Complete Synapse

SKU: 1544
Supportive Function: The ultimate support for brain, nerve cell and nerve synapse function to optimize cellular communication, utilizing heavily researched brain nutrients like bacopa, glucoraphanin, ashwagandha, and many others.

When is Brain Support helpful? Brain Function; Healthy Aging; Nerve cell / Glial cell function; Nerve Synapse function; Nerve cell to nerve cell communication; Nerve cell to other receptor cell communication; Cognitive function; Normal HPA axis function; Communication within brain areas: Hypothalamus, Amygdala, etc., Stress, Antioxidant status, General well-being, Mental health.
Clinical Applications Research: Bacopa (bacopamonniera) is one of the herbs in a category known as adaptogens. A systematic review of six randomized, controlled human clinical trials was conducted on cognitive domains and the herb “Bacopa (bacopamonniera)”. Scientists recognized that traditional knowledge suggests bacopa is well known for supporting cognitive function in the brain, and they concluded that bacopa definitely supports cognition. They noted that research on bacopa and cognitive support is in its infancy “with research still yet to investigate the effects of Bacopa across all human cognitive abilities” (Pase MP, et al. Effects of Bacopamonnieri: a systematic review of randomized, controlled human clinical trials.J Altern Complement Med. 2012 Jul;18(7):647-52).

In a randomized, placebo-controlled, double-blind trial involving 98 healthy older persons (over 55 years in age) in Australia, audioverbal and visual tests were used to assess performance over 12 weeks. Researchers believed that bacopa offers significant support and that their results concur “with previous findings and traditional use (Morgan A, &Stevens J. Bacopamonnieri … Results of a randomized, placebo-controlled, double-blind trial.J Altern Complement Med. 2010 Jul;16(7):753-9). Another randomized, placebo-controlled, double-blind trial evaluated 54 healthy elderly people 65 or older from Portland, OR. Similar results were obtained, and researchers concluded that bacopa had a good safety and tolerability profile (Calabrese C et al. Effects of a standardized Bacopamonnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial.J Altern Complement Med. 2008 Jul;14(6):707- 13).

Trans Pterostilbene: Multiple studies have demonstrated the antioxidant activity of pterostilbene, a natural dietary compound (related to resveratrol) and the primary antioxidant component of blueberries. The pterostilbene found in plants like blueberries acts as part of its defense system.Trans-pterostilbene is the pure form, and it has increased bioavailability in comparison to other stilbene compounds, which may enhance its dietary benefit and possibly contribute to a valuable clinical effect (McCormack D, McFadden D.A review of pterostilbene antioxidant activity ….Oxid Med Cell Longev. 2013;2013:575482). The unique structure of pterostilbene makes it oil-soluble and more bioavailable than resveratrol, another type of stilbene, resulting in greater metabolic stability which lasts longer in the blood (Ferrer P. et al. Association between pterostilbene and quercetin….Neoplasia. 2005 Jan;7(1):37-47). Nutakul W et al.(2011) also referred to the “superior bioavailability of pterostilbene to resveratrol” (Nutakul W et al.Inhibitory effects of resveratrol and pterostilbene… a side-by-side comparison.J Agric Food Chem. 2011 Oct 26;59(20):10964-70). McCormack & McFadden noted that the clinical effects can be particularly supportive of neuronal and vascular health. Other researchers of stilbenes (Kasiotis KM. et al. 2013) describe the “significant biological activities of medicinal interest”, calling the antioxidant properties “well established and subjects of numerous research endeavors.” The mini-review focused on research findings, the mechanisms underlying their effects, and respective signaling pathways. This blueberry-derived compound exerts supportive effects on neurons by crossing the blood brain barrier and maintaining central nervous system signals (Andres-Lacueva, C. et al. Anthocyanins in aged blueberry-fed rats …,” Nutritional Neuroscience, vol. 8, no. 2, pp. 111–120, 2005). No wonder we are told to eat blueberries for brain function!

Blueberry (fruit) have other active ingredients besides pterostilbene. Blueberry phytochemicals were first found to cross the blood brain barrier by Andres-Lacueva C. et al. (2005) and localize in various brain regions. Correlational analyses revealed a relationship between test performance in BBS rats and the total number of blueberry compounds. Their findings suggest “that these compounds may deliver their antioxidant and signaling modifying capabilities centrally” (Andres-Lacueva C. et al. Anthocyanins in aged blueberry-fed rats are found …NutrNeurosci. 2005 Apr;8(2):111-20).

Glucoraphanin (as broccoli seed extract) (sulforaphane) comes from cruciferous vegetables (broccoli, kale, cabbage, cauliflower etc.), and results in sulforaphane production. Both glucoraphanin and sulforaphane are well known for their antioxidant, high-powered phytochemical activity. Glucoraphanin “may target epigenetic alterations” and optimize our health status by providing these vegetable extracts that have such a wide reputation for health benefits (Antioxid Redox Signal. 2014 Nov 3. Dietary Sulforaphane…: The Role of Epigenetic Regulation and HDAC Inhibition.Tortorella SM. et al). The powerful support that glucoraphanin has on epithelial cells is evidenced by the effect it has on supporting the integrity of the blood brain barrier (Giacoppo S. et al. The … effects of bioactive (RS)-glucoraphanin on the permeability of the mice bloodbrain barrier...Eur Rev Med Pharmacol Sci. 2014;18(2):194-204). Researchers determined that a 10% broccoli diet was supportive in some areas for brain neurons, but that broccoli by-products like sulforaphane, which are more concentrated, “would need to be provided in supplement form” in order to support a normal non-inflammatory environment (Townsend BE. et al. Dietary broccoli in aged mice…. Nutr Res. 2014 Nov;34(11):990-9).

Ashwagandha (root) (Withaniasomnifera) contains many extracts and bioactive components, including arabinogalactan, withanone and withanolide A. Ashwaganda is considered to be an ayurvedicadaptogen, a substance that supports physiological functions disturbed by chronic stress.The ability it has to act as a free radical scavenger helps cells during toxic insult; ashwaganda significantly raised antioxidant enzymes like catalase and superoxide dismutase in brain tissue (Kumar P. Glio… effects of Ashwagandha leaf extract …Biomed Res Int. 2014;2014:182029).

One scientific review described ashwaganda as “the best known and most scientifically investigated” of Indian ayurvedic herbs (Ven Murthy MR. et al. Scientific basis for the use of Indian ayurvedic medicinal plants…: ashwagandha.Cent NervSyst Agents Med Chem. 2010 Sep 1;10(3):238-46). The mechanisms are wide and diverse, but some include opioid receptor pathways, oxidative pathways,and neuronalpathways (Nosálová G. et al. Antitussive activity of Withaniasomnifera and opioid receptors. AdvExp Med Biol. 2015;838:19-25).

N. Shah et al. (2015) found these extracts to possess activities very supportive of glial and neuronal cells, especially in the midst of oxidative insult; they not only found low doses to be effective, the combinations of different ashwaganda extracts were “highly potent” and caused them to endorse the therapeutic merit of the combinational approach”. These researchers also described the potential of ashwaganda for neuronal support and declared that it “may serve as a supplement for brain health” (Combinations of Ashwagandha Leaf Extracts Protect Brain-Derived Cells against Oxidative Stress and Induce Differentiation.PLoS One. 2015 Mar 19;10(3):e0120554. Shah al). Another study also suggests that properties of ashwaganda may provide explanation for the uses of it in traditional medicine for cognitive support (Kurapati KR. et al. Human neuronal cells and … effects of ashwagandha (Withaniasomnifera) and its constituent Withanolide A.PLoS One. 2014 Nov 21;9(11):e112818).

DHEA - 3-acetyl-7-oxo-dehydroepiandrosterone (or 7-Keto DHEA) is a metabolite of DHEA, however it possesses unique qualities because of its oxygenated 7-position. One of the qualities is to support the thyroid, especially T-3, which is the active thyroid hormone (Kalman, DS. et al. A randomized, double-blind, placebo-controlled study of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy overweight adults. Current Therapeutic Research 61(7), July 2000).
DHEA is synthesized in the brain, has long had a traditional reputation for brain support, and decreases with age. DHEA metabolizes to other steroids and can carry side effects, however 3-acetyl-7-oxo has been described as “possibly more effective than (DHEA) without the prohormonal effects” (Goncharov NP, Katsia GV.Neurosteroiddehydroepiandrosterone and brain function. FiziolCheloveka. 2013 Nov-Dec;39(6):120- 8;Worrel ME et al.Alcohol. 2011 Jun;45(4):349-54). Unlike DHEA, this derivative of DHEA is not converted to steroid hormones and does not increase the level of steroid hormones in the blood (Web MD 2015).It has been found to be safe and well tolerated (no adverse effects in any of the studies), rapidly absorbed and excreted (half-life of 2.17 hours) and there is no accumulation with repeated dosing (Davidson, M. et al. "Safety and Pharmacokinetic Study with Escalating Doses of 3-acetyl-7-oxo-dehydroepiandrosterone in Healthy Male Volunteers". Clin. Invest. Med. 2000; 23 (5): 300–310).

DHA (as spirulina): A systematic literature search was conductedof clinical trials and observational studies that examined the relationship between long chain omega 3 fatty acids on cognitive support in healthy adults. Scientists reported that DHA (docosahexaenoic acid) alone (or in combination with EPA) contributed to the supportive effect on the brain of long chain omega 3’s (Yurko-Mauro K. et al. Docosahexaenoic Acid and adult memory: a systematic review and meta-analysis.PLoS One. 2015 Mar 18;10(3):e0120391). Microglial cells can have both direct and indirect effects on synaptic structures and functions. Glial cells are non-neuronalcells that maintain homeostasis, form myelin, and provide support for neurons in the brain and peripheral nervous system. The integrity of dendritic spines, the postsynaptic component of excitatory synapses, dictates synaptic efficacy. It is very important to support glial, microglial, and dendritic spines to ensure proper support of brain and nerve communication support, and DHA is reported to do just that (Chang PK. Et al. Docosahexaenoic acid (DHA): a modulator of microglia activity and dendritic spine morphology.J Neuroinflammation.; 2015 Feb 22.12(1):244).

One factor evidently important for neuronal health and function is the optimal supply of nutrients necessary for maintaining normal functioning of the brain; mechanistic studies, epidemiologic analyses, and randomized controlled intervention trials provide insight to the positive effects of docosahexaenoic acid (DHA) in helping neurons to “cope with aging” (Mohajeri MH. Et al. Inadequate supply of vitamins and DHA in the elderly: implications for brain aging and Alzheimer-type dementia.Nutrition. 2015 Feb;31(2):261-75).

Alpha Keto-glutaric Acid, or α ketoglutarate, is a key intermediate in the Kreb’s Cycle, a biochemical reaction that constantly transpires within our cells to make energy (ATP). Two thirds of the brain's energy is utilized to help nerve cells "fire'' or send signals. The remaining third is used for cell-health maintenance. One of alpha ketoglutarate’s physiological purposes is to be a carrier of nitrogen to the urea cycle in the liver, where ammonia is detoxified, and indeed alpha ketoglutarate has demonstrated the ability to detoxify ammonia accumulation in the brain (Ott, P. et al. Cerebral metabolic disturbances in the brain during acute liver failure: from hyperammonemia to energy failure and proteolysis.". Neurochemistry international 2005 47 (1-2): 13–8; Hares, P. et al. Effect of ornithine alpha ketoglutarate (OAKG) on the response of brain metabolism to hypoxia in the dog. Stroke; a journal of cerebral circulation. 1978;9 (3): 222–4). Another interesting physiological purpose of alphaketoglutarate is that it is required for the hydroxylation of proline to hydroxyproline in the production of collagen.

Vitamin B-6, Vitamin B-12 (as methylcobalamin) and Folate (as L-5 methyltetrahydrofolate): B vitamin support has been extensively studied and it is well-known that B vitamins, specifically three B vitamins in particular, help maintain methylation pathways and provide support for the brain. In a groundbreaking two year randomized controlled trial of 156 subjects, Douaud G. et al. published a report on May 20, 2013 in the journal Proc Natl AcadSci U S A. that named three major B vitamins for supporting brain activity and cognitive processes. Those B vitamins were: Vitamin B-6, vitamin B- 12, and folic acid. Although the study did not distinguish between the active forms of the vitamins, the active form of folic acid (5 MTH Folate) is powerful and beneficial to people who are impeded in their methylation capabilities (about 50% of the population), methyl B-12 is the active form of vitamin B-12, and Pyridoxal-5-Phosphate is the active form of vitamin B-6.

The study determined that daily amounts of folic acid (800 mcg) along with vitamin B-12 (500 mcg) and vitamin B-6 (20 mg) provided excellent support for brain function, brain volume, and normal cognitive processes. Their recommendation, in approaching effective brain support, was to utilize a supplement plan containing these amounts of those three B vitamins.

Berberine augments the antioxidant defense system and helps maintain nerve health; researchers believed that their study provided evidence that it has potential as a neuro-supportive agent (Abdel Moneim AE et al. The …effect of berberine in mercury-induced neurotoxicity in rats.MetabBrain Dis. 2015 Jan 21). Additional studies bolster the notion that berberine is good support for brain/nerve function, healthy cell communication, motor balance, neurotransmitter balance, and nerve integrity (Kim M. et al. Berberine ...Int J Mol Med. 2014 Apr;33(4):870-8; Wang CM. et al. Comparison of Two Old Phytochemicals versus Two Newly Researched Plant-Derived Compounds: Potential for Brain...; Evid Based Complement Alternat Med. 2014;2014:682717).

L-Theanine is the amino acid in green tea responsible for some of its effects. L-theanine and green tea were discovered (in a double blinded placebo controlled trial of 91 people) to support healthy brain function, especially in the temporal, frontal, parietal, and occipital areas of the brain (Park SK, et al. A combination of green tea extract and l-theanine… a double-blind placebo-controlled study.J Med Food. 2011 Apr;14(4):334-43) Kim TI et al. (2009) suggest that some of the effects of L-theanine are due to the influence on ERK/p38 kinase and NF-kappaB pathways (Kim TI et al. L-Theanine, an amino acid in green tea … reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-kappaB pathways.Free RadicBiol Med. 2009 Dec 1;47(11):1601-10).

Phosphatidyl Choline (as sunflower Lecithin) is an emulsifier, high in phosphatidyl choline, that is beneficial for increasing the absorption and bioavailability of many nutrients. Lecithin is also known for fostering a normal non-inflammatory state, and has been researched for its favorable effects in supporting health. Lecithin has lowered C-reactive protein in some studies (CRP is an inflammatory marker).

Black Pepper (Piper nigrum) is a spice referred to by many as a “functional food”; the bioactive components present in it “are of considerable significance owing to their potential” (Butt MS. et al. Black pepper and health: a comprehensive treatise.Crit Rev Food SciNutr. 2013;53(9):875-86.) Butt MS. Et al. (2013) wrote a “comprehensive treatise” (by their own description), of health associations to piper nigrum, and point out that the widespread recognition of diet-health linkages bolsters the dietary importance of spices, calling piper nigrum “an important healthy food” owing, in part, to its antioxidant, gastro- and cognitive supportive qualities. Piperine is the main active ingredient, rich in the phytochemistry of black pepper that also includes volatile oil, oleoresins, and alkaloids. Piper nigrum attenuated oxidative stress in the rat hippocampus, helping to achieve brain health homeostasis (Hritcu L. et al. Methanolic extract of Piper nigrum… decreasing brain oxidative stress in… rat model ….Cell MolNeurobiol.2014 Apr;34(3):437-49). Piper nigrum also supports neurotransmitter production and postsynaptic currents (ProgNeuropsychopharmacolBiol Psychiatry. 2011 Jun 1;35(4):1144-7. Involvement of serotonergic system in the …effect of piperine.Mao QQ et al.; Food ChemToxicol. 2008 Sep;46(9):3106-10. Piperine, the potential functional food.Wattanathorn J. et al.; Biol Pharm Bull. 2010;33(4):598-603. …Effect of piperine on primarily cultured hippocampal neurons.Fu M. et al.)

Thyme (leaf) and Oregano (leaf) are also spices, and they are rich in active substances like carvacrol; carvacrol is a “brain-active” molecule that supports brain neurochemistry, the central nervous system, neuronal activity and neurotransmitters, and “if regularly ingested in low concentrations, it might determine feelings of well-being” (Zotti M. et al. Carvacrol: from ancient flavoring to neuromodulatory agent.Molecules. 2013 May 24;18(6):6161-72).

Cinnamon, a widely-used food spice and flavoring material, was investigated for its supportive effect on levels of nerve messengers such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in the central nervous system (CNS). Scientists reported that their results highlight a novel property of cinnamon to help maintain homeostasis of nerve factors in the CNS (Jana A. et al. Up-regulation of neurotrophic factors by cinnamon … implications.J NeuroimmunePharmacol. 2013 Jun;8(3):739-55). Other evidence also contributes to the theory that cinnamon is a highly beneficial spice and supports brain, cognitive function, and the nervous system (Anderson RA et al. Cinnamon counteracts the negative effects of a high fat/high fructose diet...PLoS One. 2013 Dec 13;8(12):e83243).

For optimal brain function, we must nourish the varied areas of the brain and spinal cord that contribute to the smooth operation of all brain components. Nerve cells release neurotransmitters (NTs), and those neurotransmitters communicate with receptors via nerve synapses. Nerve synapses are junctions between the release and the receptor (the receptor can be another nerve cell) that allow the neurotransmitter to reach its goal and effect change. The synapse in essence permits a nerve cell (neuron) to pass an electrical or chemical signal to the other cell (receptor). Neurotransmitters like dopamine, serotonin, acetylcholine, epinephrine and norepinephrine have the ability to emit those signals to their receptors. There are also neurotransmitters released in the gut which communicate with the brain via neuronal pathways to the brain, including the vagal pathway, emphasizing the importance of a healthy gut as well.
Contraindications: Minor GI side-effects have been observed at relatively high doses of 300 mg bacopa every day for 12 weeks; Complete Synapse contains < 55 mg per serving. Bacopa might increase levels of thyroid hormone or slow heart rate (Web MD). Not recommended for pregnancy or lactation.
Ingredients: Folate (as L-5 methyltetrahydrofolate) 275 mcg, Vitamin B-12 (as methylcobalamin) 200 mcg. Proprietary blend 254.8 mg* of: DHA (as spirulina) Phosphatidyl Choline (as sunflower lecithin), Bacopa (monniera) Extract (root), Ashwagandha (root), Glucoraphanin (as broccoli seed extract), DHEA, Alpha Ketoglutaric Acid, Trans Pterostilbene, Berberine, L-Theanine, Thyme (leaf), Oregano (leaf), Blueberry (fruit), Cinnamon (bark), Trimethylglycine, Pyridoxal 5 Phosphate, Black Pepper (piper nigrum).
Vegetarian: No
Suggested Dosage: 1 tablet daily or as directed
Pack: 60 Tablets
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