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Alpha Lipoic Acid Question

January 4, 2013 Written by JP    [Font too small?]

Today’s column is a response to the first health related question that was posed to me in 2013. During a recent consultation, a client inquired about the relative merits of an antioxidant compound commonly known as alpha lipoic acid. She noted that it’s frequently cited as one of the more potent antioxidants because it supposedly works in concert with other free radical scavengers such as glutathione and vitamins C and E. A recent review in Frontiers in Ethnopharmacology, a prestigious medical journal, supports this claim and details various others functions of a-lipoic acid including its ability to: a) chelate heavy metals; b) lower systemic inflammation; c) regulate gene expression; d) repair damaged proteins in the body.

By far, the most prevalent application of a-lipoic acid is in the field of integrative diabetic care. In recent months, several new studies and a systematic review report that alpha lipoic acid is an effective means of managing diabetes and related complications. For instance, the October 2012 issue of the European Journal of Endocrinology analyzed the results of fifteen randomized controlled trials on the effects of intravenous a-lipoic acid in patients with diabetic peripheral neuropathy – a common form of nerve damage that can cause numbness and pain. The findings of the meta-analysis determined that alpha lipoic acid, “is safe and that the treatment can significantly improve both nerve conduction velocity and positive neuropathic symptoms”. Other recent studies report that the use of a-lipoic acid also imparts potent antioxidant activity in both type 1 and type 2 diabetics, and may have an additional application for diabetics and non-diabetics at risk for cardiovascular disease. One interesting finding buried deep in the medical literature is that a combination of aerobic exercise and a-lipoic acid may yield greater health benefits than either practice alone.

In closing, I want to point out a few important details about a-lipoic acid and its potential as a dietary supplement. First, while many foods including broccoli, liver and spinach contain alpha lipoic acid, they don’t possess enough of it to serve in a therapeutic capacity. Second, two studies from 2012 suggest that a-lipoic acid may be a valuable adjunct for select eye conditions such as age-related macular degeneration and dry eye syndrome. In the case of dry eye syndrome, a nutraceutical consisting of a-lipoic acid, EPA (a fatty acid found in fish oil) and phytoestrogens “significantly improved signs and symptoms of dry eye syndrome” in a group of postmenopausal women. Last, but not least, is the issue of dosage and form. The two most common forms of a-lipoic acid are the natural version (R-alpha lipoic acid) and a mixture of the natural and a synthetic form of a-lipoic acid (R,S alpha lipoic acid). The natural R- form is more expensive and less studied, but appears to be more effective in certain individuals. The most common dosage utilized in current and previous clinical studies is approximately 600 mg/day of either intravenous or oral a-alpha lipoic acid. Ideally, oral versions of alpha lipoic acid should be split up due to its brief “half life” or length of activity after ingestion.

Note: Please check out the “Comments & Updates” section of this blog – at the bottom of the page. You can find the latest research about this topic there!

To learn more about the studies referenced in today’s column, please click on the following links:

Study 1 – A Systematic Review and Meta-Analysis of A-Lipoic Acid (link)

Study 2 – Comparative Study of Alpha-Lipoic Acid and Mexidol Effects (link)

Study 3 – Effect of A-Lipoic Acid on Platelet Reactivity in Type 1 Diabetic (link)

Study 4 – Alpha-Lipoic Acid Ameliorates Oxidative Stress by Increasing Aldehyde (link)

Study 5 – Glycemic and Oxidative Status of Patients w/ Type 2 Diabetes (link)

Study 6 – Effect of A-Lipoic Acid and Exercise Training on Cardiovascular Disease (link)

Study 7 – Effect of (R)-α-Lipoic Acid Supplementation on Serum Lipids (link)

Study 8 – Effects of Phytoestrogen Supplementation in Postmenopausal Women (link)

Study 9 – Age and Gender Dependent Bioavailability of R- and R,S-α-Lipoic Acid (link)

Study 10 – Single Dose Bioavailability and Pharmacokinetic Study of a Innovative (link)

Health Benefits Associated with Alpha Lipoic Acid

Source: Front. Pharmacol., 17 November 2011 (link)

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Posted in Diabetes, Heart Health, Nutritional Supplements

20 Comments & Updates to “Alpha Lipoic Acid Question”

  1. Iggy Dalrymple Says:

    Dr Berkson, formerly with the NIH, is a big believer in alpha lipoic acid.

  2. JP Says:

    Thanks for sharing that Iggy. Interesting! I should write a column about naltrexone in the near future as well.

    Be well and happy new year!


  3. liverock Says:

    Whilst ALA has shown many health benefits some research has shown that whilst it is sometimes quoted as being a heavy metal chelator for cadmium and mercury it can end up not removing the metal, but moving it around the body and depositing it in the brain.

    Thorne did a comprehensive study on Glutathione and ALC on their respective chelating effects of mercury and found in their conclusions that:

    “The evidence that ALA may mobilize
    heavy metals to other tissues from tissues where
    the metals are most concentrated, specifically the
    brain, is troublesome.”


    Dr Andrew Cutler will only use very small doses of 25mg of ALA for helping to remove mercury from his autistic patients for this reason.

    Obviously not all people will have this problem as ALA has shown to help the aging brain among some seniors, it probably depends on how well your natural cellular glutathione levels cope with heavy metals. If you are not blessed with adequate detoxing genes as well asliver,gall bladder and kidney functions, then you may well end up with a lot of circulating metals which ALA may dump in the brain.

  4. JP Says:

    Hi Liverock,

    Thank you for contributing this intriguing information! After reading your comment, I dug around a little and found this provocative study:


    In essence, it reports that alpha lipoic acid + Vitamins C & E appear to reduce oxidative stress in the cerebrospinal fluid of patients with Alzheimer’s disease. However, taking a combination of these antioxidants *may* actually hasten cognitive decline! Not good – *if* this unexpected finding is supported by other research.

    Based on your comment and the study described above, I’ll attempt to gather some additional data from a few a-lipoic acid experts that I’m familiar with. Please stay tuned!

    PS – Until then, here is a relevant study in an animal model of mercury exposure:


    Be well!


  5. liverock Says:

    It might have been better if the ALA had been combined with Selenium instead of Vitamins C&E.Selenium appears to be quite effective at binding Hg.



    A study by the Catholic University of Rome showed the hearts of advanced CHF patients had mercury levels 22,000 times higher than other body tissues. As this appears to be a widespread problem, it might be advisable for those with CHF to discuss with a health provider before starting to take large doses of ALA.


  6. JP Says:

    Thank you, Liverock.

    I agree that selenium can be useful re: reducing mercury accumulation. IMO, the role of mercury and cardiovascular disease is less certain. I’ll post some contradictory studies below. Naturally, I think it’s wise to limit mercury exposure and, when done judiciously and safely, lowering mercury-burden. I just don’t know if a-lipoic acid is likely to affect cardiovascular health in an adverse manner. Also, it’s important to consider whether the pros outweigh the cons.

    I’ll add this concern to my list of questions for the alpha lipoic acid experts I plan to contact.




    Be well!


  7. r.n Says:

    i find your site by searching(crime and nutrition).
    my Thesis is about nutrition and crime from the perspective of criminology.
    may you please help me.in my country Researches about this subject is too fiddling.
    thank you

  8. JP Says:

    Good day, r.n.

    You can find more information by clicking on the citations (links) that I included in my column entitled, “Crime and Nutrition”.


    You can also access additional research by visiting this medical journal database: http://www.ncbi.nlm.nih.gov/pubmed

    Be well!


  9. Michael Snyder Says:

    Hi! I’m 53, looked healthy and had no health issues or symptoms but was diagnosed with Stage 3A colon cancer. I had surgery and subsequent 6 months of Chemo with Fluorouracil and Oxaliplatin. Now (four months post chemo) I have (terrible) Peripheral Neuropathy. I have a comment and a question. Upon reading many websites, I find yours is just wonderful and thank you for your Curcumin (Oxaliplatin) article at https://www.healthyfellow.com/1406/best-curcumin-supplement. As a comment on Alpha Lipoic Acid, it is an ingredient in “Neuropathy Support Formula” which has been helping me. I took it for a month and I had areas of my arms and feet which have returned to normal. I then stopped taking it for a month and I quit experiencing improvement. I wanted to know if it was helping. I started taking it again and now new areas have returned to normal. My question is, are the levels (150mg – 600mg) of R-Alpha Lipoic Acid per day something to be avoided at all costs or?

  10. JP Says:

    Hi Michael,

    I’ve tried, thus far unsuccessfully, to find a genuine alpha lipoic acid to interview about potential side effects. So far, several experts have declined my request for an interview. However, I’ll keep trying to find a suitable candidate. In the meantime, here are several studies that offer a glimpse into the long and short term safety profile of this antioxidant:




    Are you taking the recommended dosage of 300 mg/day (along with the other components of the formula)? In other words, two capsules twice-daily?

    Be well!


  11. JP Says:

    Update: Alpha lipoic acid may assist with weight loss efforts …


    Obesity (Silver Spring).

    Effects of α-lipoic acid and eicosapentaenoic acid in overweight and obese women during weight loss.

    OBJECTIVE: To evaluate the potential body weight-lowering effects of dietary supplementation with eicosapentaenoic acid (EPA) and α-lipoic acid separately or combined in healthy overweight/obese women following a hypocaloric diet.

    METHODS: This is a short-term double-blind placebo-controlled study with parallel design that lasted 10 weeks. Of the randomized participants, 97 women received the allocated treatment [Control, EPA (1.3 g/d), α-lipoic acid (0.3 g/d), and EPA + α-lipoic acid (1.3 g/d + 0.3 g/d)], and 77 volunteers completed the study. All groups followed an energy-restricted diet of 30% less than total energy expenditure. Body weight, anthropometric measurements, body composition, resting energy expenditure, blood pressure, serum glucose, and insulin and lipid profile, as well as leptin and ghrelin levels, were assessed at baseline and after nutritional intervention.

    RESULTS: Body weight loss was significantly higher (P < 0.05) in those groups supplemented with α-lipoic acid. EPA supplementation significantly attenuated (P < 0.001) the decrease in leptin levels that occurs during weight loss. Body weight loss improved lipid and glucose metabolism parameters but without significant differences between groups. CONCLUSIONS: The intervention suggests that α-lipoic acid supplementation alone or in combination with EPA may help to promote body weight loss in healthy overweight/obese women following energy-restricted diets. Be well! JP

  12. JP Says:

    Update 05/26/15:


    J Alzheimers Dis. 2014;38(1):111-20.

    A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer’s disease.

    Oxidative stress, inflammation, and increased cholesterol levels are all mechanisms that have been associated with Alzheimer’s disease (AD) pathology. Several epidemiologic studies have reported a decreased risk of AD with fish consumption. This pilot study was designed to evaluate the effects of supplementation with omega-3 fatty acids alone (ω-3) or omega-3 plus alpha lipoic acid (ω-3 + LA) compared to placebo on oxidative stress biomarkers in AD. The primary outcome measure was peripheral F2-isoprostane levels (oxidative stress measure). Secondary outcome measures included performance on: Mini-Mental State Examination (MMSE), Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL), and Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). Thirty-nine AD subjects were randomized to one of three groups: 1) placebo, 2) ω-3, or 3) ω-3 + LA for a treatment duration of 12 months. Eighty seven percent (34/39) of the subjects completed the 12-month intervention. There was no difference between groups at 12 months in peripheral F2-isoprostane levels (p = 0.83). The ω-3 + LA and ω-3 were not significantly different than the placebo group in ADAS-cog (p = 0.98, p = 0.86) and in ADL (p = 0.15, p = 0.82). Compared to placebo, the ω-3 + LA showed less decline in MMSE (p < 0.01) and IADL (p = 0.01) and the ω-3 group showed less decline in IADL (p < 0.01). The combination of ω-3 + LA slowed cognitive and functional decline in AD over 12 months. Because the results were generated from a small sample size, further evaluation of the combination of omega-3 fatty acids plus alpha-lipoic acid as a potential treatment in AD is warranted. Be well! JP

  13. JP Says:

    Update 05/26/15:


    Folia Med (Plovdiv). 2013 Jan-Mar;55(1):55-63.

    Effect of transdermal testosterone or alpha-lipoic acid on erectile dysfunction and quality of life in patients with type 2 diabetes mellitus.

    Erectile dysfunction (ED) is the inability to develop and/or maintain an erection that is sufficient for satisfactory sexual intercourse. The prevalence of erectile dysfunction in diabetic men is 28-75%, this percentage rising with patient’s age and duration of diabetes. The AIM of the present study was to investigate erectile dysfunction and quality of life in patients with type 2 diabetes mellitus (T2DM) after treating them with transdermal testosterone or with alpha-lipoic acid.

    MATERIALS AND METHODS: The effect of a 12-week treatment with transdermal testosterone or alpha-lipoic acid on the erectile function and quality of life of 45 men with ED and T2DM was studied in a randomized, prospective, open clinical, comparative study. The parameters we measured in the patients were body weight and body mass index (BMI); the albumin, lipids, HbA1C, testosterone (T), sex hormone-binding globulin (SHBG), follicle stimulating hormone (FSH), luteinizing hormone (LH) and microalbuminuria levels; the International Index of Erectile Function (IIEF) and Health related quality of life (SF-36) questionnaires were completed to evaluate ED and quality of life before and after 12 weeks of treatment with alpha-lipoic acid (600 mg, parenterally, for 7 days, followed by 600 mg received per os) or with transdermal testosterone in a dose of 50 mg daily.

    RESULTS: Testosterone treatment decreased BMI significantly (p < 0.01), increased testosterone concentrations (p < 0.01) and raised the SHBG levels (p < 0.05), improved the glycemic control and lipid profile (total cholesterol, p < 0.05; HDL cholesterol, p < 0.05; triglycerides, p < 0.05). The patients treated with alpha-lipoic acid had their BMI (p < 0.01), HbA1C (p < 0.01), total cholesterol (p < 0.01), HDL-cholesterol (p < 0.01) and triglycerides (p < 0.01) significantly reduced. The indicators for ED in both groups were also statistically significantly improved. There was improvement for all patients' self-assessment score for "physical functioning" (p = 0.001), for "role limitations due to physical health" (p < 0.001) and for "general health perception" (p = 0.021). CONCLUSIONS: Transdermal testosterone and alpha-lipoic acid have a tangible beneficial effect on erectile dysfunction and on metabolic disorders in T2DM patients and can be used to treat such patients. Be well! JP

  14. JP Says:

    Updated 07/26/15:


    Fertil Steril. 2015 Jun 11.

    A randomized, triple-blind, placebo-controlled clinical trial examining the effects of alpha-lipoic acid supplement on the spermatogram and seminal oxidative stress in infertile men.

    OBJECTIVE: To evaluate effects of supplementation with alpha-lipoic acid (ALA) on the spermatogram and seminal oxidative stress biomarkers.

    DESIGN: Randomized, triple-blind, placebo-controlled clinical trial.

    SETTING: Infertility clinic.

    PATIENT(S): Infertile men.

    INTERVENTION(S): ALA (600 mg) or placebo for 12 weeks.

    MAIN OUTCOME MEASURE(S): Semen analysis, anthropometric, dietary, and physical activity assessments, total antioxidant capacity, and malondialdehyde.

    RESULT(S): At the end of study, the total sperm count, sperm concentration, and motility in the intervention group were significantly higher than in the control group. In the ALA group, the total sperm count, sperm concentration, and motility levels were also significantly increased at the end of study compared with baseline values. However, there were no significant differences in ejaculate volume, normal morphology percentage, and live sperm between groups. ALA supplementation also resulted in a significant improvement in seminal levels of total antioxidant capacity (TAC) and malondialdehyde compared with the placebo.

    CONCLUSION(S): According to the results, medical therapy of asthenoteratospermia with ALA supplement could improve quality of semen parameters. However, further investigation is suggested in this regard.

    Be well!


  15. JP Says:

    Updated 07/26/15:


    Med Oral Patol Oral Cir Bucal. 2015 Jul 1;20(4):e435-40.

    Alpha lipoic acid efficacy in burning mouth syndrome. A controlled clinical trial.

    BACKGROUND: A double-blind placebo-controlled trial was conducted in order to evaluate the efficacy of alpha lipoic acid (ALA) and determine the statistical significance of the outcome variables. Burning mouth syndrome (BMS) is defined as an oral burning sensation in the absence of clinical signs which could justify the syndrome. Recent studies suggest the existence of neurological factors as a possible cause of the disease.

    MATERIAL AND METHODS: 60 patients with BMS, in two groups: case group with 600 mg/day and placebo as control group; with follow up of 2 months.

    RESULTS: 64% of ALA patients reported some level of improvement, with a level of maintenance of 68.75% one month after treatment. 27.6% of the placebo group also demonstrated some reduction in BMS symptoms.

    CONCLUSIONS: Long-term evolution and the intensity of symptoms are variables that reduce the probability of improvement with ALA treatment.

    Be well!


  16. JP Says:

    Updated 07/26/15:


    Gynecol Endocrinol. 2015 Apr 20:1-4.

    d-chiro-Inositol and alpha lipoic acid treatment of metabolic and menses disorders in women with PCOS.

    AIM: To evaluate the effects of the combination of d-chiro-inositol (DCI) and alpha lipoic acid on menses and metabolic disorders in women with polycystic ovary syndrome (PCOS).

    METHODS: Forty-six women (26 study group subjects and 20 controls) of reproductive age with PCOS according to Rotterdam criteria were enrolled in this prospective study. Fasting serum samples were collected from each woman. Homeostasis model of insulin resistance, insulin levels, lipid profile, frequency of menstrual cycles, number of ovarian peripheral cysts and BMI of both groups were investigated at baseline and after 180 days. Clinical and metabolic aspects of women on DCI and lipoic acid treatment underwent improvement (p < 0.5) with respect to the control group. Regarding lipid profile, no statistically difference was observed in total cholesterol and triglycerides levels in both groups at follow-up with respect the baseline values (p = NS). CONCLUSION: DCI and alpha lipoic acid treatment has been thought because it plays an essential role in mithocondrial specific pathways that generate energy from glucose and its potent effect as antioxidant. The association might have a strong impact on metabolic profile even with a short-term treatment. Further investigations are needed to evaluate other effects on reproductive physiology of women with PCOS. Be well! JP

  17. JP Says:

    Updated 09/03/15:


    Med Glas (Zenica). 2015 Aug;12(2):122-7.

    Alpha-lipoic acid reduces body weight and regulates triglycerides in obese patients with diabetes mellitus.

    Aim: To determine an influence of alpha-lipoic acid to reduction of body weight and regulation of total cholesterol concentration, triglycerides and glucose serum levels in obese patients with diabetes mellitus type 2.

    Methods: A prospective study includes two groups of obese patients with diabetes mellitus and signs of peripheral polyneuropathia: examined group (30 patients; 15 females and 15 males), and control group (30 patients; 12 females and 18 males). All were treated with metformin (850-1700 mg/day). Examined patients were additionally treated with alpha-lipoic acid 600 mg/day during 20 weeks. Body mass index and concentrations of total cholesterol, triglycerides and glucose in serum were compared before and after the treatment.

    Results: The group treated with 600 mg alpha-lipoic acid lost significantly more weight, and had lower triglyceride level than the control group. There were no significant differences in total cholesterol and glucose serum levels between the groups.

    Conclusion: Alpha-lipoic acid of 600 mg/day treatment have influenced weight and triglycerides loss in obese patients with diabetes mellitus type 2. It should be considered as an important additive therapy in obese patients with diabetes mellitus type 2.

    Be well!


  18. JP Says:

    Updated 08/24/16:


    Biofactors. 2016 Aug 10.

    Effects of dietary supplementation with EPA and/or α-lipoic acid on adipose tissue transcriptomic profile of healthy overweight/obese women following a hypocaloric diet.

    In obesity, the increment of adiposity levels disrupts the whole body homeostasis, promoting an over production of oxidants and inflammatory mediators. The current study aimed to characterize the transcriptomic changes promoted by supplementation with eicosapentaenoic acid (EPA, 1.3 g/day), α-lipoic acid (0.3 g/day), or both (EPA + α-lipoic acid, 1.3 g/day + 0.3 g/day) in subcutaneous abdominal adipose tissue from overweight/obese healthy women, who followed a hypocaloric diet (30% of total energy expenditure) during ten weeks, by using a microarray approach. At the end of the intervention, a total of 33,297 genes were analyzed using Affymetrix GeneChip arrays. EPA promoted changes in extracellular matrix remodeling gene expression, besides a rise of genes associated with either chemotaxis or wound repair. α-Lipoic acid decreased expression of genes related with cell adhesion and inflammation. Furthermore, α-lipoic acid, especially in combination with EPA, upregulated the expression of genes associated with lipid catabolism while downregulated genes involved in lipids storage. Together, all these data suggest that some of the metabolic effects of EPA and α-lipoic acid could be related to their regulatory actions on adipose tissue metabolism.

    Be well!


  19. JP Says:

    Updated 12/25/16:


    Tohoku J Exp Med. 2016;240(3):209-214.

    α-Lipoic Acid Treatment Improves Vision-Related Quality of Life in Patients with Dry Age-Related Macular Degeneration.

    Dry form of age-related macular degeneration (AMD) constitutes 90% of AMD cases, and it is characterized by the formation of drusen under the retina and the slow breakdown of the light-sensing cells in the macula, which causes a gradual loss of central vision. Since oxidative stress is involved in the pathogenesis of dry AMD, α-lipoic acid (LA) with antioxidant properties was selected, and its effect on anti-oxidative markers and visual quality in patients with dry AMD was assessed. A total of 100 dry AMD patients (60-83 years old) were randomly assigned to LA treatment group (n = 50) and placebo control group (n = 50). We measured the serum superoxide dismutase (SOD) activity, an important marker of antioxidant defense, best-corrected visual acuity (BCVA), contrast sensitivity, and Chinese-Version Low Vision Quality of Life (CLVQOL) before and after LA or placebo intervention. Pearson correlation coefficients were calculated to explore the relationship between contrast sensitivity values and CLVQOL scores. There was a statistically significant increase in serum SOD activity after LA intervention. The CLVQOL score was improved significantly after LA treatment. The contrast sensitivity measured at middle and low spatial frequency was significantly higher after LA treatment. CLVQOL scores were positively correlated with contrast sensitivity at low spatial frequency (3 cyc/degree) in LA-treated group. These results indicate that LA treatment improves vision-related quality of life in patients with dry AMD probably by increasing antioxidant activity. Thus, LA can be regarded as a promising agent for the treatment of AMD.

    Be well!


  20. JP Says:

    Updated 03/18/17:


    J Med Food. 2017 Jan;20(1):79-85.

    Effects of Alpha-Lipoic Acid Supplementation on Plasma Adiponectin Levels and Some Metabolic Risk Factors in Patients with Schizophrenia.

    Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and anti-inflammatory properties and is suggested to be a biomarker of metabolic disturbances. The aim of this study was to investigate the effects of alpha-lipoic acid (ALA) on plasma adiponectin and some metabolic risk factors in patients with schizophrenia. The plasma adipokine levels (adiponectin and leptin), routine biochemical and anthropometric parameters, markers of oxidative stress, and the serum phospholipid fatty acid profile in eighteen schizophrenic patients at baseline, in the middle, and at the end of a 3-month long supplementation period with ALA (500 mg daily) were determined. A significant increase in the plasma adiponectin concentrations, as well as a decrease in fasting glucose and aspartate aminotransferase activity (AST), was found. Baseline AST activity was independently correlated with the adiponectin concentrations. Our data show that ALA can improve plasma adiponectin levels and may play a potential role in the treatment of metabolic risk factor in patients with schizophrenia. Future randomized controlled trials are needed to confirm these preliminary investigations.

    Be well!


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