TG

Neurosci Lett. 2002 Apr 5;322(2):75-8. Related Articles, Links

Beta-amyloid deposition in the brains of rats chronically infused with thiorphan or lipopolysaccharide: the role of ascorbic acid in the vehicle.

Hauss-Wegrzyniak B, Wenk GL.

Arizona Research Laboratories, Division of Neural Systems, Memory & Aging, University of Arizona, Tucson, AZ 85724, USA.

Beta-amyloid deposition and neuroinflammation are two important features of Alzheimer's disease (AD) that may influence its progression. Chronic infusion of lipopolysaccharide (LPS) into the rodent 4th ventricle reproduces many of the neurobiological changes seen in AD. Chronic infusion of ascorbic acid containing thiorphan, an inhibitor of the enzyme neprilysin that catabolizes beta-amyloid, into the hippocampus induces extracellular deposition of beta-amyloid fibrils. We investigated whether the combined presence of chronic neuroinflammation could exacerbate the deposition of beta-amyloid induced by thiorphan. The infusion of any solution containing ascorbic acid alone or with thiorphan or LPS increased the level of intraneuronal beta-amyloid immunoreactivity. Solutions that did not contain ascorbic acid were not associated with increased intraneuronal beta-amyloid immunoreactivity. The role of neprilysin in the deposition of beta-amyloid in AD brains remains undetermined.

Nucleic Acids Res. 1989 January 25; 17(2): 517-522.

 

Thanks for the information.

What would you consider a high dose of vitamin C? I am on the salt/C protocol and am ramping up to 6 grams of each per day. Right now I am at 2 grams and will increase by one gram per month.

It does make me herx and a lot of people swear by it to help get rid of lyme symptoms.

Would there be a safe substitute for the vitamin C to support the immunune system?

I do not have dementia nor do I have the cognitive memory type problems or brain fog that some people with lyme experience.

Hiker53

[This message has been edited by hiker53 (edited 30 August 2005).]
 

Tom,
Thanks for the article!
 

i do genuflect, and prostrate my self in

deepest rodentine gratitude, and deference

to my murine brethren who,due to a paucity

of PETA volunteers, doth toil there

for us for a lifetime on that ferris wheel

in the box for helping to impart this knowledge to

us before entering the hereafter with all

the rights and priveleges appertaining

thereunto, by way of that gee-o-teen

(lymebrain spell. moment), that is also

sitting on the countertop...

aight!, aight!...what can i say, but that,its 12:30 a.m., and i can't sleep...

[This message has been edited by pq (edited 31 August 2005).]
 

Rossig L, Hoffmann J, Hugel B, et al. Circulation 2001;104:2182-2187.
http://www.findarticles.com/p/articles/mi_m0FDN/is_6_6/ai_81761472

Free Radic Biol Med. 2004 Oct 15;37(8):1282-9.

We conclude that ascorbate may protect arteriolar vasoconstrictor responsiveness in sepsis by inhibiting excessive NO production.

PMID: 15451067

Fruit, Veggie Juices May Cut Alzheimer's Risk
Antioxidants May Be the Key, Say Researchers

The finding was presented in Washington, at the Alzheimer's Association International Conference on Prevention of Dementia.

June 20, 2005

Alzheimer's Disease Brain May Be Able to Heal
Clearing Brain Plaque Lets Mouse Brain Cells Recover

Jan. 20, 2005

The hallmark of Alzheimer's disease is plaque formation in areas of the brain that control memory and thinking skills. While the cause of Alzheimer's disease remains unknown, the researchers say that evidence indicates that plaque formation and accumulation may play a role.

In a recent experiment, scientists succeeded in deleting plaque in mice with a disease similar to Alzheimer's. The mice's brain cells also bounced back, to some extent, from plaque damage.

SOURCES: Brendza, R. The Journal of Clinical Investigation, online edition.

News release, Washington University School of Medicine.

Alzheimer's disease has been associated with a deficit of the neurotransmitter, acetylcholine, in the brain (10)
http://lpi.oregonstate.edu/infocenter/othernuts/choline/

A central factor in Alzheimer's disease is ApolipoProteinE, which is produced by glial cells and accounts for at least 50% of the Alzheimer's disease that occurs between 60 - 80 years of age.

APOE plays a central role in cerebral cholesterol transport. Recent evidence has shown that cholesterol metabolism is involved in neuroplasticity.

Epidemiological studies are now implicating cholesterol metabolism in Alzheimer causation.

Recent evidence supports the hypothesis that acetylcholine, a fundamental neurotransmitter in neuroplasticity, inhibits both senile plaque and neurofibrillary tangle formation (see figure adapted from Fisher, 2000).

This hypothesis suggests that drugs which increase acetylcholine function, such as cholinesterase inhibitors, may slow or stop Alzheimer progression.
http://www.alzforum.org/res/for/journal/ashford/default.asp

Gene study suggests vitamin E helps blocks Alzheimer's

04/05/2005- Scientists have found genetic proof that vitamin E can help protect against Alzheimer's disease, said DSM yesterday.

This most recent study was published in Nutritional Neuroscience (February 2005, 8;21-29).

Increased TNF alpha and angiotensin damage the endothelial cells that line the blood vessels and lymph vessels.

Eventually monocytes accumulate lipids and become foam cells which eventually form the fatty streaks of atherosclerosis.

IMPORTANT:
DISCOVERY SHOWS NEW VITAMIN C HEALTH BENEFITS
12-13-04

By David Stauth, 541-737-0787
SOURCES: Fred Stevens, 541-737-9534
Balz Frei, 541-737-5078
CORVALLIS -

Researchers in the Linus Pauling Institute at Oregon State University have made a major discovery about the way vitamin C functions in the human body - a breakthrough that may help explain its possible value in preventing cancer and heart disease.

The study, which explores the role of vitamin C in dealing with the toxins that result from fat metabolism, was just published in a professional journal, Proceedings of the National Academy of Sciences.

It contradicts the conclusions of some research that was widely publicized three years ago, which had suggested that this essential nutrient might actually have toxic effects.

The new OSU study confirmed some of the results of that earlier laboratory study, which had found vitamin C to be involved in the formation of compounds potentially damaging to DNA. But that research, scientists say, only provided part of the story about what actually happens in the human body.

The newest findings explain for the first time how vitamin C can react with and neutralize the toxic byproducts of human fat metabolism.

"This is a previously unrecognized function for vitamin C in the human body," said Fred Stevens, an assistant professor in the Linus Pauling Institute. "We knew that vitamin C is an antioxidant that can help neutralize free radicals.

But the new discovery indicates it has a complex protective role against toxic compounds formed from oxidized lipids, preventing the genetic damage or inflammation they can cause."

Some earlier studies done in another laboratory had exposed oxidized lipids - which essentially are rancid fats - to vitamin C, and found some reaction products that can cause DNA damage.

These test tube studies suggested that vitamin C could actually form "genotoxins" that damage genes and DNA, the types of biological mutations that can precede cancer.

But that study, while valid, does not tell the whole story, the OSU researchers say.

"It's true that vitamin C does react with oxidized lipids to form potential genotoxins," said Balz Frei, professor and director of the Linus Pauling Institute, and co-author on this study.

"But the process does not stop there. We found in human studies that the remaining vitamin C in the body continues to react with these toxins to form conjugates - different types of molecules with a covalent bond - that appear to be harmless."

In human tests, the OSU scientists found in blood plasma extraordinarily high levels of these conjugates, which show this protective effect of vitamin C against toxic lipids.

"Prior to this, we never knew what indicators to look for that would demonstrate the protective role of vitamin C against oxidized lipids," Stevens said. "Now that we see them, it becomes very clear how vitamin C can provide a protective role against these oxidized lipids and the toxins derived from them.

And this isn't just test tube chemistry, this is the way our bodies work.
"This discovery of a new class of lipid metabolites could be very important in our understanding of this vitamin and the metabolic role it plays," Stevens said.

"This appears to be a major pathway by which the body can get rid of the toxic byproducts of fat metabolism, and it clearly could relate to cancer prevention."

Oxidation of lipids has been the focus of considerable research in recent years, the scientists say, not just for the role it may play in cancer but also in other chronic diseases such as heart disease, Alzheimer's disease, and autoimmune disorders.

The toxic products produced by fat oxidation may not only be relevant to genetic damage and cancer, researchers believe, but are also very reactive compounds that damage proteins.

For instance, there's a protein in LDL, the "bad" cholesterol in your blood, which if damaged by toxic lipids can increase the chance of atherosclerotic lesions.

In continuing research, the OSU team plans to study the role of this newly understood reaction between vitamin C and toxic lipids in atherosclerosis. In clinical studies they plan to examine the blood chemistry of patients who have been diagnosed with coronary artery disease, compared to a healthy control group.

"In the early stages of atherosclerosis, it appears that some of these toxic lipids make white blood cells stick to the arterial wall, and start an inflammatory process that ultimately can lead to heart disease or stroke," Frei said.

"When we better understand that process and the role that micronutrients such as vitamin C play in it, there may be strategies we can suggest to prevent this from happening."

The new findings, the OSU scientists say, also point to new biomarkers that can be useful in identifying oxidative stress in the human body. They may provide an indicator of people who may be at special risk of chronic disease.

Last Update:Tuesday, 14-Dec-2004 11:43:44 PST

For comments or feedback about this site contact [email protected].

Bb uses acetyl CoA (cholesterol and acetylcholine implicated) and is PFK dependent. It is following the glycolysis AND cholesterol pathways. We need to Inhibit these pathways simultaneously.

We know now (recent pubmed abstract) that in lyme disease, vitamins A and E drop. The former to protect our eyes esp. and the latter to protect the brain cells.

It is important to recognize the COMBINATION of things ...Mg pyrophosphate with sublingual B6 or Na + Vitamin C.

We get into a mess when we look at one thing and try to take it apart...determine what is the most beneficial/harmful ingredient. Example: garlic. Is it selenium or sulfur that is most beneficial or is it the COMBINATION?

It's the combination. Watch the pH very, very closely.

All the gram neg. pathogens are missing acids...

 

6 months before Tom's essay appeared in one or more now defunct lymenewsletters( Spot Light On Lyme?) implicating these nutrients, i made a one-to-one connection between the vit. C and my increasing confusion.

i made a similar experiental observation with p-5-p(a form of vit.B6) when taken alone, in the form of neuropathy(numbness and tingling),and when taking a liquid B-complex.

with the vitamin C, it took me 1 to 3 months at best to quit the vit. C, and when i did, i gradually returned to a less severe state; the same with Bcomplex, but it took slightly longer to come to this conclusion.

Before the tick bite(photographic proof of satellite rash(after tick-snap), and wb+ by cdc stnds., i took the same low to moderately high but safe doses of the B complex vits., sometimes megadoses of vit. C, orally taken,and i did not experience the resultant confusion, inexplicable irritability, rage(?), verbal tirades and myriad other neurological, and cognitive manifestations of an increased production of quinolinic acid caused by the above mentioned nutrients.

After infection, i experienced these pardoxical effects.

twice having done i.v. vit. C, but in conjucntion with other antioxidants, and other nutrients including the B complex immediately after a session of i.v. hyd. peroxide, i did NOT experience the confusion, and other negative neuro-cog.effect that the foregoing nutrients induced.

abx ther. prior to having done the i.v. C may have had a lot to do with my NOT experiencing these paradoxical effect of the vit. C and/or B vits.,; or, theoretically, perhaps it was the route--i.v. C vs. oral intake--that explains the lack of the paradoxically negative effect fo the vit. C and aformentioned B vits., because the oral route would involve the transformation of the vit. C many times en route from the digestive system to the liver to the blood; hence tissues and cells...that eventuated in adverse neuro-cognitive manifestations. i'd conjecture that the i.v. C may bypass some physiological step that resulted in the increased quinolinic acid
by brain macrophages. i don't know. this is rank speculation by a 'paperback,' Barnes& Noble__________(fill in the blank).

i was able to very signifcantly quell this effect with niacin and magnesium, nutrients to which Tom also referred in at least one to the 2-3 essays in the newsletter mentioned above.

niacin and magnesium serve the function to temporarily quinolinic acid production by macrophages. antecdotally,i can attest to this function, having to do with N-methyl-d-aspartate receptors.

niacin, in large doses is a multi-edged razor, affecting the heart and liver in terms of inflammation.

the above nutrients induce brain, and, perhaps other macrophages to pump out increased quantities of quinolinic acid that, in turn manifests neurologically, cognitively, and otherwise. i have yet to see a list of the Sx produced by quinolinc acid; if anyone has one, please post it here.

i've seen apparently inexplicable irritability induced by 100,000 mg of vit. C in an internationally known Ph.D-nutritonist,running-walking-medalist whom everyone would objectively say,'they walk the talk'.

years later, when researching lyme, i realized the reason for the apparent inexplicable irritability uncharacteristically but slightly out of proportion to the apparent 'transgression.'

increased level of vit.-C induced quinolinic acid.
its infinitely remote that this person had/has lyme, or other TBDs, and if they did, they'd know the cause almost instantly, and would've wiped out TBDs in short order form prompt and appropriate treatment(s).

i'm still for taking the above nutrients, but i really don't know the parameters underwhich they would be safe to take, and the safest route to take them in moderate to megadoses.

[This message has been edited by pq (edited 31 August 2005).]

[This message has been edited by pq (edited 31 August 2005).]