Take Arginine or Not? Lessons from the *Arginine Paradox.* Taking arginine blocks nitric oxide production. What's the problem?

The Arginine Paradox

Taking Arginine is Useless or Dangerous

Boost Nitric Oxide Levels With Arginine, Right? Wrong!

Unfortunately aging and stress cause our bodies to produce less nitric oxide. In fact, researchers have found that aging and stress reduce our ability to produce nitric oxide through the L-arginine pathway. So, when you need nitric oxide the most, you're most likely to be deficient. (448)

Aging and stress reduce our ability to produce
nitric oxide from L-arginine.

So, the common advice is to take L-arginine supplements. But, in fact, the vast majority of people are not deficient in arginine and so taking an arginine supplement is ineffective or actually detrimental. (401,453,485)

Recent medical research shows L-arginine treatment worsens microvascular circulation (endothelial function) and executive cognitive function in older persons with cardiovascular risk factors.
Journal of the American Society of Hypertension, 2018 (485).

When endothelial dysfunctions, the endothelial cells produce superoxide instead of nitric oxide. Blood flow decreases, muscles surrounding vessels constrict, platelets activate (sticky)

(Above:) Oxidative stress causes endothelial dysfunction where endothelial cells create superoxide—rather than nitric oxide. (439)

It's true that your body produces arginine in order to make nitric oxide. But it's also true that supplementing with arginine may actually block nitric oxide production. Researchers call this the "Arginine Paradox." What's the problem with taking L-arginine supplements? (401,433,447)

"Arginine metabolism is very complex...

Nitric oxide production depends mostly on the efficient recycling of arginine-derived citrulline back to arginine, and not so much on exogenous [outside of the body] arginine supply." (401)

The Arginine Paradox

Scientists have discovered "the more arginine is introduced, the more it is destroyed, eventually leading to impaired nitric oxide production." (401)

"An even more puzzling paradox is that long-term arginine supplementation is ineffective in improving eNOS [endothelial nitric oxide synthesis] activity." The researchers then warned, "Even worse, exogenous [supplementation with] arginine increased mortality [death] when arginine was given to promote vasodilation in patients after a myocardial infarction [heart attack]." The largest controlled clinical study on oral arginine supplementation in heart-attack survivors was terminated early because of "excess mortality." (401,450,451,452)

"In summary, oral arginine supplementation not only increases arginine disposal through [urine] but also promotes insulin resistance." The researchers conclusion was that "arginine supplementation should be avoided, because it does not resolve the reasons underlying its excess consumption or blunted synthesis, and, on the contrary, may actually worsen them. The usual paradigm of clinical nutrition, assuming that what is lacking should be provided, may here prove to be wrong." (401)

Taking L-arginine may contribute to nitric oxide toxicity and worsen inflammation.

Researchers discovered that taking arginine when you have inflammation creates more inflammation and fails to improve nitric oxide levels. (447)

"There is mounting concern that arginine supplementation during an inflammatory state could be detrimental due to overwhelming nitric oxide production. A key finding of this study is that arginine supplementation did not increase serum nitric oxide levels over that observed in elders with [inflammation]." (447)

Nitric oxide is essential in fighting infection, killing tumor cells and promoting wound-healing. As long as nitric oxide is produced in the right amount, it's beneficial to the body. But when nitric oxide is produced in excess, it causes some of the body's worst free-radical damage. (14,232-236)

Too much nitric oxide contributes to heart disease and strokes, arthritis, asthma and Alzheimer's disease. (10,239,265,292,296)

How to Improve Nitric Oxide Levels

Flavay® Elevates Nitric Oxide Synthesis to Normal Levels

Improve Endothelial Dysfunction

Flavay® elevates nitric oxide synthesis and antioxidant levels to normal by improving endothelial dysfunction. Both in vivo and clinical studies show Flavay® balances nitric oxide activity, both to stimulate normal synthesis and inhibit over-production of nitric oxide. Flavay® protects against toxic overproduction of nitric oxide by blocking nitric oxide synthases. (10,53,261,265,302,306,315,372,414)

Flavay® is shown to improve vasodilation and mildly inhibit angiotensin-converting enzyme (ACE) by modulating nitric oxide metabolism in endothelial cells. (292,296,358)

Also, endothelial nitric oxide acts to increase the production of a chemical messenger called "cyclic-GMP" (guanosine monophosphate), which is needed to keep blood platelets relaxed and not prone to clumping or aggregation. (239,265,286,287,292,296)

Elevate Antioxidants to Normal Levels

Research also shows taking Flavay® specifically increases vitamin E (a-tocopherol) antioxidant levels in endothelial cells. (292)

A study comparing activity and synthesis of superoxide dismutase (SOD) and nitric oxide levels in diabetic and non-diabetic cerebellum and cerebral cortex shows diabetes significantly decreases synthesis and activity of SOD and Flavay® significantly increases synthesis of SOD. Also, diabetes reduces synthesis of nitric oxide but Flavay® elevates nitric oxide levels back to normal. (372)

Taking Flavay® as much as doubles plasma antioxidant levels and activities of vitamins C and E and A, and catalase, superoxide dismutase (SOD) and glutathione (GPx). (33,64,64,71,361,371)

For good cardiovascular and brain health, our body needs to maintain the right balance of nitric oxide—and that's what Flavay® effectively does. (10,239,265,292,296)

Flavay improves endothelial function and nitric oxide levels in endothelial cells and platelets. Blood flow increases, muscles surrounding vessels relax (vessel dilate), platelets relax (unsticky)

(Above:) Studies show when Flavay® improves endothelial function, nitric oxide levels are restored so blood flow increases, and muscles surrounding vessels relax. (239,265,286,287,292,296)

Both human and scientific studies show Flavay® induces vasorelaxation and vasodilation by nitric oxide formation in endothelial cells by endothelial nitric oxide synthase (eNOS). (53,265,261,302,314,343,344,361,362,418,419,420)

Studies show Flavay® improves vasodilation and mildly inhibits angiotensin-converting enzyme (ACE) by modulating nitric oxide metabolism in endothelial cells. (292,296)

Studies show Flavay® maintains optimal nitric oxide levels, it both stimulates normal synthesis of nitric oxide and inhibits overproduction of nitric oxide. Flavay® significantly suppresses inducible nitric oxide synthase (iNOS) gene expression and NO production in endothelial cells, thereby directly protecting vascular walls against damage. (53,265,302,343,344,361,362,414)

Study shows Flavay® improves endothelial progenitor cells viability and function, while preventing endothelial dysfunction. (421)

Flavay® possesses endothelium-dependent-relaxing (EDR) activity in blood vessels by increasing nitric oxide production and stimulates vascular endothelial growth factor, a signaling factor involved in initiation of wound healing. (53,265,274)

Flavay® promotes nitric oxide production by vascular endothelium, inhibits the synthesis of thromboxane in platelets and leukotriene in neutrophils, modulates the synthesis and secretion of lipoproteins, arrests tumor growth, and inhibits carcinogenesis in different models. (10,265,302,306)

Nitric oxide stimulates collagen synthesis and subsequent healing at wound sites. (312,313)

In addition, the induction of vascular endothelial growth factor (VEGF) is a crucial step in the reepithelialization phase of skin repair. (314,315)

Flavay® is shown to stimulate the expression of VEGF in cultured keratinocytes, showing Flavay® supports wound healing. (316,317)

Experiments show Flavay® relaxes sympathomimetic-induced contractions in a concentration-dependent manner. Flavay® also increases nitric oxide (NO) levels, counteracting the vasoconstrictor effects of sympathomimetics. (10,265)

In endothelial cells challenged with reactive nitrogen species, Flavay® protected against vitamin E depletion, potentially protecting vascular endothelium from oxidative stress from reactive nitrogen species such as nitric oxide. (261,301)

Study comparing activity and synthesis of superoxide dismutase (Cu/Zu-SOD) and nitric oxide in the diabetic and non-diabetic cerebellum and cerebral cortex shows: Diabetes significantly decreases synthesis and activity of Cu/Zu-SOD and Flavay® significantly increases synthesis of Cu/Zu-SOD. Diabetes reduces synthesis of nitric oxide and Flavay® elevates levels back to normal. (372)

Study shows daily supplementation of Flavay® improves vascular endothelial dysfunction associated to diabetes mellitus. Flavay® is shown to significantly improve vasodilation and to preserve norepinephrine-induced contractions. (424)

Studies show Flavay® improves endothelial dysfunction, nitric oxide synthesis and antioxidant levels. (10,53,261,265,302,306,315,372,414)

Your blood flows better and your joints hurt less with Flavay®.

My joints aren't hurting and my back feels better and I'm even able to work better. I'll tell you, I can feel Flavay! —Ms. C.V.*

I have lupus and taking Flavay enables me to move. I'm not able to do without it. I've been taking it for more than a decade and my skin looks younger, in fact people think I'm my kid's sister. —Ms. L.B.*

After about 6 to 9 weeks it made a profound difference. I’ve lost inches in swelling. I cannot say enough about Flavay! Over the years, I’ve stopped and started again and found for vascular and lymphatic edema, nothing is better than Flavay. —Ms. Marie D.*

I just want to say that I love Flavay. When I stop taking it, the pain comes right back. —Mr. Mark H.*

I feel flexibility, while tying my shoes, wow! The simple things work better. I feel a general sense of wellbeing with Flavay. —Mr. Peter M.*

I love your product called Flavay. I feel it does the job! —Mr. Robert B.*

I've got to have my Flavay. Keeps me going. Keeps me young. 4 Flavay every day. —Mr. C.S.*

I had a terrible accident where I fell 20 feet and injured my back and it was really bad. I went from a wheelchair to a cane and now I'm mowing the lawn. Flavay shrank the protruding disk so I could stand up straight again. I've referred many many people to your products, and it worked for them too. —Mr. Dave T.*

Flavay is a product I cannot stop taking. When I stopped taking it for a couple of weeks, my neuropathy and arthritis pain come raging back. So I started again on Flavay and the pain is almost completely gone. —Ms. Elsa D.*

I started taking Flavay for arthritis pain and I feel so much better! I'm so thrilled! —Ms. Susan S.*

After taking Flavay for just a week, my sister is doing things she couldn’t do before, such as bending over to pick things up off the floor. —Mr. Joe C.*

The puffiness in my legs is so much better. Oh my gosh this Flavay is great! —Ms. Joan G.*

Your Flavay really helps my husband's chronic pain syndrome and we're almost out! Please ship asap! —Ms. S.W.*

I was taking Flavay for pain and mobility. Now I take Flavay as much for the benefits to my skin as for joint pain. —Mr. H.S.*

Oh, I just love Flavay! I feel so much better! —Ms. Y.L.*

I can’t even tell you how much I appreciated finding your product Flavay and the incredible results and relief I have gotten from taking it... I skeptically ordered two bottles... And low and behold, it works. I read that I could take more than 2 that some people had to take 4 or 5 at a time, so I did, hoping and praying, and my prayers were answered. To say thank-you is an understatement, and I have been able to stop all other pain meds. I honestly was on a one way road to nowhere, now I am free again..a feeling I haven’t had in over 12 years. Thank-you!!!!!!!!!!!!!!! —Ms. Beth B.*

I am a nutritionist and I have referred two of my clients to take Flavay. Both of my clients have raved about the product. One of my clients has a problem with circulation and she said Flavay really works for her. —Mr. John H.*

I've got to have my Flavay. Keeps me going. Keeps me young. 4 Flavay every day. —Mr. C.S.*

My neighbor is so pleased with Flavay telling me how much better she feels. She has heart problems and taking 2 Flavay per day she has so much energy again and her color is better too. —Ms. C.V.*

I have tried everything else and your Flavay really helps my eyesight. I was having trouble seeing at night and now I don't have that problem anymore. I love Flavay. I also had a blown knee that they had wanted to do surgery on and now I don't have to. I love the Flavay, I really like it! —Ms. T.K.*

I start feeling pain in my joints after a few days of not taking Flavay. —Mr. Mark H.*

My daughter has rheumatoid arthritis in her knees and years ago Flavay had really helped her, so I want to order some more for her. —Ms. K.M.*

For several years I took Flavay for fibromyalgia and it really worked and I felt so much better. Now I need to start again. —Ms. C.H.*

I love your product called Flavay. I feel it does the job! —Mr. R.H.*

I have had joint pain in my hips for a couple years. I have been taking Flavay for about 30 days and I realized I don't have hip joint pain when laying down or sitting for long periods! I will continue to take it daily. —Ms. M.H.*

Thank you so much. I'm desperate!! 😊 Haven't taken them (Flavay and Flavay Plus) for a few months and can tell the difference! —Ms. S.A.*

Since I started taking Flavay I felt so good and I'm hoping to keep getting better. I started taking Flavay for my knee but since I started taking Flavay I've cut way back on asthma meds. The medication affects my brain badly. I want to control asthma instead of it controlling me. Flavay is a big help, I am so happy! —Ms. J.I.*

I began giving my daughter Flavay Plus for ADD and then I decided to add Flavay for my daughter's allergies. I want to tell you, the Flavay works like a charm for my daughter’s allergies. She is 6 years old, and when we ran out of capsules this week she told me, “You've got to get more Flavay!” —Ms. S.S.*

I just wanted to write and say WOW... I was so skeptical of your product at first and really had a negative attitude when I started taking it. I am a 40 yr old female with anxiety, mild ADHD and a host of arthritis and inflammation issues. It was a struggle for me to get out of bed everyday and focus on what needed to be done. I had no focus, no attention span, no energy, and no desire to do anything. About a week into taking Flavay and Flavay Plus, I started noticing that I could think a little clearer. My rheumatoid arthritis flare-ups weren't so bad, though I still have them. feeling better, and having more energy. I never thought I would feel like my old self again. I don't know exactly how you do it,...but this stuff works! I am telling all of my friends to try it because you've given me my old life back! Thank you! —Ms. L.A.*

I am not one to review products, but i can't deny some of the benefits i've experienced using both your biomor curcumin and flavay products. I've been taking both for a few months now, and the two major benefits i've noticed are 1) joint strength and mobility (for workouts) as i am lifting much heavier weights without injury 2) I am a paroxsymal Afib sufferer, and my episodes have gone from 2-3 per week down to zero (most weeks). This can't just be a coincidence. I think there is definitely something in your formulas that stop inflammation and get your body in balance and healing itself. —Mr. B.V.W.*

I damaged both knees in a motor cycle accident, (mostly pain and swelling ). I don't even think about my knees anymore , its been that long since they have caused me any pain. I have been taking Flavay for 3 Years, I had my right wrist diogonsed with carpal tunnel syndrome, ( hand and arm going to sleep) after having surgery on the left arm years ago, did not have the time for surgery( 3 week recovery) but since Flavay no more pain , the pin and needles are gone so I don't wake up in the middle of the night with my arms and hands bothering me. The amazing thing about this product it can take care of problems you just forgot you had, (or just learned to live with) . Now forget about them because the pain is gone. —Mr. B. Hall*

I really notice a difference when taking Flavay Plus, both in inflammation and in my stress levels. —Ms. W.L.*

I'm real happy about Flavay. It seems to have a positive effect on my lymph system. —Ms. R.M.*

I just love Flavay. If you ever need do a commercial, I’ll be happy to do it! —Ms. Linda M.*