ArticlePublisher preview available

Distribution and determinants of retinol in Norwegian adolescents, and its relation to bone mineral density: the Tromsø Study: Fit Futures

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract and Figures

Background/objectives: Sufficient vitamin A levels are important for many functions-and both too little and too much may have detrimental health effects. The aim of the study was to describe the distribution of retinol levels in Norwegian adolescents, the relation between lifestyle factors and retinol levels, and the relation between retinol levels and bone mineral density (BMD). Subjects/methods: Serum retinol was measured in 414 girls and 474 boys aged 15-19 years, participating in the Tromsø Study: Fit Futures. Questionnaires regarding health and lifestyle factors were filled in, and physical examinations, body composition, and bone mineral density measurements (DEXA) performed. Multiple regression analyses were used to discover associations between retinol and exposure variables. Results: Retinol levels ranged from 0.26 to 6.46 μmol/L with a median (2.5-97.5 percentile) of 2.35 (1.01-4.67) μmol/L. There was no gender difference. In the multivariate models, fat mass, albumin level, physical activity, and lunch habits were positively associated with retinol levels in boys. In girls, fat mass and height were negatively associated with retinol levels, and lean mass, vitamin D, calcium, total cholesterol, and the use of contraceptives were positively associated with retinol levels (p < 0.05). The models explained 18.3% and 14.6% of the variation (R2) in girls and boys, respectively. Retinol levels were not independently associated with BMD. Conclusion: Retinol levels in Norwegian adolescents are higher than reported elsewhere, and are to a low degree explained by lifestyle and physical measurements. No independent association with BMD was found.
This content is subject to copyright. Terms and conditions apply.
European Journal of Clinical Nutrition (2018) 72:13731384
https://doi.org/10.1038/s41430-018-0193-z
ARTICLE
Clinical nutrition
Distribution and determinants of retinol in Norwegian adolescents,
and its relation to bone mineral density: the Tromsø Study: Fit
Futures
M. S. W. Teigmo1T. E. Gundersen2N. Emaus3G. Grimnes1
Received: 27 February 2018 / Revised: 13 April 2018 / Accepted: 24 April 2018 / Published online: 23 May 2018
© Macmillan Publishers Limited, part of Springer Nature 2018
Abstract
Background/objectives Sufcient vitamin A levels are important for many functionsand both too little and too much may
have detrimental health effects. The aim of the study was to describe the distribution of retinol levels in Norwegian
adolescents, the relation between lifestyle factors and retinol levels, and the relation between retinol levels and bone mineral
density (BMD).
Subjects/methods Serum retinol was measured in 414 girls and 474 boys aged 1519 years, participating in the Tromsø
Study: Fit Futures. Questionnaires regarding health and lifestyle factors were lled in, and physical examinations, body
composition, and bone mineral density measurements (DEXA) performed. Multiple regression analyses were used to
discover associations between retinol and exposure variables.
Results Retinol levels ranged from 0.26 to 6.46 μmol/L with a median (2.597.5 percentile) of 2.35 (1.014.67) μmol/L.
There was no gender difference. In the multivariate models, fat mass, albumin level, physical activity, and lunch habits were
positively associated with retinol levels in boys. In girls, fat mass and height were negatively associated with retinol levels,
and lean mass, vitamin D, calcium, total cholesterol, and the use of contraceptives were positively associated with retinol
levels (p< 0.05). The models explained 18.3% and 14.6% of the variation (R2) in girls and boys, respectively. Retinol levels
were not independently associated with BMD.
Conclusion Retinol levels in Norwegian adolescents are higher than reported elsewhere, and are to a low degree explained
by lifestyle and physical measurements. No independent association with BMD was found.
Introduction
Vitamin A plays an important role for vision, reproduction,
maintenance of epithelial surfaces and the immune system,
as well as for cell growth, differentiation, and death [1,2]. It
designates any compound possessing the biological activity
of retinol [1,3]. The term retinoidsincludes both natu-
rally occurring forms, such as carotenoids, retinyl ester, and
retinol, as well as synthetic analogs of retinol like
isotretinoin [24]. Provitamin-A carotenoids, which can be
converted into active vitamin A (retinol), are found in
colored fruits and vegetables, while active vitamin A (reti-
nol and retinyl ester) is found in animal tissues [13,5].
Retinyl esters are also present in margarine, cheese, and
breakfast cereals [1,5]. Vitamin A fortication of milk
occurs in some countries, but not in Norway [5,6]. Most of
the bodys total vitamin A is stored in the liver as retinyl
esters [4,7,8]. Symptoms of vitamin A deciency occur
when the storages are empty [9].
Vitamin A deciency is associated with increased risk of
infection, night blindness, and dryness of the eyes, which
can cause irreversible blindness [2], and increased mor-
bidity and mortality in children [9]. Vitamin A deciency is
a public health problem in more than 45 countries [2], but
not considered as a problem in developed countries like
Norway [9,10]. In a study among Norwegian adults, only
1.2% had serum retinol levels <0.70 mmol/L [10].
*M. S. W. Teigmo
maina.wergeland@gmail.com
1Tromsø Endocrine Research Group, Department of Clinical
Medicine, UiT The Arctic University of Norway, Tromsø, Norway
2Vitas AS, Oslo, Norway
3Department of Health and Care Sciences, UiT The Arctic
University of Norway, Tromsø, Norway
1234567890();,:
1234567890();,:
Content courtesy of Springer Nature, terms of use apply. Rights reserved
... For example, in a cross-sectional study of 426 children, Zhang et al. 36 found that vitamin A intake is positively related to BMD after adjusting confounders. However, in another study involving 888 subjects aged 15-19 years, Teigmo et al. 39 found no association between vitamin A status and BMD. Selenium is believed to play a role in bone health because of its antioxidant ability. ...
Article
Full-text available
Dietary antioxidants may have beneficial effects on bone health, but it remains uncertain in children and adolescents. This study investigates the association of composite dietary antioxidant index (CDAI) with bone mineral density (BMD) in children and adolescents aged 8–19 years from the National Health and Nutrition Examination Survey (NHANES) 2007–2010. The study assessed the relationship between CDAI and BMD in 2994 individuals aged 8–19 years (average age 13.48 ± 3.32 years) from the NHANES 2007–2010. Multivariate linear regression analyses were utilized to detect the association between CDAI and total spine, femur neck, and total femur BMD, adjusting for confounders including age, race/ethnicity, sex, poverty income ratio (PIR), body mass index (BMI), serum phosphorus and calcium. Stratified analyses and interaction tests were performed to examine the stability of the results. The weighted characteristics showed that subjects in the fourth CDAI quartile were more likely to be older, men, and Non-Hispanic White. They have higher values of serum total calcium and phosphorus. After adjusting all confounders, CDAI was positively associated with the total spine (β = 0.0031 95% CI 0.0021–0.0040), total femur (β = 0.0039 95% CI 0.0028–0.0049), and femur neck BMD (β = 0.0031 95% CI 0.0021–0.0040) in children and adolescents. Furthermore, we found no interaction effects between different race/ethnicity, age, and sex groups. Our findings suggest that dietary intake of multiple antioxidants was positively associated with BMD in children and adolescents. These findings provide valuable evidence for improving bone health in the early stages of life. However, more prospective studies are required to validate our findings and their causal relationship.
... To standardize the results according to the Vitamin D Standardization program (VSDP), stored samples were re-analysed at the Cork Centre for Vitamin D and Nutrition Research, Ireland [45]. More details are described elsewhere [46]. The standardized version of (25-OH)D (nmol/L) was used as a continuous variable. ...
Article
Full-text available
Background Inflammatory markers have been associated with depression and anxiety disorder in adolescents. Less is known about the association between inflammation and subclinical symptoms in the form of psychological distress. We investigated prevalence of psychological distress and examined the associations between common pro-inflammatory markers and psychological distress in an adolescent population sample. Methods The study was based on data from 458 girls and 473 boys aged 15–17 years from the Fit Futures Study, a large-scale study on adolescent health, conducted in Northern Norway. Psychological distress was measured with the Hopkins Symptom Checklist (HSCL-10). Serum-levels of the following low-grade inflammatory markers were measured: C-reactive protein (CRP), interleukin 6 (IL-6), transforming growth factor-alpha (TGF-α), tumor necrosis factor alpha variant 1 (TRANCE) and tumor necrosis factor alpha variant 2 (TWEAK). Associations between quartiles of inflammatory markers and HSCL-10 were examined by logistic regression and adjusted for potential confounders in sex-stratified analyses. Results The proportion of psychological distress above cutoff were 26.9% and 10.8% among girls and boys, respectively. In both girls and boys, crude analysis showed positive associations between all inflammatory markers and HSCL-10, except for TWEAK and TRANCE in boys. However, none of these associations were statistically significant. Further, there were no significant findings in the adjusted analyses. Conclusion There was a higher prevalence of psychological distress in girls compared to boys. Pro-inflammatory markers were not significantly associated with psychological distress in data from healthy adolescents aged 15–17 years.
... Stored samples were re-analyzed at the Cork Centre for Vitamin D and Nutrition Research, Ireland (Cashman et al., 2016) to be able to standardize the results according to the Vitamin D Standardization program (VSDP). More details are elaborated elsewhere (Teigmo et al., 2018). The standardized version of 25(OH)D (nmol/L) was used as a continuous variable. ...
Article
Full-text available
Objective The scarcity of research on associations between inflammatory markers and symptoms of depression and anxiety during adolescence has yielded inconsistent results. Further, not all studies have controlled for potential confounders. We explored the associations between baseline inflammatory markers and psychological distress including moderators at follow-up in a Norwegian adolescent population sample. Methods Data was derived from 373 girls and 294 boys aged 15–18 years at baseline, in the Fit Futures Study, a large-scale 2-year follow-up study on adolescent health. Baseline data was gathered from 2010 to 2011 and follow-up data from 2012 to 2013. Psychological distress was measured with Hopkins Symptom Checklist (HSCL-10). Serum levels of the following inflammatory markers were measured: C-reactive protein (CRP), Interleukin 6 (IL-6), Transforming growth factor alpha (TGF-α), Tumor necrosis factor alpha variant 1 (TRANCE), and variant 2 (TWEAK). Independent associations between baseline inflammatory markers and HSCL-10 at follow-up were explored by linear regressions, in sex-stratified analyses. Results In girls, analyses showed positive associations between all inflammatory markers and HSCL-10, except for TRANCE. However, all associations were non-significant in crude as well as in adjusted analyses. In boys, CRP (p = 0.03) and TGF-α (p < 0.01) showed significant associations with HSCL-10, that remained significant after adjustment. Additionally, moderators were found. In boys, CRP was associated with HSCL-10 in those with high body fat and those being physical inactive, and the association between TWEAK and HSCL-10 was dependent upon sleep duration. Conclusion There were significant prospective associations between CRP, TFG-α, and HSCL-10 in boys aged 15–18 years at baseline.
... Nevertheless, another study found opposite results: elevated serum retinol levels were associated with decreased BMD (38). One study reported that the level of serum retinol is not an independent factor affecting BMD (39). Recent studies have reported comparable findings with regard to the relationship between serum calcium and BMD. ...
Article
Purpose Multiple risk factors have been implicated in the development of osteoporosis. This study examined potential associations between serum nutritional factors and bone mineral density (BMD). Methods Six nutritional factors were selected as exposures. Outcomes included total body BMD (n = 66 945); BMD at the forearm (FA), femoral neck (FN) and lumbar spine (LS) (n = 8143, 32 735 and 28 498, respectively); estimated heel BMD (HL eBMD) (n = 394 929); and HL eBMD stratified by sex (n = 206 496). A two-sample Mendelian randomization (MR) approach was adopted to estimate the association between serum nutritional factors and BMD. The threshold for adjusted p-value was 1.39×10 -3. Results Serum calcium levels were inversely associated with LS BMD (effect = -0.55; 95% CI, -0.86 to -0.24; P = 0.001), whereas serum selenium levels were positively correlated with HL eBMD (effect = 0.22; 95% CI, 0.10 to 0.33; P = 1.70×10 -4). Regarding nominal significance, there was a positive association between serum selenium levels and FA BMD. Nominally significant results were also obtained for serum retinol as well as vitamin E levels and HL eBMD. Moreover, sex-specific effects of serum retinol and vitamin E levels on BMD were observed in men. Main Conclusions Serum calcium and selenium levels influence BMD at specific skeletal sites. This implies that these nutritional factors play crucial roles in bone metabolism.
Article
Full-text available
Background: Quantitative information on the conversion of beta-carotene to vitamin A in humans is limited. Objective: We determined the short- and long-term conversion of labeled beta-carotene to vitamin A by using a stable-isotope reference method. Design: [H-2(8)]beta-Carotene (11011 nmol, or 6 mg) in oil was given with a liquid diet (25% of energy from fat) to 22 adult volunteers (10 men, 12 women). Three days after the [H-2(8)]beta-carotene dose, the volunteers each took a dose of [H-2(8)]retinyl acetate (8915 nmol, or 3 mg) in oil with the same liquid diet. Blood samples were collected over 56 d. Results: The 53-d area under the serum (2)[H-4]retinol response curve (from the [H-2(8)]beta-carotene dose) was 569 +/- 385 nmol . d, and the 53-d area under the serum [H-2(8)]retinol response curve (from the [H-2(8)]retinyl acetate dose) was 1798 +/- 1139 nmol . d. With the use of [H-2(8)]retinyl acetate as the vitamin A reference, the [H-2(4)]retinol formed from [H-2(8)]beta-carotene (11011 nmol) was calculated to be equivalent to 3413.9 +/- 2298.4 nmol retinol. The conversion factor of beta-carotene to retinol varied from 2.4 to 20.2, and the average conversion factor was 9.1 to 1 by wt or 4.8 to 1 by mol. This conversion factor was positively correlated with body mass index (r = 0.57, P = 0.006). The postabsorption conversion of beta-carotene was estimated as 7.8%, 13.6%, 16.4%, and 19.0% of the total converted retinol at 6, 14, 21, or 53 d after the [H-2(8)]beta-carotene dose, respectively. Conclusion: The quantitative determination of the conversion of beta-carotene to vitamin A in humans can be accomplished by using a stable-isotope reference method. This approach provides in vivo metabolic information after a physiologic dose of beta-carotene.
Article
Full-text available
Background: Vitamin D deficiency has been described as being pandemic, but serum 25-hydroxyvitamin D [25(OH)D] distribution data for the European Union are of very variable quality. The NIH-led international Vitamin D Standardization Program (VDSP) has developed protocols for standardizing existing 25(OH)D values from national health/nutrition surveys. Objective: This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D deficiency in Europe. Design: The VDSP protocols were applied in 14 population studies [reanalysis of subsets of serum 25(OH)D in 11 studies and complete analysis of all samples from 3 studies that had not previously measured it] by using certified liquid chromatography-tandem mass spectrometry on biobanked sera. These data were combined with standardized serum 25(OH)D data from 4 previously standardized studies (for a total n = 55,844). Prevalence estimates of vitamin D deficiency [using various serum 25(OH)D thresholds] were generated on the basis of standardized 25(OH)D data. Results: An overall pooled estimate, irrespective of age group, ethnic mix, and latitude of study populations, showed that 13.0% of the 55,844 European individuals had serum 25(OH)D concentrations <30 nmol/L on average in the year, with 17.7% and 8.3% in those sampled during the extended winter (October-March) and summer (April-November) periods, respectively. According to an alternate suggested definition of vitamin D deficiency (<50 nmol/L), the prevalence was 40.4%. Dark-skinned ethnic subgroups had much higher (3- to 71-fold) prevalence of serum 25(OH)D <30 nmol/L than did white populations. Conclusions: Vitamin D deficiency is evident throughout the European population at prevalence rates that are concerning and that require action from a public health perspective. What direction these strategies take will depend on European policy but should aim to ensure vitamin D intakes that are protective against vitamin D deficiency in the majority of the European population.
Article
Full-text available
Aim: The aim was to study vitamin D status in a healthy adolescent Norwegian population at 69°N. Methods: The data presented come from The Tromsø Study: Fit Futures, during the school year 2010/2011 (not including the summer months), where 1,038 (92% of those invited) participated. Physical examinations, questionnaires and blood samples were collected, and serum 25-hydroxyvitamin D (25(OH)D) were analyzed using LC-MS/MS. Results: RESULTS are presented from 475 boys and 415 girls (15-18 years old) with available blood samples. A total of 60.2% had vitamin D deficiency or insufficiency (serum 25(OH)D <50 nmol/l), 16.5% were deficient (<25 nmol/l) and 1.6% had severe vitamin D deficiency (<12.5 nmol/l). Only 12.4% had levels >75 nmol/l. A significant gender difference with a mean (SD) serum 25(OH)D level of 40.5 (20.5) nmol/l in boys and 54.2 (23.2) nmol/l in girls (p <0.01) was present. Furthermore, 51.3% of girls had levels >50 nmol/l in comparison to 29.7% of boys (p <0.01). There was an inverse correlation between parathyroid hormone levels and 25(OH)D, rs= -0.30 (p<0.01). Explanatory factors that were significantly associated with serum 25(OH)D levels in multivariate models were use of snuff, consumption of vitamin D fortified milk, cod liver oil and vitamin/mineral supplements, physical activity, sunbathing holiday and use of solarium in boys, and vitamin/mineral supplements, physical activity, sunbathing holiday and use of solarium in girls . Conclusions: Vitamin D deficiency is prevalent during the school year among adolescents in northern Norway, particularly among boys.
Article
Full-text available
In acne vulgaris, antimicrobial peptides (AMPs) could play a dual role; i.e., protective by acting against Propionibacterium acnes, pro-inflammatory by acting as signalling molecules. The cutaneous expression of 15 different AMPs was investigated in acne patients; furthermore, the impact of isotretinoin therapy on AMP expression was analysed in skin biopsies from 13 patients with acne vulgaris taken before, during and after a 6-month treatment cycle with isotretinoin using quantitative real-time polymerase chain reaction. Cutaneous expression of the AMPs cathelicidin, human β-defensin-2 (HBD-2), lactoferrin, lysozyme, psoriasin (S100A7), koebnerisin (S100A15), and RNase 7 was upregulated in untreated acne vulgaris, whereas α-defensin-1 (HNP-1) was downregulated compared to controls. While relative expression levels of cathelicidin, HBD-2, lactoferrin, psoriasin (S100A7), and koebnerisin (S100A15) decreased during isotretinoin treatment, only those of cathelicidin and koebnerisin returned to normal after 6 months of isotretinoin therapy. The increased expression of lysozyme and RNase 7 remained unaffected by isotretinoin treatment. The levels of granulysin, RANTES (CCL5), perforin, CXCL9, substance P, chromogranin B, and dermcidin were not regulated in untreated acne patients and isotretinoin had no effect on these AMPs. In conclusion, the expression of various AMPs is altered in acne vulgaris. Isotretinoin therapy normalizes the cutaneous production of distinct AMPs while the expression of others is still increased in healing acne. Considering the antimicrobial and pro-inflammatory role of AMPs, these molecules could serve as specific targets for acne therapy and maintenance of clinical remission.
Article
The purpose of this study was to investigate the status of retinol, beta-carotene, and alpha-tocopherol serum concentrations in adolescents with dyslipidemia. A case series dyslipidemia study was conducted, with an attached control group, including 104 adolescents of public schools in Recife during the months of March/April 2013. Retinol, beta-carotene and alpha-tocopherol serum concentrations were analysed by high efficiency liquid chromatography. Sociodemographic, anthropometric, clinical and biochemical variables were analysed. Dyslipidemic adolescents had high serum concentrations of both retinol (p=0.007) and beta-carotene/apolipoprotein A-I ratio (p=0.034); they also had low concentrations of beta-carotene/total cholesterol (p<0.0001) and beta-carotene/apolipoprotein B ratios (p=0.033) when compared to the controls. The alpha-tocopherol serum status was not associated with dyslipidemia. Overweight, abdominal obesity, lipid profile markers, and systolic and diastolic blood pressures were more prevalent in dyslipidemic adolescents. The findings show an association between vitamin A and dyslipidemia in adolescents. However, additional investigations of this risk group are necessary to clarify the mechanisms of action of this nutrient in the pathogenesis of this syndrome, aiming at reducing cardiometabolic risks as of earlier ages.
Article
Background: Norway has the highest hip fracture rates worldwide and a relatively high vitamin A intake. Increased fracture risk at high intakes and serum concentrations of retinol (s-retinol) have been observed in epidemiologic studies. Objective: We aimed to study the association between s-retinol and hip fracture and whether high s-retinol may counteract a preventive effect of vitamin D. Design: We conducted the largest prospective analysis of serum retinol and hip fracture to date in 21,774 men and women aged 65-79 y (mean age 72 y) who attended 4 community-based health studies during 1994-2001. Incident hip fractures occurring up to 10.7 y after baseline were retrieved from electronic hospital discharge registers. Retinol determined by high-pressure liquid chromatography with ultraviolet detection in stored serum was available in 1154 incident hip fracture cases with valid body mass index (BMI) data and in a subcohort defined as a sex-stratified random sample (n = 1418). Cox proportional hazards regression weighted according to the stratified case-cohort design was performed. Results: There was a modest increased risk of hip fracture in the lowest compared with the middle quintile of s-retinol (HR: 1.41; 95% CI: 1.09, 1.82) adjusted for sex and study center. The association was attenuated after adjustment for BMI and serum concentrations of α-tocopherol (HR: 1.16; 95% CI: 0.88, 1.51). We found no increased risk in the upper compared with the middle quintile. No significant interaction between serum concentrations of 25-hydroxyvitamin D and s-retinol on hip fracture was observed (P = 0.68). Conclusions: We found no evidence of an adverse effect of high serum retinol on hip fracture or any interaction between retinol and 25-hydroxyvitamin D. If anything, there tended to be an increased risk at low retinol concentrations, which was attenuated after control for confounders. We propose that cod liver oil, a commonly used food supplement in Norway, should not be discouraged as a natural source of vitamin D for fracture prevention.
Article
Background: The highest incidence of osteoporotic fractures is found in northern Europe, where dietary intake of vitamin A (retinol) is unusually high. In animals, the most common adverse effect of toxic doses of retinol is spontaneous fracture. Objective: To investigate whether excessive dietary intake of vitamin A is associated with decreased bone mineral density and increased risk for hip fracture. Design: A cross-sectional study and a nested case-control study. Setting: Two counties in central Sweden. Participants: For the cross-sectional study, 175 women 28 to 74 years of age were randomly selected. For the nested case-control study, 247 women who had a first hip fracture within 2 to 64 months after enrollment and 873 age-matched controls were selected from a mammography study cohort of 66 651 women 40 to 76 years of age. Measurements: Retinol intake was estimated from dietary records and a food-frequency questionnaire. Bone mineral density was measured with dual-energy x-ray absorptiometry. Hip fracture was identified by using hospital discharge records and was confirmed by record review. Results: In multivariate analysis, retinol intake was negatively associated with bone mineral density. For every 1-mg increase in daily intake of retinol, risk for hip fracture increased by 68% (95% Cl, 18% to 140%; P for trend, 0.006). For intake greater than 1.5 mg/d compared with intake less than 0.5 mg/d, bone mineral density was reduced by 10% at the femoral neck (P = 0.05), 14% at the lumbar spine (P = 0.001), and 6% for the total body (P = 0.009) and risk for hip fracture was doubled (odds ratio, 2.1 [Cl, 1.1 to 4.0]). Conclusion: High dietary intake of retinol seems to be associated with osteoporosis.
Article
Background and Aims Although studies have suggested that vitamin A is associated with cardiovascular events and mortality, it remains unclear whether low doses or high doses of vitamin A have harmful effects on the cardiovascular system. This study investigated whether serum vitamin A levels are associated with all-cause and cause-specific mortality in US older adults. Methods and Results We analyzed the mortality information for 6069 participants aged 50 years or older who had serum vitamin A data available from the baseline examination. The participants were categorized as having deficient (<30 μg/dL), normal (30-80 μg/dL), or excessive (>80 μg/dL) levels of serum vitamin A, and a multivariate Cox proportional hazards regression analysis was performed on mortality. We found a U-shaped association between serum vitamin A levels and death from all-cause and cause-specific mortality among US adults. Comparing the normal range of serum vitamin A, the hazard ratio with deficient serum vitamin A was 2.9 (95% CI 2.0-4.3) for all-cause mortality, 2.1 (95% CI 1.1-4.1) for cardiovascular-related mortality and 2.5 (95% CI 1.2-5.3) for coronary artery disease–related mortality. Excessive serum vitamin A was associated with a 1.2-fold (95% CI 1.1-1.4) increased risk of all-cause mortality, a 1.4-fold (95% CI 1.2-1.8) increased risk of cardiovascular-related mortality, and a 1.5-fold (95% CI 1.2-2.0) increased risk of coronary artery disease–related mortality compared with the reference group. Conclusion The finding suggests that serum vitamin A levels less than 30 μg/dL or greater than 80 μg/dL levels may indicate a high risk of subsequent mortality.