Name: Omega3 fatty acids, Eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA), Fish oil
Goes well with: Turmeric (Curcumin), Vitamin D
Number of scientific references: 76
Level of Evidence: Level III What is this?
Note: Multiple studies in humans have confirmed that omega-3 fatty acids as an adjunctive therapy help in bipolar disorder. They help rectify existing deficiency and optimise fluidity in brain cells to balance brain chemistry and stabilise mood. They also protect metabolic health in bipolar disorder and can aid in the prevention of mood disorders.
Including polyunsaturated fatty acids in our diet has been emphasised upon over and over again by nutritionists and researchers. Not all saturated fats are bad, but there is a balance to be achieved.
Among the polyunsaturated fatty acids, they are omega-6 and omega-3, and their ratio can have significant health impacts if not maintained. The omega-6 to omega-3 ratio was hypothesised to be 1:1 during human evolution but now it has shifted to 10:1 to 20-25:1.
We can’t synthesise all fatty acids as we lack certain enzymes required for their synthesis and interconversion. Both omega-6 and omega-3 have to be derived from the diet.
Alpha-linolenic acid (an omega-3 fatty acid) is the precursor of other omega-3 fatty acids while linoleic acid is the precursor of omega-6 fatty acids.
Eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are long chain omega-3 fatty acids. DHA is the most abundant polyunsaturated fatty acid in the cell membrane of neurons. EPA aids in the production of anti-inflammatory agents.
The conversion of ALA to EPA is around 5% while conversion rate to DHA is less than 0.5%. And that’s why we need to include omega-3s in our diet.
When it comes to brain health, omega-3s play three important roles:
- Supporting survival, structure and development of different cells in the brain
- Regulating inflammation in the brain
- Regulating the brain chemistry
Omega-3 fatty acid supplements benefit in bipolar disorder as natural mood stabilisers. They help overcome the existing deficiency and also reduce inflammation in the brain. They regulate and normalise the abnormalities in the structure of brain cells in bipolar disorder thus relieving mania and depressive symptoms.
Suggested Omega-3 Supplements For Bipolar Disorder
Please consult a health practitioner before taking any health supplements.
As per clinical studies on mood disorders, an omega-3 supplement offering a higher quantity of EPA than DHA is advised.
Also, since you need a higher dose of omega-3s for a clinically relevant effect you should look for pure and concentrated omega-3s. These provide more omega-3s per capsule so you don’t land up consuming many capsules to meet the recommended doses.
I have listed a few quality supplements with concentrated omega-3 fatty acids.
Dosage: 1-2g of omega-3 per day. Please read the detailed dosage section below and discuss with your doctor to find an optimal dose for you.
|WHC UnoCardio 1000||Nordic Naturals EPA||Nordic Naturals Algae Omega|
Image Credit:Nordic Naturals
Image Credit:Nordic Naturals
|Provides 652 mg EPA and 440mg DHA for 1280 mg omega-3 (1 capsule)
Contains additional vitamin D (cholecalciferol)
(Consume Vitamin D containing supplements only in case of Vit D deficiency/insufficiency)
|Provides 850 mg EPA and 200mg DHA for 1210-1230 mg omega-3 (1 capsule)||Provides 195 mg EPA and 390 mg DHA per 715 mg omega-3 (2 capsules)
Vegetarian omega-3 derived from algal oil
|Buy from Amazon (US, UK)||Buy from Amazon (US, UK, Canada)
Buy from iHerb (Global)
|Buy from Amazon (US, UK, Canada)
Buy from iHerb (Global)
7 Proven Benefits Of Omega-3 Fatty Acids For Bipolar Disorder
Let’s explore the research studies that prove the benefits of omega-3s in bipolar disorder.
1.Omega-3 fatty acid supplementation may reduce the deficiency of EPA and DHA in bipolar disorder
Table of Contents
- 1 Suggested Omega-3 Supplements For Bipolar Disorder
- 2 7 Proven Benefits Of Omega-3 Fatty Acids For Bipolar Disorder
- 2.1 1.Omega-3 fatty acid supplementation may reduce the deficiency of EPA and DHA in bipolar disorder
- 2.2 2.It acts on a cellular level to protect neurons and stabilise mood
- 2.3 3.Omega-3 fatty acids help stabilise mood in bipolar disorder
- 2.4 4.They help reduce symptoms of depressive phase in bipolar disorder
- 2.5 5.They help reduce inflammation in the brain
- 2.6 6.Omega-3s are neuroprotective agents and boost cognition
- 2.7 7.They can protect metabolic and heart health in bipolar disorder
- 3 Dosage of Omega-3 Fatty Acids For Bipolar Disorder
- 4 Precautions with Omega-3 Use
- 5 Conclusion
Researchers from University Of Cincinnati College of Medicine, USA found that 75% of the patients with treatment-resistant mood disorders had omega three fatty acid deficiency. This was significantly higher than the rates observed in general population which is around 25%.
Membranes surrounding our red blood cells contain EPA and DHA and this indicative of omega-3 fatty acid status. A study (Psychiatry Research,2015) suggests that first episode bipolar disorder is associated with reduced DHA levels in the red blood cells.
A recent meta-analysis study also confirms that patients with bipolar I disorder have DHA deficits in the red blood cells. Sublette et al. have found that low EPA levels in susceptible individuals are associated with severity of mania.
Low EPA and DHA levels may be responsible for initial development of mania and increase risk of developing bipolar disorder (Early Intervention In Psychiatry, 2016)
Multiple studies have also proven that bipolar disorder patients have altered fatty acid metabolism. A deficit in fatty acid metabolism and enzymes involved in it may also be related to personality traits such as neuroticism, depression, suicidal risk and reduced ability to function.
Sobczak and colleagues from Maastricht University, Netherlands have reported that first degree relatives of bipolar disorder patients have altered cholesterol and fatty acid levels; they have higher omega six fatty acid levels, and these correlate impaired serotonin action.
The experts in organic chemistry must be aware of the process called esterification. This process is essential when we are considering the uptake of fatty acids by the brain.
To keep things simple for the rest of us, esterification is a method by which our body metabolises polyunsaturated fatty acids. So that gives us esterified, and unesterified forms of fatty acids; the unesterified form of polyunsaturated fatty acids cross the blood-brain barrier more readily than the esterified forms.
A study published in Bipolar Disorders, 2015 revealed that patients with bipolar disorder had a lower ratio of unesterified to esterified EPA which made them vulnerable to mood disturbances. It was also observed that panic attacks were associated with lower omega-3 fatty acids and higher omega-6 fatty acids levels.
Studies conducted on brain tissue of bipolar disorder patients have revealed mixed results: some indicate omega three fatty acid deficiency, some have observed altered lipid metabolism in case of omega six fatty acids while some report no disturbances in fatty acid levels in certain parts of the brain.
Here is what we can gather from these scientific studies:
- Patients with bipolar disorder have omega-3 fatty acid deficiency
- This deficiency in omega-3 fatty acid may correlate with the first episode, mania, depression, and panic attack like symptoms.
- Lipid metabolism is altered in bipolar disorder and this evidenced by reduced function of enzymes that are involved in this process. The altered metabolism could be of omega-6 as well as omega-3
- There may be a genetic link involved in this altered lipid metabolism.
- Reduced dietary intake of omega-3 and increase in dietary omega-6 and trans-fat could be responsible for the deficiency as well.
Quick Gist: Research has confirmed that bipolar disorder patients have omega-3 fatty acid deficiency and altered lipid metabolism. These deficits correlate with mood disturbances such as mania and panic attacks and even suicidal risk.
Supplementation with omega-3 fatty acids as well as a reduction in dietary omega six fatty acids can reduce symptoms of bipolar disorder and improve the therapeutic efficacy of conventional medications.
2.It acts on a cellular level to protect neurons and stabilise mood
Apart from the metabolic and brain structure related abnormalities observed in bipolar disorder, certain changes are observed at a cellular level in the patients.
Receptors are proteins that receive multiple substances including neurotransmitters and their interaction bring about subsequent biological reactions. These receptors are present in the outer cell membranes of neurons.
They are like the locks which prevent unwanted substances from entering the cells, but when the right key approaches them (in this case it is a neurotransmitter), they attach to each other and allow the key or signalling substance to enter the cell.
Cellular signals are first received by these receptors or protein complexes at the outer membrane and then transferred to the cell. This process is known as signal transduction, and these processes are deranged in bipolar disorder.
Abnormalities in these systems contribute to disturbed brain chemistry and hence lead to mood cycling.
Some of the signal transduction systems that are found to have abnormalities in bipolar disorder are G proteins, protein kinase C and phosphatidylinositol.
Conventional medications partially fix these abnormalities. Similarly, omega-3 fatty acids also act as mood stabilisers by normalising these cellular abnormalities.
EPA and DHA help in normalising these cellular abnormalities in the following ways:
- These essential fatty acids contribute to the natural structure phospholipids or fats present in the cell membrane. This helps maintain cell integrity.
- They modulate activities of proteins present in the cell membrane.
- They contribute to the fluidity of the cellular membrane; they are loosely packed in the cellular membrane and create a fluid-like matrix.
- They inhibit the activity of signal transduction system protein kinase
- They inhibit excess calcium from entering the cells. (Studies on platelets suggest that there is an increase in calcium release in cells during different mood states in bipolar disorder.)
Thus, apart from rectifying deficiency, omega-3 fatty acid supplementation may help normalise cell structures and their signalling systems as a part of their mood stabilising effect.
Quick Gist: Research studies that various aspects of cell signalling and cell membrane structure are altered in bipolar disorder. These alterations affect regulation of neurotransmitter levels and thereby affect mood.
Omega-3 fatty acids contribute to the natural structure of the fats present in cell membranes and thus protect the integrity of the cell. As mood stabilisers, they help to normalise the cell signalling systems in bipolar disorder.
3.Omega-3 fatty acids help stabilise mood in bipolar disorder
Based on positive results from empirical evidence, multiple research studies have been conducted in humans to ascertain the effects of omega-3 fatty acids supplements in bipolar disorder.
Here is a tabulated form of a few clinical trials that have observed positive effects of omega3s as a mood stabiliser.
|Author||Number of patients||Dosage and Therapy Duration||Findings of the study|
|Stoll et al. (1999)||30 patients with bipolar disorder||9.6g of omega3 per day for four months||Omega3 improved all aspects of the disorder better than placebo. Patients in the omega3 group had a longer period of remission.|
|Sagduyu et al.(2005)||37 patients with bipolar disorder and were taking standard treatment||1-2g of omega3 fatty acid per day||Omega3 in addition to standard therapy helped reduce irritability|
|Osher et al. (2005)||12 patients with bipolar I disorder and depressive symptoms||1.5-2g of EPA per day for six months||8 out of 10 patients completed one month of the follow-up; 50% or greater reduction in depressive symptoms was observed.
No patient developed hypomania or mania, and no side effects were observed
|Frangou et al. (2006)||Patients with bipolar disorder and depressive symptoms||1-2g of ethyl-EPA per day for 12 weeks||Significant reduction in depressive symptoms was observed; omega3 was found to be safe and effective as an add-on therapy for bipolar disorder|
|Clayton et al. (2009)||18 patients with paediatric bipolar disorder||360mg EPA and 1560mg DHA per day for six months||Both clinicians and patients observed improvement in mania and depressive symptoms in children after omega3 supplementation|
|Gracious et al. (2010)||Patients with paediatric bipolar disorder||Flax oil capsules containing 550 mg alpha-linolenic acid for every 1g||Researchers found that flax oil may reduce disease severity in children with bipolar disorder but fish oil therapy is more favourable.|
|Wozniak et.al (2015)||24 Patients with Paediatric bipolar spectrum disorders||Omega3 and Inositol combination or individual therapy for 12 weeks||54% completed the study. Combination of omega3 and inositol reduced mania and depressive symptoms better than individual therapies|
|Fristad et al. (2015)||23 individuals with the subsyndromal bipolar disorder (7-14 years of age)||2000mg of omega3 per day for 12 weeks in addition to psychoeducational psychotherapy; patients were on conventional meds for ADHD and sleep||83% completed the study. Significant improvement in depressive symptoms was observed. Mania improved with time. The effect of omega3 was moderate.|
|Shakeri et al. (2016)||100 patients with bipolar I disorder and taking standard meds||1000mg of omega3 per day for three months||Significant reduction in severity and intensity of mania was observed.|
|Vesco et al. (2017)||95 patients with bipolar disorder and depression||1.87g of omega three alone or in combination with psychoeducational psychotherapy for 12 weeks||Omega 3 therapy alone or combined improved cognition and ability to regulate behaviour.
Individuals with ADHD experienced slightly better benefits with omega3s.
These research studies demonstrate that omega-3 fatty acid supplements at a dose of 1-2g per day are beneficial as an add-on therapy in bipolar disorder. They can help reduce mania and depressive symptoms.
Omega-3 may also serve beneficial as a monotherapy or in combination with psychotherapy in juvenile bipolar disorder. They may aid in the prevention of mood disorders in children and adolescents.
Most studies mentioned above have used omega-3 fatty acids as an add-on to standard medications for bipolar disorder. This is indicative of the safety of the combination treatment, but experimental studies have also been conducted to know whether it is safe to take omega-3 when taking prescribed medicines for bipolar disorder.
Arachidonic acid cascade in the brain is one of the first steps involved in inflammation, and its dysregulation also contributes to mania. Drugs used to treat mania such as lithium, valproate, carbamazepine; clozapine is proven to regulate this pathway and inhibit inflammation in the brain.
Similarly, omega-3 fatty acids and polyunsaturated fatty acids in diet regulate the arachidonic pathway to relieve inflammation in the brain and reduce mood disturbances. Research studies published in Molecular Neurobiology, 2017 showed that omega-3 fatty acids when combined with lithium and valproate prevent and reverse mania, reduce oxidative stress and regulate energy metabolism in the brain.
These research studies confirm that it is safe to take omega-3 fatty acids when taking mood stabilisers for bipolar disorder.
Quick Gist: Omega-3 fatty acid supplements serve as mood stabilisers in children as well as adults with bipolar disorder. A dose of 1-2g per day with a higher percentage of EPA is proven to be beneficial.
4.They help reduce symptoms of depressive phase in bipolar disorder
In 1996, Adams et al. after studying patients with moderate to severe depression proposed that nutritional strategies aimed at reducing arachidonic acid and the eicosapentaenoic acid ratio can help reduce depression severity.
Omega-3 fatty acids benefit in depression by interacting with serotonin and dopamine transmission, interacting with HPA axis (a network of the brain and hormone-secreting glands that is involved in stress), reducing inflammation in the brain etc.
Meta-analysis studies are assessing clinical trials conducted on omega-3 for depression report that omega-3s as an adjunct therapy is effective in patients with depression. Supplements containing more than 60% EPA in the EPA and DHA combination are more effective; the dose range is 200-2000mg per day.
One study reports that omega-3 fatty acids may be more beneficial in depressive phase rather than mania phase in bipolar I disorder.
12 patients with bipolar I disorder with depressive symptoms were treated with 1.5 to 2g of EPA per day for six months. Eight out of ten patients had 50% or greater reduction in depressive symptoms within one month. No patient developed hypomania or mania-like symptoms.
Quick Gist: Omega-3 fatty acid supplementation is proven to reduce depressive symptoms at a dose of 200-2000mg per day. EPA supplements may help as an add-on therapy in bipolar depression.
5.They help reduce inflammation in the brain
When discussing the causes of bipolar disorder, I have mentioned how inflammation worsens brain health and mood.
Low EPA and DHA levels and a high ratio of omega-6 to omega-3 fatty acids contribute to increased levels of inflammatory agents such as eicosanoids and cytokines. This state of inflammation increases the risk of developing mood disturbances
Chronic inflammation can contribute to immune dysfunction and pave the way for other medical conditions that may occur concurrently with bipolar disorders.
Recent review studies have confirmed that omega-3 fatty acids may serve as potential anti-inflammatory agents and as an add-on therapy, they may even have a moderate antidepressant effect in bipolar depression.
Omega-3 fatty acids are natural anti-inflammatory agents and produce inflammation resolving agents in the body.
Research proves that omega-3 fatty acid supplementation can benefit as a monotherapy or adjunct therapy in bipolar disorder and major depressive disorder. This is partially attributed to their anti-inflammatory effect.
Quick Gist: Low omega-3 fatty acids levels increase the level of circulating inflammatory agents and leads to immune dysfunction. Supplementation with EPA and DHA can help reduce inflammation in bipolar disorder and reduction in inflammation may also contribute to an antidepressant effect.
6.Omega-3s are neuroprotective agents and boost cognition
Omega-3 fatty acids mediate neuroprotection by protecting cell membranes of brain cells and providing energy. They aid in the maintenance of brain health and also support repair in case of injury.
A review study published in Frontiers in ageing neuroscience, 2015 highlights the different roles of independent omega-3 fatty acids in neuroprotection. As per the review, EPA has been found beneficial in mood disorders while DHA may be of help in neurodegenerative conditions like Alzheimer’s.
The ability of long-chain omega3s to regulate immunity and inflammation helps stabilise mood and protect brain health.
DHA deficiency reduces Brain-Derived Neurotrophic Factor levels, and this has been observed in bipolar disorder as well.
Brain Derived Neurotrophic Factor is a protein that supports the growth of new neurons. It plays an important role in neurogenesis and neuroplasticity. Supplementation with omega3s may normalise the levels of this protein and restore healthy brain structure and function.
Frangou et al. observed that omega-3 fatty acid supplementation in bipolar disorder patients led to a significant rise in N-acetylaspartate levels in the brain. N-acetylaspartate is an amino acid present in the brain, and it has the highest concentration of all free amino acids.
Although it’s function has not been clearly understood yet, previous research indicates that it may be involved in energy metabolism, neurotransmitter regulation and development of myelin.
Frangou and colleagues hypothesise that this rise in NAA levels may be linked with the development of new brain tissue. This suggests that omega-3s mediate a neuroprotective action in bipolar disorder.
Cognitive function is our ability to think, reason, retain memory, solve problems etc. Mood disorders may cause cognitive dysfunction. Omega-3 fatty acid supplements are identified as potential cognitive enhancers in such mood disorders including bipolar disorder.
In fact, an ecological study reported that greater seafood consumption is associated with lower lifetime prevalence rate of bipolar disorder.
Quick Gist: Omega-3 fatty acids are essential for brain health. They are a vital constituent of cell membranes of neurons. They also participate in the brain’s energy metabolism process.
They aid in maintenance and repair of brain structure and function. Hence their supplementation can help the brain recover from damage occurring in mood disorders and also function as cognitive enhancers in bipolar disorder.
7.They can protect metabolic and heart health in bipolar disorder
Metabolic syndrome is a group of conditions affecting the metabolic health such as high cholesterol, blood pressures issues, abdominal obesity, insulin resistance etc.
A study published in The American Journal of Psychiatry, 2013 suggests that overall metabolic syndrome rate is 37.3% in bipolar disorder patients involved in studies that were reviewed.
In comparison to the general population, patients with bipolar disorder had higher metabolic syndrome rates. Metabolic syndrome was more prevalent in patients taking antipsychotics than those that were drug-free.
Antipsychotic use is associated with abnormalities in metabolic health such as high triglyceride levels (these indicate levels of certain fats in the blood, and in case of abnormality this is indicative of increased risk of heart disease).
Researchers from Tehran University of Medical Sciences, Iran conducted a study where patients taking antipsychotics and mood stabilisers were treated with less than 1g of omega-3 per day.
Modest improvement in certain cardiovascular risk factors was observed such as those parameters affecting coagulant status and lipid levels.
Previously they had observed that addition of omega-3 to the therapy involving mood stabilisers like lithium and sodium valproate and antipsychotics like olanzapine, brought about modest reductions in insulin levels.
Quick Gist: Bipolar disorder patients are at an increased risk of developing heart diseases and metabolic disturbances. Use of antipsychotics and mood stabilisers can impair metabolic health.
Addition of omega-3s as an add-on therapy can prevent such metabolic disturbances and protect heart health in bipolar disorder.
Dosage of Omega-3 Fatty Acids For Bipolar Disorder
The dose of omega-3 fatty acids for bipolar disorder, as evaluated by research studies, is 1-2g per day. Research suggests that the supplements should preferably have a higher proportion of EPA than DHA.
The duration of the therapy should be around 8-12 weeks to observe the benefits of omega-3s in bipolar disorder.
You could also consider including dietary sources of omega-3s. Seafood like trout, sardine, mackerel, salmon, herring, anchovy is rich sources. Vegetarian sources include seeds, nuts and wild plants and they mostly contain ALA. Walnuts, flaxseed, sesame and algal oil are a few vegetarian sources.
Please consult a health practitioner before taking omega-3 supplements for bipolar disorder.
Precautions with Omega-3 Use
One of the most common issues with omega-3s is gastric discomfort and fishy aftertaste. Start with small doses and increase gradually. Also, consume them after meals to avoid belching.
In case of seafood allergies, avoid fish oil.
High dose omega-3s can have anti-platelet activity; avoid in case you are taking blood thinners or if you have a bleeding disorder.
Omega-3s may have drug interactions with blood thinners, NSAIDs, steroids, cyclosporine, diabetes medications and cholesterol-lowering drugs. Maintain a 3-4 hour gap between taking omega-3s and conventional medicines.
Ensure that you get good quality omega-3 capsules that are free from heavy metal and other contamination. Consult your doctor before taking omega-3 supplements.
Multiple studies conducted in humans, as well as authoritative meta-analysis and review studies, have confirmed that omega-3 fatty acid supplements are beneficial in bipolar disorder treatment.
They are proven to reduce mania and depression. They mediate this therapeutic effect by rectifying deficiency and reducing inflammation in the brain.
Certain abnormalities are observed in brain cells in bipolar disorder, and omega-3 supplements help ameliorate these abnormalities and in turn regulate brain chemistry favourably.
Apart from reasons related to the study design that is responsible for such discrepancy, there is one very interesting point highlighted by Saunders and colleagues.
They state that despite supplementing with omega-3s is not enough; one needs to reduce dietary omega-6 fatty acids to observe the benefits of omega-3 supplements. Concurrent reduction in omega-6 and supplementation with omega-3 will deliver therapeutic effect in bipolar disorder.
So that would involve cutting down on vegetable oils like soybean oil, canola oil, corn oil, hydrogenated fats and processed foods. Olive oil and coconut oil are rich in good fats. Grass-fed meat sources are rich in healthy omega-6s.
Which source of omega-3 do you rely on and how has it helped you in bipolar disorder? Do leave your comments below.