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Abstract
This article reviews updates and provides some data related to nutritional and orthomolecular supplementation in oncology
patients with an emphasis on lung cancer, a commonly diagnosed tumor with significant nutritional disturbances. Cancer
and its treatment play a significant role in nutritional imbalance which likely has negative impact on the patient both in terms
of quality and quantity of life. Nutritional supplementation may correct these imbalances with significant clinical benefit both
physiologically and psychologically.This review will help assist in providing clinically useful data to assess the cancer patients
nutritional status and to guide nutritional intervention to assist these patients recovery.
Keywords
orthomolecular, supplementation, nutrition, lung cancer, questionnaire
Introduction
At least one third of all cancers may be influenced by
nutrition.1 Dietary intake effects metabolism, which in turn
affects both physiological and psychological homeostasis.
Furthermore, response to cancer treatment may also be influenced by adequate intake of nutritional components, both in
terms of healing from therapy and recovery from the cancer
itself.
For many patients, cancer leads to great difficulties in
achieving a nutritionally appropriate diet. The tumor may
secrete myriad factors that interfere with eating or absorption. Appetite, taste, smell, and the ability to consume,
digest, and absorb food are affected. In addition, treatment
for cancer may lead to the same outcomes. For example,
chemotherapy is generally associated with loss of appetite,
diminished taste, nausea, and weakness among other morbidities. Radiation therapy also may promote a generalized
weakness and malaise, and radiation treatment portals generate specific side effects such as mucositis or enteritis, each
with a negative effect on nutrition intake and absorption.2
Surgery may promote significant imbalances in nutrition as
wound healing requires great caloric intake, sometimes
beyond the capacity of the individual with cancer.
This nutritionally compromised state will then further
diminish the patients immune system, ability to heal, fight
infection, and maintain an acceptable quality of life. These
nutritional compromises are pronounced in lung cancer.
This review will provide an update of peer-reviewed scientific data related to the impact and outcome of
orthomolecular nutritional supplements, with an emphasis
on lung cancer patients.
Background
Oxidative Stress and Disease
A free radical is an atom or molecule that has at least 1
unpaired electron and is therefore unstable and highly reactive. Free radicals are generated during cancer treatment
and are responsible for cellular damage and killing malignant cells. Oxygen radicals are also generated in the
human body by a variety of mechanisms and exposures,
including thermolysis; photolysis; redox reactions; the Fenton
reaction; ionizing radiation; sun light; chemical toxins (carbon
tetrachloride, paraquat, benzo, pyrene), aniline dyes, and toluene;
chemotherapeutic
1
The Brody School of Medicine, East Carolina University, Greenville, NC,
USA
2
Clinice, Rio de Janeiro, Brazil
Corresponding Author:
Carlos Austerlitz, East Carolina University, 600 Moye Blvd, Greenville, NC
27834, USA
Email:camposc@ecu.edu
399
Campos et al
O2 (100%)
Mitochondrial
H2O2 (95-98%)
2-5%
O2+ e
Superoxide dismutase
(Cu, Zn, Mn)
Yes
Terminate
No
Endogenous
defense
H2O2
Glutathione
redutcase (B2)
Cell
Catalase (Fe), Glutathione
peroxidase (Se)
Ionizing
radiation
Terminate
Yes
No
Haber
Weiss
Fenton
OH*
Fatty acid
No endogenous
defense
Figure 1. Oxidation pathways within the human body for oxygen metabolism and ionizing radiation
400
401
Campos et al
Table 1. Free Radicals, Antioxidant Defense Network
Antioxidant
Free Radical
Exogenous
(O2-)
Superoxide anions
Hydrogen peroxide (H2O2)
Hydroxyl (OH-)
Oxygen, singlet (O2)
Lipidic peroxide (COOH-)
Endogenous
Superoxide dismutase (Mn, Zn, Cu)
Catalase (Fe), glutathione peroxidase
(Se), glutathione reductase (Vitamin
B2), melatonin
Melatonin39
Melatonin39
402
Orthomolecular Supplementation
Many lung cancer survivors have low blood nutrient levels
even before diagnosis as a result of inadequate diets and/or
the adverse effects of smoking.40 For example, the Food and
Nutrition Board of the National Academy of Sciences recommends that individuals who smoke consume an additional
35 mg of vitamin C per day.
Mahdavi et al7 have determined the levels of oxidative
stress, serum total antioxidants, and vitamin C in a cohort of
57 cancer patients and 22 healthy participants. The level of
oxidative stress was measured by malondialdehyde (end
product of lipid peroxidation). Cancer patients as compared
with controls, showed a significant increase in lipid peroxidation with a concomitant decrease in the antioxidant
defense system. In addition, low serum levels of vitamin C
in spite of adequate daily intake may be because of increased
use in scavenging lipid peroxides as well as their sequestration by tumor cells.
Levels of oxidative stress in patients with lung cancer
have also been measured by Esme and coauthors.41 In this
study, a cohort of 49 lung cancer patients, who had not
received any cancer therapy, and 20 healthy participants
were evaluated. Serum nitrite, nitrate, ascorbic acid, retinol,
b-carotene and ceruloplasmin levels, and whole-blood
malondialdehyde, reduced glutathione levels, and catalase
activity were measured. Statistically significant differences
between the patient group and the control group were
detected for all biochemical parameters. It was advocated
that with advancing stage of lung cancer, the levels of oxidative stress increase, and levels of antioxidant molecules
decrease. Patients with squamous cell carcinoma had higher
403
Campos et al
Another study involving small-cell lung cancer patients and
effects of vitamin intake and folate status on disease-free survival has been performed by Jatoi et al.50 In this study,
supplemental vitamin usage, dietary vitamin intake (Willett
Food Frequency Questionnaire), red blood cell folate, and
serum folate concentrations were assessed. In this cohort of
patients, it was concluded that those who took vitamin supplements were more likely to be long-term survivors (41 months
vs 11 months; P = .002). A similar trend toward long-term survival was seen among patients with higher circulating folate
concentrations.
The effect of chemotherapy alone versus chemotherapy
plus a high dose of multiple antioxidants in patients with
advanced NSCLC have been published by Pathak and collaborators.51 In this study, 136 patients with stage IIIB to IV
NSCLC were randomized to receive chemotherapy (paclitaxel and carboplatin) alone (chemotherapy arm, n = 72) or
chemotherapy in combination with ascorbic acid 6100
mg/d, dl-a-tocopherol (vitamin E) 1050 mg/d, and b-carotene 60 mg/d (combination arm, n = 64). It was reported
that antioxidant supplementation during paclitaxel/carboplatin-containing chemotherapy in NSCLC appears to be safe
and does not compromise the efficacy of standard chemotherapy.
Although all these results indicate a potential benefit for
supplementation, large-scale randomized trials will be
required before supplementation is accepted as a standard
of care in this patient population.
404
Table 2. Antioxidant and Micronutrients to Help Prevent and Mitigate Treatment-Related Toxicities in Lung Cancer Patients
Action: Supplementationa
Action: Supplementationa
Allergies:Vit. C, methionine
Anemia: iron, folic acid,Vit. B12,Vit. C,Vit. E, Se, L-glutamine, lactobacillus
Anxiety: L-5-hydroxytryptophan, L-taurine, B-complex
Antiherpes: lysine, Zn,Vit C
Anti-inflammatory: carnosine, omega-3, omega-6
Antimyelodysplastic: melatonin
Antiangiogenic:Vit. E
Appetite:Vit. B1
Bleeding gums: bioflavonoids,Vit. C
Blood: pressureVit. E,Vit. B3. Ca, Cr, arginine, PH (K); circulation
Vit. B3, Gingko biloba; clottingCa; vessel permeabilitybioflavonoids; red cell formationVit. B12, Folic acid; coagulationVit. K
Bone marrow toxicity: melatonin
Cisplatin toxicity: glutathione
Dehydration: K
Cholesterol breakdown: Mn, methionine,Vit. A
Circulatory system: biotin,Vit. E
Collagen: bioflavonoids
Detoxification: glutathione, silymarin
Digestive system:Vit. B3, L-glutamine, lactobacillus, digestive enzymes
Fatigue:Vit. E, iron,Vit. C, B-complex
Glycosylation: inhibitionmelatonin; protectionV, carnosine
Glucose metabolism:V, Cr
Hair loss:Vit. E, methionine, biotin,Vit. B2
Heart: N-acetylcysteine,Vit. E,Vit C
Hemoglobin formation: iron,Vit. C
Hepatic detoxification: cysteine, methionine, silymarin
Hypertension: coenzyme Q-10, Mg, omega-3
Insomnia: melatonin, l-taurine, inositol, Ca, Mg, L-5-hydroxytryptophan
Immune boosting: carnosine, melatonin, lactobacilus, lycopene
Lung:Vit. A, cysteine
Muscle:Vit. B1; growthL-carnitine; painbiotin; metabolism
arginine; functionCa, K
Neuropathy: K, Ca, Mg, a-lipoic acid,Vit. B6, glutathione
Nervous system:Vit. B3,Vit. D,Vit. B1
Oxidative stress:Vit. C, Zn, Mn, Se,Vit B2, glutathione, Cu
Periodontal disease: coenzyme Q-10,Vit. C
Prostaglandin synthesis: Glutathione
Protein synthesis: Zn, Glutathione
Tissue regeneration: folic acid,Vit. A,Vit. B2,Vit. B3, biotin, K,
methionine, erythema (grape seed oil, external use)
Wound healing: Se; regenerationVit. C, Cu, Zn
Yeast infection: Lactobacillus, Zn
Abbreviation:Vit., vitamin.
a
Chelated metal should be used to improve absorption.
Physical activity
Supplementation
(tailoring to the
individual)
Breakfast: whole grains cereal with yogurt, whole grain bread with cream To increase calories and gain weight,
cheese, or cooked cage free eggs. Green tea or coffee with whole milk
decrease glycemic index, mitigate
Morning snacks: natural blended fruit juice (apple, plums, peaches, banana,
inflammation (foods rich in omega-3
pear) with honey and nuts (eg, walnuts and macadamia)
fatty), facilitate swallowing and
Lunch: fish and vegetable souffl or sweet mashed potatoes with cooked
stimulate the immune system
chicken breast. Spinach cream with soy meat
Afternoon Snacks: Soft peanut cookie, pudding with fruit jelly or milkshake
Dinner: vegetable soup made with fish/chicken/soy broth; whole rice and
vegetable souffl
Night Snacks:Yogurt or dark chocolate pudding
Remark: Whatever it is possible, include in the meal nutraceutical foods
(rosemary, soybean, shiitake mushroom, mung bean, garlic, lentil bean,
leek, pomegranate, onion, American ginseng, angelica root, licorice,
dandelion root, ginger, extra virgin olive oil, sesame seed, tomatoes,
nuts, and parsley)
Walk, stretch and respiratory exercise.
To increase appetite, reduce constipaPassive movement or physiotherapy for bed confined patients
tion, prevent muscular weakness,
and counteract fatigue
L-glutamine, Zn and lactobacillus
Stimulate gut absorption and decrease
yeast infection
Melatonin, L-taurine, L-5-hydroxytryptophan, L-taurina, B-complex
Insomnia and anxiety
Coenzyme Q-10 and Vit. C
Periodontal disease
Mitigate nutritional deficiencies
Vit. E, omega-3, Ca, Mg, Cr, Cu, Zn,Vn, B vitamins,Vit. A, a-lipoic acid,Vit.
D3, glutathione, carnosine and beta-carotene
Abbreviation:Vit.Vitamin.
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Campos et al
(WBC, RBC, HgB, Hct, MCV, MCH, MCHC, RDW,
platelet count), serum chemistries (Na, K, Cl, CO2, Ca,
glucose, BUN, total protein, Alb, T bili, ALK phosphatase,
SGOT, SGPT, Cr, anion gap, uric acid), lipid panel (cholesterol, HDL, LDL, triglyceride), and others (vitamin
B12, ferritin, folate, HbA1C, c-reactive protein [CRP], and
homocysteine).
The nutritional questionnaire included patient data
(name, sex, date of birth, present weight, usual body weight
and height); supplement intake (b-carotene, thiamin, riboflavin, niacinamide, vitamin B6, cobalamin, amygdaline,
biotin, folic acid, ascorbic acid calciferol, cholecalciferol,
tocopherol menadione, phylloquinone); minerals intake
(magnesium, iron, calcium, zinc, manganese, chromium,
potassium, copper, selenium, and vanadium); amino acid
intake (lysine, carnosine, cysteine, arginine, methionine,
glutamine l-carnitine); lactobacillus (acidophilus, bulgaricus, rhamnosus); others (coenzyme Q-10, omega 3, omega
6, resveratrol, gingko biloba, bioflavonoids, glutathione,
and melatonin); food allergies/aversion; intake barriers
(depression, dental problems, difficulty chewing, pain,
reflux, nausea, vomiting, diarrhea, constipation, altered
sense of smell and taste, dysphasia); alcohol use; medication use; gastrointestinal problems; domestic and/or
economic difficulties, kind of meal, and frequency (breakfast, morning and afternoon snacks, lunch/dinner and night
snacks); and drugs intake.
The study was performed in the radiation oncology
department of East Carolina University with a cohort of 10
NSLC patients (ages 40-86) randomly selected during a
period of time of 6 months. The results show increased
levels of PTEs identified in this cohort (Pt, As, Sn, Cd, Sb,
Pb, and Al). High total toxic representation was identified in
20%, and very high total toxic representation was found
in 30% of patients. An imbalance for all EEs was identified
in 100% of patients. Abnormal ferritin levels were found in
50% of patients, as also abnormal levels of homocysteine
(70%), HbA1C (50%), ultrasensitive CRP (US-CRP) (60%),
and amino acids (60%). None of the patients met the minimum daily required intake of fruits and vegetables on the
nutritional questionnaire. The presence of PTE and imbalance of EEs can lead to a disruption of protein synthesis,
catabolism, neurotoxicity, myopathy, hemolytic anemia,
renal failure, inflammatory processes, and disruption of
ability to produce antioxidant enzymes. High levels of
homocysteine, HbA1C, and US-CRP may lead to inflammation, increased probability of clot formation, proliferation of
tumor cells, oxidative stress, and aggravated immunological response. From these data, we concluded that all patients
showed evidence of nutritional imbalance, presence of toxic
elements, and imbalance of EEs, which could lead to
increased oxidative stress. Clinical correlation of these
levels prior to, during, and after oncological therapy may
assist in designing a rational intervention, which may
include nutritional intervention, chelation of potential toxic
elements, and mineral and vitamin supplementation to
Conclusions
Enzymes, minerals, and vitamins play an important role in
oxidative stress control. Vitamins in combination with other
nutrients promote normal metabolism and interact with each
other to facilitate absorption within the body Most lung
cancer patients die with nutritional imbalances that are difficult to correct by dietary intake alone. A nutrition questionnaire
together with specific laboratory panels can be implemented
for lung cancer patients. These tools may serve in providing
data to assess the patients nutrition oxidative stress and clinical status, and directing nutrition intervention to
treatment-related complications. This may result in improved
quality of life, decreased morbidity, and prolonged survival.
Declaration of Conflicting Interests
The authors declared no conflicts of interest with respect to the
authorship and/or publication of this article.
Funding
The authors received no financial support for the research and/or
authorship of this article.
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Author Bios:
Diana Campos MD, Federal University of Pernambuco, Brazil.
Physician specialized in Radiation Pathology (REAC/TS, Oak Ridge,
USA), Homeopathy (Brazilian Hahnemanniano Institute) and
Orthomolecular Medicine (Center of Orthomolecular Medicine of
Rio de Janeiro, Brazil). Physician from the Brazilian Nuclear Energy
Commison (1980-2006). Founder and Director of the Orthomolecular
Study Center, Recife, Brazil (2005-currently). Visiting Professor,
Department of Radiation Oncology and Photodynamic Therapy, East
Carolina University (2006-currently) Has published 6 scholarly scientific papers in peer-reviewed journals, authored 2 books
(Homeopathy in HIV Patients and Treatment of overexposure to
Ionizing Radiation), 26 scientific presentations in congresses and
other peer reviewed meetings., and has made numerous invited presentations about medical subjects of public interest in Brazilian
broadcast (radio, newspaper and TV). At her private Clinical in
Recife, Brazil, she provides consultation for about 900 patients yearly.
C Austerlitz Ph.D. degree in nuclear engineering from the Georgia
Institute of Technology (1990). M.S degree in health physics (GaTech
1988), M.S. degree Biology (State University of Rio de Janeiro,
Brazil, 1982), Research Instructor, Department of Radiation
Oncology, East Carolina University, Has received several honors,
including fellowships from the Brazilian Nuclear Energy Commission,
the Brazilian National Division of Cancer, the German Government
for advanced training in Metrology of Ionizing Radiation, and from
the French Government for advanced training in dosimetry. Member
of both the Brazilian and American Association of Physicists. Has
served as an independent consultant for the National Institute for
Metrology Standard and Industry Quality in the areas of infant phototherapy equipment, diagnostic and therapeutic laser equipment, and
automatically-controlled brachytherpay afterloading. Has published
25 papers in pee-reviewed journals and over 80 scientific presentations in congresses and other peer reviewed meetings.
Ron R Allison M.D. Professor and Chairman of the Department of
Radiation Oncology and Clinical Director of the Photodynamic
Therapy Program. Physician specialized in Radiation Oncologist,
board certified in my specialty by the American Board of Radiology,
1992, and diplomat of the National Board of Medical Examiners in
1991. Served as Associate Professor at the State University of New
York at Buffalo form 1996-2001 and Professor at East Carolina
408