Alpha-Lipoic-Acid / BioAv 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


BioAv, bioavailability: Click to Expand ⟱
Source:
Type: measurement
Bioavailability (usually in %) absorbed by the body.
Scientific Papers found: Click to Expand⟱
3443- ALA,    Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention
- Review, Var, NA - Review, AD, NA
*antiOx↑, *ROS↓, *IronCh↑, *cognitive↑, *cardioP↓, AntiCan↑, *neuroP↑, *Inflam↓, *BioAv↓, *AntiAge↑, *Half-Life↓, *BioAv↝, other↝, EGFR↓, Akt↓, ROS↓, TumCCA↑, p27↑, PDH↑, Glycolysis↓, ROS↑, *eff↑, *memory↑, *motorD↑, *GutMicro↑,
3551- ALA,    Alpha lipoic acid treatment in late middle age improves cognitive function: Proteomic analysis of the protective mechanisms in the hippocampus
- in-vivo, AD, NA
*cognitive↑, *Apoptosis↓, *Inflam↓, *antiOx↑, *BioAv↝, *neuroP↑,
3549- ALA,    Important roles of linoleic acid and α-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia
- Review, AD, NA
*Inflam↓, *other↝, *other↝, *neuroP↑, *BioAv↝, *adiP↑, *BBB↑, *Casp6↓, *Casp9↓, *TNF-α↓, *IL6↓, *IL1β↓, *ROS↓, *NO↓, *iNOS↓, *COX2↓, *JNK↓, *p‑NF-kB↓, *Aβ↓, *BP↓, *memory↑, *cAMP↑, *ERK↑, *Akt↑, cognitive?,
3545- ALA,    Potential therapeutic effects of alpha lipoic acid in memory disorders
- Review, AD, NA
*neuroP↑, *Inflam↓, *VCAM-1↓, *5HT↑, *memory↑, *BioAv↝, *Half-Life↓, *NF-kB↓, *antiOx↑, *IronCh↑, *ROS↓, *ATP↑, *ChAT↑, *Ach↑, *cognitive↑, *lipid-P↓, *VitC↑, *VitE↑, *GSH↑, *SOD↑, *Catalase↑, *GPx↑, *Aβ↓,
3539- ALA,    Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
- Review, AD, NA
*ROS↓, *IronCh↑, *GSH↑, *antiOx↑, *NRF2↑, *MMP9↓, *VCAM-1↓, *NF-kB↓, *cognitive↑, *Inflam↓, *BioAv↝, *BioAv↝, *BBB↑, *H2O2∅, *neuroP↑, *PKCδ↑, *ERK↑, *MAPK↑, *PI3K↑, *Akt↑, *PTEN↓, *AMPK↑, *GLUT4↑, *GlucoseCon↑, *BP↝, *eff↑, *ICAM-1↓, *VCAM-1↓, *Dose↝,
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↑,

Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,   ROS↑, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 2,   FDG↓, 1,   Glycolysis↓, 1,   PDH↑, 2,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 1,   p27↑, 1,  

Transcription & Epigenetics ⓘ

other↝, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↓, 1,   TumCG↓, 1,  

Migration ⓘ

TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 2,   EGR4↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   Half-Life↓, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 2,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cognitive?, 1,  
Total Targets: 23

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 5,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 3,   H2O2∅, 1,   lipid-P↓, 2,   NRF2↑, 1,   ROS↓, 5,   SOD↑, 1,   VitC↑, 1,   VitE↑, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 4,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,  

Core Metabolism/Glycolysis ⓘ

adiP↑, 1,   AMPK↑, 1,   cAMP↑, 1,   GlucoseCon↑, 2,  

Cell Death ⓘ

Akt↑, 2,   Apoptosis↓, 1,   Casp6↓, 1,   Casp9↓, 1,   iNOS↓, 1,   JNK↓, 1,   MAPK↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 2,   other↓, 1,   other↝, 3,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 2,   PI3K↑, 1,   PTEN↓, 1,  

Migration ⓘ

MMP9↓, 1,   PKCδ↑, 1,   VCAM-1↓, 3,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Barriers & Transport ⓘ

BBB↑, 2,   GLUT4↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   ICAM-1↓, 1,   IL1β↓, 2,   IL6↓, 2,   Inflam↓, 5,   NF-kB↓, 2,   p‑NF-kB↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

5HT↑, 1,   ChAT↑, 2,  

Protein Aggregation ⓘ

Aβ↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   BioAv↝, 7,   Dose↝, 1,   eff↑, 2,   Half-Life↓, 3,  

Clinical Biomarkers ⓘ

BP↓, 1,   BP↝, 1,   GutMicro↑, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

AntiAge↑, 1,   cardioP↓, 1,   cognitive↑, 4,   memory↑, 4,   motorD↑, 1,   neuroP↑, 6,  
Total Targets: 63

Scientific Paper Hit Count for: BioAv, bioavailability
6 Alpha-Lipoic-Acid
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#:792  State#:%  Dir#:4
  wNotes=0  sortOrder:rid,rpid

 

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