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Higher intake of cryptoxanthin is related to low body mass index and body fat in Japanese middle-aged women

Open AccessPublished:November 16, 2016DOI:https://doi.org/10.1016/j.maturitas.2016.11.008

      Highlights

      • Nutrients that affect body mass index and body fat in middle-aged women were investigated.
      • Ninety-eight nutritional factors were assessed using a diet history questionnaire.
      • Higher intake of cryptoxanthin was shown to be associated with a low body mass index and low amounts of body fat.

      Abstract

      Objectives

      The prevalence of cardiovascular diseases increases with age, especially in postmenopausal women. In this study, we investigated the dietary patterns associated with body mass and body fat in Japanese middle-aged women.

      Study design

      Cross-sectional.

      Main outcome measures

      This study used baseline data collected in a previous study in 88 women aged 40–60 years. Participants were assessed for age, menopausal status, lifestyle factors, body composition, and dietary habits using a brief-type self-administered diet history questionnaire, which provides information on the amounts of nearly 100 nutritional factors consumed during the previous month. Classifying body mass index (BMI) as low (≤22 kg/m2) or high (>22 kg/m2) and percentage body fat as low (≤25%) or high (>25%), we sought to identify the nutritional factors associated with BMI and percentage body fat.

      Results

      Consumption differences between high/low BMI and high/low body fat percentage groups were not significant for any nutritional factors except cryptoxanthin. Multiple logistic regression analysis adjusting for age, menopausal status, working, exercise, and smoking revealed that higher cryptoxanthin intake was associated with low BMI (adjusted odds ratio, 1.22 per 100 μg/day increase of cryptoxanthin intake; 95% confidence interval, 1.01–1.52) and low body fat percentage (adjusted odds ratio, 1.36 per 100 μg/day increase of cryptoxanthin intake; 95% confidence interval, 1.13–1.70).

      Conclusions

      Higher intake of cryptoxanthin was shown to be related to low body mass and body fat in Japanese middle-aged women.

      Abbreviations:

      ABC (ATP-binding cassette transporter), BDHQ (brief-type self-administered diet history questionnaire), BMI (body mass index), PPAR (peroxisome proliferator-activated receptor), RAR (retinoic acid receptor), RXR (retinoid X receptor)

      Keywords

      1. Introduction

      The prevalence of cardiovascular diseases increases with age, especially after menopause in women [
      • Carr M.C.
      The emergence of the metabolic syndrome with menopause.
      ,
      • Rosano G.M.
      • Vitale C.
      • Tulli A.
      Managing cardiovascular risk in menopausal women.
      ,
      • Lizcano F.
      • Guzmán G.
      Estrogen deficiency and the origin of obesity during menopause.
      ,
      • Collins P.
      • Rosano G.
      • Casey C.
      • Daly C.
      • Gambacciani M.
      • Hadji P.
      • Kaaja R.
      • Mikkola T.
      • Palacios S.
      • Preston R.
      • Simon T.
      • Stevenson J.
      • Stramba-Badiale M.
      Management of cardiovascular risk in the peri-menopausal woman: a consensus statement of European cardiologists and gynaecologists.
      ]. The postmenopausal increase in cardiovascular risk factors, such as central obesity, hypertension, dyslipidemia, and diabetes is not only caused by unhealthy diets, physical inactivity, smoking, and harmful use of alcohol, but also partly explained by estrogen withdrawal [
      • Rosano G.M.
      • Vitale C.
      • Marazzi G.
      • Volterrani M.
      Menopause and cardiovascular disease: the evidence.
      ]. Menopausal transition is thought to be associated with weight gain [
      • Macdonald H.M.
      • New S.A.
      • Campbell M.K.
      • Reid D.M.
      Longitudinal changes in weight in perimenopausal and early postmenopausal women: effects of dietary energy intake, energy expenditure, dietary calcium intake and hormone replacement therapy.
      ], as exemplified by a study revealing that middle-aged women gained an average of 2.25 ± 4.19 kg during a 3-year menopausal period [
      • Wing R.R.
      • Matthews K.A.
      • Kuller L.H.
      • Meilahn E.N.
      • Plantinga P.L.
      Weight gain at the time of menopause.
      ]. The types of nutrients as well as total calories consumed may affect body composition, including body mass and body fat. A number of dietary habits, such as high-fat [
      • Golay A.
      • Bobbioni E.
      The role of dietary fat in obesity.
      ], low-carbohydrate [
      • Kreider R.B.
      • Rasmussen C.
      • Kerksick C.M.
      • Wilborn C.
      • Taylor L.
      • Campbell B.
      • Magrans-Courtney T.
      • Fogt D.
      • Ferreira M.
      • Li R.
      • Galbreath M.
      • Iosia M.
      • Cooke M.
      • Serra M.
      • Gutierrez J.
      • Byrd M.
      • Kresta J.Y.
      • Simbo S.
      • Oliver J.
      • Greenwood M.
      A carbohydrate-restricted diet during resistance training promotes more favorable changes in body composition and markers of health in obese women with and without insulin resistance.
      ], and high-sugar foods [
      • Trumbo P.R.
      • Rivers C.R.
      Systematic review of the evidence for an association between sugar-sweetened beverage consumption and risk of obesity.
      ] and low intake of calcium [
      • Soares M.J.
      • Murhadi L.L.
      • Kurpad A.V.
      • Chan She Ping-Delfos W.L.
      • Piers L.S.
      Mechanistic roles for calcium and vitamin D in the regulation of body weight.
      ], vitamins [
      • Soares M.J.
      • Murhadi L.L.
      • Kurpad A.V.
      • Chan She Ping-Delfos W.L.
      • Piers L.S.
      Mechanistic roles for calcium and vitamin D in the regulation of body weight.
      ,
      • Li Y.
      • Wang C.
      • Zhu K.
      • Feng R.N.
      • Sun C.H.
      Effects of multivitamin and mineral supplementation on adiposity, energy expenditure and lipid profiles in obese Chinese women.
      ], and minerals [
      • Li Y.
      • Wang C.
      • Zhu K.
      • Feng R.N.
      • Sun C.H.
      Effects of multivitamin and mineral supplementation on adiposity, energy expenditure and lipid profiles in obese Chinese women.
      ] have been suggested to associate with high body mass and body fat in previous studies. However, the precise nutritional factors that directly affect body composition remain to be elucidated.
      The aim of this study was to investigate nutritional factors that are independently associated with body composition, especially body mass index (BMI) and body fat percentage, in Japanese middle-aged women.

      2. Methods

      2.1 Study population

      In the present study, we performed a cross-sectional analysis using the baseline data of a previous study conducted at the Menopause Clinic of the Tokyo Medical and Dental University that examined the effects of a dietary supplement on a variety of health parameters in 88 Japanese women [
      • Terauchi M.
      • Horiguchi N.
      • Kajiyama A.
      • Akiyoshi M.
      • Owa Y.
      • Kato K.
      • Kubota T.
      Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized double-blind, placebo-controlled pilot study.
      ]. The inclusion criteria were those who aged between 40 and 60 and having at least one menopausal symptom on the Menopausal Health-Related Quality of Life (MHR-QOL) Questionnaire (score >1). The exclusion criteria were those who were receiving menopausal hormone therapy, herbal medicine, or psychotropic drugs. The participants were recruited through advertisements posted in our hospital and in the patients’ social network. Collected information included: age; menopausal status; lifestyle factors such as working, exercise, and smoking; body composition; and detailed dietary habits. The study protocol was reviewed and approved by the Tokyo Medical and Dental University Review Board, and written informed consent was obtained from all participants. The study was conducted in accordance with the Declaration of Helsinki.
      Participants’ menopausal status was classified as follows: premenopausal (regular menstrual cycles in the past 3 months), perimenopausal (a menstrual period within the past 12 months but a missed period or irregular cycles in the past 3 months), postmenopausal (no menstrual period in the past 12 months), or surgically induced menopause (hysterectomy).

      2.2 Measures

      2.2.1 Body composition and cardiovascular parameters

      Participants’ body composition, including height, weight, BMI, fat mass, and muscle mass, was assessed using a body composition analyzer (MC190-EM; Tanita, Tokyo, Japan).

      2.2.2 Dietary habits

      Dietary habits were assessed using a brief-type self-administered diet history questionnaire (BDHQ), a short version of a self-administered diet history questionnaire that was developed in Japan [
      • Sasaki S.
      • Yanagibori R.
      • Amano K.
      Self-administered diet history questionnaire developed for health education: a relative validation of the test-version by comparison with 3-day diet record in women.
      ]. The BDHQ asks about the consumption frequency of selected food and beverage items commonly consumed in Japan, mainly from the food list used in the National Health and Nutrition Survey of Japan [
      • Okubo H.
      • Sasaki S.
      • Rafamantanantsoa H.H.
      • Ishikawa-Takata K.
      • Okazaki H.
      • Tabata I.
      Validation of self-reported energy intake by a self-administered diet history questionnaire using the doubly labeled water method in 140 Japanese adults.
      ,
      • Kobayashi S.
      • Honda S.
      • Murakami K.
      • Sasaki S.
      • Okubo H.
      • Hirota N.
      • Notsu A.
      • Fukui M.
      • Date C.
      Both comprehensive and brief self-administered diet history questionnaires satisfactorily rank nutrient intakes in Japanese adults.
      ]. Based on the information provided responses to the BDHQ, an ad hoc computer algorithm estimated the amounts of 98 nutritional factors consumed during the previous month [
      • Okubo H.
      • Sasaki S.
      • Rafamantanantsoa H.H.
      • Ishikawa-Takata K.
      • Okazaki H.
      • Tabata I.
      Validation of self-reported energy intake by a self-administered diet history questionnaire using the doubly labeled water method in 140 Japanese adults.
      ,
      • Kobayashi S.
      • Murakami K.
      • Sasaki S.
      • Okubo H.
      • Hirota N.
      • Notsu A.
      • Fukui M.
      • Date C.
      Comparison of relative validity of food group intakes estimated by comprehensive and brief-type self-administered diet history questionnaires against 16 d dietary records in Japanese adults.
      ]. Table 1 shows the major nutritional factors listed on the BDHQ.
      Table 1Major nutritional factors assessed with BDHQ.
      EnergyCopperCholesterol
      Weight of foodsManganeseSoluble dietary fiber
      WaterRetinolInsoluble dietary fiber
      ProteinVitamin DDietary fiber
      Animal proteinα-TocopherolSalt equivalent
      Vegetable proteinVitamin KSucrose
      FatVitamin B1Alcohol
      Animal fatVitamin B2Daidzein
      Vegetable fatNiacinGenistein
      CarbohydrateVitamin B6n-3 fatty acid
      Ash contentVitamin B12n-6 fatty acid
      SodiumFolic acidα-Carotene
      PotassiumPantothenic acidβ-Carotene
      CalciumVitamin CCryptoxanthin
      MagnesiumSaturated fatty acidβ-Tocopherol
      PhosphorusMonounsaturated fatty acidγ-Tocopherol
      IronPolyunsaturated fatty acidδ-Tocopherol
      Zinc
      BDHQ, brief-type self-administered diet history questionnaire.

      2.3 Statistical analyses

      We classified body mass index (BMI) level as low (≤22 kg/m2) and high (>22 kg/m2) according to the Japan Society for the Study of Obesity, and body fat percentage level as low (≤25%) and high (>25%) according to the Ministry of Health, Labour and Welfare. First, all nutrients were compared between the low and high BMI/body fat percentage groups using univariate analyses (unpaired t-test) in order to determine the association between body composition and the dietary intake of each nutritional factor. Variables emerging with possible prognostic value for low BMI and body fat percentage (P < 0.05) were then entered into a multiple logistic regression analysis (Model 1). We examined the association adjusting for age and menopausal status (Model 2), and for age, menopausal status, working, exercise, and smoking (Model 3). The variables that remained significant (P < 0.05) were retained in the final multivariate model and considered to be associated with the level of BMI and body fat percentage in Japanese middle-aged women. Statistical analyses were performed using GraphPad Prism version 5.02 (GraphPad Software, San Diego, CA, USA) and JMP version 11.0.0 (SAS Institute Inc, Cary, NC, USA).

      3. Results

      The characteristics of 88 middle-aged women enrolled in the study are shown in Table 2. The participants were divided into two groups according to the level of BMI and body fat percentage: 56 women were classified as having low BMI (≤22 kg/m2) and 32 women as high BMI (>22 kg/m2). Thirty-five women were classified as having low body fat percentage levels (≤25%), and 53 women as having high levels (>25%).
      Table 2Background characteristics of the participants (N = 88).
      MeanSDNumber%
      Age, y49.75.0
      Gravida0.590.49
      Para0.560.50
      Menopausal status,
       premenopausal

       perimenopausal

       postmenopausal

       surgically induced
      38

      17

      26

      7
      43.2

      19.3

      9.5

      8.0
      Height, cm156.75.1
      Weight, kg52.66.9
      Body mass index, kg/cm221.42.7
      Body fat percentage, %26.36.6
      Lean body mass, kg38.42.8
      Muscle amount, kg36.22.5
      Resting energy expenditure, kcal/day1818.3442.1
      Body temperature, °C36.30.46
      Waist-to-hip ratio0.850.07
      Working, (yes/no)79/989.8/10.2
      Regularly exercising, (yes/no)40/4845.5/54.5
      Smoking, (yes/no)10/7811.4/88.6
      We first compared the estimated daily intake of each nutrient between the low and high BMI and body fat percentage groups using unpaired t-test. The women with low BMI level consumed significantly more cryptoxanthin (4.1 ± 2.9 vs. 2.9 ± 2.2 mg/day, mean ± SD, P = 0.048) (Table 3). Likewise, those with low body fat percentage consumed significantly more cryptoxanthin (4.8 ± 3.1 vs. 2.9 ± 2.1 mg/day, mean ± SD, P = 0.001) (Table 4). The other 97 nutritional factors showed no significant difference in daily consumption between the groups.
      Table 3Comparison of daily intake of nutritional factors between the low and high BMI groups using univariate analysis.
      Low BMI

      (≤22 kg/cm2, N = 56)
      High BMI

      (>22 kg/cm2, N = 32)
      P value
      MeanSDMeanSD
      Age, y49.35.150.54.80.26
      Unpaired t-test.
      Gravida0.590.490.590.490.97
      Unpaired t-test.
      Para0.520.500.630.480.34
      Unpaired t-test.
      Menopausal status, %
       premenopausal

       perimenopausal

       postmenopausal

       surgically induced
      48.2

      16.1

      28.6

      7.1
      34.4

      25.0

      31.3

      9.4
      0.59
      Chi-square test.
      Working (yes/no), %59.3/10.790.6/9.41.00
      Chi-square test.
      Regularly exercising (yes/no), %51.8/48.234.4/65.60.13
      Chi-square test.
      Smoking (yes/no), %12.5/87.59.4/90.60.74
      Chi-square test.
      Height, cm157.54.9155.35.10.053
      Unpaired t-test.
      Weight, kg49.14.858.75.6<0.0001
      Unpaired t-test.
      Body fat percentage, %22.54.633.03.7<0.0001
      Unpaired t-test.
      Lean body mass, kg37.92.739.22.70.31
      Unpaired t-test.
      Muscle amount, kg35.72.536.92.40.31
      Unpaired t-test.
      Resting energy expenditure, kcal/day1794.4373.01860.0539.70.51
      Unpaired t-test.
      Body temperature, °C36.30.4536.10.440.036
      Unpaired t-test.
      Waist-to-hip ratio0.830.0700.900.060<0.0001
      Unpaired t-test.
      Energy, kcal1651.2588.81720.2407.60.56
      Unpaired t-test.
      Weight of foods, g2191.3720.02233.4478.80.77
      Unpaired t-test.
      Water, g1831.2595.11860.1430.00.81
      Unpaired t-test.
      Protein, g64.923.065.420.70.91
      Unpaired t-test.
      Animal protein, g36.213.836.717.10.88
      Unpaired t-test.
      Vegetable protein, g28.714.628.78.70.99
      Unpaired t-test.
      Fat, g50.618.552.217.30.69
      Unpaired t-test.
      Animal fat, g22.28.422.010.30.93
      Unpaired t-test.
      Vegetable fat, g28.412.330.210.20.48
      Unpaired t-test.
      Carbohydrate, g218.098.7227.261.20.64
      Unpaired t-test.
      Ash content, g17.66.017.84.50.83
      Unpaired t-test.
      Sodium, mg3725.11021.03973.01037.00.28
      Unpaired t-test.
      Potassium, mg2770.11329.42638.6831.80.62
      Unpaired t-test.
      Calcium, mg546.6264.6506.0174.00.44
      Unpaired t-test.
      Magnesium, mg255.4112.1246.971.50.70
      Unpaired t-test.
      Phosphorus, mg996.2383.3982.6275.10.86
      Unpaired t-test.
      Iron, mg7.93.67.72.60.87
      Unpaired t-test.
      Zinc, mg7.52.77.82.50.64
      Unpaired t-test.
      Copper, mg1.10.51.10.40.94
      Unpaired t-test.
      Manganese, mg3.11.33.21.10.53
      Unpaired t-test.
      Retinol, μg378.1388.8431.9311.10.51
      Unpaired t-test.
      Vitamin D, μg11.16.910.15.40.48
      Unpaired t-test.
      α-Tocopherol, mg7.63.27.42.40.79
      Unpaired t-test.
      Vitamin K, μg344.7232.8316.0149.30.54
      Unpaired t-test.
      Vitamin B1, mg0.790.330.780.260.87
      Unpaired t-test.
      Vitamin B2, mg1.30.51.30.40.79
      Unpaired t-test.
      Niacin, mg17.05.717.35.70.84
      Unpaired t-test.
      Vitamin B6, mg1.30.61.30.40.95
      Unpaired t-test.
      Vitamin B12, μg7.74.17.94.30.81
      Unpaired t-test.
      Folic acid, μg372.8199.4361.9134.10.79
      Unpaired t-test.
      Pantothenic acid, mg6.32.66.21.90.83
      Unpaired t-test.
      Vitamin C, mg137.784.6128.657.30.60
      Unpaired t-test.
      Saturated fatty acid, g13.75.914.04.60.77
      Unpaired t-test.
      Monounsaturated fatty acid, g18.06.519.07.20.52
      Unpaired t-test.
      Polyunsaturated fatty acid, g12.14.212.54.30.72
      Unpaired t-test.
      Cholesterol, mg342.9151.2336.5139.10.85
      Unpaired t-test.
      Soluble dietary fiber, g3.52.23.41.50.92
      Unpaired t-test.
      Insoluble dietary fiber, g9.45.69.23.60.87
      Unpaired t-test.
      Dietary fiber, g13.38.112.95.20.83
      Unpaired t-test.
      Salt equivalent, g9.42.610.02.60.28
      Unpaired t-test.
      Sucrose, g15.612.915.58.20.98
      Unpaired t-test.
      Alcohol, g7.713.49.218.50.66
      Unpaired t-test.
      Daidzein, mg13.511.211.58.10.38
      Unpaired t-test.
      Genistein, mg23.019.019.613.70.38
      Unpaired t-test.
      n-3 Fatty acid, g2.41.02.30.80.83
      Unpaired t-test.
      n-6 Fatty acid, g9.73.410.13.50.61
      Unpaired t-test.
      α-Carotene, μg508.8429.4508.1316.20.99
      Unpaired t-test.
      β-Carotene, μg4237.13242.63861.91836.30.55
      Unpaired t-test.
      Cryptoxanthin, 102 × μg4.12.92.92.2<0.05
      Unpaired t-test.
      β-Tocopherol, mg0.350.140.370.110.54
      Unpaired t-test.
      γ-Tocopherol, mg12.14.512.64.70.67
      Unpaired t-test.
      δ-Tocopherol, mg3.11.43.11.20.98
      Unpaired t-test.
      a Unpaired t-test.
      b Chi-square test.
      Table 4Comparison of daily intake of nutritional factors between the low and high body fat percentage groups using univariate analysis.
      Low body fat percentage

      (≤25%, N = 35)
      High body fat percentage

      (>25%, N = 53)
      P value
      MeanSDMeanSD
      Age, y49.85.149.75.00.91
      Unpaired t-test.
      Gravida0.570.500.600.490.77
      Unpaired t-test.
      Para0.510.500.590.490.52
      Unpaired t-test.
      Menopausal status, %
       premenopausal

       perimenopausal

       postmenopausal

       surgically induced
      54.3

      17.1

      25.7

      2.9
      35.8

      20.8

      32.1

      11.3
      0.26
      Chi-square test.
      Working (yes/no), %91.4/8.688.7/11.31.0
      Chi-square test.
      Regularly exercising (yes/no), %54.3/45.739.6/60.40.20
      Chi-square test.
      Smoking (yes/no), %14.3/85.79.4/90.60.51
      Chi-square test.
      Height, cm157.05.2156.55.10.67
      Unpaired t-test.
      Weight, kg47.14.556.25.7<0.0001
      Unpaired t-test.
      Body mass index, kg/cm219.11.423.02.2<0.0001
      Unpaired t-test.
      Lean body mass, kg37.62.938.92.60.027
      Unpaired t-test.
      Muscle amount, kg35.42.636.72.40.027
      Unpaired t-test.
      Resting energy expenditure, kcal/day1746.6342.41865.6491.50.22
      Unpaired t-test.
      Body temperature, °C36.30.4536.20.460.18
      Unpaired t-test.
      Waist-to-hip ratio0.820.0750.880.061<0.0001
      Unpaired t-test.
      Energy, kcal1728.1632.51642.1448.70.46
      Unpaired t-test.
      Weight of foods, g2253.4814.72175.7496.10.58
      Unpaired t-test.
      Water, g1875.4676.71819.4427.30.64
      Unpaired t-test.
      Protein, g66.224.564.320.60.70
      Unpaired t-test.
      Animal protein, g35.914.336.615.60.83
      Unpaired t-test.
      Vegetable protein, g30.316.727.79.10.35
      Unpaired t-test.
      Fat, g52.118.150.618.10.72
      Unpaired t-test.
      Animal fat, g22.38.422.059.60.89
      Unpaired t-test.
      Vegetable fat, g29.711.828.611.40.65
      Unpaired t-test.
      Carbohydrate, g232.1110.8214.266.00.35
      Unpaired t-test.
      Ash content, g17.96.817.54.50.71
      Unpaired t-test.
      Sodium, mg3752.61082.63856.6998.10.65
      Unpaired t-test.
      Potassium, mg2899.51548.82605.2820.30.26
      Unpaired t-test.
      Calcium, mg557.9298.8514.7182.10.41
      Unpaired t-test.
      Magnesium, mg265.1130.7243.970.20.33
      Unpaired t-test.
      Phosphorus, mg1020.8423.1971.7286.20.52
      Unpaired t-test.
      Iron, mg8.04.07.72.60.65
      Unpaired t-test.
      Zinc, mg7.72.97.62.40.84
      Unpaired t-test.
      Copper, mg1.10.61.10.30.51
      Unpaired t-test.
      Manganese, mg3.11.43.11.00.88
      Unpaired t-test.
      Retinol, μg378.7241.8410.2424.60.70
      Unpaired t-test.
      Vitamin D, μg11.07.410.55.70.72
      Unpaired t-test.
      α-Tocopherol, mg7.93.47.32.50.32
      Unpaired t-test.
      Vitamin K, μg357.6269.8318.9149.70.40
      Unpaired t-test.
      Vitamin B1, mg0.830.360.760.250.36
      Unpaired t-test.
      Vitamin B2, mg1.30.51.30.40.77
      Unpaired t-test.
      Niacin, mg17.66.316.85.30.55
      Unpaired t-test.
      Vitamin B6, mg1.30.61.20.40.40
      Unpaired t-test.
      Vitamin B12, μg7.64.07.94.20.76
      Unpaired t-test.
      Folic acid, μg387.3230.0356.6132.80.44
      Unpaired t-test.
      Pantothenic acid, mg6.62.96.11.90.33
      Unpaired t-test.
      Vitamin C, mg148.699.1125.053.60.16
      Unpaired t-test.
      Saturated fatty acid, g13.95.513.75.40.87
      Unpaired t-test.
      Monounsaturated fatty acid, g18.66.118.27.20.81
      Unpaired t-test.
      Polyunsaturated fatty acid, g12.54.412.04.10.60
      Unpaired t-test.
      Cholesterol, mg344.5149.5338.0145.20.84
      Unpaired t-test.
      Soluble dietary fiber, g3.72.63.31.40.28
      Unpaired t-test.
      Insoluble dietary fiber, g10.06.68.93.30.30
      Unpaired t-test.
      Dietary fiber, g14.29.612.54.90.28
      Unpaired t-test.
      Salt equivalent, g9.52.79.72.50.65
      Unpaired t-test.
      Sucrose, g16.212.615.110.50.67
      Unpaired t-test.
      Alcohol, g8.113.38.316.70.96
      Unpaired t-test.
      Daidzein, mg13.812.912.28.00.47
      Unpaired t-test.
      Genistein, mg23.521.920.713.40.46
      Unpaired t-test.
      n-3 Fatty acid, g2.51.12.30.80.38
      Unpaired t-test.
      n-6 Fatty acid, g10.03.59.73.40.69
      Unpaired t-test.
      α-Carotene, μg570.5501.2467.6291.70.23
      Unpaired t-test.
      β-Carotene, μg4579.33647.53784.52040.20.20
      Unpaired t-test.
      Cryptoxanthin, 102 × μg4.83.12.92.1<0.01
      Unpaired t-test.
      β-Tocopherol, mg0.370.140.350.120.45
      Unpaired t-test.
      γ-Tocopherol, mg12.74.712.04.50.54
      Unpaired t-test.
      δ-Tocopherol, mg3.21.63.01.10.49
      Unpaired t-test.
      a Unpaired t-test.
      b Chi-square test.
      The unadjusted odds ratios for low BMI and low body fat percentage per 100 μg/day increase in cryptoxanthin intake (95% confidence intervals) were 1.21 (1.01–1.48) and 1.33 (1.11–1.63), respectively (Table 5, Model 1). After adjustment for age and menopausal status, higher intake of cryptoxanthin was still significantly associated with both low BMI (1.24, 1.03–1.55) and low body fat percentage (1.37, 1.14–1.71) (Table 5, Model 2). Further, after adjustment for age, menopausal status, working, exercise, and smoking, the association of higher cryptoxanthin intake with both low BMI (1.22, 1.01–1.52) and low body fat percentage (1.36, 1.13–1.70) persisted (Table 5, Model 3).
      Table 5Multivariate analyses: the association between daily intake of cryptoxanthin and low BMI and body fat percentage.
      Low BMIModel 1
      Unadjusted OR.
      Model 2
      Multivariate logistic regression model, adjusting for age and menopausal status.
      Model 3
      Multivariate logistic regression model, adjusting for age, menopausal status, working, regularly exercising, and smoking.
      OR (95% CI)P valueOR (95% CI)P valueOR (95% CI)P value
      Crypto-xanthin
      Per 100μg/day increase of cryptoxanthin intake.
      1.21 (1.01–1.48)0.0381.24 (1.03–1.55)0.0221.22 (1.01–1.52)0.038
      Low body fat percentageModel 1
      Unadjusted OR.
      Model 2
      Multivariate logistic regression model, adjusting for age and menopausal status.
      Model 3
      Multivariate logistic regression model, adjusting for age, menopausal status, working, regularly exercising, and smoking.
      OR (95% CI)P valueOR (95% CI)P valueOR (95% CI)P value
      Crypto-xanthin
      Per 100μg/day increase of cryptoxanthin intake.
      1.33 (1.11–1.63)0.0011.37 (1.14–1.71)<0.0011.36 (1.13–1.70)0.001
      BMI, body mass index; OR, odds ratio; Cl, confidence interval.
      a Unadjusted OR.
      b Multivariate logistic regression model, adjusting for age and menopausal status.
      c Multivariate logistic regression model, adjusting for age, menopausal status, working, regularly exercising, and smoking.
      d Per 100 μg/day increase of cryptoxanthin intake.

      4. Discussion

      In this cross-sectional analysis of health parameters in 88 Japanese middle-aged women, high intake of cryptoxanthin was shown to be associated with low BMI and low body fat percentage levels.
      Carotenoids are a family of more than 600 plant pigments, and major dietary carotenoids include β-carotene, α-carotene, lycopene, lutein, and cryptoxanthin [
      • Krinsky N.I.
      • Johnson E.J.
      Carotenoid actions and their relation to health and disease.
      ]. They have been widely studied for their antioxidant capacity, and have been claimed to decrease the risk of various diseases, including certain cancers and eye diseases [
      • Krinsky N.I.
      • Johnson E.J.
      Carotenoid actions and their relation to health and disease.
      ,
      • Johnson E.J.
      The role of carotenoids in human health.
      ]. Cryptoxanthin is one of the major carotenoids found in tropical fruits [
      • Mangels A.R.
      • Holden J.M.
      • Beecher G.R.
      • Forman M.R.
      • Lanza E.
      Carotenoid content of fruits and vegetables: an evaluation of analytic data.
      ] such as papaya, orange, mango, and Satsuma mandarin, which is one of the most popular and highly consumed citrus fruits in Japan [
      • Takayanagi K.
      • Morimoto S.
      • Shirakura Y.
      • Mukai K.
      • Sugiyama T.
      • Tokuji Y.
      • Ohnishi M.
      Mechanism of visceral fat reduction in Tsumura Suzuki obese, diabetes (TSOD) mice orally administered β-cryptoxanthin from Satsuma mandarin oranges (Citrus unshiu Marc).
      ]. According to the food composition database in 2015 (Seventh Revised Edition) by the Ministry of Education, Culture, Sports, Science and Technology, the content in cryptoxanthin of Satsuma mandarin is 2000 μg/100 g, while papaya contains 820 μg/100 g, Valencia orange imported from the U.S.A. 130 μg/100 g, and mangoes 9 μg/100 g [
      Ministry of Education, Culture, Sports, Science and Technology, Standard Tables of Food Composition in Japan – 2015 – (Seventh Revised Edition).
      ]. Although cryptoxanthin is present in modest amounts in food sources, it is known as one of the most abundant carotenoids in serum, suggesting that cryptoxanthin is more bioavailable than other major carotenoid [
      • Zhu C.H.
      • Gertz E.R.
      • Cai Y.
      • Burri B.J.
      Consumption of canned citrus fruit meals increases human plasma β-cryptoxanthin concentration, whereas lycopene and β-carotene concentrations did not change in healthy adults.
      ]. Also, cryptoxanthin has been shown to suppress lipid peroxidation [
      • Stahl W.
      • Junghans A.
      • de Boer B.
      • Driomina E.S.
      • Briviba K.
      • Sies H.
      Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein.
      ] and free radical generation [
      • Murakami A.
      • Nakashima M.
      • Koshiba T.
      • Maoka T.
      • Nishino H.
      • Yano M.
      • Sumida T.
      • Kim O.K.
      • Koshimizu K.
      • Ohigashi H.
      Modifying effects of carotenoids on superoxide and nitric oxide generation from stimulated leukocytes.
      ], exhibiting antiatherogenic properties [
      • Matsumoto A.
      • Mizukami H.
      • Mizuno S.
      • Umegaki K.
      • Nishikawa J.
      • Shudo K.
      • Kagechika H.
      • Inoue M.
      Beta-cryptoxanthin, a novel natural RAR ligand, induces ATP-binding cassette transporters in macrophages.
      ].
      Previous studies have examined the association between certain carotenoids and body composition. One such study examined the serum concentration of five carotenoids including α-carotene, β-carotene, β-cryptoxanthin, zeaxanthin/lutein, lycopene in young adults aged 18–30 years and revealed that the serum concentrations of carotenoids except lycopene were inversely associated with the change in BMI [
      • Andersen L.F.
      • Jacobs D.R.
      • Gross M.D.
      • Schreiner P.J.
      • Dale Williams O.
      • Lee D.H.
      Longitudinal associations between body mass index and serum carotenoids: the CARDIA study.
      ]. Another study examined the association between serum concentrations of six carotenoids and metabolic syndrome in men and women aged 30–70 years who received health examinations [
      • Sugiura M.
      • Nakamura M.
      • Ogawa K.
      • Ikoma Y.
      • Matsumoto H.
      • Ando F.
      • Shimokata H.
      • Yano M.
      Associations of serum carotenoid concentrations with the metabolic syndrome: interaction with smoking.
      ]. The highest tertile of serum β-carotene overall, and of serum α-carotene and cryptoxanthin in current smokers, was shown to be related with a decreased odds ratio for metabolic syndrome. In animal experiments, a pair of studies using obese model mice revealed that oral administration of cryptoxanthin decreased body weight, abdominal adipose tissue weight, and serum lipid concentration [
      • Takayanagi K.
      • Morimoto S.
      • Shirakura Y.
      • Mukai K.
      • Sugiyama T.
      • Tokuji Y.
      • Ohnishi M.
      Mechanism of visceral fat reduction in Tsumura Suzuki obese, diabetes (TSOD) mice orally administered β-cryptoxanthin from Satsuma mandarin oranges (Citrus unshiu Marc).
      ,
      • Takayanagi K.
      Prevention of adiposity by the oral administration of β-cryptoxanthin.
      ]. The present study is the first to reveal a relationship between daily intake of cryptoxanthin and body composition in humans.
      Cryptoxanthin is a precursor of vitamin A (retinol) and thought to serve as a ligand for the retinoic acid receptor (RAR) [
      • Shirakura Y.
      • Takayanagi K.
      • Mukai K.
      • Tanabe H.
      • Inoue M.
      β-Cryptoxanthin suppresses the adipogenesis of 3T3-L1 cells via RAR activation.
      ]. RAR and retinoid X receptor (RXR) are the nuclear receptors that transduce retinoic acid signaling [
      • Matsumoto A.
      • Mizukami H.
      • Mizuno S.
      • Umegaki K.
      • Nishikawa J.
      • Shudo K.
      • Kagechika H.
      • Inoue M.
      Beta-cryptoxanthin, a novel natural RAR ligand, induces ATP-binding cassette transporters in macrophages.
      ] and promote its downstream target genes. Cryptoxanthin is suggested to downregulate the expression of peroxisome proliferator-activated receptor (PPAR)-γ through RAR activation, consequently preventing obesity [
      • Shirakura Y.
      • Takayanagi K.
      • Mukai K.
      • Tanabe H.
      • Inoue M.
      β-Cryptoxanthin suppresses the adipogenesis of 3T3-L1 cells via RAR activation.
      ]. Furthermore, cryptoxanthin was found to have antiatherogenic effects by inducing the expression of ATP-binding cassette transporter (ABC) A1 and G1 in macrophages [
      • Matsumoto A.
      • Mizukami H.
      • Mizuno S.
      • Umegaki K.
      • Nishikawa J.
      • Shudo K.
      • Kagechika H.
      • Inoue M.
      Beta-cryptoxanthin, a novel natural RAR ligand, induces ATP-binding cassette transporters in macrophages.
      ], which are responsible for cholesterol homeostasis facilitating the movement of sterols across lipid bilayers [
      • Yvan-Charvet L.
      • Wang N.
      • Tall A.R.
      Role of HDL ABCA1, and ABCG1 transporters in cholesterol efflux and immune responses.
      ]. High intake of cryptoxanthin could lead to low BMI and low body fat percentage levels through these mechanisms.
      Some studies reported that cryptoxanthin showed beneficial effects on the serum adipocytokine status [
      • Iwamoto M.
      • Imai K.
      • Ohta H.
      • Shirouchi B.
      • Sato M.
      Supplementation of highly concentrated β-cryptoxanthin in a satsuma mandarin beverage improves adipocytokine profiles in obese Japanese women.
      ] and insulin resistance and steatohepatitis [
      • Ni Y.
      • Nagashimada M.
      • Zhan L.
      • Nagata N.
      • Kobori M.
      • Sugiura M.
      • Ogawa K.
      • Kaneko S.
      • Ota T.
      Prevention and reversal of lipotoxicity-induced hepatic insulin resistance and steatohepatitis in mice by an antioxidant carotenoid, β-cryptoxanthin.
      ] without changing BMI or body weight. High intake of cryptoxanthin may not affect adiposity itself, but represent generally good consumption of fruits and vegetables, which leads to lower BMI.
      This study has several strengths and novel features. First, we assessed the consumption of 98 nutritional factors that are not limited to carotenoids. Although total energy intake [
      • Yoshita K.
      • Arai Y.
      • Nozue M.
      • Komatsu K.
      • Ohnishi H.
      • Saitoh S.
      • Miura K.
      • Group N.D.R.
      Total energy intake and intake of three major nutrients by body mass index in Japan: NIPPON DATA80 and NIPPON DATA90.
      ], fat intake [
      • Golay A.
      • Bobbioni E.
      The role of dietary fat in obesity.
      ], and sugar intake [
      • Trumbo P.R.
      • Rivers C.R.
      Systematic review of the evidence for an association between sugar-sweetened beverage consumption and risk of obesity.
      ] are considered to affect body mass and body fat, they were not significantly associated with body composition in our study, underscoring the relevance of cryptoxanthin intake. Next, as carotenoids are fat-soluble, the serum levels of these nutrients in obese women could be underestimated. Because we estimated the daily intake of nutritional factors from the BDHQ, this error was avoided. Finally, the target population of the current study, Japanese middle-aged women was ideal for examining the effect of cryptoxanthin due to their high consumption of Satsuma mandarins [
      • Takayanagi K.
      • Morimoto S.
      • Shirakura Y.
      • Mukai K.
      • Sugiyama T.
      • Tokuji Y.
      • Ohnishi M.
      Mechanism of visceral fat reduction in Tsumura Suzuki obese, diabetes (TSOD) mice orally administered β-cryptoxanthin from Satsuma mandarin oranges (Citrus unshiu Marc).
      ] as a source of the carotenoid.
      The present study also has some limitations. The number of participants was relatively small; the participants were healthy women, most of whom were not obese; the serum levels of the nutrients were not evaluated; and the causal relationship between body composition and cryptoxanthin remains unknown because this study was cross-sectional. In order to corroborate the observed association between body composition and cryptoxanthin consumption, prospective studies that enroll more obese women and evaluate both daily intake and serum levels of the nutrients are warranted.
      In conclusion, higher intake of cryptoxanthin was shown to be associated with low body mass and low body fat in Japanese middle-aged women, suggesting that consumption of Satsuma mandarin could help women to keep fit.

      Contributors

      AH participated in the project development, data collection, and data analysis.
      MT participated in the project development, data collection, and data analysis.
      MH participated in the data collection.
      MA participated in the data collection.
      YO participated in the data collection.
      KK participated in the data collection.
      TK participated in the project supervision.

      Conflicts of interest

      MT is in receipt of an unrestricted research grant from the Institute for Food and Health Service, Yazuya Co., Ltd.
      None of the other authors has a conflict of interest to declare.

      Funding

      MT received an unrestricted research grant from the Institute for Food and Health Service , Yazuya Co., Ltd.

      Ethical approval

      The study protocol was reviewed and approved by the Tokyo Medical and Dental University Review Board, and written informed consent was obtained from all participants. The study was conducted in accordance with the Declaration of Helsinki.

      Provenance and peer review

      This article has undergone peer review.

      References

        • Carr M.C.
        The emergence of the metabolic syndrome with menopause.
        J. Clin. Endocrinol. Metab. 2003; 88: 2404-2411
        • Rosano G.M.
        • Vitale C.
        • Tulli A.
        Managing cardiovascular risk in menopausal women.
        Climacteric. 2006; 9: 19-27
        • Lizcano F.
        • Guzmán G.
        Estrogen deficiency and the origin of obesity during menopause.
        BioMed Res. Int. 2014; 2014: 757461
        • Collins P.
        • Rosano G.
        • Casey C.
        • Daly C.
        • Gambacciani M.
        • Hadji P.
        • Kaaja R.
        • Mikkola T.
        • Palacios S.
        • Preston R.
        • Simon T.
        • Stevenson J.
        • Stramba-Badiale M.
        Management of cardiovascular risk in the peri-menopausal woman: a consensus statement of European cardiologists and gynaecologists.
        Eur. Heart J. 2007; 28: 2028-2040
        • Rosano G.M.
        • Vitale C.
        • Marazzi G.
        • Volterrani M.
        Menopause and cardiovascular disease: the evidence.
        Climacteric. 2007; 10: 19-24
        • Macdonald H.M.
        • New S.A.
        • Campbell M.K.
        • Reid D.M.
        Longitudinal changes in weight in perimenopausal and early postmenopausal women: effects of dietary energy intake, energy expenditure, dietary calcium intake and hormone replacement therapy.
        Int. J. Obes. Relat. Metab. Disord. 2003; 27: 669-676
        • Wing R.R.
        • Matthews K.A.
        • Kuller L.H.
        • Meilahn E.N.
        • Plantinga P.L.
        Weight gain at the time of menopause.
        Arch. Intern. Med. 1991; 151: 97-102
        • Golay A.
        • Bobbioni E.
        The role of dietary fat in obesity.
        Int. J. Obes. Relat. Metab. Disord. 1997; 21: S2-11
        • Kreider R.B.
        • Rasmussen C.
        • Kerksick C.M.
        • Wilborn C.
        • Taylor L.
        • Campbell B.
        • Magrans-Courtney T.
        • Fogt D.
        • Ferreira M.
        • Li R.
        • Galbreath M.
        • Iosia M.
        • Cooke M.
        • Serra M.
        • Gutierrez J.
        • Byrd M.
        • Kresta J.Y.
        • Simbo S.
        • Oliver J.
        • Greenwood M.
        A carbohydrate-restricted diet during resistance training promotes more favorable changes in body composition and markers of health in obese women with and without insulin resistance.
        Phys. Sportsmed. 2011; 39: 27-40
        • Trumbo P.R.
        • Rivers C.R.
        Systematic review of the evidence for an association between sugar-sweetened beverage consumption and risk of obesity.
        Nutr. Rev. 2014; 72: 566-574
        • Soares M.J.
        • Murhadi L.L.
        • Kurpad A.V.
        • Chan She Ping-Delfos W.L.
        • Piers L.S.
        Mechanistic roles for calcium and vitamin D in the regulation of body weight.
        Obes. Rev. 2012; 13: 592-605
        • Li Y.
        • Wang C.
        • Zhu K.
        • Feng R.N.
        • Sun C.H.
        Effects of multivitamin and mineral supplementation on adiposity, energy expenditure and lipid profiles in obese Chinese women.
        Int. J. Obes. (Lond.). 2010; 34: 1070-1077
        • Terauchi M.
        • Horiguchi N.
        • Kajiyama A.
        • Akiyoshi M.
        • Owa Y.
        • Kato K.
        • Kubota T.
        Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized double-blind, placebo-controlled pilot study.
        Menopause. 2014; 21: 990-996
        • Sasaki S.
        • Yanagibori R.
        • Amano K.
        Self-administered diet history questionnaire developed for health education: a relative validation of the test-version by comparison with 3-day diet record in women.
        J. Epidemiol. 1998; 8: 203-215
        • Okubo H.
        • Sasaki S.
        • Rafamantanantsoa H.H.
        • Ishikawa-Takata K.
        • Okazaki H.
        • Tabata I.
        Validation of self-reported energy intake by a self-administered diet history questionnaire using the doubly labeled water method in 140 Japanese adults.
        Eur. J. Clin. Nutr. 2008; 62: 1343-1350
        • Kobayashi S.
        • Honda S.
        • Murakami K.
        • Sasaki S.
        • Okubo H.
        • Hirota N.
        • Notsu A.
        • Fukui M.
        • Date C.
        Both comprehensive and brief self-administered diet history questionnaires satisfactorily rank nutrient intakes in Japanese adults.
        J. Epidemiol. 2012; 22: 151-159
        • Kobayashi S.
        • Murakami K.
        • Sasaki S.
        • Okubo H.
        • Hirota N.
        • Notsu A.
        • Fukui M.
        • Date C.
        Comparison of relative validity of food group intakes estimated by comprehensive and brief-type self-administered diet history questionnaires against 16 d dietary records in Japanese adults.
        Public Health Nutr. 2011; 14: 1200-1211
        • Krinsky N.I.
        • Johnson E.J.
        Carotenoid actions and their relation to health and disease.
        Mol. Aspects Med. 2005; 26: 459-516
        • Johnson E.J.
        The role of carotenoids in human health.
        Nutr. Clin. Care. 2002; 5: 56-65
        • Mangels A.R.
        • Holden J.M.
        • Beecher G.R.
        • Forman M.R.
        • Lanza E.
        Carotenoid content of fruits and vegetables: an evaluation of analytic data.
        J. Am. Diet. Assoc. 1993; 93: 284-296
        • Takayanagi K.
        • Morimoto S.
        • Shirakura Y.
        • Mukai K.
        • Sugiyama T.
        • Tokuji Y.
        • Ohnishi M.
        Mechanism of visceral fat reduction in Tsumura Suzuki obese, diabetes (TSOD) mice orally administered β-cryptoxanthin from Satsuma mandarin oranges (Citrus unshiu Marc).
        J. Agric. Food Chem. 2011; 59: 12342-12351
      1. Ministry of Education, Culture, Sports, Science and Technology, Standard Tables of Food Composition in Japan – 2015 – (Seventh Revised Edition).
        2016 (http://www.mext.go.jp/a_menu/syokuhinseibun/1365297.htm (accessed 5/10/16))
        • Zhu C.H.
        • Gertz E.R.
        • Cai Y.
        • Burri B.J.
        Consumption of canned citrus fruit meals increases human plasma β-cryptoxanthin concentration, whereas lycopene and β-carotene concentrations did not change in healthy adults.
        Nutr. Res. 2016; 36: 679-688
        • Stahl W.
        • Junghans A.
        • de Boer B.
        • Driomina E.S.
        • Briviba K.
        • Sies H.
        Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein.
        FEBS Lett. 1998; 427: 305-308
        • Murakami A.
        • Nakashima M.
        • Koshiba T.
        • Maoka T.
        • Nishino H.
        • Yano M.
        • Sumida T.
        • Kim O.K.
        • Koshimizu K.
        • Ohigashi H.
        Modifying effects of carotenoids on superoxide and nitric oxide generation from stimulated leukocytes.
        Cancer Lett. 2000; 149: 115-123
        • Matsumoto A.
        • Mizukami H.
        • Mizuno S.
        • Umegaki K.
        • Nishikawa J.
        • Shudo K.
        • Kagechika H.
        • Inoue M.
        Beta-cryptoxanthin, a novel natural RAR ligand, induces ATP-binding cassette transporters in macrophages.
        Biochem. Pharmacol. 2007; 74: 256-264
        • Andersen L.F.
        • Jacobs D.R.
        • Gross M.D.
        • Schreiner P.J.
        • Dale Williams O.
        • Lee D.H.
        Longitudinal associations between body mass index and serum carotenoids: the CARDIA study.
        Br. J. Nutr. 2006; 95: 358-365
        • Sugiura M.
        • Nakamura M.
        • Ogawa K.
        • Ikoma Y.
        • Matsumoto H.
        • Ando F.
        • Shimokata H.
        • Yano M.
        Associations of serum carotenoid concentrations with the metabolic syndrome: interaction with smoking.
        Br. J. Nutr. 2008; 100: 1297-1306
        • Takayanagi K.
        Prevention of adiposity by the oral administration of β-cryptoxanthin.
        Front. Neurol. 2011; 2: 67
        • Shirakura Y.
        • Takayanagi K.
        • Mukai K.
        • Tanabe H.
        • Inoue M.
        β-Cryptoxanthin suppresses the adipogenesis of 3T3-L1 cells via RAR activation.
        J. Nutr. Sci. Vitaminol. (Tokyo). 2011; 57: 426-431
        • Yvan-Charvet L.
        • Wang N.
        • Tall A.R.
        Role of HDL ABCA1, and ABCG1 transporters in cholesterol efflux and immune responses.
        Arterioscler. Thromb. Vasc. Biol. 2010; 30: 139-143
        • Iwamoto M.
        • Imai K.
        • Ohta H.
        • Shirouchi B.
        • Sato M.
        Supplementation of highly concentrated β-cryptoxanthin in a satsuma mandarin beverage improves adipocytokine profiles in obese Japanese women.
        Lipids Health Dis. 2012; 11: 52
        • Ni Y.
        • Nagashimada M.
        • Zhan L.
        • Nagata N.
        • Kobori M.
        • Sugiura M.
        • Ogawa K.
        • Kaneko S.
        • Ota T.
        Prevention and reversal of lipotoxicity-induced hepatic insulin resistance and steatohepatitis in mice by an antioxidant carotenoid, β-cryptoxanthin.
        Endocrinology. 2015; 156: 987-999
        • Yoshita K.
        • Arai Y.
        • Nozue M.
        • Komatsu K.
        • Ohnishi H.
        • Saitoh S.
        • Miura K.
        • Group N.D.R.
        Total energy intake and intake of three major nutrients by body mass index in Japan: NIPPON DATA80 and NIPPON DATA90.
        J. Epidemiol. 2010; 20: S515-23