Nutrition and Orthomolecular

Supplementation in Lung Cancer Patients

Integrative Cancer Therapies

8(4) 398408
The Author(s) 2009
Reprints and permission: http://www.
sagepub.com/journalsPermissions.nav
DOI: 10.1177/1534735409344333
http://ict.sagepub.com

Diana Campos,1 Carlos Austerlitz,1 Ron R. Allison,1 Helion Pvoa,2

and Claudio Sibata1

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

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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

agents (carboplatin, taxol, cisplatin, gemcitabine, navelbine,

irinotecan, etoposide, vinorelbine adriamycin, bleomycin,
mitomycin C, nitrofurantoin, chlorpromazine); air pollution
(carbon monoxide, nitric oxide, aldehydes, alkyl nitrates);
ingested substances (alcohol, smoked and barbecued food,
peroxidized fats in meat and cheese, deep-fried foods); occupational and environmental exposures to metals; and
emotional stress.3
Antioxidants are molecules that neutralize free radicals
before vital molecules are damaged. Antioxidants include
(a) nutrients (vitamins A, C, and E, carotenoids, selenium,
flavonoids/polyphenols, lycopene, lutein, lignans, coenzyme Q10, glutathione); (b) enzymes synthesized in the
body (superoxide dismutase, catalase, glutathione peroxidase); although there are several enzyme systems within the
body that scavenge free radicals, the body cannot use these
enzymes without micronutrients (ie, Cu, Fe, Mn, Zn, and
Se), so they must be supplied in the diet.4 Oxygen

free-radical formation caused by oxygen metabolism and

ionizing radiation is shown in Figure 1.
Approximately 95% to 98% of the oxygen in the human
body is converted to water. The electron transport chain,
which is found in the inner mitochondrial membrane, uses
oxygen to generate energy in the form of adenosine triphosphate.5 Oxygen acts as the terminal electron acceptor within
the electron transport chain, but anywhere from 2% to 5%
of the total oxygen intake has the ability to form the highly
damaging superoxide anion (O2) radical via electron
escape. In the presence of Cu, Zn, and Mn, superoxide dismutase converts O2 to hydrogen peroxide (H2O2) or the
hydroxyl radical (OH). The H2O2 can then be neutralized
by the enzymes catalase and glutathione peroxidase. During
this process of neutralization, glutathione peroxidase
becomes oxidized and is regenerated by the glutathione
reductase enzyme. These enzymes can only work in the
presence of Fe (catalase), Se (glutathione peroxidase), and

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Integrative Cancer Therapies 8(4)

vitamin B2 (glutathione reductase). When the H2O2 is not

neutralized, it can interact with copper or iron to produce
OH by the Haber Weiss reaction, or with Fe++ to produce
OH by the Fenton reaction. These reactions are significant
as the substrates are found abundantly within the body.3 The
hydroxyl radical has no endogenous neutralizing enzyme
and can interact with fatty acids to form lipidic peroxide
(COOH-) or with nitric oxide (NO) to form a peroxynitrite
anion (ONOO-).
Because the human body consists of more than 75%
water, free radicals are produced from water by hydrolysis
when exposed to ionizing radiation. Singlet oxygen is
formed after water is exposed to ionizing radiation. Singlet
oxygen is not a true free radical but can transfer its energy
to a new molecule and act as a catalyst for free radical formation.
Table 1 outlines exogenous antioxidants that can be
used against all the free radicals listed. The enzymes
superoxide dismutase, catalase, glutathione reductase,
and glutathione peroxidase, which constitute endogenous
protection against free radicals, can only act against the
superoxide anions and hydrogen peroxide free radicals if
supplied with Mn, Zn, Cu, Fe, Se, and B2. Melatonin is
formed endogenously by the pineal gland and by the
intestinal cells. When these cells are damaged, for example, during a radiation treatment, there will be a decrease
in melatonin formation.6
Oxidative stress is defined as a disturbance in the equilibrium between reactive oxygen species (ROS) and detoxifying
antioxidant systems7 and can be involved in the pathophysiology of many diseases. Examples of conditions linked to
OS include the following: anemia and tumor hypoxemia8;
cardiomyopathy; bone and joint pain; bone marrow depletion;
cardiopulmonary damage9; endocrine and reproductive
impairment and dysfunction; normal tissue damage from
radiotherapy10; fatigue and compromised nutritional status,11
gastrointestinal dysfunction,9 and immunological complications12; local ischemia13; lung tissue injury; muscular
atrophy14; musculoskeletal sequelae9; myelodysplastic syndromes; numbness and tingling; osteopenia10; osteoporosis15;
pain; renal impairment9; respiratory complications16; malignancy10; thyroid abnormalities10; inflammation17; and aging.18
All these may influence response to cancer treatment and
outcome.

Antioxidants and Lung Cancer Prevention

Even though antioxidants have been associated with cancer
prevention, the cancer prevention community was stunned in
the early 1990s when the Alpha Tocopherol, Beta-Carotene
Cancer Prevention Study Group19 failed to show that b-carotene could prevent lung cancer in older male smokers. In this
study, Finnish smokers who were supplemented with synthetic b-carotene (20 mg 33000 UI/d) developed lung cancer

at significantly higher rate (18%) than those using a placebo.

An analysis of this study was presented by Gonzles et al in
1997.20 Out of 14 560 men on b-carotene, 474 developed
lung cancer, whereas of the 14 573 men on placebo, 402
developed lung cancer. The incidence increased from 2.76%
in the control group to 3.26% for the treated group. There
was an 18% relative increase in lung cancer in the b-carotene
group. However, the overall mortality from cerebrovascular
disease was reduced by 10% in those receiving antioxidants,
and the overall mortality was reduced by 7% in the supplemented group, which may also confound results. The most
relevant issues addressed by Gonzles et al about the Finnish
antioxidant and lung cancer study were related to the form of
supplementationlow doses, short duration of supplementationand other additional risks factors such as the
continuation of smoking. The form of supplement was synthetic and contained other ingredients (B-carotene and
vitamin E) and a-tocopherol/acetate from which some animals have increased tumor rates. Doses were only 1/8 to
1/40 of the intake used in previous clinical studies. Alcohol
consumption was not taken into account.
A recent review of the effect of b-carotene intake on
lung cancer development was published by Brar.21 It concluded that the current literature concerning b B-carotene
supplementation and lung cancer incidence may best be
summarized as inconclusive.
In a study done by Wright et al,22 the effects of a-tocopherol and b-carotene supplementation did not provide a
protective effect against upper aerodigestive tract cancers.
Nevertheless, subgroup analysis for larynx showed a protective effect of b-carotene supplementation on the incidence
of early stage malignancies.22 Additionally, the lack of
overall benefit of single agent b-carotene and a-tocopherol
supplementation contrasts with the strong inverse findings
for baseline dietary and serum antioxidants in relation to
esophageal and laryngeal cancers. These discrepancies
might have arisen because dietary antioxidants are likely to
exert their protective effects through interactions with other
vitamins and cofactors.
The effect of multiple (b-carotene, vitamin E, and
selenium) vitamins and minerals in the prevention of
esophageal cancer in a population with the highest
known rate for this disease in the world (China) is the
subject of an ongoing study.23 Early results have shown
that such supplementation reduced total mortality, total
cancer mortality, stomach cancer incidence and mortality, and premalignant lesions.
Therefore, supplementation with only a single antioxidant might be insufficient to achieve a beneficial effect.
Furthermore, pharmacological doses of antioxidants may
modulate the biological pathways differently than through
dietary means. It is also hypothesized that antioxidant trials
in patients who take a supplement for relatively short periods of time might not reflect the maximum benefit of

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Table 1. Free Radicals, Antioxidant Defense Network
Antioxidant
Free Radical

Exogenous
(O2-)

Superoxide anions
Hydrogen peroxide (H2O2)

b-Carotene, a-lipoic acid

Vitamin C, bioflavonoids, Se, N-acetylcysteine, carnosine,
melatonin39

Hydroxyl (OH-)
Oxygen, singlet (O2)
Lipidic peroxide (COOH-)

a-Lipoic acid, carnosine, melatonin39

b-Carotene, a-lipoic acid, carnosine, melatonin39
Vitamin E, a-lipoic acid

antioxidants compared with habitual consumption over

many decades.

Nutritional Supplementation in Lung Cancer Patients

Lung cancer has one of the lowest survival outcomes of
any cancer. Published international 5-year survival for
patients with lung cancer varies from 5% to 16%.24 A variety of treatment modalities are used to treat lung cancer,
including chemotherapy and radiation, both of which can
increase oxidative stress.24
Both nutrition and antioxidants influence oxidative
stress levels, and both may play an important role in the
prevention of cancer and treatment of cancer patients. Data
support the use of antioxidants in the prevention of gastrointestinal cancer,25 prostate cancer,26 and breast cancer. The
use of antioxidant and nutritional supplementation in cancer
patients has been reported to decrease inflammation, infection,27 cancer growth,28 mutation,29 malignant cell
proliferation and inducing differentiation,30 and dedifferentiation.31 In addition, supplementation has been associated
with palliation of pain32 and improved the quality of life of
terminal cancer patients.33
A study was conducted by Jatoi and collegues34 on the use
of voluntary vitamin and mineral supplementation on
non-small-cell lung cancer (NSCLC) patients from the Mayo
Clinic. A cohort of 1129 patients responded to a questionnaire on vitamin and mineral intake, which was then used to
assess survival and quality of life. The results show that
median survival was 4.3 years versus 2.0 years for vitamin/
mineral users and nonusers, respectively. The Lung Cancer
Symptom Scale showed better quality of life among vitamin/
mineral users (mean difference in score of 3 (95% confidence
interval = 0.8, 5.1; P < .01), and after adjusting for related
variables, there remained a trend in favor of vitamin/mineral
use with a mean difference of 1.8 (95% confidence interval =
0.2, 3.9; P = .08).
A similar study was done for small-cell lung cancer by
Jatoi and collegues.35 Based on a cohort of 178 patients, it
was stated that the median survival increased to 38% in
those who took vitamin and mineral supplements compared
with those who did not. However, there were no significant
improvements in the patients quality of life.

Endogenous
Superoxide dismutase (Mn, Zn, Cu)
Catalase (Fe), glutathione peroxidase
(Se), glutathione reductase (Vitamin
B2), melatonin
Melatonin39
Melatonin39

Simone and collaborators36 examined the interference of

antioxidants and other nutrients with chemotherapy or radiation therapy. The work involved 280 peer-reviewed published
studies (62 in vitro and 218 in vivo), including 50 human clinical studies that used nonprescription antioxidants and other
nutrients (8521 patients, 5081 of whom were given nutrients)
and 50 studies on prescription antioxidants. It was concluded
that published studies have consistently shown that nonprescription antioxidants and other nutrients do not interfere with
cancer therapeutic modalities. In addition, nonprescription
antioxidants and other nutrients enhance the killing of cancer
therapeutic modalities, decrease their side effects, and protect
normal tissues, and in 15 human studies, 3738 patients actually
had prolonged survival.
There are few findings in the scientific literature related
to dietary intervention and supplementation specifically for
lung cancer patients.37 Sun and colleagues examined the
effect of the intake of 30 g daily of Sun Farm soup freezedried powder (DSV) for NSCLC (stages III and IV) on 24
patients. The soup contains water, soybean, shiitake mushroom, mung bean, red date, scallion, garlic, lentil bean,
leek, hawthorn fruit, onion, American ginseng, angelica
root, licorice, dandelion root, senegal root, ginger, olive,
sesame seed, and parsley. The primary endpoint of this
study was death or survival measured up to 24 months from
date of entry. Median and mean survival was 4 and 4.8
months in control patients and 15.5 and 15 months in treatment patients (P < .01). Weight maintenance and Karnofsky
performance status were also improved.
Another report by Sun et al,38 involved a small openenrollment trial to evaluate the survival of 18 volunteer, stage
IIIB and IV NSCLC patients consuming 283 g daily of thawed
selected vegetables (FSV) alone or as an adjuvant to conventional therapy, compared with historical controls. The mean
and median survival times of eligible NSCLC patients using
FSV were 23.7 and 33.5 months, respectively. The historical
mean survival time is 7 months. One-year survival of FSV
patients was 71%.
In summary, effective dietary intervention and supplementation has been associated with less weight loss and
improved survival in lung cancer patients.37,38 Quality of
life measured by the quality-of-life index increased significantly, and weight loss was decreased for advanced lung

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Integrative Cancer Therapies 8(4)

cancer patients undergoing aggressive chemotherapy with

supplemented diets for 2 months.39 A multivariate analysis
demonstrated that lung cancer patients on a diet with 25%
of calories from protein and supplemented with zinc and
magnesium had less weight loss and higher serum albumin
concentrations, which were also significant and independent prognostic variables for survival duration.39 Although
these are promising results, there is a need for large randomized placebo-controlled trials.

Complication of Treatment and Nutritional

Intervention
Lung cancer treatment is often aggressive and may induce
morbidity. The clinical consequences of lung cancer treatment
may lead to complications including: oral mucosa and intestinal lining damage, leading to oral or esophageal candidiasis,
inflammation, taste loss, nausea, vomiting, diarrhea, and
anorexia. All these symptoms constitute a heavy burden for
the patients and their caregivers. When proper oral nutrition is
impaired, it can be replaced by means of supplementation
(vitamin, minerals, amino acids, etc).

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

oxidative stress as reflected by higher levels of malondialdehyde and nitrite.

Cachexia is clinically characterized by progressive weight
loss, anorexia, metabolic alterations, asthenia, depletion of
lipid stores and severe loss of skeletal muscle proteins. It is
present in about 50% of cancer patients and accounts for 20%
of all cancer deaths. Proinflammatory cytokines and oxidative stress/antioxidant parameters characterize the biohumoral
profile of early cachexia in lung cancer patients. This has
been reported by Fortunati et al.42 The findings of ROS,
reduced glutathione and vitamin E, and elevated a-proinflammatory cytokines allows the identification of a lung
cancer patient developing cancer-related cachexia.
Todisco et al43 in an early study reported on the treatment of cancer with a combination of chemotherapy and
nutrition supplements. They combined cyclophosphamide,
somatostatin, bromocriptine, retinoids, melatonin, and
adrenocorticotropic hormone. In a phase II trial, the abovementioned medications were well tolerated and effective
in treatment of low-grade non-Hodgkin lymphoma at an
advanced stage. The response of somatostatin, retinoids,
melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced NSCLC patients with low performance
status has been published by Norsa and Martino.44 From
this study of 28 patients, it was concluded that the combined regimen of such medications is active in the
treatment of chemotherapy-nave patients with advanced
NSCLC and poor performance status, in terms of both survival and quality of life, and presents very mild side
effects. The rationale for this pharmacological association
was based on the following: (a) both growth hormone and
prolactin are released, which are 2 hormones involved in
neoplastic growth that are inhibited by somatostatin and
bromocriptine,45 respectively; (b) retinoids, such as vitamin A and its analogs, regulate cell growth, and immune
function46; (c) melatonin is endowed with immunostimulant properties47; and (d) each of the proposed
biotherapeutical agents has specific antitumoral effects. A
similar study was performed by the same authors using a
group of 23 pretreated patients with advanced lung adenocarcinoma and low performance status.48 In this case,
vitamin E was added to the above-mentioned combined
regime. It was concluded that this combined regimen is
also well tolerated and can be effective in improving disease-related symptoms in heavily pretreated patients with
late-stage lung adenocarcinoma.
A study was conducted by Jaakkola et al49 on small-cell
lung cancer in humans using combination chemotherapy of
cyclophosphamide, Adriamycin (doxorubicin), and vincristine with radiation and a combination of antioxidants,
vitamins, trace elements, and fatty acids. The conclusion
was antioxidant treatment, in combination with chemotherapy and radiation, prolonged the survival time of patients
compared with expected outcome without the composite
oral therapy.

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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.

Clinical Aspects of Supplementation

During and after treatment, lung cancer survivors may benefit from eating foods that provide concentrated calories that
are easy to swallow. Small, frequent meals may be easier to
manage than 3 large meals per day. Omega-3 fatty acid supplements and additional nutritional support may be helpful
for those patients experiencing weight loss. If nutrient deficiencies are present or patients cannot eat enough to
adequately meet micronutrient needs, a multivitamin
mineral supplement is advisable, either in pill or liquid
form. Recommendations for nutrition and physical activity
for persons who are living with lung cancer are best made
based on individual needs. Striving toward a healthy weight
by adjusting food intake and physical activity is a reasonable
goal, as is ensuring that micronutrient needs are met with a
well-balanced diet and a multivitaminmineral supplement,
if needed.52 In addition, intestinal absorption, which could
be affected by radiation, chemotherapy, or poor nutrition
may be improved by using the amino acid glutamine and
lactobacillus.53
Because many lung cancer patients die from cachexia
malnutrition, a basic list of orthomolecular supplements
and a nutritional protocol with emphasis on this disease are
given in Table 2 and Table 3, respectively. For a supplementation to be effective, various factors need to be considered,

including (a) the patients medical history, (b) clinical and

laboratory tests (including mineral hair analysis), (c) the
appropriate antioxidant dose for prevention and treatment,
(d) use of chelated mineral supplements to improve their
absorption, (e) use of combinations of antioxidants for
potential synergy, and (f) the patients food intake and lifestyle. In addition, knowledge of the patients intestinal
absorption status (ie, pH, and permeability) is imperative
because intestinal malabsorption may compromise the
effectiveness of supplementation.

Antioxidant Protocol and Nutritional Questionnaire

for Lung Cancer Patients
Lung cancer is largely related to cigarette smoking, but
diets low in vegetables and fruits have also been associated
with increased lung cancer risk, even after accounting for
tobacco use.54 Both these risk factors are associated with
increased oxidative stress. As previously discussed,
enzymes, minerals, and vitamins play an important role in
oxidative stress control. However, the response to treatment
may also be influenced by the patients comorbidities,
which can offset the oxidative status, such as hypertension,
obesity, diabetes, and intestinal dysfunctions. Unfortunately,
there are no studies in the literature exploring a customized
orthomolecular protocol for oncological patients, including
antioxidant combinations and nutritional aspects. In addition, studies analyzing lung cancer patients blood, feces,
and minerals from, for example, hair during chemoradiotherapy to determine the level of oxidative stress are
lacking.

Lung Cancer Patient Status via Questionnaire

and Lab Analysis
We have previously reported results from profiles of vitamins, minerals, and amino acids in lung cancer patients
undergoing radiation therapy.55 This was based on analytical laboratory tests and nutritional questionnaires from a
cohort of 10 NSCLC patients.
The analytical tests included hair elements analysis of
toxic elements (Al, Sb, As, Be, Ca, Bi, Cd, Pb, Hg, Pt, Tl,
Th, U, Ni, Ag, Sn, and Ti) and essential elements (EEs;
Ca, Mg, Na, K, Cu, Zn, Mn, Cr, V, Mo, B, I, P, Li, Se, Sr,
S, Ba, Co, Fe, Ge, Rb, and Zr), amino acids profile on
plasma (alanine, a-amino adipic acid, a-amino butyric
acid, arginine, asparagine, aspartic acid, b-amino isobutyric acid, b-alamine, citruline, cystathione, ethanolamine,
g-amino butyric acid, glycine, glutamic acid, glutamine,
hydroxyproline, histidine, homocystine, isoleucine, leucine, lysine, methionine, ornithine, phenylalamine,
proline, sarcosine, serine, taurine, threonine, tyrosine,
tryptophan, valine, 1-methylhistidine, 3-methylhistisdine), fecal analysis (ova and parasites may impair
medication and nutrient absorption), whole blood analyses

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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.

Table 3. Basic Protocol to Modulate Cancer Cachexia

Objective
Nutrition

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

improve outcomes and quality of life. However, variables

that may influence the levels of biological indicators independently of exposure (eg, geographical areas to identify air
pollution, source of water supply) were not taken into
account.
The present study provides initial compelling data about
the potential benefits of the use of vitamin/mineral supplements as adjunctive therapy for cancer patients. However,
there is a need to standardize a nutritional questionnaire and
to implement an individualized regime of antioxidants for
lung cancer patients according to the treatment protocol and
the particular patients life condition, with clinical correlation
and evaluation of both the benefits and consequence of this
approach.

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

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Integrative Cancer Therapies 8(4)

University from 2001 to present. Has conduct manuscript reviews

for 15 scientific journals. Has published over 65 scholarly scientific
papers in peer-reviewed journals. Has authored 5 book chapters in
radiation oncology and photodynamic Therapy. Has made numerous
invited presentations in national and international events and has
been awarded 7 extramural funded grants. Has received several
awards and honors and I am listed in the Whos Who in Fluorescence
2006, and Who's Who in Medicine Academia, since 2006.
Helion Pvoa MD, Federal University of Rio de Janeiro, Brazil.
Researcher from the Osvaldo Cruz Foundation. Visiting professor of
nutrition in the school of public health from Harvard, Professor of
clinical biochemistry in post-graduate of the Pontificia Catholic
University of Rio de Janeiro, Brazil. Has published overr 400
research papers in journals congresses and meetings. He is a member
of the National Academy of Medicine and the founder and director
of Center for Advanced Medicine, CLINICE, Rio de Janeiro, Brazil.
Has authored 4 book in the field of orthomolecular.
Claudio H Sibata Ph.D. degree in Medical Physic from the
University of Wisconsin in Madison in 1984. Professor and

Vice-Chairman in the Department of Radiation Oncology and

Science Director of the Photodynamic Therapy Center of the Brody
School of Medicine at East Carolina University. Received several
awards and honors, including Inventor of the Year Award in 2009,
East Carolina University and Fellow of the American Association of
Physicists in Medicine. Member of the International Photodynamic
Association, American Association of Physicists in Medicine,
American Society for Therapeutic Radiology and Oncology,
Brazilian Association of Physicists in Medicine, European Society
for Therapeutic Radiology and Oncology, and Argentinean Society
of Physicists in Medicine. Have supervised more than 35 graduate
and post graduate students and fellows. Has served as examiner for
the American Board of Radiology since 2000. Physics surveyor sine
2002 for American College of Radiation Oncology and have surveyed over 150 radiation oncology departments since then, Serve as
reviewer in several editorial boards of scientific journals such as the
Physics in Medicine and Biology, the Medical Physics, the Lancet
Oncology, and the International Journal of Radiation Oncology
Biology Physics. Has published over 100 scholarly scientific articles
in peer-reviewed journals and co-authored 5 chapters in medical
physics books and 6 books/monographs.

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