Ginkgo
(Ginkgo biloba) is herbal product that is extracted from the leaves and seeds
of its tree, which is indigenous to China, Japan, and Korea, but also found in
Europe and the US.1 It is most known for its use to improve memory and
for the treatment of Alzheimer's related dementia.1 However, it has many
other claimed benefits for other medical conditions as well. Once the
harvested leaves have been dried, they are then pressed into balls where they
are put through extraction methods with acetone/water and then undergo a number
of purification procedures.
The
most common active compounds found in ginkgo extract include flavonoids,
bioflavonoids, proanthocyanidins, and trilactonic diterpenes (ginkgolide A, B,
C). Unfortunately, depending on the part of the plants used and the
method used for extraction, there is chance that the extract can contain a
substance known as ginkgotoxin, which also has the names 4'-O-methylpyridoxine
or "B6 antivitamin".2-5 Unfortunately, overconsumption of
sources or supplements containing this compound has resulted in seizures and
possible death.2
The
increase risk for developing seizures comes from an imbalance in the amount of
glutamate compared to GABA (see the figure provided).5 This adverse
effect appears to occur from a competition with vitamin B6 (pyridoxine) for
binding to pyridoxal kinase, an enzyme needed in the formation of pyridoxal
pyrophosphate. Interestingly, vitamin B6 and ginkgotoxin are structurally
very similar, but it appears that ginkgotoxin has a stronger binding affinity
for pyridoxal kinase than vitamin B6, as suggested by its lower Km. As a
result of the reduction in pyridoxal pyrophosphate, there is less formation of
the major inhibitory neurotransmitter, g-aminobutyric acid (GABA).5
This causes the neuron to be in a state that is more likely to achieve its
threshold for another nerve impulse (or action potential). Furthermore,
the increased concentration of glutamate worsens the risk because of its
ability to lower the seizure threshold. Together this environment is
ideal for increased and possible, erratic nerve impulses that can result in a
seizure.
It is unknown how much ginkgotoxin containing
substances needs to be consumed and over what period of time before a seizure
will occur for any patient. It is likely that not only the dose of
ginkgotoxin and time of consumption play an important role in this risk, but
the patient's baseline risk for seizures, use of concomitant medications also
known to lower the seizure threshold, and the nutritional status of the patient,
especially as it relates to vitamin B6. While many name brand supplements
probably do not contain ginkgotoxin, their lack of accountability for the
manufacturing process by the Food and Drug Administration offers no guarantees.
References:
- National Institutes of Health. National Center for Complementary and
Alternative Medicine. Ginkgo. NCCAM Publicaton No. D290. July 2010.
- Wada K, Ishigaki S, Ueda K et al. An antivitamin B6,
4'-methoxypyridoxine, from the seed of Ginkgo biloba L. Chem Pharm
Bull 1985;33:3555-7.
- Arenz A, Klein M, Fiehe K et al. Occurrence of neurotoxic
4'-O-methylpyridoxine in Ginkgo biloba leaves, Ginkgo medications and
Japanese Ginkgo food. Planta Med 1996;62:548-51.
- Van Beek TA, Montoro P. Chemical analysis and quality control of
Ginkgo biloba leaves, extracts, and phytopharmaceuticals. J Chromatogr
A 2009;1216:2002-32.
- Kastner U, Hallmen C, Wiese M et al. The human pyridoxal kinase, a
plausible target for ginkgotoxin from Ginkgo biloba. FEBS J
2007;274:1036-45.
