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Intestinal alkaline phosphatase - a powerfully protective enzyme

alkaline phosphatase The digestive system is a complex group of organs which continues to reveal new secrets. Research in this area has been growing over the last 20 years, as scientists try to improve their understanding of how it functions. At the end of the 1990s, it was suggested that the stomach contained a ‘second brain’, a term coined by Michael Gershon who first hypothesised the existence of an autonomous nervous system in the digestive system1. The past few years have also been marked by major discoveries relating to gut microbiota – the collection of microorganisms that play a role in neurological, digestive and immune function. Many scientists are thus investigating mechanisms that influence the balance of gut microbiota. And it now seems that a long-known intestinal enzyme plays a key role in maintaining intestinal homeostasis. That’s the conclusion of a number of studies on intestinal alkaline phosphatase, the exact functions of which had until now remained elusive2. Controlling the activity of this enzyme could well prove beneficial in the prevention and treatment of certain diseases.

Intestinal alkaline phosphatase, a specific and little-understood enzyme

Intestinal alkaline phosphatase is one of a large group of alkaline phosphatases. Present in many living organisms, these enzymes exist in the human body in various forms and at various sites, as described in an overview published in theIndian Journal of Clinical Biochemistry 3. According to the authors, there are four distinct isoenzymes within the human alkaline phosphatases. These four enzymes produce the same chemical reaction but have a different chemical structure. They are: intestinal phosphatase alkaline, placental phosphatase alkaline, germ cell phosphatase alkaline and tissue non-specific phosphatase alkaline found in the liver, kidneys and bones. At their individual levels, each of these enzymes catalyses the hydrolysis of phosphoester bonds – in other words, they break the bond between a phosphate and a hydroxyl group of a molecule, via the action of a water molecule. Although the purpose of this chemical reaction has yet to be fully explained, alkaline phosphatases are believed to play key roles. Existing at various essential organ sites within the body, they may be involved in many functions, particularly intestinal alkaline phosphatase, which has been shown to play different roles within the digestive system.

Protective role of intestinal alkaline phosphatase in the digestive system

Recent studies have shed light on some of the mechanisms of action of intestinal alkaline phosphatase. Published in a number of scientific journals such as Nutrition Reviews and World Journal of Gastroenterology2,4, these studies have demonstrated that the enzyme may play a protective role in the digestive system, in particular, participating in the absorption of lipids, regulating intestinal pH and detoxifying the gut. In this way, intestinal alkaline phosphatase may help protect the body against disease from certain pathogens. The mechanism of action responsible is the enzyme’s ability to dephosphorylate certain toxic microbial components. This dephosphorylation inactivates structures such as lipopolysaccharides, free nucleotides and specific proteins of bacteria such as flagellin. Intestinal alkaline phosphatase also helps defend the body by reducing certain inflammatory disorders.

Effect of intestinal alkaline phosphatase in intestinal homeostasis

Alongside its protective role, this key enzyme may also be involved in maintaining homeostasis in gut microbiota. Preserving equilibrium here is particularly important given the proven role of gut flora in the body’s digestion and immune defences. A study on the potential relationship between intestinal alkaline phosphatase and gut flora was published in 2010 in the specialist journal Gut 5. Researchers examined the effect of the enzyme in mice whose gut flora had been compromised by infection with pathogenic bacteria. Following treatment with antibiotics, the mice were supplemented with intestinal alkaline phosphatase. The study produced very encouraging results, with the orally-administered supplements positively affecting the growth of bacteria which makes up gut flora. While additional studies are needed on the potential of intestinal alkaline phosphatase supplements in humans, these results confirm the enzyme’s role in intestinal homeostasis. It may prove to be of particular benefit in maintaining or restoring gut flora balance in the face of external aggressors.

Preventive and therapeutic potential of intestinal alkaline phosphatase

Given the protective effect of intestinal alkaline phosphatase, and its key role in intestinal homeostasis, this enzyme offers huge possibilities in the prevention of digestive and inflammatory disorders. It is also arousing interest among the scientific community for its potential to treat chronic inflammatory diseases. Tests already conducted with patients have produced beneficial effects from supplementation against ulcerative colitis and sepsis, as well as during surgery such as coronary bypass operations4. Additional research and clinical trials are currently underway to confirm the benefits of intestinal alkaline phosphatase. These preliminary results open up a host of preventive or curative possibilities for supplementation with this enzyme.

Potential correlation between intestinal alkaline phosphatase and type 2 diabetes

In addition to its therapeutic potential in chronic inflammatory disease, intestinal alkaline phosphatase may offer benefits in preventing certain metabolic disorders. So concluded a recent study published in the journal EBioMedecine which demonstrated a correlation between levels of the enzyme and type 2 diabetes6. The study’s authors based their research on previous findings that showed mice with type 2 diabetes had low levels of intestinal alkaline phosphatase. To confirm this analysis, the researchers assessed levels of the enzyme in 202 diabetic patients and 445 healthy controls. Tests revealed the former to have 50% less intestinal alkaline phosphatase than the non-diabetic subjects, suggesting that a lack of this enzyme could be associated with the development of certain metabolic syndrome problems. Additional studies are needed to explore the potential of supplementation with intestinal alkaline phosphatase in preventing metabolic disorders.

Intestinal alkaline phophatase, a diet-sensitive enzyme

While scientists’ understanding of this enzyme’s functions is growing, they have also noted it is sometimes present in the body in a modified state. This change is primarily due to elements in our diet, such as L-phenylalanine, a compound which, according to the results of a study published in Biochemical Journal7, may inhibit intestinal alkaline phosphatase.Though essential for certain of the body’s functions, L-phenylalanine at high levels may be harmful because it blocks the beneficial effects of intestinal alkaline phosphatase. Unlike L-phenylalanine, other dietary components may moderate the enzyme’s effects8. This may be the case for certain lipids, carbohydrates and proteins and studies are in progress to improve our understanding of the effects of diet on intestinal alkaline phosphatase.

Should we be increasing our levels of intestinal alkaline phosphatase?

Preliminary findings suggest that supplementing with this enzyme may be beneficial in preventing or treating a number of diseases. Some compounds may also offer advantages in increasing levels of intestinal alkaline phosphatase. This echoes similar results obtained with other alkaline phosphatases, particularly those present in the liver and bones. Dietary supplements have been shown to be effective in maintaining or restoring levels of alkaline phosphatase. This is particularly so for Robuvit®, an extract of French oak wood, which has demonstrated positive results in normalising alkaline phosphatase levels in the liver9, 10

Importance of gut microbiota cannot be stressed enough

In the many studies conducted on intestinal alkaline phosphatase, scientists also remind us of the importance of maintaining equilibrium in gut microbiota. While supplementation with this intestinal enzyme may prove to be beneficial, other solutions for maintaining or restoring gut microbiota are already available. Probiotics, for example, are microorganisms which, when ingested in sufficient quantities, offer significant health benefits. They are primarily known for their positive effect in the intestines as described in our article Is there a ticking time-bomb in your gut?». Probiotics are available in a range of formulations to help you take advantage of their health benefits.

Sources :
1. Gershon M. « The Second Brain: A Groundbreaking New Understanding of Nervous Disorders of the Stomach and Intestine », Harper Paperbacks, 1999.
2. Lallès JP, « Intestinal alkaline phosphatase: novel functions and protective effects », Nutr Rev, 2014 Feb, 72(2) : 82-94.
3. Sharma U, Pal D, Prasad R, « Alkaline phosphatase: an overview », Indian J Clin Biochem, 2014 Jul, 29(3) : 269-78.
4. Estaki M, DeCoffe D, Gibson DL, « Interplay between intestinal alkaline phosphatase, diet, gut microbes and immunity », World J Gastroenterol, 2014 Nov 14, 20(42) : 15650-6.
5. Malo MS, Alam SN, Mostafa G, Zeller SJ, Johnson PV, Mohammad N, Chen KT, Moss AK, Ramasamy S, Faruqui A, Hodin S, Malo PS, Ebrahimi F, Biswas B, Narisawa S, Millán JL, Warren HS, Kaplan JB, Kitts CL, Hohmann EL, Hodin RA, « Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota », Gut, 2010 Nov, 59(11) : 1476-84.
6. Malo MS, « A High Level of Intestinal Alkaline Phosphatase Is Protective Against Type 2 Diabetes Mellitus Irrespective of Obesity », EBioMedicine, 2015 Dec 1, 2(12) : 2016-23.
7. H N Fernley, P G Walker, « Inhibition of alkaline phosphatase by L-phenylalanine », Biochem J, 1970 Feb, 116(3) : 543–544.
8. Lallès JP, « Intestinal alkaline phosphatase: multiple biological roles in maintenance of intestinal homeostasis and modulation by diet », Nutr Rev, 2010 Jun, 68(6) : 323-32.
9. Belcaro G, Gizzi G, Hu S, Dugall M, Pellegrini L, Cornelli U, Cesarone MR, Trignani M, Maione C, « Robuvit® (French oak wood extract) in the management of functional, temporary hepatic damage. A registry, pilot study. », Minerva Med, 2014 Feb, 105(1):41-50.
10. Pellegrini L, Belcaro G, Dugall M, Corsi M, Luzzi R, Hosoi M, « Supplementary management of functional, temporary alcoholic hepatic damage with Robuvit® (French oak wood extract). », Minerva Gastroenterol Dietol, 2016 Mar 3.
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