Serine may increase the bioavailability of levodopa by 22%
 

First my thanks go to pdinva on HU for pointing me to this paper [1].

Probably most of the PwP on this forum rely on levodopa based drugs, such as Sinemet and Stalevo, to have a reasonable quality of life. It is important, therefore, that large amounts of each dose gets through to the brain. Even more important is that the absorbtion is consistent from dose to dose.

In the early days post diagnosis, you are probably producing enough dopamine yourself (endogenous) and have enough dopamine reservoirs in the surviving dopaminergic neurons to not be affected much by any variability of absorbtion.

Unfortunately as time goes by this changes: gastric emptying slows, protein competition becomes more important. This manifests itself by more "off" time, even lost doses, and declining performance in the afternoon. And, if the PwP takes more levodopa to account for the low bioavailability, when things go well and an unexpected high amount of levodopa is absorbed, this can lead to more levodopa induced dyskinesia.

Guebila and Thiele built a mathematical model that predicted:

" ... an improvement in bioavailability, as reflected by blood concentrations of levodopa with protein redistribution diet by 34% compared with a low-protein diet and by 11% compared with the a.c [before food] administration. These results are consistent with the reported better outcome in late-stage patients. A systematic analysis of the effect of different amino acids in the diet suggested that a serine-rich diet could improve the bioavailability by 22% compared with the a.c. administration."

This possible effect of serine is new to me.

Reference:

[1] "Model-based dietary optimization for late-stage, levodopa-treated, Parkinson’s disease patients"
Marouen Ben Guebila and Ines Thiele
npj Systems Biology and Applications (2016)
https://www.nature.com/articles/npjsba201613.pdf

John

this paper on soybeans increasing ON time was referenced
 

Effects of soybean ingestion on pharmacokinetics of levodopa and motor symptoms of Parkinson's disease--In relation to the effects of Mucuna pruriens. - PubMed - NCBI


J Neurol Sci. 2016 Feb 15;361:229-34. doi: 10.1016/j.jns.2016.01.005. Epub 2016 Jan 6.
Effects of soybean ingestion on pharmacokinetics of levodopa and motor symptoms of Parkinson's disease--In relation to the effects of Mucuna pruriens.
Nagashima Y1, Kondo T2, Sakata M3, Koh J3, Ito H3.
Author information

1
Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-shi, Wakayama 641-8509, Japan. Electronic address: y_naga@wakayama-med.ac.jp.
2
Hana-no-Ie Hospital, 1218-1 Minamiakatsuka, Nogimachi, Shimotsuka-gun, Tochigi 329-0112, Japan.
3
Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-shi, Wakayama 641-8509, Japan.

Abstract

Mucuna pruriens is a levodopa-containing legume and its favorable effects on motor complications in Parkinson disease patients have been reported. The aim of this study was to investigate the effects of another legume, soybeans, on the pharmacokinetics and metabolism of levodopa. Seven parkinsonian patients with the wearing-off phenomenon and dyskinesia and five healthy volunteers participated in this study. We conducted a crossover study of the clinical effects on the participants before and after taking either levodopa (100mg)/carbidopa (10mg) only (LD/CD) or levodopa/carbidopa with 11 g of ground soybeans (LD/CD/soy). Parkinsonism and dyskinesia before and after ingestion of these substances were evaluated using UPDRS part III, the modified Abnormal Involuntary Movement Scale (mAIMS) and a self-rating scale. The concentrations of plasma levodopa and its major metabolites were measured by high-performance liquid chromatography. Clinical assessment and blood sampling were conducted before and three hours after the ingestion of ground soybeans. When the patients took LD/CD/soy, they had a significantly longer on-period (p=0.028) and a lower mAIMS score (p<0.001). From the comparison of the results of pharmacokinetic study before and after taking LD/CD or LD/CD/soy, the estimated marginal mean (EMM) of HVA after LD/CD/soy increased in the PD group. EMMs of 3-OMD after LD/CD/soy significantly decreased both in PD patients and healthy controls. These results indicate that soy partly increased the bioavailability of levodopa and suppressed levodopa degradation through COMT. Soybeans may have favorable effects on the motor complications occurring under current levodopa therapy. Further investigation to clarify the mechanism underlying such effects is required.

Thanks for the reference Soccertese. It looks like soybean is a COMT inhibitor.

Entacapone is another COMT inhibitor. Stalevo = L/C/E.

John

going to try some TOFU

Be careful when playing with soybean.

According to [1]:

"soy isoflavones have been found to inhibit CYP3A4 metabolism"

At least to me, the meaning of this is unclear: "inhibit CYP3A4 metabolism" could mean slowing the destruction of CYP3A4 itself, or it could mean slowing the speed of the the metabolism caused by CYP3A4. I've followed some of the papers cited in [1] and I think that the second meaning is correct. So, in that case soybean is a CYP3A4 inhibitor.

Similar to grapefruit juice, this has the advantage of increasing the AUC of levodopa, which is good. But, it can also lead to increasing the effect of other drugs (e.g. statins), which can result in an overdose.

Reference:

[1] "Interactions between CYP3A4 and Dietary Polyphenols
Loai Basheer and Zohar Kerem"
Oxid Med Cell Longev, 2015
Interactions between CYP3A4 and Dietary Polyphenols

John

noticed this in the article
"We found that threonine, serine, and asparagine resulted in the highest brain bioavailability of levodopa (Figure 5). To our knowledge, these amino acids have not been reported to compete with levodopa in the small intestine and in the brain. Moreover, the amino acids were predicted to compete with levodopa for elimination in the kidneys and trans-stimulate levodopa secretion from the intestinal lumen. It has been shown that serine improves dopamine production.25 Consequently, we ranked serine as the amino acid with the highest contribution to levodopa bioavailability."