The timing of carbs in meals makes a diference!



The spirit of science is not merely faith in the power of reason; it is also a belief that our problems may be simpler than they appear to be.

– Colin Wilson, The Strength to Dream

This recent pilot study is an example of good science for two reasons – it suggests that a minor change in behaviour can be a shortcut to important health benefits, and it raises more questions than it answers.

Alpana P. Shukla, Radu G. Iliescu, Catherine E. Thomas, and Louis J. Aronne.
Diabetes Care 2015;38:e98–e99 | DOI: 10.2337/dc15-0429

The authors looked at the effect of food order, using a typical Western meal (628 kcal:
55 g protein, 68 g carbohydrate, and 16 g fat), incorporating vegetables, protein, and carbohydrate, on postprandial glucose and insulin excursions in overweight/obese adults with type 2 diabetes. There were only 11 subjects (5 male, 6 female), which is why it’s a pilot study; the numbers were small, so any effect, to be statistically significant, actually had to be clinically significant too. But these people could be exceptions, the effect of metformin may be necessary for the response, it might vary when different foods are eaten, the effect might not be seen with larger meals, or in free-living populations, and the long-term effect on fasting glucose and insulin wasn’t investigated; so it’s a “proof of concept” type of experiment that tells us, loud and clear, that further investigations are certainly warranted.

The study was a cross-over design, meaning that both meal orders were tested in all subjects, a week apart. The meals were made up of ciabatta bread and orange juice (the carbohydrate part) and a chicken salad with low fat vinaigrette, plus broccoli and butter (the vegetable and protein part) and these two parts were eaten, separated by 15 minutes, in 2 different orders. Insulin and glucose were measured just before the meal and at 30, 60, and 120 minutes after the start of the meal.

When the vegetable and protein part of the meal was consumed first, mean postmeal glucose levels were decreased by 28.6%, 36.7%, and 16.8% at 30, 60, and 120 min, respectively, and the incremental area under the curve (iAUC) was 73% lower. Postprandial insulin levels at 60 and 120 min and the insulin iAUC were also significantly lower when protein and vegetables were consumed first.

Meal Order

The authors commented that “the magnitude of the effect of food order on glucose levels is comparable to that observed with pharmacological agents that preferentially target postprandial glucose. Moreover, the reduced insulin excursions observed in this experimental setting suggest that this meal pattern may improve insulin sensitivity.”

How can this be? The same food was eaten, and 15 minutes is not a very long time; it’s a sedate meal, but not a long-drawn out one.

No mechanism is offered in the paper, but we would like to suggest one. After a meal, and especially in people with type 2 diabetes, glucose does not only appear from the food eaten. Glucose is released from glycogen (the liver’s carbohydrate stores) in the fasting state, and this appearance of glucose may continue or even increase after eating carbohydrate, likely because of the post-prandial spike in glucagon, which is released from cells in the gut, as we described in an earlier post. This rise in glucagon in people with type 2 diabetes following carbohydrate consumption has not always been seen experimentally, but it appears as a significant effect in most studies, especially when carbohydrate is fed in a meal; it can clearly be seen here, where the diet is 55% carbohydrate (designed according to AHA and USDA Dietary Guideline recommendations, and represented by the circles – the triangles represent the baseline American diet, which had almost identical effects).
Nuttal 2004 HiCHO glucagon
(from Effect of a High-Protein, Low-Carbohydrate Diet on Blood Glucose Control in People With Type 2 Diabetes. Mary C. Gannon and Frank Q. Nuttall. Diabetes 53:2375, 2004

(This study also says “We and others also have reported that even short-term starvation (hours) results in a dramatic decrease in the blood glucose concentration in people with type 2 diabetes. This seems to be due largely to a rapid, progressive decrease in the rate of glycogenolysis.” Even when you’re fasting, glycogen release slows down once insulin drops and you start burning more fat.)

We suggest that feeding the vegetable and protein part of the meal first blunts the glucagon response to the carbohydrate portion. There could be multiple reasons for this – a delayed appearance of glucose in the gut, or the pre-emptive ability of the insulin, somatostatin 28, and incretins released in response to the protein part of the meal to suppress glucagon release, resulting in lower insulin release overall, because there is both less glucose from glycogenolysis and less glucagon, both of which require extra insulin.
This is only one possible explanation – we’d like to hear others – and verifying or refuting it will take (among other things) accurate measurement of glucagon and other peptides at many time points over the immediate post-prandial period, which is not easy.

Why might eating carbohydrate trigger the release of glucose from glycogen in some circumstances?

Imagine our early human ancestors; they didn’t eat all the time, and sources of dense and easily digestible carbohydrates were rare in some environments. It’s likely that these hominids adapted to hoard glycogen, saving it for an emergency, like sprinting from Pachycrocuta, the giant prehistoric hyena that hunted Homo erectus. And this meant that glucose, which can be used to fuel growth, and to store fat, glucose which we take for granted today, was usually restricted. In this context it made sense if, as soon as an appreciable amount of glucose was detected in the gut, some extra glucose from the glycogen store was released into the blood as well; this extra could be used wisely, and replaced later – the analogy is dipping into your savings for something special when you know there’s going to be lots of money coming in, then being a lot tighter in between paydays.
This (if it’s true) would be the adaptive system, and work when appropriate; and type 2 diabetes, by definition, means that adaptive systems of blood glucose control have become dysregulated and are poorly controlled. It’s a model that does help to explain why fasting and low carb diets can help to bring post-prandial glucose under control, but it’s a highly conjectural one, a “just-so story”.

Takeaways –

  • post-meal release of glucose from glycogen can make an important contribution to post-prandial blood glucose spikes
  • post-meal glycogen release can be triggered by eating carbohydrate
  • very low carb diets and fasting cause the body to conserve glycogen
  •  in this study, eating the carbohydrate portion 15 minutes after the protein and vegetable portion in a high-carbohydrate meal resulted in significantly lower post-prandial glucose and insulin spikes

We note that the carbohydrate timing study of Shukla et al. was “supported by the Clinical and Translational Science Center at Weill Cornell Medical College (UL1 TR000457) and the Dr.Robert C. and Veronica Atkins Curriculum in Metabolic Disease at Weill Cornell Medical College Grant” and that Dr David Ludwig, who was not an author, is thanked for helping to formulate the study hypothesis.

6 Comments on “The timing of carbs in meals makes a diference!

  1. According to a veterinary book I once edited, food layers in the top part of the stomach in the order in which it’s eaten. Liquids run right through, which is one reason skim milk is an excellent way to bring up a low. If you eat mashed potatoes first, they’ll go into duodenum first and raise BG. If you eat meat first, it will go into duodenum first but won’t raise BG much. It will also hold back release of the potato you eat next and thus slow down its effect. So Table 1 is consistent with this.

    • Thanks Gretchen, that’s a great explanation. The study didn’t go beyond 2 hours, so we don;t know if there were long-term effects that decreased the differences between iAUC. The glucose and insulin in the carbs-last group, though low, is still climbing – would it have matched the carbs-first group overall? I doubt it, and I think the glucose spike was dodged, but we need a longer study to be sure.
      In the meal we have orange juice, which would have run right through, and chiabatta. So we are also putting “catalytic” fructose before most of the glucose in the carbs-last group, which might do something as well (e.g. lower BG because increased triglyceride synthesis by the time most of the glucose comes in)..

  2. Hi Grant, I realize this has little to do with your latest post but what do you make of this? Cheers Tony.
    After hundreds of tests in the lab and numerous feed trials on countless sheep, animal science researchers from the University of Tasmania and the CSIRO have come up with a winning formula of feed pellets infused with omega-3-rich oils, including rice bran oil, safflower oil and canola oil.

    • Hi Bruce,

      I think this recent study, which looked at the appearance of saturated fat in the blood and inflammatory markers after the consumption of various carbohydrate loads by people with pre-diabetes, is a good indication that slowing appearance of carbohydrate by manipulation of GI has benefits.
      However, GI of different foods varies by individual, and what is low GI for you maybe high GI for me; also, the fact that fructose and sugar are low GI complicates things if going by GI alone. Feeding a diet high in legume carbohydrate (60% CHO), which is low GI but also low carbohydrate density, improved blood sugar in people with diabetes compared to a lower carb diet with refined carbs (40% CHO), but a lower CHO version of the same diet wasn’t tested, and would reasonably be expected to give even better results. We favour food that is both lower GI, low in carbohydrate density (for solid foods, grams of carbohydrate per 100g on the nutrition data sheet), in the pattern of a diet that is very low in carbohydrate for the initial treatment of diabetes, because this is most likely to lower post-prandial and fasting blood glucose and, by decreasing appetite, begin the weight loss that will reverse the pathology. Also, if eating very low carb veges and fruits you can afford to eat more veges and fruits and thus get more micronutrition.
      But for people who do tolerate carbs, and have no health problems that can be resolved by limiting carbohydrate, eating the carbohydrate part of the diet as exclusively non-processed carbs seems to be one way to avoid developing a carb-related pathology. Just don’t think that a quinoa or lentil salad every now and then will protect you from the effects of eating refined carbs the rest of the time!

  3. Here’s another study about the same question. This one only looked at glucose levels, not insulin.

    Manipulating the sequence of food ingestion improves glycemic control in type 2 diabetic patients under free-living conditions.
    D Tricò, E Filice, S Trifirò and A Natali
    Nutrition & Diabetes (2016) 6, e226; doi:10.1038/nutd.2016.33

    Lipid and protein ingested before carbohydrate reduce postprandial hyperglycemia. We tested feasibility, safety and clinical efficacy of manipulating the sequence of nutrient ingestion in patients with type 2 diabetes (T2D). After a 4-week run-in, 17 T2D patients were randomized to either a control diet (CD) or to an experimental diet (ED) allowing the consumption of high-carbohydrate foods only after high-protein and high-fat foods at each main meal (lunch+dinner). Both diets were accurately followed and neutral on arterial blood pressure, plasma lipids and indices of hepatic and kidney function. After 8 weeks, in spite of a similar reduction of body weight (ED −1.9 95% confidence interval (−3.4/−0.4)kg, P<0.03; CD −2.0 (−3.6/−0.5)kg, P<0.02) and waist circumference (ED −2.9 (−4.3/−1.5)cm, P<0.002; CD −3.3 (−5.9/−0.7)cm, P<0.02), the ED only was associated with significant reductions of HbA1c (−0.3 (−0.50/−0.02)%, P<0.04), fasting plasma glucose (−1.0 (−1.8/−0.3)mmol l−1, P<0.01), postprandial glucose excursions (lunch −1.8 (−3.2/−0.4)mmol l−1, P<0.01; dinner: −1.0 (−1.9/−0.1)mmol l−1, P<0.04) and other indices of glucose variability (s.d.: −0.5 (−0.7/−0.2)mmol l−1, P<0.02; Coefficient of variation: −6.6 (−10.4/−2.7)%, P<0.02). When compared with the CD, the ED was associated with lower post-lunch glucose excursions (P<0.02) and lower glucose coefficients of variation (P<0.05). Manipulating the sequence of nutrient ingestion might reveal a rapid, feasible, economic and safe strategy for optimizing glucose control in T2D.

    It contains this telling sentence:
    If applied also to the breakfast (scarcely feasible for Italian habits), the overall effect of this dietary intervention on glucose control, namely on glycated hemoglobin, would have probably been greater.

    And this:
    the physiological combination of lipid and protein is likely to be more effective, by acting on multiple targets; indeed, the effect on glucose tolerance of protein alone, though persistent, was quantitatively small.

    Bacon and eggs, hold the toast, anyone?

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