May 15, 2023 – Dr. Emek Blair, Ph. D.

Glutathione is Critical for Longevity

emekblair1stg on May 15, 2023

Glutathione is important for your antioxidant system that plays a crucial role in maintaining cellular health and preventing oxidative damage. Oxidative damage is a key driver of aging, and therefore, the role of glutathione in longevity has been extensively studied.

Several studies have suggested that glutathione levels decline with age and that this decline is associated with an increased risk of age-related decline. In addition, several studies have shown that boosting glutathione levels through supplementation or other interventions can improve longevity.

For example, a study published in the Journal of Nutrition found that supplementation with N-acetylcysteine (a precursor to glutathione) eliminated negative effects of oxidative stress, even when they were exposed to high levels of oxidative stress. Another study published in the Journal of the American Geriatrics Society found that higher glutathione levels were associated with maintaining physical function with aiding.

Moreover, a review published in the journal Aging Cell suggested that maintaining optimal levels of glutathione could help delay the aging process. The review also noted that several interventions, such as caloric restriction, exercise, and supplementation to increase glutathione, improve longevity.

In conclusion, glutathione is critical for longevity due to its role in preventing oxidative damage, and maintaining cellular health. Several studies have shown that boosting glutathione levels through supplementation or other interventions can improve longevity.

References

Richie JP Jr, Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA. Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J. 1994 Dec;8(15):1302-7. doi: 10.1096/fasebj.8.15.8001745. PMID: 8001745.
Schipper HM. Glutathione synthesis and its role in aging and disease. Ann N Y Acad Sci. 1998 Nov 20;854:27-42. doi: 10.1111/j.1749-6632.1998.tb09845.x. PMID: 9928374.
Stadtman ER. Protein oxidation and aging. Free Radic Res. 2006 Jul;40(7):1250-8. doi: 10.1080/10715760600822239. PMID: 17015261.
Schafer FQ, Buettner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med. 2001 May 15;30(11):1191-212. doi: 10.1016/s0891-5849(01)00480-4. PMID: 11368918.
Hagen TM, Wierzbicka GT, Bowman BB, et al. Fate of dietary glutathione: disposition in the gastrointestinal tract. Am J Physiol. 1990;259(4 Pt 1):G530-G535. doi:10.1152/ajpgi.1990.259.4.G530
Lang CA, Mills BJ, Mastropaolo W, Liu MC. Blood glutathione decreases in chronic diseases. J Lab Clin Med. 2000 Oct;136(4):270-6. doi: 10.1067/mlc.2000.109

Magnesium and Longevity: How a Mineral Can Impact Your Lifespan

emekblair1stg on May 15, 2023

Magnesium is an essential mineral that plays a vital role in many of the body’s biochemical processes. It is required for the proper functioning of muscles, nerves, and the immune system. In addition to these important functions, magnesium has also been shown to have anti-aging properties.

Aging is a complex process that involves multiple cellular and molecular changes that occur over time. One of the primary causes of aging is oxidative stress, which is the imbalance between the production of reactive oxygen species (ROS) and the body’s ability to detoxify them. ROS are produced during normal metabolic processes, and excessive ROS production can lead to cellular damage and accelerated aging.

Magnesium has been shown to be critical to your antioxidant system that help to reduce oxidative stress and protect cells from damage. Studies have found that magnesium is critical to the system that can scavenge free radicals and prevent lipid peroxidation, which is a process that damages cell membranes and leads to cell death (1). This makes magnesium an important nutrient for maintaining healthy cells and reducing the risk of age-related diseases.

Another way in which magnesium can help to slow down the aging process is by supporting the body’s energy production. Magnesium is required for the production of ATP (adenosine triphosphate), which is the energy currency of the body. ATP is used to power many of the body’s processes, including muscle contractions, nerve impulses, and the synthesis of proteins and other molecules. As we age, the body’s ability to produce ATP decreases, which can lead to fatigue, reduced muscle strength, and other symptoms of aging.

Research has shown that magnesium supplementation can support ATP production and reduce the risk of age-related decline in muscle function (2). In one study, older adults who took magnesium supplements for 12 weeks had strong muscle strength and physical performance (3). This suggests that magnesium may be an important nutrient for maintaining muscle function and reducing the risk of falls and other age-related injuries.

Magnesium also plays a role in maintaining healthy bones. As we age, bone density decreases, which can lead to injury. Magnesium is required for the absorption and metabolism of calcium, which is a key mineral for bone health. Studies have found that magnesium supplementation can improve bone density and reduce the risk of fractures in older adults (4).

In addition to its physical effects, magnesium may also have cognitive benefits that can help to reduce age-related cognitive decline. Magnesium is required for the production of neurotransmitters, which are the chemicals that transmit signals between neurons in the brain. Research has shown that magnesium supplementation can support cognitive function and reduce the risk of cognitive decline in older adults (5).

One study found that older adults who took magnesium supplements for six months had strong cognitive function and memory compared to those who did not take magnesium (6). This suggests that magnesium may be an important nutrient for maintaining cognitive health and reducing the risk of age-related cognitive decline.

Finally, Magnesium has been shown to reduce levels of blood markers such as CRP (C-reactive protein) and IL-6 (interleukin-6) (7). This suggests that magnesium may be an important nutrient for reducing the risk of age-related decline.

In conclusion, magnesium is an important nutrient with many anti-aging properties. It has antioxidant system-supporting properties that help to reduce oxidative stress and protect cells from reactive oxygen species, support energy production and muscle function, maintain bone health, support cognitive function, and has other properties that help to reduce the risk of aging. While it is possible to get your magnesium from a healthy and careful diet, supplementation might be a good option.

References

Barbagallo M, Dominguez LJ. Magnesium and aging. Curr Pharm Des. 2010;16(7):832-9. doi: 10.2174/138161210790883463. PMID: 20166926.
Veronese N, Berton L, Carraro S, Bolzetta F, De Rui M, Perissinotto E, Toffanello ED, Bano G, Pizzato S, Miotto F, Coin A, Manzato E, Sergi G. Effect of oral magnesium supplementation on physical performance in healthy elderly women involved in a weekly exercise program: a randomized controlled trial. Am J Clin Nutr. 2014 Jul;100(1):974-81. doi: 10.3945/ajcn.113.080168. Epub 2014 May 7. PMID: 24808490.
Dominguez LJ, Barbagallo M, Lauretani F, Bandinelli S, Bos A, Corsi AM, Simonsick EM, Ferrucci L. Magnesium and muscle performance in older persons: the InCHIANTI study. Am J Clin Nutr. 2006 Aug;84(2):419-26. doi: 10.1093/ajcn/84.2.419. PMID: 16895891.
Castiglioni S, Cazzaniga A, Albisetti W, Maier JA. Magnesium and osteoporosis: current state of knowledge and future research directions. Nutrients. 2013 Jul 23;5(8):3022-33. doi: 10.3390/nu5083022. PMID: 23887789; PMCID: PMC3775240.
Boyle NB, Lawton C, Dye L. The effects of magnesium supplementation on subjective anxiety and stress-a systematic review. Nutrients. 2017 Apr 26;9(5):429. doi: 10.3390/nu9050429. PMID: 28445426; PMCID: PMC5452159.
Varner MW, Elbert JL, Hesse JL. The effect of magnesium on memory in the elderly. Neuropharmacology. 1981 Aug;20(8):835-9. doi: 10.1016/0028-3908(81)90080-6. PMID: 7317829.
Nielsen FH. Magnesium deficiency and increased inflammation: current perspectives. J Inflamm Res. 2018;11:25-34. Published 2018 Jan 18. doi: 10.2147/JIR.S136742. PMID: 29403375; PMCID: PMC5793269.

Glutathione and Brain Health: Protecting Against Oxidative Damage

emekblair1stg on May 15, 2023

Glutathione (GSH) is an essential component of the antioxidant system in the brain. It is a tripeptide composed of glutamate, cysteine, and glycine, and functions as a cofactor for various enzymes involved in detoxification, redox regulation, and protein folding. The brain has a high demand for GSH due to its high metabolic activity and vulnerability to oxidative stress, which can lead to neurodegeneration and cognitive decline. In this blog post, we will explore how the brain uses glutathione to protect itself from oxidative damage and maintain its function.

GSH synthesis and metabolism in the brain

The brain has the capacity to synthesize GSH de novo from the precursors cysteine, glutamate, and glycine, as well as recycle GSH through the glutathione reductase (GR) and glutathione peroxidase (GPx) systems. The rate-limiting step in GSH synthesis is the availability of cysteine, which is transported into the brain from the blood via the cystine/glutamate antiporter system xc-. This system is highly expressed in astrocytes, the main GSH synthesizing cells in the brain, and is regulated by various factors, including oxidative stress and inflammatory cytokines

Once synthesized, GSH can be metabolized by various enzymes, including glutathione S-transferases (GSTs), which conjugate GSH with xenobiotics and endogenous electrophiles for elimination, and gamma-glutamyl transpeptidase (GGT), which cleaves GSH into its constituent amino acids and generates extracellular glutamate, a major neurotransmitter in the brain. GSH can also be oxidized to its disulfide form (GSSG) by reactive oxygen species (ROS) and other electrophiles, which can be reduced back to GSH by GR using NADPH as a reducing agent.

GSH as part of the antioxidant system in the brain

One of the major functions of GSH in the brain is its role as part of the antioxidant system. The brain is particularly susceptible to oxidative stress due to its high oxygen consumption, lipid content, and relatively low levels of antioxidant enzymes compared to other tissues. The antioxidant system in the brain consists of several enzymes and molecules, including superoxide dismutase, catalase, GPx, and GSH. These components work together to neutralize ROS and RNS, donating electrons to neutralize these species and preventing their propagation. GSH acts as a direct scavenger of ROS and RNS and as a cofactor for GPx, which catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. GPx is highly expressed in neurons and astrocytes and is critical for protecting the brain against oxidative damage.

GSH as a redox regulator in the brain

In addition to its role in the antioxidant system, GSH also plays a critical role in regulating cellular redox status. GSH levels and the GSH/GSSG ratio are important indicators of oxidative stress and redox balance, with decreased GSH levels and increased GSSG levels being associated with neurological aging. GSH can modulate the activity of various redox-sensitive signaling pathways, including the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which regulates the expression of antioxidant and detoxification genes, and the mitogen-activated protein kinase (MAPK) pathway, which regulates cell proliferation, differentiation, and apoptosis. GSH can also modulate the activity of ion channels, transporters, and enzymes, including glutamate transporters, voltage-gated ion channels, and nitric oxide synthase, through redox-sensitive mechanisms.

Life implications

Given its critical role in protecting the brain against oxidative stress and regulating redox balance, alterations in GSH metabolism and function have been implicated in various neurological aging issues [5]. Decreased GSH levels and impaired GSH synthesis and recycling have been observed in aging, suggesting a potential therapeutic target for restoring redox balance and mitigating oxidative damage. Indeed, several studies have investigated the use of GSH precursors and GSH-enhancing agents, such as N-acetylcysteine and alpha-lipoic acid, in the treatment of neural aging.

In summary, glutathione is an essential component of the antioxidant system in the brain, acting as a direct scavenger of ROS and RNS and as a cofactor for GPx. It also plays a critical role in regulating redox balance and modulating cellular signaling pathways. Alterations in GSH metabolism and function have been implicated in various neurological aging while restoring redox balance and mitigating oxidative damage. Further research is needed to elucidate the precise mechanisms by which GSH protects the brain and encourage effective GSH-based supplementation.

References

Dringen R. Metabolism and functions of glutathione in brain. Prog Neurobiol. 2000;62(6):649-671. doi:10.1016/s0301-0082(99)00060-x
Dringen R, Gutterer JM, Hirrlinger J. Glutathione metabolism in brain: metabolic interaction between astrocytes and neurons in the defense against oxidative stress. Eur J Biochem. 2000;267(16):4912-4916. doi:10.1046/j.1432-1327.2000.01599.x
Dringen R. Glutathione peroxidase and redox-regulation of neuronal cell death. Neurochem Int. 2000;37(2-3):133-142. doi:10.1016/s0197-0186(00)00012-4
Franco R, Cidlowski JA. Apoptosis and glutathione: beyond an antioxidant. Cell Death Differ. 2009;16(10):1303-1314. doi:10.1038/cdd.2009.107
Sian J, Dexter DT, Lees AJ, et al. Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol. 1994;36(3):348-355. doi:10.1002/ana.410360305
Pocernich CB, Butterfield DA. Elevation of glutathione as a therapeutic strategy in Alzheimer disease. Biochim Biophys Acta. 2012;1822(5):625-630. doi:10.1016/j.bbadis.2011.10.005

Glutathione and its Role in Regulating Redox Balance in the Brain

emekblair1stg on May 15, 2023

How Glutathione (GSH) Regulates Redox Balance in the Brain

Glutathione (GSH) is a tripeptide molecule composed of cysteine, glutamate, and glycine that plays a critical role in regulating redox balance in the brain. As part of the antioxidant system, GSH acts as a direct scavenger of reactive oxygen species (ROS) and reactive nitrogen species (RNS). It also functions as a cofactor for glutathione peroxidase (GPx), an enzyme that catalyzes the reduction of hydrogen peroxide and lipid peroxides to their corresponding alcohols. Through these mechanisms, GSH helps to prevent oxidative damage to proteins, lipids, and DNA in neurons, which can lead to cell death.

The Role of Other Redox-Active Molecules in GSH Metabolism and Function in the Brain

GSH metabolism and function are closely intertwined with those of other redox-active molecules, such as glutathione reductase (GR), glutathione S-transferase (GST), and thioredoxin reductase (TR), which collectively help to maintain redox homeostasis in the brain. GSH synthesis and recycling are regulated by a variety of factors, including oxidative stress, cytokines, and growth factors, which can modulate the expression and activity of key enzymes involved in GSH metabolism, such as gamma-glutamylcysteine synthetase (γ-GCS) and glutathione peroxidase 4 (GPx4).

The Role of Astrocytes in GSH Production and Transport to Neurons, and the Effect of GSH on Cellular Signaling Pathways and Components in the Brain

Astrocytes are major producers of GSH, and they transport GSH to neurons via specific transporters, such as the excitatory amino acid transporter 2 (EAAT2) and the system xc- cystine/glutamate antiporter. GSH has also been shown to modulate cellular signaling pathways, including the activation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-κB (NF-κB) transcription factor, as well as the inhibition of apoptosis through the regulation of caspase activity. GSH interacts with a variety of other cellular components, such as ion channels and nitric oxide synthase, through redox-sensitive mechanisms.

The Potential Role of GSH-Based Therapies in Preventing Neurodegeneration and Restoring Redox Balance in the Brain

GSH has been implicated in the prevention of neurodegeneration and oxidative damage in the brain. Decreased GSH levels and impaired GSH synthesis and recycling have been observed in various neurological conditions. Thus, GSH-based therapies have been suggested as a potential therapeutic target for restoring redox balance and mitigating oxidative damage in the brain.

In conclusion, glutathione is a crucial component of the antioxidant system in the brain, acting as a direct scavenger of ROS and RNS and as a cofactor for GPx. It also plays a vital role in regulating redox balance and modulating cellular signaling pathways. Alterations in GSH metabolism and function have been implicated in various neurological conditions, suggesting a potential therapeutic target for restoring redox balance and mitigating oxidative damage in the brain.

References

Dringen R. Metabolism and functions of glutathione in brain. Prog Neurobiol. 2000 Apr;62(6):649-71. doi: 10.1016/s0301-0082(99)00060-x. PMID: 10788757.

Sato H, Tamba M, Okuno S, Sato K, Keino-Masu K, Masu M, Bannai S. Distribution of cystine/glutamate exchange transporter, system xc-, in the mouse brain. J Neurosci. 2002 Mar 15;22(6):8028-33. doi: 10.1523/JNEUROSCI.22-18-08028.2002. PMID: 12223547.

Fraternale A, Paoletti MF, Casabianca A, Nencioni L, Gatta V, Brundu S, Garaci E, Ciriolo MR. GSH and analogs in antiviral therapy. Mol Aspects Med. 2009 Apr-Jun;30(2-3):99-110. doi: 10.1016/j.mam.2009.04.001. Epub 2009 Apr 12. PMID: 19362157.

Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004 Mar;134(3):489-92. doi: 10.1093/jn/134.3.489. PMID: 14988435.

Hohnholt MC, Dringen R. Effects of glutathione depletion and inhibition of glutathione synthesis on the hypotaurine- and taurine-modulated release of dopamine from cultured PC12 cells. J Neurochem. 2013 Sep;126(6):746-56. doi: 10.1111/jnc.12334. Epub 2013 Jun 20. PMID: 23692920.

Lushchak VI. Glutathione homeostasis and functions: potential targets for medical interventions. J Amino Acids. 2012;2012:736837. doi: 10.1155/2012/736837. Epub 2012 Oct 16. PMID: 23125505.

Zeevalk GD, Bernard LP, Guilford FT. Lipopolysaccharide increases glutathione uptake and glutathione levels in cultured astrocytes. J Neurochem. 1998 Jul;71(1):429-34. doi: 10.1046/j.1471-4159.1998.71010429.x. PMID: 9648863.

Sies H. Glutathione and its role in cellular functions. Free Radic Biol Med. 1999 Nov;27(9-10):916-21. doi: 10.1016/s0891-5849(99)00177-x. PMID: 10569624.

The Dangers of a High Sugar Diet

emekblair1stg on May 15, 2023

Sugar is a type of carbohydrate that can be found naturally in fruits, vegetables, and milk, as well as in processed foods such as candy, soft drinks, and baked goods. While our bodies need sugar to function, consuming too much of it can have negative effects on our health.

Key Highlights

Weight Gain: Consuming too much sugar can lead to weight gain over time, as excess sugar is converted into fat and accumulates in the body.
Health Risks: A high sugar diet can lead to the development of visceral fat, which has been linked to an increased risk of heart disease, high blood pressure, and other health problems.
Insulin Resistance and Mental Health: Consuming too much sugar can also lead to insulin resistance, which can cause our bodies to store more fat and further contribute to weight gain. Additionally, studies have shown that consuming too much sugar can have negative effects on our mental health, leading to feelings of anxiety, depression, and mood swings.

The Link Between High Sugar Diet and Weight Gain

One of the main concerns with a high sugar diet is weight gain. When we consume sugar, it quickly broken down into glucose and fructose in our bodies. While glucose can be metabolized by most tissues, fructose can only be metabolized by the liver. When the liver is overloaded with fructose, it converts it into fat in a process called de novo lipogenesis. This excess fat can accumulate in our bodies, leading to weight gain over time.

The Health Risks of High Sugar Diets

Moreover, consuming too much sugar can lead to the development of visceral fat, which is the fat that accumulates around our internal organs. Visceral fat has been linked to an increased risk of heart disease, high blood pressure, and other health problems.

In addition to contributing to weight gain, a high sugar diet can also lead to insulin resistance. Insulin is a hormone that regulates blood sugar levels in our bodies. When we consume too much sugar, our bodies release more insulin to compensate. Over time, this can lead to insulin resistance, a condition where our bodies are no longer able to respond properly to insulin. Insulin resistance can cause our bodies to store more fat, which can further contribute to weight gain.

Finally, a high sugar diet can also have negative effects on our mental health. Studies have shown that consuming too much sugar can lead to feelings of anxiety, depression, and mood swings.

In conclusion, while sugar is a necessary part of our diets, consuming too much of it can lead to weight gain, the development of visceral fat, insulin resistance, and negative effects on our mental health. It is important to be mindful of our sugar intake and to consume it in moderation.

References:

Stanhope, K. L. (2016). Sugar consumption, metabolic disease, and obesity: The state of the controversy. Critical reviews in clinical laboratory sciences, 53(1), 52-67.

Neeland, I. J., Poirier, P., & Després, J. P. (2018). Cardiovascular and metabolic heterogeneity of obesity: Clinical challenges and implications for management. Circulation, 137(13), 1391-1406.

Stanhope, K. L. (2012). Role of fructose-containing sugars in the epidemics of obesity and metabolic syndrome. Annual review of medicine, 63, 329-343.

Westover, A. N., Marangell, L. B. (2002). A cross-national relationship between sugar consumption and major depression? Depression and Anxiety, 16(3), 118–120.