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Chronic use of common sedative [benzos] linked to Alzheimer's risk


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Dear Becks

 

I am so pleased you managed to do some of the work you need to do for winter coming. Not like me, lazing about in bed all day!!!  >:(  sometimes we can't be positive, we just struggle on. I am sorry you are so afraid and isolated but God is always there for sure. When I felt I had no strength left I used to get comfort from Footprints in the Sand.

The thought that I was being carried through the worst of times made them seem more bearable somehow. It gave me enough reassurance to keep going one day at a time.

 

http://www.poetseers.org/the-great-poets/misc-2/footprints-in-the-sand/

 

I did not know that Leone Lewis had recorded it. Must listen.

 

The star is still shining.

 

Hugs

 

LF  :smitten:

 

 

 

 

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I had read Footprints in the Sand many years ago.  I have a Poet's Corner I started on this forum and posted some of my fav. poems.  Had a horrendous day again.  Main sewer line backed up and there's raw sewage all over the back yard right outside my kitchen window.  Smells like raw sewage in here.  How can I have one positive thought when I have to deal with this kind of crap on a regular basis?  Worried it backing up my line into my home. Looking out my kitchen window with raw sewage all over the grass?  Had to beg with the park manager to clean it up tomorrow.  Who knows if he will and I'll have to look at it forever.  I won't touch it.  had to clean up raw sewage at least two other times here where I live.  Once under my home in the summer and I had tons of flies and had to put lime down.  Then I was so sick and had to get the lawn mowed and drive to get money and I'm afraid of driving and thought I would puke from the sewage stench.  I'm all alone here and no one to help me or take care of things.  I'm running out of food and my friend didn't get to the store yet, he doesn't have time.  How do I keep a positive attitude when I'm starving to death and isolated here?  Hyperacusis is so bad I feel like I'll vomit from all the noise.  I don't have time to work on positive thoughts.  Woke up with intrusives about all the ppl. who have abused me all my life, couldn't stop it.
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Becksblue,  this same thing happened to one of my Facebook friends and they sued the city and received a $42,000 settlement.  Have you considered contacting a lawyer about this sewage problem?

Molly :smitten:

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Hello Becks

 

That is truly awful.  I am so sorry you have to endure all this.

 

It would be very hard to have any positive thoughts in that situation.

 

I hope your friend can get your groceries. I am sure he won't let you starve.

 

Hugs

 

LF

 

 

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It could be a case of reverse causation, but consider this:

 

- The longer your exposure to benzos, the higher your risk of Alzheimer's.  According to Harvard Health, "taking the drug for three to six months raised the risk of developing Alzheimer’s by 32%, and taking it for more than six months boosted the risk by 84%."

 

- Longer-acting benzos like Valium and Klonopin carry a greater risk than short-acting ones (Xanax, Ativan). 

 

This study seems to only focus on the elderly.  My question is whether younger people also see an increased risk of dementia down the road after using benzos. 

 

Note:  I'm not trying to be alarmist or suggest that we're all doomed.  Not at all.  Just think this is an important issue for many reasons.  Dr. Ashton says there's no reason to believe the damage from benzos is permanent so I remind myself of this frequently.

 

 

 

 

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Hi Benzo

 

It is not clear what the reason is for the correlation. Correlation and causation are not the same. Causation has absolutely not been proven. It may be that patients on benzos have some other factor in common which increases the likelihood of Alzheimer's.

 

Prof Ashton said there was no evidence to show structural damage.  I presume that is damage to the physical structure of the brain. She was not studying elderly patients.

 

LF

 

 

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All the studies I've read see an ASSOCIATION but they haven't determined if benzo's cause the dementia.  I read a study somewhere that asked if a person had ever taken benzo's in their life and the study found a 60 percent association betwee benzo's and dementia in that study.  I believe it was done in France in the 70's?  Not sure where that stat on whether a person ever took benzo's is, what the percentage was for that question.  It was a very old study and has been considered to be flawed.
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Here's an interesting study to go along with it:

 

http://www.nature.com/nm/journal/v20/n8/full/nm.3639.html

 

Summary:  It says that overproduction of GABA--the same neurotransmitter affected by benzos--is responsible for memory loss in Alzheimer's.  Still doesn't explain how benzos might actually CAUSE Alzheimer's (if that's even the case), but it's interesting nonetheless. 

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Here's an interesting study to go along with it:

 

http://www.nature.com/nm/journal/v20/n8/full/nm.3639.html

 

Summary:  It says that overproduction of GABA--the same neurotransmitter affected by benzos--is responsible for memory loss in Alzheimer's.  Still doesn't explain how benzos might actually CAUSE Alzheimer's (if that's even the case), but it's interesting nonetheless.

 

Hiya Benzodiazepunk.  Even if there isn't a causal relationship, it's possible that the additional burden of any benzodiazepine damage could unmask and make visible other cognitive problems at an earlier stage than if there had been no benzo damage.

 

 

 

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Hi Benzo

 

It is not clear what the reason is for the correlation. Correlation and causation are not the same. Causation has absolutely not been proven. It may be that patients on benzos have some other factor in common which increases the likelihood of Alzheimer's.

 

Prof Ashton said there was no evidence to show structural damage.  I presume that is damage to the physical structure of the brain. She was not studying elderly patients.

 

LF

 

Ashton's claim that there was no such evidence may stem from the fact that this has not been examined systematically in the post-mortem brains of human benzo patients. If this is true, then it paints quite a different picture as opposed to if her claim stemmed from studies that did examine whether structural damage had occurred, found it didn't in a large enough patient population, and concluded as such. Most people who pass away don't donate their brains for scientific research which would be required for such a conclusion to be made. Non-invasive imaging modalities (PET, MRI, etc) can potentially identify damage in-life (doesnt require autopsy), but these methods are not nearly as sensitive as histopathology of brain sections which is the best way to confirm/reject the benzo-damage hypothesis.  :)

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Researchers can do a biopsy of our other nerves affected by these benzo's rather than our brains while we're still alive.  Glutamate is created from GABA.  Wonder how that works with too much GABA. 
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Something's my that jumped out at me were the comments on the article listed in the nyt's. They were pro benzo by about 4-1.  Most people's were saying they would take the side effects for quality of life. No one expects them to turn on you like they did us. All the pain and none of the benefits. Future bb unfortunately.

 

 

I also believe while I will heal and function much better that there is some long term damage done to me.  This whole experience is so crushing and long, how can it not?  Not worth worrying about because nothing's no I can do.

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The comments after the NYT article are very interesting!

 

Yes, the comments are very interesting. It is somewhat validating to read that benzo users/ex-benzo users from realms other than BB (NYT readers), also experience horrific wd sxs that may last a very long time. i.e. that we here at BB are not a crazy bunch out on the fringe.  :)

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  • 2 weeks later...
  • 3 weeks later...

I posted this info on another thread but thought it may be helpful to also post it here. :)

 

 

As far as other supplements go- I did some digging after hearing about the increased risk for Alzheimer’s disease (AD) and here is what I came up with.

 

There are cells that perform housekeeping in your brain called Microglia.  They are a type of macrophage that is part of your brain’s immune system.  Microglia are constantly scavenging the Central Nervous system (CNS) for plaques, damaged neurons and infectious agents. (24) They literally engulf and digest cellular debris, foreign substances, microbes, and cancer cells in a process called phagocytosis. (5)  One of the things they digest are Amyloid Beta proteins, which are the same proteins that form the plaques in Alzheimer’s disease (AD).  In fact some scientists are looking at possible malfunction of microglia as one of the possible causalities of AD. (25)

 

Scientists have found that certain elements of our diet may aid Microglia to function properly.  These are omega-3 fatty acid DHA (docosahexaenoic acid) (6), Vitamin D3 (6,7), and Curcumin (7,25).

 

Another avenue being looked at in AD pathology is oxidative stress.  Scientists are investigating the potential antioxidant benefits of curcumin and melatonin in combatting oxidative stress. [8]  Interestingly, benzodiazepines have been shown to suppress melatonin levels.(9, 10)  Whether that has any significance in the benzo associated increased risk for AD remains to be determined.

 

Dietary antioxidants help neutralize oxidative stress so it is always beneficial to eat a diet rich in antioxidants.

 

Researchers have also made an association between elevated cortisol levels and AD (11, 12).  Whether or not benzo induced HPA Axis dysregulation may factor into this is unknown.

 

 

In any case the study that was recently published in the BMJ regarding benzos and a higher risk for AD (17) has influenced my thinking regarding supplements.  In my mind that news shifted the benefit to risk ratio in favor of taking a few supplements for potential AD prevention.

 

 

Vitamin D3

There is research showing that if you decide to take vitamin D3 it may be a good idea to also take vitamin K2.  I thought Mercola explained this relationship in pretty simple terms:

 

Vitamins D and K: 'The Gatekeeper and the Traffic Cop'

 

One of the undisputed benefits vitamin D provides for you is improved bone development by helping you ABSORB calcium. This is not news -- we have known about vitamin D and the absorption of calcium for many decades.

But there is new evidence that it is the vitamin K (specifically, vitamin K2) that directs the calcium to your skeleton, while preventing it from being deposited where you don't want it -- i.e., your organs, joint spaces, and arteries. A large part of arterial plaque consists of calcium deposits (atherosclerosis), hence the term "hardening of the arteries."

Vitamin K2 activates a protein hormone called osteocalcin, produced by osteoblasts, which is needed to bind calcium into the matrix of your bone. Osteocalcin also appears to help prevent calcium from depositing into your arteries.

You can think of vitamin D as the gatekeeper, controlling who gets in, and vitamin K as the traffic cop, directing the traffic to where it needs to go.

Lots of traffic -- but no traffic cop -- means clogging, crowding, and chaos everywhere!

In other words, without the help of vitamin K2, the calcium that your vitamin D so effectively lets in might be working AGAINST you – by building up your coronary arteries rather than your bones.

There is even evidence that the safety of vitamin D is dependent on vitamin K, and that vitamin D toxicity (although very rare with the D3 form) is actually caused by vitamin K2 deficiency. (13)

 

You can get Vitamin K1 through diet- your body can convert vitamin K1 into K2. (14)  Foods that are high in Vitamin K1 are dark leafy greens like kale and spinach.

 

Since I have little time to get enough sunlight exposure I decided to take Thorne Research D/K2 Drops.  I used the dosage guidelines set up by the Vitamin D Council here:

 

http://www.vitamindcouncil.org/about-vitamin-d/how-do-i-get-the-vitamin-d-my-body-needs/#

 

BTW- that is a great article and definitely worth taking the time to read.

 

Curcumin

Curcumin has always been known for poor absorption.  In order to increase absorption manufacturers have traditionally added piperine- however studies have shown that piperine modulates the GABA A Receptor. (18)  Thorne Research developed a formula with phosphatidylcholine to improve bioavailability which they called Meriva- however phosphatidylcholine may increase Acetylcholine levels in the brain (19) and may promote cardiovascular disease. (21)

 

Instead of trying to develop synthetic means of improving absorption, a group of scientists went back to the turmeric plant using the whole foods concept.  This view takes into account that generally plants will contain the necessary cofactors that promote bioavailability and utilization of their nutrients.  Taking advantage of the synergism between the sesquiterpenoids present in turmeric and the curcuminoid, they reconstituted curcumin with the non-curcuminoid components of the turmeric plant and found this combination increased the bioavailability substantially.  They called this new formulation BCM-95. (20)

 

Curcumin may also help lower inflammation because like NSAIDs it inhibits an inflammation causing enzyme known as COX-2.  Most NSAIDs also inhibit the beneficial enzyme COX-1 which protects the lining of the digestive tract and may therefore lead to ulcers. (22, 23)  Curcumin however does not inhibit COX-1 so it may be a safer alternative. (22)

 

The form of Curcumin with BCM-95 I take is made by Life Extension Super and is called Super Bio-Curcumin. I take it at the very beginning of a large meal to avoid stomach upset.  I had a little reflux for the first ten days until my body adjusted to it- which went away and now I get zero reflux.

 

I do not take fish oil capsules as I am pretty sure that I get enough omega 3 in my diet through grass fed beef and organic cage free eggs- plus I also eat fish on occasion.

 

Magnesium

I have also added an ionic form of magnesium to my regime.  I did this because I have read that much of our soil is depleted of nutrients which can make it difficult to get adequate intake.  The typical American diet consisting of white flour and processed foods may be sorely lacking magnesium as well.

 

The main reason I decided to take magnesium is because cells need it to produce Adenosine triphosphate (ATP), which provides energy to the cells so they can do their work.  ATP levels may also be affected in AD. (28)

 

I chose to take an ionic form of magnesium because it is easily absorbed and therefore is less likely to cause diarrhea.  It also makes it easier to divide doses so I can take it throughout the day.  I use a dropper and mix it into drinks.  The one I use is made by Good State.

 

Some people have said that they notice a revving of symptoms after starting magnesium supplementation.  Perhaps this is due to the involvement with ATP or maybe they coincidentally experienced a wave.  Carolyn Dean M.D., N.D.- the author of the book “The Magnesium Miracle” has a section in her book entitled “WHEN MAGNESIUM MAKES ME WORSE” where she discusses possible reasons why some people might feel worse after taking magnesium.  Her reasons as to why this may happen include: Not taking enough magnesium or taking too much, interactions with heart or thyroid medications, taking too much Vitamin D or calcium…to name a few. (26)

 

It is important to note that Dr. Dean also warns that people with any of the following conditions should avoid taking magnesium: kidney failure, myasthenia gravis, excessively slow hear rate, bowel obstruction. (26)

 

A word of caution for anyone thinking about using magnesium oils that are applied directly to the skin.  Applying magnesium oil to your skin may stimulate production of DHEA. (26)  This may potentially cause problems for people coming off benzos as DHEA acts a negative allosteric modulator (NAM) of the GABAAR (27), which means it reduces the effect of GABA.  It is also acts as a Positive Allosteric Modulator (PAM) of the NMDA receptor (NMDAR), which means it enhances the modulation of NMDARs.  Obviously, this would be the exact opposite effect one would desire while recovering from benzos.

 

 

 

1) Bacopa Monnieri

https://en.wikipedia.org/wiki/Bacopa_monnieri#Pharmacology

2) Acetylcholinesterase

https://en.wikipedia.org/wiki/Acetylcholinesterase

 

3) Sarin

https://en.wikipedia.org/wiki/Sarinhttps://en.wikipedia.org/wiki/Sarin

 

4) Choline acetyltransferase

https://en.wikipedia.org/wiki/Choline_acetyltransferase

 

5) Macrophages

https://en.wikipedia.org/wiki/Macrophage

 

6) Vitamin D, omega-3 may help clear amyloid plaques found in Alzheimer's

Rachel Champeau

UCLA Newsroom February 5, 2013

http://newsroom.ucla.edu/releases/vitamin-d-omega-3-may-help-clear-242465

 

7) Scientists pinpoint how vitamin D may help clear amyloid plaques found in Alzheimer's

Rachel Champeau

UCLA Newsroom March 6, 2012

http://newsroom.ucla.edu/releases/scientists-pinpoint-how-vitamin-229702

 

8] The redox chemistry of the Alzheimer's disease amyloid beta peptide.

Smith DG, Cappai R, Barnham KJ.

Biochim Biophys Acta. 2007 Aug;1768[8]:1976-90. Epub 2007 Feb 9.

http://www.sciencedirect.com/science/article/pii/S0005273607000387

 

9) Alterations to plasma melatonin and cortisol after evening alprazolam administration in humans.

McIntyre IM, Norman TR, Burrows GD, Armstrong SM.

Chronobiol Int. 1993 Jun;10(3):205-13. PMID:8319319

https://www.ncbi.nlm.nih.gov/pubmed/8319319

 

10) Suppression of plasma melatonin by a single dose of the benzodiazepine alprazolam in humans.

McIntyre IM, Burrows GD, Norman TR.

Biol Psychiatry. 1988 May;24(1):108-12. PMID:3370271

https://www.ncbi.nlm.nih.gov/pubmed/3370271

 

11) Stress and its influence on Alzheimer’s disease

UCIrvine Institute for Memory Impairments and Neurological Disorders (UCI MIND)- a National Institutes of Health (NIH) designated Alzheimer's Disease Research Center (ADRC)

http://www.mind.uci.edu/stress-and-its-influence-on-alzheimer%E2%80%99s-disease/

 

12) Modeling Alzheimer’s Disease

UCIrvine Institute for Memory Impairments and Neurological Disorders (UCI MIND)- a National Institutes of Health (NIH) designated Alzheimer's Disease Research Center (ADRC)

http://www.mind.uci.edu/research/cutting-edge-alzheimers-research/modeling-alzheimers-disease/

 

13) Vitamin K: The Missing Nutrient to Blame for Heart Attacks and Osteoporosis (Nope - NOT Calcium or Vitamin D)

Dr. Mercola

Health Articles, March 26, 2011

http://articles.mercola.com/sites/articles/archive/2011/03/26/the-delicate-dance-between-vitamins-d-and-k.aspx

 

14) Dr. Cannell on vitamin K2

John Cannell MD

Vitamin D Counsel November 27, 2013

http://www.vitamindcouncil.org/blog/dr-cannell-on-vitamin-k2/#

 

15) Organophosphate

https://en.wikipedia.org/wiki/Organophosphate

 

16) Acetylcholinesterase inhibitor

https://en.wikipedia.org/wiki/Acetylcholinesterase_inhibitor

 

17) Benzodiazepine use and risk of Alzheimer’s disease: case-control study

Billioti de Gage S, Moride Y, Ducruet T, Kurth T, Verdoux H, Tournier M, Pariente A, Bégaud B.

BMJ. 2014 Sep 9;349:g5205. doi: 10.1136/bmj.g5205.

PMID: 25208536

http://www.bmj.com/content/349/bmj.g5205

 

18) Efficient modulation of γ-aminobutyric acid type A receptors by piperine derivatives.

Schöffmann A, Wimmer L, Goldmann D, Khom S, Hintersteiner J, Baburin I, Schwarz T, Hintersteininger M, Pakfeifer P, Oufir M, Hamburger M, Erker T, Ecker GF, Mihovilovic MD, Hering S.

J Med Chem. 2014 Jul 10;57(13):5602-19. doi: 10.1021/jm5002277. Epub 2014 Jun 27. PMID:24905252

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106271/pdf/jm5002277.pdf

 

19) Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia.

Chung SY, Moriyama T, Uezu E, Uezu K, Hirata R, Yohena N, Masuda Y, Kokubu T, Yamamoto S.

J Nutr. 1995 Jun;125(6):1484-9. PMID:7782901

http://jn.nutrition.org/content/125/6/1484.full.pdf

 

20) A Pilot Cross-Over Study to Evaluate Human Oral Bioavailability of BCM-95CG (Biocurcumax), A Novel Bioenhanced Preparation of Curcumin.

Antony B, Merina B, Iyer VS, Judy N, Lennertz K, Joyal S.

Indian J Pharm Sci. 2008 Jul-Aug;70(4):445-9. doi: 10.4103/0250-474X.44591. PMID:20046768

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792534/

 

21) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease.

Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL.

Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922. PMID:21475195

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086762/

 

22) Curcumin The 21st Century Cure

Jan McBarron, M.D., N.D.

Too Your Health Books, 2012 ISBN: 978-0-9815818-9-7

 

23) Gastrointestinal and Cardiovascular Risk of Nonsteroidal Anti-inflammatory Drugs

Abdulwahed Al-Saeed

Oman Med J. 2011 November; 26(6): 385–391. doi: 10.5001/omj.2011.101

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251190/pdf/OMJ-D-10-00068.pdf

 

24) Microglia

https://en.wikipedia.org/wiki/Microglia

 

25) Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcumin.

Fiala M, Liu PT, Espinosa-Jeffrey A, Rosenthal MJ, Bernard G, Ringman JM, Sayre J, Zhang L, Zaghi J, Dejbakhsh S, Chiang B, Hui J, Mahanian M, Baghaee A, Hong P, Cashman J.

Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12849-54. Epub 2007 Jul 24. PMID:17652175

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1937555/pdf/zpq12849.pdf

 

26) The Magnesium Miracle

Carolyn Dean MD ND

Ballantine Books, NY 2014

ISBN: 978-0-345-49458-0

 

27) Dehydroepiandrosterone

Mechanism of Action

Wikipedia the free encyclopedia

https://en.wikipedia.org/wiki/Dehydroepiandrosterone

 

28) Characterization of ATP Alternations in an Alzheimer's Disease Transgenic Mouse Model.

Zhang C, Rissman RA, Feng J.

J Alzheimers Dis. 2014 Sep 26. [Epub ahead of print] PMID:25261448

http://www.ncbi.nlm.nih.gov/pubmed/25261448

 

 

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Thanks Perserverence,

 

Well written and well referenced post. Certainly, the animal studies help to establish proof of concept, but until we can empirically test some of these hypotheses in human, we should be cautious (as you were) in precociously drawing conclusions about the physiologic role/effect of these compounds in man.  :)

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Curcumin

Curcumin has always been known for poor absorption.  In order to increase absorption manufacturers have traditionally added piperine- however studies have shown that piperine modulates the GABA A Receptor. (18)  Thorne Research developed a formula with phosphatidylcholine to improve bioavailability which they called Meriva- however phosphatidylcholine may increase Acetylcholine levels in the brain (19) and may promote cardiovascular disease. (21)

 

Instead of trying to develop synthetic means of improving absorption, a group of scientists went back to the turmeric plant using the whole foods concept.  This view takes into account that generally plants will contain the necessary cofactors that promote bioavailability and utilization of their nutrients.  Taking advantage of the synergism between the sesquiterpenoids present in turmeric and the curcuminoid, they reconstituted curcumin with the non-curcuminoid components of the turmeric plant and found this combination increased the bioavailability substantially.  They called this new formulation BCM-95. (20)

 

Curcumin may also help lower inflammation because like NSAIDs it inhibits an inflammation causing enzyme known as COX-2.  Most NSAIDs also inhibit the beneficial enzyme COX-1 which protects the lining of the digestive tract and may therefore lead to ulcers. (22, 23)  Curcumin however does not inhibit COX-1 so it may be a safer alternative. (22)

 

The form of Curcumin with BCM-95 I take is made by Life Extension Super and is called Super Bio-Curcumin. I take it at the very beginning of a large meal to avoid stomach upset.  I had a little reflux for the first ten days until my body adjusted to it- which went away and now I get zero reflux.

 

Terrific post Perserverance! I really appreciate all the time you put in to writing up your articles!

 

Re curcumin - How come you don't just take it in as a whole food as the way to get your curcumin? Turmeric is not expensive. I throw a 3/4 inch piece into my protein shake every day and it doesn't really effect the taste of my shake. The Whole Foods here in San Francisco always seems to have it. I have been putting in a little ground pepper to help with the bioavailability but I guess I don't need to do that. I'm not exactly sure what the implications are of it modulating the GABA A receptor.

 

I had also read recently in Science Daily that another compound in turmeric (ar-turmerone) enhances the regeneration of the stem cells of the brain: http://www.sciencedaily.com/releases/2014/09/140925205819.htm

 

Kris

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Curcumin

Curcumin has always been known for poor absorption.  In order to increase absorption manufacturers have traditionally added piperine- however studies have shown that piperine modulates the GABA A Receptor. (18)  Thorne Research developed a formula with phosphatidylcholine to improve bioavailability which they called Meriva- however phosphatidylcholine may increase Acetylcholine levels in the brain (19) and may promote cardiovascular disease. (21)

 

Instead of trying to develop synthetic means of improving absorption, a group of scientists went back to the turmeric plant using the whole foods concept.  This view takes into account that generally plants will contain the necessary cofactors that promote bioavailability and utilization of their nutrients.  Taking advantage of the synergism between the sesquiterpenoids present in turmeric and the curcuminoid, they reconstituted curcumin with the non-curcuminoid components of the turmeric plant and found this combination increased the bioavailability substantially.  They called this new formulation BCM-95. (20)

 

Curcumin may also help lower inflammation because like NSAIDs it inhibits an inflammation causing enzyme known as COX-2.  Most NSAIDs also inhibit the beneficial enzyme COX-1 which protects the lining of the digestive tract and may therefore lead to ulcers. (22, 23)  Curcumin however does not inhibit COX-1 so it may be a safer alternative. (22)

 

The form of Curcumin with BCM-95 I take is made by Life Extension Super and is called Super Bio-Curcumin. I take it at the very beginning of a large meal to avoid stomach upset.  I had a little reflux for the first ten days until my body adjusted to it- which went away and now I get zero reflux.

 

Terrific post Perserverance! I really appreciate all the time you put in to writing up your articles!

 

Re curcumin - How come you don't just take it in as a whole food as the way to get your curcumin? Turmeric is not expensive. I throw a 3/4 inch piece into my protein shake every day and it doesn't really effect the taste of my shake. The Whole Foods here in San Francisco always seems to have it. I have been putting in a little ground pepper to help with the bioavailability but I guess I don't need to do that. I'm not exactly sure what the implications are of it modulating the GABA A receptor.

 

I had also read recently in Science Daily that another compound in turmeric (ar-turmerone) enhances the regeneration of the stem cells of the brain: http://www.sciencedaily.com/releases/2014/09/140925205819.htm

 

Kris

 

Hi Kris,

 

I am all about whole food…I think what you are doing with fresh turmeric is great.  I take the pill form for convenience (usually I am less lazy about such things  :laugh:).  The BCM-95 curcumin, which is the kind I take, contains ar-turmerone:

 

” Essential Oils used in BCM-95 are extracted using double steam distillation. Contents of Essential Oils are 7-9% with ar-tumerone,α-tumerone and β-tumerone around 50%.”

http://www.bcm95.com/abouts.html

 

Apparently ar-turmerone is found in the essential oils of the rhizomes:

 

“Essential Oils are found naturally in turmeric rhizomes and have been often used for flavoring and coloring purposes. Essential Oils constitutes of various molecules such as ar-tumerone, α-tumerone, β-tumerone, etc”

http://www.bcm95.com/Natural-Extracts.html

 

Here is a pic from Wikipedia of the turmeric rhizome in case anyone is wondering:

 

http://upload.wikimedia.org/wikipedia/commons/thumb/5/5b/Curcuma_longa_roots.jpg/300px-Curcuma_longa_roots.jpg

 

Stem cells may be hugely important when it comes to neurodegenerative diseases.  Thanks for the information.  :thumbsup:

 

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I posted this info on another thread but thought it may be helpful to also post it here. :)

 

 

As far as other supplements go- I did some digging after hearing about the increased risk for Alzheimer’s disease (AD) and here is what I came up with.

 

There are cells that perform housekeeping in your brain called Microglia.  They are a type of macrophage that is part of your brain’s immune system.  Microglia are constantly scavenging the Central Nervous system (CNS) for plaques, damaged neurons and infectious agents. (24) They literally engulf and digest cellular debris, foreign substances, microbes, and cancer cells in a process called phagocytosis. (5)  One of the things they digest are Amyloid Beta proteins, which are the same proteins that form the plaques in Alzheimer’s disease (AD).  In fact some scientists are looking at possible malfunction of microglia as one of the possible causalities of AD. (25)

 

Scientists have found that certain elements of our diet may aid Microglia to function properly.  These are omega-3 fatty acid DHA (docosahexaenoic acid) (6), Vitamin D3 (6,7), and Curcumin (7,25).

 

Another avenue being looked at in AD pathology is oxidative stress.  Scientists are investigating the potential antioxidant benefits of curcumin and melatonin in combatting oxidative stress. [8]  Interestingly, benzodiazepines have been shown to suppress melatonin levels.(9, 10)  Whether that has any significance in the benzo associated increased risk for AD remains to be determined.

 

Dietary antioxidants help neutralize oxidative stress so it is always beneficial to eat a diet rich in antioxidants.

 

Researchers have also made an association between elevated cortisol levels and AD (11, 12).  Whether or not benzo induced HPA Axis dysregulation may factor into this is unknown.

 

 

In any case the study that was recently published in the BMJ regarding benzos and a higher risk for AD (17) has influenced my thinking regarding supplements.  In my mind that news shifted the benefit to risk ratio in favor of taking a few supplements for potential AD prevention.

 

 

Vitamin D3

There is research showing that if you decide to take vitamin D3 it may be a good idea to also take vitamin K2.  I thought Mercola explained this relationship in pretty simple terms:

 

Vitamins D and K: 'The Gatekeeper and the Traffic Cop'

 

One of the undisputed benefits vitamin D provides for you is improved bone development by helping you ABSORB calcium. This is not news -- we have known about vitamin D and the absorption of calcium for many decades.

But there is new evidence that it is the vitamin K (specifically, vitamin K2) that directs the calcium to your skeleton, while preventing it from being deposited where you don't want it -- i.e., your organs, joint spaces, and arteries. A large part of arterial plaque consists of calcium deposits (atherosclerosis), hence the term "hardening of the arteries."

Vitamin K2 activates a protein hormone called osteocalcin, produced by osteoblasts, which is needed to bind calcium into the matrix of your bone. Osteocalcin also appears to help prevent calcium from depositing into your arteries.

You can think of vitamin D as the gatekeeper, controlling who gets in, and vitamin K as the traffic cop, directing the traffic to where it needs to go.

Lots of traffic -- but no traffic cop -- means clogging, crowding, and chaos everywhere!

In other words, without the help of vitamin K2, the calcium that your vitamin D so effectively lets in might be working AGAINST you – by building up your coronary arteries rather than your bones.

There is even evidence that the safety of vitamin D is dependent on vitamin K, and that vitamin D toxicity (although very rare with the D3 form) is actually caused by vitamin K2 deficiency. (13)

 

You can get Vitamin K1 through diet- your body can convert vitamin K1 into K2. (14)  Foods that are high in Vitamin K1 are dark leafy greens like kale and spinach.

 

Since I have little time to get enough sunlight exposure I decided to take Thorne Research D/K2 Drops.  I used the dosage guidelines set up by the Vitamin D Council here:

 

http://www.vitamindcouncil.org/about-vitamin-d/how-do-i-get-the-vitamin-d-my-body-needs/#

 

BTW- that is a great article and definitely worth taking the time to read.

 

Curcumin

Curcumin has always been known for poor absorption.  In order to increase absorption manufacturers have traditionally added piperine- however studies have shown that piperine modulates the GABA A Receptor. (18)  Thorne Research developed a formula with phosphatidylcholine to improve bioavailability which they called Meriva- however phosphatidylcholine may increase Acetylcholine levels in the brain (19) and may promote cardiovascular disease. (21)

 

Instead of trying to develop synthetic means of improving absorption, a group of scientists went back to the turmeric plant using the whole foods concept.  This view takes into account that generally plants will contain the necessary cofactors that promote bioavailability and utilization of their nutrients.  Taking advantage of the synergism between the sesquiterpenoids present in turmeric and the curcuminoid, they reconstituted curcumin with the non-curcuminoid components of the turmeric plant and found this combination increased the bioavailability substantially.  They called this new formulation BCM-95. (20)

 

Curcumin may also help lower inflammation because like NSAIDs it inhibits an inflammation causing enzyme known as COX-2.  Most NSAIDs also inhibit the beneficial enzyme COX-1 which protects the lining of the digestive tract and may therefore lead to ulcers. (22, 23)  Curcumin however does not inhibit COX-1 so it may be a safer alternative. (22)

 

The form of Curcumin with BCM-95 I take is made by Life Extension Super and is called Super Bio-Curcumin. I take it at the very beginning of a large meal to avoid stomach upset.  I had a little reflux for the first ten days until my body adjusted to it- which went away and now I get zero reflux.

 

I do not take fish oil capsules as I am pretty sure that I get enough omega 3 in my diet through grass fed beef and organic cage free eggs- plus I also eat fish on occasion.

 

Magnesium

I have also added an ionic form of magnesium to my regime.  I did this because I have read that much of our soil is depleted of nutrients which can make it difficult to get adequate intake.  The typical American diet consisting of white flour and processed foods may be sorely lacking magnesium as well.

 

The main reason I decided to take magnesium is because cells need it to produce Adenosine triphosphate (ATP), which provides energy to the cells so they can do their work.  ATP levels may also be affected in AD. (28)

 

I chose to take an ionic form of magnesium because it is easily absorbed and therefore is less likely to cause diarrhea.  It also makes it easier to divide doses so I can take it throughout the day.  I use a dropper and mix it into drinks.  The one I use is made by Good State.

 

Some people have said that they notice a revving of symptoms after starting magnesium supplementation.  Perhaps this is due to the involvement with ATP or maybe they coincidentally experienced a wave.  Carolyn Dean M.D., N.D.- the author of the book “The Magnesium Miracle” has a section in her book entitled “WHEN MAGNESIUM MAKES ME WORSE” where she discusses possible reasons why some people might feel worse after taking magnesium.  Her reasons as to why this may happen include: Not taking enough magnesium or taking too much, interactions with heart or thyroid medications, taking too much Vitamin D or calcium…to name a few. (26)

 

It is important to note that Dr. Dean also warns that people with any of the following conditions should avoid taking magnesium: kidney failure, myasthenia gravis, excessively slow hear rate, bowel obstruction. (26)

 

A word of caution for anyone thinking about using magnesium oils that are applied directly to the skin.  Applying magnesium oil to your skin may stimulate production of DHEA. (26)  This may potentially cause problems for people coming off benzos as DHEA acts a negative allosteric modulator (NAM) of the GABAAR (27), which means it reduces the effect of GABA.  It is also acts as a Positive Allosteric Modulator (PAM) of the NMDA receptor (NMDAR), which means it enhances the modulation of NMDARs.  Obviously, this would be the exact opposite effect one would desire while recovering from benzos.

 

 

 

1) Bacopa Monnieri

https://en.wikipedia.org/wiki/Bacopa_monnieri#Pharmacology

2) Acetylcholinesterase

https://en.wikipedia.org/wiki/Acetylcholinesterase

 

3) Sarin

https://en.wikipedia.org/wiki/Sarinhttps://en.wikipedia.org/wiki/Sarin

 

4) Choline acetyltransferase

https://en.wikipedia.org/wiki/Choline_acetyltransferase

 

5) Macrophages

https://en.wikipedia.org/wiki/Macrophage

 

6) Vitamin D, omega-3 may help clear amyloid plaques found in Alzheimer's

Rachel Champeau

UCLA Newsroom February 5, 2013

http://newsroom.ucla.edu/releases/vitamin-d-omega-3-may-help-clear-242465

 

7) Scientists pinpoint how vitamin D may help clear amyloid plaques found in Alzheimer's

Rachel Champeau

UCLA Newsroom March 6, 2012

http://newsroom.ucla.edu/releases/scientists-pinpoint-how-vitamin-229702

 

8] The redox chemistry of the Alzheimer's disease amyloid beta peptide.

Smith DG, Cappai R, Barnham KJ.

Biochim Biophys Acta. 2007 Aug;1768[8]:1976-90. Epub 2007 Feb 9.

http://www.sciencedirect.com/science/article/pii/S0005273607000387

 

9) Alterations to plasma melatonin and cortisol after evening alprazolam administration in humans.

McIntyre IM, Norman TR, Burrows GD, Armstrong SM.

Chronobiol Int. 1993 Jun;10(3):205-13. PMID:8319319

https://www.ncbi.nlm.nih.gov/pubmed/8319319

 

10) Suppression of plasma melatonin by a single dose of the benzodiazepine alprazolam in humans.

McIntyre IM, Burrows GD, Norman TR.

Biol Psychiatry. 1988 May;24(1):108-12. PMID:3370271

https://www.ncbi.nlm.nih.gov/pubmed/3370271

 

11) Stress and its influence on Alzheimer’s disease

UCIrvine Institute for Memory Impairments and Neurological Disorders (UCI MIND)- a National Institutes of Health (NIH) designated Alzheimer's Disease Research Center (ADRC)

http://www.mind.uci.edu/stress-and-its-influence-on-alzheimer%E2%80%99s-disease/

 

12) Modeling Alzheimer’s Disease

UCIrvine Institute for Memory Impairments and Neurological Disorders (UCI MIND)- a National Institutes of Health (NIH) designated Alzheimer's Disease Research Center (ADRC)

http://www.mind.uci.edu/research/cutting-edge-alzheimers-research/modeling-alzheimers-disease/

 

13) Vitamin K: The Missing Nutrient to Blame for Heart Attacks and Osteoporosis (Nope - NOT Calcium or Vitamin D)

Dr. Mercola

Health Articles, March 26, 2011

http://articles.mercola.com/sites/articles/archive/2011/03/26/the-delicate-dance-between-vitamins-d-and-k.aspx

 

14) Dr. Cannell on vitamin K2

John Cannell MD

Vitamin D Counsel November 27, 2013

http://www.vitamindcouncil.org/blog/dr-cannell-on-vitamin-k2/#

 

15) Organophosphate

https://en.wikipedia.org/wiki/Organophosphate

 

16) Acetylcholinesterase inhibitor

https://en.wikipedia.org/wiki/Acetylcholinesterase_inhibitor

 

17) Benzodiazepine use and risk of Alzheimer’s disease: case-control study

Billioti de Gage S, Moride Y, Ducruet T, Kurth T, Verdoux H, Tournier M, Pariente A, Bégaud B.

BMJ. 2014 Sep 9;349:g5205. doi: 10.1136/bmj.g5205.

PMID: 25208536

http://www.bmj.com/content/349/bmj.g5205

 

18) Efficient modulation of γ-aminobutyric acid type A receptors by piperine derivatives.

Schöffmann A, Wimmer L, Goldmann D, Khom S, Hintersteiner J, Baburin I, Schwarz T, Hintersteininger M, Pakfeifer P, Oufir M, Hamburger M, Erker T, Ecker GF, Mihovilovic MD, Hering S.

J Med Chem. 2014 Jul 10;57(13):5602-19. doi: 10.1021/jm5002277. Epub 2014 Jun 27. PMID:24905252

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106271/pdf/jm5002277.pdf

 

19) Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia.

Chung SY, Moriyama T, Uezu E, Uezu K, Hirata R, Yohena N, Masuda Y, Kokubu T, Yamamoto S.

J Nutr. 1995 Jun;125(6):1484-9. PMID:7782901

http://jn.nutrition.org/content/125/6/1484.full.pdf

 

20) A Pilot Cross-Over Study to Evaluate Human Oral Bioavailability of BCM-95CG (Biocurcumax), A Novel Bioenhanced Preparation of Curcumin.

Antony B, Merina B, Iyer VS, Judy N, Lennertz K, Joyal S.

Indian J Pharm Sci. 2008 Jul-Aug;70(4):445-9. doi: 10.4103/0250-474X.44591. PMID:20046768

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792534/

 

21) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease.

Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL.

Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922. PMID:21475195

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086762/

 

22) Curcumin The 21st Century Cure

Jan McBarron, M.D., N.D.

Too Your Health Books, 2012 ISBN: 978-0-9815818-9-7

 

23) Gastrointestinal and Cardiovascular Risk of Nonsteroidal Anti-inflammatory Drugs

Abdulwahed Al-Saeed

Oman Med J. 2011 November; 26(6): 385–391. doi: 10.5001/omj.2011.101

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251190/pdf/OMJ-D-10-00068.pdf

 

24) Microglia

https://en.wikipedia.org/wiki/Microglia

 

25) Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcumin.

Fiala M, Liu PT, Espinosa-Jeffrey A, Rosenthal MJ, Bernard G, Ringman JM, Sayre J, Zhang L, Zaghi J, Dejbakhsh S, Chiang B, Hui J, Mahanian M, Baghaee A, Hong P, Cashman J.

Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12849-54. Epub 2007 Jul 24. PMID:17652175

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1937555/pdf/zpq12849.pdf

 

26) The Magnesium Miracle

Carolyn Dean MD ND

Ballantine Books, NY 2014

ISBN: 978-0-345-49458-0

 

27) Dehydroepiandrosterone

Mechanism of Action

Wikipedia the free encyclopedia

https://en.wikipedia.org/wiki/Dehydroepiandrosterone

 

28) Characterization of ATP Alternations in an Alzheimer's Disease Transgenic Mouse Model.

Zhang C, Rissman RA, Feng J.

J Alzheimers Dis. 2014 Sep 26. [Epub ahead of print] PMID:25261448

http://www.ncbi.nlm.nih.gov/pubmed/25261448

 

Dear God,

 

Be careful out there, folks!

 

:)

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