how to ensure client success: reviewing the evidence
TRANSCRIPT
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
Part 1: Why fish oils fail
(according to the research headlines)
Alarming headlines, butDO FISH OILS REALLY FAIL?
“Do fish oils REALLY keep the brain young? Study finds 'no evidence' that
omega-3 supplements slow mental decline”
“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 seem fishy”
“Experts cast doubt on omega-3”
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 & DHA), i.e.
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 levelso Body weight, age, gender, etc
Supplement digestibility/bioavailability [rTG, EE, phospholipids]
Understanding the dose-response effects of EPA and DHA and ‘condition related’ requirements 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 effects
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
Time (weeks)
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 phospholipids
EPA competes with COX and LOX enzymes to prevent the conversion of AA to its eicosanoids
As such, studies show that EPA plus DHA oils are less effective at reducing inflammation than pure EPA oils
BUT - does your fish oil deliver?
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., 2014 Comparison of manufacturer- recommended dose of rTG, EE concentrated 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 inflammationOmega-3 index an early cardiovascular risk indicator
A personalised plan aims to achieve:an omega-6 to omega-3 ratio of between 3 and 4an AA to EPA ratio of between 1.5 and 3 an omega-3 index of more than 8%
Baseline 4 months ∆ change OutcomeOmega-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 intervention
‘RESTORE’ pure EPA
‘MAINTAIN’EPA, DHA and GLAMinimum 3-6 months
Therapeutic role of Pharmepa®RESTORE & MAINTAIN™
AA to EPA ratio Inflammatory regulation Symptoms of inflammatory illness Optimum brain, cell, heart, immune
and CNS function Optimum wellbeing
Omega-3 index 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
illness• 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
The Problem
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
• Depression will affect 1 in 4 people in their life
• 7% of over 65s have dementia. Expected to increase by 40% in next 12 years
• 3.2m (13%) adults work 48hrs/week; 16% in South East England
• 1/4 of adults have taken sick leave due to stress; 10% of adults have occasional panic attacks
Stress Mental performance
MoodCognitive decline
Nutrition for brain and mental health –the evidence
Brain studies are extremely difficult to conduct
Why??
What's the optimal length of time for this intervention
Which nutrients should be used? Single, isolated nutrients or blends….
What dose do we give?
What's the right population for this study and intervention?
What else might be affecting the participants’ brains?
Focus, attention and cognitive performance
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 particular attention
Total omega-3 needed to be >400mg
‘DHA only’ often resulted in detrimental effects to cognition
Many benefits of DHA associated with increased blood flow
>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.RESULTS:
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 dopamine activation
• Caffeine stimulates the brain, increasing energy, alertness and information processing speed
• L-Theanine + caffeine enhance focus and reduce distractibility
Mood balance
Omega-3
• 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
Depression Sublette 2011 Meta-analysis
Grosso et al., 2014
http://www.ncbi.nlm.nih.gov/pubmed/24805797
Vitamin D
• acts as a mood stabiliser
• low levels increase risk of anxiety and depression
• Studies show mixed results (in some case worsening) in managing depression
‘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 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011048/
Recent study using NHANES data found significant relationship between very low magnesium status and depression
Tarleton and Littenberg March 2015 http://www.ncbi.nlm.nih.gov/pubmed/25748766
Magnesium
Supplementation with glycinate/taurinate form (1-300mg <4 times daily) shown to quickly and effectively relieve depression symptoms [50]
Cognitive decline
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?
B vitamins
• 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 ( = .001). Also ADAS-Cog, 𝑃CIBIC, 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.
Resveratrol
– supports mitochondrial function– slows ageing process via interaction with
sirtuin enzymes
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
function
Ginseng has been shown to provide mild cognitive enhancement as well as improve subjective wellbeing
Bacopa MonnieriWas 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 decline
What else?
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 health benefits.
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 nutrient?
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 nutrients.
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
http://www.nhs.uk/news/2015/08August/Pages/new-brain-diet-slows-mental-decline.aspx
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 need to 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 reach significance.
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.
Creating a plan of action: Where do I start?
1. Which symptoms and systems are of
most concern to you AND your client?
2. What strategies can you
implement?
5. So where do I start?
4. Does this change the
benefit gained or
perceived?
Choosing the right intervention:
Questions you need to ask
Is the intervention you choose right for the client?
Is the nutrient right at this time in their treatment plan?
What else might be affecting whether or not this nutrient could be effective?
What other demands might there be in the body for this nutrient?
What are their current levels of this nutrient?
What other nutrients are needed to make sure this nutrient can work in the desired area?
?
Start here:
Planning for success:
factors to consider
• 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!
Tools
Planning how the whole process of support might look, including:
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.
Stress Mental performance Mood Cognitive
decline
Transform how you feel™
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A simple, expertly formulated, 1-a-day dual capsule systemUltra concentrated MindCare® omega-3 EPA & DHA capsules with vitamins D & EPrecisely formulated to target and support brain
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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
With: Magnesium glycinate and L-Theanine
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With: Acetyl-L-Carnitine, L-Theanine, taurine and caffeine
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With: Magnesium 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
With: Acetyl-L-Cysteine, alpha lipoic acid and resveratrol
• 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
MindCare®Ingredients summary
• Active, bioavailable and specialised micronutrient blends– mitochondrial function– neurotransmitter production and
function– antioxidant protection and detoxification– reduce overstimulation of HPA-axis and
CNS in response to stress– support natural biological functions
needed for optimal brain health
MindCare® Mechanisms summary
MindCare® Benefits summary
Calms the mind, helping you to regain control and stay relaxed and keep on top of life.
Fine tunes your attention & supercharges your mental processing so you can stay alert to fulfil your full potential.
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Helps adults to stay sharp by protecting the brain structure, memory and mood as you age, so you can get the most out of life.
Sophie TullyBSc MSc DipPT Nutrition Education Manager
http://igennus.com/professionals/