By Joel Brind
For many of us, the downside of the holidays is the dread of adding a few pounds of abdominal fat that will take more than a New Year’s resolution to work off. Even worse, we all also know that it’s the extra abdominal fat that causes insulin resistance and eventually—or maybe already—type 2 diabetes.
But more recent research tells a more precise—and cheerful—story about what is really going on. It’s not the actual fat (adipose) tissue that causes the problem after all: It’s the immune cells—the macrophages, to be specific—that are embedded in the adipose tissue, that stir up the trouble.
So why do the macrophages get stirred up, and what do they do that’s so damaging as to ultimately cause diabetes and all the morbidity and mortality that follows? The last two decades of research has demonstrated that excess abdominal fat—because of the associated macrophages—causes a condition of “metabolic inflammation” in the whole body. This systemic inflammation is characterized by elevated inflammatory markers in the blood, most notably a hormone called Tumor Necrosis Factor-alpha (TNF-α). We now know that TNF-α does a double whammy by directly causing insulin resistance in skeletal muscle AND the inhibition and ultimate destruction of the beta cells of the pancreas (the cells that make insulin).
A little more background is in order here: Insulin is the hormone secreted by the beta cells of the pancreas in response to and/or the anticipation of the rise in blood glucose (blood sugar) that happens after a carb-rich meal. What insulin actually does is command mainly three types of tissue: liver, adipose (fat) and skeletal (voluntary) muscle to get that glucose out of the circulation as quickly as possible, by burning it or storing it. These tissues can store glucose as glycogen (aka “animal starch”) or fat. What insulin does is to turn on the enzymatic machinery to store (or burn, in the case of muscle), as well as to open up specialized channels (called “GLUTs”; short for “glucose transporters”—pun intended by the creative researchers that came up with the term) in the cell membranes of adipose and muscle cells, so that glucose can be taken up rapidly by these tissues.
Trouble is, TNF-α, secreted by the activated macrophages embedded in the adipose tissue, directly interferes with the muscles’ deployment of GLUTs in their cell membranes, so they cannot take up glucose readily. This is manifest as the pre-diabetic condition known as “insulin resistance”. As a result, the pancreatic beta cells respond by cranking out more and more insulin. But at the same time, TNF-α also directly interferes with the ability of the beta cells to make insulin, and ultimately induces their self-destruction, causing actual type-2 diabetes. The reason this takes some years to occur is the existence of other chemical control mechanisms—hormones and other factors secreted by muscle cells and other types of pancreatic islet cells that help to protect the existence and function of the beta cells. The complex interplay of such chemical signals is currently being elucidated by ongoing research. But the bottom line is that ultimately, the chronic inflammatory condition and unrelenting action of TNF-α (and likely other pro-inflammatory chemical signals) crashes the system, and diabetes ensues.
So, getting back to the earlier key question, why do the macrophages embedded in the abdominal fat get stirred up in the first place? The answer, in a word, is glycine, or rather, insufficient glycine. Feel free to check out my earlier post (Diet and Inflammation, Part 2) on this blog for the details. But in short, glycine is the body’s most important regulator of inflammation, by keeping membrane channels open for the intake of chloride ions. A constant, low-level influx of chloride is needed to maintain the proper membrane voltage (0.07 volts): If the voltage deteriorates, the cell gets activated. That’s when these macrophages go into action to fight invading microbes. Normally, these cells only get activated when they detect the chemical signature of bacteria or viruses or fungi, but if the concentration of glycine is not high enough, the macrophages get activated to fight microbes that aren’t even there!
Now here’s a key error that the mainstream research and medical world is still laboring under: It is still generally thought that inflammation is also a natural response to tissue injury. I have discovered that–unequivocally—that is not true. When, for example, there is blunt injury—no microbes to kill—macrophages do need to be involved in gobbling up the mess of dead cells and cell debris. But they do not need to get activated, which involves the secretion of destructive chemicals like hydrogen peroxide and TNFα. They only cause damage and delay healing (That’s why it helps to put ice on such a wound, to inhibit inflammation.) And if you are not glycine-deficient, blunt injury does not cause inflammation, but just naturally heals quite quickly.
What about abdominal obesity? After all, there’s not even any tissue injury to activate the macrophages. It is not known what the signal is precisely that sets them off. But I can tell you that they do NOT get activated if glycine is adequate. So where’s the proof of this? Two lines of evidence provide confirmation: First, we find that insulin resistant (pre-diabetic) and type-2 diabetic patients have significantly lower blood levels of glycine than normal. Over the last few years, the evidence for this has been accumulating, thanks in some measure to the new technological advance known as metabolomics, which allows the simultaneous measurement of hundreds of metabolites from each blood sample collected, rather than just a few. So for example, in 2010, a study identified glycine as the single most reduced metabolite—among 485 different metabolites identified—in 143 insulin-resistant 30-60-year-old men and women from 13 European countries, compared to 256 subjects with normal insulin sensitivity. Similar results have been showing up in several other recent studies among subjects with insulin resistance and abdominal obesity, as well as subjects with type 2 diabetes, as had shown up in earlier studies on laboratory rats with diabetes.
Second, clinical trials are starting to show that when insulin resistant and diabetic patients’ diets are supplemented with glycine, the clinical markers of the condition improve markedly as was previously demonstrated in laboratory rats. So, for example, in a study in Mexico City in 2008 found that, in 3 dozen patients taking 15 g/day of glycine (v. placebo controls) mean fasting glucose went down from 183 mg/dL to 140: from way diabetic to right on the border of diabetes. In the same study, hemoglobin A1C (a standard measure of long-term blood sugar control) decreased from 8.3 to 6.9 (i.e., down to non-diabetic levels), and a measure of TNF-α decreased 4-fold! A clinical study of my own is also in the works.
Finally, let’s not underestimate the value of self-experimentation: My experience with my own 8g/day sweetamine supplement was that, with no change in weight, it reduced my fasting glucose–which had gone up over the years to 129; just over the border into diabetic territory–down to 110: the top of the normal range. (Some sweetamine users diagnosed with type 2 diabetes have also reported not needing their medication anymore to control their blood sugar.)
So we end where we began: Enjoy the holidays, and eat, drink and be merry—even if you do pick up a few pounds. Just don’t forget the glycine.
About the Author
Joel Brind, Ph.D. has been a Professor of Biology and Endocrinology at Baruch College of the City University of New York for 28 years and a medical research biochemist since 1981. Long specializing in steroid biosynthesis and metabolism and endocrine-related cancers, he has specialized in amino acid metabolism in recent years, particularly in relation to glycine and one-carbon metabolism. In 2010 he founded Natural Food Science, LLC to make and market glycine supplement products via http://sweetamine.com , which includes his own blog HERE.