High-Protein Diets: More Than a Tool for Athletes? Part 1

High-protein diets have come in and out of fashion over the years, taking a variety of forms. Perhaps the most notable of which is the Atkins diet; an eating pattern that is also high in fat and severely restricts carbohydrates. 

While typically thought of as such, a high-protein diet is not always low in carbohydrates. It can take the form of a high-carbohydrate approach with limited amounts of fat as well. This style of eating is commonly employed by most bodybuilders.

With an understanding that a high-protein diet can significantly vary in its percentage of carbohydrates and fat, we can move on to the crux of the matter. That is, what amount of protein qualifies a diet as “high-protein”? 

As it stands, there is no ubiquitous definition for what constitutes a “high-protein diet” and scientists frequently use different definitions.

A diet may be considered high-protein if it exceeds the RDA (0.8 g/kg/day), the average protein intake in Western countries (15-16% of total energy intake), or falls within the upper half of the acceptable macronutrient range (10-35% of total energy intake). 

As a consequence of this lack of consensus, a high-protein diet can simply refer to an eating pattern that emphasizes the consumption of protein-dense foods. 

For the purpose of this article, a high-protein diet will refer to any eating pattern where protein intake comprises 25-30% of total energy intake.

In the fitness space, it’s been traditionally recommended to consume one gram of protein per pound of body weight. This recommendation dates back to the Golden Age of Bodybuilding when Arnold Schwarzenegger was dominating the competitive arena.  

Although this dietary advice stems solely from in the trenches experience, current evidence suggests that consuming one gram of protein per pound of body weight is likely a good idea to maximize muscle hypertrophy. 

As a result of a growing and robust body of evidence, a high-protein diet has become widely accepted and implemented by fitness enthusiasts everywhere to enhance body composition and improve recovery from exercise.

In contrast, the general public remains skeptical, and this is largely due to pervasive and unsubstantiated claims regarding the safety of a high-protein diet.

To quickly address a couple of these claims (I’m looking at you Jillian Michaels), a high-protein diet does not negatively affect bone health. In fact, higher protein intake is positively and linearly associated with bone mineral density.

Also, while restricting protein intake is a good idea for individuals in the latter stages of chronic kidney disease, a high-protein diet does not adversely affect kidney function in healthy adults

In summary, the available research suggests a high-protein diet is completely safe in otherwise healthy individuals.

If high-protein intakes are objectively safe for widespread use, and some of the healthiest people within society are thriving on this diet, then it makes you wonder, could those of poorer health be missing out? Would certain populations experience improvements in their condition from adopting a high-protein diet? 

In this series of articles, I will be answering this question. In each installment, I will examine the research on the efficacy of a high-protein diet in specific populations. First up, we’ll take a look at type 2 diabetes (T2D).

Diabetes Etiology

T2D is characterized by impaired pancreatic β-cell function and insulin resistance

The pancreatic β-cells initially produce insulin, but the malfunctioning peripheral tissues (i.e. muscle and adipose tissue) are unable to respond to the insulin, leading to chronically elevated blood glucose levels. 

The persistently high levels of blood glucose provoke a continued and increased demand for insulin, resulting in a progressive decline in β-cell function and defective insulin secretion.

Effect of a High-Protein Diet on Cardiometabolic Risk Factors

Over the past decade, a few meta-analyses have been conducted to examine the effects of a high-protein diet on body weight and cardiometabolic risk factors in people with T2D.

In the interventions included in these articles, “high-protein” is generally characterized as an intake comprising 25-30% of total energy intake, while “low-protein” typically refers to an intake of 15-20% of total energy intake.

In 2013, Dong and colleagues found a high-protein diet did not affect fasting glucose and lipid profiles, but had potentially beneficial effects on weight loss, HbA1c, and blood pressure, although the changes were quite modest.

For weight loss, the difference between consuming a high and low-protein diet was roughly 1 kg. For HbA1c, there was an average reduction of 0.30%. For blood pressure, there was a decrease of 5.99 and 3.57 mmHg for systolic and diastolic, respectively.

Since these findings, an updated meta-analysis was published by Zhao et al. in 2018. Building on the above by including more recent trials, this group found no significant differences in weight loss between high-protein and low-protein diets.

Further, changes in fasting glucose, fasting insulin, and HbA1c were similar between diets. Similar outcomes were reported for total cholesterol, LDL-cholesterol, HDL-cholesterol, and blood pressure as well.

The main finding of interest was that a high-protein diet may increase the reduction of triglycerides, but this could more so be a consequence of restricting carbohydrates, rather than consuming a greater proportion of energy from protein. 

In aggregate, these results report that increasing dietary protein intake may modestly improve weight loss and some cardiometabolic risk factors in people with T2D. 

More importantly, they suggest that improvement in cardiometabolic risk factors are primarily a product of weight loss, rather than the macronutrient distribution of the diet, and while high-protein diets are feasible and safe for individuals with T2D, they don’t always provide superior long-term metabolic benefit over a standard protein intake in the context of energy restriction.

The significance of weight loss for managing T2D has become increasingly clear in recent years as a relationship between the magnitude of weight loss and the achievement of T2D remission has been observed. The most notable study in this area is the DiRECT trial. 

The DiRECT trial utilized a low-calorie total diet replacement (825-853 kcal/day) intervention for 3-5 months. This was followed by stepped food reintroduction and a transition to a period of weight maintenance. 

The results displayed that remission was closely related to the degree of weight loss at 12 months. Remission was achieved by 86% of participants with at least 15 kg of weight loss and by 73% of those with a weight loss of 10 kg or more. In contrast, remission was only achieved by 7% of individuals who maintained a weight loss of 0-5 kg.

As evidenced by the above, total weight loss is paramount for ameliorating T2D. Even so, that does not mean there aren’t any benefits to manipulating the macronutrient distribution of the diet.  

In particular, increasing dietary protein intake may enhance the prevention and management of T2D by improving the effectiveness of weight loss and glycemic control. 

More Protein for More Effective Weight Loss

The consumption of protein has stronger satiety effects than carbohydrates or fats. Dietary protein has been shown to have a notable impact on appetite-regulating hormones, such as ghrelin, peptide YY, cholecystokinin, and glucagon-like peptide 1 (GLP-1).

Appetite (the desire or motivation to eat food) can be estimated by questioning five feelings; hunger, fullness, satiety, desire to eat, and prospective food consumption. Suppression of appetite in all categories has been documented in the hours following sufficient protein consumption. 

Correspondingly, high-protein ad libitum diets (25-30% of total daily energy intake) have been shown to lead to unintentional weight loss caused by reductions in daily energy intake, which may have occurred as a result of increased satiety.

In consideration of the tremendous importance of weight loss for T2D management, increasing protein intake may be a beneficial strategy to promote adherence to an energy deficit via improving appetite control.

Outside of suppressing appetite, a high-protein diet also leads to greater preservation of skeletal muscle mass while in an energy deficit, which has important implications for individuals with T2D. 

Skeletal muscle is vitally important for glucose homeostasis and metabolism. It is responsible for over 80% of glucose uptake from an oral glucose load.

Muscle mass tends to scale with insulin sensitivity and an inverse relationship between relative skeletal muscle mass and insulin resistance has been reported. Increases in skeletal muscle above even average levels have been associated with additional protection against insulin resistance. 

In this specific study, a 3% increment in muscle mass as a fraction of body weight was associated with a 3.4% and 3.7% relative reduction in HOMA-IR and prediabetes prevalence, respectively. In nondiabetics, the effects rose to a 4.4% and 7.5% relative reduction in HOMA-IR and prediabetes risk.

Concerning the critical role of muscle in glucose disposal and homeostasis, a weight loss intervention that significantly reduces both fat and muscle mass may be less effective in the prevention and management of T2D (more on this later).

More Protein for Better Glycemic Control

Glycemic control, or the aim of reducing and maintaining HbA1c, fasting glucose, and postprandial glucose toward normal levels, is critical to minimize the risk of T2D-associated morbidity and mortality.

Postprandial glucose fluctuations have been identified as an independent risk factor for cardiovascular events in T2D patients. Furthermore, evidence suggests that the size, frequency, and duration of these fluctuations (i.e. glycemic variability), may confer additional risks for the development of micro and macrovascular diabetic complications. 

Many factors can affect the postprandial glycemic response to a meal, but it is largely determined by the amount and type of carbohydrates consumed.

Diets reduced in carbohydrates can enhance glycemic control, and proteins are a viable substitute for carbohydrates.

Evidence for this statement comes from the work of Gannon et al. In this randomized crossover trial, subjects completed two five-week diet interventions. 

The macronutrient distribution of the high-protein diet was 40% carbohydrate, 30% protein, and 30% fat. For the control diet, the breakdown was 55% carbohydrate, 15% protein, and 30% fat. During each intervention, all food was provided to subjects, and body weight remained relatively stable. 

In the end, it was found that mean fasting glucose concentrations did not significantly differ between diets. However, there were statistically significant differences in HbA1c. During the high-protein diet, HbA1c decreased by an average of 0.8%. In comparison, it decreased by an average of 0.3% on the control diet.

Also, the high-protein diet resulted in a slightly greater insulin response at meals and a modestly lower postprandial glucose response, which amassed into a 38% decrease in the 24-hour integrated net blood glucose area response. 

Similar results were found in a recent short-term investigation. In this one, subjects underwent two 48-hour intervention periods. 

During one period, subjects consumed a high-protein diet with a macronutrient distribution of 31% carbohydrate, 29% protein, and 40% fat. The other diet, termed a “conventional diabetes diet,” featured 54% carbohydrate, 16% protein, and 30% fat.

All meals were weighed out and prepared by trained kitchen staff and diurnal glucose profiles were obtained using a continuous glucose monitor (CGM). Abdominal subcutaneous interstitial glucose level readings were collected in 5-minute intervals over each 48-hour period.

Glycemic control was assessed as mean sensor glucose level, postprandial glucose, mean of glucose readings over 4 hours post-breakfast and lunch, postprandial glucose excursions (i.e. magnitude of the postprandial peak post-breakfast and lunch), maximum and minimum sensor glucose, and area under the curve above a level of 140 mg/dL (glucose level rarely exceeded by healthy people) and 180 mg/dL (hyperglycemia as defined by the American Diabetes Association glycemic control targets).

In total, 576 measurements were obtained and It was found that the high-protein diet significantly improved the diurnal glucose profile and reduced all indices of glycemic variability by 36-45%. 

Again, it’s important to consider the fact that carbohydrates are the major factor in blood glucose control. Randomized controlled trials have demonstrated improved glycemic control along with reduced medication use in patients with T2D following low-carbohydrate diets, with greater glycemia improvements being generated in proportion to the reduction in carbohydrates.

As such, the reduction in carbohydrates may be primarily driving these outcomes, rather than the increase in protein. Nevertheless, protein has been shown to have beneficial effects on numerous hormones involved in regulating the postprandial glycemic response and is likely playing some sort of positive role. 

Protein is a potent insulin secretagogue and has little effect on blood glucose. This was demonstrated by early research, which showed that the ingestion of 50 g of lean beef in subjects with T2D led to marked increases in insulin concentrations, coinciding with not only stable blood glucose throughout the postprandial period but decreasing levels.

Other research has shown that dietary protein acts synergistically with ingested glucose to increase insulin secretion and reduce the glycemic response. Otherwise put, a more favorable glycemic response will occur when carbohydrate is consumed with protein than when it is consumed alone.

The reduced glycemia after protein consumption either with carbohydrates or alone may be due to increased insulin release but also to the release of gut hormones that delay stomach emptying and incretin hormones.

Incretin hormones are gut peptides that are secreted after nutrient intake and augment the secretion of insulin. 

High-protein diets are linked to increased secretion of the incretin peptides GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), which are known to be major determinants of blood glucose excursions

GLP-1, in particular, is pertinent because numerous clinical studies suggest that while the insulinotropic effect of GIP is markedly diminished in individuals with T2D, The GLP-1 secretion pattern remains largely intact and is comparable to that of healthy individuals.

GLP- 1 also slows gastric emptying and inhibits gut motility, and augments the first-phase insulin response.

First-phase insulin secretion involves the insulin normally secreted by pancreatic β-cells within 10 minutes after a sudden rise in plasma glucose concentrations. A prominent feature of T2D is a dramatic reduction in the first-phase insulin response. 

This defect is critical because first-phase insulin secretion is postulated to have the greatest effect on postprandial glucose excursions.

For these reasons, there has been great interest in developing methods by which GLP-1 action can be enhanced in patients with T2D to potentially fend off deterioration in β-cell function and prevent disease progression.

In one study, the effects of oral glutamine and whole protein low in glutamine on first phase insulin response and GLP-1 were examined in subjects with T2D.

In a randomized crossover fashion, subjects consumed either 25 g of L-glutamine supplemented with 16 g Philadelphia cheese (26 g protein, 5g fat, 152 kcal), 200 g low-fat cottage cheese (25 g protein, 2 g glutamine, 5 g fat, 182 kcal), or water after an overnight fast.

It was found that the first phase insulin response was blunted after water and augmented by the glutamine and cottage cheese interventions to a similar degree.

Also, glutamine was more efficacious in increasing GLP-1 concentrations 30 minutes post-ingestion, but total GLP-1 remained significantly increased after both conditions compared with water.

Overall, protein has a potent effect on GLP-1 and insulin levels leading to reduced postprandial hyperglycemia and increased satiety at meals. Consuming multiple protein-rich meals throughout the day can be a powerful tool for T2D management by improving the effectiveness of weight loss and glycemic control. 

With these points in mind, let’s take a look at some brand new research that examined the utility of high-protein diets for patients with T2D and prediabetes.

Putting It All Together: Direct Research

The first study of discussion was a randomized crossover trial and featured men and women with T2D. Each subject took part in two 6-week dietary interventions. 

During one period, subjects consumed a carbohydrate reduced high-protein diet (CRHP) with a macronutrient distribution of 30% carbohydrate, 30% protein, and 40% fat. The other diet was a conventional diabetes diet (CD) and consisted of 50% carbohydrate, 17% protein, and 33% fat.

All meals were provided to the subjects and both diets were designed to maintain body weight to diminish the confounding effects of weight loss and gain on the outcomes of interest.

The results of the trial demonstrated several benefits of a CRHP diet. There was a significant difference in fasting glucose at the end of the treatments (~150 mg/dL and ~158 mg/dL for CRHP and CD, respectively). There was also a significant difference in HbA1c. CRHP reduced HbA1c by 0.6% on average, while CD reduced it by 0.1%.

To add, The CRHP diet resulted in increased satiety, lower 24-hour mean glucose values, and significantly greater β-cell responsiveness to glucose following meals.

The authors reported that “amelioration of diurnal hyperglycemia in combination with the postprandial reduction in glucose in the present study using CRHP diet explain the improved β-cell function.”

To reiterate, these results took place with minimal changes in body weight. This corresponds with other research that reported a high-protein diet can significantly reduce liver fat in the absence of significant weight loss (a pivotal outcome considering the role of liver fat in the pathogenesis of T2D). 

These findings are especially compelling because they indicate that benefits can be obtained by adjusting the macronutrient distribution of the diet to a more even breakdown, even in the absence of weight loss.

Next, we have a very intriguing study featuring subjects with prediabetes. In this one, subjects were randomized to one of two dietary interventions for six months. 

The high-protein (HP) diet consisted of 30% protein, 40% carbohydrate, and 30% fat, while the high-carbohydrate diet (HC) was 15% protein, 55% carbohydrate, and 30% fat. Each diet featured a daily 500 kcal energy deficit and all food was provided to subjects.

The headline finding of this trial was that 100% of subjects in the HP intervention achieved prediabetes remission, while only 33% achieved this feat in the HC intervention.

Now, getting into the weeds, both diet groups experienced significant weight loss with no significant differences between groups. The HC diet led to an average reduction in fat mass of 3.55%, while the HP diet reduced fat mass by 2.49%. However, HP resulted in a 2.55% INCREASE in lean mass, while the HC diet led to a 3.02% DECREASE in lean mass.

Both diets resulted in significant decreases in the glucose area under the curve during an oral glucose tolerance test (OGTT), but the HP diet resulted in significantly greater reductions. Similarly, both diets significantly improved insulin sensitivity (HOMA-IR), β-cell function, and HbA1c, with greater improvements in the HP diet group.

During the OGTT, the HP diet group had a greater increase in plasma levels of GLP-1 and GIP. They also had significantly lower concentrations of ghrelin, suggesting that the HP diet was more effective at decreasing hunger.

The results of this trial bring attention to the paramount importance of weight loss for resolving metabolic dysfunction, but more importantly, they demonstrate the unique value of weight loss quality. 

The HC group lost more total weight, but experienced significant decreases in lean mass, while the HP group also lost a significant amount of weight, but increased lean mass in the process. This key difference ultimately led 100% of subjects in the HP diet group to achieve prediabetes remission.

In combination, the outcomes of these two trials provide evidence for the various potential benefits of a high-protein diet and support the idea that increasing protein intake can improve the management and prevention of T2D. 

Other Considerations – Protein Quality

At this point, we’ve established that increasing protein intake to roughly 30% of total daily energy intake can be an effective dietary approach for people with T2D, but what types of protein should that 30% be comprised of? 

In comparison to plant proteins, animal proteins are more efficient to achieve dietary essential amino acid requirements without the excessive ingestion of non-protein calories. However, while animal proteins have a superior amino acid profile, and as such, might be considered “higher quality,” there are other factors to consider in the context of T2D. 

Not all proteins are created equal in their ability to modulate insulin secretion and insulin sensitivity. Outside of the amino acid profile of a protein, its non-protein nutritional profile, bioactive properties, insulinogenic properties, and overall effects on glycemia should be considered.

A relationship between increased consumption of animal protein and T2D has been consistently observed in cohort studies. A caveat to this relationship is that it appears to be primarily powered by processed red meat consumption, rather than lean meat. Also, fish and shellfish have not been linked to T2D, while fatty fish may have a protective effect.

In contrast to animal sources, an inverse relationship between the consumption of plant proteins and T2D is typically observed.

The replacement of ≥ 35% of total daily protein intake with major sources of plant protein has been found to result in modest improvements in HbA1c, fasting glucose, and fasting insulin in individuals with T2D.

More specifically, nuts, soybeans, and pulses have all been shown to have beneficial effects on insulin sensitivity, and a number of mechanisms have been proposed to explain the positive effects of plant proteins on T2D management and prevention.

This includes an increased intake of L-arginine, fiber, and bioactive compounds, and reductions in body iron stores, dietary glycemic index, sodium and nitrite intake, and differences in fatty acid composition. 

Generally speaking, animal sources of protein that are rich in fat contain a larger percentage of saturated fatty acids (SFA) than plant proteins, and plant proteins tend to contain a higher percentage of polyunsaturated fatty acids (PUFA). SFA and PUFA are known to have differing effects on insulin sensitivity, with a benefit to consuming more PUFA. 

Together, these ideas suggest that it’s probably a good idea to consume a hefty chunk of total daily protein intake from plants. But what about other options? As alluded to, including some fatty fish in the diet is a good idea. Are there other animal-based sources of protein that have definitively positive effects?

Animal-based sources of protein contain the highest percentage of essential amino acids and leucine is a unique essential amino acid that is responsible for triggering muscle protein synthesis (MPS).

Following the initiation of MPS by sufficient leucine intake, the process is then limited by the availability of substrate, or additional essential amino acids. Fundamentally, proteins that contain high proportions of essential amino acids, and in particular, leucine (i.e. animal-based protein sources), are most effective in stimulating MPS

Furthermore, a serving of lean animal protein typically provides more or an equal amount of protein for significantly fewer calories than a serving of plant protein. 

These points suggest that per gram, animal-based protein sources are superior for increasing muscle hypertrophy and improving body composition.

Considering the potency of an energy deficit for managing T2D, and the value of skeletal muscle mass, animal-based sources of protein are an extremely useful tool to meet a high-protein intake with a limited number of calories.

Moving on to the “best” sources of animal protein for preventing and managing T2D, the body of evidence regarding low-fat, fat-free, and fermented dairy products have routinely reported an inverse association with T2D risk, with particularly strong outcomes for yogurt consumption.

In conjunction with these findings, other research has indicated that dairy foods and proteins (i.e. whey and casein) have a notable effect on glycemic control. There is ample evidence that dairy proteins increase the postprandial insulin response and lower the postprandial blood glucose response. 

The exact mechanisms to explain these outcomes have yet to be established, but it is believed that the amino acids and bioactive peptides derived from dairy proteins modify a physiological milieu, including delayed gastric emptying, and the enhancement of incretin and insulin responses.

Whey appears to be the more potent of the two dairy proteins. A plethora of studies has demonstrated that a whey protein pre-load within 30-minutes of a meal can markedly improve postprandial glucose in people with T2D.

Whey protein has also been observed to lead to greater insulin secretion and lower postprandial glucose concentrations than other proteins, such as ham, turkey, egg, and casein.

The greater insulinotropic effects of whey are thought to stem from its amino acid content. Whey is uniquely rich in branched-chain amino acids, and leucine, in particular. 

Leucine has been observed to be a special insulin secretagogue. Evidence for its distinct effects comes from research showcasing increased insulin response values after ingestion of casein protein plus leucine above that of casein protein alone.

Whey protein has been shown to augment the postprandial glucose response through other mechanisms as well, such as the secretion of gastrointestinal hormones that delay gastric emptying, including peptide YY and cholecystokinin (remember, GLP-1 also inhibits gastric emptying), and enhanced incretin secretion (i.e. GLP-1 and GIP).

It’s speculated that enhanced incretin secretion is due to the inhibition of dipeptidyl peptidase-4 (DPP-4) action by whey-derived peptides. Once entering the plasma, GLP-1 and GIP are degraded rapidly by the enzyme DPP-4. Thus, the inhibition of DPP-4 could increase the half-life of GLP-1 and GIP, leading to improved glucose control.

To wrap-up, both animal and plant protein sources are viable options for preventing and managing T2D, and a healthy mix of both is recommended due to their distinct properties. For animal proteins, specifically, the consumption of dairy products should be emphasized, while the consumption of red processed meat should be kept to a minimum.

Conclusion

While high-protein diets have been a mainstay of bodybuilders for several decades now, their popularity in the general population has tended to wax and wane. 

As a result of rising rates of obesity and its complications, there has been a surge of interest in high-protein diets for weight loss and treating cardiometabolic disease due to their unique benefits.

Increasing protein intake can improve weight loss effectiveness by mitigating increases in appetite and preserving skeletal muscle mass. It can also improve glycemic control through its effects on insulin and incretin secretion, and gastric emptying.

Based on the current evidence, a diet that features 25-30% of total daily energy intake from protein is a viable option to improve the prevention and management of T2D.

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