Help keep your loved ones safe with the Home Safety Checklist.
RSS Feed Print
aromatherapy in the treatment of Alzheimer's disease
Lane Simonian
Posted: Wednesday, December 14, 2011 6:48 PM
Joined: 12/12/2011
Posts: 4436


I am assuming many people are going back and forth between the two boards, but I am going to try to summarize the support for aromatherapy here as well as some of the possible risk factors.  I received many thoughtful questions and responses on the old boards (including links to two of the three clinical trial on essential oils in the treatment of Alzheimer's disease).  If anyone is interested, they back to the old boards under the threads aromatherapy in the treatment of Alzheimer's disease and a unifying hypothesis for Alzheimer's disease.

First let me reiterate my hypothesis for Alzheimer's disease (which has taken me seven years and hundreds of hours of research).  Peroxynitrite-mediated damage is widespread in Alzheimer's disease.  Among the factors that lead to the formation of peroxynitrites are high glucose levels, high blood pressure due to high sodium levels, Down's syndrome, the APOE4 gene, presenilin gene mutations, bisphosphonate osteoporosis drugs (such as Fosamax), mercury, aluminum fluoride, late estrogen replacement therapy, and stress.  Peroxynitrties oxidize BH4 (a precursor to several neurotransmitters), glucose transport systems, choline transport systems, the enzyme choline acetyltransferase, g proteins coupled to receptors involved in short-term memory (muscarinic acetylcholine), mood (serotonin and opioid), sleep (serotonin and melatonin), behavior (adrenergic), alertness (dopamine), and smell (olfactory).  Peroxynitrites lower levels of free intracellular magnesium which results in the release of glutamate and the influx of calcium which are toxic to nerve cells.  They contribute to lipid peroxidation which damage cell membranes.  They contribute to the hyperphosphorylation and nitration of tau proteins which inhibit neurotransmission.

I am neither a fan nor highly adverse to animal studies.  The alzheimer's in mice and other animals is not the same as the alzheimer's in human beings, nor are mice physiologically the equivalent of human beings.  And yet, the differences are often not that great.  I won't cite the studies, but every single peroxynitrite scavenger (which also partially reverse oxidation and probably nitration) has ameliorated Alzheimer's disease in animal models.  These include a variety of polyphenols and methoxyphenols such as rosmarinic acid, cinnamon extract, grape seed extract, SuHeXiang Wan essential oil, and Zataria multiflora Boiss. essential oil.  By donating two hydrogen, these compounds convert peroxynitrties into water and a nitrogen dioxide anion (which appears to a fairly stable compound).  They also add hydrogen back to the receptors listed above so that there is some improvements in sleep, short-term memory, alertness, mood, and perhaps behavior (all the studies on the latter are mixed).

Now for the clinical trials (I apologize for not being competent to post the studies).  Jimbo and colleagues found significant improvements in cognitive function in  28 patients with dementia (including 17 with Alzheimer's disease) after receiving rosemary and lemon essential oil in the morning and lavender and orange in the evening through a diffuser for 28 days.  This study seems to indicate that peroxynitrites are at the root of other forms of dementia, although the tests seem to indicate the most improvement among Alzheimer's patients (this may be due to the fact that the system of smell is directly linked to the hippocampus--the area of the brain most damaged by Alzheimer's disease).  The cite for this clinical trial is Jimbo D, Kimura Y, Taniguchi M, Inoue M, Urakami  K. The effect of aromatherapy on patients with Alzheimer's disease.  Pyschogeriatrics 9; 4 (2009): 173-9,  The other two clinical trials by Akhondzadeh delivered essential oils via tinctures rather than aromatherapy, but the results are quite similar to Jimbo's trial (albeit using different tests for cognitive function).  In two separate trials lasting 16 weeks, approximately forty patients with Alzheimer's disease (it's hard to decipher how many patients completed the trial so 40 is just an estimate) showed significant improvements in cognitive function.  The cites for these studies are Akhondzadeh S, Noroozian M, Mohammadi M, Ohandina S, Jamshidi AH, et al. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised placebo-controlled trial. J Neurosurg Psychiatry 2003; 74:863-6 and Akhondzadeh S, Noroozian M, Mohammadi M, Ohandina S, Jamshidid AH, et al. Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized and placebo-controlled trial. J Clin Pharm Ther 2003 Feb; 28(1):53-9 The authors acknowledge their studies included a small number of participants, but the fact (or apparent fact) that approximately 70 people all showed significant improvements in cognitive abilities following treatment with essential oils should be a strong incentive for other researchers to pursue larger scale clinical trials.

In regards to case studies (yes, I know how much scientists hate case studies, but like animal studies they also have a place), I would recommend the Texas State Research on Aromatherapy, the study by East Carolina University--ECU scholars studies links between scents and memory, and the website of Potomac Homes (I also include my mother as a case study as we began to treat her with aromatherapy four years ago--starting with rosemary essential oil and since adding clove, cinnamon leaf, sage, oregano, thyme, peppermint, laurel, and orange.  She now recognizes her home again, feels comfortable around her brother--who she used to think was an impostor, sleeps through the night, can remember and often spell her name, can remember taking a walk, can recite the alphabet, can count to ten, and is much more alert and aware than before).

In terms of risk, I prefer aromatherapy over tinctures, because finding the proper dilution requires a lot of expertise.  Tinctures can be toxic-- to the liver for example.  Here are a list of some of the other risk factors for essential oil: coma (if breathed too long and too often), allergic reactions (headaches and vomiting predominantly), perhaps a slight risk of increased blood pressure, increased risk of seizure for people prone to seizures, increased risk of miscarriage, and possibly increased risk of cancer with very prolonged exposures.  Other than allergies, the risk factors for aromatherapy appear to be very minimal and very rare.

I would not say the evidence that aromatherapy in the treatment of Alzheimer's disease is weak.  I just don't think many people have looked closely at the evidence (although with substantial qualifications both the Canadian and British versions of the Alzheimer's Association have listed aromatherapy as a possible alternative treatment for Alzheimer's disease).  The interest in aromatherapy as a treatment for Alzheimer's disease is much greater in countries outside of the United States and that has limited the exposure of this alternative treatment in the United States.  I am always looking for more evidence--case studies, animal studies, clinical trials--to build on what has already been observed.



JAB
Posted: Thursday, December 15, 2011 1:05 PM
Joined: 11/30/2011
Posts: 740


Hey, Lane.  Thanks for starting the thread.

"The alzheimer's in mice and other animals is not the same as the alzheimer's in human beings, nor are mice physiologically the equivalent of human beings.  And yet, the differences are often not that great."

That may be true for many disorders, but not for Alzheimer's.  Mice do not naturally develop AD, they don't even naturally produce APP (the precursor to Abeta, which is the primary component in AD plaques.)  The only way mice can be used in studies on AD is if they are genetically engineered to mimic some small part of the AD cascade.  If I recall correctly, something like 200 different genes would have to be inserted into their genome to mimic everything that is known to be affected in humans, and of course, that isn't possible -- the mice never develop and grow.  There are dozens of different strains that are used to study select parts of AD ... hypothetically.

As for being able to treat Alzheimer's in genetically engineered mice ... I'm beginning to think there isn't anything that won't be found to be effective.  To date, not a single drug that was developed using mice has made it through clinical trials.  Researchers are beginning to doubt the utility of mice at all, for a number of different reasons.  And they refer to genetically-engineered mice as having "mouseheimer's" since whatever they "have" is so different from AD.

Which is why I warned you that I'm not fond of animal models when it comes to studying Alzheimer's.


 


JAB
Posted: Thursday, December 15, 2011 2:55 PM
Joined: 11/30/2011
Posts: 740


For those who are interested in reading the papers themselves (those Lane mentions and those cited by other members on one of his threads):

Jimbo et al, Psychogeriatrics 2009
http://onlinelibrary.wiley.com/doi/10.1111/j.1479-8301.2009.00299.x/full
This studied lemon and rosemary essential oil in the morning plus lavender and orange essential oils in the evening.  It was a very small (28 people, only 17 of whom had Alzheimer's), very short (28 days of the treatment) study.  It was also open label, and the results of open-label studies are always suspect.  Neither the GBSS-J nor the TDAS is widely used to determine the level of cognitive function in the U.S. -- I'm not familiar with them, so I cannot comment on how thoroughly they have been validated.

Akhondzadeh et al, J Neruol Neureosurg Psychiatry 2003
http://jnnp.bmj.com/content/74/7/863.abstract
This studied Melissa officinalis ("lemon balm") leaf extract.  This one had a double-blind, randomized, placebo-controlled design, lasted 4 months and used standard tests (ADAS-cog and CDR-SB).  However, it is still much too underpowered (only 35 patients, 20 in the treated group and 15 placebo) for the results to be reliable.  And it appears that the decline in the control group was unusually steep.

Akhondzadeh et al, J Neruol Neureosurg Psychiatry 2003
http://lamiaceaedirectory.8m.com/Article75.pdf
This is another study by the same lab as above, on Salvia officinalis (garden sage).  It had the same basic design, but with only 30 patients completing the study, 15 in each cohort.  Authors note that weaknesses include the small number of patients and short period of follow-up.

Moss et al, Int J Neurosci 2008
http://www.ncbi.nlm.nih.gov/pubmed/18041606
This was a somewhat larger study (144 participants), none of whom had dementia, randomly assigned to ylang-ylang, peppermint, or placebo.  Ylang-ylang was reported to impair memory and lengthen processing speed.  Peppermint purportedly enhanced memory.

Moss et al, Int J Neurosci 2003
http://informahealthcare.com/doi/abs/10.1080/00207450390161903
Like the above Moss et al study, this also involved 144 healthy adults, randomly assigned to lavender or rosemary essential oils, or placebo.  Lavender significantly decreased working memory, and impaired reaction times for both memory and attention, in comparison to controls. Rosemary enhanced overall quality of memory and secondary memory, but also impaired speed of memory compared to controls.

Onward also provided a link to The Tangled Neuron website, which notes that results with lavender have been "mixed", citing a MedlinePlus (National Institutes of Health) analysis:
http://www.nlm.nih.gov/medlineplus/druginfo/natural/838.html

Sorry, Lane, but I'd still have to say that the evidence is very weak. Only a single, small study on any given treatment in dementia patients, with the exception of lavender. Certainly, I'd welcome more studies in the area -- I find the concept interesting, which is why I'd been looking into it.  However, I'd like to see a lot more emphasis on safety.  The Akhondzadeh team hypothesizes that lemon balm and garden sage may work by affecting the cholinergic neurotransmission system.  Anything that affects neurotransmission in the brain needs to be treated with care.

By the way, posting links is easy.  Just copy the URL in the box at the very top of your browser when you're at the website of the paper, and paste into your post.
Lane Simonian
Posted: Thursday, December 15, 2011 11:00 PM
Joined: 12/12/2011
Posts: 4436


Yes, the amyloid plaque in mice is manufactured or engineered.  Here is the larger point, however.  Peroxynitrites cause dementia in a great variety of animals, including human beings because they lower the production of acetylcholine. Amyloid plaques contribute to the production of peroxynitrites by entombing zinc and copper (the Alzheimer's process begins even before the widespread formation of amyloid plaques because phospholipase C is involved in the export of zinc).  The enzyme (superoxide dismutase) which converts superoxide into hydrogen peroxide depends on zinc and copper.  This enzyme, thus, does not  work properly in people with Alzheimer's disease.  This malfunction contributes to high levels of peroxynitrites (superoxides combine with inducible nitric oxide to form peroxynitrites).  Moreover, free intracellular zinc is needed to keep homocysteine levels low.  Phospholipase C and homocysteine via protein kinase C activates tumor necrosis factor alpha which in turn activates nadph oxidase (forming superoxide anions) and nuclear factor kappa b (forming inducible nitric oxide).  This, too, leads to high levels of peroxynitrites.  Peroxynitrites oxidize a variety of g proteins, enzymes, and transport systems and nitrite tau proteins.  This happens with high levels of phospholipase C activity and the subsequent formation of amyloid plaques whether you are a mouse or a human being.  Thus, while some of the inferences drawn from mouse studies may be misleading that regarding peroxynitrites are not.  That is why peroxynitrite scavengers have not only worked in mouse models of Alzheimer's disease but also in clinical trials with human beings.
amelia99
Posted: Thursday, December 15, 2011 11:02 PM
Joined: 12/1/2011
Posts: 6


I just read an article about the sense of smell being one of the first things to go in AD. They were discussing that maybe the treatment of aromatherapy may help with AD by using it early in first stage. I can't find the article right now, but I'll look for it and post it. It was interesting and caught my eye, since I've been reading Lane's postings concerning aromatherapy.

I've been thinking about this and it does make sense that smelling something affects the brain. You inhale it and it enters your system such as when you inhale anesthesia and we all know how that affects us and our LO. Drug addicts who sniff glue and paint fumes and other chemicals. These are obvious chemicals but then most things we smell do have a chemical make up.

There are some smells that literally make people sick to their stomachs and will cause them to have nausea and vomit or give them a headache. (Pregnant women are a good example of the nausea and vomiting).Cutting onions makes us cry. Inhaling steam unclogs the nasal passages and sniffing Vick's helps too.

The smell of food cooking will stimulate the saliva and will start the process of the stomach and digestive system to ready itself for food. Some smells will make us feel good such as freshly cut grass, fabric softener etc. Some smells will bring back memories, like hot chocolate, cotton candy, the ocean etc We all have smells that bring back memories from our youth or some occasion.

It seems as if almost everything we ingest, smell or inhale, RX drugs, supplements etc.some part of it finds it way to our brain. The sense of smell has a good amount of reaction on our body and brain, so it seems entirely reasonable that aromatherapy may have an affect on AD brains.


amelia99
Posted: Thursday, December 15, 2011 11:31 PM
Joined: 12/1/2011
Posts: 6


While looking for that article, which I still haven't found, I ran across this one that cites a mouse study done by researchers who have developed a drug that reversed the damage to the olfactory bulb by AB plaques and returned the sense of smell within 2 weeks.

 

http://case.edu/medicus/breakingnews/wessonad.html 


Lane Simonian
Posted: Thursday, December 15, 2011 11:34 PM
Joined: 12/12/2011
Posts: 4436


I, too, would welcome further studies on aromatherapy in the treatment of Alzheimer's disease (thank you for the posting advice, so that hopefully I can post future studies) .  I have been begging for further studies for four years, but I either receive no response, a passive aggressive response, or a negative response.  Those few researchers who recognize the potential of phenolic compounds in the treatment of Alzheimer's disease want to produce synthetic versions to patent them.  The problem, I suppose, is that the natural compounds (methoxyphenols, for instance) appear not to need alteration to be effective.

 

I was grateful for the additional posts on studies with essential oils in healthy adults.  It has led me to replace the use of Ylang Ylang with Peppermint essential oil.  Having said that, though, there is no clinical proof the oils have the same effect on Alzheimer's patients as they have on non-Alzheimer's patients.  I will therefore focus on the studies using essential oils in patients with dementia.

 

I am not in a position to evaluate whether one test for Alzheimer's is any more reliable than another test nor can I judge the credentials of the researchers nor whether their clinical trials were properly designed.  It is true that Jimbo and colleagues did not use a placebo and I don't completely understand their methodology for factoring out caregivers' perspectives.  However, I would be surprised if they would state that "all patients showed significant improvement in personal orientation related to cognitive function" if they were not confident in their methodology.  The trial was a very short one and in my own personal experience (using one essential oil and inhalation from a bottle rather than four essential oils and a diffuser) it does take about a month to observe any notable difference.  It is unfortunate that not more people were enrolled in the trial and a longer time frame was not used (at least four months), but hopefully Jimbo and colleagues are working on a more extensive trial.

 

The rapid decline in the placebo group in the Akhondzadeh study has been noted by other researchers.  Some researchers think the improvement in the group receiving the essential oils was too great.  They also wanted a description of the placebo used in both studies.  Akhondzadeh's trial was of  longer length than Jimbo's study and used what apparently are the more standard tests for cognitive function in Alzheimer's patients.

 

Again, here is my larger point: a person can say they don't accept animal studies, they can say they don't like case studies, they can point to flaws in methodology (all valid points), but they cannot say that essential oils have not shown effectiveness in various studies.  Furthermore, once you understand the role of peroxynitrties in Alzheimer's disease and the role of several chemicals in various essential oils in not only neutralizing this toxin, but also in partially reversing its effects, then the results from the animal studies, case studies, and clinical trials make a great deal of sense.  So, we can disagree about whether the evidence is weak or strong, but based on what we already now the need for more studies is urgent.


Lane Simonian
Posted: Thursday, December 15, 2011 11:55 PM
Joined: 12/12/2011
Posts: 4436


These are all great insights Amelia.  The system of smell is connected to critical parts of the brain involved in memory, recognition, and emotion.  Thank you also for the post.  What I liked about this study is that it demonstrates that the damage done to smell (and I would think by extension to short-term memory) occurs even before much amyloid plaque has formed.  Stop the formation of the plaque and you stop the onset of Alzheimer's disease, but perhaps much of the damage has already been done to the brain once the plaques form in significant amounts (amyloid plaques contribute to the formation of peroxynitrites, but peroxynitrtites from before the large-scale appearance of the plaques).  Thus the notion that amyloid plaques are the cause of Alzheimer's disease is both paradoxically true and false (perhaps better put they are part of the process of Alzheimer's disease).  If you look at all the g proteins oxidized by peroxynitrites, they are all reflected in the symptoms of Alzheimer's disease: smell (olfactory), short-term memory (muscarinic acetylcholine), social recognition (oxytocin), mood (serotonin and opioid), sleep (melatonin and serotonin), and alertness (dopamine).  You reverse the damage to one, you reverse the damage to all.  And it has already been shown that the damage to the olfactory receptors can be reversed.  Smell and memory are linked in so many ways, including that the compounds involved in both pass through the same type of receptor (g protein-coupled receptor).  Smell is not just a sense, it involves chemicals that can either help or hurt the brain.
Lane Simonian
Posted: Friday, December 16, 2011 10:12 AM
Joined: 12/12/2011
Posts: 4436


To repeat the essential point, peroxynitrites are held to be the main cause of short-term memory impairment in Alzheimer's disease.  Weak peroxynitrite scavengers may delay the progression of the disease, but not stop its course (this includes dimethyl compounds such as dimebon and memantine).  Strong peroxynitrite scavengers probably not only stop the progression of the disease, but also reverse it (although at this point not cure it).  This group of peroxynitrite scavengers include polyphenols (such as rosmarinic acid that contain multiple OH groups), methoxyphenols (eugenol, carvacrol, and thymol), minocylcine and other tetracycline antibiotics, and ketone boides (I apologize for confusing ketones with ketone bodies, ketones contain a methyl group but ketone boides often contain more that one OH group as do tetracycline antibiotics).  The strong peroxynitrite scavengers are able to donate at least two hydrogen atoms and electrons converting peroxynitrites to water and a nitrogen dioxide anion.  They are also able to add hydrogen back to g proteins coupled to receptors involved in smell, short-term memory, sleep, mood, social recognition, and alertness.  There are thus multiple ways to treat this disease, including the use of aromatherapy with essential oils high in methoxyphenols.  Here are the links for rosmarinic acid and eugenol.http://www.ncbi.nlm.nih.gov/pubmed/17420060

http://www.ingentaconnect.com/content/ben/cbc/

2006/00000002/00000001/art00005
 

JAB
Posted: Friday, December 16, 2011 1:01 PM
Joined: 11/30/2011
Posts: 740


Lane, you've made a number of statements about what happens in human beings, e.g.:

"Peroxynitrites cause dementia in a great variety of animals, including human beings because they lower the production of acetylcholine."

"This happens with high levels of phospholipase C activity and the subsequent formation of amyloid plaques whether you are a mouse or a human being."

"That is why peroxynitrite scavengers have not only worked in mouse models of Alzheimer's disease but also in clinical trials with human beings."

Please provide references to studies done in human beings that support these statements.  (Links, please -- many of our members don't know how to search the literature, so citations don't help them locate the papers to read for themselves what you're talking about.  And a link to the full paper is best, not just an abstract in PubMed, because abstracts can be wildly misleading.  I'm delighted to see you've learned how to post links. )


I realize you've put a lot of time and effort into researching your hypothesis.  However, it appears at first blush (and I readily admit I haven't read most of your posts, so if I'm wrong, please forgive me) that you haven't considered certain aspects of it.  For example, for an antioxidant compound to counteract any negative effects of peroxynitrites, that compound has to make it to the intracellular site where the peroxynitrite is doing damage, and to make it there in sufficiently high concentrations to scavenge the peroxynitrite free radicals before the damage is done.  Plenty of researchers are looking into free radical scavengers as potential treatments for, or protection against, Alzheimer's.  So far, even though the pre-clinical data has been very promising, the clinical trial results have been underwhelming.  Many researchers (most, as far as I know) believe that's because no single compound is going to make it through the body to the target cells and be taken up in high enough levels in all of the diverse types of target cells and into their diverse intracellular organelles to be affective.  Focus has therefore shifted from treatment with a single type of antioxidant to treatments involving multiple compounds, each one carefully selected to target certain key structures within key types of brain cells.

Take smell, for example.  The odorant is not taken up by the human body and does not enter the brain to trigger a "smell" response.  Instead, the odorant binds reversibly to biomacromolecules, called olfactory receptors, on the cilia on the outer surface of olfactory sensory neuron cells in the nose.  The binding interaction triggers a chemical response cascade.  
http://en.wikipedia.org/wiki/Olfactory_receptor
http://openwetware.org/wiki/BIO254:ORs


I would also note that the sense of smell per se is not necessarily lost in the earlier stages of Alzheimer's in some patients.  Instead, it appears to be the ability to identify certain odorants at more dilute concentrations that is lost.  I.e., it is more of an agnosia phenomenon than a malfunction of the nose.

In fact, very little of what we ingest or inhale makes it into brain cells.  For example, the human body may not absorb what is ingested, may not digest it, and/or may quickly metabolize it and/or excrete it.  And even most compounds that do enter the bloodstream intact cannot cross the blood-brain barrier.


The larger point is not whether one "accepts" a given study or type of study, but whether one understands their limitations when it comes to extrapolating to what might be going on in the living human brain of a dementia patient.


There are other problems with Akhondzadeh study data that would bother an experienced researcher.  For example, the data is far too tightly clustered (the standard deviations are much too small) at each data point for such a tiny study involving dementia patients.  Something about the studies simply wasn't done correctly, i.e., there are factors other than the essential oils affecting the outcome.

It's not surprising that other critics have focused on the placebo that was used -- the data are much more what one would expect from an open-label study than a double-blind study.  And it is difficult to imagine how one would design a suitable placebo for an aromatherapy study to be truly "blind".  A pill that contains placebo, for example, will be exactly the same in appearance (color, size, shape, hardness, etc), smell, and taste as a pill that contains the drug.


And yes, the experts at NIH not only can, but do, say that essential oils have not been shown to be effective.  You have to understand clinical trials, experimental design, data analysis, etc etc etc before you can claim that the studies done to date on any treatment produced definitive proof.

For example, the results of small studies on dementia patients can produce wildly skewed data, no matter how much care was taken in designing and executing the test protocols.  Not one knowledgeable researcher will accept the apparent findings from a single large study, let alone a small one.  

I'll give you an example.  There was a fairly large (183 participants), well-designed and -executed Phase II clinical trial on dimebon that produced wildly exciting results.  The data appeared to indicate dimebon is actually disease-altering.  Several additional, much larger, Phase III trials were launched, to much fanfare.  The results from the first Phase III trial to be completed (involving 600 patients) were stunning:  there was absolutely no difference between dimebon and placebo.  For an interesting early analysis, see:
http://www.ft.com/cms/s/2/089f09b2-264a-11df-aff3-

  00144feabdc0.html#axzz1giwJL7uz

Note in particular the comment, "... the medical community regularly sees smaller trials that originally show stellar results and fail in larger definitive trials."  And the "smaller" trial here had, what, six times as many test subjects as one of the Akhondzadeh studies.

The FDA requires at least two large, Phase III clinical trials that duplicate results before they'll consider approving a treatment.  And the data have to be of very high caliber before two Phase IIIs are considered adequate.


(And one little aside about plaque:  many researchers believe the formation of plaque is actually a protective mechanism, and that one or more of the soluble forms of Abeta are likely to be the toxic species.)

 


JAB
Posted: Friday, December 16, 2011 2:03 PM
Joined: 11/30/2011
Posts: 740


The rosmarinic acid study is mildly interesting (sorry, mice don't do much for me ) but it's hard to see how it supports aromatherapy as a treatment for Alzheimer's.  

For one thing, the memory impairment was created by injecting Abeta(25-35) directly into the mouse brains.  ("i.c.v." is "intracerebroventricular")  This doesn't begin to mimic what happens in the diseased human brain.  

Moreover, the rosmarinic acid was administered by intraperitoneal inject, not by inhalation.  That's going to have a major impact on distribution and metabolism.  (One also wonders how volatile rosmarinic acid is -- it may not be possible to get a reasonable dose into the body by inhalation, even if its fate were to be the same as by injection.)

Finally, the study was aimed at evaluating the potential for using rosmarinic acid to prevent the development of memory problems, not to treat Alzheimer's once it's already present.


The possible mechanism of action of eugenol discussed in the Irie paper is the inhibition of Abeta-induced excessive calcium influx and thereby attenuation of excitotoxicity (i.e., behaving in a manner somewhat similar to Namenda).  You may find this paper to be of interest, since it discusses much of the information that is known about eugenol:

http://www.asianjtm.com/qikan/manage/wenzhang/AJTM2009-4(4)-1.pdf

Note this part of the discussion:

"However, according to our
findings, the action of clove extract on cognition is
inversely dependent on its concentration. The negative
relationship involving the dose-dependant activity of
clove extract may be due to its hypnotic and anesthetic
effect or to its vasodilator, hypotensive and
bradycardial activity which may produce some
degree of motor dysfunction."

The most important constituent of clove is eugenol.


Lane Simonian
Posted: Friday, December 16, 2011 4:33 PM
Joined: 12/12/2011
Posts: 4436


It is an open question whether the chemicals in a smell can enter the brain even if the g protein coupled to the receptor is damaged.  The argument for aromatherapy is the following: the chemicals in methoxyphenols partially reverse the damage done to g proteins coupled to olfactory receptors by peroxynitrites and then enter the hippocampus where they then partially reverse the oxidative damage done by peroxynitrites to another g protein coupled to a receptor involved in short-term memory (muscarinic acetylcholine).  The methoxyphenols in several essential oils are highly concentrated and have a direct route to the hippocampus and for that reason I believe that they have a distinct advantage over other antioxidants.  This is probably part of the problem with other phenolic compounds in mouse studies--they enter in large enough concentrations in mouse brains to make a difference, but not in great enough concentrations in human brains to make a difference.  The study on rosmarinic acid was given just to indicate that some researchers believe that peroxynitrites are the cause of short-term memory impairment in Alzheimer's disease.  Here are more direct mouse studies involving essential oils (and one on Ocimum sanctum since the very good article you posted makes reference to it). http://www.ncbi.nlm.nih.gov/pubmed/22070531

 http://www.ncbi.nlm.nih.gov/pubmed/21905282 

http://www.greenpharmacy.info/article.asp?issn=0973-8258;

year=2009;volume=3;issue=1;spage=6;epage=15;aulast=Raghavendra 

The first article notes that acute toxicity levels in Zataria multiflora Boiss. essential oil occur at much higher doses than the therapeutic dose in mice at least (the study does caution that more studies are necessary to confirm this as well as the potential effectiveness of Zataria multiflora Boiss. essential oil in Alzheimer's disease.  This essential oil mainly contains carvacrol and thymol),  At very high levels methoxyphenols such as carvacrol, thymol, and eugenol can become pro-oxidants rather than antioxidants, but it appears to be at very high levels.  I wouldn't be sniffing from the bottle for minutes at a time or have the diffusers running for hours at a time without proper dilution  (and you don't have to do either for the essential oils to be effective).

 

The point you make on eugenol and Namenda (memantine) is right on target. They both inhibit calcium influx and the release of glutamate.  Eugenol, however is a better peroxynitrite scavenger than Namenda and therefore it is better able to limit the influx of calcium and the release of glutamate; which means that it is better at protecting neurons from cell death (peroxynitrites cause both problems by lowering levels of intracellular magnesium). http://www.ncbi.nlm.nih.gov/pubmed/1935602  As far as the Akhondzadeh's studies go, I see plenty of head scratching over them.  People insist something else had to be at work, but my question is what.  Maybe the essential oils were just that effective.

 

Many clinical trials on Alzheimer's disease have failed (and yet some of the drugs continue to be used).  They have either dealt with a passing phase of the disease (high cholinesterase activity).  The compounds cannot be delivered in high enough doses to be effective.  The peroxynitrite scavengers employed are weak ones (Namenda and dimebon).  The drugs don't effectively cross the blood-brain barrier.  The problem being targeted is only a part of the problem of the overall disease (efforts to dissolve amyloid plaques).  And on and on and on.  There are reasons why all the trials have failed so far--they failed because the people conducting them did not understand the cause of the disease (sure amyloid plaques, hyperphosphorylated tau proteins, glutamate release, and calcium influx seem to be involved in some way, but how and why).  Once you understand the disease, the likelihood of the trial succeeding increases substantially.  Aromatherapy/essential oils have succeeded in treating Alzheimer's disease in mouse models, case studies, and small-scale clinical trials and if anyone has the money and courage to do it--they are very likely to work in large-scale clinical trials because they treat the cause of the disease--peroxynitrites.


Lane Simonian
Posted: Friday, December 16, 2011 4:45 PM
Joined: 12/12/2011
Posts: 4436


The one link failed so let me give a quick reference: Li et al. Peroxynitrite induces apotosis and decline in intracellular free magnesim with concomitant elevation in  [Ca2+] in rat aortic smooth muscle cells:  possible roles of extracellular and intracellular magnesium ions in peroxynitrite-induced cell death.
Lane Simonian
Posted: Friday, December 16, 2011 5:06 PM
Joined: 12/12/2011
Posts: 4436


I apologize for not seeing the top part of your comment.  Yes, it pleases me that I can now make links most of the time.  I will try to find the full articles whenever possible.  Here are two more links indicating the potential effectiveness of peroxynitrite scavengers in Alzheimer's disease  http://www.nature.com/npp/journal/v32/n11/full/1301377a.html

http://www.jbc.org/content/early/2010/11/16/jbc.M110.169565l.  The following abstract does not mention Alzheimer's disease specifically.  http://www.ncbi.nlm.nih.gov/pubmed/15941312 but is another example of an essential oil as a peroxynitrite scavenger.  To briefly answer a previous question, "dummy" smells are sometimes used in trials with essential oils as a placebo--this is about the best that one can do.  I have about exhausted my studies but as I find more I will post them.



Lane Simonian
Posted: Friday, December 16, 2011 5:13 PM
Joined: 12/12/2011
Posts: 4436


O,k. here is the title from the nature.com link: Minocycline attenuates neuronal cell death and improves cognitive impairment in Alzheimer's disease models Neuropsychopharmacology 2007 Nov; 32(11): 2393-404.  I will get these links down eventually
JAB
Posted: Friday, December 16, 2011 6:37 PM
Joined: 11/30/2011
Posts: 740


http://www.nature.com/npp/journal/v32/n11/full/1301377a.html 

 

It looks like there's a break in your link after "nature.com" that is making it redirect to the journal home page.  Try posting your links in a separate line, rather than as part of a paragraph, and see if that helps.


JAB
Posted: Friday, December 16, 2011 7:02 PM
Joined: 11/30/2011
Posts: 740


I am very confused by your statements regarding the radical scavenging properties of Namenda as having anything to do with its efficacy in treating Alzheimer's.  One of our members asked me for an explanation, which I posted:



http://alzheimers.infopop.cc/eve/forums/a/tpc/f/214102241/

m/400307674? r=796300874#796300874 

 

There was never any mention of scavenging in any of the papers I read.

 

Could you please provide references that discuss the radical scavenging properties of Namenda as they affect its biological activity?


JAB
Posted: Friday, December 16, 2011 7:51 PM
Joined: 11/30/2011
Posts: 740


I'm also quite confused by your statements regarding G-protein coupled receptors (GPCRs) and entry of odorant molecules into the brain:

"It is an open question whether the chemicals in a smell can enter the brain even if the g protein coupled to the receptor is damaged.  The argument for aromatherapy is the following: the chemicals in methoxyphenols partially reverse the damage done to g proteins coupled to olfactory receptors by peroxynitrites and then enter the hippocampus where they then partially reverse the oxidative damage done by peroxynitrites to another g protein coupled to a receptor involved in short-term memory (muscarinic acetylcholine)."

GPCRs comprise a very large family of transmembrane biomolecules that are found in many different places in and on many different cell types.  Their biological function depends on the structure of the specific GPCR and the membrane to which it is bound.

http://en.wikipedia.org/wiki/G_protein-coupled_receptor

The GPCRs that are involved in the sense of smell are located in the outer surface of the olfactory epithelium (i.e., the outer layer of the skin on the roof of the nasal cavity).

http://en.wikipedia.org/wiki/Olfactory_epithelium

These GPCRs are not located in the brain, nor do they transport anything into the brain.  For that matter, they don't transport anything into the epithelial neuron cells in whose membranes they are bound.  The signal that is created when an odorant binds is a conformational change (i.e., a change in shape) in the GPCR.  When the GPCR has undergone this change in shape, it can then activate an associated G-protein by exchanging its bound GDP for a GTP.  That triggers a cascade of reactions within the epithelial neuron.
The odorant molecule, meanwhile, simply comes back off the GPCR into the air.  It does not enter the epithelial neuron cell.  And it certainly isn't transported from the outer layer of skin of the nasal cavity into the brain.

You do understand that a free radical scavenger acts by interacting with the oxidant (e.g., the peroxynitrite) to "deactivate" the oxidant.  It does not act by interacting with and repairing the damage done to a biomolecule by the peroxynitrite, yes?

http://physrev.physiology.org/content/87/1/315.full



Lane Simonian
Posted: Friday, December 16, 2011 10:14 PM
Joined: 12/12/2011
Posts: 4436


Let's start with the Namenda question first.  The NMDA rececptor is gated by magnesium.  If you lose most of the free intracellular magnesium, you increase the influx of calcium and the release of glutamate, which is probably the chief mechanism by which peroxynitrites contribute to the death of neurons. Compounds containing methyl groups such as dimebon and namenda appear to be (weak) peroxynitrite scavengers, although this is based on the peroxynitrite scavenging capabilities of other compounds containing methyl groups such as the following http://www.liebertonline.com/doi/abs/10.1089/jmf.2007.040.

 

The other questions that you raise are critical ones: do aromatic compounds enter the brain and can they reverse the damage done by peroxynitrites.  Here is one study indicating that aromatic compounds do enter the brain (in mice at least)  http://www.ncbi.nlm.nih.gov/pubmed/21639684 The notion that these compounds somehow get stuck in the nose flies in the face of all the positive and negative effects of aromatic compounds on human health (why is sniffing glue and breathing hydrocarbons harmful to the brains of human beings, for instance).  Indeed aromatic compounds are the most likely compounds to enter the brain.

 

The idea that peroxnitrite scavengers can only scavenge peroxynitrites and not reverse part of their damage is also incorrect.  G proteins are composed of sulfhydryl groups.  Peroxynitrites remove hydrogen from them so that they cease to function properly.  Some antioxidants act as hydrogen donors partailly restoring the function of g protein-coupled receptors.  Here is one example of an antioxidant restoring the function of a g protein coupled receptor  http://www.ncbi.nlm.nih.gov/pubmed/17191082 

 

So to summarize, the compounds in essential oils do reach other parts of the brain and they can help restore the function of g proteins coupled to critical receptors.

 

I have a question from a previous post: the NIH says that aromatherapy is not effective in the treatment of Alzheimer's disease.  On what basis does the NIH make that claim.  I don't mind people saying that aromatherapy is ineffective in the treatment of Alzheimer's disease, but they need to present the same level of evidence against its use as the level of evidence presented by people who support its use. http://ezinearticles.com/?Debunking-the-Debunkers---

The-True-Medicinal-Value-of-Aromatherapy&id=2584349 


Lane Simonian
Posted: Saturday, December 17, 2011 10:54 PM
Joined: 12/12/2011
Posts: 4436


I have a few quibbles with the following article (for example, I would say that essential oils can partially reverse the oxidation of  g proteins linked to receptors rather than clean receptor sites).  However, I think that the author clearly explains why essential oils are so effective at reaching different parts of the brain and how they could be an effective in the treatment of a variety of neurodegenerative diseases.http://www.rnoel.50megs.com/pdf/theblood.htm
SnowyLynne
Posted: Tuesday, December 20, 2011 10:42 AM
Joined: 12/1/2011
Posts: 29


I refused trials,I wanted the real medication,not phony balony...After 14 years I'm still doing great.Can't knock it....
Ttom
Posted: Tuesday, December 20, 2011 11:13 AM
Joined: 11/29/2011
Posts: 182


My wife wounldn't allow me to particapate in any trials. She wanted me to continue taking the Aricept and Namenda.
SnowyLynne
Posted: Tuesday, December 20, 2011 11:40 AM
Joined: 12/1/2011
Posts: 29


Good for her....She did the right thing....
JAB
Posted: Wednesday, December 21, 2011 4:24 PM
Joined: 11/30/2011
Posts: 740


"Compounds containing methyl groups such as dimebon and namenda appear to be (weak) peroxynitrite scavengers, although this is based on the peroxynitrite scavenging capabilities of other compounds containing methyl groups..."   

In all the papers I've read on these two drugs, I have never seen the slightest indication that their biological activity is, or even might be, due to their being peroxynitrite scavengers. 

Read the link I provided to my post on the biological activity of Namenda for current thought on its underlying mechanisms of function.

The current understanding of the biological activity of Namenda is based on a wide range of experiments, not on supposition.



JAB
Posted: Wednesday, December 21, 2011 4:57 PM
Joined: 11/30/2011
Posts: 740


"Here is one study indicating that aromatic compounds do enter the brain (in mice at least)  http://www.ncbi.nlm.nih.gov/pubmed/21639684 "

Lane, obviously you didn't even read the abstract carefully, let alone the entire paper.  The lemon balm was administered "i.p.", that is, intraperitoneal (injection into the abdominal cavity).

Please take a very close look at those two links I found for you which explain how the sense of smell works.


JAB
Posted: Wednesday, December 21, 2011 5:25 PM
Joined: 11/30/2011
Posts: 740


"Here is one example of an antioxidant restoring the function of a g protein coupled receptor"  http://www.ncbi.nlm.nih.gov/pubmed/17191082

The abstract (I bet you haven't read the full paper) says that D1R signaling in the kidneys is "restored" but does not say how it is restored.  It does not say -- as you imply -- that the oxidative damage done to a given GPCR was reversed by a direct chemical interaction between the oxidized site on the protein and a peroxinitrite scavenger.  Nor were the studies designed to be able to determine the mechanism whereby signaling was restored.  Instead, the studies were designed to help determine whether D1r oxidation contributes to D1R dysfunction in obese animals.



JAB
Posted: Wednesday, December 21, 2011 5:36 PM
Joined: 11/30/2011
Posts: 740


"I have a question from a previous post: the NIH says that aromatherapy is not effective in the treatment of Alzheimer's disease.  On what basis does the NIH make that claim."

That is not what I said.  I said, "And yes, the experts at NIH not only can, but do, say that essential oils have not been shown to be effective."

There is a huge difference between saying that essential oils have not been shown to be effective, and saying that aromatherapy is not effective.

For example, I provided you with a link to the Tangled Neuron website that other members had already given to you on the old forum, which cites an NIH analysis of lavender.  It said, among other things, that there is "insufficient evidence to rate effectiveness for agitation in dementia.  Study results have not agreed. In one study, nightly use of lavender oil in a bedside diffuser for 3 weeks reduced agitation in patients with various types of dementia. However, in another study, continuous use of lavender oil on a pad attached to a patient's shirt had no effect in a small group of patients with advanced dementia."

I.e., they're saying exactly what I've been saying:  the evidence for using essential oils in general, and aromatherapy in particular, is very weak.

 

 

"I don't mind people saying that aromatherapy is ineffective in the treatment of Alzheimer's disease, but they need to present the same level of evidence against its use as the level of evidence presented by people who support its use. http://ezinearticles.com/?Debunking-the-Debunkers---The-True-Medicinal-Value-of-Aromatherapy&id=2584349  "

 This article does not provide one single citation of a study in a peer-reviewed journal in support of its contentions.  This is hardly compelling evidence.


JAB
Posted: Wednesday, December 21, 2011 5:43 PM
Joined: 11/30/2011
Posts: 740


Now.  Let's get back to my earlier post, in which I asked you for references that support some rather sweeping statements that you made:

"Peroxynitrites cause dementia in a great variety of animals, including human beings because they lower the production of acetylcholine."

To my knowledge, they haven't even been shown to be risk factors for Alzheimer's, let alone established to cause it.

And

"That is why peroxynitrite scavengers have not only worked in mouse models of Alzheimer's disease but also in clinical trials with human beings."

Which peroxynitrite scavengers have "worked" in clinical trials with human beings?
JAB
Posted: Wednesday, December 21, 2011 8:03 PM
Joined: 11/30/2011
Posts: 740


As for the blog on the blood-brain barrier ... Lane, there is a great deal of misinformation and outright disinformation on the web, especially when it comes to unconventional "treatments" such as aromatherapy and some of the nutritional supplements that are touted for various disorders.  Vendors who sell such products are not incentivized to give you a balanced and objective analysis of the supportive evidence (even if they had researched and understood it).  You simply cannot trust anything that (a) you don't find at a reputable website and (b) that does not cite references to support what has been said.

You have no idea who the purported author of this blog might be, or even what he got his PhD in (English lit?  Archeology?  Medieval history?) -- if he did -- or what the "RA" stands for.  (Regulatory Affairs?  Radiology Assistant?  Royal Arch?  Regional Accreditation?) 

The properties of the blood-brain barrier have to be considered when developing drugs that have to reach cells within the brain.  For a much better explanation of the blood brain barrier, and what crosses it and when and how, see, e.g:

http://clincancerres.aacrjournals.org/content/13/6/1663.full

http://www.sciencedaily.com/releases/2011/04/110405124546.htm

http://www.sciencedaily.com/releases/2008/10/081022073724.htm

One thing which that blog fails to mention is that the BBB produces very high levels of proteins whose specific function is to pump foreign molecules right back out of any endothelial cells they might penetrate, while allowing other molecules (such as glucose and insulin) that are necessary to the functioning of the brain cells to cross the barrier.






Lane Simonian
Posted: Thursday, December 22, 2011 1:25 AM
Joined: 12/12/2011
Posts: 4436


You raise many issues, and I will try to respond to them.  Dimethyl groups containing two CH3 (such as dimebon and namenda) appear to be effective scavengers of peroxynitrites ( ONOO-) because they contribute two hydrogen atoms and two electrons converting them into water and a nitrogen dioxide anion.  This is not the traditional explanation for the action of these drugs, but the fact that methoxyphenols containing one CH3 group and one OH group (such as eugenol) also scavenge peroxynitrtites and in the process also lower the influx of calcium, it seems to me to be a reasonable possibility.

 

The article on aromatherapy does not provide full citations, but it does point readers to pubmed searches.  You provided a previous link to a well-researched paper on the role of peroxynitrites in a variety of disease including Alzheimer's disease, ALS, multiple sclerosis, Parkinson's disease, some types of cancer, type 2 diabetes, some types of heart disease, and some types of stroke http://physrev.physiology.org/content/87/1/315.full.pdf.  It is not surprising then that aromatherapy using essential oils high in methoxyphenols would be listed in preliminary studies on treating a whole suite of disease.

 

David Stewart is a registered aromatherapist.  Anyone can look up his qualifications on the internet and make a judgment as to whether he is qualified to speak on these matters or not.  Again, I don't endorse all of his ideas. His central argument (as far as we are concerned) is that the molecules in essential oils are very small and they are very concentrated and they enter the brain (whether by smell or some other mechanism).  Again, this would explain why aromatic compounds can both help and hurt the human brain.  

 

It is true that the cited abstract did not explain how the damage to the dopamine receptor was reversed.  No matter what the mechanism, this shows that an antioxidant can at least partially restore the function of a g protein-coupled receptor (I think we can at least agree upon that).  An agonist for the receptor was ineffective, but one antioxidant which scavenges peroxynitrites (tempol) was effective.  http://www.ncbi.nlm.nih.gov/pubmed/18319733   Disruption of g protein coupled receptor occurs in Alzheimer's disease http://www.nature.com/nrn/journal/v12/n2/full/nrn2977.html  and peroxnitrite-mediated damage is widespread in Alzheimer's disease.http://www.jneurosci.org/content/17/8/2653.full http://www.ncbi.nlm.nih.gov/pubmed/11562447You can make the connections or not.

 

I apologize for misquoting you.  In regards to the use of essential oils in the treatment of behavioural issues, perhaps because of differences in research design or because not all behavioural issues are a result of the disease itself, the studies on the effects of essential oils and behavior in Alzheimer's disease are mixed, Does the NIH have anything to say about aromatherapy and/or essential oils in the treatment of symptoms which all Alzheimer's patients exhibit. Several essential oils are peroxynitrite scavengers and here are the essential oils that were effective in the previously discussed small-scale clinical trials: rosemary, lemon, lavender, and orange and tinctures with lemon balm and sage.

 

 

 

 


Lane Simonian
Posted: Thursday, December 22, 2011 10:47 AM
Joined: 12/12/2011
Posts: 4436


Here is some follow up information from last night.  Peroxynitrites oxidize sulfhydryls  

http://www.jbc.org/content/266/7/4244.full.pdf and by doing so they impair the function of g protein-coupled receptors http://cogprints.org/4095/1/Cys_Paper.pdf  Peroxynitrite scavengers are also reducing agents (they add hydrogen back to sulfhydryls) thereby partially restoring the function of g protein-coupled receptors.  These scavengers are thus not only antioxidants, they are also "reverse oxidants."  Essential oils because they are small molecules and because they are highly concentrated can partially reverse the damage caused by peroxynitrites in Alzheimer's disease.  Essential oils high in methoxyphenols and limonene (in citrus-based essential oils) appear to be the best reducing agents.

 

Here in one place is the evidence that peroxynitrite scavengers can partially restore the function of g protein-coupled receptors involved in short-term memory, smell, mood, sleep, social recognition, and behavior (in some cases) in human beings.

http://onlinelibrary.wiley.com/doi/10.1111/j.1479-8301.2009.00299.x/full 

http://jnnp.bmj.com/content/74/7/863.long 

http://www.ncbi.nlm.nih.gov/pubmed/12605619 

http://www.scentsiblesolutions.com/html/texasstate.html 

http://www.ecu.edu/cs-admin/news/newsstory.cfm?ID=947 

https://www.ecu.edu/cs-admin/news/poe/1005/scent.cfm 

http://www.healthboards.com/boards/showthread.php?t=14098 

http://www.alzforum.org/res/for/journal/balin/default.asp 

 

There is more than enough evidence to warrant a larger-scale clinical trial using aromatherapy to treat Alzheimer's disease. This should be done soon, despite the fact that very few people are going to make any money out of this form of treatment.


JAB
Posted: Thursday, December 22, 2011 2:14 PM
Joined: 11/30/2011
Posts: 740


"David Stewart is a registered aromatherapist.  Anyone can look up his qualifications on the internet and make a judgment as to whether he is qualified to speak on these matters or not.  Again, I don't endorse all of his ideas. His central argument (as far as we are concerned) is that the molecules in essential oils are very small and they are very concentrated and they enter the brain (whether by smell or some other mechanism).  Again, this would explain why aromatic compounds can both help and hurt the human brain."

But his central argument is flawed.  Read those references on the factors that affect what can and cannot cross the blood-brain barrier -- written by true experts.

PhD in geophysics -- theoretical seismology.  That explains a lot.  And for a "principle research scientist", Stewart sure doesn't seem to have any publications in peer-reviewed journals.  Nor are any of his writings referenced in any papers in peer-reviewed journals.  His biggest claim to fame seems to be having "spent some 200 hours training with Dr Gary Young, internationally recognized authority on aromatherapy, essential oil production, and the originator of Raindrop Therapy."  Much to my total lack of surprise, Dr Gary Young, Young Living Essential Oils, and the Raindrop Therapy are written up on QuackWatch.  And David Stewart has been getting "courtesy warning letters" from the FDA for making illegal claims for his products.

http://www.quackwatch.com/11Ind/young.html


JAB
Posted: Thursday, December 22, 2011 2:56 PM
Joined: 11/30/2011
Posts: 740


I have no problem with your contention that peroxynitrites are capable of damaging a wide array of proteins, GPCRs included.  What I have a problem with is the contention that peroxynitrite scavengers are capable of directly and selectively reversing the damage done to GPCRs, or that their efficacy is based on direct interaction with damaged GPCRs.  To date, you haven't provided any evidence of that.

And that includes the links you've provided after "Here in one place is the evidence that peroxynitrite scavengers can partially restore the function of g protein-coupled receptors..."  There is no mention of GPCRs in any of these.

The first three papers are ones that I already cited above.  (They are also, as I stated earlier, only very weak evidence that aromatherapy might be beneficial to dementia patients.)

The fourth links to a commercial website, purportedly providing "excerpts" from "the study".  (a) This is almost entirely anecdotal and (b) if there was a successfully-completed study, why wasn't it published?  Possibly the reason is also the same reason why two-thirds of the "facilities" "dropped out" of the study.  

Fourth and fifth links: these are news releases about plans for a study.  I'm not seeing any publications from it, either, and since it was a short study conducted six or seven years ago, if they had publishable results, I'd think they'd have published.  

The next is a brief post from a AD message board.  

The last one is from the Alzheimer Research Forum (a good, professional website) to a live discussion on "The Pathogen Hypothesis".  Did you mean to cite that?  I'm seeing no mention of GPCRs, peroxynitrite, aromatherapy, essential oils...  Mind you, I find the hypothesis that pathogens might play a role in triggering AD quite interesting, and have read quite a bit in the area.  It is, however, still controversial.

I think we can both agree that we'd like to see larger-scale clinical trials, properly designed and executed so as to produce more reliable data.

However, we disagree about your statement that "very few people are going to make any money from this form of treatment" for AD.  Young and Stewart already are, even though there is so little evidence to support its use -- little enough that they've been warned by the FDA to stop making their claims.   There's even less evidence on which to base the selection of the specific treatment protocol to use.
Lane Simonian
Posted: Thursday, December 22, 2011 9:03 PM
Joined: 12/12/2011
Posts: 4436


I am having troubles finding evidence in your links that aromatic compounds do not cross the blood-brain barrier.

The link to the pathogen hypotheis was provided because at the bottom of that page are several case studies regarding the apparent positive effects of antibiotics on Alzheimer's patients(unfortunately the type of antibiotics used is not specified) .  A number of antibiotics are peroxynitrite scavengers

http://informahealthcare.com/doi/abs/10.3109/10715769709097783?2

Short of absolute proof here is the crux of my argument: peroxynitrite-mediated damage is widespread in Alzheimer's disease, g protein-coupled receptor malfunction is a feature of Alzheimer's disease, some antixoxidants (including the peroxynitrite scavenger tempol) partially restore the function of g protein-coupled receptors, and in clinical trials and case studies the use of essential oils (many of which are peroxynitrite scavengers) has improved function in areas related to g protein-coupled receptors (short-term memory, smell, mood, sleep, social recognition, and in some cases behavior). For a very good summary (brought to my attention by Tomek) on the multiple damaging effects of peroxynitrites

see (link removed by Alzheimer's Moderator, as the link was no longer available).  

What I have provided is an explanation for why aromatherapy may be an effective treatment for Alzheimer's disease.  Yes, this is where we agree: more clinical trials are needed.  That the scientific community in the United States has not done them is unfortunate at best.

Lane Simonian
Posted: Friday, December 23, 2011 9:50 AM
Joined: 12/12/2011
Posts: 4436


Small lipophilic compounds can cross the blood-brain barrier http://pubs.acs.org/subscribe/journals/mdd/v05/i06/html/06filmore.html#auth 

and essential oils contain small lipophilic compounds.

http://www.ingentaconnect.com/content/eorc/ijeot/2008/00000002/00000002/art00003 

It is interesting that many of the better peroxynitrite scavengers (cinnamon, clove, peppermint, rosemary, and sage) are potentially the most toxic, but also the least lipophilic.  Maybe this is why at apparently effective doses, they appear not to be toxic to the brain.

 

The one out standing question now is do essential oils reach g protein-coupled receptors in high enough concentrations to reverse the peroxyynitrite caused oxidation of g protein-coupled receptors (and/or g proteins) in the human brain.  I don't think anyone has the direct evidence for this yet.  That is why larger-scale clinical trials with aromatherapy in the treatment of Alzheimer's disease are so crucial.

 


 
× Close Menu