Life Extension Magazine June 2009
Physician’s Guide: Using Blood Test Findings To Safely Induce Weight Loss
By William Faloon
By William Faloon
The prevalence of obesity has doubled since the year 1980. The latest study reveals that for the first time, obese Americans outnumber those who are merely overweight.
The war against obesity is an obvious failure. Overlooked are a plethora of research findings indicating substantial fat-loss effects in response to the proper use of bioidentical hormones, certain prescription drugs, and nutrients, along with lifestyle changes.
The reason these proven weight-loss strategies have not caught on is that when used in isolation, they often fail to meet the expectations of a typical obese or overweight individual.
In this eye-opening report, Life Extension® discusses how to interpret blood test results to prescribe an armada of medications, natural hormones, and lifestyle alterations that can safely induce substantial and sustainable weight loss.
Our Bloated Bloodstreams
Overeating is associated with bloating of the gastrointestinal tract (stomach and intestines). Forgotten is what happens after excess fats and sugars leave the digestive system and enter the bloodstream.
People in modern societies have succumbed to a pathological propensity of ingesting excess calories throughout the day (and sometime night). The result of successive meal intakes is that our bloodstreams are chronically bloated with fats and sugars. Constant exposure to excess fats and sugars results in insulin resistance,1-3 oxidative stress,4,5 vascular inflammation,1,5-9 and platelet activation,10 all of which sharply increase heart attack,1,2,6,11,12 stroke,6 and diabetes12,13 risks. Chronically bloated bloodstreams also contribute to unwanted weight gain and preclude the shedding of surplus fat pounds.
The term postprandial is defined as “after eating a meal.” A growing number of medical studies discuss the role of postprandial lipemia (too much fat remaining in the blood after a meal) and postprandial hyperglycemia (too much after-meal glucose) as culprits in today’s obesity epidemic. As long as our meals contain enough of the wrong fats, a transient increase in postprandial lipemia will likely occur. Even when simple carbohydrates are avoided, insulin resistance causes many aging people to suffer higher-than-desirable blood glucose and correspondingly elevated triglyceride levels.14,15
Unless definitive actions are taken, most people will spend most of the day in a postprandial state, i.e., their bloodstreams will be chronically overloaded with sugars and fats. One might think that dieting (food restriction) alone would resolve postprandial metabolic disorders. The problem is that there are fundamental age-related impediments that often require pharmaceutical intervention to circumvent.
Dietary Sugars or Fats—There May be Little Difference
Postprandial metabolic disorders can be caused by chronically eating the wrong kinds of fats or simple carbohydrates. For overweight individuals, it may not matter which food groups they choose to restrict. That is because as the blood becomes saturated with fats or sugars, enzymatic conversions of fat to glucose and vice versa results in chronic postprandial overload that can sabotage the best-laid weight-loss plan.
Most of us are familiar with how delayed or excess insulin secretion (postprandial hyperinsulinemia) contributes to weight gain. Consuming soluble fibers before each meal can help normalize insulin responses and the release of dietary carbohydrates into the bloodstream. Correcting the postprandial disorders afflicting overweight and obese individuals, however, often requires more aggressive intervention.
Please know that patients with normal fasting glucose and triglyceride blood levels can nonetheless suffer from excess postprandial fat (triglyceride) and sugar (glucose), meaning their bloodstreams remain bloated two to eight hours after eating.
Temporarily Suppressing Fat and Carbohydrate Enzymes
In recognizing postprandial disorders as an under-lying cause of weight gain and impediment to successful fat loss, we will review studies showing benefits when lipase, alpha-glucosidase, or alpha-amylase enzymes are inhibited in the digestive tract.
For some patients, drugs or nutrients that inhibit these enzymes will cause gastrointestinal discomforts. The objective of suggesting these enzyme inhibitors on a 60-90-day trial basis is to provide the patient with an opportunity to restore a healthier metabolic profile, provide immediate fat-loss effects (especially in the abdomen), and forcibly educate the patient about the life-long dietary patterns they should endeavor to follow.
The temporary use of compounds that inhibit fat and sugar absorption is designed to “break” the “food addiction” cycle that causes so many people to be overweight or obese. For example, if one’s diet consists of more than 30% calories from fat, a lipase inhibitor drug (orlistat) will induce unpleasant gastrointestinal side effects and provide strong motivation for the patient to make healthier food choices.16
Treating Postprandial Disorders
It is difficult to initiate weight loss in the presence of a bloodstream that is chronically overloaded with glucose and lipids. While each patient will express individual variability, implementing a treatment regimen to reduce the postprandial burden will facilitate an improvement in metabolic parameters that helps reduce body fat, while lowering markers of vascular disease risk.
Patients of course should be encouraged to initiate diets low in saturated and omega-6 fats, while consuming complex whole-food carbohydrates and soluble and insoluble fibers, along with foods that naturally contain omega-3 fatty acids. While following a Mediterranean-type diet is considered ideal, overweight patients in the real world will most often require additional interventions to ameliorate postprandial disorders that have developed over a period of years or decades.
The four steps for reversing postprandial overload are:
Inhibiting the Alpha-Glucosidase Enzyme
The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular diseases that appear outwardly in the form of visceral obesity.
Postprandial hyperglycemia is one characteristic feature of insulin resistance. Excess blood glucose rapidly converts into triglycerides and other lipids and impairs fat clearance with the result being postprandial lipemia.17 Excessive postprandial absorption of glucose has been associated with greater cardiovascular disease risk than the fasting plasma glucose level.18,19
Aggressive actions to suppress postprandial hyperglycemia are thus an important first step in reducing excess body fat and protecting against vascular disease.
Before carbohydrates are absorbed from food, they must be broken down into smaller sugar particles like glucose by enzymes in the small intestine. One of the enzymes involved in breaking down carbohydrates is called alpha-glucosidase. By inhibiting this enzyme, simple carbohydrates (like sucrose) are not broken down as efficiently and glucose absorption is delayed. Alpha-glucosidase inhibitors are available as prescription drugs (such as acarbose) or dietary supplements (such as the InSea2™ compound contained in the new Enhanced Irvingia formula). They function by decreasing the breakdown of simple carbohydrates in the intestine, resulting in a slower and lower rise in blood glucose throughout the day, especially after meals.
Alpha-glucosidase inhibitors are sometimes used in the treatment of type 2 diabetes, but their use has also been studied in non-diabetic individuals. A multicenter, placebo-controlled randomized trial revealed that the alpha-glucosidase inhibitor drug acarbose improved postprandial hyperglycemia and reduced the risk of development of type 2 diabetes in patients with impaired glucose tolerance. In this study, acarbose treatment was also found to slow the progression of intima-media thickness of the carotid arteries, a surrogate marker for atherosclerosis, and reduce the incidence of cardiovascular diseases and newly diagnosed hypertension. This study also showed that acarbose produced small reductions in body mass index and waist circumference.20
A meta-analysis of seven long-term studies has also shown that intervention with acarbose prevents heart attack and cardiovascular diseases in type 2 diabetic patients. This analysis showed improvements in glucose control, triglyceride levels, body weight, and systolic blood pressure in response to acarbose treatment.21
How Effective Are Alpha-Glucosidase Inhibitors?
An overview of the published literature on alpha-glucosidase inhibitors reveals the following:
It is regrettable that the medical establishment has largely ignored the multiple benefits demonstrated by alpha-glucosidase inhibitors in published clinical trials. One study showed a 91% reduction in acute heart attack incidence in response to acarbose therapy in patients with impaired glucose tolerance.22 A meta-analysis showed a 36% decreased incidence of type 2 diabetes in patients taking acarbose.23
You would think these kinds of studies would make headline news, but pharmaceutical companies have not promoted these findings the way they do for statin drugs. One reason may be that the public can access low-cost alpha-glucosidase inhibitors as over-the-counter dietary supplements.
The weight loss shown in response to alpha-glucosidase inhibitors is considerably less than what one might expect. While one report showed 15.4-pound weight loss over five months in single case study, most clinical studies show weight loss of only a few pounds.23 Based on these reports, alpha-glucosidase inhibitors (like acarbose) should not be used as standalone methods for inducing weight loss. Alpha-glucosidase inhibitors have been documented to effectively ameliorate postprandial conditions24,25 and would appear to be an important initial constituent in a comprehensive weight-loss program.
When one observes how effective alpha-glucosidase inhibitors are at reducing blood glucose levels, yet only minimally effective at inducing weight loss, it becomes apparent that a multi-pronged approach (as will be described herein) is required to successfully combat obesity.
Additional Benefits Using Alpha-Amylase Inhibitors
Carbohydrates contribute to the synthesis of fats in our bodies. Since postprandial hyperglycemia leads to an increase in fat storage, the use of substances that interfere with glucose breakdown and absorption are important components of a weight-loss program.
As just discussed, alpha-glucosidase inhibitors interfere with the breakdown of simple carbohydrates into glucose. Alpha-amylase inhibitors, on the other hand, interfere with the breakdown of large carbohydrate molecules like starch into linked glucose polymers. These simple sugars are then broken down to glucose by the alpha-glucosidase enzyme.
The best-documented alpha-amylase inhibitor consists of an extract from the white kidney bean (Phaseolus vulgaris). In a placebo-controlled study, those taking standardized white kidney bean extract lost 3.8 pounds over an eight-week period. More importantly, they lost 1.5 inches of abdominal fat and their triglycerides plummeted 26 points (milligrams per deciliter, or mg/dL), indicating a reduction of the deleterious postprandial syndrome.26
There would appear to be an even greater benefit in combating postprandial hyperglycemia-lipemia by taking both an alpha-glucosidase and an alpha-amylase inhibitor. Such combinations are now available in dietary supplement form. Alternatively, one can be prescribed 50 mg three times a day of the drug acarbose, while a standardized white kidney bean extract supplement can be taken before each carbohydrate-containing meal. Specific dosing suggestions will appear in the summary on "page 3 Tying All This Together".
Any patient with a fasting triglyceride blood level over 80 mg/dL should be suspected as suffering some degree of postprandial lipemia. As is too often observed, overweight patients usually present with fasting triglyceride readings well over 150 mg/dL, which indicates postprandial hyperglycemia and lipemia as underlying causes of their weight gain. Inhibiting carbohydrate absorption will help reduce triglyceride and glucose blood levels.
Please remember that alpha-glucosidase and alpha-amylase enzyme inhibition is only one step in the comprehensive weight-loss program we are presenting.
Inhibiting the Lipase Enzyme
A regrettable consequence of normal aging is that people no longer have the metabolic capacity to consume the same number of calories they did in their youth. Part of this loss of metabolic capacity relates to the aging patient’s increasing inability to rapidly utilize and then purge dietary fats from their bloodstream.
Excess calorie intakes manifest outwardly as unwanted fat deposition. The vascular and inflammatory damage inflicted by chronic overeating, however, can be as deadly as when a smoker diagnosed with emphysema continues to smoke. For some smokers, no matter how many respiratory and vascular diseases they contract, they continue their tobacco habit until the very day it kills them.
We fear “food addiction” may be an even greater problem for aging humans based on startling studies that began appearing only a few years ago. These studies show heart attack and stroke risks to be substantially higher in patients with only modestly elevated after-meal (postprandial) triglyceride levels.27 Coupled with data revealing how obesity is related to chronically elevated blood fat levels (lipemia), it is critical to take aggressive steps to reduce the amount of fats that linger in patients’ bloodstreams.
The sidebar below (Ensure Adequate Absorption of Fat-Soluble Nutrients in Orlistat Patients) provides a number of proven methods to reduce postprandial lipemia. For overweight and obese patients seeking to lose substantial body fat, however, we are recommending a 60-90-day regimen using a lipase inhibitor drug called orlistat.
Orlistat reduces dietary fat absorption by 30% and has been around for about 10 years.28,29 It functions by blocking an enzyme (lipase) that breaks down dietary fat in the intestinal tract, thus impeding its absorption into the bloodstream.
Clinical studies demonstrate significant weight loss in response to using this drug.30,31 In the real world, however, orlistat has been associated with gastro-intestinal discomforts including fat-laden diarrhea and fat seepage into patients’ underwear, causing patients to discontinue its use.
We at Life Extension® are concerned with potential side effects that could manifest in response to long-term use of a drug like orlistat. We are more frightened, however, about the inability of obese individuals to lose enough weight to regain youthful metabolic function. We therefore recommend that patients commit to taking orlistat for 60-90 days. It will dramatically reduce postprandial lipemia.
If patients consume too many fat calories, they will likely suffer digestive discomforts that should force them to adopt healthier eating patterns that they should follow for the rest of their lives. We also believe that the visual appearance of fat in an obese patient’s feces, combined with the knowledge that absorption of this fat results in deadly postprandial lipemia and continued weight gain will motivate life-long reduced fat ingestion.
One might think that if overweight and obese individuals took 120 mg of orlistat before each meal (which would reduce absorption of dietary fats by 30%), significant weight loss would universally occur. The harsh reality is that study subjects had to reduce their dietary fat intake and take orlistat. This documents the futility of relying on modest dieting alone to significantly reduce body fat. It reveals that people are consuming far more calories than they should be, resulting in chronically bloated bloodstreams that preclude successful weight loss.
How Orlistat Works
Orlistat is an inhibitor of pancreatic and gastric lipase. It decreases the intestinal absorption of ingested dietary triglycerides by 30%.37
By reducing postprandial lipemia, orlistat enhances weight loss, lessens insulin resistance, and improves cardiovascular risk factors in patients with metabolic syndrome, with and without type 2 diabetes.38
In studies of obese subjects, orlistat treatment improves insulin and glucose blood levels while significantly decreasing C-reactive protein, a marker of chronic inflammation.39-41 Orlistat treatment favorably influences other blood markers (such as leptin and adiponectin) that are involved with obesity.40
Short-term (10 days) use of orlistat reduced daytime lipemia (triglyceridemia) by 17% in obese, non-diabetic women with metabolic syndrome, with only minimal side effects.42
In a one-year trial of overweight women, a group with metabolic syndrome treated with orlistat (120 mg three times a day) and lifestyle modification lost 20.5 lbs compared with only 0.44 lbs weight loss in the placebo control group.43 A group of overweight women without metabolic syndrome taking the same dose of orlistat + lifestyle modification lost 20.2 lbs more than the control group with metabolic syndrome.43
In a three-month open-label trial of overweight patients without type 2 diabetes treated with orlistat (120 mg three times a day), men lost 17.4 lbs and women lost 12.3 lbs.42 In overweight patients with type 2 diabetes mellitus, men lost 18.7 lbs and women lost 12.5 lbs.44 In overweight patients without type 2 diabetes mellitus, the level of insulin resistance as measured by HOMA-IR (a validated modeling instrument for insulin resistance), decreased by 28% with orlistat treatment.44 For overweight patients with type 2 diabetes mellitus, insulin resistance decreased by 41%. Leptin levels decreased by 51% in men with type 2 diabetes and 29% in women with type 2 diabetes mellitus. Leptin levels dropped by 49% in overweight men and 28% in overweight women without type 2 diabetes mellitus.44 A reduction in leptin blood levels is considered a favorable response as it indicates a reduction in the “leptin resistance” phenomenon that so often precludes weight loss.
Not all studies, however, demonstrate this much weight loss in response to orlistat. Poor compliance is always a factor in the variability that exists among studies of the same compound. Another reason for these discrepancies is that orlistat users are warned to avoid excess ingestion of dietary fats, and are likely to switch to consuming more simple carbohydrates. Overweight individuals often suffer metabolic disturbances, meaning that ingested sugars readily convert to stored (triglyceride) fats on the body. This is why taking carbohydrate-blocking agents (alpha-gluco-sidase and alpha-amylase inhibitors) in conjunction with orlistat for the first 60-90 days may be necessary to induce some of the immediate reduction of fat pounds that overweight and obese individuals expect.
In conjunction with the medications, dietary alterations, supplements, and lifestyle changes discussed in this article, the use of orlistat for a 60-90-day initiation period should provide some immediate weight loss, while enabling the re-establishment of a more youthful metabolic profile in the body whereby postprandial lipemia, insulin resistance, and other metabolic abnormalities are suppressed.
Orlistat is available by prescription in 120 mg capsules as Xenical®, or over-the-counter under the trade name alli® in 60 mg capsules. The suggested dose for the 60-day initiation period is 120 mg before each meal (three times a day). Considering the relatively high cost of over-the-counter alli®, patients with insurance coverage might save money by using prescription-strength orlistat.