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Learning Center - Omega-3 Liquid Supplement

Omega 3 Liquid - High Concentration, Best absorption

Lemon Flavor

More than 600 scientific studies from around the world continue to prove the success of Omega-3 Liquid Supplement.

DHA & EPA supplementation shows great promise in the following conditions:

Arthritis, Cardiovascular disease, Cancer, Attention deficit disorder, Autism, Improve vision , Irritable bowel and Chron disease, Increasing energy levels (Fibromyalgia), Weight loss, Auto immune disorders, PMS and Menopause (hormonal changes), Skin, hair and nail health, Improving cognitive function, strengthening sexual function, Reducing inflammation, Stress, Anxiety, Insomnia and Brain function. Hyperactive children, Epilepsy, Pregnancy (in the development of child's brain)

 

Liquid - Omega 3 High concentration compared to Omega 3 - Capsules :

1. Every Capsule (pill) is covered by gelatin (made of plants or animals).

The gelatin has to be dissolved in order for the oil to get to the intestine and be absorbed.

2. For the gelatin to be dissolved, we need specific stomach enzymes.

Only after it is dissolved the oil will escape the pill and pass to the intestine to be absorbed there.

Some people do not have these enzymes at all, or have not enough of them, so we can't know if the oil is completely absorbed in the intestine.

3. Each capsule contains ~ 500 mg. Omega 3 (pure).

The Suggested dose per day for Omega 3 is: 1.5 - 3 grams.

In order to achieve the recommended dose, one should take several pills a day.

The pills are large in size, and for some people hard to swallow. Taking a big quantity of pills every day is not enjoyable.

 

Therefore:

Liquid Omega 3 is the best choise for you.

-The liquid is high in concentration.

-One teaspoon equals 1.5 grams of pure Omega 3.

-All of the oil is completely absorbed in the intestine.

-There is no need to dissolve the gelatin.

-No fish smell or taste.

-Comes in lemon flavor.

-Tolerable and easy to be taken by infants, children, adults, seniors and others.

 

Eye conditions and Fish Oils

The fish oils eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) appear to have myriad effects on the eye. Docosahexaenoic acid, when combined with vitamin A, has been claimed to slow progression of retinitis pigmentosa (RP) in certain patients: For example, in patients beginning treatment with 15,000 IU/day vitamin A (retinyl palmitate), adding 1,200 mg/day DHA slows progression of RP for 2 years. A diet high in omega-3 fatty acids and fish and low in linoleic acid is associated with a relatively decreased risk of advanced AMD.


Symposium Highlights -- Omega-3 Fatty Acids: Recommendations for Therapeutics and Prevention  CME

Heather Hutchins, MS, RD

Introduction

Fish oil supplementation has waxed and waned in popularity over the past decade. In the late 1990s when large clinical trials such as the GISSI study were published supporting the cardiovascular benefits of omega-3 fatty acids, fish oil became one of the most sought after supplements. However, due to fish oil's less than desirable taste characteristics, it was not well tolerated by even its most ardent supporters. Improved molecular distillation processing has helped to enhance fish oil's purity and flavor and there are now even more studies to support the benefits of fish oil supplementation that reach beyond heart health. A recent symposium at Columbia University featured leaders in the field of omega (n)-3 fatty acid research. This article highlights information presented at the Omega-3 Fatty Acids: Recommendations for Therapeutics and Prevention Symposium, Institute of Human Nutrition, Columbia University College of Physicians and Surgeons, New York.

The goals of the symposium were to describe the functions of n-3 fatty acids (namely the long chain [LC] eicosapentaenoic acid (EPA) C20:5n-3, and docosahexaenoic acid (DHA) C22:6n-3), raise awareness of the adverse impacts of inadequate n-3 fatty acid intake, and translate research findings related to LC n-3 fatty acids into strategies for improved health. This symposium also provided an evidence-based foundation for possible Food and Drug Administration (FDA) recommendations regarding n-3 fatty acids, and argued that n-3 fatty acids are "important from womb to tomb."

Background

Omega-3 fatty acids and their counterparts, n-6 fatty acids, are essential polyunsaturated fatty acids (PUFA) because they cannot be synthesized de novo in the body. The major sources of 18-carbon n-3 essential fatty acids (linolenic acid [LNA]), are flax seed, soybean, canola, wheat germ, and walnuts oils. Linoleic acid (LA), the 18 carbon n-6 essential fatty acid, is found in safflower, corn, soybean, and cottonseed oils; meat products are a source of the LC n-6 fatty acid, arachidonic acid (AA) (C20:4n-6). The 20-and 22-carbon PUFA sources are fish and fish oils.

The 18-carbon PUFAs derived from plant sources can be converted (although not efficiently) to their longer chain and more metabolically active forms AA, EPA, and DHA. The conversion of n-3 and n-6 fatty acids uses the same enzyme pools (as shown in Figure 1). Through a series of desaturations and elongations, LA is converted to AA, while LNA is converted to EPA and further elongated to DHA. The shorter chain n-3 fatty acid food sources such as canola oil, flax seed, and leaf plants reportedly have little effect on tissue DHA and EPA concentrations.

AA and EPA, both 20-carbon fatty acids, are precursors to various eicosanoids. Most research has focused on prostaglandins, thromboxanes, and leukotrienes derived from AA and EPA. AA is a prominent precursor to highly active eicosanoids, while EPA is a precursor to less metabolically active eicosanoids. AA and EPA reside in the membrane phospholipid bilayer of cells. AA is a precursor to series 2 prostaglandins and thromboxanes and series 4 leukotrienes. The series 2 and 4 eicosanoids metabolized from AA can promote inflammation, and also can act as vasoconstrictors, stimulate platelet aggregation and are potent chemotoxic agents dependent on where in the body the eicosanoids are activated. EPA is a precursor to series 3 prostaglandins and thromboxanes and series 5 leukotrienes; they are less potent than the series 2 and 4 counterparts and act as vasodilators and anti-aggregators.

Phospholipase A 2 is stimulated by physiologic agonists that cleave the fatty acid from the phospholipid bilayer. The fatty acids are then converted to eicosanoids via the cyclooxygenase (COX) or lipoxygenase (LOX) pathways (Figure 2). N-6 and n-3 fatty acids compete for the COX or LOX enzymes to form eicosanoids. Therefore, adequate EPA in phospholipid pools allows for a decrease in the amount of eicosanoids produced from AA possibly by reducing the amount of enzyme available for conversion of AA to prostaglandins and leukotrienes; in this respect, EPA is considered anti-inflammatory.

DHA is a 22-carbon fatty acid and therefore not directly converted to eicosanoids; however, DHA can be retro-converted to EPA. DHA is a prominent fatty acid in cell membranes, it is present in all tissues and is especially abundant in neural (60% of the human brain is comprised of PUFAs, predominately DHA) and retinal tissue and essential in visual and neurologic development.

To date, research studies of n-3 fatty acids have produced conflicting results, largely because of inconsistencies in study design (observational vs. interventional). Variances in sample population, as well as varied amounts and duration of n-3 fatty acid supplementation also contribute to the complexity of results. Lecturers at the Omega-3 Fatty Acid Symposium sought to summarize the current literature, to ascertain biologic roles of specific omega-3 fatty acids, and tease out dietary recommendations based on the best evidence available.

Heather Hutchins, MS, RD , Registered Dietitian, Zone Labs, Inc., Marblehead, Massachusetts

Charles P Vega, MD , Associate Professor, Residency Director, Department of Family Medicine, University of California, Irvine

Disclosure: Heather Hutchins, MS, RD, has disclosed that she is employed by Zone Labs, Inc.

Disclosure: Charles Vega, MD, FAAFP, has disclosed that he has received grants for educational activities from Pfizer.

 

Omega-3 Fatty Acids and Pregnancy

Craig L. Jensen, MD

There has been a wide range of studies related to n-3 fatty acids and pregnancy. Outcome measures include gestational length and birth weight, preeclampsia, recurrent miscarriages, and maternal depression. Observational studies have found positive associations between fish intake and gestational length and birth weight. In a randomized multicenter trial, supplementation of 2.7g EPA and DHA from 20 weeks gestation or 6.1 g EPA and DHA from 33 weeks gestation reduced risk of preterm delivery, while others found no effect on gestational length. A study by Smuts and colleagues found that 1 DHA egg supplementation (~133 g DHA per egg) during the last trimester increased duration of gestation by 6 days in a predominately African American sample compared to that in controls.

Preeclampsia is a common problem during pregnancy, especially as maternal age increases. Observational data of potential effects of n-3 fatty acids on preeclampsia and related conditions show benefit; however, randomized, controlled studies have not found definitive effects of fish oil on preeclampsia.

The potential effects of n-3 fatty acids and recurrent miscarriages are promising. A pilot study supplemented fish oil in patients with persistent anti-phospholipid syndrome associated recurrent miscarriages and found over a 3-year period, 86% of the patients had well babies.

Maternal DHA levels decline during pregnancy (as well as postpartum) as DHA is transferred to the fetus or newborn to aid in neural development. Clinical depression has been associated with low levels of n-3 fatty acids, particularly DHA. A large, multi-country observational study of postpartum depression found a negative correlation between seafood consumption and/or breast milk DHA concentrations and postpartum depression;however, AA and EPA had no relationship with postpartum depression. Small intervention studies have yet to support this association.

Although the literature is limited in the area of n-3 fatty acids and pregnancy-related outcomes, expert panels recommend 300 mg/day of DHA for pregnant or lactating females.

Omega-3 Fatty Acids and Cognitive and Visual Development in Infancy

Susan E. Carlson, MD

There is definitive evidence that DHA is essential in cognitive and visual development because DHA is concentrated in the brain and retina.

Supplementation of approximately 0.3% DHA and approximately 0.43% to 0.72% AA of total lipids in formulas may lead to improved visual acuity compared to formulas supplemented with

LA and LNA. Supplementation of similar amounts of DHA and AA and follow-up testing at 18 to 24 months found no differences between formula groups. The discrepancies of these study results may be attributed to testing global abilities such as visual acuity rather than specific areas of cognitive development such as visual recognition memory.

Studies may also be limited by use of age-inappropriate developmental test design, sample size, DHA dosage, inconsistencies in the control diets, or intrauterine exposure to DHA. To best advance work in this field, longitudinal, collaborative efforts between dietitians, pediatricians, and developmental neuroscientists are needed. The specific benefits of adequate DHA intake during periods of rapid brain development may not be measurable until older ages. Carlson discussed the positive long-term effects of early DHA supplementation related to higher Bayley Psychomotor Developmental Index (PDI) (gold standard for neurological development, measures body control, coordination and fine motor skills) in scores at 30 months, higher IQ at 4 years, higher MFFT (Matching Familiar Figures Test) score and speed at 6 years, and lower diastolic and mean blood pressure at 6 years of age.

Infant development studies often compare formula to human milk. Human milk levels vary and the United States is considered an "at risk population" for low DHA levels, because US women consume lower levels of DHA compared to intake in other countries. Human milk DHA content varies primarily as a result of mother's dietary intake differences. The highest levels of DHA in human milk are found in the Japanese and marine China female populations. The United States has some of the lowest levels of DHA in human milk. In the United States, DHA was added to infant formula in 2002. To reach worldwide median human milk DHA consumption levels, formula should contain 0.3% to 0.4 % DHA and women who are breastfeeding should consider supplementation -- current recommendations are 300 mg/day. Arachidonic acid should also be added to formulas to mimic that of human milk at a median range of 0.4% to 0.6% AA of total fatty acids in the formula.

Human Distribution of Docosahexaenoic Acid and Eicosapentaenoic Acid

Linda M. Arterburn, PhD

The process to convert LNA to EPA and DHA does not yield significant amounts of either LC n-3 PUFA. In males, 3% to 8% of 1.3 g LNA is converted to EPA and 0% to 4% of the EPA is converted to DHA. In females, 21% of EPA is converted and 9% is then elongated to DHA. The conversion is reduced even further by diets high in n-6 fatty acids because of the competition between the n-6 and n-3 pathways. EPA supplementation results in increased EPA and decreased AA levels in the plasma phospholipids, but no increase in DHA.

DHA supplementation leads to a rapid increase in plasma DHA concentrations and a time- and dose-dependent decrease in AA and a small increase in EPA. Dose dependent saturation of the plasma phospholipids occurs within 4 weeks with supplementation of 2 g DHA/day with a washout period of greater than 24 weeks. EPA supplementation takes approximately 2 weeks to reach the same state as DHA in the whole plasma, while the washout period is much shorter: about 4 weeks. EPA saturation levels have yet to be determined. Distribution of PUFA differs in the plasma. Greater amounts of DHA are found in the plasma phospholipids; however, EPA is more evenly distributed. This is reflected in DHA and EPA human milk levels. Milk DHA increases rapidly with supplementation, while milk EPA remains lower and more constant.

Human tissue is responsive to DHA and EPA supplementation at differing levels as well. The rectal epithelium is particularly selective of DHA, whereas muscle tissue is selective of EPA. There is also a strong correlation between plasma and red blood cell DHA and EPA amounts. Plasma DHA concentrations increase rapidly in response to oral fatty acid intake and remain in a steady state with continued consumption of DHA. Red blood cells are slower to turn over and therefore, do not show a rapid increase with increased fatty acid intake. Long-term there is a strong correlation between plasma and red blood cell DHA and EPA contents. Arterburn concluded that DHA is important to supplement, with or without EPA. LNA supplementation does not reach the same levels as DHA supplementation. To saturate the plasma, 2 g DHA per day is needed for 1 month; to saturate the tissues, 3 to 6 months; and less than 1 week for DHA supplementation to increase human milk concentrations. To remain at saturation levels in the plasma, tissues, or human milk, continued supplementation is necessary.

Omega-3 Fatty Acids and Cardiovascular Disease

Jan Breslow, MD

There are a number of studies to support fish intake as a preventive measure in cardiovascular disease (CVD). In a prospective study of healthy males, low baseline total n-3 fatty acid, EPA, and DHA blood levels are associated with a greater risk of sudden death. The DART (Diet and Reinfarction Trial) study encouraged male myocardial infarction survivors to consume more oily fish (approximately 500 to 800 mg/day of n-3 fatty acids) and found a 29% reduction in total mortality. A subgroup from this study chose to take fish oil capsules providing 450 mg EPA and DHA per day; this group had a 62% reduction in CVD-related death and a 56% reduction in all-cause mortality. The GISSI prevention trial, an Italian study of post-myocardial infarction patients, showed that after 3.5 years, those receiving n-3 fatty acids (850 mg/day) had a 20% reduction in overall mortality, 30% reduction in coronary mortality, and 45% reduction in sudden death.

The proposed mechanisms by which n-3 fatty acids might influence CVD are via anti-arrhythmic properties, decreasing blood pressure, lowering triglyceride levels, stimulating endothelial-derived nitric oxide, decreasing platelet aggregation, and/or decreasing pro-inflammatory eicosanoids. There is evidence to suggest that the n-3 fatty acids prevent arrhythmias by stabilizing the myocardium.

A recent multicenter randomized placebo-controlled trial reported more ventricular tachycardia (VT) and ventricular fibrillations (VF) in patients with implantable cardioverter defibrillators (ICD) who were randomized to receive 1.3 g EPA and DHA per day compared to controls who received olive oil. The fish oil group reported more VT and VF events; however, the fish oil group had lower total mortality (although not significant, P = .16) and fewer hospitalizations for a neurologic conditions ( P = .04). If the mechanism for fish oil's benefits in decreasing sudden death is anti-arrhythmic, it may not be due to decreased risk of VT and VF.

Breslow's research suggests that DHA (supplemented at a level of 2 g/d) favorably alters CVD risk factors in overweight and obese individuals. Future research should review the role of n-3 fatty acids in secondary prevention as well as in the immediate, post-MI period because the greatest reduction of cardiac mortality is achieved in the first 9 months. Research must control for the type of n-3 fatty acid studied (vegetable vs marine source), EPA vs. DHA, and compare n-6 to n-3 fatty acids. Future investigations are required to further evaluate the anti-arrhythmic effects of n-3 fatty acids, as well as their systemic anti-inflammatory properties and immune modulatory effects.

Omega-3 Fatty Acids and Mental Health

Joseph Hibbeln, MD

LC n-3 fatty acids have been shown to reduce risk and/or treat psychiatric disorders including depression, schizophrenia, and aggression/hostility; however, the evidence to date is not robust and recommendations must be given with caution. There are no data to support a clear dose response to n-3 fatty acids, but EPA and DHA appear to work better together than alone. Hibbeln stressed the importance of measuring tissue levels of DHA and EPA in future research with the statement "the tissue is the issue." Dietary supplementation of 1 g/day of EPA appears to be effective in reducing psychotic, depressive and aggressive symptoms.

The RDA for n-3 fatty acids for mental health might best be estimated by reviewing cross-nation data and US data at the point in which the relative risk of developing a psychiatric illness is lowest. Epidemiologic data support that nations with the highest seafood intakes (and highest n-3 fatty acid intakes) have the lowest levels of major depression, bipolar disorder, and homicide. Japan has the lowest levels of depression (0.12% of population), Iceland the lowest levels of bipolar depression, and Hong Kong with the lowest homicide levels. These countries also have the highest seafood consumption (pounds/person/year) estimating 730 mg/day, 1000 mg/day and 730 mg/day EPA/DHA, respectively. Conversely, the United States reports major depression affecting approximately 3% of the population and our estimated daily intake of EPA and DHA is 180 mg/day. From these data, Hibbeln speculated that 180 or 500 mg/day of supplemental n-3 fatty acids are inadequate, 750 mg/day is possibly adequate, and 1000 mg/day of LC n-3 fatty acids is clearly adequate for lowering risk of psychiatric disorders.

Hibbeln also discussed the importance of balancing the n-6/n-3 ratio because both fatty acid groups compete for elongation and desaturation. Dietary intake of LA and LNA interact to determine pools of n-3 eicosanoid precursors in the tissue. Keeping dietary n-3 fatty acid intake constant, LC n-3 fatty acids in tissues can be increased by lowering the intake of LA.

Omega-3 Fatty Acids and Dementia

Ernst Schaefer, MD

Epidemiologic data indicate that in addition to age, there are at least 3 significant risk factors for dementia and Alzheimer's disease: apoE4 genotype, elevated plasma homocystine levels, and decreased plasma DHA. ApoE4 interacts with brain proteins to predispose people to dementia. Data from the Longitudinal Framingham Study suggest that ApoE4 carriers had approximately a 2.5-fold increased risk of dementia. Homocystine appears to be a direct vascular toxin. Those with increased homocystine levels in plasma were found to have a 1.9-fold increase in dementia. Approximately 40% of fatty acid phospholipids in the brain are DHA. Individuals with dementia have lower plasma phospholipid DHA levels in the brain compared to controls. Prospective studies have reported consumption of at least 1 fish serving per week decreases risk of Alzheimer's disease by 60%. Preliminary data suggest that after adjustment for age, gender, apoE genotype, and homocystine levels, the top quartile of plasma DHA of approximately 2.7 or more servings of fish/week or 180 mg or more DHA/day is associated with 50% decreased risk of dementia.

Schaefer concluded that 3 or more fish servings per week or at least 1 fish oil capsule per day (greater than 180 mg DHA/day) to raise DHA levels and supplementing or consuming adequate amounts of vitamins B6, B12, and folate (to decrease homocystine levels) could decrease the incidence of dementia.

Omega-3 Fatty Acids and the Metabolic Syndrome

Yvon Carpentier, MD

"The Metabolic Syndrome" is a diagnosis given to individuals who have 3 or more of the following risk factors: abdominal obesity (waist circumference > 102 cm for males, > 88 cm for females), serum triglycerides (TG) > 150 mg/dL, high density lipoprotein (HDL) cholesterol < 40 mg/dL, blood pressure > 130/85 mm Hg, and fasting plasma glucose > 110 mg/dL. The prevalence of metabolic syndrome is approximately 44% of the US population 50 years of age or older.

The metabolic syndrome is associated with gene variations, insulin resistance, and dyslipidemia. In human studies, 3 weeks of fish oil supplementation (1.1 g EPA and .7 g DHA/day) in healthy volunteers decreased insulin response to oral glucose load by approximately 40% with lower glucose oxidation and higher fat oxidation. Glycogen storage was increased and an unchanged glycemic response suggested improved insulin sensitivity.

Omega-3 fatty acids are considered a valuable nutritional tool to prevent insulin resistance associated with obesity; however, they do not appear to be efficient in reversing established type 2 diabetes.

In controlled trials, n-3 supplementation has also been found to decrease TG levels and thus the TG/HDL ratio. Supplementation of 4 g EPA/DHA per day for 6 weeks resulted in a 20% TG decline in mildly hyperlipidemic middle-aged men. Reductions of the TG/HDL ratio have also been found in postmenopausal women who received supplements of 2.2 g EPA/DHA per day or 4 g EPA/DHA per day. A meta-analysis of fish oil and blood pressure studies found that high-dose (3.7 g/day) fish oil improved blood pressure particularly in hypertensive (BP > 140/90 mm Hg) and older (>45 years) individuals. Dosages less than 500 mg per day did not show an effect.

Omega-3 fatty acids may favorably affect serum and tissue lipid alterations associated with the metabolic syndrome via inhibition of non-esterfied fatty acids, decreased hepatic lipogenesis, decreased TAG synthesis, decreased apo B net production, and increased fat oxidation.

The associations between fish oil and metabolic syndrome also apply to reduced risk of cardiovascular disease. The mechanisms for n-3 fatty acid's protective benefits are not fully understood. In summary, Carpentier suggested that the benefits of n-3 fatty acid supplementation (in those with the metabolic syndrome) might be caused by a reduction of inflammatory conditions, increased cellular antioxidant status, and improved endothelial function.

Omega-3 Fatty Acids, Inflammation, and Inflammatory Diseases

Philip Calder, PhD

Inflammation is mediated through eicosanoids. Eicosanoids are built from 20-carbon LC fatty acids. Inflammatory cells typically contain high proportions of AA and low levels of other 20-carbon fatty acids (EPA), making AA the usual substrate for eicosanoid synthesis.

Consumption of LC n-3 fatty acids (EPA and DHA) results in increased uptake of these fatty acids into cell membrane phospholipid layers. While EPA eicosanoid byproducts are largely biologically inactive, AA stimulates production of active thromboxane A2, prostaglandins, and leukotrienes. Cells with higher DHA and EPA contents, as opposed to AA, produce fewer inflammatory eicosanoids, thus decreasing local and systemic inflammation. In addition, resolvins derived from EPA seem to have an anti-inflammatory effect. Studies have shown associations with n-3 fatty acids related to inflammatory potential and inflammatory cytokines. EPA dosage levels of 2.7 g per day and upward result in a decreased production of PGE 2 , lower dosages show no such decrease. One study supplementing diet with flaxseed or fish oils in humans found a 30% and 74% to 80% decrease in cytokine production, respectively, after 4 weeks of supplementation. Greater benefit of n-3 fatty acids are observed when long-chain n-3 fatty acids are used for supplementation compared to the 18-carbon sources that require enzymes for conversion to LC forms.

Fish oil supplementation has been studied in a number of inflammatory conditions; rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and asthma will be discussed.

Randomized, placebo-controlled, double-blind studies of fish oil and RA have included supplementation levels between 1 and 7 g/day, most around 3.5 g/day with supplementation between 1 and 12 months. Of these studies, 16 of 17 reported improvements in at least 2 clinical outcomes; 6 of 17 studies reported improvement in at least 4 clinical outcomes. Data from meta analyses suggest that there is strong evidence that LC n-3 fatty acids have some clinical benefits in RA with 12 weeks as the common duration of fish oil supplementation for improvements to be observed, the minimum was 3 g EPA and DHA per day.

Randomized, placebo-controlled, double-blind trials of fish oil in IBD have included dosages from 2.7 g to greater than 7 g/day with an average of 4.5 to 5 g/day. Supplementation lasted from 12 to 104 weeks. Seven of 12 studies reported improvement in at least two clinical outcomes; 5 of 12 reported no improvement. Despite several favorable studies meta-analysis data suggest that there is weak evidence that LC n-3 fatty acids have clinical benefits in IBD. However, the apparent ability of LC n-3 fatty acids to sustain the remission of Crohn disease is promising.

Systematic reviews of studies on childhood asthma supplementing between 1 and 6 g/day of LC n-3 fatty acids reached no definitive conclusions.

In summary, there is evidence to support LC n-3 fatty acid supplementation for RA, there is weak support for supplementation for Crohn disease (increase remission length) and no current support for supplementation of patients with asthma. Specifications on the amounts and duration of supplementation have yet to be determined.

Nutrient/Gene Interactions: Where in the Cell Are Omega-3 Fatty Acids Acting?

Richard J. Deckelbaum, MD

Fatty acids can modulate cell lipid metabolism by regulation of sterol regulatory element binding protein (SREBP) in vitro. SREBP affects 11,000 genes as well as membrane cholesterol trafficking and can regulate nuclear receptors, including PPARs and retinoid X receptor (RXR). The mSREBP is a potential target for preventive and therapeutic studies of dyslipidemia, obesity, metabolic syndrome, type 2 diabetes, and hepatic steatohepatitis. Omega-3 and -6 fatty acids can stimulate or repress PPAR transcription depending upon the cellular and experimental milieu. DHA binds to RXR and influence RXR transcription. Fatty acids act as ligands; however, there are many unknowns related to how the genes are regulated and which fatty acids work with which genes. It is clear that there are benefits to dietary n-3 fatty acid intake with most of the studies assessing EPA and DHA together. EPA and DHA appear to have synergistic effects; however, there may be differences in potency depending on where the fatty acids are metabolized. The mechanisms for LC n-3 fatty acid's benefits are only beginning to be understood. It is known that EPA and DHA are situated in cell membranes, and influence signaling pathways, direct DNA interactions, direct protein interactions, transcription factors, receptors, enzymes, scavenger ROA, endoplasmic reticulum-Golgi trafficking, and are metabolized into various eicosanoids.

How Much Omega-3 Fatty Acid is Enough and From Whence Should It Come?

Penny Kris-Etherton, PhD, RD

The adequate intake (AI) for LNA was set as a median intake (without deficiency) to be 1.6 g for males and 1.1 g for females. AIs represent the least amount needed to deter deficiency, but does not take into account disease prevention. Several organizations and expert panels such as the American Heart Association (AHA), Acceptable Macronutrient Distribution Range (AMDR), 2005 dietary guidelines, the National Cholesterol Education Program (NCEP), World Health Organization (WHO), and the International Society for the Study of Fatty Acids and Lipids (ISSFAL) sub-committee have published recommendations for fish and fish oil intake.

Some recommendations are to increase fish intake, while others recommend specific amounts of EPA and DHA either as supplemental or marine sources. Fish with high n-3 fatty acid contents are anchovies, mackerel, salmon, sardines, sea bass, swordfish, and trout. Some of these fish also need to be consumed in limited amounts because of mercury and other toxins. Swordfish, king mackerel, shark, and tilefish should be limited to 7 oz/week; tuna and red snapper should be limited to 14 oz/week; while salmon, catfish, mahi mahi and canned tuna have no restrictions. Water sources have differing toxic levels of mercury, PCBs, digoxins, and others that may alter these general suggestions.

Contrary to other lecturers, Kris-Etherton stated that walnut, flaxseed, soybean, and canola oil can contribute to meeting LNA recommendations. Support for this statement is from the landmark Lyon Diet Heart Study. A Mediterranean style diet would provide approximately 0.6% to 1% energy or 2 g LNA, no more than 7 g per day LA, be rich in oleic acid, poor in saturated fat, and low in n-6 fatty acid sources. The American diet, however, does not mimic these fatty acid intakes and is very high in n-6 fatty acid intake, which hinders the ability for LNA to be converted to EPA and DHA.

Epidemiologic studies in the United States report 500 mg/day of n-3 fatty acids can decrease CHD risk. The average American diet only provides 100 mg EPA and DHA per day. This is 5 times less than the amount observed for cardiovascular benefit and also 5 times less than the WHO's current dietary recommendation for EPA and DHA. Not only are consistent recommendations needed, strategies to increase intakes are also necessary.

Conclusions

Omega-3 fatty acid supplementation during pregnancy causes a probable increase in duration of gestation and birth weight, a possible benefit for those with a history of miscarriages, and a decrease in preterm delivery. However, no reduction in the risk of preeclampsia has been shown.

There is clear evidence that n-3 fatty acids promote improved visual acuity in infants and children when the mother or infant is supplemented with DHA. DHA may be an important nutrient for optimal development throughout gestation and until 2 years of age.

Studies support low DHA as a risk factor for dementia. Low total n-3 fatty acids levels, EPA and DHA associate with greater risk of CVD, dietary intake and/or supplementation is supported as a secondary or tertiary prevention measure. Omega-3 fatty acids also help to prevent type 2 diabetes and the metabolic syndrome, two common precursors to CVD. There is some support for schizophrenia, depressive or aggressive disorders; however, large multi-center clinical trials have yet to be conducted. The anti-inflammatory properties of n-3 fatty acids are helpful in decreasing symptoms of rheumatoid arthritis and may possibly increase remission length in Crohn's patients; however, studies involving asthma and irritable bowel disease have inconsistent results.

Dietary recommendations for n-3 fatty acid supplementation are still a matter of debate. Recommendations may vary depending on desired disease prevention: daily ranges for EPA and DHA begin at 180 mg (for dementia prevention) to 500 mg (decrease in heart disease) to 1000 mg (decrease in mental illness). Marine sources contain EPA and DHA and do not require elongation and desaturation to be effective LC n-3 fatty acids. More research is needed to tease out the conditions in which n-3 fatty acids are beneficial and then to determine the amount and source of n-3 fatty acids needed. Studies are also needed to test the efficacy of increased LNA in diets where there is a coincident reduction in the n6/n3 ratio. At this time, some studies suggest, that LNA sources are not likely to provide clinical benefit.

It is clear that n-3 fatty acids have preventative and therapeutic benefits; however, more research is required to determine the underlying mechanisms, and to develop age and n-3 specific recommendations. Until there is a clear consensus for n-3 recommendations, it appears prudent to ensure intake of the AI for LNA and include marine sources of n-3 fatty acids, via supplementation or fish consumption, throughout the lifespan.

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