Ann N Y Acad Sci. 2004 Nov;1033:30-41.
Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism.
Rebouche CJ1.
Author information
Abstract
In mammals, the carnitine pool consists of nonesterified L-carnitine and many acylcarnitine esters. Of these esters, acetyl-L-carnitine is quantitatively and functionally the most significant.
Carnitine homeostasis is maintained by absorption from diet, a modest rate of synthesis, and efficient renal reabsorption. Dietary L-carnitine is absorbed by active and passive transfer across enterocyte membranes.
Bioavailability of dietary L-carnitine is 54-87% and is dependent on the amount of L-carnitine in the meal. Absorption of L-carnitine dietary supplements (0.5-6 g) is primarily passive; bioavailability is 14-18% of dose.
(Very interesting that oral absorption of the supplement form is so much lower which makes one wonder what in food allows the carnitine to be so well absorbed vs the supplement. I would love to see some research on this. Would taking supplemental carnitine with food high in carnitine increase the absorption? Can we isolate the food compound that is having the increasing action?)
Unabsorbed L-carnitine is mostly degraded by microorganisms in the large intestine. Circulating L-carnitine is distributed to two kinetically defined compartments: one large and slow-turnover (presumably muscle), and another relatively small and rapid-turnover (presumably liver, kidney, and other tissues).
At normal dietary L-carnitine intake, whole-body turnover time in humans is 38-119 h. In vitro experiments suggest that acetyl-L-carnitine is partially hydrolyzed in enterocytes during absorption. In vivo, circulating acetyl-L-carnitine concentration was increased 43% after oral acetyl-L-carnitine supplements of 2 g/day, indicating that acetyl-L-carnitine is absorbed at least partially without hydrolysis. After single-dose intravenous administration (0.5 g), acetyl-L-carnitine is rapidly, but not completely hydrolyzed, and acetyl-L-carnitine and L-carnitine concentrations return to baseline within 12 h.
At normal circulating l-carnitine concentrations, renal l-carnitine reabsorption is highly efficient (90-99% of filtered load; clearance, 1-3 mL/min), but displays saturation kinetics. Thus, as circulating L-carnitine concentration increases (as after high-dose intravenous or oral administration of L-carnitine), the efficiency of reabsorption decreases and clearance increases, resulting in rapid decline of circulating L-carnitine concentration to baseline. Elimination kinetics for acetyl-L-carnitine are similar to those for L-carnitine. There is evidence for renal tubular secretion of both L-carnitine and acetyl-L-carnitine. Future research should address the correlation of supplement dosage, changes and maintenance of tissue L-carnitine and acetyl-L-carnitine concentrations, and metabolic and functional changes and outcomes.
PMID: 15591001 DOI: 10.1196/annals.1320.003
https://www.ncbi.nlm.nih.gov/pubmed/15591001
So according to human pharmacokinetics, there is a ceiling somewhere with carnitine and when we reach it the body becomes less efficient at reabsorption and thus elimination increases. I have no idea where the ceiling is, and I suspect it is very high based on trusted folks here reporting positive effects up to 10ml/day aka Elvia, but at some point more is not better but that could be sky high amounts. Also increasing doses may increase excretion but perhaps we are still overcoming it with the exogenous usage.
As to the insulin driving carnitine into cells, I will be using Ecklonia Cava with Synthetine soon. Eclklonia cava is a seaweed that has strong antioxidant effects as well as promoting insulin release. The insulin release has only been studied thus far in human pancreatic cells and diabetic mice but anecdotal reports have many reporting strong BG lower properties and some are only able to take EC in the presence of carbohydrates. One user, in particular, is a diabetic and has been able to eliminate his Lantus and only uses his fast acting prior to meals, previously he was using both. Eliminating 30 units of Lantus a day is HUGE IMO.
From Examine:
In isolated pancreatic cells, 50ug/mL
Ecklonia Cava was able to augment glucose-induced insulin secretion by 2.8-fold[28] and
increased basal insulin has been found in diabetic mice (75%) with 3% Ecklonia in the feed with no significant influence on normal mice.[28] Increases to insulin secretion have been replicated in mice given 3-5% Ecklonia Cave.[30]
In instances of damage to the pancreatic cells, glucotoxicity (toxicity via excessive glucose) appears to be attenuated under the influence of Ecklonia extract; this particular study used an enzymatic hydrolysis of Ecklonia,[31] but a reduction of beta-cell losses during diabetes (experimental type II) has been noted with oral consumption of standard Ecklonia extract.[30]
https://examine.com/supplements/ecklonia-cava/#ref28
https://www.ncbi.nlm.nih.gov/pubmed/22645628
"CONCLUSION: These results suggest that EC play a role in controlling dietary glucose absorption at the intestine and
insulinotrophic action at the pancreas contributing blood glucose homeostasis in diabetic condition."
Combining Synthetine with some carbs and Ecklonia might be a nice stim free fat loss combo and overall performance enhancer. :headbang: