Weight Loss Gut Check

Historically, I have been rather less than sanguine about wonder drugs for weight loss, with I think quite good reason. The most promising of them to come along in years, rimonabant, was encumbered by the grisly proclivity to propagate suicide. Such is the primacy of the law of unintended consequences when we muck around with neurobiology.

Of course, we may choose to muck around less forcefully. The result of that tends to be vexing but less appalling side effects, at the cost of less therapeutic effect. So we might brand the enterprise a “damned if you do, damned if you don’t” affair. And we might not be surprised that efforts to treat normal, human metabolic tendencies- i.e., the conversion of surplus food energy into the rainy day storage depot we call fat- as a malady, might go badly awry.

In this context, then, I am somewhat surprised to note provisional interest in the latest weight-loss-by-pharmacotherapy research. Two somewhat intriguing formulations are in the research pipeline.

The first of these is a drug called fexaramine, already generating titillation in media coverage clearly intended for humans, despite testing only in mice. In the world of weight loss, that cart and those routinely trade places, so we can just move on.

The study, reported in Nature Medicine, suggests that the drug induces a feeling of fullness (I’m not exactly sure how they interviewed the mice about that…), reducing total eating; and confers a variety of metabolic benefits into the bargain. It also causes some white fat to convert to brown, the variety that boosts metabolism and burns calories. The drug does all this by mimicking a native body compound, and activating a receptor on cells in the intestinal lining.

The second of these “drugs,” generating its own media buzz, is really a combination of two nutrients: the short chain fatty acid, proprionate, bound to the fiber inulin. The fusion of the two delivers proprionate to the colon, preventing metabolism further upstream. The results of studies in mice had been encouraging, suggesting weight control benefit. The new study, reported in Gut, showed the same in overweight humans. The metabolism of proprionate in the colon induced the release of hormones signaling fullness, prevented weight gain, reduced abdominal and liver fat accumulation, and had favorable effects on insulin sensitivity.

This is all genuinely intriguing if still far from ready, at this point, for prime time. I especially like the fact that both compounds work only in the gut (although we’ve had disappointments in that neighborhood before), eliminating or much reducing the likelihood of systemic side effects. I am also encouraged that both compounds work with, rather than against, native metabolic pathways in fairly “natural” ways.

But my enthusiasm has limits despite the early good news. Or, stated differently, there’s an inevitable gut check associated with these gut-directed drugs, whatever their promise, and it’s a fairly obvious one: food is about more than weight.

Food is the fuel of the extraordinary human machine. It is the fuel for that machine in all the particulars of its diverse function, not just the regulation of weight. It is fuel for heart and nerve and sinew. It is fuel for the immune system, and the endocrine system.

And it is even more than that for our children: it is the construction material for their growing bodies. The growing body of a child is built from the deconstructed and then reconstructed components of food, and nothing else.

High performance bodies warrant high performance fuel. We are, I trust, disinclined to construct anything we care about- least of all the children we love- out of junk.

Food is about a whole lot more than what we wind up weighing.

And so it comes to this: if we eat well, we are unlikely to need a drug for weight control, whether it is a better drug or a worse one. And if we don’t eat well, a drug may or may not help with weight, but it can’t possibly substitute for the myriad other influences of diet quality.

Some people are unusually prone to weight gain, or resistant to weight loss. But for the most part, legions of us can control our weight by eating well and being active, without any drugs or medicinal formulations. Those same practices, suitable for children and octogenarians alike, don’t just help us lose weight- they help us find, and optimize health, too. There is no reason to hope any drug or compound in the pipeline can do that.

True, weight loss itself can be health enhancing. So it is that there can be a place for effective drugs, just as there is for bariatric surgery. But an excessive enthusiasm for and reliance on advances in weight loss born of laboratories rather than living rooms obscures many fundamentals. It is possible to be thin, and yet not be vital. Vitality is the real prize. We have rampant childhood obesity; will our kids take these drugs along with us? If satiety in a pill causes people to be less thoughtful about the composition of our diets, we could even suffer net harm.

The best way to control calories in the service of controlling weight is by eating better foods. Why? First, because better food matters far beyond effects on weight. Second, because one of the many virtues of wholesome foods is that they reduce the calories it takes to feel full.

The hyper-processed foods that prevail in the typical American diet do just the opposite- maximizing the calories it takes to feel full-and by design. As told by Michael Moss recently, and others before, these foods are engineered to produce overconsumption and attendant profit, largely at the expense of personal and public health.

Perhaps clever advances in pharmacotherapy can blunt that effect. But there is nothing in any pill or capsule that can substitute for the benefits of wholesome foods in sensible combinations. The pill is not an invitation to neglect healthful diet and lifestyle, and in the context of a healthful diet and lifestyle, the pill is apt to be mostly, if not entirely, superfluous.

So while drugs working in the gut to help foster satiety may prove somewhat helpful with weight control, there is more that matters about diet quality than a bathroom scale can possibly measure. That, then, is the gut check attached to these otherwise intriguing advances.

-fin

David L. Katz, MD, MPH, FACPM, FACP

Director, Yale University Prevention Research Center; Griffin Hospital
President, American College of Lifestyle Medicine
Editor-in-Chief, Childhood Obesity

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