Topical Use of Nicotinamides

What other ingredients in skin creams work against skin aging? In medical research, placebo-controlled studies are the standard, but with cosmetic products they are still too rare. That raises questions about their effectiveness, and so many people buy only “hope in a jar.” Safety concerns also exist. To this day, cosmetics contain a whole series of toxic chemicals. Of the more than 12 000 synthetic substances used in cosmetics, fewer than 20 percent are recognized as harmless. Of course, that does not mean that natural ingredients are automatically harmless. Poison ivy is absolutely natural, yet you still wouldn’t want to smear it on your face. But there are relatively safe natural options, with varying effectiveness.

Nicotinamide (niacinamide) for topical use is a form of vitamin B3 that does not cause skin irritation and has been described as “one of the best-studied medical anti-aging agents,” but there appear to have been only three placebo-controlled human studies, which makes clear the state of research on medical skin-care products.

The main culprits behind photoaging of the skin are free radicals produced by UV radiation. With excessive sun exposure, sugars and proteins in the skin oxidize into a yellow-brown pigment that makes aging skin look sallow and doughy. Since nicotinamide is a precursor of two potent antioxidants, it is hoped that the oxidation process can be interrupted, as the first study on topically applied niacinamide showed.

It was a twelve-week randomized placebo-controlled clinical split-face double-blind study with middle-aged women. In a split-face study, each participant is her own control. The substance to be tested (in this case 5 percent nicotinamide in a moisturizer) is applied to one half of the face and the placebo (plain moisturizer) to the other, and neither the participants nor the researchers know which is which until the code is broken at the end. In this way, skin type and application technique are factored out, since different people apply facial products differently. Many people, however, apply cream to both halves of the face with the same hand. So if it is not explicitly required to wear different gloves or wash the hands after doing one half, cross-contamination can occur.

After twelve weeks, the wrinkles on the nicotinamide side of the faces were slightly reduced (by 5 percent), and spots, speckles, and sallowness progressed more slowly. A later publication also described improved skin elasticity. Nicotinamide achieves only about one fifth to one third as much as tretinoin, but it does not cause excessive skin irritation.

The other two studies used a similar split-face approach, but with 4-percent nicotinamide products. In one study, no significant effect on facial wrinkles was found compared with placebo, but in the other, which was limited to crow’s-feet around the eyes, there were significant improvements at the end of the study after eight weeks in both subjective and objective measurements. In 64 percent of the eye wrinkles on the nicotinamide side, a moderate or marked improvement occurred, compared with zero percent on the placebo side.

Topical Use of Vitamin C

If skin aging is caused by oxidative stress, then you could just apply antioxidants like vitamin C directly, right? Topical application of antioxidants can lead to a tenfold higher concentration in the skin than oral intake (at least in the skin of mice). A renowned plastic surgeon from Beverly Hills recently wrote in a report on topical anti-aging skin care: “At a minimum, patients should be advised to use sunscreen daily, a retinoid every evening, and apply an antioxidant topically every day.” But which antioxidant? Only one has been proven to work.

Vitamin E is ubiquitous in skin-care products, yet there is no evidence that it plays any role in skin aging at all—neither for wrinkles nor for age spots or skin texture—and the only study on topically applied CoQ10 found that it also does not work significantly better than a placebo. However, there is a form of vitamin C that has been shown to be effective.

From skin biopsy studies, we know that local application of a 5-percent solution of L-ascorbic acid (ascorbic acid, the vitamin C in foods) significantly increases collagen formation in human skin compared with placebos, suggesting that “the activity of dermal [skin] cells in postmenopausal women is not maximal and can be increased.” A split-face study in which three drops of a 10-percent L-ascorbic acid solution were applied for three months found clear improvements in fine and deep wrinkles, pallor, and skin tone (firmness) compared with the placebo side of the face. The participants did not know which side they had applied which to, but 16 of 19 (84 percent) correctly guessed, based on the improvements, which was the vitamin C side.

Unfortunately, L-ascorbic acid is unstable in creams. It turns an unattractive brown when it oxidizes, so it cannot be stored for long. Therefore, the skin-care industry instead uses more stable vitamin C esters or derivatives such as ascorbyl palmitate, ascorbyl stearate, magnesium ascorbyl phosphate, or ascorbic acid sulfate. Unfortunately, there is no evidence whatsoever that these variants work similarly well, presumably because they are poorly absorbed and scarcely convert into the active form. The good news is that you can make it yourself.

Although split-face (face), split-neck (neck), and arm studies have shown that vitamin C at concentrations of 3 and 5 percent works against wrinkles, at least 10 percent is recommended. 30 grams of the 10-percent solution in the study mentioned above costs an absurd 130 dollars. You can mix up a solution yourself by simply buying L-ascorbic acid as a powder and mixing 3 grams of it with 30 grams of water, which comes out to a cost of about 5 cents per 30 grams—1000 times less than the commercial product. All you need is a dropper bottle. Then you put four or five drops in the palm of your hand and apply them daily with your fingertips to the face, neck, and décolletage. But caution: the solution should not get into the eyes.

Alphahydroxy Acids

Fruit purées have long been used for facial masks, and for good reason. Alphahydroxy acids, that is, fruit acids, are added to chemical peels in high concentration, but lower concentrations are available over the counter. In see.nf/alpha I present the four placebo-controlled studies on the subject. In essence, alphahydroxy acids can help with existing sun damage, but they increase the skin’s sensitivity to light and thereby set up future damage.

Skin Cancer

Each year, more than a million new cases of skin cancer are detected; about one in three Americans is affected over the course of their lifetime. The risk increases with age, and the number of cases is rising. Should we therefore undergo regular full-body skin cancer screenings? The Skin Cancer Foundation recommends an annual check by a physician, but according to the official statement of the US Task Force for Preventive Services UPSTF, the evidence is not sufficient to justify regular skin examinations, no matter at what intervals. This is based in part on a nationwide experiment from Germany.