Want B12, But Hate Meat? Drink Milk! SNAC-Fortified Cyanocobalamin 136% More Bioavailable Than Standard B12 - Still Less Effective Than B12 From Cow's Milk

Figure 1: Milk still rules the
world (of B12 supplements ;-)

Vitamin B12 deficiency is probably more prevalent, than many people would have it. The water-soluble vitamin is most abundant in foods of animal origin and vegetarians (let alone vegans) are as much at risk of having inadequate B12 levels, as people with achlorhydria and, consequently, low intrinsic factor (an enzyme that requires an acidic environment to function and facilitate the utilization of B12 from foodstuff), or more generalized disturbances of the gastrointestinal structure due to aging (food-cobalamin malabsorption becomes increasingly prevalent after the age of 50), gastric resection, ileal resection, Crohn's disease, and bacterial overgrowth of the intestine. With vitamin B12 deficiency affecting cell division and precipitating to megaloblastic anaemia and neuropathy, close monitoring not only of vitamin B12 intake, but also of its proper utilization is of utmost importance for people belonging to one of the aforementioned groups.

Scientists from Emisphere Technologies in Cedar Knolls, New Jersey, have now come up with a new cyanocobalamin/SNAC coformulation, in which the sodium caprylic acid salt, N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC), a proven drug delivery agent, shall facilitate a more pronounced and more reliable absorption of orally supplemented vitamin B12 (Castelli. 2011). The formula, which contained 5-mg cyanocobalamin and 100-mg SNAC was administered to 6 human subjects in the fasted state in the form of 1 tablet, which had to be taken with 50 mL of water. Blood samples were taken at staggered intervals with the last blood draw taking place 24h after the ingestion of the B12/SNAC coformulation.

Figure 1: Time to and maximal serum concentration of B12 after oral administration or infusion of cyanocobalamine with and without SNAC; note: in order to compensate for the major differences between oral cyonocobalamine with and without SNAC a logarithmic scale was used (data adapted from Castelli. 2011).

As expected the concomitant administration of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) increased the meager biovalability of cyanocobalamine (which is absorbed really poorly, anyway) significantly:

Absolute bioavailability of B12 with the SNAC formulation was calculated from non–baseline-adjusted data to be 5.09% and was significantly greater (P < 0.05) than the commercial formulation (2.16%).

In view of the recently elucidated bioavailability of natural B12 from plain cow's milk (Matte. 2011), or should I say "liquid white gold", the 136% increase in bioavailability Christina Castelli and her coworkers achieved with their artificial combination of B12+SNAC appear quite ludicrous. 8%-10% that is the bioavailability et al. report in Jacques Matte and his colleagues from Canada report in their study on the bioavailability of vitamin B12 from cow's milk. Granted, this is a pig model, but other than rodents, which are usually used when it comes to studies, in which surgical interventions are necessary to elucidate the exact pharmacodynamics of a specific drug, pigs provide a very adequate model for the human gastrointestinal system, or as Miller and Ullrey already stated it in a 1987 paper on the "The Pig as an Animal Model For Human Nutrition" (Miller. 1987)

[...]with the possible exception of nonhuman primates, it is apparent that the omnivorous pig is one of the best models for study of nutrition issues in the omnivorous human.

This long established adequacy of the pig model of the human gastrointestinal tract has only recently been confirmed by Goulloteau et al. (Guilloteau. 2010). Matte et al.'s result that vitamin B12, which is naturally and abundantly present in cows’ milk, is more available at the intestinal level than the synthetic form - even if the latter is supplemented with SNAC - are thus very likely to apply to humans, as well.

Figure 2: Pharmacokinetics of vitamin B12 from different sources measured in pigs with an ultrasonic flow probe around the portal vein and a catheter inside the portal vein; values expressed as differences vs. unsupplemented animals; both values for cyanocobalamine alone are effectively 0, i.e not different from unsupplemented pigs (data adapted from Matte. 2011).

These results are also in accordance with retrospective studies in human subjects showing that vitamin B12 status is highly correlated with dairy product intake and studies on the absorption (absorption = entering the cells vs. bioavailability = becoming available in the blood stream) of vitamin B12 from dairy products in older men and women (>60y) by Robert M. Russel et al. (Russel. 2001), who report absorption of up to 65% for milk, which would be almost identical to the generally accepted absorption coefficient for meat products.

Note: Using a pig model Matte et al. were able to actually measure the portal-drained viscera (PDV) flux of vitamin B12, which provides more reliable results than radio-labelling studies, as they were used in Russel et al. It is thus all the more intriguing that the PDV for the unsupplemented diet or cyanocobalamin supplements [...] were not different from 0", or in other words - providing pigs with cyanocobalamine, which is the form of vitamin B12 that is used in most common dietary supplements, had no effect  on serum B12 concentrations, at all.

So, what does this tell you, after all? Well, let me phase it like that: If you have a Ferrari Enzo (milk and meat) waiting for you at the front door (in the fridge), wouldn't it be plain-out stupid to try to chip-tune (add SNAC) the family car (cyanocobalamine)? An the moral of the Story? Eat, don't supplement your vitamins!

Supplement Sensation? Oral Glutathione Supplements Dose-Dependently Double GSH in Randomized Controlled Human Studies. Health Implications Still to Be Determined

Blueberries and other foods w/ tons of polyphenols are GSH boosters (Moskaug. 2005) and make supplements obsolete. 

If you have been interested in dietary supplements for some time, I am pretty sure that you will have heard about oral glutathione ob(GSH) supplements in one of the "snake oil warnings" on various websites. The "master antioxidant" as it is called is after all believed by many to be not bioavailable - at least not orally. Studies in animal models, however, have already shown that oral GSH, administered either in the diet or by gavage, has the ability to increase plasma and tissue GSH levels ( Loven. 1986; Aw. 1991; Favilli. 1997; Kariya. 2007). It would thus be more appropriate to say that the efficacy of oral glutathione in humans has not yet been tested in peer-reviewed studies.

You can learn more about potential negative sides of too many / the wrong antioxidants:

NAC = GSH ￪, Anabolism ￬

Too Much "Vit C" For Gains?

Protein requ. of athletes

Block inflamma- tion, choke fire

C + E Get Avg. Joes Ripped

ROS Management Not Eradication

Now, the absence of human studies should definitely ring an alarm bell in the head of every healthily skeptic supplement user, what it should not do, though is mislead you to believe that GSH supplements don't work in human beings.

Now this is where John P. Richie Jr. and his colleagues from the Penn State Cancer Institute, the Department of Microbiology and Immunology at the Penn State University College of Medicine and the Orentreich Foundation for the Advancement of Science, come into play. As the scientist state, their "objective was to determine the long-term effectiveness of oral GSH supplementation on body stores of GSH in healthy adults." (Richie. 2014)

Warning - keep an eye on your wallets: Even if the supplements work, they are probably going to be expensive and in view of the fact that "the increases were dose and time dependent, and levels returned to baseline after a 1-month washout period" (Richie. 2014), you will (a) have to take plenty to achieve maximal effects and (b) do that year-round. In view of the fact that we still don't have evidence of any downstream health benefits, I would thus be hesitant to recommend buying a GSH supplement at the moment - specifically if you are healthy, eat clean and work out!

To this end, they conducted a 6-month randomized, double-blinded,placebo-controlled trial in the course of which the subjects, 41 women and 13 men (6 dropouts not included) with a normal BMI and no known health issues, consumed either ...

• an oral GSH supplement dosed at 250mg/day,
• an oral GSH supplement dosed at 1,000mg/day, or
• an identically looking placebo.

The main study outcomes were obviously analyses of the GSH levels in (a) blood, (b) erythrocytes, (c) plasma, (d) lymphocytes and (e) exfoliated buccal mucosal cells (the effects on a battery of immune markers was tested only in a handful of subjects).

Figure 1: Effects of 6 months GSH supplementation on ratio of oxidized to reduced GSH and natural killer cell cytotoxicity in healthy men and women aged 28-72y (Richie. 2014)

As the data in Figure 1 already suggests, there was a dose-dependent increase in GSH levels. With the high dose (1,000mg/day) producing GSH increases of 30–35 % in erythrocytes, plasma and lymphocytes and 260 % in buccal cells (P<0.05) and increases of 17 and 29 % in blood and erythrocytes, respectively, in the low-dose group (P<0.05 - data not shown in Figure 1).

These improvements had beneficial downstream effects on the overall status of the subjects' antioxidant defense system. A fact you can conclude based on the decreased ratio of oxidized (used) to reduced (fresh) glutathione in whole blood the scientists observed in their subjects after 6 months. These benefits came hand in hand with an increase in natural killer cytotoxicity (+100%), another potentially highly desirable health benefit.

Inflammatory cytokines won't build muscle. Without them, however, your body won't notice that it's time to adapt and w/ too much glutathione just that could happen.

Bottom line: The fact that they obviously are bioavailable and have potent antioxidant and immune-strengthening effects make glutathione supplements particularly attractive for anyone who is suffering from chronic inflammation (obesity, diabetes, or both) and/or taking anti-inflammatory, but immune suppressive drugs (autoimmune diseases from simple allergies over asthma and rheumatism to multiple sclerosis).

Whether you, the not-so-average SuppVersity reader will feel, let alone see any benefits from using these supplements is in my humble opinion highly questionable. And in case you've already forgotten about the Janus-faced effects the GSH-booster N-acetyl-cysteine will have on training induced muscle injury, cytokine expression and anabolic signalling, I'd suggest you take another look at an almost 12-months old follow-up to the SuppVersity Science Round-Up.

References:

• Aw, Tak Yee, Grazyna Wierzbicka, and Dean P. Jones. "Oral glutathione increases tissue glutathione in vivo." Chemico-biological interactions 80.1 (1991): 89-97.
• Favilli, Fabio, et al. "Effect of orally administered glutathione on glutathione levels in some organs of rats: role of specific transporters." British journal of nutrition 78.02 (1997): 293-300.
• Kariya, Chirag, et al. "A role for CFTR in the elevation of glutathione levels in the lung by oral glutathione administration." American Journal of Physiology-Lung Cellular and Molecular Physiology 37.6 (2007): L1590.
• Loven, Dean, et al. "Effect of insulin and oral glutathione on glutathione levels and superoxide dismutase activities in organs of rats with streptozocin-induced diabetes." Diabetes 35.5 (1986): 503-507.
• Moskaug, Jan Ø., et al. "Polyphenols and glutathione synthesis regulation." The American journal of clinical nutrition 81.1 (2005): 277S-283S.
• Richie Jr, John P., et al. "Randomized controlled trial of oral glutathione supplementation on body stores of glutathione." European journal of nutrition (2014): 1-13.

True or False: Vinegar Reduces Postprandial Glycemia And Insulin Response. Vitamin D Must Be Taken With Fat or It Won't Work. Chewing Gum Will Help You Get & Stay Lean

This is quite an extraordinary Wednesday! To make sure that you don't have to go without your beloved Science Round Up, Carl and I are doing the show one day early, which means that you better make sure to make some room for listening to the show at 1PM EST (listen live!), if you want to be the first to learn the truth about the

Is it possible that your significant other outpaces you on all cardio activities, because she has the hormonal edge?

• effects of soy protein supplementation on the endocrine effects of exercise
• psychological effects of performance enhancing drugs & supplements
• interaction between dietary salt & your bodies ability to store magnesium
• vitamin D "dosage equivalent" of two tanning bed sessions per week
• estrogen's fat burning prowess
• better (?) alternatives to testosterone gel

... and all the other great topics, you will be able to listen to after you've witnessed Alex aka Primalkid's premier (what an alliteration) as SuppVersity guest author. I suppose that most of you will already have noticed that he helps me more than just "a lot" by answering questions in the comment section. Oftentimes these are pretty individual things, but sometimes they are downright "True or False"-compatible - just as the mini-article on Vinegar, Alex sent me a couple of days ago.

Vinegar Helps Reduce Postprandial Glycemia and Insulin Spike

True (minimally edited answer written by Alex aka Primalkid) Recently, apple cider vinegar has earned merit as a health tonic. No longer sold solely as a condiment in grocery stores, more and more people see apple cider vinegar as a remedy. Its wide availability and affordability make it appealing to those who have browsed the Internet, read various diet books, or even read the label on the bottle, all of which make fame of its weight loss ability. But is there any truth about those "rumors" or do they belong to the same class of "repeat it until everyone believes it must be true" gems of dietary wisdom like the notion that "fat will reduce the insulin spike from a carby meal" (learn more about this one in the previous of "True or False")

The discussion following last week's installment of "True or False", particularly about the way generations of dieters have been fooled to believe that it was a good idea to drown your carbs in fat in order to minimize the insulin spike was probably the incentive for Alex to author his first (and maybe not last) SuppVersity article... well, a part of an article ;-)

A 2006 review of all relevant epidemiologic studies and clinical trials found that "many recent scientific investigations have documented that vinegar ingestion reduces the glucose response to a carbohydrate load in healthy adults and in individuals with diabetes" (Alex' emphasis in Johnston. 2006). The review also concluded that "vinegar ingestion increases short-term satiety."

A fairly recent randomized controlled trial seeking to investigate if a combination of cinnamon and vinegar would have an additive blood glucose-lowering or satiety-enhancing effect compared to the substances in isolation, however, "did not see an effect of acetic acid on blood glucose" (Mettler. 2009). The study consisted of 27 non-smokers 20 to 30 years old with normal BMI and fasting blood glucose. In other words, they may be considered healthy adults. The control meal consisted of 194g vanilla milk rice and 33g glucose dissolved in water, providing a total of 75g carbohydrates, 5g fats, and 7g protein, and was consumed after an overnight fast of at least ten hours.

The researchers concluded that "the most apparent difference between the studies was the food matrix with which the acetic acid or vinegar was ingested," and admit ignorance as to why the vinegar might work more or less in different contexts.

Table 1: Tabular overview of the design of the four trials in the 2010 study by Johnston et al.

Fortunately, the answer comes three months later when a group of researchers at The College of Nursing and Health Innovation sought to investigate the dosage, timing and application of vinegar for reducing postprandial glycemia (PPG) (Johnston. 2010). This study recruited both healthy and type-2 diabetic individuals, and had them consume either a meal (white bagel, 20g butter, 200g juice) or a glucose drink after a ten to 12 hour fast in four different trials.

• Trial one examined whether small amounts (2 – 20g) of vinegar had any glycemic effects.
• Trial two sought whether this effect persisted for five hours after consumption of the vinegar.
• Trial three looked at whether the type of carbohydrate influenced vinegar’s antiglycemic effect.
• Trial four looked at whether the neutralized salt of acetic acid was effective in diabetics.  

One detail I want to bring to your attention pertains trial 3 and could in fact explain why other studies failed to observe an antiglycemic effect of vinegar: In Mettler’s study, the control meal consisted of milk rice and a dextrose solution, both of which can safely be classified as "simple" sugars.

So, Johnston’s research suggests that the antiglycemic effect of vinegar is best realized when ingested with foods composed of complex carbohydrates and that vinegar may not attenuate PPG following the consumption of foods sweetened with corn syrups or dextrose, as is the case for many processed beverages and foods.

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Bottom line: Aside from the fact that the last mentioned limitation implies that taking your vinegar with junk food is pointless, it appears that apple cider vinegar may in fact earn a place among the list of truly "functional" foods. And while the real-world benefits may be more pronounced for people who do already have slightly suboptimal (or worse ;-) insulin sensitivity, a small amounts of vinegar (2tsp - doesn't really matter which type) taken with a whole foods based meal may be considered one out of many proven dietary manipulations for reducing PPG. 

No Fat No Vitamin D - Fat's Necessary to Benefit from High Dose Vitamin D

Probably false. I know that you will now be citing an older post of mine discussing a study that showed quite conclusively that the usage of supplemental vitamin D is hampered, if it is not ingested with a significant amount of dietary fat (see "A Fat D-Ficiency").

Now, a soon-to-be-published paper by a group of scientists from the Human Nutrition Research Center on Aging at Tufts University and the Division of Endocrinology, Diabetes, and Metabolism at the Tufts Medical Center put a huge question mark after the results of the 2011 study by Raimundo et al. who had used an almost identical protocol in 20 likewise healthy subjects.

Figure 1: Changes in serum vitamin D3 and storage form of D3 (25OHD, small grey-scale graph) in response to 50,000 IU of vitamin D with / without a meal with high or low fat content (Dawson-Hughes. 2013)

As you can see in figure 1, the low fat meal did yield an even more rapid incline in plasma vitamin D3 levels, after the 90-day follow-up period the net "gain" in terms of serum 25OHD was yet identical in all three groups and brought the sixty-two 50-69 yrs subjects who were enrolled in this 3-month study well into the >70 nmol/L range for 25OHD - and that irrespective of whether they had ingested their D3 tablet** on empty or with an egg or egg white frittata with low or high amounts of olive oil and vegetables, turkey bacon, and Parmesan cheese topping, a slice of toast with either jelly (low-fat meal group) or butter, and a mango milk smoothie (mango, milk, ginger ale) with or without cream.

Foods & the Sun are the natural vitamin D sources, listen to today's Science Round Up to learn more about the latter.

** Note: I mentioned this before on the Science Round-Up: You better don't put too much faith into what the label of your D3 supplement says. Even with the supplement used in the study (50,000 IU vitamin D3 tablets that were purchased from BioTech Pharmacal) there was a >10% difference between what the label said the tabs would contain (obviously 50,000IU) and the measured amount of 57,000 IU of vitamin D3 the tabs actually contained. In the aforementioned study by Garg et al,. one of the tested vitamin D3 tabs contained more than twice of the labeled amount (Garg. 2013).

Just like Dawson-Hughes and colleagues, I can only speculate about the underlying reasons for the differences between the study at hand and the Raymundo study. The scientists' hypothesis that the unexpectedly high and early increase in the high fat (25.6g) group of the study by Raimundo et al. could be attributable to "inadvertent sun exposure or supplemental vitamin D ingestion in the second half of that study", would yet be a plausible explanation. Another one could be the use of cabs instead of tabs, as they were used in the study at hand. After all, the content of the 50,000IU vitamin D cap Raimundo et al. have used is like to be released much more rapidly so that the fat may have been necessary to slow the gastric emptying and thus facilitate absorption.

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Bottom line: For you it does not really matter if you can ingest your vitamin D without fat. It's not the "better" alternative, so why would you bother anyway? So have it with a fatty meal, but don't forget that testing is not optional, but obligatory - I mean you do not even know how much vitamin D your Vitamin D product actually provides.

Chewing gum Helps to Get & Stay Lean (Note: This is just about regular chewing gum!)

True.  I know it may sound hilarious, but in view of the fact that research has shown "gum chewing is sufficiently exothermic that if a person chewed gum during waking hours and changed no other components of energy balance, a yearly loss of more than 5 kg of body fat might be anticipated." You can certainly argue that chewing of calorie-free gum, of which James Levin points out that it "can be readily carried out throughout the day", the "potential effect on energy balance should not be discounted" (Levin. 1999).

Mint chewing gums are incompatible to the "6x Bananas a Day!?" approach to lowering your glucose, insulin and HbA1c levels (learn more)

Chewing mint gums will reduce fruit consumption (Swobody. 2013) -- Why? Give it a try, I bet you will not recognize the delicious pineapple when you try to eat it right after you've been through a packet of Orbit Mint ;-) This may sound like it was not important, but it could in fact diminish or even blunt the effects of chewing gum... I mean think of Mr. Average Obese American at a barbecue. If he had not been chewing mint-flavored gum all the time, he may well have had his share of filling, refreshing & libido enhancing water melon before the barbecue was even ready to be served. Now that he missed on that, he will stick to the meat (+) and tons of salty junk (-). Not a good bargain, right?

Now, all of you know that I am no fan of the "calories in vs. calories out"-hypothesis Levin is referring to, here, but in view of the fact that chewing (sugar free!) gum has also been shown to

• 8% reduced food intake on a "snack break" and generally reduced cravings and perceived likelihood of snacking on sweet foods in 40 women and 20 men (21.7+/-4 years; BMI=22.7+/-3.4) who participated in a 2007 study at the Glasgow Caledonian University) who came to the laboratory four times for lunch and then returned 3 h later for a snack after either chewing gum or not chewing gum for 15 minutes before the snack break (Hetherington. 2007). 
• chewing gum will reduce the size of snacks even in moderately restraint eaters, although the effect is not as pronounced as it is in people who are not thinking about what and how much they are eating all day (Hetherington. 2011)

So, in general, it is probably advantageous to chew gum. The probability that it will result in significant weight loss is however small. A 2012 one of those pathetic randomized controlled trials, in the course of which the researchers provide their subjects with dietary advice and expect something to happen, the 102 of the 201 overweight and obese adults who were furthermore required to chew gum for at least 90min/day did not lose significantly more body weight or inches off their waist. Contrary to their non chewing gum chewing peers in the control group there was a greater heterogeneity so that only the difference to baseline reached statistical significance only in the chewing gum group.

If there is anything bad to say about chewing gums it would probably pertain to the (imho) not fully elucidated side effects xylitolm a proven "antimicrobial" (Mäkeläinen. 2007), could theoretically have on the gut microbiome, but since we do not know if that would be a detrimental and not even a beneficial effect (initial evidence exists, cf. Salminen. 1985), I just want to mention it as an "would be interesting to see more research in this direction". Possible artificial sweetener related distortions of the hedonic response to sweet foods, on the other hand, are not very likely... well, as long as you stick to the spearmint and peppermint varieties and refrain from those disgustingly sweet fruit gums.

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There may be more advantages of chewing gum. People with GERD / reflux disease, for example have been shown to benefit from chewing gum for 1 h after the meal. The effect lasted for up to 3 h and occured in both patients with and without chronic reflux disease (Avidan. 2001). Chewing gum has also been shown to reduce the symptoms of depression (Erbay. 2013), alleviate acute psychological stress (Scholey. 2009), and increase alertness on "intellectual" performance during regular intelligence tests (Smith. 2009; similar effects in previous studies with sugar- and artificially sweetened gums, cf. Stephens. 2004)

Bottom line: The Shikany study is actually a perfect example of what chewing gum can do for the average dieter. Although it overall effects on caloric expenditure are non-significant the act of chewing and what my friend Carl Lanore once aptly called "cleaning one's pallet" with a sugar-free peppermint gum can help you (a) not to return to the buffet, once you've decided that you've had enough and started chewing gum and (b) not grab another snack between your main meals.

Against that background, the statement "chewing gum can help you lose weight" is actually correct. What is yet a hilariously unrealistic expectation is that you would - just like Levin mentioned it in the initially cited letter to the editor - be able to lose X pounds of pure body fat per year, because chewing gum increased the caloric expenditure of the subjects in the Levine study by 12kcal per hour.

That's what people in Germany call a "Milchmädchenrechnung" or as you would call it, my dear American friends, "naive fallacy" - a type of naive fallacy which is unfortunately still pretty common especially among people who make not one, but two major mistakes and don't read the SuppVersity and listen to Super Human Radio ;-)

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That's it for the written part (don't miss the Science Round Up at 1PM EST, though!), I hope you enjoyed this installment of True or False and though I will be hard pressed to answer all the questions, just keep the suggestions coming. I will take the weekend to compile a detailed list to make sure I don't overlook any of them, when I tackle at least one of your suggestions in the future installments of this series.

References:

• Avidan B, Sonnenberg A, Schnell TG, Sontag SJ. Walking and chewing reduce postprandial acid reflux. Aliment Pharmacol Ther. 2001 Feb;15(2):151-5.
• Dawson-Hughes B, Harris SS, Palermo NJ, Ceglia L, Rasmussen H. Meal conditions affect the absorption of supplemental vitamin D(3) but not the plasma 25-hydroxyvitamin D response to supplementation. J Bone Miner Res. 2013 Feb 20.
• Erbay FM, Aydın N, Satı-Kırkan T. Chewing gum may be an effective complementary therapy in patients with mild to moderate depression. Appetite. 2013 Jun;65:31-4.
• Garg S, Sabri D, Kanji J, Rakkar PS, Lee Y, Naidoo N, Svirskis D. Evaluation of vitamin D medicines and dietary supplements and the physicochemical analysis of selected formulations. J Nutr Health Aging. 2013 Feb;17(2):158-61.
• Hetherington MM, Boyland E. Short-term effects of chewing gum on snack intake and appetite. Appetite. 2007 May;48(3):397-401.
• Hetherington MM, Regan MF. Effects of chewing gum on short-term appetite regulation in moderately restrained eaters. Appetite. 2011 Oct;57(2):475-82.
• Johnston CS, Steplewska I, Long CA, Harris LN, Ryals RH. Examination of the antiglycemic properties of vinegar in healthy adults. Ann Nutr Metab. 2010;56(1):74-9. 
• Johnston CS, Gaas CA. Vinegar: medicinal uses and antiglycemic effect. MedGenMed. 2006 May 30;8(2):61.
• Levine J, Baukol P, Pavlidis I. The energy expended in chewing gum. N Engl J Med. 1999 Dec 30;341(27):2100.
• Mäkeläinen HS, Mäkivuokko HA, Salminen SJ, Rautonen NE, Ouwehand AC. The effects of polydextrose and xylitol on microbial community and activity in a 4-stage colon simulator. J Food Sci. 2007 Jun;72(5):M153-9. 
• Mettler S, Schwarz I, Colombani PC. Additive postprandial blood glucose-attenuating and satiety-enhancing effect of cinnamon and acetic acid. Nutr Res. 2009 Oct;29(10):723-7. 
• Salminen S, Salminen E, Koivistoinen P, Bridges J, Marks V. Gut microflora interactions with xylitol in the mouse, rat and man. Food Chem Toxicol. 1985 Nov;23(11):985-90.
• Scholey A, Haskell C, Robertson B, Kennedy D, Milne A, Wetherell M. Chewing gum alleviates negative mood and reduces cortisol during acute laboratory psychological stress. Physiol Behav. 2009 Jun 22;97(3-4):304-12. 
• Smith A. Effects of chewing gum on mood, learning, memory and performance of an intelligence test. Nutr Neurosci. 2009 Apr;12(2):81-8.
• Shikany JM, Thomas AS, McCubrey RO, Beasley TM, Allison DB. Randomized controlled trial of chewing gum for weight loss. Obesity (Silver Spring). 2012 Mar;20(3):547-52.
• Stephens R, Tunney RJ. How does chewing gum affect cognitive function? Reply to Scholey (2004). Appetite. 2004 Oct;43(2):217-8; discussion 221-3.
• Swoboda C, Temple JL. Acute and chronic effects of gum chewing on food reinforcement and energy intake. Eat Behav. 2013 Apr;14(2):149-56.

Victorious Veteran: Creatine Monohydrate Still First Class! Usefulness & Safety of “Innovative” Creatine Formulas Questionable.

If we discount a high protein intake as a regular constituent of a healthy diet, creatine is unquestionable the King of Natural Ergogenics. Its impact on athletics way beyond the Gold’s Gyms of the bodybuilding world is evident from its being cited as “effective and safe” in almost each and every “position stand” published in one of the journals of the various sports & nutritional societies all over the world in regular intervals. Thus, with the (nephro-)toxity myth being finally dispelled, creatine has become a stable in the supplement regimen of both recreational, as well as professional athletes.

Now, the financial revenue you can make from a non-patentable amino acid that is commonly found in fish and meat products is obviously limited. Thus, the steadily increasing number of players on the supplement market is continuously trying to “reinvent the wheel”, by putting forward a new, better-absorbed, more effect, side-effect free or whatever else the marketing guys had on their minds forms of N-(aminoiminomethyl)-N-methyl glycine (=chemical formula of creatine). These “superior” forms of creatine are then put forward as the must have for every seriously training athlete and/or creatine non-responders (these are people, where – due to various not fully understood mechanisms – creatine has no measurable effect on performance, (intracellular) water retention and body weight) and usually disappear from the market just about at the same time, the first batch has been sold and disappointed customers begin to vent their anger on the blogs and bulletin boards of the fitness world.

With reference to the purported superiority of novel forms of creatine R. Jäger, one of the leading researchers in the field writes in a recently published paper (Jaeger. 2011), the results of which have previously been presented at the 2010 Creatine in Health and Sports conference:

[…] the efficacy, safety, and regulatory status of most of the newer forms of creatine found in dietary supplements have not been well established. Additionally, there is little to no evidence supporting marketing claims that these newer forms of creatine are more stable, digested faster, and more effective in increasing muscle creatine levels and/or associated with fewer side effects than CM.

In their extensive review of the literature Jäger et al. dissect many of the commonly held views on the purported “instability” and “low absorbtion rate” of creatine monohydrate, evaluate the different creatine contents of various supplemental forms and their individual solubility, stability and bioavailability. And while some other forms are in fact more soluble…

Creatine monohydrate dissolves at 14 g/L at 20°C resulting in a neutral pH of 7. A saturated solution of tricreatine citrate in water has a pH of 3.2; whereas a saturated solution of creatine pyruvate even has a pH of 2.6 (pyruvic acid is a stronger acid than citric acid). The decrease in pH results in an increase in solubility: 29 g/L creatine citrate at 20°C, and 54 g/L creatine pyruvate at 20°C. Normalized by the relative amount of creatine per molecule (monohydrate 87.9%, citrate 66%, pyruvate 60%), creatine citrate (19.14 g/L) shows a 1.55-fold and creatine pyruvate (32.4 g/L) a 2.63-fold better solubility when compared with the monohydrate (12.3 g/L).

The acidity of your stomach is high enough, anyway, so that even if you just swallow the powder it will eventually dissolve, when it comes in contact with your gastric acid - for monohydrate [CM] Jaeger reports the absorption to be as high as 99%.

Furthermore, pre-solving of creatine in water is counter-indicated, because, as Jaeger et al. write, …

[…] solution precludes the manufacture of shelf-stable standard ingredient. If creatine is not consumed immediately after it has been dissolved in water, it should be stored at a low temperature to retard the degradation.

So you better throw away your liquid creatine - chances are its 99% degraded even before you bought it from your retailer.

The instability is even more of concern in the case of Creatine Ethyl Ester (CEE) which has been found to be “actually less stable than CM.” (Child & Tallon. 2007).

CEE is mostly converted into creatinine under physiological conditions encountered during transit through the various tissues, suggesting no ergogenic effect is to be expected from supplementation of CEE.

The latter, i.e. creatine ethyl esther, is also less bioavailable, 

Figure 1:Changes in total muscle creatine content in response to placebo (PLA), creatine monohydrate (CRT), and creatine ethyl ester(CEE) supplementation (Spillane et al. 2009, cf, fig. 1).

and studies (Spillane. 2009) suggest that its higher rate of degradation to creatinine may pose a possible health risk.

Also, while Jaeger et al. report some evidence for the beneficial effects of co-supplementation with glucose, protein or (low dose) D-pinitol, I personally doubt that either of them is necessary to take advantage of the repeatedly proven ergogenic effects you can get from the cheapest, most researches, safest and easiest to obtain form of creatine – creatine monohydrate.

On a side note: My friends @ironmagazine.com have found an interesting study on the effect of creatine + nitrate, which is currently hyped as “the next big thing”. Although, I suppose that the amount of the carcinogen N-nitrososarcosine, which is a byproduct of their reaction, is hardly high enough to trigger cancerous growth, the lack of direct scientific evidence that creatine nitrate has any beneficial effect over the individual use of nitrates (for pump) and creatine (for performance) at least makes me wonder if you could not eat a buckload of beet roots (high in nitrate) with your creatine monohydrate to achieve the same effect ;-)