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What's been the biggest revelation that's come out in the last five years with Supplements.

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#1 RichardAlan

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Posted 27 December 2018 - 04:30 AM


In other words what's the most important things you have come across that you know about now but didn't know about five years ago and have you made changes to what you are taking based on these new findings? 


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#2 Mind

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Posted 27 December 2018 - 06:39 PM

Senolytics, NAD+ boosting supps, MitoQ


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#3 brosci

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Posted 29 December 2018 - 08:21 AM

Senolytics, NAD+ boosting supps, MitoQ

 

What are your thoughts on the new LEF Senolytic formula?  They've got it marked as a once-weekly supplement.  I'm surprised they're looking at the 74mg of quercetin phytosome being taken this infrequently as having the desired impact.  Meanwhile, Thorne is pushing quercetin phytosome at 250mg and saying to take this 2x a day every day.

 

What other senolytics come to mind as far as nutritional supplements go (and not research pharma drugs) ?



#4 Mind

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Posted 29 December 2018 - 12:34 PM

If a senolytic therapy is "effective" and it wipes out most "bad" senescent cells in your body, then you should only need to take it once a year, or even once every several years. Senescent cell burden (the zombie cells, the bad ones) only grows very slowly throughout the course of a lifetime.

 

In addition, like everything related to metabolism, cell senescence is a complicated evolved program that plays multiple roles within the body. I would NOT want to continually suppress the process, for fear of significant side effects.

 

I am taking the LEF product right now, but only plan on taking it for a month, then maybe start it up again later next year, depending upon new research results and/or biomarker testing I might get done in the upcoming year.


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#5 RichardAlan

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Posted 29 December 2018 - 01:40 PM

What are your thoughts on the new LEF Senolytic formula?  They've got it marked as a once-weekly supplement.  I'm surprised they're looking at the 74mg of quercetin phytosome being taken this infrequently as having the desired impact.  Meanwhile, Thorne is pushing quercetin phytosome at 250mg and saying to take this 2x a day every day.

 

What other senolytics come to mind as far as nutritional supplements go (and not research pharma drugs) ?

 

What's the LEF Senolytic formula that you mention here? Also what gives you some confidence in that formula?



#6 Oakman

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Posted 29 December 2018 - 02:37 PM

1) Far and away, I would credit LongeCity.org as bringing to light research and anecdotal evidence on supplements in one place. Until I found this forum, as far as supplementation, I was flailing around in a sea of disinformation, unable to make heads or tails of what the true possibilities were. The forum has provided insight, information, and encouragement.

 

2) The potential of NAD precursors

3) The potential of senolytics.


Edited by Oakman, 29 December 2018 - 02:37 PM.

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#7 Mind

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Posted 29 December 2018 - 04:05 PM

What's the LEF Senolytic formula that you mention here? Also what gives you some confidence in that formula?

 

The "Senolytic Activator"

 

It has been known for a while that quercetin has some marginal senolytic activity....it has showed up in some research (but not all). LEF cobbled together a bunch of disparate research on quercetin and theaflavin and presented it in their most recent magazine. It seemed reasonable. Odds of negative side effects seems low (from natural compounds). I know a few of the people behind the products, so I trust them a bit more to produce something relatively good.

 

 


Edited by Mind, 29 December 2018 - 04:05 PM.


#8 John250

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Posted 29 December 2018 - 08:21 PM

Cycloastragenol

#9 RichardAlan

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Posted 30 December 2018 - 05:34 AM

Cycloastragenol

 

Tell us more and why do you feel this is the biggest thing?


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#10 John250

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Posted 31 December 2018 - 03:48 AM

Tell us more and why do you feel this is the biggest thing?


I don’t necessarily think it’s the biggest thing but it’s new and it’s immune boosting properties and telomere extension benefits seem pretty good.
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#11 smithx

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Posted 03 January 2019 - 08:34 PM

I stopped taking MitoQ after seeing this study:

 

The targeted anti‐oxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue

https://www.ncbi.nlm...les/PMC5880956/

 

What are your thoughts about it?

 

Senolytics, NAD+ boosting supps, MitoQ

 


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#12 Mind

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Posted 03 January 2019 - 10:00 PM

I stopped taking MitoQ after seeing this study:

 

The targeted anti‐oxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue

https://www.ncbi.nlm...les/PMC5880956/

 

What are your thoughts about it?

 

The study was in mice and opossum cells (in vitro). That doesn't mean it should be ignored. Of course not.

 

However, for being a relatively new supplement, it has already compiled a large volume of research, most of which does not indicate negative side effects. So far, the balance of research would seem to indicate that MitoQ is effective in slowing some aspects of aging. https://www.ncbi.nlm...d/?term="mitoq"   and https://www.mitoq.co...-collaborations


Edited by Mind, 03 January 2019 - 10:01 PM.

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#13 John250

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Posted 03 January 2019 - 10:46 PM

The study was in mice and opossum cells (in vitro). That doesn't mean it should be ignored. Of course not.

However, for being a relatively new supplement, it has already compiled a large volume of research, most of which does not indicate negative side effects. So far, the balance of research would seem to indicate that MitoQ is effective in slowing some aspects of aging. https://www.ncbi.nlm...d/?term="mitoq" and https://www.mitoq.co...-collaborations


Anyone know what the human equivalent dose would be? Most studies on animals use an astronomical amount of the compound.

#14 John250

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Posted 04 January 2019 - 01:30 AM

I believe it said the were given 500 nmol/L how would that be converted to mg?

#15 VP.

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Posted 04 January 2019 - 02:17 AM

Rapamycin. The promise of senolytics. 


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#16 smithx

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Posted 05 January 2019 - 12:51 AM

In that same study they tested SS-31 and found that it didn't cause problems. That compound also seems interesting:

https://www.ncbi.nlm...les/PMC4921212/

 

The study was in mice and opossum cells (in vitro). That doesn't mean it should be ignored. Of course not.

 

However, for being a relatively new supplement, it has already compiled a large volume of research, most of which does not indicate negative side effects. So far, the balance of research would seem to indicate that MitoQ is effective in slowing some aspects of aging. https://www.ncbi.nlm...d/?term="mitoq"   and https://www.mitoq.co...-collaborations

 



#17 BioHacker=Life

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Posted 06 January 2019 - 01:43 AM

Legalization of Hemp extracts and CBD I think would be the biggest next to NAD+. Hemp products are going mainstream within the next 5 years.


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#18 xEva

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Posted 06 January 2019 - 01:47 AM

Anyone know what the human equivalent dose would be? Most studies on animals use an astronomical amount of the compound.

I believe it said the were given 500 nmol/L how would that be converted to mg?

 

 

MitoQ molecular weight is 678.81 g/mol. For 500 nanomol/L The molarity calculator gave me 339.405 micrograms, == 0.3 milligrams per liter -- which is a tiny, almost homeopathic concentration.


Edited by xEva, 06 January 2019 - 01:49 AM.


#19 xEva

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Posted 06 January 2019 - 01:52 AM

The study was in mice and opossum cells (in vitro). That doesn't mean it should be ignored. Of course not.

 

However, for being a relatively new supplement, it has already compiled a large volume of research, most of which does not indicate negative side effects. So far, the balance of research would seem to indicate that MitoQ is effective in slowing some aspects of aging. https://www.ncbi.nlm...d/?term="mitoq"   and https://www.mitoq.co...-collaborations

 

Don't worry be happy? :) Turns out, the major structural molecular backbone of the of MitoQ is the same as DTPP, dodecyl triphenylphosphomium, which consists of TPP (an organophosphorus compound) and the alkyl chain. The toxic effects of MitoQ were recreated by DTPP (50 μmol/L).

 

Maybe you skipped this part? -:

 

We have made the surprising and unexpected finding that MitoQ causes acute mitochondrial swelling and depolarization in PT cells. Since this effect can be recreated by DTPP, which lacks the quinone group of MitoQ, but not by SS‐31, it is highly unlikely to be related to anti‐oxidant activity. Moreover, we did not observe a decrease in OCR, suggesting that OXPHOS function is not inhibited. Acute mitochondrial swelling in pathological states is often attributed to the opening of a large pore in the IMM called the mitochondrial permeability transition pore (mPTP) (Biasutto et al. 2016). However, since we showed that DTPP increased the permeability of liposomes, which lack the components of the mPTP, a direct effect on membrane properties is a more likely explanation for mitochondrial swelling, which is biologically plausible as the alkyl chain is thought to insert into the IMM {==inner mitochondrial membrane].

 

Although some recent reports have raised concerns about adverse effects of MitoQ, to the best of our knowledge our study is the first to directly demonstrate rapid mitochondrial swelling and dissipation of Δψ m in mammalian cells, and to provide a clear mechanistic explanation for this effect. Of note, a previous group reported evidence of mitochondrial swelling induced by DTPP in isolated yeast mitochondria (Trendeleva et al. 2012).

 

Take a look at the MitoQ molecule and its components. They say that DTPP is what messes the membranes:

Attached Files


Edited by xEva, 06 January 2019 - 02:02 AM.

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#20 sthira

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Posted 06 January 2019 - 03:18 AM

Don't worry be happy? :)


From my notes, which are total plagiarism from somewhere I forgot to reference:

"While MitoQ is a synthetic supplement, there is a potent mitochondria-directed antioxidant found in food, especially mushrooms: ergothioneine.

"The exotic mushrooms have even more ergothioneine. The same standard serving size of shiitake, oyster, king oyster or maitake (hen of the woods) can contain up to 13mg in a 3-ounce serving or about 40 times as much as wheat germ.

"Great sources: King Trumpet Mushrooms, King Bolete Mushrooms, Oyster Mushrooms

"Good sources: Portabello Mushrooms, Champignon Mushrooms, White Button, Shiitake Mushrooms ; Black Beans, Kidney Beans, Oat Bran, Garlic..."

Meanwhile: "Mushroom hunting is pretty low tech, but there are a few cool tools you can bring along to make your expedition easier and more efficient..." https://www.thespruc...g-tools-1337947
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#21 baccheion

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Posted 11 January 2019 - 02:26 AM

Iodine (protocol)..
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#22 RichardAlan

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Posted 13 January 2019 - 04:19 AM

Iodine (protocol)..

 

What evidence do you have to back this up?  I have never heard of anyone mention this.



#23 baccheion

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Posted 13 January 2019 - 12:14 PM

What evidence do you have to back this up? I have never heard of anyone mention this.

See Optimox's website for studies..

#24 BioHacker=Life

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Posted 14 January 2019 - 11:28 PM

What evidence do you have to back this up?  I have never heard of anyone mention this.

 

For good reason. They all died.


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#25 Guest

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Posted 16 January 2019 - 03:49 PM

For me there are 2 rising "stars" in the last handful of years. For that I use 2 metrics:

 

 

- how convincing is the emerging scientific evidence in humans? This means especially either a) high quality RCT or b) large scale epidemological studies AND ideally a plausible mechanism of action (as to try to gauge out causality)

 

- how safe is a commonly applied dosage; i.e. are there major side effects that limits its use?

 

 

1. Glycosaminglycan (that is Glucosamine and Chondritine)

 

Back in 2009 preliminary results on the VITAL-study cohort indicated, that those substances don't do much for cartilage. But: they might have a substantial effect on cancer. (Note - Glucosamine is metabolised into N-acetylglucosamine in humans which makes the two polysaccharids identical in function in vivo).  Now there are follow up studies published on that:

 

2013: https://www.ncbi.nlm...pubmed/23529472

again from VITAL: 45% lower risk for colorectoral cancer

 

2016: https://www.ncbi.nlm...pubmed/27357024

the Nurse Health Study: 25% reduction in crc

 

2018: https://www.ncbi.nlm...pubmed/29411204

the cancer prevention study II: 17% reduction in crc

 

2018: https://www.ncbi.nlm...pubmed/29391578

MCC-Spain study: 53% reduction in crc (but due to study design/cohort size not being able to disentagle NSAID use)

 

Note: these studies investigated crc, as it is the most common unisex, non-smoking induced cancer; but similar results where shown for "all cancers" in VITAL and lung cancer in particular (follow up studies on that, too) in the initial VITAL analysis that started the fuss

 

a possible mechanism has been establised:

2017: https://www.ncbi.nlm...pubmed/28713921

in an in-vitro study it prevents down regulation of transcription factors of the most potent tumor supressor genes in humans

 

 

It has been established, that there is a dose-depend effect on its in-vivo action. That might explain the different extend of tumor supression in the different studies.

 

As the side effects are neglible and it's literally dirt cheap, I started taking it last year (2 x 1500 mg daily). For me it's almost (but not quite) in the same department as Vitamin K2 at the moment (just for cancer instead of CVD)

 

 

2. Lithium (somewhat distant second)

 

The situation is a little different. After the initial 2009 study for Lithium water content in japanese provinces - establishing a link between all-cause mortality not linked to it's anti-depressive effects - researches published similar analysis in the high-use-cohorts of Lithium: bi-polar folks.

 

2015: https://www.scienced...165032715002888

Finland: all-cause mortality lowered by 49%; though the study is not that useful as it's a small cohort and not factoring out suicide mortality reduction in the at-risk cohort

 

2016: https://onlinelibrar....1111/bdi.12361

indication of tumor-supressing outcomes in a swedish bi-polar cohort

 

2016: https://www.ncbi.nlm...pubmed/27388574

a dose-dependend reduction in cancer risk: 45% reduction in all cancers (small cohort, but good statistical) analysis

 

2018: https://www.nature.c...cles/npp2017238

a general review of current evidence for various effects of Lithium

 

and potential explanations for the tumor-supressing qualities of Lithium consumption:

2016: https://www.nature.c...icles/srep20739

2018: https://www.ncbi.nlm...pubmed/29708074 (review)

(note: the specific mechanism of action is less clear than for glucosamine)

 

Take home message: Lithium has various benefits, especially for mood disorders. Unlike clinical anti-depressants it does not increase suicide risk (a long standing issue with anti-depressant use in the general population). There is reduction in all-cause mortality beyond that, possibly linked reduction in cancer incidence. Side effects are minimal for the common over-the-counter pills (containing typically 5 mg of elemental Lithium).

 

Caution! The dose-depended risk reduction for cancer was most notable in pharmacological dosage of Lithium of 100 mg - 200 mg of elemental Lithium a day! DO NOT take this doses unless prescribed and monitored by a doctor. Lithium consumption at that level can easily cause (severe) toxcity and has reportedly lead to death by acute and chronic poisoning.

 

If you stick to the otc doses of 5 mg a day you're safe with a favourable risk-reward-ration (and cost-reward-ratio).


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#26 dosquito

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Posted 17 January 2019 - 12:58 AM

What form of glucosamine do you take? and do you notice any effects from lithium?

#27 Guest

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Posted 17 January 2019 - 12:28 PM

glucosamine sulfate (and lithium aspartate if that's the next question)

 

 

By the way, I don't get why Glucosamine/Chondrotine (both are metabolized smiliarly, with the former undertaking an additional conversion cycle) and their effect on cancer and total mortality is not discussed more.

 

 

With the right life style choices and modern medicine you can almost eliminate death directly attributed to cardiovascular disease. But - even if you avoid known carcinogens (smoking, UV-rays, certain chemicals etc. etc.) - there is still a very high risk for developing cancer in a currently typical life span. Also results of medical treatments are by far not up to the level possible for CVD. As for supplements: so far, almost NOTHING works for cancer in HUMANS - judged by good scientifical standards.

 

NSAID - Aspirin etc. - turned out to be useless in recent large scale, high quality studies. Vitamin D doesn't prevent cancer (though influences cancer survival) in recent large scale, high quality studies. Not to speak of a dozend of other supps, for which quality data in HUMANS doesn't even exist.

 

 

The question in the last years was, if the first study that suggested a strong effect of Gluco/Chon on cancer and mortality in a large scale study was a fluke.

 

 

In the last 3 years we got evidence, that this is not the case. More independent studies replicated the same results. Moreover: there are no neutral or negative results. Also as a remark to my previous post: I would'nt discount the spanish study. In one of the papers for the VITAL study the effect of Gluco/Chon increased from 17% lower mortality to 38%-49% reduced mortality upon exclusion of NSAID users. In addition NSAID had no cancer prevention effects in recent quality studies. But: all studies investigating the effect of Gluco/Chon on cancer are affirmative. And we know a plausible mechanism: it inhibits the natural downregulation of tumor supressor genes in humans. If a future RCT or non-VITAL large scale study confirms this trend:

 

 

This is huge!

 

 

 

As I got the impression, that even folks in this forum are not up-to-date about the recent results in Glucosamine studies, I suggest sharing this information or linking to this thread. Or maybe someone opening a dedicated new one - this is miles ahead of the claimed effects of C60, senolytics or resveratrol. In actual magnitude in humans + scientific backing. U wanna do some DIY-experimenting? Get a good cancer model in mice and feed'em glucosamine to figure out the exact dose dependency.


Edited by TFC, 17 January 2019 - 12:47 PM.

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#28 dosquito

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Posted 17 January 2019 - 01:46 PM

I get your experiment. The studies are promising but far from RCT (I glanced at them). I'm surprised if there's nothing else out there that's shown similar correlations in similar types of studies


the results seem too good to be true. basically they found some people who claimed to take glucosamine then followed up years later. what are the odds that those people kept taking glucosamine that whole time? Isn't it likely that they were just more active and it's a spurious correlation? Just thinking out loud - I didn't read in detail

why would tumor suppressor genes be naturally downregulated?

Edited by dosquito, 17 January 2019 - 01:55 PM.

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#29 QuestforLife

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Posted 17 January 2019 - 03:00 PM

glucosamine sulfate (and lithium aspartate if that's the next question)

 

 

By the way, I don't get why Glucosamine/Chondrotine (both are metabolized smiliarly, with the former undertaking an additional conversion cycle) and their effect on cancer and total mortality is not discussed more.

 

 

With the right life style choices and modern medicine you can almost eliminate death directly attributed to cardiovascular disease. But - even if you avoid known carcinogens (smoking, UV-rays, certain chemicals etc. etc.) - there is still a very high risk for developing cancer in a currently typical life span. Also results of medical treatments are by far not up to the level possible for CVD. As for supplements: so far, almost NOTHING works for cancer in HUMANS - judged by good scientifical standards.

 

NSAID - Aspirin etc. - turned out to be useless in recent large scale, high quality studies. Vitamin D doesn't prevent cancer (though influences cancer survival) in recent large scale, high quality studies. Not to speak of a dozend of other supps, for which quality data in HUMANS doesn't even exist.

 

 

The question in the last years was, if the first study that suggested a strong effect of Gluco/Chon on cancer and mortality in a large scale study was a fluke.

 

 

In the last 3 years we got evidence, that this is not the case. More independent studies replicated the same results. Moreover: there are no neutral or negative results. Also as a remark to my previous post: I would'nt discount the spanish study. In one of the papers for the VITAL study the effect of Gluco/Chon increased from 17% lower mortality to 38%-49% reduced mortality upon exclusion of NSAID users. In addition NSAID had no cancer prevention effects in recent quality studies. But: all studies investigating the effect of Gluco/Chon on cancer are affirmative. And we know a plausible mechanism: it inhibits the natural downregulation of tumor supressor genes in humans. If a future RCT or non-VITAL large scale study confirms this trend:

 

 

This is huge!

 

 

 

As I got the impression, that even folks in this forum are not up-to-date about the recent results in Glucosamine studies, I suggest sharing this information or linking to this thread. Or maybe someone opening a dedicated new one - this is miles ahead of the claimed effects of C60, senolytics or resveratrol. In actual magnitude in humans + scientific backing. U wanna do some DIY-experimenting? Get a good cancer model in mice and feed'em glucosamine to figure out the exact dose dependency.

 

Glucosamine - the clue's in the name - almost certainly has benefit through competing with glucose metabolism, and hence burning of more fats. I expect the upregulation of various genes is downstream of that (after all burning fats produces more ROS).

 

It's highly likely a low carb diet would be even more beneficial.



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#30 sthira

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Posted 17 January 2019 - 06:15 PM

Glucosamine -
...

Why does it unfailingly give me hemorrhoids?

Edit: spelling, even spelling the word hemorrhoids is annoying

Edited by sthira, 17 January 2019 - 06:17 PM.

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