Efecto duradero de un suplemento dietético en fibra para mujeres

(Long-Term Effect of a High Fiber Dietary Supplement on Total Body Weight, Fecal Fat, Lipid Profile and Blood Pressure in Female Human Subjects)

Por: Lori Nesbitt, PHD, Carlos M. Ricart, MS, PHD, Jorge Miranda-Massari, Pharmd and Michael J. González, DSC, PHD, FACN

(Bio Medicina
The journal of the HispanoAmerican Biomedical Association
Vol. 2 No. 8 October, pages s9-s12)

Summary

A mixed-fiber dietary supplement, Fattaché, containing chitosan, pectin, psyllium and glucomannan, was studied to determine its efficacy on dietary fat binding and weigh loss in a double-blind, placebo-controlled trial. Fecal fat content, body weight, blood pressure and lipid profiles were evaluated before and after 30 days of treatment with the mixed fiber supplement. Following the double-blind period, all patients received active treatment, in an-open fashion, for 60 additional days. The patient population consisted of 37 mildly-to-moderately obese, otherwise healthy, volunteers. After only 4 weeks of treatment, the mixed fiber supplement had a statistically significant (p<0.0001, u = 0.005) positive weight reducing effect (-3.63 vs. + 2.34). This weight reduction was associated with a corresponding statistically significant (p<0.0002, u = 0.005) increase in fecal fat content in the treatment groups (+2.48%) vs. the placebo (-3.73%). In addition, decreases in total cholesterol, LDL-cholesterol and increases in HDL-cholesterol were obtained. These positive results lead us to conclude that Fattaché is a safe and effective mixed fiber supplement for dietary fat binding and weight loss. The lipid profile finding suggests benefits of Fattaché as a natural occurring lipid-lowering agent irrespective of its weight loss potential.

Obesity is a major public health concern because it increases morbidity, mortality, psychological problems, discrimination and reduces economic achievement. It is etiology is variable and of a very complex metabolic and physiologic nature. Obesity can be defined as an excess of adipose tissue or the excessive accumulation of body fat. This accumulation of excessive fat is the primary culprit of obesity's harmful effects. Americans and Puerto Ricans consume about two times as much fat as is considered appropriate (40% vs. 20%), in addition to consuming the wrong types of fat (saturated, trans-fatty acid and excessive Omega 6 fatty acids). The increasing obesity problem in combination with smoking habits, and minimal or absent physical activity accompanied by a high fat intake, are a truly deadly combination that has been linked to cardiovascular morbidity and mortality, and to certain types of cancer (breast, colon, prostate).

There is a great need for physiological research to help define and describe effective adipose tissue loss that may suppress, appetite, inhibit or block lipid absorption, and/or increase thermogenesis. Of great interest is the use of supplements and nutriceutical products to help create a proper environment or provide a fine metabolic tuning that will facilitate weight/fat reduction goals. For this purpose supplements containing fibers (chitin, chitosan, pectin, glucomannan and psyllium) have been used.

Recently, the use of a modified diet and adjunctive drug therapy have been used to achieve desirable reductions in body weight and lipid levels. To date, prescription drug therapy has been restricted to severe hypercholesterolemia due to safety concerns, inherent to long-term drug therapy. Thus, positive weight and lipid profile results derived from the combination of aerobic exercise, low fat diet, and supplementation has gained scientific and public interest. Supplementation with naturally-ocurring fibers such as chitosan, psyllium, pectin, glucomannan and guar gum are readily available and commonly recommended by physicians and nutritionist to treat mild to moderate hypercholesterolemia.

Chitin is a fibrous material found in the exoskeleton of crustaceans. Chemically, chitin is a polymer primarily formed by repeating units of n-acetylglucosamine with a structure similar to to cellulose. Chitin when heated is converted to chitosan, a polysaccharide, formed mainly of repeating units of D-glucosamine, which have a positive charge. At acidic pH, the amino acid groups take on hydrogen ions resulting in an overall positive charge to the polymer. Due to this positive charge, negatively charged molecules can be attached to these sites and be ionically bound to chitosan. Examples of negatively charge molecules include free fatty acids and bile acids, among other. Chitosan when bound to negative-charge molecules can be excreted out of the body in the feces.

Various animal studies demonstrated an increased lipid excretion and reduced fat digestibility when given chitosan. Nevertheless, despite these interesting results in animal studies, human studies are scarce. To our Knowledge, only one study with human subjects using chitosan has been reported in the scientific literature. This was a short-term pilot study designed to monitor safety and to measure fecal fat content and body weight before and after a mixed fiber supplement (Fattache) was given to normal healthy volunteers. Also, blood pressure and fasting lipid profiles were measured as secondary endpoints. The trends resulting from this short-term study with Fattaché were very encouraging. An increased fecal fat, lower body weight, lower LDL, higher HDL, lower triglycerides and lower systolic blood pressure resulted.

This long-term study was designed to measure the effect of a mixed-fiber dietary supplement (Fattaché) on body weight, fecal fat, blood pressure and lipid profile over a longer period of time. In addition, we wanted to determine long-term safety and efficacy.

Methods

This double blind, placebo-controlled study was conducted in 37 female subjects who were mildly-to-moderately overweight (5% to 15% above average body weight) but otherwise healthy. Eighteen patients received a placebo and 19 patients received treatment with 500-mg capsules of a mixed fiber supplement (Fattaché) for an initial 30-day period. Fattaché is a mixed-fiber supplement containing 51% psyllium, 40% chitosan, 4% glucomannan and 4% pectin. Following the initial double-blind period, all patients received treatment with Fattaché for an additional 60 days in an open-label fashion.

Eligible patients meeting all inclusion criteria were consented and then randomized to treatment or placebo groups. Baseline measurements of fecal fat, body weight, blood pressure and serum lipids were obtained. As a safety measure, a complete blood count, urinalysis were performed to check for long-term safety and efficacy.

All subjects were dispensed Fattaché or placebo (first 30 days only) at regular intervals and instructed to take four capsules twice daily. The participants were also asked to drink 8 to 10 8-oz. glasses of water daily and to continue their normal dietary habits (with no calorie reduction or any type of weight-reduction regimen). Daily dietary food charts were completed by each patient. Compliance with all study-related procedures was strictly monitored.

In order to be enrolled in the study, the patients had to be female, 18 to 70 years of age, sign a written informed consent, and be 5% to 15% above average body weight for gender, height and body type. Eligibility weight percentiles were based on the 1993 metropolitan height-weight tables. Patients were excluded from the study if they were pregnant or breast feeding, had a history of any disabling disease or chronic condition or had an allergy to shellfish or pectin-containing products.

Eligibility for study entry was assessed by the principal investigator after a complete medical history and physical examination was completed by a physician. Safety labs, including a complete blood count, urinalysis and urine pregnancy test were obtained.

Baseline (Study day 1): Prior to initiation of Fattaché supplementation, a full fasting lipid profile and a 72-hour stool sample for a quantitative measure of fecal fat were collected. Routine vital signs were measured and recorded. A seven-day supply of Fattache or placebo was dispensed.

Study Days 1 through 90: Throughout the entire study, patients were instructed to take 4 capsules of Fattache with the AM meal and 4 capsules with the PM meal. Each dose was to be taken with an 8-oz. glass of water. Patients were also urged to drink 8 to 10-8oz. glasses of water and complete daily food charts. Concomitant medications and adverse events were recorded.

Study Days 7 and 14: Patients were asked to return to the clinic for routine vital signs, to check for compliance and food chart completion, and Fattache was again dispensed. All non-compliant patients were withdrawn from the study at this time. Compliance was checked by counting remaining capsules of Fattache and by completion of food charts.

Study Day 30 or Early Termination: Patients returned to the clinic for a final double-blind study visit. A physical exam was completed by a physician. A second fasting lipid profile and safety labs were obtained. A 72-hour stool sample for quantitative fecal fat determination was collected. Routine vital signs, including body weight, were measured and recorded. Patients returned all completed food charts and any unused Fattaché capsules. A 30-day supply of open-label Fattaché was dispensed to all patients.

Study Days 60 and 90: Patients returned to the clinic for open- label visits. A physical exam was completed by a physician. A fasting lipid profile and safety labs were obtained. Routine vital signs, including body weight, were measured and recorded. Patients returned all completed food charts and unused Fattaché capsules.

This study was designed to have 20 patients per treatment group complete a 30-day double-blind period followed by an additional 60 days of open-label treatment of the study and again on days 30 (double-blind period), 60, and 90 (open-label period) . The variables were: body weight, percent fecal fat, HDL (high-density lipoprotein), LDL (low –density lipoprotein), total cholesterol and blood pressure (systolic and diastolic)

Double-Blind Period: For each of the seven variables, a one sample t-test was used to check for statistical significance from baseline within the placebo group and within the Fattaché group. A two sample t-test was used to check for statistical significance between the placebo and Fattaché groups. The t-test assumes normal distribution of data. In order to verify normal distribution each variable was assessed by a normal Q-Q plot and a Kolmogorov-Smirnov Goodness of Fit test, and a normal distribution was obtained for each of them.

Sixty and 90-day data were collected for each variable except percent fecal fat, and change from baseline was analyzed (Day 60 – baseline). The statistical analyses used in the double-blind period were also utilized in the open-label part: however, only half the group (control) received placebo for the first 30 days, and patients were randomized using a randomization code. Fattaché and placebo capsules were packaged identically. Then patients were crossed-over to supplementation with Fattaché. Thus, by day 90 this group had received 30 days of placebo and 60 days of Fattaché; the Fattaché group received all 90 days of active treatment. In addition, a within-subject ANOVA (repeated measures) was done with Greenhouse-Geisser (CG) and Huynh-Feldt (H-F) adjustments.

Results

Body weight was measured twice during the double-blind period, once at the beginning of the study (baseline) and a second time at 4 weeks (30 days) of treatment with Fattaché or placebo. The average weight loss for the Fattaché group was 3.63 lb., while placebo group gained and average of 2.34 lb. A statistically significant difference between the Fattaché and placebo group was obtained (p<0.0001).

For the open-label study, body weight was measured at baseline (at the end of the double-blind period, on day 60, and on day 90). Patients in the placebo group experienced an average initial weight gain of 2.34 lb. After being switched over to Fattaché, these patients lost an average of 2.14 lb. after 30 days of Fattaché suplementation (60 days total in the study). After 60 days of Fattaché (90 days total in study), the ex-placebo group lost an average of 2.06 lb. The average weight loss for the experimental (Fattaché supplemental group) was of 3.63 lb. after 30 days, 5.65 lb. after 60 days, and 5.42 lb. after 90 days. A statistically significant difference was confirmed between the initial experimental and initial control group (p<0.01 at 60 days, and p<0.033 at 90 days).

Stool samples were collected twice during the double-blind period, once at the beginning of the study and a second time after 30 days of treatment with Fattaché or placebo. The amount of fat in each 72-hour stool sample was determined and percent fat was calculated. The supplemental group experienced an average 2.48% increase in fecal fat content, while the placebo group had an average decrease of 3.73% in fecal fat. Fattaché significantly increased percent fecal fat when compared to placebo (p>0.0002). There was no open-label period for fecal fat content.

Total cholesterol was measured twice during the double-blind period, once at the beginning of the study and a second time after 30 days of treatment with fiber supplement or placebo. The Fattaché group experienced an average decrease of 11.05 mg/dl in total cholesterol while the placebo group had an average increase of 20.17 mg/dl. Fattaché very significantly decreased total cholesterol compared to placebo in this study (p<0.0001).

For the open-label part, total cholesterol was measured at baseline, at the end of the double-blind period, on day 60, and on day 90. Patients who where given placebo for the first 30 days experienced an average increase of 20.17 mg/dl. After being crossed-over to Fattaché, those patients had a decrease of 21.42 mg/dl after 30 days supplementation (60 days total in the study). After 60 days of Fattaché (90 days total in the study), these patients had a decrease in total cholesterol of 35.03 mg/dl. The average change in total cholesterol from baseline for the group supplemented with Fattaché for the total study was a decrease of 11.05 mg/dl after 30 days, a decrease of 12.33 mg/dl after 60 days, and a decrease of 4.64 mg/dl after 90 days. A statistically significant difference between the two groups was detected at 30 days (p<0.0001). No statistical difference was obtained thereafter.

LDLs were collected twice during the double-blind period, once at the beginning of the study and a second time after 30 days of treatment with either Fattaché or placebo. The LDLs in the Fttaché supplemented group decreased by an average of 11.72 mg/dl. The LDLs of the placebo group increased by an average of 14.21 mg/dl. In this study, Fattaché significantly decreased low-ensity lipoproteins compared to placebo (p<0.0001).

For the open-label part, LDLs were measured at baseline, at the end of the double-blind period, on day 60, and on day 90. Patients who were treated with placebo for the first 30 days experienced an average increase in LDLs of 14.21 mg/dl. After being crossed-over to Fattaché, these patients hada a decrease of 2.77 mg/dl (60 days total in the study). After 60 days of supplementation (90 days total in the study), these patients had a decrease in LDL of 9.01 mg/dl. The average change in LDLs from baseline of the group supplemented in both double-blind and open period was a decrease of 11.72 mg/dl after 30 days, a decrease of 14.92 after 60 days, and a decrease of 15.30 after 90 days. A statistically significant difference was obtained between the experimental and control groups for day 30 (p<0.0001) and on day 60 (p<0.0003).

HDLs were collected twice during the double-blind period, once at the beginning of the study and a second time after 30 days of treatment with Fattaché or placebo. The HDLs in the Fattaché group increased by an average of 4.95 mg/dl while the HDLs in the placebo group decreased by an average of 4.61 mg/dl. In this study, Fattaché significantly increased high-density lipoproteins compared to placebo (p<0.0001).

For the open-label study, high-density lipoproteins (HDLs) were measured at baseline at the end of the double-blind on day 60 and on day 90. Patients who were treated with placebo for the first 30 days experinced an average decrease in HDLs of 4.61 mg/dl. After being crossed-over to Fattaché, these patients had an increase of 5.44 mg/dl following 30 days of Fattaché (60 days total in the study). After 60 days of Fattaché(90 days total in the study), these patients had an increase in HDLs from baseline for the group supplemented with mixed fibers throughout the study was an increase of 4.95 mg/dl after 30 days, an increase of 2.62 mg/dl after 60 days, and an increase of 4.40 mg/dl after 90 days. A statistically difference was obtained between the two groups (Experimental Vs Placebo) after 30 days (p<0.0001), but no statistical difference was obtained for days 60 and 90.

Systolic blood pressure was measured twice during the double-blind period, once at the beginning of the study and a second time after 30 days of treatment with Fattaché or placebo. The Fattaché – supplemented group experienced an average decrease of 2.71 mm Hg after 30 days, while the placebo-treated group experienced an average decrease in systolic blood pressure of 1.94 mm Hg. Nevertheless, a significant difference was detected (p<0.01).

In the open-label part, systolic blood pressure were measured at baseline, at the end of the double-blind periods, on day 60, and on day 90. Patients who were given placebo for the first 30 days experienced an average minimal decrease in systolic blood pressure of 1.94 mm Hg. After being crossed-over to Fattaché, these patients had a negligible increase in systolic blood pressure after 30 days of Fattaché (60 days total in the study). After 60 days of supplement (90 days total in the study), they had a decrease in systolic blood pressure of 2.35 mm Hg. The average change in systolic blood pressure from baseline in the continually-supplemented group was a decrease of 2.71 mm Hg after 30 days, a decrease of 2.27 mm Hg after 60 days., and a decrease of 6.78 mm Hg after 90 days. A statistically significant difference was detected between the supplemented and placebo group at day 30 only (p<0.01).

Diastolic blood pressure was measured twice during the double-blind period, once at the beginning of the study and a second time after 30 days of treatment with Fattaché or placebo. The Fattaché supplemented group experienced an average decrease in diastolic blood pressure of 5.35 mm Hg after 30 days while the placebo group experienced an average decrease in diastolic blood pressure of 6.65 mm Hg. A statistical difference was not detected.

For the open-label study, diastolic blood pressures were measured at baseline, at the end of the double-blind period, on day 60 and on day 90. Patients who were treated with placebo for the first 30 days experienced an average decrease in diastolic blood pressure of 6.65 mm Hg. After being crossed-over to Fattaché, these patients had a decrease in diastolic blood pressure of 3.56 mm Hg after 30 days of Fattaché (60 days total in the study). After 60 days of supplementation (90 days total in the study) they had a slight average increase in diastolic blood pressure of 4.51 mm Hg. The average change in diastolic blood pressure from baseline in the group supplemented throughout the entire study was a decrease of 5.35 mm Hg. after 30 days, a decrease of 4-45 mm Hg after 90 days. No statistical difference was detected between the supplemented and placebo group.

At each visit, patients were asked if they experienced any side effects or adverse events. Only two patients experienced adverse events. One patient complained of headache, diarrhea, bloating and gas while supplemented with Fattaché. This was described as mild and was determined to be possibly due to Fattaché. Both symptoms were completely resolved when Fattaché was discontinued. A rash was noticed on the second patient. However, this patient was on placebo when the rash developed: thus, this adverse event was not related to Fattaché. It is likely that this fiver supplement will decrease the absorption of vitamins and minerals in order to avoid this inconvenience when using this supplement long-term; vitamin and mineral supplements should be taken 2-3 hours prior to Fattaché supplementation. In genral, this mixed fiber supplement an be considerd safe if taken in the doses used in this study.

Twenty-two out of 37 patients took at least 90% of the study supplement, 31 of 37 patients took at least 80%, 35 of 37 took at least 70%, while 2 patients had compliance of 53% and 68%. Percent compliance was verified by counting remaining pills in the returned containers.

As in the pilot study, the main reason why the study supplement was not taken was missed meals; patients elected not to take the supplement when a rare morning or evening meal was skipped. The patient that was only 53% compliant, was randomized to the Fattaché group, gained 1.5 lb. after 30 days, the dropped out of the study. However, the patient that was only 68% compliant lost 6 lb. after 90 days of treatment with Fattaché. Lastly, only 21 out of 37 patients completed the entire 90 days of treatment.

Discussion

This clinical investigation of a mixed fiber supplement (Fattaché) was undertaken because to date data available on safety and effectiveness of a mixed fiber supplement on human weight reduction and lipid profile are lacking. Animal data exists suggesting an important role for fibers such as chitosan, psyllium, pecting and glucommanan in the treatment of obesity.

The investigation was a double-blind, placebo-controlled study followed by an open-label, sixty-day extension period. This study was follow-up clinical trail to a previously conducted open-label pilot study by our group. The primary aims were to idenfify differences in total body weight, fecal fat content, blood pressure, and serum lipid concentrations by comparing the mixed fiber supplement to a placebo group. Our secondary aims were to define the longer-term (60-90 days) safety profile and efficacy of this mixed fiber supplement on weight loss, blood pressure and lipid profile.

Fattaché also clearly lowered total cholesterol after 30 days (11.05 mg/dl), but over time this change from baseline became smaller (4.64 mg/dl at day 90). The total cholesterol-lowering effects of Fattaché were replicated in both groups as well as in the pilot study. Thus, for cholesterol-lowering effects alone this mixed-fiber supplement might be an attractive alternative therapy.

Fattaché consistently lowered LDL levels during the 90-day study. The effectiveness of Fattaché in lowering LDLs was achieved after the first 30 days on the supplement. For HDLs, Fattaché significantly increased levels at day 30 when compared to the placebo group (4.61 mg/dl for placebo vs. 4.95 mg/dl for Fattaché). Of interests is that Fattaché increased HDLs significantly in both treatment groups, the ones receiving Fattaché throughout the entire study and the ones that crossed-over after 30 days on placebo.

For blood pressure values, both placebo and Fattaché groups had small changes from baseline for the 30-60 and 90-day measurements. Although there was a statistically significant difference between the placebo and experimented groups at day 30, this difference was small in biological terms. There were no highly relevant changes in blood pressure for either group in any measurements. While the pilot study suggested a blood pressure-lowering trend, this trend did not hold in this long-term study.

Patients found the dietary mixed fiber supplement (Fattaché) easy to take and experienced practically no adverse side effects such as insomnia, headaches and irritability often found in other dietary supplements and aids.

This mixed fiber supplement containing chitosan, pectin, glucomannan and psyllium (Fattaché seems to be a safe, non-addicting and effective dietary supplement for weight, fat and cholesterol reduction. Interestingly, these effects have been irrespective of diet and exercise in middly-to-moderately obese patients. A large double blind 90-day outpatient study in a morbidly obese patient population seems a logical follow-up to these exciting results.

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