Home

Doctors

Patients

Tests

News

Publications

Index

Contact us

CURRENT NEWS AND BIOLAB TESTS September 2003

Introduction

Continuing the occasional series of brief comments from Dr John McLaren Howard, Laboratory Director, on medical and general news items together with Biolab tests that may be useful in the investigation of these areas of concern. Your feedback on the questions posed below will help us in developing future individual tests and test profiles.

 Ritalin and hyperactivity (ADHD)

Almost a quarter of a million prescriptions for Ritalin were issued in 2002! As far as I can determine, official figures suggest that 306 youngsters had serious side effects. There was one death earlier this year and three others died in 1997, 1998, and 2001. Biolab has enjoyed a long relationship with the Hyperactive Childrens Support Group whose excellent work has helped so many parents. They, and we, promote a non-drug approach to ADHD. There is certainly enough evidence to suggest that the use of Ritalin should be the last resort. Tests that can be helpful include general nutritional screening, the Gastrogram (assessing gastric acid and pancreatic enzyme function), urinary Kryptoppyroles (increased in concurrent zinc and B6 deficiencies) and essential fatty acids (delta-6-desaturase block is very common in ADHD). Some of the children also have increased levels of toxic metals and many have allergic problems that include gluten sensitivity. Measuring antigliadin antibodies can negate the need for Jejunal Biopsy.

 Autism – some new findings

In addition to dealing with specific test requests in Autism, we have performed a range of tests on 61 Autistic children where tests additional to those initially requested have been performed without charge but with the full consent of parents and the referring doctor. We have seen an unexpectedly high incidence of abnormal levels of Short-Chain Polypeptides (usually from incomplete digestion of protein) and DNA-adducts to toxic metals. Polypeptides can mimic hormones (especially gut hormones) and cytokines (immune-system-messenger-chemicals).

 Vitamin C

Among many important functions, vitamin C is required for the formation of collagen. In this process, vitamin C hydroxylates proline and lysine inside cells. These help to form the pre-cursor, pro-collagen that is later used to promote the formation of collagen outside of the cells. As well as its obvious implications for bone formation, collagen is critical to the integrity of blood vessels, arterial compliance and it is an essential factor in wound healing. Of course, vitamin C is also important as an antioxidant, for the absorption of iron and in correct immune function. In some cases, the measurement of vitamin C can be useful in determining whether a low level is likely to be playing a causative part in the patient’s illness. When vitamin C supplements are already in use, the best test is leucocyte vitamin C. For those not taking supplemental vitamin C, the cheaper serum  vitamin C level is adequate.

 Carbamates as endocrine disrupters and sensitising chemicals

Carbamates are very effective pesticides that are used World-wide. Agricultural run-off can contaminate water sources and might end up in drinking water. Direct exposure to carbamates is not a major factor for most of the general population but concerns about trace levels of these compounds has increased. The water industry is increasingly challenged to provide assurances that supplies are safe with regard to these endocrine-disrupting chemicals. The analytical methods available have been insufficiently sensitive for the detection of trace amounts. New developments in a combination of liquid chromatography and mass spectrometry (LC/MS) have moved a long way towards a highly sensitive environmental screen for 46 of the 52 carbamates targeted.

 The Biolab pesticides screen does look for a number of carbamates in blood and fat samples. Recent analytical improvements have increased the sensitivity of our test and we continue to research this area. It is the endocrine disrupting capacity of low levels of carbamates that is triggering increased awareness but I have an additional concern about these chemicals. In some people, they seem to be a factor in the development of chemical sensitivity. This is most apparent in those exposed to Carbaryl who often become sensitive to alpha-naphthol. This chemical is the major metabolite of the pesticide and it is also used in the preparation of dyes.

 Endocrine disrupting chemicals in general

Much of the concern about endocrine disrupting chemicals has centred on the effects of environmental oestrogens on male reproduction. A wide range of chemicals have oestrogenic properties but exposure level is not of itself a reliable predictor of unwanted affects on human metabolism. The individual’s endogenous hormone balance, their nutrient status and any underlying disease conditions can influence both the up-take and the effect of exposure. Equally, chemicals that predispose to conditions such as testicular and breast cancer can, in some people, be present at increased levels without promoting a malignancy while low level exposure is associated with neoplasm in others.

 The chemicals that have been investigated as hormone disrupters and/or promoters on hormonally sensitive tissue malignancies now covers a disturbingly wide range. As a ‘detective’ laboratory, we are asked to assess individual patient exposure to these chemicals and deliver results that are meaningful in terms of risk factors as well as possible causative factors in those who are already ill. This is a tall order!

 However, it is an area of increasing concern and it does connect with two specialised investigations that we already do. We look for and semi-quantify DNA adducts and we measure short-chain polypeptides in blood serum. DNA adducts are chemical addition compounds with DNA that can disturb the way the DNA code is read. The metabolic consequences depend on the location of the adduct on the DNA. In addition to disruption of specific enzyme/protein synthesis, adducts can activate oncogenes or block anti-tumour genes.

 Increases in circulating short-chain polypeptides (SCPP) can result from inadequate protein digestion and/or increased gut permeability. When present, they can mimic hormones and cytokines thereby disrupting endocrine or immune function. In some patients, a further source of SCPPs is inappropriate production of a small molecule hormone (or hormone look-alike) from tissues affected by chemical exposure. This can lead to a further amplification of the endocrine disrupting effect of the chemical.

 Your comments please? It would be very expensive to test for all the known endocrine disrupters but I am concerned that we currently only address this difficult area in a piece-meal way. I would like your help in deciding whether to invest the considerable time and energy that would be required to develop a profile of appropriate tests. A way of lowering the cost of this screening would be to do what we do with the DNA adducts where we identify organic chemical adducts by their chemical grouping rather than as individual compounds. If applied to a more general screen of environmental chemicals, we could include DNA adducts and SCPPs in the proposed profile. I do not yet have any way of assessing overall oestrogenic effects but that is under investigation here and elsewhere.

 Please let me know if the availability of such a profile would be of use to you in your clinical practice?

 Osteoporosis

It is now estimated that one in three women and one in 12 men are affected by some degree of bone loss. How clinically relevant this is will depend on their peak bone density or bone mass earlier in life and whether the bone loss is rapid enough to present a major risk within their probable life span.

We presently offer an osteoporosis screen that looks at the balance between bone alkaline phosphatase (bone production) and tartrate-resistant acid phosphatase (bone resorption). The profile includes studies of the status of nutrients that are known to be involved in bone metabolism and the urinary excretion products that increase during bone loss.

Should we expand this profile by including other markers of bone metabolism? Do you have a favourite test that you would like to see in this profile? If so, please let me know what it is and its usefulness in your own experience.

Giving up smoking

We can all sympathise with those who genuinely find it hard to stop smoking. For some of them the loss of the psychological prop is too much to cope with while for others the physical addiction is the limiting factor. Recent work has shown that a mutant gene (known as CYP2A6del) is a defective variant of a gene that promotes the induction of enzymes that help to break down nicotine. People with this defect have much more difficulty when they try to stop smoking.

In our work on DNA adducts we have confirmed what other workers have found that smokers frequently have adducts to nitrosamines. We have also identified cadmium and nickel adducts in at least 50% of smokers. We are not able to determine whether these adducts block the gene referred to above or promote a mutation of it but that is a possibility. What we are seeing is that the smokers with these toxic metals adducts have the greatest struggle when they try to give up.

As nutrient intervention seems to be able to reduce the adduct burden, it can be valuable to identify these patients in order to facilitate their efforts to break the habit. Reducing the adduct burden should also reduce the cancer risk.

Zinc supplement levels

High-level zinc supplementation can impair immune function. This is not a new finding but it is confirmed by studies that show that excessive zinc supplementation can increase the risk of prostate cancer. The study involved 50,000 American males and covered a 14 year period.

Biolab is not able to undertake such large studies but we have seen six patients where immune function has been compromised by high dose zinc supplements either self-prescribed (2 cases), prescribed by their doctor (3 cases) or by a nutritionist (1 case). The doses ranged from 60 to a massive 400mg of zinc each day.

We have never seen this effect in any patient taking less than 60mg each day. We would never suggest a zinc dose that exceeds 50mg per day and it is my own feeling that any patient whose zinc status does not replete on 30mg per day is taking the wrong form of supplement, taking it with food or has a severe malabsorption. Zinc, copper and iron compete with one another in the gut. Zinc supplements should be taken on an empty stomach either last thing at night or half-way between meals.

Supplemental zinc citrate gives a very high serum zinc peak but much of the zinc is rapidly lost in the urine. For most patients, zinc as a simple amino acid chelate (zinc gluconate is inexpensive) works well and gives an increased serum level for up to four hours after ingestion.

Please note that zinc orotate is poorly absorbed and not absorbed at all by around 25 to 30% of people. It should not be used.

DVT, travel and obesity

There is no doubt that sitting for long periods without exercising the legs increases the risk of DVT. Obesity is also a factor in some cases. The airlines have experienced a very bad press over this issue, perhaps, not too unfairly given the cramped seating provided in some aircraft. However, they are now giving advice to passengers and it seems logical that simple exercises and getting up to walk around will be helpful.

Simple nutritional measures may also be of value. Vitamin E and omega-3 fatty acids are particularly helpful in the avoidance of venous thrombosis. However, these cannot be expected to fully protect people who adopt positions that restrict venous return. As advisers and as travellers ourselves, we all need to promote active measures to avoid venous congestion.

We should also encourage those who suffer from cramped conditions in flight, or for that matter in road or rail travel, to complain to the operating company. Airlines, in particular, are likely to find that laws are passed to define passenger space and seating conditions unless they take this matter seriously and act rapidly. DVT is a potentially very serious condition but it is one where simple forethought and inexpensive measures can reduce its incidence in a highly significant way.

Disease-related test profiles

Dr Alan Stewart recently drew our attention to the need for disease-related profiles. This is not the first time that we have considered this possibility but, with the exception of the osteoporosis profile, we have done little about it and the reminder is timely.

Dr Stewart has made suggestions for profiles for appropriate nutritional investigations.  As he points out, it is helpful if we distinguish between main-stream tests that are well documented and understood by many doctors and those that are more specialist areas that may still be the subject of ongoing research.

I think the best way of making this distinction would be by offering a basic profile with the option of widening this to include some of the newer tests. A list is appended to this Newsletter. The basic profiles are based on Dr Stewart’s recommendations and the extended profiles include other tests that I consider appropriate when a wider investigation is justified.

These profiles can be requested by writing their title in the ‘Other Tests’ space on the request form. However, if you want a different spectrum of tests we need you to tick the individual test boxes.

We hope it will help to have these profiles available. We are all familiar with the feeling of not being clear about the nutritional test requirements when we see a patient with a proven disease that we infrequently see. These profiles may also be helpful to doctors who rarely use the laboratory or whose knowledge of the nutritional factors in a specific disease is limited.

Disease related profiles

Return to news page


If you require further details about these news items or or any further information about Biolab please contact us directly: info@biolab.co.uk