Protein Study Uncovers Role of PYY and, Gasp! - Bias!

Quite a buzz was created by the publication of a study in the September issue of Cell Metabolism, Critical role for peptide YY in protein-mediated satiation and body-weight regulation.

From the summary section of the paper:

Dietary protein enhances satiety and promotes weight loss, but the mechanisms by which appetite is affected remain unclear. We investigated the role of gut hormones, key regulators of ingestive behavior, in mediating the satiating effects of different macronutrients. In normal-weight and obese human subjects, high-protein intake induced the greatest release of the anorectic hormone peptide YY (PYY) and the most pronounced satiety. Long-term augmentation of dietary protein in mice increased plasma PYY levels, decreased food intake, and reduced adiposity. To directly determine the role of PYY in mediating the satiating effects of protein, we generated Pyy null mice, which were selectively resistant to the satiating and weight-reducing effects of protein and developed marked obesity that was reversed by exogenous PYY treatment. Our findings suggest that modulating the release of endogenous satiety factors, such as PYY, through alteration of specific diet constituents could provide a rational therapy for obesity.

Cliff notes version:

A high protein diet led to spontaneous calorie reduction as PYY increased. The phenomenon was consistent with both the animal model using mice and in human studies used to validate the mice model. Over a longer term, the higher protein diet stimulated weight loss and enhanced PYY synthesis and secretion in mice.

To better understand the role of PYY, the researchers used mice where the PYY coding region was deleted and found that without PYY, the mice, even on a high protein diet, gained weight and experienced hyperphagia (eating an excessive amount of food beyond needs).

Basically the PYY-null mice were resistant to the satiating effects of dietary protein.

The media quickly picked the findings of the study up and ran attention grabbing headlines:

• Probable Mechanism Behind Atkins Diet Revealed
• 'Proof' behind high protein diets
• Atkins-style diets suppress slimmers' hunger, says study
• Eat more meat to cut obesity
• Stomach growling? Eat a burger, study finds

Of course that last one made me laugh considering the headline last month that claimed A Bite Of Burger Can Cause Heart Attack!

The above headlines are designed to capture your attention and it's only when you read the article that you find the good examples of disconnect between the study published and what's put out there for public consumption.

Case in point, in the Nature article High-protein diet reduces appetite: Eggs, meat and cheese trigger a protein that makes us eat less, we find the lead researcher, Dr. Rachel Batterham quoted within the following paragraph:

[S]he cautions, that doesn't mean the Atkins diet is a good idea: "No medical person is going to tell you to have all that saturated fat in your diet and no carbohydrates." In its early stages, the regime causes a condition called ketosis, in which the liver, deprived of glycogen from carbohydrates, switches to its starvation mode and begins to metabolize fatty compounds. "The problem is that it makes you feel terrible," Batterham says.

Followed by, [s]he now plans to organize a long-term study of the effects of a high-protein diet in humans, which might feature foods such as lean meat, soy, tofu and egg.

Compare this with the full-text paper - The ready availability of carbohydrate-rich grains and cereals has been a recent development in human nutrition with the onset of organized agriculture. Many of the physiological systems that regulate food intake were probably established and may function better under lower-carbohydrate and higher-protein dietary conditions. This might explain the effects of protein on satiation and PYY release and the marked phenotype caused by the deletion of the Pyy gene.

To her peers, she writes about how our metabolism and the systems that regulate food intake may function better under carbohydrate restriction; the the public she perpetuates the myth that the Atkins diet (or an Atkins type diet) provide "no carbohydrate" and is one long saturated-fat-fest. ::::big eye roll:::::

I highlight the disparity to show readers how what they read in the media isn't always in synch with the primary source - the full-text paper that is published.

But that's not all.

Interestingly there is subtle bias that emerges in the full-text of the paper, which helps explain the public statements made regarding dietary fat.

Within the discussion, the citations of support for the satiety effect of protein include:

There is some limited evidence from human studies that these acute effects on satiety translate into longer-term benefits. For example, a 6 day intervention study examining the effects of a normal-protein (15%) low-fat American Heart Association diet compared with high-protein (31%) low-fat diet found that ad libitum caloric intake was reduced by 25% with the increased protein content diet (Dumesnil et al., 2001). In a randomized 6 month trial comparing ad libitum high-protein (25%) low-fat diet with a normal-protein (12%) low-fat diet for 6 months, Skov et al. demonstrated improved weight loss and fat mass loss with enhanced-protein diet, an effect attributed to reduced food intake (Skov et al., 1999). Furthermore, increasing the protein content of the diet from 15% to 18% during weight maintenance after weight loss has been shown to halve the amount of weight regained (Westerterp-Plantenga et al., 2004). Protein-rich diets caused the greatest satiation in our acute human and rodents feeding studies and the greatest reduction in weight gain in our chronic rodent diet studies, consistent with these published studies on the beneficial effects of dietary protein.

What's missing from the above citations?

The data from studies where protein and fat were consumed ad libitum - specifically the studies investigating carbohydrate restricted diets where subjects were allowed to consume protein and fat without limitation.

This very subtle bias doesn't change the data, but it does help us understand how preconceived notions enter into interpretation of the findings and the recommendations for additional research studies.

In this instance, it seems, the lines of scientific thought and inquiry are open for further exploration, as long as the researchers start with the assumption dietary fat, especially saturated fat, is bad.

It's an assumption that the diet-heart theory is not only valid, but infallible, that leads to limited lines of research inquiry - it's based on "let's ignore the fact that protein rich animal foods, in their natural state, often are packed with saturated fats - along with monounsaturated and polyunsaturated fats. Let's not look at data from studies where subjects were allowed to eat these sources of protein, and thus also consumed saturated fat; even the findings with beneficial improvements are unimportant here because of the saturated fat in the diet of these subjects. In fact, let's just contradict ourselves and our citation of Loren Cordain, his work exploring hunter-gatherer diets, and let's go investigate soy!"

So while this research expands our understanding of the role PYY plays in satiety, we see the researchers already setting the stage to investigate further within the dogmatic paradigm that dietary saturated fat is bad...forget the context of the diet, just don't explore the possibility that saturated fat may be a player here too! Go look at soy for goodness sake - there is just no way saturated fat may be beneficial....enough said.