Promoting Satiety, Curbing Appetite Naturally

People will try anything to control their weight. The market is littered with diet products professing endless ways to make or keep people lean. However, a recent survey of U.S. and Brazilian women (sponsored by DSM Food Specialties) revealed appetite reduction was the number one preferred means of weight management. In fact the claim “Reduces your appetite” scored particularly high for appeal, relevance and credibility. Ingredient suppliers are working hard to give diet consumers science-backed products with appetite-suppressing results.

Survival requires appetite. Much like thirst keeps us in hydration mode, hunger reminds us of our never-ending quest for fuel and energy. As with most body systems, this one managing food intake and weight relies on checks and balances. Thus, hunger and satiety—fullness—perform a tag team routine carefully choreographed by biochemicals in the gut and central nervous system (CNS).

Giving credence to the blame hormones get during foodfrenzies in pregnant women, these chemical messengers are produced in the digestive system and signal the brain to eat or not to eat. When it comes to controlling appetite and satiety via nutritional compounds, ingredients often target the production and activity of these hormones.

The “hunger hormone,” ghrelin, is produced in the stomach, with increased levels before a meal and decreased levels after a meal. Ghrelin heads to receptors in the brain, including the hypothalamus, which controls metabolism, and the midbrain, which controls reward and pleasurable food associations.

As evidence of the effect that a lack of sleep can have on appetite and weight gain, ghrelin levels increase due to short sleep duration, thereby increasing appetite. However, other health conditions greatly affect ghrelin production and levels, making weight control a challenging feat. Levels of ghrelin are high in anorexia suffers, indicating appetite skyrockets in the face of starvation. While anorexics ignore this signal due to mental illness, the average starvation dieter usually succumbs to the hunger, negating any dieting achievements.

While increased ghrelin levels spark appetite and food consumption, other transmitter compounds help keep hunger and eating in check. In the small intestine, the peptide cholecystokinin ( CCK ) helps digest fats and protein. This neurotransmitter connects with CCK receptors in the CNS and, in addition to prompting other reactions (anxiety and nausea), can promote satiety and curtail appetite. The effect of CCK is considered brief, but two other peptides, glucagonlike peptide-1 (GLP-1) and peptide YY (PYY), help signal fullness in the brain and in the stomach, which slows movement of food in the gut, ensuring maximum digestion of nutrients and deceased appetite.

A high-protein/low-carb diet has been credited with weight management benefits, and the mechanism may be partly due to its ability to affect these satiety hormones. In fact, according to 2006 research from Zeist, protein may be the most satiating macronutrient.¹ The researchers found a high-protein breakfast decreased postprandial ghrelin concentrations more strongly over time than a high-carb breakfast; they noted strong associations between ghrelin, glucose-dependent insulinotropic polypeptide and glucagon suggest stimulation of these peptides may mediate the postprandial ghrelin response.

It appears all forms of protein can be helpful in this pursuit of satiety. University of Toronto scientists reported whey, soy and gluten preloads in both lean and overweight boys decreased food intake three hours later, compared to glucose preload.² They theorized postprandial ghrelin, GLP-1, insulin and CCK may contribute to this post-protein satiety, adding GLP-1 concentrations were increased in overweight subjects, which may have contributed to satiety responses in this group.

Another comparison of protein forms, this time casein and whey, resulted in reduced appetite and energy intake for each form.³ Overweight men taking liquid preloads of one of the protein forms or either lactose or glucose were tested for plasma ghrelin, CCK , insulin, glucose and amino acids, gastric emptying rate (plasma paracetamol), appetite rating (visual analog scale), and ad libitum energy intake. Glucose led to increased energy intake, compared to the protein and lactose preloads and relative to ghrelin levels. However, CCK was 71-percent higher 90 minutes after the protein preloads, compared with glucose and lactose; this translated to increased satiety and reduced appetite.

One component of whey and casein that gained considerable attention was glycomacropeptide, which is known to stimulate CCK . A University of California, Berkeley, trial tested several different combinations of whey, whey protein isolate and glycomacropeptide on satiety and CCK levels.⁴ Subjects taking the protein preloads were tested at six different time intervals, up to 105 minutes post-preload. Pre-meal satiety was greater after whey protein preloads compared to control and glycomacropeptide-only preloads in women, but not in men. In a similar pattern, CCK concentrations predicted the subjective satiety in women, but not in men. The researchers concluded: “[Glycomacropeptide] alone is not critical in pre-meal whey-induced satiety; however, it may have a unique role in compensatory intake regulation managing daily energy intake.”

While the investigation into glycomacropeptide’s mechanism of action in weight management continues, research results showing benefits have been reported. In 2006, Satietrol®, a glycomacropeptide-based ingredient from PacificHealth Laboratories, produced a significant reduction in food intake in a proprietary trial. Designed to suppress appetite by activating CCK , Satietrol was administered in the double blind, placebo-controlled study as a soft chewable tablet or placebo to overweight subjects with an average body mass index ( BMI ) of 28, prior to an openended meal. Results showed individuals given Satietrol demonstrated a 20-percent reduction in caloric intake compared to the placebo group.

Whether owing to glycomacropeptide or other peptides, protein appears to produce results in appetite leading to weight control. Researchers from the Rowett Research Institute, Aberdeen, Scotland, verified a low-carb, high-protein, ketogenic diet reduces hunger and lowers food intake significantly more than high-protein, medium-carb nonketogenic diets do.⁵ But a low-carb diet on its own has shown a benefit to dietary hormones. In a 2007 research report, 18 obese men and women were randomly assigned initially to one week of a weight-maintenance low-carb/high-fat (LCHF) or low-fat/high-carb (LFHC) diet and were measured for YYP levels 2.5 hrs later.⁶ Tests showed the LCHF diet stimulated PYY secretion more than the LFHC diet.

As far as macronutrients affect appetite science, both soluble and insoluble fibers have generated positive effects on satiety and hunger hormones. University of Toronto researchers reported compared to low- and zero-fiber cereals, a serving of cereal with 33 g insoluble fiber reduced appetite, lowered food intake and reduced glycemic response to a meal consumed 75 minutes later.⁷ Insoluble fiber also benefits appetite control in hospital patients receiving enteral formulas for nutrition—which can affect appetite. In a King’s College London trial, patients were given either standard enteral formula or one containing 10 g/L pea fiber and 5 g/L fructooligosaccharide (FOS) insoluble fiber.⁸ Consumption of the pea-fiber/FOS formula resulted in higher mean fullness, minimum fullness and minimum satiety, compared to the standard formula.

Soluble fiber has made a similar impact on appetite and satiety. Louisiana State University researchers reported 14 weeks of treatment with 4 g/d oat and barley beta-glucan soluble fiber (as ViscoFiber®, from Cevena Bioproducts, now Natraceutical Canada) along with a lifestyle change program and dietary restrictions, resulted in weight loss and increases to fasting PYY, fasting GLP-1 and satiety at one hour following a standard meal.⁹

A soluble fiber, glucomannan, derived from the root of the elephant yam or konjac plant, has also shown promise in promoting satiety. A Spanish investigation of a fiber mixture containing 1 g glucomannan and 3 g Plantago ovata husk taken twice (bid) or three times daily (tid) outperformed placebo in promoting postprandial satiety among 200 obese or overweight patients.¹⁰

Micronutrients also play a role in satiety. In 2007, researchers from Laval University, Quebec, conducted a two-study investigation on multivitamin consumption and weight/appetite.¹¹ In the first study, body weight and composition, energy expenditure and data scores from the Three - Factor Eating Questionnaire completed by consumers of micronutrients and/or dietary supplements were compared to multivitamin non-consumers. Results showed male multivitamin consumers had lower weights, body mass index ( BMI ) and fat mass than did non-consumers; the results were less significant in females. However, female supplement consumers had lower disinhibition (inability to manage impulses) and hunger scores. In the second study, these same variables and appetite ratings (visual analogue scales) were measured in 45 obese non-consumers of supplements, who were randomly assigned to a double blind, 15-week energy restriction (- 2,930 kJ/d) diet combined with a placebo or with a multivitamin and mineral supplement. While weight loss was similar between both intervention groups, fasting and postprandial appetite ratings were significantly reduced in multivitamin and mineral-supplemented women.

Addressing various factors in weight management, the micronutrient mineral chromium may limit appetite, especially relative to carb control. In a randomized, double blind, placebocontrolled clinical trial, test subjects were supplemented with 600 mcg/d chromium picolinate (as Chromax®, from Nutrition 21) or placebo.¹² In a subset of 113 individuals with atypical depression, who reported the highest levels of carbohydrate cravings , scored better than placebo subjects on four items on the Hamilton Depression Rating Scale (HAM-D-29), a scale commonly used to measure symptoms in depressed patients; the four HAMD-29 items included carbohydrate craving, appetite increase, increased eating and mood variation throughout the day. Analysis showed 65 percent of patients supplementing with Chromax showed significantly greater improvements on total HAM-D-29 scores, compared to only 33 percent of placebo patients. Researchers suggested chromium’s primary benefit was on carbohydrate craving and appetite regulation in depressed patients, and 600 mcg of elemental chromium may be beneficial for patients with atypical depression who also have severe carbohydrate craving.

Special Satiety Solutions

While macro- and micronutrient dietary components show effects on appetite, satiety and the hormones that regulate these urges, the race to find other compounds in nature that might make good supplemental tools for weight control has uncovered many specialty ingredients.

CCK is released in the upper part of the small intestines and is largely induced by protein and fat intake, especially long chain polyunsaturated fatty acids. The Korean pine tree (Pinus koraiensis) produces nut oil especially rich in long-chain fatty acids, such as pinolenic acid, which appears to suppress appetite via hormone regulation. Proprietary research on pinolenic acid (as PinnoThin™, from Lipid Nutrition) showed 3 g/d of the compound controlled hunger by stimulating the release of the hormones CCK and GLP1, which is also fat-dependent. In 2006, Lipid Nutrition published a study in FASEB Journal on 18 overweight women ( BMI =25 to 30) receiving capsules with 3 g PinnoThin or olive oil (placebo) in combination with a light breakfast.¹³ At six time intervals from zero to 240 minutes, blood samples were analyzed for CCK and GLP1 and appetite sensations were evaluated by using visual analogue scales. The intervention significantly induced CCK after 30 minutes and GLP1 after 60 minutes, relative to placebo. Over a period of four hours, plasma CCK was 60-percent higher and GLP1 was 25-percent higher in response to PinnoThin than in response to placebo. In the end, PinnoThin affected appetite sensations during the four hours following intake. Researchers noted at 30 minutes the “desire to eat” and the “prospective food intake” scores were 29- and 36-percent lower relative to placebo, respectively.

A protein extract from potatoes (as Slendesta™, from Kemin Health) also acts on CCK levels to help control hunger. A series of proprietary studies conducted at Iowa State University show proteinase inhibitor II (PI2) from Slendesta promotes satiety and weight-loss. One study, a randomized, placebo-controlled, crossover clinical, found participants (n=45) taking Slendesta before a meal experienced significantly greater fullness and a decreased motivation to eat. Further, CCK levels rose and remained elevated for a longer period of time post meal in those taking Slendesta than in the placebo group.

In the largest randomized, double blind, controlled clinical study, 240 participants consumed either 300 mg or 600 mg of Slendesta (providing 15 mg or 30 mg PI2, respectively) or a placebo approximately 60 minutes before their two largest meals. Slendesta provided statistically significant reductions in weight, waist and hip measurements at 12 weeks for both doses, compared to placebo. An open label study featured supplementation with 300 mg to 600 mg Slendesta 60 minutes before two largest meals by 28 healthy adults ( BMI =25 to 35) for 12 weeks and in 15 healthy adults for an additional eight weeks. Results showed significant weight loss at each four-week visit and statistically significant reductions in waist and hip measurements and waist-to-hip ratios from eight weeks to study completion.

Taking a different approach, hydroxycitric acid ( HCA ) targets the protein leptin, another satiety hormone. Leptin is produced by body fat and binds to receptors in the hypothalamus where it inhibits peptides that signal to increase appetite. A 2002 Maastricht University, Netherlands, trial in overweight men and women discovered HCA treatment reduced 24-hour energy intake in humans, while sustaining satiety.¹⁴ Then a 2005 Georgetown University Medical Center, Washington, study investigated HCA (as Super CitriMax®, from InterHealth Nutraceuticals) on appetite, including leptin.15 Researchers randomly divided 90 obese adults into three groups and were given either a daily dose of 667 mg HCA (providing 2,800 mg/d HCA ); a 4,667 mg dose of a combination of HCA , 4 mg niacin-bound chromium (as ChromeMate®, also from InterHealth) and 400 mg Gymnema sylvestre extract (providing 100 mg gymnemic acid); or a placebo. The combined results showed HCA and, to a greater degree, the combination of HCA plus chromium and gymnema not only reduced body weight and BMI , but also suppressed appetite and increased serum leptin levels more than placebo.

In 2005, research unveiled at the annual meeting of the Federation of American Societies for Experimental Biology (FASEB) further specified the action of HCA on appetite control. In the in vitro study, researchers examined slices of rat hypothalamuses pretreated with different concentrations of HCA . They measured NPY concentrations in tissue and medium samples and found HCA suppresses appetite by reducing levels of basal neuropeptide Y (NPY), a compound that stimulates energy intake.

For another novel approach, Fabuless™, from DSM Food Specialties, is a patent-protected combination of oat and palm oils (both naturally occurring dietary lipids) that attacks appetite via the ileal brake mechanism—halting the flow of a meal through the intestines via fats that digest slowly and reach further in the gastrointestinal (GI) tract. This slowed digestion of fat triggers fullness signals and results in reduced ingestion of subsequent meals.

The ingredient underwent a few published trials conducted by the University of Ulster, Coleraine, Ireland, on satiety under its previous brand name of Olibra®. In 2000, the research team ran two double blind, placebo-controlled, within-subject crossover studies three months apart.¹⁶ The first trial involved 15 women and 14 men, and the other trial had 16 women and 14 men. In each trial, subjects were randomly given either 200 g intervention yogurt (5 g Fabuless and 1 g milk fat) or control yogurt (6 g milk fat). Four hours post-consumption, subjects were given ad libitum (open) access to a range of foods. Results showed mean energy intakes were significantly lower after the test yogurt compared with the control yogurt in both studies; similarly significant reductions were recorded for fat, protein and carbohydrate intakes in both studies. Researchers concluded small amounts of fat, especially as Fabuless, affect short-term satiety.

A similar design was used by this research team in 2001 on 20 healthy, 20 overweight and 20 obese men and women.¹⁷ Healthy and overweight subjects taking the 200 g yogurt with Fabuless had lower energy intakes at four hours post-consumption, compared to those taking control yogurt; macronutrient intakes were also significantly reduced in non-overweight and overweight subjects at four hours and in all subjects at eight hours. In 2002, the team applied a similar design to 20 male and 30 female Ulster students, who were given yogurt with 15 g fat with either 0, 2, 4 or 6 g Fabuless.¹⁸ Four hours later, they were given open access to a range of foods. Mean energy, fat, protein and carb intakes were progressively reduced with increasing doses of Fabuless in the total group, compared to control group. Energy and macronutrient intakes for the remainder of each study day and over the following 24 hours were significantly lower after all doses. Researchers concluded Fabuless reduced the effect of overeating during an ad libitum lunch meal and subsequent food intake up to 36 hours post-consumption.

Most recently, Fabuless reduced appetite and weight gain after dieting in a placebo-controlled, double blind study, conducted through the University of Maastricht.¹⁹ Fifty overweight females (aged 18 to 55) underwent a six-week weight-loss period, followed by 18 weeks of weight maintenance, during which they consumed yogurt containing either Fabuless or placebo. Subjects were weighed and measured according to height, BMI, waist and hip circumference. Those who consumed Fabuless showed no significant re-gain in body weight after six weeks of dieting and maintain consistent BMI and waist circumference, compared to placebo. Women taking Fabuless also rated their hunger levels positively, noting significantly less appetites.

Succulence

In the realm of hunger, “succulence” usually means the dangerous adjectives tasty and juicy, but in the realm of natural products the homonym “succulents” can have the opposite, but beneficial, effect. From the subfamily of succulents (cactus-like plants) come Caralluma fimbriata and Hoodia gordonii, each with storied traditions as appetite suppressants. Research has slowly been trying to catch up the intense popularity these ingredients have realized in the weight management market, but the results are showing positive potential.

During the Second World Congress for Therapies Against Obesity, Paris, 2007, Gencor Pacific presented a study on its Caralluma compound, Slimaluma, which showed fat loss and appetite suppressant activity. The Bharatidasan University, India, trial followed in vitro research showing Slimaluma inhibits progression of pre-adipocytes to adipocytes, thereby reducing formation of new fat cells and adipose tissue.

Another Indian trial, this one from St John’s National Academy of Health Sciences, Bangalore, assessed Slimaluma extract in overweight subjects in a randomized, placebo-controlled design.²⁰ Fifty adult men and women 25 to 60 years with a BMI greater than 25 were randomly assigned to receive either 1 g/d Slimaluma or placebo for 60 days. Blood glucose and lipids were tested, anthropometric measurements taken, and dietary intakes and appetites were assessed at 30 and 60 days of intervention. Results revealed waist circumference and hunger levels over the observation period significantly declined in the Slimaluma group, compared to placebo. The researchers reported the glycosides in Caralluma fimbriata may inhibit the hunger sensory mechanism of the hypothalamus.

Glycosides are also the focus in hoodia research. Researchers at Brown University Medical School, Providence, R.I., reported a specific steroidal glycoside (dubbed P57) extracted from hoodia helps decrease food intake by as much as 40 percent by increasing adenosine triphosphate (ATP) in the hypothalamus.²¹ However, this study involved injections of P57 in to rat brains, leaving open the debate on if oral P57 would penetrate the brain and affect appetite. In 2007, South African researchers identified extracts from two hoodia species, Hoodia pilifera and Hoodia gordonii, and found glycosides from these extracts have appetite suppressing properties.²² Comparing one of these glycosides to a control compound, they discovered a reduction in food intake by the Hoodia compound, which also resulted in a concomitant overall decrease in body weight; the control compound (flenfluramine, one part of Fen-Phen) produced a small decrease in food intake, but an increase in body weight.

Clearly, appetite suppression and satiety stimulation are emerging areas of science. However, in accordance with the current knowledge base on the biochemistry and mechanics of hunger and fullness, natural products that help regulate various hormones involved in signaling the brain, namely the hypothalamus, on digestive matters show great potential to positively affect when to eat, how much to consume and when to put the fork down.

REFERENCES

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