Omega-3 Fatty Acids

Where is the most widely available dietary source of EPA and DHA found?

Cold water oily fish such as salmon, makerel, anchovies, sardines, herring and tuna (SMART)

Where is DHA the highest?

Retina and cerebral cortex

Incorporation of omgea-3s into mitochondrial membrane increases

oxidative stress which induces apoptosis

Fish contain how much mercury?

10-1,00 ppb

Typical western diets provide ratios of omega-6: omega-3 ranging from?

10:1 to 20:1

When over the counter fish oil supplements have been investigated, the frequency of excess oxidation is between what % of the products tested?

11-62%

Long chain omega-3 FA and cardiovascular disease

18% reduction in coronary events 9% reduction in cardiac deaths

EPA reduces major coronary events by what %

19

Healthy ratios of omega-6: omega-3 are?

1:1- 4:1

Heart tissue phospholipid DHA proportion vs. EPA

2% vs 0.5%

Effects of marine-derived n-3 polyunsaturated FAs on C-reactive protein, interleukin 6 and Tumor necrosis factor a

20% reduction in CRP 22% reduction in IL-6 11% reduction in TNF-a

4% of adults have blood mercury concentrations >

5.8 ug/L, the EPA's cut off dose without appreciable lifetime risk of harm

Greenland eskimos have an average intake of how many g EPA per day?

6

LA competes with ALA for access to?

6 desaturase

What decreases with age?

6 desaturase

What is the RLS in ALA conversion to EPA and DHA

6 desaturase

Dietary induced changes in the FAs composition of the plasma membrane is largely complete within how many weeks?

6 to 8

ALA to DHA in men is?

<.05

ALA to DHA in women of reproductive age is?

<0.1%

Inflammation occurs as?

increased blood flow and increased permeability across capillaries, which are driven by metabolites generated from the phospholipid membrane fatty acid arachidonic acid

Omega-3 FA and cardiovascular outcomes

w-3 FA may protect against vascular disease

Resolvins E1, Resolvins D1 and neuroprotectin D1 all inhibit neurtophil infiltration at the sites of inflammation by reducing?

E-selectin and ICAM-1 expression

Anti-proliferative action is greater for EPA and DHA?

EPA

Stronger activator of PPAR a

EPA

What are the precursors to the anti-inflammatory resolvins and neuroprotectin-D1

EPA and DHA

What down-regulates activation of NFkB

EPA and DHA

What is more effective in improving insulin sensitivity in rats

EPA and DHA

When LA concentrations are too high production of what can be limited?

EPA and DHA

5 Desaturase and 6 desaturase are also called?

Fatty acid desaturase 1 and fatty desaturase 2 (FADS1 and FADS2)

What is a neurotoxic and also can impair normal neurological development in a fetus or child?

Methylmercury

Why are EPA and DHA more susceptible to lipid oxidation than other FAs?

More double bonds (5-6)

Studies support that a wide range of chronic disease may be beneficially influenced by the increase intake of?

Omega-3s

A high ratio of what is positively correlated with depressed bone formation rates and bone mineral density?

Omega-6/ Omega-3

What has been reported in literature that could account for varying degrees of effectiveness and inconsistance in fish oil supplementation?

Oxidation product

PUFAs in serum cholesterol ester and oxidative DNA damage in men and women Conclusion:

Oxidative damage may be greater with higher concentration of long-chain n-2 PUFAs but lower with higher concentrations of n-6 PUFAs

Oxidative stress and redox are affected by?

Oxidative lipids

Most inflammatory prostaglandin, causes vasodilation and increased vascular permeability

PGE2

What directly activates the RANKL receptor of progenitor osteoclasts which result in their activation?

PGE2

What is a modulator of osteoblast activity and at moderate levels supports bone formation, but at high concentration promotes bone resorption

PGE2

With low omega-3 intakes cellular membranes become enriched with an excess or arachidonic acid which is a substrate for?

PGE2

What does EPA and DHA bind to and activates in order to inhibit activation of NFkB, hence limiting inflammatory actions

PPARy

EPA inhibits the release of arachidonic acid from phospholipids by competitively inhibiting?

Phospholipase A2

In addition to their role as major substrates for phospholipid membrane structure, cellular enerfy production and adipose storage, omega-3s are also involved in the modulation of?

Pleiotropic functional properties at the cellular level

The conversion of ALA to EPA and DHA occurs where?

Smooth Endoplasmic Reticulum Except for the final beta- oxidation step which occurs in a peroxisome

Compared to ALA, the consumption of what, results in a much higher EPA concentration, but not DHA

Stearidonic Acid

T or F n-3 PUFA reduces inflammation by selectively inhibiting monocyte activation

True

T or F omega-3 act pro-arrhythmic by favoring excess Ca2 release and triggering arrhythmias

True

T or F there is no evidence for greater bioavailability of Krill Oil vs Fish Oil

True

T or F, Increased seafood consumption outweighs the risk associated with mercury

True

T or F, Omega-3 mechanisms prevent excess ca2 from accumulating in the cardiac cells cytoplasm and may prevent development of arrhythmias?

True

T or F, n-3 PUFA can be supplemented to prevent the development and progression of atherosclerosis

True

T or F, provision of EPA and DHA reduces systolic blood pressure, while provision of >2grams reduces diastolic

True

T or F DHA is more cardioprotective than EPA

True DHA induces greater eNOS expression in vascular endothelial cells. Increasing vascular function and reducing BP

What happens during asthma

Vasocontriction Bronchospasm Increased vasular permeability

When are lipid carbon-centered radicals produced?

When free radicals, such as hydroxly radicals oxidize the p-p pie bond

Even though sharks, swordfish, tilefish and albacore tuna are high in omega3, why do they also have toxic substances?

Where they are at the top of food chain consuming toxins through biomagnification FDA recommend this limitation too

omega-3 FA and risk of major cardiovascular disease

omega-3 PUFA was not associated with lower risk

ALA to EPA biosynthesis is limited at?

0.2%

What throught the activation of PPARa will reduce skeletal muscle uptake of triacylglycerol synthesis pathways and increase free FA b-oxidation?

Adiponectine

The ratio of long-chain omega-6: omega-3 fatty acids directly affects?

The amount and type of eicosanoids that are produced

T or F fish oil reduces HR

True

One explanation for the poor conversion of ALA to DHA is that?

ALA is the most rapidly oxidized unsaturated FA and so a large portion of ingested ALA is B-Oxidized to acetyl- Coa

Role of NFkB

Activated by extracellular inflammatory stimuli, and then it translocates to the nucleus to activate the promoter regions of many other pro-inflammatory genes

EPA and DHA decrease triacyglycerol concentrations by regulating 2 nuclear transcription factors

Activation of PPAR-a increases hepatice b-oxidation via the activation of lipoprotein lipase leading to the reduction of the FA substrates for triacylglycerol synthesis Decreased activation of sterol regulatory element-binding protein-1c (SREBP-1) decreases lipogenesis via reduced production of FA synthase

What inhibits 6 and 5 desaturase and inhibits DHA and EPA?

Alcohol

Mechanisms of action for lowering rick of cardiovascular disease

Anti-thrombotic Anti-atherogenic Anti-arrhythmic Vasoprotective

Where will EPA and DHA compete and replace arachidonic acid?

At the sn-2 position of the glycerophospholipids

Potential routes of lipid oxidation include?

Auto-oxidation Photo-oxidation Metal-cataylzed oxidation

RBC membrane EPA and DHA composition positively correlate with?

Blood plasma, platelet, WBC, adipose, breast milk, skeletal and cardia muscle and brain gray matter

EPA reduces eicosanoid production by competitively inhibiting the enzyme?

COX and 5-LOX

What has much higher affinity for arachidonic acid?

COX and LOX

Why should farm-raised salmon be safe for men and women but avoided by children, pregnant and nursing women?

Concentration of these toxins are still below EPA cut-off Larger omega 3 to toxin ratio

After infancy, what cannot be synthesized from EPA to any appreciable extent?

DHA

Does DHA or EPA increase LDL in a direct comparison of the mean difference in increasing LDL from study to baseline to endpoint

DHA

Is DHA or EPA better for reducing triglycerides in a direct comparison of the mean difference in reducing triglycerides from study to baseline?

DHA

omega-3 and prostate cancer

DPA performed better than DHA, which performed better than EPA

What happens to arachidonic acid in the membrane of cells when you increase amount of dietary fish oil?

Decreases With the result being less substrate available for synthesis of eicosanoids from arachidonic

What is the only way to attain high levels of EPA and DHA in the blood/ or cell membrane?

Dietaty intake

At high enough concentration, what are suspected carcinogens?

Dioxin, PCB and Chlordane

Why are polyunsaturated FAs so susceptible to oxidation?

Double bonds between carbons in the polyunsaturated FAs are SP2 hybridized and the p-p pie bond electrons are easy to grab and pull away, especially by free radicals who are looking for an extra electron to achieve stability

Effect of EPA on response of cardiomyocytes to electrical pacing before perfusion with EPA and during EPA perfusion

EPA directly stabilize electrical activity

Fish oils contain Omega- 3 fatty acids...

Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA)

The higher capacity to up- regulate ALA conversion in women may be important for meeting the demands of the fetus and neonate for DNA. This may be due to the up- regulatory effects of?

Estrogen

Farm-raised salmon in what country has the higher PCB concentration?

Europe

T or F in large doses bleeding occurs?

F

T or F, there is evidence benefits and preference to take EPA over DHA?

F, no evidence

T or F, fish produce omega-3 FAs?

False They consume microalgea or prey fish that have omega3

Whose diet is rich in marine derived fish and showed lower prevalence of inflammation and lower incidence or related diseases?

Greenland Eskimos

What is the issue with farm-raised salmon?

Has lower mercury but high levels of dioxins, polychlorinated biphenyls (PCB) and chlordane

What is produced when fish oil oxidize and overtime break down into secondary oxidation products which cause unpleasant odors associated with rancid oils?

Hydroperoxides

Omega-3 FAs in fish oils are thought to be beneficial in treating?

Hypertriglyceridemia, heart disease, insulin resistance, cancer and neurodegenerative disease, ameliorating inflammatory disease, RA, osteoporosis, IBS and asthma

Three conditions for which fish oil and other omega-3 sources are most highly recommended

Hypertriglyceridemia, hypertension and preventing secondary cardiovascular disease

What can cause inflammation, atherosclerosis and DNA damage leading to carcinogenesis?

Lipid membrane peroxidation (lipid oxidation)

EPA concentration in all tissue is high or low?

Low

What plays a key role in regulation of gene expression in inflammatory responses by cells?

NFkB

Is there an association between omega-3 FA supplementation and risk of major cardiovascular disease?

No

Two transcription factors that play a role in inflammation

Nuclear factor k B (NFkB) and peroxisome proliferator activated receptor y (PPARy)

What can influence cellular ion channels altering the electrophysiology of excitable membranes and therefore directly influence cardiac rhythm and vascular tone and may prevent arrhythmias

Omega-3

What is a valid and reliable index of habitual dietary intake of omega-3 fatty acids

Red blood cell membrane EPA and DHA

EPA and DHA produce novel anti-inflammatory and inflammation resolving mediators called?

Resolvins

What inhibits IL-1 and TNF production

Resolvins E1, Resolvins D1 and neuroprotectin

DHA supplementation raises EPA levels through?

Retro- conversion

What cofounds efforts to establish cause and effect relationship between dietary EPA and DHA?

Retro-conversion

What is the role of Resolvin?

Shut off the ongoing inflammatory process thereby limiting tissue damage

n-3 PUFA supplementation on plasma soluble adhesion molecules

Significant decrease in plasma ICAM-1

Benefits of fish oil supplementation in hyperlipidemia

Significant decrease in triglycerides by 34% Significant increase in LDL by 6%

Omega-3 polyunsaturated FAs and the treatment of RA

Small but, no significance in reduction of swollen joints no significance in pain reduction no significance in reduction of CRP

PPAR-y is a transcription factor that serves as a tumor suppressor by activating the gene for?

Syndecan-1 (SDC-1), a proteoglycan which inhibits the phosphorylation and therefore activation of other transcription factors involved in cell divison

T or F omega-3 PUFA supplementation reduces plasma concentrations of sICAM-1

TRUE

T or F, EPA and DHA are found in all seafood and most fish oil capsule?

TRUE

T or F, n-3 FAs are positively associated with bone mineral accrual and thus will peak BMD in young men?

TRUE

How can you prevent fish burps?

Take with meals, get enteric-coated

Eicosanoids made from omega-3 FAs are often referred to anti-inflammatory but in reality...

They are just less inflammatory than those made from omega-6 fats by an order of 10 to 100 fold less potent

What happens if both omega-3 and omega-6 are present?

They will compete to be transformed into their respective eicosanoids

How are Resolvin E1 (RvE1), Resolvin D1 (RvD1) and neuroprotectin D1 (NPD1) produced?

Through COX-2 and 5-LOX enzymes

What is an essential fatty acid which plants synthesize

a- linolenic acid (ALA) Making Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) essential as well

what doe PUFAS do to triacyglycerol-derived skeletal muscle FA uptake and postprandial insulin sensitivity?

acutley effect increase

Omega-3 FA in white adipose tissue activate PPARy which transcriptionally activates the gene for?

adipokine adiponectine

Omega-3s may inhibit carcinogenesis through

anti-inflammatory (inhibition of NFkB) pro-apoptotic (inhibition of Bcl-2) anti-proliferative (inhibition of Ras, TGF-B1 ) anti-angiogenic (inhibition of VEGF) estrogen antagonism (downregulation of estrogen synthesis of antagonism of estrogen receptors such as EGFR)

Reasons why some articles show benefits in Omega-3 and others dont

dose of EPA and DHA below anti-inflammatory threshold lipid peroxidation of the fish oil supplement genetic variants of FADS1 and FADS2 genes

Who does omega-3 prevent calcium overload?

inhibiting the activity of L-type Ca2 channels during periods of stress and increase the activity of cardiac ca2/Mg2 ATPase active transports responsible for moving calcium back into the SR from cytosol

MI relationship with mercury and FAs from fish

risk-benefit MI risk may be reduced by consumption of fish high in PUFA and low in methylmercury

How is it that fish oil supplements do not contain high amounts of mercury?

smaller fish mercury binds to protein, not oil Mercury may be reduced or removed during processing

On September 8, 2004, the FDA gave "qualified health claim" status to EPA and DHA omega-3 FAs stating?

supporting that consumption of EPA and DHA omega-3 FAs may reduce risk of coronary heart disease