10 Days of 'Paleo Life in the Wilderness' Will Strip up to 18 cm off Your Waist and Boost Your Insulin Sensitivity by 53%

10 Days of 'Paleo Life in the Wilderness' Will Strip up to 18 cm off Your Waist and Boost Your Insulin Sensitivity by 53%

diet health insulin insulin sensitivity lifestyle lose fat metabolic syndrome paleo paleo lifestyle physical activity

Even though it may have been funny, this is not exactly how the scientists simulated the "paleo lifestyle" in the study at hand. Eventually, however, it came down to eating healthier, being active and even being stressed (within the limits of natural "paleo stress", though).

No, this science website is not going to turn into a paleo blog, ... don't worry. It's mere coincidence that this is the 2nd "paleo" study in 2 weeks that is interesting enough to get its own SuppVersity article devoted to it (last one).

Moreover, said study, which was published in the peer-reviewed scientific journal BioMed Research International, recently (Pruimboom. 2016), doesn't even have the world "paleo" in title of full-text and could still be called "the true paleo" study. It does, after all, revolve around a 10-day mimic of a "hunter-gatherer lifestyle" and its favorable effects on anthropometrics and clinical chemical indices such as the reductions in insulin, triglycerides, HDL, elevated liver health markers and other indices that are usually far from being optimal in the average student, scientist, physician, and other health professionals who participated in the study at hand.

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As the researchers point all, all subjects (n=10, n=32 and n=11) "were interested to experience the impact of ancient lifestyle on their own health and well-being and therefore jointly decided to engage in this study" (Pruimboom). In that, the term "this study" refers to three separate 10-day trips through the Spanish Pyrenees during the summers of 2011 (𝑛 = 10), 2012 (𝑛 = 32), and 2013 (𝑛 = 11), on which ...

"[t]he participants lived outdoors and walked from one watersource to another. Food was provided by the organization and with help of forest-guards from official institutes of the Catalan county. Food intake was planned before the trip, based on the average daily food intake by the traditionally living Hadzabe people in Tanzania. The use of mobile phones or other electronic devices was not allowed" (Pruimboom. 2016)

It is obviously debatable, if "mayonnaise" is a paleo food (not sure if they made it themselves) and how "paleo" the rest of the subjects' diet which may have been designed to mimic the macros, but probably not the foods of the Hadzabe (see Figure 1, tabular overview on the left) actually was.

Figure 1: Exemplary food intake (left) and changes in anthroprometrics (right); stat. sign. w/ p < 0.001 was observed for the median changes, not the minimal and maximal changes, obviously (Pruimboom. 2016).

What is undebatable, though, is the statistical significance and health relevance of the reductions in weight and body fat you can deduce from the sign. reduction in the median subjects' waist circumference.

Mind the statistics: There's a reason why I plotted more than one value in Figure 1. While I cannot tell you the reason why, I can tell you that at least one subject did not see the expected improvements in waist circumference. Possibly, he or she ate too much mayonnaise ;-), ... Why's that relevant? Well, it obviously goes to show you that calories still count. While the median subjects (with the low number of participants the scientists didn't calculate averages) obviously was in a caloric deficit, this one person probably just wasn't caught feasting secretly on the supply.

It should be noted, though, that these changes were certainly not attributable solely to the diet. Rather than that it should be obvious that the significant reduction in body and most certainly belly fat was the consequence of (a) what and how much the subjects ate while (b) experiencing what the Dutch scientists call "ancient stress factors" they were facing during a 10-day trip that revolved around the following four principles:

• Walking and limited manual work- providing the exercise / general physical activity stimulus modern humans lack: There were daily walking trips from waterhole to waterhole, with an average walking distance of about 14 km/day, including altitude differences up to approximately 1,000 m. The participants carried their own backpacks with an average weight of 8 kg. The trip took place in the part of the Pre-Pyrenees with a maximum altitude of 1,900 meters above sea level. In addition, some manual work was done to clean mountain trails as agreed upon with the Catalan Government.
• Intermittent fasting - leaving room to actually experience hunger and all its beneficial hormonal correlates (e.g. AMPK increase => mitochondrial housekeeping, etc.): Participants consumed two meals daily. The first meal was provided by the organization halfway and the second meal prepared on arrival at the camping site. Animals, including ducks, chickens, turkeys, rabbits, and fish, were delivered alive and killed by the participants. Fish were caught with nets in the Noguera river. All foods were prepared on the spot by the participants.
• 100% exposure to the elements - resynchronizing the internal clock: The participants slept outside in sleeping bags on small inflatable mattresses. Outside temperatures varied from 22 to 42∘C during daylight, whereas night temperatures varied from 12 to 21∘C. One group experienced a day of snow in the middle of July, which prompted the organization to provide hotel accommodations for a single night.
• Cyclic water intake - experiencing thirst to benefit from the anti-inflammatory release of oxytocin (Krause. 2011): Bulk (intermittent) drinking behavior was recommended by drinking as much as possible (up to satiety) after reaching a waterhole. The waterholes contained nonchloritized drinking water (Note: I would not suggest using "dehydration" as a means to improve your health; while it may have done this in the study at hand, it's simply stupid - and that's in the literal sense, as you've read in my article "Hydrated or Dumb").

Only in conjunction, with these "stress factors" did the diet do its body fat reducing and, as the data in Figure 2 shows, glucose and blood lipid reducing effects:

Figure 2: Changes in glucose and lipid metabolism over (I repeat) only 10 days; worth mentioning: all but the effect on HDL were statistically highly sign. with p < 0.001 (Pruimboom. 2016).

Effects of which the scientists say that they were the result of acute stress, which promotes release of stress hormones, including adrenaline, noradrenaline, and cortisol, all of which are bad in excess, but will "give rise to recovery from the reigning state of chronic low-grade inflammation and the return to homeostasis" (Pruimboom. 2016), when the stressors are hit the sweet spot of hormesis as it occurred in response to / corollary with the elevation in AST, ALT and hs-CRP of which I've explained previously that all of them can be natural reactions to (especially unaccustomed) physical activity (learn more about ALT, AST and exercise induced inflammation that may be misunderstood as a health problem).

In the study at hand, said "recovery from the reigning state of chronic low-grade inflammation" was characterized by "profound metabolic and immunologic adaptations", of which the scientists highlight that they relate to three classic features of the metabolic syndrome, i.e. body mass, glucose homeostasis, and circulating lipids. The fourth, i.e. blood pressure was - unfortunately - not recorded.

Ad-Libitum Paleo Diet W/ a Handful of Simple Rules Cuts 5-7 kg of Body Fat in 12 Weeks - Plus: Paleo Research Overview | more.

Bottom line: With the metabolic syndrome, also named the insulin resistance syndrome, being "a well-established risk factor for various diseases of affluence, including type 2 diabetes, cardiovascular disease, essential hypertension, polycystic ovary syndrome, nonalcoholic fattyliver disease, certain types of cancer (colon, breast, and pancreas), sleep apnea, and pregnancy complications, such as preeclampsia and gestational diabetes", the scientists are right to highlight in their conclusion that the subjects didn't just feel better subjectively (according to questionnaire), but returned from the "wilderness" in an objectively healthier state.

A state of which the scientists say that it has been promoted by the previously discussed consequences of the four pillars (see list) and related effects, such as the reduction of the postprandial inflammatory response (Holmer-Jensen. 2011; Klop. 2011; Peairs. 2011) and increased protection against pathogens (Fielding. 2000; MacEneaney. 2009) that occurs, when you are physically active before a meal. Even the presence of "cutaneous- and other body surface-directed danger signals" could, as Pruimboom et al. point out have been "hormetic triggers" | Comment!

References:

• Fielding, Roger A., et al. "Effects of prior exercise on eccentric exercise-induced neutrophilia and enzyme release." Medicine and science in sports and exercise 32.2 (2000): 359-364.
• Holmer-Jensen, Jens, et al. "Differential effects of dietary protein sources on postprandial low-grade inflammation after a single high fat meal in obese non-diabetic subjects." Nutrition journal 10.1 (2011): 1.
• Klop, Boudewijn, et al. "Understanding postprandial inflammation and its relationship to lifestyle behaviour and metabolic diseases." International journal of vascular medicine 2012 (2011).
• Krause, Eric G., et al. "Hydration state controls stress responsiveness and social behavior." The Journal of Neuroscience 31.14 (2011): 5470-5476.
• MacEneaney, Owen J., et al. "Effect of prior exercise on postprandial lipemia and markers of inflammation and endothelial activation in normal weight and overweight adolescent boys." European journal of applied physiology 106.5 (2009): 721-729.
• Peairs, Abigail D., Janet W. Rankin, and Yong Woo Lee. "Effects of acute ingestion of different fats on oxidative stress and inflammation in overweight and obese adults." Nutrition journal 10.1 (2011): 1.
• Pruimboom, Leo, et al. "Influence of a 10 days mimic of our ancient lifestyle on anthropometrics and parameters of metabolism and inflammation. The ‘Study of Origin’."

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.

Recent Studies Cast Shadow Over High Dose BCAA Intake: Increased Protein Wasting, Lower Brain Serotonin and More

Recent Studies Cast Shadow Over High Dose BCAA Intake: Increased Protein Wasting, Lower Brain Serotonin and More

amino acids anti-catabolic BCAA build muscle catabolism HDL insulin sensitivity isoleucine LDL leucine valine

To guzzle BCAAs all day or not - is that still a question or is the answer settled with the publication of two recent studies?

From previous SuppVersity articles about BCAA you will know that I don't buy into the hype supplement producers generate about the muscle-building and/or muscle-protective effects of high dose BCAA- or leucine-only supplementation.

One of the previously mentioned issues with BCAAs are their putative ill effects on neurotransmitter levels in the brain - effects that had only been observed in rodents, though. Now, a recent study in pigs, who are a much better model of human metabolism (even much better than most apes | Miller. 1987), is fueling the concerns about the pro-depression effects of high dose leucine supplementation.

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The corresponding study  (Wessels. 2016), which happens to have been sponsored by the BCAA producer Ajinomoto (quite ironic, isn't it?), sought to elucidate the response of high leucine diets on the activity of the BCAA metabolizing enzyme branched-chain keto acid dehydrogenase complex (BCKDH) and subsequent changes in the concentrations of free amino acids and amino acid derivates in several tissues, including the brain.

Figure 1: Brian tryptophan and serotonin levels in response to diets containing normal or two- (white) and four-fold (grey bar) elevated amounts of leucine (Wessels. 2016).

What the scientists found was a significant decrease in brain tryptophan with twice and a significant reduction of both brain tryptohan and serotonin levels with four times the regular amount of leucine in the piglets' diets (that's 1% vs. 2% vs. 4%). Bad news!? Well, 4% leucine in the diet are a very high amount with questionable practical implications. Even though the study confirms the potentially negative effects of the tryptophan blocking effects of leucine and BCAAs in general, the good think is that it assigns a relatively high number to the required dosage to see effects - whether lower doses would suffice to mess with all three BCAAs, as they were used by Choi et al. (2013), remains elusive, though.

In vivo comparison of the central action of isoleucine, valine, and leucine on glucose kinetics during pancreatic insulin clamps (Arrieta-Cruz. 2016).

It's not all bad news: While the potentially depression promoting effects of high dose leucine and the anti-anabolic / pro-catabolic effects of BCAA supplementa-tion in rodents are bad news, another recent study from the Mexican Ministry of Health supports the previously discussed anti-diabetic effects of isoleucine and sug-gests that valine may have similar effects. In view of the fact that the putative mechanism, for the increased glucose infusion rate (GIR | see Figure on the left) is an increased inhibitory effect of insulin on endogenous glucose production (EGP), not an increase in peripheral glucose utilization, it is yet questionable how relevant the results of Arrieta-Cruz' recent study in diet-induced o-bese rats are for athletes / healthy individuals for whom exuberant glycolysis / gluconeogenesis isn't a problem.

While it obviously depends on the severity of your BCAA addiction, whether the Wessels study is bad news for you, it is it is unfortunately too early to rejoice: More potentially bad news for BCAA junkies comes from a recent study by Milan Holecek et al. (2016) whose efforts to prove that diets containing extra BCAAs (valine, leucine, and isoleucine | HVLID), or a high(er) content of leucine (HLD) would have beneficial effects on the protein balance of rats in a two months study produced results neither the scientists nor I would have expected: In high doses BCAAs make your body waste protein!

Figure 2: BCAA content of the standard (SLD), high BCAA (HVLID) and high leucine (HLD) diets (Holecek. 2016).

Needless to say that this result is in diametrical contrast to what the scientists expected. Not only did Holecek et al. fail to demonstrate the expected positive effects of the chronic consumption of a BCAA- / leucine-enriched diet on protein balance in skeletal muscle. The results of their latest study actually "indicate rather negative effects from a leucine-enriched diet" (Holecek. 2015).

But BCAAs are muscle-builders how can leucine & co ruin protein synthesis? A reliable answer to this question has unfortunately yet not been found, but the results of the Holecek study suggest that an overabundance of BCAAs triggers an overexpression of the BCAA degrading enzyme BCKA dehydrogenase and the subsequent conversion of BCAAs to BCAA keto acids and / or eventually alanine or glutamine which are then (ab-)used as energy source by the liver (cf. modified figure from Holeček. 2001)

Instead of reducing the breakdown of protein, Holecek et al. found that a BCAA- or leucine-enriched diet tends to increase not just the breakdown of BCAAs, as well as the production of branch-chain keto acids (BCKA), alanine and glutamine and their utilization in visceral organs, it also impaired the rodent's protein synthetic response to a meal in postabsorptive state - particularly in fast-twitch (white) muscles.

Figure 3: Fractional rate of protein synthesis. Means ± SE, p < 0.05. *compared to the corresponding control (SLD or SLD + S); # compared to the corresponding fed group; † HLD (HLD + S) group vs. HVLID (HVLID + S) group (Holecek. 2016).

In spite of the fact that this increase in protein wastefulness, as I would call it, is bad news and the exact opposite of what the shiny BCAA ads and product write-ups promise, a significant loss in muscle weight was only observed in the soleus and ext. digitorum longus of the rodents in the high BCAA, but not the high leucine group. Accordingly, the study sheds a whole new light on the usefulness of BCAAs as 'muscle builders' or 'muscle protectors' and may, as Holecek et al. rightly point out...

"[...] explain the discrepancy between the protein anabolic effects of BCAA or leucine on muscles that were reported under in vitro conditions and/or shortly after BCAA intake and their reduced or lack of effects following chronic administration" (Holecek. 2016).

With the present study being conducted in healthy rodents without any of the condition that lead to muscle wasting (e.g. disorders like diabetes, or natural processes like aging) and in the absence of the stimulatory effect of exercise on signalling pathways that activate protein synthesis, future studies will have to determine, whether the ill effects on protein synthesis and increases in protein breakdown are (a) even more severe in muscle-wasting disorders, the elderly, and / or during endurance exercise, and how (b) the effects are modified by resistance training.

Figure 4: The previously not discussed ill (BCAA) and beneficial (leucine) effects of different levels of said amino acids on the HDL to LDL ratio of the rodents in the Holecek study should be taken into account, as well.

Bottom line: While the main outcomes of the two studies I discussed in detail in today's SuppVersity article do in fact cast a dark shadow on the health and performance benefits of BCAAs, it's not all bad news. Why's that? Here's why: (A) the Wessels study suggests that the amount of BCAAs that is required to produce practically significant reductions in brain serotonin is very high; (B) the significant reduction in the LDL/HDL ratio Holecek observed in the high leucine group of their study (Figure 4) and the lack of visible effects on actual muscle mass in the same group put the relevance of the increased protein breakdown in response to (at least) high dose leucine into perspective; and (C) there's still the Arrieta-Cruz study which shows that even isoleucine and valine of which the Holecek study draws a rather negative image, can have benefits - at least in the obese | Comment!

References:

• Arrieta-Cruz, Isabel, Ya Su, and Roger Gutiérrez-Juárez. "Suppression of Endogenous Glucose Production by Isoleucine and Valine and Impact of Diet Composition." Nutrients 8.2 (2016): 79.
• Choi S, Disilvio B, Fernstrom MH, Fernstrom JD. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines. Amino Acids. 2013 Aug 1. [Epub ahead of print] 
• FAO (Food and Agriculture Organization of the United Nations. "Food and nutrition in numbers." Rome, 2014; Food and Agriculture Organization of the United Nations.
• Holeček, Milan. "The BCAA–BCKA cycle: its relation to alanine and glutamine synthesis and protein balance." Nutrition 17.1 (2001): 70.
• Holeček, Milan, et al. "Alterations in protein and amino acid metabolism in rats fed a branched-chain amino acid-or leucine-enriched diet during postprandial and postabsorptive states." Nutrition & metabolism 13.1 (2016): 1.
• Miller, E. R., and D. E. Ullrey. "The pig as a model for human nutrition." Annual review of nutrition 7.1 (1987): 361-382.
• Wessels, et al. "Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model." PLoS ONE 11.3 (2016).

Cinnamon as Nutrient Partitioner and 1st-Line Treatment for Pre-Diabetes? 5% Decrease in Fasting Glucose per Month in Human Studies, Up to 24% in 40 Days W/ High(er) Doses

Cinnamon as Nutrient Partitioner and 1st-Line Treatment for Pre-Diabetes? 5% Decrease in Fasting Glucose per Month in Human Studies, Up to 24% in 40 Days W/ High(er) Doses

anti-diabetes cassia cinnamon cinnamon Coumarin diabesity diabetes fasting blood sugar glucose management HbA1c health insulin sensitivity lose fat

Yes, that's how real cinnamon look like. It does not grow as powder in plastic boxes on trees as I suspect the members of the generation McBurgerSubway believe ;-)

No, this is not absolutely new. In fact this is just "another" SuppVersity articles on the anti-diabetic effects of cinnamon, but I promise it's going to be the most comprehensive one. One that discusses the currently available evidence from human trials, as well as the things we know and believe to know about how cinnamon acts its anti-diabetic magic qualitatively and quantitatively.

Before I even go into further details, though, I would like to address one of the "cinnamon myths" that says that only the highly expensive Ceylon or Sri Lankan Cinnamon would do the trick, while the commonly sold Cinamon cassia would be useless or even dangerous due to its high (and in fact toxic) coumarin content.

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Interestingly, all human studies have been done with the "cheap toxic stuff from the supermarket". In view of what you are about to learn about its effects on blood glucose later in this article, the first take-home-message from today's article is thus: "Cheap cinnamon cassia will work just fine as a blood glucose management supplement!" Unfortunately, long-term studies the safety of "common cinnamon" with its highly variable coumarin content (0.31 g = harmless to 6.97 g = potentially dangerous per kg raw powder | Wang. 2013 | see Table 1) are non-existent.

Table 1: Content of Coumarin 1, Cinnamyl Alcohol 2, Cinnamaldehyde 3, Cinnamic Acid 4, Eugenol 5, Cinnamyl Acetate 6 in Cinnamomum Species and Commercial Samples (g/kg) | DUL = Detected under limits of quantitation; ND = not detected (Wang. 2013).

The only advise I can give you is thus to rely on supplements with standardized (low to non-detectable) amounts of this potentially carcinogenic substance (Wang. 2014) if you plan to take it regularly for years. Using the next best cinnamon powder from the supermarket next door on the other hand is probably not advisable even though some of the scientists who conducted the studies Arjuna B. Medagama reviewed for his (or her?) latest paper in Nutrition Journal (Medagama. 2015) probably did just that: Buy cinnamon powder from the supermarket next door to test its effects on blood glucose management in 40-days- to 4-months-studies in cinnamon-naive patients with (pre-)diabetes.

If you take a closer look at the data, though, it becomes obvious that some studies used plain cinnamon powder, while others used regular or commercial water-extracts (CinSulin. Anderson).

Effect of 6g of cinnamon on post-prandial blood glucose in healthy subjects (Hlebowicz. 2007). This hefty dose also slowed down gastric emptying and triggered non-significant increases in satiety in 14 healthy subjects after high CHO meals.

What's the optimal dosage? Even though the overview in Figure 1 suggests that "more helps more", Anand, et al. (2010) observed negative effects on the liver of rodents at dosages that would tantamount to ~40g of cinnamon per day. Ok, I assume you already apprehended that this is madness, but in the world of fitness maniacs and mad bodybuilders I thought it would be worth mentioning that even the coumarin free Ceylon cinnamon appears to have ill side effects when it is consumed in extremely high dosages. It would thus appear to be more reasonable to target an intake of 3-6 g of cinnamon with every major meal (it slows down gastric emptying and reduces postprandial blood glucose, therefore it makes sense to take it with a meal | Hlebowicz. 2007, see Figure to the left).

If you scrutinize the results I've plotted for you in Figure 1, you will notice that (a) the improvements in fasting blood glucose were significantly more pronounced than those of the long-term blood sugar maker HbA1c, that (b) the former appear to increase with the dosage that was used (Klan and Mang observed the highest reductions and used the highest amounts of cinnamon powder), and that (c) the reductions in HbA1c take time, i.e. several months and are not guaranteed, even if there are significant reductions in fasting blood glucose (cf. Belvins).

Figure 1: Relative changes in fasting blood glucose and HbA1c levels of pre-diabetic subjects (Medagama. 2015)

On average, the fasting blood glucose levels of the study participants in all studies decreased by 4.7% in four weeks; the HbA1c, on the other hand, by only 1%. Since part of the effects on blood glucose are merely a results of the reduced gastric emptying and will thus affect the peak values, yet not the overall glycemia, it appears logical that the HbA1c reacts slowly to the intervention. As Medagama points out, the effects of cinnamon are yet more far-reaching, so that more pronounced effects on the slow-reacting HbA1c levels can be expected to be seen in the hitherto non-existent long-term (= 1-2 year) studies, because cinnamon will also have ...

• 

  Figure 2: Molecular mechanisms of Cinnamon by which it exerts hypoglycaemic activity. (Medagama. 2015).

  direct effects on the insulin receptor have been observed for Cinnamtannin B1, a proanthocyanidin isolated from the stem bark of Ceylon cinnamon that activates the phosphorylation of the insulin receptor β-subunit on adipocytes as well as other insulin receptors,
• indirect effects on glucose management that are mediated by increased GLP-1 levels, a satiety hormone that decreases the amount of insulin that is necessary to clear glucose from your blood - as Medagama points out, probably by improving glucose transport,
• direct effects on the GLUT-4 glucose uptake receptor, the expression of which is increased by 42.8 % to 73.1 % in brown adipose tissue and muscle by cinnamon in a dose dependent manner,
• indirect effects on insulin sensitivity that are mediated by the effects of cinnamon on the expression of PPAR (α) and PPAR (γ), the increase of which is linked to increased glucose uptake - unfortunately, also in fat cells,
• direct effects on carbohydrate availability that are mediated by the inhibition of the amylase enzyme that is responsible for breaking down complex carbs into simple sugars,
• indirect effects on the endogenous production of glucose in the liver that is inhibited by cinnamon (glucogenesis, i.e. the storage of sugar in the liver, on the other hand, is promoted), and
• indirect effects that are brought about by the reduced rate of gastric emptying that will naturally slow down the absorption of glucose after a meal.

If that was too much for you to remember, I guess the graphical overview Medagama created may serve as a memory aid, when you come back to this article to refresh your knowledge about cinnamon and pre-diabetes. Speaking of which...

Glucose Control Beyond Carb Reduction ➲ Amino Acids, Proteins, Peptides | learn more!

So, what's the verdict about cinnamon and pre-diabetes? As Medagama points out in the conclusion to the previously referenced recently published review, "[b]oth true cinnamon and cassia cinnamon has the potential to lower blood glucose in animal models and humans" (Medagama. 2015). The problem is yet that we do not have reliable long-term safety studies for both, the problematic, potentially coumarin-laden regular cinnamon, as well as the expensive 99% coumarin-free Ceylon cinnamon, which has actually never been tested in human studies (rodent studies suggest that it works at least as well, though).

Addendum: As previously hinted at, there is no evidence from human studies that the "healthier", "true cinnamon" aka Ceylon cinnamon even works. Well, I just noticed that there's a single, rarely cited study in healthy individuals from the Lund University in Sweden that says that Ceylon cinammon has no effect whatsoever on glycemia and thus concludes "The Federal Institute for Risk Assessment in Europe has suggested the replacement of C. cassia by C. zeylanicum or the use of aqueous extracts of C. cassia to lower coumarin exposure. However, the positive effects seen with C. cassia in subjects w/ poor glycaemic control would then be lost." (Wickenberg. 2012)

To recommend regular cinnamon as a standard-supplement, you'd take everyday for years, on the other hand cannot really be recommended - not for pre-diabetics and by no means for healthy, active individuals who have no reason to take supplements with non-muscle specific glucose partitioning effects, anyways. If you want to improve your glucose management folks, work out - a glycogen-depleting strength or HIIT workout, that's the only scientifically proven muscle specific glucose repartitioner | Comment on Facebook!

References:

• Akilen, R., et al. "Glycated haemoglobin and blood pressure‐lowering effect of cinnamon in multi‐ethnic Type 2 diabetic patients in the UK: a randomized, placebo‐controlled, double‐blind clinical trial." Diabetic Medicine 27.10 (2010): 1159-1167.
• Anand, Prachi, et al. "Insulinotropic effect of cinnamaldehyde on transcriptional regulation of pyruvate kinase, phosphoenolpyruvate carboxykinase, and GLUT4 translocation in experimental diabetic rats." Chemico-biological interactions 186.1 (2010): 72-81.
• Anderson, Richard A., et al. "Cinnamon extract lowers glucose, insulin and cholesterol in people with elevated serum glucose." Journal of Traditional and Complementary Medicine (2015).
• Blevins, Steve M., et al. "Effect of cinnamon on glucose and lipid levels in Non–insulin-dependent type 2 diabetes." Diabetes care 30.9 (2007): 2236-2237.
• Crawford, Paul. "Effectiveness of cinnamon for lowering hemoglobin A1C in patients with type 2 diabetes: a randomized, controlled trial." The Journal of the American Board of Family Medicine 22.5 (2009): 507-512.
• Hlebowicz, Joanna, et al. "Effect of cinnamon on postprandial blood glucose, gastric emptying, and satiety in healthy subjects." The American journal of clinical nutrition 85.6 (2007): 1552-1556.
• Khan, Alam, et al. "Cinnamon improves glucose and lipids of people with type 2 diabetes." Diabetes care 26.12 (2003): 3215-3218.
• Mang, B., et al. "Effects of a cinnamon extract on plasma glucose, HbA1c, and serum lipids in diabetes mellitus type 2." European journal of clinical investigation 36.5 (2006): 340-344.
• Suppapitiporn, Suchat, and Nuttapol Kanpaksi. "The effect of cinnamon cassia powder in type 2 diabetes mellitus." Journal of the Medical Association of Thailand= Chotmaihet thangphaet 89 (2006): S200-5.
• Vanschoonbeek, Kristof, et al. "Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients." The Journal of nutrition 136.4 (2006): 977-980.
• Wang, Yan-Hong, et al. "Cassia cinnamon as a source of coumarin in cinnamon-flavored food and food supplements in the United States." Journal of agricultural and food chemistry 61.18 (2013): 4470-4476.
• Wickenberg, Jennie, et al. "Ceylon cinnamon does not affect postprandial plasma glucose or insulin in subjects with impaired glucose tolerance." British journal of nutrition 107.12 (2012): 1845-1849.