Body Composition & Bone Density
Body composition was determined using a calibrated Hologic 4500W dual-energy x-ray absorptiometry (Bedford, MA) with the Hologic version V7, Rev F software (Waltham, MA). The dual-energy x-ray absorptiometry (DEXA) segments regions of the body (right arm, left arm, trunk, right leg, and left leg) into three compartments for determination of fat, soft tissue (muscle), and bone mass. The scanned bone, fat, and fat-free/soft tissue mass for each region were subtotaled to determine whole body values. Percent body fat was calculated by dividing the amount of measured fat mass by total scanned mass. Day-to-day reliability studies of hip, spine, and whole body scans on men and women show the DEXA used in this study to be a highly reliable and precise method for determining variations in body composition segments . Test-retest reliability studies performed on male and athletes with this DEXA machine yielded a mean deviation for total BMC and total fat free/soft tissue mass of 0.31% with a mean intra-class correlation of 0.985 . Quality control (QC) calibration procedures were performed on a spine phantom (Hologic X-CALIBER Model DPA/QPR-1 anthropometric spine phantom) prior to each testing session. In addition, weekly calibration procedures were performed on a density step calibration phantom. Testing was performed by certified radiology technicians who properly positioned the subjects in a supine manner on the DEXA table and executed testing according to standard procedures.
Subjects observed an overnight eight  hour fast prior to reporting to the lab to donate blood. Approximately 6 teaspoons of venous blood (30 milliliters) were obtained through venipuncture of an antecubital vein in the forearm using standard phlebotomy procedures. Samples were collected into one (1) 10 mL Vacutainer SST™ gel and clot activator tube, and two (2) 5 mL Vacutainer Brand K3 EDTA™ sterile interior tubes. Trained laboratory technicians centrifuged the blood samples at 5000 rev × min-1 for 10 minutes in a Biofuge 17R Centrifuge (Heraeus Inc., Germany). Serum from one SST tube was transferred into Costar microcentrifuge tubes (Corning Incorporated, Corning, NY) using plastic disposable Falcon™ transfer pipets (Becton Dickinson) and frozen at -80° Celsius for subsequent analysis. Serum from the remaining SST and EDTA tubes were transferred into two (2) separate 10 mL plain sterile tubes. The whole blood was diluted with 2 mL of saline solution. Both serum and whole blood samples were refrigerated and sent to Quest Diagnostic Labs (Ann Arbor, MI) for clinical analysis.
A complete 31-panel clinical chemistry profile was run on serum samples using the Technicon DAX model 96-0147 automated chemistry analyzer (Technicon Inc., Terry Town, NY) following standard clinical procedures. This panel consisted of muscle enzymes [creatine kinase, phosphorus, calcium]; liver enzymes [direct bilirubin, total bilirubin, gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase, AST (SGOT), ALT (SGPT)]; lipid profile [triglycerides, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), cholesterol/HDLC ratio, glucose], electrolytes [sodium, potassium, chloride, carbon dioxide, urea nitrogen (BUN), creatinine, BUN/creatinine ratio], protein status [uric acid, total protein, albumin, globulin, albumin/globulin ratio], and whole blood cell counts [hemoglobin, hematocrit, red blood cell counts, white blood cell counts (basophils, absolute basophils, eosinophils, absolute eosinophils, monocytes, absolute monocytes, lymphocytes, absolute lymphocytes, neutrophils, absolute neutrophils), platelet count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW)]. Cell counts with percent differentials were run on whole blood samples using a Coulter STKS automated analyzer (Coulter Inc., Hialeah, FL) using standard procedures.
Frozen serum samples were sent to the Department of Physiology at East Tennessee State University to assay thyroid stimulating hormone (thyrotropin), thyroxin, total thyroxin, and fasting insulin. A chemistry profile was run on these samples using an Immulite Mark 5 HSS chemiluminescence random access immunoassay analyzer (Diagnostic Products Corporation, Los Angeles, CA) following standard procedures. These analyzers were calibrated daily to controls according to manufacturer recommendations and federal guidelines for clinical diagnostic laboratories. Test to test reliability of performing these assays ranged from 2 to 6% for individual assays with a average variation of ± 3%. Samples were run in duplicate to verify results if the observed values were outside control values and/or clinical norms according to standard procedures . Analysis of these blood parameters helped determine the safety effects of this nutritional supplementation formulation on general markers of clinical health status and selected hormones.
Sisyphus and his endless task
My BMI is 21, but my e-mail and Facebook accounts must think I’m fat. I am constantly bombarded with messages about miracle weight loss solutions, and most of them are diet supplements featured on the Dr. Oz show. Back in December I wrote an article about Garcinia cambogia, Dr. Oz’s “newest, fastest fat buster.” I made this prediction: “I confidently expect another “miracle” to supplant Garcinia in the Land of Oz in the not-too-distant future.” I was right. The e-mails about Garcinia have recently been outnumbered by e-mails about a new Dr. Oz miracle weight loss supplement, forskolin. Actually, I think he discovered forskolin before he discovered Garcinia, but the forskolin propaganda seems to have reached a critical mass in the last few weeks.
The Land of Oz
A Dr. Oz episode on the “Rapid Belly Melt” aired a month ago, on May 5. He set fire to a paper representation of a fat belly to show how forskolin “works like a furnace inside your body.” The paper ignited, went up in flames, and revealed a non-flammable model of muscle tissue inside to show how forskolin burns fat, not muscle, and to illustrate how quickly it works.
In an earlier episode, in January, he called forskolin “lightning in a bottle,” and a “miracle flower to fight fat.” His guest, a weight loss expert, claimed it had doubled the weight loss of her clients. She said “if your metabolism is sleeping, forskolin is gonna wake it up.” She doesn’t claim that it will work miracles all by itself, but recommends it as an addition to gentle exercise and “cleaning up the diet”.
Dr. Oz says he pulled up all the research and was impressed by the evidence that it “ignites your metabolism.” He illustrates this metaphorically by throwing a white powder into a pot of simmering water, causing it to instantly start boiling vigorously.
The Land of Evidence
Dr. Oz is easy to impress. He cites a randomized placebo-controlled double blind trial of forskolin. It was a small preliminary study of obese or overweight men; there were only 15 men in each group, and the study lasted for 12 weeks. The subjects on forskolin showed favorable changes in body composition: a significant decrease in body fat percentage and fat mass, with a trend (non-significant) toward increased bone mass and lean body mass. Serum free testosterone levels were also significantly increased.
The details of the study are not important. What’s important is that the subjects taking forskolin did not lose weight. Even without weight loss, the changes in body composition are likely beneficial, but the increase in testosterone could be dangerous. Whatever the unresolved questions about benefits and risks, it is obviously misleading to cite this study as evidence that forskolin has been proven to melt belly fat or improve weight loss.
Another double blind study of 23 mildly overweight women, showed that forskolin had no significant effects on body composition and concluded that it “does not appear to promote weight loss but may help mitigate weight gain in overweight females with apparently no clinical significant side effects.”
Those are the only two studies in humans. Supplement Geek has written an analysis of some of the flaws in those studies that I won’t get into here. The only other pertinent research I could find was a study in rats suggesting that it may be effective in preventing diet-induced obesity. In rats.
What is it?
Forskolin is an herbal extract from Coleus forskohlii, a plant belonging to the mint family. Its mechanism of action? It increases the production of cyclic AMP, which increases the contractility of heart muscle. Evidence for other actions is preliminary and inconclusive: there is speculation that it may have effects in other cells of the body such as platelet and thyroid cells, it may prevent platelet aggregation and adhesions, and it might even prevent tumor cell growth and cancer metastasis. So far, there is no evidence that it is clinically useful or safe for those purposes.
The Natural Medicines Comprehensive Database rates forskolin as “possibly effective” as an inhaled powder for asthma, and as an intravenous medication for idiopathic congestive cardiomyopathy. It also mentions that it may decrease intraocular pressure but has not been tested in patients with glaucoma. It doesn’t even mention the possibility of using it for weight loss. The safety rating is “possibly safe,” and it lists potential interactions with prescription drugs and with other herbs and supplements. They say it may increase the risk of bleeding and should be discontinued at least 2 weeks before surgery.
The bottom line
So what do we know?
- There is a more-or-less plausible mechanism of action, as speculated by the study authors (see the study for details).
- It improved body composition in one study but not in another.
- It has not been demonstrated to cause weight loss, except possibly in rodents.
- Its clinical efficacy and safety have not been established.
- It raises blood levels of testosterone, probably not a good thing.
I am not saying it doesn’t work for weight loss or belly melting; we don’t have good enough evidence to know whether it does or not. I’m not saying people shouldn’t take it, although they shouldn’t assume it’s perfectly safe. I’m only saying there is inadequate evidence for anyone to make the claims Dr. Oz and other proponents have made for it. If we had such limited evidence for a proposed new prescription drug, I doubt if Dr. Oz would want the FDA to approve it for marketing. The double standard is obvious.
Déjà vu all over again
I’m getting really tired of these weight-loss products, ever since I wrote about Akavar 20/50 “Eat all you want and still lose weight!” back in January 2008. I get a strong stink of déjà vu, because they all fit the same pattern: a small grain of plausibility, inadequate research, exaggerated claims, and commercial exploitation. There are always testimonials from people who lost weight, probably because their will to believe in the product encouraged them to try harder to eat less and exercise. But enthusiasms and fads don’t last. A year later, the same people are likely to be on a new bandwagon for a different product. Dr. Oz will never lack for new ideas to bolster his ratings. Enthusiasm for easy solutions and for the next new hope will never flag as long as humans remain human. I guess I’ll just have to keep doing the Sisyphus thing and hope that I can at least help a few people learn to be more skeptical and to question what the evidence really shows.