Leptin and Lectins: Part II

Why do Americans become overweight and diseased on a high-carbohydrate diet while the carbohydrate-loving Kuna and Kitavans remain exceptionally free of chronic disease? Dr. Lindeberg proposes an answer- grains.

Dr. Lindeberg's hypothesis is that grains cause leptin resistance, which as we saw in the last post, has the potential to precipitate the metabolic syndrome and its various consorts. It's an attractive idea. The Kitavans (who he has studied personally), Kuna, and other cultures in Melanesia, Malaysia, Africa, the Arctic and South America, do not suffer from the diseases of civilization. These are all cultures that consume little or no grain, despite some having starchy diets. The Kitavans have low circulating leptin and remain lean and disease-free despite a high intake of carbohydrate.

Dr. Lindeberg says that grain-based cultures almost universally suffer from varying degrees of our illnesses, although his references to support that statement are unsatisfying. He did provide a reference showing that stroke occurs in affluent grain-based societies (whereas it seems not to in Kitavans), but I would really have liked to see a side-by-side comparison of cultures with similar lifestyles and differing grain intakes.

One thing that's certain is humans have not been eating grains for very long. Before the invention of agriculture in the fertile crescent, grains were a minor and seasonal crop for a small number of groups. Something we have been eating for a long time however is starchy tubers, bulbs and roots. Hunter-gatherers didn't generally go after wild grass seeds (grains) because they weren't a concentrated enough food source in most places. If you collect grass seeds all day, you might end up with a mouthful, after which you have to soak, grind, and cook them before chowing down. Dig up a few camas bulbs however, and you've got yourself a meal in 5 minutes.

The distinction between different sources of starch may lie in a class of molecules called lectins. Lectins were originally defined by their ability to aggregate red blood cells (erythrocytes). They do this by binding to the natural coating of carbohydrate on the cells' surface. A more current definition of a lectin is a molecule that specifically binds carbohydrate. Lectins are found throughout all kingdoms of life, and they serve a variety of useful functions. Many plants use lectins as a defense against hungry animals. Thus, an animal that is not adapted to the lectins in the plant it's eating may suffer damage or death.

Grains and legumes (beans, soy, peas, peanuts) are rich in some particularly nasty lectins. Especially wheat. Some can degrade the intestinal lining. Some have the ability to pass through the intestinal lining and show up in the bloodstream. Once in the bloodstream, they may bind all sorts of carbohydrate-containing proteins in the body, including the insulin receptor. They could theoretically bind the leptin receptor, which also contains carbohydrate (= it's glycosylated), potentially desensitizing it. This remains to be tested, and to my knowledge is pure speculation at this point. What is not so speculative is that once you're leptin-resistant, you become obese and insulin resistant, and at that point you are intolerant to any type of carbohydrate. This may explain the efficacy of carbohydrate restriction in weight loss and improving general health.

Another thing I have to mention about lectins is they can be broken down by certain food processing techniques. Remember all those old-fashioned things our grandparents used to do to grains and beans before eating them, like soaking beans overnight, sourdough-fermenting bread dough and nixtamalizing corn? All those things we've abandoned in favor of modern convenience foods? You guessed it, those reduce lectins dramatically, along with a long list of other toxins like phytic acid and protease inhibitors. Modern yeast-leavened breads, pastries, crackers, corn and soy products are no longer prepared according to these methods, and their lectin levels are typically much higher. One thing to keep in mind is that these processes reduce but generally do not eliminate lectins and other toxins.

The thing I really like about Dr. Lindeberg's idea is it explains a lot of what is happening in the world around us. The Kitavans eat yams, sweet potatoes, taro and tapioca as their staples. Incidentally, the long-lived Okinawans also eat sweet potatoes as a staple. The Kuna eat mostly plantains, yucca and kidney beans. These are three exceptionally healthy populations with a very low intake of grains. What happens when you feed these same people wheat? The Kuna have a well-documented rise in blood pressure, diabetes and cardiovascular disease mortality when they move to an urban, westernized setting. Okinawans became obese and unhealthy when American food was introduced. Wherever white flour and sugar go, the diseases of civilization follow. Weston Price documented this in the dental and skeletal health of 14 different cultures throughout the world.

It also explains what's going on under our very noses. Like I mentioned earlier, modern processed food is rich in lectins because it hasn't been treated by soaking, sprouting or bacterial fermentation. Soy has one of the highest lectin activities of any food, unless it's traditionally fermented into miso, tempeh, tamari or natto. As we've begun relying more and more on industrial food, our health has taken a major turn for the worse. Obesity is soaring in the US and diabetes is close on its heels.

I think it's very likely that grains are one of the major culprits in the diseases of civilization. This could be due to lectins causing leptin resistance. It's a fantastic hypothesis that could explain the health problems we see in modern grain-based societies.

Leptin and Lectins

I've been puzzled by an interesting question lately. Why is it that certain cultures are able to eat large amounts of carbohydrate and remain healthy, while others suffer from overweight and disease? How do the pre-industrial Kuna and Kitavans maintain their insulin sensitivity while their bodies are being bombarded by an amount of carbohydrate that makes the average American look like a bowling ball?

I read a very interesting post on the Modern Forager yesterday that sent me on a nerd safari through the scientific literature. The paper that inspired the Modern Forager post is a review by Dr. Staffan Lindeberg. In it, he attempts to draw a link between compounds called lectins, found in grains (among other things), and resistance to the hormone leptin. Let's take a step back and go over some background.

One of the most-studied animal models of obesity is called the "Zucker" rat. This rat has a missense mutation in its leptin receptor gene, causing it to be nonfunctional. Leptin is a hormone that signals satiety, or fullness. It's secreted by fat tissue. The more fat tissue an animal has, the more leptin it secretes. Normally, this creates negative feedback that causes it to eat less when fat begins to accumulate, keeping its weight within a narrow range.

Zucker rats secrete leptin just fine, but they lack leptin receptors in their brain. Their blood leptin is high but their brain isn't listening. Thus, the signal to stop eating never gets through and they eat themselves to morbid obesity. Cardiovascular disease and diabetes follow shortly thereafter, unless you remove their visceral fat surgically.

The reason Zucker rats are so interesting is they faithfully reproduce so many features of the disease of civilization in humans. They become obese, hypometabolic, develop insulin resistance, impaired glucose tolerance, dyslipidemia, diabetes, and cardiovascular disease. Basically, severe metabolic syndrome. So here's a rat that shows that leptin resistance can cause something that looks a whole heck of a lot like the disease of civilization in humans.

For this model to be relevant to us, we'd expect that humans with metabolic syndrome should be leptin-resistant. Well what do you know, administering leptin to obese people doesn't cause satiety like it does in thin people. Furthermore, elevated leptin predicts the onset of obesity and metabolic syndrome. It also predicts insulin resistance. Yes, you read that right, leptin resistance comes before insulin resistance.

Interestingly enough, the carbohydrate-loving Kitavans don't get elevated leptin like europeans do, and they don't become overweight, develop insulin dysfunction or the metabolic syndrome either. This all suggests that leptin may be the keystone in the whole disease process, but what accounts for the differences in leptin levels between populations?

I'll talk about a possible explanation in my next post.

Say Hello to the Kuna

For those of you who haven't been reading the comments, we've been having a spirited discussion about the diet and health of hunter-gatherers here. I brought up the Kuna indians in Panama, who are immune to hypertension, live a good long time, do not gain excess weight, and seem to have less cardiovascular disease and cancer than their city-dwelling cousins.

I was hungry for more information about the Kuna lifestyle, so over the last few days, I've dug up every paper I could find on them. The first paper describing their lack of hypertension was published in 1944 and I don't have access to the full text. In 1997, a series of studies began, headed by Dr. Norman Hollenberg at Harvard. He confirmed the blood pressure findings, and collected data on their diet, lifestyle and kidney function. Here's a summary:

The Kuna are half hunter-gatherers, half agricultural. They cultivate plantains, corn, cocoa, yucca, kidney beans, and several types of fruit. They trade for sugar, salt, some processed cocoa and miscellaneous other foods. They drink 40+ oz of hot cacao/cocoa per day, some locally produced and some imported. A little-known secret: the Kuna eat an average of 3 oz of donut a week. They also fish and hunt regularly.

In the first recent study, published in 1997, the Kuna diet is described as 29% lower in fat than the average US diet (56 g/day), 23% lower in protein (12.2 g), 60% higher in cholesterol, and higher in sodium and fiber. The study doesn't specifically mention this, but the reader is left to infer that 65% of their calories come from carbohydrate. This would be from plantains, corn, yucca, sugar and beans. The fat in their diet comes almost exclusively from coconut, cocoa and fish: mostly saturated and omega-3 fats.

In the next study, the picture is beginning to change. Their staple stew, tule masi, is described as being 38% fat by calories (from coconut and fish), exceeding the American average. In the final study in 2006, Hollenberg's group used a more precise method of accounting for diet composition than was used in previous attempts. The paper doesn't report macronutrients as a percentage of calories, and I suspect the reason is that they aren't consistent with the previous papers. They have retreated from their previous position that the Kuna diet is low-fat and describe it instead as "low in animal fat", leaving plenty of room for saturated fats from coconut and cacao.

I was able to find some clues about their diet composition, however. First of all, they report the meat consumption of the Kuna at approximately 60 oz per week, mostly from fish. That's 8.6 oz per day, identical to the American average. They also reported the fat content of the cacao the Kuna produce locally and brew into their favorite 40-oz-a-day drink. It's 44.2% fat by weight. The low-fat cocoa drinks they used to calculate macronutrient totals are made from imported cocoa (cocoa is defatted cacao powder), ignoring the locally produced, full-fat cacao. If we assume half the chocolate they drank was locally produced, that's about 30 additional grams of fat a day, bringing their total fat intake to 8g above the average American. I suspect the authors chose to ignore the locally-produced cacao to lower the apparent fat intake of the Kuna, even though the paper states they drank both regularly.

By putting together the pieces from the later studies, a new picture emerges: a diet high in fish and moderate in protein, high in unprocessed fat (especially saturated and omega-3), and moderate in mostly unprocessed carbohydrate.

Here's my biased interpretation. The Kuna are healthier than their city-dwelling cousins for a number of reasons. They have a very favorable omega3:6 ratio due to seafood, wild game and relatively saturated vegetable fats. Their carbohydrate foods are mostly unprocessed and mostly from non-grain sources. They also live an outdoor life full of sunshine (vitamin D) and exercise. The chocolate may also contribute to their health, but I doubt it's a major effect. They're healthier than industrialized people because they live more naturally.

Another lesson to be learned from the Kuna and other exceptionally healthy indigenous peoples is that the human body can tolerate a fair amount of carbohydrate under the right conditions. Peter discusses another example of this, the Kitavans, on his blog. 50% carbohydrate while sitting in front of a desk all day, eating corn oil and getting no exercise = bad. 45% carbohydrate while hunting, relaxing and preparing whole, natural food in the sun all day = good.