CX-0264
`CX Page
`
`Evaluation of the Effects of Neptune Krill Oil
`
`on the Clinical Course of Hyperlipidemia
`
`Roxandra Bunea M.D Khassan El Farrah M.D M.Sc.2
`Luisa Deutsch M.D M.Sc.2
`
`of Internal Medicine McGill University Riverview
`Assistant Professor Department
`Medical Center Montreal Quebec Canada
`
`JSS Medical Research Montreal Quebec Canada
`
`Altern Med Rev 2004
`
`420-428
`
`EP877ITC-00040885
`
`NEPN Ex. 2056
`Aker v. Neptune
`IPR2014-00003
`
`Page 1
`
`

`
`CX Page
`
`Evaluation of the Effects of
`Neptune KrillOil on the Clinical Course
`of Hyperlipidemia
`
`Ruxandra Bunea 1ID Khassan El Farrah MD MSc
`Luisa Deutsch MD
`
`Abstract
`OBJECTIVE To assess the effects
`
`of
`
`krill
`
`oil
`
`triglycerides
`
`on blood lipids specifically
`total cholesterol
`low-density lipoprotein LDL and
`high-density lipoprotein HDL METHODS
`three-month prospective
`multi-center
`randomized study followed by
`three-month
`controlled follow-up of patients treated with
`and 1.5
`oil daily Patients with
`
`krill
`
`hyperlipidemia able to maintain
`healthy diet
`and with blood cholesterol
`levels between 194
`
`in
`
`daily
`
`for
`
`results of the present study demonstrate within
`high levels of confidence that krill oil is effective
`the management
`by
`of hyperlipidemia
`total cholesterol LDL
`reducing
`significantly
`and triglycerides and increasing HDL levels
`At
`lower and equal doses krill
`oil was
`significantly more effective
`than fish oil for the
`of glucose triglycerides and LDL
`reduction
`
`levels
`
`Altern Med Rev 2004
`
`Introduction
`
`for the
`
`The balance of polyunsaturated essential
`fatty acids PUFAs in the body is critical
`cell membranes and hor
`maintenance
`of healthy
`few decades the
`mone regulation During the last
`fatty acid content of the U.S diet has shifled so it
`flow contains much higher levels of omega-6 and
`less omega-3 fatty acids When long-chain
`fatty acids predominate in the phospholipids of
`cell membranes the production of pro-inflamma
`tory type-2 prostaglandins PGs and
`leukotrienes LTs are encouraged
`whereas the
`presence of omega-3 fatty acids promotes
`the pro
`duction of anti-inflammatory POs and LTs.2
`
`omega-
`
`type-4
`
`Bunea MD
`Ruxandra
`Assistant
`Internal Medicine McGill University
`Center Montreal Quebec Canada
`address
`1586 Ave des Pins
`Correspondence
`H3G B4
`Montreal Quebec Canada
`
`Professor
`
`Riverview
`
`Department of
`Medical
`
`302
`
`El Farrah MD MSc
`Khassan
`Montreal Quebec Canada
`
`JSS Medical
`
`Research
`
`MD
`Luisa Deutsch
`Quebec Canada
`
`JSS Medical
`
`Research
`
`Montreal
`
`and 348 mg/dL were eligible for enrollment
`sample size of 120 patients 30
`the trial
`was randomly assigned to one
`patients/group
`received krill oil at
`of four groups Group
`body mass index BMI-dependent
`were
`dosage of 2-3 daily Patients in Group
`krill oil daily and Group
`was
`180 mg
`containing
`acid EPA and 120 mg
`eicosapentaenoic
`docosahexaenoic acid DHA per gram of oil
`dose of
`was given
`daily Group
`containing microcrystalline cellulose
`placebo
`The krill oil used in this study was Neptune Krill
`Oil NKO provided by Neptune Technologies
`Laval Quebec Canada
`Bioresources
`OUTCOME MEASURES Primary parameters
`and 90-day visit were total
`tested baseline
`LDL HDL and
`blood cholesterol
`Krill oil 1-3 g/day BMI
`glucose RESULTS
`to be effective
`dependent was found
`for the
`reduction of glucose total cholesterol
`triglycerides LDL and HDL compared to both
`fish oil and placebo CONCLUSIONS The
`
`given 1-1.5
`
`fish
`
`oil
`
`given
`
`at
`
`triglycerides
`
`Page 420
`
`Alternative Medicine Review
`
`Volume
`
`Number
`
`2004
`
`Copyright2004 Thorne Research
`
`Inc All Rights Reserved No Reprint Without Written Perniission
`
`EP877ITC-00040886
`
`Page 2
`
`

`
`CX Page
`
`oniega-3
`
`fatty acids highly facilitates
`
`the passage
`
`of fatty acid molecules through the intestinal wall
`and ultimately improv
`
`bioavailability
`
`increasing
`
`ing the omega-3omega-6 fatty acid ratio.89
`
`Materials and Methods
`
`12-week double-blind randomized
`to high EPA
`trial was conducted comparing krill oil
`and DHA 32 ratio fish oil and placebo Eligible
`patients were 18-85 years and had at
`month diagnosis of mildly high to very high blood
`193.9-347.9 mg/dL and triglyceride
`cholesterol
`levels 203.8-354.4 mg/dL Patients with famil
`ial hypercholesterolemia severely high cholesterol
`349 mg/dL pregnancy
`known
`or suspected
`known alcohol or drug
`allergy to fish or seafood
`known
`
`abuse within
`
`the
`
`previous
`
`year
`
`least
`
`six-
`
`coagulopathy or receiving
`therapy
`anticoagulant
`or co-morbidity that would interfere with study
`results were excluded
`from the study
`
`Enrolled patients were randomly assigned
`to one of four groups
`Krill oil 2-3
`once daily
`Group
`Body Mass Index BMI
`BMI 30
`g/day
`
`g/day
`
`30
`
`Krill oil 1-1.5
`
`Group
`BMI
`30
`g/day
`BMI30 1.5 g/day
`Follow-up 500 mg/day for 90 days
`
`once daily
`
`Fish oil 32 containing
`Group
`EPA and 120 mg DHA per gram
`once daily
`
`180mg
`
`Group
`
`placebo
`
`once daily
`
`Patients were allowed to continue
`
`lipid-
`
`lowering medications at
`asked to report
`
`any
`
`change
`
`the usual daily dose and
`in dosage Natural
`two-week
`
`were discontinued
`health products
`washout
`period prior to study initiation and there
`after for the study duration Patients were asked
`to record concomitant medications taken daily
`
`for
`
`Omega-6 fatty acids mainly arachidonic
`an inflamma
`shown to initiate
`been
`acid have
`
`eicosapentaenoic
`
`species
`
`omega-3
`
`cular disease
`
`disorders
`
`suggests
`
`cellular
`
`neous
`
`in the
`
`flux of inflammatory
`by triggering
`tory process
`PGs
`and LTs.34 Omega-3 fatty acids mainly
`acid EPA and docosahexaenoic
`acid DHA compete with the omega-6
`for the enzyme prostaglandin
`synthetase Omega-
`fatty acids trigger secretion of less potent 5-se
`and anti-inflammatory PGs of the
`ries LTs
`se
`thromboxanes-A3.4-9 Conse
`and
`ries PE3 PT3
`quently supplementation with EPA and DHA pro
`motes the production of less potent PGs and LTs
`in the formation of inflam
`resulting in decrease
`matory mediators.-3
`The exact mechanism of action by which
`fatty acids favorably modify cardiovas
`and associated
`is not yet
`Evidcncc
`an increased
`fully confirmcd
`intake of EPA and DHA results in an increase of
`EPA and DHA in tissue
`lipids and circu
`In parallel
`they result in simulta
`latory lipids.14
`reduction of omega-6 fatty acids
`body.4 This fatty acid shift
`is predominantly
`marked in cell membrane-bound phospholipids
`and results in alteration of the physicochemical
`of cell membranes
`This favorably
`
`properties
`
`modifies cellular
`
`functions including
`cell signal
`processes and
`
`ing gene expression biosynthetic
`formation.5
`Human studies have
`revealed the ability
`of EPA and DIIA to significantly
`reduce circulat
`ing levels of blood triglyceride and very low-den
`sity lipoprotein VLDL which have
`been asso
`ciated with increased
`risk of cardiovascular
`
`eicosanoid
`
`dis
`
`ease 1617
`
`Krill oil
`
`is extracted
`
`from Antarctic krill
`
`Euphausia
`
`superba
`
`zooplankton crustacean
`
`rich
`
`carrying
`
`in phospholipids
`omega-3
`long-chain
`PUFAs mainly EPA and DHA Krill oil also con
`vita
`
`tains various
`
`mins
`
`and
`
`potent antioxidants
`astaxanthin and
`
`including
`
`novel
`
`flavonoid
`
`but with two
`
`similar to 68-di-c-glucosylluteolin
`or more glucose molecules and one aglycone
`Krill oil has
`unique biomolecular pro
`file of phospholipids naturally rich in omega-3
`fatty acids and diverse
`
`antioxidants
`
`significantly
`
`different
`
`association
`
`from the usual profile of fish oils The
`between phospholipids
`and long-chain
`
`Alternative Medicine Review
`
`Volume
`
`Number
`
`2004
`
`Page 421
`
`Copyright2004 Thorne Research
`
`Inc All Rights Reserved No Reprint Without Written Permission
`
`EP877ITC-00040887
`
`Page 3
`
`

`
`Table
`
`Results of Krill Oil 1.0 g/day on Lipids
`
`Table
`
`Results of Knit Oil 1.5 g/day on Lipids
`
`CX Page
`
`Statistical
`
`Rationale
`
`and Analysis
`
`sample
`size of 120 pa
`30 pa
`tients
`pro
`tients/group
`vided 90-percent
`
`power to detect
`15-percent
`change in total
`from
`
`cholesterol
`
`baseline
`
`to three
`
`months
`
`Within-
`
`group differences
`reflecting
`changes over time
`for the same pa
`as
`tient were
`
`sessed
`
`for statisti
`
`cal significance
`
`with the Paired
`
`Students t-test
`
`differences
`
`Between-group
`were
`with
`
`assessed
`
`planned compari
`sons of one-way
`of vari
`
`analysis
`ance
`
`Results
`
`One-hun
`dred-twenty patients with mean age of 51
`years
`standard deviation 9.46 and ranging between 25
`in the trial BMI
`and 75 years were enrolled
`indicating weight status in adults was calcu
`tool
`formula
`
`lated according to the metric
`
`in
`
`The primary parameters
`blood glucose cholesterol
`sity lipoprotein LDL and high-density
`tein HDL Fasting blood lipids and glucose were
`as well as 30 and
`90 days
`analyzed at baseline
`
`lipopro
`
`tested were
`low-den
`
`triglycerides
`
`after study initiation
`for the 30 paticnts
`
`for all groups and at
`in Group
`
`days
`
`in cen
`in centimeters
`height
`kilograms/height
`10000.2021 Of the 120 patients en
`tirneters
`rolled 30 25% had moderate-to-severe obesity
`with BMI higher than 30 Sixty-four 53
`sub
`and 26 22% were nor
`jects were overweight
`mal weight with BMI between 25 and 30 and
`lower than 25 respectively Women had
`
`higher
`
`Page 422
`
`Alternative Medicine Review
`
`Volume
`
`Number
`
`2004
`
`Copyright2004 Thorne Research
`
`Inc All Rights Reserved No Reprint Without Written Permission
`
`EP877ITC-00040888
`
`Page 4
`
`

`
`CX Page
`
`Table
`
`Results of Krill Oil 2.0 g/day on Lipids
`
`BMI
`mean
`28.25.1 com
`to men
`pared
`25439 pOOOIi
`Among
`the 60 patients
`the two groups re
`
`in
`
`ceiving krill oil
`
`42 70% had
`BMI of3O or less
`
`In Group
`received
`
`19
`
`patients
`
`krill oil daily
`and the remaining
`11
`received
`
`daily In Group
`were
`23 patients
`
`treated with
`
`daily dose of
`krill oil and with
`
`Table
`
`Results of Krill Oil 3.0 g/day on Lipids
`
`1.5
`
`All patients
`con
`
`in Group
`tinued for an addi
`
`tional
`
`with
`
`90
`days
`mainte
`
`nance
`
`dose of 500
`
`mg krill oil daily
`Baseline
`analysis of demo
`graphic
`
`criteria
`data in
`laboratory
`total cho
`
`cluding
`
`lesterol
`
`and
`
`trig
`
`lyceride levels
`
`ferences
`
`or 1.5
`
`and
`comorbidity
`concomitant
`medication at baseline showed no significant dif
`among the four groups pO 102-0.850
`After 12 weeks of treatment patients
`re
`krill oil daily had
`13.4-per
`ceiving
`decrcase in mean total cho
`cent and 13.7-percent
`from 236 mg/dL and 231 mg/dL to 204
`lesterol
`mg/dL pO.000 and
`199 mg/dL p0.000 re
`The group ofpatients
`and
`krill oil showed
`
`spectively Tables
`
`treated with
`
`or
`
`respective
`
`reduction
`
`significant
`in mean total cholesterol
`
`of
`
`baseline of 247 mg/dL and 251 mg/dL to 203 mg/
`dL pO.000 and
`206 nig/dL pO.000 corre
`and
`In comparison
`
`spondingly Tables
`
`receiving
`
`fish oil had
`
`mean reduction
`from baseline 231
`of 5.9 percent
`tal cholesterol
`mg/dL to 218 mg/dL pO.000 Table
`group showed
`enrolled
`in the placebo
`increase in mean total cholesterol
`cent
`mg/dL to 242 mg/dL pO.000 Table
`
`people
`in to
`
`Those
`
`9.1-per
`
`from 222
`
`18.1 and 18 percent Levels were reduced from
`
`Alternative Medicine Review
`
`Volume
`
`Number
`
`2004
`
`Page 423
`
`Copyright2004 Thorne Research
`
`Inc All Rights Reserved No Reprint Without Written Permission
`
`EP877ITC-00040889
`
`Page 5
`
`

`
`CX Page
`
`4.6% with
`blood levels de
`from 122
`
`creased
`
`mg/dL at baseline
`118 mg/dL
`to
`pO.l4l after
`12
`weeks Patients
`
`placebo
`
`receiving
`showed
`
`nega
`tive effect with
`in
`13-percent
`in LDL
`
`crease
`
`levels from 137
`
`mg/dL to 154 mgI
`dL p0.000
`HDLwas
`in
`significantly
`in all pa
`receiving
`krill oil pO.000
`or
`fish
`oil
`pO.OO2 HDL
`increased
`
`creased
`
`tients
`
`levels
`
`to
`
`krill oil
`
`from 57.2 mg/dL
`82.4 mg/dL
`44% change at
`g/day
`58.8 mg/dL
`to
`83.9 mg/dL 43%
`increase for krill
`
`51
`
`oil 1.5 g/day
`79.3
`mg/dL to
`mg/dL 55% in
`crease at krill oil
`
`and from
`
`to
`
`daily krill oil
`
`increased
`
`Fish oil
`
`g/day
`64.2 mg/dL
`102.5 mg/dL 59% increase at
`dose of
`taken at
`g/day
`HDL from 56.6 mg/dL to 59.03 mg/dL 4.2% in
`crease No significant decrease of HDL pO.8SO
`was observed within the placebo group with lev
`els of HDL remaining almost stable 56.8 mg/dL
`to 56.7 mg/dL
`Krill oil
`
`taken
`
`g/day
`
`reduced
`
`blood
`
`11 percent
`triglycerides by
`non-significant
`120.5 mg/dL to 107.2 mg/dL pO.ll4
`krill oil resulted in non-significant
`dose of 1.5
`
`from
`
`daily
`
`Table
`
`Results of Fish Oil 3.0 g/day on Lipids
`
`Table
`
`Results of Placebo
`
`on Lipids
`
`An analogous
`
`effect
`
`on LDL levels was
`
`observed
`
`creased
`
`in the krill oil
`
`in all groups Krill oil at
`daily dose of
`reduc
`achieved significant
`1.5
`or
`tions of LDL of 32 36 37 and
`39 percent re
`spectively p0.000 Baseline levels were de
`group from 168
`1-g/day
`mg/dL to 114 mg/dL in the
`group from
`.5-g/day
`165 mg/dL to 106 mg/dL and in the 2- and 3-g/
`day groups from 183 mg/dL and
`173 mg/dL to
`The labo
`114 mgldL and 105 mg/dL respectively
`ratory results of patients treated daily with
`oil did not achieve
`reduction
`
`significant
`
`fish
`in LDL
`
`Page 424
`
`Alternative Medicine Review
`
`Volume
`
`Number
`
`2004
`
`Copyright2004 Thorne Research
`
`Inc All Rights Reserved No Reprint Without Written Permission
`
`EP877ITC-00040890
`
`Page 6
`
`

`
`CX Page
`
`11 .9 percent
`reduction
`of
`
`Table
`
`Effect of Lower Maintenance
`
`Dose of Krill Oil on Lipids
`
`triglycerides
`from 122.7 mg/dL
`112 mg/dL
`
`pO 113
`
`to
`
`Subjects
`
`achieved
`
`significant
`
`reduction
`
`of
`
`triglycerides at
`daily doses of
`and
`
`daily krill
`28 percent
`pO.O25 and 27
`percel..t p0 0228
`
`oil
`
`decreasing
`
`from
`
`baseline
`
`levels of
`
`160.4 mg/dL and
`152.8 mg/dL to 116.1 mg/dL and
`Fish oil at
`
`respectively
`
`reduction of
`
`patients
`
`in the placebo
`
`9.8-percent
`
`decrease
`
`in
`
`percent
`
`112.3 mg/dL
`g/day did not achieve
`triglycerides 3.2%
`significant
`decreasing from 140.9 mg/dL to 136.4 mg/dL
`pO.239 Interestingly
`experienced
`group
`triglycerides pO.2l
`Blood glucose levels were reduced by 6.3
`from 105 mg/dL to 98 mg/dL pO.O25
`and 1.5
`in patients
`
`krill oil daily
`receiving
`from 92 mg/dL to 88 mg/dL
`and
`
`0.5
`
`These patients main
`krill oil daily Table
`mean total cholesterol
`level of 192.5 mg/
`tained
`percent pO.000 from
`dL
`reduction of
`baseline LDL was further reduced from baseline
`reduction from 233 mg/dL to
`by 44 percent
`107.5 mg/dL pO.000
`moderate
`HDL was seen from 36 percent
`increase at 90 days
`to 33 percent
`after 180 days of treatment which
`was still
`significant
`pO.000 Triglycerides
`were slightly decreased
`from baseline
`reduction of 25 percent
`further to
`pO.000 compared
`to the 12-percent
`observed after 90 days of treatment Blood glu
`from baseline
`cose decreased
`pO.2O versus
`days
`
`decrease
`
`in
`
`increase from baseline
`
`reduction
`
`by 6.6 percent
`
`the 6.3-percent
`
`decrease
`
`at 90
`
`Discussion
`
`Arteriosclerosis
`
`is the generic term for
`in which arterial walls become
`
`number of diseases
`
`thickened and lose elasticity with atherosclerosis
`important With its ef
`being considered the most
`and other vital
`fects on the brain heart kidneys
`and despite medical ad
`organs and extremities
`and
`atherosclerotic
`heart
`disease
`vancements
`stroke combined
`
`remain the number one cause of
`
`morbidity and mortality in the United States
`Canada and most Western
`
`countries.22
`
`and
`
`5.6 percent
`pO.Ol
`
`in those
`
`receiving
`
`krill oil
`
`daily
`
`daily dose of
`
`fish oil reduced blood
`
`from 90 mg/dL to 87 mgi
`glucose by 3.3 percent
`dL pO.275 Placebo treatment
`resulted in non
`significant blood glucose increase of 0.1 percent
`from 92 mg/dL to 93 mg/dL pO.75O
`The between-group
`comparison
`krill oil daily was significantly more
`than
`in reducing glucose and
`LDL whereas
`krill oil demonstrated
`
`and 1.5
`
`effective
`
`fish oil
`
`and
`
`showed
`
`significantly
`
`greater
`
`to
`
`fish oil Both
`
`reduction of glucose triglyc
`and LDL compared
`erides
`fish oil and krill oil performed significantly better
`than placebo
`of glucose trig
`for the regulation
`and HDL
`total cholesterol
`As mentioned previously patients receiv
`daily krill oil continued for an
`and 1.5
`
`lycerides
`
`ing
`
`other
`
`12 weeks with
`
`lower maintenance
`
`dose of
`
`Alternative Medicine Review
`
`Volume
`
`Number
`
`2004
`
`Page 425
`
`Copyright2004 Thorne Research
`
`Inc All Rights Reserved No Reprint Without Written Permission
`
`NEP877ITC-00040891
`
`Page 7
`
`

`
`CX Page
`
`Krill oil
`
`is
`
`complex combination
`multiple active ingredients with synergistic bio
`activity The exact mechanism of action for krill
`
`of
`
`lipid-
`
`krill oil
`
`oils lipid-lowering
`effects is not yet entirely clear
`However krill oils unique biomolecular profile
`of omega-3 EPA/DHA fatty acids already incor
`porated into phospholipids has exhibited
`lowering effect on the level of the small
`intestine
`from other known
`which distinguishes
`Werner et al demon
`
`lipid-lowering
`
`strated essential
`
`principals.89
`fatty acids in the form of phos
`to essential
`fatty acids as
`pholipids were superior
`
`the satu
`
`0.0519
`
`erosclerosis
`
`selective
`
`in significantly
`triglycerides
`decreasing
`and
`rated fatty acid ratios of liver triglycerides
`phospholipids each 0.05 while significantly
`ofthe
`the phospholipid concentrations
`increasing
`long-chain PUFAs
`LDL oxidation
`is believed to increase ath
`through high serum LDL levels
`in
`ducing LDL particles to migrate into subendothe
`by which LDL particles
`hal space The process
`are oxidized begins with lipid peroxidation fol
`lowed by fragmentation to short-chain
`aldehydes
`At the same time lecithin is converted to lyso
`for mono
`chemotactic agent
`lecithin
`cytes which become macrophages
`ingest oxi
`that
`dized LDL The new macrophage
`becomes en
`gorged with oxidized LDL cholesteryl
`esters and
`becomes
`foam cell Groups of foam cells
`of atheroscle
`
`In the United States
`
`cardiovascular
`
`dis
`
`for males
`
`has mortality rate of 39.9 percent
`percent dif
`and 43.7 percent
`15-21
`for females
`from malignant disease which ranks sec
`that 59.7 million Americans
`
`ease
`
`ference
`
`ond.22 It is estimated
`
`have
`
`dis
`
`heart
`
`one or more forms of cardiovascular
`ease.22 Of the population with self-reported
`disease 56-64 percent
`restricted activity
`report
`23-37 percent
`require one or more disability days
`are unemployed be
`per week and 28-34 percent
`The primary lesion
`cause of disability or illness.22
`of atherosclerosis
`is the fatty streak which even
`fibrous plaque Numerous
`tually evolves into
`randomized
`trials have proven
`lowering se
`rum cholesterol
`slows or reverses progression
`of
`coronary artery disease CAD and reduces coro
`nary events.22-29
`
`that
`
`EPA and DHA or
`daily intake of 1-3
`fish oil is currently recommended to reduce
`diseases.2223 Neverthe
`the risk of cardiovascular
`
`3-9
`
`studies evaluating the effects
`less epidemiological
`of fish oil on coronary heart disease
`dictory ranging from reverse associations
`
`are contra
`
`to vir
`
`tually no effect
`
`to
`
`beneficial
`
`effect.30-33
`
`sue in the efficacy
`
`One is
`of EPA/DHA may be the
`of these
`fatty acids
`bioavailability
`recent study demonstrated in vivo PUFA
`such
`
`on several
`
`factors
`
`depends
`bioavailability
`as the type of lipids in which
`
`they are esterified
`
`form
`
`their physical
`
`state i.e lipid solution
`
`or colloidal
`
`particle systems and the presence of co-ingested
`lipids.8 In vivo PUFA absorption
`was evaluated
`lymph of duct
`by fatty acid analysis of thoracic
`
`cannulated rats after intragastric feeding of dietary
`
`fats.9 Evidence
`
`demonstrates oral essential
`
`fatty
`
`ids is more effective
`
`acid supplementation in the form of phospholip
`than triglycerides in increas
`of long-chain PUFAs in liver
`ing concentrations
`and brain.89 DHA is better absorbed when de
`livered by liposomes than by fish oil relative lym
`and 65 pcr
`to 91 percent
`
`cent after
`
`phatic absorption
`equal
`liposome and
`fish oil administration
`of DHA
`The best bioavailability
`respectively
`delivered by liposomes is revealed by an increase
`in DHA proportions
`in both
`and phospholipids
`
`triacylglycerols
`
`lymphatic
`
`compared
`
`to
`
`fatty streak
`
`the earliest
`
`indication
`
`rosis.3435
`
`The unique molecular composition ofkrill
`oil with its abundance
`of phospholipids and anti
`
`oil
`
`oxidants may explain the significant effect ofkrill
`for blood lipid regulation In comparison
`to
`lowered blood lip
`
`fish oil knIl oil significantly
`
`ids at
`
`lower doses
`The effect of fish oil on cardiovascular
`
`disease
`
`is tempered by the presence of methyl-
`the U.S Food and
`mercury in many fish.33 In fact
`Drug Administration has advised pregnant women
`and women who may become pregnant not
`to eat
`tilefish shark or
`swordfish king mackerel
`from locally contaminated areas.36 Therefore
`fatty ac
`may be prudent to obtain these essential
`ids via supplementation Krill oil and most
`
`fish
`
`it
`
`fish
`
`fish oil diet.89
`
`are molecularly distilled
`oil concentrates
`move heavy metals
`
`to re
`
`Page 426
`
`Alternative Medicine Review
`
`Volume
`
`Number
`
`2004
`
`Copyright2004 Thorne Research
`
`Inc All Rights Reserved No Reprint Without Written Permission
`
`EP877ITC-00040892
`
`Page 8
`
`

`
`CX Page
`
`Hansen HS Olsen SE Dietary n-3-fatty
`acids prostaglandins and prolonged
`gestation
`
`in humans Prog ClinBiolRes 1988
`
`317
`JM Shih
`Lee TH Mencia-Huerta
`of exogenous
`arachidonic
`and docosahexaenoic
`
`Effects
`
`et al
`
`acids
`
`eicosapentaenoic
`on the generation of 5-lipoxygenase pathway
`human
`
`products
`
`by ionophore-activated
`
`neutrophils JClin Invest 1984
`acid intake Eur Cliii ih4tr 1995 16
`1996 Article in Danish
`
`Deutch
`
`in Danish women
`pain
`correlated with low n-3 polyunsaturated fatty
`
`Menstrual
`
`Deutch
`
`Painful menstruation and
`
`low intake
`
`of n-3 fatty acids Ugeskr Laeger
`
`Biro FM Kottenhahn RK Rosenthal
`Harel
`SL Supplcmcntation
`with omcga-3 polyun
`saturated fatty acids in the management
`of
`Am Obstet
`
`dysmenorrhea in adolescents
`
`Gynecol 1996
`
`Salem
`
`system
`
`Jr Niebylski CD The nervous
`has an absolute molecular
`species requirement
`for proper function Md Mernbr Biol
`1995 12131-134
`
`Blanchet
`
`Lemieux
`
`et al n-3
`
`Conclusion
`
`Atherosclerotic
`
`cardiovascular
`
`disease
`
`is
`
`maj or health problem in the Western world with
`CAD being the leading
`cause of mortality in the
`United
`States
`Extensive
`observational
`associate high CAD
`data strongly
`total and LDL cholesterol
`and low
`risk to elevated
`levels of HDL cholesterol
`evidence
`has established
`
`Extensive clinical trial
`
`that
`
`favorably
`
`altering
`
`epidemiologic
`
`dyslipidemias produces
`CAD end points.5-7
`The results of this clinical trial demon
`
`clear
`
`improvements
`
`in
`
`strate
`
`than
`
`krill oil are signifi
`EPA/DIJA fish oil
`
`that daily doses of 1-3
`cantly more effective
`in the management of hyperlipidemia Further
`dose of 500 mg krill oil
`more maintenance
`for long-term regulation of
`effective
`significantly
`blood lipids The unique molecular composition
`of krill oil which is rich in phospholipids
`fatty acids and diverse antioxidants
`surpasses
`the profile of fish oils and offers
`superior ap
`ofrisk for cardiovas
`proach toward the reduction
`cular disease
`
`is
`
`omega-
`
`10
`
`11
`
`12
`
`13
`
`14
`
`References
`
`factors
`
`Dewailly
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`among the Inuit of Nunavik Am Clin
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`Holub BJ Clinical
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`
`nutrition
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`
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`
`Harris WS Fish oils and plasma lipid aM
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`lipoprotein metabolism
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`critical
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`Jeppesen
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`Hem HO Suadicani
`Gyntelberg
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`Chair Michael
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`Schneider
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`Kelley YE et al The
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`Treatment
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`Alternative Medicine Review
`
`Volume
`
`Number
`
`2004
`
`Page 427
`
`Copyright2004 Thorne Research
`
`Inc All Rights Reserved No Reprint Without Written Permission
`
`EP877ITC-00040893
`
`Page 9
`
`

`
`20
`
`Health and Welfare Canada
`
`Promoting
`
`Discussion
`Paper Minister
`Healthy Weights
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`Ontario 1988
`
`index WI
`Garrow JS Webster
`Quetelets
`H2 as measure of fatness mt Obes
`1985
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`Krauss RM Eckel RH Howard
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`revision 2000
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`Dietary Guidelines
`for healthcare professionals from the Nutrition
`Committee of the American Heart Association
`Stroke 2000 2751-2766
`Martin JL et al
`risk factors and
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`Salen
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`diet traditional
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`
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`Jimenez FJ et al Omega-3
`
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`Linoleic and eicosapentaenoic
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`Hennekens CH Sacks FM et al
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`Salonen JT Seppanen
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`Schwab US Jones PJ et al Impact
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`Gillum RF Mussolino
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`death from
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`2000 237-244
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`
`Alternative Medicine Review
`
`Volume
`
`Number 44 2004
`
`Copyright2004 Thorne Research
`
`Inc All Rights Reserved No Reprint Without Written Permission
`
`EP877ITC-00040894
`
`and 20-year mortality from
`consumption
`coronary heart disease NEnglfMed
`
`1985
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`OrenciaAJ
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`1997 1046-1053
`Willett WC et al Fish and
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`and risk of coronary
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`ornega-3
`heart disease in women JAMA
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`Dietary intake of marine n-3 fatty acids fish
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`
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`Physicians Health Study
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`JE Rosner
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`
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`
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`Page 10