The energetic outcomes from mitochondrial fat oxidation, is the ultimate measure of 'how efficient' a metabolism is. However, there are prior steps of mitochondrial fatty acid transport that can materially effect 'efficiency'.
While science has understood for years the biochemical role that the amino acid Carnitine played in long-chain fatty acid transport - it was only in 2011(3) that research showed, how muscle-carnitine levels could be increased (21%).
Most interesting to the 2011 paper, was the impact of raised muscle-carnitine levels, notably, 55% less glycogen use at lower (aerobic) intensities, PDC activation increased by 38% and lactate content lower by 44% - all leading to a 11% higher work output in a performance trial.
While the approach in the research was self-recognized by researchers as not overly practical, it opened insight for further investigation.
We know that both the heart and skeletal muscle tissue use both long-chain, and medium-chain fatty acids as key substrate-fuels. This is certainly the case at aerobic intensities, while some research (5, 6) would suggest that through intervention, beta-oxidation can further continue at high-intensities also.
In the case of long-chain fatty acids, it has long been understood that both oxidation processes and membrane transport are Carnitine dependent. Contrary to this, it has been thought that medium-chain fatty acids can traverse cellular membranes in the heart, liver, kidney and skeletal muscle independent of carnitine supported transporters and/or enzymes.
However, in a recent (7) paper it was found that medium-chain triglycerides can traverse cell membranes in some tissues, namely the liver, where as for heart and skeletal muscle, Medium-chain fatty acids traverse membranes in a Carnitine dependent way also (like long-chain fats).
What is further interesting in this paper, is how the body endogenously generates medium-chain fatty acids namely C8 through peroxisomal oxidation of long-chain fatty acids. Then through the help of carnitine, the medium-chain fatty acid is then transported into the mitochondria as substrate for energy production.
ANTAGONIST TO FATTY-ACID OXIDATION
Counter to improving efficiency, it's important to highlight factors which can antagonize fatty-acid oxidation and mitochondrial efficiency - namely Fructose.Various studies (8, 9) have shown the metabolic effects of fructose intake on reducing fatty-acid oxidation, and mitochondrial function - both in liver and skeletal muscle tissue. Other studies (10, 11) highlight how fructose diet both raised liver fat-accumulation, while having a depleting effect of muscle and liver glycogen. Interesting, that in these same studies, the fructose triggered abnormities could be bought back to normal levels, when supplemented with Carnitine.
PRACTICAL APPLICATION FOR ENDURANCE PERFORMANCE
Research is becoming increasingly suggestive that raising Carnitine levels in skeletal muscle is not only possible, but can support material metabolic improvements that are highly relevant to endurance performance - namely,- greater use of long/medium chain fatty acids as substrate-fuel for aerobic and likely even higher intensities,
- at lower-intensities, glycogen can be spared, and at higher-intensities lactate production can be lowered,
Read on to PART 2 of CARNITINE, and the recent studies on how to optimize muscle loading to realize the advantages in endurance performance.
REFERENCES
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Maximal Fat Oxidation is Related to Performance in an Ironman Triathlon. Frandsen J et al. International journal of sport medicine. Nov 2017
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Metabolic Signatures of Performance in Elite World Tour Professional Male Cyclists. Nemkov T et al. Sports Medicine. Aug 2023.
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Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. Wall. B et al. Sports Medicine. Journal of Physiology Feb 2011
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Caffeine ingestion stimulates plasma carnitine clearance in humans. Wall B et al. Physiological Reports. Feb 2023.
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Priority use of medium-chain fatty acids during high-intensity exercise in cross country skiers. Lyudinina A et al. Journal of the International Society of Sports Nutrition. Dec 2018
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Low and high carbohydrate isocaloric diets on performance, fat oxidation, glucose and cardiometabolic health in middle age males. Prins P et al. Frontiers in Nutrition. Feb 2023
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Medium-chain fatty acid oxidation is independent of l-carnitine in liver and kidney but not in heart and skeletal muscle. Pereyra A et al. American Journal of Physiology Gastrointestinal Liver Physiology. Oct 2023
- Fructose impairs fat oxidation: Implications for the mechanism of western diet-induced NAFLD. Mustafa K et al. The Journal of Nutritional Biochemistry. Apr 2023
- Fructose induces mitochondrial dysfunction and triggers apoptosis in skeletal muscle cells by provoking oxidative stress. Jaiswal N et al. Apoptosis. Jul 2015
- Fructose-induced hepatic gluconeogenesis: effect of L-carnitine. Rajasekar P et al. Life Sciences. Mar 2007
- L-Carnitine counteracts in vitro fructose-induced hepatic steatosis through targeting oxidative stress markers. Montesano A et al. Journal of Endocrinological Investigation. Apr 2020
