Newly established clinical biomarkers including the AA to EPA ratio highlight the extent to which inflammation underlies chronic illnesses. Dr Bailey presents compelling evidence for an EPA-based fatty acid approach to resolving inflammation that, when applied together with Igennus’ new Opti-O-3 blood spot fatty acid biomarker test, provides an effective nutrition management strategy for health practitioners treating a variety of conditions. Learn how this straightforward blood spot method can add value to your clinical approach by identifying your clients’ individual omega-3 requirements needed to manage biomarkers that correlate with long-term health and reduced disease risk.
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
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
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
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
9mg/kg/day for 50kg person or 5mg/kg/day for 90kg
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
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
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.
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
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
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
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
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
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
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
In addition to improving theomega-3 index, increasing omega-3 intake also has ad addional impact of improving the omega-6 to omega ratio
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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Our kit is
Using a linear model to predict
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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.