Donnie Yance is an internationally known master herbalist and nutritionist. He is the author of the book, "Herbal Medicine, Healing and Cancer" and "Adaptogens in Medical Herbalism"
Icon Sophia within the dome of St. Sophia’s Cathedral in Kyiv, Ukraine.
In the Judeo-Christian tradition, we often refer to “Our Father” when speaking of the cosmic, all-encompassing God. Because God is not really man or woman, referring to God as “he” or “she,” when taken out of context, can be controversial.
But if we were to view God as two sides of the same coin, rather than exclusively one or the other, it might be more helpful. I see God as both masculine and feminine, and the feminine, although more hidden perhaps, is the stronger of the two.
I believe what the world needs now is the Divine Wisdom (Feminine) to be made manifest within all of us.
My heart and prayers are with the Ukrainian people during this tragic time of war. I feel a deep bond with Ukraine stemming from my spiritual and theological roots. Although I was baptized and raised as a Roman Catholic, and taught by Polish Franciscans, I am professed as a Secular Third Order Franciscan in the Eastern Byzantine Ukrainian Catholic Rite.
Below are photos of Holy Protection, the beautiful Ukrainian Franciscan monastery where I lived. It no longer exists, but the sister monastery, Holy Dormition, is still active. I spent a lot of time at that monastery as well. In both monasteries, I was the only non-Ukrainian, and I always felt welcome.
The photo above is of Sts. Volodymyr and Olha Church, in Lviv, Ukraine. It was built since the return of the church in the 1990s when Ukraine was freed from Russia.
The Ukrainian Greek Catholic Church is the largest Eastern Catholic Church in the world. While many such western churches use elaborate sculptural architectural elements, including on the icon screen, the saintly imagery of eastern Byzantine-Rite churches is represented exclusively through two-dimensional, painted icons, not through statues.
The Birth of the Eastern Byzantine Spiritual Tradition
The Eastern Byzantine liturgical, theological and spiritual tradition was born in the first six centuries AD in Constantinople, when it was the capital of the Eastern half of the Roman Empire. The rich traditions evolved from pre-Christian legacies reshaped over a millennium of Christian belief, and were influenced by its relation to the West and the Roman Church for over 400 years.
The Byzantine liturgy is a common inheritance of Eastern Orthodox and Eastern Catholic churches, including the Ukrainian Greek Catholic Church. Its beauty is said to have been the decisive factor that dazzled emissaries of the pagan Kyivan Prince Vladimir, who saw it in Constantinople and “did not know whether they were in heaven or on earth.”[1]
The Divine Liturgy of Saint John Chrysostom, the most frequently celebrated form of the liturgy, provides a good introduction to Byzantine worship in the Ukrainian Greek Catholic Church.
The liturgy invokes God, “Whose power is beyond comparison, Whose glory is beyond comprehension, Whose mercy is beyond measure, and Whose love for humankind is beyond expression.” “You dwell in the holies,” it continues, “with three-fold cries of holy the seraphim acclaim You, the cherubim glorify You, and all the heavenly powers worship You.” Even in (and perhaps through) such transcendent language, believers also see God present in their midst.[2]
Chanting/singing is integral to the liturgy. Almost the whole of it is chanted, even the Gospel reading. Liturgical music is solely dependent on a cappella singing, not on musical instruments.
“Pray for Ukraine Icon”
Icon of Sophia with daughters from a Ukrainian Greek Catholic Church in Ukraine
Praying For Peace
In recent days within the Ukraine, archbishop Sviatoslav Shevchuk of Kyiv-Halych, head of the Eastern-rite Ukrainian Catholic Church, traveled from Kyiv to meet with Cardinal Krajewski and with Archbishop Mieczyslaw Mokrzycki, head of the Latin-rite Archdiocese of Lviv. The three joined representatives of other Christian churches and other religions at the Latin-rite cathedral to pray for peace.
Archbishop Shevchuk turned to God, praying: “Before your eyes today we present the sorrow and pain of Ukraine. Mountains of corpses, rivers of blood and seas of tears. We pray for all those who gave up their lives for the homeland, for our army, for the sons and daughters of Ukraine, who shield lives with their own bodies in the face of the enemy.”
“We pray for all those innocently killed, peaceful people of Ukraine: women, children, the elderly. We pray for the victims of Mariupol who are being buried in massive common graves without Christian burial and honor,” he continued. “Receive our prayers for their eternal repose.”
Ukrainian citizens in the town of Bakhmach, some 175 kilometers (109 miles) northeast of the capital of Kyiv, attempted to block Russian tanks advancing, according to video footage that circulated on social media on Saturday.
Residents of Bakhmach, Ukraine, attempt to stop Russian tanks from advancing toward the capital Kyiv, February, 26, 2022. (Screengrab/Twitter)
The “National Spiritual Anthem” of Ukraine (МОЛИТВА ЗА УКРАЇНУ). This hymn is familiar to most Ukrainians. The English lyrics are as follows:
Lord, oh the Great and Almighty, Protect our beloved Ukraine, Bless her with freedom and light Of your holy rays.
With learning and knowledge enlighten Us, your children small, In love pure and everlasting Let us, oh Lord, grow.
We pray, oh Lord Almighty, Protect our beloved Ukraine, Grant our people and country All your kindness and grace.
Bless us with freedom, bless us with wisdom, Guide into kind world, Bless us, oh Lord, with good fortune Forever and evermore.
Take time to listen to this beautiful, heartfelt prayer. It brings tears to my eyes:
The most beautiful churches in Kyiv – WHAT IS UKRAINE
Fifty percent of all drugs, including cancer drugs marketed today, use the cytochrome P450 enzyme pathway for metabolism[1],[2] and frequently cause interactions. In brief, the cytochrome P4503A (CYP3A) subfamily is largely found in hepatocytes, with some presence in the intestine. Together with the transport protein P-glycoprotein (PGP) present in the small intestine, these 2 systems regulate metabolism of drugs and nutrients. Many foods, food components, and botanical supplements interact with the CYP3A and PGP metabolism, but even more importantly, an individual’s genome plays a significant role in how well one metabolizes and detoxifies various drugs including Aromatase and mTOR inhibitors. The effects of herbs on CYP3A and PGP is dose sensitive, meaning that often the dose would need to be very high in order to really impact these pathways. Another important factor is that much of the published research is either in vitro; animal in vivo, done with isolates (not whole herbs), and/or based on high dosages of these compounds. So, every referenced paper needs to be reviewed and analyzed for accuracy and relativity to how botanicals might impact both the effectiveness or toxicity of these and other drugs. The other factor is that to base interaction solely on P4503A and PGP is wrong. The ultimate question is still not answered, which is does this herbal combination either cause this drug to be less effective or does it increase the toxicity? In general, due to these nuances, evaluating the potential for negative drug-drug, nutrient-drug, or botanical-drug interactions metabolized through this pathway can be difficult and often lead to incorrect assumptions.
Many chemotherapeutic drugs have been used for the treatment of cancer, including doxorubicin, irinotecan, 5-fluorouracil, cisplatin, and paclitaxel. However, the effectiveness of chemotherapy is limited in cancer therapy due to drug resistance, therapeutic selectivity, and undesirable side effects.
Chemosensitization is one valuable strategy to overcome chemoresistance phenomena. Chemosensitization is based on the use of one drug to enhance the activity of another by influencing one or more mechanisms of resistance. The combination of therapies with natural compounds such as curcumin is likely to increase the effectiveness of drug treatment as well as reduce the incidence of adverse outcomes.
Curcumin, a polyphenolic isolated from Curcuma longa, belongs to the rhizome of Zingiberaceae plants.
Both in vitro and in vivo studies show that curcumin exerts many pharmacological activities with less toxic effects. Chemosensitization has been observed in cancers of the breast, colon, pancreas, gastric, liver, blood, lung, prostate, bladder, cervix, ovary, head and neck, and brain and in multiple myeloma, leukemia, and lymphoma. Similar studies have also shown that curcumin can sensitize a variety of tumors to gamma radiation including glioma, neuroblastoma, cervical carcinoma, epidermal carcinoma, prostate cancer, and colon cancer. The way in which curcumin acts as a chemosensitizer and radiosensitizer has been studied extensively. For example, it downregulates various growth regulatory pathways and specific genetic targets including genes for NF-κB, STAT3, COX2, Akt, antiapoptotic proteins, growth factor receptors, and multidrug-resistance proteins. Although it acts as a chemosensitizer and radiosensitizer for tumors in some cases, curcumin has also been shown to protect healthy organs such as the liver, kidney, oral mucosa, and heart from chemotherapy and radiotherapy-induced toxicity.[3]
The Bioavailability of Curcumin: Separating Truth from Fiction
Curcumin and other curcuminoids from Curcuma longa (turmeric) are important bioactive compounds exhibiting various pharmacological activities. Turmeric is widely consumed as part of the spice mix curry and as a dietary supplement. It has a long history of therapeutic application in traditional Asian medicine. The active components of turmeric, collectively known as curcuminoids, are among the most promising natural compounds studied across the globe today.
Clinical studies support the active role of curcuminoids in the management of chronic health conditions. Several pioneering studies have been conducted by major universities, research institutes and hospitals on Curcumin C3 Complex®, which have aided the understanding of the metabolic effects of curcumin.
Curcumin is a natural product with multiple biological activities and numerous potential therapeutic applications. However, the poor systemic bioavailability of the product fails to explain the potent pharmacological effects and hinders its clinical application.
The biological effects of curcumin in cellular and animal models are surprising considering its chemical and metabolic instability. Multiple studies have shown that, even with high doses of curcumin, the levels of curcumin in serum and tissues as well as its in vivo metabolites are extremely low after a short period of time.
With a lack of consensus on curcumin bioavailability and with various formulations making a variety of claims on the bioavailability (X times or XX times more than nearest competitor), consumers are understandably confused.
The reality is that after ingestion, little if any curcumin is present unchanged in systemic circulation.Furthermore, curcumin undergoes rapid non-enzymatic degradation in cell culture medium and possibly in vivo as well. Chemical transformation by human gut microbiota does not mean a loss in activity, but is actually a necessity for the therapeutic action of curcumin. Current thinking is that the molecular mechanisms of degradation of curcumin is necessary for interpreting in vitro and in vivo studies.
Compared to the parent compound curcumin, the degradation products mixture possessed higher O2.–-scavenging activity and stronger inhibition against fAβ formation. The docking simulations revealed that the bioactive degradation products make an important contribution to the experimentally observed enzymatic inhibition activities of curcumin.
Curcumin has been shown to possess low stability in aqueous solutions at physiological pH and degrades readily.. In phosphate buffer at pH 7.4, about 90% of curcumin degraded within 30 min and the degradation products have been identified as trans-6-(4′-hydroxy-3′-methoxyphenyl)-2,4-dioxo-5-hexenal, ferulic aldehyde, ferulic acid, feruloyl methane, vanillin, vanillic acid, and other dimerization end-products.
Selected degradation products mentioned above were the major human metabolites after curcumin consumption, and their levels were much higher than those of its metabolic compounds.
Upon ingestion, curcumin forms several active metabolites undergoing phase I metabolism such as dihydrocurcumin, tetrahydrocurcumin, hexahydrocurcumin and octahydrocurcumin.
In course of its metabolism, it also forms degradation compounds such as ferulic acid and bicyclopentadione. While these phase I metabolites have shown to have beneficial biological activity, compounds such as curcumin glucuronides and sulfates formed after phase II metabolism have shown to be ineffective in independent studies.
Given that curcumin is readily degraded under physiological condition, recent findings strongly suggested that the degradation products should make important contribution to the diverse biological activities of curcumin.[4],[5],[6],[7]
Oral curcumin also improved cachexia and general health in colorectal cancer patients.[8] In a phase II trial involving 21 patients with advanced pancreatic cancer, curcumin demonstrated bioactivity by downregulating nuclear factor-κB and cyclooxygenase-2. Despite limited absorption, antitumor response was seen in two patients.[9]
Curcumin Combined with Various Chemotherapeutic Agents
Combined with 5-FU
Research suggests that the combination of 5-FU and curcumin may overcome drug-resistance induced by 5-FU. Pre-treatment with curcumin (5 µM) enhanced the chemosensitization of 5-FU (0.1 µM) and reversed the multidrug resistance in resistant mismatch repair (MMR)-deficient human colon cancer cells compared to 5-FU alone.[10]
The combination of curcumin (10 μM) and 5-FU (0.1 mM)/oxaliplatin (5 μM) enhanced the synergistic antitumor activity in gastric cancer (BGC-823) cell lines compared to curcumin or 5-FU/oxaliplatin alone by downregulating the Bcl-2 mRNA and protein expression and activating the Bax and caspases-3, 8, and 9 expressions. This study further demonstrated that the combination of curcumin (10 mg/kg) and 5-FU (33 mg/kg)/oxaliplatin (10 mg/kg) shows potent growth inhibition of BGC-823 xenograft tumors compared to folinic acid, 5-FU, oxaliplatin (FOLFOX) or curcumin alone.[11]
A combination of curcumin (50 mg/kg/day for 40 days) and 5-FU (20 mg/kg once every 2 days for 40 days) inhibits cell proliferation against 5-FU resistant cells via suppression of epithelial-to-mesenchymal transition (EMT) compared to 5FU alone.[12]
In the context of breast cancer, a combination of curcumin (10 µM) and 5-FU (10 µM) significantly inhibited cell viability and enhanced apoptosis compared to 5-FU alone in vitro.[13]
In addition to the effects mentioned above, research indicates that combining 5-FU (50 µmol/L) and curcumin (25 µmol/L) can enhance the cytotoxicity against human gastric cancer (AGS) cells compared to 5-FU or curcumin alone.
In a further study focused on inflammation outcomes, this study found that the protein expression of COX-2 and NF-κB in human gastric cancer (MKN45) cells were diminished after co-treatment with 5-FU (50 µmol/L) and curcumin (25 µmol/L). This finding implies that curcumin sensitizes gastric cancer cells to 5-FU by modulating inflammatory molecules. The anti-gastric cancer activity is shown not only in in vitro study, but data from an animal study further demonstrated that curcumin enhanced the anticancer activity of 5-FU (52 mg/kg 5-FU + curcumin 74 mg/kg, every 3 days for 6 times in total) compared to 5-FU or curcumin alone, and without increasing the toxicity in nude mice bearing MKN45 tumor xenografts.[14]
Combined with Doxorubicin
Doxorubicin, one of the active single-agent drugs, is widely used for the treatment of cancers, including leukemia, lung, brain, prostate, ovarian, and breast. However, the clinical use of doxorubicin often led to critical cardiotoxicity and developed multidrug resistance. Substantial evidence showed that curcumin (4 mg/kg every 2 days for a total of 7 injections) exhibits a better treatment efficacy of doxorubicin (0.4 mg/kg) in cancer due to the efflux inhibitory effect of curcumin.[15],[16],[17],[18]
A study conducted by Guorgui et al.[19] has shown that combination of curcumin (5 µM) and doxorubicin (0.4 mg/mL) demonstrated a stronger additive effect by reducing the proliferation of Hodgkin lymphoma (L-540) cells by 79%. The pharmacokinetic study also revealed that curcumin (5 mg/kg) could enhance the absorption of doxorubicin (5 mg/kg) and decrease drug efflux in vivo, suggesting that curcumin downregulates the intracellular levels of ATP-binding cassette (ABC) drug transporters.[20]
While DOX alone does not decrease tumor weight, the combination of DOX and curcumin has been shown to significantly reduce tumor weight to 56.5% (p<0.05) to that of the control group. In combination, curcumin enhanced apoptosis by DOX and decreased cell viability. The curcumin-DOX combination also suppressed activation of caspase-3, -8, and -9 compared to DOX alone. It appears that curcumin increases DOX-induced antitumor activity by suppressing the main caspase pathway and activating the main caspase independent pathway. The combination of curcumin and DOX suppressed the reduction of glutathione peroxidase activity and increased lipid peroxide levels in the heart. Therefore, it is expected that curcumin may reduce the adverse reactions associated with DOX. According to researchers, results suggest that curcumin can be used as a modulator to enhance the therapeutic index of cancer patients and improve their QOL.[21]
Combined with Platin Agents
Cisplatin-based combination therapy has emerged as a standard therapy for metastatic and advanced bladder cancer,[22] demonstrating 15–20% improved survival and 50–70% response rate. However, nearly 30% of patients do not respond to initial chemotherapy and show recurrence within 1 year.[23] Cisplatin is an inorganic platinum agent which can induce DNA-protein and interstrand and intrastrand DNA crosslinks.[24]
While this crosslink can induce apoptosis and inhibit cell proliferation,[25] the efficacy of cisplatin is limited by the development of cell resistance. Co-treatment with curcumin (10 µM) and cisplatin (10 µM) has shown a potent synergistic effect by activating caspase-3 and upregulating phospho-mitogen-activated protein kinase (p-MEK) and phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) signaling in bladder cancer cell lines (253J-Bv and T24) compared to curcumin or cisplatin alone.[26] In addition to the effects observed on bladder cancer, the combination of curcumin and cisplatin was shown to upregulate the expression of miR-186 via modulation of Twist1 in ovarian cancer compared to cisplatin alone.[27]
Synergism of Curcumin and Epigallocatechin-3-gallate
Drug resistance remains an ongoing challenge in ovarian cancer chemotherapy. Research has investigated the synergism in activity from the sequenced combinations of cisplatin (Cis) with curcumin (Cur) and epigallocatechin-3-gallate (EGCG) in ovarian cancer cell lines. The drugs were added in binary combinations: Cis combined with Cur, and Cis combined with EGCG to the human ovarian A2780 and A2780(cisR) cancer cell lines, using five different sequences of administration: 0/0 h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. Addition of Cis 4 h before Cur and EGCG (0/4 h combination) produced the most synergistic outcomes in both the A2780 and A2780(cisR) cell lines. The cellular accumulations of platinum and platinum-DNA binding resulting from the 0/4 h combinations were greater as compared to the values using Cis alone, thus providing an explanation for the synergistic action. When sequenced combinations of Cis with Cur and with EGCG are applied to human ovarian A2780 and A2780(cisR) cancer cell lines, lower concentrations and shorter time gap between the two additions seem to produce a higher cytotoxic effect.[28]
Curcumin, EGCG (Green tea extract) and Resveratrol Immune Enhancing Anti-tumor
Curcumin, Resveratrol, EGCG and Beta glucan rich mushroom extract have shown promising immune-modulating effects, such as inhibiting myeloid-derived suppressor cells and enhancing natural killer and cytolytic T cells, in tumor-bearing animal models.
Many other studies involving either genetic models or xenograft models of other types of cancer have demonstrated that curcumin can reverse the tumor-favoring microenvironment, leading to further investigations of curcumin combined with standard cancer therapies. One study combined the anti-PD-L1 antibodies with bisdemethoxycurcumin (BDMC), a natural dimethoxy derivative of curcumin, in C57BL/6 mice with metastasized bladder cancer (MB49 cells).
They observed that BDMC alone increased levels of tumor-infiltrating CD8+ T cells, IFN-γ secretion in the blood, and decreased the number of tumor-infiltrating MDSCs.
Importantly, the combination of anti-PD-L1 antibodies with curcumin further enhanced the secretion of IFN-γ, granzyme B, and perforin from CD8+ T cells.[29]
Furthermore, curcumin has been combined with vaccines against tumor development. For instance, one group applied two vaccination strategies to BALB/c mice bearing triple-negative breast tumors (4T1 cells). One strategy gave the mice curcumin and all the vaccinations after tumors had developed. The other treated the mice with curcumin before they were inoculated with tumor cells and then vaccinated the animals after tumors developed. Interestingly, the second strategy was more effective against metastasis than the first, as it decreased the production of pro-inflammatory cancer promoting cytokines (IL-6), and increased levels of anti-tumor cytokines (IL-12 and IFN-γ).[30]
A cocktail of Turmeric- curcumin, Green tea epicatechin gallate and resveratrol—increased levels of tumor-infiltrating NK cells and CD8+ cytolytic T cells in C57BL/6 mice bearing HPV+ mouse lung cancer (TC-1 cells).
The combination formula repolarized tumor promoting M2-like TAMs to tumor fighting M1-like TAMs in the tumors.[31]
Combined with Taxanes
Docetaxel (30 or 75 mg) has been clinically approved and widely used for the treatment of metastatic castration-resistant prostate cancer.[32] However, prolonged treatment with docetaxel can cause severe toxicity in patients. A study found that the combined treatment of docetaxel (10 nM) and curcumin (20 µM) for 48 h significantly inhibited proliferation and induced apoptosis in prostate cancer (PC-3) (DU145 and PC3) cells compared to curcumin and docetaxel alone. The data further demonstrated that curcumin enhances the efficacy of docetaxel in PC-3 cells via modulation of COX-2, p53, NF-κB, phospho-Akt, PI3K, and receptor tyrosine kinase (RTK).[33] This finding implies that combining curcumin with conventional chemotherapy may act as an effective treatment regimen for patients with prostate cancer to reduce cytotoxicity and overcome drug-resistance induced by docetaxel.
Curcumin is a taxane sensitizer for tumors and chemoprotector for normal organs, including in cases of lung cancer.[34]
Curcumin induces apoptosis and inhibits the growth of orthotopic human non-small cell lung cancer xenografts. A research study evaluated the effect of curcumin on the expression of nuclear factor κB-related proteins in vitro and in vivo and on growth and metastasis in an intralung tumor mouse model.
H1975 NSCLC cells were treated with curcumin (0-50μM) alone, or combined with gemcitabine or cisplatin. The effects of curcumin were evaluated in cell cultures and in vivo, using ectopic and orthotopic lung tumor mouse models. Western blot analysis showed that the expressions of IkB, nuclear p65, cyclooxygenase 2 (COX-2) and p-ERK1/2 were down-regulated by curcumin in vitro. Curcumin potentiated the gemcitabine- or cisplatin-mediated antitumor effects. Curcumin reduced COX-2 expression in subcutaneous tumors in vivo and caused a 36% decrease in weight of intralung tumors (P=.048) accompanied by a significant survival rate increase (hazard ratio=2.728, P=.036). Curcumin inhibition of COX-2, p65 expression and ERK1/2 activity in NSCLC cells was associated with decreased survival and increased induction of apoptosis. Curcumin significantly reduced tumor growth of orthotopic human NSCLC xenografts and increased survival of treated athymic mice. Researchers note that to evaluate the role of curcumin in chemoprevention and treatment of NSCLC, further clinical trials are required.[36]
Curcumin Induces PTEN and Improves the Cytotoxicty of Gemzar Against Pancreatic Cancer
Curcumin induces cancer cell growth arrest and apoptosis in vitro, but its poor bioavailability in vivo limits its antitumor efficacy. Researchers noted that in previous evaluations of the bioavailability of novel analogues of curcumin compared with curcumin, they found that the analogue CDF exhibited greater systemic and pancreatic tissue bioavailability.
In a study reported in Cancer Research, scientists evaluated the effects of CDF or curcumin alone or in combination with gemcitabine on cell viability and apoptosis in gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer (PC) cell lines. Mechanistic investigations revealed a significant reduction in cell viability in CDF-treated cells compared with curcumin-treated cells, which were also associated with the induction of apoptosis, and these results were consistent with the downregulation of Akt, cyclooxygenase-2, prostaglandin E(2), vascular endothelial growth factor, and NF-kappaB DNA binding activity.
The researchers documented attenuated expression of miR-200 and increased expression of miR-21 (a signature of tumor aggressiveness) in gemcitabine-resistant cells relative to gemcitabine-sensitive cells. Interestingly, CDF treatment upregulated miR-200 expression and downregulated the expression of miR-21, and the downregulation of miR-21 resulted in the induction of PTEN. These results prompt further interest in CDF as a drug modality to improve treatment outcome of patients diagnosed with PC as a result of its greater bioavailability in pancreatic tissue.[37]
Mechanisms of action of combination curcumin and chemotherapy drugs in vitro and in vivo. Co-treatment with curcumin and chemotherapy drugs such as docetaxel, metformin, 5-fluorouracil, doxorubicin, cisplatin, and celecoxib enhance the synergistic effect via modulating several signaling pathways and thus inhibit cancers such as prostate, hepatocellular, gastric, Hodgkin lymphoma, bladder, and colorectal. Akt: protein kinase B; COX-2: cyclooxygenase-2; EGFR: epidermal growth factor receptor; MMP2/9: matrix metalloproteinase-2/9; mTOR: mammalian target of rapamycin; NF-κB: nuclear factor kappa B; p-ERK1/2: phospho-extracellular signal-regulated kinase 1/2; PI3K: phosphoinositide 3-kinase; p-MEK: phospho-mitogen-activated protein kinase; STAT3: signal transducer and activator of transcription 3; VEGF: vascular endothelial growth factor; VEGFR2: vascular endothelial growth factor receptor 2.
Paclitaxel (PTX) is a key member of the taxane family with potential anti-tumor activity against different cancers. Notably, PTX has demonstrated excellent proficiency in elimination of cancer in clinical trials. This chemotherapeutic agent is isolated from Taxus brevifolia and is a tricyclic diterpenoid. However, resistance of cancer cells into PTX chemotherapy has endangered its efficacy. In addition, administration of PTX is associated with a number of side effects such as neurotoxicity, hepatotoxicity, and cardiotoxicity, demanding novel strategies in obviating PTX issues.
Curcumin is a pharmacological compound with diverse therapeutic effects including anti-tumor, antioxidant, anti-inflammatory, and anti-diabetic properties. Curcumin appears to enhance the anti-tumor activity of PTX against different cancers. Additionally, curcumin administration reduces the adverse effects of PTX due to its excellent pharmacological activities.[40]
Combined with Metformin
Data from an in vitro study showed that combining metformin (10 mM) and curcumin (5 and 10 µM) can induce apoptosis and inhibit metastasis and invasion in HepG2 and PLC/PRF/5 cells. The anticancer effects could be attributed to the vascular endothelial growth factor (VEGF), MMP2/9, and vascular endothelial growth factor receptor 2 (VEGFR-2) inhibition, PTEN and p53 activation, and epidermal growth factor receptor (EGFR)/STAT3 and NF-κB/mTOR/Akt/PI3K suppression. Data from an in vivo study further showed that co-treatment with metformin and curcumin significantly suppressed hepatocellular carcinoma compared to curcumin (60 mg/kg) and metformin (150 mg/kg) alone in a xenograft mouse model.[41]
Combined with Celecoxib and COX-2 inhibitor
Celecoxib is another selective inhibitor of COX-2, an enzyme induced by different stimuli including inflammation.[42] Celecoxib (75 µM for 16 h) has shown an ability to induce apoptosis and suppress tumor angiogenesis in several types of cancer.[43] However, the long-term use of Celecoxib leads to an adverse outcome such as cardiovascular toxicity.[44] The combination of curcumin and Celecoxib was shown to reduce cancer cell growth in vitro compared to Celecoxib alone. A study reported by Lev-Ari et al. revealed that curcumin (10–15 µmol/L) and physiological dosage of Celecoxib (5 µmol/L) exhibited a synergistic inhibitory effect against human colorectal cancer (HT-29) cells. The study showed that the combination of curcumin and Celecoxib induces apoptosis in HT-29 cells via downregulation of COX-2 expression, suggesting that curcumin synergistically augments the growth inhibitory effects of Celecoxib in human colon cancer cell lines in vitro.[45]
Another anti-cancer property of curcumin seems to be overcoming multidrug resistance.[46] For example, it inhibits P-glycoprotein expression in mouse leukemia L1210/Adr cell lines. Cells treated with a combination of PI3K inhibitor and curcumin displayed lower P-glycoprotein expression in comparison to cells treated only with PI3K inhibitor. It was suggested that curcumin may act by inhibition of the PI3K/Akt/ NF-κB pathway.[47]
Curcumin was found to be a safe and non-toxic dietary supplement. Its efficacy of was studied during clinical trials.[48],[49]
In the mouse model, a high curcumin supplementation (100 mg/kg) was able to improve glucose and insulin intolerance through activating the AMPK pathway, showing the potential involvement of curcumin in metabolism.[50] Modulation of AMPK (AMP-activated protein kinase) improves glucose/insulin efficiency and adds the cancer suppressing effects of curcumin. AMPK acts as a cellular energy sensor, and curcumin selectively can enhance normal cell AMPK signaling, while suppressing it within the cancer cell. [51],[52]
Curcumin in the Modulation of Aging
Overview of the impact of curcumin on ageing and age-related diseases (ARD) at the organismal and cellular level. On the organismal level, curcumin mimics caloric restriction (CR) and improves the effectiveness of physical activity (which mimics CR).[53]
In Conclusion
Natural compounds, including curcumin, resveratrol, EGCG, and β-glucan have shown synergistic promising immune-modulating, anti-tumor, and chemo-potentiating effects.
The results of these clinical studies are conclusive, and these studies have established a good foundation for further research focusing on implementing curcumin along with other botanical compounds in clinical oncology. It’s important to note, however, that I never use it as a soloist! I always use a formula that combines curcumin with EGCG, resveratrol, grape seed extract, quercetin, and other botanical extracts. This provides a harmonious approach that best supports healing.
[2] Zhou SF, Xue CC, Yu XQ, Li C, Wang G. Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther Drug Monit. 2007 Dec;29(6):687-710. doi: 10.1097/FTD.0b013e31815c16f5. PMID: 18043468.
[3] Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer. 2010;62(7):919-30. doi: 10.1080/01635581.2010.509835. PMID: 20924967.
[4] Majeed M. The Age of Biotransformation, 2015; Personal communication. Ganjali S, Sahebkar A, Mahdipour E, Jamialahmadi K, Torabi S, Akhlaghi S, Ferns G, Parizadeh SM, Ghayour-Mobarhan M. The Scientific World Journal 2014; doi 10.1155/2014/898361
[5]Liang Shen, Cui-Cui Liu, Chun-Yan An, Hong-Fang Ji, How does curcumin work with poor bioavailability? Clues from experimental and theoretical studies, Scientific Reportsvolume 6, Article number: 20872 (2016), Published: 18 February 2016
Many plant molecules, such as polyphenols, interact with and modulate key regulators of mammalian physiology in ways that are beneficial to health. The more we understand about this interaction, the more effectively we can target both the prevention and treatment of disease.
Polyphenol compounds, when ingested, interact with receptors and enzymes within the consumer. The fact that stress-induced plant compounds tend to upregulate pathways that provide stress resistance in humans and animals suggests that plant consumers may have mechanisms to perceive these chemical cues and react to them in ways that are beneficial. The term xenohormesis is used to explain this phenomenon (from xenos, the Greek word for stranger, and hormesis, the term for health benefits provided by mild biological stress, such as cellular damage or a lack of nutrition).[1]
“When one tries to rise above nature, one is liable to fall below it.” – Sherlock Holmes
While the Centers for Disease Control (CDC) maintains that vaccine immunity is superior to natural immunity, evidence continues to mount suggesting that natural immunity is superior and long-lasting. In my coverage of Covid-19 over the past two years, I’ve documented several studies supporting the fact that natural immunity is superior to vaccination, including studies conducted while the Delta variant was dominant. One study, published January 20th, 2022, was backed by the CDC.[1]
According to a study published in JAMA in early February 2022,[2] antibody protection against COVID-19 among the recovered was detected by researchers at 20 months post-infection, adding to the body of evidence that such protection, known as natural immunity, is long-lasting.
Natural Immunity is Strong and Durable
Researchers found antibodies against the SARS-CoV-2 spike protein receptor-binding domain in 99 percent of study participants who tested positive for COVID-19, with some having had the illness 20 months prior.
“The major takeaway is that natural immunity … is strong and durable,” says Dr. Dorry Segev, the Director of the Epidemiology Research Group in Organ Transplantation at Johns Hopkins University.[3]
Natural immunity occurs from an orchestrated immune response which includes not only T and B cells, but-interferons (a family of cytokins with anti-viral properties) and other first-line defenders, while vaccine induced immunity shares some of the same response, is less robust, and less orchestrated. A central point is the important distinction between the impact of vaccination versus natural infection on type I interferon (IFN). While vaccination actively suppresses its production, natural infection promotes type I IFN production very early in the disease cycle.[4],[5]
This is a very important distinction because the argument stating vaccine immunity is better is solely based on the fact that mRNA vaccinations produce more neutralizing receptor binding domain antibodies than natural immunity,[6] which involves many more immunologically active components.
The COVID-19 mRNA vaccines’ ability to produce adverse reactions in individuals suffering from immune-mediated diseases, with therefore an inherent pre-existing dysregulation of the immune response, has not been investigated. In such cases, mRNA may bind pattern recognition receptors in endosomes or cytosol and cause immune chaos, as if the orchestra lost the music score. This leads to the activation of several pro-inflammatory cascades, including the assembly of inflammasome platforms, the type I IFN response and the nuclear translocation of the transcription factor nuclear factor (NF)-kB.[7]
Importantly, the up-regulation of these immunological pathways is widely considered to be at the basis of several immune-mediated diseases, especially in genetically predisposed subjects who have an impaired clearance of nucleic acids.[8]
A recent publication (January 21, 2022) in the Journal Authorea,[9] goes as far as to state the following concerns with regard to the mRNA vaccines: “the genetic modifications introduced by the vaccine are likely the source of these differential responses. In this paper, we present the evidence that vaccination, unlike natural infection, induces a profound impairment in type I interferon signaling, which has diverse adverse consequences to human health. We explain the mechanism by which immune cells release into the circulation, large quantities of exosomes containing spike protein along with critical microRNAs that induce a signaling response in recipient cells at distant sites. We also identify potential profound disturbances in regulatory control of protein synthesis and cancer surveillance. These disturbances are shown to have a potentially direct causal link to neurodegenerative disease, myocarditis, immune thrombocytopenia, Bell’s palsy, liver disease, impaired adaptive immunity increased tumorigenesis, and DNA damage.”
Long before COVID-19, it has been well known within the scientific community that a person develops natural immunity after recovering from an infection. The protection afforded by natural immunity is what all vaccines strive to achieve. Some vaccines do this better than others, but vaccines rarely surpass natural immunity.
The Pursuit of Truth
On Nov. 28, 2021, Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID) and the chief medical adviser to the President of the United States, said on CBS’s Face the Nation: “It’s easy to criticize [me], but they are really criticizing science, because I represent science.”
Once the SARS-CoV-2 outbreak had begun, virologists quickly reached the conclusion that the pandemic was almost certainly of natural origin. Quickly the media called out such a notice has a radical conspiracy theory and the possibility of a lab leak was actively censored by Facebook and other social media platforms. Nonetheless, significant evidence has continued to build in support of the “lab leak hypothesis,”[10] so much so I invite you to read this paper entitled, “Thunder out of China” by Yuri Deigin, in Interference, Vol. 6, No. 4, February 2022. Be prepared to be enlightened. There are 152 citations in the paper, and they all support what the author Yuri speaks to.
It seems as though our government and most of the media censors anything other than what is considered to be “science.” I believe in the value of science, but I also believe that we should have open debate instead of being told what is the “truth.”
The Merriam-Webster Dictionary defines science as “knowledge about or study of the natural world based on facts learned through experiments and observation.” So, science is human knowledge of facts. It has nothing to do with human intention or politics. Consider the fact that the Chinese Communist Party (CCP) represents science in China. The CCP’s science is not to be criticized or questioned, but to be followed. If you criticize the Party, you are criticizing the representative of science. Now suddenly, in the United States, it seems that anyone who challenges the validity of the mRNA vaccines is labeled “anti-science” which has given rise to those that are so extreme in the opposite direction that even among the medical community they are now referred to as “anti-anti-science”.
Science is simply about facts and truth. The interpretation of facts is often debated to reach well-thought-out conclusions. Research findings must go through a peer-review process before being recognized as scientific. According to Joe Wang, PhD: “It seemed that the SARS-CoV-2 origin narrative had been decided upon—even when the existing facts did not support the narrative. The scientists took the existing facts and forced them to fit the preferred narrative, and also forced the general public to accept it, while silencing all other opinions and essentially banning scientific debate on the issue.”[11]
“It is a capital mistake to theorize before one has data. Insensibly one begins to twist facts to suit theories, instead of theories to suit facts.” ~Sherlock Holmes
Vitamin D Deficiency Linked to Severity, Deaths among COVID-19 Patients
If there is one thing I know for sure, it is that science is confirming over and over again that normalizing vitamin D levels consistently is associated with significantly better outcomes in COVID-19 patients. A new study has found that vitamin D deficiency is associated with severe cases of COVID-19 as well as mortality. The research has been published in the ‘PLOS ONE Journal’.
Existing literature suggests a potential protective effect of supplemental vitamin D in preventing and treating COVID-19 disease.[12] A published meta-analysis of 43 observational studies analyzing data obtained from 612,601 patients showed that vitamin D deficiency (defined as 25(OH)D of 30 ng/mL (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.19 to 1.34; p < 0.01). One meta-analysis of three randomized controlled trials (RCTs) and two Quasi-experimental analyzing data obtained from 467 patients has raised doubt as to whether low vitamin D is associated with an increased risk of acquiring COVID-19.[13] A more recent placebo-controlled, double-blind RCT tested the effect of calcifediol 25 (OH)D3 treatment in 106 COVID-19 Iranian patients and found that an oral calcifediol treatment resulted in improved immune function with an increased blood lymphocyte percentage and reduced blood neutrophil-to-lymphocyte ratio compared to the placebo group.[14] An additional retrospective study found that prescription of calcifediol or vitamin D, 15–30 days before hospitalization with COVID-19 infections, was found to improved patient survival in a large retrospective, hospitalized, Andalusian cohort.[15]
In a study, researchers from the Azrieli Faculty of Medicine of Bar-Ilan University in Safed, Israel and the Galilee Medical Center in Nahariya, Israel showed a correlation between vitamin D deficiency and COVID-19 severity and mortality.
The study is among the first to analyze vitamin D levels prior to infection, which facilitates a more accurate assessment than during hospitalization, when levels may be lower secondary to the viral illness. The findings reported build upon results initially published on MedRxiv. The records of 1,176 patients admitted between April 2020 and February 2021 to the Galilee Medical Center with positive PCR tests were searched for vitamin D levels measured two weeks to two years prior to infection.[16]
So, why is there still no mention what-so-ever about the benefits of vitamin D, or any other natural compounds and therapies that might be helpful? For one, there is no money to be made. Over the course of the pandemic, legislators and other government officials have invested heavily in the stock of vaccine manufacturers, and reaped significant financial gains from these investments.[17] Pharma companies have reciprocally poured millions into the campaign of sympathetic congress members.[18] Pharma companies also send large sums of money to the CDC as well.[19] They send money for lobbying to influence the government purchases of their products and resist efforts to render their drugs more accessible or affordable. All said, lawmakers, government officials and agencies, and pharmaceutical companies have all made vast amounts of cash by working together with one another over the course of the pandemic.[20], Keep in mind that each additional round of shots generates billions for vaccine manufacturers. Pharmaceutical companies have a clear stake in multiple rounds being mandated or encouraged for as many people as possible, in as many places as possible (at as high a price as possible). Dr. Fauci is now proposing a 4th shot.[21] It is hard not to see bias in all of this.
“Faith is much better than belief. Belief is when someone else does the thinking.” ~ Buckminster Fuller
Wisdom and Knowledge
Wisdom and knowledge have quite a bit in common. Both words are primarily used as nouns that are related to learning. The word knowledge is defined first as the “acquaintance with facts, truths or principles, as from study or investigation.Wisdom is defined as “the state of being wise,” which means “having the power of discernment and judging properly as to what is true or right: possessing discernment, judgement, or discretion.” It is older (recorded before the 900s), and joins wise and -dom, a suffix that can convey “general condition,” as in freedom. Wisdom is typically gained from experiences and acquired over time. It flows through the sub conscious and conscious mind.
ETMS (Eclectic Triphasic Medical System) – The Mederi Care Medical Approach to health and healing. Synergistic • Unitive • Personalized • Adaptive
Below is a visual aid I created that highlights the importance of “purity of heart” that allows us to free ourselves from bias and seek Truth:
The great Eclectic School of Medicine had a motto: “To Love the Truth, To Prove the Truth, To Apply the Truth, and To Promote the Truth.”
Finding Truth involves wisdom. Wisdom involves an understanding of the nature, source, and limits of knowledge, together with the degree to which we are able to “teotl” (to understand with the Divine Spirit, taken from the Aztec religion).
“The greatest scientists are artists as well,” said Albert Einstein. For Einstein, insight did not come from logic or mathematics. It came, as it does for artists, from intuition and inspiration. Einstein also said, “Imagination is more important than knowledge.“
The Approach of Logical Positivism
Conventional medicine encompasses an inherently restricted set of categories and paradigms for understanding patients and diseases. But given that no single method is suitable for all patients, problems, and situations, this approach is far from optimal.
I propose logical positivism as an alternative to the current dogmatic, narrow view of modern conventional medicine. Logical positivism is spiritual-rationality in the most pristine form. It is considered culturally universal in traditional healing systems, and incorporates traditional wisdom, scientific knowledge, logic, intuition, and prayer, making it applicable to all modalities and situations.
References
[1] Tomás M. León, PhD1; Vajeera Dorabawila, PhD2; Lauren Nelson, MPH1; Emily Lutterloh, MD2,3; Ursula E. Bauer, PhD2; Bryon Backenson, MPH2,3; Mary T. Bassett, MD2; Hannah Henry, MPH1; Brooke Bregman, MPH1; Claire M. Midgley, PhD4; Jennifer F. Myers, MPH1; Ian D. Plumb, MBBS4; Heather E. Reese, PhD4; Rui Zhao, MPH1; Melissa Briggs-Hagen, MD4; Dina Hoefer, PhD2; James P. Watt, MD1; Benjamin J. Silk, PhD4; Seema Jain, MD1; Eli S. Rosenberg, PhD, COVID-19 Cases and Hospitalizations by COVID-19 Vaccination Status and Previous COVID-19 Diagnosis — California and New York, May–November 2021, Weekly / January 28, 2022 / 71(4);125–131, On January 19, 2022, this report was posted online as an MMWR Early Release.
[6] Yu, Y., Esposito, D., Kang, Z. et al. mRNA vaccine-induced antibodies more effective than natural immunity in neutralizing SARS-CoV-2 and its high affinity variants. Sci Rep12, 2628 (2022). https://doi.org/10.1038/s41598-022-06629-2
[16] Patients with vitamin D deficiency (less than 20 ng/mL) were 14 times more likely to have the severe or critical case of COVID than those with more than 40 ng/mL.[16]
With the passing of Thich Nhat Hanh, the Zen Buddhist monk and peace campaigner who brought mindfulness to the West, the world has lost another mentor. Every time we lose someone who helps us live and act in accordance with our highest good, it is a tremendous loss to the world. Martin Luther King. Nelson Mandela. Bishop Desmond Tutu. Thich Nhat Hanh. Orest Bedrij. Although they are no longer on this earthly plane, their inspiration lives on.
Mentors are very important to me. They inspire me to be better in every way. I celebrate their life, I praise their presence and spirit, and I integrate their teachings into the core of my being, so that I can become what God intended me to be.
