Getting functional on MCTs, lavender oil and cacao - KBs, PPARs, linalool and flavonol goodness

[Alchemica]

Needed to de-stress so I tried some 90% MCT liquid coconut oil (4 X more than virgin coconut oil) spiced with a bit of linalool rich lavender oil. My ratio is a work in progress, my coprolalia was really bad so I did 20mL 90% MCTs, 20g cacao powder and 500mg lavender EO.

Verdict - Nice! Got my stress response down, less coprolalia and feeling those mega stress responses normalising at the transcriptional level, that oxytocin, VDCC blockade, 5-HT1A activity, GABAA modulation through parent and through oxygenated metabolites, NMDAR modulation etc.
 

Nice energy to work with, will be fueling myself with this a bit more in my hot chocolates.
 

Normally lavender oil was thought to be NOT GABAergic. It seems linalool and its metabolites are...

$10 gets you 33 serves of 90% MCTs another ~$15 for a bottle of L. angustifolia that will last yonks, all from the supermarket. My bottle has got me through full blown alcohol withdrawals that should have needed 30mg diazepam...

So there seems to be promising indications for these MCTs in things like MS. When you're like me with significant white matter damage, preserving the brain and boosting energetics is important. Some of these short chain fats are potent PPAR-gamma modulators. The cacao flavonols help with the NO, CBF and BDNF and general brain health, pushing up the ketone bodies and neuroprotective/immune modulating effects of MCTs is helpful for white matter pathology. Don't know if it's assisting remyelination or just optimising the system a bit?

In a small study: Routine haematology, biochemistry and liver function tests gave no indication of harmful side effects from MCT.
 

So out of the PPAR modulators, PPARγ seems like my favourite. PPARα high affinity agonism was interesting but not robustly efficacious. Got my gamma on through various things including carvacrol (dual PPARα/γ), phenolic magnolia lignans, BCP, now my short chain fats from MCTs. Things like decanoic acid efficaciously activate PPARγ receptors

These seem to be beneficial for addiction and white matter disruption... A PPARγ agonist induced a higher likelihood of reduced cocaine craving and improved brain white matter integrity as a function of time in treatment.
 

Agonism of PPARγ induces an anti-neuroinflammatory effect via the phenotypic switch towards the M2-like anti-inflammatory state in glia. PPARγ agonists fine-tune glial phenotypes and functions, mediating anti-inflammatory state of brain glia - may lead to beneficial neuroprotective effects and has therapeutic potential in neuroinflammatory and neurodegenerative diseases.
 

Other natural PPARα modulation can be added as desired with various natural ligands such as oleic acid, linoleic acid, linolenic acid, arachidonic acid (7.9, 17.3, and 60.8 nM, respectively). Interestingly, PPARα agonism induces bHB production.
 

It's likely these improvements are due to the 90% MCTs working synergistically through ketone bodies and PPARs and lavender oil being quite complementary [also boosting ketone bodies being a decent PPARα agonist in addition to the other actions]:
 

1. elevating ketone bodies several fold (being good CNS energy sources + ketone bodies such as beta-hydroxybutyrate (β-HB) reducing neuronal firing rates mediated in part by brain Glu optimisation, changes in GAD65/67 and GABA, activity at adenosine receptors, increased ATP, modulation of calcium channels and most notably Katp channel activity and GABAB signaling.
 

I had a bit of carbs yesterday, wasn't too strict on myself at lunch but for breaky I'm going MCTs and cacao powder. Low carb, high MCTs, relatively low kJs

 

and
 

2. through acting as sources of fatty acids which act on PPARs etc.
 

This has applications in MCI/AD etc:
 

20 subjects with AD or mild cognitive impairment consumed a drink containing emulsified MCTs or placebo. Significant increases in levels of the ketone body beta-hydroxybutyrate (beta-OHB) were observed 90 min after treatment (P=0.007) when cognitive tests were administered. beta-OHB elevations were moderated by apolipoprotein E (APOE) genotype (P=0.036). For 4+ subjects, beta-OHB levels continued to rise between the 90 and 120 min blood draws in the treatment condition, while the beta-OHB levels of 4- subjects held constant (P<0.009). On cognitive testing, MCT treatment facilitated performance on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) for 4- subjects, but not for 4+ subjects (P=0.04). Higher ketone values were associated with greater improvement in paragraph recall with MCT treatment relative to placebo across all subjects (P=0.02).
 

And epilepsy:

MCTs produce a higher level of ketosis compared with long-chain triglycerides, and this allows for a decrease in the intake of these fats and a greater consumption of carbohydrates and protein on this modified diet.
 

The first long-term randomized trial compared the effects of the classic KD and the MCT diet in children with intractable epilepsy after 3, 6, and 12 months on these regimens (28). The 4:1 classic KD was used for the majority of the children, although some children were on a 3:1 ratio. The MCT diet was composed of ∼15% carbohydrates, ∼10% protein, 30% long-chain FAs, and 40–45% MCT fat. There were no differences between dietary groups in percent reduction in baseline seizures after 3, 6, and 12 months. Additionally, no differences were found between the two diets in those achieving seizure reductions greater than 50 or 90%. Serum levels of ACA and BHB were greater in children on the classic KD after 3 and 6 months, but only levels of ACA remained elevated in those on the KD after 12 month
 

- rats fed the KD for 3 weeks showed a reduction in brain glutamate levels, with no change in GABA. Another study in rats fed the KD for 3 weeks found increased levels of glutamate and glutamine in the hippocampus, but this was also associated with an overall decrease in the transcripts of genes involved in synaptic transmission. Further, using both mild CR (i.e., 90% of daily energy requirements or 10% CR) and an isocaloric KD, investigators found significant increases in the mRNA expression of both isoforms of GAD (GAD65 and GAD67) in several brain regions and independent of ketogenic effects. Additionally, reduced levels of aspartate were found in a mouse model of ketosis, along with the expected increases in acetyl-CoA, with no change in the levels of GABA and glutamate. However, this same study also showed increases in glutamine and GABA upon infusion of the nitrogen donors alanine or leucine
 

- enhance reuptake of glutamate from the synaptic cleft by astrocytes The ketone bodies, BHB and ACA, were shown to directly influence presynaptic glutamate release by directly competing with Cl− for allosteric activation of vesicular glutamate transporters, resulting in diminished release of glutamate
 

- In the hippocampus, BHB and ACA did not acutely affect GABAA, α-amino-3-hydroxy-5-methylisoxazole-4-propionate, N-methyl-D-aspartate, kainate, or glycine receptors. However, ACA and BHB were later shown in vitro to reduce the spontaneous firing rate of GABAergic neurons in the substantia nigra pars reticulata, a putative subcortical seizure gate, and this action was dependent on opening of KATP channels and GABAB receptor activation The same group then showed that the open probability of KATP channels in the hippocampus in vitro was enhanced in the presence of BHB Further support for ketone body effects on neuronal excitability was recently demonstrated in sympathetic neurons in vitro. Here, BHB was shown to be an agonist of the FFA receptor 3, through which inhibition of N-type Ca2+ channels was documented Interestingly, the short-chain FAs, acetate, propionate, and butyrate, are known agonists of FFA receptor
 

- Regulate BCL-2-associated agonist of cell death (BAD), a member of the Bcl-2 proteins that govern apoptotic cell death, was found to mediate a switch in the oxidative metabolism of glucose versus ketone bodies
 

- Increases in the levels of the purine nucleotide adenosine may also potently modulate neuronal activity. Adenosine is produced from ATP and itself produces anti-seizure effects through activation of inhibitory adenosine A1 receptors (A1Rs). As the KD increases levels of AT, elevated neuronal or astrocytic release and subsequent hydrolysis to adenosine in the synapse may subsequently result in enhanced activation of A1Rs. In mice, targeted deletion of A1Rs (i.e., A1R+/− and A1R−/−) or increased expression of adenosine kinase (Adk-Tg), an enzyme that enhances clearance of adenosine, causes spontaneous electrographic seizures. A 3 week treatment with a KD led to decreased electrographic seizures in Adk-Tg and A1R+/− mice, but not in animals missing A1Rs (A1R−/−), indicating that adenosine may be an important mediator of the KD’s anti-seizure effects.

Cognition and Synaptic-Plasticity Related Changes in Aged Rats Supplemented with 8- and 10-Carbon Medium Chain Triglycerides

[Alchemica]

These liquid coconut oils (90% MCTs) are like nitromethane for racing fuel... They're additions, you don't want to neglect essential long-chain PUFAs etc in your juiced up high octane body fuels. LA/ALA/Omega-9s etc in your fuel blend... MCT/ω-3 PUFA-enriched diets are associated with a more favorable cytokine and FA profile consistent with attenuated inflammatory responses, really useful. LA is essential. Oleic acid really useful.

How to blend the perfect body fuel?
 

I'm thinking hemp seed oil and liquid coconut oil might be a good start? What ratio though? I want to keep MCTs high initially... Any suggestions?

[Alchemica]

So my maintenance high octane nitro brain fuel is currently 2 parts liquid coconut MCTs 90%, 1 part hemp seed oil, 500mg/15mL oregano oil 15mL of that PRN. Tasty oregano oily goodness! Also have my lavender chill version. Dose as needed depending on circumstances
 

Now I have some cheap carvacrol rich Oregano oil, I'm doping my good oils with that liberally. I like the taste, for one. Good antioxidant to stop PUFA oxidation, too. Not only is this a potent dual PPARα/γ agonist meaning I wont need such high doses to get benefits - I can drop the fat kJs, use less MCTs and get more ketone bodies hypothetically, it's an anti-inflammatory COX modulator, but as I briefly explored awhile back with health food shop pricey diluted EO, when administered for seven consecutive days (12.5 mg/kg p.o.), it was able to increase dopamine and serotonin levels in the prefrontal cortex significantly.

Part of the monoamine modulation is through TRPV3 (also TRPA1 activity is present). It is potently neuroprotective, particularly on DAergic circuits, and exerts many of its effects via caspase-3 and TRPM7

[Sallubrious]

Some of the supermarket MCT's are bit of a rort as I see it. Although they are MCT's many of them (particularly coconut oil MCT's)  are the leftovers after the lauric acid has been removed and sold at a premium.  Sometimes they also remove the caproic acid fraction too because it doesn't taste very good. They do give a quick shot energy though.

 

It's a bit controversial in some respects as the lauric acid has 12 carbon and is a borderline long chain fatty acid, but the lauric acid has so many benefits it's hard for me to get my head around taking a supermarket MCT without it. There's an entire discussion right there on the metabolism of fatty acids with different length carbon chains.

 

The lauric acid fraction is in many ways the most desirable fatty acid in coconut oil, the rest still have value but to pay a premium for an MCT product missing the (arguably) most important one is rip off.

 

I just go for the coconut oil that has seems to have had the least processing

Edited July 15, 2017 by Sallubrious

[Sallubrious]

MCT vs Coconut oil

 

A somewhat biased opinion from a site peddling coconut oil,

[Alchemica]

Thanks, I might look into some sources where the exact fatty acid profile is known

Edited July 15, 2017 by Alchemica

[Alchemica]

So yeah, adding the LA/ALA of hemp seed oil acutely feels nicer than plain coconut MCTs... get those endocannabinoids cranking with your ketone bodies and short-chain fatty acids

Polyunsaturated fatty acids and endocannabinoids in health and disease.

Polyunsaturated fatty acids (PUFAs) are lipid derivatives of omega-3 (docosahexaenoic acid, DHA, and eicosapentaenoic acid, EPA) or of omega-6 (arachidonic acid, ARA) synthesized from membrane phospholipids and used as a precursor for endocannabinoids (ECs). They mediate significant effects in the fine-tune adjustment of body homeostasis. Phyto- and synthetic cannabinoids also rule the daily life of billions worldwide, as they are involved in obesity, depression and drug addiction. Consequently, there is growing interest to reveal novel active compounds in this field. Cloning of cannabinoid receptors in the 90s and the identification of the endogenous mediators arachidonylethanolamide (anandamide, AEA) and 2-arachidonyglycerol (2-AG), led to the characterization of the endocannabinoid system (ECS), together with their metabolizing enzymes and membrane transporters. Today, the ECS is known to be involved in diverse functions such as appetite control, food intake, energy balance, neuroprotection, neurodegenerative diseases, stroke, mood disorders, emesis, modulation of pain, inflammatory responses, as well as in cancer therapy. Western diet as well as restriction of micronutrients and fatty acids, such as DHA, could be related to altered production of pro-inflammatory mediators (e.g. eicosanoids) and ECs, contributing to the progression of cardiovascular diseases, diabetes, obesity, depression or impairing conditions, such as Alzheimer' s disease. Here we review how diets based in PUFAs might be linked to ECS and to the maintenance of central and peripheral metabolism, brain plasticity, memory and learning, blood flow, and genesis of neural cells.
 

Previous studies indicate that a 4:1 ratio (n-6 to n-3) diet is sufficient to greatly reduce mortality and improve health parameters, whereas the usual western diet provides 15:1-16.7:1 ratios of n-6/n-3, leading to obesity, cardiovascular disease, cancer, inflammatory, and autoimmune disorders.

 

Therefore, the correct regulation of peripheral and central metabolic pathways is dependent on the adequate ingestion of PUFAs. In humans and in experimental obesity induced by western diets, an increase of n-6 to n-3 ratio has been observed, as well as an overactivation of the central and circulating ECs. Understanding how the balance between n-3 versus n-6 enriched PUFA impacts the EC content and synaptic activity in the CNS is crucial to reveal novel therapeutic and nutritional approaches that may prevent and/or contribute to the recovery of impaired regulation of pain, cognition, mood, behavior, and metabolism.
 

Here we review PUFA’s essential role on the expression and function of cannabinoid receptors, highlighting recent discoveries and the impact of the endocannabinoid system (ECS) on common brain and neuroendocrine disorders, as it is seen in neurodegenerative and metabolic diseases.
 

Full text: http://sci-hub.bz/10.1080/1028415x.2017.1347373

Edited July 16, 2017 by Alchemica

[Anodyne]

Sorry if this is a stupid question, but why are you buying a product where the PUFAs have been removed, and then adding PUFAs back in? Wouldn't it be cheaper & simpler to just use coconut oil? Or is there some specific blend/ratio that you're aiming for that can't be achieved with coconut oil?

[Alchemica]

No stupid questions! I wanted to get a feel for the purer MCTs out of interest. I didn't think the coconut oils PUFAs (what % are they? cant see any good specs) were particularly good for healing in their what I understood to be low quantities? I've been using virgin coconut oil for awhile, it was OK but these blends seem nicer. I can play with reconstituted versions more! I just get better specs on my hemp seed oil and stuff which allows me to dose them with healing in mind. I'll look into it.

 

https://theconsciouslife.com/omega-3-6-9-ratio-cooking-oils.htm

 

Edited July 16, 2017 by Alchemica

[Alchemica]

So in addition to this, as mentioned in the phytoestrogens thread, later this week I'll get healthy doses, low doses, of genistein into me. I'll keep rolling with the oils and cacao - I'm happy that I'm getting some new found frontal cortical stuff happening particularly with the help of flavonols, Cacao is nicely cerebral, but to me, my hippocampal-dependent stuff seems less well intact. Genistein is a cheap thing to add to see what's recoverable.

I'm using genistein as it's a potent ERβ agonist and serotonergic - antidepressive, neuroprotective and even has possible use in things like PTSD. Other benefits include anti-carcinogenic effects which are seen in the range of 10-20mg/kg bodyweight a day but I'll start low. As an added benefit, genistein appears to inhibit adipogenesis as well as induce fat cell apoptosis via AMPK
 

Estrogens through ERβ improved many aspects of deleterious effects of brain injury on the hippocampus, including neuronal apoptosis, dysfunction in spatial memory, reduction in NR2B, enhancement of oxidative stress, and activation of ERK1/2 pathway. E2 has therapeutic potential for both prevention and intervention of induced brain damages.
 

Modulating this system improves attention, memory, learning and the associated brain activity in chronically ill men and women with psychosis-spectrum disorders.

In addition:
 

So since I've recently drastically cut dairy just as I haven't felt like having it, I may need to supplement calcium or get back into something calciumy? I'm getting good doses of magnesium now through cacao which I really like and Mg is getting backing in the recent literature for depression and anxiety but dropping calcium is not good - low calcium levels can affect your sense of well-being and cause changes in your behavior. Again, lethargy, anxiety, jitters, depression and irritability are common.
 

Calcium and magnesium have a complicated relationship that is not fully understood. The human body needs adequate levels of magnesium in order to properly use calcium, and magnesium deficiency affects calcium metabolism and alters levels of certain hormones that regulate calcium in the body. The two minerals may also compete with other and interfere with the other's function. For example, magnesium may prevent calcium from properly contracting muscles when the ratio of magnesium to calcium is incorrect.

Seeing I get a couple hundred milligrams Mg a day from Cacao alone, definitely worth putting some 333mg Ca +D tablets in and seeing what that does. RDI for me for Mg is 400 mg/day and Ca about 1,000mg

 

I'll start upping my calcium today.

[ThunderIdeal]

On 15/07/2017 at 11:56 PM, Sallubrious said:

Some of the supermarket MCT's are bit of a rort as I see it. Although they are MCT's many of them (particularly coconut oil MCT's)  are the leftovers after the lauric acid has been removed and sold at a premium.  Sometimes they also remove the caproic acid fraction too because it doesn't taste very good. They do give a quick shot energy though.

 

It's a bit controversial in some respects as the lauric acid has 12 carbon and is a borderline long chain fatty acid, but the lauric acid has so many benefits it's hard for me to get my head around taking a supermarket MCT without it. There's an entire discussion right there on the metabolism of fatty acids with different length carbon chains.

 

The lauric acid fraction is in many ways the most desirable fatty acid in coconut oil, the rest still have value but to pay a premium for an MCT product missing the (arguably) most important one is rip off.

 

I just go for the coconut oil that has seems to have had the least processing

 

Im really glad you brought this to my attention sally, when i first sought mct it seemed to be a specialist health food? But now i see its indeed in supermarkets at premium cost proclaiming its superiority over virgin coconut oil;  in fact it's a byproduct.

 

Leaves a bad taste in my mouth, figuratively AND literally.

 

Caprylic

adjective

1. of or relating to an animal odor:the caprylic odor of a barn.

 

decanoic acid is synonymous with capric acid which means smelling of goats.

 

Though the webstore I originally used is apparenrly mum on the matter of its product's composition, the bottle reveals it has no lauric acid.

Edited July 24, 2017 by ThunderIdeal

[Alchemica]

Thanks for that feople.

Resonating on a stated %lauric coconut oil (51% lauric) to see how that feels with my cacao and genistein for breakfast. A bit cheaper than my 90% MCTs liquid coconut oil... I might have to look into some better MCTs one day. This is a cheap cooking coconut oil with stated LA%... it has no coconut taste but a pleasant creaminess. I felt better using coconut oil with my cacao so back to that. Should get the added goodness of the soy isoflavone, too.
 

It has a role in optimising brain energetics and elevating ketone bodies which exert neuroprotective effects, the moderate ketosis induced by regular MCT ingestion may have neuroprotective potential.

Experimental studies have suggested its antioxidant, anti-inflammatory, immunostimulatory and hypolipidemic effects. LA reduces blood pressure in normotensive and hypertensive rats. LA increased PPARα transactivation and acts as a partial agonist at PPARγ and reverses adipose tissue insulin resistance. LA also activated the G protein-coupled receptor 84 (GPR84), regulating inflammation, and PI3K/Akt signaling pathway.

These oil constituents shouldn't be seen in isolation: octanoic or lauric acid also provided protection against Aβ, but was not as effective as the complete oil. The coconut oil treatment reduced the number of cells with cleaved caspase and ROS labeling, as well as rescuing the loss of synaptophysin labeling observed with Aβ treatment.

Treatment with coconut oil, as well as octanoic, decanoic and lauric acids, resulted in a modest increase in ketone bodies compared to controls. The biochemical data suggest that Akt and ERK activation may contribute to the survival promoting influence of coconut oil.