Dr. Geoffrey Nase Rosacea Treatment Blog | Rosadyn Treatment | Treat Facial Flushing and Redness

Rosacea-In-Focus: Nitric Oxide’s Effect on Rosacea, Redness, Flushing, Skin Inflammation and Progression

Nitric Oxide and Skin Blood Flow
Over the last few years, technological advancements in vascular research, drug development and transdermal delivery systems have brought new hope for rosacea sufferers. Rosacea has finally started to receive the attention and focus it deserves. Vascular specialists are now able to research and test treatments for blood vessel dysfunction, uncontrolled vascular growth and facial flushing, the three primary underlying causes of rosacea. The new objectives for rosacea research and treatment are to identify and suppress the mechanisms behind these vascular disturbances.  This, in turn, should cause regression of most rosacea symptoms. Furthermore, if the main mechanisms behind vascular dysfunction are suppressed, rosacea sufferers will no longer have the burden of avoiding all their flushing triggers.  Nitric oxide is one of the single most important targets for rosacea treatment as it is the main culprit behind all three rosacea disturbances.

Nitric oxide is a powerful dilator chemical that is produced by enzymes located in and around skin blood vessels.  Collectively, these enzymes are called nitric oxide synthase enzymes. Recent clinical studies demonstrate that nitric oxide is intimately involved in many inflammatory skin disorders including rosacea, psoriasis, atopic dermatitis, irritant dermatitis, and allergic dermatitis.

In the facial skin, nitric oxide is produced from:

• The inner wall of blood vessels

• Epidermal and dermal cells

• Dilator nerves around blood vessels

After nitric oxide is produced from these cells→it diffuses to nearby blood vessels and binds to receptors on vascular smooth muscle cells→ causing potent dilation and substantial increases in blood flow.  Topical medications that block nitric oxide production hold the potential to clear rosacea redness, skin inflammation and inhibit most forms of facial flushing. For many rosacea sufferers this would result in complete clearance of rosacea symptoms and remission.

Photo illustrations of nitric oxide-induced facial redness, flushing and skin inflammation: As one can see by the photos to the left, nitric oxide can cause significant redness and inflammation.  Overproduction of nitric oxide not only causes the characteristic redness seen in the ‘red nose’ photo, but it also triggers papule and pustule production in rosacea skin as depicted on the right-hand side photo.  Nitric oxide is not only a key factor in the development of rosacea symptoms and triggers, but this powerful dilator chemical triggers rosacea progression into the more severe stages.  Nitric oxide feeds the vicious inflammatory skin cycle by stimulating chronic dilation of blood vessels and subsequent inflammation – each of these processes brings inflammatory cells to the skin, interferes with the normal immune response and sensitizes skin cells, blood vessels and nerves.

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Nitric Oxide’s Role in Facial Flushing and Rosacea Progression
Most specialists in the rosacea field believe that nitric oxide plays an important role in facial flushing and rosacea progression.   Below are a few medical references on this important topic:

• In a superb medical article in the Archives of Dermatology (1996), Drs. Qureshi and colleagues, from Massachusetts General Hospital, USA, speculate that nitric oxide may be involved in the pathogenesis of facial redness, facial flushing, and rosacea.  They state, “Whatever the cause for erythema in the skin, whether excessive sun exposure or an inflammatory process, the final mediator may be nitric oxide.  Inhibitors of nitric oxide production may thus provide a valuable mode of therapy to relieve symptoms of flushing and erythema in the skin.” These medical experts also pose the ultimate question, “Could the erythema that is so difficult to treat in patients with rosacea be reversed with nitric oxide synthase inhibitors?”

• In the medical article, “Nitric Oxide and its Implications in Skin Homeostasis and Disease: A Review”, Drs. Bruch-Gerharz and colleagues discuss the therapeutic actions of topical nitric oxide inhibitors.    They suggest that rosacea may be one of the most important targets for nitric oxide inhibitor therapy. They further state that topical nitric oxide inhibitors may be available in the near future.

• In a recent clinical study in the Journal of Investigative Dermatology (1997), titled, “Influence of NO-Synthase Antagonists in Rosacea Patients”, Dr. Sauermann and colleagues detailed their findings on the effect of topical nitric oxide inhibitor therapy on rosacea patients. They found that treatment with a topical nitric oxide inhibitor (1% L-NAME cream, 2 times daily for 3 weeks), resulted in significant improvement of vascular symptoms in all rosacea patients.  These findings are very exciting, indicating the great potential for topical nitric oxide inhibitors in the treatment of rosacea.

Nitric Oxide’s Role in Inflammatory Skin Disorders
Numerous clinical studies demonstrate that nitric oxide also plays an important role in other inflammatory skin disorders. These studies indicate that nitric oxide is one of the key mediators of skin flushing, redness and inflammation no matter what the trigger.   Below are two studies highlighting this fact:

• In a recent medical article in the Journal of Investigative Dermatology (1999), Drs. Ormerod and colleagues demonstrated that nitric oxide can cause significant flushing and inflammation in human skin. They suggest that their results are consistent with other studies demonstrating that increased nitric oxide production is involved in psoriasis, atopic dermatitis, irritant dermatitis, allergic dermatitis, lupus erythematous, sunburn-induced flushing, nerve-mediated flushing, and skin swelling. They conclude that topical nitric oxide inhibitors may be of therapeutic use in many forms of skin inflammation.

• In a controlled clinical study in the International Journal of Dermatology (1995), titled, “Clinical Application of Nitric Oxide Synthase Inhibitor for Atopic Dermatitis”, Dr. Morita and colleagues detailed their preliminary findings on the effect of a topical nitric oxide inhibitor on 15 patients with an inflammatory skin disorder. They found that treatment with a topical nitric oxide inhibitor (1% NLA cream, 2 times daily for 4 weeks), resulted in significant improvement in skin redness in 66% of the cases, and reduced uncomfortable skin sensations in 80% of the patients.  No side effects were noted in any patients.

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Nitric Oxide’s Role in Skin Flushing
Nitric oxide is intimately involved in many forms of skin flushing because it is produced in great concentrations from the inner wall of skin blood vessels.  Nitric oxide is produced continuously to ensure adequate blood flow to the skin, and can be generated in response to a wide variety of stimuli such as chronic skin inflammation, blood vessel damage, increased blood flow conditions, external warming of the skin, environmental insults, internal body overheating, exercise, skin irritation, sunlight, nerve activation, hormones, stress, and in response to dozens of normally produced substances within the body. These findings strongly suggest that even though rosacea sufferers may have different underlying triggers for facial redness, flushing, and rosacea progression, nitric oxide may be one of the key final mediators in causing the vascular response. Below are some important findings on this subject.

1.   Nitric oxide is continuously produced from the inner wall of blood vessels in the skin: During resting conditions, the inside of the blood vessel wall continuously produces low levels of this potent dilator to ensure adequate blood flow.

2.     Nitric oxide production is enhanced every time there is an increase in blood flow through the facial skin: This is one of the most exciting aspects of nitric oxide physiology.  Every time blood flow is enhanced through skin blood vessels→the inside of the blood vessel wall ‘senses’ the increased shear force across it→this triggers local production of nitric oxide →causing even greater blood flow.   Let me stress this point. No matter what the flushing trigger is (i.e., heat, exercise, stress, skincare products, neural triggers, environmental insults, embarrassment, foods, beverages, etc.), every time that a flush occurs → facial blood vessels ‘sense’ this increase in blood flow → this triggers increased production of nitric oxide from the wall of the blood vessel → significantly increasing the intensity and duration of facial flushing. Therefore, nitric oxide inhibitors could significantly reduce the frequency, intensity, and duration of most forms of facial flushing.

3.     Nitric oxide production is enhanced in areas of skin that experience chronic increases in blood flow: Over time, chronic increases in skin blood flow can enhance nitric oxide production in two ways: (1) It can increase the number of enzymes that produce nitric oxide, and (2) It can increase the sensitivity of nitric oxide release from these blood vessels.    Both of these changes can make facial flushing more frequent and intense. These findings are important because most rosacea sufferers experience chronic increases in facial blood flow.

4.     Nitric oxide production is enhanced in areas of skin where physical damage has occurred to blood vessels: In vascular disorders where there is physical damage to the blood vessel wall, nitric oxide production from the damaged vessel is greatly increased, resulting in substantial dilation.  These findings are clearly relevant to rosacea sufferers because most sufferers incur extensive structural damage to their facial blood vessels.

5.     Nitric oxide production is increased during exposure to external heat (local warming of  the skin): In a recent clinical study, “Role of Nitric Oxide in the Vascular Effects of Local Warming of the Skin in Humans”, Dr. Dean Kellogg and colleagues demonstrated that nitric oxide was a key mediator of skin flushing to local heating.  ⁽ In this study, they warmed small areas of human skin and demonstrated that they could block most of the heat-induced skin flushing by local nitric oxide blockade (intradermal injection of L-NAME).  Consistent with these findings, a study by Dr. Goldsmith and colleagues, “Inhibitors of Nitric Oxide Synthase in Human Skin”, also demonstrated that nitric oxide inhibitors could significantly reduce skin flushing to local warming. These findings are very exciting because many rosacea sufferers report uncontrollable facial flushing to warm environments.

6.     Nitric oxide production is enhanced during body overheating (i.e., increased internal body temperature): In a recent clinical study, “Nitric Oxide and Cutaneous Active Vasodilation during Heat Stress in Humans”, Dr. Dean Kellogg and colleagues demonstrated that nitric oxide is a key mediator of skin flushing during body heating.  Consistent with this, a second study found that increased internal body temperature triggers nitric oxide-mediated skin flushing. A third study demonstrated that thermoregulatory shunt vessels of the human skin produce significant concentrations of nitric oxide, and that blockade of nitric oxide from these vessels caused a significant decrease in blood flow.  Taken together, these findings indicate that nitric oxide inhibitors can reduce skin flushing to internal body heating, one of the most powerful triggers for rosacea flushing.

7.     Nitric oxide production is augmented during exercise: Multiple studies indicate that nitric oxide is a key mediator of exercise-induced skin flushing.   Although the body response to exercise is quite complex, nitric oxide inhibitors could greatly reduce the intensity and duration of facial flushing to exercise.

8.     Nitric oxide production is increased in areas of skin irritation (i.e., irritant or allergic dermatitis): Very recently, several human clinical studies have shown that nitric oxide is intimately involved in irritant and allergic dermatitis.    These findings are important to rosacea sufferers who experience facial flushing and irritation to topical skincare products. Is it possible that nitric oxide inhibitors could allow rosacea sufferers to use normal skincare products again?

9.     Nitric oxide production is augmented in areas of skin that are exposed to sunlight (UV radiation): In a clinical study, “Inhibitors of Nitric Oxide Synthase in Human Skin”, Dr. Goldsmith and colleagues demonstrated that nitric oxide inhibition significantly decreased UVB-induced skin flushing. These researchers also demonstrated that this effect was long lasting (blood flow was reduced for over 24 hours).  This could be very helpful to rosacea sufferers, both in decreasing sunlight-induced flushing, and reducing the secondary damage that usually accompanies this inflammatory response.

10.     Nitric oxide production is increased during periods of stress: In a superb medical article on nitric oxide and skin disorders, Dr. Quereshi and colleagues state, “We have all experienced patients whose skin disease is exacerbated by stress.” These physicians speculate that stressful conditions stimulate nitric oxide release in the skin (through neural and hormonal stimuli), and that this in turn triggers increased skin blood flow and flare-ups.

Nitric Oxide Inhibitors Offer Tremendous Hope to Rosacea Sufferer
As the reader can see, nitric oxide could be one of the key mediators in facial flushing, skin redness and rosacea progression. Blocking the release of nitric oxide from facial blood vessels could markedly reduce all rosacea symptoms and triggers and lead to remission in many cases.

Nitric Oxide Inhibitors for Different Nitric Oxide-Producing Enzymes
Nitric oxide is generated by a group of enzymes called nitric oxide synthases.  Medical researchers have identified three basic nitric oxide synthases:

• Constitutive nitric oxide synthase – which is found in the walls of blood vessels and skin cells.

• Inducible nitric oxide synthase – which can also be found in the walls of blood vessels and skin cells.

• Neuronal nitric oxide synthase – which is only found in nerve endings.

Although each enzyme produces the same end product (nitric oxide), they are all unique in structure and function. Therefore, one blocker does not effectively block all of the nitric oxide synthases.  Recently, biomedical researchers have developed specific blockers for each group of enzymes. The most important advancement is in the selective blockade of inducible nitric oxide synthase which is primarily involved in flushing and inflammation.

Kalypsys Biotech with Major Breakthrough: Topical and Oral Treatments that Selectively Block Inducible Nitric Oxide Synthase are in Human Clinical Testing and Show Excellent Promise for Rosacea

Topical Inducible Nitric Oxide (iNOS) Inhibitor in Phase IIC Testing

Kalypsys is developing molecules that target inducible nitric oxide synthase, a member of the nitric oxide synthase (NOS) family of enzymes. The NOS family consists of three related enzymes (iNOS, eNOS and nNOS), each functioning in distinct physiological processes. Nitric oxide (NO) generation via the inducible nitric oxide synthase (iNOS) pathway has been implicated in the pathophysiology of skin inflammation, redness, dilation, flushing and skin pain syndromes.  The current clinical testing is focused on various painful skin conditions and has strong theoretical application for rosacea treatment.

Dr. Paul Grant, MD, Chief Medical Officer of Kalypsys is excited by the clinical results thus far on suppressing skin pain sensations, inflammation, hyper-sensitivity, redness and flushing in areas of inflammation.  He also realizes that there are multiple applications for this topical gel treatment including rosacea, inflammatory skin disorders, cardiovascular disorders and pain syndromes.  These will be in the treatment pipeline soon.

Dr. Grant and his team are also in the process of developing an oral  nitric oxide synthase inhibitor (KD7332) that blocks inducible nitric oxide synthase (nitric oxide produced during inflammatory states) and neuronal nitric oxide synthase (nitric oxide released from specific nerves located in the skin).  KD7332 is an oral iNOS/nNOS dual inhibitor under development by Kalypsys Biotech.   This new oral treatment holds great potential for rosacea because it not only blocks inducible nitric oxide synthase in areas of skin inflammation, but it suppresses the release of nitric oxide from nerves surrounding skin blood vessels.  Nitric oxide-containing nerves surround all blood vessels in the facial skin and are powerful controllers of local blood flow.  Nerve-derived nitric oxide is a one of the strongest dilators and is a potent stimulator for rosacea flushing and nerve-based flares.  Blocking neuronal nitric oxide is key towards reducing many forms of facial flushing and rosacea triggers.  This oral medication is now in clinical studies for various disorders.

Drug Blockade Illustration: The illustration above shows a cross section of a dilated rosacea blood vessel with red blood cells moving quickly through the center of the vessel… e.g. a rosacea flushing response.  It also shows where the new drug would bind – on the inner and middle walls of blood vessels where inducible nitric oxide synthase is most prevalent.  This is a selective topical medication that is quite potent and has a long treatment half life… this will be an excellent rosacea treatment in the near future.

The Race to get FDA Approval for a Topical Inducible Nitric Oxide Synthase Inhibitor is Heating Up
The development of topical and oral inducible nitric oxide inhibitors is one of the hottest areas of Pharmaceutical Research and Development for Dermatology, Inflammatory Skin Disorders, Skin Pain Syndromes, Cardiology, Diabetes and Generalized Inflammation-Based Disorders.  Currently, there are at least two other major Pharmaceutical companies testing topical and oral inducible nitric oxide synthase blockers.  Interviews with these two Pharmaceutical Companies will be finished and released in subsequent issues of our Rosacea Newsletter.

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Rosadyn-In-Focus: Three Proprietary Ingredients in Rosadyn Reduce Inducible Nitric Oxide Production

Oral Nutraceutical Extracts and Inducible Nitric Oxide Production
As a Micro-Vascular Physiologist who studied skin and vascular dilators most of my career, I realized in 2001, after multiple clinical trials, that rosacea was primarily a vascular disorder that needed to be treated by vascular-specific extracts with medicinal qualities.  Namely, I concluded that pharmaceutical-grade nutraceutical extracts that were able to reduce blood flow, suppress vascular inflammation and down regulate inflammatory enzymes, proteins and peptides in rosacea-affected skin would be central to rosacea clearance and recovery.

In the bio-medical lab in which I worked, we had access to countless medical treatments and ‘phyto-medicinal’ extracts of plant origin to test on various inflammatory skin models.   It became clear that nitric oxide, a potent dilator involved in all inflammatory skin disorders, was one of the best targets for rosacea treatment.  In fact, suppression of Inducible Nitric Oxide and down regulation of its enzyme (e.g. reduction of the number of proteins that synthesize and release nitric oxide) reduced the symptoms and severity of almost all inflammatory conditions, rosacea included.

Confirming my initial hypothesis, dozens of scientific and clinical studies between 2006 through 2009 demonstrated that oral Nutraceutical extracts such as Sulforaphane and Pycnogenol had the strongest inhibitory action on inducible nitric oxide and had potent vascular-specific actions.  These were the two powerhouse extracts for rosacea, and became a focus of my ongoing research.

Sulforaphane Reduces Production of Inducible Nitric Oxide
Sulforaphane is a phyto-chemical compound that was identified in broccoli sprouts by medical scientists at the Johns Hopkins University School of Medicine in Baltimore, MD.   Sulforaphane is classified as a phytonutrient and possesses strong anti-inflammatory, antioxidant and reparative actions in the skin.  More importantly, it interacts with blood vessels and their enzymes on many different levels to support proper functioning, strength, repair, protection, blood flow and growth, and recovery.

• In a clinical study published in “The Journal of Pharmacology and Experimental Therapeutics”, Dr.  Killeen and colleagues demonstrated that Sulforaphane inhibited nitric oxide production in inflammatory conditions in a dose-dependent manner — the higher the dose of Sulforaphane, the greater the nitric oxide suppression.   During this testing, a half dozen other potent compounds were tested and Sulforaphane was the most effective blocker of inflammation-induced nitric oxide production.  They concluded that Sulforaphane should have excellent therapeutic actions in any vascular disorders that involved overproduction of nitric oxide or uncontrolled vascular inflammation.

• In a 2010 clinical study published in “Mediators of Inflammation”, Drs. Tsai and Liu demonstrated that Sulforaphane is a potent inhibitor of inducible nitric oxide synthase… one of the most potent natural compounds available, rivaling the efficacy of evenprescription drugs.  They also stressed that Sulforaphane’s suppressive actions on nitric oxide were especially important during inflammatory events – a primary modulator of blood flow, flushing and inflammation.

• In agreement with the above findings, an excellent 2010 review article in “Alternative Medicine Review” highlighted that Sulforaphane was the most potent inhibitor of inducible nitric oxide synthase studied to date and has significant anti-inflammatory actions and anti-angiogenesis actions due to its ability to block inflammatory nitric oxide production.

Sulforaphane Blocks DNA Replication of Inducible Nitric Oxide Producing Enzymes: Sulforaphane not only suppresses the release of inducible nitric oxide production, but, over time, it reduces the number of nitric oxide synthase enzymes in blood vessel walls by blocking protein production at the DNA level.  This is the best method to reverse rosacea symptoms and break the chronic inflammatory cycle seen in rosacea because it reduces the number of enzymes that can produce excess nitric oxide and tempersthe skin’s “inflammatory signal”.  This is one of the single best ingredients for the treatment of vascular rosacea and associated flushing, and explains its prominence in Rosadyn’s active ingredients.

Buyer Alert: (1) Are you taking the right type of sulforaphane extract?  This is crucial towards achieving the best therapeutic effect, since three-day old sprouts have up to 100 times the sulforaphane of mature sprouts.  Moreover, the method of extraction matters, as supercritical carbon dioxide extraction provides a far purer, more bioavailable form of sulforaphane.  (2) Are you taking enough sulforaphane to saturate your facial blood vessels?  Many supplements only include one to two milligrams of sulforaphane and very few have more than 10 mgs… this is not enough to make an impact on rosacea redness, inflammation and flushing.  To inhibit nitric oxide overproduction you need to take the recommended clinical dose of 40 mgs.  Rosadyn uses BroccoRaphanin which is derived from the purest form of sulforaphane glucosinolate extracted from three-day old sprouts and includes 40 mgs per serving, which is the highest clinical dose available.

Pycnogenol Oligomeric Proanthodins (OPC’s) Reduces Production of Inducible Nitric Oxide
Pycnogenol or Pine Bark Extract is one of the best extracts for strengthening blood vessels, protecting blood vessels from damage, repairing blood vessel walls, reducing fragility and leakiness, and is also a potent inhibitor of inducible nitric oxide.  The primary active ingredient in Pine Bark Extract is Oligomeric Proanthodins (OPC).  OPC’s are small peptide fragments that insert themselves into the wall of blood vessels andexert their vasculo-protective effect.

• In a recent clinical study published in “Free Radical Biology and Medicine” (2009) medical investigators found that oral treatment with 95% OPC Pine Bark extract for six months lowered inducible nitric oxide synthase activity by an average of 80% in all testers with vascular inflammatory disorders including rosacea.  This is a medical-grade response typical of a pharmaceutical!  Biopsies performed after the completion of the study showed that the inflammatory nitric oxide enzyme was at near-normal levels and in many cases, OPC treatment broke inflammatory cycles that had been with these patients for years.

• In a clinical study involving 122 patients, Pycnogenol treatment for five months significantly reduced blood flow and flushing to various areas of inflamed skin.  Upon further research it was found that inducible nitric oxide synthase was the primary cause for increased blood flow, flushing and skin inflammation.  Pycnogenol treatment at clinical doses suppressed and normalized this overactive enzyme.  In follow up questionnaires six months later, 92% of the testers considered themselves in remission, demonstrating the long-term benefit of OPC treatment.

• Dr. Virgili and colleagues from the Department of Molecular and Cell Biology, UC Berkeley, recently demonstrated that OPC’s taken from pharmaceutical-grade Pine Bark Extract reduced inducible nitric oxide synthase in human inflammatory conditions (including inflammatory skin disorders) and it did this primarily by blocking the genetic material used to build DNA and new nitric oxide synthase enzymes.  These are exciting findings and directly relevant to rosacea treatment.  OPC’s basically put a break on inducible nitric oxide production at the genetic level and allowed the blood vessels and skin to recover.

Buyer Alert: Pycnogenol and Pine Bark Extracts have been the number one selling supplement for the last few years due to its endless list of vascular and skin benefits.  However, please be extremely cautious before purchasing any OPC or Pine Bark Extract, especially since this is a VERY expensive product given the rare pine bark that must be selected to ensure the highest OPC content.  In addition, the extraction and purification methods necessary to yield pharmaceutical grade quality further increase the price.  Despite the high price tag, most Pine Bark Extract supplements are unfortunately not bioavailable and do not have any clinical actions in the human body because they cannot be absorbed.  Notably, the Internet has been saturated by low quality pine bark extract from China and India that are essentially just pure bark and therefore little more than a good source of fiber.

In fact, the discoverer of OPC’s, Dr. James Masquelier, conducted a study wherein he purchased 30 OPC/Pine Bark Extract supplements and put them through vigorous testing.  Shockingly, he found that 28 out of 30 brands had no physiological or biochemical effect due to the poor quality and extraction methods of the OPC’s.  Indeed, most manufacturers still use inexpensive alcohol purification methods which damage the OPC’s and render them inert and ineffective in the human body.  As such, it is vital the Pine Bark Extract you take has 95% OPC content, is listed as “Pharmaceutical-grade” and has been tested in clinical studies.  That is the only way to ensure you are getting the right OPC formula.  Our Rosadyn formula incorporates the newest White Pine Bark Extract, is standardized to 95% OPC content, is pharmaceutical grade quality, is highly bioavailable and proven in human clinical studies.

It is also vital to take the appropriate dose, as only the clinical dose of 200 mgs has been shown to properly saturate all blood vessels in the skin.  As you will note, many Pycnogenol or Pine Bark Extract supplements only include 25 to 50 mgs of OPC which is not nearly enough to have a physiological effect on inducible nitric oxide synthase.  Rosadyn has incorporated 200 mgs of 95% OPC, Pharmaceutical-grade White Pine Bark extract into each serving.  Importantly, our extract has been isolated and purified without the use of alcohol or harsh solvents.

Synergism of Sulforaphane and OPC: While both Sulforaphane and OPC’s block inducible nitric oxide synthase and help break the vascular inflammatory cycle and flushing, each has a different mechanism of action… and each compliment the other extract in a synergistic action.  This is a very important combination and precisely the reason we include both, at their appropriate clinical doses, in Rosadyn.

Rosadyn’s Phospholipid Complex Delivers Sulforaphane and OPC’s Deep into the Wall of Blood Vessels
One of the best additions to our Rosadyn formula is our proprietary Phospholipid Complex.  Many companies overlook or do not understand that once an active ingredient is in the blood stream it still needs help to enter the phospholipid  membranes of blood vessel cells.   In order to do this the active ingredient must be complexed with a phospholipid.  Rosadyn’s Phospholipid Complex allows Sulforaphane and White Pine Bark OPC’s to be delivered to all three layers of the blood vessel wall (e.g. the inner wall, middle wall and outer wall).  This is important to emphasize because high levels of inducible nitric oxide synthase are found in all three layers… without phospholipids the active ingredient will only reach the inner layer of the blood vessel, resulting in subpar efficacy

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From The Desk of Dr. Nase: Rosacea & Rosadyn Treatment Case Study

Rosacea Case Study:  Mark W. from Dallas, Texas
Rosacea Subtype Workup: Vascular Rosacea with Strong Neural Component (Intense Flushing, Blushing & Burning)

“My name is Mark and I had severe rosacea for the past 16 years of my life.  The worst thing besides the redish and sometime purple appearance is the debilitating burning sensations.  I’ve had 3 ETS surgeries and close to 75 IPL treatments with limited success.  I’ve also used every prescription topical and oral treatment out there with no success.  I’ve been taking Rosadyn for about 6 months now and have recently increased to a higher dosage and my facial flushing and heat flashing and debilitating burning have never been better!  I don’t flush anymore and my skin is a normal pale color.  This is hands down the BEST rosacea treatment I’ve ever come across.  I continue to improve and consider myself in complete remission.  This product has changed my life.”

- Mark W, Dallas TX

Mark W. from Dallas, TX: Severe Rosacea Sufferer for 16 Years

Symptoms: »     Severe Facial Redness »     Intense Facial Blushing »      Chronic Burning Sensations »     Numerous Rosacea Triggers »     Classified as “Untreatable Rosacea” Treatment Failures: »     Over 70 Laser & IPL Treatments »     Every Oral and Topical Medication »      Most OTC Treatments »     Three ETS Surgeries Rosadyn Success: »     Redness & Flushing Cleared »     Burning Sensations Reduced »      Rosacea Triggers Under Control

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Rosacea Skin Care Central: Buyer Beware – Facial Cleansers with Scrubs and Micro-Beads

Common Scrubbing Beads found in Over-the-Counter Facial Skin Care Products
Face scrubs are facial washes that are designed to get rid of surface skin cells, unclog pores, smooth the skin’s surface and create a brighter complexion.  They are excellent for anti-aging, acne, clogged pores and overall skin complexion.  While these active ingredients are good for normal skin, they are contraindicated for rosacea skin due to their side effects on sensitive, thin skin.

Polyethylene Beads

Plastic beads are the most popular scrubbing ingredients in facial scrubs and cleansers.  Read the ingredient label of your facial cleansers for “polyethylene beads” or “oxidized polyethylene beads”.

Aluminum Oxide

Aluminum oxide is composed of crystals. It can be found in many over-the-counter facial cleansers and is used  in professionally administered microdermabrasion treatments.

Jojoba Beads

Jojoba beads are plastic beads filled with jojoba oil.  While these might be more gentle than most, they are still a major source of skin irritation and hyper-reactivity.

Ginko Biloba Beads

Ginko Biloba Beads are plastic beads filled with Ginko extract.  These are not only irritating, but Ginko Biloba is a topical dilator.

Oxygen and Hydrogen Peroxide Releasing Beads

Many products now incorporate oxygen and hydrogen peroxide into plastic beads to stimulate blood flow (which is good for non-rosacea sufferers but bad for rosacea sufferers).

Side Effects of Scrubbing Beads:

• Microscopic scratches on your skin’s surface that cause long-term physical damage
• Thins the epidermis resulting in a weakened and porous outer layer of facial skin
• Causes an immediate inflammatory response whereby the epidermis release inflammatory dilators onto blood vessels and nerves in the underlying dermis
• Causes a delayed inflammatory response whereby rosacea sufferers flush much easier to internal and external triggers because blood vessels are now inflamed and primed to flush

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Advice on Suppressing Rosacea Triggers: Melatonin Supplement to Reduce Night-Time Internal Body Heat

What is Melatonin
Melatonin is a naturally-occurring hormone that is secreted by the pineal gland, which is in an area of the brain called the hypothalamus.  Melatonin is produced from the amino acid called tryptophan and can be found in the blood as well as in the cerebrospinal fluid that bathes the brain and spinal cord. As a hormone, it conveys signals to other organs and is documented to help regulate the circadian rhythm and temperature of the body.

Melatonin’s Effect on Internal Body Temperature
In a series of clinical studies in the Journal of Applied Physiology, Dr. Cagnacci and colleagues found that melatonin supplementation reduced internal core temperature (e.g. body heat) by up to 0.5 degrees Celsius in most human test subjects.  This is a significant drop in internal core temperature and is equivalent to dropping room temperature from 85 degrees Fahrenheit to 75 degrees F. – a significant drop of this extent would help reduce night-time redness and flushing as it would allow the flushing center of the brain (the anterior and posterior Hypothalamus) to calm down and suppress nerve signals for facial flushing.  Over the years, several dozen clinical studies performed by Physicians and Naturopaths support this ground-breaking work.

• In a follow-up medical publication titled, “Melatonin: a major regulator of circadian rhythm and core temperature in humans”, Dr. Cagnaccia and colleagues indicate that melatonin may also be used to suppress various forms of nerve and hormone-induced increases in core temperature such as those experienced by pre-menopausal and menopausal women due to its ability to decrease core temperature and circumvent the common flushing response to these hormonal changes.
• Additionally, in a clinical study published in The Journal of Physiology, Dr. Gilbert and colleagues found that treatment with 1 mg of melatonin during the day reduced body temperature in all subjects… especially when body heat was the highest in the late afternoon/early evening.  This could be especially useful for those rosacea sufferers who experience late afternoon flushing due to natural elevations in body temperature.  In subsequent studies, Drs. Reid and Dawson performed a Double-blind placebo-controlled study on the effect of melatonin on body temperature during the day and night.  They also found that melatonin supplementation reduced body temperature during the day and also increased sleep duration at night due to melatonin’s hypothermic effect (e.g. ability to decrease body temperature).

In many studies, 0.5 to 2 mgs of melatonin supplementation during the day resulted in significant body heat reduction for several hours and at night 2.5 mgs to 10 mgs of melatonin reduced internal core temperature throughout most of the night.  As melatonin is a natural hormone produced by the brain, and may cause mild side effects, please discuss any day or nighttime supplementation with your physician or endocrinologist.

Sublingual Melatonin and Prescription Melatonin

Sublingual Melatonin: Sublingual melatonin is the best form to take because it’s immediately absorbed under the tongue by large veins and goes right into the systemic blood circulation.  This makes it much more effective, quicker acting and bypasses the stomach acid which degrades and inactivates up to 40% of oral melatonin tablets or capsules.  Clinical studies indicate that 1 to 2 mgs during the day is a reasonable dosage while a higher dose of 2.5 to 10 mgs may be required at night.  To find the right dose you will need to test various doses under the supervision of your physician.  My favorite sublingual supplement is made by Source Naturals –  Refer to the photo on the left.  Sublingual melatonin will have a positive synergistic action when used in conjunction with Rosadyn’s Hypothalamic Support Blend™:  PharmaGABA, L-Theanine and Phospholipid Carriers comprised of Phosphatidyl Choline and Phosphatidyl Serine.

New Prescription Melatonin Analogue: The prescription drug Rozerem (ramelteon) is a melatonin analogue that selectively binds to the melatonin MT1 and MT2 receptors.  This new film-coated tablet is more effective than over-the-counter Melatonin supplements due to its ability to bind to MT1 and MT2 membrane-bound receptors located is specific regions of the brain.  This medication is also longer acting than over-the-counter melatonin supplements — even the sublingual formulations by Source Naturals – and thus may be worth discussing with your primary care physician or endocrinologist.  The normal prescription strength dosage for Rozerem is 8 mgs at night but may be adjusted according to its use.

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Rosadyn Promotion: Receive a Free Bottle of Rosadyn with any Purchase of 3, 6 or 9 Bottle Packs

Vascular Health Specialists is offering a limited-time promotion on the purchase of Rosadyn.  Purchase any multi-bottle pack of Rosadyn (e.g. 3, 6, or 9-Bottle Packs) and receive a free bottle of Rosadyn.  To take advantage of this special offer, please click on the following link Rosadyn Offer and enter  “FREEBOTTLE”  into the coupon box. But don’t delay; this offer is only valid for one week, until March 3rd, 2011.

Remember, Rosadyn is backed by our unconditional 6-Month, Money-Back Guarantee… “See Visible Results or Receive a Full Refund”.  Unlike most rosacea products which offer a simple 30-day guarantee, or expensive laser treatments and medical prescriptions that offer no guarantee, we’re so confident that Rosadyn will help improve your symptoms and triggers that we offer Six Full Months to try Rosadyn, risk free. If you’re not completely satisfied with the results, we’ll refund your order… no questions asked!  This is a truly unique offer that is unprecedented in the rosacea treatment industry.

Future Publications of the Rosacea Newsletter and New Posts on the Rosacea Treatment Blog

We are committed to publishing fresh, novel content on living with and treating rosacea. To ensure you never miss a single newsletter or blog post, please enter your name and email address in the sign-up box below and follow us on Twitter at: http://twitter.com/RosaceaDr.

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Vascular Health Specialists LLC

We hope you enjoyed the first issue of our Rosacea Newsletter and find it useful in your battle against rosacea.

Sincerely,

Dr. Geoffrey Nase

Rosacea Research Specialist and Former Rosacea Sufferer

Dr. Patrick Bitter Sr.

Dermatologist and Rosacea Treatment Specialist