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peripheral nervous system cells. They are thought to have acids could reduce the oxidative stress and inflammation
57
many beneficial effects in neurodegenerative diseases. They induced by chemotherapy and could have neuroprotective
can also regulate signal transduction by their effect on ion effects. However, some of the nutrients, such as vitamin B
channels and receptor functions and decrease the production complex, have not been found to provide any significant
58
of proinflammatory cytokines related to neuropathy. 57,58 At improvements in CIPN. A previous review by Schloss et al
73
present, only 1 RCT has aimed to examine the effects on suggested that single ingredient vitamins, such as pyridoxine
CIPN, and the results showed that omega-3 fatty acids were (vitamin B ), have stronger evidence for oxaliplatin-induced
6
an efficient neuroprotective agent for prophylaxis against PN (level 2) and should be researched separately.The evidence

paclitaxel-induced peripheral neuropathy in patients with in support of ALC, α-LA, GSH, and Ca /Mg is still
2+
2
breast cancer. Another clinical trial compared the effects of insufficient, and that of ALC for taxane-based therapy in
59
omega-3 fatty acids and vitamin E on the incidence of breast cancer seems to be especially discouraging. Thus, this
peripheral neuropathy in patients receiving taxol, and the study suggests that not all of the nutrition supplements have
data suggested that omega-3 fatty acids may significantly anti-neurotoxic properties.
reduce the incidence of paclitaxel induced-peripheral The complete mechanisms of nutrients in managing
neuropathy (PN). 60 CIPN are not known. Many in vivo studies have claimed that
the respective nutrients exhibited significant neuroprotective
Calcium and Magnesium activity in rat and mice models. However, the subsequent
Calcium (Ca ) and magnesium (Ma ) are essential clinical studies were insufficient to prove the findings of the
2+
2+
cations that play a crucial role in many physiological in vivo studies. Detailed RCTs are necessary to confirm the
functions. For instance, Ca and Mg are involved in bioactivity of nutrients, because they could aid in the
2+
2+
energy-requiring metabolic processes, protein synthesis, development and marketing of nutrient-based complementary
membrane integrity, nervous tissue conduction, therapies for the management or prevention of CIPN. In
neuromuscular excitability, enzymatic systems and hormone addition to the nutrients we have discussed, several herbal
secretion. 61,62 In addition, Ca and Mg are hypothesized to preparations have been recognized to have anti-inflammatory
2+
2+
decrease oxaliplatin-induced hyperexcitability, which is activity and are also suggested to have anti-CIPN properties.
thought to involve the reconfiguration of sodium channels in Several phytochemicals and Chinese herbal formulas have
the cell membrane that cause CIPN. 63-65 One study showed been identified as having the ability to prevent free radical
that hypomagnesaemia is associated with oxaliplatin-induced damage. In addition to their antioxidant capabilities, they
74
neuropathy in colorectal cancer patients. 66 have been shown to have neuron stabilizing properties,
At present, only 1 study has compared the efficacy decreasing the stimulants of sensory disturbance and pain.
74
between dietary intake of Ca and Mg for preventing CIPN However, a need exists for the identification and prediction
2+
2+
in patients with colorectal cancer, and the results showed that of potential herb–drug or nutrient–drug interactions. 75,76
Mg was significantly associated with lower prevalence of
2+
CIPN, whereas Ca and Mg was not. However, the CONCLUSION
67
2+
2+
efficacies of Ca and Mg infusions are still inconclusive. An adequate supply of nutrients is essential to well-being
2+
2+
Some studies have found a lower occurrence and severity of and may provide the opportunity for nerve regeneration and
CIPN with intravenous Ca and Mg infusions. 68,69 On the function after chemotherapy toxicity, and also with regard to
2+
2+
other hand, some studies have not found significant protective the effects of other current Western medical treatments.
effects of intravenous Ca and Mg infusions on sensory Therefore, basic evidence-based nutritional knowledge is
2+
2+
scale of life questionnaires. 70,71 essential for clinical physicians and their medical teams.
Complementary interventions such as dietitian consultation
DISCUSSION could be used as promising, cost-effective, and practical
Despite the high incidence of CIPN and its dose-limiting methods for patients with CIPN. Nutritional interventions
effects, no standard treatments or preventive options with should be integrated as an important pillar in the
recommended efficacy and safety data are available. The multifactorial, biopsychosocial treatment of our CIPN
8
complexity involved in the effects of chemotherapy on the patients. Moreover, future studies exploring the efficacy of
nervous system has hindered a unified understanding of the nutrients on CIPN onset and/or evolution should be strongly
specific mechanisms underlying this condition. The lack of encouraged to move toward a holistic approach to the
72
effective therapeutic methods for CIPN has boosted the need prevention and management of CIPN.
for the use of nutrients. Thus, nutrients have gained increasing
attention for patients because they are convenient, ACKNOWLEDGEMENTS
economical, safe, and possibly therapeutic. This study was funded by Chang Gung Memorial Hospital (CMRPG-8I0381), and
So far, the findings in our report and the pertinent supported by the Taiwan Ministry of Health and Welfare (MOHW106-CMAP-M-114-112107
& MOHW107-CMAP-M-114-122111). We thank all our colleagues from the Cancer
literature have suggested that nutrient supplementation has Center and CM ward of Kaohsiung Chang Gung Memorial Hospital for their enthusiastic
potential protective benefits for CIPN. Some of the studies, help in this work. We also thank Miss Hsiang-Yu Wang, Department of Visual
Communication Design, Shu-Te University, for drawing the figures. Yan-Wen Liu and
for example, have found that glutamine and omega-3 fatty Chun-Ting Liu contributed equally to this work and should be considered co-first authors
Liu—Complementary Nutritional Supplements and Chemotherapy-induced ALTERNATIVE THERAPIES, JUL/AUG 2020 VOL. 26 NO. 4 47