JOURNAL OF MEDICINAL FOOD J Med Food XXXX (XX) 1–3 # Mary Ann Liebert, Inc., and Korean Society of Food Science and Nutrition DOI: 10.1089/jmf.2013.0053
SHORT COMMUNICATION
Effect of Fucoidan Administration on Insulin Secretion and Insulin Resistance in Overweight or Obese Adults Diana M. Herna´ndez-Corona,1 Esperanza Martı´nez-Abundis,1 and Manuel Gonza´lez-Ortiz1,2 1
Cardiovascular Research Unit, Department of Physiology, Health Sciences University Center, University of Guadalajara, Guadalajara, Mexico. 2 Medical Research Unit in Clinical Epidemiology, Specialties Hospital, Medical Unit of High Specialty, West National Medical Center, Mexican Institute of Social Security, Guadalajara, Mexico. ABSTRACT The aim of this article is to evaluate the effect of fucoidan administration on insulin secretion and insulin sensitivity in overweight or obese adults. A randomized, double-blind, placebo-controlled clinical trial was carried out in 25 obese or overweight volunteers. Thirteen patients received an oral dose of 500 mg of fucoidan once daily before breakfast and 12 patients received placebo for 3 months. Before and after the intervention, fasting glucose and 2-h postload, total cholesterol, high-density lipoprotein cholesterol, triglycerides, and insulin levels were measured. Low-density lipoprotein cholesterol (LDL-C) and homeostasis model analysis formulas (HOMA) for b-cell function and insulin resistance were calculated. The results showed a significant decrease in diastolic blood pressure (71.7 – 12.2 vs. 67.8 – 13.8 mmHg; P < .05) and LDL-C (3.1 – 0.5 vs. 2.7 – 0.6 mmol/l; P < .01) with increase in insulin levels (60.6 – 24.0 vs. 78.6 – 32.4 pmol/l; P < .05), HOMA b-cell (35.0 – 20.8 vs. 50.6 – 18.7; P < .05) and HOMA IR (1.9 – 1.2 vs. 2.6 – 1.8; P < .05) were observed after fucoidan administration. We conclude that fucoidan administration during a 3-month period in overweight or obese adults decreased diastolic blood pressure and LDL-C concentrations, increasing insulin secretion and insulin resistance. KEY WORDS: fucoidan insulin secretion insulin sensitivity obesity overweight
istration on insulin secretion and insulin resistance in overweight or obese adults.
INTRODUCTION
O
besity is a chronic metabolic disorder caused by an imbalance between energy intake and expenditure and is associated with the extent of adipocyte differentiation, intracellular lipid accumulation, lipolysis, insulin resistance, and compensatory hyperinsulinemia.1 Fucoidan is a sulfated fucose containing polysaccharides extracted from marine brown algae and has recently been recognized to possess biological properties including beneficial effects on lipids along with decrease in weight. Fucoidan inhibits lipid accumulation in 3T3-L1 adipocytes possibly via stimulating lipolysis2 as well as decreasing adipogenesis, which is mediated by the reduction of adipocyte protein 2 (aP2), CCAAR/enhancer-binding protein a and proliferator-activated receptor c (PPARc) mRNA levels.3 The above-mentioned effects of fucoidan may modify insulin secretion and insulin sensitivity. Therefore, the aim of this study was to evaluate the effect of fucoidan admin-
PATIENTS AND METHODS A randomized, double-blind, placebo-controlled clinical trial was carried out in 25 overweight or obese adult volunteers (30 to 60 years of age) (body mass index [BMI] 25– 34.9 kg/m2) with similar demographic and socioeconomic characteristics. All individuals were nonsmokers. Subjects’ weight had remained stable for at least 3 months prior to the study. All subjects denied history of diabetes mellitus, hypertension, and use of any medications known to affect metabolism. None of the subjects were pregnant or breastfeeding. After random allocation of the intervention, 13 patients received an oral dose (500 mg) of F-fucoidan (Green Foods, Swanson Health Products, Fargo, ND, USA) once daily before breakfast and 12 patients received placebo for 3 months. All patients received general recommendations about their medical nutritional therapy and were instructed to not modify their usual exercise habits. Before testing, an isocaloric diet of at least 250 g of carbohydrates/day was given for 3 days. Women were in the first phase of their menstrual cycle (3–8 days). Testing was initiated at 8:00 a.m. after a 12-hour fast. Height and weight
Manuscript received 20 February 2013. Revision accepted 8 January 2014. Address correspondence to: Manuel Gonza´lez-Ortiz, MD, MSc, PhD, Cardiovascular Research Unit, Department of Physiology, Health Sciences University Center, University of Guadalajara, Montes Urales 1409, Col. Independencia 44340, Guadalajara, Mexico, E-mail: [email protected]
1
´ NDEZ-CORONA ET AL. HERNA
2
were measured wearing shoes. Values were used to calculate BMI according to the following formula: weight (kg)/height (m2). Waist circumference was taken at the middle between the highest point of the iliac crest and the lowest rib in the mid-axillary line. Adiposity (% of fat mass) was assessed by bioelectrical impedance analysis using a contact electrode foot-to-foot body fat analyzer system (TBF-300A, Tanita Corporation of America, Arlington Heights, IL, USA). Blood pressure was evaluated by the investigator after a 5 minute resting period with the individual sitting in a chair and determined using a digital sphygmomanometer. Systolic and diastolic blood pressures were based on Korotkoff phases I and V, respectively. Venous blood was obtained with the subject supine in a quiet room. The resulting serum was placed into two aliquots: the first for determination of glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), and the second was frozen at - 20 C for measurement of insulin levels within the following 30 days. Samples of venous blood at 120 minutes after oral administration of 75 g of dextrose were also obtained for glucose determination. Glucose concentration was measured using the glucose– oxidase technique (Ortho-Clinical Diagnostics, Rochester, NY, USA) with an intra- and inter-assay coefficient of variation < 1%. TC, HDL-C, and TG were measured enzymatically. In particular, HDL-C was assessed after selective precipitation of non-HDL-C fractions. Determinations were performed with commercially available equipment (OrthoClinical Diagnostics) with an intra- and inter-assay coefficient of variation of < 3%. Insulin was measured by immunoradiometric assay (CIS Bio International, Gif-Sur Yvette, France) with an intra- and inter-assay coefficient of variation
of 3.8 and 8.0%, respectively. LDL-C was estimated using the Friedewald formula (LDL-C = TC - HDL-C - TG/5). Formulas of the homeostasis model analysis (HOMA) were used to assess insulin resistance and b-cell function (insulin secretion) as follows: insulin resistance (HOMA IR) = fasting insulin (lU/ml) x fasting glucose (mmol/l)/22.5. b-cell function index (HOMA b-cell) = 20 x fasting insulin (lU/ml)/ fasting glucose (mmol/l) - 3.5. If subjects had a fasting glucose < 3.5 mmol/l, they were excluded from the analyses to avoid negative HOMA b-cell function. Sample size was calculated with the formula for clinical trials4 with a 95% confidence level and statistical power of 80%. A standard deviation (SD) of 51.1 with an expected difference of 75.0 was calculated for insulin secretion for a total of eight individuals by group and with insulin resistance the calculation was lower. It was finally decided to include 25 patients due to possible withdrawals. Values are presented as mean – SD. Between-group differences were analyzed by Mann-Whitney U test. Wilcoxon test was used for differences before and after the intervention in the same group. The study was approved by the ethics committee of the participating hospital and fulfilled all requirements for human research. All participants provided written informed consent. RESULTS Three males were included in each group (P = .146). There was no significant difference in age between groups (42.4 – 3.7 vs. 45.4 – 7.3 years, placebo, and fucoidan, respectively; P = .141). Eleven patients from the fucoidan group and eight patients in the placebo group completed the 3-month pharmacological intervention, with a compliance
Table 1. Patient Characteristics Before and After Interventions Placebo
Weight, kg BMI, kg/m2 WC \, cm WC _, cm Adiposity, % Systolic BP, mm/Hg Diastolic BP, mm/Hg Glucose 0’, mmol/l Glucose 120’, mmol/l TC, mmol/l TG, mmol/l HDL-C \, mmol/l HDL-C _, mmol/l LDL-C, mmol/l Insulin, pmol/l HOMA b-cell HOMA IR
Fucoidan
Baseline
3 months
Baseline
3 months
84.6 – 14.1 31.2 – 3.1 97.7 – 7.1 118.0 – 11.0 39.8 – 5.3 119.3 – 12.1 78.2 – 7.7 5.1 – 0.4 5.9 – 0.8 5.2 – 0.6 1.7 – 0.7 1.1 – 0.1 1.1 – 0.2 3.2 – 0.6 87.0 – 40.2 35.0 – 20.8 2.2 – 2.0
91.0 – 11.0 32.9 – 1.9 103.3 – 8.3 111.0 – 9.2 40.0 – 7.1 116.1 – 10.2 78.8 – 7.9 5.1 – 0.3 6.2 – 1.8 5.1 – 0.4 1.8 – 0.7 1.1 – 0.1 1.2 – 0.3 3.1 – 0.5 108 – 60.6 70.6 – 41.4 2.7 – 2.7
75.0 – 6.9 29.9 – 2.4 93.6 – 7.3 102.3 – 6.8 37.6 – 4.6 113.3 – 14.6 71.7 – 12.2 5.0 – 0.5 6.5 – 2.0 5.1 – 0.5 1.6 – 0.6 1.2 – 0.3 1.1 – 0.1 3.1 – 0.5 60.6 – 24.0 35.0 – 20.8 1.9 – 1.2
72.9 – 5.2 29.5 – 2.3 91.5 – 5.0 95.0 – 4.2 36.9 – 4.9 112.4 – 12.9 67.8 – 13.8* 5.1 – 0.7 7.1 – 2.0 4.9 – 0.5 2.1 – 1.7 1.2 – 0.3 1.0 – 0.3 2.7 – 0.6** 78.6 – 32.4* 50.6 – 18.7* 2.6 – 1.8*
*P < .05. **P < .01. BMI, body mass index; WC, waist circumference; BP, blood pressure; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; HOMA, homeostasis model analysis; IR, insulin resistance.
FUCOIDAN ON INSULIN SECRETION AND SENSITIVITY
> 80%. Two patients in the fucoidan group and three patients in the placebo group were considered lost to follow-up. Written informed consent was withdrawn immediately after the first month of treatment in a patient from the placebo group. Statistical analyses were carried out as intention to treat. A significant decrease in diastolic blood pressure and LDL-C with increase in insulin levels, HOMA b-cell, and HOMA IR were observed after fucoidan administration (Table 1). There were no significant adverse events with the administration of fucoidan compared with placebo. Polyphagia was present in three patients from the fucoidan group and in two from the placebo group. Intestinal constipation appeared in two patients from the fucoidan group and in one patient from the placebo group.
3
There is no clear explanation of the beneficial effect of fucoidan on blood pressure along with the decrease of LDL-C levels, and it appears that administration of fucoidan may be a treatment recommendation; however, care must be exercised due to the observed increment in insulin resistance. In conclusion, fucoidan administration during a 3-month period in overweight or obese adults decreased diastolic blood pressure and LDL-C concentrations, increasing insulin secretion and insulin resistance.
ACKNOWLEDGMENT We thank Sharon Morey, Executive Editor, Scientific Communications, for English editorial assistance. AUTHOR DISCLOSURE STATEMENT
DISCUSSION It has been suggested that fucoidan administration may be useful for the prevention or treatment of dyslipidemia and obesity. This may be due to its stimulatory lipolysis effect, which is highly dependent on hormone-sensitive lipase, reducing lipid accumulation.2 Our clinical results in accordance with this fact showed a decrease in LDL-C concentrations, but without effect on weight and adiposity due to the short time of intervention or to the low doses, which may be influencing factors. These factors should be explored in future investigations. Unfortunately, free fatty acid levels were not measured and the real impact of fucoidan in the modification of lipolysis in the studied population is unknown. However, a clinical increment in insulin resistance with compensatory hyperinsulinemia was proven with fucoidan. This fact is supported by in vitro findings that showed suppressed PPARc, CCAAR/enhancer-binding protein a, and aP2.3,5,6 On the other hand, crude fucoidan has been demonstrated to increase insulin sensitivity, decreasing insulin levels and glucose concentration in db/db mice. However, this contradictory effect seems to be dependent on the sulfate content and molecular weight of fucoidan, implicating the CD36-mediated interaction of AGE-modified proteins.3,7 F-fucoidan was used in our study, which has a > 95% composition of sulfated esters of fucose; however, the exact molecular weight was unknown.
The authors state that there is no conflict of interest with regard to this manuscript. The authors declare no competing interests with the mentioned pharmaceutical company. REFERENCES 1. Guilherme A, Virbasius JV, Puri V, Czech MP: Adipocyte dysfunction linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol. 2008;9:367–377. 2. Park MK, Jung U, Roh C: Fucoidan from marine brown algae inhibits lipid accumulation. Mar Drugs. 2011;9:1359–1367. 3. Kim KJ, Yoon KY, Lee BY: Fucoidan regulates blood glucose homeostasis in C57BL/KSJ m + / + db and C57BL/KSJ db/db mice. Fitoterapia. 2012;83:1105–1109. 4. Jeyasselan L, Rao PSS: Methods of determining samples size in clinical trials. Indian Pediatr. 1989;26:115–121. 5. Kim KJ, Lee BY: Fucoidan from the sporophyll of undaria pinnatifida suppresses adipocyte differentiation by inhibition of inflammation-related cytokines in 3T3-L1 cells. Nutr Res. 2012;32:439–447. 6. Kim MJ, Chang UJ, Lee JS: Inhibitory effects of fucoidan in 3T3-L1 adipocyte differentiation. Mar Biotechnol. 2009;11: 557–562. 7. Kuniyasu A, Ohgami N, Hayashi S, Miyazaki A, Horiuchi S, Nakayama H: CD 36-mediated endocytic uptake of advanced glycation end products (AGE) in mouse 3T3-L1 and human subcutaneous adipocytes. FEBS Lett. 2003;537:85–90.
SHORT COMMUNICATION
Effect of Fucoidan Administration on Insulin Secretion and Insulin Resistance in Overweight or Obese Adults Diana M. Herna´ndez-Corona,1 Esperanza Martı´nez-Abundis,1 and Manuel Gonza´lez-Ortiz1,2 1
Cardiovascular Research Unit, Department of Physiology, Health Sciences University Center, University of Guadalajara, Guadalajara, Mexico. 2 Medical Research Unit in Clinical Epidemiology, Specialties Hospital, Medical Unit of High Specialty, West National Medical Center, Mexican Institute of Social Security, Guadalajara, Mexico. ABSTRACT The aim of this article is to evaluate the effect of fucoidan administration on insulin secretion and insulin sensitivity in overweight or obese adults. A randomized, double-blind, placebo-controlled clinical trial was carried out in 25 obese or overweight volunteers. Thirteen patients received an oral dose of 500 mg of fucoidan once daily before breakfast and 12 patients received placebo for 3 months. Before and after the intervention, fasting glucose and 2-h postload, total cholesterol, high-density lipoprotein cholesterol, triglycerides, and insulin levels were measured. Low-density lipoprotein cholesterol (LDL-C) and homeostasis model analysis formulas (HOMA) for b-cell function and insulin resistance were calculated. The results showed a significant decrease in diastolic blood pressure (71.7 – 12.2 vs. 67.8 – 13.8 mmHg; P < .05) and LDL-C (3.1 – 0.5 vs. 2.7 – 0.6 mmol/l; P < .01) with increase in insulin levels (60.6 – 24.0 vs. 78.6 – 32.4 pmol/l; P < .05), HOMA b-cell (35.0 – 20.8 vs. 50.6 – 18.7; P < .05) and HOMA IR (1.9 – 1.2 vs. 2.6 – 1.8; P < .05) were observed after fucoidan administration. We conclude that fucoidan administration during a 3-month period in overweight or obese adults decreased diastolic blood pressure and LDL-C concentrations, increasing insulin secretion and insulin resistance. KEY WORDS: fucoidan insulin secretion insulin sensitivity obesity overweight
istration on insulin secretion and insulin resistance in overweight or obese adults.
INTRODUCTION
O
besity is a chronic metabolic disorder caused by an imbalance between energy intake and expenditure and is associated with the extent of adipocyte differentiation, intracellular lipid accumulation, lipolysis, insulin resistance, and compensatory hyperinsulinemia.1 Fucoidan is a sulfated fucose containing polysaccharides extracted from marine brown algae and has recently been recognized to possess biological properties including beneficial effects on lipids along with decrease in weight. Fucoidan inhibits lipid accumulation in 3T3-L1 adipocytes possibly via stimulating lipolysis2 as well as decreasing adipogenesis, which is mediated by the reduction of adipocyte protein 2 (aP2), CCAAR/enhancer-binding protein a and proliferator-activated receptor c (PPARc) mRNA levels.3 The above-mentioned effects of fucoidan may modify insulin secretion and insulin sensitivity. Therefore, the aim of this study was to evaluate the effect of fucoidan admin-
PATIENTS AND METHODS A randomized, double-blind, placebo-controlled clinical trial was carried out in 25 overweight or obese adult volunteers (30 to 60 years of age) (body mass index [BMI] 25– 34.9 kg/m2) with similar demographic and socioeconomic characteristics. All individuals were nonsmokers. Subjects’ weight had remained stable for at least 3 months prior to the study. All subjects denied history of diabetes mellitus, hypertension, and use of any medications known to affect metabolism. None of the subjects were pregnant or breastfeeding. After random allocation of the intervention, 13 patients received an oral dose (500 mg) of F-fucoidan (Green Foods, Swanson Health Products, Fargo, ND, USA) once daily before breakfast and 12 patients received placebo for 3 months. All patients received general recommendations about their medical nutritional therapy and were instructed to not modify their usual exercise habits. Before testing, an isocaloric diet of at least 250 g of carbohydrates/day was given for 3 days. Women were in the first phase of their menstrual cycle (3–8 days). Testing was initiated at 8:00 a.m. after a 12-hour fast. Height and weight
Manuscript received 20 February 2013. Revision accepted 8 January 2014. Address correspondence to: Manuel Gonza´lez-Ortiz, MD, MSc, PhD, Cardiovascular Research Unit, Department of Physiology, Health Sciences University Center, University of Guadalajara, Montes Urales 1409, Col. Independencia 44340, Guadalajara, Mexico, E-mail: [email protected]
1
´ NDEZ-CORONA ET AL. HERNA
2
were measured wearing shoes. Values were used to calculate BMI according to the following formula: weight (kg)/height (m2). Waist circumference was taken at the middle between the highest point of the iliac crest and the lowest rib in the mid-axillary line. Adiposity (% of fat mass) was assessed by bioelectrical impedance analysis using a contact electrode foot-to-foot body fat analyzer system (TBF-300A, Tanita Corporation of America, Arlington Heights, IL, USA). Blood pressure was evaluated by the investigator after a 5 minute resting period with the individual sitting in a chair and determined using a digital sphygmomanometer. Systolic and diastolic blood pressures were based on Korotkoff phases I and V, respectively. Venous blood was obtained with the subject supine in a quiet room. The resulting serum was placed into two aliquots: the first for determination of glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), and the second was frozen at - 20 C for measurement of insulin levels within the following 30 days. Samples of venous blood at 120 minutes after oral administration of 75 g of dextrose were also obtained for glucose determination. Glucose concentration was measured using the glucose– oxidase technique (Ortho-Clinical Diagnostics, Rochester, NY, USA) with an intra- and inter-assay coefficient of variation < 1%. TC, HDL-C, and TG were measured enzymatically. In particular, HDL-C was assessed after selective precipitation of non-HDL-C fractions. Determinations were performed with commercially available equipment (OrthoClinical Diagnostics) with an intra- and inter-assay coefficient of variation of < 3%. Insulin was measured by immunoradiometric assay (CIS Bio International, Gif-Sur Yvette, France) with an intra- and inter-assay coefficient of variation
of 3.8 and 8.0%, respectively. LDL-C was estimated using the Friedewald formula (LDL-C = TC - HDL-C - TG/5). Formulas of the homeostasis model analysis (HOMA) were used to assess insulin resistance and b-cell function (insulin secretion) as follows: insulin resistance (HOMA IR) = fasting insulin (lU/ml) x fasting glucose (mmol/l)/22.5. b-cell function index (HOMA b-cell) = 20 x fasting insulin (lU/ml)/ fasting glucose (mmol/l) - 3.5. If subjects had a fasting glucose < 3.5 mmol/l, they were excluded from the analyses to avoid negative HOMA b-cell function. Sample size was calculated with the formula for clinical trials4 with a 95% confidence level and statistical power of 80%. A standard deviation (SD) of 51.1 with an expected difference of 75.0 was calculated for insulin secretion for a total of eight individuals by group and with insulin resistance the calculation was lower. It was finally decided to include 25 patients due to possible withdrawals. Values are presented as mean – SD. Between-group differences were analyzed by Mann-Whitney U test. Wilcoxon test was used for differences before and after the intervention in the same group. The study was approved by the ethics committee of the participating hospital and fulfilled all requirements for human research. All participants provided written informed consent. RESULTS Three males were included in each group (P = .146). There was no significant difference in age between groups (42.4 – 3.7 vs. 45.4 – 7.3 years, placebo, and fucoidan, respectively; P = .141). Eleven patients from the fucoidan group and eight patients in the placebo group completed the 3-month pharmacological intervention, with a compliance
Table 1. Patient Characteristics Before and After Interventions Placebo
Weight, kg BMI, kg/m2 WC \, cm WC _, cm Adiposity, % Systolic BP, mm/Hg Diastolic BP, mm/Hg Glucose 0’, mmol/l Glucose 120’, mmol/l TC, mmol/l TG, mmol/l HDL-C \, mmol/l HDL-C _, mmol/l LDL-C, mmol/l Insulin, pmol/l HOMA b-cell HOMA IR
Fucoidan
Baseline
3 months
Baseline
3 months
84.6 – 14.1 31.2 – 3.1 97.7 – 7.1 118.0 – 11.0 39.8 – 5.3 119.3 – 12.1 78.2 – 7.7 5.1 – 0.4 5.9 – 0.8 5.2 – 0.6 1.7 – 0.7 1.1 – 0.1 1.1 – 0.2 3.2 – 0.6 87.0 – 40.2 35.0 – 20.8 2.2 – 2.0
91.0 – 11.0 32.9 – 1.9 103.3 – 8.3 111.0 – 9.2 40.0 – 7.1 116.1 – 10.2 78.8 – 7.9 5.1 – 0.3 6.2 – 1.8 5.1 – 0.4 1.8 – 0.7 1.1 – 0.1 1.2 – 0.3 3.1 – 0.5 108 – 60.6 70.6 – 41.4 2.7 – 2.7
75.0 – 6.9 29.9 – 2.4 93.6 – 7.3 102.3 – 6.8 37.6 – 4.6 113.3 – 14.6 71.7 – 12.2 5.0 – 0.5 6.5 – 2.0 5.1 – 0.5 1.6 – 0.6 1.2 – 0.3 1.1 – 0.1 3.1 – 0.5 60.6 – 24.0 35.0 – 20.8 1.9 – 1.2
72.9 – 5.2 29.5 – 2.3 91.5 – 5.0 95.0 – 4.2 36.9 – 4.9 112.4 – 12.9 67.8 – 13.8* 5.1 – 0.7 7.1 – 2.0 4.9 – 0.5 2.1 – 1.7 1.2 – 0.3 1.0 – 0.3 2.7 – 0.6** 78.6 – 32.4* 50.6 – 18.7* 2.6 – 1.8*
*P < .05. **P < .01. BMI, body mass index; WC, waist circumference; BP, blood pressure; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; HOMA, homeostasis model analysis; IR, insulin resistance.
FUCOIDAN ON INSULIN SECRETION AND SENSITIVITY
> 80%. Two patients in the fucoidan group and three patients in the placebo group were considered lost to follow-up. Written informed consent was withdrawn immediately after the first month of treatment in a patient from the placebo group. Statistical analyses were carried out as intention to treat. A significant decrease in diastolic blood pressure and LDL-C with increase in insulin levels, HOMA b-cell, and HOMA IR were observed after fucoidan administration (Table 1). There were no significant adverse events with the administration of fucoidan compared with placebo. Polyphagia was present in three patients from the fucoidan group and in two from the placebo group. Intestinal constipation appeared in two patients from the fucoidan group and in one patient from the placebo group.
3
There is no clear explanation of the beneficial effect of fucoidan on blood pressure along with the decrease of LDL-C levels, and it appears that administration of fucoidan may be a treatment recommendation; however, care must be exercised due to the observed increment in insulin resistance. In conclusion, fucoidan administration during a 3-month period in overweight or obese adults decreased diastolic blood pressure and LDL-C concentrations, increasing insulin secretion and insulin resistance.
ACKNOWLEDGMENT We thank Sharon Morey, Executive Editor, Scientific Communications, for English editorial assistance. AUTHOR DISCLOSURE STATEMENT
DISCUSSION It has been suggested that fucoidan administration may be useful for the prevention or treatment of dyslipidemia and obesity. This may be due to its stimulatory lipolysis effect, which is highly dependent on hormone-sensitive lipase, reducing lipid accumulation.2 Our clinical results in accordance with this fact showed a decrease in LDL-C concentrations, but without effect on weight and adiposity due to the short time of intervention or to the low doses, which may be influencing factors. These factors should be explored in future investigations. Unfortunately, free fatty acid levels were not measured and the real impact of fucoidan in the modification of lipolysis in the studied population is unknown. However, a clinical increment in insulin resistance with compensatory hyperinsulinemia was proven with fucoidan. This fact is supported by in vitro findings that showed suppressed PPARc, CCAAR/enhancer-binding protein a, and aP2.3,5,6 On the other hand, crude fucoidan has been demonstrated to increase insulin sensitivity, decreasing insulin levels and glucose concentration in db/db mice. However, this contradictory effect seems to be dependent on the sulfate content and molecular weight of fucoidan, implicating the CD36-mediated interaction of AGE-modified proteins.3,7 F-fucoidan was used in our study, which has a > 95% composition of sulfated esters of fucose; however, the exact molecular weight was unknown.
The authors state that there is no conflict of interest with regard to this manuscript. The authors declare no competing interests with the mentioned pharmaceutical company. REFERENCES 1. Guilherme A, Virbasius JV, Puri V, Czech MP: Adipocyte dysfunction linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol. 2008;9:367–377. 2. Park MK, Jung U, Roh C: Fucoidan from marine brown algae inhibits lipid accumulation. Mar Drugs. 2011;9:1359–1367. 3. Kim KJ, Yoon KY, Lee BY: Fucoidan regulates blood glucose homeostasis in C57BL/KSJ m + / + db and C57BL/KSJ db/db mice. Fitoterapia. 2012;83:1105–1109. 4. Jeyasselan L, Rao PSS: Methods of determining samples size in clinical trials. Indian Pediatr. 1989;26:115–121. 5. Kim KJ, Lee BY: Fucoidan from the sporophyll of undaria pinnatifida suppresses adipocyte differentiation by inhibition of inflammation-related cytokines in 3T3-L1 cells. Nutr Res. 2012;32:439–447. 6. Kim MJ, Chang UJ, Lee JS: Inhibitory effects of fucoidan in 3T3-L1 adipocyte differentiation. Mar Biotechnol. 2009;11: 557–562. 7. Kuniyasu A, Ohgami N, Hayashi S, Miyazaki A, Horiuchi S, Nakayama H: CD 36-mediated endocytic uptake of advanced glycation end products (AGE) in mouse 3T3-L1 and human subcutaneous adipocytes. FEBS Lett. 2003;537:85–90.
