From the remote Kalahari, an Age-Old Hunger Remedy
Hoodia Can Help You Eat Less
Research uncovers the role of its active ingredient, P57, in appetite suppression
By Will Block
n the 1980 film comedy The Gods Must Be Crazy, a diminutive Bushman in the Kalahari Desert is seen digging up a large tuber from beneath the seemingly featureless sand. Using a sharpened piece of wood, he carefully scrapes a handful of moist pulp from the tuber, wads it into a loose ball, and holds it above his head. Then he slowly squeezes out the water, using his downturned thumb to guide the precious drops toward his open mouth. Quite a neat trick if you’re ever lost in the desert without a canteen.
Ah, but how did the Bushman know where to dig for that life-sustaining tuber? That’s a mystery, but why he dug is not. Not only is there no running water in the Kalahari, there is no surface water at all for most of each year. Only during the brief rainy season do the Bushmen have the luxury of a water supply in the form of … water. To survive during the rest of the year, they must rely on the water content of their food, the morning dew they collect from leaves, and whatever moisture they can extract from hidden sources, such as underground tubers.
Bushmen—Masters of Survival
If extreme survival skills were an Olympic event, the Bushmen—the most ancient group of nomadic hunter-gatherers on earth, and known to anthropologists as the San—would win the gold in a breeze. They have survived in their unimaginably harsh environment for at least 27,000 years, and possibly much longer than that. Over that vast expanse of time, they learned countless survival skills, such as how to make tools from wood or stone, how to find water and food, how to avoid becoming food for predators, and how to suppress their appetite.
Say what? Yes, you read that right: how to suppress their appetite. But how could appetite suppression possibly be of benefit to skinny little people in a region where just finding enough food to eat is a never-ending challenge? The answer is that it’s not a good idea to eat while on a lengthy hunt, walking or running as much as a hundred miles in pursuit of elusive prey (and naked but for a loincloth and a bow and poisoned arrows). Carrying food from home would slow the Bushmen down, as would a full belly. And once they killed their prey, they wouldn’t eat any of it before carrying it home to share equally with everyone in the village—a long haul with a heavy load.
Hoodia Did (Was) the Trick
Needless to say, the hunters would be terribly hungry until they finally returned home for the feast—unless, during the hunt, they opened their bag of medicinal tricks and pulled out the one for appetite suppression. This trick, which allowed them to escape the relentless torment of hunger pangs, has a name: Hoodia gordonii (the great escape artist Harry Houdini might have been amused to see that his last name could be found within it).
Hoodia gordonii is the botanical name (there is no common name in English, but the Bushmen call it xhoba) for a spiny, perennial succulent found throughout southern Africa, including the immense Kalahari, which covers most of Botswana and Namibia and parts of Angola and South Africa. Although it looks like a small cactus, Hoodia is actually a type of milkweed. Being a succulent, it contains a good deal of moisture, which, although bitter tasting, is obviously useful when you’re out in the desert. Sucking on the pulpy flesh, the Bushmen could not only slake their thirst but also, as they discovered ages ago, quell their hunger. In addition, according to one contemporary Bushman, Hoodia would give them enough energy to walk all day or make love all night, and it cured a hangover or settled an upset stomach.*
The Magic Ingredient Is P57
Well, you can’t attribute all that to the water content of Hoodia, so there must be something else. Indeed, among the many chemical compounds found in the sap of Hoodia, scientists in South Africa have discovered an appetite-suppressing compound that they’ve nicknamed P57 (its real name is forbiddingly long and complicated). P57 is a steroidal glycoside, i.e., a steroid molecule chemically bonded to a sugar molecule (in this case, a chain of three sugars, actually).
Scientists at Brown University Medical School in Providence became interested in P57 as a means for investigating how the sense of satiety, or fullness, is induced in our brains, telling us to stop eating. Because P57 is an anorectic (an agent that suppresses appetite), discovering the mechanism by which it acts on the brain should shed some light on this question.
Is P57 a Cardiac Glycoside?
The researchers were intrigued by the fact that P57 is chemically similar to a class of plant-derived compounds called cardiac glycosides, of which the ones derived from various foxglove species (genus Digitalis) are the best known. These powerful drugs increase the force of contraction of the heart muscle and help maintain normal heart rate and rhythm. A common side effect of the cardiac glycosides is loss of appetite.
Like many drugs, cardiac glycosides act by interacting with specific receptor molecules embedded in the walls of our cells. When stimulated by such interactions, these receptors (which are large, complex proteins that act as molecular channels) initiate a chain of events inside the cell, the net effect of which is the action attributed to the drug. In the case of cardiac glycosides, the receptor molecule is called Na/K-ATPase. Its primary function is to regulate the flow of sodium ions (Na+) and potassium ions (K+) into and out of the cell through the molecular channel, using chemical energy provided by molecules of ATP (adenosine triphosphate). This process, called a sodium/potassium pump, is critically important in maintaining proper cell function and allowing cells to perform certain actions, such as muscle contraction (including that of the heart muscle) and nervous impulse transmission.
Despite the similarities (including the appetite-suppressing effect) between P57 and cardiac glycosides, however, initial studies with P57 failed to show any effect on Na/K-ATPase receptors, indicating that P57 is probably not a cardiac glycoside. P57 also failed to show an effect on a wide range of other types of receptors. Thus its mode of action at the cellular level was somewhat of a mystery.
P57 Makes Tough Rats Eat Less
The Brown researchers conducted a series of experiments with normal, healthy rats in which they injected minuscule amounts of P57 directly into their brains—specifically, into a small cavity called the third intracerebral ventricle, located above the hypothalamus, which lies deep in the forebrain, just above the pituitary gland.* The hypothalamus is the brain’s center for the control of certain primitive physical and emotional functions, such as sleep, mood, temperature regulation, sex drive, heart rate, and appetite. It both receives and transmits chemical signals in the form of hormones and other molecules that are involved in these processes.
The purpose of these injections was to determine whether P57’s appetite-suppressing effect is the result of its direct action on the hypothalamus—and it appears that it is. In multiple trials with the injected rats, food intake was reduced by 50–60% during the first 24 hours after the injections, and the effect, which was dose-dependent, lasted for about 24–48 hours. (I know what you’re thinking: “I might not want to eat very much right after brain surgery either.” But bear in mind that rats are incredibly tough animals, and besides, these reductions in food intake were observed in comparison with that of a group of control rats, which had also been brain-injected, albeit with an inert substance. Thus the reductions represent a genuine effect due to P57.)
Significantly, intraperitoneal (in the abdominal cavity) injections of P57 did not significantly reduce the rats’ food intake. This suggests that, for it to work, P57 must enter the bloodstream, which carries it to all parts of the body, including the hypothalamus.
P57 Increases ATP Levels in the Hypothalamus
Further experiments by the Brown researchers confirmed the lack of a direct effect of P57 on the Na/K-
ATPase receptors in hypothalamic cell cultures. On the other hand, P57 did significantly block the action of ouabain, a cardiac glycoside, on these receptors. That suggested that there was some sort of effect on the receptors’ function. The researchers ruled out a direct toxic effect, because they state that there has been no evidence of toxicity for P57, either in laboratory experiments or in animal studies. They decided to test for an effect of P57 on the intracellular concentration of ATP, the energy molecule that drives the sodium/potassium pump mentioned earlier.
What Is the Evidence?
The most compelling evidence for the safety and efficacy of Hoodia gordonii as an appetite suppressant comes from what may be, in effect, the longest-running medical experiment in human history: its use by the Bushmen of the Kalahari for probably tens of thousands of years. Who’s going to argue that they don’t know what they’re talking about, even if they don’t have Ph.D.’s in pharmacology?
Nonetheless, modern pharmacologists and physicians would like to see scientific evidence for the benefits of Hoodia, if only to learn how it works and how, perhaps, it could be made to work even better. Most of us don’t have to track prey animals in the desert for days on end, but millions of us would like to lose weight simply by eating less. So far, there have been no published clinical trials on Hoodia in peer-reviewed scientific journals, although there have been unpublished reports of its efficacy by two drug companies that have been developing it for commercial purposes.
Can Hoodia Reverse Diabetes?
As mentioned in the paper by the Brown researchers, there have been several unpublished studies with rats and humans in which homogenates or extracts of Hoodia produced substantial anorexic (appetite-suppressing) effects that lasted for the duration of the studies (up to 8 weeks). Included in these studies were experiments with obese diabetic rats, in which Hoodia was claimed to have produced a “reversal of diabetes.” Although it’s not clear to what extent this occurred (and there was no indication of the source of the information), any degree of reversal of diabetes is obviously desirable.
Another hint of such an effect came in two brief papers published a few years ago in which it was claimed that Hoodia produced “modest decreases” in blood glucose and a 15% decrease in blood glucose in both lean and obese (but nondiabetic) rats. These improvements accompanied a substantial loss of weight in the rats, owing to Hoodia’s anorexic effect. It is well known that obesity and type 2 diabetes go hand-in-hand in humans and that weight loss in obese individuals tends to reverse the symptoms of diabetes. If Hoodia can induce both weight loss and glucose reduction independently, as may be the case, so much the better.
- MacLean DB, Luo L-G. Increased ATP content/production in the hypothalamus may be a signal for energy sensing of satiety: studies of the anorectic mechanism of a plant steroidal glycoside. Brain Res 2004;
- Tulp OL, Harbi NA, Mihalov J, DerMarderosian A. Effect of Hoodia plant on food intake and body weight in lean and obese LA/Ntul//-cp rats. FASEB J 2001 Mar 7;15(4):A404.
- Tulp OL, Harbi NA, DerMarderosian A. Effect of Hoodia plant on weight loss in congenic obese LA/Ntul//-cp rats. FASEB J 2002 Mar 20;16(4):A648.
Using a hypothalamic cell culture, they found that P57 increased the concentration of ATP by about 50% following a 30-minute incubation (ouabain had no such effect). When they tested for a similar effect in live rats that were fed a normal diet, they found that brain injection with P57 increased the hypothalamic ATP levels by about 100% (i.e., a 2-fold increase) compared with controls.
The researchers then tested rats that had been on a severe hypocaloric (low-calorie) diet for 4 days. Without P57, these rats had hypothalamic ATP levels about 40% below normal (the ATP levels in their livers were about 60% below normal).* One might expect such decreases, because ATP is created in the body by the metabolism of food, so less food should result in less ATP—unless some other factor temporarily stimulates increased production of ATP. And that, apparently, is what P57 did, at least in the hypothalamus: when these underfed rats were brain-injected with P57, their hypothalamic ATP levels rose to about normal, whereas the ATP levels in the control rats remained low.
Increased ATP Is a Signal to Stop Eating
Thus, the researchers established that P57 increases ATP levels in the rat hypothalamus (but how it does that is still unknown), leading them to suggest that “… a key mechanism of hypothalamic regulation of food intake is altered intracellular concentrations of ATP.” In other words, increased ATP production is a biochemical signal for appetite suppression. The message is, “Hey! You’ve got enough ATP here, which means that you’ve had enough food—therefore, you don’t feel hungry, so stop eating.”
The authors went on to say that this demonstration of P57’s appetite-suppressing action in the central nervous system in no way precludes the possibility that it may act to suppress appetite in other ways in other parts of the body as well, e.g., through effects on the peripheral nervous system, on the stomach, or on potentially appetite-suppressing hormones, such as CCK (cholecystokinin).†
A Gift from the Past
With obesity (and just plain overweight) having become a major public health problem in our society, it behooves all of us to watch our weight and not let it climb to a level that could seriously impair our health and our prospects for a long life. The best and simplest way to lose weight is to eat less (easier said than done, of course), and one way to eat less is to suppress your appetite—a great option when you think about it. After all, which would you rather do—eat less because you feel you must, or eat less because you’re less hungry?
How fortunate we are to be the modern beneficiaries of a time-tested remedy for hunger pangs that comes to us from the remarkable Bushmen, who have used it since long before the dawn of recorded history, in a place that has tested to the utmost degree the ability of the human species to survive against the odds.
- Thompson G. Bushmen squeeze money from a humble cactus. The New York Times, April 1, 2003.
- MacLean DB, Luo L-G. Increased ATP content/production in the hypothalamus may be a signal for energy sensing of satiety: studies of the anorectic mechanism of a plant steroidal glycoside. Brain Res 2004;1020:1-11.
Will Block is the publisher and editorial director of Life Enhancement magazine.