Mitochondria

The functionality of energy – Ian Craig

Rather than thinking of energy in terms of macronutrient contributions, let’s understand more about how it is made. Ian Craig unearths three important areas of functional energy provision.

Energy is the cornerstone of every good athlete’s armoury: having vibrant energy means coping with tough training sessions and racing with passion; to be without high energy levels is akin to a career of missed opportunities and unfulfilled goals. In the perception of many sports people, energy has become synonymous with carbohydrate and fat consumption plus biochemical transformation, but macronutrients only convey a small part of the energy story. Production of the chemical form of energy, adenosine triphosphate (ATP), is a very intricate, whole-body process with many parts to it.

Energy production is influenced by our digestion, detoxification, immune system, our hormones and nerves, the active muscles themselves and also, as demonstrated by our sports psychologist colleagues, our mind and spirit. Genetics also play a massive role in all things physical and recent discoveries have revealed why some athletes simply have an energetic advantage before their toe touches the line.

Only focussing on our fuel needs (e.g. carbohydrates) is akin to simply putting petrol in your car. In order for it to run fluidly and efficiently, you need to check that it has enough fresh oil, that the gaskets are sealing properly and that your spark plugs are igniting vibrantly. These maintenance steps are done according to the car’s make and model (our genes). This makes your dietary needs a bit more complex than simply ensuring adequate fuel for energy, but the effort will be worthwhile when your performances take on a new dimension.

Let’s get into more detail with regard to the body systems that influence our energy supplies:

Circulation  the transport of energy

Early exercise physiology research established that with appropriate exercise training, some individuals could greatly enhance the capacity of their heart and cardiovascular system. For example, whereas the size of a normal man’s heart is around 700 to 800ml, some endurance athletes have been shown to double this volume (1), corresponding with a huge upward shift in the heart’s cardiac output. This, in turn, would mean more oxygen getting to our active tissues and the potential of more aerobically-produced ATP for energy.

We now understand that some athletes can achieve these cardiovascular adaptations more easily than others. Certain genes have been identified that are associated with vascular growth and control, inferring potential endurance advantages. For example, the Angiotensin Converting Enzyme (ACE) gene, known for its involvement in blood pressure control, is highly related to success in endurance or power sports depending on an individual’s genotype (2). Additionally, Vascular Endothelial Growth Factor (VEGF), involved in the growth of new blood vessels, has been related to baseline VO2max levels and VO2max response to training depending on the genotype possessed (3,4).

We can’t do too much about our genetic code except to accept our strengths and weaknesses and to train and live according to them. But, it is very possible to support our unique cardiovascular nutritional needs, increase or decrease the expression of certain genes, and aid the degree of adaptations that can be made to training for energy production. Athletes, especially endurance athletes who complete high weekly volumes of training, put their cardiovascular system under great strain. This is an essential part of boosting heart size and vascular supply to active muscles, but unless the essential building blocks of the new vascular tissue are supplied, the adaptations won’t happen so quickly.

Let’s examine another model of vascular strain for a moment: cardiovascular disease. According to an extensive literature review (5) that assessed the optimal diets for the prevention of coronary disease, the following dietary steps should be made: increase the consumption of omega-3 fatty acids from fish, fish oil supplements and seeds; consume a diet high in fruit, vegetables, nuts, whole grains and low in refined grain products. In particular, EPA and DHA oils in fish have been shown to improve the function of blood vessel walls, along with improving insulin sensitivity, decreasing inflammation and other cardio-supportive functions (6). Although a young athlete may not relate to problems with cardiovascular disease, it should be motivating to think about the vascular adaptations that could occur by consuming these foods, allowing for optimal energy transportation.

Mitochondria  the powerhouses of the cell

Collectively, all the cells in our body are thought to contain around 100,000 trillion mitochondria, and since they convert fuel into ATP energy, they play an immensely important role in energy provision to every single body system. Mitochondria are the direct descendants of α-proteobacteria, and because of their ancient bacterial origin, they have their own genome and a capacity for auto-replication. Given this bacterial connection, it will be fascinating to see what information will be unearthed by future research with regard to the relationship between the health of the human microbiota and mitochondrial genetics (7).

The mitochondrial density is highest in cells with the most aerobic activity: around 40 per cent of heart cell volume is made up of mitochondria. They are also extremely numerous in active muscle cells and are supremely important for aerobic exercise capacity. A very interesting study showed this clearly (8): a group of rats were divided into those with the strongest endurance and those with the weakest endurance abilities (by seeing how long they could run at a certain speed). The rats were then allowed to breed within their chosen group, and the offspring were again tested for endurance abilities and split again by talent.

This pattern was repeated for 11 generations until the researchers had a group of super rats and a group of couch potato rats. At this stage, the high-endurance rats could run 3 ½ times longer than the low-endurance group. What was most interesting about this experiment was that even in an untrained state, mitochondrial content was much higher in the high-endurance rat muscles, and the proteins that are responsible for stimulating new mitochondria production were also significantly higher in the high-endurance group. Also, the low-endurance rats displayed many risk factors for heart disease and diabetes, including elevated blood pressure, blood fats and dysregulation of blood sugars.

As noted, mitochondria influence the health of every body system. Therefore, insufficiency or dysfunction of mitochondria leads to decrements in physical performance and energy and has been linked to chronic fatigue, fibromyalgia, cardiomyopathy, various neuromuscular symptoms, and possibly even ageing (9).

Genetically, a family of nuclear receptors called PPAR (peroxisome proliferator-activated receptor) have been identified that are associated with the growth of new mitochondria (biogenesis). Knowledge of this information can infer potential advantages to endurance athletic performance in some individuals. Let’s focus on one of them: PGC-1α is considered by some to be the master regulator of mitochondrial generation (10). Additionally, this gene is involved in fat metabolism, forming fat cells, using glucose for energy, thermogenesis, new blood vessel growth and muscle fibre type conversion towards slow-twitch fibres. It is expressed in tissues with high energy demands and is abundant in mitochondria.

Research has shown that a certain PGC-1α genotype (GG) has been strongly associated with elite endurance performance (11,12,13) and superior response to exercise training, resulting in better improvements in insulin sensitivity and lactate threshold (14).

This information would be useless without something you can do to support your genes. Regardless of our genotype, a number of activities and nutrients have been shown to up-regulate the PGC-1α gene. As shown in Figure 1, exercise itself increases the expression of PGC-1α function, which makes sense so that the body can adapt to harder training loads. Nutritionally, the antioxidant resveratrol (the youthful nutrient in red wine linked to the anti-ageing gene SIRT1) plus lipoic acid, an important mitochondrial antioxidant, have been shown to stimulate PGC-1α function. Nitric oxide (NO), an important vascular dilator, also bolsters PGC-1α activity. Supplementing the amino acid l-arginine will rapidly increase NO, which has been one way to manage vascular occlusion problems like angina. However, what is much more interesting is recent research into whole foods high in nitrates.

A particular study demonstrated that short-term increases in dietary nitrates (found in green leafy vegetables and beetroot juice) could boost muscle efficiency during exercise because of increased mitochondrial output (15). In the study, there was actually a 19 per cent increase in the amount of ATP produced per unit of oxygen used, which corresponded to a lower consumption of oxygen while riding an exercise bike at a certain intensity. Independent research additionally showed that when half a litre of beetroot juice was consumed daily for six days, the running economy improved, and endurance time to exhaustion was extended by 16 per cent.

Mitochondrial biogenesis is also triggered by environmental stresses such as exercise, cold exposure, caloric restriction and oxidative stress, cell division, renewal and differentiation, and to this end, AMPK (5’ adenosine monophosphate-activated protein kinase) is of particular interest. AMPK is activated by stressors that decrease cellular energy, including exercise, hypoxia and hypoglycaemia. In an effort to restore cellular energy, the action of AMPK is to promote mitochondrial biogenesis, fatty acid oxidation, glycolysis and glucose uptake, resulting in an increased insulin sensitivity. Foods that activate AMPK include resveratrol (16), catechins (17), capsaicin (18) and curcumin (19).

energy

 

Figure 1 – mitochondrial biogenesis (adapted from Evans (20))

Energy production – inside the mitochondria

Again, it is important to look beyond our genetic make-up and understand how to support these energy systems nutritionally. Looking inside the mitochondria, you’ll find an array of biochemical pathways rote-learned by every nutrition and physiology student. Figure 2 shows these as the breakdown fuels (carbs and fats), the infamous Krebs cycle, which generates electrons, and the electron transfer chain, which produces ATP molecules in an oxygen-rich environment.

These pathways have been described in great detail in almost every exercise physiology book written. However, our focus is not so much the biochemical pathways themselves, but the micronutrients required for these processes to proceed efficiently; they are not described in most textbooks. Most people have heard that B-vitamins are important for energy, but not why? Looking at Figure 2, you’ll understand that they are needed for the transfer of carbohydrate, fat and protein break-down products into the Krebs cycle and for the actual circulation of the Krebs cycle. Lipoic acid is also required and is a popular supplement for mitochondrial energy. Also worthy of mention are carnitine, needed for the transfer of fatty acids into the Krebs cycle, and coenzyme Q10 for the completion of the electron transfer chain.

Another nutrient that’s gaining more attention these days is the sugar D-ribose. It is produced during the breakdown of carbohydrates and directly supports the production of the genetic material, DNA and RNA. It also plays a part in the synthesis of fatty acids, the production of anabolic hormones such as cortisol and testosterone, and the action of our anti-oxidant enzymes. A multi-centre trial (21), which examined 257 patients with chronic fatigue and fibromyalgia (conditions often observed in over-achieving athletes), revealed that a daily dose of D-ribose resulted in an average increase in energy of 61 per cent after only 3-weeks. The researchers also found improved sleep, cognitive function and overall function, and decreased perceived pain.

energy

 

Figure 2 – The Krebs cycle (adapted from Lord & Bralley (22))

Conclusions

As you can see from this short account, energy is an incredibly complex phenomenon even by staying within the physiological realm. It can be partly explained by what we eat, but only if we look beyond our food’s typical gram value analysis. Assuming adequate macronutrient flux through the Krebs cycle, energy is strongly reliant on biochemical co-factor needs plus phytonutrient contributions to the cell that work through means of genetic expression via mechanisms that are slowly but surely being elicited by science. The next decade of science is going to be fascinating to find out what other biochemical processes we thought we understood completely, but actually don’t.

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  4. Prior S et al (2006). DNA sequence variation in the promoter region of the VEGF gene impacts VEGF gene expression and maximal oxygen consumption. Am J Physiol Heart Circ Physiol. 290(5):H1848-1855.
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  11. Eynon N et al (2009). Is there an interaction between PPARD T294C and PPARGC1A Gly482Ser polymorphisms and human endurance performance? Exp Physiol. 94(11):1147-1152.
  12. Eynon N et al (2010). Do PPARGC1A and PPARalpha polymorphisms influence sprint or endurance phenotypes? Scand J Med Sci Sports. 20(1):e145-e150.
  13. Lucia A et al (2005). PPARGC1A genotype (Gly482Ser) predicts exceptional endurance capacity in European men. J Appl Physiol. 99(1):344-348.
  14. Stefan N et al (2007). Genetic variations in PPARD and PPARGC1A determine mitochondrial function and change in aerobic physical fitness and insulin sensitivity during lifestyle intervention. J Clin Endocrinol Metab. 92(5):1827-1833.
  15. LarsenF (2011). Dietary inorganic nitrate improves mitochondrial efficiency in humans. Cell Metab. 13(2):149-159.
  16. Do et al (2012). Resveratrol ameliorates diabetes-related metabolic changes via activation of AMP-activated protein kinase and its downstream targets in db/db mice. Molecular Nutrition & Food Research. 56(8):1282-1291.
  17. Ali F et al (2013). Molecular mechanisms underlying the potential antiobesity-related diseases effect of cocoa polyphenols. Molecular Nutrition & Food Research. 57(6):974-985.
  18. Kim J et al (2010). Curcumin stimulates glucose uptake through AMPK-p38 MAPK pathways in L6 myotube cells. Journal of Cellular Physiology. 223(3):771-778.
  19. Kim J et al (2013). Capsaicin stimulates glucose uptake in C2C12 muscle cells via the reactive oxygen species (ROS)/AMPK/p38 MAPK pathway.Biochemical and biophysical research communications.439(1):66-70.
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  21. Teitelbaum J et al (2012). Effective treatment of fibromyalgia and chronic fatigue syndrome with D-ribose – a multicenter study.The Open Pain Journal. 5:32-37.
  22. Lord S & Bralley J (2008). Laboratory Evaluations for Integrative and Functional Medicine. Metametrix Institute.

Ian Craig MSc DipCNE BANT Fellow INLPTA is the founder of the Centre for Integrative Sports Nutrition (CISN) and course leader of their online postgraduate level courses. He is an experienced exercise physiologist, nutritional therapist, NLP practitioner, and an endurance coach. Clinically, within a team dynamic, Ian works with sporting individuals and complex health cases at his Scottish home, and online. Additionally, Ian co-authored the Struik Lifestyle book Wholesome Nutrition with his natural chef wife Rachel Jesson, and the Routledge textbook Integrative Sport and Exercise Nutrition with Professor Justin Roberts.

LinkedIn: /ian-craig-nutrition

Twitter: @ian_nutrition

Specialty module: Harnessing Mitochondrial Energy