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Ginkgo Biloba interferes with B6? Rich?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Rockt, Sep 3, 2011.

  1. Rockt

    Rockt Senior Member

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    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?
     
  2. richvank

    richvank Senior Member

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    Hi, Rockt.

    It's true that ginkgo biloba contains the toxin mentioned, and it does compete in vitamin B6 metabolism. Whether or not it causes a problem probably depends on the amount. Apparently in Japan some people eat foods made from ginkgo. No doubt they receive a lot more of this toxin than people who take ginkgo as a supplement. There's a basic principle in toxicology that everything is toxic at high enough dose, and "the poison is in the dose." I'm guessing that if this was a major issue, the FDA would have pulled ginkgo off the market, since they tend to be very aggressive against supplements in general.

    Maybe you could consider nattokinase or lumbrokinase. These tend to improve blood circulation, too, and I haven't heard of any toxins in them.

    Best regards,

    Rich
     
  3. Rockt

    Rockt Senior Member

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    Thanks Rich.

    I think I'll try the ginkgo, but not go beyond recommended dosage.

    I tried nattokinase and got tremendous pain in my fingers - like a spontaneous arthritis or something. It scared me and I stopped taking it and the pain stopped immediately. Strange, eh?
     
  4. richvank

    richvank Senior Member

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    Hi, Rockt.

    I hadn't heard of that before. Sounds as though stopping was a good idea!

    Rich
     
  5. SJB944

    SJB944 Senior Member

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    Dr Myhill suggests coconut oil for brain fog. Apparently has good results from some of her patients.
     
  6. Rockt

    Rockt Senior Member

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    Yeah, I was hoping CO would help, but I've been taking it for over a year and no help. I think it's a good part of the low carb diet, though and I like the taste.
     

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