Nina BaileyBSc (hons) MSc PhD ANutr

Health consequences associated with low intake of the long-chain, marine omega-3 fatty acids have become a central issue in nutritional lipid research

Low-grade systemic inflammation is highly prevalent within the UK population and is and a known risk factor for numerous health conditions

Current recommendations for omega-3 intake are set at 450mg/day

The evidence that omega-3 can reduce disease risk (i.e. CVD) is sufficiently strong that both the American Heart Association and European Cardiology Society recommend intake of ≥1g

Additional intake of long-chain omega-3 fatty acid beyond current recommendation appears to be needed to raise omega-3 levels to predetermined levels defined as ‘health protective’

The importance of biomarkers: The omega-3 index could serve as a diagnostic and/or predictive biomarker of poor health/disease risk

AA to EPA ratio (correlates with symptom severity in numerous health conditions)

Omega-3 fatty acids have broad health-promoting effects, with diverse actions on genes, metabolism and multiple regulatory systems

Although omega-3 fatty acids have direct actions, they are also precursors to bioactive metabolites

ProstaglandinsThromboxanesLeukotrienesResolvins

As omega-3 intake increases, there is a corresponding increase in metabolites

The increase in the anti-inflammatory metabolites derived from EPA lowers the more pro-inflammatory metabolites derived from omega-6 AA

This is believed to, at least partially, explain the health benefits of omega-3 (fish/fish oil) consumption

Anti-inflammatory actions of omega-3 - well defined in vitro and animal experiments - demonstrate benefits of marine omega-3 fatty acids

Trials of marine omega-3 fish oil in patients are generally inconsistent

These conflicting results are likely due to differences in study design, sample size, sample studied, background diet, omega-3 supplement choice, dose, study length, baseline levels of omega-3, etc.

Often the most prominent outcomes are observed in those individuals with the lowest omega-3 levels and predominantly with the lowest levels of EPA

In spite of the importance of the omega-3 fatty acids, relatively few studies have monitored the correlation of supplement intake and subsequent enrichment of these fatty acids in RBC membranes and plasma

Measurement of EPA and DHA can be used to assess for suboptimal intake of omega-3 fatty acids

Biomarkers for personalising omega-3 fatty acid dosing The omega-3 index Omega-6 to omega-3 ratio AA to EPA ratio

The omega-3 index

The omega-3 index was originally developed as an informative risk factor for developing cardiovascular disease and is defined as the content of EPA and DHA in the cell membrane of RBCs, expressed as a weight percentage of total fatty acids and reflects tissue fatty acid composition (Harris & Von Schackey 2004)

Data from epidemiological and dietary intervention studies suggest a desirable target value for the omega-3 index of more than 8%, with less than 4% recognised as an undesirable level

A low omega-3 index is also associated with numerous health conditions including neurodevelopmental and mental health disorders, with increasing interest in its use as a biomarker of mental health (Milte et al., 2009)

Risk of sudden cardiac death and omega-3 blood levels

Source: Albert et al., 2002

Harris & Von Schacky, 2004

Flock et al., 2013

The incorporation of omega-3 into RBC membranes increases in a dose-dependent manner

Individuals with the lowest omega-3 index have been shown to respond more favourably than individuals with higher omega-3 levels

Individuals with a higher baseline omega-3 index have shown a lower omega-3 index response to treatment incorporating additional omega-3 at a slower rate than those with lower baseline levels

(Cao et al., 2006; Keenan et al., 2012; Flock et al., 2013 )

Additional intake of long-chain omega-3 fatty acid beyond current recommendation appears to be needed to achieve an omega-3 index considered to be health protective (8-10%)

Higher (initial) doses may be required to effect rapid change in individuals with lower initial omega-3 index values

An ‘average healthy adult’ with a low omega-3 index (i.e. 4.3%) would require at least 1 g/day of long-chain omega-3 for 5 months to achieve an omega-3 index of 8% (Flock et al., 2013)

Accounting for individual differences in body weight could potentially improve precision for omega-3 recommendations

Body weight explains a high level of variability in omega-3 index response to omega-3 supplementation

Individuals with lower (versus higher) body weight tended to have a greater response to set dose of omega-3

This suggests that omega-3 recommendations to achieve a target omega-3 index may be most appropriately made on the basis of body weight, similar to current dietary protein requirements

Western dietary and lifestyle factors, particularly those that create an inflammatory environment, contribute significantly to inflammatory-related disorders

Diets that are high in omega-6 increase ‘risk’, whilst diets that are rich in long-chain omega-3 may reduce ‘risk’

Specifically, a high AA to EPA ratio and low EPA [rather than DHA] appears to be associated with many inflammatory conditions

Modifying the diet can reduce systemic inflammation by manipulating the AA to EPA ratio

Shifting the balanceThe omega-6 to omega-3 ratio is well documented as a marker of health status; however, the ratio of AA to EPA is a more accurate indicator of inflammatory status

AA and EPA contents of cell membranes can be altered through consumption of omega-3 EPA (marine products/marine oils)

Changing the fatty acid composition of cell membranes affects

• changes in membrane structure

• products involved in immune function and the inflammatory cascade

• cell signalling

• gene expression and cell cycle control

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AA to EPA ratio

In house data n=25

A higher omega-3 index correlates with a lower AA to EPA ratio

The omega-6 to omega-3 ratio of the RBC membrane is significantly higher in patients compared to healthy comparisons

The fatty acid content of RBC membranes could serve as a diagnostic and/or predictive biomarker

Increasing research is focusing on lipid changes with relation to the duration and progression of conditions

(Rizzo et al., 2010)

Using the model developed by Flock and colleagues (2013), it is possible to estimate the dose (mg/kg/day) required to raise the omega-3 index to a desirable level (8-10%) knowing an individual’s baseline omega-3 level

The Opti-0-3 is the only omega-3 biomarker test that offers a bespoke dosing guide to optimise omega-3 fatty acid biomarkers for optimal health

Recommendations are to retest after 6-months

Omega-3 indexan early cardiovascular risk indicator

Omega-6 to omega-3 ratioan established marker of long-term health and chronic illness

AA to EPA ratioa measure of ’silent’ or chronic inflammation

A personalised plan aims to achieve:An omega-3 index of more than 8% (10%) An omega-6 to omega-3 ratio of between 3 and 4An AA to EPA ratio of between 1.5 and 3

R² = 0.649

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1 2 3 4 5 6 7 8

Om

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-3 in

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Omega-6 to Omega-3 ratio

R² = 0.6493

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AA to EPA ratio

In house data n=25

A higher omega-3 index correlates with a lower AA to EPA ratio

Omega-3 indexan early cardiovascular risk indicator

Omega-6 to omega-3 ratioan established marker of long-term health and chronic illness

AA to EPA ratioa measure of ’silent’ or chronic inflammation

A personalised plan aims to achieve:An omega-3 index of more than 8% (target 10%)An omega-6 to omega-3 ratio of between 3 and 4An AA to EPA ratio of between 1.5 and 3

Price? Kit RRP £120 Practitioner trade rate £65 + VAT Clients can purchase direct using affiliated

practitioner code (25% discount client/25% commission practitioner)

Turnaround time?7-10 working days

Dosing with omega-3 – how much do I need?

Establishing omega-3 levels identifies those individuals with higher omega-3 requirements

Knowing baseline levels of omega-3 enables a bespoke dosing that aims to achieve biomarker status associated with positive health outcomes

A long-term minimum maintenance dose of 500mg/day is advisable

Recommendations should be set to retest after 6 months to monitor outcomes

ninab@igennus.comwww.igennus.comdrninabailey.co.uk0044 1223 421434