Curcumin

Curcumin

Curcumin is one of the most commonly used and best-studied epigenetic agents. It has a very strong and, moreover, significantly broad-spectrum action. It influences a huge number of processes in the body related to our health, physical and mental condition and helps in a number of diseases and ailments.

Description

It is a yellow plant dye from the flavonoid group found in the turmeric root of the turmeric tree, a plant in the ginger family. The curcumin content of turmeric is around 3%.

History

Turmeric is a traditional part of the spice curry, which has been used for more than 4000 years, especially in Indian cuisine and traditional Indian medicine – Ayurveda. In Hindu ceremonies, it symbolized the sun, protection and wealth. Curcumin was first isolated from turmeric two hundred years ago. Today it is also used as a food colouring.

Healing effects

The use of curcumin in traditional medicine is very wide. It has a beneficial effect on the digestive system – improves digestion, liver and gallbladder function, increases the production of gastric juices, has anti-inflammatory, antibacterial and antiviral effects, is used for painful menstruation, cardiovascular diseases, jaundice, and externally to disinfect wounds. It supports immunity, regeneration, relieves pain, slows the aging process and is used as a general stimulant. From an Ayurvedic perspective, it is also slightly warming and soothing, nourishes all tissues, and promotes everything related to circulation – not only physical movement, but also the flow of thought.

Modern science has focused primarily on the epigenetic effects of curcumin. There are a number of factors that influence our health that, although they cannot change our genetic information, can influence which genes that affect our health and fitness will eventually be expressed through a number of chemical processes – for example, our diet, stress levels, environment, etc. And curcumin is one of the substances that can influence the processes that affect our DNA, specifically the intensity of biochemical reactions that increase or decrease the activity of individual genes in DNA (i.e. in particular gene methylation, histone acetylation and regulation by microRNAs). In addition, curcumin combines its epigenetic effect with an extremely strong antioxidant and anti-inflammatory effect.

Other important mechanisms of action of curcumin are its anti-inflammatory activity and its ability to positively influence the gut microbiome, the balance of which is crucial for the proper functioning of virtually the entire body. It helps to maintain the correct ratio of ‘friendly’ to pathogenic bacteria, positively influences the permeability of the intestinal barrier and reduces inflammation in the gut.

Curcumin also has a positive effect on mitochondria – it promotes the formation of new mitochondria and improves the function and protection of existing ones. Mitochondria are the organelles in which nutrients are converted into energy, and their health is therefore essential for the functioning of virtually all organs and tissues of the body, as well as for the speed of ageing and athletic performance.

Anti-tumour action

Curcumin is one of the natural substances with the strongest anti-cancer activity – it has been shown that people who consume higher doses of turmeric in their diet have a lower incidence of cancer.(2) This is partly due to its strong antioxidant potential, but more importantly is its epigenetic action. Although curcumin cannot directly affect our DNA, it does act through epigenetic mechanisms (DNA methylation, acetylation, histone modification, microDNA changes, etc.) to decide which genes will eventually be expressed and which will not, which includes the genes responsible for cancer (1).

The effect of curcumin on reducing the risk of cancer has been confirmed in a number of studies (3, 4). The most important mechanisms of its action include modification of proteins called histones, which are involved in the spatial arrangement of DNA molecules. It is this abnormal activity that has been shown to be associated with a higher risk of cancer (5, 6, 7).

Another important mechanism of action of curcumin is to affect the so-called DNA methylation, a process that prevents the expression of certain genes – a certain stretch of DNA is still present, but the body cannot “read” it. Two types of methylation have been found in cancer cells, which cause the body to lose control of the tumour.(9) Several studies have confirmed the ability of curcumin to influence the methylation process (11, 12).

However, curcumin also has an effect on microRNAs, which are short-chain compounds (about 20 nucleotides) that are not involved in protein formation but play an important role in programming cell death and thus influence the formation of cancer cells.(13) It is through its effect on microRNAs that curcumin can influence the proliferation of cancer cells.(14)

The beneficial effects of curcumin have been confirmed in a number of cancers, including breast, prostate, lung, colon and pancreatic cancer.

Cardiovascular disease

As with cancer, the epigenetic action of curcumin plays an important role in the prevention and treatment of cardiovascular disease.

However, its anti-inflammatory action is also key, because inflammation plays a very important role in the development of cardiovascular diseases – it damages the cells of the blood vessel wall, which subsequently allows the formation of atherosclerotic plaques. Curcumin significantly reduces the production of inflammation-promoting substances such as TNF-α, cytokines and the enzyme COX-2. In addition, it affects the activity of enzymes involved in lipoprotein metabolism, which in turn results in a reduction in blood cholesterol and triglyceride levels. A major benefit may also be the promotion of nitric oxide production, which causes blood vessels to dilate, thereby improving blood flow to all tissues in the body. (15, 17, 57)

Immunity and antimicrobial action

Curcumin is a very powerful immunostimulant. It promotes the formation and differentiation of a wide range of immune cells (B-cells, T-cells, macrophages, dendritic cells, NK cells…) and has a beneficial effect on both innate and acquired immunity. In doing so, it strengthens the immune response not only to infection-causing microbes, but also to cancer cells. Its anti-inflammatory action is also important here. It also helps to alleviate allergies. (100)
In addition, curcumin has a direct antimicrobial effect on a number of pathogens. In particular, its ability to inhibit the multiplication of a wide range of viruses, such as influenza, hepatitis (type A, B and C), Herpes Simplex 2 virus, arboviruses (e.g. It also works against a large number of bacterial strains, including golden staphylococcus, K. pneumoniae, and E. coli. It also works against 19 different types of fungal infections, including the yeast Candida albicans and food molds (96-98, 100).

Autoimmune diseases

Autoimmune diseases are diseases in which, in simple terms, the immune system attacks its own tissues. Heredity plays a role in the development of all of them, but epigenetic processes also play a major role – especially those related to the formation and functioning of immune cells, the production of inflammatory cytokines and the COX-2 enzyme, and the specific behaviour of the cells of the affected tissues (e.g. in terms of apoptosis or cell death). In virtually all autoimmune diseases, significant variations in gene methylation, histone acetylation and microRNA regulation have been demonstrated. The state of the gut microbiome also plays a major role (56).

Curcumin has significant anti-inflammatory, immunomodulatory and anti-degenerative effects and is therefore very effective in virtually all autoimmune diseases, whether Crohn’s disease (56), ulcerative colitis (49, 56), rheumatoid arthritis (55), Bechterew’s disease, diabetes I. type I, autoimmune thyroid disease (50), lupus (51), multiple sclerosis (55) and many others. Particularly in inflammatory bowel disease, its effects on the gut microbiome and gut wall permeability are also beneficial.(56) Also important here is the ability of curcumin to positively affect the balance of the gut microbiome, which is almost always disturbed in autoimmune diseases.(94)
Dosage varies from disease to disease. It is relatively high, for example, in ulcerative colitis, where doses as low as 2 000 mg per day were effective (significant improvement in the condition after only 4 weeks of use), while doses of around 450 mg did not bring any improvement. (51) In rheumatoid arthritis, on the other hand, one study showed significant improvement after 12 weeks of only 66.3 mg of curcumin. (54) Low doses, namely 80 mg per day, were also effective in multiple sclerosis, but these were given to patients in this study over a long-term period of 26 weeks.

Lupenka

The effectiveness of curcumin has also been demonstrated in severe forms of psoriasis. Here too, its strong anti-inflammatory action is probably the reason.(91)

Hair fall

One of the main causes of hair loss in men (so-called androgenic alopecia) is considered to be the hormone dihydrotestosterone (DHT), which is produced in the body from the male sex hormone testosterone. For this conversion to occur, the action of an enzyme called 5α-reductase is required. This fact is exploited by classical medicines (e.g. Finasteride), which aim to inhibit 5α-reductase, but their disadvantage is the possible occurrence of unpleasant side effects, in particular a reduction in erectile capacity, loss of libido or depression (41).

However, research has shown that curcumin has the same ability. Although its potency is slightly lower than that of the drug, 1 g of turmeric extract has the same potential to inhibit 5α-reductase as 13 mg of Finasteride, but has no negative side effects even with long-term use (42).
Curcumin, however, also counteracts hair loss in other ways. For example, it mitigates the negative effects of stress, which is another significant risk factor for alopecia in both men and women (43). It also helps to activate so-called DVR receptors, which are receptors on the cell nucleus for vitamin D. Although vitamin D alone does not prevent hair loss, genes activated through VDR receptors trigger the production of proteins that act as control signals in the hair growth process, again in both sexes (44).

Prostate enlargement

The aforementioned hair fall is not the only unpleasant effect of dihydrotestosterone. This hormone also contributes significantly to the development of benign prostatic hyperplasia. In this problem, which is particularly familiar to men in their fifties and above, the prostate gland, the gland that surrounds the urethra, becomes enlarged. The prostate gland is oppressed by this enlargement and the result is frequent and difficult urination.

Therefore, the ability of curcumin to block the formation of 5α-reductase, and thus the formation of dihydrotestosterone, is also very useful in this case. The effects on the prostate here are similar to those of Finasteride (45).

Diabetes

Diabetes mellitus is another of the many diseases of civilisation in which inflammatory processes play an important role. Curcumin has a pronounced anti-inflammatory effect, improving the function of insulin-producing beta-cells and preventing their destruction. Animal studies have also shown that it reduces insulin resistance.(21-27) Of great importance for diabetics is the ability of curcumin to promote the production of the enzyme AMPK, which is essential for the absorption of glucose from the blood into the muscles and its use within muscle cells. Muscles are the most important “processor” of glucose and if the AMPK enzyme is used more efficiently in the muscles, the result is a reduction in blood glucose levels. (52, 53) Daily doses as low as 300 mg have been shown to be effective in studies.

Animal experiments also show that curcumin may also be useful in preventing and treating complications of diabetes. For example, when scientists administered it to diabetic mice suffering from severe limb ischemia (inadequate oxygen supply due to poor blood vessels), they experienced significant improvements in blood circulation and increased blood capillary density in the limbs (95).

Arthrosis

Osteoarthritis is a degenerative joint disease characterised by significant loss of cartilage, followed by inflammatory processes that cause pain and further damage to joint structures. It is often considered a purely mechanical problem, but research shows that this is not the case. Articular cartilage has a high capacity for regeneration, and epigenetic processes play a major role in determining whether it is damaged.

The process of methylation, which affects the biology of cartilage cells called chondrocytes, probably plays the biggest role. When scientists examined the DNA of damaged and undamaged areas of cartilage in people with mild and advanced arthritis, they found more than a thousand differences in the methylation of genes. Further research then revealed changes in the methylation of more than a third of the genes that increase susceptibility to arthritis in patients. Significant variations were also confirmed in transcription factors, which are essential in the process of “reading” genes, and in the production of cytokines, which are involved not only in inflammatory processes but also reduce the production of type II collagen and reduce cartilage elasticity (46, 47).

Curcumin can significantly help reduce pain in arthritis – its anti-inflammatory and pain-relieving effects are comparable to non-steroidal antirheumatic drugs such as aspirin or ibuprofen. One study showed that a daily dose of 2 000 mg of curcumin had the same effects as 800 mg of ibuprofen (52), but quarter-size doses were also effective in studies (51). In particular, curcumin reduces the production of the enzyme COX 2 or the transcription factor NF-κB, which is important for reducing the rate of inflammatory processes. However, due to its antioxidant and epigenetic effects, it also protects chondrocytes (cartilage cells) and restores the production of type II collagen.(48) The combination of curcumin with boswellia has been shown to be particularly effective.(51)

Obesity

The basis of any successful weight loss is, of course, the adjustment of the energy balance so that the energy expenditure outweighs the energy intake. However, obesity is always accompanied by a certain level of inflammatory processes in the body and therefore anti-inflammatory substances such as curcumin can play a very positive role in its treatment (29-31).

However, obesity has an epigenetic component – epigenetic changes such as DNA methylation or histone modifications in genes responsible for adipose tissue formation, inflammatory processes or insulin production are always present in the genetic information of obese people. Curcumin is one of the substances whose positive effect on obesity is relatively well documented. It affects the function of genes responsible for energy metabolism and fat storage. (32-34)

Curcumin may also contribute to successful weight loss through its positive effect on mitochondria. Since mitochondria are where nutrients are converted into energy, their dysfunction reduces overall energy expenditure (95).

Mental performance

When researchers in one study gave volunteers turmeric powder containing 80 mg of curcumin, they experienced a significant improvement in mental performance an hour later. In particular, their ability to concentrate and working memory efficiency improved, but they also had better moods, higher levels of satisfaction and lower levels of fatigue due to mental stress. (58)

Alzheimer’s and Parkinson’s disease

The first stage of the development of these diseases is the clumping of proteins that subsequently damage the synapses of nerve cells. According to research by scientists at Michigan State University, curcumin can effectively prevent this clumping. (35)

However, epigenetic changes, particularly DNA methylation and histone modifications, also play an important role in Alzheimer’s disease, resulting in significant impairment of memory, mental performance and other symptoms of the disease. (36, 37) And, as in the previous diseases mentioned, curcumin is one of the natural substances that can counteract these changes. (38, 39)

Sports performance

Curcumin is one of the substances that can greatly benefit athletes, both endurance and speed-strength athletes. Again, its anti-inflammatory action is very important here, as strenuous training causes microscopic damage to muscle fibres, resulting in the development of inflammatory processes. These are then the cause of pain and deterioration of strength. By reducing muscle inflammation, curcumin also reduces muscle soreness and speeds up the entire recovery process. The athlete is then able to undergo further strenuous training sooner, which in time will have a positive effect on his performance (57).

Athletes of all disciplines can also greatly benefit from curcumin’s ability to improve the bioavailability of nitric oxide and protect this molecule from free radical degradation. As we mentioned above, nitric oxide dilates blood vessels and improves blood flow to tissues, including muscle tissue, resulting in increased endurance and strength performance. For example, the researchers tested a group of adults who were given 2,000 mg of curcumin daily for 12 weeks and examined the differences in blood flow in the major artery in the upper arm. The result was surprising: blood flow increased by an average of 34% (62).
Endurance athletes in particular may also benefit from curcumin’s ability to promote the production of the enzyme AMPK. This enzyme allows glucose to be absorbed more efficiently from the blood into the muscles and used within the muscle cells, which is appreciated not only by the aforementioned diabetics but also by endurance athletes, who can gain more energy for their working muscles.

In addition, curcumin’s ability to improve mitochondrial formation and function also helps to support athletic performance. In fact, when it is used, the formation of mitochondria in muscle cells is accelerated. As a result, the muscles are supplied with more energy, which results in improved athletic performance. (95)

Liver

Curcumin also has a hepatoprotective effect, i.e. the ability to protect liver cells from damage. It combines its antioxidant and anti-inflammatory properties. It protects the liver against the effects of alcohol, toxic substances and the side effects of drugs, while also supporting liver regeneration in the event of damage. It also counteracts fatty liver and liver fibrosis and cirrhosis (90).

Depression and anxiety

The dye from turmeric root is also known to have positive effects on the psyche, both for depression and anxiety. It effectively influences the rate of histone acetylation and gene methylation, improves the production of the growth factor BDNF and repairs damage to mitochondria, whose impaired function may also contribute to depression. Its anti-inflammatory action is also implicated here, as psychiatric problems usually have a higher rate of inflammatory processes in the brain. (92)

Curcumin also helps relieve symptoms of anxiety (59), post-traumatic syndrome (59) and reduces the rate of effects of chronic stress on brain function (61).

Endometriosis

Endometriosis is one of the most common gynaecological diseases. It causes migration of the uterine lining outside the uterus, which causes inflammation and intense pain, especially during menstruation. Curcumin can help here thanks to its anti-inflammatory and analgesic effects. In addition, it limits the formation of new blood vessels, which are essential for the supply of blood to the endometrial deposits. In experiments on mice, the reduction of uterine mucosal deposits after curcumin administration has been directly confirmed. Its advantage here is the minimal incidence of side effects and the possibility of long-term use. (93)

Ageing

Some research shows that curcumin can help slow down aging. Although it has no direct effect on the lifespan of cells and their transition to senescence, it is one of the most effective activators of sirtuins, which are enzymes that slow down the ageing process, especially through their effect on mitochondrial function. Dysfunction of the mitochondria impairs the function of all organs and tissues and thus accelerates ageing. The extensive epigenetic action of curcumin is also important here, as the rate of ageing is fundamentally influenced by the level of gene methylation and the state of chromatin, both of which are significantly positively affected by curcumin. In addition, in animal experiments, adding curcumin to the diet led directly to a prolongation of life. In addition, it mimics the beneficial effect of calorie restriction and moderate physical activity on the rate of ageing. Its anti-inflammatory action also plays a positive role, as does its ability to act as a regulator of autophagy (a process whereby a cell ‘eats’ itself, which has a positive effect on its function). As we have already mentioned, although it does not directly affect the amount of senescent cells (their accumulation in the body is also one of the causes of aging), it does help to reduce the inflammation that takes place in the body as a result of the accumulation of senescent cells (95).

Thyroid gland

Curcumin has a significant positive effect in both hypofunction and hyperfunction of the thyroid gland. It also has a great effect in autoimmune disorders – it has an immunomodulatory effect, and it is a strong anti-inflammatory substance that regulates the production of the inflammatory enzyme COX-2 and other substances involved in the course of inflammatory processes in the thyroid gland (NF-kB, TNF-alpha and others). It also acts as an antioxidant that protects the cells of the thyroid gland and has a preventive effect against cancer of this organ (99).

Use, contraindications, combinations

Curcumin can be consumed as part of a normal diet – turmeric, which contains this substance, is part of the spice curry, for example. The other option is to take it in the form of dietary supplements. However, the main problem here is the limited absorption of curcumin, which is mainly due to its limited solubility in water – it is much more soluble in fat. A suitable way to improve the bioavailability of curcumin is to consume a dietary supplement or spice along with a higher-fat meal or omega-3 fatty acids.

Another way to improve the bioavailability of curcumin is to take it together with substances that promote absorption. Perhaps the most well-known of these is piperine, which is a component of pepper. The concentration of curcumin in the blood plasma is up to 2 000 % higher when taken with piperine than when consumed alone (other studies show that blood levels of curcumin increase up to 30 times when taken with piperine). Incidentally, pepper is also one of the important components of the curry blend. Another effective option is to combine it with quercetin (here the bioavailability is improved by an average of 147%) or resveratrol. Also interesting is the combination with butyrate, which is a product of certain gut bacteria also used as a dietary supplement. Butyrate helps curcumin to cross the blood-brain barrier separating the brain from the bloodstream, which may increase its effectiveness in depression, neurodegenerative diseases and other brain-related problems. (40, 65, 66, 68, 95)

Curcumin is generally well tolerated, even in very high doses. Clinical studies have even confirmed the safety of extreme daily doses of 12 g! A dose of 8 g/day was then confirmed to be safe with a 3-month use. It should be noted, however, that high doses may cause digestive problems such as nausea or diarrhoea, or even headaches in sensitive persons. Moreover, doses in the hundreds of milligrams are usually sufficient to achieve a positive epigenetic effect. Some research also suggests that higher doses may adversely affect sperm motility and should be avoided by men seeking to conceive. (57, 94, 95)

Caution (and ideally consultation with the treating physician) is advisable if you are taking any medication. In some cases, curcumin may increase their effectiveness – this applies to some antibiotics and chemotherapy drugs, for example, which may be desirable. However, in the case of some chemotherapeutic drugs (e.g. cyclophosphamide) and other drugs, it may decrease their effectiveness and thus impair the efficacy of the treatment. Because curcumin reduces blood clotting, it should not be taken with blood-thinning drugs. This is similar to antidiabetic drugs, which on their own lower blood sugar levels and could lead to hypoglycaemia when combined with these drugs. The combination of curcumin with antacids (i.e. drugs that reduce stomach acidity) is also inappropriate (94).

Suitable combinations

Curcumin is most often combined with substances that improve its bioavailability, i.e. piperine or quercetin. At the same time, however, it can also promote the absorption of other epigenetically acting substances such as resveratrol, boswellia or EGCG on its own (64, 67). However, other combinations are also possible.

Inflammation and Pain: curcumin + ginger (75), curcumin + zinc (76), curcumin + quercetin (84), curcumin + boswellia (86), curcumin + coneflower (87)

Diabetes: curcumin + gurmar (69), curcumin + zinc (76), curcumin + quercetin (83)

Cancer: curcumin + indole-3-carbinol (70), curcumin + genistein (71), curcumin + resveratrol (73), curcumin + OPC (74), curcumin + milk thistle (78), curcumin + quercetin (82)

Immunity and antimicrobial action: curcumin + ginger (75), curcumin + zinc (76), curcumin + quercetin (84), curcumin + coneflower (87)

Alzheimer’s and Parkinson’s disease: curcumin + butyrate (68)

Depression: curcumin + butyrate (68)

Cystic fibrosis: curcumin + genistein (72)

Hair fall: curcumin + ginger (75)

Weight loss: curcumin + zinc (76), curcumin + chicory (80), curcumin + quercetin (81)

Arthritis: curcumin + bromelain

Liver: curcumin + milk thistle (77), curcumin + chicory (80), curcumin + bayberry (88)

Sports performance, muscle condition: curcumin + magnesium + vitamin D3 (79)

Autoimmune diseases: curcumin + boswellia (85)

Kidney: curcumin + boswellia (86)

Heart and blood vessels: curcumin + EGCG (89)

Thyroid: curcumin + selenium