Category Archives: Refsum

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.



Filed under folate, folic acid, H Factors, home test, homocysteine, james braly, patrick holford, Refsum, restenosis, vitamin B12, vitamins

Homocysteine: Helpful or Hoax Asks Patrick Holford

I was disappointed in the quality of evidence that Patrick Holford put forward to support his claims that we could learn, How to Eliminate Your Risk of Ever Having a Heart Attack. Since then, I’ve been reading through the intervention trials that have experimented with lowering homocysteine levels through supplementation etc. and whether they have succeeded in lowering those levels, but not the incidence of clinical disease. Ultimately, it is more relevant to consider whether you have decreased the incidence of disease or reduced its severity rather than concentrating on a particular measurement. When you alter a particular measurement such as a cholesterol or homocysteine level, but you don’t reduce the incidence of (say) heart attacks or strokes, then it raises the suspicion that you have identified a false surrogate endpoint.

So, I was more than a little interested when I came across Holford’s article, Homocysteine: Helpful or Hoax? I don’t fully agree with his conclusions but it is a shame that he doesn’t link to this less dogmatic article from the one where he claims that

Lowering your H score…dramatically reduces the risk of death from all causes, not just heart attacks.

Holford is aware of trials that don’t support his conclusions and discusses those results with particular reference to the objections made by Dr. Helga Refsum. This discussion does, of course, include the use of a rhetorical device:

So was this a cover-up of the sort all too common with inconvenient findings in drug trials?

Somewhere in there, the fine nuance of Refsum’s arguments is lost. Holford quotes Refsum:

If we are going to optimise treatment for heart disease patients we need to discover what works for them and what doesn’t…The problem is that the trials so far are too small to come forward with definite advice.

It could also be argued that the trials, so far, are insufficient to support Holford’s broad recommendation for testing and supplementation in asymptomatic individuals.

In the light of his recent objections and comments about folate fortification (here and here), it is worth mentioning that Holford quotes Refsum on this:

The business of folate fortification…may also be affecting the results. Since it was introduced, stroke rates in North America have dropped significantly – by 10% in the USA and by 15% in Canada. “Translated into British terms,” says Dr Refsum, “those figures suggest that adding folate to the diet could actually save more than 5000 lives a year.” [Emphasis added.]

There is considerably more to say on the matter but it may well be premature (at best) to recommend that large-scale homocysteine screening and ‘corrective’ supplementation would “eliminate your risk of ever having a heart attack”. The evidence isn’t satisfactory or sufficient for people who have already had heart attacks and it has certainly not been adequately established for people who are asymptomatic. Helpful or hoax – who knows? Overhyped on the basis of current evidence – that’s a different question.


Filed under folate, folic acid, fortification, homocysteine, patrick holford, Refsum, supplements