The Fat-Burning, Brain-Boosting Super-Molecule
It took two billion years of life on earth for our cells to work out a way to produce enough energy to get beyond being small, solo entities whose main goal was to replicate themselves. Energy is the very essence of life; from acquiring energy-providing molecules to breaking them down and harnessing that energy.
Our ancient single-celled ancestors learned how to do this alone, and only later figured out to co-operate in bigger and more complex structures. However, through the complexities of evolution and diversification as creatures filled up every niche on this great and diverse Earth, the basic underlying structures of energy production has not changed. It was perfected before diversification, and now we are stuck with that model, beautiful as it is.
Therefore, understanding these ancient systems is key to understanding how our bodies work, how they falter and what we can do to bring them back to running smoothly. This article is about L-carnitine and its role in getting fat, that clean burning high-octane fuel, to where it is needed. Then we will look at the role that a modified version of L-carnitine plays in certain diseases.
What is L-carnitine?
L-carnitine is an amino acid that plays an important role in metabolizing fat. Specifically, it acts as a carrier of long-chain fatty acids across the double membranes of the mitochondria. If you think of each cell as a city, the mitochondria are the city’s power plants. In this scenario, L-carnitine is like a tractor-trailer, carrying our densest fuel into the power plants.
The complex interplay of L-carnitine with two related membrane proteins provides the framework of a beautiful process that recycles L-carnitine after it has carried a molecule of fat across both mitochondrial membranes. One loads fat onto the carnitine carrier, the other unloads it on the other side.
The first of these proteins, Carnitine Acyltransferase I, connects a free-floating fatty acid to L-carnitine. This fat-carnitine complex moves through both mitochondrial membranes and into the core of the mitochondria where it meets up with a second membrane protein, Carnitine Acyltransferase II. This protein reverses the work of its outer membrane partner, splitting up the fatty acid and carnitine into their original structures.
Once inside both mitochondrial membranes, fatty acids are broken down to produce energy and L-carnitine is returned to collect more fats. Like a gondola carrying skiers up a mountain, L-carnitine leaves fats in their original state but in a new location before swinging back to pick up more.
Why do we need L-carnitine?
The carnitine shuttle is essential to protecting the mitochondria from the damage that could arise from a fat overload. Without a governor, fats might accumulate in the mitochondria faster than they could be metabolized, leaving them open for oxidation by reactive oxygen species (ROS). These oxidation reactions often start a cascade of harmful reactions that can lead to cell damage or even cell death. In fact, inadequately controlled propagation of oxidation reactions is a common feature of all mitochondrial-related diseases.
A deficiency in L-carnitine impairs the ability of cells to burn fat. Without a transporter, long-chain fatty acids cannot pass the energetic barrier keeping them out of the mitochondria. Instead, they can accumulate inside the cell, which can be damaging, or they are transported to and stored in adipose tissue, leading to undesirable weight gain. Alleviating this transporter deficiency promotes fat burning; providing a longer lasting cleaner energy source.
Fat is not the only macromolecule that is transformed into energy by the mitochondria, but it is the most energy dense. Fats provide 9 calories of energy per gram whereas sugar and protein provide just 4 calories per gram. This disparity explains why tissues like the brain, heart, and muscles thrive on fat as fuel. Their high-energy demand is more easily satisfied when it can use fat while storing sugar for more demanding times.
The benefits of switching to a fatty fuel aren’t just limited to the brain, heart, and muscles. Supplementing with carnitine is an effective method for improving sperm health and combating male infertility. A review of all the relevant literature concluded that pregnancy rate is significantly improved after L-carnitine or Acetyl-L-Carnitine (ALCAR) supplementation. Interestingly, taking carnitine increases the motility of sperm, but not their total number. With access to more fatty fuel, the sperm actually become more energetic, just like a swimmer supplementing with carnitines to improve endurance.
Are we deficient in L-carnitine?
L-carnitine is made in the liver and kidneys from the amino acids lysine and methionine. While there is a genetic mutation that impairs L-carnitine production in some people, this mutation is rare. It is therefore believed that L-carnitine deficiency is also rare, but as you will see this assumption has its flaws.
Our internal production of L-carnitine accounts for only 25% of the total body content, while the rest (100-300 mg/day) comes from our diet. Dietary carnitine comes predominantly from red meat, and to a lesser extent, chicken, fish, and milk products. A diet lacking red meat, which is becoming increasingly common, is therefore unlikely to provide sufficient dietary carnitine. In addition, a diet that is short on the L-carnitine building blocks lysine and methionine will impair our ability to maintain production in the liver.
Increasing consumption of processed and low-fat foods further increases the risk of L-carnitine deficiency and is supported by studies illustrating the benefits of L-carnitine supplementation. If supplementing L-carnitine or its related compounds is beneficial then it’s probably fair to assume that our diet is not providing enough for optimal health.
What is Acetyl-L-Carnitine (ALCAR)?
If you are already familiar with L-carnitine supplementation you may have also heard of other supplements bearing similar names, such as Acetyl-L-Carnitine (ALCAR), L-Carnitine-L-Tartrate (LCLT), and Propionyl-L-Carnitine (PLC). These variants all contain the same carnitine structure, but with additional appendages that modify its behavior in the body.
ALCAR, like L-carnitine, is produced in the body. In fact, these two species are converted back and forth in response to the body’s needs. Consequently, ALCAR provides the same fat-burning boost as L-carnitine. It also has a positive impact on the brain by improving memory and mood, while protecting against neurodegenerative disease – traits that may be attributed to ALCAR’s acetyl limb.
But what is an acetyl group?
Acetyl groups (CH3CO-) are small organic molecules that are present in every cell of the body. All our sources of energy – sugar, fat, and protein – are eventually broken down to acetyl groups on their path to producing ATP. Apart from their role in metabolism, they also influence the activity of other cellular structures.
Acetylation, the process of adding an acetyl group to another molecule, and its reverse process, de-acetylation, are one way in which cells modify the structure and activity of proteins – an on-off switch for regulating cell activities. Specifically, and important to this discussion, acetyl groups improve the ability of a substance to cross the blood-brain barrier and the gut wall - a characteristic commonly utilized when designing drugs. A prime example of this is acetylsalicylic acid, what we know as aspirin. The added acetyl group improves the absorption of salicylic acid through the gut and into the brain.
With an understanding of the role of acetyl groups, let's go back to ALCAR
This modified version of L-carnitine has a VIP pass to the brain – a privilege provided by the acetyl group. After passing the blood-brain barrier, ALCAR splits apart into L-carnitine and a free acetyl group. L-carnitine is then free to do its thing – shuttling fats into the mitochondria to be harvested for energy.
The fate of the acetyl group is a little more complicated. Research into the use of ALCAR for a number of diseases has shown that the acetyl group positively impacts the brain in a number of ways.
As it is an intermediate molecule in the energy production cycle, acetyl groups can enter the mitochondria when they are running low on fuel. ALCAR’s ability to alleviate chronic fatigue and ‘brain fog’ may be due, at least in part, to the availability of this partially processed fuel.
Synthesis of Acetylcholine (ACh)
ACh is an important neurotransmitter that is required for many cognitive functions in the brain. Some of these functions include attention, wakefulness, learning, and memory.
ALCAR’s rising popularity in the field of Nootropics (‘smart drugs’) is in part due to its ability to improve ACh levels in the brain. As we get older our neurons slow down their production of this critical neurotransmitter. By stimulating ACh production, ALCAR can improve cognition and slow down the cognitive decline that seemingly always accompanies aging.
In fact, it may be able to do more than just slow brain decline. In one study, in which older rats were given ALCAR along with the antioxidant alpha-lipoic acid, a significant improvement was observed in their memory, oxidative stress, and age-associated mitochondrial structure. Quite often, these old rats begin to biologically resemble their younger, healthier counterparts – an actual reversal in biological age!
ALCAR and Alzheimer’s Disease
Where a slow decline in ACh production occurs naturally as we age, a more significant and damaging drop-off is a common feature of Alzheimer’s disease. L-carnitine concentration in the brain also declines as this disease progresses.
With the ability to stimulate ACh production researchers have begun to investigate the therapeutic potential of ALCAR for Alzheimer’s. The early returns of this research are hard to decipher; some studies have shown significant improvements while others have shown little or no effect. A possible explanation for this pertains to the complexity of this disease and how far it has progressed in each individual. It may be that beyond a certain point ALCAR cannot repair the damage done by a substantial loss of ACh.
By preventing a decline in ACh concentration it’s more likely that ALCAR has a preventative effect on the occurrence and progression rather than the reversal of this disease. ALCAR’s well-documented ability to improve learning in studies on rats would appear to support this; stimulating the brain into action helps keep it in shape and safe from degradation. The phrase ‘use it or lose it’ aptly explains this phenomenon.
ALCAR, and plain old L-carnitine for that matter, may also assist in preventing Alzheimer’s the same way it helps with chronic fatigue – by increasing energy levels, leading to more exercise. The profound effect that exercise has on preventing Alzheimer’s is likely a secondary factor in explaining carnitine’s benefit to this disease.
Another way in which ALCAR acts on the brain is its ability to stimulate the production of neurotrophic factors. These are small proteins that protect our neurons by supporting their growth and survival.
Important neurotrophic factors, such as Brain-Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF), are lower in people with depression. Consistently, studies investigating the use of ALCAR as a potential antidepressant have shown improvements in patients’ depression scores after supplementing for 30-60 days – likely by increasing the levels of these crucial little molecules.
Even though it has proven effective, there is still a lack of studies comparing it to current antidepressants. The few studies that have been performed have found ALCAR to be equally effective and considerably safer than prescription alternatives. While more research is needed to validate these findings, the early indications demonstrate just another reason as to why ALCAR is so important to the brain.
Carnitine is an essential amino acid that, while made in the body, needs to be taken in through the diet or via supplements to achieve its full potential. These benefits include increased fat burning with less fatigue. Taking an ALCAR supplement provides the fat-burning effects of carnitine and positively impacts many functions of the brain. ALCAR is better absorbed from the gut and more able to reach the brain than simple L-carnitine.
There are a number of ways in which ALCAR improves brain function. In time these mechanisms will come to light and perhaps we will stop underestimating this powerful little molecule. Maybe all we need is a little more ALCAR in our diet to help us figure it out.
For more information on other methods and supplements that improve brain and mitochondrial function, read "Brain Health and Mitochondria - The Relationship Between Energy Production and Aging".
Mitochondria Balance contains 250mg of ALCAR per capsule (a very safe dose; only doses of 3000 mg or more have been shown to cause negative side effects like nausea and insomnia) along with other nutrients that synergistically work together to improve mitochondrial function and longevity.