The effect of omega-3 polyunsaturated fatty acid intake on blood levels of omega-3s in people with chronic atherosclerotic disease: a systematic review.

CONTEXT: Atherosclerosis is a systemic pro-inflammatory and pro-oxidative disease, accounting for approximately a third of deaths globally. It has been proposed that omega-3s, through their antioxidant and anti-inflammatory properties, mitigate atherosclerotic disease progression. However, due to the systemic pro-inflammatory and pro-oxidative state of atherosclerosis, it is proposed that patients with atherosclerotic disease may have higher omega-3 requirements than the average requirement, due to increased nutrient utilization in anti-inflammatory and anti-oxidant processes. OBJECTIVE: The aim of this review was to determine what dose and duration of omega-3 supplementation is required to reach a therapeutic blood level of omega-3s (eicosapentaenoic acid ≥150 µg/mL or omega-3 index ≥8%) in people with chronic atherosclerotic disease. DATA SOURCES: This systematic review comprehensively searched MEDLINE, Emcare, Scopus, and CINAHL using key search terms for atherosclerotic disease, omega-3, supplementation, and blood levels of omega-3s. DATA EXTRACTION: Two reviewers independently screened 529 randomized controlled trials (RCTs) supplementing omega-3s in patients with chronic atherosclerotic disease. DATA ANALYSIS: In total, 25 journal articles from 17 original RCTs were included and assessed quantitatively. Supplementation at 1.8 g to 3.4 g per day for a 3-month-6-month duration, and at 4.4 g and above for as little as 1 month-6 months were identified as the most effective dosage ranges for increasing blood levels of omega-3s to therapeutic levels in people with atherosclerotic disease. CONCLUSIONS: Consideration should be given to routine omega-3 supplementation and to increasing the omega-3 dietary recommendations and upper limits of daily intake to improve clinical outcomes and reduce the risk of cardiac mortality in this population.

Validation of a Short Food Frequency Questionnaire to Measure Dietary Intake of a Selection of Micronutrients in Oncology Patients Undergoing Systemic Therapy.

Dietary intake, specifically consumption of anti-inflammatory micronutrients, can play a role in both cancer initiation as well as the treatment-related outcomes experienced by patients receiving systemic cancer therapy. Increasing research is being conducted to determine whether micronutrient supplementation can aid in altering the tumor microenvironment (TME), reducing inflammatory side effects and immune-related adverse events (irAEs). However, further research pertaining to the adequacy of dietary micronutrient intake is indicated in the oncology cohort. Currently, no tool measuring dietary intakes of various micronutrients exists in the oncology population. In this study, a 21-item food frequency questionnaire (FFQ) measuring intakes of 14 different micronutrients was validated using diet history as the reference method in 112 oncology patients. Bland Altman plot and Passing Bablok regression analysis were conducted to determine agreement between the two methods. The results showed adequate agreement between FFQ and diet history for 12 nutrients including copper, iron, vitamins A, E, and D, alpha linolenic acid (ALA), long-chain omega 3 fatty acids (LC n3-FA), arginine, glutamic acid, isoleucine, leucine, and valine. This 21-item FFQ, which takes an average of 10 min to complete, can be utilized as a quick screening tool to determine adequacy for 12 different micronutrients in place of a diet history.

Development and Validation of a Short Food Frequency Questionnaire to Measure Dietary Intake of a Selection of Immune-Modulating Nutrients in Patients with Established Peripheral Arterial Disease.

Nutrients with the ability to modulate the immune system (immune-modulating nutrients; IMN) may help prevent the development and progression of atherosclerosis, the main disease process underlying peripheral artery disease (PAD). Currently, no screening tool exists to measure IMN intake; therefore, the aim of this project is to develop and validate a short food frequency questionnaire (FFQ) that measures dietary intake of 14 nutrients with proposed immune-modulating effects, identified by the literature (copper, iron and zinc, vitamins A, C, D and E, alpha linolenic acid, total long-chain omega-3 fatty acids, arginine, glutamic acid, isoleucine, leucine and valine) in patients with established PAD. A 21-item FFQ was developed to measure average daily intake of IMNs over the past 12 months. Participants (n = 106) were recruited from Flinders Medical Centre, where they completed the FFQ followed by the reference method, a diet history reflecting usual intake over the past week. The mean age of participants was 72 years, with 83% being male (n = 88). Bland-Altman analysis resulted in a statistically non-significant p-value (p-value > 0.05) for 12 out of 14 nutrients, demonstrating good agreement between the two methods. Additionally, over 50% of nutrients had a sensitivity or specificity >70%. Consequently, the novel 21-item FFQ was determined to be a promising measure of dietary intake of 14 IMNs in patients with PAD when compared to the reference method of a diet history, and it is recommended that further investigations of the utility against biomarkers be explored in the future.

Effect of Dietary or Supplemental Vitamin C Intake on Vitamin C Levels in Patients with and without Cardiovascular Disease: A Systematic Review.

Atherosclerosis is a pro-oxidative and pro-inflammatory disease state, which is the underlying cause of most cardiovascular events, estimated to affect 5.2% of the Australian population. Diet, and specifically vitamin C, through its antioxidant properties can play a role in impeding the development and progression of atherosclerosis. This systematic review conducted comprehensive searches in Medline, Emcare, Scopus, PubMed, and Cochrane using key search terms for vitamin C, plasma vitamin C, supplementation, and cardiovascular disease (CVD). The results demonstrated that vitamin C supplementation resulted in a significant increase in vitamin C levels in populations with or without CVD, except for one study on the CVD population. It was also seen that the healthy population baseline and post-intervention vitamin C levels were high compared to the CVD population. However, further research is indicated for CVD population groups with varying baseline vitamin C levels, such as low baseline vitamin C, within a more representative elderly cohort in order to formulate and update vitamin C repletion guidelines.

Nutritional Considerations for Peripheral Arterial Disease: A Narrative Review.

Those with peripheral arterial disease (PAD) require important considerations with respect to food and nutrition, owing to advanced age, poor diet behaviours and immobility associated with the disease process and co-morbid state. These considerations, coupled with the economic effectiveness of medical nutrition therapy, mandate that dietetic care plays a vital role in the management of PAD. Despite this, optimising dietetic care in PAD remains poorly understood. This narrative review considers the role of medical nutrition therapy in every stage of the PAD process, ranging from the onset and initiation of disease to well established and advanced disease. In each case, the potential benefits of traditional and novel medical nutrition therapy are discussed.

Cost-effectiveness of individualized nutrition and exercise therapy for rehabilitation following hip fracture.

OBJECTIVE: To undertake a cost-utility analysis of the Individual Nutrition Therapy and Exercise Regime: A Controlled Trial of Injured, Vulnerable Elderly (INTERACTIVE) trial. DESIGN: Cost-utility analysis of a randomized controlled trial. SUBJECTS: A total of 175 patients following a hip fracture were allocated to receive either alternate weekly visits from a physical therapist and dietitian (intervention group), or social visits for 6 months (control group). METHODS: Costs for utilization of hospitals, health and community services were compared with quality-adjusted life years gained, calculated from responses to the Assessment of Quality of Life instrument. RESULTS: There were minimal differences in mean costs between the intervention ($AUD 45,331 standard deviation (SD): $AUD 23,012) and the control group ($AUD 44,764 SD: $AUD 20,712, p = 0.868), but a slightly higher mean gain in quality-adjusted life years in the intervention group (0.155, SD: 0.132) compared with the control group (0.139, SD: 0.149, p = 0.470). The incremental cost-effectiveness ratio was $AUD 28,350 per quality-adjusted life year gained, which is below the implied cost-effectiveness threshold utilized by regulatory authorities in Australia. CONCLUSION: A comprehensive 6-month programme of therapy from dietitians and physical therapists could be provided at a relatively low additional cost in this group of frail older adults, and the incremental cost-effectiveness ratio indicates likely cost-effectiveness, although there was a very high level of uncertainty in the findings.

Do Medications Commonly Prescribed to Patients with Peripheral Arterial Disease Have an Effect on Nutritional Status? A Review of the Literature.

BACKGROUND: Polypharmacy is common among patients with peripheral arterial disease (PAD) with a combination of medications used for risk-factor modification and medical management of the disease itself. Interaction between commonly prescribed medications and nutritional status has not previously been well described. This review aims to critically appraise evidence exploring associations between medications commonly prescribed to patients with PAD and nutritional status and provide recommendations for practice. METHODS: A comprehensive literature search was conducted to locate studies relating to nutrient interactions among lipid-lowering, antihypertensive, antiplatelet, and oral hypoglycemic drug classes. Quality of the evidence was rated on the basis of recommendations by the National Health and Medical Research Council. RESULTS: A total of 25 articles were identified as suitable and included in the review. No studies were specific to patients with PAD, and hence findings highlighting risk of ubiquinone (coenzyme Q10 [CoQ10]) depletion with lipid-lowering medications, zinc depletion with antihypertensive medications, and vitamin B12 depletion with oral hypoglycemic medications are extrapolated from heterogeneous groups of patients and healthy adults. The body of evidence ranged in quality from satisfactory to poor. CONCLUSIONS: High-quality research is required to confirm the interactions suggested by the included studies in patients with PAD specifically. It is, however, recommended that patients with PAD that are long-term consumers of the selected medications are monitored for CoQ10, zinc, and vitamin B12 to facilitate early identification of deficiencies and initiation of treatment. Treatment may involve dietary intervention and/or supplementation.

Validation of a Brief Dietary Assessment Tool for Estimating Dietary EPA and DHA Intake in Australian Adults at Risk of Cardiovascular Disease.

BACKGROUND: Short food frequency questionnaires (FFQs) are powerful screening instruments for estimating nutrient intakes and play an important role in risk stratification in vulnerable populations. Omega-3 fatty acids are of increasing importance in the prevention of chronic and degenerative disease, especially in older adults who are at higher risk of these chronic conditions. A short FFQ exists to rapidly assess omega-3 intake from marine sources, however it has not previously been validated for agreement with total omega-3 intake and ability to identify suboptimal omega-3 intakes in older adults or for use in Australia. OBJECTIVE: The aim of the study was to validate a 9-item marine omega-3 FFQ (MFQ) for assessment of omega-3 intake against a validated 74-item semiquantitative FFQ. METHODS: One hundred and eight participants (mean age 67 ± 10 years, 47% male) completed the MFQ designed to estimate omega-3 intake from marine sources and the 74-item FFQ designed to estimate usual omega-3 and total energy intake in addition to other nutrients. To test agreement between the two questionnaires for estimating total omega-3 intake, mean bias and 95% limits of agreement (LOA) were calculated. Sensitivity and specificity were assessed using 2 × 2 contingency tables based on whether participants did or did not meet National Heart Foundation (NHF) recommendations for omega-3 intake per day. RESULTS: Mean intake of omega-3 estimated from the MFQ was 210 ± 235 mg/day compared with 295 ± 260 mg/day as estimated by the FFQ. Mean bias (95% LOA) for omega-3 assessed by the two questionnaires was 89 mg/day (-475 mg to 653 mg). The MFQ achieved 98% sensitivity and 31% specificity for the omega-3 cut-off of 500 mg/day. When nutrient composition of the marine products were replaced with Australian data, mean intake of omega-3 was 230 ± 253 mg and the mean bias improved to 64 mg (-681 mg to 553 mg) and achieved 93% sensitivity and 40% specificity. CONCLUSIONS: The MFQ shows promise as a rapid screening tool for identifying older adults with intakes of omega-3 fatty acids likely to be below recommendations for chronic and degenerative disease risk reduction. Given the clinically meaningful mean bias and wide LOA, it cannot be recommended as an appropriate tool for the purpose of reporting average intake of individuals. Use of Australian nutrient data improved the mean bias of the tool in estimating total omega-3 intake. The values should be replaced and the MFQ could then be a useful tool for research purposes at the population level.

Fish oil administration in older adults: is there potential for adverse events? A systematic review of the literature.

BACKGROUND: Omega-3 (n-3) fatty acid supplementation is becoming increasingly popular. However given its antithrombotic properties the potential for severe adverse events (SAE) such as bleeding has safety implications, particularly in an older adult population. A systematic review of randomized control trials (RCT) was conducted to explore the potential for SAE and non-severe adverse events (non-SAE) associated with n-3 supplementation in older adults. METHODS: A comprehensive search strategy using Medline and a variety of other electronic sources was conducted. Studies investigating the oral administration of n-3 fish oil containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or both against a placebo were sourced. The primary outcome of interest included reported SAE associated with n-3 supplementation. Chi-square analyses were conducted on the pooled aggregate of AEs. RESULTS: Of the 398 citations initially retrieved, a total of 10 studies involving 994 older adults aged ≥60 years were included in the review. Daily fish oil doses ranged from 0.03 g to 1.86 g EPA and/or DHA with study durations ranging from 6 to 52 weeks. No SAE were reported and there were no significant differences in the total AE rate between groups (n-3 intervention group: 53/540; 9.8%; placebo group: 28/454; 6.2%; p = 0.07). Non-SAE relating to gastrointestinal (GI) disturbances were the most commonly reported however there was no significant increase in the proportion of GI disturbances reported in participants randomized to the n-3 intervention (n-3 intervention group: 42/540 (7.8%); placebo group: 24/454 (5.3%); p = 0.18). CONCLUSIONS: The potential for AEs appear mild-moderate at worst and are unlikely to be of clinical significance. The use of n-3 fatty acids and the potential for SAE should however be further researched to investigate whether this evidence is consistent at higher doses and in other populations. These results also highlight that well-documented data outlining the potential for SAE following n-3 supplementation are limited nor adequately reported to draw definitive conclusions concerning the safety associated with n-3 supplementation. A more rigorous and systematic approach for monitoring and recording AE data in clinical settings that involve n-3 supplementation is required.

A systematic review to evaluate the effectiveness of carnitine supplementation in improving walking performance among individuals with intermittent claudication.

OBJECTIVE: To evaluate the evidence for the use of carnitine supplementation in improving walking performance among individuals with intermittent claudication. DESIGN: Systematic review. METHODS: An electronic search of the literature was performed using MEDLINE (PubMed), Scopus, Cochrane Central Register of Controlled Trials and The Cochrane Library from inception through to November 2012. Search terms included peripheral arterial disease, intermittent claudication and carnitine. Reference lists of review articles and primary studies were also examined. Full reports of published experimental studies including randomized controlled trials and pre-test/post-test trials were selected for inclusion. A quality assessment was undertaken according to the Jadad scale. RESULTS: A total of 40 articles were retrieved, of which 23 did not meet the inclusion criteria. The 17 included articles reported on a total of 18 experimental studies of carnitine supplementation (5 pre-test/post-test; 8 parallel RCT; 5 cross-over RCT) for improving walking performance in adults with intermittent claudication. For pre-test/post-test studies, 300-2000 mg propionyl-L-carnitine (PLC) was administered orally or intravenously for a maximum of 90 days (7-42 participants) with statistically significant improvements of between 74 m and 157 m in pain free walking distance and between 71 m and 135 m in maximal walking distance across 3 out of 5 studies. Similarly, PLC (600 mg-3000 mg) was administered orally in 7 out of 8 parallel RCTs (22-485 participants), the longest duration being 12 months. All but one of the smallest trials demonstrated statistically significant improvements in walking performance between 31 and 54 m greater than placebo for pain free walking distance and between 9 and 86 m greater than placebo for maximal walking distance. A double-blind parallel RCT of cilostazol plus 2000 mg oral L-carnitine or placebo for 180 days (145 participants) did not demonstrate any significant improvement in walking performance. Of 5 cross-over RCTs (8-20 participants), 4 demonstrated significant improvements in walking performance following administration of 300-6000 mg L-carnitine or PLC. Compared to placebo, pain free walking distance and maximal walking distance improved by 23-132 m and 104 m respectively following carnitine intervention. CONCLUSIONS: Most trials demonstrated a small or modest improvement in walking performance with administration of PLC or L-carnitine. These findings were largely independent of level or quality of evidence, while there was some evidence that intravenous administration was more effective than oral administration and those with severe claudication may achieve greater benefits than those with moderate claudication. Routine carnitine supplementation in the form of PLC may therefore be a useful adjunct therapy for management of intermittent claudication. Further research is warranted to determine the optimal form, duration, dose and safety of carnitine supplementation across the spectrum of peripheral arterial disease severity and its effect with concurrent supervised exercise programs and best medical therapy. These studies should be supplemented with cost effectiveness studies to ensure that the return on the investment is acceptable.

Testing the acceptability of liquid fish oil in older adults.

Inflammatory conditions likely to benefit from fish oil therapy are prevalent in older adults however acceptability in this group is uncertain. This study aimed to assess the palatability of a range of liquid fish oil concentrations, the frequency and extent of side effects, and to summarise any effects on adherence to fish oil therapy in older adults. One hundred patients (>=60 years) completed a randomised, single-blind palatability study, conducted in two parts. In part one, 50 subjects, blinded to random sample order, consumed multiple liquid fish oil samples (2x10%, 40% and 100%). In part two, 50 subjects tasted one concentration, or 100% extra light olive oil (control). Pleasantness of taste was scored on a 5-point Likert scale. Side effects were recorded 24-hr post-tasting. Results of part one showed that 9/50 participants reported increasingly unpleasant taste with increasing fish oil concentration. 14/50 reported unpleasant taste for 100% fish oil vs 7/50 for 10%. 14/50 reported side effects which would not affect compliance with therapy. For part two, 1/12 reported unpleasant taste for 100% vs 0/13 for 10% fish oil or control. 4/50 reported side effects and 2/4 indicated these would prevent ongoing fish oil therapy. The authors conclude that taste itself is not a deterrent to fish oil therapy. Furthermore, reported adverse effects may not be a true reaction to fish oil, or dissuade patients from compliance. Liquid fish oil supplements are acceptable to older adults, therefore should be investigated as a therapy for geriatric conditions.

A trial assessing N-3 as treatment for injury-induced cachexia (ATLANTIC trial): does a moderate dose fish oil intervention improve outcomes in older adults recovering from hip fracture?

BACKGROUND: Proximal femoral fractures are associated with increased morbidity and mortality. Pre-existing malnutrition and weight loss amongst this patient group is of primary concern, with conventional nutrition support being largely ineffective. The inflammatory response post proximal femoral fracture surgery and the subsequent risk of cachexia may explain the inability of conventional high energy high protein management to produce an anabolic response amongst these patients. Omega-3 fatty acids derived from fish oils have been extensively studied for their anti-inflammatory benefits. Due to their anti-inflammatory properties, the benefit of fish oil combined with individualized nutrition support amongst proximal femoral fracture patients post surgery is an attractive potential therapeutic strategy. The aim of the ATLANTIC trial is to assess the potential benefits of an anti-inflammatory dose of fish oil within the context of a 12 week individualised nutrition program, commencing seven days post proximal femoral fracture surgery. METHODS/DESIGN: This randomized controlled, double blinded trial, will recruit 150 community dwelling elderly patients aged ≥65 years, within seven days of surgery for proximal femoral fracture. Participants will be randomly allocated to receive either a 12 week individualized nutrition support program complemented with 20 ml/day anti-inflammatory dose fish oil (~3.6 g eicosapentaenoic acid, ~2.4 g docosahexanoic acid; intervention), or, a 12 week individualized nutrition support program complemented with 20 ml/day low dose fish oil (~0.36 g eicosapentaenoic acid, ~0.24 g docosahexanoic acid; control). DISCUSSION: The ATLANTIC trial is the first of its kind to provide fish oil combined with individualized nutrition therapy as an intervention to address the inflammatory response experienced post proximal femoral fracture surgery amongst elderly patients. The final outcomes of this trial will assist clinicians in the development of effective and alternative treatment methods post proximal femoral fracture surgery which may ultimately result in a reduction in systemic inflammation, loss of weight and lean muscle and improvements in nutritional status, mobility, independence and quality of life among elderly patients. TRIAL REGISTRATION: ACTRN12609000241235.

Individual nutrition therapy and exercise regime: a controlled trial of injured, vulnerable elderly (INTERACTIVE trial).

BACKGROUND: Proximal femoral fractures are amongst the most devastating consequences of osteoporosis and injurious accidental falls with 25-35% of patients dying in the first year post-fracture. Effective rehabilitation strategies are evolving however, despite established associations between nutrition, mobility, strength and strength-related functional outcomes; there has been only one small study with older adults immediately following fragility fracture where a combination of both exercise and nutrition have been provided. The aim of the INTERACTIVE trial is to establish whether a six month, individualised exercise and nutrition program commencing within fourteen days of surgery for proximal femur fracture, results in clinically and statistically significant improvements in physical function, body composition and quality of life at an acceptable level of cost and resource use and without increasing the burden of caregivers. METHODS AND DESIGN: This randomised controlled trial will be performed across two sites, a 500 bed acute hospital in Adelaide, South Australia and a 250 bed acute hospital in Sydney, New South Wales. Four hundred and sixty community-dwelling older adults aged > 70 will be recruited after suffering a proximal femoral fracture and followed into the community over a 12-month period. Participants allocated to the intervention group will receive a six month individualised care plan combining resistance training and nutrition therapy commencing within 14 days post-surgery. Outcomes will be assessed by an individual masked to treatment allocation at six and 12 months. To determine differences between the groups at the primary end-point (six months), ANCOVA or logistic regression will be used with models adjusted according to potential confounders. DISCUSSION: The INTERACTIVE trial is among the first to combine nutrition and exercise therapy as an early intervention to address the serious consequence of rapid deconditioning and weight loss and subsequent ability to regain pre-morbid function in older patients post proximal femoral fracture. The results of this trial will guide the development of more effective rehabilitation programs, which may ultimately lead to reduced health care costs, and improvements in mobility, independence and quality of life for proximal femoral fracture sufferers. TRIAL REGISTRATION: Australian Clinical Trials Registry: ACTRN12607000017426.

Adherence to nutrition supplements among patients with a fall-related lower limb fracture.

BACKGROUND: The purpose of this study was to provide a detailed evaluation of adherence to nutrition supplements by patients with a lower limb fracture. METHODS: These descriptive data are from 49 nutritionally "at-risk" patients aged 70+ years admitted to the hospital after a fall-related lower limb fracture and allocated to receive supplementation as part of a randomized, controlled trial. Supplementation commenced on day 7 and continued for 42 days. Prescribed volumes aimed to meet 45% of individually estimated theoretical energy requirements to meet the shortfall between literature estimates of energy intake and requirements. The supplement was administered by nursing staff on medication rounds in the acute or residential care settings and supervised through thrice-weekly home visits postdischarge. RESULTS: Median daily percent of the prescribed volume of nutrition supplement consumed averaged over the 42 days was 67% (interquartile range [IQR], 31-89, n = 49). There was no difference in adherence for gender, accommodation, cognition, or whether the supplement was self-administered or supervised. Twenty-three participants took some supplement every day, and a further 12 missed <5 days. For these 35 "nonrefusers," adherence was 82% (IQR, 65-93), and they lost on average 0.7% (SD, 4.0%) of baseline weight over the 6 weeks of supplementation compared with a loss of 5.5% (SD, 5.4%) in the "refusers" (n = 14, 29%), p = .003. CONCLUSIONS: We achieved better volume and energy consumption than previous studies of hip fracture patients but still failed to meet target supplement volumes prescribed to meet 45% of theoretical energy requirements. Clinicians should consider alternative methods of feeding such as a nasogastric tube, particularly in those patients where adherence to oral nutrition supplements is poor and dietary intake alone is insufficient to meet estimated energy requirements.