An excellent article in regards to grapefruit and CYPs 450. Many are unable to eat grapefruits following ADRs from Lariam, Fqs and other meds. Watch out if you are on meds. It is important to avoid grapefruit to avoid potentiating and toxicity. Read up on tangerines, mandarines, clementines, oranges.

Mechanism of Grapefruit Juice Interactions

Basic Mechanism of Action

Drugs that interact with grapefruit and/or grapefruit juice (GJ) undergo cytochrome p450 oxidative metabolism in the intestinal wall or liver. GJ contains various furanocoumarins which have been demonstrated to affect the cytochrome p450(CYP) system (especially at isoenzyme CYP3A4) by binding to the isoenzyme as a substrate and impairing first-pass metabolism, by direct inactivation or inhibition of the enzyme (mechanism-based inhibitors). The net effect on the CYP enzymes from this inhibition seems to be a selective down-regulation of CYP3A4 in the small intestine.26 For certain drugs which are known to be CYP 3A4 metabolized, less drug is metabolized prior to absorption, and greater amounts of these drugs reach the systemic circulation, leading to higher blood levels, and potentially to increases in therapeutic and/or toxic effects.

Naringin

Naringin is the main bioflavonoid in GJ. Naringin is not a potent CYP inhibitor, but is partially metabolized by enteral bacteria to naringenin, which is a potent inhibitor of p450 enzymes, and early research into GJ interactions proposed that naringin was the component of GJ responsible for the interactions,4-6 although it was thought possible that another unidentified component in grapefruit may also have been responsible, since giving naringin alone does not seem to cause the same degree of inhibition as GJ.4-5,21 Recent evidence clearly indicate that furanocoumarins, especially dihydroxybergamottin are the chemicals responsible for GJ interactions.

Furanocoumarins/Dihydroxybergamottin

Researchers have isolated a group of compounds from GJ called furanocoumarins, which appear to be specific CYP3A4 inhibitors.27-29 A study on extracts of GJ interacting with rat and human p450 found that naringin accounted for only 10% of the inhibition of CYP activity seen with GJ.28 In vitro results show that a compound known as 6',7'-dihydroxybergamottin may be the chemical which accounts for the difference in effects on CYP3A substrates caused by GJ versus naringenin.27 A separate study with in vitro data determined that several compounds found in GJ inhibit CYP3A4 enzymes. Specifically, these were nootkanone (a sesquiterpene), and 4 derivatives of coumarin, geranyloxycoumarin, bergamottin, and 2 chemical with very long technical names, denoted as GF-I-1 and 4.29 Additional CYP3A inhibitory chemicals GF-I-5, GF-I-6 and bergapten have also been identified.132 The concentrations of nootkanone and bergamottin required to inhibit CYP3A4 enzymes however, was found to be higher than the naturally occurring concentrations found in GJ.

Results of confirmatory in vivo testing of CYP3A4 inhibition with externally administered GF-I-1, GF-I-4, GF-I-5 and GF-I-6 have not been published at present. It should also be noted that wide inter-individual variability in response to these interactions have been documented in studies.2,11

Start of New Article A recent study determined that the chemical moiety 5-geranyloxyfurocoumarine is essential for CYP3A4 inhibitory activity. This moiety is found in dihydroxybergamottin, as well as GF-I-1 and GF-I-4.127 A total of 6 furanocoumarin derivatives are suggested to be clinically active constituents of GJ.129

Commercial manufacturing of GJ is a multi-step process that includes washing of unpeeled fruit prior to squeezing whole fruits to juice. After squeezing, juice is heated for pasteurization, and volatile components may evaporate. Grapefruit oil, an important constituent of grapefruit peel, is sometimes added to the concentrate as a flavor enhancer.

A study found that epoxybergamottin, a furanocoumarin extracted from grapefruit peel is also an inhibitor of CYP 3A4. This compound has previously been found in only minor quantities in GJ, compared to 6'7'-dihydroxybergamottin. The authors note that it is possible that this compound could be distributed into the juice, during the commercial juice manufacturing process. Epoxybergamottin is not chemically stable in acidic medium, and may become hydrolyzed to 6'7'-dihydroxybergamottin.134

P-glycoprotein

A study performed in cellular models indicates that GJ significantly activates p-glycoprotein mediated reduction in bioavailability, partially counteracting the CYP3A4 inhibitory effects of GJ.42 This experiment was performed in laboratory (CaCo-2) cell cultures, and was not a human trial. The results of this experiment were later found to be due to a laboratory artifact and were retracted132, though the retraction was not published by the original author. Subsequent results indicate that GJ likely acts as a weak p-glycoprotein inhibitor.

Start of New ArticleA recent study using GJ and digoxin shed further light on p-glycoprotein effects in humans. In a randomized crossover fashion, 12 healthy volunteers (7 male, 5 female) were given a single oral dose of digoxin 0.5 mg with either water or 250 mL of SSGJ 30 minutes prior to the dose, and 3.5, 7.5 and 11.5 hours after the dose. A two-week washout between study periods was employed.

Compared to the water group, mean peak blood concentrations (Cmax) rose 21%, time to peak level (Tmax) rose 8%, and total drug exposure at 48 hours (AUC48) rose 9%. None of these changes were statistically significant. AUC at 4 and 24 hours also rose 9% and this was considered statistically significant.

The authors consider GJ a weak inhibitor of P-glycoprotein, since studies with other known P-glycoprotein inhibitors show larger increases in digoxin AUC. They concluded that the study did not support the role of GJ as an important P-glycoprotein inhibitor, and that the modest increases in digoxin concentrations observed did not require any recommendations to alter digoxin dosing or titration when taken with GJ.114

Start of New ArticleIn a similar study, 7 healthy volunteers (4 male, 3 female) received a single oral dose of digoxin 1 mg with with either water or GJ in a randomized crossover design. A washout of two weeks between study periods was employed.

During the GJ phase, 240 mL of SSGJ was consumed 3 times daily for 5 days prior to digoxin administration, and 6 days after digoxin administration, in an attempt to maximize the effect on p-glycoprotein.

Compared to water, administration of digoxin with GJ showed peak blood levels (Cmax) decreased by a mean of 16%, total drug exposure (AUC) increased 3%, Time to peak concentration (Tmax) increased 25% and half-life was essentially unchanged (decreased by 3%). None of these changes were determined to be statistically significant, although significant interindividual variability was observed.

The authors concluded that when results are taken with the previous study, GJ ingestion does not have a significant effect on intestinal P-glycoprotein activity, and that P-glycoprotein inhibition does not play an important role in grapefruit interactions.115

Seville Orange Juice

Start of New ArticleA trial of administration of cyclosporine with GJ and Seville orange juice, both of which contain 6',7'-dihydroxybergamottin, was conducted recently. 7 healthy volunteers were given either water, single-strength GJ, or Seville orange juice 30 minutes prior to a 7.5 mg/kg dose of cyclosporine (Sandimmune® brand) in a randomized crossover design. The effect of Seville orange juice on CYP 3A4 concentrations in 2 individuals (via duodenal biopsy) and the effect of 6',7'-dighydroxybergamottin on p-glycoprotein activity in vitro were also assessed. The AUC for cyclosporine was increased 55% with GJ, whereas Seville orange juice did no significantly affect the AUC of cyclosporine. The two individuals who had duodenal biopsy showed clearly decreased enterocyte concentrations of CYP 3A4, suggesting that 6',7'-dihydroxybergamottin is not solely responsible for the increased cyclosporine levels when given with GJ. The in vitro studies confirmed that 6',7'-dihydroxybergamottin had no effect on p-glycoprotein.

So, if the two juices had similar concentrations of 6',7'-dihydroxybergamottin, why did cyclosporine blood levels increase with GJ, but not with Seville orange juice ? P-glycoprotein is known to play a significant role in cyclosporine availability, and based on this study, and in agreement with the study listed above, it is reasonable to conclude that GJ contains a compound or compounds that inhibit P-glycoprotein activity, which are not found in Seville oranges. Further studies are needed to identify inhibitors of p-glycoprotein in GJ and to evaluate the relative contribution of reduced p-glycoprotein and CYP 3A4 activity to the increased oral bioavailability of other drugs.51 Seville oranges may selectively "knock out" CYP 3A4 activity, while the inhibitor(s) of p-glycoprotein in GJ appear to be different from those compounds identified as inactivating CYP 3A4.132

Start of New ArticleEleven healthy volunteers (6 male, 5 female) received 30mg dextromethorphan daily for 5 days with either 200 mL single-strength GJ (study day 2), 200 mL seville orange juice (SOJ) (study day 4), or water (study day 1, 3, 5) in a linear, non-crossover fashion. Immediately, the non-crossover design raises a concern, since the effect of GJ on the enzymes is known to persist for 72 hours or more. A 3 -day washout was given after study day 2, and at least 7-days passed between study day 2 and 4. Blood levels were not collected in this study. Urine point assays, and 8-hour total urine concentrations were used to determine dextromethorphan availability in a complicated series of analyses, based partially on animal data, and some assumptions.

The fraction of the administered dose of dextromethorphan that escaped first pass metabolism were found to increase significantly and similarly when GJ or SOJ were taken with dextromethorphan on study days 2 and 4, although lack of an adequate washout period after GJ intake on day 2 was provided, the administration of SOJ with dextromethorphan produced an identical effect on the dextromethorphan pharmacokinetic profile as was observed with GJ. Two volunteers experienced drowsiness, but were found to be CYP 2D6 "poor metabolizers" (the alternate metabolic pathway for dextromethorphan and its metabolites). It also appears that both GJ and SOJ affected p-glycoprotein transport protein activity.94

Start of New ArticleTen healthy volunteers (5 male, 5 female) received a dose of felodipine 10mg with 240 mL of either fresh squeezed Seville orange juice, commercial orange juice, or grapefruit juice (diluted to contain the same total molar concentration of bergamottin and 6'7'-dihydroxybergamottin as the Seville orange juice). This study was conducted in randomized crossover design with at least a 7 day washout between study periods.

Seville orange juice increased felodipine AUC 76% and Cmax was increased 61%, compared to commercial orange juice (control). As expected, grapefruit juice increased felodipine AUC by 83% with Cmax increased 88%

An additional CYP 3A4 inhibitor, bergapten was found in seville orange juice, but not in grapefruit juice. Bergapten appears to have 1/3 the potency of 6'7'-dihydroxybergamottin when tested with midazolam in intestinal cell concentrations.132

Pomelo & Other Related Citrus Fruits

Start of New ArticleA case report exists of an interaction between tacrolimus and pomelo (also known as pummelo), a grapefruit-related citrus fruit. A patient taking tacrolimus post-renal transplant was stabilized on a tacrolimus dosage of 6 mg/day with tacrolimus blood levels stable in the therapeutic range of 8-10 ng/mL. A subsequent check of the tacrolimus level was increased at 25.2 ng/mL. The patient had no subjective symptoms. Upon further questioning, it was revealed that he had consumed approximately 100g of pomelo from his garden just prior to the tacrolimus on the day before blood sampling for tacrolimus level determination.117

Start of New ArticleFollow up testing by the above authors confirmed that some forms (1 of 3 tested) of pomelo juice extract were as potent inhibitors of CYP 3A4 as grapefruit juice extract in vitro. The pomelo extract had little effect on p-glycoprotein in a cellular model.124

Start of New ArticleIn 2004, Japanese researchers developed an enzyme-linked immunosorbent assay specific for coumarin derivatives that contain the geranyloxy- side chain, known to be the chemical moiety in grapefruit responsible for CYP3A4 inhibition. This allowed other fruits to be screened for containing 6'7'-dihydroxybergamottin.

Of 15 fruits screened, white grapefruit (control), red pummelo (pomelo), sweetie (oro blanco), melogold, banpeiyu pummelo, hassaku orange, sour (seville) orange, lime and natsudaidai showed significant immunoreactivity, indicating the presence of furanocoumarin derivatives. Navel orange, sweet orange and yuzu showed slight immunoreactivity, while iyokan orange, satsuma mandarin, ponkan mandarin and dekopon mandarin showed minimal immunoreactivity.

The researchers noted that besides the Rutaceae family (grapefruit-like) many plants of other families such as Umbelliferae, Leguminosae and Moraceae also contain furanocoumarin derivatives. Many plants of these families are used as common vegetables or traditional medicines, and it is possible that furanocoumarin derivatives contained in these plants could change the pharmacokinetics of certain drugs.129

Start of New ArticleIn a related study, Japanese researchers performed in vitro testing of local citrus fruits by incubating citrus fruit residue with human liver extract, midazolam, and measuring residual CYP 3A activity. Fruit juice residues prepared from banpeiyu pummelo, hassaku orange, takaoka-(suisho) buntan pummelo and kinkan (Tamatama) inhibited microsomal CYP 3A activity. Banpeiyu pummelo inhibition was strongest, though weaker than the white grapefruit control. No significant CYP 3A inhibition was noted with ama-natsu orange, dekopon mandarin, hyuga-natsu orange, unshu-mikan (satsuma mandarin) or navel orange. These findings are in agreement with the above study which looked at enzyme-linked immunoreactivity testing.130

Start of New Article In another related study by Japanese researchers, in vitro testing of tropical fruits was performed by incubating citrus fruit residue with human liver extract, midazolam, and measuring residual CYP 3A activity. Residues prepared from star fruit, pomegranate, and common papaw significantly inhibited CYP 3A activity. In all three cases, inhibition was stronger than the white grapefruit control. No significant inhibition was noted with valencia orange, mango, rambutan, kiwi fruit, dragon fruit or passion fruit.131

Time course of GJ-drug Interactions

Start of New ArticleA research group conducted a study with simvastatin to characterize the duration of the GJ induced CYP 3A4 inhibition. Ten healthy volunteers (9 male, 1 female) received simvastatin 40 mg with either water as a control, and either 0, 1, 3 or 7 days after drinking high-dose GJ (200 mL double-strength GJ) three times daily for 3 days in a non-randomized crossover fashion. As seen with the previous study, significant increases in simvastatin levels after GJ intake were observed on the day 0 study when compared with water. Simvastatin AUC was increased 1250%, with Cmax increased 1104%. Time to peak concentration (Tmax) was also prolonged from 2 hours to 4 hours (100% increase). This effect was significantly reduced if 24 hours elapsed between the last GJ intake and simvastatin dosing. At this time, simvastatin AUC was increased 105%, and Cmax was increased 136%. The authors noted that the effect of even high-dose GJ 24 hours after ingestion is only about 10% of that seen with concurrent GJ and simvastatin intake. AUC and Cmax of simvastatin when taken on day 3 and day 7 after last GJ intake were not significantly elevated compared to control, indicating that the interaction potential of even high amounts of GJ intake dissipates within 3-7 days after last GJ ingestion.

This is useful for characterizing the time course of GJ-drug interactions, and fits with prior expectations that the GJ effect can last up to 3 days after last GJ ingestion.90

Cont/... http://www.powernetdesign.com/grapefruit/general/mechanism.html

Many suffer from the inability to metabolize compounds from meds, foods, detergents, solvents, air pollution and so forth. The proposed theory concerns liver pathways. Other related mechanism includes the NO-ONOO theory from Dr Pall, NMDA, vanilloid, and TRPV receptors. Lack of digestive enzymes, dysfunctional pancreas, and detoxification pathways.

Although it advises eating certain foods, such as broccoli for instance, many cannot eat most foods. Likewise, it advises taking oxidants, which risk turning pro-oxidants.

See article below:

This document was provided by
Continuum Magazine
VOL. 5 No. 1

Once thought to be the seat of courage, love etc., the liver is central to our bodies’ endless process of removing unwanted chemicals. Leading British nutritionist and Director of the Society for the Promotion of Nutritional Therapy LINDA LAZARIDES takes a closer look.

One of our body’s most vital functions is to convert metabolic products and toxins into safe, soluble substances which can be eliminated via the urine or the gall bladder into the intestines. The liver plays an all-important role in this process – known as detoxification or biotransformation. Recent research has shown that many patients with chronic illnesses have a disordered liver biotransformation ability.

We simply don’t know all the diseases and health disorders which may be promoted by a toxic overload resulting from such dysfunction, but progress is beginning to be made in looking at specific detoxification pathways and relating underfunctioning of these to the development of disease.

Pathways

A number of biochemical ‘pathways’ – sequences of chemical changes – are involved in liver biotransformation. These are normally grouped into oxidation, reduction or hydrolysis reactions (Phase I) and conjugation reactions (Phase II). Phase I reactions are catalysed by a group of liver enzymes scientifically known as cytochrome P450 oxidases (or P450 oxidases or cytochrome p450s). These enzymes introduce oxygen into the chemical structure of toxins or metabolites. Typically, by this process the toxins are converted into intermediate substances – alcohols and aldehydes – then into acids, which are water-soluble, and can be excreted via the urine.

Phase I detoxification

The intermediate substances created during Phase I detoxification, which include – far more so than the original toxins. Their harmful effects are primarily controlled by antioxidant nutrients/enzymes: a plentiful supply of these substances is essential. Apart from free radicals, intermediate metabolites include chloral hydrate (which is identical to the knock-out drug often known as a ‘Mickey Finn’), epoxides, and endogenous benzodiazepines – substances similar to Valium and other tranquillisers and sleeping pills. This makes it easier to understand how chronic fatigue, for instance, can develop when a toxic overload is present.

The more P450 enzymes are induced in the liver, the more of the toxic intermediates will be present in the body. P450 enzymes are induced by caffeine, alcohol, dioxin and other pollutants, exhaust fumes, high protein diets, oranges and tangerines, organophosphorus pesticides, paint fumes, steroid hormones, and a variety of drugs including paracetamol (acetaminophen), diazepam tranquillisers and sleeping pills, the contraceptive pill and cortisone.

Aldehydes

Substances which can inhibit the action of P450 enzymes include carbon tetrachloride, carbon monoxide, barbiturates, quercetin and naringenin (found in grapefruit). The oxidation reaction can also be blocked by an excess of toxic chemicals, a lack of enzymes, lack of nutrients and/or loss of oxygen. Cant tolerate any of those either.

Such blocking results in a build-up of more toxic substances such as formaldehyde and other aldehydes in tissue. This can in turn lead to a spreading phenomenon, with increasing sensitivity to more chemicals such as ketones and alcohols, and eventually even to natural chemicals occurring in foods, pollen and mould. A build-up of aldehydes can in severe cases lead to tissue cross-linking, causing vasculitis with possible seizures and brain damage.

Although most aldehydes in the body are thought to occur as intermediate metabolites, external sources include exposure to formaldehyde gas (which is given off by new carpets, curtains and other furnishings) and breakdown products of ethylene glycol and methanol.

Two known sources of aldehydes are intestinal overgrowth with Candida albicans, as well as the peroxidation of polyunsaturated fats. The fatigue, foggy thinking and ‘brain fag’ linked with candidiasis may be due to an overloading of the detoxification system with aldehydes, which can even lead to a reverse reaction of aldehyde to alcohol. Extreme intolerance to alcohol consumption may occur in these individuals, as it does in those diagnosed with ME or chronic fatigue syndrome.

Amines

Cytochrome P450 and other oxidizing enzymes also oxidize amines such as phenylethylamine found in chocolate, tyramine found in cheese, and adrenaline, noradrenaline and dopamine. These are oxidized into aldehydes by the enzyme mitochondrial monoamine oxidase (MAO) – if this enzyme is blocked, for instance by MAO inhibitor drugs used to treat depression, tyramine, for instance, cannot be metabolized and hypertension can develop as a chemical sensitivity reaction.

Phase II detoxification (conjugation) There are five main conjugation categories, including acetylation, acylation (peptide conjugation with amino acids), sulphur conjugations, methylations and conju-gation with glucuronic acid. Some substances enter Phase II detoxification directly, others come via Phase I pathways.

Conjugation involves the combining of a metabolite or toxin with another substance which adds a hydrophilic (or water-reactive) molecule to it, converting lipophilic (or fat-reactive) substances to water-soluble forms for excretion and elimination. Individual xenobiotics and metabolites usually follow a specific path, so whereas caffeine is metabolized by P450 enzymes, aspirin-based medications are conjugated with glycine, and paracetamol with sulphate.

Acetylation

Acetylation requires pantothenic acid to function. It is the chief degradation pathway for compounds containing aromatic amines such as histamine, serotonin, PABA, P-amino salicylic acid, aniline and procaine amide. It is also a pathway for sulphur amides, aliphatic amines and complex hydrazines.

A proportion of the general population – perhaps up to 50 per cent – are slow acetylators. This rises to as high a level as 80 per cent among the chemically sensitive population. Their N-acetyltransferase activity is thought to be reduced, and this prolongs the action of drugs and other toxic chemicals, thus enhancing their toxicity.

Acylation

Acylation uses acyl CO-A, with the amino acids glycine, glutamine and taurine. Conjugation of bile acids in the liver with glycine or taurine is essential for the efficient removal of these potentially toxic compounds. Disturbed acylation by pollutant overload decreases proper levels of bile in the gastrointestinal tract, resulting in poor assimilation of lipids and fat-soluble vitamins, and disturbed cholesterol metabolism.

Toluene, the most popular industrial organic solvent, is converted by the liver into benzoate, which like aspirin must then be detoxified by conjugation with the amino acid glycine (glycination): large doses of glycine and N-glycylglycine are used in treating aspirin overdose. Benzoate itself is present in many food substances and is widely used as a food preservative.

Glycine is a commonly available amino acid, but the capacity to synthesize taurine may be limited by low activity of the enzyme cysteine-sulfinic acid decarboxylase. Damage can occur to this enzyme directly by pollutants, or by overload/over-use resulting in depletion.

Both taurine- and glycine-dependent reactions require an alkaline pH: 7.8 to 8.0. Environmental medicine specialists may alkalinize over-acidic patients by administering sodium and potassium bicarbonate in order to facilitate these reactions.

Glutathione conjugation, using the amino acid glutathione in its reduced form, is used for the transformation of xenobiotics such as aromatic disulphides, naphthalene, anthracene, phenanthacin compounds, aliphatic disulphides – and the regeneration of endogenous thiols from disulphides. There is a cycle of replenishment for glutathione, allowing it to be reformed after conversion to glutathione reductase. Heavy metals can inhibit this cycle, thus preventing replenishment.

Sulphur conjugation (sulphation)

Neurotransmitters, steroid hormones, certain drugs and many xenobiotic and phenolic compounds such as oestrone (one of the forms of oestrogen), aliphatic alcohols, aryl amines and alicyclic hydroxy-steroids employ sulphation as their primary route of detoxification. Steventon at Birmingham University (UK) has found that many sufferers from Parkinsonism, motor neurone disease and Alzheimer’s disease as well as environmental illness, tend to have a reduced ability to produce sulphate from the amino acid cysteine in their body, and instead accumulate cysteine.

Sulphate may be ingested from food, but is also produced by the action of the enzyme cysteine dioxygenase on cysteine. This process is known as sulphoxidation.

The body’s ability to conjugate toxins with sulphate is ‘rate limited’ by the amount of sulphate present; if there is inadequate sulphate, toxins and metabolites can accumulate, perhaps building up to levels which cause degeneration of nervous tissue after several decades.

Steventon’s findings are a matter for serious concern. How many individuals are given the opportunity to find out whether they are poor sulphoxidizers and to reduce their chances of developing the above mentioned diseases by improving their sulphoxidation ability?

Methylation

According to environmental medicine specialist William Rae, the process most often disturbed in chemically sensitive people involves methylation reactions catalysed by S-adenosyl-L-methionine-dependent enzymes. Methionine is the chief methyl donor to detoxify amines, phenols, thiols, noradrenaline, adrenaline, dopamine, melatonin, L-dopa, histamine, serotonin, pyridine, sulphites and hypochlorites into compounds excreted through the lungs. Methionine is needed to detoxify the hypochlorite reaction.

The activity of the methyltransferase enzyme is dependent on magnesium, and, due to the frequency of magnesium deficiency, supplementation with this nutrient will often stabilize chemically sensitive patients.

Glucuronidation

Glucuronic acid is a metabolite of glucose. It can conjugate with chemical and bacterial toxins such as alcohols, phenols, enols, carboxylic acid, amines, hydroxyamines, carbamides, sulphonamides and thiols, as well as some normal metabolites in a process known as glucuronidation.

For most individuals glucuronidation is a supplementary detoxification pathway. It is a secondary, slower process than sulphation or glycination, but is important if those pathways are diminished or saturated. Obese people seem to have an enhanced capacity to detoxify molecules that can use the glucuronidation pathway. However, damage to the capacity for oxidative phosphorylation which takes place in the mitochondria, is likely to diminish the capacity for glucuronide conjugation.

Overload

If the liver’s detoxification pathways are excessively stimulated and overly utilized, they eventually become depleted or begin to respond poorly – being suppressed by toxic chemicals. Once breakdown of the main pathways occurs as a result of pollutant overload, toxins are shunted to lesser pathways, eventually overloading them, and disturbing orderly nutrient metabolism. Chemical sensitivity may then occur, followed by nutrient depletion and finally fixed-name disease. Depleted immunity is also a potential outcome of a toxic overload.

Interesting facts

• Dr William Rae of the Environmental Health Centre in Dallas says that the most severely ill chemically sensitive patients not only have abnormally low antipollutant enzymes, in addition to toxic suppression and nutrient depletion, but in some instances antibodies are produced against cytochrome P450 and these may inhibit or decrease its effectiveness.

• Environmental medicine specialists have found that almost 35 per cent of chemically sensitive patients are deficient in intracellular sulphur. Not only can this hinder the detoxification of some sulphur-containing and other toxic chemicals, it can enhance the harmful effects of exposure to cyanide from foods such as cassava and almonds as well as from tobacco products. The hereditary disease known as Leber’s optic atrophy involves a defect in the ability to detoxify cyanide, and leads to sudden, permanent blindness on first exposure to cyanide in small amounts such as those ingested from smoking cigarettes.

• Many multimineral supplements in the UK omit iron and copper due to theories that individuals may already be overloaded with these nutrients. However if no overload is present, an unbalanced supplement may promote depletion of the minerals. The Environmental Health Centre in Dallas finds that intravenous infusions to replenish iron stores brings dramatic improvements for the chemically sensitive patient as part of their detoxification process. Copper is also found to help catalyse the cytochrome systems. (NB: self-supplementation with iron and copper should be cautious, to avoid iron and copper overload conditions).

• Although the liver is the primary site for oxidation of xenobiotics, the cytochrome P450 system is found in other tissues that are exposed to environmental compounds like the skin, lungs, gastrointestinal tract, kidneys, placenta, corpus luteum, lymphocytes, monocytes, pulmonary alveolar macrophages, adrenals, testes and brain, in both the mitochondria and in the nuclear membrane.

• Always rinse your washing-up carefully. Pollutants in the form of solvents and detergents can damage and penetrate cell membranes and damage the contents of the cell.

• Vitamin B3 has been shown to accelerate the clearance of aldehydes in some chemically sensitive patients.

• Molybdenum, although an essential element, competes with sulphate in its activation step to the important enzyme PAPS and can thus lower sulphate levels and impair sulphation ability. Environmental medicine experts warn that molybdenum supplementation may be contraindicated in individuals with poor sulphation ability.

• The substance naringenin, found in grapefruit, can significantly inhibit Phase I detoxification, as can grape-fruit itself. This may prove clinically useful in some situations where Phase I activity is too high, (as shown in liver function tests available from nutritional therapists).

• Persons who have been exposed to toxic chemicals, drugs and other xenobiotics, have increased requirements for some vitamins. Functional nutritional assays for vitamins B1, B2, B3, B6, B12 and folate, and serum levels of vitamins A, D, C and beta carotene were performed in a random sample of 333 environmentally-sensitive patients prior to treatment. 57.8% were found to be deficient in B6, 37.7% in vitamin D, 34.9% in B2, 32.2% in folate, 27.7% in vitamin C, 21.4% in niacin, 14.9% in B12, 5.6% in vitamin A and 4.6% in beta-carotene. (Ross GH et al: Evidence for vitamin deficiencies in environmentally-sensitive patients. Clinical Ecology 6(2):60-6, 1989.)

Adapted from the Nutritional Health Bibleby Linda Lazarides (Thorsons, £9.99). Published September 1997. Available from all good bookshops or by mail order from SPNT Books (see address below).
Foods to aid detoxification

Beetroot helps with liver drainage

Broccoli, cauliflower and other cruciferous vegetables these aid cytochrome P450 activity

Protein

Radish, watercress rich in sulphur.
Supplements to aid liver detoxification

B complex vitamins

Digestive enzymes may be necessary to ensure that protein is adequately digested and glycine is readily available

Essential fatty acids

N-acetyl cysteine (NAC)

Reduced glutathione

Selenium, zinc, magnesium and manganese possibly iron and copper if used with caution

Taurine (a useful combination product is magnesium taurate)

Vitamins C and E and beta carotene.
Liver herbs to aid detoxification

(traditionally known as ‘blood cleansing’ herbs)

Dandelion root cholagogue (stimulates liver secretions and bile flow)

Globe artichoke leaf promotes regeneration of the liver and promotes blood flow in that organ

Silymarin according to recent research, this herbal extract stabilizes the membranes of liver cells, preventing the entry of virus toxins and other toxic compounds including drugs. Promotes regeneration of the liver.

Turmeric a cholagogue like dandelion, but may irritate the gastric mucosa. Its advantages are its cheapness and ability to be used in cookery.

These herbs are best combined with wild yam, which helps to prevent liver spasms caused by gall bladder stimulating herbs.

For help with a liver detoxification programme, it is best to consult a nutritional therapist, who can arrange for (non-invasive) tests to determine which pathways need boosting.

For a list of nutritional therapists and other natural medicine practitioners in your area, send £1 plus sae to: Society for the Promotion of Nutritional Therapy (SPNT), PO Box 47, Heathfield,
Glossary

acetylation – combination with acetic acid

alveolar macrophages – rounded granular phagocyte cells in the alveoli of the lungs that ingest inhaled particulate matter

aldehydes – a class of organic compounds containing the atomic group C(Carbon)H(Hydrogen)O(Oxygen)

amines – organic compounds containing nitrogen

amino acids – the chief constituents of proteins; the “building blocks” of life

biochemical pathway – a series of chemical enzyme reactions, that converts one biological material into another

Candida albicans – a quite common fungus in humans, which when unchecked can cause illness

catalyse – speeding up of a chemical reaction by a substance which remains after the reaction

conjugation – the joining together of two compounds to form another

corpus luteum – a yellow glandular mass in the ovary

dioxins – a group of chemicals present as trace contaminants in herbicides

endogenous – arising from within the organism

epoxides – compounds containing one oxygen atom bound to two different carbon atoms

ethylene glycol – a solvent used as an antifreeze

gall bladder – the reservoir for bile, on the surface of the liver

hydrolysis – the splitting of a substance’s molecules by adding water (H 2 0): a hydrogen-oxygen molecule (HO-) being added to one fragment, and the hydrogen atom (H) to the other

hydrophilic – readily interacting with water

intracellular – within cells

ketones – a class of organic compounds containing the molecule C=O

lipids – fats and fat-like substances

lipophilic – readily reacting with fat

lymphocytes – an immune-system cell generated by lymph tissue

metabolic, -ism – all the processes which create and maintain, and use up, organised living matter

metabolites – any substance produced by metabolism

methanol – a solvent

methylation – the addition of a methyl, i.e. a molecule of C(Carbon) and three H(Hydrogen) atoms

mitochondria – small cell organelles, with their own nucleic acids, that through synthesis of adenosine triphosphate (ATP) produce most of the energy for cells

monocytes – cells formed in bone marrow that travel to tissues, e.g. lungs and liver, to develop into macrophages

oxidation – the removal of electrons from the atoms of a substance; often by combination with oxygen

pantothenic acid – a member of the vitamin B complex

peptide – a compound of more than two amino acids

peroxidation – a chemical reaction creating an oxide with more oxygen than any other

polyunsaturated – denoting a chemical compound, particularly a fatty acid, having two or more double or triple bonds in its hydro-carbon chain

reduction – the addition of electrons to the atoms of a substance; often by combination with hydrogen

thiol – the univalient – S(sulphur)H(hydrogen) group

vasculitis – inflammation of a (usually blood) vessel

xenobiotics – substances foreign to the body