LIPOIC ACID

Alpha Lipoic Acid has featured in a variety of research publications from integrative cancer care programs. Often intravenously, with garcini cambogia and low dose naltrexone , a re-purposed drug. There are multiple case studies in late stage cancer therapy, some of which show notable improvements in outcome. These pilot sudies and their effects have not, so far, been confirmed in later stage and larger clinical trials.

In metabolic and systemic inflammatory diseases, lipoic acid has demonstated positive results in a number of biomarkers that have association with cancer progression.

 

TYPICAL ABSORPTION LEVELS

30-40%

EXAMPLES OF IMPROVED OUTCOMES

YES
ANALYSIS

PRE-DIAGNOSIS OR PREVENTION

NO

Highlighted Studies

A study investigated the combination of hydroxycitrate and alpha-lipoic acid in patients with advanced metastatic cancer who had failed standard chemotherapy. The treatment was administered as part of a compassionate care regimen, where patients received hydroxycitrate (500 mg three times daily) along with other agents. Results indicated that several patients experienced partial regression or stabilization of their disease, and researchers suggested some extension to overall survival for some...

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From August 2010 to the present (November 2017), the patient’s RCC [kidney cancer] with metastasis to the left lung has been followed closely using CT and PET/CT imaging. After only a few treatments of IV ALA and IV vitamin C, his symptoms began to improve, and the patient actually regained his original baseline weight, his energy and outlook improved, his dyspnea resolved, and even returned to work. His most recent PET/CT scan demonstrated normal glucose uptake in his left lung ..The patie...

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In summary, the current meta-analysis demonstrated the promising impact of ALA administration on decreasing inflammatory markers ….The results of current meta-analysis showed that ALA supplementation significantly decreased CRP [c-reactive protein] (SMD = − 1.52), IL-6 (SMD = − 1.96), and TNF-α levels (SMD = − 2.62;) in patients with Metabolic Syndrome and related disorders

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in the groups treated with alpha lipoic acid 800 and 1200 mg/day, we registered a reduction of FPG, TC, LDL-C, and Tg compared to baseline …The values recorded in the group treated with alpha lipoic acid 1200 mg/day were significantly lower [better] compared to the ones obtained with alpha lipoic acid 400 mg/day. Moreover, alpha lipoic acid 1200 mg/day reduced Hs-CRP levels compared to baseline and compared to 400 mg/day (p < 0.05 for both)… In the group treated with alpha lipo...

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https://ar.iiarjournals.org/content/34/2/973Human study2.5Two other patients had to be switched to conventional chemotherapy combined with metabolic treatment, one of when had a subsequent dramatic tumor response. Disease in the other patients was either stable or very slowly progressive. The patient with hormone-resistant prostate cancer had a dramatic fall in Prostate-Specific Antigen (90%), which is still decreasing. Conclusion: These very primary results suggest the lack of toxicity and the probable efficacy of metabolic treatment in chemoresistant advanced carcinoma. It is also probable that metabolic treatment enhances the efficacy of cytotoxic chemotherapy. These results are in line with published animal data. A randomized clinical trial is warranted.α-LA is a drug approved in several countries (including Austria and Germany) for the treatment of diabetic polyneuropathy. It is also sold over-the-counter as an antioxidant. The treatment protocol for diabetic polyneuropathy is 600 mg per day i.v. for two to four weeks followed by 600 mg per day of the oral form, with no indication of the duration of the maintenance treatment. Higher doses have been used in clinical trials for diabetic polyneuropathy. Mcilduff and Rutkove reviewed five randomized clinical trials up to April 2011 for this indication (23). Two studies used the i.v. route alone and one study used both i.v. and oral routes. Based on these results, 600 mg per day i.v. for three weeks appears to be safe, with no more side-effects than with placebo, while 600 mg twice per day i.v. for three weeks was responsible for more side-effects than the placebo, but all were minor and reversible.
https://journals.sagepub.com/doi/10.1177/1534735417747984Human study2.5From August 2010 to the present (November 2017), the patient’s RCC with metastasis to the left lung has been followed closely using CT and PET/CT imaging. After only a few treatments of IV ALA and IV vitamin C, his symptoms began to improve, and the patient actually regained his original baseline weight, his energy and outlook improved, his dyspnea resolved, and even returned to work. His most recent PET/CT scan demonstrated normal glucose uptake in his left lung (Figure 9). The patient had stable disease with an elimination of the signs and symptoms of stage IV RCCThe key therapeutic agents initially prescribed by BB were intravenous (IV) vitamin C 25 to 50 g every morning and IV racemic α-lipoic acid (ALA) 300 to 600 mg every afternoon after a meal (to prevent hypoglycemia). These therapies were administered at the clinic on an outpatient basis. The oral protocol included low-dose naltrexone (LDN) 4.5 mg at bedtime, the oral Triple Antioxidant Therapy protocol2,3 with (1) racemic ALA 300 mg twice daily, (2) selenomethionine 200 µg twice daily, and (3) silymarin 900 mg twice a day along with 3 professional-strength B-50 complex capsules a day. Oral hydroxycitrate (HCA) 500 mg 3 times daily
https://pmc.ncbi.nlm.nih.gov/articles/PMC5989440/Human study2.5This systematic review and meta-analysis assessed the effect of ALA supplementation on inflammatory markers in patients with MetS and related disorders. Our findings supported the beneficial impact of ALA administration on lowering inflammatory markers in patients suffering from metabolic syndrome and related disorders.The results of current meta-analysis showed that ALA supplementation significantly decreased CRP [c-reactive protein] (SMD = − 1.52), IL-6 (SMD = − 1.96), and TNF-α levels (SMD = − 2.62;) in patients with Metabolic Syndrome and related disorders
https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-018-0274-yMeta-analysis2.5In summary, the current meta-analysis demonstrated the promising impact of ALA administration on decreasing inflammatory markers such as CRP, IL-6 and TNF-α among patients with MetS and related disorders...Eighteen trials out of 912 potential citations were found to be eligible for our meta-analysis. The findings indicated that ALA supplementation significantly decreased C-reactive protein (CRP) (SMD = − 1.52), interleukin-6 (IL-6) (SMD = − 1.96), and tumor necrosis factor alpha levels (TNF-α) (SMD = − 2.62) in patients diagnosed with metabolic diseases.Our findings supported the beneficial impact of ALA administration on lowering inflammatory markers in patients suffering from metabolic syndrome and related disorders. Few studies have reported the beneficial effects of antioxidant supplementation on inflammatory cytokines. In a meta-analysis conducted by Ju et al. [38], selenium supplementation significantly decreased serum CRP levels in patients with coronary heart disease, suggesting its potential impact on reducing inflammation in chronic conditions. In addition, supplementation with vitamin E in the form of either α-tocopherol or γ-tocopherol resulted in a significant reduction in CRP concentrations [39]. Available information regarding the effects of ALA supplementation on inflammatory cytokines is inconclusive. ALA supplementation for 12 months significantly decreased serum levels of common markers of inflammation in ablated patients
https://journals.sagepub.com/doi/10.1177/1534735409352082Human study2.5The integrative therapy described in this arti- cle may have the possibility of extending the life of a patient who is customarily considered terminal. This was accom- plished with a program of an antioxidant that bears known antitumor activity (namely, ALA) and an opiate blockade agent that can stimulate an endogenous immune response. As we stated in our earlier article, we believe that bio- medical science will one day develop a cure for metastatic pancreatic cancer, perhaps via gene therapy or another bio- logical-type platform. But until such protocols come to market, moreover evolve and are realized, the ALA/N ther- apy should be considered, given its lack of toxicity at levels reported herein, its ready availability, and its effect on the 4 patients discussed in this current articleThe authors, in a previous article, described the long-term survival of a man with pancreatic cancer and metastases to the liver, treated with intravenous alpha-lipoic acid and oral low-dose naltrexone (ALA/N) without any adverse effects. He is alive and well 78 months after initial presentation. Three additional pancreatic cancer case studies are presented in this article. At the time of this writing, the first patient, GB, is alive and well 39 months after presenting with adenocarcinoma of the pancreas with metastases to the liver. The second patient, JK, who presented to the clinic with the same diagnosis was treated with the ALA/N protocol and after 5 months of therapy, PET scan demonstrated no evidence of disease. The third patient, RC, in addition to his pancreatic cancer with liver and retroperitoneal metastases, has a history of B-cell lymphoma and prostate adenocarcinoma. After 4 months of the ALA/N protocol his PET scan demonstrated no signs of cancer.
https://doi.org/10.2147/DDDT.S280802Human study2In the groups treated with alpha lipoic acid 800 and 1200 mg/day, we registered a reduction of FPG, TC, LDL-C, and Tg compared to baseline (p < 0.05 for all with alpha lipoic acid 800 mg/day, and p < 0.01 for all with alpha lipoic acid 1200 mg/day). The values recorded in the group treated with alpha lipoic acid 1200 mg/day were significantly lower compared to the ones obtained with alpha lipoic acid 400 mg/day. Moreover, alpha lipoic acid 1200 mg/day reduced Hs-CRP levels compared to baseline and compared to 400 mg/day (p < 0.05 for both).The chronic use (4 years) of a food supplement containing alpha lipoic acid is well tolerated, without significant differences between lower and higher dosages and improves glycemic status and lipid profile but only if administered at high dosage....n our study, we did not observe significant side effects during the various dosages of alpha lipoic acid and we recorded an improvement of metabolic parameters with alpha lipoic acid at the dosage of 800 and 1200 mg/day, suggesting that higher doses are needed to obtain an action on glycemic and lipid parameters
https://www.nature.com/articles/s41416-020-0729-6#Sec12Lab study1Regardless of the ERα status, LA was able to inhibit crucial signalling pathways such as PI3K/Akt/mTOR and ERK in a time- and concentration-dependent manner. It is known that these pathways are directly implicated in cancer progression and especially cancer cell proliferation.38,39 Under our experimental conditions, we demonstrated that LA inhibits these pathways by suppressing the phosphorylation of Akt and ERK. Moreover, LA reinforces the Akt inhibition by activating AMPK through its phosphorylation. Accordingly, once AMPK is activated, it phosphorylates and thereby activates the TSC complex leading to mTOR inhibitionTaken together, we herein show that LA inhibits the proliferation of various ERα+ and ERα− breast cancer cell lines in vitro and ex vivo by inhibiting the maturation of IGF-1R (Fig. 6). This inhibition is the consequence of the reduction of furin expression, which is implicated in tumour aggressiveness. Nevertheless, the mechanism underlying LA downregulation of furin expression remains unclear. Though LA could be considered as a potential agent for the treatment of cancer, possibly as a supplement to systemic anticancer treatments, further in vivo studies are needed to evaluate its efficacy in combination with conventional therapy.Screenshot from 2023-12-22 15-52-35
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542233/Lab study1These data suggests that LPA can reduce (1) cell viability/proliferation, (2) uptake of [18F]-FDG and (3) lactate production and increase apoptosis in all investigated cell lines. In contrast, DCA was almost ineffective. In the mouse xenograft model with s.c. SkBr3 cells, daily treatment with LPA retarded tumor progression. Therefore, LPA seems to be a promising compound for cancer treatment.In vivo cell proliferation, as assessed by measuring of the tumor volumes, was reduced in mice treated with LPA. Furthermore, there was also a difference in the amount of [18F]-FDG uptake as observed in PET scans. T/M ratios dropped by day 14 and were approx. twice as low compared with animals that did not receive any LPA treatment. In a report of three cases, Berkson, et al. depicted that a LPA/low dose naltrexone protocol in people with metastatic and nonmetastatic pancreatic cancer resulted in [18F]-FDG PET scans without evidence of disease approximately 4 mo after treatment.23 Therefore, LPA holds the promise to have anti-proliferative properties when applied continuouslyScreenshot from 2023-12-22 16-04-52
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291200/Lab study, Lab study- adjunct 1ALA had much stronger anti-cancer effects when it was combined with chemotherapeutic agents or RT. In colorectal cancer cells, ALA enhanced the cytotoxic effect of 5-fluorouracil [6]. Pretreatment with ALA prevented RT-induced epithelial-mesenchymal transition by inhibiting radiation-induced transforming growth factor β signaling and nuclear translocation of NF-κB in MCF-7 and MDA-MB-231 cells [8]. The evidence suggests that ALA not only is cytotoxic to cancer cells but also acts as a cancer radiation sensitizer while protecting normal tissues. However, the mechanism by which ALA sensitizes cancer cells to RT remains largely unexplored. The current study is the first report showing a new mode of action (senescence induction) of ALA beyond apoptotic cell death in RT-resistant breast cancer cells.Our colleagues have demonstrated in previous studies that ALA acts as a potential radioprotector in various normal tissues during RT [9,10]. And, in this study, ALA showed synergistic effect as a radiosensitizer through cellular senescence in radioresistant breast cancer cells. From previous studies and this study, ALA appears to have an ideal dual effect, but additional experiments using other cancer cell lines or animal models are required, and well-designed clinical trials are also needed in the future for clinical use. We carefully suggest that ALA might be a potential novel pharmaceutical agent in cancer treatment and might contribute to a novel RT protocol for human cancer cells that are resistant to irradiationScreenshot from 2023-12-22 16-01-49
https://febs.onlinelibrary.wiley.com/doi/full/10.1002/2211-5463.12820Lab study1The major finding of this study is that LA, a compound found in the human diet that has been used for treating diabetic complications in humans, limited lung cancer growth in mice. The anti-lung cancer effect of LA was mediated through the mTOR-mediated inhibition of autophagy. Our data suggest that besides the treatment for diabetic complications, LA might serve as an alternative therapeutic approach for lung cancer of humans.n summary, we provide clear evidence from both in vivo and in vitro experiments that LA suppressed lung cancer growth and lung cancer cell viability. This anti-lung cancer effect of LA was mediated by the mTOR-mediated autophagy inhibition. When taken into account that LA has been used in the treatment of human diabetic complications for many years and shown no obvious adverse effects, LA might represent a meaningful therapeutic approach for lung cancer in humans.Screenshot from 2023-12-22 16-13-14
https://link.springer.com/article/10.1007/s00228-020-02844-wMeta-analysis2Eight studies were included in systematic review and seven studies in meta-analysis. The overall effect suggested a significant decrement in serum leptin concentrations (WMD = − 3.63; 95% CI, − 5.63, − 1.64 μg/ml; I2 = 80.7%) and a significant increase in serum levels of adiponectin (WMD = 1.98 μg/ml; 95% CI, 0.92, 3.04; I2 = 95.7%). Subgroup analyses based on age showed a significant reduction in leptin levels only in younger adults, and subgroup analysis based on duration indicated in studies with a duration of more than 8 weeks adiponectin levels increased significantly and leptin levels decreased significantly.New evidence suggests that dysregulation of adipocytokines caused by excess adiposity plays an important role in the pathogenesis of various obesity comorbidities. Our aim in this meta-analysis was to determine the effect of alpha-lipoic acid (ALA) supplementation on serum levels of leptin and adiponectin.

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