Globin Digest: No Evidence for a Weight Loss Mechanism

Frank Greenway,Andrew Roberts,Catherine Parker,Irene Grundy,Lilian de Jonge-Levitan,Marlene Most,James Ferguson 한국식품영양과학회 2006 Journal of medicinal food Vol.9 No.4

This study was designed to document the mechanism through which globin digest, a dietary herbal supple-ment, might cause weight loss by exploring possible fat malabsorption, calorie malabsorption, energy expenditure, and fat ox-idation. Six healthy subjects were placed on an outpatient diet for 14 days and given a meal containing 40.9 g of fat on days5 and 11, and stools were collected for 72 hours after each meal for analysis of fecal fat content. Four grams of globin digestwas given with one meal and placebo with the other. In another separate study, six subjects were placed on a 100-g fat, weight-maintaining diet for 14 days. All food was prepared by the Pennington Center (Baton Rouge, LA) metabolic kitchen. Globindigest (2 g) or placebo was given with each of three meals per day, and stool was collected for calorie determinations duringthe last 72 hours of each week. Subjects received globin digest during one of the 2 weeks and placebo during the other. Rest-ing metabolic rate and respiratory quotient were measured on the last day of each 1-week period. There was no increase in72-hour fecal fat or fecal calories by bomb calorimetry during either of the studies. There was no difference in the respira-tory quotient. Globin digest did result in an increase in resting metabolic rate. However, this increase was not statistically sig-nificant. Globin digest, if effective, does not cause weight loss or fat loss through fat malabsorption or a relative increase infat oxidation. Future studies are needed to document the efficacy of globin digest for weight loss in humans before furthermechanistic investigation is attempted.

Fourteen Weeks of Treatment with Viscofiber Increased Fasting Levels of Glucagon-Like Peptide-1 and Peptide-YY

Frank Greenway,Carol E. O'Neil,Laura Stewart,Jennifer Rood,Michael Keenan,Roy Martin 한국식품영양과학회 2007 Journal of medicinal food Vol.10 No.4

Fermentable dietary fiber has been shown to cause fat loss and to increase peptide-YY (PYY) and glucagon-like peptide 1 (GLP-1) levels in rodents. In single meal tests, humans have an increase in PYY and GLP-1 to dietary fiber,but the response of these hormones to longer-term treatment is not known. Viscofiber?? (Cevena Bioproducts Inc., Edmonton,AB, Canada) is a high-viscosity fermentable dietary fiber made by a proprietary process from oats and barley. Seven healthyoverweight and obese subjects were treated with a calorie-restricted diet, a lifestyle change program, and 4 g of Viscofiber/dayfor 16 weeks. Hunger, satiety, PYY, and GLP-1 were measured before and 1 hour after a standard meal test before and atweek 14 of the study. Hunger and satiety were measured by Visual Analog Scales. PYY and GLP-1 were measured by ra-dioimmunoassay and enzyme-linked immunosorbent assay, respectively. Weight was reduced 3.07. 3.13 kg (P. .05) overthe 16 weeks. Fasting PYY increased 8.67. 6.62 pg/mL (P. .05) and fasting GLP-1 increased 2.67. 0.84 pmol/L (P..01) at 14 weeks compared to baseline. Satiety increased 1.78. 1.43 cm (P. .01) at the 1-hour post-meal time point onweek 14 compared to the study baseline. We conclude that 14 weeks of treatment with Viscofiber at 4 g/day along with alifestyle change program and diet causes weight loss and increases fasting PYY, fasting GLP-1, and satiety at 1 hour fol-lowing a standard meal, which extends the single meal test observations in humans.

The Safety and Efficacy of a Dietary Herbal Supplement and Gallic Acid for Weight Loss

Frank L. Greenway,Andrew T. Roberts,Corby K. Martin,Zhijun Liu,Ronald J. Amen,Eugene A. Woltering,Jennifer C. Rood,Mary K. Caruso,Ying Yu,Hui Xie 한국식품영양과학회 2007 Journal of medicinal food Vol.10 No.1

The objective of this study was to test the safety and efficacy of NT, a dietary herbal supplement made fromrhubarb, ginger, astragulus, red sage, and turmeric, combined with gallic acid (GA) to reduce food intake and cause weightloss. A total of 105 healthy subjects, 1860 years old with a body mass index of 2535 kg/m2 and on no chronic medication,were randomized to a 300 mg/1.2 g NT-GA combination, a 600 mg/2.4 g NT-GA combination, or placebo in three divideddoses daily for 24 weeks. Food intake was measured at baseline and 2 weeks, and safety parameters were followed regularly.Pharmacokinetic studies of a 200 mg/800 mg NT-GA combination and 800 g GA alone were performed with and withoutfood. There was no dose-related weight loss or reduction in food intake at the 8-week analysis, and the study was terminatedearly. Pharmacokinetic studies showed plasma levels of GA did not increase above 10 .M and were not dose-related. TheNT-GA at all concentrations was well tolerated, but was ineffective in causing weight loss or in suppressing food intake. Phar-macokinetics suggested that GA plasma levels were limited by oral absorption, and may be the reason for lack of efficacy.

Dietary Herbal Supplements with Phenylephrine for Weight Loss

Frank Greenway,Lilian de Jonge-Levitan,Corby?artin,Andrew Roberts,Irene Grundy,Catherine Parker 한국식품영양과학회 2006 Journal of medicinal food Vol.9 No.4

This study was designed to evaluate the efficacy and safety of a dietary herbal supplement containing citrusaurantium and phenylephrine in the treatment of obesity. Two pilot studies enrolled healthy subjects with body mass indexes2540 kg/m2 to similar 8-week weight loss programs. Safety was assessed by physical examination and laboratory tests atscreening and 8 weeks. The first pilot study randomized eight subjects to citrus aurantium (herbal phenylephrine) or placebo.Body composition by DEXA scan, waist circumference, and resting metabolic rate (RMR) were measured at baseline and 8weeks. Food intake and appetite ratings were measured at baseline and week 2. The second pilot study randomized 20 sub-jects to two 2-hour RMR tests a week apart after phenylephrine (20 mg) or placebo followed by phenylephrine (20 mg) threetimes a day for 8 weeks. In the first pilot study, the citrus aurantium group gained 1.13. 0.27 (mean. SEM) kg comparedwith 0.09. 0.28 kg in the placebo group (P. .04). RMR at baseline rose more in the citrus aurantium group, 144.5. 15.7kcal/24 hours, than the placebo group, 23.8. 28.3 kcal/24 hours (P. .002), but not at 8 weeks. DEXA, waist circumfer-ence, food intake, and hunger ratings were not different. In the second pilot study, the phenylephrine group lost 0.8. 3.4 kgin 8 weeks (not significant), and RMR increased more in the phenylephrine group (111.5. 32.6 vs. 37.4. 22.7 kcal/24hours, P. .02). There were no significant safety issues in either study. Although no toxicity was seen, these pilot studiessuggest phenylephrine is not efficacious for weight loss.

The Effects of Grapefruit on Weight and Insulin Resistance: Relationship to the Metabolic Syndrome

Ken Fujioka,Frank Greenway,Judy Sheard,Yu Ying 한국식품영양과학회 2006 Journal of medicinal food Vol.9 No.1

To study the effects of grapefruit and grapefruit products on body weight and metabolic syndrome, 91 obesepatients were randomized to either placebo capsules and 7 ounces (207 mL) of apple juice, grapefruit capsules with 7 ounces(207 mL) of apple juice, 8 ounces (237 mL) of grapefruit juice with placebo capsule, or half of a fresh grapefruit with aplacebo capsule three times a day before each meal. Metabolic syndrome parameters were measured at the beginning and endof 12 weeks. After 12 weeks, the fresh grapefruit group had lost 1.6 kg, the grapefruit juice group had lost 1.5 kg, the grape-fruit capsule group had lost 1.1 kg, and the placebo group had lost 0.3 kg. The fresh grapefruit group lost significantly moreweight than the placebo group (P. .05). A secondary analysis of those with the metabolic syndrome in the four treatmentgroups demonstrated a significantly greater weight loss in the grapefruit, grapefruit capsule, and grapefruit juice groups com-pared with placebo (P. .02). There was also a significant reduction in 2-hour post-glucose insulin level in the grapefruitgroup compared with placebo. Half of a fresh grapefruit eaten before meals was associated with significant weight loss. Inmetabolic syndrome patients the effect was also seen with grapefruit products. Insulin resistance was improved with freshgrapefruit. Although the mechanism of this weight loss is unknown it would appear reasonable to include grapefruit in aweight reduction diet.

Low-Energy Dense Potato- and Bean-Based Diets Reduce Body Weight and Insulin Resistance: A Randomized, Feeding, Equivalence Trial

Candida J. Rebello,Robbie A. Beyl,Frank L. Greenway,Kelly C. Atteberry,Kristin K. Hoddy,John P. Kirwan 한국식품영양과학회 2022 Journal of medicinal food Vol.25 No.12

We evaluated the effect of diets low in energy density (1 kcal/g) and high in either potatoes (Potato) or pulses (Bean) on blood glucose control in participants with insulin resistance. We hypothesized that the Potato and Bean diets would have equivalent effects. This was an 8-week randomized, parallel design, controlled feeding study comparing Potato and Bean diets (50–55% carbohydrate, 30–35% fat, 15–20% protein). Equivalence was prespecified as the mean change in the blood glucose concentration for Potato that was within ±20% of the Bean diet. Thirty-six participants (age: 18–60 years, body mass index: 25–40 kg/m2) with insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] >2) were enrolled. Body weight was measured, and subjects underwent a mixed meal tolerance test at baseline and after 8 weeks. Intent-to-treat (ITT) and completer analyses were conducted. Equivalence between the two diets in the area under the curve for serum glucose was attained within ±10%, but the reduction from baseline was not statistically significant. For the Bean diet, insulin (area under the response curve: −2136.3 ± 955.5 mg/[dL∙min], P = .03) and HOMA-IR (−1.4 ± 0.6, P = .02) were lower compared with baseline. ITT and completer analyses were similar, except that HOMA-IR was also reduced by the Potato diet (−1.3 ± 0.6, P < .05). Compliance with the diets was 87–88%, and body weight was reduced in both diets (Potato: −5.6% ± 0.6%; Bean: −4.1% ± 0.6%, P < .001) with no significant difference between the two diets. Potato and Bean diets low in energy density were equally effective in reducing insulin resistance and promoting weight loss in individuals with impaired blood glucose control. Clinical Trial: The trial was registered with ClinicalTrials.gov Identifier: NCT04203238.

Sodium Propionate or Sodium Butyrate Promotes Fatty Acid Oxidation in HepG2 Cells Under Oxidative Stress

Kristina J. Cook,Ann Coulter,Michael Keenan,Frank Greenway,Jack N. Losso 한국식품영양과학회 2023 Journal of medicinal food Vol.26 No.1

The beneficial effects of sodium butyrate (NaB) and sodium propionate (NaP) on fatty acid oxidation (FAO) genes and production of proinflammatory cytokines related to nonalcoholic fatty liver disease (NAFLD) were evaluated using HepG2 human liver hepatocellular carcinoma cells exposed to palmitate/oleate or lipopolysaccharides (LPSs) as a model. The results showed that NaP or NaB was able to promote FAO, regulate lipolysis, and reduce reactive oxygen species production by significantly increasing the mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), adipose triglyceride lipase (ATGL), carnitine palmitoyltransferase 1 alpha (CPT1α), fibroblast growth factor 21 (FGF21), and uncoupling protein 2 (UCP2) in HepG2 cells. Together, NaP and NaB may produce greater effects by increasing CPT1α, PPARα, and UCP2 mRNA expression in LPS-treated HepG2 cells and by increasing CPT1α and ATGL mRNA expression in palmitate-/oleate-treated HepG2 cells. Only NaP treatment significantly increased FGF21 mRNA expression in palmitate-/oleate-treated HepG2 cells. The enzyme-linked immunosorbent assay results revealed that only pretreatment with LPSs and not palmitate/oleate significantly increased tumor necrosis factor alpha (TNF-α) expression in HepG2 cells. NaP alone or in combination with NaB significantly decreased TNF-α expression in LPS-induced HepG2 cells. The expression of interleukin-8 in both models showed no significant differences in all treatments. NaP and NaB show potential for in vivo studies on NAFLD.

Naringenin Increases Insulin Sensitivity and Metabolic Rate: A Case Study

Navya Murugesan,Kaylee Woodard,Rahul Ramaraju,Frank L. Greenway,Ann A. Coulter,Candida J. Rebello 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.3

Our studies in primary human adipocytes show that naringenin, a citrus flavonoid, increases oxygen consumption rate and gene expression of uncoupling protein 1 (UCP1), glucose transporter type 4, and carnitine palmitoyltransferase 1β (CPT1β). We investigated the safety of naringenin, its effects on metabolic rate, and blood glucose and insulin responses in a single female subject with diabetes. The subject ingested 150 mg naringenin from an extract of whole oranges standardized to 28% naringenin three times/day for 8 weeks, and maintained her usual food intake. Body weight, resting metabolic rate, respiratory quotient, and blood chemistry panel including glucose, insulin, and safety markers were measured at baseline and after 8 weeks. Adverse events were evaluated every 2 weeks. We also examined the involvement of peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ (PPARγ), protein kinase A (PKA), and protein kinase G (PKG) in the response of human adipocytes to naringenin treatment. Compared to baseline, the body weight decreased by 2.3 kg. The metabolic rate peaked at 3.5% above baseline at 1 h, but there was no change in the respiratory quotient. Compared to baseline, insulin decreased by 18%, but the change in glucose was not clinically significant. Other blood safety markers were within their reference ranges, and there were no adverse events. UCP1 and CPT1β mRNA expression was reduced by inhibitors of PPARα and PPARγ, but there was no effect of PKA or PKG inhibition. We conclude that naringenin supplementation is safe in humans, reduces body weight and insulin resistance, and increases metabolic rate by PPARα and PPARγ activation. The effects of naringenin on energy expenditure and insulin sensitivity warrant investigation in a randomized controlled clinical trial.

Mechanism for the Increase in Human Growth Hormone with Administration of a Novel Test Supplement and Results Indicating Improved Physical Fitness and Sleep Efficiency

Amy L. Heaton,Colleen Kelly,Jennifer Rood,Charmaine S. Tam,Frank L. Greenway 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.6

An oral test supplement increases serum human growth hormone (hGH) levels after acute administration in healthy adults. We investigated the mechanism for the increase in hGH and the effect of continued daily administration of the test supplement on measures of physical fitness and sleep efficiency. In Study 1, serum triiodothyronine (T3) was measured in samples from a prior placebo-controlled, double-blind study in which 16 healthy participants received both placebo and the test supplement in a crossover design; treatment order was randomized, and treatments were separated by a 1-week washout. In Study 2, physical fitness (VO2 max) was measured at baseline and after 2 weeks of daily administration of the test supplement (N = 12 healthy participants). Study 3 assessed daily sleep onset latency and time awake during 3 weeks of daily administration of the test supplement (N = 15 healthy participants). A fall from baseline in T3 was observed with placebo (−6.1 ± 8.5 ng/dL, P = .01). Of note, the change in T3 was smaller with the test supplement (−3.3 ± 10.7 ng/dL, P = not significant) but was not statistically different from placebo. Mean VO2 max increased by 6% from baseline after 2 weeks (P = .02). Sleep-onset latency and time awake during the night were reduced from baseline to week 3 by 22% and 65%, respectively (P = .01 and P = .02). The conservation of T3 levels suggests that the mechanism for increased hGH secretion by the test supplement is through somatostatin inhibition. Furthermore, pilot studies indicated that daily administration of the supplement improved physical fitness and sleep efficiency from baseline, effects consistent with increased endogenous hGH release.

Fenugreek Bread: A Treatment for Diabetes Mellitus

Jack N. Losso,Darryl L. Holliday,John W. Finley,Roy J. Martin,Jennifer C. Rood,Ying Yu,Frank L. Greenway 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.5

Use of fenugreek, a food with demonstrated efficacy in lowering blood sugar, is limited by its bitter taste and strong flavor. A bread incorporating fenugreek using a proprietary process was tested for its taste acceptability and its effect on carbohydrate metabolism. We developed a fenugreek bread formula that was produced in a commercial bakery by incorporating fenugreek flour into a standard wheat bread formula. Whole wheat bread was prepared by the same formula in the same bakery using wheat flour. Eight diet-controlled diabetic subjects were served two slices (56g) and 5% fenugreek. Blood glucose and insulin were tested periodically over a 4-hour period after consumption. The tests were run on two occasions 1 week apart, once with the fenugreek bread and once with regular bread. The study was double-blind, and the order was randomized and balanced. Fenugreek and whole wheat bread samples were evaluated for sensory attributes and nutrient composition. There was no statistically significant difference in proximate composition, color, firmness, texture, and flavor intensity between the fenugreek and wheat bread (P>.05). The area under the curve for glucose and insulin was lower in the fenugreek condition, but only reached significance with insulin (P<.05). The fenugreek-containing bread was indistinguishable from the whole wheat bread control. Normally, fenugreek flour impacts bread quality negatively. The bread maintained fenugreek's functional property of reducing insulin resistance. Acceptable baked products can be prepared with added fenugreek, which will reduce insulin resistance and treat type 2 diabetes.