HCA, HydroxyCitric Acid: Click to Expand ⟱
Features:
HCA is a naturally occurring compound primarily known for its potential effects on appetite and lipid metabolism via inhibition of ATP citrate lyase.
Derivative of citric acid that is found in a variety of tropical plants including Garcinia cambogia and Hibiscus sabdariffa

• Hydroxy-Citric Acid (HCA) is a compound extracted from Garcinia cambogia, primarily recognized for its potential effects on lipid metabolism and appetite suppression.
• It has been proposed to inhibit the enzyme ATP citrate lyase, which is involved in converting citrate into acetyl-CoA—a key step in fatty acid synthesis.
• By modulating lipid synthesis pathways, HCA has been studied in the context of obesity and metabolic disorders, with some exploratory research considering its implications in cancer metabolism.

• Inhibition of ATP Citrate Lyase (ACLY)******
ACLY converts citrate into acetyl-CoA, a building block for fatty acid and cholesterol synthesis. Many cancer cells upregulate lipid synthesis to support membrane production and energy storage; hence, inhibiting ACLY presents a potential strategy to disrupt cancer cell metabolism.

• Impact on Lipogenesis
Reduced acetyl-CoA production can impair de novo lipogenesis, potentially limiting the proliferation of rapidly dividing cells that have high lipid demands.

• Interactions with Other Metabolic Pathways (modulation of citrate levels may affect the TCA cycle)

-Dosages used in weight loss studies typically ranging from 500 mg to 1500 mg per day
Human cyclists: 3.1 mL/kg body wt of an HCA solution (19 g/L) --> 248mg
"Studies have shown that humans can safely ingest 13.5 g of hydroxycitrate per day with plasma levels of 82 mg/L (0.39 mM) achieved"
Typically, HCA used in dietary weight loss supplement is bound to calcium, which results in a poorly soluble (<50%) and less bioavailable form. Conversely, the structural characteristics of a novel Ca2+/K+ bound (-)-HCA salt (HCA-SX or Super CitriMax) make it completely water soluble as well as bioavailable.

-HydroxyCitrate (HCA) typically used in a dose of about 1.5g/day or more for cancer (inhibition of the Melavonate Pathway?)
Scientific Papers found: Click to Expand⟱
287- ALA,  HCA,  Lyco,    Metabolic treatment of cancer: intermediate results of a prospective case series
PSA↓, one patient
OS↑,

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↓, delays tumor growth in mice

289- ALA,  HCA,  EA,    Cancer Metabolism: Fasting Reset, the Keto-Paradox and Drugs for Undoing
- Analysis, NA, NA
ACLY↓,

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↑,

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↓,

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↓, No hepatic toxicity found, no weight loss, no hypoglycemia
Weight∅,

1414- HCA,    Bioefficacy of a novel calcium-potassium salt of (-)-hydroxycitric acid
- Human, Nor, NA
*BioAv↑, Typically, HCA used in dietary weight loss supplement is bound to calcium, which results in a poorly soluble (<50%) and less bioavailable form. Conversely, the structural characteristics of a novel Ca2+/K+ bound (-)-HCA salt (HCA-SX or Super CitriMax

1637- HCA,  OLST,    Orlistat and Hydroxycitrate Ameliorate Colon Cancer in Rats: The Impact of Inflammatory Mediators
- in-vivo, Colon, NA
TumVol↓, Administration of orlistat and HCA improved the measured markers of a colon tumor
OS↑, orlistat and hydroxycitrate (135 mg/kg/day) decreased ACF incidence and mortality rate in the groups treated with DMH and/or HFD.
*IL6↓, orlistat and hydroxycitrate show decreased IL-6
*NF-kB↓, co-treatment of orlistat and hydroxycitrate record a significant reduction in the NF-kB
*eff↑, protective effects of orlistat and hydroxycitrate (HCA) against dimethylhydrazine (DMH) and high-fat diet (HFD)-i
*Casp3↓, rats supplemented with orlistat and hydroxycitrate show a decrease in the caspase-3 tissue content
*TNF-α↓, orlistat and hydroxycitrate administration to the treated rats substantially reduced the colonic TNF-α tissue
*Catalase↑, orlistat and hydroxycitrate show an increase in the colonic CAT content
*NO↓, orlistat and hydroxycitrate show a significant reduction in the colonic NO content
*ROS↓, orlistat and hydroxycitrate can potentially ameliorate the pathological lesions in the colon and reducing oxidative stress, inflammation, and apoptosis which are considered critical mechanisms for preventing colon cancer
*Inflam↓,
*Apoptosis↓,

1635- HCA,    Hydroxycitric acid prevents hyperoxaluric-induced nephrolithiasis and oxidative stress via activation of the Nrf2/Keap1 signaling pathway
- vitro+vivo, Nor, NA
*other↓, HCA administration significantly reduced crystal deposition and kidney injury induced by glyoxylate
*ROS↓, alleviated oxidative stress via upregulating the antioxidant enzyme activities of superoxide dismutase (SOD) and catalase (CAT) and reducing the malondialdehyde (MDA) content
*SOD↑,
*Catalase↑,
*MDA↓,
*NRF2↑, via activating Nrf2/Keap1

1634- HCA,    Hydroxycitrate: a potential new therapy for calcium urolithiasis
- Human, Nor, NA
*other↑, hydroxycitrate was shown to dissolve calcium oxalate crystals in supersaturated solution in vitro.
*eff↑, require appropriate research studies before hydroxycitrate can be recommended as a therapy for kidney stones.

1633- HCA,    Hydroxycitric Acid Alleviated Lung Ischemia-Reperfusion Injury by Inhibiting Oxidative Stress and Ferroptosis through the Hif-1α Pathway
- in-vivo, NA, NA - in-vitro, Nor, HUVECs
*other↓, HCA effectively attenuated lung injury, inflammation, and edema induced by ischemia reperfusion
*Inflam↓,
*MDA↓, HCA treatment significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels
*ROS↓,
*Iron↓, while decreasing iron content and increasing superoxide dismutase (SOD)
*SOD↓,
*Hif1a↓, HCA administration significantly inhibited Hif-1α and HO-1 upregulation both in vivo and in vitro.
*HO-1↓,

1631- HCA,    An overview of the safety and efficacy of a novel, natural(-)-hydroxycitric acid extract (HCA-SX) for weight management
- Review, Obesity, NA
*ACLY↓, HCA is a competitive inhibitor of ATP citrate lyase
*toxicity∅, No remarkable toxicity results were detected, demonstrating the safety of HCA-SX.
*Dose∅, 4666.7 mg HCA-SX (providing 2,800 mg HCA) in three equally divided doses 30-60 min before meals,

1630- HCA,    Chemistry and biochemistry of (-)-hydroxycitric acid from Garcinia
- Review, NA, NA
ACLY↓, HCA was shown to be a potent inhibitor of ATP citrate lyase
FASN↓, Extensive animal studies indicated that (-)-HCA suppresses the fatty acid synthesis, lipogenesis, food intake, and induced weight loss.
lipoGen↓,
Weight↓,

1629- HCA,  Tam,    Hydroxycitric acid reverses tamoxifen resistance through inhibition of ATP citrate lyase
- in-vitro, BC, MCF-7
ACLY↓, Hydroxycitric acid (HCA) is a powerful competitive inhibitor of the enzyme ACLY
eff↓, co-treatment synergistically diminished LCC2 and MCF7 cell viability
tumCV↓,
eff↑, co-treatment decreases the expression level of ACLY in LCC2 by 74 %, while in MCF7 by only 59 %
Casp3↑,
BAX↑,
Bcl-2↓,

1628- HCA,  ALA,    Addition of Hydroxy Citrate improves effect of ALA
- Review, Var, NA
ACLY↓, Hydroxycitrate is a known inhibitor of ATP citrate lyase ( also called ATP-citric synthase
other↓, Lipoic Acid Increases PDC (pyruvate dehydrogenase complex)
ROS↑, oxidative onslaught, making the cancer cell susceptible to oxidative therapies such as alpha lipoic acid.
eff↑, the addition of hydroxycitrate increases the effect of ALA.
PDKs↓, An inhibitory effect of lipoic acid on PDKs would result in… increased PDC pyruvate dehydrogenase complex (PDC) activity.

1627- HCA,    Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance
- Review, Var, NA
ChemoSen↑, short-term fasting or autophagy-inducing caloric restriction mimetics, such as hydroxycitrate and spermidine, improves the antitumor efficacy of chemotherapy in vivo
eff↑, combination of MTX and HC (but neither of these two agents alone) markedly reduced the frequency of tumor-infiltrating CD4+CD25+Foxp3+ Tregs
ACLY↓, HC acts as a competitive inhibitor of the ATP citrate lyase (ACLY)
LC3‑Ⅱ/LC3‑Ⅰ↑, ACLY inhibitors (SB-204990, BMS-303141) stimulated autophagic flux in cultured cancer cells, as indicated by the autophagy-associated conversion of LC3 I to LC3 II

1625- HCA,    In S. cerevisiae hydroxycitric acid antagonizes chronological aging and apoptosis regardless of citrate lyase
- Review, Nor, NA
CRM↑, Hydroxycitric acid (HCA) is considered a bona fide CRM since it depletes acetyl-CoA pools by acting as a competitive inhibitor of ATP citrate lyase (ACLY), ultimately repressing protein acetylation and promoting autophagy.
ACLY↓, competitive inhibitor of ATP citrate lyase (ACLY)
TumAuto↑, promoting autophagy.
Inflam↓, reduce inflammation and tumour development
TumCG↓,
toxicity∅, HCA appear to have a low or negligible impact in terms of acute or chronic toxicity, genotoxicity, reproductive failure and teratogenicity
lipoGen↓, decreases lipogenesis, insulin resistance, inflammation and oxidative stress
*ROS↓, H2O2 treatment: Strikingly, the molecule was able to largely prevent the massive cell death (PI+ cells) caused by the intense oxidative stress. In parallel there was a sharp increase of live cells with high ROS levels
*OCR↓, chronic exposure to 5 mM HCA (from cell seeding) down-regulated yeast OCR

1589- HCA,    ATP citrate lyase (ACLY) inhibitors: An anti-cancer strategy at the crossroads of glucose and lipid metabolism
- Review, NA, NA
ACLY↓, most well-known ACLY inhibitor is (‒)-hydroxycitric acid or (2S,3S)- 2-hydroxycitrate [59] (compound 1, HCA,
eff↑, HCA calcium salt with ALA ( METABLOC). ALA is a cofactor of the pyruvate dehydrogenase complex, a multi-enzymatic system linking glycolysis to Krebs cycle, since it promoted the transformation of pyruvate to acetyl-CoA

1415- HCA,    Hydroxycitrate delays early mortality in mice and promotes muscle regeneration while inducing a rich hepatic energetic status
- in-vivo, Nor, NA
*OS↑, mice treated with HC exhibited significant delays in spontaneous early mortality at 70%–90% mice survival in the longevity study
*toxicity↓, suggesting that chronic exposure to HC does not produce toxicity at the given dose
*AST∅, (AST) and ALT markers of liver damage were not altered
*ALAT∅,
*Strength↑, Remarkably, HC produced an increase in wire hang performance
*memory∅, HC did not produce remarkable effects in neurocognitive health and muscle strength in HFD‐fed mice
*other↑, HC promotes a rich energetic status in the liver
*other↑, HC potentiates muscle regeneration in vivo
*other↑, HC potentiates muscle regeneration in vivo

1413- HCA,    Effects of acute (-)-hydroxycitrate supplementation on substrate metabolism at rest and during exercise in humans
- Human, Nor, NA
*toxicity↓, Ten cyclists, 3.1 mL/kg body wt of an HCA solution (19 g/L) or placebo was ingested

1412- HCA,    Identification of ATP Citrate Lyase as a Positive Regulator of Glycolytic Function in Glioblastomas
- in-vitro, GBM, U87MG - in-vitro, GBM, LN229
ACLY↓, Inhibition of ACLY with hydroxycitrate suppressed (p < 0.05) in vitro glioblastoma cell migration, clonogenicity and brain invasion under glycolytic conditions and enhanced the suppressive effects of a Met inhibitor on cell migration.
TumCMig↓,

294- HCA,    In Vitro and In Vivo Toxicity of Garcinia or Hydroxycitric Acid: A Review

293- HCA,  Tam,    Hydroxycitric acid potentiates the cytotoxic effect of tamoxifen in MCF-7 breast cancer cells through inhibition of ATP citrate lyase
- in-vitro, BC, MCF-7
TumCG↓,
Apoptosis↑,
ACLY↓,
ACC-α↓,
Fas↓,

292- HCA,    Hydroxycitric Acid Inhibits Chronic Myelogenous Leukemia Growth through Activation of AMPK and mTOR Pathway
- in-vitro, AML, K562
ACLY↓,
AMPK↑,
mTOR↑,
eIF2α↑,
ATFs↑, ATF4
TumCG↓,

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↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 25

Results for Effect on Cancer/Diseased Cells:
ACC-α↓,1,   ACLY↓,10,   AMPK↑,1,   AMPK↝,1,   Apoptosis↑,1,   ATFs↑,1,   BAX↑,1,   Bcl-2↓,1,   Casp3↑,1,   ChemoSen↑,1,   CRM↑,1,   eff↓,1,   eff↑,4,   eIF2α↑,1,   Fas↓,1,   FASN↓,1,   Inflam↓,1,   LC3‑Ⅱ/LC3‑Ⅰ↑,1,   lipoGen↓,2,   mTOR↑,1,   OS↑,4,   other↓,1,   PDKs↓,1,   PI3K↝,1,   PSA↓,1,   ROS↑,1,   toxicity∅,1,   TumAuto↑,1,   TumCG↓,7,   TumCMig↓,1,   tumCV↓,1,   TumVol↓,1,   Weight↓,1,   Weight∅,1,  
Total Targets: 34

Results for Effect on Normal Cells:
ACLY↓,1,   ALAT∅,1,   Apoptosis↓,1,   AST∅,1,   BioAv↑,1,   Casp3↓,1,   Catalase↑,2,   Dose∅,1,   eff↑,2,   Hif1a↓,1,   HO-1↓,1,   IL6↓,1,   Inflam↓,2,   Iron↓,1,   MDA↓,2,   memory∅,1,   NF-kB↓,1,   NO↓,1,   NRF2↑,1,   OCR↓,1,   OS↑,1,   other↓,2,   other↑,4,   ROS↓,4,   SOD↓,1,   SOD↑,1,   Strength↑,1,   TNF-α↓,1,   toxicity↓,3,   toxicity∅,1,  
Total Targets: 30

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