Can You Snort Caffeine? Is Shrimp Oil the Next Big Thing? Is Sweetener Acesulfame-K an AGE Reducing Superfood?

Coke Zero (31mg), Diet Coke (30mg), Diet Pepsi Jazz (21mg), Pepsi One (30mg), Diet Mountain Dew (18mg) and Sprite Zero (34mg) are your most prominent beverages that are sweetened with acesulfame-K (acesulfame-K content in mg per 12-ounce = 355ml can of soda).

Today's installment of the Short News will answer questions of earth-shattering importance. I mean, who wouldn't want to know if you can snort caffeine (and survive), can add shrimp oil to your list of goto-supplements and should start 'de-sugaring' your arteries with acesulfame-K, today? Ha...?

I see I've got your attention... that reminds me: If you have supplement questions of similar importance, let me know. It has been quite a while since I've addressed the last SuppVersity Reader Question here. About time to do another one... but for now, without further ado, here's the latest installment of the SuppVersity Short News.

You can learn more about coffee and caffeine at the SuppVersity

For Caffeine, Timing Matters! 45 Min or More?

Caffeine Helps When Taken Intra-Workout, too

Coffee can Help You Get into Ketosis

Post-Workout Coffee Helps With DOMS

Coffee Brewing 101 (Optimal Health)

Quantifying the Benefits of Caffeine on Ex.

• Shrimp oil, another waste product of the food industry gone health supplement that's useful for diet-induced diabesity treatment (Nair 2017) -- As a SuppVersity reader you know that some of the top-selling dietary supplements have long been considered waste. Whey, or fish oil, for example, are waste products the food industry didn't know how to dispose of for decades.
  
  With the publication of a recent paper in "Applied Physiology, Nutrition, and Metabolism", shrimp oil that is extracted from shrimp processing waste may join the ranks of the aforementioned waste-to-superfood supplements. In their study, the scientists from the National Research Council of Canada investigated the anti-obesity and anti-diabetes effects of shrimp oil in a rodent model of T2DM.
  

  

  Figure 1: Shrimp oil reduces the glucose surge during glucose tolerance test dose-dependently (Nair 2017).

  Male CD rats fed a high-fat diet (52 kcal% fat) and 20% fructose drinking water were divided into 4 groups and treated with the dietary replacement of 0%, 10%, 15%, or 20% of lard with shrimp oil for 10 weeks. Age-matched rats fed a low-fat diet (10 kcal% fat) were used as the normal control.
  

  

  Figure 2: Statistical sign. increases in markers of antioxidant status were observed only in the high dose group (Nair 2017). What would be interesting is to check if the same effects would be observed if the shrimp oil wouldn't be used to replace lard as in the study at hand, but a healthier oil, like a high MUFA olive oil.

  Rats on the high-fat diet showed impaired (p < 0.05) glucose tolerance and insulin resistance compared with rats fed the low-fat diet. Shrimp oil improved (p < 0.05) oral glucose tolerance, insulin response, and homeostatic model assessment-estimated insulin resistance index; decreased serum insulin, leptin, hemoglobin A1c, and free fatty acids; and increased adiponectin. Shrimp oil also increased (p < 0.05) antioxidant capacity and reduced oxidative stress and chronic inflammation.
  
  Omega-3s are almost certainly not the only active ingredient in shrimp oil 
  
  As Nair et al. point out, "[t]he antidiabetic benefits of shrimp oil might be attributed to its multiple bioactive components" - potential candidates to explain the benefits are (A) significant amounts of MUFA and n-3 PUFA, and (B) high concentrations of astaxanthin, vitamins E and vitamin A in shrimp, which will increase the antioxidant capacity and reduce oxidative stress. Overall, it is thus clear that shrimp oil has the potential to "dose-dependently improve [...] glycemic control", whether it works in humans, too, and if it's more or less effective than fish oil will yet have to be investigated in future studies, though.
  
  
  So what's the answer to the question from the headline? You better ask a psychic if it's going to be "the next big thing"; with its combination of healthy omega-3 fatty acids and antioxidants, it may be the price that decides if shrimp oil will follow fish oil, whey and the other waste products of the food industry and become a celebrated health supplement.

• There's no general effect of artificial sweeteners on AGE formation, and acesulfame potassium may, in fact, prevent the formation of advanced glycation end-products with all its unhealthy downstream effects (Ali 2017) -- There are dozens of purported health risks you supposedly expose yourself to when you consume sweeteners like saccharin, sucralose, aspartame, and acesulfame-K. One of the least researched of these purported side effects is the formation of amadori products (intermediates in the formation of AGEs) and advanced glycation end products (AGEs). The objective of a recent study from the University of Mumbai was to change that. Accordingly, Ali et al. investigated the influence of artificial sweeteners on the formation of AGEs and protein oxidation in an in vitro model of glucose-mediated protein glycation.
  

  

  Figure 3: Determination of carbonyl content of glycated lysine - in vitro model of AGE formation (Ali 2017).

  As the authors point out, their results indicate that the "above-mentioned artificial sweeteners do not enhance the process of glycation". But that's not all, in fact, Ali et al. found that acesulfame-K has anti-glycating potential "as it caused [a] decreased formation of Amadori products and AGEs" (Ali 2017).
  
  Now, this is just an in-vitro model study, and further studies are clearly necessary to be able to estimate the real-world relevance of the results. In spite of that, it is important to note that the study at hand supports the notion that replacing sugar, which - as a downstream effect of sugar-induced hyperglycemia - promotes the formation of AGEs with artificial sweeteners may reduce the diet-induced AGE burden significantly.
  
  
  So what's the answer to the question from the headline? While the word 'superfood' is clearly misplaced in the context of artificial sweeteners, it does indeed appear as if acesulfame-K, which is however used less frequently, these days, can actively reduce the formation of AGEs - in that, it is important to note, that its effects go beyond those of other sweeteners, the AGE-reducing effects of which depend on their use as sugar replacements.

• Yes, caffeine can be snorted, but no there's no magic to inspired caffeine powder (Laizure 2017) -- Depending on where you are on the "mad supplement junky"-scale you are either shaking your head now or cleaning your sinuses in excited apprehension. Wherever you are on said scale, though, you will probably be disappointed to hear that the magic many of us associate with the idea of snorting caffeine did not really work out in the real-world of the laboratory of the University of Tennessee Health Science Center, where S. Casey Laizure and colleagues used money from a grant by the National Institute on Drug Abuse to compare the pharmacokinetic disposition, cardiovascular effects, and subject perceived stimulant effects of a 100 mg dose of caffeine administered as an inspired powder using the AeroShot® device with the consumption of an equivalent dose by oral administration of an energy drink.
  
  For their study, the scientists recruited healthy men and women between the ages of 18 and 45 years - all of them moderate caffeine consumers (≤300mg / ~3 regular cups of coffee). Male and female non-smokers of any ethnicity were eligible to participate.
  

  

  Figure 4: As you can see the treatments had no significant effects on the cardiovascular parameters, even when the serum caffeine levels peaked - accordingly, there was no inter-group difference, either (Laizure 2017).

  The study was set up as a single center, two phase, crossover study: Each subject received 100 mg of caffeine by oral administration of an energy drink (Guru Lite®: caffeine in the form of guarana seed extract, and sweetened with stevia leaf extract) or inspiration of a fine powder into the oral cavity (AeroShot®: 100 mg of caffeine with 20 mg of vitamin B3, 2 mg of vitamin B6, and 6 µg of vitamin B12) on separate study days with at least a one week washout between phases.
  

  

  Figure 5: The results of the questionnaires on CNS-related parameters didn't differ, either, (a) between baseline and at maximal serum caffeine concentration and (b) between treatments (Laizure 2017).

  As you'd expect it from any good RCT clinical trial, the order of administration was randomly assigned, subjects were asked to refrain from consuming caffeine for 24 hours prior to their arrival at the lab in the morning, the breakfast (buttered toast and 2% milk) was standardized, and blood samples, heart rate, and blood pressure, as well as the subjects' self-assessed relaxation, alertness, jitteriness, tiredness, tension, and overall mood were assessed at standardized intervals.
  
  The dosages of powder and energy drink were chosen so that subjects would consume 100 mg of caffeine from both treatments (248 ml of Guru Light = 100mg caffeine and a single AeroShot container = 100mg of caffeine). Subjects were given a maximum of 5 minutes to consume the 100 mg caffeine dose.
  

  

  Figure 6: The pharmacokinetics of caffeine were virtually identical in both groups, only the peak differed with caffeine peaking earlier and at a higher concentration (1939 ng/L and 1790 ng/L at the peak for drink vs. snorted powder) in the energy drink trial. Accordingly, the AUC was greater for the drink, too (Laizure 2017).

  As you can see in Figures 4-6, the only significant inter-treatment differences could be observed in the pharmacokinetics of caffeine (Figure 6). Unlike some of you may have expected in view of the fact that "snorting caffeine" sounds so much more powerful than "drinking caffeine", the serum caffeine concentration in the energy drink trial rose faster and peaked at a higher level than it did in the snorting trial. Accordingly, the AUC, i.e. the total amount of caffeine that ended up in the bloodstream within those 8h after administration was 17569 ± 6869 ng/ml x h in the energy drink and only 15579±8387 ng/ml x h in the caffeine powder snorting trial.
  
  In spite of the slight differences in peak and AUC the caffeine profile and effects were, as the authors point out, "similar"; and I would go as far as to say "identical" - at least if we consider only practically relevant differences.
  

  

  Table 1: Comparison of caffeine pharmacokinetics of 100 mg of caffeine between different formulations; * Caffeine dose 160 mg. Cmax and AUC normalized to 100 mg caffeine dose. I have marked the "best" values for each parameter in green - and guess what: a simple coffee comes out on top in 3/4 categories.

  Ah, and if you take a closer look at Table 1 which show an the overview of maximal caffeine concentrations (Cmax), the time it took for those to be reached (Tmax), the total amount of caffeine that reached the blood stream within 8h (AUC), and the average half-life (t1/2) of administering 100mg of caffeine in form of either capsules, gums, energy drink, snortable caffeine, or hot coffee, you will realize: the good old coffee takes the "overall" (with the highest peak value, AUC and an only marginally lower Tmax, it is more than a compromise).
  
  
  So what's the answer to the question from the headline? Yes, you can snort caffeine, yes, it's probably safe, and yes, that sounds quite cool; but no, you cannot expect snorted caffeine to have a significant advantage over a simple cup of coffee - in fact, the available data suggest that the good old cup of hot coffee (heat will increase caffeine absorption) is still the king of caffeine 'vehicles'...  and I don't have to tell you about the additional health benefits (reduced T2DM, CVD, Parkinson's, Alzheimer's ... risk) of coffee, do I?

You like to learn a lot in a single SuppVersity article? Check out the June 2017 Coffee/Caffeine Research Update and learn more about caffeine.

What you're not happy with what you've learned today? I guess you want to know if you can snort chocolate, too, right?  Well, that's difficult to answer, because the guy who introduced Coco Loko, a snortable, allegedly energizing chocolate powder, to the market, Nick Anderson, came up with this ingenious (in marketing terms) idea before any mad scientist researched its effects in an RCT - in other words, there's no research to confirm its safety. Eventually, the powder is yet just the bastard child of chocolate and a naturally caffeinated (in this case guarana) energy drink.

If we look at the totality of research on energy drinks and pair it with the latest revelation that caffeine snorting is no better than a cup of coffee, we can reasonably argue that (a) this mix of organic cacao powder, gingko biloba, taurine, and guarana is probably relatively safe and marginally less effective than an energy drink or plain coffee with the same amount of caffeine | Comment!

References:

• Ali, Ahmad, et al. "Antiglycating Potential Of Acesulfame Potassium: An Artificial Sweetener." Applied Physiology, Nutrition, and Metabolism (2017).
• Kamimori, Gary H., et al. "The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers." International Journal of Pharmaceutics 234.1 (2002): 159-167.
• Laizure, S. C., et al. "Comparison of Caffeine Disposition Following Administration by Oral Solution (Energy Drink) and Inspired Powder (AeroShot) in Human Subjects." British Journal of Clinical Pharmacology (2017).
• Nair, Sandhya, et al. "Shrimp Oil Extracted from the Shrimp Processing Waste Reduces the Development of Insulin Resistance and Metabolic Phenotypes in Diet-induced Obese Rats." Applied Physiology, Nutrition, and Metabolism ja (2017).
• White Jr, John R., et al. "Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults." Clinical Toxicology 54.4 (2016): 308-312.