Rusting on the Inside from Oxidative Stress - February 2017

By Dr. Greg Fors - Board Certified Neurologist

Do you or anyone you know suffer with chronic pain and fatigue? Part of the problem may be that you’re rusting on the inside from oxidative stress. Oxidative stress occurs when the level of free radical damage to cellular structures is inadequately kept in check by endogenous and exogenous antioxidants. Free radicals are among the most damaging agents to your health. In simple terms, a free radical is a hungry and unstable molecule containing one or more unpaired electrons in its outer orbit. Free radicals seek to steal electrons from other functional molecules, often leaving damage to the cell behind. In particular, free radicals love to attack polyunsaturated membrane lipids, DNA and amino acids. When free radicals steal electrons, a chain reaction occurs that results in cellular chaos. Once begun, this process can become a feed-forward cycle, and difficult to control. It’s hard to imagine such devastation coming from such tiny molecules that only live for a few thousandths of a second.

Even in healthy individuals, chromosomes are susceptible to tens of thousands of free radical hits daily, which cells and their structures must ward off. The trouble begins when free radicals disrupt the structure and function of cellular membranes, and interfere with enzymes that serve to regulate reactions within the body. Research has established free radical damage as one of the primary mechanisms by which degenerative disease and aging accelerates. The destruction from free radicals grows in severity when cellular DNA is disrupted, and regulatory genes are unable to repair the damage. These disruptions in the genetic code are what ultimately lead to devastating consequences like cancer. Recent studies have proven that environmental and nutritional factors, including pollutants, radiation, pesticides, various medications, and deep fried foods, as well as physical stress, can produce massive amounts of free radicals that contribute to tissue injury, disease, and aging.

Chronic systemic inflammation is almost always at the root of dysfunction and disease, and free radicals are responsible for igniting this inflammatory cascade. Therefore, when addressing chronic myofascial pain, which is always connected to systemic inflammation, the underlying oxidative stress must first be dealt with. Specifically, free radicals exert their actions by activating Nuclear Factor kB (NF-kB), a signaling pathway that induces the synthesis of proinflammatory cytokines. Eventually, these free radicals at the site of inflammation begin to damage various cellular components, which increases free radical generation and additional tissue inflammation. This feed-forward cycle eventually causes a loss of function and cell death, and the tangible outcome is observed as pain, aching, fatigue and brain fog. If corrective actions are not taken to disrupt this vicious inflammatory cycle, it can be very difficult to achieve a lasting recovery. One of the best ways to disrupt this vicious feed-forward cycle is through adequate antioxidant therapy.

In clinical practice, I believe the antioxidants vitamin E, primarily that of gamma tocopherol, and pH balanced Ester-C are essential for patients with oxidative stress. Experimental data suggests that vitamin E is the primary lipid-soluble small molecule antioxidant, and vitamin C is the terminal water-soluble small molecule antioxidant. Vitamin E is located within the cellular lipid membrane, while vitamin C is located in cellular aqueous phases. Additionally, vitamin C is able to recycle vitamin E; specifically, vitamin C repairs the tocopheroxyl (chromanoxyl) radical of vitamin E, thereby permitting vitamin E to function again as a free radical chain-breaking antioxidant in the lipid membrane. In this way, vitamin E and C cooperate to protect lipids and lipid structures against peroxidation and free radical damage.

As you may know, primates, including humans, are unable to produce their own vitamin C. Yet, the majority of the animal kingdom maintains the ability to self-synthesize this vital antioxidant in quantities dependent upon conditions of stress. Under heightened conditions of stress or infection in animals, self-synthesis of vitamin C in animals can quadruple. For most animals, under healthy conditions, the daily amount of self-produced vitamin C, adjusted for comparison to a 70kg man, is somewhere between 3,000 mg and 15,000 mg, with an average of 5,400 mg. Some primates appear to require a human equivalent of up to 2,800 mg a day to survive the long-term stresses of captivity.

When it comes to vitamin E, the issue is a bit more complicated. Most clinicians provide supplements high in alpha-tocopherol. Supplemental vitamin E alpha tocopherol with “mixed tocopherols” generally contains only alpha-tocopherol with a token quantity of the other vitamin E molecules. Recent studies now show that unbalanced alpha-tocopherol supplementation is actually harmful, and may raise mortality rates.1 Unbalanced alpha-tocopherol supplementation can deplete the body and brain of the other members of the vitamin E family, negating many of their benefits. For example, after just one month of supplementing with 400 IU of alpha-tocopherol, gamma-tocopherol levels in individuals were reduced by a whopping two-thirds. Furthermore, once unbalanced alpha-tocopherol supplementation is stopped, it can take as much as two years for the ratio of alpha- and gamma-tocopherol to return to normal!2 By contrast, gamma-tocopherol supplementation can in fact raise alpha-tocopherol levels.

It is gamma-tocopherol that is the most effective in detoxifying the extremely damaging “reactive nitrogen species.” In fact, alpha-tocopherol alone is ineffective at removing the key reactive nitrogen species called peroxynitrite. Therefore, alpha-tocopherol with “mixed tocopherols” supplementation can result in increased oxidative stress that promotes a functional decrease in antioxidant capacity, leading to a functional increase in inflammation, and hence, the potential increase in mortality rates.3 Supplementation with gamma-tocopherol, but not alpha-tocopherol, significantly lowers C-reactive protein concentrations and can triple PPARγ mRNA levels, which act as anti-inflammatory mediators.4

In summary, consider the potential benefits of antioxidant therapy from quality vitamin C and E (gamma-tocopherol) supplements, especially during times of increased stress, or inflammatory states. Furthermore, it is important to understand that there is no substitute for a healthy diet and lifestyle. Certain nutritional interventions, including forms of antioxidant therapy, may prove very beneficial, however, they should not be used as a substitute or buffer for unhealthy lifestyle choices. Only with proper nutrition, exercise, stress management, avoidance of toxic substances, and nutraceutical support when necessary, can you prevent yourself from rusting on the inside from oxidative stress.

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Dr. Greg Fors, D.C. is the Chief Science Consultant for Biospec Nutritionals, a Board-certified Neurologist (IBCN), certified in Applied Herbal Sciences (NWHSU) and acupuncture. Trained through the Autism Research Institute he is a registered 'Defeat Autism Now!' Doctor. As the clinic director of the Pain and Brain Healing Center in Blaine Minnesota he specializes in a natural biomedical approach to fibromyalgia, fatigue, depression, autism and ADHD. He is a sought after international lecturer for various post graduate departments and state associations. Dr. Fors is the author of the highly acclaimed book, "Why We Hurt" available through booksellers everywhere.


  1. Ann Intern Med. 2005 Jan 4;142(1):37-46. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality.Miller ER 3rd, Pastor-Barriuso R.
  2. Baker H, Handelman GJ, Short S, Machlin LJ, Bhagavan HN, Dratz EA, Frank O. “Comparison of plasma alpha and gamma tocopherol levels following chronic oral administration of either all-rac-alpha-tocopheryl acetate or RRR-alpha-tocopheryl acetate in normal adult male subjects.” Am J Clin Nutr. 1986 Mar; 43(3): 382-7.
  3. Handelman GJ, Machlin LJ, Fitch K, Weiter JJ, Dratz EA. Oral alpha-tocopherol supplements decrease plasma gamma-tocopherol levels in humans. J Nutr. 1985;115(6):807-813.
  4. Reiter E, Jiang Q, Christen S. Anti-inflammatory properties of a- and γ-tocopherol. Mol Aspects Med . 28 (2007) 668-691.