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EMAS position statement: Diet and health in midlife and beyond

      Abstract

      Introduction

      There is increasing evidence that life-style factors, such as nutrition, physical activity, smoking and alcohol consumption have a profound modifying effect on the epidemiology of most major chronic conditions affecting midlife health.

      Aims

      To provide guidance concerning the effect of diet on morbidity and mortality of the most frequent diseases prevalent in midlife and beyond.

      Materials and methods

      Literature review and consensus of expert opinion.

      Results and conclusions

      A healthy diet is essential for the prevention of all major chronic non-communicable diseases in midlife and beyond, both directly, through the effect of individual macro- and micronutrients and indirectly, through the control of body weight. Type 2 diabetes mellitus is best prevented or managed by restricting the total amount of carbohydrate in the diet and by deriving carbohydrate energy from whole-grain cereals, fruits and vegetables. The substitution of saturated and trans-fatty acids by mono-unsaturated and omega-3 fatty acids is the most important dietary intervention for the prevention of cardiovascular disease. Obesity is also a risk factor for a variety of cancers. Obese elderly persons should be encouraged to lose weight. Diet plans can follow the current recommendations for weight management but intake of protein should be increased to conserve muscle mass.
      The consumption of red or processed meat is associated with an increase of colorectal cancer. Adequate protein, calcium and vitamin D intake should be ensured for the prevention of osteoporotic fractures. Surveillance is needed for possible vitamin D deficiency in high risk populations. A diet rich in vitamin E, folate, B12 and omega-3 fatty acids may be protective against cognitive decline. With increasing longevity ensuring a healthy diet is a growing public health issue.

      Keywords

      1. Introduction

      Life expectancy is continuously increasing worldwide. In most European countries both men and women are expected to live beyond 80 years []. Longevity is the result of an improved socioeconomic environment and advanced medical care and is progressively leading to an aging society. This demography has shifted the etiology of morbidity and mortality from accidents, violence and infections toward chronic non-communicable diseases. In high-income countries, 9 out of the 10 leading causes of death fall into this category, most importantly cardiovascular disease, diabetes mellitus, cancer and dementia [

      WHO. Data and statistics. Available from: http://gamapserver.who.int/gho/interactive_charts/mbd/cod_2008/graph.html [accessed 30.08.12].

      ]. Life-style factors, such as nutrition, physical activity, smoking and alcohol consumption have a profound modifying effect on the epidemiology of most major chronic conditions affecting midlife health [
      • Loef M.
      • Walach H.
      The combined effects of healthy lifestyle behaviors on all cause mortality: a systematic review and meta-analysis.
      ]. The aim of this position statement is to summarize the evidence and to provide guidance concerning the effect of diet on morbidity and mortality of the most frequent diseases prevalent in midlife and beyond.

      2. Diet and morbidity in midlife and beyond

      2.1 Obesity

      Overweight and obesity are the result of in imbalance between energy intake and energy expenditure. This position statement focuses on the energy intake. Obesity is a major health epidemic worldwide. Despite public health interventions obesity figures continue to rise: currently there are 300 million obese adults worldwide, while half of the total global population is above normal weight [

      IASO. World map of obesity. Available from: http://www.iaso.org/resources/world-map-obesity/ [accessed 1.09.12].

      ]. Obesity, in particular central adiposity, reduces life expectancy in both sexes [
      • Chang S.H.
      • Beason T.S.
      • Hunleth J.M.
      • et al.
      A systematic review of body fat distribution and mortality in older people.
      ]; on the other hand centenarians are on average leaner compared to older adult controls [
      • Hausman D.B.
      • Fischer J.G.
      • Johnson M.A.
      Nutrition in centenarians.
      ]. Obesity is a strong risk factor for cardiovascular disease (CVD), diabetes mellitus, cancer, respiratory dysfunction, urinary incontinence, arthritis and dementia [
      • Han T.S.
      • Tajar A.
      • Lean M.E.
      Obesity and weight management in the elderly.
      ]. As a person grows older, however, body mass index (BMI) may not be representative of the adiposity status due to (a) decreasing height and (b) decreasing lean mass due to inactivity, hormonal decline or chronic medical conditions. Low lean mass, described as “sarcopenia”, may itself be a risk factor for morbidity and furthermore may mask increased central adiposity, particularly prevalent in the elderly [
      • Han T.S.
      • Tajar A.
      • Lean M.E.
      Obesity and weight management in the elderly.
      ]. This is the major factor contributing to the “obesity paradox”: while it is clear that obesity, as defined by high BMI, increases all-cause mortality in the general adult population, the evidence concerning the elderly is less convincing, with individuals in the range of overweight exhibiting better survival rates compared to persons with BMI < 25 [
      • Chang S.H.
      • Beason T.S.
      • Hunleth J.M.
      • et al.
      A systematic review of body fat distribution and mortality in older people.
      ].
      Obese elderly persons should be encouraged to lose weight. Diet plans should follow the current recommendations for weight management (low saturated fat, fat energy derived from mono- and polyunsaturated fat, carbohydrate energy derived from vegetable, fruits, beans, and whole-grain cereals, pasta or rice, protein energy derived mainly from fish, poultry, plants or skimmed dairy products) []. Management of elderly people, however, should differ from the general adult population with regard to the following points (1) indices of body composition and of central adiposity should be set as monitoring variables beyond BMI, (2) a higher proportion of protein should be incorporated as an energy source in daily caloric planning and (3) resistance exercise, tailored to the individual needs and abilities should be incorporated into the weight management program for the preservation of lean mass [
      • Li Z.
      • Heber D.
      Sarcopenic obesity in the elderly and strategies for weight management.
      ].

      2.2 Diabetes mellitus type 2

      Diabetes mellitus type 2 (DM2) accounts for 3% of all-cause mortality in the modern world and is a strong risk factor for cardiovascular disease, renal insufficiency, visual loss and neuropathy [

      WHO. Data and statistics. Available from: http://gamapserver.who.int/gho/interactive_charts/mbd/cod_2008/graph.html [accessed 30.08.12].

      ]. Weight reduction has a profound beneficial effect at all stages of developing DM2, namely metabolic syndrome, impaired glucose tolerance, impaired fasting glycemia as well as in the management of overt diabetes [
      • Dyson P.A.
      • Kelly T.
      • Deakin T.
      • et al.
      Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes.
      ]. Although high-carbohydrate/low fat diets were traditionally recommended to diabetics, it is increasingly being appreciated that low carbohydrate/high protein diets may offer a better long-term option concerning weight and metabolic control [
      • Arathuzik G.G.
      • Goebel-Fabbri A.E.
      Nutrition therapy and the management of obesity and diabetes: an update.
      ]. The most important aspect in prevention and management of DM2 is the restriction of the quantity of carbohydrates as energy source in the daily planning [
      • Franz M.J.
      • Boucher J.L.
      • Green-Pastors J.
      • et al.
      Evidence-based nutrition practice guidelines for diabetes and scope and standards of practice.
      ]. The fiber content of the diet, particularly insoluble fiber contained in whole grain cereals, has an inverse association with plasma glucose levels, insulin resistance and the risk of developing DM2 [
      • Ye E.Q.
      • Chacko S.A.
      • Chou E.L.
      • et al.
      Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain.
      ]. Possible mechanisms are the increased rate of passage through the GI tract, thus decreasing the absorption of macronutrients, the secretion of gastrointestinal insulinotropic hormones, the increase of satiety sense and finally the decrease of free fatty acids in the circulation resulting in augmented intracellular glucose transport [
      • Lattimer J.M.
      • Haub M.D.
      Effects of dietary fiber and its components on metabolic health.
      ]. Saturated short-chained fatty acids, included mainly in meat and whole-fat dairy products, increase insulin resistance and progression to diabetes. On the contrary, mono-unsaturated long-chained fatty acids, contained in olive oil, are associated with better glycemic control and lower incidence of diabetes [
      • Schwingshackl L.
      • Strasser B.
      • Hoffmann G.
      Effects of monounsaturated fatty acids on glycaemic control in patients with abnormal glucose metabolism: a systematic review and meta-analysis.
      ,
      • Lazarou C.
      • Panagiotakos D.
      • Matalas A.L.
      The role of diet in prevention and management of type 2 diabetes: implications for public health.
      ]. Omega 3-polyunsaturated fatty acids contained in fish oil probably have no effect on glucose metabolism beyond their indirect insulin-sensitizing effect through triglyceride lowering [
      • Abeywardena M.Y.
      • Patten G.S.
      Role of omega3 long-chain polyunsaturated fatty acids in reducing cardio-metabolic risk factors.
      ]. Moderate alcohol drinking (up to 1 drink daily for women and up to 2 drinks daily for men) is reported to have a lowering effect on DM2 incidence and on mean glucose levels in diabetics, possibly by improving insulin sensitivity [
      • Lazarou C.
      • Panagiotakos D.
      • Matalas A.L.
      The role of diet in prevention and management of type 2 diabetes: implications for public health.
      ,
      • Thomas T.
      • Pfeiffer A.F.
      Foods for the prevention of diabetes: how do they work?.
      ]. Although many reports indicate a possible beneficial effect of micronutrient supplements, such as chromium, magnesium, zinc, potassium and antioxidants, the current evidence is not sufficient to support their recommendation in routine clinical practice [
      • Lazarou C.
      • Panagiotakos D.
      • Matalas A.L.
      The role of diet in prevention and management of type 2 diabetes: implications for public health.
      ,
      • Martini L.A.
      • Catania A.S.
      • Ferreira S.R.
      Role of vitamins and minerals in prevention and management of type 2 diabetes mellitus.
      ].

      2.3 Cardiovascular disease

      Cardiovascular disease (CVD) is the leading cause of death worldwide. Ischemic heart disease, stroke and hypertensive heart disease account together for one third of all-cause mortality in high-income countries [

      WHO. Data and statistics. Available from: http://gamapserver.who.int/gho/interactive_charts/mbd/cod_2008/graph.html [accessed 30.08.12].

      ]. CVD is the best disease model where lifestyle modifications can have a profound effect on primary and secondary prevention. Although this has long been appreciated by authorities and much progress has been made with regard to cardiovascular mortality reduction, prevention programs are still inadequate, in particular among women [
      • Ford E.S.
      • Ajani U.A.
      • Croft J.B.
      • et al.
      Explaining the decrease in U.S. deaths from coronary disease, 1980–2000.
      ]. The most important nutritional factor in CVD prevention is the reduction of saturated fat to <7% and of trans fatty acids to <1% of the daily energy intake, since their consumption has consistently shown a strong linear association with coronary heart disease events and stroke, an effect mediated through atherogenic modifications of the lipid profile, insulin resistance, and pro-oxidative mechanisms [
      • Apostolopoulou M.
      • Michalakis K.
      • Miras A.
      • et al.
      Nutrition in the primary and secondary prevention of stroke.
      ,
      • Willett W.C.
      Dietary fats and coronary heart disease.
      ]. Furthermore, the modification and not the reduction of the total fat in the diet appears to be associated with benefit with regard to cardiovascular outcomes [
      • Hooper L.
      • Summerbell C.D.
      • Thompson R.
      • et al.
      Reduced or modified dietary fat for preventing cardiovascular disease.
      ]. In that context, the substitution of saturated fat with omega-3 polyunsaturated fatty acids found in oily fish, as well as of mono-unsaturated fatty acids found in vegetable oils such as olive oil reduces the incidence of acute coronary events, as well as the risk of cardiac death. [
      • Willett W.C.
      Dietary fats and coronary heart disease.
      ,
      • Delgado-Lista J.
      • Perez-Martinez J.
      • Lopez-Miranda J.
      • et al.
      Long chain omega-3 fatty acids and cardiovascular disease: a systematic review.
      ]. Dietary cholesterol may not be as important as once thought [
      • Fernandez M.L.
      Rethinking dietary cholesterol.
      ]; American guidelines still limit the daily intake to 300 mg [
      • Lichtenstein A.H.
      • Appel L.J.
      • Brands M.
      • et al.
      Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee.
      ], while European guidelines do not have an upper limit [
      • Graham I.
      • Atar D.
      • Borch-Johnsen K.
      • et al.
      European guidelines on cardiovascular disease prevention in clinical practice: full text, Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
      ]. Carbohydrates should not be consumed in excess, substituting saturated fat, as they may increase triglyceride levels, decrease high density lipoprotein (HDL)-c and compromise insulin sensitivity. Sources of carbohydrates should be fruits and vegetables, whole grain rice and cereals, nutrients rich in fiber. According to a recent meta-analysis based on prospective observational data, persons consuming >3 servings per day of foods containing fiber had 21% lower risk of CVD and less weight gain during 8–13 years of observation [
      • Ye E.Q.
      • Chacko S.A.
      • Chou E.L.
      • et al.
      Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain.
      ]. Salt intake should be limited, as indicated by its increasing effect on blood pressure. The effect of this intervention on cardiovascular mortality, however, has recently been challenged, as a Cochrane review failed to identify any benefit with regard to cardiovascular morbidity or all-cause deaths [
      • Taylor R.S.
      • Ashton K.E.
      • Moxham T.
      • et al.
      Reduced dietary salt for the prevention of cardiovascular disease.
      ]. Although potentially beneficial, electrolytes, such as potassium and magnesium, as well as antioxidants, should not be routinely recommended for the prevention of CVD [
      • Tinkel J.
      • Hassanain H.
      • Khouri S.J.
      Cardiovascular antioxidant therapy: a review of supplements, pharmacotherapies, and mechanisms.
      ].

      2.4 Cancer

      Beyond smoking, weight management, diet and physical activity are the most important lifestyle parameters modifying cancer risk. Excess body weight, in particular central obesity, has consistently been associated with the risk of various cancers, such as postmenopausal breast cancer [
      • Michels K.B.
      • Mohllajee A.P.
      • Roset-Bahmanyar E.
      • et al.
      Diet and breast cancer: a review of the prospective observational studies.
      ], endometrial cancer [
      • Schmandt R.E.
      • Iglesias D.A.
      • Co N.N.
      • et al.
      Understanding obesity and endometrial cancer risk: opportunities for prevention.
      ], colorectal cancer [
      • Ning Y.
      • Wang L.
      • Giovannucci E.L.
      A quantitative analysis of body mass index and colorectal cancer: findings from 56 observational studies.
      ], renal cancer [
      • Navai N.
      • Wood C.G.
      Environmental and modifiable risk factors in renal cell carcinoma.
      ], as well as adenocarcinoma of the esophagus [
      • Rutegard M.
      • Lagergren P.
      • Nordenstedt H.
      • et al.
      Oesophageal adenocarcinoma: the new epidemic in men?.
      ]. Positive associations with BMI have also been reported for cancers of the liver [
      • Chen Y.
      • Wang X.
      • Wang J.
      • et al.
      Excess body weight and the risk of primary liver cancer: an updated meta-analysis of prospective studies.
      ] and the prostate [
      • Wright M.E.
      • Chang S.C.
      • Schatzkin A.
      • et al.
      Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality.
      ]. Obesity may affect tumorigenesis through various mechanisms, including chronic inflammation, compromised immune function, altered hormone metabolism such as insulin, insulin-like growth factor (IGF) and estrogens, as well as their binding proteins [
      • Kushi L.H.
      • Doyle C.
      • McCullough M.
      • et al.
      American cancer society guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity.
      ]. Healthy dietary patterns aiming to long-term weight control, low in saturated fat and energy dense nutrients and high in fruits, vegetables and beans should actively be recommended as a measure against cancer.
      The consumption of red or processed meat has also consistently been associated with colorectal cancer, a leading cause of cancer death in both sexes. According to a recent meta-analysis, a daily intake of 50 g processed meat or 100 g red meat increases the risk of colorectal cancer by 15–20% [
      • Chan D.S.
      • Lau R.
      • Aune D.
      • et al.
      Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies.
      ]. Many mechanisms may account for this association, among which nitrite/nitrate addition in the processing of meat, nitrosamine formation catalyzed by the iron-containing heme of red meat, mutagens produced by high heat cooking or secretion of secondary bile acids induced by red meat [
      • Vargas A.J.
      • Thompson P.A.
      Diet and nutrient factors in colorectal cancer risk.
      ].
      Accumulating evidence indicates that the consumption of dietary fiber decreases the risk of various cancers including breast [
      • Aune D.
      • Chan D.S.
      • Greenwood D.S.C.
      • et al.
      Dietary fiber and breast cancer risk: a systematic review and meta-analysis of prospective studies.
      ] and colorectal cancer [
      • Aune D.
      • Chan D.S.
      • Lau R.
      • et al.
      Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies.
      ]. Furthermore, large prospective studies have shown that a diet rich in fruit and vegetables may be protective against cancer [
      • George S.M.
      • Park Y.
      • Leitzmann M.F.
      • et al.
      Fruit and vegetable intake and risk of cancer: a prospective cohort study.
      ,
      • Boffetta P.
      • Couto E.
      • Wichmann J.
      • et al.
      Fruit and vegetable intake and overall cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).
      ]. Given their small magnitude, however, these associations should be interpreted with caution, since they may be confounded by lower smoking and obesity rates, or a healthier lifestyle in general of subjects who consume high amounts of fruit and vegetables.
      Alcohol consumption, even in a small degree, is associated with cancer of the breast, mouth, larynx and gastrointestinal tract [
      • Bagnardi V.
      • Rota M.
      • Botteri E.
      • et al.
      Light alcohol drinking and cancer: a meta-analysis.
      ]. Alcohol interacts with smoking to a much higher risk than the risk conferred by the two factors alone [
      • Pelucchi C.
      • Gallus S.
      • Garavello W.
      • et al.
      Alcohol and tobacco use, and cancer risk for upper aerodigestive tract and liver.
      ]. Putative mechanisms explaining the effect of alcohol on cancer are its transformation to the mutagenic acetaldehyde, as well as the prolongation of sex steroid half-life by interference with liver enzymes [
      • Kushi L.H.
      • Doyle C.
      • McCullough M.
      • et al.
      American cancer society guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity.
      ].
      At this time there is no evidence that dietary supplements including, minerals, vitamins and antioxidants have any effect in reducing cancer risk, so their use should not be recommended for cancer prevention [
      • Kushi L.H.
      • Doyle C.
      • McCullough M.
      • et al.
      American cancer society guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity.
      ].

      2.5 Osteoporosis

      Osteoporotic fractures have a life-time risk of 40% for women and 13% for men and account for considerable morbidity and mortality, posing thus a serious socioeconomic burden [
      • Lips P.
      • Bouillon R.
      • van Schoor N.M.
      • et al.
      Reducing fracture risk with calcium and vitamin D.
      ]. Calcium is vital for bone health throughout life. Inadequate dietary intake of calcium is associated with increases in osteoporotic fractures, in particular when vitamin D intake is also low [
      • Warensjo E.
      • Byberg L.
      • Melhus H.
      • et al.
      Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study.
      ]. Calcium supplementation alone can reduce the risk of osteoporotic fractures [
      • Tang B.M.
      • Eslick G.D.
      • Nowson C.
      • et al.
      Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis.
      ], though some investigators have challenged its efficacy [
      • Spangler M.
      • Phillips B.B.
      • Ross M.B.
      • et al.
      Calcium supplementation in postmenopausal women to reduce the risk of osteoporotic fractures.
      ]. High baseline calcium intake, poor adherence to treatment or vitamin D insufficiency may mask the effect of calcium supplementation on fracture risk. Analyses in vitamin D replete or compliant participants indicate a benefit from calcium supplementation with regard to fracture risk [
      • Lips P.
      • Bouillon R.
      • van Schoor N.M.
      • et al.
      Reducing fracture risk with calcium and vitamin D.
      ,
      • Spangler M.
      • Phillips B.B.
      • Ross M.B.
      • et al.
      Calcium supplementation in postmenopausal women to reduce the risk of osteoporotic fractures.
      ]. The current guidelines by most authorities suggest a daily intake of 1000–1200 mg of elemental calcium through either diet or supplementation [
      • Compston J.
      • Cooper A.
      • Cooper C.
      • et al.
      Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK.
      ]. However caution has been expressed in using calcium supplements in women whose diet is replete. Thus the Women's Health Initiative (WHI) study found an increased risk of kidney stones [
      • Jackson R.D.
      • LaCroix A.Z.
      • Gass M.
      • et al.
      Women's health initiative investigators, calcium plus vitamin D supplementation and the risk of fractures.
      ]. Also calcium supplement use is associated with an increased risk of myocardial infarction and, possibly, stroke [
      • Reid I.R.
      • Bolland M.J.
      • Sambrook P.N.
      • et al.
      Calcium supplementation: balancing the cardiovascular risks.
      ]. This risk is not mitigated by co-administration of vitamin D. It is probably safer to achieve adequate through dietary modification rather than using supplements. Beyond dairy products, calcium-rich nutrients include small fish eaten with the skeleton, figs, tahini paste and sesame seeds [

      International Osteoporosis Foundation. Calcium-rich foods. Available from: http://www.iofbonehealth.org/calcium-rich-foods [accessed 16.09.12].

      ].
      Vitamin D is essential for optimal calcium absorption. Vitamin D deficiency increases bone turnover through secondary hyperparathyroidism and leads to bone loss [
      • Perez-Lopez F.R.
      • Brincat M.
      • Erel C.T.
      • et al.
      EMAS position statement: vitamin D and postmenopausal health.
      ]. Beyond its effect on bone metabolism, vitamin D may act beneficially on osteoporotic fractures by decreasing the risk of falls [
      • Perez-Lopez F.R.
      • Brincat M.
      • Erel C.T.
      • et al.
      EMAS position statement: vitamin D and postmenopausal health.
      ]. Dietary sources of vitamin D are rather limited and include oily fish and fortified dairy products [

      International Osteoporosis Foundation. Vitamin D rich foods. Available from: http://www.iofbonehealth.org/vitamin-d [accessed 16.09.12].

      ]. The prevalence of vitamin D insufficiency may be high especially in the elderly, the obese, the dark skinned or the people with minimal exposure to sunlight. Given the safety of vitamin D supplementation, its efficacy along with calcium on fracture prevention [
      • Tang B.M.
      • Eslick G.D.
      • Nowson C.
      • et al.
      Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis.
      ] and its possible beneficial effect on neuromuscular and cardiovascular system [
      • Perez-Lopez F.R.
      • Chedraui P.
      • Fernandez-Alonso A.M.
      Vitamin D and aging: beyond calcium and bone metabolism.
      ], a daily allowance of 800 IU is recommended for optimal bone health [
      • Compston J.
      • Cooper A.
      • Cooper C.
      • et al.
      Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK.
      ]. Individuals with documented insufficiency may need higher doses to restore optimal serum vitamin D levels [
      • Perez-Lopez F.R.
      • Brincat M.
      • Erel C.T.
      • et al.
      EMAS position statement: vitamin D and postmenopausal health.
      ]. Cholecalciferol (D3) should be preferred over active metabolites of vitamin D, as the latter do not increase serum 25OH vitamin D, which is important for non-renal tissue production of active vitamin D, and they are associated with higher rates of hypercalcemia [
      • Bjelakovic G.
      • Gluud L.L.
      • Nikolova D.
      • et al.
      Vitamin D supplementation for prevention of mortality in adults.
      ,
      • Dawson-Hughes B.
      • Mithal A.
      • Bonjour J.P.
      • et al.
      IOF position statement: vitamin D recommendations for older adults.
      ].
      Protein intake, in particular of animal origin, has been positively associated with higher bone mineral density (BMD) as well as with lower rates of osteoporotic fractures and post-fracture complications [
      • Bonjour J.P.
      Protein intake and bone health.
      ,
      • Body J.J.
      • Bergmann P.
      • Boonen S.
      • et al.
      Non-pharmacological management of osteoporosis: a consensus of the Belgian bone club.
      ]. This association may be mediated through higher calcium absorption, higher IGF-1 production and increased muscle mass induced by a high-protein diet [
      • Body J.J.
      • Bergmann P.
      • Boonen S.
      • et al.
      Non-pharmacological management of osteoporosis: a consensus of the Belgian bone club.
      ,
      • Cao J.J.
      • Nielsen F.H.
      Acid diet (high-meat protein) effects on calcium metabolism and bone health.
      ]. Other studies have failed to corroborate this association, possibly due to low calcium intake in the population studied or to longevity bias, since persons with high protein intake may live longer and sustain more fractures [
      • Body J.J.
      • Bergmann P.
      • Boonen S.
      • et al.
      Non-pharmacological management of osteoporosis: a consensus of the Belgian bone club.
      ]. In view of this evidence, the daily recommended allowance of 0.8 g protein/Kg body weight may not meet the needs for lean body mass preservation and healthy bone turnover, especially in the elderly [
      • Cao J.J.
      • Nielsen F.H.
      Acid diet (high-meat protein) effects on calcium metabolism and bone health.
      ,
      • Elango R.
      • Humayun M.A.
      • Ball R.O.
      • et al.
      Evidence that protein requirements have been significantly underestimated.
      ].
      High alcohol consumption is associated with decreased BMD and higher rates of osteoporotic fractures [
      • Body J.J.
      • Bergmann P.
      • Boonen S.
      • et al.
      Non-pharmacological management of osteoporosis: a consensus of the Belgian bone club.
      ]. Alcohol acts directly by inhibiting bone formation and indirectly by increasing the risk of falls and of malnutrition [
      • Maurel D.B.
      • Boisseau N.
      • Benhamou C.L.
      • et al.
      Alcohol and bone: review of dose effects and mechanisms.
      ]. Moderate drinking, however, has not been shown to affect negatively bone health [
      • Body J.J.
      • Bergmann P.
      • Boonen S.
      • et al.
      Non-pharmacological management of osteoporosis: a consensus of the Belgian bone club.
      ,
      • Maurel D.B.
      • Boisseau N.
      • Benhamou C.L.
      • et al.
      Alcohol and bone: review of dose effects and mechanisms.
      ].

      2.6 Osteoarthritis

      Osteoarthritis (OA) is a disabling, degenerative disease, which is more common in women than in men after the fifth decade [
      • Tanamas S.K.
      • Wijethilake P.
      • Wluka A.E.
      • et al.
      Sex hormones and structural changes in osteoarthritis: a systematic review.
      ]. Known risk factors for OA include age, gender and obesity. Weight reduction can reduce pain and improve mobility [
      • Runhaar J.
      • Koes B.W.
      • Clockaerts S.
      • et al.
      A systematic review on changed biomechanics of lower extremities in obese individuals: a possible role in development of osteoarthritis.
      ,
      • Vincent H.K.
      • Heywood K.
      • Connelly J.
      • et al.
      Obesity and weight loss in the treatment and prevention of osteoarthritis.
      ]. With regard to specific dietary components, some studies suggest that vitamin C and vitamin D may reduce disease progression, sympton severity and cartilage loss [
      • Bergink A.P.
      • Uitterlinden A.G.
      • Van Leeuwen J.P.
      • et al.
      Vitamin D status, bone mineral density, and the development of radiographic osteoarthritis of the knee: The Rotterdam Study.
      ,
      • Peregoy J.
      • Wilder F.V.
      The effects of vitamin C supplementation on incident and progressive knee osteoarthritis: a longitudinal study.
      ]. Polyphenols in olive oil and polyinsaturated omega-3 fatty acids may reduce inflammation [
      • Baker K.R.
      • Matthan N.R.
      • Lichtenstein A.H.
      • et al.
      Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis in the knee: the MOST study.
      ].
      Glucosamine and chondroitin supplements are popular dietary supplements used for OA. However the evidence supporting efficacy is poor with the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) study investigators showing that the combination of glucosamine and chondroitin did little to alleviate the progression of disease or pain in people with mild to moderate knee OA and further studies are warranted [
      • Clegg D.
      • Reda D.J.
      • Harris C.L.
      • et al.
      Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis.
      ,
      • Sherman A.L.
      • Ojeda-Correal G.
      • Mena J.
      Use of glucosamine and chondroitin in persons with osteoarthritis.
      ].

      2.7 Cognitive function

      Much attention has been focused today on the possible effects of diet on the development and the progression of dementia. The most convincing evidence concerns the protective effect of vitamin E, folate, vitamin B12 and omega-3 fatty acids. Most studies examining the effect of dietary vitamin E intake on cognitive performance have found positive results, especially in populations with low dietary intake [
      • Morris M.C.
      Nutritional determinants of cognitive aging and dementia.
      ]. Beyond its antioxidant function, vitamin E may be involved in signal transduction, gene expression and redox sensing [
      • Joshi Y.B.
      • Pratico D.
      Vitamin E in aging, dementia, and Alzheimer's disease.
      ]. On the contrary, clinical studies investigating the use of vitamin E supplements have not documented any benefit [
      • Isaac M.G.
      • Quinn R.
      • Tabet N.
      Vitamin E for Alzheimer's disease and mild cognitive impairment.
      ]. Health-consciousness of trial participators with higher baseline vitamin E concentration or differences in dietary vitamin E activity, as compared to the supplemented may account for the observed lack of efficacy of supplements on cognitive function [
      • Morris M.C.
      Nutritional determinants of cognitive aging and dementia.
      ].
      Folate and vitamin B12 are co-factors involved in the metabolism of homocysteine, an important modulator of the neurodegenerative process [
      • Morris M.C.
      Nutritional determinants of cognitive aging and dementia.
      ]. Low levels of these two vitamins, as well as increased circulating homocysteine have been associated with lower cognitive performance and higher risk of developing dementia [
      • Nachum-Biala Y.
      • Troen A.M.
      B-vitamins for neuroprotection: narrowing the evidence gap.
      ,
      • Camfield D.A.
      • Owen L.
      • Scholey A.B.
      • et al.
      Dairy constituents and neurocognitive health in ageing.
      ]. As in the case of vitamin E, however, intervention studies have not demonstrated an efficacy of follate and vitamin B12 supplementation in preventing cognitive decline [
      • Nachum-Biala Y.
      • Troen A.M.
      B-vitamins for neuroprotection: narrowing the evidence gap.
      ,
      • Aisen P.S.
      • Schneider L.S.
      • Sano M.
      • et al.
      High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial.
      ].
      A diet rich in saturated fat is associated with faster cognitive decline and increased risk of dementia [
      • Morris M.C.
      Nutritional determinants of cognitive aging and dementia.
      ,
      • Perez L.
      • Heim L.
      • Sherzai A.
      • et al.
      Nutrition and vascular dementia.
      ]. On the contrary, fish consumption, rich in omega-3 polyunsaturated fatty acids has been shown as protective against cognitive decline [
      • Perez L.
      • Heim L.
      • Sherzai A.
      • et al.
      Nutrition and vascular dementia.
      ]. These effects may also be mediated through modifications in cardiovascular risk, in particular concerning vascular dementia [
      • Morris M.C.
      Nutritional determinants of cognitive aging and dementia.
      ]. Clinical trials and prospective intervention studies with omega-3 fatty acid supplementation have not shown so far an effect either on cognitive performance of healthy older people, or on the incidence and progression of dementia [
      • Dangour A.D.
      • Andreeva V.A.
      • Sydenham E.
      • et al.
      Omega 3 fatty acids and cognitive health in older people.
      ,
      • Sydenham E.
      • Dangour A.D.
      • Lim W.S.
      Omega 3 fatty acid for the prevention of cognitive decline and dementia.
      ].

      3. Healthy eating patterns

      Early observations on differences in longevity and in the incidence of the major non-communicable disease by geographic variation led to the study of specific dietary patterns in health promotion [
      • Menotti A.
      • Keys A.
      • Aravanis C.
      • et al.
      Seven countries study, first 20-year mortality data in 12 cohorts of six countries.
      ]. The Mediterranean diet (Mediet) is the diet best studied and increasingly strong evidence supports its preventive effect on many midlife medical conditions [
      • Perez-Lopez F.R.
      • Chedraui P.
      • Haya J.
      • et al.
      Effects of the Mediterranean diet on longevity and age-related morbid conditions.
      ]. Mediet is more a lifestyle philosophy than a mere combination of nutrients, consisting of frequent communal meals, daily moderate exercise and moderate red wine consumption along with meals [
      • Bonaccio M.
      • Iacoviello L.
      • de Gaetano G.
      • et al.
      The Mediterranean diet: the reasons for a success.
      ]. Cooked or raw seasonal vegetables, beans and legumes, as well as moderate amounts of cheese, yoghurt and fish are the basis of the Meddiet. The avid consumption of olive oil characterizes Mediterranean eating habits. Meat is consumed rarely and saturated fat is usually less than 7% of the total daily calories [
      • Perez-Lopez F.R.
      • Chedraui P.
      • Haya J.
      • et al.
      Effects of the Mediterranean diet on longevity and age-related morbid conditions.
      ]. Adherence to Mediet among Mediterranean populations has consistently shown a lower total, CVD and cancer mortality and possibly lower incidence of neurodegenerative diseases [
      • Tyrovolas S.
      • Panagiotakos D.B.
      The role of Mediterranean type of diet on the development of cancer and cardiovascular disease, in the elderly: a systematic review.
      ,
      • Solfrizzi V.
      • Frisardi V.
      • Seripa D.
      • et al.
      Mediterranean diet in predementia and dementia syndromes.
      ,
      • Dilis V.
      • Katsoulis M.
      • Lagiou P.
      • et al.
      Mediterranean diet and CHD: the Greek European Prospective Investigation into Cancer and Nutrition cohort.
      ,
      • Couto E.
      • Boffetta P.
      • Lagiou P.
      • et al.
      Mediterranean dietary pattern and cancer risk in the EPIC cohort.
      ].
      Vegetarian diets have gained popularity as a healthy way of living. Vegetarians have been shown to have lower all-cause mortality and lower incidence of coronary heart disease, diabetes and hypertension, an effect partially mediated by the lower BMI of vegetarians [
      • Fraser G.E.
      Vegetarian diets: what do we know of their effects on common chronic diseases?.
      ]. Data on cancer incidence and mortality are still inconclusive [
      • Fraser G.E.
      Vegetarian diets: what do we know of their effects on common chronic diseases?.
      ,
      • Key T.J.
      • Fraser G.E.
      • Thorogood M.
      • et al.
      Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies.
      ,
      • Key T.J.
      • Appleby P.N.
      • Spencer E.A.
      • et al.
      Cancer incidence in vegetarians: results from the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford).
      ,
      • Craig W.J.
      Nutrition concerns and health effects of vegetarian diets.
      ]. The difficulty in establishing associations lies mainly in the fact that the term “vegetarian” includes many diet patterns, namely lacto-ovo-vegetarians who consume animal products, pesco-vegetarians who consume fish and vegans who consume no meat, poultry, fish or animal products. The latter category is subject to deficiencies of vitamin D, calcium, vitamin B12, iron and zinc [
      • Fraser G.E.
      Vegetarian diets: what do we know of their effects on common chronic diseases?.
      ,
      • Craig W.J.
      Nutrition concerns and health effects of vegetarian diets.
      ].

      4. Conclusion

      A healthy diet is essential for the prevention of all major chronic non-communicable diseases in midlife and beyond, both directly, through the effect of individual macro- and micronutrients and indirectly, through the control of body weight. Adequate protein intake should be ensured mainly from fish, poultry, low-fat dairy products or legumes. Carbohydrates should be derived from whole grain cereals, fruits and vegetables, nutrients rich in fiber, while the consumption of sugared or refined products should be discouraged. Saturated fat contained in red meat and whole-fat dairy products should be limited to <7% of the total calorie intake. Fat energy should be derived from plant oils, in particular olive oil which is rich in monounsaturated fatty acids. Moderate alcohol consumption may confer some benefit with regard to cardiovascular disease prevention. People, however, who do not consume alcohol should not be encouraged to do so on the sole basis of these findings. Beyond calcium and vitamin D supplementation for the prevention of fractures, currently there is no adequate evidence to support the use of supplements for the prevention of midlife chronic diseases.

      5. Summary recommendations

      • Diet may modify the epidemiology of the major midlife diseases, namely diabetes, cardiovascular disease, cancer, osteoporosis and dementia.
      • Sarcopenic obesity in the elderly may be masked by a “normal” BMI and should be managed with adequate protein intake and tailored physical exercise.
      • Diabetes mellitus type 2 is best prevented or managed by restricting the total amount of carbohydrate in the diet and by deriving carbohydrate energy from whole-grain cereals, fruits and vegetables.
      • The substitution of saturated and trans-fatty acids by mono-unsaturated and omega-3 fatty acids is the most important dietary intervention for the prevention of cardiovascular disease.
      • Obesity is a risk factor for a variety of cancers. The consumption of red or processed meat is associated with an increase of colorectal cancer.
      • Adequate protein, calcium and vitamin D intake should be ensured for the prevention of osteoporotic fractures. Surveillance is needed for possible vitamin D deficiency in high risk populations.
      • A diet rich in vitamin E, folate, B12 and omega-3 fatty acids may be protective against cognitive decline.
      • Beyond calcium and vitamin D, routine supplementation of vitamins, antioxidants or micronutrients is not warranted at present for the prevention of chronic diseases.
      • The Mediterranean diet is reported to protect against cardiovascular disease, cancer and possibly cognitive decline.
      • Vegetarian diets are associated with lower incidence of diabetes, hypertension and cardiovascular disease.

      Contributors

      None.

      Competing interest

      None declared.

      Funding

      None.

      Provenance and peer review

      EMAS position statement.

      Acknowledgements

      IL prepared the initial draft which was circulated to all EMAS board members for comment and approval, production was coordinated by MR and IL.

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