A note on homocysteine optimization

The human body is enveloped with complex physiology, and revitalizing it is essential for a vibrant life. A significant part of this begins with understanding your baseline physiology—acquiring the right lab tests and cultivating insight into their implications for your health. One particularly important test that may seem unfamiliar to many is measuring blood levels of homocysteine. Homocysteine levels are often discussed as a biomarker of aging, but what is homocysteine, and why is it relevant?

Homocysteine is an amino acid produced by the body during the metabolism of methionine, which is an essential amino acid. After its production, homocysteine can be converted back into methionine or irreversibly transformed into cysteine, a precursor to glutathione. Normal homocysteine levels are maintained through the efficient functioning of these metabolic pathways, specifically the balance between remethylation and transsulfuration. As such, homocysteine serves as a marker at the end of this intricate metabolic pathway. Homocysteine levels can be checked through a simple blood test and has widespread clinical applicability. What lies ahead is an overview on how to understand your results, encapsulating the biochemistry at play needed to elucidate the significance of homocysteine levels in relation to your health.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10780827/

 

LEVELS OF HOMOCYSTEINE

 

Optimal Level: 6 to 10 µmol/L

Normal: 6  to 15 µmol/L (micromoles per liter)

Mildly Elevated: 15 to 30 µmol/L

Moderately Elevated: 30 to 100 µmol/L

Severely Elevated: Above 100 µmol/L

 

HOMOCYSTEINE WITH AGE

Young Adults (20-39 years):

Optimal Range: 5 to 10 µmol/L

Middle-Aged Adults (40-59 years):

Optimal Range: 6 to 12 µmol/L

Older Adults (60 years and above):

Optimal Range: 7 to 15 µmol/L

What causes elevations or reductions?

The metabolism of homocysteine relies on various nutrients, particularly folate, vitamin B12, and vitamin B6. This nutritional aspect of homocysteine elevation has some nuance. Importantly, homocysteine levels in the blood must be viewed as a balance between remethylation and transsulfuration—the harmony of which influences plasma homocysteine concentrations. Consequently, elevated levels could indicate an issue with overall methylation, suggesting potential underlying problems such as MTHFR mutations or nutrient deficiencies. 

To illuminate this relationship, folate and vitamin B12 are essential for the remethylation of homocysteine into methionine. On the other hand, vitamin B6 plays a crucial role in the transsulfuration pathway, where a deficiency can lead to a buildup of homocysteine that cannot be converted into cysteine.

B vitamins are not the only nutritional aspect of homocysteine levels. An excess amount of methionine (present in animal foods) with an absence of glycine (found in collagen rich foods) can cause elevated homocysteine. Methionine is an essential amino acid “excessive intake can overwhelm the remethylation pathways, especially if there are insufficient levels of B vitamins”. 

Oxidative stress and homocysteine 

 

Homocysteine levels are also linked to oxidative stress, mechanistically this is expressed in a variety of different ways. Firstly, homocysteine itself can undergo autoxidation (it has a free thiol group) and generate free radicals– increased levels can increase the rates of this autoxidation and thus the damage caused. 

Homocysteine and injuries

 

Extremely relevant to bodybuilders and athletes generally, elevated homocysteine levels seem to adversely affect connective tissue health by disrupting protein synthesis and structural integrity. There is a key enzyme involved in collagen fibers cross linking– called lysyl oxidase (Lox). Elevated homocysteine levels inhibit lox, hindering collagen cross linking. This all happened via inflammatory pathways, specifically involving interleukin 6– having the dual role of upregulating osteoclast activity (bone breakdown) as well as genetically silencing Lox production.

 

My protocol:

 

I have the MTFR mutation so I take 1500 mg of trimethylglycine as well as a methylated b complex every other day. My homocysteine levels are constantly down to low normal, they used to be consistently high normal. I think shooting for low normal is certainly worthwhile in the road of performance optimization.