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

Introducing MindCare®

Having specialised in omega-3 lipid therapeutics for over a decade, we havetranslated our extensive expertise from our cutting edge science-based omega-3 EPA supplements and our understanding of brain development, cognition andmental health into a premium mass market wellbeing offering for adults seeking tomake the most of life. MindCare® supplements deliver the foundationalingredients for the brain and all-round health to transform how people feel.

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?

Omega-3s

Lipids and the brain 18 = Stearic18:2 = Linoleic20:3 = DGLA20:4 = AA22.5 = DPA

18.3 = α-LA20.5 = EPA22.5 = DPA22.6 = DHA

EFSA panel outcomes of DHA:

• The Panel notes that there is a well established role of DHA in brain function

• The Panel concludes that a cause and effect relationship has been established between the consumption of DHA and the maintenance of normal brain function

• The Panel considers that in order to bear the claim, foods should contain 250 mg of DHA in one or more servings

http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/3840.pdf

• Dominant polyunsaturated fatty acid in the brain• DHA vital for structure of the brain • Own unique structure ensures membranes are fluid and flexible

• Vital neuroprotection– neurotransmission, membrane channel and receptor function,

synaptic plasticity – memory and learning

DHA and the brain

• Structurally, EPA not a key player but numerous other roles make it vital for brain structure and function

– protects DHA via reducing phospholipase A2 activity– major anti-inflammatory eicosanoid precursor – directly competes with

and displaces AA to reduce inflammation– interacts with genes directly to stimulate neurone growth and

differentiation– reduces oxidative stress– enhances focus, attention and processing speed – rapid β-oxidation in preference to DHA providing fuel for mitochondrial

energy production

EPA and the brain

• EPA directly reduces stress perception and protects against HPA-axis dysregulation

• Reducing inflammation protects against degradation and reduced transportation of neurotransmitters at the synapse

Repeated exposure to stress = HPA-axis hyper responsiveness, anxiety, depression, inflammation, oxidative stress and increased cell ageing

Bosma-den boer 2012, Laugero et al., 2011Furuyashiki 2012 Keikolt-Glaser., 2010, Ros., 2009

EPA and the brain

• EPA turnover considerably higher than DHA (brain DHA turnover is very low 4-5mg/day)

• Requires constant replenishment at higher levels than DHA– protects against the high levels of

inflammation, oxidative stress and HPA-axis dysregulation, common to modern diet and lifestyles

• EPA in excess of DHA – necessary to elicit mood and anti-inflammatory benefits

EPA and the brain

Roke and Mutch 2014:Supplementation with 1200mg EPA + 600mg DHA in young healthy males ages 18-25 for 12 weeks followed by 6 weeks washout

BUT - does your fish oil deliver?

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)

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)

B vitamins

• Vital for energy metabolism, synthesis of neurotransmitters, antioxidant protection

• Ensures optimal delivery of fuel to the brain – enhances cognition, relaxation, sleep, mental focus and

reduces stress and oxidative stress

B vitamin complex

• Homocysteine recycling – by-product of the methylation cycle – necessary for the production of:– SAMe – metabolism of neurotransmitters serotonin, melatonin and dopamine– cysteine and glutathione – vital for antioxidant protection and detoxification processes– DNA – cell cycle, genetic replication, growth and development– carnitine, choline and CoQ10 – energy metabolism and mitochondrial function– myelin proteins – nerve transmission and CNS communication

• Homocysteine accumulation affects every function right down to the cellular level

B vitamin complex

Other vital vitamins

Vitamin C • further supports detoxification, provides antioxidant

protection against free radicals • reduces tiredness and fatigue• necessary for the proper functioning of the CNS and

psychological functioning

Vitamin E• sunflower seed source• antioxidant protection

Vital vitamins

Vital vitamins

Vitamin D

• expression of nootropics (‘smart’ drugs)

• neurone growth and development

• calcium homeostasis – neurone firing

• detoxification - helping to rid the brain of protein build-ups

Mind-modulating minerals

Zinc • essential to the production of neurotransmitters• enhances neurotransmission via interaction with receptors, transporters

and ion channels in the neurone and synapse

Selenium• up-regulates glutathione production• main component of antioxidant enzymes• supports proper adrenal function – commonly disrupted by high stress and

poor diet – leads to poor sleep, memory problems and fatigue

Magnesium

• Regulates the CNS via – neurotransmitter synthesis– neurone activity – synaptic plasticity

Immune function and the brain

• Stress, busy lifestyles, poor diet, ageing, poor sleep and low mood all negatively impact the immune system

• When we get sick, brain function and mood are dramatically reduced

• Vitamin C, E, D, zinc, selenium, omega-3 and B vitamins all work together to enhance, support and protect immune function

• Reduces likelihood of illness

• Prevents stress-induced immune weakening

Immune function and the brain

Stress and anxiety

Chronic stress

HPA axis over-stimulation

Excess cortisol Inflammation Oxidative stress, lipid peroxidation

Low serotonin, GABA and dopamine, anxiety, depression, tiredness, fatigue, immune suppression

Chronic stress

HPA axis over-stimulation

Excess cortisol Inflammation Oxidative stress, lipid peroxidation

Low serotonin, GABA and dopamine, anxiety, depression, tiredness, fatigue, immune suppression

Omega -3

Chronic stress

HPA axis over-stimulation

Excess cortisol Inflammation Oxidative stress, lipid peroxidation

Low serotonin, GABA and dopamine, anxiety, depression, tiredness, fatigue, immune suppression

Vitamins C and B

Selenium protects thyroid function, reducing impact of HPA-axis overstimulation

Vitamin B5 helps regulates adrenal function – reducing hypersensitivity to stress

Magnesium

• Neurotransmitter production • Vitamin B6 absorption• Required by 325 enzymes (many of which

act in the brain)• Neurone health, synaptic plasticity,

learning and memory [51,52]

• Low magnesium levels linked to anxiety, depression, irritability, insomnia, confusion….[50]

L-Theanine• Amino acid commonly lacking in modern diet• Present in tea!

SerotoninHappiness

Sleep

DopamineFocus Motivation Learning Anti-

anxiety

GABARelaxation

Ashwagandha

ValerianRhodiola

Reduction of stress and insomnia

Anti-anxiety benefits

Prevents high cortisol production

Protects against stress induced immunosuppression

Minor benefits to anxiety sleep and fatigue

Increased subjective wellbeing in stressed fatigued individuals

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

Zinc is necessary for neurotransmitter production and helps to ensure sustained, optimal neurone firing

Acetyl-L-Carnitine• Transports fat directly to the mitochondria of brain cells• Increases noradrenaline, dopamine and serotonin and their receptors

– increases memory and cognitive function

L-Theanine PLUS caffeine • Potent fine-tuning of focus, concentration and memory• Improved cognitive performance for demanding tasks

Taurine is an amino sulfonic acid that acts as a lipid/membrane stabiliser in the body and can aid various antioxidant defence systems.

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/

B Vitamins

• Vitamin B3 helps to reduce inflammation and increase dopamine synthesis [14]

• Vitamin B7 helps to stabilise blood sugars and reduce mood swings [30,31]

• B12 and folate – vital for homocysteine recycling (and therefore SAMe production) – levels linked to positive affect in healthy population (Edney et al., sept 2015 http://www.ncbi.nlm.nih.gov/pubmed/26346363)

• B6 (P5P) positively correlates with tryptophan levels and reduced kynurenine pathway metabolites

(Deac et al., April 2015 http://www.ncbi.nlm.nih.gov/pubmed/25833774)

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]

5-HTP

Is the direct precursor to serotonin and unlike tryptophan cannot be used for niacin or protein synthesis

It easily crosses the blood brain barrier

Currently, St John’s Wort is the much better researched source and contains approx. 25% active 5-HTP

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

Alpha-lipoic acid– reverses age-related oxidative damage – metal chelator – prevents build-up in blood

and brain– stabilises mitochondrial membranes– improves age-related cognitive decline [70, 71, 72]

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?

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™

72

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

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

MindCare® micronutrient capsules contain:full B complex plus zinc, selenium, vitamin C and targeted ACTIVES 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

With: Magnesium 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

With: Acetyl-L-Carnitine, L-Theanine, taurine and caffeine

MindCare® LIFT supplies the nutrients needed to protect neurotransmitter production and function, boosting serotonin naturally, to help you stay happy and enjoy life

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.

For those needing a little pick-me-up. Protects & enhances your feel-good chemicals so you can stay happy and enjoy life.

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.

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