Int. J.

Cancer: 125, 11551160 (2009)

' 2009 UICC

Cod liver oil, other dietary supplements and survival among cancer patients with
solid tumours
2
Guri Skeie1*, Tonje Braaten1, Anette Hjartaker

, Magritt Brustad1 and Eiliv Lund1

1
Institute of Community Medicine, University of Troms, Troms, Norway
2
Cancer Registry of Norway, Oslo, Norway

The effect of various dietary supplements on chronic diseases and

mortality has been widely studied, but few convincing results have
emerged from studies in well-nourished populations. In Norway,
both cod liver oil and other dietary supplements are frequently
used. In the Norwegian Women and Cancer cohort study, we
explored if supplement use before diagnosis affected survival of
cancer patients with solid tumours. We performed Cox proportional hazards analyses, adjusting for age at diagnosis, smoking
and stage. Cod liver oil was the most frequently used dietary supplement, followed by multivitamins and -minerals. Whole year
daily use of cod liver oil was associated with lower risk of death in
patients with solid tumours [RR 5 0.77 (95% CI 0.610.97)] and
in lung cancer patients [RR50.56 (95% CI 0.340.92)]. Also daily
and occasional use of other dietary supplements decreased the
risk of death among lung cancer patients [RR 5 0.70 (95% CI
0.490.99) and 0.55 (95% CI 0.310.97)]. More research is needed
to clarify the association; meanwhile adjustment for dietary supplement use should be performed in survival analyses of lung cancer patients.
' 2009 UICC

CLO is the second most important dietary source of very-longchain fatty acids in the Norwegian diet (after fish) and women in
the highest quartile of very-long-chain fatty acid intake have a
more than tripled intake of vitamin D compared with those in the
lowest quartile.17 Intake of these nutrients alone or in combination has been associated with a range of health effects and
mortality.1825 The main source of vitamin D is solar ultraviolet
B-radiation which induces vitamin D3 production in the skin.18
From 51 degrees north and northwards, there is a period each year
with no or very low cutaneous production, which increases in
length with latitude.26 All of Norway is north of this latitude, so in
periods of the year dietary intake of vitamin D is necessary to
cover the requirements.27,28
The aim of this study was to compare the survival of female
cancer patients with solid tumours according to use of CLO and
other dietary supplements before diagnosis. We present overall
survival for all solid tumours, and separate estimates for patients
of the most frequent cancer sites: breast, colorectum and lung.

Key words: cancer patients; survival; dietary supplements; cohort

study; Norway

Material and methods

Dietary supplement use is increasing and several studies have

shown higher use among cancer patients than in the general population.1 Dietary supplements comprise a wide range of products of
differing composition. Studies of their effects on primary prevention of chronic diseases, as well as mortality, have generally failed
to demonstrate beneficial effects in well-nourished populations.27
Clinical trials have also been stopped early due to no preventive
effects and suggestions of negative health effects, a recent example is the SELECT study.8 The second WCRF/AICR expert report
summarized that there is not enough evidence yet for giving specific advice to cancer survivors, neither on supplement use nor on
other dietary factors. They, therefore, suggest that survivors follow general cancer preventive advice, which is not taking supplements, but try to meet nutritional needs through diet alone.6
The American Cancer Society has developed guidelines for
nutrition and physical activity during and after cancer treatment,
even though they know that the scientific evidence is incomplete.9
During and after cancer treatment, a standard multiple vitamin and
mineral supplement containing approximately 100% of the daily
value is recommended, since it might be difficult to eat a diet with
adequate amounts of micronutrients in those times. However, no
evidence was found to suggest that nutritional supplements lower
risk of recurrence. Use of high-dose supplements is discouraged.9
There is some concern that high-dose antioxidant supplements
might interfere with radio- or chemotherapy treatments, though
this is somewhat controversial.9,10
Dietary supplement use is common in Norway, and the most
commonly taken dietary supplement is cod liver oil (CLO).1114
Typically 35% of the female adult population takes it daily at least
during winter. Also other supplements are taken frequently and
4060% of Norwegian women report use of other supplements.11,15 Compared with healthy women, Norwegian breast cancer survivors did not have a significantly higher consumption of
CLO, but used other dietary supplements at a higher frequency.16
The difference was limited to those surveyed rather shortly (15
years) after diagnosis.
Publication of the International Union Against Cancer

The Norwegian Women and Cancer study was initiated in 1991,

and is a national, population-based cohort study. The study design,
population and procedures have been described elsewhere,
together with aspects of external validity.29 This article reports information collected between 1996 and 1999, partly from the second part of the baseline mailing (19961997), and partly from a
second mailing (19981999). In total, 68,518 women filled in a
self-administered questionnaire including a semi-quantitative
food-frequency questionnaire (FFQ) and questions on demographic variables, reproductive factors, lifestyle factors, medication, different illnesses, smoking, physical activity, education and
income. Body mass index (BMI) was calculated as weight (kg)
divided by the square of the height (m2).
Dietary questionnaire and calculations
The FFQ covered the habitual diet in the previous year, with
special attention to the consumption of fish and fish products.30
The questionnaires applied in the baseline and the second mailing
had comparable sections of dietary information, but with some differences, especially in sweet foods. It included 6678 food items
typically consumed in Norway, several questions on CLO and
other dietary supplements (see details below) and 3 questions on
alcohol intake, but did not cover the entire diet. Frequencies were
asked per day, week, month or year as appropriate, typically with
67 alternatives. A more detailed description of the core dietary
questions and their validation has been published elsewhere.3033
Daily intake of nutrients and energy was calculated using values
from the Norwegian Food Composition table.34 This table
Grant sponsor: The Norwegian Foundation for Health and Rehabilitation
(EXTRA funds) and the Norwegian Cancer Society.
*Correspondence to: Institute of Community Medicine, University of
Troms, N-9037 Troms, Norway. Fax: 147-77644831.
E-mail: guri.skeie@uit.no
Received 5 January 2009; Accepted after revision 26 February 2009
DOI 10.1002/ijc.24422
Published online 11 March 2009 in Wiley InterScience (www.interscience.
wiley.com).

1156

SKEIE ET AL.

includes data on CLO, but not on other dietary supplements. CLO

(liquid and capsule concentrates) was, therefore, the only dietary
supplement included in the nutrient calculations. No dietary supplements database was available to confirm the content of the
other dietary supplements. However, supplement names were
extracted from all lung cancer patients and a random selection
(22.5%) of other cancer patients (not restricted to solid tumours)
who had reported this. Based on the names, main ingredients and
frequency of use, the other dietary supplements were classified in
9 categories (Table I). Multivitamins and -minerals were the most
frequently used other dietary supplement type, followed by vitamin Bs and C. The pattern of use did not differ between the 2
groups.
Cod liver oil and other dietary supplement use
For about 2/3 of the cohort there were initial yes/no questions
on liquid CLO use, CLO capsule use and use of other dietary supplements. Next, the participants were asked separate questions on
how often they took liquid CLO, CLO in capsules and other dietary supplements: never/seldom, 13 times a month, once a week,
26 times a week or daily. For about 1/3 of the cohort no initial
yes/no questions were asked, and the option 26 times a week was
split into 23 times and 46 times a week. All participants were
asked separate frequency questions about CLO use (liquid and
capsules) in the winter and the rest of the year. Finally, a question
on CLO dose was asked, the alternatives were 1 teaspoon, 1/2
tablespoon or 1 tablespoon for liquid CLO, and the number of
CLO capsules was queried. For other dietary supplement there
was an open-ended question about supplement name(s), but no
question on dose.
A previous analysis have shown that use of CLO is associated
with several sociodemographic factors, self-reported health issues
and intake of fish, fruit and vegetables in our cohort.11 For the current analyses, 4 groups of CLO-users were created based on the
categories in the questionnaire and the previous paper11: nonusers, occasional users, seasonal daily users and whole year
daily users. Participants were classified as non-users if they
never took CLO, or did so less frequently than once a week during
winter and the rest of the year. Occasional users were defined as
participants taking CLO 16 days per week either during the winter months or the rest of the year or both. Seasonal daily users
were defined as subjects taking CLO daily either during winter or
the rest of the year. Whole year daily users were those taking
CLO daily both in the winter and the rest of the year. The analyses
did not discriminate between CLO consumed in liquid and capsule
form. Daily users of CLO taking the recommended dose will cover
their vitamin D requirements. For other dietary supplements the
categories were non-users, occasional users and daily users.
These categories were constructed in a similar fashion as the
CLO-categories, but without seasonal variation.
To check the combined effect of CLO and other supplements, a
new variable combining the two was created. Non-users of both
types of supplements were the reference category, the other categories were: occasional users of one or both types (including
any combination of occasional/non-use, occasional/occasional
and occasional/daily), daily users of CLO (whole year or seasonal)
not using other supplements, daily users of other supplements not
using CLO, and daily users of both CLO and other supplements.
Study population
Information on cancers was obtained by linkage to the Cancer
registry of Norway and information about death was obtain from
the Central Person Registry, both using the individually unique
national registration numbers. The Regional Committee for Medical Research Ethics and the Norwegian Data Inspectorate
approved the study. All participants provided informed consent.
The study population was the subsample of the cohort who was
diagnosed with their first cancer after the 19961999 questionnaire, and before January 1, 2007, N 5 4,242. Exclusions were

TABLE I TYPES OF DIETARY SUPPLEMENTS USED BEFORE DIAGNOSIS

BY LUNG CANCER PATIENTS AND OTHER CANCER PATIENTS WHO
REPORTED SUPPLEMENT NAMES
Supplement type

Multivitamins/minerals
Vitamin B
Vitamin C
Ginseng/Q10
Vitamin E
Single minerals
Herbs/plants
Other
Not specific
Total

Lung cancer
patients (n 5 87)1

Other cancer
patients (n 5 239)1

38.5
15.6
14.1
10.4
5.9
5.9
5.2
3.0
1.5
100.0

52
21
19
14
8
8
7
4
2
135

38.2
11.4
12.8
9.7
6.7
8.1
4.5
7.2
1.4
100.0

137
41
46
35
24
29
16
26
5
359

1
Since several patients took more than one supplement, the number
of supplements taken is greater than the number of patients.

based on implausible energy intakes (<2,500, >15,000 kJ/day)30

(N 5 52), missing information on smoking (N 5 87), missing information on CLO frequency or amount (N 5 325), and missing
information on frequency of other supplements, (N 5 132). A further 20 patients were diagnosed upon death and did not contribute
follow-up time and 629 patients did not have stage information
(including 239 non-solid tumours). Finally, 2,997 women were
included in the analyses; 1,226 with breast cancer [International
Classification of Diseases version 7 (ICD-7), code 1700-1709],
399 with colorectal cancer (ICD-7, code 1530-1549), 217 with
lung cancer (ICD-7, code 1620-1629) and 1,155 with other solid
tumours. The vital status was censored December 31, 2007, and
by then 748 participants had died, of these 121 had breast cancer,
143 had colorectal cancer and 160 had lung cancer.
Statistical analyses
The Cox proportional hazards model was used to calculate hazard ratios for mortality with corresponding 95% confidence intervals (CI). Assumptions for the Cox proportional hazards model
were tested and met. The hazard ratios are interpreted as estimates
of relative mortality risks (RR), and the term survival is used analogously to mortality risk. Time since diagnosis was used as the
primary time-variable. KaplanMeier plots were constructed to
describe the survival function. Survival differences between
groups were assessed for statistical significance by the log-rank
test. Differences between categories of CLO and other supplement
use were tested in analyses of covariance (age at diagnosis) and
Cochran-Mantel-Haenzels test adjusted for age at diagnosis
(smoking and stage). All analyses were done in SAS Software
Package (version 9.1). The level of significance was set to 0.05.
The associations between cancer survival and CLO and other
dietary supplements use, respectively, were first examined in ageadjusted analyses. A set of potential confounders were tested individually in a model with age and supplement use, and whenever a
change in risk by supplement use was observed, the variable was
included in the multivariate models. The criterion for effect was a
change in the estimate for supplement use of 5% or more in the
multivariate adjusted model. The following variables were tested
for confounding effects: stage, BMI, smoking status, physical
activity, age at first birth, parity, region of residence, education,
prevalence of certain diseases (myocardial infarction, stroke, high
blood pressure, heart failure and diabetes), self-reported health,
alcohol consumption, total fat, total energy, vitamin C, vitamin D,
beta-carotene, alpha-tocopherol, selenium, dietary fibre, fruits,
vegetables, fatty fish and lean fish. Only smoking status and stage
affected the estimates. The final models, therefore, only included
age at diagnosis (continuous, in years), smoking (never, former,
current) and stage (localized, regional metastases, distant metastases). Interaction between smoking and dietary supplement use

DIET SUPPLEMENTS AND SURVIVAL IN CANCER PATIENTS

was tested by including an interaction term in the models for total

cancer.
Results
Mean age at diagnosis was 58.4 years, but there were differences among the cancer sites, and breast cancer patients were
younger (Table II). More than half of the solid tumours were
detected at a localized stage, but there was considerable variation
among cancer sites. Most breast tumours were localized (57.3%),
most colorectal tumours were found with regional metastases
(64.9%) and tumours in the lung were most frequently detected
when distant metastases had occurred (45.6%). For all patients
(n 5 2,997), breast cancer patients (n 5 1,226) and colorectal cancer patients (n 5 399), the distribution between current, former
and never smoking before diagnosis was fairly even, but among
lung cancer patients (n 5 217) only 3.9% were never smokers.
Among all patients, 46.6% used CLO at least occasionally before
diagnosis, with slight variations between the cancer sites. The frequency of other supplement use before diagnosis was similar,
47.1%, also with slight variation between cancer sites.
Some differences were observed across categories of CLO and
other supplement use (results not shown). Nonusers and occasional users of CLO were younger (58 years) than seasonal (59
years) and whole year (61 years) daily users (p < 0.001). Smoking
was significantly associated with CLO use, p 5 0.005. There were
more current smokers among nonusers (38.9%) than occasional
users (28.2%). Occasional users of other supplements were
younger at diagnosis (56 years) than nonusers and daily users (59
years, p < 0.001). Stage was significantly associated with other
supplement use (p 5 0.02). Occasional users were more often
diagnosed in a localized stage of disease (57% of the cases vs.
52% in nonusers and daily users), and less often with distant
metastases (9 vs. 14% and 11%). One-year survival rate differed
vastly, for breast cancer it was 98.4%, for colorectal cancer 86.7%
and for lung cancer 47.0%.
In Figure 1 KaplanMeier plots for all solid tumours (Fig. 1a)
and lung cancer (Fig. 1b) describe the survival function for the
categories of CLO use, and figures 1c and 1d have corresponding
plots for categories of other dietary supplement use. For CLO use
there were no differences either for all solid tumours or for lung
cancer. One-year survival rate for all solid tumours was 89.8% for
whole year daily users, 88.9% for seasonal daily users and occasional users and 87.4% for nonusers. For lung cancer, it was
57.6% for all year daily users, 56.1% for seasonal daily users,
40% for occasional users and 42.4% for nonusers.
For other dietary supplements there was a significant association between category of use and survival. The log-rank test for all
solid tumours was significant (p 5 0.002), and occasional users
had the best survival. The 1-year survival was 89.3% among daily
users, 91.1% among occasional users and 86.9% among nonusers.
Also for lung cancer there was a significant association (p 5 0.02)
and occasional users had the best survival. One-year survival rate
was 52.8% for daily users, 58.3% for occasional users and 41.3%
for nonusers. As can be seen from the figures, the tendency was
that the curves diverged more as time since diagnosis increased.
Table III shows the relative risks of dying among cancer
patients with solid tumours depending on category of CLO use
and category of other supplement use. Whole-year daily use of
CLO was associated with improved survival among cancer
patients with solid tumours, RR 5 0.77 (95% CI 0.610.97). No
associations were evident for breast or colorectal cancer patients,
but lung cancer patients using CLO daily the whole year had a significantly reduced risk of death, RR 5 0.56 (95% CI 0.350.92).
Occasional users of other dietary supplements had the lowest
risk of death, both for all solid tumours and for the specific cancers
studied, but the risk reduction was only significant for lung cancer
patients, RR 5 0.55 (95% CI 0.310.97). For lung cancer patients,
the risk estimate for daily users was also similar, RR 5 0.70 (95%

1157

CI 0.490.99). There was no interaction between smoking and use

of CLO or other supplements.
More than half of those who died did so within 1 year of diagnosis. Specific causes of death were complete until December 31,
2005, and 95% of the deaths were due to cancer. Exclusion of
those diagnosed less than 1 year after study entry did not affect
the estimates.
When use of CLO and other dietary supplements were combined into one variable daily use of both CLO and other dietary
supplements was associated with improved survival in lung cancer
patients, RR 5 0.57 (95% CI 0.350.94; results not shown).
Discussion
In this study, daily use of CLO and other dietary supplements
before diagnosis, alone or in combination, was associated with
reduced risk of death among lung cancer patients. Survival was
also increased for cancer patients with solid tumours who were
whole-year daily users of CLO and for lung cancer patients using
other dietary supplements occasionally.
Our study is not the first to find increased survival in lung
cancer patients taking dietary supplements.3537 In a small crosssectional study a random selection (n 5 36) of postoperative nonsmall cell lung cancer patients were invited to complete a food
frequency questionnaire and donate a blood sample.35 The vitamin-users had significantly longer median disease-free survival at
the time of the study compared with nonusers, 41 vs. 11 months
(p 5 0.002). The second study was a prospective study of nonsmall cell lung cancer patients in the Mayo Clinic lung cancer
cohort.36 The 1,129 participants received a supplement questionnaire 6 months after diagnosis, and later at regular intervals. The
relative risk of death was 0.54 (95% CI 0.440.65) among current
users compared to non-users. After adjustment for stage, grade,
treatment modality, age, gender, smoking history at diagnosis and
timing of questionnaire, the RR increased to 0.74 (95% CI 0.60
0.91, p < 0.01). Median survival was 4.3 years for users vs. 2.0
years for nonusers. Similar results were found in patients with
small cell lung cancer, RR 5 0.65 (95% CI 0.431.00).37 In all
these studies, multivitamins were the most frequently reported
supplements.
Other studies have looked at biochemical or clinical indices of
nutritional status in relation to survival of lung cancer patients.
One study found that in early stage non-small cell lung cancer
patients, higher levels of circulating vitamin D was associated
with improved survival.38 However, the authors could not replicate the results in advanced stage nonsmall cell lung cancer
patients.39 Another study found that nutritional status on diagnosis
affected long term survival after lobectomy for lung cancer.40
Currently, the bulk of evidence on diet and cancer relates to primary prevention, and cancer survivors are advised to follow general cancer preventive strategies.6 At least 2 studies, including one
Norwegian study, have found that CLO supplementation lowers
lung cancer incidence.41,42 To our knowledge, no randomized control study of CLO supplementation and cancer incidence or survival has been performed.
Given that randomized controlled trials have demonstrated no
effects or increased incidence of lung cancer in supplementation
studies in well-nourished populations,43,44 our results may be
somewhat surprising. However, these studies used pharmacological doses of specific nutrients, and cannot easily be compared with
ours. The French SU.VI.MAX study on the other hand used a
combination of antioxidant vitamins and minerals at nutritional
doses in a general population, and found reduced total cancer risk
and total mortality in men, but not in women.45 Incidentally, the
difference in cancer rates was highest for cancers of the respiratory tract.
The SU.VI.MAX study found no differences in cancer rates for
women, and suggested that this was due to the higher baseline
concentrations of some antioxidant nutrients in women.45 It is

1158

SKEIE ET AL.
TABLE II CHARACTERISTICS OF ALL STUDY PARTICIPANTS AND PARTICIPANTS WITH THE MOST FREQUENT CANCER TYPES
Characteristic

All patients with solid tumours

(n 5 2,997)

Age at diagnosis (years, mean)

58.4
Stage (%)
Localized
52.4
Regional metastases
35.4
Distant metastases
12.2
One-year survival rate (%)
88.2
1
Smoking before diagnosis (%)
Never smokers
34.8
Former smokers
29.3
Current smokers
35.9
Cod liver oil use before diagnosis (%)1
Nonusers
53.4
Occasional users
10.2
Seasonal daily users
24.0
Whole-year daily users
12.4
Other dietary supplement use before diagnosis (%)1
Non-users
52.9
Occasional users
10.6
Daily users
36.5

Breast cancer patients

(n 5 1,226)

Colorectal cancer patients

(n 5 399)

Lung cancer patients

(n5 217)

56.6

61.1

60.3

57.3
40.0
2.7
98.4

25.3
64.9
9.8
86.7

17.5
36.9
45.6
47.0

37.4
31.5
31.1

33.3
36.5
30.2

3.9
12.6
83.5

52.5
10.4
24.6
12.5

58.6
6.4
24.0
11.0

56.4
11.6
18.1
13.9

51.5
11.1
37.4

55.9
9.1
35.0

55.7
11.7
32.6

Smoking, cod liver oil and other supplement use are adjusted for age at diagnosis.

FIGURE 1 KaplanMeier survival plot (a,b) for all solid tumours and lung cancer according to cod liver oil (CLO) use, respectively; (c,d) for
all solid tumours and lung cancer according to other dietary supplement use.

likely that our participants had lower intakes of antioxidant vitamins from foods than the French women4648 and therefore might
benefit from supplementation as the French men did. Also, the frequency of smoking among Norwegian women is much higher than
in French women.49
There are pros and cons to assessing supplement use before
diagnosis. Prediagnosis assessment helped assuring complete follow-up, including also those who died shortly after diagnosis, and
would often not be included in patient cohorts. Prediagnosis
assessment might also be a better indication of long-term use, as
cancer patients are known to initiate dietary supplement use after
diagnosis.1

One reason for taking supplements might be self medication,

either for preventive or curative effects. We excluded those who
had a period shorter than 1 year between the questionnaire and
diagnosis in case some of the participants had initiated supplement
use as a response to early symptoms. However, this had no effect
on survival estimates, and it is not likely that supplement users
were in poorer condition than nonusers. Given the higher proportion of occasional supplement users diagnosed with a localized
disease, it is more likely that at least a fraction of the supplement
users was more health conscious, went more often to the doctor
and was diagnosed earlier. Still, even after adjustment for stage
the supplementation effect remained for lung cancer patients.

1159

DIET SUPPLEMENTS AND SURVIVAL IN CANCER PATIENTS

TABLE III RELATIVE RISKS WITH 95% CONFIDENCE INTERVALS OF MORTALITY AMONG CANCER PATIENTS WITH SOLID TUMOURS BY CATEGORY
OF COD LIVER OIL (CLO) AND OTHER DIETARY SUPPLEMENT USE1
Use of cod liver oil and other dietary supplements

All solid tumours, 748 deaths

Breast cancer, 121 deaths

Colorectal cancer, 143 deaths

Lung cancer, 160 deaths

Nonusers of CLO
Occasional users of CLO
Seasonal daily users of CLO
Whole year daily users of CLO
Nonusers of other dietary supplements
Occasional users of other dietary supplements
Daily users of other dietary supplements

1.00 (ref)
1.05 (0.811.36)
0.98 (0.821.16)
0.77 (0.610.97)
1.00 (ref)
0.83 (0.621.10)
0.94 (0.801.09)

1.00 (ref)
1.37 (0.752.51)
0.95 (0.611.48)
1.30 (0.732.30)
1.00 (ref)
0.66 (0.321.33)
1.01 (0.691.47)

1.00 (ref)
0.46 (0.181.13)
0.98 (0.671.44)
0.82 (0.481.41)
1.00 (ref)
0.65 (0.301.43)
1.19 (0.841.69)

1.00 (ref)
1.16 (0.711.88)
1.03 (0.671.59)
0.56 (0.350.92)
1.00 (ref)
0.55 (0.310.97)
0.70 (0.490.99)

Adjusted for age at diagnosis and smoking (never, former, current) and stage (localized, regional metastases, distant metastases).

The use of prediagnosis as opposed to postdiagnosis supplement

information may also be drawback, since some of the patients
might change (most likely increase) their supplement use after diagnosis. Whether pre or postdiagnosis use is most relevant
depends on what is the critical period for influencing survival, and
whether short-term or long-term use is most important. If the most
relevant period for supplementation is after diagnosis, it is likely
that our results underestimate the effect of supplementation, as
some of the patients most likely have initiated supplementation.
On the other hand, if a certain level of the nutrients or long-term
supplementation is required for an effect, dietary supplement use
before diagnosis might be more relevant for the association with
survival. And if dietary supplement use only is an indicator of a
set of health behaviours or beliefs, prediagnosis use might be
more important, as these characteristics probably are stronger in
those who already take supplements before diagnosis, than in
those who initiate use afterwards.
Unfortunately, no dietary supplement database was available to
confirm the contents of the dietary supplements other than CLO
used in our study, so it is not possible to attribute the observed
association to antioxidants, or any particular nutrient. Since both
CLO and other supplements seem to have similar effect, and since
multivitamins and -minerals were most frequently reported among
other supplements, it is possible that the observed associations are
more due to health consciousness than particular nutrients. The
dominance of multivitamins and -minerals suggests that the majority of the other dietary supplements contained nutritional, not
pharmacological doses of nutrients. Also, for other dietary supplement use the association with occasional use was as strong as that
with daily use, so dose might not be the relevant factor. This adds
to the health consciousness argument. Still, our results apply only
to the lung cancer patients, not the breast or colorectal cancer
patients. At study entry, 83.5% of the lung cancer patients were
current smokers and 12.6% former smokers, and at least not in
that sense having a healthy lifestyle.

Dietary supplement users and nonusers differ on several health

related variables.11,5056 In our sample, CLO users were more often never smokers. We tested a long list of covariates to adjust for
confounding variables, but only smoking and stage had a significant effect. Still we cannot rule out that there is some residual confounding. The tests for interaction between smoking and supplement use were negative, i.e. the effect of using CLO or other dietary supplements on mortality risk did not differ among smokers
and ex-smokers compared to never smokers.
This study has several strengths: the patients originated from a
nationally representative sample of Norwegian women, with cancer-rates closely mirroring those in the general population.29 The
participants answered several questions on CLO and other supplements, and a range of background variables was covered. A limitation is the lack of treatment information, and the limited number
of cases which did not allow for analyses by tumour histology or
cancer sub type. Due to the low number of cases in some categories of use the statistical power is limited, and the confidence intervals wide.
In conclusion, this study has shown that in lung cancer patients
taking dietary supplements before diagnosis was associated with
better survival. Whether this is due to beneficial effects of supplements, or differences between supplement users and nonusers cannot be determined. More research is needed to understand the
interplay between nutrients, whether in food or supplements and
cancer survival. Meanwhile, in countries where dietary supplement use is common, analyses of survival in cancer patients, particularly lung cancer patients, should take dietary supplement use
into account.
Acknowledgements
Guri Skeie was supported by EXTRA funds from the Norwegian Foundation for Health and Rehabilitation and the Norwegian
Cancer Society.

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