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Food Order & Glycemic Control

iStock-1321195601In a controlled trial published in Nutrients (Oct 2023), the effect of altering the order in which foods are eaten on glucose tolerance (GT), HbA1c, weight, and nutrient intake was evaluated in a group of 45 adults with overweight/obesity and prediabetes. Specifically, researchers at Weill Cornell Medicine provided standard nutritional counseling to the control group, centered around the USDA MyPlate guidance, while the experiment group received additional counseling to consume carbohydrates last (referred to as the FO group, for food order). The FO group was given instructions to help classify foods as primarily belonging to one of three groups, vegetables, protein, or carbohydrate, to consume the vegetable and protein groups first at each meal, and to keep a food log recording their success at doing so for each meal. Counseling took place at baseline, as well as weeks 4, 8, and 12 in this 16-week study.

The results were positive, but not terribly impressive. Both groups lost weight, but there were no significant differences in GT, HbA1c, and weight loss between groups, though the FO group increased their daily vegetable and protein consumption (and adherence was quite high). However, when the analysis was restricted to a smaller pre-pandemic (COVID-19) cohort (12 in each group), the FO group lost 5.9lbs vs. 1lb in the control group, suggesting that interruptions associated with the pandemic, such as converting in-person counseling interventions to telemedicine, may explain the lack of overall benefit. Additionally, this was a fairly short-term study with a small sample size, further limiting its impact.

Perhaps more importantly, there seems to be considerable evidence supporting this change in food order established in previous trials. For example, a small study published in 2015 in Diabetes Care conducted a cross-over trial among participants with diabetes taking metformin. They found significant reductions in post-meal glucose (73% lower incremental area under the curve) as well as postprandial insulin levels when eating carbohydrates last. It’s important to note this comparison is between the same individuals eating the same meals, just a change in the order in which the same foods were eaten. One possible mechanism is greater secretion of GLP-1 when protein/vegetables are consumed first.

A 2014 study published in the Journal of Clinical Biochemistry and Nutrition included data from Japanese study participants and found similar improvements in post-prandial glucose and insulin among 15 subjects with type 2 diabetes. This same paper also reported results from a 72-hour study using continuous blood glucose monitoring among 19 subjects with diabetes and 21 with normoglycemia, again in a randomized cross-over study design. A significant take-away from this study? Although the mean glucose levels were the same when comparing the two dietary approaches (vegetables before carbs, or carbs before vegetables), multiple parameters favored the vegetables before carbs approach, including both the mean and large amplitude of glycemic excursions (MAGE and LAGE, respectively). In a nutshell, there were much bigger spikes and drops in glucose levels when eating carbohydrates early in a meal versus eating them last. Eating carbohydrates last had a glucose-stabilizing effect – this is a very important point. Although the mean (average) glucose levels were similar between groups, the highs and lows were very different. This same paper, while light on methodology, also reported on the effect of providing instruction to participants to consume vegetables before carbohydrates to 196 participants with diabetes and compared results at year 1 and year 2.5 to a control group of 137 given no specific dietary advice. Improvements in glycemic control were observed at both points, including a HbA1c drop of approximately 1%, compared to no change in the control group.

A 2023 systematic review published in the Journal of the American Nutrition Association used data from 11 reports and concluded (with moderate certainty) that consuming carbohydrates last lowers blood glucose and insulin excursions. So why isn’t this simple and easily followed recommendation made more often? This may be a result both of small study sizes and paying attention to the wrong biomarkers. For example, a 2022 systematic review & meta-analysis published in BMJ Open Diabetes Research & Care found “no evidence for the potential efficacy” of this approach. Drilling down into the 8 studies included in this systematic review, only 3 assessed HbA1c, with a combined total of 95 participants in that experimental group.

Perhaps more important is the choice of relevant biomarkers. Figure 3 in the 2022 systematic review includes a 2019 study published in Diabetes, Obesity, and Metabolism (Skukla, 2019), which appears to show a non-significant increase in mean plasma glucose with this dietary intervention, casting this approach in an unfavorable light (at least in the review). However, reading the actual study found lower post-prandial glucose and insulin excursions/peaks when eating carbohydrates last, i.e., more stable glycemic control, a favorable outcome. As easily observed in Figure 1 of this trial, there are much bigger spikes AND dips in glucose and insulin when eating carbohydrates first. Yet because there are both spikes and dips, the average may be the same, and a systematic review that only reports the average misses this highly clinically relevant difference. While restricting carbohydrates certainly may have advantages, simply eating them after vegetables and protein appears to as well, and perhaps is more sustainable.

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