Life Extension Magazine®

Woman with clear skin using topical alpha-arbutin

Fade Unsightly Skin Pigmentation

Increased output of the skin’s melanin can eventually produce uneven pigmentation that makes skin appear older. Topical application of three compounds can lighten “age spots” and produce a more uniform—and younger-looking—complexion.

Scientifically reviewed by: Dr. April Parks, MD, MS, in August 2023. Written by: Rober Goldfaden and Gary Goldfaden, MD.

Age spots and brown-gray discolored patches contribute to the loss of youthful-looking skin.

Hyperpigmentation is a common dermatologic concern that arises from excessive production of the skin’s main pigment, melanin.1,2

In this article, you’ll learn about three compounds that successfully interfere with multiple stages of melanin synthesis to inhibit or reverse common pigmentation disorders.

A novel skin topical applicator has been designed to deliver these beneficial compounds in a safe, consistent, and uniform fashion to the target area, leaving behind a lighter and more luminous skin tone characteristic of a youthful appearance.

Targeting Multiple Stages of Melanogenesis

Targeting Multiple Stages of Melanogenesis  

Your skin normally produces the pigment melanin in specialized cells called melanocytes to mitigate the skin aging effects of the sun.3,4

With chronic sun exposure, however, melanocytes become hyperactive and release too much melanin that manifests as unsightly age spots and dark patches on the skin.5 Other factors such as heredity and hormonal changes can also lead to abnormal melanin output as we age, resulting in pigmentation disorders like melasma.6

While melanin formation (melanogenesis) at the cellular level is a highly complicated process characterized by numerous chemical reactions, it can be broken down to three major stages:

  • Stage 1: Binding of melanocyte-stimulating hormone (a-MSH) to the receptor melanocortin 1 receptor (MC1R).7
  • Stage 2: Conversion of L-tyrosine into dopaquinone by the key enzyme tyrosinase. Subsequent chemical reactions transform dopaquinone into melanin.8
  • Stage 3: Transfer of melanin-filled melanosomes to keratinocytes located in the epidermis.9

Most commercial skin lighteners contain ingredients that only target one stage of the process, producing some improvements in skin discoloration.

Researchers have now identified three compounds that work together to inhibit multiple stages for a more profound skin lightening effect.


The binding of melanocyte-stimulating hormone to the melanocortin 1 receptor sets in motion melanogenesis by activating tyrosinase in melanocytes.10

A novel peptide called nonapeptide-1 competes with a-MSH for binding to the melanocortin 1 receptor, which in turn prevents further activation of tyrosinase and thus the signal to turn on melanin output. This was confirmed in a lab study in which nonapeptide-1 reduced melanin synthesis in melanocytes by 33% without affecting their normal functions.11

Rumex occidentalis Extract

Human studies indicate that Rumex occidentalis, a plant native to the northern Canadian Prairies region, slows down the activity of tyrosinase to treat different forms of hyperpigmentation. In one such study, topical application of Rumex occidentalis extract reduced age spots by 15% after three weeks, and by 25% after six weeks compared to baseline.12,13

Melasma is a difficult-to-treat pigmentation disorder that predominantly affects women.14,15 In a randomized, double-blind, placebo-controlled trial, Rumex occidentalis extract was found to be as effective as the gold-standard skin-lightener hydroquinone in the treatment of melasma.16 This is noteworthy, since Rumex occidentalis extract offers a viable alternative to hydroquinone without its numerous side effects.17 Other research supports the efficacy and safety of Rumex occidentalis extract for lightening skin discoloration in melasma patients.18

Remarkable Skin Lightening Effects in Humans

The combination of nonapeptide-1 and Rumex occidentalis extract has shown a synergistic effect in clinical studies, leading to clearer skin than seen with either compound alone.

Scientists evaluated the impact of a topical cream containing these two compounds, along with niacin, shea butter, and vitamin E on 26 human volunteers with hyperpigmentation.19 Participants applied the cream once daily for six weeks. Numerous skin parameters were measured at baseline, at three weeks, and again at six weeks.

At the study’s end, researchers observed a 20% decrease in melanin production in 96% of subjects. This translated to a significant reduction in the number of UV-induced age spots and brown spots, as well as decreases in skin redness and ruggedness. Significant improvements in skin moisture, elasticity, and smoothness were also documented, leaving participants with healthier and more radiant-looking skin. The topical formulation was well-tolerated and restored alignment of skin color in 92% of participants.19

In a larger study involving 50 women, participants who applied a topical cream containing nonapeptide-1 and Rumex occidentalis extract twice daily for four weeks showed the following improvements:11

  • Reduction in dull complexion by 92%
  • Reduction in yellowish appearance by 86%
  • Reduction in age spots by 78%
  • Increase in evenness of skin tone by 88%
  • Increase in skin lightness by 80%
  • Increase in skin brightness by 86%
What You Need to Know
Eliminate Hyperpigmented Areas of Skin

Eliminate Hyperpigmented Areas of Skin

  • Chronic sun exposure and other factors increase the skin’s output of melanin, leading to age spots, dark patches, and melasma.
  • Most commercial skin lighteners only target one stage of melanin production (melanogenesis), resulting in only minor skin improvements.
  • Researchers have found three compounds that inhibit melanogenesis at multiple stages of the process for more profound skin-lightening effects.
  • Numerous human studies demonstrate that nonapeptide-1, Rumex occidentalis extract, and alpha-arbutin safely fade common forms of hyperpigmentation, often in only a few weeks.
  • These beneficial compounds can now be delivered in a unique topical skin applicator to hyperpigmented skin, leaving behind a more uniform and lighter skin complexion.


Like Rumex occidentalis, alpha-arbutin possesses strong inhibitory effects on tyrosinase. When tested against other popular skin lighteners in a 4-week study, alpha-arbutin exhibited 20% and 60% higher depigmenting activity than kojic acid and hydroquinone, respectively. And in a three-month study, researchers found that alpha-arbutin diminished the appearance of age spots in 85% of participants.20

Development of an Innovative Skin Applicator

Nonapeptide-1, Rumex occidentalis extract, and alpha-arbutin have been combined into one formula that now can be delivered directly onto your skin by a novel topical applicator.

This easy-to-apply, no-waste skin applicator was designed to specifically target darkening areas of concern on the face, neck, décolleté, arms, and hands. It delivers a precise dosage of this new formula across the entire surface of the hyperpigmented area in a consistent and uniform manner to safely lighten skin tone.


The abnormal output of the skin’s main pigment melanin over a prolonged period produces uneven pigmentation that robs you of a youthful appearance.  

The abnormal output of the skin’s main pigment melanin over a prolonged period produces uneven pigmentation that robs you of a youthful appearance.

Solid scientific evidence shows that three compounds—nonapeptide-1, Rumex occidentalis extract, and alpha-arbutin—target multiple stages of melanogenesis to substantially slow down melanin output to inhibit or reverse common pigmentation disorders such as age spots, dark patches, and melasma.

These beneficial compounds can now be safely delivered directly onto your skin by a unique topical applicator for a clearer and more even complexion.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

Gary Goldfaden, MD, is a clinical dermatologist and lifetime member of the American Academy of Dermatology. He is the founder of Academy Dermatology in Hollywood, FL, and Cosmesis Skin Care. Dr. Goldfaden is a member of Life Extension’s Medical Advisory Board.


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