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

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:

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.

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
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:

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:

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.

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

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.

 2013 These results implicate a neuroprotective role of mitochondrial ferritin (FtMt) in neurodegenerative diseases.

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.

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.

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)

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.

Tuesday, February 10, 2015

vitamin C, libido, and parkinson's

I took 12 grams vitamin C for much of about 10 years from age 27 to 37. Myself and the only two others I knew of who took more than 10 grams a day for more than a week or two noticed a large decrease in libido. I took so much because it greatly relieved stress. I stopped because I got married. Fast-forward 10 more years and at age 47 I seem to have Parkinson's. Then I remembered Dr Pauling's videos from about 1981 and on seem to show him displaying two symptoms of Parkinsons: weak voice, trembling hands, and head nodding just a tad more than you would expect. After some researching, I see that more than 2 grams a day causes copper to shift from the protein-bound state to free copper, and that the protein-bound state is needed to protect the part of the brain that is damaged in Parkinson's. The protein-bound state is needed to protect the brain from iron toxicity. If not, then the iron damages dopamine producing cells, which is directly related to libido. As a side note, my own research into how much vitamin C animals produce (and primates and guinea pigs need) would convert to 0.5 to 2 grams a day for a human. The biggest error in saying 10 grams a day is that it is based on body weight, but body weight is not the correct measure in converting nutrition and toxicity, but caloric intake is, which is lower for larger animals. Keep in mind, I've read all of Pauling, Hoffer, Cathcart, Cameron, and Stone's work on VitC and you can't find anyone these days who is as big a proponent as I was.

1500 mg/day decreases protein-bound copper "Serum ceruloplasmin activity was significantly reduced (p less than 0.01) at every data point throughout the ascorbic acid supplementation period."
1000 mg/day decreased:
Effect not seen in guinea pigs and men
Also reduced in guinea pigs:
Also in rats:
Ceruloplasmin was not reduced at 605 mg/day in men, but its activity was
Magnesium was lowered in guinea pigs, but not ceruloplasmin
vitamin c in blood correlates with lower ceruloplasmin in humans
Small effect seen in monkeys on marginal copper diet

Low ceruloplasmin including from mutations is strongly implicated in PD and AD:
Low ceruloplasmin correlate with younger-onset PD
Mutations for low ceruloplasmin allow iron oxidation

Linus pauling institute:
Vitamin C
Although vitamin C supplements have produced copper deficiency in guinea pigs (17), the effect of vitamin C supplements on copper nutritional status in humans is less clear. Two small studies in healthy, young adult men indicate that the oxidase activity of ceruloplasmin may be impaired by relatively high doses of supplemental vitamin C. In one study, vitamin C supplementation of 1,500 mg/day for two months resulted in a significant decline in ceruloplasmin oxidase activity (18). In the other study, supplements of 605 mg/day of vitamin C for three weeks resulted in decreased ceruloplasmin oxidase activity, although copper absorption did not decline (19). Neither of these studies found vitamin C supplementation to adversely affect copper nutritional status.