What is The Optimal Level of Homocysteine?

MTHFR and homocysteine are linked because homocysteine builds up when the folate cycle isn't working efficiently, which can happen with MTHFR. Because of this, testing homocysteine can be a helpful way to determine whether the health changes you are making for your MTHFR gene mutation are actually effective for you. In this post, we will cover Homocysteine testing and parameters - what is normal, what isn't, and what is considered normal but maybe shouldn't be.

Testing Homocysteine

Homocysteine tests are simple blood tests that can be ordered by your doctor. The blood must be drawn when you are fasting for accurate results. Scheduling your blood draw first thing in the morning, before you have eaten or had coffee, is the best strategy. Any protein you eat before your test can skew the numbers because methionine in your food may cause a temporary rise in homocysteine. The best way to ensure a blood test is fasting is to schedule your blood test early in the day, before you have eaten anything. Eight to twelve hours of fasting (like you would get overnight) is best for the most accurate results.

"Normal" Level vs. Optimal Level of Homocysteine

The current medical standard in the U.S. considers a normal range for homocysteine to be 5-15 µmol/L (micromoles/Litre). Anything above 15 micromols/L is considered high and is called hyperhomocysteinemia. There is a growing body of evidence that the normal level should be adjusted:

• A study published in the New England Journal of Medicine shows that the risk of carotid artery thickening and stenosis begins to increase for men at 9.2 umol/L (although the risk for women seems to remain stable until 11.4 umol/L). Both of these are significantly lower than the 15 umol/L that is considered normal. Risk increases at 9.2 umol/L

• A meta-analysis published in the Journal of the American Medical Association shows that a 3 umol/L decrease in homocysteine leads to an 11% lower risk of ischemic heart disease and a 19% lower risk of stroke.

• A strong linear relationship exists between homocysteine levels and death in patients with coronary disease. The lowest-risk group has homocysteine below 9 umol/L, and risk increases from there, both within and outside the normal range.

  • Homocysteine <9 umol/L = 3.4% risk of death

  • Homocysteine 9 umol/L - 14.9 umol/L = 8.6% risk of death

  • Homocysteine >15 umol/L = 24.7% risk of death.

  • Risk increases at 9 umol/L

• In a study using homocysteine levels as a predictive marker for negative outcomes with Covid-19, an increased risk for pathological lung changes on CT was shown at 8 umpl/L Risk increases at 10.58 umol/L

  
  

If The "Normal" Levels aren't Ideal, What Is?

All of the risks for negative health outcomes seem to be lowest around the 6 - 8 umol/L mark, and according to the research cited above, risks begin to increase between 8 and 9 umol/L. While the medically "normal" range will stay the same, I would like to propose 6 - 8 umol/L as the optimal level of homocystein. This is an estimate based on the research discussed above. Joe Pizzorno, a legend in the natural wellness community, estimates the ideal range to be 5.0 to 7.0. Ben Lynch, the epigenetic expert, estimates the ideal to be between 6 and 9 umol/L.

If Homocysteine Is So Bad, Why Aren't We Aiming for Zero?

Too much homocysteine is bad for sure, and with MTHFR and homocysteine, that is the direction we usually trend, but remember that homocysteine is absolutely essential. If your homocysteine is too low (hypohomocysteinemia), then there are also health consequences.

Without homocysteine you can't make glutathione, which is one of your main defenses against oxidative stress. Without glutathione, your health would go sideways pretty quickly.

Homocysteine is also the precursor for something called alpha-ketobutyrate, which is a vital ingredient in the process that makes cellular energy. Very few studies are done about low homocysteine levels (I mean VERY few. I can count them on two hands). By far the most interesting one shows a link between low homocysteine and peripheral neuropathy. It states that fully 41% of people with low homocysteine have peripheral neuropathy, which is hugely significant.

In my opinion, this implies that the lack of glutathione and consequent difficulty with free radicals is leading to higher levels of inflammation and nerve damage. Joe Pizzorno put forward a similar theory here.

I wouldn't be surprised to see a link between low homocysteine and chronic fatigue, as well, although the research has not yet been done.

The bottom line is that we need homocysteine, but too much of it becomes a big problem. Aim for 6 - 8ish micro mols/L.

References:

• Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A, Allen RH. Total homocysteine in plasma or serum: methods and clinical applications. Clinical Chemistry. 1993 Sep;39(9):1764-79. .

• Selhub J, Jacques PF, Bostom AG, D'Agostino RB, Wilson PW, Belanger AJ, O'Leary DH, Wolf PA, Schaefer EJ, Rosenberg IH. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. New England Journal of Medicine. 1995 Feb 2;332(5):286-91.

• Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. Journal of the American Medical Association. 2002 Oct 23-30;288(16):2015-22.

  
  

• Shawkat Ahmed H, Noori SH. The Importance of Serum Homocysteine as a Biomarker in Diabetic and Obese COVID-19 Patients. Cellular and Molecular Biology (Noisy-le-grand). 2023 Feb 28;69(2):52-59.