Clinical Nutrition xxx (2015) 1e8

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Review

Dietary intake and nutritional status of micronutrients in adults with cystic fibrosis in relation to current recommendations Li Li a, Shawn Somerset a, b, * a b

School of Medicine, Griffith Health Institute, Griffith University, Brisbane, Queensland, Australia School of Allied Health, Faculty of Health Sciences, Australian Catholic University, Brisbane, Queensland, Australia

a r t i c l e i n f o

s u m m a r y

Article history: Received 21 August 2014 Accepted 12 June 2015

An increased prevalence of cystic fibrosis (CF) related complications such as impaired bone health and diabetes has accompanied increased survival of patients with CF. This review was conducted to determine the extent to which adults with CF are meeting current nutrition recommendations for micronutrients in association with CF-related complications management. Although dietary intake and nutritional status in CF has improved significantly in recent decades, micronutrient status seems to have diverged. While vitamin A and E intakes appear adequate, frequent vitamin D and K deficiency/insufficiency and compromised bone health in CF, occurs despite supplementation. Although deficiency of water-soluble vitamins and minerals is uncommon, ongoing surveillance will enhance overall health outcomes, particularly in cases of CF-related liver disease and deteriorated lung function and bone health. Salt and fluid status in CF may also need attention due to diminished thirst sensation and voluntary rehydration. Further investigation in micronutrient status optimisation in CF will inform the development of more effective and targeted nutrition therapies to enable integration of more refined recommendations for micronutrient intakes in CF based on individual needs and disease progression. © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Keywords: Nutritional status Nutrient status Dietary intake Cystic fibrosis Micronutrients

1. Introduction It is now common for individuals with CF to survive well into adulthood thanks to improved diagnosis and treatment, including nutritional management [1]. Despite overall improved nutritional status, dietary intake and status of several micronutrients seem to be associated with CF related chronic conditions such as impaired bone health and CF related diabetes (CFRD), the prevalence of which has increased with the improved survival in CF [1,2]. This change of epidemiology has been accompanied by regular

Abbreviations: CF, cystic fibrosis; CFRD, cystic fibrosis-related diabetes; CFRLD, cystic fibrosis-related liver disease; PI, exocrine pancreatic insufficiency; EAR, estimated average requirement; NNR, Nordic Nutrition Recommendations; PS, pancreatic sufficiency; RNI, Reference Nutrient Intake; PERT, pancreatic enzyme replacement therapy; CRP, C-reactive protein; BMD, bone mineral density; 25(OH) D, 25-hydroxyvitamin D; 1,25(OH)2D, 1,25-dihydroxyvitamin D; UV, ultraviolet; PTH, parathyroid hormone; DBP, vitamin D binding protein; PIVKA-II, proteins induced by vitamin K absence-II; %ucOC, undercarboxylated osteocalcin; ENaC, epithelium Naþ channel. * Corresponding author. School of Allied Health, Faculty of Health Sciences, Australian Catholic University, Brisbane, Queensland, PO Box 456, Virginia 4014, Australia. Tel.: þ61 7 3623 7183. E-mail address: [email protected] (S. Somerset).

monitoring of dietary intakes and nutritional status, and frequent updating of specific outdated dietary recommendations in CF. From this perspective, the aim of this review was to compare recent reports of actual dietary intake and nutritional status of micronutrients, with relevant dietary recommendations for CF to inform further refinement of dietary micronutrient recommendations for CF, in view of increased prevalence of CF related comorbidities in this population as life expectancy increases.

2. CF specific recommendations Dietary micronutrient recommendations for CF in various countries [4e13] summarised in Tables 1 and 2 were developed based on best available evidence and expert consensus at the time. Given the substantial changes in CF treatment and consequent improvements in life expectancy, many of these may be outdated for current practice. These recommendations address challenges of micronutrient intake, particularly of fat-soluble vitamins, mainly due to dysfunctions of the digestive system including exocrine pancreatic insufficiency (PI) [14]. The recommendations for fatsoluble vitamins for different age groups are more variable between countries, and have been complicated by the various age

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Please cite this article in press as: Li L, Somerset S, Dietary intake and nutritional status of micronutrients in adults with cystic fibrosis in relation to current recommendations, Clinical Nutrition (2015), http://dx.doi.org/10.1016/j.clnu.2015.06.004

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L. Li, S. Somerset / Clinical Nutrition xxx (2015) 1e8

Table 1 International nutrition recommendations for adults with CF e vitamins (Refs. [4e13]). Scope

Vitamin A (IU) (1 IU ¼ 0.33 mg)

US CFF 1992 [4]

All ages

e 1e2 standard adult e 200e400/day vitamin/day

European CFS 2002 [5]

All ages

e 400/day

UK CFT 2002 [6]

All ages

e 4000e10,000 fat-soluble preparation/day for PI; e Always 20,000 e 0.5e1 mg/kg b-carotene for PI and very low plasma and lipoprotein levels e 4000e10,000/day

UK CFT 2004 [7]

CFRD at all ages

US CFF 2004 [8]

US CFF 2005 [9] Australasian Guidelines 2006 [10]

Vitamin E (IU) (1 IU ¼ 0.67 mg)

Vitamin D (IU) (1 IU ¼ 0.025 mg)

Vitamin K (mg)

e 5000  2 weekly if on antibiotics or with cholestatic liver disease e 1000/daye10,000/week e 400e2000/day for PI, for PI and cholestasis; esp. northern countries; e 10,000/day for e 25(OH)D preferred demonstrated or suspected deficiency

NIa

e 150e300/day

e 800e2000/day

e 10,000/day; e Suggestion not recommendation

e 4000e10,000/day

e 150e300/day

e 800e2000/day

e 10,000/day; e Suggestion not recommendation

Adults

e 10,000/day

e 200e400/day

e 400e800/day

e Supplement if documented poor dietary intake; e Parenteral vitamin B12 possible for extensive surgery for MIc e Supplement if documented poor dietary intake; e Parenteral vitamin B12 possible for extensive surgery for MIc NIa

All ages All ages

NIa e 2500e5000/day

NIa e 150e500/day

e 50,000e2  50,000/wk e 400e1000/day

US CFF 2010 [11] CFRD at all ages

e CF specific multivitamins

European CFS 2011 [12]

NIa

e CF specific e CF specific multivitamins; multivitamins; e Or a multivitamin e Or a multivitamin and additional vitamin D and additional vitamin E a NI e 1000e5000/day; e Adjusted based on 25(OH)D > 20 ng/mL (50 nM); e Preferably D3 NIa e 800e2000 D3/dayb

e 2500e5000/week; e Additional 2500e5000/wk if frequent antibiotic courses or haemoptysis history e 300e500/day NIa e 300e500/day e Supplement if inadequate dietary intake and/or evidence of deficiency; e Parenteral vitamin B12 if terminal ileum resected e CF specific multivitamins; e CF specific multivitamins e Or a multivitamin and additional vitamin K

All ages

US CFF 2012 [13] Vitamin D NIa for all ages a b c

NIa

Water-soluble vitamins

e Parenteral 100 mg vitamin B12/month for extensive terminal ileum resection; e 100 mg vitamin C/day for deficiency

e 1000e10,000/day

NIa

NIa

NIa

NI ¼ no information. 1600e6000 D3/day if 25(OH)D within 20e30 ng/ml (50e75 nM); 10,000 D3/day if 25(OH)D persists within 20e30 ng/ml (50e75 nM) or 35% EIa NNRm 2004

Water-soluble vitamins

PI median supplementation dosage: 3000 mg Vit A, 20 mg Vit D, 200 mg vit E PI: vit K supplemented only if uncontrolled PI or on long course antibiotics PS participants: 200 mg vit E supplement Vit D: 23.2 ± 12.6 mg/day, 81% participants > AI,i 5% > ULj Vit Ac: 3706 ± 2108 mg, mean > ULj

RE (mg): 1307 ± 732, mean > NNR (females: 700 mg/day, males 900 mg/day) Vit D3 (mg): 5.8 ± 4.3, NNRm (females 8 mg/day, males 10 mg/day) l

EI ¼ energy intake. EAR ¼ estimated average requirement. EER ¼ estimated energy requirement. NI ¼ no information. EER-CFF ¼ estimated energy requirement derived from US CFF 1992 (Ramsey et al. [4]). DRI ¼ dietary reference intake. AI ¼ average intake. UL ¼ upper limit. RDA ¼ recommended daily allowance. Retinol equivalents (RE), 1 RE ¼ 1 mg retinol. NNR ¼ Nordic Nutrition Recommendations.

m

NI

f

Minerals NI

Biochemical results

f

CF: 10.8% low serum vit D CF: 2.7% low serum vit A

i

Folate: 30% participants > ULj Vit B6: 1% participants > ULj

Calcium: 89% Participants > AI, 31% > ULj Magnesium: 91% participants > RDA,k mean > ULj

Niacin: mean > ULj

Phosphorus: 100% participants > RDA,k 8% > ULj Calcium (mg): 1481 ± 627, mean > NNRm

Thiamin (mg): 1.8 ± 0.6, mean > NNRm Riboflavin (mg): 2.3 ± 0.9, mean > NNRm Vitamin C (mg): 121 ± 67, mean > NNRm

Iron (mg): 13.4 ± 5.1, NNRm for male Magnesium (mg): 402 þ 130 > NNRm

CF: none with low serum vit E Serum 25(OH)D: 19.4 ± 13.1 ng/mL, 39% < 37.5 mmol/L (15 ng/mL), significant correlation with generalised and bone pain

NIf

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Please cite this article in press as: Li L, Somerset S, Dietary intake and nutritional status of micronutrients in adults with cystic fibrosis in relation to current recommendations, Clinical Nutrition (2015), http://dx.doi.org/10.1016/j.clnu.2015.06.004

Table 3 Cross-sectional dietary surveys published since 2000 e micronutrients.

L. Li, S. Somerset / Clinical Nutrition xxx (2015) 1e8

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Table 4 Longitudinal dietary survey published since 2000 e micronutrients. Study

CF group

Reference/control

Fat soluble vitamins

Walkowiak and Przyslawski, n ¼ 38 in 1994e1998 Polish RDAa (version unspecified) 2003 [16] Prospective Age 11 ± 1.1 years, range CFF consensus 1992 (EIb > 120% 2e18 years RDA,a fat 40% EI,b protein 15% EIb 7-day weighted food record a b c

Water soluble Minerals Biochemical results vitamins

1994: Vit A 182 ± 6% RDAa; NIc Vit E 862 ± 57% RDAa 1998: Vit A 259 ± 10% RDA,a Vit E 2057 ± 55% RDAa >1994 (P < 0.05)

NIc

Increased blood vit A and E (P < 0.05) Vit E deficiency common

RDA ¼ recommended daily allowance. EI ¼ energy intake. NI ¼ no information.

status, despite routine vitamin D supplementation according to the relevant CF guidelines [32,34,37,43,47,48]. Prevalence of deficiency varies between studies and countries, depending on different cut-off points set at the time. Consequently, conflicting observations have been reported, although the mean 25(OH)D levels were usually on the lower end of the normal ranges of the general population [32,34,37,49,50]. The recently updated vitamin D guidelines for CF [13] may consolidate the cut-off points for vitamin D deficiency diagnosis and supplementation regimens for further studies. In any case, adherence to PERT seems unlikely to be the major contributor of vitamin D deficiency, because deficiency has occurred even in pancreatic sufficient patients and no association between serum 25(OH)D level and pancreatic status could be established [50]. Proposed causes of suboptimal vitamin D status in CF include diminished photosynthesis, intestinal absorption, storage, and metabolism, and increased urinary excretion [37,46]. Photosynthesis of vitamin D could theoretically compensate for inadequacy, particularly in those with frequent exposure to sunlight. Evidence for this has been demonstrated in a recent longitudinal study [51]. Serum concentrations of 25(OH)D in CF were found to be closely associated with environmental ultraviolet (UV) B intensity in previous months, and concentrations were similar to those in healthy controls. However, the exact amount of UV exposure of the participants was not reported and may have confounded the findings. Impaired photosynthesis in CF can be related to decreased exposure to UVB radiation potentially secondary to the photosensitivity induced by certain antibiotics, although data on outdoor activity levels in CF is absent [37,46]. Adherence to UVB therapy using UV lamps seems to be poor and evidence for its efficacy limited [13]. It is possible that membrane phospholipid anomalies can influence the conversion of previtamin D3 to D3. [37,46] Defective or absent CFTR channels in the epidermis may also play a role [46]. Decreased intestinal absorption is not only caused by PI (which can be at least partially compensated by PERT), but potentially also decreased bile acid availability [46]. Furthermore, the intestinal carrier for vitamin D3 may be down-regulated in the absence of CFTR channels [37,46]. It has been proposed that reduced vitamin D stores in CF may relate to decreased fat mass [37,46]. Supressed hepatic and renal hydroxylation to activate vitamin D to 1,25(OH)2D may also occur, possibly due to hepatocyte damage secondary to CFTR dysfunction in ductal cells and altered interaction between aberrant CFTR and the upstream signalling pathway for parathyroid hormone (PTH) activation, respectively [46]. PTH, concurrent with serum calcium, phosphorus and 1,25(OH)2D itself, tightly regulates serum 1,25(OH)2D levels. Absorption and metabolism of vitamin D seem to vary according to supplement formulation as well [44,46,48,52,53]. Animal-derived cholecalciferol (vitamin D3) [53] appears to outperform plant-derived ergocalciferol (vitamin D2) [48,52,54] at much lower dosages in normalising serum 25(OH)D levels in adults with CF. This efficiency is reflected in the updated CFF recommendations for vitamin D supplementation

[13] (Table 1), where cholecalciferol has replaced ergocalciferol in previous recommendations [9] as the preferred choice for CF. Another potential contributor to vitamin D deficiency in CF is augmented urinary excretion of 25(OH)D due to increased urinary loss of vitamin D binding protein (DBP) [46]. Increased loss of DBP-25(OH)D complex is associated with suppressed expression of relevant receptors in the proximal tubule [55]. For the mechanisms elaborated above, vitamin D status is commonly compromised in CF. Despite some controversial evidence [34,49,50,56], this compromised status has generally been accepted as one of the main contributors to low BMD in CF [57,37]. Although this review focuses on adults with CF, attention should also be given to the role of vitamin D status in bone mass acquisition in the younger CF population due to early incidence of impaired bone health in childhood [12,56]. Evidence for extra-skeletal functions of vitamin D in CF is accumulating. For example, vitamin D is likely to improve respiratory function through its role in antimicrobial peptide and cytokine production and its association with muscle strength [40,41,43,44]. It is also associated with CFRD through potential involvement in islet function regulation, insulin production and secretion, and insulin sensitivity [42,46]. Its role in bone health and immune response has also implied an importance in pain management in CF [45]. Despite such importance of vitamin D in CF, a recent Cochrane review was unable to make definitive conclusions about the efficacy of vitamin D supplements due to the limited number of RCTs and small sample sizes involved [57]. Therefore, further surveillance of vitamin D status and supplementation in CF suggested by the new CFF recommendations [13] is worthwhile. Additionally, the exact impact of vitamin D status on bone mineralisation, skeletal health and extra-skeletal health in CF and the relevant physiology requires further exploration. Although not reflected in the nutrient status studies reviewed here, the high risk of low BMD and osteoporosis in CF and the association between vitamin K insufficiency and decreased BMD and abnormal bone turnover biomarkers [58,59] has drawn attention to vitamin K insufficiency in CF. In general, clinical deficiency has been uncommon over at least the past two decades [60e62]. However, suboptimal vitamin K status in CF has been a common concern [60e62], not least because of disruptions of gut function and consequent dysbiosis in the CF colon, thus compromising endogenous vitamin K production [63]. Suboptimal status has been indicated by elevated plasma proteins induced by vitamin K absence-II (PIVKA-II) levels and serum undercarboxylated osteocalcin (% ucOC), two sensitive clinical markers for early vitamin K deficiency [60e62,64]. This biochemical insufficiency occurs despite supplementation at high doses or adherence to the CF dietary recommendations at the time [62,64,65]. One recent study demonstrated subclinical deficiencies in the majority of participants with CF, despite a significant decrease in overall %ucOC and increase in serum vitamin K levels following 1 mg/day and 5 mg/day vitamin K1 supplementation for one month to correct deficiency [66].

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However, the small sample size was insufficient to distinguish between the efficacy of 1 mg/day and 5 mg/day regimens and controls were absent. Thus, the recent Cochrane review found only weak evidence for routine vitamin K supplementation for CF, since only two trials met the Cochrane selection criteria [67]. Similar to other fat-soluble vitamins, the underlying mechanism for vitamin K deficiency and insufficiency are most likely multifactorial, including impaired pancreatic and hepatic function, pulmonary infections requiring frequent antibiotic treatment, major small intestinal resection and insufficient supplementation [60e62,68]. Given its role in posttranslational carboxylation of osteocalcin and other bone mineralisation proteins [59,67,69], vitamin K has received more attention in recent CF recommendations (Table 1). Indeed, a dose > 1 mg/day can normalise PIVKA-II and %ucOC values [62]. In summary, despite routine supplementation according to current CF recommendations, vitamin D and K status are often suboptimal in CF. The prevalence of vitamin E deficiency is still debated and long term safety of current supplementation regimens of vitamin A needs further evaluation. Investigating the optimal dose of these vitamins in CF in relation to pulmonary function and complications such as CFRD and skeletal health requires further long term and longitudinal intervention studies. 3.2. Water-soluble vitamins and minerals In contrast to fat-soluble vitamins, the status of mineral and water-soluble vitamins in CF has received less attention (Tables 3 and 4), probably due to low prevalence of reported deficiency. The two studies that surveyed water-soluble vitamin intake reported adequacy of intake in the specific population studied [18,19]. Indeed, thiamin and riboflavin intakes in participants with CF and PI averaged higher than the country-specific recommendations for the general population, and these values did not include the possible contribution of water-soluble vitamin supplementation [19]. Nevertheless, isolated cases of severe or even persistent riboflavin deficiency, accompanied by deficiencies of thiamin, pyridoxine and iron, have been reported in children with CF [70]. This may be related to a decreased bile pool as liver abnormalities occurred in two of the three cases. Suppressed riboflavin absorption can occur in cases of bile salts deficiency in hepatitis, cirrhosis and biliary obstruction, despite unknown mechanisms [71]. Dietary intakes of certain minerals have also been reported in CF. One study found lower mean iron intake in females with CF and PI than the recommendation for healthy females [19]. This may be of concern, since functional iron deficiency and anaemia have been observed in over half of adult CF patients and have been consistently related to declined lung function and chronic inflammation, with the possible contribution of ageing and poor nutritional status or vitamin deficiency [72e74]. However, iron supplementation is cautioned, since iron overload may exacerbate the oxidative stress from chronic inflammation in CF [75]. Suppressed plasma zinc levels during pulmonary exacerbation have also been observed [75], although this suppression may not represent the overall zinc status in CF. Plasma zinc is classically thought to account for less than 1% of the total body pool [76]. A small caseecontrol study identified altered copper distribution in CF plasma and cells [77]. Potential mechanisms such as abnormal copper homoeostasis and inflammatory response in CF need further investigation [77]. Calcium intake in CF seems generally sufficient (Table 3) [18,19]. Considering its importance in bone mineralisation and the paucity of data on optimal intake for bone health in CF, calcium status in CF should probably be assessed regularly and studies on the optimal supplementation dosage are warranted [9]. Magnesium intake also appears sufficient when

compared with the country-specific population recommendations (Table 3) [18,19]. However, whether such apparent sufficiency is adequate for those with CF is debatable and magnesium seems to have multiple roles such as assisting airway mucus clearance, maintaining immune function and reducing oxidative stress through the action of glutathione reductase [78]. In particular, common CF medications such as aminoglycoside antibiotics and calcineurin inhibitors for post-transplantation patients can increase renal wasting of magnesium, and proton-pump inhibitors may increase gastrointestinal loss and/or impair absorption [79]. Despite the paucity of published data on dietary intake of selenium, its serum levels, which are crucial for glutathione peroxidase to protect from oxidative stress, have also been reported to be lower in CF than in healthy controls [80,81]. Therefore, monitoring the intakes and nutritional status of magnesium and selenium and evaluating their therapeutic value in CF treatment may be useful for future studies. Notwithstanding the lack of water-soluble vitamin and mineral deficiencies reported, routine surveillance of suboptimal status of these nutrients will contribute to overall health outcomes in CF, particularly in cases of CFLRD and compromised lung function and bone health. Although absent from dietary surveys and rare in CF recommendations (Table 2), salt and fluid status in CF, particularly in hot climates and after exercise, may be of concern. Excessive sweat loss of Naþ and Cl in CF has been well documented [82e84]. The impact of CF on sweat secretion occurs in the duct of sweat gland. Normally, Cl and Naþ are reabsorbed, resulting in a final sweat secretion that is hypotonic in healthy people [85]. In CF, absence/decrease of functional CFTR in the sweat glands leads to impeded reabsorption of Cl. This is accompanied by suppressed Naþ reabsorption, as CFTR Cl conductance is essential for Naþ reabsorption via the epithelium Naþ channel (ENaC) [86]. Consequently, Naþ concentration in CF sweat is typically 3e5 times higher than healthy controls [85,87]. The Cl-concentration increases similarly, but Kþ concentration is less affected. However, the exact amount of loss varies according to sweating rate, extent of dehydration and possibly the influence of hormones that regulate salt and water retention [84,85,87]. Interestingly, individuals with CF seem to drink significantly less water than healthy controls with the same dehydration level, even in the case of similar perceived thirst [82,84]. This adaptation seems to help restore the plasma concentration of these electrolytes, which are tightly regulated in humans, but fails to restore plasma volume. Since only hypotonic fluids were provided in these studies, it will be interesting to compare the drinking pattern of CF and healthy controls when isotonic and hypertonic fluids are provided. In fact, one earlier study provided beverages for rehydration to induce higher fluid intake after dehydration in CF children, including two hypertonic fluids with 30 mmol/L and 50 mmol/L of NaCl [88]. Neither of these beverages induced higher voluntary drinking in the CF group, although the increase in intake of the 50 mmol/L NaCl beverage approached significance. These results indicate that salt and perhaps electrolyte replacement after dehydration in CF is both critical and challenging, particularly in hot weather and/or with prolonged exercise. This is reflected in those whose plasma Naþ was found to be low despite meeting recommended Naþ intake [83,89]. However, a cautionary approach to electrolyte replacement is required in CF with liver cirrhosis and portal hypertension to prevent further development of ascites [90]. 4. Conclusion In a context of increased CF-related complications with improved life expectancy in people with CF, major studies

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published on dietary intake and micronutrient status in CF recently have demonstrated an overall improved but diverged dietary intake and biochemical status of micronutrients. There has been concern about excessive vitamin A and E intakes, particularly with watersoluble formulations, whereas suboptimal vitamin D and K status have been frequently encountered despite supplementation regimes equivalent to or higher than current recommendations. Vitamin D and K status are of particular concern because of their role in bone health, which is often impaired in CF. Water-soluble vitamins and minerals such as iron, zinc, calcium, magnesium and selenium seem to be less problematic when compared with population recommendations, although their role in CF is not as well understood as fat-soluble vitamins. The extent to which nutritional supplementation has alleviated micronutrient deficiency and contributed to potential overdose has not been quantified, rendering accurate assessment of and hence refined recommendation for such supplementation difficult. The optimal dosages of such long-term micronutrient supplementation require further investigation, so that safety and effect on reducing lung disease severity and CF related complications are balanced. The loss of fluid and electrolytes in sweat may not be as easily replenished as in the general population due to diminished sensation of thirst induced by excessive Naþ loss via sweat. The necessity to recommend voluntary rehydration with appropriate electrolyte levels irrespective of signs and symptoms of thirst and salt loss in hot climate and/or prolonged exercise warrants further evaluation. Such varied nutritional profiles and requirements of micronutrients in CF have arisen with the increased prevalence of CFrelated chronic complications as the life expectancy rises [1]. To integrate these requirements into nutritional therapies that meet their unique nutritional needs, research to determine optimal biochemical status and intakes of micronutrients according to disease progression and healthy ageing and continued regular surveillance of the safety and adequacy of individual nutrients on both the population and individual level are called for to develop more refined micronutrient recommendations for CF. Statement of authorship LL helped conceive of the study and drafted the manuscript; SS conceived of the study and edited the manuscript. Both authors read and approved the final manuscript. Sources of funding LL received the Australian Postgraduate Award from Griffith University, PhD Researcher Grant Scheme from Population and Social Health Research Program, Griffith Health Institute, Griffith University, and PhD Student Fellowship from The Australian Cystic Fibrosis Research Trust (ACFRT). None of the funding sources were involved in the conception of the study or the preparation of the manuscript. Conflict of interest None declared. References [1] Parkins MD, Parkins VM, Rendall JC, Elborn S. Changing epidemiology and clinical issues arising in an ageing cystic fibrosis population. Ther Adv Respir Dis 2011;5:105e19. [2] Matel JL. Nutritional management of cystic fibrosis. J Parenter Enteral Nutr 2012;36:60Se7S. [4] Ramsey B, Farrell P, Pencharz P. Nutritional assessment and management in cystic fibrosis: a consensus report. Am J Clin Nutr 1992;55:108e16.

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Please cite this article in press as: Li L, Somerset S, Dietary intake and nutritional status of micronutrients in adults with cystic fibrosis in relation to current recommendations, Clinical Nutrition (2015), http://dx.doi.org/10.1016/j.clnu.2015.06.004

Dietary intake and nutritional status of micronutrients in adults with cystic fibrosis in relation to current recommendations.

An increased prevalence of cystic fibrosis (CF) related complications such as impaired bone health and diabetes has accompanied increased survival of ...
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