Nutritional co-therapeuticsNeurobalanceTM

NeurobalanceTM

Zinc, magnesium & vitamin B6

1. Synthesis of the neurotransmitter

2. Storage of the neurotransmitter (in storage granules or vesicles in the axon terminal)

3. Release of the neurotransmitter into the synaptic cleft occurs as a result of calcium influx into the axon terminal during an action potential

4. The neurotransmitter then binds to and activates a receptor in the postsynaptic membrane

5. The neurotransmitter is either destroyed enzymatically, or taken back into the terminal from which it came, where it can be reused, or degraded and removed

Neurotransmission is the process by which signalling molecules (neurotransmitters) are released by a neuron (the presynaptic neuron), and bind to and activate the receptors of another neuron (the postsynaptic neuron); it can be defined by the following steps:

L-tryptophan

5-hydroxy tryptophan

Serotonin

Melatonin

Phenylalanine

Tyrosine

Dopa

Dopamine

Noradrenaline

Adrenaline

Acetyl-CoA Choline Glutamine

Glutamate

GABA

Acetylcholine

L-tryptophan

5-hydroxy tryptophan

Mg, Zn, B6

Serotonin

Melatonin

Phenylalanine

Tyrosine

Dopa

Dopamine

Mg, Zn

Mg, Zn

Zn, B6

Noradrenaline

Adrenaline

Zn, B6

Acetyl-CoA Choline Glutamine

Glutamate

GABA

Zn, B6

Acetylcholine

Neurotransmitter receptors and transporter proteins

Neurotransmitters are required to bind to receptors to exert its function

The physiological effect of the neurotransmitter is dependent not only on the activity of the receptor, but also ‘transporters’, membrane-spanning proteins that pump neurotransmitters out of the synapse back into the presynaptic cell, and into vesicles for later storage and release

The transporter protein, by recycling, regulates its concentration in the synapse, and thus its effects on the receiving neurone

Zn, Mg and vitamin B6 for neurotransmission

Zn, Mg and vitamin B6 play key roles in neurotransmitter synthesis

Zn and Mg play a role as neuromodulators by affecting the function of neurotransmitter receptors and transporter proteins

NeurobalanceTM

Magnesium (Mg), zinc (Zn) & vitamin B6 are key nutrients required for both neurotransmitter synthesis and function (via receptor and transporter proteins)

Deficiency in one or more of these nutrients can significantly impair normal neurotransmitter production and function

Vitamin B6 is required for transport or accumulation of Mg in cells and tissue

Mg is required for the proper functioning of alkaline phosphatase, the enzyme that facilitates the absorption of vitamin B6

Zinc is needed to convert the inactive form of vitamin B6, pyridoxine, to the active form pyridoxal phosphate

Neurodevelopmental disorders

Evidence suggests a breakdown in several neurotransmitter pathways in neurodevelopmental disorders, particularly dopamine, serotonin and GABA

Mg deficiency common in neurodevelopmental disorders Mg levels correlate highly with distractibility and excitability Mg levels associated with hyperactivity and sleep disturbances

Poor conversion of B6 to the active form pyridoxal-5-phosphate

B6 and Mg deficiency may result in accumulation of the tryptophan metabolite kynurenine, which is itself known to be associated with disturbances in neurotransmission (Ames et al., 2002)

Author Intervention Duration n = Assessment Findings

Mousain-Bosc et al, 2006

magnesium-vitamin B6 (Mg-B6) regimen (6 mg/kg/d Mg, 0.6 mg/kg/d vit-B6)

8-weeks 40 trial36 control(age 6-14)

DSM-IV Significant reduction in hyperactivity and aggressiveness. Improvements in attention.

Mousain-Bosc et al, 2004

Mg(2+)/vitamin B6 intake (100 mg/day)

12-weeks 579 boys231 girls(age 5-12)

SNAP-IV and SDQ

Overall improvements in attentional, behavioural and emotional problems.

Starobrat-Hermelin et al, 1997

Mg (200mg/day) or placebo

6-months 50 trial25 control(age 7-12)

DSM-IV Connors Rating Scale

Significant reductions in hyperactivity and improvedfreedom from distractibility.

Serum zinc levels have been found to be significantly lower in ADHD children compared to controls

Consumption of certain artificial food colour additives has also been shown to lead to zinc deficiency

Ingestion of 50mg tartrazine by 22 hyperactive males:

serum zinc levels decreased

urine levels increased

behavioural and emotional symptoms deteriorated

Ward et al. 1990 The Influence of the Chemical Additive Tartrazine on the Zinc Status of Hyperactive Children—a Double-blind Placebo-controlled Study Journal of Nutritional and Environmental Medicine. 1:51-57 

Author Intervention Duration n = Assessment Findings

Arnold et al, 2011

13-40mg zinc glycinate

Phase 1Zinc or placebo for 8 weeksPhase 2Zinc or placebo with d-amphetamine for 2 weeksPhase 3Zinc or placebo with d-amphetamine (adjusted)for 3 weeks

52(age 6-14)

DSM-IV No superiority of zinc when compared with placebo; when zinc was administered twice daily, the optimal weight-adjusted dose for amphetamine [could be] decreased by 37% compared with placebo.

Huss et al, 2010

4 capsules ‘ESPRICO’containing Zinc 5mg

12-weeks 579 boys231 girls(age 5-12)

SNAP-IV and SDQ

Overall improvements in attentional, behavioural and emotional problems.

Akhondzadeh et al, 2004

methylphenidate 1 mg/kg/day + zinc sulphate( 55 mg/day) methylphenidate 1 mg/kg/day + placebo(sucrose 55 mg)

6-weeks 26 boys 18 girls(age 5-11)

DSM-IV Improvements in both groups, but improvements were significantly greater in the zinc group.

Bilici et al, 2004

150mg zinc sulphate

12-weeks 328 boys72 girls(age=9.61±1.7)

DSM-IV Overall improvements in hyperactivity, impulsivity and socialization scores but not in attention.

Neurodegenerative disease

Nerve damage can occur as a consequence of dysregulated inflammation or as a result of scarring caused by protein aggregation (such as Lewy bodies, alpha-Synuclein and beta-amyloid)

Zinc has critical functions in the brain. Lack of zinc can cause neuronal death

Patients with Alzheimer's are often found to be zinc deficient when compared with age-matched controls (Brewer et al., 2012)

Mg deficiency has also been shown in patients with mild to moderate AD (Barbaqallo et al., 2011)

Women’s health

Reduced levels of several essential nutrients, including Mg, zinc and vitamin B6, are common in:

- women using oral contraceptives - women using hormone replacement therapy (HRT) - postmenopausal women

Given the role of Mg, zinc and vitamin B6 in regulating symptoms associated with premenstrual syndrome (PMT) and menopausal symptoms (including the risk of osteoporosis), restoring optimal levels via supplementation may be advisable

NeurobalanceTM key features and benefitsZinc methionine offers superior bioavailability, antioxidant and immune-enhancing properties compared to other forms of zinc.

cell replicationneurotransmitter synthesis & functionimmune functionessential fatty acid metabolism

Magnesium citrate is more soluble and bioavailable than magnesium oxide found in many cheaper supplements .Magnesium is required for the proper functioning of alkaline phosphatase, the enzyme that facilitates the absorption of vitamin B6.

energy productionnerve and muscle functionadrenal function hormone functionneurotransmitter synthesis & functionessential fatty acid metabolismcalcium metabolism vitamin B6 absorption

Pyridoxal-5-phosphate delivers the ‘body-ready’ form of vitamin B6. Vitamin B6 is required for transport or accumulation of magnesium in cells and tissue.

protein metabolism essential fatty acid metabolism energy production magnesium absorption

NeurobalanceTM

IngredientsMagnesium citrate; bulking agent: calcium carbonate; emulsifier: microcrystalline cellulose; zinc methionine; vitamin B6 (pyridoxal-5-phosphate); thickener: hydroxypropyl methylcellulose; anti-caking agents: stearic acid, silicon dioxide, magnesium stearate.

Nutritional information Serving size: 2 tablets Amount per tablet % RDA

Zinc methionine 14 mg 140 %

Magnesium citrateof which magnesium

367mg60 mg 16 %

Vitamin B6 (pyridoxal-5-phosphate) 10 mg 714%

NeurobalanceTM

Free from: Dairy Gluten Lactose Soya

Yeast Artificial colourings & flavourings Not tested on animals Non-GMO

Directions for useChildren aged 4-8 years should take 2 tablets daily. Children aged 9-15 years should take 4 tablets daily. Adults and children aged 16+ should take 6 tablets daily. For optimal results take with food and split into 2 doses per day. Do not exceed the daily dose unless advised by a healthcare practitioner.

Warnings and contraindicationsPregnant or lactating women should consult their doctor before taking any food supplement. This product should not be used as a substitute for a balanced diet. Keep out of the reach of children and away from sunlight. There are no known drug or nutrient interactions associated with Neurobalance™.

• Igennus is the only independent manufacturer of specialist Fatty Acid in the UK. Based in Cambridge the medical innovation hub for the UK:

- Seven Seas Merck Pharma Germany- Minami Atrium Pharma Canada- Biocare Elder Pharma India- Eskimo 3 Bringwell Pharma Sweden- Equizen Vifor Pharma Swiss

NeurobalanceTM

NeurobalanceTM is a blend of magnesium, zinc and vitamin B6, formulated to aid in normal neurotransmitter production and function. This scientifically formulated supplement offers synergistic benefits to optimise the functioning of the nervous system. Utilising a slow-release delivery system and the most bioavailable forms of each ingredient, NeurobalanceTM ensures optimal blood plasma nutrient levels are maintained throughout the day.

Highly bioavailable nutrients Synergistic relationship between Mg and B6 Easy-to-swallow tablets Split-dosing for optimal bioavailability Sustained-release tablets for enhanced absorption & optimal tissue distribution Offers benefits for brain function and mood

balance

Supports neurotransmitter metabolism Supports neurological function Supports hormone balance Supports immune function Supports DNA and protein synthesis Aids in the production of sleep modulators Supports a healthy mood Anti-anxiety benefits

ninab@igennus.comwww.igennus.comdrninabailey.co.uk

01223 42143407527384229

Magnesium absorption

Typical magnesium absorption:40% of magnesium intake absorbed in the small intestine5% absorbed in the large intestine55% leaves the body as waste

Forms of magnesium that dissolve well in liquid are more completely absorbed in the gut than less soluble forms

Mg citrate is considered to be highly bioavailable whereas certain forms of magnesium supplements, such as magnesium oxide, may have an absorbable magnesium potency as low as 4% (Lindberg et al., 1990)

Mg citrate

Mg gluconate

Mg lactate

Mg carbonate

Mg oxalate

Mg hydroxide

Mg oxide

Decreasing solubility