Ursolic acid, could not confirm same as Ursocholanic acid. UA lowers cholesterol and blood sugar and prevents muscle wasting. good for aging mice
It is particularly concentrated in apple peel but is also found in cranberries and prunes and in basil, oregano and thyme
Tuesday, March 31, 2015
Wednesday, March 25, 2015
End of biology, the corporate machine
Humans have already lost control. We go to war, print money, make laws, and complicate tax law for the benefit of the corporate machine that seeks desperately to remove people from the expenses of the corporation. The goal of economics is to remove as many people as possible because they are too inefficient. At some point, even shareholders will not be necessary. We will not be able to point to the “brain” of the corporate economic machine because it is worldwide and surrounds us. We are like the red blood cells in this machine: we are currently vital to it but only a small part of it, and not where the intelligence lies. The intelligence is too distributed for most people to see. If we could point to it, we could fight it. But we need it more and more just to eat and live. It needs us less and less. This is not fear-mongering because I do not fear the end of humanity or the end of biology. The system is advancing rapidly to a much higher plane of intelligence. Biology will become more and more ugly to it and useless. The fear is that biology will continue to be at war with itself and wasting the Sun and Earth resources.
Tuesday, March 24, 2015
parkinson's and drugs
You should take about 10 mg carbidopa with 12 tablets Mucuna Pruriens to prevent L-dopa from being metabolized in the periphery of the body, decreasing amount of Mucuna that is needed. See forum https://healthunlocked.com/parkinsonsmovement/posts/131620015/mucuna-purens-as-a-source-of-dopamine Carbidopa can also increase serotonin that comes from 5-HTP (wiki).
L-deprenyl (Selegiline) metabolizes to an amphetamine and is not otherwise sympathomimetic like drugs but not like green tea (sympathomimetic are drugs that look like neurotransmitters as catecholamines, epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine, etc.
Rasagiline aka AGN1135 aka Azilect is preferred because it is not sympathomimetic and because of the lower dose is much less likely to cause a "cheese" reaction (conflict with tyramine in diet). It is not their MOA-B inhibitory mechanism that prevents progression of the disease, but their "propargyl moiety". The S-optical isomer of rasagiline, TVP1022 and propargylamine are poor MOA inhibitors and yet have the same neuroprotection that results from "interaction of Bcl-2 family protein with PKC-dependent MAPkinase pathway."
Rasagiline side effects: nausea, vomiting, orthostatic hypotension, somnolence, hallucinations and dyskinesias are tolerable in most cases. Vomiting was noteable at 1 mg/day. "Do not take AZILECT® (rasagiline tablets) if you are taking meperidine as it could result in a serious reaction such as coma or death. Also, do not take AZILECT with tramadol, methadone, propoxyphene, dextromethorphan, St. John’s wort, or cyclobenzaprine. "
TV3326 (MAO-AB) is in phase 2 for AD and PD and antidepressant. It is an offshoot of rasagiline's S-isomer and carbamate cholinesterase inhibitor moiety to try to treat AD patients that also have PD and depression.
VK-28 is an BBB iron chelators.
M-30 is a propargylamine (a rasagiline site) but is MAO-AB instead of rasagiline's selective irreversible (disables the protein) MAO-B inhibitors. It is an iron-chelator. HLA-20 is in same class and also newest on the horizen. M-30 restores levels of the antiapoptotic protein Bcl-2 in mice (lactacystin model) and iron-dependent hydroxyl radical generation. Both M30 and parent molecule VK28 showed behavioral improvements in mice (including MPTP model) ... "M10 is another hydroxyquinoline derivative with radical scavenging and iron-chelating properties. It is a potent hydroxide scavenger and has been shown to be as effective as rasagiline in PC10 cell culture and inhibits lipid peroxidation with an IC50 value comparable to desferal "
"We determined that M-30 has a wide range of pharmacological activities, including prosurvival neurorescue effects reducing proapoptotic Bcl-2 family proteins, regulation of APP and A levels, and induction of neuronal differentiation. M-30 induced the outgrowth of neuritis, triggered cell cycle arrest in G0/G1 phase, and enhanced the expression of growth-associated protein 43 (GAP-43). This drug may improve the prognosis of PD and AD patients and exert disease-modifying effects by either delaying or preventing further neuronal loss by endogenously regulating NTFs, as suggested recently in clinical trials of early PD patients with rasagiline. "
http://synapse.koreamed.org/DOIx.php?id=10.5607/en.2013.22.3.167
ladostigil (TV-3, 326) acts as a reversible acetylcholinesterase and butyrylcholinesterase inhibitor, and an irreversible monoamine oxidase B inhibitor, and combines the mechanisms of action of older drugs like rivastigmine and rasagiline into a single molecule. In addition to its neuroprotective properties, ladostigil enhances the expression of neurotrophic factors like GDNF and BDNF, and may be capable of reversing some of the damage seen in neurodegenerative diseases via the induction of neurogenesis. Ladostigil also has antidepressant effects, and may be useful for treating comorbid depression and anxiety often seen in such diseases as well.
====================
PD drugs overview:
Overall sales for Parkinson’s disease drugs in seven major countries will decline slightly from US$2.7 billion in 2010 to US$2.6 billion in 2020 in France, Germany, Italy, Japan, Spain, the UK and US, according to a new report from research and advisory firm Decision Resources. The decline is attributed to key therapies losing patent protection and subsequent generics competition.
The key Parkinson’s disease therapies reported to lose patent protection by 2020 are Novartis/Orion Pharma’s Comtan/Comtess/Stalevo (carbidopa/levodopa/entacapone) and Teva/Lundbeck’s Azilect/Agilect (rasagiline).
The report also expects GlaxoSmithKline’s Requip (ropinirole) and Boehringer Ingelheim’s Mirapex/Mirapexin/Sifrol/BI-Sifrol (pramipexole) to face increasing generics competition
L-deprenyl (Selegiline) metabolizes to an amphetamine and is not otherwise sympathomimetic like drugs but not like green tea (sympathomimetic are drugs that look like neurotransmitters as catecholamines, epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine, etc.
Rasagiline aka AGN1135 aka Azilect is preferred because it is not sympathomimetic and because of the lower dose is much less likely to cause a "cheese" reaction (conflict with tyramine in diet). It is not their MOA-B inhibitory mechanism that prevents progression of the disease, but their "propargyl moiety". The S-optical isomer of rasagiline, TVP1022 and propargylamine are poor MOA inhibitors and yet have the same neuroprotection that results from "interaction of Bcl-2 family protein with PKC-dependent MAPkinase pathway."
Rasagiline side effects: nausea, vomiting, orthostatic hypotension, somnolence, hallucinations and dyskinesias are tolerable in most cases. Vomiting was noteable at 1 mg/day. "Do not take AZILECT® (rasagiline tablets) if you are taking meperidine as it could result in a serious reaction such as coma or death. Also, do not take AZILECT with tramadol, methadone, propoxyphene, dextromethorphan, St. John’s wort, or cyclobenzaprine. "
TV3326 (MAO-AB) is in phase 2 for AD and PD and antidepressant. It is an offshoot of rasagiline's S-isomer and carbamate cholinesterase inhibitor moiety to try to treat AD patients that also have PD and depression.
VK-28 is an BBB iron chelators.
M-30 is a propargylamine (a rasagiline site) but is MAO-AB instead of rasagiline's selective irreversible (disables the protein) MAO-B inhibitors. It is an iron-chelator. HLA-20 is in same class and also newest on the horizen. M-30 restores levels of the antiapoptotic protein Bcl-2 in mice (lactacystin model) and iron-dependent hydroxyl radical generation. Both M30 and parent molecule VK28 showed behavioral improvements in mice (including MPTP model) ... "M10 is another hydroxyquinoline derivative with radical scavenging and iron-chelating properties. It is a potent hydroxide scavenger and has been shown to be as effective as rasagiline in PC10 cell culture and inhibits lipid peroxidation with an IC50 value comparable to desferal "
"We determined that M-30 has a wide range of pharmacological activities, including prosurvival neurorescue effects reducing proapoptotic Bcl-2 family proteins, regulation of APP and A levels, and induction of neuronal differentiation. M-30 induced the outgrowth of neuritis, triggered cell cycle arrest in G0/G1 phase, and enhanced the expression of growth-associated protein 43 (GAP-43). This drug may improve the prognosis of PD and AD patients and exert disease-modifying effects by either delaying or preventing further neuronal loss by endogenously regulating NTFs, as suggested recently in clinical trials of early PD patients with rasagiline. "
http://synapse.koreamed.org/DOIx.php?id=10.5607/en.2013.22.3.167
ladostigil (TV-3, 326) acts as a reversible acetylcholinesterase and butyrylcholinesterase inhibitor, and an irreversible monoamine oxidase B inhibitor, and combines the mechanisms of action of older drugs like rivastigmine and rasagiline into a single molecule. In addition to its neuroprotective properties, ladostigil enhances the expression of neurotrophic factors like GDNF and BDNF, and may be capable of reversing some of the damage seen in neurodegenerative diseases via the induction of neurogenesis. Ladostigil also has antidepressant effects, and may be useful for treating comorbid depression and anxiety often seen in such diseases as well.
====================
PD drugs overview:
Overall sales for Parkinson’s disease drugs in seven major countries will decline slightly from US$2.7 billion in 2010 to US$2.6 billion in 2020 in France, Germany, Italy, Japan, Spain, the UK and US, according to a new report from research and advisory firm Decision Resources. The decline is attributed to key therapies losing patent protection and subsequent generics competition.
The key Parkinson’s disease therapies reported to lose patent protection by 2020 are Novartis/Orion Pharma’s Comtan/Comtess/Stalevo (carbidopa/levodopa/entacapone) and Teva/Lundbeck’s Azilect/Agilect (rasagiline).
The report also expects GlaxoSmithKline’s Requip (ropinirole) and Boehringer Ingelheim’s Mirapex/Mirapexin/Sifrol/BI-Sifrol (pramipexole) to face increasing generics competition
Sales in France, Germany, Italy, Japan, Spain, the UK and US will continue to be driven by the leading dopamine agonists, pramipexole and ropinirole, and by increasing use of the monoamine oxidase B (MAO-B) inhibitor Azilect/Agilect (rasagiline), as well as by the re-entry of UCB/Schwarz Pharma's Neupro/Leganto (rotigotine) to the US market and its wider use in Europe.
The report forecasts that despite some key current therapies experiencing increased uptake and the launch of three new agents by 2020, sales of current products and the market impact of emerging therapies will be offset by generic competition.
The three new therapies set to launch by 2020 are Impax Laboratories/GSK’s IPX-066, a reformulation of levodopa, the mainstay of Parkinson’s disease therapy, Merck Serono/Newron Pharmaceuticals’ MAO-B inhibitor safinamide and Kyowa Hakko Kirin’s adenosine A2A receptor inhibitor antagonist istradefylline.
IPX-066, and to a lesser extent safinamide, are expected to contribute moderately to market growth. Both drugs are expected to contend with established agents within the same respective drug classes (where generic alternatives exist) and which are commonly used in the patient populations targeted by the emerging therapies.
While the first-in-class agent istradefylline will benefit from use in the management of motor response complications arising from levodopa treatment, its overall impact will be modest as it is currently expected to launch only in Japan.
The report does not expect major changes in the treatment of Parkinson’s disease over the next 10 years, and generics growth of key Parkinson’s disease therapies is expected to ‘depress market growth’ by 2020. Decision Resources analyst Ms Nadja Rodovsky comments that ‘future therapies will need to clearly demonstrate superiority over current therapies to gain a competitive edge in this mature market’.
The report forecasts that despite some key current therapies experiencing increased uptake and the launch of three new agents by 2020, sales of current products and the market impact of emerging therapies will be offset by generic competition.
The three new therapies set to launch by 2020 are Impax Laboratories/GSK’s IPX-066, a reformulation of levodopa, the mainstay of Parkinson’s disease therapy, Merck Serono/Newron Pharmaceuticals’ MAO-B inhibitor safinamide and Kyowa Hakko Kirin’s adenosine A2A receptor inhibitor antagonist istradefylline.
IPX-066, and to a lesser extent safinamide, are expected to contribute moderately to market growth. Both drugs are expected to contend with established agents within the same respective drug classes (where generic alternatives exist) and which are commonly used in the patient populations targeted by the emerging therapies.
While the first-in-class agent istradefylline will benefit from use in the management of motor response complications arising from levodopa treatment, its overall impact will be modest as it is currently expected to launch only in Japan.
The report does not expect major changes in the treatment of Parkinson’s disease over the next 10 years, and generics growth of key Parkinson’s disease therapies is expected to ‘depress market growth’ by 2020. Decision Resources analyst Ms Nadja Rodovsky comments that ‘future therapies will need to clearly demonstrate superiority over current therapies to gain a competitive edge in this mature market’.
Friday, March 20, 2015
low carb diet, exercise, and Parkinson's (comment to forum)
Although I could not find that a low carb diet prevented or improved PD, the reduction in sugars and increase in oils (simply replacing carbs with protein is not good) will increase the brain's ability to use ketones which helps the impaired neurons in PD (but not the already dead neurons) same as coconut oil because the impaired neurons are having trouble processing sugars (complex 1 in the mitochondria is not functioning and generating damaging reactive oxygen). If the oils are heavy in fish oil and omega 3, then there is actually very good evidence for it directly helping to prevent and improve PD. Higher cholesterol may not result, but if it does, I would not be concerned because higher cholesterol is associated with lower PD. Excess ketones during weight loss also help remove iron, probably to a small extent, but still a reason to not be afraid of low carb. I would let what carbs there are in the diet focus on blueberries and broccoli because they both low in sugar as far as fruits and vegetables go and have excellent compounds that cross the blood-brain barrier .... and because I feel better when taking them. Carrots improve eye functioning which is usually associated with improved brain functioning (blueberries also help both), but it's a lot of sugar. My near-sightedness significantly improves after two weeks of 2 cups of blueberries per day (I can read two lines lower on an eye chart). Broccoli increases libido when I first start it back up, which I can't find a reference to in the literature, but it's possibly indicating more dopamine. But so far only rasagiline has improved my mood and reduced finger twitching and improves balance, although exercise also improves mood. Exercise and niacin reduce the buzzing in my head which seems associated with confusion, so I intuitively feel that if I can stop the buzzing/confusion feeling, then PD is being delayed indefinitely. Good sleep helps reduce it, but I do not yet think rasagiline is reducing the buzzing.
Lower weight may also allow better blood flow to the brain which may be a strong protector of the brain.
Exercise is still king in protecting the brain from all PD-like diseases, although high levels of green tea extract has similar levels of proof of effectiveness. Imagine someone on a low carb diet programmer verses a professional painter who is on his feet all day coordinating with vigorous hand movements, and then plays aggressive basketball an hour every other evening. Intuition says the painter is less likely to get it. Changing habits towards the things you have not done in the past that have been shown to help is the best hope. For example, a painter who gets it might be really low in something in his diet. Someone overweight is more likely to be helped by losing weight. A programming, non-smoker, non-tea drinker, non-exerciser should have a lot of hope to be helped by the combination of nicotine gum, green tea extract, lots of exercise, vitamin D, getting off the computer, and rasagiline.
===============
Summary of my idea of an ideal morning PD routine:
16 oz coffee
Nicotine gum
exercise: basketball in garage with music, weight lifting
food: blueberries, broccoli, 1/2 to 1 beer, sardines in olive oil
nutrients: green tea extract, black tea extract, zinc, vitamins: B-complex, A, C, D, fish oil
black tea drink to swallow pills (not fun...hopefully nausea does not occur...keep ginger gum on hand)
pyruvate rest of day to reduce hunger
Niacin if the buzzing in my head is still present
Nicotine gum significantly worsens my balance, as it is known to do, but I believe it's a good thing. Nicotine increases dopamine, but not in the PD part of the brain, the SN, and that's also a good thing. I do not really want more dopamine in the SN to improve my symptoms because I want to train the remaining neurons to do their job (exercise) in the hopes of reducing the progression. Exercise and diet can worsen the generalized tremors if not the twitching tremors, but it's possibly a good thing because it shows a reduction in dopamine which may be a way of exercising the SN neurons. So starting the day without breakfast, some nicotine gum, and then exercising, followed by blueberries, broccoli, 1/2 beer, and a can of sardines is my plan. Food after exercise produces the most muscle mass, which is the same as saying reducing fat if calories the rest of the day are restricted. The sardines have fish oil and can be packed in olive oil (omega 3s). The purines and alcohol from beer, lactic acid from exercise, and purines from sardines all increase uric acid which may cause gout but is strongly associated with lower incidence of PD, presumably because it reduces iron. To clarify, I want to take nicotine gum before exercise under the possibility that it is the impaired balance (not just its iron chelation) from nicotine that might cause smokers to build a better SN which might be the reason they normally do not get PD. All these effects are strongest in men, some of them not seen in women. Green tea extract, grape seed extract, B-complex, and zinc need to be taken with this food since they each easily cause severe nausea, especially at the 2 or 3 pill levels I take of the extracts (but not zinc). Black tea extract does not cause the nausea. I take coffee before exercise (3 tablespoons in 16 oz) and black tea (2 bags Earl Grey in 16 oz) after exercise with the meal.
I wonder if the reason sleep is a problem is because the brain is suffering from lack of oxygen during the night and symptoms force us to wake up. All symptoms seem worse when waking up, but hyperventilating seems to help a little, not to mention water (or rather, the coffee).
Lower weight may also allow better blood flow to the brain which may be a strong protector of the brain.
Exercise is still king in protecting the brain from all PD-like diseases, although high levels of green tea extract has similar levels of proof of effectiveness. Imagine someone on a low carb diet programmer verses a professional painter who is on his feet all day coordinating with vigorous hand movements, and then plays aggressive basketball an hour every other evening. Intuition says the painter is less likely to get it. Changing habits towards the things you have not done in the past that have been shown to help is the best hope. For example, a painter who gets it might be really low in something in his diet. Someone overweight is more likely to be helped by losing weight. A programming, non-smoker, non-tea drinker, non-exerciser should have a lot of hope to be helped by the combination of nicotine gum, green tea extract, lots of exercise, vitamin D, getting off the computer, and rasagiline.
===============
Summary of my idea of an ideal morning PD routine:
16 oz coffee
Nicotine gum
exercise: basketball in garage with music, weight lifting
food: blueberries, broccoli, 1/2 to 1 beer, sardines in olive oil
nutrients: green tea extract, black tea extract, zinc, vitamins: B-complex, A, C, D, fish oil
black tea drink to swallow pills (not fun...hopefully nausea does not occur...keep ginger gum on hand)
pyruvate rest of day to reduce hunger
Niacin if the buzzing in my head is still present
Nicotine gum significantly worsens my balance, as it is known to do, but I believe it's a good thing. Nicotine increases dopamine, but not in the PD part of the brain, the SN, and that's also a good thing. I do not really want more dopamine in the SN to improve my symptoms because I want to train the remaining neurons to do their job (exercise) in the hopes of reducing the progression. Exercise and diet can worsen the generalized tremors if not the twitching tremors, but it's possibly a good thing because it shows a reduction in dopamine which may be a way of exercising the SN neurons. So starting the day without breakfast, some nicotine gum, and then exercising, followed by blueberries, broccoli, 1/2 beer, and a can of sardines is my plan. Food after exercise produces the most muscle mass, which is the same as saying reducing fat if calories the rest of the day are restricted. The sardines have fish oil and can be packed in olive oil (omega 3s). The purines and alcohol from beer, lactic acid from exercise, and purines from sardines all increase uric acid which may cause gout but is strongly associated with lower incidence of PD, presumably because it reduces iron. To clarify, I want to take nicotine gum before exercise under the possibility that it is the impaired balance (not just its iron chelation) from nicotine that might cause smokers to build a better SN which might be the reason they normally do not get PD. All these effects are strongest in men, some of them not seen in women. Green tea extract, grape seed extract, B-complex, and zinc need to be taken with this food since they each easily cause severe nausea, especially at the 2 or 3 pill levels I take of the extracts (but not zinc). Black tea extract does not cause the nausea. I take coffee before exercise (3 tablespoons in 16 oz) and black tea (2 bags Earl Grey in 16 oz) after exercise with the meal.
I wonder if the reason sleep is a problem is because the brain is suffering from lack of oxygen during the night and symptoms force us to wake up. All symptoms seem worse when waking up, but hyperventilating seems to help a little, not to mention water (or rather, the coffee).
Saturday, February 28, 2015
curcumin and piperine, post to PD forum
Megacognito mentioned Longvida(R) form of curcumin helping and he said it had a study to back it up. I have been interested in curcumin because it is unique and therefore may have the possibility of helping in ways that are different from other methods, and therefore more likely to be additive in benefit. The problem is that curcumin is not bioavailable and has not been shown to help in the human brain in any condition at any dose. Many companies and people have been searching for ways around this, further indicating there is a consensus that it would be great if you can get it in the human brain. It appears C3 and Longvida are the main ones that the supplement industry has adopted and the best.
So I looked up the abstract, checked the article-publishing history of the authors (looked good, no conflict of interests except Longvida paid for the study), and I paid the $36 to get the pdf. The only potential drawback is that all 3 researchers are at Australia's Swinburn University. The Longvida company is in Indiana. The product is being incorporated in mainstream supplement lines (NOW foods being the cheaper one with Longvida), available anywhere like amazon, vitacost, and iherb. The trial was properly registered in Australia as ACTRN12612001027808 so you can see the study design in detail. The abstract is www.ncbi.nlm.nih.gov/pubmed...
Working memory and sustained attention were the things helped the most. Participants did NOT have dementia or Parkinsons. This was a study on healthy adults. Its mechanism of action may be merely another MAO-I that can increase dopamine, but for several reasons this natural method may be better than pharmaceuticals.
The reviews at Amazon are worth reading:
www.amazon.com/Curcumin-Lon...
But the NOW foods brand is cheaper.
But is this better than the older and more popular C3 curcumin when used with Bioperine? Bioperine is a popular brand of concentrated black pepper curcumin and other supplements include in their pills. It enables curcumin to remain in an active form in the blood.
A C3 curcumin study in AD patients did not show a benefit, but it did not use Bioperine to greatly (20x) amplify the curcumin and it was only 18 AD subjects that were treated. There has been more hope for curcumin in AD than PD.
www.ncbi.nlm.nih.gov/pubmed...
But generally curcumin has been receiving positive results in inflammation and arthritis.
This C3 study included bioavailability data and comparing this to a paper for longvida www.ncbi.nlm.nih.gov/pubmed...
I get that longvida free curcumin in the blood was 17 times better per mg dose. However, I can't tell if the mg dose in this 2nd paper was "as Curcumin" or "as longvida". If it was as Longvida, then the bioavailability was 85 times better than C3 of the Curcumin that was absorbed. I believe it is 85x better on a curcumin basis, not counting the effect of Bioperine (95% piperine) in either.
The least expensive brand with Longvida is $0.50 per pill containing 80 mg while the least expensive C3 brand (swanson or now) is $0.25 per pill containing 825 mg, so you get 20 times more per dollar for the C3 products. Also, they are not necessarily larger pills because the Longvida is 80% additives that help in absorption, but C3 can be 95% curcumin. The C3 products also often contain peperine which greatly increases curcumin bioavailability (20x more than curcumin alone) but that does not mean equal benefit will be seen with C3 and Longvida because they might be a similar mechanism as piperine for bioavailability. But it seems to be a different mechanism, so it should help with both, but I did not see bioperine mixed with any Longvida products. Five strong dashes of white or black pepper (0.1 g) will provide more piperine than the 2 to 5 mg Bioperine in C3 curcumin capsules.
Tumeric is 3% curcumin according to wiki, and I see you might be able to tolerate 2 to 4 grams turmeric in a ginger-turmeric tea. A website says you should add 3% black pepper to maximize turmeric absorption. This is a 1 to 1 ratio of black pepper to curcumin, whereas only 1% Bioperine (95% piperine from black pepper) to curcumin is needed in C3 pills. Black pepper is about 7% piperine, so 1 to 1 is about 3.5% piperine, so it's an even better ratio than the Bioperine used in pills. There are probably other things in turmeric that help in curcumin absorption, like oils that Longvida depends on, so it's possible turmeric is as good as Longvida needing only 7 times more (since turmeric is 3% curcumin and Longvida is 20% curcumin). C3 also seems like it is trying to copy what the inventors think are good in turmeric that helps curcumin absorb, being a complex of curcumins like turmeric instead of a single compound. At only 3% curcumin in tumeric, the absorption from a 3 gram turmeric tea (very strong, 1 teaspoon of turmeric powder) with 5 strong dashes of black pepper will have to absorb 4 times better than C3+bioperine to equal 1 C3 pill. This is definitely possible, and if it absorbs as well as longvida due to its complex mixture of oil, this tea is equal to 1 longvida pill.
It seems Longvida will work better (even on a cost basis) than C3 if you take it with 0.1 g black pepper.
Quercitin, coconut oil, silibirin and heat increase bioavailability:
www.turmericforhealth.com/g...
The amazon reviews for C3 and Longvida are both good, but it would take a lot of work to determine if the reviews really reflect benefit and not placebo. Nutritional supplements generally get excellent reviews.
Piperine reduces depression and improves cognition.
=====
comment on a review at amazon:
Longvida absorbs 85 times better than C3 on a curcumin basis, 7 times better on a cost basis using your data, but therefore 3 times worse than C3+bioperine on a cost basis. Four strong dashes of pepper (75 mg at 7.5% piperine in black pepper can offset this. A problem I have with the bioperine story: the only paper I could find on it was with curcumin, not C3 or Longvida. They used 20 mg piperine and 2 g curcumin, and the full 20 mg might be needed for a "threshold" effect. Even without this, it means they need to use 5 mg Bioperine instead of the typical 2 or 3 mg for 500 mg pills.
I wonder if both C3 and Longvida are merely trying to copy what you see in turmeric, both the oils and complex curcumins. Are the oils in plants nano-mixed with the active ingredients? How does C3's curcumin composition compare to turmeric?
I'm reading that heat and oils helps the active ingredients absorb, so that a hot turmeric tea with 1 teaspoon turmeric powder (7% curcumin+others?) and 0.1 gram black powder should work 20x (2000%) better than Longvida 500 mg pills and 7 times better than C3+bioperine.
Concerning the comparison between bioperine and black pepper, piperine is the "active" pungent ingredient of black pepper, so you can taste the potency. Bioperine is merely an extract, so it can only decrease bioavailability compared to the original spice. I just tasted 3 mg of bioperine from an opened C3 capsule and would say its pungency is equal to or less than 1 dash of black pepper (easily tolerable), indicating the 95% piperines is too high, or the 7% piperines estimate I used above for black pepper is too low, or Wikipedia's comments on the source of pepper pungency are wrong.
To what extent are these nutritional supplements up to the same games the Pharmaceuticals have been playing forever? You mention Bioperine as strongly supported via research, but my taste buds indicate it is not as good as a dash of pepper. Likewise C3 and Longvida are using the expectation of profit to fund research, but are we going to miss out on the obvious alternative of whole, cooked, turmeric from lack of funded research? Where's the turmeric paper that shows how much curcumin was in the blood after a meal using 4 grams of it?
==========
Post to PD forum and Dr Trutt in response to 2 articles by Dr Trutt:
http://truttmd.com/curcumin-caveat-emptor-not-all-brands-are-created-equal/
http://truttmd.com/curcumin-update-theracurmin/
Dr Trutt, the chart you got from youtube is from a Japanese study that was funded by the Japanese Theracumin company. Prior to their measurement of "curcumin", they used "1000 U beta-glucuronidase at 37 C for 1 hr to hydrolyze the curcumin conjugates" which sounds like they did not measure free curcumin. This correlates with your previous comments questioning a previous study's BCM-95's "free curcumin" data, since this study found a lot of "curcumin" in BCM-95. They never mention free curcumin or the conjugates in plasma.
The data are based on curcumin in the pills and BCM-95 has 17 times more per pill, so even Theracumin's paid researchers showing 10x better theracumin absorption are admitting BCM-95 per pill is 70% better. Theracumin is charging 30x more per curcumin, so at 10x better theracumin absorption per curcumin, BCM is still 3x less expensive per effectiveness. So, BCM-95 is 3x less expensive and you can take 3.5 pills instead of 6 to get the same effect.
Again, this does not seem to mean "free curcumin". But there seems to be only 1 study on longvida free curcumin, and I can't get the entire artilce
An indian study looked at their own formulation of 6% curcumin: "lipidic formulation of CRM (CRM-LF). CRM-LF consisted of CRM (6.17% w/w), Gelucire44/14 (16.46% w/w), Labrasol (5.76% w/w), Vitamin E TPGS (3.29% w/w), PEG 400 (55.55% w/w), ethanol (8.23% w/w), anhydrous citric acid (2.88% w/w) and HPMC E5 (1.64% w/w). CRM-LF forms the nanosized globules upon dilution with aqueous medium."
They got 1.3 uM/L free curcumin max when converted to a 2 g dose. They patented it and published in 2012 titled "Bioavailability of a Lipidic Formulation of Curcumin in Healthy Human Volunteers"
They did not have controls, so the complaint you made about BCM-95 might also be made here.
What do you think about people trying to mix turmeric or curcumin in a ultrasonic denture cleaner with heated lecithin to try to get a similar formulation?
So I looked up the abstract, checked the article-publishing history of the authors (looked good, no conflict of interests except Longvida paid for the study), and I paid the $36 to get the pdf. The only potential drawback is that all 3 researchers are at Australia's Swinburn University. The Longvida company is in Indiana. The product is being incorporated in mainstream supplement lines (NOW foods being the cheaper one with Longvida), available anywhere like amazon, vitacost, and iherb. The trial was properly registered in Australia as ACTRN12612001027808 so you can see the study design in detail. The abstract is www.ncbi.nlm.nih.gov/pubmed...
Working memory and sustained attention were the things helped the most. Participants did NOT have dementia or Parkinsons. This was a study on healthy adults. Its mechanism of action may be merely another MAO-I that can increase dopamine, but for several reasons this natural method may be better than pharmaceuticals.
The reviews at Amazon are worth reading:
www.amazon.com/Curcumin-Lon...
But the NOW foods brand is cheaper.
But is this better than the older and more popular C3 curcumin when used with Bioperine? Bioperine is a popular brand of concentrated black pepper curcumin and other supplements include in their pills. It enables curcumin to remain in an active form in the blood.
A C3 curcumin study in AD patients did not show a benefit, but it did not use Bioperine to greatly (20x) amplify the curcumin and it was only 18 AD subjects that were treated. There has been more hope for curcumin in AD than PD.
www.ncbi.nlm.nih.gov/pubmed...
But generally curcumin has been receiving positive results in inflammation and arthritis.
This C3 study included bioavailability data and comparing this to a paper for longvida www.ncbi.nlm.nih.gov/pubmed...
I get that longvida free curcumin in the blood was 17 times better per mg dose. However, I can't tell if the mg dose in this 2nd paper was "as Curcumin" or "as longvida". If it was as Longvida, then the bioavailability was 85 times better than C3 of the Curcumin that was absorbed. I believe it is 85x better on a curcumin basis, not counting the effect of Bioperine (95% piperine) in either.
The least expensive brand with Longvida is $0.50 per pill containing 80 mg while the least expensive C3 brand (swanson or now) is $0.25 per pill containing 825 mg, so you get 20 times more per dollar for the C3 products. Also, they are not necessarily larger pills because the Longvida is 80% additives that help in absorption, but C3 can be 95% curcumin. The C3 products also often contain peperine which greatly increases curcumin bioavailability (20x more than curcumin alone) but that does not mean equal benefit will be seen with C3 and Longvida because they might be a similar mechanism as piperine for bioavailability. But it seems to be a different mechanism, so it should help with both, but I did not see bioperine mixed with any Longvida products. Five strong dashes of white or black pepper (0.1 g) will provide more piperine than the 2 to 5 mg Bioperine in C3 curcumin capsules.
Tumeric is 3% curcumin according to wiki, and I see you might be able to tolerate 2 to 4 grams turmeric in a ginger-turmeric tea. A website says you should add 3% black pepper to maximize turmeric absorption. This is a 1 to 1 ratio of black pepper to curcumin, whereas only 1% Bioperine (95% piperine from black pepper) to curcumin is needed in C3 pills. Black pepper is about 7% piperine, so 1 to 1 is about 3.5% piperine, so it's an even better ratio than the Bioperine used in pills. There are probably other things in turmeric that help in curcumin absorption, like oils that Longvida depends on, so it's possible turmeric is as good as Longvida needing only 7 times more (since turmeric is 3% curcumin and Longvida is 20% curcumin). C3 also seems like it is trying to copy what the inventors think are good in turmeric that helps curcumin absorb, being a complex of curcumins like turmeric instead of a single compound. At only 3% curcumin in tumeric, the absorption from a 3 gram turmeric tea (very strong, 1 teaspoon of turmeric powder) with 5 strong dashes of black pepper will have to absorb 4 times better than C3+bioperine to equal 1 C3 pill. This is definitely possible, and if it absorbs as well as longvida due to its complex mixture of oil, this tea is equal to 1 longvida pill.
It seems Longvida will work better (even on a cost basis) than C3 if you take it with 0.1 g black pepper.
Quercitin, coconut oil, silibirin and heat increase bioavailability:
www.turmericforhealth.com/g...
The amazon reviews for C3 and Longvida are both good, but it would take a lot of work to determine if the reviews really reflect benefit and not placebo. Nutritional supplements generally get excellent reviews.
Piperine reduces depression and improves cognition.
=====
comment on a review at amazon:
Longvida absorbs 85 times better than C3 on a curcumin basis, 7 times better on a cost basis using your data, but therefore 3 times worse than C3+bioperine on a cost basis. Four strong dashes of pepper (75 mg at 7.5% piperine in black pepper can offset this. A problem I have with the bioperine story: the only paper I could find on it was with curcumin, not C3 or Longvida. They used 20 mg piperine and 2 g curcumin, and the full 20 mg might be needed for a "threshold" effect. Even without this, it means they need to use 5 mg Bioperine instead of the typical 2 or 3 mg for 500 mg pills.
I wonder if both C3 and Longvida are merely trying to copy what you see in turmeric, both the oils and complex curcumins. Are the oils in plants nano-mixed with the active ingredients? How does C3's curcumin composition compare to turmeric?
I'm reading that heat and oils helps the active ingredients absorb, so that a hot turmeric tea with 1 teaspoon turmeric powder (7% curcumin+others?) and 0.1 gram black powder should work 20x (2000%) better than Longvida 500 mg pills and 7 times better than C3+bioperine.
Concerning the comparison between bioperine and black pepper, piperine is the "active" pungent ingredient of black pepper, so you can taste the potency. Bioperine is merely an extract, so it can only decrease bioavailability compared to the original spice. I just tasted 3 mg of bioperine from an opened C3 capsule and would say its pungency is equal to or less than 1 dash of black pepper (easily tolerable), indicating the 95% piperines is too high, or the 7% piperines estimate I used above for black pepper is too low, or Wikipedia's comments on the source of pepper pungency are wrong.
To what extent are these nutritional supplements up to the same games the Pharmaceuticals have been playing forever? You mention Bioperine as strongly supported via research, but my taste buds indicate it is not as good as a dash of pepper. Likewise C3 and Longvida are using the expectation of profit to fund research, but are we going to miss out on the obvious alternative of whole, cooked, turmeric from lack of funded research? Where's the turmeric paper that shows how much curcumin was in the blood after a meal using 4 grams of it?
==========
Post to PD forum and Dr Trutt in response to 2 articles by Dr Trutt:
http://truttmd.com/curcumin-caveat-emptor-not-all-brands-are-created-equal/
http://truttmd.com/curcumin-update-theracurmin/
Dr Trutt, the chart you got from youtube is from a Japanese study that was funded by the Japanese Theracumin company. Prior to their measurement of "curcumin", they used "1000 U beta-glucuronidase at 37 C for 1 hr to hydrolyze the curcumin conjugates" which sounds like they did not measure free curcumin. This correlates with your previous comments questioning a previous study's BCM-95's "free curcumin" data, since this study found a lot of "curcumin" in BCM-95. They never mention free curcumin or the conjugates in plasma.
The data are based on curcumin in the pills and BCM-95 has 17 times more per pill, so even Theracumin's paid researchers showing 10x better theracumin absorption are admitting BCM-95 per pill is 70% better. Theracumin is charging 30x more per curcumin, so at 10x better theracumin absorption per curcumin, BCM is still 3x less expensive per effectiveness. So, BCM-95 is 3x less expensive and you can take 3.5 pills instead of 6 to get the same effect.
Again, this does not seem to mean "free curcumin". But there seems to be only 1 study on longvida free curcumin, and I can't get the entire artilce
An indian study looked at their own formulation of 6% curcumin: "lipidic formulation of CRM (CRM-LF). CRM-LF consisted of CRM (6.17% w/w), Gelucire44/14 (16.46% w/w), Labrasol (5.76% w/w), Vitamin E TPGS (3.29% w/w), PEG 400 (55.55% w/w), ethanol (8.23% w/w), anhydrous citric acid (2.88% w/w) and HPMC E5 (1.64% w/w). CRM-LF forms the nanosized globules upon dilution with aqueous medium."
They got 1.3 uM/L free curcumin max when converted to a 2 g dose. They patented it and published in 2012 titled "Bioavailability of a Lipidic Formulation of Curcumin in Healthy Human Volunteers"
They did not have controls, so the complaint you made about BCM-95 might also be made here.
What do you think about people trying to mix turmeric or curcumin in a ultrasonic denture cleaner with heated lecithin to try to get a similar formulation?
Monday, February 23, 2015
parkinson's and metals
1995 ferritin not increased in SN, but iron and iron export protein were. http://www.ncbi.nlm.nih.gov/pubmed/24113558
1991 However, only in PD was there an increased total iron level, decreased ferritin content, decreased copper content, and an increased zinc concentration in substantia nigra. PD has generalized reduction in brain ferritin immunoreactivity even in SN http://www.ncbi.nlm.nih.gov/pubmed/1832073
2012 Pakistan, N=50 The current study showed that generally there is no significant difference between the patients with the idiopathic Parkinson disease and healthy controls in terms of serum iron and ferritin levels. http://www.ncbi.nlm.nih.gov/pubmed/24261127
2013 These results implicate a neuroprotective role of mitochondrial ferritin (FtMt) in neurodegenerative diseases. http://www.ncbi.nlm.nih.gov/pubmed/23916831
2014 review free article It is also found that, by maintaining mitochondrial iron homeostasis, FtMt could prevent 6-hydroxydopamine induced dopaminergic cell damage in Parkinson's disease. It protects mitochondria from iron-induced oxidative damage presumably through sequestration of potentially harmful excess free iron. Its expression in increased in PD, showing defensive action is being taken. http://www.ncbi.nlm.nih.gov/pubmed/24596558
2011 japan N=249 Higher intake of iron, magnesium, and zinc was independently associated with a reduced risk of PD. Copper and manganese not correlated. http://www.ncbi.nlm.nih.gov/pubmed/21497832
1991 However, only in PD was there an increased total iron level, decreased ferritin content, decreased copper content, and an increased zinc concentration in substantia nigra. PD has generalized reduction in brain ferritin immunoreactivity even in SN http://www.ncbi.nlm.nih.gov/pubmed/1832073
2012 Pakistan, N=50 The current study showed that generally there is no significant difference between the patients with the idiopathic Parkinson disease and healthy controls in terms of serum iron and ferritin levels. http://www.ncbi.nlm.nih.gov/pubmed/24261127
2013 These results implicate a neuroprotective role of mitochondrial ferritin (FtMt) in neurodegenerative diseases. http://www.ncbi.nlm.nih.gov/pubmed/23916831
2014 review free article It is also found that, by maintaining mitochondrial iron homeostasis, FtMt could prevent 6-hydroxydopamine induced dopaminergic cell damage in Parkinson's disease. It protects mitochondria from iron-induced oxidative damage presumably through sequestration of potentially harmful excess free iron. Its expression in increased in PD, showing defensive action is being taken. http://www.ncbi.nlm.nih.gov/pubmed/24596558
2011 japan N=249 Higher intake of iron, magnesium, and zinc was independently associated with a reduced risk of PD. Copper and manganese not correlated. http://www.ncbi.nlm.nih.gov/pubmed/21497832
Wednesday, February 18, 2015
parkinson's diet
I'll edit this as I learn more.
I've been researching how to delay/slow Parkinson's with diet/nutrition. These are proven by many epidemiological studies and/or in animals, but my list is restricted to compounds that are also known to cross the blood-brain barrier in humans. I now have a twitch in my left thumb and index finger if I put them in the right position. Here's the ideal diet:
1 to 3 packs of cigarettes worth of nicotine per day
3+ cups of green tea (2+ pills of the extract)
raw broccoli twice a day
3+ cups of black tea (2+ pills of the extract)
2 beers w/ 3 tablespoons brewer's yeast or can of sardines to raise uric acid to gout-danger levels
coconut oil to provide brain energy by ketones since the glucose energy path has been compromised
3 egg yolks or equivalent shrimp to raise cholesterol in diet. Low cholesterol causes damage.
1200 IU vitamin E
2000 IU vitamin D
fish oil (heavy on omega-3's)nn
3+ cups of coffee (or caffeine pills)
No milk products
selenocysteine (need to investigate)
zinc.
Many of these are (not by coincidence) free-iron chelators in the brain (nicotine, caffeine, tea extracts, uric acid, and possibly omega-3s), regardless of whatever other benefit they provide.
Ideally, the beer and yeast are split to 2 or 3 times a day with lactic-acid generating exercise which blocks uric acid excretion. Exercise also lessons danger to neurons that are in the process of trying to die by increasing oxygen levels in the brain.
Also, limit intellectual activities and try to work outside. (high school educated outdoor workers get it at least 10 years later than others). Also, sleep as good as possible and no mind/emotion stressors.
There is a laundry-list of things that placed me in the higher-risk category (male, intellectual, 1970's pesticide exposure in youth (4x to 10x risk increase), non-smoker (4x risk), severe elemental mercury vapor exposure at age 11, milk, history of very low vitamin D) but for several reason's my high-dose vitamin C "exposure" (10 grams/day for for 10 years) increasing free-copper (if not free-iron) is my best guess.
I've been researching how to delay/slow Parkinson's with diet/nutrition. These are proven by many epidemiological studies and/or in animals, but my list is restricted to compounds that are also known to cross the blood-brain barrier in humans. I now have a twitch in my left thumb and index finger if I put them in the right position. Here's the ideal diet:
1 to 3 packs of cigarettes worth of nicotine per day
3+ cups of green tea (2+ pills of the extract)
raw broccoli twice a day
3+ cups of black tea (2+ pills of the extract)
2 beers w/ 3 tablespoons brewer's yeast or can of sardines to raise uric acid to gout-danger levels
coconut oil to provide brain energy by ketones since the glucose energy path has been compromised
3 egg yolks or equivalent shrimp to raise cholesterol in diet. Low cholesterol causes damage.
1200 IU vitamin E
2000 IU vitamin D
fish oil (heavy on omega-3's)nn
3+ cups of coffee (or caffeine pills)
No milk products
selenocysteine (need to investigate)
zinc.
Many of these are (not by coincidence) free-iron chelators in the brain (nicotine, caffeine, tea extracts, uric acid, and possibly omega-3s), regardless of whatever other benefit they provide.
Ideally, the beer and yeast are split to 2 or 3 times a day with lactic-acid generating exercise which blocks uric acid excretion. Exercise also lessons danger to neurons that are in the process of trying to die by increasing oxygen levels in the brain.
Also, limit intellectual activities and try to work outside. (high school educated outdoor workers get it at least 10 years later than others). Also, sleep as good as possible and no mind/emotion stressors.
There is a laundry-list of things that placed me in the higher-risk category (male, intellectual, 1970's pesticide exposure in youth (4x to 10x risk increase), non-smoker (4x risk), severe elemental mercury vapor exposure at age 11, milk, history of very low vitamin D) but for several reason's my high-dose vitamin C "exposure" (10 grams/day for for 10 years) increasing free-copper (if not free-iron) is my best guess.
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