The Science Behind Fatigue. And How Can You Combat It.

With Zeynep Ozdemir, Nutrition Specialist

(5.5 min read)

Put rest on a pedestal.

Better sleep and rested body are the foundation of health.

The rise in fatigue can largely be traced back to the digital age, which has reshaped our sleep patterns and increased our exposure to blue light, disrupting circadian rhythms. Additionally, high-stress work environments contribute to chronic stress, a primary driver of fatigue. Sedentary behavior and suboptimal diets further exacerbate the issue by limiting necessary nutrients and physical activity that are crucial for sustaining energy levels and overall health. The consequences of these factors extend beyond discomfort, significantly impairing our daily functions and health.

This blog dissects the underlying causes and explores the physiological consequences of fatigue, rooted in scientific research, to provide a detailed understanding of this condition that affects so many.

The Effects of Fatigue on Daily Life and Health

Fatigue is more than an inconvenience; it substantially diminishes cognitive functions, such as memory and decision-making, lowers productivity, and increases the risk of accidents. Long-term, it weakens the immune system, heightens susceptibility to illnesses, and escalates the risk of mental health disorders like depression and anxiety, impacting life quality and emotional well-being. (1, 2, 3, 4)

To understand these impacts fully, we must delve into the physiological mechanisms at play, which explain how and why fatigue manifests in our bodies.

The Scientific Basis of Fatigue

Physiological Mechanisms of Fatigue: How and Why Does It Occur?

Fatigue stems from a complex interaction of biological processes indicating energy deficits or imbalances in recovery and stress. Biochemically, it can result from adenosine buildup, a byproduct of cellular energy use that reduces neuronal activity and promotes sleep. Moreover, oxidative stress and inflammation disrupt cellular operations and energy production, contributing to fatigue. (5)

Hormones and Fatigue

Cortisol, often called the stress hormone, increases glucose in the bloodstream, providing immediate energy during stressful situations. However, prolonged elevation can lead to chronic fatigue as the body depletes its reserves. (6, 7)

Melatonin, produced in response to darkness, signals the body to prepare for sleep, facilitating the onset and quality of rest, which is crucial for recovery and energy renewal. (8)

Thyroid hormones, which regulate metabolic rate, can cause fatigue when levels are too low or too high. (9)

Similarly, imbalances in insulin following poor dietary choices can lead to fluctuating energy levels and fatigue. (10, 11)

Growth hormone, released during sleep, plays a vital role in tissue repair and muscle growth, impacting energy levels upon waking. (12, 13)

The Role of Sleep Quality and Duration on Fatigue

Quality sleep is crucial for physical restoration, memory consolidation, and hormonal balance. Disrupted or insufficient sleep impairs these processes, leading to significant fatigue. The restorative phases of sleep are critical as the body repairs tissues and cells; missing these phases accumulates sleep debt, perpetuating fatigue and associated health risks. (14)

Strategies to Combat Fatigue

To effectively combat fatigue, integrating strategic lifestyle changes and natural remedies can provide significant benefits. Here’s how:

1.   Nutrition

Balanced dietary choices directly influence energy levels and combat fatigue. (10)

●      Consuming foods rich in complex carbohydrates, like whole grains and legumes, provides a steady release of glucose, essential for sustained energy. (15)

●      Proteins from lean meats and plant-based sources support neurotransmitter functions, which are crucial for maintaining alertness. (16, 17)

●      Additionally, incorporating foods high in omega-3 fatty acids, such as fish and flaxseeds, can reduce inflammation, a known contributor to fatigue. (18)

2.   Sleep Hygiene

Effective sleep hygiene is paramount for combating fatigue. Establishing a regular sleep schedule by going to bed and waking up at consistent times sets the body’s internal clock, enhancing sleep quality. (14, 19)

Creating a sleep-conducive environment (dark, quiet, and cool) can significantly improve sleep onset and depth. Limiting exposure to screens and blue light before bedtime is also crucial, as it helps maintain the natural production of melatonin, the hormone that regulates sleep. (19, 20)

3.   Physical Activity

Regular physical activity is essential in fighting fatigue. Exercise increases heart rate and circulation, driving oxygen and nutrients to muscles and organs, which invigorates the body. It also stimulates the release of endorphins, chemicals in the brain that act as natural painkillers and mood elevators, reducing stress and improving sleep. (21, 22)

4.   Adaptogens and Natural Supplements

Adaptogens regulate the body’s stress response by targeting the hypothalamic-pituitary-adrenal (HPA) axis, which is central to the body's response to stress. They modulate the secretion of stress hormones like cortisol and adrenaline, enhancing the body's ability to maintain homeostasis under stress. This reduces the physiological impact of stress, which can deplete energy levels and lead to fatigue. (23, 24, 25)

By upregulating cellular defense mechanisms such as heat shock proteins and antioxidant enzymes, adaptogens help protect cells from stress-induced damage and improve overall resilience, allowing for better energy conservation and utilization. (25)

Examples of Adaptogens:

●      Ashwagandha: Reduces cortisol levels and improves stress resilience. (26)

●      Rhodiola Rosea: Increases energy, stamina, and mental capacity. (27)

●      Ginseng: Enhances physical performance and alleviates fatigue. (28, 29)

●      Saffron: Boosts mood by increasing serotonin and dopamine levels. (30, 31)

Supplements enhance metabolic and physiological functions crucial for energy production, recovery, and overall health. They support essential biochemical reactions, maintain cellular integrity, and ensure the efficient use of nutrients, which are vital for combating fatigue.

Examples of Supplements:

● B Vitamins: Key facilitators in energy metabolism, B vitamins such as B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) are integral in the Krebs cycle and electron transport chain, processes essential for ATP production. They also play a role in the synthesis of neurotransmitters that affect brain function and energy levels. (32, 33)

● Magnesium: A cofactor in over 300 enzyme systems, magnesium is crucial for protein synthesis, muscle and nerve function, and the regulation of blood glucose levels. It also supports the synthesis of ATP, providing the energy required for many chemical reactions in the body. (33, 34, 35)

● Iron: Essential for the formation of hemoglobin, which transports oxygen from the lungs to the body's tissues. Iron deficiency can lead to anemia, characterized by fatigue and decreased aerobic capacity, as tissues receive less oxygen. (33, 36)

● Coenzyme Q10: Located in mitochondria, Coenzyme Q10 aids in electron transport and ATP production. It also serves as an antioxidant, protecting cells from oxidative stress and damage, which can lead to energy depletion. (37, 38)

● Omega-3 Fatty Acids: These fatty acids reduce inflammation, which if persistent, can lead to chronic fatigue. They also play a role in cellular membrane fluidity, influencing hormone binding and cellular signaling, which are crucial for maintaining energy homeostasis. (39, 40)

5.   Mindfulness and Meditation

Mindfulness and meditation have demonstrated efficacy in reducing fatigue by modulating stress responses. These practices activate the parasympathetic nervous system, which counters the body’s stress-induced 'fight or flight' response. (41)

Scientific studies reveal that mindfulness can decrease cortisol levels, the hormone associated with stress and fatigue, thereby enhancing overall calmness and reducing physical signs of stress. Also, meditation supports cognitive restoration, which is vital in managing mental fatigue and preserving energy levels throughout the day. (42, 43)

6.   Time Management and Establishing a Work-life Balance

Efficient time management is critical in mitigating fatigue by preventing work-related overload and stress, which are major contributors to exhaustion. Structuring daily activities with adequate breaks and prioritized tasks can reduce cognitive overload, a significant factor in fatigue. Moreover, maintaining a healthy work-life balance is essential, as it allows for necessary psychological recovery. Research indicates that individuals with balanced lifestyles experience lower levels of cortisol, better sleep patterns, and higher overall energy levels. (44, 45, 46)

References:

1. Menzies, V., Kelly, D. L., Yang, G. S., Starkweather, A., & Lyon, D. E. (2021). A systematic review of the association between fatigue and cognition in chronic noncommunicable diseases. Chronic illness, 17(2), 129–150. https://doi.org/10.1177/1742395319836472

2. Jia, A., Guo, X., & Tian, S. (2022). Experimental study on the influence of mental fatigue on risk decision-making of miners. Scientific reports, 12(1), 11902. https://doi.org/10.1038/s41598-022-14045-9

3. Salleh M. R. (2008). Life event, stress and illness. The Malaysian journal of medical sciences : MJMS, 15(4), 9–18.

4. Caldwell, J. A., Caldwell, J. L., Thompson, L. A., & Lieberman, H. R. (2018). Fatigue and its management in the workplace. Neuroscience & Biobehavioral Reviews, 96, 272-289. https://doi.org/10.1016/j.neubiorev.2018.10.024

5. Schirinzi, E., Ricci, G., Torri, F., Mancuso, M., & Siciliano, G. (2023). Biomolecules of Muscle Fatigue in Metabolic Myopathies. Biomolecules, 14(1). https://doi.org/10.3390/biom14010050

6. Hannibal, K. E., & Bishop, M. D. (2014). Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation. Physical therapy, 94(12), 1816–1825. https://doi.org/10.2522/ptj.20130597

7. Thau L, Gandhi J, Sharma S. Physiology, Cortisol. [Updated 2023 Aug 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538239/

8. Masters, A., Pandi-Perumal, S. R., Seixas, A., Girardin, J. L., & McFarlane, S. I. (2014). Melatonin, the Hormone of Darkness: From Sleep Promotion to Ebola Treatment. Brain disorders & therapy, 4(1), 1000151. https://doi.org/10.4172/2168-975X.1000151

9. Shahid MA, Ashraf MA, Sharma S. Physiology, Thyroid Hormone. [Updated 2023 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK500006/

10. Azzolino, D., Arosio, B., Marzetti, E., Calvani, R., & Cesari, M. (2020). Nutritional Status as a Mediator of Fatigue and Its Underlying Mechanisms in Older People. Nutrients, 12(2), 444. https://doi.org/10.3390/nu12020444

11. Sapra A, Bhandari P. Diabetes. [Updated 2023 Jun 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551501/

12. Zaffanello, M., Pietrobelli, A., Cavarzere, P., Guzzo, A., & Antoniazzi, F. (2023). Complex relationship between growth hormone and sleep in children: Insights, discrepancies, and implications. Frontiers in Endocrinology, 14. https://doi.org/10.3389/fendo.2023.1332114

13. Gohil A, Eugster E. Growth Hormone Deficiency and Excessive Sleepiness: A Case Report and Review of the Literature. Pediatr Endocrinol Rev. 2019 Sep;17(1):41-46. doi: 10.17458/per.vol17.2019.ge.ghdeficiencyandsleepiness. PMID: 31599135; PMCID: PMC7262958.

14. Eugene, A. R., & Masiak, J. (2015). The Neuroprotective Aspects of Sleep. MEDtube Science, 3(1), 35. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651462/

15. Holesh JE, Aslam S, Martin A. Physiology, Carbohydrates. [Updated 2023 May 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459280/

16. Institute of Medicine (US) Committee on Military Nutrition Research. The Role of Protein and Amino Acids in Sustaining and Enhancing Performance. Washington (DC): National Academies Press (US); 1999. 14, Amino Acid and Protein Requirements: Cognitive Performance, Stress, and Brain Function. Available from: https://www.ncbi.nlm.nih.gov/books/NBK224629/

17. Teleanu, R. I., Niculescu, A. G., Roza, E., Vladâcenco, O., Grumezescu, A. M., & Teleanu, D. M. (2022). Neurotransmitters-Key Factors in Neurological and Neurodegenerative Disorders of the Central Nervous System. International journal of molecular sciences, 23(11), 5954. https://doi.org/10.3390/ijms23115954

18. Zivkovic, A. M., Telis, N., German, J. B., & Hammock, B. D. (2011). Dietary omega-3 fatty acids aid in the modulation of inflammation and metabolic health. California agriculture, 65(3), 106–111. https://doi.org/10.3733/ca.v065n03p106

19. Panel on Research Methodologies and Statistical Approaches to Understanding Driver Fatigue Factors in Motor Carrier Safety and Driver Health; Committee on National Statistics; Board on Human-Systems Integration; Division of Behavioral and Social Sciences and Education; Transportation Research Board; National Academies of Sciences, Engineering, and Medicine. Commercial Motor Vehicle Driver Fatigue, Long-Term Health, and Highway Safety: Research Needs. Washington (DC): National Academies Press (US); 2016 Aug 12. 3, Consequences of Fatigue from Insufficient Sleep. Available from: https://www.ncbi.nlm.nih.gov/books/NBK384963/

20. Irish, L. A., Kline, C. E., Gunn, H. E., Buysse, D. J., & Hall, M. H. (2015). The Role of Sleep Hygiene in Promoting Public Health: A Review of Empirical Evidence. Sleep Medicine Reviews, 22, 23. https://doi.org/10.1016/j.smrv.2014.10.001

21. Patel PN, Horenstein MS, Zwibel H. Exercise Physiology. [Updated 2024 Oct 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482280/

22. Wender, C. L. A., Manninen, M., & O'Connor, P. J. (2022). The Effect of Chronic Exercise on Energy and Fatigue States: A Systematic Review and Meta-Analysis of Randomized Trials. Frontiers in psychology, 13, 907637. https://doi.org/10.3389/fpsyg.2022.907637

23. Herman, J. P., McKlveen, J. M., Ghosal, S., Kopp, B., Wulsin, A., Makinson, R., Scheimann, J., & Myers, B. (2016). Regulation of the Hypothalamic-Pituitary-Adrenocortical Stress Response. Comprehensive Physiology, 6(2), 603–621. https://doi.org/10.1002/cphy.c150015

24. Liao, L. Y., He, Y. F., Li, L., Meng, H., Dong, Y. M., Yi, F., & Xiao, P. G. (2018). A preliminary review of studies on adaptogens: comparison of their bioactivity in TCM with that of ginseng-like herbs used worldwide. Chinese medicine, 13, 57. https://doi.org/10.1186/s13020-018-0214-9

25. Panossian, A., & Wikman, G. (2010). Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress-Protective Activity. Pharmaceuticals (Basel, Switzerland), 3(1), 188–224. https://doi.org/10.3390/ph3010188

26. Lopresti, A. L., Smith, S. J., Malvi, H., & Kodgule, R. (2019). An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine, 98(37), e17186. https://doi.org/10.1097/MD.0000000000017186

27. Tinsley, G. M., Jagim, A. R., Potter, G. D. M., Garner, D., & Galpin, A. J. (2024). Rhodiola rosea as an adaptogen to enhance exercise performance: a review of the literature. The British journal of nutrition, 131(3), 461–473. https://doi.org/10.1017/S0007114523001988

28. Bach, H. V., Kim, J., Myung, S. K., & Cho, Y. A. (2016). Efficacy of Ginseng Supplements on Fatigue and Physical Performance: a Meta-analysis. Journal of Korean medical science, 31(12), 1879–1886. https://doi.org/10.3346/jkms.2016.31.12.1879

29. Zhang, G., Lu, B., Wang, E., Wang, W., Li, Z., Jiao, L., Li, H., & Wu, W. (2023). Panax ginseng improves physical recovery and energy utilization on chronic fatigue in rats through the PI3K/AKT/mTOR signalling pathway. Pharmaceutical biology, 61(1), 316–323. https://doi.org/10.1080/13880209.2023.2169719

30. Wauquier, F., Boutin-Wittrant, L., Pourtau, L., Gaudout, D., Moras, B., Vignault, A., Monchaux De Oliveira, C., Gabaston, J., Vaysse, C., Bertrand, K., Abrous, H., Capuron, L., Castanon, N., Vauzour, D., Roux, V., Macian, N., Pickering, G., & Wittrant, Y. (2022). Circulating Human Serum Metabolites Derived from the Intake of a Saffron Extract (Safr'InsideTM) Protect Neurons from Oxidative Stress: Consideration for Depressive Disorders. Nutrients, 14(7), 1511. https://doi.org/10.3390/nu14071511

31. Musazadeh, V., Zarezadeh, M., Faghfouri, A. H., Keramati, M., Ghoreishi, Z., & Farnam, A. (2021). Saffron, as an adjunct therapy, contributes to relieve depression symptoms: An umbrella meta-analysis. Pharmacological Research, 175, 105963. https://doi.org/10.1016/j.phrs.2021.105963

32. Calderón-Ospina, C. A., & Nava-Mesa, M. O. (2020). B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. CNS neuroscience & therapeutics, 26(1), 5–13. https://doi.org/10.1111/cns.13207

33. Tardy A-L, Pouteau E, Marquez D, Yilmaz C, Scholey A. Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence. Nutrients. 2020; 12(1):228. https://doi.org/10.3390/nu12010228

34. Schwalfenberg, G. K., & Genuis, S. J. (2017). The Importance of Magnesium in Clinical Healthcare. Scientifica, 2017, 4179326. https://doi.org/10.1155/2017/4179326

35. Al Alawi, A. M., Majoni, S. W., & Falhammar, H. (2018). Magnesium and Human Health: Perspectives and Research Directions. International journal of endocrinology, 2018, 9041694. https://doi.org/10.1155/2018/9041694

36. Yang, J., Li, Q., Feng, Y., & Zeng, Y. (2023). Iron Deficiency and Iron Deficiency Anemia: Potential Risk Factors in Bone Loss. International journal of molecular sciences, 24(8), 6891. https://doi.org/10.3390/ijms24086891

37. Silva, S. V. E., Gallia, M. C., Luz, J. R. D. D., Rezende, A. A., Bongiovanni, G. A., Araujo-Silva, G., & Almeida, M. D. G. (2022). Antioxidant Effect of Coenzyme Q10 in the Prevention of Oxidative Stress in Arsenic-Treated CHO-K1 Cells and Possible Participation of Zinc as a Pro-Oxidant Agent. Nutrients, 14(16), 3265. https://doi.org/10.3390/nu14163265

38. Mantle D, Hargreaves IP, Domingo JC, Castro-Marrero J. Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview. International Journal of Molecular Sciences. 2024; 25(1):574. https://doi.org/10.3390/ijms25010574

39. Calder P. C. (2010). Omega-3 fatty acids and inflammatory processes. Nutrients, 2(3), 355–374. https://doi.org/10.3390/nu2030355

40. Jannas-Vela, S., Espinosa, A., Candia, A. A., Flores-Opazo, M., Peñailillo, L., & Valenzuela, R. (2023). The Role of Omega-3 Polyunsaturated Fatty Acids and Their Lipid Mediators on Skeletal Muscle Regeneration: A Narrative Review. Nutrients, 15(4), 871. https://doi.org/10.3390/nu15040871

41. Taren, A. A., Gianaros, P. J., Greco, C. M., Lindsay, E. K., Fairgrieve, A., Brown, K. W., Rosen, R. K., Ferris, J. L., Julson, E., Marsland, A. L., Bursley, J. K., Ramsburg, J., & Creswell, J. D. (2015). Mindfulness meditation training alters stress-related amygdala resting state functional connectivity: a randomized controlled trial. Social cognitive and affective neuroscience, 10(12), 1758–1768. https://doi.org/10.1093/scan/nsv066

42. Keng, S. L., Smoski, M. J., & Robins, C. J. (2011). Effects of mindfulness on psychological health: a review of empirical studies. Clinical psychology review, 31(6), 1041–1056. https://doi.org/10.1016/j.cpr.2011.04.006

43. Turakitwanakan W, Mekseepralard C, Busarakumtragul P. Effects of mindfulness meditation on serum cortisol of medical students. J Med Assoc Thai. 2013 Jan;96 Suppl 1:S90-5. PMID: 23724462.

44. Aeon, B., Faber, A., & Panaccio, A. (2021). Does time management work? A meta-analysis. PloS one, 16(1), e0245066. https://doi.org/10.1371/journal.pone.0245066

45. Lyubykh, Zhanna & Gulseren, Duygu & Premji, Zahra & Wingate, Timothy & Deng, Connie & Bélanger, Lisa & Turner, Nick. (2022). Role of Work Breaks in Well-Being and Performance: A Systematic Review and Future Research Agenda. Journal of Occupational Health Psychology. 10.1037/ocp0000337.

46. Nwobodo, E. P., Strukcinskiene, B., Razbadauskas, A., Grigoliene, R., & Agostinis-Sobrinho, C. (2023). Stress Management in Healthcare Organizations: The Nigerian Context. Healthcare (Basel, Switzerland), 11(21), 2815. https://doi.org/10.3390/healthcare11212815