Original Research
`
`Evaluation of the Effects of Neptune Krill Oil
`
`on Chronic Inflammation and Arthritic Symptoms
`
`Luisa Deutsch M.D., M.Sc.
`
`D8p£ll’l|‘ilel‘Il ofBehaviora| Science and Health Research, University Health Network Toronto,
`
`Sciopsis inc Evidence Based NutrL1Mcdicinc, Richmond Hill, Ontario, CANADA
`
`Journal oflhe American College oi'Nulrition, Vol. 26, No. 1, 39-48 (2007)
`Published by the American College of Nutrition
`
`Page 1
`
`NEPN Ex. 2057
`
`Aker v. Neptune
`IPR2014-00003
`
`

`
`Original Research
`
`Evaluation of the Effect of Neptune Krill Oil on Chronic
`Inflammation and Arthritic Symptoms
`
`Luisa Deutscli,
`
`MD, MSc
`
`Department ofBehm'iorr1I .S'('ic11(.'c and Health Rcscarrli. University Health Network Toronto. Sr'iap.sis l1l('. Evidcnrc Based
`NuImi'lIedm'ne,
`Rrchnrorzd Hill, Umano, (.'ANAI)A
`
`Key words: C-reactive protein, inflanimation, omega-3, phospholipirls, Neptune Krill Oil. NKOT”, antioxidants
`
`Objectives: at To evaluate the effect of Neptune Krill Oil (NK()TMl on (‘-reactive protein (CRP) on patients
`with chronic inflamnration and bl to evaluate the eft'ectivene.ss of NKOW on arthritic symptoms.
`Methods: Randomized. double blind. placebo controlled study. Ninety patients were rccruitctl with con-
`firmed diagnosis of cardiovascular disease and/or rheumatoid arthritis and/or osteoarthritis and with increased
`lcvcls of CRP t_> l .0 mgldl) upon [hrcc consecutive Wcckly blood analysis. Group A rcccivrd NKOW (300 mg
`daily) and Group B received a placebo. CRP and \Vestc1n Ontario and McMaster Universities (\\’OMAC’l
`osteoarthritis score were measured at baseline and days 7, I4 and 30.
`Results: After 7 days of treatment NKOT“ reduced CRP by 19.3% compared to an increase by lS.7‘.‘"o
`observed in the placebo group (p = 0.0491. After 14 and 30 days of treatment NKOT“ further dccrcascd CRP
`by 29.7% and 30.9% respectively (p <. 0.00! I. The CRP levels of the placebo group increased to 32.l% after
`14 days and their decreased to 25.1% at day 30. The between group difference was statistically significant; p =
`0.004 at day l4 and p — 0.008 at day 30. NKOW showed a significant reduction in all three WOMAC scores.
`After 7 days of treatment NKUT“, reduced pain scores by 28.9% (p = 0.0501, reduced stiffness by 20.3% (p =
`0.001] and reduced functional impaimtent by 22.8% (p = 04008).
`Conclus’on: The results of the present study clearly indicate that NKOW at a daily dose of 300 mg
`significantly inhibits inflammation and reduces arthritic symptoms within a short treatment period of 7 and I4
`days.
`
`INTRODUCTION
`
`Inflammation is closely linked to the pathogenesis of ath-
`erosclerosis and joint disease and may be provoked by nonin-
`fectious (c.g.,
`injury. smoking, diabetes, obesity) as well as
`infectious sources. C—reactive protein (CRP), which is one of
`the most useful biomarkcrs of inflammation, appears to be a
`central player in the hannful effects of systemic inflammation
`and an easy and inexpensive screening test to assess inflam-
`mation-associatcd risk [1]. Unlike other markers of inflamma-
`tion, CRP levels are stable over long periods, have no diurnal
`variation and can be measured inexpensively.
`Current studies suggest that CRP is a strong predictor of
`future cardiovascular events [C‘.—5]. At all levels of estimated
`l0-year risk for events according to the Framingham risk score
`and at all levels of LDL cholesterol, CRP remained a strong
`
`predictor of future cardiovascular risk [6]. CRP has been shown
`in several prospective, nested case-control studies to be asso-
`ciated with an increased risk of myocardial infarction [7—l2],
`stroke [73,] 3.14], sudden death from cardiac causes [I5], and
`peripheral arterial disease [16].
`In arthritic joints CRP production reflects the release of
`proinflarnmatory cytokrncs, such as intcrlcukms-l and -6 (IL-l
`and IL-6) and tumor necrosis factor-alpha (TNF-oi). which are
`essential in the mechanism of cartilage degeneration [17—22].
`CRP is significantly increased in patients with rheumatoid
`arthritis and slightly but significantly higher in patients with
`osteoarthritis than in matched controls [1,23—29J. CRP was also
`found to increase in patients with knee osteoarthritis showing
`disease progression as well as in patients with rapidly destructive
`hip osteoarthritis [24-29]. Contrary to erythrocyte sedimentation
`rate (ESR). evidence has provcn a strong association between CRP
`
`Address reprint requests to: Dr. Luisa Deuisclr. Sciopsis lnc. F.vi<lence Based NutraMedicine. I8 Corso Court, Richmond llill_ Ontario l,-SS lll4. C-\NAl)A. F.-marl:
`lt.L~t;iop.~is @' yahr I(l.l."d
`
`Journal of the American College of Nutrition, Vol. 26, No. 1, 39-48 (2007)
`Publishcd by the American College of Nutrition
`
`Page 2
`
`

`
`Eflerl of Neptune Krill Oil
`
`and level of clinical severity in patients with osteoarthritis of the
`knee or hip [24,26].
`The results of human studies on the anti-inflammatory
`properties of omega-6 and omega-3 fatty acids are contro-
`versial, varying from no effect to a beneficial effect [30—34].
`A proposed competition between omega-3 and omega-6
`fatty acids may be the reason for the observed discrepancies
`of the effects of n—3 fatty acids on cytoltines [35]. Both
`omega-3 and omega-6 fatty acids are substrates for the
`production of human eicosztnoids and share the same en-
`zymes for the synthesis of prostaglandins and leukotrienes.
`Omega-3 fatty acids produce eicosanoids with fewer inflam-
`matory properties than those derived from omega-6 fatty
`acids [36-38]. Hence, a dominant ratio of dietary intake of
`omega-3 versus omega-6 fatty acids is critical to inflamma-
`tory processes.
`
`Neptune Krill Oil is extracted from Antarctic Krill (Epitaxi-
`sin Superba), a zooplankton at the bottom of the food chain.
`Even though krill is the main food source for whales it remains
`the most abundant biomass on earth because of its high regen-
`eration properties. The krill used for Neptune Krill Oil
`is
`harvested in the Antarctic Ocean where the worldwide harvest
`
`is less than 0.1% the allowed fishing quota. Being at the bottom
`of the food chain, having a very short lifespan of l—’.’. years and
`living in the clean waters of the Antarctic Ocean, makes the
`krill and thus Neptune Krill Oil naturally pure of heavy metals,
`dioxins and pesticides.
`The oil is extracted by a patented cold vactulrn extraction
`process that protects the biomass from exposure to heat. light or
`oxygen. This protects the oil
`through-out its production and
`maintains the original nuuients of krill intact. The result is a
`concentrate of novel marine phosplrolipid carriers of eicosa-
`pcntemoic (EPA) and docosahexanoic (DHA) fatty acids and
`potent antioxidants. The main antioxidants, astaxanthin and a
`novel flavonoid, similar to the 6,8-Di-C‘.-glucosylluteolin, es-
`terify the EPA and DHA respectively. This provides a signif-
`icant stability and antioxidant potency to the oil.
`Anecdotal data suggests that Neptune Krill Oil may be
`effective for the management of arthritic symptoms. Evidence
`has shown that phospholipids, omega-3 fatty acids and astax-
`anthiu have direct or indirect anti-ittflamnratory properties
`[9—l3.30—53]. Phospholipids protect the cell membrane for
`toxic injury [39]. Multiple studies have proven EPA and DHA
`to trigger secretion of anti—inflammatory prostaglandins of
`the 3 series (PE3, P13 and thromboxane A3) and interleukin-6
`resulting in a decrease CRP and tumor necrosis factor (TNF)
`[30—38,40—53]. Astaxanthin inhibits
`the production of
`proinflammalory prostaglandins tPGE2‘I and TNF [9—l 3.4]-
`43]. A dietary supplement that contains a natural combina-
`tion of phospholipids. EPA, DHA and astaxanthin may offer
`an alternative regimen for the management of chronic in-
`flammatory conditions.
`
`Considering the continuously increasing evidence of ad-
`verse events related to the chronic use of non-steroidal anti-
`
`inflamrnatory drugs (NSAIDs). which represent the gold starr-
`dard for the treatment of chronic inflammatory conditions. it is
`imperative to research for more innovative and safer treatments
`[54—bl]. The current study addresses the need for safer alter-
`natives in the management of inflammation and arthritic dis-
`ease and evaluates the hypotheses that Neptune Krill Oil is safe
`and effective for the reduction of inflammation as measured by
`serum CRP and the management of pain in patients with
`arthritic disease. The objectives of the present study were a) to
`evaluate the effect of NKOTM on CRP in patients with chronic
`inflammation and h) to evaluate the effect of NKOW on the
`quality of life of patients with arthritic disease.
`
`MATERIALS AND METHODS
`
`Patients
`
`Adult patients between 30 and 75 years with a confirmed
`diagnosis of cardiovascular disease and/or rheumatoid arthritis
`and/or osteoarthritis and with increased CRP levels at l.0 rug/dl
`or more and a standard deviation not higher than 0.05 in three
`consecutive weekly tests, who fulfilled the inclusion criteria
`and signed an informed consent form, were included in the
`study. Excluded from the study were patients who could not
`restrain from consuming alcohol for the duration of the study,
`with a history of gastrointestinal perforation or hemorrhage or
`symptomatic peptic ulcer. Patients with seafood allergy, diabe-
`tes or concurrent medical disease or concomitant treatments
`
`(including postmenopausal hormones) that could confound or
`interfere with the outcome measures. as well as those taking
`concomitzmt anticoagulants were not eligible for enrollment.
`Also excluded were patients with moderate or severe depres-
`sion or who were unable to respond to the study questionnaire.
`Women of childbearing age were required to have confirmed
`use of adequate contraception since their last menses and to
`agree to continue this practice during the study.
`
`Study Design
`
`In this prospective randomized double blind clinical trial 90
`patients who fulfilled the study criteria were recruited from the
`practices of primary care physicians in Ontario, Canada. Pa-
`tients were randomly assigned by a computer-generated sched-
`ule into one of two groups. The first group (Group A) received
`NKOW at a daily moming dose of 300 mg; the second group
`(Group B) received a neutral placebo. The NKO“‘ contained
`17% EPA, 10% DHA and an omega-3 versus omega-6 ratio of
`15 to l. The placebo used was microcrystalline cellulose. Both
`the NKOT“ and the placebo were administered in non-distin-
`guishable glycerirr softgels. Compliance was tested by a count
`of softgels at each visit after 7, 14 and 30 days. All blood tests
`were taken at a central lab in the morning. between 7:00 and
`
`40
`
`VOL. 26. NO.
`
`1
`
`Page 3
`
`

`
`10:00 am under fasting conditions for 8 hours. Blood sampling
`and testing occurred weekly during the 3 week screening pe-
`riod, at baseline after the 1 week wash-out and at each fol-
`
`low-up visit after 7. 14 and 30 days of treatment.
`Patients were asked to stop use of all dietary supplements.
`especially those containing omega-6, foods containing a high
`content of omega-6 (corn, soy, safflower and sunflower oils
`and sunflower seeds) and all analgesics (except acetamino-
`phen) and anti-inflammatory medications for two weeks prior
`to initiation of the trial for washout purposes. Patients were
`allowed to take acetaminophen (650 mg caplets) as a rescue
`analgesic medication. for severe pain throughout the trial. The
`maximum dose of acetaminophen allowed was as recom-
`mended by the manufacturer; 1-2 capsules every 8 hours. All
`patients were instructed to keep a diary of their acetaminophen
`consumption and report it at their next scheduled visit.
`Ninety patients were recruited. 45 per group, of whom 44
`patients in the NKOW group and 43 patients in the placebo
`group completed 30 days of treatment. Two patients withdrew
`from the study, one per group, after a minor accident
`that
`required additional analgesic treatment. One patient on placebo
`withdrew for personal reasons. The mean age of patients in the
`NKOT” group was 54.6 (14.8) years and 55.3 (14.3) years in
`the placebo group. There were 25 (55.6%) male patients in the
`NKOT“ group and 22 (48.9%) in the placebo group.
`In Group A and B respectively, 5 and 7 patients were
`diagnosed only with atherosclerosis, 18 and 16 patients only
`with osteoarthritis, 10 and 12 patients only with rheumatoid
`arthritis and I2 and 10 patients with cardiovascular disease and
`osteoarthritis. Overall, in the NKOW and placebo group re-
`spectively. l7 and 17 patients were diagnosed with cardiovas-
`cular disease, 30 and 26 with osteoarthritis and 10 and 12 with
`rheumatoid arthritis.
`
`Outcome Measures
`
`During the screening period, in order to an oid the inclusion
`of patients with acute inflammation, the primary efficacy pa-
`rameter, C-reactive protein, was measured weekly for three
`consecutive weeks. Patients who maintained :1 CRP of at least
`
`1 mg/dl, without fluctuations higher than 0.05 mg, were blindly
`randomized in their group and after the washout period initiated
`their respective treatment, either NKOTM or placebo. CRP was
`further tested after 7, 14 and 30 days of treatment.
`At baseline as well as at each of the three follow-up visits.
`patients with arthritic disease were asked to complete the
`Western Ontario and McMaster Universities (WOMAC) ar-
`thritic pain asscssmcnt questionnaire. The Western Ontario and
`McMaster (WOMAC) University osteoarthritis score is a 24-
`item questionnaire completed by the patient and focusing on
`joint pain, stiffness and loss of function related to osteoarthritis
`of the knee and hip [62—77]. The WOMAC is used extensively
`in clinical trials for the evaluation of the effect of investiga-
`tional products on the treatment of osteoarthritis. Even though
`
`Eflert of Neptune Krill Oil
`
`it was initially developed for the assessment of pain, stiffness
`and function of daily living in the elderly with osteoarthritis it
`has recently been revised for younger and./or more active pa-
`tients with knee injury and/or knee or hip osteoarthritis. It
`provides a validated assessment of the patient's functional
`capacity. specifically joint pain, stiffness and functional impair-
`ment [62—77]. The WOMAC osteoarthritis score has 3 sub-
`scales with 24 items: 5 items assessing pain. 2 items for
`stiffness. and 17 items measuring physical function. It can be
`self-administered in less than 5 minutes. The WOMAC can be
`
`both scored separately for each subscale and together to give a
`composite score. The scale employed in this study to quantify
`patient global assessment of disease activity was the Likert
`scale; a 5-point scale in which 0 represents the best outcome
`and 4 the worst. Minimal clinically significant change is con-
`sidered a decrease of 0.4 mm on each item in the three sub-
`
`scales [7I—77]. In order to avoid environmental or other bias,
`all patients responded to the WOMAC in the physician’s office
`before their examination.
`
`Statistical Design
`
`A sample size of 90 patients (45 patients per group) pro-
`vided 80% power to detect a CRP reduction of 10% from
`baseline to 14 days. Within group differences reflecting
`changes over time for the same patient were assessed for
`statistical significance with the Paired Studcnt’s t-test. Between
`group differences were assessed with planned comparisons of
`one way analysis of variance. Statistical significance was set at
`p < 0.05. Values are presented as mean i standard deviation.
`
`RESULTS
`
`At baseline, there was no significant difference between
`groups with regards to concomitant medications (p — 0.987).
`CRP levels ([2 = 0.087) and the three WOMAC scores (pain -
`p = 0.539. stiffness — p = 0.104, functional impairment - p =
`0.105). Patients on NKOT“ reduced their consumption of res-
`cue medieations between baseline and 30 days by 31.6% and
`significantly less consumption than patients on placebo, who
`reduced their acetaminophen intake by 5.9% (p = 0.012).
`After 7 days of treatment NKOT“ reduced mean (SD) CRP
`by 19.3% (1.1) compared to an increase by 15.7% (1.9) ob-
`served in the placebo group. The difference between the two
`groups was statistically significant (p = 0.049). NKOT“ further
`decreased CRP after 14 and 30 days of treatment by 29.7%
`(0.9) and 30.9% (l.0_) respectively. The CRP levels of the
`placebo group increased by 32.1% (1.9) after 14 days and then
`decreased to 25.1% (I .l) at day 30. The within group decrease
`of mean (SD) CRP by NKO“-‘ through the three testing periods
`was statistically significant (p = 0.001). Contrary the CRP in
`the within placebo group increased significantly (p = 0.028).
`The between group difference in all three testing days was
`
`JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
`
`41
`
`Page 4
`
`

`
`Eflert of Neptune Krill Oil
`
`Table 1. C-Reactive Protein (CR?) mg/dl by Group and Visit
`
`Visit
`
`Baseline
`
`7 Days
`
`I4 Days
`
`30 Days
`
`Mean
`Std Deviation
`Median
`Mean
`
`% Change (Bascline—7 days)
`Std Deviation
`Median
`Mm“
`% (‘I-range (‘Baseline—l4 days!
`Std Deviation
`Median
`Mean
`96 Change (Basclinc~30 days)
`Std Deviation
`Median
`
`P-value (Within Groups iullnteraction
`
`Table 2. WOMAC Pain Scoies by Group and Visit*
`
`Baseline
`
`7 Days
`
`Mean
`Std De\-‘iation
`Median
`Mean
`Std Deviation
`Median
`Mean
`Std Deviation
`Median
`Mean
`Std Deviation
`Median
`P value (Within Groups}/Interaction
`* 0 represents the best outcome and 4 the worst.
`
`Visit
`
`14 Days
`
`30 Days
`
`Placebo
`2.87
`
`L25
`2.83
`3.32
`
`15.7
`1.92
`3.26
`3.79
`
`32.1
`1.88
`4.02
`3.59
`
`L05
`3.44
`0.028
`
`NKUW
`300 mg/day
`2.49
`
`L85
`2.28
`2.01
`
`- 19.3
`1.08
`I .95
`l.75
`
`— 29.7
`0.88
`1.86
`1.72
`
`l.0
`L69
`0.00!
`
`Gm“?
`
`(1:30
`3.39
`
`.91
`3. I 9
`2.4!
`
`.90
`2.19
`2.52
`
`.79
`2.39
`2.04)
`
`.85
`2.02
`0.002
`
`Placebo
`3.07
`
`.60
`3.00
`2.78
`
`.61
`2.71
`3.26
`
`.67
`3.21
`3.05
`
`.59
`3.00
`0.138
`
`P value
`b
`
`0087
`
`0049
`
`0.004
`
`P value
`(Between
`Groups)
`
`0539
`
`0052
`
`0003
`
`0009
`
`statistically significant; p - 0.049 at 7 days, p — 0.004 at day
`14 and p = 0.008 at day 30 tTable 1).
`Tables 2-7 present
`the effects of NKOT” on the 3
`WOMAC osteoarthritis scores compared to placebo, from
`baseline to 30 days. NKOW showed a significant reduction
`in all
`three WOMAC scores. NKOT“ reduced pain signifi-
`cantly more than placebo in all three follow-up visits: p =
`0.()50 at visit 1 (day 7), p = 0.049 at visit 2 (day 14) andp =
`0.011 at visit 7» (day 7:0) Similar effects were observed with
`the stiffness and functional impairment scores. In all three
`follow—up visits the between group differences in change of
`stiffness (p = 0.001) and functional impairment (p = 0.005)
`were statistically significant
`(Tables 4-7). No adverse
`events were reported during the 30 days of treatment with
`Neptune Krill Oil.
`
`DISCUSSION
`
`Non-steroidal anti-inflammatory agents (NSAIDS) are the
`most commonly prescribed agents for inflammatory conditions.
`NSAIDS are drugs with analgesic, antipyretic and anti-inf|am-
`matory effects. Most NSAIDs, such as aspirin, ibuprofen and
`naproxen act as non-selective inhibitors of cyclnoxyge.nase—
`they inhibit both the cycl0oxygenase—l (COX-1) and cyclo0x-
`ygenase-2 (COX-2) isnenzymes, whereas COX-2 inhibitors
`selectively inhibit the cyclooxygenase—2 isoenzyme. The main
`advantage of NSAIDS is that, unlike opioids,
`they do not
`produce sedation, respiratory depression, or addiction. Certain
`NSAIDS have become accepted as relatively safe, resulting in
`the rescheduling of these agents, e.g. ibuprofen, to allow avail-
`ability over-the-counter. However, recent evidence suggests an
`
`Page 5
`
`VOL. 26. NO.
`
`1
`
`

`
`Table 3. Change in WOMAC Pain Scores! 100 by Group and Visit‘
`
`Eflert of Neptune Krill Oil
`
`Visit
`
`7 Days
`
`14 Days
`
`30 Days
`
`Mean
`
`Std Deviation
`Median
`P-Value (Visit)
`Mean
`Std Deviation
`Median
`P—Va|iie lVisitl
`Mean
`Std Deviation
`Median
`P-Value (Visit)
`
`" (J represents the best outcome and 4 the worst.
`
`Table 4. WOMAC Stiffness Scores by Group and Visit‘
`
`Baseline
`
`7 Days
`
`Mean
`Std Deviation
`Median
`Mean
`Std Deviation
`Median
`Mean
`Std Deviation
`Median
`Mean
`Std Deviation
`Median
`P value (Within Groups l/Interaction
`“ ll represents the best outcome and 4 the worst.
`
`Visit
`
`14 Days
`
`30 Days
`
`Group
`
`-0
`N13:gl(1:30
`-2891
`
`is.7n
`-25.00
`0.001
`-25.66
`
`l5.27
`—?_i_0t'l
`0,022
`-38.35
`
`-30.00
`0.001
`
`Group
`
`3
`Nfigdago
`3.45
`
`.95
`3 48
`...75
`
`.84
`_ 43
`2.55
`.79
`2.50
`2.10
`
`.85
`2.00
`0.002
`
`Placebo
`-9.44
`
`26.98
`-10.00
`0.290
`6.18
`
`13.54
`.00
`0.208
`-0.6
`
`.00
`0.610
`
`Placebo
`2.85
`
`.85
`3.02
`3.35
`
`.53
`3.10
`2.83
`.99
`3.00
`2.97
`
`.72
`3.01
`0.324
`
`P value
`
`(Between
`Groups]
`
`0050
`
`0019
`
`P value
`
`(‘Between
`Gmups)
`
`0. I 04
`
`0030
`
`0.056
`
`0043
`
`association between COX-2 inhibitor exposure and cardiovas-
`cular risk. Considering that small increases in ambulatory and
`clinic systolic blood pressure in patients with hypertension and
`type 11 diabetes are associated with substantial increases in the
`risk of cardiovziscular morbidity, the use of these medications
`has been restricted to the lowest effective dose for the shortest
`
`possible duration of treatment [54—6l].
`Neptune Krill Oil is a rich source or unique phospholipid
`carriers of nmeg:i—3 fatty acids, eicosapentanoic acid (EPA) and
`docosahexanoic acid (DHA), esterified on antioxidants, as
`astaxaiithin and a novel flavonoid. Phospholipids are important
`in protecting membranes from toxic injury and free radical
`attack [39]. The. composition of phospholipids in Neptune Krill
`Oil appears to be optimal to offer such protection. The unrav-
`eling of the exact mechanism of action is a multifactnrial
`project which is still ongoing. We speculate that it is based on
`the blockage of leukotriene formation by interfering at the level
`
`of the lipoxygcnasc pathways. The significantly dominant ome-
`ga-3 to omega-6 ratio (1521) in Neptune Krill Oil may partially
`explain the anti-inflaminatory effects observed in this trial. The
`balance or polyuiisaturated (essential) fatty acids in the body is
`critical for the maintenance of healthy cell membranes and
`hormone regulation. During the last decades. the American diet
`has shifted to much higher levels of omega-6 and less omega-3
`fatty acid intake. Lon g-chain omega-o such as arachidonic acid,
`predominating in the phospholipids of cell membranes can
`encourage the production of pro—infl2tmmatoi'y type-2 prosta-
`glandins (PGE2), while omega-3 fatty acids promote the pro-
`duction of anti-inflammatory prostaglandins [1,2]. An addi-
`tional factor is the. naturally occumng zistaitanthin in NKOTM
`which may also actively contribute in its anti-inflammatory
`potency. A recent study by Ohgami K. et al demonstrates that
`astaxanthiii inhibits nitric oxide production through inhibiting
`the activity of inducible nitric oxide synthase (NOS), and
`
`JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
`
`43
`
`Page 6
`
`

`
`Eflert of Neptune Krill Oil
`
`Table 5. Change in WOMAC Stiffness Scores/100 by Group and Visit"‘
`
`Vim
`
`7 Days
`
`14 Days
`
`39 Days
`
`" (J represents the best outcome and 4 the worst.
`
`Mean
`
`Std Deviation
`Median
`P-Value (Visit)
`
`Mean
`Std Deviation
`Median
`P-Value (Visit)
`Mean
`
`Std Deviation
`Median
`P-Value (Visit)
`
`Table 6. WOMAC Functional Impairment Scores by Group and Visit“
`
`4
`,
`V5“
`
`Baseline
`
`7 Da
`
`Y5
`
`H Days
`
`Mean
`
`Std Deviation
`Median
`Mean
`Std Deviation
`Median
`Mean
`
`Std 1')e\‘1at1on
`Median
`Mean
`
`Std Deviation
`30 Days
`Median
`P value (Wid1in Gmupst/Interaction
`“ 0 represents the best outcome and 4 the Worst.
`
`Group
`
`NKO 300
`mglday
`-20.29
`
`24.3!
`-25.00
`0.004
`
`- 26.09
`27.05
`-3135
`0002
`-39.13
`
`27.67
`-31.25
`0.003
`
`Group
`
`NKO 300
`
`mg/day
`3.34
`
`9|
`3.41
`2.58
`.58
`2.3:
`2.36
`
`.31
`2.56
`3.14
`
`.68
`2.66
`0.018
`
`Table 7. Change 111 WOMAC Functional Impairment Scores/100 by Group and Visit*
`
`Visit
`
`7 Days
`
`I4 Days
`
`30 Days
`
`" 0 represents the best outcome and 4 the worst.
`
`Mean
`Std Deviation
`Median
`P-Value (Visit)
`Mean
`Std Deviation
`Median
`P—Value (Visit)
`Mean
`Std Deviation
`Median
`P-Value (Visit)
`
`Group
`
`NKO 300
`mglday
`— 22.75
`10.59
`- 2.53
`0.005
`- 29.34
`14.07
`- 14.02
`0.016
`— 35 .93
`9.69
`- 20.47
`0.08
`
`Pl acebo
`
`-17.54
`29.88
`25.00
`0.127
`-0.70
`20.55
`L00
`0.820
`4.2!
`26.74
`12.50
`0.879
`
`2.63
`1.78
`
`2.9|
`0.138
`
`Placebo
`
`-1.34
`5.86
`1.55
`0.750
`-11.07
`13.06
`-0.15
`11.094
`-5.71
`7.34
`-3.1 I
`0.269
`
`P value
`(Between
`Groups}
`
`0.001
`
`0.018
`
`0 023
`
`P value
`(Between
`Groups)
`
`0.105
`
`0.023
`
`0.021
`
`0.135
`
`P value
`t Between
`Groups)
`
`0 008
`
`0.040
`
`0.005
`
`44
`
`VOL. 26. NO.
`
`1
`
`Page 7
`
`

`
`production of PGE2 and TNF-. This study suggests that astax—
`anthin may have an anti-inflammatory effect and may be a
`promising agent for the treatment of inflammation [43].
`The present study confirms the results of previous research
`demonstrating the anti—inflarnmatory effects of EPA and DHA and
`of a dominant omega-3 versus omega-6 ratio [30—38,40,44 -53].
`Simopoulos has shown that omega-3 fatty acids lower CRP more
`so than arty other nutrient, which accounts for decreasing the risk
`for coronary heart disease [45]. Human and animal studies have
`provided evidence that dietary intake of omega-3 fatty acids mod-
`ifies inflammatory and immune reactions. This makes making
`omega-3 fatty acids potential therapeutic agents for inflammatory
`diseases [30—38.40,4-1-53].
`A possible explanation for the increase of CRP observed in
`the placebo group is the interruption of all anti-inflammatory
`regimens one week prior and for the duration of the trial. Since
`the patients enrolled suffered from a chronic inflammatory
`condition with chronically high CRP, the cessation of all anti-
`inflannnatory treatment may have triggered the increased pro-
`duction of CRP.
`
`The significant reduction of pain shown in the WOMAC
`pain score is also demonstrated the significantly lower con-
`sumption of NSAIDs by the group of patients treated with
`NKOT“. This finding becomes even more significant
`if we
`consider the nephrotoxicity of NSAIDs mainly among patients
`with chronic inflammatory diseases.
`The results of the present study validate the potent anti-
`inflainmatory properties of NKOT“ and reinforce the potential
`mechanism of action. The CRP reduction induced by NKOT“
`demonstrates that NKO"“ is 21 safe and effective alternative for
`
`the treatment of inflammation, particularly with all the recently
`proven adverse events of the most widely used NSAIDS. Fur-
`thermore, this study demonstrates a significant improvement in
`all 3 WOMAC scores among the 30 and I0 patients on NKOT“
`as compared to the 26 and 12 patients on placebo who were
`diagnosed with osteoarthritis and rheumatoid arthritis. No ad-
`verse events were reported making NKOW safe for human
`consumption.
`
`CONCLUSION
`
`The rcsults of the present study indicate that NKO” at a
`daily dose of 300 mg may within a short time to reaction (7-14
`days) significantly inhibit inflammation by reducing CRP as
`well as significantly alleviate symptoms caused by osteoarthri-
`tis and rheumatoid arthritis. Further research is required to
`better understand the mechzmism of action and to compare the
`effects of NKO with other anti-inflammatory agents prcscntly
`used as standard care.
`
`Eflert of Neptune Krill Oil
`
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