Alpha-Lipoic-Acid Cancer Research Results

ALA, Alpha-Lipoic-Acid: Click to Expand ⟱
Features: antioxidant, energy production in cell mitochondria
Alpha-Lipoic-Acid: also known as lipoic acid or thioctic acid (reduced form is dihydrolipoic acid).
"Universal antioxidant" because it is both water- and fat-soluble and can neutralize free radicals.
-Treatment sometimes as ALA/N (alpha-lipoic acid/low-dose naltresone)
-Also done in IV
-Decreases ROS production, but also has pro-oxidant role.
Normal adult can take 300 milligrams twice a day with food, but they should always take a B-complex vitamin with it. Because B complex vitamins, especially thiamine, and biotin, and riboflavin, are depleted during this metabolic process.
α-Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E.
-It seems a paradox that LA functions as both antioxidant and prooxidant. LA functions the pro-oxidant only in special cancer cells, such as A549 and PC9 cells which should show high-level NRF2 expression and high glycolytic level. Through inhibiting PDK1 to further prohibit NRF2; LA functions as anticancer prooxidant.

α-lipoic acid possesses excellent silver chelating properties.

ALA → ROS ↑ (cancer cells; high dose / stressed mitochondria)
ALA → ROS ↓ (normal cells; low–moderate dose)
same pattern seen with: Vitamin C, Menadione, Quercetin, EGCG, Resveratrol
- ALA acts as pro-Oxidant only in cancer cells:#278 - Pro-Oxidant Dose margin >100uM:#304

- Bioavailability: 80-90%, but conversion to EPA/DHA is 5-10% (and takes longer time).
- AI (Adequate Intake): 1.1-1.6g/day.
- human studies have shown that ALA levels decline significantly with age
- 1g of ALA might achieve 500uM in the blood.
- ALA is poorly soluble, lecithin has been used as an amphiphilic matrix to enhance its bioavailability.
- Pilot studies or observational interventions have used flaxseed supplementation (rich in ALA) in doses providing roughly 3–4 g of ALA daily.
- Flaxseed oil is even more concentrated in ALA – typical 50–60% ALA by weight.
- single walnut may contain 300mg of ALA
- chia oil contains 55-65% ALA.
- α-LA can also be obtained from the diet through the consumption of dark green leafy vegetables and meats
- ALA is more stable in chia seeds, (2grams of ALA per tablespoon)
- ALA degrades when exposed to heat, light, and air. (prone to oxidation)

-Note half-life 1-2 hrs.
BioAv 30-40% from walnuts, 60-80% from supplements. Co-ingestion with fat improves absorption. Both fat and water soluble
Pathways:
- induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑,
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, VEGF↓, FAK↓, NF-κB↓, TGF-β↓, α-SMA↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, GLUT1↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓,
- small indication of inhibiting Cancer Stem Cells : CSC↓, CD24↓, β-catenin↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Cancer-Relevant Pathways
Rank Pathway / Axis Cancer Cells Normal Cells Label Interpretation Notes
1 Reactive oxygen species (ROS) ↑ ROS (dose- & stress-dependent) ↓ ROS Conditional Driver Biphasic redox behavior ALA/DHLA redox cycling can push already stressed cancer mitochondria past tolerance while buffering ROS in normal cells
2 Glutathione (GSH) system ↓ functional buffering ↑ GSH regeneration Secondary Redox amplification vs protection In cancer cells, GSH consumption accompanies ROS escalation; in normal cells DHLA supports GSH recycling
3 Mitochondrial function (ΔΨm) ↓ ΔΨm (stress-induced) ↔ stabilized Secondary Mitochondrial selectivity Cancer cells with unstable ETC show depolarization; normal cells tolerate or benefit metabolically
4 NF-κB signaling ↓ survival signaling ↓ inflammatory tone Secondary Redox-sensitive transcription NF-κB suppression reduces cancer cell survival programs but is anti-inflammatory in normal tissue
5 Cell proliferation ↓ proliferation ↔ spared Phenotypic Cytostatic selectivity ALA slows cancer cell cycling without universal apoptosis
6 Apoptosis ↑ apoptosis (conditional) ↓ apoptosis Phenotypic Threshold-dependent death Occurs in cancer cells when redox stress exceeds buffering capacity
7 NRF2 antioxidant response ↑ NRF2 (adaptive, often insufficient) ↑ NRF2 (protective) Adaptive Stress compensation NRF2 reflects attempted redox recovery; not a kill mechanism


Scientific Papers found: Click to Expand⟱
279- ALA,    Lipoic acid-induced oxidative stress abrogates IGF-1R maturation by inhibiting the CREB/furin axis in breast cancer cell lines
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Furin↓, IGF-1R↓, ROS↑, CREB↓, Furin↓, IGF-1R↓,
278- ALA,    The Multifaceted Role of Alpha-Lipoic Acid in Cancer Prevention, Occurrence, and Treatment
- Review, NA, NA
ROS↑, NRF2↑, Inflam↓, frataxin↑, *BioAv↓, ChemoSen↑, Hif1a↓, eff↑, FAK↓, ITGB1↓, MMP2↓, MMP9↓, EMT↓, Snail↓, Vim↓, Zeb1↓, P53↑, MGMT↓, Mcl-1↓, Bcl-xL↓, Bcl-2↓, survivin↓, Casp3↑, Casp9↑, BAX↑, p‑Akt↓, GSK‐3β↓, *antiOx↑, *ROS↓, selectivity↑, angioG↓, MMPs↓, NF-kB↓, ITGB3↓, NADPH↓,
277- ALA,    α-lipoic acid modulates prostate cancer cell growth and bone cell differentiation
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, C4-2B
ROS↑, Hif1a↑, JNK↑, Casp3↑, P21↑, BAX↑, Bcl-xL↓, cFos↓,
276- ALA,    Alpha lipoic acid diminishes migration and invasion in hepatocellular carcinoma cells through an AMPK-p53 axis
- in-vitro, HCC, HepG2 - in-vitro, HCC, Hep3B
P53↑, EMT↓, AMPK↑, cycD1/CCND1↓, TumCMig↓,
274- ALA,  LDN,    Revisiting the ALA/N (alpha-lipoic acid/low-dose naltrexone) protocol for people with metastatic and nonmetastatic pancreatic cancer: a report of 3 new cases
- Human, PC, NA
OS↑,
285- ALA,  HCA,    Tolerance of oral lipoid acid and hydroxycitrate combination in cancer patients: first approach of the cancer metabolism research group
- Human, Var, NA
PI3K↝, AMPK↝, TumCG↓, *toxicity↓, Weight∅,
271- ALA,  VitC,  LDN,    The Long-Term Survival of a Patient With Stage IV Renal Cell Carcinoma Following an Integrative Treatment Approach Including the Intravenous α-Lipoic Acid/Low-Dose Naltrexone Protocol
OS↑, Weight↑, TumVol↓,
267- ALA,    α-Lipoic Acid Targeting PDK1/NRF2 Axis Contributes to the Apoptosis Effect of Lung Cancer Cells
- vitro+vivo, Lung, A549 - vitro+vivo, Lung, PC9
Apoptosis↑, ROS↑, PDK1↓, NRF2↓, PDK1↓, Bcl-2↓, Casp9↑, Dose∅,
266- ALA,    Lipoic acid decreases Mcl-1, Bcl-xL and up regulates Bim on ovarian carcinoma cells leading to cell death
- in-vitro, Ovarian, IGROV1
Mcl-1↓, Bcl-xL↓, BIM↑, ROS↑,
265- ALA,    Alpha-Lipoic Acid Reduces Cell Growth, Inhibits Autophagy, and Counteracts Prostate Cancer Cell Migration and Invasion: Evidence from In Vitro Studies
- in-vitro, Pca, LNCaP - in-vitro, Pca, DU145
ROS↓, SOD↓, GSTP1/GSTπ↓, NRF2↓, p62↓, p62↑, SOD↑, p‑mTOR↑, Beclin-1↓, ROS↑, SOD1↑,
264- ALA,    α-Lipoic acid induces Endoplasmic Reticulum stress-mediated apoptosis in hepatoma cells
- in-vitro, HCC, FaO
ROS↑, P53↑, ER Stress↑, UPR↑, CHOP↑, PDI↑, GRP78/BiP↑, GRP58↓,
263- ALA,    Alpha-lipoic acid induces p27Kip-dependent cell cycle arrest in non-transformed cell lines and apoptosis in tumor cell lines
- in-vitro, SCC, Jurkat - in-vitro, SCC, FaDu
p27↑,
262- ALA,    Lipoic acid decreases breast cancer cell proliferation by inhibiting IGF-1R via furin downregulation
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
TumCP↓, Akt↓, ERK↓, IGF-1R↓, Furin↓, Ki-67↓, AMPK↑, mTOR↓,
261- ALA,    The natural antioxidant alpha-lipoic acid induces p27(Kip1)-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells
- in-vitro, BC, MCF-7
ROS↓, Akt↓, p27↑, Bax:Bcl2↑,
260- ALA,    The effects of alpha-lipoic acid on breast of female albino rats exposed to malathion: Histopathological and immunohistochemical study
- in-vivo, BC, NA
PCNA↓, P53↓, Apoptosis↑, BAX↑,
258- ALA,    Effects of α-lipoic acid on cell proliferation and apoptosis in MDA-MB-231 human breast cells
- in-vitro, BC, MDA-MB-231
TumCG↓, p‑Akt↓, Akt↓, HER2/EBBR2↓, Bcl-2↓, BAX↑, Casp3↑,
296- ALA,    Lipoic acid inhibits cell proliferation of tumor cells in vitro and in vivo
- vitro+vivo, neuroblastoma, SK-N-SH - vitro+vivo, BC, SkBr3
TumCG↓, Casp3↑,
304- ALA,    alpha-Lipoic acid induces apoptosis in human colon cancer cells by increasing mitochondrial respiration with a concomitant O2-*-generation
- in-vitro, Colon, HT-29
mt-ROS↑, Apoptosis↑, Casp3↑, DNAdam↑, Bcl-xL↓, Dose↝,
303- ALA,  LDN,    The long-term survival of a patient with pancreatic cancer with metastases to the liver after treatment with the intravenous alpha-lipoic acid/low-dose naltrexone protocol

302- ALA,    The Antioxidant Alpha-Lipoic Acid Inhibits Proliferation and Invasion of Human Gastric Cancer Cells via Suppression of STAT3-Mediated MUC4 Gene Expression
- in-vitro, GC, AGS - in-vitro, GC, BGC-823 - in-vitro, GC, MKN-28
MUC4↓, STAT3↓,
301- ALA,  PacT,  doxoR,    Role of alpha-lipoic acid in counteracting paclitaxel- and doxorubicin-induced toxicities: a randomized controlled trial in breast cancer patients
- Human, BC, NA
BNP↓, TNF-α↓, MDA↓, NeuroT↓,
1124- ALA,    Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells
- in-vitro, Thyroid, BCPAP - in-vitro, Thyroid, HTH-83 - in-vitro, Thyroid, CAL-62 - in-vitro, Thyroid, FTC-133 - in-vivo, NA, NA
TumCP↓, AMPK↑, mTOR↓, TumCMig↓, TumCI↓, EMT↓, E-cadherin↑, β-catenin/ZEB1↓, Vim↓, Snail↓, Twist↓, TGF-β↓, p‑SMAD2↓, TumCG↓,
299- ALA,  Cisplatin,  PacT,    Anti-cancer effects of alpha lipoic acid, cisplatin and paclitaxel combination in the OVCAR-3 ovarian adenocarcinoma cell line
- in-vitro, Ovarian, OVCAR-3
MMP9↓, MMP11↓, MAPK↓,
298- ALA,  Rad,    Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1
- in-vitro, BC, MDA-MB-231
Apoptosis↑, P53↑, p38↑, NF-kB↑, TumCCA↑,
297- ALA,    Insights on the Use of α-Lipoic Acid for Therapeutic Purposes
- Review, BC, SkBr3 - Review, neuroblastoma, SK-N-SH - Review, AD, NA
PDH↑, TumCG↓, ROS↑, AMPK↑, EGR4↓, Half-Life↓, BioAv↝, *GSH↑, *IronCh↑, *ROS↓, *antiOx↑, *neuroP↑, *Ach↑, *lipid-P↓, *IL1β↓, *IL6↓, TumCP↓, FDG↓, Apoptosis↑, AMPK↑, mTOR↓, EGFR↓, TumCI↓, TumCMig↓, *memory↑, *BioAv↑, *BioAv↝, *other↓, *other↝, *Half-Life↓, *BioAv↑, *ChAT↑, *GlucoseCon↑,
295- ALA,    α-Lipoic acid suppresses migration and invasion via downregulation of cell surface β1-integrin expression in bladder cancer cells
- in-vitro, Bladder, T24/HTB-9
ITGB1↓, TumCMig↓, ERK↓, Akt↓,
291- ALA,  HCA,  MET,  Dicl,    Metabolic therapies inhibit tumor growth in vivo and in silico
- in-vivo, Melanoma, B16-F10 - in-vivo, Lung, LL/2 (LLC1) - in-vivo, Bladder, MBT-2
TumCG↓,
290- ALA,  HCA,    A combination of alpha lipoic acid and calcium hydroxycitrate is efficient against mouse cancer models: preliminary results
- vitro+vivo, Melanoma, B16-F10
TumCG↓, OS↑,
289- ALA,  HCA,  EA,    Cancer Metabolism: Fasting Reset, the Keto-Paradox and Drugs for Undoing
- Analysis, NA, NA
ACLY↓,
288- ALA,  HCA,  CAP,  Octr,    Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin
TumCG↓,
287- ALA,  HCA,  Lyco,    Metabolic treatment of cancer: intermediate results of a prospective case series
PSA↓, OS↑,
1235- ALA,  Cisplatin,    α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway
- in-vitro, Nor, HEI-OC1 - ex-vivo, NA, NA
ROS↑, HO-1↓, *toxicity↓, chemoP↑, *ROS↓, *HO-1↑, *SOD1↑, *NRF2↑,
286- HCA,  ALA,    Adding a combination of hydroxycitrate and lipoic acid (METABLOC™) to chemotherapy improves effectiveness against tumor development: experimental results and case report
OS↑,
1628- HCA,  ALA,    Addition of Hydroxy Citrate improves effect of ALA
- Review, Var, NA
ACLY↓, other↓, ROS↑, eff↑, PDKs↓,
1255- PI,  ALA,    Antileukemic effects of piperlongumine and alpha lipoic acid combination on Jurkat, MEC1 and NB4 cells in vitro
- in-vitro, CLL, NA
COX2↓, Casp3↑,
609- VitC,  ALA,  VitK3,  Se,    Vitamin C and Cancer: Is There A Use For Oral Vitamin C?
OS↑,
300- VitC,  ALA,    Combination of High-Dose Parenteral Ascorbate (Vitamin C) and Alpha-Lipoic Acid Failed to Enhance Tumor-Inhibitory Effect But Increased Toxicity in Preclinical Cancer Models
- in-vitro, BC, MDA-MB-231 - in-vitro, Colon, HCT116 - in-vitro, Ovarian, PANC1 - in-vitro, Pca, PC3
TumCG∅,

Showing Research Papers: 51 to 87 of 87
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 87

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

frataxin↑, 1,   GSTP1/GSTπ↓, 1,   HO-1↓, 1,   MDA↓, 1,   NRF2↓, 2,   NRF2↑, 1,   ROS↓, 2,   ROS↑, 10,   mt-ROS↑, 1,   SOD↓, 1,   SOD↑, 1,   SOD1↑, 1,  

Core Metabolism/Glycolysis ⓘ

ACLY↓, 2,   AMPK↑, 5,   AMPK↝, 1,   CREB↓, 1,   FDG↓, 1,   NADPH↓, 1,   PDH↑, 1,   PDK1↓, 2,   PDKs↓, 1,  

Cell Death ⓘ

Akt↓, 4,   p‑Akt↓, 2,   Apoptosis↑, 5,   BAX↑, 4,   Bax:Bcl2↑, 1,   Bcl-2↓, 3,   Bcl-xL↓, 4,   BIM↑, 1,   Casp3↑, 6,   Casp9↑, 2,   GRP58↓, 1,   JNK↑, 1,   MAPK↓, 1,   Mcl-1↓, 2,   p27↑, 2,   p38↑, 1,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   p62↓, 1,   p62↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   MGMT↓, 1,   P53↓, 1,   P53↑, 4,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   P21↑, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 1,   EMT↓, 3,   ERK↓, 2,   GSK‐3β↓, 1,   IGF-1R↓, 3,   mTOR↓, 3,   p‑mTOR↑, 1,   PI3K↝, 1,   STAT3↓, 1,   TumCG↓, 8,   TumCG∅, 1,  

Migration ⓘ

E-cadherin↑, 1,   FAK↓, 1,   Furin↓, 3,   ITGB1↓, 2,   ITGB3↓, 1,   Ki-67↓, 1,   MMP11↓, 1,   MMP2↓, 1,   MMP9↓, 2,   MMPs↓, 1,   MUC4↓, 1,   NeuroT↓, 1,   p‑SMAD2↓, 1,   Snail↓, 2,   TGF-β↓, 1,   TumCI↓, 2,   TumCMig↓, 4,   TumCP↓, 3,   Twist↓, 1,   Vim↓, 2,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 1,   EGR4↓, 1,   Hif1a↓, 1,   Hif1a↑, 1,   PDI↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   Inflam↓, 1,   NF-kB↓, 1,   NF-kB↑, 1,   PSA↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

BNP↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   ChemoSen↑, 1,   Dose↝, 1,   Dose∅, 1,   eff↑, 2,   Half-Life↓, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   HER2/EBBR2↓, 1,   Ki-67↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,   OS↑, 6,   TumVol↓, 1,   Weight↑, 1,   Weight∅, 1,  
Total Targets: 117

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   GSH↑, 1,   HO-1↑, 1,   lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 3,   SOD1↑, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Core Metabolism/Glycolysis ⓘ

GlucoseCon↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 1,   other↓, 1,   other↝, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   IL6↓, 1,  

Synaptic & Neurotransmission ⓘ

ChAT↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   BioAv↝, 1,   Half-Life↓, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

memory↑, 1,   neuroP↑, 1,   toxicity↓, 2,  
Total Targets: 23

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:29  Target#:%  State#:%  Dir#:%
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