As my brain fog continues to be my worst symptom, I was thinking Ginkgo Biloba, rumoured to help brain circulation, might be worth a try. Did a bit of research and while I came up with many positive reviews, this post from some CFS forum makes it sound like it's possibly a bad idea.
Ginkgotoxin is structurally related to Vit.B6 and likely interferes with its biosynthesis, metabolism or function.
Vitamin B6: A Long Known Compound of Surprising Complexity
http://www.mdpi.com/1420-3049/14/1/329/pdf
The Diversity of Vit B6 Derivatives
Quote: As described in the preceding paragraphs, vitB6 is a well-investigated compound critical for many cellular processes as either a central cofactor or as a potent antioxidant. However, it is noteworthy that a variety of different PN, PM, and PL derivatives have been described, for which the precise function is not understood (Table 2). These derivatives potentially have novel functions, and may be crucial to fully appreciate the biological relevance of vitB6. The best known of these derivatives is probably 4-O-methylpyridoxine or ginkgotoxin from the tree Ginkgo biloba [12, 97]. The compound has been found in different tissues with the highest concentrations being present in seeds [98]. Although it has been shown that the additional 4'-O-methyl group most likely derives from methionine, and that both phosphorylated and non-phosphorylated forms of pyridoxine are methylated, the biosynthetic pathway leading to 4-O-methylpyridoxine is still unresolved [98, 99]. Ingestion of the toxin can lead to Gin-nan-sitotoxism, epileptic convulsions, and other neuronal disorders [100]. As seeds from Ginkgo trees are a food source in China and Japan, and extracts from leaves are used in pharmaceutical products, they represent a potential health risk. The PLP-dependent enzyme glutamate decarboxylase (GAD), which is critical for synthesis of the neurotransmitter GABA was discussed as a potential target of 4-O-methylpyridoxine. However, there is no clear evidence that ginkgotoxin significantly reduces GAD activity when present in physiologically relevant concentrations [101]. In contrast, recent work rather suggests that the toxin is competing with PN/PM/PL for human pyridoxine kinase [97]. This in turn might reduce the pool of available PLP and PMP in the brain and negatively affect GAD activity and GABA biosynthesis [97].
The human pyridoxal kinase, a plausible target for ginkgotoxin from Ginkgo biloba
http://www3.interscience.wiley.com/cgi- ... 1&SRETRY=0
Quote: Ginkgotoxin (4?-O-methylpyridoxine) occurring in the seeds and leaves of Ginkgo biloba, is an antivitamin structurally related to vitamin B6. Ingestion of ginkgotoxin triggers epileptic convulsions and other neuronal symptoms. Here we report on studies on the impact of B6 antivitamins including ginkgotoxin on recombinant homogeneous human pyridoxal kinase (EC 2.7.1.35). It is shown that ginkgotoxin serves as an alternate substrate for this enzyme with a lower Km value than pyridoxal, pyridoxamine or pyridoxine. Thus, the presence of ginkgotoxin leads to temporarily reduced pyridoxal phosphate formation in vitro and possibly also in vivo. Our observations are discussed in light of Ginkgo medications used as nootropics.
Quote: Ginkgotoxin is structurally related to vitamin B6 and likely interferes with its biosynthesis, metabolism or function. It is for this reason that ginkgotoxin is considered to be a B6 antivitamin, as is 4?-deoxypyridoxine (DPN) [5] (Fig. 1), a synthetic analogue of the B6 vitamers pyridoxal (PL), pyridoxamine (PM) and pyridoxine (PN). The physiologically active B6 vitamers pyridoxal phosphate (PLP) and pyridoxamine phosphate (PMP) are most important, because they participate in many enzymatic reactions including amino acid metabolism [6] and reactions involved in the synthesis of neurotransmitters (e.g. dopamine, serotonin, norephedrine and c-aminobutyric acid) [7].
Quote: To date, the effect of ginkgotoxin on pyridoxal kinase had been studied only with a partially purified homogenate from mouse brain [5]. Detailed experiments on the mode of inhibition of the human enzyme by ginkgotoxin are lacking. This study shows for the first time an enzymatic conversion of ginkgotoxin to ginkgotoxin phosphate and of DPN to DPNP by homogeneous human pyridoxal kinase.
Quote: It should be emphasized that the toxin has been reported to also be present in different Ginkgo remedies [2,3], which are top-selling phytotherapeutic medications in Europe [22]. Strikingly, two cases of recurrence of well-controlled epilepsy after ingestion of Ginkgo biloba remedies by two elderly patients have been reported recently [23]. After the immediate withdrawal of the Ginkgo remedy, in both cases no further epileptic convulsions were stated within the observation interval (8 months, first patient, 4 months, second patient). According to another publication, several other cases of seizure associated with Ginkgo have been reported [24]. The authors of these case studies assume that the occurrence of the epileptic convulsions was due to the ingestion of Ginkgo remedies. However, they neither specify the respective remedies, nor do they mention their composition.
I guess perhaps you should be critical of OTC supplements which contain Ginkgo biloba -- especially when you are already deficint in P-5-P?
Any validity?
Ginkgotoxin is structurally related to Vit.B6 and likely interferes with its biosynthesis, metabolism or function.
Vitamin B6: A Long Known Compound of Surprising Complexity
http://www.mdpi.com/1420-3049/14/1/329/pdf
The Diversity of Vit B6 Derivatives
Quote: As described in the preceding paragraphs, vitB6 is a well-investigated compound critical for many cellular processes as either a central cofactor or as a potent antioxidant. However, it is noteworthy that a variety of different PN, PM, and PL derivatives have been described, for which the precise function is not understood (Table 2). These derivatives potentially have novel functions, and may be crucial to fully appreciate the biological relevance of vitB6. The best known of these derivatives is probably 4-O-methylpyridoxine or ginkgotoxin from the tree Ginkgo biloba [12, 97]. The compound has been found in different tissues with the highest concentrations being present in seeds [98]. Although it has been shown that the additional 4'-O-methyl group most likely derives from methionine, and that both phosphorylated and non-phosphorylated forms of pyridoxine are methylated, the biosynthetic pathway leading to 4-O-methylpyridoxine is still unresolved [98, 99]. Ingestion of the toxin can lead to Gin-nan-sitotoxism, epileptic convulsions, and other neuronal disorders [100]. As seeds from Ginkgo trees are a food source in China and Japan, and extracts from leaves are used in pharmaceutical products, they represent a potential health risk. The PLP-dependent enzyme glutamate decarboxylase (GAD), which is critical for synthesis of the neurotransmitter GABA was discussed as a potential target of 4-O-methylpyridoxine. However, there is no clear evidence that ginkgotoxin significantly reduces GAD activity when present in physiologically relevant concentrations [101]. In contrast, recent work rather suggests that the toxin is competing with PN/PM/PL for human pyridoxine kinase [97]. This in turn might reduce the pool of available PLP and PMP in the brain and negatively affect GAD activity and GABA biosynthesis [97].
The human pyridoxal kinase, a plausible target for ginkgotoxin from Ginkgo biloba
http://www3.interscience.wiley.com/cgi- ... 1&SRETRY=0
Quote: Ginkgotoxin (4?-O-methylpyridoxine) occurring in the seeds and leaves of Ginkgo biloba, is an antivitamin structurally related to vitamin B6. Ingestion of ginkgotoxin triggers epileptic convulsions and other neuronal symptoms. Here we report on studies on the impact of B6 antivitamins including ginkgotoxin on recombinant homogeneous human pyridoxal kinase (EC 2.7.1.35). It is shown that ginkgotoxin serves as an alternate substrate for this enzyme with a lower Km value than pyridoxal, pyridoxamine or pyridoxine. Thus, the presence of ginkgotoxin leads to temporarily reduced pyridoxal phosphate formation in vitro and possibly also in vivo. Our observations are discussed in light of Ginkgo medications used as nootropics.
Quote: Ginkgotoxin is structurally related to vitamin B6 and likely interferes with its biosynthesis, metabolism or function. It is for this reason that ginkgotoxin is considered to be a B6 antivitamin, as is 4?-deoxypyridoxine (DPN) [5] (Fig. 1), a synthetic analogue of the B6 vitamers pyridoxal (PL), pyridoxamine (PM) and pyridoxine (PN). The physiologically active B6 vitamers pyridoxal phosphate (PLP) and pyridoxamine phosphate (PMP) are most important, because they participate in many enzymatic reactions including amino acid metabolism [6] and reactions involved in the synthesis of neurotransmitters (e.g. dopamine, serotonin, norephedrine and c-aminobutyric acid) [7].
Quote: To date, the effect of ginkgotoxin on pyridoxal kinase had been studied only with a partially purified homogenate from mouse brain [5]. Detailed experiments on the mode of inhibition of the human enzyme by ginkgotoxin are lacking. This study shows for the first time an enzymatic conversion of ginkgotoxin to ginkgotoxin phosphate and of DPN to DPNP by homogeneous human pyridoxal kinase.
Quote: It should be emphasized that the toxin has been reported to also be present in different Ginkgo remedies [2,3], which are top-selling phytotherapeutic medications in Europe [22]. Strikingly, two cases of recurrence of well-controlled epilepsy after ingestion of Ginkgo biloba remedies by two elderly patients have been reported recently [23]. After the immediate withdrawal of the Ginkgo remedy, in both cases no further epileptic convulsions were stated within the observation interval (8 months, first patient, 4 months, second patient). According to another publication, several other cases of seizure associated with Ginkgo have been reported [24]. The authors of these case studies assume that the occurrence of the epileptic convulsions was due to the ingestion of Ginkgo remedies. However, they neither specify the respective remedies, nor do they mention their composition.
I guess perhaps you should be critical of OTC supplements which contain Ginkgo biloba -- especially when you are already deficint in P-5-P?
Any validity?