At
3 and 6 months, both groups showed significant
improvement in PDs over baseline measurements.

27.  CAL reductions followed a similar pattern to PD
measurements.
CAL BASELINE 3 Months 6 Months
Test Group 4.5 ± 1.0 mm 2.6 ± 0.9 mm 2.5 ± 1.1 mm
Control Group 4.7 ± 0.1 mm 3.5 ± 1.2 mm 3.4 ± 1.3 mm

28.  Data was further analyzed to determine the distribution
of change in PD and CAL.
 A significant shift to lower PD and CAL gain was noted
for both groups.
% PD < 4 mm 3 Months 6 Months
Test Group 74.7 % 79.5 %
Control Group 49.1 % 54.7 %

29. Biochemical Outcomes
 There was no statistically significant difference between
the two groups at baseline (P >0.05).
 At 3 and 6 months, there was a statistically significant
reduction in RANKL concentrations in saliva in the v-3 +
ASA group (P <0.01).
 At baseline, the MMP-8 level was not different between
groups (P >0.05).

30.  At 3 months, the level was lower for the test group, but
not statistically significant; however, at 6 months, the
level was statistically significantly lower in the v-3 + ASA
group compared to the control group.

31. Discussion
 This study describes the successful adjunctive use of v-
3 + ASA supplementation along with non surgical
treatment of periodontitis, with significantly improved the
outcome of PD and CAL and standard indices as
outcome measures.
 In addition, specific salivary markers of bone resorption
(RANKL) and inflammation (MMP-8) were significantly
reduced in the dietary supplement group.

32.  The molecular basis for the anti-inflammatory impact of
v-3 PUFAs appears to lie in the enzymatic pathways of
the resolution of inflammation.
 The resolution of inflammation is an active process
mediated by metabolism of arachidonic acid by
lipoxygenase transformation circuits leading to the
production of lipoxins: endogenous anti-inflammatory
and proresolution lipid mediators.

33.  These endogenous resolution pathways are enhanced
by the action of aspirin on COX-2.
 Aspirin acetylates COX-2, transforming the enzyme into
an active 15Rlipoxygenase, the product of which, 15R-
HETE, is a substrate for conversion to a 15R- or 15
epilipoxin, which has greater activity than the native
lipoxin because of its extended half-life.

34.  The same enzyme system metabolizes EPA and DHA
into resolvins of the E and D series, respectively, that
are also enhanced by aspirin transformation circuits.
 In this study, the reduction of these two biomarkers
correlated well with clinical improvement after SRP, but
their reduction was enhanced by dietary
supplementation with v-3 PUFAs + ASA.

35.  The impact of v-3 PUFAs, presumably through the
action of the resolvins, on inflammatory biomarkers is :
 the reduction of upstream proinflammatory cytokines
 which directs neutrophils to apoptosis and the non-
phlogistic recruitment of monocytes.
 The ingestion of v-3 PUFAs was shown to increase
circulating levels of resolvins.

36.  Concerns have been raised about the increased risk
of hemorrhage in subjects taking omega -3 PUFA
supplements with or without low dose aspirin .
 U.S preventive services issued a recommendation,
that these compounds should be used with caution
and only in subjects with known risks of
cardiovascular disease or colon cancer.

37. Conclusion
 The results of this preliminary clinical study suggest that
dietary supplementation with v-3 PUFAs and 81 mg
aspirin may provide a sustainable, low-cost intervention
to augment periodontal therapy.
 Future studies need to be done to evaluate the
potential benifit of active metabolites of aspirin modified
omega -3 PUFA in the prevention and treatment of
periodontal disease.