Thursday, July 4, 2013

Carnitine Loading Revisited: 3g Carnitine per Day Ward Off Vitargo Induced Fat Gain by Increasing Fatty Acid Oxidation and Total Energy Expenditure in 12 Week Human Study

Figure 1: With highly bioavailable carnitine in meat it is 100% paleo (unlike coke, obviously ;-)
I am not sure, whether its ten, twenty or maybe two-hundred ;-) years ago that the first carnitine supplement was introduced to the sport supplement market (from a paleo perspective it has always been there - in the form of meat!); and honestly I am too lazy to google it up. What I do know, however is that carnitine has been around ever since I first started working out. Incidentally, the same can be said about the debate whether or not supplementing with one or another form of this endogenously synthesized amino acid (your body can make carnitine from the amino acids lysine and methionine) would actually or just theoretically be beneficial for the average trainee.

Years have passed and I still hesitate, whenever someone asks me whether or not I'd recommend trying this or that form of l-carnitine to increase his or her performance. After years of being inclined to answer: "Very unlikely." The publication of a handful of promising studies over the past months makes me question, whether "May be worth a try" would not be a more appropriate response to this sixty-four-thousand dollar question.

Sixty-four-thousand dollars for l-carnitine?

The most recent of these studies is going to be published in the Journal of Physiology in a couple of weeks. It was conducted by researchers from the MRC/Arthritis Research UK Centre for Musculoskeletal Ageing Research, School of Biomedical Sciences at the University of Nottingham in the UK, and investigated the effects the provision of 2x1.36g of carnitine per day had on the energy
metabolism, body fat mass, and muscle expression of fuel metabolism genes.responses of 12 men who exercised at 50% VO2max for 30 min once before and once after 12 weeks twice daily feeding of
  • 80 g carbohydrate from Vitargo (Control, n=6) or 
  • 1.36 g L-carnitine + 80 g carbohydrate (Carnitine, n=6). Maximal
Contrary to what you may expect, the activity of the "fatty acid carnitine shuttle" or rather the corresponding mitochondrial enzyme, namely carnitine palmitolytransferase 1 (CPT1) remained similar in both groups over the course of the 12-week study period.

Suggested read: "Meaty "News": Choline, Carnitine & "Bacteria Poop" Make (Red) Meat Unhealthy. Learn Why the Latest Revelations Are Neither New, Nor Meat-Specific And Still Made the News" (read more)
Still, the additional carnitine did prevent the statistically significant weight and fat gain (1.9kg and 1.8kg, respectively) the scientists observed in the the control group. It also ...
  • increased the muscle total carnitine concentration by +20%
  • ramped up the activity of long-chain acyl-CoA, an enzyme that is crucially involved in the mitochondrial oxidation of long-chain fatty acids by +200% and
  • upped the whole body energy expenditure by a comparatively small, but statistically significant +5%
Moroever, the researchers found 73 out of 187 genes relating to fuel metabolism to be upregulated in the subjects who had been randomized to the active arm of the study.

What mechanisms are at work and what do they do?

Now it is unquestionably not straight forward how these results relate to the one and only practically relevant outcome of the study - the lack of weight gain. Therefore it does appear prudent to take a look at what the researchers say about the relationship between the total carnitine levels, the expression of long-chain acyl-coa and the overall increase in energy expenditure on the decreased weight gain.

Their reasoning that the"20% increase in muscle carnitine content prevented the 1.8 kg increase in body fat mass associated with daily ingestion of a high carbohydrate beverage." Does yet not have large explanatory power imho. If the participants had been following a regular workout routine and the whole body energy expenditure hat been increased in all of these sessions to the same degree it was in the post-intervention test (+5%), this would probably make sense.

Table 1: Amount of carnitine in selected foods (learn more)
If we take a look at the other parameters the scientists measured, it is likely, yet by no means dead certain that this increase took place. After all, the changes in energy expenditure  were accompanied by...
"[...] an increase in fat oxidation, and a marked adaptive increase in the expression of gene networks involved in insulin signalling, peroxisome proliferator activated receptor (PPAR) signalling, and fatty acid metabolism over and above the decline observed in Control." (Stephens. 2013)
If we do assume that exercise does not thwart (maybe even promote) these effects, it could thus in fact make sense to answer the sixty-four-thousand dollar question by stating that it may at least be worth a try for those with unlimited funds.

And that despite the fact that the "mechanism underlying the increase in energy expenditure is not entirely clear" (Stephens, 2013) and the researchers can only speculate that it may be the result of carnitine driven increases in the rate of fac oxidation.
"Muscle free carnitine content was not measured after 20 min of exercise in the present study, but in our previous study (Wall. 2011) a 20% increase in skeletal muscle total carnitine content following 24 weeks of daily L-carnitine and carbohydrate feeding resulted in a striking 80% greater availability of muscle free carnitine following 30 min of low intensity exercise compared to Control, which was associated with a 30% reduction in PDC [pyruvate dehydrogenase complex] activation and 55% reduction in muscle glycogen utilisation." (Stephens. 2013)
For these changes to become practically relevant they would yet, as Stephens et al, suggest have to be present at reast, And while the 4-fold increase in resting muscle long-chain acyl-CoA content, of which the authors have shown previously (Stephens. 2006) to be consistent with an increase in muscle carnitine content and a switch in fuel metabolism at rest, would suggest that this is the case, I am not yet inclined to back off of my "probably not worth the extra bucks".

Carnitine may also ramp up anabolic and shut down catabolic signals in trainees and I'd say this is probably a better argument to supplement than the "anti-cok(e)obesity effect" (learn more)
Bottom line: Despite the accumulating evidence of real world benefits of carnitine supplementation it would be cheaper and way easier to simply not guzzle an additional 4x servings of coke a day if you want to avoid weight gain.

And if you are really looking for arguments in favor of carnitine supplementation I'd suggest you'd rather base your decision to invest into a bag of bulk l-carnitine on the IGF-1, p-AKT and mTOR boosting and and atrogin, murf and fox-o inhibiting anabolic and anti-catabolic effects study by Keller et al. reported in their March 2013 study you've read about here at the SuppVersity on March 18, 2013 (read more).

References:
  • Keller J, Couturie A, Haferkamp M, Most E, Eder K. Supplementation of carnitine leads to an activation of the IGF-1/PI3K/Akt signalling pathway and down regulates the E3 ligase MuRF1 in skeletal muscle of rats. Nutrition & Metabolism. 2013; 10:28 
  • Stephens FB, Wall BT, Marimuthu K, Shannon CE, Constantin-Teodosiu D, Macdonald IA, Greenhaff PL. Skeletal muscle carnitine loading increases energy expenditure, modulates fuel metabolism gene networks, and prevents body fat accumulation in humans. J Physiol. 2013 Jul 1. [Epub ahead of print]
  • Wall BT, Stephens FB, Constantin-Teodosiu D, Marimuthu K, Macdonald IA, Greenhaff PL.
    Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. J Physiol 2011. 589:963-973.