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Oxidative Stress in Disease Progression

2/4/2020

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Over 125 clinical diseases have been linked to oxidative stress as a major cause or contributing factor to disease progression. Oxidative stress refers to chemical stress at a cellular level. When not correctly managed naturally by antioxidants in the body, these chemicals wreak havoc causing inflammation, physical stress, and in the end disease.
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Biology 101 - Cell Structure

To fully understand oxidative stress, you must first understand cell structure. Cells are the building blocks of, well, you. You are made of trillions of cells, all differentiated to their specific system and job. Each cell is like its own little organism with an external layer, cytoplasm liquid inside, and organelles that do different jobs.

The outer layer is call the phospholipid bilayer, and it makes up the "skin" of the cell. The job of the bilayer is to control what comes in and out of the cells, and add protection.

Within the cells, cytoplasm makes up the liquid, jelly-like, portion.

The nucleus is the control center, or the "brain" of the cell. The nucleus houses your DNA and depending on what type of cell we are talking about, is responsible for coding different enzymes and functions.

They cytoplasm organelles are small "organs" that are suspended in the cytoplasm. Some regulate the production of proteins coded by the nucleus. Some recycle dead components, bacteria, and viruses. Some package chemicals to be transported out of the cell and into the body. Some (the mitochondria) convert the calories you consume into energy and so much more. 

Mitochondria and Krebs

Mitochondria are the power source of the cells, and your body. This is where your body turns the calories you eat, the water you drink and the oxygen you breathe into energy that fuels life...mitochondria are very important. 

The chemical cycle that converts these macronutrients into energy is called the Krebs Cycle, or Citric Acid Cycle. I absolutely love this cycle...in fact it was one of the first science topics I taught my kids (they asked how food became energy, it was their fault).

The Krebs cycle consists of 8 steps. Each step requires water, oxygen and vitamins (specifically B vitamins, but also vitamin C, Coenzyme Q10, & Magnesium). Each step also produces a natural byproduct...a chemical pollutant. This is an engine turning fuel into energy (ATP) and just like the engine of your vehicle it produces heat, energy & pollutants that must be neutralized. 

Understanding Oxidative Stress

In comes antioxidants; the antioxidants your body makes through other biological functions (such as folate Methylation and B6 enzymes) and the antioxidants you consume through your diet. 

This production of pollution is natural oxidation...think of it as the exhaust from our engine. If you sit in an enclosed garage and have no way of neutralizing or removing the exhaust you get very sick and can die from the toxic buildup. The same thing happens in the body. If you have a continual buildup of these oxidants and do not remove them the cells get sick and can die...and if  your cells get sick and die, you have disease and in the end death.

The mitochondria also house some DNA, which has been known to mutate under oxidation. When the Mitochondria replicates, these mutations also replicate. So when the damage occurs in one mitochondria it is passed down to future mitochondria and you get generations of organelles that carry diseased DNA. 

Another thing we see is that when a cell cannot convert calories into energy (we see an insufficiency in the Krebs cycle with oxidation), the cell actually goes into a process called apoptosis or cell death. A natural way of clearing out dysfunctional cells. When the body is riddled with oxidation, though, we see lots of cell death. 

Some level of oxidative stress is a normal part of aging. As we get older, our natural production of antioxidant enzymes goes down and future generations of mitochondria become weaker...thus, we get older. This is a natural progression with age.

When we see oxidative stress and aging cells before their time, this is disease. 

Oxidative Stress Causes

So, what would cause an imbalance in the ratio of oxidative compounds and antioxidants...well, a couple of things:
  • Environmental Toxins - I put this first because it is very common to see a buildup of other ROS (Reactive Oxygen Species) from environmental pollution, pesticide use, heavy metal exposure, viruses, bacterial infections etc... This puts an additional stress on the cells. The natural production of antioxidants is unable to keep up with the growing amount of toxicity and the ratio becomes imbalanced and disease occurs. This can also include smoking, one of the reason that smokers tend to age quicker, and chronic use of certain medications.
  • Nutritional Deficiencies - This is my second because it is more common than you thing. Each step in the Krebs cycle requires vitamins and minerals to function. In addition, the formation of naturally occurring antioxidants often requires multiple vitamins and minerals to be formed or to function. A deficiency in any individual or group of nutrients could cause a dysfunction in the system and increase oxidative stress
  • Genetics - Certain genetic mutations are known to increase the risk of oxidative stress
  • Poor Diet - You would think this would fall into the category of nutritional deficiencies, but there are other dietary aspects that can increase oxidative stress. Consuming excess sugars, processed fats, processed foods full of chemicals, and overall junk food can increase oxidative stress by adding in highly processed chemicals that increase oxidation. Pair that with nutritional deficiencies and diets low in antioxidants and you have a recipe for cellular oxidation...aka the Standard American Diet.

Oxidative Stress & Disease

Long term oxidative stress increases cellular inflammation, weakens metabolism, damages DNA, and causes cell death. Certain organ systems are more likely to be affected by oxidative stress.
  • Cardiovascular - The heart and blood vessels are sensitive to damage, and changes in how the system functions can be life threatening. High blood pressure, atherosclerosis, migraines and stroke have all been linked to oxidative stress
  • Neurological - The brain is highly sensitive to oxidative stress. Your neurons on your biggest user of glucose and the mitochondria are working overtime to provide enough energy for your cells to create rapid fast signalling. Dementia, alzheimer's, parkinsons, depression, anxiety, chronic fatigue, and essential tremors have all been linked to oxidative stress
  • Immunology - The link between the immune system and oxidative stress has been well established through the development of cancer. It can also be seen in the progression of autoimmune disease
  • Metabolic - It would seem to be a no brainer that a oxidative stress that affects the area of cells where metabolism (the conversion of food into energy) occurs would have an impact on metabolism. Oxidation of cells can cause you to become excessively hungry with low energy and weight gain. It can also be a cause of type 2 diabetes, insulin resistance, and other conditions associated with poor metabolism.
  • Hormones - The organs that produce hormones; ovaries, testes, adrenal glands, are highly affected by oxidative stress. Oxidatives "stress" raises cortisol, and have the same reactions in the body as elevated cortisol due to perceived stress. The ovaries and testes produce the hormones necessary for reproduction, and oxidative stress is highly associated with infertility in both men and women.
  • Pregnancy - Many of the growing complications in pregnancy have a link to oxidative stress. The placenta, in particular, is very vulnerable to oxidation. When the placenta shows signs of oxidation it cannot function properly. Preeclampsia, gestational diabetes, intrauterine growth restriction, childbirth complications, and postpartum depression have all been linked to oxidative stress.

Prevention & Treatment

You  have probably already heard me say this before, "prevention is easier than treatment." The lifestyle and diet you choose influences your propensity for oxidative stress disease.
  • Choose nutrient dense foods and eat a balance diet
  • Avoid processed fats
  • Avoid processed sugars
  • Exercise regularly
  • Quit smoking or using chewing tobacco
  • Don't vape
  • Don't over consume alcohol - Red wine is actually a good source of antioxidants
  • Reduce stress - perceived, endogenous & exogenous
  • Reduce exposure to pollutants and environmental chemicals - cleaning agents, pollution, pesticides, etc...

If you have a disease that is linked to oxidative stress, all of the above are also important in treatment, but you may need extra support. 
  • Supplemental antioxidants - depending on your disease pattern and progression, specific antioxidants can be used to reduce cellular oxidation. Not every antioxidant is the right antioxidant.
  • Nutritional supplements - if you do have nutritional deficiencies, correcting these with diet alone may not work. Additional supplements are usually needed
  • Time - You didn't get here overnight, and recovery often takes time.

My Sources

  1. Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hypertens. 2000;18(6):655-673. doi:10.1097/00004872-200018060-00002
  2. Cervantes Gracia K, Llanas-Cornejo D, Husi H. CVD and Oxidative Stress. J Clin Med. 2017;6(2):22. Published 2017 Feb 20. doi:10.3390/jcm6020022
  3. Carvalho AN, Firuzi O, Gama MJ, Horssen JV, Saso L. Oxidative Stress and Antioxidants in Neurological Diseases: Is There Still Hope?. Curr Drug Targets. 2017;18(6):705-718. doi:10.2174/1389450117666160401120514
  4. Chen Y, Zhou Z, Min W. Mitochondria, Oxidative Stress and Innate Immunity. Front Physiol. 2018;9:1487. Published 2018 Oct 18. doi:10.3389/fphys.2018.01487
  5. Saha SK, Lee SB, Won J, et al. Correlation between Oxidative Stress, Nutrition, and Cancer Initiation. Int J Mol Sci. 2017;18(7):1544. Published 2017 Jul 17. doi:10.3390/ijms18071544
  6. Ruder EH, Hartman TJ, Goldman MB. Impact of oxidative stress on female fertility. Curr Opin Obstet Gynecol. 2009;21(3):219-222. doi:10.1097/gco.0b013e32832924ba
  7. Bisht, S., Faiq, M., Tolahunase, M. et al. Oxidative stress and male infertility. Nat Rev Urol 14, 470–485 (2017). https://doi.org/10.1038/nrurol.2017.69
  8. Lucilla Poston, Natalia Igosheva, Hiten D Mistry, Paul T Seed, Andrew H Shennan, Sarosh Rana, S Ananth Karumanchi, Lucy C Chappell, Role of oxidative stress and antioxidant supplementation in pregnancy disorders, The American Journal of Clinical Nutrition, Volume 94, Issue suppl_6, December 2011, Pages 1980S–1985S, https://doi.org/10.3945/ajcn.110.001156
  9. Mistry HD, Williams PJ. The importance of antioxidant micronutrients in pregnancy. Oxid Med Cell Longev. 2011;2011:841749. doi:10.1155/2011/841749
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