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Homocysteine - Your Most Vital Statistic

by Patrick Holford and Dr James Braly(more info)

listed in nutrition, originally published in issue 94 - November 2003

Forget your blood pressure, your cholesterol, even your weight. There is one statistic that can determine better than any other, whether you will live long and healthy, or die young. It's called homocysteine.

Homocysteine is a type of protein, produced by the body and found in the blood that, ideally, should be present in very low quantities.

However, if you are not optimally nourished, homocysteine can, and does, accumulate, increasing risk of over 50 diseases, including heart attacks, strokes, certain cancers, diabetes, depression and Alzheimer's disease. One in two people in Britain have high homocysteine levels and one in two people die from preventable diseases. The question is, which one are you? The good news is that this new and important risk factor can be reversed in weeks.

What is Homocysteine?

Homocysteine is produced from the amino acid methionine, which is found in normal dietary protein. The trouble is, if you don't have optimal amounts of B vitamins in your diet, the enzymes that then turn homocysteine into either glutathione, which is the body's most important antioxidant, or SAMe (s-adenosyl methionine), which is the body's most important 'methyl donor', a very important type of 'intelligent' nutrient for both brain and body, don't work well enough, so homocysteine levels go up. (See Figure 1.) Also, it has been discovered that one in ten people have an inherited genetic mutation that makes them more prone to high homocysteine. This means that the Methylene-tetrahydrofolate reductase (MTHFR) enzyme that converts homocysteine into SAMe doesn't work so well. This means one in ten people need much larger daily intakes of B12 and folic acid to stay healthy.

Figure 1 – The Homocysteine Pathway
Figure 1 – The Homocysteine Pathway

While the importance of antioxidants is now well established, an important new concept in medicine is 'methylation'. The ability for the body to maintain chemical balance hinges upon its ability to add or subtract molecules called methyl groups. This is how the body turns one thing into another. To make this real, let's say all this talk of 'premature death' is stressing you out. Your body responds by adding a methyl group to noradrenalin to produce adrenalin. On hearing that homocysteine levels are rapidly reversible you relax. The body responds by removing a methyl group from adrenalin, turning it into noradrenalin. This kind of chemical reaction occurs countless times every second, keeping everything in balance.

If there was one measure of your antioxidant 'IQ' it would be the level of glutathione inside your cells. All those antioxidants you eat and supplement every day have the greatest effect if they ultimately raise intra-cellular glutathionine. Similarly, if there was one measure of your methyl 'IQ' it would be the level of SAMe inside your cells. This is because SAMe can easily donate a methyl group, or accept one back, keeping the body's biochemistry flexible. Normally, both SAMe and glutathione are made from the amino acid methionine in our diet, via homocysteine. However, if the conversion of homocysteine is blocked in any way, homocysteine levels go up and SAMe and glutathione levels go down.

This is only half of the bad news. The other half is the discovery that homocysteine damages your arteries, brain and DNA itself. That's why your homocysteine level is theoretically the most important indicator of the health and adaptability of your body's total biochemistry, and your risk of degenerative diseases. But where's the hard proof?

Heart Attacks and Strokes

The largest review of 92 studies, by David Wald and colleagues from the Department of Cardiology at Southampton General Hospital, recently published in the British Medical Journal, examined the association between homocysteine and risk of cardiovascular disease in 20,000 people.

They found that, with every five unit increase in homocysteine measured in the blood, the risk of heart disease went up 42% in those with the MTHFR gene mutation and 32% in those without. The risk for strokes went up 65% in those with the genetic mutation and 59% for those without. The researchers concluded that these "highly significant results indicate strong evidence that the association between homocysteine and cardiovascular disease is causal".[1]

This means that having a high homocysteine level isn't just associated with higher risk, it actually causes heart disease – a conclusion that is also being reached by other research groups.[2] This means that if you can lower your homocysteine level (your H score) you remove a key cause, and hence diminish the risk.

While the average homocysteine level is around 10 units, an ideal level is below six units. Those with a history of cardiovascular disease often have a level above 15 units. According to this study, this means that lowering a high homocysteine from 16 to six units – a 10 point drop – could cut risk significantly! This is not only much more substantial a reduction than cholesterol, it's also more achievable. How? With nutrients, not drugs.

Cancer – Cut Your Risk by a Third

Research published in the New England Journal of Medicine describing a study involving 45,000 pairs of twins, found that cancer is more likely to be caused by diet and lifestyle choices than by genes. Identical twins, who are genetically the same, had no more than a 15 per cent chance of developing the same cancer. This suggests that the cause of many cancers is largely environmental – that is, down to factors such as diet, lifestyle and exposure to toxic chemicals. This study found that choices about diet, smoking and exercise accounted for 58 to 82 per cent of cancers studied.[3]

So where does homocysteine come into all this? Cancer is triggered by damage to DNA – having a high homocysteine level means your DNA is more vulnerable to damage and more poorly repaired once damaged. At the other end of the scale, high homocysteine has been found to be a very good indicator of whether cancer therapies are working. The homocysteine level rises when tumours grow, and falls when they shrink. Forms of cancer already clearly linked to high homocysteine include cancer of the breast and colon and leukaemia, among others. Low homocysteine is likely to reduce your risk of these by a third. Coupled with other diet and supplement changes, you should be able to cut your cancer risk by substantially more than half.

Diabetes – Lower Your Risk

Type II, or adult-onset, diabetes is highly preventable. Yet more and more young people are developing it. The obesity 'epidemic' in the West has helped fuel this rise. If you are obese, the risk of developing diabetes goes up 77 times! Diabetics are at risk of having high homocysteine because we now know that the abnormally raised insulin seen in most diabetics stops the body from lowering and maintaining a healthier homocysteine level. By following a homocysteine lowering diet plus supplements, you will be able to help to reduce your risk of diabetes or, if you are diabetic, you'll be able to help keep it under better control and reduce complications.

Alzheimer's – Halve Your Risk

The evidence indicates that if you can lower your H score, you will significantly lower your risk of getting Alzheimer's. Homocysteine is strongly linked to damage in the brain. Dr Matsu Toshifumi and colleagues at Tohoku University, Japan, conducted brain scans on 153 elderly people and checked them against each individual's homocysteine level. The evidence was crystal clear – the higher the homocysteine, the greater the damage to the brain.[4]

A recent study in the New England Journal of Medicine charted the health of 1,092 elderly people without dementia, measuring their homocysteine levels. Within the next eight years, 111 were diagnosed with dementia. Eighty-three of this group were diagnosed with Alzheimer's. Those with high blood homocysteine levels (in this study, above 14 units) had nearly double the risk of Alzheimer's. All this strongly suggests that following a homocysteine lowering regime should significantly decrease your risk of developing Alzheimer's in later years.[5]

Halve Your Risk of Death from All Causes

Extraordinary findings from a comprehensive research study at the University of Bergen in Norway were published in 2001 in the American Journal of Clinical Nutrition.6 They measured the homocysteine levels of 4,766 men and women aged 65 to 67 back in 1992, and then recorded any deaths over the next five years, during which 162 men and 97 women died. They then looked at the risk of death in relation to their homocysteine levels. Remarkably, they not only reconfirmed the relationship between heart attacks, strokes and high homocysteine, but also found that "a strong relation was found between homocysteine and all causes of mortality". In other words, homocysteine is an accurate predictor of how long you are going to live, whatever the eventual cause of death may be!

With every five-point increase in H score, researchers found:

• 49% increased deaths from all causes;
• 50% increase in cardiovascular mortality;
• 26% increase in deaths from cancer;
• 104% increase in deaths from any causes other than cancer or heart disease.

If you are already in your fifties or sixties, you might be tempted to view all this news with gloom. But with a guaranteed solution the news is all good, because you can begin to do something about it right now.

Measuring Your Homocysteine

Your homocysteine level is easy to measure at home. Yorktest Laboratories (For details see Further Information) offer a home test kit that works from a pin prick of blood. You put a drop of blood onto a card, which separates and stabilizes the plasma portion of the blood. (See Figure 2.) You then send in your card and you'll know your H score within days.

Figure 2 – The Homocysteine Test
Figure 2 – The Homocysteine Test

Homocysteine is measured in mmol/l. We used to think a 'high' level was above 15 units. This is what increases your risk of a heart attack and doubles your Alzheimer's risk. But now, levels as low as 7 units are being linked to increased disease risk. Basically, there's no safe level and no guarantee that the diet and supplements you are currently taking is keeping homocysteine at bay. Up to 30% of people with a history of heart disease have a homocysteine level above 14 units. The average level in Britain is 10.5. What you want is a level below 6 units. This equates to superhealth. If you have any of the associated risk factors above it's especially important to get tested.

High Homocysteine Risk Factors

The risk factors for high homocysteine include:

• Genetic inheritance meaning family history of heart disease, strokes, cancer, Alzheimer's, schizophrenia, diabetes;
• Folate intake of less than 900 mcg/day;
• Increasing age;
• Male sex;
• Oestrogen deficiency;
• Excessive alcohol, coffee or tea intake;
• Smoking;
• Lack of exercise;
• Hostility and repressed anger;
• Inflammatory bowel diseases (Coeliac's, Crohn's, ulcerative colitis);
• H. pylori-generated ulcers;
• Pregnancy;
• Strict vegetarian or vegan;
• High fat diet/excessive red meat, high fat dairy intake;
• High salt intake.

Lowering Your Homocysteine Level

The good news is that, whatever your homocysteine level is, you can lower it with the right combination of nutrients and dietary changes, together with lifestyle changes designed to reduce your risk. Follow the H Factor Diet below.

The Ten-Step H Factor Diet

Eat Less Fatty Meat, More Fish and Vegetable Protein

Eat no more than four servings of lean, unfried meat a week, fish at least three times a week and, if you're not allergic or intolerant, a serving of a soya-based food (such as tofu, tempeh or soya sausages) or beans, such as kidney beans, chickpea hummus or baked beans, at least five times a week.

Eat Your Greens

Have at least five servings of fruits or vegetables a day. This means two pieces of fruit every single day, and three
servings of vegetables. Vary your selections from day to day. Make sure half of what's on your plate for each main meal is vegetables.

Have a Clove of Garlic a Day

Either eat a clove of garlic a day, or take a garlic supplement every day. You can either take garlic oil capsules or powdered garlic supplements.

Don't Add Salt to Your Food

Don't add salt while you're cooking or to the food on your plate. The only salt we consider healthy is Solo salt, which has half the sodium and lots of potassium and magnesium. Use this in moderation instead.

Cut Back on Tea and Coffee

Don't drink more than one cup of caffeinated or noncaffeinated coffee or two cups of tea a day. Instead choose from the wide variety of herbal teas and grain coffees available.

Limit Your Alcohol

Limit your alcohol intake to no more than half a pint of beer or one glass of red wine a day. Ideally, limit your intake to two pints of beer or four glasses of wine a week.

Reduce Your Stress

If you are under a lot of stress, or find yourself reacting stressfully much of the time, make a decision to reduce your stress load, both by changing the circumstances that are giving you stress and by changing your attitude. Simple additions to your life, such as yoga, meditation and/or exercise, or seeing a counsellor if you've got some issues to resolve, can make all the difference.

Stop Smoking

If you smoke, make a decision to stop and seek help to do it. There is simply no safe level of smoking as far as homocysteine and your health is concerned. Smoking is nothing less than slow suicide. The sooner you stop the longer you'll live.

Correct Oestrogen Deficiency

If you are postmenopausal, or have menopausal symptoms or other menstrual irregularities, check your oestrogen and progesterone levels with a hormone saliva test. If you are oestrogen or progesterone deficient, you can correct this with 'natural progesterone' HRT, in the form of a transdermal skin cream. Natural progesterone has none of the associated risks of HRT and your body can make its own oestrogen from progesterone.

Supplement a High-Strength Multivitamin Every Day

Take a high-strength multivitamin and mineral supplement, providing at least 25mg of the main B vitamins, 200mcg of folate and 10mcg each of B12 and B6, plus A, D, E and the minerals magnesium, selenium, chromium and zinc. Also supplement 1g of vitamin C for general health and the specific homocysteine lowering nutrients.

Homocysteine Supplements

The most powerful, and quickest way to restore a normal H score, below 6 units, is to supplement specific homocysteine lowering nutrients. These include vitamins B2, B6, B12, folic acid, tri-methyl glycine (TMG) and zinc. See Table 1 for guidelines:

The current vogue is to recommend folic acid, but this alone is far less effective than the right nutrients in combination. The amount you need also depends on your current homocysteine level. One study found that h scores reduced by 17% on high dose folic acid alone, 19% by B12 alone, 57% by folic acid plus B12 and 60% with folic acid, B12 and B6.7 All this was achieved in three weeks!

However, even better results would have been achieved by including trimethyl glycine (TMG). TMG is the best 'methyl donor' to supplement, better than SAMe. This is because only it can immediately donate a methyl group to homocysteine, thus detoxifying it. (See Figure 3.)

The Methyl Donor
The Methyl Donor

In a study in New Zealand, the H score of patients with chronic kidney failure and very high homocysteine levels was reduced by a further 18% when 4g of TMG was given, along with 50mg of B6 and 5,000mcg of folate, compared to patients taking just B6 and folate.[8] Some companies produce combinations of these nutrients such as Solgar's Homocysteine Modulators or Higher Nature's H Factors. These are the most cost-effective supplements for restoring a healthy homocysteine level.

The combination of the supplements recommended above, plus the diet, has the potential to halve your homocysteine score in weeks. The goal is to bring your H score below 6. Mine is 4.5. It is probably the best, objective measure of whether you are achieving optimum nutrition for you.

References

1. Wald DS and Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 325: 1202. 2002.
2. Clerk M et al. 'MTHFR 677C>T Polymorphism and Risk of Coronary Heart Disease'. JAMA. Vol. 288(16): 2023-2031. 2002.
3. Lichtenstein P et al. Environmental and Heritable Factors in The Causation of Cancer. New England Journal of Medicine. 342(2): 78-85. 2000.
4. Toshifumi M et al. 'Elevated plasma homocysteine levels and risk of silent brain infarction in elderly people'. Stroke. 32: 1116. 2001.
5. Seshadri S et al. 'Plasma homocysteine as a risk factor for dementia and Alzheimer's disease'. New England Journal of Medicine. 346(7): 476-483. 2002.
6. Vollset SE et al. 'Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocsyteine Study'. American Journal of Clinical Nutrition. 74(1): 130-136. 2001.
7. Koyama K et al. 'Efficacy of methylcobalamin on lowering total homocysteine plasma concentrations in haemodialysis patients receiving high-dose folate supplementation'. Nephrol Dial Transplant. 17: 916-22. 2002.
8. McGregor et al. 'Betaine supplementation decreases post-methionine hyperhomocysteinemia in chronic renal failure'. Kidney Int. 61(3): 1040-1046. 2002.

Further Information

The Homocysteine Test is available from Yorktest Laboratories Tel: 0800 074 6185; www.yorktest.com

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About Patrick Holford and Dr James Braly

About the Authors Patrick Holford and Dr James Braly are co-authors of the H Factor Diet (Piatkus £8.99). Patrick Holford may be reached on pat@patrickholford.com For further information see www.thehfactor.com

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