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

16 responses to “How Relevant Are Holford’s Claims About Homocysteine Levels? Part 1

  1. ach

    [quote]Homocysteine is a naturally-occurring protein that’s found in the blood.[/quote]

    No, it isn’t. It’s a homologue of cysteine, which is an amino acid. If Holford doesn’t know the difference between an amino acid and a protein, I hardly think he’s likely to grasp the finer points of the epidemiology of CHD.

  2. Shinga

    Point taken – there gets to be a point where it feels quite mean to be picking at every detail because it means there is a problem with the majority of that article. However, it wasn’t finer points of epidemiology that he misquoted, he managed to misquote the very straightforward material that required no interpretation.

    The next couple of parts are going to address his claims about the role of homocysteine levels in predicting the need for restenois (part of his platform for justifying Hcy testing) and then the trials that look at the predictive role of Hcy in a healthy population.

  3. James

    Do you think he has a link to any private testing companies who offer Hcy testing. It does seem that his enthusiasm for these tests is swiftly followed by an offer on his website (e.g. IgG testing for ‘allergies’)

  4. Shinga

    Golly James – do you have a crystal ball or something? Yes, Holford’s Health Products for Life recommends the YorkTest Homocysteine test at £75 per pop, 2-3 times a year to baseline and tweak your levels with supplements (£41.60 for 30-90 days, depending on the dosage).

  5. coracle

    Great work Shinga, nice to see the issue dealt with so thoroughly.

  6. Shinga

    Thank you, Coracle. I do occasionally feel that I should just set aspects of this article as a summer task for students. E.g., one could have followed up on the historical claims; another the restenosis studies; still another could examine the magnesium claims; one might have taken a critical look at the supplementation recommendations; another might have reported on the acknowledged difficulties in standardising plasma total Hcy tests between laboratories etc. And this is only one article (albeit, it seems to be the summary of the book).

    It will be interesting to see whether the publishers ask for revisions to the text (in the event of a re-issue) or if they will need to print extensive errata slips.

    Regards – Shinga

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  11. fiona

    My SIL’s doctor has been trying to talk her into these tests although they are off insurance. I suspected that they would be no more than a gateway into more tests and non-insurance covered supplements.

    Thanks for the information.

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  13. Martin Semple

    I suggest people with a responsible interest in this (rather than just smart-assing subjectively against a favourite scapegoat) might usefully look at the thorough article on Homocysteine by Stephen Barrett, M.D. on the quackwatch website. Why not go to the relevant primary source studies yourselves. And while you’re about it, take a close look at studies on the relationship between Homocysteine levels and Alzheimer risks.

    No, I’m not a Holford trained nutritionist. I have absolutely no vested interest; but I’ve followed his career with interest for twenty years – yes he talks in high-contrast, broad-brush, terms. But through his 30+ books, his consistent gathering of current research, and his ability to popularize the findings, he has – as a matter of fact – helped many thousands to a far more sensible approach to their own health than have any of his detractors. Before knee-jerking in response to this posting, ask yourself “How many people have YOU helped?”

    Why don’t you use this site to simply publish all the relevant sources and leave out all these tedious attacks.


    • Why not go to the relevant primary source studies yourselves. And while you’re about it, take a close look at studies on the relationship between Homocysteine levels and Alzheimer risks.

      Fair point, Martin. We do avoid reading research articles on this site [/sarcasm]

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  15. Avinde

    I have no doubt that Patrick Holford will be proved right on many issues.

    Don’t forget that it was those nutty naturopaths a century ago who first suggested that smoking was harmful.

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