Arginine, Immune Function & Cancer
This article first appeared in the
April, 1994
issue of VRP's Nutritional News
by A.S. Gissen
Research Brief
During the past 15 years numerous studies utilizing both animal and human
subjects have shown that dietary supplementation with L-arginine can
stimulate immune functions and host defenses. L-arginine
has also demonstrated the ability to inhibit the growth of tumors in
transplanted and chemically-induced animal tumors. Enhancement of host defense
mechanisms is believed to play a significant role in L-arginine's anticancer
properties.
A study examining the effect of L-arginine supplementation on immune function
in patients with breast cancer was recently published. This study examined
the effect of dietary supplementation with 10 grams of L-arginine, three
times daily, for three days on host defenses in patients with breast cancer.
The authors of this study had previously demonstrated that L-arginine
significantly increases natural killer (NK) and lymphokine- activated killer
cell cytotoxicity (LAK) in health volunteers after L-arginine administration,
and this newer study was the first to examine the effect of L-arginine in
patients with previously untreated cancer.
L-arginine was found to significantly enhance several measures of immune
function. The mitogenic responses of peripheral blood lymphocytes were
increased approximately 60 percent, while NK and LAK cytotoxicity were
increased by 81 and 107 percent respectively. Interestingly, this enhancement
of host defenses was not accompanied by increases in serum levels of
cytokines, including interleukin-1 and 2, gamma-interferon, and tumor
necrosis factor. The authors commented that immune biologic modifiers in
current clinical use, in particular gamma-interferon and interleukin-2, have
achieved limited clinical success due to their considerable expense and
treatment-related toxicity. L-arginine was able to significantly enhance
natural cytotoxicity without side-effects and at low cost.
Unfortunately, how L-arginine is able to enhance immune functions is unclear.
Because L-arginine is able to stimulate host defenses in well nourished and
healthy individuals, it is unlikely that supplementation overcomes an
L-arginine deficiency. L-arginine has been shown to stimulate hormone
secretion, particularly growth hormone. Growth hormone has demonstrated
numerous biological effects that may account for the properties of
L-arginine, including wound healing and immunostimulation. The authors point
out, however, that L-arginine has resulted in similar immune activation when
added to cell cultures in vitro, thus negating the possible role of growth
hormone. Based on the recent discoveries of the wide biological functions of
nitric oxide, for which L-arginine is a precursor in the body, it seems
plausible that enhanced nitric oxide production may represent part of
L-arginine's mechanism of action.
This paper concludes with a discussion of the research showing that apart
from its ability to substantially enhance anticancer defenses, L-arginine can
also increase the rate of tumor protein synthesis in patients with cancer.
The authors stated that, "Although this may represent stimulation of
tumor growth by L-arginine, these properties can be used effectively to sensitize
the tumors in patients with breast cancer to neoadjuvant chemotherapy."
They commented that other researchers have shown that many nutrients can
stimulate tumor growth, and this can be exploited to potentiate the tumor
response to chemotherapy. This is because many chemotherapeutic agents are
cell-cycle specific, killing only cells that are dividing and having little
effect on resting tumor cells. The authors conclude that because it has been
demonstrated that the response of cancer to chemotherapeutic agents is
correlated with the number of cells that are actively dividing, and
chemotherapeutic regimens have been shown to suppress natural cytotoxicity
for up to 6 months following completion of treatment, L-arginine
supplementation may, "both potentiate the response of tumor cells to
anti-cancer cell drugs in chemotherapy and reduce the immunosuppressive
effects of chemotherapeutic agents."
Taken as a whole, the growing amount of research into L-arginine's possible
roles in clinical medicine has not translated into clinical practice. L-arginine
is inexpensive, readily available, and apparently effective. It has been used
successfully to stimulate wound healing and immune function by a small group
of dedicated researchers and clinicians. It appears, however, that as a
natural and unpatentable substance L-arginine faces an almost insurmountable
barrier to gaining clinical acceptance. While the work of researchers will
hopefully elucidate L-arginine's mechanism of action as an immunomodulator in
the coming years, it is doubtful that L-arginine will join the arsenal of
cancer chemotherapy anytime soon.
Reference:
J. Brittenden, K.G.M. Park, S.D. Heys, et al, Surgery 1994, 115: 205-212.