Alpha lipoic acid (ALA) is an antioxidant found in vegetables and supplements believed to reduce cellular damage and restore vitamin C and vitamin E levels. It is approved in Germany for the treatment of Diabetes related peripheral neuropathy. It has also been used to treat eye diseases, fatigue, headache, memory problems, HIV infection, heart disease, and Lyme disease.
Sources of alpha lipoic acid (ALA):
Sources of ALA include broccoli, spinach, collard greens, citrus, rice bran, tomatoes, and potatoes.
Alpha lipoic acid (ALA) and pain:
ALA and neuropathic pain:
Research suggests that ALA reduces neuropathic pain related to peripheral neuropathy in patients with diabetes.
In a double-blind, placebo-controlled trial by Ziegler D et al, 181 people with diabetic peripheral neuropathy were given either placebo or one of 3 doses of lipoic acid: 600, 1200 or 1800 mg daily. Over the five week study period, benefits were seen in all three lipoic acid groups as compared to the placebo group. Average total symptom score (TSS) (including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet) improved by 51% in ALA600, 48% in ALA1200, and 52% in ALA1800 compared with just 32% in the placebo group. Rates for those experiencing a 50% or more reduction in TSS was 62% (ALA600), 50% (ALA1200), 56% (ALA1800), and 26% (placebo). Participants experienced increased symptoms of nausea, vomiting, and vertigo as the dose of ALA increased. (1)
A review of studies found that among diabetes patients with peripheral neuropathy, a problem with the nerves that can produce pain, loss of sensation, and an inability to control muscles, alpha lipoic acid was found to significantly reduce neuropathic pain. Alpha lipoic acid, a fatty acid, is also an antioxidant found naturally inside every cell in the body. It\’s needed by the body to produce the energy for the body\’s normal functions. Researches found that alpha lipoic acid was associated with an average total symptom scores reduction of 2.26. Specifically, when given orally the reduction was 1.78 and when administered by IV the reduction increased to 2.81. There is also evidence that alpha lipoic acid decreases neuropathic pain when given for a period of 3 weeks at a dose of 600 mg/day (grade of recommendation A). (2)
Participants in a study by Ametov AS et al were randomized to IV administration of either ALA (600 mg) (n = 60) or placebo (n = 60) for 5 days/week for a total of 14 treatments. At the end of the study, the total symptom score in patients taking ALA had improved by an average of 4.8 points, compared to an improvement of only 1.8 points in the placebo group. Compared to the placebo group, the treatment group had evidence of significant improvement in pain, asleep numbness and prickling neuropathy signs, which is an overall measure of effectiveness. (3)
A meta-analysis by Han T et al of 15 randomized controlled trials found that IV administration of 300-600 mg/day α-lipoic acid (ALA) for 2-4 weeks for treatment of diabetic peripheral neuropathy (DPN), a problem with the nerves that can produce pain, loss of sensation, and an inability to control muscles, was associated with a significant improvement in nerve conduction velocity and neuropathic symptoms. ALA was associated with an average benefit for median motor nerve conduction velocity (MNCV) of 4.63, median sensory nerve conduction velocity (SNCV) of 3.17, for peroneal MNCV, 4.25, and 3.65 for peroneal SNCV. (4)
Alpha lipoic acid (ALA) and diabetes:
Alpha lipoic acid (ALA) may benefit diabetes patients by improving insulin sensitivity. A small trial of oral ALA was found to increase insulin sensitivity in people with type 2 diabetes. Researchers treated 24 patients over four weeks with either 600 mg twice daily of ALA (n=12) or placebo (n=12). At the end of the study, the insulin sensitivity (Is) of the diabetics was significantly improved (M from 3.202 to 5.95 mg/kg/min, Is from 4.706 to 7.673 mg/kg/min per mIU/l x 100). The difference was not statistically significant between the treated patients and the placebo group after the end of the period. (5)
Alpha lipoic acid (ALA), cardiovascular disease risk, and end stage renal disease:
Alpha lipoic acid (ALA) may improve cardiovascular risk in patients with end stage renal disease on hemodialysis (HD). In a study by Chang et al, ALA reduce asymmetric dimethylarginine (ADMA), a naturally occurring chemical found in blood that stops the production of nitric oxide (NO). ADMA is considered a cardiovascular risk factor in diabetic patients with end stage renal disease on HD. Patients (n=53) on HD 3 times a week were randomized to either ALA 600 mg/day for 12 weeks or placebo. At the end of the study, the ALA group experienced a significant reduction in blood levels of ADMA from a median of 1.68 micromoles to 1.31 micromoles. Patients in the placebo group had no change in ADMA, levels of total cholesterol, serum albumin, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, or hemoglobin A1C. (6)
Alpha lipoic acid (ALA) and skin health:
An oral nutritional supplement for the skin containing alpha lipoic acid (ALA) improved skin thickness and elasticity. A randomized, double-blind, placebo-controlled study by Thom E et al evaluated 40 female subjects over 6-months after taking an oral treatment named DermaVite. The supplement contained a marine protein, alpha-lipoic acid, lycopene, pine-bark extract and vitamins and minerals and was developed for treatment of aging symptoms of the skin. Half of the participants (n=20) received DermaVite while 20 received placebo. The results show a significant improvement in skin quality (skin thickness and elasticity). The participants\’ self-evaluation showed a statistical difference in favor of the active treatment.
Alpha lipoic acid (ALA) and Alzheimer’s disease:
Alpha lipoic acid (ALA) stabilized cognitive function and lowered progression of Alzheimer\’s disease in a study by Hager K et al. However, this was not a double-blinded, placebo-controlled or randomized design. Because oxidative stress is an important contributor to Alzheimer\’s disease, powerful antioxidants like alpha lipoic acid (ALA) may help to slow down its progression in people already diagnosed with Alzheimer\’s. One study found that alpha lipoic acid protects against Alzheimer\’s by preventing free radical production. In one study, a daily dose of 600 mg of ALA was given to 9 patients with Alzheimer\’s disease and after a year, the ALA helped to stabilize their cognitive function as measured by two neuropsychological tests (the mini mental state exam, MMSE and the Alzheimer\’s disease assessment score cognitive subscale, ADAS cog). During a larger and longer follow-up study that included 43 patients observed for up to 48 months, the progression of the disease was dramatically lower among those taking ALA compared to those getting no treatment or those taking conventional Alzheimer drugs. In patients with mild dementia ADAS cog increased by 1.2 points/year and MMSE decreased by 0.6 points/year. The results were about twice these rates in patients with moderate dementia. (8)
Alpha Lipoic Acid (ALA) Adverse Reactions and Interactions:
Participants in the study by Ziegler D et al experienced increasing symptoms of nausea, vomiting, and vertigo as the dose of ALA was increased from 600 mg to 1200 mg to 1800 mg per day.
Assessment and Plan: Alpha Lipoic Acid
- An Alpha lipoic acid (ALA) supplement under a physician’s direction may be an option to treat peripheral neuropathy in diabetes patients. A dose of 600 mg oral once per day was given over 5 weeks and provides the best risk to benefit ratio given side effects according to the study by Ziegler D et al (1). ALA has not been studied long term. Nausea, vomiting, and vertigo occurred as the dose of ALA was increased from 600 mg to 1200 mg to 1800 mg per day (1). Intravenous ALA is available and may be effective but is not practical given cost and ability to treat with oral treatment.
- Alpha lipoic acid levels necessary for treatment of peripheral neuropathy are not possible with intake of ALA from food sources. Alpha lipoic acid (ALA) containing foods include broccoli, spinach, collard greens, citrus, rice bran, tomatoes, and potatoes.
- More research is required before ALA supplements can be recommended for improving insulin sensitivity, treating Alzheimer’s disease or to treat signs of skin aging.
References:
1.Ziegler D, Ametov A, Barinov A, et al. Oral Treatment With alpha-lipoic Acid Improves Symptomatic Diabetic Polyneuropathy: The SYDNEY 2 trial. Diabetes Care . 2006;29:2365-2370. http://care.diabetesjournals.org/content/29/11/2365.abstract
2.Ametov AS, Barinov A, Dyck PJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 2003;26:770-776. http://www.ncbi.nlm.nih.gov/pubmed/12610036
3.Mijnhout GS, Kollen BJ, Alkhalaf A, Kleefstra N, Bilo HJ. Alpha lipoic Acid for symptomatic peripheral neuropathy in patients with diabetes: a meta-analysis of randomized controlled trials. Int J Endocrinol. 2012;2012:456279. http://www.ncbi.nlm.nih.gov/pubmed/22331979
4.Han T, Bai J, Liu W, Hu Y. A systematic review and meta-analysis of α-lipoic acid in the treatment of diabetic peripheral neuropathy. Eur J Endocrinol. 2012 Oct;167(4):465-71. http://www.ncbi.nlm.nih.gov/pubmed/22837391
5.Kamenova P. Improvement of insulin sensitivity in patients with type 2 diabetes mellitus after oral administration of alpha-lipoic acid. Hormones (Athens). Oct-Dec 2006;5(4):251-258. http://www.ncbi.nlm.nih.gov/pubmed/17178700
6.Chang, J. W., Lee, E. K., Kim, T. H., et al. Effects of alpha-lipoic acid on the plasma levels of asymmetric dimethylarginine in diabetic end-stage renal disease patients on hemodialysis: a pilot study. Am. J. Nephrol. 2007; 27, 70–74. http://www.ncbi.nlm.nih.gov/pubmed/17259696
7.Thom E. A randomized, double-blind, placebo-controlled study on the clinical efficacy of oral treatment with DermaVite on ageing symptoms of the skin. J Int Med Res. 2005 May-Jun;33(3):267-72. http://www.ncbi.nlm.nih.gov/pubmed/15938587
8.Hager K, Kenklies M, McAfoose J, Engel J, Münch G. Alpha-lipoic acid as a new treatment option for Alzheimer\’s disease–a 48 months follow-up analysis. J Neural Transm Suppl. 2007;(72):189-93. http://www.ncbi.nlm.nih.gov/pubmed/17982894