Ayiram

Uses

Choline is a nutrient found in a wide variety of vitamins including pre-natal formulations.

For nutritional supplementation, also for treating dietary shortage or imbalance

The supplemental Levocarnitine use is widely established in the management of cardiac ischemia and peripheral arterial disease. It is generally used for cardio protection. It lowers triglyceride levels and increases levels of HDL cholesterol. It is used with benefits in those with primary and secondary carnitine deficiency syndromes. There is also evidence of its use in liver, kidney and immune disorders or in diabetes and Alzheimer's disease. There is little evidence that supplemental Levocarnitine boosts energy, increases athletic performance or inhibits obesity. The indications of Levocarnitine may be summarized as follows:

• Heart Diseases
• Congestive Heart Failure
• Kidney Disease
• Chronic Fatigue Syndrome
• High Cholesterol
• Intermittent Claudication
• Dementia and memory impairment
• Down Syndrome
• Male infertility
• Hyperthyroidism

Selenium is an ingredient found in a variety of supplements and vitamins.

For the supplementation of total parenteral nutrition to prevent hyposelenemia .

Ayiram is also used to associated treatment for these conditions: Nutritional supplementationCarnitine Deficiency, Congenital carnitine deficiency, Secondary Carnitine deficiencyNutritional supplementation

How Ayiram works

Choline is a major part of the polar head group of phosphatidylcholine. Phosphatidylcholine's role in the maintenance of cell membrane integrity is vital to all of the basic biological processes: information flow, intracellular communication and bioenergetics. Inadequate choline intake would negatively affect all these processes. Choline is also a major part of another membrane phospholipid, sphingomyelin, also important for the maintenance of cell structure and function. It is noteworthy and not surprising that choline deficiency in cell culture causes apoptosis or programmed cell death. This appears to be due to abnormalities in cell membrane phosphatidylcholine content and an increase in ceramide, a precursor, as well as a metabolite, of sphingomyelin. Ceramide accumulation, which is caused by choline deficiency, appears to activate Caspase, a type of enzyme that mediates apoptosis. Betaine or trimethylglycine is derived from choline via an oxidation reaction. Betaine is one of the factors that maintains low levels of homocysteine by resynthesizing L-methionine from homocysteine. Elevated homocysteine levels are a significant risk factor for atherosclerosis, as well as other cardiovascular and neurological disorders. Acetylcholine is one of the major neurotransmitters and requires choline for its synthesis. Adequate acetylcholine levels in the brain are believed to be protective against certain types of dementia, including Alzheimer's disease.

Levocarnitine can be synthesised within the body from the amino acids lysine or methionine. Vitamin C (ascorbic acid) is essential to the synthesis of carnitine. Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. Levocarnitine is handled by several proteins in different pathways including carnitine transporters, carnitine translocases, carnitine acetyltransferases and carnitine palmitoyltransferases.

Selenium is first metabolized to selenophosphate and selenocysteine. Selenium incorporation is genetically encoded through the RNA sequence UGA . This sequence is recognized by RNA ste loop structures called selenocysteine inserting sequences (SECIS). These structures require the binding of SECIS binding proteins (SBP-2) to recognize selenocystiene. The specialized tRNA is first bound to a serine residue which is then enzymatically processed to a selylcysteyl-tRNA by selenocystiene sythase using selenophosphate as a selenium donor. Other unidentified proteins are required as part of the binding of this tRNA to the ribosome. Selenoproteins appear to be necessary for life as mice with the specialized tRNA gene knocked out exhibited early embryonic lethality .

The most important selenoproteins seem to be the glutathione peroxidases and thioredoxin reductases which are part of the body's defenses againts reactive oxygen species (ROS) . The importance of selenium in these anti-oxidant proteins has been implicated in the reduction of atherosclerosis by preventing the oxidation of low density lipoprotein . Selenium supplementation is also being investigated in the prevention of cancer and has been suggested to be beneficial to immune function .

Dosage

Ayiram dosage

Tablet-

• Adults: The recommended oral dosage for adults is 990 mg, two or three times a day using the 330 mg tablets, depending on clinical response.
• Infants and children: The recommended oral dosage for infants and children is between 50 and 100 mg/kg/day in divided doses, with a maximum of 3 g/day. Dosage should begin at 50 mg/kg/day. The exact dosage will depend on clinical response.

Monitoring should include periodic blood chemistries, vital signs, plasma carnitine concentrations and overall clinical condition.Syrup-

• Adults: 10 to 30 ml/day. Dosage should start at 10 ml/day in divided doses, and be increased slowly while assessing tolerance and therapeutic response.
• Infants and children: 50 to 100 mg/kg/day which is equivalent to 0.5 ml/kg/day. Dosage should start at 50 mg/kg/day, and be increased slowly to a maximum of 3 g/day (30 ml/day) while assessing tolerance and therapeutic response. Solution may be consumed alone or dissolved in drink or other liquid food. Doses should be spaced evenly throughout the day (every three or four hours) preferably during or following meals and should be consumed slowly in order to maximize tolerance.

Side Effects

Generally Levocarnitine is well tolerated. However, few side effects including transient nausea and vomiting, abdominal cramps, and diarrhoea may occur

Toxicity

Oral rat LD₅₀: 3400 mg/kg

LD₅₀ > 8g/kg (mouse, oral). Adverse effects include hypertension, fever, tachycardia and seizures.

Oral LD50 of 6700mg/kg in rats . Selenium exposure is teratogenic and can result in fetal death as tested in mice. Chronic toxicity is characterized by hair loss, white horizontal streaking on fingernails, paronchyia, fatigue, irritability, hyperreflexia, nausea, vomiting, garlic odor on breath, and metallic taste . Serum selenium correlates weakly with symtoms. Blood chemistry as well as liver and kidney function are normally unnaffected. Acute toxicity presents as stupor, respiratory depression, and hypotension. ST elevations and t-wave changes characteristic of myocardial infarction may be observed.

Precaution

The safety and efficacy of oral Levocarnitine has not been evaluated in patients with renal insufficiency. Chronic administration of high doses of oral Levocarnitine in patients with severely compromised renal function or in ESRD patients on dialysis may result in accumulation of the potentially toxic metabolites, trimethylamine (TMA) and trimethylamine-N-oxide (TMAO), since these metabolites are normally excreted in the urine

Interaction

Reports of INR increase with the use of warfarin have been observed. It is recommended that INR levels be monitored in patients on warfarin therapy after the initiation of treatment with levocarnitine or after dose adjustments.

Volume of Distribution

The steady state volume of distribution (Vss) of an intravenously administered dose, above endogenous baseline levels, was calculated to be 29.0 +/- 7.1L. However this value is predicted to be an underestimate of the true Vss.

Elimination Route

Absolute bioavailability is 15% (tablets or solution). Time to maximum plasma concentration was found to be 3.3 hours.

Oral bioavailability of 90% when given as L-selenomethionine . Tmax of 9.17h.

Half Life

17.4 hours (elimination) following a single intravenous dose.

Half life was observed to increase with chronic dosing time . For day 1-2 half life was 1.7 days. For day 2-3 half life was 3 days. For day 3-14 half life was 11.1 days.

Clearance

Total body clearance was found to be a mean of 4L/h.

Elimination Route

Following a single intravenous dose, 73.1 +/- 16% of the dose was excreted in the urine during the 0-24 hour interval. Post administration of oral carnitine supplements, in addition to a high carnitine diet, 58-65% of the administered radioactive dose was recovered from urine and feces in 5-11 days.

Mainly excreted in urine as 1beta-methylseleno-N-acetyl-d-galactosamine and trimethylselenonium . The amount excreted as 1beta-methylseleno-N-acetyl-d-galactosamine plateaus at doses around 2microg after which the amount excreted as trimethylselenonium increases. Some selenium is also excreted in feces when given orally .

Pregnancy & Breastfeeding use

Levocarnitine is categorized by the USFDA as Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. Supplemental Levocarnitine should be used by pregnant women only if clearly indicated and only under medical supervision. It is not known whether Levocarnitine is excreted in human milk. Supplemental Levocarnitine is not advised for nursing mothers. Those with seizure disorders should only use Levocarnitine under medical advisement and supervision.

Contraindication

There is no known disease or syndrome in which Levocarnitine administration is contraindicated. It is contraindicated in patients with hypersensitivity to any of its components.

Acute Overdose

There have been no reports of toxicity from levocarnitine overdosage. Levocarnitine is easily removed from plasma by dialysis. The intravenous LD50 of levocarnitine in rats is 5.4 g/kg and the oral LD50 of levocarnitine in mice is 19.2 g/kg. Large doses of levocarnitine may cause diarrhea.

Storage Condition

Tablet: Store in a cool & dry place, protected from light & moisture.

Solution: Store in a cool & dry place, protected from light.

Innovators Monograph

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