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.

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.

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.

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.

A Snack Formulated with Ingredients to Slow Carbohydrate Digestion and Absorption Reduces the Glycemic Response in Humans: A Randomized Controlled Trial

Candida J. Rebello,William D. Johnson,Yang Pan,Sandra Larrivee,Dachuan Zhang,Mark Nisbet,Jodee Johnson,YiFang Chu,Frank L. Greenway 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.1

This study compared the effect of a snack with ingredients to slow carbohydrate digestion (Test-snack) on postprandial blood glucose and insulin concentrations and subjective appetite ratings. We hypothesized that Test-snack would lower glucose and insulin responses and reduce appetite compared with a Control-snack. Overweight or obese subjects (n = 17) completed a randomized crossover study. Glucose, insulin, and appetite ratings were measured before consuming each snack or white bread (Bread) and over a period of 4 h. Subjects received Test-snack, Control-snack, or Bread in random order at least a week apart. The a priori primary outcome was the glucose response, and the secondary outcomes were appetite ratings and insulin responses. Mixed effects statistical models were used to perform analysis of variance in terms of the area under curve (AUC) and at specific time points. The 2-h AUC for glucose was significantly lower with Test-snack compared to Control-snack and Bread (AUC and 95% confidence intervals: Test = 2186.43 [1783.36–2589.51]; Control = 3293.75 [2893.97–3693.54]; Bread = 2800.28 [2405.79–3194.77] mg/dL · min). Four-hour AUC for glucose, and insulin, followed a similar pattern except that Test-snack did not differ from Bread. The glucose concentrations peaked at 45 min under all three conditions, but Test-snack elicited a lower response than Control-snack and Bread (P < .01). Test increased fullness and satisfaction and reduced hunger and prospective intake compared to Bread (P < .02), but was not significantly different from Control-snack. Ingredients that slow carbohydrate digestion in a snack reduce the postprandial glucose and insulin responses compared to a product without these ingredients.