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Nina Bailey 
BSc (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 
Prostaglandins 
Thromboxanes 
Leukotrienes 
Resolvins 
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 balance 
The 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
R² = 0.649 
14 
12 
10 
8 
6 
4 
2 
0 
1 2 3 4 5 6 7 8 
Omega-3 index 
Omega-6 to Omega-3 ratio 
R² = 0.6493 
14 
12 
10 
8 
6 
4 
2 
0 
0 5 10 15 20 
Omega-3 index 
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 index 
an early cardiovascular risk indicator 
Omega-6 to omega-3 ratio 
an established marker of long-term health and chronic illness 
AA to EPA ratio 
a 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 4 
An AA to EPA ratio of between 1.5 and 3
R² = 0.649 
14 
12 
10 
8 
6 
4 
2 
0 
1 2 3 4 5 6 7 8 
Omega-3 index 
Omega-6 to Omega-3 ratio 
R² = 0.6493 
14 
12 
10 
8 
6 
4 
2 
0 
0 5 10 15 20 
Omega-3 index 
AA to EPA ratio 
In house data n=25 
A higher omega-3 index correlates with a lower AA to EPA ratio
Omega-3 index 
an early cardiovascular risk indicator 
Omega-6 to omega-3 ratio 
an established marker of long-term health and chronic illness 
AA to EPA ratio 
a 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 4 
An 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.com 
www.igennus.com 
drninabailey.co.uk 
0044 1223 421434
Opti-O-3 blood spot biomarkers in clinical nutrition, with Dr Nina Bailey

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Opti-O-3 blood spot biomarkers in clinical nutrition, with Dr Nina Bailey

  • 1. Nina Bailey BSc (hons) MSc PhD ANutr
  • 2. 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
  • 3. 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)
  • 4. 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 Prostaglandins Thromboxanes Leukotrienes Resolvins As omega-3 intake increases, there is a corresponding increase in metabolites
  • 5.
  • 6. 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
  • 7. 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
  • 8. 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
  • 9. 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)
  • 10. Risk of sudden cardiac death and omega-3 blood levels Source: Albert et al., 2002
  • 11. Harris & Von Schacky, 2004
  • 13. 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 )
  • 14. 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)
  • 15. 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
  • 16. 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
  • 17. Shifting the balance The 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
  • 18. R² = 0.649 14 12 10 8 6 4 2 0 1 2 3 4 5 6 7 8 Omega-3 index Omega-6 to Omega-3 ratio R² = 0.6493 14 12 10 8 6 4 2 0 0 5 10 15 20 Omega-3 index AA to EPA ratio In house data n=25 A higher omega-3 index correlates with a lower AA to EPA ratio
  • 19.
  • 20. 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)
  • 21. 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
  • 22. Omega-3 index an early cardiovascular risk indicator Omega-6 to omega-3 ratio an established marker of long-term health and chronic illness AA to EPA ratio a 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 4 An AA to EPA ratio of between 1.5 and 3
  • 23.
  • 24.
  • 25.
  • 26. R² = 0.649 14 12 10 8 6 4 2 0 1 2 3 4 5 6 7 8 Omega-3 index Omega-6 to Omega-3 ratio R² = 0.6493 14 12 10 8 6 4 2 0 0 5 10 15 20 Omega-3 index AA to EPA ratio In house data n=25 A higher omega-3 index correlates with a lower AA to EPA ratio
  • 27.
  • 28. Omega-3 index an early cardiovascular risk indicator Omega-6 to omega-3 ratio an established marker of long-term health and chronic illness AA to EPA ratio a 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 4 An AA to EPA ratio of between 1.5 and 3
  • 29. 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
  • 30. 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

Editor's Notes

  1. We have recently launched a blood spot fatty acid biomarker test to help practioners identify clients individual omega-3 requiresmnts Vv Some of the key issues facing practitioners is understand where fatty acid deficiency can play role in a clients symptoms, when supplementing with omega-3 fatty acids can be of benefit and predominantly, how much omega-3 is needed to elicit an improvement in symptoms There can be huge individual variation in response to treatment with omega-3 and there is increasing evidence to support a more tailored approach to dosing based on an individual's absolute omeaga-3 requirements rather than the ‘one size fits all approach. There may be situations when clients are using fatty acids as part of a treatment protocol but not experiencing improvements and as manufactures of pure EPA supplements it is important to us that
  2. 450 mg/ day works out at a dose of 9mg/kg/day for a 50kg person or 5mg/kg/day for 90kg person This doesn’t take into account the potential higher omega-3 requirements that occur in some health conditions We also need to consider the UK population’s expanding wastelines. Indeed 1993 - 13% of men 16% of women were obese 2011 - 24% for men and 26% for women Oositity is Low-grade systemic inflammation is highly prevalent and a known risk factor linked with Heart disease High blood pressure Asthma and breathing problems Diabetes Some types of cancer Neurodegenerative diseases and so on Compared to normal weight individuals, obese individuals have lower omega-3 concentrations, augmented inflammatory activity and endothelial dysfunction Elevated insulin suppresses desaturation enzymes
  3. 9mg/kg/day for 50kg person or 5mg/kg/day for 90kg
  4. Omega-3s and especially EPA is particularly important by directly influencing the resolution step of the inflammatory response And that failure to resolve inflammation increases susceptibility to the development of chronic, low-grade, inflammation-based diseases
  5. When omega-3 intake is increased delta-5 desaturase converts ETA to EPA and reduces the conversion of DGLA to AA The omega-6 family can give rise to both inflammatory and anti inflammatory end products, but the pathway taken (DGLA or AA) depends on how much omega-3 there is in the diet Further, EPA inhibits the enzyme delta-5 desaturase that would otherwise produce AA from DGLA
  6. So we can start to see how knowing a patient or clients omega-3 levels can influence how they are treated or how they will portnetially respond to a treatment.
  7. The 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
  8. Physicians health study (Albert et al., 2002) Prospective, nested case-control analysis among apparently healthy men who were followed for up to 17 years in the Physicians' Health Study The fatty-acid status of 94 men in whom sudden death occurred as the first manifestation of cardiovascular disease and for 184 controls matched with them for age and smoking status After adjustments, there was a 90% reduced risk of sudden death among men with levels of EPA and DHA (total omega-3) in the highest quartile as compared with the lowest quartile
  9. Increasing the omega-3 index is now well recoginsed to lower the risk of cardiovascular diease and a number of studies have shown that incorporation of omega-3 into RBC membranes increases in a dose-dependent manner
  10. However if we look at a more recent dose response study we can see huge variability between individuals A randomised, placebo-controlled, double-blind, parallel-group study (n=115) One of 5 doses (0, 300, 600, 900, 1800 mg) of EPA+DHA was given daily as placebo or fish oil supplements for 5 months Variability was influenced by baseline omega-3 index, with body weight the greatest influencer
  11. Generally EPA levels will return to base line levels within a few weeks of stopping supplementation whereas the washout period for DHA is much longer supporting the theory that EPA turnover and requirements are higher than that of DHA
  12. 50 kg person requires about 360 mg to get to 6, 860mg to get to 8 and 1.36g to get to 10 In comparison 70 kg about 500 mg to get to 6, 1.2mg to get to 8 and 1.9g to get to 10
  13. If we account for differences in body weight between individuals we could improve recommendations based in individual requirements, beacause body weight explains much of variability in omega-3 index response to omega-3 supplementation
  14. In addition to improving theomega-3 index, increasing omega-3 intake also has ad addional impact of improving the omega-6 to omega ratio
  15. The omega-6 family can give rise to both inflammatory and anti inflammatory end products, but the pathway taken (DGLA or AA) depends on how much omega-3 there is in the diet When omega-3 intake is increased delta-5 desaturase converts ETA to EPA and reduces the conversion of DGLA to AA Further, EPA inhibits the enzyme delta-5 desaturase that would otherwise produce AA from DGLA
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  20. Using a linear model to predict
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  23. A key question as a practitioner is how much omega-3 is needed to see noticeable improvements in symptoms? From intervention studies we know that in some cases, individuals with the lowest baseline levels of omega-3 see the strongest improvements. Omega-3 requirements can be effected by numerous factors such as individual requirements, age, sex, diet and base line levels. These variables may even explain why some intervention studies do always report statistically significant findings.