CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

Ashwagandha

Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants

Abstract

Background: Withania somnifera is an herbal medicine that has been known to possess memory-enhancing properties. The current study involved an assessment of cognitive and psychomotor effects of Withania somnifera extract in healthy human participants.

Materials and methods: In this prospective, double-blind, multi-dose, placebo-controlled, crossover study, 20 healthy male participants were randomized to receive 250 mg two capsules twice daily of an encapsulated dried aqueous extract of roots and leaves of Withania somnifera or a matching placebo for a period of 14 days. Cognitive and psychomotor performance was assessed pre-dose (day 1) and at 3 hrs post-dose on day 15 using a battery of computerized psychometric tests. After a washout period of 14 days, the subjects crossed-over to receive the other treatment for a further period of 14 days as per prior randomization schedule. Same battery of test procedures were performed to assess cognitive and psychomotor performance.

Results: Significant improvements were observed in reaction times with simple reaction, choice discrimination, digit symbol substitution, digit vigilance, and card sorting tests with Withania somnifera extract compared to placebo. However, no effect can be seen with the finger tapping test.

Conclusion: These results suggest that Withania somnifera extract can improve cognitive and psychomotor performance and may, therefore, be a valuable adjunct in the treatment of diseases associated with cognitive impairment.

Source: Pingali U, Pilli R, Fatima N. “Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants.” Pharmacognosy Research (2014) ;6(1):12–8.

A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults

Abstract

Context: Stress is a state of mental or emotional strain or tension, which can lead to underperformance and adverse clinical conditions. Adaptogens are herbs that help in combating stress. Ayurvedic classical texts, animal studies and clinical studies describe Ashwagandha as a safe and effective adaptogen.

Aims: The aim of the study was to evaluate the safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha roots in reducing stress and anxiety and in improving the general well-being of adults who were under stress.

Settings and design: Single center, prospective, double-blind, randomized, placebo-controlled trial.

Materials and methods: A total of 64 subjects with a history of chronic stress were enrolled into the study after performing relevant clinical examinations and laboratory tests. These included a measurement of serum cortisol, and assessing their scores on standard stress-assessment questionnaires. They were randomized to either the placebo control group or the study drug treatment group, and were asked to take one capsule twice a day for a period of 60 days. In the study drug treatment group, each capsule contained 300 mg of high-concentration full-spectrum extract from the root of the Ashwagandha plant. During the treatment period (on Day 15, Day 30 and Day 45), a follow-up telephone call was made to all subjects to check for treatment compliance and to note any adverse reactions. Final safety and efficacy assessments were done on Day 60.

Statistical analysis: t-test, Mann-Whitney test.

Results: The treatment group that was given the high-concentration full-spectrum Ashwagandha root extract exhibited a significant reduction (P<0.0001) in scores on all the stress-assessment scales on Day 60, relative to the placebo group. The serum cortisol levels were substantially reduced (P=0.0006) in the Ashwagandha group, relative to the placebo group. The adverse effects were mild in nature and were comparable in both the groups. No serious adverse events were reported.

Conclusion: The findings of this study suggest that a high-concentration full-spectrum Ashwagandha root extract safely and effectively improves an individual's resistance towards stress and thereby improves self-assessed quality of life.

Source: Chandrasekhar K, Kapoor J, Anishetty S. “A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults.” Indian J Psychol Med. (2012);34(3):255–62.;

Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera) in healthy volunteers

Abstract

Ashwagandha (Withania somnifera) (WS), a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age: 18-30 years, and BMI: 19-30) were enrolled. After baseline investigations, they received WS capsules (Rx) (aqueous extract, 8:1) daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day × 10 days, 1 000 mg/day × 10 days, 1 250 mg/day × 10 days). Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat % were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar's test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

Source: Raut AA, Rege NN, Tadvi FM, Solanki PV, Kene KR, Shirolkar SG, Pandey SN, Vaidya RA, Vaidya AB. “Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera) in healthy volunteers.” J Ayurveda Integr Med. (2012);3(3):111–4.

Withania somnifera Root Extract Enhances Telomerase Activity in the Human HeLa Cell Line

Abstract

Aging is a decelerating unidirectional process of life. Shortening of telomeric DNA, the (TTAGGG)n hexanucleotide repeats, which form the caps at the chromosome ends, is implicated to determine the aging process, and more importantly the healthy lifespan itself. Telomerase, a ribonucleoprotein having reverse transcriptase activity, arrests telomere loss through addition of the TTAGGG repeats de novo, to the ends of the chromosome. The telomere/telomerase maintenance is an inevitable necessity to delay aging and for a healthy lifespan. Here, we report the potential of full-spectrum, high concentration Ashwagandha (Withania somnifera), an Ayurvedic medicinal herb, root extract to increase telomerase activity. HeLa cells, when treated with various concentrations of Ashwagandha root extract, showed an increase in telomerase activity measured with the established Telomerase Rapid Amplification Protocol (TRAP) assay. Ashwagandha root extract increased telomerase activity with highest enhancement of ~45% at 10 - 50 μg concentration. Thus, Ashwagandha root extract has the anti-aging inducing potential.

Source: Raguraman, V. and Subramaniam, J. “Withania somnifera Root Extract Enhances Telomerase Activity in the Human HeLa Cell Line.” Advances in Bioscience and Biotechnology (2016), 7, 199–204.

A randomized, double blind placebo controlled study of efficacy and tolerability of Withaina somnifera extracts in knee joint pain

Abstract

Background: Root extracts of Withania somnifera (Ashwagandha) are known to possess analgesic, anti-inflammatory and chondroprotective effects. An aqueous extract of roots plus leaves of this plant has shown to yield higher percentages of withanolide glycosides and, accordingly, may possess better analgesic, anti-inflammatory and chondroprotective effects than root alone extracts.

Objectives: To evaluate efficacy and tolerability of a standardized aqueous extract of roots plus leaves of W. somnifera in patients with knee joint pain and discomfort.

Material and methods: Sixty patients with knee joint pain and discomfort were randomized in a double-blind manner to W. somnifera 250 mg, W. somnifera 125 mg and placebo, all given twice daily. Assessment was done by Modified WOMAC, Knee Swelling Index (KSI), Visual Analogue Scale (VAS) at baseline and at the end of 4, 8, 12 weeks. Tolerability was assessed by incidence of adverse effects in treatment groups. Student's ‘t’ test and ANOVA were used to compare mean change from baseline within and between the study groups. A p < 0.05 was considered significant.

Results: At the end of 12 weeks, compared to baseline and placebo, significant reductions were observed in mean mWOMAC and KSI in W. somnifera 250 mg (p < 0.001), W. somnifera 125 mg (p < 0.05) groups. VAS scores for pain, stiffness and disability were significantly reduced in W. somnifera 250 mg (p < 0.001), W. somnifera 125 mg (p < 0.01) groups. W. somnifera 250 mg group showed earliest efficacy (at 4 weeks). All treatments were well tolerated.

Conclusions: Both the doses of an aqueous extract of W. somnifera produced significant reduction in outcome variables, with the 250 mg group showing significantly better response. In addition, the therapeutic response appears to be dose-dependent and free of any significant GI disturbances.

Source: Ramakanth, G. S., Uday Kumar, C., Kishan, P. V., & Usharani, P. “A randomized, double blind placebo controlled study of efficacy and tolerability of Withaina somnifera extracts in knee joint pain.” Journal of Ayurveda and integrative medicine (2016), 7(3), 151–157.

Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root

Abstract

Hypoglycemic, diuretic and hypocholesterolemic effects of roots of W. somnifera (ashvagandha) were assessed on human subjects. Six mild NIDDM subjects and six mild hypercholesterolemic subjects were treated with the powder of roots of W. somnifera for 30 days. Suitable parameters were studied in the blood and urine samples of the subjects along with dietary pattern before and at the end of treatment period. Decrease in blood glucose was comparable to that of an oral hypoglycemic drug. Significant increase in urine sodium, urine volume, significant decrease in serum cholesterol, triglycerides, LDL (low density lipoproteins) and VLDL (very low density lipoproteins) cholesterol were observed indicating that root of W. somnifera is a potential source of hypoglycemic, diuretic and hypocholesterolemic agents. Clinical observations revealed no adverse effects.

Source: Andallu B, Radhika B. “Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root.” Indian J Exp Biol. (2000) ;38(6):607–9.

Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile male

Abstract

Objective: To investigate the impact of Withania somnifera roots on semen profile, oxidative biomarkers, and reproductive hormone levels of infertile men.

Patient(s): Seventy-five normal healthy fertile men (control subjects) and 75 men undergoing infertility screening.

Intervention(s): High-performance liquid chromatography assay procedure for quantization of vitamin A and E in seminal plasma. Biochemical parameters in seminal plasma were estimated by standard spectrophotometric procedures. Estimation of T, LH, FSH, and PRL in blood serum by RIA methods.

Main outcome measures(s): Before and after the treatment, seminal plasma biochemical parameters, antioxidant vitamins, and serum T, LH, FSH, and PRL levels were measured.

Result(s): Withania somnifera inhibited lipid peroxidation and protein carbonyl content and improved sperm count and motility. Treatment of infertile men recovered the seminal plasma levels of antioxidant enzymes and vitamins A, C, and E and corrected fructose. Moreover, treatment also significantly increased serum T and LH and reduced the levels of FSH and PRL.

Conclusion(s): The treatment with W. somnifera effectively reduced oxidative stress, as assessed by decreased levels of various oxidants and improved level of diverse antioxidants. Moreover, the levels of T, LH, FSH and PRL, good indicators of semen quality, were also reversed in infertile subjects after treatment with the herbal preparation.

Source: Ahmad MK, Mahdi AA, Shukla KK, Islam N, Rajender S, Madhukar D, Shankhwar SN, Ahmad S. “Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males.” Fertil Steril. (2010);94(3):989–96.

Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract

A Double-Blind, Randomized, Placebo-Controlled Trial
Abstract

Chronic stress has been associated with a number of illnesses, including obesity. Ashwagandha is a well-known adaptogen and known for reducing stress and anxiety in humans. The objective of this study was to evaluate the safety and efficacy of a standardized root extract of Ashwagandha through a double-blind, randomized, placebo-controlled trial. A total of 52 subjects under chronic stress received either Ashwagandha (300 mg) or placebo twice daily. Primary efficacy measures were Perceived Stress Scale and Food Cravings Questionnaire. Secondary efficacy measures were Oxford Happiness Questionnaire, Three-Factor Eating Questionnaire, serum cortisol, body weight, and body mass index. Each subject was assessed at the start and at 4 and 8 weeks. The treatment with Ashwagandha resulted in significant improvements in primary and secondary measures. Also, the extract was found to be safe and tolerable. The outcome of this study suggests that Ashwagandha root extract can be used for body weight management in adults under chronic stress.

Source: Choudhary, D., Bhattacharyya, S., & Joshi, K. “Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial.” Journal of evidence-based complementary & alternative medicine (2017), 22(1), 96–106.

Hypocholesteremic and antioxidant effects of Withania somnifera (Dunal) in hypercholesteremic rats

Abstract

Hypocholesteremic and antioxidant effects of Withania somnifera (WS) Dunal (Solanaceae) were investigated in hypercholesteremic male albino rats. When the root powder of WS was added to the diet at 0.75 and 1.5 gm/rat/day, hypercholesteremic animals registered significant decreases in total lipids (-40.54%; -50.69%), cholesterol (-41.58%; -53.01%) and triglycerides (-31.25%; - 44.85%) in plasma. On the other hand, significant increases in plasma HDL-cholesterol levels (+15.10%; +17.71%), HMG-CoA reductase activity (+19.51%; +26.02%) and bile acid content (+24.64%; +30.52%) of liver were noted in these animals. A similar trend was also noted in bile acid (+22.43%;+28.52%), cholesterol (+14.21%; +17.68%) and neutral sterol (+12.40%; +18.85%) excretion in the hypercholesteremic animals with WS administration. Further, a significant decrease in lipid-peroxidation (-35.29%; -36.52%) occurred in WS administered hypercholesteremic animals when compared to their normal counterparts. However, it appeared that WS root powder is also effective in normal subjects for decreasing lipid profiles.

Source: Visavadiya NP, Narasimhacharya AV. “Hypocholesteremic and antioxidant effects of Withania somnifera (Dunal) in hypercholesteremic rats.” Phytomedicine. (2007);14(2-3):136–42.

Resveratrol

Resveratrol improves health and survival of mice on a high-calorie diet

Abstract

Resveratrol (3,5,4′-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor- γ coactivator 1α (PGC-1α) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.

Source: Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., Pistell, P. J., Poosala, S., Becker, K. G., Boss, O., Gwinn, D., Wang, M., Ramaswamy, S., Fishbein, K. W., Spencer, R. G., Lakatta, E. G., … Sinclair, D. A. “Resveratrol improves health and survival of mice on a high-calorie diet.” Nature (2006), 444(7117), 337–342.

Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans

Summary: Resveratrol is a natural compound that affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here, we treated 11 healthy, obese men with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind crossover study for 30 days. Resveratrol significantly reduced sleeping and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1α protein levels, increased citrate synthase activity without change in mitochondrial content, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine-aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased. In conclusion, we demonstrate that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction.

Source: Silvie Timmers, Ellen Konings, Lena Bilet, Riekelt H. Houtkooper, et al. “Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans.” Cell Metabolism (2011) Vol 14, Issue 5.

Resveratrol and the mitochondria: From triggering the intrinsic apoptotic pathway to inducing mitochondrial biogenesis, a mechanistic view

Abstract

Background: Mitochondria, the power plants of the cell, are known as a cross-road of different cellular signaling pathways. These cytoplasmic double-membraned organelles play a pivotal role in energy metabolism and regulate calcium flux in the cells. It is well known that mitochondrial dysfunction is associated with different diseases such as neurodegeneration and cancer. A growing body of literature has shown that polyphenolic compounds exert direct effects on mitochondrial ultra-structure and function. Resveratrol is known as one of the most common bioactive constituents of red wine, which improves mitochondrial functions under in vitro and in vivo conditions.

Scope of review: This paper aims to review the molecular pathways underlying the beneficial effects of resveratrol on mitochondrial structure and functions. In addition, we discuss the chemistry and main sources of resveratrol.

Major conclusions: Resveratrol represents the promising effects on mitochondria in different experimental models. However, there are several reports on the detrimental effects elicited by resveratrol on mitochondria.

General significance: An understanding of the chemistry and source of resveratrol, its bioavailability and the promising effects on mitochondria brings a new hope to therapy of mitochondrial dysfunction-related diseases.

Source: Marcos Roberto de Oliveira, Seyed Fazel Nabavi, Azadeh Manayi, Maria Daglia, Zohreh Hajheydari, Seyed Mohammad Nabavi “Resveratrol and the mitochondria: From triggering the intrinsic apoptotic pathway to inducing mitochondrial biogenesis, a mechanistic view.” Biochimica et Biophysica Acta (2016)Volume 1860, Issue 4.

Mitochondrial Protection by Resveratrol

Abstract

Mitochondrial dysfunction and oxidative stress are thought to play important roles in mammalian aging. Resveratrol is a plant-derived polyphenol that exerts diverse anti-aging activities, mimicking some of the molecular and functional effects of dietary restriction. This review focuses on the molecular mechanisms underlying the mitochondrial protective effects of resveratrol, which could be exploited for the prevention or amelioration of age-related diseases in the elderly.

Source: Ungvari, Z., Sonntag, W. E., de Cabo, R., Baur, J. A., & Csiszar, A. “Mitochondrial protection by resveratrol.” Exercise and sport sciences reviews (2011), 39(3), 128–132.

Resveratrol Promotes Mitochondrial Biogenesis and Protects against Seizure-Induced Neuronal Cell Damage in the Hippocampus Following Status Epilepticus by Activation of the PGC-1α Signaling Pathway

Abstract

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is known to regulate mitochondrial biogenesis. Resveratrol is present in a variety of plants, including the skin of grapes, blueberries, raspberries, mulberries, and peanuts. It has been shown to offer protective effects against a number of cardiovascular and neurodegenerative diseases, stroke, and epilepsy. This study examined the neuroprotective effect of resveratrol on mitochondrial biogenesis in the hippocampus following experimental status epilepticus. Kainic acid was microinjected into left hippocampal CA3 in Sprague Dawley rats to induce bilateral prolonged seizure activity. PGC-1α expression and related mitochondrial biogenesis were investigated. Amounts of nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (Tfam), cytochrome c oxidase 1 (COX1), and mitochondrial DNA (mtDNA) were measured to evaluate the extent of mitochondrial biogenesis. Increased PGC-1α and mitochondrial biogenesis machinery after prolonged seizure were found in CA3. Resveratrol increased expression of PGC-1α, NRF1, and Tfam, NRF1 binding activity, COX1 level, and mtDNA amount. In addition, resveratrol reduced activated caspase-3 activity and attenuated neuronal cell damage in the hippocampus following status epilepticus. These results suggest that resveratrol plays a pivotal role in the mitochondrial biogenesis machinery that may provide a protective mechanism counteracting seizure-induced neuronal damage by activation of the PGC-1α signaling pathway.

Source: Chuang YC, Chen SD, Hsu CY, Chen SF, Chen NC, Jou SB. “Resveratrol Promotes Mitochondrial Biogenesis and Protects against Seizure-Induced Neuronal Cell Damage in the Hippocampus Following Status Epilepticus by Activation of the PGC-1α Signaling Pathway.” Int J Mol Sci. (2019);20(4):998.

Resveratrol Analysis and Degradation Study in Blueberry Samples by HPLC with Fluorescence Detection

Abstract

Separation and quantification of trans-resveratrol in blueberry extracts were achieved using high performance liquid chromatography (HPLC). Trans-resveratrol in blueberry juice was found to be at a high level of 16.60 ± 0.19 µg/mL. This antioxidant polyphenolic compound was also quantified, in two brands of blueberry powder, to be 236.4 ± 7.5 µg/g or 269.9 ± 5.7 µg/g. Degradation of trans-resveratrol was observed in standard solutions and in blueberry samples (juice and powder extracts). It was found that degradation of trans-resveratrol was more severe when it was exposed to room light at room temperature. Therefore, it is advisable to store blueberry juice at 4°C in the dark, and consume it within 1–3 days in order to benefit from adequate intake of the antioxidant in the juice.

Source: Meera Shanmuganathan &Paul C. H. Li. “Resveratrol Analysis and Degradation Study in Blueberry Samples by HPLC with Fluorescence Detection.” Journal of Liquid Chrom. (2009), Volume 32, Issue 20.

Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2 Ingestion Induces a Less Inflammatory Cytokine Profile and a Potentially Beneficial Shift in Gut Microbiota in Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

Abstract

Objective: This study determined whether older adults who consumed a probiotic mixture would have a greater proportion of circulating CD4+ lymphocytes, altered cytokine production, and a shift in intestinal microbiota toward a healthier microbial community.

Methods: Participants (70 ± 1 years [mean ± SEM]; n = 32) consumed a probiotic (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM2) or a placebo twice daily for 3 weeks with a 5-week washout period between intervention periods. Blood and stools were collected before and after each intervention. The percentage of circulating CD4+ lymphocytes and ex vivo mitogen-stimulated cell cytokine production were measured. In stools, specific bacterial targets were quantified via quantitative polymerase chain reaction (qPCR) and community composition was determined via pyrosequencing.

Results: During the first period of the crossover the percentage of CD4+ cells decreased with the placebo (48% ± 3% to 31% ± 3%, p < 0.01) but did not change with the probiotic (44% ± 3% to 42% ± 3%) and log-transformed concentrations of interleukin-10 increased with the probiotic (1.7 ± 0.2 to 3.4 ± 0.2, p < 0.0001) but not the placebo (1.7 ± 0.2 to 2.1 ± 0.2). With the probiotic versus the placebo a higher percentage of participants had an increase in fecal bifidobacteria (48% versus 30%, p < 0.05) and lactic acid bacteria (55% versus 43%, p < 0.05) and a decrease in Escherichia coli (52% versus 27%, p < 0.05). Several bacterial groups matching Faeacalibactierium prausnitzii were more prevalent in stool samples with the probiotic versus placebo.

Conclusions: The probiotic maintained CD4+ lymphocytes and produced a less inflammatory cytokine profile possibly due to the changes in the microbial communities, which more closely resembled those reported in healthy younger populations.

Source: Samuel J. Spaiser , MS,Tyler Culpepper , PhD,Carmelo Nieves Jr. , MS,Maria Ukhanova , PhD,Volker Mai , PhD,Susan S. Percival. “Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2 Ingestion Induces a Less Inflammatory Cytokine Profile and a Potentially Beneficial Shift in Gut Microbiota in Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.” Journal of the American College of Nutrition (2015), Volume 34, Issue 6.

Gynostemma

Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): A randomized, double‐blind, placebo‐controlled trial

Abstract

Objective: The effects of actiponin was investigated, a heat‐processed Gynostemma pentaphyllum extract, on body weight, fat loss, and metabolic markers of Korean participants in a 12‐week, randomized, double‐blind, placebo‐controlled clinical trial.

Design and Methods: Obese participants (BMI ≥ 25 kg m−2 and WHR ≥ 0.90 for male or WHR ≥ 0.85 for female) who had not been diagnosed with any disease and met the inclusion criteria were recruited for this study. The 80 subjects were randomly divided into actiponin (n = 40, 450 mg day−1) and placebo (n = 40) groups. Outcomes included measurement of efficacy (abdominal fat distribution, anthropometric parameters, and blood lipid profiles) and safety (adverse events, laboratory test results, electrocardiogram data, and vital signs).

Results: During 12‐week of actiponin supplementation, total abdominal fat area, body weight, body fat mass, percent body fat, and BMI were significantly decreased (P = 0.044, P < 0.05, P < 0.0001, P < 0.0001, and P < 0.05, respectively) in the actiponin group compared to the placebo group. No clinically significant changes in any safety parameter were observed.

Conclusion: Our study revealed that actiponin is a potent antiobesity reagent that does not produce any significant adverse effects. These results suggest that actiponin supplementation may be effective for treating obese individuals.

Source: Soo‐Hyun Park Tae‐Lin Huh Sun‐Young Kim Mi‐Ra Oh P.B. Tirupathi Pichiah Soo‐Wan Chae Youn‐Soo Cha. “Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): A randomized, double‐blind, placebo‐controlled trial.” Obesity (2013), Volume 22, Issue 1.

Heat-processed Gynostemma pentaphyllum extract improves obesity in ob/ob mice by activating AMP-activated protein kinase

Abstract

Gynostemma pentaphyllum is widely used in Asian countries as a herbal medicine to treat dyslipidemia, type 2 diabetes and inflammation. An ethanol extract of G. pentaphyllum lessened obesity by activating AMP-activated protein kinase (AMPK). The levels of damulins A and B, components responsible for AMPK activation in the extract, were increased by autoclaving in a time-dependent manner. Heat-processed G. pentaphyllum extract, actiponin containing damulins A (0.93 %, w/w) and B (0.68 %, w/w), significantly stimulated fat oxidation and glucose uptake via AMPK activation in L6 myotube cells. Oral administration of actiponin to ob/ob mice for 8 weeks decreased body weight gain, liver weight, and blood cholesterol levels with AMPK activation in the soleus muscle. Our results demonstrate the beneficial effect of G. pentaphyllum on improving obesity and have elucidated the underlying molecular mechanisms.

Source: Gauhar R, Hwang SL, Jeong SS, Kim JE, Song H, Park DC, Song KS, Kim TY, Oh WK, Huh TL. “Heat-processed Gynostemma pentaphyllum extract improves obesity in ob/ob mice by activating AMP-activated protein kinase.” Biotechnol Lett. (2012);34(9):1607–16.

New dammarane-type glucosides as potential activators of AMP-activated protein kinase (AMPK) from Gynostemma pentaphyllum

Abstract

AMP-activated protein kinase (AMPK) is a key sensor and regulator of glucose, lipid, and energy metabolism throughout the body. Activation of AMPK improves metabolic abnormalities associated with metabolic diseases including obesity and type-2 diabetes. The oriental traditional medicinal herbal plant, Gynostemma pentaphyllum, has shown a wide range of beneficial effects on glucose and lipid metabolism. In this study, we found that G. pentaphyllum contains two novel dammarane-type saponins designated as damulin A (1), 2α,3β,12β-trihydroxydammar-20(22)-E,24-diene-3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside], and damulin B (2), 2α,3β,12β-trihydroxydammar-20,24-diene-3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside], that strongly activate AMPK in cultured L6 myotube cells. Damulins A and B also increased β-oxidation and glucose uptake with increasing GluT4 translocation to the plasma membrane in L6 myotube cells. Taken together our results indicate that activation of AMPK by damulins A and B may contribute to beneficial effect of G. pentaphyllum on glucose and lipid metabolism.

Source: Nguyen PH, Gauhar R, Hwang SL, Dao TT, Park DC, Kim JE, Song H, Huh TL, Oh WK. “New dammarane-type glucosides as potential activators of AMP-activated protein kinase (AMPK) from Gynostemma pentaphyllum.” Bioorg Med Chem. (2011);19(21):6254–60.

Ginseng

Effect of Korean Red Ginseng in individuals exposed to high stress levels: a 6-week, double-blind, randomized, placebo-controlled trial

Abstract

Background: To investigate the neurobiological evidence supporting the adaptogenic effects of Korean Red Ginseng in reducing the harmful consequences of stress using a double-blind, placebo-controlled trial.

Method: Sixty-three subjects with high stress levels were randomized to receive an orally administered, double-blind, 6-week treatment with Korean Red Ginseng (n = 32) or placebo (n = 31). All participants underwent a comprehensive psychological evaluation using Beck Depression Inventory and Stress Response Inventory, cognitive evaluation using the continuous performance test, biological evaluation by measuring blood levels of lipids, catecholamines, inflammation markers, and heart rate variability at baseline and after 6 weeks.

Results: At baseline, both groups showed no significant differences in age, sex, years of education, Beck Depression Inventory, and Stress Response Inventory. After 6 weeks, triglyceride levels were significantly increased within the normal limit in theKorean Red Ginseng group (F = 4.11, p = 0.048), and the epinephrine level was decreased in this group (F = 4,35, p = 0.043). The triglyceride increase was significantly associated with epinephrine decrease (B = −0.087, p = 0.041), suggesting that Korean Red Ginseng may stabilize the sympathetic nervous system. In addition, we detected a significant group by time effect in the visually controlled continuous performance test, suggesting positive effects of Korean Red Ginseng on cognition.

Conclusion: Korean Red Ginseng might help to stabilize the sympathetic nervous system and improve cognition in individuals with high stress.

Source: Yoon Heo, Maurizio Fava, David Mischoulon, Kwan WooChoi, Eun JinNa, Hana Cho, Hong JinJeon. “Effect of Korean Red Ginseng in individuals exposed to high stress levels: a 6-week, double-blind, randomized, placebo-controlled trial.” Journal of Ginseng Research (2019), Volume 43, Issue 3.

Beet Root

Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite

Abstract

Diets rich in fruits and vegetables reduce blood pressure (BP) and the risk of adverse cardiovascular events. However, the mechanisms of this effect have not been elucidated. Certain vegetables possess a high nitrate content, and we hypothesized that this might represent a source of vasoprotective nitric oxide via bioactivation. In healthy volunteers, approximately 3 hours after ingestion of a dietary nitrate load (beetroot juice 500 mL), BP was substantially reduced (Delta(max) -10.4/8 mm Hg); an effect that correlated with peak increases in plasma nitrite concentration. The dietary nitrate load also prevented endothelial dysfunction induced by an acute ischemic insult in the human forearm and significantly attenuated ex vivo platelet aggregation in response to collagen and ADP. Interruption of the enterosalivary conversion of nitrate to nitrite (facilitated by bacterial anaerobes situated on the surface of the tongue) prevented the rise in plasma nitrite, blocked the decrease in BP, and abolished the inhibitory effects on platelet aggregation, confirming that these vasoprotective effects were attributable to the activity of nitrite converted from the ingested nitrate. These findings suggest that dietary nitrate underlies the beneficial effects of a vegetable-rich diet and highlights the potential of a "natural" low cost approach for the treatment of cardiovascular disease.

Source: Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, Rashid R, Miall P, Deanfield J, Benjamin N, MacAllister R, Hobbs AJ, Ahluwalia A. “Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite.” Hypertension (2008) ;51(3):784–90.

Pomegranate

Beneficial effects of dried pomegranate juice concentrated powder on ultraviolet B-induced skin photoaging in hairless mice

Abstract

The present study investigated the anti-aging effects of pomegranate juice concentrated powder (PCP) in hairless mice following 15 weeks of UVB irradiation (three times a week; 0.18 J/cm²). Skin moisturizing effects were evaluated through skin water, collagen type I and hyaluronan contents, as well as collagen type I and hyaluronan synthesis-related transcript levels. Wrinkle formation and edema scores (skin weights) were also assessed, along with skin matrix metalloproteinase (MMP)-1, MMP-9 and MMP-13 transcript levels. To determine the anti-inflammatory effects of PCP, myeloperoxidase (MPO) activity, interleukin (IL)-1β and IL-10 contents were observed. Caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) were used as an apoptotic index in epidermal keratinocytes. To determine the anti-oxidative effects of PCP, nitrotyrosine and 4-hydroxynonenal immunoreactive cells were detected and glutathione (GSH) content, malondialdehyde levels, superoxide anion production, Nox2, and GSH reductase mRNA expression were all measured. The results indicated that skin wrinkles induced by photoaging were significantly reduced by PCP, whereas skin water contents, collagen type I and hyaluronan contents all increased. Furthermore, IL-1β levels in the PCP-treated groups were lower than those in the UVB-exposed control group. UVB-induced GSH depletion was also inhibited by PCP. Taken together, the results of the current study suggest that PCP has favorable protective effects against UVB-induced photoaging through anti-apoptotic effects, MMP activity inhibition and ECM (COL1 and hyaluronan) synthesis-related moisturizing, anti-inflammatory and anti-oxidative effects.

Source: Kang, S. J., Choi, B. R., Kim, S. H., Yi, H. Y., Park, H. R., Song, C. H., Ku, S. K., & Lee, Y. J. “Beneficial effects of dried pomegranate juice concentrated powder on ultraviolet B-induced skin photoaging in hairless mice.” Experimental and therapeutic medicine (2017), 14(2), 1023–1036.

Blueberry

A Randomized, Double-Blinded, Placebo-Controlled Study to Compare the Safety and Efficacy of Low Dose Enhanced Wild Blueberry Powder and Wild Blueberry Extract (ThinkBlue™) in Maintenance of Episodic and Working Memory in Older Adults

Abstract

Previous research has shown beneficial effects of polyphenol-rich diets in ameliorating cognitive decline in aging adults. Here, using a randomized, double blinded, placebo-controlled chronic intervention, we investigated the effect of two proprietary blueberry formulations on cognitive performance in older adults; a whole wild blueberry powder at 500 mg (WBP500) and 1000 mg (WBP1000) and a purified extract at 100 mg (WBE111). One hundred and twenty-two older adults (65–80 years) were randomly allocated to a 6-month, daily regimen of either placebo or one of the three interventions. Participants were tested at baseline, 3, and 6 months on a battery of cognitive tasks targeting episodic memory, working memory and executive function, alongside mood and cardiovascular health parameters. Linear mixed model analysis found intervention to be a significant predictor of delayed word recognition on the Reys Auditory Verbal Learning Task (RAVLT), with simple contrast analysis revealing significantly better performance following WBE111 at 3 months. Similarly, performance on the Corsi Block task was predicted by treatment, with simple contrast analysis revealing a trend for better performance at 3 months following WBE111. Treatment also significantly predicted systolic blood pressure (SBP) with simple contrast analysis revealing lower SBP following intervention with WBE111 in comparison to placebo. These results indicate 3 months intervention with WBE111 can facilitate better episodic memory performance in an elderly population and reduce cardiovascular risk factors over 6 months.

Source: Whyte, A. R., Cheng, N., Fromentin, E., & Williams, C. M. “A Randomized, Double-Blinded, Placebo-Controlled Study to Compare the Safety and Efficacy of Low Dose Enhanced Wild Blueberry Powder and Wild Blueberry Extract (ThinkBlue™) in Maintenance of Episodic and Working Memory in Older Adults.” Nutrients (2018), 10(6), 660.

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