The effect of long chain omega-3 polyunsaturated fatty acids on muscle mass and function in sarcopenia: A scoping systematic review and meta-analysis.

BACKGROUND & AIMS: Sarcopenia is characterized by the progressive loss of skeletal muscle mass and function, which reduces mobility and quality of life. Risk factors for sarcopenia include advanced age, physical inactivity, obesity, and chronic diseases such as cancer or rheumatoid arthritis. Omega-3 long chain polyunsaturated fatty acids (LC PUFAs) might be associated with a reduction in risk of sarcopenia due to their anti-inflammatory effects. METHODS: We conducted a systematic review and meta-analysis to quantify the effects of omega-3 LC PUFAs on muscle mass, volume and function parameters. The National Library of Medicine's MEDLINE/PubMed database was searched on 9th October 2020 for randomized controlled trials that used omega-3 LC PUFAs as an intervention with muscle-related endpoints. A snowballing search to identify additional studies was completed on 23rd April 2021. The meta-analysis was conducted using meta-essentials worksheet 3. Bias was assessed using the Jadad scale. RESULTS: 123 studies were identified with the systematic searches. Most studies were performed in disease populations, such as cancer or chronic obstructive pulmonary disease (COPD), or in healthy individuals after a fatiguing exercise bout. The endpoints lean body mass, skeletal muscle mass, mid-arm muscle circumference, handgrip strength, quadriceps maximal voluntary capacity (MVC), and 1-repetition maximum chest press were selected for meta-analysis based on the number of available studies; thus 66 studies were included in the quantitative synthesis. Using a random effects model and 2-tailed p-value, there was a significant relationship in favor of omega-3 LC PUFA supplementation for lean body mass (effect size 0.27, 95%CI 0.04 to 0.51), skeletal muscle mass (effect size 0.31, 95%CI 0.01 to 0.60) and quadriceps MVC (effect size 0.47, 95%CI 0.02 to 0.93). CONCLUSION: The results indicate that there is a positive effect of omega-3 LC PUFA supplementation on overall body muscle mass and strength. Small study size and heterogeneity limit the applicability of these findings for sarcopenia prevention. Larger trials in populations at risk of sarcopenia would strengthen the evidence base.

Expert Opinion on Benefits of Long-Chain Omega-3 Fatty Acids (DHA and EPA) in Aging and Clinical Nutrition.

Life expectancy is increasing and so is the prevalence of age-related non-communicable diseases (NCDs). Consequently, older people and patients present with multi-morbidities and more complex needs, putting significant pressure on healthcare systems. Effective nutrition interventions could be an important tool to address patient needs, improve clinical outcomes and reduce healthcare costs. Inflammation plays a central role in NCDs, so targeting it is relevant to disease prevention and treatment. The long-chain omega-3 polyunsaturated fatty acids (omega-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are known to reduce inflammation and promote its resolution, suggesting a beneficial role in various therapeutic areas. An expert group reviewed the data on omega-3 LCPUFAs in specific patient populations and medical conditions. Evidence for benefits in cognitive health, age- and disease-related decline in muscle mass, cancer treatment, surgical patients and critical illness was identified. Use of DHA and EPA in some conditions is already included in some relevant guidelines. However, it is important to note that data on the effects of omega-3 LCPUFAs are still inconsistent in many areas (e.g., cognitive decline) due to a range of factors that vary amongst the trials performed to date; these factors include dose, timing and duration; baseline omega-3 LCPUFA status; and intake of other nutrients. Well-designed intervention studies are required to optimize the effects of DHA and EPA in specific patient populations and to develop more personalized strategies for their use.

Potential Links between Impaired One-Carbon Metabolism Due to Polymorphisms, Inadequate B-Vitamin Status, and the Development of Alzheimer's Disease.

Alzheimer's disease (AD) is the major cause of dementia and no preventive or effective treatment has been established to date. The etiology of AD is poorly understood, but genetic and environmental factors seem to play a role in its onset and progression. In particular, factors affecting the one-carbon metabolism (OCM) are thought to be important and elevated homocysteine (Hcy) levels, indicating impaired OCM, have been associated with AD. We aimed at evaluating the role of polymorphisms of key OCM enzymes in the etiology of AD, particularly when intakes of relevant B-vitamins are inadequate. Our review indicates that a range of compensatory mechanisms exist to maintain a metabolic balance. However, these become overwhelmed if the activity of more than one enzyme is reduced due to genetic factors or insufficient folate, riboflavin, vitamin B6 and/or vitamin B12 levels. Consequences include increased Hcy levels and reduced capacity to synthetize, methylate and repair DNA, and/or modulated neurotransmission. This seems to favor the development of hallmarks of AD particularly when combined with increased oxidative stress e.g., in apolipoprotein E (ApoE) ε4 carriers. However, as these effects can be compensated at least partially by adequate intakes of B-vitamins, achieving optimal B-vitamin status for the general population should be a public health priority.

Absorption studies show that phytase from Aspergillus niger significantly increases iron and zinc bioavailability from phytate-rich foods.

BACKGROUND: Iron and zinc deficiency are major public health problems affecting many parts of the world, including Southeast Asia. Infants, young children, and women of reproductive age are particularly vulnerable due to their high requirements. Even though iron and zinc are present in significant amounts in the plant-based diets typically consumed in developing countries, their bioavailability is low due to high levels of absorption inhibitors such as phytate. Phytase has been used in animal nutrition for decades to improve the bioavailability of certain minerals in feed. OBJECTIVE: To show the effect of phytase in human nutrition based on evidence from human studies. Phytase can be used either during processing or as an active food ingredient degrading dietary phytate during stomach transit time. METHODS: Evidence from human studies testing the effect of phytase on iron and zinc bioavailability using stable isotopes was reviewed. RESULTS: Twelve studies tested the effect of phytase on iron and five tested its effect on zinc bioavailability. Most of these studies used a phytase derived from Aspergillus niger. They found a beneficial effect unless phytate concentrations were too low or levels of inhibitors or enhancers of iron absorption were too high. Twenty to 320 phytase units per 100 g of flour significantly improved iron absorption, even though higher levels might further increase iron bioavailability. For zinc, not enough information is available to determine optimal activities. CONCLUSIONS: Phytase clearly has a beneficial effect on iron and zinc absorption from phytate-rich foods. It also has the potential to increase the absorption of magnesium, calcium, and phosphorus in areas such as Southeast Asia where mineral deficiencies are widespread.

The role of vitamins in aging societies.

Raising numbers of elderly lead to a dramatic shift in demographics, accompanied by an increase in non-communicable diseases such as cancer, cardiovascular disease and dementia. All these conditions are thought to be modifiable by diet to some degree and mounting evidence indicates that improved intakes of certain vitamins can slow their progress. Strong evidence exists for the beneficial effect of vitamin D on the risk of bone fractures. Moreover, as chromosomal damage is a risk factor for dementia, supplementation with nutrients preventing these impairments are thought to have a beneficial effect on cognitive decline. However, the aging progress strongly affects nutrient intakes and utilisation due to social, physical and psychological changes. Data from dietary surveys suggest that many of the elderly in Europe have intakes for various vitamins that are well below the recommendations. The situation appears to be even more critical for elderly in institutions such as care homes. Given the increasing number of elderly and the importance of an adequate supply with vitamins, more research is warranted to find nutritional solutions to improve their wellbeing and health - which in the long run can be expected to contribute to reduce the ever increasing health care costs.

Fortification iron as ferrous sulfate plus ascorbic acid is more rapidly absorbed than as sodium iron EDTA but neither increases serum nontransferrin-bound iron in women.

The absorption profile of iron fortificants may be a determinant of their ability to generate nontransferrin-bound iron (NTBI) and, thus, their potential safety. Ferrous iron may be absorbed more rapidly than chelated ferric iron, but differences at the fortification level cannot be distinguished with nonisotopically labeled serum iron curves. Using stable isotope appearance curves (SIAC) in serum, we measured iron absorption profiles from FeSO(4) with ascorbic acid (AA) and from NaFeEDTA, as well as the serum hepcidin and NTBI response following the meals. Healthy women (n = 16) were given 6 mg oral iron as labeled FeSO(4) and NaFeEDTA with a maize porridge using a crossover design. SIAC, NTBI, and serum hepcidin were measured over 8 h after the meal. Iron from FeSO(4) plus AA was more rapidly absorbed, resulting in a 35% greater relative AUC during the first 2 h than for NaFeEDTA (P < 0.001). Median (95% CI) fractional iron absorption from the FeSO(4)- and NaFeEDTA-fortified meals was 15.2% (11.0-19.5) and 6.0% (5.0-9.2), respectively (P < 0.001). In response to the FeSO(4)-fortified meal, there was an ~60% increase in median serum hepcidin (P < 0.05) but no significant change in NTBI. There was no significant change in serum hepcidin or NTBI after the NaFeEDTA-fortified meal. SIAC are a useful new tool to compare iron absorption profiles from different iron compounds in fortified foods. Even with the use of a very well absorbed ferrous iron compound, iron fortification in this population does not increase NTBI, suggesting a low risk for adverse health consequences.

A micronutrient powder with low doses of highly absorbable iron and zinc reduces iron and zinc deficiency and improves weight-for-age Z-scores in South African children.

Micronutrient powders (MNP) are often added to complementary foods high in inhibitors of iron and zinc absorption. Most MNP therefore include high amounts of iron and zinc, but it is no longer recommended in malarial areas to use untargeted MNP that contain the Reference Nutrient Intake for iron in a single serving. The aim was to test the efficacy of a low-iron and -zinc (each 2.5 mg) MNP containing iron as NaFeEDTA, ascorbic acid (AA), and an exogenous phytase active at gut pH. In a double-blind controlled trial, South African school children with low iron status (n = 200) were randomized to receive either the MNP or the unfortified carrier added just before consumption to a high-phytate maize porridge 5 d/wk for 23 wk; primary outcomes were iron and zinc status and a secondary outcome was somatic growth. Compared with the control, the MNP increased serum ferritin (P < 0.05), body iron stores (P < 0.01) and weight-for-age Z-scores (P < 0.05) and decreased transferrin receptor (P < 0.05). The prevalence of iron deficiency fell by 30.6% (P < 0.01) and the prevalence of zinc deficiency decreased by 11.8% (P < 0.05). Absorption of iron from the MNP was estimated to be 7-8%. Inclusion of an exogenous phytase combined with NaFeEDTA and AA may allow a substantial reduction in the iron dose from existing MNP while still delivering adequate iron and zinc. In addition, the MNP is likely to enhance absorption of the high native iron content of complementary foods based on cereals and/or legumes.

Plasma hepcidin is a modest predictor of dietary iron bioavailability in humans, whereas oral iron loading, measured by stable-isotope appearance curves, increases plasma hepcidin.

BACKGROUND: Plasma hepcidin appears to be a major regulator of iron absorption and homeostasis, but there are few data in humans. OBJECTIVES: With the use of iron stable isotopes, we aimed to determine whether circulating hepcidin predicts dietary iron bioavailability, to quantify the amount of absorbed iron after oral iron loading, and to measure the plasma hepcidin response. DESIGN: In the first study, young women (n = 98) with an iron status varying from iron deficiency anemia to iron sufficiency (women with serum ferritin concentrations 25-40 microg/L were not included) were given stable isotope-labeled test meals (n = 196) containing ferrous sulfate, ferrous fumarate, or ferric pyrophosphate, after which plasma hepcidin and iron bioavailability were measured. In the second study, iron-sufficient men (n = 4) were given 3.8- and 60-mg oral doses of labeled ferrous sulfate. The stable isotope appearance curve was determined, and the plasma hepcidin response was measured over 6 h. RESULTS: In study 1, plasma hepcidin and plasma ferritin were strongly correlated (r = 0.79, P < 0.001). Plasma hepcidin significantly, but modestly, predicted iron bioavailability from ferrous sulfate and ferrous fumarate (r = -0.51 and -0.46, respectively; P < 0.0001) but not from ferric pyrophosphate (r = -0.30, P = 0.056, respectively). In study 2, the 3.8-mg dose increased mean circulating absorbed iron to a peak of 0.42 micromol/L at 60 min but did not increase plasma hepcidin, The 60-mg dose increased mean circulating absorbed iron to a peak of 5.9 micromol/L at 120 min and produced an approximately 30% increase in mean plasma hepcidin at 6 h (P < 0.01). CONCLUSIONS: Plasma hepcidin is only a modest predictor of dietary iron bioavailability in humans. Oral iron loading, measured by stable-isotope appearance curves, increases circulating hepcidin.

Optimization of a phytase-containing micronutrient powder with low amounts of highly bioavailable iron for in-home fortification of complementary foods.

BACKGROUND: In-home fortification of complementary foods with micronutrient powders containing low amounts of iron may be potentially safer than powders containing high amounts of iron. However, low iron doses have little nutritional effect, unless iron absorption is high. OBJECTIVE: The objective was to maximize iron absorption from a low-iron micronutrient powder for in-home fortification by testing combinations of iron as NaFeEDTA, ascorbic acid, and a microbial phytase active at gut pH. In addition, a recently proposed enhancer of iron absorption, L-alpha-glycerophosphocholine (GPC), was tested. DESIGN: In 6 separate iron-absorption studies using a crossover design, women (n = 101) consumed whole-maize porridge fortified with 3 mg stable isotope-labeled FeSO4 or NaFeEDTA with different combinations of enhancers added to the meals at the time of consumption. Incorporation of iron isotopes into erythrocytes 14 d later was measured. RESULTS: The addition of phytase when iron was present as either NaFeEDTA or FeSO4, with or without ascorbic acid, significantly increased iron absorption. The combined addition of phytase, ascorbic acid, and NaFeEDTA resulted in an absorption of 7.4%, compared with an absorption of 1.5% from FeSO4 without enhancers in the same meal (P < 0.001). The addition of ascorbic acid did not significantly increase iron absorption from NaFeEDTA, and the addition of calcium did not significantly inhibit iron absorption from NaFeEDTA in the presence of ascorbic acid. The addition of L-alpha-glycerophosphocholine did not significantly increase iron absorption. CONCLUSION: Optimization of the micronutrient powder increased iron absorption from a highly inhibitory meal approximately 5-fold. This approach may allow for effective, untargeted in-home fortification of complementary foods with low amounts of highly bioavailable iron.