Curcumin

Last Updated: 2023/03/06
Status: In my stack as of 2023/03/05
Dose: 1 gram of Meriva Curcumin twice a day with a fatty meal.
Source: Doctor's Best Curcumin Phytosome with Meriva: $35 for 180 500 mg capsules: https://www.amazon.com/dp/B008YDH4HM?psc=1&smid=ATVPDKIKX0DER&ref_=chk_typ_imgToDp

The case for Curcumin:

1 gram of Meriva Curcumin twice a day with a fatty meal for 12 months improved non-motor symptoms, slowed worsening of motor symptoms, and showed a tendency to decrease misfolded α-syn deposits in skin nerves (1).
• A 2022 study evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients not treated with curcumin (1).
• The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study (1).
• Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed:

• A decrease of COMPASS-31 and NMSS scores (1).

• A slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses (1).

• Note: Simon in The Science of Parkinson's reads this study differently and believes the p-syn load increased for both the treated and untreated, it just increased more in the untreated. I have reached out to the paper's author (1).

• PD patients supplemented with curcumin, despite a stable L-dopa dosage, showed an improvement of nonmotor scales while the worsening of the motor scale was less than expected in the control patients who, by contrast, increased their dosage of L-dopa (1).

• Curcumin chelates iron (4).
• Curcumin inhibits EBV in vitro (8):

• Curcumin Suppresses Proliferation of NPC Cells Positive for EBV (8).
• Curcumin Enhances NPC Cell Apoptosis via Mitochondria- and Death Receptor-Dependent Pathways (8).
• Curcumin Downregulated EBNA1 Expression Levels in NPC Cells Positive for EBV (8).
• Curcumin Reduces Stability and Promotes Proteasomal Degradation of EBNA1 (8).
• Curcumin could inhibit EBV+ HONE1 and HK1-EBV cell proliferation, probably via decreasing EBNA1 expression (8).
• Curcumin Inhibits Replication of EBV in NPC Cells Positive for EBV (8).
• Epstein–Barr nuclear antigen 1 (EBNA1) is a multifunctional, dimeric viral protein associated with Epstein–Barr virus (EBV). EBNA1 is integral to many EBV functions including gene regulation, extrachromosomal replication, and maintenance of the EBV episomal genome through positive and negative regulation of viral promoters.

• Curcumin Reduces Oxidative Stress (9).
• Curcumin Diminishes the Inflammatory Cascade (9).
• Curcumin Has a Protective Effect on the Integrity of the BBB (9).
• Curcumin Improves Mitochondrial Dysfunction and Calcium Overload (9).


Notes:
• Disease duration seems important for the curcumin supplementation, as PD patients with shorter disease duration presented a better clinical outcome (1).
• PD patients supplemented with curcumin, despite a stable L-dopa dosage, showed an improvement of nonmotor scales while the worsening of the motor scale was less than expected in the control patients who, by contrast, increased their dosage of L-dopa (1)
• Curcumin with Broccoli Seed Extract extends Drosphila Melanogaster lifespan more than either supplement alone (5).
• Is able to cross the blood-brain barrier in the form of its active metabolites when formulated in phospholipids (1).
• Is effective in ameliorating/stabilizing motor and nonmotor symptoms in PD (1).
• Shows a tendency to decrease misfolded α-syn deposits in skin nerves (1).

References:

1. The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study 2022 https://academic.oup.com/jnen/article/81/7/545/6585246 Vincenzo Donadio, MD, PhD, IRCCS Istituto delle Scienze Neurologiche, Bologna, Italia, via Altura 3, 40139 Bologna, Italy; E-mail: vincenzo.donadio@unibo.it

There are currently no standardized therapies for Parkinson disease (PD). Curcumin shows anti-amyloidogenic properties in vitro and may be a promising treatment for PD. We evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients to treated with curcumin. The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study. Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed a decrease of COMPASS-31 and NMSS scores, and a slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses. Multiple regression models showed a significant effect of curcumin supplementation in decreasing the worsening of the clinical parameters and p-syn load at after curcumin treatment. These data suggest that curcumin can cross the blood-brain barrier, that it is effective in ameliorating clinical parameters and that it shows a tendency to decrease skin p-syn accumulation in PD patients.

2. An Overview of Parkinson's Disease: Curcumin as a Possible Alternative Treatment 2022 https://www.cureus.com/articles/96465-an-overview-of-parkinsons-disease-curcumin-as-a-possible-alternative-treatment#!/

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain and basal ganglia, followed by dopamine deficiency in the brain. Dopamine plays a crucial role in motor coordination, memory, and cognition; its decrease in PD leads to dyskinesia, cognitive deficits, and depression. In addition, the formation of alpha-synuclein protein aggregates (Lewy bodies) causes further damage to the CNS. Current treatment options include dopamine precursors, inhibitors of dopamine metabolism, upregulation of autophagy, adenosine A2A antagonists, and surgical intervention as a last resort. A challenge arises from a progressive decrease in treatment efficacy as the disease progresses and this necessitates exploration of adjunctive treatments. Epidemiological studies suggest that the prevalence of PD varies between ethnic groups of Caucasians, Asians, and African Americans. Notably, the prevalence of PD is lower in countries of Southeastern Asia including India. The differences in the diet of various ethnic groups may suggest an origin for this difference in the prevalence of PD. One staple ingredient in traditional Asian cuisine is turmeric. Curcuma longa, popularly known as turmeric, is an orange tuberous rhizome that has been used for centuries in traditional Indian cuisine and traditional medicine. Turmeric contains curcumin, a potent antioxidant that scavenges reactive oxygen species and chelates toxic metals. Curcumin has been proposed to be a neuroprotective agent due to its potent antioxidative properties. Though preliminary studies in animal model systems have suggested a protective effect of curcumin on dopaminergic neurons, the direct benefits of curcumin on the progress of PD remains poorly understood. In this review, we explore the promising use of curcumin as an adjunct to conventional PD treatments in order to enhance treatment and improve outcomes.

3. Curcumin Prevents Aggregation in α-Synuclein by Increasing Reconfiguration Rate 2012 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308736/

α-Synuclein is a protein that is intrinsically disordered in vitro and prone to aggregation, particularly at high temperatures. In this work, we examined the ability of curcumin, a compound found in turmeric, to prevent aggregation of the protein. We found strong binding of curcumin to α-synuclein in the hydrophobic non-amyloid-β component region and complete inhibition of oligomers or fibrils. We also found that the reconfiguration rate within the unfolded protein was significantly increased at high temperatures. We conclude that α-synuclein is prone to aggregation because its reconfiguration rate is slow enough to expose hydrophobic residues on the same time scale that bimolecular association occurs. Curcumin rescues the protein from aggregation by increasing the reconfiguration rate into a faster regime.

4. Iron chelation by curcumin suppresses both curcumin-induced autophagy and cell death together with iron overload neoplastic transformation 2019 https://www.nature.com/articles/s41420-019-0234-y

Iron overload, notably caused by hereditary hemochromatosis, is an excess storage of iron in various organs that causes tissue damage and may promote tumorigenesis. To manage that disorder, free iron depletion can be induced by iron chelators like deferoxamine that are of increasing interest also in the cancer field since iron stock could be a potent target for managing tumorigenesis. Curcumin, a well-known active substance extracted from the turmeric rhizome, destabilizes endoplasmic reticulum, and secondarily lysosomes, thereby increasing mitophagy/autophagy and subsequent apoptosis. Recent findings show that cells treated with curcumin also exhibit a decrease in ferritin, which is consistent with its chemical structure and iron chelating activity. Here we investigated how curcumin influences the intracellular effects of iron overload via Fe-nitriloacetic acid or ferric ammonium citrate loading in Huh-7 cells and explored the consequences in terms of antioxidant activity, autophagy, and apoptotic signal transduction. In experiments with T51B and RL-34 epithelial cells, we have found evidence that curcumin-iron complexation abolishes both curcumin-induced autophagy and apoptosis, together with the tumorigenic action of iron overload.

5. Antioxidant Blend of Curcumin and Broccoli Seed Extract Exhibits Protective Effect on Neurodegeneration and Promotes Drosophila Lifespan 2021 https://journals.sagepub.com/doi/full/10.1177/17590914211015033

Antioxidants and related compounds are anti-inflammatory and exhibit great potential in promoting human health. They are also often considered to be important elements in the process of neurodegeneration. Here we describe a antioxidant blend of Curcumin and Broccoli Seed Extract (BSE). Flies treated with the blend exhibit extended lifespan. RNA-seq analysis of samples from adult fly brains reveals a wide array of new genes with differential expression upon treatment with the blend. Interestingly, abolishing expression of some of the identified genes in dopaminergic (DA) neurons does not affect DA neuron number. Taken together, our findings reveal an antioxidant blend that promotes fly longevity and exhibits protective effect over neurodegeneration, demonstrating the importance of antioxidants in health and pathology.

6. Essential turmeric oils enhance anti-inflammatory efficacy of curcumin in dextran sulfate sodium-induced colitis 2017 https://www.nature.com/articles/s41598-017-00812-6

Turmeric has been used as a medicinal herb for thousands of years for treatment of various disorders. Although curcumin is the most studied active constituents of turmeric, accumulating evidence suggests that other components of turmeric have additional anti-inflammatory and anti-tumorigenic properties. Herein, we investigated anti-inflammatory efficacy and associated gene expression alterations of a specific, curcumin preparation containing essential turmeric oils (ETO-curcumin) in comparison to standard curcumin at three specific doses (0, 5, 25 or 50 mg/kg), in an animal model of dextran sodium sulfate (DSS)-induced colitis. The present study showed that both ETO and standard curcumin treatments provided protection against DSS-induced inflammation. However, ETO-curcumin improved disease activity index (DAI) dose-dependently, while the anti-inflammatory efficacy of standard curcumin remained constant, suggesting that ETO-curcumin may provide superior anti-inflammatory efficacy compared to standard curcumin. Gene expression analysis revealed that anti-inflammatory cytokines including IL-10 and IL-11 as well as FOXP3 were upregulated in the colon by ETO-curcumin. Collectively, these findings suggest that the combined treatment of curcumin and essential turmeric oils provides superior protection from DSS-induced colitis than curcumin alone, highlighting the anti-inflammatory potential of turmeric.

7. Protective Effects of Indian Spice Curcumin Against Amyloid Beta in Alzheimer’s Disease 2018 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796761/

The purpose of our article is to assess the current understanding of Indian spice ‘Curcumin’ against amyloid-β (Aβ)-induced toxicity in Alzheimer’s disease (AD) pathogenesis. Natural products, such as ginger, curcumin and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, anti-oxidant, anti-arthritis, pro-healing and boosting memory cognitive functions. In the last decade, several groups have designed and synthesized curcumin and its derivatives and extensively tested using cell and mouse models of AD. Recent research on amyloid-β and curcumin has revealed that curcumin prevents amyloid-β aggregation and crosses the blood brain barrier (BBB), reach brain cells and protect neurons from various toxic insults of aging and amyloid-β in humans. Recent research has also reported that curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD. Further, recent groups have initiated studies on elderly individuals and patients with AD and the outcome of these studies is currently being assessed. This article highlights the beneficial effects of curcumin on AD. This article also critically assesses the current limitations of curcumin’s bioavailability and urgent need for new formulation to increase its brain levels to treat patients with AD.

8. Curcumin Inhibits Proliferation of Epstein–Barr Virus-Associated Human Nasopharyngeal Carcinoma Cells by Inhibiting EBV Nuclear Antigen 1 Expression 2019 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800953/

This investigation aims to study the effect of curcumin on the proliferation, cycle arrest, and apoptosis of Epstein–Barr virus- (EBV-) positive nasopharyngeal carcinoma (NPC) cells. EBV+ NPC cells were subjected to curcumin treatment. The cell viability was evaluated with the CCK-8. Cell cycle and apoptosis were analyzed by flow cytometry analysis. Expression (protein and mRNA) levels were detected with western blotting and quantitative real-time PCR, respectively. Curcumin efficiently reduced the viability of EBV+ NPC cells. Curcumin induced the cycle arrest of the HONE1 and HK1-EBV cells positive for EBV. Moreover, curcumin treatment promoted the NPC cell apoptosis, via the mitochondria- and death receptor-mediated pathways. Furthermore, curcumin decreased the expression of EBNA1 in the HONE1 and HK1-EBV cells and inhibited the transcriptional level of EBNA1 in the HeLa cells. Curcumin induced EBNA1 degradation via the proteasome-ubiquitin pathway. In addition, curcumin inhibited the proliferation of HONE1 and HK1-EBV cells positive for EBV, probably by decreasing the expression level of EBNA1. In both the HONE1 and HK1-EBV cells, curcumin inhibited the EBV latent and lytic replication. Curcumin could reduce the EBNA1 expression and exert antitumor effects against NPC in vitro.

9. Mechanisms Underlying Curcumin-Induced Neuroprotection in Cerebral Ischemia 2022 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9090137/

Ischemic stroke is the leading cause of death and disability worldwide, and restoring the blood flow to ischemic brain tissues is currently the main therapeutic strategy. However, reperfusion after brain ischemia leads to excessive reactive oxygen species production, inflammatory cell recruitment, the release of inflammatory mediators, cell death, mitochondrial dysfunction, endoplasmic reticulum stress, and blood–brain barrier damage; these pathological mechanisms will further aggravate brain tissue injury, ultimately affecting the recovery of neurological functions. It has attracted the attention of researchers to develop drugs with multitarget intervention effects for individuals with cerebral ischemia. A large number of studies have established that curcumin plays a significant neuroprotective role in cerebral ischemia via various mechanisms, including antioxidation, anti-inflammation, anti-apoptosis, protection of the blood–brain barrier, and restoration of mitochondrial function and structure, restoring cerebral circulation, reducing infarct volume, improving brain edema, promoting blood–brain barrier repair, and improving the neurological functions. Therefore, summarizing the results from the latest literature and identifying the potential mechanisms of action of curcumin in cerebral ischemia will serve as a basis and guidance for the clinical applications of curcumin in the future.