Monday, January 28, 2013

Homocysteine, Mutations, and Sulfur Sensitivity

By Christian Wernstedt

[Originally published on the VitalObjectives blog]

Homocysteine is a molecule created in the process of what's broadly called "methylation", and is believed to be toxic to the endothelial cells that line blood vessels, and an association has been found between cardiovascular disease (CVD) and homocysteine. Some practitioners and researchers even believe that homocysteine is much more important than LDL cholesterol as a risk factor in CVD.

High homocysteine is associated with an extensively researched genetic variant (or polymorphism) named MTHFR C677T, and which if present can often be effectively addressed by eating more foods that contain natural folates such as green leafy vegetables or egg yolks, or by carefully adding a L-5MTHF supplement. (Not "folic acid"which may be toxic in this situation.)

Given the above, low homocysteine levels are typically lauded as a sign of good health. In fact, as with cholesterol, many clinical laboratories have recklessly (or by government decree?) put 0.0 at the low end of their reference interval for homocysteine.

Being no less flattered than most by such follies, I have been proud of my low homocysteine at 5.8 umol/l , seeing it as a sign of health.


The body detoxifies homocysteine essentially through either recycling the molecule back to methionine (the essential amino acid which it was built from in the first place), or by putting it through a pathway that ultimately converts it into sulfite/sulfate, alpha-ketoglutare, ammonia, and glutathione.

Given these options, if homocysteine is low in the body, it could be for three major reasons:

  1. A high rate of conversion back to methionine. (A good reason in most cases.)
  2. Low production because upstream processes are not working correctly or because a precursor such as methionine doesn't exist in enough quantity. (A bad reason because the ongoing generation and regeneration of homocysteine and methionine from each other drives other crucial processes in the body.)
  3. A high rate of conversion of into sulfite/sulfate etc. (A bad reason if levels of sulfate, alpha-ketoglutarate or ammonia generated this way become toxic - more below.)
Let's look at the pathway in #3 because this is what I have researched when looking into my own issues and biochemistry,

There is an enzyme, CBS, responsible for the first step of conversion through this chain by turning homocysteine into an intermediate called cystathionine. As it happens, the CBS enzyme may be working too fast due to certain rather common variants of genes related to CBS activity. I have several of these variants (e.g., CBS C699T, A360A and BHMT 2,4,8) which make the CBS enzyme work up to ten times faster than normal.

When homocysteine is excessively pulled in this direction by CBS, the following compounds are created at possibly toxic levels:
  • Sulfite and ultimately sulfate - both toxic to the body, but sulfate less so. (When I recently peed on a test strip for sulfate, results came out very high.)
  • Alpha-ketoglutare - high levels can create excess glutamate in the presence of mercury and lead. Glutamate is an excitatory neurotransmitter involved in anxiety, ADHD, and pain sensitivity. (I have mercury fillings, by the way...)
  • Ammonia - high levels act as an irritant and may cause excess cortisol and contribute to the downward spiral of adrenal fatigue and hormone problems that is common in so many (euphemism for "virtually all") people. (Personally, I seem only mildly affected by this as my urinary ammonia is only slightly elevated, and my hormone profile fairly good.)
So what to do? It depends on the person (including which other road blocks are present) and how severe the problems are, but in outline: Reduce sulfur foods and meats (yes, even a vegan diet may be needed in extreme cases), support the detoxification and elimination of ammonia and sulfur. (There are some protocols for this that go far beyond what I have room to discuss here.)

Take away points:
  • One can have low homocysteine and therefore receive a "clean bill of health", yet suffer from mild to severe health issues due to common metabolic pathway problems that result in low homocysteine.
  • If a person has homocysteine, say, below 6 umol/l (some practitioners say 7), it is reasonable to investigate underlying issues. Helpful in that case as a first step would be a 23andMe test, using a sulfate detection strip, or even better a sulfite detection strip (let me know if you know where to find one).

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