Here is my latest article about how the CYP3A4 enzyme metabolises levodopa and controls its bio-availability and haf-life. It is based on a 50-day cycle (n=1) during which CYP3A4 was alternatively non-inhibited and inhibited. The results confirm that CYP3A4 powerfully inhibits levodopa and may be more important in its action than DDC, the enzyme that is inhibited by Carbidopa. An important point concerns the processes and relative speeds of inhibition and regeneration of CYP3A4 which automatically lead to severe fluctuations in enzyme activity when inhibition is stopped or used casually. Daily controlled inhibition of CYP3A4 using grapefruit juice in this trial produced considerable attenuation of Parkinson's disease symptoms without off periods and improved quality of life, probably due to a more regular supply of levodopa to the brain. During CYP3A4 inhibition, levodopa can remain active for 6-8 hours. Inhibition stops or casual consumption of grapefruit juice however lead to worsening of the symptoms, which may be why some people have reported that grapefruit juice does not work for them. Daily, controlled inhibition gave excellent results. CYP3A4 inhibition by polyphenols in healthy and unhealthy diets is also briefly discussed in the light of good dietary practice and trying to relate on and off days to diet history.
This paper contains a great deal of information and ideas for anyone who is taking levodopa in any form. The information in the abstract is very limited compared to the body of the article, so if you are interested, download the whole paper.
By joining up the dots concerning inhibition and regeneration of CYP3A4, I now believe that the action of this enzyme is of major importance for PwP and is the principal cause of the on/off times of PD. Understanding the kinetics of these two processes is critical to learning about how it affects levodopa availability and degradation and how it affects your symptoms.
The information gained here provides a basis for questions that I could not have framed 6 months ago. We don't yet have the answers, but we have more pieces of the puzzle than we had 6 months ago.
AS usual, I won't be answering questions about specific drugs that could be dangerous if used with grapefruit juice. Please ask your doctor about that. The answer to those questions is also in the references at the end of this paper.