We all want to live a long and happy life. This means staying healthy and feeling fit. It’s not that simple. Conventional health care treats you when you are ill, but it doesn’t cover keeping you energetic and agile. That’s all about how you take care of yourself!
As we age, we desire an active life. However, you will probably observe many people who have chronic diseases such as diabetes, heart disease, cancer, cognitive decline, or autoimmune disorders. Most of those degenerative diseases are not cured by the current system of medicine, which is about symptom relief. Unfortunately, most conditions will continue to deteriorate, depriving us of a happy, active long life. As a result, there is growing interest in discovering new ways to stay healthy, prevent and even cure those diseases in conjunction with conventional approaches.
In 2014 the work of Dr Wahls, neurologist and author of The Wahls Protocol, showed me for the first time an innovative, effective treatment based on epigenetic principles. She proved and validated that providing the essential nutrients to affected brain cells lead to restoration of cell function. It resulted in changing the course of a degenerative disease by repairing the biochemistry of the cells.
The revolutionary field of epigenetics reveals that our DNA is not a one road destiny but just a map where we can choose one of the better routes. After two decades of research it is no longer a vague concept. It is all on Pubmed. Only if you don’t know it, you don’t find it. For me it is very inspiring to know that I can actually do something myself to achieve a healthy future or can “biohack” a course of an onsetting degenerative disease.
There is one requirement; you need to understand the processes happening in your cells. That’s why we have chosen to develop this website.
This is an introduction to cellular processes as a starting point for effective health interventions, beginning with the explanation of cellular oxidative stress and the importance of reducing it. You will conclude that optimal mitochondrial function is the key to good health.
We believe the following information will serve as “food for thought” and a call for action.
Tessa Bergman, Chief Editor
A degenerative disease is a complex melding of genetic and epigenetic factors. Fortunately for us all, in many cases epigenetic factors will determine whether or not the gene will express a degenerative disease.
When you understand what your body actually needs to function and heal, you can start making wise decisions about how to keep your body going.
Most people are familiar with antioxidants and take them because they believe they will improve their health by reducing oxidative stress. Aging and roughly 200 diseases are directly linked to the process of oxidative stress. Our body fights oxidative stress by producing its own antioxidant enzymes, but as we grow older our bodies produce more free radicals and fewer antioxidant enzymes to defeat the progress of aging and disease. The following is an explanation of what oxidative stress* is and, even more importantly, we will offer you an opportunity to explore solutions.
WHAT IS OXIDATIVE STRESS?
Our cells need oxygen to create energy (ATP) from digested food compounds. This controlled metabolic process occurs in all our cells but mainly in the mitochondria. Unfortunately, it also creates harmful byproducts such as unstable free radicals and reactive oxygen species (ROS)**. To achieve stability, these byproducts get involved in a domino-like chain reaction that is destructive for the cells. Therefore, the cells have a built-in cellular defense and repair mechanisms in place to fight the free radical attacks, avoiding cellular damage and dysfunction. Antioxidants play an important role in the defense against oxidative stress. Essentially, oxidative stress is an imbalance between the presence of harmful by-products and the ability of the defense mechanism to scavenge enough of the free radicals or to repair the damage.
There are many factors contributing to oxidative stress: aging, diet, diseases, intensive exercise, pollution and more.”
* The scientific content of this website is simplified. For more in depth information we refer to the publications listed as a reference list.
We will use the words “free radicals” as a synonym for all the harmful products involved in the process of oxidative stress.
** ROS are also around us in the environment in the form of sunlight, air pollution, cigarette smoke, poor diet, and many other sources.
REFERENCES 1. Hybertson BM, et al. Role of diet in prostate cancer: the epigenetic link. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. JM. Mol Aspects Med. 2011;32(4-6):234-246. 2. Brunet A, et al. Epigenetics of Aging and Aging-related Disease. J Gerontol A Biol Sci Med Sci. 2014;69(1):S17–S20. 3. D’Aquila P, et al. Mitochondria in health, aging and diseases: the epigenetic perspective. Biogerontology. 2015;16(5):569-585. 4. Labbé DP, et al. Role of diet in prostate cancer: the epigenetic link. Oncogene. 2015;34(36):4683-4691. 5. Guzik TJ, et al. Epigenetics and Immunometabolism in Diabetes and Aging. Antioxid Redox Signal. 2017;doi:10.1089/ars.2017.7299 (Epub ahead of print). 6. Poljsak B. Strategies for Reducing or Preventing the Generation of Oxidative Stress. Oxidative Medicine and Cellular Longevity. vol. 2011, Article ID 194586, 15 pages, 2011. doi:10.1155/2011/194586. 7. Egea J, et al. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS). Redox Biol. 2017;13:94–162.
SOURCE Gelpi RJ et al. Biochemistry of oxidative stress: Physiopathology and clinical aspects. Springer International Publishing Switzerland 2016. ISBN 978-3-319-45864-9.
Mitochondria – the key to a good health
Mitochondria are tiny organelles in our body cells. Red blood cells and skin cells have very few to none, while most other cells have 1,000 – 2,000 of them.
In order for your organs to function properly, they require energy; and that energy is produced by the mitochondria.
To produce energy, your mitochondria require oxygen from the air you breathe and fat and glucose from the food you eat. These two processes – breathing and eating – are coupled together in a process called oxidative phosphorylation. That’s what the mitochondria use to generate energy in the form of ATP. ATP is the carrier of energy throughout your body.
Since mitochondrial function is at the very heart of everything that occurs in your body, optimizing mitochondrial function – and preventing mitochondrial dysfunction by making sure you get the right nutrients and precursors your mitochondria need – is extremely important for health and disease prevention.
However, that process also produces by-products such as free radicals and reactive oxygen species (ROS). These are not only damaging to your cells, but also to your mitochondrial DNA, which is effecting the nuclear DNA. These oxygen free radicals attack the lipids in your cell membranes, protein receptors, enzymes, and DNA. They can also prematurely kill your mitochondria.
Some free radicals are actually good and your body requires them to regulate cellular function, but problems develop when you have excessive free radical production. Your cells age due to the damaging aspects of the free radicals and ROS, and you become prone to disease.
How quickly your body ages depends largely on how well your mitochondria work and how well the damage can be minimized by optimization of your lifestyle: balanced nutrition, enough physical activity, avoiding toxins, and managing stress.
There are two possible solutions to this problem:
- Improve your cellular defense systems – increase antioxidant enzymes and antioxidants
- Reduce mitochondrial free radical production – reduce oxidative stress
Optimizing Mitochondrial Function
As mentioned above, you can optimize your mitochondrial function by reducing the oxidative stress level. Too high concentrations of ROS and free radicals would otherwise damage the mitochondria. An effective strategy is to increase the amount of antioxidant enzymes and antioxidants by facilitating the Nrf2 pathway.
For an optimal function the mitochondria also need specific nutrients. The following nutrients have been recognized as beneficial for your mitochondrial function:
- CoQ10 or ubiquinol (the reduced form)
- L-Carnitine, which shuttles fatty acids to the mitochondria
- D-ribose, which is raw material for ATP molecule
- Omega-3 fatty acids
- All B vitamins, including riboflavin, thiamine, and B6
- Alpha-lipoic acid (ALA)
Aging is inevitable, but you have enormous control over the way you age, by keeping your mitochondria in good working order.*
*Mitochondrial DNA Damage and Animal Longevity: Insights from Comparative Studies
Reinald Pamplona Department of Experimental Medicine, Faculty of Medicine, University of Lleida, IRB, Lleida, c/Montserrat Roig-2, 5008 Lleida, Spain
Received 8 September 2010; Revised 16 November 2010; Accepted 4 January 2011
REFERENCES 1. Pamplona R. Mitochondrial DNA Damage and Animal Longevity: Insights from Comparative Studies. Journal of Aging Research. Vol. 2011, Article ID 807108, 9 pages, 2011. doi:10.4061/2011/807108. 2. Valero T. Mitochondrial biogenesis: pharmacological approaches. Curr Pharm Des. 2014;20(35):5507-5509. 3. Lopes C, et al. Revisiting Mitochondrial Function and Metabolism in Pluripotent Stem Cells: Where Do We Stand in Neurological Diseases? Mol Neurobiol. 2017;54(3):1858-1873.
SOURCE Textbook: The Metabolic Approach to Cancer: Integrating Deep Nutrition, the Ketogenic Diet, and Nontoxic Bio-Individualized Therapies. Winters N, et al
WHAT ARE THE HEALTH THREATS?
OXIDATIVE STRESS AND YOUR HEALTH
An increase of oxidative stress occurs when the cellular presence of free radicals and ROS increase and/or the capacity of the defense system is insufficient. When free radicals and ROS accumulate in the cells they can damage cellular structures throughout the body, especially cell membranes, DNA (genetic material), and mitochondria (where cells generate energy). As this cellular damage accumulates, our cells can’t function properly, and we develop a degenerative disease or we experience common symptoms of aging, such as reduced energy levels, creaky joints, wrinkled skin, among other conditions.
DISEASES LINKED TO THE PROCESS OF OXIDATIVE STRESS
- Endothelial dysfunction
- Skin aging
- Actinic keratosis
- Cardiac fibrosis
- Myocardial infarction
- Chronic inflammation
- Autoimmune disorder
- Chronic fatique
- Macular degeneration
- Retinal degeneration
- Chronic kidney disease
- Renal graft
- Rheumatoid arthritis
REFERENCES 1.Kehrer JP, et al. Free radicals and related reactive species as mediators of tissue injury and disease: implications for Health. Crit Rev Toxicol. 2015;45(9):765-98. 2. Periyasamy P, et al. Age-related cataracts: Role of unfolded protein response, Ca2+ mobilization, epigenetic DNA modifications, and loss of Nrf2/Keap1 dependent cytoprotection. Prog Retin Eye Res. 2017;pii:S1350-9462(17)30057-5. 3. Mishra V, et al. Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets. Pharmacol Ther. 2017;pii:S0163-7258(17)30221-8. 4. Calabrese V, et al. Redox regulation of cellular stress response in neurodegenerative disorders. Ital J Biochem. 2006;55(3-4):263-282. 5. Yang X, et al. Oxidative Stress-Mediated Atherosclerosis: Mechanisms and Therapies. Front Physiol. 2017;23;8:600. 6. de Almeida AJP, et al. Aging: Molecular Pathways and Implications on the Cardiovascular System. Oxid Med Cell Longev. 2017;7941563.
SOURCE Textbook: The Metabolic Approach to Cancer: Integrating Deep Nutrition, the Ketogenic Diet, and Nontoxic Bio-Individualized Therapies. Winters N, et al
THE SMART SOLUTION
FIGHTING OXIDATIVE STRESS
Healthy food and taking antioxidant supplements may be helpful to some small degree, but they’re incapable of sufficiently combating oxidative stress. The protein Nrf2 has been recently identified as “the master regulator” of the antioxidant response in the cell. Activating the Nrf2 protein increases the production of antioxidants enzymes. These enzymes function as potent antioxidants capable of neutralizing more than one million free radicals. This makes them one million times more effective than dietary antioxidants, which can only scavenge free radicals on a “one-to-one” basis.
Healthy food and antioxidant supplements may be helpful to some small extent, but they’re incapable of sufficiently combating oxidative stress.
PROTECT YOUR CELLS WITH NRF2 ACTIVATION
The Nrf2 pathway has been referred to as the master regulator of antioxidant, detoxification and cell defense gene expression. For that reason extensive research has been carried out to explore the Nrf2 pathway for health and anti-aging interventions. The Nrf2 pathway has been especially studied in various brain degenerative disorders including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, as well as autism, to name a few.
As researchers from the University of Colorado publishing in the journal Clinical Pharmacology: Advances and Applications have described, activation of the Nrf2 pathway may find clinical application in a variety of other conditions including atherosclerosis, HIV/AIDS, inflammatory bowel disorders, rheumatoid arthritis, type I diabetes, and even cancer.
The authors concluded:
The Nrf2 cell signaling pathway has been demonstrated to contribute to the regulation of a wide variety of antioxidant, detoxification, and cell survival genes. Under normal conditions, Nrf2 activation plays a largely protective, beneficial role, which has led researchers to examine ways in which individuals might harness Nrf2 activation for health benefits, including exercise, diet, dietary supplements, and pharmaceuticals.
It is now recognized that a variety of natural products act directly upon the Nrf2 pathway activating this life-sustaining part of our DNA. These include turmeric, green tea extract, as well as coffee.
After years of research, Dr. McCord developed a science-based, nutrigenomic supplement that activates the Nrf2 protein and significantly decreases oxidative stress in the cell. Study results, which followed the launch of this Nrf2 Synergizer in 2006, have ignited the interest of the scientific community and excited many scientists into researching the Nrf2 pathway.
This unique formula is protected by eleven patents. The age-dependent increase in lipid peroxidation (a marker of oxidative stress) was completely eliminated in individuals who took the Nrf2 Synergizer for 30 days. Lipid peroxidation in an older subject was reduced to the level of a 20-year-old.
REFERENCES 1. Lewis KN, et al. Nrf2, a Guardian of Healthspan and Gatekeeper of Species Longevity. Integrative and Comparative Biology. 2010;50(5):829-843. 2. Gao B, et al. The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders. Clin Pharmacol. 2014;6:19-34. 3. Nagata N, et al. Glucoraphanin Ameliorates Obesity and Insulin Resistance Through Adipose Tissue Browning and Reduction of Metabolic Endotoxemia in Mice. Diabetes. 2017;66(5):1222-1236. 4. Xue M, et al. Activation of NF-E2-related factor-2 reverses biochemical dysfunction of endothelial cells induced by hyperglycemia linked to vascular disease. Thornalley Diabetes. 2008;57(10):2809-2817. 5. Johnson DA, et al. Nrf2–a therapeutic target for the treatment of neurodegenerative diseases. Free Radic Biol Med. 2015;88(B):253-267. 6. Denzer I, et al. Modulation of mitochondrial dysfunction in neurodegenerative diseases via activation of nuclear factor erythroid-2-related factor 2 by food-derived compounds. Pharmacol Res. 2016;103:80-94. 7. Johnson JA, et al. The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci. 2008;1147:61-9. 8. Liddell JR, et al. Are Astrocytes the Predominant Cell Type for Activation of Nrf2 in Aging and Neurodegeneration? Antioxidants (Basel). 2017;18:6(3). 9. Sandberg M, et al. NRF2-regulation in brain health and disease: Implication of cerebral inflammation. Neuropharmacology. 2014;79:298-306.
10. Hybertson BM, et al. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Mol Aspects Med. 2011;32(4-6):234-246. 11. Pall ML, et al. Nrf2, a master regulator of detoxification and also antioxidant, antiinflammatory and other cytoprotective mechanisms, is raised by health promoting factors. Acta Physiologica Sinica. 2015;67(1):1–18. 12. Poljsak B. Strategies for Reducing or Preventing the Generation of Oxidative Stress. Oxidative Medicine and Cellular Longevity. vol. 2011, Article ID 194586, 15 pages, 2011. doi:10.1155/2011/194586. 13. Egea J, et al. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS). Redox Biol. 2017;13:94–162.
SOURCE From the symposium ‘Metabolism, Life History and Aging’ presented at the annual meeting of the Society for Integrative and Comparative Biology, January 3–7, 2010, at Seattle, Washington.
NRF2 ACTIVATION IN SEVERAL DISEASES
Click on a link below for the search results in The US National Library of Medicine – National Institute of Health.
NRF2 VS ANTIOXIDANTS
WHAT DO ANTIOXIDANTS DO?
Our bodies produce free radicals (unstable molecules that cause oxidative stress) during normal metabolic functions and even more when we are exposed to stressors (i.e. air pollution, alcohol, cigarette smoke, or sunlight). When our bodies are overexposed to free radicals, we are at risk for premature aging and various diseases because free radicals destroy the cells and the tissues of our bodies.
The antioxidants, such as vitamin A, C and E, selenium, zinc, carotene, and flavonoids, are known to be present in our cells as part of the defense system to protect our bodies from the damaging effects of free radicals. This is the rationale of taking antioxidants. The use of multivitamins/minerals (MVMs) has grown rapidly over the past several decades, and dietary supplements are now used by more than half of the adult population in the United States.
WHAT KIND OF ANTIOXIDANTS DO WE HAVE?
On a daily basis, we use different types of antioxidants:
The ones we take (exogenous)
- Supplements as synthetic vitamins. Supplements as synthetic vitamins. How effective are they? Many clinical trials in which individuals received one or more synthetic antioxidants failed to obtain beneficial results or increased even the mortality. Results of clinical trials on exogenous antioxidants intake are thus conflicting and contradictory. There are evidently homeostatic mechanisms in cells that govern the amount of allowable antioxidant activity. Therefore, the intake of only one antioxidant could alter the complex system of endogenous antioxidative defense of cells, or alter the necrosis or apoptosis pathways.
Changing the level of one antioxidant causes a compensatory change in others, while the overall antioxidant capacity remains unaff ected. Dosing cells with exogenous antioxidants might decrease the rate of synthesis or the uptake of endogenous antioxidants, so that the total “cell antioxidant potential” remains unaltered. Antioxidant supplements thus do not appear in significantly decrease oxidative stress or/and increase life expectancy in humans.
- Food. Studies showed that individuals who consume more fruit and vegetables had a better cardiovascular health and decreased cancer incidence. This indicates that other substances in fruits and vegetables, or a complex mix of substances (e.g., inhibitors of P450 (grapefruit, garlic), inhibitors of cell proliferation (resveratrol, green tea polyphenols, and curcumin), antagonists of estrogen (flavonoids), inhibitors of metastases (flavonoids), and inhibitors of angiogenesis (genistein, epigallocatechin galate), may contribute to this effect.
The ones we make (endogenous)
- Antioxidant enzymes, produced in the body, are far more powerful than dietary antioxidants at stabilizing free radicals. Your body regulates the production of these enzymes, dependent on the balance between antioxidants and free radicals in your cells.
ANTIOXIDANT VS ANTIOXIDANT ENZYMES
Here’s how supplementary antioxidants (for example, Vitamin C) and antioxidant enzymes compare:
- One exogenous antioxidant molecule from an supplement removes one toxin.
- One endogenous antioxidant enzyme can be used over and over again to remove up to one million of toxins.
If you can increase your body’s production of an antioxidant enzyme like superoxide dismutase (SOD) by 2,000 mg per day, it can neutralize up to 5,270,000 moles of free radicals per day.
If you rid yourself of the free radicals that jumpstart the aging process in your body, you will need to determine how your body can produce more antioxidant enzymes.
HOW DO I STIMULATE MY BODY TO MAKE ITS OWN ANTIOXIDANTS ENZYMES?
The strongest defense system against free radicals is already present in your cells. The only thing you have to facilitate, is the production of antioxidant enzymes in your body. The basic concept behind this approach is ‘Hormesis’. The idea of hormesis is to provoke the intrinsic capability of a body rather than to supply exogenous natural or synthetic antioxidants to try to compensate for age-related decline of physiological activities in the overall maintenance mechanisms of life. Hormetic pathways, activated by phytochemicals, may involve kinases and transcription factors that induce the expression of genes that encode antioxidant enzymes. Specific examples of such pathways include the sirtuin-FOXO pathway, the NF-kappaB pathway, and the Nrf2/ARE pathway. For example, activation of the Nrf2/ARE pathway by sulforaphane and curcumin was observed. More than 60 other molecules were described that induce the Nrf2 network, most of them found in our daily diet.
The Nrf2 pathway
Whenever your cells are under stress, Nrf2, a protein, also known as the master regulator of the antioxidant defense system, tells your body to start making those protective molecules including antioxidant enzymes. It stimulates your body’s response to oxidative stress by cleaning up damaged cells, improving cell function, and activating a response that protects cells against future stress.
How can you activate your Nrf2 pathway and your body’s antioxidant enzyme production?
- Stop taking high-dose antioxidant supplements such as vitamins A, C, and E.
- Calorie restriction. Practice intermittent fasting once a month, consume only water for 24 hours.
- Daily moderate exercise.
- Sleep long enough and in complete darkness in order to produce necessary amounts of the endogenous powerful antioxidant melatonin and benefit from its particular role in the protection of nuclear and mitochondrial DNA.
- Eat the right variety of foods such as blueberries, onions, broccoli, cabbage, apples.
- Use a Nrf2 Synergizer with a unique blend of balanced phytonutrients. This combination of plant-based nutrients activates Nrf2 even further than when the nutrients are consumed separately.
REFERENCES 1. Poljsak B. Strategies for Reducing or Preventing the Generation of Oxidative Stress. Oxidative Medicine and Cellular Longevity. Vol. 2011, Article ID 194586, 15 pages, 2011. doi:10.1155/2011/194586. 2. Poljsak B, et al.Achieving the Balance between ROS and Antioxidants: When to Use the Synthetic Antioxidants. Oxidative Medicine and Cellular Longevity. 2013;2013:956792. 3. Benoist d’Azy C, et al.Oxidative and Anti-Oxidative Stress Markers in Chronic Glaucoma: A Systematic Review and Meta-Analysis. PLoS One. 2016;1;11(12):e0166915.