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Effects of Oral Zinc Supplements on Serum, Hair and Sweat Zinc Levels in 7 Subjects

Davies S

Preliminary evidence is presented on the basis of pre- and post- zinc supplementation zinc studies of seven patients, that suggests that sweat zinc measurements may be a useful adjunct in the clinical assessment of zinc status and may be a more sensitive index than either serum or hair zinc levels.

A New Functional Test of Manganese Status

Hunnisett A, Howard J, Davies S
J. Nutr. Med. 1990;1:209-215

There is limited clinical interest in the role of manganese in the pathogenesis and therapy of disease despite the fact that some research has shown it to be an important trace mineral. One of the reasons for this may be the difficulty in the accurate measurement of Mn concentration in biological fluids with the expertise and expense required. A functional test for Mn status is described based upon the activation of isocitrate dehydrogenase by Mn. The results obtained from this test are compared with more conventional indices of Mn status, i.e. serum and sweat concentrations. The possible limitations are discussed along with its advantages as a simple and inexpensive screening test.

Abnormalities in Essential Amino Acids in Patients with Chronic Fatigue Syndrome

Eaton KK, Hunnisett A
J. Nutr. Med.1991;2:369-376

A laboratory study was performed comparing the patterns of urinary amino acid excretion in patients with chronic fatigue syndrome (CFS) with a control group of subjects without fatigue or allergy. Fifteen out of 21 patients in the CFS group showed abnormal patterns with both reduced and increased excretion of some acids. In contrast, the control subjects showed only increased excretion of some acids, and a finding present in only four out of 20 subjects.

Abnormal Gut Fermentation: Laboratory Studies Reveal Deficiency of B Vitamins, Zinc and Magnesium

Eaton KK, McLaren-Howard J, Hunnisett A, Harris M
J. Nutr. Biochem. 1993;4:635-638

Gut fermentation in the colon is a normal phenomenon whereby soluble non-starch polysaccharides are metabolised to short-chain fatty acids. Abnormal fermentation may be associated with clinical symptoms and is generally assumed to take place in the small bowel. It may be established by ethanol production after a sugar challenge in the fasting subject, which produces maximum production of ethanol 1 hour after sugar challenge. This timing is compatible with the dose acting in the small bowel, but not the large. It was noted that patients with abnormal gut fermentation established by gut fermentation ethanol production tests tended to have low levels of vitamins and minerals, and it was therefore decided to make a prospective study of patients with the condition to determine if this was so.

Patients were tested for ethanol production together with standard functional analysis techniques for vitamins B1, B2 and B6 and zinc and magnesium concentrations by sweat analysis using air/acetylene flame atomic absorption. Fifty normal subjects (group A) were analysed against 30 positive patients by alcohol testing (group B). Statistical analysis, using the Wilcoxon Sum of Ranks test, revealed a remarkable and consistently high difference for vitamins and minerals between the two groups. In group B, 19 of 30 patients had four of five or five of five nutrients abnormal, and no subject with a positive alcohol test had less than two abnormal nutrients.

It is concluded that the syndrome that causes abnormal gut fermentation appears to have adverse effects on levels of B vitamins, zinc and magnesium. As yet it is not clear whether this is a result of malabsorption, over-utilization, or excessive excretion. The level of ethanol production in this condition is low, but the presence of the nutritional deficits implies that the syndrome may cause quite significant adverse effects on health. More research in this area is required to replicate and extend these studies.

Sweat Lead Levels in Persons with High Blood Lead Levels: Lead in Sweat of Lead Workers in the Tropics

Omokhodion FO, Howard JM
Sci. Tot. Env. 1991; 103:123-128

Samples of blood, sweat and urine were collected from eight control subjects and 19 lead workers in a battery manufacturing factory in the tropics. Sweat samples were collected while workers cycled on a bicycle ergometer at room temperature (27-31C). All samples were analysed by atomic absorption spectrophotometry. Workers with blood lead levels of 13-36g/dl had sweat levels of 72-256g/l and urinary levels of 28-288g/g creatinine, while controls had levels of 9-12.2g/dl, 9-30g/l and 9-19.6g/g creatinine, respectively. Estimations of sweat lead in lead workers can be masked by skin contamination.

Trace Elements and Vitamins Efficiency in Alcoholic and Control Subjects

Christopher C H Cook, Richard J Walden, Barrie R Graham, Carola Gillham, Stephen Davies and Brian N C Prichard
Alcohol & Alcoholism, 1991;26;5/6:541-548

A wide range of trace elements and vitamins was studied in alcoholic patients admitted for detoxification and in healthy controls. Alcoholic subjects were found to be deficient relative to controls in magnesium and vitamin E, while a relative excess of serum iron and copper, and sweat nickel, was noted. A surprisingly wide range of deficiencies , as compared with standard laboratory ranges, was seen in the control group. This finding emphasizes the need for adequate control groups in nutritional studies of alcoholism, the insufficiency of an adequate diet alone to guarantee adequate nutrition, and the likely high prevalence of undetected nutritional deficiency in the general population. Further research is required on the clinical benefits of nutritional supplementation as part of the treatment of alcoholism, and the value of conventional supplements as a routine treatment is questioned.

Osteoporosis, Alkaline Phosphatase Isoenzyme
Measurements and the Effect of Nutritional

Presented at the 3rd Bath Conference: Osteoporosis and Bone Mineral Measurement, 23-26th June 1992. In: Current Research in Osteoporosis and Bone Mineral Measurement II.

Ed.: EFJ Ring, British Institute of Radiology, London, 1992.

A series of organ derived isoenzymes of alkaline phosphatase (EC ALP) are present in blood serum. The activity of bone ALP is increased during bone development in children and in and in healing fractures as well as in a variety of bone diseases. Total ALP remains normal in osteoporosis.

Magnesium is involved in suppressing parathyroid hormone and in stimulating calcitonin. Manganese is essential for bone growth and it interacts with oestrogens. Zinc is essential for bone formation and deficiencies are associated with bone loss as well as reduced ALP activity. Copper status affects bone resorption and severe vitamin C deficiencies are associated with osteoporosis. Boron may minimise osteoporosis possibly by incresing endogenous oestradiol.

We have measured nutrients related to bone metabolism as well as total and bone ALP in five small groups of women before and after six weeks of nutritional supplementation. The tests were repeated after a further six weeks during which boron was added to the supplement programe. The groups were: 1) 5 controls, 2) 4 menstruating women with two or more nutrient deficiencies, 3) 4 post-menopausal women with no evidence of osteoporosis and 5) 3 post-menopausal women on hormone replacements.

Much lower bone ALP levels and quite marked nutrient deficiencies were demonstrated in the osteoporotic women. The levels normalised with nutritional supplementation except in one of the women on HRT whose bone ALP remained low. It was not possible to deduce from our results whether there was a further beneficial effect when boron was added to the supplement programme.

The mean bone ALP levels were as follows:

Group1Group 2Group 3Group 4Group 5
Initial result51.644.542.035.023.0
6 weeks supplementation52.452.551.853.836.7
12 weeks supplementation 57.858.857.063.040.0

( laboratory reference range 35 90)

It seems very likely that the prevalence of nutritional deficiencies and the high incidence of osteoporosis are connected. We believe that further investigation of these interactions will increase the understanding of the metabolic basis of osteoporosis and, hopefully, lead to preventive measures and more adequate treatment.

Magnesium and Potassium Deficiencies in Women with Pre-menstrual Syndrome

Stewart A, Howard JMH

Magnesium deficiency has been described in women with Pre-Menstrual Syndrome (PMS). Measurement of serum and red cell magnesium levels in 17 women with severe PMS confirms the previous finding of an intracellular deficiency of magnesium.

Serum-Magnesium 0.748 0.05 mmol/L normal 0.6 1.2

Red Cell-Magnesium 1.67 0.08 mmol/L normal 1.7 2.6

Red Cell-Potassium 81.69 2.39 mmol/L, normal 80.5 95.6

A total 14 women had depressed red cell magnesium levels (14 subnormal). In addition red cell potassium levels were also depressed.

Deficiency of magnesium or magnesium and potassium may contribute to PMS. Measurement of these nutrients and correction of their deficiency may help to alleviate the symptoms of PMS.

Changes in Plasma Amino Acids during Conditioning Therapy prior to Bone Marrow Transplantation: Their Relevance to Antioxidant Status

Hunnisett A G, Kars A, Howard J, Davies S
Amino Acids 1993;4:177-185

Bone marrow transplant (BMT) recipients undergo a bimodal regimen of conditioning therapy, the precise prescription being dependent upon the primary disease of the individual patient. Generally, this treatment consists of chemotherapy and total blood irradiation prior to transplantation, although the latter may or may not be included in the regimen. We have investigated amino acid metabolism and oxidant status in a small series of BMT recipients before and after conditioning therapy.

Plasma amino acids were measured by HPLC on 10 BMT recipients prior to commencing conditioning therapy, and again one week later before transplantation. In addition some general nutritional parameters and antioxidant components were measured. A marked decrease in the plasma concentration of a number of amino acids, especially those concerned with antioxidants, was observed over the 7 days of conditioning therapy.

There is also a significant reduction in antioxidant capability, as reflected by measurements of glutathione and erythrocyte glutathione peroxidase (GSH-Px), which may have an influence upon post-transplant recovery and graft function. Such a reduction in antioxidant concentrations may also have an influence upon the erythrocyte and platelet support required post-grafting.

The data presented in this paper adds to the evidence for the conditional essentiality of some amino acids such as taurine and glutamine, and may support the case for specific antioxidant intervention treatment prior to, and/or after conditioning therapy together with monitoring antioxidant status during the post-grafting period.

Intestinal Dysbiosis A Review

McLaren Howard J
Complementary Therapies in Medicine, 1993;1:153-157

The importance to human health of the intestinal microflora has been more widely recognised in recent years. Ever-increasing environmental challenges (antibiotics, oral contraceptives, food additives) have contributed to the greater prevalence of disharmony in the ecology of the intestines (intestinal dysbiosis). The consequences of this appear to extend beyond the immediately obvious gastro-intestinal distress; evidence points to the influence of nutrient intake, intestinal permeability, and changes in levels of essential fatty acids as the root cause of a number of systemic disorders. Other studies have implicated intestinal candidiasis as a basis for conditions ranging from recurrent infections and immune breakdown to chronic fatigue. Patients who ferment dietary carbohydrate to ethanol can be identified using a simple clinical test which, when positive, may be strongly suggestive of yeast overgrowth.

Lipoperoxides as an index of free radical activity in bone marrow transplant recipients; preliminary observations

Hunnisett A G, Davies S, McLaren Howard J, Gravett P J, Finn M, Gueret-Wardle D
Presented at the Fourth Conference on Trace Elements in Medicine and Biology, Chamonix, France, April 5-9, 1993 (Full paper J Biol Trace Element res 1995;47:125-132)

It has been previously demonstrated that the conditioning therapy given to bone marrow transplant (BMT) recipients creates a high oxidant stress, resulting in a measured reduction in antioxidants such as glutathione peroxidase (GSH-Px), vitamin E and cell peroxide fragilities.

As part of a current intervention trial of antioxidant therapy (AOT) in BMT recipients, plasma malondialdehyde (MDA) concentration was measured to assess the degree of peroxidation and free radical activity. Measurements were performed before and after conditioning therapy, and then at weekly intervals after transplantation in 20 patients (10 controls and 10 AOT recipients). The MDA results were compared with concurrent measurements of more specific elements of the antioxidant pathways (GSH-Px, selenium and vitamin E).

In all case MDA concentration was significantly increased after conditioning compared with baseline levels (p<0.0001), an increase which correlated inversely with GSH-Px (r=-0.81, p<0.01). The MDA concentration fell gradually after conditioning in all patients. This fall was, however, more rapid in the AOT group when compared to the controls and paralleled the gradual return towards normal levels of the other antioxidants. The change in MDA concentration occurred faster than changes in other indices, suggesting that MDA might be a better index of overall free radical activity.

Although the patient numbers are small, there is some evidence to suggest that MDA may act as a prognostic marker. In 83% of the patients with a poor post-operative course and who eventually died, the MDA concentration was significantly higher than that in the successful transplants. Also the fall of MDA concentration either did not occur, or was much slower in this group of patients. This point is currently being investigated in a larger number of patients.

Red Cell Magnesium and Glutathione Peroxidase in Infertile Women Effects of Oral Supplementation with Magnesium and Selenium

McLaren Howard J, Davies S, Hunnisett A G
Mag. Res. 1994;7:49-57

Six women with a history of unexplained infertility or early miscarriage and who had failed to normalise their red cell magnesium (RBC-Mg) levels after four months of oral magnesium supplementation (600mg/day) were investigated for red cell glutathione peroxidase activity (RBC-GSH-Px) and were compared with six age-matched women with a history of unexplained infertility of miscarriage who did normalise their RBC-Mg levels on magnesium supplementation. The six non-normalisers had significantly lower (P<0.0001) RBC-GSH-Px levels than the six normalisers. After a further two months of 200g daily oral selenium as selenomethionine and oral magnesium supplements, all six women normalised their RBC-Mg (P<0.0001) and RBC-GSH-Px (P<0.0001) levels. All 12 previously infertile women have produced normal healthy babies all conceiving within eight months of normalising their RBC-Mg levels. The possible relevance of these findings to the medical treatment of infertility is discussed.

Preventive medical laboratory assessment (the Health Risk Profile) and the nutritional assessment of the cancer patient

Davies, S.
Presented at the World Congress on Cancer, Sydney, Australia. April 1994

Recent laboratory animal and human clinical and epidemiological studies demonstrate that a range of micronutrients play a protective role in a wide range of degenerative diseases including cancer. The various methods used in our laboratory for assessing an individuals nutritional status are discussed, including water soluble vitamins, carotenoids, vitamin E, amino-acids and essential fatty acids, as well as a range of functional tests of antioxidant status and susceptibility to peroxidation and the degree of lipoperoxidation.

Results are presented of a recent study on nutritional assessment and the effects of a rationalised parenteral feeding regime on biochemical nutritional parameters in patients undergoing bone marrow transplantation.

Also discussed are the potential liabilities of giving relatively high doses of zinc supplements to patients with malignancy, and the relationship between zinc and metallothionein induction in normal and malignant cells. A new method of evaluating metallothionein is described, as is its application in clinical practice in the management of cancer patients.

Urinary Beta Alanine Excretion is a Marker of Abnormal as well as Normal Gut Fermentation

Eaton K, Howard M, Hunnisett A
J. Nutr. Med. 1994;4:157-163

Normal gut fermentation is the process whereby non-starch-soluble polysaccharides are metabolised in the large bowel to provide nutrients. It is well represented in the literature. Abnormal fermentation however can also be present. A test for this demonstrates the production of trace amounts of ethanol, measurable in blood. Beta-alanine production, measured by urinary excretion, is associated with normal fermentation, but this study demonstrates that beta-alanine production may be a consequence of abnormal fermentation as well as normal. We consider that it may be an independent marker of the disease process.

Gut Permeability Measured by Polyethylene Glycol Absorption in Abnormal Gut Fermentation as Compared with Food Intolerance

Eaton K, Howard M, McLaren-Howard J
J. R. Soc. Med. 1995;88:63-66

Gut permeability has been studied in patients with either food intolerance or abnormal gut fermentation as well as in normal subjects. Permeability was measured by polyethylene glycol absorption, and the reasons for this choice of probe are discussed. Results show that both symptomatic groups have statistically very highly significant deviations from the normal (P<0.01), consisting of over-absorption, significant at molecular weights 242, 286, 330 and 374. Whilst both study groups were different from the normal they were not different from each other. The implication for these findings in the diagnosis and management of food intolerance and abnormal gut fermentation are discussed.

Effective Non Drug Treatment of Menstrual Disorders and Female Infertility

Davies, Stephen
Proceedings of Optimal Nutrition for the Family, Australian Council for Responsible Nutrition and Discipline of Nutrition and Dietetics, University of Newcastle, New South Wales, 25-26 June 1995, Terrigal NSW

Menstrual disorders, recurrent miscarriage and problems of infertility constitute a major and important part of modern medical practice. Generally these are treated medically with hormone preparations. This paper covers a number of ways in which certain of these problems can be addressed without necessarily having to resort to prescribing synthetic hormonal preparations.

Appropriate Testing Nutritional Status

Davies S, McLaren-Howard J, Hunnisett A, Howard M
Proceedings of Optimal Nutrition for the Family, Australian Council for Responsible Nutrition and the Discipline of Nutrition and Dietetics, University of Newcastle, New South Wales, 25-26 June 1995, Terrigal NSW

Nutritional assessment can be divided into three main categories: a) clinical signs and symptoms, b) dietary history to reveal risk of inadequate intake and c) laboratory testing. In this paper discussion is limited to laboratory testing. It should be borne in mind that clinical conditions may increase nutrient requirements and that there is substantial variation in requirements due to biochemical individuality (1). This has been discussed elsewhere (2,3). An excellent list of common clinical signs of specific nutrient deficiencies can be found in Werbachs superb monograph "Nutritional Influences on Illness" (4) and is covered elsewhere (5). When assessing specific nutrient status it should be borne in mind that seldom does a single nutrient deficiency occur more usually several occur together in the same individual because of poor nutrient intake, poor absorption or poor retention. Interestingly the most common symptoms encountered in general practice are also symptoms of nutrient deficiencies, such as vitamin B complex (fatigue, depression, anxiety, sleep disturbances etc.) muscle and joint aches and pains, irregular heart rhythms (magnesium, copper, manganese and calcium).

Micronutrient Interaction in the Management of Patients Following Bone Marrow Transpla

Hunnisett A G W
PhD Thesis, Oxford Brooks University, 1996

Bone marrow transplantation (BMT) is an accepted form of treatment for haematological malignancies. It is also being used increasingly as a rescue treatment for patients with advanced solid organ tumours whose own bone marrow has been destroyed by high doses of chemotherapy of radiotherapy used against the malignancy. Despite its widespread use, however, the overall success rates of BMT is still rather poor with many centres reporting survival figures of little more than 50%. Many of the problems associated with the procedure may arise from the use of high dose chemotherapy and total body irradiation used as a conditioning therapy prior to the actual marrow transplant. This thesis examines how conditioning therapy affects micronutrient concentrations and how the resultant changes might be addressed in various post-transplant treatment regimens.

A total of 33 patients were entered into the project. Prior to any form of treatment the patient group was compared to a normal population to assess any differences in nutrient concentrations between them. A wide variety of micronutrient assays were carried out pre-treatment, following conditioning therapy and at regular intervals over the post-transplant course of each patient. Following conditioning therapy, the patients were sequentially divided into 3 groups, a control group (Group 1) following the normal treatment protocols, a limited intervention group (Group 2) essentially having increased micronutrient levels added to the TPN feeding regimen and a high-dose antioxidant treatment group (Group 3) treated with high doses of antioxidants.

Marked abnormalities in micronutrient values were found following conditioning therapy which were improperly addressed by the then current post-operative feeding regimen. The abnormalities were particularly marked with respect to indices of free radical activity. The significance of these changes are discussed with respect to the clinical course of the patients, their overall survival and how the various post-transplant treatment regimens addressed the problems.

Metabolism Clinical and Experimental

VOL 46, NO 5 MAY 1997

Age-Related Decreases in Chromium Levels in 51,665 Hair, Sweat and Serum Samples From 40,872 patients - Implications for the Prevention of Cardiovascular Disease and Type II Diabetes Mellitus

Stephen Davies, John McLaren-Howard, Adrian Hunnisett, and Mark Howard

This report shows, for the first time using modern analytical techniques, highly significant age-related decreases in chromium levels in 51,665 hair, sweat and serum samples obtained from 40,872 patients referred by their physicians to an independent medical research clinic and laboratory (r = -.536 to -.762, p < .0001 for all correlations). Males were found to have significantly lower mean chromium levels than females (p < .05 to .0001). There was good correlation between chromium levels in hair, sweat and serum, (r = .536 to .729, p < .0001 for all correlations), indicating that hair and sweat chromium levels are valid additions to serum levels in assessing chromium status. Chromium measurements on sweat, hair and serum were performed using graphite furnace atomic absorption spectrophotometry. The influences that age-related decrease in chromium levels might have on increasing the risk of developing age-related impaired glucose metabolism, disordered lipid metabolism, coronary artery disease, arteriosclerosis, and type II diabetes mellitus are outlined, and the role that refined carbohydrates play in the development of compromised chromium status is presented.

(Metabolism 1997; 46:469-473)

Mercury from dental amalgam fillings: Studies on oral chelating agents

Hibberd A, Howard M, Hunnisett A.
J.Nutr & Env. Med., September 1998

Since the early nineteenth century, dentistry has relied mainly on amalgam (approximately 50% metallic mercury (Hg)) for filling teeth. Scientific research has shown that hg is constantly released from amalgams, mainly as Hg vapour (Hg ), which is inhaled, absorbed, metabolized to ionic Hg (Hg2 + ) and distributed throughout the body, mainly bound to proteins. Dental amalgam is the major source of the body Hg burden. Toxicological research on amalgam Hg has indicated deleterious effects on the immune, renal, reproductive and central nervous systems, and oral and intestinal bacteria. Results do not indicate that amalgam fillings are safe. Oral DL-2,3-dimercapto-succinic acid, magnesium salt (DMSA); 2,3-dimercapto-1-propane-sulphonic acid, sodium salt (DMPS); N-acetyl-L-cysteine (NAC) and potassium citrate B.P. (K Cit) were studied for Hg chelating ability in patients who had, or until recently had, amalgam fillings. Based on the increase in urinary Hg concentrations after single doses, compared with controls, the order of efficacy was: DMPS plus K Cit., NAC plus K Cit. and DMSA (each producing an increase of 163%), then in descending order, DMSA plus K Cit., DMPS, NAC and K Cit. Very significant (p<0.01) correlations were demonstrated between post-chelation urinary and post-chelation sweat Hg concentrations with all agents. Both these parameters may be good indicators of total body Hg burden. The advantages of employing combined chelating agents were examined and some clinically useful and convenient methods of assessing and reducing Hg burdens suggested.

Hormone Replacement Therapy (HRT) and Osteoporosis: Bone Enzymes and Nutrient Imbalances - A Short Review of the Literature and Preliminary Reports of Two Small Studies

Davies S, McLaren-Howard JMH, Grant E.
J. Nutr. & Env. Med., June 1998; 8: 129-138

Contrary to popular belief the available published evidence suggests that osteoporosis is not primarily due to deficiencies of either calcium or oestrogen but is related to deficiencies of key nutrients. Serum bone alkaline phosphatase (ALP) activity is a measure of bone formation. Tartrate-resistant acid phosphatase (TRAP) is a measure of bone resorption. Low serum ALP activity relates to reduced zinc, magnesium and manganese concentrations. ALP activity improves when these nutrients are supplemented, both in vitro and in vivo, but it appears that copper decreases serum bone ALP activity. Among women with confirmed or suspected osteoporosis, all those taking hormone replacement therapy (HRT) had abnormally high serum copper levels. Hormone takers also had significantly lower white cell zinc, lower red cell magnesium and lower serum bone ALP concentrations, and significantly higher mean serum phosphate levels, than other women with osteoporosis. Hormone takers had lower serum manganese, TRAP and vitamin C levels, and higher urinary excretion of zinc and hydroxyproline but these did not reach statistical significance. These results suggest that taking exogenous steroid sex hormones is associated with a reduction in essential bone nutrients and reduced bone formation. International incidence data show that fractures among women aged 35-65 years have increased dramatically in hormone prescribing countries, and evidence is presented to indicate that this may be mediated by reduction in essential nutrients for bone formation. This study indicates the need for further research directed towards establishing the relationship between status of those nutrients essential for maintenance of bone integrity and the development of osteoporosis.

Fungal-type Dysbiosis of the Gut: The occurence of fungal diseases and the response to challenge with yeasty and mould containing foods

Eaton KK, Howard M.
J.Nutr & Env Med. 1998; 8: 247-255

Patients with fungal-type dysbiosis of the gut whose symptoms had cleared were asked to fill up questionnaires concerning current and previous fungal diseases and the effects of re-introducing certain foods into the diet. In 84% symptoms had cleared on diet alone, the remaining 16 required anti-fungal therapy in addition to dietary intervention. When yeast extract, leavened bread, alcoholic drinks and mould-containing cheeses were serially re-introduced into the diet, over half the patients reported recurrence of symptoms with each of the foods, but the pattern varied with different patients, few reacting to all they tested. Many had, or had had, fungal diseases but no adequate published surveys of the prevalence of current or past fungal diseases were identified for comparison after a careful literature search. The implications of these findings are discussed.

Urinary Histidine Excretion in Patients with Classical Allergy (Type A Allergy), Food Intolerance (Type B Allergy) and Fungal Type Dysbiosis

Eaton KK. Howard M.
J. Nutr. Biochem. 1998; 9: 586-590.

Changes in histidine excretion reflect histidine conservation and thus the level of histamine secretion. Low levels were found in untreated patients with atopic (type A) allergy. However levels in food intolerance (type B allergy) and fungal-type dysbiosis were also low (p <0.001 for each group compared with non-allergic controls). There were no differences between the three groups. The biochemical and clinical significance of these findings is discussed.

Zinc Deficiency in Children with Dyslexia: Concentrations of Zinc and other Minerals in Sweat and Hair

Grant ECG, Howard JMH, Davies S, Chasty H, Hornsby B, Galbraith J
Brit. Med. J. 1988;296:607-609

Developmental dyslexia is estimated to affect about 10% of 10 year olds. Studies of mineral concentrations in hair have found that children with impaired learning and those with behaviour disorders tend to have higher concentrations of toxic metals, especially copper, lead and cadmium. Although animal studies have shown that zinc is essential for brain development and function, controversy has arisen about the extent and severity of zinc deficiency in clinical practice because a simple, reliable and sensitive test is not yet in routine use. Sweat zinc concentrations are decreased in zinc deficient states. They may be a more useful guide to clinical zinc deficiency than either hair or serum concentrations. Therefore we compared concentrations of minerals in sweat and hair in children with dyslexia and a control group.

Multiple Chemical Sensitivity: recognition and management. A document on the health effects of everyday chemical exposures and their implications


British Society For Allergy , Environmental and Nutritional Medicine, PO Box 7, Knighton, LD& 1WT, UK
J. Nutr. & Env. Med. 2000; 10: 39-84

We live in a chemical world and all human metabolism is chemical in nature. However, for purposes of this document the term chemical will be used to describe chemicals which do not contribute to normal metabolism mainly man-made synthesised chemical compounds and chemical pollutants . These may be termed xenobiotic. Some compounds in this category appear to be non-toxic, some are very toxic, others cause toxicity only at higher exposures or only in compromised individuals. Toxic effects may be acute or chronic . In keeping with the terminology of toxicology, the term toxin will be used to refer to natural substances, toxicant to synthetic chemicals.

However, this document, the third in our series [1,2], is not primarily concerned with toxicology although there will be areas that overlap. Xenobiotic chemicals have been reported to cause adverse effects in a minority of individuals at doses much lower than the lowest sensitivity (MCS) [3-6], that are the main focus of this report. Independent scientists in the USA[7] and the UK[8] have concluded that although there is still much to learn, it can no longer be doubted that MCS is a genuine complaint. There are indications that MCS may be at least partly, allergic in mechanism although not IgE-mediated [9]; the symptoms provoked are similar to those seen in hidden food allergy. The term chemical sensitivity is a term describing the acquisition of a state enhanced sensitivity in which symptoms are provoked by exposures to very low concentrations of chemicals that previously had no effect [4,10]. It does not pre-empt the decision about the mechanism.

Classical toxicology has been concerned with acute and chronic reactions to compounds (not usually examining interactions between chemicals and has sought to establish threshold doses for toxic effects for each chemical below which it has been assumed that the product is without danger to people. However, effects of a range of familiar chemicals on the brain at sub-toxic doses are beginning toto be detected which are obviously likely to cause a rethink [11]. Chronic or delayed effects of exposure are notoriously difficult to detect and attribute, even in experimental animals. This is even more difficult if only a sub-population is involved, or if the effect occurs only with exposures to multiple compounds. Humans are now subjected to a mixture of chemical substances that change , not only from person to person , but also from day to day and from year to year, some of which accumulates in the body. Some evidence suggests that responses to foreign substances entering the body may actually be more damaging than higher levels because they do not trigger the induction of appropriate detoxification enzymes [12]. The full ramifications of the effects of the multiple chemicals to which humans are exposed have not been established but the chronic effects on which this report focuses are in addition to the recognised risks from carcinogenicity and mutagenicity; chemical exposures may also increase susceptibility to other etiological agents, and in particular to the development of allergic disease.

This report will focus on the evidence that adverse reactions occur consistently in a minority of individuals at exposures below the traditionally recognised toxic threshold, and will consider the clinical features and management of such conditions. In some of these cases there is a history of a single toxic exposure but in others the increased susceptibility seems to follow long-term exposure or exposure to multiple chemicals which may all be present at doses below the toxic threshold. The report will examine the extent of the problem, and evidence for the hypothesis that chemical exposures have contributed to the marked increase in the prevalence of allergies and related diseases in the last 200 years, especially the last 50 years .

These are relatively new fields of medical interest. They are neither classical toxicology nor standard allergy, but should be of concern not only to epidemiologists but also to clinicians. In the past , the medical profession has found sporadic cases of MCS difficult to recognise and accept, but this is beginning to change since chemical sensitivity has been recognised in a minority of individuals when groups have been exposed, for instance in work-related exposure incidents [13,14] or in new or refurbished buildings (so called sick building syndrome). Such incidents have been reported in the USA, Canada, the UK and most other countries in Europe.

A major reason for the emphasis on chemical sensitivity in this report is that this important area of human responsiveness has lacked an academic discipline to represent; those concerned with occupational health tend to think only of exposures at work. Physicians who have developed the skills to detect environmental actions among their patients recognise these phenomena on an almost daily basis although, as yet, it has remained largely unacknowledged in the UK. This is likely to change as a result of the independent report commissioned by the UK Health and Safety Executive [8], and by the recent European Union (EU) document [15]. The only previous UK scientific report on this problem, from the campaigning group Friends of the Earth [16], is written solely from the viewpoint of toxicology.

Chemical sensitivity presents regulatory problems to governments and employers with regard to exposure and use, restriction of trade and the provision of safe alternatives. The topic has been considered in a number of symposia and workshops in the USA 17-21].

A comparison of Lactulose Breath Hydrogen Measurements with Gut Fermentation Profiles in Patients with Fungal-type Dysbiosis

J. Nutr. & Env. Med. 2001; 11: 33-42. Eaton, Keith Kenneth, The Princess Margaret Hospital, Osborne Road, Windsor, Berks. SL4 3SJ. Chan,Rebecca. Howard, Mark Andrew. McLaren-Howard, John Michael, Biolab Medical Unit, The Stone House, 9 Weymouth Street, London W1W 6DB. Background. Fungal-type dysbiosis is still an unproven diagnosis. Patients are polysymptomatic, but most have symptoms of irritable bowel. Treatment, using a diet low in fermentable, yeasty and mouldy foods with/or without antifungal drugs, is often rewarding. Patients with the condition also show elevated blood ethanol levels after fasting glucose challenge Because of this a fungal cause has been suggested. These features do not suggest a bacterial overgrowth. Hydrogen generation, on the other hand, is a bacterial fermentation product and would be expected only if a bacterial cause were present. It was therefore decided to compare ethanol and hydrogen production. Methods. Newly referred polysymptomatic untreated adult patients were investigated in a clinic for allergic and environmental diseases. Patients were subjected to two laboratory investigations: a gut fermentation profile which measured ethanol, higher alcohols and short-chain fatty acids, and a lactulose breath hydrogen. These were performed after the initial consultation and reported at the first follow-up visit. Results. Two groups were studied. The first produced excess ethanol (n=18) and the second (n=20) did not. Both groups included patients producing hydrogen. There was no statistical correlation between ethanol and hydrogen production. Conclusions. If fungal-type dysbiosis is solely due to yeasts, our ethanol positive group should not produce hydrogen, but our ethanol negative group should. If the conventional view, that yeasts do not produce hydrogen as a fermentation product, is correct, it appears from the commonness of breath hydrogen positives in this series that bacterial fermentation is in some way implicated in fungal-type dysbiosis.

The Detection of DNA Adducts (Risk Factors for DNA Damage). A Method for Genomic DNA, the Results and Some Effects of Nutritional Intervention

J. Nutr. & Env. Medicine. 2002; 12: 19-31

McLaren Howard, John, Biolab Medical Unit, 9 Weymouth Street, London W1W 6DB, UK


Purpose: Detection of organic chemical and metal DNA adducts in clinical samples.

Design: Open comparison between controls, people having routine laboratory investigations and groups of people with known exposure to toxic chemicals/metals.

Materials and Methods: Using genomic DNA from peripheral blood leucocytes, organic chemical DNA adducts were group separated by gas-liquid chromatography and metal DNA adducts were identified by plasma emission spectrography and spectrophotometry. There were 12 controls, 54 people having routine laboratory investigations, 14 tobacco smokers, seven people with known pesticide exposure, five with known toxic and metal exposure, one person exposed to mycotoxins and two people with known nickel sensitivity. Eight of the participants with positive findings were re-tested after nutritional intervention.

Results: The previous finding of nitrosamine adducts in smokers is confirmed (13 of 14 smokers). Nitrosamine adducts were also found in nine non-smokers. DNA adducts were found to halogenated phenols (10), halogenated benzenes (10), vinyl halides (1), aldehydes (1), chloroethylenes (2), aflatoxin/mycotoxins (5), malondialdehyde (22) and lindane (3). The lindane DNA adduct is a new finding. Seven unidentified adducts were found. Adducts were found to lead (9), cadmium (20), mercury (7), aluminium (1), antimony (4), arsenic (8), nickel (20), strontium (1), copper (1), manganese (4), chromium (1) and cobalt (1). Two of the controls had low-level adducts. In eight people,3 months of nutritional intervention led to the elimination of some DNA adducts and a semi-quantitiative reduction in the level of others.

Conclusions: Significant numbers of DNA adducts can be detected in clinically relevant blood samples. In smokers, the expected nitrosamine adducts are accompanied by cadmium DNA and nickel DNA adducts. Nickel DNA adducts were found in some non-smokers and nickel is a known carcinogen. Lindane DNA adducts are identified for the first time. The results link gene research with the nutritional and environmental approaches to medicine. Early indications are that the burden of DNA adducts may be reduced by nutritional intervention.

Gastric Acid Production, Pancreatic Secretions and Blood Levels of Higher Alcohols in Patients with Fungal-type Dysbiosis of the Gut

J. Nutr. & Env. Medicine. 2002; 12(2): 107-112

Eaton K.K., Gaier H.C., Howard M., McLaren-Howard J and Reid L


Purpose: Patients with gut dysbioses are clinically difficult to distinguish from those with food intolerance. The variety known as fungal-type is associated with the generation of small amounts of ethanol in the blood. A recent study has shown abnormalities of histidine metabolism. In view of this, gastric function was studied. This also provided data on pancreatic function.

Design: Two groups of newly referred patients, with similar symptom profiles, attending two clinicians were studied. Group A (42 patients) had positive ethanol fermentation tests: group B (37 patients) did not. There were 20 healthy control subjects. Levels of higher alcohols, short-chain fatty acids, gastric acid production and pancreatic exocrine secretions were measured and compared statistically.

Materials and Methods: Ehtanol, higher alcohols and short-chain fatty acids were measured by gas-liquid chromatography. Gastric acid production, emptying time and pancreatic function were measured using a swallowed transponder.

Results: A significant number of group A patients had elevated levels of higher alcohols; all of these also showed excess short-chain fatty acids. Group B patients showed similar findings for both; these figures were not statistically significant. However, as compared with group B, group A patients were less likely to show lower levels of gastric acid and/or pancreatic enzyme production and these results were statistically highly significant.

Conclusions: As these findings show minimal effects on stomach and duodenum, it is suggested that fungal-type dysbiosis is largely an ileal condition. For these patients, the presence of elevated levels of higher alcohols with a positive ethanol test is a better indicator of disease severity.

Yeast metabolic products, yeast antigens and yeasts as possible triggers for irritable bowel syndrome

Eur J Gastroenterol Hepatol 2005; 17(1): 21-26

Santelmann, Heiko and Mclaren Howard, John


Many patients with irritable bowel syndrome (IBS) are disillusioned by the lack of efficacy of treatments and suffer from numerous symptoms not covered by the Rome criteria for IBS, as the current empirical treatment regimes fail to address these persistent deliberating 'IBS associated symptoms'. These symptoms are similar to other symptom complexes like chronic fatigue and the so called 'candida syndrome', and many seek help from alternative medicine. The possible role of Candida and yeasts in non-immune compromised individuals is disputed and is the subject of this review.

Even if the involvement of yeasts in the aetiology of IBS still remains unclear, there is increasing evidence for yeasts being able to cause IBS-symptoms in sensitised patients via Candida products, antigens and cross-antigens. But more research is needed before antifungal treatment can be recommended as a first line treatment for IBS.

Muscle Action, Trace Elements and Related Nutrients: The Myothermogram

Howard J

In: Chazot G, Abdulla M, Arnaud P, eds. Current Trends in Trace Element Research: Proceedings of International Symposium on Trace Elements. Paris, 1987, Smith-Gordon, London, 1989, pp79-85


In the investigation of muscle problems it is relatively easy to measure the circulating levels of nutrients known to be involved in muscle function. Such data frequently fail to provide enough information about metabolic problems within the muscle. In diagnosis and in following the treatment of muscle-related problems a functional test is needed.

In the subcellular events responsible for muscle contraction the biochemical energy utilized must equal the energy output of the system and this is essentially the external work done plus the heat energy produced. The external work can be limited so that a plot of the heat produced during contraction and relaxation should reflect the subcellular chemistry. The limiting factors are the difficulty of detecting very small temperature changes and the efficient way in which muscle heat is conducted away by the circulation.

The use of sensitive temperature recording equipment in a clinical test of muscle action is described. Abnormalities of potential diagnostic significance are demonstrated in deficiencies of magnesium, calcium, iron (in children), manganese and folate. The test also detects reduced oxygenation or perfusion and abnormal results are seen in thyroid disorders. It will be shown that muscle damage can result from exercise during magnesium deficiency.

Mineral Deficiencies and Hyperactivity

Howard J

Presented at the Hyperactive Childrens Support Group Conference. Published by HACSG, Chichester, UK, 1987


A brief description of how I first became interested in this subject might help to set the scene. During the nineteen sixties I was involved in some investigations into a possible relationship between exposure to toxic metals and infertility. As part of this work post coital tests were performed. In some types of toxic element accumulation spermatozoa are unable to pass through the cervical mucus due to a problem which is very like that found when anti-sperm antibodies are present. About 50% of the women investigated already had children. During the routine history taking it seemed to me that a rather high proportion of these youngsters were being described as troublesome or problem children.

I was unable to stimulate much interest in this observation among the other doctors and scientists involved with the project. I was, however, given the go ahead for an informal investigation.

As a pilot scale study I chose six of the most troublesome of the children and, with the permission of their parents and their doctors, proceeded to look for possible increases in toxic metals such as lead and cadmium. As my major interest was in the essential elements such as zinc and magnesium I also measured these in the samples from the children. I was actually quite disappointed to find that only one of the children had a high lead and none of them had any other toxic element problems that I could detect. When I looked at the essential element levels a very different situation came to light.

Gut Fermentation (or the "Auto-brewery") Syndrome: A New Clinical Test with Initial Observations and Discussion of Clinical and Biochemical Implications

Hunnisett A, Howard J, Davies S
J. Nutr. Med. 1990;1:33-38


This study demonstrates that alcohol production from oral carbohydrate ingestion is not a rarity but is remarkably common (61%) amongst patients who are chronically unwell. It also presents data to support the use of a new simple clinical test to diagnose gut fermentation that may be due to Candida albicans or other yeasts or bacteria, and thus identify patients who may benefit from a course of anti-yeast or anti-bacterial therapy. (This test does not differentiate between yeast and bacterial fermentation, neither does it exclude large bowel overgrowth of yeasts or "abnormal" bacteria). It is an easy test to perform both technically and clinically, requiring a minimum of laboratory hardware, and it presents to the patient only the discomfort of having two venepunctures (or one for children). It is a test well within the capability of any clinical laboratory and should prove useful in the identification of a cause of a diffuse clinical condition.

Further studies should be carried out, including microbiological culture of gastric and duodenal aspirates in EtOH producers, clinical response to the appropriate anti-yeast or anti-bacterial intervention, and on the stress on dietary micronutrient supply that EtOH production causes.

Magnesium Deficiency in Peripheral Vascular Disease

Howard JMH
J. Nutr. Med. 1990;1:39-49

Background and Introduction

Many studies have shown that magnesium deficiency is an important factor in the aetiology of cariovascular disease. In 1965, the relationship between myocardial infarction and low Mg levels was investigated in terms of platelet aggregation. In 1977, it was concluded that Mg plays an important role in cardiac homeostatis and that cardiac diseases are associated with Mg deficiency. Electrocardiographic changes characteristic of Mg deficiency were reported. The biochemical aspects were further investigated.

Serum, Leucocyte, Sweat and Hair Zinc Levels a Correlational Study

Howard JMH
J. Nutr. Med. 1990;1:119-126


Doctors investigating the zinc status of their patients must not rely on serum zinc levels which will only identify quite severe deficiencies. Low hair zinc levels do reflect deficiencies, but a normal or high level of zinc in the hair cannot exclude a deficiency due to the affect on hair growth rate. High hair zinc should alert one to the possibility of a zinc deficiency, but there are many shampoos and other cosmetic treatments that contain zinc. A high hair zinc may also reflect other causes of poor hair growth rate such as hypothyroidism or zinc or iron deficiency.

Both sweat zinc and leucocyte zinc levels are good tests of zinc status, with sweat the sample of choice in this study. If the different populations of white cells are separated and analysed independently, my initial studies suggest that white cell zinc may be as good as sweat zinc in assessing zinc status. The collection of sweat samples and the harvesting of uncontaminated white cell fractions from blood samples are both time-consuming and difficult procedures. Deciding which of these techniques to use in a particular clinical laboratory may depend on which technique the staff are most conversant with. I would encourage those laboratories with the necessary analytical equipment to pursue the use of sweat zinc measurements. If they are also willing to measure leucocyte zinc, then the combination of the two techniques will provide a very high level of service for the assessment of zinc status.

One advantage of the sweat test procedure is that it is non-invasive and hence very suitable for use with children or nervous patients.

I hope that the comparison of results for hair, serum, leucocyte and sweat zinc levels will be helpful to those considering a diagnosis of zinc deficiency. Laboratories are under increasing pressure to assess zinc status, and this work may help those responsible for introducing the techniques to avoid some of the pitfalls when the wrong choice of sample is made.

Finally, I wish to emphasise the danger of relying on the serum zinc levels as an indicator of zinc status.

T. C. Chamberlin and The method of method of multiple working hypotheses': Its relevance to clinical medicine today, 100 years after publication

Stephen Davies
J.Nutr. & Env. Med. 1997; 4: 233-235

This paper celebrates the centenary of the publication of a milestone paper written by geologist T. C. Chamberlin and highlights how the intellectual process of the method of multiple working hypotheses is a more effective and less problematic way of arriving at the truth of a given situation. This approach has as much relevance today as it did a hundred years ago. It is proposed that the current pharmacodox paradigm might, in fact, be an example of the less intellectually developed method of the ruling theory.