Brain-derived neurotrophic factor (BDNF) and neuroplasticity support supplement*
What is BDNF?
BDNF is an acronym for brain-derived neurotrophic factor. Brain-derived neurotrophic factor is a protein and a member of the neurotrophin family of growth factors that support and promote neuroplasticity, the ability of the adult brain to reorganize its neural network by forming new connections.
How can a BDNF supplement support brain health? To increase brain-derived neurotrophic factor, a healthy diet and exercise are key. Additionally, specific nutrients can support the brain’s natural ability to generate BDNF. BDNF Essentials® is a comprehensive BDNF supplement designed to support the brain’s formation of nerve growth factors, such as brain-derived neurotrophic factor, which promote neuroplasticity, and neurogenesis.
This unique formulation promotes healthy:* Neuroplasticity
Brain cytokine levels
BDNF & neurogenesis (generation of new neurons)
Oxidative stress levels
Cognitive function
Nrf2 (brain antioxidant)
Cell membranes & function
Acetylcholine levels
Cortisol levels
BDNF Essentials supplement mechanisms of action:
NeuroCyto protect™ Blend
Blend of five researched herbs that promote brain-derived neurotrophic factor formation and support healthy cytokine levels.*
Cognition Blend Blend of phosphatidylserine and Citicoline to support healthy cellular membrane function and cortisol levels.* What is the role of BDNF in the brain?
BDNF Essentials® is a comprehensive BDNF supplement designed to support neurological health. This unique formula leverages ingredients that have been shown to aid in the formation of nerve growth factors, such as brain-derived neurotrophic factor. Brain-derived neurotrophic factor is essential in supporting neuron health, neuroplasticity (the ability of the brain to rewire itself after a traumatic brain injury), and neurogenesis (the growth of new neurons).
In addition to supporting cellular neurological health, this comprehensive formulation is also designed to support healthy cytokine levels within the brain, overall cognitive function, modulation of cortisol levels, and to support healthy brain activity with aging. BDNF Essentials® contains targeted herbs, mushrooms, and nutrients, which have been found to provide brain supporting and protective properties for memory, concentration, and cognitive processing. Research has shown that these BDNF supplement ingredients may promote the healthy production of nerve growth factors to support neuroplasticity.
By providing support for overall cognitive function as well as long-term neuron and cellular health BDNF Essentials® can nurture brain health, neuroplasticity, and mental wellness for patients seeking to promote the health of this vital organ.
Clinical research Researched Nutritionals® currently has a clinical human research study underway on BDNF Essentials®, and it will include various clinical and lifestyle measurements so the doctor and patients know what to expect when including this product in their cognitive protocol. Anecdotally, we have had doctors report very positive feedback from many patients.
Tuesday, March 19, 2024
An Open-label Exploratory Study Investigating BDNF Essentials® on Cognition in Healthy Adults with Self-reported Memory Complaints
Friday, March 1, 2024
The State of Glutathione Research
As the major antioxidant in the body, glutathione is essential for human health. With chronic disease, there is an increase in inflammation and oxidative stress leading to an increased need for glutathione. Aging is associated with lower levels of glutathione and increasing levels of oxidative stress.10 Multiple types of infections have been associated with low levels of glutathione including viral infections such as COVID-19, influenza, and HIV.11-13 Chronic infections such as Borrelia infections which impact an increasing number of people are associated with low levels of glutathione.14
Because glutathione is a critical antioxidant in the body, the question becomes how to best supplement. Glutathione can shift rapidly between the reduced and the oxidized state so when taken in a direct form orally it gets oxidized in the stomach, so the active form is not absorbed. The human gastrointestinal tract contains significant amounts of the enzyme GGT, which recycles GSH precursors. This may decrease GSH absorption significantly from oral glutathione supplementation.20 To protect glutathione, liposomes which are lipids surrounding the glutathione, have been developed. Intravenous (IV) glutathione is used by many practitioners in their practice but because of cost and time is difficult to do frequently long term. Transdermal, intranasal, and nebulized glutathione are other forms of supplementation but have less research and less availability. Practitioners also use precursors for glutathione such as N-Acetylcysteine (NAC). Research on glutathione absorption and clinical outcomes are reviewed below to evaluate efficacy of different glutathione supplementation methods. In vivo studies will be the focus to show practitioners how to best support their patients with glutathione supplementation.
Initial research on supplementing oral glutathione was done with the reduced GSH form without any change in the molecule or added lipids in the form of a liposome. In 1992, researchers gave a single dose of 3 grams of GSH to seven people and did not observe an increase in blood GSH levels.21 A randomized double-blind placebo-controlled trial was done in 2011 that had 40 participants given 500 mg twice a day for four weeks.20 Oxidative stress markers were not reduced and there was no increase in total reduced, GSH, oxidized GSSH, or change in ratio of GSH/GSSH.20 Since there were no changes in glutathione or oxidative stress markers, oral glutathione in its unmodified form was not thought to be an option for glutathione supplementation. From these results, companies developed patented liposomal glutathione preparations. Several of these have been studied for absorption and/or clinical symptom improvement. One patented form of liposomal glutathione was researched for 6 months in a randomized controlled trial where half of the participants received a low dose 250 mg/day and half received a high dose of 1000 mg/day.9 Both doses showed increases in glutathione levels with the higher dose showing greater improvements. The high dose of 1000 mg after 6 months showed an increase in GSH (reduced active form) of 30-35% in red blood cells, plasma, and lymphocytes (P<0.05).9 For immune function, natural killer cytotoxicity was measured with a > two fold increase in the high dose group after 3 months (P < 0.05).9 For oxidative stress evaluation a decrease in oxidized to reduced glutathione ratios in whole blood were seen at the end of the study.
Topical or transdermal glutathione is an easy way to supplement glutathione, but the initial research did not support the efficacy of it. Research compared oral liposomal glutathione versus transdermal glutathione in children with autism spectrum disorder who had low baseline levels of glutathione.15 The study was conducted over 8 weeks and the doses of both the transdermal and the oral liposomal glutathione began at ¼ recommended dose and increased weekly until the full dose per weight was given at 4 weeks and that dose was maintained throughout the study.15 The children taking the oral glutathione had significant increases in plasma reduced glutathione along with elevated levels of sulfate, cysteine, and taurine.15(Kern). In the transdermal glutathione group, there were also significant increases in plasma sulfate, cysteine, and taurine levels but not in plasma glutathione levels.15 The results lead to the concern whether transdermal glutathione was sufficient for raising plasma glutathione levels.
Initial research on intravenous (IV) glutathione showed that after an infusion of 2 gms. of glutathione the concentration of both total glutathione and cysteine in the plasma increased significantly.23 Excretion of glutathione in the 90 minutes following infusion increased 300 fold for glutathione and was at a constant rate with a half-life corresponding to 14.1 +/- 9.2 min.23 Subsequent research on intravenous glutathione has focused more on improvement in clinical symptoms than in vivo absorption studies. Two studies done on Parkinson’s patients have shown clinical improvements with IV glutathione given daily for a month, but these clinical improvements returned to baseline after approximately two months without glutathione in both studies.24,25 Clinical studies have compared IV glutathione to oral N-acetylcysteine (NAC) for preventing oxidative stress after coronary angiography which induces oxidative stress damage.26 IV glutathione prevented the increase in oxidative stress markers as predicted but oral NAC had no effect on the oxidative stress markers.26 Based on the research, although limited, it appears that IV glutathione is effectively getting into the blood stream. The concern is how long this effect lasts based on the short half-life.
Both intranasal and nebulized forms of glutathione are available and used primarily for sinus and lung conditions. Absorption studies are minimal. A safety study on intranasal glutathione found it to be helpful for symptoms in 62% of patients with 12% reporting side effects.27 Intranasal glutathione is also being researched for neurodegenerative diseases with its close proximity to the nervous system. A study showed high dose intranasal glutathione to improve Parkinsons’s symptoms, but the results were not statistically significant.28
N-acetylcysteine (NAC) is often used as a supplement to increase glutathione levels. Cysteine is the rate limiting step in glutathione synthesis so the thought is it would lead to an increased production of glutathione. One concern with this is the body’s ability to synthesize glutathione from cysteine and other amino acids decreases with age and with certain chronic diseases especially if they involve liver dysfunction.29 Genetic SNIPS’s including glutathione building and glutathione recycling enzymes can also influence the rate of glutathione production from precursors. Studies of NAC have been inconsistent with showing levels of increased glutathione.29-33 Since the benefits of glutathione include improving immune function and decreasing oxidative stress, NAC has been studied for both functions. Research has shown in specific studies that NAC does not influence immune function.33 or antioxidant function.31 Overall, the research on NAC appears to be limited in terms of being a good method for improving glutathione and supporting multiple glutathione functions.
Glutathione as our primary antioxidant is critical for health. With the toxins in our environment along with high rates of chronic disease and stress, many people are low in this critical nutrient. Because of this, practitioners have searched for ways to elevate glutathione. There is research that shows improvement with targeted forms of oral glutathione in the liposomal form and modified topical glutathione (GSH-CD). Improvements in clinical function have been found with the liposomal oral form. Intravenous glutathione according to research is absorbed and can improve clinical symptoms but the concern is the short half-life and the return of symptoms once the IV glutathione has been stopped. Because of cost and needing to be in a clinical setting, IV glutathione is not practical for daily use. Intranasal glutathione and nebulized glutathione as methods for targeted disease states could be helpful but are not adequately researched at this time. Overall, more research needs to be done to understand how to maximize the supplementation of glutathione to benefit patients.
- Zhang H, Forman HJ. Glutathione synthesis and its role in redox signaling. Semin Cell Dev Biol. 23:722–728.
- Forman HJ. et al. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009;30(1-2):1-12.
- Pastore A. et al. Analysis of glutathione: implication in redox and detoxification. Clin Chim Acta. 2003 Jul 1;333(1):19-39.
- Yuan L. et al. Glutathione in liver disease and hepatotoxicity. Aspects of Med. 2009. 29-41.
- Cantin A et al. Glutathione and Inflammatory Disorders of the lungs. 1991. 169:123-138.
- Guerra C. et al. Glutathione and adaptive immune responses against mycobacterium tuberculosis infection in healthy and HIV infected individuals. PLOS One. 2011.
- Sinha R. et al. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur J Clin Nutr. 2018 Jan;72(1):105-111.
- Morris G. et al. Redox regulation of the immune response. Cell Mol Immunol. 2022 Oct;19(10):1079-1101.
- Richie JP Jr. et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. 2015 Mar;54(2):251-63.
- Maher P. et al. The effects of stress and aging on glutathione metabolism. Ageing Research Reviews. Vol 4(2).
- Nencioni L. et al. Influenza A virus replication is dependent on an antioxidant pathway that involves GSH and Bcl-2. 2003;17:758–760.
- Polonikov A. Endogenous deficiency of glutathione as the most likely cause of serious manifestations and death in patients with the novel coronavirus infection (COVID-19): A hypothesis based on literature data and own observations. ACS Infect. Dis. 2020;6:1558–156.
- Ly J. et al. Liposomal Glutathione Supplementation Restores TH1 Cytokine Response to Mycobacterium Tuberculosis Infection in HIV-Infected Individuals. Interferon. Cytokine Res. 2015;35:875–887.
- Peacock BN. et al. New insights into Lyme disease. Redox Biology. 2015;5:66-70.
- Kern JK. et al. A clinical trial of glutathione supplementation in autism spectrum disorders. Med Sci Monit. 2011;17(12):CR677-CR682.
- Hauser RA. Et al. Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson’s disease. Mov Disord. 2009 May 15;24(7):979-83.
- Tan M. et al. Glutathione system enhancement for cardiac protection: pharmacological options against oxidative stress and ferroptosis. Cell Death Dis. 2023 Feb 16;14(2):131.
- Ghezzi P. et al. Role of glutathione in immunity and inflammation in the lung. Int J Gen Med. 2011;4:105–113.
- Bianchi G. et al. Glutathione kinetics in normal man and in patients with liver cirrhosis. Hepatol. 1997;26:606–613.
- Allen J, Bradley RD. Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. J Altern Complement Med. 2011;17(9):827-833.
- Witschi A. et al. The systemic availability of oral glutathione. Eur J Clin Pharmacol. 1992;43:667–669.
- Sasaninia K. et al. Topical Absorption of Glutathione-Cyclodextrin Nanoparticle Complex in Healthy Human Subjects Improves Immune Response against Mycobacterium avium Antioxidants (Basel). 2023 Jul 2;12(7):1375.
- Aebi S. et al. High-dose intravenous glutathione in man. Pharmacokinetics and effects on cyst(e)ine in plasma and urine. Eur J Clin Invest. 1991 Feb;21(1):103-10.
- Hauser RA. Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson’s disease. Mov Disord. 2009 May 15;24(7):979-83.
- Sechi G. Reduced intravenous glutathione in the treatment of early Parkinson’s disease. Prog Neuropsychopharmacol Biol Psychiatry. 1996 Oct;20(7):1159-70.
- Saitoh T. et al. Intravenous glutathione prevents renal oxidative stress after coronary angiography more effectively than oral N-acetylcysteine. Heart Vessels. 2011 Sep;26(5):465-72.
- Mischley LK. et al. Safety survey of intransal glutathione. The J Alt and Comp Medicine. 2013 19:5, 459-463.
- Mischley LK. et al. Phase IIb Study of Intranasal Glutathione in Parkinson’s Disease. J Parkinsons Dis. 2017;7(2):289-299.
- Schmitt B. et al. Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study. Redox Biology6 (2015): 198-205.
- Treitinger A. et al. Effect of N-acetyl-L-cysteine on lymphocyte apoptosis, lymphocyte viability, TNF-alpha and IL-8 in HIV-infected patients undergoing anti-retroviral treatment. Braz J Infect Dis. 2004 Oct;8(5):363-71.
- Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther. 2014 Feb;141(2):150-9. doi: 10.1016/j.pharmthera.2013.09.006. Epub 2013 Sep 28. PMID: 24080471.
- Paschalis V, Theodorou AA, Margaritelis NV, Kyparos A, Nikolaidis MG. N-acetylcysteine supplementation increases exercise performance and reduces oxidative stress only in individuals with low levels of glutathione. Free Radic Biol Med. 2018 Feb 1;115:288-297. doi: 10.1016/j.freeradbiomed.2017.12.007. Epub 2017 Dec 9. PMID: 29233792.
- Hamzeh N, Li L, Barkes B, Huang J, Canono B, Gillespie M, Maier L, Day B. The effect of an oral anti-oxidant, N-Acetyl-cysteine, on inflammatory and oxidative markers in pulmonary sarcoidosis. Respir Med. 2016 Mar;112:106-11. doi: 10.1016/j.rmed.2016.01.011. Epub 2016 Jan 22. PMID: 26831541.
Monday, February 26, 2024
Quercetin Benefits Chronic Fatigue
Chronic fatigue syndrome is a complex series of symptoms with uncertain etiologies. Quercetin has shown numerous mechanisms of action that might make it a candidate for consideration in cases of chronic fatigue syndrome – antioxidant, anti-inflammatory, immune-modulating, improved exercise endurance, and increased mitochondrial biogenesis and function. Therefore, a well-absorbed form of quercetin was tested for efficacy in individuals suffering from chronic fatigue.
In this study, 78 participants (average age 56; female=42; male=36) complaining of various aspects of chronic fatigue were randomized to receive 250 mg quercetin phytosome or placebo twice daily for two months. Potential participants with an identifiable cause of fatigue like hypothyroidism or anemia were excluded. The primary endpoint was a change from baseline in scores on the Fatigue Impact Scale (FIS-40). Secondary endpoints included sleep quality (measured by the Pittsburgh Sleep Quality Index), quality of life scores, and physical performance and endurance via several physical tests.
At the end of the study, changes in scores on the various tests were compared between the supplement and placebo groups. The quercetin group had significantly greater improvement compared to placebo on the primary endpoint using the FIS-40 score to assess aspects of fatigue. The supplement group also had comparatively and significantly greater improvement in sleep quality and physical performance/endurance. The specific areas of physical performance improvement included number of steps (measured by an armband sensor), gait speed, chair-stand test, and time-up-and-go (the time it takes to stand from an armchair, walk three meters, walk back, and sit down).