Allantoin: The Vitamin-Like Compound for Skin and Anti-Aging Benefits

Allantoin is a compound that occurs in aloe vera, chamomile, lotus, yam, and other plants.

Allantoin can also be chemically synthesized. Within the body, it acts as a free radical scavenger. 1



Allantoin Activity is Similar to a Vitamin

In an article published in 2004, E. P. Gus'kov and colleagues suggest that allantoin acts as a vitamin.

“Inactivation of the gene Uox in primates, which is responsible for the synthesis of the enzyme uricase, has determined new ways of social and intellectual evolution of mammals,” they observed. “Almost simultaneously with this process, a mutation occurred, as a result of which primates lacked the capability of endogenous synthesis of ascorbate. These mutations sharply changed the systems of antioxidant defense by eliminating vitamin C and allantoin from the overall profile of intracellular nonenzymatic inactivation of reactive oxygen species.”2

The authors discuss the ways in which allantoin behaves like a water-soluble vitamin. They note that in water solutions, the antioxidative properties of allantoin and ascorbic acid are similar, suggesting that allantoin could be regarded as a vitamin.

Allantoin, Wound Healing, and Skin Health

Research has revealed a benefit for allantoin in wound healing.3 When combined with other compounds, it has been shown to help prevent intra-abdominal adhesions after surgery and reduce redness and the formation of new blood vessels in hypertrophic scars and keloids, which was associated with improvement in skin lesions.4,5

“Allantoin, 5-ureide-hydantoin, has been widely cited in literature as holder of numerous pharmacological activities, among them: wound healing, anti-irritating, hydrating and remover of necrotic tissue, stimulating the cell mitosis; as well as promoter of epithelial stimulation, analgesic action and keratolytic activity,” observe researchers Lorena Ulhôa Araújo and colleagues in a recent article. “For all these reports, allantoin has been used in cosmetic and pharmaceutical preparations for over 70 years with different therapeutic purposes and especially as a wound healing booster.”6

The results of research reported by Araújo and her associates suggests that the wound healing mechanisms induced by allantoin include regulation of the inflammatory response and stimulation of fibroblast proliferation and extracellular matrix synthesis.6 In addition to lowering inflammation, research has shown an ability for allantoin to relieve pain that involves the opioid receptor.7

In addition to healing the skin, allantoin has shown promise against asthma in a mouse model.8 Animals treated with allantoin had lower levels of immunoglobulin E and cytokines that included interleukins 4 and 5 in bronchoalveolar lavage fluid, as well as less inflammatory cell infiltration compared to a control group. The effectiveness of the compound was similar to that of the asthma and allergy drug montelukast.

Blood Sugar and Beyond

In diabetic rats, allantoin dose-dependently decreased plasma glucose.9 Treated animals also experienced an increase in plasma beta-endorphin, a hormone used by the body in the reduction of stress. Allantoin additionally enhanced beta-endorphin release from adrenal glands isolated from diabetic rats. Further investigation demonstrated that allantoin increased glucose uptake in skeletal muscle.

Research has determined that allantoin can activate imidazoline receptors that are also activated by the drug metformin to lower blood sugar. It has been noted that allantoin has a chemical structure similar to metformin.10

In a study involving insulin-producing pancreatic beta cells treated with the diabetes-inducing compound streptozotocin, allantoin limited apoptosis (programmed cell death) and cell toxicity and increased the cells’ viability.11 When injected into streptozotocin-treated rats, allantoin lowered plasma glucose levels. M. Amitani and colleagues concluded that “allantoin and related analogs may be effective in the therapy for beta-cell damage.”

In another study involving rats rendered diabetic by streptozotocin injection, one-month treatment with allantoin lowered glucose, hemoglobin A1c, total cholesterol, low-density lipoprotein (LDL) cholesterol, and malondialdehyde (a marker of lipid peroxidation) compared to animals that received streptozotocin alone.12 Additionally, improvements were observed in levels of the antioxidant enzyme superoxide dismutase, glutathione, and other factors. The administration of crude yam (Dioscorea batatas) powder and a water extract of yam, both of which contain allantoin, were also associated with improvements. Yam peel has also been shown to contain a high amount of allantoin, which may have antioxidant and antitumor effects.13

The Anti-Aging Effects of Allantoin

Allantoin has shown memory-enhancing effects while increasing the proliferation of immature neurons in the hippocampal dentate gyrus region in the brains of mice, which suggested to the scientists involved in the research “that allantoin has therapeutic potential for the cognitive dysfunctions observed in Alzheimer's disease.”14

Allantoin has been recently identified as a mimetic of calorie restriction.15 Caenorhabditis elegans worms that received allantoin lived 20% longer than untreated worms and differently expressed several hundred genes. “We have shown that rapamycin, LY‐294002, TSA and allantoin can increase lifespan in C. elegans in a manner that does not act synergistically with calorie restriction‐induced lifespan extension, indicating that these compounds and calorie restriction may act through a similar mechanism,” write S. Calvert and colleagues. “Additionally, we have shown that this lifespan extension comes with a possible slowing of aging seen through a moderately slower decline in pharyngeal pumping rate, but with no change in movement rate decline.”

They add that allantoin has been found to bind to imidazoline receptors and have beneficial effects on energy regulation, possibly through the activation of AMP kinase which could then act through the mTOR (mechanistic target of rapamycin) pathway.

A subsequent study involving the identification of mimetics of the healthspan-extending drugs metformin and rapamycin via bioinformatic approaches and deep learning methods identified allantoin as a metformin mimetic.16 “The compound exhibiting the highest similarity to metformin according to the metformin classifier was allantoin, a key beneficial compound in yam (Dioscorea spp.),” A. Aliper and colleagues write. “Being a guanidinium derivative, allantoin is similar to metformin in structure and has been shown to induce glucose lowering effects via imidazoline I-2 receptors.” However, more safety data is required to support the use of orally administered allantoin.

While metformin is a prescription drug and allantoin is not available as a supplement, you can obtain some of the plant sources of the compound and find topical products that contain it. Research has determined that allantoin and allantoin complexes are safe at commonly used concentrations.17

References

  1. Gus'kov EP et al. Dokl Biochem Biophys. 2002 Mar-Apr;383:105-7.
  2. Gus'kov EP et al. Dokl Biochem Biophys. 2004 Sep-Oct;398:320-4.
  3. Klouchek-Popova E et al. Acta Physiol Pharmacol Bulg. 1982;8(4):63-7.
  4. Wang XC et al. World J Gastroenterol. 2003 Mar;9(3):568-71.
  5. Campanati A et al. Dermatol Surg. 2010 Sep;36(9):1439-44.
  6. Araújo LU et al. Acta Cir Bras. 2010 Oct;25(5):460-6.
  7. Florentino IF et al. J Ethnopharmacol. 2016 Jun 20;186:298-304.
  8. Lee MY et al. Int Immunopharmacol. 2010 Apr;10(4):474-80.
  9. Niu CS et al. J Agric Food Chem. 2010 Nov 24;58(22):12031-5.
  10. Lin KC et al. Horm Metab Res. 2012 Jan;44(1):41-6.
  11. Amitani M et al. PeerJ. 2015 Aug 6;3:e1105.
  12. Go HK et al. Nutrients. 2015 Oct 15;7(10):8532-44.
  13. Liu Y et al. J Food Sci. 2016 Jun;81(6):H1553-64.
  14. Ahn YJ et al. Food Chem Toxicol. 2014 Feb;64:210-6.
  15. Calvert S et al. Aging Cell. 2016 Apr;15(2):256-66.
  16. Aliper A et al. Aging (Albany NY). 2017 Nov 15;9(11):2245-2268.
  17. Becker LC et al. Int J Toxicol. 2010 May;29(3 Suppl):84S-97S.

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