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  1. #61
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    Got some triple strength with piperine (900mg per capsule). They are veggie caps.

    Any suggestion on dosages?

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    <div class='quotetop'>QUOTE (cam520 @ Aug 9 2010, 02:58 PM) <{POST_SNAPBACK}></div><div class='quotemain'>Got some triple strength with piperine (900mg per capsule). They are veggie caps.

    Any suggestion on dosages?</div>

    See forthcoming post for more information. To give you a general idea, doses used for anti-inflammatory and anti-cancer effects tend to be quite high, in the 1g-8g range PO. On the other hang, doses used for neurological effects are much, much lower -- more like 20mg/kg PO in mice, which is probably equivalent to about 300mg PO in a 75kg human. These are doses without piperine, too.

    BTW, if you're on any other pharmaceuticals, check them for CYP interactions. Piperine is one of the most wickedly strong CYP inhibitors known.

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    Excellent. Thanks.

    I took two tablets (1800mg), and will stick with one starting tomorrow with my daily supplements.

    Also purchased some NAC, DLPA and Vitamin D(3) as suggested by you and others.

    Much appreciated.

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    <div class='quotetop'>QUOTE (Ex Dubio @ Aug 10 2010, 12:14 AM) <{POST_SNAPBACK}></div><div class='quotemain'>See forthcoming post for more information. To give you a general idea, doses used for anti-inflammatory and anti-cancer effects tend to be quite high, in the 1g-8g range PO. On the other hang, doses used for neurological effects are much, much lower -- more like 20mg/kg PO in mice, which is probably equivalent to about 300mg PO in a 75kg human. These are doses without piperine, too.

    BTW, if you're on any other pharmaceuticals, check them for CYP interactions. Piperine is one of the most wickedly strong CYP inhibitors known.</div>
    just to complete that statement here is what a paper by Saxena et.al. (http://www.ncbi.nlm.nih.gov/pmc/arti...9/?tool=pubmed)^ has to say on the "CYP-effect" of piperine
    <div class='quotetop'>QUOTE </div><div class='quotemain'>Piperine from Piper (Piper nigrum)
    In clinical trials, piperine has shown to increase the bioavailability of phenytoin, propranolol and theophylline [23]. Although in vivo study on rat has demonstrated that piperine treatment suppressed CYP2E1 expression and enhanced 2B and 1A expression [12, 24]. It should be noted that the clinical observations are due for CYP isoforms for further research.</div>

    wikipedia has this to add:

    CYP2E1 = involved in the metabolism of xenobiotics in the body (also ethanol)
    CYP2B = involved with metabolizing nicotine, along with many other substances
    CYP1A = (1A1) involved in the metabolic activation of aromatic hydrocarbons; (1A2) xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen



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    Below is a compilation of the last month or two of research on curcumin. I simply cannot accurately convey how unbelievably complicated this compound in, but the following should answer almost any question you care to pose. The "Highly Notable" below is particularly worth reading, as it elucidates many of curcumin's properties. The "Caveats" section also contains most of the potential problems with curcumin use.

    In another post a bit later, I'll try to summarize my conclusions regarding its potential efficacy and risks in a few paragraphs. Dose is plays a huge role here, due to curcumin's homeotic properties, but there are also a lot of unknowns. Yet there's also a lot of potential. Though I don't have time to pursue this much any more, the big next step is fully understanding what the concentration of curcumin in the brain of mice and humans is and whether these concentration is sufficient to induce the toxic effects that curcumin is capable of. With normal dosing, it looks like curcumin will not reach nasty concentrations in the periphery, but the brain may be another matter due to curcumin's extreme lipophillicity.

    At any rate, I copy and pasted my little research document below.

    Highly Notable (Repeated Below)

    --- Reversed effects of chronic unpredictable stress, chronic treatment. (PMID: 19000708, 19302828, 17022948)
    --- MAO-A Inhibitor (PMID: 19000708, 18766332, 15987635)
    --- MAO-B Inhibitor (PMID: 9810264, 18408903, 18766332,15987635)
    --- NK-kappaB Inhibitor (PMID: 20188213, 20594343, 18368483, 10444409)
    --- Inhibits AR expression, at least in part by inhibiting AR co-activator beta-catenin. (PMID: 20680030, 12239622)
    --- Downregulates proinflammatory cytokines, including TNF, IL-1, IL-2, IL-6, IL-8, IL-12, and chemokines, primarily through inactivation of NF-kappaB. At low doses, however, can enhance antibody response. (PMID:17211725)
    --- Protects against glutamate excitotoxicity by inhibiting PKC and reducing glutamate-generated ROS as well as by increasing BDNF. (PMID: 17118359, 18420184)
    --- Shows anti-allergic properties, with a reduction of histamine release from mast cells. (PMID: 18398870)
    --- Attenuates CFS in murine water immersion stress model of CFS. Curcumin decreased lipid peroxidation, restored GSH, and attenuated immobility in immune-challenged fatigued mice. (PMID: 19159825)
    --- In a transgenic mouse model of AD, 24 mg/kg p.o. but not 750 mg/kg reduced oxidative damage and amyloid-beta deposition. (PMID: 16387899, 11606625)
    --- Commercial grade curcumin contains 10-20% curcuminoids, desmethoxycurcumin and bisdesmethoxycurcumin, and they are as effective as pure curcumin. (PMID: 18274631)
    --- Animals were given 500mg curcumin/kg body weight. Concentration was maximum in blood at 6 hours and remained elevated at 24 hours. 63.5% was absorbed. Only small proportion is excreted in urine. Bioavailability enhanced when administered with piperine. Intact curcumin was detected (after administration) in brain at 24, 48, and 96 h with a maximum at 48 h. (PMID: 20516541)
    --- Ongoing debate between Burgos-Moron et al. (PMID: 19830693, 20198619) and Kurien et al. (PMID: 20198612) regarding the potential of curcumin for DNA damage. Kurien et al. study seems of questionable merit.
    --- In rats treated with curcumin 10 or 20 mg/kg p.o. for 21 days (of restraint stress), plasma concentrations at the end were 55-120 ng/mL. (PMID: 19540859)
    --- Low concentrations (1 uM for 24 h) protect against cell death, whereas higher concentrations (more than 10 uM) induce cell apoptosis. (PMID: 19540859)
    --- Most adult Indians consume 80-200 mg curcumin per day. (PMID: 16387899)
    --- Doses as low as 10-20 mg/kg p.o. in rats have been used with good efficacy to reduce neurochemical effects of unpredictable chronic stress. (PMID: 17617388, 17022948)
    --- Dose-dependently induces chromosomal aberrations in mammalian cell lines at 10 ug/mL concentration. Studies indicate DNA damage and chromosomal abberations both in vitro and in vivo, and at similar concentrations to those with therapeutic benefit. (PMID: 19830693, 17132903, 16537656, 11585363, 15281237, 15790590, 12220536, 9500187, 2209081, 943364)
    --- Contains 2 alpha,beta-unsatured ketones in chemical structure, which are known to react covalently with exposed thiol groups of cysteine residues, possibly explaining irreversible modification of antioxidant thioredoxin reductase and topoisomerase II-mediated DNA damage, as well as inactivation of tumor-suppressor protein p53. (PMID: 19830693, 15879598, 15008515, 11258951, 15090465)

    Pharmacological Actions

    --- M1 Muscarinic Agonist (High affinity?) (PMID: 20172017)
    --- MAO-A Inhibitor (PMID: 19000708, 18766332, 15987635)
    --- MAO-B Inhibitor (PMID: 9810264, 18408903, 18766332,15987635)
    --- Antifungal (PMID: 20017731)
    --- Antibacterial (PMID: 20634977)
    --- Antiprotozoal (PMID: 19879924)
    --- NK-kappaB Inhibitor (PMID: 20188213, 20594343, 18368483, 10444409)
    --- TREK-1 K+ Channel Inhibitor (PMID: 18406348)
    --- TRPV1 Antagonist (PMID: 20040737)
    --- AChE Inhibitor (Not curcumin itself, but curcuminoids.) (PMID: 20026275, 18930076)
    --- CYP7A1 Inducer (PMID: 20607063)
    --- PPAR-gamma Activator (Not agonist.) (PMID: 20369229, 18274631)
    --- SIRT1 Activator (PMID: 20450879)
    --- AMPK Activator (PMID: 20561944)
    --- AR Inhibitor (PMID: 20680030, 12239622)
    --- Iron Chelator (PMID: 19830693, 18815282)
    --- Protonophoric Uncoupler (PMID: 19715674)
    --- mTOR Inhibitor (PMID: 19176385, 18790744, 16550606)

    Behavioral Effects

    --- Reduced immobility in FST, chronic treatment. (PMID: 16171853, 17942093, 15987635)
    --- Reduced immobility in tail suspension test, chronic treatment. (PMID: 15987635)
    --- Reversed olfactory bulbectomy-induced behavioral abnormalities, chronic treatment. (PMID: 16171853)
    --- Reversed effects of chronic unpredictable stress, chronic treatment. (PMID: 19000708, 19302828, 17022948)
    --- Ameliorates impaired cognition induced by chronic restraint stress. (PMID: 19540859)

    Endocrine Effects

    --- Inhibits ACTH- and AngII-stimulated cortisol secretion in bovine adrenal cells. (PMID: 19653644)
    --- Stimulates cortisol secretion from bovine adrenal cells via bTREK-1 K+ channel inhibition. (PMID: 18406348)
    --- Suppresses adipogenesis. (PMID: 20357182)
    --- Reduces cholesterol via upregulation of CYP7A1 (PMID: 20607063) and by increasing LDL-R. (PMID: 19879991)
    --- Induces phosphorylation of AMPK and increases glucose uptake in muscle cells, synergizing with insulin and increasing insulin sensitivity. (PMID: 20561944)
    --- Inhibits AR expression, at least in part by inhibiting AR co-activator beta-catenin. (PMID: 20680030, 12239622)
    --- Reduces PSA. (PMID: 20680030)
    --- Alters GR phosphorylation, but not clear how. (PMID: 18483179)

    Neurological Effects

    --- Abolished upregulation of BDNF transcription in response to morphine, along with morphine analgesic tolerance. (PMID: 19033880)
    --- Blocks capsaicin-induced TRPV1 activation and thereby inhibits TRPV1 pain hypersensitivity. (PMID: 20040737)
    --- Increases cortical BDNF and CREB. (PMID: 19879308)
    --- Elevates cellular GSH, enhacing astroglial efflux and neuroprotection. (PMID: 20437093)
    --- Shows in vitro, but not in vivo, AChE inhibitor potency, though other curcuminoids (which are likely present in commercial curcumin) show potent in vivo AChE inhibition. All curcuminoids, including curcumin, were effective at reducing scopolamine-induced amnesia. (PMID: 18930076)
    --- Beneficial effects in STZ-induced dementia are blocked by PPAR-gamma inhibition. (PMID: 20369229)
    --- Blocked production of NO, TNF-alpha, IL-1alpha, and IL-6 produced from LPS-stimulated microglia, but did not protect DA-directed neuronal cell death from SNP-induced NO generation. Neuroprotection may be mostly anti-inflammatory in nature. (PMID: 18214347)
    --- Induces expression of LRRK2 mRNA in rat mesencephalic cells. LRRK2 overexpression is strongly associated with neurodegenerative disorders, suggesting curcumin may have a negative effect. Did not change expression of other PD-risk genes, like alpha-synuclein. Also did not change expression of PD-protective parkin. (PMID: 19879924)
    --- Does not alter insulin receptor protein level or AChE activity in healthy rats, but only in memory-impaired rats. (PMID: 20026275)
    --- Inhibits MAO-A dose-dependently at low doses (~20mg/kg i.p. in mice) and inhibits MAO-B (not dose-dependently) at high doses (~80mg/kg i.p. in mice). Increases extracellular 5-HT and DA and synergizes in 5-HT elevation with antidepressants and in DA elevation with bupropion and selegeline. (PMID: 18766332)
    --- At 10-20 mg/kg p.o. in rats, reversed unpredictable chronic stress-induced BDNF decrease accross all hippoampal subfields and reversed 5-HT1A mRNA reduction in CA1 and DG. (PMID: 17617388)
    --- At 5-20 mg/kg p.o. in rats, alleviated stress-induced physiological changes in the adrenal cortex, increase in serum CORT, decrease in hippocampal GR mRNA, and decrease in pCREB/CREB ratio and BDNF in the hippocampus, in line with the effects of imipramine and fluoxetine. (PMID: 17022948)
    --- 5-HT1A agonism and 5-HT2C antagonism synergize with curcumin in the antidepressant FST test. 5-HT1A/1B and 5-HT1B antagonists block this effects of curcumin. (PMID: 17942093)
    --- Synergizes with iNOS inhibitors to produce anxiolysis, but not with nNOS inhibitors. (PMID: 20633542)
    --- Increased 5-HT and NE in frontal cortex and hippocampus and DA in the frontal cortex and striatum. DA was increased to 150% of baseline with 10 mg/kg p.o. in mice. (PMID: 15987635)
    --- Reverses CORT-induced (i.e. stress-induced) increase in phosphorylated CaMKII and NMDAR2B. (PMID: 19540859)
    --- In a chronic unpredictable stress paradigm, hippocampal and hypothalmus 5-HT1A and 5-HT7 mRNA were upregulated, and 30 mg/kg curcumin p.o. and 7 mg/kg fluoxetine p.o. reversed these effects. They likewise reversed elevated 5-HT1A mRNA in the cortex. Curcumin 15 mg/kg, but not fluoxetine, suppressed stress-induced 5-HT1B mRNA in the hypothalamus. (PMID: 19302828)
    --- At 30 mg/kg p.o., reversed chronic unpredictable stress-induced decrease in adenylyl cyclase, cAMP, and CREB activity in hippocampus, cortex, and hypothalamus. (PMID: 19302828)

    Immunological Effects

    --- Inhibits IL-1beta induecd NF-kappaB signaling in mesenchymal stem cell progenitors in articular cartiliage, possibly faciliating chondrogenesis and regenerating cartilage. (PMID: 20594343)
    --- Enhances pathogenicity of salmonella enterica by increasing resistance against antimicrobial agents. (PMID: 20634977)
    --- Has antibacterial action against S. aureus, E. coli, S. lutea, B. subtilis, and H. pylori. (PMID: 20634977)
    --- Protects bacteria S. typhimurium (TA1535/pSK1002), E. coli (K-12), E. coli, B. megaterium, and B. pumilus against DNA inactivation and/or mutagenesis. (PMID: 20634977)
    --- Reduces dyspepsia induced by H. pylori without reducing H. pylori burden. (PMID: 19879991)
    --- Inhibits phagocytic activity while decreasing ROI and RNI, potentially increasing vulnerability to infectious organisms that are vulnerable to ROS and able to enter cells via phagocytosis. (PMID: 19879991)
    --- Inhibits antigen presentation capacity of dendritic cells, which may be advantageous in autoimmune disease, but disadvantageous otherwise. (PMID: 19879991)
    --- Inhibits IL-12 and IFN production by activated CD4+ T cells. (PMID: 19879991)
    --- Downregulates proinflammatory cytokines, including TNF, IL-1, IL-2, IL-6, IL-8, IL-12, and chemokines, primarily through inactivation of NF-kappaB. At low doses, however, can enhance antibody response. (PMID:17211725)
    --- Activates Nrf/ARE signaling pathway to activate antioxidant enzymes including heme oxygenase, Hsp70, thioredoxin reductase, and sirtuins. (PMID: 20205886)
    --- Inhibits TGF-beta and fibrogenesis. (PMID: 16387899)

    Therapeutic Effects

    --- Exerts hepatoprotective properties against ethanol via HO-1 induction. (PMID: 20080166)
    --- Reduces glial activation and cerebral edema following neurotrauma. (PMID: 20132469)
    --- Suppresses inflammatory response in collagen-induced arthritis model by altering NF-kappaB and inhibiting PGE-2, COX-2, and MMP. (PMID: 20188213)
    --- Inhibits neuropathic pain by inhibiting NO and TNF-alpha release. (PMID: 16584726)
    --- Exerts neuroprotective effects in spinal cord injury by increasing tissue GSH-Px, SOD, and CAT. (PMID: 20535508)
    --- Improves muscular insulin resistance in diabetic rats by increasing oxidation of fatty acid and gluocose, in part mediated by LKB1-AMPK pathway. (PMID: 20227862)
    --- Reduces diabetes-induced alteration in D1/D2 and CREB signaling in cerebral cortex and cerebellum in rats. (PMID: 20513244)
    --- Prevents cataract development by interfering with free radical-mediated Ca2+ accumulation. (PMID: 19932168)
    --- Has therapeutic potential in dry eye disease. (PMID: 20026325)
    --- Reduces LPS-induced NF-kappaB and DA neurotoxicity. (PMID: 18368483)
    --- Protects against infection-driven white matter injury. (PMID: 20403340)
    --- Enhances IL-10 and suppresses p38 MAPK, IL-1beta, and MMP-3 in inflammatory bowel disease. (PMID: 19878610)
    --- Exhibits antiallergic activity via Syk kinase-dependent signaling. (PMID: 18394691)
    --- Reduces cognitive impairment in TBI via reduction of oxidative stress. (PMID: 16364299)
    --- Protects against glutamate excitotoxicity by inhibiting PKC and reducing glutamate-generated ROS as well as by increasing BDNF. (PMID: 17118359, 18420184)
    --- Protects against STZ-inded dementia by reduction of AChE activity and increasing insulin receptor protein level, but does not alter AChE or IR in healthy rats. (PMID: 20026275)
    --- Reverses MPTP-induced DA depletion, at least in part by MAO-B inhibition. (PMID: 18408903)
    --- Inhibits colonic inflammation by inhibition of chemokine expression and neutrophil chemotaxis/chemokinesis. (PMID: 20629184)
    --- Prevented weight loss, impairment of locomotor activity, and anxiety in sleep-deprived mice. Also restored glutathione and catalase. Effects mediated through NO modulation. (PMID: 18586477)
    --- Reversed COX-2 enhancement, PPAR-gamma inhibition, and NF-kappaB translocation induced by amyloid beta in astrocytes. Effects blocked by PPAR-gamma antagonist. (PMID: 20413894)
    --- Inhibits neuroleptic-induced orofacial dyskinesia, apparently by reducion in ROS. (PMID: 18022680)
    --- Stimulates cell proliferation and differentiation of muscle cells, primarily by blocking NF-kappaB. (PMID: 10444409)
    --- Shows anti-allergic properties, with a reduction of histamine release from mast cells. (PMID: 18398870)
    --- Augments endogenous antioxidant systems and preserves myocardial architecture at low (100-200 mg/kg) doses, but medaites ROS induction and myocardial damage at higher (400 mg/kg) concentrations, in a rat model of myocardial necrosis. (PMID: 20029958)
    --- Partially restored daily 5-HT/5-HIIA ratio, with phase shifts in SCN and pineal, in ethanol-withdrawn rats under light/dark conditions. (PMID: 17846884)
    --- Attenuates CFS in murine water immersion stress model of CFS. Curcumin decreased lipid peroxidation, restored GSH, and attenuated immobility in immune-challenged fatigued mice. (PMID: 19159825)
    --- Attenuates amyloid-beta-induced cognitive deficits. (PMID: 11755008)
    --- Protects against ethanol-induced brain damage (PMID: 10548748)
    --- May prevent atherosclerosis by inhibiting lipid peroxidation, stabilizing cellular membranes, inhibitng proliferation of vascular smooth muscle cells, and inhibitng platelet aggregation. (PMID: 16387899)
    --- In a transgenic mouse model of AD, 24 mg/kg p.o. but not 750 mg/kg reduced oxidative damage and amyloid-beta deposition. (PMID: 16387899, 11606625)

    Important Notes

    --- Potent inhibitor of rat CYP1A1/1A2, less potent inhibitor of 2B1/2B2, and weak inhibitor of 2E1. Shows competetive inhibition. (PMID: 8534266, 11346483)
    --- Inhibited CYP1A2 (IC50 40 uM), CYP3A4 (IC50 16.3 uM), CYP2D6 (IC50 50.3 uM), CYP2C9 (IC50 4.3 uM), and CYP2B6 (IC50 24.5 uM). Competetive inhibition toward 1A2, 3A4, and 2B6. Non-competetive toward 2D6 and 2C9. However, the liver typically has low exposure to curcumin. (PMID: 17433521)
    --- Potent inhibitor of glutathione S-transferase. (PMID: 8534266)
    --- Shockingly, acts as an uncoupling agent like DNP. (PMID: 19715674)
    --- Inhibits COX-2, LOX-2, xanthine dehydrogenase/oxidase, iNOS, PKC, EGF-receptor tyrosine kinase, IkappaB kinase, NF-kappaB, c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs, and mTOR while inducing HO-1. (PMID: 17569214)
    --- Ongoing debate between Burgos-Moron et al. (PMID: 19830693, 20198619) and Kurien et al. (PMID: 20198612) regarding the potential of curcumin for DNA damage. Kurien et al. study seems of questionable merit.
    --- Molecular targets include AP-1, SP-1, p53, STAT-3, ATF3, Nrf2, PPAR-gamma, CHOP, HIF1alpha, beta-catenin, and NF-kappaB, as well as enzymes like PKA, PKC, FAK, Src, glutathione S-transferase, DNA topoisomerase-II, telomerase, HO-1, p300 histone acetyltransferase, metaloproteinases, 5-LOX, COX-2, and yet more. (PMID: 20205886)
    --- Age-adjusted incidence of cancers and incidence of AD and PD in India is lower than that in Western countires. Incidence of AD is 4.4-fold lower. (PMID: 16387899,19879924, 20205886)

    Dose and Concentration

    --- Commercial grade curcumin contains 10-20% curcuminoids, desmethoxycurcumin and bisdesmethoxycurcumin, and they are as effective as pure curcumin. It also contains 79-85% curcumin. (PMID: 18274631,19830693)
    --- Animals were given 500mg curcumin/kg body weight. Concentration was maximum in blood at 6 hours and remained elevated at 24 hours. 63.5% was absorbed. Only small proportion is excreted in urine. Bioavailability enhanced when administered with piperine. Intact curcumin was detected (after administration) in brain at 24, 48, and 96 h with a maximum at 48 h. (PMID: 20516541)
    --- Curcumin undergoes extensive metabolic conjugation and reduction in the GI tract and there is more metabolism in human than rat intenstinal tissue. (PMID: 1181540)
    --- In rats treated with curcumin 10 or 20 mg/kg p.o. for 21 days (of restraint stress), plasma concentrations at the end were 55-120 ng/mL. (PMID: 19540859)
    --- Effective in neurological diseases, like AD and depression, with optimum doss of 2.5-25 mg/kg body weight (in mice).
    --- Low concentrations (1 uM for 24 h) protect against cell death, whereas higher concentrations (more than 10 uM) induce cell apoptosis. (PMID: 19540859)
    --- Should not display a "cheese reaction". Given baseline levels of 50 nmol/30 min/mg MAO-A and 236.7 nmom/30 min/mg MAO-B, curcumin p.o. in mice at doses of 1.25 mg/kg, 2.5 mg/kg, 5 mg/kg, and 10 mg/kg reduced these to (44.3, 230.7), (36.4, 210.2), (35.6, 201.6), (34.8,169.2), given as (MAO-A, MAO-[img]style_emoticons/<#EMO_DIR#>/cool.gif[/img]. (PMID: 15987635)
    --- In a transgenic mouse model of AD, 24 mg/kg p.o. but not 750 mg/kg reduced oxidative damage and amyloid-beta deposition. (PMID: 16387899, 11606625)
    --- At 5-20 mg/kg p.o. in rats, reversed escape deficits in footshock avoidance induced by chronic unpredictable mild stress with chroinc treatment. (PMID: 17022948)
    --- At 10-20 mg/kg p.o. in rats, reversed unpredictable chronic stress-induced BDNF decrease accross all hippoampal subfields and reversed 5-HT1A mRNA reduction in CA1 and DG. (PMID: 17617388)
    --- At 5-20 mg/kg p.o. in rats, alleviated stress-induced physiological changes in the adrenal cortex, increase in serum CORT, decrease in hippocampal GR mRNA, and decrease in pCREB/CREB ratio and BDNF in the hippocampus, in line with the effects of imipramine and fluoxetine. (PMID: 17022948)
    --- At 30 mg/kg p.o., reversed chronic unpredictable stress-induced decrease in adenylyl cyclase, cAMP, and CREB activity in hippocampus, cortex, and hypothalamus. (PMID: 19302828)
    --- In a chronic unpredictable stress paradigm, hippocampal and hypothalmus 5-HT1A and 5-HT7 mRNA were upregulated, and 30 mg/kg curcumin p.o. and 7 mg/kg fluoxetine p.o. reversed these effects. They likewise reversed elevated 5-HT1A mRNA in the cortex. Curcumin 15 mg/kg, but not fluoxetine, suppressed stress-induced 5-HT1B mRNA in the hypothalamus. (PMID: 19302828)
    --- Increased 5-HT and NE in frontal cortex and hippocampus and DA in the frontal cortex and striatum. DA was increased to 150% of baseline with 10 mg/kg p.o. in mice. (PMID: 15987635)
    --- Doses as low as 10-20 mg/kg p.o. in rats have been used with good efficacy to reduce neurochemical effects of unpredictable chronic stress. (PMID: 17617388, 17022948)
    --- Plasma concentrations of curcumin in people taking high oral doses are usually in the nanomolar range. (PMID: 19830693, 18559556)
    --- In terms of brain monoamines, piperine (2.5mg/kg i.p. in mice) changed the effects of curcumin 20mg/kg i.p. to resemble those of curcumin 40mg/kg i.p. (PMID: 18766332)
    --- Does not cause short-term toxicity at doses up to 8g/day for 3 months.
    --- Most adult Indians consume 80-200 mg curcumin per day. (PMID: 16387899)

    Caveats

    --- Curcumin delays and partially inhibits meiotic resumption of oocytes and inhibits meiotic and mitotic divisions by disrupting spindle structure and inhibiting CDK1, without inducing DNA damage. Curcumin thereby impairs generative and somatic cell division, with potential side effects of normal cells. (PMID: 20590660)
    --- Inhibits AR expression. (PMID: 20680030, 12239622)
    --- Enhances pathogenicity of salmonella enterica by increasing resistance against antimicrobial agents. (PMID: 20634977)
    --- Protects bacteria S. typhimurium (TA1535/pSK1002), E. coli (K-12), E. coli, B. megaterium, and B. pumilus against DNA inactivation and/or mutagenesis. (PMID: 20634977)
    --- Induces expression of LRRK2 mRNA in rat mesencephalic cells. LRRK2 overexpression is strongly associated with neurodegenerative disorders, suggesting curcumin may have a negative effect. Did not change expression of other PD-risk genes, like alpha-synuclein. Also did not change expression of PD-protective parkin. (PMID: 19879924)
    --- Augments endogenous antioxidant systems and preserves myocardial architecture at low (100-200 mg/kg) doses, but medaites ROS induction and myocardial damage at higher (400 mg/kg) concentrations, in a rat model of myocardial necrosis. (PMID: 20029958, 19830693)
    --- Inhibits phagocytic activity while decreasing ROI and RNI, potentially increasing vulnerability to infectious organisms that are vulnerable to ROS and able to enter cells via phagocytosis. (PMID: 19879991)
    --- Inhibits antigen presentation capacity of dendritic cells, which may be advantageous in autoimmune disease, but disadvantageous otherwise. (PMID: 19879991)
    --- Inhibits IL-12 and IFN production by activated CD4+ T cells. (PMID: 19879991)
    --- Dose-dependently induces chromosomal aberrations in mammalian cell lines at 10 ug/mL concentration. Studies indicate DNA damage and chromosomal abberations both in vitro and in vivo, and at similar concentrations to those with therapeutic benefit. (PMID: 19830693, 17132903, 16537656, 11585363, 15281237, 15790590, 12220536, 9500187, 2209081, 943364)
    --- Rats and mice fed curcumin for 2 years saw increased rates of ulcers, hyperplasia, stomach inflammation, and cancers of the liver and intestine. (PMID: 19830693, 12616304)
    --- Curcumin may promote lung cancer in mice. (PMID: 19830693, 19359593)
    --- Contains 2 alpha,beta-unsatured ketones in chemical structure, which are known to react covalently with exposed thiol groups of cysteine residues, possibly explaining irreversible modification of antioxidant thioredoxin reductase and topoisomerase II-mediated DNA damage, as well as inactivation of tumor-suppressor protein p53. (PMID: 19830693, 15879598, 15008515, 11258951, 15090465)
    --- Iron chelation activity induced iron deficiency anemia in mice fed iron-poor diets. (PMID: 19830693)
    --- At doses of 0.9-3.6 g/day for 1-4 months, increased incidence of nausea and diarrhea as well as serum alkaline phosphatase and lactate dehydrogenase in humans. (PMID: 19830693)
    --- Long-term, low-dose (< 5mg/week) curcumin in mice activates PPARgamma, deactives type 1 response, inhibits iNOS, and interferes with adaptive immunity to exacerbate pathogenesis of Leishmania donovani parasitic disease. When reactive radicals from inflammation play dominant role in pathogen elimination, antioxidant supplements may compromise mocrobial defense. But curcmin may alleviate type 1 disorders. (PMID: 18794851)
    --- Has failed to show efficacy in Alzheimer's disease and cardiovascular diseases. (PMID: 19830693)

    --- Suppresses inflammatory response in collagen-induced arthritis model by altering NF-kappaB and inhibiting PGE-2, COX-2, and MMP. (PMID: 20188213)
    --- Inhibits neuropathic pain by inhibiting NO and TNF-alpha release. (PMID: 16584726)


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    If Indians are any indication of curcumins effects, building up over generations, I think I'll pass.

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    Thanks for putting this together.

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    After seeing a compilation like this I think I'm more interested in how Ex Dubio can process this amount of information, than the actual info on curcumin [img]style_emoticons/<#EMO_DIR#>/wink.gif[/img]

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    <div class='quotetop'>QUOTE (adrenoguy @ Aug 11 2010, 12:49 PM) <{POST_SNAPBACK}></div><div class='quotemain'>After seeing a compilation like this I think I'm more interested in how Ex Dubio can process this amount of information, than the actual info on curcumin [img]style_emoticons/<#EMO_DIR#>/wink.gif[/img]</div>

    He's a machine from the future, sent back through time for a singular purpose: to explain the intricacies of neuroscience and pharmacological/supplemental interventions to 21st century mortals. Like Terminator except with pubmed on his heads-up display.

    He woke up naked in a parking lot somewhere with a prescription for an SSRI in one hand, dextroamphetamine in the other. lol
    "Also, can I rig some sort of enema out of household items?" -Tussman

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    <div class='quotetop'>QUOTE (FunkOdyssey @ Aug 11 2010, 10:10 AM) <{POST_SNAPBACK}></div><div class='quotemain'>He's a machine from the future, sent back through time for a singular purpose: to explain the intricacies of neuroscience and pharmacological/supplemental interventions to 21st century mortals. Like Terminator except with pubmed on his heads-up display.

    He woke up naked in a parking lot somewhere with a prescription for an SSRI in one hand, dextroamphetamine in the other. lol</div>

    lol! Sounds about right.

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    Too bad these trials weren't done on humans only, but good job Ex Dubio!
    Btw. turmeric is a bad choice if your adrenals are overactive. From my experience, it's a sleep wrecker (once I took 10g with my last meal, 2h before bed).

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    *<div class='quotetop'>QUOTE (FunkOdyssey @ Aug 11 2010, 01:10 PM) <{POST_SNAPBACK}></div><div class='quotemain'>He woke up naked in a parking lot somewhere with a prescription for an SSRI in one hand, dextroamphetamine in the other. lol</div>
    Ahahahahahahahahahaha! Priceless!



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    <div class='quotetop'>QUOTE (FunkOdyssey @ Aug 11 2010, 10:10 AM) <{POST_SNAPBACK}></div><div class='quotemain'>He woke up naked in a parking lot somewhere with a prescription for an SSRI in one hand, dextroamphetamine in the other. lol</div>

    You are not privileged to this information. Prepare for termination.

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    <div class='quotetop'>QUOTE (FunkOdyssey @ Aug 11 2010, 01:10 PM) <{POST_SNAPBACK}></div><div class='quotemain'>He's a machine from the future, sent back through time for a singular purpose: to explain the intricacies of neuroscience and pharmacological/supplemental interventions to 21st century mortals. Like Terminator except with pubmed on his heads-up display.

    He woke up naked in a parking lot somewhere with a prescription for an SSRI in one hand, dextroamphetamine in the other. lol</div>
    hahaha nice! [img]style_emoticons/<#EMO_DIR#>/laugh.gif[/img]
    One
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    I took 500mg with dinner last night, about 1-2 hours after working out. I felt very relaxed and at ease when I finally got into bed - possibly just in my head. Today I'm feeling good, joint/muscle pain isn't as bad. I'll have to see how this goes, as it's only been a day.



    What's the half-life on this stuff? Knowing this would help zero in on the optimal time(s) to take it WRT to training.


    If someone says something about you, and it really bothers you, it's probably because it's true.

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    Quote Originally Posted by Ex Dubio View Post
    Below is a compilation of the last month or two of research on curcumin. I simply cannot accurately convey how unbelievably complicated this compound in, but the following should answer almost any question you care to pose. The "Highly Notable" below is particularly worth reading, as it elucidates many of curcumin's properties. The "Caveats" section also contains most of the potential problems with curcumin use.



    In another post a bit later, I'll try to summarize my conclusions regarding its potential efficacy and risks in a few paragraphs. Dose is plays a huge role here, due to curcumin's homeotic properties, but there are also a lot of unknowns. Yet there's also a lot of potential. Though I don't have time to pursue this much any more, the big next step is fully understanding what the concentration of curcumin in the brain of mice and humans is and whether these concentration is sufficient to induce the toxic effects that curcumin is capable of. With normal dosing, it looks like curcumin will not reach nasty concentrations in the periphery, but the brain may be another matter due to curcumin's extreme lipophillicity.



    At any rate, I copy and pasted my little research document below.



    Highly Notable (Repeated Below)



    --- Reversed effects of chronic unpredictable stress, chronic treatment. (PMID: 19000708, 19302828, 17022948)

    --- MAO-A Inhibitor (PMID: 19000708, 18766332, 15987635)

    --- MAO-B Inhibitor (PMID: 9810264, 18408903, 18766332,15987635)

    --- NK-kappaB Inhibitor (PMID: 20188213, 20594343, 18368483, 10444409)

    --- Inhibits AR expression, at least in part by inhibiting AR co-activator beta-catenin. (PMID: 20680030, 12239622)

    --- Downregulates proinflammatory cytokines, including TNF, IL-1, IL-2, IL-6, IL-8, IL-12, and chemokines, primarily through inactivation of NF-kappaB. At low doses, however, can enhance antibody response. (PMID:17211725)

    --- Protects against glutamate excitotoxicity by inhibiting PKC and reducing glutamate-generated ROS as well as by increasing BDNF. (PMID: 17118359, 18420184)

    --- Shows anti-allergic properties, with a reduction of histamine release from mast cells. (PMID: 18398870)

    --- Attenuates CFS in murine water immersion stress model of CFS. Curcumin decreased lipid peroxidation, restored GSH, and attenuated immobility in immune-challenged fatigued mice. (PMID: 19159825)

    --- In a transgenic mouse model of AD, 24 mg/kg p.o. but not 750 mg/kg reduced oxidative damage and amyloid-beta deposition. (PMID: 16387899, 11606625)

    --- Commercial grade curcumin contains 10-20% curcuminoids, desmethoxycurcumin and bisdesmethoxycurcumin, and they are as effective as pure curcumin. (PMID: 18274631)

    --- Animals were given 500mg curcumin/kg body weight. Concentration was maximum in blood at 6 hours and remained elevated at 24 hours. 63.5% was absorbed. Only small proportion is excreted in urine. Bioavailability enhanced when administered with piperine. Intact curcumin was detected (after administration) in brain at 24, 48, and 96 h with a maximum at 48 h. (PMID: 20516541)

    --- Ongoing debate between Burgos-Moron et al. (PMID: 19830693, 20198619) and Kurien et al. (PMID: 20198612) regarding the potential of curcumin for DNA damage. Kurien et al. study seems of questionable merit.

    --- In rats treated with curcumin 10 or 20 mg/kg p.o. for 21 days (of restraint stress), plasma concentrations at the end were 55-120 ng/mL. (PMID: 19540859)

    --- Low concentrations (1 uM for 24 h) protect against cell death, whereas higher concentrations (more than 10 uM) induce cell apoptosis. (PMID: 19540859)

    --- Most adult Indians consume 80-200 mg curcumin per day. (PMID: 16387899)

    --- Doses as low as 10-20 mg/kg p.o. in rats have been used with good efficacy to reduce neurochemical effects of unpredictable chronic stress. (PMID: 17617388, 17022948)

    --- Dose-dependently induces chromosomal aberrations in mammalian cell lines at 10 ug/mL concentration. Studies indicate DNA damage and chromosomal abberations both in vitro and in vivo, and at similar concentrations to those with therapeutic benefit. (PMID: 19830693, 17132903, 16537656, 11585363, 15281237, 15790590, 12220536, 9500187, 2209081, 943364)

    --- Contains 2 alpha,beta-unsatured ketones in chemical structure, which are known to react covalently with exposed thiol groups of cysteine residues, possibly explaining irreversible modification of antioxidant thioredoxin reductase and topoisomerase II-mediated DNA damage, as well as inactivation of tumor-suppressor protein p53. (PMID: 19830693, 15879598, 15008515, 11258951, 15090465)



    Pharmacological Actions



    --- M1 Muscarinic Agonist (High affinity?) (PMID: 20172017)

    --- MAO-A Inhibitor (PMID: 19000708, 18766332, 15987635)

    --- MAO-B Inhibitor (PMID: 9810264, 18408903, 18766332,15987635)

    --- Antifungal (PMID: 20017731)

    --- Antibacterial (PMID: 20634977)

    --- Antiprotozoal (PMID: 19879924)

    --- NK-kappaB Inhibitor (PMID: 20188213, 20594343, 18368483, 10444409)

    --- TREK-1 K+ Channel Inhibitor (PMID: 18406348)

    --- TRPV1 Antagonist (PMID: 20040737)

    --- AChE Inhibitor (Not curcumin itself, but curcuminoids.) (PMID: 20026275, 18930076)

    --- CYP7A1 Inducer (PMID: 20607063)

    --- PPAR-gamma Activator (Not agonist.) (PMID: 20369229, 18274631)

    --- SIRT1 Activator (PMID: 20450879)

    --- AMPK Activator (PMID: 20561944)

    --- AR Inhibitor (PMID: 20680030, 12239622)

    --- Iron Chelator (PMID: 19830693, 18815282)

    --- Protonophoric Uncoupler (PMID: 19715674)

    --- mTOR Inhibitor (PMID: 19176385, 18790744, 16550606)



    Behavioral Effects



    --- Reduced immobility in FST, chronic treatment. (PMID: 16171853, 17942093, 15987635)

    --- Reduced immobility in tail suspension test, chronic treatment. (PMID: 15987635)

    --- Reversed olfactory bulbectomy-induced behavioral abnormalities, chronic treatment. (PMID: 16171853)

    --- Reversed effects of chronic unpredictable stress, chronic treatment. (PMID: 19000708, 19302828, 17022948)

    --- Ameliorates impaired cognition induced by chronic restraint stress. (PMID: 19540859)



    Endocrine Effects



    --- Inhibits ACTH- and AngII-stimulated cortisol secretion in bovine adrenal cells. (PMID: 19653644)

    --- Stimulates cortisol secretion from bovine adrenal cells via bTREK-1 K+ channel inhibition. (PMID: 18406348)

    --- Suppresses adipogenesis. (PMID: 20357182)

    --- Reduces cholesterol via upregulation of CYP7A1 (PMID: 20607063) and by increasing LDL-R. (PMID: 19879991)

    --- Induces phosphorylation of AMPK and increases glucose uptake in muscle cells, synergizing with insulin and increasing insulin sensitivity. (PMID: 20561944)

    --- Inhibits AR expression, at least in part by inhibiting AR co-activator beta-catenin. (PMID: 20680030, 12239622)

    --- Reduces PSA. (PMID: 20680030)

    --- Alters GR phosphorylation, but not clear how. (PMID: 18483179)



    Neurological Effects



    --- Abolished upregulation of BDNF transcription in response to morphine, along with morphine analgesic tolerance. (PMID: 19033880)

    --- Blocks capsaicin-induced TRPV1 activation and thereby inhibits TRPV1 pain hypersensitivity. (PMID: 20040737)

    --- Increases cortical BDNF and CREB. (PMID: 19879308)

    --- Elevates cellular GSH, enhacing astroglial efflux and neuroprotection. (PMID: 20437093)

    --- Shows in vitro, but not in vivo, AChE inhibitor potency, though other curcuminoids (which are likely present in commercial curcumin) show potent in vivo AChE inhibition. All curcuminoids, including curcumin, were effective at reducing scopolamine-induced amnesia. (PMID: 18930076)

    --- Beneficial effects in STZ-induced dementia are blocked by PPAR-gamma inhibition. (PMID: 20369229)

    --- Blocked production of NO, TNF-alpha, IL-1alpha, and IL-6 produced from LPS-stimulated microglia, but did not protect DA-directed neuronal cell death from SNP-induced NO generation. Neuroprotection may be mostly anti-inflammatory in nature. (PMID: 18214347)

    --- Induces expression of LRRK2 mRNA in rat mesencephalic cells. LRRK2 overexpression is strongly associated with neurodegenerative disorders, suggesting curcumin may have a negative effect. Did not change expression of other PD-risk genes, like alpha-synuclein. Also did not change expression of PD-protective parkin. (PMID: 19879924)

    --- Does not alter insulin receptor protein level or AChE activity in healthy rats, but only in memory-impaired rats. (PMID: 20026275)

    --- Inhibits MAO-A dose-dependently at low doses (~20mg/kg i.p. in mice) and inhibits MAO-B (not dose-dependently) at high doses (~80mg/kg i.p. in mice). Increases extracellular 5-HT and DA and synergizes in 5-HT elevation with antidepressants and in DA elevation with bupropion and selegeline. (PMID: 18766332)

    --- At 10-20 mg/kg p.o. in rats, reversed unpredictable chronic stress-induced BDNF decrease accross all hippoampal subfields and reversed 5-HT1A mRNA reduction in CA1 and DG. (PMID: 17617388)

    --- At 5-20 mg/kg p.o. in rats, alleviated stress-induced physiological changes in the adrenal cortex, increase in serum CORT, decrease in hippocampal GR mRNA, and decrease in pCREB/CREB ratio and BDNF in the hippocampus, in line with the effects of imipramine and fluoxetine. (PMID: 17022948)

    --- 5-HT1A agonism and 5-HT2C antagonism synergize with curcumin in the antidepressant FST test. 5-HT1A/1B and 5-HT1B antagonists block this effects of curcumin. (PMID: 17942093)

    --- Synergizes with iNOS inhibitors to produce anxiolysis, but not with nNOS inhibitors. (PMID: 20633542)

    --- Increased 5-HT and NE in frontal cortex and hippocampus and DA in the frontal cortex and striatum. DA was increased to 150% of baseline with 10 mg/kg p.o. in mice. (PMID: 15987635)

    --- Reverses CORT-induced (i.e. stress-induced) increase in phosphorylated CaMKII and NMDAR2B. (PMID: 19540859)

    --- In a chronic unpredictable stress paradigm, hippocampal and hypothalmus 5-HT1A and 5-HT7 mRNA were upregulated, and 30 mg/kg curcumin p.o. and 7 mg/kg fluoxetine p.o. reversed these effects. They likewise reversed elevated 5-HT1A mRNA in the cortex. Curcumin 15 mg/kg, but not fluoxetine, suppressed stress-induced 5-HT1B mRNA in the hypothalamus. (PMID: 19302828)

    --- At 30 mg/kg p.o., reversed chronic unpredictable stress-induced decrease in adenylyl cyclase, cAMP, and CREB activity in hippocampus, cortex, and hypothalamus. (PMID: 19302828)



    Immunological Effects



    --- Inhibits IL-1beta induecd NF-kappaB signaling in mesenchymal stem cell progenitors in articular cartiliage, possibly faciliating chondrogenesis and regenerating cartilage. (PMID: 20594343)

    --- Enhances pathogenicity of salmonella enterica by increasing resistance against antimicrobial agents. (PMID: 20634977)

    --- Has antibacterial action against S. aureus, E. coli, S. lutea, B. subtilis, and H. pylori. (PMID: 20634977)

    --- Protects bacteria S. typhimurium (TA1535/pSK1002), E. coli (K-12), E. coli, B. megaterium, and B. pumilus against DNA inactivation and/or mutagenesis. (PMID: 20634977)

    --- Reduces dyspepsia induced by H. pylori without reducing H. pylori burden. (PMID: 19879991)

    --- Inhibits phagocytic activity while decreasing ROI and RNI, potentially increasing vulnerability to infectious organisms that are vulnerable to ROS and able to enter cells via phagocytosis. (PMID: 19879991)

    --- Inhibits antigen presentation capacity of dendritic cells, which may be advantageous in autoimmune disease, but disadvantageous otherwise. (PMID: 19879991)

    --- Inhibits IL-12 and IFN production by activated CD4+ T cells. (PMID: 19879991)

    --- Downregulates proinflammatory cytokines, including TNF, IL-1, IL-2, IL-6, IL-8, IL-12, and chemokines, primarily through inactivation of NF-kappaB. At low doses, however, can enhance antibody response. (PMID:17211725)

    --- Activates Nrf/ARE signaling pathway to activate antioxidant enzymes including heme oxygenase, Hsp70, thioredoxin reductase, and sirtuins. (PMID: 20205886)

    --- Inhibits TGF-beta and fibrogenesis. (PMID: 16387899)



    Therapeutic Effects



    --- Exerts hepatoprotective properties against ethanol via HO-1 induction. (PMID: 20080166)

    --- Reduces glial activation and cerebral edema following neurotrauma. (PMID: 20132469)

    --- Suppresses inflammatory response in collagen-induced arthritis model by altering NF-kappaB and inhibiting PGE-2, COX-2, and MMP. (PMID: 20188213)

    --- Inhibits neuropathic pain by inhibiting NO and TNF-alpha release. (PMID: 16584726)

    --- Exerts neuroprotective effects in spinal cord injury by increasing tissue GSH-Px, SOD, and CAT. (PMID: 20535508)

    --- Improves muscular insulin resistance in diabetic rats by increasing oxidation of fatty acid and gluocose, in part mediated by LKB1-AMPK pathway. (PMID: 20227862)

    --- Reduces diabetes-induced alteration in D1/D2 and CREB signaling in cerebral cortex and cerebellum in rats. (PMID: 20513244)

    --- Prevents cataract development by interfering with free radical-mediated Ca2+ accumulation. (PMID: 19932168)

    --- Has therapeutic potential in dry eye disease. (PMID: 20026325)

    --- Reduces LPS-induced NF-kappaB and DA neurotoxicity. (PMID: 18368483)

    --- Protects against infection-driven white matter injury. (PMID: 20403340)

    --- Enhances IL-10 and suppresses p38 MAPK, IL-1beta, and MMP-3 in inflammatory bowel disease. (PMID: 19878610)

    --- Exhibits antiallergic activity via Syk kinase-dependent signaling. (PMID: 18394691)

    --- Reduces cognitive impairment in TBI via reduction of oxidative stress. (PMID: 16364299)

    --- Protects against glutamate excitotoxicity by inhibiting PKC and reducing glutamate-generated ROS as well as by increasing BDNF. (PMID: 17118359, 18420184)

    --- Protects against STZ-inded dementia by reduction of AChE activity and increasing insulin receptor protein level, but does not alter AChE or IR in healthy rats. (PMID: 20026275)

    --- Reverses MPTP-induced DA depletion, at least in part by MAO-B inhibition. (PMID: 18408903)

    --- Inhibits colonic inflammation by inhibition of chemokine expression and neutrophil chemotaxis/chemokinesis. (PMID: 20629184)

    --- Prevented weight loss, impairment of locomotor activity, and anxiety in sleep-deprived mice. Also restored glutathione and catalase. Effects mediated through NO modulation. (PMID: 18586477)

    --- Reversed COX-2 enhancement, PPAR-gamma inhibition, and NF-kappaB translocation induced by amyloid beta in astrocytes. Effects blocked by PPAR-gamma antagonist. (PMID: 20413894)

    --- Inhibits neuroleptic-induced orofacial dyskinesia, apparently by reducion in ROS. (PMID: 18022680)

    --- Stimulates cell proliferation and differentiation of muscle cells, primarily by blocking NF-kappaB. (PMID: 10444409)

    --- Shows anti-allergic properties, with a reduction of histamine release from mast cells. (PMID: 18398870)

    --- Augments endogenous antioxidant systems and preserves myocardial architecture at low (100-200 mg/kg) doses, but medaites ROS induction and myocardial damage at higher (400 mg/kg) concentrations, in a rat model of myocardial necrosis. (PMID: 20029958)

    --- Partially restored daily 5-HT/5-HIIA ratio, with phase shifts in SCN and pineal, in ethanol-withdrawn rats under light/dark conditions. (PMID: 17846884)

    --- Attenuates CFS in murine water immersion stress model of CFS. Curcumin decreased lipid peroxidation, restored GSH, and attenuated immobility in immune-challenged fatigued mice. (PMID: 19159825)

    --- Attenuates amyloid-beta-induced cognitive deficits. (PMID: 11755008)

    --- Protects against ethanol-induced brain damage (PMID: 10548748)

    --- May prevent atherosclerosis by inhibiting lipid peroxidation, stabilizing cellular membranes, inhibitng proliferation of vascular smooth muscle cells, and inhibitng platelet aggregation. (PMID: 16387899)

    --- In a transgenic mouse model of AD, 24 mg/kg p.o. but not 750 mg/kg reduced oxidative damage and amyloid-beta deposition. (PMID: 16387899, 11606625)



    Important Notes



    --- Potent inhibitor of rat CYP1A1/1A2, less potent inhibitor of 2B1/2B2, and weak inhibitor of 2E1. Shows competetive inhibition. (PMID: 8534266, 11346483)

    --- Inhibited CYP1A2 (IC50 40 uM), CYP3A4 (IC50 16.3 uM), CYP2D6 (IC50 50.3 uM), CYP2C9 (IC50 4.3 uM), and CYP2B6 (IC50 24.5 uM). Competetive inhibition toward 1A2, 3A4, and 2B6. Non-competetive toward 2D6 and 2C9. However, the liver typically has low exposure to curcumin. (PMID: 17433521)

    --- Potent inhibitor of glutathione S-transferase. (PMID: 8534266)

    --- Shockingly, acts as an uncoupling agent like DNP. (PMID: 19715674)

    --- Inhibits COX-2, LOX-2, xanthine dehydrogenase/oxidase, iNOS, PKC, EGF-receptor tyrosine kinase, IkappaB kinase, NF-kappaB, c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs, and mTOR while inducing HO-1. (PMID: 17569214)

    --- Ongoing debate between Burgos-Moron et al. (PMID: 19830693, 20198619) and Kurien et al. (PMID: 20198612) regarding the potential of curcumin for DNA damage. Kurien et al. study seems of questionable merit.

    --- Molecular targets include AP-1, SP-1, p53, STAT-3, ATF3, Nrf2, PPAR-gamma, CHOP, HIF1alpha, beta-catenin, and NF-kappaB, as well as enzymes like PKA, PKC, FAK, Src, glutathione S-transferase, DNA topoisomerase-II, telomerase, HO-1, p300 histone acetyltransferase, metaloproteinases, 5-LOX, COX-2, and yet more. (PMID: 20205886)

    --- Age-adjusted incidence of cancers and incidence of AD and PD in India is lower than that in Western countires. Incidence of AD is 4.4-fold lower. (PMID: 16387899,19879924, 20205886)



    Dose and Concentration



    --- Commercial grade curcumin contains 10-20% curcuminoids, desmethoxycurcumin and bisdesmethoxycurcumin, and they are as effective as pure curcumin. It also contains 79-85% curcumin. (PMID: 18274631,19830693)

    --- Animals were given 500mg curcumin/kg body weight. Concentration was maximum in blood at 6 hours and remained elevated at 24 hours. 63.5% was absorbed. Only small proportion is excreted in urine. Bioavailability enhanced when administered with piperine. Intact curcumin was detected (after administration) in brain at 24, 48, and 96 h with a maximum at 48 h. (PMID: 20516541)

    --- Curcumin undergoes extensive metabolic conjugation and reduction in the GI tract and there is more metabolism in human than rat intenstinal tissue. (PMID: 1181540)

    --- In rats treated with curcumin 10 or 20 mg/kg p.o. for 21 days (of restraint stress), plasma concentrations at the end were 55-120 ng/mL. (PMID: 19540859)

    --- Effective in neurological diseases, like AD and depression, with optimum doss of 2.5-25 mg/kg body weight (in mice).

    --- Low concentrations (1 uM for 24 h) protect against cell death, whereas higher concentrations (more than 10 uM) induce cell apoptosis. (PMID: 19540859)

    --- Should not display a "cheese reaction". Given baseline levels of 50 nmol/30 min/mg MAO-A and 236.7 nmom/30 min/mg MAO-B, curcumin p.o. in mice at doses of 1.25 mg/kg, 2.5 mg/kg, 5 mg/kg, and 10 mg/kg reduced these to (44.3, 230.7), (36.4, 210.2), (35.6, 201.6), (34.8,169.2), given as (MAO-A, MAO-/cool.gif' class='bbc_emoticon' alt='B)' />" border="0" alt="cool.gif" />. (PMID: 15987635)

    --- In a transgenic mouse model of AD, 24 mg/kg p.o. but not 750 mg/kg reduced oxidative damage and amyloid-beta deposition. (PMID: 16387899, 11606625)

    --- At 5-20 mg/kg p.o. in rats, reversed escape deficits in footshock avoidance induced by chronic unpredictable mild stress with chroinc treatment. (PMID: 17022948)

    --- At 10-20 mg/kg p.o. in rats, reversed unpredictable chronic stress-induced BDNF decrease accross all hippoampal subfields and reversed 5-HT1A mRNA reduction in CA1 and DG. (PMID: 17617388)

    --- At 5-20 mg/kg p.o. in rats, alleviated stress-induced physiological changes in the adrenal cortex, increase in serum CORT, decrease in hippocampal GR mRNA, and decrease in pCREB/CREB ratio and BDNF in the hippocampus, in line with the effects of imipramine and fluoxetine. (PMID: 17022948)

    --- At 30 mg/kg p.o., reversed chronic unpredictable stress-induced decrease in adenylyl cyclase, cAMP, and CREB activity in hippocampus, cortex, and hypothalamus. (PMID: 19302828)

    --- In a chronic unpredictable stress paradigm, hippocampal and hypothalmus 5-HT1A and 5-HT7 mRNA were upregulated, and 30 mg/kg curcumin p.o. and 7 mg/kg fluoxetine p.o. reversed these effects. They likewise reversed elevated 5-HT1A mRNA in the cortex. Curcumin 15 mg/kg, but not fluoxetine, suppressed stress-induced 5-HT1B mRNA in the hypothalamus. (PMID: 19302828)

    --- Increased 5-HT and NE in frontal cortex and hippocampus and DA in the frontal cortex and striatum. DA was increased to 150% of baseline with 10 mg/kg p.o. in mice. (PMID: 15987635)

    --- Doses as low as 10-20 mg/kg p.o. in rats have been used with good efficacy to reduce neurochemical effects of unpredictable chronic stress. (PMID: 17617388, 17022948)

    --- Plasma concentrations of curcumin in people taking high oral doses are usually in the nanomolar range. (PMID: 19830693, 18559556)

    --- In terms of brain monoamines, piperine (2.5mg/kg i.p. in mice) changed the effects of curcumin 20mg/kg i.p. to resemble those of curcumin 40mg/kg i.p. (PMID: 18766332)

    --- Does not cause short-term toxicity at doses up to 8g/day for 3 months.

    --- Most adult Indians consume 80-200 mg curcumin per day. (PMID: 16387899)



    Caveats



    --- Curcumin delays and partially inhibits meiotic resumption of oocytes and inhibits meiotic and mitotic divisions by disrupting spindle structure and inhibiting CDK1, without inducing DNA damage. Curcumin thereby impairs generative and somatic cell division, with potential side effects of normal cells. (PMID: 20590660)

    --- Inhibits AR expression. (PMID: 20680030, 12239622)

    --- Enhances pathogenicity of salmonella enterica by increasing resistance against antimicrobial agents. (PMID: 20634977)

    --- Protects bacteria S. typhimurium (TA1535/pSK1002), E. coli (K-12), E. coli, B. megaterium, and B. pumilus against DNA inactivation and/or mutagenesis. (PMID: 20634977)

    --- Induces expression of LRRK2 mRNA in rat mesencephalic cells. LRRK2 overexpression is strongly associated with neurodegenerative disorders, suggesting curcumin may have a negative effect. Did not change expression of other PD-risk genes, like alpha-synuclein. Also did not change expression of PD-protective parkin. (PMID: 19879924)

    --- Augments endogenous antioxidant systems and preserves myocardial architecture at low (100-200 mg/kg) doses, but medaites ROS induction and myocardial damage at higher (400 mg/kg) concentrations, in a rat model of myocardial necrosis. (PMID: 20029958, 19830693)

    --- Inhibits phagocytic activity while decreasing ROI and RNI, potentially increasing vulnerability to infectious organisms that are vulnerable to ROS and able to enter cells via phagocytosis. (PMID: 19879991)

    --- Inhibits antigen presentation capacity of dendritic cells, which may be advantageous in autoimmune disease, but disadvantageous otherwise. (PMID: 19879991)

    --- Inhibits IL-12 and IFN production by activated CD4+ T cells. (PMID: 19879991)

    --- Dose-dependently induces chromosomal aberrations in mammalian cell lines at 10 ug/mL concentration. Studies indicate DNA damage and chromosomal abberations both in vitro and in vivo, and at similar concentrations to those with therapeutic benefit. (PMID: 19830693, 17132903, 16537656, 11585363, 15281237, 15790590, 12220536, 9500187, 2209081, 943364)

    --- Rats and mice fed curcumin for 2 years saw increased rates of ulcers, hyperplasia, stomach inflammation, and cancers of the liver and intestine. (PMID: 19830693, 12616304)

    --- Curcumin may promote lung cancer in mice. (PMID: 19830693, 19359593)

    --- Contains 2 alpha,beta-unsatured ketones in chemical structure, which are known to react covalently with exposed thiol groups of cysteine residues, possibly explaining irreversible modification of antioxidant thioredoxin reductase and topoisomerase II-mediated DNA damage, as well as inactivation of tumor-suppressor protein p53. (PMID: 19830693, 15879598, 15008515, 11258951, 15090465)

    --- Iron chelation activity induced iron deficiency anemia in mice fed iron-poor diets. (PMID: 19830693)

    --- At doses of 0.9-3.6 g/day for 1-4 months, increased incidence of nausea and diarrhea as well as serum alkaline phosphatase and lactate dehydrogenase in humans. (PMID: 19830693)

    --- Long-term, low-dose (< 5mg/week) curcumin in mice activates PPARgamma, deactives type 1 response, inhibits iNOS, and interferes with adaptive immunity to exacerbate pathogenesis of Leishmania donovani parasitic disease. When reactive radicals from inflammation play dominant role in pathogen elimination, antioxidant supplements may compromise mocrobial defense. But curcmin may alleviate type 1 disorders. (PMID: 18794851)

    --- Has failed to show efficacy in Alzheimer's disease and cardiovascular diseases. (PMID: 19830693)



    --- Suppresses inflammatory response in collagen-induced arthritis model by altering NF-kappaB and inhibiting PGE-2, COX-2, and MMP. (PMID: 20188213)

    --- Inhibits neuropathic pain by inhibiting NO and TNF-alpha release. (PMID: 16584726)


    No disrepect, but this is a list which pretty much is totally consistent with the broad effects of anti-inflammatories and antioxidants. Not much is specific to curcumin, most of it is the same pattern we have identified as replicable from a broad array of anti-inflammatories and lifestyle influences that work through the same pathways. All this does is confirm the broad picture we already put on plenty of older posts and doesn't tells us that much about really unique about this herb. It is strong dose wise. As its all already down here why do you act like you've just discovered it? People will be telling us their lymes disease could be caused by a virus, and that viral loads have something to do with alzheimers and ADHD next! Then they'll tell me sleep and diet cause the body to become more vulnerable to viruses. Then thell tell us the inflammatory pathways like NF-Kappa trigger the virus to reproduce and hence herbs that are antiinflammatory protect against the virus! Oh wait
    ------



    These ideas are released under a Creative Commons Share and Share alike license

  17. #77
    Senior Member Ex Dubio's Avatar
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    Quote Originally Posted by ATB View Post
    No disrepect, but this is a list which pretty much is totally consistent with the broad effects of anti-inflammatories and antioxidants. Not much is specific to curcumin, most of it is the same pattern we have identified as replicable from a broad array of anti-inflammatories and lifestyle influences that work through the same pathways. All this does is confirm the broad picture we already put on plenty of older posts and doesn't tells us that much about really unique about this herb. It is strong dose wise. As its all already down here why do you act like you've just discovered it? People will be telling us their lymes disease could be caused by a virus, and that viral loads have something to do with alzheimers and ADHD next! Then they'll tell me sleep and diet cause the body to become more vulnerable to viruses. Then thell tell us the inflammatory pathways like NF-Kappa trigger the virus to reproduce and hence herbs that are antiinflammatory protect against the virus! Oh wait


    ...



    Are you honestly accusing me of presenting myself as if I discovered curcumin? ATB, in most posts of your you claim to have discovered half the corpus of modern medicine. Pot...kettle...black...



    But you didn't even read the post, did you? What exactly did I miss about the properties of curcumin that are "really unique"?



    So let me help you out here. Look at the "Pharmacological Actions" section. I made it just for you! So you're telling me that all anti-inflammatory/antioxidant compounds inhibit MAO, agonize M1, inhibit TREk-1 K+, inhibit TRPV1, inhibit AChE, activate PPAR-gamma, activate AMPK, chelate iron, and inhibit mTOR? Bullshit. Do all antioxidants have peculiar, potentially negative, effects like increasing LRRK2 expression? No.



    I did discuss dose-related effects in length, by the way.



    Frankly, this took a huge amount of time to compile; but I did it for my own use. I thought I'd share it, as it might help others. And frankly, it's a lot more useful than two pages of unsubstantiated rambling.

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    I bought some turmeric today for another purpose, but I ended up with 3 pounds of the stuff (cheap + free shipping). I wish it was a stronger extract, but for the priced, it couldn't be beat.



    So what is the desired dose of curcumin? I am taking it with black pepper.



    Thanks!

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    Quote Originally Posted by Ex Dubio View Post
    ...



    Are you honestly accusing me of presenting myself as if I discovered curcumin?


    lol ATB strikes again!
    "Also, can I rig some sort of enema out of household items?" -Tussman

    "I don't have the stamina for a 3-some, and I am a one-pump chump" -Ubiyca

  20. #80
    Senior Member Josh's Avatar
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    Quote Originally Posted by Ex Dubio View Post
    ...



    Are you honestly accusing me of presenting myself as if I discovered curcumin? ATB, in most posts of your you claim to have discovered half the corpus of modern medicine. Pot...kettle...black...



    But you didn't even read the post, did you? What exactly did I miss about the properties of curcumin that are "really unique"?



    So let me help you out here. Look at the "Pharmacological Actions" section. I made it just for you! So you're telling me that all anti-inflammatory/antioxidant compounds inhibit MAO, agonize M1, inhibit TREk-1 K+, inhibit TRPV1, inhibit AChE, activate PPAR-gamma, activate AMPK, chelate iron, and inhibit mTOR? Bullshit. Do all antioxidants have peculiar, potentially negative, effects like increasing LRRK2 expression? No.



    I did discuss dose-related effects in length, by the way.



    Frankly, this took a huge amount of time to compile; but I did it for my own use. I thought I'd share it, as it might help others. And frankly, it's a lot more useful than two pages of unsubstantiated rambling.
    I really like your style of writing Ex Dubio - succinct and specific. Please continue on with your activities as even though I have not been posting much, I do appreciate your works.



    In another post a bit later, I'll try to summarize my conclusions regarding its potential efficacy and risks in a few paragraphs.
    This would be great. The earlier post was quite long, but I appreciate the amount of information that you were covering and the formatting you have used to assist readers in their understanding.



    @ATB - rather than condemning Ex's valuable contributions, why do you not make specific points agreeing/disagreeing with the extant arguments, so as to add value to the debate.



    J
    Stop animal testing on dogs!

    Anti-vivisectionists are a more reliable model.


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