Yet, this week another study was published which strongly suggests that our weight is not, by any means, soley governed by what we eat. Rather, it is mediated by factors out of our control, one of them being the balance of chemicals in our bodies.

In a recent paper, published in the Annals of the New York Academy of Sciences, researchers at the Institute of Molecular and Cellular Biosciences Institute at the University of Tokyo in Japan explain two molecular pathways that directly affect the formation of adipocytes, another name for fat cells. At the center of both pathways is the nuclear receptor PPAR-gamma, a receptor that is also at the heart of the immune response.

It turns out that PPAR-gamma plays a fundamental role in determining the fate of undifferentiated bone marrow cells. According to the researchers, bone marrow cells start out as mesenchymal cells – basic cells that under the influence of different chemical signals, can be converted into several different types of cells. If they receive a certain signal, the cells turn into bone cells called osteoblasts. If they receive other signals, they turn into adipocytes, adding to a person’s body weight.

When PPAR-gamma is active, it regulates a set of signals that enhance the formation of adipocytes rather than osteoblasts. This reality has been confirmed by other studies, including some which have shown that diabetes patients given a drug that enhances the activity of PPAR-gamma show a greater rate of adipocyte formation.

What follows is that if the activity of PPAR-gamma is slowed or blocked, mesenchymal cells should follow the opposite course. Rather than turn into adipocytes, more of the cells should remain as osteoblasts, causing a person to loose, rather than gain weight.

The University of Tokyo team was able to elucidate two pathways whose end components block the activity of PPAR-gamma. Interestingly, one of these pathways is mediated by the inflammatory molecules TNF-alpha, IL-1 and Nuclear Factor Kappa B – inflammatory markers that are released by the immune system in response to the Th1 pathogens. In a series of experiments that tested the effects of increased cytokine production on mouse bone marrow stromal cells, the team discovered that a chemical cascade activated by TNF-alpha, IL-1 and Nuclear Kappa Factor B blocks the ability of DNA to bind to PPAR-gamma, thus slowing the activity of the receptor. The result: a decrease in the number of mesenchymal cells converted into adipocytes.

At this point you may be thinking – but a decrease in the number of adipocytes would lead to weight loss. That’s correct. It’s important to keep in mind that many people who develop Th1 disease actually lose weight. This was certainly true in my case. As I started to fall ill with CFS, I lost so much weight, while continuing to eat around the same amount of food, that I was accused of being anorexic or bulemic. Nobody believed me when I tried to communicate that my weight loss seemed to be out of my control.

So, if the above pathway is accurate, then why do many people with Th1 disease gain weight? The reality is the above pathways is probably just one of many yet to be discovered that affects weight regulation. Also, based on gut bacteria studies that I discuss elsewhere on this site, it’s becoming abundantly clear that obesity is, like any other Th1 disease, a bacterial illness. So perhaps those individuals who accumulate enough obesity causing bacteria find that the presence of these pathogens allows for weight gain that offsets any weight loss that might result from the deactivation of PPAR-gamma described above. Other variables that must be factored into the picture, such as the carbohydrate craving frequently experienced by people with Th1 disease that can lead to weight gain. Just like other factors that govern the progression of chronic inflammatory disease, it appears that weight regulation is incredibly complex. As biomedical researcher Trevor Marshall has commented, “at this point the complexity of the body is so imponderable that we must deal with a certain level of uncertainty.” Still, studies like that conducted by the Tokyo researchers have great potential to lead us in the right direction.

The bottom line is that a person’s ability to gain or lose weight, particularly if they have a Th1 disease, is largely out of their control. The above study makes it clear that fat cell production is largely regulated by a complicated chemical pathway, rather than the consumption of a Big Mac. As research in this area continues, the idea that becoming fat or thin is only related to lifestyle choice should become somewhat obsolete. This doesn’t mean that people who ingest huge amounts of food won’t gain weight, or that people who go on strict diets won’t lose weight (at least temporarily), only these factors will become one many other variables to affect body mass.

The Univeristy of Tokyo study is also of interest when one considers that the statins and the sartans (two classes of drugs) bind PPAR-gamma. Olmesartan, also called Benicar, is the sartan taken several times a day by patients on the Marshall Protocol. Olmesartan has a high affinity for PPAR-gamma, and very likely acts as an antagonist of the receptor (slows it’s activity). Thus, Olmesartan should technically make it a little easier for a person to maintain a healthy weight since by blocking PPAR-gamma, it should slow the formation of adipocytes. Indeed, some patients on the Marshall Protocol find that Benicar helps their weight to stabilize.

Other sartans such as Telmisartan and Ibersartan also bind PPAR-gamma with a high affinity (and are also likely antagonists). Among the statins, Simvastatin, Lovastatin, and Atorvastatin have similar properties. The fact that these drugs may affect fat cell formation is certainly also food for thought.

Among Gordon’s findings was the fact that his obese and lean volunteers had substantially different compositions of bacteria in their guts. Obese volunteers had 20 percent more of a bacterial species called firmicutes in their gut, but harbored almost 90 percent less of another bacterial species called bacteroidetes than lean volunteers.

Interestingly, when obese subjects were put on a low-carb, low-fat diet, the composition of the bacteria in their guts started to adjust to more closely resemble the ratios of bacteria seen in their lean counterparts.

Similarly, the team found that mice injected with gut bacteria from other obese mice gained about twice as much weight as mice injected with bacteria taken from the stomachs of lean mice, strongly suggesting a direct relationship between the relative abundance of certain bacteria in the gut and the tendency of an individual to gain weight.

This week, a new study revealed similar findings, demonstrating that the mix of bacteria in a baby’s gut may predict whether the infant will become overweight or obese later in life.

In a study published in the March issue of The American Journal of Clinical Nutrition, researchers at the University of Turku in Finloand reported that babies with high numbers of the bacterial species Bifidobacteria and low numbers of the bacterial species Staphylococcus aureus may be protected from excess weight gain.

The Finnish team selected 49 children from a larger long-term study aimed at evaluating the effect of probiotics on allergic disease. The babies had been evaluated at birth, five more times before age 2, and then again at ages 4 and 7. The researchers in the original study had also tested for intestinal microbes in fecal samples collected at 6 months and 12 months.

Of the 49 subjects selected from the larger study, 25 were overweight or obese at age 7, while 24 subjects of the same age were of normal weight.

When the Finnish team examined the fecal samples taken from the children earlier in life, the average bacterial counts of Bifidobacteria taken at 6 months and 12 months were twice as high in those children who were at a healthy weight as in those who had become obese.

Those who stayed at a healthy weight also had lower fecal S. aureus levels at 6 months and 12 months than did those who got heavy.

The researchers speculated that S. aureus may trigger low-grade inflammation that also contributes to developing obesity, a statement which supports biomedical researcher Trevor Marshall’s view that obesity is not a cause for other diseases such as heart disease and stroke, but is an inflammatory disease in its own right. As with other chronic diseases, it is directly related to a patient’s bacterial load.

Since Bifidobacteria are prevalent in the guts of breast-fed babies, the Finnish team also suggested that their findings may help explain why breastfed babies have been found to be at lower risk for later obesity. Other studies have repeatedly found that breastfed babies have a 13 to 22 percent reduced risk of excess weight or obesity in childhood.

“The finding that the lean children harbored higher levels of Bifidobacteria at younger ages is very intriguing,” commented Ruth Ley, a research assistant professor at Washington University School of Medicine in St. Louis. According to Ley, the Finnish study is unique, because it collected information over several years, making it possible to look for differences in gut microflora.

Someday, the Finnish researchers speculated, tinkering with gut flora may help prevent or treat obesity. Little do they know (at least we presume so) that patients on the Marshall Protocol are already doing much more then simply tinkering with the pathogens in their guts. By using a combination of low-dose antibiotics and Benicar they are able to gradually wear away at pathogenic species in the gut, allowing their GI tracts to re-establish an optimal composition of gut flora after several years of therapy.

Obese individuals have different populations of microbes

Gordon’s two recent studies, which were published in a 2006 issue of Nature, describe a direct relationship between the relative abundance of certain bacteria in the gut and the tendency of an individual to gain weight.

All humans have trillions of bacteria living in the gut. Their role is to combat pathogens and break down food. In 2004, Gordon proposed that these microbes might play a role in controlling body weight.

Gordon theorized that certain bacteria have the ability to harvest energy more effectively than others. Bacteria in the gut are able to extract many of the nutrients from the foods with which they come in contact. If some species of bacteria are better at harvesting these nutrients than others, then people with more energy efficient bacteria might absorb more calories and gain weight more easily.

Gordon tested his hypothesis on twelve obese volunteers and five lean volunteers. He used genetic sequencing to identify the different species of bacteria in the subjects’ guts.

The majority of the bacteria he identified fell into two groups – the firmicutes and the bacteroidetes. However, the sequencing showed that the obese volunteers had 20 percent more firmicutes and almost 90 percent less bacteroidetes than the lean volunteers.

There are 274 genera of firmicutes. Although most firmicutes have cell wall structures, some of the species lack cell walls altogether, just like the CWD bacteria that Marshall implicates in chronic disease. Both forms of bacteria cannot be detected by conventional laboratory tests.

After the gut bacteria of the obese and lean subjects had been screened, the obese volunteers spent one year on a low-fat, low-carbohydrate diet and lost 25 pounds. When Gordon screened their bacteria again, he found that, as the volunteers lost weight, the composition of the bacteria in their guts started to adjust to more closely resemble the ratios of bacteria seen in their lean counterparts. The percent of firmicutes dropped and the percent of bacteroidetes rose.

Creating obese mice

Gordon’s team performed a follow-up study on mice. The researchers sucked the gut microbes out of both lean or obese mice and injected them into the small intestines of a different group of mice that had been specially bred with bacteria removed from their intestines.

After two weeks, the mice that had been injected with gut bacteria from the obese mice gained about twice as much weight as the mice injected with bacteria from the lean group.

The researchers also screened the gut bacteria of another group of mice that had been genetically engineered to be obese. They found that, just like the human subjects previously tested, the obese mice also had a higher percentage of firmicutes in the gut. Interestingly, they also found that the gut bacteria of obese mice had more genes that allow them to break down otherwise indigestible fibrous parts of food.

Indeed, when Gordon’s team charted the amount of food the mice consumed and the resulting calorie content in the animal’s feces, they confirmed that it was easier for the obese mice to assimilate nutrients.

The relevance of the vitamin D receptor (VDR) to obesity

Marshall’s research supports the idea that firmicutes may play a role in obesity, along with the other cell wall deficient (CWD) and biofilm bacteria he implicates in chronic disease. There are over 50 species of bacteria able to transform into the cell wall deficient form. Marshall believes that the ability of CWD bacteria and firmicutes to proliferate is directly related to suppression of the vitamin D receptor (VDR).

Critically important to the body, the VDR controls the innate immune system, the body’s first line of defense against infection. It’s also responsible for turning on and off a wide array of genes and chemical pathways.

One of the VDR’s myriad functions is that it directly controls the expression of the antimicrobial peptides (AMPs). The AMPs are proteins that kill bacteria by fragmenting DNA.

Although casually referred to as a vitamin by some members of the medical community, molecular biologists have long realized that the precursor form of vitamin D (25-D) is a steroid. In a presentation at the 2006 American Association of Environmental Medicine Conference, Marshall used molecular modeling to show that 25-D binds and inactivates the VDR, which subsequently slows the immune response.

More recently, Marshall used molecular modeling to show that a protein called capnine, which is produced by certain species of biofilm bacteria, can also bind and inactivate the VDR is a manner similar to 25-D. He believes that other types of pathogens including viruses, mycoplasma and possibly even fermicutes may also produce proteins that act in a manner similar to capnine.

Since the VDR must be activated in order to express the AMPs, individuals who are infected with CWD and biofilm bacteria, and consuming high levels of 25-D are no longer able to produce the AMPs.

The AMPs play a critical role in keeping the bacteria in the small intestine in check. Healthy individuals appear to have some firmicutes in the gut. However, in individuals who no longer produce enough AMPs, fimicutes may find it much easier to proliferate.

Connection between obesity and chronic disease

Based on these observations, it would seem that the current epidemics of obesity and chronic disease go hand in hand. Many patients with chronic disease certainly find it increasingly difficult to maintain a healthy weight as their illness progresses.

At the moment, most doctors tell their overweight and obese patients that extra body fat is CAUSING them to develop diseases such as athroclerosis and diabetes. But it is now becoming increasingly clear that obesity is not a cause for disease but is a disease itself. As with other chronic diseases, it appears to be directly related to a patient’s bacterial load. This means that the reason that patients with heart disease and diabetes tend to be obese may simply due to the fact that these individuals have accumulated high amounts of L-form/biofilm bacteria that have shut down the Vitamin D Receptor, making it easier for them to accumulate the pathogens that cause weight gain.

In a 2004 presentation to the FDA, Marshall used molecular modeling to show that the medication Benicar is able to bind and activate the VDR. The Marshall Protocol, Marshall’s treatment for chronic disease, uses Benicar to restore functionality to the VDR, renewing the body’s ability to turn on the innate immune system and produce the AMPs.

This means the immune system is once again able manage other pathogens, including some of the pathogenic forms of firmicutes. At the same time, patients take carefully selected antibiotics over a period of several years to eliminate disease-causing bacteria. With these measures in place it seems likely that individuals will have more optimal gut bacteria that do not promote obesity.

Although more research must be done in order to determine the direct impact of the MP on gut bacteria, several previously overweight patients who have returned to normal health through MP therapy report that significant weight loss accompanied their recovery.

Just like rheumatoid arthritis, sarcoidosis, CFS and other chronic diseases, obesity runs in families, suggesting that firmicutes and other bacteria that may influence weight might be passed from generation to generation by incorporating their genetic material into host DNA.

Several months ago, doctor-researchers at Harvard Medical School and the University of California published a study about obesity in the New England Journal of Medicine. The scientists analyzed 32 years of obesity data on more than 12,000 people who had participated in a study for heart disease. They used a database of contact information to map each participant’s social network — the array of the friends and family they named over the years and then traced obesity trends through the network.

The team found that people’s odds of becoming obese increase by 57% if they have a friend who becomes obese, 40% if they have a sibling who becomes obese, and 37% if a spouse becomes obese. They concluded that obesity is “socially contagious,” claiming that people copy the eating habits of the those around them and tend to follow suit when their friends and family become obese or lose weight. More likely, obesity is contagious and pathogens such as firmicutes are passed among people in close contact.

In 1999, the NIH funded a $200,000 study that tested an intervention program on two groups of Navajo school children. The intervention, which was only performed on one of the groups of children, involved a substantial increase in physical education programs, classes about nutrition, significant reduction in fat and calorie content of all school meals, and several other health related measures.

The primary goal of the study was to reduce the rate of body fat in the intervention group, but after the three-year intervention the percent of body fat in both groups was essentially identical. The researchers were unable to explain the failure of the intervention.

Similarly, a recent study published in the British Medical Journal found that the percentage of body fat in preschool children in six nursery schools in Glasgow, Scotland was not affected by a similar diet and exercise intervention program.

The preschoolers were divided into two groups. One group participated in the intervention program, which consisted of increasing the children’s level of physical activity (they performed three 30 minute exercise sessions a week over 24 weeks) plus home based health education aimed at increasing physical activity through play and reducing sedentary behaviour. The team found that the children in the intervention group developed better motor skills than those in the control group, but the intervention program had no effect on their body mass index.

In fact, there are only spurious connections between low-fat diets and heart disease. In his book “Good calories, Bad calories”, Gary Taubes explains that Nineteenth-century Americans consumed huge amounts of meat: the percentage of fat in the diet of ancient hunter-gatherers, according to the best estimate today, was as high or higher than the ratio in the modern Western diet. Furthermore, when the theory that low-fat diets afford protection against coronary heart disease has been tested in clinical trials, the evidence keeps turning up negative. As Taubes notes, the most rigorous meta-analysis of the clinical trials of low-fat diets, published in 2001 by the Cochrane Collaboration, concluded that they had no significant effect on mortality.

Clearly the vast majority of doctors and researchers studying obesity are missing a major part of the picture. It is impossible for seriously overweight people who have accumulated high bacterial loads to starve themselves in order to resolve their weight issues. How many of us have a friend or family member who cannot lose weight despite their continuous attempts to eat healthy food and exercise? It is time that these people stop being blamed for their inability to shed pounds and instead become informed of the treatment that will allow them to target the bacteria causing their disease. If no measures are taken to control the bacteria that contribute to obesity, the results of the above studies suggest that diet and exercise have little effect.

It’s not surprising then, that obesity and chronic disease are still alarmingly on the rise.

A team of researchers at John Hopkins University released a statement saying that if people keep gaining weight at the current rate, 75 percent of U.S. adults and 24 percent of U.S. children will be overweight or obese by 2015. Similarly, according to the CDC, seven of every 10 Americans who die each year, or more than 1.7 million people, die of a chronic disease.

March 2008 update:

This week, a new study revealed similar findings, demonstrating that the mix of bacteria in a baby’s gut may predict whether the infant will become overweight or obese later in life.

In a study published in the March issue of The American Journal of Clinical Nutrition, researchers at the University of Turku in Finloand reported that babies with high numbers of the bacterial species Bifidobacteria and low numbers of the bacterial species Staphylococcus aureus may be protected from excess weight gain.

The Finnish team selected 49 children from a larger long-term study aimed at evaluating the effect of probiotics on allergic disease. The babies had been evaluated at birth, five more times before age 2, and then again at ages 4 and 7. The researchers in the original study had also tested for intestinal microbes in fecal samples collected at 6 months and 12 months.

Of the 49 subjects selected from the larger study, 25 were overweight or obese at age 7, while 24 subjects of the same age were of normal weight.

When the Finnish team examined the fecal samples taken from the children earlier in life, the average bacterial counts of Bifidobacteria taken at 6 months and 12 months were twice as high in those children who were at a healthy weight as in those who had become obese.

Those who stayed at a healthy weight also had lower fecal S. aureus levels at 6 months and 12 months than did those who got heavy.

The researchers speculated that S. aureus may trigger low-grade inflammation that also contributes to developing obesity, a statement which supports biomedical researcher Trevor Marshall’s view that obesity is not a cause for other diseases such as heart disease and stroke, but is an inflammatory disease in its own right. As with other chronic diseases, it is directly related to a patient’s bacterial load.

Since Bifidobacteria are prevalent in the guts of breast-fed babies, the Finnish team also suggested that their findings may help explain why breastfed babies have been found to be at lower risk for later obesity. Other studies have repeatedly found that breastfed babies have a 13 to 22 percent reduced risk of excess weight or obesity in childhood.

“The finding that the lean children harbored higher levels of Bifidobacteria at younger ages is very intriguing,” commented Ruth Ley, a research assistant professor at Washington University School of Medicine in St. Louis. According to Ley, the Finnish study is unique, because it collected information over several years, making it possible to look for differences in gut microflora.

SOURCES

Caballero, B., Clay, T., Davis, S. M., Ethelbah, B., Rock, B. H., Lohman, T., et al. (2003). Pathways: a school-based, randomized controlled trial for the prevention of obesity in American Indian schoolchildren. The American journal of clinical nutrition, 78(5), 1030-8.

Christakis, N. A., & Fowler, J. H. (2007). The Spread of Obesity in a Large Social Network over 32 Years. N Engl J Med, 357(4), 370-379.

Marshall, T. (2007). Bacterial Capnine Blocks Transcription of Human Antimicrobial Peptides. Nature Precedings.

Marshall, T. G., & Marshall, F. E. (2004). Sarcoidosis succumbs to antibiotics–implications for autoimmune disease. Autoimmunity reviews, 3(4), 295-300.

Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., Gordon, J. I., et al. (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122), 1027-131.

Wang, Y., & Beydoun, M. A. (2007). The obesity epidemic in the United States–gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis. Epidemiologic reviews, 29, 6-28.