Forgotten Dieting Aids: Choline, Carnitine, Caffeine and the Anti-Weight-Loss Plateau Effects of Sugar and Phosphates

I bet both Flex Wheeler (left) as well as Serge Nubret (right) still knew what choline is. Something you probably cannot say of many of today's gymrats.
In view of the fact that the brief "Oldie but Goldie" post on the efficiency of a stack of carnitine, choline and caffeine as a weight loss adjuvant on the SuppVersity Facebook Wall caught so much attention, I thought that especially those of you who have not yet "liked" the SuppVersity on Facebook and have thus missed this brief reminder of these "classic" fat loss helpers would appreciate if I devote a whole post to this issue as well as another "Oldie but Goldie", I came across recently: The anti-plateau effects of succrose (plain sugar) and phosphates during phases of (very) intense dieting.

ECA was yesterday and so was CCC ;-) 

Let's start with the CCC stack, though. In the year 2000, Hongu et al. published a paper describing a rodent experiment in which they were able to show that the combination of choline, carnitine and caffeine had similar beneficial effects on the body fat and leptin levels of sedentary rodents as exercise (Hongu. 2000).
Figure 1: Fat pad weight (in g) and serum glucose, lactate, triglycerides, free fatty acids and leptin levels expressed relative to sedentary rodents on standard chow (Hongu. 2000)
With statistically highly significant reductions in the weight of the epididymal, inguinal and perirenal fat tissue and corresponding decreases in leptin, the net fat (not simply weight!) loss the 7-wk-old male Sprague-Dawley rats exhibited in face of an unaltered basal energy intake at the end of the 5-weeks study period was yet so pronounced that the question, whether these results would be replicable and, more importantly, whether they could be reproduced in human beings should already be preying on your mind.

"So you are saying it's unlikely this will work in humans, right?"

For a follow up study, the scientists recruited 19 healthy non-obese women with no history of diabetes, or cardiovascular disease (18–54y; body weight, 47.5–92.7 kg; body mass index (BMI), 18.9–35.9kg/m²; body fat, 17.9–37.8%) and repeated the experiment (Hongu. 2003); yet with a slightly different design (see figure 2) that would allow the researchers to differentiate the individual effects of choline and carnitine - unfortunately, without the third "C", i.e. the caffeine.
Figure 2: Study design of the follow up human study three years later (Hongu. 2003).
In the absence of caffeine, the combination of choline and carnitine lost its congenial partner in crime, whose job it is to squeeze the lipids out of the fat cells (lipolysis). But that's not all, the dosages used in the human trial were also significantly lower than the human equivalents of those the rodents had coonsumed three years before (see infobox to the right of the next paragraph). With appropriately high doses, the caffeine may even not have been necessary to elicit the desired fat loss effects. What is unquestionable though is thatthe caffeine induced lipolysis would have amplified any existing effect, because you obviously need enough fatty acids to be transported to the mitochondria in order to make optimal use of the increase in oxidative capacity from the other "C"s in the CCC stack.

What we have here is not a fat loss study

What were the dosages of choline, carnitine and caffeine that were used in the studies? The human equivalent doses for the rodent study from 2000 were 98mg/kg choline, 52mg/kg carnitine and 1mg/kg caffeine. In the human study from 2003 the scientists used much lower dosages of 15mg/kg choline bitartrate and only 1mg/kg l-carnitine l-tartrate per day (!) no wonder the effects on the body composition were completely absent in the human trial.
Against that background the results of this follow up study are of greater theoretical than practical value for us, as they allow some insights into the underlying mechanisms which are responsible for the profound fat loss effects the researchers observed in the rodent trial. As far as this mechanism is concerned the researchers write in the discussion of their paper:
"The mild exercise routine enhanced fat utilization as energy substrate in both supplemented groups, but not in the placebo group [This went hand in hand with a 21–27%] loss of acylcarnitines in urine [that] has not been found in individuals subjected to low or high intensity exercise without supplement. [...] It may thus be argued that increased demand for energy by exercise in choline/carnitine-preloaded individuals increases rates of fatty acid oxidation, albeit incomplete, resulting in sustained loss of acyl groups in urine." (Hongu. 2003)
I willingly admit that this hardly sounds like an explanation, so let's briefly recap the main points.

Firstly, there is the increase in fat utilization in response to the ingestion of choline and carnitine. Secondly, therese there is the loss of acetylcarnitines, i.e. a complex of carnitine + the short-chain fatty acid acetyl in the urine of the women who participated in the study.
 "Choline promotes carnitine conservation and accretion by tissues that favor incomplete oxidation of fatty acids and disposal of fatty acid carbons in urine as acylcarnitines." (Hongu. 2003)
As the scientists point out, the reason for the latter is an incomplete oxidation of long(er)-chain fatty acids and the net result is a non-negligible loss of energy in the urine. With the addition of caffeine to the equation, the total amount of fat that is available for oxidation during exercise, but more importantly also at rest (not just during exercise) would have increased, the same would apply to the amount of fat that is shuttled into the mitochondria and the amount of fat that will leave the mitochondria only partially oxidized. And what happens if you use more stored fat and use it less efficiently? Correct! The fat depots on your hips, buttocks and abs and if you still have some, the nasty inter-organ fat will be gone faster than without the use of the "CCC" stack. Will it disappear magically overnight and without any dietary and lifestyle changes? Probably not overnight, but maybe over several weeks and months.

Add sugar & phosphate to ameliorate the downregulation of the metabolic rate on a diet

YoYo-Dieting or Constant Gluttony? What Happens During Weight Cycling? And Why Does Every Diet Make You Fatter? I have answered these and related questions in a previous blogpost, already (read more)
Sounds too good to be true? Well in a way it in fact is. After all, this requires a 100% constant food intake and presumes that your body does not adapt its caloric expenditure to achieve a new steady state. That the latter is not very realistic, is probably something many of you have already learned the hard way. after all, those new steady states are actually the underlying reasons of the nasty weight loss plateaus this 2nd part of today's SuppVersity post is dealing with.

"Sugar, orange juice, carrots, ..." does this ring a bell? Yeah, I see you have heard or read about this combination before on the Internet.  No idea yet? Well another hint, then: You usually complement those foods with egg shells, which are a good source of calcium, but not in the form of calcium phosphate, but rather as the simple white powdery calcium carnbonate and thus certainly not what the results of a 1996 study by Nazar et al. would suggest the sugars should be complemented with.

In the said study the results of which were published in the Journal of Physiology and Pharmacology 16 years ago, the researchers from the Polish Academy of Science write that the addition of a phosphate supplement containing non-disclosed amounts of calcium, potassium and sodium phosphate to a 1,000kcal, high viscose fiber diet ameliorated the diet induced reduction in basal metabolic rate in the 30 female overweight study participants (+15 / +19% depending on whether the supplement was taken from week 1-4 or week 5-8 of the 8-week dietary intervention). As Nazar et al. point out, the
"[p]hosphate supplementation ameliorated also a decrease in plasma triiodothyronine level and a decrease in thyroxine to triiodothyronine ratio. [While t]here were no differences between groups in the plasma insulin, catecholamine, growth hormone, cortisol and testosterone levels[,] plasma lipids or blood glucose concentration." (Nazar. 1996)
With the thyroid hormone concentration marking the only statistically significant hormonal difference between the supplementation and placebo phases of in the Nazar studies, the similarities to Dr. Ray Peat's previously alluded highly controversial "sugar for thyroid health protocol" should be obvious.

"Ok, but if it's phosphates instead of calcium, then it must be fat instead of sugar, right? "

Often a picture says more than 1000 words: Normal (left) and repeatedly hypoglycemic rodents (learn more about the obesogenic effects of hypoglycemia)
I bet the above question is now preying on the minds of some of you. "Sugar, really?" It may sound hilarious, but as I've pointed out several times before: An energy deficit, specifically a pronounced one, is a game changer. Things that would usually precipitate weight gain suddenly don't matter, when - at the end of the day - your body has used more energy than it has been able to acquire from the foods you  ate.

Unfortunately your body hates nothing more than having to fight to fulfill his acute energy demands by tapping into its body fat stores and will therefore after a couple of days start to save energy, this is particularly true, when your brain realizes that it's beloved glucose is becoming scarce and there is no abundance of ketone bodies to use instead.

Basically this is exactly the situation that arises on a HCG-like very low calorie (800kcal/day) high protein (95% protein, 4% fat, 1% carbohydrate) such as the one the obese women in a study by Hendler et al. were following at thne Yale Clinical Research Center in the late 1980s (Hendler. 1986). The exact study protocol was a bit complicated (and nonsensical ;-) with half of the patient starting out on what I would prefer to call a 'protein only' diet and not, as the scientists do a "high protein" diet, for 15 days followed by another 15 days on a "sucrose diet" with reversed macronutrient ratios, but identical energy content. The other half dieted for 15 days, only, on the sucrose regimen (I wonder why they did not switch those to the protein regimen afterwards...?!). And one miserable wretch "consumed the high-protein diet for 30 days to serve as a control for the sequential protein-sucrose diet"

HCG like dieting: Don't do this at home!

I guess, I don't have to mention that dietary interventions like these are meant to be used in clinical settings and in very obese individuals. So, don't be bamboozled by the 9kg of body weight the subjects lost within those 30 days and try something similarly stupid at home. Our interest in this study is merely related to the effects on the resting metabolic, which were (I will list the main effects and quote excerpts from the results):
  • Figure 3: Effect of the sequential protein-sucrose diet on resting metabolic rate (RMR), serum triiodothyronine (T3) and plasma norepinephrine concentra- tions (Hendler. 1986)
    significant reductions in resting metabolic rate during the protein phase: "After 15 days of the hypocaloric protein diet, resting metabolic rate decreased by 354 kcal/day, or 21 percent of control values (p < 0.01)"
  • restorative effects of the sucrose diet in the subsequent 15 days: "Sucrose substitution significantly increased the resting metabolic rate (+228 kcal/day, p < 0.05) to values approaching those in the control period (p = NS)."
  • metabolic shut-down in the poor wretch who followed the protein only diet for 30 days: "In contrast, the single patient given the protein diet continuously for 30 days showed a progressive decline in resting metabolic rate (2,165, 1,822, and 1,628 kilocalories per day at baseline and after 15 and 30 days of the protein diet, respectively)." 
  • Plummeting levels of the active thyroid hormone T3 that were only partly restored in the sucrose phase: "Changes in serum triiodothyronine levels followed the pattern of diet-induced changes in resting metabolic rate. The serum triiodothyronine level fell by 41 percent (p < 0.02) after the protein diet and then rose (by 28 percent, p < 0.02) after sucrose substitution, reaching values intermediate between control and protein diet levels. 
  • Significant correlations between the drop in T3 levels and the lowered metabolic rate: "There was a significant correlation between the changes in the serum triiodothyronine level and resting metabolic rate during the sequential diets (r = 0.701, p < 0.01).
  • Only minimal signs of a reduced sympathetic tone in the protein phase, none in the succrose phase: "Supine norepinephrine concentrations were slightly, but not significantly, reduced by the protein diet (10 percent) and failed to change significantly when sucrose was substituted. 
  • No correlation between epinephrine and the resting metabolic rate: "There was no correlation between changes in the supine norepinephrine concentration and resting metabolic rate."
Interestingly, no significant changes in any of the measured parameters, i.e. serum triiodothyronine (T3) levels, epinephrine and, most importantly, the reductions in metabolic rate were observed in the patients who followed the succrose diet.

 Does it make sense to eat carbs on a lean bulk as well, or will they just make you fat *scary sound*? Learn more in a previous SuppVersity post.
So what's the take home message, here? Don't worry, as I've already pointed out, I am neither suggesting that you should follow a pure sugar nor a 800kcal diet. And you can be sure that the negative effects on the resting metabolic rate are "diet dose depend" (meaning the harder and imbalanced you diet, the more pronounced they will be). What I am suggesting is that there is reason I keep repeating my mantra "you cannot live on protein alone", both here, as well as on the SuppVersity Science Round-Up. So if you insist on going on a "low carb diet" you better do it right and turn to a  high fat diet (<15% protein), use regular really high carb (including sugar!) refeeds or periods of normal high(-ish) carb intake to keep your metabolism chugging along nicely.
A final note on a possible CCC protocol: I actually did not want to write that down, but I know you will be asking anyways. Please keep in mind though, that I cannot tell you the optimal dose and that I have more than just second thoughts about taking high amounts of choline (see potential side effects next to the respective bullet point below).
  • Max. (!) 3g choline: Take the choline (bitartrate or citrate, no funky GPC or similar junk) with meals split across the day, but refrain from taking the human equivalents (HED) from the rodent study, I suppose 3g could already make you smell like a fish. Watch out for potential side effects, such as cramps, nausea, vomiting, dizziness, high blood pressure, or acne-like skin rash. Stop the supplement immediately, if you experience any of those. Also make sure to get adequate amounts of potassium and magnesium.
  • 3-5g of carnitine: Stick to the l-tartrate or regular form of carnitine. Take the carnitine in 3 doses best on empty (learn more about in the Amino Acids for Super Humans Series). 
  • 200mg sevings of caffeine: Use the caffeine whenever you are fasted for at least 90min or before you are working out. Don't take more than 400mg, max. 600mg per day and - needless to say - don't take it before bed.
Again keep an eye on side effects and don't expect any miracles! This is a supplement to help you lose fat, not to make you lose fat.
Once you've got these fundamentals right you may want to consider adding in the CCC stack and a phosphate supplement to promote - not to induce - fat loss.

  • Hendler RG, Walesky M, Sherwin RS. Sucrose substitution in prevention and reversal of the fall in metabolic rate accompanying hypocaloric diets. Am J Med. 1986 Aug;81(2):280-4.
  • Hongu N, Sachan DS. Caffeine, carnitine and choline supplementation of rats decreases body fat and serum leptin concentration as does exercise. J Nutr. 2000 Feb;130(2):152-7.
  • Hongu N, Sachan DS. Carnitine and choline supplementation with exercise alter carnitine profiles, biochemical markers of fat metabolism and serum leptin concentration in healthy women. J Nutr. 2003 Jan;133(1):84-9.
  • Nazar K, Kaciuba-Uściłko H, Szczepanik J, Zemba AW, Kruk B, Chwalbińska-Moneta J, Titow-Stupnicka E, Bicz B, Krotkiewski M. Phosphate supplementation prevents a decrease of triiodothyronine and increases resting metabolic rate during low energy diet. J Physiol Pharmacol. 1996 Jun;47(2):373-83.
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