Omega-3

Omega-3 is a nutrient belonging to the lipid- lowering or poly unsaturated fatty acid class.

Omega-3 is also known as marine omega-3s, n- 3 fatty acids, omega 3 fatty acids, omega -3 acid and Omega-3 (n-3) polyunsaturated fatty acids.

Omega-3 fatty acids are vital for maintaining cell structure, production of energy, and support healthy heart, lungs, blood vessel, and immune system function.

Omega-3 deficiency is very uncommon in humans. It may lead to hypoglycaemic characterised by symptoms such as fatigue, dizziness, and headaches.

Omega-3 can be obtained naturally in a variety of protein-rich meals derived from both plant and animal sources. Foods like flaxseeds and flaxseed oil, chia seeds, walnuts, hemp seeds, algal oil (derived from algae, suitable for vegans), soybeans and soybean oilare examples of plant sources, whereas fatty fish (salmon, mackerel, sardines, trout, herring), fish oil supplements, krill oil, cod liver oil and caviar are excellent sources of animal sources of Omega-3.

Omega-3 fatty acids are absorbed largely in the small intestine, distributed throughout the various tissues, and metabolized into active forms. Excess amounts are eliminated from the body through faeces.

The common side effects of Omega-3 include a fishy taste in the mouth, nausea, loose stools, stomach upset, burping and indigestion.

Biochemical action of Omega-3

Omega-3 belonging to the polyunsaturated fatty acid class, acts in several biological processes. It works via glutathione synthesis and redox reactions pathway.

Omega-3 fatty acids, specifically EPA and DHA exhibit an anti-inflammatory properties. Increased EPA or DHA levels have been linked with lower PGE2 and 4-series leukotrienes (LT). In cell membranes, EPA competes with arachidonic acid, resulting in low pro-inflammatory 3-series prostaglandins, thromboxanes, and 5-series leukotrienes. Increased omega-3 levels reduce inflammation by altering leukotriene production. Through the cyclooxygenase and lipoxygenase pathways, EPA and DHA produce resolvins and protectins, which suppress neutrophil migration, TNF, and IL-1 production. They suppress the expression of adhesion molecules and intercellular interactions. Omega-3 PUFAs regulate inflammatory gene expression by acting as peroxisome proliferator-activated receptor gamma ligands. COX-2 expression is induced by PPAR alpha activation. Triglycerides are reduced by EPA and DHA through inhibiting acyl-CoA:1,2-diacylglycerol acyltransferase, increasing liver beta-oxidation, lowering lipogenesis, and inhibiting esterification. Their distinct features result in anti-inflammatory and lipid-modulating actions.

Volume of distribution of EPA is approximately 82L

In a compartmental study, approximate half-life of ALA, EPA and DHA are 1h, 39-67h and 20h, respectively.

Clearance rate of EPA is approximately 757mL/h.

Omega 3 is available in capsules and oral solutions.

• Capsules: To be swallowed whole with water/liquid, as applicable.

• Oral liquid solutions: To be taken by mouth, as applicable.

Omega 3 can be used as a supplement when the amount of omega 3 taken through diet is insufficient.

Taking omega 3 supplements effectively treats deficiency caused by inadequate intake of omega 3.

Omega 3 supplements may reduce the risk of heart disease by lowering triglycerides, reducing blood pressure, and prevention of plague formation in the arteries.

Supplemental omega-3 may help cognitive function and lower the risk of neurodegenerative illnesses like Alzheimer's.

Omega 3 supplements might provide anti-inflammatory benefits that are helpful for diseases including arthritis and inflammatory bowel disease.

Vitamins and natural supplements should not replace a balanced diet.

This product is not intended to diagnose, treat or prevent any disease(s).

Omega 3 can help to support as a supplement for the following health benefits:

• Cardiovascular disease (CVD)- Numerous studies show the cardiovascular advantages of including fatty fish and seafood in a balanced diet. These foods efficiently lower triglyceride levels because they are high in EPA and DHA. The American Cardiac Association (AHA) recommends eating seafood frequently, usually one to two servings per week, to reduce cardiac problems, especially when substituting more heart-healthy options. The AHA advises a daily consumption of around 1 g of EPA and DHA for people with pre-existing cardiac problems, ideally from oily fish, with supplements as a reasonable alternative when under medical care. However, the AHA does not recommend omega-3 supplementation for people with minimal cardiovascular risk.
• Prior to cardiac surgery- Months of -3 fatty acid supplementation are required in the majority of studies for secondary CHD prevention before any positive effects are discovered. An investigation including individuals who had cardiothoracic surgery, however, revealed immediate benefits within a few weeks.
• Neurological effects- There is evidence that some neurological illnesses are associated with changes in the metabolism of -3 fatty acids and serum phospholipid composition. Epidemiological research has linked low plasma DHA levels to diseases including schizophrenia, ADHD, dyslexia, personality problems, depression, and bipolar disorder. There is subsequently increasing interest in research into how omega-3 fatty acid supplements affect neurological development, cognitive function, behaviour, and associated diseases.
• Age-related macular degeneration (AMD)- In older people, age-related macular degeneration (AMD) is the main factor that causes loss of vision. Increasing the omega-3 intake through food may lower the risk of developing AMD. Omega-3 supplements, however, are ineffective at slowing the onset of AMD or protecting eyesight once the condition has already set in.
  

• Alzheimer’s disease, dementia, and cognitive function- According to some study, eating foods high in omega-3 fatty acids, such as fish, may lower your chance of developing dementia, Alzheimer's, and other cognitive problems. To completely understand how omega-3 fatty acids affect brain function, further research is needed.

Omega 3 supplementation may be administered orally.

Orally: Omega 3 supplements are available as capsules and oral solutions that can be taken orally. It is recommended to swallow the capsules whole and not to chew, crush, break, or dissolve and to take it alongside a meal or following a meal so as to maximise its absorption.

The patient shouldn't take a double dose if it is due for their next capsule and should take the missing dose as soon as they remember it.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional).

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Capsules: 300 mg, 900 mg, 1000 mg, 1200 mg, 1250 mg, 1400 mg,
• Liquids, oral: 4 fl oz (119 ml), 8 oz (1270 mg), 8.4 oz (1100 mg)

Dosage Adjustment for Adult Patients

Hypertriglyceridemia (≥ 500 mg/dl) as an adjunct to diet and exercise are as follows:

Administer icosapent ethyl capsules everyday with a dose of 4 g/day taken as two 2g capsules BID with foods.

Administer Omega-3-acid ethyl esters capsules everyday with a dose of 4 g/day taken as 4 capsules/day with meals or two capsules BID with foods.

Administer Omega-3-carboxylic acids capsules everyday with a dose of 2 g/day taken as 2 capsules/day or 4 g/day taken as 4 capsules/day. Clinical trial administration was without regard to meals.

Administer Omega-3-acid ethyl esters A capsules everyday with a dose of 4 g/day taken as 4 capsules/day with meals or two capsules BID with meals.

Omega 3 should be a supplement that helps in several biochemical processes and appropriate dietary restrictions.

• Avoid alcoholic beverages.
• Stay within your daily calorie needs.
• Avoid foods and beverages like processed and fried foods, high in fat, sugar, or cholesterol, as it may hinder its absorption and effectiveness.
• Limiting meals high in omega-6 fatty acids is advised while taking omega-3 supplements since an imbalance between omega-3 and omega-6 consumption might happen.

Recommended Daily Allowance (RDA)

As per FSSAI, the estimated RDA of Omega is not established

Upper Tolerable Intake (UTL):

The UTL of Omega 3 is not established.

Omega 3 supplementation may be contraindicated in the following conditions:

• Hypersensitivity: sensitive to fish-related allergies or seafood
• Chronic liver disease
• Chronic kidney disease (CKD)
• Kidney failure
• Dyslipidemia
• Active bleeding disorders

Omega 3 supplementation is generally safe and well tolerated.

The adverse reactions related to Omega 3 can be categorized as:

• Common: GI disturbances like diarrhea, nausea, and indigestion.
• Less Common: Allergic reactions and fishy aftertaste or burps
• Rare: Bleeding, low blood pressure, suppress immune system and liver problems.

The clinically relevant drug interactions of omega 3 are summarized here:

• Antiplatelet drugs- Using this medication combined with antiplatelet medicines might increase the risk of bleeding. However, numerous clinical trials have not demonstrated any significant influence on bleeding. One research suggested possible advantages, with no predicted specific interactions at recommended therapeutic levels.
• Anticoagulant drugs- Clinical studies involving surgical patients receiving warfarin simultaneously have not found a significant rise in bleeding events. However, one clinical research found that extremely high levels of 12 g/day induced longer bleeding times. Therapeutic dosages often fall below this limit, indicating safety in this population. However, care should be used, and dosages more significant than 12 g should only be given under medical supervision to avoid any adverse effects.
• Non-steroidal anti-inflammatory drug- Theoretically, concurrent use of fish oil supplements may have anti-inflammatory effects, indicating a positive interaction. Adjustments to drug dose may be necessary.
• Pravastatin- According to one clinical study, low-dose pravastatin mixed with fish oil supplementation is better than pravastatin alone for improving the lipid profile after kidney transplantation — possible beneficial interaction.
• Contraceptive drugs- Birth control pills might reduce the drug's effect if taken with omega 3. It is recommended to separate the doses.

The common side of omega 3 includes the following:

• Fishy taste in the mouth
• Loose stools
• Burping
• Indigestion.
• Fishy breathe
• Gas
• Upset stomach
• Nausea
• Halitosis
• The fishy odour of the skin and urine

Omega 3 supplements should be prudent in the following group of special populations.

• Pregnancy: For the development of the foetal brain and eyes during pregnancy, omega-3 fatty acids are required. They may boost the mother and baby's general health and reduce the risk of premature birth.

The recommended adequate intake for pregnant mothers is 1.4 g.

• Paediatrics: Omega-3 fatty acids are essential for the growth and development of children. They promote the brain and visual development of infants and children. Omega-3s may also lower the risk of childhood allergies and help manage diseases like attention deficit hyperactivity disorder (ADHD). It is recommended that children should take supplements or consume enough omega-3s through food whenever required.

The recommended adequate intake for paediatric ranges from 0.5 to 1.1 g.

Dosage Adjustment for Paediatric Patients

There are no specific dosage adjustments provided.

• Geriatrics: The elderly may benefit from including sources of omega-3 fatty acids in their diet or from supplementing with it. Omega-3 fatty acids are beneficial for elderly people as they have a number of health advantages. It can help lessen joint discomfort caused by illnesses like arthritis, lower the risk of heart disease, and improve cognitive performance. In addition to improving eye health, omega-3 fatty acids may reduce the incidence of age-related macular degeneration.

The recommended adequate intake for geriatrics is 1.6 g for males and 1.1 for females.

• Lactating mothers: DHA and other omega-3 fatty acids are especially important for nursing women since they enhance breast milk production and help in the development of the foetus. While nursing, getting enough omega-3 fatty acids can benefit both the mother's and the infant's health.

The recommended adequate intake for lactating mothers is 1.3 g

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

Biochemistry profile of Omega-3

Omega-3 fatty acids (OM3FAs) are polyunsaturated fatty acids with a long hydrocarbon chain with a carboxylic acid group (COOH) at one end, with at least one double bond between the third and fourth omega-end carbon. The three most common clinically omega-3 polyunsaturated fatty acids (PUFAs) are α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

Omega-3 fatty acids have several important roles to play in the body. They affect the permeability and stability of cell membranes as they are vital components of the membrane. Cell signalling, receptor performance, and the control of gene expression are all impacted by this. Particularly, EPA and DHA are recognized for their anti-inflammatory capabilities, which regulate the formation of pro-inflammatory molecules and help in the overall management of inflammation.

In addition, omega-3 fatty acids are very beneficial for the heart. They help with lowering triglycerides, lowering blood pressure, and preventing blood clots. They also improve cognitive function and may reduce the risk of neurodegenerative disorders, contributing to brain health.

Kinetic profile:

• Absorption: With the help of bile acids and pancreatic enzymes, omega-3 fatty acids are absorbed primarily from the small intestine. Once absorbed, it is incorporated into chylomicrons, lipoprotein particles that transport dietary fats through the lymphatic system and finally reach the bloodstream.
• Distribution: Omega-3 fatty acids are distributed widely throughout the body, with the highest concentration in cell membranes, specifically in the brain, retina, and heart.
• Metabolism: Omega-3 fatty acids go through several metabolic pathways and are converted to active forms like alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA, DHA, and EPA are metabolized and degraded in the liver, also the site of n-3 fatty acid intermediate production. This forms VLDL, which transports fatty acids from the plasma to tissues. Lipoxygenases and cyclooxygenase are two significant enzymes that produce lipid signalling molecules from EPA, DHA, and ALA.
• Elimination: Excess omega-3 fatty acids that are not utilized are finally eliminated from the body via faeces.

1. https://www.fssai.gov.in/upload/advisories/2021/07/60f1798019f94Direction_RDA_16_07_2021.pdf
2. Braun L, Cohen M. October 1, 2014.Herbs and Natural Supplements; 4th Edition Vol-2. Australia. Elsevier.
3. Nagao K., Yanagita T. Conjugated fatty acids in food and their health benefits. J. Biosci. Bioeng. 2005;100:152–157. doi: 10.1263/jbb.100.152.
4. https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/

5. Institute of Medicine, Food and Nutrition Board. Dietary reference intakes for energy, carbohydrate, fibre, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients). Washington, DC: National Academy Press; 2005.
6. https://ods.od.nih.gov/factsheets/Omega3FattyAcids-Consumer/