isbn hb seafood and chronic cond lit review 16th may...
TRANSCRIPT
1
Health benefits of seafood for the prevention and management of chronic conditions:
A systematic review
Professor Alexandra McManus
Project No. 2013/711
March 2014
2
Health benefits of seafood for the prevention and management of chronic conditions: A systematic review March 2014 Authors
Professor Alexandra McManus Director, Centre of Excellence Science Seafood & Health (CESSH) Curtin University 7 Parker Place Technology Park Western Australia 6102 Jessica Pohlenz-‐Saw Dietitian CESSH and Armadale Community Hospital Jennifer McManus Research Associate CESSH Dr Wendy Hunt Deputy Director, CESSH Contact Details Email: [email protected] Mobile: 0417 986 171 Suggested Citation: McManus A, Pohlenz-‐Saw J, McManus J, Hunt W. Health benefits of seafood for the prevention and management of chronic conditions: A systematic review. Centre of Excellence for Science Seafood & Health (CESSH), Curtin University Report # 31032014. ISBN 9780987208620
3
TABLE OF CONTENTS
1.0 INTRODUCTION ............................................................................................. 8
1.1 Seafood and Health ....................................................................... 8
1.2 Seafood and Nutrients ................................................................... 8
2.0 METHODS .................................................................................................... 15
2.1 Implementation of the Search Strategy ....................................... 15
3.0 RESULTS OF SYSTEMATIC LITERATURE REVIEW ............................................ 17
3.1 All Cause Mortality -‐ Summary of evidence .................................. 17
3.2 Alzheimer’s Disease (including dementia, cognitive function,
ageing) -‐ Summary of evidence ................................................... 19
3.3 Arthritis -‐ Summary of evidence .................................................. 20
3.4 Asthma, Coronary Obstructive Pulmonary Disease, Allergic Rhinitis
and Food Allergies -‐ Summary of Evidence .................................. 22
3.5 Attention Deficit Hyperactivity Disorder and Other Behavioural
Issues In Children -‐ Summary of evidence ................................... 23
3.6 Brain Development and Function -‐ Summary of evidence ............ 24
3.7 Cancer -‐ Summary of evidence ..................................................... 27
3.8 Cardiovascular Diseases -‐ Summary of evidence .......................... 29
3.9 Cystic Fibrosis -‐ Summary of evidence ......................................... 33
3.10 Diabetes -‐ Summary of evidence .................................................. 34
4
3.11 Kidney Disease -‐ Summary of evidence ........................................ 36
3.12 Liver Disease -‐ Summary of evidence ........................................... 37
3.13 Maternal and Child Health -‐ Summary of evidence ...................... 37
3.14 Mental Health and Behavioural Conditions -‐ Summary of evidence
.................................................................................................... 40
3.15 Metabolic Syndrome -‐ Summary of evidence ............................... 42
3.16 Osteoporosis -‐ Summary of evidence ........................................... 43
3.17 Overweight and Obesity -‐ Summary of evidence .......................... 45
3.18 Possible Health Risks -‐ Summary of evidence ............................... 46
4.0 CONCLUSIONS ............................................................................................. 49
5.0 REFERENCES……………………………………………………………………………………………….51
5
Glossary of Terms AD
ADHD
ALA
AR
BMI
CESSH
CF
CHD
COPD
CVD
DHA
EPA
FSANZ
GI
HDL
HIV
LDL
MI
n-‐3s
NHMRC
NSAID
Omega-‐3s
Omega-‐6s
PUFAs
RA
RDI
SFA
TG
T2DM
VHDL
Alzheimer’s Disease
Attention deficit hyperactivity disorder
Alpha-‐linolenic acid
Allergic Rhinitis (hay fever)
Body mass index
Centre of Excellence Science Seafood & Health
Cystic fibrosis
Coronary heart disease
Chronic obstructive pulmonary disease
Cardiovascular disease
Docosahexaenoic acid
Eicosapentaenoic acid
Food Standards Australia and New Zealand
Glycaemic index
High density lipoproteins
Human Immunodeficiency Virus
Low density lipoproteins
Myocardial infarction
Omega-‐3s (PUFAs)
National Health & Medical Research Council
Non steroidal anti inflammatory drugs
Omega 3 poly unsaturated fatty acids
Omega 6 poly unsaturated fatty acids
Poly unsaturated fatty acids
Rheumatoid arthritis
Recommended daily intake
Saturated fatty acids
Triglyceride
Type 2 diabetes mellitus
Very high density lipoproteins
6
Non-‐Technical Summary
2013/711 Health benefits of seafood for the prevention and management of chronic conditions: A systematic review PRINCIPAL INVESTIGATOR: Professor Alexandra McManus ADDRESS: Centre of Excellence for Science, Seafood and Health (CESSH) Curtin University 7 Parker Place, Technology Park WA 6102
PO Box U1987, Perth WA 6845 Telephone: 08 9266 2115 Fax: 08 9266 2508
OBJECTIVES:
The objectives of the project are:
1. To conduct a systematic review of the health benefits of seafood in relation to chronic
conditions.
2. Present evidence from systematic review by chronic condition as
• summary dot points and
• text bites in layman’s language (that could be used directly by the industry).
METHODS:
A systematic review of literature was conducted using a comprehensive research strategy to
identify evidence supporting the health benefits of seafood for the prevention and
management of chronic conditions. A total of 526 publications met the selection criteria
based the list of terms within the search strategy. Two reviewers independently reviewed
and assessed each publication and rated the strength of evidence based on the National
Health and Medical Research Council (NHMRC) Hierarchy of Evidence. The ratings of the two
reviewers were then compared and those with different ratings were discussed and an
agreed level of evidence assigned. A total of 281 publications had a sufficiently high level of
evidence linking seafood to the prevention or management of chronic health conditions,
thus were included in the review.
RESULTS:
Significant levels of evidence supported the regular consumption of seafood for the
prevention and management of several chronic conditions. The strongest evidence is around
the reduction of risk for all cause mortality, coronary heart disease (CHD), diabetes, mental
health disorders, and nutrition related cancers. There is also strong evidence supporting the
benefits of regular seafood consumption that is high in Omega-‐3s (n-‐3), for optimal brain
7
development and function, management of inflammatory conditions (such as arthritis,
asthma and hay fever) plus control of inflammation associated with lung cancer and chronic
pulmonary obstructive disorder (COPD), a common condition associated with impaired lung
function.
Evidence shows the regular consumption of seafood high in Omega-‐3s delays the onset of
Alzheimer’s disease (AD) in susceptible people and slows the progression of the disease in
those already affected. There is emerging evidence supporting a seafood rich diet for people
with cystic fibrosis (CF), kidney disease, liver disease and osteoporosis. Further, eating
seafood as the main protein source can provide significant benefits in the dietary
management of overweight and obesity.
There are many health benefits that can be gained from ingesting Omega-‐3s either through
eating seafood or via supplementation. However, seafood also contains many nutrients that
help the body to perform efficiently and effectively. These include:
• lean protein for cell repair and energy
• vitamin D and calcium for bone and teeth health
• calcium for muscle, heart and nerve function
• selenium to prevent cell damage and promote healing and immune function
• iodine (together with selenium) to regulate thyroid function and metabolism
• iron to help the blood carry oxygen to cells and for energy production and
• zinc to aid healing and for normal growth and development.
CONCLUSIONS:
This report provides a summary of evidence supporting the health benefits of seafood for
the prevention and management of chronic conditions. A balanced diet high in seafood, aids
in the prevention and management of many of the common chronic conditions affecting
people today. The promotion of healthy eating should be integral to health promotion
initiatives across the lifespan, not only to improve better long term health outcomes, but
also to reduce the significant health care costs associated with the high prevalence of
nutrition-‐related chronic conditions in Australia and around the world.
OUTCOMES ACHIEVED TO DATE • Systematic review of literature on the health benefits of seafood for the prevention and
management of chronic conditions.
• Evidence about the links between seafood and chronic conditions presented in layman’s
language of seafood to a number of common chronic conditions affecting humans.
8
1.0 INTRODUCTION
1.1 Seafood and Health
In the 1950’s it was noted that Eskimos native to both Greenland and Alaska had a
low incidence of heart disease despite having a diet high in oil. They also had a lower
incidence (new cases) and morbidity (existing cases) of coronary heart disease (CHD).
The causal nutrient thought to be ingested daily by all of these populations was
Omega-‐3s from seafood. Since this discovery in the 1950s, there has been intense
interest in finding what other health benefits could be gained from marine sourced
Omega-‐3 long chain polyunsaturated fatty acids (PUFAs) (Omega-‐3s).1 We now know
that the consumption of oily fish, seafood and fish oils have been positively linked
with brain development, cognitive function and a reduced risk of many chronic
conditions including coronary heart disease, some cancers, diabetes, arthritis,
dementia and Alzheimer’s Disease.1-‐7
Although much of the research has focussed on Omega-‐3s and its many health
benefits, other nutrients in seafood also provide significant health benefits. For
example, seafood is an excellent source of lean protein. The superior macronutrients
combined with healthy Omega-‐3s, make seafood a superfood for health. In addition,
seafood offers a wide array of highly bio micronutrients. In fact, seafood is the best
dietary source of many nutrients.6
1.2 Seafood and Nutrients
The key nutrients in seafood that provide benefits to human health are Omega-‐3s,
protein, vitamins A, B12, D and E, iodine, selenium, calcium, zinc and iron.
Marine Sourced Omega-‐3s
Evidence clearly shows the link between health benefits and consumption of seafood
high in Omega-‐3s. These benefits include: brain and retinal (eye) foetal development;
cognitive development; mental health improvements (depression, schizophrenia,
dementia and attention deficit hyperactivity disorder (ADHD); lower risk of CHD and
9
protection against heart arrhythmia; plus greater arterial plaque stability and anti-‐
thrombotic properties. There is also evidence of the role of Omega-‐3s in maintaining
immune function and reducing inflammation for the treatment of all forms of
inflammatory arthritis. Oily fish are the richest source of Omega-‐3s. The two Omega-‐
3s with proven health benefits are eicosapentaenoic acid (EPA) and docosahexaenoic
acid (DHA). The most abundant source of EPA and DHA are marine based sources. It
should be noted that there is another Omega-‐3 fatty acid that offers some health
benefit being alpha-‐linolenic acid (ALA), which is found in some plants. ALA must be
converted to EPA and DHA after ingestion to be of use to the body. Herein lies the
problem. Conversion rates of ALA to EPA and DHA are typically very low at around 3-‐
8% making it very difficult to consume enough plant-‐based ALA to gain any
substantial benefit. Clearly the consumption of Omega-‐3s from seafood is the best
way to gain many additional health benefits.
For those who do not or cannot eat seafood, Omega-‐3 fortified foods and
supplements are, however, recent research indicates that there are dramatic
variations in the benefits offered from these products. For example, the shelf life of
Omega-‐3 fortified foods and supplements have been questioned in light of their
susceptibility to oxidation. By-‐products of oxidation such as peroxides, present
safety concerns to humans. Eating seafood is the best way to gain the significant
health benefits offered from Omega-‐3s. Those choosing to get their Omega-‐3s from
supplements or fortified foods should make sure they consider if the products are
from reputable sources, been stored correctly and are well within their use by dates.
Protein
Approximately half of the human body’s dry weight is comprised of protein. It is
essential for human health and survival plus is a vital macronutrient that must be
consumed regularly to meet the needs of the human body. Proteins are large
molecules that serve as foundations for most of the body’s cells. They are vital for
the development and maintenance of muscle, blood, skin and bone.
10
Protein plays an important role in antibody production, regulation of body
composition, glucose metabolism, satiety, cell signalling, gastrointestinal health,
bacterial flora and digestive function. It also provides the basis for production of
some enzymes and hormones such as adrenaline, thyroid hormones and insulin.
Protein is a valuable source of energy. Animal sourced dietary proteins tend to be
complete sources of protein; that is, they contain the full complement of essential
amino acids, the building blocks of all proteins. Fish protein tends to be high in lysine,
sulphur containing amino acids and threonine: essential amino acids that are limited
in cereal-‐based diets. Evidence suggests that marine proteins are superior to other
protein sources and offer some protection against many lifestyle diseases
(overweight/obesity) due to their amino acid compositions. Furthermore,
consumption of seafood protein has been positively associated with increased
insulin sensitivity (in diabetics), reduced inflammation and lower blood pressure.
Vitamin D
Vitamin D is important in regulating calcium and phosphorous in bone mineralisation.
It is also vital to thyroid function, insulin production, immunity, skin conditions,
muscle strength and has been linked to the prevention of some cancers.
Widespread awareness of the causal link between sun exposure and skin cancer in
Australia and New Zealand has diminished the amount of vitamin D that the general
population obtains from the sun. Sunscreen and clothing act as barriers preventing
not only sun damage but also the synthesis of vitamin D. Vitamin D deficiency and
rickets (osteomalacia) are current health concerns across Australia and New Zealand.
At risk populations include dark-‐skinned individuals, seniors, people with limited
mobility and those who cover themselves when outdoors.
The food chain of marine animals tends to concentrate vitamin D and makes seafood
the best dietary source of vitamin D. Prevention of vitamin D deficiency can be
achieved with a diet high in oily fish together with limited sunlight exposure (around
10 minutes each day).
11
Iodine
Iodine is vital for the effective functioning of the thyroid gland and for thyroid
hormone production. The thyroid facilitates normal growth, metabolism, cell oxygen
consumption and the development of the central nervous system. Up until the early
1990s, the iodine status of Australians was satisfactory, however the iodine intake of
the Australian population is now considered inadequate.
Iodine is found in most seafood, with shellfish containing the most abundant
quantities. Fish and seafood have the highest concentration of iodine relative to
other foods commonly consumed. Regular seafood consumption as a part of a
healthy diet will improve iodine status.
Selenium
Selenium is protective against oxidative stress, which is a primary cause of cellular
damage. It also assists in regulating the function of the thyroid (together with iodine)
and supports healthy immune function. Selenium is present in most finfish. Selenium
in fish is highly bio suggesting that fish is a superior source of dietary selenium
relative to other sources.
In addition to the nutritional benefit of selenium consumption, emerging research
suggests that selenium acts as a counteractive agent to mercury. It is possible that
methylmercury accumulation in some fish populations may be moderated by
selenium.
Calcium
Calcium is important for developing and maintaining bones and teeth, as well as
supporting healthy function of muscles, nerves and the heart. Skeletal calcium serves
as a reservoir for the supply of calcium to the body when required. If calcium is not
consumed regularly these stores are depleted affecting bone health. Adequate
dietary calcium is required throughout life to prevent loss of bone mineral density,
fragility fractures, osteopenia and osteoporosis.
12
Bony fish such as sardines and tinned salmon are rich in calcium. The ingestion of at
least 250g of seafood per week (2-‐3 serves) has been associated with greater bone
mineral density.
Excessive dietary fibre intake and alcohol use can interfere with calcium uptake in
the body. Effective calcium absorption also depends on adequate levels of vitamin D
within the body.
Vitamin B12
Vitamin B12 is important to DNA synthesis (cell replication), red blood cell production
and neurological function. Deficiency of vitamin B12 is associated with megoblastic
anaemia (loss of red blood cells), nervous system disorders, myelopathy (spinal cord
disease), memory impairment, dementia, depression and cerebrovascular (blood
vessels that supply the brain) disorders. Clams, octopus, oysters, fish and fish roe are
excellent sources of vitamin B12. Researchers have identified that dietary vitamin B12
sourced from fish is more bio than that from meat and eggs.
Vitamin A
Vitamin A plays an important role in supporting normal vision, reproduction, bone
growth and immune function. It is also essential to healthy respiratory and urinary
tract linings, and to the health of skin and mucous membranes.
Most fish and shellfish contain vitamin A, with the best marine sources being oily fish.
Animal sourced vitamin A (retinol) is efficiently absorbed and used by the body.
Plant sources of vitamin A (β-‐carotene) are less efficiently absorbed.
Vitamin E
Vitamin E is a highly efficacious antioxidant that is important to the skin, nervous
system, heart and circulatory system. Vitamin E protects vitamins A and C by
preventing their oxidation. The highest marine source of vitamin E is oily fish.
13
Zinc
While only small amounts of this essential trace element are required, zinc acts as a
catalyst for over 100 specific enzymes necessary for human metabolism. Zinc plays a
role in optimal growth and development, and in the efficient functioning of the
immune system. Zinc deficiency may result in stunted growth, vulnerability to
infection and adverse pregnancy outcomes.
Zinc rich food should be consumed regularly so that optimal zinc levels are
maintained in the body. Zinc binds to protein, therefore seafood -‐ a source of both
zinc and protein -‐ optimises the body’s ability to use dietary zinc. Oysters are known
to be one of the richest natural sources of zinc.
Iron
Iron plays a vital role in the transportation of oxygen throughout the body in the
blood and is associated with growth, healing and immune function. It is also critical
for energy production and cell replication within the body. Research suggests that
many Australian women are not consuming adequate levels of iron, particularly
during important life events such as pregnancy and menopause. Increasing the
consumption of iron rich seafood within a balanced diet can play an important role
in addressing this imbalance. Furthermore, the body more readily uses iron found in
seafood than plant sources.
14
Summary
In summary, Omega-‐3s are essential for human health. Humans cannot make them
in sufficient amounts so they need to consume them everyday. Seafood is the best
nutritional source of Omega-‐3s with evidence of health benefits to humans.
However, there is much more to seafood than just Omega-‐3s. It is a superfood
providing an array of nutrients that help to keep us healthy.
Seafood is a great source of:
• lean protein to build strong muscles and bones
• vitamin D for bone strength and healthy immune systems
• iodine essential for thyroid function, growth and for the nervous system
• selenium to protect cells, regulate thyroid function and support our immune
system
• calcium for bone growth and prevention of osteoporosis
• vitamin B12 for blood production, cell development, and brain and nervous
system function throughout life
• vitamin A for heart, eye, kidney and lung health, plus cell production and
function
• vitamin E for smooth muscle growth, brain function, protection of cells from
damage and to help the body to use Omega-‐3s
• zinc for normal growth and to help the body to use protein
• iron to allow the body to transport oxygen in red blood cells, for energy
production and for growth, healing and immune function.
15
2.0 METHODS
A research associate experienced in seafood and health systematic reviews
conducted an initial literature search and developed a list of possible search terms.
The research team associated with this project reviewed the search terms and
consulted a senior librarian to develop a comprehensive search strategy. The search
strategy was informed by the following key terms: seafood, health, specific and
generalised chronic conditions, health benefits and nutrition. Search terms were
used individually and in combination. The search strategy was used to guide the
systematic review of evidence supporting the health benefits of seafood for the
prevention and management of chronic conditions.
Using the search strategy, published peer-‐reviewed articles (in English) were sourced
from the following databases: Archive of Life Sciences; Proquest; PubMed; Science
Direct; Taylor and Francis; The Cochrane Collaboration; Web of Knowledge; Web of
Science; and Wiley Interscience. Other sources of information searched were:
national and international seafood-‐based databases; seafood industry websites or
databases; major national and international academic libraries; electronic sources of
information (e.g. Google, Google Scholar, international websites); Departments of
Health within Australia; and educational institutions.
2.1 Implementation of the Search Strategy
The search strategy identified 526 publications that met the search criteria. The full
version of each article was sourced and an Endnote database file created of these
references. Key search words were linked to each reference in Endnote to assist in
sorting and summarising the published evidence.
Publications were then independently reviewed by two trained researchers, one an
accredited dietitian and the other a very experienced reviewer who has completed
the Cochrane Systematic Review training program (considered to be the gold
standard for the conduct of systematic reviews).
16
The NHMRC Evidence Hierarchy was used as the framework for assessing the 526
journal articles (www.nhmrc.org.au) identified as meeting the criteria for possible
inclusion in this review. The NHMRC Evidence Hierarchy framework is a valid tool for
the effective management and critical review of large amounts of evidence.
The levels of evidence outlined in the NHMRC framework for assessment include:
• I -‐ high level systematic reviews -‐ randomised control trials and similar studies
• II -‐ randomised controlled trial
• III-‐1 -‐ pseudo-‐randomised controlled trials
• III-‐2 -‐ comparative studies with concurrent controls
• III-‐3 -‐ comparative studies without concurrent studies and
• IV -‐ case series with either post-‐test or pre-‐test/post test outcomes.
Following the assigned level of evidence to each study by the two researchers
(independent of each other), their assessments were compared. Where differences
in the level assigned was evident, the two researchers discussed the reasons for their
assigned score and made a joint decision about what evidence level should be
assigned to each of these articles. The articles were then sorted by health or chronic
condition, critically reviewed and the evidence summarised. The main outcomes of
each of the publications included in the systematic review are stated in point form in
the results section of this report. A total of 281 articles met the criteria thus were
included in the review
17
3.0 RESULTS OF SYSTEMATIC LITERATURE REVIEW
Key findings from the systematic literature review are presented herein by either
health or chronic conditions. Evidence for each chronic condition consists of a
general summary of evidence (boxed) followed by a list (in dot point form) of the
main outcomes of each of the studies included in this review. References are listed
at the end of this report. Only those studies with strong and credible scientific
evidence (using the NHMRC Hierarchy of Evidence levels as a guide) are included in
this review (see the methods section).
3.1 All Cause Mortality -‐ Summary of evidence
There are significant risk reductions in all cause mortality associated with the
consumption of 1-‐2 serves of seafood each week especially for: coronary health
diseases (CHD); inflammatory conditions; neurodegenerative diseases; mental health
and behavioural disorders; immune responses; and some cancers.
Health benefits are gained from ingesting Omega-‐3 polyunsaturated fatty acids
(Omega-‐3s) found in abundance in most seafood, particularly oily fish. The Omega-‐3s
that provide benefits are EPA and DHA. The best dietary source of EPA and DHA is
seafood. Seafood is also a readily digestible source of lean protein and is a good
source of vitamin D, selenium and iodine. Evidence shows that individuals who eat
one or more serves of seafood per week (as part of a healthy diet) report a higher
level of health compared with non-‐seafood eaters.
All Cause Mortality – Main outcomes of studies
• Regular fish and Omega-‐3 consumption is associated with a significant reduction
of risk of total mortality. One to two serves of fish per week, especially those
high in Omega-‐3s, decrease the risk of total mortality by 17%. 15
• Observational evidence has shown that higher circulating individual and total
Omega-‐3 levels are associated with lower total mortality, especially CHD death,
in older adults. 16
18
• When used as a secondary prevention strategy, Omega-‐3s appear to modestly
reduce all-‐cause mortality and restenosis (recurrence of blocked arteries or
heart values). 8
• Early supplementation of 1 g/d of Omega-‐3s after a myocardial infarction (MI) is
recommended to reduce the risk of all-‐cause mortality. 9, 10
• There is clear evidence that Omega-‐3s (particularly EPA and DHA) are beneficial
to human health. Evidence shows they exert benefits on cardiovascular heath,
inflammatory disorders, neurodegenerative diseases, mental health,
behavioural disorders, immune responses, age related factors and some
cancers. 1, 7, 11, 12
• The individual metabolic and physiological effects of EPA and DHA vary in the
body. 13
• The body processes marine sourced Omega-‐3s more efficiently than
supplements. 14
• The health benefits of seafood consumption go beyond those derived from the
Omega-‐3 PUFA, with seafood also providing high quality protein, vitamin D,
selenium, iodine and other bioactive components. 17-‐20
• Cross sectional data shows that individuals who consume fish at least once a
week have higher self-‐reported general health. 21
• Evidence strongly supports the establishment of a RDI (Recommended Daily
Intake) of Omega-‐3s.23
• The 2-‐3 serves of seafood/fish recommended each week should include at least
one serve high in Omega-‐3’s in order to attain sufficient Omega-‐3s for human
health. 22
• Many (USA) adults are not consuming the recommended levels of Omega-‐3s in
their diet. Governing authorities should consider supplementation in food or the
promotion of fish oil capsules to assist the population to meet the
recommended intake levels.24
19
3.2 Alzheimer’s Disease (including dementia, cognitive function, ageing) -‐ Summary of evidence
A diet high in fish, nuts, salad dressings, poultry, tomatoes, fruit, cruciferous (e.g.
broccoli, brussels sprouts, cabbage) and dark green leafy vegetables is strongly
associated with a lower risk of AD. Post mortem examinations of the brains of
people with AD show a lack of DHA in the grey matter. Evidence shows that eating at
least 2 serves of Omega-‐3 rich seafood each week reduces the risk of dementia,
delays the onset of AD in susceptible people and slows cognitive decline. A balanced
diet high in seafood has the potential to significantly reduce the public health burden
of AD and contribute to healthy ageing.
Alzheimer’s Disease -‐ Main outcomes of studies
• Research has revealed that a diet high in fish, nuts, salad dressings, poultry,
tomatoes, fruit, cruciferous and dark green leafy vegetables is strongly
associated with a lower risk of AD. 25
• Reduced risk of dementia is thought to be associated with the consumption of
marine sourced Omega-‐3s: EPA and DHA. 26
• Post-‐mortem examinations have revealed that the brains of persons with AD
contain less DHA in the grey matter of the frontal lobe and hippocampus. 27
• Large population based studies consistently reveal that Omega-‐3s retard
cognitive decline over time. 28
• Elevated levels of lipid peroxidation have been observed in people with mild
cognitive impairment and AD. Higher intakes of EPA and DHA appear to reduce
lipid peroxidation amongst the elderly. 29
• Dietary Omega-‐3s are shown to be beneficial in balancing the ratio of Omega-‐3s
to Omega-‐6s in the brains of normal subjects, thereby reducing the potential of
damage to the brain. 26
• Emerging evidence suggests that genetic variations may influence the effect of
EPA and DHA on cognitive decline. 30
20
• Promotion of the evidence to increase the consumption of sustainable seafood
as part of a healthy diet has the potential to significantly reduce the human and
public health burden of AD in the future. 2
• Evidence supports 2-‐3 serves of fish each week can prevent cognitive decline. 31
• Omega-‐3s promote active cognitive function in seniors. 32
• In post menopausal women, high levels of EPA and DHA in red blood cells is
associated with reduced atrophy of the brain during normal ageing.33
3.3 Arthritis -‐ Summary of evidence
Seafood high in Omega-‐3s is beneficial in the management of inflammation within
the body. Arthritis is a condition that results in significant inflammation around the
joints of the body. It is often painful and extremely debilitating, impacting on a
person’s ability to do everyday activities. Moderate to high intake of oily fish high in
Omega-‐3s appears to be protective against osteoarthritis and rheumatoid arthritis
(RA). Evidence supports daily consumption of oily fish such as fresh salmon,
mackerel, herring or sardines for this debilitating condition. Daily ingestion of fish oil
also provides significant benefits to those with RA. Fish oil (1000 mg/day) is currently
used as an adjunct to approved medications for arthritis and can enhance the
effectiveness of conventional RA treatments.
Fish oil supplementation for people at risk of developing or who have arthritis,
should be prescribed by a medical practitioner as part of an overall medication
management plan.
Arthritis -‐ Main outcomes of studies
• Evidence shows that fish intake is beneficial in the management of inflammatory
diseases. 1, 34
• A number of molecular mechanisms demonstrating the anti-‐inflammatory effects
of Omega-‐3 PUFA have been proposed. 35
21
• Adequate levels of Omega-‐3 PUFA are important for appropriate immune system
responses. 36
• Dietary intakes of Omega-‐3s are associated with lower levels of inflammation.159
Supplementation of 1.25 g/day of Omega-‐3 PUFA for four months significantly
lowered levels of inflammatory molecules. 37
• Moderate to high intake of fish appears to be protective in RA. An increase of 30
g of oily fish per day (8 g fat/100 g fish – fresh salmon, mackerel, herring;
processed mackerel herring, sardines) has been associated with a 49% reduced
risk of developing RA. 38
• Dietary fish oil supplementation has demonstrable benefits for RA and other
inflammatory/ autoimmune conditions (e.g. bowel disease and immunoglobulin
A nephropathy) and may also reduce pharmacological dosages required to treat
RA. 39
• Supplementation of Omega-‐3 PUFA in children with juvenile idiopathic arthritis
reduces inflammatory responses, clinical manifestations and the required doses
of non-‐steroidal anti-‐inflammatory drugs (NSAID). 40
• Ingestion of Omega-‐3 fatty acid supplements has consistently shown
improvements in joint tenderness and swelling, amount and duration of morning
stiffness and disease activity in those with RA. 39, 40
• Fish oil is currently used as an adjuvant to approved medications for arthritis and
studies support its efficacy in conjunction with NSAIDs. Recent research shows
that supplementation of the Omega-‐3 fatty acid EPA enhances the effectiveness
of conventional RA treatments. 41 While consumption of fish and fish oil does not
prove efficacious in all cases, some individuals have been able to discontinue or
reduce NSAID therapy while continuing fish oil ingestion. 39, 42-‐45
• 1000 mg/day of Omega-‐3s significantly reduced triglyceride levels in patients
with active RA. 46
22
3.4 Asthma, Coronary Obstructive Pulmonary Disease, Allergic Rhinitis and Food Allergies -‐ Summary of Evidence
Evidence supports the anti-‐inflammatory benefits of a diet rich in Omega-‐3s. This is
true for asthma where Omega-‐3s reduce inflammation by positively impacting on
lipid profiles. Recent research suggests that eating fish, seafood or supplementing n-‐
3 PUFA during pregnancy may protect some children from asthma, eczema and food
allergies. Fish consumption in the first year of life is associated with a reduced risk of
asthma and allergic rhinitis (AR) (hay fever) in childhood. Children who eat fish at
least once a week have a reduced risk of respiratory conditions compared with
children who do not each fish. Children should be encouraged to eat a varied and
balanced diet with at least one serve of oily fish each week.
Asthma, COPD, Allergic Rhinitis and Food Allergies -‐ Main outcomes of studies
• An Omega-‐3s rich diet reduces inflammation associated with asthma by
positively manipulating lipid profiles. 47
• Recent research suggests that eating fish, seafood or Omega-‐3 supplements
during pregnancy may protect some children from asthma 48-‐51 eczema and food
allergies. 50
• Fish consumption in the first year of life is associated with a reduced risk of
asthma and allergic rhinitis in childhood. 52, 53
• Epidemiological studies in Australia reveal that school children who eat fish
more than once a week have one-‐third the risk of airway hyper-‐responsiveness
compared with children who do not eat fish regularly. 54
• Diets rich in Omega-‐3s, from either dietary sources or supplements, are
associated with a reduced risk of asthma and airway diseases. 49, 51, 55, 56
• Consumption of highly processed fish sticks during pregnancy significantly
increases asthma risk in children (odds ratio 2.04). This negative outcome is
thought to be associated with the trans fat content of the processed fish sticks. 48
23
• Emerging evidence indicates that Omega-‐3 supplementation can improve the
pulmonary function in athletes undertaking intense physical training. 57
• Observations have shown that adherence to a Mediterranean diet pattern
during pregnancy and childhood (which includes fish) may have protective
effects from asthma and allergic disorders in childhood. 58
3.5 Attention Deficit Hyperactivity Disorder and Other Behavioural Issues In Children -‐ Summary of evidence
Almost 4 in 100 children in Australia have ADHD. Research has shown that children
with ADHD often exhibit poor behaviours if they have low levels of circulating
Omega-‐3s. Diets high in Omega-‐3s have resulted in improvements in the behaviour
of children with ADHD. Omega-‐3s may also assist in the management of co-‐
morbidities associated with ADHD such as mood and impulsivity disorders,
oppositional defiance disorder, obsessive-‐compulsive disorder and depression.
Attention Deficit Hyperactivity Disorder and other Behavioural Issues In Children -‐
Main outcomes of studies
• Approximately 4 of every 100 children in Australia have ADHD (The Royal
Children's Hospital Melbourne www.rch.org.au). Significant co-‐morbidities of
ADHD include mood and impulsivity disorders, oppositional defiance disorder,
obsessive-‐compulsive disorder and depression. Sixty percent of these remain
throughout life. 59, 60
• Evidence of the role of seafood or fish oil supplements in the management of
attention disorders such as ADHD is mounting.60-‐66 Diets high in Omega-‐3s have
been shown to correlate with the marked improvement in the behaviours of
children with ADHD. 59, 60 Children with ADHD should, therefore, be encouraged
to consume Omega-‐3s. 67
• Low levels of Omega-‐3s may contribute to adverse ADHD symptoms.68 Further
research is required to confirm if Omega-‐3s could be an effective treatment for
ADHD and what levels are required to provide positive outcomes. 69
24
• Australian children do not consume the recommended levels of Omega-‐3s
(particularly DHA) required for optimum health benefits. This can be explained
by the low consumption of seafood/fish in children. 70
3.6 Brain Development and Function -‐ Summary of evidence
DHA and EPA are polyunsaturated fatty acids, essential to the development of the
brain during pregnancy and for optimal cognition as we grow. DHA is highly
concentrated in the brain. DHA and EPA support the composition and function of the
central nervous system. Adequate Omega-‐3 intake in the first year of life is
particularly important. Fish intake has been linked to academic performance.
Improvements are evident in processing speed, visual-‐motor coordination,
perceptual integration, attention and executive function.
There is good evidence showing that cognitive ability is influenced by the ratio of
Omega-‐3s (marine sourced) to Omega-‐6s (plant based) in the body. For example
higher levels of Omega-‐3s compared with Omega-‐6s is predictive of improved
cognition in children. Conversely, low levels of red blood cell Omega-‐3 is associated
with poor cognitive performance in children.
A diet high in seafood is associated with reductions in depression, behavioural
problems, mood and impulsivity disorders. There is emerging evidence that
adequate levels of Omega-‐3s in early childhood and into adulthood may prevent or
reduce aggression and hostility.
Headaches are one of the most common debilitating conditions in adults,
particularly for daily sufferers. There is strong emerging evidence that a diet high in
Omega-‐3s and low in Omega-‐6s can reduce the number of headache days per month
and reduce the duration of daily headaches in this population.
25
Brain Development and Function -‐ Main outcomes of studies
• DHA and EPA are essential for foetal and neonatal brain development and
maturation. Fatty acids accumulate quickly during periods of rapid brain growth
and development during gestation (particularly in the last trimester) and in the
first year of life. 71, 72
• During foetal development there is a large accumulation of Omega-‐3 PUFA in
retinal membranes. There is also some evidence supporting maternal DHA
intake as beneficial to the visual development of the foetus with benefits still
detected in late childhood. 73
• Emerging evidence suggests that prenatal and childhood DHA intake can have
beneficial effects on memory processing as children develop. Selection of
seafood products with low levels of neurotoxic pollutants is necessary for this
association. 74
• Fish intake (high in Omega-‐3s) has been positively linked to the cognitive and
academic performance of school-‐aged students. 75, 76
• Improvements in processing speed, visual-‐motor coordination, perceptual
integration, attention and executive function are evident with Omega-‐3
supplementation.77
• Approximately 4 of every 100 children in Australia have ADHD. Significant co-‐
morbidities of ADHD include mood and impulsivity disorders, oppositional
defiance disorder, obsessive-‐compulsive disorder and depression. In 60% of
cases of childhood ADHD, symptoms or difficulties remain throughout life. 59, 60
• There is emerging evidence for the role of seafood or fish oil supplements in the
management of attention disorders such as ADHD. 60-‐66 Diets high in Omega-‐3s
have resulted in a marked improvement in the behaviours of children with
ADHD.59, 60, 68 78 Therefore, children with ADHD should be encouraged to
consume Omega-‐3 PUFA. 67
• Recent data indicated that 26% of Australians aged 16-‐24 years had a mental
health disorder in the 12 months prior to the survey. 79 Adolescents may have
additional compounding concerns of: poor diet (e.g. processed meats, sugars,
26
fats, and salt); adverse socioeconomic conditions; increased screen time; risky
health behaviours; alcohol misuse; smoking and risky sexual behaviours. 5
• Strong evidence supports the benefits of a diet high in Omega-‐3s as an adjunct
therapy for people with depression, behavioural problems, mood and
impulsivity disorders. 80 Research has shown that low levels of red blood cell
DHA have a positive correlation with clinical depression scores in children with
juvenile bipolar depression. 81
• Emerging evidence supports adequate levels of Omega-‐3s in early development
and into adulthood to aid in the prevention of aggression and hostility. 5
• A 12 week dietary intervention high in Omega-‐3’s and low in Omega-‐6’s
significantly reduced the number of headache days per month and the headache
hours per day in people who previously suffered from daily headaches. 82
• Cognitive ability is influenced by the ratio of Omega3’s to Omega-‐6’s in children.
Higher levels of Omega-‐3s are predictive of significantly improved cognitive
development. 83
• DHA is highly concentrated in the brain. DHA and EPA support the composition
and function of the central nervous system. Animal studies have demonstrated
loss of function of the brain and eye with DHA depletion. 84
• The risk of poor language development outcomes is increased with lower levels
of DHA.85
27
3.7 Cancer -‐ Summary of evidence
High-‐level evidence supports fish consumption as protective in reducing the risk and
mortality rate associated with certain nutrition related cancers (particularly in
males). Specifically, evidence supports the association of a balanced diet high in
Omega-‐3s with a significant reduction in the risk of ovarian, prostate, lung, breast
and colorectal cancers. Emerging evidence supports the consumption of Omega-‐3s
in reducing the incidence of pancreatic and bladder cancer plus colorectal
adenomas. Inflammation associated with existing lung cancer can be reduced with
regular ingestion of Omega-‐3s. Furthermore, at least 2 grams of EPA per day helps to
maintain weight and muscle mass during chemotherapy.
Women are particularly susceptible to bone loss following menopause. There is an
additional risk of bone loss for those women who are both menopausal and breast
cancer survivors due to the effects of common cancer treatments. One study has
found that supplementation of 4g/day of Omega-‐3s for 3 months was effective in
reducing the amount of bone loss in these women. It is important to note that
supplementation for menopausal women (including those who have had cancers)
should be part of an overall treatment program overseen by a medical practitioner.
Cancer -‐ Main outcomes of studies
• High fish intake has been associated with significant reductions in the risk of
some nutrition related cancers, particularly ovarian and colorectal cancer. 86-‐91
• High-‐level evidence supports fish consumption as protective in reducing the risk
of and mortality rates of cancer in males, particularly prostate and lung cancers. 92-‐97
• There is increasing evidence demonstrating an association between Omega-‐3
PUFA intake and a decreased risk of breast cancer. 90
• Epidemiological studies assessing the benefits of fish and seafood consumption
associated with the risk of lung, prostate, breast, colorectal, ovarian, pancreatic,
28
skin (basal cell carcinoma), stomach and non-‐Hodgkin lymphoma show
promising results.61, 92, 94, 98-‐102
• Although further research is necessary, emerging evidence shows benefits from
Omega-‐3 PUFA provision during the treatment of breast and colorectal cancer. 102-‐106 Emerging evidence also supports the ingestion of pharmaceutical Omega-‐
3 fish oil emulsion post gastric tumour resection to reduce damage caused by
inflammation of the liver.107
• Emerging evidence links high intakes of Omega-‐3 PUFA (particularly DHA) and
non-‐fried fish to a lower incidence of pancreatic cancer. 108 Evidence from
cellular models indicates that DHA may affect the metastatic potential of
bladder and pancreatic cancer cells. 109
• Adenomatous and hyperplastic polyps are often precursors for colorectal cancer.
High intakes of Omega-‐3 PUFA have been associated with a reduced risk of
colorectal adenomas in women. 110
• Intake of Omega-‐3 PUFA has been shown to increase the quality of life and
functional status in patients with non-‐small cell lung cancer undergoing
multimodality treatment. 111 Supplementation of ≥ 2 g/day of EPA provided
benefits in maintaining weight and muscle mass during chemotherapy
treatment. Positive associations were also observed between increased
concentrations of EPA and rates of muscle gain. 112, 113
• Women who are both postmenopausal and breast cancer survivors are at risk of
accelerated bone loss due to common cancer treatments. Short-‐term, high dose
of fish oil (4g per day for 3 months) can reduce bone resorption in this
population. 114 (Supplementation should be part of an overall treatment regime
developed and administered by a medical practitioner for these women).
29
3.8 Cardiovascular Diseases -‐ Summary of evidence
The evidence is clear – fish and Omega-‐3s are beneficial to heart and cardiovascular
health. As little as one serve of oily fish per week can reduce the risk of coronary
heart disease and stroke. Two or more serves per week provides increased
protection against all CVDs. Eating fish regularly significantly reduces the risk of
heart attack. This is thought to be due, in part, to the impact that Omega-‐3s have in
reducing triglyceride (TG) levels in the blood, which is beneficial to heart health. If
there is no previous history of heart disease, this reduced risk may be as much as
35% (compared with those eating no fish). The reasons for this reduced risk include
decreased cholesterol levels, lower blood pressure, lower resting heart rate, and
softer artery walls. To gain the maximum benefits from eating fish it is best to either
pan fry fillets or whole fish in a small amount of oil, or bake fish. (Remember, by
deep-‐frying fish in oil, most of the health benefit is negated.) Oily fish such as
salmon, mackerel and sardines provide the highest benefit.
Cardiovascular Diseases -‐ Main outcomes of studies
• Fish and Omega-‐3 intake is beneficial to heart 115-‐121 and cardiovascular health. 1,
122-‐129 One serve of fish per week reduces the risk of CHD and stroke.130, 131 Two
or more serves of fish each week provides increased protection against all CVDs. 132-‐134
• Supplementation of 1 g/day of Omega-‐3s has beneficial effects on a number of
associated disease factors in patients with CHD. 135 Some of these favourable
effects appear to act in a dose-‐dependent manner to supplementation. 136
• Consumption of Omega-‐3s is associated with a reduced risk of CVD, cardiac
events (heart attack) and mortality. 137-‐142 For people with pre-‐existing coronary
disease, increasing fish consumption or fish-‐oil supplementation is associated
with reduced coronary mortality and sudden death. 142, 143
• High-‐level evidence supports supplementation of Omega-‐3s for at least six
months in people at high risk of CVD will decrease the risk of all types of cardiac
events by 10%, cardiac death by 9% and coronary event by 18%. 144
30
• For subjects previously free of known CHD, consumption of ≥ 250 mg of Omega-‐
3s daily is associated with a reduced risk of sudden cardiac death (35.1%) and
total fatal coronary events (16.6%). 145
• Regular consumption of Omega-‐3s may decrease cholesterol levels. 14676-‐78 79
Some studies suggest that supplementation of Omega-‐3s together with other
cholesterol lowering methods (statins and phytosterols) have supplementary
effects. 126, 143, 147, 148 Other researchers dispute the benefits of combining
Omega-‐3s with statin therapy for reducing elevated cholesterol levels. 144
• High-‐level evidence demonstrates that supplementation of 1800 mg of EPA per
day is effective at lowering the risk of a major coronary event in people with
high cholesterol levels. 149
• Supplementation of 4 g/d of Omega-‐3s has been shown to significantly decrease
elevated serum TG concentrations. 10, 126, 143 Similar results have been found in
healthy men and women with fish and/or Omega-‐3s consumption, with
beneficial effects on TG levels. 13, 150, 151
• Regular consumption of fish and Omega-‐3s found in fish and seafood can lower
blood pressure in a dose dependent manner. 150, 152, 153 Supplementation of 3g of
Omega-‐3s per day can significantly lower elevated blood pressure levels. 153
• Supplementation of Omega-‐3s has positive effects on blood vessels showing a
significant reduction in arterial stiffness. 154
• High-‐level evidence shows that intake of Omega-‐3s has favourable, dose
dependent effects on heart rate. 136, 155
• The risk of cerebrovascular disease is reduced with high levels of fish
consumption. 88 This includes a reduced risk of death from stroke and all-‐cause
ischemic heart disease (blockage of the arteries) in both men and women.
Consumption of one serve of fish per week has shown to significantly reduce the
incidence of ischemic stroke. 16 118, 141, 156
• The effects of EPA and DHA supplementation appear to have gender specific
responses on thrombotic risk factors. 157
31
• A high level of plasma fibrinogen is a known risk factor for both CHD and stroke.
Emerging observational evidence indicates that high serum concentrations of
Omega-‐3s may decrease plasma fibrinogen levels. 158
• Research has found that individuals who consume large amounts of fish have a
15% lower risk of heart failure than those who consume very little fish. 10, 159
• High-‐level evidence shows that Omega-‐3 supplementation has been associated
with a 34% decrease in the odds of developing postoperative atrial fibrillation. 160
• Fish and/or Omega-‐3s consumption is associated with lower levels of
inflammatory markers indicating a lower risk of CHD 151, 161, 162 Consumption of
0.6 g/day of Omega-‐3s appears to be the optimal level for the maximal
reduction of inflammatory level markers. 161
• People with human immunodeficiency virus (HIV) often develop dyslipidemia
(abnormal amounts of lipoproteins) as a result of infections and treatment. This
puts these patients at higher risk of CVD. Studies have shown that Omega-‐3
supplementation in conjunction with standard lipid lowering treatments
enhances the reduction of serum TG levels in HIV patients. 163
• Consuming Omega-‐3s in place of saturated fatty acids (SFA) reduces CHD risk.
When these PUFA are in the form of Omega-‐6s these beneficial effects are not
observed. 164 Similarly, the shorter chain Omega-‐3 ALA does not exert the same
cardiovascular health benefits as the longer chained EPA and DHA 165
• Consumption of fish, as part of the Mediterranean diet, has been associated with
a lower risk of vascular events. 166
• The National Heart Foundation of Australia recommends that Australians
consume 500 mg/d of combined EPA and DHA to lower their risk of CHD and
1000 mg/d for adults with existing CHD. For people with elevated TGs, a starting
dose of 1000 mg of Omega-‐3s daily is recommended increasing to 4000 mg/d if
appropriate. 167 (Higher levels of supplementation should be part of an overall
32
treatment and management plan developed and administered by a medical
practitioner.)
• The benefits of eating fish can depend on the way it is prepared for
consumption. 168 Broiled or baked fish maintains the health benefits better than
deep fried fish; with fried fish showing no association with a lowered risk of
ischemic heart disease. 16 Consumption of non-‐fried fish containing Omega-‐3s is
associated with a lower odds ratio of atherosclerosis. 169, 170
• Consumers of fish oil supplements and EPA/DHA enriched concentrates need to
consider accuracy of content claims, oxidative stability, negligible levels of
environmental contaminants and the appropriate accompanying presence of
physiological antioxidants, when purchasing these products. 171
• Despite knowledge of the benefits of fish oil and favourable attitudes toward
nutritional therapy, family physicians infrequently recommend fish oils to CVD
patients. 172
• High levels of Omega-‐3s within the red blood cells of patients with peripheral
artery disease are associated with lower levels of inflammation. 173
• The anti-‐inflammatory properties of Omega-‐3s may have a beneficial effect on
chronic chagasic cardiomyopathy, an inflammatory disease of the heart. 174
• Lower levels of Omega-‐3s in the blood were associated with higher levels of
atrial fibrillation in patients with chronic heart failure. 175
• A diet high in Omega-‐3s reduces TG levels, which is beneficial to heart health
(reduces risk of CVD). 176 177
• Prescription-‐only EPA supplementation of 2g/day was effective in lowering very
high level of TGs. This has implications for those at high risk of diabetes and
CVD. 178
• A combination of statins with Omega-‐3 supplementation reduced the risk of
subsequent adverse cardiovascular outcomes following myocardial infarction. 179
33
• Strong evidence supports a high dose Omega-‐3 supplementation (at least
1g/day) as a protective measure against cardiac death, sudden death and
myocardial infarction in patients with existing CVD. 180
• Use of Omega-‐3s following adverse cardiac events in a hospital setting has
proven an effective adjunct therapy in reducing cardiac arrhythmic events.181
• Some large studies have reported little or no association between Omega-‐3s
and CVD risk. 182-‐184 However, many of these studies do not measure baseline
Omega-‐3 levels or other dietary and health factors that impact on Omega-‐3s in
the body. Other studies have used macro or self-‐reported measures which
reduced the accuracy of findings. There is a call for the uniform implementation
of standardised and valid measures of Omega-‐3s such as the Omega-‐3 Index.185
3.9 Cystic Fibrosis -‐ Summary of evidence
Cystic fibrosis (CF) is a genetic condition mainly affecting the cells of the lungs,
pancreas, liver and digestive systems. There is strong evidence that the regular
consumption of Omega-‐3s in the management of CF can help to reduce
inflammation and mucus levels.
Cystic Fibrosis -‐ Main outcomes of studies
• High-‐level evidence suggests regular intake or supplementation of Omega-‐3s
can provide some anti-‐inflammatory benefits for people with CF with relatively
few adverse effects. 186, 187
34
3.10 Diabetes -‐ Summary of evidence
Seafood is an excellent source of lean protein. It is also low in saturated fat and high
in important Omega-‐3s. There is substantial evidence that Omega-‐3s play a key anti-‐
inflammatory role in the body. Omega-‐3s also assist in the prevention and
management of CVD, a condition many diabetics are highly susceptible to.
Seafood is second only to the sun as a source of Vitamin D. People with diabetes are
more prone to deficiency of this vitamin, and can benefit from regular consumption
of seafood as a part of a healthy diet. Evidence suggests that men should aim to
consume 600mg of Omega-‐3s each day and women 500mg. Generally this equates
to 2-‐3 serves (100g) of seafood each week. Seafood high in Omega-‐3s are sardines
(canned or fresh), Atlantic salmon (canned or fresh), rainbow trout, bream, oysters,
mussels and mullet.
Diabetes is often associated with high levels of TGs and general inflammation within
the body. At least 2 g/day of Omega-‐3s can reduce TG levels in most people with
nutrition-‐related diabetes. For those with uncontrolled diabetes, 4 g/day of ethyl
EPA (a prescription only medication) can assist in the control of both high levels of
triglycerides and inflammation.
Recent advances in diabetes research have shown a positive link between the
genetic makeup of individuals and the level of benefit that can be gained from a diet
high in Omega-‐3s. Further research in this area could lead to tailored Omega-‐3
supplementation that will maximize individual health benefits.
Diabetes -‐ Main outcomes of studies
• Regular fish consumption should be part of a healthy diet for diabetic
management. 188, 189
• A weak positive association has been observed between fish and Omega-‐3 FA
intake, and the risk of developing type 2 diabetes mellitus (T2DM). 190
35
• Physical activity, a body mass index (BMI) less than 25, and a Mediterranean diet
high in fruit, vegetables, carbohydrates with a low glycaemic index (GI) or high
fibre, and 30-‐35% total fat (high in monounsaturated fatty acids and Omega-‐3s,
and low in saturated fat) appears to be preventative against T2DM. 191, 192
Adherence to a Mediterranean diet pattern has been associated with a 12%
reduction in the likelihood of developing T2DM. 193
• Regular fish consumption by women with T2DM was associated with a lower
incidence of both CHD and total mortality. 188
• Albuminuria (albumin in the urine) is an indicator of kidney damage. Research
has found that greater fish consumption was associated with a lower risk of
macro albuminuria in people with diabetes. 194
• High-‐level evidence demonstrates that Omega-‐3 PUFA supplementation in
people with T2DM can significantly decrease TGs and very-‐low density
lipoprotein (VLDL) cholesterol levels. 195 However, in some cases Omega-‐3 PUFA
supplementation increased low-‐density lipoprotein (LDL) cholesterol levels. 196,
197 This may be a factor of the macro measurements used therefore this finding
requires further investigation.
• Fish oil can impair glucose tolerance in individuals with high phospholipid
Omega-‐6: Omega-‐3 ratios. Fish oil supplementation for these individuals should
either be avoided or accompanied by decreases in Omega-‐6 dietary intakes. 198
• A large cohort study found that higher consumption of total, white or oily fish
was associated with a 25% reduction in the risk of developing T2DM. 199
• At least 2 g/day of DHA+EPA significantly reduced triglycerides levels. 177 176
• 4 g/day of ethyl EPA (prescription medication) significantly reduced triglyceride
levels and inflammation in patients with diabetes. It was particularly beneficial
to patients with uncontrolled diabetes. 200
• Oily fish high in Omega-‐3s offers significant protection against T2DM. 201
• Research has shown a clear positive link between the influence of genetic
variation on fasting glucose and fasting insulin levels in response to Omega-‐3
36
supplementation. This has implications for the development of tailored
treatment of diabetes based on metabolic differences. Further research should
focus on the influence of genes on glucose and insulin responses in the presence
of Omega-‐3s. 202
3.11 Kidney Disease -‐ Summary of evidence
There is evidence of a connection between the consumption of Omega-‐3s, and
better kidney health. A diet high in seafood helps to maintain a healthy weight,
which in turn, helps to regulate blood pressure and blood glucose, both implicated in
kidney disease. As kidney disease is often associated with CVD, it appears that the
consumption of Omega-‐3s may be beneficial for those with end-‐stage kidney
disease.
Kidney Disease -‐ Main outcomes of studies
• Emerging evidence has linked Omega-‐3 PUFA and fish intakes with the
maintenance of kidney health. 203
• Patients with kidney disease are at high risk of developing CVD. Promising
evidence suggests that the cardio-‐protective role of Omega-‐3 PUFA on CVD risk
factors and disease factors, may be beneficial for patients with end stage kidney
disease. 204, 205
• Omega-‐3 PUFA supplementation has beneficial effects on insulin resistance 206
and inflammatory markers in patients undergoing haemodialysis. 162
• Omega-‐3 supplementation of 3g/day in patients with end stage renal disease
reduced their risk of CVD. 207
• A diet high in Omega-‐3s reduced systemic inflammation and improved lipid
levels in renal transplant patients. 207, 208
37
3.12 Liver Disease -‐ Summary of evidence
A balanced diet high in seafood offers real benefits in the prevention and
management of diabetes and obesity, both primary risk factors for liver disease. The
consumption of seafood as part of a health diet may help to prevent fatty liver
disease (hepatic steatosis).
Liver Disease -‐ Main outcomes of studies
• Emerging evidence suggests that Omega-‐3 PUFAs may be beneficial for the
prevention or management of non-‐alcoholic fatty liver disease. 209 210 211
3.13 Maternal and Child Health -‐ Summary of evidence
As expectant mothers know, good nutrition is vitally important for their own health
during pregnancy and their baby’s development. Nutrition is particularly important
for the optimal development of the brain and central nervous system and Omega-‐3s
play a very important role in both. In short, Omega-‐3s are essential to brain
development during pregnancy, particularly DHA – the most important Omega-‐3
fatty acid for brain development. (These benefits continue after a child is born.)
Regular consumption of fish during pregnancy has been associated with decreased
rates of premature delivery, increased birth weight and lower hypertension, all
factors that improve long-‐term outcomes for infants. Some studies have shown that
Omega-‐3s present in the breast milk of mothers who eat fish are associated with
(healthy) infant weight gain, height, and BMI. Others have found that a mother’s fish
consumption is linked with higher child development scores, improved language
skills and sound visual development.
Pregnancy can be a time of heightened anxiety for expectant mothers. As noted, a
balanced diet rich in Omega-‐3s is essential for good health but has the additional
benefit of reducing high levels of anxiety during pregnancy.
38
Maternal and child health -‐ Main outcomes of studies
• Evidence supports a diet high in Omega-‐3s as being beneficial to the health of
women throughout the lifespan.212 This is most important during pregnancy and
breastfeeding as maternal nutrition is important to development of the foetal
and infant brain. 213
• Seafood is an excellent source of Omega-‐3s, which are essential for optimal
foetal neural development. 50, 214, 215 Positive associations exist between long
chain Omega-‐3 PUFA supplementation and the neurodevelopment of the
offspring. 50, 216, 217 The ideal dose of Omega-‐3 PUFA, composition and ratio of
EPA:DHA to maximise child development requires further investigation.218
• High levels of fish intake during pregnancy have been associated with longer
gestation, 217 increased birth weight and lower rates of hypertension during
pregnancy. 50, 219, 220, 221, 222, 223
• Observations show that the total amount of PUFA in a mother’s breast milk is
positively associated with weight gain, height and BMI in premature infants. 224
• Omega-‐3 PUFA intakes during pregnancy may be beneficial on a number of
infant birth outcomes. 225
• Prenatal long chain PUFA availability is influenced by maternal diet. Associations
have been made between prenatal availability of long chain PUFA and the motor
function of children at 7 years of age. 226
• Consumption of two salmon (high in Omega-‐3s) meals per week during
pregnancy lowered inflammatory markers in offspring, which is associated with a
decreased risk of CVD. 227
• Although further research is required, EPA and DHA supplementation may be
beneficial for women with perinatal depression. 66, 228 A small cohort showed
that pregnant women with lower levels of Omega-‐3 PUFA were six times more
likely to have antenatal depression than women with higher levels. 229
39
• Research has shown that the dietary patterns of girls and boys should be
considered separately when assessing their intake of Omega-‐3s and thus in the
development of targetted dietary interventions. 230
• Greater maternal fish consumption has been linked to higher child
developmental scores at 18 months, improved performance in language and
visual motor skills 223, 222 and visual development. 73
• Deficit of DHA during pregnancy impacts adversely on neural development and
gene expression. Adequate maternal intake of DHA is essential to the central
nervous system development of infants. 85
• Although cause and effect has not been established, a diet rich in Omega-‐3s can
reduce high anxiety levels during pregnancy. 231
• There are beneficial effects on child development of a maternal seafood intake
of more than 340 g per week. This suggests that advice to limit seafood
consumption could actually be detrimental. The risks from loss of nutrients to
the foetus were greater than the risk of harm from exposure to trace
contaminants in 340 g seafood eaten weekly.214, 232
• Fish and seafood intake guidelines for women who are pregnant, may become
pregnant or are breastfeeding need to be specific about fish species to ensure
adequate intakes of Omega-‐3 PUFA and minimal intake of methylmercury. 233 It
appears that some pregnant women have limited knowledge of the benefits of
Omega-‐3 PUFA intake during pregnancy. 234
• Some fish and seafood are potential sources of pollutants such as methylmercury
that may adversely affect pregnancy outcomes. Thus, advising pregnant women
about fish consumption requires consideration of potential risks as well as
benefits.219, 235, 236 There are national guidelines that seek to minimise any risk of
consumption of fish and seafood during pregnancy. These guidelines note the
health benefits far outweigh the minimal risk. However, not enough women of
childbearing age are consuming adequate fish for health benefits. 237
40
3.14 Mental Health and Behavioural Conditions -‐ Summary of evidence
There is an association between the consumption of Omega-‐3s from fish and mental
health and/or behavioural issues. Frequent seafood consumption is associated with
lower levels of depression. This is thought to be due to the ingestion of Omega-‐3s,
iodine, selenium, zinc and Vitamin B12 – all found in seafood and often deficient in
those with depression. Most studies support a balanced diet high in oily fish as a
complimentary therapy for the prevention and management of mental health and
behavioural conditions. Omega-‐3s are essential to the optimal function of the brain
therefore oily fish should be included in diets for good mental health. Children and
adults with behavioural issues often benefit from the additional fish oil supplements
in their diet as they provide high doses of DHA, the type of Omega-‐3s that aids brain
function.
In general seafood is good for mental health. People with a wide range of mental
health conditions (e.g. depression, anxiety and bipolar disorder) who eat fish
regularly, say it made them feel better and helped them manage their condition.
Anxiety and depression are two of the most common mental health conditions
facing Australians today. There is good evidence linking a balanced diet high in
Omega-‐3s with reduced depressive symptoms in both men and women. There is also
evidence supporting the intake of at least 1.2 g/day of Omega-‐3s to reduce
impulsivity, anger outbursts and other symptoms associated with borderline
personality disorder, particularly in adolescents. There is good evidence supporting a
diet high in oily fish (with or without fish oil supplements) for children and adults
with ADHD.
It is important to note that, for these conditions, nutritional therapies should be part
of a tailored treatment program administered by an appropriately qualified medical
practitioner.
41
Mental Health and Behavioural Conditions -‐ Main outcomes of studies
• An Australian survey found that approximately 20% of Australians aged 16 to 85
years reported a mental health disorder in the previous 12 months. 79, 238
• Fish consumption is associated with a significantly higher self-‐reported mental
health status. 239, 240
• A mean daily intake of 10 g of seafood is linked to a lower prevalence of poor
cognitive performance. 241
• Higher dietary intake of Omega-‐3s offers some protection against depression. 238
• Worldwide, there are significant negative correlations between fish consumption
and depression (including post-‐partum), bipolar disorder and suicidal ideation.239,
242-‐244
• Emerging evidence suggests there are benefits of Omega-‐3 PUFA
supplementation on depressive symptoms in people with bipolar disorder. 235, 245,
246
• Adequate fish intake has a negative association with depressed mood, risk of
recurrent depressive episodes and depressive symptoms. 120, 247, 248
• Emerging evidence shows supplementation of 1gm of Omega-‐3 PUFA a day in
children with major depression significantly reduces depression scores. 249
• Omega-‐3 has a role in reducing impulsivity, psychiatric symptoms and outburst of
anger in the treatment of borderline personality disorder. Nutritional strategies
focussing on at least 1.2 g/day of Omega-‐3s should be explored as a minimally
invasive treatment for adolescents with borderline personality disorders. 250, 251
• There is good evidence linking Omega-‐3 intake and reduced depressive
symptoms in both men and women. 252, 253
• A growing body of evidence suggests a protective effect of Omega-‐3s against
dementia.254, 255, 255 Intake of at least one fish serve per week reduces the risk of
Alzheimer’s disease. 256-‐258
42
• Changes to the traditional Western diets to include adequate levels of Omega-‐3s
should be considered when developing or modifying food, health and dietary
policies. 259
3.15 Metabolic Syndrome -‐ Summary of evidence
Metabolic syndrome refers to a condition where multiple risk factors for both CVD
and T2DM occur together. The main risk factors are: abdominal fat; high blood
pressure; low levels of ‘good’ cholesterol (high density lipoproteins -‐ HDL); high
levels of ‘bad’ cholesterol (low density lipoproteins -‐ LDL); high levels of TGs; insulin
resistance; physical inactivity and cigarette smoking. As seafood is beneficial in the
prevention and management of both CVD and T2DM, there is good reason to believe
that the consumption of seafood (particularly those high in Omega-‐3s) would be
beneficial in the prevention, management and treatment of metabolic syndrome.
Some studies have shown that a Mediterranean diet pattern, including fish, is
associated with just such positive outcomes. Significant health benefits in adults
were gained with supplementation of 2 g/day of Omega-‐3s.
Metabolic Syndrome -‐ Main outcomes of studies
• Metabolic syndrome is a term used to describe a cluster of risk factors
(abdominal obesity, dyslipidaemia, hypertension and insulin resistance)
observed in an individual. With known beneficial effects of Omega-‐3s on some
of these risk factors, it is likely they are beneficial in the management and
treatment of metabolic syndrome. 260
• Supplementation of >1 g a day of Omega-‐3s produced significant reductions in
the serum triglycerides of patients with metabolic syndrome. 261
• Adherence to a Mediterranean diet pattern (which includes fish) is associated
with favourable effects on the components of metabolic syndrome. 262
43
• Improvements in endothelial function and arterial stiffness were evident in
adults with metabolic syndrome after supplementation with 2 g/day of Omega-‐
3s. Reduction in inflammation was also evident. 263
• DHA may help to prevent metabolic syndrome based on its impact on
inflammation and insulin, however further studies are required to establish
adequate doses required to reduce risk. 264
3.16 Osteoporosis -‐ Summary of evidence
A group of conditions affecting the muscles and bones of the body are known as
musculoskeletal conditions. One of the most common types of musculoskeletal
problems is osteoporosis, an extremely painful and debilitating condition resulting in
an increased risk of bone fractures. Common symptoms are joint pain and
inflammation, stiffness, disability and deformity. Calcium and vitamin D, key
ingredients in seafood, aid in the prevention and management of osteoporosis.
Eating fish from an early age helps to lay down strong bones. Continual consumption
throughout life maintains bone health with some evidence that Omega-‐3s reduce
age-‐related bone and muscle loss.
Women are particularly susceptible to bone loss following menopause. There is an
additional risk of bone loss in women who are both menopausal and breast cancer
survivors due, in part, to the effects of common cancer treatments. One study has
found that supplementation of 4g/day of Omega-‐3s for three months was effective
in reducing the amount of bone loss in these women. It is important to note that
supplementation for this group of women should be part of an overall treatment
program overseen by a medical practitioner.
44
Osteoporosis -‐ Main outcomes of studies
• Evidence shows that fish intake is beneficial in the management of inflammatory
diseases. 1, 34
• A number of molecular mechanisms demonstrating the anti-‐inflammatory effects
of Omega-‐3 PUFA have been proposed. 35
• Adequate levels of Omega-‐3s are important for appropriate immune system
responses. 36
• Dietary intakes of Omega-‐3s are associated with lower levels of inflammation.265
Supplementation of 1.25 g/day of Omega-‐3 PUFA for four months significantly
lowered levels of inflammatory molecules. 37
• There is some evidence that Omega-‐3’s reduce age-‐related bone and muscle
loss. 266 Women who are both postmenopausal and breast cancer survivors are
at risk of accelerated bone loss due to common cancer treatments. Short-‐term,
high dose of fish oil (4g per day for 3 months) can reduce bone resorption in this
population. 114, 267
45
3.17 Overweight and Obesity -‐ Summary of evidence
Excessive weight is a risk factor for many medical and health conditions including
CVD, diabetes, musculoskeletal condition and some cancers. The more excess weight
a person has, the greater the risk of developing adverse health outcomes. Being
overweight or obese can also make it more difficult to prevent, or manage
conditions that may arise due to the additional stress that excess weight places on
the systems of the body.
Protein has a superior affect on satiety. Seafood is a great source of lean protein that
is readily absorbed by the body. This means you only need to eat a small amount
each day to get the protein producing energy you need. A serve of 100-‐150 g of
seafood is recommended, making it a very cost effective meal.
Seafood has a raft of essential nutrients that help the body and brain to function
effectively. It also helps reduce inflammation associated with obesity making
seafood the ideal choice for those wishing to become healthier. Inflammation is a
common problem associated with obesity. This type of inflammation spreads
throughout the whole body. A daily dose of Omega-‐3s (460mg EPA and 380mg DHA)
offers real benefits in reducing systemic inflammation associated with severe
obesity.
Overweight And Obesity -‐ Main outcomes of studies
• Obesity as a major risk factor for CVD, T2DM, and some musculoskeletal
conditions and certain nutrition-‐related cancers. 268 Suggestions have been
made that the development of some of these complications is tightly correlated
with the chronic low-‐grade adipose tissue and systemic inflammation associated
with obesity. Targeted interventions aimed at reducing weight through dietary
modifications have had limited success with the overweight and obese
population.269 However, recent research with severely obese, non-‐diabetic
subjects found that supplementation of 460 mg of EPA and 380 mg of DHA each
day improved adipose and systemic inflammation. 270
46
3.18 Possible Health Risks -‐ Summary of evidence
Pollutants: Like any natural food source, there is potential for the presence of dioxins
and other pollutants in seafood. Possible pollutants in seafood include mercury or
other heavy metals. However, many high-‐quality studies have concluded that the
level of these pollutants in fish and other seafood is generally very low, and that the
potential health benefits of fish consumption outweigh potential risks. Furthermore,
emerging evidence indicates that the when selenium is present, it helps to
counteract the effect of these pollutants. Further research is required to confirm this
association.
Researchers have built a good understanding of the mineral profile of various
species, meaning that it is possible to plan consumption to manage the small risk of
pollutants such as methylmercury. In practical terms, this means limiting
consumption of a small number of larger fish species. Food Standards Australia New
Zealand (FSANZ) has clear guidelines to assist with these decisions.
www.foodstandards.gov.au
Women who are pregnant, may become pregnant, or are breastfeeding should pay
particular attention to these recommendations, and infants up to six years should
limit their consumption of some species (see www.foodstandards.gov.au for
guidelines). However, fish should not be avoided altogether, as it is the single best
source of Omega-‐3s and other key nutrients that play an important role in foetal
neural development, the development of small children and delayed onset of
dementia as we age.
Supplementation: Fish oil supplements can provide benefits to those who either
don’t or can’t eat seafood. They are also helpful when larger doses of Omega-‐3s are
recommended to assist in the management of some chronic conditions (e.g.
arthritis). However, it is essential that only high quality supplements from reputable
sources are ingested, that they are stored according to instructions and are not
ingested past their used by date. Low quality, poorly handled ingredients prior to
encapsulation or fish oil past its’ used by date may pose a risk to human health.
47
Possible Health Risks -‐ Main outcomes of studies
• A balance of risk-‐benefit in relation to the consumption of fish and seafood is
recommended in the literature, taking into consideration meal size and
frequency of consumption. 137, 271
• Guidelines are to assist people to make informed choices about the types and
amount of seafood they ingest based on higher Omega-‐3 content and low
mercury concentrations. 272
• Levels of dioxins and other pollutants in fish are low, and potential carcinogenic
effects are outweighed by potential benefits of fish intake and should have little
impact on choices or consumption of seafood. 15
• Fish low in mercury and high in Omega-‐3s are recommended. 273, 274 Light tuna
has relatively low levels of mercury, and other fish, such as wild and farmed
salmon and shrimp, contain very low levels of mercury. 275
• Fish containing the highest amounts of Omega-‐3s in the United States (USA) are
farmed trout, farmed Atlantic salmon, Coho salmon, toothfish, Copper River
salmon and sockeye salmon.276
• Women of childbearing age should consult regional advisories for locally caught
freshwater fish. The benefits of modest fish intake, excepting a few selected
species, outweigh any potential risk. 15, 137
• Women who are pregnant, may become pregnant or are breastfeeding, as well
as very young infants should avoid fish that may contain mercury. Consumption
of fish and seafood should not, however, be avoided altogether as it is the
predominant source of Omega-‐3s, which are essential for optimum foetal neural
development. 214, 277
• Advances have made bio-‐monitoring a cost-‐effective public health tool for
helping federal, state and local health agencies develop optimal dietary
guidance.278
48
• Selenium appears to have a role in counteracting mercury toxicity. There are
suggestions that the selenium content in fish should be considered when
conducting mercury risk assessments. 277 These findings require further
investigation to confirm this association.
• Risk-‐benefit frameworks have been proposed as methods of determining optimal
intakes of fish/seafood. 274, 275, 279, 280
• The level of oxidation in fish oil supplements is an important factor in the
control of circulating lipoproteins. Highly oxidated products may be a risk to
human health. Manufacturers should test the level of oxidation in the
ingredients of supplements prior to encapsulation as a quality assurance
measure. 281
49
4.0 CONCLUSIONS
This report focussed on summarising the best evidence around the health benefits of
seafood for the prevention and management of chronic conditions. The benefits of
marine sourced Omega-‐3s for general, heart and brain health are well established
and generally well known. The strongest evidence is around the reduction of risk for
all cause mortality, coronary heart disease, diabetes, mental health disorders, and
nutrition related cancers. There is also strong evidence supporting the benefits of
regular consumption of seafood that are high in Omega-‐3s, for optimal brain
development and function, management of inflammatory conditions (such as
arthritis, asthma and hay fever) plus control of inflammation associated with lung
cancer and COPD, a common condition associated with impaired lung function.
Evidence is mounting in support of the regular consumption of seafood high in
Omega-‐3s in delaying the onset of Alzheimer’s Disease in susceptible people and
slowing the progress of the disease in those already affected. There is emerging
evidence supporting a seafood rich diet for people with cystic fibrosis; kidney
disease; liver disease and osteoporosis. Furthermore, eating seafood as the main
protein source can provide significant benefits in the dietary management of
overweight and obesity.
Less well recognised by the general population are the additional benefits that can
be gained from eating seafood (particularly oily fish) as a source of Omega-‐3s rather
than taking fish oil supplements. Seafood contains many nutrients (other than
Omega -‐3s) that help the body to perform efficiently and effectively. These include:
lean protein for cell repair and energy; vitamin D and calcium for bone and teeth
health; calcium for muscle, heart and nerve function; selenium to prevent cell
damage and promote healing and immune function; iodine (together with selenium)
to regulate thyroid function and metabolism; iron to help the blood carry oxygen to
cells and for energy production; and zinc to aid healing and for normal growth and
development
50
In summary, this systematic review of literature found that there is significant
evidence supporting the effectiveness of seafood (including fish) as an adjunct
therapy for the prevention and management of many common chronic conditions
affecting people today. Therefore, healthy eating and dietary guidelines that include
seafood as a major nutritional source, should be integral to health promotion
initiatives across the lifespan, not only to improve better short and long term health
outcomes, but also to reduce the significant health care costs associated with the
high prevalence of nutrition-‐related chronic conditions in Australia and around the
world.
51
5.0 REFERENCES 1. Ruxton C, Derbyshire E. Latest evidence on omega-‐3 fatty acids and health. Nutrition and Food
Science. 2009; 39(4):423-‐438. 2. Newton W, McManus A. Consumption of fish and Alzheimer’s Disease. Journal of Nutrition,
Health and Ageing. 2011; 8(3):551-‐552. 3. McManus A, Newton W. Seafood, nutrition and human health: A synopsis of the nutritional
benefits of consuming seafood Perth: Centre of Excellence Science, Seafood & Health, Curtin Health Innovation Research Institute, Curtin University. 2011.
4. McManus A, Fielder L, Newton W, White J. Health benefits of seafood for men. Journal of Men's Health. 2011; DOI:doi:10.1016/j.jomh.2011.04.004.
5. Hibbeln J, Nieminen L, Blasbalg T, Riggs J, Lands W. Healthy intakes of n 3 and n 6 fatty acids: estimations considering worldwide diversity. American Journal of Clinical Nutrition. 2006; 83S:1483S–93S.
6. Wang C, Harrris W, Chung M, Lichtenstein A, Balk E, Kupelnick B, et al. n-‐3 Fatty acids from fish or fish-‐oil supplements, but not α-‐linolenic acid, benefit cardiovascular disease outcomes in primary-‐ and secondary-‐prevention studies: a systematic review. American Journal of Clinical Nutrition. 2006; 84:5-‐17.
7. Tur JA, Bibiloni MM, Sureda A, Pons A. Dietary sources of omega 3 fatty acids: Public health risks and benefits. British Journal of Nutrition 2012; 107(S2):S23-‐S52.
8. Filion KB, El Khoury F, Bielinski M, Schiller I, Dendukuri N, Brophy JM. Omega-‐3 fatty acids in high-‐risk cardiovascular patients: A meta-‐analysis of randomized controlled trials. BMC Cardiovascular Disorders. 2010; 10:24.
9. Poole CD, Halcox JP, Jenkins-‐Jones S, Carr ESM, Schifflers MG, Ray KK, et al. Omega-‐3 fatty acids and mortality outcome in patients with and without Type 2 diabetes after myocardial infarction: A retrospective, matched-‐cohort study. Clinical Therapeutics. 2013; 35(1):40-‐51.
10. Saravanan P, Davidson N, Schmidt E, Calder P. Cardiovascular effects of marine omega-‐3 fatty acids. The Lancet. 2010; 376(9740):540-‐50. DOI:10.1136/ bmj.a2931.
11. Cannon D. From Fish oil to microalgae oil: A win-‐win shift for humans and our habitat. The Journal of Science and Healing. 2009; 5(5):299-‐303.
12. Zivkovic AM, Telis N, German JB, Hammock BD. Dietary omega-‐3 fatty acids aid in the modulation of inflammation and metabolic health. California Agriculture. 2011; 65(03):106.
13. Egert S, Kannenberg F, Somoza V, Erbersdobler H, Wahrburg U. Dietary [alpha]-‐linolenic acid, EPA, and DHA have differential effects on LDL fatty acid composition but similar effects on serum lipid profiles in normolipidemic humans. The Journal of Nutrition. 2009; 139(5):861-‐8.
14. Elvevoll E, Barstad H, Breimo E, Brox J, Eilersten K, Lund T, et al. Enhanced incorporation of n-‐3 fatty acids from fish compared with fish oils. Lipids. 2006; 41(12):1109.
15. Mozaffarian D, Rimm E. Fish intake, contaminants, and human health: Evaluating the risks and the benefits. Journal American Medical Association. 2006; 296(15):1885-‐99.
16. Mozaffarian D, Lemaitre R, Kuller L, Burke G, Tracy R, Siscovick D. Cardiac benefits of fish consumption may depend on the type of fish meal consumed: The Cardiovascular Health Study. Circulation. 2003; 107:1372-‐7.
17. Larsen R, Eilertsen KE, Elvevoll EO. Health benefits of marine foods and ingredients. Biotechnology Advances. 2011; 29(5):508.
18. Lordan S, Ross RP, Stanton C. Marine bioactives as functional food ingredients: Potential to reduce the incidence of chronic diseases. Marine Drugs. 2011; 9(6):1056-‐1100.
19. Riccioni G, D’orazio N, Franceschelli S, Speranza L, D’Orazio N. Marine Carotenoids and cardiovascular risk markers. Marine Drugs. 2011; 9(7):1166-‐1175.
20. Stonehouse W, Pauga MR, Kruger R, Thomson CD, Wong M, Kruger MC. Consumption of salmon v. salmon oil capsules: Effects on n-‐3 PUFA and selenium status. British Journal of Nutrition 2011; 106(8):1231-‐1239.
21. Hostenkamp G, Sorensen J. Are fish eaters healthier and do they consumer less health-‐care resources? Public Health Nutrition. 2009; 13(4):453-‐460.
52
22. Greiger J, McLeod C, Chan L, Miller M. Theoretical dietary modelling of Australian seafood species to meet long-‐chain omega 3 fatty acids dietary recommendations. Food & Nutrition Research. 2013; 57(20):737-‐747.
23. Jenson I, larsen R, Rustad T, Eilertsen K. Nutritional content and bioactive properties of wild and farmed cod (Gadus morhua L.) subjected to food preparation. Journal of Food Composition and Analysis. 2013; 31:212-‐216.
24. Papanikolaou Y, Brooks J, Reider C, Fulgoni V. U.S. adults are not meeting recommended levels for fish and omega-‐3 fatty acid intake: Results of an analysis using observational data from NHANES 2003-‐2008. Nutrition Journal. 2014; 13(31):1-‐6.
25. Gu Y, Nieves JW, Stern Y, Luchsinger JA, Scarmeas N. Food combination and Alzheimer Disease risk. Archives of Neurology. 2010; 67(6):E1-‐E8.
26. Arendash GW, Jensen MT, Salem Jr N, Hussein N, Cracchiolo J, Dickson A, et al. A diet high in omega-‐3 fatty acids does not improve or protect cognitive performance in Alzheimer's transgenic mice. Neuroscience. 2007; 149:286-‐302.
27. Söderberg M, Edlund C, Kristensson K, Dallner G. Fatty acid composition of brain phospholipids in aging and in Alzheimer's Disease. Lipids. 1991; 26(6):421.
28. Conner WE, Conner SL. The importance of fish and docosahexanoic acid in Alzheimer Disease. The American Journal of Clinical Nurtition. 2007; 85:929-‐930.
29. Lee L, Shahar S, Rajab N, Yusoff N, Jamal R, Then S. The role of long chain omega-‐3 polyunsaturated fatty acids in reducing lipid peroxidation among elderly patients with mild cognitive impairment: a case-‐control study. The Journal of Nutritional Biochemistry. 2012; (0) DOI:http://dx.doi.org/10.1016/j.jnutbio.2012.04.014.
30. Plourde M, Vohl M, Vandal M, Couture P, Lemieux S, Cunnane S, et al. Plasma n -‐3 fatty acid response to an n-‐3 fatty acid supplement is modulated by apoE ɛ4 but not by the common PPAR-‐α L162V polymorphism in men. British Journal of Nutrition. 2009; 102(8):1121-‐1124.
31. Cederholm T, Salem Jr N, Palmblad J. ω-‐3 fatty acid in the prevention of cognitive decline in humans. Advanced Nurtition. 2013; 4:672-‐676.
32. Konagai C, Yanagimoto K, Hayamizu K, Han L, Tsuji T, Koga Y. Effects of krill oil containing n-‐3 polyunsaturated fatty acids in phospholipid form on human brain function: A randomised controlled trial in healthy elderly volunteers. Clinical Interventions in Aging. 2013; 8:1247-‐1257.
33. Pottala J, Yaffe K, Robinson J, Espeland M, Wallace R, Harris W. Higher RBC EPA and DHA corresponds with larger total brain and hippocampal volumes. Neurology. 2014; 82(5):435-‐442.
34. McKellar G, Morrison E, McEntegart A, Hampson R, Tierney A, Mackle G, et al. A pilot study of a mediterranean-‐type diet intervention in female patients with rheumatoid arthritis living in areas of social deprivation in Glasgow. Annals of Rheumatoid Disease. 2007; 66:1239-‐1243.
35. Im D. Omega-‐3 fatty acids in anti-‐inflammation (pro-‐resolution) and GPCRs. Progress in lipid Research. 2012; 51(3):232-‐7.
36. Calder P. n-‐3 polyunsaturated fatty acids, inflammation and inflammatory diseases. American Journal of Clinical Nutrition. 2006; 83(6):S1505-‐S1519.
37. Kiecolt-‐Glaser J, Belury M, Andridge R, Malarkey W, Hwang B, Glaser R. Omega-‐3 supplementation lowers inflammation in healthy middle-‐aged and older adults: A randomized controlled trial. Brain, Behavior and Immunity. 2012; 26(6):988-‐995.
38. Pedersen M, Stripp C, Klarlund M, Olsen S, Tjønneland A, Frisch M. Diet and risk of rheumatoid arthritis in a prospective cohort. Journal of Rheumatology 2005; 32(7):1249-‐1252.
39. Kremer JM. n-‐3 fatty acid supplements in rheumatoid arthritis. American Journal Clinical Nutrition. 2007; 71(1):349S-‐351.
40. Gheita T, Kamel S, Helmy N, El-‐laithy N, Monir A. Omega-‐3 fatty acids in juvenile idiopathic arthritis: Effect on cytokines (IL-‐1 and TNF-‐[alpha]), disease activity and response criteria. Clinical Rheumatology. 2012; 31(2):363-‐6.
41. Caughey GE, James MJ, Proudman SM, Cleland LG. Fish oil supplementation increases the cyclooxygenase inhibitory activity of paracetamol in rheumatoid arthritis patients. Complimentary Therapies in Medicine. 2010; 18(3-‐4):171-‐4.
42. Miles EA, Calder PC. Influence of marine n-‐3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis. British Journal of Nutrition 2012; 107(S2):S171-‐S184.
53
43. Bahadori B, Uitz E, Thonhofer R, Trummer M, Pestemer-‐Lach I, McCarty M, et al. ω-‐3 fatty acids infusions as adjuvant therapy in rheumatoid arthritis. Journal of Parenteral and Enteral Nutrition. 2010; 34(2):151-‐155. DOI:10.1177/0148607109342130.
44. Gupta A, Mosharrof Hossain A, Hilalul Islam M. Role of omega-‐3 fatty acid supplementation with indomethacin in suppression of disease activity in rheumatoid arthritis. Bangladesh Medical Research Council Bulletin. 2009; 35:63-‐68..
45. Park Y, Lee A, Shim S-‐C, Lee JH, Choe J-‐Y, Ahn H, et al. Effect of n-‐3 polyunsaturated fatty acid supplementation in patients with rheumatoid arthritis: A 16-‐week randomized double-‐blind, placebo-‐controlled, parallel-‐design multicenterstudy in Korea. The Journal of Nutritional Biochemistry. 2013; 12:289-‐6. DOI:10.1016/j.jnutbio.2012.11.004.
46. Khider S, Majeed I, Taha M. Effects of omega-‐3 adjunct therapy to methotrexate on lipid profile in Iraqi patients with rhematoid arthrtis. Global Journal of Medical Research. 2013; 13(5):1-‐7.
47. Lundstrom S, Yang J, Branna J, Haeggstrom J, Hammock BD, et al. Lipid mediator serum profiles in asthmatics significantly shift following dietary supplementation with omega-‐3 fatty acids. Molecular Nutrional Food Research. 2013; 57:1378-‐1389.
48. Salam M, Li Y, Langholz B, Gilliland F. Maternal fish consumption during pregnancy and risk of early childhood asthma. Journal of Asthma. 2005; 42(6):513-‐518.
49. Oddy W, de Klerk N, Kendall G, Mihrshahi S, JK P. Ratio of omega-‐6 to omega-‐3 fatty acids and childhood asthma. Journal of Asthma. 2004; 41(3):319-‐326.
50. Larqué E, Gil-‐sánchez A, Prieto-‐sánchez M, Koletzko B, Gil-‐Sánchez A, Prieto-‐Sánchez M. Omega 3 fatty acids, gestation and pregnancy outcomes. British Journal of Nutrition. 2012; 107(S2):S77-‐S84.
51. Shek L, Chong M, Lim J, Shu E, Chong S. Role of dietary long-‐chain polyunsaturated fatty acids in infant allergies and respiratory diseases. Clinical & Developmental Immunology. 2012:730568.
52. Nafstad P, Nystad W, Magnus P. Asthma and allergic rhinitis at 4 years of age in relation to fish consumption in infancy. Journal of Asthma. 2003; 40(4):343-‐348.
53. Kiefte-‐de Jong J, de Vries J, Franco O, Jaddoe V, Hofman A, Raat H, et al. Fish consumption in infancy and asthma-‐like symptoms at preschool age. Pediatrics. 2012; 130(6):1060-‐1068. DOI:10.1542/peds.2012-‐0875.
54. Hodge L, Salome C, Peat J, Haby M, Xuan W, Woolcock A. Consumption of oily fish and childhood asthma risk. Medical Journal of Australia. 1996; 164:137-‐140.
55. Laerum B, Wentzel-‐Larsen T, Gulsvik A, Omenaas E, Gislason T, Jansonz C, et al. Relationship of fish and cod oil intake with adult asthma. Clinical and Experimental Allergy. 2007; 37:1616-‐23.
56. Li J, Xun P, Zamora D, Sood A, Liu K, Daviglus M, et al. Intakes of long-‐chain omega-‐3 (n-‐3) PUFAs and fish in relation to incidence of asthma among American young adults: The CARDIA study. The American Journal of Clinical Nutrition. 2013; 97(1):173-‐8.
57. Tartibian B, Maleki B, Abbasi A. The effects of omega-‐3 supplementation on pulmonary function of young wrestlers during intensive training. Journal of Science and Medicine in Sport. 2010; 13(2):281-‐6.
58. Chatzi L, Kogevinas M. Prenatal and childhood mediterranean diet and the development of asthma and allergies in children. Public Health Nutrition 2009; 12(9A):1629-‐1634.
59. Colter AL, Cutler C, Meckling KA. Fatty acid status and behavioural symptoms of attention deficit hyperactivity disorder in adolescents: A case-‐control study. Nutrition Journal. 2008; 7(8):1-‐11. DOI:10.1186/1475-‐2891-‐7-‐8.
60. Richardson A. Omega-‐3 fatty acids in ADHD and related neurodevelopmental disorders. International Review of Psychiatry. 2006; 18(2):155-‐172.
61. Burgess J, Stevens L, Zhang W, Peck L. Long-‐chain polyunsaturated fatty acids in children with attention-‐deficit hyperactivity disorder. American Journal of Clinical Nutrition. 2000; 71:327S -‐ 330S.
62. Hirayama S, Hamazaki T, Terasawa K. Effect of docosahexaenoic acid-‐containing food administration on symptoms of attention-‐deficit/hyperactivity disorder -‐ a placebo-‐controlled double-‐blind study. European Journal of Clinical Nutrition. 2004; 58:467 -‐ 473.
63. Sinn N, Bryan J. Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behaviour problems associated with child ADHD. Journal of Developmental Behaviour in Pediatrics. 2007; 28(2):82-‐91.
54
64. Young GS, Conquer JA, Thomas R. Effect of randomized supplementation with high dose olive, fax or fish oil on serum phospholipid fatty acid levels in adults with attention deficit hyperactivity disorder. Reproduction, Nutrition and Development. 2005; 45(5):549-‐558.
65. Johnson M, Mansson J, Ostlund S, Fransson G, Areskoug B, Hjalmarsson K, et al. Fatty acids in ADHD: Plasma profiles in a placebo-‐controlled study of omega 3/6 fatty acids in children and adolescents. ADHD Attention Deficit and Hyperactivity Disorders. 2012; 4(4):199.
66. Ramakrishnan U. Fatty acid status and maternal health. Maternal and Child Nutrition. 2011; 7(S2):99-‐111.
67. Ng K, Meyer B, Reece L, Sinn N. Dietary PUFA intakes in children with attention-‐deficit/hyperactivity disorder symptoms. British Journal of Nutrition. 2009; 102(11):1635-‐1641.
68. Montgomery P, Burtin J, Sewell R, Spreckelsen T, Richardson A. Low blood long chain omega-‐3 fatty acids in UK children are associated with poor cognitive performance and behaviour: A cross sectional analysis from the DOLAB study. PLoS ONE. 2013; 8(6):1-‐11.
69. Effat S, Mohomed N, Hussein H, Azzam H, Gouda A, Hassan H. ADHD symptoms: Relation to omega-‐3 serum levels before and after supplementation. European Journal of Psychiatry. 2013; 28:1.
70. Rahmawaty S, Charlton K, Lyons-‐Wall P, Meyer B. Dietary intake and food sources of EPA, DPA and DHA in Australian children. Lipids. 2013; 48:869-‐877.
71. Ramakrishnan U, Imhoff-‐Kunsch B, DiGirolamo AM. Role of docosahexaenoic acid in maternal and child mental health. American Journal of Clinical Nutrition. 2009; 89:958-‐62S.
72. Shannon S. Integrative approaches to pediatric mood disorders. Alternative Therapies. 2009; 15(5):48-‐53.
73. Jacques C, Levy E, Muckle G, Jacobson S, Bastien C, Dewailly É, et al. Long-‐term effects of prenatal omega-‐3 fatty acid intake on visual function in school-‐age children. Journal of Pediatrics. 2011; 158(1):73-‐80.e1.
74. Boucher O, Burden M, Muckle G, Saint-‐Amour D, Ayotte P, Dewailly E, et al. Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-‐3 fatty acid intake on memory function at school age. American Journal of Clinical Nutrition. 2011; 93(5):1025.
75. de Groot R, Ouwehand C, Jolles J. Eating the right amount of fish: Inverted U-‐shape association between fish consumption and cognitive performance and academic achievement in Dutch adolescents. Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA). 2012; 86(3):113-‐117.
76. Bauer I, Hughes M, Rowsell R, Cockerell R, Pipingas A, Crewther S, et al. Omega-‐3 supplementation improves cognition and modifies brain activation in young adults. Human Psychopharmacology. 2014; 29:133-‐144.
77. Portillo-‐Reyes V, Perez-‐Garcia M, Loya-‐Mendez Y. Clinical significance of neuropsychological improvements after supplementation with omega-‐3 in 8-‐12 year old malnourished Mexican children: A randomised double-‐blind placebo and treatment clinical trial. Research in Developmental Disabilities. 2014; 35:861-‐870.
78. Gow R, Hibbeln J. Omega-‐3 and treatment implications in attention deficit hyperactivity disorder (ADHD) and associated behavioural symptoms. Lipid Technology. 2014; 26(1):1-‐5.
79. Australian Bureau of Statistics. National survey of mental health: Summary of results, 2007, 2008. ABS Publication 4326.0; Canberra Australia.
80. Bodnar LM, Wisner KL. Nutrition and depression: Implications for improving mental health among childbearing-‐aged women. Biological Psychiatry. 2005; 58:679-‐685.
81. Clayton EH, Hanstock TL, Garg ML, Hazell PL. Long chain omega-‐3 polyunsaturated fatty acids in the treatment of psychiatric illnesses in children and adolescents. Acta Neuropsychiatrica. 2007; 19:92-‐103.
82. Ramsden C, Faurot K, Zamora D, Suchindran C, MacIntosh B, Gaylord S, et al. Targeted alteration of dietary n-‐3 and n-‐6 fatty acids for the treatment of chronic headaches: A randomized trial. Pain. 2013; 154:2441-‐2451.
83. Sheppard K, Cheatham C. Omega-‐6 to omega-‐3 fatty acid ratio and higher-‐order cognitive function in 7 to 9 y-‐olds: A cross-‐sectional study. American Journal of Clinical Nutrition. 2013; 98:659-‐667.
84. Salam Jr N. Docosahexaenoic acid (DHA) function and metabolism in the nervous system. iNFORM. 2013; 24(1):6-‐11.
85. Mulder K, King D, Innis S. Omega-‐3 fatty acid deficiency in infants before birth identified using a randomised trial of maternal DHA supplementation in pregnancy. PLoS ONE. 2014; 9(1):1-‐10.
55
86. Chan AT, Giovannucci EL. Primary prevention of colorectal cancer. Gastroenterology. 2010; 138(6):2029-‐2043.
87. Kolahdooz F, van der Pols J, Bain C, Marks G, Hughes M, Whiteman D, et al. Meat, fish and ovarian cancer risk: Results from 2 Australian case-‐control studies, a systematic review and meta-‐analysis. American Journal of Clinical Nutrition. 2010; 91(6):1752-‐63.
88. Lund E, Belshaw N, Elliott G, Johnson I. Recent advances in understanding the role of diet and obesity in the development of colorectal cancer. Proceedings of the Nutrition Society 2011; 70(2):194-‐204.
89. Wu M, Tsai Y, Hua K, Chang K, Kuo M, Lin M. Eicosapentaenoic acid and docosahexaenoic acid inhibit macrophage-‐induced gastric cancer cell migration by attenuating the expression of matrix metalloproteinase 10. The Journal of Nutritional Biochemistry. 2012; 23(11):1434-‐1439. DOI:http://dx.doi.org/10.1016/j.jnutbio.2011.09.004.
90. Gerber M. Omega-‐3 fatty acids and cancers: a systematic update review of epidemiological studies. The British Journal of Nutrition. 2012; 107(S2):S228-‐39.
91. Bell G, Kantor E, Lampe J, Kristal A, Heckbert S, White E. Intake of long-‐chain ω-‐3 fatty acids from diet and supplements in relation to mortality. American Journal of Epidemiology. 2014; 179(6):710-‐720.
92. Augustsson K, Michaud D, Rimm E, Leitzmann M, Stampfer M, Willett W, et al. A prospective study of intake of fish and marine fatty acids and prostate cancer. Cancer Epidemiology, Biomarkers & Prevention. 2003; 12:64-‐67.
93. Berquin I, Min Y, Wu R, Wu J, Perry D, Cline J, et al. Modulation of prostate cancer genetic risk by omega-‐3 and omega-‐6 fatty acids. Journal of Clinical Investigation. 2007; 117(7):1866-‐75.
94. Terry P, Thomas E, Wolk A. Intakes of fish and marine fatty acids and the risks of cancers of the breast and prostate and of other hormone-‐related cancers: A review of the epidemiological evidence. American Journal of Clinical Nutrition. 2003; 77:532-‐543.
95. Takezaki T, Inoue M, Kataoka H, Ikeda S, Yoshida M, Ohashi Y, et al. Diet and lung cancer risk from a 14-‐year population-‐based prospective study in Japan: With special reference to fish consumption. Nutrition and Cancer. 2003; 45(2):160-‐7. DOI:10.1207/S15327914NC4502_04.
96. Zhang J, Temme EHM, Kesteloot H. Fish consumption is inversely associated with male lung cancer mortality in countries with high levels of cigarette smoking or animal fat consumption. International Journal of Epidemiology. 2000; 29(615)
97. Zhang Y, Gao H, Hou A, Zhou Y. Effect of omega-‐3 fatty acid supplementation on cancer incidence, non-‐vascular death, and total mortality: A meta-‐analysis of randomized controlled trials. BMC Public Health. 2014; 14(204):1-‐12.
98. Fung T, Hu FB, Fuchs C, Giovannucci E, Hunter DJ, Stampfer MJ. Major dietary patterns and the risk of colorectal cancer in women. Archives of Internal Medicine. 2003; 163(3):309-‐314.
99. MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ. Effects of omega-‐3 fatty acids on cancer risk: A systematic review. Journal of the American Medical Association. 2006; 295(4):403-‐415.
100. Terry P, Lichtenstein P, Feychting M, Ahlbom A, Wolk A. Fatty fish consumption and risk of prostate cancer. The Lancet. 2001; 357(9270):1764.
101. Zhang J, Sasaki S, Amano K, Kesteloot H. Fish consumption and mortality from all causes, ischemic heart disease, and stroke: An ecological study. Preventive Medicine 1999; 28(5):520-‐9. DOI:S0091-‐7435(98)90472-‐8 [pii]10.1006/pmed.1998.0472.
102. Cockbain A, Toogood G, Hull M. Omega-‐3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer. Gut. 2012; 61(1):135.
103. Bougnoux P, Hajjaji N, Maheo K, Couet C, Chevalier S. Fatty acids and breast cancer: Sensitization to treatments and prevention of metastatic re-‐growth. Progress in Lipid Research. 2010; 49(1):76-‐86.
104. Chevalier S, Goupille C, Maheo K, Domingo I, Dussiau C, Renoux B, et al. Dietary docosahexaenoic acid proposed to sensitize breast tumors to locally delivered drug. Clinical Lipidology. 2010; 5(2):233.
105. Ravacci G, Brentani M, Tortelli Jr T, Torrinhas R, Saldanha T, Torres E, et al. Lipid raft disruption by docosahexaenoic acid induces apoptosis in transformed human mammary luminal epithelial cells harboring HER-‐2 overexpression. The Journal of Nutritional Biochemistry. 2013; 24(3):505-‐515. DOI:http://dx.doi.org/10.1016/j.jnutbio.2012.02.001.
56
106. Yang Y, Lu N, Chen D, Meng L, Zheng Y, Hui R. Effects of n-‐3 PUFA supplementation on plasma soluble adhesion molecules: A meta-‐analysis of randomized controlled trials. American Journal of Clinical Nutrition. 2012; 95(4):972.
107. Wei Z, Wang W, Chen J, Yang D, TYan R, Cai Q. A prospective randomised controlled study of ω-‐3 fish oil fat emulsion-‐based parenteral nutrition for patients following surgical resection of gastric tumors. Nutrition Journal. 2014; 13(25):1-‐6.
108. He K, Xun P, Brasky T, Gammon M, Stevens J, White E. Types of fish consumed and fish preparation methods in relation to pancreatic cancer incidence. American Journal of Epidemiology. 2013; 177(2):152.
109. D'Eliseo D, Manzi L, Merendino N, Velotti F. Docosahexaenoic acid inhibits invasion of human RT112 urinary bladder and PT45 pancreatic carcinoma cells via down-‐modulation of granzyme B expression. Journal of Nutritional Biochemistry. 2012; 23(5):452-‐457. DOI: http://dx.doi.org/ 10.1016/j.jnutbio.2011.01.010.
110. Murff H, Shrubsole M, Cai Q, Smalley W, Dai Q, Milne G, et al. Dietary intake of PUFAs and colorectal polyp risk. American Journal of Clinical Nutrition. 2012; 95(3):703-‐12.
111. van der Meij B, Langius J, Spreeuwenberg M, Slootmaker S, Paul M, Smit E, et al. Oral nutritional supplements containing n-‐3 polyunsaturated fatty acids affect quality of life and functional status in lung cancer patients during multimodality treatment: An RCT. European Journal of Clinical Nutrition. 2012; 66(3):399-‐404.
112. Murphy R, Mourtzakis M, Chu Q, Baracos V, Reiman T, Mazurak V. Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with non-‐small cell lung cancer receiving chemotherapy. Cancer. 2011; 117(8):1775-‐1782.
113. Murphy R, Mourtzakis M, Chu Q, Reiman T, Mazurak V. Skeletal muscle depletion is associated with reduced plasma (n-‐3) fatty acids in non-‐small cell lung cancer patients. Journal of Nutrition. 2010; 140(9):1602-‐6.
114. Hutchins-‐Wiese H, Picho K, Watkins B, Li Y, Tannenbaum S, Claffey K, et al. High-‐dose eicosapentaenoic acid and docosahexaenoic acid supplementation reduces bone resorption in postmenopausal breast cancer survivors on aromatase inhibitors: A pilot study. Nutrition and Cancer. 2014:1-‐9.
115. Mozaffarian D. JELIS, fish oil and cardiac events. The Lancet. 2007; 369(9567):1062-‐1063. 116. Mozaffarian D, Ascherio A, Hu F, Stampfer M, Willett W, Siscovick D, et al. Interplay between
different polyunsaturated fatty acids and risk of coronary heart disease in men. Circulation. 2005; 111(2):157-‐64.
117. Siscovick D, Raghunathan T, King I, Weinmann S, Bovbjerg V, Kushi L, et al. Dietary intake of long-‐chain n-‐3 polyunsaturated fatty acids and the risk of primary cardiac arrest. American Journal of Clinical Nutrition. 2000; 71(1 Suppl):208S-‐12S.
118. Zhang. J, Sasaki. S, Amano. K, Kesteloot. H. Fish consumption and mortality from all causes, ischemic health disease and stroke: An ecological study. Preventive Medicine. 1999; 28:520-‐529.
119. Calder P, Dangour A, Diekman C, Eilander A, Koletzko B, Meijer G, et al. Essential fats for future health. Proceedings of the 9th Unilever Nutrition Symposium, 26-‐27 May 2010. European Journal of Clinical Nutrition. 2010; 64(12):S1.
120. Hoffmire C, Block R, Thevenet-‐Morrison K, van Wijngaarden E. Association between omega-‐3 fatty acid supplementation and risk of major cardiovascular disease events: A systematic review and meta-‐analysis. Journal American Medical Association. 2012; 308(10):1024.
121. Jenkins D, Sievenpiper J, Pauly D, Kendall C, Mowat F. Are dietary recommendations for the use of fish oils sustainable? Canadian Medical Association Journal. 2009; 180(6):633.
122. Grenon S, Hughes-‐Fulford M, Rapp J, Conte M. Polyunsaturated fatty acids and peripheral artery disease. Vascular Medicine. 2012; 17(1):51-‐63.
123. Holub B. Docosahexaenoic acid (DHA) and cardiovascular disease risk factors. Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA). 2009; 81(2):199-‐204.
124. Holub BJ. Clinical nutrition: Omega-‐3 fatty acids in cardiovascular care. Journal of Applied Mathematics and Computing. 2002; 166(5):608-‐615.
125. Kromhout D, Yasuda S, Geleijnse J, Shimokawa H. Fish oil and omega-‐3 fatty acids in cardiovascular disease: Do they really work? European Heart Journal. 2012; 33(4):436-‐443.
126. Maki K, Dicklin M, Lawless A, Reeves M. Omega-‐3 fatty acids for the treatment of elevated triglycerides. Clinical lipidology. 2009; 4(4):425-‐437.
57
127. Mozaffarian D, Wu J. Omega-‐3 fatty acids and cardiovascular disease: Effects on risk factors, molecular pathways, and clinical events. Journal of the American College of Cardiology. 2011; 58(20):2047-‐2067.
128. Vrablík M, Prusíková M, Snejdrlová M, Zlatohlávek L. Omega-‐3 fatty acids and cardiovascular disease risk: Do we understand the relationship? Physiological Research. 2009; 58:S19-‐26. DOI:10.1136/ bmj.a2931.
129. Koh A, Pan A, Wang R, Odegaard A, Pereira M, Yuan J, et al. The association between dietary omega-‐3 fatty acids and cardiovascular death: The Singapore Chinese Health Study. European Journal of Preventive Cardiology. 2013; 0(0):1-‐9
130. Zheng J, Huang T, Yu Y, Hu X, Yang B, Li D. Fish consumption and CHD mortality: An updated meta-‐analysis of seventeen cohort studies. Public Health Nutrition. 2011; 15(4):725-‐737.
131. Campbell F, Dockinson H, Critchley J, Ford G, Bradburn M. A systematic review of fish oil supplements for the prevention and treatment of hypertension. European Journal of Preventive Cardiology. 2012; 20(1):107-‐120.
132. Albert C, Hennekens C, O'Donnell C, Ajani U, Carey V, Willett W, et al. Fish consumption and risk of sudden cardiac death. Journal of the American Medical Association. 1998; 279(1):23-‐8.
133. Ascherio A, Rimm E, Stampfer M, Giovannucci E, Willett W. Dietary intake of marine n-‐3 fatty acids, fish intake and the risk of coronary disease among men. New England Journal of Medicine. 1995; 332(15):977-‐82.
134. Chrysohoou C, Panagiotakos D, Pitsavos C, Skoumas J, Krinos X, Chloptsios Y, et al. Long-‐term fish consumption is associated with protection against arrhythmia in healthy persons in a Mediterranean region -‐ the ATTICA study. American Journal of Clinical Nutrition. 2007; 85(5):1385-‐1391.
135. Masson S, Marchioli R, Mozaffarian D, Bernasconi R, Milani V, Dragani L, et al. Plasma n-‐3 polyunsaturated fatty acids in chronic heart failure in the GISSI-‐Heart Failure Trial – Relation with fish intake, circulating biomarkers and mortality. American Heart Journal. 2013; 165(2):208-‐15. DOI:10.1016/j.ahj.2012.10.021.
136. Moertl D, Hammer A, Steiner S, Hutuleac R, Vonbank K, Berger R. Dose-‐dependent effects of omega-‐3-‐polyunsaturated fatty acids on systolic left ventricular function, endothelial function, and markers of inflammation in chronic heart failure of nonischemic origin: A double-‐blind, placebo-‐controlled, 3-‐arm study. American Heart Journal. 2011; 161(5):915.e1-‐915.e9. DOI:http://dx.doi.org/10.1016/j.ahj.2011.02.011.
137. Mozaffarian D. Fish, mercury, selenium and cardiovascular risk: C urrent evidence and unanswered questions. International Journal of Environmental Research and Public Health. 2008; 6(6):1894.
138. Erkkilä A, Schwab U, de Mello V, Lappalainen T, Mussalo H, Lehto S, et al. Effects of fatty and lean fish intake on blood pressure in subjects with coronary heart disease using multiple medications. European Journal of Nutrition. 2008; 47(6):319-‐28.
139. Erkkila A, Lichtenstein A, Mozaffarian D, Herrington D. Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenapausal women with coronary heart disease. American Journal for Clinical Nutrition. 2004; 80(3):626-‐632.
140. GISSI-‐HF investigators. Effect of n-‐3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-‐HF trial): A randomised, double-‐blind, placebo-‐controlled trial. The Lancet. 2008; 372:1223-‐30.
141. He K, Song Y, Daviglus M, Liu K, Van Horn L, Dyer A, et al. Accumulated evidence on fish consumption and coronary heart disease mortality: A meta analysis of cohort studies. Circulation. 2004; 109:2705-‐2711.
142. Hu F, Bronner L, Willett W, Stampfer M, Rexrode K, Albert C, et al. Fish and omega-‐3 fatty acid intake and risk of coronary heart disease in women. Journal of the American Medical Association. 2002; 287(14):1815-‐1821.
143. McKenney J, Sica D. Prescription omega-‐3 fatty acids for the treatment of hypertriglyceridemia. American Journal of Health-‐System Pharmacy. 2007; 64(6):595.
144. LJ. D, Perez-‐Martinez P, Lopez-‐Miranda J, Perez-‐Jimenez F. Long chain omega-‐3 fatty acids and cardiovascular disease: A systematic review. British Journal of Nutrition. 2012; 107(S2):S201-‐S213.
58
145. Musa-‐veloso K, Binns MA, Kocenas A, Chung C, Rice H, Oppedal-‐olsen H, et al. Impact of low v. moderate intakes of long-‐chain n-‐3 fatty acids on risk of coronary heart disease. British Journal of Nutrition 2011; 106(8):1129-‐1141.
146. Caslake M, Miles E, Kofler B, Lietz G, Curtis P, Armah C, et al. Effect of sex and genotype on cardiovascular biomarker response to fish oils: The FINGEN Study. American Journal of Clinical Nutrition. 2008; 88(3):618-‐29. DOI:88/3/618 [pii].
147. Micallef M, Garg M. Beyond blood lipids: phytosterols, statins and omega-‐3 polyunsaturated fatty acid therapy for hyperlipidemia. Journal of Nutritional Biochemistry. 2009; 20(12):927-‐939.
148. Meyer B, Swierk M, Russell K. Assessing long-‐chain n-‐3 polyunsaturated fatty acids: A tailored food-‐frequency questionnaire is better. Nutrition. 2012; 29(3):491-‐496
149. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): A randomised open-‐label, blinded endpoint analysis. The Lancet. 2007; 369(1090-‐1098)
150. Nilsson A, Radeborg K, Salo I, Björck I. Effects of supplementation with n-‐3 polyunsaturated fatty acids on cognitive performance and cardiometabolic risk markers in healthy 51 to 72 years old subjects: A randomized controlled cross-‐over study. Nutrition Journal. 2012; 11(1):99.
151. Rudkowska I, Paradis A, Thifault E, Julien P, Tchernof A, Couture P, et al. Transcriptomic and metabolomic signatures of an n-‐3 polyunsaturated fatty acids supplementation in a normolipidemic/normocholesterolemic Caucasian population. Journal of Nutritional Biochemistry. 2013; 24(1):54-‐61. DOI:http://dx.doi.org/10.1016/j.jnutbio.2012.01.016.
152. Bao D, Mori T, Burke V, Puddey I, Beilin L. Effects of dietary fish and weight reduction on ambulatory blood pressure in overweight hypertensives. Hypertension. 1998; 32:710-‐717.
153. Cabo J, Alonso R, Mata P. Omega-‐3 fatty acids and blood pressure. British Journal of Nutrition. 2012; 107(S2):S195-‐200.
154. Pase M, Grima N, Sarris J. Do long-‐chain n-‐3 fatty acids reduce arterial stiffness? A meta-‐analysis of randomised controlled trials. British Journal of Nutrition. 2011; 106(7):974-‐80.
155. Skulas Ray A, Kris-‐Etherton P, Harris W, West S. Effects of marine-‐derived omega-‐3 fatty acids on systemic hemodynamics at rest and during stress: a dose–response study. Annals of Behavioral Medicine. 2012; 44(3):301-‐308.
156. Xun P, Qin B, Nakamura Y, Kurth T, Yaemsiri S, Djousse L, et al. Fish consumption and risk of stroke and its subtypes: Accumulative evidence from a meta-‐analysis of prospective cohort studies. European Journal of Clinical Nutrition. 2012; 66(11):1199-‐207.
157. Phang M, Lincz L, Seldon M, Garg M. Acute supplementation with eicosapentaenoic acid reduces platelet microparticle activity in healthy subjects. Journal of Nutritional Biochemistry. 2012; 23(9):1128-‐1133. DOI:http://dx.doi.org/10.1016/j.jnutbio.2011.06.006.
158. Hassen L, Ueshima H, Curb J, Choo J, Lee S, Masaki K, et al. Significant inverse association of marine n-‐3 fatty acids with plasma fibrinogen levels in Japanese in Japan but not in whites or Japanese Americans. European Journal of Clinical Nutrition. 2012; 66(3):329-‐35.
159. Djousse L, Akinkuolie A, Wu J, Ding E, Gaziano M. Fish consumption, omega-‐3 fatty acids and risk of heart failure: A meta-‐analysis. Clinical Nutrition. 2012; 31(6):846.
160. He Z, Yang L, Tian J, Yang K, Wu J, Yao Y. Efficacy and safety of omega-‐3 fatty acids for the prevention of atrial fibrillation: A meta-‐analysis. Canadian Journal of Cardiology. 2013; 29(2):196-‐203. DOI:http://dx.doi.org/10.1016/j.cjca.2012.03.019.
161. Zampelas A, Panagiotakos D, Pitsavos C, Das U, Chrysohoou C, Skoumas Y, et al. Fish consumption among healthy adults is associated with decreased levels of inflammatory markers related to cardiovasular disease. Journal of the American College of Cardiology. 2005; 46:120-‐24.
162. Rangel Huerta O. Omega-‐3 long-‐chain polyunsaturated fatty acids supplementation on inflammatory biomakers: A systematic review of randomised clinical trials. British Journal of Nutrition. 2012; 107(S2):S159-‐S170..
163. Metroka C, Truong P, Gotto Jr A. Treatment of HIV-‐associated dyslipidemia: A role for omega-‐3 fatty acids. The AIDS Reader. 2007; 17(7):362-‐4, 367-‐73.
164. Mozaffarian D, Micha R, Wallace S. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: A systematic review and meta-‐analysis of randomized controlled trials. PLoS Medicine. 2010; 7(3)
165. Sala -‐ Vila A, Ros E, Sala-‐Vila A. Mounting evidence that increased consumption of [alpha]I[+ or -‐]-‐linolenic acid, the vegetable n-‐3 fatty acid, may benefit cardiovascular health. Clinical Lipidology. 2011; 6(4):365.
59
166. Gardener H, Wright C, Gu Y, Demmer R, Boden-‐Albala B, Elkind M, et al. Mediterranean-‐style diet and risk of ischemic stroke, myocardial infarction and vascular death: The Northern Manhattan Study. American Journal of Clinical Nutrition. 2011; 94(6):1458.
167. National Heart Foundation of Australia. Position statement. Fish, fish oils, n-‐3 polyunsaturated fatty acids and cardiovascular health. National Heart Foundation of Australia; 2008. http://testing.heartfoundation.org.au/SiteCollectionDocuments/Fish-‐position-‐statement.pdf.
168. Montonen J, Järvinen R, Reunanen A, Knekt P. Fish consumption and the incidence of cerebrovascular disease. British Journal of Nutrition. 2009; 102(5):750-‐756.
169. He K, Liu K, Daviglus ML, Mayer-‐Davis E, Jenny NS, Jiang R, et al. Intakes of long-‐chain n-‐3 polyunsaturated fatty acids and fish in relation to measurements of subclinical atherosclerosis. American Journal of Clinical Nutrition. 2008; 88:1111 -‐ 8.
170. Thies F, Garry J, Yaqoob P, Rerkasem K, Williams J, Shearman C, et al. Association of n-‐3 polyunsaturated fatty acids with stability of atherosclerotic plaques: A randomised controlled trial. The Lancet. 2003; 361 477-‐85.
171. Holub D, Holub B. Omega-‐3 fatty acids from fish oils and cardiovascular disease. Molecular Cell Biochemistry. 2004; 263:217-‐225.
172. Oh R, Beresford S, Lafferty W. The fish in secondary prevention of heart disease (FISH) survey -‐ Primary care physicians and ω-‐3 fatty acid prescribing behaviours. Journal American Board of Family Medicine. 2006; 19:459-‐67.
173. Grenon S, Conte M, Nosova E, Alley H, Chong K, Harris W, et al. Association between n-‐3 polyunsaturated fatty acids content of red blood cells and inflammatory biomarkers in patients with peripheral artery disease. Journal of Vascular Surgery. 2013; 58(5):1283-‐1290.
174. Silva P, da Silva G, de Souza A, Cardoso C, Fonseca C, Brito P, et al. Effects of omega-‐3 polyunsaturated fatty acid supplementation in patients with chronic chagasic cardiomyopathy: Study protocol for a randomised control trial. Trials. 2013; 14:379.
175. Aleksova A, Masson S, Maggioni A, Lucci D, fabbri G, Beretta L, et al. n-‐3 polyunsaturated fatty acids and atrial fibriliation in patients with chronic heart failure: The GISSI-‐HR trial. European Journal of Heart Failure. 2013; 15:1289-‐1295.
176. Miyoshi T, Ito H, Nihon R. Treatment of hypertriglyceridemia with omega-‐3 fatty acids. Japanese Journal of Clinical Medicine. 2013; 71(9):1650-‐1654.
177. Pirillo A, Catapano A. Omega-‐3 polyunsaturated fatty acids in the treatment of atherogenic dyslipidemia. Atherosclerosis Supplements. 2013; 14:237-‐242.
178. Braeckman R, Manku M, Bays H, Stirtan W, Soni P. Icosapent ethyl, a pure EPA omega-‐3 fatty acid: Effects on plasma and red blood cell fatty acid in patients with very high triglyceride levels. Prostaglandins, Leukotrienes and Fatty Acids. 2013; 89(4):195-‐201.
179. Macchia A, Romero M, D'Ettorre A, Tognoni G, Mariani J. Exploratory analysis on the use of statins with or without n-‐3 PUFA and major events in patients discharged for acute myocardial infarction: An observational retrospective study. PLoS ONE. 2013; 8(5):1-‐8.
180. Casula M, Sorana D, Catapano A, Corrao G. Long-‐term effect of high dose omega-‐3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-‐analysis of randomized, double blind, placebo controlled trials. Atherosclerosis Supplements. 2013; 14:243-‐251.
181. Nosaka K, Doi M, Mashima K, Iwamoto M, Kajiya M, Okawa K, et al. Early loading of omega-‐3 fatty acids decreases inflammation and in-‐hospital events in patients with acute myocardial infarction undergoing percutaneous coronary intervention. Journal of the American College of Cardiology. 2014; 63(12):A38.
182. Amiano P, Machon M, Dorronsoro M, Chairaque M, Barricarte A, Sanchez M, et al. Intake of total omega-‐3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and risk of coronary heart disease in the Spanish EPIC study cohort. Nutrition Metabolism & Cardiovascular Diseases. 2014; 24:321-‐327.
183. Grieger J, Miller M, Cobiac L. Investigation of the effects of a high fish diet on inflammatory cytokines blood pressure and lipids in older Australians. Food & Nutrition Research. 2014; 58:1-‐13.
184. Grieger J, McLeod C, Chan L, Miller M. Theoretical dietary modelling of Australian seafood species to meet long-‐chain omega 3 fatty acid dietary recommendations. Food & Nutrition Research. 2013; 57:1-‐10.
185. von Schacky C. Omega-‐3 index and cardiovascular health. Nutrients. 2014; 6:799-‐814.
60
186. Beckles-‐Willson N, Elliott T, Everard M. Omega-‐3 fatty acids (from fish oils) for cystic fibrosis: The Cochrane Database of Systematic Reviews; 2002
187. Oliver C, Jahnke N. Omega-‐3 fatty acids for cystic fibrosis. The Cochrane Library. 2011; (8) 188. Hu F, Cho E, Rexrode K, Albert C, Manson J. Fish and long-‐chain n-‐3 fatty acid intake and risk of
coronary heart disease and total mortality in diabetic women. Circulation. 2003; 107:1852-‐1857. 189. Gillen L, Tapsell L. Development of food groupings to guide dietary advice for people with
diabetes. Nutrition & Dietetics. 2006; 63:36-‐47. 190. Zhou Y, Changwei T, Jia C. Association of fish and n -‐3 fatty acid intake with the risk of Type 2
diabetes: A meta-‐analysis of prospective studies. British Journal of Nutrition. 2012; 108(03):408-‐417.
191. Biesalski H. Diabetes preventive components in the mediterranean diet. European Journal of Nutrition. 2004; 43:I26-‐I30.
192. Martinez-‐Gonzalez M, de la Fuente-‐Arrillaga C, Nunez-‐Cordoba J, Basterra-‐Gortari F, Beunza J, Vazquez Z, et al. Adherence to mediterranean diet and risk of developing diabetes: Prospective cohort study. British Medical Journal. 2008; 336:1348-‐1354.
193. Romaguera D. Mediterranean diet and Type 2 diabetes risk in the European prospective investigation into cancer and nutrition (EPIC) study: The InterAct project. Diabetes Care. 2011; 34(9):1913.
194. Lee C, Adler A, Forouhi N, Luben R, Welch A, Khaw K, et al. Cross-‐sectional association between fish consumption and albuminuria: The European Prospective Investigation of Cancer-‐Norfolk Study. American Journal of Kidney Disease. 2008; 52(5):876-‐86. DOI:S0272-‐6386(08)00579-‐9 [pii]10.1053/j.ajkd.2008.02.307.
195. Belalcazar L, Reboussin D, Haffner S, Reeves R, Schwenke D, Hoogeveen R, et al. Marine omega-‐3 fatty acid intake: Associations with cardiometabolic risk and response to weight loss intervention in the Look AHEAD (Action for Health in Diabetes) study. Diabetes Care. 2010; 33(1):197.
196. Hartweg J, Perera R, Montori V, Dinneen. SF, Ahawn N, Farmer A. Omega-‐3 polyunsaturated fatty acids (PUFA) for Type 2 diabetes mellitus. The Cochrane Library. 2009; 1
197. Friedberg C, Janssen M, Heine R, Grobbee D. Fish oil and glycemic control in diabetes. Diabetes Care. 1998; 21(4):494-‐500.
198. Giacco R, Cuomo V, Vessby B, Uusitupa M, Hermansen K, Meyer B, et al. Fish oil, insulin sensitivity, insulin secretion and glucose tolerance in healthy people: Is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-‐6 and n-‐3 fatty acids? Nutrition, Metabolism and Cardiovascular Disease. 2007; 17:572-‐580.
199. Patel P, Sharp S, Luben R, Khaw K, Bingham S, Wareham N, et al. Association between type of dietary fish and seafood intake and the risk of incident Type 2 diabetes: The European Prospective Investigation of Cancer (EPIC)-‐Norfolk cohort study. Diabetes Care. 2009; 32(10):1857-‐1863.
200. Brinton E, Ballantyne C, Bays H, Kastelein J, Braeckman R, Soni P. Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-‐2, residual elevated triglycerides (200-‐500 mg/dl), and on statin therapy at LDL-‐C goal: The ANCHOR study. Cardiovascular Diabetology. 2013; 12:100-‐110.
201. Zhang M, Picard-‐Deland E, Marette A. Fish and marine omega-‐3 polyunsaturated fatty acid composititon and incidence of Type 2 diabetes: A systematic review and meta-‐analysis. International Journal of Endocrinology. 2013; 2013:1-‐11.
202. Cormier H, Radkowska I, THifault E, Lemieux S, Couture P, Vohl M. Polymorphisms in fatty acid desaturase (FADS) gene cluster: Effects on glycemic controls following an omega-‐3 polyunsaturated fatty acid (PUFA) supplementation. Genes. 2013; 4:485-‐498.
203. Gopinath B, Buyken A, Flood V, Empson M, Rochtchina E, Mitchell P. Consumption of polyunsaturated fatty acids, fish, and nuts and risk of inflammatory disease mortality. American Journal of Clinical Nutrition. 2011; 93(5):1073-‐9.
204. Christensen J, Schmidt E, Svensson M. n-‐3 polyunsaturated fatty acids, lipids and lipoproteins in end-‐stage renal disease. Clinical Lipidology. 2011; 6(5):563.
205. An W, Lee S, Son Y, Kim S, Kim K, Han J, et al. Omega-‐3 fatty acid supplementation increases 1,25-‐dihydroxyvitamin D and fetuin-‐A levels in dialysis patients. Nutrition Research. 2012; 32(7):495-‐502.
61
206. MZ. R, Perunicic G, Pljesa S, Gluvic Z, Sobajic S, Djuric I, et al. Effects of N-‐3 PUFAs supplementation on insulin resistance and inflammatory biomarkers in hemodialysis patients. Renal Failure. 2007; 29(3):321-‐9.
207. Khosroshahi H, Toomatari S, Salamat S, Moin G, Khosroshani S. Effectiveness of omega-‐3 supplement on lipid profile and lipid peroxidation in kidney allograft recipients. Nephrology and Urology Monographs. 2013; 5(5):822-‐826.
208. Sabbatini M, Apicella L, Cataldi M, Maresca I, Nastasi A, Vitale S, et al. Effects of a diet rich in N-‐3 polyunsaturated fatty acids on systemic inflammation in renal transplant recipients. Journal of the American College of Nutrition. 2013; 32(6):375-‐383.
209. Shapiro H, Tehilla M, Attal-‐Singer J, Bruck R, Luzzatti R, Singer P. The therapeutic potential of long-‐chain omega-‐3 fatty acids in nonalcoholic fatty liver disease. Clinical Nutrition. 2011; 30(1):6-‐19. DOI:http://dx.doi.org/10.1016/j.clnu.2010.06.001.
210. Parker H, Johnson N, Burdon C, Cohn J, O'Connor H, George J. Omega-‐3 supplementation and non-‐alcoholic fatty liver disease: A systematic review and meta-‐analysis. Journal of Hepatology. 2012; 56(4):944-‐951.
211. Oya J, Nakagami T, Sasaki S, Jimba S, Murakami K, Kasahara T, et al. Intake of n-‐3 polyunsaturated fatty acids and non-‐alcoholic fatty liver disease: A cross-‐sectional study in Japanese men and women. European Journal of Clinical Nutrition. 2010; 64(10):1179.
212. Hunt W, McManus A. Women's health care: The potenial of long-‐chain omega-‐3 polyunsaturated fatty acids. Journal of Women's Health Care. 2014; 3(1):1-‐3.
213. Myers G, Davidson P. Maternal fish consumption benefits children's development. The Lancet. 2007; 369(9561):537-‐538.
214. Hibbeln J, Davis J, Steer C, Emmett P, Rogers I, Williams C, et al. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): An observational cohort study. The Lancet. 2007; 369(9561):578-‐85.
215. Mendez M, Torrent M, Julvez J, Ribas-‐fitó N, Kogevinas M, Sunyer J, et al. Maternal fish and other seafood intakes during pregnancy and child neurodevelopment at age 4 years. Public Health Nutrition. 2008; 12(10):1702-‐1710.
216. Makrides M, Collins CT, Gibson RA. Impact of fatty acid status on growth and neurobehavioural development in humans. Maternal and Child Nutrition. 2011; 7(S2):80-‐88.
217. Mozurkewich E, Berman D, Chilimigras J. Role of omega-‐3 fatty acids in maternal, fetal, infant and child wellbeing. Expert Review of Obstetrics & Gynecology. 2010; 5(1):125.
218. Klemens C, Salari K, Mozurkewich E. Assessing omega-‐3 fatty acid supplementation during pregnancy and lactation to optimize maternal mental health and childhood cognitive development. Clinical Lipidology. 2012; 7(1):93.
219. Xue F, Holzman C, Rahbar M, Trosko K, Fischer L. Maternal fish consumption, mercury levels and risk of preterm delivery. Environmental Health Perspectives. 2007; 115(1):42-‐47.
220. Guldner L, Monfort C, Rouget F, Garlantezec R, Cordier S. Maternal fish and shellfish intake and pregnancy outcomes: A prospective cohort study in Brittany, France. Environmental Health. 2007; 6(33) DOI:3310.1186/1476-‐069x-‐6-‐33.
221. Halldorsson T, Meltzer H, Thorsdottir I, Knudsen V, Olsen S. Is high consumption of fatty fish during pregnancy a risk factor for fetal growth retardation? A study of 44,824 Danish pregnant women. American Journal of Epidemiology. 2007; 166(6):687-‐696. DOI:10.1093/aje/kwm133.
222. Oken E, Radesky J, Wright R, Bellinger D, Amarasiriwardena C, Kleinman K, et al. Maternal fish intake during pregnancy, blood mercury levels, and child cognition at age 3 years in a US cohort. American Journal of Epidemiology. 2008; 167(10):1171-‐1181. DOI:10.1093/aje/kwn034.
223. Oken E, Østerdal M, Gillman M, Knudsen V, Halldorsson T, Marin S, et al. Associations of maternal fish intake during pregnancy and breastfeeding duration with attainment of developmental milestones in early childhood: A study from the Danish National Birth Cohort. American Journal of Clinical Nutrition. 2008; 88:789 –96.
224. Tinoco S, Sichieri R, Setta C, Moura A, Carmo M. n-‐3 polyunsaturated fatty acids in milk is associated to weight gain and growth in premature infants. Lipids in Health and Disease. 2009; 8(23):23.
225. Courville A, Harel O, Lammi-‐keefe C. Consumption of a DHA-‐containing functional food during pregnancy is associated with lower infant ponderal index and cord plasma insulin concentration. British Journal of Nutrition. 2011; 106(2):208-‐212.
62
226. Bakker E, Hornstra G, Blanco C, Vles J. Relationship between long-‐chain polyunsaturated fatty acids at birth and motor function at 7 years of age. European Journal of Clinical Nutrition. 2009; 63(4):499.
227. van de Elsen L, Noakes P, van der Maarel M, Kremmyda L, Vlachava M, Diaper N, et al. Salmon consumption by pregnant women reduces ex vivo umbilical cord endothelial cell activation. American Journal of Clinical Nutrition. 2011; 94(6):1418.
228. Jans A. PUFAs acutely affect triacylglycerol-‐derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity. American Journal of Clinical Nutrition. 2012; 95(4):825.
229. Rees A-‐M, Austin M-‐P, Owen C, Parker G. Omega-‐3 deficiency associated with perinatal depression: Case control study. Psychiatry Research. 2009; 166(2):254-‐259.
230. Rahmawaty S, Lyons-‐Wall P, Batterham M, Charlton K, Meyer B. Food patterns of Australian children ages 9 to 13 y in relation to ω-‐3 long chain polyunsaturated intake. Nutrition. 2014; 30:169-‐176.
231. dos Santos Vaz J, Kac G, Emmett P, Davis J, Golding J, Hibbeln J. Dietary patterns, n-‐3 fatty acids from seafood and high levels of anxiety symptoms during pregnancy: Findings from the Avon Longitudinal Study of parents and children. PLoS ONE. 2013; 8(7):1-‐9.
232. Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. Maternal supplementation with very-‐long-‐chain n-‐3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Pediatrics. 2003; 111:e39-‐e44.
233. Ström S, Helmfrid I, Glynn A, Berglund M. Nutritional and toxicological aspects of seafood consumption: An integrated exposure and risk assessment of methylmercury and polyunsaturated fatty acids. Environmental Research. 2011; 111(2):274-‐280.
234. Sinikovic D, Yeatman H, Cameron D, Meyer B. Women’s awareness of the importance of long-‐chain omega-‐3 polyunsaturated fatty acid consumption during pregnancy: Knowledge of risks, benefits and information accessibility. Public Health Nutrution. 2008; 12(4):562-‐569.
235. McNamara R, Nandagopal J, Strakowski S, Delbello M. Preventative strategies for early-‐onset bipolar disorder: Towards a clinical staging model. CNS Drugs. 2010; 24(12):983.
236. Cohen J, Bellinger D, Connor W, Shaywitz B. A quantitative analysis of prenatal intake of n-‐3 polyunsaturated fatty acids and cognitive development. American Journal of Preventive Medicine. 2005; 29(4):366-‐374.
237. Hughner R, Maher J, Childs N. Review of food policy and consumer issues of mercury in fish. Journal of the American College of Nutrition. 2008; 27(2):185-‐194.
238. Sanchez-‐Villegas A, Delago-‐Rodriguez M, Alonso A, Schlatter J, Lahortiga F, Majem L, et al. Association of the mediterranean dietary pattern with the incidence of depression. Archives of General Psychiatry. 2009; 66(10):1090-‐98.
239. Logan A. Omega-‐3 fatty acids and major depression: A primer for the mental health professional. BioMed Central Online. 2004; 3(25):1-‐8.
240. Crowe F, Skeaff C, Green T, Gray A. Serum phospholipid n-‐3 long-‐chain polyunsaturated fatty acids and physical and mental health in a population-‐based survey of New Zealand adolescents and adults. American Journal of Clinical Nutrition. 2007; 86(5):1278-‐85. DOI:86/5/1278 [pii].
241. Nurk E, Drevon C, Refsum H, Solvoll K, Vollset SE, Nygard O, et al. Cognitive performance among the elderly and dietary fish intake: The Hordaland Health Study. American Journal of Clinical Nutrition. 2007; 86(5):1470-‐8. DOI:86/5/1470 [pii].
242. Kalmijn S, Launer L, Ott A, Witteman J, Hofman A, Breteler M. Dietary fat intake and the risk of incident dementia in the Rotterdam study. Annals of Neurology. 1997; 42(5):776-‐782.
243. Kamphius M, Geerlings M, Tijhuis M, Kalmijn S, Grobbee D, Kromhout D. Depression and cardiovascular mortality: A role for n-‐3 fatty acids? American Journal of Clinical Nutrition. 2006; 84(6):1513-‐1517.
244. Parker G, Gibson N, Heruc G, Rees A, Hadzi-‐Pavlovic D. Omega-‐3 acids and mood disorders. American Journal of Psychiatry. 2006; 163(6):969-‐978, 1120.
245. Balanza -‐ Martinez V, Fries G, Colpo G, Silveira P, Portella A, Tabares -‐ Seisdedos R, et al. Therapeutic use of omega-‐3 fatty acids in bipolar disorder. Expert Review of Neurotherapeutics. 2011; 11(7):1029.
246. Gören J, Tewksbury A, Dufresne R, Weber S, Biglow M. The use of omega-‐3 fatty acids in mental illness. Journal of Pharmacy Practice. 2011; 24(5):452-‐471.
63
247. Appleton K, Woodside J, Yarnell J, Arveiler D, Haas B, Amouyel P, et al. Depressed mood and dietary fish intake: Direct relationship or indirect relationship as a result of diet and lifestyle? Journal of Affective Disorders. 2007; 104:217 -‐ 223.
248. Astorg P, Couthouis A, Bertrais S, Arnault N, Meneton P, Guesnet P, et al. Association of fish and long-‐chain n-‐3 polyunsaturated fatty acid intakes with the occurrence of depressive episodes in middle-‐aged French men and women. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2008; 78(3):171-‐182.
249. Nemets B, Stahl Z, Belmaker R. Addition of omega-‐3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. American Journal of Psychiatry. 2002; 159:477 -‐ 479.
250. Bogetto F, Bozzatello P, Bellino S. Efficacy of omega-‐3 fatty acids in the treatment of borderline personality disorder: A study of association with valporic acid. European Neuropharmacology. 2013; 23:399.
251. Amminger G, Chanen A, Ohmann S, Klier C, Mossaheb N, Bechdolf A, et al. Omega-‐3 fatty acid supplementation in adolescents with borderline personality disorder and ultra-‐high risk criteria for psychosis: A post hoc subgroup analysis of a double-‐blind, randomised controlled trial. Canadian Journal of Psychiatry. 2013; 58(7):402-‐408.
252. Giles G, Mahoney C, Kanarek R. Omega-‐3 fatty acids influence mood in healthy and depressed individuals. Nutrition Reviews. 2013; 71(11):727-‐741.
253. KHajehnasiri F, Bagher S, Allameh M, Ajkhondzadeh S. Effect of omega-‐3 and ascorbic acid on inflammation markers in depressed shift workers in Shaid Tondoyan oil refinery: A randomized double-‐blind placebo-‐controlled study. Journal of Clinical Biochemistry and Nutrition. 2013; 53(1):36-‐40.
254. Lim W, Gammack J, Van Niekerk J, Dangour A. Omega-‐3 fatty acid for the prevention of dementia 2006. Report No.: Art. No.:CD005379.pub2. DOI: 10.1002/14651858. CD005379.pub2.
255. Samieri C, Féart C, Letenneur L, Dartigues J, Pérès K, Auriacombe S, et al. Low plasma eicosapentaenoic acid and depressive symptomatology are independent predictors of dementia risk. American Journal of Clinical Nutrition. 2008; 88:714-‐21.
256. Connor W, Connor S. The importance of fish and docosahexaenoic acid in Alzheimer's Disease. American Journal of Clinical Nutrition. 2007; 85:929-‐930.
257. Morris M, Evans D, Bienias J, Tangney C, Bennett D, Wilson R, et al. Consumption of fish and n-‐3 fatty acids and risk of incident Alzheimer's Disease. Archives of Neurology. 2003; 60:940-‐946.
258. Morris M, Evans D, Tangney C, Bienias J, Wilson R. Fish consumption and cognitive decline with age in a large community study. Archives of Neurology. 2005; 62:1849-‐1853.
259. Grosso G, Galvano F, Marventano S, Malaguarnera M, Bucolo C, Drago F, et al. Omega-‐3 fatty acids and depression: Scientific evidence and biological mechanisms. Oxidative Medicine and Cellular Longevity. 2014; March 1-‐16.
260. Abete I, Goyenechea E, Zulet M, Martínez J. Obesity and metabolic syndrome: Potential benefit from specific nutritional components. Nutrition, Metabolism and Cardiovascular Diseases. 2011; 21:B1-‐B15.
261. Lopez-‐huertas E. The effect of EPA and DHA on metabolic syndrome patients: A systematic review of randomised controlled trials. British Journal of Nutrition. 2012; 107(S2):S185-‐S194.
262. Kastorini C, Milionis H, Esposito K, Giugliano D, Goudevenos J, Panagiotakos D. The effect of mediterranean diet on metabolic syndrome and its components: A meta-‐analysis of 50 studies and 534,906 individuals. Journal of the American College of Cardiology. 2011; 57(11):1299-‐1313.
263. Tousoulis D, Plastiras A, Siasos G, Oikonomou N, Miliou A, Thodoris. Omega-‐3 PUFAs improved endothelial function and arterial stiffness with a parallel anti-‐inflammatory effect in adults with metabolic syndrome. Atherosclerosis. 2014; 232:10-‐16.
264. Tabbaa M, Golubic M, Roizen M, Bernstein A. Docosahexaenoic acid, inflammation and bacterial dysbiosis in relation to peridontal disease, inflammatory bowel disease and the metabolic syndrome. Nutrients. 2013; 5:3299-‐3310.
265. He K, Liu K, Daviglus M, Jenny N, Mayer-‐Davis E, Jiang R, et al. Associations of dietary long-‐chain n-‐3 polyunsaturated fatty acids and fish with biomarkers of inflammation and endothelial activation. American Journal of Cardiology. 2009; 1(103 (9)):1238.1243.
266. Mangano K, Sahni S, Kerstetter J, Kenny A, Hannan M. Polyunsaturated fatty acids and their relationship with bone and muscle health in adults. Current Osteoporosis Reports. 2013; 11:203-‐212.
64
267. Hutchins-‐Wiese H, Kleppinger A, Annis K, Liva E, Lammi-‐Keefe C, Durham H, et al. The impact of supplemental N-‐3 long chain polyunsaturated fatty acids and dietary antioxidants on physical performance in postmenopausal women. The Journal of Nutrition, Health & Aging. 2013; 17(1):76.
268. Australian Institute of Health and Welfare. Overweight and obesity 2013 269. Tapsell L, Betterham M, Charlton K, Neale E, Probst Y, O'Sea J, et al. Foods nutritents or whole
diets: Effects of targeting fish and LCn3PUFA consumption in a 12mo weight loss trial. BMC Public Health. 2013; 13(1231):1-‐11.
270. Itariu B, Zeyda M, Hochbrugger E, Neuhofer A, Prager G, Schindler K, et al. Long-‐chain n-‐3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: A randomized controlled trial. American Journal of Clinical Nutrition. 2012; 96(5):1137.
271. Domingo J, Bocio A, Falcó G, Llobet J. Benefits and risks of fish consumption: Part I. A quantitative analysis of the intake of omega-‐3 fatty acids and chemical contaminants. Toxicology. 2007; 230(2-‐3):219-‐226.
272. Mahaffey K, Clickner R, Jeffries R. Methylmercury and omega-‐3 fatty acids: Co-‐occurrence of dietary sources with emphasis on fish and shellfish. Environmental Research. 2008; 107:20-‐29.
273. Gochfeld M, Burger J. Good fish/bad fish: A composite benefit-‐risk by dose curve. NeuroToxicology. 2005; 26:511-‐520.
274. Wennberg M, Stromberg U, Bergdahl I, Jansson J, Kauhanen J, Norberg M, et al. Myocardial infarction in relation to mercury and fatty acids from fish: A risk-‐benefit analysis based on pooled Finnish and Swedish data in men. American Journal of Clinical Nutrition. 2012; 96(4):706.
275. Ginsberg G, Toal B. Quantitative approach for incorporating methylmercury risks and omega-‐3 fatty acid benefits in developing species-‐specific fish consumption advice. Environmental Health Perspectives. 2009; 117(2):267-‐275.
276. Weaver K, Ivester P, Chilton J, Wilson M, Pandey P, Chilton F. The content of favorable and unfavorable polyunsaturated fatty acids found in commonly eaten fish. Journal of the American Dietetic Association. 2008; 108:1178-‐1185.
277. Raymond L, Ralston N. Selenium's importance in regulatory issues regarding mercury. Fuel Processing Technology. 2009; 90(11):1333-‐1338.
278. Arnold S, Lynn T, Verbrugge L, Middaugh J. Human biomonitoring to optimize fish consumption advice: Reducing uncertainty when evaluating benefits and risks. American Journal of Public Health. 2005; 95(3):393-‐397.
279. Roman H, Walsh T, Coull B, Dewailly É, Guallar E, Hattis D, et al. Evaluation of the cardiovascular effects of methylmercury exposures: Current evidence supports development of a dose–response function for regulatory benefits analysis. Environmental Health Perspectives. 2011; 119(5):607-‐614.
280. Sirot V, Leblanc J, Margaritis I. A risk-‐benefit analysis approach to seafood intake to determine optimal consumption. British Journal of Nutrition. 2012; 107(12):1812.
281. Garcia-‐Hernandez V, Gallar M, Sanchez-‐Soriano J, Micol V, Roche E, Garcia-‐Garcia E. Effect of omega-‐3 dietary supplements with different oxidation levels in the lipidic profile of women: A randomised controlled trial. International Journal of Food Science and Nutrition. 2013; 64(8):993-‐1000.