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> Increasing Bioavailability
KoolK3n
post May 07, 2012, 10:56 AM
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Are there any other ways of increasing absorption of turmeric (curcumin) besides bioperine?
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Flex
post May 07, 2012, 01:41 PM
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Keep an eye on Dr. Gary Small and Dr. Heber--that is exactly what they are working on. I believe they are working on a nano particle emulsion now, but there is nothing to say that that will increase how much actually makes it to your brain. Ultimately, it may not make a particle of difference if it crosses the blood brain barrier or not.

I recently had the idea to try to use a biochemistry technique (icing out) to try to increase the permeability of the blood brain barrier, but I really have no way of testing my hypothesis. Basically the idea would be to coadminister XYZ with a high dose of MSM in hopes that if you are able to attain even slightly higher than steady state equilibrium concentration for even a short period of time (less than 15 min) the MSM may temporarily increase the permeability of the BBB by making water appear more ice like (a more hydrophobic character). If it is true that there is a steady state equilibrium concentration difference of MSM across the membrane, this may serve to effectively shuttle hydrophobic molecules across the barrier by creating preferential entropic state on one side of the membrane vs. the other.

Dose it work? Who knows, but I have been taking mega doses of MSM for a few weeks now, and I appreciate the cost to benefit I have received very much. If it is true that what is good for the skin is good for the brain, then MSM ought to be the shit for brain health.

Just a thought smile.gif
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KoolK3n
post May 07, 2012, 03:45 PM
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Thanks! I'm gonna take MSM & bioperine in the evening to enhance absorption of curcumin and resveratrol. When more research becomes publicly available for newer efficient methods, I will consider adding pterostilbene (expensive).
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KoolK3n
post May 07, 2012, 05:14 PM
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Stupid question but would uncapsulating my 500mg resveratrol and mixing it into red wine make any difference? Also, I was gonna add 4mL of Astragalus with other drinks as well. Is that a bad idea since alcohol impairs nutrient absorption?
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Flex
post May 07, 2012, 06:17 PM
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QUOTE(KoolK3n @ May 07, 2012, 06:14 PM) *

Stupid question but would uncapsulating my 500mg resveratrol and mixing it into red wine make any difference? Also, I was gonna add 4mL of Astragalus with other drinks as well. Is that a bad idea since alcohol impairs nutrient absorption?


I think all of the research on resveratrol was an over hyping for the wine industries benefit that doesn't solve the French paradox wink.gif What is the answer? Who knows... I would guess calorie restriction. People in France may eat fatty food, but they are not fat asses like Americans.
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KoolK3n
post May 07, 2012, 08:22 PM
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Ethanol increases absorption of quercetin

Limited research suggests quercetin and/or olive oil increases absorption of other nutriets such as curcumin, etc..
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Flex
post May 07, 2012, 08:37 PM
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QUOTE(KoolK3n @ May 07, 2012, 09:22 PM) *

Ethanol increases absorption of quercetin

Limited research suggests quercetin and/or olive oil increases absorption of other nutriets such as curcumin, etc..


Lol well the point was sort of that ethanol is not a reasonable way to increase absorption smile.gif This is basically the idea behind my MSM theory. MSM serving as a sort of phase transfer catalyst in a sense (alright not really). The reason you need the oil and emulsifier, is because an emulsifier makes oil and water more miscible... All you are doing is helping to facilitate the transfer from one solvent to another. Great idea to use emulsifiers though--never crossed my mind.
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KoolK3n
post May 08, 2012, 05:04 AM
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QUOTE(Flex @ May 07, 2012, 11:37 PM) *

Lol well the point was sort of that ethanol is not a reasonable way to increase absorption smile.gif


Blarg! I should have clarified the link as, "Ethanol increases absorption of quercetin when intoxicated (drunk)?"

QUOTE(Flex @ May 07, 2012, 11:37 PM) *

This is basically the idea behind my MSM theory. MSM serving as a sort of phase transfer catalyst in a sense (alright not really).


I kinda understand, but I'm still confused with how MSM would act as a phase transfer catalyst for other substances.
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Flex
post May 08, 2012, 09:20 AM
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Haha sounds like a better clarification to me smile.gif That said, should you happen to be getting plastered anyhow, 1 oz of prevention may prove to be more like 1.0001 oz lol
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Flex
post May 08, 2012, 09:28 AM
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http://onlinelibrary.wiley.com/store/10.11...1z8dzgg0281f3ef

Not a phase transfer catalyst per say, but lets call it an "emulsifier" if you will (also not an accurate description wink.gif
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KoolK3n
post May 08, 2012, 09:33 AM
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QUOTE(Flex @ May 08, 2012, 12:20 PM) *

Haha sounds like a better clarification to me smile.gif That said, should you happen to be getting plastered anyhow, 1 oz of prevention may prove to be more like 1.0001 oz lol


By no means am I going to be using this as a plausible excuse for my drunkenness lol. Actually, I rarely get drunk when drinking. As with marijuana, I drink "smart". Beer and [red] wine is usually what I go with. I tend to avoid hard liquor.
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Flex
post May 08, 2012, 10:02 AM
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I tend to avoid it all together. I cannot stand the taste of alcohol, it just makes me think of solvents after being in a lab all day...
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KoolK3n
post May 08, 2012, 08:29 PM
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QUOTE(Flex @ May 08, 2012, 01:02 PM) *

I tend to avoid it all together. I cannot stand the taste of alcohol, it just makes me think of solvents after being in a lab all day...


I used to feel the same way about coffee (not really). But anyhow, I'm going to take any precautions I can such as maintaining my piracetam, artichoke, and silymarin consumption. Simply following Aubrey de Grey's advice lol.

http://en.wikipedia.org/wiki/File:Possible..._of_ethanol.svg

Side note, wine contains anthocyanidins which may promote Nrf2 expression.

Okay, so far here are all the methods on increasing bioavailability:
-Bioperine
-Edible Oil (Soybean, Olive, etc)
-MSM
-Quercetin w/bromelain

Three of which most people taking curcumin are unaware of, though bioperine yields the most absorption increase.
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Flex
post May 09, 2012, 04:52 AM
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These sort of things tend to work synergistically. I personally believe the health benefits from phytonutrients are from activation of our DNA, not by acting directly, and thus have no need to cross the blood brain barrier. All they have to do is be eaten and detoxified by our cytocrome p450s. I think each of these fat soluble toxins are important because they are all similar molecules but with slightly different modifications and forms that have evolved over time. They are fat soluble, and thus cannot be excreted as is, they must first be made water soluble. Hence, our bodies do just that. We use enzymes (made from DNA template, hence we need to modify our DNA to make it more accessible to transcribe more RNA) to tack on functional groups so that we can excrete these molecules, and we do it really well. In fact, most of them are only in circulation for 15 min of so I believe and basically irrelevant after an hour. Just as our genome evolved over time to accommodate each new threat, so too must our diet. We are most evolved to tackle those ancient threats like broccoli and Swiss chard. Modern threats (meat, dairy, refined grains) have been introduced too quickly and are not compatible in great abundance with our bodies, such as trans fats. That is not to say that at some point in the future, trans fats cannot be a healthy part of our diet--we are just not evolutionarily ready to handle that assault--we would need a few million years to prepare our defenses.
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KoolK3n
post May 09, 2012, 10:01 AM
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QUOTE(Flex @ May 09, 2012, 07:52 AM) *

These sort of things tend to work synergistically. I personally believe the health benefits from phytonutrients are from activation of our DNA, not by acting directly, and thus have no need to cross the blood brain barrier.


Yes! The important ones to pay attention to are Sirtuin, p16, p53, hTERTAGE, Nrf2, mTOR, NF-κB, etc. Vegetables/fruits/herbs have been theorized to promote healthy expressions of some of these genes, but the problem is that in order to reap strong therapeutic benefits requires gluttony of these nutrients and new methods on increasing bioavailability. Though any dietary consumption of these nutrients is strongly recommended.

http://lpi.oregonstate.edu/infocenter/phyt...lavonoids/#tab1
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Flex
post May 09, 2012, 03:21 PM
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Cytochrome p4502c19 is one you ought to get familiar with given your interest in nootropics. Let your quest begin! wink.gif

This little number here that they do not go into is the important one in my theory "stimulating phase II detoxification enzyme activity (19, 20): Phase II detoxification enzymes catalyze reactions that promote the excretion of potentially toxic or carcinogenic chemicals."

They themselves are not antioxidants, they just stimulate our bodies to create more of our own endogenous antioxidants through gene activation.
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KoolK3n
post May 11, 2012, 03:48 AM
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QUOTE(Flex @ May 09, 2012, 06:21 PM) *

Cytochrome p4502c19 is one you ought to get familiar with given your interest in nootropics. Let your quest begin! wink.gif


This is all I could find:

QUOTE(Flex @ Mar 07, 2011, 08:38 PM) *

Even more interesting is the fact that curcumin (which is found in tumeric) is a strong inhibitor of CYP2C19 (cytochrome P450 2C19) and has been shown very beneficial in the prevention of Alzheimer's. Deprenyl has been used to treat Alzheimer's.



QUOTE(Flex @ May 09, 2012, 06:21 PM) *

This little number here that they do not go into is the important one in my theory "stimulating phase II detoxification enzyme activity (19, 20): Phase II detoxification enzymes catalyze reactions that promote the excretion of potentially toxic or carcinogenic chemicals."


http://www.ncbi.nlm.nih.gov/pubmed/11768769?dopt=Abstract (19)
http://www.ncbi.nlm.nih.gov/pubmed/11950788?dopt=Abstract (20)

Are you suggesting taking the xenobiotics/flavonoids mentioned in the two links above shortly after a curcumin dose increases bioavailability? Ex: BHA, tBHQ, GTP, EGCG, PEITC, sulforaphane, acacetin, apigenin, luteolin, and diosmetin. Some of them are toxic so I am left with: tBHQ, EGCG, sulforaphane, apigenin, and luteolin..

Other synthetic drugs that also inhibit CYP2C19 coincidently have serious potential side-effects, most notably, aplastic anemia and respiratory infection...
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Flex
post May 11, 2012, 08:42 AM
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Very good you found it! Now look into the cytochromes that detoxify deprenyl, and think back to what Jakare mentioned about ingesting different forms of deprenyl. Why would the oral form be preferential to the sublingual form? When we take deprenyl orally, we see a greater concentration of amphetamine in the blood. But, if Jakare is right that the oral form offers greater protection against aging--seems counter intuitive right?

The pieces you will need to solve the puzzle:
Cholesterol synthesis pathway
Cytochrome p4502C19 connection to deprenyl (you got that one!)
What Cytochrome detoxifies deprenyl?
How are cholesterol and steroid hormones related?
What steroid hormone do you notice that also interacts with the deprenyl detox route?
What does this tell us about stress, the food we eat, and the meaning of life?

I could tell you my answer, but that doesn't get you anywhere now does it smile.gif Actually it doesn't get me anywhere either. In fact, we all benefit by me NOT telling you! Share with us whatever connections you might make yourself. They will certainly be different than my own, and will lend some new insight. Then I will share with you my views. You are getting close Ken, and the answer lies at the heart of our very existence--one might say, it is written in our DNA.
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KoolK3n
post May 11, 2012, 11:08 AM
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QUOTE(Flex @ May 11, 2012, 11:42 AM) *

Why would the oral form be preferential to the sublingual form? When we take deprenyl orally, we see a greater concentration of amphetamine in the blood. But, if Jakare is right that the oral form offers greater protection against aging--seems counter intuitive right?


Transdermal administration offered greatest bioavailability of deprenyl.
http://jcp.sagepub.com/content/47/10/1256.abstract

QUOTE(Flex @ May 11, 2012, 11:42 AM) *

The pieces you will need to solve the puzzle:
1. Cholesterol synthesis pathway
2. Cytochrome p4502C19 connection to deprenyl (you got that one!)
3. What Cytochrome detoxifies deprenyl?
4. How are cholesterol and steroid hormones related?
5. What steroid hormone do you notice that also interacts with the deprenyl detox route?
6. What does this tell us about stress, the food we eat, and the meaning of life?


1. ACTH? Point 5.
2. Yay
3. Cytochrome P4502B1 was knocked out after introduction of deprenyl:
http://dmd.aspetjournals.org/content/24/6/669.abstract
4. Nicotinamide adenine dinucleotide phosphate reduced form! NADPH!
5. ACTH. Deprenyl regulates it: http://en.wikipedia.org/wiki/Adrenocortico...ormone#Function
6. Isothiocyanates: http://www.ncbi.nlm.nih.gov/pubmed/11123978

As we age, neutrophils increase ROS (free radical) production but on the other hand lowering neutrophils may promote aplastic anemia. This may connect to the side-effects associated with strong cytochrome p4502C19 inhibitors. http://en.wikipedia.org/wiki/Neutrophil_gr...Role_in_disease

Deprenyl prevents deterioration of the substantia nigra.

I don't understand how this all relates..

QUOTE(Flex @ May 11, 2012, 11:42 AM) *

..the answer lies at the heart of our very existence--one might say, it is written in our DNA.


mtDNA mutations!!!!! http://www.ncbi.nlm.nih.gov/pubmed/16604074 Free-radicals induce mtDNA damage and mutations. Superoxide anions and hydrogen peroxide production increases with age. Counteract by amplifying superoxide dismutase, catalase, and glutathione peroxidase levels. Wait. No. Take a look here:
http://www.aapsj.org/view.asp?art=aapsj080362
SS peptides/MitoQ10?

Eureka! http://webcache.googleusercontent.com/sear...n&ct=clnk&gl=us
then
http://en.wikipedia.org/wiki/SkQ
No recent english articles have arisen in the past two years..
But there are in russian!!
http://serbian.ruvr.ru/2012_05_05/kompjuter-starenje/ (Translate it with google translator)
Tablets will be synthesized over the summer followed by animal tests.
For more information, search for it on RussiaToday.

So far here is all that we can use until these new antioxidant drugs are released:
-Vitamin E
-Ubiquinol
-Acetylcysteine
-SOD Catalase
-Acetyl-L-carnitine
-Lipoic acid
-PQQ
-Whey Protein
-Silymarin
-Pantethine (Not related)
-Creatine (Not related)
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Flex
post May 11, 2012, 10:11 PM
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You have found all of the pieces, but the most important one smile.gif I just found it myself. Our DNA is of the same essence as our most primitive ancestors. The only difference is we have evolved over time. Those forms which occurred far in the past are the most compatible with the essence of our being, because we have had the most time to adapt to them and learn from them. Modern pharmacology tricks the body. It is introducing new concepts that it is unfamiliar with, and not yet ready to handle. These modern threats are not threats at all, but part of our future being. The only problem is, we are not ready for them yet in the kinds of doses that people are being given.

Just as we shouldn't notice a true nootropic, we shouldn't notice the food we put in our bodies. If you feel sluggish you are doing something wrong. If you feel hyper, you are probably doing something wrong two. Life is the balance that occurs right in the middle. Look at NADPH! The ratio of NADPH/NADP+ never changes locally within the cell--it exists at a steady state "equilibrium." I put equilibrium in quotes, because equilibrium is the state we achieve at rest, but life isn't resting. It is flowing. The secret to the flow, is the point of balance between two opposites like NADPH/NADP+. It is this balance point that is like the hole in a wheel which allows it to move. Without the hole, the wheel does not spin.

What does all of this mean? Eat your fruits and veggies! We can stimulate all of the same pathways, but in a much more balanced way. Tread lightly with these new creations, it will be a while before they are fully evolved shall we say wink.gif I am glad you seem to have enjoyed the game. That is the real lesson. Your are growing your mind by seeking the answers. It is not the substances that are bringing forth your creative potential, it is the possibility of the future potential of these substances that has inspired you to learn. Let it drive your thirst for knowledge, but always remember that the secret to creation is within us all along--sometimes we just need a little help to see it. But once we have seen it, we must grow. We must abandon the tool and learn how to take care of our selves. It will be a while before this all sinks in, and that is just fine. After-all, it is the journey not the destination right?
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KoolK3n
post Jun 01, 2012, 05:17 AM
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QUOTE(Flex @ May 12, 2012, 01:11 AM) *

After-all, it is the journey not the destination right?


"Life isn't a destination - it's a journey. We all come upon unexpected curves and turning points, moutaintops and valleys. Everything that happens to us shapes who we are becoming. And in the adventure of each day, we discover the best in ourselves. As you journey through life, choose your destinations well, but do not hurry there. You will arrive soon enough. Wander the back roads and forgotten paths, keeping your destination in your heart like the fixed point of a compass. Seek out new voices, strange sights, and ideas foreign to your own.

Such things are riches for the soul.

And if, upon arrival, you find that your destination is not exactly as you had dreamed, do not be disappointed. Think of all you would have missed but for the journey there, and know that the true worth of your travels lies not in where you come to be at the journey's end, but in who you come to be along the way."

-Unknown
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