Air pollutants and certain pathogens which initially impair smell can later contribute to Alzheimer's disease due to the formation of peroxynitrites in the hippocampus.
Peroxynitrites also damage muscarinic acetylcholine receptors, nicotinic acetycholine receptors, the transport of choline, and the enzyme acetyltransferase resulting in a critical shortage of acetylcholine--a compound essential for short-term memory,
Since the mid-1990s it has been known that peoxynitrites are critical to the pathogenesis of Alzheimer's disease and since then every study of peroxynitrite scavengers (almost all of them conducted outside of the United States) have partially ameliorated the disease, including a few human clinical trials.
One of the biggest problems is that most peroxynitrite scavengers are natural products that cannot be patented (certain essential oils, for instance) or have already been patented (heat-processed ginseng). Shame on most of the Alzheimer's research community in the United States for ignoring this highly promising path to treating Alzheimer's disease.”
SmartladyDem on Mar 10, 2014 at 15:10:30
“That would be big pharma, and I don't think this is an isolated phenomenon. If they can't make millions they don't even bother trying. It says a lot about humanity.”
relayer on Oct 12, 2013 at 01:01:01
“Thanks for this remarkably informative response. Fanned, etc. Cheers!”
“Here is a short-list of factors that increase peroxynitrite formation: high glucose levels, high blood pressure (especially due to high sodium levels), Down syndrome, the APOE4 gene, presenilin gene mutations, bisphosphonate osteoporosis drugs (such as Fosamax and Boniva), stress, certain chronic bacterial and viral infections, organophosphate pesticides, inorganic mercury, diesel fumes, bisphenols in plastic bottles, smoking, high levels of low density lipoproteins ("bad cholesterol"), and high levels of saturated fats. There is a whole series of dietary, lifestyle, genetic, drugs, and environmental factors that can lead to Alzheimer's disease. That is why the disease is so widespread.”
“How many conditions are there where smell is better through one nostril than the other? And how hard would it be to rule out those other conditions? Probably not many and in most cases quite easily.
It is interesting that people take an amyloid imaging agent seriously when amyloid is not particularly predictive of Alzheimer's disease but find a peanut butter test laughable. Maybe it is because it seems too simple or maybe people find peanut butter funny (probably most smells could be substituted for peanut butter). The people who make fun of Alzheimer's disease on other blogs I don't get--maybe it is just fear or immaturity.
I run into a similar set of problems when I suggest aromatherapy as an effective treatment for Alzheimer's disease. The idea that smell can be used to predict disease or that the chemicals behind smells can be used to treat disease is seen as pseudoscience. But there is a specific scientific explanation for why people with Alzheimer's disease have an altered sense of smell and how chemicals behind odors can partially reverse the disease.”
“Smell through the left nostril appears to give people the ability to name a smell whereas smell through the right nostril produces an emotional response. Thus, my mother with Alzheimer's disease could no longer identify most smells but could say the smell almost knocked her out.
Peroxynitirtes not only damage neurons in the olfactory receptor, they also decrease the release of neurotransmitters involved in short-term memory, mood, sleep, social recognition, and alertness. Furthermore, they inhibit the synthesis of these neurotransmitters, prevent the regeneration of neurons, and cause the death of brain cells.
And here again smell plays a critical role. The olfactory system is connected to the hippocampus. The chemicals responsible for scavenging and partially reversing the damage done by peroxynitrites enter the brain even in the absence of smell per se. Eugenol in rosemary and lemon balm essential oils improve cognition in Alzheimer's patients whereas ferulic acid in lemon balm essential oil improves behavior.
“It is even worse than this. Human clinical trials have been conducted outside of the United States and have demonstrated that a number of natural compounds can partially ameliorate Alzheimer's disease and some other forms of dementia.
With a few exceptions, most Alzheimer's researchers and organizations in the United States are seeking a pharmaceutical solution to this disease, ignoring the fact that the disease is most effectively treated with compounds found in plants. This is a tragedy of the highest order.”
Several of the risk factors for Alzheimer's disease including high glucose levels, high blood pressure due to high sodium levels, and Down Syndrome all contribute to high levels of myo-inositol in the brain. High levels of myo-inositol result in the formation of amyloid plaques and more importantly to the main cause of Alzheimer's disease: a toxic oxidant and nitrating agent called peroxynitrites. Among the compounds that scavenge peroxynitrites and reverse part of their oxidative and nitrative damage to critical receptors, transport systems, enzymes, and neurotransmitters in the brain is curcumin. More bioavailable and absorbable forms of curcumin have shown effectiveness in animal studies and have begun to be studied in humans.
“Not all natural supplements will improve memory or delay the onset of Alzheimer's disease, but some will. A Mediterranean diet high in phenolic compounds and Omega 3-fatty acids (such as fish oil) and an Indian diet high in various spices and herbs (containing phenols) will likely not only delay the onset of Alzheimer's disease but will slow down the progression of the disease (and in some cases partially reverse it).
Rosemary essential oil (and several other essential oils such as clove, bay laurel, and basil) contains a compound called eugenol that not only improves memory in health adults, it also leads to significant improvement in cognition in people with demetia.
Phenolic compounds inhibit the formation of peroxyntrites, scavenge peroxynitrites, and repair part of their damage. They add hydrogen back to receptors invovled in short-term memory, smell, sleep, alertness, social recognition and brain growth and convert peroxynitrites into water and a nitrite anion. Water in turn partially reverses the nitration of NMDA receptors and thus reduces inflammation by limiting the efflux of glutatmate and protects neurons against death by inhibiting the influx of calcium. Water also partially reverses the nitration of tau proteins allowing for better neurotransmission. Indeed almost every aspect of Alzheimer's disease is potentially reversible.
I like to point to the studies on aromatherapy with rosemary essential oil and heat-processed ginseng because they provide two cases in which compounds containing high levels of methoxyphenols (which are excellent peroxynitrite scavengers) have partially reversed Alzheimer's disease in human clinical trials. Eugenol in essential oils, however, can potentially increase agitation in some Alzheimer's patients whereas the ferulic acid in heat-processed ginseng (and also in coconut oil) may reduce agitation. Heat-processed ginseng is patented and expensive but steaming ginseng for 3 hours may produce similar results. Most essential oils cost about $10 a bottle. They both provide an effective treatment for Alzheimer's disease.”
Mar 31, 2013 at 18:16:16
“Many phenolic compounds, including tea polyphenols, will cross the blood-brain barrier, but are rapidly metabolized or not well aborbed well into the bloodstream (curcumin, for instance) or not well absorbed into the fatty tissue in the brain (ferulic acid, for instance).
The best compounds for treating Alzheimer's disease are methoxyphenols (such as curcumin, ferulic acid, and eugenol). Methoxyphenols not only effectively scavenge peroxynitrites--the prinicipal oxidant in Alzheimer's disease--they also partially restore function to receptors and enzymes that affect short-term memory, sleep, mood, alertness, social recognition, neurotransmissions, brain growth, and neuronal survival. A combination of stimulating essential oils such as rosemary (which contains eugenol) and lemon and relaxing essential oils (orange and lavender) via aromatherapy led to significant improvements in cognitive function in Alzheimer's patients without negative side effects (such as an increase in agitation).
Heat-processed ginseng which contains the methoxyphenols ferulic acid, syringic acid, and vanillic acid significantly improved cognition and non-cognitive function in people with moderately severe Alzheimer's disease.
Researchers are working on ways to make curcumin and ferulic acid more bioavailabe, which may be the key to treating Alzheimer's disease.”
sealift on Mar 31, 2013 at 18:26:43
“Good summary. And there are a good number of peer-reviewed studies,
with humans, with evidence for reduced cognitive impairment and
improved mood with eg green tea . Polyphenols are a possible factor. Since
we don't really know the mediating variables it is best to take the
nutrients as whole foods versus extracts. An exception might be
grape/grape seed extract resveratrol.”
“The components in Souvenaid may have some positive effects, but the best way to treat Alzheimer's disease is with peroxynitrite scavengers that partially reverse the oxidation of receptors involved in short-term memory, mood, sleep, smell, social recognition, alertness, and brain growth, reconstitute tau proteins for proper neurotransmission, inhibit the influx of calcium which kills neurons, and improves the transport and metabolism of glucose to reduce delusions, wandering, and apathy. The peroxynitrite scavenger eugenol in rosemary essential oil via aromatherapy and ferulic acid, syringic acid, vanillic acid, and p-coumaric acid in heat-processed ginseng respectively led to significant improvements in cognitive function related to personal orientation and significant improvements in cogntive and non-cognitive function in people with moderate to moderately severe Alzheimer's disease in small-scale clinical trials:
Conclusions: In conclusion, we found aromatherapy an efficacious non-pharmacological therapy for dementia. Aromatherapy may have some potential for improving cognitive function, especially in AD patients.
“Alzheimer's disease can potentially be prevented and treated. Omega 3-fatty acids and phenolic compounds in various fruits, vegetables, nuts, spices, and essential oils can at least delay the onset of Alzheimer's disease.
Phenolic compounds inhibit the activation of phospholipase C gamma and Omega 3-fatty acids inhibit the activity of both phospholipase C gamma and beta. These are the two enzymes which likely trigger Alzheimer's disease (mercury and aluminium fluoride also activate phospholipase C).
Phenolic compounds also scavenge and repair part of the damage done by the main oxidant in Alzheimer's disease: peroxynitrites. That is why a Mediterranean diet or an Indian diet slows the progression of Alzheimer's disease.
Curcumin is an excellent peroxynitrite scavenger, but it does not enter the bloodstream well. Researchers at UCLA have developed a more bioavailable form of curcumin (Longvida) that has completely reversed memory deficits in mice.
Clinical trials have just begun to see the effects in human beings. Clinical trials with other compounds containing peroxynitrite scavengers such as rosemary essential oil (via aromatherapy), a carefully prepared tincture of lemon balam/Melissa officinalis essential oil, and heat-processed ginseng have already led to significant improvements in cognitive and non-cogntive function in people with Alzheimer's disease.”
“The fatalism and misplaced inferences regarding this disease are often amazing. Phenolic compounds in various fruits (especially berries), nuts, vegetables, spices, and essential oils inhibit one of the of the two forms of the enzyme that trigger Alzheimer's disease--phospholipase C gamma (mercury and aluminium fluoride also activate phospholipase C). Omega 3 fatty acids inhibit the activity of both enzymes. The combination of the two likely prevent or at least delay the onset of Alzheimer's disease.
Phenolic compounds not only delay the onset of Alzheimer's disease but through a Mediterranean diet or a diet from India they slow down the progression of the disease. They do so by scavenging and repairing the damage done by the main oxidant in Alzheimer's disease--peroxynitrites.
Clinical trials have just begun to see what effect this form of curcumin will have on human beings. Clinical trials using essential oils (aromatherapy and carefully prepared tinctures) and heat processed-ginseng containing peroxynitrite scavengers have already improved cognitive functions in Alzheimer's patients.”
“I am going to put this as cynically as possible: there are two groups of people: those interested in finding a cure for Alzheimer's disease and those interested in funding a cure for Alzheimer's disease. The first group is composed of caregivers and people with Alzheimer's disease. The second group includes Alzheimer's organizations, Alzheimer's researchers, and government officials. For the first group of people finding a cure for Alzheimer's disease is a matter of survival. For the latter, finding a cure for Alzheimer's disease would put them out of work.
In the late 1990s, scientist discovered that peroxynitrite-mediated damage was widespread in Alzheimer's disease. Since then, scientists almost all of them working outside of the United States found that various peroxynitrite scavengers-nearly all of them from natural products-- ameliorated Alzheimer's disease either in mice or human beings.
It will take a herculean effort to effectively treat Alzheimer's disease not because more money is required but because those involved in funding a cure for Alzheimer's disease are not fundamentally intersted in understanding the disease nor treating it.”
Sep 27, 2012 at 11:50:25
“There are three types of receptors in the brain whose activation can trigger Alzheimer's disease: epidermal growth factor receptors, platelet derived growth factor receptors, and g protein-coupled receptors. All three contribute to the formation of peroxynitrites which is implicated in both Alzheimer's disease and various forms of cancer. As Alzheimer's disease progresses, peroxynitrites inhibit all three receptors so the cancer medication would become ineffective. To delay the onset of Alzheimer's disease, phenolic compounds in various fruits, vegetables, spices, and essential oils can be used to inhibit the first two types of receptors.
Through the oxidation and nitration of cricial receptors, transport systems,and proteins in the brain, peroxynitries cause the loss of short-term memory, depression, sleep distrubances, a decline in alertness and awareness, and the death of neurons. Effective peroxynitrites scavengers limit the formation of peroxynitrites, detoxify them, and repair part of the damage they do to the brain. They thus not only stop the progression of Alzheimer's disease, they partially reverse it. The most effective peroxynitrite scavengers are methoxyphenols, such as eugenol in various essential oils and ferulic acid, vanillic acid, p-coumaric acid, and syringnic acid in sun gingseng (heat- processed panax ginseng). Both have been used to improve cognitive function in Alzheimer's patients.
Aug 14, 2012 at 21:48:28
“Cocoa is one of several flavonoids that may help delay the onset of Alzheimer's disease. The following article provides further support for the dictum that anything that inhibits the formation of peroxynitrites delays the onset of Alzheimer's disease (through oxidation and nitration, peroxynitrites damage a whole series of transport systems, enzymes, proteins, and neurotransmitter receptors in the brain of Alzheimer's patients and causes the death of neurons), anything the stops the formation of peroxynitrites stops the progression of Alzheimer's disease, and anything that partially repairs the damage done by peroxynitrites partially reverses Alzheimer's disease.
The best compounds for treating Alzheimer's disease are those containing methyls (which bind to peroxynitrites) and at least one phenol (which inhibit peroxynitrite formation, scavenge peroxynitrites, and reverse part of their damage). These include eugenol, thymol, and carvacrol which are highly concentrated in various essential oils (such as bay laurel, clove, cinnamon leaf, rosemary, sage, and thyme) and can be inhaled directly into the part of the brain most damaged by peroxynitrites--the hippocampus.
May 20, 2012 at 13:14:26
“This is all correct. In this case of Alzheimer's disease, the good form of nitric oxide is replaced by the bad form of nitric oxide (inducible nitric oxide). Inducible nitric oxide combines with superoxide anions to form peroxynitrites. Peroxynitrites contibute to the formation of amyloid plaques, to the aggregation of amyloid plaques, to the hyperphosphoyrlation of tau proteins, to the oxidation of receptors involved in short-term memory, mood, sleep, social recognition alertness, awareness, and smell, and to the activation of NMDA receptors which leads to the influx of calcium and the efflux of glutamate both of which kills neurons. This is why every peroxynitrite scavenger (spices, essential oils, other botanical extracts, etc.) ever tested in various models of Alzheimer's disease has partially reversed the disease.”
Ian Welch on May 21, 2012 at 11:52:40
“Thank you. I will explore your input. Regards,Ian ”
May 19, 2012 at 23:03:10
“The 2025 deadline is about 13 years too late. The key to treating Alzheimer's disease is with compounds that contain methyl groups and hydroxyl groups (phenols, for instance). This includes eugenol, carvacrol and thymol (contained in various essential oils) and bexarotene. The advantage that the first three have over bexarotene is that they directly reach the brain via aromatherapy, they are much cheaper, they have fewer side effects, and they can be used immediately. All the medicines currently prescribed to treat Alzheimer's disease contain methyl groups but almost none of them contain hydroxyl groups. By being good hydrogen donors, methoxyphenols neutralize the toxin responsible for Alzheimer's disease (peroxynitrites) and partially restore the function of receptors, enzymes, and other proteins involved in short-term memory, sleep, mood, alertness, social recognition, awareness, and smell. They inhibit and perhaps reverse the nitration of proteins that contribute to the formation of amyloid plaques, the aggregation of amyolid plaques, and to neurofibrillary tangles. In short, methoxyphenols contained in various essential oils stop and partially reverse the progression of Alzheimer's disease.
“When the history of Alzheimer's disease is finally written, it will likely show how many very smart people in the pharmaceutical industry, research organizations, and Alzheimer's funding organizations led us down the wrong path. According to a report in the New York Times, over 30 percent of autopsies showed high levels of amyloid plaque in individuals who did not have Alzheimer's disease. And Eli Lilly who keeps insistently pushing for its anti-amyloid drug found that a quarter of the people in its initial study did not have amyloid, but (although the pharmaceutical giant will not acknowledge this) likely had Alzheimer's disease.
Alzheimer's disease is not caused by amyloid, it is caused by peroxynitrites. People with only the amyloid precursor protein can have Alzheimer's disease.
And if you want to treat Alzheimer's disease use peroxynitrite scavengers such as heat-processed ginseng, and rosemary and lemon balm essential oils. Otherwise, you are just going further down the rabbit hole.”
Oct 6, 2013 at 22:09:26
“Alzheimer's disease is caused by a potent oxidant called peroxynitrite. Peroxynitrites inhibit the synthesis and release of neurotransmitters involved in short-term memory, sleep, mood, social recognition, and alertness. They contribute to tissue damage, vascular dysfunction, and the reduced transport of glucose in the brain. They inhibit the regeneration of neurons and trigger the death of brain cells.
This is a partial list of factors that contribute to the formation of peroxynitrites in the brain: high glucose levels, high blood pressure (especially due to high sodium levels), high levels of saturated fats, low density lipoproteins ("bad cholesterol"), Down syndrome, the APOE4 gene, presenilin mutations, bisphosponate osteoporosis drugs. such as Fosamax, stress, certain chronic bacterial and viral infections, mercury, organophosphate pesticides, diesel fumes, and bisphenols in plastics. A whole range of dietary, genetic, and environmental factors can thus contribute to Alzheimer's disease. A diet high in phenolic compounds found in various spices, fruits, and vegetables and omega 3-fatty acids reduce the risk for Alzheimer's disease because they inhibit the formation of peroxynitrites. There is no absolute way to prevent the disease but there are ways to lower risk.”
“The easiest to find are essential oils. They can be bought from health food stores or online (Ananda apothecary in Boulder and Dandelion Botanical Company in Seattle have good reputations for having pure essential oils).
The easiest and perhaps most effective way of using the essential oils is through direct inhalation--sniffing a few of the oils twice a day for a few seconds. Some of the oils that increase cognition can increase anxiety and blood pressure in some individuals with Alzheimer's disease. Allergic reactions are also possible (headaches, nausea, wheezing). In general, however, they are safe to use.
The following oils should improve cognition: bay laurel, clove, rosemary, nutmeg, basil, cinnamon leaf, lemon balm, and coriander. The following oils can be used for relaxation:
orange, lavender, lemon balm, patchouli, rose, and Ylang Ylang.
Heat-processed (sun) ginseng is a patented product. It is produced by a complicated process of steaming and dry heat. There is a supplier in Long Beach, but a month's supply costs about $700. Steaming white (Panax) ginseng for about three hours, though, may produce similar results.
Feru-guard is sold in Japan, but can also be bought outside of Japan (en.kenko.com). Angelica archangelica itself can be bought at health food stores. If interested, I would start with the essential oils and then try to steam ginseng.”
“Peroxynitrite scavengers have partially reversed Alzheimer's disease in vitro, in mice, and in "men." The following are links to human clinical trials that Alzheimer's research centers such as Banner should be replicated on a larger scale. It is not a lack of money or participants in clinical trials that is delaying an answer for this disease; it is the insistence that only drugs will be able to treat the disease.
Eugenol in rosemary essential oils and geraniol in lemon essential oil via aromatherapy (lavender and orange were used at night for relaxation).
“The message coming out of may research facilities is both discouraging and incorrect: past a certain point the damage done to the brain is so great that nothing can be done to help people with Alzheimer's disease. This is the explanation given for why amyloid-reducing drugs have produced such disappointing results: the drugs had to be given earlier perhaps even before there are symptoms of the disease.
Many researchers, organizations, and pharmaceutical companies are staking a great deal on the amyloid hypothesis. The problem, however, is that it is largely the wrong hypothesis for the disease.
Alzheimer's disease is primarily caused by a potent oxidant called peroxynitrite. Peroxynitrites inhibit the synthesis and release of neurotransmitters affecting short-term memory, sleep, mood, smell, social recognition, and alertness; damages cell membranes, causes vascular damage, inhibits the regeneration of neurons in the hippocampus, and contributes to the death of neurons. The good news is that the damage done by peroxynitrites can be at least partially reversed during any stage of Alzheimer's disease.”
“Medicare made the right decision. Amyloid is not the cause of Alzheimer's disease. In about one-third of all autopsies, people had significant amounts of amyloid in their brains, but did not have Alzheimer's disease. Eli Lilly reported in its initial trials of solanezumab that 25% percent of those tested either did not have amyloid or Alzheimer's disease (and many of those likely had Alzheimer's disease without amyloid). People with only the amyloid precursor protein can have Alzheimer's disease.
The best biomarker for the likely onset of Alzheimer's disease is myo-inositol.
People with high glucose levels, high blood pressure due to high sodium levels, and Down syndrome all have high myo-inositol levels in their brain and this leads to an increased risk for Alzheimer's disease.
The phospholipase C hydrolysis of phosphatidyl (myo)-inositol 4,5 biphosphate leads to the release of intracellular calcium and the formation of amyloid plaques. Phospholipase C also activates protein kinase C and p38 MAPK, which results in the formation of peroxynitrites. Peroxynitrites inhibit the synthesis and release of neurotransmitters involved in short-term memory, sleep, mood, smell, social recognition and alertness, and they impede the regeneration of neurons in the hippocampus and contributes to the death of neurons. Peroxynitrites , not amyloid plaques, are the true cause of Alzheimer's disease.”