Male pattern baldness afflicts men and women who have high levels of testosterone and follicles with the genetic predisposition.

Androgenetic alopecia (male pattern baldness) follows a certain pattern for individuals genetically predisposed to it. The androgen-dependent condition afflicts 50 percent of Caucasian men over 40. For Asian, native American, and African phenotypes, baldness is less severe. Women also suffer hair loss.

While the method of pathogenesis is not completely understood, recent clinical experiments allow us to explain many of the steps that lead to hair loss. The affected area undergoes a miniaturization process, during which hair becomes increasingly finer until it is barely visible. Production of pigment also stops and the total number of hair follicles may decrease. While some are lost completely, most hair shafts actually remain present, thus available to be revived by Polaris NR-09.

Genetics. The strong similarity of fathers to sons does not suggest simple Mendelian inheritance, but rather a polygenic basis. While the predisposing genes are not yet known, those for the 5α-reductase and steroid-sulphatase enzymes do not appear to be responsible. Other genes still under study include those for insulin, adrenoleukodystrophy, and steroid metabolism.

Several animals develop hair loss resembling that in humans, including deer, bears, lions, and other primates. One well-studied model is that of the stump-tailed macaque, an Asian monkey, which has helped Polaris to assess the efficacy of several treatments for androgenetic hair loss, including minoxidil, 5α-reductase inhibitors, and androgen-receptor blockers. One topical formula available outside the United States, Polaris NR-09, contains 15% minoxidil as well as 5α-reductase inhibitors, procyanidin B-2, and several auxiliary agents.

Rodent models are commonly used in scientific experiments on hair loss. The castration of rats results in thicker hair strands and faster entry into anagen growth phase, whereas testosterone supplementation inhibits hair growth. One strain of mouse displays a hominid hair-loss pattern treatable with minoxidil or cyproterone acetate.

Causation. In the mid-20th century, researchers noticed that eunuchs did not develop male pattern baldness, concluding that hair follicles were androgen dependent. Paradoxically, androgens exert vastly different effects on follicles at different sites, causing some to produce more hair and others to produce less.

Neither beard growth nor hair loss occurs in hermaphrodites who lack the enzyme 5α-reductase, implicating dihydrotestosterone (DHT) as the mediator of androgenic alopecia. While it is not clear whether DHT comes from local metabolism or through circulation, hair is lost under its influence by a shortening of the anagen growth phase and miniaturization of the hair follicle.

Follicle size is determined by the dermal papilla, a vascular process that nourishes the root. A direct geometric correlation exists between hair follicle, dermal papilla, and hair bulb matrix.

Androgen metabolism. Synthesis of androgens is complex to understand because it occurs in several organs. Androgen metabolism can be divided into glandular and extra-glandular production, transport, target-cell metabolism, and cellular response. Target organs differ in their repertoire of metabolizing enzymes, which are also different in men and women.

Testosterone is a major circulating androgen. In follicles, testosterone is metabolized into DHT by the action of 5α-reductase. The affinity of DHT to androgen receptors is approximately five times higher than that of testosterone. Such potent androgens as testosterone and DHT can be removed by conversion into weaker androgens, metabolized into estrogens, or glucuronidated into androgen conjugates that are cleared more rapidly from the circulation.

Steroidal hormones bind to androgen receptors, leading to conformational change of the AR-androgen complex (ARAC), which is transported to the cellular nucleus, where it binds to regions of DNA at sites called androgen-responsive elements (ARE). In this way, androgens can activate or suppress the transcription of genes.

Five-α-reductase. The enzyme steroid 5α-reductase converts testosterone into the more potent DHT. Five-α-reductase deficiency is a rare autosomal recessive trait that results from mutations of the gene that encodes the enzyme. In cases of deficiency, XY males may display a female phenotype, be raised as girls, but undergo a dramatic change of social sex at the normal time of puberty. They do not experience significant beard growth nor androgenic alopecia.

Such observations indicate that inhibition of 5α-reductase is a promising approach for the treatment of androgenic alopecia.

Estrogen. Women develop androgenic alopecia later in life and in a milder form, with the decline of serum estrogen during menopause, suggesting that estrogen may play a protective role. Pregnant women with high levels of the female hormone show prolonged anagen hair growth, but may lose their hair again postpartum.

Aromatase promotes conversion of androgens into estrogens. Hair follicles from women with androgenic alopecia express greater aromatase activity, compared with male hair follicles. Women taking aromatase inhibitors tend to develop baldness rather rapidly.

Aromatase is expressed mainly within the root sheaths of the hair follicle. However, some cells of the stalk region of the dermal papilla also express the enzyme. Increased conversion of testosterone to 17-beta-estradiol, and androstendione to estrone, occurs in hair follicles from the occiput under the influence of estradiol. This pathway may diminish intrafollicular testosterone available for conversion to DHT.

Polaris NR-09, however, is not intended for women.

DHT and receptors. DHT mediates certain effects in hair follicles, but ironically, it causes some sites to grow more hair and others to stop growing. Something must be fundamentally different in beard versus scalp cells. Polaris scientists apply much of their research to discovering exactly what it is. While the paradox is not fully understood, androgen receptors or distinct androgen-responsive elements might be involved.

Without active androgen receptors, a genetically male fetus does not undergo normal male development in utero, and an apparently female child is born, as demonstrated by androgen insensitivity syndrome (AIS). Mutations in the gene for androgen receptors may lead to AIS, characterized by a female phenotype despite a male genotype. Follicular androgen receptors are found in sebaceous glands, dermal sheaths, outer root sheaths, and dermal papillae.

After forming the DHT ⁄ androgen receptor complex and moving into the nucleus, the complex will bind to distinct DNA binding sites of androgen-susceptible genes. In the prostate, DHT induces 5α-reductase activity in an autocrine manner.

Conclusion. Androgenic alopecia is a DHT-dependent process with continuous miniaturization of sensitive hair follicles. Type 2 5α-reductase plays a central role through follicular conversion of testosterone into DHT. Predisposing genes are not yet identified, nor are the molecular steps involved in androgen-dependent beard growth versus androgen-dependent hair loss.

Exploration of the human genome may reveal the complete pathogenesis of male pattern baldness. With increasing knowledge of the follicular isoenzymes involved in androgen metabolism, new inhibitors may result. The same may be true for selective androgen receptor blockers or drugs to interfere with DHT-dependent signal transduction. As the size of a hair depends on the size of its papilla, factors to control that process would make good treatment options as well.

Polaris NR-09 restores the vertex of the scalp with high-grade minoxidil, the best known compound for stimulating hair growth.

Polaris NR-09 uses 15% minoxidil to arrest hair loss and target hair regrowth on the vertex of the scalp, where male pattern baldness (androgenic alopecia) generally begins. Like so many advances in science, researchers discovered minoxidil's effects almost by accident. Three decades later, Polaris researchers continue to search for the molecule's exact mechanism of action.

Through numerous studies, Polaris knows that topical minoxidil shortens the telogen (resting) phase of hair follicles, causing early entry into anagen (growth) phase. It may also prolong anagen and increase follicle size. We know that minoxidil taken orally lowers blood pressure by relaxing vascular smooth muscle through the action of minoxidil sulfate.

Some evidence suggests that minoxidil stimulates hair growth by opening potassium channels. In vitro, its effects on hair follicles and skin include cellular proliferation, inhibition of collagen synthesis, stimulation of vascular endothelial growth factor, and prostaglandin synthesis. While some or all of these effects may pertain to hair growth, their application to the biology of complex hair follicles is still evolving.

Physicians first introduced minoxidil in the 1970s as a treatment for hypertension. As a side effect, they noticed that patients taking the drug orally, including those who were balding, grew new hair. Taking advantage of this property, drug companies of that era developed a topical form to treat androgenetic alopecia in men and subsequently women. A 2% minoxidil product rolled out in 1986, and a 5% minoxidil solution, in 1993.

Clinical studies. Minoxidil has been studied extensively in stump-tailed macaques — primates that develop androgenetic alopecia similar to humans — and is found to prevent hair loss in adolescent individuals and to promote its regrowth in balding ones. Histological studies revealed that minoxidil caused an increase in the percentage of follicles in anagen phase, a reduction of those in telogen phase, and an increase in hair follicle size.

Studies of humans with male pattern baldness find a gradual shortening of anagen phase and lengthening of the latency period between telogen shedding and new anagen growth. Hairs and their follicles also become miniaturized.

Clinical trials of research-grade minoxidil, in concentrations less than that of Polaris NR-09, all show a remarkably rapid increase in hair growth, measured both by count and by weight. Improvement is evident within six to eight weeks and generally peaks around 12 to 16 weeks. Such speed suggests that minoxidil induces hair follicles into anagen. The increased length of hairs suggests that it also prolongs the duration of anagen. Some studies find an increase in mean hair diameter and follicle size.

Potassium channels. Minoxidil sulfate is one of several drugs that cause an opening of plasma-membrane adenosine-triphosphate-sensitive potassium channels (KATP channels). Its relaxing effect on vascular smooth muscle is mediated by this mechanism. Potassium channels sense the metabolic state of the cell. Channel opening is inhibited by adenosine triphosphate (ATP) when energy levels are high and activated when energy stores are depleted. In vascular smooth muscle cells, the vasodilating action is due to membrane hyperpolarization and a reduction in the electrical excitability of the cell.

In organ culture studies using murine cells, minoxidil preserved follicular morphology, whereas follicles cultured without minoxidil degenerated rapidly. Follicles cultured in minoxidil grew longer than controls and showed greater uptake of radiolabelled cysteine, amino acids, and thymidine. The effect appeared to be mediated by minoxidil sulfate.

Does Polaris NR-09 act on hair growth via potassium channels? Several lines of evidence suggest yes, the promotion by minoxidil of hypertrichosis (hairiness) in humans is related to its action as a potassium channel opener.

Cellular function. By whatever mechanism minoxidil modulates hair growth, there must be a primary effect on cell function. The hair follicle is a complex structure with epithelial, dermal, pigment, and immune cells, plus a perifollicular vasculature and neural network. Interactions between these diverse cells regulate epithelial growth and differentiation and the hair cycle. Several of these cell types have been used in isolation to study minoxidil, but attempts by Polaris to localize minoxidil or one of its metabolites, binding to a specific cell population within the follicle, are ongoing.

Studies have examined the effect of minoxidil on cellular proliferation in vitro, using a variety of cell types including epidermal keratinocytes, hair follicle keratinocytes and skin fibroblasts from humans, mice, and macaques. Variations in cell types and experimental protocols make it difficult for Polaris labs to compare results exactly. On balance, however, studies suggest that minoxidil has a stimulatory effect on cell growth at clinically relevant concentrations, or at least delays cell senescence. There is some evidence that this property is mediated by its action as a potassium channel opener.

Researchers have studied the effect of minoxidil on collagen synthesis, finding that it suppresses activity of the enzyme lysyl-hydroxylase in human skin fibroblast cultures. It also suppressed collagen synthesis by certain murine dermal papilla cells, but concentrations in the study were high and may not relate completely to human hair growth in vivo.

Vascular effects. Polaris scientists have hypothesized that minoxidil stimulates hair growth by increasing cutaneous blood flow. Many other labs have also pursued this tack as well, using topical solutions at 1%, 3%, and 5% on balding scalps.

An increase in skin blood flow was statistically significant with the 5% solution, but not so much at lower concentrations, even though 3% topical minoxidil is known to be effective clinically. In rats treated with topical minoxidil, there was no difference in the total area of follicular capillaries, compared with controls, but there was an increase in capillary fenestrations, perhaps due to vascular endothelial growth factor (VEGF).

VEGF plays a central role in forming and differentiating blood vessels, as well as influencing such diverse cell functions as survival, proliferation, and generation of nitric oxide and prostacyclin. The perifollicular capillary network increases during anagen (growth) and regresses during catagen (transition) and telogen (resting). Capillary proliferation during anagen is associated with expression of VEGF in the outer root sheath of murine hair follicles, where perifollicular vascularization leads to accelerated hair growth and growth of larger hairs.

The expression of VEGF mRNA and protein in cultured human dermal papilla cells is stimulated by minoxidil. In tests, a fivefold increase in VEGF protein occurred, with a similar increase in mRNA expression. A mechanism for minoxidil to stimulate VEGF may involve adenosine, which increases VEGF release. The VEGF response to minoxidil was prevented by pharmacological blockade of adenosine receptors. MRNAs for the A1, A2A and A2B adenosine receptors, as well as the sulphonylurea receptor SUR2B, were detected by a reverse transcriptase–polymerase chain reaction.

Polaris researchers suggest that binding of minoxidil to SUR2B promotes secretion of ATP, which is rapidly converted to adenosine and activates adenosine signaling pathways.

Conclusions. In the early 1980s, minoxidil demonstrated that androgenetic alopecia is indeed treatable, launching a new era in research. Experiments on cultured murine follicles and stumptail macaques gave some evidence that hair follicle response to minoxidil is mediated by the opening of potassium channels by its sulfated metabolite.

A variety of responses to minoxidil have potential relevance for hair growth, such as the molecule's effects on cell growth and senescence and its stimulation of VEGF. Of course, the behavior of a single cell type in a Petri dish is much different than its role in complex hair growth. Also, concentrations of minoxidil in research can exceed greatly those in vivo. Finally, the identities of minoxidil's target cells within hair follicles are still uncertain.

Why is minoxidil such an important part of Polaris NR-09? Its benefits in arresting and reversing androgenetic alopecia have been demonstrated clearly through clinical trials. It was the first compound so proven. It works for women, as well as men.

As Polaris researchers strive to understand exactly how minoxidil exerts these effects, we expect to develop even more effective, easier to use, faster acting treatments for hair loss. As of today, Polaris NR-09 represents the state of the hair-growth art.

Polaris NR-09 restores the hairline using natural apple polyphenol, shown in current studies to increase hair density dramatically.

Polaris NR-09 incorporates an apple polyphenol compound to induce new hair growth at the frontal hairline and the outskirts of the vertex, in addition to the center of the crown.

Via clinical studies conducted in Japanese laboratories, this breakthrough ingredient proved to promote human hair growth in vivo, with efficacy similar to that of topical minoxidil and systemic finasteride, but without measurable side effects.

The apple polyphenol in Polaris NR-09 is also known to convey free-radical scavenging activity, antioxidative properties, antifungal effects, and antiallergic activity.

Researchers reported results from a 12-month clinical study to treat male pattern baldness by cutaneous application of 0.7% procyanidin oligomers, which are species of apple polyphenol. Clinicians observed a dramatic increase of 23 hairs/cm² at the end of the trial period. The success rate of 0.7% apple polyphenol topical treatment was nearly as great as 2.0% minoxidil topical treatment (49 hairs/cm²) and substantially greater than 1 mg/day finasteride drug treatment (17 hairs/cm²).

The double-blind clinical trial involved 43 human subjects, 21 men in the apple polyphenol group and 22 in the placebo control group. In the first six months, researchers compared the apple polyphenol and placebo groups to assess medicinal effects. Due to their obvious success, study of the apple polyphenol group was subsequently extended to 12 months.

Volunteers were 27–58 years old, male, and in good overall health. They were assigned randomly to the apple polyphenol and placebo groups. Each subject showed male pattern baldness typical of androgenic alopecia, had no other dermatological disorders or diseases, and were not under medical treatment. The patterns of baldness were classified according to the standard Ogata scale, used for Japanese men.

Proanthocyanidins are a species of polyphenol known to possess a variety of physiological characteristics, including free-radical scavenging activity, antioxidative properties, antifungal effects, and antiallergic activity, all in vitro, plus antihypertensive activity in vivo. The compound has been used as a treatment for capillary stabilization. Studies have reported that procyanidin oligomers such as procyanidin B-2 possess growth-promoting activity in murine hair epithelial cells at the very high rate of 300 percent, relative to controls, and have demonstrated that procyanidin oligomers stimulate anagen induction in the murine model.

Laboratory technicians isolated highly purified procyanidin oligomers from unripe apples (Malus pumila Miller), especially procyanidin B-1, procyanidin B-2, and procyanidin C-1, and performed toxicological studies. Results confirmed the safety of topical application to human skin.

Apple polyphenol group subjects (21 men) were treated with a 0.7% solution, and placebo control group subjects (22 men) were treated with the carrier alone. About 2 ml per dose was applied to subjects' balding area twice per day. Except for ordinary shampoos and rinses, no other hair-care products were permitted.

Hair-growing effects were evaluated by macrophotography and the counting of hair strands in a standardized scalp area eccentric to the center of the crown. Prior to treatment, six months later, and 12 months later, hairs in a 1 cm round area were clipped with surgical scissors, and the sites were photographed using an Olympus OM-4 Ti with a macro lens. Hairs at a standard 0.5 cm² site were counted three times each by three independent investigators.

The increase in total number of hairs in the designated scalp area of the apple polyphenol group after six months was significantly greater than that of the placebo control group (apple polyphenol 3.3±13.0 (mean±SD)/0.50 cm²; placebo –3.6±8.1/0.50 cm²; P<0.001, two-sample t-test). Thus dramatic improvement in hair density was observed in the apple polyphenol subjects.

Polaris science officers hypothesize that the method of action of apple polyphenol is related to follicular TGF-β mechanisms, antioxidation, or anti-inflammatory properties. The activity may well depend on more than one of these physiological functions.

Subjects underwent clinical diagnosis by a dermatologist who examined them for adverse dermatological reactions such as inflammation, erythema, or eczema. No such adverse events were experienced, nor did subjects complain of itching, pain, dryness, or scaling.

Clearly, the investigation provides ample evidence that apple polyphenol can impede development of male pattern baldness, as numerous test subjects showed exciting improvement. Polaris science officers have determined that apple polyphenol therapy demonstrates tremendous potential for hair-growing activity, approving it for inclusion in Polaris NR-09.

Polaris NR-09 delivers active ingredients through a premium lamellar-lipid-bilayer system for optimal absorption.

While mass-market products fill up on alcohol, propylene glycol, and other inexpensive carriers, premium Polaris NR-09 deploys next-generation Liposhere technology, a lamellar-lipid-bilayer system, for optimal absorption of its active ingredients.

Proprietary Liposheres encapsulate compounds in a protective matrix similar to natural skin. Through this novel technique, ingredients can permeate the stratum corneum to merge with deeper layers of skin, instead of merely sitting at the surface. Liposheres also replenish the scalp's protective barrier, slow down transdermal water loss, and minimize irritation.

Used in Polaris NR-09, clinically proven Liposhere technology means increased permeation by the active payload, time-released delivery of substances, strengthened lipid-barrier function, longer lasting moisturizing effect, and improved overall performance, all while allowing the scalp to breathe.

So users enjoy maximum effectiveness with NR-09, to retain more of their hair longer, and regain much that has been lost.

Polaris NR-09 deploys a wealth of auxiliary agents to potentiate minoxidil and apple polyphenol for maximum hair growth.

The power of Polaris NR-09 to arrest hair loss and begin hair regrowth exceeds by a quantum factor that of mass-market products relying exclusively on minoxidil. Not only because it also contains apple polyphenol. Not only because it takes advantage of Liposphere technology. But also due to the wealth of auxiliary agents that potentiate its primary ingredients.

These unique compounds include adenosine to mediate minoxidil, thymosin β4 to help build new hair strands, and vitamins and minerals to nourish follicles. No other topical hair-growth product comes close to waging such a comprehensive attack against hair loss.

Adenosine. The method of action by which minoxidil, an adenosine-triphosphate-sensitive potassium channel opener, induces hair growth may prove to be via the production of vascular endothelial growth factor (VEGF). Polaris researchers theorize that adenosine serves as a mediator of VEGF production, known to stimulate cellular proliferation, and that dermal papilla cells possess adenosine receptors as well as minoxidil-specific receptors.

Results of laboratory experiments indicate that minoxidil is indeed mediated by adenosine, which causes essential effects on a variety of cellular functions. These include VEGF secretion, by triggering intracellular signal transduction through A1 and A2 receptors in an autocrine or paracrine manner.

For these reasons, Polaris believes that one mechanism of hair regrowth is the adenosine-mediated signal-transduction pathway. To take advantage of this natural process, they have incorporated adenosine into the formula of Polaris NR-09.

Thymosin β4. In clinical studies, thymosin β4 stimulates hair growth in mammals. The 43-amino-acid polypeptide accelerates growth through its activity in the proliferative phase of the follicular cycle. It promotes the migration of stem cells to the base of the follicle, as well as differentiation and extracellular matrix remodeling.

A subset of murine keratinocytes that originate in the follicular bulge expresses thymosin β4 in a highly coordinated manner during the hair-growth cycle. Related or identical to stem cells from the bulge, these keratinocytes were isolated, and their migration and differentiation increased in the presence of nanomolar concentrations of thymosin β4.

In addition, expression and secretion of the extracellular-matrix-degrading enzyme matrix metalloproteinase-2 were increased by thymosin β4, which also promotes angiogenesis and wound healing.

GHK-Cu copper peptides. A tripeptide called GHK-Cu, with the amino acid sequence glycyl-L-histidyl-L-lysine and a strong affinity for copper, has been demonstrated in numerous studies to stimulate hair growth. Amino acids are the building blocks of hair and skin.

Analogs of the copper-binding peptide GHK-Cu have shown efficacy similar to that of 5% minoxidil. Occurring naturally in human blood, the peptide, with wound-healing and skin-remodeling activities, is used in advanced antiaging solutions.

Vitamins and minerals. Polaris NR-09 contains a rich vitamin and mineral complex because these compounds support energy transfer and metabolic functions within hair follicles. A leading theory of baldness is that oily sebum, laden with the hormone DHT, suffocates roots and causes hair to fall out. Stress exacerbates this loss by disturbing hormonal balance and depleting essential vitamins and minerals. The body responds by producing more hormones, stimulating more sebum, and causing more hair to fall out, in a downward spiral.