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Prepared
by: Dr. Charlene DeHaven, Clinical Director
SAFETY OF KOJIC ACID
Kojic acid is commonly used for dermal pigmentary
problems and an exhaustive review of the medical literature
illustrates its safety in this regard. In addition to its safety as
a lightening agent, it possesses several other characteristics
beneficial to skin health. These are well-described in scien-
tific studies and include cancer-fighting effects, protection
against photoaging, and excellent antioxidant effects.
WHERE FOUND
Kojic acid is commonly found in cosmetic products where it
is used for its effect on melanocytes in lightening pigment
and as a food additive to retard spoilage. Its natural source
is from various fungi, including Aspergillus and Penicillium.
It is found in association with several grains, particularly
soybeans and soybean products. It was first identified over
100 years ago as a component of sake (rice wine).
CURRENT INTERNATIONAL COSMETIC MILIEU
United States — The US government has
issued no bans or warnings on the use of kojic acid in
foods and/or cosmetic products. It is commonly found as
a food additive in the US because of its antioxidant (spoilage-preventing)
effects and flavor-enhancing effects. It is also found
in cosmetic prepa- rations. It is found in soy products,
including soybean paste, soy sauce and rice wine (sake).
Kojic acid would be virtually impossible to remove from
these common foods because it is produced by several species
of fungi found with soybeans and other grains.
Japan — Although prior
medical literature in Japan and also world-wide found
no carcinogenic potential with kojic acid, a 1999 study
showed that kojic acid at very high doses given orally
to rodents caused some stimulation of thyroid cells by
increasing TSH. This study showed no carcino- genic (cancer-causing)
potential but was extrapolated to this ONLY THEORETICAL
POSSIBILITY. Another study, also using extremely high
oral doses of kojic acid also in rodents, showed a slight
increase in stimulating liver cells to develop adenomas
(benign, NOT malignant, tumors). A suggestion was also
made that there COULD be genetic toxicity, since liver
adenomas were increased. No associa- tion was found with
the development of malignant tumors (cancers) in these
studies. The Japanese government has stated there is no
immediately safety concern, but has ordered further studies
be done with kojic acid. These future studies have been
outlined by Japan’s Ministry of Health and Welfare and
include DNA composition with kojic acid stimulation, tumor
initiation and promotion studies in rats, and endodermic
absorption studies in humans. Japan is allowing all present
products containing kojic acid to be sold from shelves
but has ordered the importation of foreign cosmetics containing
kojic acid to stop until results of the additional studies
are complete. Kojic acid is commonly found cosmetic ingredient
in Japan because it is used for skin lightening in a population
having more melanin and considering pale skin to be desirable.
Kojic acid has been used in Japan and the rest of Asia since
1988 with no reports of any problem. In Asia, it has always
been a constituent of soy products in foods, including miso
(soybean paste), soy sauce and sake. In fact, it has been
consumed avidly in the diet for generations for its supposed
health benefits. In spite of this large oral consumption, no
problems have been reported with its use in the past.
Korea — The Korean government, like Japan,
states there is no presently known danger from kojic acid
and continues to allow products containing kojic acid
to be sold. Also like Japan, Korea has banned the importation
of products containing kojic acid from foreign manufacturers
pending results of the future Japanese testing. The Korean
Cosmetic Industry Association notes that 30% of all cosmetic
formulations sold in Korea contain kojic acid. It is a
popular ingredient for skin lightening in this population
having more melanin in their skin.
Switzerland — Switzerland has banned
kojic acid from products sold in their country because
of the results of the recent Japanese studies on thyroid
and liver cells in rodents.
MEDICAL STUDIES—POSITIVE AND NEGATIVE-
DONE IN ANIMALS OR IN THE TEST TUBE
An exhaustive review of the worldwide scientific literature
was done. No studies done in humans show any tumor-
promoting effect of kojic acid or any significant toxicity even
above the usual topical or oral dose. And numerous studies
illustrate the beneficial effects of kojic acid as an antioxi-
dant, in preventing cancer, in protecting the skin from photo-
aging, in preventing wrinkles, and in enhancing immune
function. The only negative studies found were in very high
doses given to animals in their diet or in laboratory assays
done at high doses in the test tube. Only a small number of
these studies can be found in the scientific literature.
As with most substances, if given in truly huge doses, a
toxic effect can be elicited. For example, if injected intrave-
nously in extremely high doses, seizures can be precipi-
tated. Some recent studies from Japan do show that if
given in extremely high doses in the diet of rodents, a slight
inhibitory effect on thyroid hormone synthesis occurs,
leading to a concomitant small increase in TSH.
This increased TSH translates into mild thyroid gland
stimulation, which can increase the tendency for benign
formation. No tendency towards malignant transformation
was detected; therefore, it is not surprising that no genetic
alteration or toxicity was demonstrated. Other studies of
thyroid cells in rodents did not confirm these results. Also
from Japan are a few studies of rodents which show some
hyperplasia (increased number of normal cells) of liver cells
in rodents given very large amounts of dietary kojic acid.
Other studies involving liver cells do not confirm this effect,
so these results are also conflicting. Both a massive dose of
kojic acid and a long oral administration period were required
to see any effect on either thyroid or liver cells in rodents.
Because kojic acid is contained within various grains fed to
poultry, research was done years ago in the US to determine
the amount required in the diet to cause a potential problem.
The amounts required (2 grams of kojic acid per kilogram of
poultry food) were so large that it was concluded impossible
for this substance to be of concern.
Kojic acid has been found to have other topical benefits in
addition to its effect on melanocytes. It helps prevent skin
wrinkling due to photodamage via antioxidant and metal-
chelating effects. It has a very prominent antioxidant effect
in quenching singlet oxygen and other free radicals.
In spite of the few studies suggesting a link with benign
neoplasms, many more studies have shown the cancer-
preventive effects of kojic acid. When placed with sulfur
mustard (a very potent cancer-causing agent) in skin cell
culture, kojic acid reduced the sensitivity to the neoplastic
agent and helped prevent the development of malignant
cells lines. Kojic acid has been suggested as a potentiator
for other cancer treatments because of its antifungal effects
and effects against leukemias and other cancers. It also
increases the natural function of the body’s own cellular
immunity. Its positive effects on host immunity relate to both
a direct effect on cellular immune function and a free
radical-quenching effect on the chemical byproducts created
by normal immune functioning that could damage adjacent
healthy tissues if not neutralized.
SUMMARY
Over a period of many years, numerous studies are found in
the scientific literature which shows that kojic acid actually
has potential as a treatment for cancer, to decrease
tendency towards malignancy, and that it is an excellent
antioxidant, providing numerous benefits on that basis also.
Kojic acid has been found in the Asian diet for many genera-
tions and, in fact, has been consumed avidly for supposed
health benefits. It is found in soybeans and all soybean
products. Considering its wide consumption for such a long
period, it seems extremely unlikely there are any negative
effects to oral consumption and certainly not for topical use.
Epidemiologic studies involving humans have shown no
link to cancer or any other adverse medical condition. Also
of interest is the fact that, although now under an import
ban for cosmetics, kojic acid is so universally found in
soybeans, soybean products and sake that it would be
impossible to remove it from the Asian diet.
The recent studies that generated concern were done in
Japan using rodents. They have been criticized because
their results were conflicting and the doses of kojic
acid used were massive and given orally over a long period
of time. They did show a minor stimulation effect on thyroid
cells via TSH increases in a small percentage of animals,
but some studies found this translated into slightly more
benign tumors in the kojic acid group while other studies
did not confirm this. A few studies were done involving
liver cells in rodents and, once again, were conflicting,
with some showing a minor increase in the growth of normal
cell types and some not. There was no increase in the
occur - rence of malignancies. No genetic toxicity to
thyroid or liver cells or any other cell type was demonstrated.
Overall, kojic acid seems to be safe when consumed in
foods and also when used topically in cosmetics. It also
has benefits as an antioxidant, in preventing photoaging,
and in protecting against malignant transformation.
 References
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while Potentiating Leukocyte Functions including Free
Radical Generation”,
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