Transcript Power Point on Fish Oils

Essential Fatty Acids
Fish oils and Eicosanoids
Objectives
• Know what an Eicosanoid is
• Know the 2 essential fatty acids
• Understand the difference between Omega-3
and Omega-6
• Where do essential fatty acids come from
• Health benefits of Omega-3’s
• The benefits of fish oil supplements
• How Eicosanoids relate to essential fatty acids
and fish oil
• What EPA and DHA are and their health
benefits
• What are prostaglandins
• The role fish oil can play in inflammation
• The benefits of replacing essential fatty acids
with fish oil.
• Essential fatty acids, to include Omega-3 fatty
acids, are necessary for human health but the
body cannot manufacture them. Humans
must get these through food in our diet, for
many people reaching the recommended
amount of EPA and DHA through diet alone
may be difficult unless fish oil supplements
are integrated into the diet.
What are Eicosanoids?
• Eicosanoids are metabolites of arachidonic
acid derived from the action of the
cyclooxygenase (cyclooxygenase pathway) or
lypoxygenase enzymatic pathways.
• Eicosanoids are autocoids but not all
autocoids are eicosanoids
What do eicosanoids do?
• In biochemistry, eicosanoids (preferred IUPAC
name icosanoids) are signaling molecules
made by oxidation of 20-carbon fatty acids.
They exert complex control over many bodily
systems, mainly in inflammation or immunity,
and as messengers in the central nervous
system. The networks of controls that depend
upon eicosanoids are among the most
complex in the human body.
• Eicosanoids are derived from either omega-3
or omega-6 fatty acids.
• The ω-6 eicosanoids are generally proinflammatory; ω-3s are much less so.
• The amounts and balance of these fats in a
person's diet will affect the body's eicosanoidcontrolled functions, with effects on
cardiovascular disease, triglycerides, blood
pressure, and arthritis. Anti-inflammatory
drugs such as aspirin and other NSAIDs act by
downregulating eicosanoid synthesis.
• There are at multiple subfamilies of
eicosanoids, including the prostaglandins,
prostacyclins, the thromboxanes, lipoxins and
the leukotrienes. For each, there are two or
three separate series, derived either from an
ω-3 or ω-6 EFA. These series' different
activities largely explain the health effects of
ω-3 and ω-6 fats.
Omega 3 Fatty Acids
• Omega-3 fatty acids are considered an
essential fatty acid.
• We need them for our bodies to work
normally. Because essential fatty acids (ALA,
DHA, EPA) are not made in the body or are
inefficiently converted from ALA to EPA and
DHA, we need to get them from our diet .
Where do Omega 3 come from?
• There are two major types of omega-3 fatty
acids in our diets
– alpha-linolenic acid (ALA)
– eicosapentaenoic acid (EPA) to include
docosahexaenoic acid (DHA)
Natural sources of Omega 3
• EPA and DHA are produced by water plants such as
algae and are prevalent in marine animals.
• A shorter chain omega-3 fatty acid, α-linolenic acid
(ALA),6 is a prominent component of our diet as it is
found in many land plants that are commonly eaten,
but it does not provide the health benefits seen with
EPA and DHA.
• Although it is possible for the body to convert ALA to
EPA and DHA by enlongase and desaturase enzymes,
research suggests that only a small amount can be
synthesized in the body from this process
• EPA and DHA
– considered long-chain forms of omega-3
– found in fish, fish oil supplements, and algae
extract.
• ALA
– the short-chain form
– found in plant sources like walnuts, flax seed,
canola and soybean oil, and, to a lesser degree,
green leafy vegetables.
EPA
DHA
ALA
Benefits of Omega 3
• Omega-3 fatty acids are polyunsaturated fatty
acids that are essential nutrients for health.
• We need omega-3 fatty acids for numerous
normal body functions, such as controlling
blood clotting and building cell membranes in
the brain
• Omega-3 fatty acids are also associated with
many health benefits, including protection
against heart disease and possibly stroke
Benefits of DHA and EPA
• EPA and DHA are precursors to eicosanoids
and provide an anti-inflammatory effect
throughout the body
• These fatty acids are used in the formation
and fluidity of cell membranes, which help
with maintenance of blood pressure and heart
rate, nervous system function, and in
hemostatic regulation, consisting of blood
clotting and thromboxane production.
• Fish oil has been shown to have antiinflammatory effects, especially the
Eicosapentaenoic acids (EPA).
• They can improve overall function in joints as
well as limit the amount of other antiinflammatory drugs that a patient must
consume with conditions such as arthritis or
other inflammatory disorders such as
Inflammatory Bowel Disease.
Omega 6 fatty acids
• Linoleic acid, the shortest-chained omega−6
fatty acid, is an essential fatty acid.
• Arachidonic acid is a physiologically significant
omega−6 fatty acid and is the precursor for
prostaglandins and other physiologically active
molecules.
• Along with omega-3 fatty acids, omega-6 fatty
acids play a crucial role in brain function, as
well as normal growth and development.
• Also known as polyunsaturated fatty acids
(PUFAs), they help stimulate skin and hair
growth, maintain bone health, regulate
metabolism, and maintain the reproductive
system.
Dietary sources of Omega 6
• Four major food oils
– palm, soybeans, rapeseed, and sunflower
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poultry
eggs
avocado
nuts
– Cashews, pecans, pine nuts, walnuts
• hemp oil
• There are several different types of omega-6
fatty acids not all promote inflammation.
• Most omega-6 fatty acids in the diet come
from vegetable oils, such as linoleic acid (LA).
• Be careful not to confuse this with alphalinolenic acid (ALA), an omega-3 fatty acid.
Fine Balance
• A healthy diet contains a balance of omega-3
and omega-6 fatty acids.
• Omega-3 fatty acids help reduce
inflammation, and some omega-6 fatty acids
tend to promote inflammation.
• Some studies suggest that elevated intakes of
omega-6 fatty acids may play a role in
Complex Regional Pain Syndrome.
• The typical American diet tends to contain 14 25 times more omega-6 fatty acids than
omega-3 fatty acids.
Fish Oil Supplements
Fish Oil
• Fish Oil is extracted from the flesh of the fish.
It is primarily composed of two fatty acids
Docosahexaenoic Acid (DHA)
Eicosapentaenoic Acid (EPA)
And small portions of Alpa-Linolenic Acid (ALA).
• Fish do not actually produce omega-3 fatty
acids, but instead accumulate them by
consuming either microalgae or prey fish that
have accumulated omega-3 fatty acids,
together with a high quantity of antioxidants
such as iodide and selenium, from microalgae,
where these antioxidants are able to protect
the fragile polyunsaturated lipids from
peroxidation.
• EPA and DHA are precursors to eicosanoids
and provide an anti-inflammatory effect
throughout the body
• These fatty acids are used in the formation
and fluidity of cell membranes, which help
with the maintenance of blood pressure and
heart rate, nervous system function, and in
hemostatic regulation, consisting of blood
clotting and thromboxane production.
• EPA is a long chain fatty acid. It is the single
vital nutrient that controls communication
between nerve cells and the brain.
• DHA is another long chain fatty acid. It is
known as the building block of the brain cells
since it is the most important component that
makes up the brain
• EPA and DHA fatty acids are more commonly
found in cold water fish
– Fatty fish like salmon, mackerel, herring,
lake trout, sardines and albacore tuna are
high in omega-3 fatty acids.
• They provide about 1 gram of omega-3 fatty
acids in about 3.5 ounces of fish.
Common Uses for fish oil
• Fish oil helps with cholesterol by lowering levels
of LDL while also increasing levels of HDL
• This may limit the amount of prescription antihyperlipidemic drugs that a person might have to
take in their lifetime.
• Fish oil has been shown to influence cholesterol
by altering the production and catabolsim rates
of HDL apolipoproteins.
• The high rates of HDL can lead to a decrease in
atherosclerosis by eliminating excess cholesterol
from arterial cells.
Fish Oil, Drugs, and Inflammation
• Inflammation is a normal, protective response
to tissue injury caused by physical trauma,
noxious chemicals, or microbiologic agents.
• Inflammation is the body's effort to inactivate
or destroy invading organisms, remove
irritants, and set the stage for tissue repair.
• When healing is complete, the inflammatory
process usually subsides.
• However, inflammation is sometimes
inappropriately triggered by an innocuous
agent, such as pollen, or by an autoimmune
response, such as in asthma or rheumatoid
arthritis.
• In such cases, the defense reactions
themselves may cause progressive tissue
injury, and anti-inflammatory or
immunosuppressive drugs may be required to
modulate the inflammatory process.
Prostaglandins
• Prostaglandins: naturally occurring hormonelike substances that can accentuate
inflammation and thrombosis.
• All of the nonsteroidal anti-inflammatory
drugs (NSAIDs) act by inhibiting the synthesis
of prostaglandins.
• Role of prostaglandins as local mediators
• Prostaglandins and related compounds are
produced in minute quantities by virtually all
tissues.
• They generally act locally on the tissues in which
they are synthesized, and they are rapidly
metabolized to inactive products at their sites of
action.
• Therefore, the prostaglandins do not circulate in
the blood in significant concentrations.
Eicosanoids are produced
from fatty acids released
from membrane
phospholipids. In humans,
arachidonic acid is the major
precursor of the eicosanoids,
which include prostaglandins,
leukotrienes, and
Thromboxanes.
Actions of prostaglandins
• Many of the actions of prostaglandins are
mediated by their binding to a wide variety of
distinct cell membrane receptors that operate via G
proteins, which subsequently activate or inhibit
adenylyl cyclase or stimulate phospholipase C.3
• This causes an enhanced formation of
diacylglycerol and inositol 1,4,5-trisphosphate
(IP3). Prostaglandin F2a (PGF2a), the leukotrienes,
and thromboxane A2 (TXA2) mediate certain
actions by activating phosphatidylinositol
metabolism and causing an increase of intracellular
Ca2+.
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Functions in the body
Prostaglandins and their metabolites produced
endogenously in tissues act as local signals that finetune the response of a specific cell type. Their
functions vary widely depending on the tissue.
For example, the release of TXA2 from platelets
triggers the recruitment of new platelets for
aggregation (the first step in clot formation).
However, in other tissues, elevated levels of TXA2
convey a different signal; for example, in certain
smooth muscle, this compound induces contraction.
Prostaglandins are also among the chemical mediators
that are released in allergic and inflammatory
processes.
Prostaglandins,leukotrienes and
thromboxanes.
• All act on target cells close to their site of
formation and are rapidly degraded.
• Their roles include: inflammation, fever,
control of blood pressure,
clotting,reproductive processes & tissue
growth, sleep/wake cycle.
• Prostaglandin receptors:
• Prostaglandins & related compounds are
transported out of the cells that synthesize them.
• Most affect other cells by interacting with plasma
membrane G-protein coupled receptors.
• Depending on the cell type, the activated Gprotein may stimulate or inhibit formation of
cAMP, or may activate a phosphatidylinositol
signal pathway leading to intracellular Ca++
release.
• Although there is obvious therapeutic
potential in the ability to block specific
activities of prostaglandins, the physiologic
role of the receptors is only partially
characterized, and subtype-selective
antagonists remain elusive.
• A number of unrelated agents act as eicosanoid antagonists and inhibit
prostaglandin synthesis
• For example, cortisol inhibits phospholipase A activity, so that the
precursor of the prostaglandins, arachidonic acid, is not available.
• The NSAIDs,aspirin, indomethacin, and phenylbutazone all inhibit
prostaglandin endoperoxide synthase, and therefore prevent the synthesis
of the parent prostaglandins, PGG2 and PGH2.
• NOTE, however, that NSAIDS do not affect synthesis of the
leukotrienes.The lipoxygenases are not inhibited by NSAIDs.
• NOTE ALSO Aspirin is an irreversible inhibitor; the other nonsteroidal
antiinflammatory drugs are reversible within approximately 48 hours
Eicosanoid Antagonists
Corticosteroids
- Inhibit phospholipase A2 by anexins or lipocortins
- Inhibit PG, TX, and LT production block all pathways
NSAIDs
- Non selective COX-1 and COX-2 inhibitors
- Selective COX-2 inhibitors?
- Inhibit PG and TX production
- ASA is the only NSAID that irreversibly acetylates
(inactivate) COX
Zileuton, Zafirlukast
- Inhibit lipoxygenase or block LT receptor
- Inhibit the effect of LTs
Eicosanoid Antagonists
General consideration of the role of
the eicosanoids in clinical
pharmacology.
Therapeutic approach
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We seek to prevent the actions of autacoids by
Removal of the inflammatory trigger
Inhibiting cell activation
Inhibiting mediator synthesis
Receptor antagonists
• How do we decide which is the best approach
when faced with treating an inflammatory
problem?
Consider the nature of the condition!
• Bacterial infection/surgery?
Try antibiotics + NSAIDs
• Urticaria? Allergic rhinitis? Allergic conditions?
Try H1 receptor antagonists / antihistamines
• Inflammatory joint disease/elective surgery tooth pain,
fever and asthma?
Try Non-Steroidal (NSAID, i.e cyclo-oxygenase and L-O inhibitors) or
Steroidal (SAID) drugs
• Inflammation due to peptic ulcer
Try H2 receptor antagonists or the synthetic PGE2 misoprostol to
prevent ulcer in NSAID treated patients
Migraine Irritable Bowel syndrome
•
Antiserotonin (5-HT1D, 5-HT3/4)
• Note that Anti-PAF drugs are NOT yet available.
Six Products of Arachidonate Are of Clinical
Importance (generated by COX)
• 1- Alprostadil (PGE1): smooth muscle relaxing effect
• 2- Misoprostol (PGE1 derivative): prevents peptic ulcers
•
• 3- PGE2/ PGF2 : used in obstetrics
• 4- Latanoprost (PGF2 ) and topically active PGF2 : ophthalmology
• 5- Prostacyclin (PGI2): by endothelial cells; vasodilator; inhibits
platelet aggregation
• 6- Thromboxane (TXA2): aggregation and vasoconstriction (receptor
antagonists and synthesis inhibitors: used for cardiovascular
indications)
• An injury to the body
tissues releases
arachidonic acid, which is
converted to
prostaglandins that cause
pain, fever, and
inflammation.
• Analgesics reduce the
effects of prostaglandins
by inhibiting the enzyme
required for their
synthesis.
NSAIDS
• Because aspirin inhibits cyclooxygenase activity, it
diminishes the formation of prostaglandins and, thus,
modulates those aspects of inflammation in which
prostaglandins act as mediators. Aspirin inhibits
inflammation in arthritis, but it neither arrests the
progress of the disease nor induces remission
• The antipyretic and anti-inflammatory effects of the
salicylates are due primarily to the blockade of
prostaglandin synthesis at the thermoregulatory
centers in the hypothalamus and at peripheral target
sites.
Negative affects of using
pharmaceutical drugs (Aspirin) to treat
inflammation
• Gastrointestinal: The most common gastrointestinal (GI)
effects of the salicylates are epigastric distress, nausea,
and vomiting. Microscopic GI bleeding is almost universal
in patients treated with salicylates. [Note: Aspirin is an
acid. At stomach pH, aspirin is uncharged; consequently,
it readily crosses into mucosal cells, where it ionizes
(becomes negatively charged) and becomes trapped,
thus potentially causing direct damage to the cells.
Aspirin should be taken with food and large volumes of
fluids to diminish GI disturbances. Alternatively,
misoprostol may be taken concurrently.]
• Blood: The irreversible acetylation of platelet cyclooxygenase
reduces the level of platelet TXA2, resulting in inhibition of
platelet aggregation and a prolonged bleeding time. For this
reason, aspirin should not be taken for at least one week prior to
surgery. When salicylates are administered, anticoagulants may
have to be given in reduced dosage.
• Respiration: In toxic doses, salicylates cause respiratory
depression and a combination of uncompensated respiratory
and metabolic acidosis.
• Metabolic processes: Large doses of salicylates uncouple
oxidative phosphorylation. The energy normally used for the
production of ATP is dissipated as heat, which explains the
hyperthermia caused by salicylates when taken in toxic
quantities. There may be hyperglycemia and depletion of muscle
and hepatic glycogen.
• Hypersensitivity: Approximately fifteen percent of patients taking
aspirin experience hypersensitivity reactions. Symptoms of true
allergy include urticaria, bronchoconstriction, angioneurotic edema.
Fatal anaphylactic shock is rare.
• Reye syndrome: Aspirin given during viral infections has been
associated with an increased incidence of Reye syndrome, which is
an often fatal, fulminating hepatitis with cerebral edema. This is
especially encountered in children, who therefore should be given
acetaminophen instead of aspirin when such medication is required
to reduce fever.
• Drug interactions: Concomitant administration of salicylates with
many classes of drugs may produce undesirable side effects
Fatty Acids and Prostaglandins
• Fewer prostaglandins are made from omega 3 fatty acids as
compared to the omega 6 family of fatty acids that originate in the
diet from leafy vegetables and other plant sources.
• Omega 3 fatty acids compete with omega 6 fatty acids for the same
binding site on the COX 1 enzyme that converts the omega 6 fatty
acids to prostaglandin (which is why the COX 1 enzyme and its COX
2 cousin are the targets of anti-inflammatory drugs like ibuprofen).
The more omega 3 fatty acids present to block the binding sites, the
fewer omega 6 fatty acids are able to be converted to
prostaglandin.
• Although omega 3 fatty acids also are converted to prostaglandins,
the prostaglandins formed from omega 3 are generally 2 to 50
times less active than those formed from the omega 6 fatty acids
from dietary plants.
Positive Uses for Omega 3 Fatty Acids
• May assist in lowering high cholesterol
• Blocks inflammation channels
• Reduce symptoms of Rheumatoid arthritis
By insuring the body gets a sufficient amount of
DHA ad EPA from Omega 3 fatty acids derived
from fish oil people may need less mediations
and may have fewer health concerns in the
future.
Available Forms of Fish Oil
• Both EPA and DHA can be taken in the form of fish oil
capsules. Flaxseed, flaxseed oil, fish, and krill oils
should be kept refrigerated. Whole flaxseeds must be
ground within 24 hours of use, so the ingredients stay
active. Flaxseeds are also available in ground form in a
special mylar package so the components in the
flaxseeds stay active.
• Be sure to buy omega-3 fatty acid supplements made
by established companies who certify that their
products are free of heavy metals such as mercury,
lead, and cadmium.
How much to take?
• Dietary Reference Intakes (DRIs): Acceptable
Macronutrient Distribution Ranges from the
Food and Nutrition Board, Institute of
Medicine, National Academies recommends
Adults take n-3 polyunsaturated fatty acids a
(α-linolenic acid) 0.6–1.2 (g/day)
• Dosing for fish oil supplements should be based
on the amount of EPA and DHA, not on the total
amount of fish oil. Supplements vary in the
amounts and ratios of EPA and DHA. A common
amount of omega-3 fatty acids in fish oil capsules
is 0.18 grams (180 mg) of EPA and 0.12 grams
(120 mg) of DHA. Different types of fish contain
variable amounts of omega-3 fatty acids, and
different types of nuts or oil contain variable
amounts of ALA. Fish oils contain approximately 9
calories per gram of oil.
Side effects of fish oil supplements
• Medications for high blood pressure (Antihypertensive
drugs)
Using fish oil with drugs that lower blood pressure can
increase the effects of these drugs and may lower blood
pressure too much.
Some medications for high blood pressure include
captopril (Capoten), enalapril (Vasotec), losartan (Cozaar),
valsartan (Diovan), diltiazem (Cardizem), amlodipine
(Norvasc), hydrochlorothiazide (HydroDIURIL),
furosemide (Lasix), and many others.
• Birth control pills (Contraceptive drugs)
There is some evidence that birth control pills might
interfere with the triglyceride-lowering effects of
fish oil.
Some of these drugs include ethinyl estradiol and
levonorgestrel (Triphasil), ethinyl estradiol and
norethindrone (Ortho-Novum 1/35, Ortho-Novum
7/7/7), and others.
• Herbs and supplements that might slow blood clotting
High doses of fish oil seem to slow blood clotting. Taking
fish oil with other herbs that slow clotting might cause
bleeding in some people. These herbs include angelica,
clove, danshen, garlic, ginger, ginkgo, Panax ginseng, red
clover, turmeric, willow, and others.
• Vitamin E
Fish oil can reduce vitamin E levels. Researchers aren't
sure whether fish oil keeps vitamin E from being
absorbed from food or whether it causes the body to use
up vitamin E faster than it should.
Review
• Eicosanoids are derived from either omega-3 or omega-6
fatty acids.
• EPA and DHA are precursors to eicosanoids and provide an
anti-inflammatory effect throughout the body
• Fish Oil can improve overall function in joints as well as
limit the amount of other anti-inflammatory drugs that a
patient must consume with conditions such as arthritis or
other inflammatory disorders such as Inflammatory Bowel
Disease
• Fish Oil Versus NSAIDs have less negative reactions on the
body.
• We must supplement our body with DHA and EPA because
they are essential fatty acids our body does not make
• By supplementing with fish oil to obtain ones
fatty acid supply we can reduce and prevent
many medical conditions.
• Ongoing research continues to prove that
taking a fish oil supplement has many health
benefits.
– They range from lowering cholesterol and
reducing inflammation to preventing cancerous
cells from forming and macular degeneration.
Sources
• Source: Omega-6 fatty acids | University of Maryland Medical
Center
http://umm.edu/health/medical/altmed/supplement/omega6fatty-acids#ixzz2amhhcpLR
• Source: Omega-3 fatty acids | University of Maryland Medical
Center
http://umm.edu/health/medical/altmed/supplement/omega3fatty-acids#ixzz2amoksOVN
• The Nutrition source | Harvard School of Public Health
http://www.hsph.harvard.edu/nutritionsource/omega-3/
• http://www.nlm.nih.gov/medlineplus/druginfo/natural/993.html
• http://www.sciencedaily.com/releases/2006/04/060404085719.ht
m
• SOURCE: Dietary Reference Intakes for Energy, Carbohydrate, Fiber,
Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (2002/2005).
The report may be accessed via www.nap.edu.