Dosage calculations of CBD, DHA and MCT for Optimal Anticonvulsant Properties.

Found an interesting article about the benefits of caprylic acid found in MCT oil I am supplementing L. I want to do some calculations to see if I am giving the right dose for optimal anticonvulsant effect found in this study.

Optimal anticonvulsant range was found to be 10-30 mmol/kg which showed reduced myoclonic and clonic but not tonic convulsions.  Higher doses seem to not be good. 10-60 mmol/kg actually impaired motor performance and lower doses showed little anticonvulsant effect.  So, I want to make sure I am not over or under doing it with this stuff for L.

If I were to give 10 mmol/kg (trying to stay at a conservative range) for L this is the calculation:

Caprylic acid molar mass = 144.21 g/mol

(144.21g/mol)(10mmol)(mol/1000mmol) = 1.4g in 10 mmol of caprylic acid:

This states that 1.4g is equivalent to 10mmol.

There is 7.6g/15ml of pure MCT oil per the bottle.

Therefore,

7.6g/15ml = (x)/1.4g;

x=0.71ml    This means there is 1.4g of caprylic acid in 0.71ml of the MCT oil.

Now, I need to calculate how many mls I need to give for his weight in kg.

Luki weighs 15.42kg.

0.71ml (x) 15.42 kg = 10.9 ml or approximately 11 ml (or little less than one tablespoon) of MCT must be given daily for optimal anticonvulsant effect.  

I am currently  only giving him approximately 4 ml per day so I can definitely double the dose but right now his seizures are well controlled.   I don't have access to the full article so I don't know how long the study lasted and the duration the caprylic acid was given.

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 how much DHA I am actually giving L .

Molar mass of DHA: 328.488 g/mol

I administered 1.6g of DHA per day.

(mol/328.488g)(1.6g)= 0.00487mol(x)1000 = 4.87mmol total administered per day.

4.87mmol/15.42kg = 0.32mmol/kg

Wow, didn't realize I am giving him so little yet it makes such a huge and drastic difference!

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 how much I am giving L of CBD:

CBD molecular weight is 314.4617g/mol

I am currently giving him 16 mg divided into two doses as recommended by the pediatric dosage guidelines from theroc.org. Click here for details.

(mol/314.4617g)(16mg)(1g/1000mg)=0.00000508mol or 0.05mmol/15.42kg=3.3x10(3) mmol/kg

That is very little compared to the caprylic acid! Hmm.maybe I can administer a little more of this stuff..

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how much resverotrol I should be giving for the kind of seizure control found in this study:

The bottle of reseverotrol I purchased states there is 130mg/5ml.

I usually give about 3ml twice a day for a total of 6 ml per day..

 (130mg/5ml)(6ml) = 156mg per day is what I am giving now.  

The paper states 40mg/kg was administered for seizure control.

So, according to the paper, I should be administering (40mg/kg)(15.42kg)=616.8 mg!

(616.8mg)(5ml/130mg)= 24ml per day or 12 ml twice a day is what I should be giving him! That's a lot!

There is only 148ml in the bottle and this stuff is not cheap!  148ml/24ml =6.  A bottle will only last me 6 days!!

****The study involved a one time administration of  resverotrol before seizures were induced.  They don't offer any recommendations for a daily maintenance dose which is too bad.    But, at least it lets me know how much resverotrol I should give should he have a seizure.   

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I would like to add to the regimen some curcumin.  Here is an article that addresses the protective effect of curcumin against seizures and cognitive impairment in seizure induced rats.  They found that an optimal dose of 300mg/kg given for 30 days "significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure score and decreased the number of myoclonic jerks".  They also found reversal of cognitive impairment and oxidative stress when pretreated with curcumin before seizures were induced.


(300mg/kg)(15.42kg) =   4,626 mg for L per day.


I really like this brand of curcumin.

There is 750 mg per capsule.

4626mg/750 mg = 6 capsules per day or 3capsules, bid.


**This study only used curcumin as a source of anticonvulsant but since I am adding others (CBD, MCT, DHA and resveratrol), I am wondering if I can use a little less than this amount...

How I stopped L's seizures with DHA.

Disclaimer:  This blog post is an account of how DHA has helped in stopping seizures for my own son.  It is in no way an instruction for treating seizures in anyone else.  I do not receive any reimbursement for promoting any of the products mentioned below.  



"Seizures involve a complex array of factors, so I don't wish to offer fatty acids as a simple solution.  Indeed, we don't really know much at all about fatty acids and seizures. Yet our growing knowledge of the importance of fatty acids in the brain may lead to some important breakthroughs in helping people with seizure disorders."

 -Michael A. Schmidt, PhD author of Brain-Building Nutrition

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A couple of weeks ago, our little family went on a short summer trip to Bishop and Mammoth. We tagged along Gabriel who was assigned to audit the power dams at one of the lakes near Bishop and although it wasn't officially a family vacation, Lucas and I had a great time during the day while daddy worked. In the evening, all three of us enjoyed local cuisines for dinner once Gabe returned to the hotel after work. Surprisingly, our favorite restaurant was the one inside a local bowling alley that had great reviews! Nothing fancy, but the service and food was great.     

On the second morning, I was late in administering L's keppra.  Usually, he gets a teaspoonful (500 mg) as soon as he wakes up around 7:00 am but on that particular day, he didn't wake up until 9:00 am.  Five minutes after receiving his keppra, he had the most severe seizure he has ever had.  It was a full tonic clonic with jerking of his whole body and foaming in the mouth.  It lasted for about a minute but felt like an eternity and I was a total wreck.  When we got home a few days later, I ordered an emergency dose of diastat, just in case.  

This is one of his typical seizures. 

I was upset that the keppra was not working and we have had to increase his dose 3 times and yet the seizures were an almost daily occurrence. I almost felt guilty that I was administering something that wasn't fixing the problem but may be contributing to some bad side effects! The seizures would stop for a few days after the increase in dosage then return.  The Charlotte's Web we have been supplementing along with keppra for the past 5 months didn't seem to be making any difference at all.  I am not sure what prompted me, perhaps out of desperation, but I decided to restart the DHA I had been giving L a couple of years back.  I had stopped giving it to him because I didn't think it was having any effect. In hindsight, I realize L never had seizures when he was on DHA the first time at about the age of 18 months.  About a year after I stopped giving him the high dose of DHA, as recommended by Dr. Ron Myers, is when he started with the complex partials.  I doubled the dose this time from 800 mg to 1600 mg a day as he has roughly doubled in weight. The brand I use is Neuromins from Source Naturals which is pure DHA from algae with no EPA or other essential fatty acids. click for link to neuromins    This is what Dr. Myers recommended when I consulted him a few years back.  My calculation of the dosage came out be:
  
We found out L weighs 34 lbs on our last neuro appointment.
 His current weight: (1kg/2.2046lbs) (34 lbs) = 15.42 kg
 1600 mg/15.42kg = 104.76 mg/kg of body weight. 
I give him two doses, once in the morning and once at night.
 104.76 mg/kg divided by twice a day is 51.88 mg/kg per serving. 

We have been seizure free since two days after starting DHA!  That's 11 days straight with no seizures for the first time in 5 months!!!

This log goes back to March 2 with similar entries of almost daily seizure activity.

I continued with the keppra for a few more days but then decided to titrate it down to see what happens.  We are currently at 300 mg in the morning and 400 mg at night.  That is a 30% and 20% reduction, respectively, and still no sign of seizures, yet!!!  I am hoping to slowly titrate down some more but not completely. 

Source Naturals sells various concentrations of neuromins. I purchased the highest concentration which is 200 mg per capsule.  This equates to 4 capsules in the morning and 4 capsules at night.  There are 120 capsules per bottle which means a bottle will last me 15 days.  Amazon sells it for $44.49 per bottle which equates to 0.35 cents per capsule.  At 8 capsules a day, that's $2.80 per day or about $84.00 per month.  The downside is that it can get very expensive and none of this is covered by insurance, of course.  Although, I did mention all this to our neurologist who said Kaiser may supply their own brand of fish oil but will not cover the neuromins. I am hesitant to try other formulations with EFAs that may not be beneficial.  Why mess with a good thing we have right now?  

My method of administering the oil is to break the capsules onto a chinese soup spoon (really useful for squeezing as much oil out of the capsule, I squeeze against the handle) and draw it up in a syringe.  It comes out to be approximately 2.5 ml.  And for good measure, I add 2 ml of coconut oil for the MCT onto another syringe, L hates the taste of coconut oil the most and he won't take too much at once.  I have had to change over to vanilla flavored pure MCT oil I found at Whole Foods which he likes much better.  Then, I chase it all down with Charlotte's Web oil which L likes for its mint chocolate flavor.  And, before he goes to sleep, we give him 400 mg of keppra along with his atropine eye drops.  We are looking for a good source of resverotrol to add to the regimen to "help protect against rancid fats (peroxidized lipids) in the body" (Michael Schmidt, PhD) whenever fatty acid supplements are used.  Who knows what havoc build up of free radicals can cause!  Beta oxidation of  polyunsaturated fatty acids naturally yields free radical ions and although endogenous enzymes like superoxide dismutase act as free radical scavengers, it may not be enough to neutralize all free radicals when supplementing massive amounts of fats and lipids.  



I can't say DHA is the sole factor that has stopped his seizures which is why I won't stop keppra completely.  Perhaps, it is the cumulative effects from the CBD oil, DHA,  MCT oil and keppra. I've always had a suspicion that beneficial oils will help his condition; afterall, the brain is comprised of over 90% fat.  

 The neurologist actually did not seem surprised at the benefits of DHA.  So why the heck didn't he tell me about it before?!  Allopathic doctors only want to push drugs even if they know natural products may work, too.  Is that due to liability issues or because it's not in their scope of practice?  When I shared L's seizure log starting from March up to present he didn't seem surprised nor debunk the results.  At least, he is on board with my new care plan.  The trajectory we would have followed had I strictly followed the neurologist's recommendations would have been to max out on one seizure medication after another until nothing works and the seizures become "intractable".  Then, perhaps a VNS implantation options would be offered along with very restrictive diets. And, if all that fails, brain surgery would be suggested, all the while experiencing some very bad side effects from the medications and regressions from the seizures.  If all those interventions haven't worn out the body or perhaps because of it, there is the very real and scary possibility of dying from SUDEP.  It seems many children with Dup15q have already gone this route and few have even died from SUDEP.  This is all a dismal prospect, to say the least. 

 I don't have any scientific proof or rationale for how it does what it does but after googling  seizures and DHA online, I found page after page of scholarly articles and empirical data that show increase in seizure threshold both in experimental models and in human clinical trials.  Many allude to the connection of EFA to modulation of voltage gated ion channels (so I wasn't crazy afterall when I blabbered on about calcium channels!).  

Here are some papers I found on DHA and resverotrol: 

http://www.medicaldaily.com/fish-oil-low-cost-intervention-epileptics-whose-meds-wont-work-anymore-301952

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4525390/
http://www.dhaomega3.org/Nervous-System/Epilepsy-and-Omega-3-Fatty-Acids
http://www.ncbi.nlm.nih.gov/pubmed/24662925

http://newsroom.ucla.edu/releases/low-doses-of-fish-oil-may-reduce-seizures-in-patients-with-drug-resistant-epilepsy
http://www.ncbi.nlm.nih.gov/pubmed/21554899
http://pubs.sciepub.com/ijcen/2/2/1/
http://www.ncbi.nlm.nih.gov/pubmed/24896336


Here are articles about seizure reduction using MCT oil:

http://www.hindawi.com/journals/crinm/2013/809151/
http://adc.bmj.com/content/61/12/1168.full.pdf


A quote from one article mentions EFA to ion channel excitability.

"This idea is based on the ability of omega-3 fatty acids to cross the secure blood brain barrier, where it then becomes incorporated in the cells’ layers of fat. Once inside, it’s believed that the fatty acids alter calcium and sodium channels, preventing neuronal excitability, and thus seizures. Whether or not this works has been inconsistent, according to past studies."

Currently, I am reading a book cited in one of the articles above. Brain-Building-Nutrition-Physical-Emotional-Intelligence by Michael A. Schmidt, PhD. Here is an excerpt from his book regarding seizures:

There is also evidence that specific saturated fatty acids significantly improve some seizures....In some patients being treated with anticonvulsive drugs, epileptic seizures were reduced by supplementing the diet with 5 g of a spread containing 65% omega-3 fatty acids at every breakfast for six months.

He then cites another book, Fatty Acids: Physiological and Behavioral Function by Dr. David Mostofsy (next on my reading list):

In a chapter devoted to seizures, the authors review multiple biochemical means by which fatty acids might effect seizures....Of particular interest is the second quote, wherein the authors state."At low-micromolar concentrations, they (omega-3 fatty acids, DHA) exhibit the same effects as well known antiepileptic drugs like carbamazepine, phenytoin, and valproic acid....This quote is in specific reference to sodium currents  and voltage gradients...

There is currently a clinical trial study taking place in Canada called Clinical Trial of the Effects of DHA in the Treatment of Seizure Disorders. (click for link)

If time and money were not an issue, I would like to conduct a study and call it "Dose dependent effect of DHA, CBD, MCT and resverotrol on cognition, behavior and seizures in Dup15q population".

I am super excited that L has been seizure free for almost two weeks now.  But, I worry it may just be temporary.  I pray it lasts.  

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Update:  August 11, 2016.  Seizure free for 16 days.  We have reduced keppra down to 300 mg both day and night.  My goal is to be at 250 mg twice a day which was our initial dose.  So grateful and fortunate to have been able to do this for my boy.  

                       

Update:  August 17, 2016.  We are down to 250 mg keppra twice a day.  Day 22 with no seizures noted.  He has achieved a couple of new milestones.  First, he ate his first whole apple without it being chopped up into wedges.  

Second, he has a porcupine doll  that sings the song "Stuck on You" by Sugarland as it spins around in circles.  I was on the sofa and sang the song for him and he thought for a few seconds, walked over to the coffee table that had the doll and brought it to me!!! I never knew he could make that connection!  So exciting! 



Update: August 22, 2016, 27 days seizure free!!  Keppra down to 200 mg twice a day (that's a 60% reduction!).  What looked like a prelude to a seizure in the morning of the first day of kindergarten may have been that he was just half asleep.  He never gets up so early.  We are on a modified schedule at school wherein he starts one hour later than the regular school time so that we can be as gentle as possible with him in the mornings.  

Update: August 25, 2016.  30 days seizure free!! Keppra is down to 180 mg twice a day.  At this point, I am wondering if we can just discontinue the keppra as the dose is below therapeutic range. The neurologist wanted us to initially start at 250mg twice a day so I am assuming anything below that must be non-therapeutic.  In a few days will stop keppra completely and inform neuro of plan.

Update:  September 1, 2016.  Stopped keppra two days ago (August 29).  Still seizure free.  Emailed neuro of plan but received no response back. Wrote down my "recipe" (calculations) for my oil concoction here. 

Update: September 4, 2016.  Lucas as the "summer flu" (which he caught from me) with lots of congestion.  His appetite is poor but wants to eat sweets.  Two days ago, he had sweets all day (chocolate cake, cookie, yogurt, sweetened instant oatmeal, donut, orange juice, honey and lemon water for the congestion).  What the heck was I thinking??? That evening he had a seizure! Was never really convinced that diet made such an impact on seizure onset but now I am.  Gave keppra 250 mg, post-ictal.  Hasn't had a seizure since.  Crossing my fingers.