How energetic we feel can be difficult to quantify or compare. However, many people report low energy or fatigue. A 2022 article in the Independent states that “One in eight UK adults feel tired all the time, according to a YouGov survey. Another quarter feel tired “most of the time”, while a third reported feeling weary around “half of the time.”1 Therefore, it is clear many people feel they would like or need more energy.
Some may just consider energy as useful by allowing us to get more done, but it is much more important than that. Energy is a sign of vitality and wellbeing and if we feel tired it is likely that our cells are not functioning optimally. Nearly every, if not all, chronic disease may be exacerbated or even triggered by suboptimal energy production by our cells’ powerhouses, the mitochondria. Hence optimising energy production is an essential intervention for chronic disease and supporting energy levels can be vital for maintaining wellbeing and vitality.
An example of energy affecting wellbeing may be highlighted when considering depression. A suggestion by Dr Sarah Myhill is that depression is a symptom of fatigue, as a way of preserving energy as it makes us apathetic, unmotivated, and lethargic, hence the body deliberately depresses our energy levels to conserve it.2
Therefore, this blog looks at how energy is produced, what influences energy and how we can support energy production, particularly by supporting the mitochondria.
Energy production: How our bodies get energy
Energy production is reliant on a whole myriad of processes to all be working effectively to have optimal energy available to us.3
Firstly, energy needs to enter the cells; this is dependent on the foods we are consuming, how effective the digestive system is at absorbing nutrients, delivery of nutrients to cells via the cardiovascular system and uptake of sugar into the cells by insulin. Therefore, food choices, digestive health, cardiovascular health and insulin sensitivity are all factors which can affect energy availability.
- Once glucose (primary fuel source although body can also use ketones) has entered the cell it goes through glycolysis (breakdown of glucose); this produces a small amount of net energy as ATP as some initial energy expenditure is needed to initiate the process. Mainly it leads to the production of pyruvate and then acetyl CoA which can be further utilised for energy production by the mitochondria – nutrients including B2, B3 and B5 are essential for this. Glycolysis can occur in the absence of oxygen and therefore may also be known as anaerobic. Under bouts of intense exercise, the processes in the mitochondria become backed up due to reduced availability of oxygen and cannot produce energy quickly enough. This means that pyruvate is instead converted to lactic acid to allow for anaerobic respiration to continue, a cause of muscle fatigue and pain.
- Acetyl CoA then enters the Krebs cycle found within the mitochondria to produce some ATP as well as Nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH). Certain amino acids and B vitamins are essential for this process, hence adequate protein is necessary for optimal mitochondrial function.
- The NADH and FADH then enter the electron transport chain (ETC) to allow them to be further converted to ATP (energy). Nutrients including copper, iron and CoQ10 are fundamental to this process.
What influences energy production?
It can be seen from the above that many nutrients are required for energy production by the body and it is a complicated process involving multiple body systems.
Some considerations for boosting energy levels should be:
Bridge the Nutrition Gap – we discuss the importance of individual nutrients below. However, ensuring optimal intake of all nutrients as a base with a good quality multivitamin and mineral is a good way to ensure your cells have everything available to them to create energy.
Consider your hormones – low thyroid function, stress, reproductive disorders and poor blood sugar regulation can all affect energy production. For further information see our blog: Trophic support for cognitive disorders – which is also relevant for energy disorders.
Nutrient absorption and delivery – even if nutrient intake is optimal, these nutrients still need to be absorbed and then transported to the cell. Digestive and cardiovascular function are therefore essential.
Adequate sleep – this one is easier said than done. If you are not getting adequate sleep you are depleting your energy reserves, not allowing time to fully recover, increasing stress hormones and inflammation, all of which can affect energy levels. Practising good sleep hygiene is a good first start. See our blog Make better sleep your goal.4
Role of mitochondria in energy production
Mitochondrial dysfunction is a consistent factor in conditions associated with fatigue as well as in sub-optimal energy production. The mitochondria are the powerhouses of the cell and the site of the most efficient form of energy production, aerobic respiration.
Mitochondria possess their own DNA, which is much more susceptible to damage and oxidation due to the lack of protection by the nucleus that nuclear DNA benefits from. Although much of mitochondrial function is encoded in nuclear DNA, mitochondrial DNA plays an essential role in normal function.
The increased vulnerability to oxidative stress means that when oxidative damage risk is increased by stress, inflammation, and toxicity, and antioxidant systems are under pressure, the mitochondria can struggle to function effectively, meaning that energy production is reduced. The persistence of mitochondrial DNA damage ultimately leads to mutations in the mitochondrial genome and gives rise to further mitochondrial dysfunction, which induces and aggravates conditions of fatigue.3
This is coupled with the fact that mitochondria are one of, if not the most, common source of free radical production. Oxidative stress from free radicals is normal and, in moderate amounts, essential for mitochondrial function. However, when the mitochondria are damaged, the ETC (an essential aspect of energy production) become increasingly “leaky” which allows more electrons to “escape” causing further damage and less efficient energy production.4
During normal aerobic respiration, 2% of electrons leak out of the ETC. This transports electrons directly to oxygen and therefore leads to the creation of the superoxide free radical. It has been estimated that the steady-state concentration of superoxide (a potent free radical) in the mitochondrial matrix is 5-to-10- fold higher than in the cytosol.
Hence, adequate antioxidant systems are essential. The antioxidant systems, superoxide dismutase and glutathione, are vital in protecting and preserving the integrity and function of the mitochondria.
The term “mitophagy” was in use by 1998. Mitophagy is key in keeping the cell healthy. It promotes turnover of mitochondria and prevents accumulation of dysfunctional mitochondria, which can lead to cellular degeneration.
It is essential that if mitochondria are dysfunctional, they go through mitophagy, the process of breaking down and dismantling dying off mitochondria. This prevents increased reactive oxygen species created by “sick” mitochondria that are limping on, and allows for mitochondrial biogenesis, the production of new mitochondria. It’s almost a salvage operation. The balance between mitophagy and mitochondrial biogenesis occurs in healthy people and is known as mitochondrial homeostasis.
If mitochondrial homeostasis is impaired, there is an excess of inefficient mitochondria producing poor amounts of energy and increased oxidation, which is a major contributor to fatigue. Therefore, supporting mitochondrial homeostasis is important.5
Mitochondrial homeostasis is preserved by the fine co‐ordination between two opposing processes: generation of new mitochondria, by mitochondrial biogenesis, and the removal of damaged mitochondria, by mitophagy.6,7
Mitochondrial biogenesis induction is associated with activation of transcription factors and enzymes that act on mitochondrial genes and with the up‐regulation of local translation of mitochondrial proteins to stimulate the production of new mitochondria.
These include NRF2, SIRT, AMPK, PGC-1, and PPAR. Interestingly, most of these molecules are also associated with longevity and fat burning. Their production has been shown to be stimulated in response to several natural products, including5,8,9
Green Tea Extract
|Thai Black ginger
Many of the above nutrients can be supplemented but they can also be obtained in the diet. Eating a rainbow diet, providing a rich diversity of plant-based phytonutrients (especially polyphenols) can help obtain some of the above. Tangeritin can be found in citrus fruits, particularly sweet oranges, resveratrol in red grapes and berries as well as red wine, sulforaphane in dark leafy greens and brassica vegetables.
Cooking with potent spices such as turmeric and ginger as well as garlic can provide many benefits to mitochondrial biogenesis.
Lifestyle factors have also been shown to stimulate mitochondrial biogenesis and putting the body in a slight, reversible state of stress is beneficial for maintaining mitochondrial homeostasis. These lifestyle factors include:
- Caloric restriction
- Cold exposure
Fasting, in particular, has extensive supporting research for the stimulation of mitochondrial biogenesis6:
- Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) is a fasting-induced transcriptional coactivator that mediates mitochondrial biogenesis, activates when the body receives a signal that it needs more cellular energy, and increases in expression during fasting.5,8
- Nuclear factor (erythroid-derived) factor 2 (Nrf2) is a transcription factor that regulates ROS production by the mitochondria. Studies suggest that Nrf2 is associated with mitochondrial biogenesis and may be involved in mitochondrial quality control systems. A 2019 study evaluated the impact of Ramadan intermittent fasting on the expression of antioxidant genes, including Nrf2, and results suggested that fasting improved the expression of the antioxidant regulatory genes.10
Intermittent fasting – try to go for 12 hours (overnight) without eating, this significantly reduces insulin levels and therefore helps blood sugar regulation. I.e., do not eat between 7pm and 7am. If you can stretch this to 14 or 16 hours, it can be really beneficial. Other options are 5:2 (only consuming 500 calories on 2 days of the week). For further information see our blog Time restricted eating | Cytoplan blog with Jeannette Hyde
Nutrients that support chemical energy production by the mitochondria 3,11–13:
Thiamine (B1) – cofactor in the essential step which converts pyruvate into acetyl CoA.
Riboflavin (B2) – also known as FAD, accepts electrons and donates to the ETC to produce ATP (energy).
Niacin (B3) – also known as NADH (similar to FAD) accepts and donates electrons to the ETC to produce ATP.
Nicotinamide riboside (a form of vitamin B3 that functions as a precursor to NAD) – has shown similar benefits to caloric restriction and may support mitochondrial biogenesis. It is a rate limiting co-substrate for the family of sirtuin enzymes. Increasing levels of the co-substrate NAD increases the activity of these enzymes and oral supplementation with nicotinamide riboside has been shown to increase levels of NAD.13
Pantothenic Acid (B5) – carrier of Coenzyme A, essential for Acetyl CoA and therefore energy production.
CoQ10 (Ubiquinol) – utilised as a carrier in complex II of the ETC. CoQ10 also has antioxidant properties and is found in high concentrations in the heart and brain. It therefore plays an essential role in cognitive and cardiovascular function as well as in normal energy production, all of which are implicated in Chronic Fatigue Syndrome (CFS).
Alpha Lipoic Acid – a coenzyme of pyruvate dehydrogenase and a-ketoglutarate; enzymes responsible for reactions involved in the breakdown of fat and carbohydrate within the mitochondria.
Magnesium – binds to ATP and affects its structure, making energy more easily available.
All of the above nutrients are directly involved in metabolism reactions which occur in the mitochondria in order to produce energy. #
Any deficiencies of the above nutrients can affect the rate of energy production.
There are other nutrients that are not directly involved in the chemical pathways of metabolism but are important for energy production and maintaining mitochondrial function such as:
L-Carnitine – plays a vital role in fatty acid metabolism and transporting fatty acids into the mitochondria to be converted into energy. Again, a deficiency can lead to reduced energy production.
Omega 3 Fatty Acids – can be incorporated into the mitochondrial membrane, which aids fluidity of the membrane and therefore signalling. Omega 3 fatty acids are also very important for cell and mitochondrial membranes and hence their stability.
D-Ribose – may be useful to support ATP production by encouraging re-phosphorylation, particularly within muscle, including cardiac muscle. It is used effectively in chronic fatigue patients and can also improve exercise tolerance.14
Oxidative stress and antioxidants
We can also help to protect our mitochondria by ensuring that we are consuming adequate levels of antioxidants. The antioxidant of particular importance for the mitochondria is glutathione, which is our own intrinsic intracellular antioxidant. Although we are able to manufacture our own glutathione, when oxidative stress is in excess, it can become overwhelmed. Or, if nutrients that are required to manufacture it are deficient, this can lead to reduced levels. Nutrients that support the production of glutathione include.
Liposomal Glutathione – this bypasses degradation within the gut and is absorbed directly across the digestive lining and can cross the blood-brain barrier.
N-Acetyl Cysteine – regulates synthesis of and is an effective precursor to glutathione.
Alpha Lipoic Acid – has the ability to induce enzymes required for glutathione synthesis.
Selenium – constituent of glutathione.
Vitamin C – an antioxidant in its own right but also has the ability to regenerate glutathione. Vitamin C is also an essential nutrient for adrenal function. Adrenal dysfunction is considered to be a major driver of fatigue issues including CFS.
Other antioxidants have the ability to reduce oxidative stress by neutralising free radicles and could be considered to support mitochondrial function in doing so. These include carotenoids, flavonoids, vitamin E, vitamin A and zinc – this list is not exhaustive. You can ensure that you are obtaining good levels of antioxidants in the diet by:
- Eating a rainbow diet (different colours of fruit and vegetables contain differing phytonutrients which have antioxidant properties).
- Consuming herbs and spices including turmeric, garlic, and ginger.
- Including polyphenols – found in olives, 70%+ dark chocolate (1-2 squares) and small quantities of red wine.
- Consuming antioxidant containing teas such as green tea and rooibos.
It is also important to consider the way in which excess oxidative stress occurs and therefore reducing sources of oxidation can be useful. Factors that contribute to oxidative stress include:
- High stress levels
- High sugar diet
- Consumption of trans and hydrogenated fats
- Chemicals from household products, toiletries, and cosmetics
- Energy production is initially reliant of the availability of nutrients to the cell. Therefore diet, digestion, cardiovascular health, and insulin sensitivity are essential for the ability to produce energy.
- Energy production within the cell is reliant on many nutrients including B vitamins, CoQ10, omega 3 fatty acids, iron, copper, and magnesium. Therefore, ensuing optimal intake of all nutrients by bridging the nutrition gap with a good quality multivitamin and mineral is essential.
- Other factors which affect energy production include sleep, hormone regulation, stress and oxidative stress. Therefore, interventions to support these need to be considered.
- Mitochondrial homeostasis is preserved by the fine co‐ordination between two opposing processes: generation of new mitochondria, by mitochondrial biogenesis, and the removal of damaged mitochondria, by mitophagy. Supporting mitochondrial homeostasis is essential for preserving and supporting energy, particularly in patients with CFS.
- Mitochondrial biogenesis induction is associated with activation of transcription factors and enzymes that act on mitochondrial genes and with the up regulation of local translation of mitochondrial proteins to stimulate the production of new mitochondria. These include NRF2, SIRT, AMPK, PGC-1, and PPAR. These are stimulated by natural phytonutrients such as tangeretin, resveratrol, green tea, and spirulina. Additionally, lifestyle factors including caloric restriction, cold exposure, exercise, meditation and fasting.
- It is also important to investigate other factors that may be either driving mitochondrial dysfunction or causing energy depletion. These may include inflammation, adrenal dysfunction, stress, thyroid dysfunction, poor sleep, and depression.
All of our blogs are written by our team of expert Nutritional Therapists. If you have questions regarding the topics that have been raised, or any other health matters, please do contact them using the details below:
1. One in eight UK adults feel tired ‘all the time’, survey finds | The Independent. Accessed January 18, 2024. https://www.independent.co.uk/life-style/health-and-families/tired-all-the-time-yougov-survey-b1991348.html
2. Myhill Sarah RC. The Energy Equation.; 2020.
3. Bland J et al. Textbook of Functional Medicine.; 2008.
4. Make better sleep your goal – Cytoplan. Accessed January 18, 2024. https://blog.cytoplan.co.uk/make-better-sleep-your-goal/
5. Popov LD. Mitochondrial biogenesis: An update. J Cell Mol Med. 2020;24(9):4892.
6. Viloria MAD, Li Q, Lu W, et al. Effect of exercise training on cardiac mitochondrial respiration, biogenesis, dynamics, and mitophagy in ischemic heart disease. Front Cardiovasc Med. 2022;9.
7. Li W, He P, Huang Y, et al. Selective autophagy of intracellular organelles: recent research advances. Theranostics. 2021;11(1):222-256.
8. Storoschuk KL, Lesiuk D, Nuttall J, et al. Impact of fasting on the AMPK and PGC-1α axis in rodent and human skeletal muscle: A systematic review. Metabolism. 2023;152:155768.
9. Qin J, Li Y, Wang K. Propofol induces impairment of mitochondrial biogenesis through inhibiting the expression of peroxisome proliferator–activated receptor-γ coactivator-1α. J Cell Biochem. 2019;120(10):18288-18297.
10. Madkour MI, T. El-Serafi A, Jahrami HA, et al. Ramadan diurnal intermittent fasting modulates SOD2, TFAM, Nrf2, and sirtuins (SIRT1, SIRT3) gene expressions in subjects with overweight and obesity. Diabetes Res Clin Pract. 2019;155.
11. Tardy AL, 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).
12. Depeint F, Bruce WR, Shangari N, Mehta R, O’Brien PJ. Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism. Chem Biol Interact. 2006;163(1-2):94-112.
13. Belenky P, Racette FG, Bogan KL, McClure JM, Smith JS, Brenner C. Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell. 2007;129(3):473-484.
14. Mahoney DE, Hiebert JB, Thimmesch A, et al. Understanding D-Ribose and Mitochondrial Function. Adv Biosci Clin Med. 2018;6(1):1.
Last updated on 31st January 2024 by cytoffice