Abstract
Stress reduction is a major theme of the recommendations in this book. Oxidative stress is “stress” at the cellular level. Arguably, the most critical damage caused by oxidative stress is to mitochondria function. There is a direct causal relationship between oxidative stress, mitochondrial dysfunction, and many clinical syndromes, especially those that may be relieved but are difficult to cure, including parasympathetic and sympathetic dysfunctions. Reducing mitochondrial dysfunction is the beginning to the cure of many of these syndromes and a critical step on the path to wellness. A little oxidative stress is healthy. Too much oxidative stress accelerates diseases and ultimately the aging process, destroying mitochondria, and thereby cells, and thereby membranes, and thereby tissues, and ultimately organs and organ systems. While mitochondria, when they themselves are dysfunctional, contribute to oxidative stress, the reactive species they produce normally are helpful to the body, including the immune system, contributing to the passive defense, literally “burning out” foreign agents. Reducing oxidative stress also helps to maintain proper nitric oxide function which feeds back and helps to further reduce stress, preventing the dark side of nitric oxide. The main object of this chapter is to demonstrate means of reducing oxidative stress and how reducing oxidative stress helps to relieve diseases and establish and maintain wellness.
A proper antioxidant reservoir and maintaining a proper antioxidant-oxidant balance are the keys to minimizing oxidative stress effects. A proper reservoir is built on supplements including alpha-lipoic acid and CoQ10; B vitamins, including folic acid (vitamin B9); tryptophan; and nitric oxide.
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Notes
- 1.
The day you are born, your body creates pre-cancer cells. Cancer is simply a mass of your own cells that did not divide properly so that they begin to grow outside the checks and balances of your own body. It is a purpose of your immune system, beginning the day you are born, to find all of these cells and destroy them. As immune systems age and slow, some cells may be missed, and a tumor is permitted to start because the tumor cells are not “tagged” for destruction and therefore are assumed to be a normal part of the body.
- 2.
The singlet oxygen which is not a free radical per se, yet it is still unstable. O2 is preferred, not O.
- 3.
Open Access, Springer Nature.
- 4.
The sperm and ovaries do not have a full complement of chromosomes, only half. If the immune system had access to them, as it does most of the rest of the body, they would be considered foreign and would constantly be attacked.
- 5.
Arsenic is found in trace amounts in apple seeds, among others, and, perhaps due to its affinity to ALA, helps to kill pre-cancer cells, another example where “bad things” are not all bad. However, any more than trace amounts and arsenic becomes bad. This gives more meaning to “an apple a day keeps the doctor away.”
- 6.
This is considered a non-modifiable risk factor.
- 7.
Dismutation is the simultaneous oxidation and reduction chemical reaction.
- 8.
This sympathetic over-activation, as referenced three times in this section, is a relative term. It is not an absolute term. In other words, it is a sympathetic level that is excessive when compared to the corresponding parasympathetic level. There should be a balance. In the resting state, sympathetic to parasympathetic balance (aka sympathovagal balance or SB, as measured by P&S Monitoring) should be near 1.0. Sympathetic excess is defined as resting SB > 3.0, regardless of the absolute levels of sympathetic or parasympathetic activity.
- 9.
Intentional and temporary cessation of cardiac activity, primarily for cardiac surgery
- 10.
Troponin I is involved in muscle contraction and is a marker of heart attack in the bloodstream.
- 11.
UQ10-H2 is the molecular name for CoQ10. UQ is the abbreviation for ubiquinone, the oxidized form, or ubiquinol, the reduced form. The latter is the useable form. The former is immediately transformed to the latter in the body. Either way, it is essential in the function and health of mitochondrial electron transport and the production of ATP.
- 12.
Myoglobins provide muscle cells reserve stores of oxygen for periods of intense activity. Ferri and Met forms of myoglobin provide more efficient means of storing oxygen.
- 13.
Melatonin, when taken as a supplement, cannot cross the blood-brain barrier. When the brain senses increased levels of melatonin outside the brain due to supplementation, it assumes more melatonin than needed is released. In response, the brain increases levels of available serotonin inside the brain to maintain the apparent proper balance. This then simulates the serotonin-melatonin balance of evening and helps to mediate the process of falling asleep.
- 14.
Steno-2 trial involved patients with T2DM and microalbuminuria. Intensive pharmacological intervention targeting hypertension, hyperlipidemia, and microalbuminuria, combined with behavioral treatment (exercise, diet, and smoking cessation), reduced the risk of autonomic neuropathy over the course of a 7.8-year follow-up. The risk for developing CAN was significantly lower on the intervention arm (49% in the intensive group vs. 65% in the conventional group; HR = 0.37; 95% CI, 0.18–0.79; p = 0.002). After a mean of 5.5 years following the end of the study, the same protective effect against the development of autonomic neuropathy persisted (RR = 0.53; 95% CI, 0.34–0.81; p = 0.004). There was also reduction in the risk for developing CVD (RR = 0.43; 95% CI, 0.19–0.94; p = 0.04) and overall mortality (RR = 0.54; 95% CI, 0.32–0.89; p = 0.02) in this study.
- 15.
With nerve conduction velocity (NCV) studies, a very small electrical current is passed through the nerve bundle to determine conduction time. Of course, electricity takes the path of least resistance, meaning that it will preferentially flow through the large nerve fibers, not the small fibers. Therefore, NCV is a measure of large fibers, which are the sensory and motor fibers, not the P&S (or autonomic) nerve fibers. This is why vibration and pin prick tests are well correlated. In general, if the patient can feel the stimulus, it is not an autonomic test.
- 16.
Zenarestat (FK-366; FR-74366) is a powerful aldose reductase inhibitor which inhibits the metabolism of glucose by the polyol pathway, to slow or reduce progression of polyneuropathy. It was investigated as a treatment of diabetic neuropathy and cataract, but its development was terminated.
- 17.
Fidarestat (SNK-860) is a potent aldose reductase inhibitor under investigation for treatment of diabetic neuropathy. Fidarestat normalized the elevated sorbitol content of erythrocytes under fasting as well as postprandial conditions and possibly useful for both preventing and treating diabetic neuropathy.
- 18.
Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. Long-term treatment is well tolerated and can effectively delay the progression of diabetic neuropathy and ameliorate the associated symptoms of the disease, particularly in people with good glycemic control and limited microangiopathy.
- 19.
Dihydrolipoic acid is an organic compound, that is, the reduced form of lipoic acid. Only its R-enantiomer is biochemically significant.
- 20.
Sudomotor testing measures the activity level in small peripheral nerves and is useful in detecting peripheral autonomic neuropathy; however, it does not differentiate between parasympathetic and sympathetic dysfunction.
- 21.
In addition to sympathetic-adrenergic nerves, the heart is innervated by parasympathetic-cholinergic nerves derived from the vagus nerves. Acetylcholine (ACh) released by these fibers binds to muscarinic receptors in the cardiac muscle, especially at the SA and AV nodes that have a large amount of vagal innervation. ACh released by vagus nerve fibers binds to M2 muscarinic receptors, a subclass of cholinergic receptors. This produces negative chronotropy and dromotropy in the heart, as well as negative inotropy and lusitropy in the atria (the negative inotropic and lusitropic effects of vagal stimulation are relatively weak in the ventricles).
- 22.
Republished with permission from Oxford University Press.
- 23.
Adapted from Shutterstock Royalty-free stock vector images ID: 1030576897. Different stages of human liver illustration, by BlueRingMedia.
- 24.
- 25.
Selective inhibition of nNOS over related isoforms (eNOS and iNOS) is therapeutically desirable.
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DePace, N.L., Colombo, J. (2019). Oxidative Stress Reduction (Prong-3). In: Clinical Autonomic and Mitochondrial Disorders. Springer, Cham. https://doi.org/10.1007/978-3-030-17016-5_5
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