Mitochondrial Support: The Key to Endless Energy

by Carolyn Pierini, CLS (ASCP), CNC

Mitochondria are the generators of the cellular, aerobic energy that powers every fundamental need for reproduction and survival. This energy takes form in a molecule called adenosine-5’- triphosphate or ATP. A dynamic relationship exists between health and the efficiency of the mitochondria.

In his book Bursting With Energy, Frank Shallenberger, MD, a popular physician and anti-aging specialist, describes aging as not just the inevitable consequence of celebrating birthdays, but is defined medically as a decrease in the ability of the body to function efficiently. He asserts that all existing theories of aging are really secondary to one primary unifying explanation: a decrease in cellular ATP production in the mitochondria. This lack of ability to generate adequate energy helps explain why some people age more rapidly than others.¹

The interior of a living cell contains many components, or organelles; however, none are more important than the mitochondria because without an energy source the cell will die. We need to eat to obtain the potential energy stored in food to create a useable fuel for generating ATP. We also need to breathe because oxygen performs the final step in creating these high-energy molecules, which drive the biochemical reactions of metabolic function. The healthier we are, especially in terms of ideal weight, the better we are equipped to produce energy and the more energy we can produce, the healthier we are. It’s the classic case of the “rich get richer” in terms of metabolism. And although we are at the mercy of our genetic inheritance, we have the ability to adopt a lifestyle that favors the best expression of our genes (epigenetic science) for supporting an optimal supply of ATP. This discussion is aimed at highlighting several important aspects of energy production and how to improve energy levels.

Cellular Powerhouses

A typical cell provides many areas for scientific study. Especially popular are the nucleus and DNA, cell membranes, receptors and proteomics. Lately, the mitochondria are getting more attention due to emerging concepts about their regulation and function, the most important of which is ATP production. The details of mitochondrial function are very complex but in order to better understand how we can feel better and slow aging, a brief discussion is necessary.

Along with other organelles, the mitochondria are found in the cytoplasm of all cells. There are thousands of mitochondrion in metabolically active cells of tissues such as skeletal muscle, heart, brain, liver and kidney, occupying up to 40 percent of the cytoplasm, while blood cells and other cells such as skin contain less.² The brain appears to be the most metabolically active tissue, responsible for 20 percent of energy expenditure.³

The mitochondria contain their own DNA and different compartments where the citric acid cycle (Krebs cycle) and the electron transport chain (oxidative phosphorylation) operate to manufacture the ATP. Any interference in the energy process such as “uncoupling” in the transport of electrons will block the formation of ATP. Carbon monoxide is an example of an “un-coupler” that can cause death when enough energy production is blocked. Furthermore, conditions that decrease available oxygen to the cell will negatively impact energy production. Oxygen is the final acceptor of the transferred electrons that pump out ATP molecules, forming water but also giving rise to reactive oxygen species (ROS) or free radicals as a consequence of the biochemical reactions. The mitochondria happen to be the premier source of ROS in the body making them particularly vulnerable to free radical attack.⁴ Oxidative stress develops if the level of ROS increases and exceeds neutralization by antioxidants.^5-6 You may recall that oxidative stress is associated with inflammation imbalance, a key factor in long-term health maintenance.

Being overweight can impact health in a variety of ways. There may be many contributors to modern weight gain but an underlying cause is diminished energy production. As it relates to the inability to properly use fat as an energy source, excess weight gain stands as the most obvious disorder of energy production. Low energy and weight gain contribute to each other in a vicious cycle initiated by insulin imbalances. Except for brain cells, all other cells prefer to burn fat for energy because it is more efficient and produces less acidic waste than carbohydrates.¹ Excess carbohydrate consumption makes glucose readily available for energy without the need for the release of stored fat. Poor fat utilization leads to decreased energy and mitochondrial function. It forces the mitochondria to use glucose as an energy source resulting eventually in insulin and glucose (blood sugar) imbalances that lead to energy deficits.

Toxins Target the Mitochondria

In addition to diet (i.e. high carbohydrate) and lifestyle (i.e. sedentary), insulin function may also be affected by exposure from toxic environmental pollutants. Many toxins are known hormone disruptors of metabolism and invasive disruptors of the energy-making machinery in the mitochondrion. These toxins are capable of crossing the placenta, contributing to negative metabolic, epigenetic effects in the unborn through prenatal exposure.

The mitochondria are targets for environmental toxins such as pesticides, dioxins, PCBs, heavy metals such as mercury and other persistent organic pollutants (POPs). These toxins recirculate and accumulate in the body, moving through tissues, until they meet up with the cell’s mitochondria. Once inside the mitochondria they can interfere with the delivery of fuel or damage areas of the mitochondria such as the membranes, the electron transport chain, and the mitochondrial DNA, which lacks the histone protection of nuclear DNA. As mitochondrial function is impaired, ROS levels escalate, risking further damage to proteins, enzymes and the DNA.⁷

An example can be seen with the reduced activity of the electron transport chain in the brain cells of people with suboptimal cognitive function associated with oxidative damage.⁸ As mitochondria are impaired or destroyed, energy potential is lost. When this happens, there is less available energy to support detoxification and the body’s toxic load increases.⁹

The result is more disruption to energy production and another vicious cycle set into motion.

Toxin exposure today is at an all time high. Efficient detoxification is dependent on maintaining levels of the particular nutrients necessary to support the detox pathways. This is why daily detoxification support is considered a modern necessity. Toxicity is a serious problem for everybody but particularly the aging or overweight individual who is already experiencing a decline in energy production.

Mitochondria and Exercise

Any discussion of mitochondrial function, no matter how brief, should include the topic of physical exercise. Studies show that regular exercise provides countless benefits on many levels influencing inflammation and longevity.^10-11 Most people recognize that exercise improves energy and is beneficial to health. What is not so common knowledge is that the number of mitochondria in our cells is not fixed—you can actually make more of them!

The developing science of mitochondrial biogenesis or synthesis is not fully understood, but one key finding is that the best way to make more of these powerful little energy factories is through exercise.^12-15 People who exercise regularly understand this because they’ve experienced the energy surge. An increase in the overall sense of well-being and stamina is what motivates them to keep up the effort. The work that skeletal muscles engage in during exercise creates positive long-term cellular adaptations.^15-16 The primary adaptation is the increase in mitochondria in the muscle cell fiber which can be observed under a microscope.^14-15 Exercise-related messengers activate the master regulator of mitochondrial biogenesis which is PGC-1a (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) a transcription factor that binds to DNA for the synthesis of specific proteins including those used to make new mitochondria. One of the messenger molecules induced by exercise is nitric oxide (NO). One of nitric oxide’s functions is to increase blood flow of oxygen and nutrient substrate to the contracting muscle through dilation of blood vessels. Many of the regulatory tasks in the cell mediated by NO involve the mitochondria and are linked to mitochondrial biogenesis.^2,17-19 NO levels can be enhanced through the use of Neo40® Daily, a cutting-edge new supplement. (Please see the article about nitric oxide in this newsletter).

Besides exercise, the red wine polyphenol, resveratrol, has been exceptionally well-studied for its ability to mimic the effects of caloric restriction in up-regulating the pro-longevity gene, sirtuin-1 (SIRT-1). Among its many responsibilities, SIRT-1 activates PGC1a for increased mitochondrial biogenesis.^20-21 Resveratrol has additional health benefits including activation of NO, which, as noted above, increases PGC1a activity. In creating an effect similar to exercise on PGC1a activation, resveratrol may be considered an exercise mimic. Other nutrients such as lipoic acid, biotin and the branched chain amino acids (valine, leucine and isoleucine) are also being studied for their effects on PGC1a activation.

Although there is no substitute for all the benefits of exercise, supplements may help us achieve at least one major benefit — mitochondrial biogenesis!

In summary:

1) Reduce toxin exposures and clean up the mitochondrial interior and the rest of the body from environmental pollutants with the detoxification support team of Detox Complex and AL-CoFactors™. Because insulin imbalances and overweight are linked to a sluggish flow of liver bile, the shuttle for toxin elimination, the product known as Gallbladder Formula may be added for extra detoxification.

2) Improve glucose and fat metabolism to better fuel the mitochondria by reversing insulin imbalance and its effects through diet, lifestyle and metabolic nutrient support.

3) Increase support for the production of more mitochondria through stimulation of PGC1a by exercise and the use of supplements such as Neo40 Daily and Resveratrol Plus, which contains resveratrol and pterostilbene. Combining the quick-acting resveratrol and the longer-acting pterostilbene offers a higher level of health support than using either one of these on their own.

There might be a small number of people in the population today who can honestly say they have all the energy they want or need. In fact, caffeine is looking more like a substance-of-abuse in response to the nation’s “energy crisis.” But how many people who seek out energy drinks every few hours ever consider improving the function of their mitochondria when they feel a power drain? The eventual consequence of “squeezing the turnip” with this popular practice may lead, ironically, to systemic exhaustion.

Conclusion

Mitochondrial function is crucial for overall health and longevity and even if its capacity has declined due to factors such as age, toxicity or weight gain, we can take important steps to help increase energy production. A satisfying, natural food diet that is lower in calories and higher in nutrients, adequate sleep, exercise, adrenal stress reduction and the suggestions noted in this article can help achieve better energy. We are fortunate that science has and will continue to identify compounds in nature to create nutritional supplement approaches for stimulating mitochondrial production and function. The result contributes to: 1) Improved energy levels affecting mood and overall performance;. 2) Reduction of oxidative stress from ROS; 3) Decreased age-related decline; 4) Improved cognition and metabolic function; 5) Healthy levels of body fat and 6) Increased lean muscle.

References

1. Shallenberger F. Bursting with Energy. Laguna Beach: Basic Health, 2007, pg 33-41, 79-85.

2. Nisoli E, Carruba MO. Nitric oxide and mitochondrial biogenesis. J Cell. Sci 2006;119:2855-62.

3. Muller MJ, Bosy-Westphal A, et al. Metabolically active components of fat-free mass and resting energy expenditure in humans: recent lessons from imaging technologies. Obes Rev. 2002;23:795-807.

4. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA. 1993;90:7915-22.

5. Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120:483-495.

6. Conley KE, Marcinek DJ, Villarin J. Mitochondrial dysfunction and age. Curr Opin Clin Nutr Metab Care. 2007;10:688-692.

7. Aliev G, Li Y, Palacios HH, Obrenovich ME. Oxidative Stress Induced Mitochondrial DNA Deletion as a Hallmark for the Drug Development in the Context of the Cardiovascular Diseases. Recent Pat Cardiovasc Drug Discov. 2011 Aug 25. Published Online Ahead of Print.

8. Sullivan PG, Brown MR. Mitochondrial aging and dysfunction in Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29:407-410.

9. [No authors listed] [Regulation of the mitochondrial ATP-sensitive potassium channel in rat uterus cells by ROS]. [Article in Ukrainian]. Ukr Biokhim Zh. 2011 May-Jun;83(3):48-57.

10. Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature. 2008;454:463-469.

11. Metsios G, Stavropoulos-Kalinoglou A, et al. Vascular Function and Inflammation in Rheumatoid Arthritis: the Role of Physical Activity. Cardiovasc Med J. 2010;4:89-96.

12. Pilegaard H, Saltin B, et al. Exercise induces transient transcriptional activation of the PGC-1a gene in human skeletal muscle. J Physiol. 2003;546:851-858.

13. Baar K, Wende AR, et al. Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1a. FASEB J. 2002;16:1879-86.

14. Reznick RM, Shulman GI. The role of AMP-activated protein kinase in mitochondrial biogenesis. J Physiol. 2006;574:33-39.

15. Coffey VG, Hawly JA. The molecular basis of training adaptation. Sports Med. 2007;37:737-763.

16. Rockl KS, Witczzak CA, et al. Signaling mechanisms in skeletal muscle: acute responses and chronic adaptations to exercise. IUBMB Life. 2008;60:145-153.

17. Nisoli E, Falcone S, et al. Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science. 2003; 299:896-899.

18. Nisoli E, Falcone S, et al. Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals. Proc Natl Acad Sci USA. 2004;101:16507-16512.

19. Clementi E, Nisoli E. Nitric oxide and mitochondria biogenesis: a key to long-term regulation of cellular metabolism. Comp Biochem Physiol A Mol Integr Physiol. 2005;142:102-110.

20. Lagouge M, Argmann C, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006;127:1109-1122.

21. Sakamoto K. Silencing metabolic disorders by novel SIRT1 activators. Cell Metab. 2007;6:247-249.