Pycnogenol

Pycnogenol is a patented formulation of Pine Bark Extract which is standardized to 65-75% Procyanidin compounds by weight. Procyanidins are chain-like structures consisted of catechins similar to some found in green tea (the green tea catechins that do not have 'gallate' in their names). Pycnogenol is similar to grape seed extract and cocoa polyphenols as those are the three most common sources of Procyanidins.

Pycnogenol's benefits include increased blood flow (via a mechanism related to increased nitric oxide levels) and improved blood glucose control. The former exerts cardioprotective effects and may help with erectile dysfunction, while the latter appears to be anti-diabetic.

There are many human trials conducted on Pycnogenol, but a good deal of them have industry funding. (Although industry funding doesn't necessarily invalidate published results, it should always be noted) Althoug the range of Pycnogenol research has signficant breadth, it also has a relative lack of study replication. Some of the studies of pycnogenol in autoimmune disease are also open-label, meaning that neither the researchers nor the subjects are blinded to treatments. While promosing these results need to be interpreted with a degree of caution, since this type of experimental design fails to control for placebo effects or any unconscious bias that may be harbored by researchers analyzing the data. The one topic that appears to have been replicated numerous times is the effects on erectile dysfunction, with the caveat that all of the studies are confounded with the inclusion of l-arginine. So the effects of Pycnogenol alone on erectile dysfunction are still unknown.

Pcyogenol does appear to possess dual anti-oxidant and anti-inflammatory properties, with the latter being confirmed in humans and possibly being subject to a build-up effect over time. The low-dose buildup effect of Pycnogenol as an antiinflammatory agent would make it useful in a multinutrient format, but it may not be the most potent antiinflammatory in isolation. The degree of measured antiinflammatory potential on COX enzymes (targets of Aspirin) are still lower than Aspirin itself.

Although not the most potent anti-inflammatory agent out there, Pycnogenol has shown some efficacy in alleviating symptoms in patients with autoimmune disease. Although the type of rampant inflammation during a flare far-exceeds the ability of pycnogenol, it has shown some efficacy for patients in remission phases of their disease, where symptoms tend to be driven by lower-level, chronic inflammation. One preliminary study has shown that pycnogenol may be particularly effective for relieving dry eye/ mouth symptoms associated with Sjorgren’s syndrome, a common autoimmune condition in women.

Although doses in the range of 40-60mg have been noted to be effective over a prolonged period of time, standard doses of Pycnogenol appear to be in the range of 100-200 mg per day.

Studies have used twice daily dosing (dividing the daily total into two even doses to be taken with breakfast and dinner) as well as once daily dosing with breakfast. Both dosing strategies appear to be effective although they haven't been directly compared. It can be asborbed equally well when taken with or without food.

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects pycnogenol has on your body, and how strong these effects are.

Grade	Level of Evidence [show legend]
	Robust research conducted with repeated double-blind clinical trials
	Multiple studies where at least two are double-blind and placebo controlled
	Single double-blind study or multiple cohort studies
	Uncontrolled or observational studies only

Level of Evidence ? The amount of high quality evidence. The more evidence, the more we can trust the results.	Outcome	Magnitude of effect ? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.	Consistency of research results ? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.	Notes
	Blood Flow	Notable	Very High See all 3 studies	An improvement in nitric oxide dependent blood flow appears to occur following procyanidin supplementation which has been noted in both unhealthy persons as well as healthy controls; there does not appear to be a per se hypotensive effect either.
	Blood Pressure	Minor	High See all 4 studies	Pycnogenol has shown mixed effects on blood pressure in hypertensive subjects. While the majority of trials examined reported modest blood-pressure lowering effects, one randomized controlled trial found no effect on blood pressure. The mixed results suggest that pycnogenol blood-pressure lowering effects may be dependent on the underlying cause of hypertension. More research is needed to determine which individuals with hypertension may benefit from supplementation.
	Leg Swelling	Notable	Very High See 2 studies	Appears to reduce leg swelling secondary to the enhancement of blood flow. While the evidence is not overly robust, it is comparable if not better than the reference supplement of Horse Chestnut
	Symptoms of Osteoarthritis	Notable	Very High See 2 studies	The preliminary evidence at this point in time (promising and independent, but limited) support the usage of pycnogenol in reducing all symptoms of osteoarthritis, reaching up to a halving of symptoms but requiring 90 days for effects to occur
	Asthma	Minor	Very High See 2 studies	A slight reduction in asthmatic symptoms has been noted with Pycnogenol supplementation
	Attention	Minor	- See study	An improvement in attention has been noted, possibly secondary to improvements in general cognition, in students during prolonged academic testing
	Cognition	Minor	- See study	An improvement in cognitive function has been noted in students during academic testing
	General Oxidation	Minor	Very High See 2 studies	A reduction in general oxidation is noted following prolonged Pycnogenol supplementation
	LDL-C	Minor	Very High See all 3 studies	May reduce LDL cholesterol for as long as pycnogenol is taken (some evidence to suggest a normalization after supplement cessation)
	Pain	Minor	- See study	A reduction in pain secondary to improvements in symptoms of osteoarthritis has been noted, and while notable in this certain instance it is not certain if there are inherenet analgesic effects
	Skin Elasticity	Minor	- See study	An improvement in skin elasticity has been noted with Pycnogenol supplementation
	Skin Quality	Minor	- See study	Oral supplementation of standard doses of procyanidins can improve skin quality in elderly women, other demographics not tested
	Subjective Well-Being	Minor	- See study	An increase in well being and mood has been noted in students undergoing academic testing, which correlated with improved test scores
	Symptoms of Menopause	Minor	- See study	A decrease in some symptoms of menopause has been noted with Pycnogenol supplementation
	Blood Glucose	-	- See 2 studies
	C-Reactive Protein	-	- See study	No significant alterations in C-Reactive protein noted
	Endothelin-1	-	- See 2 studies
	HbA1c	-	- See 2 studies
	Heart Rate	-	- See study	No significant alterations in heart rate noted
	Inflammation	-	Very High See 2 studies	No significant influence on standard inflammatory cytokines
	Nitric Oxide	-	- See study	Despite one study establishing the blood flow effects are dependent on nitric oxide, there do not appear to be any significant differences in nitric oxide quantities in saliva
	Chronic Venous Insufficiency	Notable	Very High See 2 studies	Reduces symptoms of chronic venous insufficiency. Potentially useful as an adjunct to compression therapy.
	Erections	Minor	- See study	May be proerectile in persons with organic erectile dysfunction (due to poor blood flow)
	HDL-C	Minor	Moderate See 2 studies	May increase HDL cholesterol, but has mixed evidence to support it and may be unreliable
	Irritable Bowel Syndrome	Minor	- See study	One open-label study (lacks blinding for investigators or subjects and no placebo-control) indicated that pynogenol efficacy for IBS symptoms was on par with some of the common pharmacological antispasmodic agents. Although the study design was weak, other studies demonstrating that pycnogenol has a relaxing effect on intestinal smooth muscle tissue lends some increased confidence that it may also be effective as a treatment for IBS.
	NF-kB Activity	Minor	- See study	A decrease in nF-kB activity has been confirmed in humans given 200mg pycnogenol daily for five days, to the degree of around 15%
	Total Cholesterol	Minor	Moderate See 2 studies	Possible cholesterol lowering effects of small magnitude, but these are not wholly reliable
	Insulin	-	- See study
	Insulin Secretion	-	- See study
	Triglycerides	-	- See study	No significant alterations on triglycerides

Studies Excluded from Consideration

• Confounded with other components as a 'anti-oxidant' supplement^[1]