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LONDON—Daily oral intake of 1,200 mg of racemic lipoic acid significantly reduces the rate of whole brain atrophy among patients with secondary progressive multiple sclerosis (MS), according to data described at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS). Overall, lipoic acid is safe and well tolerated.
“These results need further exploration in a larger sample size to clarify the effect size of lipoic acid, to determine the clinical benefits associated with reduction in brain atrophy, and to explore the mechanisms of action of lipoic acid in progressive MS,” said Rebecca Spain, MD, MSPH, neurologist at the VA Portland Health Care System and Oregon Health & Science University in Portland. 
An Antioxidant With Many Roles
Lipoic acid is a small-molecule antioxidant with several biologic functions, such as participating in oxidative respiration in mitochondria, influencing endothelial cell function, and inhibiting inappropriate microglial activation. A synthetic version of the antioxidant is available commercially at low cost.
Several studies have indicated that lipoic acid reduces disability in mice with experimental autoimmune encephalomyelitis. Based on those results, Dr. Spain and colleagues conducted a two-year, double-blind trial in which patients with secondary progressive MS were randomized in equal groups to 1,200 mg/day of oral racemic lipoic acid or placebo. Participants underwent yearly MRI. The investigators’ primary outcome was the annualized percent change in brain volume, as measured by structural image evaluation, using normalization of atrophy (SIENA). They also sought to compare changes in disability and quality of life between the two groups and to assess the safety and tolerability of lipoic acid.
In their intention-to-treat analysis, the researchers used a linear mixed model approach to evaluate the effects of lipoic acid on annualized rates of change in outcomes. They corrected the models for age, sex, and disease duration.
In all, 54 patients were randomized, and three withdrew before receiving treatment. The intention-to-treat placebo cohort included 24 patients, and the lipoic-acid cohort had 27 patients. Five participants, all in the lipoic-acid cohort, dropped out of the study. One person had claustrophobia and could not tolerate the MRI. Another participant had nausea and vomiting that subsided on discontinuation of lipoic acid. The third dropout had a new diagnosis of prostate cancer. The fourth had new proteinuria, and the fifth had worsening renal function.
The study population was representative of people with secondary progressive MS, albeit with greater disability. Mean age was 60, and average disease duration was 30 years. The treatment arms were well matched at baseline.
Trend Toward Improved Walking
The annualized rate of brain atrophy was 0.65% for the placebo group, “which is comparable to [that of] other progressive MS natural history cohorts,” said Dr. Spain. Among patients receiving lipoic acid, the annualized rate of brain atrophy was 0.22%, which was significantly different from that of the placebo cohort. “This represents a 66% reduction in the rate of brain atrophy in the lipoic-acid cohort, compared with placebo,” said Dr. Spain.
No other outcomes were significantly different between groups at 96 weeks. Performance on the Timed 25-Foot Walk test, however, tended to improve by approximately 12% (ie, from 8 seconds to 7 seconds) among participants receiving lipoic acid.
Gastrointestinal upset was significantly more common among participants receiving lipoic acid, as would be expected because of previous studies. New-onset proteinuria and worsening renal function were observed in the lipoic-acid cohort, but a consulting nephrologist did not consider either adverse event to be related to treatment. Unexpectedly, the investigators observed half as many falls in the lipoic acid arm, compared with controls.
The US Department of Veterans Affairs and the NIH supported this research. Pure Encapsulations provided the lipoic acid and placebo.
—Erik Greb
Suggested Reading
Chaudhary P, Marracci G, Galipeau D, et al. Lipoic acid reduces inflammation in a mouse focal cortical experimental autoimmune encephalomyelitis model. J Neuroimmunol. 2015;289:68-74.
Plemel JR, Juzwik CA, Benson CA, et al. Over-the-counter anti-oxidant therapies for use in multiple sclerosis: A systematic review. Mult Scler. 2015;21(12):1485-1495.
Yadav V, Marracci G, Lovera J, et al. Lipoic acid in multiple sclerosis: a pilot study. Mult Scler. 2005;11(2):159-165.
LONDON—Daily oral intake of 1,200 mg of racemic lipoic acid significantly reduces the rate of whole brain atrophy among patients with secondary progressive multiple sclerosis (MS), according to data described at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS). Overall, lipoic acid is safe and well tolerated.
“These results need further exploration in a larger sample size to clarify the effect size of lipoic acid, to determine the clinical benefits associated with reduction in brain atrophy, and to explore the mechanisms of action of lipoic acid in progressive MS,” said Rebecca Spain, MD, MSPH, neurologist at the VA Portland Health Care System and Oregon Health & Science University in Portland.
An Antioxidant With Many Roles
Lipoic acid is a small-molecule antioxidant with several biologic functions, such as participating in oxidative respiration in mitochondria, influencing endothelial cell function, and inhibiting inappropriate microglial activation. A synthetic version of the antioxidant is available commercially at low cost.
Several studies have indicated that lipoic acid reduces disability in mice with experimental autoimmune encephalomyelitis. Based on those results, Dr. Spain and colleagues conducted a two-year, double-blind trial in which patients with secondary progressive MS were randomized in equal groups to 1,200 mg/day of oral racemic lipoic acid or placebo. Participants underwent yearly MRI. The investigators’ primary outcome was the annualized percent change in brain volume, as measured by structural image evaluation, using normalization of atrophy (SIENA). They also sought to compare changes in disability and quality of life between the two groups and to assess the safety and tolerability of lipoic acid.
In their intention-to-treat analysis, the researchers used a linear mixed model approach to evaluate the effects of lipoic acid on annualized rates of change in outcomes. They corrected the models for age, sex, and disease duration.
In all, 54 patients were randomized, and three withdrew before receiving treatment. The intention-to-treat placebo cohort included 24 patients, and the lipoic-acid cohort had 27 patients. Five participants, all in the lipoic-acid cohort, dropped out of the study. One person had claustrophobia and could not tolerate the MRI. Another participant had nausea and vomiting that subsided on discontinuation of lipoic acid. The third dropout had a new diagnosis of prostate cancer. The fourth had new proteinuria, and the fifth had worsening renal function.
The study population was representative of people with secondary progressive MS, albeit with greater disability. Mean age was 60, and average disease duration was 30 years. The treatment arms were well matched at baseline.
Trend Toward Improved Walking
The annualized rate of brain atrophy was 0.65% for the placebo group, “which is comparable to [that of] other progressive MS natural history cohorts,” said Dr. Spain. Among patients receiving lipoic acid, the annualized rate of brain atrophy was 0.22%, which was significantly different from that of the placebo cohort. “This represents a 66% reduction in the rate of brain atrophy in the lipoic-acid cohort, compared with placebo,” said Dr. Spain.
No other outcomes were significantly different between groups at 96 weeks. Performance on the Timed 25-Foot Walk test, however, tended to improve by approximately 12% (ie, from 8 seconds to 7 seconds) among participants receiving lipoic acid.
Gastrointestinal upset was significantly more common among participants receiving lipoic acid, as would be expected because of previous studies. New-onset proteinuria and worsening renal function were observed in the lipoic-acid cohort, but a consulting nephrologist did not consider either adverse event to be related to treatment. Unexpectedly, the investigators observed half as many falls in the lipoic acid arm, compared with controls.
The US Department of Veterans Affairs and the NIH supported this research. Pure Encapsulations provided the lipoic acid and placebo.
—Erik Greb
Suggested Reading
Chaudhary P, Marracci G, Galipeau D, et al. Lipoic acid reduces inflammation in a mouse focal cortical experimental autoimmune encephalomyelitis model. J Neuroimmunol. 2015;289:68-74.
Plemel JR, Juzwik CA, Benson CA, et al. Over-the-counter anti-oxidant therapies for use in multiple sclerosis: A systematic review. Mult Scler. 2015;21(12):1485-1495.
Yadav V, Marracci G, Lovera J, et al. Lipoic acid in multiple sclerosis: a pilot study. Mult Scler. 2005;11(2):159-165.
LONDON—Daily oral intake of 1,200 mg of racemic lipoic acid significantly reduces the rate of whole brain atrophy among patients with secondary progressive multiple sclerosis (MS), according to data described at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS). Overall, lipoic acid is safe and well tolerated.
“These results need further exploration in a larger sample size to clarify the effect size of lipoic acid, to determine the clinical benefits associated with reduction in brain atrophy, and to explore the mechanisms of action of lipoic acid in progressive MS,” said Rebecca Spain, MD, MSPH, neurologist at the VA Portland Health Care System and Oregon Health & Science University in Portland.
An Antioxidant With Many Roles
Lipoic acid is a small-molecule antioxidant with several biologic functions, such as participating in oxidative respiration in mitochondria, influencing endothelial cell function, and inhibiting inappropriate microglial activation. A synthetic version of the antioxidant is available commercially at low cost.
Several studies have indicated that lipoic acid reduces disability in mice with experimental autoimmune encephalomyelitis. Based on those results, Dr. Spain and colleagues conducted a two-year, double-blind trial in which patients with secondary progressive MS were randomized in equal groups to 1,200 mg/day of oral racemic lipoic acid or placebo. Participants underwent yearly MRI. The investigators’ primary outcome was the annualized percent change in brain volume, as measured by structural image evaluation, using normalization of atrophy (SIENA). They also sought to compare changes in disability and quality of life between the two groups and to assess the safety and tolerability of lipoic acid.
In their intention-to-treat analysis, the researchers used a linear mixed model approach to evaluate the effects of lipoic acid on annualized rates of change in outcomes. They corrected the models for age, sex, and disease duration.
In all, 54 patients were randomized, and three withdrew before receiving treatment. The intention-to-treat placebo cohort included 24 patients, and the lipoic-acid cohort had 27 patients. Five participants, all in the lipoic-acid cohort, dropped out of the study. One person had claustrophobia and could not tolerate the MRI. Another participant had nausea and vomiting that subsided on discontinuation of lipoic acid. The third dropout had a new diagnosis of prostate cancer. The fourth had new proteinuria, and the fifth had worsening renal function.
The study population was representative of people with secondary progressive MS, albeit with greater disability. Mean age was 60, and average disease duration was 30 years. The treatment arms were well matched at baseline.
Trend Toward Improved Walking
The annualized rate of brain atrophy was 0.65% for the placebo group, “which is comparable to [that of] other progressive MS natural history cohorts,” said Dr. Spain. Among patients receiving lipoic acid, the annualized rate of brain atrophy was 0.22%, which was significantly different from that of the placebo cohort. “This represents a 66% reduction in the rate of brain atrophy in the lipoic-acid cohort, compared with placebo,” said Dr. Spain.
No other outcomes were significantly different between groups at 96 weeks. Performance on the Timed 25-Foot Walk test, however, tended to improve by approximately 12% (ie, from 8 seconds to 7 seconds) among participants receiving lipoic acid.
Gastrointestinal upset was significantly more common among participants receiving lipoic acid, as would be expected because of previous studies. New-onset proteinuria and worsening renal function were observed in the lipoic-acid cohort, but a consulting nephrologist did not consider either adverse event to be related to treatment. Unexpectedly, the investigators observed half as many falls in the lipoic acid arm, compared with controls.
The US Department of Veterans Affairs and the NIH supported this research. Pure Encapsulations provided the lipoic acid and placebo.
—Erik Greb
Suggested Reading
Chaudhary P, Marracci G, Galipeau D, et al. Lipoic acid reduces inflammation in a mouse focal cortical experimental autoimmune encephalomyelitis model. J Neuroimmunol. 2015;289:68-74.
Plemel JR, Juzwik CA, Benson CA, et al. Over-the-counter anti-oxidant therapies for use in multiple sclerosis: A systematic review. Mult Scler. 2015;21(12):1485-1495.
Yadav V, Marracci G, Lovera J, et al. Lipoic acid in multiple sclerosis: a pilot study. Mult Scler. 2005;11(2):159-165.
