I have long thought that there is more to the obesity epidemic than merely a change in diet, although I do believe that the large increase in the consumption of carbs in general and fructose specifically are exacerbating forces. I’m always on the lookout for something that happened around the late 1970s/early 1980s that might be a major driving force behind the explosion of obesity that we’ve experienced since then.

The epidemiology of the sudden increase in fat deposition in so many people looks like an infectious disease, but I have a problem in buying into that idea whole hog. If it were an infectious disease, I don’t see how the switch to a low-carb diet would make it go away. I suspect that it is probably some sort of environmental contaminant that underlies the situation. The difficulty is in discovering what the factors are and how they work to make us all struggle to keep our weights in check. I doubt that there is one specific catalyst for the entire obesity problem; I would think that a combination of ingredients are probably at fault. But what are they?

I’ve posted on a few previously. In addition to those, a paper recently published online in the journal Environmental Health Perspectives implicates phthalates as another possible agent.

Phthalates are a class of chemicals that are plasticizers. In other words, they turn hard plastics – particularly PVC – into softer, more flexible, ones. Phthalates are also used in cosmetics, shampoos, soaps, lubricants, pesticides, paints, and, strangely enough, rubberized sex toys. (Due to the phthalates in this last, some manufacturers of these objects recommend the use of a condom on the device prior to use.)

Although phthalates are oil soluble like PCBs and dioxins and the other pollutants I’ve posted about before, they are also apparently fairly quickly metabolized and their metabolic by products are excreted in the urine. But while they hang around – and they do hang around because most of us are constantly being exposed – they cause some problems. More than 75 percent of Americans have measurable detectable levels of phthalate metabolites.

One of the actions of phthalates is to act as an anti-testosterone.

Phthalates are known antiandrogens in experimental animal models, with consistent results dating back several decades. Testicular steroid hormone synthesis and reproductive system development in males have been adversely affected by exposure, especially neonatal exposure, to certain phthalates…

And, in males at least, since a lack of testosterone or low testosterone levels have been associated with obesity and insulin resistance, anything that reduces testosterone or negates its effects should cause insulin resistance and/or obesity. The authors of this paper looked for such a correlation.

The researchers used 1999–2002 data from the CDC National Health and Nutrition Examination Survey (NHANES) to look for a correlation between phthalate exposure and obesity and/or insulin resistance in adult men. They compared urine concentrations of six phthalate metabolites to the participants’ waist circumference and measures of insulin resistance while controlling for a variety of potential confounders, including age, ethnicity, fat and calorie consumption, physical activity, and smoking status.

The data show a significant correlation between four of the phthalate metabolites and a larger waist circumference and three metabolites and increased insulin resistance. When subjected to more rigorous statistical analysis taking into consideration liver and kidney function, the researchers found that the associations decreased a little but were still significant for all the metabolites but one.

The paper is available in free full text if you would like to read it in its entirety and look at the graphs showing a dose-response curve effect for these metabolites.

I want to add that this paper in no way ‘proves’ that phthalates cause obesity and/or insulin resistance. What it does show is that there is a correlation between large levels of phthalate metabolites (and presumably phthalites) and an increased waist circumference and insulin resistance. But it is axiomatic that correlation does not imply causation. Actually it does imply causation, but there is really no proof that the one causes the other.

If you look outside and you see a lot of umbrellas you can be pretty sure it’s raining. You look out a little later and see no umbrellas and it’s not raining. After you make these observations a number of times, it would be reasonable to say that umbrellas cause rain because every time you see an umbrella it’s raining. In this case there is a correlation but there is no causation. In fact, there is causation, but it works the other way: the rain causes people to pop out their umbrellas.

The next step to see if there is causation is to give lab animals phthalates to see what happens. In the case of rodents, the effect is smaller than that found in humans. As the authors point out

Associations between certain phthalate metabolites and antiandrogenic effects have also been found in humans at much lower exposure levels than those used in rodent experiments. Suspected metabolites include mono-benzyl phthalate (MBzP), mono-ethyl phthalate (MEP), mono-isononyl phthalate (MiNP), mono-methyl phthalate, and mono-butyl phthalate (MBP). Urinary phthalate metabolites in pregnant women have been found to correlate with subtle genital changes in their infant males, and breast-milk phthalate metabolites have been correlated with shifts in reproductive hormones in infant males.

Although there is no absolute proof that phthalates are a driving force, much less THE driving force, in the development of insulin and obesity, there is enough correlative evidence for me to make me avoid them as much as possible. There are way too many natural products out there that are cosmetics, soaps, shampoos, and even sex toys for all I know to keep me from having to use those products containing phthalates. I would encourage readers of this blog to do the same. Here is a Wikipedia entry on phthalates along with a list of the most common ones so that you can identify them on the labels of products you may be considering. All have phthalate on the end – dimethyl phthalate, for example – so they’re not tough to identify.

Cosmic pizza grease returns! But maybe this time to positive effect. The question is, are you willing to produce a little (maybe a lot) of cosmic pizza grease of your own to rid yourself of polychlorinated biphenyls, dioxins, dichlorodiphenyltrichloroethane and other organochlorine pollutants?

In my daily romp through the medical literature I came upon a paper in the Journal of Nutritional Biochemistry that answered a question I’ve been pondering on for a while? How can we get rid of the almost ungetridable pesticides and industrial pollutants that we all have stored in our tissues?

Organochlorine pesticides (DDT, lindane, etc), organochlorine and organobromine industrial pollutants, solvents, placticizers, and a host of other such substances are in the stored fat of all of us. Their use over the previous decades has so filled our environment with these chemicals that we can’t escape them. The are in the air, they fall in the rain, they are in the groundwater. Consequently, they are in our food. Whenever we eat, we get a load of these persistent organic pollutants (POPs) that make their way into our fat cells and cells in other tissues. And they build up because we can’t get rid of them.

Scientific evidence is mounting that these POPs accumulating in our fat cells might actually make us fat. POPs, especially the organochlorines, have been shown to cause weight gain and difficulty in losing weight in animals. It stands to reason that they should exert similar effects on humans, which could be one of the factors contributing to the worldwide obesity epidemic that has sprung up from nowhere over the last 25 years. No one is certain of the precise mechanism through which these chemicals work to promote weight gain, but more and more researchers are coming to believe that they do.

And no one knows if the levels contained in the average adult cause health problems. It is well known that large doses are extremely toxic, but low doses are a question mark right now. My take on it is that they’re probably not doing us a whole lot of good, and for my money I would just as soon get rid of mine.

Let’s take a look at how these substances accumulate in our fat.

First, the chemical structure of these compounds involves a chlorine-carbon bond that is very stable and lipophilic (fat loving). The stability is what keeps these chemicals around for decades without breaking down, and their lipophilic nature is what drives them into our fat.

When we eat foods that are contaminated with POPs (some foods are contaminated more than others, but virtually all foods contain some quantity of POPs), these foods make their way into our digestive tracts. The gall bladder squirts bile salts, cholesterol and phospholipids into the churned up mass of food as it travels through the first part of the small intestine. The POPs quickly find their way into the fat in this mass, which is then absorbed through the cells called enterocytes that line the small intestine. Once in the enterocytes, the fat – including the POPs – is repackaged and released into the lymph. The lymph containing the POP-laden fat makes its way to the blood, then to the fat cells, which remove most of the POPs and store them away.

Once they reach the fat cells, it becomes difficult to get rid of the POPs for a couple of reasons. First, they like fat, so they want to stay where the fat is. Second, if they do get released from the fat cells during weight loss they get reabsorbed by the enterohepatic circulation.

POPs that leave the fat cells go back into the blood and travel to the liver where they are released into gall bladder as bile. It is thought that these POPs are also released through the enterocytes back into the small intestine. Animal studies have shown both mechanisms to be at work. When the POPs reach the small intestine either through the bile or through the enterocytes, the process described a couple of paragraphs above repeats. The POPs mix with the fat and are absorbed and start their journey back to the fat cells once again. The process of releasing a substance (in this case POPs) by the liver into the intestine and having it picked back up again and recycled is called enterohepatic circulation.

If you are reducing food intake to lose weight these POPs traveling back into the blood make their way once again to the fat cells, but are released quickly as the fat cells give up their fat to provide the energy deficit created by the decreased food intake. What ends up happening is this flux of POPs from the intestine to the fat cells and back leads to increased POP levels in the blood and the uptake of POPs by other tissues such as the brain. I don’t know about you, but I would much prefer my POPs stay in my fat and away from my brain, kidneys, pancreas, etc. But what if I want to lose weight, what then? And is there a way to reduce the body’s load of POPs permanently?

We’ve got a situation that’s really a one way street. POPs can get in, but they can’t get out. All they can do is recirculate. And since they’re always coming in, we’re always going to have more and more of them accumulate. Which I have always found troubling because it seems that at some point they will begin to cause serious problems.

Hence my excitement when I came across and article titled “Enterohepatic circulation of organochlorine compounds: a site for nutritional intervention” in the above-mentioned journal.

The authors start off with some pretty frightening statements:

There is ample evidence that OCs [organochlorine compounds] are present in humans. Studies of breast milk composition have revealed the international presence of OCs. A memorable demonstration of the ubiquitous distribution of OCs in humans resulted from a meeting of 13 European Health ministers in June 2004. All of the ministers volunteered to have OCs measured in their blood, and most of the assayed OCs were found in all of the ministers.

There are also reports that the level of OCs in blood increases with age. This longitudinal increase results only if the rate of intake is greater than the rate of excretion. [My italics]

Since the presence of OCs in the human food chain will continue for decades, it is unlikely that cessation of production of OCs will contribute significantly to health in the foreseeable future. We therefore need to consider alternative approaches to potential health problems resulting from OCs. One approach is that of reducing the human body burden of OCs by nutritional means. We present here data that suggest that it is possible to reduce the rate of intake of dietary OCs and to increase the rate of excretion of OCs.

So we only accumulate if our intake is more than our excretion. But how do we excrete POPs? We excrete them in our stools. But unfortunately, only in minuscule amounts. These compounds are trapped in fat, and we absorb almost all the fat that gets into our GI tract. There is a tiny amount of fat that makes its way out in the stool, maybe 5 -7 grams per day, which is negligible in terms of shedding and meaningful amounts of POPs.

So, if we could figure out a way to reduce the absorption of fat back into the body, then more POP-laden fat would come out in our stools and be gone forever. And if we could figure out a way to lose weight, which increases the dumping of POPs into the small intestine AND decrease the reabsorption of it all, we could really make a substantial dent in our total body POP load.

Well, the good news is that we can! The bad news is that it comes at a price. The price? We have to become producers of cosmic pizza grease.

I posted a few weeks ago on the fact that orlistat, a drug that blocks fat absorption in the small intestine, had been approved for over the counter use. Orlistat can help you increase the fat in your stool and reduce your body load of POPs.

The authors of the study gave orlistat to rats that they had loaded up with human-sized amounts of POPs (rats don’t live as long, so don’t have the same tissue quantities of POPs as we and other longer-lived species do) and demonstrated that giving the rats orlistat markedly increased their fecal discharge of the chemicals. The researchers also put the rats on a diet and found that blood levels of POPs skyrocketed. When they gave the dieting rats orlistat they found that the drug caused a much greater excretion of POPs than when administered during the non-dieting state.

I trolled around and found another paper in the American Journal of Physiology (AJP) from a couple of years ago (click here to download a full text version) showing the same phenomenon when animals were fed olestra.

Olestra is a fat substitute made by Proctor & Gamble (P & G) that is not absorbed in the small intestine and makes its way on through. P & G thought they had a gold mine when they came up with olestra because it tastes like fat, cooks like fat, but doesn’t absorb. People could have chips and snacks and all kids of formerly high-fat foods, yet have no fat because olestra doesn’t absorb. The folks at P & G could hear the cash registers ching ching chinging–they were going to be rich, RICH, RICH.

But their plans were dashed because olestra, when consumed in large amounts, causes the same problems that orlistat does: cosmic pizza grease. So, people could only eat small amounts of the olestra-prepared chips and snacks, and who wants to eat only small amounts of these chips and snacks? I guess some people did, but only once.

The AJP article shows that the combination of caloric restriction and olestra brought about a 30-fold increase in excretion of POPs relative to an ad libitum diet, and that the uptake of POPs by the brain during the calorically-restricted diet was reduced by 50 percent.

Does it work the same in people? Probably. There are a couple of studies out there where victims of huge doses of POPs were treated by substances that bind fat in the small intestine, allowing it to continue on its course with its load of POPs.

If you want to reduce your load of POPs, here’s the program I would follow. In fact, I probably will do it at some point, I just haven’t decided when yet.

First, switch to organic foods as much as possible. Organic foods still have some contamination since it comes from the air, rain, and groundwater, but won’t have as much as conventionally grown produce.

Buy local as much as possible because the transport process can add POPs to the food.

Always, always, always wash produce before you eat it, preferably with a little soap, which will attract the POPs.

By following the above instructions, you can reduce as much as possible the POPs coming in.

To increase the amount going out, you’ve got to increase the fat content of your stool. You can do that a couple of ways. You can get orlistat when it is available. It will come in 60 mg capsules, which are half the dose of the prescription version. The standard prescription of the full bore stuff is 120 mg three times per day before meals. Based upon the chart below, you get the most bang for your orlistat buck at about 200 mg per day.

You could take four of the OTC capsules daily and pretty much get most of the benefit you’re going to get. I would take one before each meal and two before the meal containing the most fat.

The second thing you could do if you don’t like the orlistat option is to go to the grocery store and get some Lay’s Light potato chips or some other snack made with olestra (trade name: Olean), figure out how much you would have to eat to get about 15-20 grams of the stuff and have at it.

Both of these methods should reward you with the production of plenty of cosmic pizza grease, but, unfortunately, maybe not at the specific times you might want to welcome it. So, this detox regimen would be best carried out over a weekend when you can stay around the house and close to the john.

To really make the program work better, you should go on a low-cal diet starting a day or so before you start either the orlistat or the olestra to mobilize the POPs for better elimination. During your detox, you should keep the calories down but eat some fat at each meal so that the gall bladder contracts and squirts out the POP-laden bile so that the chemicals can be removed and carried away in the fat or in the faux fat (olestra).

I haven’t found any studies on humans checking for the amounts of POPs removed using this method, but I would figure it would be a fair amount. If you keep large quantities from going in and periodically sacrificing a weekend to hugely increase the quantities going out, you should get rid of most of your accumulation of PCPs over time. Will you feel better? Will you lose more weight? Will you live longer? I haven’t a clue, but I can’t imagine that you would be worse for it. I would think that the less POPs you have on board the better.

The orlistat/olestra detox maneuver is certain to remove POPs. But are there other ways that are less cosmic?

Serendipitously, in the same issue of the Journal of Nutrirional Biochemistry containing the orlistat detox article there is another about the use of green tea and its catechins to prevent the absorption of fat in the intestine.

Based on the information available thus far, it is evident that green tea and its catechins effectively lower the intestinal absorption of lipids. Among the green tea catechins, EGCG is the most potent inhibitor of lipid absorption. The potent inhibitory effect of EGCG appears to be associated with its ability to form complexes with lipids and lipolytic enzymes, thereby interfering with the luminal processes of emulsification, hydrolysis, micellar solubilization, and subsequent uptake of lipids. EGCG appears to be more effective in lowering the absorption of lipids of extreme hydrophobicity, such as cholesterol and α-tocopherol, with little or a moderate effect on less hydrophobic lipids such as retinol and fatty acid. It is probable that green tea or it constituents lower the absorption of other lipophilic compounds such as POPs. Further studies are warranted to define the mechanisms underlying the inhibition of lipid absorption by green tea and its catechins.

A search on PubMed indicates that calcium is also pretty good at binding intestinal fat and preventing its uptake. There is some controversy over whether calcium supplements will prevent the absorption or if it is only calcium as a component of dairy products that works. See if you can guess which side the dairy industry came down on.

You can probably do a mini-detox with the green tea (or green tea extracts containing the catechins) and calcium without the appearance of cosmic pizza grease, but I don’t know how effective the mini-detox would be as compared to the full thing. If you do try a mini detox, I would make sure to take some magnesium along with the calcium.

Once again, let me hasten to repeat, I have never tried this method of detox myself and have never used it on patients. The science underlying it appears sound, and I don’t think it should cause problems if pursued over a couple of days now and again, but I’m not recommending or advocating it. I’m merely putting it up because I think it will be of as much interest to the people reading this blog as it is to me.

If and when I do try it myself (or more likely, try to talk MD into doing it), I will blog on my (her) experiences post haste.