Highlights
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- Vitamin D is of crucial importance for brain functioning.
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- Two human trials found significant seizure reduction after supplementation.
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- Vitamin D works on both genomic and non-genomic levels.
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- Some anti-epileptic drugs appear to influence vitamin D levels.
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- Correcting my deficiency was one of the best things I ever did!
I became interested in the influence of nutrients on epilepsy many years ago. I remember reading a rather obscure article about how magnesium might alleviate seizure severity. I was stunned. I always thought that a seizure was an uncontrollable mental hiccup that had gotten gigantically out of hand. Could there be more to it? Could nutrients possibly have a moderating influence?
Why, yes!
Today, let’s look at vitamin D. About 8 years ago, my doctor did some bloodwork on me and found a major vitamin D deficiency. She put me on supplements. Then, I noticed something peculiar. My energy exploded, as I had expected. What I had not expected was that I started to feel a lot more stable in my head. Gone were the pesky moments of disorientation, and even though the number of seizures did not change, I retained consciousness much more often than before. Speaking of health victories.
Vitamin D is a hot topic and appears to play a role in just about every aspect of health. For the brain specifically, vitamin D is crucial. It plays a role in a wide variety of neurological diseases, including epilepsy . Furthermore, vitamin D protects brain cells and facilitates brain development . To cap it all, everywhere in the nervous system specific receptors for vitamin D can be found .
An old discovery revisited
The idea that vitamin D might play a role in reducing the severity of epileptic seizures is not new. Back in 1974, Danish researchers gave patients high doses of vitamin D for 48 days, ranging from 8000-16000IU per day. The effect was significant: an average seizure reduction of 30% . True, they used the synthetic version of vitamin D, vitamin D2, which is no longer recommended today, but the effect was nevertheless remarkable.
There was only one other human trial I could discover, which was conducted a whole 38 years after the Danish trial. 13 deficient patients with drug resistant epilepsy received a one-time dose of 40.000 – 200.000 IU. Speaking of a correction! Then the patients were kept on a maintenance dose of 2000 – 2600 IU. If the high doses make you blink twice, I should mention that no toxicity occurred. The results were positive: 10 patients experienced a median seizure reduction of 40% after supplementation, and 5 patients even experienced a ≥50% reduction in number of seizures .
What else do we know?
Apart from these two human trials, indirect evidence is most suggestive. Newly diagnosed epilepsy patients are frequently found to have significantly lower vitamin D levels than healthy controls, even when controlling for daylight exposure . Existing patients also commonly exhibit vitamin D deficiencies .
Studies in mice also show promising results. When mice are given a chemical that triggers seizures together with vitamin D, seizures take longer to develop, are of shorter duration, and the poor mice die off less frequently than without the addition of vitamin D. The effect, however, was short-term. If the vitamin D was given more than 3 hours before the seizure-triggering chemical, the positive effect disappeared . Furthermore, partially knocking out the vitamin D receptor gene in mice results in a significant increase in seizure severity, implying that vitamin D metabolism has a direct modulating role in the development of epilepsy .
I would be amiss if I did not mention genetic evidence. Exciting new studies suggests that genetic variations of the vitamin D receptor appear to play a role in genetic susceptibility to epilepsy. A certain genetic variation of the vitamin D receptor is found significantly more often in epilepsy patients, and another group of closely related genetic receptor variants significantly increased the risk of developing temporal lobe epilepsy .
A potential mechanism
Lovers of detail, rejoice! Vitamin D probably exerts both genomic and non-genomic effects . First of all, the genomic effects. Vitamin D can directly regulate gene expression. One mechanism is that it downregulates the production of certain inflammatory cytokines (IL-1β and TNF-α) which increase the risk of seizures. IL-1β sends more calcium into the neurons, increasing the probability that the excitatory neurotransmitter glutamate will be released. IL-1β also inhibits glutamate reuptake and reduces activity of the inhibitory neurotransmitter GABA. The other cytokine, TNF-α, reduces the activity of GABA-A receptors, which results in further reduction of inhibitory signaling. Vitamin D also increases the production of the anticonvulsant growth factors GDNF and NT3 .
The non-genomic effects are less clear, but they likely have something to do with the fine regulation of calcium and chloride currents across neuronal membranes .
A note on AEDs and vitamin D
In patients taking anti-epileptic drugs, researchers found the highest levels of deficiency in patients taking the class of drugs called enzyme inducers, which are older drugs like carbamazepine, phenytoin and phenobarbital . 54% of patients taking inducers had vitamin D deficiency, as opposed to 37% of patients taking non-inducers, such as lamotrigine, valproic acid, gabapentin and levetiracetam. Enzyme inducers have the potential to decrease circulating levels of active vitamin D. I’m oversimplifying here, but you could say that they activate a family of enzymes that are involved in the breakdown of active vitamin D. Extra activation of these enzymes thus causes vitamin D to be broken down faster . In fact, carbamazepine has been associated with lower levels of vitamin D , and some researchers argue that the known undesirable effects of enzyme inducers are highly underappreciated .
Mind you, these are correlations, not causations. Don’t throw your medicines out of the window. But asking your doctor to check your vitamin D levels is probably a good idea.
My final verdict?
For me, supplementing with vitamin D made a world of a difference, and it is here to stay. And I found through self-experimentation that I need quite a high daily dose to maintain the stabilizing effects. I read somewhere (unfortunately I can’t remember where) that epileptics should take between 5.000 – 7.000 IU per day. That was my starting point. From there, I increased the dose bit by bit, and I found that I function best at 12.000 IU per day. To put that into perspective, the most frequently seen recommended daily intake is about 600 IU for adults. That’s a huge difference. Yes, my blood levels are high, but there is no toxicity. And my brain is whirring along a lot more smoothly.
I’m sharing what works for me. This is not a recommendation. Tread with caution when experimenting with high doses, for one study found that taking a dose of 10.000 IU significantly decreased bone mineral density . However, the effect appears to be mitigated by vitamin K2, which you should always take in conjunction with vitamin D . Vitamin D helps to absorb calcium, but it needs vitamin K2 to actually put it into the bones.
What about you? Do you have experiences with vitamin D? What was it like? I’d love to hear some comments from you!