The key to good health is balance. If the chemicals and hormones within the body are within their respective normal limits, a person can be expected to remain relatively healthy. To obtain this optimum health it is important to realise the functioning of the body and how it copes with the constant bombardment of toxins. In this realisation we are able to feed it what it needs to promote the full functioning of each process. These processes fall within two categories, phase one and phase two.
The role of Phase 1 is dominated by the cytochrome P450 system. A cytochrome is a class of iron-containing proteins important for cell respiration, and it acts as a vehicle for the oxidation-reduction reactions of toxins. P450 is an enzyme associated with the conversion process of cholesterol to pregnenolone and, together is written CYP. Combined with a family, subfamily and a poly peptide it creates a human gene, written for example CYP2E1, which is an enzyme that breaks down alcohol in the liver.
Each phase one “family of microsomal proteins is responsible for a range of reactions, of which oxidation appears to be the most important.” However, oxidization is a bad situation as it causes a lot of free radical stress. This free radical stress leads to damage to the DNA of our bodies, and to our genes. Free radical stress must be minimized in the body. This is where phase two comes into play.
“The induction of phase two enzymes is considered an important mechanism of protection against chemical stress and carcinogenesis.” Phase one does all the damage and phase two cleans it up. Why do we have a phase one when it creates such a problem? Without phase one we would be unable to remove toxins from our bodies and they would continue to build up, as a result we would die. The human race would cease to be. Phase one takes a toxin breaks it, causing it to become more toxic. This broken toxin is now known as a free radical. Phase two then attaches an enzyme to the free radical, transforming it from lipid soluble to water soluble so it may be excreted from the body. The binding, or “glue” for enzyme to be attached to the free radical is obtained from green vegetables, fruit and nuts. This phase two process is the key to reducing cancer. By up-regulating phase two you enhance the body’s own ability to detoxify itself.
“Vitamin A is anti-carcinogenic! Retinoic acid, a modulator of cell proliferation and differentiation in lung epithelial cells, suppresses carcinogenesis in certain epithelial tissues.” The natural reaction to this statement is to say all we need to do is up regulate Vitamin A and we have found a cure for lung cancer. Yes and No! Beta Carotene being the problem. Beta Carotene is a pro vitamin, is an antioxidant and it is fat soluble. It is found in coloured vegetables such as carrots, pumpkin and any of the green vegetables. It is a precursor to vitamin A. In a publication by J. Nutr. 2003; Exposing ferrets to cigarette smoke and a pharmacological dose of B-carotene supplementation enhance in vitro retinoic acid catabolism in lungs via induction of cytochrome P450 enzymes, it is claimed that quote, “we found that cigarette smoke exposure, a pharmacological dose of B-carotene or their combined treatment for six months significantly lowers RA concentrations in lung tissue of ferrets and diminishes retinoid signalling”, end of quote. In effect it is being said that a pharmacological dose of B-carotene can in fact cause cancer. How? In the presence of cigarette smoke B-caratone, even though it is a precursor to vitamin A, will significantly reduce Vitamin A in lung tissue. As vitamin A is an antioxidant, the lungs are therefore under attack by free radicals, caused by the body’s own process of trying to break down and get rid of cigarette smoke out of the lungs, as there is insufficient phase two proteins to convert the free radicals into being water soluble, so as it can be expelled from the body. So what now? The same study showed that giving B-carotene at a low dose, actually had the opposite effect. It was found that an adequate supply of RA, enough to alleviate the problem, was found to be present in the lung tissue of the ferrets.
An extremely important organ that actively detoxifies the body is the liver. As the liver is so paramount in the detoxifying of the body any problems with it can have an incredible impact on the body as a whole. CYP2E1 is an enzyme that metabolises, several drugs and solvents within the liver. It has also been implicated in alcohol liver disease. CYP2E1 normally converts ethanol to a harmless acetic acid, otherwise known as vinegar, so it can be removed from the body, when both the ethanol and the CYP2E1 are within normal limits for this process. However, if there are not enough phase two proteins to attach to the ethanol once broken by CYP2E1 then it remains a dangerous hydroxyethyl radical. It has been found that obesity greatly up-regulates CYP2E1 production, thus its activity in the liver is also up-regulated in the morbidly obese, creating the problem of non-alcoholic induced fatty liver disease
Fatty Liver Disease is caused by CYP2E1 enzyme oxidative stress, which produces a substance that is toxic to the liver cells. However, it should also be said that by losing weight, the CYP2E1 down regulates and this may have beneficial effects within patients with non alcoholic fatty liver disease.
Dietary Glycine is claimed to be an effective therapy against liver damage, including that of chronic alcohol abuse and also a protector for the kidney against cyclosporine. There is also a possibility it may be useful clinically, for the treatment of sepsis, adult respiratory distress syndrome, arthritis, and other diseases with an inflammatory component, according to Wheeler MD, et. Al. Glycine: a new anti-inflammatory immunonutrient: Another such anti-inflammatory is Curcumin. Experimental studies have also shown it to prevent tumour cells and block carcinogen DNA.
Stress is a major factor in life today and it seems that no one person is able to avoid it. Not only is it emotionally disturbing, but stress has been directly linked to cardiovascular disease, by causing hypertrophy and hyperplasia of the smooth muscle cells in blood vessels throughout the body. The most detrimental effect is around the heart. Stress causes hypertension and atherosclerosis.
The enzymes connected to the functioning and good health of blood vessels is the CYP4A gene subfamily. The production of which is controlled by such things as “lipids, mineralocorticoids, sex hormones, fasting, starvation, insulin and diabetes.” According to Fleming, I. Inside CYP4A expressing vessels an increase in transmutable pressure would be expected to stimulate stretch-activated CA2+ channels, thereby enhancing smooth muscle 20-HETE formation and eliciting constriction” This is how CYP4A mediates blood pressure. Androgens, produced by the kidneys mediate the expression of this CYP4A enzyme and this is how the important role of blood pressure is controlled by the renal system.
Herb-Drug interaction is an important area. The potential for some herbs and foods to either up regulate or down regulate certain drugs due to their effects on certain enzymes. If they are prescribed when there is a conflict it can be detrimental to a clients wellbeing. Echinacea is one such herb that needs caution when prescribing. Others are grapefruit and St John’s Wort to name a few.
