Would you like to slow the hands of time and preserve your brain health well into old age? Glutathione is a superstar nutrient, made naturally by your body, and known as both the “Master Antioxidant” and the “Heavy Metal Chelator.” Glutathione counteracts the everyday wear and tear on your brain, called oxidation. Its far-reaching benefits don’t stop there. It can help keep skin radiant and wrinkle-free, it is critical for healthy cells, and a longer lifespan, and it helps your liver detoxify a long list of chemicals, including alcohol and mercury. If your cells are healthy, they are likely chock full of glutathione. But if you are struggling with illness, chances are good your glutathione reserves are in the tank.1 We focus on the benefits of glutathione for a strong, capable brain in this blog. Scientists are busy investigating glutathione for its powerful role in maintaining and protecting a healthy brain, even against conditions such as Parkinson’s and Alzheimer’s. If you are aging, getting the usual daily toxic exposures, or don’t have fully functioning glutathione enzymes, your brain may be prone to toxin overload and more free radical damage. You may notice your mind slipping, your memory failing, or changes in your mood. Clinicians and consumers, keep reading to learn the power of glutathione for preserving brain function. Scroll to the end to find out the genetic and nutritional testing that will tell you if you need more glutathione and how to boost glutathione with food and supplements.
We are grateful to our sponsor, DaVinci Laboratories, for making this blog possible.
Oxygen is necessary for life, but it also can be our undoing.
Our cells sustain normal wear and tear day after day. Mitochondria, or the powerhouses of our cells, chug away all day keeping our bodies running strong. But the side effect is harmful oxygen molecules called reactive oxygen species. Much like exhaust coming from your car’s engine, free radicals are the unhealthy waste products that come from our cells. That’s why every cell is equipped with loads of glutathione and other antioxidants- to make those free radicals harmless so we can keep on keeping on.
Normal amounts of free radicals are healthy. As long as our antioxidant systems are in good shape, free radicals are kept in check, and they can’t do damage. However, if free radicals build up too much, they can cause damage. This is known as oxidative stress. Oxygen free radicals can be very damaging to DNA, mitochondria, proteins, cells, tissues, and organs. Oxidative stress is a driving factor of the aging process. One of the main areas where oxidative stress takes a toll is the brain and nervous system.2 It can also do a number on heart health, the lungs, blood sugar handling, and the kidneys.1,3,4
Free Radicals Wreck the Brain
Oxidative stress is terrible for the brain, even though the brain thrives on oxygen. The brain represents only about 2% of body weight, but it consumes 20% of your daily oxygen!5 Oxidative stress is a main way that we lose brain cells as we age.3,4 It’s to blame for our worsening cognitive function as we grow older and has been documented in numerous studies.6
Oxidative stress is believed to be a major underlying mechanism of neurodegenerative conditions, especially those known to have mitochondrial defects, such as Parkinson’s, Huntington’s, and Alzheimer’s diseases. Diseases that involve the slow and progressive loss of neurons in the brain and spine are called neurodegenerative diseases.4 People with these conditions are also more likely to have high levels of lipid peroxides and damage to DNA and proteins, which further suggests oxidative stress is a factor in the brain and nervous system downward spiral.5 Brain function can improve when taking antioxidant supplements or eating antioxidant foods, though not all studies agree on this.4
There are a few reasons why the brain is a prime target for damage from free radicals. First of all, it processes a lot of oxygen. Second, it is full of fats (or lipids), which are prone to free radical damage. Think of fat going rancid. Or better yet, think of fish oil going rancid. That’s your brain on oxidative stress. The brain is also rich in iron and copper, which can contribute to oxidative stress. Lastly, scientists have found that there just isn’t enough naturally occurring glutathione (the brain’s major antioxidant) in the brain to counteract the constant stream of oxidative stress.4
You Might Have Low Glutathione Levels if You:
- Are getting older
- Drink alcohol
- Have mercury amalgams or eat tuna fish every week
- Take medications
- Eat conventional vegetables (grown with pesticides or POPs)
- Don’t eat colorful and cruciferous vegetables regularly
- Eat a low-protein diet
- Feel inflamed
- Do not recover from injuries easily
- Have one or more chronic illnesses
- Have brain or spinal cord problems
- Have trouble sleeping
- Feel stressed
- Move with difficulty; have trouble controlling body movements
- Feel low or blue
- Experience nervousness
- Struggle with restlessness
What is Glutathione?
Glutathione (GSH) is a tripeptide, meaning it’s made up of three amino acids: cysteine, glutamic acid, and glycine. Your body naturally makes lots of glutathione every day, as long as all of the building blocks are available. Your body makes glutathione from amino acids in the protein you eat. Levels in healthy cells are quite high (in the same ballpark as glucose and cholesterol).1 Glutathione is such a powerful, important, and broad-acting antioxidant, it is famously called the “Master Antioxidant.” It also acts as a heavy metal chelator and is critical for both major phases of liver detoxification.
Glutathione: Key to A Healthy Aging Brain
Glutathione puts the kibosh on oxidative stress. It turns bad free radical molecules into harmless molecules. It does this for many, many free radicals- not just a few. Glutathione can turn singlet oxygen, hydroxyl radicals, and superoxide radicals into harmless chemicals. It scavenges nitric oxide and carbon radicals. It helps to detoxify hydroperoxides, peroxynitrites, and lipid peroxides.1 It also fights against free radicals that are made in the process of getting toxins ready to leave the body (known as Phase I liver metabolism). Glutathione takes mercury out of cells and out of the brain.1 It neutralizes persistent organic pollutants and many oxidative chemicals.
This superstar nutrient doesn’t just get rid of bad free radicals, it boosts other antioxidants. Glutathione helps to generate the antioxidant vitamins C and E. It also helps a number of antioxidant enzymes work properly.
Conditions affecting the brain and nervous system often show low glutathione levels.1 When people have genetic defects in glutathione metabolism, there is always a poor outcome for the brain and nervous system. That leads scientists to believe glutathione is fundamental for brain health.5
Glutathione has two forms. One is reduced glutathione, the antioxidant form that picks up and neutralizes free radicals. The other form is oxidized glutathione. This is the “used up” form of glutathione that cannot do good until it gets recycled into its reduced glutathione form again. When buying glutathione supplements, it’s the reduced glutathione that you want.
“Perhaps the best indicator of the importance of glutathione is that its cellular and mitochondrial levels directly are highly associated with health and longevity.”1 -J. Pizzorno
Glutathione Powers Up the Brain
Glutathione is vital for healthy mitochondria. Remember how we discussed the mitochondria of the cells? These powerhouses make a lot of energy- and a lot of toxic free radical waste. Mitochondria are critical for your brain to function. When they break down, brain aging occurs.6 The more mitochondria, the better memory, cognitive function, and word recall you will have. Your brain cells have to produce a lot of energy to keep going and going. Glutathione helps keep mitochondrial DNA in good shape.1 By taking glutathione, you are helping boost your brain cells’ energy and get rid of the toxic oxidative waste that they produce. That’s a win-win!
What Do Your Glutathione Genes Say About Your Brain Health?
Glutathione enzymes help glutathione do its work in the body to keep you healthy. You may remember that enzymes catalyze chemical reactions. They are like little single-unit factories in the cell.
Glutathione-S-transferase (GST) is a glutathione enzyme that helps the body get rid of many environmental toxins, including solvents, herbicides, fungicides, lipid peroxides, and heavy metals (e.g., mercury, cadmium, and lead). The various forms of GST work together to eliminate toxins.
However, some people have weak glutathione enzymes- or none at all- because the DNA for those enzymes is mutated. They may have a SNP or single nucleotide polymorphism, meaning a very small change to a genetic code. These genetic mutations are common and you might never know that you have one unless you get tested. If your glutathione conjugation enzymes aren’t able to work well, toxins and oxidative stress can build up in your body.
GST is an example of this. GSTM1 is mutated in 75% of Caucasians and 25% of Africans. It can also be completely absent. When this enzyme doesn’t work at top capacity, it can cause problems for the brain.7 Mutations in your glutathione enzymes such as GST have been associated with more abnormal, unhealthy cells.8,9 That’s because if you don’t have good glutathione enzymes, toxins and oxidative stress build up. These bad players can damage cells, which can eventually become harmful rogue cells. However, supplements and diet can help. Even with the GSTM1 gene mutation, if you eat cruciferous vegetables four times per week, you can increase your glutathione levels by 16 – 38%.10
An Integrative and Functional Medicine Approach to Brain Health
Integrative and functional medicine practitioners often support brain health by trying to turn off oxidative stress and swing the balance more toward antioxidants in the brain. They may also look for underlying sources of oxidative stress and inflammation, which often go together. They will investigate signs of toxicity or problems with detoxification. Hormone imbalances could lead to both problems with liver detoxification and oxidative stress. As I explained in the blog, “How to Find a Good Integrative and Functional Medicine Doctor” this root cause approach is different than conventional medicine. Instead of labeling the disease and treating the symptoms, the integrative and functional medicine approach looks for underlying causes that could be out of balance and addresses them. By balancing a person’s oxidative stress burden with diet and lifestyle, they can improve movement, preserve brain cells, slow brain aging, and give relief to people with mood issues.
Are You Getting Enough Glutathione-Rich Foods?
Low glutathione levels mean the brain is left wide open to the daily buildup of toxic waste products. Since glutathione is made of amino acids, protein is an important precursor for making glutathione. The glutathione amino acid precursors are glutamic acid, glycine, and cysteine. The amino acid glutamine is a sister to glutamic acid, which might explain why having good glutamine levels can also help boost glutathione.
Glutathione contains sulfur amino acids. Think of the smell of broccoli or eggs- that’s sulfur. Foods high in sulfur ramp up glutathione production in the body. Examples are cruciferous vegetables like broccoli, cauliflower, and Brussels sprouts. You may have low glutathione levels if you are eating a standard American diet, low in these vegetables. Other sulfur-containing foods that boost glutathione include eggs, nuts, garlic and onions, and lean protein like fish and chicken.
Foods That Help Build Your Glutathione Levels:
Glutamine- beef, pork, chicken, dairy products, spinach, parsley, and cabbage
Glycine- turkey, pork, chicken, soybean, seaweed, eggs, and amaranth
Methionine- turkey, pork, chicken, beef, eggs, Brazil nuts, soybeans, and sesame seeds
Even though glutathione is made naturally by the body, it can also be taken as a supplement (pill, liquid), given as an intravenous (IV) therapy, or injected. Historically, glutathione supplements were hard to get into the body. Glutathione is easily broken down in the gastrointestinal tract and liver and only small quantities reach circulation. Also, glutathione can’t be stored easily. Exposing it to heat and light weakens its antioxidant activity. There also is ongoing debate as to whether glutathione supplements are even absorbed, since taking them doesn’t reliably increase blood levels.
Most integrative and functional medicine doctors are aware that glutathione oral supplementation has challenges. Clinicians often opt for glutathione supplements that are easier for the body to use, such as DaVinci Laboratories’ Glutathione with Provail. It is 2.5 times better absorbed than the leading glutathione supplements on the market and is backed by a published study. It increases glutathione in blood and tissues as well as boosts antioxidant activity. Clinicians and consumers can also boost levels of glutathione in their patients by having them take glutathione precursors like the amino acid, N-acetyl L-cysteine (NAC). Liposomal supplements containing reduced glutathione are also popular.
Dosages of glutathione supplements range from 250 – 450 mg, once to three times daily. Because glutathione is already found throughout your body, there is no toxic dose, but going over 2,000 mg per day should only be done with the oversight of a knowledgeable integrative and functional medicine provider. Another reason to work with a practitioner is that glutathione can speed detoxification, which isn’t always a good thing, especially for people who are particularly weak or compromised.
If you are interested in liver detoxification, see my earlier blog, “Naturally Detox Everyday With These Foods and Supplements.”
There are many tests to help figure out if you are struggling with too many free radicals and/or low glutathione. Perhaps the most important is to see if you have oxidative stress, which would be an indirect clue that you could benefit from glutathione. We can test for how much glutathione is in your blood. Another way is to test for the amino acids that make up glutathione. That tells you if you have enough of your glutathione building blocks. There are also functional markers of glutathione need, such as organic acids, which we won’t dive into here. Genetic tests can tell you about your glutathione enzymes, like GST, and if they work well.
Blood glutathione– measures glutathione levels directly in blood.
8-hydroxy-2-deoxyguanosine– urine marker of DNA damage and oxidative stress.
Lipid peroxides– urine marker of oxidized lipids.
Amino acids– comes as a blood or urine test; measures the precursor amino acids for making glutathione (glycine, cysteine (methionine), glutamic acid, and glutamine).
Genomics test for glutathione-S-transferase and other glutathione enzymes– cheek swab test that tells you about your genes involved in glutathione detoxification.
Glutathione May Be the Most Important Supplement for Your Brain
Glutathione is fundamental for brain health. The brain is a high-energy organ and consumes huge quantities of oxygen. But the side effect of all this metabolism is a massive burden of free radicals, which ironically can harm the brain. In healthy people, oxidative stress is kept under control with the help of antioxidants like glutathione, glutathione enzymes, and other antioxidant vitamins and minerals. However, due to diet, stress, medication, toxic exposures, or weakened glutathione enzymes, a person’s free radicals and toxins can build up. This state of oxidative stress can wreak havoc on the brain, speeding up aging and unraveling the nervous system. Clinicians and consumers can test a person’s levels of oxidative stress, their glutathione levels, or their glutathione enzyme genes. With testing, diet, and supplements, you can boost glutathione levels and maintain a healthy balance of free radicals. You will think better, remember more, and ward off brain aging when you combat oxidative stress by building up your glutathione stores.
Take These Steps to Nourish and Protect Brain Cells
- Eat foods that build glutathione: broccoli, collard greens, Brussels sprouts, kale, onions, and garlic.
- Eat healthy levels of protein (20-30% of your daily calories or a customized recommendation from your nutrition practitioner).
- Increase glutathione blood levels with glutathione supplements, such as DaVinci Laboratories’ Glutathione with Provail®.
- Test for oxidative stress markers, such as 8-hydroxy-2-deoxyguanosine or lipid peroxides.
- Test for glutathione status and amino acid precursors.
- Test for genetic glutathione enzyme status, such as the Detoxigenomics test from Genova Diagnostics.
- Avoid toxins that deplete your glutathione such as mercury, cadmium, alcohol, smoke, charred foods, pesticides, and solvents.
- Take other supportive antioxidants such as selenium, vitamin C, vitamin E, and lipoic acid.
Since 1973, DaVinci® Laboratories has been a leader in nutritional research, product development, and innovation. Our dedication to higher integrity and insistence on superior quality are reflections of our core values. Our team of experts is always willing to assist you in matters relating to nutrition. Today, DaVinci® continues to set new standards for quality and product innovation to keep you as healthy and informed as possible.
- Pizzorno J. Glutathione! Integr Med (Encinitas). Feb 2014;13(1):8-12.
- Pizzino G, Irrera N, Cucinotta M, et al. Oxidative Stress: Harms and Benefits for Human Health. Oxidative medicine and cellular longevity. 2017;2017:8416763. doi:10.1155/2017/8416763
- Jomova K, Raptova R, Alomar SY, et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol. Oct 2023;97(10):2499-2574. doi:10.1007/s00204-023-03562-9
- Kim GH, Kim JE, Rhie SJ, Yoon S. The Role of Oxidative Stress in Neurodegenerative Diseases. Exp Neurobiol. Dec 2015;24(4):325-40. doi:10.5607/en.2015.24.4.325
- Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL. Glutathione dysregulation and the etiology and progression of human diseases. Biological chemistry. Mar 2009;390(3):191-214. doi:10.1515/BC.2009.033
- Kandlur A, Satyamoorthy K, Gangadharan G. Oxidative Stress in Cognitive and Epigenetic Aging: A Retrospective Glance. Front Mol Neurosci. 2020;13:41. doi:10.3389/fnmol.2020.00041
- Jafarian Z, Saliminejad K, Kamali K, et al. Association of glutathione S-transferases M1, P1 and T1 variations and risk of late-onset Alzheimer’s disease. Neurol Res. Jan 2018;40(1):41-44. doi:10.1080/01616412.2017.1390902
- Li S, Xue F, Zheng Y, et al. GSTM1 and GSTT1 null genotype increase the risk of hepatocellular carcinoma: evidence based on 46 studies. Cancer Cell Int. 2019;19:76. doi:10.1186/s12935-019-0792-3
- Nakanishi G, Pita-Oliveira M, Bertagnolli LS, et al. Worldwide Systematic Review of GSTM1 and GSTT1 Null Genotypes by Continent, Ethnicity, and Therapeutic Area. OMICS. Oct 2022;26(10):528-541. doi:10.1089/omi.2022.0090
- Pizzorno J, Murray M, eds. Textbook of Natural Medicine. 5th ed. Elsevier; 2021.
Cass Nelson-Dooley, MS, is a researcher, author, educator, and laboratory consultant. She studied medicinal plants in the rain forests of Panama as a Fulbright Scholar and then launched a career in science and natural medicine. Early on, she studied ethnobotany, ethnopharmacology, and drug discovery at the University of Georgia and AptoTec, Inc. She joined innovators at Metametrix Clinical Laboratory as a medical education consultant helping clinicians use integrative and functional laboratory results in clinical practice. She owns Health First Consulting, LLC, a medical communications company with the mission to improve human health using the written word. Ms. Nelson-Dooley is an oral microbiome expert and author of Heal Your Oral Microbiome. She was a contributing author in Laboratory Evaluations for Integrative and Functional Medicine and Case Studies in Integrative and Functional Medicine. She has published case studies, book chapters, and journal articles about the oral microbiome, natural medicine, nutrition, laboratory testing, obesity, and osteoporosis.