Powerful Cell Hack: Mitochondria Supplements for Improved Energy

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Author : Ari Whitten
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Medical Reviewer: Evan Hirsch, MD

Mitochondria Powerful_Cell_Hack

Background on Mitochondria

Eating a healthy, phytonutrient-rich diet, exercising regularly, and getting good quality sleep are vitally important for improving energy levels, it is often difficult to do while balancing the demands of life. This is where supplements can play an essential role in mitochondrial health.

We don’t believe you should rely on supplements to increase energy or fix health issues, but we do think they can play a role in complementing a healthy lifestyle.

A study published in the Journal of the International Society of Sports Nutrition showed that it’s tough to get all the essential vitamins and minerals you need from food alone. This study analyzed the diets of 70 athletes, and every single one was deficient in at least three nutrients. Some diets were missing up to fifteen nutrients! [efn_note]Nicolson, Garth L. “Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements.” Integrative medicine (Encinitas, Calif.) vol. 13,4 (2014): 35-43 [/efn_note] The most common vitamins and minerals lacking in the modern diet are B vitamins, calcium, potassium, iron, zinc, magnesium, and selenium.

Before supplementing, it is vital to find out the cause of your fatigue. Blood tests can help you determine if you have any vitamin or mineral deficiencies. Work with your health care provider to assess your results, decide on a treatment plan for your fatigue, and determine the safety and efficacy of supplements you use.

There are many supplements out there that have a lot of hype and anecdotal feedback but lack scientific evidence, so beware! We will only be focusing here on compounds that have good, trustworthy, science-backed studies for supporting energy levels that are directly linked to cellular energy.

Dietary Supplements Commonly Used for Therapy: Mitochondrial Membrane Support

NT-Factor Phospholipid Complex

One of the most powerful compounds for mitochondrial regeneration. NT-Factors is a compound used in lipid replacement therapy, a method of replacing damaged membrane glycerophospholipids that accumulate during aging and in various clinical conditions in order to restore cellular and mitochondrial function. It has been shown to reduce fatigue by a whopping 24–43% in people with chronic fatigue syndrome [efn_note] Niyazov, D.M. “Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction: Importance of Distinction for Diagnosis and Treatment.” Mol Syndromol. 2016 Jul;7(3):122-37. doi: 10.1159/000446586. [/efn_note] [efn_note] https://www.sciencedaily.com/releases/2017/01/170126093255.htm [/efn_note] [efn_note] Limongelli G, Masarone D, D’Alessandro R, Elliott PM. “Mitochondrial diseases and the heart: an overview of molecular basis, diagnosis, treatment and clinical course.” Future Cardiol. 2012;8(1):71–88. [/efn_note] [efn_note] Victor VM, Apostolova N, Herance R, Hernandez-Mijares A, Rocha M. “Oxidative stress and mitochondrial dysfunction in atherosclerosis: mitochondria-targeted antioxidants as potential therapy.” Curr Med Chem. 2009;16(35):4654–4667. [/efn_note], as well as reduce cancer-associated fatigue in just a few weeks of use. [efn_note] Swerdlow RH. “Brain aging, Alzheimer’s disease, and mitochondria.” Biochim Biophys Acta. 2011;1812(12):1630–1639. [/efn_note] [efn_note] Reddy PH, Reddy TP. “Mitochondria as a therapeutic target for aging and neurodegenerative diseases.” Curr Alzheimer Res. 2011;8(4):393–409. [/efn_note]

Astaxanthin

A  red pigment found in krill and other seafood. Due to its special ability to penetrate inside of cells and incorporate itself inside its mitochondrial membranes, Astaxanthin is known to protect the mitochondria against oxygen radicals, conserve their antioxidant capacity and enhance their energy production efficiency. It is thought to be one of the most effective antioxidants known to man. It can increase blood flow [efn_note] Karbowski M, Neutzner A. “Neurodegeneration as a consequence of failed mitochondrial maintenance.” Acta Neuropathol. 2012;123(2):157–171. [/efn_note], reduce the oxidation of LDL [efn_note] Ghafourifar P, Mousavizadeh K, Parihar MS, Nazarewicz RR, Parihar A, Zenebe WJ. “Mitochondria in multiple sclerosis.” Front Biosci. 2008 Jan;13:3116–3126. [/efn_note], and improve cognitive function. [efn_note] Mao P, Reddy PH. “Is multiple sclerosis a mitochondrial disease?” Biochim Biophys Acta. 2010;1802(1):66–79. [/efn_note]

Astaxanthin also modulates blood glucose [efn_note] Norheim KB, Jonsson G, Omdal R. “Biological mechanisms of chronic fatigue.” Rheumatology (Oxford) 2011;50(6):1009–1018. [/efn_note] increasing levels of Orexin and, hence, energy levels. One study showed that Astaxanthin might even have anti-aging properties. [efn_note] Ma ZA, Zhao Z, Turk J. “Mitochondrial dysfunction and beta-cell failure in type 2 diabetes mellitus.” Exp Diabetes Res. 2012;2012:703538. doi:10.1155/2012/703538. [/efn_note]

As astaxanthin is fat-soluble, it is best taken with a meal containing fats and should be taken either a few hours before or after exercise.

Cofactors in Mitochondrial Energy Production

Cofactors are compounds that assist with biological chemical reactions within the body. These can be vitamins, minerals, or coenzymes that work synergistically with enzymes in the production of ATP (our energy currency) by the mitochondria.

Magnesium

An essential mineral and is considered the second most common deficiency affecting about 70% of the American population. A lack of Magnesium increases blood pressure, reduces glucose tolerance, and causes abnormal neural excitations that impair sleep. [efn_note] Joseph AM, Joanisse DR, Baillot RG, Hood DA. “Mitochondrial dysregulation in the pathogenesis of diabetes: potential for mitochondrial biogenesis-mediated interventions.” Exp Diabetes Res. 2012;2012:642038. doi:10.1155/2012/642038. [/efn_note] The best food sources of Magnesium are leafy greens, nuts, seeds, and cacao. Supplementing with Magnesium can have a calming effect on the body [efn_note] Wang, Zimian et al. “Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure.” The American journal of clinical nutrition vol. 92,6 (2010): 1369-77. doi:10.3945/ajcn.2010.29885 [/efn_note] and may improve sleep quality.

Better sleep means more energy throughout the day. Magnesium can be taken in pill form (as citrate, gluconate, or diglycinate) or rubbed on the body in the form of an oil. Alternatively, you can relax at the end of the day by soaking in a magnesium-rich Epsom salts bath. Magnesium L-threonate is considered a cognitive enhancer. [efn_note] Tarnopolsky, M.A., Raha, S. “Mitochondrial myopathies: diagnosis, exercise intolerance, and treatment options.” Med Sci Sports Exerc. 2005 Dec;37(12):2086-93. [/efn_note] Avoid taking Magnesium, calcium, zinc, and iron at the same time as these minerals compete for absorption.

Coenzyme Q10

Naturally occurring in all cells of the body, although the heart, kidneys, and liver have the highest levels. CoQ10 plays a critical role in energy production and in protecting cells from oxidative damage. [efn_note] Twig G, Shirihai OS. “The interplay between mitochondrial dynamics and mitophagy.” Antioxid Redox Signal. 2011;14(10):1939–1951 [/efn_note] As people with some diseases have reduced levels of this substance, including people who have fibromyalgia [efn_note]Nicolson, G. L. & Ash, M. E. “Lipid Replacement Therapy: a natural medicine approach to replacing damaged lipids in cellular membranes and organelles and restoring function.” Biochim. Biophys. Acta 1838, 1657–1679 (2014). [/efn_note] [efn_note]Nicolson, G. L. & Ellithorpe, R. “Lipid Replacement and Antioxidant Nutritional Therapy for Restoring Mitochondrial Function and Reducing Fatigue in Chronic Fatigue Syndrome and Other Fatiguing Illnesses.” J. Chronic Fatigue Syndr. 13, 57–68 (2006). [/efn_note] [efn_note] L. Nicolson, G., Settineri, R. & Ellithorpe, R. “Lipid Replacement Therapy with a Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Fatigue in Intractable Chronic Fatiguing Illnesses and Chronic Lyme Disease Patients.” IJCM 03, 163–170 (2012) [/efn_note],have survived heart attacks or heart failure [efn_note] Agadjanyan, M. et al. “Nutritional Supplement (NT FactorTM) Restores Mitochondrial Function and Reduces Moderately Severe Fatigue in Aged Subjects.” J. Chronic Fatigue Syndr. 11, 23–36 (2003). [/efn_note] [efn_note] Nicolson, G. L. & Conklin, K. A. “Reversing mitochondrial dysfunction, fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy.” Clin. Exp. Metastasis 25, 161–169 (2008). [/efn_note], have multiple sclerosis [efn_note] Nicolson, G. L. “Lipid replacement/antioxidant therapy as an adjunct supplement to reduce the adverse effects of cancer therapy and restore mitochondrial function.” Pathol. Oncol. Res. 11, 139–144 (2005). [/efn_note] [efn_note] Pashkow, F. J., Watumull, D. G. & Campbell, C. L. “Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease.” Am. J. Cardiol. 101, 58D–68D (2008). [/efn_note], are infertile [efn_note] Goulinet, S. & Chapman, M. J. “Plasma LDL and HDL subspecies are heterogenous in particle content of tocopherols and oxygenated and hydrocarbon carotenoids. Relevance to oxidative resistance and atherogenesis.” Arterioscler. Thromb. Vasc. Biol. 17, 786–796 (1997). [/efn_note] [efn_note] Ito, N., Saito, H., Seki, S., Ueda, F. & Asada, T. “Effects of Composite Supplement Containing Astaxanthin and Sesamin on Cognitive Functions in People with Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Trial.” J. Alzheimers. Dis. 62, 1767–1775 (2018). [/efn_note] [efn_note] Mashhadi, N. S. et al. “Astaxanthin improves glucose metabolism and reduces blood pressure in patients with type 2 diabetes mellitus.” Asia Pac. J. Clin. Nutr. 27, 341–346 (2018). [/efn_note], or suffer migraines. [efn_note] Kidd, Parris. “Astaxanthin, cell membrane nutrient with diverse clinical benefits and anti-aging potential.” Alternative medicine review : a journal of clinical therapeutic vol. 16,4 (2011): 355-64. [/efn_note] [efn_note] Schwalfenberg, G. K. & Genuis, S. J. “The Importance of Magnesium in Clinical Healthcare.” Scientifica  2017, 4179326 (2017). [/efn_note] Researchers have been interested in finding out whether CoQ10 supplements might have health benefits. CoQ10 enhances blood flow (through nitric oxide preservation), protects blood vessels, lowers oxidative stress, and boosts vitality in anyone who suffers from fatigue, but especially those people with the aforementioned conditions. Additionally, statin drugs are known to deplete CoQ10 levels [efn_note] Chollet, D. et al. “Magnesium involvement in sleep: genetic and nutritional models.” Behav. Genet. 31, 413–425 (2001). [/efn_note], so supplementation is mandatory in people taking a statin. [efn_note] Wang, J. et al. “Magnesium L-threonate prevents and restores memory deficits associated with neuropathic pain by inhibition of TNF-α.” Pain Physician. 2013 Sep-Oct;16(5):E563-75. [/efn_note]

Acetyl L-Carnitine (ALCAR)

Acetyl L-Carnitine (ALCAR) is a unique form of the amino acid L-Carnitine that is involved in energy production and mitochondrial biogenesis (the growth and creation of new mitochondria). It is known for boosting energy [efn_note] Saini, Rajiv. “Coenzyme Q10: The essential nutrient.” Journal of pharmacy & bioallied sciences vol. 3,3 (2011): 466-7. doi:10.4103/0975-7406.84471 [/efn_note] [efn_note] Cordero, M. D. et al. “Coenzyme Q10 distribution in blood is altered in patients with fibromyalgia.” Clin. Biochem. 42, 732–735 (2009). [/efn_note] [efn_note]Di Pierro, F., Rossi, A., Consensi, A., Giacomelli, C. & Bazzichi, L. “Role for a water-soluble form of CoQ10 in female subjects affected by fibromyalgia. A preliminary study.” Clin. Exp. Rheumatol. 35 Suppl 105, 20–27 (2017). [/efn_note], improving alertness and cognitive function [efn_note] Cordero, M. D. et al. “Can coenzyme q10 improve clinical and molecular parameters in fibromyalgia?” Antioxid. Redox Signal. 19, 1356–1361 (2013). [/efn_note] [efn_note] Jafari, M., Mousavi, S. M., Asgharzadeh, A. & Yazdani, N. “Coenzyme Q10 in the treatment of heart failure: A systematic review of systematic reviews.” Indian Heart J. 70 Suppl 1, S111–S117 (2018). [/efn_note] and also improves insulin sensitivity [efn_note] Patel, S. P., Sullivan, P. G., Lyttle, T. S. & Rabchevsky, A. G. “Acetyl-L-carnitine ameliorates mitochondrial dysfunction following contusion spinal cord injury.” J. Neurochem. 114, 291–301 (2010). [/efn_note], thus, indirectly increasing levels of Orexin. L-Carnitine has also been shown to effectively reduce depression [efn_note] DiNicolantonio, J. J., Bhutani, J., McCarty, M. F. & O’Keefe, J. H. “Coenzyme Q10 for the treatment of heart failure: a review of the literature.” Open Heart 2, e000326 (2015). [/efn_note], prevent neurological decline and chronic fatigue during aging [efn_note] Sanoobar, M., Dehghan, P., Khalili, M., Azimi, A. & Seifar, F. “Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: A double blind randomized clinical trial.” Nutr. Neurosci. 19, 138–143 (2016). [/efn_note] [efn_note] Sanoobar, M. et al. “Coenzyme Q10 supplementation ameliorates inflammatory markers in patients with multiple sclerosis: a double blind, placebo, controlled randomized clinical trial.” Nutr. Neurosci. 18, 169–176 (2015). [/efn_note] [efn_note] Lafuente, R. et al. “Coenzyme Q10 and male infertility: a meta-analysis.” J. Assist. Reprod. Genet. 30, 1147–1156 (2013). [/efn_note] [efn_note] Xu, Y. et al. “Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial.” Reprod. Biol. Endocrinol. 16, 29 (2018). [/efn_note] [efn_note] Ben-Meir, A. et al. “Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging.” Aging Cell 14, 887–895 (2015). [/efn_note] and improve cardiovascular health. [efn_note] Shoeibi, A. et al. “Effectiveness of coenzyme Q10 in prophylactic treatment of migraine headache: an open-label, add-on, controlled trial.” Acta Neurol. Belg. 117, 103–109 (2017). [/efn_note]

Incidentally, supplementing with ALCAR often results in fat loss because those taking it to tend to become more physically active due to the increased energy and vitality it yields.

D-Ribose

A type of simple, five-carbon sugar that our bodies make. It is an essential component of adenosine triphosphate (ATP), which supplies energy to our cells. Normal, healthy tissue can make all the ribose it needs, but ATP production is hindered by inadequate ribose when we are stressed by overexertion. ATP production can drop by as much as 20% after a strenuous workout and may take up to 72 hours to fully recover. [efn_note] Sándor, P. S. et al. “Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial.” Neurology 64, 713–715 (2005). [/efn_note] [efn_note] Littarru GP, Tiano L. “Clinical aspects of coenzyme Q10: an update.” Nutrition. 2010;26(3):250–254. [/efn_note]. Ribose supplementation may also help people who have suffered from heart disease or stroke. [efn_note] Orsucci D, Mancuso M, Ienco EC, LoGerfo A, Siciliano G. “Targeting mitochondrial dysfunction and neurodegeneration by means of coenzyme Q10 and its analogues.” Curr Med Chem. 2011;18(26):4053–4064. [/efn_note] [efn_note] Rosenfeldt F, Hilton D, Pepe S, Krum H. “Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure.” Biofactors. 2003;18(1–4):91–100. [/efn_note] [efn_note] Deichmann, R., Lavie, C. & Andrews, S. “Coenzyme q10 and statin-induced mitochondrial dysfunction.” Ochsner J. 10, 16–21 (2010). [/efn_note] Studies have also shown that D-ribose significantly reduced clinical symptoms in patients suffering from fibromyalgia and chronic fatigue syndrome. [efn_note] Skarlovnik, A., Janić, M., Lunder, M., Turk, M. & Šabovič, M. “Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study.” Med. Sci. Monit. 20, 2183–2188 (2014). [/efn_note] Ribose cannot be found in food, so supplementing with it can have dramatic results, under the right conditions.

Creatine

Creatine is among the most well-researched and effective supplements. Athletes, bodybuilders, and military personnel use dietary creatine as an ergogenic aid to boost physical performance in sports involving short bursts of high-intensity muscle activity. Creatine is thought to improve strength, increase lean muscle mass [efn_note] Nicassio, L. et al. “Dietary supplementation with acetyl-l-carnitine counteracts age-related alterations of mitochondrial biogenesis, dynamics and antioxidant defenses in brain of old rats.” Exp. Gerontol. 98, 99–109 (2017). [/efn_note] [efn_note] Patel, S. P., Sullivan, P. G., Lyttle, T. S. & Rabchevsky, A. G. “Acetyl-L-carnitine ameliorates mitochondrial dysfunction following contusion spinal cord injury.” J. Neurochem. 114, 291–301 (2010). [/efn_note] [efn_note] Rosca, M. G., Lemieux, H. & Hoppel, C. L. “Mitochondria in the elderly: Is acetylcarnitine a rejuvenator?” Adv. Drug Deliv. Rev. 61, 1332–1342 (2009). [/efn_note], and help the muscles recover more quickly during exercise. It has also been shown to have neuroprotective and cardioprotective benefits. [efn_note] Rump, T. J. et al. “Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain.” Free Radic. Biol. Med. 49, 1494–1504 (2010). [/efn_note] [efn_note] Scafidi, S., Racz, J., Hazelton, J., McKenna, M. C. & Fiskum, G. “Neuroprotection by acetyl-L-carnitine after traumatic injury to the immature rat brain.” Dev. Neurosci. 32, 480–487 (2010). [/efn_note] and increase cognitive function [efn_note] Xu, Y. et al. “L-carnitine treatment of insulin resistance: A systematic review and meta-analysis.” Adv. Clin. Exp. Med. 26, 333–338 (2017). [/efn_note] [efn_note] Veronese, N. et al. “Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis.” Psychosom. Med. 80, 154–159 (2018). [/efn_note]

Creatine is most effective when taken immediately after exercise with a meal containing carbohydrates.

Activators of Mitochondrial Biogenesis and Defense

Amla

(Phyllanthus Emblica) is also known as the Indian Gooseberry and is used in Ayurvedic medicine to treat many ailments. The health benefits of Amla berry can mostly be attributed to its high whole food vitamin C content and its impressive antioxidant abilities. Alma has been shown to have antiatherogenic, adaptogenic, cardioprotective, gastroprotective, antianemia, anti hypercholesterolemia, antidiarrheal, and neuroprotective properties. [efn_note] Rai, G. et al. “Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer’s dementia.” Curr. Med. Res. Opin. 11, 638–647 (1990). [/efn_note] It may also be useful in the prevention and treatment of cancer. [efn_note] Rai, G. et al. “Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer’s dementia.” Curr. Med. Res. Opin. 11, 638–647 (1990). [/efn_note]

Taurine 

A sulfur-containing amino acid naturally found in animal proteins, including meat, seafood, dairy, and eggs. It is essential for cardiovascular function [efn_note] Passeri, M. et al. “Acetyl-L-carnitine in the treatment of mildly demented elderly patients.” Int. J. Clin. Pharmacol. Res. 10, 75–79 (1990). [/efn_note] and the development and function of skeletal muscle, the retina, and the brain. [efn_note] Thal, L. J. et al. “A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer’s disease.” Neurology 47, 705–711 (1996).[/efn_note]

Through signaling neurotransmitters in the brain, such as GABA and BDNF, it has anti-anxiety and antidepressant effects. It also affects Orexin by modulating and improving glucose sensitivity and glucose control. Eye, skin, endothelial, and kidney health can be improved by supplementing with taurine, especially in diabetics. Taurine is also essential for the proper function of mitochondria. [efn_note] Tomassini, V. et al. “Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial.” J. Neurol. Sci. 218, 103–108 (2004). [/efn_note] [efn_note] Plioplys, A. V. & Plioplys, S. “Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome.” Neuropsychobiology 35, 16–23 (1997). [/efn_note]

Alpha Lipoic Acid (ALA) – is a mitochondrial compound involved in energy metabolism. It is one of the most potent antioxidants produced naturally by the body but also found in a variety of foods and in supplement form. It reduces inflammation [efn_note] Hellsten, Y., Skadhauge, L. & Bangsbo, J. “Effect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans.” Am. J. Physiol. Regul. Integr. Comp. Physiol. 286, R182–8 (2004). [/efn_note] [efn_note] Seifert, J. G., Brumet, A. & St Cyr, J. A. “The influence of D-ribose ingestion and fitness level on performance and recovery.” J. Int. Soc. Sports Nutr. 14, 47 (2017). [/efn_note] and thereby directly improves energy levels. ALA can also reduce blood glucose levels when taken with a meal and thus maintain levels of the hormone Orexin, which promotes wakefulness.

Turmeric

Containing Curcumin, a yellow, bio-active compound known to possess powerful antioxidant and anti-inflammatory properties. It can help reduce depression and anxiety [efn_note] Omran, H., Illien, S., MacCarter, D., St Cyr, J. & Lüderitz, B. “D-Ribose improves diastolic function and quality of life in congestive heart failure patients: a prospective feasibility study.” Eur. J. Heart Fail. 5, 615–619 (2003). [/efn_note] [efn_note] MacCarter, D. et al. “D-ribose aids advanced ischemic heart failure patients.” Int. J. Cardiol. 137, 79–80 (2009). [/efn_note], slow cognitive decline with aging, promote cardiovascular health, reduce the risk of diabetes, and alleviate other inflammatory conditions, such as arthritis. Curcumin protects and stabilizes mitochondrial membranes and plays a role in mitochondrial biogenesis, thus improving energy levels.

To improve its bioavailability, Curcumin can be taken with piperine (found in high concentrations in black pepper), or as NovaSol®, CurcuWin® (136-fold), or LongVida®. – These are the most recommended forms.

Green Tea

Containing ECGC (epigallocatechin-3-gallate), a potent phytochemical with a host of health benefits ranging from cardioprotective [efn_note] Pliml, W. et al. “Effects of ribose on exercise-induced ischaemia in stable coronary artery disease.” Lancet 340, 507–510 (1992). [/efn_note] [efn_note] Teitelbaum, JE. et al. “The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study.”  J Altern Complement Med. 2006 Nov;12(9):857-62. [/efn_note], neuroprotective [efn_note] Butts, J., Jacobs, B. & Silvis, M. “Creatine Use in Sports.” Sports Health 10, 31–34 (2018). [/efn_note] [efn_note] Dempsey, R. L., Mazzone, M. F. & Meurer, L. N. “Does oral creatine supplementation improve strength?” A meta-analysis. J. Fam. Pract. 51, 945–951 (2002). [/efn_note] and liver-protective to anti-diabetic [efn_note] Chilibeck, P. D., Kaviani, M., Candow, D. G. & Zello, G. A. “Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: a meta-analysis.” Open Access J Sports Med 8, 213–226 (2017). [/efn_note], anti-obesogenic [efn_note] Ainsley Dean, P. J., Arikan, G., Opitz, B. & Sterr, A. “Potential for use of creatine supplementation following mild traumatic brain injury.” Concussion 2, CNC34 (2017). [/efn_note] [efn_note] Korpacheva, O. V., Dolgikh, V. T., Shikunova, L. G. & Zolotov, A. N. “Cardioprotective effect of exogenous creatine phosphate in acute hemorrhage.” Anesteziol. Reanimatol. 13–16 (2002). [/efn_note] [efn_note] Avgerinos, K. I., Spyrou, N., Bougioukas, K. I. & Kapogiannis, D. “Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials.” Exp. Gerontol. 108, 166–173 (2018). [/efn_note], anti-fatigue and even anti-carcinogenic effects! [efn_note] Rawson, E. S. & Venezia, A. C. “Use of creatine in the elderly and evidence for effects on cognitive function in young and old.” Amino Acids 40, 1349–1362 (2011). [/efn_note] [efn_note] Baliga, MS., Dsouza, JJ. “Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer.” Eur J Cancer Prev. 2011 May;20(3):225-39. doi: 10.1097/CEJ.0b013e32834473f4. [/efn_note]

ECGC works synergistically with L-Theanine to reduce anxiety and stress and is overall a very powerful protector of Mitochondria.

In a 12-week double-blind trial published in the American Journal of Clinical Nutrition, researchers gave 38 overweight adults, a daily polyphenol supplement, containing 282 milligrams of ECGC and 80 milligrams of Resveratrol (found in grape skins), or a placebo pill. People taking the polyphenol supplement had a highly significant increase in the function of mitochondria in their muscles compared to people given a placebo.

PQQ

Pyrroloquinoline quinone is a redox agent (it reduces and oxidizes), which is capable of reducing oxidation by working synergistically with Glutathione.

It is found naturally in soil and foods such as kiwifruit, as well as in human breast milk. PQQ is known for preventing the development of damaging proteins associated with Parkinson’s disease and can stimulate the release of nerve growth factor cells in the brain. [efn_note]Jong, C. J., Ito, T., Prentice, H., Wu, J.-Y. & Schaffer, S. W. “Role of Mitochondria and Endoplasmic Reticulum in Taurine-Deficiency-Mediated Apoptosis.” Nutrients 9, (2017). [/efn_note] It also supports mitochondrial function [efn_note] Hansen, S. H., Andersen, M. L., Cornett, C., Gradinaru, R. & Grunnet, N. “A role for taurine in mitochondrial function.” J. Biomed. Sci. 17 Suppl 1, S23 (2010). [/efn_note] and mitochondrial biogenesis. [efn_note] Xu, Yan-Jun et al. “The potential health benefits of taurine in cardiovascular disease.” Experimental and clinical cardiology vol. 13,2 (2008): 57-65. [/efn_note] [efn_note] Ripps, H. & Shen, W. “Review: taurine: a ‘very essential’ amino acid.” Mol. Vis. 18, 2673–2686 (2012). [/efn_note]

NAD + regenerators

NAD + stands for nicotinamide adenine dinucleotide. It is a coenzyme found in all living cells. NAD is used to power metabolism by enabling the mitochondria to convert the food we eat into the energy our body needs to sustain all its functions. It also repairs damaged DNA, fortifies the cells’ defense systems, and sets the circadian rhythm.

However, the amount of NAD+ in your body naturally falls with age. [efn_note] Akbari, Maryam et al. “The effects of alpha-lipoic acid supplementation on inflammatory markers among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials.” Nutrition & metabolism vol. 15 39. 5 Jun. 2018, doi:10.1186/s12986-018-0274-y [/efn_note] Lower levels of NAD+ are thought to impair biological functions important to health, which might contribute to age-related diseases. It’s believed that increasing NAD+ through supplementation may improve symptoms and/or delay these conditions.

The following supplements help maintain/boost levels of NAD:

Citrus Bioflavonoids

Phytonutrients found in citrus fruit. Hesperidin is the primary bioactive compound in orange peels, alongside naringenin. They are powerful antioxidant and anti-inflammatory molecules [efn_note] Liu, J. “The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview.” Neurochem Res. 2008 Jan;33(1):194-203. Epub 2007 Jun 29. [/efn_note] [efn_note] Ng, Q. X., Koh, S. S. H., Chan, H. W. & Ho, C. Y. X. “Clinical Use of Curcumin in Depression: A Meta-Analysis.” J. Am. Med. Dir. Assoc. 18, 503–508 (2017). [/efn_note] capable of protecting against several degenerative diseases and particularly brain diseases. [efn_note] Noorafshan, A., Vafabin, M., Karbalay-Doust, S. & Asadi-Golshan, R. “Efficacy of Curcumin in the Modulation of Anxiety Provoked by Sulfite, a Food Preservative, in Rats.” Prev Nutr Food Sci 22, 144–148 (2017). [/efn_note] These effects are mediated, in part, by their ability to prevent mitochondrial dysfunction and oxidative stress. [efn_note] Babu, P. V. A. & Liu, D. “Green tea catechins and cardiovascular health: an update.” Curr. Med. Chem. 15, 1840–1850 (2008). [/efn_note]

Flavonoids are also able to protect endothelial cells against a high glucose-induced decrease in NAD+ [efn_note] Bhardwaj, P. & Khanna, D. “Green tea catechins: defensive role in cardiovascular disorders.” Chin. J. Nat. Med. 11, 345–353 (2013). [/efn_note].

Resveratrol

A polyphenol found in red wine that is associated with life extension and some of the health benefits of wine consumption. [efn_note] Ortiz-López, L. et al. “Green tea compound epigallo-catechin-3-gallate (EGCG) increases neuronal survival in adult hippocampal neurogenesis in vivo and in vitro.” Neuroscience 322, 208–220 (2016). [/efn_note] It is produced in grape skins, peanuts, and some berries as a defense against toxins. It is a potent antioxidant that can protect against heart disease and insulin resistance [efn_note] Pervin, M. et al. “Beneficial Effects of Green Tea Catechins on Neurodegenerative Diseases.” Molecules 23, (2018). [/efn_note], while also increasing blood flow (and oxygen and nutrient delivery) to the brain. [efn_note] Park, J.-H., Bae, J.-H., Im, S.-S. & Song, D.-K. “Green tea and type 2 diabetes.” Integr Med Res 3, 4–10 (2014). [/efn_note]

Moreover, unlike other antioxidants that interfere with exercise-induced adaptations [efn_note] Rains, T. M., Agarwal, S. & Maki, K. C. “Antiobesity effects of green tea catechins: a mechanistic review.” J. Nutr. Biochem. 22, 1–7 (2011). [/efn_note], Resveratrol appears to enhance the physiological benefits of exercise. [efn_note] Hursel, R. & Westerterp-Plantenga, M. S. “Catechin- and caffeine-rich teas for control of body weight in humans.” Am. J. Clin. Nutr. 98, 1682S–1693S (2013). [/efn_note] [efn_note] Hursel, R., Viechtbauer, W. & Westerterp-Plantenga, M. S. “The effects of green tea on weight loss and weight maintenance: a meta-analysis.” Int. J. Obes.  33, 956–961 (2009). [/efn_note]

Quercetin

A well-known bioflavonoid found in fruits and vegetables, particularly onions and apples. It is a potent antioxidant and anti-inflammatory molecule that is involved in mitochondrial energy production, the protection of mitochondria from oxidative stress [efn_note] Cooper, R., Morré, D. J. & Morré, D. M. “Medicinal benefits of green tea: part II. review of anticancer properties.” J. Altern. Complement. Med. 11, 639–652 (2005). [/efn_note] [efn_note] Lambert, J. D. “Does tea prevent cancer? Evidence from laboratory and human intervention studies.” Am. J. Clin. Nutr. 98, 1667S–1675S (2013). [/efn_note] and mitochondrial biogenesis. It is also involved in helping the mitochondria regenerate NAD+, which is vital for energy production.

N-acetyl-Cysteine (NAC)

An immediate precursor to the most potent antioxidant that our body makes, glutathione. NAC also promotes detoxification and acts directly as a scavenger of free radicals. [efn_note] Murase, K. et al. “Stimulation of nerve growth factor synthesis/secretion in mouse astroglial cells by coenzymes.” Biochem Mol Biol Int. 1993 Jul;30(4):615-21. [/efn_note]

Studies have shown that it can increase muscle performance and minimize muscle fatigue during exercise [efn_note] Harris, C. B. et al. “Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects.” J. Nutr. Biochem. 24, 2076–2084 (2013). [/efn_note], as well as prevent the appearance of DNA damage, the decrease in mitochondrial respiration, and the loss of cellular levels of NAD+.[efn_note] Chowanadisai, W. et al. “Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression.” J. Biol. Chem. 285, 142–152 (2010). [/efn_note]

Niacin and Nicotinamide

Two major forms of Vitamin B3 that are precursors of NAD+. They are known to boost NAD+ metabolism and stimulate the activity of certain enzymes that have been linked to numerous health benefits, including resistance to weight gain, improved control of blood sugar and cholesterol, reduced nerve damage, and a longer lifespan.

NAD+ is not bioavailable, meaning it can’t be taken orally and still survive the digestion process, therefore supplementing with its precursors, which do survive digestion, is necessary. [efn_note] Hwang, P. & Willoughby, D. S. “Mechanisms Behind Pyrroloquinoline Quinone Supplementation on Skeletal Muscle Mitochondrial Biogenesis: Possible Synergistic Effects with Exercise.” J. Am. Coll. Nutr. 1–11 (2018). [/efn_note] Of the various precursors of NAD+, Nicotinamide is one of the most efficient. [efn_note] Massudi, H. et al. “Age-associated changes in oxidative stress and NAD+ metabolism in human tissue.” PLoS One. 2012;7(7):e42357. doi: 10.1371/journal.pone.0042357. [/efn_note]

Reduce Stress with Adaptogens and Medicinal Mushrooms

Adaptogens

Adaptogens are herbs that support the body’s ability to accommodate varying physical and emotional stresses. As stress can cause very real physical changes in the body, including harming the neurological, endocrine, and immune systems, supplementing with adaptogens can significantly improve mood and energy levels.

Research shows adaptogens can combat fatigue, enhance mental performance, and ease depression and anxiety. [efn_note] Tejada, S. et al. “Potential Anti-inflammatory Effects of Hesperidin from the Genus Citrus.’ Curr. Med. Chem. 25, 4929–4945 (2018). [/efn_note]

Rhodiola Rosea

An adaptogen used in traditional Chinese medicine. Studies have shown that it very reliably reduces symptoms of fatigue and helps with depression, which is also commonly linked to fatigue. [efn_note] Manchope, M. F., Casagrande, R. & Verri, W. A., Jr. “Naringenin: an analgesic and anti-inflammatory citrus flavanone.” Oncotarget 8, 3766–3767 (2017). [/efn_note] [efn_note] Benavente-García, O. & Castillo, J. “Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity.” J. Agric. Food Chem. 56, 6185–6205 (2008). [/efn_note]

By increasing dopamine signaling and thereby activating Orexin, it increases energy and wakefulness. In addition, studies have shown that it improves cognitive and physical performance and promotes longevity.

Ashwagandha

One of the most important adaptogenic herbs used in traditional Indian Ayurvedic medicine. It has been found to increase energy by increasing the body’s resilience to physical and mental stress. [efn_note] Kumar, A., Prakash, A. & Dogra, S. “Naringin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress induced by D-galactose in mice.” Food Chem. Toxicol. 48, 626–632 (2010). [/efn_note] It has also been shown to improve thyroid function [efn_note] Boesten, Daniëlle M P H J et al. “Protective Pleiotropic Effect of Flavonoids on NAD⁺ Levels in Endothelial Cells Exposed to High Glucose.” Oxidative medicine and cellular longevity vol. 2015 (2015): 894597. doi:10.1155/2015/894597 [/efn_note] and improve physical performance in both sedentary people and athletes. Ashwagandha root extract is the preferred form of supplementation.

Panax Ginseng

A well-known Chinese traditional medicine that has gained recognition in the West during the last decade. It is popularly known to increase libido and appears to be effective for mood, immunity, and cognition. In addition, Panax Ginseng modulates and reduces blood glucose, which helps maintain levels of Orexin and thus promotes wakefulness. [efn_note] Pezzuto, J. M. “Resveratrol: Twenty Years of Growth, Development and Controversy.” Biomol. Ther.  27, 1–14 (2019). [/efn_note] Panax Ginseng has been shown to work synergistically with Gingko Biloba (another Chinese, antioxidant-rich herb used to enhance brain health and treat a variety of conditions).

Reishi Mushrooms

A rare mushroom that grows at the base of deciduous trees. It is known to have numerous health benefits, including boosting the immune system, relieving symptoms of chronic fatigue, and even treating cancer. [efn_note] Xia, N., Daiber, A., Förstermann, U. & Li, H. “Antioxidant effects of resveratrol in the cardiovascular system.” Br. J. Pharmacol. 174, 1633–1646 (2017). [/efn_note]

It is no surprise then that Reishi is known as the ancient “Mushroom of Immortality.” Regular, small-doses calms the body and may help regulate the body’s natural circadian rhythm. Reishi is also used in herbal medicine as an adaptogen, helping your body adapt to stress and improve energy levels.

Cordyceps

A fungus that lives on certain caterpillars in the high mountain regions of China. Known as Himalayan Gold because it is often farmed in the Himalayan plateaus, Cordyceps has long been used in ancient Chinese and Tibetan medicine for curing diarrhea, headache, cough, rheumatism, liver disease, kidney disease, and much more. Clinical studies have shown improvements in the level of fatigue experienced by older adults supplementing with Cordyceps. [efn_note] Carrizzo, A. et al. “Antioxidant effects of resveratrol in cardiovascular, cerebral and metabolic diseases.” Food Chem. Toxicol. 61, 215–226 (2013). [/efn_note]

Cordyceps are thought to increase the body’s production of Adenosine Triphosphate (ATP), which is the primary energy carrier of the body. In another study, healthy elderly volunteers that were administered with Cordyceps while exercising on stationary bicycles showed significant increases in energy and oxygen-carrying capacity (VO2 max). [efn_note] Merry, T. L. & Ristow, M. “Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training?” J. Physiol. 594, 5135–5147 (2016). [/efn_note]

If you are looking to feel less tired or have more energy, adding dried and powdered Cordyceps to your coffee will probably help. Being rich in amino acids and vitamins like B1, B2, B12, and K, Cordyceps is full of energy-boosting nutrients. [efn_note] Kan, N.-W. et al. “The Synergistic Effects of Resveratrol combined with Resistant Training on Exercise Performance and Physiological Adaption.” Nutrients 10, (2018). [/efn_note]

Again, please be cautious if you take anti-hypertensive or anti-coagulant medication and speak with your health care provider before supplementation.

Conclusion

This is by no means an exhaustive list of supplements that enhance energy. For more information read the article titled “The Top Science-Backed Supplements For Energy Enhancement.”

Supplements can definitely help you stay alert and energized throughout the day, but they are no substitute to a solid foundation of regular exercise,  quality sleep, and a phytonutrient-rich diet. Supplements are after all supplements, meaning they are supplementary to optimal nutrition and lifestyle habits. There really is no way to replace a nutritious diet as foods often contain an array of vitamins, minerals, and phytonutrients that work synergistically with one another.

Having said that, you can see that many of the vitamins and supplements listed above have myriad unique positive side effects, beyond increasing energy, and are worthy compliments to a healthy lifestyle. Talk to your healthcare provider to assess your unique situation before starting any supplement regime to help support your powerhouse: your mitochondria.

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Medically Reviewed ByEvan Hirsch, MD

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