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The wheys of weight loss

Harnessing the ability of proteins to reduce appetite is important for developing efficacious weight-loss products. Robert Child, PhD, investigates how different proteins are digested at different rates, and which have the best satiety-inducing effects, making them ideal to incorporate into the next generation of finished foods

The classic problem for people attempting to lose weight by calorie restriction is that it is associated with feelings of hunger. This often results in binge eating, poor dietary adherence and the consumption of excess calories, which are ultimately stored as body fat. The Atkins diet is unusual as it allows dieters to eat as much food as they desire without exercising. This weight loss seems to be associated with an increased satiation and therefore a decreased food intake. The typical diet involves replacing carbohydrates with high-protein and high-fat foods — the same foods demonised as the causes of obesity!

Scepticism about the diet?s ability to produce weight loss using isocaloric calorie diets have been replaced with curiosity in the academic community, especially as initial subjective reports have been backed up with rigorous scientific research.1,2,3,4,5

One recent study in particular addressed many criticisms of earlier studies on low-carb diets, yet produced similar findings.2 Foster and co-workers assigned obese men and women to one of two diet groups for 12 months. One group was given a copy of the Dr Atkins? New Diet Revolution and asked to follow the diet as described. The second group was asked to follow a low-calorie diet providing 1,200-1,500kcal per day for women and 1,500-1,800kcal per day for men. The diet contained 60 per cent carbohydrates, 25 per cent fat and 15 per cent protein by energy and was based on the Food Guide Pyramid. The experimenters purposefully minimised interventions from health professionals, to mimic what happens during normal dieting.

After three months, Atkins participants lost an average of 17.5 pounds compared with 8.2 pounds in the conventional group. After six months, progress in subjects following the Atkins diet slowed down. They lost an average of just 3.5 pounds between the third and sixth months of the study, for a total weight loss of 21 pounds. However, they were still doing better than the low-fat group, which lost 2.8 pounds between the third and sixth months of the study, for a total weight loss of 11 pounds. After 12 months both groups had regained some of the lost weight.

Participants following the Atkins diet regained roughly five pounds. Those on the low-fat diet regained an average of 1.3 pounds. Over the whole year, subjects on the Atkins diet lost an average of 15.8 pounds, compared to 9.7 pounds in the low-fat group. The responses to both diets are shown in Figure 1.

The key factor that appears central to the effectiveness of diets with increased protein contents is that people following such dietary regimes feel less hungry.6,7,8,9,10,11,12 As a consequence, they consume fewer calories, making it easier to generate the negative energy balance necessary for fat loss.6,13 If nothing else, the controversy surrounding the Atkins diet has highlighted the importance of controlling appetite when attempting to lose weight.

How is appetite regulated?
Harnessing the ability of specific nutrients to reduce appetite is important for developing efficacious weight-loss foods. Research conducted over the past 50 years has revealed an eating control system of enormous complexity.14 In response to food intake, specific hormones and peptides are released by the upper intestine.15,16 These act upon gastrointestinal or hepatic receptors, which relay messages to the brain via the afferent vagus nerve. Some of these appetite factors also appear to act directly upon specific brain regions, primarily the arcuate nucleus and hypothalamus.15,17

The first appetite-suppressing peptide factor scientists identified was cholecystokinin (CCK). Several other peptides also modulate feeding, including gastrin inhibitory peptide (GIP), which suppresses appetite,15 and the hormone glucagonlike peptide 1 (GLP-1), which promotes satiety and reduces energy intake.18

Considering the complexity of central and peripheral satiety mechanisms, appetite probably represents the integration and summation of each factor?s individual effects. As a group, appetite factors provide a number of potential leads for drug development; however, comparatively poor understanding of appetite control mechanisms currently makes pharmacological approaches problematic.17,19

In contrast, it has long been recognised that high-protein foods are generally more filling than equivalent isocaloric high-fat or high-carbohydrate meals.11,20,21 There is evidence suggesting that increased dietary protein intake can help weight loss by improving glucose regulation and insulin sensitivity.22 However, co-ingestion of protein and carbohydrate can also result in greater elevations in insulin than isocaloric meals containing only carbohydrates.23,24

In 2002, a systematic literature review comparing the effects of low glycaemic index (GI) foods and diets on satiety, energy intake and weight loss concluded ?There is no evidence at present that low-GI foods are superior to high-GI foods in regard to long-term body weight control.?25 In contrast, a separate review proposed that short- and medium-term studies generally showed an inverse relationship between satiety and GI.26 In addition, the authors concluded that medium-term trials found less weight loss on high-GI or high-glycaemic-load diets. They considered these effects, coupled with the association of high-GI foods with cardiovascular disease and type 2 diabetes, were sufficient to recommend low-GI foods to obese populations.26

It is currently unclear if modification of the GI response by increased protein intake is an important contributor to satiety and weight loss. It is clear that high-protein foods provide the industry with a comparatively inexpensive and effective way to generate appetite suppression. Such effects are of major importance for the formulation of effective weight-loss products.

Digestion rate and appetite
Gastric emptying, luminal hydrolysis and mucosal amino acid absorption are considered the main steps that limit (ie, slow) the digestion of proteins.27 Of protein sources, whey protein — the fluid portion of milk obtained by coagulating and removing curd — rapidly enters the jejunum, mostly in the form of intact proteins. In contrast, casein is slow to appear and does so mainly in the form of degraded peptides. These differences are largely attributed to the high solubility of whey protein and clotting and/or precipitation of casein in the acidic media of the stomach.27

In recognition of these differences, the terms ?fast? and ?slow? dietary proteins were introduced to respectively describe the differences in the digestion rates of whey and casein.27 Figure 3 is based on the original data from this study, showing the peak in plasma leucine levels after the whey meal was more than double that of the casein meal. As both meals had identical leucine contents, this indicates faster digestion.

Although some complex carbohydrates and fat typically increase the time for gastric emptying and slow digestion,28,29 recent research has shown that whey is still digested faster than casein in the presence of these macronutrients.30,31 The faster digestion of whey relative to other proteins is not simply academic, as this characteristic makes whey more suitable for appetite control than many other proteins.

Studies comparing whey protein and slow-digesting casein found that the fast-digesting protein produced the greatest satiety
Intuitively, slow-digesting proteins like casein would be anticipated to be more suitable for weight-loss foods, as this would be expected to prolong feelings of fullness. In practice this does not appear to be the case, as several studies have shown that fast-digesting whey protein is more satiating than casein. 31,32

Appetite effects compared
Satiety, also referred to as ?fullness,? is an important regulator of appetite. The magnitude of the satiety response to food regulates how much is eaten at a single meal, in effect determining if you feel you have ?room? for pudding. The duration of the satiety response determines how long after eating you desire the next snack or meal.

Until very recently, it was not clear if all proteins produced the same level of satiation. One study found no difference in the satiating ability of a variety of slow-digesting proteins including egg albumin, calcium caseinate, gelatin, soy protein concentrate, pea protein isolate and wheat gluten concentrate.33 A separate study evaluated the satiating effects of different meats, all of which were digested more slowly than whey.34 Fish protein was found to produce greater satiety than beef or chicken, resulting in greater increases in plasma taurine and methionine and a change in the ratio of tryptophan to branched chain amino acids. Based on the time taken for plasma amino acids to peak, the digestion of fish appeared slower than beef or chicken and the authors proposed that this might have contributed to greater satiety.

In contrast, studies comparing whey protein and slow-digesting casein found that the fast-digesting protein produced the greatest satiety.31 The effects of protein digestion rate on satiety is a speciality of professor Joe Millward, head of the Division of Nutrition and Food Safety at the University of Guildford in the UK. In two seminal studies, Millward and co-workers compared the effects of a fast-digesting whey isolate and slow-digesting casein meals on appetite and energy balance.31 Two hours after a standardised breakfast, a 1,672kJ meal was provided, containing 48g of either whey or casein. The whey meal resulted in significantly less hunger and at a subsequent meal, reduced energy intake 19 per cent (861kJ) more than the casein meal.

In a second experiment, 1,700kJ meals containing either 48g of whey or casein were provided 3.5 hours after a standardised breakfast. Relative to casein, the meal containing whey resulted in a greater reduction in the desire to eat and greater sensations of fullness. The biochemical responses underpinning these findings appear to be caused by greater increases in the satiety factors GIP, GLP-1 and CCK, after the whey meal.31 Figure 2 provides a schematic diagram demonstrating possible mechanisms through which these effects might have occurred.

Safety concerns
Several studies demonstrate that slightly increasing protein intake — about 1.5 times the RDA — facilitates weight and fat loss.1,2,35 Typically, the use of such diets to help weight and fat loss are countered by concerns of negative effects on kidney function.36,37 Skov and co-workers reported that ?high? protein intakes of around 110g per day were without adverse effects when consumed over a six-month period.38

More long-term analyses showed no association between protein intake and kidney problems during ageing.37,39 In addition, no negative effects on kidney function are seen with long-term daily protein intakes ranging from 1.2-2.0g per kilogram of bodyweight, about 90-150g per day.40

Renal clearance is highly efficient with daily protein intakes up to 3g per kilogram of bodyweight, around 225g per day.41 These data indicate that increasing protein intake to levels up to three times the RDA are without adverse effects on renal function, providing there is no pre-existing liver or kidney disease. Furthermore, much lower protein intakes of 1.5g per kilogram of body weight per day are sufficient to produce weight loss effects and could be considered beneficial to health.

In reference to increased protein intakes to facilitate weight loss, Jill Scott, co-ordinator of the British Dietetic Association?s Weight Wise campaign, commented, ?This increase in protein intake is acceptable, but it would be nice if there were more long-term studies.?42 She went on to suggest that ?the British Dietetic Association currently places a major emphasis on simply eating a balanced diet, as there are concerns about the increase in dietary fat intake normally associated with high-protein diets.?

Despite the common preconception that high-protein diets and/or low-carbohydrate diets increase risk factors for cardiovascular disease, experimental data shows the opposite. Low-carb diets have been found to reduce blood triglycerides,2,4 improve HDL cholesterol,1,2 and increase markers of insulin sensitivity.1,43 It is important to note that all of these beneficial changes were greater than those observed in control subjects, who followed conventional high-carbohydrate weight-loss diets.

The scientific literature indicates that protein can safely be consumed at levels two to three times higher than the RDA. It also has a low-calorie density, as a gram of protein provides only 17J of energy, similar to that of carbohydrates, but less than half that of fat.44 Protein also produces greater satiety than carbohydrates or fat.11,20,21 When considering these effects together, there is a strong rationale to recommend high-protein foods to facilitate weight and fat loss. The Foods Standards Agency and British Dietetic Association currently place a major emphasis on increasing dietary carbohydrate intake to facilitate fat loss.12,45,46,47 The available evidence suggests that to combat obesity more effectively, this advice should be revised to favour diets with a higher protein and lower carbohydrate content.

Proteins for Atkins foods
The high-fat content of the Atkins diet, combined with low levels of fibre and vitamins, have raised concerns with health professionals and the public regarding the diet?s safety. Although many of these concerns are without a sound scientific basis, it is prudent to take a multivitamin and mineral supplement that meets the RDA for these nutrients. In addition, consuming foods rich in fibre such as bran and husks could provide specific health benefits, without reducing the efficacy of the Atkins diet.48,49

The fact that for the same energy content, protein is more satiating than carbohydrate or fat should not be ignored and is fundamental for the formulation of effective weight-loss foods. The greater thermic response of proteins relative to other macronutrients also helps generate a negative energy balance and produce weight loss.12,50,51,52,53,54 Increasing dietary protein intake when consuming hypocaloric diets increases the rates of weight and fat loss relative to conventional weight-loss diets.35 Increased protein diets also result in better maintenance of muscle mass, especially when the weight-loss program also involves exercise.35 Because muscle has a high metabolic rate, this muscle-sparing effect could act catalytically to facilitate even more rapid reductions in body fat. The next generation of weight-loss foods could harness the beneficial effects of the Atkins diet while simultaneously addressing health concerns relating to its fat, fibre and vitamin content. There are a number of potential protein sources available to food manufacturers that wish to produce low-carbohydrate weight-loss products. Different proteins have very different functional effects, which can profoundly influence the efficacy of weight loss and diet foods.

The high satiating effect of fish could be useful in foods to help weight loss. However, the strong characteristic fish flavour and comparatively high incidence of fish allergies in Westerners could limit its applications even in savoury products.55

Soy protein provides more flexibility, being easy to incorporate into sweet and savoury foods. It is well tolerated and ideal for people with lactose intolerance, although soy can impart beany flavours, and can give a gritty texture to drinks and a powdery texture to foods.56

In contrast, casein and whey have comparatively bland tastes and can easily be incorporated into foods. When used in nutrition bars, casein typically provides a softer texture than whey. In contrast, whey?s greater solubility makes it ideal for ?instant mixing? drinks. The greater satiating effect of whey protein relative to slow-digesting proteins like casein also provides an advantage for appetite control and potential benefits for weight loss.31,32

Commercial whey products can provide in excess of 20 per cent total protein caseinomacropeptide, which is also referred to as glycomacropeptide.57 During the formation of cheese curd, caseinomacropeptide (CMP) is cleaved by the enzyme chymosin, making it water soluble. This allows it to move from the curd into the whey protein fraction.58 CMP promotes CCK release in humans,59 and it has been proposed that the ability of whey to produce greater satiety than casein is due to differences in CMP content.58 Studies administering 0.4-2g of CMP to humans failed to find any effects on food intake an hour later.60 However, even at the highest CMP dose, this would only have provided the same amount of CMP as 10g of whey protein.

Laboratory studies have shown that a whey isolate bolus of 39g produces superior satiety relative to carbohydrate and 48-50g of whey isolate significantly reduces food intake relative to casein.11,31,32 The work of Gustafson and associates suggests that consuming a whey bolus of less than 10g may be insufficient to reduce appetite, although whey with a high CMP content may have greater efficacy for producing satiety.60

It is also important to note that whey isolates produced by ion exchange have a very low CMP content, which may reduce their ability to increase satiety and suppress appetite.61 The optimal amount of whey required to increase satiety and reduce food intake has not been established. The weight-loss benefits that arise from increasing protein intake from 1.0g per kg bodyweight per day to around 1.5g per kg bodyweight per day indicate that increasing protein intake by around 40g daily is sufficient to facilitate fat loss.1,2,35

When considering the greater appetite-suppressing effect of whey relative to other proteins, it is possible a smaller amount of whey could produce the same effects. Based on Gustafson?s work, appetite-suppressing effects might be lost with a whey bolus of less than 10g.60 Therefore, the prescription of foods providing a 15-20g whey bolus, twice daily, appears a useful starting point for weight-loss products.

Dairy proteins could also facilitate fat loss by providing large amounts of bioavailable calcium, which is proposed to stimulate fat mobilisation from adipose tissue.62,63

Opportunities abound
The latest research on a variety of proteins has revealed exciting applications for appetite control. Opportunities already exist for suppliers and product manufacturers to develop cost-effective and efficacious fat-loss products. Such developments could be particularly timely for the US and UK, where recent legislative changes have outlawed many stimulant-based weight-loss supplements.

The available research suggests that whey is the most effective protein for reducing appetite and energy intake. However, the ideal choice of protein for weight loss in foods will also be dependent upon the food matrix in which it is presented. The excellent solubility and neutral taste of whey protein, coupled with its low fat and carbohydrate content, make it suitable for a wide range of applications in weight-loss foods, including yoghurt, ice cream, mousses and other desserts.

The UK?s Committee of Advertising Practice assesses marketing claims relating to functional foods. This independent regulatory body has already accepted claims that could be used to drive consumer interest in whey-based weight-loss products.

Robert Child, PhD, is a nutritional biochemist and CEO of Alimentarius Ltd. The company specialises in the development of functional foods and nutraceutical products and obtaining advertising approval for health claims. Respond:
All correspondence will be forwarded to the author.

Dairy enters the healthy beverage category
Functional beverage sales in 2004 were estimated at $10 billion, an annual increase of 11 per cent, according to the Mintel Group. Dairy ingredients are being looked at by formulators because they naturally feature protein, essential amino acids, calcium, potassium, and other vitamins and minerals.

Key trends for dairy beverages include:

  • Higher-protein, lower-carb versions of dairy standards. Ultrafiltration, a sieving process that can remove lactose, soluble minerals and water from milk, is gaining importance as consumers look for more protein and fewer carbs from beverages, a trend Mintel says has moved from foods to beverages. Ultrafiltered milk is the base for many reduced-calorie and lower-carb dairy products.
  • Drinkable yoghurts and smoothies. The segment may double by 2008. Yoghurt is an excellent vehicle for probiotics. Stonyfield Farm touts the six live active cultures in its Organic Yogurt Smoothies as part of a ?proactive approach to good health.? Whey, ultrafiltered milk and dairy calcium can help target these products to more specific consumer segments.
  • Protein-enriched energy beverages. Gatorade is testing a whey-enriched beverage, G-Slide Smoothies, targeted at growing athletes. Whey proteins can improve a beverage?s protein profile, adding clean flavours that do not require masking. Whey proteins build lean muscle mass after exercise.
  • Meal replacements and meals-to-go. Americans now eat at least one meal in five in the car. The $2.3 billion-a-year meal-replacement industry has responded to dashboard diners with products that offer more protein, vitamins, minerals and fibre, but fewer carbs and calories. UF milk is a natural ingredient for ready-to-drink meal replacements.
  • Performance waters. This burgeoning segment accounts for 10 per cent of the overall beverage market. Whey protein and dairy calcium can be used for nutritional enrichment of water for beverages that go beyond quenching thirst.
  • Blended beverages. Dairy?s affinity for fruit flavours makes it a perfect partner for blending with juices to create products with the benefits of both. Dean Foods is offering Land O? Lakes 80 ?N Sunny — a blend of low-fat milk and fruit juice as an alternative to soda and fruit drinks.

—Bill Haines

Bill Haines is vice president of product innovation at Dairy Management Inc. 1-800-248-8829. DMI?s two applications labs, six dairy research centres, and experts in research, technology, applications, nutrition and marketing can help manufacturers bring dairy-based products from concept to marketable product.

The whey-to-go protein
Despite some similarities in amino acid composition between whey, casein and soy, (See Table 1 below) there are many important differences. These include a much higher content of the branched chain amino acids (BCAAs), especially leucine, which could facilitate glucose regulation.1 Whey is a by-product of hard cheese manufacture and, though nutritious, has limited application as a food ingredient in this form.

Heating and acid precipitation can be used to purify whey to produce concentrates with a protein content above 85 per cent. However, these treatments also denature some of the bioactive proteins so that their functional properties may be lost.2,3 For example, Cabet and Holst found that a whey isolate heated to 85oC was digested at the same slow rate as casein.4 Heating whey protein is known to reduce the content of key functional proteins, such as beta-lactabumin, and reduces overall protein solubility.5

Passing whey through a series of filters can produce whey isolates with a protein content of around 90 per cent, without the use of heat or strong acids. This process is often referred to as cross-flow microfiltration, which minimises denaturation of proteins. This allows important functional characteristics such as fast digestion to be retained. Specific protein fractions can be further purified using a combination of cross-flow microfiltration and ion exchange chromatography. However, ion exchange whey proteins may be less effective at producing satiety because this process reduces the normal CMP content from around 20 per cent to very low levels.6

Based on the available scientific evidence, manufacturers wishing to use whey in weight- loss foods should use non-heated whey protein isolates to minimise protein denaturation. Non-ion exchange whey protein isolates are preferable, due to their comparatively high CMP content. Non-heated whey protein isolates, which are not produced by ion exchange, appear to have distinct advantages over other proteins such as casein and soy.


Typical amino acid composition of whey, casein and soy isolates
(Values are expressed per 100g of product)

Amino acid












Aspartic acid








Glutamic acid












Isoleucine* +




Leucine* +




































Valine* +




* Essential amino acid
+ Branched chain amino acid

Will healthier ingredient integration trim the masses?
Professor Joe Millward is head of the Division of Nutrition and Food Safety at the University of Guildford, UK. He holds a leading position in appetite control research, so was the obvious choice to answer some questions about this rapidly developing area.

FF&N: Your studies on satiety effects show a greater reduction in food intake following the whey as opposed to the casein meal. Instinctively, we think of casein as clotting in the stomach and promoting a feeling of fullness. What are your thoughts on this?

JM: Amino acid flux is important in appetite regulation, and we see bigger changes in plasma amino acids after a whey meal than after a casein meal.

FF&N: Will the changes in plasma amino acids have an influence on brain neurotransmitters, and are branched chain amino acids (BCAA) still considered important in appetite control?

JM: The BCAA serotonin hypothesis has been blown apart. It is likely amino acid flux has some influence on the brain, but at the moment we don?t know what it is — and I don?t know of any other mechanism by which BCAAs influence neurotransmitters.

FF&N: With the relative lack of understanding of appetite control, is the pharmaceutical industry wasting its time trying to produce a diet pill, especially when there are functional foods available that reduce energy intake?

JM: I have a real problem with the single-bullet approach; it goes against all that we know about appetite. It is a multifaceted and highly complex system and the pharmaceutical industry has been naive. Targeting a single pathway in an attempt to regulate appetite can have severe and undesirable outcomes. We already know that protein reduces appetite — that?s why the Atkins diet works.


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Whey-to-go protein references
1. Layman. The role of leucine in weight loss diets and glucose homeostasis. J Nutr 2003; 133:261S-267S.
2. Bounous and Gold. The biological activity of undenatured dietary whey proteins: role of glutathione. Clin Invest Med 1991; 14:296-309.
3. Kinsella and Whitehead. Proteins in whey: chemical, physical, and functional properties. Adv Food Nutr Res 1989; 33:343-8.
4. Calbet and Holst. Gastric emptying, gastric secretion and enterogastrone response after administration of milk proteins or their peptide hydrolysates in humans. Eur J Clin Nutr 2004; 43:127-39.
5. Mangino et al. The effects of heating during processing on the functionality of whey protein concentrates. J Food Sci 1987; 52:1522-4.
6. Wang and Lucey. Use of multi angle laser light scattering and size-exclusion chromatography to characterize the molecular weight and types of aggregates present in commercial whey protein products. J Dairy Sci 2003; 86:3090-101.

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