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Tue, Jun-01-04, 19:03

CCK: More to Appetite Than Glycemic Whims

By: Ralph Ofcarcik, Ph.D.
Director of Nutrition Services

According to the pro-vegan experts of 80’s, the simple solution to overeating was to fill up your stomach with foods containing more volume per calorie, i.e. low-energy dense foods. Thus, meals prepared from ingredients containing natural calorie-free bulking agents (fibers) became the smart choice for weight-conscious consumers who liked to eat (a lot). Later, Barry Sears formally introduced the concept of reactive hypoglycemia by including a modified version of the Glycemic Index in the Appendix of The Zone, published in 1995. At the time, Dr. Sears advised us to avoid those foods which, under fasting conditions, caused rapid spikes and subsequent dips in blood sugar (resulting in fatigue, irritability, and hunger). The concept of avoiding high-glycemic foods, like sugar, rice cakes, potatoes, white bread, etc., was the basis of Sugar Busters (“never eat anything white”), published three years later in 1998. Now, amid the current carb-loathing frenzy, high-glycemic foods (like potatoes) are passionately avoided and touted as our worst dietary nightmares. Simple answers, however, have never been the norm for characterizing manageable aspects of human physiology. Appetite control, for instance, is far more complex than insulin/glycemia issues or energy-density control.

Consider CCK.

Cholecystokinin (CCK) is a small proteinaceous hormone that is released into the blood after food intake by endocrine cells lining the small intestine. Ultimately, the downstream signal to the hypothalamus from the CCK serum spike is to STOP EATING-I FEEL FULL! In between the hypothalamus stimulus and the food-induced rise in blood CCK, other appetite-suppressing events take place: slowing down of gastric emptying (the vegans were partially right: a full tummy = a full feeling), activation of the gastric vagus nerve (which sends a full message to the appetite-control center of the hypothalamus), and binding of the hormone to receptor sites in the central nervous system involved in satiety. CCK also contributes to the catabolism (breakdown) of protein and fat by signaling the release of pancreatic juices and bile (gallbladder). The resulting peptides, amino acids, glycerides, and fatty acids are suspected to cause an additional release of CCK. The ability of cholecystokinin to suppress appetite makes it a potential useful tool for the treatment of obesity – agreed?

A Brief History
Just prior to WWII, researchers determined that an extract prepared from the walls of the small intestine contracted the gallbladder, causing a release of bile. The substance was logically named “cholecystokinin” (that which excites the gallbladder). Thirty years later, a hormone dubbed “pancreozymin” (known to cause the release of pancreatic digestive enzymes) was found to be the same exact same peptide as bile-producing CCK. Because of this and other discoveries in the early 60’s, CCK became a popular subject of conversation (and research) in biochemical and medical circles - its importance in the digestive process now better understood.

During the next two decades (approx 1960-1980), a few animal studies demonstrated CCK’s pronounced effect on appetite. Antin et al1 demonstrated that rats given CCK injections had an immediate suppression in their appetite over the next half hour. Later, Della-Fera and Baile2 reported an increase in appetite when sheep or rats were injected with a CCK receptor blocker. Up until this time, researchers suspected a role of CCK in appetite suppression with limited knowledge of its etiology. The Della-Fera/Baile project, without doubt, was a major breakthrough in CCK research, convincing everyone of the peptide’s hunger-suppressing role as a physiological modulator, not a metabolic agent.

The 1980’s saw the first human research testing CCK as an appetite suppressant. In 1980, Kissileff et al3 reported that intravenous infusions of CCK, administered to adult volunteers, reduced food intake by approximately 20%. CCK was reported to work by inducing satiety soon after the start of food consumption – without nausea or other side effects. In 1982, Stacher et al4 demonstrated a 17% inhibition of food intake on volunteers given a CCK infusion. Still later, Hill et al5 demonstrated that the oral administration of a protease inhibitor in potatoes (previously shown to stimulate CCK release) rendered a statistically significant 20% decrease in food intake (compared to a control group). Over the past 2 years, numerous studies have been undertaken in an attempt to determine how to maximize CCK release by diet.

Dietary Factors that Increase CCK Release
To date, the following food components have been reported to maximize CCK release:

• Protein
• Fat
• Potato extract (containing Pot II – a CCK-stimulating protein)
• Soluble fiber (guar gum, glucomannan)

Predictably, all research focused on CCK release has been conducted in support of supplement and pharmaceutical development involving trials on food components (protein, fiber, fat), but not whole foods. Realistically, it’s difficult, even unintelligent, to postulate whether eating high-glycemic whole potatoes will provide the same overall calorie-suppression benefit as consuming a supplement containing only concentrated macronutrients – a judgment-call situation heavily entrenched in the grey area. And, there are supplements, like Satietrol (from Pacific Health Laboratories, Inc.), which contain a unique blend of food ingredients (like glycomacropeptide - a milk protein, guar gum, glucomannan, and potato fiber extract) and are backed by published studies of appetite suppression (and weight loss). But the question remains: WILL EATING POTATOES RESULT IN FEWER CALORIES CONSUMED DESPITE ITS HIGH-GLYCEMIC EFFECT?

CCK-Satiety Index Connection
Whether eating whole foods containing CCK stimulators is helpful in curbing hunger may be less than pure speculation if we consider the work of Suzanne Holt, Ph.D. and professor of biochemistry at the University of Sydney in Australia. For the past 20 years, Dr. Holt and her associates have been attempting to determine which foods, calorie per calorie, quell the appetite for the longest period of time. Called the Satiety Index6, it was developed by having fasting student volunteers consume 240-calorie portions of a test food. They then rated their feelings of hunger every 15 minutes for 2 hours. At the end of two hours, they were allowed to each as much as they wanted from a buffet – all under the watchful eyes of the researchers. Using a formula developed from the subjective evaluations of hunger and the amount of food consumed after two hours, a rating system was developed in which foods were ranked, low-satiety to high satiety, Using white bread as the standard (S.I. = 100), Holt scored 38 foods. Foods scoring higher than 100 were judged to be more satisfying than white bread, while those under 100 were less satisfying. Foods that have a higher satiety index keep hunger down longer, and would be better choices for those who want to lose weight. Interestingly, the highest-rated appetite-suppressing foods also contained components shown to influence CCK release as indicated in the following chart:

Highest Ranking Satiety Inducing Foods

Food Satiety Value CCK Inference
Potatoes 323% Contains Pot-II protein, shown to stimulate CCK release
Fish 225% High in protein, shown to stimulate CCK release
Oatmeal 209% High in soluble fiber, shown to stimulate CCK release
Oranges 202% High in pectin, shown to stimulate CCK release
Apples 197% High in pectin, shown to stimulate CCK release
Brown Pasta
188% High in soluble fiber, shown to stimulate CCK release
Beef 176% High in protein, shown to stimulate CCK release
Baked Beans 168% High in soluble fiber, shown to stimulate CCK release
Grapes 162% High in pectin, shown to stimulate CCK release
Whole-Grain Bread 157% High in soluble fiber, shown to stimulate CCK release

Interesting, eh? Although far from conclusive, it appears that Holt’s greatest hunger-suppressing foods are also lucrative sources of CCK stimulators. Holt’s Satiety Index entries that demonstrated little or no control over hunger were, generally, high-carb, low-fiber, low-protein foods (like baked goods containing fiberless white flour) – foods tested high in glycemic response that, in addition, would be suspected poor CCK stimulators.

Will what we have seen so far support any dietary regime? Not by a long shot. Tons of supportive studies will be needed before we can responsibly advocate a diet based upon CCK stimulation and subsequent food intake. During the interim (next 5-20 years), consider a moderate diet consisting of leaner meats (protein stimulus of CCK), healthy oils (fatty acid stimulus of CCK), and soluble fiber (whole grains – especially oats, legumes, apples, oranges – all CCK-stimulators). Avoid high-glycemic foods, except potatoes - the current CCK stimulating champion. Unless you are diabetic, enjoy the world’s most popular tuber without glycemic guilt - but take it easy with the butter and sour cream.

1. Cholecystokinin elicits the complete behavioral sequence of satiety in rats. Antin J; Gibbs J; Holt J; Young RC; Smith GP J Comp Physiol Psychol, 1975 Sep, 89:7, 784-90

2. Cholecystokinin octapeptide: continuous picomole injections into the cerebral ventricles of sheep suppress feeding. Della-Fera MA; Baile CA Science (United States), Oct 26 1979, 206(4417) p471-3

3. C-terminal octapeptide of cholecystokinin decreases food intake in man. Kissileff HR; Pi Sunyer FX; Thornton J; Smith GP Am J Clin Nutr, 1981 Feb, 34:2, 154-60

4. Cholecystokinin octapeptide decreases intake of solid food in man. Stacher G; Steinringer H; Schmierer G; Schneider C; Winklehner S Peptides, 1982 Mar, 3:2, 133-6

5. Oral administration of proteinase inhibitor II from potatoes reduces energy intake in man. Hill AJ; Peikin SR; Ryan CA; Blundell JE Physiol Behav, 1990 Aug, 48:2, 241-6

6. A satiety index of common foods. Holt SH; Miller JC; Petocz P; et al Eur J Clin Nutr (England), Sep 1995, 49(9) p675-90

Tue, Jun-01-04, 20:43
Interesting, but I would suggest that the insulin resistant population would tend to be under represented in the student volunteers used to create the satiety index, which would skew the results for the high carb/high GI foods listed such as potato. I also wonder whether a two hour test is long enough to see glucose spike/crash and the resultant carb craving in every individual.

As far as 'we' are concerned the suggestion would be to seek out high protein sources such as fish and meat and natural sources of soluable fibre - which sounds like Protein Power or Atkins to me.