True or False? Adding Fat to A Carby Meal Lowers Insulin Response. Muscle Hypertrophy Impairs Oxygen Diffusion. Reducing Carb Intake Improve Muscular Insulin Sensitivity

Will the additional butter on top of the potatoes reduce the insulin response? You can find the answer to this and the other questions in today's episode of "True or False?"

If you are a regular here at the SuppVersity you should by now recognize the "True or False" part of the headline of today's SuppVersity article. Therefore it's probably unnecessary to say this explicitly, but this is a new series, where I could use a little help from your side. Well, ... I should say, I believe it would become even more fun, if you lend me a hand and send me short pieces of wisdom or idiocy like "Adding fat to a carby meal reduces the insulin response"  you deem worthy of being addressed in the True or False series. I cannot, or rather will not promise that I will address each and every of your suggestions, but if it interests me and can be tackled in a 2-3 paragraph text, your chances ain't bad to get your suggestions dealt with - if you got any ideas, just post them in the comment section of one of the previous installments (including today's, obviously).

Adding Fat to A Meal Will Ameliorate the Insulin Response

False. When you are browsing the Internet it is easy to get the impression that what is wrong or right is not determined by scientific evidence, but by the number of people who repeat it in their blogs, on their facebook walls and in their bulletin board contributions. The common "wisdom" that it would be a good idea to add some fat to a meal to reduce the insulin spike it will give you is one of those paradigms that remain intrinsically flawed no matter how often they are repeated.

Figure 1: Althoug the glucose AUC drops after the addition of fat (slowed absorption of glucose from the intestine), the amount of insulin (2ndary axis) that is needed to stash the glucose away is 8.5x higher (on a per unit base; cf. violet bar) and the absolute insulin response does not decrease at all in lean healthy men and women (Collier. 1983)

If you do take a look at what actually happens, when you add fat to a meal, it is yet not difficult to understand how that myth came about. Just like people don't understand that the GI of a certain carbohydrate source doesn't tell you much about it's effect on insulin, the fact that the addition of fat ameliorates the postprandial spike in glucose gets misinterpreted as "fatty meals are less insulinogenic than low fat meals". In fact, the addition of 50g of butter on top of the 50g of carbohydrates the 8 lean, weight stable men and women (N=4, each) consumed in form of potatoes, did not have any effect on the post-prandial insulin release at all.

GIP Or Not GIP - That is the Question: "Fat intake, in addition to ingestion of carbohydrate, stimulates GIP release. Therefore, during a mixed meal GIP might act to promote the storage of both triglyceride and glucose indirectly via the release of insulin." (Kieffer. 2003)

The amount of the fat storage peptide GIP (learn more), on the . Therefore, Collier and O'Dea are 100% right, when they state in the conclusion of their 1983 paper that...

"despite the apparent improvement in glucose tolerance when carbohydrate is ingested together with fat, the accompanying potentiation of insulin secretion could form the basis of long-term changes in insulin sensitivity which accompany alterations in dietary fat intake." (Collier. 1983)

You may want to remember that, whenever you feel inclined to add a ton of bacon on top of your sweet potatoes in the false believe that this would "mitigate" the effects of the carb-laden tubers the insulin response.

This obviously does not change the fact that having some fat in a meal does have the added benefit of increasing GLP-1 and PYY levels and thus contributing to a longer satiety effect (eg. Knut. 2008)

 Skeletal Muscle Hypertrophy Impairs Oxygen Diffusion

"Some HIIT For Life & Less LISS For More!" As the study at hand shows, this mantra is all the more important for the more muscular SuppVersity readers - that does not change that exercising longer to burn more fat won't work for anyone, muscular or not (learn why).

True! Contrary to the previous myth about the beneficial effects of adding fat to a high carb meal, which was not just totally messed up, but also pretty well-known the physical necessity that marked skeletal muscle hypertrophy will have a negative effect on he O2 diffusion of the "balooned up" musculature is something I would guess few of you have ever heard about before.

I have to admit that the 15-20% reduction in maximal oxygen consumption per kg of quadriceps mass a group of researchers from the University of Udine observed in 11 young athletes with marked skeletal muscle hypertrophy induced by long-term resistance training (body mass ~103kg), when they compared their them to 11 normal controls (body mass ~77kg) looks scary at first.

If you do yet also take into consideration that this decrease in oxygenation was accompanying improvements in ADP-stimulated mitochondrial respiration (+59%; takes place, when the ATP stores are used up) and a tighter coupling of oxidative phosphorylation, it becomes evident that the training induced enhancements in mitochondrial respiration seem to compensate for the hypertrophy-induced impaired peripheral O₂ diffusion.

"The net results are an enhanced whole body oxidative function at peak exercise, and unchanged efficiency and O₂ cost at submaximal exercise, despite a much greater body mass." (Salvadego. 2013)

In other words, despite "suboptimal" oxygenation of the musculature a bigger metabolic engine will still burn more fat... but only when it's working at peak intensity. It won't do so at submaximal intensities, where the O2 costs are "identical" (statistically). So, what does that tell us about the usefulness of training in the non-existent fat burning zone for advanced, heavily muscled trainees? Yep, it's even smaller than for the average sedentary housewife.

Low Carb High Fat Diets Lead to Acute Improvements in Muscular Insulin Sensitivity

False. Although the slowly abating low-carb craze does still make it appear as if "just eating less carbs" was the solution to everything, it is only logical that low carb dieting leads to changes in skeletal muscle insulin signaling, i.e. decreases in insulin-stimulated tyrosine phosphorylation of IRS-1 and PI3-kinase activity, which reduce, not increase the ability / willingness of the musculature to suck up glucose from the blood stream within no more than 5 days (cf. Pessin. 2000; Reusch. 2002).

Figure 2: Changes (before vs. after 5-day intervention) in fasting glycemia and lipidemia and glucose rate of appearance and disposal during euglycemic clamp conditions (Wang. 2013)

So even in the absence of significant effects on the body composition or signs of full-blown whole body  insulin resistance, the changes Cecilia C.L. Wang and colleagues observed in muscle samples that were taken from their insulin tolerant, but overweight subjects are identical to those you would observe in the early stages of diabetes, and do thus predate "changes in whole body insulin sensitivity" (Wang. 2013).

"But that ain't low carb!" Certainly a valid critism w/30% carbs and 20% protein in the diet it is practically impossible to reach ketosis, but - believe it or not - this is representative of the "low carb" diets you will usually see in the pertinent literature.

Wang et al. base their conclusion on the results of a recently conducted weight loss intervention that involved 18 obese individuals without diabetes who underwent euglycemic-hyperinsulinemic clamp and skeletal muscle biopsy after:

• 5 days of eucaloric diet (30% fat, 50% carbohydrate), and 

• 5 days of a 30% calorie-restricted diet, containing either...

• LF/HC: 20% fat, 60% carbs
• HF/LC: 50% fat, 30% carbs.

As mentioned in the introduction it's only logical and not necessary a bad thing that the skeletal muscle of the LF/HC group reacted with favorable changes in inulin receptor phosphorylation and lead to improvements in the IRS-1-associated PI3-kinase activity, which also figures in the exercise and nutrient induced increase in skeletal muscle protein synthesis (its among others the main target of IGF-1, of which keto dieters are known to have significantly reduced levels, anyway; cf. Fraser. 2000; Glass. 2003).

In other words, "No, 'just eat no carbs' is not the solution to everything", but will lead to certain metabolic adaptations which are not exactly conducive to returning to a normal carb diet afterwards. Plus, if you are a lean gymrat striving to to maximize your lean mass gains the full-blown hepatic growth hormone resistance and corresponding -50% drop in hepatic IGF-1 mRNA expression Bielohuby et al. observed in a rodent model of ketogenic dieting in 2011 probably won't come handy in the long run (on a side note: The "keto rodents", with their 92.8% fat diet also had a 5% reduction in lean mass and 46%, 56% and 223% higher relative amounts of visceral fat in the inguinal, epididymal and perirenal fat pads; cf. Bielohub. 2011)

Keep in mind this is a physiological form of insulin resistance

Learn how Adelfo lost his carbophobia and saw nothing but benefits from it (read more). That someone in the >30kg/m² BMI region with type II diabetes should keep a close eye on carb intake is a whole different story.

That being said, it is at least in part due to this mechanism that this type of diet works so well for highly insulin resistant individuals. It does not require the body to become insulin sensitive to work, but provides your body with a substrate that would - in and out of itself - require a certain degree of insulin resistance to make sure your muscle don't suck away the little glucose that's floating around and make you feel miserable and hypoglycemic. That you cannot observe those changes with a glucometer at home should be obvious. After all you are not eating carbs, are you?

Would the effect have been different with a true keto diet? The weight loss? Maybe. The transient insulin resistance? More pronounced, if anything. If you are already obese and freakin' insulin resistant to begin with, this does yet hardly matter. Low fat, high fat, keto - I don't care! The weight loss, the ensuing reduction in chronic inflammation and the new room to actually stash away superfluous energy alone will sooner or later also help you to reduce your insulin resistance.

Suggested read on physiological (=adaptation to diet / exercise) insulin resistance: "The Marathon Paradox - How Temporary Exercise-Induced Insulin Resistance Paves the Way for Fat Burning Machines" (complete article)


References:

• Berk ES, Kovera AJ, Boozer CN, Pi-Sunyer FX, Johnson JA, Albu JB. Adiponectin levels during low- and high-fat eucaloric diets in lean and obese women. Obes Res. 2005 Sep;13(9):1566-71.
• Bielohuby M, Sawitzky M, Stoehr BJ, Stock P, Menhofer D, Ebensing S, Bjerre M, Frystyk J, Binder G, Strasburger C, Wu Z, Christ B, Hoeflich A, Bidlingmaier M. Lack of dietary carbohydrates induces hepatic growth hormone (GH) resistance in rats. Endocrinology. 2011 May;152(5):1948-60.
• Collier G, O'Dea K. The effect of coingestion of fat on the glucose, insulin, and gastric inhibitory polypeptide responses to carbohydrate and protein. Am J Clin Nutr. 1983 Jun;37(6):941-4.
• Fraser DA, Thoen J, Bondhus S, Haugen M, Reseland JE, Djøseland O, Førre O, Kjeldsen-Kragh J. Reduction in serum leptin and IGF-1 but preserved T-lymphocyte numbers and activation after a ketogenic diet in rheumatoid arthritis patients. Clin Exp Rheumatol. 2000 Mar-Apr;18(2):209-14.
• Glass DJ. Molecular mechanisms modulating muscle mass. Trends Mol Med. 2003 Aug;9(8):344-50. Review.
• Kieffer TJ. GIP or not GIP? That is the question. Trends Pharmacol Sci. 2003 Mar;24(3):110-2.
• Knuth ND, Shrivastava CR, Horowitz JF. Reducing dietary fat from a meal increases the bioavailability of exogenous carbohydrate without altering plasma glucose concentration. J Appl Physiol. 2009 Jan;106(1):122-9. doi: 10.1152/japplphysiol.90404.2008. Epub 2008 Nov 13. 
• Pessin JE, Saltiel AR. Signaling pathways in insulin action:molecular targets of insulin resistance. J Clin Invest. 2000;106(2):165–9.
• Salvadego D, Domenis R, Lazzer S, Porcelli S, Rittweger J, Rizzo G, Mavelli I, Simunic B, Pisot R, Grassi B. Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training. J Appl Physiol. 2013 Mar 21.
• Reusch JE. Current concepts in insulin resistance, type 2 diabetes mellitus, and the metabolic syndrome. Am J Cardiol. 2002;90(5A):19G–26G.
• Wang CC, Adochio RL, Leitner JW, Abeyta IM, Draznin B, Cornier MA. Acute effects of different diet compositions on skeletal muscle insulin signalling in obese individuals during caloric restriction. Metabolism. 2013; 62:595–603