Tag Archives: homocysteine

Oxford University, Food for the Brain, Alzheimer’s Disease and a Curious Test

The People’s Medical Journal (aka Daily Mail) has a touching faith in the value of early diagnosis and screening tests. It would be rather charming to note that their history of being wrong has not as yet reduced them to cynicism if it were not for the errors and false hope that they present as verified fact to their readers.

Food for the Brain (CEO Patrick Holford) claims to offer an online test to detect the early symptoms of Alzheimer’s Disease. Alzheimer’s Disease is a subject that excites great concern and, by definition, those who research in this area are aware that they are typically dealing with some vulnerable people.

Dr Margaret McCartney recently examined the claims for Food for the Brain and self administered cognitive tests after some enthusiastic media reports and found them unwarranted, and not in line with available evidence. She evaluated the claims again in the BMJ, An early warning for Alzheimer’s disease, and questioned FFTB about the claims made for the test in the diagnosis of Alzheimer’s Disease or its prodromes and the evidence base for its recommendations.

Patrick Holford, who describes himself as a “nutritionist” and chief executive officer of Food for the Brain, told me, “We, the charity, deemed the evidence to have become substantial enough to warrant the launch of our Alzheimer’s prevention project . . . the primary aim of which is to encourage early screening of cognitive function from age 50, followed by homocysteine testing.” Food for the Brain’s adviser, the pharmacologist David Smith, told me that the online test is “not a diagnostic test, and there is no definitive outcome; it simply tells the user about their cognitive status.

So, media coverage (eg, 15-minute online test for dementia: DIY memory quiz detects early signs of Alzheimer’s in people as young as 50; Online test for early signs of Alzheimer’s) persuaded people to take an online Cognitive Function Test (CFT) developed by an “Oxford research team” as a way of detecting the early symptoms of Alzheimer’s Disease and as a way of persuading them to take/pay for non-evidence-based tests and supplements. However, Professor David Smith, Chairman of FFTB’s Scientific Advisory Board, admits that the test has no diagnostic value. (Holfordwatch readers with a good memory will recall that David Smith has previously admitted that FFTB has not done a “proper job” of research it attempted.)

As is too frequently the case when discussing Patrick Holford and Food for the Brain, it is difficult to outline all of the misunderstandings and errors that accompany their claims. We can’t begin to cover all of the issues which, inevitably, also involve: the inappropriate promotion of the crystal-ball of homocysteine testing as a biomarker; the advice that test takers should ask their GPs for a test that is not available for that purpose on the NHS or have recourse to Yorktest private testing; the promotion of supplements. This is not the time to explore the ethical concerns that must accompany the availability of a direct to consumer test that purports to diagnose such a widely-feared condition and has already caused some distress while also illustrating a worrying (and perhaps unwarranted) confidence in the significance/value of the test.[1]

The following is not a complete account as the story is still unfolding, however, even these items highlight the contested nature of this test and why the marketing/media coverage of it is inappropriate. The inconsistencies and recent redactions must also question whether the test ought still be available until such time as various issues are clarified. It isn’t clear why Oxford is failing to protect its reputation as it can not be to its advantage to be associated with such a questionable test and set of recommendations.

i) Mid-May various media outlets covered FFTB’s Cognitive Function Test (CFT): they reported that it had been developed by an “Oxford research team” and was made available online, direct to consumers, and promoted as diagnostic of Alzheimer’s Disease and its prodromes.

Food for the Brain (FFTB) emphasised the involvement of Oxford University in news stories and the then current version of its own website: Patrick Holford has likewise stressed the involvement of Oxford Uni. in his marketing materials for his own website and for FFTB for which he is the CEO. Oxford researchers are said to have played the role of lead developer.[2]

However, approaches to several people, including Virginia’s Professor Timothy Salthouse and Oxford’s Dr Celeste de Jager, subsequently revealed that neither of them played such a substantial role in the development of the test.

Professor Salthouse reports that he granted permission to the authors to use an adapted version of his perceptual comparison tests. However, he emphasises that that is the extent of his involvement and makes no claims with respect to the role of his tests in assessing the risk of memory decline or the development of Alzheimer’s Disease.

Dr de Jager’s involvement was recently clarified by an amendment to the FFTB website:

The CFT composes three elements:
A Episodic memory, using cued recall and paired associate learning test constructs, developed by Catharine Trustram Eve for FFB, with the advice of Dr Celeste de Jager.

So, it seems as if the test, developed by an “Oxford research team”, was substantially the work of Catharine Trustram Eve who is listed as an “Independent Market Research Professional” albeit that is not made clear in the Letter to GPs that test-takers are advised to give their doctors. Catharine Trustram Eve’s profile does not list any qualifications in neurology, psychology, cognitive science or similar relevant disciplines.

How many test-takers took the test because they were reassured by the much publicised Oxford provenance of the CFT? What, if anything, is Oxford doing to dissociate itself from the CFT? Even today, the Daily Mail is linking Oxford and this test: Test to detect early onset of Alzheimer’s for all over 65s to be introduced within two years.

One of the items in the box insert states:

“Oxford University has devised a memory test that can be taken at home in 15 minutes and can spot the signs of Alzheimer’s in people as young as 50.”

Both Patrick Holford and Food for the Brain promoted the CFT to their mailing lists. Why have neither Patrick Holford nor Food for the Brain issued corrections to their mailing lists to clarify the provenance of the test?

ii) The CFT is said to be validated for a specific age range and it is promoted as diagnostic in news coverage and on the FFTB website.[2], [3] However, as Dr McCartney explains, at the time of the news items, the validation for this test was not available and there were no data relating to sensitivity or specificity (false positives and false negatives).

The Daily Mail story (inter alia) refers to pilot studies:

The researchers cannot put a figure on the test’s accuracy, but in pilot studies it worked as well as tests already used in GP surgeries and specialist memory clinics.

In the absence of detail that would allow for appropriate scrutiny, the claims for validation were premature at best. Irritatingly, in late May the FFTB site was amended to state:

“based on the pilot, it appears that the CFT is sensitive to MCI. A full description of the pilot and analysis will be available from this page by 1st July 2011.”

http://www.foodforthebrain.org/content.asp?id_Content=1825

However, following the latest updates to the FFTB website, we now learn that we are not to be permitted to see the detail that ‘validates’ these tests for some time:

“Previously it was stated that ‘A full description of the pilot and analysis will be available from this page by 1st July 2011.’ However, in light of an expert academic critique of the CFT validation, we have decided to submit the work for publication prior to publicising the results on the website.”

http://www.foodforthebrain.org/content.asp?id_Content=1825

Prof. Salthouse’s contribution to the test is well validated within its usual sphere of use. Prof. Salthouse makes no claims for the integration of his test within the CFT and states that his comparison tests should not be treated as valid predictors of the risk of memory decline or the development of Alzheimer’s Disease. Under the circumstances, it is arguably imperative that the pilot studies and materials that underpin the “validation” of the CFT should be made available. However, the absence of accessible validation is not made clear to the public, nor, perhaps, to some NHS Commissioners who are given funding proposals for which there has not been adequate due diligence.

iii) Media coverage, Patrick Holford and the FFTB promoted the CFT as diagnostic of Alzheimer’s Disease or its prodrome when the CFT has not yet been publicly validated as an appropriate instrument to identify or quantify mild cognitive impairment.

David Smith modified those claims when challenged by Margaret McCartney. FFTB updated its website July 1 and, in line with Smith, has considerably modified its claims for the scope of the CFT:

“Does the CFT diagnose dementia, Alzheimer’s disease or Mild Cognitive Impairment?
No. The CFT is not a diagnostic test, but a test designed to inform/educate the user about their cognitive function. If the result is below a threshold we suggest that they visit their GP who can perform whatever diagnostic tests are required at their discretion.

However, both Patrick Holford and Food for the Brain promoted the CFT to their mailing lists: the former was headed, “15 minute free test to prevent dementia” and the latter “A 15 minute free test could stop you ever getting Alzheimer’s”. Why have neither Patrick Holford nor Food for the Brain issued corrections to their mailing lists to update them as to the reduced scope of claims for the test?

Allegedly, many people have taken this test. Perhaps the test-takers were reassured that it was developed at Oxford University, and that it is a validated test for Alzheimer’s and its prodromes. Patrick Holford claimed (in a later deleted blog post) that 55,000 people took the CFT in 10 days. Since then, FFTB has claimed that more than 70,000 people have taken this test.

A test that plainly was not developed by an “Oxford research team”. A test that is now said not to be a test for what people were told that it was but now “simply tells the user about their cognitive status” albeit the validation for that is not available.

Why hasn’t Oxford contacted media outlets such as Daily Mail and Telegraph to instruct them to correct their stories if Oxford’s involvement is as limited as the current version of the FFTB website implies? Were the pilot studies on which the ‘validation’ rests conducted at Oxford, and, if so, did Oxford oversee their clinical governance?

Why haven’t Patrick Holford or Food for the Brain alerted media outlets that they have modified their claims concerning: the provenance of the test; the scope of the claims for the CFT’s diagnostic purpose; and that the claims for validation ought to be held in abeyance until such time as the details are published?

Why haven’t Patrick Holford or Food for the Brain alerted their mailing lists as to these substantial revisions concerning the CFT? Has there been any attempt to contact GPs who’ve received one of these letters from a patient to inform them of the modified status of these claims? (The GP letter is still available on the FFTB site and still contains claims that are out of date.) If not, why not?

The CFT has created anxiety amongst some users and has given false confidence to others. Rather curiously, FFTB brags of the thank you letters it has received although it now seems as if they were being thanked for reassurances that can no longer carry any weight given the modifications and reduced scope of the claims for that test.

A curious test and a curious business. There will be more to come when more information is available about the ethical approval for this test and other pertinent matters.

Notes

[1] Sample quoted from

http://www.womanandhome.com/forums/showflat.php/Cat/0/Number/726038/Main/725925/

[Northwindrider] Mine said I was at low risk of developing Altzeimers which is quite comforting as I have a Grandmother with it and know that my Mum was in the early stages when she died.

[snowy47] I have completed the test and i have a very low chance of developing Altzeimers, my D passed last year and he put my M through hell with it.

[susieblue] I have just done the test and told I was low risk. But I am pretty sure my mother would have been told the same had she done it at my age too. Read an article about it on Yahoo. Complete rubbish! For starters my mother, aunt and uncle all had/have it.
[aec13cat] Was so curious in the end I took it but it shows I’m at risk -totally depressed now and wish I hadn’t taken it

Following from

http://forum.alzheimers.org.uk/showthread.php?33976-Someone-look-at-this-for-me-please

[Danny] I took the online test myself,I scored 37/110. It was a bit worrying to be told I could be at serious risk of developing Alzheimers. It has worried me to bits.It will teach me to stop researching so much.

[Tony] I just took that test and scored 29 yesterday
had my 6 monthly test for memory clinic scored 30/30 now I’m confused with the results was the memory clinic test 2 easy

[Gill66] I am suitably happy with a score of 88. Use a mouse, it’s a lot easier. With a history of dementia in the family i feel quite content this evening

Quoted from Patrick Holford’s blog:

“The positive response to my test results came as a great relief, as my father, uncles and paternal grandfather all developed symptoms of senile dementia of one form or another, when they were precisely the age I am now. I feel a great weight has been lifted from my shoulders, at least for the foreseeable future.” Yours, Hugh G. “A really informative website – and the opportunity to put my mind at rest by doing the cognitive test was priceless. I found the test itself very well introduced and explained. The examples are particularly helpful. I’m sure I’m not the only one who approached the test with some anxiety but I found I was far less panicked than I expected.” said Marion. Ivor, age 75, said “The nightmare of Alzheimers has been put to sleep by the results of this test. Thank you.”

http://www.patrickholford.com/index.php/blog/blogarticle/951/ – if no longer available, please see

http://www.freezepage.com/1307103965TWDDWXGIGE

It is worth noting that Ivor is outside the age range for the test yet Patrick Holford nonetheless includes this testimonial.

[2] “The Cognitive Function Test assesses three critical areas of cognitive processing associated with cognitive decline leading to Alzheimer’s disease…This test has been developed in collaboration with Dr Celeste de Jager from the University of Oxford, Professor Timothy Salthouse from the University of Virginia and Catharine Trustram Eve.”

Original link for text: http://www.foodforthebrain.org/content.asp?id_Content=1824

Freezepage for the page May 20 2011: http://www.freezepage.com/1305892729EKYIERRJCR

A similar claim is made in the results letter than test-takers are advised to give their GPs:

“Your patient has completed the Cognitive Function Test at http://www.foodforthebrain.org, an educational trust whose mission is to promote the link between mental health and nutrition. This is a validated screening test for those aged 50 and above, designed to detect early cognitive impairment. This test has been developed with Professor Timothy Salthouse and Dr Celeste de Jager, specialists in assessment of cognitive function.”

Original link for text: http://cft.foodforthebrain.org/doctors-letter-r.aspx?name=Patrick%20Holford&dob=4/5/1953

Freezepage for the page May 20 2011:
http://www.freezepage.com/1305892790UAAUYMCITZ

Daily Mail and other accounts credit “Dr Celeste de Jager, [as] the main developer of the Cognitive Function Test”.

http://www.dailymail.co.uk/news/article-1386912/15-minute-online-test-dementia-DIY-memory-quiz-detects-early-signs-Alzheimers-people-young-50.html

Patrick Holford blog post 15 Minute Online Test for Dementia:

“The test, available from http://www.foodforthebrain.org, also tells you how to delay memory decline and possibly reduce Alzheimer’s risk, based on research of people with mild cognitive impairment, the stage before Alzheimer’s, by Oxford University experts Professor David Smith and Dr Celeste de Jager.”

Freezepage for the page 20 May 2011: http://www.freezepage.com/1305892842FQLAHXZRQC

[3] “The Cognitive Function Test assesses three critical areas of cognitive processing associated with cognitive decline leading to Alzheimer’s disease…The test has been validated for the age range of 50 plus. ”

Original link for text: http://www.foodforthebrain.org/content.asp?id_Content=1824

Freezepage for the page May 20 2011: http://www.freezepage.com/1305892729EKYIERRJCR

The Daily Mail account of the CFT (in common with the Telegraph and other news outlets) explicitly claims that the test can detect early signs of Alzheimer’s which implies that the test is diagnostic.

“An early warning test for Alzheimer’s that can be taken online in 15 minutes has been developed by British scientists.
It can spot signs of the debilitating brain disease in people as young as 50.
The computer-based interactive quiz provides an instant result and could help delay or prevent the condition by advising simple diet and lifestyle changes.”…
“But most are still in the early stages of development and none, other than the new Cognitive Function Test, which has been devised by Oxford University scientists, can be taken online in the comfort of a person’s own home.
This is likely to make it popular with those who fear their memory is failing but are too embarrassed to discuss their worries with their doctor.

[B]ecause apparently healthy people have no way of telling if they are among those who could benefit from the vitamin B memory boost, the Oxford research team created the test.
It measures mild cognitive impairment – or the slight memory lapses that can be a precursor to Alzheimer’s – which affects one in six aged 70-plus, or 1.5million Britons. Half will develop dementia within five years of diagnosis.”

http://www.dailymail.co.uk/news/article-1386912/15-minute-online-test-dementia-DIY-memory-quiz-detects-early-signs-Alzheimers-people-young-50.html

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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

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Patrick Holford Promotes His Apocryphal Homocysteine Gospel in The News of the World

Patrick Holford on ITV Lunchtime 16 April 2008
Former Visiting Professor Patrick Holford is Head of Science and Education at Biocare who display the indulgence of peculiarly fond family members in declaring him to be an innovative thinker and expert despite the many faux pas and errors that have been highlighted in his work. Biocare must be delighted to have their most high profile media nutritionist’s work featured in News of the World (NotW): Look 10 Years Younger with the H-Factor. Continue reading

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Daily Mail and Its Frame of a Recent Homocysteine and Depression Study

Daily Mail regularly displays a remarkable similarity to the public writings of Visiting Professor Patrick Holford. It has taken time out from its usual project of dividing substances into things that will give you cancer or cure it, or similarly for diabetes to digress into the Holford obsession with over-claiming for the significance of homocysteine levels and the outcome of manipulating them. In a recent round-up, Daily Mail declared Vitamin B can beat ‘old age blues’. A little confusingly, the accompanying photograph is that of an attractive, well-turned out woman in her late 20s/early 30s or so. It’s distracting because the study was carried out in men over the age of 70. Continue reading

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Homocysteine: Really Not a Crystal Ball

Former Visiting Professor Patrick Holford is still Head of Science and Education at Biocare so presumably they must believe that he enhances their reputation and scientific credibility with his advocacy of tests such as those for homocysteine (Hcy) levels and recommendations that people with high levels (as defined by him) should lower it by taking various supplements (see related reading). Continue reading

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Polypills or Vitamins for Homocysteine and Cardiovascular Risks: the Hype is Ahead of the Evidence

You may have experienced déjà vu over the last few days if you’ve been reading excited accounts about polypills for the over-55s (there was a lot of Oh Brave New World about the potential for polypills in 2003). The claims are that polypills will prevent 100,000 premature deaths a year and also prevent up to 80% of heart attacks and strokes. The polypills will contain a cholesterol-reducing statin; three types of medicine to lower blood pressure (thiazide, aspirin and beta-blockers); and folic acid to reduce levels of homocysteine (Hcy). Continue reading

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BANT and Conflict of Interest: YorkTest and Similar Commission

BANT has a sufficiently flexible code of ethics that nutritional therapists are allowed to earn commission from selling tests and pills. That in itself is not particularly striking. What is unusual is that the therapist is under no obligation to declare this commission to the client (pdf):

In addition to supplying supplements as an integral part of a consultation, the Member may also act as a supplier of laboratory tests, or any other products related to Nutritional Therapy. The member may choose to benefit from trade discounts and commission payments when offered by the supplier on products purchased by him for such use. The member decides whether such payments, in whole or in part, are retained in his Nutritional Therapy business, or passed onto the client. [pg. 9; S 7.3 a); emphasis added.]

Continue reading

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Patrick Holford, Alzheimer’s Disease, Homocysteine Tests and Supplements

Professors Patrick Holford and David Smith chose the Daily Record to announce their remarkable findings that Alzheimer’s Disease is preventable with just a “few simple diet and lifestyle changes”.

I may be new to Holford Watch but I am familiar with the Holford Test-Em Dose-Em style of Jeopardy. If the answer is, “Dose them with B vitamins” the question must have been, “What do you do after testing someone’s homocysteine levels?”.  And, what do you know, I think it has slipped its way into this article, masquerading as a “simple blood test”. Continue reading

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How Relevant Are Holford’s Claims About Homocysteine Levels? Part 2

Patrick Holford gives a remarkable overview of history to support his claims for the value of homocysteine testing in helping you “to eliminate your risk of ever having a heart attack”. He swoops from autopsies on egyptian mummies to unsubstantiated opinions on the prevalence of heart disease in late 19th century America via some mangled statistics on the risk of premature death from cardiovascular disease in the UK, before alighting on a study of restenosis to justify his claims.

One of the most common surgical procedures for those with coronary artery disease is angioplasty. It involves inserting catheter tubing containing a small balloon into arteries around the heart. The balloon is inflated to flatten deposits of atherosclerotic plaques blocking the artery, so blood can once again flow to the heart.

Like bypass surgery, angioplasty is often not a permanent cure, and after surgery the arteries may reclog in the treated area – a very undesirable condition called restenosis…

Restenosis of the coronaries is much more likely if your H score is high, according to research at the Swiss Cardiovascular Centre in Bern. (4) In a nutshell, this means the higher your H score, the faster your coronary arteries will narrow again after surgery, so there’s little point having an angioplasty without testing for and treating high homocysteine.

Unfortunately, this is only part of the story; the role of homocysteine levels in predicting restenosis is not that straightforward. Holford has frequently expressed his concern about the mis-citing of research literature and possible suppression of inconvenient findings, so it seems appropriate to look at the research literature for homocysteine and restenosis in a little more detail to see if he is representing the literature in an evenhanded way.

Back in 2000, Dr. Steven Miner and his colleagues published an interesting study into possible correlations between homocysteine concentrations and restenosis following angioplasty. This was a well-designed, prospective study. The authors were confident in their conclusion that raised homocysteine levels do not predict the likelihood of restenosis.

The range of plasma homocysteine concentrations in this study is consistent with that seen in other studies,[refs] as is the trend toward an increased mean homocysteine concentration in homozygotes for the MTHFR 677T genotype.[ref] However, ours is the first published study to investigate the possible correlation between homocysteine concentrations and restenosis after PTCA and clearly shows the absence of any positive correlation. This lack of effect is apparent in patients undergoing PTCA alone and in with those receiving adjuvant stenting. No threshold effect is apparent. The adequate sample size, near complete follow-up, and the trend toward a negative correlation makes the possibility of a false-negative study extremely unlikely. [Emphasis added.]

There are several other studies that do not find a signficant relationship for homocysteine and restenosis:

2002 Relation of homocysteine, vitamin B(12), and folate to coronary in-stent restenosis “These results suggest that homocysteine, folate, and vitamin B(12) are not related to the angiographically determined rate of coronary in-stent restenosis after 6 months.”

2005 Clinician Update Homocysteine and Its Effects on In-Stent Restenosis cites a number of earlier clinical trials that fail to show a relationship between high homocysteine levels and restenosis. They note that several trials are in progress and conclude: “Until complete results of these studies become available, screening for hyperhomocystinemia in patients undergoing coronary stenting is only recommended in the case of premature atherosclerotic disease (patients homocysteine-lowering therapy might have a deleterious effect in patients treated with stent implantation“. [Emphasis added.]

2006 A prospective patient observational study of the role of hyperhomocysteinemia in restenosis in patients undergoing infrainguinal angioplasty or bypass procedures. “This study does not support the hypothesis that HHCy is associated with an increased risk of restenosis after vascular intervention.”

2006 Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. This is one of the studies that Holford acknowledges and disputes; however, the authors conclude: “Folic acid supplementation has not been shown to reduce risk of cardiovascular diseases or all-cause mortality among participants with prior history of vascular disease. Several ongoing trials with large sample sizes might provide a definitive answer to this important clinical and public health question”.

2006 Efficacy of folic acid therapy for prevention of in-stent restenosis: a randomized clinical trial. “Treatment with folic acid does not decrease the rate of restenosis and need for revascularization of the target lesion after stent-percutaneous coronary angioplasty.”

2006 Post-interventional homocysteine levels: failure as a predictive biomarker of in-stent restenosis. “[W]e hypothesise that homocysteine may not serve as a safe and independent biomarker of in-stent restenosis after a six months period following percutaneous coronary stenting.”

Holford uses a restenosis study that is not validated by other researchers to assemble a supporting platform of evidence to demonstrate the value of widespread testing of homocysteine levels.

Holford and Braly claim that homocysteine levels are a “chemical crystal ball”. It would be profoundly useful and cost-effective if homocysteine levels were capable of predicting the need for restenosis or could function as a simple index of your current and future health. Unfortunately, it doesn’t seem as if a homocysteine test can bear the mantle of so much responsibility: there isn’t even a consensus of opinion as to whether or not it has a predictive role for restenosis although the evidence is increasingly against it.

Regular homocysteine tests (as recommended 2-3 times a year to establish your baseline levels and tweak/maintain them with vitamin supplements) cost money; from around £70-75 per test. The recommended H Factors vitamin supplement will cost from £41.60 for 90 days to £41.60 for 30 days, depending on the recommended dose. There is no information about the bioavailability of the contents, so I don’t know if it is appropriate to expect your GP or Practice Nurse to advise you on your H Factors dosage; you might need to pay to consult a nutritionist or similar. A nutritionist might base his/her recommendations on an inappropriate interpretation of research and some unsupported beliefs.

You may well be comforted at the thought that your homocysteine levels are low or within bounds; however, it might be helpful if you are confident that there is good quality research to support the value of this. In subsequent parts of the review of Holford’s claims for homocysteine, we will look at trials that report that homocysteine levels can be reduced by vitamin supplementation but that this has no affect on clinical outcomes; e.g., you might spend between £700-1000 per year and successfully lower your homocysteine levels but still have raised blood pressure.

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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.

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