Oligonol® Clinical Evidence

Metabolic Syndrome | Visceral Fat

Journal of Functional Foods
Nishihira J., et al. Amelioration of Abdominal Obesity by LowMolecular-Weight Polyphenol (Oligonol) from Lychee.
2009;1(4): 341–348

Topic
Can Oligonol® have an effect on metabolic syndrome by reducing visceral fat obesity?

Background
It has been reported that adipocytes (fat cells) generate reactive oxygen species (ROS), and that the increased oxidative stress in adipocytes might be a cause of obesity-associated metabolic syndrome. Previous research provides evidence that polyphenols could improve obesity, lipid metabolism and glucose metabolism.

Study Type
Human clinical intervention trial Study Design Randomized double-blind, placebo-controlled: Participants took either Oligonol® or placebo twice a day for 10 weeks. Physical and hematological examinations as well as CT scan of abdomen were carried out at baseline (control) and after 10 weeks.

Subjects
14 male, 4 female volunteers with abdominal circumference over 85 cm

Dosage
100 mg Oligonol®

Results
Oligonol® supplementation resulted in the following significant changes compared with control: • Decrease in body weight, abdominal circum-ference and visceral fat. • Improved insulin resistance was improved by Oligonol® in conjunction with elevation of serum adiponectin, a hormone that is an independent risk factor for metabolic syndrome.

Conclusion
“These results suggest that Oligonol® ameliorates metabolic syndrome by reducing visceral fat obesity.”

Metabolic Syndrome Cardiovascular & Peripheral Circulation

Natural Medicine Journal Kitadate K, Aoyagi K, Homma K. Effect of Lychee Fruit Extract (Oligonol) on Peripheral Circulation, a Pilot Study Skin Thermography Demonstrates Vasodilation Effects of Polyphenol. 2014 July; 6(7)

Topic
What is the effect of Oligonol on peripheral circulation measured as skin temperature changes by infrared thermography?

Background
A trial to assess the effect of Oligonol on peripheral circulation was compared with a placebo in healthy adults. The underlying mechanism for Oligonol’s effect on circulation may be a result of increased nitric oxide (NO) production. Previous studies have indicated that polyphenols might regulate NO production by the protein kinase C-dependent nicotinamide adenine dinucleotide phosphateoxidase activation pathway. A NO-dependent mechanism is further supported by the previous finding that Oligonol enhanced NO production by regulating phosphorylation and dephosphorylation of endothelial NO synthase (eNOS) 28. The effect of Oligonol on NO production was investigated in bradykinin-stimulated vascular endothelial cells under high-glucose conditions. Oligonol prevented the impairment of eNOS activity induced by high glucose through reversing altered eNOS phosphorylation status. Briefly, when endothelial cells were stimulated by bradykinin (30 nm) and cultured in a medium with a high concentration of glucose, NO production was decreased. However, the reduction was recovered by treatment with Oligonol.

Study Type
A single-blind, placebo-controlled crossover human intervention trial

Study Design
The effect of Oligonol on peripheral circulation was measured as skin temperature changes by infrared thermography. Six healthy subjects (3 male, 3 female; 28–40 years old; body mass index < 25) were supplemented with 50 mg of Oligonol and a placebo (malt extract, dextrin) alternatively on different days. Subjects fasted for 12 hours prior the test and changed into clothing designed for skin thermography measurement. Subjects were asked to stay calm and rest for 60 minutes in a temperature-controlled room (room temperature 26° C ± 1° C, humidity 50%) prior to oral administration of the samples. Thermographic measurements of changes in skin temperature were completed immediately before the oral dose and every 30 minutes after for up to 120 minutes. The areas of interest for the thermographic measurements were the neck, shoulder, and right palm. A paired t-test was used to determine skin temperature differences within subjects between time periods. Welch’s t-test was used to compare skin temperature between groups. A level of p = .05 was recognized as statistically significant. Values are presented as mean and standard error of the mean.

Subjects
Six healthy subjects (3 male, 3 female; 28–40 years of age)

Dosage
50 mg Results Thirty minutes following Oligonol ingestion, thermographic measurements showed a significant temperature increase in the right palm in the Oligonol group compared with the placebo group. Temperature changes between groups were significantly different at 30 minutes and 60 minutes. The temperature remained significantly above base line levels for up to 120 minutes in the Oligonol group. While thermographic measurements of the neck and shoulder trended toward an increase in temperature in the Oligonol group compared with placebo, there were no significant differences between groups. Within each treatment group, the temperature increased and remained significantly above the base line temperature through 120 minutes. The results showed a significant elevation of body surface temperature in the beforeand-after thermographs in the palms of all subjects in the Oligonol group, which suggests peripheral blood flow improvement in healthy people. The results of thermographic measurements of the neck and shoulder showed no significant differences between groups. However, there was a significant increase in both groups compared with the base line.

Conclusion
Oligonol improves peripheral circulation as measured by skin temperature changes using infrared thermography. The elevation in temperature is thought to be a result of the increase of the blood through the vascular smooth muscle, resulting from polyphenol-enhanced NO production in the vascular endothelium. This mechanism may underlie the beneficial vascular health effects of Oligonol. Further studies with increased sample size are warranted.

Unpublished Study
Effect of Oligonol in Increasing Peripheral Body Temperature.
Amino Up Chemical Co., Ltd., Japan,
R & D Division. 2007

Topic
Can Oligonol® increase peripheral body temperature?

Background
People suffering from cold hands and feet are more likely individuals with some kind of blood circulation disorder.

Study Type
Human intervention trial

Study Design
Cross-over study: Thermographic measurements to measure changes in skin temperature were performed on subjects before supplementation with Oligonol® and 30, 60, 90 and 120 minutes following supplementation.

Subjects
5 healthy sedentary male volunteers

Dosage
50 or 100 mg Oligonol® Results Thermographic measurements verified an increase of peripheral
body temperature 30 minutes after intake of 50 or 100 mg Oligonol® and lasting for more than 2 hours.

Conclusion
“This study suggests that a dose of 50 mg of Oligonol® might have improving effects on blood circulation.”

Metabolic Syndrome | Hyperglycemia

Presented at the 4th International Conference on Polyphenols and Health (ICPH2009)
Nishihira J., et al. Effect of Lychee-Derived Low-Molecular-Weight Polyphenol (Oligonol) on Post-Prandial Hyperglycemia.

Topic
Can Oligonol® suppress or moderate excessive elevation of blood glucose levels after a meal?

Background
Post prandial hyperglycemia is recognized as a cardiovascular risk factor in both diabetic and the general population. Animal studies have suggested that Oligonol® has a potential to suppress postprandial hyperglycemia.

Study Type
Human intervention trial

Study Design
Randomized double-blind, placebo controlled crossover: Subjects were supplemented with Oligonol® or placebo prior to food intake. Blood glucose was measured before and after food intake and every 30 minutes for 2 hours.

Subjects
12 male volunteers with fasting blood sugar more than 100 mg/dl

Dosage
600 mg Oligonol®`

Results
Oligonol® supplementation resulted in:
• No side effects, such as abdominal discomfort or diarrhea.
• Suppression or delay of peak glucose level, in 4 cases out of 6.
• Minimal change of blood glucose level in 1 case.
• Increase of blood glucose level in 1 case.

Conclusion
“Oligonol® suppressed, but not in all cases,
postprandial hyperglycemia. From current data and published literatures, it is assumed that Oligonol® may
function as α-glucosidase inhibitor and/or α-amylase inhibitor. The current results encourage us to proceed to further
studies on this effect of Oligonol® on border-line diabetic subjects.”

Metabolic Syndrome Hyperlipidemia

Presented at 15th International Symposium on Atherosclerosis Tani M., et al.
Effect of Lychee Polyphenol on Postprandial Serum Lipid Responses in Healthy Human Subjects.
June 2009

Topic
Can Oligonol® reduce postprandial hyperlipidemia in healthy individuals?

Background
Post prandial hyperlipidemia is recognized as a cardiovascular risk factor in both diabetic and the general population. Animal studies have suggested that Oligonol® has a potential to suppress postprandial hyperlipidemia.

Study Type
Human intervention trial Study Design Three-way cross-over study: Subjects ingested 15 grams of mayonnaise with and without lychee fruit polyphenols (LFP) or oligomerized lychee fruit polyphenols (OLFP). Fasting and postprandial triglycerides (TG) and cholesterol concentrations were measured, as well as serum remnant-like particle cholesterol (RLPC), apolipoprotein B48 (ApoB48) and free fatty acid concentrations (FFA)

Subjects
9 healthy male volunteers

Dosage
500 mg lychee fruit polyphenols or 500 mg oligomerized lychee fruit polyphenols

Results
LFP and OLFP supplementation following fat load resulted in the following changes compared with control:
• Lower serum TG response to fat load.
• Significant decreased chylomicron TG response.
• The time for reaching maximum level of serum TG, chylomicron TG, RLP-C and ApoB48 was delayed.

Conclusion
“This study indicated that lychee polyphenol supplementation could inhibit the fat
absorption and improve postprandial hyperlipidemia in healthy subjects.”

Metabolic Syndrome Atherosclerosis

Presented at the 18th International Congress on Nutrition and Integrative Medicine (ICNIM)
Kishimoto Y., et al. The Inhibitory Effect of Oligonol on MMP Activation.
July 2010

Topic
Does Oligonol® supplementation affect MMP activity following fat intake?

Background
Matrix metalloproteinase (MMP) plays an important role in the initiation and progression of atherosclerosis.

Study Type
Human intervention trial

Study Design
Three-way crossover: Subjects ingested 15 grams of mayonnaise with or without lychee fruit polyphenols (LFP) or Oligonol®. Plasma MMP-2 activity was measured following food intake.

Subjects
9 healthy male volunteers

Dosage
500 mg Oligonol® or 500 mg LFP Results Oligonol® significantly suppressed postprandial MMP-activation.

Conclusion
“This study suggested that Oligonol® might play a preventative role in atherosclerosis
because of the inhibition effects on MMP activation.

Presented at the 18th International Congress on Nutrition and Integrative Medicine (ICNIM)
Tani M., et al. Effect of Oligonol on Risk Factors in Atherosclerosis

Topic
Can Oligonol® supplementation affect postprandial serum lipid response in healthy individuals?

Background
Postprandial hyperlipidemia and MMP activation play an important role in pathogenesis of atherosclerosis.

Study Type
Human intervention trial

Study Design
Cross-over study: Subjects ingested 15 grams of mayonnaise with or without Oligonol®.
Serum triglyceride (TG) response and MMP-9 activity was measured.

Subjects
9 healthy male volunteers

Dosage
500 mg Oligonol®

Results
Oligonol® supplementation following fat load resulted in the following changes compared with control: • Lower serum TG response to fat load. • Significant decreased chylomicron TG response. • The time for reaching maximum level of serum TG, chylomicron TG, was delayed. • Postprandial MMP activation was suppressed.

Conclusion
“These results suggested that Oligonol® may play a preventative role of atherosclerosis
because of improving postprandial hyperlipidemia.”

Anti-Inflammatory Properties

Journal of Medicinal Foods
Shin Y., et al. Oligonol Supplementation Attenuates Body Temperature
and the Circulating Levels of Prostaglandin E2 and Cyclooxygenase-2
After Heat Stress in Humans.
2013 16(4): 318–23

Topic
What effect does Oligonol supplementation have on circulating levels of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2) enzymes, and body temperature after heat stress in 17 healthy human male volunteers?

Background
Oligonol is an optimized phenolic product containing catechin-type monomers and oligomers (dimers, trimers, and tetramers) of proanthocyanidin that are easily absorbed. Oligonol, a phenolic extract from lychee fruit with green tea polyphenols, has been reported to have antioxidant and anti-inflammatory effects. Supplementation with Oligonol decreases serum concentrations of cortisol, IL-1β, and IL-6, which are fever-related hormones or cytokines released after heat stress, therefore, it is thought that it has an antipyretic or fever-reducing potential. Prostaglandin E2 is the principal mediator of fever and exerts its fever-inducing action by binding to receptors on thermoregulatory neurons in the anterior hypothalamus. PGE2 is formed in most cells from cyclooxygenase-mediated metabolism of arachidonic acid. COX-2 enzymes and production of PGE2 are involved in causing febrile and inflammatory responses. Cytokines are chemical messengers found in the circulation and help mediate fever and inflammation caused by heat stress. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α), are cytokines involved in PGE2 production in response to fever. Transcription factors, such as nuclear factor-kappa β and signal transducer and activator of transcription 3, are activated by these cytokines and lead to the induction of COX-2, which mediates fever production. This study investigated the effect of Oligonol supplementation on circulating levels of inflammatory factors prostaglandin E2 and cyclooxygenase-2. It also checked the body temperature after heat stress in 17 healthy human male volunteers (age range 21.6–22.1 years old). The experiments were performed using a chamber with automated climate control at 26.0° C and a relative humidity of 60%–63.0%.

Study Type
A double-blind crossover-design human intervention study

Study Design
Subjects ingested 100 mg of Oligonol in a beverage or a placebo before half-body immersion into hot water at 42° C for 30 minutes. Tympanic and skin temperatures were measured and mean body temperatures were calculated. Serum concentrations of PGE2 and COX-2 were analyzed before, immediately after, and 60 minutes after immersion in the hot water. All experiments were conducted in a thermoneutral climate chamber (26° C ± 0.5° C, 60% ± 3% relative humidity, and < 1 m/sec air velocity) from 2 to 5 p.m. Upon arrival at the climate chamber, the subjects wore short pants and sat in a chair in a relaxed posture for 60 minutes to become conditioned to the chamber climate before the commencement of the experiments. After 60 minutes of rest, heat load was applied to each subject via immersion of half of their body into a hot water bath of 42º C ± 0.5º C for 30 minutes. Measurements were taken at rest, immediately after immersion, and 60 minutes after.

Subjects
drank 0.5 L of the Oligonol beverage or the placebo beverage 1 hour before the immersion.

Subjects
17 healthy males 21 to 22 years old Dosage 100 mg Results Oligonol intake significantly prevented elevation of tympanic temperature (difference of 0.17° C after heat stress, p < .05; 0.17° C at 60 minutes, p < .05) and mean body temperatures (temperature difference: 0.18° C at post, p < .05; 0.15° C at re-60, p < .05), and lowered concentrations of serum PGE2 (increased by 13.3% vs. 29.6% at post, p < .05) and COX-2 (increased by 15.6% vs. 21.8% at post, p < .05) compared with placebo beverage.

Conclusion
The results suggest that Oligonol suppresses increases in body temperature under heat stress, and this is
associated with decreases in serum levels of the inflammatory mediators PGE2 and COX-2 enzymes.

Anti-Inflammatory Properties Journal of Functional Foods

Moriawaki Y., et al. Effects of Oligonol, an Oligomerized Polyphenol Formulated from Lychee Fruit, on Serum Concentration and Urinary Excretion of Uric Acid. 2010;3(1):13–16

Topic
Does Oligonol® have an effect on uric acid metabolism and therefore be used as an effective treatment or prevention of gout or hyperuricemia? Background High serum uric acid levels lead to an increased risk for gout and epidemiological studies suggest that polyphenols from cherries and those found in wine might play a role in reducing serum concentration of uric acid. High levels of serum uric acid (hyperuricemia) increase the risk for gout.

Study Type
Human clinical intervention trial

Study Design
Open-label controlled: serum uric acid concentration and uric acid excretion were measured at baseline and three more times following Oligonol® supplementation. Subjects served as their own control by repeating the experiment 2 weeks later with no supplementation.

Subjects
6 healthy male volunteers

Dosage
600 mg Oligonol®

Results
Oligonol® supplementation resulted in the following significant changes compared with baseline and compared with control period:
• Decreased serum and urinary uric acid excretion at 0.5, 1.5, and 2.5 hours after administration.
•Fractional uric acid clearance was also decreased over the entire experimental period. In addition, an in vitro
experiment showed that Oligonol® inhibited xanthine oxidase activity in a dosedependent manner.

Conclusion
“Together, these results suggest Oligonol® lowers serum concentration of uric acid through inhibition
of xanthine oxidase, and may be effective for prevention and treatment of hyperuricemia and/or gout.”

Dermatological Benefits

Unpublished Study Clinical Study on the Improvement Effect of Oligonol in Skin.
Amino Up Chemical Co., Ltd., Japan.
January 2007

Topic
Can the oral supplementation of Oligonol® affect the skin?

Background
Antioxidant supplementation has been correlated with improved skin condition due to the ability to prevent free radical damage to skin. Study Type Human intervention trial

Study Design
Open-label controlled: Participants were supplemented with Oligonol® twice per day for 12 weeks. Using a Robo Skin Analyzer, pigment deposits (freckles) and wrinkles in the eye angle were evaluated. In addition, participants responded to a questionnaire regarding their skin condition.

Subjects
17 female volunteers between 26 and 60 years of age.

Dosage
100 mg Oligonol® twice per day

Results
After 12 weeks of supplementation with Oligonol®, the following results were reported:
• Improvement tendency of pigmentary deposits (higher than 10% reduction) in 29% of the subjects.
• Reduction of the skin age (estimated age).
• Improvement tendency of the wrinkles in eye area (higher than 10% reduction) in 47% of cases.
• Results were more visible in participants who were over 40-years-old.
• 50% of participants reported noticeable improvement of skin condition,
especially in reduction of skin roughness and improving wrinkles.

Conclusion
“Based on analysis with Robo Skin Analyzer it was possible to verify an improvement in pigmentary deposits and wrinkles in the eye angle. In addition many responses to the questionnaire expressed improvement of skin condition.”

Presented at the 16th International Congress on Nutrition and Integrative Medicine (ICNIM) Tsuboi T., et al.

Anti-Aging Effect of Novel Low Molecular Polyphenol “Cysteinyl-Oligo-Proanthocyanidin.” August 2008 Topic Can topical application of Oligonol®-CS improve skin parameters associated with aging? Background Polyphenols proved to have antiallergic, antioxidative, antibacterial, and anti viral effects in in-vitro studies, but their high molecular weight made them less penetrable to the skin and cells. Oligonol®-CS contains low molecular weight oligomers, resulting in higher skin permeability.
Study Type
Human intervention trial Study Design Oligonol®-CS solution was used topically twice a day on left half of face, while a placebo was used on right half of face. Skin parameters such as skin elasticity, effect on noticeable pores, pigmentation, moisture and oil content, and wrinkles were measured at baseline and after 2 months.

Subjects
5 volunteers

Dosage
10% Oligonol®-CS

Results
In vivo and in vitro data reported that Oligonol®-CS:
• Possessed strong UV protection activity and antioxidative activity.
• Prevented Maillard reaction and inhibited MMP-1 production which helped protect the collagen and elastin
damage in the skin leading to the improvement of skin wrinkles and skin elasticity.
• Improved wrinkles and pigmentation.
• Reduced skin thickness in Oligonol®-CS applied area compared with placebo. and these results can be
attributed to the improvement of barrier function.
• Noticeably improved pores.
• Contributed strong antioxidative and UV protection resulting in improvement of pigmentation.

Conclusion
“Based on these findings, Oligonol®-CS can be used as an active cosmetic ingredient with various
functional activities for future cosmetic product development.”

The FASEB Journal

Fujii H, MacKenzie AR, Kitadate K. Effects of Oligonol Supplementation on the Appearance of Skin Photo-Aging, Wrinkles, Hyperpigmentation and Lentigines. April 1 2010.

Topic
Can oral supplementation with Oligonol® positively affect the appearance of skin photo-aging, wrinkling,
hyperpigmentation and lentigines (liver spots)?

Background
Oligonol® has well-documented effects on oxidative stress prevention, which can translate directly to skin improvement.

Study Type
Human intervention trial

Study Design
Open-label controlled pilot. Subjects were supplemented with Oligonol® twice daily for 3 months.

Subjects
19 healthy sedentary male volunteers. Various parameters of skin health were performed using high resolution photography (DermaLite) and optical profilometry as well as serum CRP levels (C-reactive protein, an inflammatory marker). Dosage 100 mg Oligonol® twice daily

Results
After 3 months, Oligonol® supplementation resulted in:
• Decreased CRP in 54.5% of participants.
• Decrease in fine lines in 72.7% of participants based on blind evaluation of DermaLite photographs by trained observers.
• Reduction of deep wrinkles and sleep wrinkles in 18.2% of participants.
• Consistent lightening and brightening of complexion, along with less redness, blotchiness, freckles and brown-pigmented blotches.

Conclusion
The outcome confirmed known positive effects to skin health.

Phytotherapy Research

Nishizawa M., et al. Supplementation with a Flavanol-rich Lychee Fruit Extract Influences the Inflammatory Status of Young Athletes.
2011

Topic
Can Oligonol® supplementation have an effect on inflammation and tissue damage in athletes during intense exercise?

Background
Exercise has acute and chronic effects on inflammatory response. These effects can be measured by the release of inflammatory cytokines, such as interleukin (IL)-6. Plasma IL-6 increases during physical exercise and muscle contraction also induces the production of IL-6 as a myokine. Myokines are a subclass of cytokines that are produced, expressed and released by muscle fibers and exert either paracrine or endocrine effects.

Study Type
Human clinical intervention trial

Study Design
Randomized, placebo-controlled double blind: Subjects received 100 mg daily of Oligonol® (50 mg twice per day) or a placebo daily for 2 months. All subjects performed identical high-intensity training for 2 months. A 2-month training program was designed by a qualified trainer and consisted of repeated training and rest cycles with running at low intensity (50%), medium intensity (13%), and high intensity (37%). Each subject ran a total of 800–1000 km during the training period. Various outcome parameters were measured in the morning before training period (baseline), 1 month (mid-training) and 2 months (post-training).

Subjects
20 young male long distance runners

Dosage
100 mg Oligonol®

Results
Two months of Oligonol® supplementation resulted in:
• The resting heart rate was not significantly different between the two groups at baseline. However, the resting heart
rate gradually decreased in the Oligonol® group and was significantly lower post-training than in the placebo group.
• White blood cell count was significantly lower at posttraining in the Oligonol® group than in the placebo group.
• Hemoglobin, hematocrit and mean corpuscular hemoglobin were significantly lower at mid training in the
Oligonol® group than in the placebo group, although significant differences were not observed at post-training.
• The percent decrease in the IL-6 level from pre-training to midtraining (mid/pre) was significantly
smaller in the Oligonol® group than in the placebo group.
• The percent increase of the cytokine TGF-1 from baseline to post training was significantly
greater in the Oligonol® group than in the placebo group.

Conclusion
“Flavanol-rich lychee fruit extract (FRLFE) seems to protect against exercise-induced oxidative stress and
tissue damage and may be useful as a dietary supplement for regular exercisers. Further studies will help us elucidate the
mechanism of action of FRLFE during exercise.”

Athletic Performance

Journal of Clinical Biochemistry and Nutrition Kang S., et al. Oligomerized lychee fruit extract (OLFE) and a mixture of vitamin C and vitamin E for endurance capacity in a double blind randomized controlled trial. 2012; 50(2): 106-113

Topic
Can Oligonol® supplementation have an effect on exercise endurance capacity and how does it compare with vitamin C and E supplementation?

Background
Several studies have presented evidence that exercise can increase Reactive Oxygen Species (ROS) production and that exercise-induced oxidative stress can cause muscle fatigue. While several animal studies have found that antioxidant supplements delay muscle fatigue and improve exercise performance, the clinical efficacy of antioxidants remains uncertain. Study Type Human clinical intervention trial

Study Design
Randomized, placebo-controlled double blind: Subjects received 200 mg daily of Oligonol® (50 mg twice per day), a mixture of 800 mg vitamin C and 320 IU vitamin E, or a placebo daily for 30 days.

Subjects
70 regularly exercising males. Various parameters of exercise endurance were measured at baseline and at the end of 30 days.

Dosage
200 mg Oligonol®

Results
30 days of Oligonol® supplementation resulted in: • Running times to exhaustion at 80% HRmax were measured and the change from baseline to after supplementation increased only in the Oligonol® group. • Endurance capacity was measured by the anaerobic threshold (AT). After supplementation, the Oligonol® group showed a significant increase in their anaerobic threshold, by 7.4% , whereas the vitamin and placebo groups showed no significant changes. • The initially observed increase in lactase dehydrogenase (used to screen for tissue damage) after the treadmill test for the Oligonol® group at baseline was reduced after 30 days of supplementation by over one-fourth of the initial observation.

Conclusion
“The increase in the submaximal running time and the AT, without a change in the VO2max value, and
the decrease in the exercise-induced amplification of the LDH suggest Oligonol® as a possible enhancer of the endurance capacity.

Nutrition Research and Practice
Lee JB., et al. The Effects of Oligonol Intake on Cortisol
and Related Cytokines in Healthy Young Men.
2010; 4(3): 203-207

Topic
Does Oligonol® have an anti-inflammatory effect following exercise-induced stress?

Background
Exercise has acute and chronic effects on systemic immunity and inflammatory response. These effects can be measured by changes in serum levels of the stress hormone cortisol and the release of inflammatory cytokines, such as interleukin (IL)-6 and IL-1β. These responses are remarkably similar to those induced by infection, sepsis, or trauma.

Study Type
Human clinical intervention trial

Study Design
Randomized, placebo-controlled: Each subject received 0.5 L water with Oligonol® or a placebo daily for 4 weeks.
The body composition, white blood cell (WBC) and differential counts as well as the serum cortisol, IL-1β, and IL-6
concentrations were measured before and after Oligonol® intake.

Subjects
19 healthy sedentary male volunteers

Dosage
100 mg Oligonol®

Results
Four weeks of Oligonol® supplementation resulted in:
• Significant decreases in serum cortisol concentration and levels of IL-6 and IL-1β were significantly
decreased with Oligonol® intake compared to before treatment.
• The rate of increase of these factors after exercise was decreased compared with the placebo group.

Conclusion
“These results suggest that oral Oligonol® intake for 4 weeks had a significant effect
on inhibition of inflammatory markers in healthy young men.”

Japanese Journal of Mountain Medicine
Nagasawa J., et al. Oxidative Stress to Acute
Hypobaric-Hypoxia and Antioxidant Ability of Oligonol.
2010; 30:118–124

Topic
Does Oligonol® supplementation have an effect on hypobaric/hypoxic oxidative stress?

Background
Oxidative stress disorders cause or induce various diseases. Oxidative stress is increased during exposure to high altitude/hypoxic environments.

Study Type
Human intervention trial

Study Design
Single-blind, placebo controlled: 2-week supplementation of Oligonol® followed by physical activity under hypobaric/hypoxic stress conditions (616 hPa, 12.8% oxygen). Various parameters of oxidative stress were measured at rest and after exercise at 80% HRmax.

Subjects
10 men

Dosage
200 mg Oligonol®

Results
Following two week supplementation with Oligonol®, the following results were reported:
• Significant increase in plasma erythropoietin and salivary cortisol levels in both placebo and treatment group,
but levels tended to be lower in the Oligonol® group.
• Oligonol® group demonstrated significantly lower levels of serum MDA-LDL concentrations and hydroxyl
radical production levels.

Conclusion
“Antioxidant administration shows significant antioxidant power with exercise load.”

Presented at the 64th the Japanese Society of Physical Fitness and Sports Medicine Kusakabe M., et al.

Effect of Oligonol Supplementation on Oxidative Stress and Antioxidant Capacity Following High-Intensity Intermittent Sprint Cycle Exercise. September 2009
Topic Can Oligonol® supplementation effect oxidative stress and antioxidant capacity following high-intensity exercise?

Background
Increased aerobic metabolism during exercise is a potential source of oxidative stress. Antioxidant supplements
offer protection against the oxidative stress of exercise.

Study Type
Human intervention trial

Study Design
Randomized, placebo-controlled trial: participants were supplemented with either Oligonol® or a placebo for 2 weeks. After 2 weeks, subjects performed intermittent sprint cycle exercise for 20 sets (7-second maximal pedaling with 53 second recovery). Oxygen uptake and heart rate were measured continuously during exercise. Various parameters for oxidative stress were measured before exercise (baseline), immediately after exercise, and again 1 hour after exercise.

Subjects
18 male volunteers

Dosage
200 mg Oligonol®

Results
The following changes were reported in the Oligonol® group compared with placebo group:
• Significant increase in oxygen uptake during exercise.
• Significant decrease in serum LDL concentration.

Conclusion
“Oligonol® supplementation increases oxygen uptake during exercise. It seems likely that supplementation might reduce oxidative stress during rest and exercise in spite of no change in antioxidant capacity.”

Advances in Exercise and Sports Physiology Ohno H., et al.

The Supplementation of Oligonol, the New Lychee Fruit-Derived Polyphenol Converting Into a Low-Molecular Form, Has a Positive Effect on Fatigue During Regular Track-and-Field Training in Young Athletes.
2008; 13(4):93-99

Topic
Can Oligonol® supplementation affect subjective mood states (fatigue and pain) and oxidative stress following athletic training?

Background
Increased aerobic metabolism during exercise is a potential source of oxidative stress. Antioxidant supplements offer protection against the oxidative stress of exercise. In addition, the relationship between training distance and mood has been found to follow a dose-dependent pattern — mood progressively worsening as training load increases.

Study Type
Human intervention trial

Study Design
Randomized Single-Blind placebo-controlled crossover: Subjects were supplemented with either placebo or Oligonol® for 26 days (Period 1). Their supplementation was switched for the next 26 days (Period 2). During the two periods, the training protocol consisted of 3 hour track-and-field training 5 times/week. Subjects completed three questionnaires before training began, and at the end of each period. In addition, urine samples were submitted and various parameters on oxidative stress were measured.

Subjects
24 male and 22 female athletes

Dosage
200 mg Oligonol® Results The following changes were reported for Oligonol® supplementation compared with placebo: • RPE (Ratings of Perceived Exertion) responses during training were significantly lower in both groups, suggesting Oligonol® intake caused the subjects to feel less fatigued. • Tendency to attenuate the feeling of pain (muscular, lumbago and menstrual) followed by a change for the worse for group that discontinued Oligonol® midway through training.

Conclusion
“The results suggest that Oligonol® supplementation in young athletes has significant subjective positive effects particularly on fatigue during training and thus may contribute to the maintenance of good conditioning.”

Athletic Performance

Oligonol Clinical Evidence 11 Oligonol® Clinical Evidence Presented at the 22nd International Congress on
Nutrition and Integrative Medicine (ICNIM) Fujita S., et al. Effect of oligomerized polyphenol supplementation on lipid metabolism during exercise in healthy men. July 2014 Topic What effect does Oligonol given to young men exercising have on plasma growth hormone levels and fat metabolism?

Background
Many studies have shown that oligomerized polyphenol (OLG) supplementation helped reduce abdominal fat in obese people. However, the role of OLG on lipid metabolism during exercise has not been tested. The purpose of this current study was to investigate the effect of an Oligonol supplement on lipid metabolism during aerobic exercise.

Study Type
Human clinical intervention study

Study Design
Oligonol at 100 mg/day and a placebo were given for 14 days in 10 healthy young men using a double-blind, randomized, crossover design. After an overnight fast on the 15th day, an exercise test using 50% V02 max for 30 minutes on a bicycle ergometer was administered. Blood samples taken before, during, and up to 30 minutes after exercise were analyzed for hormones and metabolites.

Subjects
10 healthy young men

Dosage
100 mg a day of Oligonol Results Insulin resistance was assessed by a method known as HOMA-IR and was lower in the Oligonol group compared to the placebo group (p~0.09). Plasma glycerin and free fatty acid concentrations increased significantly 15 to 30 minutes after exercise in the Oligonol group as compared to the placebo group (p<0.05). In addition, the percent change in serum growth hormone was higher in the
Oligonol group compared to the placebo group during exercise (p<0.05).

Conclusion
It was found that 14 days of Oligonol supplementation significantly increased exercise-induced growth
hormone response and resulted in increased lipolysis (fat breakdown) in response to aerobic exercise in young men.

Oral Health

Presented at the 22nd International Congress on Nutrition and Integrative Medicine (ICNIM)
Matsukawa T., et al. Development of Oligonol rich candy and the effect on the oral cavity.
July 2014

Topic
What is the effect of a candy made with Oligonol, a polyphenol-rich extract of lychee fruit, on bad breath
and Candida albicans population in the mouths of human subjects?

Background
A candy has been formulated with a low-molecular-weight proanthocyanidin-type polyphenol derived from lychees and known as Oligonol. It has been proven that this confection can be utilized for preventive and therapeutic use in oral candidiasis models as demonstrated both in vitro and in vivo. Oligonol is formulated as a major component of the candy and has shown antibacterial activity against E. coli, MRSA, C. albicans, etc. This bioactive antimicrobial property is expected to aid in the prevention of oral candidiasis and in the improvement of oral cavity health to reduce the risk of developing periodontitis and milder conditions such as bad breath.

Study Type
Human clinical intervention study Study Design The investigators studied the effect of Oligonol-rich candy, containing a concentration of Oligonol, in the oral cavity in 20 middle-aged and elderly people in good health. Ten subjects consumed 3 Oligonol-rich candies daily for a week, and another 10 subjects consumed placebo candies instead during the same period. Following a 2-week wash-out phase after administration of the test substance, a crossover study was conducted. The study was conducted as a doubleblind test after being approved by an ethics committee. Mouth rinses were collected 4 times before and after each test. Halitosis was measured by hand-held device. A questionnaire was given after each test.

Subjects
20 middle-aged and elderly people in good health

Dosage
Not reported

Results
A comprehensive analysis of the results was created from the total viable bacterial count in the mouth rinse, from the reported degree of halitosis, and from the questionnaire. It was revealed that the Oligonolrich candy significantly decreased the count of C. albicans in live form in the 8 subjects who had more than 4,000 CFU of C. albicans before the study. Bad breath significantly improved for all 20 subjects and the questionnaire results showed that the Oligonol-rich candy improves halitosis and a discomfort index of a “sticky” mouth environment.

Conclusion
The results of this study demonstrate that Oligonolenriched candy is useful for oral hygiene practice in healthy people for daily use.

Bioequivalence of Capsule vs. Liquid Unpublished Study Bioequivalence Study of Oligonol.

Amino Up Chemical Co., Ltd.,
Japan. June 13, 2007

Topic
Is Oligonol® absorbed and does it improve blood antioxidant capacity when ingested orally in hard capsule or dissolved in a drink?

Background
In vitro antioxidant assays cannot be extrapolated to guarantee absorption and improved blood antioxidant capacity. Human clinical trials are required to show bioavailability.

Study Type
Human intervention trial

Study Design
Open-label controlled:

Subjects were divided up into groups by age and various forms of Oligonol® were ingested: 200mg hard capsule with water 200mg hard capsule (intake with black tea) 200mg dissolved in bottled water 200mg dissolved in black tea 200mg dissolved in sports drink 200mg dissolved in carbonated drink Blood samples were taken before the intake, 1, 2, 4, 6 and 8 hours following intake. Total serum polyphenol concentration and serum antioxidant activity by TEAC were measured.

Subjects
34 volunteers

Dosage
200 mg Oligonol®

Results
During the period of the study:
• Serum polyphenol concentration was almost double for Oligonol® dissolved in water compared with hard capsule.
Maximum polyphenol content was reached in 2 hours for both cases.
• Same results were seen with Oligonol® dissolved in black tea versus Oligonol® hard capsule taken with black tea —
almost double the polyphenol concentration of serum, but speed of absorption was the same.
• Oligonol® dissolved in black tea had higher serum polyphenol concentration than other drinks.
• Serum antioxidant activity was 1.5 times higher for Oligonol® taken in dissolved in water compared to hard
capsule taken with water. Tmax was reached in 2 hours for both cases.
• Same results were seen with Oligonol® dissolved in black tea versus Oligonol® hard capsule taken with black tea —
about 1.5 times the serum antioxidant capacity, but speed of absorption was the same.

Antioxidant Properties Polyphenols Communications Hackman R., et al.

Absorption of Flavonols from a Novel Lychee Fruit Extract Rich in Flavonoids, and Effects on Membrane Stability and Oxidant Defense in Experimental Animals and Healthy Human Adults. 2008;2(T5.79)

Topic
Is Oligonol® absorbed and bioavailable and is it more bioavailable than lychee fruit extract (LFE)? Background In order for flavonols to be absorbed, longer-chain flavonols need to be degraded into flavonol monomers or procyanidin dimers, as longer-chain procyanidins appear too large to be absorbed intact. Oligonol® is produced from lychee fruit extract whose procyanidins have been deoligomerized into monomers and dimers.

Study Type
Human intervention trial

Study Design
Randomized parallel group: Participants consumed either unprocessed LFE or Oligonol® as a single dose. Blood was collected at 0, 2, 4, and 6 hours. Participants continued to consume supplements for 90 days and blood was collected again. Total polyphenol content of blood serum was measured.

Subjects
37 healthy volunteers

Dosage
100 mg Oligonol® versus 100 mg LFE Results Serum polyphenol concentration
was significantly higher in Oligonol® group than in LFE group over the 6-hour test period.

Conclusion
“This data supports the concept that appropriately processed lychee fruit extract is well absorbed and may
be useful as a flavonoid-rich dietary supplement.”

Antioxidant Properties Safety Presented

At the 3rd International Conference on Polyphenols and
Health Aoyagi K., et al. Suppressive Effect of Depolymerized Product “Oligonol”
for Reactive Oxygen in Humans.
November 2007

Topic
Does Oligonol® supplementation diminish oxidative stress and is it superior to lychee fruit polyphenols (LFP) in reducing oxidative stress?

Background
Oxidative stress has been thought of as a cause of aging, cancer or vascular disturbance. Creatinine is a physiological substance that distributes almost equally in the body. The oxidative product of creatinine can be measured by hydroxyl radicals (CTLs) in urine, and the ratio between creatol and creatinine is a good marker of oxidative stress.

Study Type
Human clinical intervention trial

Study Design
Two way crossover study. Oxidative stress was measured by creatol/creatinine ratio in plasma at baseline and after 4 hours,
1 month and 3 months following Oligonol® supplementation. Subjects repeated study using lychee fruit polyphenols (LFP).

Subjects
43 healthy volunteers and 12 presymptomatic volunteers (high baseline oxidative stress levels)

Dosage
100, 200 and 400 mg Oligonol® or LFP

Results
Oligonol® supplementation was effective in lowering oxidative stress of initially-high-score subjects. For the initially-low-score subjects, Oligonol® increased oxidative score. Oligonol® had a superior effect compared with LFP.

Conclusion
“Oligonol® may have the oxidative stress-modulating effect by normalizing various statuses of oxidative stress.”

Safety

Spierings E, et al. A Phase I Multiple Dose Trial of the Safety of Oligonol,
a Novel Polyphenol Oligomer, in Healthy Volunteers. 2008

Topic
Is Oligonol® safe for human consumption?

Background
The health claims for functional foods and the identification of their active functional ingredients mandates the documentation of any potential toxicity they may present. Phase 1 clinical trials are used to make the initial safety assessment of compounds with potential medical uses. Study Type Phase I Clinical Trial

Study Design
Open-label controlled: Oligonol® was orally administered to healthy subjects twice per day for 14 days. Its effect on various laboratory parameters assessing safety were measured at 7-day intervals. Adverse events were monitored at 7-day intervals.

Subjects
30 healthy male and female volunteers

Dosage
600 mg Oligonol® (300 mg twice per day)

Results
Laboratory measurements and adverse effects reported after 7 and 14 days of
supplementation with Oligonol®:
• No abnormalities in the laboratory parameters between baseline and the final visit.
• There were no changes in the EKG or in the urine analysis between the visits.
• There was no difference found in serum LPO between baseline and the final visit.
• 21 subjects (70%) reported no adverse symptoms during the trial at the interim or final assessment.
• 3 subjects (10%) had abdominal discomfort and bloating at both interim and final visits, but none dropped out. • 17% of subjects reported other transient symptoms at either the interim or the final visit.

Conclusion
“This data supports previous data in animals and human beings that shows Oligonol® is a safe, well-tolerated nutritional supplement.”

Oligonol 3-month Clinical Safety Study

Amino Up Chemical Co., Ltd.,
Japan

Topic
Is Oligonol® safe for human consumption?

Background
The health claims for functional foods and the identification of their active functional ingredients mandates the documentation of any potential toxicity they may present. Phase 1 clinical trials are used to make the initial safety assessment of compounds with potential medical uses.

Study Type
Safety assessment

Study Design
Open-label: Volunteers were supplemented with 400 mg/day for 92 days. Oligonol® and general blood biochemical analysis
was conducted before intake and at day 30 and day 92. Adverse events were monitored.

Subjects
6 healthy volunteers Dosage 400 mg Oligonol® (200 mg taken twice per day)

Results
During the period of the study:
• No significant adverse event was reported.
• One of the volunteers experienced a transient mild symptom of diarrhea.
This symptom disappeared spontaneously without specific treatment after one week.
Therefore it was determined that it was not related to a side effect.
• The general biochemical analysis showed no adverse event in liver and kidney functions.

Conclusion
“Based on these findings, it can be assumed that Oligonol® is safe as food.” S

Oligonol Intake on Cortisol and Related Cytokines

Lee JB, et al. The Effects of Oligonol Intake on Cortisol and Related Cytokines in Healthy Young Men. 2010; 4(3):203-207.

Topic
Does Oligonol® have an anti-inflammatory effect following exercise induced-stress? 

Background

Exercise has acute and chronic effects on systemic immunity and inflammatory response. These effects can be measured by changes in serum levels of the stress hormone cortisol and the release of inflammatory cytokines, such as interleukin (IL)-6 and IL-1β. These responses are remarkably similar to those induced by infection, sepsis, or trauma.

Study Type
Human clinical intervention trial

Study Design

Randomized, placebo-controlled: Each subject received 0.5 L water with Oligonol® or a placebo daily for four weeks. The body composition, the white blood cell (WBC) and differential counts as well as the serum cortisol, IL-1β, and IL-6 concentrations were measured before and after Oligonol® intake.

Subjects
19 healthy sedentary male volunteers.

Dosage
100 mg Oligonol®

Results

Four weeks of Oligonol® supplementation resulted in:

  • Significant decreases in serum cortisol concentration and levels of (IL)-6 and IL-1β were significantly decreased with Oligonol® intake compared to before treatment
  • The rate of increase of these factors after exercise was decreased compared to the placebo group.

Conculsion 
“These results suggest that oral Oligonol® intake for four weeks had a significant effect on inhibition of inflammatory markers in healthy young men.”

Mechanism of Action

Oligonol has both anti-inflammatory and antioxidant activity, both of which have protective effects on the skin.

The antioxidant polyphenols in Oligonol are effective in neutralizing oxygen radicals that contribute to skin aging. For example, they remove from the bloodstream copper and iron ions involved in hydroxyl radical formation, which increase the formation of age spots.

Additionally, these polyphenols have notable anti-inflammatory activity, reducing UVB-induced cyclooxygenase (COX-2) expression, a major inflammation pathway. (Unchecked inflammation can lead to age-related cell damage.)

Finally, Oligonol polyphenols inhibit various enzymes and metabolic processes that degrade skin, including: 1. The skin matrix enzymes elastase and collagenase responsible for breaking down collagen and elastin and leading to wrinkles, 2. protein glycation, the process whereby proteins bind to sugars, creating advanced glycation end products that cause skin to sag, and 3. melanin production, which is needed for the creation of brown spots.

Mechanism of Action: Weight Management

Oligonol supports weight management efforts, blood sugar control, and cardiovascular health. It both decreases the formation of new visceral fat and helps burn existing fat. It reduces the creation of visceral fat by reducing cortisol, while helping burn fat by regulating the production of hormones produced in fat tissue. Oligonol has also been shown to reduce abdominal circumference and visceral fat through its ability to improve insulin resistance and raise adiponectin, a hormone that increases insulin sensitivity. Oligonol also helps ameliorate metabolic syndrome and atherosclerosis by lowering triglycerides and improving postprandial hyperlipidemia.