Homocysteine

What is homocystiene?

Homocysteine is an amino acid. It is part of the same group of amino acids as cysteine. Homocysteine is not derived from the human diet but is instead synthesized directly in the body from methionine.

The role of homocysteine in the body is to aid cellular metabolisation and protein manufacture. There are millions of cells within the body and they require energy to continue to perform their proper function, the production of this energy is cellular metabolisation.

Homocysteine was originally discovered in 1931, however it was the work of a Harvard based scientist named Dr. Kilmer McCully in the 1960’s that first proposed a link between elevated levels of homocysteine and heart disease and strokes. He observed that unfortunate young children with such diseases showed high levels of homocysteine, up to 300 micromoles per litre (µmol). Normal levels would generally be below 7µmol. Based on this research he suggested that elevated levels of homocysteine were also a risk factor for heart disease in the general population. This was heavily criticised and little progress was made to publisise this.

In a typical homocysteine test normal levels can be described as ranging between 5-15µmols, however research has suggested that levels as low as 9µmols can produce a threefold increase in cardiovascular risk escalating sharply at levels as “normal” as 15µmols.1 So when the test indicates normal, check what normal really refers to. As in many nutritional scenarios, look at what is optimum rather than what is normal.

Generally heart disease and particularly atherosclerosis are deemed to be degenerative processes of plaque accumulation in the arteries and hence ones that only affect older people.

The Effects Of Raised Homocysteine Levels

Blood is pumped by the heart through a network of blood vessels. The blood vessels are comprised of arteries carrying nutrient rich blood from the heart, capillaries (where the nutrient are absorbed into the body tissue) and veins (where the blood is returned to the heart). These blood vessels are lined with a thin layer of cells called endothelium. This lining reduces turbulence in the blood allowing it to be transported further and easier around the body.

Homocysteine is understood to degrade the endothelium lining of the blood vessels in several ways.

Firstly homocysteine induces the growth of vascular muscle cells which are key components of atherosclerotic plaque.2  Raised homocysteine levels also promote increased levels of interleukin-8 and monocyte chemoattractant protein-1, both of which are proteins and responsible for attracting inflammatory cells into the arterial walls. Inflammation drives injury and plaque rupture which leads to heart attack.3-4

Elevated homocysteine is also believed to increase the oxidation of LDL low density lipoproteins.

Finally raised homocysteine may also promote blood clot formation. Blood clot formation is the final step leading to a heart attack following a plaque rupture. Plaque is a collection of white blood cells and lipids that form in the arterial walls, sometimes referred to as fatty deposits.

The Effects of Nutrition On Homocysteine Levels

Much recent research has been focused on effective methods to lower homocysteine levels in the body. Inevitably a great deal of this work has focused on nutritional methods.

The association between raised homocysteine levels and vascular disease is so overwhelmingly strong that most authorities agree that treatment of elevatated levels is both necessary and wise. However when it comes to research into the effects of nutritional supplementation, the case is not definitive.

Almost all of the clinical trials undertaken are focusing on supplementation with folic acid (B9), pyridoxine (B6) and cobalamin (B12). There is a also significant research into supplementation with trimythylglycerine (betaine)  and choline. These last two nutrients are used to augment the vitamins and reduce post meal surges in homocystine that are not fully controlled by B-vitamins alone.

The suggested level of supplementation will vary with individuals, however as a guide the starting level for folic acid (B9) is 800mcg.6 For B6 the level is not as clear. B6 is particularly effective at preventing post meal surge and levels from 2-50mg are used and even up to 100mg with clinical supervision. However the Dutch are particularly experienced in homocysteine research and their studies routinely use levels of 250mg with no ill effect. For vitamin B12, levels of around 250mcg are suggested.7 

Trimythylglycerine (TMG) is found naturally in our diet in food like quinoa, wheat bran, spinach and sugar beet products, however supplementing around 2000mg per day is thought to be very effective at suppressing post meal surges in homocysteine.8 However there is also evidence to suggest that excessively high level of TMG can increase levels of LDL cholesterol, so this should also be tested for those on higher levels of TMG.

Choline is broken down in the body to trimythylglycerine and is also found naturally in the food we eat. A suggested supplement of between 400mg – 600mg is advised based on the research conducted to date.9

Other Interventions And Strategies To Control Homocysteine Levels

You may recall at the start of this article that homocysteine is synthesied in the body from methionine. Although methionine is an essential amino acid excessively high levels may also raise homocysteine levels.10 Methionine is found in large quantities in red meats, so it is advisable to keep levels of red meat in your diet to sensible, moderate levels and enjoy a balanced diet. Dairy products also contain high levels of methionine.

Fish oils have been shown to have a moderate effect on lowering homocysteine levels. Given the evidence linking raised homocysteine and vascular disease and the other numerous health benefits of fish oil supplementation, it would seem sensible advice for most people consuming a western diet to take a good quality fish oil supplement on a daily basis.

Women tend to have lower levels of homocysteine than men during the reproductive stage of their life. This fact and the protective benefits of estogen in women may help to explain why women tend to suffer heart attacks on average 10-15 years later than men.

Hereditary factors will also mean higher levels of homocysteine in up to 10% of the population. 

There is also clinical research to suggest that the normal levels of homocysteine are higher in vegetarians and that this group also tend to show lower levels of vitamin B12.11

Exercise and Homocysteine

The limited research carried out in this area may appear conflicting; however as with any exercise based research benefits are generally derived from what we would broadly term normal exercise levels. Extremes of exercise bring their own risk factors.

With regards to homocystiene, research carried out on cardiac patients has demonstrated a  reduction in homocysteine levels of around 12% following a program of regular exercise.12 However there is also research that suggests an increase in homocysteine levels in those undertaking intense, long duration exercise.13 This is possibly due to the increased load on  methionine metabolisation.

Monitoring Homocysteine Levels

Given all of the evidence above it would seem advisable for people to test their homocysteine levels in the same way that we are encouraged to monitor cholesterol. This can be performed via a simple blood test that you can conduct yourself. The result can then be sent off for analysis and you will receive your results in about one week’s time. York Test provides a simple DIY kit as described above or your doctor may undertake it for you.

Conclusion

To balance the views expressed above, there is also a degree of clinical research to suggest that supplementation with B-vitamins and other nutrients may have little or no effect on preventing vascular disease even if homocystiene levels drop.14 

However no research suggests that supplementation causes any risks or adverse side effects. There are so many variables to consider that further research will be required to provide a more definitive answer. What is clear is that supplementation has been shown to successfully lower homocysteine levels and raised homocysteine is a clear risk factor in vascular disease. 

All authorities agree that stopping smoking, undertaking moderate exercise and lowering excessive body fat levels clearly reduce risk. Of course the other key factor to monitor is the content and quality of your diet, of which supplementation in some form may be a critical component.