81 replies to this topic

[david ellis]

 

To expand on my above statement - I was thinking longvida would reduce brain inflammation (since curcumin can cross the blood brain barrier) while bcm-95 would reduce body inflammation (since the metabolites cannot cross the blood brain barrier). I had read a while back that many scientists think the metabolites might actually work better on inflammation...they just won't help with brain inflammation. An alternative would be stacking longvida and boswellia to work more through 5-lox.

 

Active metabolites are not super-common.  I'm not saying that this couldn't be the case with curcumin, but do you have any references that point to activity from curcumin metabolites? (particularly the glucuronide)

 

 

 

You are right about glucuronide, in the You Tube Video - 

 

Curcumin Advancements -The Aging Brain with Longvida® Curcumin.           

 

Dr Gregory Cole, Director of Research, UCLA is quoted "There is not a shred of evidence that curcumin glucuronide gets into the brain."  (found at 18:00 minutes in)    The video considered glucuronide an obstacle to success because the conversion of curcumin to glucuronide reduced the amount of effective curcumin.

Edited by david ellis, 10 March 2015 - 09:20 PM.

[cylon]

So what's the consensus, ditch your longvida and stick with turmeric? Any other studies worth reading?

[stan08]

 

To expand on my above statement - I was thinking longvida would reduce brain inflammation (since curcumin can cross the blood brain barrier) while bcm-95 would reduce body inflammation (since the metabolites cannot cross the blood brain barrier). I had read a while back that many scientists think the metabolites might actually work better on inflammation...they just won't help with brain inflammation. An alternative would be stacking longvida and boswellia to work more through 5-lox.

 

Active metabolites are not super-common.  I'm not saying that this couldn't be the case with curcumin, but do you have any references that point to activity from curcumin metabolites? (particularly the glucuronide)

 

 

I apologize, you're correct.  I reread the study I was basing my comment on and I somehow totally misunderstood it.  I appreciate you asking the question because if you hadn't, I would have gone on thinking (and mentioning to others) something that was incorrect.  

[stan08]

So what's the consensus, ditch your longvida and stick with turmeric? Any other studies worth reading?

 

I would think it might be more the opposite...keep longvida since it's the only one that's been shown to make it into the brain. I just wish it didn't have SSRI-like side effects (at least, for me).  However, even with that it's still the best supplement I've taken.

[Thell]

 

So what's the consensus, ditch your longvida and stick with turmeric? Any other studies worth reading?

 

I would think it might be more the opposite...keep longvida since it's the only one that's been shown to make it into the brain. I just wish it didn't have SSRI-like side effects (at least, for me).  However, even with that it's still the best supplement I've taken.

 

 

For what it is worth, LongVida(SLCP) curcumin is not the only one shown to increase levels in the brain.

 

The most cited article I've seen regarding LongVida's improved brain levels is Frautschy, SA “Improving bioavailability of curcumin by solid lipid particle for treatment of Alzheimer's (AD)” at the 38th Annual Meeting of the Society of Neuroscience , Washington DC, November 15, 2008 which, as far as I can find, was never published. The abstract for the presentation states

 

... After ingestion of 4-10 gms of Curc, plasma levels in humans are < 25 nM, seemingly too low for efficacy in trials for neurological diseases, including AD. Therefore, we investigated stability, blood levels and brain delivery of a new formulation of solid lipidated curcumin particles (SLCP) designed to stabilize the drug and improve bioavailability in neuroinflammation and Alzheimer's (AD) models. ...

Gavage of 5 mg of SLCP formulation A1 into rats, produced 0.635 μM plasma and 2.149 μM brain curc. Without formulation, gavage of plain Curc powder resulted in negligible plasma an brain levels. We established EC50’s (1-2 μM) for inhibition of LPS-induced iNOS, carbonyls and IL-1β. 2 week feeding of SLCP formulations at 500 ppm to mice resulted in brain levels well in excess of these EC50s 9 hours after drug withdrawal. Higher dosing in chow with the highest potency formulation SLCP-176 produced sustained cancer chemotherapeutic brain levels (>20 μM). Gavage of the same SLCP A1 formulation to old, amyloid-laden, but not young APP transgenic animals for as little as 4 days significantly increased levels of Aβ 40 and 42 in plasma and CSF which was interpreted as amyloid clearance from brain. Chronic Curc feeding to triple TG mice suppressed behavior deficits. Therefore, our SLCP formulations are sufficient to improve brain delivery of oral curcumin and suppress inflammation, oxidative damage and amyloid and should be considered for future clinical trials for AD and possibly other CNS conditions with chronic neuroinflammation or amyloid. Higher potency SCLP-176 can be used at low mg doses as opposed to current multiple gram capsules. ...

 

 

 

Looking at studies for other formulations one can find things like this detailed CurQFen study

 

The delivery of significant concentrations of biologically active free curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) at the target tissues has always been regarded as a major limitation for the efficacy of curcumin. Herein we report the blood–brain-barrier permeability, tissue distribution and enhanced bioavailability of free curcuminoids following the oral administration of a food grade curcumin formulation in comparison with the standardized native curcumin, for the first time. UPLC-ESI-MS/MS analyses of post-administration tissue samples of Wistar rats (200 mg/kg body weight) demonstrated significant (p < 0.001) enhancement in plasma bioavailability (25-fold), in vivo stability and blood–brain-barrier permeability as evidenced from the tissue distribution of free curcuminoids at, (ng/g), brain (343 ± 64.7), heart (391.7 ± 102.5), liver (445.52 ± 83), kidney (240.1 ± 47.2), and spleen (229.72 ± 42.2), with extended elimination half-life of 3 to 4 h. Standard curcumin, on the other hand, detected only 1.4 ± 0.8 ng/g of curcumin in the brain tissues.

→ source (external link)

 

I wish there was more actual information regarding the SLCP presentation!

 

5mg seems like a real low dose considering that the SLCP formulation is 80mg curcumin (400mg LongVida). Assuming the A1 formulation matches up with the researched and patented formulation then 5mg would be 1mg curcumin. Most studies I've found use much higher dosages of curcumin than that! For instance, the CurQFen study was 40mg curcumin (100mg CurQFen) with the remainder being fenugreek and the rats in the study are ~210g giving ~16.8mg curcumin.

 

Interestingly it looks like curcumin formulations (cur-PLGA-NP, 'clicked'-sugar curcumin, curr-PLGA-PEG, etc...) that take advantage of BBB glucose transport may yield higher levels with even lower doses. I'd love to be able to take a low dose of something like MetaCurcumin for general availability and another low dose of a PLGA formulation particularly for the brain...

[cylon]

 

So what's the consensus, ditch your longvida and stick with turmeric? Any other studies worth reading?

 

I would think it might be more the opposite...keep longvida since it's the only one that's been shown to make it into the brain. I just wish it didn't have SSRI-like side effects (at least, for me).  However, even with that it's still the best supplement I've taken.

 

Which SSRI specific side effects do you experience?

[stan08]

So what's the consensus, ditch your longvida and stick with turmeric? Any other studies worth reading?

I would think it might be more the opposite...keep longvida since it's the only one that's been shown to make it into the brain. I just wish it didn't have SSRI-like side effects (at least, for me). However, even with that it's still the best supplement I've taken.

Which SSRI specific side effects do you experience?

The main one is extremely reduced libido.

[Arisia]

So what does everyone think of the implications of the following study?

 

http://www.ncbi.nlm....pubmed/25649709

 

 

...We have found that human vascular smooth muscle and endothelial cells derived from aorta are very sensitive to curcumin treatment and can senesce upon treatment with cytostatic doses. We observed characteristic senescence markers but the number of DNA damage foci decreased. Surprisingly, in vascular smooth muscle cell (VSMC) activation of DNA damage response pathway downstream of ataxia-telangiectasia mutated (ATM) was observed. ATM silencing and the supplementation of antioxidants, N-acetyl-L-cysteine (NAC) or trolox, did not reduce the number of senescent cells. Thus, we have shown that curcumin can induce senescence of cells building the vasculature, which is DNA damage and ATM independent and is not induced by increased reactive oxygen species (ROS) level. We postulate that an increase in the bioavailability of curcumin should be introduced very carefully considering senescence induction as a side effect.

 

 

[cylon]

I'd also like to know what the implications are, but more specifically what is meant by 'cytostatic doses' in this case? Many beneficial herbs and supplements can be toxic in extremely high doses, no?

 

As mentioned in this thread

http://www.longecity...damage-and-atm/

 

'it is an in vitro study, which are not all that valuable for guidance on human nutrition. Future in vivo studies will tell a truer tale'

 

 

At the least I guess caution is warranted. But does this mean stay away from any bioavaliable form of c. or to simply use less often? 

Edited by cylon, 13 March 2015 - 01:18 AM.

[DeadMeat]

I assume at least normal dosages should still be safe. Cytostatic effects and increased accumulation of senescent cells is probably hard to detect in a toxicity study. But those in vitro effects were dose dependent. From curcumin not doing much at 1 microM to even starting to kill those normal cells at 10 microM. So if there was an in vivo effect at normal dosages of Longvida curcumin, I assume this would have been noticeable at the very high dosages.

 

http://www.ncbi.nlm....pubmed/21571027

Safety assessment of a solid lipid curcumin particle preparation: acute and subchronic toxicity studies.
Dadhaniya P, Patel C, Muchhara J, Bhadja N, Mathuria N, Vachhani K, Soni MG.

Curcumin, a polyphenol, is obtained from turmeric, the ground rhizomes of Curcuma longa L. Extensive research over the past half century has revealed several health benefits of curcumin. The objective of the present study was to investigate potential adverse effects, if any, of a novel solid lipid curcumin particle (SLCP) preparation in rats following acute and subchronic administration. The oral LD₅₀ of the preparation in rats as well as in mice was found to be greater than 2000 mg/kg body weight (bw). In the subchronic toxicity study, Wistar rats (10/sex/group) were administered via oral gavage 0 (control), 180, 360, and 720 mg/kg bw/day of SLCP preparation for 90 days. Administration of the curcumin preparation did not result in any toxicologically significant treatment-related changes in clinical (including behavioral) observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. No adverse effects of the curcumin preparation were noted on the hematology, serum chemistry parameters, and urinalysis. Terminal necropsy did not reveal any treatment-related gross or histopathology findings. Based on the results of this study, the No Observed-Adverse-Effect Level (NOAEL) for this standardized novel curcumin preparation was determined as 720 mg/kg bw/day, the highest dose tested.

 

 

[stan08]

Well, I stopped the Longvida extract a couple weeks ago and started trying the BCM-95 extract and have to say there's definitely a difference between the two.  Longvida is very similar to my trials with SSRIs in that it's very calming and destroys my libido.  BCM-95 on the other hand is more energizing, better at decreasing lower back pain and seems to increase my libido (almost a little too much).  I'm assuming the difference is due to Longvida actually crossing the blood brain barrier (maybe significantly increasing serotonin levels...hence the similarity to SSRI's?) and BCM-95 is maybe better at increasing circulation and anti-inflammatory effects (maybe due to the other curcuminoids being more effects at reducing inflammation in the body?).  

 

One other negative I don't think I mentioned about Longvida is that it seems to cause some brain fog.  I initially thought it helped with that but I was taking bacopa at the same time.  When I stopped bacopa, I noticed the brain fog came back.  Does anyone know how Longvida could possibly contribute to brain fog?  The only explanation I have is that it's increasing serotonin levels which is a vasoconstrictor.  This action was negated when I took the bacopa because it increased cerebral blood flow (vasodilator).

[DeadMeat]

One other negative I don't think I mentioned about Longvida is that it seems to cause some brain fog.  I initially thought it helped with that but I was taking bacopa at the same time.  When I stopped bacopa, I noticed the brain fog came back.  Does anyone know how Longvida could possibly contribute to brain fog?  The only explanation I have is that it's increasing serotonin levels which is a vasoconstrictor.  This action was negated when I took the bacopa because it increased cerebral blood flow (vasodilator).

 

Am i misreading this or did you have brain fog before starting Longvida curcumin? Although curcumin should be ashamed of itself for not working for something, you can't really blame it for not being bacopa. :p

[stan08]

One other negative I don't think I mentioned about Longvida is that it seems to cause some brain fog. I initially thought it helped with that but I was taking bacopa at the same time. When I stopped bacopa, I noticed the brain fog came back. Does anyone know how Longvida could possibly contribute to brain fog? The only explanation I have is that it's increasing serotonin levels which is a vasoconstrictor. This action was negated when I took the bacopa because it increased cerebral blood flow (vasodilator).

Am i misreading this or did you have brain fog before starting Longvida curcumin? Although curcumin should be ashamed of itself for not working for something, you can't really blame it for not being bacopa. :p

Some brain fog before longvida but worse after longvida. Yeah, there's really nothing like bacopa. I just wish it didn't put me in such a bad mood after more than a week of use. Even longvida wasn't strong enough to counter that. It just seemed like the two would make a perfect stack. Prohealth even makes a capsule which combines the longvida and bacognize extracts.

[DeadMeat]

Some brain fog before longvida but worse after longvida. Yeah, there's really nothing like bacopa. I just wish it didn't put me in such a bad mood after more than a week of use. Even longvida wasn't strong enough to counter that. It just seemed like the two would make a perfect stack. Prohealth even makes a capsule which combines the longvida and bacognize extracts.

 

 

Ah ok. Curcumin does seem to have some possible direct effects on dilation/constriction. Maybe the relatively high blood concentration of curcumin could be causing extra trouble for you. Although from the introduction of that study, curcumins effect on different types of blood vessels, animal and tissue models is a bit confusing and conflicting.

http://www.ncbi.nlm....les/PMC3136562/

Curcumin mediates both dilation and constriction of peripheral arterioles via adrenergic receptors.
Dewar AM1, Clark RA, Singer AJ, Frame MD.

Curcumin has wound healing attributes mediated through a plethora of biological activities that in general are not ascribed to specific receptors. Recently, we have demonstrated that intravenous administration of curcumin limits burn injury progression in a rat model. As decreased microvascular perfusion is a central element of burn injury progression, we hypothesized that curcumin may induce vasodilation in peripheral arterioles, to improve perfusion. Using mucosal microcirculation as an in situ assay, cheek pouch tissue was exteriorized in anesthetized (phentobarbital 70 mg kg(-1) intraperitoneal) male hamsters (N=60) to observe the terminal feed arterioles (∼8 μm diameter) and the immediately upstream arcade arterioles (∼20 μm). Curcumin (10(-12)-10(-4) mol l(-1)) was applied dose-wise (micropipette, 60 seconds). Subnanomolar curcumin dilated, whereas micromolar doses constricted, the arterioles. For the terminal arteriole: vasodilation logEC(50) -10.3±0.2, peak dilation +39±1%; vasconstriction logEC(50) -8.0±0.4, peak constriction -14±2%. Simultaneous atropine (muscarinic antagonist) or PD142893 (endothelin antagonist) had no effect. Propranolol (β-adrenergic receptor (β-Ad) antagonist) enhanced constriction by removing the vasodilation response to curcumin. Phentolamine (α-adrenergic receptor (α-Ad) antagonist) enhanced dilation to curcumin by removing the vasoconstriction response. Thus, the curcumin vasomotor activity on microcirculation was α-Ad and β-Ad receptor-dependent and its net vasoactive effect was concentration- and time-dependent.

 

[stan08]

 

Some brain fog before longvida but worse after longvida. Yeah, there's really nothing like bacopa. I just wish it didn't put me in such a bad mood after more than a week of use. Even longvida wasn't strong enough to counter that. It just seemed like the two would make a perfect stack. Prohealth even makes a capsule which combines the longvida and bacognize extracts.

 

 

Ah ok. Curcumin does seem to have some possible direct effects on dilation/constriction. Maybe the relatively high blood concentration of curcumin could be causing extra trouble for you. Although from the introduction of that study, curcumins effect on different types of blood vessels, animal and tissue models is a bit confusing and conflicting.

http://www.ncbi.nlm....les/PMC3136562/

Curcumin mediates both dilation and constriction of peripheral arterioles via adrenergic receptors.
Dewar AM1, Clark RA, Singer AJ, Frame MD.

Curcumin has wound healing attributes mediated through a plethora of biological activities that in general are not ascribed to specific receptors. Recently, we have demonstrated that intravenous administration of curcumin limits burn injury progression in a rat model. As decreased microvascular perfusion is a central element of burn injury progression, we hypothesized that curcumin may induce vasodilation in peripheral arterioles, to improve perfusion. Using mucosal microcirculation as an in situ assay, cheek pouch tissue was exteriorized in anesthetized (phentobarbital 70 mg kg(-1) intraperitoneal) male hamsters (N=60) to observe the terminal feed arterioles (∼8 μm diameter) and the immediately upstream arcade arterioles (∼20 μm). Curcumin (10(-12)-10(-4) mol l(-1)) was applied dose-wise (micropipette, 60 seconds). Subnanomolar curcumin dilated, whereas micromolar doses constricted, the arterioles. For the terminal arteriole: vasodilation logEC(50) -10.3±0.2, peak dilation +39±1%; vasconstriction logEC(50) -8.0±0.4, peak constriction -14±2%. Simultaneous atropine (muscarinic antagonist) or PD142893 (endothelin antagonist) had no effect. Propranolol (β-adrenergic receptor (β-Ad) antagonist) enhanced constriction by removing the vasodilation response to curcumin. Phentolamine (α-adrenergic receptor (α-Ad) antagonist) enhanced dilation to curcumin by removing the vasoconstriction response. Thus, the curcumin vasomotor activity on microcirculation was α-Ad and β-Ad receptor-dependent and its net vasoactive effect was concentration- and time-dependent.

 

Thank you for the link.  You're right, it is a bit confusing and I have to admit a little above my head.  However, it sounds like you might be right that the high curcumin content is what's causing me problems.  I guess I could try taking half the amount of longvida (200 mg) and see how it effects me.  I think douglas labs sells it where there's only 200 mg of longvida in each capsule (plus some other stuff) and prohealth sells one called "body and joint" which combines 200 mg of longvida and 333 mg of boswellia (which might be a pretty good combo).    

[resveratrol_guy]

I'm currently taking 16 Longvida (Curcubrain) per day (6.4 grams). I'd like to get up to 50, but we'll see. So I'm posting here just to register the fact that I'm being a voluntary rat.

The details and rationale for this extreme regimen are in this post.

The first thing to point out is that while Longvida is an SSRI at low doses, it actually increases dopamine at high doses, if the rodent studies translate to humans. Based on my own experience, I'm confident that they do. At first, it made me quite exhausted and destroyed my ability to focus. But now it's quite the opposite.

Also, lipidated curcumin comes in a variety of forms, which have radically different pharmacokinetics. The data is provided in the video linked by David Ellis above.
 

Edited by resveratrol_guy, 01 June 2015 - 05:26 PM.

[resveratrol_guy]

For the record, I'm up to 20 Curcubrain pills (8 grams of Longvida) per day. I took 10 (5 in capsules, 5 in water) today within a 20-minute period. An hour later I was a feeling a bit woozy, probably due to the heavy disinflammation affect. But it was never a "sick" feeling, and I feel fine now. I was initially having a sore throat issue several days ago, but it's almost gone, so I suspect that Longvida was not to blame. Removing it from the gelcaps might also minimize any stomach issues (but in theory could cause more degradation due to stomach acid). In any event, I can't discern any toxic effects whatsoever.

 

I'm trying to gradually raise my dose to 50 pills a day, ideally taken within a matter of minutes. This would in theory put me around 2 uM in the plasma, which would cut my brain plaque load roughly in half in a month, if I'm anything like a rat. (Strictly speaking, I should probably take one pill at a time throughout the day, as incremental dosing of any drug always has diminishing effects. But the rat study only focussed on plasma concentration, so I'm planning on doing it by the book. Spiking the plasma also has the advantage of increasing the odds of killing tumor cells outright, as opposed to educating them about how to avoid curcumin.)

 

[PerfectSeek]

What does everyone think of Theracurmin?  This blog has a brief writeup comparing the bioavailabilities, but I'm not sure how accurate it is.  I've tried both BCM-95 and Thercurmin, and subjectively, Theracurmin is "cleaner" and reaches my brain better.  BCM-95 was a bit too strong for me, and appeared to be slightly axiogenic.  

 

http://truttmd.com/c...te-theracurmin/

 

 

[resveratrol_guy]

Brilliant post, PerfectSeek.

First of all, based on that blog by Dr. Trutt, it appears that this study shows that Longvida reaches some sort of weird saturation very rapidly: whereas 650 mg oral achieves 22 ng/mL peak plasma, 4000 mg merely achieves 41. I haven't been able to acquire the full text, but if this is accurate, then it suggests that anyone taking megadose Longvida (like me) would be better off spacing it throughout the day, steadily depleting brain plaque in tiny amounts, as opposed to attempting a huge plasma spike that probably isn't happening. (I'm a bit wary of the possibility that such protracted dosing might allow some aggressive tumor cells to survive, yet result in evolutionary pressure which eventually equips them with curcuminoid avoidance capability. But I can't worry about that theoretical risk. I need to minimize brain plaque.)

So for that reason, I'm impressed by Theracurcumin's pharmacokinetics, achieving about 270 ng/mL from a 2100 mg dose. Then again, their data is very noisy: a 1000 mg dose achieved only about a third of that peak plasma concentration, whereas in theory lower doses should be better absorbed, not worse. If the study were well controlled, they would have prevented food intake close to the plasma testing window. So I have some serious doubts about their methods, and frankly the veracity of the numbers to begin with. If nothing else, the 3-hour variance in achieving peak concentration suggests poor control of digestive factors if not plain old fraud. (Trutt makes the point that some of the graphs are from different studies, which could also explain the disconnect. Either way, it's hard to trust.)

Still, it would be a shame to dismiss a pivotal breakthrough in curcumin absorption just because sloppy experimental methods make the data look fake. So in addition to better controlled studies, I would be interested to hear your explanation of how Theracurcumin is "cleaner". Have you tried Longvida? (I've never tried Theracurcumin.)
 

Edited by resveratrol_guy, 06 June 2015 - 02:25 PM.

[resveratrol_guy]

I dug up some resources on Theracurmin (not "Theracurcumin", sorry). It looks like this may be a better (albeit moderately more expensive) form of curcumin than Longvida, although the science is poor as I mentioned above. Still, the water solubility test shown in this video is impressive; my Longvida just sits on the bottom of the glass. Here is the manufacturer's page for the higher concentrated variety, Theracurmin HP. According to this study, it achieves superior performance compared to Meriva (but so does Longvida). And there are Longecity threads here and here. I'm surprised that this does not seem to have garnered more attention here.

 

Crudely speaking, it looks like Longvida is optimized for cellular penetration (fat solubility), whereas Theracurmin is optimized to create impressive plasma concentrations (water solubility). Perhaps I should be taking both...

 

Edited by resveratrol_guy, 06 June 2015 - 04:16 PM.

[DeadMeat]

The problem with Theracurmin is that they, just like with things as MetaCurcumin, measured total curcumin(metabolite + if applicable free). Instead of just free curcumin(which you need if you want it in the brain). As mentioned in the Verdure Sciences video(around 16 min): some studies add B-glucuronidase that converts metabolite: curcumin glucuronide, back into free curcumin before measuring it.

Theracurmin bioavailability study:
https://www.jstage.j...5/34_5_660/_pdf

Sample Preparation A 0.1 ml aliquot of each plasma sample collected from rats and human subjects was transferred to a 10 ml glass tube and then 0.11 ml of 0.1M sodium acetate buffer (pH 5.0) containing 1000U B-glucuronidase was added. The resulting solutions were incubated to hydrolyze the curcumin conjugates at 37 °C for 1 h.

same with that comparison study of Theracurmin, BCM-95 and Meriva.
https://www.jstage.j...61/1/61_37/_pdf

Sample preparation and measurement of  plasma curcumin levels. Blood sample preparation and the measurement of plasma curcumin levels were previously reported (22, 30). Briefly, each plasma sample was incubated with 0.1 M sodium acetate buffer (pH 5.0) containing 1,000 U glucuronidase (Wako Pure Chemical Industries, Ltd., Japan) at 37 ̊C for 1 h to hydrolyze the curcumin conjugates.

[david ellis]

I bought a Revgenetics curcumin pump.   In the past, I used BCM95.   It worked well for me, I was able to control vision artifacts with one 750 mg gel a day.   At first, I was disappointed, no effect with one pump.   But,  I found effectiveness at 7-8 pumps a day.  Great, I will be able to slow things down. 

 

My eye surgeon told me on my April visit that macular degeneration was starting.   The official diagnosis says  you have macular degeneration if you have drusen.   He doesn't call it until he sees disruptions in the blood vessels.  Despite drusen,  my vision is still basically 20/20.   

 

Longvida has already proved that it's curcumin crosses the blood/brain barrier by photographing radioactive tagged Alzheimer's plaque inside the eyes.    My experience suggests that both BCM95 and Metacurcumin do cross also.

[APBT]

First of all, based on that blog by Dr. Trutt, it appears that this study shows that Longvida reaches some sort of weird saturation very rapidly: whereas 650 mg oral achieves 22 ng/mL peak plasma, 4000 mg merely achieves 41. I haven't been able to acquire the full text, 

 

FULL TEXT:

Attached Files

•  Safety and Pharmacokinetics of a Solid Lipid Curcumin Particle Formulation in Osteosarcoma Patients and Healthy Volunteers.pdf   813.31KB   13 downloads

[resveratrol_guy]

I just finished 35 Curcubrain pills (14 grams) over a 10-hour period, and apart from having been a bit tired and a bit thirsty today, I feel absolutely fine. There was no stomach upset or any other symptom of accute toxicity. For the record, I carefully poured all the pills into a glass, and drank it sip by sip, hour by hour. I believe I had at most 1% waste at the end of it.

 

@ DeadMeat: Good catch! IMO that's borderline fraud. I mean, what good is glucuronidated curcumin? So I'll stick with Longvida.

 

@ david ellis: I'm very sorry to hear about your eye problem. NGF eye drops come to mind, but they're expensive and hard to obtain. Yes, Longvida has been shown to disaggregate various amyloid and tau species to varying but clinically efficacious extents, at least in rodents. I'm naively hoping to repeat the same in my own brain.

 

@ APBT: SCORE! You helped me discover (Table 4 in your linked study) that Dr. Trutt's conclusion about Longvida's peak plasma concentration (Cmax) is correct but misleading. Yes, it's true that Cmax saturates rapidly with escalating dose. However, the integral of concentration over time (AUC, area under curve) is 189 units at 2000 mg and 375 units at 4000 mg -- right on the money if we hope for linear increase in AUC with increasing dose! In other words, total free curcumin exposure does exactly what we would hope, rather than to become increasingly impeded by the digestive system. Personally, I think AUC matters more than Cmax (with the tumor training caveat that I mentioned above). BTW it's interesting that this is not true at 650 mg vs. 2000 mg, in which case the AUC barely improves in the latter case; I suspect that a certain amount of curcumin gets consumed up front, perhaps as a result of blunting isolated instances of severe inflammation, after which prolonged intact circulation becomes possible.

 

Edited by resveratrol_guy, 07 June 2015 - 12:09 AM.

[resveratrol_guy]

Because I don't want to hijack this thread, but it may be of interest to some of you, I've begun my megadose Longvida journal here. This is my first day at 20 grams...

 

[katrina]

When I run out of my Doctor's Best Curcumin Phytosome Featuring Meriva Vegetarian Capsules, 500mg 180 Count, I was planning on buying Logvida.  But well, I get inexpensive Amazon products for reviews and got this for $1.  Who could pass that up ya know?  Turmeric Curcumin C3 with BioPerine Black Pepper Extract - 750mg per Capsule, 120 Veg. Capsules - GMO Free Tumeric, Standardized to 95% Curcuminoids for Maximum Potency.

 

Anyways a few days in, something odd happened.  Now I know curcurmin is supposed to help working memory, but I actually remembered something that happened 40 years ago, that I haven't even thought of for 40 years!  This makes me even more excited about trying Longvida.  Amazing isn't it?  It also says something about the Doctors best brand .  Blech....

[resveratrol_guy]

When I run out of my Doctor's Best Curcumin Phytosome Featuring Meriva Vegetarian Capsules, 500mg 180 Count, I was planning on buying Logvida.  But well, I get inexpensive Amazon products for reviews and got this for $1.  Who could pass that up ya know?  Turmeric Curcumin C3 with BioPerine Black Pepper Extract - 750mg per Capsule, 120 Veg. Capsules - GMO Free Tumeric, Standardized to 95% Curcuminoids for Maximum Potency.

 

Anyways a few days in, something odd happened.  Now I know curcurmin is supposed to help working memory, but I actually remembered something that happened 40 years ago, that I haven't even thought of for 40 years!  This makes me even more excited about trying Longvida.  Amazing isn't it?  It also says something about the Doctors best brand .  Blech....

 

First of all, I'm unsurprised by your enhanced longterm memory (and happy to have additional statistical weight). Apart from disinflammation, my mother and I have both observed the same. Specifically, it's longterm memory for specific events, places, or names, but generally not visual data. I suspect that this effect is a straightforward result of the disinflammation, and perhaps the SSRI aspects. The best parallel would be a weaker version of perispinal Etanercept. Based on my own research and experience, I agree that Longvida would be even better for you. Just beware that the seratonin effects (fatigue, mainly) will hit you hard for a week or so, or until you hit the putative dopamine threshold (8ish pills/day).
 

OTOH I do not believe that your memory improvement has anything to do with beta amyloid or tau disaggregation; that effect occurs at megadoses over a period of weeks, if the rodent studies translate to humans.

[APBT]

VRP has Longvida (60 - 500 mg caps) on sale for 50% off until midnight toady.  Use savings code V50CAA59 at checkout.  I believe everything on their website is 50% off as well; free shipping for orders over $99. 

http://www.vrp.com/longvida-60-caps

[katrina]

When I run out of my Doctor's Best Curcumin Phytosome Featuring Meriva Vegetarian Capsules, 500mg 180 Count, I was planning on buying Logvida. But well, I get inexpensive Amazon products for reviews and got this for $1. Who could pass that up ya know? Turmeric Curcumin C3 with BioPerine Black Pepper Extract - 750mg per Capsule, 120 Veg. Capsules - GMO Free Tumeric, Standardized to 95% Curcuminoids for Maximum Potency.

Anyways a few days in, something odd happened. Now I know curcurmin is supposed to help working memory, but I actually remembered something that happened 40 years ago, that I haven't even thought of for 40 years! This makes me even more excited about trying Longvida. Amazing isn't it? It also says something about the Doctors best brand . Blech....

First of all, I'm unsurprised by your enhanced longterm memory (and happy to have additional statistical weight). Apart from disinflammation, my mother and I have both observed the same. Specifically, it's longterm memory for specific events, places, or names, but generally not visual data. I suspect that this effect is a straightforward result of the disinflammation, and perhaps the SSRI aspects. The best parallel would be a weaker version of perispinal Etanercept. Based on my own research and experience, I agree that Longvida would be even better for you. Just beware that the seratonin effects (fatigue, mainly) will hit you hard for a week or so, or until you hit the putative dopamine threshold (8ish pills/day).

OTOH I do not believe that your memory improvement has anything to do with beta amyloid or tau disaggregation; that effect occurs at megadoses over a period of weeks, if the rodent studies translate to humans.

8 pills? Eeek... No way.....

My long term memory is better than most to begin with. I can remember being in a crib and many events around that time. Learned how to walk to get the heck out of diapers. Lol.... Threw stuffed toys out of my crib to annoy my family when they had to pick them all up. Thought my older sister was a stupid moron to be chewing on coins etc... Felt like an adult not being allowed to function as one.

That event I mentioned? I can recall all details including conversations that transpired over weeks. As always one to recall conversations a year or more later, folks often say, how do you do that?

Edited by katrina, 09 June 2015 - 10:02 PM.

[Chris Edited]

I was about to order more Longvida and decided to check on the most recent feedback about its use...   I was surpised to see no replies to this post .. it is definately enough to disuade me from relying on curcumin as a non NSAID, plant based anti-inflamatory..

 

We'll see if this study stands any repeating  but the conclusion certainly  conveys a high degree of confidence it the accuracy of the results which appear to me sufficient to suspend its use in this concentrated, high bioavailable formulation..

 

So what does everyone think of the implications of the following study?

 

http://www.ncbi.nlm....pubmed/25649709

 

 

...We have found that human vascular smooth muscle and endothelial cells derived from aorta are very sensitive to curcumin treatment and can senesce upon treatment with cytostatic doses. We observed characteristic senescence markers but the number of DNA damage foci decreased. Surprisingly, in vascular smooth muscle cell (VSMC) activation of DNA damage response pathway downstream of ataxia-telangiectasia mutated (ATM) was observed. ATM silencing and the supplementation of antioxidants, N-acetyl-L-cysteine (NAC) or trolox, did not reduce the number of senescent cells. Thus, we have shown that curcumin can induce senescence of cells building the vasculature, which is DNA damage and ATM independent and is not induced by increased reactive oxygen species (ROS) level. We postulate that an increase in the bioavailability of curcumin should be introduced very carefully considering senescence induction as a side effect.

 

 

Edited by Chris Edited, 16 June 2015 - 03:52 AM.