Wonders of Alpha Lipoic Acid

[Justforfun000]

Not sure if this would be the right forum, but I guess it falls under "science".

I had just emailed my folks a fairly extensive interpretation of a product that seems to be very well researched and consequently worth supplementing with.

Just thought people here might want to have a look and see if they might be interested in checking it out.

I'll reproduce the essence of my email and give the link it came from.

(hmmm...Now I'm having trouble finding the exact link that I reproduced the info below on, but here's another from the same company. This Canadian company is extremely reputable and they back up their science with good references as you can see at the bottom of the page of the link):

http://www.aor.ca/int/related_research/semc.php

I know I keep harping on this one, but try to read through this technical shit thoroughly and understand it.

Of course the vitamins/minerals and Omega 3’s are a given for both of you and especially mom since Dilantin depletes you of a lot of them, but after those basic building blocks, this particular supplement is probably the best overall antioxidant and anti-aging one imaginable. As you can read below, it also prevents and treats a GREAT deal of diseases.

Just to sum up the main points:

1) This particular form of Alpha Lipoic Acid is massively superior to other forms because it is only the + form of this substance which as it explains below is far more effective then the normal one that contains both the + and – forms. You don’t really need to understand this, but it’s very important.
2) Normally this Lipoic acid only has a 22 minutes half life in the body and it’s completely gone in under 3 hours. This formulation is the only one that has sustained release which means it is effective over an 8 to 10 hour period. Again, this is MASSIVELY superior to any other Lipoic Acid product.
3) The protective effect of this nutrient protection helps in cases of diabetes, diabetic neuropathy, mitochondrial dysfunction (cellular damage), liver disease, lactic acidosis and could even help control the replication of the human immunodeficiency virus.
4) It actually recycles other vitamins and detoxifying chemicals in the body. Specifically vitamin C, vitamin E, glutathione and ubiquinone (vitamin q10).
5) One major reason we age is cellular damage caused by oxidative stress. In layman’s terms, oxygen although keeping us alive, releases free radicals which break down cells. Antioxidants mop up these free radicals and protect us from the damage. Lipoic acid in studies shows a MAJOR antioxidant protective effect and it’s the ONLY antioxidant that is both water soluble and fat soluble. Other antioxidants like vitamin E or C for example, are just one or the other.
6) It’s an effective treatment for diabetes and related nerve damage caused by it (diabetic neuropathy). This also would prevent someone from developing diabetes which is becoming much more common these days. Too much alcohol and poor eating habits can cause anyone to develop it.
7) It shows strong evidence of neuroprotective qualities. In other words, any kind of nerve disorders which could include my Tourette’s and Mom’s Trigeminal Neuralgia. Specific diseases it’s already shown evidence for are Parkinson’s, Alzheimer’s, Huntington’s, and amyotrophic lateral sclerosis.
It has shown immune boosting properties. It’s demonstrated improved antibody production in animals.
9) The liver detoxifies the body mainly by using a specific chemical called Glutathione. When we age, it drops dramatically and we can’t detoxify the body like we used to. Vitamin C and other antioxidants help increase it a bit, but Alpha Lipoic Acid has shown amazing results in dramatically increasing it. In older individuals, drops in glutathione levels reached 58% in the heart and 66% in the brain in comparison to younger counterparts. Lipoic acid supplementation increased glutathione levels in the aging brain.
10) In another experiment, liver cells isolated from young and older rats were used to see the effectiveness of alpha Lipoic acid at preventing liver injury. Total glutathione cellular levels were 37.7% lower in older rats. (R+)-Lipoic acid significantly protected the Liver cells against Butylhydroperoxide (an oxidative stress inducing agent) both in the test tube and in the body. The results suggest that ALA is indicated in liver conditions such as alcoholic liver disease and viral hepatitis. ALA was also shown to protect against a liver damaging chemical in animals
11) As we age, our sensitivity to insulin declines and even in normal people (without diabetes), this still means we don’t process energy as effectively. Lipoic Acid increased cellular glucose uptake in a manner similar to insulin. This means it helps our cells naturally metabolize energy in a manner similar to our most efficient time when we were at our prime age in life.
12) It’s been shown to prevent the formation of cataracts
13) It also can treat glaucoma (the gradual aging of the eye that damages the optic nerve and can lead to blindness), and improve eyesight.
14) It shows evidence of preventing Atherosclerosis. (hardening and narrowing of the arteries)
15) Various animal studies have suggested that Lipoic acid can prevent or reduce cell and tissue damage in heart attacks and stroke

That’s the basic summation right there. More detail is below. So can you see why this one is so important? They have it over near me for $50 a bottle. I’m only taking one a day instead of the three a day they suggest for “24 hour protection”. I doubt you’d need it the entire 24 hours. I think one a day covering your waking hours when you’re eating and drinking (especially alcohol) will be enough to give major benefits. So that way one bottle will last you three months. Makes it much more economical.

I still want you both on the AGE Amadori one too from AOR. Same company. Also a major basic anti-aging supplement that covers a lot of basics, but I believe this one is still the most important, so get this one first. If you’re going to take ANY supplements, Make it these three:

1) Omega 3’s
2) Vitamins and minerals
(and yes mom, you need those separate ones because you simply won’t get enough in one tablet. Especially in your case because you are naturally being depleted more then the aveage person thanks to the Dilantin)
3) This Alpha Lipoic Acid (r(+)SR)

I’ll put together the AGE Amadori one eventually and explain why that one is good too. I’ll dumb it down so you’ll understand it more.


R (+) SR - Related Research

Label Info | Related Research | Magazine Article(s) | Related Abstract(s) | FAQ

Alpha lipoic acid (ALA) is an extraordinary antioxidant. Unfortunately, its effectiveness has been limited on two fronts. Firstly, supplemental lipoic acid has been manufactured with the R+ and S- enantiomers – two molecules with the same chemical formula but with different structures. The R+ form is naturally occurring and the beneficial effects of alpha lipoic acid come from the R+ isomer. The S+ form however is artificial, a byproduct of the manufacturing process and is harmful because it is thought to prevent the utilization of the R+ enantiomer. This is especially detrimental with ALA because the molecule has a
very short half-life in the body, estimated at 22 minutes; the second shortcoming of this molecule. The solution is, in theory, simple. To reap the full benefits of Alpha Lipoic Acid, an R+ sustained release formula would be ideal and would offer continual resistance against free radicals and prolonged insulin sensitivity in diabetics.


Pharmacokinetics

ALA is absorbed in the small intestine, carried to the liver via the portal circulation and distributed throughout the body by the systemic circulation. ALA is a small molecule that is readily assimilated in a non-saturable fashion in doses of 50 to 600 mg. It is naturally present in food although in very small quantities. Supplemental ALA reaches doses that are hundreds of times higher than what is found in food. ALA was thought to be a vitamin in humans and animals but it has since been shown that it is endogenously produced. The R+ form of ALA is more active and more absorbable. ALA can cross the blood brain barrier and, after its absorption, it is found intramitochondrially as well as intra and extra cellularly. It therefore prevents oxidative damage both inside and outside our cells and mitochondria throughout the body. The antioxidant effect associated with Lipoic Acid may confer protection in cases of diabetes, diabetic neuropathy, mytochondrial dysfunction, liver disease, lactic acidosis and could even help control the replication of the human immunodeficiency virus.

Alpha lipoic acid and DHLA form a redox couple capable of recycling antioxidants and are involved in cellular energy production. Incredibly, the antioxidant potential of ALA extends to both the reduced and oxidized form of the molecule. Supplementation with Alpha Lipoic acid decreases plasma protein carbonyls, markers of oxidative stress. The molecule recycles important antioxidants such as vitamin C, vitamin E, glutathione and ubiquinone.


Research

There is evidence that lipoic acid is an anti-aging agent. The key to the antiaging effect of ALA lies in its ability to protect the mitochondria from oxidative stress. It has been demonstrated that as we age, our mitochondria’s slowly become less and less efficient at producing energy. This loss of efficiency results in an increased production and release of free radicals, which injure the cell and the mitochondria, leading to a harmful and destructive cycle. In rats however, supplementation with ALA improves mitochondrial function and reduces the production of ROS halting this vicious cycle.

Lipoic acid is a promising treatment for diabetes and its related complications such as diabetic neuropathy, a treatment for which lipoic acid is approved in Germany. ALA improves insulin sensitivity allowing glucose to enter the cell more easily. For ALA to be considered a viable treatment for diabetes, the molecule must confer protection for longer than the 22-minute half-life currently limiting its effectiveness. Sustained release ALA formulations allow for constant improvements in insulin sensitivity and the results obtained in human trials done with sustained release R(+)-lipoic acid are impressive. Supplementation resulted in sustained decreases in blood glucose that averaged 184mg/dl or just over a 46% decrease. A Meta analysis reviewed all the clinical trials undertaken for the treatment of diabetic neuropathy with alpha lipoic acid. 1258 diabetic patients were included in the analysis, the largest study population ever used to evaluate the effectiveness of a particular treatment for diabetic neuropathy. The conclusions favored the use of lipoic acid in this population. The analysis revealed that the molecule is an effective treatment for neuropathies and that oral supplementation for 4-7 months reduces neuropathic deficits and improves cardiac neuropathy. It was also clear that Alpha lipoic acid is a well-tolerated and safe treatment.

• There is some indication that ALA may be helpful for the treatment and prevention of neurodegenerative disorders. Animal studies indicate that ALA may be of benefit for the management and care of Parkinson’s, Alzheimer’s, Huntington’s, and amyotrophic lateral sclerosis.
• It has been suggested that ALA may have immunostimulating properties and was shown to augment antibody production in animals.
• In Alzheimer’s disease, both oxidative stress and energy depletion are thought to play a significant role in the pathological process leading to inflammation, to the generation of advanced glycation end products and the formation of senile plaques eventually leading to nervous tissue damage. Alpha lipoic acid was used in AD with positive results. The molecule counteracts and prevents both oxidation and energy production malfunction.
• In diabetic rats, alpha lipoic acid reduces growth retardation and congenital anomalies in fetuses, supporting the theory that reactive oxygen species are linked to embryonic malformations.
• Animal studies have shown that in a high fructose diet, lipoic acid helps maintain the function of the antioxidant system and lowers lipid peroxidation and insulin resistance.
• Studies in older rats have shown that glutathione levels drop significantly with age. Glutathione is a powerful free radical scavenger and the major antioxidant species found in cells. Drops in glutathione levels in older rats reached 58% in the heart and 66% in the brain in comparison to younger counterparts. Lipoic acid supplementation increased glutathione levels in the aging brain.
• In another experiment, liver cells isolated from young and older rats were used to see the effectiveness of alpha lipoic acid at preventing liver injury. Total glutathione cellular levels were 37.7% lower in older rats. (R+)-lipoic acid significantly protected the hepatocytes against Butylhydroperoxide (an oxidative stress inducing agent) both in vitro and in vivo. The results suggest that ALA is indicated in liver conditions where oxidative stress confers pathology such as alcoholic liver disease and viral hepatitis. ALA was also shown to protect against cadmium-induced hepatotoxicity in animals.
• In vitro, lipoic acid increased cellular glucose uptake in a manner similar to insulin.


Indications

Alpha lipoic acid is indicated for the treatment of any condition where elevated blood glucose levels and free radicals are involved in the disease process. Both of those mechanisms cause problems in several degenerative processes and are both thought to impact the aging process significantly. Alpha lipoic acid can be used to prevent cataract formation, because it can inhibit the enzyme aldose reductase involved in the formation of lens opacities. Supplementation with this antioxidant also improved biochemical parameters in patients suffering from glaucoma and lead to improvements in visual function.

The area that has been studied most intensely when it comes to the use of lipoic acid is its utilization for diabetic patients. Supplementation improves insulin sensitivity, cellular glucose uptake, prevents diabetic complications, prevents protein glycation, reduces plasma free fatty acids, stimulates glycolysis and inhibits aldose reductase. Incredibly, ALA can treat diabetes once it has developed, prevents the progression of complications related to diabetes and alleviates complications if they are already present.

In healthy people, the benefits are not to be overlooked either. Free radicals, which are quenched by (R+)-lipoic acid, are well known for their injurious effect on health. They damage body structures, oxidize lipids, injure blood vessels, can lead to DNA mutations, contribute to inflammation and are thought to play a key role in degenerative disorders. On a different front, elevations in blood glucose levels damage proteins and lipids. Indeed, sugars and their intermediates will attach to amino acid residues and lipids leading to the formation of advanced glycation end products and advanced lipoxidation end products. As we age, insulin sensitivity decreases which contributes to increases in blood glucose levels, which accelerates the glycation/lipoxidation process. This leads to the loss of function in cellular structures and speeds up the aging process. Alpha lipoic acid offsets this course by increasing insulin sensitivity, which enhances glucose uptake by cells and decreases blood sugar levels.

[PainRack]

Just some odd things I picked up

One major reason we age is cellular damage caused by oxidative stress. In layman’s terms, oxygen although keeping us alive, releases free radicals which break down cells. Antioxidants mop up these free radicals and protect us from the damage. Lipoic acid in studies shows a MAJOR antioxidant protective effect and it’s the ONLY antioxidant that is both water soluble and fat soluble. Other antioxidants like vitamin E or C for example, are just one or the other.

This claim should be taken with a bit of salt. The fact is so far, antioxidants don't help improve life expectancy. The science is there but any effect it does have on life expectancy, based on the limited research done so far is too small to be significant.

Unless you're preaching this as a beauty product in which I retract the fishiness of the statement.

[PainRack]

And btw, have you cleared any of the supplements with her regular doctor? She's taking a drug for her pain after all......... The pharmacist should be able to check if they have any interaction with her current meds.

[Justforfun000]

This claim should be taken with a bit of salt. The fact is so far, antioxidants don't help improve life expectancy. The science is there but any effect it does have on life expectancy, based on the limited research done so far is too small to be significant.

Well that's not quite accurate either. They haven't been PROVEN to improve life expectancy, but that doesn't mean they won't. They simply haven't done the studies yet. The theories are sound however.

And btw, have you cleared any of the supplements with her regular doctor? She's taking a drug for her pain after all......... The pharmacist should be able to check if they have any interaction with her current meds.

Dilantin is an anti-convulsant. It's not actually an analgesic. And Alpha Lipoic Acid has no known contraindications other then it can improve blood sugar sensitivity so diabetic people should monitor insulin and sugar levels appropriately.

[mr friendly guy]

Dilantin depletes vitamins? Out of curiosity I looked at MIMS, and the only vitamin it reports to interfere with is vitamin D.

And on an the whole anti-oxidant thing, its not something I am particularly knowledgeable about, but I was under the impression the jury was still out so to speak, despite whatever studies we have performed.

[Justforfun000]

Dilantin depletes vitamins? Out of curiosity I looked at MIMS, and the only vitamin it reports to interfere with is vitamin D.

Another site on the drug said: Long use of phenytoin can decrease the
levels of vitamins D, K, and folic acid in the
body.

I also came across somewhere else claiming it reduced Vitamin E too.

And on an the whole anti-oxidant thing, its not something I am particularly knowledgeable about, but I was under the impression the jury was still out so to speak, despite whatever studies we have performed.

Well the jury is out on actual proof that anti-oxidants will extend life span. It makes SENSE, and they assume it will be borne out in time with studies, but it's a relatively new field of medicine.

[mr friendly guy]

Dilantin depletes vitamins? Out of curiosity I looked at MIMS, and the only vitamin it reports to interfere with is vitamin D.

Another site on the drug said: Long use of phenytoin can decrease the
levels of vitamins D, K, and folic acid in the
body.

I also came across somewhere else claiming it reduced Vitamin E too.
.

I must confess, I haven't heard of that.

Vitamins A, D, E, K are the fat soluble vitamins. Absorption of fat solutble vitamins can become a problem in some people. However I doubt dilantin works by impairing absorption of vitamin D since its kind of synthesised by the body after exposure to UV light.

IIRC besides vitamin D, those other vitamins aren't likely deficient in people from most western countries.

[PainRack]

Well that's not quite accurate either. They haven't been PROVEN to improve life expectancy, but that doesn't mean they won't. They simply haven't done the studies yet. The theories are sound however.

Hence, the "bit" of salt. As I said, the science is there but how significant the effects are are unknown.

Dilantin is an anti-convulsant. It's not actually an analgesic. And Alpha Lipoic Acid has no known contraindications other then it can improve blood sugar sensitivity so diabetic people should monitor insulin and sugar levels appropriately.

I'm sorry, but when I googled Trigeminal Neuralgia and Dilantin, I got pain relief. I'm aware that Dilantin main function was to treat epilepsy but just assumed that it had a secondary effect of treating pain.

[Prozac the Robert]

A good summary of why antioxidants might not be worth bothering with, by Dr Goldacre (medical doctor and writer for the Guardian), from his website.

Ben Goldacre
Saturday June 24, 2006
The Guardian

It can sometimes seem like there are two competing ways to make a decision about any complex matter of evidence based medicine. One is to purchase and digest “How to Read a Paper: The Basics of Evidence-Based Medicine” by Professor Trisha Greenhalgh (BMA Books, a life changing experience if you have a week to spare), and then find, read, and critically appraise every single published academic study independently and in full for yourself. The other more common method is to rely on “experts”, or what I like to call “prejudice”.

But there is a third way: what we might call “Evidence Based Prejudice”. I can’t possibly debunk every single alternative therapy column you will ever read: but if I could show that their single most popular claim has no foundation, then you could safely ignore everything else they say, thus saving valuable brain energy, and freeing up extra time for you to write best-selling novels and eradicate world poverty.

And so to antioxidants. The basic claim of the alternative therapy industry is as follows: free radicals in the body are bad, but antioxidants neutralise free radicals; people who eat vegetables with antioxidants in them live longer, therefore antioxidant tablets are good.

Now this “free-radicals-bad antioxidants-good” morality tale looks great on paper: but if you’re going to read a biochemistry textbook and pull bits out at random, you can prove anything you like. For example, my phagocytic cells build a wall around invading pathogens and then use free radicals – amongst other things - to kill the bacteria off, before the bacteria kill me. They’re probably doing it right now, somewhere in here. So do I need free radical supplements to help me fight infections? Sounds plausible. You can see, now, how I could make some serious money if I ever turned to the dark side (alternative therapists, why not just pick some more chemicals at random from Stryer Biochemistry, 5th Ed.).

Of course the “antioxidants good” story didn’t come entirely out of the blue: it came, like almost all the evidence on diet and health, from observational studies. People who eat well, with plenty of fruit and vegetables in their diet, tend to live longer, healthier lives. But these are observational studies, not intervention studies. These are not studies where you take a few thousand people and make them eat salad. These are surveys, looking at people who already have healthy diets: people like me, and since you’re asking, I also cycle to work, get a good night’s sleep, have a fairly comfortable lifestyle, a stable relationship, and a plausible career. People like me do live longer (thanks for asking) but it’s not just the antioxidants in our rocket salad.

So what happens, then, when people do big studies, forcing people to eat salad? Well it’s not an easy thing to do, if only because it’s difficult to get people to eat what you tell them, and measure what they eat, and check if they’re truthful, and so on: the Multiple Risk Factor Intervention Trial in the 1970s was probably the single biggest medical project ever undertaken, it took 12,866 men, advised them, monitored them, cajoled them, persuaded them, followed them up for a decade, and found little benefit from dietary change. Intervention trials for diet have continued, since then, to produce negative results. Maybe they’re technically too difficult…

But what about vitamin tablets? They’re easy to study, in the sense that it’s easy to take a tablet - easier than changing your whole food lifestyle - easy to find a placebo control for, and so on. And there have been innumerable studies, and systematic reviews of those studies, and meta-analyses of those studies, and they have found no benefit for antioxidants. A meta-analysis – a mathematical combination of lots of smaller studies to give one larger and more accurate answer - of 15 studies, a total of over 200,000 patients, being followed up for between 1 and 12 years, found no benefit for cardiovascular outcomes. The current Cochrane Review on antioxidants and bowel cancer had just as many patients, and again found no benefit for the pills.

That must be the single most prevalent claim of the whole alternative therapy industry: and it is in stark contradiction of the experience of hundreds of thousands of individuals who have been carefully studied in these trials, examining the very advice the alternative therapy industry is giving. If they can’t get that one thing right, why would you listen to them on anything else?

References:

Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet. 2003 Jun 14;361(9374):2017-23. Link.

Antioxidant supplements for preventing gastrointestinal cancers, Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. The Cochrane Database of Systematic Reviews 2006 Issue 2 Link.

Multiple risk factor intervention trial. Risk factor changes and mortality results. Multiple Risk Factor Intervention Trial Research Group. JAMA. 1982 Sep 24;248(12):1465-77. Link

Trisha Greenhalgh’s awesomely readable blockbuster “How To Read A Paper” is published by BMA books, available at Amazon and all good medical bookshops; alternatively, the BMJ review papers from which it is drawn are magnanimously available free online here (bear in mind these papers have fewer jokes and are generally a bit less readable than the book).

(Sorry, couldn't be bothered to sort out the links for the references, if you're interested you'll have to follow the link at the top of this post.)

[mr friendly guy]

I'm sorry, but when I googled Trigeminal Neuralgia and Dilantin, I got pain relief. I'm aware that Dilantin main function was to treat epilepsy but just assumed that it had a secondary effect of treating pain.

It does. Some anti-depressants and anti-convulsants can also be used to treat pain, particularly if its thought the pain is neuropathic in nature like for trigeminal neuralgia.

[Justforfun000]

But what about vitamin tablets? They’re easy to study, in the sense that it’s easy to take a tablet - easier than changing your whole food lifestyle - easy to find a placebo control for, and so on. And there have been innumerable studies, and systematic reviews of those studies, and meta-analyses of those studies, and they have found no benefit for antioxidants. A meta-analysis – a mathematical combination of lots of smaller studies to give one larger and more accurate answer - of 15 studies, a total of over 200,000 patients, being followed up for between 1 and 12 years, found no benefit for cardiovascular outcomes. The current Cochrane Review on antioxidants and bowel cancer had just as many patients, and again found no benefit for the pills.

Absolute bullshit!

You have to look carefully and find enough studies.

Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients.

Nathens AB, Neff MJ, Jurkovich GJ, Klotz P, Farver K, Ruzinski JT, Radella F, Garcia I, Maier RV.

Division of Trauma and General Surgery, Harborview Medical Center and the Department of Surgery, University of Washington, Seattle, Washington, USA. anathens@u.washington.edu

OBJECTIVE: To determine the effectiveness of early, routine antioxidant supplementation using alpha-tocopherol and ascorbic acid in reducing the rate of pulmonary morbidity and organ dysfunction in critically ill surgical patients. SUMMARY BACKGROUND DATA: Oxidative stress has been associated with the development of the acute respiratory distress syndrome (ARDS) and organ failure through direct tissue injury and activation of genes integral to the inflammatory response. In addition, depletion of endogenous antioxidants has been associated with an increased risk of nosocomial infections. The authors postulated that antioxidant supplementation in critically ill surgical patients may reduce the incidence of ARDS, pneumonia, and organ dysfunction. METHODS: This randomized, prospective study was conducted to compare outcomes in patients receiving antioxidant supplementation (alpha-tocopherol and ascorbate) versus those receiving standard care. The primary endpoint for analysis was pulmonary morbidity (a composite measure of ARDS and nosocomial pneumonia). Secondary endpoints included the development of multiple organ failure, duration of mechanical ventilation, length of ICU stay, and mortality. RESULTS: Five hundred ninety-five patients were enrolled and analyzed, 91% of whom were victims of trauma. The relative risk of pulmonary morbidity was 0.81 (95% confidence interval 0.60-1.1) in patients receiving antioxidant supplementation. Multiple organ failure was significantly less likely to occur in patients receiving antioxidants than in patients receiving standard care, with a relative risk of 0.43 (95% confidence interval 0.19-0.96). Patients randomized to antioxidant supplementation also had a shorter duration of mechanical ventilation and length of ICU stay. CONCLUSIONS: The early administration of antioxidant supplementation using alpha-tocopherol and ascorbic acid reduces the incidence of organ failure and shortens ICU length of stay in this cohort of critically ill surgical patients.

and

Vitamin E and C Combo Reduces Alzheimer's Risk
Rating: Unrated | Comments: 0
Print 01.19.2004 @04:49 PM
By Dwayne Hunter

Combining vitamin E and C supplements could be a simple way to reduce the risk of Alzheimer's disease.

Studies have shown that antioxidant vitamins can protect the brain against damage caused by free radicals and other byproducts of metabolism.

Neurons are especially sensitive to such damage, which is believed to contribute to neurological diseases such as Alzheimer's.

Peter Zandi of Johns Hopkins University in Baltimore, Maryland and colleagues have now found that combining vitamin E and vitamin C supplements can dramatically reduce the risk of Alzheimer's

Use of vitamin E and C supplements in combination reduced Alzheimer's prevalence by about 78% and incidence by about 64%, the researchers report.

Good combination

The researchers assessed supplement use and the prevalence of dementia and Alzheimer's disease in 4,740 people 65 and older between in 1995 to 1997.

They then followed up between 1998 and 2000.

They found 200 Alzheimer's cases between 1995 and 1997 and 104 new cases during their follow-up.

Looking at the effects of supplement use, they divided subjects according to their vitamin E and vitamin C intake.

Participants were classified as vitamin E users if they reported taking supplements of vitamin E totaling more than 400 IU. They were categorized as vitamin C users if they reported taking supplements totaling at at least 500 micrograms of ascorbic acid.

The researchers found the greatest reduction in both prevalence and incidence of Alzheimer's disease amongst those who used individual vitamin E and C supplements in combination, with or without an additional multivitamin.

The study found no appreciable association with the use of vitamin C alone, vitamin E alone or vitamin C and multivitamins in combination.

Higher intake

The current recommended daily allowance for the vitamins, the researchers say, is 22 IU for vitamin E and 75 to 90 micrograms for vitamin C.

The study suggests that higher doses may offer protection against Alzheimer's disease when taken together.

The research is published in the January issue of The Archives of Neurology (read abstract).
Copyright � Betterhumans

and

Scientists Say Vitamin C May Alleviate The Body's Response To Stress
Science Daily — NEW ORLEANS, La., Aug. 22 -- Large doses of vitamin C can prevent illness by alleviating the body's normal response to stress, according to a scientist at the University of Alabama in Huntsville. This study was described here today at a national meeting of the American Chemical Society, the world's largest scientific society.


The study tested the effects of vitamin C on the adrenal function of laboratory animals subjected to stress, said P. Samuel Campbell, Ph.D., chairman of the university's department of biological sciences. In both animals and humans, the adrenal gland reacts to stress by releasing corticoids, such as corticosterone and cortisol. These and other hormones trigger the "fight or flight" reaction that allows us to spring into action when in danger. They also suppress the immune system, the body's first line of defense against disease.

The Alabama researchers put laboratory rats under stress by immobilizing them for one hour a day over a three-week period. To check whether vitamin C would reduce the production of stress hormones, the rats were fed 200 milligrams a day, the equivalent of several grams a day for humans. This dosage far exceeds the present recommended daily allowance (RDA) of 60 milligrams, a figure based on the amount required to prevent deficiency diseases such as scurvy. The study showed that vitamin C reduced the levels of stress hormones in the blood-and also reduced other typical indicators of physical and emotional stress, such as loss in body weight, enlargement of the adrenal glands, and reduction in the size of the thymus gland and the spleen, according to Campbell.

In addition, the vitamin C treatment elevated the levels of circulating IgG antibody, the body's principal defense against systemic infection, he said.

In the control group-rats who were not subjected to stress-vitamin C increased the production of IgG antibody to a somewhat higher level than it did in the stressed rats. This suggests that stress may create a tolerance for vitamin C. Consequently, animals-and perhaps people-who are under emotional stress may require higher doses of vitamin C to protect immune function.

Paradoxically, the vitamin C treatment may work by suppressing production and/or utilization of the vitamin C that naturally exists in the adrenal cortex of humans and animals, Campbell noted. This endogenous vitamin C appears to support the production of stress hormones, he said.

Campbell said his results help explain other evidence of the value of vitamin C in protecting immune function. For example, according to reports in the medical literature, vitamin C boosted immune function in a test group of elderly women. It also reduced the incidence of stress-related upper-respiratory infections in marathon runners.

Recommending a sharper look at the present RDA, Campbell said he believes that our prehistoric ancestors probably consumed large amounts of vitamin C in a tropical diet rich in fruits. "If so, the physiological constitution we have inherited may require doses far larger than the present RDA to keep us healthy under varying environmental conditions, including stress."

A result of studies on Vitamin E and Alzheimers:

http://www.ajcn.org/cgi/content/full/71/2/630s

The preclinical evidence supporting the use of antioxidants to prevent or slow AD is strong. There is clear evidence for increased oxidative damage in the brain of AD patients and numerous potential sources of excess free radicals that may contribute to this damage. Experiments performed in cell culture and in animals indicate that vitamin E and other antioxidants can prevent free radical–mediated cell death and diminish cognitive deterioration. Vitamin E has an excellent safety record. The results of the previous Alzheimer's Disease Cooperative Study clinical trial in patients with moderate AD suggest that vitamin E delays functional deterioration. These findings suggest that the rationale for another clinical trial now exists to determine whether vitamin E can prevent the development of dementia in elderly individuals with MCI.

And here's an expose on these "meta-analysis" studies and why you have to be careful on what to draw as conclusions:

What is a meta-analysis?A meta-analysis is not a clinical trial. It is a statistical technique for combining the results of manyexisting studies in order to clarify possible effects. When studies are done with a few hundred oreven a few thousand people, it is often difficult to determine whether differences between thetreatment group and the placebo group are “real” or just accidents due to chance. Combining studiesprovides more people for analysis and thus increases statistical power. While a meta-analysis is animportant scientific tool, it also has limitations.What is all-cause mortality?Studies are generally designed to look at some particular outcome, like whether vitamin E reducedthe risk of having a heart attack. However, in studies involving sick people and lasting for severalyears, there will be other outcomes, such as death. A certain number of people in longterm studiesare going to die, and all-cause mortality is the number of people who died from any cause—whetheror not the cause has anything to do with the purpose of the study. All-cause mortality includes peoplewho died of heart disease or infectious disease or cancer or getting hit by a bus. The number ofpeople who die in the treatment group and in the control group will rarely be exactly equal. Statisticalanalysis tells us whether differences in total mortality between the treatment group and the controlgroup are significant or just the result of chance.What did this study find, overall?This study analyzed 19 clinical t rials in which vitam in E was given, involving a total of alm ost 140,000people. Eighteen of the 19 trials individually found no statistically significant increase in tot al mortality inthe vitamin E group. Even when all of the 19 tr ials were combined, there was no significant increase intot al mortality. The study authors say, “T he average deat h risk acr oss t rials in t he control groups was1022 per 10,000 persons. Overall, vit amin E supplementation did not affect all-cause mortality.”What did the study find, relating to high and low doses of vitamin E?When the trials were divided according to the dose of vitamin E, the researchers found that low dosesof vitamin E slightly decreased total mortality while high doses of vitamin E (400 IU or more) slightlyincreased total mortality. The researchers said this was a statistically significant effect, but othershave criticized whether it has practical meaning. Most of the high-dose studies were done in peoplewho already had various diseases and the authors say that these findings may not be generalizableto healthy adults. However, they go on to generalize, saying that people should avoid high-dosevitamin E and indeed high doses of any vitamin—a conclusion much more sweeping than is justifiedby their analysis.Were there other findings?The researchers also did a dose-response analysis of the clinical trials, which found a statistically significant (butvery small) increase in mortality only when the vitamin E dose was greater than 900 IU. This is contrary to thefinding in their main meta-analysis that doses over 400 IU might confer increased risk.--------------------------------------------------------------------------------
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Continued from previous pageCouncil for Responsible Nutrition Fact SheetMore facts on the vitamin E meta-analysisWhat were the 19 studies used in this meta-analysis?T he st udies chosen f or the m et a-analysis all lasted m or e t han one year and repor t ed at least 10 deat hsf rom all causes. St udies in which no deaths occur r ed were not included in the analysis. The st udies wer eoriginally published in t he decade from 1993 to 2004. Som e of the studies involved over 20,000 people, and some involved only a few hundred people. Doses used in the st udies r anged f r om 16.5 I U t o 2000 IUand were given for periods f rom one to 8 year s. I n som e studies the vitamin E was given as par t of am ultivit am in or some ot her m ixt ur e of nut rient s, and in some st udies vitamin E was given as a singlenut rient . The studies wer e conduct ed in various part s of the wor ld—Eur ope, Asia, t he Middle East, Austr alia, Canada, and the U.S. Vit am in E was given in these studies for m any diff er ent purposes, including reducing t he risk of hear t disease, cancer, and macular degener at ion and delaying t heprogr ession of cat ar act s, kidney disease, Alzheimer ’s disease and Parkinson’s disease. Some of th estu di es fo u nd a benef it o f vit ami n E f or th ese p urp oses. Do any of the studies show a benefit from vitamin E?Yes. Many of the 19 clinical studies used in this meta-analysis actually showed a health benefit fromvitamin E. For example, one study in England showed that vitamin E at levels of 400 and 800 IUreduced the risk of heart attack by 75% in men who already had symptoms of heart disease. A studyin patients with kidney failure found a reduced risk of heart attacks and of death from heart disease inpeople who were given 800 IU of vitamin E. Another of the studies found that vitamin E (400 IU) incombination with some other nutrients reduced the risk of age-related macular degeneration, theleading cause of blindness in elderly people. And one study showed that a very high dose of vitaminE (2000 IU) delayed the progression of Alzheimer’s disease.Do epidemiologic studies show a benefit from vitamin E?Yes. Numerous epidemiologic studies have shown a benefit from vitamin E. In an epidemiologicstudy, researchers simply observe whether people who use certain products or adopt certain habitson their own have more or less disease than people who do not. A Harvard study of more than80,000 nurses found a 41% reduction in the risk of heart disease in nurses who had used vitamin Esupplements for at least 2 years. A Harvard study of almost 40,000 male health professionals (mostlydentists) found that men who took vitamin E supplements for more than 2 years had a 37% reducedrisk of heart disease. A study conducted by the National Institute of Aging in 11,000 elderly peoplefound that those who used supplements of vitamins C and E had a 53 percent reduction in mortalityfrom heart disease and a 42 percent reduction in all-cause mortality, compared to non-users.Are more studies being done using high-dose vitamin E?Yes. A number of new clinical trials are now under way, and researchers are attempting to reassurethe people enrolled in these trials that vitamin E is safe and that the research should continue. Theyinclude the Women’s Health Study involving over 40,000 female health professionals, the Physicians’Health Study involving thousands of U.S. doctors, and the Women’s Antioxidant CardiovascularDisease Study. Also, the National Cancer Institute is sponsoring the Selenium and Vitamin EChemoprevention Trial (SELECT) to evaluate the effects of these two nutrients in protecting againstprostate cancer in more than 30,000 men.Continued
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Continued from previous pageCouncil for Responsible Nutrition Fact SheetMore facts on the vitamin E meta-analysisWas it reasonable to select 400 IU as the cutoff between low-dose and high-dose vitamin E?No. Four hundred IU was an arbitrary number. It is not evident how the researchers chose to define 400IU and not some other value as the “high-dose” mark, except that it is the most commonly marketeddose in the U.S. Two important studies including the GISSI trial in Italy used 330 IU of vitamin E—notmuch lower than 400 IU. Including those in the high-dose group would have been reasonable, and thepositive effects of the GISSI trial would have offset some of the studies showing a trend towardincreased mortality. Below that dose, there is only one study at 200 IU, also showing a slightlybeneficial effect on total mortality. The truly “low-dose” studies are the five that used only 60 IU or lessof vitamin E. In short, it appears that 400 IU rather than 200 or 300 IU may have been arbitrarilyselected as the high-dose cutoff in order to bolster a finding of risk.How much vitamin E is safe?The Institute of Medicine, a scientific advisory body, has concluded that vitamin E is safe for chronicuse in the general population at levels up to 1000 mg (1000 IU synthetic vitamin E, 1500 IU naturalvitamin E). The Recommended Dietary Allowance for vitamin E is 15 mg (15-22.5 IU, depending on thechemical form), and only a small fraction of the population gets this much from diet alone. Mostmultivitamins contain 15 to 60 IU of vitamin E.What should people think about this meta-analysis?This meta-analysis does not change what is known about vitamin E safety. It used no new researchbut instead combined 19 studies in order to create statistical significance for a finding of a slightincrease in all-cause mortality in studies that used 400 IU or more of vitamin E, but overall the studiesshowed no such increase and a dose-response analysis showed a significant increase only at levelsabove 900 IU. The authors have exaggerated the practical significance of their findings to attractattention and scare the public. As a result, numerous participants in ongoing clinical trials on high-dosevitamin E sponsored by the National Cancer Institute have been needlessly frightened, and the future ofthe studies may be endangered. Consumers who are already using vitamin E should continue touse it with confidence, and people who are not currently using at least a multivitamin containingvitamin E should consider doing so, since the overwhelming majority of the population fails toget the recommended amount of vitamin E from diet alone.rev11/22/04

[Prozac the Robert]

Absolute bullshit!

I'm afraid I don't really know about the subject to defend the article I posted in any meaningful way. I certainly don't feel up to guessing how good the studies you mention are.

On the other hand, those are mostly not intervention studies of the type he refers to. Are there more actual intervention trials with positive results? Or do you feel that the observational studies are also satisfactory evidence?

And I'm afraid I can't manage to read the thing on meta analysis. Could you provide the link if the formatting is any better where you got it from?

Or just put in a few paragraph breaks and strip out the random spaces? Only if you can be bothered though, I'm not up to debating on this subject so it might not be worth your time.

[Justforfun000]

I'm afraid I don't really know about the subject to defend the article I posted in any meaningful way. I certainly don't feel up to guessing how good the studies you mention are.

On the other hand, those are mostly not intervention studies of the type he refers to. Are there more actual intervention trials with positive results? Or do you feel that the observational studies are also satisfactory evidence?

I was just finding some examples of what is out there. He tried to blatantly dismiss the entire field of antioxidants as coming up short and having no real evidence of positive effect which is ridiculous. Yes there are some studies that have challenged other positive ones, and there are certainly more questions than answers, but it's far from a totally negative goose egg at this point like he suggests.

And I'm afraid I can't manage to read the thing on meta analysis. Could you provide the link if the formatting is any better where you got it from?

Sorry about that. I didn't realize it would transfer over so bad. Lessee...Great. Now I can't find it either. Lol.

Well here's another one that sums up the same kind of problems:

http://www.npicenter.com/anm/anmviewer. ... &print=yes

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JAMA Publishes Meta-Analysis on Antioxidants – Industry Responds
2007/02/28 - NPIcenter

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The Journal of the American Medical Association (JAMA) has published a 'Systematic Review and Meta-Analysis'1 examining the effect of antioxidant supplements on mortality in randomized clinical trials. The trials selected involved beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention.(68 randomized trials with 232,606 participants).



The authors concluded that treatment with beta carotene, vitamin A, and vitamin E may increase mortality, while the roles of vitamin C and selenium need more scrutiny.



The International Alliance of Dietary Supplement-Food Associations (IADSA), Council for Responsible Nutrition (CRN) and Natural Products Association have all weighed in on this study. Predictably, mainstream media has been very quick on the uptake with sensational headlines the most extreme of which reads, “Vitamins Can Kill You”.



At issue in this case, is another meta-analysis, another examination of previously published research. As is the case with any meta-analysis, selection of included (and excluded) studies becomes quite important, with industry arguing that the researcher’s criteria predisposed the analysis to the ultimate results - a significant increase in mortality. Another consistent observation made of the study results, and one which actually did get mention in one of the Reuters stories, was the fact that many of the studies involved, not a normal healthy population where vitamin supplementation is suggested to preserve good health, but rather diseased populations with a variety of health issues.



In CRN’s response, Dr. Andrew Shao observes, “Combining secondary prevention and primary prevention trials and then making conclusions for the entire population is an unsound scientific approach,” said Dr. Shao. “Additionally, many of the treatment trials had limitations, including the expectation that a simple antioxidant vitamin could be expected to overturn serious illness, such as cancer or heart disease. These trials likely statistically skewed the results.”



The Natural Products Association’s vice president of scientific affairs Daniel Fabricant confirmed, ““Despite the authors’ contention, this analysis is assessing mortality of at-risk and diseased populations – versus a healthy population – in prevention trials. The risk of mortality must be attributed to the appropriate population studied, those with an existing health condition, which it isn't in this case. Instead, those findings are generalized to a healthy general population, which is wrong on many levels.”

The challenges of interpreting a meta-analysis can be considerable, and not only because of different population groups, disease states or endpoints. Durations, dosages and controls also vary widely so the interpretation is at best challenging, at worst, daunting. Dr. Shao notes, “While meta-analyses can be useful when the included studies are very similar in design and study population, this meta-analysis combined studies that differ vastly from each other in a number of important ways that compromise the results.” Also at question is the source of the antioxidant vitamins as the authors argue that their analysis and conclusions are based on synthetic antioxidants and "should not be translated to potential effects of fruits and vegetables".

Dr Alexander Schauss, Senior Director, Natural and Medicinal Products Research, AIBMR Life Sciences, Inc. is quite open in his assessment of this result. “In the simplest of terms: the JAMA paper is a carefully crafted example of meta-assassination. The JAMA authors disregarded countless studies that would have altered their conclusion.” Schauss continues, “It is unfortunate that statisticians working in the public health arena are misusing meta-analysis to draw such misguided conclusions. Do they really want the public to disregard the advice of the USDA, physicians, dieticians, and nutritionists, who have been urging the public to increase their intake of antioxidant-rich fruits, vegetables and nuts, to prevent chronic and degenerative diseases?”

As is frequently the case, in few instances is the current headline story placed in the context of a complete body of research, positive, negative and inconclusive. The fact that the latest study is exactly that – the latest, is frequently lost in the drive to sensationalize the current presentation of results. In IADSA’s response, Dr Derek Shrimpton, Scientific Advisor to the European Federation of Associations of Health Product Manufacturers, was quoted: “The paper proposes to overturn the conclusions of well conducted clinical trials in favour of conclusions drawn from a statistical analysis of all publications in the scientific literature on the subject irrespective of their merit.”

Dr. Schauss contributes, “How unfortunate that the authors disregarded a fundamental physiological fact: Oxidative stress must be countered by antioxidant activity in vivo for the human body to maintain its normal function and remain healthy. There exists a firm scientific foundation based on thousands of studies published in hundreds of peer review journals on the role of oxidative stress in the development of chronic and degenerative diseases. Many diseases that are contributing to the hundreds of billions of dollars being spent on health care costs are known to increase in severity due to the cumulative effect of free radical damage on biological molecules (DNA, proteins, lipids, etc.).”

Loren Israelsen, Executive Director of the United Natural Products Alliance (UNPA) predicts “This study will be dissected more carefully than a lab frog as the debate continues whether this is competent science, prejudicial in intent or an example of the difficulty in studying diseased people to find out what makes healthy people healthy.”



Perhaps most significant from an industry and potential health standpoint is the impact of these headlines on already baffled, blitzed and confused consumers currently, based on research, using these vitamins to support and maintain good health. Fabricant comments, “…what’s most troubling is that people who are safely and beneficially taking vitamins might stop, which may actually put their health at greater risk.” More optimistically, Israelsen counters, “It is counter intuitive and unconvincing to many consumers that anti oxidants will contribute to an earlier death”.



The full impact of this study will take some time to materialize. There is no doubt however that it places more strain on already challenged categories in the dietary supplements marketplace. It is also quite apparent, yet again, that industry's response, or even ability to generate positive stories is heavily outweighed by the appetitie for the sensational negative - regardless of the questions or concerns about study protocol or intent.



1 JAMA Vol. 297 No. 8, February 28, 2007