One column is the effects on lifespan by decreasing the amino acid and another column is for increasing the amino acid.

Assuming what you said 3000mg ever 12 hours. Let’s say the half life is 2 hours. After 12 hours, 3000mg is just under 50mg.

Now if you break up the cycle into 3x. Every 8 hours, you only need 1000mg to have a better effect than 3000mg every 12 hours.

Or by taking slow release vitamin C I can ensure that probably get away with 2 x 800mg a day with higher minimum vitamin c in the system.
I will also reduce the amount of work my system have to remove the excess.

What do you think of this idea?

I will stick with what works for me. For whatever reason for it to be antiviral there need to be high amounts of both these two substances in the blood. I know they say that your body will pee out any amount over 500mg or so, but I’ve tried and tested it to not be true. If my body peed it out why then a 3000mg dose x3 per day will totally diminish the symptoms while a 1000mg X3 did NOT have such an effect.

Clearly as this doctor states it needs to be in very high amounts 2 to 3 times daily to have an effect. for anyone that thinks this is BS it’s all good but it is very easy to test. Next time you catch a cold (and I know for a fact that all you will catch one nananana) just try 3000mg X3 of vitc and same Lysine and would be nice to come in this forum and describe the results, good or bad I’d love to know.

So again for me I’ve found what works to prevent colds two times daily morning and evening at 3000X2 (plus works best since i work) in the flu season then i taper it of to either 1X2000 or 2X2000. I’m not going to fix something that is not broken. But you can experiment and you’ll find out soon enough if it works for you.

2 Likes

Indeed! Vertical lines would have been useful IMO. Fixed my post.

2 Likes

I hear you but to what extend it affects the life span, and at what amounts? To say as an example that Lysine is negative for life extension it is ok, but every food out there including greens have lysine. In other words, if you’ll ever consume any protein, you will consume lysine. My point being if you say you consumed 3000mg of lysine through food anyway, maybe supplementing 4000mg more daily will not have any further effects. Same as let say you have 10 drinks and you are already drunk, one more drink will just be the same; you simply are still drunk. Clearly, not arguing but just pointing out that there’s got to be way more nuance to any study analyzing nutrients (any of them) and longevity in general, since they tend to appear on every food we consume.

Everything has it’s time and place. If you are sick, you may need high doses. If you aren’t sick, it might be better not to take it. Vitamin C seems to be good all around though. Lysine may be good or bad depending on the circumstances. I’m not an expert in this area, so I don’t think I can say any more than that.

2 Likes

_2021_AA_MEL_Guidelines.pdf (339.4 KB)

Here are Doris Loh’s Vit C recommendations for COVID / long COVID / maintenance. It also includes her melatonin recommendations for the same. She doesn’t recommend high doses all the time but only during infection

Update

Doris Loh’s 2023 guidelines
April_2023_Melatonin_Dosing_Schedule.pdf (146.7 KB)

5 Likes

The ‘high dose Taurine’-hype, based on very interesting but limited research, really surprises me. I know I keep repeating myself with that regard, but I’m just trying to understand.

Granted, this is a suggestion from Perplexity.ai including in vitro studies and under varying circumstances (such as kidney injury), but I’d love to understand if others are not concerned that in fact with high doses of Taurine one may counteract (some of) the effects of Rapamycin on mTOR-signaling.

Perplexity: " The search results provide mixed evidence regarding the dose-dependent effects of taurine on mTOR activation:

  1. Taurine in C2C12 Myoblast Cells:
  • In C2C12 myoblast cells, taurine dose-dependently promoted mTOR phosphorylation, with the best stimulatory effects at 120 μM. This suggests that even relatively low doses of taurine can activate mTOR in certain cell types 1.
  1. Taurine and Muscle Mass Restoration:
  1. Taurine in L6 Cells:
  1. Taurine and Kidney Injury:
  1. Taurine and Cancer Cell Protection:
  • Study: In ovarian cancer models, taurine supplementation was associated with activation of mTOR along with other signaling pathways.
  • Results: The study found that taurine elevated intracellular levels and activated mTOR/DNAPK/ATM/ATR pathways while also providing protective effects against DNA damage, indicating a complex relationship between taurine supplementation and mTOR activation in the context of cancer cell growth (https://www.biorxiv.org/content/10.1101/2023.02.24.529893v4.full).

These studies demonstrate that taurine can indeed activate mTOR, but they do not provide clear evidence that the high doses used in longevity studies necessarily led to significant mTOR activation. The effects appear to be cell-type specific and may vary depending on the physiological context. More research is needed to establish a clear dose-response relationship between taurine supplementation and mTOR activation in vivo, particularly at the doses used in longevity studies."

2 Likes

@约瑟夫_拉维尔 the melatonin dosage shown in the article is different to what I saw in the website. I thought it is much higher?

I must admit I am surprised that I missed that Doris Loh article. Anyway, as a general I prefer to take as little as possible of everything. I even believe that if we stay in a fasting state we probably need even less… maybe there is a suitable cycling to look into. I have no issues with taking more when needed, but how did the “high” dose justification comes about? Just the gut feel that something is off. I just had COVID last week from Wednesday night and only had a clear test on Sunday (no covid). The first 24-36 hours was unpleasant… almost impossible to sleep… and I was not happy. I must admit, that I took no more than 200mg of melatonin each day for the first 2-3 days and I totally forgot about the vitamin C. I was more concern about drinking lots of water.

Moving aside, is there a good way to test vitamin C level in our body? It has also come to my attention that I probably need vitamin B… since both B and C are water soluble, they are least likely to remain in our system for long. I noticed my heel has been cracking lately plus according to the DNA test … my body does not absorb the vitamin B properly.

As for iron level, according to the DNA my iron level is suppose to suffer (low absorption) however, my ferritin test shows that I am overloaded with iron… though only 1.5x more than the max, instead of the previous 2.5x.

Any thoughts? Thx :wink:

1 Like

@adriank I have been trying to interview Russell Reiter or Doris Loh. Doris has said yes so that may happen

According to Reiter, there is no dangerous dose of melatonin. He says it is an old chemical that our bodies (and is made by plants and animals) can use without overdosing.

He says he takes ~ 80mg at night (has taken as much as 200 mg per day). He takes melatonin during the day if sick. He regrets not starting taking mega doses earlier (started around 50?). He says we make less as we age and we need more as we age. And there is no danger so why not take a lot. It’s a good question.

The supplemental melatonin gets into all cells of the body but only the pineal gland melatonin gets into circulation. I think I’d like to get more melatonin into my brain cells and endothelial cells and more.

Apparently Doris does not agree with Reiter on dosing as she recommends (per her maintenance dose) much less when not sick.

I am working up the courage to start taking it before weight lifting just to see what happens.

4 Likes

Good luck. I have been a recent melatonin user. Normally each night I take 140mg to 160mg. I do hate taking so many small pills but sadly we can’t find bigger pills. I keep 240x20mg pills from iHerb. But as you can imagine, I can easily go through that in a month. I would not say I get sleepier with melatonin… I can fall asleep just by putting my head down normally.

I guess melatonin and vitamin B, C, D, K2 and lysine, taurine and magnesium made it to my regular supplement. I am reluctant to take calcium. I have MCT and hemp oil. I do not take fish oil anymore. There are a few others for considerations but I really do not like lots of pills.

2 Likes

I think you are saying you have 20mg pills. As a result of @约瑟夫_拉维尔 sharing Dr Loh’s protocol, I found 60mg pills from vitamatic to have on hand incase I should need the high dose.

I wound up choosing their sugar free gummies at 30mg per gummy with the thought that if I am sick, I won’t have it in me to take several pills every two hours.

1 Like

Interesting… I wonder if there are any issues shipping to Australia. Anyway it is still a lot cheaper for me to buy 20mg pills from iHerb. Vitamatic cost $25 usd for 60 x 60mg pills … so about 3.6g of melatonin. iherb cost me less than $15 usd for 240 x 20mg pills which is about 4.8g of melatonin. It gets expensive when you consume a lot.

1 Like

Worrying whether taurine or whatever substance “X” revs up mTOR, whilst rapamycin turns it down is classic mechanistic reasoning, no? I’m a very simple guy, so I like the black box approach. You have inputs into the black box, something happens inside the black box, and then you have outputs at the other end. Taurine, substance “X”, rapamycin etc. are the inputs. By definition in this scenario, we don’t know what happens inside the black box. We can only observe the output - here, outcome studies measuring whatever the marker, perhaps all cause mortality, some morbididy outcome etc.

Now, if I find that input of taurine into the black box results in an output that has as an outcome longer lifespan/healthspan, I’m satisfied. Now that’s mice - ignorable. But we have human studies that show various good outcomes - lowers BP, helps in heart health (albeit in heart failure), exercise and various other measures. So the positives are there, even if the most dramatic (lifespan) are not provable in humans. OK, what about the negatives - I’ve looked for them, not found them. I looked for interactions with drugs/supplements I take - nothing. So, being the simple guy that I am, I go ahead and take taurine, although only in doses that have shown some clinical effect 2-4g a day (1.6g/day was shown to lower BP, which is slightly elevated for me). It seems studies show that up to 6mg/day is safe.

Now, asking about taurine countering rapa, is asking about what happens inside the black box. By definition we don’t know - because we don’t have a perfect model of how the human body works, we can only speculate. I am happy to speculate just as lustily as the next guy, and read with pleasure the various papers on pubmed, but at the end of the day, it’s speculation. Outcomes trump it every time.

Yet, since we all have to make decisions, we need some kind of reasoning chain. Yours may be better than mine. Here’s mine:

1)There is no evidence that rapa works better in old mice, vs supplied all through life from young to old. In fact, we have experiements that the longer on rapa, the longer mice live. Including starting at a young age.

2)Taurine declines in mice with age. But it is higher in youth - yet rapa works in young mice, so it doesn’t seem that higher-taurine-young-mice don’t benefit from rapa. This suggest strongly to me, that if I have youthful levels of taurine thanks to supplementation, it will not prevent rapa from being beneficial - after all, if I started rapa at 20 with a high level of taurine, I’d still benefit from rapa, just as young mice do.

Of course, if rapa doesn’t benefit humans, then that’s a rapa problem and has nothing to do with taurine, so we can ignore that - it’s in the very assumption itself. We assume/hope/take a risk, that rapa works for us. I don’t see how taurine enters into it.

Now, one may ask “won’t it interfere with rapa, because mTOR” - you’re asking about what happens inside the black box - but I say, the outcome in young mice with high taurine is beneficial, so…

As long as we’re speculating, I can speculate as much as the next guy/gal. I speculate that rapa simply turns down the mTOR, so taurine is irrelevant in that case. It’s as if you rev up the engine with taurine which ordinarily will make you race down the street - but rapa puts the transmission in neutral - you can rev as much as you wish it won’t make any difference.

However, we are pulsing rapa. And we have seen in the PEARL trial, and anecdotal evidence (plus waiting on Brad Stanfields study), that muscles benefit on rapa - stronger. Here we see a perfect analogy.

Somone worries, but since muscles grow with mTOR activation, won’t rapa shrink your muscles? Mechanistic speculation about what happens inside the black box. Then we look at outcomes - the opposite seems to be true, muscles benefit from rapa. Lesson learned? Only outcomes matter. Worrying about the inside of the black box is of intellectual curiosity (which I share with gusto!), but for actionable pointers, I look to outcomes and try not to be guided by mechanistic speculation.

It’s all a gamble. It’s possible the opposite is true - rapa may inhibit whatever the benefits of taurine are, rather than taurine abolishing taurine benefits. I’m gambling that they’ll be additive. What’s the truth - we won’t know for now, or maybe ever. Speculatively, I turn again to mouse studies. High taurine in young mice is presumably good, and rapa in young mice is also good, so it doesn’t seem as if rapa demolishes the benefits of taurine. It looks like regardless of high (young mice) taurine status or low (old mice) taurine status, rapa is beneficial. It seems that if rapa doesn’t affect taurine, and taurine rapa, then perhaps one could stack the benefts of both. Same way exercise is good for muscles, and it looks like rapa is good for muscles so one does not abolish the other, as muscles benefit from both. It’s not “exercise alone = muscle benefits” and “rapa alone = muscle benefits” - it’s “exercise AND rapa = muscle benefits” That’s my roll of the dice with taurine - they’ll stack positively.

Now, since we pulse rapamycin, my plan is (I start rapa in January), to not supplement with taurine on the day of rapa and the following day, since anecdotal evidence with exercise seems to be that more folks report better resuts with not exercising on those two days. Of course, my reasoning might be all wrong, but being a simple man I must rely on my own meager resources, and I admire those who can figure it out better. YMMV.

3 Likes

Yes - not good for longevity if taken frequently:

“It’s interesting and encouraging to think a dietary change could still make such a big difference in lifespan and what we call ‘healthspan,’ even when it started closer to mid-life.”

Restricting dietary isoleucine increased the lifespan and healthspan of the mice, reduced their frailty, and promoted leanness and glycemic control. Male mice had their lifespans increased 33 percent compared to those whose isoleucine was not restricted, and females had a 7 percent increase.

These mice also scored better in 26 measures of health, including muscle strength, endurance, blood sugar levels, tail use, and hair loss.

The male mice in this group had less age-related prostate enlargement, and were less likely to develop the cancerous tumors that are common in the diverse mice strains.

2 Likes

So it appears that whey protein, which is high in isoleucine, would be bad for longevity. This goes in contradiction to many health influencers on the internet.

However, I trust science more than longevity influencers, so a whey protein (or any protein) supplement is probably not for me. :frowning:

I guess I’m not going to be a body building bro anytime soon. :stuck_out_tongue:

1 Like

Maybe we should stop consuming protein completely and then just supplement with the aminos that result in longevity. I don’t even know if that is possible or which kinds of food would have no protein/aminos unless we only eat sugar and butter LOL. But you guys have at least convinced me to taper Lysine off a bit and only use it when start feeling any symptoms of getting a cold.

I wonder though how come B Johnson is still taking about 2000mg of Lysine daily? I have to assume with his entourage of doctors and limitless resources he must know it is good to take.

1 Like

Thanks this is interesting reasoning. Trying to compensate the decline in taurine levels with age doesn’t sound unreasonable indeed. But wouldn’t that imply taking an estimated 1-2 grams/day at age ~40; ~2-3 grams/day at age ~50, ~ 3-4 grams/day at age ~60. I commonly saw suggestions to take >6-8 grams/day even at (relatively) younger ages.

Perhaps I’m overthinking this, and/or approaching this with a too broad generalisation - a while back while striving to maintain a CRON diet, I took a range of supplements each day that gave positive health outcomes in studies, including selenium. This is only but an example of a study that made me reconsider: Selenium Deficiency Is Associated with Pro-longevity Mechanisms. And there were multiple of such studies that made me pause and wonder whether I was not actually compromising potential health benefits I was aiming for with among others CRON/Rapa, by taking certain supplements.

(Actually I do supplement Taurine also, but mostly since I eat a vegan diet, and currently I take at most 1g/day. I may reconsider in the future/once I reach a more advanced age).

1 Like

I’m sticking with clinically proven - or studied - dosages of taurine, regardless of age. However, I’m 66, so in my case, the 2-4g/day. It’s possible that more would be better as I get older, but since there is no clinical data, I’m staying put unless the science says otherwise in the future.

Regarding CRON - please be aware of the danger of bringing up CR with me, because I’m liable to get even more wordy than usual :rofl: I’ve been studying, discussing and thinking about CR for decades and practiced it myself for many years.

Back in the day, on the CR email list (even before the website) there was always a discussion of whether supplementing on CR made sense. In general, even beyond the supplementation issue, we have to acknowledge that the CR organism is rather different from the ad-lib one. So even if some supplement or other shows positive effects in ad-lib people (say, higher doses of vit. B2 for brain health), that may be a compensatory measure to the ravages of an ad-lib diet. Similar to how a pillow tied to the head (extra B2) is very useful if you are in an environement of regular hammer hits to the head (ad-lib), but is completely useless if not counterproductive in an CR’s individual. This extends to everything - medications included. Just because it is good for the ad-lib crowd doesn’t mean it’s good for the CR crowd - and most studies are done in the ad-lib crowd. It’s somewhat similar to the situation on rapamycin.news, where we discuss medicaitons which have been studied in disease states, and are of unknown effect in healthy individuals - we are left speculating, extrapolating and generally hope-healthing.

But getting back to abolishing/diminishing the benefits of CR with supplementation, we do know of one extreme - malnourished. Here low calories combined with a very nutritionally deprived food results in negative effects - see starvation anywhere, recently Africa, not healthy. By the way it’s less clear on an epidemiological level if undernutrition is also bad in the context of perhaps an unbalanced dietary components - we’ve seen evidence in many countries during war or times of economic hardship, where there was undernutrition but not starvation that generally the health effects were actually positive(!).

That brings us closer to the issue of CR. There is a concept of DR, where the distinction is that in animal experiments, with DR (dietary restriction), you simply cut down on the food, and CR where you cut down on the calories, but boost the nutrients to keep at normal levels. In other words, with CR, the idea was to isolate the calories themselves, whereas with DR, you cut back on the whole shebang. From an evolutionary point of view, DR is what animals actually evolved with. A mouse out in the wild, has less food and all its components, it’s not that it’s just short on energy, but magically has all the micronutrients supplied.

So the question is, does supplemented CR abolish the benefits of DR. Well, it’s not so simple to say, well, of course, go for DR - because remember, there is the malnutrition model of starvation. So there is something to the “ON” part of CRON. How to distinguish what to supplement with? My own speculation follows - and caveat, it’s your classic mechanistic reasoning, as the studies are lacking, so take it with that in mind.

I figure that it’s all about signalling. In order to kick in defensive CR mechanisms, the organism must first recognize that it is in a situation of food shortage. How does it do that? This is the key question for me. If you run a computer simulation of a number of variables looking for how a given condition selects for one variable versus the other, it seems to me there similarly must be a way of teasing out the key variable in food signalling. So, how does a mouse physiology distinguish between a “fed” state vs an “unfed” state - the variable must be unique to each state. So, for example, you will almost never have a situation, where you are lacking food but somehow have plenty of methionine on hand - that is because to get appreciable amounts of methionine you must get it from appreciable amount of food. Thus, a high methionine signal has evolved to signal: “plenty of food, fed state!”. Meanwhile, for example, having plenty of water doesn’t give us a that same “plenty of food” state, because you can have plenty of water but still starve - so that signal didn’t evolve as unique.

I therefore take a similar approach. I look for those things which definitely signal “fed” state, or “unfed state”. So I avoid supplementing with an amino-acid like methionine, because it signals “fed” - and possibly that’s one reason why restricting methionine vs excess methionine is life-health extending. Branched chain amino-acids have a signalling function (f.ex. high isoleucine is health negative). And also that’s why I feel uneasy when artificially short-circuiting the hunger signal - it might turn down the CR response, because where in nature do you have a starving organism that feels no hunger - it seems hunger has strongly evolved and been preserved, because without being motivated to eat, an organism dies, period.

Therefore, as I approach my supplement cabinet, I ask myself looking at each supplement - which one is a unique signal that stimulates or tamps down on the CR beneficial effect. Many will be neutral, so I can take them, no issue. But some will be very unique, and those I need to pay attention to. Unfortunately, as is the case with most of physiology, we don’t have perfect data, so it’s an evolving space - we’re flying blind to some degree. I - total speculation here - do a little gedanke experiment for myself - as I hold up a supplement, I picture that mouse in a situation of little food, would this molecule be present or uniquely absent in this situation? And therefore send a signal “fed”, or “unfed”. And base my decision on that.

Again, a lot of this is frank speculation, but that’s my reasoning chain - signalling is important (as we’ve seen in those CR experiments where the mere smell of food abolished the CR effect, because where in nature would you have a smell of food but no food - and so we evolved to see the signal “food smell” as “fed”). If a mouse/fly/human can smell food, it can access it - no CR effect. No food, and no contrary signal that there is food, OK, now we kickstart the CR emergency procedures. I look at a supplement - what does it signal? YMMV.

3 Likes

An interesting take and approach. Personally I feel I’m constantly flying blind with this regard, repeatedly running into research after the fact. :neutral_face: I remember the protein (powder) discussions, of which plenty of suggestions seemed to conflict with for example Fontana’s research. Imho there’ve been plenty of such examples.

1 Like