Introduction:
Several natural interventions are available to provide benefit to patients on chemotherapy. In general, cancer patients on or between chemotherapy regimens should adhere to all healthful dietary and exercise habits as previous to chemotherapy, but follow special guidelines and restrictions as recommended by the oncologist. Some treatments may alleviate fatigue, while others may help with tumor response.
Chemotherapy related fatigue:
Chemotherapy reduces levels of L-carnitine, which is important for energy production in cells, leaving some cancer patients feeling tired. It is a natural compound produced in the body from the amino acid lysine. L-carnitine is required for fatty acid transport and breakdown of fat for energy production.
Cancer patients suffering from chemotherapy related fatigue might benefit from L-carnitine supplementation. Non-anemic (low red blood cell levels that cause weakness) cancer patients (n=50) received oral L-carnitine 4 g/day for a week. Fatigue status was then measured using the Functional Assessment of Cancer Therapy-Fatigue (FACTF) score. After L-carnitine treatment, carnitine levels became normal and the average FACTF score increased from 19.7 at the start of the study to 34.9 after a week of treatment, indicating an improvement in fatigue. These results were maintained until the patients underwent another cycle of chemotherapy. (1)
Chemotherapy reduces levels of L-carnitine, which is important for energy production in cells, leaving some cancer patients feeling tired. According to research daily 2 g of L-carnitine supplementation for a month did not significantly improve fatigue in cancer patients compared to placebo. At the end of the 4-week study, L-carnitine levels had significantly improved. Average daily fatigue, measured using the Brief Fatigue Inventory (BFI, measures severity and impact of fatigue on daily functioning of an individual) improved by -0.96 and -1.11 in the treatment and placebo group, respectively. However, the improvement was not significantly different between the two groups. Additionally, fatigue measured using the Functional Assessment of Chronic Illness Therapy-Fatigue system which looks at health-related quality of life also did not show a difference between the treatment and placebo group. (2)
A study of 12 cancer patients with advance tumors showed that L-carnitine (LC), important for energy production in cells, supplementation significantly improved fatigue in these patients. Participants received an oral daily dose of LC at 6 g/d for 4 weeks. After LC administration, lean body mass and appetite also increased significantly. Additionally, quality of life improved. (3)
A hormone used in conjunction with chemotherapy:
A hormone used in conjunction with chemotherapy may improve remission rates. In a review of 8 randomized (n=761), controlled clinical trials evaluating the benefits of melatonin as an adjuvant (treatment that is given in addition to the primary (initial) treatment.) therapy for cancer patients with solid tumors undergoing chemotherapy or radiation therapy, researchers found that concurrent use of 20 mg of melatonin once daily compared to standard treatment alone, improved the rate of complete or partial remission by nearly 50% (16.5% for standard care alone vs 32.6% for standard care plus melatonin), increased the one-year survival rate (28.4% vs 52.2%) and decreased the risk of the devastating side effects of conventional therapy such as low platelet count, neuropathy, and fatigue by 87%, 81%, and 63% respectively. (4)
Mills, E. et al conducted a meta-analysis of 10 randomized, controlled trials with 643 patients examined melatonin’s effects (alone or as an adjuvant treatment) on patients with various types of cancer who had solid tumors. Supplementation with melatonin reduced the relative risk of death at one year by 34%—regardless of the type of cancer or the melatonin dosage. No adverse effects were reported. (5)
Studies of melatonin suggest that melatonin could improve tumor response to chemotherapy and lower the frequency and severity of chemotherapyrelated side effects (asthenia, thrombocytopenia, stomatitis, cardiotoxicity and neurotoxicity). Two separate studies that included (1) 1440 patients with advance solid tumors receiving supportive care or supportive care plus melatonin (20 mg/day taken at night) and (2) 200 patients with chemo-resistant tumors receiving chemotherapy or chemotherapy plus melatonin (20 mg/day taken at night) were analyzed. Results show significantly lower frequency of cancer related weight loss, lower loss of strength/energy, less thrombocytopenia (low platelet count) and lower rates of lymphocytopenia (low white blood cell count) in patients treated with melatonin than in those who received supportive care alone. (6)
Assessment and Plan: Chemotherapy and Natural Interventions
- In general, cancer patients on or between chemotherapy regimens should adhere to all healthful dietary and exercise habits as previous to chemotherapy, but follow the special guidelines as recommended by the oncologist.
- Cancer patients suffering from chemotherapy related fatigue may benefit from levocarnitine (L-carnitine) supplementation, but an improvement was not seen in all trials. The subjects in research that showed benefit in fatigue used a dose of 4-6 grams per day divided into 3 doses taken for 1-4 weeks while on chemotherapy (1,2,3).
- L-carnitine should not be taken without approval from a physician overseeing care. Adverse effects include halitosis (7), diarrhea, and rash which have been reported with higher doses. L-acetylcarnitine has been reported to induce seizures (9) and at the same time prevented seizures by lowering ammonia levels and reducing neurotoxicity (8). L-carnitine levels may be depleted by some anti-convulsants and cause an increase ammonia blood levels sometimes resulting in encephalopathy (11). Supplementation by L-carnitine is able reduce this elevated ammonia level (10). It may also make hypothyroidism worse by reducing the absorption of thyroid hormone.
- The most common dose of melatonin used was an oral dose of 20 mg once daily taken at night. Compared to standard treatment alone, melatonin improved the rate of complete or partial remission in cancer patients with solid tumors undergoing chemotherapy or radiation therapy (4). Melatonin improved the survival rate at one year, and it lowered the risk of low platelet count, neuropathy, and fatigue (4,6). Supplementation with melatonin reduced the relative risk of death at one year without adverse effects (5). Melatonin lowered the rate of chemotherapy related fatigue, oral toxicity, cardiac adverse effects and neurotoxic complications (6).
References:
1.Graziano F, Bisonni R, Catalano V, et al. Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anemic cancer patients. Br J Cancer. 2002 Jun 17;86(12):1854-7. http://www.ncbi.nlm.nih.gov/pubmed/12085175
2.Cruciani RA, Zhang JJ, Manola J, et al. L-carnitine supplementation for the management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2012 Nov 1;30(31):3864-9. http://www.ncbi.nlm.nih.gov/pubmed/22987089
3.Gramignano G, Lusso MR, Madeddu C, et al. Efficacy of l-carnitine administration on fatigue, nutritional status, oxidative stress, and related quality of life in 12 advanced cancer patients undergoing anticancer therapy. Nutrition 2006 Feb;22(2):136-145. http://www.ncbi.nlm.nih.gov/pubmed/16459226
4.Wang YM, Jin BZ, Ai F, et al. The efficacy and safety of melatonin in concurrent chemotherapy or radiotherapy for solid tumors: a meta-analysis of randomized controlled trials. Cancer Chemother Pharmacol. 2012 May;69(5):1213-1220. http://www.ncbi.nlm.nih.gov/pubmed/22271210
5.Mills E, Wu P, Seely D, Guyatt G. Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res. 2005 Nov;39(4):360-6. http://www.ncbi.nlm.nih.gov/pubmed/16207291
6.Lissoni P. Is there a role for melatonin in supportive care? Support Care Cancer. 2002;10:110-116. http://www.ncbi.nlm.nih.gov/pubmed/11862501
7.Rocher F, Caruba C, Broly F, Lebrun C. ev Neurol (Paris). L-carnitine treatment and fish odor syndrome: an unwaited adverse effect. Article in French. 2011 Jun-Jul;167(6-7):541-4. http://www.ncbi.nlm.nih.gov/pubmed/21481905
8.Matsuoka M, Igisu H. Comparison of the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia. Biochem Pharmacol. 1993 Jul 6;46(1):159-64. http://www.ncbi.nlm.nih.gov/pubmed/8347126
9.Fariello RG, Zeeman E, Golden GT, Reyes PT, Ramacci T. Transient seizure activity induced by acetylcarnitine. Neuropharmacology. 1984 May;23(5):585-7. http://www.ncbi.nlm.nih.gov/pubmed/6738826
10.Mock CM, Schwetschenau KH. Levocarnitine for valproic-acid-induced hyperammonemic encephalopathy. Am J Health Syst Pharm. 2012 Jan 1;69(1):35-9. http://www.ncbi.nlm.nih.gov/pubmed/22180549
11.Hiraoka A, Arato T, Tominaga I. Reduction in blood free carnitine levels in association with changes in sodium valproate (VPA) disposition in epileptic patients treated with VPA and other anti-epileptic drugs. Biol Pharm Bull. 1997 Jan;20(1):91-3. http://www.ncbi.nlm.nih.gov/pubmed/9013816