With rates of obesity still on the rise and showing no sign of slowing, successful dietary interventions are necessary to protect against the associated burden of chronic illness. Taking omega-3s is one intervention with extremely high potential for preventing and reversing the complications associated with the high inflammatory load underpinning many obesity-related complications; however, with research linking obesity with excessive oxidative stress, and the wave of studies showing oxidative stress may be to blame for many negative omega-3 study outcomes, perhaps serving up platters of highly purified omega-3 oils to our overweight clients may, in fact, be fanning the flames of inflammation and adding to the problem, not aiding it. It is increasingly clear that the need to determine the status of the ‘environment’ for nutritional interventions, and ensuring correct dosage to achieve the desired health benefits, are key to success.
Inflammation and obesity – it’s what’s inside that counts.
Obesity is a major public health problem with 60% of adults and 30% of children in the UK currently estimated as overweight or obese. Whilst body mass index (BMI) is the routine measurement used to estimate obesity, it fails to report body composition, or the location of the excess fat. Waist to hip ratio (WHR), in contrast, is more reflective of central obesity and the presence of visceral fat, which differs from ‘standard’ fat by acting as a reservoir for inflammatory white blood cells. Excess visceral fat mass is a known risk factor for poor health due to its production of a number of pro-inflammatory molecules that trigger a series of autoimmune reactions, leading to long-term health complications, such as insulin insensitivity. Interestingly, normal weight central obesity (as defined by WHR) is associated with higher mortality than BMI-defined obesity,  and central obesity, in combination with insulin resistance, hyperglycaemia, hypertriglyceridaemia, hypertension and fatty liver – collectively metabolic syndrome – increase the risk of developing health conditions including type II diabetes and cardiovascular disease. Whilst it is well established that dietary and lifestyle changes help prevent and manage obesity, recent evidence suggests that insulin resistance, as a consequence of obesity, and particularly central adiposity, may be preventable by adopting dietary approaches that modulate inflammation.
The omega-3 panacea
A low omega-3 index (cellular EPA & DHA), coupled with a high AA to EPA ratio (inflammatory balance biomarker) is associated with obesity, insulin resistance and metabolic syndrome through the promotion of low-grade chronic inflammation; [1,2] as such, increasing omega-3 levels can reduce the inflammatory burden that drives metabolic syndrome.  Studies show that omega-3 status is highly compromised in children and adults with obesity and insulin resistance, and that omega-3 has the ability to prevent and correct metabolic dysfunction. [5, 6, 7, 8, 9]
Well documented for their anti-inflammatory effects, concentrated fish oils as a source of EPA and DHA have the potential to ameliorate adipose tissue inflammation in subjects with obesity and insulin resistance. It is believed that fish oil can also affect adipose tissue by the activation of PPAR leading to decreased lipolysis and improved lipid storage capacity in subcutaneous adipose tissue, as well as anti-inflammatory effects, including inhibition of NF-κB.
Studies indicate that there is an inverse relationship between long-chain omega-3 levels in erythrocytes and adiposity in humans. [10, 11] There are, of course, several logical reasons to explain such an observation. Firstly, being obese may simply incline individuals to include less fish or fish oil in their diet or, it may simply be reflective of a poor quality diet in general. In addition, long-chain omega-3 can suppress fat synthesis and increase metabolism in adipose tissue via multiple mechanisms involving altered expression of transcription factors (via SREBP-1 and PPARs, for example).  Having higher omega-3 levels could, therefore, reduce total adiposity as reflected by a lower BMI.
Fanning the flames of chronic illness
Whilst increasing omega-3 status and targeting inflammation-driven processes that underpin them may seem like an essential step to reducing the chronic illness burden of increased fat mass, excess body fat, and especially visceral fat, is highly correlated with systemic oxidative stress. Compared to non-obese individuals, obese individuals have higher levels of oxidatively modified macromolecules, such as malondialdehyde and oxidised low density lipoproteins, together with lower levels of antioxidants and antioxidant enzymes, which indicate excess oxidative stress with lowered antioxidant defence. [13,14] In addition, a vast number of studies link oxidative stress with the health complications of obesity, suggesting it is also a major contributing factor in the progression of metabolic and cardiovascular illness, with or without obesity. [15,16,17,18]
It has long been assumed, and more recently confirmed, that inflammation and oxidative stress go hand in hand, one often triggering or exacerbating the other. A recent review by Subrata Kumar Biswas in the Journal of Oxidative Medicine and cellular longevity goes so far as to say that much of the negative research around the benefits of antioxidants could be as a result of their inability to significantly target inflammatory pathways.  As such, and in light of heavier individuals being likely to require far higher doses of omega-3 than individuals of lower or normal weight to achieve ‘optimal’ levels, intervention must be approached with caution. As long-chain polyunsaturated fats, EPA and DHA are highly susceptible to peroxidation, and considering overweight individuals are likely to be nutritionally depleted, with a lower antioxidant status, their therapeutic use may result in pro-inflammatory, rather than anti-inflammatory effects.
As alluded to in Biswas’ review, a number of studies have suggested that lipid peroxidation, one physical manifestation of oxidative stress, could explain why omega-3 fats, in some cases, do not deliver the expected clinical benefits, even in conditions known to have an inflammatory basis. In a study conducted by Mazereeuw et al., they were able to show that high lipid peroxidation in depressed patients was linked to inadequate antioxidant supply to address free radical levels. They went on to suggest that omega-3 supplementation could therefore be harmful to depressed patients with high oxidative stress, if the latter is not also addressed. 
Interestingly, when oxidative stress is high, the one-carbon cycle, which is closely linked to fatty acid metabolism, naturally shifts away from neurotransmitter synthesis and DNA methylation to the transulfuration pathway – which is responsible for the synthesis of glutathione. As such, high oxidative stress may be responsible for rapid degradation of omega-3 fats and add to, not aid, inflammation.
Ensuring safe and successful nutritional intervention
It is clear that addressing both antioxidant status and providing the correct dose of omega-3 is imperative for successful outcomes, both to ensure optimal levels are achieved and to prevent too much omega-3 being given in a potentially volatile environment. The amount of omega-3 required to both increase and maintain a healthy omega-3 index in a high-risk individual is likely to be considerably higher than previously estimated, making individualised dosing, in fact, a necessity. The Igennus Opti-O-3 biomarker test takes client weight and baseline omega-3 status into account to determine the specific amount of omega-3 required to raise their omega-3 levels to optimal – between 8-10% – as determined by the work of Professor William Harris.  Identifying the correct dose as well as the required type of fat on an individual basis can help to reduce not only the burden of incorrect omega-3 doses but also of the wrong fats. DHA, for example, being the most unsaturated of the omega-3s, has been linked to worsening of inflammatory illness in multiple studies, likely as a consequence of high oxidative stress.
Co-supplementation with anti-oxidants alongside concentrated omega-3 supplements and choosing anti-oxidants that target inflammatory pathways, as well as combatting oxidative stress, is imperative in clients with high risk of compromised antioxidant status. Coenzyme Q10 as ubiquinol is, for example, not only a potent scavenger of free radicals, but also inhibits lipid and protein peroxidation, making it an ideal supplement to take alongside concentrated omega-3 products.  In addition, curcumin, best known for its anti-inflammatory and anti-cancer activities, also demonstrates considerable antioxidant actives by reducing malondialdehyde levels whilst raising the activity of a number of antioxidant enzymes including glutathione, glutathione peroxidase, catalase and superoxide dismutase, thereby further contributing to increased antioxidant capacity. 
In our increasingly complex and convoluted world it is clear that the need to address each client on a case-by-case basis and weigh up all factors before recommending a specific intervention, is a necessary clinical process. Testing for known biomarkers and dosing according to scientifically validated optimal levels, where possible, together with assessment of the environment and its impact on said intervention, and choosing suitable complementary nutrients to combat any potential negative impact, are key steps in managing the multifaceted basis of illness as it presents today, and creating successful clinical support plans.
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- Spencer M, Finlin BS, Unal R, Zhu B, Morris AJ, Shipp LR, Lee J, Walton RG, Adu A, Erfani R, et al: Omega-3 fatty acids reduce adipose tissue macrophages in human subjects with insulin resistance. Diabetes 2013, 62:1709-1717.
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