NUTRIFLEX OMEGA PLUS EMULSION FOR INFUSION

Indication

Used for nutritional supplementation, also for treating dietary shortage or imbalance.

Mechanism of Action

Many of supplemental L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase. NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium. All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range. The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid^would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, supplemental L-arginine could enhance endothelial-dependent vasodilation and NO production.

Pharmacokinetics

Absorption

Absorbed from the lumen of the small intestine into the enterocytes. Absorption is efficient and occurs by an active transport mechanism.

Distribution

Metabolism

Some metabolism of L-arginine takes place in the enterocytes. L-arginine not metabolized in the enterocytes enters the portal circulation from whence it is transported to the liver, where again some portion of the amino acid is metabolized.

Elimination

Toxicity

Oral supplementation with L-arginine at doses up to 15 grams daily are generally well tolerated. The most common adverse reactions of higher doses from 15 to 30 grams daily are nausea, abdominal cramps and diarrhea. Some may experience these symptoms at lower doses.

Active Ingredient/Synonyms

(2S)-2-amino-5-(carbamimidamido)pentanoic acid | (2S)-2-amino-5-guanidinopentanoic acid | (S)-2-amino-5-guanidinopentanoic acid | (S)-2-Amino-5-guanidinovaleric acid | Arg | Arginine | L-(+)-Arginine | L-Arg | L-Arginin | R | L-Arginine |

Indication

There is no support for the claim that aspartates are exercise performance enhancers, i.e. ergogenic aids.

Mechanism of Action

There are also claims that L-aspartate has ergogenic effects, that it enhances performance in both prolonged exercise and short intensive exercise. It is hypothesized that L-aspartate, especially the potassium magnesium aspartate salt, spares stores of muscle glycogen and/or promotes a faster rate of glycogen resynthesis during exercise. It has also been hypothesized that L-aspartate can enhance short intensive exercise by serving as a substrate for energy production in the Krebs cycle and for stimulating the purine nucleotide cycle.

Pharmacokinetics

Absorption

Absorbed from the small intestine by an active transport process

Distribution

Metabolism

Elimination

Toxicity

Mild gastrointestinal side effects including diarrhea. LD₅₀ (rat) > 5,000 mg/kg.

Active Ingredient/Synonyms

(S)-2-aminobutanedioic acid | (S)-2-aminosuccinic acid | 2-Aminosuccinic acid | Asp | Aspartic acid | D | L-Asp | L-Asparaginsaeure | L-Asparaginsäure | L-Aspartate | L-Aspartic acid | L-Aspartic Acid |

Indication

Used for nutritional supplementation, also for treating dietary shortage or imbalance. Used to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older [FDA Label].

Mechanism of Action

Supplemental L-glutamine's possible immunomodulatory role may be accounted for in a number of ways. L-glutamine appears to play a major role in protecting the integrity of the gastrointestinal tract and, in particular, the large intestine. During catabolic states, the integrity of the intestinal mucosa may be compromised with consequent increased intestinal permeability and translocation of Gram-negative bacteria from the large intestine into the body. The demand for L-glutamine by the intestine, as well as by cells such as lymphocytes, appears to be much greater than that supplied by skeletal muscle, the major storage tissue for L-glutamine. L-glutamine is the preferred respiratory fuel for enterocytes, colonocytes and lymphocytes. Therefore, supplying supplemental L-glutamine under these conditions may do a number of things. For one, it may reverse the catabolic state by sparing skeletal muscle L-glutamine. It also may inhibit translocation of Gram-negative bacteria from the large intestine. L-glutamine helps maintain secretory IgA, which functions primarily by preventing the attachment of bacteria to mucosal cells. L-glutamine appears to be required to support the proliferation of mitogen-stimulated lymphocytes, as well as the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). It is also required for the maintenance of lymphokine-activated killer cells (LAK). L-glutamine can enhance phagocytosis by neutrophils and monocytes. It can lead to an increased synthesis of glutathione in the intestine, which may also play a role in maintaining the integrity of the intestinal mucosa by ameliorating oxidative stress. The exact mechanism of the possible immunomodulatory action of supplemental L-glutamine, however, remains unclear. It is conceivable that the major effect of L-glutamine occurs at the level of the intestine. Perhaps enteral L-glutamine acts directly on intestine-associated lymphoid tissue and stimulates overall immune function by that mechanism, without passing beyond the splanchnic bed. The exact mechanism of L-glutamine's effect on NAD redox potential is unknown but is thought to involve increased amounts of reduced glutathione made available by glutamine supplementation [FDA Label]. This improvement in redox potential reduces the amount of oxidative damage which sickle red blood cells are more susceptible to. The reduction in cellular damage is thought to reduce chronic hemolysis and vaso-occlusive events.

Pharmacokinetics

Absorption

Absorption is efficient and occurs by an active transport mechanism. Tmax is 30 minutes after a single dose [FDA Label]. Absorption kinetics following multiple doses has not yet been determined.

Distribution

Volume of distribution is 200 mL/kg after intravenous bolus dose [FDA Label].

Metabolism

Exogenous L-glutamine likely follows the same metabolic pathways as endogenous L-glutamine which is involved in the formation of glutamate, proteins, nucleotides, and amino acid sugars [FDA Label].

Elimination

Toxicity

Doses of L-glutamine up to 21 grams daily appear to be well tolerated. Reported adverse reactions are mainly gastrointestinal and not common. They include constipation and bloating. There is one older report of two hypomanic patients whose manic symptoms were exacerbated following the use of 2 to 4 grams daily of L-glutamine. The symptoms resolved when the L-glutamine was stopped. These patients were not rechallenged, nor are there any other reports of this nature. The most common adverse effects observed in clinical trials of Endari were constipation (21%), nausea (19%), headache (18%), abdominal pain (17%), cough (16%), extremity pain (13%), back pain (12%), and chest pain (12%) [FDA Label].

Active Ingredient/Synonyms

(2S)-2-amino-4-carbamoylbutanoic acid | (2S)-2,5-diamino-5-oxopentanoic acid | (S)-2,5-diamino-5-oxopentanoic acid | Glutamic acid 5-amide | Glutamic acid amide | Glutamine | L-(+)-glutamine | L-2-aminoglutaramic acid | L-glutamic acid γ-amide | L-Glutamin | L-Glutaminsäure-5-amid | Levoglutamide | Q | L-Glutamine |

Indication

Supplemental glycine may have antispastic activity. Very early findings suggest it may also have antipsychotic activity as well as antioxidant and anti-inflammatory activities.

Mechanism of Action

In the CNS, there exist strychnine-sensitive glycine binding sites as well as strychnine-insensitive glycine binding sites. The strychnine-insensitive glycine-binding site is located on the NMDA receptor complex. The strychnine-sensitive glycine receptor complex is comprised of a chloride channel and is a member of the ligand-gated ion channel superfamily. The putative antispastic activity of supplemental glycine could be mediated by glycine's binding to strychnine-sensitive binding sites in the spinal cord. This would result in increased chloride conductance and consequent enhancement of inhibitory neurotransmission. The ability of glycine to potentiate NMDA receptor-mediated neurotransmission raised the possibility of its use in the management of neuroleptic-resistant negative symptoms in schizophrenia.
Animal studies indicate that supplemental glycine protects against endotoxin-induced lethality, hypoxia-reperfusion injury after liver transplantation, and D-galactosamine-mediated liver injury. Neutrophils are thought to participate in these pathologic processes via invasion of tissue and releasing such reactive oxygen species as superoxide. In vitro studies have shown that neutrophils contain a glycine-gated chloride channel that can attenuate increases in intracellular calcium and diminsh neutrophil oxidant production. This research is ealy-stage, but suggests that supplementary glycine may turn out to be useful in processes where neutrophil infiltration contributes to toxicity, such as ARDS.

Pharmacokinetics

Absorption

Absorbed from the small intestine via an active transport mechanism.

Distribution

Metabolism

Hepatic

Elimination

Toxicity

ORL-RAT LD₅₀ 7930 mg/kg, SCU-RAT LD₅₀ 5200 mg/kg, IVN-RAT LD₅₀ 2600 mg/kg, ORL-MUS LD₅₀ 4920 mg/kg; Doses of 1 gram daily are very well tolerated. Mild gastrointestinal symptoms are infrequently noted. In one study doses of 90 grams daily were also well tole.

Active Ingredient/Synonyms

Aminoacetic acid | Aminoessigsäure | Aminoethanoic acid | Gly | Glycin | Glycocoll | Glykokoll | Glyzin | Leimzucker | Glycine |

Indication

The branched-chain amino acids may have antihepatic encephalopathy activity in some. They may also have anticatabolic and antitardive dyskinesia activity.

Mechanism of Action

(Applies to Valine, Leucine and Isoleucine)
This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet. The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with a-ketoglutarate as amine acceptor. As a result, three different a-keto acids are produced and are oxidized using a common branched-chain a-keto acid dehydrogenase, yielding the three different CoA derivatives. Subsequently the metabolic pathways diverge, producing many intermediates.
The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoA; thus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic.
There are a number of genetic diseases associated with faulty catabolism of the BCAAs. The most common defect is in the branched-chain a-keto acid dehydrogenase. Since there is only one dehydrogenase enzyme for all three amino acids, all three a-keto acids accumulate and are excreted in the urine. The disease is known as Maple syrup urine disease because of the characteristic odor of the urine in afflicted individuals. Mental retardation in these cases is extensive. Unfortunately, since these are essential amino acids, they cannot be heavily restricted in the diet; ultimately, the life of afflicted individuals is short and development is abnormal The main neurological problems are due to poor formation of myelin in the CNS.

Pharmacokinetics

Absorption

Absorbed from the small intestine by a sodium-dependent active-transport process

Distribution

Metabolism

Hepatic

Elimination

Toxicity

Symptoms of hypoglycemia, increased mortality in ALS patients taking large doses of BCAAs

Active Ingredient/Synonyms

(2S,3S)-2-Amino-3-methylpentanoic acid | 2-Amino-3-methylvaleric acid | alpha-amino-beta-methylvaleric acid | I | Ile | Isoleucine | L-Isoleucine | α-amino-β-methylvaleric acid | L-Isoleucine |

Indication

Indicated to assist in the prevention of the breakdown of muscle proteins that sometimes occur after trauma or severe stress.

Mechanism of Action

This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet. The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with a-ketoglutarate as amine acceptor. As a result, three different a-keto acids are produced and are oxidized using a common branched-chain a-keto acid dehydrogenase, yielding the three different CoA derivatives. Subsequently the metabolic pathways diverge, producing many intermediates. The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoA; thus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic. There are a number of genetic diseases associated with faulty catabolism of the BCAAs. The most common defect is in the branched-chain a-keto acid dehydrogenase. Since there is only one dehydrogenase enzyme for all three amino acids, all three a-keto acids accumulate and are excreted in the urine. The disease is known as Maple syrup urine disease because of the characteristic odor of the urine in afflicted individuals. Mental retardation in these cases is extensive. Unfortunately, since these are essential amino acids, they cannot be heavily restricted in the diet; ultimately, the life of afflicted individuals is short and development is abnormal The main neurological problems are due to poor formation of myelin in the CNS.

Active Ingredient/Synonyms

(2S)-2-Amino-4-methylpentanoic acid | (2S)-alpha-2-Amino-4-methylvaleric acid | (2S)-alpha-Leucine | (S)-(+)-Leucine | (S)-Leucine | 2-Amino-4-methylvaleric acid | L | L-Leucin | L-Leuzin | Leu | Leucine | L-Leucine |

Indication

Supplemental L-lysine has putative anti-herpes simplex virus activity. There is preliminary research suggesting that it may have some anti-osteoporotic activity.

Mechanism of Action

Proteins of the herpes simplex virus are rich in L-arginine, and tissue culture studies indicate an enhancing effect on viral replication when the amino acid ratio of L-arginine to L-lysine is high in the tissue culture media. When the ratio of L-lysine to L-arginine is high, viral replication and the cytopathogenicity of herpes simplex virus have been found to be inhibited. L-lysine may facilitate the absorption of calcium from the small intestine.

Pharmacokinetics

Absorption

Absorbed from the lumen of the small intestine into the enterocytes by an active transport process

Distribution

Metabolism

Hepatic

Elimination

Active Ingredient/Synonyms

(S)-2,6-diaminohexanoic acid | (S)-lysine | (S)-α,ε-diaminocaproic acid | 6-ammonio-L-norleucine | L-2,6-Diaminocaproic acid | L-lys | L-Lysin | LYS | Lysina | Lysine | Lysine acid | Lysinum | L-Lysine |

Indication

Used as magnesium salf-containing laxatives to prevent constipation. It can bring synergistic effect to restore normal bowel function when using in combination with aluminum salts that induce bowel retention [T28]. Magnesium acetate tetrahydrate is used as a source of water and electrolytes when combined with dextrose and other salts to form intravenous infusions. This injection can be used for patients with carbohydrate or magnesium deficiency, insulin hypoglycemia, constipation or hypertension during pregnancy.

Mechanism of Action

Magnesium ions electrostatically stabilize the adenylyl cyclase complex and enhance its catalytic actions and production of cAMP. They also regulate the level of phosphorylation in various pathways by formation of transition state of phosphoryl transfer reaction by protein kinases and stabilize ATP binding to protein kinases via electrostatic interactions [A19416]. Many metabolic enzymes involved in glycolysis and Krebs cycle are magnesium-dependent. Magnesium-containing laxatives cause diarrhea through water retention and increased fecal mass that stimulates peristalsis. When used as an electrolyte supplementation, magnesium acetate tetrahydrate induces diuresis and metabolic alkalinizing effect. Magnesium ions enhance reactivity of arteries to vasoconstrictors, promotes vasoconstriction, and increases peripheral resistance, leading to increased blood pressure [A19412] through potential competition with calcium ions in the vascular system. Magnesium ions also regulate other ions entering and exiting the cell membrane by acting as a ligand in N-methyl-D-aspartate receptor.

Pharmacokinetics

Absorption

Intestinal absorption is achieved mainly through passive diffusion.

Distribution

Magnesium ions display approximate volume of distribution of 0.2 to 0.4 L/kg

Metabolism

Elimination

Toxicity

Predicted oral LD50 value is >2000mg/kg. In case of mild to moderate toxicity, it may cause irritation in case of skin or eye contact,and nausea or vomiting from ingestion and inhalation. In overdose, magnesium impairs neuromuscular transmission, manifested as weakness and hyporeflexia. Early manifestations of severe toxicity are lethargy, hyporeflexia, followed by weakness, paralysis, hypotension, ECG changes (prolonged PR and QRS intervals), CNS depression, seizures, and respiratory depression.

Active Ingredient/Synonyms

Acetic acid, magnesium salt, tetrahydrate | Magnesium diacetate tetrahydrate | Magnesium acetate tetrahydrate |

Indication

Used for protein synthesis including the formation of SAMe, L-homocysteine, L-cysteine, taurine, and sulfate.

Mechanism of Action

The mechanism of the possible anti-hepatotoxic activity of L-methionine is not entirely clear. It is thought that metabolism of high doses of acetaminophen in the liver lead to decreased levels of hepatic glutathione and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may have antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. Antioxidant activity of L-methionine and metabolites of L-methionine appear to account for its possible anti-hepatotoxic activity. Recent research suggests that methionine itself has free-radical scavenging activity by virtue of its sulfur, as well as its chelating ability.

Pharmacokinetics

Absorption

Absorbed from the lumen of the small intestine into the enterocytes by an active transport process.

Distribution

Metabolism

Hepatic

Elimination

Toxicity

Doses of L-methionine of up to 250 mg daily are generally well tolerated. Higher doses may cause nausea, vomiting and headache. Healthy adults taking 8 grams of L-methionine daily for four days were found to have reduced serum folate levels and leucocytosis. Healthy adults taking 13.9 grams of L-methionine daily for five days were found to have changes in serum pH and potassium and increased urinary calcium excretion. Schizophrenic patients given 10 to 20 grams of L-methionine daily for two weeks developed functional psychoses. Single doses of 8 grams precipitated encephalopathy in patients with cirrhosis.

Active Ingredient/Synonyms

(2S)-2-amino-4-(methylsulfanyl)butanoic acid | (S)-2-amino-4-(methylthio)butanoic acid | (S)-2-amino-4-(methylthio)butyric acid | (S)-methionine | L-(−)-methionine | L-a-Amino-g-methylthiobutyric acid | L-Methionin | L-Methionine | L-α-amino-γ-methylmercaptobutyric acid | M | Met | Methionine |

Indication

L-phenylalanine may be helpful in some with depression. It may also be useful in the treatment of vitiligo. There is some evidence that L-phenylalanine may exacerbate tardive dyskinesia in some schizophrenic patients and in some who have used neuroleptic drugs.

Mechanism of Action

The mechanism of L-phenylalanine's putative antidepressant activity may be accounted for by its precursor role in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.
The mechanism of L-phenylalanine's possible antivitiligo activity is not well understood. It is thought that L-phenylalanine may stimulate the production of melanin in the affected skin

Pharmacokinetics

Absorption

Absorbed from the small intestine by a sodium dependent active transport process.

Distribution

Metabolism

Hepatic. L-phenylalanine that is not metabolized in the liver is distributed via the systemic circulation to the various tissues of the body, where it undergoes metabolic reactions similar to those that take place in the liver.

Elimination

Toxicity

L-phenylalanine will exacerbate symptoms of phenylketonuria if used by phenylketonurics. L-phenylalanine was reported to exacerbate tardive dyskinesia when used by some with schizophrenia.

Active Ingredient/Synonyms

(S)-2-Amino-3-phenylpropionic acid | (S)-alpha-Amino-beta-phenylpropionic acid | 3-phenyl-L-alanine | beta-Phenyl-L-alanine | F | Phe | Phenylalanine | β-phenyl-L-alanine | L-Phenylalanine |

Indication

L-Proline is extremely important for the proper functioning of joints and tendons and also helps maintain and strengthen heart muscles.

Mechanism of Action

Glycogenic, by L-Proline oxidase in the kidney, it is ring-opened and is oxidized to form L-Glutamic acid. L-Ornithine and L-Glutamic acid are converted to L-Proline via L-Glutamic acid-gamma-semialdehyde. It is contained abundantly in collagen, and is intimately involved in the function of arthrosis and chordae.

Active Ingredient/Synonyms

(-)-2-Pyrrolidinecarboxylic acid | (−)-(S)-proline | (−)-2-pyrrolidinecarboxylic acid | (−)-proline | (2S)-pyrrolidine-2-carboxylic acid | (S)-2-Carboxypyrrolidine | (S)-2-Pyrrolidinecarboxylic acid | (S)-pyrrolidine-2-carboxylic acid | 2-Pyrrolidinecarboxylic acid | L-(−)-proline | L-alpha-pyrrolidinecarboxylic acid | L-Prolin | L-pyrrolidine-2-carboxylic acid | L-α-pyrrolidinecarboxylic acid | P | Prolina | Proline | Prolinum | L-Proline |

Indication

Used as a natural moisturizing agent in some cosmetics and skin care products.

Mechanism of Action

L-Serine plays a role in cell growth and development (cellular proliferation). The conversion of L-serine to glycine by serine hydroxymethyltransferase results in the formation of the one-carbon units necessary for the synthesis of the purine bases, adenine and guanine. These bases when linked to the phosphate ester of pentose sugars are essential components of DNA and RNA and the end products of energy producing metabolic pathways, ATP and GTP. In addition, L-serine conversion to glycine via this same enzyme provides the one-carbon units necessary for production of the pyrimidine nucleotide, deoxythymidine monophosphate, also an essential component of DNA.

Active Ingredient/Synonyms

(S)-2-Amino-3-hydroxypropanoic acid | (S)-Serine | alpha-Amino-beta-hydroxypropionic acid | beta-Hydroxyalanine | L-Serine | Ser | Serina | Serinum | Serine |

Indication

This intravenous solution is indicated for use in adults and pediatric patients as a source of electrolytes and water for hydration. Also, designed for use as a diluent and delivery system for intermittent intravenous administration of compatible drug additives.

Mechanism of Action

Sodium and chloride — major electrolytes of the fluid compartment outside of cells (i.e., extracellular) — work together to control extracellular volume and blood pressure. Disturbances in sodium concentrations in the extracellular fluid are associated with disorders of water balance.

Pharmacokinetics

Absorption

Absorption of sodium in the small intestine plays an important role in the absorption of chloride, amino acids, glucose, and water. Chloride, in the form of hydrochloric acid (HCl), is also an important component of gastric juice, which aids the digestion and absorption of many nutrients.

Distribution

The volume of distribution is 0.64 L/kg.

Metabolism

The salt that is taken in to gastro intestinal tract remains for the most part unabsorbed as the liquid contents pass through the stomach and small bowel. On reaching the colon this salt, together with the water is taken in to the blood. As excesses are absorbed the kidney is constantly excreting sodium chloride, so that the chloride level in the blood and tissues remains fairly constant.Further more, if the chloride intake ceases, the kidney ceases to excrete chlorides. Body maintains an equilibrium retaining the 300gm of salt dissolved in the blood and fluid elements of the tissue dissociated into sodium ions and chloride ions.

Elimination

Toxicity

The rare inadvertent intravascular administration or rapid intravascular absorption of hypertonic sodium chloride can cause a shift of tissue fluids into the vascular bed, resulting in hypervolemia, electrolyte disturbances, circulatory failure, pulmonary embolism, or augmented hypertension. ( toxnet)

Active Ingredient/Synonyms

Sodium Chloride | Sodium Chloride |

Indication

Used to destroy or kill the nail matrix (matrixectomies) [L1968].

Mechanism of Action

Because of its high-level alkalinity, sodium hydroxide in aqueous solution directly causes bond breakage in proteins (especially disulfide bridges). Hair and fingernails are found to be dissolved after 20 hours of direct contact with sodium hydroxide at pH values higher than 9.2 [L1975]. Sodium hydroxide has depilatory effects which have been described after accidental contact with solutions in the workplace. The breakage of bonds in proteins may lead to severe necrosis to the application site. The level of corrosion depends on the period of contact with the tissue, and on the concentration of sodium hydroxide [L1975].

Pharmacokinetics

Absorption

There are no quantitative data for the absorption of sodium hydroxide through the skin. Solutions which contain 50 % sodium hydroxide have been shown to be corrosive and lethal when applied dermally to mice [L1977].

Distribution

Metabolism

Elimination

Toxicity

Human poisoning cases indicate that a dose of 10 grams orally is fatal [L1970]. Sodium hydroxide is toxic by oral ingestion [L1965]. Sodium hydroxide is corrosive to all tissues. Concentrated vapors lead to serious damage to the eyes and respiratory system. Oral ingestion of sodium hydroxide, which occurs frequently in children, causes severe tissue necrosis, with stricture formation of the esophagus, often resulting in death. Contact with the skin may result in contact dermatitis, hair loss, as well as necrosis due to severe irritation [L1972]. Increased incidence of esophageal carcinoma after severe intoxication with sodium hydroxide has been reported in man. In animal studies, long-term dermal contact with substances leading to pH changes in the skin causes the development of tumors, as a result of severe tissue irritation and reparative cell growth [L1977]. Mutagenic for mammalian somatic cells. May cause damage to the following organs: mucous membranes, upper respiratory tract, skin, eyes [MSDS]. Tumors are not to be expected if the effects of irritation are prevented [L1977]. To date, there are no relevant studies of the prenatal toxic effects of sodium hydroxide [L1977].

Active Ingredient/Synonyms

caustic soda | lye | soda lye | sodium hydrate | white caustic | Sodium hydroxide |

Indication

L-Threonine makes up collagen, elastin, and enamel protein. It aids proper fat metabolism in the liver, helps the digestive and intestinal tracts function more smoothly, and assists in metabolism and assimilation.

Mechanism of Action

L-Threonine is a precursor to the amino acids glycine and serine. It acts as a lipotropic in controlling fat build-up in the liver. May help combat mental illness and may be very useful in indigestion and intestinal malfunctions. Also, threonine prevents excessive liver fat. Nutrients are more readily absorbed when threonine is present.

Active Ingredient/Synonyms

(2S,3R)-(-)-Threonine | (2S)-threonine | 2-Amino-3-hydroxybutyric acid | L-(-)-Threonine | L-2-Amino-3-hydroxybutyric acid | L-alpha-amino-beta-hydroxybutyric acid | L-Threonin | L-α-amino-β-hydroxybutyric acid | Thr | Threonine | L-Threonine |

Indication

When incorporated as an active ingredient in combination with other active components like fish oils, soya oil, and olive oil as a prescription medication (SMOFLIPID), medium chain triglycerides (MCTs) constitute a therapy indicated for supplying energy, calories, and essential fatty acids to adult patients, as part of a parenteral nutrition regimen, when oral or enteral nutrition is impossible, insufficient, or contraindicated [F126, F127]. However, given the predominant indication of MCTs for acting as a source of calories and essential fatty acids, the use of MCTs alone or as a component part of various unique, individual patient-tailored composite regimen therapies, MCTs are also ultimately indicated for a wide range of health conditions that involve energy deficiency, malnutrition, or disturbances in the ordinary absorption of dietary fats [A33175, F128]. Such conditions can include Crohn's disease, Waldmann disease, weight maintenance in AIDS, cachexia, and various disturbances in patient bile secretion (like cholestasis, disturbances in hepatic-intestinal circulation of bile acids, intestinal dysbacteriosis), or in pancreatic lipase secretion (like pancreatic failure in the course of cystic fibrosis) [A33175, F128].

Mechanism of Action

Absorption of larger long-chain triglycerides (LCT) requires specific processing in the digestive tract, like emulsification with bile [A33175]. This process is aimed at obtaining the maximum surface for digestion (lipolysis with breakage of ester bonds of triglycerides and with the release of monoglycerides, free fatty acids, and glycerol) [A33175]. The process of digestion of fats occurs largely in the duodenum and initial segment of the jejunum [A33175]. Lipases are found in the pancreatic juice and the brush border [A33175]. Once the aforementioned bonds are broken and the fatty acids and monoglycerides are absorbed into an enterocyte, they undergo resynthesis to triglycerides, in the presence of ligase, co-enzyme A, and ATP. Chylomicrons are formed. They get to the lymph and only then can they be transported to blood and destination organs [A33175]. Release of fats from chylomicrons requires the presence of plasmatic lipases, and only then can they be metabolised or stored as a reserve in the fatty tissue [A33175]. Conversely, hydrolysis of medium chain triglycerides (MCTs, which is faster than LCT hydrolysis anyway) does not require bile and lipase [A33175]. Without hydrolysis, they may also be absorbed by the enterocytes and they do not require re-esterification [A33175]. From enterocytes they are directly absorbed into the portal vein and then transported mainly to the liver. Thus, absorption of MCT is faster than that of LCTs [A33175]. Their metabolism is facilitated as well because they are metabolised by the liver almost completely (only when the liver’s metabolic abilities are exceeded the process is taken over by peripheral tissues) with energy release, regardless of the presence of carnitine (which is necessary for the transport of long-chain fatty acids through the mitochondrial membrane) [A33175]. Thanks to this the availability of medium-chain fatty acids for mitochondrial oxidation is better [A33175]. This means that MCT are an easy and quick source of energy [A33175]. However, it should be borne in mind that quantities of MCT exceeding the abilities of the liver are metabolised peripherally in a carnitine-dependent mechanism, which can increase the demand for it [A33175]. On the other hand, it has been observed that on the enterohormonal pathway (an important element of which is a MCT-induced increase of the YY peptide concentration and a decrease in cholecystokinin release) MCT cause a decrease of appetite and consequently a decrease in energy intake [A33175]. They also interfere with the metabolism of the fatty tissue, by hindering the creation of a deposit from long chain acids [A33175]. It has been proven that an MCT-enriched diet modulates metabolism of fats, which is manifested as a decrease in the concentration of triglycerides and cholesterol [A33175]. Moreover, unlike LCT, MCT do not affect the release of cholecystokinin or the emptying of the gallbladder and they do not increase the secretion of pancreatic enzymes [A33175]. They can speed up the intestinal passage by affecting the release of the YY peptide, but only in the distal sections of the intestine [A33175]. Moreover, it has been found that MCT facilitate absorption of calcium [A33175].

Pharmacokinetics

Absorption

The absorption of medium chain triglycerides is considered rapid [A33175, L2895, F126, F127, F128] but that both long-chain triglycerides and medium chain triglycerides share a similar absorption, which is an absorption rate of about 95% - similar to that of other ingested fats [L784].

Distribution

The apparent volumes of distribution have been researched as approximately 4.5 L for medium chain triglycerides and 19 L for medium chain fatty acids in a typical 70-kg subject [A33174].

Metabolism

In capillaries, both medium chain triglycerides (MCTs) and long-chain triglycerides (LCTs) are hydrolysed by lipoprotein lipase to glycerol and free fatty acids, and medium chain fatty acids (MCFAs) and long chain fatty acids (LCFAs), respectively [F126]. MCTs are hydrolysed at a faster rate than LCTs and therefore have a faster elimination rate [F126]. Free MCFAs then readily enter the liver, kidney, heart and other peripheral organs where they are oxidised by β-oxidation and the citric acid cycle to carbon dioxide and water [F126]. Alternatively, via the ketogenesis pathway, the β-oxidation of fatty acids generates the acetyl-CoA that can lead to the formation of ketone bodies like acetoacetate and β-hydroxybutyrate [F126].

Elimination

Clearance

The clearance of medium chain triglycerides in healthy control subjects was measured to be about 1.93 +/- 0.34 mL.kg-1.min-1 [A33179].

Toxicity

The excess use of medium chain triglycerides (MCTs) can lead to increased plasma levels of medium chain dicarboxylic acids, 3-hydroxy fatty acids and ketone bodies [F126]. Hyperketonaemia was observed in repeat-dose toxicity studies with SMOFLIPID [F126]. If excess MCTs are administered, the capacity of extrahepatic tissues to use ketone bodies is saturated and this may be of particular concern in some diabetes patients [F126]. The increased level of ketone bodies aggravates metabolic acidosis and accelerates the breakdown of homeostatic mechanisms [F126].

Active Ingredient/Synonyms

Caprylic/capric triglyceride | Caprylic/capric triglycerides | Coconut oil, fractioned | Fractionated coconut oil | Fractionated triglyceride of coconut oil | MCT | Medium chain triglyceride | Medium-chain glycerides | Triglycerides, medium-chain | Medium-chain triglycerides |

Indication

When incorporated as an active ingredient in combination with other active components like fish oils, soya oil, and olive oil as a prescription medication (SMOFLIPID), medium chain triglycerides (MCTs) constitute a therapy indicated for supplying energy, calories, and essential fatty acids to adult patients, as part of a parenteral nutrition regimen, when oral or enteral nutrition is impossible, insufficient, or contraindicated [F126, F127]. However, given the predominant indication of MCTs for acting as a source of calories and essential fatty acids, the use of MCTs alone or as a component part of various unique, individual patient-tailored composite regimen therapies, MCTs are also ultimately indicated for a wide range of health conditions that involve energy deficiency, malnutrition, or disturbances in the ordinary absorption of dietary fats [A33175, F128]. Such conditions can include Crohn's disease, Waldmann disease, weight maintenance in AIDS, cachexia, and various disturbances in patient bile secretion (like cholestasis, disturbances in hepatic-intestinal circulation of bile acids, intestinal dysbacteriosis), or in pancreatic lipase secretion (like pancreatic failure in the course of cystic fibrosis) [A33175, F128].

Mechanism of Action

Absorption of larger long-chain triglycerides (LCT) requires specific processing in the digestive tract, like emulsification with bile [A33175]. This process is aimed at obtaining the maximum surface for digestion (lipolysis with breakage of ester bonds of triglycerides and with the release of monoglycerides, free fatty acids, and glycerol) [A33175]. The process of digestion of fats occurs largely in the duodenum and initial segment of the jejunum [A33175]. Lipases are found in the pancreatic juice and the brush border [A33175]. Once the aforementioned bonds are broken and the fatty acids and monoglycerides are absorbed into an enterocyte, they undergo resynthesis to triglycerides, in the presence of ligase, co-enzyme A, and ATP. Chylomicrons are formed. They get to the lymph and only then can they be transported to blood and destination organs [A33175]. Release of fats from chylomicrons requires the presence of plasmatic lipases, and only then can they be metabolised or stored as a reserve in the fatty tissue [A33175]. Conversely, hydrolysis of medium chain triglycerides (MCTs, which is faster than LCT hydrolysis anyway) does not require bile and lipase [A33175]. Without hydrolysis, they may also be absorbed by the enterocytes and they do not require re-esterification [A33175]. From enterocytes they are directly absorbed into the portal vein and then transported mainly to the liver. Thus, absorption of MCT is faster than that of LCTs [A33175]. Their metabolism is facilitated as well because they are metabolised by the liver almost completely (only when the liver’s metabolic abilities are exceeded the process is taken over by peripheral tissues) with energy release, regardless of the presence of carnitine (which is necessary for the transport of long-chain fatty acids through the mitochondrial membrane) [A33175]. Thanks to this the availability of medium-chain fatty acids for mitochondrial oxidation is better [A33175]. This means that MCT are an easy and quick source of energy [A33175]. However, it should be borne in mind that quantities of MCT exceeding the abilities of the liver are metabolised peripherally in a carnitine-dependent mechanism, which can increase the demand for it [A33175]. On the other hand, it has been observed that on the enterohormonal pathway (an important element of which is a MCT-induced increase of the YY peptide concentration and a decrease in cholecystokinin release) MCT cause a decrease of appetite and consequently a decrease in energy intake [A33175]. They also interfere with the metabolism of the fatty tissue, by hindering the creation of a deposit from long chain acids [A33175]. It has been proven that an MCT-enriched diet modulates metabolism of fats, which is manifested as a decrease in the concentration of triglycerides and cholesterol [A33175]. Moreover, unlike LCT, MCT do not affect the release of cholecystokinin or the emptying of the gallbladder and they do not increase the secretion of pancreatic enzymes [A33175]. They can speed up the intestinal passage by affecting the release of the YY peptide, but only in the distal sections of the intestine [A33175]. Moreover, it has been found that MCT facilitate absorption of calcium [A33175].

Pharmacokinetics

Absorption

The absorption of medium chain triglycerides is considered rapid [A33175, L2895, F126, F127, F128] but that both long-chain triglycerides and medium chain triglycerides share a similar absorption, which is an absorption rate of about 95% - similar to that of other ingested fats [L784].

Distribution

The apparent volumes of distribution have been researched as approximately 4.5 L for medium chain triglycerides and 19 L for medium chain fatty acids in a typical 70-kg subject [A33174].

Metabolism

In capillaries, both medium chain triglycerides (MCTs) and long-chain triglycerides (LCTs) are hydrolysed by lipoprotein lipase to glycerol and free fatty acids, and medium chain fatty acids (MCFAs) and long chain fatty acids (LCFAs), respectively [F126]. MCTs are hydrolysed at a faster rate than LCTs and therefore have a faster elimination rate [F126]. Free MCFAs then readily enter the liver, kidney, heart and other peripheral organs where they are oxidised by β-oxidation and the citric acid cycle to carbon dioxide and water [F126]. Alternatively, via the ketogenesis pathway, the β-oxidation of fatty acids generates the acetyl-CoA that can lead to the formation of ketone bodies like acetoacetate and β-hydroxybutyrate [F126].

Elimination

Clearance

The clearance of medium chain triglycerides in healthy control subjects was measured to be about 1.93 +/- 0.34 mL.kg-1.min-1 [A33179].

Toxicity

The excess use of medium chain triglycerides (MCTs) can lead to increased plasma levels of medium chain dicarboxylic acids, 3-hydroxy fatty acids and ketone bodies [F126]. Hyperketonaemia was observed in repeat-dose toxicity studies with SMOFLIPID [F126]. If excess MCTs are administered, the capacity of extrahepatic tissues to use ketone bodies is saturated and this may be of particular concern in some diabetes patients [F126]. The increased level of ketone bodies aggravates metabolic acidosis and accelerates the breakdown of homeostatic mechanisms [F126].

Active Ingredient/Synonyms

Caprylic/capric triglyceride | Caprylic/capric triglycerides | Coconut oil, fractioned | Fractionated coconut oil | Fractionated triglyceride of coconut oil | MCT | Medium chain triglyceride | Medium-chain glycerides | Triglycerides, medium-chain | Medium-chain triglycerides |

Indication

Tryptophan may be useful in increasing serotonin production, promoting healthy sleep, managing depression by enhancing mental and emotional well-being, managing pain tolerance, and managing weight.

Mechanism of Action

A number of important side reactions occur during the catabolism of tryptophan on the pathway to acetoacetate. The first enzyme of the catabolic pathway is an iron porphyrin oxygenase that opens the indole ring. The latter enzyme is highly inducible, its concentration rising almost 10-fold on a diet high in tryptophan. Kynurenine is the first key branch point intermediate in the pathway. Kynurenine undergoes deamniation in a standard transamination reaction yielding kynurenic acid. Kynurenic acid and metabolites have been shown to act as antiexcitotoxics and anticonvulsives. A second side branch reaction produces anthranilic acid plus alanine. Another equivalent of alanine is produced further along the main catabolic pathway, and it is the production of these alanine residues that allows tryptophan to be classified among the glucogenic and ketogenic amino acids. The second important branch point converts kynurenine into 2-amino-3-carboxymuconic semialdehyde, which has two fates. The main flow of carbon elements from this intermediate is to glutarate. An important side reaction in liver is a transamination and several rearrangements to produce limited amounts of nicotinic acid, which leads to production of a small amount of NAD⁺ and NADP⁺.

Toxicity

Oral rat LD₅₀: > 16 gm/kg. Investigated as a tumorigen, mutagen, reproductive effector. Symptoms of overdose include agitation, confusion, diarrhea, fever, overactive reflexes, poor coordination, restlessness, shivering, sweating, talking or acting with excitement you cannot control, trembling or shaking, twitching, and vomiting.

Active Ingredient/Synonyms

(2S)-2-amino-3-(1H-indol-3-yl)propanoic acid | (S)-alpha-Amino-beta-(3-indolyl)-propionic acid | (S)-Tryptophan | (S)-α-amino-1H-indole-3-propanoic acid | L-(-)-Tryptophan | L-(−)-tryptophan | L-β-3-indolylalanine | Trp | Tryptophan | W | L-Tryptophan |

Indication

Promotes mental vigor, muscle coordination, and calm emotions. May also be of use in a minority of patients with hepatic encephalopathy and in some with phenylketonuria.

Mechanism of Action

(Applies to Valine, Leucine and Isoleucine)
This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet. The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with a-ketoglutarate as amine acceptor. As a result, three different a-keto acids are produced and are oxidized using a common branched-chain a-keto acid dehydrogenase, yielding the three different CoA derivatives. Subsequently the metabolic pathways diverge, producing many intermediates.
The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoA; thus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic.
There are a number of genetic diseases associated with faulty catabolism of the BCAAs. The most common defect is in the branched-chain a-keto acid dehydrogenase. Since there is only one dehydrogenase enzyme for all three amino acids, all three a-keto acids accumulate and are excreted in the urine. The disease is known as Maple syrup urine disease because of the characteristic odor of the urine in afflicted individuals. Mental retardation in these cases is extensive. Unfortunately, since these are essential amino acids, they cannot be heavily restricted in the diet; ultimately, the life of afflicted individuals is short and development is abnormal The main neurological problems are due to poor formation of myelin in the CNS.

Pharmacokinetics

Absorption

Absorbed from the small intestine by a sodium-dependent active-transport process.

Distribution

Metabolism

Hepatic

Elimination

Toxicity

Symptoms of hypoglycemia, increased mortality in ALS patients taking large doses of BCAAs.

Active Ingredient/Synonyms

(2S)-2-Amino-3-methylbutanoic acid | (S)-Valine | 2-Amino-3-methylbutyric acid | L-(+)-alpha-Aminoisovaleric acid | L-alpha-Amino-beta-methylbutyric acid | Val | Valine | L-Valine |