Category Archives: hometesting

Homocysteine, B Vitamins, Brain Atrophy and Mild Cognitive Impairment

A new PLoS article has been published, arguing that

The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins

I don’t have time to deal with this in as much detail as I would like (lots of things getting in the way of blogging, which is why it has been quiet here lately) but I think this is worth some quick notes. This post is short and a bit messy: for a summary of what the article does and doesn’t know, see Behind the Headlines; for a summary of some concerns with it, see Evidence Matters. Keep reading if you’re interested in the Holford angle. Continue reading

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Filed under hometesting, homocysteine, yorktest

Patrick Holford Claims More People Die, Prematurely, From Cardiovascular Disease Than Actually Die, Prematurely, From All Causes

Patrick Holford on ITV Lunchtime 16 April 2008
Former Visiting Professor Patrick Holford is Head of Science and Education at Biocare. Despite the imprimatur of respectability about these confidence-inspiring titles, from time to time, there are disappointing errors in the content of Holford’s health advice and sales pitches for home tests and the evidence base for supplements. These errors are all the more dispiriting when one recalls that he was corrected about some of them more than two years ago. We don’t mean differences of opinion, we mean verifiable, checkable facts. When Holford persuades people to rely upon his opinion and lend credence to it because he undertakes to do the scientific research and interpret it for them then it seems inappropriate to claim that more people died, prematurely, from a specific cause than actually died, prematurely, from all causes. Continue reading


Filed under Holford, home test, hometesting, homocysteine, patrick holford, supplements

Patrick Holford Still Advocates IgG Testing for Food Allergies

Professor Patrick Holford of Teesside University and Head of Science and Education at Biocare frequently upbraids professionals and researchers for what he perceives as their lack of up-to-date research.

Holford’s 100%health newsletter for November 2007 is full of the usual inexactitudes and creative interpretations of quite straightforward research. He once again conflates allergies and intolerance and discusses IgG as if it is relevant to any such discussion. Continue reading


Filed under allergies, allergy, ASA, food intolerance, food sensitivity, Holford, home test, hometesting, IgG tests, lactose intolerance, patrick holford, Scadding, supplements, yorktest

How Relevant Are Holford’s Claims About Homocysteine Levels? Part 1

Patrick Holford and Dr. James Braly wrote a book about homocysteine and assert that it is “the best single indicator of whether you are likely to live long or die young: The H-Factor Solution. According to Holford and Braly, homocysteine is:

[l]ike a chemical crystal ball, it reveals exactly what we should be doing to guarantee our future health…your H score predicts your risk of more than 100 diseases and medical conditions-including increased risk of premature death from all common causes.

Holford and Braly’s claims for the value of homocysteine are extraordinary. However, the proof that Holford offers is less impressive; particularly against the background of an article about homocysteine and coronary vascular disease (CVD) in which he substantially overstates the risk of premature death from CVD.

You might expect that any claims would be based on a balanced overview of all the research literature about homocysteine: any causal links to clinical conditions; its predictive value; whether it is possible to lower homocysteine levels with a therapeutic intervention; whether lowering homocysteine levels reduces the risk of disease, or poor outcomes in disease. I can’t comment on the book, but Holford does not do this in relevant articles on his website.

Holford is enthusiastic about the homocysteine test. The test is a significant part of his claims that you can follow his advice and learn How to Eliminate Your Risk of Ever Having a Heart Attack. I should emphasise that your homocysteine level is not a diagnostic test: it is not something like a cardiac enzyme study that can determine whether you’ve recently had a heart attack. If it’s not diagnostic, is it predictive? Does this test tell you something about your risk profile that is more meaningful than other sources of information such as a physical examination alongside a detailed family history? According to Holford:

[t]he single greatest risk of a heart attack comes from having a high homocysteine level. Homocysteine is a naturally-occurring protein that’s found in the blood. If you’ve had a heart attack, the chances that you have an unacceptably high homocysteine score (over 9 units) are well above 50 per cent. About 30 per cent of you will have a level above 15 units, which is very high. Very conservatively, I estimate that at least 8 million people in Britain have dangerously high homocysteine, increasing their risk of a heart attack by at least 50 per cent.

I’m going to go out on a limb and say that your “single greatest risk of a heart attack” is whether or not you’ve already had a heart attack, followed by your age (67% of deaths from CHD occur in those aged 75 and above figures calculated from British Heart Foundation statistics report (pdf)). I’m also going to say that there are some conditions, such as familial hyperlipidaemia that would raise a red flag and should be fully investigated before considering the need for a homocysteine test.

Gene Sherpa, Dr. Steve Murphy, provides fascinating insights into the role of genetics in personalised medicine. He emphasises the research that shows time and again that a good family clinical history is the best and cheapest genetic risk assessment that trumps most offerings from a direct-to-consumer testing service. He has recently commented on the importance of family history when estimating the risk of stroke. Murphy outlines research into a genetic variation that might affect homocysteine/folate/one carbon metabolism and raises questions about whether vitamin status plays a role. This might look like a showcase example of the need for nutrigenomics: how the appropriate diet and supplements can reduce risks attributable to individual variation. However, Murphy cautions that all is not as it seems:

  1. Homocysteine is only poorly linked to heart disease in asymptomatic patients
  2. There is some literature which states that B vitamin supplementation in patients with prior heart attack can cause WORSE outcomes.
  3. This is a replicated study, but not on a heterogeneous population………..

Basing his advice on the current state of knowledge, Murphy counsels that people who have already had a heart attack should not supplement B vitamins.

The following are some of the causes or proposed correlates of elevated homocysteine levels:

  1. defect in the transsulfuration pathway / deficiency in cystathionine B-synthase
  2. defect in the remethylation pathway / defective methylcobalamin synthesis or abnormality in MTHFR
  3. Proposed sources of abnormalities
    1. genetic predisposition

    2. genetic predisposition exacerbated by co-morbid conditions and/or nutritional and environmental factors:
      1. abnormal MTHFR
      2. chronic renal failure
      3. hypothyroidism
      4. methotrexate therapy
      5. oral contraceptive use
      6. malignancies of breast, ovary, and psoriasis
      7. smoking
      8. high alcohol consumption
      9. age

For most of these, you would need a skilled interpretation of your homocysteine levels alongside your clinical history: it might be very unwise to self-medicate to adjust homocysteine levels without allowing for relevant clinical details.

If the question about homocysteine measurement is, “For the general population, does this test tell you something about your risk profile for heart attacks that is more meaningful than other sources of information such as a physical examination alongside a detailed medical and family history?”, the answer would seem to be “No”. Holford and Braly may well have been right when they likened homocysteine to a “chemical crystal ball”; it is a matter of judgment for readers to decide whether or not they consider a “crystal ball” to be a reliable source of information.


Filed under hometesting, homocysteine, james braly, patrick holford, vitamins

Running out of tolerance: allergy, intolerance and Coeliac Disease

In an Independent article, Holford appears to confuse wheat allergy and gluten intolerance. On March 30, his 100% Health e-mail newsletter asked “Could gluten be undermining your health?” However he seems, again, to have conflated allergy and intolerance.

Holford begins the e-mail by saying that “Gluten allergy – or coeliac disease – used to be considered a rare condition, but new research suggests that 1 in 100 may be affected”.

The Food Standards Agency (FSA) has a nice clear account of the difference between food allergy and intolerance:

Food allergy and food intolerance are both types of food sensitivity. When someone has a food allergy, their immune system reacts to a particular food as if it isn’t safe. If someone has a severe food allergy, this can cause a life-threatening reaction.

Holford usually claims some significance (not supported by expert opinion) for IgG levels as diagnostic of food intolerance; however, one thing on which most people agree is that this sort of food intolerance doesn’t involve the IgE immune system and is generally not life-threatening. But if someone eats a food they are intolerant to, this could make them feel ill or affect their long-term health.

Coeliac disease can be wretchedly debilitating – the symptoms from this can be horrible. However, unlike an IgE-mediated allergic reaction, diagnosed and managed coeliac disease is unlikely to cause a sudden-onset of life-threatening problems. Coeliac Disease provokes a non-IgE mediated reaction brought about in genetically susceptible individuals by exposure to the gluten in wheat and other cereal grains; it functions through a different mechanism to an IgE wheat allergy. It’s therefore important to distinguish between the usual sort of wheat allergy and intolerance that Holford usually conflates and Coeliac Disease – but Holford often fails to do this.

The FSA is right to say that “[i]f you think you have a food allergy or intolerance, then it’s important to get a proper diagnosis.” However, in the 100% Health e-mail Holford suggests hometesting for IgAtTG – by a wonderful coincidence, Holford’s Health Products for Life sells such tests.

Looking on pubmed, IgAtTG was formerly recommended for checking that coeliac patients have been sticking to their gluten-free diet. More recently, Biocard has been promoted as a form of rapid-testing for Coeliac Disease; however, although these tests have been validated, and are comparatively easy for an expert to interpret, it is not necessarily straightforward for the general consumer (see also, Update 2). It is possible for a test to have very high specificity and sensitivity when used by appropriately trained and experienced personnel but to have very different accuracy when used by the general consumer who is (presumably) seeing and using the test for the first time.

However, Holford markets this test as reliable for home use and tacks between discussions of wheat allergy, intolerance and Coeliac Disease, conflating IgG and IgE mechanisms and sometimes equating this conditions. It is vitally important to distinguish these because they have very different implications for quality of life; [update, April] as pointed out in our comments, people with Coeliac Disease qualify for financial support and prescriptions to defray the costs of what would otherwise be very expensive diet. They also qualify for expert guidance from dietitians.

The only article Holford mentions* as support for his marketing is an article I haven’t been able to find in pubmed, or in the referenced journal’s table of contents.

Holford also notes that testing for IgAtTG will ‘diagnose’ celiac disease in a surprising number of people:

[t]he old view was that about 1 in 5,000 people had coeliac disease, the genetically transferred digestive and malnutrition disorder caused by an extreme allergy to gluten. However, new research shows that gluten allergy affects possibly as many as 1 in 100 normal, symptom-free people, often showing no digestive symptoms at all

This is an on-going debate among researchers who have dedicated their work to this topic. If a new, relatively unvalidated as a direct-to-consumer test ‘diagnoses’ a disease in apparently healthy people, the first ‘obvious’ question is whether the test is generating false positives. A second obvious question is – if the ‘disease’ isn’t causing any ill health – whether there’s any reason to modify one’s diet (there may be) and if there are any consequences to transforming someone into a potentially ill person. As explained on the wonderful BreathSpa blog, even if a reliable test shows “sensitisation” to a substance, if this is not causing any problems then this sensitisation may “not [be] clinical disease”, and it might be inappropriate to treat it as such. The consultant allergist Dr Scadding goes on to argue that:

you can not have self-testing kits: they’re going to lead to mis-diagnosis, mis-allergen avoidance. You need both the test and a detailed history taken by somebody who has some experience of allergy history taking and interpretation of tests.

To summarise, then, Holford makes the dangerous mistake of conflating wheat allergy and gluten intolerance. He also advocates – and sells – what he calls “gluten allergy” testing kits. Holford is promoting these these kits as diagnostic of Coedliac disease and what he styles as gluten intolerance; however, looking at the peer-reviewed medical literature, I can’t find convincing evidence that they actually work for intolerance in the sense that Holford typically uses this term. The final nail in this proverbial coffin is that – even if these tests did work (and they are part of the portfolio for managing Coeliac Disease) – it’s unlikely that home testing would be appropriate. For Coeliac Disease, you need a qualified gastroenterologist or similar to take a case history, and to interpret whether or not the presence of IgAtTG antibodies in the blood does show the presence of a clinical condition (which requires treatment with gluten-free diet etc.). Following such tests, you may need to confirm the diagnosis with an endoscopy and/or biopsy.

Neither Coeliac disease, nor wheat allergy, are trivial matters. They need to be diagnosed and treated properly, not using an home test that may be inappropriate for direct-to-consumer use – sold by a nutritional ‘expert’ who fails even to distinguish wheat allergies and intolerances or Coeliac Disease.

Update 4 Jan 2008: Coeliac UK expresses caution about these home tests.

While we welcome a new tool that could help to get more people diagnosed we would stress that blood tests for coeliac disease are not 100% accurate and there are individuals who may have false negative results – even if they have not changed their diet. The self-testing kits should not replace a medical diagnosis and we recommend that if anyone has symptoms of coeliac disease they should go to their GP. [Coeliac UK goes into more detail (pdf).]

Update 2 16 Jan: There may be a role for such rapid test facilities for Coeliac Disease when used by a GP or Practice Nurse (Medscape; free on registration). However, a recent study of population screening for Coeliac Disease among 6-year-olds is a useful illustration that the specificity and sensitivity of a test may change, depending on who is interpreting the results. E.g., in this study District Nurses (the majority of whom had received some basic level of training) performed the rapid testing with the same test that Holford promotes, and yielded a disappointing 78.1% sensitivity but excellent specificity of 100%.

The rapid test seemed to be as accurate as laboratory testing and had a high positive predictive value and specificity. Some training is needed, however, to enable faint test lines to be recognised when circulating antibody concentrations are low. As with all visual tests, observer variability can affect the results, so the diagnosis should always be verified by histology.

It is for these reasons that Holford Watch questions whether it is truly ’empowering’ for consumers to be persuaded to pay for a test that they may not be able to interpret correctly and would need further validation from a GP.

There is an interesting discussion to be had about the cost-benefit to the individual and society of mass-screening for Coeliac Disease. There is undoubtedly a need for more education and awareness of Coeliac Disease; however, this discussion is hampered when self-styled experts confuse the matter for the general public by conflating Coeliac Disease with IgE food allergies or so-called IgG food allergy/intolerance.


*Gerarduzzi T et al. Celiac disease in USA among risk groups and general population in USA. Journal of Pediatric Gastroenterology and Nutrition. Vol 31 (suppl) 2000: pp S29, Abst 104. [Having searched Jnl of Ped Gastro and Nutr, this paper doesn’t seem to exist as per this reference. It appears in Google Scholar as a citation only which might indicate an error.]


Filed under allergies, Coeliac Disease, gluten intolerance, hometesting, intolerance, patrick holford, wheat allergy