July 1, 2015

Glucose Metabolism, Satiety, and the Paleo Diet

Study suggests some benefits of Paleo diet but raises more questions than it answers
This randomized cross-over trial of 24 healthy men suggests possible benefits of the Paleo diet, but it raises more questions than it answers.


Bligh HF, Godsland IF, Frost G, et al. Plant-rich mixed meals based on Palaeolithic diet principles have a dramatic impact on incretin, peptide YY and satiety response, but show little effect on glucose and insulin homeostasis: an acute-effects randomized study. Br J Nutr. 2015;113(4):574-584.

Study Design

Randomized, cross-over trial, with investigator and outcome assessor blinded


Twenty-four apparently healthy males aged 18-60 years: Participants were mostly normal weight (calculated body mass index between 18 kg/m2and 27 kg/m2).


Meals were prepared fresh or frozen and quantities kept strictly controlled. There were 3 diets assessed: Paleolithic diet 1 (PAL1), Paleolithic diet 2 (PAL2), and reference diet (REF). PAL1 and PAL2 were devoid of dairy and cereals, while REF was devoid of dairy and used polished white rice as the “cereal” component. 
PAL2 and REF were matched for macronutrient content with 60% carbohydrate, 25% fat, and 15% protein diets. PAL1 was higher in protein (due to added white fish) with a ratio of 43% carbohydrate, 23% fat, and 29% protein.
The only vegetable in the REF group was carrot, and the only fruit was mango. PAL1 and PAL2 included strawberries, apples, yellow peppers, onions, eggplant, mushrooms, and raisins. They also included cinnamon, capers, and flaxseed oil. Only PAL2 diet included nuts, as almonds. All diets used farmed salmon as their base animal protein (13 g/meal).
Total calories per meal were 1,602 (REF), 2,328 (PAL1), and 1,606 (PAL2). Total fiber content per meal was 3 g (REF), 12 g (PAL), and 10 g (PAL2).

Study Parameters Assessed

Assessed were the acute effects on blood glucose control, gut hormone responses, and appetite regulation of 2 Paleolithic-type meals (PAL 1 and PAL 2) and a reference meal based on World Health Organization guidelines (REF). Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) concentrations were measured over a period of 180 minutes. PAL2 and REF were matched for energy, protein, fat, and carbohydrates; PAL1 contained more protein and energy. Satiety was also assessed using electronic visual analogue scale (EVAS) scores. 

Primary Outcome Measures

Plasma glucose, insulin, GLP-1, GIP, PYY, and satiety score

Key Findings

Appetite-related gut hormones, GLP-1, and PYY concentrations were significantly increased across 180 min for both PAL1 and PAL2 (P=0.011 and P=0.003) compared with the REF. Increased satiety scores via EVAS were seen with both PAL1 and PAL2 compared to the REF. GIP concentration was significantly suppressed with PAL1 and PAL2 compared to the REF, suggesting decreased need for insulin secretion with those 2 diets. Changes over 120 minutes for glucose and insulin did not differ between the meals.

Practice Implications

The popularity of the “Paleo diet” is in full swing as book after book and blog after blog continue to tout its seemingly endless potential benefits and purported perfect fit to the human genome.1 Unfortunately, a significant portion of support for this dietary approach has been based on anecdote, personal testimony, logical reasoning, and assumption. There have in fact been few high-quality studies investigating its theories to the extent necessary to prove that this approach results in positive effects unique only to it or that it is safe, especially in the long term.
In addition, as time has passed, more than 1 version of the Paleo diet seems to have surfaced. Some versions focus on the animal foods in a lower-carbohydrate, higher-protein, higher-fat version of Paleo, while others support use of a more plant-based version. Some adherents to the Paleo diet follow various additional rules they personally consider to be Paleo. In actuality, it is impossible to say which approach is more Paleo, as the entire notion of what truly constitutes a Paleo diet is still in question.2,3
Even if there were positive effects determined to be unique to the Paleo diet such effects may be offset by the potential for negative effects that can be seen only when additional physiological measures are examined.  
At first glance, in spite of its relatively small number of participants, this current study appears to help fill in the gap of missing higher-quality studies, this time in regards to effects of the diet on certain aspects of blood sugar metabolism. This study even goes so far as to account for and examine effects from 2 separate versions of the Paleo diet: 1 with more energy from carbohydrates (PAL2) and the other with more energy from protein and fat sources (PAL1). 
As the authors note, the analysis revealed some positive effects from both versions of the interventional diets used, specifically in regards to satiety and incretin production. GLP-1 and PYY, whose secretion appeared to be enhanced by these diets, both work to improve blood sugar levels through different means. GIP secretion, which stimulates insulin output, was tempered by both versions of the diet. 
Such effects can certainly be taken as positive, and if we were to stop there, a superior effect relative to what is meant to be representative of a more standard version of a healthy diet would be apparent. However, a closer look at the study’s conclusions, as well as the details of the study design itself, leaves us with more questions than answers about any potential unique effects attainable from the Paleo diet. 
Therefore, when evaluating this study, we should be asking ourselves a primary question: Does the Paleo diet provide a unique effect unattainable from other, dissimilar, and/or less restrictive diets? Considering this question then begets more questions:
  1. Is there a certain characteristic of the diets used that confers the benefits seen but is not actually unique to the Paleo diet? In other words, could a simple lack of one or more parameters of food quality account for the relatively poorer performance of the reference diet in this study?
  2. Are there any potential negative effects of the Paleo diet that would not necessarily be seen when evaluating acute effects on blood sugar parameters only?
To help answer question 1 above, we need to look closely at the differences between the REF and Paleo diets in terms of macronutrients. While some differences are present in terms of carbohydrate-to-fat-to-protein ratios, the key difference we should note involves fiber content. The REF meal contained a paltry 3 g dietary fiber, while PAL1 and PAL2 contained 12 g and 10 g, respectively. Multiplying each by 3 to attain an estimated daily intake would lead to 9 g total for REF vs 36 g and 30 g for PAL1 and PAL2. Even compared to the fiber intake of the average American,4 9 g is seriously low, while 30+ g at least satisfies current recommendations for daily intake.5 In other words, with the primary carbohydrate source being polished white rice, the REF meal contained almost no fiber at all.
Our answer to question number 1 can thus be attained when we investigate whether simply adding more whole food fiber to our diet could lead to the same sort of changes detected in this study with consumption of either Paleo diet. The answer is, “Yes, it can.”6-9 Therefore, it can be argued that the key positive effects seen with the Paleo diets used in the study actually have little or nothing to do with their being Paleo. Instead, these diets may have impact simply because they include more fiber than the REF diet did.
The answer to question 2 above is much more complex and difficult to find, and this article is not an appropriate medium through which to fully explore it. Nonetheless, it is important to highlight a few points that the reader may more fully explore. The primary point to consider is, if either or both Paleo diets are consumed long term, whether they could lead to problems not hinted at when simply exploring acute effects on blood sugar metabolism alone. 
Specifically, especially in regards to PAL1 (again, a lower-carbohydrate, higher-fat version) but also PAL2 (still relatively high in saturated fat and low in certain types of dietary fiber and resistant starch), it is important to consider potential negative effects some of the key dietary components could have on inflammation,10,11 endotoxemia,11,12 cholesterol/vascular health,13-15 certain types of tumor growth,16,17 and bowel flora18-20 and the impact such effects could have long term. 
It appears plausible that, even if there were positive effects determined to be unique to the Paleo diet (which this study does not actually prove there are), such effects, especially in terms of PAL1, may be offset by the potential for negative effects that can be seen only when additional physiological measures are examined. Therefore, before reaching conclusions suggestive of unique and/or positive effects from this popular diet-style, further study should be undertaken to investigate these additional parameters.

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