Is IP6 something that's sold by that name?
IP6 is inositol hexaphosphate. It is sold as IP6 or inositol hexaphosphate.
Also known as phytic acid. It'll prevent nutrient absorption so don't take it close to a meal or with mineral supplements.
Posted 21 September 2017 - 10:18 PM
Is IP6 something that's sold by that name?
IP6 is inositol hexaphosphate. It is sold as IP6 or inositol hexaphosphate.
Posted 22 September 2017 - 12:44 AM
I tried a subset of turnbuckle's updated protocol, but made some substitutions and omissions since it's all I have on hand until later this week:
Posted 22 September 2017 - 03:10 AM
Is IP6 something that's sold by that name?
IP6 is inositol hexaphosphate. It is sold as IP6 or inositol hexaphosphate.
Also known as phytic acid. It'll prevent nutrient absorption so don't take it close to a meal or with mineral supplements.
Ah really? Phytic acid is also cancer preventative and its nutrient absorption can be simply compensated for or countered.
I tried a subset of turnbuckle's updated protocol, but made some substitutions and omissions since it's all I have on hand until later this week:
nicotinamide — 1.5gtryptophan — 1gribose — 5gastragalus root extract (AMPK activator): 1-1.5 teaspoonsSome brain fog mornings for the 1st two days due to the tryptophan, which is not present when I cut back to 500 mg.Result: nice and easily noticeable improvements on the treadmill. Very solid feeling, and about 5 bpm lower heart rate than an earlier exercise session at the same workout level. I have a long run scheduled for Saturday, where I should really be able to put it to the test.
So ampk activators are fission side not fusion side? Doesn't that prevent taking metformin every day with this protocol?
Edited by Nate-2004, 22 September 2017 - 03:11 AM.
Posted 22 September 2017 - 06:11 PM
Update on my 4rd round of fission/fusion with NR instead of N+R.
I've been refining it as I go but I have definitely experienced similar responses to the fission side as far as the weakness and exhaustion level during and post workout that others have reported. Because NR takes longer I take it 4 hrs prior which is fine, I'm still at work and I don't mind waiting.
However, yesterday I took more NR than I did on Sunday, before and after the workout, while I experienced the same level of exhaustion that others experienced, I also experienced the inability to get to sleep as quickly last night. I felt too wired and this is despite the fact that I drank less coffee than usual during the earlier part of the day. I was actually trying to go without my usual dose of melatonin 45 mins before bed, that may have something to do with it. I don't know what the verdict on regular melatonin use but I keep hearing a lot of pros followed by cons followed by yet more pros. I don't know if I'll try the same level of NR next round of fission but we'll see.
Has anyone else experienced this? Could it have been the fact that I left out melatonin?
Edited by Nate-2004, 22 September 2017 - 06:11 PM.
Posted 22 September 2017 - 06:28 PM
Update on my 4rd round of fission/fusion with NR instead of N+R.
I've been refining it as I go but I have definitely experienced similar responses to the fission side as far as the weakness and exhaustion level during and post workout that others have reported. Because NR takes longer I take it 4 hrs prior which is fine, I'm still at work and I don't mind waiting.
However, yesterday I took more NR than I did on Sunday, before and after the workout, while I experienced the same level of exhaustion that others experienced, I also experienced the inability to get to sleep as quickly last night. I felt too wired and this is despite the fact that I drank less coffee than usual during the earlier part of the day. I was actually trying to go without my usual dose of melatonin 45 mins before bed, that may have something to do with it. I don't know what the verdict on regular melatonin use but I keep hearing a lot of pros followed by cons followed by yet more pros. I don't know if I'll try the same level of NR next round of fission but we'll see.
Has anyone else experienced this? Could it have been the fact that I left out melatonin?
I've had trouble getting to sleep on increased NR dosage.
I also used to take melatonin, but often didn't help.
Since I read Micheals supplement guide and started taking tryptophan (with NAM) 1 hour before bed, getting to sleep has been no problem.
Posted 22 September 2017 - 06:33 PM
Posted 22 September 2017 - 06:59 PM
Edited by MikeDC, 22 September 2017 - 07:00 PM.
Posted 23 September 2017 - 02:41 PM
Leucine for biogenesis
Free amino acids are found in rat mitochondria in the following decreasing concentrations—
Leu 4.28
Ala 2.63
Lys 2.55
Phe 2.07
Ile 1.89
Ser 1.81
Val 1.48
Met 1.38
Thr 1.33
Arg 1.29
Tyr 1.28
Asn 1.23
Gly 1.23
Gln 1.21
Asp 1.00
His 0.67
Glu 0.34
Trp 0.29
Pro 0.21
Cys 0.08
https://www.ncbi.nlm...pubmed/18636966
Thus leucine seems of great importance, and appears to be exceptional for biogenesis—
Leucine (0.5 mM) increased mitochondrial mass by 30% and 53% in C2C12 myocytes and 3T3-L1 adipocytes, respectively . . . Leucine also stimulated mitochondrial biogenesis genes SIRT-1, PGC-1α and NRF-1 as well as mitochondrial component genes UCP3, COX, and NADH expression by 3–5 fold in C2C12 cells.
https://www.ncbi.nlm...les/PMC2701939/
And—
Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice Addition of leucine to HFD correlated with increased expression of SIRT1 and NAMPT (nicotinamide phosphoribosyltransferase) as well as higher intracellular NAD+ levels . . .
https://www.ncbi.nlm...les/PMC3517633/
I don’t know how biogenesis will work with fission/mitophagy, but I will give it a shot.
Posted 23 September 2017 - 03:26 PM
Leucine for biogenesis
Free amino acids are found in rat mitochondria in the following decreasing concentrations—
Leu 4.28
Ala 2.63
Lys 2.55
Phe 2.07
Ile 1.89
Ser 1.81
Val 1.48
Met 1.38
Thr 1.33
Arg 1.29
Tyr 1.28
Asn 1.23
Gly 1.23
Gln 1.21
Asp 1.00
His 0.67
Glu 0.34
Trp 0.29
Pro 0.21
Cys 0.08
https://www.ncbi.nlm...pubmed/18636966
Thus leucine seems of great importance, and appears to be exceptional for biogenesis—
Leucine (0.5 mM) increased mitochondrial mass by 30% and 53% in C2C12 myocytes and 3T3-L1 adipocytes, respectively . . . Leucine also stimulated mitochondrial biogenesis genes SIRT-1, PGC-1α and NRF-1 as well as mitochondrial component genes UCP3, COX, and NADH expression by 3–5 fold in C2C12 cells.
https://www.ncbi.nlm...les/PMC2701939/
And—
Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice Addition of leucine to HFD correlated with increased expression of SIRT1 and NAMPT (nicotinamide phosphoribosyltransferase) as well as higher intracellular NAD+ levels . . .
https://www.ncbi.nlm...les/PMC3517633/
I don’t know how biogenesis will work with fission/mitophagy, but I will give it a shot.
Interesting. Some other quotes on stimulating ampk, NAMPT, Sirt1, and increased NAD+.
"Addition of leucine to HFD restored NAMPT expression (Fig. 2C). In addition, increased NAD+/NADH ratio was observed"
"dietary leucine stimulates SIRT1 signaling through activation of AMPK"
"leucine exhibited increases in expression of SIRT1 and NAMPT as well as intracellular NAD+ levels"
Posted 24 September 2017 - 02:52 PM
So biogenesis is just after fission? I wish I could search individual threads.
EDIT: I searched through where I could and gathered that exercise promotes biogenesis but not sure at what point, during or after and if both how long after. I gather hours or days?
Edited by Nate-2004, 24 September 2017 - 03:15 PM.
Posted 24 September 2017 - 03:18 PM
Interesting. Some other quotes on stimulating ampk, NAMPT, Sirt1, and increased NAD+.
"Addition of leucine to HFD restored NAMPT expression (Fig. 2C). In addition, increased NAD+/NADH ratio was observed"
"dietary leucine stimulates SIRT1 signaling through activation of AMPK"
"leucine exhibited increases in expression of SIRT1 and NAMPT as well as intracellular NAD+ levels"
Leucine is also the strongest activator of mTORC1 from what I understand, which prevents autophagy. Seems paradoxical to me but I'm not understanding everything fully just yet.
Edited by Nate-2004, 24 September 2017 - 03:19 PM.
Posted 25 September 2017 - 06:10 PM
I'm on a fission day today, while fasting (23 hrs so far) my way into ketosis so I can start the keto diet.
Do minerals like magnesium have any effect on fission or fusion? Supposed to get plenty of magnesium and potassium while in keto.
Here is what I found: https://www.ncbi.nlm...les/PMC4960558/
Cellular energy production processes are composed of many Mg2+ dependent enzymatic reactions. In fact, dysregulation of Mg2+ homeostasis is involved in various cellular malfunctions and diseases. Recently, mitochondria, energy-producing organelles, have been known as major intracellular Mg2+ stores. Several biological stimuli alter mitochondrial Mg2+ concentration by intracellular redistribution. However, in living cells, whether mitochondrial Mg2+ alteration affect cellular energy metabolism remains unclear. Mg2+ transporter of mitochondrial inner membrane MRS2 is an essential component of mitochondrial Mg2+ uptake system. Here, we comprehensively analyzed intracellular Mg2+ levels and energy metabolism in Mrs2 knockdown (KD) cells using fluorescence imaging and metabolome analysis. Dysregulation of mitochondrial Mg2+ homeostasis disrupted ATP production via shift of mitochondrial energy metabolism and morphology. Moreover, Mrs2 KD sensitized cellular tolerance against cellular stress. These results indicate regulation of mitochondrial Mg2+ via MRS2 critically decides cellular energy status and cell vulnerability via regulation of mitochondrial Mg2+ level in response to physiological stimuli.
Update on the tremor. I had to replace my tremor app with another one but the new one has the same numbers. Yesterday was the lowest I've ever seen the g forces go on the tremor test. Keep in mind it's usually around 100 and near or over 200 sometimes after a workout or in the morning. However, I've never seen it go below 30. Yesterday it got down below 10. This is promising. I can't definitively attribute this to the protocol we're doing here because I've also been eating fewer carbs over the past several days, which means it could be gluten or it could be something else. I haven't had any propranolol since early Saturday for an audition. I won't need to be taking that again for a while. This is encouraging that I'm doing something right, since this is the first time I've ever seen it objectively measured so low even after alcohol or propranolol or a combination of the two. I tested it twice to be sure.
Edited by Nate-2004, 25 September 2017 - 06:15 PM.
Posted 25 September 2017 - 09:37 PM
Not trying to be rude to anyone with what im about to say. Not looking for a big argument. Now tgat ive prefaced this i will say screw NR and hard. F this David Sinclair. Chromadex can suck big root. You could come down with cancer and make it worse by increasing NAD+. Lets move on to something else.
I hear your frustration but would you elaborate what triggered it?
Posted 25 September 2017 - 10:10 PM
Not trying to be rude to anyone with what im about to say. Not looking for a big argument. Now tgat ive prefaced this i will say screw NR and hard. F this David Sinclair. Chromadex can suck big root. You could come down with cancer and make it worse by increasing NAD+. Lets move on to something else.
I hear your frustration but would you elaborate what triggered it?
Posted 25 September 2017 - 10:45 PM
His father had recently died:
"You know it. Im in a foul mood today. My dad died and i come on here and I see this same BS."
See this thread
Posted 25 September 2017 - 10:48 PM
Posted 25 September 2017 - 11:31 PM
Posted 25 September 2017 - 11:42 PM
Nope, Ive got some really big ones over here. How about you crawl back into that hole you came from and stay away from everyone. Ive been looking for real hard studies showing some quality results from NR usage. Ive come up with nothing new that is of any real use. In theory, increasing NAD+ sounds good but, how long do these levels stay high and what real world benefits are anyone seeing on energy or slowing aging. Feel free to read reviews on Amazon for NR. This means all reviews including the 1 star reviews. Lets see some real irrefutable evidence showing that NR does much of anything in humans. Thats humans and not mice or rats.
Im interested in what shows true promise. So far this appears to be Rapamycin, Beta Lapachone, FOX04, and anything decreasing scenesent cells such as Dasatanib, or a significant decrease in inflammation.
Edited by Valijon, 26 September 2017 - 12:07 AM.
Posted 26 September 2017 - 12:06 AM
Posted 26 September 2017 - 12:12 AM
You don't know anything about NR. Keep pushing Rapamycin. Has your balls shrunk yet?
It's bad enough I have to suffer through trolls elsewhere on the internet.
I'm sure that MikeDC is delighted at his ability to disrupt discussions, but this makes Longecity an uncomfortable place to be.
Will some moderators please ban this guy from the forum?
Posted 26 September 2017 - 12:12 AM
Why are you so worried about my balls? I don't have an inflamed prostate,maybe you do? I did lose some fat recently through a combination of increased cardiovascular exercise along with the use of compound movements with heavy weights. Along with a total decrease in calories and carbohydrates. When I try some rapamycin, Ill be sure to share my experiences with everyone on here. You should ask some of the members who have tried something like rapamycin or read their public logs if these exist.
Posted 26 September 2017 - 12:27 AM
Hey, can you boys take this stupid argument elsewhere?
Posted 26 September 2017 - 01:00 AM
Steering this back to the original point of all this:
Small mitochondria are less efficient and any problem with the mtDNA genes can be detected by the cell via the membrane potential, which marks the mitochondrion for mitophagy. Thus pushing the balance of fission and fusion in the direction of fission can clean up the population of mitochondria, and can be also used for enhancing exercise.
Large mitochondria are more efficient. I’ve notice that using supplements that push mitochondria to smaller size don't work well with C60 (and in fact can be terrible) thus I wondered if pushing it in the other direction might make C60 more effective. I’ve tried this a few times, using C60 (in MCT oil: 1-2 mg C60 and a like amount of hydroxytyrosol), and it does seem to be more effective when combined with several grams of stearic acid. At least, I’m seeing hair regrowth that I haven’t seen since I first tried C60 in olive oil five years ago.
They more I go back through this thread and re-read it the more I see that we're really refining an evolving protocol. The promising results I'm seeing with my tremor says not only a lot about doing this but it potentially confirms that ET could be the result of mitochondrial dysfunction. I think for me what all this boils down to a process of artificial selection. We're taking a generation of mitochondria, applying stress, and then promoting growth when the weak have died off. It's like breeding only the largest, juiciest tomatoes. Mitogenesis is something I'd be interested in understanding more about. I'll be (re)reading and trying to understand the original link to the mechanisms of fission and fusion but there's also the biogenesis part that I don't understand at all.
Edited by Nate-2004, 26 September 2017 - 01:14 AM.
Posted 26 September 2017 - 01:47 AM
Posted 26 September 2017 - 01:59 AM
Could someone share the latest protocol with me?
My current routine -- when life doesn't get in the way -- is beginning a fast at about 10PM at night, fasting all night, taking NR/R-ALA/Ubiquinol first thing in the morning, fasting at least 16 hours (today I did twenty hours), and then feasting like crazy a couple hours before my fast is to begin again.
I'm hoping that autophagy is happening like crazy during the day while I'm fasting (along with more human growth hormone being produced) which will promote fission and then when I eat the remaining mitochondria will start to undergo fusion.
Since the weather is improving here, I hope to incorporate some pre-fast breaking running into my routine to really push the autophagy to the max right before feasting.
Posted 26 September 2017 - 03:07 AM
Ubiquinol and R-ALA should be left out of fission. Take those during fusion. Here is mine:
Fission:
Fasting optional
1000mg NR 4 hours prior to a HIIT workout
Take nothing else as far as supplements till the following day (thinking of extending another day)
Fusion:
2 days of:
Hydrolyzed Collagen Powder in the morning
Stearic Acid 10g twice daily
30mg Sulforaphane in the afternoon together with:
PQQ
1 Tbsp EVOO
1 Tbsp Flaxseed Oil
Ascorbic Acid
Viva Fish Oil and Krill Oil with Astaxanthin
Curcumin
Sometimes Rosmarinic Acid
Garlic Extract
Sometimes Gamma/Alpha E and tocotrienols
all with This Smoothie #2
Back to fission.
My only concern is that on a high fat low carb diet I'm probably going to end up getting stearic acid from all the food on fission days. What to eat on fission days is definitely something I need to figure out. That smoothie has a lot of antioxidants which may not be good during fission. I could just try to fast mostly but that's tough to do more than once a week.
Edited by Nate-2004, 26 September 2017 - 03:13 AM.
Posted 26 September 2017 - 09:23 AM
My only concern is that on a high fat low carb diet I'm probably going to end up getting stearic acid from all the food on fission days. What to eat on fission days is definitely something I need to figure out. That smoothie has a lot of antioxidants which may not be good during fission. I could just try to fast mostly but that's tough to do more than once a week.
I would not bother with it as it could be the exact opposite. Overall connection between dietary fat intake and blood levels are quite complex as liver quickly suck all dietary nutrients trough portal vein and actual blood levels depend more on internal production.
"– Eating less carbohydrate will make less saturated fat appear in your blood between meals, even if you do eat more saturated fat, and this is most true for the lauric acid and myristic acid in your diet."
https://profgrant.co...-low-carb-diet/
Posted 26 September 2017 - 10:04 AM
They more I go back through this thread and re-read it the more I see that we're really refining an evolving protocol. The promising results I'm seeing with my tremor says not only a lot about doing this but it potentially confirms that ET could be the result of mitochondrial dysfunction. I think for me what all this boils down to a process of artificial selection. We're taking a generation of mitochondria, applying stress, and then promoting growth when the weak have died off. It's like breeding only the largest, juiciest tomatoes. Mitogenesis is something I'd be interested in understanding more about. I'll be (re)reading and trying to understand the original link to the mechanisms of fission and fusion but there's also the biogenesis part that I don't understand at all.
Exactly. I posted the following on the ancestor thread to this one, comparing this process to breeding--
One can think of mitochondria as sheep on a farm (or bacteria in a vat), with each cell/farm having a herd of a thousand or so. Thus to maintain the best herd, sheep must be encouraged to breed, sick sheep must be culled, and the herd must be fed a nutritious diet. One could do all those things at once and all the time and end up with a herd that is far from optimal. For instance, look at the culling aspect. If all sheep act equally healthy from a diet rich in antioxidants and with ATP production jacked up by C60, then how does the cellular machinery know which ones to cull? So withholding supplements that can boost mito function before taking mitophagy boosting supplements would appear to make sense.It's also true that larger mitochondria are more efficient for day to day use, but must be fissioned into smaller bodies for quality control and culling, so these are contradictory requirements.
Posted 26 September 2017 - 10:36 AM
Leucine for biogenesis
Free amino acids are found in rat mitochondria in the following decreasing concentrations—
Leu 4.28
Ala 2.63
Lys 2.55
Phe 2.07
Ile 1.89
Ser 1.81
Val 1.48
Met 1.38
Thr 1.33
Arg 1.29
Tyr 1.28
Asn 1.23
Gly 1.23
Gln 1.21
Asp 1.00
His 0.67
Glu 0.34
Trp 0.29
Pro 0.21
Cys 0.08
https://www.ncbi.nlm...pubmed/18636966
Thus leucine seems of great importance, and appears to be exceptional for biogenesis—
Leucine (0.5 mM) increased mitochondrial mass by 30% and 53% in C2C12 myocytes and 3T3-L1 adipocytes, respectively . . . Leucine also stimulated mitochondrial biogenesis genes SIRT-1, PGC-1α and NRF-1 as well as mitochondrial component genes UCP3, COX, and NADH expression by 3–5 fold in C2C12 cells.
https://www.ncbi.nlm...les/PMC2701939/
And—
Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice Addition of leucine to HFD correlated with increased expression of SIRT1 and NAMPT (nicotinamide phosphoribosyltransferase) as well as higher intracellular NAD+ levels . . .
https://www.ncbi.nlm...les/PMC3517633/
I don’t know how biogenesis will work with fission/mitophagy, but I will give it a shot.
It seems leucine has to be spaced off from Tryptophan intake (if the Tryptophan is for boosting NAD+ in the brain, which is what I remember), as it will diminish Tryptophan uptake into the brain. It also activates liver TDO, resulting in more Tryptophan being metabolized peripherally.
https://www.ncbi.nlm...les/PMC4259507/
Haven't found if LEU does work to activate IDO, too. If so, it could be an interesting option to preload it some time before taking Tryptophan...
Posted 26 September 2017 - 11:21 AM
Two-path NAD+ daily protocol (experimental, updated)
Fission/mitophagy (before bed)
Nicotinamide (NAD) — 1.5g
Tryptophan (NAD) — 1g
Ribose (NAD) — 3g
AMPK activators (Life Extension) — 1g
Fisetin (Sirt1 activator) — 100mg
Fusion/Biogenesis (12 hours later)
Broccoli sprout extract with sulforaphane* (fusion) — .5-1g
Leucine (biogenesis) — 5g
PQQ (biogenesis) — 20mg
Hydroxytyrosol (biogenesis & antioxidant) — 25mg
Vitamin B complex (commercial mix)
*Stearic acid appears better for fusion, but its half-life of 17 hours is too long for daily cycling of the protocol. Sulforaphane’s half-life, by contrast, is a reported 2-3 hours.
Notes:
1. AMPK activators — See Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy. In addition, it appears that the advantages of spermidine derive at least in part from its activation of AMPK — Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway. Spermidine is difficult to find so I haven’t included it in the protocol.
2. Sirt1 activator — See Nicotinamide-induced mitophagy: event mediated by high NAD+/NADH ratio and SIRT1 protein activation.
3. B vitamins — Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism. It's possible that B vitamins might go better with fission, and perhaps with both. In any case, I'm not using a lot.
4. For use with exercise, the above fission protocol can be used (without the tryptophan, or optionally replaced with half a gram of niacin) an hour or so before going to the gym. Fission of mitochondria renders them less efficient at producing ATP and allows one to exercise with reduced weight while getting more muscle credit for it. (This assertion is based only on my own experience.) See also Exercise Like a Girl.
5. Nicotinamide is the same as niacinamide, while nicotinic acid is the same as niacin.
Edited by Turnbuckle, 26 September 2017 - 12:14 PM.
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