Feeling Tired and Fatigued? Boost Energy by Supporting Mitochondria

Feeling fatigued? Feeling exhausted by your gym workouts? Are normal daily tasks taking it out of you when they didn’t before? Some people will reach for coffee or a sugary snack to boost their energy levels. But the real reason for your flagging energy levels is hidden within your cells. Stationed in every cell of the body, mitochondria are the powerhouses of our cells. They are little generators, powering the actions of our cells, day in and day out. And the energy currency that they are so keen on making? ATP or adenosine triphosphate. So, when our energy levels are hitting rock bottom, we should check on our mitochondrial health right away. In this article, we will discuss fatigue and mitochondria, how to support energy levels with nutritional supplements, and the tests that will help you figure out if weakened mitochondria are the reason your energy is plummeting.

In integrative and functional medicine, we want to optimize mitochondrial health. One reason is so that people have plenty of energy, yes. High-performance athletes do well when supporting mitochondria. But there are many other reasons, too. Good mitochondrial function promotes a sharp brain, metabolism, heart health, liver health, it is linked to a longer lifespan, and more. That’s because when cells are fueled up with lots of energy, they perform at their best.

We are grateful to our sponsor, DaVinci Laboratories, for making this blog possible. 

 

How Oxidative Stress Harms Your Health

Mitochondria chug away all day keeping our bodies running strong. But there is a dangerous side effect: 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 going and going. We will talk about how glutathione is one powerful antidote to oxidative stress, so keep reading.

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 don’t do damage. However, if free radicals build up too much, they can bump around, damaging everything in their path. This is known as oxidative stress. Oxygen free radicals are very harmful to DNA, mitochondria, proteins, cells, tissues, and organs.

Oxidative stress causes us to grow old. Oxidative stress hurts the mitochondria, which cripples energy production throughout the body. That’s not all. Oxidative stress takes a toll on the brain and nervous system.¹ It can also interfere with heart health, the lungs, blood sugar handling, and the kidneys.^2-4

 

Glutathione Wards Off Oxidative Stress

Glutathione (GSH for short) is a tiny protein made from three amino acids: cysteine, glutamic acid, and glycine. Your body naturally puts these building blocks together from the protein you eat. Because it works in so many different ways to protect your cells, people often call it the “Master Antioxidant.” It not only fights off free radicals, but also helps your liver clear out toxins and even binds to heavy metals so your body can get rid of them.

When there is plenty of glutathione, then the mitochondria are likely in good shape. When glutathione is low, it is a sign that mitochondria are stressed and creating so much oxidative damage that they are burning up the cell’s glutathione reserves.

You and your integrative and functional medicine practitioner can build your body’s levels of glutathione using diet, supplements (like pills or liquids), an IV treatment, or even an injection. We review this later in the section, “Boost Energy Levels with Antioxidants and Mitochondrial Support.”

 

Chronic Fatigue is A Problem of Mitochondria and Oxidative Stress

Oxidative stress plays a clear role in chronic fatigue syndrome (or myalgic encephalomyelitis), which is characterized by profound fatigue that lasts more than 6 months, fatigue with exercise, tiredness even after sleep, and trouble thinking clearly or even maintaining blood pressure upon standing. Many studies highlight the role of mitochondrial dysfunction and oxidative stress in patients with chronic fatigue. People complaining of chronic fatigue syndrome have more oxidative stress than controls. And the higher their markers of oxidative stress, the more likely they are to be severely fatigued, have muscle pain, and cognitive issues.^5-7

 

Glutathione Supports Mitochondria and Combats Fatigue

Some studies have shown that people with fatigue have lower levels of glutathione in blood or other tissues⁸ and more oxidative stress.⁹ Lower glutathione has been detected in chronic fatigue patients.¹⁰ When animals wear down under physical exertion (like trying to keep swimming for long periods of time), high oxidative stress and low glutathione are at the root cause.¹¹

When glutathione or its precursors are supplemented, it can combat fatigue and boost muscle function under demanding athletic conditions in both humans and mice.¹² Taking glutathione reduces oxidative stress.^13,14 Building up glutathione promotes healthy mitochondrial function and improves cognition. When healthy young men were given precursors of glutathione, they were less fatigued during endurance exercise.¹⁵

Treatments for mitochondrial diseases even call for giving N-acetylcysteine, a precursor to glutathione. NAC helps to restore glutathione balance, calm down oxidative stress, improve mitochondrial function, and promote healthier neuromuscular activity in people with mitochondrial disease. Other mitochondria support supplements include  CoQ10, B vitamins, carnitine, and/or minerals.¹⁶ All of these nutrients work hand in hand to help mitochondria function at their best for energy, heart, and brain health.

Not all studies agree and there is still much more to learn. Luckily, more research is currently underway, such as one trial by Purdue University’s College of Pharmacy called “Assessment of N-Acetylcysteine as Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome,” which is testing NAC  at different doses and measuring brain glutathione and oxidative stress markers.

 

What Causes Mitochondria to Stop Working?

Mitochondria can stop performing for a few reasons. Genetic causes can disable an important enzyme required for mitochondrial function. An infection can harm the mitochondria. We often see this when a person has an infection and can’t seem to ever get well again; they are often troubled with chronic fatigue. Long-haul COVID is one example. In fact, there are many similarities between chronic fatigue and Long COVID. Both of these conditions are treated with mitochondrial support supplements by integrative and functional medicine practitioners.¹⁷

As discussed earlier, a buildup of oxidative damage harms mitochondria. Mitochondria may stop working if there aren’t adequate vitamins and minerals needed to make ATP. Other things that can harm mitochondria and put the kibosh on energy production are: toxins like heavy metals, chronic stress, imbalanced blood sugar, or gut microbiome dysbiosis. There are tests and treatments for how well mitochondria are working, which I will expand on in this article.

 

Healthy Mitochondria Are Critical for Energy Levels, a Strong Heart, and a Sharp Mind

To illustrate how fundamental mitochondria are to our overall health, one need only look at mitochondrial diseases. These disorders can really muck up the works and make daily life super difficult. These are inherited, genetic conditions that interfere with mitochondrial energy production. People with a mitochondrial disease may be missing an enzyme that is critical for mitochondria to work. Mitochondrial diseases often show up as fatigue and weakness, but they can affect many organs in the body in different ways.

Symptoms of mitochondrial disease include:

• Fatigue
• Muscle weakness or pain
• Exercise intolerance

Other common symptoms are impaired vision, hearing loss, cognitive and developmental problems, irregular heartbeat, weak or enlarged heart muscle, diabetes, gastrointestinal symptoms, metabolic imbalances, and short stature.

It’s clear to see. When the mitochondria are damaged, the consequences are profound. While most people do not have these types of problems with their mitochondria, it is undeniable that mitochondria are essential for good health.

While most people don’t have true mitochondrial disease, they may have more subtle problems that point to problems with mitochondrial health. In integrative and functional medicine, this is often called mitochondrial dysfunction. It is just a malfunction or a suboptimum performance of mitochondria.¹⁸ Mitochondrial dysfunction has been associated with over 40 chronic health problems, including type 2 diabetes, cancer, Alzheimer’s, and other conditions of the nervous system. Persistent fatigue is a common complaint. Mitochondria may become run down due to aging, a buildup of oxidative stress, or even toxins, especially after years of accumulation in the body.  Symptoms aren’t as urgent or life-threatening as actual mitochondrial diseases, but they can make you chronically unhealthy, wearing away at your quality of life. Symptoms may stick around for years and most conventional doctors won’t be able to figure them out.

Symptoms of Mitochondrial Dysfunction:¹⁹

• Brain fog
• Cold intolerance
• Exercise intolerance
• Fatigue
• Headaches or migraines
• Heart palpitations or rapid heart rate with little exertion
• Muscle pain, weakness, or cramps
• Sleep problems
• Weight gain or difficulty losing weight
• Fatigue

 

Boost Energy Levels with Antioxidants and Mitochondrial Support

Clinicians and patients can help balance the scales of oxidative stress using food, antioxidant supplements, and by avoiding toxins. Colorful vegetables and fruits are high in antioxidants. Cruciferous vegetables help promote glutathione. Supplements such as quercetin and resveratrol can reduce oxidative stress. Nutrients to support mitochondrial function include coenzyme Q10, carnitine, lipoic acid, B vitamins, and minerals.

Your body naturally makes glutathione, but you can also get it as a pill, liquid, or IV drip. There are some concerns about how well glutathione absorbs and its stability. Because of these challenges, many integrative and functional medicine doctors choose forms of glutathione that your body can use more efficiently. One example is DaVinci Laboratories’ Glutathione with Provail, which has been shown in a published study to be about 2.5 times better absorbed than many standard glutathione supplements.¹³ It not only raises glutathione levels in blood and tissues but also boosts antioxidant activity. Another strategy doctors use is providing the precursors — nutrients like NAC that help your body build more glutathione on its own. Glutamine and other amino acids help to make glutathione. Liposomal glutathione (a special form wrapped in fat molecules) is also popular.

Typical supplement dosages run anywhere from 250 to 450 mg, taken once to three times daily. Since glutathione already exists in your body, it is safe, but taking more than 2,000 mg a day should only be done under the guidance of a skilled integrative or functional medicine practitioner.

Staying away from toxins in food, water, and air help to preserve antioxidants for the cell’s use, instead of adding a further toxic burden for the body to deal with.

 

The Best Tests for Glutathione and Oxidative Stress

There are several ways to find out if your body is under attack from too many free radicals or if your glutathione levels are running low. One of the biggest clues is looking for signs of oxidative stress, since that often means your body could use more antioxidant support like glutathione. Examples are 8-hydroxy-2-deoxyguanosine or lipid peroxides. Doctors can measure glutathione directly in your blood, or they can look at the amino acids that act as glutathione building blocks to see if you have enough raw material to keep production going. There are also functional tests, such as the Organic Acid Profile OAp from Diagnostic Solutions, which give clues about your body’s glutathione demand and mitochondrial function. On top of that, genetic testing can reveal whether your glutathione-related enzymes are working as they should. Find an integrative and functional medicine provider to help order and interpret these tests.

Tests for Fatigue and Mitochondrial Dysfunction:

• Organic acids (urine) are markers of blocked metabolic pathways
  • • Krebs cycle mitochondrial markers
    • L-Lactic acid
    • a-Hydroxybutyrate
    • Pyroglutamate
    • a-Ketobutyric acid
• Blood glutathione – measures glutathione levels directly in the blood.
• 8-hydroxy-2-deoxyguanosine – a urine marker that shows DNA damage and oxidative stress.
• Lipid peroxides – a urine test that reflects damage to fats in your body caused by oxidation.
• Amino acids – available as a blood or urine test; checks the glutathione building blocks glycine, cysteine (or methionine), glutamic acid, and glutamine.
• Genomic testing for glutathione-S-transferase and other enzymes – usually a cheek swab that looks at how well your glutathione detoxification genes are functioning.

Organic acid urine tests are excellent for learning about mitochondria, glutathione status, and oxidative stress levels. In fact, these urine markers are also used as part of newborn screening to detect mitochondrial diseases. There are a handful of markers in an organic acid urine profile that I specifically like for fatigue and mitochondrial dysfunction. Krebs cycle urine markers help to identify if energy production is failing. Urine lactic acid can also give clues to how well energy pathways are working. In addition, the OAp tests a person for how well they are synthesizing glutathione and if they are wasting it by accident. When I see test results showing ineffective mitochondria, desperate need for glutathione, and oxidative stress, patients usually feel awful. They need a good diet and nutrition protocol to get them feeling better again.

Promote Mitochondrial Health and Say Goodbye to Fatigue

If you’ve been dragging through your days, it could be your mitochondria calling for help. We’ve seen how these tiny powerhouses make ATP, the very energy that runs your body. We’ve also learned how oxidative stress wears them down and why glutathione, the “Master Antioxidant,” is so critical to keeping them strong. Chronic fatigue and other health challenges often can be traced back to mitochondria that are running out of energy, coupled with high oxidative stress. The good news? Nutrients like glutathione, NAC, CoQ10, minerals, and B vitamins can give your cells the boost they need. And with the right testing, you and your practitioner can uncover whether your mitochondria are struggling and create a plan to recharge them. Taking care of your mitochondria isn’t just about building up energy levels to do the things you enjoy—it’s about optimizing your brain, heart, and physical fitness for years to come.

Action Steps to Boost Energy and Beat Fatigue

• Provide nutrients for mitochondrial support: coenzyme Q10, carnitine, B vitamins, lipoic acid, and minerals including iron and magnesium.16
• 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).
• Avoid toxins that deplete your glutathione, such as mercury, cadmium, alcohol, smoke, charred foods, pesticides, and solvents.
• 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 with organic acids, amino acids, and/or blood glutathione.
• Take other supportive antioxidants such as selenium, vitamin C, vitamin E, quercetin, and resveratrol.

 

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.

 

 

References

1. 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
2. Pizzorno J. Glutathione! Integr Med (Encinitas). Feb 2014;13(1):8-12.
3. 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
4. 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
5. Maes M, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Medical science monitor : international medical journal of experimental and clinical research. Apr 2011;17(4):Sc11-5. doi:10.12659/msm.881699
6. Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Increased 8-hydroxy-deoxyguanosine, a marker of oxidative damage to DNA, in major depression and myalgic encephalomyelitis / chronic fatigue syndrome. Neuro endocrinology letters. 2009;30(6):715-22.
7. Richards RS, Roberts TK, McGregor NR, Dunstan RH, Butt HL. Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep. 2000;5(1):35-41. doi:10.1179/rer.2000.5.1.35
8. Puri BK, Agour M, Gunatilake KD, Fernando KA, Gurusinghe AI, Treasaden IH. An in vivo proton neurospectroscopy study of cerebral oxidative stress in myalgic encephalomyelitis (chronic fatigue syndrome). Prostaglandins, leukotrienes, and essential fatty acids. Nov-Dec 2009;81(5-6):303-5. doi:10.1016/j.plefa.2009.10.002
9. Paul BD, Lemle MD, Komaroff AL, Snyder SH. Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome. Proc Natl Acad Sci U S A. Aug 24 2021;118(34)doi:10.1073/pnas.2024358118
10. Shungu DC, Weiduschat N, Murrough JW, et al. Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology. NMR Biomed. Sep 2012;25(9):1073-87. doi:10.1002/nbm.2772
11. Singh A, Naidu PS, Gupta S, Kulkarni SK. Effect of natural and synthetic antioxidants in a mouse model of chronic fatigue syndrome. Journal of medicinal food. Winter 2002;5(4):211-20. doi:10.1089/109662002763003366
12. Aoi W, Ogaya Y, Takami M, et al. Glutathione supplementation suppresses muscle fatigue induced by prolonged exercise via improved aerobic metabolism. Journal of the International Society of Sports Nutrition. 2015;12:7. doi:10.1186/s12970-015-0067-x
13. Zhang S, Wang C, Zhong W, Kemp AH, Guo M, Killpartrick A. Polymerized Whey Protein Concentrate-Based Glutathione Delivery System: Physicochemical Characterization, Bioavailability and Sub-Chronic Toxicity Evaluation. Molecules. Mar 24 2021;26(7)doi:10.3390/molecules26071824
14. Richie JP, Jr., Nichenametla S, Neidig W, et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. European journal of nutrition. Mar 2015;54(2):251-63. doi:10.1007/s00394-014-0706-z
15. Ma S, Ono M, Mizugaki A, Kato H, Miyashita M, Suzuki K. Cystine/Glutamine Mixture Supplementation Attenuated Fatigue during Endurance Exercise in Healthy Young Men by Enhancing Fatty Acid Utilization. Sports (Basel). Sep 27 2022;10(10)doi:10.3390/sports10100147
16. Almannai M, El-Hattab AW, Ali M, Soler-Alfonso C, Scaglia F. Clinical trials in mitochondrial disorders, an update. Molecular genetics and metabolism. Sep-Oct 2020;131(1-2):1-13. doi:10.1016/j.ymgme.2020.10.002
17. Chen LZ, Cai Q, Zheng PF. Mitochondrial metabolic rescue in post-COVID-19 syndrome: MR spectroscopy insights and precision nutritional therapeutics. Front Immunol. 2025;16:1597370. doi:10.3389/fimmu.2025.1597370
18. Naviaux RK. Perspective: Cell danger response Biology-The new science that connects environmental health with mitochondria and the rising tide of chronic illness. Mitochondrion. Mar 2020;51:40-45. doi:10.1016/j.mito.2019.12.005
19. Nicolson GL. Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements. Integr Med (Encinitas). 2014 Aug;13(4):35-43.