Eight Meals Instead of Three Keep Leptin & Insulin Stable and Shift the Nigh-Time Leptin Peak Towards the Early Morning - Impressive? Well, What is That Good For, Then?

All at once, in three or eight equal portions? That is the question... well, I guess these days no one would even dare saying that you should eat all the three "meals" in the middle column individually in order to make it to the 8 meals a day line, but in 2004, when this study was published things, were still a little different. For good reason?
It has become very quiet in the "eat as many meals as possible" camp in the last couple of years. In fact even the majority mainstream dietitians who have long been promoting 6 meals or more per day are now recommending three square meals and no more than "healthy" snacks in-between.

Against that background the recent study from the Leiden University Medical Center in the Netherlands appears to come right from the nutritional Middle Ages and that despite the fact that it was conducted "only" 9 years ago. I mean, the scientists did not compare three to two or one meal, deal with intermittent or alternate day fasting, but found it pretty natural to see beneficial effects in the hormonal profile of their five healthy obese female subjects (BMI 25–35 kg/m²; stable body weight), when they would feed them eight instead of three meals.

What the scientists were interested in were the insulin, leptin & cortisol responses

... of the ladies to the two dietary regimen. To this ends all subjects had to follow identical diets consisting of of a "normal quantity of macronutrients" (approximately 71 g of protein, 30% of calories as fat, and 55% of calories as carbohydrates) from common foods. The diet had an average coloric content of 2400-2500kcal per day and was consumed in either
  • three equally sized servings - breakfast at 08:15, lunch at 13:30 and dinner at 18:30, or
  • eight equally sized servings - eaten every 3 h (09:00, 12:00, ... 24:00, 03:00, 06:00) 
Since this is a cross-over study it is important to note that the diets of the first and of the second phase were completely equal in composition and content. What could be a potential problem, though, is the fact that the subjects did not stay at the lab, but ate their food at home. If you take a peak at the results, it does yet appear as if no one has been cheating badly. Otherwise, the pattern would have had unexpected troughs and spikes.
Figure 1: 24h profile of leptin (left) and insulin (right) during the 3x and 8x feeding condition (Fogteloo. 2004)
Apropos troughs and spikes, if you take a look at the results the differences look pretty profound. A cluster analysis did yet reveal that neither the insulin nor the leptin levels showed significant differences in terms the area under the curve, the mean 24h concentration, the burst frequency and interval, etc.

What did however differ significantly were the size of the amplitudes and the time at which the acrophase (maximally elevation) for the leptin levels occurred. With a 50% lower amplitude the leptin levels on the eight-meal condition were much more stable and the acrophase was shifted from ~1 o'clock AM to ~3:40 AM. In conjunction with the lower insulin levels in the waking hours could indicate a higher propensity to oxidize fat as the main fuel source, but as mentioned in a couple of previous articles, this does not necessarily have to be beneficial.

Fine, so we can postpone the leptin peak, but what's that good for?

While it is certainly interesting that we can influence the peak time and amplitude of the leptin levels by the way we eat, I highly doubt that there are physiological benefits associated with the decrease in irregularity, the 160min time-shift of the 24h peak and the overall lower leptin amplitude in the 8 feedings per day trial.

Figure 2: Aside from the missing cortisol "spike"at 10 PM the cortisol profiles during the two interventions look virtually and are statistically identical. So if there were any advantages to one of the feeding strategies it is probably not related to cortisol.
I know that one of the mechanisms by which the researchers in the "Carbs Past 6PM Studies" tried to explain the beneficial effects of their "eat your carbs before bed" approach were increased leptin levels during the day, this shift was much more pronounced in response to the macronutrient-timing approach vs. the food frequency approach in the study at hand (go back and look at figure 1).

Similarly, missing cortisol "mini spike" at 10pm (see figure 2) could be a disadvantage, when you think about the recently discovered relation between the presence of a natural up and down in cortisol and metabolic health (learn why). On the other hand it is a statistically non-significant difference in otherwise identical cortisol profile - a difference that appears to be way too small to actually make a difference.

Bottom line: Talking about differences, in the end, it would seem that it does not really make a difference in terms of your cortisol, insulin and leptin levels whether you eat three or eight meals. If you are insulin resistant you may argue that you could benefit from the lower absence of insulin spikes with the eight meal strategy, but in view of the fact that it is a pain in the ass to carry food around all the time and considering the fact that these mini-meals won't be satisfying for the majority of individuals, the study at hand does not provide any reasonable argument to consume eight instead of just three meals a day.

References: 
  • Fogteloo AJ, Pijl H, Roelfsema F, Frölich M, Meinders AE. Impact of meal timing and frequency on the twenty-four-hour leptin rhythm. Horm Res. 2004;62(2):71-8.
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