Truths and Mistruths of Science of Weight Gain and Obesity

Majid Ali, M.D

 Misinformation about the science of health, eating depleted and denatured foods, and chemicalization of our cells  — put them together and you have a very effective prescription for causing  a massive epidemic of obesity. All those factors eventually lead to oxygen dysfunction (dysoxygenosis) in fat cells (adipocyte) and muscle cells (myocytes). That, simply stated, is the tragedy of epidemics of obesity and diabetes that we witness today. If we wish to understand the links between obesity and many other disorders, again we need to consider the basic scientific aspects of oxygen homeostasis, cellular energetics and energy homeostasis in the body.


 In 2004, in an article entitled “Hypothesis: Obesity Is Adipomyocytic Dysoxygenosis,” I introduced the concept that excess body weight that cannot be lost by ordinary efforts of reduced caloric intake and increased physical activity is a cellular oxygen deficiency state caused by impaired mitochondrial function (the dys-ox state) in adipocytes and myocytes.1 In that “adipomyocytic dysoxygenosis (AD) model,” the fundamental electron transport enzymatic pathways that initiate metabolic events and sustain a robust metabolism  — and an optimal weight — are injured by toxic foods, toxic environment, toxic emotions, and toxic thinking. In persistent obesity, adipocytes are increased in number and distended with fat. More importantly, the mitochondria are dysfunctional and the cells have impaired oxygen utilization. That, simply stated, is the root cause of the spreading epidemic of obesity in the United States and elsewhere in the world. For the general readership, I also published a second article entitled “Oxygen Is Cellular Oxygen Deficiency State,” to provide a rational and scientifically sound approach to achieving and maintaining an individual’s optimal weight.2


Three Furies of Obesity

Excess fat in the adipocyte is oxidizing. Excess oxidation in the adipocyte impairs cellular oxygen utilization. Adipocyte dysoxygenosis so produced evokes”molecular inflammation” in the cell. Molecular inflammation in adipose tissue activates macrophages and vascular endothelial cells, and so sets the stage for cellular inflammation. Adipose inflammation so produced further stokes the oxidative fires in adipocytes. More fat, more oxidation, more oxygen dysfunction, more inflammation — the cycle perpetuates itself,  increasing the degrees of oxidosis, acidosis, and dysoxygenosis (the three furies of obesity). That, simply stated, is the inflammatory theory of obesity.

The adipomyocytic dysoxygenosis model of obesity is distinct from the views of obesity held by purists in the fields of clinical bariatrics, energy homeostasis, and genomics  on the one side and the authors of weight control books, who with uncommon exceptions are mere ghost writers for the enormously rich weight control industry. The adipomyocytic dysoxygenosis model of obesity  —  in my view  — is superior to other prevailing notions for the following six principal reasons:

  1.  It holds the cellular energetics and energy homeostasis in the muscle and fat cells as its two centerpieces, which simply cannot be optimally maintained without daily physical exercise.
  2.  It focuses on the issue of altered cellular metabolism as the primary phenomenon in the causation of obesity, rather than on gene mutations currently in fashion among academics.4-8.
  3.  It makes a sharp distinction between foods and ecologic factors  that preserve cellular oxygen homeostasis and those elements that put it in jeopardy, rather than engage in meaningless low-carb/low-fat debates.9-17
  4.  It addresses the critically important factors of food allergy and related adverse food effects, as well as large variations among individuals in their requirements for nutrients. Those factors are taken into account neither by promoters of various weight loss diets nor by the academics.18-22
  5. It has a strong explanatory power for molecular pathways that link obesity to coronary heart disease, cancer, and other disorders discussed in a later section. 
  6. It provides sound scientific basis of integrative plans to effectively address the problem of obesity, rather than the use of drugs like leptin,  dexfenfluramine (taken off the market) and sibutramine (modulators of serotonin), and others, none of which have proven safe and effective in the long run.23-27



As for the academicians preoccupied with genomics of obesity, I do not foresee they are going to be very helpful to two thirds of Americans who are overweight. Those academicians seem not to have learned yet that food fuels the furnace of human metabolism and exercise stokes it fires. Lest some reader think I am overly dramatizing my case, consider the following quote from The New England Journal of Medicine: 
 The January 7, 1865, issue of Harper’s Weekly published instructions on weight loss that are not so different from the advice offered by sensible physicians today. Advances in the treatment of obesity have been made since then, but we must acknowledge that they are not sufficient. In contrast to these pallid therapeutic advances, our understanding of the mechanisms of obesity has improved substantially in the past 20 years. In the early-to-mid-1980s, revolutionaries such as Stunkard published convincing data that human obesity had an inherited component and sparked an explosion of research on the genetic and biologic underpinnings of obesity.28

Advances in the treatment of obesity have been made since then! That is a misstatement if there ever was one on the subject. What the Journal considers advances in the treatment of obesity have utterly failed in the United States, where three out of every five persons now are overweight or obese. Not only has the mainstream medicine — essentially a medicine of pharmacologic blockade — not brought forth any benefits, in my view it has significantly contributed to the problem by ignoring the real issues and injudiciously prescribing drugs that slow down the metabolism.

Now consider the following quote in a recent review of obesity in Nature:

The global epidemic of obesity results from a combination of genetic susceptibility, increased availability of high-energy foods and decreased requirement of physical activity in modern society.29

Amazingly, Nature, one of the most, if not the most, prestigious science journals in the world completely fails to address the elements that threaten redox equilibrium and oxygen homeostasis — related to highly processed foods, environmental pollutants, and emotional stresses — that impair or block enzymes of Krebs and other catabolic pathways. The case of peddlers of ‘obesity drugs’ is the same. Consider the following quotes from Nature:   
 Whatever happened to leptin? Just five years ago, it seemed that a single protein might reverse the rising tide of obesity. What worked for mice has not yet translated to people…. By any reckoning, US$20 million is a lot to spend on a protein. But in May 1995, Amgen of Thousand Oaks, California, paid just that for the commercial rights to leptin, a hormone that made fat mice slim. Identified only six months earlier, leptin could be injected into grotesquely obese, leptin-deficient mice where it curbed their voracious appetites and boosted their metabolic rates. Within a month, and with no apparent side-effects, these mice lost almost half of their excess weight.30

Leptin, of course, was touted as the wonder drug fully capable of killing the dragon of obesity.31,32 Now, nearly ten years later, it is clear that script was written to divest gullible investors of their hard-earned retirements. Clinical trials so far have failed to show any merits of the hormone.

As for links between obesity and chronic diseases—the cardiovascular diseases, diabetes, cancer, and others —consider the following quote from Nature Insight-Obesity:

For reasons that are not fully known, obesity is associated with an increased risk of hypertension, heart disease, diabetes, and cancer.33

It seems safe to predict that preoccupation with obesity genes will not reveal the fundamental links between obesity and any of the diseases mentioned in the above quote. Nor will that be achieved by loud quarreling among  enthusiasts of low-carb and low-fat diets. Obesity, at its core, is a problem of molecular energetics. And molecular energetics, at its core, is a matter of redox equilibrium and oxygen homeostasis. I return to this crucial issue in a later section.


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