Curcumin, what is it exactly?
If you are an enthusiast of traditional Chinese medicine, you must have heard of the famous 【Curcuma longa】. After all, it has thousands of years of historical records and medical use. For example, in the <China Herbal>, turmeric is used to "invigorate the blood, promote the flow of qi, regulate menstruation, and alleviate pain."
Curcuma longa
Curcuma longa, belonging to the ginger family, was initially discovered for its captivating fragrance and used as a mysterious yellow spice. Its earliest recorded use as an herbal medicine also dates back to ancient India. People found that this bright "golden" powder had almost universal healing properties. It was used for some of the most challenging conditions of the time, such as liver disease, stomach ailments, infectious diseases, and various blood disorders (though whether it always cured these ailments is uncertain). After Curcuma longa spread from China to Japan, it became known as a "miracle drug" for alleviating hangovers and pain, especially noted for its surprising effectiveness in treating severe hangovers.
Curcumin's First Appearance
In 1815, after two German scientists first extracted curcumin from Curcuma longa, it was no longer just a spice used in cooking but began to spread globally, reaching far beyond Asia. However, for more than a century after its discovery, curcumin did not have many opportunities to shine because it was considered too "Asian."
Even in 1937, when curcumin was formally used in medical clinical research and published in The Lancet, it remained a supporting player. Over the next 50-plus years, only about 100 papers were published on curcumin, indicating its relatively minor role in scientific research.
Curcumin's Rise to Fame
It wasn't until 1990 that things began to change, and curcumin embarked on a meteoric rise. For instance, between 2015 and 2020 alone, over 6,000 papers related to curcumin were published. To date, there are tens of thousands of research papers on curcumin, including nearly 200 large-scale human clinical trials.
In terms of quantity and scale, curcumin research is now comparable to that of glucans.
This surge in interest can be attributed to two main factors: first, the rapid advancements in life sciences, which have provided new insights into diseases at the cellular and genetic levels, allowing scientists to identify the target genes for curcumin. Second, researchers have gradually overcome the issue of curcumin's low bioavailability in the body, leading to a renewed understanding of its potential health benefits.
In short, the scope of clinical interventions involving curcumin is vast. Current research covers a wide array of conditions, including various cancers (breast cancer, lung cancer, multiple myeloma, prostate cancer, etc.), neurodegenerative diseases like Alzheimer's disease, cardiovascular diseases (atherosclerosis, acute coronary syndrome), skin diseases (vitiligo, psoriasis), inflammatory diseases (gastric ulcers, irritable bowel syndrome, osteoarthritis, ulcerative colitis, bacterial prostatitis, cholecystitis), and metabolic diseases (diabetes, lupus nephritis), among others.
In addition, curcumin has shown potential in intervening in various chronic toxicities, such as heavy metal exposure and alcohol poisoning. Like yeast beta-glucan, curcumin is a seemingly inexhaustible treasure trove of health benefits.
Molecular Mechanisms of Curcumin
Curcumin's wide range of clinical effects can be attributed to its ability to target and regulate numerous genes.
In 2017, scientists from the Anderson Cancer Center and other research institutions jointly published a comprehensive review on curcumin's effects on various chronic diseases. Despite being published seven or eight years ago, the article remains highly relevant and thoroughly explains curcumin's impact on various key genes in our body.
For example, take a look at the diagram below. Although it might seem overwhelming at first, it illustrates the numerous target genes that curcumin can regulate, including but not limited to transcription factors, inflammatory mediators, protein kinases, and various proteins.
Some of the genes involved are Nrf2, NF-κB, MAPK, COX-2, PGE2, FOXO3, VEGF, NOS, among others.
Let's use an example to demonstrate this. The p53 gene is one of the greatest discoveries in the history of cancer research (perhaps even the greatest). In simple terms, it is a tumor suppressor gene (hence called the "guardian of the genome") that controls whether a cell should divide. Thus, p53 is the gene most closely associated with all cancers and tumors. Many effective targeted therapies are closely related to p53.
In tumor patients, the p53 gene is mutated in more than half of cases. Even in people with chronic inflammation and suboptimal health, the expression levels of normal p53 genes are reduced. This is where curcumin comes in handy, as it can enhance the expression of the p53 gene, boosting its surveillance over rogue cells and tumor cells, promoting these cells to enter the apoptosis cycle.
In other words, curcumin likely has the potential to manipulate the tumor switch p53, enabling the activation and suppression of tumor cells.
Clinical Benefits
Anti-inflammatory Effects
Among all its clinical benefits, curcumin's potent anti-inflammatory ability is the most noteworthy and deserves significant attention, surpassing even vitamin C, quercetin, and glucans. It can effectively downregulate various inflammatory cytokines, such as TNF-α, IL-1, IL-6, IL-8, IL-12, MCP-1, and IL-1β, as well as various inflammation-related proteases and transcription factors.
A considerable portion of clinical studies focus on osteoarthritis and rheumatoid arthritis. While we have recommended glucosamine for osteoarthritis due to its ability to modulate the 5-LOX signaling pathway to reduce inflammation, curcumin's clinical applications are much broader.
For instance, a multicenter randomized controlled clinical study showed that taking 1500mg of curcumin daily achieved the same intervention effect as the nonsteroidal anti-inflammatory drug ibuprofen.
There are also numerous clinical studies targeting various gastrointestinal inflammations, such as gastritis, ulcerative colitis, and pancreatitis. Curcumin has shown efficacy in relieving pain, reducing abdominal discomfort symptoms, and preventing recurrence, with intervention doses ranging from 500mg to 2g daily.
Furthermore, curcumin has demonstrated adjunctive therapeutic effects on oral and gingival inflammation in various clinical trials, such as inhibiting the growth of pathogenic bacteria in the oral cavity and preventing gingivitis.
Lowering Blood Lipids
In clinical practice, curcumin is also used as an adjunctive intervention for cardiovascular diseases because it can reduce low-density lipoprotein (LDL) cholesterol, triglycerides, and total cholesterol levels.
Compared to EPA (eicosapentaenoic acid), curcumin's lipid-lowering effect seems to be more extensive. This is because it not only targets LDL cholesterol and triglycerides but also increases the levels of high-density lipoprotein (HDL) cholesterol.
Protective Effect on the Liver
As mentioned earlier, silymarin is an excellent hepatoprotective agent. Similarly, curcumin also exhibits hepatoprotective properties, albeit with a broader spectrum of effects across various organs, unlike silymarin, which primarily focuses on the liver. This versatility might overshadow curcumin's specific benefits for the liver.
Curcumin can address various liver conditions, such as alcohol consumption, medication use, smoking, and various types of fatty liver disease and hepatitis.
For example, curcumin can reduce oxidative stress in liver cells while enhancing mitochondrial function to suppress hepatic inflammatory responses. Oral administration of curcumin encapsulated in nanoparticles can slow down the progression of non-alcoholic fatty liver disease by inhibiting the levels of inflammatory factors.
Intervention for Blood Sugar and Diabetes
Curcumin can act on α-glucosidase and α-amylase, thereby improving insulin sensitivity and enhancing insulin secretion.
In a randomized double-blind, placebo-controlled trial involving 100 patients with type 2 diabetes who supplemented with curcumin for 12 weeks, it was found that fasting blood glucose levels decreased, insulin resistance (HOMA-IR) reduced, and triglyceride (TG) levels also decreased.
In another randomized double-blind, placebo-controlled trial involving 237 prediabetic participants, taking 250mg of curcumin daily significantly reduced HbA1c and fasting blood glucose levels at 3, 6, and 9 months.
Moreover, the diagnosis of type 2 diabetes decreased from 16.9% to 0%. Additionally, compared to the placebo, curcumin treatment significantly reduced HOMA-IR at 6 and 9 months and reduced the elevation of lipoproteins at 9 months.
Prevention and Intervention for Cancer
Firstly, in the case of cervical cancer, both oral and topical applications of curcumin show some efficacy. For instance, a clinical study indicated that daily oral intake of 500-1200 milligrams of curcumin has a significant preventive effect against cervical cancer. Another phase II clinical trial demonstrated that topical curcumin-based products have a good clearance effect on HPV-positive cervical cancer patients.
There are also numerous clinical studies on colorectal cancer. In a clinical trial involving 44 colorectal cancer patients, researchers found that oral curcumin (2 grams or 4 grams daily for 30 days) was effective in preventing colorectal tumors. It increased the curcumin content in the blood and significantly reduced the number of aberrant crypt foci (ACF).
In another clinical trial involving 126 colorectal cancer patients, curcumin substantially reduced the levels of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) in the blood within 2-4 weeks of administration. This was greatly beneficial for both concurrent medication and treatment.
There are numerous cases involving other types of cancer as well. For instance, curcumin can reduce the levels of key factors such as NF-κB, COX-2, and phosphorylated STAT3 in peripheral blood mononuclear cells of pancreatic cancer patients. It can also inhibit the levels of cytokines such as IL-6, IL-8, granulocyte macrophage colony-stimulating factor (GM-CSF), and TNF-α in the bodies of head and neck cancer patients. Additionally, it can enhance drug sensitivity and reduce adverse reactions in breast cancer patients, among other effects.
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