Voluntastrols® Clinical Support Information

  • Neuro-Inflammation & Depression

    Anti-inflammatory and inflammationpreventative via modulation of the immune response

  • Neurovascular Network Health

    Engineered to navigate the blood brain barrier/ neurovascular network

  • Novel Neuroprotective Mechanism

    Preventing neuron death from Calcium ion overload by modulation of mitochondrial membrane potential.

  • Brain Derived Neurotrophic Factor

    Increasing levels of BDNF & restoring hippocampus function and production of BDNF.

  • Synergistic Therapeutic Actions

    Multiple therapeutic actions working synergistically to prevent & ameliorate mental fatigue, the effects of stress, low mood and depression

The prevalence of psychiatric disorders is steadily increasing, with depression currently the fourth leading cause of disability worldwide and is expected to become the second most prevalent disease, after coronary heart disease by 2020.Theories have evolved beyond the “serotonin hypothesis” regarding the causes of low mood and depression (Cowen & Browning 2015), with chronic inflammation now increasingly recognised as a risk factor and a key aspect in the pathophysiology of the mental health disorders. A substantial proportion of people with depression, exhibit elevated concentrations of circulating inflammatory markers such as pro-inflammatory cytokines, thus reinforcing this current theory.

NEURO-INFLAMMATION AND DEPRESSION

A 2015 review of 200 existing papers on depression and inflammation, in the American Journal of Psychiatry, supports the concept that chronic inflammation fuels depression.The authors noted that inflammation was not only linked to physical health issues, such as diabetes and cancer, but systemic inflammation is also linked to mental health issues such as depression. They observed that among the patients suffering from depression, concentrations of two inflammatory markers (CRP and IL-6) were elevated by up to 50 percent. The study also found that depression caused by chronic inflammation is resistant to traditional therapy methods (Kiecolt-Glaser, 2015), as the heterogeneity of depressive illnesses creates issues with current medications, as the therapeutic actions of these drugs are based upon monoamine neurotransmitter (e.g. serotonin, dopamine) modulation, rather than targeting the underlying neurobiological pathophysiology (Ross et al. 2017).Neurotransmitters remain an important factor in mental health regulation, with roughly 90 percent of serotonin produced in the gut, gastrointestinal inflammation severely impacts the production and absorption of important neurotransmitters. Chronic gastrointestinal inflammation places stress on the microbiome in the gut, and elevated levels of inflammatory markers (cytokines) in the blood, increase the permeability of the blood-brain barrier, which allows rouge molecules to influence brain function, and is linked to anxiety, depression, and memory loss (Clapp et al. 2017).

A substantial body of research and evidence now demonstrates bidirectional relationships between the brain and behaviour with immune function and vice versa. For example, depressed patients consistently display evidence of elevated inflammatory cytokine levels and the administration of inflammatory cytokines in healthy subjects is associated with increased depressive symptoms, by inducing inflammation, which in turn creates mood disturbance (Clapp et al. 2017).

Neurogenesis is the process in which new-born neurons are generated, however the negative effects of neuroinflammation on neurogenesis could lead to impaired survival and proliferation of new neurons (Calabreze 2014). Therefore reducing or preventing neuroinflammation is crucial to allow neurogenesis, and all its benefits, to occur. Inflammation is the body’s response to stress – whether from diet, lifestyle, environment or trauma. The neuro phyto-actives in Voluntastrols not only help to normalise, or ameliorate, the pathological consequences of the negative impact of inflammation on brain structure and function, but they also perform a key role in the modulation of the inflammatory response, thereby preventing chronic inflammation from occurring in the first place.Increasingly, epidemiological and experimental studies demonstrate that modulation of the inflammatory response by natural phytomolecules such as Voluntastrols play an important role in the prevention, mitigation, and treatment of many chronic inflammatory diseases – including depression. The neuro phyto-actives in Voluntastrols are extremely effective at regulating the inflammatory response through several mechanisms involving the:
• modulation of inflammatory signalling
• reduction of inflammatory molecule production
• diminishing recruitment and activation of inflammatory cells
• regulation of cellular function
• antioxidative properties (Pan et al. 2010).
Neurovascular Network Health

The concept that escalating inflammation of the brain is a common factor in neurodegenerative diseases and various brain/mood disorders, has gained much attention particularly in relation to chronic inflammation. However the theory that the brain was self contained and separate from the body’s immune system created doubt regarding inflammatory response mechanisms within the brain. Neuroimmunologist Michal Schwarz, has overturned the misconception that the brain is an autonomous organ, and has bought revolutionary understanding to light regarding brain health and repair, which has in turn lead to closer examination of the concept that the central nervous system (CNS) lacked a lymphatic drainage system. A group of neuroscientists led by Jonathan Kipnis and Antoine Louveau at The University of Virginia have shown for the first time, that the CNS is connected to the peripheral immune system through a network of lymphatic vessels present in the meninges that enclose the brain and the spinal cord. With emergence of more and more evidence, it is clear that the immune system in the CNS is much more evolved and sophisticated than previously thought and the discovery of the active lymphatic system surrounding the brain and CNS has even been referred to as a “virtual secondary lymphoid organ” (Negi & Das, 2017).

Voluntastrols support and improve Neurovascular Network Health by:
• Avoiding ß-amyloid induced neuron injury and death
• Modulating of pro-inflammatory cytokines
• Inhibiting activation of microglia and astrocyte as neuroprotective mechanisms

Novel Neuroprotective Mechanism

Mitochondrial calcium overload is a key factor in neuronal cell death and furthermore it is strongly implicated in progression of neurodegenerative diseases. A key driving force of calcium overload in the mitochondria is mitochondria membrane potential.

Put simply the membrane potential can be seen as the mitochondrial gatekeeper controlling the flow of calcium ions in and out of the mitochondria depending on the potential difference across the membrane i.e. the charge difference across the membrane will determine the direction of flow of ions, so even a small change of membrane potential can flip this from positive to negative and change the polarization state of the membrane and changing the direction of ion flow. Calcium overload causes neuron apoptosis.

Voluntastrols’ modulation of mitochondria membrane potential can be viewed as a novel mechanism for neuroprotection and prevention of neuronal cell death from brain insults. As it has been demonstrated that even a small mitochondrial depolarization is sufficient to prevent mitochondrial calcium overload and the subsequent apoptosis.

BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF)
& THE BDNF-TRKB PATHWAY

Brain-derived neurotrophic factor (BDNF) promotes the survival and differentiation of selected neuronal populations of the peripheral and central nervous systems. BDNF participates in axonal growth, pathfinding and in the modulation of dendritic growth and morphology. It is a major regulator of synaptic transmission and plasticity at adult synapses in many regions of the CNS. The versatility of BDNF is emphasised by its contribution to a range of adaptive neuronal responses including:
• long-term potentiation
• long-term depression
• certain forms of short-term synaptic plasticity
• homeostatic regulation of intrinsic neuronal excitabilityRecent decades have increasingly seen evidence that indicates that the pathophysiology of major depressive disorder involves BDNF. BDNF, one of the most widely distributed neurotrophins, is involved in the pathophysiology and treatment of depression by binding with, and activating tropomyosin-related kinase receptor B (TrkB).BDNF promotes neuronal survival and maturation, as well as plasticity during development and adulthood (LopezMunoz & Alamo 2011). Low levels of BDNF are linked with:
• depression (the length of depression and the depressive symptoms)
• Alzheimer’s disease
• accelerated aging
• poor neural development
• neurotransmitter dysfunction
• obesityIn addition, levels of BDNF have been shown to correlate with human learning, memory and cognitive function (Spencer, J. 2010).The neuro phyto-actives contained in Voluntastrols are shown to activate BDNF, increasing the levels in the brain of this important protein. Importantly, these phytomolecules are also involved in the maintenance of the hippocampal BDNF-TrkB pathway. With the hippocampus playing a key role in stress, learning and memory processes in depression, the three-fold effect Voluntastrols have in:
• increasing levels of BDNF
• improving the BDNF-TrkB signalling in the hippocampus
• improving Adult Hippocampus Neurogenesis (AHN) ensures a promising multi-faceted approach to managing depression and brain health.

SYNERGISTIC THERAPEUTIC ACTIONS

The neuro phyto-actives found in Voluntastrols provide synergistic therapeutic value due to the complex combination of beneficial compounds scientifically formulated, in stark contrast to the conventional medicine approach of isolating individual chemicals with a narrow focus and therapeutic index. The neuro phyto-actives found in Voluntastrols, have wide-ranging therapeutic actions, such as protecting vulnerable neurons which supports neuronal function to improve memory and learning, and enhancing existing neuronal function and neuronal regeneration, to prevent and reduce the risk of age-related neurodegenerative disorders (Camandola, Plick & Mattson, 2018). The active molecules also activate intracellular signalling pathways, providing positive support for neuronal plasticity, cellular stress responses and cell resilience (Ramos-Hryb et. Al. 2018). Adding to these remarkable benefits, some of the active constituents found in Voluntastrols have been found to “possess a stronger neuroprotective action than antioxidant vitamins” (Kumar & Khanum, 2012).Due to the common and unpleasant side effects of conventional antidepressant medication, there has been great interest in plant based anti-inflammatory and neuroprotective compounds. Voluntastrols have a strong safety profile, as the constituents are naturally occurring in plants with a long history of human consumption. The issue lies in that these neuro phyto-actives are deficient in the majority of people’s diets, therefore the body’s mechanism for preventing (and ameliorating)

 

Inflammation is not functioning as it should. Voluntastrols work to assist the body in resolving chronic inflammation, rather than targeting and altering one neurotransmitter pathway. Voluntastrols’ leading experts compare this to the analogy of a leaky tyre. Rather than simply putting air into the tyre everyday to keep it pumped up, Voluntastrols are akin to repairing the leak and then improving & maintaining the ongoing condition of the tyre.The neuro phyto-actives in Voluntastrols are deficient in the modern diet due to monocultures, pesticides, fungicides, pre- and post-harvest techniques and modern processing techniques. Compounding the effect of this deficiency are diets high in processed, inflammatory foods which are becoming the norm. Voluntastrols provide an evidenced based, fast acting, highly bioavailable, synergistic alternative to current approaches to treating, managing and preventing mental health issues.

REFERENCES

Bahramsoltani, R., Farzaei, M.H., Farahani, M.S. & Rahimi, R. (2015) Phytochemical constituents as future antidepressants: a comprehensive review, Reviews in the neurosciences 26(6), 699-719.Bensonet al(2017)Effectsof acutesystemicinflammation on the interplaybetween sadmood and affectivecognition, TranslationalPsychiatry7:1281.

Calabrese et al (2014) Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity, Frontiers in Cellular Neuroscience, Volume 8, 134.

Camandola, S., Plick, N. & Mattson, M.P., (2018) Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease, Neurochemical Research.

Cowen PJ, Browning M. (2015)What has serotonin to do with depression? World Psychiatry 14(2):158-160.

Kiecolt-Glaser, J.K., Derry, H.M. & Fagundes, C.P. (2015) Inflammation: Depression Fans the Flames and Feasts on the Heat, American Journal of Psychiatry 172:11, 1075-1091.

Li, J., Zhou, Y., Liu, B.B., Liu, Q., Geng, D., Weng, L.J., Yi, L.T., (2013).

Lopez-Munoz, F. & Alamo, C. (2011) Neurobiology of Depression, Series: Frontiers in Neuroscience, CRC Press. Negi, N. & Das, B.K. (2017) CNS: Not an immunoprivilaged site
anymore but a virtual secondary lymphoid organ, International Reviews Of Immunology, 37:1, 57-68.Kumar, G.P. & Khanum, F. (2012) Neuroprotective potential of phytochemicals, Pharmacognosy Review, 6(12): 81–90. Pan, M.H., Lai, C.S., & Ho, C.T., (2010) Anti-inflammatory activity of natural dietary flavonoids, Royal Society of Chemistry, Food and Function, Volume 1, no. 1, pp. 15–31.Pathak, L., Agrawal, Y. & Dhir, A. (2016) Natural polyphenols in the management of major depression, Expert Opinion on Investigational Drugs, 22:7, 863-880.Ramos-Hryb, M.P., Cunha, M.P., Kaster, M.P. & Rodrigues, A.S. (2018) Studies in Natural Products Chemistry, Chapter 6 – Natural Polyphenols and Terpenoids for Depression Treatment: Current Status, Pg 181-221, Volume 55, Elsevier B.V.Ross, R.A., Foster, S.L. & Ionescu, D.F. (2017) The role of chronic stress in Anxious Depression: Chronic Stress, Volume 1, SAGE Publications Inc.Spencer, J. (2010) Beyond antioxidants: the cellular and molecular interactions of flavonoids and how these underpin their actions on the brain, Proceedings of the Nutrition Society, Volume 69, 244-260.