Digestion, absorption and metabolism of Turmeric

Adapted from an article published on another site, used with permission

You wouldn’t think you needed to be a nutritionist or food scientist to use turmeric effectively in your diet, would you! If you lived where the traditional cuisines of Asia are eaten, where turmeric plays such a large part, you might not need to know any more about turmeric than your parents taught you. Turmeric would be just another one of the spices in your regular diet.

Unfortunately, that’s not the case for most of us. Given the huge amount of misinformation about turmeric that circulates on the internet, it might be helpful to set out some of the things that affect turmeric’s digestion, metabolism and absorption.

One of the biggest problems with Digestion, Metabolism and Absorption is that these three terms are often confused with each other. They are distinct and separate processes, but many internet authors use the terms interchangeably or mix up their purposes. The fact that they may take place at the same time at different points in the body can make the picture even more confusing.

Digestion is the series of steps that break down foodstuffs into their component parts. Foods are composed of starches (carbohydrates), proteins, fats, and a long list of vitamins, minerals and other things, all stuck together with various mechanical, electrical and chemical bonds. Digestion breaks down those bonds, separating the constituents into individual components (or at least smaller combinations of things). Absorption is the process of moving nutrients from the intestines into the bloodstream. Most nutrients are absorbed through the lining of the small intestine, but water-soluble nutrients are absorbed differently from fats and fat-soluble compounds. Metabolism converts nutrients into forms that can be used (or stored in the body), and also into forms that are removed (excreted) from the body. The technical word for the latter is xenobiotics. Sometimes you may see them referred to as xenotoxins. The use of ‘toxin’ does not mean that these things are poisons, only that they do not inherently occur within the body, and they are not accumulated in the body. The desirable ones have a part to play, but are removed when that role is accomplished. In fact, many of the vitamins and minerals that are important components of our foods are xenobiotics that are metabolized and removed within a specified time frame for each one.

The sequence of absorption and metabolism is not the same for all foods, nor for medications. Some are metabolized only in the liver, a few in the kidneys, and some things are not metabolized at all. For some, metabolism begins in the small intestine before the food or drug ever reaches the bloodstream. Metabolism is frequently a multi-step process, with one phase taking place in the small intestine and the final step in the liver and other tissues. Regardless of the specifics for any particular food or drug, the end result is to prepare it for use and possible storage in the body, and in the case of xenobiotics, to facilitate its elimination when it has completed its purpose.

Food has to be broken down for several reasons. First, most foods contain different compounds that can't all be absorbed through the same pathways. So they have to be divided up into smaller units of similar composition. Second, the molecules in our foods are too large to be absorbed without being separated into smaller pieces. And finally, different processes are needed to turn different kinds of nutrients into energy for our bodies. For example, a spice may contain fats, starches and proteins. They can't all be used in the body by the same processes. So they must be broken down into individual compounds which are then combined with other like things. Digestion takes care of all these needs.

Most people think of digestion as something that happens only in the gut, but it actually begins in the mouth with a change in your saliva. When you smell food, and even when your brain knows a regular meal time is approaching, serous glands in your mouth and on the surface of your tongue secrete alpha-amylase, an enzyme that begins the process of breaking down fats and starches. Amylase digests starches into maltose and dextrin, two simpler starches. The serous glands also secrete lingual lipase, which begins the digestion of medium and long-chain triglycerides (types of fat).

If your parents told you to chew your food properly (do parents say that any more?), the reason is that it gives your digestive system a head start on breaking down the food before it ever gets to your stomach.

Once in the stomach, the food is subjected to acids, various gastric lipases and mechanical churning to continue breaking it down. The upper part of the stomach (the fundus) mixes the food with gastric lipases, pepsin and gastric acids. These continue the process of breaking down fats and proteins begun in the mouth. This is not digestion in the sense of making nutrients directly available for absorption, but it does break down larger complex molecules (especially the proteins) into smaller units that the small intestine will digest further.

The lower part of the stomach (the antrum) contracts rhythmically to mechanically break down the contents, and churn them into the half-digested mixture called “chyme.” Because the sections of the stomach are not physically separate from each other, the contents are exposed repeatedly to gastric juices and enzymes as stomach contractions move the food around.

Chyme passes into the small intestine at a rate closely controlled by the nervous system. This is essential, to keep the alkaline environment of the small intestine from being overloaded with the acidic contents of the stomach. Secretin, a peptide produced by the duodenum (the first part of the small intestine), stimulates the pancreas to release fluids rich in sodium bicarbonate. This raises the pH of the chyme to the optimum pH for pancreatic enzymes and bile to complete the task of digesting the food.

At the end of these processes, the compounds that started out as fats, proteins and carbohydrates are reduced to monoglycerides, amino acids and monosaccharides. Please note that this is a very simplified explanation, but I was afraid that trying to add more details would put people off from reading it. It isn’t meant to be a treatise on any of the topics, just an overview of the differences between digestion, absorption and metabolism.

Curcumin is not digested (though it may be broken down into what’s called “degradation products” – more on that later): it’s one of the compounds that becomes available when the starches in turmeric are digested. Phenols (curcumin is a polyphenol) are bound into the cell walls of plants, and when those of turmeric are broken down, curcumin is one of the compounds that’s released.

Up to this point, although water-soluble and fat-soluble nutrients are acted upon differently, they are still all together in the digestive tract. Now, however, the pathways for water-soluble and fat-soluble nutrients diverge.

The small intestine is where the bulk of nutrient absorption takes place. Like the stomach, it has distinct sections. The one closest to the stomach is called the duodenum and the one closest to the large intestine is the ileum. In between are all the winding loops of the jejunum. This image gives an idea of how the small intestine is situated in the abdominal cavity.

The jejunum is lined with a layer of special cells called 'enterocytes,' present on the surface of columnar forms called villi. These have an unusual feature. The outside of each enterocyte is covered with additional tiny projections called microvilli, so tiny that they can be seen individually only with an electron microscope. With an optical microscope, they look like a fuzzy layer on the outside of the enterocytes. If you come across a reference to the 'brush border,' of the intestine, it is these microvilli that it refers to, and the term 'brush border' came about because of the fuzzy appearance. Their presence hugely increases the surface area available for nutrient absorption.

Each of the villi has a capillary running up and down inside it, along with a tube (called a lacteal) that connects with the lymph system. The monosaccharides and other water-soluble products of digestion are absorbed through the enterocytes on each villus and diffuse into the capillary inside. From there, they go to the hepatic portal vein and to the rest of the bloodstream.

The long-chain fats (all but a few oils like coconut oil and palm oil) are repackaged within the enterocytes into packets called chylomicrons. These move from the enterocytes into the lacteals, where they enter the lymph system and ultimately the bloodstream.

Short- and medium-chain fats, however, go straight into the bloodstream via the portal vein, along with the monosaccharides and peptides. The red and blue colors of the capillary sections in Figure 3 above indicate that each villus has an incoming blood supply from the arteries and an outgoing blood vessel leading to a vein (in this case, the portal vein).

The term “portal vein” gets tossed around a lot without much explanation of what it actually is. Unlike the other veins in the body, it does not go to the heart. It travels only from the small intestine to the liver, a distance of about 3 inches in the average adult.

Direct absorption into the portal vein has been cited as one reason to prefer coconut oil over long-chain oils such as olive oil and most others. Some have even promoted the use of MCT oils (extracts of medium chain triglycerides from coconut oil). Yet this has mixed benefits. Anything that is packaged with the coconut oil (such as the curcumin from turmeric, for example) undergoes hepatic metabolism before reaching the primary bloodstream circulation. On the other hand, olive and other long-chain oils take longer to enter bloodstream circulation, as they must detour through the lymph system. But they do not undergo hepatic metabolism immediately, so the amount of free curcumin available to tissues is greater, at least until the curcumin reaches the liver.

Unrefined coconut oil is approximately 50% medium and short-chain fatty acids with the balance being long-chain fatty acids. It may be reasonable to assume that about half of any fat-soluble nutrients would be carried by those lipids directly into circulation via the portal vein, and about half would be packaged with the long-chain fatty acids and arrive later via the lymph system. This is a very general assumption, though, and would vary widely depending on individual physiology and with the mix of foods in any given meal. It isn’t meant to stipulate any specific percentages: it just provides an overall picture of the two different routes via which fat-soluble nutrients may enter the bloodstream.

The first metabolic transformation takes place in the small intestine, before curcumin ever enters the bloodstream. The curcumin molecule is relatively stable in the acid environment of the stomach. But as mentioned above, the pH of the small intestine is much higher. Some of the curcumin undergoes autoxidation, a reaction that results in multiple ‘degradation products,’ such as vanillin, furaldehyde and ferullic acid. These all have some anti-inflammatory and antioxidant properties as well, and their presence may account for the very wide range of benefit attributed to curcumin.

Curcumin is also affect by other metabolic processes. The enterocytes mentioned above express enzymes of the cytochrome P450 family, primarily the CYP3A sub-family. Curcumin is a substrate for CYP3A4 activity, via a compound called Nicotinamide Adenine Dinucleotide Phosphate, or NADP+ (the reduced form, called NADPH, is the one that actually participates in these reactions). If this is getting unnecessarily complicated, feel free to skip the details. The significant point is that much of the curcuminoid content in turmeric is converted into another form in the small intestine. Obviously it would be desirable to prevent this, or at least to slow it down. That’s where the piperine in black pepper enters the picture. It inhibits the synthesis of CYP3A4 in both the enterocytes and in the liver, and allows curcumin and the other two curcuminoids to remain in their original state for a longer period of time. Because more curcumin is available over a longer interval, more of it can be absorbed into the lymph system if a fat is present. And if a medium chain fatty acid is present, more of it can go straight to the liver via the portal vein, and thence into general circulation.

This is not the final step for curcumin, however. This is what’s often referred to as Phase 1metabolism. Phase 1 metabolism takes place in the small intestine before curcumin and the other curcuminoids reach the bloodstream.

CYP3A4 also plays a part in the further metabolism of curcumin, via its effect on glucuronidation. CYP3A4 increases the activity of another enzyme, UDP-glucuronosyltransferase (UGT-1A). Therefore, inhibition of CYP3A4 will also inhibit the activity of UGT1A. So CYP3A4 affects Phase 2 metabolism as well, which takes place in the liver itself. Curcumin is also metabolized to curcumin sulfate, and these metabolites—curcumin sulfate and curcumin glucuronide—are the two found in greatest amounts in plasma, both in humans and in laboratory animals. These are the forms in which curcumin is finally excreted in the urine.

This is just an overview of how turmeric is digested and its primary active constituents—the curcuminoids—are absorbed and metabolized. If you’re interested in more detail, PubMed has many articles on the subject. But these are the basic processes that affect how turmeric is used in the body.