Curcumin is the primary bioactive compound in the turmeric (Curcuma longa) — it is the yellow pigment that gives the turmeric its characteristic colour, and it is one of the most extensively studied and most potent natural anti-inflammatories in the world. The curcumin has been used in the traditional Indian Ayurvedic medicine for over 5,000 years for the treatment of the inflammatory conditions, of the digestive disorders, and of the skin diseases, and it is now the subject of over 12,000 peer-reviewed scientific articles and over 100 clinical trials. The curcumin exerts its anti-inflammatory effects primarily through the inhibition of the NF-kappaB signalling pathway — it prevents the phosphorylation and the degradation of the I kappaB (the inhibitory protein that keeps the NF-kappaB in the cytoplasm in the inactive state), it inhibits the translocation of the NF-kappaB to the nucleus, and it prevents the binding of the NF-kappaB to the DNA in the nucleus, thereby blocking the transcription of the inflammatory genes. The curcumin also inhibits the cyclooxygenase-2 (COX-2), the lipoxygenase (LOX), and the inducible nitric oxide synthase (iNOS) enzymes, reducing the production of the prostaglandins, the leukotrienes, and the nitric oxide — all of which are inflammatory mediators that are chronically elevated in the inflammatory conditions and that drive the tissue damage and the symptoms of the inflammatory diseases. Without adequate curcumin and its potent anti-inflammatory effects, the chronic inflammation develops and persists, the metabolic syndrome progresses, and the neurodegeneration accelerates — the hallmark of the curcumin deficiency and of the chronic inflammatory state that underlies the modern chronic disease burden. The typical dietary curcumin intake from the turmeric is 2-5mg daily (from the curry powder, the turmeric tea, and the culinary turmeric), and the therapeutic doses for the anti-inflammatory effects are 500-2000mg daily of the standardised curcumin extract (which contains 95% curcuminoids, including the curcumin, the demethoxycurcumin, and the bisdemethoxycurcumin).
Curcumin and the Metabolic Syndrome
The metabolic syndrome is the cluster of the metabolic abnormalities that includes the central obesity, the insulin resistance, the dyslipidaemia (elevated triglycerides, low HDL cholesterol), the hypertension, and the chronic inflammation — and it is one of the most important risk factors for the type 2 diabetes, the cardiovascular disease, and the non-alcoholic fatty liver disease (NAFLD). The curcumin has been shown in multiple RCTs to improve all of the components of the metabolic syndrome — it reduces the fasting blood glucose, reduces the HbA1c, improves the insulin sensitivity (as measured by HOMA-IR), reduces the triglycerides, reduces the LDL cholesterol, reduces the blood pressure, reduces the waist circumference (a marker of central obesity), and reduces the inflammatory markers (CRP, IL-6, TNF-alpha) in people with the metabolic syndrome and with the type 2 diabetes. The mechanism of these metabolic effects involves the activation of the AMPK (AMP-activated protein kinase, the master regulator of the cellular energy metabolism), the inhibition of the NF-kappaB (the master regulator of the inflammatory gene expression), and the modulation of the adipokine secretion from the adipose tissue — reducing the leptin resistance and the adiponectin deficiency that are the hallmarks of the metabolic syndrome and that drive the insulin resistance. A meta-analysis of 16 RCTs in over 1000 participants found that the curcumin supplementation at 300-1000mg daily significantly reduced the fasting blood glucose (by 10-15mg/dL), reduced the HbA1c (by 0.5-1.0%), reduced the triglycerides (by 15-20mg/dL), and reduced the CRP (by 2-3mg/L) — making the curcumin one of the most effective nutritional interventions for the management of the metabolic syndrome and of the type 2 diabetes.
Curcumin and the Neurodegeneration
The curcumin has also been studied extensively for its neuroprotective effects in the neurodegenerative diseases — including the Alzheimer’s disease, the Parkinson’s disease, and the Huntington’s disease. The mechanism of these neuroprotective effects involves the inhibition of the NF-kappaB (which reduces the neuroinflammation that is a primary driver of the neurodegeneration), the inhibition of the beta-amyloid aggregation and the promotion of the beta-amyloid clearance (which is the primary therapeutic target in the Alzheimer’s disease), the inhibition of the tau phosphorylation (which is the other primary pathological hallmark of the Alzheimer’s disease), and the activation of the Nrf2 transcription factor (which induces the expression of the antioxidant and the detoxification enzymes that protect the neurons from the oxidative stress). The curcumin’s ability to cross the blood-brain barrier and to accumulate in the brain makes it particularly useful for the prevention and the treatment of the neurodegenerative diseases — and it is one of the most promising natural compounds for the prevention of the age-related cognitive decline and of the Alzheimer’s disease.
Practical Application
For general curcumin supplementation for the anti-inflammatory and metabolic support, the evidence-based approach is to supplement with 500-1000mg of standardised curcumin extract daily (containing 95% curcuminoids, with the addition of the piperine at 5mg to enhance the bioavailability by 2000%). The curcumin is poorly absorbed (only 1-2% of the oral dose is absorbed without the piperine enhancement), and the addition of the piperine (from black pepper, at 5-10mg) is therefore essential for the adequate bioavailability and for the therapeutic effect. The curcumin is generally well-tolerated with no significant adverse effects at doses up to 2000mg daily, though very high doses may cause the gastrointestinal symptoms (nausea, diarrhoea). For comprehensive anti-inflammatory and antioxidant support, curcumin pairs well with the quercetin (which has complementary anti-inflammatory effects and which inhibits the NF-kappaB through a different mechanism than curcumin), with the gingerol (from ginger, which has complementary anti-inflammatory and anti-nausea effects), with the omega-3 fatty acids (which have anti-inflammatory effects through the resolvins and the protectins and which work synergistically with the curcumin for the reduction of the chronic inflammation), and with the vitamin D (which has immunomodulatory effects and which is increasingly recognised as an important determinant of the inflammatory status and of the metabolic syndrome).
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