Recently, I was asked to be an un-paid beta tester as part of the launch of a supplement line by a friend of mine, nutritional therapist and medical doctor Marc Wagner, the founder of BioFlourish. As a beta tester, I did not receive monetary compensation but received a free bottle of BrainFlō to review.
Fire In the Body, Fire in the Brain
One of the most debilitating symptoms which is universal to autoimmune patients is fatigue, and even more disruptive is the cognitive dysfunction which plagues people with chronic inflammation-mediated disorders. Many systemic disorders with autoimmune pathology, including but not limited to Behçet disease, juvenile idiopathic arthritis, multiple sclerosis (MS), sarcoidosis, scleroderma, Sjögren's syndrome, and systemic lupus erythematosus (SLE) have an element of neurological involvement (Pohl & Benseler, 2013). In fact, researchers state that virtually every neurological symptom can have an autoimmune etiology (Pohl & Benseler, 2013).
Previously, we considered the brain to be immunologically privileged, meaning it was perceived to be able to tolerate the introduction of antigens, or immune-provocating substances which would otherwise incite immune responses, without eliciting an inflammatory immune response. However, this notion was overturned by the recent discovery that the brain has its own lymphatic system, the part of the immune system which transports infection-fighting white blood cells throughout the body, which functions in clearance of β- amyloid plaques and other neurotoxic waste products that accumulate in the central nervous system (Mendelsohn & Larrick, 2013).
Moreover, the idea that the brain was isolated from immune reactions was challenged long ago by insights about microglia cells, a type of macrophage which resides in the brain, engulfs antigens, and produces pro-inflammatory signaling molecules called cytokines. As innate immune cells of the central nervous system, microglia are the first responders when it comes to noxious insults (Baufeld et al., 2017). In addition, microglia are implicated in the neuroinflammation that occurs in many autoimmune disorders such as SLE and MS (Wang et al., 2017).
Taken cumulatively, this research and the findings on central nervous system lymphatic vessels lining the dural sinuses suggests that the brain participates in immunological surveillance and can in fact generate adaptive immune responses (Louveau et al., 2015). In other words, if there is a fire in the body, there is a fire in the brain, and these discoveries crystallize an anatomical link between disorders of immune dysfunction and neurodegeneration.
It's no mystery, then, why so many people with autoimmune disease experience comorbid psychiatric illnesses such as anxiety and depression, which are inextricably linked to brain inflammation. It's also no wonder that so many people with autoimmune disease can experience problems with mental clarity, word recall, and cognitive sharpness given the inflammatory fire in the body that also permeates the brain.
Luckily, we have natural agents in our arsenal we can use to mitigate neurological inflammation, optimize neurotransmitter production, engender neurotrophic and neuroprotective effects, and improve circulation to the brain, all of which may improve mental stamina and focus and alleviate disruptive mental symptoms.
Benefits of BrainFlō Herbal Ingredients
As a long time worshiper at the altar of plant medicine, my favorite ingredients in BrainFlō are the herbs rhodiola rosea and gingko biloba, which are classified as adaptogenic herbs. Botanical adaptogens enhance the physiological state of non-specific resistance and exert a normalizing effect irrespective of the nature of the stressors encountered.
Venerated as the "gift of the spirits" by traditional Siberian populations, Rhodiola has been used as a medicinal agent in both traditional Russian and Tibetan culture for over a millenium. When Rhodiola was taken by foreign students during a stressful examination period for twenty days, performance on tests of physical fitness, mental fatigue and neuro-motor skills significantly improved and sense of well-being was also significantly enhanced (Spasov et al., 2000). Another study conducted on young cadets revealed that a single dose of Rhodiola elicited a pronounced antifatigue effect (Shevtsov et al., 2003).
Yet another study of low-dose treatment with a standardized extract of rhodiola in night-shift physicians showed that the herb significantly improved perceptive and cognitive cerebral functions, as illustrated by tests of "associative thinking, short-term memory, calculation and ability of concentration, and speed of audio-visual perception" (Darbinyan et al., 2000). Studies have likewise elucidated that rhodiola improves energy and increases attention in patients with stress-related fatigue (Olsson et al., 2009).
In addition to its anti-fatigue, neuroprotective, and adaptogenic effects, rhodiola also exhbits antidepressant, anxiolytic, and antimicrobial characteristics. Extracts of this herb have even been proven to significantly reduce symptoms of mild-to-moderate depression, insomnia, emotional lability, and somatization when administered for six weeks (Darbinyan et al., 2007).
On the other hand, research indicates that gingko biloba elicits favorable effects "on cerebral circulation and neuronal cell metabolism, hemorrheology and microperfusion, the elimination of free radicals, the muscarinic cholinergic system, and the learning process" (Kanowski et al., 1997, p. 4). In other words, gingko supports cerebral blood flow and oxygenation as well as neurotransmission of acetylcholine, the neurotransmitter that promotes learning and encoding of memories (Hasselmo, 2006).
In fact, acetylcholine esterase inhibitors are the only pharmaceutical agents approved by the Food and Drug Administration (FDA) to impede the gradual, progressive cognitive decline that is the hallmark of Alzheimer's disease (Akhodzadeh et al., 2003). These drugs work by enhancing the half-life of acetylcholine in the synapse by preventing its degradation by the enzyme cholinesterase. One study found that gingko biloba has efficacy in Alzheimer's type dementia as well as dementia of the multi-infarct type (memory loss due to multiple strokes), and it may work via a similar mechanism (Kanowski et al., 1997). The effects of ginkgo may complement those of rhodiola, as revealed by a study which showed that the combination significantly improved short-term working memory accuracy compared to either used alone (Al-Kuraishy, 2015).
Benefits of BrainFlō Nutraceutical Ingredients
BrainFlō is part of the patented Restore & Adapt Protocol™, which delivers methyl donors, choline donors, and amino acid precursors which support the synthesis of neurotransmitters including dopamine, acetylcholine, and norepinephrine.
Alpha-glycerophosphocholine (alpha-GPC), for instance, delivers high levels of choline to nerve cells in the brain and serves as a precursor for membrane phospholipids, which form the amphiphilic lipid bilayers of cell membranes (Barbagallo Sangiorgi et al., 1994). Therefore, it improves the function of neuronal membranes and confers protection. Alpha-GPC crosses the blood brain barrier and directly increases the production of acetylcholine, supporting cholinergic neurotransmission needed for cognition (Barbagallo Sangiorgi et al., 1994)..
It has been shown to be effective in the cognitive recovery of patients with acute stroke or transient ischemic attack (Barbagallo Sangiorgi et al., 1994). In numerous controlled clinical studies, alpha-GPC has been shown to produce positive clinical outcomes in dementia irrespective of its etiology and to prevent memory deficits engendered by the anti-nausea drug scopolamine (Hyoscine) (Barbagallo Sangiorgi et al., 1994). In animal models, it also promotes learning and memory in a dose-dependent fashion (Barbagallo Sangiorgi et al., 1994).
Acetyl-L-carnitine (ALCAR) is an acetylated form of carnitine, a fatty acid shuttle that navigates across the blood brain barrier and helps neurons generate more energy through a process known as β-oxidation. ALCAR optimizes mitochondrial bioenergetics, or the operations of the energy powerhouse organelles of the cell, as well as promotes excretion of oxidative products (Onofrj et al., 2013). ALC can offer neurotherapeutic benefits in in neuropsychiatric disorders via anti-inflammatory, antioxidant, and metabolic mechanisms (Soczynska et al., 2008). For instance, when administered with another mitochondrial supportive nutrient in an animal model of Parkinson's disease, ALCAR reduces levels of brain lipid peroxidation ("rusting" of fats in the brain), enhanced motor performance, and increased synthesis of adenosine triphosphate (ATP), the energy currency of the cell (Zaitone et al., 2012).
ALCAR has consistently been shown to improve peripheral neuropathies in diabetic neuropathy, neuropathy secondary to chemotherapy or compression, and HIV and antiretroviral therapy-induced neuropathy (Onofrj et al., 2013). It also exerts neurotrophic effects, meaning that it supports the growth, differentiation, and survival of developing and mature neurons alike (Onofrj et al., 2013). ALCAR donates acetyl groups for synthesis of acetylcholine, which is essential for muscular contraction and as previously discussed, aspects of cognition such as attention, learning, and memory consolidation. Acetylcholine also increases long-term potentiation, a form of synaptic plasticity that involves the strengthening of synapses between neurons that plays a role in acquisition and recall (Lynch, 2004).
L-tyrosine is the amino acid building block of dopamine, the neurotransmitter of motivation. It is also the precursor to other catecholamines: namely, epinephrine (adrenaline) and norepinephrine (noradrenaline). Stress enhances release of epinephrine and norepinephrine from the adrenal medulla, which can deplete their levels. Norepinephrine functions in the neural tracts that respond to stress, and exhaustion of norepinephrine levels, which may accompany adrenal burn-out, are correlated with stress-related impairments in performance (Salter, 1989).
It has been reported in the literature that L-tyrosine can attenuate the decline in cognitive function that accompanies physical stressors such as sleep deprivation, cold stress, high-altitude stress, and negative pressure stress (the last of which occurs with space flight) (Young, 2007). For example, L-tyrosine enhanced aspects of cognitive function including memory and a tracking ability when administered to military cadets during a demanding combat training course (Deijen et al., 1999).
Other researchers hypothesize that tyrosine may prevent the anxiety, stress, mood deterioration, and performance decrement that occur in stressful scenarios such as military sustained operations (Owasoyo et al., 1992). Scientists conclude that, "tyrosine may, under operational circumstances characterized by psychosocial and physical stress, reduce the effects of stress and fatigue on cognitive task performance" (Deijen et al., 1999, p. 203). Tyrosine also improves working memory while multitasking (Thomas et al., 1999).
BrainFlō contains methylfolate (5-MTHF) as Quatrefolic®, which supports healthy methylation in the body. Methylation is the attachment of simple one-carbon methyl group tags (CH3) to DNA molecules, which activates or silences gene expression. This form of vitamin B9 is bioavailable to those of us with polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene C677T, which is associated with assorted autoimmune diseases and mood disorders such as depression and schizophrenia (Cevik et al., 2014; Stover et al., 2017).
Folate serves innumerable fundamental purposes in the body, including playing roles in DNA synthesis, cell growth and development, as well as erythropoiesis, or the production of red blood cells (Koury & Ponka, 2004; Mahmood, 2013). Brain folate deficiency has been illuminated in studies to contribute to both neuropsychiatric and neurodegenerative disease (Stover et al., 2017). Deficiency of folate may adversely affect metabolism of monoamines such as serotonin and norepinephrine, which can exacerbate depression (Bottiglieri, 1996). In fact, folate is recognized as an adjunct therapy to pharmaceutical antidepressant drugs by the American Psychiatric Association (Freeman, 2009). Parenteral folate has even been shown to improve white matter morphology and improve neurological outcomes in some studies, underscoring the crucial role of this vitamin in brain health (Stover et al., 2017).
Vitamin B12, also known as cobalamin, is also important to the functioning of the nervous system. Late-stage B12 deficiency presents with neuropsychiatric manifestations such as dementia, neuropathy (weakness, numbness, and pain in the extremities due to peripheral nerve damage), and myelopathy (loss of spinal cord activity) (Ralapanawa et al., 2015). The most common manifestation of B12 deficiency is subacute combined cord degeneration (SACD), or degeneration of the posterior and lateral columns of the spinal cord (Ralapanawa et al., 2015). When subjects with cobalamin deficiency are administered B12 supplements, cognitive and cerebral functions improve (van Asselt, 2001).
BrainFlō contains methylcobalamin, the biologically active form which is required as a cofactor for the enzymes methionine synthase, which is used in the synthesis of DNA purines and pyrimidines, and L-methyl-malonyl-CoA mutase, which converts methylmalonyl CoA to succinyl CoA (O'Leary & Samman, 2010). A defect in this latter reaction, with the accumulation of methylmalonyl CoA due to inability of this enzyme to function, is responsible for the neurological detriments incurred due to B12 deficiency (O'Leary & Samman, 2010).
In addition, both folate and B12 are required to methylate homocysteine into methionine and to create the body's primary methyl donor, S-adenosylmethionine (Bottiglieri, 1996). Therefore, lack of these nutrients can cause elevations in homocysteine, which may play a role in neurological disorders and psychiatric aberrations such as depression, dementia, and demyelinating myelopathy due to its neurotoxic potential (Bottiglieri, 1996). Methylation abnormalities are observed in a sizable portion of the population, and an even greater proportion of the chronic illness community, so the inclusion of these nutrients is well-warranted.
Vitamin B9 and B12, both of which are contained in BrainFlō, are best administered in tandem. When given as a combination to Indian children, these B vitamins elicited significant improvement in gross motor skills and problem solving. However, either vitamin alone had no effect on any of these outcomes (Kvestad, et al., 2015).
BrainFlō is a well-designed formulation with empirically validated ingredients, many of which have studies demonstrating positive effects for energy, learning, memory, and mood, as well as producing desirable neurobiological effects.
After college, I worked as a research assistant under a PhD candidate who was awarded the Wenner-Gren Foundation Dissertation Fieldwork Grant, researching nootropics through the lens of medical anthropology. We explored medical, recreational, and academic use of stimulant drugs as a form of cosmetic neurology or cognitive enhancement, and the trajectory of American culture and higher education towards pharmaceuticalization. I witnessed firsthand how people are desperate for quick-fix agents to artificially augment their mental capacities in increasingly competitive academic and corporate settings. However, there is a better way.
The natural ingredients in BrainFlō are biocompatible, natural agents that are "crafted to help support short and long-term memory, improve concentration and circulation to the brain, support neurotransmitter production, help bridge genetic gaps in methylation, and serve as a neuroprotective agent for your hard-working brain cells" (Wagner, 2017). I noticed improvements in energy and focus the first time I took BrainFlō, and it helped me during twelve-hour days at a medical conference to actively engage with the material whereas I was nodding off at the last one I attended. I also noticed a significant reduction in the frequency of my migraines, which is a game-changer for me.
The simple philosophy Marc adopted when designing this product: "Restoration & Adaptation. Replenishment & Resilience" perfectly encapsulates the mechanisms underlying the ingredients in BrainFlō, and I give my whole-hearted endorsement to those seeking to give their brain a little extra love.
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Consult a physician before adding any supplement to your regimen and read my medical disclaimer.
Al-Kuraishy, H.M. et al. (2015). Central additive effect of Ginkgo biloba and Rhodiola rosea on psychomotor vigilance task and short-term working memory accuracy. Journal of Intercultural Ethnopharmacology, 5(1), 7-13. doi: 10.5455/jice.20151123043202.
Baufeld, C. et al. (2017). Differential contribution of microglia and monocytes in neurodegenerative diseases. Journal of Neural Transmission (Vienna), [Epub ahead of print]. doi: 10.1007/s00702-017-1795-7
Barbagallo Sangiorgi, G. et al. (1994). alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial. Annals of the New York Academy of Science, 717, 253-269.
Cevik, B. et al. (2014). Association of methylenetetrahydrofolate reductase gene C677T polymorphism with multiple sclerosis in Turkish patients. Journal of Investigative Medicine, 62(8), 980-984. doi: 10.1097/JIM.0000000000000107.
Darbinyan, V. et al. (2000). Rhodiola rosea in stress induced fatigue--a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine, 7(5), 365-371.
Darbinyan, V. et al. (2007). Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nordic Journal of Pyschiatry, 61, 343-348.
Deijen, J.B. et al. (1999). Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course. Brain Research Bulletin, 48(2), 203-209.
Freeman, M.P. (2009). Complementary and alternative medicine (CAM): considerations for the treatment of major depressive disorder. Journal of Clinical Psychiatry, 70(5), 4-6.
Hasselmo, M.E. (2006). The Role of Acetylcholine in Learning and Memory. Current Opinions in Neurobiology, 16(6), 710–715.
Kanowski, S. et al. (1997). Proof of efficacy of the Ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Phytomedicine, 4(1), 3-13.
Koury, M.J., & Ponka, P. (2004). New insights into erythropoiesis: the roles of folate, vitamin B12, and iron. Annual Reviews in Nutrition, 24, 105-131.
Kvestad, I. et al. (2015). Vitamin B12 and Folic Acid Improve Gross Motor and Problem-Solving Skills in Young North Indian Children: A Randomized Placebo-Controlled Trial. PLoS One, https://doi.org/10.1371/journal.pone.0129915.
Louveau, A. et al. (2015). Structural and functional features of central nervous system lymphatic vessels. Nature, 523(7560), 337-341. doi:10.1038/nature14432.
Lynch, M.A. (2004). Long-term potentiation and memory. Physiological Reviews, 84(1), 87-136.
Mahmood, L. (2014). The metabolic processes of folic acid and Vitamin B12 deficiency. Journal of Health Research & Reviews, 1(1), 5-9. doi: 10.4103/2394-2010.143318
Mendelsohn, A.R., & Larrick, J.W. (2013). Sleep facilitates clearance of metabolites from the brain: glymphatic function in aging and neurodegenerative diseases. Rejuvenation Research, 16(6), 518-523. doi: 10.1089/rej.2013.1530.
O'Leary, F., & Samman, S. (2010). Vitamin B12 in Health and Disease. Nutrients, 2(3), 299-316. doi: 10.3390/nu2030299
Olsson, E.M. et al. (2009). A randomized, double-blind, parallel-group study of the standardized extract shr-5 ont he roots of Rhodiola rosea in the treatment of subjects with stress related fatigue. Planta Medicine, 75, 105-112.
Onofrj, M. et al. (2013). Acetyl-L-carnitine: from a biological curiosity to a drug for the peripheral nervous system and beyond. Expert Reviews in Neurotherapeutics, 13(8), 925-936. doi: 10.1586/14737175.2013.814930.
Owasoyo, J.O. et al. (1992). Tyrosine and its potential use as a countermeasure to performance decrement in military sustained operations. Aviation Space and Environmental Medicine, 63(5), 364-369.
Pohl, D., & Benseler, S. (2013). Systemic inflammatory and autoimmune disorders. Handbook of Clinical Neurology, 112, 1243-1252. doi: 10.1016/B978-0-444-52910-7.00047-7.
Ralapanawa, D.M.P.U.K. et al. (2015). B12 deficiency with neurological manifestations in the absence of anaemia. BMC Research Notes, 8, 458. doi: 10.1186/s13104-015-1437-9
Salter, C.A. (1989). Dietary tyrosine as an aid to stress resistance among troops. Military Medicine, 154(3), 144-146.
Shevtsov, V.A. et al. (2003). A randomized trial of two different doses of a SHR-5 Rhodiolarosea extract versus placebo and control of capacity for mental work. Phytomedicine, 10(2-3), 95-105.
Spasov, A.A. et al. (2000). A double-blind, placebo-controlled pilot study of the stimulatingand adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination periodwith a repeated low-dose regimen. Phytomedicine, 7(2), 85-89.
Soczynska, J.K. et al. (2008). Acetyl-L-carnitine and α-lipoic acid: possible neurotherapeutic agents for mood disorders? Expert Opinion on Investigational Drugs, 17(6):827-43. doi: 10.1517/135437126.96.36.1997.
Stover, P.J., Durga, J., & Field, M.S. (2017). Folate nutrition and blood–brain barrier dysfunction. Current Opinion in Biotechnology, 44, 146-152.
Thomas, J.R. et al. (1999). Tyrosine Improves Working Memory in a Multitasking Environment. Pharmacology Biochemistry and Behavior, 64(3), 495-500.
van Asselt, D.Z. et al. (2001). Cobalamin supplementation improves cognitive and cerebral function in older, cobalamin-deficient persons. Journal of Gerontology and Biological Science: Medical Science, 56(12), M775-M779.
Wagner, M. (2017). Introducing BrainFlō(TM). Retrieved from http://bioflourish.com/brainflo/
Wang, J. et al. (2017). Microglia activation induced by serum of SLE patients. Journal of Neuroimmunology, 310, 135-142. doi: 10.1016/j.jneuroim.2017.07.010.
Young, S.N. et al. (2007). L-Tyrosine to alleviate the effects of stress? Journal of Psychiatry & Neuroscience, 32(3), 224.
Zaitone, S.A. et al. (2012). Acetyl-L-carnitine and α-lipoic acid affect rotenone-induced damage in nigral dopaminergic neurons of rat brain, implication for Parkinson's disease therapy. Pharmacology, Biochemistry, & Behavior, 100(3), 347-360. doi: 10.1016/j.pbb.2011.09.002.