Clearly, in CVD trials - participants with a high Omega-3 Index at baseline [and presumably throughout the study] few, if any, CVD events are to be expected, whereas they are more likely in individuals with a low Omega-3 Index
A large intervention trial based on the Omega-3 Index with clinical endpoints remains [needs] to be performed
100,000 years ago
EPA DHA Total omega-3 Concentrated fish oil (rTG) 650 450 1100 Concentrated fish oil (EE)
Combining the AA to EPA ratio with the omega-3 index gives us a comprehensive overview of health status Although quite different metrics, there is a strong relationship between the serum EPA/AA ratio and the RBC omega-3 index (r ¼ 0.96, Harris, unpublished data). The baseline serum EPA/AA ratio reported in the JELIS study was 0.57 , which corresponds to an omega-3 index about 9%
Average omega-3 index is 5.1
Take with meals and before bed. Required for serotonin, dopamine and GABA = helps to calm and relax
How to ensure client success: reviewing the evidence
How to ensure client success:
reviewing the evidence.
Today’s talk objectives:
• To gain a deep understanding of why nutrition
research often fails to produce expected results
• To review the latest evidence on which nutrients
really work – with a focus on brain health
• Understand how failures in research methods help us
to be better clinicians
• Learn how to use this information to ensure success
with your clinical protocols
Why fish oils fail
(according to the research headlines)
Alarming headlines, but
DO FISH OILS REALLY FAIL?
“Do fish oils REALLY keep the brain
young? Study finds 'no evidence' that
omega-3 supplements slow mental
“Is your omega-3 fish oil
supplement any good - or a
load of old codswallop?”
“Omega-3 supplements do little to
protect you from heart diseases,
says new study”
“The benefits of omega-3
“Experts cast doubt
Inconsistencies arising from dietary intervention studies give mixed results and create confusing
messages (Von Schacky 2015; Harris 2015)
Poor heterogeneity in study designs, background diets, endpoint definitions, and baseline fish or
omega−3 fatty acid intakes cloud meta-analysis outcomes
Patients recruited regardless of their baseline levels and treated with fixed doses
Recent RCTs (virtually all of which have been conducted in European or North American cohorts
[low dietary fish intakes]) use relatively low doses (376–850 mg EPA & DHA) which at least partly
explains their failure
CVD secondary-prevention populations - include many individuals who are already taking multiple
heart medications such as statins, aspirin, and ACE inhibitors, which may obscure the effect of
omega-3 fatty acids
The inter-individual variability in response to a fixed dose of EPA + DHA has been found to be large,
i.e. to vary up to a factor of 13
Not all ‘fish oils’ are the same - addressing quality/concentration and purity
Study design to incorporate use of biomarkers?
Many factors influence the endogenous production of long-chain omega-3 (EPA &
o Genetics (delta-5, delta-6 polymorphisms)
o Diet and lifestyle factors (omega-6 intake, micronutrient status, smoking, etc)
Many factors influence how we utilise omega-3 in supplement form, i.e.
o Omega-3 baseline levels
o Body weight, age, gender, etc
Supplement digestibility/bioavailability [rTG, EE, phospholipids]
Understanding the dose-response effects of EPA and DHA and ‘condition related’
o EPA vs DHA – no longer viable to address them simply as ‘omega-3’
Tissue concentrations of these omega-3 fatty acids may be critical to achieving biological
Increasing omega-3 intake is not the same as increasing omega-3 levels!
Omega-3 dosing – ‘one size fits all?’
Effects of a single dose of EPA & DHA (3.4 g) taken with
breakfast on the Omega-3 index (n =20)
(Harris et al., 2013)
40 individuals with a baseline omega-3 index <5%
(black bar) and post treatment (white bar) after a 6-
week intervention with omega-3 EPA & DHA (0·5 g/d)
• The mean omega-3 index increased from 4·37% to
6·80% and inter-individual variability in response was
high (varied by a factor of up to 13 inter-individually)
(Kohler et al. 2010)
Strength/concentration of the active ingredient
within the total oil volume
Bioavailability of the omega-3 form used
Accurate ‘dosing’ – as [mg/kg/day] determined
according to the baseline omega-3 index
Adopting a ‘one size fits all’ approach is no longer viable for
maximising therapeutic success
What can we, ‘the practitioners’, do? Adopt a personalised ‘biomarker approach’ to treatment!
For an intervention to be successful you need to raise omega-3 levels and reduce the
inflammatory capacity of omega-6 AA
A combination of factors determine omega-3 intervention success:
TG EE rTG PL
The EPA/DHA dilemma
Although EPA and DHA are both long-chain polyunsaturated fatty acids (PUFAs), the
molecules are often reported to produce biochemical and physiological responses that are
qualitatively and quantitatively different from each other
The kinetics of EPA and DHA differ between different cell types
The marked differences between the effects of EPA and DHA indicate that it is an over-
simplification to generalise the effects of omega-3 PUFA on cell function
It is the EPA in excess of DHA that is the active component in fish oil [treating depression]
Verlengia et al., 2004; Martins 2009; Sublette et al., 2011; Russell & Burgin-Maunder 2012
EPA and DHA utilisation differences
High DHA intake reduces delta-6-desaturase activity
Studies often report no increase in DHA levels with pure EPA
supplementation – DHA saturation?
In some cases [depression/neurodevelopmental disorders] high
DHA supplementation has been shown to worsen health outcomes
12 week intervention with 1.8 g omega-3 (1.2g EPA + 0.6g
DHA) in young healthy males aged 18-25
During the washout period, EPA and DHA levels decreased
back to baseline levels, with EPA levels rapidly returned to
baseline levels within 2 weeks of stopping fish oil
supplementation, while serum DHA returned to baseline
levels only by the end of the washout period
Suggests high EPA requirements
Roke & Mutch 2014
The unique benefits of pure EPA
EPA (unlike DHA) reduces the pro-inflammatory activity of AA in a number of ways
EPA is an inhibitor of the enzyme delta-5-desaturase that produces AA
EPA directly displaces AA from cell membranes
EPA competes with AA for the enzyme PLA2 necessary to release AA from the membrane
EPA competes with COX and LOX enzymes to prevent the conversion of AA to its
As such, studies show that EPA plus DHA oils are less effective at reducing inflammation
than pure EPA oils
The power of rTG omega-3
Dyerberg et al., 2010 graph shows the % increase in serum EPA+DHA content following 2 weeks of EPA
and DHA supplementation Av. 3.3g per day.
rTG oil delivered biggest increase in serum lipid content in the lowest volume of oil and
lowest total dose of EPA+DHA (all others delivered 200mg EPA + DHA or more)
Importance of oil concentration
Higher concentrations increase cellular omega-3 levels more than the same
dose provided at a lower concentration
Brunton and Collins 2007
Importance of dose plus concentration
Higher dose high concentrations from rTG fish oil increase cellular omega-3
levels up to 5x more than krill oil and 3x more than standard fish oil
Laidlaw et al.,
dose of rTG, EE
fish oils with Krill
oil (PL) and
salmon oil (TG)
Subjects (n = 35) were randomly assigned to consume one of four products, in random order,
for a 28-day period, followed by a 4-week washout period
Subsequent testing of the remaining three products, followed by 4-week washout periods,
continued until each subject had consumed each of the products
Laidlaw et al., 2014
A randomised clinical trial to determine the efficacy of manufacturers’ recommended doses of
omega-3 fatty acids from different sources in facilitating cardiovascular disease risk reduction
Biomarkers for personalising omega-3 fatty acid dosing
Omega-6 to omega-3 ratio
an established marker of long-term health
(but fails to distinguish between the long- and
short-chain FA within each class)
AA to EPA ratio
a measure of ’silent’ or chronic inflammation
an early cardiovascular risk indicator
A personalised plan aims to achieve:
an omega-6 to omega-3 ratio of between 3 and 4
an AA to EPA ratio of between 1.5 and 3
an omega-3 index of more than 8%
Baseline 4 months ∆ change Outcome
Omega-3 index 3.50 5.98 +2.48 Undesirable to desirable
AA to EPA ratio 8.52 3.54 - 4.98 Suboptimal to acceptable
Case study – subject X (50kg female)
Improvement in both AA to EPA ratio and omega-3 index after 4 months
supplementation with EPA 30mg/kg EPA (equivalent of 1.5g daily)
Pharmepa® RESTORE & MAINTAIN™
The fastest, most effective, clinical omega-3
EPA, DHA and GLA
Minimum 3-6 months
Therapeutic role of Pharmepa®
RESTORE & MAINTAIN™
AA to EPA ratio
Symptoms of inflammatory illness
Optimum brain, cell, heart, immune
and CNS function
AA to EPA ratio
Long-term general and cellular health
Heart, brain and eye health
Reduce risk of chronic illness and help
protect against inflammatory disease
Part 2 : Brain-boosting bio-actives:
what really works?
Why brain health is HOT right now
• 1 in 4 suffer with a mental health condition
• 12 million adults see their GP for this – most cases stress-
related anxiety and depression
• 13.3 million working days lost each year due to stress-related
• Cognitive decline and dementia are on the rise
• 1 in 5 older adults suffer with depression and/or dementia
• 7% of over 65s have dementia
• 20% of over 80s have dementia
Issues affecting the brain and mind are widespread
With nearly all of UK adults affected by one of the four following need-states
determining how we can utilise nutrition to treat and prevent mental illness is of key
public health importance
Nutrition for brain and mental health –
Brain studies are extremely difficult to conduct
What's the optimal
length of time for
Which nutrients should
be used? Single, isolated
nutrients or blends….
What dose do we
What's the right
population for this study
What else might be affecting
the participants’ brains?
Omega-3 increases blood flow to the brain supplying oxygen and fuel delivery, are
essential for neurotransmitter production and function, memory, learning, cognition, and
brain and neurone cell structure
Benefits restricted to those with sub-optimal omega-3
intake – surprised?!
DHA is for memory and
learning if intake is low
EPA in excess of DHA for
cognitive performance, in
3 needed to
Many benefits of DHA
associated with increased
>1month intervention needed
for benefits to be seen
L-Theanine PLUS caffeine
• Potent fine-tuning of focus, concentration and memory
• Improved cognitive performance for demanding tasks
Amino Acids. 2000;19(3-4):635-42.
A taurine and caffeine-containing drink stimulates cognitive performance and well-being.
Seidl R1, Peyrl A, Nicham R, Hauser E.
The findings clearly indicate that the mixture of three key ingredients of Red Bull Energy
Drink used in the study (caffeine, taurine, glucuronolactone) have positive effects upon
human mental performance and mood.
Psychopharmacology (Berl). 2001 Nov;158(3):322-8.
An evaluation of a caffeinated taurine drink on mood, memory and information processing
in healthy volunteers without caffeine abstinence.
Warburton DM1, Bersellini E, Sweeney E.
In both studies, the caffeinated, taurine-containing beverage produced improved attention
and verbal reasoning, in comparison with a sugar-free and the sugar-containing drinks. The
improvement with the verum drink was manifested in terms of both the mean number
correct and the reaction times. Another important finding was the reduction in the variability
of attentional performance between participants.
• L-Theanine + taurine calm and focus the mind via GABA and
• Caffeine stimulates the brain, increasing energy, alertness and
information processing speed
• L-Theanine + caffeine enhance focus and reduce distractibility
• EPA and DHA are essential for mood-regulating
neurotransmitter production and function
• EPA reduces inflammation, which directly attacks and
degrades serotonin, leading to low mood and depression
• acts as a mood stabiliser
• low levels increase risk of anxiety and depression
• Studies show mixed results (in some case worsening) in
‘all studies without flaws demonstrated a statistically significant
improvement in depression with Vitamin D supplements…… the
effect size was comparable to that of anti-depressant medication.’
NB: Only effective in those who are deficient AND dose given must
result in a changed serum Vit D level
Recent study using NHANES data found significant
relationship between very low magnesium status and
Tarleton and Littenberg March 2015 http://www.ncbi.nlm.nih.gov/pubmed/25748766
glycinate/taurinate form (1-
300mg <4 times daily) shown
to quickly and effectively
relieve depression symptoms
BUT almost all studies of omega-3 use to boost
cognitive function have shown little or no
benefits – why?
• Study population
• Dose given
• EPA or DHA
• Cognitive tests chosen
• Duration of intervention time
• Is it already too late?
• B1,2,3 and 5
– support mitochondria of the brain and CNS
– aid detoxification pathways
– reduce inflammation
• B6, B12 and folate in their most active and bioavailable forms
– homocysteine recycling
– elevated levels = significant risk factor for age-related cognitive decline
MMSE scores showed a significant improvement in 43% patients of group A (26 subjects)
and 23% of group B (15 subjects), compared to baseline (𝑃 = .001). Also ADAS-Cog,
CIBIC, and ADFACS scores showed a significant improvement in group A versus group B.
IR was higher in group A. Our study suggests that ALA therapy could be effective in
slowing cognitive decline in patients with AD and IR.
– supports mitochondrial function
– slows ageing process via interaction with
Antioxidant combination formulas supply potent antioxidant
defence and recycling of body’s antioxidant pool to help reduce
free radical damage to neurones and protect brain structure and
Ginseng has been shown to provide mild
cognitive enhancement as well as improve
Was found to increase cognition and
improve symptoms of cognitive
decline after 4-6 weeks of use
Gingko Biloba studies have found
it provides a notable benefit to
cognition and symptoms of cognitive
Part 3 : translating this into
successful personalised nutrition
and clinical practice
There are still numerous gaping holes in
research which, for now, prevent firm
conclusions from nutrition research.
So - what can we learn from the negative
studies and what we can do in clinic to
ensure therapeutic success?
1: Choosing the right dose for EACH participant
It is increasingly apparent that the right dose for the right person is vital in
ensuring study success.
Before the study even begins we must know each individual participant’s baseline
level of the nutrient being investigated and, where possible, dose according to
pre-determined and validated dosing guidelines.
Translated into a practical clinical setting, testing is key to understand biochemical
individuality and whether or not your client actually needs, and will indeed benefit
from, a specific nutrient intervention. **
Using established dosing guidelines where available - such as that calculated using
the omega-3 index biomarker and body weight – can at least help us to achieve
health-protective levels of a nutrient in our clients, from which we can try to
establish the therapeutic dose.
2: What plasma or cellular levels need to be reached in order to have a
clinical effect in this specific area of health?
Whilst there is still no known ‘ideal’ plasma level of each and every nutrient for each and
every condition, the severity of deficiency tells us whether the nutrient in question is
likely to contribute to clinical results and how high we should commence the dose.
Remember - the lower the baseline levels (and the bigger/heavier they are), the more a
person will need to take in order to raise their plasma levels to that associated with
Those with the lowest baseline levels are likely to have the highest level of dysfunction.
Raising their levels closer to ‘ideal’ should help them to notice a tangible benefit to their
health. People with closer to adequate plasma levels may still benefit but the scale of
improvement is likely to be smaller and may therefore go unnoticed.
Using current levels and dosing between known therapeutic doses and upper tolerable
limits will help to get quicker positive results.
3: How does the body prioritise which clinical benefit it needs most?
If the client or study participant has more than one condition with high
requirements of this particular nutrient how do we determine how the body
will prioritise distribution?
If you have 3 major organ systems all requiring additional support and you give a
relatively modest dose of a nutrient which is known to contribute to all of these
systems, then perhaps most, or all, of that nutrient, gets shuttled to the organ
with the greatest need.
How do we dose correctly if more than one system is crying out for the
We need to look at the body as a whole when designing single nutrient studies for
single clinical benefits to determine if an endogenous competition might be the
reason for our negative outcome!
4: One nutrient alone does not always have the power to significantly
benefit one area of health
This is really key and is the reason humans have evolved to eat food, not
The brain is the most complex of all the organs and as yet we don’t know which
nutrients are ‘most’ important for cognitive function.
It is likely that looking at the overall benefits of a combination of nutrients is
much more useful than looking at each nutrient’s impact alone.
The positive research for specific diets in supporting healthy cognitive ageing,
such as the MIND diet, is much better established than most isolated nutrients.
….is a combination of the Mediterranean diet and the blood pressure-lowering DASH diet.
The MIND diet encourages consumption of ‘brain-healthy’ foods, including:
- green leafy vegetables, such as spinach and kale, other vegetables, such as red peppers, squash, carrots
and broccoli, nuts, berries (including blueberries and strawberries), beans, lentils and soybeans,
wholegrains, seafood, poultry, olive oil, wine (in moderation)
And avoidance of unhealthy foods including:
- red meats, butter and stick margarine, cheese, pastries and sweets, fried or fast food
• The MIND diet involves eating "brain-healthy" foods, with particular emphasis on eating berries, such
as blueberries, and green leafy vegetables, like spinach
• Unlike DASH and Mediterranean diets, MIND does not require eating lots of fruit, dairy or potatoes, or
eating more than one fish meal a week
• One study of the MIND diet found participants who stuck rigorously to the diet were 52% less likely to
be diagnosed with Alzheimer's disease
The MIND diet…..
5: Choose the right participants for this study and choose what
specific outcome suits them best?
If you want to be sure your client, or participant, will respond it is clear you
a) choose a nutrient that they actually need
b) use a population who require the targeted benefit.
There’s no point in targeting someone with depression knowing it has
inflammatory roots and choosing to give them glucosamine to treat non-
existent joint pain and then expecting their joint pain to improve!
In the AERDS2 study it is clear, for a number of reasons, that both omega-3 and the population
chosen were not ideal for the desired outcomes to be tested. The participants were not
malnourished, poorly educated or financially disadvantaged - all factors known to correlate with
fish consumption and increased risk of brain function decline.
6 and 7: When and for how long is optimal for this intervention?
Understanding what factor, and at which point in the life cycle, has the ability
to impact on long-term health outcomes is vital in determining the likelihood
of positive outcomes from clinical studies.
If the ‘damage’ has already been done, an intervention may only prevent
worsening of symptoms, rather than result in benefits and…
If the intervention is not given for the optimal length of time it may never
The order and length of interventions we choose to use in our day-to-day
clinics will determine if, and to what extent, a client will respond.
1. Which symptoms
and systems are of
most concern to you
AND your client?
5. So where
do I start?
4. Does this
Choosing the right intervention:
Questions you need to ask
Is the intervention you
choose right for the
Is the nutrient right at this
time in their treatment
What else might be
or not this nutrient
could be effective?
there be in the
body for this
What are their current
levels of this nutrient?
What other nutrients are needed
to make sure this nutrient can
work in the desired area?
• Choose an optimal starting dose
• Limit changes to other factors that could affect positive
outcomes or reduce the likelihood of noticing a benefit
• Make sure the client can be and is committed to compliance
• Don’t overwhelm the system with single nutrient
interventions; optimise the baseline diet and lifestyle and
target systems, not symptoms, initially
• Introduce new nutrients slowly, review regularly, and
routinely stop intake to make sure the nutrients chosen are
individually beneficial and contributing significantly at that
point in the protocol
• Plot it out!
Planning how the whole process of support might look,
what to give and when, relative to the specific organ system and
outcome of greatest concern, from the outset of treatment,
together with recognising the importance of compliance to
certain interventions beyond just a few months,
as well as not being afraid to revisit treatment options at
different times in a treatment plan
is essential to creating a successful support plan.
Part 4 : Advanced nutrition
support for the brain, tailored for
today’s busy lives
MindCare® - product range
Igennus MindCare® is the first comprehensive range of targeted brain nutrition
supplements based on four identified consumer need-states.
Transform how you feel™
MindCare® omega-3 EPA &
DHA capsules with vitamins
D & E
Precisely formulated to target and support brain
function (250mg DHA plus 410 mg EPA per
capsule) using the body-ready rTG form of
omega-3 that is nature-identical and easily
absorbed by the body
full B complex plus zinc,
selenium, vitamin C and
Target distinct areas of brain health with a
comprehensive blend of synergistic vitamins,
minerals and specialist actives at proven,
effective levels and in super-bioavailable forms
MindCare® is based on cutting edge nutrition science, and combines premium
triglyceride omega-3 fish oil containing 80% active doses of EPA and DHA with
scientifically proven nutrients for various aspects of brain health
MindCare® BALANCE is designed specifically to target the
physiological changes associated with stress and feeling
overwhelmed, to help you stay relaxed and keep on top of life
glycinate and L-Theanine
MindCare® FOCUS is designed to optimise focus and
attention, allowing you to stay alert and fulfil your potential
when you need it most
MindCare® LIFT supplies the nutrients needed to protect
neurotransmitter production and function, boosting serotonin
naturally, to help you stay happy and enjoy life
glycinate and 5-HTP
MindCare® PROTECT is uniquely formulated to support brain
function as we age and protect against oxidative stress-induced
damage, to help you stay sharp and get the most out of life
alpha lipoic acid and
• Highly researched and expertly formulated for maximum benefits
• Contains highly bioavailable omega-3 EPA and DHA
– nourishes, protects and repairs the brain and neurone structures
– enhances cellular communication and blood flow
– prevents oxidative & inflammatory damage
• Active, bioavailable and specialised
– mitochondrial function
– neurotransmitter production and
– antioxidant protection and detoxification
– reduce overstimulation of HPA-axis and
CNS in response to stress
– support natural biological functions
needed for optimal brain health
you to regain
control and stay
keep on top of
Fine tunes your
you can stay
alert to fulfil
needing a little
chemicals so you
can stay happy
and enjoy life.
Helps adults to
stay sharp by
mood as you age,
so you can get
the most out of