4019 replies to this topic

[BigPapaChakra]

 

WIth DHA, it would make sense to use forms in the sn-2 glycerol position as they are incorporated into neural lipid structures more readily

Hey Papa, thanks for the info. The site that you linked to specifically indicates that DHA-EE was better for those with Peroxisomal Biogenesis Disorders which disrupts fat metabolism. Is there any evidence (studies) that it is better for those without such disorders?

 

Also, there is evidence (in cell studies) that DHA is incorporated into mitochondrial cardiolipin. How would the DHA-EE form affect it's absorption and activity in mitochondria?

 

 

Well, DHA-EE is less well studied than plane ol' DHA. My main point overall was that DHA in supplemental form - unless one finds a very specific fish/krill oil that specifies this - is not as efficient for getting DHA into neural lipids; it needs to be in the sn-2 position, which is predominantly in seafood. On a facebook group a guy posted a fish oil in the sn-2 position, but he seemed to have relations to the company or something, idk, it was kinda.... "fishy"  

 

Yet, DHA-EE does have animal evidence and some evidence in other human studies and case studies, though primarily for problems with myelinogenesis: 

 

http://www.ncbi.nlm....ubmed/11944198 

Dose-response effect of docosahexaenoic acid ethyl ester on maze behavior and brain fatty acid composition in adult mice.

The dose-response effect of dietary docosahexaenoic acid (DHA, 22:6 n-3) ethyl ester (EE) on maze-learning ability in mice was studied. Male Crj:CD-1 mice aged three months were fed a) a diet containing 5 g palm oil/100 g diet (control group); b) a diet containing 0.5 g DHA ethyl ester/100 g diet plus 4.5 g palm oil/100 g diet (DHA-EE 0.5% group); c) a diet containing 1 g DHA ethyl ester/100 g diet plus 4 g palm oil/100 g diet (DHA-EEE 1% group); d) a diet containing 2 g DHA ethyl ester/100 g diet plus 3 g palm oil/100 g diet (DHA-EE 2% group) for four months. Maze-learning ability was assessed three months after the start of the experiment. The time required to reach the maze exit and the number of times that a mouse strayed into blind alleys in the maze were measured in three trials, performed every four days. In trial 1, the DHA-EE 0.5%, 1% and 2% groups required less (p < 0.05) time to reach the maze exit, and the DHA-EE 2% group strayed (p < 0.05) into blind alleys fewer times than the control group. In trial 3 performed four days after the second trial, the DHA-EE 2% group needed less (p < 0.05) time to find the exit and spent a fewer (p < 0.05) number of times in blind alleys than did the control group. In the total lipids of plasma and brain of mice fed DHA, increasing intakes of DHA resulted in an increase in DHA levels, with a corresponding decrease in arachidonic acid (20:4 n-6). Improved maze-learning ability in mice fed DHA-EE 2% was associated with higher DHA levels in brain. Our resulted suggest that there are no linear dose-response effects of DHA on maze-learning ability, however, the intake of DHA-EE 2% diet improves learning ability in adult mice as demonstrated by maze performance.

 

^searching for the full-text on libgen, but it would appear from the abstract that DHA-EE readily impacts neural tissue with it being accrued in the brain.

 

http://jn.nutrition....30/6/1629.long 

Intakes of Dietary Docosahexaenoic Acid Ethyl Ester and Egg Phosphatidylcholine Improve Maze-Learning Ability in Young and Old Mice¹

 

The effect of dietary docosahexaenoic acid (DHA) [22:6 (n-3)] ethyl ester (EE) and egg-phosphatidylcholine (PC) on maze-learning ability in young and old mice was studied. Male Crj:CD-1 mice aged either 3 wk or 14 mo were fed a diet containing 2 g DHA-EE/100 g diet plus 3 g palm oil/100 g diet (DHA-EE Group), 5 g egg-PC/100 g diet (egg-PC Group), 1 g DHA-EE/100 g diet plus 2.5 g egg-PC/100 g diet plus 1.5 g palm oil/100 g diet (DHA-EE + egg-PC Group) or 5 g palm oil/100 g diet (Control Group) for 5 mo. Maze-learning ability was assessed 4 mo after the start of the experiment. The time required to reach the maze exit and the number of times that a mouse strayed into blind alleys in the maze were measured in three trials every 4 d. In trial 2 of young mice, performed on d 4 after the first trial, the DHA-EE group required less (P < 0.05) time to reach the maze exit and DHA-EE and egg-PC groups strayed (P < 0.05) into blind alleys fewer times than the control group. In trial 2 of old mice, the DHA-EE, egg-PC and DHA-EE + egg-PC groups needed less (P < 0.05) time to find the exit and spent a fewer (P < 0.05) number of times in blind alleys than did the control group. The DHA-EE, DHA-EE + egg-PC and egg-PC groups strayed into blind alleys fewer times than the control group in trial 3 of old mice (P < 0.05). Our results suggest that the intake of DHA-EE and the egg-PC diet effectively enhances maze-learning ability and brain functions in old mice.

 

^Thus, it wasn't only egg-PC or DHA-EE+egg-PC; DHA-EE had benefits all by itself.

 

I've been contemplating getting a large amount of caprylic acid (which I use on and off) and DHA-EE and using a minimum of 2-3 tbsp caprylic acid (for BHB)/day + 1.1g of DHA from DHA-EE in addition to increasing seafood intake a bit.

 

Also, I suspect neural and cranial DHA levels can greatly enhance LLLT:

 

 

A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution. 

Six hundred million years ago, the fossil record displays the sudden appearance of intracellular detail and the 32 phyla. The "Cambrian Explosion" marks the onset of dominant aerobic life. Fossil intracellular structures are so similar to extant organisms that they were likely made with similar membrane lipids and proteins, which together provided for organisation and specialisation. While amino acids could be synthesised over 4 billion years ago, only oxidative metabolism allows for the synthesis of highly unsaturated fatty acids, thus producing novel lipid molecular species for specialised cell membranes. Docosahexaenoic acid (DHA) provided the core for the development of the photoreceptor, and conversion of photons into electricity stimulated the evolution of the nervous system and brain. Since then, DHA has been conserved as the principle acyl component of photoreceptor synaptic and neuronal signalling membranes in the cephalopods, fish, amphibian, reptiles, birds, mammals and humans. This extreme conservation in electrical signalling membranes despite great genomic change suggests it was DHA dictating to DNA rather than the generally accepted other way around. We offer a theoretical explanation based on the quantum mechanical properties of DHA for such extreme conservation. The unique molecular structure of DHA allows for quantum transfer and communication of π-electrons, which explains the precise depolarisation of retinal membranes and the cohesive, organised neural signalling which characterises higher intelligence.

 

The full-text is quite amazing, really. 

[montana2012]

Super Omega-3 EPA/DHA with sesame lignans and olive oil extract" is my source of DHA these days. I trust the brand a lot. The type of fish is specified on the back of the bottle, but not the glycerol backbone:

 

 

Edited by montana2012, 18 April 2015 - 11:33 PM.

[Jochen]

Super Omega-3 EPA/DHA with sesame lignans and olive oil extract" is my source of DHA these days. I trust the brand a lot. The type of fish is specified on the back of the bottle, but not the glycerol backbone:

 

 

 

from the look of it is probably LEF (which I also take, just a different form).

 

for a fact based overview of different fish oil supplement, I find this helpful: https://labdoor.com/rankings/fish-oil

[lostfalco]

Tadalafil (and sildenafil) and mitochondrial biogenesis. Tadalafil enhances nitric oxide signaling, enhances Sirt1 activity, enhances PGC1a, causes mitochondrial biogenesis. 

 

http://www.ncbi.nlm....pubmed/24727492

 

Am J Physiol Heart Circ Physiol. 2014 Jun 1;306(11):H1558-68. doi: 10.1152/ajpheart.00865.2013. Epub 2014 Apr 11.

Chronic inhibition of phosphodiesterase 5 with tadalafil attenuates mitochondrial dysfunction in type 2 diabetic hearts: potential role of NO/SIRT1/PGC-1α signaling.

Koka S1, Aluri HS2, Xi L1, Lesnefsky EJ3, Kukreja RC4.

Author information

Abstract

Enhanced nitric oxide (NO) production is known to activate silent information regulator 1 (SIRT1), which is a histone deacetylase that regulates PGC-1α, a regulator of mitochondrial biogenesis and coactivator of transcription factors impacting energy homeostasis. Since phosphodiesterase-5 inhibitors potentiate NO signaling, we hypothesized that chronic treatment with phosphodiesterase-5 inhibitor tadalafil would activate SIRT1-PGC-1α signaling and protect against metabolic stress-induced mitochondrial dysfunction in diabetic hearts. Diabetic db/db mice (n = 32/group; 40 wk old) were randomized to receive DMSO (10%, 0.2 ml ip) or tadalafil (1 mg/kg ip in 10% DMSO) for 8 wk. Wild-type C57BL mice served as nondiabetic controls. The hearts were excised and homogenized to study SIRT1 activity and downstream protein targets. Mitochondrial function was determined by measuring oxidative phosphorylation (OXPHOS), and reactive oxygen species generation was studied in isolated mitochondria. Tadalafil-treated diabetic mice demonstrated significantly improved left ventricular function, which is associated with increased cardiac SIRT1 activity. Tadalafil also enhanced plasma NO oxidation levels, myocardial SIRT1, PGC-1α expression, and phosphorylation of eNOS, Akt, and AMPK in the diabetic hearts. OXPHOS with the complex I substrate glutamate was decreased by 50% in diabetic hearts compared with the nondiabetic controls. Tadalafil protected OXPHOS with an improved glutamate state 3 respiration rates. The increased reactive oxygen species production from complex I was significantly decreased by tadalafil treatment. In conclusion, chronic treatment with tadalafil activates NO-induced SIRT1-PGC-1α signaling and attenuates mitochondrial dysfunction in type 2 diabetic hearts.

 

 

http://www.ncbi.nlm....pubmed/24042162

 

J Pharmacol Exp Ther. 2013 Dec;347(3):626-34. doi: 10.1124/jpet.113.208017. Epub 2013 Sep 16.

cGMP-selective phosphodiesterase inhibitors stimulate mitochondrial biogenesis and promote recovery from acute kidney injury.

Whitaker RM1, Wills LP, Stallons LJ, Schnellmann RG.

Author information

Abstract

Recent studies demonstrate that mitochondrial dysfunction is a mediator of acute kidney injury (AKI). Consequently, restoration of mitochondrial function after AKI may be key to the recovery of renal function. Mitochondrial function can be restored through the generation of new, functional mitochondria in a process called mitochondrial biogenesis (MB). Despite its potential therapeutic significance, very few pharmacological agents have been identified to induce MB. To examine the efficacy of phosphodiesterase (PDE) inhibitors (PDE3: cAMP and cGMP activity; and PDE4: cAMP activity) in stimulating MB, primary cultures of renal proximal tubular cells (RPTCs) were treated with a panel of inhibitors for 24 hours. PDE3, but not PDE4, inhibitors increased the FCCP-uncoupled oxygen consumption rate (OCR), a marker of MB. Exposure of RPTCs to the PDE3 inhibitors, cilostamide and trequinsin, for 24 hours increased peroxisome proliferator-activated receptor γ coactivator-1α, and multiple mitochondrial electron transport chain genes. Cilostamide and trequinsin also increased mRNA expression of mitochondrial genes and mitochondrial DNA copy number in mice renal cortex. Consistent with these experiments, 8-Br-cGMP increased FCCP-uncoupled OCR and mitochondrial gene expression, whereas 8-Br-cAMP had no effect. The cGMP-specific PDE5 inhibitor sildenafil also induced MB in RPTCs and in vivo in mouse renal cortex. Treatment of mice with sildenafil after folic acid-induced AKI promoted restoration of MB and renal recovery. These data provide strong evidence that specific PDE inhibitors that increase cGMP are inducers of MB in vitro and in vivo, and suggest their potential efficacy in AKI and other diseases characterized by mitochondrial dysfunction and suppressed MB.

 

Edited by lostfalco, 19 April 2015 - 05:02 PM.

[NeuroGeneration]

lostfalco – have you come across any information that may explain how CoQ10 & Ubiquinol would cause excessive fatigue?

 

For months I was going crazy trying to figure out what was making me feel so terrible. I went as far as getting sleep studies done, seeing a psychiatrist, my GP, endocrinologist, etc., all to no avail.

 

I ran out of CoQ10 for a week and felt amazing – like my normal self again! I've tried a few ubiquinol / ubiquinone pills here and there to test out my theory, and without fail, they wipe me, requiring a long nap within two hours. They also screw with my sleep, even when taken in the morning. I wake up multiple times, and never feel like I got a sound night's sleep.

 

Could it be over-activating my mitochondria? Something else? I've done some snooping around on LongeCity & other sites and have found that a lot of other people have reported the same, but have failed to find an explanation.

 

Any theories?

[mettmett]

What brand of coq10 are you using

[NeuroGeneration]

I've used a few. LifeExtension, NOW, Jarrow, and a couple others that I can't remember at the moment.

[De La Torre]

Just as an aside. Falco, I'm curious as to the reason you decided to start supplementing pregnenalone, and whether you still do? It seems that unless one has a hormonal imbalance going on, pregnenalone can be rather detrimental to one's entire physiology. I know that you're very sensible with your supplementing, and don't take anything without a fair amount of background research first. I'm going on the assumption that you have a healthy hormonal system. I'm about to start your tulip protocol, and feel that this is the only dodgy aspect of what seems like a well rounded system of neurological enhancement.

Edited by De La Torre, 23 April 2015 - 02:20 AM.

[montana2012]

I feel like it's high time we solve the dilemma of fish oil supps vs actual seafood. There's so much contradictory data out there, we don't know which studies are backed by supplement companies, which are genuine. I personally love seafood, but it's more convenient and time efficient ( yeah, I know, don't lash at me ) to take the pills. I though I was in safe water with buying the LEF brand, but I'm now thinking about reverting back to fish for good and never bothering with the topic again. I'm a little grumpy.

[xls]

Well, heat will oxidize fish oil supplements. If the oil is kept cold and dark from the moment of its extraction all the way to your mouth fish oil is good. Problem is, this doesn't really happen for most fish oil. LEF I think keeps it cold immediately after extraction, but if it gets shipped from a warm location it will degrade the quality. Be skeptical of fish oil that smells "fishy" esp excessively so, this is a sign of oxidation.

 

I prefer seafood because theres tons of benefits besides just DHA like b vitamins, selenium, vitamin d, protein.

[Jochen]

lostfalco – have you come across any information that may explain how CoQ10 & Ubiquinol would cause excessive fatigue?

 

For months I was going crazy trying to figure out what was making me feel so terrible. I went as far as getting sleep studies done, seeing a psychiatrist, my GP, endocrinologist, etc., all to no avail.

 

I ran out of CoQ10 for a week and felt amazing – like my normal self again! I've tried a few ubiquinol / ubiquinone pills here and there to test out my theory, and without fail, they wipe me, requiring a long nap within two hours. They also screw with my sleep, even when taken in the morning. I wake up multiple times, and never feel like I got a sound night's sleep.

 

Could it be over-activating my mitochondria? Something else? I've done some snooping around on LongeCity & other sites and have found that a lot of other people have reported the same, but have failed to find an explanation.

 

Any theories?

 

well from anecdotal stories, and I am by no means an expert, but my layman terms understanding is the following:

 

• Q10 optimises the energy output in your mitochondria, but also ensures you have less of them. (less but more efficient ones)
• PQQ actually takes care of mitochondria genesis (so making more mitochondria)

What some anecdotes refer to is that some people actually have a crash after taking Q10 for a while. I always assumed these people where only taking Q10 and not together with PQQ.

I guess for those people it is best to cycle it.

 

My thought on this was that the combination of both PQQ and Q10 would make sure you have best of both worlds and would not generate this crash.

But as we all know, we are all unique in our own way and it's obvious this is affecting a lot of us differently.

 

Some people do experience a crash of reduced energy from what I can tell after stopping Q10-PQQ. Some feel tired for a day or two. (less energy output in mitochondria again)

 

I personally cycle it these days (only use QC10-PQQ on days with LTT). Weekdays I typically use low dose PQQ and MitoQ.

 

Believe that Joe wrote something about these effects as well on his blog http://selfhacked.co...ment_With_MitoQ(might be a start).

 

Bottomline, tune in to your body and listen to it.

 

anyhow just my two cents.

[montana2012]

Well, heat will oxidize fish oil supplements. If the oil is kept cold and dark from the moment of its extraction all the way to your mouth fish oil is good. Problem is, this doesn't really happen for most fish oil. LEF I think keeps it cold immediately after extraction, but if it gets shipped from a warm location it will degrade the quality. Be skeptical of fish oil that smells "fishy" esp excessively so, this is a sign of oxidation.

 

I prefer seafood because theres tons of benefits besides just DHA like b vitamins, selenium, vitamin d, protein.

I take vit. D, brazil nut, shoot up B vitamins on the side, so I'm really loaded on the rest of the beneficial substances. What I really need is bioavailable DHA (in the sn2 position), because I spend a lot of time in a blue light environment. I always take my fish oil with fat for better absorption, seems like, however, that even that's not a guarantee. I need at least 1 gram of DHA daily in my bloodstream. Also, I don't feel like spending money on a fatty acid test.  

Edited by montana2012, 23 April 2015 - 02:55 PM.

[NeuroGeneration]

 

lostfalco – have you come across any information that may explain how CoQ10 & Ubiquinol would cause excessive fatigue?

 

For months I was going crazy trying to figure out what was making me feel so terrible. I went as far as getting sleep studies done, seeing a psychiatrist, my GP, endocrinologist, etc., all to no avail.

 

I ran out of CoQ10 for a week and felt amazing – like my normal self again! I've tried a few ubiquinol / ubiquinone pills here and there to test out my theory, and without fail, they wipe me, requiring a long nap within two hours. They also screw with my sleep, even when taken in the morning. I wake up multiple times, and never feel like I got a sound night's sleep.

 

Could it be over-activating my mitochondria? Something else? I've done some snooping around on LongeCity & other sites and have found that a lot of other people have reported the same, but have failed to find an explanation.

 

Any theories?

 

well from anecdotal stories, and I am by no means an expert, but my layman terms understanding is the following:

 

• Q10 optimises the energy output in your mitochondria, but also ensures you have less of them. (less but more efficient ones)
• PQQ actually takes care of mitochondria genesis (so making more mitochondria)

What some anecdotes refer to is that some people actually have a crash after taking Q10 for a while. I always assumed these people where only taking Q10 and not together with PQQ.

I guess for those people it is best to cycle it.

 

My thought on this was that the combination of both PQQ and Q10 would make sure you have best of both worlds and would not generate this crash.

But as we all know, we are all unique in our own way and it's obvious this is affecting a lot of us differently.

 

Some people do experience a crash of reduced energy from what I can tell after stopping Q10-PQQ. Some feel tired for a day or two. (less energy output in mitochondria again)

 

I personally cycle it these days (only use QC10-PQQ on days with LTT). Weekdays I typically use low dose PQQ and MitoQ.

 

Believe that Joe wrote something about these effects as well on his blog http://selfhacked.co...ment_With_MitoQ(might be a start).

 

Bottomline, tune in to your body and listen to it.

 

anyhow just my two cents.

 

Thanks for your comment. Interesting thoughts.

 

I was taking 10mg of PQQ with my coq10, though.

 

Is it possible to make mitochondria too efficient?

 

Is it possible to have too much CoQ10? What impact would that have on the methylation cycle?

[lostfalco]

lostfalco – have you come across any information that may explain how CoQ10 & Ubiquinol would cause excessive fatigue?

 

I haven't seen anything in the scientific literature but John Brisson has theorized about it a little bit. 

 

http://forum.bulletp...ing/#entry31986

 

http://fixyourgut.co...drial-function/

 

"The only theorized “side effect” (other than the systemic few allergic reactions reported with ubiquinol supplementation, which can happen with any supplement or medication) is that ubiquinol may have a rebound effect if discontinued quickly, if you had been taking the supplement for a while. The rebound side effects are that you might feel tired, weak, and your blood pressure might increase marginally during this period for about a week. Your body synthesizes less CoQ10 and converts less ubiquinol when you are supplementing ubiquinol, so the body can have difficulty producing CoQ10 in the amounts needed to adequately function for a few days if you discontinue the supplement quickly. This difficulty is also known as a rebound effect."

[lostfalco]

My 808nm 200mW laser from Ebay arrived today. It was supposed to be focusable but I have been unable to change the shape of it from a small rectangle. I also bought 808nm protective glasses that makes the laser-rectangle invisible.

 

Any suggestions for how to proceed.

Hey Cosmicalstorm, when I was testing the ebay lasers I usually tried to imitate the locations used in the human studies. Check out human study number 5. http://www.longecity...ts/#entry582938

[BarrelBoy]

I'm curious if anyone who has hairloss and has been lasering for over 6 months with the 850nm light has experienced any regrowth. The laser products targeted for hair growth are generally in the 600nm range, but the only reasoning I can find for why that is is that the light only needs to penetrate the skin and not the brain, which the 800nm range apparently can. I also realize that most hairloss protocols advise 12-20 minutes 3 times a week, so I don't expect many people to be lasering their scalp/brain for that long, but I'm curious nonetheless.

 

EDIT: Also, if one wanted to avoid targeting the brain too long with the 850nm would holding the diodes 1-1.5 inches off the scalp accomplish this while still penetrating the scalp? Anyone think this would work?

 

Sorry if this is too off topic here. I can move it need be.

Edited by brokenyoga, 27 April 2015 - 06:50 PM.

[lostfalco]

Just as an aside. Falco, I'm curious as to the reason you decided to start supplementing pregnenalone, and whether you still do? It seems that unless one has a hormonal imbalance going on, pregnenalone can be rather detrimental to one's entire physiology. I know that you're very sensible with your supplementing, and don't take anything without a fair amount of background research first. I'm going on the assumption that you have a healthy hormonal system. I'm about to start your tulip protocol, and feel that this is the only dodgy aspect of what seems like a well rounded system of neurological enhancement.

Hey De La Torre, I'm still supplementing with Pregnenolone. I've seen a number of anecdotes in which people reported a bad reaction but I haven't noticed anything like this in the literature. In fact, I've seen doses of over 500mg/day for over 3 years given to psychiatric patients with no adverse events reported. Do you have any studies that indicate that it's detrimental?

[De La Torre]

I've read copious reports of bad reactions, but nothing detrimental in any scientific literature, so far. I'm in my early 40's, and feel that this would probably compensate greatly for my constant lethargy. I've been sun gazing for a couple of years now, (on and off due to incessant geoengineering), so am only up to the 26 minute mark. Interestingly, I've been using St Johns Wort the entire time, with no ill effects. I gaze whenever I can, and have lasered my entire head, every 2nd day for 30 seconds, for the last week. Now up to 1 minute per site, left hemisphere one day, then right the next, with a day off in between. So far, very subtle. Though given time, and with the addition of the supplements, when they arrive, I'll be off and racing! Much love bro. And thanks for all your time and knowledge!

Edited by De La Torre, 28 April 2015 - 04:07 AM.

[lostfalco]

I guess I should have known (since butyrate is an HDACi)...but I just found out that beta hydroxybutyrate inhibits HDAC1 and HDAC2! Very cool. What's especially cool is the connection between metabolism and epigenetics. This stuff never ceases to surprise me. 

 

http://www.pubmed.co...les/PMC3735349/

 

"βOHB appears to induce local histone acetylation at the promoter of oxidative stress resistance genes, Foxo3a and Mt2, by inhibiting activity of HDACs 1 and 2."

 

"Inhibition of HDACs by βOHB might contribute to the beneficial effect of ketogenic diets and may be one mechanism by which calorie restriction confers health benefits."

 

"Our observation that βOHB is an endogenous HDAC inhibitor present in organisms at millimolar concentrations during prolonged fasting and CR reveals an example of integration between metabolic status and epigenetic changes."

 

Science. 2013 Jan 11;339(6116):211-4. doi: 10.1126/science.1227166. Epub 2012 Dec 6.

Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor.

Shimazu T1, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD, Newgard CB, Farese RV Jr, de Cabo R, Ulrich S, Akassoglou K, Verdin E.

Author information

Abstract

Concentrations of acetyl-coenzyme A and nicotinamide adenine dinucleotide (NAD(+)) affect histone acetylation and thereby couple cellular metabolic status and transcriptional regulation. We report that the ketone body d-β-hydroxybutyrate (βOHB) is an endogenous and specific inhibitor of class I histone deacetylases (HDACs). Administration of exogenous βOHB, or fasting or calorie restriction, two conditions associated with increased βOHB abundance, all increased global histone acetylation in mouse tissues. Inhibition of HDAC by βOHB was correlated with global changes in transcription, including that of the genes encoding oxidative stress resistance factors FOXO3A and MT2. Treatment of cells with βOHB increased histone acetylation at the Foxo3a and Mt2 promoters, and both genes were activated by selective depletion of HDAC1 and HDAC2. Consistent with increased FOXO3A and MT2 activity, treatment of mice with βOHB conferred substantial protection against oxidative stress.

 

Edited by lostfalco, 05 May 2015 - 11:53 PM.

[lostfalco]

Another fascinating article. Worth the read if you have the time. 

 

http://www.ncbi.nlm....les/PMC4176946/

 

"Intriguingly, the ketone body β-hydroxybutyrate (βOHB) might also be a metabolic intermediary of the benefits of CR and fasting. Long viewed as a simple carrier of energy from the liver to peripheral tissues during prolonged fasting or exercise, βOHB also possesses signaling activities, perhaps most intriguingly as an endogenous inhibitor of HDACs [5]. Thus, it joins a small but growing list of metabolic intermediaries that affect gene expression via chromatin modifications [6]."

 

"The finding that βOHB is an inhibitor of HDACs, together with the coincidence of biological effects of ketone bodies and HDAC inhibition, suggests the fascinating possibility that βOHB could be an endogenous avenue to attain some of the benefits of lifespan extension seen with HDAC inhibition in model organisms."

 

Trends Endocrinol Metab. 2014 Jan;25(1):42-52. doi: 10.1016/j.tem.2013.09.002. Epub 2013 Oct 18.

Ketone bodies as signaling metabolites.

Newman JC1, Verdin E2.

Author information

Abstract

Traditionally, the ketone body β-hydroxybutyrate (βOHB) has been looked upon as a carrier of energy from liver to peripheral tissues during fasting or exercise. However, βOHB also signals via extracellular receptors and acts as an endogenous inhibitor of histone deacetylases (HDACs). These recent findings support a model in which βOHB functions to link the environment, in this case the diet, and gene expression via chromatin modifications. We review the regulation and functions of ketone bodies, the relationship between ketone bodies and calorie restriction, and the implications of HDAC inhibition by the ketone body βOHB in the modulation of metabolism and in diseases of aging.

 

Edited by lostfalco, 06 May 2015 - 02:57 AM.

[lostfalco]

In light of this recent info on beta hydroxybutyrate I just purchased this to try out. http://www.amazon.co...a/dp/B00U7R7194

 

Has anyone tested this out before?

 

It looks like it was created by our old friend Patrick Arnold (of Balco fame, infamy?). Anyway, he makes some really interesting products over at Prototype Nutrition and I may give his Ursolic Acid spray another run once it's back in stock. http://prototypenutrition.com

[Kalliste]

I have not been able to read the thread in it's entirety Falco, but if you like ketones, have you tried "real" fasting?

It's my suspicion that it is a superior alternative to induce ketones. Valter Longo has produced some very positive studies on the health-effects recently.

I do it 4 days every now and then, it always gives me a good mood and focus both while doing it and in the days afterwards.

 

Real fasting (not the low calorie stuff that most people do when they say they are fasting) seems to ramp up the organelle production of antioxidants and other protective mechanisms to the point where actual chemotherapy becomes a lot more bearable. Might the the prudent thing to do for those of us who experiment with various chemicals that we hope are good but which might be harmful in some way

Edited by Cosmicalstorm, 07 May 2015 - 09:47 AM.

[lostfalco]

I have not been able to read the thread in it's entirety Falco, but if you like ketones, have you tried "real" fasting?

Hey Cosmicalstorm, I have tried the real thing...but never the synthetic thing. Thought it would interesting to compare the difference. =)

[BigPapaChakra]

I've tried KetoForce, but was experimenting with a high carb diet when I did so, and couldn't measure the results as well as I would have wished, but it did offer a nice little cognitive boost even then; kind of similar to bulletproof coffee. I'd suspect on a ketogenic diet, or, at least a high fat diet, the effects would be more pronounced because it would produce near starvation-like levels of ketosis if one were already producing them endogenously, too.

 

There is also this site that has the more "obscure" ketone esters used in studies: http://www.ketoresea...gory-s/1817.htm

 

I believe Dr. Peter Attia and Dr. D'Agostino have used the above site, but don't quote me on that

 

(The above site also has true ketone *esters*, whereas KetoForce and KetoCanna are keto-salts. Esters = much more powerful, but also MUCH more expensive)

Edited by BigPapaChakra, 07 May 2015 - 01:33 PM.

[lostfalco]

I've tried KetoForce, but was experimenting with a high carb diet when I did so, and couldn't measure the results as well as I would have wished, but it did offer a nice little cognitive boost even then; kind of similar to bulletproof coffee. I'd suspect on a ketogenic diet, or, at least a high fat diet, the effects would be more pronounced because it would produce near starvation-like levels of ketosis if one were already producing them endogenously, too.

 

There is also this site that has the more "obscure" ketone esters used in studies: http://www.ketoresea...gory-s/1817.htm

 

I believe Dr. Peter Attia and Dr. D'Agostino have used the above site, but don't quote me on that

 

(The above site also has true ketone *esters*, whereas KetoForce and KetoCanna are keto-salts. Esters = much more powerful, but also MUCH more expensive)

Very cool! Thanks for the info Papa. I've been messing around with caprylic acid and mct oil again recently so it'll be interesting to see how they compare to the BHB. Have you heard anyone talk about BHB as a signaling molecule/HDACi? This is the first I've heard of it. 

 

If you don't mind me asking...what experiments are you focused on right now? Anything stand out lately?

[Jochen]

 

 

If you don't mind me asking...what experiments are you focused on right now? Anything stand out lately?

 

 

I bet BPC, is mainly hacking his wife's sleep as well as his own :-)

[BigPapaChakra]

 

I've tried KetoForce, but was experimenting with a high carb diet when I did so, and couldn't measure the results as well as I would have wished, but it did offer a nice little cognitive boost even then; kind of similar to bulletproof coffee. I'd suspect on a ketogenic diet, or, at least a high fat diet, the effects would be more pronounced because it would produce near starvation-like levels of ketosis if one were already producing them endogenously, too.

 

There is also this site that has the more "obscure" ketone esters used in studies: http://www.ketoresea...gory-s/1817.htm

 

I believe Dr. Peter Attia and Dr. D'Agostino have used the above site, but don't quote me on that

 

(The above site also has true ketone *esters*, whereas KetoForce and KetoCanna are keto-salts. Esters = much more powerful, but also MUCH more expensive)

Very cool! Thanks for the info Papa. I've been messing around with caprylic acid and mct oil again recently so it'll be interesting to see how they compare to the BHB. Have you heard anyone talk about BHB as a signaling molecule/HDACi? This is the first I've heard of it. 

 

If you don't mind me asking...what experiments are you focused on right now? Anything stand out lately?

 

http://caloriesprope...ng-metabolites/

 

I'm about to start experimenting with a variety of things, but am not yet sure how to quantify things in a manner similar to Gwern. I was thinking about using very frequent blood ketone, blood glucose, heart rate variability, heart rate, oxygen content of body, body temperature, etc. to quantify things, in addition to subjective effects and before/after labs, but I'm not sure yet. In no particular order, these are things I'll be experimenting with very soon:

 

- Spectrometry kit to assess wavelengths of light in different indoor light sources, namely, CFLs, LEDs, 120 volt incandescents, and 130 volt incandescents. Looking to decrease blue, green, etc as much as possible, but get as much red, infrared, orange, and so forth. 

- Mammalian Dive Reflex - face dunks? swimming + breath holding? Not sure how I will accomplish it, but going to dig into it a bit more.

- Full blown cold adaptation

- CryoHelmet

- Water Filtered infrared-a radiation, as I posted about before (probably with the light source I find that has the least blue and most red, likely filtered through water with red dye)

- Ecopsychology/Environmental Medicine practices, especially using biodynamic-organic gardening outdoors in the sun  

 

 

 

If you don't mind me asking...what experiments are you focused on right now? Anything stand out lately?

 

 

I bet BPC, is mainly hacking his wife's sleep as well as his own :-)

 

Haha, fortunately our daughter sleeps through the night, so we're blessed/lucky in that sense. I am doing some sleep hacking though!

[Kalliste]

 

I have not been able to read the thread in it's entirety Falco, but if you like ketones, have you tried "real" fasting?

Hey Cosmicalstorm, I have tried the real thing...but never the synthetic thing. Thought it would interesting to compare the difference. =)

 

 

Please report the results! After fasting I always feel good for a few days.

[Jochen]

 

- Full blown cold adaptation

- CryoHelmet

 

 

I bet BPC, is mainly hacking his wife's sleep as well as his own :-)

 

Haha, fortunately our daughter sleeps through the night, so we're blessed/lucky in that sense. I am doing some sleep hacking though!

 

 

glad to hear about the daughter :-). My son still doesn't sleep through the night, but it's not much of a hassle for us with all our biohacking.

 

On your cold adaptation. I am doing the Wim Hof Method thing and so far so good. It's actually quite fun. Not at the part of the icebaths yet (10 minute cold showers is where I am at).

 

Can you tell a bit more about the cryohelmet?

 

the latest fad in sf is apparently http://www.cryohealthcare.com/. Got this through a Tim Ferris podcast.

[Kalliste]

I take a lot of cold showers. I have become addicted to them. I always feel great stepping out of one that last 3-5 minutes and then take a big cup of coffe. Great way to wake up. It gets better once you get used to it.

I want one of these Elastogel helmets, maybe the gloves too. But they are expensive

 

http://www.amazon.co.../dp/B00KQACDMW/

Edited by Cosmicalstorm, 09 May 2015 - 07:46 PM.