Lipoic acid reduces the rate of brain atrophy in SPMS...

[MSUK]

Lipoic acid reduces the rate of brain atrophy in SPMS patients

In a study that set out to determine whether lipoic acid slowed the whole-brain atrophy rate in people with secondary progressive multiple sclerosis (SPMS), scientists discovered a 68% reduction in annualised percent change brain volume (PCBV). This suggests a clinical benefit in SPMS, while maintaining favourable safety, tolerability, and compliance over a two year period...Read more - http://www.ms-uk.org/lipoic-acid-reduce ... nts-030717

Edited 04/07/17. Sorry for the error.

[NHE]

Lipoic acid reduces the rate of brain atrophy in SPMS patients

In a study that set out to determine whether lipoic acid slowed the whole-brain atrophy rate in people with secondary progressive multiple sclerosis (SPMS), scientists discovered a 68% reduction in annualised perfused cerebral blood volume (PCBV). This suggests a clinical benefit in SPMS, while maintaining favourable safety, tolerability, and compliance over a two year period...Read more - http://www.ms-uk.org/lipoic-acid-reduce ... nts-030717

Unfortunately, there appears to be an error in the article. PCBV stands for percent change brain volume, not perfused cerebral blood volume. So, there was a 68% reduction in the loss of brain volume (atrophy) which makes more sense.

Here's the abstract with a link to the free full text article.

Lipoic acid in secondary progressive MS. A randomized controlled pilot trial.
Neurol Neuroimmunol Neuroinflamm September 2017 vol. 4 no. 5 e374

Objective: To determine whether lipoic acid (LA), an endogenously produced antioxidant, slowed the whole-brain atrophy rate and was safe in secondary progressive MS (SPMS).

Methods: Patients with SPMS aged 40–70 years enrolled in a single center, 2-year, double-blind, randomized trial of daily oral 1,200 mg LA vs placebo. Primary outcome was change in annualized percent change brain volume (PCBV). Secondary outcomes were changes in rates of atrophy of segmented brain, spinal cord, and retinal substructures, disability, quality of life, and safety. Intention-to-treat analysis used linear mixed models.

Results: Participation occurred between May 2, 2011, and August 14, 2015. Study arms of LA (n = 27) and placebo (n = 24) were matched with mean age of 58.5 (SD 5.9) years, 61% women, mean disease duration of 29.6 (SD 9.5) years, and median Expanded Disability Status Score of 6.0 (interquartile range 1.75). After 2 years, the annualized PCBV was significantly less in the LA arm compared with placebo (−0.21 [standard error of the coefficient estimate (SEE) 0.14] vs −0.65 [SEE 0.10], 95% confidence interval [CI] 0.157–0.727, p = 0.002). Improved Timed 25-Foot Walk was almost but not significantly better in the LA than in the control group (−0.535 [SEE 0.358] vs 0.137 [SEE 0.247], 95% CI −1.37 to 0.03, p = 0.06). Significantly more gastrointestinal upset and fewer falls occurred in LA patients. Unexpected renal failure (n = 1) and glomerulonephritis (n = 1) occurred in the LA cohort. Compliance, measured by pill counts, was 87%.

Conclusions: LA demonstrated a 68% reduction in annualized PCBV and suggested a clinical benefit in SPMS while maintaining favorable safety, tolerability, and compliance over 2 years.

[euphoniaa]

Lipoic acid reduces the rate of brain atrophy in SPMS patients

In a study that set out to determine whether lipoic acid slowed the whole-brain atrophy rate in people with secondary progressive multiple sclerosis (SPMS), scientists discovered a 68% reduction in annualised perfused cerebral blood volume (PCBV). This suggests a clinical benefit in SPMS, while maintaining favourable safety, tolerability, and compliance over a two year period...Read more - http://www.ms-uk.org/lipoic-acid-reduce ... nts-030717

Unfortunately, there appears to be an error in the article. PCBV stands for percent change brain volume, not perfused cerebral blood volume. So, there was a 68% reduction in the loss of brain volume (atrophy) which makes more sense.

Here's the abstract with a link to the free full text article.

Lipoic acid in secondary progressive MS. A randomized controlled pilot trial.
Neurol Neuroimmunol Neuroinflamm September 2017 vol. 4 no. 5 e374

Wow, thanks, NHE, for the correction.

Interesting study, however, besides the gastrointestinal problems, I'm a bit concerned about this quote from the article:

The suggestion of greater increase in T2-lesion volume in the LA cohort is of uncertain significance. The increase may be real and thus represent potential harmful effects of LA, may represent physiologic changes other than due to MS, may result from MR postprocessing quality issues, or may not be different from placebo.15 Further evaluation is warranted.

[NHE]

What has me shaking my head and asking WTF? is that they used racemic lipoic acid. This is a 50/50 mix of the R and S isomers also known as enantiomers. The R enantiomer is the natural form found in our bodies. The S form is a product of chemical synthesis and has some negative physiological effects. It's best to use a stabilized form of R-lipoic acid. Please see the following discussion topic for more information. It's possible that the negative side effects seen in the study were due to the S enantiomer of lipoic acid.

http://www.thisisms.com/forum/natural-a ... c4347.html

This is one of my old posts from 10 years ago. The paper by Lester Packer et al. It is nearly 16 years old. The data on the negative effects from S-lipoic acid have been known for a while now. So I repeat, "Racemic lipoic acid? WTF?"

[frodo]

What has me shaking my head and asking WTF? is that they used racemic lipoic acid. This is a 50/50 mix of the R and S isomers also known as enantiomers. The R enantiomer is the natural form found in our bodies. The S form is a product of chemical synthesis and has some negative physiological effects.

Thanks for the analysis. Probably they did the trial trying to introduce the synthetic form. They cannot charge too much for the other. At least the study has been made.

[NHE]

What has me shaking my head and asking WTF? is that they used racemic lipoic acid. This is a 50/50 mix of the R and S isomers also known as enantiomers. The R enantiomer is the natural form found in our bodies. The S form is a product of chemical synthesis and has some negative physiological effects.

Thanks for the analysis. Probably they did the trial trying to introduce the synthetic form. They cannot charge too much for the other. At least the study has been made.

Here is the statement from the paper's methods section.

Investigational drug. An Investigational New Drug indication was obtained by the PI (no. 110132). Pure Encapsulations (Sudbury, MA) provided gelatin capsules containing 600 mg racemic LA or placebo. Placebo capsules contained Avicel (microcellulose crystal) and 4.3 mg of quercetin (a bioflavonoid) that rendered the placebo a yellow color, similar to LA. Expiration of the study drug was extended once during the study by Pure Encapsulations after retesting of sample capsules determined continued stability.

There are a couple of things one should notice here. 1. They used racemic lipoic acid (as previously discussed). 2. It was provided by a company called Pure Encapsulations. This is a standard supplement supplier that already sells lipoic acid to the public. The stuff is reasonably priced and inexpensive compared to MS drugs. Vitacost sells a 60 ct. bottle for $52. That's considerably less than a month's worth of any of the MS DMDs. Moreover, R-lipoic acid has 6-12 x greater efficacy. Stabilized R-lipoic acid from Dr's Best is $31.79 for 60 ct. of 200 mg tablets. This should be equivalent to 1200 mg of the racemic form. This makes Dr's Best 31% of the cost of Pure Encapsulations and it's better since there's no S-lipoic acid present. Lastly, 3. Their "placebo" contained quercetin. Granted, 4.3 mg quercetin appears to be a low dose, but it may not be biologically neutral as the following two papers suggest.

Quercetin, a flavonoid phytoestrogen, ameliorates experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK-STAT pathway in T lymphocyte.
J Clin Immunol. 2004 Sep;24(5):542-52.

Experimental allergic encephalomyelitis (EAE) is a Th1 cell-mediated inflammatory demyelinating autoimmune disease model of multiple sclerosis (MS). Quercetin (3,3'4',5,7-pentahydroxy flavone) is a flavonoid phytoestrogen that has profound anticancer and anti-inflammatory activities. In this study, we show that in vivo treatment of SJL/J mice with quercetin (i.p. 50 or 100 microg every other day) ameliorates EAE in association with the inhibition of IL-12 production and neural antigen-specific Th1 differentiation. In vitro treatment of activated T cells with quercetin blocks IL-12-induced tyrosine phosphorylation of JAK2, TYK2, STAT3, and STAT4, resulting in a decrease in IL-12-induced T cell proliferation and Th1 differentiation. These findings highlight the fact that quercetin ameliorates EAE by blocking IL-12 signaling and Th1 differentiation and suggest its use in the treatment of MS and other Th1 cell-mediated autoimmune diseases.Demyelination is a characteristic hallmark of the neuro-inflammatory disease multiple sclerosis. During demyelination, macrophages phagocytose myelin and secrete inflammatory mediators that worsen the disease. Here, we investigated whether flavonoids, naturally occurring immunomodulating compounds, are able to influence myelin phagocytosis by macrophages in vitro. The flavonoids luteolin, quercetin and fisetin most significantly decreased the amount of myelin phagocytosed by a macrophage cell line without affecting its viability. IC(50) values for these compounds ranged from 20 to 80 microM. The flavonoid structure appeared to be essential for observed effects as flavonoids containing hydroxyl groups at the B-3 and B-4 positions in combination with a C-2,3 double bond were most effective. The capacity of the various flavonoids to inhibit phagocytosis correlated well with their potency as antioxidant, which is in line with the requirement of reactive oxygen species for the phagocytosis of myelin by macrophages. Our results implicate that flavonoids may be able to limit the demyelination process during multiple sclerosis.


Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study.
Biochem Pharmacol. 2003 Mar 1;65(5):877-85.

Demyelination is a characteristic hallmark of the neuro-inflammatory disease multiple sclerosis. During demyelination, macrophages phagocytose myelin and secrete inflammatory mediators that worsen the disease. Here, we investigated whether flavonoids, naturally occurring immunomodulating compounds, are able to influence myelin phagocytosis by macrophages in vitro. The flavonoids luteolin, quercetin and fisetin most significantly decreased the amount of myelin phagocytosed by a macrophage cell line without affecting its viability. IC(50) values for these compounds ranged from 20 to 80 microM. The flavonoid structure appeared to be essential for observed effects as flavonoids containing hydroxyl groups at the B-3 and B-4 positions in combination with a C-2,3 double bond were most effective. The capacity of the various flavonoids to inhibit phagocytosis correlated well with their potency as antioxidant, which is in line with the requirement of reactive oxygen species for the phagocytosis of myelin by macrophages. Our results implicate that flavonoids may be able to limit the demyelination process during multiple sclerosis.