Harry Preuss, MD, MACN, CNS, is professor of physiology, medicine and pathology at Georgetown University Medical Center in Washington, DC. He is past member of three NIH councils; author of more than 600 medical publications; and co-author of the new book, The Fat Loss Pharmacy (Broadway Books, 2007). He takes our questions on ingredients for weight management

Fi: A core concept of The Fat Loss Pharmacy is that 'weight loss' is not the concept people are looking for, it's really 'fat loss.' The metabolic goal is to reduce fat.

HP: The three biggest problems ailing the ageing demographic are that most people want to lose fat, gain muscle and increase bone-mass density. The idea is to lose weight but not muscle because muscle is the ultimate calorie burner. However, when individuals work out and take supplements to increase muscle mass, they want to lose weight, or in this case fat, but they will be disappointed with the scales unless they pay attention to their belt size or clothing size. This is one of the messages I try to get across.

I did a study on African-American women taking chromium, specifically looking at body composition and weight loss for a control group and a chromium group. The chromium group didn't lose much weight during the few months of the study. But when we looked at fat vs muscle loss, the women in the placebo group lost 60 per cent of that weight as muscle protein, which was alarming, but when we added chromium it was only 10 per cent. So right then and there, I said 'anyone on caloric-restricted diets or appetite suppressors should be on something like chromium.'

Fi: Why chromium?

HP: It probably works because of its influence on the insulin system. Basically, if one has a disturbed insulin system, the tendency is to lose muscle and gain fat. As one gets older, it is common to become more insulin resistant. Associated with that is the tendency to lose muscle mass and to gain fat, usually around the middle. Part of our goal is to reverse this frustrating and health-damaging progression of events common in ageing.

The other benefit is, the rats I supply with chromium live 20 per cent longer. The chromium not only keeps the muscle on and the fat off, it may help in a number of other bodily systems that lead to longevity.

Fi: It's said you need a minimum of two studies with consumer-relevant benefits to launch and market a product. How do you feel about that?

HP: The first goal is for a compound to be safe. And then it has to be effective. If an ingredient has some risk associated with it, it better be darned effective to even consider putting it on the market.

An example is ephedra, perhaps the best weight-loss substance out there. But we couldn't get rational people in one room to talk about the benefits and risks. We accept that Tylenol causes a lot of deaths, but the benefits are so great that it's still marketed. Dietary supplements don't get the same consideration from certain sectors of the health industry, which seems unfair; after all, over-consumption of something as benign as water can kill a person.

After safety, then one has to show a benefit. I'd love to see more research. But these poor guys out there in the natural-supplements field have difficulty getting patents on products, and the minute we do research our competitors grab it and run with it. If there was some way for people to do the research and get a financial benefit for a defined length of time, they'd be more apt to put the money into research. But there is a wait-and-see attitude for the other guy to do the work first, and then the copycats jump on their coat tails.

If something seems to work, it is essential to find a good supplier, one that you can trust — look at the hoodia market, you don't know what you're getting half the time. Another example is HCA compounds, the totally calcium-type are poorly absorbed. There is a checklist: find the correct product; make sure it's product the supplier is claiming and at the right dose, and then, if it is a weight-loss study, pay attention to fat loss and muscle mass. Lastly, for optimal success, the study subjects must comply.

Fi: EGCG, the primary catechin in green tea, seems to burn more calories, in particular with caffeine.

HP: Some claim it works on the fat, specifically releasing fat from storage. Most go with the notion that it increases metabolism by burning more calories. There are claims that it burns 80-90cal/day more. Caffeine is an important component to get a maximum effect, just as with ephedra. Of course, increased caffeine also increases the probability of negative side effects. In one study, researchers tried to increase the dose of caffeine to make it more effective, but 90mg EGCG and 50mg caffeine was as effective as going with higher doses.

Fi: Is caffeine better in combination, or can it work alone just fine?

HP: You could use caffeine alone. But there are so many arguments about caffeine that are not settled. It can raise blood pressure, but it comes back to normal after a while just like ephedra. Caffeine causes sleeping problems and can cause arrhythmias in persons with a history of irregular heartbeats. It's a good weight-loss compound, but until there is more information, it has limitations.

Fi: CLA also seems to work on fat.

HP: In 1997, Michael Pariza's laboratory at the Food Research Institute at the University of Wisconsin, Madison, showed that mice fed a diet supplemented with CLA ended up with 60 per cent less body fat and 14 per cent more lean body mass than mice not fed CLA. In that same study, cellular analysis showed that CLA might stop fat from being deposited in fat cells, that it could help break down fat cells, and that it may help burn up fatty acids in both fat cells and muscle cells.

Fi: Why do some studies show that CLA doesn't work?

HP: I question, did the researchers use the right prep, the right dose and the right timing? Did they check fat and muscle composition? It is common for some exercise-study participants to actually gain weight, which is not always a marker of failure. And, again, compliance is very important. All these things can mean the difference between a successful study and a mediocre study.

Then there is the way in which the study is evaluated. For instance, the FDA wants you to use intention to treat analysis — say you start out with 40 patients in control, 40 in treatment. The study is to go two months, but maybe five drop out in each group at two weeks and five drop out at four weeks. FDA wants you to include those dropouts in the data. It doesn't affect the placebo group, but it mucks up the data in the treatment group. That's a set-up to get negative results.

Fi: You've done research on HCA, which appears to lower the level of a key enzyme that helps sugars and starches turn into fat. Explain this mechanism.

HP: Carbohydrates are metabolised into two-carbon chains, then the two-carbon chain is converted into fat. Hydroxycitric acid, HCA, prevents the formation of two-carbon chains so the precursor that builds up fat is prevented. HCA has two major effects that are well known — appetite suppression and blocking carbohydrates from turning into fats.

Fi: Is that at all similar to the way carb blockers work?

HP: With carb blockers, there is a deprivation of carb calories. It works because of so-called resistant starches, which are basically starches that one digests right away, go distally into the intestines and are fermented. With carb blockers, in a sense you're doing that already — you're preventing absorption of absorbable carbohydrates. When rats in our lab were fed carb blockers, blood pressure came down, they were thinner, a little leaner, and had healthier cholesterol levels.

Starch blockers are now being baked right into food. This could well be the future. I love spaghetti. I'd love to find a noodle that tastes the same but has starch blockers. In my mind, if it's possible, it's definitely a good thing.

Fi: Is chitosan different from other soluble fibres? Or are all soluble fibres the same?

HP: Chitosan can work like others fibres because it is filling, and satiety slows absorption. But also because of charge and solubility, chitosan specifically grabs onto fats and can keep fats in place so the body doesn't absorb them. Chitosan, from crushed sea shells, is used to pick up oil spills in the ocean. It is the same concept for the body that once in the gut, chitosan collects and absorbs fat.

Fi: Why advocate muscle builders in a weight programme? What's the story with the branched-chain amino acids (BCAAs)?

HP: As one gets older, there is a tendency to accumulate fat and lose muscle. The problem is muscle is a calorie burner that'll help keep the fat off. At the same time, muscle loss causes frailty, which can lead to falls, especially for elderly women. Bone loss is common, which is why there are so many little old bent-over women walking around, but muscle loss also contributes to falls.

Fi: Herbal appetite suppressants are intriguing, especially when accompanied by stories of locals — African bushmen eating hoodia or the 'famine food' of India, caralluma. Do hoodia and caralluma work similarly?

HP: It's the same story, but there are a few different major compounds within them that are believed to do the work. Hoodia could be a good compound, but there are no clinicals on hoodia, so there is not much more I can say about it.

Caralluma has one or two studies, which is more than hoodia, but the herb lacks good publicity. I've spoken with manufacturers about hoodia and caralluma, the problem for both is the cost. Researchers haven't found a way to cultivate either herb in a large enough quantity to serve the world, which is why it is expensive.

Fi: You've conducted research on chromium, HCA, Gymnema sylvestre. What are your current research interests?

HP: I just reported one at Expo West, looking at maitake mushroom fraction SX, an insulin sensitiser. It has properties similar to chromium. The most interesting find is that it works on the renin angiotensin system. Renin is a substance made and released by the kidney that makes angiotensin. This process requires the aid of a lung enzyme to create angiotensin II, which is a vasoconstrictor — in other words, angiotensin II causes high blood pressure.

The pharmaceutical industry introduced ACE inhibitors, which block production of antiogensun II and therefore lower blood pressure. Recent evidence shows that other than vasoconstricting and causing elevations in blood pressure, angiotensin II contributes to atherosclerosis by releasing inflammatory, pro-oxidant cytokines. Our research shows that both the niacin-bound chromium and maitake fraction SX inhibits the conversion enzyme, which makes them ACE inhibitors similar to prescription drugs, but safer.

We are also working on metabolic syndrome including weight gain and the cardiovascular system, which are tied together with metabolic syndrome and fat mass. I expect further research in this arena, if the company can generate the funds.

Fi: If you were to advise a manufacturer to bundle some of these ingredients for the greatest benefit for the greatest number, which ingredients would you advise to include in a formula? Would you cover all the bases — fat busters, insulin regulators, carb inhibitors, appetite suppressors, muscle builders?

HP: One sharp company made their fat-loss pill based on ingredients in the first five chapters of my book. Personally, I've been intrigued by combining appetite suppressants like HCA with caralluma. Supposedly, we think they suppress appetite via different mechanisms so they could be better than either alone. I'd like to do studies to find out if my assumptions are true. Carb blockers work with heavy-carb meals to block starch absorption, while L-arabinose blocks sugar absorption. If a meal is high in fat, I might use fibres such as chitosan in it.

These ideas are ancillary to other research. I prefer to work with appetite suppressants that work on the insulin system. The goal is to drive weight loss toward fat loss, rather than muscle. The way to do this is to add an insulin sensitiser like maitake SX, chromium or cinnamon. Still, there's no perfect formula right now, which is why the latest book includes how each individual ingredient works.