Sunday, June 3, 2012

Whey More Insulinogenic Than White Bread: Insulin Spike is Mediated by GIP Secretion in the Gut & Effect of EAAs on the Pancreas + Why Whey is Still the Better Choice

Image 1: Peter Czerwinski, aka Furious Pete, certainly did not care about the pro-insulinogenic effects of whey, when he ate 900g of it within 3:30min, click here to watch his record (Furios Pete, 2010)
Among muscle heads and physical culturists, alike, whey protein has become almost synonymous with building slabs of lean muscle.What many of the protein fans - especially the low carbers - tend to overlook or ignore, though, are the pro-insulinogenic effects of whey protein, in general, and purified whey protein isolates and hydrosolates, in particlar, which do not just augment the insulin release in response to carbohydrate ingestion (Morifuji. 2010), but exert a decent increase in pancreatic insulin release in and out of themselves (Claessens. 2009). Further evidence on the hitherto not yet fully understood mechanism behind the whey induced increase in insulin comes from a recently published paper by Albert Salehi and his colleagues from the Lund University in Sweden, the University of Copenhagen in Denmark and the Oxford Center for Diabetes, Endocrinology and Metabolism in the UK (Salehi. 2012).

Whey vs. white bread and human plasma as incubation medium

In the aforementioned paper, the scientists present the results of a combined in-vivo + in-vitro trial on the effects of glucose, amino acids and amino acids mixtures (as they are found in whey) on pancreatic insulin production and its relationship to the incretin response (release of incretin hormones from specialized cells in the small and large intenstine). To this ends, the researchers had their subjects, four men and two women (healthy non-smokers, normal-weight, age 20-30y), consume test meals containing either white bread (3.7g of protein) or whey (16.7g of protein), after an overnight fast, on two different occasions. The meals had to be consumed within 12 minutes and blood samples were taken 7.5,  15, 30 and 45 min after the start of the meal.
Figure 1: GIP and GLP-1 response to whey and white bread (left, top & bottom); insulin release (%) per islet relative to glucose after incubation with different amino acids, amino acid mixtures and mixture + GIP (Salehi. 2012)
As you can see in figure 1 (left), the ingestion of  ~20g of whey protein (containing 16.7g of protein + lacose + minimal amounts of fat) produced a significantly more pronounced in increase in glucose-dependent insolinotropic peptide (GIP, see previous post "Waxy Maize Reloaded" for more information) than the white bread meal. GIP is a hormone-like substance that is produced by the enteroendocrine cells of the gut lining, amplifies the glucose-induced production of insulin in the pancreas, slows down digestion, increases glucose absorption, ramps down fatty acid oxidation and sets you into energy "storage mode" - unfortunately in both forms, skeletal and liver glycogen and fat!
Figure 2: Simplified schematic illustration of mechanism behind the EAA induced GLUT-4 increase in skeletal muscle (click here to learn more)
GLUT-4 activation - another reason, why whey is way better than sugar: If you remember Monday's blogpost on the isolated effects of essential amino acids (EAAs) on the GLUT-4 (glucose transporter = the shuttle that carries glucose from the blood stream into the cell) expression on skeletal muscle cells, it is evident that contrary to sugar or most forms of carbohydrates, whey protein, or rather the essential amino acids in whey, cod, soy, beef, pea, egg and other high EAA protein sources exert nutrient-repartitioning effects due to selectively increasing insulin induced glucose uptake in skeletal muscle and constant glucose uptake in adipose tissue (Lavigne. 2001).
Against that background it is not surprising that the combined effects of GIP (figure 1, top-left) and the amino acid induced increase in insulin production (figure 1, right, orange) lead to a more than 7-fold increase (compared to glucose control) in pancreatic insulin production after incubation of mouse Langerhans cellls (the cells of the pnacreas that are responsible for insulin mediated glucose control) with sera containing a mixture of EAAs and GIP that was matched to the respective EAA and GIP concentrations in the preceding whey vs. white bread human experiment.

Don't worry there are also benefits that can compensate for the insulin spike

Now these results certainly seem odd, after all "the experts" say that insulin is the root cause of all evil! Now whey spikes insulin and GIP and still we see study after study popping up, reporting "beneficial effects" of whey protein on glucose metabolism and overall health - how can that be? The reasons are manifold and actually quite straight forward:
  1. Insulin is not the devil - Contrary to common believe the problem is not insulin, but insulin resistance and overspilling glucose stores. If your insulin spikes and you are not insulin resistant, the cells will suck up glucose, your blood sugar will drop and your insulin will drop as well; so, in terms of negative side effects, the most obvious one would be postprandial hypoglycemia in response to large boluses of whey protein (and even that is usually compensated for by increases in glucagon and consequently gluconeogensis)  - that the latter can have long-term detrimental effects on insulin sensitivity is a whole other issue, though...
  2. Many studies use (pre-)diabetic subjects - In a pre-diabetics an increase in insulin release due to whey will improve postprandial glycemia and must thus be considered beneficial - it's "nature's insulin supplement", if you will, and particular helpful for non-insulin-dependent type-II-diabetics.
  3. Effects on skeletal muscle are neglected - Anything that can potentially help build and maintain muscle tissue (and we all know whey can do that) will help with glycemia, obesity and lipid metabolism, because the increase or (esp. in the elderly) maintenance of skeletal muscle mass ("Metabolic Currency" - Carl Lanore) will allow for greater intra-muscular glucose stores and fatty acid oxidation (assuming you are still insulin sensitive, cf. 1)
  4. The "satiety hormones" are overlooked - Similar to the muscle building effects, the increase in GLP-1, a hormone which is by no means just responsible for inducing satiety (read all about GLP-1 in my previous post "Eat More, Burn More and Lose Fat Like on Crack With GLP-1") have been hitherto largely ignored. And that despite the fact that increases in GLP-1 could be among the main reasons that whey and other EAA-rich protein sources have repeatedly been shown to help weight- and, more importantly,  fat loss and increase metabolic health (Ranganath. 1996; Baggio. 2007; Akhavan. 2011; Gerspach . 2011). 
Image 2: Real foods are better protein choices for the last weeks of a contest prep (image directly from Adelfo Cerame's kitchen)
In other words, while some of the "beneficial effects" in obese and insulin resistant individuals could actually turn against lean, active individuals, the muscle-building and "satiety hormone" induced metabolic effects make up for the potential fat storage in scenarios of energy overconsumption (remember: there is a certain margin of carloric surplus, where the laws of thermodynamics do apply, cf. "A Tale of Macro- and Micronutrient Modifications")

Whey is probably not your best choice for the final weeks of a contest prep, though

Still, if you are in the final phase of prepping for a contest and want that "paper-thin" skin conditioning, like our common friend Adelfo Cerame does, real-food protein sources like chicken, fish, lean meat etc. should be your main sources and protein shakes, an exclusive post-workout thing (in the last days, maybe not even that).

  1. Akhavan T, Luhovyy BL, Anderson GH. Effect of drinking compared with eating sugars or whey protein on short-term appetite and food intake. Int J Obes (Lond). 2011 Apr;35(4):562-9. Epub 2010 Aug 24.
  2. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007 May;132(6):2131-57.
  3. Claessens M, Calame W, Siemensma AD, van Baak MA, Saris WH. The effect of different protein hydrolysate/carbohydrate mixtures on postprandial glucagon and insulin responses in healthy subjects. Eur J Clin Nutr. 2009 Jan;63(1):48-56. Epub 2007 Sep 12
  4. Gerspach AC, Steinert RE, Sch√∂nenberger L, Graber-Maier A, Beglinger C. The role of the gut sweet taste receptor in regulating GLP-1, PYY, and CCK release in humans. Am J Physiol Endocrinol Metab. 2011 Aug;301(2):E317-25. 
  5. Lavigne C, Tremblay F, Asselin G, Jacques H, Marette A. 2001. Prevention of skeletal muscle insulin resistance by dietary cod protein in high fat-fed rats. Am. J. Physiol. Endocrinol. Metab. 281:E62–71
  6. Morifuji M, Ishizaka M, Baba S, Fukuda K, Matsumoto H, Koga J, Kanegae M, Higuchi M. Comparison of different sources and degrees of hydrolysis of dietary protein: effect on plasma amino acids, dipeptides, and insulin responses in human subjects. J Agric Food Chem. 2010 Aug 11;58(15):8788-97.
  7. Ranganath LR, Beety JM, Morgan LM, Wright JW, Howland R, Marks V. Attenuated GLP-1 secretion in obesity: cause or consequence? Gut. 1996 Jun;38(6):916-9. 
  8. Salehi A, Gunnerud U, Muhammed SJ, Ostman E, Holst JJ, Björck I, Rorsman P. The insulinogenic effect of whey protein is partially mediated by a direct effect of amino acids and GIP on beta-cells. Nutr Metab (Lond). 2012 May 30;9(1):48.


  1. Whey spikes insulin and insulin is not the devil? Say that in a locarber's forum and get crucified! Never mind that it's true.

    I probably missed the post that would have explained this (or didn't understand it), but why not whey during final contest prep? (Not that I'll ever be in that situation -- I just need to lose 5 kg of fat).

    Interesting how much attention incretins have been getting, isn't it?

    1. the insulin spike, the glucagon (to compensate for the lack of glucose due to the pre-contest diet), the ups and downs in blood sugar all contribute to water retention, therefore you will stay leaner on "slower" less-insolinogenic protein sources, and you won't build muscle in the last weeks pre-contest anyway ;-)

      wrt to the incretins, I agree... I would like dozens of studies (like eating slow vs. fast for example) be redone to see what can influence those gut hormones

  2. It's not a big deal, but the article should say "beta cells in the Islets of Langerhans"

    whereas Langerhans cells are dendritic cells doing immune surveillance in the skin, etc

    1. you mean in the headline? I had "den langen Hans" in it, but that made it too long *rofl*

  3. If I knew German I might know what you're talking about :) Except that 'langen' means 'long', ja?

    But I was referring to "...Langerhans cellls (the cells of the pnacreas that are responsible for insulin mediated glucose control)"

    Hey, speaking of language, can you one day work in the word "cumber"?
    There's a fellow named Conan that uses it in this deleted scene:

    "almost twenty years of pitiless cumber". Ever seen that scene?

    1. sounds cumbersomely handsome ;-)

    2. langerhans, btw. is somewhat like "longjack" only that the latter is intentionally somewhat obscene *lol*

  4. I hate protein powder. I hate it with a passion normally reserved for racists and loaning money to family but I also hate meat and my nutritionist told me that I needed to start consuming one or the other. I have a strong dislike for chocolate and peanut butter unless it's in the form of a Reese's (which is oddly enough not laced with protein) and can't stand Strawberries so I bought this unflavored. When made with just water, it's tasteless. Completely, utterly, blessedly tasteless. Read More

    1. What is the point of this post? Mix your whey with sugar and cinnamon or whatever to add flavor.

    2. Prolly attempt to push traffic on his 'blog'.

  5. You mention, "slower" less-insolinogenic protein sources.

    Just to be sure I understand the article, is it impossible to make whey isolate "slower" (e.g., by eating a lot of nuts first) because it's not an issue of how fast the whey is absorbed, but rather the insolinogenic properties are due to some molecular-level feature of the whey?


    1. I guess it is also a function of how fast it is absorbed, but nuts first wont help. Unless you puree 500g and slurp those. The addition of fat in to carbs increases the insulin spike, by the way... so bad MYTH wrt to "add fats to avoid insulin" - for protein there is no effect ; read up on this, here =>