For over ten years we’ve pioneered the use of pure EPA for inflammatory regulation in a range of health conditions. Exciting medical research using pure EPA is being conducted all over the world, in conditions ranging from osteoarthritis to Crohn’s disease to colon cancer and it continues to be the focus of our clinical range. Thus, for our therapeutic anti-inflammatory supplements, we have deliberately excluded the other major omega-3 fatty acid DHA from our products. The recent introduction of DHA into our new optimum wellbeing range, MindCare®, highlights an expansion in our approach to omega-3 nutrition.
- Pure EPA is superior for inflammatory control. The competitive relationship between EPA and DHA during digestion and absorption has meant that we’ve always used (and continue to use) pure EPA to target and address inflammation – as it’s simply the most effective treatment method for managing the AA to EPA ratio.
- EPA & DHA are optimal for wellbeing. Since the goal of treatment is to produce significant health improvements, most patients should return to good health. We believe we have a role to play in supporting people through this journey back to health and beyond. Indeed, this reflects our broader philosophy about the role of diet and nutrition in achieving and, crucially, sustaining optimum health. DHA does play an important role in wellbeing, and can be reintroduced in supplement form after the AA to EPA ratio has been addressed and inflammation regulation restored.
- DHA in ethyl-ester form is not stable, whereas DHA in rTG form is stable and has very low oxidation: our supplements have always been used clinically, so concentration and dose are vital factors for our EPA range. Until recently, the only viable form to achieve high concentration, high dose EPA was ethyl-ester. Thanks to improvements in manufacturing technology, re-esterified triglyceride (rTG) oils are now a viable option and these offer tremendous stability and very low oxidation. In certain areas, once inflammatory control is restored with pure EPA, we are including DHA in protocols because we are 100% happy with the stability and low oxidation of DHA in rTG form.
Managing the AA to EPA ratio
A key therapeutic goal of omega-3 supplementation, particularly EPA and DHA from fish oil, is the reduction of inflammation. Evidence clearly supports that for optimal, fast and efficient inflammatory balance to be restored, it is EPA specifically that must be elevated within the cell membranes.
Arachidonic acid (AA) is the primary precursor to the pro-inflammatory eicosanoids that are responsible for initiating and driving the inflammatory process; reducing and inhibiting AA is therefore a necessary intervention to restore inflammatory balance. Whilst EPA and DHA both give rise to anti-inflammatory and inflammatory resolving products, (eicosanoids and docosanoids respectively), it is the eicosanoids produced from EPA that directly antagonise the pro-inflammatory actions of AA and so have the ability to directly reduce AA’s conversion to pro-inflammatory signals.
The unique mechanisms by which EPA directly reduces the availability and conversion of AA (mechanisms not shared by DHA) to pro-inflammatory eicosanoids include:
- inhibition of delta-5 desaturase – the enzyme required for the production of AA
- displacement of AA from the cell membrane
- competition with AA for release from the cell membrane by the enzyme phospholipase A2
- competition with free AA for cyclooxygenase (COX) and lipoxygenase (LOX) enzymes conversion to eicosanoids once released from the cell membrane
Whilst DHA gives rise to anti-inflammatory docosanoids (resolvins and protectins), it is not involved in eicosanoid regulation and so has little impact on the initiation and termination of AA-regulated inflammation compared with EPA.
The use of pure EPA rather than EPA/DHA blends, and the regulation of the AA to EPA ratio for managing inflammatory processes that underlie chronic disease onset and progression, is well established. Restoring optimal EPA levels relative to AA is a proven approach to preventing and treating cardiovascular disease, mental health issues, metabolic disorders, cancer and children’s neurodevelopmental disorders, musculoskeletal issues and general inflammatory disorders. This approach can also be applied as an early intervention for any condition where a high AA to EPA ratio is a predisposing factor and, in particular, when an individual’s AA to EPA ratio is above 3, as identified by a full fatty acid profile test such as the Opti-O-3. Once the imbalances between AA and EPA have been addressed, and inflammatory regulation subsequently restored, the introduction of DHA for long-term maintenance of cell membrane integrity may be advisable for clients who do not consume fish.
The role of DHA in long-term health maintenance
DHA’s unique structure is vital for the fluidity and integrity of all cell membranes. DHA is found in particular abundance in cells whose structure is integral to their function – for example, the brain, retina and CNS. It is for this reason that DHA supply during foetal and early infant development must be maintained. Once these structures are in place, our DHA requirements reduce and a daily DHA intake of 250mg is scientifically established as adequate for replacing the low turnover of DHA that occurs on a daily basis.
Are there detrimental effects in consuming too much DHA?
Consuming too much DHA can be as detrimental as not consuming enough for cell structure and function. Indeed, humans have evolved with a unique feedback mechanism that prevents the over-accumulation of DHA within our cell membranes. When membrane DHA levels are adequate, this results in the down-regulation of the activity of the enzyme delta-6 desaturase. This is the key enzyme involved not only in the conversion of ALA to SDA (the first step in the omega-3 fatty acid pathway), but also in the conversion of EPA to DHA. If we have adequate supplies of DHA, we are adapted to prevent further accumulation (for example, we quite often see studies reporting no rise in DHA levels when pure EPA supplements are consumed). If we consume large amounts of preformed DHA when it is not needed, we also switch off the natural pathway for the production of both EPA and GLA (an anti-inflammatory omega-6), which means that this has the potential to worsen any EPA deficiency and reduce the anti-inflammatory actions of the ‘good’ omega-6 GLA.
So when is DHA supplementation necessary?
Low long-chain omega-3s status is scientifically established as being related to poor health outcomes and increased risk of chronic disease. Average consumption of oily fish (the main source of dietary omega-3) remains well below the recommended one x 140g portion per week, with men and women aged 19 to 64 eating just 52g and 54g, respectively. It is therefore not surprising that raising awareness about omega-3 intake is a top priority for governing health bodies. Biologically, we are able to produce DHA from EPA and so it is not, theoretically, necessary to supplement with DHA, if adequate EPA intake and nutrient status to support healthy enzyme conversion steps is achieved. As modern diets and lifestyle reduce both our enzyme function and nutrient bioavailability, intake of pre-formed DHA from marine foods and grass-fed or pastured animal products is necessary. Average omega-3 intake is very low, however, and recent research investigating the importance of determining baseline omega-3 EPA and DHA levels to understand variations in therapeutic and clinical benefits seen with omega-3 intervention, together with the results from our own Opti-O-3 fatty acid biomarker test, has highlighted the severity of deficiency of both EPA and DHA.
Whilst we know that, for therapeutic intervention, restoring the AA to EPA ratio and subsequently inflammatory regulation, pure EPA is by far the best intervention; for many reasons, too few people actually have the enzyme function and excess EPA status available to produce and protect DHA levels. This means that most people eating a typical ‘Western’ diet are deficient in DHA to some extent before they begin to supplement with EPA, and DHA levels are not fully restored by EPA alone. In our strict determination to remain science-led, we have redefined our view of DHA’s roles. From a long-term health perspective and to ensure that both the AA to EPA ratio and the Omega-3 index – the most validated omega-3 biomarker that tells us the status of EPA and DHA in our cell membranes – are maintained at optimal levels, we believe DHA should be reintroduced at low levels once health and inflammatory control has been restored – although there are some critical caveats to the adjustment in our stance on DHA.
DHA in rTG form enhances bioavailability and reduces PUFA oxidation
Polyunsaturated fats are, by nature, chemically unstable and therefore prone to oxidation. Whilst the oxidation products derived from EPA and DHA exhibit numerous health benefits, in high amounts they have the potential to increase oxidative stress within the body, especially in disease states where antioxidant status or detoxification pathways are compromised. In the natural triglyceride form, the omega-3 fatty acids EPA and DHA are found at the sn-2 (middle) position on the glycerol backbone, where they are protected against oxidation until they are released by lipase enzymes during digestion. Whilst we have always advocated consuming DHA in its natural (fish) state, it is when DHA is removed and concentrated to the ethyl-ester form that potential issues may arise and one of the reasons we have recently revised our opinions on DHA when in rTG form. DHA has 22 carbons and 6 double bonds, making it significantly more unstable than EPA, with its 20 carbons and 5 double bonds. It is therefore the structure of un-esterified DHA that relates to the potential for DHA to generate pro-inflammatory toxic end products such as aldehydes, which can interfere with DNA.
Previous evidence suggested that DHA (particularly when consumed at concentrated and unnecessarily high levels) can, under certain conditions (such as compromised antioxidant status), contribute to increased inflammation, resulting in DNA damage that has the potential to worsen, not protect, our health. Until recently, ethyl-ester was the only viable method of concentrating EPA and DHA in order to deliver the high doses required to exert therapeutic benefits.
Thankfully, due to increased demand for omega-3 supplements over the last decade, advances in manufacturing techniques have resulted in the development of cost-effective technologies that replace the purified ethyl-ester fatty acids back onto a glycerol backbone, recreating the triglyceride structure that would naturally be found in food, thereby dramatically increasing the stability and bioavailability of both EPA and DHA. These advances in manufacturing techniques now allow for affordable, stabilised, re-esterified triglyceride (rTG) omega-3 oils, allowing us to consume concentrated supplemental DHA without risk of high oxidation and any resulting detrimental health outcomes. As such, we are now confidently introducing DHA in rTG omega-3 form into some of our new and existing products that are targeted at supporting and promoting optimum wellbeing, without the stability risk or oxidation concerns associated with using ethyl-ester DHA. The high EPA to DHA ratio of our EPA/DHA blends continues to reflect the importance we place on pure EPA and high-EPA anti-inflammatory protocols. DHA may be introduced to support its lower rate of daily turnover, at levels known to support the integrity of our cell membranes – only made possible through use of the safe and stable re-esterified rTG form.
So what should I give my patients and when?
Pure EPA is now a well established clinical intervention. Studies using pure EPA do so for disease management and treatment. Where inflammation is at the heart of a condition or if a client has not previously supplemented with omega-3, pure EPA is of vital importance to restore the AA to EPA ratio and address inflammatory balance. Depending on the individual, their condition, severity of symptoms, baseline omega-3 levels and response, this intervention period may be 3-6 months only, or may need to be extended to a year or two whilst other lifestyle and dietary factors are addressed, reducing their EPA reliance. Once you and the patient feel their EPA intervention phase is over and their symptoms have improved or are stable, we would recommend including 250mg of DHA daily to support cellular health and the omega-3 index long term.
Even when looking to support and optimise general health during the health maintenance phase, it is still important for EPA to be supplied in abundance and excess of DHA (ideally at least 500 mg of EPA in excess). Daily requirements for DHA are far lower, with 250mg DHA shown to be optimal for healthy adults. Supplementing with EPA and DHA at a ratio of 3:1, after EPA levels have been restored with pure EPA, will support cell membrane integrity and continue to supply EPA at the optimal level required for long-term maintenance of healthy cellular, inflammatory, immune, cardiovascular and neurocognitive functions. In addition, our high strength EPA products provide optimal support for those individuals without pre-existing health conditions who wish to safeguard their long-term health by managing their AA to EPA ratio.