1. Introduction
Globally, significant gains in human longevity have been made in the last couple of decades as evidenced by an average 5.5-year increase in life expectancy between 2000 and 2016 [1]. In many countries average life expectancy currently exceeds 80 years [1]. These longevity gains have come at a cost, however, with the most obvious being an increase in age-related diseases [2]. Noncommunicable diseases (NCDs) such as diabetes, musculoskeletal disorders, cardiovascular diseases, neurological disorders, and cancers increase with age, and place a burden on individuals and healthcare systems [3].
The WHO estimates that NCDs contribute 1.6 billion disability-adjusted life-years (DALYs) to the global burden of disease and identified unhealthy diets and physical inactivity are among the main modifiable risk factors, together with excess alcohol and tobacco use [6].
Modern lifestyles and easy access to high-energy, low-nutrient rich foods are considered part of the problem [3,10,11,12]. For example, the economic costs of unhealthy diets and low physical activity in the EU were calculated to be €1.3 billion per year [13].
Currently, health authorities mainly target problems associated with obesity and cardiovascular diseases by focusing on reducing excess intake of calories, sugar, salt, and saturated fats. However, the importance of a positive message associated with promoting adequate nutrient intake as part of a balanced diet should not be overlooked [4].
There is considerable variation in the consumption of food items that need to be encouraged and food items which should be limited, both between and within different countries. This was reflected in a recent study in European countries showing suboptimal nutrient-density of diets and significant proportions of the population consuming excess amounts of salt, sugar and saturated fat, as well as significant proportions of the population not meeting the required or adequate intakes for various essential nutrients (Table 1) [12].
An estimated 5% to 10% of community-dwelling adults >70 years of age are undernourished; this proportion rises to 30% to 65% among institutionalized elderly patients. In the older adult population, nutrients of concern include, among others, calcium, vitamin D, and vitamin B6 and B12 [15,20,21]. Vitamin D deficiency was found not only to be a problem in the elderly, but to be a global problem common across all age ranges [22].
In general, activities endorsing lifestyles that include healthy diets have usually focused on limiting the consumption of salt, sugar, and saturated fat. However, focus on the need to meet adequate dietary intake of essential nutrients through a healthy diet is considered equally important.
2. Musculoskeletal Health in the Older Adult
In a WHO report it was noted that the remaining lifetime risk of an osteoporotic fracture in women aged 50 years in developed countries was >40% (>20% for hip fracture) [27]. At the time of this report, osteoporotic fractures had the sixth highest disease burden in the Americas and Europe combined, as estimated by disability-adjusted life years [27,28].
In the elderly, both micronutrient and macronutrient deficiencies appear to contribute to the pathogenesis of skeletal fractures as a consequence of age-related bone loss and frailty [16]. Nutrients that play a role in bone metabolism include vitamin D and vitamin K, calcium, magnesium, phosphorus, proteins, and fatty acids.
2.1. Vitamin D in Musculoskeletal Health
Low vitamin D levels have been mainly implicated in musculoskeletal disorders including bone and muscle health [29].
Serum 25-hydroxyvitamin D is the most widely used indicator for vitamin D status in clinical practice and, while 25–50 nmol/L is generally defined as insufficiency with regards to bone health, for optimal calcium absorption and control of secondary hyperparathyroidism a level closer to 75 nmol/L has been proposed [16,22,32,33]. Most researchers agree that 25-hydroxyvitamin D levels below 50 nmol/L are associated with lower bone mineral density [22]. Likewise, the effect of vitamin D deficiency on fracture risk is difficult to quantify, but large population studies found that hip fracture risk was higher in those with a 25-hydroxyvitamin D level below 50–62.5 nmol/L [34,35]. Based on a serum 25-hydroxyvitamin D level of <30 nmol/L it was reported that on average 13% of 55,844 European individuals had moderate or severe vitamin D deficiency, and this increased to 40% of individuals with mild to severe deficiency if a level of <50 nmol/L was included [36]. The authors noted that vitamin D deficiency was present across Europe and was both a clinical and public health concern requiring urgent action. Similar levels of vitamin D deficiency and concern have been reported by many research groups worldwide [22,36,37,38].
The role of vitamin D and related analogues, with or without calcium, for preventing bone fractures in post-menopausal women and older men was the subject of a Cochrane review [25]. This systematic review included 53 trials and 91,791 older women or men aged over 65 years from community, hospital, and nursing-home settings, and assessed the impact of vitamin D for the prevention of hip or other types of fracture. In this analysis vitamin D alone did not appear to have a significant effect on fracture prevention, whereas vitamin D in combination with calcium significantly reduced the likelihood of hip fractures (P = 0.01), non-vertebral fractures and any type of fracture. Hip fracture incidence was particularly reduced in institutionalized residents with a risk reduction of 25%.
2.2. Vitamin K in Musculoskeletal Health
Two forms of vitamin K exist: vitamin K1 (phylloquinone, mainly found in green leafy vegetables) and vitamin K2 (menaquinone, mainly found in fermented dairy and produced by lactic acid bacteria in the intestine). Vitamin K is required for promoting osteoblast differentiation, upregulating transcription of specific genes in osteoblasts, and activating bone-associated vitamin K dependent proteins, which play critical roles in extracellular bone matrix mineralization. Less is known about vitamin K and health, but there is growing evidence suggesting a synergistic effect between vitamins K and D in bone [40].
Vitamin K2 supplementation combined with vitamin D and calcium for 2 years in a randomized placebo-controlled trial resulted in a significant increase in bone-mineral density and content in older women [42]. In another recent RCT it was found that combined vitamin K2, vitamin D and calcium supplementation for 6 months increased the bone mineral density of lumbar 3 spine vertebra compared to vitamin D and calcium alone in postmenopausal Korean women [43].
3. Cognitive Disorders
Dementia is a term that describes a decline in cognitive abilities including memory, and reduction in a person’s ability to perform everyday activities [44]. Dementia prevalence is forecast to increase dramatically in future years [45]. At present about 50 million people have dementia worldwide, and this is projected to reach 80 million by 2030 and 150 million by 2050 [46]. Alzheimer’s disease (AD) is the most common form of dementia in people aged >60 years, accounting for 60–70% of the total number of cases and is the major focus of this section [46]. Vascular dementia is the second most common cause of dementia with at least 20% of dementia cases.
With respect to dementia, there is reasonable evidence linking lower levels of folic acid, vitamin B6, vitamin B12, and higher concentrations of homocysteine with age-related cognitive decline [50]. One of the mechanisms involved may the impaired methylation processes due to folic acid and vitamin B12 deficiency that lead to accumulation of homocysteine affecting mood and some cognitive functions [50]. In several RCTs supplementation with folic acid, vitamin B12, and vitamin B6 for at least 2 years has been investigated [44]. However, the findings of a recent meta-analysis reported that B vitamins had little to no effect with respect to preventing cognitive decline [51].
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Trials that have reported no effect of nutrients generally included older adults who were unlikely to have a marked decline in cognitive function [52]. Trial design should consider including older individuals with deficiencies that increases their risk of cognitive decline, and who may benefit from nutrition intervention.
4. Eye Disorders
Impairments of the essential senses of vision and hearing are the second-leading cause of years of lived with disability [58]. The most common causes of vision loss among the elderly are age-related macular degeneration, glaucoma, cataracts, and diabetic retinopathy [59]. Aging is the greatest risk factor associated with the development of age-related macular degeneration, but also environmental and lifestyle factors such as smoking, oxidative stress, and diet may significantly affect the risk [60].
Carotenoids have a range of functions in human health and, in particular, there is evidence that they have beneficial effects on eye health [62]. Two dietary carotenoids, lutein and zeaxanthin are macular pigments found in the human retina [63]. Macular pigment has local antioxidant properties and absorbs high energy, short wavelength blue light protecting the retina from photochemical damage [64]. Macular pigment can neutralize ROS, protect against UV-induced peroxidation, and reduce the formation of lipofuscin and associated oxidative-stress induced damage [63]. Thus, the carotenoids provide potential benefits for ocular function and health.
Individuals who have low macular pigment optical density levels (0.2 or lower) may benefit from supplementation with lutein/zeaxanthin which can help increase macular pigment optical density levels [65,66,67,68,69,70,71,72]. For retinal protection, macular pigment optical density values of 0.4 to 0.6 are desirable, especially in older adults [73].
Age-related macular degeneration is an increasing problem among the elderly and studies of the effects of lutein/zeaxanthin supplementation have produced mixed results. However, important data were provided by secondary analyses of the large Age-Related Eye Disease Study 2 (AREDS2) [77,78]. This randomized trial investigated the effect of adding lutein/zeaxanthin 10/2 mg, DHA (350 mg) + EPA (650 mg), or both to the original AREDS2 formulation (vitamin C, vitamin E, β-carotene, zinc, and copper) or to variations of this formulation (excluding β-carotene and/or with reduced zinc). Participants (n = 4203) were followed for a median 5 years. The primary analysis found no additional beneficial or harmful effect for lutein/zeaxanthin and/or omega-3 fatty acids on progression to late age-related macular degeneration compared with the original AREDS1 formula using β-carotene instead of lutein/zeaxanthin. However, a prespecified secondary analysis found a significant 26% risk reduction for progression to advanced age-related macular degeneration when comparing lutein/zeaxanthin supplementation with no lutein/zeaxanthin supplementation in the quintile with the lowest dietary intake of these two carotenoids (median 0.7 mg/day), as indicated by a hazard ratio of 0.74 (95% confidence interval 0.59–0.94, p = 0.01). In addition, a post hoc analysis showed that lutein/zeaxanthin (excluding β-carotene) was more effective than the original AREDS formulation containing β-carotene but no lutein/zeaxanthin for reducing progression to advanced age-related macular degeneration (hazard ratio 0.82, 95% CI 0.69–0.96, p = 0.02) [77].
If the AREDS2 complex (i.e., vitamin C and E, zinc, copper, lutein/zeaxanthin and omega-3 fatty acids) was used by all adults aged >55 years, it has been estimated this would result in an average of about 1 million avoided age-related macular degeneration and cataract events per year in the USA (based on a risk reduction of 23.6% for age-related macular degeneration and 16.2% for cataracts). This would result in a net annual cost saving of US$1.2 billion, mostly as a consequence of reduced healthcare expenditure [81].
5. Cardiovascular Disease
Despite the global decline in cardiovascular mortality, cardiovascular diseases remain the leading cause of morbidity and mortality, contributing to escalating health care cost [82].
Good nutrition plays an important role in delaying the progression of cardiovascular disease [85,86]. The adverse effects of excess intakes of saturated and trans fats, cholesterol, added sugars, and salt in relation to cardiovascular disease progression has been relatively well-established whereas the effect of addressing inadequate essential nutrients is less well-known.
5.1. Cardiovascular Events
5.1.1. Diets
Lifestyle changes, including dietary modifications, are recommended as part of the management strategy to improve lipid profiles and reduce the risk of cardiovascular disease [89,90,91]. The primary emphasis of dietary interventions has been on changing dietary macronutrient and salt composition. The effect of improving micronutrient-richness of the diet in cardiovascular disease control has been less-well studied. A diet rich in fruits, vegetables, wholegrains, legumes, nuts, fish, poultry, and low-fat dairy products, and limited consumption of red meat, saturated fat, and added sugar is advocated, mostly based on positive associations with cardiovascular health [89,90,91]. Dietary patterns that follow these principles include the Dietary Approaches to Stop Hypertension (DASH) diet, a diet rich in fiber, protein, magnesium, calcium, and potassium, and low in total and saturated fats, which has been shown to reduce low-density lipoprotein (LDL)-cholesterol levels [91], and the Mediterranean diet, which has been shown to reduce the risk for cardiovascular disease in both primary and secondary settings [92,93]. Regression of coronary artery atherosclerosis has been demonstrated with a program of intensive lifestyle changes that included a vegetarian diet, exercise, and smoking cessation [94].
5.1.2. Vitamin D
5.1.3. B-Vitamins
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A more recent meta-analysis of folic acid supplementation (30 RCTs, 82,334 participants) estimated a 10% lower risk of stroke and a 4% lower risk of overall cardiovascular disease compared with controls [102]. The greatest benefit for cardiovascular disease was observed in individuals with lower plasma folate levels at baseline and without pre-existing cardiovascular disease (p = 0.006 for both). While patients with a cardiovascular disease history responded to B-vitamins with normalization of homocysteine levels, those with the MTHFR 677C > T genotype were less responsive and may have greater folate requirements than do their counterparts [103].
5.1.4. Vitamin K
5.1.5. Omega-3 LCPUFA
5.1.6. Antioxidants
5.1.7. Vitamin E
5.1.8. Phenolics
Phenolic compounds are bioactive compounds found in plants, and there is evidence that some may be helpful for reducing cardiovascular risk factors [116]. Flavonoids are polyphenolic compounds found in fruits, vegetables, tea, and red wine [116].
5.2. Hypertension
5.2.1. Diets
Diets with a high nutritional value, such as the traditional Mediterranean diet, DASH and the OmniHeart (a variation of DASH with increased levels of protein) diets, can be important steps on the path to weight loss, lowering blood pressure, and prevention of hypertension [125]. The benefits of the DASH diet on blood pressure were reported in a RCT with all participants receiving graded amounts of sodium (high, intermediate, low). There were dose-response decreases in systolic and diastolic blood pressures, and age-related increases in blood pressure were blunted [128].
5.2.2. Milk peptides
A meta-analysis of 14 RCTs involving 1306 European subjects found that the milk-derived lactotripeptides isoleucine-proline-proline and valine-proline-proline produced small and statistically significant reductions in mean systolic blood pressure and diastolic blood pressure [130]. The authors noted that a similar effect had been seen in Asian populations.
5.2.3. Omega-3 LCPUFAs
5.2.4. Vitamin C
5.2.5. Vitamin D
In a study involving 283 hypertensive patients, vitamin D3 (cholecalciferol) produced a modest but statistically significant reduction in systolic blood pressure compared with placebo after 3 months [134]. There was no significant effect on diastolic blood pressure.
5.2.6. Flavonols
5.3. Diabetes
5.3.1. Vitamin D
A recent meta-analysis [137] including a total of 20 RCTs and 2703 participants, found that vitamin D supplementation was associated with elevated serum vitamin D levels and significantly decreased insulin resistance. Changes in other parameters such as fasting blood glucose and hemoglobin A1c (HbA1c) were relatively small and did not achieve statistical significance [137].
5.3.2. Vitamin E
The RCTs in diabetes patients that retrospectively analyzed the data for the effect of vitamin in E found that administration of vitamin E lowered the risk of cardiovascular disease events by 34% and cardiovascular-related mortality by 53% among patients with the haptoglobin 2-2 genotype [140].
5.3.3. Omega-3 LCPUFA
5.3.4. Vitamin K
5.3.5. Chromium
Chromium plays a role in insulin metabolism by activating oligopeptide low-molecular-weight chromium (LMWCr)-binding substance and activating insulin-dependent kinase activity. A meta-analysis of the efficacy of chromium supplementation suggest that there is available evidence for chromium on glycemic control in patients with diabetes [144].
Referência :
(1) Nutrients. 2019 Jan 4;11(1):85.
