Urine Therapy

Urinetherapy is a technique which consists in the ingestion of Urine or its application on the skin through compresses, rubbing or immersion baths. Even though a large number of westerners, who are used to modern medicine might resist this thesis, it is important to note that it is a very ancient practice with proven efficiency as documented in many civilizations through time. It was used in India, Tibet,Egypt, Ancient Greece and the Inca, Maya as well as the Aztec people. There is evidence not so long ago of its use among precursors of modern western medicine. In 1841 Dr. Dioscorides published in England the book "The English Treasure" in which he prescribed Urine to cleanse wounds. In the eighteenth century, dentists in Paris used Urine to clean teeth. During the Middle Ages it was common in Europe to drink one´s own urine as protection against the plagues. Even today, people from Nicaragua to Arabia, to Alaska use Urine to heal physical ailments. Even in the Northeast of Brazil and in other regions where there is a lacking of medical resources, popular tradition recommends the application of children´s urine for ailments of the skin, like rashes and burns from animal poisons like that of tarantulas and jelly-fish.

Despite its historical use and worldwide reach, Urine therapy began to disappear the more science and technology developed. This phenomenon might also be explained by to great pressures exerted from the pharmaceutical Industry on doctors and pure scientific researchers. Since then, natural treatments have in many cases ended up being considered supersticious and have been rarely included in the study programs at medical schools.

This traditional therapy should not be ignored any more. Granted that it might be of use in extreme cases, but there are already people (and there shall be more coming) who find themselves in accute situations with suffering of the physical and mental sort and have no access to traditional treatments, most often for lack of financial resources. In those cases, pure necessity shall warrant the use of this treatment.

In addition, drinking urine means for many people breaking age old barriers of conditioned thinking. If only more people split from the prevailing collective consciousness and took the step to try it. That act in itself could mean tremendous healing.

Reencounter With Urine Therapy

The critical situation of human health, the lack of material resources and the difficulties presented to western medicine in dealing with the numerous problems presented to it, create ongoing pressures in the world population today to try and find simpler, cheaper and more effective forms of treatment.

It is known that in the world today there exist more than twelve thousand alopathic remedies, and that large number is not even close to helping solve the problem of a world health that keeps getting worse and worse.

In addition, the abussive use of artificial medications weaken the body in general and can end up reducing its immunological capabilities, conditions which, at the same time require the use of stronger and stronger treatments. The number of diseases which are out of control keep growing, as well as those for which science has no explanation. Furthermore, urban life keeps polluting the human body, many times with chemical derivatives that are difficult to eliminate.

Within this context, we go back to the notion that the body itself is a great manufacturer of medications, a wonderful laboratory for producing analgesics, antibiotics, substances that rearrange the immune system and even certain hormones that can prevent and cure illnesses.

Urine, as we shall see, is a natural medication which our intelligent biological laboratory produces. It is also an element capable of balancing and stimulating vital body functions such as elimination and defense allowing it to recover its lost vitality.

What is Urine?

Urine is formed in the kidneys by means of an elaborate blood filtration process. Before it is filtered by the kidneys blood passes through the liver where toxins are extracted and discarded by means of the bile through the large instestine. The function of the kidneys involves maintaining the balance of certain substances in the blood as well as controlling the levels of water in the body. This differs from the common held perception that the function of the kidneys is that of eliminating toxins. That function then belongs mainly to the liver. Urine therefore is purely a byproduct of the blood and not an accumulation of toxins. It is not a waste product like feces is.

In the urinary tracts, 99% of the liquid filtered by the kidneys is reabsorved and sent back to circulate in the blood, so only 1% of these filtered fluids, comprising approximately one and a half liters is sent out by the kidneys,stored in the bladder and expelled as urine.

Despite the dependence of its chemical composition in the person diet we could say that in general urine is composed 96% of water and 4% of organic and inorganic elements. Among which there are:

  1. Inorganic Components: sodium chlorate and other chlorine based salts, sulfur based salts,phosphorus,sodium,potassium, calcium,magnessium, copper,fluor, iodine, iron,zinc,phosphoric acid and sulfuric acid.
  2. Organic Components: urea, creatinin, amonia, uric acid, albumin and other proteins apart from 21 species of aminoacids, aminos and organic acids.
  3. Carbohydrates: cetoacids, lactic acids and uric acids.
  4. Vitamins: A, B, C, E omong others and pantothenic acid.
  5. Hormones: hypophysis originated, sexual, prostaglandines, ADH (anti-diuretic hormonium), amon others.
  6. There are Many Substances Which are Currently Being Used in Medications Which are Urine-Based: allantoin, which helps in the cicatrization of wounds and its an ideal anti-wrinkle element; globulins, specially immunoglobulins, which are anti-bodies; urea, responsible for the anti-bacterial capabilities of urine and for its inhibiting capacity against the bacillus of tuberculosis; urochinase, which helps in the dilation of blocked vessels that prevents thrombosis; el 3-metiglioxal that destroys cancer cells.

When the body is intoxicated, the kidneys are not able to work efficiently and allow certain necessary substance to go unused. When the practice of Urine Therapy is started, these vital elements are replaced. Drinking one´s own urine therefore is not the risky proposition that many people consider it to be. On the contrary, urine therapy can be used with no risk, even in the presence of urinary infection.

Urine is not toxic. That is a misleading evaluation done in western societies which lost contact with the wisdom of nature.

The 'Toxins' of the Urine?

Basically there are two groups of substances that are called ' toxins'.

First o all there are the products of the metabolism of the nitrogen in our body, principally uréia, ammonia, úric acid and creatinina; substances, when in excess in the blood, are toxic. Those substances, nitrogenadas nonprotéicas,when taken, are recycled through the help of the intestinal microflora,permitting the nitrogen, before inaccessible to our metabolism,to a synthesis of new proteins. (See the article " Urine therapy: a physiologic " practice). Actually, what happens is that this new nitrogen seems to be, in it´s largest part, used in the endogenous synthesis of amino acids imunonutrients, which would explain a good part of the success of that therapy. (see article " Studies on Urinoterapia II: Imunonutrition ".).

With relation to the second group of substances, the story is different. These are the chemicals derived from petrolium and heavy metals, both with cumulative properties in the biological systems. In other words, with constant use, they accumulate in the tissues. As they are lipotrofic substances, that is, they concentrate on the fats, they are eliminated essentially through the central organ of the lipídic metabolism - the liver. The kidneys participate basically in the hidroeletrolític balance and of the filtration of hidrosoluble substances, while the liver eliminates, through the bile, in the feces, the toxic liposoluble substances .

Isn’t Urine Dirty and Polluted?

Only when the renal system is attacked by some infection will we find microorganisms in the urine. In a general way the urine is completely a sterile liquid, in other words, exempt of any microorganism.

In the case of a renal infection or of the urinary tracts, the ingestion of those microorganisms present in the urine, would determine a specífic imunológical answer against the infection, by a process that that is called auto-vaccination. This principle is applicable in all the cases and diseases where ones own urine is ingested. In this hypothesis, the antigens and same microorganisms, would be captured by specialized cells of the intestinal mucous membrane - as M cells - and presented to the imunológical system . This information is then appropriately codified and transformed into specific immune actions, in accordance to the antigenic profile present in the urine.

Constitution of urine?

Urine is the filtrate glomerular of the blood, taken from reabsorbed substances after the filtration by the renal tubes and added to other substances secreted by the kidneys.

It contains from 95 to 99% of water and of 1 to 5% of solubles.

Those are usually distributed like this:

Solutos gr. 24 hs.
Ureia 25
Ammonia 0,8
Úric Ácid 0,7
Creatinina 1,5
Creatina 0,8
Amino acids 0,8
Glucose < 0,05
H+ pH 5-8
Na+ 3,0
K+ 1,7
HPO42 - 1,2 G P
SO42 - 1,4 G S
Cl - 6,3
Mg2+ 0,15
Ca2+ 0,2

The information presented is a medium sample of volume of 1200 ml in 24 hs.
The composition and the volume vary , depending on the liquid ingestion and diet.
It possesses, in smaller amounts, in a total of ±200 mg, countless substances that are fisiologically active, in great majority, peptides, that are active in practically all of the organs of the body, as the following examples demonstrate:

Uroquinase - enzyme that has the property of dissolving coagulates in the blood , and used terapeutically in cases of cerebral clots and infarct of the miocárdio;
Eritropoietina - peptíde that stimulates the eritrócitos production (red globules);
Factor of proliferation tissular - it increases the cellular replacement in cases of lesions epiteliais;
Calicreína - hormone peptíde vasodilatador;
D.H.E.A. (deidroepiandrosterona) - hormone precussor of the masculine and feminine sexual hormones;
Melatonina - hormone with antidepressive activity.
Antineoplastons - peptídes that when activated by the pancreátic juice, present anti-tumor activity.
Hormones suprarenais - with anti-inflammatory activities; All the hipofises hormones .

Antigens of the basal membrane of the epiteliais cells and mesenquimais of all the organs, plasmátic and non plasmátic antigens, originating from injuries and pathologies, antigens tumours and antigens due to the microbial degradation and substances produced by infected cells.
And many other substances not yet identified.

Immunonutrition

Introduction

Endogenous Synthesis of Amino Acids

Reintroducing additional amounts of urea and ammonia from urine by mouth, apart from ammonia derived from the intestinal endogenous cycle,[i] large amounts of ammonia reach the liver through the portal vein. The liver plays a central role in removing portal ammonia by two different paths.[ii] One path is by promoting a new synthesis of urea and the other, by glutamine synthesis. Actually, there is not only an increased amount of these two substances, but also of several amino acids,[iii],[iv] which will be addressed separated due to interesting and basic particularities of each amino acid, especially arginine, glutamate/glutamine and glycine, that share important roles in the immune system.

Glutamine

Glutamine: Pivot of Nitrogen Saving

Glutamine has been long classified as a non-essential or nutritionally dispensable amino acid for being endogenously synthesized from other amino acids and precursors at appropriate amounts.[x] However, this concept of glutamine as a dispensable nutrient goes against its qualitative and quantitative importance in the metabolism of mammals. Apart from its role as the structural unit of proteins, glutamine is an amino acid with unique physiologic and biochemical properties. It is the most abundant amino acid in the blood, accounting for 30-35% of nitrogen free amino acids (500-900 µM) in blood. Under certain conditions glutamine represents over 80% of all nitrogen of amino acid carried in the blood.[xi] Since it contains two nitrogen groups that are readily available, a nitrogen a-amino and a nitrogen amide, it is quantitatively the most important non-toxic carrier of nitrogen[xii] and of carbon[xiii] among diverse organs.[xiv]

There is a significant difference in the concentration gradient among the plasma membranes of several tissues, and glutamine is the most important component of intracellular amino acid reserves. In the human skeletal muscle, for instance, the main synthesis and storage organ, in which the concentration of glutamine is 30-fold that of plasma, glutamine represents over 60% of all free amino acid reserves.[xv] Considering that the striated muscles usually have half of all free amino acids of the body, the quantitative importance of this amino acid is evident, and glutamine is the most abundant amino acid, accounting for over 60% of all nitrogen in the body.

Apart from its importance in carbon and nitrogen carrying and storage, glutamine plays a fundamental role in several metabolic paths.[xvi] It is an essential precursor for the biosynthesis of nucleic acids[xvii] of all cells, as well as the major substrate in renal and intestinal ammoniagenesis[xviii]; therefore, it also plays an important role in the acid-base balance.[xix] It is very important in carbohydrate metabolism as a precursor of glycogen[xx] and protein[xxi],[xxii],[xxiii],[xxiv] synthesis and in protein degradation inhibition.[xxv] It is also fundamental as an indispensable substrate for rapid proliferation cells, such as intestinal mucosa cells[xxvi], endothelial[xxvii] and tubular renal[xxviii] cells, fibroblasts[xxix], tumor cells[xxx],[xxxi] and immune system cells.7

Glutamine and the Immune System

Glutamine as a Specific Immune System Substrate

Limphocytes,[xxxii],[xxxiii] macrophages,[xxxiv] neutrophils[xxxv] and probably all immune system cells[xxxvi] depend on glutamine as their primary energy source. Recent evidence has demonstrated that usage rate of glutamine by these cells is similar or even greater than that of glucose, and neither is completely oxydized for energy source. Both are almost completely used for immunoactive biomolecules and nucleotide synthesis for cellular replication.[xxxvii] A high glutamine uptake rate is characteristic of these proliferative cells for synthesis of key molecules, such as glutathione[xxxviii] and nucleic acids, even in immune quiescent conditions. In the absence of glutamine, the lymphocytes do not proliferate in vitro; on the other hand, their proliferation significantly increases with greater glutamine concentration.[xxxix]

The presence of tumor cells in rats promotes increased glutaminase activity in lymphoid organs, and in isolated lymphocytes and macrophages.[xl] The use of glutamine has also been related with production of superoxyde and interleukin-1 and 6 by macrophages[xli], and interleukin-2 by lymphocytes.[xlii]

Lymphocytes have an intense proliferative capacity, apart from immunoglobulin synthesis, whereas macrophages and neutrophils, differentiated cells that have little proliferative capacity, besides their secretory activity, have a great phagocytic capacity and require high lipid synthesis and replacement rates[xliii] for adequate maintenance of the membrane. There is evidence that these cells, mainly macrophages, synthesize lipids of piruvate derived from glutamine metabolism.[xliv],[xlv] There is a study demonstrating that lipids actively participate in immune regulation.[xlvi]

Recent in vitro studies [xlvii],[xlviii],[xlix] and animal studies[l],[li] have shown that glutamine could increase the bactericidal function of neutrophils, which are the phagocytes primarily involved in elimination of invasive bacteria, enhancing their capacity of phagocytosis and producing oxygen reactive metabolites. They capture opsonized bacteria, phagocyte them and later destroy the bacteria with non-oxidizing proteins, combined with intermediate oxygen reactive products, that is, superoxyde (O2-), hydrogen peroxide (H2O2) and hypochoride (OCl-).[lii] Macrophage-mediated phagocytosis is also influenced by glutamine availability;[liii] it increases NK cell activity,[liv] stimulates intestinal production of IgA,[lv] interferon-g and tumor necrosis factor.[lvi],[lvii]

Glutamine and Intestinal Barrier Preservation

The enterocytes are some of the cells that most consume glutamine,[lviii],[lix] due to the rapid proliferation required for its role. The intestine is a digestion and absorption organ as well as a barrier against invasive pathogens and harmful molecules. The phenomenon of bacteria and their endotoxins crossing the undamaged intestinal mucosa barrier and invading extraintestinal tissues (mesenteric lymph nodes, liver, spleen, peritoneal cavity, blood and lymphatic circulation) has been refereed as bacterial translocation.[lx],[lxi] The defense of the gastrointestinal tract apparently involves two components.[lxii] The first component comprises a mechanical and chemical barrier including an acid pH in the stomach, tight epithelial junctions, a mucous layer lining the epithelium and indigenous intestinal microflora. The second defense component is the intestinal lymphoid tissue (ILT). The antigen processing in ILT is part of an elaborate system that promotes secretion of antigen-specific IgA towards the intestinal lumen. It is important to note that the intestinal barrier acts in layers, and even the secretory activity involves three levels[lxiii] (see Table 2).

Table 2: Levels of defense in the intestinal barrier

Local Innate Immune Mechanisms
Gastric acidity
Cleaning effect of intestinal motility
Intraluminal digestive events
Mucous layer attached to epithelium
Tight intercellular junctions among enterocytes
Fast proliferation of enterocytes towards the lumen

Adjustable Immune Mechanisms (Intestinal lymphoid tissue)
Antigen presentation
T-lymphocyte responses
Production of secretory immunoglobulines

Systemic Mechanisms
Refining adjustable immune mechanisms
Macrophagic activity

Adapted from Hall et al.9

The intestinal barrier efficacy may be impaired as a consequence of a series of local and systemic injuries, for reasons not completely understood yet (see Table 3).

Table 3: Intestinal injuries associated to increased bacterial translocation

Systemic Local
Undernourishment Radiation
Shock Chemotherapy
Sepsis Inflammation
Burns Severe diarrhea
Severe traumaInfection
Advanced cancerAntibiotics
Adapted from Souba et al.[lxiv]

These injuries act in a synergistic fashion leading to microvillus atrophy, increased intestinal patency and translocation of luminal bacteria and their toxins. Invasion by intestinal bacteria causes a systemic response of hypermetabolism and hypercatabolism that characterize sepsis and, if persistent, results in multiple failure of organs.

Today there is solid evidence that glutamine plays a fundamental role in maintenance of intestinal metabolism, structure and function. In animal models with enterocolitis, it was demonstrated that glutamine supplementation prolonged survival of these animals and decreased severity of mucosa inflammation.[lxv] Other studies performed in animal models with enterocolitis caused by irradiation showed that glutamine promoted recovery of the injured mucosa and decreased subsequent bacterial translocation, as well as it stimulated the local lymphocytes to better eliminate bacteria from lymph nodes.[lxvi],[lxvii]

Increased Demand Makes Glutamine Essential

Obviously this demand for glutamine is high in immune quiescent situations and it increases significantly when the immune system is activated due to any challenge. The mitogenic activation of lymphocytes enhances both activity of glutaminase and use of glutamine.22

It is known that the plasma and tissue concentrations of glutamine are not only high but also very labile. The plasma glutamine levels present a marked and fast drop in the course of catabolic states, such as surgeries, burns, sepsis, cancer and other systemic diseases.[lxviii],[lxix] During catabolic stress, the intracellular concentration of glutamine might drop by over 50% and the plasma levels by over 30%.[lxx] In patients with hemorragic necrotizing pancreatitis, a decrease by up to 85% was observed,[lxxi] demonstrating that, in such conditions, the demand for glutamine may exceed the capacity of synthesis by the body. This drop in glutamine levels is greater than that of any other amino acid and generally corresponds to severity of the underlying disease. Normal levels are attained only by the end of convalescence, although not easily.[lxxii]

After investigating the physiologic bases of these alterations,[lxxiii],[lxxiv] the anabolic effects related to glutamine supply were described in animal models [lxxv], [lxxvi], [lxxvii] and in humans.[lxxviii],[lxxix] It was then evident that classifying glutamine as a non-essential amino acid would be incorrect, and in the beginning of the 90's, it was proposed to reclassify glutamine as a conditionally essential amino acid.18,[lxxx]

In diseases associated with a drop in glutamine levels, the immune function is usually suppressed.[lxxxi],[lxxxii]

Clinical Supplementation of Glutamine

It has been demonstrated that the exogenous supplementation of glutamine restores the plasma levels and improves immune function. In a prospective, randomized and double-blind study, immunesuppressed patients (due to irradiation and chemotherapy) who received glutamine before bone marrow transplant presented significantly less bacterial contamination and infections than the control group;[lxxxiii] this fact was associated with teh fact T-lymphocytes matured faster in those who received glutamine.[lxxxiv] In another study carried out with patients during the post-operative period, the T-lymphocyte proliferative response increased with administration of parenteral glutamine.[lxxxv] And with intravenous supplementation, improvement in survival of severe patients followed up for six months was demonstrated[lxxxvi], as well as improvement in postoperative nitrogen balance, increased number of peripheral lymphocytes, increased production of leukotrienes by neutrophils, and shorter postoperative period.[lxxxvii] A study with enteral supplementation showed that glutamine significantly reduced the incidence of pneumonia, bacteremia and sepsis in patients with multiple trauma.[lxxxviii]

Arginine

Endogenous Production and Metabolism of Arginine

Arginine Synthesis Via Urea Cycle

Arginine is an amino acid that becomes dispensable only after growth phase and it is very much used by the immune system. It plays a crucial role in tissue scarring and regeneration mechanisms.

The main source of arginine in mammals is the urea cycle. An important detoxification circuit, the urea cycle works not only to make nitrogen excretion easier by means of urea synthesis, but also to increase arginine endogenous supply.

Function of Arginine In Metabolic Economics

Arginine plays a unique role in human nutrition due to its wide range of biological activities. Some studies carried out in the past 40 years have demonstrated that arginine has important metabolic and immunological functions, specially during stress conditions, such as infections.[lxxxix],[xc] These studies put forward the issue of reclassifying arginine, like glutamine, as a "conditionally essential amino acid",[xci] because its demand is greater than supply in hypermetabolism.

Arginine plays a central role in the synthesis of urea and proteins, of high-energy elements, such as creatine, polyamines and nitric oxide (NO).[xcii] When administered in pharmacological doses, it promoted scarring by increasing the production of collagen, stimulating the hormone release of several endocrine glands, regulating growth of some tumors and potentiating immune system cell responses.[xciii]

Arginine and the Immune System

It was suggested that the amino acid arginine would have an imnune nutrient effect in mid 70's, when its immune stimulatory capacity was observed in animals.[xciv] It was shown that arginine was essential in diet in order to maintain body weight, adequate scarring process and survival of rats submitted to injury.[xcv],[xcvi] Increasing evidence that trauma and other injuries, including sepsis, would cause alterations in intra and extracellular concentrations of certain amino acids[xcvii] suggested that dietetic needs of some amino acids would vary in these conditions. Moreover, administration of these amino acids would favorably change the metabolic and physiologic responses to these injuries,[xcviii] probably with concurrent involvement of the hypothalamic-hypophisealis axis.[xcix] Since then the capacity to reduce growth and dissemination of tumors due to immune stimulatory effects is increasingly evident in animal models[c],[ci],[cii],[ciii] and in humans.[civ],[cv] The action of arginine activating lymphocytes,[cvi] neutrophils[cvii] and macrophages is confirmed.[cviii]

Two metabolic paths were identified as responsible for immunemodulating actions of arginine. The first path is through the enzyme arginase, and the final products of it are polyamines, which are fundamental for DNA replication and cell proliferation.[cix] The second path involves a family of enzymes known as NO-synthetases for producing large amounts of NO.[cx] Although its role in unspecific immunity is not completely clear, we know that NO seems to inhibit DNA synthesis and consequent division of unwanted cells[cxi]. It is highly released by activated macrophages and neutrophils, and together with oxygen, it makes highly reactive intermediate compounds, such as the radical hydroxyl (OH), nitrogen dioxide (ONOO-) and other nitric or nitrous compounds that act as endogenous antimicrobial agents.[cxii]

Several clinical studies have assessed the efficacy of arginine in intensifying the immune mechanisms in burn patients with infections,[cxiii] in patients with cancer,[cxiv] immunesuppressed patients[cxv] and those submitted to surgery/trauma.[cxvi],[cxvii] The best results were observed in the last group.

Glycine

Endogenous Production and Metabolism of Glycine

The New Anti-Inflammatory Immunenutrient

Glycine could be produced by a glycolysis intermediate compound, with subsequent conversion of the amino acid serine, or, in the liver, by action of the enzyme glycine synthetase, which incorporates one ammonia molecule and helps to detoxify the body from ammonia (Review Lehninger).

Glycine prolongs survival of rats in endotoxemic shock.[cxviii] It also minimizes the alcohol-induced hepatic lesions, in vivo, reducing ethanol that goes to the liver, making the first step of its metabolism in stomach quicker,[cxix] and improving recovery from alcoholic hepatitis[cxx] and survival of liver transplantation.[cxxi] It reduces fibrosis caused by experimental drugs, preventing hepatic injury[cxxii] and chemical-induced hepatic cell proliferation.[cxxiii] Thus, glycine inhibits growth of tumors caused by cell implantation of melanoma in animal models.[cxxiv] It reduces nephrotoxicity of cyclosporin A[cxxv] and avoids hypoxia and formation of free radicals.[cxxvi]

Glycine and the Immune System

Glycine-Dependent Chlorine Channels In Leukocytes

Most actions of glycine are due to chlorine channel block related to glycine, as recently described in Kupffer cells[cxxvii]; it seems to be common to all leukocyte populations.[cxxviii]

Due to the feature of glycine-dependent chlorine channel, glycine has been correlated with immnuregulatory functions, ranging from antitumor to immunosuppressive activities. Based on experimental evidence, its clinical use was suggested in some cases, varying from sepsis to endotoxemy, respiratory distress syndrome to asthma and as adjuvant in transplants and oncologic cases.[cxxix]

Glycine and Cancer

A study with mice with implanted tumor cells (melanoma B16) showed a significant difference in tumor growth. In individuals receiving a diet with 5% glycine and 15% casein, as compared with 20% casein in the control group, the tumors were 65% lighter, mainly after 14-day follow-up, and this suggested that glycine would play a fundamental role in inhibition of angiogenesis and vascularization of tumors. Actually, glycine inhibits in vitro growth of endothelial cells, corroborating the hypothesis that glycine would inhibit in vivo tumor growth by mechanisms involving endothelial proliferation control.121, 126

Conclusion

Nitrogen metabolism in the gastrointestinal tract involves complex cycles in systemic circulation, mucosa and intraluminal reserves of proteins, amino acids and other endogenous and diet-derived nitrogen materials. And the intestinal microflora is interposed in these cycles, with its microbial reserves of nitrogen, besides its own nutritional needs that are satisfied by degradation of food and endogenous substances. Urea may be included in bacterial growth substrates, provided that the bacterial population has urease, which allows urea penetrating the intestinal lumen to be degraded and supply nitrogen (as ammonia) for the microbial synthesis of amino acids and proteins, or for the endogenous synthesis of amino acids. Despite the fact that this recycling influences the composition of amino acids, and therefore, quality of the protein available to meet the diverse nutritional requirements, the actual nutritional contribution for the host for reusing inorganic N is not exactly clear,[cxxx] considering ingestion of extra amounts derived from urine.

In individuals with normal diet, approximately three-quarters of urea produced is excreted in the urine. The remaining one-quarter goes to the digestive tract through physiological secretions and suffers hydrolysis by the intestinal microflora, and nitrogen is available for further metabolic interaction.[cxxxi] Nevertheless, since there is much interindividual variability within the protein metabolism, it is related to urea kinetics and, a variation coefficient is usually considered ≈ 35% for production and excretion of urea.[cxxxii]

Concerning quantification of amino acids produced from this fraction of inorganic N (≈ 25%), the few studies available interestingly show a greater production of glutamine (≈ 48%), arginine (≈ 40%) and glycine (≈ 4%).3,4

These data on synthesis and metabolic importance of these amino acids, formed from some of the most abundant non-protein nitrogen substances of urine (urea and ammonia), would explain some favorable responses of urine given by the mouth observed in our medical practice, such as a significant improvement in immune function.

A first practical observation is that urine excreted after ingestion has less urea than that drunk, since it is less concentrated. And after some reingestions, the urine is clear and has no odor at all, that is, has no solutes. These data inform that there is retention of solids in urine, and it occurs because of the intestinal flora and its correct enzymatic apparatus.

Another important piece of information concerns the feeling of well being derived from the practice of reusing urine. If this activity were harmful to the body or an attack against our own health, we would present progressive intoxication conditions, such as uremia. But the opposite situation is observed. There is improvement of disposition and mood, significant improvement in quality of sleep, and better immune resistance, with ready responses to several diseases, ranging from infections to degenerative conditions.

Unfortunately, we have had no conditions to investigate more these facts by means of our own study protocol. A double-blind, randomized study is probably not feasible, since a placebo that imitates the characteristic and complex flavor of urine would be difficult to find. We hope that in a not remote future we can present organized clinical data to better explain about urine therapy. Undoubtedly, there is a long way ahead.

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Urine Therapy: a Physiological Practice?

The centuries-old practice of urine therapy reappears in modern times with several books, organizations and Internet sites on the subject coming out. However, there is not much in scientific terms. This essay very modestly tries to be a starting point.

When drinking urine, one will certainly ask if something our body eliminates would not cause us any damage? What about the "toxic" substances, in this case, "nitrogen excreting products", such as urea, uric acid and ammonia? Why should we reintroduce them in the body? Would they be reusable? We bring up a discussion on this issue below. Unlike what was assumed some years ago, today we know that we can recycle nitrogen helped by the intestinal microflora.

Reusing Urine Inorganic Nitrogen

The non-protein nitrogen cycle in the intestine

During the process of diet protein digestion, nitrogen goes from intestine to the body. However there is a simultaneous movement of nitrogenated substances towards the intestinal lumen. These substances come from different sources: saliva, pancreatic juice, bile, cell debris, transluminal urea secretion, mother's milk or, in drunken urine, the issue here addressed.

Most non-protein nitrogen released inside the digestive tract is digested and reabsorbed, and only a small amount of this nitrogen is excreted through stools. However, much substance is recycled in a different manner due to the intestinal microbiota, which has enzymes the hosts do not have, and change the non-protein nitrogenated substrates into substances we could assimilate. Through ammonia, a product of urea breakdown by bacterial ureases - this N that was not available before is now used for endogenous protein synthesis or microbial protein synthesis, thus providing essential amino acids produced by the intestinal flora

Introduction

The living beings present considerable differences regarding their capacity to synthesize 20 different amino acids. They also differ on nitrogen forms used as amino acid precursor. Humans, for instance, are able to synthesize only ten out of 20 amino acids essential for protein biosynthesis. The microorganisms greatly differ about their ability to synthesize amino acids. Most Enterobacteriaceae, except Lactobacillus, are able to synthesize from simple precursors all 20 amino acids needed for protein synthesis1 . Urea, for instance, a small molecule with two nitrogen atoms, is our main excretion product and can not be directly reused by us, since we lack urease, an enzyme that breaks urea down in two ammonia molecules. Ammonia is very useful for us. The ten amino acids known as nonessential or dispensable, are synthesized by humans from ammonia and several carbon sources. The other ten amino acids, the so-called essential or indispensable amino acids, may be obtained through diet, or as we now know, by means of microbial synthesis of amino acids, which synthesize all 20 amino acids in our intestine

Urea and Ammonia: Recycling Nitrogen

Urea is the final component of the nitrogenated catabolism of mammals and the non-protein nitrogenated substance of higher concentration in digestive secretions2, mother's milk3 and urine4 . It may not be metabolized by macroorganisms, unless through metabolic processes of microorganisms that contain urease5, which hydrolyzes urea and releases ammonia, based on the reaction:

CO(NH2)2 + H2O ® 2NH3 + CO2.

Ammonia (NH3) released by bacterial urease6, taken in by portal vein, provides nitrogen for the endogenous synthesis of dispensable (or nonessential) amino acids, mainly by means of the hepatic synthesis of glutamine and glutamate7.

Endogenous production of amino acids with recycled N from ammonia

It is well known that in individuals with an adequate intake of protein, ≈ 60-70% of urea produced by metabolism is excreted in urine, whereas the remaining 30-40%, secreted in the gastrointestinal tract, are recycled through degradation by intestinal microbial urease.8,9 This action of urease allows 20-50% of nitrogen from urea hydrolyzed in ammonia to be recycled and return to the body as amino acids, while 50-80% return as urea via ureagenesis.10,11 The amount of recycled non-protein nitrogen is inversely proportional to consumption of protein nitrogen, that is, the less protein in diet, the more efficient the non-protein nitrogen recycling process.12,13 However, nitrogenated balance is achieved, or becomes positive when non-protein N is supplied in reasonably high amount.14

In studies with human milk, which contains 20-25% non-protein N, including urea, uric acid and creatinine, a retention rate of up to 60% was observed for 15N of urea.3,15.

In adults, the studies demonstrated a physiological re-use of total urea of approximately 25-40%, depending on diet, concurrent disease, growth phase and microbiological adaptation, among other factors.2,8,9,10,16,17 Considering this percentage, a N re-use of more than 80% in the synthesis of new amino acids was demonstrated.14

There is evidence of increase in glutamine levels, as well as arginine, alanine, glycine, serine and others, in descendant order.18

Moreover, the kidneys are organs that contribute much to this recycling, adding ammonia to the body. Only 30% of the renal production of ammonia are released in urine, and the remaining 70% are released in the renal vein. 19

Production of Indispensable Amino Acids by the Intestinal Microbiota

Urea is usually secreted in the digestive tract by saliva, bile and gastric juice, but it freely circulates in the stomach and intestines (transluminal secretion), and the colon is patent to it, although less pervious than the small intestine.13,20,21

However most urea come from bile and pancreatic juice. The transluminal secretion is greater in jejune than in the ileum, and there is not much urea in the cecum2. There are data demonstrating, for instance, that only 8% of plasma urea derived from fecal ammonia N (colon), and most of it came from the small intestine.22

It is traditionally accepted that most of the microbial population is found in the colon and that the small intestine is the site of greatest absorption of amino acids. That is true, but the small intestine is not the sole site of amino acid absorption, neither is the microbial activity confined to the colon.23 Therefore, it was assumed that microbial proteins would not be able to play any functional role in non-ruminants, as they play in ruminants.

Part of amino acid absorption occurs in the colon,19 but it seems more likely to take place in the small intestine.24 Much microbiological activity occurs in this area,21 due to a large amount of urea secreted in the initial portions of the small intestine. The ileum may have a metabolism rate of up to 38% of total urea.3

Studies in animals19,24,25 and in humans 8,17,18,26,27,28,29 demonstrated labeled nitrogen in essential amino acids, such as arginine, valine, leucine, phenylalanine, lysine, histidine and threonine. Although the production of threonine is one of the lowest among 15N-labeled amino acids and minimal requirement estimates are under discussion30, it is 3 to 7-fold greater than that required by international standards for human adults currently accepted.31

Ureia ® (microflora) ® ammonia ® (macroorganism) ®
® nonessential aa. ® (microflora) ® essential aa.

It seems that the microflora does not use only ammoniacal N from urea breakdown, but mostly N recycled through dispensable amino acid synthesis, mainly in the liver, and returned to the small intestine in protein-rich endogenous secretions. Then it is reused by the microflora2,32, in the synthesis of essential amino acids, which will be finally absorbed and used in protein synthesis. Therefore, the microorganisms would find the amino acid structures better defined.

Subestimating Recycling

Although there is more evidence of recycling, we know that these estimates are very distorted, and they are probably underestimates. Measurements are taken in plasma 15N-labeled amino acids, due to easy access, and intracellular and interstitial amino acids are not used. Amino acids are formed through intracellular metabolic paths; therefore their concentration (particularly glutamine and alanine, the main products of nitrogenated incorporation) is higher inside cells than in plasma 33. There is another severe and important distortion. The new synthesized amino acids, labeled with 15N, may be incorporated to proteins instead of continuing in plasma, and escaping from nitrogenated incorporation.29

Conclusion

These data demonstrate that this capacity to recycle, much studied in ruminants, is present in humans, and it has shown to physiological, and even necessary, because urea represents ≈ 15% of nitrogen in human milk.

Since urea is the main product of N catabolism, this urea N recovery and recycling process shall have a considerable impact not only on nitrogenated balance, but also on the specific metabolic functions these amino acids have in the body.

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Advice: Urine Therapy is a concept which should not be practiced by individuals without sufficient knowledge, no one should rely on single person's (doctor, consultant, therapist) opinion, consult with other practitioners before taking such step, this would may help you avoid health complication in future.

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