I have been taking the BCAAs at the same time as my exogenous ketones because I have held the belief for a while now that exogenous ketones could improve drug delivery to the brain (much like the combination of aspirin and caffeine) and research already suggests that brain amino acid metabolism is more efficient in a ketotic state (Yudkoff et al., 2007).
These branched chain amino acids compliment ketogenesis nicely and leucine and lysine in particular are strictly ketogenic amino acids which have shown potent anticonvulsant effects. Its complicated, I know, and the ratio of individual amino acids are important, so I'm still learning and testing blood ketones and blood glucose to assess efficacy.
I am particularly interested in this amino acid supplement from Dr. Heinz Reinwald, who has used it in some very interesting studies for the metabolic management of cancer and to compliment immunotherapy treatments such as in the study below.
Amino acid product and study:
|IMG- Glucogenic and Ketogenic amino acids:|
The effects of all this, and nutritional ketosis in general, can be similar to that of the 'ketogenic diet pill' developed by researchers in Japan. The drug, sitipentol, works primarily by enhancing central Gaba neurotransmission and by inhibiting lactate dehydrogenase, an important enzyme involved in the energy metabolism of neutrons (Sada et al., 2015).
IMPORTANT!!! In cancer, lactate dehydrogenase expression is enhanced as a result of the Warburg Effect (Hirschhaeuser, Sattler, and Mueller-Klieser, 2011) so sitipentol could indeed be very useful not just for seizure control of drug resistant epilepsy, but also to compliment a metabolic protocol for cancer management to take advantage of this metabolic defect.
|IMG- Targeting Lactate Dehydrogenase A inhibits tumourigenesis and tumour progression in mouse models: |
(Xie et al., 2014)
I believe it would likely be effective at therapeutic doses that go beyond seizure control. I would even be more comfortable taking stiripentol than metformin for brain cancer management even though I think they both show great potential. I would simply be more confident of stiripentol offering the specific neurological effects I would be hoping for despite the side effects. I am not entirely convinced that metformin crosses the blood brain barrier at appreciable amounts despite its ability to lower blood glucose so I see sitipentol as being potentially more suitable for brain cancer specifically in theory. It just makes sense to me.
|Stiripentol by Diatomit enhances beneficial effects of the therapeutic ketosis for cancer management by inhibiting lactate dehydrogenase and offers neuroprotection and increased seizure threshold by enhancing central Gaba neurotransmission: http://www.diacomit.eu/en/64-check|
I had already undertaken extensive research into leucine after learning about its very promising results for drug resistant epilepsy in animals. I wrote a long article on this a while ago, but it was deleted which is a little frustrating, however there is a decent summation here of the potential of these ketogenic amino acids, even in isolation for seizure control.- https://www.epilepsy.org.uk/news/news/amino-acid-good-rescue-medication-64819
Supplementation with L-carnitine may be especially useful for patients taking valproic acid (Epilim) as an anticonvulsant because it can result in hormonal dysregulation in both females AND males. These effects in males are rarely documented or even discussed. Men taking VPA display significantly lower free carnitine/total carnitine but it also makes your sperms weaker swimmers (lower motility), lowers testosterone, and raises insulin and C-peptide concentrations (YIKES!) (Røste et al., 2005).
Carnitine also aids fatty acid metabolism of course being an essential cofactor required for long chain fatty acids to enter mitochondria. It aids oxidation of palmitic acid (Seim, Kiess and Richter, 2002) so one could potentially argue (I don't know, just a theory) that maybe that if this palmitic acid is used and not stored as body fat (which would promote systemic inflammation), that these studies suggesting palmitic acid promotes carcinogenesis (Pasqual et al., 2017) may be invalidated from a well constructed dietary perspective. It is also worth noting that the study looked at CD36, which is a fatty acid receptor for oxidised low density lipoprotein (the 'bad' cholesterol), which is often linked to atherosclerosis (Endemann et al., 1993) and shouldn't be a problem on a well structured ketogenic diet. Quite the opposite in fact.
|IMG- Oxidation of fatty acids: carnitine (Flanagan et al., 2010)|
People have different opinions on this, and it is likely that it is actually the ratio of LDL cholesterol and HDL cholesterol is more important or simply HDL on its own (if its too low this is the main problem it seems). On a well structured ketogenic diet LDL cholesterol is unlikely to change much (it may be a little elevated but particle size is the important consideration) but high density lipoprotein (the 'good' cholesterol), usually increases and insulin is normalised.
This would mean that CD36 is unlikely to be expressed to respond, forming a 'foam cell' as shown below. This is called a foam cell because macrophages are recruited to the location of these fatty deposits on blood vessel cell walls. It is a pro-inflammatory response causing the cell to be filled with lipids and this action creates a 'foamy' appearance.
|IMG- Foam Cell https://en.wikipedia.org/wiki/Foam_cell|
|IMG- (Lüscher et al., 2014)|
The ketogenic diet is about using fat for energy and it is excess carbohydrates and trans fats which will cause this type of fat to be stored, creating inflammatory responses. I remain unconvinced that palmitic acid from foods such as ghee and coconut oil will promote carcinogenesis, especially when the fatty acid profile is balanced appropriately and the diet is personalised. Palmitic acid from grass fed and grain fed animals may also be different of course, just a thought. I am no expert of course (I'm always learning, nobody is a true expert), but the basic idea seems to make sense to me.
|IMG- (St-Pierre et al., 2017)|
Maybe I'll have amazing cognitive abilities and be superhuman in some way. It would be good to just feel more normal as I still feel like crap a lot of the time. Telekinesis would be pretty fun though or the ability to read a whole book on a complicated subject in a single day. Kind of like Doctor Strange, that was a cool film, enjoyed it. I like superheroes with intelligence rather than the meathead types.
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