Testosterone Erectile Dysfunction Nitric Oxide

When More Testosterone Doesn’t Help Erectile Health – Part 1 of 2

The role of vascular health on male sexual function

“I’m injecting 150 mg of testosterone cypionate every week. I look muscular. I have lots of energy – so much I actually need to take sleeping pills to wind down at night. So why can’t I get a good erection? What is wrong with me?”

I counsel countless men* with stories like this.

Typically, these fellows come to see me after visiting a “Low T” clinic and trying various hormones and hormone precursors. From testosterone creams to shots, to HCG (human chorionic gonadotropin), to breast cancer drugs and beyond, hormone treatments do indeed help some men with erectile dysfunction – but fewer men than you might think.

Erectile dysfunction (ED, impotence) is a fairly common medical condition, characterized by the inability to achieve and maintain a penile erection firm enough for satisfying sexual intercourse.1

I often explain to my clients with ED that testosterone is just one piece of the puzzle. ED can also be caused by dysfunctions in the nervous system (including mental health), in the adrenal glands, in metabolic function, in B vitamin status, and in endothelial health (the inner lining of the blood vessels). The latter is also known as “endothelial ED,” a commonly overlooked aspect of sexual health – and the focus of this article.

40% of men above the age of 40 are now estimated to have some degree of ED.

Although ED is more common among older men,16 it’s becoming more common among younger men as well: 40% of men above the age of 40 are now estimated to have some degree of ED.13 While an estimated 152 million men worldwide had ED in 1995, that number is expected to swell (no pun intended) to over 320 million people by 2025.17,18 It’s no coincidence that heart disease is also on the rise: ED is often a warning sign of impending cardiovascular disease.

The mechanics of erection

Tumescence (penile erection) relies on proper blood flow. During the male sexual response, blood flow into the penis through the arteries increases, as blood flow out of the penile veins decreases.2,3 This process effectively traps blood in the penis, resulting in an erection.

The issue with ED tends to be with the first part of this process – the delivery of blood into the penis. The integrity of the circulatory system – the system of “highways” by which blood circulates throughout the body – is essential for male sexual performance and satisfaction.4

A key component of a healthy circulatory system lies in an important little gas called nitric oxide.

Nitric oxide gets the blood flowing

Nitric oxide (NO) is a tiny gas molecule found throughout the circulatory system, causing relaxation of the cavernous smooth muscle of the penis as well as vasodilation (widening) of the penile blood vessels. These combined effects allow more blood to pass into the penis, causing a firmer erection.5,6

One of the biggest culprits for compromising NO levels, however, is inflammation – specifically inflammation of the endothelium (lining of the blood vessels).7 Vascular inflammation and the NO deficiency it causes are also to blame for other cardiovascular problems, like angina (chest pain), heart attacks, and strokes.

Erectile dysfunction can be a warning sign of other impending diseases

Even in “well-endowed” fellows, the vessels of the penis are relatively small compared to the arteries in other parts of the body. This makes the penile blood vessels fragile and sensitive to injury. The penis is therefore often the first place in the body to manifest the signs and symptoms of vascular disease.

If left untreated, the vascular inflammation and NO dysfunction associated with endothelial ED may begin to spread to blood vessels in other parts of the body, causing a variety of serious heart problems like angina (chest pain), heart attack, and stroke.8 Men can develop ED before they develop even so much as an elevated blood pressure reading!9 That’s why ED is sometimes referred to as “painless penile angina.”10

ED is a warning sign of poor vascular function and impending cardiovascular disease.

A shocking 70% of men with coronary artery disease (CAD) in one study reported that they had ED long before they developed any symptoms of CAD.11 ED is a warning sign of poor vascular function and impending cardiovascular disease.6,11-13

ED and CAD share many of the same risk factors, including obesity, sedentary lifestyle, smoking, high homocysteine levels, diabetes, high blood pressure, dyslipidemia (high cholesterol), and metabolic syndrome. All of these risk factors are also associated with poor NO activity.6,13-15

Won’t more testosterone help?

Testosterone plays an important role in sexual function via several mechanisms, including the stimulation of NO release,23 but it’s unlikely to control endothelial ED on its own for very long.

For some people with endothelial ED, testosterone replacement therapy (TRT) may help, but not sufficiently unless the dosage is ramped up high – too high. Guys on too much testosterone often experience irritability, anxiety attacks, insomnia, or other symptoms of testosterone overdose. Because of the hormone’s influence on red blood cell (RBC) production, furthermore, guys on TRT are at high risk of life-threatening events like blood clots, chest pain, heart attacks, and strokes. They’re also prone to acne, “backne” (pimples on the back), a reddish complexion, and/or a puffy appearance – effects that make a guy look a bit like the Kool-Aid Man.

For many fellows with endothelial ED, even high doses of testosterone won’t cause strong erections.

For many fellows with endothelial ED, however, even high doses of testosterone won’t cause strong erections, which does not mean that the man’s penis is “broken!”

If you have endothelial ED, it’s important to understand how and why your blood vessels are dysfunctional. Yes, there are of course nutritional supplements you can take to enhance nitric oxide production, but they’re unlikely to give you the best outcomes unless you’re also taking care to stop the cause(s) of your vascular inflammation. This is where diet and lifestyle become non-negotiable.

In the next post, we take a look at some healthy strategies for improving endothelial health, increasing nitric oxide levels, and achieving strong erections.

Improving Erectile Health – Part 2 of 2

Nitric oxide support for sexual health

In Part 1 of this series, we looked at the physiology of a type of erectile dysfunction (ED) known as endothelial ED and explained the importance of blood vessel health on male sexual function. This week, we will explore some natural strategies, that have good scientific evidence for improving vascular (and erectile) integrity.

Although not all men with ED have endothelial ED, many of them do. Nevertheless, just about everyone can likely benefit from these suggestions:

Eat vegetables – especially beets

Diets rich in vegetables have been shown to support overall heart health,[1],[2] lowering the risks of high blood pressure, heart attack, and stroke.[3],[4],[5] If you’re not eating vegetables – it’s never too late to start!

Make at least half of your plate at every meal greens (spinach, kale, chard, etc.) and/or brightly colored vegetables like purple cabbage, tomatoes, purple onions, carrots, and peppers. Beets (beetroot) are particularly effective in increasing nitric oxide (NO) levels, as they’re rich in nitrates, antioxidants, and phenolic compounds important for cardiovascular health.[6] Beets have been observed to increase NO levels and lower blood pressure readings in both men and women of various ages.[7],[8],[9]

Beets have been observed to increase NO levels and lower blood pressure readings in both men and women of various ages.

A powdered greens and/or powdered beetroot supplement (organic whenever possible!) can be a quick and easy way to consume more dietary nitrates.

Enjoy berries

Rich in flavonoids and antioxidants, blueberries, cherries, goji berries, and other berries are excellent for vascular health. Organic green tea, and dark chocolate can also fight oxidative stress, reverse endothelial dysfunction, and stave off cardiovascular diseases.[10]

Nix commercial mouthwash and stomach-reducing medicines

The brilliant human body converts the nutrients found in vegetables into NO. This conversion requires the presence of the right kind of bacteria in the mouth and enough stomach acid.[11]

Because most commercial mouthwashes kill both the good and the bad bacteria in the mouth, they may be contributing to endothelial ED and vascular diseases.

I also typically advise my clients to stay away from calcium carbonate tablets, omeprazole, and other medications that dampen stomach acid production.[12],[13],[14] (If you have acid reflux and think you need acid-reducing drugs, read this.)

L-arginine

The amino acid L-arginine is the raw material from which the body produces NO.[15] Low blood levels of L-arginine have unsurprisingly been correlated with poor NO production, and a significant percentage of ED patients have low levels of L-arginine and/or its precursor, L-citrulline.[16]

A significant percentage of ED patients have low levels of L-arginine and/or its precursor, L-citrulline.

L-arginine supplements may improve NO levels and erectile health – but with limited efficacy, as L-arginine only stays in the circulation for milliseconds at a time.[17] This may be why a review of L-arginine’s efficacy in the treatment of ED reports that a minimum dosage of 3 grams daily is necessary to achieve outcomes, and some studies have even dosed the amino acid at 5 grams.[18]

Thankfully, there is evidence that L-arginine may work significantly well when supplemented along with glutathione (GSH),[19] vitamin C,[20] pine bark extract,[21],[22] and/or L-arginine’s precursor, L-citrulline.

L-citrulline

L-citrulline is named for the watermelon, or Citrullus vulgaris, from which it is derived.[23] Unlike L-arginine, L-citrulline skips pre-systemic metabolism and effectively increases circulating NO levels.[24],[25] This might make L-citrulline a more advantageous nutritional supplement than L-arginine in the treatment of ED, hypertension, and related vascular conditions.[26],[27] It has also been shown to be an effective adjuvant to treatment with pharmaceutical PDE5 inhibitors (drugs like Sildenafil).[28]

What may be even more effective than L-arginine or L-citrulline monotherapy, however, is taking the two amino acids concurrently: Simultaneous oral supplementation of 1 gram of L-arginine and 1 gram of L-citrulline was shown to increase plasma L-arginine levels more than 2 g of either alone in a 2017 study.[29]

Caution: Because many viruses – including herpes simplex virus (HSV) – are dependent upon arginine for replication, L-arginine and L-citrulline supplements may be poorly tolerated by patients with frequent HSV outbreaks.[30]

French maritime pine bark extract

A standardized pine bark extract (SPBE) from the bark of the French maritime pine, Pinus pinaster – or Pycnogenol®, as it’s known in the U.S.A. by its patent name – has been shown to improve erectile function both as a standalone treatment and in combination with L-arginine.[31],[32]

SPBE has been observed to support the production and release of NO from the cells lining the blood vessels, improving forearm blood flow in humans in one study.[33]

SPBE has also been shown to improve erectile function, both as a standalone treatment and in combination with L-arginine.[34],[35] In one trial, for example, supplementation with SPBE (120 mg daily for three months) significantly reduced patients’ ED severity from moderate to mild.[36] The Pycnogenol group in this study was also observed to have increased plasma antioxidant activity and reduced total cholesterol and LDL-cholesterol levels as compared to the placebo group. These findings suggest that SPBE may not only treat ED, but also improve overall cardiovascular health.[37]

In another study of 40 males 25 to 45 years of age, a combination of L-arginine and Pycnogenol significantly outperformed Pycnogenol alone, helping 80% of men (and, after another month of the study, 92.5% of men) achieve a normal erection – as compared to only 5% of men who benefitted from Pycnogenol alone. Pycnogenol was given at a dose of 40 mg one to three times daily, with L-arginine at a dose of 1.7 g daily.[38]

A combination of L-arginine and Pycnogenol significantly outperformed Pycnogenol alone, helping 80% to 92.5% of men achieve a normal erection.

In a similar trial of 50 males, L-arginine (3 g per day) plus pycnogenol (80 mg per day day) restored normal erectile function after just one month of supplementation. Sperm quality improved in the men who took this combination and their testosterone levels increased significantly, thus suggesting enhanced fertility. The men also reported a doubling in their sexual intercourse frequency.[39]

Glutathione and other antioxidants

As the master antioxidant of the body, glutathione (GSH) strongly protects against the oxidative stress associated with endothelial dysfunction. GSH and other antioxidants may thus prevent oxidative stress, ameliorate vascular endothelial dysfunction, and stave off cardiovascular disease (among other chronic ailments).[40]

Supplementation with L-citrulline and GSH has also been shown to synergistically increase NO levels.[41]

DHEA

The steroid hormone precursor dehydroepiandrosterone (DHEA) enhances sex hormone production and positively effects NO levels, thus supporting endothelial health.[42]

A systematic review of 38 trials found that DHEA improves various aspects of sexual health.

A systematic review of 38 trials found that DHEA improves various aspects of sexual health in both males and females, including sexual interest, sexual frequency, lubrication, arousal, pain, and orgasm.[43] DHEA can also help with brain health.[44]

Avoid refined sugars and refined carbohydrates

Foods like breads, pastas, commercial pastries, candy bars, so-called “sports” drinks, sodas, most juices, cereals, crackers, and potato chips all increase blood glucose (sugar) levels and drive inflammation in the blood vessels. It’s no coincidence that men with diabetes and pre-diabetes are more likely to have ED than other guys.[45],[46]

Quit smoking and drinking

You know that smoking and drinking alcohol are harmful for your health, as does everybody else under the sun! These habits also create very high levels of inflammation and oxidative stress in the body, thus wreaking havoc on the circulatory system.[47],[48] ED may be a sign that it’s time to make some healthy lifestyle changes.

Mindfulness practice

NO helps with more than just the dilation of blood vessels: it also supports immune function, balances the nervous system,[49] and protects against various types of dementia.[50] NO helps us feel more relaxed, in turn supporting further NO production.[51] In fact, experienced meditators were found to have higher levels of NO precursors in their blood than non-meditators, in one study.[52]

Move your body

A sedentary lifestyle is a significant risk factor for ED and other cardiovascular diseases. Exercise is the number one lifestyle factor most strongly correlated with erectile health.[53]

Exercise is the number one lifestyle factor most strongly correlated with erectile health.

A review of ten studies found that moderate to vigorous aerobic exercise (four times weekly for six months) improved erectile function in men with ED caused by sedentary lifestyle, obesity, high blood pressure, cardiovascular disease, and/or metabolic syndrome.[54]

Physical activity is an effective way to prevent – and likely treat – ED because it increases NO levels, improves vascular function,[55] and increases testosterone.[56] Considering that exercise helps with a wide array of other health conditions, physical activity should be a part of just about every person’s day. (Too busy to move? Read our tips for fitting exercise into your day.)

Conclusion

During male sexual arousal, nitric oxide (NO) delivers blood to the penis, resulting in erection. Erectile dysfunction may therefore sometimes be a symptom of poor circulatory health, high vascular inflammation, and/or low nitric oxide (NO) levels – all of which can predispose a man to more serious problems like high blood pressure, angina, heart attack, and stroke. ED can therefore serve as an important warning signal of bigger problems to come.

Thankfully, some simple, natural strategies can make all the difference.

Note: The words “man,” “guy,” “fellow,” and “male” as used within this article refer specifically to individuals who were born with XY chromosomes and a penis. I acknowledge and honor that not all men are born with this anatomy, and that not all people born male identify with that gender.

Erectile Dysfunction: The Canary in the Cardiovascular Coal Mine?

Erectile Dysfunction: The Canary in the Cardiovascular Coal Mine?

The role of endothelial function on tumescence – and beyond


By Erica Zelfand, ND

The stories I hear of men* with erectile dysfunction (ED) are strikingly similar: The issue begins insidiously and is initially treated at a “low T clinic” with gradually increasing doses of exogenous testosterone in regimens that yield varied but ultimately insufficient results.

A review of the lab work of these individuals reveals that they are typically overdosed on their prescription hormones, with total testosterone levels often above 1000 ng/dL. While supraphysiological levels of testosterone do, in fact, enhance the sexual desire and performance of some men, they come with significant health risks and pesky side effects like anxiety, irritability, and insomnia. Other men, however, find that even high doses of anabolic steroids fail to engender desired outcomes in the bedroom.

Erectile dysfunction (ED, impotence) is a fairly common medical condition, characterized by the inability to achieve and maintain a penile erection firm enough for satisfying sexual intercourse.1 ED is also on the rise: While the condition affected an estimated 152 million males worldwide in 1995, that number is expected to swell (no pun intended) to over 320 million people by 2025.2,3

Just last week, a new patient shouted at his wit’s end, “I’m taking testosterone, HCG [human chorionic gonadotropin], and anastrozole. I’m lifting more weight than the other guys at the gym. I look amazing. I have tons of energy—so much I can’t fall asleep at night – but I after two years of playing with all my doses I still can’t get hard. What the heck is wrong with me!? What are my other doctors missing? I really hope you can figure it out.” [Note: This patient employed more expletives when expressing himself.]

Time and time again, I explain to exasperated fellows like this one that sex hormone levels are just one piece of the puzzle. The successful treatment of ED often also entails assessing the nervous system (including mental health), adrenal function, metabolic health, and endothelial integrity, with the latter being among the most overlooked aspects of sexual health.

Tumescence is a hemodynamic process characterized by enhanced penile arterial inflow and reduced venous outflow.4,5 Because the physiology of tumescence (penile erection) requires that the penis engorges with blood, the integrity of the vascular system—and ergo the status of nitric oxide production—is of utmost importance to male sexual performance and satisfaction.6


Nitric Oxide: The Endothelium Relaxer

Our understanding of nitric oxide (NO) is relatively new: In 1998 three American pharmacologists received the Nobel Prize for their discovery of NO’s effects as a signaling molecule within the cardiovascular system.7

This tiny gas molecule is produced in the blood vessels, nerves, and immune cells. Neuronal and endothelial NO causes relaxation of the surrounding smooth muscle, resulting in vasodilation.8,9 With regard to male sexual health, NO triggers the relaxation of the cavernous smooth muscle of the penis, allowing for engorgement and  subsequent erection.

NO production declines with age, however, placing males at increased risk of ED as they grow older.10 It is now estimated that nearly half of men above the age of 40 have some degree of ED.11

Endothelial inflammation undermines NO production and is thus a significant determinant of ED and other vascular diseases.12 It is also a culprit that can effectively be treated with naturopathic medicine.


Erectile Dysfunction as Coronary Risk Marker

Due to the relatively small size of the penile vasculature (on even the most well-endowed of individuals), ED may be understood as a warning sign of poor vascular function and impending coronary artery disease (CAD).9,11,13,14 ED may present well before the observation of so much as an elevated blood pressure reading.15 If left unchecked, the vascular inflammation and dysfunction associated with many cases of ED may lead to ischemic heart disease;16 ED has thus been referred to as “penile angina.”17

ED is such a strong predictor of cardiovascular disease in men,3 in fact, that providers are now advised to assess the cardiovascular health of patients presenting with the condition.16 While not all men with ED have cardiovascular problems, a significant percentage of males with angiographically demonstrated CAD have been observed to have ED.13 ED was also shown in one study to precede CAD in a whopping 70% of male CAD patients.13

It is perhaps no surprise that ED and CAD go hand-in-hand, as they share many of the same risk factors, including sedentary lifestyle, obesity, diabetes, smoking, hypertension, dyslipidemia, metabolic syndrome, and declining NO activity.9,11,18,19

Conventional Treatments of ED

The first-line therapy for ED entails phosphodiesterase type 5 inhibitors (PDE5i) like sildenafil.20 Although these drugs do not directly increase NO, they do augment NO-mediated pathways.21

When PDE5i’s fail to improve symptoms, vacuum devices, intracavernous injections, and penile prosthesis implantation are considered second- and third-line therapies. Few patients are eager to try these interventions, however, which may not be too great of a tragedy, as none of these methods adequately addresses the underlying metabolic, neurological, hormonal, or endothelial aspects of ED.

Testosterone plays an important role in sexual function via several mechanisms, including the stimulation of NO release.22 As more and more males become afflicted with ED, the increasing number of “low T” clinics that have cropped up over the years now comprise a multi-billion-dollar industry.23,24 Testosterone replacement therapy (TRT) does help many men with ED—though not all. In my experience and opinion, focusing on NO augmentation—either in lieu of or in addition to hormone prescription—may serve ED patients in both the short and long term.

Erectile Dysfunction: The Canary in the Cardiovascular Coal Mine?

Two Pathways of Nitric Oxide Production

There are two pathways by which NO is created in the body (see Figure 1).25 One pathway entails the reduction of dietary nitrates to nitrite and then NO.26 Another pathway depends upon the enzyme nitric oxide synthase (NOS) to convert L-arginine to NO.27

Oral Hygiene

In the NOS independent pathway of NO production, facultative oral microflora reduce dietary nitrates (NO3) to nitrites (NO2), which are then converted to NO in the acidic environment of the stomach.26

In this pathway, the presence of particular oral bacteria and the stomach’s low pH are invaluable for NO production. These requisite conditions are undermined, however, by antiseptic mouthwashes, proton-pump inhibitors, and over-the-counter antacid medications—agents commonly used in industrialized societies.28–30 Although restoring a patient’s gastric acidity is a relatively straightforward task for the naturopathic physician, as of this writing there is no nutritional probiotic supplement that contains the oral bacteria essential for nitrate reduction. We may still, however, advise patients to avoid commercial mouthwash products.26


Dark Leafy Greens and Beetroot

Vegetable-rich diets have been shown to support heart health,31,32 in part due to their nitrite and nitrate content. High nitrate diets lower the risks of hypertension, heart attack, and stroke,33–35

Although dietary nitrites such as those naturally found in bacon have been vilified, nitrites and nitrates are actually naturally occurring molecules produced in the body that are important to health.36,37 (The culprit in processed meats is likely not nitrite, but rather the carcinogenic compound nitrosamine.38,39)

In addition to eating plenty of green, leafy vegetables, powdered greens products, beetroot (also known simply as “beets”), and beetroot products may all be used as supplemental sources of nitrates, antioxidants, and phenolic compounds pertinent to cardiovascular health.40 Beetroot is a particularly rich source of nitrates and antioxidant compounds and has been observed to increase NO levels and lower blood pressure readings in both men and women of various ages.41–43

Although dietary nitrites such as those naturally found in bacon have been vilified, nitrites and nitrates are actually naturally occurring molecules produced in the body that are important to health.36,37 (The culprit in processed meats is likely not nitrite, but rather the carcinogenic compound nitrosamine.38,39)

In addition to eating plenty of green, leafy vegetables, powdered greens products, beetroot (also known simply as “beets”), and beetroot products may all be used as supplemental sources of nitrates, antioxidants, and phenolic compounds pertinent to cardiovascular health.40 Beetroot is a particularly rich source of nitrates and antioxidant compounds and has been observed to increase NO levels and lower blood pressure readings in both men and women of various ages.41–43

L-Arginine and L-Citrulline

L-Arginine may be acquired from nutritional supplements and/or endogenously derived from the amino acid L-citrulline, and serves as the source raw material from which the body produces NO via NOS (Figure 1).44 Low serum levels of L-arginine have unsurprisingly been correlated with poor NO production.45

A significant percentage of ED patients have low L-arginine or L-citrulline levels, placing them at increased risk of disease.45 Because of this and because the NOS-dependent route of NO production was the first pathway discovered, the nutraceutical product market is now replete with L-arginine-containing formulae.46

Although oral L-arginine supplementation may improve NO-mediated vasodilation and endothelial function, its effects as a monotherapy are transient due to the short duration of its presence in the circulation (on the order of milliseconds).47 This may be why a review of L-arginines efficacy in the treatment of ED reports that a minimum dosage of 3 g daily is necessary to achieve outcomes. Some studies have even dosed the amino acid at 5 g and higher.48

The efficacy of L-arginine may be improved by delivering it alongside N-acetylcysteine or glutathione (GSH), both of which contain sulfur residues or thiols. NO binds GSH, forming S-nitrosoglutathione. This molecule then transports and circulates NO, has a half-life of hours, and is just as vasoactive as NO.49 Antioxidants like ascorbate also are able to cleave or release bound NO.50 L-arginine also pairs particularly well with Pycnogenol, as is explored in the section below.

Unlike L-arginine, its precursor L-citrulline (named for the watermelon, or Citrullus vulgaris, from which it is derived51) evades presystemic metabolism, effectively increasing circulating NO levels.45,52,53 This may make L-citrulline a more advantageous nutritional supplement than L-arginine in the treatment of ED, hypertension, and related vascular conditions.54,55

Although L-citrulline supplements are less effective than PDE5i’s (at least in the short term), they are an effective adjuvant to PDE5i treatment.54,56 L-citrulline has also been shown to be safe and psychologically well tolerated.54

What may be even more effective than L-arginine or L-citrulline monotherapy, however, is the administration of the two NOS substrates concurrently: Simultaneous oral supplementation of L-arginine and L-citrulline (1 gram of each) increased plasma L-arginine levels more than 2 g of either alone in a 2017 study.57 (Note that because many viruses, including herpes simplex virus [HSV], are dependent upon the bioavailability of arginine,58 L-arginine and L-citrulline supplements may be poorly tolerated by patients with frequent HSV outbreaks.)

In addition to augmenting the body’s supply of L-arginine, it is also important to support conversion of the amino acid into NO.38 This conversion is enhanced by oxygen, NADPH, heme, tetrahydrobiopterin (THB, also known as BH4), and other coenzymes. Things as simple as checking oxygen saturation and ferritin levels may therefore prove advantageous.


Pycnogenol

A standardized extract from the bark of the French maritime pine, Pinus pinaster—or Pycnogenol, as it’s known in the US by its patent name—can improve erectile function both as a stand-alone treatment and in combination with L-arginine.59,60

In a double-blind study of 21 males suffering from ED, patients received 120 mg of Pycnogenol or placebo daily. After three months, Pycnogenol significantly improved the symptoms of ED from moderate to mild stage. Perhaps more importantly, a significant increase in plasma antioxidant activity was noted among those who received Pycnogenol, while no such benefit was found in those who received placebo. The Pycnogenol group further enjoyed reductions in total cholesterol and LDL-cholesterol levels (from 5.41 to 4.98 mmol/L and from 3.44 to 2.78 mmol/L, respectively). (No significant changes in triglycerides or HDL were observed.) These findings suggest that Pycnogenol may not only treat ED but may also temper some of the more serious vascular changes that succeed it.61

In another study of 40 males, 25 to 45 years of age, a combination of L-arginine and Pycnogenol significantly outperformed Pycnogenol alone, helping 80% of men (and, after another month of the study, 92.5% of men) achieve a normal erection – as compared to only 5% of men who benefitted from Pycnogenol alone. Pycnogenol was given at a dose of 40 mg one to three times daily, with L-arginine at a dose of 1.7 g daily.60 (It is worth noting that the minimum effective daily dosage of L-arginine as a standalone treatment of ED may be 3 g,62 though this study suggests that lower doses may be used within the milieu of co-treatment with Pycnogeol.)

In a similar trial of 50 males, L-arginine (3 g/day) plus Pycnogenol (80 mg/day) restored normal erectile function after just one month of supplementation. Sperm quality improved in the men who took this combination and their testosterone levels increased significantly. The men also reported a doubling in their sexual intercourse frequency.63


Glutathione and Other Antioxidants

Supplementation with L-citrulline and GSH has also been shown to synergistically increase NO levels.

In addition to providing thiols for the formation of S-nitroso glutathione, GSH also affects the NOS enzyme function. In a GSH-depleted environment, NOS becomes uncoupled, resulting in the production of toxic superoxides instead of salubrious NO. Endothelial NOS (eNOS) uncoupling has been implicated in numerous conditions marked by vascular endothelial dysfunction, including heart failure, ischemia/reperfusion injury, hypertension, atherosclerosis, and diabetes.65

As the master antioxidant of the body, GSH strongly protects against the oxidative stress associated with endothelial dysfunction. Like other antioxidants, GSH may prevent eNOS uncoupling by scavenging free radicals, mitigating certain radical-generating pathways, maintaining the optimal ratio of reduced to oxidized glutathione, and protecting the endothelium against damage by toxic metabolites.66

GSH and other antioxidants can thus prevent oxidative stress, ameliorate vascular endothelial dysfunction, and stave off cardiovascular disease (among other chronic ailments).66


DHEA

The steroid hormone precursor dehydroepiandrosterone (DHEA) not only augments hormone production, but also positively affects eNOS. Supplementation with DHEA may thus further support endothelial health.67 A systematic review of 38 trials found that DHEA improves various aspects of sexual health in both males and females, including sexual interest, sexual frequency, lubrication, arousal, pain, and orgasm.68


Carnitine and Taurine

Carnitine and taurine have been shown to support NO production and vascular health. Specifically, propionyl-L-carnitine (PLC) has been observed to stimulate NO production and facilitate the delivery of free fatty acids into the mitochondria.69 When administered alongside acetyl-L-carnitine, PLC enhances the efficacy of sildenafil in treating the symptoms of ED in men who have undergone bilateral nerve-sparing prostatectomy.70

Taurine also increases NO, likely by decreasing asymmetric dimethylarginine (ADMA), as an inhibitor of NO synthesis.71,72

Meditation

Beyond erectile function and blood pressure, NO’s benefits include blood clot prevention, immune function enhancement, and nervous system support.7 NO may also contribute to the relaxing effects of meditation and mindfulness practice—and mindfulness practice may likewise enhance NO production.73 In one study, for example, experienced meditators were found to have lower levels of subjective stress and higher nitrate and nitrite levels.9 This finding may be added to the long list of reasons to recommend meditation and other mindfulness-based practices to those with ED and other cardiovascular ailments.


Exercise

Sedentary lifestyle is a significant risk factor for both ED and cardiovascular disease.9 Physical activity is known to increase vascular NO levels and improve vascular function,74 which explains at least in part why exercise is hailed as the lifestyle factor most strongly correlated with erectile health.74,75

A 2018 systematic review of 10 studies concludes that moderate to vigorous aerobic exercise four times weekly for six months improves erectile function in men who have ED caused by sedentary lifestyle, obesity, hypertension, cardiovascular disease, and/or metabolic syndrome.9 Considering that exercise helps with a wide array of other health conditions, physical activity should be a basic treatment guideline for just about every patient.


Conclusion

During sexual arousal, the vessels of the penis rely upon nitric oxide to help blood—and the oxygen and nutrients it carries—engorge the penis, resulting in tumescence. Erectile dysfunction may therefore represent poor endothelial health and a deficit of NO in many cases—and thus serve as a warning sign of more serious vascular ailments to come.

Because there is no standard lab test for assessing NO levels,76 it is important for healthcare providers to make astute clinical assessments of their patients’ cardiovascular status when labs and imaging fall short.

Simple, natural strategies and supplements—like oral health, digestive hygiene, green vegetables and beetroot, L-arginine, L-citrulline, glutathione, DHEA, carnitine, Pycnogenol, meditation, and exercise—may well serve the men who suffer from erectile dysfunction. Even in the context of testosterone replacement and phosphodiesterase inhibitor prescription, nitric oxide support may further improve sexual performance and safeguard against more serious vascular disease.

  • L-Arginine and L-Citrulline
  • Pycnogenol
  • Glutathione and Other Antioxidants
  • Carnitine and Taurine
  • __Berkeley Life Pro, __ M3 Powder, __  NO Max ER
  • Testosterone __ IM, __Troche,__ Topical
  • DHEA
  • Meditation
  • Exercise