Background: Manufacturers of cigarettes have admitted to adding ammonia since the 1960s to make them more addictive by boosting the absorption of nicotine significantly. This may make cigarette smoke more toxic to some including people that are more vulnerable such as young children with immature immune systems, the elderly or other individuals that have urinary impairments or genetic factors that alter excretory metabolism. Below are some examples of why adding ammonia to cigarettes may be indirectly responsible, at least in part, for the rise in cardiovascular and other diseases from smoking because of its toxic effects on genes and different tissues in the body.
In cells, chemical toxins effect metabolic pathways which may run parallel, are independant and/or interact, potentiate or possibly minimize the effects of each another. For this reason, it is difficult to predict the severity and the consequences of them on the health of an organism. Exposure to cigarette smoke is no different and has been shown to act differently in different people and on more than one molecular pathway at the same time. Through the years, hundreds of studies have demonstrated the health hazards associated with the toxic effects of smoking and one of these effects includes the dysregulation of metabolism including altering blood sugar homeostasis. Personally, I have suspected this to be the case for some time. Over the past several years, scientists have discovered smoking not only increases the risk for diabetes which includes higher glucose levels, higher insulin levels and increased blood pressure it may also contribute to episodes of hypoglycemia in diabetes. As one article state, "this may be due to an effect of smoking on insulin clearance, leading to hyperinsulinemia, increasing hypoglycemia, and worsening metabolic control. In addition, smoking has been shown to increase the secretion of hormones (i.e., growth hormone, vasopressin, and cortisol) that counteract insulin action, leading to an increased insulin requirement. Smokers have been found to require more insulin than nonsmokers to achieve the same level of glycemic control in some, but not all, studies." (Hirai)
In addition to ammonia making cigarettes more addictive, ammonia can act on the cortico-releasing factor (CRF) system which regulates behavior including feeding and increases serotonin and dopamine levels. As a consequence, it can influence mood and alter homeostasis leading the conditions like the weight loss and weight gain from smoking and cessation, respectively. Activation of this pathway, in fact, mediates psychological effects of nicotine withdrawal. (Grunberg) I recently mentioned that because ammonia activates the CRF pathway that regulates neuroendocrine, drug abuse responses and aversion one could relate MCS behaviors to a scewed form of addictive behavior. (Kreibich, Sahuque) More simply, its activation leads to changes in hormone production and alter behaviors, it is possible that abherrant signaling in this system may be responsible for some of the symptoms of MCS and similar to those from chemical withdrawal but modified into aversive response. It is also possible the addictive nature of smoking from ammonia or other volatiles on the CRF from smoke exposure could be a sensitizing factor, stimulate the immune system and also initiate a "loss of tolerance" which has been suggested as an explanation of multiple chemical sensitivity and sensitivities in autism. An interesting research study could be designed to determine wether a potential correlation of MCS sensitization and smoking could exist.
To support this idea further, researchers have demonstrated the addictive nature of smoking involves a cellular pathway called CREB that involves the relationship of reward to smoking behaviors and their association with environmental cues. Also, recent research findings show a strong association of CREB and CRF in stress-induced drug reward behavior. It is not beyond reason to suggest that alterations in signals that lead to physical and psychological symptoms of drug withdrawal may also influence physical and emotional aversive behaviors of MCS and argues against the notion of that symptoms of MCS are "psychosomatic". The high levels of cadmium may further disrupt the CREB pathway and normal cell functions. Both of these discoveries provide an important mechanism to explain activation of MCS by environmental cues and suggests that insulin resistance may play a part in some of its reactions. "Previously,it has been shown the CREB pathway keeps blood sugar in balance under certain metabolic conditions and excessive CREB activity in diabetes contributes to high blood sugar and insulin resistance. New findings show CREB encourages insulin resistance by lowering adiponectin and the insulin-sensitive glucose transporter 4 (GLUT4)." (US Health News) CREB is a mediator of inflammation and both of these findings demonstrate that overactive CREB may contribute to endothelial dysfunction and impair cognitive function by mediating inflammation and insulin resistance. (Ishiki) On the other hand, downregulation of the cGMP/NO/CREB by amyloid or hyperammonemia may contribute to neurodegenerative diseases and Alzheimer's. (Copper Mountain, CO, Puzzo) This has important implications not only for cigarette smoke but persistent organic pollutants considering they both may contribute to diabetes complications.Other environmental factors such as other exposures to heavy metals implicated in contributing to diabetes and altered methylation may also contribute to these conditions. (Pozharny)
Along those same lines, cigarette smoking also contributes to weight loss through activation of the aryl hydrocarbon and endoplasmic reticulum stress. In other blogs, I have suggested this process also is involved in MCS. A recent study agrees with findings that cigarette smoke and dioxin does lower adiponectin but also demonstrated that PPAR-gamma and c/EPB were also decreased. In another study, ornithine impairments in c/EPB knock-outs from hypoglycemia presented with significantly higher levels of ammonia. Further, it has been shown ornithine enzymes interact with C/EPB and is important for ammonia detoxification. Without it, you get impaired excretion of urea and gluconeogenesis. As one can see, metabolically cigarette smoke may cause severe alterations in metabolism. This may include alterations of ammonia which may potentially sensitize an individual towards development and contribute to multiple chemical sensitivity.
Citations and other documents available here.
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