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Focus & attentionEnhanced cognitive function through blood flow · 4-8 weeks
Too few graded studies1 study
Skin healthProtects against UV damage and improves skin hydration · 4-8 weeks
Too few graded studies1 study
Men's vitalityErectile function via nitric oxide · 4-8 weeks
Too few graded studies1 study
Therapeutic & clinical
Too few graded studies1 study
By the numbers
Pulled from 27 studies with measurable effects
Likely real effects
50%
across studies
People studied
26k
typical study: 512 people
Strongest designs
32
19 pooled, 13 randomised
Showed benefit
75%
9/12 studies
How long studies ran
1–4 weeks
1
1–3 months
2
3+ months
2
Populations Studied
Adults2
Cardiometabolic syndrome patients1
Children and adolescents with ADHD1
Patients with venous insufficiency1
Active research area
16 studies in the last 5 years · Latest meta-analysis: 2025
200520152025
1Cardiometabolic risk factorsMeta-AnalysisCited 6×n=1,685 · large study2025
Supplementation with PBE may ameliorate specific cardiometabolic risk factors, as indicated by reductions in body weight, DBP, SBP, FBS, LDL, and HbA1c levels.
Mohammadi S et al. · BMC complementary medicine and therapies (2025)
Supplementation with PBE may ameliorate specific cardiometabolic risk factors, as indicated by reductions in body weight, DBP, SBP, FBS, LDL, and HbA1c levels.
This approach can be regarded as an adjunct therapeutic strategy for CMS management.
Further high-quality trials with larger sample sizes and longer durations are required to validate these findings.
2ADHD symptom improvement with antioxidantsMeta-AnalysisCited 5×n=3,650 · very large study2024
The rankings of safety and efficacy of the 12 antioxidants vary.
Zhou P et al. · PloS one (2024)
The rankings of safety and efficacy of the 12 antioxidants vary.
Due to the low methodological quality of the included studies, the probability ranking cannot fully explain the clinical efficacy, and the results need to be interpreted with caution.
More high-quality studies are still needed to verify our findings.
4Adverse eventsMeta-AnalysisCited 47×n=7,690 · very large study2020
There is moderate-certainty evidence that phlebotonics probably reduce oedema slightly, compared to placebo; moderate-certainty evidence of little or no difference in QoL; and low-certainty evidence that these drugs do not influence ulcer healing.
Martinez-Zapata MJ et al. · The Cochrane database of systematic reviews (2020)
Noticeable harm
← WorseNo effectBetter →
Pooled data suggest that phlebotonics probably increase adverse events slightly, compared to placebo (RR 1.14, 95% CI 1.02 to 1.27; 37 studies; 5789 participants; moderate-certainty evidence).
There is moderate-certainty evidence that phlebotonics probably reduce oedema slightly, compared to placebo; moderate-certainty evidence of little or no difference in QoL; and low-certainty evidence that these drugs do not influence ulcer healing.
Moderate-certainty evidence suggests that phlebotonics are probably associated with a higher risk of adverse events than placebo.
5HbA1c reductionMeta-AnalysisCited 26×n=1,641 · large study2020
Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible.
Robertson NU et al. · The Cochrane database of systematic reviews (2020)
No clear effect
← WorseNo effectBetter →
In a mixed group of participants with type 1 and type 2 DM we do not know whether pine bark extract decreases HbA1c (MD -0.20 %, 95% CI -1.83 to 1.43; one study; 67 participants; very low-certainty evidence).
We do not know whether pine bark extract increases bone alkaline phosphatase in post-menopausal women with osteopenia (MD 1.16 ug/L, 95% CI -2.37 to 4.69; one study; 40 participants; very low-certainty evidence).
Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible.
6HDL cholesterol increaseMeta-AnalysisCited 12×n=1,065 · large study2019
Since there are few phytochemicals that have a significant increasing effect on HDL-C levels, pycnogenol may have important role in prevention of cardiovascular diseases.
Hadi A et al. · Phytotherapy research : PTR (2019)
Noticeable benefit
← WorseNo effectBetter →
Likely real
To estimate the effect size, changes in blood lipids were implemented.
A systematic review and meta-analysis of 14 clinical trials with 1,065 participants suggested a significant increase in plasma concentration of high density lipoprotein cholesterol (HDL-C; 3.27 mg/dL; 95% CI [0.19, 6.36]; p = 0.038).
Since there are few phytochemicals that have a significant increasing effect on HDL-C levels, pycnogenol may have important role in prevention of cardiovascular diseases.
8Orgasmic function in male anorgasmiaSystematic Reviewn=234 · medium study2025
Pharmacological therapy with cabergoline, yohimbine, bupropion, and pycnogenol can have a positive effect on the orgasmic function of patients with primary or secondary anorgasmia.
Gómez-Bueno MP et al. · Actas urologicas espanolas (2025)
Huge benefit
← WorseNo effectBetter →
The cabergoline improved orgasm in 66% of the population and yohimbine in 55%.
Pharmacological therapy with cabergoline, yohimbine, bupropion, and pycnogenol can have a positive effect on the orgasmic function of patients with primary or secondary anorgasmia.
10Sexual function in erectile dysfunctionMeta-AnalysisCited 5×n=184 · medium study2023
These results indicate that the combination of PAL may have a significant effect on improving sexual function in patients with mild to moderate ED.
Tian Y et al. · Frontiers in endocrinology (2023)
These results indicate that the combination of PAL may have a significant effect on improving sexual function in patients with mild to moderate ED.
This study will provide clinicians with more options for treating patients with ED.
More randomized controlled trials are needed in the future to further demonstrate the effect of combination therapy on sexual function in patients with ED.
Further, high quality randomized clinical trials are needed to confirm this result.
Pourmasoumi M et al. · Phytotherapy research : PTR (2020)
Pooled analysis suggested that pycnogenol supplementation can reduced systolic blood pressure (SBP) of (-3.22 mmHg; 95% CI [-5.52, -0.92]) and diastolic blood pressure (DBP; -1.91 mmHg; 95% CI [-3.64, -0.18]).
Effect of pycnogenol on SBP was more pronounce in subgroup in which pycnogenol was administered along with other treatments.
A significant effect of pycnogenol on DBP in studies with >12-week duration, whereas this favorable effect was not observed in subgroup with ≤12-week supplementation.
Currently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients.
Crawford C et al. · Pain medicine (Malden, Mass.) (2019)
Currently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients.
Until then, providers have the evidence needed to make informed decisions about the safe use of these dietary ingredients, and future research can address existing gaps.
The overall analysis including all trials showed that supplements provided moderate and clinically meaningful treatment effects on pain and function in patients with hand, hip or knee osteoarthritis at short term, although the quality of evidence was very low.
Liu X et al. · British journal of sports medicine (2018)
Another six (undenatured type II collagen, avocado soybean unsaponifiables, methylsulfonylmethane, diacerein, glucosamine and chondroitin) revealed statistically significant improvements on pain, but were of unclear clinical importance.
Chondroitin demonstrated statistically significant, but not clinically important structural improvement (effect size -0.30, -0.42 to -0.17).
The overall analysis including all trials showed that supplements provided moderate and clinically meaningful treatment effects on pain and function in patients with hand, hip or knee osteoarthritis at short term, although the quality of evidence was very low.
18Jetlag following eastbound flightsMeta-AnalysisCited 5×n=10 · very small study2021
Overall, 12 of 183 ingredients contained in 199 products had evidence to support claims.
Chan V et al. · Nutrients (2021)
Large benefit
← WorseNo effectBetter →
Likely real
Meta-analysis (random effects model) indicated melatonin reduced self-reported jetlag following eastbound (n = 5) and westbound (n = 4) flights: standard mean difference -0.76 (95% CI = -1.06 to -0.45, I2 0%, p < 0.00001) and -0.66 (95% CI = -1.07 to -0.26, I2 45%, p = 0.001), respectively.
Pycnogenol also reduced edema scores (n = 3), standard mean -4.09 (95% CI = -6.44 to -1.74), I2 98%, p = 0.0006).
Of the 3842 studies identified, 23 met selection criteria: melatonin (n = 10), Pycnogenol (n = 4), various macronutrients (n = 2), caffeine (n = 2), Centella asiatica (n = 1), elderberry (n = 1), Echinacea (n = 1), fluid (n = 1), and Pinokinase (n = 1).
Additionally, ferulic acid, caffeic acid, and the gut microbial metabolite 5-(3,4-dihydroxyphenyl)-γ-valerolactone (M1) significantly increased in saliva following Pycnogenol® intake.
A correlation analysis revealed a significant inverse association between bleeding on probing and M1 concentration in saliva (r = -0.3476, p = 0.0167).