Appetite regulation part 3: What about food?

Updated: Jan 3

Mechanisms? √

Gut hormones


Now it's time to explore a more holistic approach to managing appetite, in the form of food. As discussed previously, we know elevating anorexigenic peptides through exogenous peptide infusion suppresses appetite, but can we manipulate our gut peptides with diet?


Why measuring appetite response to diet is SO difficult

Before we get started I'd like to quickly caveat this piece by mentioning how difficult it is to accurately measure appetite. Foods, nutrients and diets produce different physiological signals which can be measured and provide us with an objective marker of a physiological responses to food. However, food also elicits different behavioural and hedonic responses that are much harder to measure, and ultimately make it difficult to gain an accurate reflection of the true satiating properties of food.


For example, just because the body secretes appetite suppressing hormones to reduce food intake does not always equate to a reduced food intake. The hedonic response of food can lead to a cognitive drive to 'pleasure' ourselves by consuming more of a particular food, leading to overconsumption despite feeling full. In addition to this, the sight and smell of food, and the anticipatory expectations of how satiating a food can influence feelings of fullnes.



  • John Blundell, Rogerss, and Hill (1987) proposed that satiety was determined by more than just the gastrointestinal response to food. Their satiety cascade proposes that cognitive and sensory signals produced by sight and smell of food influence the volume of food consumed during a meal (satiation), but also post-prandial food intake too.


To obtain an accurate measurement of appetite in a clinical setting, the behavioural and physiological responses to food should be accessed. To measure the full appetite response of a food, the following measurements can be recorded:

  • Energy intake

  • Influence on gut hormones

  • Rate of gastric emptying

  • The hedonic response of food

  • Subjective markers of appetite (hunger scales)

Unfortunately, the volume of data within this field is scarce, and more studies are needed to further our understanding. At the present time, preload studies dominate comparative dietary appetite analysis. A preload study is when participants consume a meal, food or nutrient and then researchers record post-prandial energy intake and hunger scores. Since our improved understanding of the signals that regulate appetite, recent evidence has identified mechanisms of how certain nutrients influence these signals, but it's always important to practically test our theoretical understanding. So, which foods or diets have the greatest satiating effect? Let's waste no more time and get started, shall we?


What about food? 

Food is, of course, the biggest influential factor in appetite regulation. Each food contains calories based on the macronutrient profile of a food. The three macronutrients are:

  • Fat (9kcal/gram)

  • Protein (4kcal/gram)

  • Carbohydrates (4kcal/gram)

There's lots of interest in how nutrients and food influence appetite, as managing or tackling hunger is one of the most important factors for any diet to work. If a diet can increase fullness throughout the day then this will reduce overeating and be particularly helpful for those looking to lose weight. It's important to remember that fat, carbohydrates and proteins are umbrella terms for numerous different nutrients which fit in that category. Some fats, protein and carbs will induce different appetite responses than others.


Fibre

Dietary fibre is commonly referred to as an indigestible form of carbohydrates as humans lack the appropriate enzymes to deconstruct the bulk of dietary fibres, therefore, allowing them to pass the upper GI tract unaffected. One could argue fibre is indeed digested once reaching the colon, where the gut microbiota ferments fibre into short-chain fatty acids (SCFA).


SCFA are organic fatty acids that consist of 1-6 carbon atoms. The most abundant are acetate (2 carbons), propionate (3 carbons) and butyrate (4 carbons), 95% of SCFA produced in the cecum or large intestine are rapidly absorbed by cells lining the colon, with 5% secreted in faeces (1).


These cells in the colon (enteroendocrine cells) have numerous SCFA receptors, such as Free Fatty Acid Receptor 2 (FFAR2) which is a G-Protein-Coupled Receptor (2,3). Of all the SCFA's, it seems propionate has the highest affinity for FFAR2 (identifying a potential target). Propionate, unlike other SCFA's such as acetate, is the end product of bacterial metabolism and therefore does not undergo further conversion to other SCFA's, explaining its high affinity (4).


Increasing colon propionate concentrations secretes both PYY and GLP-1, in addition to reducing energy intake and weight gain in obese subjects (5). Although epidemiological data has associated dietary fibre with increased fullness (6), there have surprisingly been few studies that have explored this association in a more controlled setting. Certainly, added fibre reduces food intake compared to more refined carbs (wholemeal bread vs white bread (7), barley vs white wheat bread (8), and preload studies have shown a high fibre meal to be more filling and reduce energy intake compared to both a high carbohydrate no fibre meal and a high-fat meal (9).


When participants were given either 30g of inulin fibre or 30g of cellulose fibre, weight loss was achieved and maintained throughout an 18-week duration under both interventions. PYY was significantly higher for the cellulose group, which was surprising considering it is one of the less-fermentable forms of dietary fibre (10).


  • Fibre shields intracellular nutrients from digestive enzymes. High fibre foods are the main substrate for microbial fermentation, as they are less permeable and therefore reach the distal gut and ferment into short chained fatty acids, signalling an appetite response.


A recent study performed in a highly controlled setting where participants stayed in an overnight clinic throughout the study duration demonstrated a high fibre plant-based diet resulted in reduced energy intake compared to a high-fat low carb diet (11). Although the gut peptide response was not measured, there was no difference in participants hunger scores throughout the study duration. This could suggest the increased energy intake under the high-fat diet was down to an increased hedonic response from fat intake. However, it's also worth noting that subjective hunger rating questionnaires being so ambiguous do have their limitations. Based on previous literature, it's highly likely fibre contributed to the reduced energy intake for the plant-based diet too. A meta-analysis comparing 12 randomised control trials found added soluble fibre reduced body weight compared to a placebo treatment, again, likely down to the satiating properties of the fibre (12).


Fibre also slows down the rate of gastric emptying (13), therefore the prolonged satiating effect could also be down to longer exposure and fermentation of SCFA's, resulting in a longer secretion of anorexigenic peptides.


There is a well-established link between SCFA and gut peptides, and as dietary fibre is the main substrate for microbial fermentation it can be assumed that fibre does hold unique appetite regulatory properties. Exploring the relationship between fibre, SCFA and appetite peptides is a relatively novel area of research. It does seem dietary fibre, based on preloading RCT's, supplementation trials and dietary comparative studies, can suppress appetite and reduce energy intake.


Protien 

Protein has long held its position at the top of the appetite suppressing hierarchy. It's actually quite difficult to argue with this. Preload studies have consistently shown a protein meal follows a reduction in energy intake and subjective ratings of appetite, compared to a high fat, and high carbohydrate meal with calories matched across all meals (14).


The mechanisms of how protein influences appetite is thought to be through targetting the anorexigenic peptides discussed in part 1. Another contributing factor, similar to fibre, could well be down to the delayed rate of gastric emptying following protein intake. There are enteroendocrine cells with large amounts of G-Protein Coupled Receptors involved in regulating satiety throughout the GI tract. The longer digestion of protein could well correlate to longer exposure and secretion of anorexigenic peptides throughout the GI tract.


There was an interesting study which demonstrated both GLP-1 and PYY were elevated up to 120 minutes after a high protein meal, significantly longer compared to both a high carbohydrate and high-fat meal (15). Indeed, anorexigenic peptides like PYY are elevated hours high protein intake (16), and this provides evidence to suggest there's much truth in the hypothesis that digestion duration equates to longer appetite suppression. The correlation between the rate of gastric emptying and peptide secretion warrants further research.



  • Post prandial PYY response following high protein/high fat/high carbohydrate meal (8:00). PYY is significantly elevated for a longer duration compared to both high fat and high carbohydrate meal.

On a side note, it's worth keeping in mind that there are different types of proteins which have different appetite responses. For example, casein and pea protein which seems to be digested more slowly compared to other proteins cause a greater appetite suppression compared to whey (17).


Fat

The fact that protein induces a greater reduction in appetite compared to a refined carbohydrate like sugar, despite containing the same caloric content highlights how not all calories will produce the same influence on satiety.


Fat is the most energy-dense nutrient and has traditionally been seen as holding unique satiating properties. However, more recent evidence highlights the contrary, and when calories are matched across foods, high-fat foods/diets have consistently shown to increase post-prandial food intake compared to both high protein and fibre. Although there are limitations in preloading studies, well controlled and longer term studies help build on this data (11).


  • Under an ad-libitum high fat diet participants consumed signfiicantly more energy compared to a high fibre plant-based diet.

That said, fat is more satiating compared to refined carbohydrates, as across feeding studies fat produces significantly greater appetite signals than carbohydrates. Although, it's worth noting that the control food/beverage is normally either glucose or maltodextrin, two refined carbohydrates. Adding fibre, as found in most complex carbohydrates would certainly increase the satiating properties.


Fat is digested more slowly in comparison to refined carbohydrates, which could help explain why it does produce a greater satiety response. Although there's limited research exploring the gut peptide response following a high-fat meal, a study comparing a high-protein, high-fat, and high-carbohydrate beverage showed a greater secretion in anorexigenic peptides for both high-protein and high-fat compared to the carbohydrate (no fibre) beverage (18).


A recent study demonstrated obese individuals significantly reduced energy intake under a low-carbohydrate diet. However, the control diet was participants 'normal' diet, which was already 44% fat and contained a large amount of ultra-processed foods, making these findings rather irrelevant in the context of appetite, but certainly highlighting the benefits of improving diet on health and weight-loss (19).


Ketones, produced during prolonged carbohydrate restriction have been shown to suppress appetite, which is why a high-fat ketogenic diet has satiating properties compared to a control diet (20). However, context is so important here. Again, does a ketogenic diet suppress appetite more so than a high protein and/or high fibre diet? An area that needs further research...again.


In summary...

It's difficult to confidentally establish a food satiety heirarchy. The current weight of evidence highlights the satiating properties of fibre, protein and fat over simple carbohydrates. Both protein and fibre seem to be more satiating compared to fat but furhter research is warranted to understand the exact mechanisms. Potential explanations could be that protein and fibre produce a greater anorexigienic response, as well as fat eliciting a greater hednoic response.


Ultimately, there will be other important factors of food composition away from the macronutrient profile, such as water and air content, and chewing rate too (21, 22,23). In addition to this, it's also important to take into consideration the food matrix and how other compounds not mentioned in this article influence metabolism.



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