Why High Homocysteine Levels Matter and How to Optimize Them

Dr Mehmet Yildiz

Hyperhomocysteinemia is a severe health condition but might be treated with healthy lifestyle habits and professional support.

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Disclaimer: Please note that this story does not provide health advice. It is for information, inspiration, and awareness purposes based on reviewed papers from credible sources indexed in PubMed. 

Purpose of the Article

This article defines homocysteine, highlights the impact and implications of high homocysteine levels, and provides practical tips to lower the risks of hyperhomocysteinemia, leveraging guidance from scientific papers. I provide links to papers.

What is homocysteine?

Homocysteine is a sulfur amino acid existing in our bloodstream. It is a metabolite of methionine which is another amino acid. Elevated plasma homocysteine is called hyperhomocysteinemia in the literature.

This amino acid is processed by folate, vitamin B6, and vitamin B12 to create other biochemicals in the bloodstream. In addition, energy production in mitochondria seems to cause the effects.

For example, as documented in this paper, “recent studies suggest that the interaction between homocysteine and mitochondria is complex, and reactive oxygen species are possible mediators of homocysteine effects.”

The high levels of homocysteine in the bloodstream indicate vitamin deficiencies and lead to serious health issues, as I cover in the next section.

Health Implications of High Homocysteine Levels

Usually, between five to fifteen micromoles per liter (mcmol/L) of homocysteine is considered normal for healthy individuals.

However, if it gets higher than 50 mcmol/L for a prolonged time, it can damage the lining of arteries, cause blood clots or blood vessel blockages, and impact the oxygenation of the cells in the body.

As pointed out in this paper, “although new technologies have been developed over the past two decades that have enhanced the precision of measurement, universal guidelines for circulating homocysteine determination remain lacking.”

Damaged arteries are the root causes of cardiovascular diseases such as heart disease and strokes. Elevated homocysteine levels might also increase the risks of neurodegenerative disorders such as dementia.

Literature indicates that both high homocysteine levels and low folic and B12 levels in blood correlate with increased risk for Alzheimer’s disease.

Since cardiovascular disease and neurodegenerative disorders are widespread and cause morbidity and mortality, optimizing homocysteine levels can be a proactive health measure.

Symptoms of High Homocysteine Levels

Typical symptoms are fatigue, dizziness, weakness, changes in complexion, soreness in the mouth, and tingling in various parts of the body, such as hands, arms, and feet.

When patients have these symptoms usually, family doctors can order blood tests to check homocysteine levels and vitamin deficiencies for folate, B6, and B12.

When I had vitamin B12 deficiency in my younger years, my homocysteine levels were higher than the normal range. Solving the deficiency optimized my levels.

What are the risk factors, and how to address them?

The contributing risk factors are vitamin deficiencies caused by folate, B6, and B12, existing heart conditions, and genetics.

The genetic factor known as homocystinuria is a rare condition. People having this condition cannot process the amino acid methionine properly.

The risks of elevated homocysteine levels are blood clots, heart disease, heart attack, stroke, osteoporosis, and dementia.

The risk factors can be lowered by addressing vitamin deficiencies, making lifestyle changes, and treating them using some supplements or medication prescribed by qualified healthcare professionals.

In addition to increasing B6, B12, and folate via diet, healthcare professionals also provide guidance on supplementing these vitamins. In my case, B12 injection and sublingual supplementation helped. Later, my diet provided adequate B12.

When I asked my cardiologist during those years to optimize my homocysteine levels, he highlighted the importance of exercise that can lower blood pressure. He wanted me to lower sodium a bit.

The cardiologist particularly asked whether I smoked but fortunately, I did not. So smoking might increase the risks for this condition. Therefore, permanently quitting cigarette smoking is a proactive health measure.

TMG as a Promising Supplement to Lower Homocysteine Levels

I learned more about homocysteine from a friend who specialized in researching a molecule called TMG (trimethylglycine).

TMG is a well-documented supplement, also known as betaine. It is available over the counter in many countries. I documented my research of this molecule in an article titled "Here’s How TMG Supplementation Might Improve Four Health Conditions." Interested readers might find it via a Google search. 

As documented in the article, TMG looks promising for improving cardiovascular, metabolic, mitochondrial, and mental health while improving fitness performance. Betaine promotes healthy homocysteine levels.

With guidance from my scientist friend, I reviewed the literature and found evidence that TMG supplementation might optimize the homocysteine levels. Instead of citing many papers, I choose two metanalysis covering notable papers.

This meta-analysis in the Journal of Chiropractic Medicine informs that “Supplementation with at least four g/d of betaine for a minimum of six weeks can lower plasma homocysteine.”

This meta-analysis included five randomized controlled trials published between 2002 and 2010 identified using MEDLINE.

However, as pointed out in this review, “controversy regarding the effects of betaine supplementation on cardiovascular markers has persisted for decades.”

This 2021 systematic review and meta-analysis published in the Critical Reviews in Food Science and Nutrition journal supported “the advantage of a lower dose of betaine supplementation (<4 g/d) on homocysteine concentrations without the lipid-augmenting effect observed with a higher dosage.”

Other Supplements to Optimize Homocysteine Levels

Apart from TMG, folate, B6, and B12, zinc might also contribute to optimizing homocysteine levels. I documented my perspective on Zinc in a story titled Zinc Is an Essential Mineral and Its Deficiency Matter for Health. It can be found via a Google search. 

I also came across the benefits of increasing glutathione levels especially supplementing with NAC (N-Acetyl-Cysteine). I documented my findings and perspectives on glutathione and NAC in two blog posts. Titled Three Tips to Maintain Healthy Glutathione Levels Naturally and Here’s Why N-Acetyl Cysteine Is a Vital Molecule for Health.

Conclusions and Takeaways

Homocysteine is a naturally materializing amino acid in the bloodstream. It is part of the body’s methylation process. However, elevated levels indicate the risks of cardiovascular and neurodegenerative disorders.

Since cardiovascular diseases such as heart attacks and strokes and neurodegenerative disorders such as dementia are widespread and cause morbidity and mortality, optimizing homocysteine levels can be a proactive health measure.

When we experience symptoms such as fatigue, dizziness, weakness, yellow skin, sore mouth, and tingling in various body parts, we might get it checked via blood tests. High levels can be treated with supplementation and simple lifestyle changes.

Thank you for reading my perspectives. I wish you a healthy and happy life.

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I write about important and valuable life lessons. My goal is to delight my readers. My content aims to inform and engage my readers. I'm a technologist, cognitive scientist, and postdoctoral researcher, with four decades of experience.

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