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Compound reverses hair loss, reduces hair whitening linked to fatty diets in mice

An experimental compound that prevents the production of glycosphingolipids (GSLs) reduced hair loss, hair whitening, and skin inflammation in mouse models. Feeding mice the man-made compound of D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) seemed to reverse such symptoms which have been linked to Western diets that are high in fat and cholesterol (Sci Rep 2018; 8(1):11463).

The findings shed light on possible pathways for addressing hair loss and skin wounds in humans with oral or topical medications. That being said, researchers emphasized that although the compound was efficacious in animals, it may not have the same benefits for humans.

“Further research is needed, but our findings show promise for someday using the drug we developed for skin diseases such as psoriasis, and wounds resulting from diabetes or plastic surgery,” said study author Dr. Subroto Chatterjee, PhD, professor of pediatrics and medicine at the Johns Hopkins University School of Medicine in Baltimore, in a press release.

Study methods

Dr. Chatterjee and his colleagues genetically modified a group of mice to have atherosclerosis. Then, the researchers fed one group of the mice a Western diet high in fat and cholesterol. The second group of mice was given standard food. All mice were fed their diets from 12 weeks of age to 20 weeks.

GSLs inhibited by D-PDMP are prevalent in keratinocytes and other cells that compose the epidermis. Investigators observed that mice fed a diet high in fat and cholesterol were more likely to have hair discolouration (from black to grey to white), substantial hair loss, and skin inflammation with multiple wounds.

Compared to those given standard food, the mice that ate a Western diet lost hair, formed skin lesions, and had hair whitening. These results became more severe when the mice continued eating a Western diet for 36 weeks. At that point, 75% of the mice had hair loss and multiple skin lesions.

Mice in both experimental arms were given different amounts of D-PDMP from 20 to 36 weeks of age, while they continued to eat the same diet. D-PDMP was given in either capsule or liquid form.

Mice that received 1 milligram and 10 milligrams of D-PDMP in a capsule per kilogram of body weight from 20 to 36 weeks while eating a Western diet, started regaining hair and hair colour. Their skin inflammation also lessened. Treatment with 1 milligram of D-PDMP in a capsule per kilogram of body weight was as effective as 10 milligrams per kilogram as a liquid.

Western diets and hair loss

Furthermore, the research team found that mice eating the Western diet experienced an infiltration of neutrophils in various skin areas. Treatment with capsulated D-PDMP reduced the number of neutrophils, implying reduced skin inflammation and wounding.

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The researchers also determined ceramide, glucosylceramide, and lactosylceramide levels in the mice. Ceramides help protect the skin’s moisture, and glucosylceramide is the first derivative of ceramide. In contrast, lactosylceramide—a later derivative of ceramide—activates inflammation.

Compared to mice fed normal food, those fed a Western diet had decreased total ceramide levels, decreased glucosylceramide, and nearly three times more lactosylceramide. Treatment with 1 milligram of D-PDMP in a capsule per kilogram of body weight or 10 milligrams of D-PDMP as a liquid per kilogram of body weight increased ceramide levels to normal.

“Our findings show that a Western diet causes hair loss, hair whitening and skin inflammation in mice, and we believe a similar process occurs in men who lose hair and experience hair whitening when they eat a diet high in fat and cholesterol,” said Dr. Chatterjee.

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