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Curcumin & Piperine

Written by Dr. Tom Shurlock for and on behalf of GWF Nutrition Limited.

Copyright: GWF Nutrition Limited - Not for Reproduction.

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Over recent years there has been a rise in the popularity of turmeric, with a wide range of claimed benefits. Many of these benefits are based on observed results and so are qualitative rather than quantified; many are supported by scientific research, but mostly in the realm of human health. It is probable that some effects are transferrable across species but, as most work has been carried out on cancer and liver disease, it is necessary to be selective in substantiating the effects.

Despite this, popular use of turmeric in horses shows a range of “treatments”. An online survey conducted recently found that owners reported to be highly effective for stiffness, mud fever and sarcoids, but had a negative effect on ulcers, sweet itch and hindgut disturbance. Amongst this was a range of other effects, sometimes conflicting (Marlin et al., 2017).

Generally, the use of such products has plenty of anecdotal support but there is hard data available that supports some claims.

Turmeric has been reported to be anti-fungal and antimicrobial as well as larvicidal and nematocidal. It is also anti-inflammatory, anti-mutagenic (anti-cancer), anti-arthritic and an antioxidant. It also reduces platelet aggregation (clotting) and lowers blood glucose. Furthermore, it has been reported as having anti-toxic properties against, for example, cadmium, zearolenone and aflatoxin.

What does transpire from the scientific reports is the breakdown of the active components of turmeric and which ones have which effect.

The turmeric plant contains ~ 6% volatile oil, which contains monoterpenes and sesquiterpenes, including curcumene, zingiberene, a,b and ar-tumerone (the essential oils) and the diarylheptanoid phenolic curcumin. The major essential oils vary between leaf (mainly phellandrene), flower (p-cymen -8-ol) and rhizome (tumerone) and growing conditions. Also, there are colouring agents comprising the curcumoids monodesmethoxycurcumin and bisdemethoxycurcumin. In the main the active curcumin is responsible for most of the functional characteristics, although properties such as anti-arthritic may be a response to the to the other actives.

Curcumin has been reported as having anti-microbial properties, across a wide range of organisms. Phenolics, generally, have antibacterial properties with a range of efficacy against aerobic and aneaerobic pathogens, including staphylococcus, salmonella and E. coli (Balan et al., 2016). Curcumin has a relatively high “kill” compared to phenolics such as coumarin, roesmannic acid and eugenol, but was poorer than thymoquinone and xanthohumol. However, when it came to specific bacteria such as Clostridia species and some Bacillus efficacy was high.

One of the major functions of curcumin is as an anti-inflammatory factor. Inflammation and oxidative stress are uniquely coupled with each other. Tissue injury releases inflammatory mediators, such as pro-inflammatory cytokines, TNF-α and IL-1 from leukocytes, monocytes and macrophages. These cytokines further trigger other pro-inflammatory cytokines. Microbial infection stimulates what is known as a respiratory burst generating oxidative factors. These both can lead to the activation of the transcription nuclear factor NF-κB, which acts as a regulator to all these pro-inflammatory and pro-oxidative factors. Curcumin is reported to inhibit this regulator (Biswas et al., 2008). Microbial infection in the gut stimulating an inflammatory response is governed by the NF-κB and curcumin has been evidenced as having a role in disorders such as IBD (Cho & Park, 2015)

Curcumin also appears to have a down regulating effect directly on the pro-inflammatory cytokines, as well as growth factor receptors and matrix metalloproteinase. In fact, it is reported that curcumin acts as an anti-inflammatory through a wide range of pathways which makes it a central player in interfering with pro-inflammatory signaling pathways.

Moving on to the role of curcumin in combatting oxidation, its action follows several pathways. Curcumin is involved in a increasing the activities of superoxide dismutase, (SOD.), catalase, (CAT), glutathione peroxidase (GPX) and glutathione (GSH), all factors in combatting oxidation (Prabu, 2007). For example, GSH is a regulatory pathway that affects ROS (reactive oxidative species) and NO (nitric oxide) which, in turn, have a degenerative effect on nerve cell linings through lipid peroxidation, thereby affecting neural function (Chang et al., 2014).

Other pathways that curcumin has been shown to have antioxidative effects include mitochondrial dependant NO-ROS pathway that leads to controlled apoptosis – cell death. Curcumin, as a phenolic, is also a primary antioxidant and acts by mopping up free radicals, especially as lipid radicals. As such they themselves are oxidized which may explain the supportive role of ascorbic acid. Curcumin is thought to act through direct action on combatting lipid oxidation (Sonia et al., 2015).

There are many common pathways between oxidative stress, inflammation and imunomodulatory factors. In brief, trauma, damage or microbial invasion triggers the body into a series of responses. First are pro-inflammatory factors that are activated to enclose and shut down the damage. Many of these factors also initiate macrophages (anti-microbial activity), and generate oxidative processes. All these mechanisms are the natural and normal response to trauma which, once the problem has been resolved, convert to anti-inflammatory pathways, allowing dissipation of toxins, negative factors and generative products. However, if the situation is chronic – that is the resolution of the problem becomes compromised – natural anti-inflammatory processes may not kick in and the use of external nutraceuticals are necessary.

Although curcumin is the major active component of turmeric and is responsible for the majority of the spice’s observed effect (some topical effects, such as antifungal and larvicidal activity are down to the tumerones), bioavailability is a major problem. Research has shown that there is rapid disappearance of orally presented curcumin. Ireson et al (2001), in animal trials showed an oral dose of curcumin resulted in a miniscule increase in plasma levels, whilst intravenous presentation was cleared from the plasma within 1 hour. This implies that two mechanisms are involved. Firstly, curcumin is not easily absorbed across the gut wall and, secondly, it is rapidly metabolised.

Although there are two mechanisms, there is confusion, with statements on the role of piperine implying it improves bioavailability through enhancing curcumin absorption. Piperine is a bioactive phenol extracted from two species of pepper plant, including black pepper. It acts as an inhibitor of a process called glucuronidation, which converts some compounds into a water-soluble version before eliminating from the body either through the bile or the urine. Its main sites of action are the liver and the intestine. Curcumin is particularly susceptible to glucuronidation (one of the forms of curcumin is curcumin glucuronide), and research has shown that feeding piperine alongside curcumin (in a ratio of 1:1000) improved serum curcumin by a factor of 20 in humans, although this factor was only 1.5x in rats (Shoba et al., 1998).

There have been advances in improving the absorption of curcumin across the gut lining. Because of the potential for curcumin as an anti-inflammatory component in human conditions such as IBD (Jurenka, 2009) work has been concentrating on digestive bioavailability. Work with curcumin-phospholipid complexes have shown 50-1000x improvement of serum bioavailability (Marczylo et al, 2007); and current advertisements in the papers are promoting a curcumin/lecithin combination, nanoparticles (Kakkar et al., 2011) and a micro-emulsion formula (Cretu et al., 2011). These “routes” can be explained by the Oatinol Delivery System (see Knowledge Base). Curcumin has two forms, one poorly soluble in water, the other in ethanol, so incorporation into hydrophilic/hydrophobic phospholipid, especially as a very fine emulsion, will improve absorbability. Enhanced absorption, coupled with reduced glucuronidation, ensures that curcumin in GWF products (currently the Joint Aids, Digestive Aid and X-Lam Aid) have a positive effect on serum levels and subsequent impact on trauma based processes.

Curcumin influences many processes involved in the support and control of oxidative, inflammatory and immune processes. Whilst, in humans, it may be curcumin’s role in cancer modulation (and this involves complex pathways that have some commonality with those involved in inflammation – tumour necrotic factors - TNF - for example) its impact on chronic inflammation and oxidation demonstrates its use in GWF Nutrition products.


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