1708 replies to this topic

[niner]

Coincidentally, I just bought an ultrasonic cleaner today too! I got improved dispersion after an eight minute sonication. Afterward, I let the suspension sit for a while to see how much settling I got. There was more than I'd have liked, but there was also a finely divided component that didn't look like it was going to settle quickly. I had an old 300x microscope that I got as a Christmas present when I was twelve. (Thanks, Aunt Gloria!) I tried looking at a drop of the suspension, but it was inconclusive. Then I chugged it. Later I fixed a lighting problem on the scope, so I'll probably try again later. I need to find something to use as a scale or size standard. Based on the rate of settling, I don't think that I'm there yet with 8 minutes. I was using a fairly heavy glass, which might have reduced the energy transfer. I've read that setting a heavy object directly on the bottom of the well might damage the transducer, so I placed the glass in the cleaning basket. That also might have reduced energy transfer, but I don't want to blow it up. My recollection from the Sirtris patent was that they sonicated for hours to get it to go into cyclodextrin, starting from something that was already micronized. I just want to micronize it at this point... I'm still using Miralax, but will try some lecithin soon.

[malbecman]

Yes, they are quite noisy, a kind of high pitched buzzing noise-quite annoying, actually. Invert a carboard box over it, that really helps and it shouldn't overheat. You can even line the box with some styrofoam or somesuch to really help deaden the noise but do leave some room and/or cut some slits for air to circulate in there, esp. if running it for awhile. They do warm up.

Got my ultrasonic cleaner, and it works.  Five minutes of buzzing, much better dispersion.  Very little precipitates out.  It also helps dissolve the lecithin faster.  Noisy, though.  (Note to self:  hide wife's hearing aid before use.)

[levkamensky]

So nobody experienced the same effects as Senclair's mice? No doubled endurance, restructuring of muscle fiber into athletic, weight loss without going to the gym. Then what's the point? Prolonging life by one year? I want to see some real results not placebo effects.

[malbecman]

No trolls allowed on this forum....... [wis]

So nobody experienced the same effects as Senclair's mice? No doubled endurance, restructuring of muscle fiber into athletic, weight loss without going to the gym. Then what's the point? Prolonging life by one year? I want to see some real results not placebo effects.

[craigb527]

Sinclair's mice didn't get the double endurance, Johan Auwerx's mice did. I believe that resveratrol is more of a performance enhancing drug than it is for life extension. Other studies do not seem to back up Sinclair's results. Since I began taking larger doses, I have more physical endurance, and have not been sore the next day, at all, from working out or even sore while I work out. No matter how much I work out. On the flip side of that, it seems like my muscles aren't building up from working out. In fact even though I am stronger, endurance wise, my muscles seem to be shrinking, or staying the same, not sure, even though I am working out a lot. Its not placebo effect. My muscles do not get sore, which is probably why I feel they are shrinking.
Auwerx's study http://64.233.179.10...l_mag_2006.pdf

Edited by craigb527, 19 October 2007 - 11:31 PM.

[Mind]

If a person is already in 'good' athletic shape then there is probably not much more endurance that one can gain from resveratrol (not as much as the mice gained. If I remember correctly, Sincair was working with obese mice). Of course, there are other theorized benefits that might make it worth taking.

[craigb527]

Not sure about the "good athletic shape" thing. I would not qualify, not many would. But, I do believe that resveratrol causes one's muscles to burn oxygen more efficiently, which would seem to have impact on all, not just the out of shape. As far as I know, Sinclair's mice lived longer, at least one or two groups of them, but I don"t recall him making to many claims on physical endurance.

Edited by craigb527, 20 October 2007 - 12:14 AM.

[bixbyte]

Just Curious,

Anybody Sleeping?

[niner]

Just Curious,

Anybody Sleeping?

Umm, not at the moment... But I've been sleeping pretty well at night.

[sUper GeNius]

Sinclair's mice didn't get the double endurance, Johan Auwerx's mice did.  I believe that resveratrol is more of a performance enhancing drug than it is for life extension.  Other studies do not seem to back up Sinclair's results.  Since I began taking larger doses, I have more physical endurance, and have not been sore the next day, at all, from working out or even sore while I work out.  No matter how much I work out.  On the flip side of that, it seems like my muscles aren't building up from working out.  In fact even though I am stronger, endurance wise, my muscles seem to be shrinking, or staying the same, not sure, even though I am working out a lot.  Its not placebo effect.  My muscles do not get sore, which is probably why I feel they are shrinking.
Auwerx's study  http://64.233.179.10...l_mag_2006.pdf

Interesting note about the lack of soreness. That happened to me the other day too. Exercised vigorously for the first time in months, expect to be quite sore the next day. Nothing, nada. Not one tiny bit of soreness. I was amazed.

[craigb527]

Yeah. It is true and not a placebo effect. Before res I would get very sore from working out, muscles would rebuild, and I would recover after a day or two. Doesn't happen like that now. No soreness, even when I try.

[niner]

Just Curious,

Anybody Sleeping?

Umm, not at the moment... But I've been sleeping pretty well at night.

On large doses of 98-99% RSV/Miralax ?

Yeah. 99% synthetic and Miralax. I wish I could say exactly what the dose is, but I'm using powder and estimating, since I don't have a milligram scale. I think that I'm over a gram these days, but probably under two. (Pretty scientific, huh?)

All kinds of stuff could be interfering with sleep. I once had a problem with blueberry extract, of all things. Do you have a CoA that you trust for the resveratrol you're using?

[sUper GeNius]

Yeah.  It is true and not a placebo effect.  Before res I would get very sore from working out, muscles would rebuild, and I would recover after a day or two.  Doesn't happen like that now.  No soreness, even when I try.

Sounds almost like an anabolic steroid. Are you able to work out more often?

[rodentman]

Sinclair's mice didn't get the double endurance, Johan Auwerx's mice did. I believe that resveratrol is more of a performance enhancing drug than it is for life extension. Other studies do not seem to back up Sinclair's results. Since I began taking larger doses, I have more physical endurance, and have not been sore the next day, at all, from working out or even sore while I work out. No matter how much I work out. On the flip side of that, it seems like my muscles aren't building up from working out. In fact even though I am stronger, endurance wise, my muscles seem to be shrinking, or staying the same, not sure, even though I am working out a lot. Its not placebo effect. My muscles do not get sore, which is probably why I feel they are shrinking.
Auwerx's study http://64.233.179.10...l_mag_2006.pdf

This is just a stab at the dark, but Ive heard that taking high anti-oxidants keeps your muscled from appropriately re-building themselves, and Its been suggested, NOT to overload on AO before lifting to encourage muscle growth.

Is there a possibility that these are related?

[craigb527]

I have been able to work out as often as I want and not get sore. I have been taking antioxidants for some time and not experienced this effect. Only when I began taking resveratrol. My muscles don't get sore. Maybe its a placebo effect.

Edited by craigb527, 20 October 2007 - 06:00 AM.

[maxwatt]

I have been able to work out as often as I want and not get sore.  I have been taking antioxidants for some time and not experienced this effect.  Only when I began taking resveratrol.  My muscles don't get sore.  Maybe its a placebo effect.

Reveratrol is a mild cox2 inhibitor.

[craigb527]

I have been able to work out as often as I want and not get sore.  I have been taking antioxidants for some time and not experienced this effect.  Only when I began taking resveratrol.  My muscles don't get sore.  Maybe its a placebo effect.

Resveratrol is a mild cox2 inhibitor.

Yes, I think that is why I have no pain in my joints. My knees had hurt for years. They feel good now.

I got my ultrasonic device in. Waiting on ordering some res powder so I can use it. Are you guys using powdered lecithin in the mix?

[krillin]

Interesting note about the lack of soreness. That happened to me the other day too. Exercised vigorously for the first time in months, expect to be quite sore the next day. Nothing, nada. Not one tiny bit of soreness. I was amazed.

That's what CoQ10 does for me: no soreness after long runs, in addition to spectacular and enduring endurance gains. Other antioxidants didn't do the same thing, so it's likely mitochondrial. Temporary effects were a dopamine high and 25% reduction in required sleep time.

[maxwatt]

An additional effect of resveratrol: it inhibits nfKappa-P via Sirt1 activation, and this reduces inflammation beyond mere Cox2 inhibition.

[craigb527]

Is Resveratrol an Exercise Pill?
Double Your Pleasure, Double Your Fun, and Double How Far You Can Run
s we go to press, a paper has just been published showing that resveratrol greatly increases physical performance in normal young mice.1 This follows hard on the heels of the recent finding, by David Sinclair and colleagues, that resveratrol extends lifespan in obese middle-aged mice by providing the health and longevity benefits of caloric restriction—without caloric restriction (see the article on page 4)! All this suggests that resveratrol is a sort of “fountain of youth,” at least for mice, and probably for humans.

In the new study, by Johan Auwerx and colleagues, resveratrol-supplemented mice ran twice as far as those not receiving it. Resveratrol facilitated their muscles to produce more energy, more efficiently. The study confirmed a connection found previously between the principal biochemical pathway activated by resveratrol and an animal’s physiology. Since that same pathway exists in humans, it’s likely that human physiology will respond similarly.

Whatever your physical condition, any continuous exertion, such as running, will eventually result in exhaustion. But if the new study holds for humans, supplementing with resveratrol might double the distance you could run before exhaustion set in, and you would appear to be a trained athlete, with a reduced heart rate and more powerful muscles. According to Auwerx, “Resveratrol makes you look like a trained athlete without the training.”

Will Exercise Become Obsolete?

In an article we published last August (“Resveratrol—Star Molecule Against Disease and Aging”), we quoted from a 2006 paper by Joseph Baur and David Sinclair, who said, “In addition, resveratrol treatment increases mitochondrial biogenesis … and, at least under certain conditions, improves insulin sensitivity, which is consistent with observations in calorie-restricted animals.”4 [emphasis added] It is these benefits that the Auwerx study points to as the principal explanations for increased muscle power. Mitochondrial biogenesis means the production of more mitochondria, the organelles that produce energy within the cell.

Indeed, the mice fed resveratrol were found to have more mitochondria in their muscle cells. These mice burned more fat, did not gain weight (unlike the mice in the Sinclair study), and had improved insulin sensitivity. Especially interesting was the fact that their muscle fibers appeared to be more like the type developed by trained human athletes. Could resveratrol be an exercise nutrient that can provide the benefits of exercise without the need to exercise? Could resveratrol make exercise obsolete?

Unfortunately, the amount of resveratrol used in the Auwerx study was 400 mg per kilogram of body weight, per day, which is 18 times greater than the largest amount used in the Sinclair study (22.4 mg per kilogram of body weight, per day). Dr. Sinclair and his family and colleagues take 5 mg of resveratrol per kilogram of body weight, per day, or 22% of the 22.4-mg/kg amount he gave his obese mice. If we applied that 22% factor to the 400-mg/kg amount used in the Auwerx study, a would-be human athlete would need to take about 88 mg of resveratrol per kilogram of body weight, per day. For a 75-kg (165-lb) human, the total daily consumption would then be 6.7 g, a pharmacological amount that is not advisable, especially for men, based on studies showing that resveratrol can act as a powerful systemic aromatase inhibitor when very large amounts are taken.5

The enhanced metabolism seen in the Auwerx study was due primarily to the resveratrol-mediated activation of an enzyme called PGC-1á, which stimulates mitochondrial biogenesis.

Next month, in our ongoing series on Durk Pearson & Sandy Shaw’s 21st Century Weight Loss Program (see Part 2 of their Glycemic Control Strategy on page 16), we will learn that there are other ways to enhance PGC-1á activity. Durk & Sandy will offer a formulation to do just that—one that will also, by the way, contain a large amount of resveratrol (about half of what Sinclair is taking). These ingredients and others will be used in combination in the second major product division of the weight loss program.

Also, we will cover the Auwerx study (along with any other important developments) next month, so stay tuned. These are extremely exciting times for life extenders and life enhancers.

"the total daily consumption would then be 6.7 g, a pharmacological amount that is not advisable, especially for men, based on studies showing that resveratrol can act as a powerful systemic aromatase inhibitor when very large amounts are taken."

Can someone explain the above statement and ramifications please?

[ilanso]

September 11, 2007 — A new study has shown that 13% of breast cancer patients stop taking aromatase inhibitors because of musculoskeletal adverse effects. The findings were presented in San Francisco, California, this weekend at the Breast Cancer Symposium.
"Frequent diagnoses include tendonitis, osteoarthritis, bursitis, and carpal tunnel syndrome,"

This may be the explanation for some tendonitis flares reported in this forum (see the supplements/tendinitis thread)

[rabagley]

Well, aromatase is how the body creates estrogens from androgens. So, the two possible conditions would be hypoestrogenism or higher androgen levels. These conditions tend to be riskier for premenopausal females than postmenopausal females or mature males. For premenopausal women, there do seem to be risks to fertility and medium-term health. For postmenopausal women, aromatase inhibition is a common breast cancer treatment and prevention tool.

On the other hand, most of the effects on mature males would be considered positive. Reduction of body fat, faster and leaner muscle development, increased bone density, anemia reversal, inhibition of several cancers, increased sperm count, etc.

Immature males would grow taller without sufficient estrogen and there may be other effects making it riskier for men under 25.

Exogenous sources of testosterone carry many risks most of us will have heard of, but I don't think that cutting out the testosterone -> estrogen metabolic pathway will mimic the levels of testosterone produced by supplementation. In males, most testosterone is metabolized by several pathways which appear to be unaffected by resveratrol. So although androgen levels would be higher, I don't see any reason to believe that they would be dangerously higher.

Edited by rabagley, 23 October 2007 - 05:16 AM.

[rabagley]

At levels equivalent to the Sinclair study (20mg/kg/day) rat sperm counts were 76% higher with no changes in sperm quality.

http://jn.nutrition....t/135/4/757.pdf

emphasis added

This is the first report of a stimulatory effect of transresveratrol on the secretion of gonadotrophins, the major endocrine regulators of spermatogenesis. The concentrations of FSH, which acts within the tubules to stimulate spermatogenesis, and LH, which signals the production of testosterone in Leydig cells, were elevated in the resveratrol group compared with the control rats. Testosterone, which is essential for promoting spermatogenesis, was also enhanced. These results indicate that the effect of trans-resveratrol on sperm count may be caused by the hypophisary stimulation of testicular function. The endocrinal regulation of the hypothalamic-pituitarygonadal axis in the males is intricate and involves estradiol and testosterone (12,13). The sites for the feedback regulation include cells in the hypothalamus, which are in close proximity to gonadotrophin-releasing hormone neurons, and gonadotrophins in the pituitary, which may respond directly to androgens caused by the expression of the androgen receptor (AR), whereas the presence of aromatase and the estrogen receptor (ER) allows the conversion of androgens into estrogens, and the subsequent activation of ER signaling pathways (12). A possible explanation for our findings could be attributed to the binding of trans-resveratrol to ER as a mixed weak agonist/antagonist, without estrogenic properties (1,2,14,15). Interestingly, we did not observe estrogenic activity of trans-resveratrol.  Our results indicate that the daily oral administration of 20 mg/kg for 90 d did not affect body weight or food and water consumption in the treated group compared with the control rats. Given that growth inhibition is a sensitive indicator of estrogenic effects (16), this lack of reduction in body weight in the treated rats substantiates that trans-resveratrol does not act as an estrogen agonist, which is in agreement with other in vivo studies (17,18). Consequently, this compound could interact with the ER, thus increasing the secretion of gonadotrophins, leading in turn to an increment in testosterone and sperm output. Furthermore, the effects described above may have been enhanced through androgen antagonism because trans-resveratrol also antagonizes androgen action in prostate cancer cells by inhibiting AR activity and suppressing AR expression (19,20).

So it doesn't favor estrogen, but we knew that. At 20mg/kg/day, the relationship between resveratrol and sex hormones is complex but seems net positive for mature males. Perhaps it expresses more clearly as an estrogen antagonist at higher levels, yielding a different decision matrix. Certainly, the risk equation for middle aged women is very different.

Edited by rabagley, 22 October 2007 - 07:59 AM.

[ilanso]

Aromatase inhibitors may protect against prostate cancer but promote nasty (but reversible once the drug is stopped) joint problems.

[quarter]

Since I ran out of my Country Life Resveratrol Plus caps (and hence ceased resveratrol supplementation) my previous achilles tendon issues have cleared up. This could be entirely coincidental but did occur at roughly the same time, both the onset after beginning the country life caps (I took between 5 and 10 caps a day for a period of approximately 6 months) and the disappearance not long after running out. Both of my Achilles tendons experienced these problems during the resveratrol supplementation but I did not perceive anything else I could attribute to the resveratrol, so no positives I could detect. I am now reconsidering my previous plans to purchase res powder.

Edited by quarter, 22 October 2007 - 04:51 PM.

[tintinet]

Reagan-Shaw S, Nihal M, Ahmad N.
Dose translation from animal to human studies revisited.
FASEB J. 2007 Oct 17; [Epub ahead of print]
PMID: 17942826

"...CORRECT DOSE CALCULATION: AN EXAMPLE

As described above, confusion and concerns emanated
from a recent study by Baur et al. (2), where a dose of
22.4 mg/kg (body weight) of resveratrol was used in a
mouse study on aging and obesity-related disorders.
The media reported that a 60 kg human would have to
consume 1344 mg of resveratrol per day in order to
receive a like benefit, a serious misinterpretation of the
research. Using an average of 2 mg resveratrol per
bottle of wine (6), this calculation implies that a person
would have to drink 672 bottles of red wine to approximate
the resveratrol equivalent.

However, the Food and Drug Administration (7) has
suggested that the extrapolation of animal dose to
human dose is correctly performed only through normalization
to BSA, which often is represented in mg/
m2. The human dose equivalent can be more appropriately
calculated by using the formula shown in Fig. 1.
To convert the dose used in a mouse to a dose based on
surface area for humans, multiply 22.4 mg/kg (Baur's
mouse dose) by the Km factor (3) for a mouse and then
divide by the Km factor (37) for a human (Table 1).
This calculation results in a human equivalent dose for
resveratrol of 1.82 mg/kg, which equates to a 109 mg
dose of resveratrol for a 60 kg person. While not
reasonably achievable through consumption of wine,
this concentration may be provided through a daily oral
supplement. We would like to emphasize that an appropriately
calculated dose based on research in mice is
achievable in humans. However, while supplements at
this dose (109 mg) and higher are readily available in
pill or capsule form for general public consumption, we
do not advocate their usage...."

[Anthony_Loera]

From the FDA website:
http://www.fda.gov/c...s/dose.htm#ret2

If the parent drug is measured in the plasma at multiple times and fits the range of toxic dose for two or more animal species, it may be possible to develop a pharmacokinetic model predicting human doses and concentrations and draw inferences about human safe plasma levels in the absence of prior human data. While quantitative modeling for this purpose may be straightforward, the following points suggest this approach may present a number of difficulties when evaluating estimates of a safe starting dose. Generally, at the time of IND initiation, there are a number of unknowns regarding animal toxicity and comparability of human and animal pharmacokinetics and metabolism: (1) human bioavailability and metabolism may differ significantly from that of animals; (2) mechanisms of toxicity may not be known (i.e., toxic accumulation in a peripheral compartment; and/or (3) toxicity may be due to an unidentified metabolite, not parent drug. Thus, to rely on pharmacokinetic models (based on parent drug in plasma) to gauge starting doses would require multiple untested assumptions. Modeling may be used with greatest validity to estimate human starting doses in special cases where few underlying assumptions would be necessary. Such cases are exemplified by large molecular weight proteins (like humanized monoclonal antibodies), which are intravenously administered, are removed from circulation by endocytosis rather than metabolizism, have immediate and detectable effects on blood cells, and have a volume of distribution limited to the plasma volume. Here, allometric, pharmacokinetic, and pharmacodynamic models have been useful in identifying the human mg/kg dose that would be predicted to correlate with safe drug plasma levels in nonhuman primates. Even in these cases, uncertainties (such as differences between human and chimpanzee receptor sensitivity or density) have been shown to affect human pharmacologic or toxicologic outcomes, and the use of safety factors as described in this document is still warranted.

As far as I know, we have human plasma numbers from a 25mg study using humans, don't we? Wouldn't this be more helpful than BSA estimates?

A

[niner]

As far as I know, we have human plasma numbers from a 25mg study using humans, don't we? Wouldn't this be more helpful than BSA estimates?

We also have human plasma numbers from a dose ranging study that went up to 5g. And I would tend to agree that given the plasma numbers in mice, rats, and humans, we now have more to go on, and that changes the need to rely on the allometric scaling approximations. When you have nothing else to go on besides an oral dose and some sort of symptomatic endpoint, then allometric scaling is a great starting point that takes into account the many differences between species. But if you have blood levels for both species, you have eliminated questions about absorption, metabolism, and plasma volume. We still need to consider differences in volumes of tissue compartments and differences in binding at the target receptor. It seems reasonable to me that we should attempt to match the lowest blood levels that showed the results we are interested in, and that blood level information should override allometric scaling approximations. I'm open to arguments why this might not be the case though. Any thoughts?

[krillin]

Aromatase inhibitors may protect against prostate cancer but promote nasty (but reversible once the drug is stopped) joint problems.

Hmm. I guess resveratrol should be added to the list of autoimmune risk supplements like aminoguanidine and lipoic acid.

J Rheumatol. 2007 Oct 15
Joint Pain with Aromatase Inhibitors: Abnormal Frequency of Sjögren's Syndrome.
Laroche M, Borg S, Lassoued S, De Lafontan B, Roché H.
From the Service de Rhumatologie, CHU Rangueil; and the Service de Cancérologie, Institut Claudius Regaud, Toulouse, France.

OBJECTIVE: Since the results of the ATAC study, women who have undergone surgery for breast cancer and who require adjuvant hormone therapy are often treated with aromatase inhibitors. With these treatments, joint pain is frequent (30% to 40%) and quite often disabling (5% to 10%). Our objective was to investigate the origin of the pain induced by the anti-aromatases. METHODS: Twenty-four women of mean age 59 years with joint pain of > 5/10 on a visual analog scale underwent a rheumatological consultation and systematic laboratory tests. RESULTS: In 5 patients, pain was considered to have a well defined cause: osteoarthritis, shoulder tendinitis, or paraneoplastic aponeurositis. The other 19 patients had inflammatory pain of the fingers, wrists, shoulders, forefeet, ankles, or knees, with slight synovial thickening of the PIP and MCP joints. Two had an inflammatory syndrome on laboratory tests. Nine of these patients had antinuclear antibodies (ANA > 1/160 on HEp-2 cells) and 4 had rheumatoid factors (> 20 U). Ten patients had sicca syndrome of the eyes or mouth, 7 had probable Sjögren's syndrome according to the San Diego criteria, and one had definite Sjögren's syndrome. One had rheumatoid arthritis, one had Hashimoto thyroiditis, and 2 had positive hepatitis C serology. CONCLUSION: Is the almost total estrogen depletion induced by aromatase inhibitors conducive to the development of sicca syndromes with ANA? Our results should be considered in relation to the Sjögren-like syndromes occurring in aromatase knock-out mice as recently reported.

PMID: 17937464

Gastroenterology. 2003 Dec;125(6):1705-13.
Autoreactivity to lipoate and a conjugated form of lipoate in primary biliary cirrhosis.
Bruggraber SF, Leung PS, Amano K, Quan C, Kurth MJ, Nantz MH, Benson GD, Van de Water J, Luketic V, Roche TE, Ansari AA, Coppel RL, Gershwin ME.
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis Medical School, 95616, USA.

BACKGROUND & AIMS: Although considerable effort has been directed toward the mapping of peptide epitopes by autoantibodies, the role of nonprotein molecules has been less well studied. The immunodominant autoantigen in primary biliary cirrhosis (PBC), E2 components of pyruvate dehydrogenase complexes (PDC-E2), has a lipoate molecule bonded to the domain to which autoantibodies are directed. METHODS: We examined sera from patients with PBC (n = 105), primary sclerosing cholangitis (n = 70), and rheumatoid arthritis (n = 28) as well as healthy volunteers (n = 43) for reactivity against lipoic acid. The lipoic acid hapten specificity of the reactive antibodies in PBC sera was determined following incubation of aliquots of the sera with human serum albumin (HSA), lipoylated HSA (HSA-LA), PDC-E2, lipoylated PDC-E2, polyethylene glycol (PEG), lipoylated PEG, free lipoic acid, and synthetic molecular mimics of lipoic acid. RESULTS: Anti-lipoic acid specific antibodies were detected in 81% (79 of 97) of antimitochondrial antibody (AMA)-positive patients with PBC but not in controls. Two previously unreported specificities in AMA-positive sera that recognize free lipoic acid and a carrier-conjugated form of lipoic acid were also identified. CONCLUSIONS: We hypothesize that conjugated form(s) of native or xenobiotic lipoic acid mimics contribute to the initiation and perpetuation of autoimmunity by at first breaking self-tolerance and participating in subsequent determinant spreading. The variability in the immunoreactive carrier/lipoate conjugates provides an experimental framework on which potential mechanisms for the breakdown of self-tolerance following exposure to xenobiotics can be investigated. The data have implications for patients taking lipoic acid as a dietary supplement.

PMID: 14724823

http://www.medscape....ticle/460902_21

These are the summary results of the aminoguanidine (pimagedine) studies of diabetic nephropathy. A substantial number of patients with type 1 and type 2 diabetes with clinical nephropathy, proteinuria, and creatinine up to 2 mg/dL were studied at 2 different dose levels and compared with placebo.

The studies were troubled by issues with regards to safety, with flu-like syndrome being present in both type 1 and type 2 diabetes patients, and moderate anemia being an issue for another subset of patients. But most disturbing was a problem with elevated antinuclear antibodies and antineutrophil cytoplasm autoantibodies (ANCA) vasculitis, resulting in glomerulonephritis and stroke in a handful of patients.

[tintinet]

Anecdotally, during my recent bought of arthralgias, peripheral neuropathy, etc., I had a fairly thorough rheumatologic work up: ANA neg., CRP very low, FWIW.