Curcumin

Curcumin is the main bioactive component of turmeric, an Eastern orange culinary spice that has been used for millennia by ancient healing modalities for its therapeutic properties and revitalizing effects.

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Curcumin is the principal curcuminoid of turmeric and carries powerful antioxidant, anti-inflammatory, and chemopreventive benefits.

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It was firstly isolated in 1815 as a yellow / orange pigment from the rhizomes of the Curcuma Longa L. plant, which has been a staple in Ayurvedic and Traditional Chinese Medicine (TCM) as a digestive bitter and blood invigorator [9].

Along with other spices that are “energetically warming”, such as cinnamon or cloves, turmeric is said to aid in blood circulation problems that are common in many pathological conditions, such as cardiovascular disease (CVD) and menstrual irregularities.

Curcumin exerts its pro-healthy effects via modulating gene expression and suppressing inflammatory processes that damage cells, as well as stimulating the body’s innate detoxification pathways [10].

Its overall immunosuppressive and health-promoting effects with regards to a wide variety of ailments are remarkable, even from a pharmacological point of view [11]

Neuroprotective Benefits of Curcumin

Curry, the popular Indian culinary spice is also rich in turmeric, indicating a possible positive correlation with the fact that until recently India had statistically one of the lowest rates of inflammatory diseases in the world [12].

Particularly low was the incidence of neurocerebral diseases, such as Alzheimer’s disease and Parkinson’s.

Alzheimer’s is the most common form of dementia in elderly individuals and the sixth leading cause of death in the United States [13].

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It is an age-dependent neurodegenerative disease characterized by progressive cognitive deterioration, memory loss, and changes in behavior and personality.

Research has shown that curcumin may carry a strong preventative and curative effect on brain disorders, such as Alzheimer’s disease [14].

If sufficient amounts of curcuminoids – the active biomolecules of turmeric with curcumin being the primary – reach the brain, they hinder the action of two abnormal protein groups known as beta-amyloid plaque and Tau protein [1].

Due to its lipophilic properties (ability to dissolve in fats and oils), curcumin can cross the blood-brain barrier, binding to amyloid deposits and escorting them out of the body through the urine or feces [15].

A 2014 scientific review showed that the soluble beta-amyloid and Tau proteins commonly found in the brain of Alzheimer’s patients work synergistically to drive healthy neurons into a diseased state [2].

Several research papers have also revealed that curcumin promotes the disaggregation of existing amyloid deposits and prevents the accumulation of new.

In conjunction with Vitamin D, curcumin exposes these substances to our immune system, specifically the macrophages, which through a process known as phagocytosis destroy these protein deposits [16, 17].

Vitamin D, widely known as calciferol, is a vitamin/pro-hormone that carries enormous significance in immune system regulation and calcium homeostasis [3].

Additionally, it is an essential component of many alternative healing protocols for the treatment of autism and AIDS [18, 19].

Recently, a research study conducted in rats showed that Vitamin D and specifically its biologically active form known as calcitriol, inhibits cancer cell proliferation and retards tumor growth, suggesting its potential role as a cancer-fighting agent [20].  

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Another animal study conducted on rats that were deliberately put on a chronic unpredictable stress protocol (CUS), showed that curcumin is able to ameliorate all negative side effects corresponding with random, intermittent and unpredictable exposure to various stressors [6].

Chronic unpredictable stress protocols have been consistently shown to induce behavioral and immunological alterations in most mouse strains, including depressive-like behavior, sucrose addiction, impaired memory, learning, and cognitive function.

Curcumin achieved that by increasing brain-derived neurotrophic factor (BDNF) and extracellular signal-regulated kinase-1 (ERK1) levels in the hippocampus area of the brain.

BDNF is a protein that acts as a neuron growth hormone, encouraging neurogenesis and protecting already existing nerve cells from dying off [21].

ERK1 is an important regulator of various bodily processes, including inflammation, metabolism, cell death and survival [22].

ERK1 along with its chemically similar sibling ERK2, are abundant in brain tissue and have been found to greatly affect brain health; they regulate synaptic plasticity, brain development and repair, and memory formation [7].

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The ERK family also constitutes potent mediators of neuronal death and neuroinflammation in many diseases of the Central Nervous System (CNS), including Amyotrophic Lateral Sclerosis (ALS), Parkinson’s disease, Alzheimer’s disease, and stroke [23, 24, 25, 26, 27].

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Curcumin promotes the disaggregation of existing amyloid deposits in the brain and prevents the accumulation of new.

Curcumin Exhibits Poor Bioavailability

turmeric black pepper

It is well documented that curcumin has a strong positive impact on many pathological conditions including cardiovascular, respiratory, infectious, metabolic, and neurological diseases, as well as cancer.

However, it’s absorption and bioavailability are limited, creating doubts on whether it can be considered an actual potent therapeutic agent.

The speculated mechanisms for its suboptimal cellular uptake and pharmacokinetic profile are: 1) Low intestinal absorption [29] 2) It’s rapid metabolism [28] 3) It’s hydrophobic nature (it repels water molecules) [30].

Since curcumin is characterized by low water solubility, it should always be ingested with fats and oils, which have been shown to increase tissue absorption and delivery [31]

Accordingly, dietary fats are not the only substance improving curcumin’s intestinal absorption.

One of the active components of black pepper called piperine, a potent alkaloid, also does.

Piperine, also known with trademarked name BioPerine, is famous for its positive benefits on intestinal permeability (leaky gut) and digestive health.

Piperine increases tissue uptake of many difficult-to-absorb curcuminoids (including curcumin) by up to 2,000% [32]

Curcumin with BioPerine

Thus, curcumin should ideally be taken with meals rich in overt fats, and/or black pepper.

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If the dish is low-fat, adding condiments, such as butter, ghee, or organic extra virgin olive oil will help with absorption.

Differently, its activity is largely mitigated by the liver, ending up being excreted through the kidneys and colon.

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Thankfully, there are many exceptional dishes to add curcumin in, which in itself enhances their flavor and deliciousness.

Turmeric chicken and rice or curried cauliflower soup are two of the many delectable curcumin-rich, anti-inflammatory recipes you may execute at the comfort of your own home.

The Benefits of Curcumin on Weight Loss

A recent meta-analysis indicated that regular curcumin consumption resulted in a detectable reduction in weight, body mass index (BMI), waist circumference, leptin levels, and a significant increase in adiponectin levels [8].

Adiponectin, as its name implies, is an adipose tissue-derived, anti-inflammatory protein/hormone involved in glucose regulation and fatty acid breakdown. 

Low adiponectin levels, typically present among obese individuals, may reflect a dysfunction in adipose tissue, which many people forget that is a metabolically dynamic organ.

Adipose tissue acts as an endocrine organ producing a diverse array of biochemical compounds that regulate metabolic function.

Low serum adiponectin levels are associated with: 

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  • Increased inflammation [34]
  • Lipid abnormalities [35]
  • Insulin resistance [33]
  • Increased risk of diabetes [36]
  • Non-alcoholic-fatty-liver (NAFLD)
  • Coronary heart disease [39, 40]
  • Increased risk of cancer [37, 38]
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Simply put, adiponectin is a key regulator of insulin sensitivity and reduced tissue inflammation.

Thus, curcumin may constitute an excellent dietary addition in individuals suffering from metabolic syndrome and obesity. 

Separate studies have also shown that curcumin appears to increase both circulating adenosine monophosphate (cyclic AMP or cAMP) and PGC-1, a protein that plays a key role in energy metabolism [41].

The significance of this is that cyclic adenosine monophosphate (cAMP) is directly linked to fat mobilization from adipocytes (fat cells) and PGC-1 promotes the development of new mitochondria (mitochondrial biogenesis) [46, 47].

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Mitochondria are strange, semi-autonomous, ovoid-shaped cellular organelles that act as the power plants of cells.

They consist of two membranes, one inner and one outer, made up of phospholipid bilayers and proteins.

Due to their semi-dependent nature, they carry their own genome, which indeed shows substantial similarity to bacterial genomes and offers them the ability to replicate on their own [48].

Their inner membrane is not smooth like the outer, but folded and compartmentalized.

This is where ATP (adenosine triphosphate) is produced and the majority of fatty acid oxidation is taking place, through a process called beta-oxidation.

mitochondria curcumin
Anatomy of mitochondria

Consequently, both molecules increase fat loss and intracellular energy production, critical elements for curing metabolic diseases.

Exercise in itself, especially endurance-type exercise, can increase both cAMP and PGC-1, but animal studies show that pre-workout curcumin ingestion induces a further elevation in these molecules [4].

Animal research may not necessarily prove that these effects are also applicable to humans, but contributes positively to the acquisition of information and the development of sophisticated testing techniques.

Mechanism of Action

Curcumin is part of the ginger family (Zingiberaceae), which also exhibits strong anti-inflammatory properties, with the most known being the alleviation of gastrointestinal conditions and dyspepsia (indigestion) [49, 50]

Being a powerful polyphenolic compound like the famous resveratrol, curcumin exerts its anti-inflammatory and antioxidant effects both directly and indirectly.

In other words, curcumin does not behave just like a classic antioxidant by donating electrons, scavenging free-radicals, and protecting cellular components sensitive to oxidative damage (like the vitamins C or E), but also acts hormetically [42, 43, 44].

Hormesis refers to a compound’s ability to stimulate – rather than inhibit- a system when an optimal dose is being administered (i.e. a toxic substance is beneficial in small amounts) [45].

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What this means is that curcumin, by minorly stressing and stimulating our body’s innate immune system, induces an overall positive systemic health effect.

As a response to the minor stress, the immune system ends up working better, leading to the successful neutralization and expulsion of various harmful substances

These may include xenobiotic compounds, heavy metals, steroid hormones, aggregated proteins, or pathogenic microorganisms (i.e. bacteria, yeast, fungi, viruses, etc.)

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Polyphenols, including curcumin, can modulate gene expression and improve the body’s endogenous antioxidant enzymatic defense system, leading to enhanced immunity [51].

Fruits, vegetables, cacao, black coffee, green tea, and herbs are the best sources of polyphenols.

A big part of curcumin’s antioxidant and anti-inflammatory properties is attributed to the upregulation of peroxisome proliferator-activated receptor-γ (PPAR-γ), a master regulatory molecule of adipogenesis (creation of fat cells), glucose homeostasis, and lipid metabolism [52]

PPAR-γ plays a substantially important role in the immune response, by inhibiting the expression of inflammatory cytokines and directing the differentiation of immune cells towards anti-inflammatory morphological types [53].

Another major way curcumin mitigates uncontrolled inflammation is by regulating the activity of a protein called Nuclear Factor Kappa-B (NFK-B) [54].

This protein is considered to be a potent chemical promoter of inflammatory reactions in the body, and among other effects can lead to increased production of inflammatory cytokines (inflammation signaling molecules produced by immune cells) [55].

By limiting the activity of Nuclear Factor Kappa-B (NFK-B), curcumin further suppresses the activity of other inflammatory enzymes, such as cyclooxygenase-2 (COX-2) and metalloproteinase-9 (MMP-9) [56, 57].

In simple words, there is a prolonged domino-effect of inflammatory processes being shut down by curcumin’s activity in the body.

By minorly stressing and stimulating our body’s innate immune system, Curcumin induces an overall positive systemic health effect.

Additional Benefits of Curcumin

Apart from the aforementioned health benefits, curcumin is equally powerful as an analgesic agent, reducing pain very effectively and being extensively used for the treatment of chronic inflammatory conditions, such as rheumatoid arthritis and fibromyalgia [58, 59].

It also exhibits anti-thrombotic and anti-atherogenic effects on the arterial endothelium, promoting the maintenance of its elasticity and reducing the chance of atherosclerotic plaque formation [60, 61].

Some scientists have argued that even if curcumin’s intestinal absorption is sub-optimal, its mere presence in the gut may provide anti-inflammatory benefits in chronic gastrointestinal conditions, such as leaky gut syndrome and irritable bowel disease (IBD) [62, 63].

Conclusion

Curcumin carries a multifunctional role in human health exerting positive health benefits in multiple organ systems, including the musculoskeletal and digestive systems.

It’s not coincidental that most ancient, natural remedies of Eastern medicine include curcumin as a primary means of disease prevention and restoration of health. 

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Liberal consumption of curcumin can be proven beneficial for the majority of the population.

According to a systematic review published in 2020, “Humans appear to be able to tolerate high doses of curcumin without significant side-effects[5].

Consequently, its consumption is highly recommended, even in supraphysiological dosages, for most healthy individuals.

Concerning dosage, a daily intake of one tablespoon of organic turmeric or 1.000 mg of pure curcumin along with black pepper, either mixed in a glass of water or added in food, seems to be ideal.

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About George Kelly

George Kelly M.Sc. is a Registered Dietitian Nutritionist that specializes in chronic and autoimmune conditions. He is the CEO and lead author of Metabolic Body.


References

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