Alpha-Lipoic-Acid / BBB 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


BBB, Blood-Brain Barrier Permeability: Click to Expand ⟱
Source:
Type:
Blood-Brain Barrier(BBB) is a term often used regarding if a product has the ability to cross the BBB.
Scientific Papers found: Click to Expand⟱
3444- ALA,    Alpha-Lipoic Acid Nootropic Review: Benefits, Use, Dosage & Side Effects
- Review, NA, NA
*BBB↑, *cognitive↑, *neuroP↑, *antiOx↑,
3284- ALA,    Alpha-Lipoic Acid Mediates Clearance of Iron Accumulation by Regulating Iron Metabolism in a Parkinson's Disease Model Induced by 6-OHDA
- vitro+vivo, Park, NA
*antiOx↑, *IronCh↑, *neuroP↑, *ROS↓, *Iron↓, *BBB↑, *motorD↑, *GSH↑,
3272- ALA,    Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
- Review, AD, NA
*antiOx↑, *glucose↑, *eNOS↑, *NRF2↑, *MMP9↓, *VCAM-1↓, *NF-kB↓, *cardioP↑, *cognitive↑, *eff↓, *BBB↑, *IronCh↑, *GSH↑, *PKCδ↑, *ERK↑, *p38↑, *MAPK↑, *PI3K↑, *Akt↑, *PTEN↓, *AMPK↑, *GLUT4↑, *GLUT1↑, *Inflam↓,
3271- ALA,    Decrypting the potential role of α-lipoic acid in Alzheimer's disease
- Review, AD, NA
*antiOx↑, *memory↑, *neuroP↑, *Inflam↓, *IronCh↑, *NRF2↑, *BBB↑, *GlucoseCon↑, *Ach↑, *ROS↓, *p‑tau↓, *Aβ↓, *cognitive↑, *Hif1a↑, *Ca+2↓, *GLUT3↑, *GLUT4↑, *HO-1↑, *VEGF↑, *PDKs↓, *PDH↑, *VCAM-1↓, *GSH↑, *NRF2↑, *hepatoP↑, *ChAT↑,
3269- ALA,    Sulfur-containing therapeutics in the treatment of Alzheimer’s disease
- NA, AD, NA
*AChE↓, *GlucoseCon↑, *ACC↑, *GSH↑, *Aβ↓, *Catalase↑, *GSR↑, *GSTs↑, *NADPH↑, *NQO1↑, *iNOS↓, *NF-kB↓, *lipid-P↓, *BBB↑, *memory↑, *cognitive↑, *antiOx↑, *Inflam↓,
3550- ALA,    Mitochondrial Dysfunction and Alpha-Lipoic Acid: Beneficial or Harmful in Alzheimer's Disease?
- Review, AD, NA
*antiOx↑, *Inflam↓, *PGE2↓, *COX2↓, *iNOS↓, *TNF-α↓, *IL1β↓, *IL6↓, *BioAv↓, *Ach↑, *ROS↓, *cognitive↑, *neuroP↑, *BBB↑, *Half-Life↓, *BioAv↑, *Casp3↓, *Casp9↓, *ChAT↑, *cognitive↑, *eff↑, *cAMP↑, *IL2↓, *INF-γ↓, *TNF-α↓, *SIRT1↑, *SOD↑, *GPx↑, *MDA↓, *NRF2↑,
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?,
3548- ALA,    How Alpha Linolenic Acid May Sustain Blood–Brain Barrier Integrity and Boost Brain Resilience against Alzheimer’s Disease
- Review, AD, NA
*BBB↑, *other↑, *other↑, *DHA↑, *neuroP↑, *ROS↓, *other?,
3546- ALA,    Cognitive and Mood Effect of Alpha-Lipoic Acid Supplementation in a Nonclinical Elder Sample: An Open-Label Pilot Study
- Study, AD, NA
*antiOx↑, *ROS↓, *cognitive∅, *lipid-P↓, *memory↑, *ChAT↑, *Acetyl-CoA↑, *Aβ↓, *BioAv↑, *BBB↑, *toxicity∅,
3544- ALA,    Alpha lipoic acid for dementia
- Review, AD, NA
*antiOx↑, *BBB↑, *VitC↑, *VitE↑, *GSH↑, *IronCh↑, *neuroP↑, *NO↓, *cognitive↑, *AntiAge↑, *memory↑, *ROS↓,
3542- ALA,    Chelation: Harnessing and Enhancing Heavy Metal Detoxification—A Review
- Review, Var, NA
*antiOx↑, *VitE↑, *VitC↑, *GSH↑, *IronCh↑, *BioAv↑, *BBB↑,
3541- ALA,    Insights on alpha lipoic and dihydrolipoic acids as promising scavengers of oxidative stress and possible chelators in mercury toxicology
- Review, Var, NA
*antiOx↑, *IronCh↑, *GSH↑, *BBB↑, Apoptosis↑, MMP↓, ROS↑, lipid-P↑, PARP1↑, Casp3↑, Casp9↑, *NRF2↑, *GSH↑, *ROS↓, RenoP↑, ChemoSen↑, *BG↓,
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↝,

Showing Research Papers: 1 to 13 of 13

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 13

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

lipid-P↑, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   Casp3↑, 1,   Casp9↑, 1,  

DNA Damage & Repair ⓘ

PARP1↑, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,  

Functional Outcomes ⓘ

cognitive?, 1,   RenoP↑, 1,  
Total Targets: 10

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 11,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 9,   GSR↑, 1,   GSTs↑, 1,   H2O2∅, 1,   HO-1↑, 1,   Iron↓, 1,   lipid-P↓, 2,   MDA↓, 1,   NQO1↑, 1,   NRF2↑, 6,   ROS↓, 9,   SOD↑, 1,   VitC↑, 2,   VitE↑, 2,  

Metal & Cofactor Biology ⓘ

IronCh↑, 7,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 1,   Acetyl-CoA↑, 1,   adiP↑, 1,   AMPK↑, 2,   cAMP↑, 2,   DHA↑, 1,   glucose↑, 1,   GlucoseCon↑, 3,   NADPH↑, 1,   PDH↑, 1,   PDKs↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↑, 3,   Casp3↓, 1,   Casp6↓, 1,   Casp9↓, 2,   iNOS↓, 3,   JNK↓, 1,   MAPK↑, 2,   p38↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 2,   other?, 1,   other↑, 2,   other↝, 2,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 3,   PI3K↑, 2,   PTEN↓, 2,  

Migration ⓘ

Ca+2↓, 1,   MMP9↓, 2,   PKCδ↑, 2,   VCAM-1↓, 4,  

Angiogenesis & Vasculature ⓘ

eNOS↑, 1,   Hif1a↑, 1,   NO↓, 2,   VEGF↑, 1,  

Barriers & Transport ⓘ

BBB↑, 13,   GLUT1↑, 1,   GLUT3↑, 1,   GLUT4↑, 3,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   ICAM-1↓, 1,   IL1β↓, 2,   IL2↓, 1,   IL6↓, 2,   INF-γ↓, 1,   Inflam↓, 6,   NF-kB↓, 3,   p‑NF-kB↓, 1,   PGE2↓, 1,   TNF-α↓, 3,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   ChAT↑, 3,   p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 4,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

BG↓, 1,   BP↓, 1,   BP↝, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

AntiAge↑, 1,   cardioP↑, 1,   cognitive↑, 8,   cognitive∅, 1,   hepatoP↑, 1,   memory↑, 5,   motorD↑, 1,   neuroP↑, 8,   toxicity∅, 1,  
Total Targets: 92

Scientific Paper Hit Count for: BBB, Blood-Brain Barrier Permeability
13 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#:1123  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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