High Dose Caffeine Restores Insulin Sensitivity and Limits Total as Well as Visceral Fat Gain Due to High Sugar Diets

High Dose Caffeine Restores Insulin Sensitivity and Limits Total as Well as Visceral Fat Gain Due to High Sugar Diets

caffeine coffee fat gain glucose management health high sugar insulin sensitivity lose fat obesity sugar type II diabetes visceral fat

Yes, the study at hand is on caffeine, but the results are relevant for coffee, too.

A decade ago, the medical community though coffee would dehydrate you, would make you insulin resistant and would increase your risk of heart disease. Recent studies show that coffee does not negatively affect your hydration status (Killer. 2014), that higher coffee consumption is associated with reduced diabetes risk and increasing your coffee consumption can reduce your risk of T2DM (Akash. 2014) and that a "daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects" on coronary heart disease, congestive heart failure, arrhythmias, and stroke (O'Keefe. 2013).

Against that background it may not be as surprising as it would have been 10 years ago that Joana C. Coelho, et al. (2016) found caffeine to be able to restores insulin sensitivity and glucose tolerance in high-sucrose diet rats. And yet, I personally believe that it is still worth pointing out the results of this study as the high sucrose diet the mice were fed is the same "high sugar diet" about which you will read all over the news that it is to blame for the obesity and diabetes epidemic.

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Against that background, it is particularly interesting to take a closer look at the data from Coelho's study, because it is the first to actually provide a valid explanation for the observed improvements in glucose sensitivity in response to the ingestion of caffeine.

Figure 1: 16-wk food intake, weight gain, fat gain and visceral fat gain according to caffeine intake (Coelho. 2016).

Now, the bad news is that significant effects were only observed for the highest dose of caffeine, ie..e 1g/L drinking water. That appears to be ridiculously high, but is in fact only "very high". If you do take into consideration that a wistar rat consumes only 100 ml/kg body weight per day, that's a dosage equivalent of 100 mg/kg for a rodent and thus ~16 mg/kg for a human being or ~6-7 cups of coffee (over a 24h period).

University of Memphis: Caffeine can help control the increase in blood lipids and oxidation after inhaling (10 minutes) a high calorie + high fat milk shake, controlled trial involving twelve healthy men shows (Crone. 2016).

Yes, the dosage is high, but actually less may have more benefits, and...  the most relevant benefits (reduced fat gain) were seen at a dosage that would be equivalent to only 4-5 cups of coffee, which happens to be roughly what epidemiological studies show to be in the zone of maximal benefits. Don't mistake this as a recommendation to guzzle liters of coffee, though... and that even if another recent study shows that 400mg of caffeine will lower the fatty acid onslaught and oxidation 12 men experience after consuming a large high fat milk-shake (Crone. 2016)... and speaking of coffee: you may also want to make sure to get a dark roast, because the latter has just been found to improve glucose metabolism and redox balance even if it is low in caffeine (Di Girolamo. 2016). 

While I am not sure how healthy the chronic consumption of these amounts of caffeine actually is. I am aware of several people who get their 6-7 cups of regular coffee per day and are in perfect health. With that being said, the latter may be at least partly due to the the highly beneficial effects of caffeine on the expression of glucose transporter 4 (GLUT4) and insulin receptor expression and phosphorylation (not shown in Figure 2) in the visceral fat depots of coffee connaisseurs.

Figure 2: Effects of different doses of caffeine on GLUT4 and insulin receptor expression in rats (Coelho. 2016).

The above elevations were accompanied by profound increases in protein kinase B (Akt) expression and activity, as well - an observation the scientists regard as being evidence of the fact that "[c]hronic caffeine administration improved whole-body glucose homeostasis and insulin signaling pathways in adipose tissue" (Coelho. 2016).

This conclusion cannot be questioned. What can be questioned, though, is the scientists assumption that this would occur only with high doses of caffeine and in response to increases in GLUT4 and insulin receptor expression in the visceral fat. Why's that? Well take a look at the figure in the bottom line: it shows that significant improvements in glycemia were improved at all dosages. The latter wouldn't have been possible if the lower dosages wouldn't have had an effect on glucose uptake, as well. Whether that's an effect in muscle cells (which would be great), needs further investigation. The previously discussed effects of caffeine on muscle glycogen storage (learn more), on the other hand, would suggest just that: an effect on skeletal muscle, and or a reduction in gluconeogenesis which could, among other things, be triggered by coffee's / caffeine's ability to inhibit the reactivation of glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1" (Atanasov. 2006).

As you can see sign. improvements in glycemia occured even with the lowest amount of caffeine in the drinking water. And that in spite of the fact that the GLUT4 and insulin receptor levels in the visceral fat did not increase significantly... well, maybe those in the rodents' muscle did?

Bottom line: I am not suggesting that the rodent study at hand would provide enough evidence to suggest that everyone should drink at least 4 cups of high caffeine coffee per day. What I do suggest, however, is that the study at hand provides more evidence on potential mechanisms that explain why coffee drinkers are plagued less often by metabolic disease.

With that being said, I would like to remind you that the abuse of caffeine to combat a lack of sleep and/or overtraining may make you dig a deep black hole out of which you will be able to crawl only within weeks of abstinence... and I am talking about abstinence from caffeine and exercise, assuming that it was the combination of both that got your into trouble | Comment on Facebook!

References:

• Akash, Muhammad Sajid Hamid, Kanwal Rehman, and Shuqing Chen. "Effects of coffee on type 2 diabetes mellitus." Nutrition 30.7 (2014): 755-763.
• Atanasov, Atanas G., et al. "Coffee inhibits the reactivation of glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1: A glucocorticoid connection in the anti-diabetic action of coffee?." FEBS letters 580.17 (2006): 4081-4085.
• Coelho, Joana C., et al. "Caffeine Restores Insulin Sensitivity and Glucose tolerance in High-sucrose Diet Rats: Effects on Adipose Tissue."
• Crone, et al. "Impact of Meal Ingestion Rate and Caffeine Coingestion on Postprandial Lipemia and Oxidative Stress Following High-Fat Meal Consumption." Journal of Caffeine Research (2016): Ahead of print. DOI: 10.1089/jcr.2016.0004.
• Di Girolamo, Filippo Giorgio, et al. "Roasting intensity of naturally low-caffeine Laurina coffee modulates glucose metabolism and redox balance in humans." Nutrition (2016).
• Killer, Sophie C., Andrew K. Blannin, and Asker E. Jeukendrup. "No evidence of dehydration with moderate daily coffee intake: a counterbalanced cross-over study in a free-living population." PloS one 9.1 (2014): e84154.
• O'Keefe, James H., et al. "Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality." Journal of the American College of Cardiology 62.12 (2013): 1043-1051.

Interaction of Fat Cell Size, Protein Intake & Co. W/ Fat Gain + Insulin Res. in Overfed Men + Women in Metabolic Ward

Interaction of Fat Cell Size, Protein Intake & Co. W/ Fat Gain + Insulin Res. in Overfed Men + Women in Metabolic Ward

adipocyte size fat cell fat cell sizes gain fat gylcemia health high protein homa-ir insulin insulin resistance lose fat overfeeding subcutaneous fat visceral fat visceral obesity

That's rather the low protein variety of overfeeding... but wait, was the high protein diet even "high" in protein? Well high enough to affect liver fat, for sure.

You will probably remember José Antonio's high protein overfeeding study series (learn more) from the articles here and on the SuppVersity Facebook page. The results were quite impressive, but the number of controlled covariates were small and the dietary control was limited to food logs.

In a more recent study, George A. Bray and colleagues from the Pennington Biomedical Research Center of the Louisiana State University System, the George Mason University, and the FL Hospital & Sanford-Burnham Prebys Discovery Research Institute (Bray. 2016) determined the effect of overfeeding diets with 5%, 15% or 25% energy from protein on glycemia + body fat distribution in healthy men and women with add. covariates and in a metabolic ward.

Yes, the high protein intake clogged the liver during overfeeding

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In total, 15 men and 5 women were overfed by 40% (extra calories above maintenance) for 56 days with diets containing

• 5% (LP) of the total energy as protein, 
• 15% (NP) of the total energy as protein, or 
• 25% (HP) of the total energy as protein

Insulin sensitivity was measured using a two-step insulin clamp at baseline and at 8 weeks. Body composition and fat distribution were measured by DXA and multi-slice CT scan ... so far not so different, but the subjects were contained in a metabolic ward, cheating on the diet was thus as impossible, as taking supplements or working out like maniacs.

Figure 1: Diagram that illustrates the 8-weekstudy design; N = 10 male, 5 female subjects (Bray. 2016).

In conjunction with the scientists' analysis of the subjects abdominal subcutaneous fat cell size, which was determined on osmium fixed fat cells, these are two strengths of a study, of which it is yet quite obvious that it also had its disadvantages:

• 

  Review the effects of different macronutrients in overfeeding studies | more

  the protein content of the diet is simply hilarious - that's not just because eating 5% protein, only is nothing but idiotic, but also because 25% of protein is far away from what can be considered "high protein" these days;
• the lack of exercise limits the significance of the results - at least for the majority of SuppVersity readers overeating in phases in which you don't exercise is probably nothing they would even remotely consider.

The scientists observations that neither the subjects' insulin sensitivity and free fatty acids during low and high levels of insulin infusion did not differ after 8 weeks of overfeeding.

Figure 2: Effect of 8 weeks of overfeeding on abdominal fat distribution, ectopic lipid; rel. changes (Bray. 2016).

What did differ, however, were the changes in body fat distribution according to DXA and how the latter depended on the protein content on fat cell size before the overfeeding period. More specifically, ...

• the fat free mass (FFM) and intrahepatic lipid increased more on the high protein, whereas 
• % BF and fasting free fatty acids (FFA) increased more on the low protein diet, while

In addition, the scientists observed that a high initial fat cell size predicted increased visceral fat gains and the FFA suppression during the high-dose insulin clamp.

Figure 3: Relation of Baseline Fat Cell Size to Change in Visceral Adipose Tissue Mass with Eight Weeks of
Overfeeding in heathy volunteers (VAT 0.040 +/- 0.70(FCS); P < .0063 | Bray. 2016)

The subjects' insulin levels at baseline, on the other hand, predicted the increase in subcutaneous but not visceral fat accumulation (see Figure 3) - most intriguingly with low fasting insulin
at baseline correlated predicting higher changes in % fat (for insulin the scientists observed a correlation with r = –0.43; P < .034), but not with other variables. It is thus not surprising that the most insulin sensitive subjects also gained the most subcutaneous fat... or, as the scientists put it: "HOMA IR predicted the increase in DSAT (r = 0.50; P <.016), but not other variables" (Bray. 2016).

Those are important insights of which the authors rightly point out that they clearly indicate that "an induction of insulin resistance with overfeeding is related to fat cell size and requires more than an expansion of adipose tissue stores" (Bray. 2016).

A surprising, but not debatable result of the study at hand is that the high protein diet increased liver fat (HUs;  measured with DXA, too).  The low protein diet, on the other hand, helped to decrease the subjects' liver fat significantly - remember: we are talking about a diet with 40% extra energy on top of the regular diet (Bray. 2016).

Bottom line: Yes, you've read all that in individual articles (albeit often about rodent studies) on SuppVersity before: (1) the more protein, the greater the lean mass gains; (2) the less protein, the greater the ratio of fat to lean mass gains; (3) the fuller your fat cells, the more likely you will gain metabolically unhealthy visceral fat; and (4) the more insulin sensitive you still are, the more metabolically healthier subcutaneous fat you will gain.

What is news, or at least has not been observed in Antonio's study in active individuals (also because they didn't look) is the surprisingly ill effect of high amounts of protein on liver fat (see Figure, right): while the low protein diet reduced the subjects' liver fat sign, the high protein diet triggered a small, but undesirable accumulation of liver fat during overfeeding in normal-weight subjects - not good, but not yet critical and hopefully something you'd not see w/ concomitant exercise or smaller calorie excess | Comment!

References:

• Bray, George A., et al. "Effect of three levels of dietary protein on metabolic phenotype of healthy individuals with 8 weeks of overfeeding." The Journal of Clinical Endocrinology & Metabolism (2016): jc-2016.

Fat-Blocker Effect of Tea Catechins Confirmed (?) in Man - Sign. Abdominal Fat Loss (5-8%) in 12 Weeks W/Out Diet

Fat-Blocker Effect of Tea Catechins Confirmed (?) in Man - Sign. Abdominal Fat Loss (5-8%) in 12 Weeks W/Out Diet

abdominal fat catechins ecg EGCG green tea GTE intra-abdominal fat lose fat lose weight obesity subcutaneous fat tea visceral fat visceral obesity

Tea catechins (which can also be found in black and jasmin tea | see Figure 3) can help you keep particularly unhealthy abdominal fat (Després. 2012) at bay.

It is one thing to have in-vitro and rodent data that green tea can inhibit the digestion of dietary fat (reported previously in the SuppVersity Facebook News); it is another thing, however, to have a human study like the one Makoto Kobayashi and colleagues are about to publish in the peer-reviewed scientific journal Food & Function that shows that the "[i]ngestion of a green tea beverage enriched with catechins with a galloyl moiety (THEA-FLAN 90S) during a high-fat meal reduces body fat in moderately obese adults" (Kobayashi. 2015).

Ok, the abdominal fat loss does not, as the previous quote from the conclusion appears to suggest, occur instantly right after you've consumed your first tea w/ a single meal.

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Rather than that, 124 subjects (two of the initially 126 subjects 2 dropped out for personal reasons unrelated to the trial), 53 men, 71 women, who consumed similar, albeit non-standardized diets (see Figure 1 | note: physical activity was also identical) and began the study with body fat levels of ca. 31-35% had to consume the previously mentioned tea beverage that contained tea catechins (250 mL with 215.3 mg green tea catechins containing 211.0 mg green tea catechins with a galloyl moiety) twice or three times daily during mealtimes for 12 weeks, before the significant reduction in body fat became visible.

Figure 1: Macronutrient composition (in g an % of energy) of the non-energy reduced diets the subjects consumed; the values in the left pie chart represent a group average of all three intervention groups. Since the data is based on food records with photographs, it is probably more reliable than in your average diet study (Kobayashi. 2015).

Now, in view of the fact that this is not the first study to demonstrate weight loss effects in overweight subjects consuming green tea or, as in most other studies, green tea extracts, the word "during" and thus the fact that the green tea beverage was consumed with at least two of the three meals per day should be highlighted as a specific feature of the study at hand that is highly relevant to its interpretation.

Figure 2: Detailed analysis of the rel. change in fat area in the abdominal depot of the subjects (Kobayashi. 2015)

It is after all the requirement that the green tea beverage had to be consumed with a (preferable high fat) meal that allows the authors to conclude that the significant fat loss Kobayashi et al. measured by the means of computer tomography predominantly in the abdominal area are the result of an inhibition or slowing of the intestinal fat absorption and thus warrant the conclusion that "the ingestion of green tea beverages enriched with CGM together with high-fat meals may be an effective strategy for reducing body fat in moderately obese adults" (Kobayashi. 2015) - an observation of which I would like to add that the underlying mechanism is not 100% certain.

What about weight and, even more importantly, muscle loss? No, losing lean mass was not an issue in, because weight loss (-0.6 and -0.8% in the low and high dose group, respectively | measured by bio-electrical impedance vs. computer tomography as it was the case for the abdominal fat area) was actually not an issue, either. If you want to measure your success on the scale, green tea is thus not going to be the "diet tool of choice" (unless you use it alongside an energy-reduced diet)... however, if you take into account that the placebo group actually did what the average Westerner does, these days, i.e. gain weight and body fat over the 12-week study period, you may argue that you can still see the results on the scale which could finally stand still after years of displaying subtle, but eventually relevant increases in body weight.

The authors base their conclusion that it is "unlikely that absorbed green tea CGM leads to increased energy expenditure, followed by reduced abdominal body fat area" (Kobayashi. 2015) on two reasonable, but experimentally (in this study) not confirmed assumptions which are that little to no catechins actually made it into the bloodstream, because ...

1. the low caffeine content of the beverage limits the bioavailability of EGCG & co (caffeine enhances its bioavailability | Nakagawa. 2009) and
2. the ingestion of the beverage with a meal has been shown to significantly reduce the bioavailability of green tea catechins in comparison to the fasted state (Chow. 2005).

The assumption that its just a blockade of the digestion of fat becomes even more questionable, if you (re-)read my 2014 article on the carb blocking effects of tea... Well, eventually, though, you may argue that it does not matter if the reduction in abdominal fat was due to thermogenic effects, thermogenic and fat-blocking effects or, as the scientists believe, mediated exclusively an "inhibit[ion] or slowing [of the subjects'] intestinal fat absorption" (Kobayashi. 2015). And let's be honest, I guess you're right. What matters is that there were significant reduction ins abdominal fat (visceral, subcutaneous and total abdominal fat area). Reduction of which the data in Figure 2 tells you that ...

1. 

   Table 1: Catechin composition of the test beverages.

   the fat loss in the abdominal area was dose dependent - even if the differences between the low and high dose group did not reach statistical significance (for the exact catechin composition see Table 1 on the right) - and that 
2. roughly 50% of the benefits were lost within only 5 weeks when the subjects stopped consuming the green tea beverage, even though their diet didn't change at all (in fact, they consumed minimally less energy in the withdrawal phase from week 12-17).

Now, (b) is obviously good news for green tea lovers, but bad news for those who cannot imagine consuming green tea containing beverages "for the rest of their lives".

Green tea forever, it is then!? Well, as usual we have to consider what limits the generalizability of the results. Firstly, we are dealing with a group of people who have more than a few pounds of extra-weight on their hips. An abdominal fat loss of 8% in 12 weeks is thus not impossible, but not exactly likely to be seen in someone who starts at a body fat percentage of 15% or less (which is half what the subjects in the study at hand began with).

Figure 3: Catechin content (mg/10ml) of black, green and jasmine tea prepared from commercial tea w/ different infusion times (Bronner. 1998).

The second thing we have to keep in mind is the beverage itself. As you've previously read, it has been enhanced with catechins with a galloyl moiety (CGMs | EGCG, ECG, GCG, CG). Does this mean that you cannot achieve similar results if you simply drink green tea? Luckily, data from Bronner, et al. (1998) suggests otherwise. As you can see in Figure 3, it would take only 100 ml of commercially available freshly brewed (infusion time 3 min) green tea and even less black tea to achieve similar concentrations of EGCG and the other catechins with a galloyl moiety in your tea. Accordingly, the second obstacle to the gene- relizability of the study is actually irrelevant.

Third- and lastly, there's yet still the fast reversal of the effects which suggests that it is necessary to become a habitual tea drinker to see long-term / lasting benefits of green tea (or as the data in Figure 3 suggests even catechin containing tea in general) on your body weight and, more importantly, body fat you're carrying around | Comment on Facebook!

References:

• Bronner, W. E., and G. R. Beecher. "Method for determining the content of catechins in tea infusions by high-performance liquid chromatography." Journal of Chromatography A 805.1 (1998): 137-142.
• Chow, HH Sherry, et al. "Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals." Clinical Cancer Research 11.12 (2005): 4627-4633.
• Després, Jean-Pierre. "Body fat distribution and risk of cardiovascular disease an update." Circulation 126.10 (2012): 1301-1313.
• Kobayashi, Makoto, et al. "Green tea beverages enriched with catechins with a galloyl moiety reduce body fat in moderately obese adults: a randomized double-blind placebo-controlled trial." Food & Function (2016).
• Nakagawa, Kiyotaka, et al. "Effects of co-administration of tea epigallocatechin-3-gallate (EGCG) and caffeine on absorption and metabolism of EGCG in humans." Bioscience, biotechnology, and biochemistry 73.9 (2009): 2014-2017.