Oxidative stress and lipid peroxidation are important factors that lead to environmental illness and other health problems. First, for the purpose of understanding, it is important to have an idea of the biological process of lipid peroxidation. According to Wipedia, lipid peroxidation refers to the “oxidative degration of polyunsaturated lipids where “free radicals” steal electrons from the lipids in cellular membranes. (1) Cells have membranes that surround them and their organelles that are prone to lipid peroxidation. Normal cellular membranes contain lipids, protein and polyunsaturated fatty acids (PUFAs) which allows for their fluidity. In a very complex process, initiation of reactive species generate multiple reactive molecules that attack membranes disrupting their structure and fluidity which consequently causes cellular dysfunction and tissue injury.
Lipid peroxidation begins when reactive species (ROS) such OH combines with hydrogen to make water and in this case a fatty acid radical.” (1) After production, these radicals, if allowed to go unchecked move about freely until they bump into a membrane where they can “steal” another electron. Reactive species are generated from normal cellular metabolism and in a homeostatic environment, reactive species generation is controlled and neutralized by antioxidants. However, in periods of environmental stress ROS are produced at much higher levels and when antioxidant stores are exhausted they are free to cause cellular damage. This unbalance in reactive species and available cellular antioxidants is referred to oxidative stress (2) and has been implicated in over 100 diseases and health conditions including those in environmental illness. In addition to oxygen there are other reactive species that include nitrogen, chlorine, bromine and sulfur and include radicals and non-radicals. The radicals superoxide, hydroxyl, hydrogen peroxide are three ROS species that promote lipid peroxidation.
Superoxides are highly reactive and commonly damage enzymes and cellular components and are generated by cellular processes including enzymatic reactions, the mitochondrial transport chain, the endoplasmic reticulum and endogenous bacteria. (3) In cells, the mitochondria are the biggest generator of superoxide and a prime target of peroxynitrate. (4) Unfortunately, mitochondria are extremely susceptible to their own oxidants that must be neutralized before they have opportunity to damage mitochondrial proteins, lipids, and DNA. It is believed the effects of oxidant damage over time leads to a number of health problems including neurodegenerative diseases and ageing due, in large part, to mitochondrial dysfunction and energy depletion. Reactive species can cause damage to the endoplasmic reticulum (ER) causing ER stress, an accumulation of unfolded proteins in the ER lumen and possibly cell death. (5)
Now that we understand a little bit more about reactive species, let’s focus on the role of oxidative stress, lipid peroxidation and their aldehyde by-products which cause “secondary damage” and are also factors in environmental illness because their formation reduces the effeciency of detoxification and can cause damage to proteins and DNA. In nature, there are exogenous aldehydes such as formalin and formaldehyde and endogenous aldehydes which are produced in the body. Most aldehydes are considered toxic but there specific toxicities differ depending on a person’s genetics, dose, and the chemical themselves. For instance, malondialdehyde and HNE are both aldehydes produced from lipid peroxidation of linoleic and arachadonic acids but HNE is more toxic than malondidaldehyde. In the body, the process of biotransformation of these aldehydes is achieved by the enzyme ADH. Therefore, the proper detoxification of aldehyde is dependant on adequate stores of ADH and in many individuals the stores of ADH are not always enough to meet the demand for the biotransformation of the aldehydes.
Aldehydes are formed both endogenously and exogenously. Endogenous aldehydes are derived in a number of ways including the breakdown of other toxicants, yeast, hormones, food we ingest and produced by intestinal bacteria and Candida. All of these aldehyde exposures, when combined, have the potential of exhausting antioxidant stores, activating inflammatory processes, increasing oxidative stress and slowing enzyme activities necessary for detoxification. The consequences of which are experienced, more acutely, in individuals who suffer from fibromyalgia, CFS, respiratory problems, neurological problems and other acute and chronic health conditions.
In a preceding blog, I mentioned the TRPA1 and TRPV1 nociceptors transmit pain and are implicated in neurogenic inflammation which is common in many of those who suffer from environmental illness. It has been shown, TRPA1 is activated by 4-HNE, a cytotoxic aldehyde produced when reactive oxygen species induce lipid peroxidation. (6 – 7) 4-HNE also has been shown to have negative health effects and high levels of the aldehyde have been found in patients with neurological diseases including Parkinson’s, Alzheimers and ALS. Lipid peroxidation is also associated with induction and exacerbation of autoimmune responses from chemical exposure as show in one study where exposure to trichloroethylene increased the formation of 4-HNE and malondialdehyde adducts in rat livers. (8)
Malondialdehyde is another product of lipid peroxidation and a biomarker for oxidative stress. In the early 90s, it was reported malondialdehyde may be a concern in the development of cancer of the thyroid and pancreatic cells and therefore is considerered a potential occupational carcinogen. (9) As one reviews the health studies on aldehydes, one finds numerous associations of increased malonaldehyde and other endogenous and immunogenic aldehydes in patients with conditions related to environmental illness including asthma, gastrointestinal problems associated with H pylori, neurodegenerative disease, chronic fatigue syndrome, heavy-metal poisoning and numerous others. For example, dust mites are small microscopic organisms that feed on dead skin and are considered a potential environmental hazard for those with asthma and allergies. It has been reported that individuals with dust mite infestations, presented with increased levels of malondialdehydes, higher levels of oxidative stress (10) and reduced levels of detoxification enzymes. Thereby increasing their risk for recurrence of their asthma and allergy-related symptoms. (11) Several studies including one on CFS patients found an increase in F2 Isoprontanes from lipid peroxidation of arachadonic acid (12), a fibromyalgia study found increases in malondialdehyde and concluded vitamins and omega 3 may be an important adjunct to other therapies (13) and lastly, higher levels of malondialdehyde were present in sheep with chronic heavy metal poisoning. (14) One can make an important assumption from this study; malonaldehyde can be used as a marker for lipid peroxidation from environmental exposures in other organisms not just humans. Exogenous exposures to aldehydes are usually from air pollution and pollutants and include acetylaldehydes which are also toxic aldehydes that can be found in cigarette and wood smoke.
With all this in mind, one must consider ways to limit exposures to exogenous and endogenous aldehydes. Admittedly, this is not always easy considering aldehydes are derived from sources all around us including food, air, pathogens and produced endogenously by bacteria and our own detoxification processes. However, there are several things a person can try to do to limit exposures to them:
- Reducing ones exposures to chemicals such as cleaning agents, detergents, etc. and reducing exposures to air pollution.
- Aldehydes are endogenously produced and therefore, limiting exposures that cause oxidative stress such as limiting alcohol consumption, take perscription drugs only when necessary, improving gut health and reducing sugar intake to reduce Candida overgrowth may be beneficial.
- Advocate for local and statewide bans on smoking and open leaf and wood burning to help reduce environmental pollution and associated aldehyde levels.
- Monitor indoor air quality and properly maintain, repair or replace home appliances that may be adding to poor indoor air quality such as unvented stoves, clean air ducts, etc. to reduce oxidative stress and other health effects from exogenous aldehydes and inflammation that activates other processes that generate endogenous aldehydes.
- Read labels on your food. If you do not eat organic, notice how many chemicals on the labels are listed as nitrogen, sulfur, phosphates, etc. and may be chemical irritants to the gastrointestinal tract. If you read a food label and can not pronounce it or spell it, then you might want to think again about eating it!
- To reduce oxidative stress from normal digestion, eat plenty of vegetables with your meal!!
- Again, limit your sugars and lower the “bad” fat content of your food! They can cause inflammation.
HEIRS Nutrition News Net on HEIRS Feeds
- Purple sweet potato leaves reduce lipid peroxidation and DNA damage in humans.
- A recent study shows positive evidence that ginseng health benefits are a result of the herbs ability to weaken oxidative stress and mitochondrial disfunction.
Kimberly Kramer
Health Educator and Researcher
Health Education Information and Resource Services
www.heirs-online.com
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(1) Lipid Peroxidation. Wipedia: The Online Encyclopedia. Retrieved on September 28, 2008.
(2) Reactive oxygen species. Wipedia. The Online Encyclopedia. Retrieved on September 28, 2008.
(3) Halliwell, B. and Gutteridge, J. M. C. (2007). Free Radicals in Biology and Medicine. Oxford University Press, Great Clarendon St. Oxford OX2 6DP, 4th edition. http://www.citeulike.org/user/HEIRS/article/3347738
(4) Pall, Martin, PhD., (2007) Explaining Unexplained Illnesses. Haworthe Press. 446 pgs.
(5) Kaufman, R. J. (2002). Orchestrating the unfolded protein response in health and disease. J. Clin. Invest., 110(10):1389-1398. http://www.citeulike.org/user/HEIRS/article/3347754
(6) Trevisani, M., Siemens, J., Materazzi, S., Bautista, D. M., Nassini, R., Campi, B., Imamachi, N., Andrè, E., Patacchini, R., Cottrell, G. S., Gatti, R., Basbaum, A. I., Bunnett, N. W., Julius, D., and Geppetti, P. (2007). 4-hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor trpa1. Proceedings of the National Academy of Sciences of the United States of America, 104(33):13519-13524. http://www.citeulike.org/user/HEIRS/article/3346232
(7) Chao (2008). Trpa1: The central molecule for chemical sensing in pain pathway? The Journal of Neuroscience, 28(5):1019-1021. http://www.citeulike.org/user/HEIRS/author/Chao
(8) Wang, G., Ansari, G. A. S., and Khan, F. M. (2007). Involvement of lipid peroxidation-derived aldehyde-protein adducts in autoimmunity mediated by trichloroethene. J Toxicol Environ Health, 70(23):1977-1985. http://www.citeulike.org/user/HEIRS/article/3346874
Filed under: environmental illness | Tagged: 4-HNE, acetylaldehyde, Air Quality, aldehydes, allergies, antioxidants, asthma, biotransformation, Candida, chemical exposure, Chronic Fatigue Syndrome, cigarette smoke, dust mite, environmental illness, fibromyalgia, formaldehyde, free radicals, Heavy Metal Poisoning, lead poisoning, lipid peroxidation, malondialdehyde, mitochondria, multiple chemical sensitivity, neural, oxidative stress, Parkinson's Disease, PTSD, reactive oxygen species, ROS, superoxide, TRPA1, TRPV1, wood smoke
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