Vitamin K Insufficiency in the Indian Population: Pilot Observational Epidemiology Study.

BACKGROUND: The fat-soluble K vitamins K1 and K2 play an essential role in the blood coagulation cascade and are made available predominantly through selective dietary intakes. They are less known for their nonessential roles in a family of vitamin K-dependent proteins that promote various functions of organs and systems in the body. A lack of vitamin K can characterize vitamin and nutritional element insufficiency, which is different from a clinically apparent vitamin deficiency. OBJECTIVE: This epidemiological study evaluated the nutritional status of vitamin K in a sample of the Indian population and vitamin K content in staple Indian foods. METHODS: Serum levels of vitamin K1 and vitamin K2 in the form of menaquinone-7 (MK-7) were assessed via high-performance liquid chromatography coupled with fluorescence detection in 209 patients with type 2 diabetes, 50 healthy volunteers, and common staple foods in India. RESULTS: After comparing populations with high and low serum vitamin K levels from various geographical regions, our results indicated that the sample of healthy Indian individuals and the sample of Indian patients with type 2 diabetes had low (insufficient) levels of vitamin K2 (MK-7; range 0.3-0.4 ng/mL). No significant differences existed in vitamin K1-related and MK-7-related values between healthy male and female subjects, between male and female subjects with diabetes, and between the healthy sample and the sample of patients with diabetes. The staple, commonly consumed Indian foods that were tested in this study had undetectable levels of vitamin K2, while levels of vitamin K1 varied widely (range 0-37 µg/100 g). CONCLUSIONS: Based on our sample's low serum levels of vitamin K2 (MK-7) as well as the low levels of vitamin K2 in their typical diet, we propose that the general Indian population could benefit from the consumption of vitamin K2 in the form of MK-7 supplements. TRIAL REGISTRATION: Clinical Trials Registry - India CTRI/2019/05/014246; http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=21660&EncHid=&userName=014246; Clinical Trials Registry - India CTRI/2019/03/018278; http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=32349&EncHid=&userName=018278.

p-Synephrine, ephedrine, p-octopamine and m-synephrine: Comparative mechanistic, physiological and pharmacological properties.

Confusion and misunderstanding exist regarding the lack of cardiovascular and other adverse health effects of p-synephrine and p-octopamine relative to ephedrine and m-synephrine (phenylephrine) which are known for their effects on the cardiovascular system. These four molecules have some structural similarities. However, the structural and stereochemical differences of p-synephrine and p-octopamine as related to ephedrine and m-synephrine result in markedly different adrenergic receptor binding characteristics as well as other mechanistic differences which are reviewed. p-Synephrine and p-octopamine exhibit little binding to α-1, α-2, ß-1 and ß-2 adrenergic receptors, nor are they known to exhibit indirect actions leading to an increase in available levels of endogenous norepinephrine and epinephrine at commonly used doses. The relative absence of these mechanistic actions provides an explanation for their lack of production of cardiovascular effects at commonly used oral doses as compared to ephedrine and m-synephrine. As a consequence, the effects of ephedrine and m-synephrine cannot be directly extrapolated to p-synephrine and p-octopamine which exhibit significantly different pharmacokinetic, and physiological/pharmacological properties. These conclusions are supported by human, animal and in vitro studies that are discussed.

Review of Published Bitter Orange Extract and p-Synephrine Adverse Event Clinical Study Case Reports.

p-Synephrine is the primary active ingredient in bitter orange (Citrus aurantium) extract and is present in other citrus species. This review summarizes all known case reports that have been published regarding adverse events associated with multi-ingredient dietary supplements containing bitter orange extract. A common characteristic of all the case studies was the assumption that if bitter orange extract is listed on the label of the product it is the most likely cause of any adverse effect, although in no case was the presence of p-synephrine determined or a direct link demonstrated. No case study reviewed the existing published literature, and all failed to note that numerous clinical studies have not demonstrated adverse effects at commonly used doses. Most studies did not indicate the composition of the product involved, and no study analyzed the product in question. In no case was a direct correlation between the event and p-synephrine made. Although p-synephrine and ephedrine have some structural similarity, the structural differences result in markedly different pharmacokinetic, physiological, and pharmacological effects, and thus the effects produced by ephedrine cannot be extrapolated to p-synephrine.

The fallacy of enzymatic hydrolysis for the determination of bioactive curcumin in plasma samples as an indication of bioavailability: a comparative study.

BACKGROUND: Numerous health benefits have been demonstrated for curcumin which is extracted from turmeric (Curcuma longa L). However, due to its poor absorption in the free form in the gastrointestinal tract and rapid biotransformation, various formulations have been developed to enhance its bioavailability. Previous studies indicate that the free form of curcumin is more bioactive than its conjugated counterparts in target tissues. Most curcumin pharmacokinetics studies in humans designed to assess its absorption and bioavailability have measured and reported total (free plus conjugated) curcumin, but not free, bioactive curcumin in the plasma because enzymatic hydrolysis was employed prior to its extraction and analysis. Therefore, the bioavailability of free curcumin cannot be determined. METHODS: Eight human subjects (4 male, 4 female) consumed a single dose of 400 mg curcumin in an enhanced absorption formulation, and blood samples were collected over 6 h. Plasma was treated either with or without glucuronidase/sulfatase prior to extraction. Curcumin and its major metabolites were analyzed using HPLC-tandem mass spectrometry. In addition, the literature was searched for pharmacokinetic studies involving curcumin using PubMed and Google Scholar, and the reported bioavailability data were compared based on whether hydrolysis of plasma samples was used prior to sample analysis. RESULTS: Hydrolysis of blood plasma samples prior to extraction and reporting the results as "curcumin" obscures the amount of free, bioactive curcumin and total curcuminoids as compared to non-hydrolyzed samples. As a consequence, the data and biological effects reported by most pharmacokinetic studies are not a clear indication of enhanced plasma levels of free bioactive curcumin due to product formulations, leading to a misrepresentation of the results of the studies and the products when enzymatic hydrolysis is employed. CONCLUSIONS: When enzymatic hydrolysis is employed as is the case with most studies involving curcumin products, the amount of free bioactive curcumin is unknown and cannot be determined. Therefore, extreme caution is warranted in interpreting published analytical results from biological samples involving ingestion of curcumin-containing products. TRIAL REGISTRATION: ClinicalTrails.gov, trial identifying number NCT04103788 , September 24, 2019. Retrospectively registered.

Role of Vitamin D and Its Receptors in the Pathophysiology of Chronic Rhinosinusitis.

OBJECTIVES: Chronic rhinosinusitis (CRS) is a disease that represents a challenging therapeutic problem. Vitamin D and its receptors (VDR) are involved in the regulation of the immune system and may play role in CRS. Objectives of this study were to assess the relationships between the total concentration of vitamin D (25VD3) in sera, vitamin D receptor (VDR) expression, 1α-hydroxylase expression, and clinical data, including age, gender, Sino-Nasal Outcome Test (SNOT-22), computerized tomography (CT) scan, allergy status, and vitamin D supplementation in CRS patients with (CRSwNP) and without nasal polyps (CRSsNP), and in a control group. METHODS: The studied group comprised 52 patients with CRS without nasal polyps (sNP), 55 with CRS with nasal polyps (wNP), and 59 in the control group. The endpoints were determined by appropriate methods. We conducted immunohistochemical staining of gathered tissue from the ostiomeatal complex for determination of VDR and 1α-hydroxylase. Analytical results were compared with clinical data as already noted. RESULTS: A decrease in VDR nuclear staining occurred in CRS patients as compared to controls. Insignificant differences were observed in 1α-hydroxylase, expression in all studied groups, while VDR and cytochrome CYP27B1 protein expression (1α-hydroxylase) correlated with clinical data. CONCLUSIONS: The data provide evidence that indicates that vitamin D and its receptor and enzymes may play a role in CRS.

Acute hematological and mood perception effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine: A placebo-controlled, double-blind study.

The purpose of this study was to examine acute hematological and mood perception responses to supplementation with p-synephrine alone and in combination with caffeine during quiet sitting. Sixteen subjects visited the laboratory on 6 occasions and were given (in randomized double-blind manner) 103-mg p-synephrine (S), 233-mg caffeine + 104-mg p-synephrine, 240-mg caffeine, 337-mg caffeine + 46-mg p-synephrine, 325-mg caffeine, or a placebo (PL). The subjects sat quietly for 3 hr while completing mood state questionnaires every 30 min. Venous blood samples were collected at baseline (pre) and 3 hr (post) to determine immune, lipid, and chemistry panels. Compared with PL, no significant supplement differences were observed during the S trial with the exception of differential time effects seen in hematocrit (decrease in PL, no change in S), triglycerides and very low-density lipoproteins (no changes in PL, significant decreases in S), and iron (no change in PL, significant elevation in S). Supplements containing caffeine showed increased feelings of attention, excitement, energy, and vigor. These data indicate that consumption of 103-mg p-synephrine does not negatively impact acute blood parameters, does not augment the effects of caffeine, or produce stimulant-like perceptual mood effects.

Effect of a Fibroin Enzymatic Hydrolysate on Memory Improvement: A Placebo-Controlled, Double-Blind Study.

The consumption of a specifically prepared silk fibroin protein enzymatic hydrolysate (FPEH) has been reported to improve cognitive function in healthy humans. The objective of the current study is to evaluate the dose-dependent effects of the FPEH on memory. Healthy adults with an average age of approximately 55 years were administered doses of 0, 280, 400 and 600 mg of FPEH per day in two divided doses for 3 weeks. The Rey-Kim Auditory Verbal Learning Test and the Rey-Kim Complex Figure Test of the Rey-Kim Memory Test were used to evaluate memory at baseline and after 3 weeks. The scores for each test were combined into the memory quotient score (MQ). Learning gradient, memory maintenance, retrieval efficacy, and drawing/recall scores were also compared. After 3 weeks of FPEH, dose-dependent increases were observed for the MQ, the learning gradient, the numbers of words remembered, the retrieval efficiency, and drawing/recall. The optimal dose for FPEH was 400 or 600 mg, depending on the end point measured. No adverse effects were reported. FPEH significantly improved measurements of memory in healthy adults by 3 weeks at doses over 280 mg daily, with an apparent plateau effect at 400-600 mg daily.

Safety evaluation of p-synephrine following 15 days of oral administration to healthy subjects: A clinical study.

Extracts of bitter orange (BOE, Citrus aurantium L.) and its primary protoalkaloid p-synephrine are extensively consumed as dietary supplements. p-Synephrine is also present in foods and juices prepared from various Citrus species. The safety of p-synephrine has been questioned as a result of structural similarities with ephedrine. This study assessed the cardiovascular (stimulant) and hemodynamic effects of BOE (49 mg p-synephrine) daily given to 16 healthy subjects for 15 days in a placebo-controlled, cross-over, double-blinded study. A physical evaluation by a cardiologist, as well as heart rates, blood pressures, and electrocardiograms were determined, and blood samples were drawn at baseline, and Days 5, 10, and 15. Serum levels for caffeine and p-synephrine were measured at 1 and 2 weeks. Subjects completed a 10-item health and metabolic questionnaire at baseline and on Day 15. No significant changes occurred in heart rate, electrocardiograms, systolic blood or diastolic pressures, blood cell counts, or blood chemistries in either the control or p-synephrine treated groups at any time point. No adverse effects were reported in response to the bitter orange (p-synephrine). Caffeine consumed by the participants varied markedly. Under these experimental conditions, BOE and p-synephrine were without stimulant (cardiovascular) and adverse effects.

Acute cardiovascular effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine in human subjects: A placebo-controlled, double-blind study.

The purpose was to examine cardiovascular responses to supplementation with p-synephrine alone and in combination with caffeine during quiet sitting. Sixteen subjects were given (in double-blind manner) either 103 mg of p-synephrine (S), 233 mg of caffeine +104 mg of p-synephrine (LC + S), 240 mg of caffeine (LC), 337 mg of caffeine +46 mg of p-synephrine (HC + S), 325 mg of caffeine (HC), or a placebo. The subjects sat quietly for 3 hr while heart rate (HR) and blood pressure were measured. Only HC + S and HC significantly increased mean systolic blood pressure (SBP) during the second hour and tended to increase mean SBP during the third hour. Mean diastolic blood pressure in S was significantly lower than the other trials during the first and second hours, and mean arterial pressure was significantly lower in S compared to the LC, LC + S, HC, and HC + S trials. No differences were observed in HR. Consumption of p-synephrine may acutely reduce diastolic blood pressure and mean arterial pressure and not affect SBP or HR during quiet sitting. The addition of p-synephrine to caffeine did not augment SBP or HR indicating that consumption of up to 104 mg of p-synephrine does not induce cardiovascular stress during quiet sitting.

Comparative Oral Absorption of Curcumin in a Natural Turmeric Matrix with Two Other Curcumin Formulations: An Open-label Parallel-arm Study.

Curcuminoids are the major bioactive molecules in turmeric, and poor bioavailability deters them from being the major components of many health and wellness applications. This study was conducted to assess the bioavailability of a completely natural turmeric matrix formulation (CNTMF) and compare its bioavailability with two other commercially available formulations, namely, curcumin with volatile oil (volatile oil formulation) and curcumin with phospholipids and cellulose (phospholipid formulation) in healthy human adult male subjects (15 each group) under fasting conditions. Each formulation was administrated orally as a single 500-mg dose in capsule form, and blood samples were analyzed by liquid chromatography mass spectrometry at various time intervals up to 24 h. The ingestion of the CNTMF was very well absorbed and resulted in a mean curcuminoids plasma Cmax of 170.14 ng/mL (Tmax  = 4 h) compared with 47.54 ng/mL and 69.63 ng/mL for the volatile oil (Tmax  = 3 h) and phospholipid (Tmax  = 2.25 h) formulations, respectively. The extent of absorption of total curcuminoids in the blood for the CNTMF was 6× greater than volatile oil formulation and 5× greater than phospholipids formulation. The results of this study indicate that curcumin in a natural turmeric matrix exhibited greater bioavailability than the two comparator products. Copyright © 2017 John Wiley & Sons, Ltd.

A Novel Highly Bioavailable Curcumin Formulation Improves Symptoms and Diagnostic Indicators in Rheumatoid Arthritis Patients: A Randomized, Double-Blind, Placebo-Controlled, Two-Dose, Three-Arm, and Parallel-Group Study.

Rheumatoid arthritis (RA) is an autoimmune, chronic systemic inflammatory disorder. The long-term use of currently available drugs for the treatment of RA has many potential side effects. Natural phytonutrients may serve as alternative strategies for the safe and effective treatment of RA, and curcuminoids have been used in Ayurvedic medicine for the treatment of inflammatory conditions for centuries. In this study, a novel, highly bioavailable form of curcumin in a completely natural turmeric matrix was evaluated for its ability to improve the clinical symptoms of RA. A randomized, double-blind, placebo-controlled, three-arm, parallel-group study was conducted to evaluate the comparative efficacy of two different doses of curcumin with that of a placebo in active RA patients. Twelve patients in each group received placebo, 250 or 500 mg of the curcumin product twice daily for 90 days. The responses of the patients were assessed using the American College of Rheumatology (ACR) response, visual analog scale (VAS), C-reactive protein (CRP), Disease Activity Score 28 (DAS28), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) values. RA patients who received the curcumin product at both low and high doses reported statistically significant changes in their clinical symptoms at the end of the study. These observations were confirmed by significant changes in ESR, CPR, and RF values in patients receiving the study product compared to baseline and placebo. The results indicate that this novel curcumin in a turmeric matrix acts as an analgesic and anti-inflammatory agent for the management of RA at a dose as low as 250 mg twice daily as evidenced by significant improvement in the ESR, CRP, VAS, RF, DAS28, and ACR responses compared to placebo. Both doses of the study product were well tolerated and without side effects.

Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p-Synephrine.

Citrus aurantium L. (bitter orange) extracts that contain p-synephrine as the primary protoalkaloid are widely used for weight loss/weight management, sports performance, appetite control, energy, and mental focus and cognition. Questions have been raised about the safety of p-synephrine because it has some structural similarity to ephedrine. This review focuses on current human, animal, in vitro, and mechanistic studies that address the safety, efficacy, and mechanisms of action of bitter orange extracts and p-synephrine. Numerous studies have been conducted with respect to p-synephrine and bitter orange extract because ephedra and ephedrine were banned from use in dietary supplements in 2004. Approximately 30 human studies indicate that p-synephrine and bitter orange extracts do not result in cardiovascular effects and do not act as stimulants at commonly used doses. Mechanistic studies suggest that p-synephrine exerts its effects through multiple actions, which are discussed. Because p-synephrine exhibits greater adrenergic receptor binding in rodents than humans, data from animals cannot be directly extrapolated to humans. This review, as well as several other assessments published in recent years, has concluded that bitter orange extract and p-synephrine are safe for use in dietary supplements and foods at the commonly used doses. Copyright © 2017 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.

Roles of Vitamins D and K, Nutrition, and Lifestyle in Low-Energy Bone Fractures in Children and Young Adults.

The research on skeletal system health in children and young adults, while recognizing the important role of calcium and vitamin D, goes beyond these nutritional standards. This review focuses on the role of vitamin K in combination with vitamin D and other factors in bone health. The current understanding is that maintaining bone health and prevention of low-energy fractures in any pediatric population includes nutritional factors combined with an active lifestyle. Calcium, vitamin D, and vitamin K supplementation contribute independently and collectively to bone health. The beneficial role of vitamin K, particularly vitamin K2 as menaquinone-7 (MK-7), in bone and cardiovascular health is reasonably well supported scientifically, with several preclinical, epidemiological, and clinical studies published over the last decade. Osteocalcin and matrix-Gla (glutamate-containing) protein (MGP) exemplify vitamin K-dependent proteins involved in building bone matrix and keeping calcium from accumulating in the arterial walls, respectively. An important part of the mechanism of vitamin K involves carboxylation and posttranslational activation of the family of vitamin K-dependent proteins, which prevent expression of pro-inflammatory factors and support improvement in bone mineral concentration, bone mineral density, and the quality of bone matrix. Understanding the combined approach to a healthy skeletal system in children and young adults, including the roles of vitamins D and K, calcium, healthy diet, and exercise, is particularly important in view of reports of subclinical insufficiency of vitamins D and K in otherwise healthy pediatric populations with low-energy bone fractures.

Hepatoprotective Effects of a Proprietary Glycyrrhizin Product during Alcohol Consumption: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

Traditionally, licorice has been used to treat liver problems. Glycyrrhizin, the primary active compound, has been shown to suppress elevations in liver enzymes that occur when the liver becomes diseased or damaged. This randomized, double-blind, placebo-controlled, crossover study evaluated the hepatoprotective effects of a proprietary glycyrrhizin product during alcohol consumption. Twelve healthy individuals (six male and six female subjects) in a clinic setting consumed vodka nightly for 12 days with the glycyrrhizin product or placebo (blank control), achieving a blood alcohol level of 0.12%. Liver function enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase and serum reduced glutathione were measured at overnight visits 1, 6, and 12. In the alcohol only group, AST, ALT, and GGT significantly increased from baseline (overnight visit 1) to overnight visit 12. In the active group, no statistically significant increases were observed for AST, ALT, and GGT, while alkaline phosphatase significantly decreased and plasma glutathione decreased relative to the alcohol control group. These results suggest that consumption of the proprietary glycyrrhizin study product during alcohol consumption may support improved liver health compared with drinking alcohol alone. Copyright © 2016 John Wiley & Sons, Ltd.

The Effects of Supplementation with p-Synephrine Alone and in Combination with Caffeine on Metabolic, Lipolytic, and Cardiovascular Responses during Resistance Exercise.

OBJECTIVE: The purpose of this study was to examine the metabolic, lipolytic, and cardiovascular responses to supplementation with p-synephrine alone and in combination with caffeine during resistance exercise (RE). METHODS: Twelve healthy men performed a control RE protocol (6 × 10 repetitions of squats) and were randomly assigned (using a double-blind crossover design with random protocol sequencing) to a supplement sequence: p-synephrine (S; 100 mg), p-synephrine + caffeine (SCF; 100 mg of p-synephrine plus 100 mg of caffeine), or a placebo (P). Subjects reported to the lab at a standard time, consumed a supplement, sat quietly for 45 minutes, performed the RE protocol, and sat quietly for 30 minutes. Blood samples were collected at rest (T1), after sitting quietly for 45 minutes (T2), immediately following RE (T3), and 15 minutes (T4) and 30 minutes (T5) postexercise. Oxygen consumption (VO2) and heart rate (HR) data were collected throughout. RESULTS: Serum glycerol was significantly elevated at T2 only in S and SCF and T3 to T5 in all treatments. Nonesterified fatty acid (NEFA) concentrations did not differ between treatments. Plasma glucose was significantly elevated compared to T1 with highest area under the curve values seen in SCF. Mean VO2 and energy expenditure (EE) were significantly higher in S and SCF through 30 minutes postexercise. Fat oxidation rates favored S and SCF between 25 and 30 minutes postexercise. Mean HR during RE was significantly highest in SCF. CONCLUSIONS: Supplementation with S and SCF increases lipolysis primarily at rest and increases VO2, EE, and fat oxidation rates 30 minutes following RE. No HR changes were observed unless caffeine was added.

Inhibition of TNF-α, IL-1α, and IL-1ß by Pretreatment of Human Monocyte-Derived Macrophages with Menaquinone-7 and Cell Activation with TLR Agonists In Vitro.

Circulatory markers of low-grade inflammation such as tumor necrosis factor-alpha (TNF-α), interleukin-1 alpha (IL-1α), and interleukin-1 beta (IL-1ß) positively correlate with endothelial damage, atheroma formation, cardiovascular disease, and aging. The natural vitamin K2-menaquinone-7 (MK-7) added to the cell culture of human monocyte-derived macrophages (hMDMs) at the same time as toll-like receptor (TLR) agonists did not influence the production of TNF-α. When the cells were pretreated up to 6 h with MK-7 before treatment with TLR agonists, MK-7 did not inhibit significantly the production of TNF-α after the TLR activation. However, 30 h pretreatment of hMDMs with at least 10 µM of MK-7 effectively and dose dependently inhibited the proinflammatory function of hMDMs. Pretreatment of hMDMs with 10 µM of MK-7 for 30 h resulted in 20% inhibition of TNF-α production after lipopolysaccharide (LPS) activation (P < .05) and 43% inhibition after macrophage-activating lipopeptide (MALP) activation (P < .001). Pathogen-associated molecular pattern (PMPP) activation was inhibited by 20% with MK-7 pretreatment; however, this inhibition was not statistically significant. The 30 h pretreatment of a THP-1-differentiated monocyte cell line with MK-7 resulted in a dose-dependent downregulation of TNFα, IL-1α, and IL-1ß gene expression as evaluated by RNA semiquantitative reverse transcription polymerase chain reaction (RT-PCR). MK-7 is able to modulate immune and inflammatory reactions in the dose-response inhibition of TNF-α, IL-1α, and IL-1ß gene expression and protein production by the healthy hMDMs in vitro.

Cardiovascular Safety of Oral p-Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo-Controlled Cross-over Clinical Trial.

Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p-synephrine are widely consumed in combination with multiple herbal ingredients for weight management and sports performance. p-Synephrine is also present in juices and foods derived from a variety of Citrus species. Questions exist regarding the safety of p-synephrine because of structural similarities with other biogenic amines. This study assessed the cardiovascular (stimulatory) effects of bitter orange extract (49-mg p-synephrine) given to 18 healthy subjects (nine men and nine women) in a double-blinded, placebo-controlled cross-over study. Heart rates, blood pressures, and electrocardiograms were determined at baseline, 30, 60, 90 min, 2, 4 , 6, and 8 h. Blood samples were drawn at baseline, 2 h and 8 h for serum chemistries, blood cell counts, and p-synephrine and caffeine levels. No significant changes occurred in electrocardiograms, heart rates, systolic blood pressure, blood chemistries, or blood cell counts at any time point in either control or p-synephrine treated group. A small (4.5 mmHg) decrease in diastolic blood pressure occurred in the p-synephrine treated group at 60 min. No adverse effects were reported. Caffeine ingestion varied markedly among the participants. p-Synephrine does not act as a stimulant at the dose used. Copyright © 2016 John Wiley & Sons, Ltd.

A Review of Natural Stimulant and Non-stimulant Thermogenic Agents.

Obesity and overweight are major health issues. Exercise and calorie intake control are recognized as the primary mechanisms for addressing excess body weight. Naturally occurring thermogenic plant constituents offer adjunct means for assisting in weight management. The controlling mechanisms for thermogenesis offer many intervention points. Thermogenic agents can act through stimulation of the central nervous system with associated adverse cardiovascular effects and through metabolic mechanisms that are non-stimulatory or a combination thereof. Examples of stimulatory thermogenic agents that will be discussed include ephedrine and caffeine. Examples of non-stimulatory thermogenic agents include p-synephrine (bitter orange extract), capsaicin, forskolin (Coleus root extract), and chlorogenic acid (green coffee bean extract). Green tea is an example of a thermogenic with the potential to produce mild but clinically insignificant undesirable stimulatory effects. The use of the aforementioned thermogenic agents in combination with other extracts such as those derived from Salacia reticulata, Sesamum indicum, Lagerstroemia speciosa, Cissus quadrangularis, and Moringa olifera, as well as the use of the carotenoids as lutein and fucoxanthin, and flavonoids as naringin and hesperidin can further facilitate energy metabolism and weight management as well as sports performance without adverse side effects. © 2016 The Authors Phytotherapy Research published by John Wiley & Sons Ltd.

Safety and Efficacy of Banaba-Moringa oleifera-Green Coffee Bean Extracts and Vitamin D3 in a Sustained Release Weight Management Supplement.

This 60-day, 30-subject pilot study examined a novel combination of ingredients in a unique sustained release (Carbopol matrix) tablet consumed twice daily. The product was composed of extracts of banaba leaf, green coffee bean, and Moringa oleifera leaf and vitamin D3. Safety was assessed using a 45-measurement blood chemistry panel, an 86-item self-reported Quality of Life Inventory, bone mineral density, and cardiovascular changes. Efficacy was assessed by calculating a body composition improvement index (BCI) based on changes in dual energy X-ray absorptiometry measured fat mass (FM) and fat-free mass (FFM) as well as between the study group (SG) and a historical placebo group. No changes occurred in any blood chemistry measurements. Positive changes were found in the Quality of Life (QOL) inventory composite scores. No adverse effects were observed. Decreases occurred in FM (p = 0.004) and increases in FFM (p = 0.009). Relative to the historical placebo group, the SG lost more FM (p < 0.0001), gained more FFM (p = <0.0001), and had a negative BCI of -2.7 lb. compared with a positive BCI in the SG of 3.4 lb., a 6.1 discordance (p = 0.0009). The data support the safety and efficacy of this unique product and demonstrate importance of using changes in body composition versus scale weight and BMI.