Synthetine™ is an L-Carnitine based sterile preparation manufactured by a pharmaceutical company in accordance with the highest level of manufacturing practices. Synthetine is a highly bioavailable form of L-Carnitine that if used together with SyntheDextrin will activate a “switch” that will reduce carbohydrate oxidation and increases fat oxidation in contracting muscle, reduce fatigue, reduce muscle glycolysis and increase glycogen storage during periods that are almost always reserved for carbohydrate oxidation..

The science presented in this article is unique. It details a proven but little known protocol using Synthetine™ and SyntheDextrin™ that immediately enables the regulation of muscle fuel selection in favor of utilizing fats.

The focus of this article is an attempt to describe the science with enough detail so that the readers can incorporate this knowledge into their own plans to advance their fitness and health goals. This article is not about selling the aforementioned products. In the studies a highly bioavailable sterile L-Carnitine such as S ynthetine™ was used repeatedly together with either insulin or high glycemic shake such as SyntheDEXTRIN™ in the protocol that immediately activated the switch. However a second protocol is fully described herein and it involves low bioavailable oral ingestion of L-Carnitine and high glycemic shake. This second method is a slow build up process requiring daily use for 100 days to be fully active.

I make no apologies for the length of this article. I have kept the science understandable by introducing key concepts before explaining their specific relevance to the focus of this article. I have included a table of contents to make navigation easier.

During the 1990′s a substantial amount of research was undertaken which investigated the effects of L-carnitine supplementation on exercise performance. The primary hope of the research was that increasing carnitine availability in the body would lead to increased fat oxidation during prolonged exercise, spare glycogen stores and, consequently delay the onset of fatigue as well as promote fat loss. Scientific interest in L-carnitine as a performance enhancement and weight loss tool came to an end when it became apparent that L-carnitine feeding does not alter fuel metabolism during exercise or, more importantly impact upon the muscle carnitine pool in humans.

The scientific community for the most part abandoned further research. L-carnitine’s metabolic role had been thoroughly mapped out and described in the literature. The typical carnivorous diet seemed to supply sufficient carnitine. Carnitine supplementation proved to be of no additional benefit…it was simply excreted… end of story.

Despite the failure of science, L-carnitine feeding as a tool to promote weight loss and improve exercise performance became a multimillion dollar dietary supplement industry with no genuine benefit to the end users.

Today our understanding of the transport mechanisms that permit cellular membrane penetration are much more advanced. What was once a saturated transporter and an impermeable membrane are now elements that are open to favorable manipulation, sometimes in surprisingly simple and physiologically obtainable ways. The hopes and hypes of yesterday with the scientific approaches described herein are reborn anew.

Synopsis
This article summarizes in understandable language the elements of metabolism that are necessary to appreciate both the mechanisms and conclusions arrived at through a series of studies published in very well respected journals by a group of scientists I’ll label the “Stephens Group”. The group of four scientists, headquartered at the “Centre for Integrated Systems Biology and Medicine” at Queen’s Medical Centre, University of Nottingham in the United Kingdom examined carnitine’s importance as a regulator of skeletal muscle fuel selection.

They came to the understanding that because carnitine is vitally involved in both fat metabolism and carbohydrate metabolism in the cellular mitochondria (where energy production takes place) and because the pool of available carnitine is restricted at that level, carnitine availability is “the switch” that toggles between these two systems for energy creation.

There are periods of times when the use of glucose (derive from carbohydrates) as a fuel increases. This occurs at high intensity exercise and when there is plenty of glucose available. When this occurs this metabolic pathway calls upon carnitine within the mitochondria for use in the process and this takes away from the carnitine that is available for fat metabolism. This results in a “switch away” from the use of fats for fuel in favor of glucose.

The Stephens Group was able to fully describe this process and discover that there exists a “switch back” which reduces glucose metabolism and increases fat metabolism even during those periods of time (high intensity exercise, carbohydrate intake and preference for glycolysis) that normally demand otherwise.

In essence they discovered that increasing skeletal muscle carnitine above a threshold inhibited carbohydrate oxidation.

They then moved forward and also discovered that increasing skeletal muscle carnitine above a threshold also increased fat oxidation.

Having identified this “switching mechanism” they then discovered that increasing muscle carnitine content in healthy humans at rest reduced glycolysis, increased glycogen storage and increased fat oxidation.

They then came to the understanding that increasing muscle carnitine content alleviated the decline in fat oxidation rates during high intensity exercise and reduced muscle glycogen utilization. They were able to reference in vitro (out of body) studies that reported that increasing muscle carnitine substantially delayed the onset of fatigue.

Having established the “switching” mechanism and its potential positive benefits they then set about discovering a method for increasing carnitine in muscle. It is important to remember that this had never been accomplished before.

Their studies discovered two protocols. One protocol resulted in an immediate and rapid increase in muscle carnitine levels to the switching threshold. This protocol involved a highly bioavailable method that increased the influx of carnitine into muscle cells. The second protocol involved a slower day to day build up of carnitine levels and took 100 days to arrive at the switching threshold. This protocol involved lower bioavailability but more convenient methods.

The first protocol might be considered by bodybuilders, athletes and fitness enthusiasts while the second might be better suited for the public at large.

Introduction to Fat Oxidation
To sustain life the production of energy is required. This process necessitates the acquisition & concurrent use of both oxygen and a fuel source. Fuel sources are available from either consumption of carbohydrates, fats, and rarely proteins or the release of stored fuels from within the body. The ingestion of dietary fat is an initial energy acquisition process called consumption while the process called oxidation is the final step of conversion into human energy. Between the initial process of consumption and the final step of conversion are the processes of storage and eventual release for conversion into energy.

Whether the middle processes of fat storage or fat release are activated depends primarily on the state of energy balance at any point in time. If there is a surplus of fuel sources from ingested carbohydrates or fats then fat will not be released from storage in fat cells in appreciable quantities and the body will use its preferred source of energy carbohydrates followed by newly ingested fats to meet its energy requirements.

When there is a surplus of energy from consumption (i.e. eating outpaces physical activity) the human body will not readily convert excess carbohydrates into fat stores but will use them for energy. Carbohydrate ingestion does not always lead to increased fat stores but may do so by being excessive and by crowding out concurrently ingested fats’ potential to be utilized as energy. As a result ingested fats during periods of surplus energy consumption will generally be stored in fat cells.

Ingested fats are broken down and converted into free fatty acids, which are then stored in fat cells in a form known as triglycerides where they remain as potential energy units until called for by negative energy states.

When energy balance is in a deficit (i.e. physical activity outpaces eating) fat oxidation will increase. In order for this final step of oxidative conversion into human energy to occur the middle step of release of fat stores (triglycerides) must take place. This process will result in loss of fat mass.

Various hormones will trigger the release of the triglycerides from fat cells. These triglycerides, through a process labeled lipolysis are broken down into two compounds and released into the bloodstream. The first compound glycerol is primarily converted to glucose by the liver and provides energy for cellular metabolism. The second compound fatty acids are transported to the mitochondria, the portion of a cell that produces energy within each cell.

This is the stage where carnitine plays an essential role in fatty acid oxidation. It is not possible for the newly liberated fatty acids to penetrate the mitochondria membrane and enter the mitochondria without the help of carnitine which acts as a transport mechanism.

In general, carnitine transports long-chain acyl groups from fatty acids into the mitochondria where they are broken down through beta-oxidation in a process that ends up creating adenosine triphosphate (ATP), the energy-producing fuel.

The research studies have examined the possibility that greater amounts of fatty acids could be oxidized if carnitine levels were elevated through supplements. Carnitine increases via supplementation were determined to have no effect on fatty acid oxidization.

It is important to note that what I have described concerning energy balance and fat storage versus release is a generalized net (or overall) effect. Fat is constantly being stored in and released from fat cells no matter what the current energy state however the overall net effect very much depends on the state of energy balance, or as is the focus of this paper L-carnitine can be made to oxidize fat even in the presence of a positive energy balance.

Summary of the two roles played by Carnitine
In order to understand the relevant conclusions drawn from the Stephens Group’s research detailed from their studies herein it is necessary to understand a few elementary essentials concerning carnitine’s role in skeletal muscle fuel metabolism and briefly mention the “competing” metabolic pathway and a second function of carnitine, which is to act as a buffer during carbohydrate metabolism. When free carnitine is engaged in its role as a buffering agent for carbohydrate metabolism long-chain fatty acid oxidation diminishes.

Role 1: Energy Pathway “Fatty acid transport/oxidation” – Two pools of carnitine transport
The Mitochondria (the intra-cellular area where oxidation and energy production occurs) membrane is impermeable to fatty acyl-CoA (i.e. the long-chain fatty acid liberated from fat cells bonded to an enzyme named coenzyme A (CoA).) But this is not true if it is bound to carnitine. Carnitine enables the fatty acid to penetrate the membrane and it does so by binding to it and forming acylcarnitine.

However there are two separate pools of carnitine that need to be utilized to move fatty acids into the mitochondria. One pool located outside of the mitochondria membrane and one pool located inside the mitochondria matrix. The one outside the mitochondria is the one that binds to fatty acids and transports them through the first of 2 layers that make up the membrane and up to the 2nd inner layer but not through the mitochondria membrane. The pool of carnitine inside the mitochondria is known as “intra-mitochondria free carnitine”. It moves to the membrane from the inside and is “handed” the fatty acyl-CoA that was delivered “to the door” by outside carnitine. The handing over process is mediated by an enzyme called Carnitine palmitoyltransferase I (CPT1) which resides on the 2nd layer of the membrane. We don’t need to introduce all the various proteins and enzymes involved in the process. Simply understand that CPT1 is akin to a bouncer at a nightclub who takes a note from someone outside the doorway and gives it to someone inside the doorway.

In this way two carnitines (one from outside & one from inside the mitochondria) do the work of transporting the fatty acyl-CoA.

Inside the mitochondria matrix the newly formed acylcarnitine (thanks to the hand off) is reduced back to two individual components: free carnitine and the long chain fatty acyl-CoA.