NeuBrain Revive Formulation

NeuBrain Revive promotes anti-inflammatory and detoxification support using multiple compounds that work synergistically to leverage the body’s innate ability to self-heal, including:

NeuBrain Revive

Alpha Lipoic Acid

  • Alpha lipoic acid has powerful antioxidant and anti-inflammatory properties. A molecule with powerful functions in the brain, alpha lipoic acid is active in the mitochondria, which are the components of cells involved in energy production and can be thought of as tiny organs within cells where energy is created from fuels such as oxygen. Alpha lipoic acid plays a number of roles in supporting the mitochondria, including acting as an antioxidant and influencing gene expression.  

    One of the strongest antioxidants in the brain, alpha lipoic acid has the ability to directly reduce “free radicals,” or unstable, reactive molecules that can be created by stresses on the body. It has a broader ranging effect than antioxidants such as vitamin C as it can act in both the cell fluid (cytosol) as well as the cell membrane. These antioxidant effects have been shown to protect cells against a wide variety of insults, including from heavy metals such as cadmium, side effects of chemotherapy, and head injuries. Consequently, alpha lipoic acid has been found to protect from inflammation in a number of illnesses, including Alzheimer’s, Parkinson’s, cancer, and even multiple sclerosis.  

    However, its effects are much more wide reaching than as an antioxidant—alpha lipoic acid can directly influence gene expression. Gene expression refers to the degree to to which a gene within in the DNA is turned into the protein it encodes. This protein can then act throughout the cell and beyond. The most well-known gene that alpha lipoic acid can “upregulate” is glutathione, which is another very powerful antioxidant. Other lesser known genes it has been shown to upregulate is PCNA (proliferating cell nuclear antigen) which is essential for DNA repair, and AMPK (adenosine monophosphatase protein kinase), which can sense when cellular energy is low and activate the mitochondrial response.

References

  • 1. Inflamm Res. 2017 Jul 4. doi: 10.1007/s00011-017-1079-6. [Epub ahead of print]. Biochemical and clinical relevance of alpha lipoic acid: antioxidant and anti-inflammatory activity, molecular pathways and therapeutic potential. Tibullo D1, Li Volti G1, Giallongo C1, Grasso S1, Tomassoni D2, Anfuso CD1, Lupo G1, Amenta F3, Avola R4, Bramanti V1,5.

    2. Diabetol Metab Syndr. 2014; 6: 80. Published online 2014 Jul 28. doi:  10.1186/1758-5996-6-80. PMCID: PMC4124142 Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases. Marilia Brito Gomes Corresponding author and Carlos Antonio Negrato

    3. Environ Toxicol Pharmacol. 2017 Apr;51:30-37. doi: 10.1016/j.etap.2017.02.022. Epub 2017 Feb 27.
    Regeneration of glutathione by α-lipoic acid via Nrf2/ARE signaling pathway alleviates cadmium-induced HepG2 cell toxicity. Zhang J1, Zhou X1, Wu W1, Wang J1, Xie H1, Wu Z2.

    4. Mol Med Rep. 2016 Nov;14(5):4360-4366. doi: 10.3892/mmr.2016.5754. Epub 2016 Sep 20. A-lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions. Li DW1, Wang YD2, Zhou SY3, Sun WP1.
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N-acetyl cysteine

  • N-acetyl cysteine raises levels of glutathione, one of the most powerful antioxidants in the body. It assists detoxification in the brain, and can help reduce irritability and addiction cravings.

    Focus on Mechanisms

    N-acetyl cysteine is a powerful antioxidant and anti-inflammatory agent of the body, which has both direct effects as well as raising levels of glutathione, arguably the most powerful antioxidant in the body. This enables it to perform multiple actions, including clear the body of toxins such as lead and defend from  infections.

    Effects of Brain

    Through its antioxidant functions, it has been found to lower inflammation in the brain. By lowering inflammation, some studies suggest it could support cognition, particularly if the brain is under stress.

    Effects on Addictions

    N-acetyl cysteine appears to support the brain in overcoming addictions. It has been studied in a variety of addictive states, and provides support in overcoming cigarette smoking and even stronger forms of addiction. Though naturally occuring in the body, it’s powerful enough that it’s still commonly used today in hospitals in certain situations of drug overdoses.

     

References

  • 1. Kasperczyk S1, Dobrakowski M, Kasperczyk A, Ostałowska A, Birkner E.Clin Toxicol (Phila). 2013 Jul;51(6):480-6. doi: 10.3109/15563650.2013.802797. Epub 2013 Jun 4.  The administration of N-acetylcysteine reduces oxidative stress and regulates glutathione metabolism in the blood cells of workers exposed to lead.

    1. 2. Knackstedt LA1, LaRowe S, Mardikian P, Malcolm R, Upadhyaya H, Hedden S, Markou A, Kalivas PW.Biol Psychiatry. 2009 May 15;65(10):841-5. doi: 10.1016/j.biopsych.2008.10.040. Epub 2008 Dec 21.  The role of cystine-glutamate exchange in nicotine dependence in rats and humans.

     

    1. 3. Zheng W1, Zhang QE2, Cai DB3, Yang XH1, Qiu Y1, Ungvari GS4, Ng CH5, Berk M6,7, Ning YP1, Xiang YT8.Acta Psychiatr Scand. 2018 Feb 18. doi: 10.1111/acps.12862. [Epub ahead of print] N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials.

     

    1. 4. Sadiq Naveed,1 Afshan Amray, 2 Ahmed Waqas, corresponding author 3 Amna M Chaudhary, 4 and Muhammad W Azeem 5 Cureus. 2017 Nov; 9(11): e1888.  Published online 2017 Nov 29. doi: 10.7759/cureus.1888 Use of N-Acetylcysteine in Psychiatric Conditions among Children and Adolescents: A Scoping Review. Monitoring Editor: Alexander Muacevic and John R Adler.

     

    1. 5. Bhatti J1, Nascimento B1, Akhtar U2, Rhind SG3, Tien H1, Nathens A1, da Luz LT1.  Front Neurol. 2018 Jan 15;8:744. doi: 10.3389/fneur.2017.00744. eCollection 2017.Systematic Review of Human and Animal Studies Examining the Efficacy and Safety of N-Acetylcysteine (NAC) and N-Acetylcysteine Amide (NACA) in Traumatic Brain Injury: Impact on Neurofunctional Outcome and Biomarkers of Oxidative Stress and Inflammation.

     

    1. 6. Duailibi MS1, Cordeiro Q2, Brietzke E2, Ribeiro M2,3, LaRowe S4, Berk M5,6, Trevizol AP3.  Am J Addict. 2017 Oct;26(7):660-666. doi: 10.1111/ajad.12620. Epub 2017 Sep .N-acetylcysteine in the treatment of craving in substance use disorders: Systematic review and meta-analysis.

     

    1. 7. David R.SkvarcacOlivia M.DeancdgLinda K.ByrneaLauraGraydStephenLanedeMatthewLewisahBrisa S.FernandescfMichaelBerkcdgAndrewMarriottbcd.  The effect of N-acetylcysteine (NAC) on human cognition – A systematic review.

     

    1. 8. Eduardo P. Amaral,1,2 Elisabete L. Conceição,3,4 Diego L. Costa,1 Michael S. Rocha,3 Jamocyr M. Marinho,5,6 Marcelo Cordeiro-Santos,7,8 Maria Regina D’Império-Lima,2 Theolis Barbosa,3,4 Alan Sher,1 and Bruno B. Andrade corresponding author 1,3,9,10.  BMC Microbiol. 2016; 16: 251.Published online 2016 Oct 28. doi: N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions.
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Methylcobalamin

The main form of vitamin B12 in the body, methylcobalamin plays multiple roles in brain cells, including detoxification and DNA synthesis. It is best known for its roles in energy metabolism and it also supports cognition.

 

Lowering Inflammation and Effects

Methylcobalamin lowers inflammation in cells. New studies suggest this will indirectly support healthy cognition, by removing the inflammation linked with different illnesses that affect memory.  The later effects of lowering inflammation can include lowering pain. In combination with folate, it’s also believed to positively affect mood.

 

DNA Synthesis and Ability to Absorb Light  

Methylcobalamin also plays an important role in the synthesis of new DNA and how a gene is expressed, or genetic expression. Recently, methylcobalamin has also been discovered to be a “photoreceptor,” which means it can absorb light.  Interestingly, this implies that light absorption activates methylcobalamin and influences gene expression in cells.

 

References

1. Kennedy et al. Nutrients. 2016 Feb; 8(2): 68. B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review

2. Moore et al. Proc Nutr Soc. 2018 Jan 10:1-12. doi: 10.1017/S0029665117004177. [Epub ahead of print]
Diet, nutrition and the ageing brain: current evidence and new directions. 

3. Werder et al. Neuropsychiatr Dis Treat. 2010; 6: 159–195. Cobalamin deficiency, hyperhomocysteinemia, and dementia.

4. Cheng et al. Cobalamin’s (Vitamin B12) Surprising Function as a Photoreceptor ,Trends Biochem Sci. 2016 Aug; 41(8): 647–650.

5. Cheng et al. Mol Microbiol. 2014 Feb; 91(4): 649–664. Vitamin B12 regulates photosystem gene expression via the CrtJ antirepressor AerR in Rhodobacter capsulatus

6. Chiu et al., Singapore Med J. 2011 Dec;52(12):868-73. The efficacy and safety of intramuscular injections of methylcobalamin in patients with chronic nonspecific low back pain: a randomised controlled trial.

7. Neural Plasticity Volume 2013 (2013), Article ID 424651, 6 pages

Quercetin

  • Quercetin is a “bioflavonoid,” a naturally occurring antioxidant found throughout many substances in nature. These compounds, as part of a larger family of compounds known as “polyphenols,” have been studied to have an exceptionally broad array of positive of effects for the brain and body, including lowering inflammation, protecting from cancer, supporting vascular health, lowering pain, and more. Quercetin functions at multiple locations in the cell, from the DNA to the outer membranes.

    One reason that quercetin has such a broad range of effects is that it can work at multiple cell levels. First, quercetin has the ability interact and incorporate itself into the outer layer of the cell, the cell membrane. At the opposite end of the spectrum, with regards to preventing cancer, it appears quercetin has the ability to directly bond with DNA.

    Quercetin has been shown to protect neurons from various types of stressors. As a result, it is hypothesized to protect from neurodegenerative illnesses such as Alzheimer’s. One study in animals actually showed that cognitive decline from severe inflammation can be reversed with flavonoids such as quercetin.  Quercetin is also being studied for treatment of depression.

References

  • 1. Shikha Srivastava, Ranganatha R. Somasagara, Mahesh Hegde, Mayilaadumveettil Nishana, Satish Kumar Tadi, Mrinal Srivastava, Bibha Choudhary & Sathees C. Raghava. Quercetin, a Natural Flavonoid Interacts with DNA, Arrests Cell Cycle and Causes Tumor Regression by Activating Mitochondrial Pathway of Apoptosis
    Scientific Reports volume 6, Article number: 24049 (2016)
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    1. 2. Bożena Pawlikowska-Pawlęga, Wiesław Ignacy Gruszecki, Lucjan Misiak, Roman Paduch, Tomasz Piersiaka, Barbara Zarzykad, Jarosław Pawelec, Antoni Gawrona.  Biochimica et Biophysica Acta (BBA) – Biomembranes.Volume 1768, Issue 9, September 2007, Pages 2195-2204. Modification of membranes by quercetin, a naturally occurring flavonoid, via its incorporation in the polar head group
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    1. 3. Ho Jin Heo, and Chang Yong Lee.  Protective Effects of Quercetin and Vitamin C against Oxidative Stress-Induced Neurodegeneration.  Department of Food Science and Technology, Cornell University, Geneva, New York 14456 J. Agric. Food Chem., 2004, 52 (25), pp 7514–7517
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    1. 4. Bureau G1, Longpré F, Martinoli MG.  J Neurosci Res. 2008 Feb 1;86(2):403-10. Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation.
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    1. 5. Anderson G, Maes M1.Curr Pharm Des. 2014;20(23):3812-47. Oxidative/nitrosative stress and immuno-inflammatory pathways in depression: treatment implications.
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    3. 6. Patil C.S.a · Singh V.P.b · Satyanarayan P.S.V.b · Jain N.K.b · Singh A.b · Kulkarni S.K.a

    Protective Effect of Flavonoids against Aging- and Lipopolysaccharide-Induced Cognitive Impairment in Mice.  Pharmacology 2003;69:59–67

     

Bacopa Monnieri

  • Bacopa is a powerful herb that has been shown to increase memory and cognition. It works by increasing neuroplasticity, or the brain’s ability to transform itself.
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  • As a neuroprotective compound, Bacopa has been found to increase antioxidant enzyme production, including glutathione peroxidase, and was shown to protect against the effects of mercury and aluminum—these effects were found in multiple brain areas including the frontal cortex and hippocampus. Other studies have shown decrease of inflammation in the brain, leading Bacopa to being studied as potential method to prevent Alzheimer’s.
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  • Functionally, bacopa improves both cognition and memory, as well as mood.  Effects on cognition encompass learning, concentration, and multiple types of memory, and occurs with increases in the neurotransmitter acetylcholine. While these effects can take months to develop, bacopa can also be used to quickly reduce anxiety and depression within one hour through mechanisms involving serotonin and dopamine neurotransmitters.
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  • Bacopa has been found to increase neuroplasticity, which refers to the brain’s ability to mold and transform itself at both a microscopic and macroscopic level.  Bacopa contributes to this function in several ways. Most interestingly, it stimulates neuron growth, in particular the arms of the neurons known as “dendrites,” which enable the very important communications between cells. This may contribute to bacopa’s positive learning and memory effects by supporting actual “rewiring” of the brain. In addition, it has been found to increase blood flow to the brain, increase neuronal growth factors, and even augment the electrical signalling between cells. These effects may explain why bacopa can improve memory equally in younger and elderly individuals.

Curcumin

  • Curcumin is a potent antioxidant found naturally in turmeric and ginger. Its effects on the brain include reducing inflammation as well as improving mood. Like quercetin, it has an extremely broad range of activities, and has been shown to reduce pain, protect from multiple cancers and Alzheimer’s, treat inflammatory conditions, and more.

    Curcumin is well studied for its effects of preventing cognitive decline.

    Multiple studies have shown its ability to improve mood, specifically reducing both depression and anxiety. Along with reducing inflammation, it has unique mechanisms to do this, including raising natural synthesis of omega fatty acids necessary for neuronal growth.  Another study found it protects dendrite length, which are the parts of the neurons which make connections to other neurons.

    Other interesting effects of curcumin found in animal studies is increasing fine motor abilities (such as speed of hand movement) and spatial memory. It also protects the brain in times of oxygen and sleep deprivation.

References

  • 1. Soleimani V1.  Phytother Res. 2018 Feb 26. doi: 10.1002/ptr.6054. Turmeric (Curcuma longa) and its major constituent (curcumin) as nontoxic and safe substances: Review.
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  • 2. Baum L.  J Clin Psychopharmacol. 2008 Feb;28(1):110-3. .Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease.
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  • 3. Sanmukhani J1, Phytother Res. 2014 Apr;28(4):579-85. doi: 10.1002/ptr.5025. Epub 2013 Jul 6.Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial.
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  • 4. Esmaily H1, Chin J Integr Med. 2015 May;21(5):332-8. doi: 10.1007/s11655-015-2160-z. Epub 2015 Mar 17.  An investigation of the effects of curcumin on anxiety and depression in obese individuals: A randomized controlled trial.
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  • 5. Wu A1, Noble EE1, Tyagi E1, Ying Z1, Zhuang Y1, Gomez-Pinilla F2.Biochim Biophys Acta. 2015 May;1852(5):951-61. doi: 10.1016/j.bbadis.2014.12.005. Epub 2014 Dec 27.Curcumin boosts DHA in the brain: Implications for the prevention of anxiety disorders.
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  • 6. Moore TL1,2, Somatosens Mot Res. 2018 Feb 15:1-10. Oral curcumin supplementation improves fine motor function in the middle-aged rhesus monkey.
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  • 7. Moore TL1,2.  Chronic curcumin treatment improves spatial working memory but not recognition memory in middle-aged rhesus monkeys.  Geroscience. 2017 Dec;39(5-6):571-584. Epub 2017 Oct 18.
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  • 8. Lu Z1.  Curcumin protects cortical neurons against oxygen and glucose deprivation/reoxygenation injury through flotillin-1 and extracellular signal-regulated kinase1/2 pathway.  Biochem Biophys Res Commun. 2018 Feb 5;496(2):515-522. doi: 10.1016/j.bbrc.2018.01.089. Epub 2018 Jan 17.
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  • 9. Noorafshan A1.  Life Sci. 2018 Feb 15. pii: S0024-3205(18)30071-7. doi: 10.1016/j.lfs.2018.02.021. [Epub ahead of print].  Could curcumin protect the dendritic trees of the CA1 neurons from shortening and shedding induced by chronic sleep restriction in rats?

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