Wednesday, May 9, 2012

High Dose Caffeine + Non-Alcoholic Fatty Liver Disease = 355% Increased Very Low Density Lipoprotein (VLDL)

Image 1: Already in "pill form" - Coffee beans
Caffeine, the world's #1 drug certainly is a remarkable substance. It does not only have myriads of well-established physiological effects, already, but it seems that - if you wanted to - you could identify another one everyday. It is thus not really surprising that a recently published study by Abd El-Ghany, M.A., Rasha, M. Nagib and Hagar, M. El-Saiyed from the Mansoura University in Egypt casts yet another, in this case, however, pretty scary light on the lifeblood of the average Starbucks junkie (El-Ghany. 2012).

Caffeine prevents weight gain - whohooo! Or not?

The scientists set out to investigate the differential effects the oral administration of 10mg/day of pure caffeine, or dose-equivalents from coffee, (black) tea, cacao and Nescafe (note: this is my understanding of the somewhat sloppy English translation of the methods) would have on the lipid levels of rats who had been pretreated with a lard-based high fat diet and CCl4 for three months. This treatment had elucidated the expected inflammatory response and fatty acid deposition in the livers of the animals that were then randomly assigned to either one of the 5 treatment or a non-treated control group.
Figure 1: Weight gain (relative to initial weight) and food intake in non-treated, caffeine, cacao, Nescafe, coffee, or black tea treated rodent model of NAFLD (data adapted from El-Ghany. 2012)
And when you peak at the study outcome in figure 1 I would bet that your first reaction is: "Hey, cool! I must ramp up my caffeine intake even more, then!" We are in fact so conditioned to believe that weight loss, or the absence of weight gain is a "good thing" that I made the same stupid mistake, when I first looked at the (in the study) tabular data of the El-Ghany study. Then, I began to wonder: "How come that coffee and cacoa, of which I have repeatedly read that they help with weight loss, did increase the weight gain to levels that were higher than those in the non-treated control group." Finally, it dawned on me: What we are dealing with, here, is not weight loss or ameliorated weight gain, what we are seeing in all the groups is more of a special form of "failure to thrive"! After all, the non-CCL4 treated 'real' control group (data not shown in figure 1) did gain 45% of their initial body weight and thus still 15% more than the coffee group, of which I was mislead to believe that they "performed" worst.

High dose caffeine is for NAFLD sufferers not!

Looking at the rest of the data it became increasingly clear, the whopping dose of 10mg of caffeine per rodent per day, a dose, by the way, which happens to translates into a human equivalent dose of 10mg/kg (i.e. 800mg for an 80kg adult), did a pretty decent job in liberating fatty acids from the adipose tissue. So "decent", in fact, that the already compromised weight gain in those sick creatures was further attenuated.
Figure 2. Lipid levels in the treatment groups expressed relative to non-treated NAFLD rodents (left); selected liver slices (right; based on El-Ghany. 2012)
But it gets even worse, the sudden influx of fatty acids from the adipose tissue was so overwhelming that the already damaged livers of the NAFLD rodents started to spill out copious amounts of very low density lipoprotein (VLDL) - those nasty little cholesterol molecules of which researchers believe that they are the cause of cardiovascular disease. And despite the fact that we do not have any tissue images of the heart, the congested vein in the liver slice from one of the caffeine guzzling rodents appears to confirm the causal relationship of VLDL and clogging of the blood vessels; an effect, by the way, which could neither be countered by the -71% reduction in triglyceride levels, nor the -44% reduction in total lipids (compared to non-treated NAFLD control). 
Figure 3: Total cholesterol (CHO) and LDLc to HDL-c ratios in the non-treated, as well as the treated groups expressed relative to non-NAFLD control (data calculated based on El-Ghany. 2012)
In a 1985 letter to the editor of the Journal of the American Medical Association (Jama) William and Simpson explain the sudden occurrence of enormous amounts of VDLD in response to the lipolytic (=fat liberating) effects of caffeine as follows:
Upon liberation from the adipocyte, fatty acids are transported to the liver, where they are reesterified and the resultant triglycerides packaged for release in very-low-density lipoprotein (VLDL), which also contains apolipoprotein B.
If we assume that this hypothesis is correct, coffee, cacao and even Nescafe must obviously contain substances which help the liver to cope with the additional influx of fatty acids, as the animals in the respective groups do not only have significantly lower VLDL levels than the poor critters in the caffeine group, but also exhibit the most beneficial total cholesterol-to-HDL and LDL-to-HDL ratios (cf. figure 3) of all groups.

Say no to stims, energy drinks and coke and chose natural caffeine sources

In view of the ameliorative effects all the caffeine containing preparations had on the pathological features of NAFLD (cf. figure 2, right), and based on the results from previous studies and the assumption that the VLDL increase in the tea group was similarly well-handled in the rest of the body as it was in the liver, which did not present any of the congested veins that were so characteristic of the livers of the animals in the caffeine only group, the take home message of this study is one every SuppVersity student should be familiar with, by now: Nature knows best!
Image 2: I don't have to tell you that the study at hand suggests that those sugary caffeine bombs people call "energy drink" could give many of their livers their quietus.
Note: If you live in Dallas County, it does take no more than three attempts to identify a neighbor, friend, someone from your family or simply a pedestrian being in the early stages of NAFLD. And given the fact that the 33.6% NAFD rate in Dallas County was measure in 2005 already (Szczepaniak. 2005), it is almost certain that your neighbors' liver, which may still have been comparably healthy in 2005 has caught meanwhile. The results of this study could thus have greater implications on public health than you may initially have thought and it clearly suggest that the use of high dose "fat burners" and / or pre-workout supplements, as well the regular consumption of caffeine and sugar laden "energy drinks" or even coke is absolutely contra-indicated; and that not just in the obese, but also in the insulin resistant normal weight, whose liver is often similarly clogged with fat as the one of his 200lbs heavier comrade in crime.
If the caffeine is ingested in the absence of its natural adjuvants bad things happen. If they remain where they belong, however, the same whopping dose of caffeine that makes things worse could actually turn into a decent "liver fat burner".

While Coffee, tea and cacao drinkers can thus breathe a sigh of relieve, the average stim junkie who is already squirreling caffeine laden, geranium (DMAA) intoxicated pre-workout supplements and fat burners for the days after the DMAA ban, should better watch his liver health. Otherwise it may well be that he or she will end as a "case study" in the library of the FDA - filed under "death by fulminant liver failure induced by geranium + caffeine containing pre-workout supplement" - btw. isn't it strange that the FEDs don't have such a case study for one of the commercially available energy drinks, or even plain Coke, already?