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Turmeric Extract
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There’s so much information, misinformation, and so many differing viewpoints (with justification) out there about Curcumin that you can spend a lifetime researching it on the Internet and never really come to any conclusion. There are over 3,000 scientific research projects happening around the world looking at the therapeutic effects of this amazing natural substance. There are also a large number of people who question whether it has any benefits at all.

Apart from a desire to tell my story, I feel compelled to talk about my own experiments with Curcumin, Prostate Cancer and how it has benefitted me – anecdotal evidence, but it’s there nonetheless. But I also need to share with you a lot of what I’ve learned along the way, and this is a good place to start.

What is Curcumin?

‘Curcumin’ is a catch-all name for a naturally-occurring substance found in the spice Turmeric. It’s been in use by humans for thousands of years as a spice, medicine, cosmetic and dye. In Ayurvedic medicine, it’s used for a variety of ailments – from antiseptic paste for wounds and infections to skin maladies and intestinal disorders.

The ‘active’ ingredient in Turmeric is primarily ‘Curcumin’ – approximately 5% by volume – divided into three ‘curcuminoids’:
Curcumin (also known as diferuloylmethane, ‘CUR’, Curcumin I or Curcumin 1) – 77%
Demethoxycurcumin (also known as ‘DMC’, Curcumin II or Curcumin 2) – 17%
Bisdemethoxycurcumin (also known as ‘BDMC’, Curcumin III or Curcumin 3) – 6%
Most commercially available Curcumin powder is a mixture of all three in the rough percentages shown.

You can see it’s confusing – ‘Curcumin’ is often used to refer to all three curcuminoids, but often just to refer to diferuloylmethane. They are all very similar, but increasingly arguments rage over the efficacy of each of the three curcuminoids. You may read much on the Internet that says only CUR is efficacious. This is by no means agreed by all researchers into all ailments, and there are many good reasons why DMC and BDMC are of equal or potentially greater interest.

What are Curcumin’s therapeutic properties?

It’s a well known antioxidant and anti-inflammatory, with antimicrobial and anticarcinogenic properties. The mechanisms by which it operates are the subject of intense research, but here for example is a tidbit about its anti-inflammatory properties:

“Research shows Curcumin is a highly pleiotropic molecule capable of interacting with numerous molecular targets involved in inflammation. Curcumin modulates the inflammatory response by down-regulating the activity of cyclooxygenase-2 (COX-2), lipoxygenase, and inducible nitric oxide synthase (iNOS) en:2ymes; inhibits the production of the inflammatory cytokines tumor necrosis factor-alpha (TNF-a), interleukin (IL) -1, -2, -6, -8, and -12, monocyte chemoattractant protein (MCP), and migration inhibitory protein; and down-regulates mitogen-activated and Janus kinases.”
(From “Anti-Inflammatory Properties of Curcumin, a major constituent of Curcuma longa: a Review of the Preclinical and Clinical Research”, Julie S. Jurenka, MT(ASCP))

As you can see this is really technical and this is the main reason you can’t hope to understand all this in scientific terms! So you’ll need to take a small leap of faith and accept any number of scientific papers which confirm the properties of Curcumin. I think this summary is a good one:

“Curcumin is a highly pleiotropic molecule that was first shown to exhibit antibacterial activity in 1949. SInce then, this polyphenol has been shown to possess anti-inflammatory, hypoglycemic, antioxidant, wound-healing, and antimicrobial activities.Extensive preclinical studies over the past three decades have indicated curcumin’s therapeutic potential against a wide range of human diseases. In additiona, curcumin has been shown to directly interact with numerous signalling molecules. These preclinical studies have formed a solid base for evaluating curcumin’s efficacy in clinical trials.”
(From “Therapeutic Roles of Curcumin: Lessons learned from Clinical Trials”, Gupta, Patchva and Aggarwal, 2013)

This paper is an awesome one, from the AAPS Journal. There is a table entitled “Human Diseases against which Curcumin has exhibited activity” which I have summarised in CurcuminJournal’s guide to the diseases where curcumin shows therapeutic potential. Take a look. I was flabbergasted.

Why is Curcumin not already as common a natural treatment as aspirin?

This is another of those million dollar questions – in fact, ‘dollars’ most certainly come into it. Research into Curcumin really appears to be driven by two factors – first and foremost, genuine academic interest in its efficacy. And secondly, companies that make curcumin and curcumin supplements.

Interestingly, it’s been pointed out to me that the major pharmaceutical companies that fund so much research have a vested interest in ignoring curcumin. It’s a naturally occurring substance. Curcumin costs less than $200 a kilogram. It’s not going to enrich their shareholders like a complex, expensive drug.

It is beginning to catch up now – every month that passes, more is discovered about curcumin. And that can only be good, even if it’s research poking holes in its efficacy! We need to know as much as possible.

Whatever you learn about Curcumin, and whatever you think about its use as a therapeutic, NOTHING matters more than the question of bioavailability.

What does that mean? Well, this:

“The reasons for reduced bioavailability of any agent within the body are low intrinsic activity, poor absorption, high rate of metabolism, inactivity of metabolic products and/or rapid elimination and clearance from the body. Studies to date have suggested a strong intrinsic activity and, hence, efficacy of curcumin as a therapeutic agent for various ailments.
“However, studies over the past three decades related to absorption, distribution, metabolism and excretion of curcumin have revealed poor absorption and rapid metabolism of curcumin that severely curtails its bioavailability.”From “Bioavailability of Curcumin: Problems and Promises”, Anand, Kunnumakkara, Newman, and Aggarwal, MOLECULAR PHARMACEUTICS VOL. 4, NO. 6

That’s pretty much the problem in a nutshell, and why many websites dedicated to cancer therapies flatly reject Curcumin does anything except stain your fingers – especially when written up to the mid 2000s. Because even ingesting huge amounts of curcumin powder (up to 12 grams) every day only yielded nanograms of curcuminoids in your bloodstream, far less than research suggests will have any real therapeutic effect on an active cancer.

(That said, there are many scientists who believe that a diet high in turmeric eaten in meals with a significant fat content contribute to the lower rates of cancer in the Asian continent. It may have a preventative benefit in lower doses. Check this out in CurcuminJournal’s Guide to Cancer rates in USA vs India.)

Curcumin powder has poor solubility in water, and also degrades quickly in the neutral pH ranges of your intestine. It’s poorly absorbed in the gut, with most of it simply ending up in our faeces, and what is absorbed is quickly metabolised in the liver or excreted via the kidneys, ending up in our urine. All in all, poor bioavailability and a short timespan in our blood plasma; not very therapeutically beneficial.

There have been many leaps forward in improving Curcumin bioavailability over the last five years. There are many different approaches that have been taken, and if you read most of the stuff Curcumin supplement manufacturers peddle, you’d think that there is only one true way – their way or the highway! It’s pretty easy to poke holes in any of the claims made to be honest, but there is also no doubt that there are advances being made in Curcumin delivery.

These are the main areas that have shown interesting results. I really suggest getting stuck into some of the research papers out there, although frustratingly some of the best and more recent are not publicly available.

Curcumin complexed with phospholipids improves bioavailability
Picture
I’ve been lucky enough to have this explained to me by a biochemist, and I’m still struggling to understand the chemistry behind it!

You can skip the explanation if you like – it explains why Curcumin complexed with a phospholipid is more readily absorbed into the body and can also be transported more effectively into cells.

You don’t have to know why unless you want to, but it does also help in identifying the different kinds of Curcumin supplements and why they may work better than others.

Here goes.

Curcumin is a highly lipophilic substance, ie fat loving and water hating, so it is insoluble in the water found in your body. If you can somehow attach it to a substance that will make it more easily dispersible in water, then this will massively increase its absorption. This is where phospholipids come in.

Basically, The ‘head’ of a phospholipid is hydrophilic (attracted to water), while the hydrophobic ‘tails’ are repelled by water and are forced to clump together. This water-loving / hating structure means that phospholipids tend to create predictable structures, especially in the presence of water. The diagram above shows what’s known as a lipid bilayer, where the water-loving heads face outwards and the water-hating tails clump together. In fact, cell walls are basically lipid bilayers – our body is made up of them.

Now we get to the point. Curcumin molecules bind strongly to a class of phospholipids called phosphatidylcholine; in the presence of water the phosphatidylcholine will naturally squirrel away the curcumin within bilayers of whatever structure.
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In other words, you can basically disperse curcumin in water if it’s attached to the phosphatidylcholine. In the presence of water, the phosphatidylcholine with curcumin attached to the head group will simply form a structure like those shown in the image, keeping its head to the water and its tails away, and therefore happily dispersible in water.

Additionally, the phosphatidylcholine heads can fuse with other bilayers such as the cell membrane, thus delivering the Curcumin contents more readily into the body’s cells. Now you’re talking double whammy – dispersible in water and hence better absorbed in the gut on the way in, and better absorption into cells once inside.

Where do phosphatidylcholines come from?

Lecithin is a form of phosphatidylcholine (usually made from soy bean), and there are also many marine forms – from mussels for example and also krill oil, both of which have been used by BioMer for its Curcumin supplements which I have been taking.

Clinical trials have shown a Curcumin supplement that uses phospholipids for delivery was 29 times as effective as raw curcumin powder. The supplement used in the tests was Meriva from Indena which uses curcumin powder made up of the three curcuminoids in their usual proportions (see CurcuminJournal’s Guide to Curcumin).

“The relative absorption of a standardized curcuminoid mixture and its corresponding lecithin formulation (Meriva) was investigated in a randomized, double-blind, crossover human study. Clinically validated dosages were used for both products, and plasma levels of all three major curcuminoids [curcumin (1a), demethoxycurcumin (1b), and bisdemethoxycurcumin (1c)] were evaluated. Total curcuminoid absorption was about 29-fold higher for Meriva than for its corresponding unformulated curcuminoid mixture, but only phase-2 metabolites could be detected, and plasma concentrations were still significantly lower than those required for the inhibition of most anti-inflammatory targets of curcumin. Remarkably, phospholipid formulation increased the absorption of demethoxylated curcuminoids much more than that of curcumin (1a), with significant differences in plasma curcuminoid profile between Meriva and its corresponding unformulated curcuminoid mixture. Thus, the major plasma curcuminoid after administration of Meriva was not curcumin (1a), but demethoxycurcumin (1b), a more potent analogue in many in vitro anti-inflammatory assays. The improved absorption, and possibly also a better plasma curcuminoid profile, might underlie the clinical efficacy of Meriva at doses significantly lower than unformulated curcuminoid mixtures.”
From “Comparative Absorption of a Standardized Curcuminoid Mixture and Its Lecithin Formulation”, Cuomo, Appendino, Dern, Schneider, McKinnon, Brown, Togni, and Dixon, J. Nat. Prod. 2011, 74, 664–669

So why am I not taking Meriva, given it’s been tested like this and shown to be effective?

Well, the key is in this same research document – despite the fact that the curcuminoid demethoxycurcumin (Curcumin II or DMC) is only around 17% of the curcumin content of Meriva, it was absorbed in greater quantities than Curcumin I (diferuloylmethane or CUR) which is around 77% by weight.

It stands to reason that a Curcumin supplement that uses just demethoxycurcumin (DMC), weight for weight, will be much more bioavailable than one which uses all three curcuminoids in the same proportion as used in curcumin powder.

In fact the research into Meriva showed that while it had an overall improvement of 29 fold over raw curcumin powder in terms of absorption into the body, if you looked at just the methoxylated ingredients (demethoxycurcumin (Curcumin II) being the larger of the two), it was 50 – 60 fold improved.

BioMer’s Curcumin supplements use only demethoxycurcumin (Curcumin II). By my reckoning, that makes them deliver twice the bioavailability than the equivalent dosage of Meriva, provided you believe that DMC is as effective alone as all three curcuminoids combined. There is much research to support this (especially in the case of cancers as opposed to neurodegenerative diseases) but you can make your own mind up. I made my mind up a while ago and chose the DMC route.

The other main reason I favour the BioMer product over Meriva is that it benefits from the fact that marine Omega 3 fatty acids attach to the phosphatidylcholine tails – not only are the Omega-3s good for you anyway, but there is research that shows that the anti-inflammatory effects of Curcumin and Omega-3s are enhanced when taken together. This is a bit techie, but just skip the bits you can’t understand and you’ll get the gist:

“Inflammatory response plays an important role not only in the normal physiology but also in the pathology such as cancers. As chronic inflammations are associated with malignancies, it is important to prevent inflammation-mediated neoplastic formation, promotion and/or progression. One possible intervention will be using cancer chemopreventive agents such as curcumin (CUR), a potent antiinflammatory
and anti-oxidative stress compound. Polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) are potent anti-inflammatory agents by decreasing the production of inflammatory eicosanoids, cytokines, and reactive oxygen species (ROS).
The present study aims at examining whether CUR with DHA or EPA would have synergistic antiinflammatory
effects in RAW 264.7 cells… Non-toxic concentrations of single and combination of the compounds were investigated at 6, 12 and 24 h. The nitric oxide (NO) suppression effects were most prominent at 24 h. All the combinations of CUR and DHA or EPA with lower concentrations of CUR 5 mM
and 25 mM of DHA or EPA were found to have synergistic effects in suppressing LPS-stimulated NO and endogenous NO levels. Importantly, very low doses of CUR 2.5 mM and DHA or EPA of 0.78 mM could synergistically suppress the LPS-induced prostaglandin E2 (PGE2). The combinations were also found to suppress iNOS, COX-2, 5-lipoxygenase (5-LOX) and cPLA2 but induce HO-1. Taken together, the present study clearly shows the synergistic anti-inflammatory as well as anti-oxidative stress effects of CUR and PUFA.
“From “Synergistic anti-inflammatory effects of low doses of curcumin in combination with polyunsaturated fatty acids: Docosahexaenoic acid or eicosapentaenoic acid”, Saw, Huang and Kong, Biochemical Pharmacology 79 (2010) 421–430

Turning this into plain English – Curcumin taken with Omega-3 acids DHA and EPA had a greater effect on mouse leukemia cells (RAW 264.7) than either curcumin or Omega-3 acids alone.

Also, check out my post about research into the combination of Curcumin and Omega-3 fatty acids on Pancreatic Cancer in CurcuminJournal’s Guide to Curcumin and other cancers. The graph is jaw-dropping. I will be continuing to take my curcumin in a prep like those from BioMer with marine phosphatidylcholine, needless to say.

Curcumin when taken with other substances can increase its bioavailability

They call it adjuvant therapy – by taking something else alongside the Curcumin, you can potentially increase its bioavailability by a variety of mechanics, most of which are to do with reducing the speed of its breakdown, and hence making it more likely to reach and stay in the blood plasma.

It’s been known for some time that Piperine, a natural constituent of black pepper, has many what are known as ‘pharmacokinetic effects’. The chemistry is again very complex, but basically there was a famous pilot study in 1998 that showed piperine could increase the bioavailability of Curcumin 20-fold. This study has been vilified by many, mainly I think because no one has bothered to follow it up with a larger sample.

“The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.”From “Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers”, Shoba, Joy, Joseph, Majeed, Rajendran, Srinivas, Planta Med. 1998 May;64(4):353-6.

OK, the samples were small, but I am sick of reading debunking of this piece of pioneering research from 16 years ago. It’s mostly because it’s used by curcumin supplement manufacturers to justify their use of piperine, or by other manufacturers to show that piperine is not a valid adjunct to curcumin. Search piperine and curcumin in the NCBI research database (not just Google, you get some real Google ranking supplement manipulators up there on this search!) and you find lots of recent research – just click here in fact… So yes, be questioning, but don’t write it off like some ill-informed folks have done historically and continue to do despite new findings.

However, you should absolutely check with your physician about piperine in larger doses – while Curcumin is a very safe substance to take, piperine can not only enhance curcumin bioavailability, but also it can have effects on other drugs you may be taking. This again has been overstated I think, and recent research has showed it has less effect than previously thought, but I recommend reading carefully about this and let your consultant know.

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