62 replies to this topic

[Bateau]

Markups in the retail supplement industry are pretty high. Bulk berberine HCl seems to run $5-20/kg, so its reasonable that Piping Rock can encapsulate $0.25-$1.00 of the powder, randomly check batches for adulterants, and sell for $11 and still make a profit.

 

Even when purchased from laboratory reagent suppliers berberine HCl is only 97-98% pure, with around 20 ppm heavy metals - ie, reasonable for a hot solvent extract from a natural source.

 

I've only bought chemically defined things from Piping-Rock (USP glycine, nicotinic acid, berberine HCl, D3), never enyzmes, probiotics, or ill-defined herbals. Their prices are reasonable given the wholesale costs and the direct-to-consumer model, and their glycine is appropriately sweet, their niacin gives me the proper flush, their berberine has the right colour index. Piping Rock appears to be just a new iteration of a 40 year, three generation family business, so they have strong incentives to maintain quality standards. They're a bit slower in shipping than my other usual supplement sources, Vita-cost and PureBulk, and don't carry some supplements that I prefer, like high-potency K2 M7 and algal-source EPA.

 

Alibaba prices and certified supplier prices are somewhat different. Pretty sure high-potency berberine (98%) is one of the more expensive supplements to get from certified suppliers ATM. Closer to $75-125/kg.

 

Never heard of PureBulk. Ill have to check them out.

 

 

Edited by Bateau, 25 July 2015 - 08:53 PM.

[Darryl]

I'll add, in case Bateau wasn't aware, that Scott Rudolph was formerly Chairman of NTBY, Inc., the supplement manufacturer of Nature's Bounty, Vitamin World, Puritan's Pride, Holland & Barrett, Rexall, Sundown, MET-Rx, Worldwide Sport Nutrition, American Health, GNC (UK), DeTuinen, LeNaturiste, SISU, Solgar, Good 'n' Natural, Home Health, Julian Graves, Ester-C and Natural Wealth brands. They were bought out for $3.8 billion by the Carlyle Group in 2010, so there's no shortage of capital or industry expertise at Piping Rock. It looks like Scott wanted to set up and pass on a growing supplement firm to his son Michael, as his own father did with Nature's Bounty.

[Bateau]

Was totally unaware. Thanks for the info!

[Michael]

Diabetics taking metformin have 15% lower mortality than age matched non-diabetics.

 

The study claiming this has some serious methodological problems; I put no stake in it. And, as a reminder: metformin has been tested now at high and low doses in normal, healthy mice, and also in a somewhat flawed study in rats, and in no case was there an increase in maximum lifespan; there was a very slight (≈5%) increase in average LS in the mouse studies, which might well be due to residual effects of a diet of lab chow and no exercise.

[Kevnzworld]

Diabetics taking metformin have 15% lower mortality than age matched non-diabetics.

The study claiming this has some serious methodological problems; I put no stake in it. And, as a reminder: metformin has been tested now at high and low doses in normal, healthy mice, and also in a somewhat flawed study in rats, and in no case was there an increase in maximum lifespan; there was a very slight (≈5%) increase in average LS in the mouse studies, which might well be due to residual effects of a diet of lab chow and no exercise.

Those that are of the CR religious persuasion find problems in any study that finds any possibility of lifespan extension from any other means than CR....even though CR studies with primates are inconclusive....at best.
There are " problems " with every study I've read if you want to find them, including the ITP studies that showed lifespan extension with green tea extract, curcumin and resveratrol . We take them as they are,..or not

[normalizing]

 

Diabetics taking metformin have 15% lower mortality than age matched non-diabetics.

 

The study claiming this has some serious methodological problems; I put no stake in it. And, as a reminder: metformin has been tested now at high and low doses in normal, healthy mice, and also in a somewhat flawed study in rats, and in no case was there an increase in maximum lifespan; there was a very slight (≈5%) increase in average LS in the mouse studies, which might well be due to residual effects of a diet of lab chow and no exercise.

 

 

but metformin didnt decrease lifespan even if there is nothing seriously noticable in increasing it. so how is it bad to go for it even to be lucky enough to get maybe 5% or so increase?

[nowayout]

 

Diabetics taking metformin have 15% lower mortality than age matched non-diabetics.

 

The study claiming this has some serious methodological problems; I put no stake in it. And, as a reminder: metformin has been tested now at high and low doses in normal, healthy mice, and also in a somewhat flawed study in rats, and in no case was there an increase in maximum lifespan; there was a very slight (≈5%) increase in average LS in the mouse studies, which might well be due to residual effects of a diet of lab chow and no exercise.

 

 

Thank you for the link.  Interesting how something like that 15% claim can become a common wisdom despite being based on some very shaky statistical abracadabra. 
 

[Kevnzworld]

Here is a link to the actual Metformin study
http://onlinelibrary.../dom.12354/full

What is missing from the analysis that is attempting to debunk the study's results is the following:
No one is denying that age matched diabetics on Meformin had better survival numbers than matched non diabetic controls during the length of the study period. Yes there are confounding variables , as one would expect with humans.
Yes the study was limited in length ...and yes, some diabetics needed to be switched to other medications if Metformin didn't control their diabetes and then were eliminated from the study. ( they subsequently then had poorer outcomes ).
But, it is interesting that a fairly large group of relatively unhealthy people on Metformin did have better survival numbers than their healthier counterparts not on Metformin.
This begs the bigger question : how much better survival would healthy adults on a Metformin have versus matched healthy controls not on the drug? Certainly better than diabetics.
If one also factors in the reduced cancer rates for Metformin users that was published in other studies, it makes use of the drug that much more potentially beneficial.

[nowayout]

This begs the bigger question : how much better survival would healthy adults on a Metformin have versus matched healthy controls not on the drug? Certainly better than diabetics.

 

The thing is, that doesn't necessarily follow.  As intuitive as it may seem, it is not actually a logical consequence of the rest of what you write.   The majority of drug trials that intuitively should be successful actually fail, which is why drug development is so expensive in the first place. 
 

[nowayout]

 

This begs the bigger question : how much better survival would healthy adults on a Metformin have versus matched healthy controls not on the drug? Certainly better than diabetics.

 

The thing is, that doesn't necessarily follow.  As intuitive as it may seem, it is not actually a logical consequence of the rest of what you write.   The majority of drug trials that intuitively should be successful actually fail, which is why drug development is so expensive in the first place.

 

Let me expand.

 

The cited study has a built in selection bias.  The only patients who were kept were the ones who had what one could call property X (maybe genetics or environment), which made their diabetes responsive to metformin monotherapy.  Diabetic patients who didn't have property X were dropped ("censored") from the final analysis.

 

Patients with property X had lower mortality than controls, BUT the comparison would only have been valid if controls had ALSO been selected to have property X, which they weren't, since property X is unknown.  Who knows, maybe controls with property X had even lower mortality.
 

[Kevnzworld]

This begs the bigger question : how much better survival would healthy adults on a Metformin have versus matched healthy controls not on the drug? Certainly better than diabetics.

The thing is, that doesn't necessarily follow. As intuitive as it may seem, it is not actually a logical consequence of the rest of what you write. The majority of drug trials that intuitively should be successful actually fail, which is why drug development is so expensive in the first place.

Let me expand.

The cited study has a built in selection bias. The only patients who were kept were the ones who had what one could call property X (maybe genetics or environment), which made their diabetes responsive to metformin monotherapy. Diabetic patients who didn't have property X were dropped ("censored") from the final analysis.

Patients with property X had lower mortality than controls, BUT the comparison would only have been valid if controls had ALSO been selected to have property X, which they weren't, since property X is unknown. Who knows, maybe controls with property X had even lower mortality.

True, but Metformin has been an approved drug for decades, we know it's side effect profile and there've been literally hundreds of studies done with it.
The researchers in this study wanted to isolate it's effects but being a study using humans, not rodents they had to allow unresponsive patients to use other drugs. Confounding variables dictated that they then not be included in the study.
We know that property X is type two diabetic mellitus. A long studied syndrome .
We know that subjects using the other diabetic therapies had worse outcomes than controls.
It's highly unlikely that non diabetics using Metformin would have worse longevity outcomes than diabetics. We know that it activates AMPK and improves insulin sensitivity, both MOA 's would be congruent with better health outcomes and longevity.
I believe I've read that a large scale study is currently being done on non diabetics using Metformin. Unfortunately it will take years, if not a decade to complete. I believe that there is enough published evidence to justify the supervised use of Metformin in non diabetics for health and longevity purposes.

[nowayout]

This begs the bigger question : how much better survival would healthy adults on a Metformin have versus matched healthy controls not on the drug? Certainly better than diabetics.

The thing is, that doesn't necessarily follow. As intuitive as it may seem, it is not actually a logical consequence of the rest of what you write. The majority of drug trials that intuitively should be successful actually fail, which is why drug development is so expensive in the first place.

Let me expand.

The cited study has a built in selection bias. The only patients who were kept were the ones who had what one could call property X (maybe genetics or environment), which made their diabetes responsive to metformin monotherapy. Diabetic patients who didn't have property X were dropped ("censored") from the final analysis.

Patients with property X had lower mortality than controls, BUT the comparison would only have been valid if controls had ALSO been selected to have property X, which they weren't, since property X is unknown. Who knows, maybe controls with property X had even lower mortality.

True, but Metformin has been an approved drug for decades, we know it's side effect profile and there've been literally hundreds of studies done with it.
The researchers in this study wanted to isolate it's effects but being a study using humans, not rodents they had to allow unresponsive patients to use other drugs. Confounding variables dictated that they then not be included in the study.
We know that property X is type two diabetic mellitus. A long studied syndrome .
We know that subjects using the other diabetic therapies had worse outcomes than controls.
It's highly unlikely that non diabetics using Metformin would have worse longevity outcomes than diabetics. We know that it activates AMPK and improves insulin sensitivity, both MOA 's would be congruent with better health outcomes and longevity.
I believe I've read that a large scale study is currently being done on non diabetics using Metformin. Unfortunately it will take years, if not a decade to complete. I believe that there is enough published evidence to justify the supervised use of Metformin in non diabetics for health and longevity purposes.

Property X cannot be type II diabetes, though, since only some of the type II diabetes patients in the trial had property X, i.e., were able to control their diabetes with metformin only.

Maybe they could do this because they benefited from certain genetic or environmental advantages the other patients didn't have, for example, so a comparison of this subpopulation of diabetes patients with the control group cannot be valid.

Edited by nowayout, 28 July 2015 - 03:47 PM.

[Darryl]

The "Property X" may have little to do with therapeutic responsiveness to biguanides (metformin) vs. sulfonylureas vs. thiazolidinediones during the study period, and more to due with medical marketing and changing perceptions of risks, which would randomize the patient population.

 

It should be noted that as metformin has been off patent for decades, the majority of medical marketing during the study period went to newer compounds in the thiazolidinedione (rosiglitazone, pioglitazone), sulfonylurea (glipizide, gliclazide, glibenclamide, etc.) and SGLT-2 inhibitor (canagliflozin, dapagliflozin, empagliflozin) classes.

 

Metformin is now considered the first line treatment for diabetes, however, the metformin & mortality risk study interval begins in 2000, before the landmark studies demonstrating low risk of lactic acidosis with metformin (2003) and elevated cardiovascular risk with rosiglitazone (2007). These markedly change the perception of adverse effects, and initial prescriptions for metformin at diabetes diagnosis went from roughly 23-30% to 53-57% over this interval.

 

As with salicylates and glucosamine, I don't think we're looking at huge effects (~ 5% for each), and it appears that the mild AMPK activation in each case largely inhibits metabolic disease progression, rather than underlying aging. So median lifespans on lab chow and Western diets increase, while maximum lifespan is unchanged.

 

To effect more fundamental effects in retarding aging seems to require going downstream to mTOR inhibition, with CR, intermittent fasting and/or protein/methionine restriction. But given these three compounds are cheap, relatively safe, and may exert synergistic effects on AMPK signalling, I think they're still attractive as add-on supplements to the dietary restriction regimens.

[Kevnzworld]

There isn't any supplement or intervention that been proven to extend lifespan in humans ( Metformin maybe ) because those trials and studies have never been done. Rodents are as close as we can get due to their mammalian short lifespan, and for other ethical reasons.
Creatine, is one supplement that was shown to extend median lifespan ( healthspan ) in wild type mice. This is important because these weren't genetically modified mice. The increase was 9% over control mice.. That's over eight years in human terms, pretty significant.
Quote:
" we investigated the effect of oral creatine supplementation on aging in 162 aged wild-type C57Bl/6J mice. The median healthy life span of creatine-fed mice was 9% higher than in their control littermates, and they performed significantly better in neurobehavioral tests. "

http://link.springer...0726-011-0850-1

Edited by Kevnzworld, 03 August 2015 - 04:03 AM.

[niner]

There isn't any supplement or intervention that been proven to extend lifespan in humans ( Metformin maybe ) because those trials and studies have never been done. Rodents are as close as we can get due to their mammalian short lifespan, and for other ethical reasons.
Creatine, is one supplement that was shown to extend median lifespan ( healthspan ) in wild type mice. This is important because these weren't genetically modified mice. The increase was 9% over control mice.. That's over eight years in human terms, pretty significant.

 

The problem with mice is that it's relatively easy to make them live longer.  The lifespan increases won't translate directly to humans-- it's likely to be much smaller.  There are other options besides rodents-- primates, for example, are much closer to humans, but have some of the same problems as human experimental animals; they're expensive and their lifespan is too long.  Other mammals of intermediate lifespan, like dogs, cats, or various farm animals are another possibility.  When an intervention shows a beneficial lifespan effect in multiple species, that's a better indication that it will be useful and non-toxic in humans.

 

Another way to evaluate a substance in humans is to look at biomarkers.  This is of course a weaker form of evidence, but is quick, usually cheap, and can give useful information.

[Darryl]

Lithium is another promising anti-aging compound in humans, with a plausible mechanism:

 

Zarse K et al. 2011. Low-dose lithium uptake promotes longevity in humans and metazoans. European journal of nutrition, 50(5), 387-389.

 

In humans, we find here an inverse correlation between drinking water lithium concentrations and all cause mortality in 18 neighboring Japanese municipalities with a total of 1,206,174 individuals

 

Sarkar S et al. 2005. Lithium induces autophagy by inhibiting inositol monophosphatase. The Journal of cell biology, 170(7), 1101-1111.

 

Here we describe a novel mTOR-independent pathway that regulates autophagy. We show that lithium induces autophagy, and thereby, enhances the clearance of autophagy substrates, like mutant huntingtin and α-synucleins. This effect is not mediated by glycogen synthase kinase 3β inhibition. The autophagy-enhancing properties of lithium were mediated by inhibition of inositol monophosphatase and led to free inositol depletion. This, in turn, decreased myo-inositol-1,4,5-triphosphate (IP3) levels. Our data suggest that the autophagy effect is mediated at the level of (or downstream of) lowered IP3, because it was abrogated by pharmacologic treatments that increased IP3. This novel pharmacologic strategy for autophagy induction is independent of mTOR, and may help treatment of neurodegenerative diseases, like Huntington's disease, where the toxic protein is an autophagy substrate.

 

That study, incidentally, has been cited by numerous studies identifying non-psychiatric benefits for lithium, mostly in neurodegenerative diseases. Some highlights:

 

Neurodegeneration:

Fornai F et al. 2008. Lithium delays progression of amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences, 105(6), 2052-2057.

Camins A et al. 2009. Potential mechanisms involved in the prevention of neurodegenerative diseases by lithium. CNS neuroscience & therapeutics, 15(4), 333-344.

Heiseke A et al. 2009. Lithium induces clearance of protease resistant prion protein in prion‐infected cells by induction of autophagy. Journal of neurochemistry, 109(1), 25-34.

Caldero J et al. 2010. Lithium prevents excitotoxic cell death of motoneurons in organotypic slice cultures of spinal cord. Neuroscience, 165(4), 1353-1369.

Leroy K et al. 2010. Lithium treatment arrests the development of neurofibrillary tangles in mutant tau transgenic mice with advanced neurofibrillary pathology. Journal of Alzheimer's disease, 19(2), 705.

Zhang X et al. 2010. Long-term treatment with lithium alleviates memory deficits and reduces amyloid-β production in an aged Alzheimer's disease transgenic mouse model. Journal of Alzheimer's disease: JAD, 24(4), 739-749.

Chang JW et al. 2011. Lithium rescues the impaired autophagy process in CbCln3Δex7/8/Δex7/8 cerebellar cells and reduces neuronal vulnerability to cell death via IMPase inhibition. Journal of neurochemistry, 116(4), 659-668.

Kim YH et al. 2011. Lithium protects against oxidative stress‐mediated cell death in α‐synuclein‐overexpressing in vitro and in vivo models of Parkinson's disease. Journal of neuroscience research, 89(10), 1666-1675.

Forlenza OV et al. 2012. Does lithium prevent Alzheimer’s disease?. Drugs & aging, 29(5), 335-342.

Shimada K et al. 2012. Long-term oral lithium treatment attenuates motor disturbance in tauopathy model mice: implications of autophagy promotion.Neurobiology of disease, 46(1), 101-108.

Trujillo-Estrada L et al. 2013. In vivo modification of Abeta plaque toxicity as a novel neuroprotective lithium-mediated therapy for Alzheimer’s disease pathology. Acta neuropathologica communications, 1(1), 73.

Wu S et al. 2013. Lithium down-regulates histone deacetylase 1 (HDAC1) and induces degradation of mutant huntingtin. Journal of Biological Chemistry,288(49), 35500-35510.

Sofola-Adesakin O et al. 2014. Lithium suppresses Aβ pathology by inhibiting translation in an adult Drosophila model of Alzheimer's disease.Frontiers in aging neuroscience, 6.

Forlenza OV et al. 2014. Neuroprotective effects of lithium: implications for the treatment of Alzheimer’s disease and related neurodegenerative disorders. ACS chemical neuroscience,5(6), 443-450.

Mauer S et al. 2014. Standard and trace-dose lithium; A systematic review of dementia prevention and other behavioral benefits. Australian and New Zealand Journal of Psychiatry, 48(9), 809-818.

 

CVD:

Struewing IT et al. 2007. Lithium increases PGC‐1α expression and mitochondrial biogenesis in primary bovine aortic endothelial cells. FEBS Journal, 274(11), 2749-2765.

De Meyer I et al. 2011. Inhibition of inositol monophosphatase by lithium chloride induces selective macrophage apoptosis in atherosclerotic plaques. British journal of pharmacology, 162(6), 1410-1423.

Liu A. et al. 2013. Chronic lithium treatment protects against liver ischemia/reperfusion injury in rats. Liver Transplantation,19(7), 762-772.

 

Cancer:

Neel BD et al. 2009. Lithium suppresses motility and invasivity of v-src-transformed cells by glutathione-dependent activation of phosphotyrosine phosphatases. Oncogene, 28(36), 3246-3260.

Ronchi A et al. 2010. Lithium induces mortality in medulloblastoma cell lines. International journal of oncology, 37(3), 745-752.

 

Other:

Kim EC et al. 2013. Lithium treatment increases endothelial cell survival and autophagy in a mouse model of Fuchs endothelial corneal dystrophy. British Journal of Ophthalmology, bjophthalmol-2012.

Martinsson L et al. 2013. Long-term lithium treatment in bipolar disorder is associated with longer leukocyte telomeres. Translational psychiatry, 3(5), e261.

 

A quote from the last study

Lithium-treated bipolar disorder patients overall, as well as those on lithium monotherapy, had 35% longer telomeres compared with controls (P<0.0005, partial η2=0.13). TL correlated positively with lithium treatment duration of >30 months (P=0.031, R2=0.13) and was negatively associated with increasing number of depressive episodes (P<0.007). Bipolar disorder patients responding well to lithium treatment had longer telomeres than those not responding well.

 

 

 

[nowayout]

 

Lithium is another promising anti-aging compound in humans, with a plausible mechanism:

 

Except that it tends to cause kindney failure in the long term, so that one may have to wait until they can grow artificial kidney replacements before taking this seriously. 

 

Oh, and also its mood-blunting side effect, which is a necessary evil in bipolar patients but may not be so welcome in neurotypicals. 
 

Edited by nowayout, 04 August 2015 - 10:20 AM.

[Darryl]

Except that it tends to cause kindney failure in the long term

 

Thanks for the pointer.

 

It seems the rate of kidney failure after long term use is around 0.5%. I'll look into whether microdose lithium as found in some municipal water has any effects on the IP3 signalling/autophagy, and organ toxicity.

 

McKnight RF et al. 2012. Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817), 721-728.

 

There are other IMPase inhibitors that induce autophagy by reducing IP₃ levels (carbemazepine, sodium valproate), alas they have more severe adverse effects than lithium.

 

Most other autophagy inducers lack chronic use studies from which we might infer an off-target mortality effect, with the exception of caffeine.

 

autophagy

Saiki S et al. 2011. Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. Autophagy, 7(2), 176-187.

Sinha RA et al. 2014. Caffeine stimulates hepatic lipid metabolism by the autophagy‐lysosomal pathway in mice. Hepatology, 59(4), 1366-1380.

Mathew TS et al. 2014. Caffeine promotes autophagy in skeletal muscle cells by increasing the calcium-dependent activation of AMP-activated protein kinase. Biochemical and biophysical research communications, 453(3), 411-418.

Moon JH et al. 2014. Caffeine prevents human prion protein-mediated neurotoxicity through the induction of autophagy. International journal of molecular medicine, 34(2), 553-558.

 

eukaryotic lifespan/aging

Wanke V et al. 2008. Caffeine extends yeast lifespan by targeting TORC1.Molecular microbiology, 69(1), 277-285.

Winter G et al. 2008. Caffeine induces macroautophagy and confers a cytocidal effect on food spoilage yeast in combination with benzoic acid. Autophagy, 4(1), 28-36.

Lublin A. 2011. FDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on cbp and protect against proteotoxicity. PLoS One, 6(11), e27762-e27762.

Sutphin GL et al. 2012. Caffeine extends life span, improves healthspan, and delays age-associated pathology in Caenorhabditis elegans. Longevity & healthspan, 1(9).

Rallis, C et al. 2013. TORC1 signaling inhibition by rapamycin and caffeine affect lifespan, global gene expression, and cell proliferation of fission yeast. Aging Cell, 12(4), 563-573.

Strachecka A et al. 2014. Unexpectedly strong effect of caffeine on the vitality of western honeybees (Apis mellifera). Biochemistry (Moscow), 79(11), 1192-1201.

Ullah F et al. 2015. Caffeine prevents D-galactose-induced cognitive deficits, oxidative stress, neuroinflammation and neurodegeneration in the adult rat brain. Neurochemistry international.

 

human mortality

Paganini-Hill A et al. 2007. Non-alcoholic beverage and caffeine consumption and mortality: the Leisure World Cohort Study. Preventive medicine, 44(4), 305-310.

Je Y & Giovannucci E. 2014. Coffee consumption and total mortality: a meta-analysis of twenty prospective cohort studies. British Journal of Nutrition,111(07), 1162-1173.

 

Alas, while caffeine, coffee and tea are associated with benefits in neurodegenerative diseases, the mortality epidemiology is seriously confounded by other constituents of caffeinated beverages. Coffee melanoidins, for example, are important Nrf2 inducers.

[niner]

 

Lithium is another promising anti-aging compound in humans, with a plausible mechanism:

 

Except that it tends to cause kindney failure in the long term, so that one may have to wait until they can grow artificial kidney replacements before taking this seriously. 

 

Oh, and also its mood-blunting side effect, which is a necessary evil in bipolar patients but may not be so welcome in neurotypicals.

 

I wouldn't expect either of these effects at the microdoses (e.g. 5mg/d) used by people around here.  Maybe at therapeutic doses for bipolar disease, but that dosing is orders of magnitude higher.  Microdoses are aimed at recapitulating the positive effects observed in areas where the drinking water has increased Li.  Is there any evidence of a problem at low dose?

[normalizing]

5mg is a microdose? i thought in general lithium is prescribed to about 10mg for bipolar, so how is 5mg microdose? also different types of lithium out there, i believe the water lithium is carbonate which is with low absorption and toxicity hence you can drink a lot of the water containing it versus some of the more potent pharm grade lithium for bipolar people and/or the supplemental lithium sold without prescription.

[cuprous]

5mg is a microdose? i thought in general lithium is prescribed to about 10mg for bipolar, so how is 5mg microdose? also different types of lithium out there, i believe the water lithium is carbonate which is with low absorption and toxicity hence you can drink a lot of the water containing it versus some of the more potent pharm grade lithium for bipolar people and/or the supplemental lithium sold without prescription.

 

Second link on google for "lithium bipolar dosage"  http://www.drugs.com...ge/lithium.html

It's 1,800mg/day.

 

I'm not losing any sleep over 5mg every few days.

[nowayout]

 

5mg is a microdose? i thought in general lithium is prescribed to about 10mg for bipolar, so how is 5mg microdose? also different types of lithium out there, i believe the water lithium is carbonate which is with low absorption and toxicity hence you can drink a lot of the water containing it versus some of the more potent pharm grade lithium for bipolar people and/or the supplemental lithium sold without prescription.

 

Second link on google for "lithium bipolar dosage"  http://www.drugs.com...ge/lithium.html

It's 1,800mg/day.

 

I'm not losing any sleep over 5mg every few days.

 

But what can you expect from 5 mg, given that the (beneficial?) effects on telomeres mentioned above were observed in bipolar patients on high doses?
 

[nowayout]

 

 

 

A quote from the last study

Lithium-treated bipolar disorder patients overall, as well as those on lithium monotherapy, had 35% longer telomeres compared with controls (P<0.0005, partial η2=0.13). TL correlated positively with lithium treatment duration of >30 months (P=0.031, R2=0.13) and was negatively associated with increasing number of depressive episodes (P<0.007). Bipolar disorder patients responding well to lithium treatment had longer telomeres than those not responding well.

 

Problem with this result:

 

Maybe it is the bipolar that shortens telomeres in this model, so neurotypical people may derive no benefit. 

 

Similar objections apply to all the other studies referring to specific disease models.

Edited by nowayout, 05 August 2015 - 07:41 PM.

[niner]

 

A quote from the last study

Lithium-treated bipolar disorder patients overall, as well as those on lithium monotherapy, had 35% longer telomeres compared with controls (P<0.0005, partial η2=0.13). TL correlated positively with lithium treatment duration of >30 months (P=0.031, R2=0.13) and was negatively associated with increasing number of depressive episodes (P<0.007). Bipolar disorder patients responding well to lithium treatment had longer telomeres than those not responding well.

 

Problem with this result:

 

Maybe it is the bipolar that shortens telomeres in this model, so neurotypical people may derive no benefit. 

 

From the paper:

 

 

Participants were outpatients diagnosed with BD type 1 or 2 (n=256) and healthy controls (n=139).

 

This sounds like the people with Bipolar Disorder (BD) had longer telomeres than healthy people.  Maybe instead of messing around with expensive telomerase activators of questionable merit, people should just take lithium, assuming they can get the effect with a safe dose.  The therapeutic index of lithium isn't very good.

[normalizing]

 

5mg is a microdose? i thought in general lithium is prescribed to about 10mg for bipolar, so how is 5mg microdose? also different types of lithium out there, i believe the water lithium is carbonate which is with low absorption and toxicity hence you can drink a lot of the water containing it versus some of the more potent pharm grade lithium for bipolar people and/or the supplemental lithium sold without prescription.

 

Second link on google for "lithium bipolar dosage"  http://www.drugs.com...ge/lithium.html

It's 1,800mg/day.

 

I'm not losing any sleep over 5mg every few days.

 

 

at 1,800 lithium carbonate found in water is quite safe. im not sure which type of pharmo manufactured lithium they give to bipolar people, but i assume its stronger and wont need such high doses anyway.

[nowayout]

 

 

A quote from the last study

Lithium-treated bipolar disorder patients overall, as well as those on lithium monotherapy, had 35% longer telomeres compared with controls (P<0.0005, partial η2=0.13). TL correlated positively with lithium treatment duration of >30 months (P=0.031, R2=0.13) and was negatively associated with increasing number of depressive episodes (P<0.007). Bipolar disorder patients responding well to lithium treatment had longer telomeres than those not responding well.

 

Problem with this result:

 

Maybe it is the bipolar that shortens telomeres in this model, so neurotypical people may derive no benefit. 

 

From the paper:

 

 

Participants were outpatients diagnosed with BD type 1 or 2 (n=256) and healthy controls (n=139).

 

This sounds like the people with Bipolar Disorder (BD) had longer telomeres than healthy people.  Maybe instead of messing around with expensive telomerase activators of questionable merit, people should just take lithium, assuming they can get the effect with a safe dose.  The therapeutic index of lithium isn't very good.

 

Interesting.

 

However, coming from a Physics background, I have to chuckle at how they draw these inferences from scatter plots like this one.  It seems like a reach.  A very imaginative application of statistics is obviously required:

 

 

[Blankspace]

Maybe instead of messing around with expensive telomerase activators of questionable merit, people should just take lithium, assuming they can get the effect with a safe dose.  The therapeutic index of lithium isn't very good.

 

 

Regarding the low therapeutic index of traditional lithium, what do you think of Li3PQQ? The results of this Alzheimer's disease mouse study show that it has a higher potency.

At just 12mg/kg they got similar results on disease marker reduction to that of 100mg/kg of LiCl, without any of the high blood level accumulation that's associated with toxicity.

http://www.ncbi.nlm....pubmed/25018109

[LOOKINGFORTIME]

 oxaloacetic acid 

 

I see that International Anti Aging systems has this in stock. I Wonder if it is worth the price?

 

http://www.antiaging-systems.com/

 

Oxalo-Pro (oxaloacetate) 

30 x 100mg capsules 
59.99

[normalizing]

anti-aging systems are notorious for bumping the price quite high for less the mg and amount per supplement. you can always try searching alternative places for what they have and you will see the difference.

[NeuroGeneration]

Back to the topic of Berberine for a moment, does anyone have any insight into, 1- the potential for genotoxicity, and 2- if it fulfills the purported life-extension properties of metformin (i.e., the same mechanisms). 

 

Regarding 1, here are studies that I came across from someone's Reddit post:

 

Mechanism study of goldenseal-associated DNA damage http://www.ncbi.nlm....pubmed/23747414[1]

"As measured by the Comet assay and the expression of γ-H2A.X, berberine, followed by palmatine, appeared to be the most potent DNA damage inducer in human hepatoma HepG2 cells."

Berberine induces double-strand DNA breaks in Rev3 deficient cellshttp://www.ncbi.nlm....pubmed/24584584[2]

"Following berberine treatment, cell cycle analysis identified that G2/M arrest was increased in Rev3-/- cells. Furthermore, compared with wild-type cells (WT), berberine also induced a significant increase in double-strand breaks (DSBs) in Rev3-/- cells, as revealed by chromosomal aberration (CA) analysis."

Genotoxicity of the isoquinoline alkaloid berberine in prokaryotic and eukaryotic organismshttp://www.ncbi.nlm..../pubmed/7681536[3]

"Among the different repair-deficient mutants examined, a mutant blocked in the DNA strand-break repair pathway (rad52-1) was found to be the most sensitive to the cytotoxic effect of berberine."

Berberine induces apoptosis and DNA damage in MG‑63 human osteosarcoma cellshttp://www.ncbi.nlm....pubmed/25050485[4]

"Furthermore, berberine induced significant concentration- and time-dependent increases in DNA damage compared with that in the negative control [in the MG-63 cells]"

*Toxicology and carcinogenesis studies of goldenseal root powder (Hydrastis Canadensis) in F344/N rats and B6C3F1 mice (feed studies). * http://www.ncbi.nlm....pubmed/21372858[5]

 

Regarding 2, this article ( http://www.inquisitr...n-to-120-years/) mentions that "Researchers believe that metformin works by boosting availability of oxygen to body cells. This boosts the vigor of cells and prolongs their lifespan." Does Berberine do the same? Or is Metformin actually much better for life extension than Berberine?