HCG Diet Analysis, Part II
“They say: ‘You really need a high level of proof to change the recommendations,’ which is ironic because they never had a high level of proof to set them.”
— Walter Willett, Harvard Professor of Epidemiology & Nutrition
POUNDS & INCHES
The very first paragraph of the Foreword tells us that none of what is coming should be taken as gospel. That its theories and diet recommendations rest only on untested theory and clinical observation, and not tests or clinical trials of any kind:
“This book discusses a new interpretation of the nature of obesity, and while it does not advocate yet another fancy slimming diet it does describe a method of treatment which has grown out of theoretical considerations based on clinical observation.”
Fair enough. Observation over time of a large population can be meaningful. Simeons’ goes on to say:
“What it must do is to give us an intellectually satisfying interpretation of what is happening in the obese body. It must also be able to withstand the onslaught of all
hitherto known clinical facts and furnish a hard background against which the results of treatment can be accurately assessed.”
This is a critical comment, and one by which I believe we should read, interpret and analyze the entire book. Simeons’ not only admits that he is basing all his recommendations on then known clinical (tested) facts, but is open-minded enough to realize that future facts may supersede the information he had available to him at the time. And indeed, in the last sixty years, clinical facts about human metabolism and obesity have changed a lot.
Let’s begin with Simeons’ description of obesity.
“We postulate that obesity in all its many forms is due to an abnormal functioning
of some part of the body and that every ounce of abnormally accumulated fat is always the result of the same disorder of certain regulatory mechanisms. Persons suffering from this particular disorder will get fat regardless of whether they eat excessively, normally or less than normal. A person who is free of the disorder will never get fat, even if he frequently overeats.”
Here he is ahead of his time. He understands that obesity does not obey the flawed illogic of ”Calories In, Calories Out’. That is, it doesn’t matter how much you eat or how little, only what the body does with what you eat: either burn it, or store it. And he understands the decision to burn or store is dependent on this mysterious ‘regulatory mechanism’. This is more knowledge about the true cause of obesity than 99.9% of all practicing doctors have today. Another important point: he is aware that there is no such thing as ‘normal’ fat and ‘abnormal’ fat, only the abnormal accumulation of adipose fat. As we read in Part I, the ability for humans to acquire adipose fat is an adaptive measure that helps our species survive in hard times, and is therefore highly prized by the brain. I’m not sure where the phrase ‘abnormal fat’ began, but it is clear that Simeons is speaking about the abnormal accumulation of adipose fat tissue, and that his goal in the rest of the book and through his diet is to stop further accumulation of it, and to eliminate the excess already there.
“Those in whom the disorder is severe will accumulate fat very rapidly, those in whom it is moderate will gradually increase in weight and those in whom it is mild may be able to keep their excess weight stationary for long periods. In all these cases a loss of weight brought about by dieting, treatments with thyroid, appetite-reducing drugs, laxatives, violent exercise, massage, baths, etc., is only temporary and will be rapidly regained as soon as the reducing regimen is relaxed. The reason is simply that none of these measures corrects the basic disorder.”
We now know that the ‘basic disorder’ is a breakdown of metabolism signaling, leading to abnormal accumulation of adipose fat. It might be leptin, insulin or thyroid hormone resistance, or all three since once one begins it can set off a hormonal cascade that negatively affects the others. Those who are very resistant will indeed gain fat quickly. Those who are mildly resistant will gain fat more slowly. This doesn’t necessarily mean weight gain. You can appear lean on the outside, yet have a large accumulation of adipose fat relative to lean muscle mass. This condition is known as “skinny fat.”
What Dr. S’ doesn’t say however, that needs saying, is the corollary: if you are fat, or getting fat, your metabolism is already broken. In other words, if you are fat, you are insulin and/or leptin resistant to some degree, because as we saw in Part I, the only way to accumulate adipose fat to begin with is if your insulin cell receptors start to reject the glucose carried by insulin. The main question is: how resistant are you? Tests and tools to help you determine that will be in Part III or IV.
We’ll skip over Simeons’ musings about Neanderthals’ eating habits, inheritance of a ‘obesity’ gene, the various glands (thyroid, pituitary, adrenals) that might be causing the ‘basic disorder’ — because over the decades science has proven most of his musings wrong, and in any event he calls all of them a “blind alley.”
It’s at the hypothalamus (or Diencephalon, as he refers to it) that Simeons’ theories truly begin. He states the hypothalamus is: “the part from which the central nervous system controls all the automatic animal functions of the body, such as breathing, the heart beat, digestion, sleep, sex, the urinary system, the autonomous or vegetative nervous system and via the pituitary the whole interplay of the endocrine glands. It was therefore not unreasonable to suppose that the complex operation of storing and issuing fuel to the body might also be controlled by (it).”
He then goes on to infer from this that the hypothalamus contains a “Fat Bank”, about which he states: “Assuming that in man such a center controlling the movement of fat does exist, its function would have to be much like that of a bank. When the body assimilates from the intestinal tract more fuel than it needs at the moment, this surplus is deposited in what may be compared with a current account. Out of this account it can always be withdrawn as required. All normal fat reserves are in such a current account, and it is probable that a diencephalic center manages the deposits and withdrawals. When now, for reasons which will be discussed later, the deposits grow rapidly while small withdrawals
become more frequent” — so far correct — “a point may be reached which goes beyond the diencephalon’s banking capacity.” This last clause is not correct.
And so it is here we need to talk about Aristotle, and what he called “logical fallacies” in On Sophistical Refutations. Simply put, a logical fallacy is a theory or argument (for or against something) based on faulty reasoning. It usually means that the premise of the argument — the underlying assumption — is false. Example: every time you see someone with a wound on their finger they have a band-aid on it. If you assume it is the band-aid that is causing the wound, that’s not only a false premise, it means that all further reasoning based on that premise must also be false. Like then arguing that the elimination of all band-aids from the world will prevent further finger wounds from happening. Or that reducing the number of police officers will reduce violent crime, because you have observed that whenever there is violent crime, police officers are usually present. Or that since high cholesterol raises CHD risk (the false premise), then statins reduce CHD risk in men who already have heart disease because statins lower cholesterol. But although statins do lower cholesterol (an effect), we know now that the risk lowers because statins lower inflammation, the true cause of CHD.
Simeons’ made several of these logical fallacies, where his premise, based on observation but not clinical trials (as with all the examples cited above), was false. This is the first fallacy, though it is not the most important. As we shall see later, the most important observational/logical fallacy he made was about the effect of HCG on adipose fat cells.
LOTS OF LEPTIN
What Simeons’ was actually describing when he outlines his theory of a “Fat Bank” is the protein hormone leptin (Greek leptos meaning thin), even though it wouldn’t be discovered for another forty years. Some call leptin the master metabolic hormone, and I believe this is true although there is still a lot to learn about the many ways it “authorizes” the Burn or Store decision the brain makes for all incoming nutrients. The Ob(Lep) gene (Ob for obese, Lep for leptin) is located on chromosome 7 in humans, and although Simeons’ observed this (or its absence, rather, as we shall see) at work, he did not know of its existence. Later on he would observe the effects of adipose fat release from storage, but attribute the cause of the release to HCG, in part because of not knowing about leptin, but also because the premise upon which he based the attribution also turned out to be false.
Jeffrey M. Friedman and colleagues at the Rockefeller University discovered leptin in 1994, and although it took several years to even begin to understand it, that didn’t stop Big Pharma from jumping for joy, since the discovery (they thought) meant a new gold rush. What they knew about leptin from observation was that it was missing in the hypothalami of morbidly obese mice. And they knew it is the hypothalamus that signals the liver to either ‘turn up the metabolic heat’ (by making more T3 than T4, for example) or to slow it down by making more T4 than T3, or even worse, RT3, which is the metabolic black hole mirror-reverse molecule of T3. Tests showed that leptin injected into these particular mice made them stunningly slim in a very short time. Not just slim by weight, but by inches. These mice lost all their excess adipose fat. They became sleek, positively svelte. Hubba hubba mice.
Thus, the reasoning went, morbidly obese humans (who often weigh hundreds of pounds even at an early age) must also lack sufficient leptin. These are the very people Simeons’ describes in “The Inherited Factor” in which he says: “The fat-banking capacity is abnormally low from birth. Such a congenitally low (hypothalamus) capacity would then represent the inherited factor in obesity. When this abnormal trait is markedly present, obesity will develop at an early age in spite of normal feeding; this could explain why among brothers and sisters eating the same food at the same table some become obese
and others do not.” This was an astute observation from someone who could not possibly know about leptin, but of course a ‘fat-banking capacity’ has nothing to do with it.
Big Pharma went wild, spending millions by 2000 on leptin R&D, looking to find a stabilized form that could be injected. It would cure obesity forever! It would make them billions! One problem. When they ran clinical human trials to test it, it only worked on those who had a chromosome 7 problem. Injecting leptin into those folks produced the same results as it had on the mice: restored leptin signaling. Newly sleek and svelte people stepped out of their fat suits forever.
Aside #1: You would think, given these results, that research scientists and Big Pharma would have immediately slapped their collective foreheads and said: “My bad. All this time we’ve insisted that the cause of obesity is eating too much and exercising too little, that a calorie is a calorie, and that all you need to do to lose weight is have a little willpower and set up a calorie deficit. Gee, that now appears to be a logical fallacy, since our entire premise was false. Turns out it’s not the calories that matter, but what the body does with them, which in turn is based on hormonal signaling. Let’s share this information with the world, and especially the diet book/diet plan/supplement industrial complex so they can stop peddling guilt and useless junk.” As if.
But alas, Big Pharma was riding for a Big Fall. Turns out that folks who are obese but whose chromosome 7 is genetically fine already have sufficient leptin, thank you. Lots and lots of leptin. None of it though is where it belongs, in the hypothalamus, but instead pools uselessly in the bloodstream, unable to cross the blood-brain barrier. Here was a complex medical mystery to be solved, but Big Pharma is only interested in simple medical mysteries that can produce pills or injections, preferably those that need to be taken forever. So they walked out. Literally. Closed their research labs and sold their research to Amylin, the makers of Symlin and Byetta. Amylin is currently in clinical trials for their new combo Symlin/leptin injection, but knowing what I do about leptin, it’s not necessary to use it for the bit of good it may do. I believe leptin signaling can be restored without paying $300 a month for injections, as I hope the experiment outlined below will show.
However, after Big Pharma shut their labs, misinformation, rumors and speculation about leptin and how it works ran rampant for years. New “Leptin Diet” books told you how to Master Leptin. Supplements promised to lower leptin. Hooey. No diet or supplement in the universe will fix a leptin signaling problem, since the cause of the breakdown has nothing whatsoever to do with diet, supplements or food. Those books and the diets based on them (filled with zero clinical trials, even though a simple blood test — taken before this magical diet and after — would let the authors prove they know what they’re talking about) are solely designed to do one thing really well: part you from your money.
Think of leptin as an A1c report to the brain. Just as an A1c blood test tells you what your average blood glucose numbers have been for the last three months (regardless of any one test on any one day), and which tells you how tightly — or not — your insulin has controlled your glucose, leptin levels provide the same type of information about the state of your adipose fat. Every time you eat a meal, your adipose fat cells produce leptin that should reach your hypothalamus, to which it reports. It tells your brain not just what you had for dinner in terms of calories, but also nutrient composition. And it does more. Because it also shows how many adipose fat cells you have, it provides the brain the information it needs to judge how to see you: as a slim person who’s just eaten a lot of food that now needs to be quickly burned and used for energy, or as a starving person with insulin resistance, where no nutrients are reaching the blood cells as fuel. To your brain, this state of deprivation means it will try to conserve every last morsel of the fat-free, low-cal food you just ate as adipose fat. If your brain thinks you’re starving on a desert island, you will continue to store fat until you reach a state of ‘fat stasis,’ where your brain believes you have enough in reserve to keep you alive. Good luck in overcoming the brain’s formidable survival metabolic mechanisms by willpower and a lean cuisine.
This is one of the reasons why a one-thousand-pound person can go into the locked metabolic ward of a hospital, be fed 800 liquid calories a day … and gain half a pound by week’s end. Half a pound of fat, that is, not water. Yes, the composition of the calories matters. Those 800 calories should be composed of 90% saturated fat and 10% protein, but we’re dealing with the medical establishment here, so it’s the usual 20% fat, 30% protein, and 50%
sugar, carbohydrate. And we now know what that person’s insulin resistant muscle cells, and leptin resistant brain will do with that! Do the doctors and researchers then read my Aside #1 and revise their underlying assumptions about what causes obesity? No, they scratch their heads in puzzlement and chalk it up to yet another paradox. The French Paradox. The Spanish Paradox. The Greek Paradox. All these mystifying paradoxes of cultures that eat lots of saturated fat and few sugar carbs (while remaining healthy and slim) surround them, and they still are unwilling to challenge their original clearly errant premise. Maybe we should call this the Stupid Medical Paradox.
“Brain, brain, what is BRAIN?” (Star Trek, TOS, Spock’s Brain)
My own brain is so stupid sometimes I want to slap it. When I look in a mirror, why the heck can’t my brain use my two good eyes to see me as I really am. “Oh, my goodness,” I want it to say. “You’re not a starving waif at all. You’re actually quite the chunky monkey. Alarm! Alarm! Alarm! Get those furnaces going!”
But it can’t do that, because just as insulin resistant cells never get the nutrients meant to fuel them, so the hypothalamus never receives the leptin sent up from your fat! The leptin no longer can cross the Blood-Brain Barrier (BBB). That’s one of the reasons you got fat in the first place.
Here’s how. You eat a meal. Your adipose fat cells produce leptin (the more fat cells, the more leptin you produce; which matters a great deal to your long-term health when you remember how HCG turns “proto”fat cells into full-fledged fat cells), which then heads toward the brain. On the way it meets your Endoplasmic Reticulum (ER – the full description of which is beyond the scope of this blog), which serves many general metabolic functions, including the facilitation of protein folding. Leptin is a protein hormone, and in order to cross the BBB it first folds (with the ER’s help) into a precise three-dimensional shape that fits through the keyhole shaped for it. When the ER becomes “stressed,” which can happen for a wide variety of reasons, including excessively high cortisol levels, leptin does not fold into the proper shape (known as the unfolded protein response, or UPR), and it can not cross the BBB.
Instead it pools in your bloodstream, where it can be measured by a simple blood test. But the ramifications of this pooling are not good. For one, it means that very little leptin is reaching the brain, which no longer has an accurate gauge of how fat you are, how fat you should be, and thus what it should do with the nutrients you just consumed. The signals that decide “burn or store” — the signals that control your entire metabolism — have broken down. Think the “three small meals a day” recommended by a Leptin Diet book are going to fix that?
Is there anything that can fix it? After all, we know that leptin shots (or HCG in any form) won’t work, because what we want is not to artificially lower leptin levels (by consuming 500 calories a day, for instance, which will indeed reduce adipose fat levels — but not be able to inform the brain about it!) but by restoring proper leptin signaling. Without signaling it doesn’t matter what your leptin level is, because your brain can’t ‘see’ it.
Aside #2: I didn’t learn about leptin until after I’d lost a lot of weight, so I got tested. Bad news. Although a truly healthy leptin level is less than 10, mine was 33, higher even than the ‘normal’ range on the lab report. Lab ranges. Useless for accurate interpretation of lab results. For instance, once Big Pharma learned that manipulating ranges meant bigger profit (normal total cholesterol used to be less than 240. But more doctors would prescribe statins if ‘normal’ was redefined as less than 200, so it was), and as doctors moved from treating patients to treating lab numbers, so too did the labs (income dependent on doctors ordering lots of tests) follow suit. Often to ridiculous extremes. I’ve actually seen a new lab level for “normal range” LDL given as 0 – 139. ZERO. Achievable, perhaps, but you’ll be six feet under before you get there.
Sometimes n=1 can be valuable. By the time I got the leptin level news, I had already diagnosed my hypothyroidism as a variant of Wilson’s Temperature Syndrome. I reviewed Wilson’s treatment, found a few flaws, modified the treatment to remove them, applied it, and permanently fixed the problem. Which also, as I had predicted, dropped my total cholesterol (that had been outlier high due to the lack of proper thyroid hormone signaling) like a rock. It went down over 100 points in thirty days. So I wasn’t happy to discover yet another metabolic signaling problem holding me back from reaching my weight goal, despite trying every conceivable diet out there, including Simeons (who knew nothing about leptin, unfortunately). Especially since a review of the medical literature revealed little information on leptin in humans, and no fixes whatsoever. So I dug deeper. Over the next six months I read everything there was to read about leptin and ER signaling problems, and then … Eureka!
There, in Cell Metabolism 9, 35–51, January 7, 2009, was a small article entitled: Endoplasmic Reticulum Stress Plays a Central Role in Development of Leptin Resistance. It described the UPR problem, but better yet: The researchers tried to fix it by using a “chemical chaperone” to accompany the leptin up to the ER, and succeeded. “We show that chemical chaperones … which have the ability to decrease ER stress, act as leptin-sensitizing agents. Taken together, our results may provide the basis for a novel treatment of obesity.” They experimented on very fat mice, and one of those chemicals, TUDCA (tauroursodeoxycholic acid), worked very nicely indeed! The mice lost all their excess adipose fat, kept it off, gained energy and, more importantly, when the researchers harvested the hypothalami, they found that leptin signaling had been fully restored.
Turns out that TUDCA is just taurine-conjugated UDCA in liquid form, which means it can be injected. Mice are notoriously bad at swallowing pills. What’s UDCA? Essentially, bear bile. Although ingesting too much (about a spoonful) will kill a big man in minutes, Native Americans have used the bile from bear livers for hundreds of years as a very potent and life-saving medicine. Non-toxic even in huge doses when made by a lab, it’s on-label use for decades has been to treat cirrhosis of the liver, and now non-alcoholic fatty liver syndrome. But as I discovered, this amazing (cheap, generic) drug is currently in government clinical trials for Parkinson’s Disease and Alzheimer’s — and will likely be tested for many more.
I called the doctor in charge of the trials and asked him about the article. He’d never heard of it, which surprised him since he said he thought he’d read every article about leptin ever written. I told him I wanted to try the experiment on myself. He asked me to send the article first, then we’d talk again. No one he knew had ever tried it for restoring leptin signaling, but he opined that “it shouldn’t kill you.” Great. We worked out a daily amount for me to take based on my weight and on the amount he was using for the Parkinson trials, and I once again talked my trusting Endo into giving me a weird prescription based on yet another of my unorthodox diagnoses (which until this point had always, along with my unorthodox treatments, proven correct), and n=1 began.
Two side-effect-free months later, I took another leptin test. My leptin level had dropped to 22. More than a 30% decrease. I called the doctor back to share the news. He whipped out a science calculator and did some equations, then told me it was statistically impossible for this to be chance. In fact, the drop was statistically significant. He asked me if I would change the experiment to see if leptin signaling had actually been restored, rather than just the level having decreased. So I stopped taking UDCA completely for the next six months. If signaling had been restored my leptin level would decrease again, without the medication, because leptin would now cross the BBB to reach the hypothalamus instead of pooling in my blood stream. The test results after six months were amazing. My LL dropped by another 10%, to 20. And my last test, in January (still with no further UDCA), showed another 10% decrease, to 18. That’s a nearly 50% decrease in leptin levels in one year. I’ve since lost a lot of weight and inches, though in the intervening months I discovered I had one more metabolic hurdle to diagnose and fix: Non-diabetic insulin resistance.
While I realize my n=1 proved nothing, the results were, as the doctor said, significant enough to call my theory (that UDCA would work as well in humans as in mice) a “plausible hypothesis,” which is the first step before writing up a funding grant request, and which, in the hands of real scientists, would probably succeed.
Why does a deep understanding of how leptin and leptin resistance works matter to Fröhlich’s Syndrome, his treatment of those suffering from it, and thus how Dr. Simeons’ came to make his “logical fallacy” about HCG?
On to Part III.