Key Takeaways:

1. Homocysteine levels are a useful biomarker that can be measured via a blood test. 
2. Elevated homocysteine is associated with an increased risk of both cardiovascular and cognitive disease.
3. Specific B-Vitamins have been shown to lower homocysteine levels.
4. Homocysteine can be influenced by your diet and lifestyle.

How many times have you been to your local doctor and the doctor has said that your blood test result is “normal” – yet, you still feel low energy, or that something is just not quite right? 

You see, there are a range of health markers that you SHOULD pay close attention to for optimal health and performance. One of these is homocysteine.

Elevated homocysteine can be a sign of key nutritional deficiencies, and is associated with an increased risk of various diseases including cardiovascular disease and cognitive diseases such as dementia! In this article, we explore what homocysteine is, how it’s produced, and its key roles in the body. We will also take a deeper dive into how homocysteine affects the brain, and what can be done to both increase and decrease this substance.

What Is Homocysteine?

Let’s first breakdown a little about this substance. Homocysteine is a natural substance made by the body, not to be feared, but to be respected and controlled. Homocysteine functions as a metabolic crossroad that can affect all the methyl and sulfur group metabolism of key enzymes, hormones, and vital nutrients. Many important nutrients, especially B vitamins, are required for these enzymes.

How Is It Produced?

Its Role In The Body:

Homocysteine plays an important metabolic role, but too much is toxic and too little results in metabolic problems. This seems true of so many metabolites in the body. They play key roles in physiological function, but when outside of a typically narrow range, problems arise. The problem is not the molecule, but what happens when the molecule is damaged or outside of their healthy parameters. Interestingly, these issues are typically not the result of ingestion of the molecule, but rather physiological dysfunction around them. In the case of homocysteine, the ideal range is 5.0 to 7.0 mmol/L (as measured via a blood test).

Homocysteine is converted in the body to cysteine, with vitamin B6 facilitating this reaction. Cysteine is an important amino acid in the body that has many roles, one of which is essential for detoxification. Homocysteine can also be recycled back into the essential amino acid methionine using vitamin B12-related enzymes. Methionine is associated with detoxification and innate immune function amongst other things.   

Dangers of Elevated Homocysteine:

Excess homocysteine in the circulation can damage the lining of arterial walls so they become narrow and inelastic. At high levels, homocysteine is inflammatory and neurotoxic; damaging the nervous system and increasing oxidative stress. It’s also been shown to contribute to mitochondrial damage and reduce energy production in the brain. Researchers have found that high levels of homocysteine disrupt the integrity of the blood-brain barrier, allowing substances that are normally kept out of the brain to cross over and contribute to neurological problems. Other studies have found that people with high levels of homocysteine have lower levels of serotonin and SAMe, a nutrient involved in the production of many neurotransmitters that improve mood. Considering all this, it’s not too surprising that high levels of homocysteine has been linked to many chronic neurodegenerative, inflammatory, immunological and neuropsychiatric diseases. The below diagram summaries other pathologies in which elevated homocysteine can play a fundamental.

How Homocysteine Affects The Brain:

Homocysteine has been implicated as a risk factor for vascular disease as well as brain atrophy. There is evidence that homocysteine increases oxidative stress, DNA damage, thus triggering apoptosis and excitotoxicity, all important mechanisms in neuro-degeneration. Homocysteine is also prothrombotic (increases the risk of blood clots) and proatherogenic (promotes the formation of fatty deposits in the arteries), and causes damage to blood vessel walls. This can all lead to brain atrophy in older individuals, and possibly to white matter hyperintensities (WMH) in the brain. Epidemiological evidence and longitudinal data support homocysteine as a risk factor for cognitive impairment and Alzheimer’s Disease (AD).

What Increases Homocysteine?

The main cause of elevated homocysteine is usually B-Vitamin deficiency. Specifically, B6, B9 (folate) and B12. Deficiency in these B vitamins can be the result of poor dietary habits or genetic mutations, such as the relatively common MTHFR gene mutations which impact correct folate metabolism and utilisation. Common genetic mutations are why it’s so important to ensure correct supplementation when considering a B-Vitamin. Most common B-complex supplements on the market today contain cheap synthetic forms of B vitamins that are not readily (if at all) absorbed by people with these common genetic mutations, as their bodies don’t produce the enzymes crucial to their metabolism. 

Other factors associated with elevated homocysteine levels include:

• A family history of elevated blood homocysteine.
• Age – Blood homocysteine levels rise with age in both men and women.
• Gender – Blood homocysteine levels are higher in men than in women. The reason for this is not totally understood but may be related to differences in muscle mass, hormones, or kidney function.
• Kidney Disease – The level of homocysteine in the blood increases in kidney disease because the kidneys stop properly filtering homocysteine from the blood.
• Medication Use – Certain medications increase blood homocysteine levels. These medications include anticonvulsants (such as phenytoin), methotrexate, cyclosporine, levodopa, theophylline, niacin, and cholestyramine.

What Decreases Homocysteine?

1. Eat A Balanced Diet – Homocysteine tends to be highest in people who eat a lot of animal protein but consume low quantities of fruits and leafy vegetables, which provide the folic acid and other B vitamins that help the body rid itself of homocysteine.
2. Take A Supplement – Correct supplementation with a quality ‘active form’ B-Vitamin complex.
3. Get Regular Exercise – Exercise can increases homocysteine in the short-term, but in the long term, it is associated with lower homocysteine levels.
4. Manage Stress Levels – Although the link between stress and homocysteine is not quite clear, several studies have found that stress can increase homocysteine levels.
5. Reduce Alcohol Consumption – Daily alcohol increases homocysteine levels.

Takeaway

Elevated homocysteine levels (hyperhomocysteinemia) is a recognised risk factor for many diseases including cardiovascular and neurological conditions. The good news is that lifestyle modification and supplementation of ‘active forms’ of B-vitamins, specifically folate (B9), B12 and B6, has proven to be effective in managing homocysteine levels.

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Deminice R, et al. The Effects of Acute Exercise and Exercise Training on Plasma Homocysteine: A Meta-Analysis. PLoS One. 2016 Mar 17;11(3):e0151653. 

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