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Dietary supplements for healthy aging
Selections from recent literature
Human aging is a physiological process that involves changes in body structure and function. Several dietary supplements offer the possibility of preventing or delaying age-related decline. Here we summarize recent reports dealing with the prevention of some of the main signs of aging: cognitive impairment, sarcopenia, skin appearance, dry eye disease and immunosenescence.
Vitamin C and E may reduce the risk of cognitive decline 
Although brain functioning undergoes physiological age-related decay, cognitive decline is generally considered a stage of transition between normal aging and Alzheimer’s disease (AD).
Oxidative stress is recognized as one of the factors contributing to this process. There are few studies of the association between the use of antioxidant vitamin supplements and the risk of cognitive impairment. To this purpose, researchers from the Centre of Excellence for the Aging in Quebec and the Centre for Health Social Services of Chicoutimi evaluated whether the use of vitamin E and C supplements is associated with reduced risks of cognitive impairment not dementia (CIND), AD or all-cause dementia, in a representative sample of older persons aged 65 and above. Data collected from 1991 to 2002 for the Canadian Study of Health and Aging, a cohort study of dementia including three evaluation waves at 5-yearly intervals, were used. Exposure to vitamins E and C was self-reported at baseline in a risk factor questionnaire and/or at a clinical examination.
The Authors analyzed data from 5,269 individuals, and found that the use of vitamin E and/or C supplements was significantly associated with 40% and 42% decreases in the risk of all -cause dementia and AD, respectively, compared with no vitamin supplements.
When vitamins were analyzed separately, vitamin C was associated with 43% and 31% decreases in the risk of AD and CIND , and vitamin E with 46% and 32% reductions in the risk of AD and CIND, respectively, compared to no use.
The researchers concluded that, although this analysis suggests that the use of vitamin E and C supplements is associated with a reduced risk of cognitive decline, further investigations are needed to determine the value of supplementation with these vitamins as a primary prevention strategy.
Effect of supplementation and physical activity in elderly subjects with sarcopenia 
Older adults experience progressive, generalized loss of skeletal muscle and a decrease in physical function, with an increasing risk of disability and poor quality of life. Intervention saimed to attenuate the adverse effects of age-related loss of skeletal muscle and function include physical activity and nutritional therapy. A registered randomized, double-blind, placebo-controlled supplementation trial (NCT02402608) was carried out in 130 elderly subjects with sarcopenia (53 men and 77 women; mean age 80.3 years) admitted to the geriatric physical medicine and rehabilitation division at Santa Margherita Hospital, Azienda Human Service of Pavia(I), to test the hypothesis that nutritional supplementation with whey protein (22g), essential aminoacids (10.9g, including 4 gleucine) and vitamin D (2.5µg,100IU) concurrently with a regular, controlled physical activity program, would increase fat- free mass, strength, physical function and quality of life, and reduce the risk of malnutrition in elderly individuals with sarcopenia.
Subjects were randomly assigned to receive the dietary supplement or placebo (an isocaloric amount of maltodextrin with the same flavour and appearance a s the intervention product) orally once a day at 12.00 noon with a meal for 12 weeks. No side effects were reported during the study.
The results indicated that, compared with physical activity and placebo, supplementation plus physical activity (i) significantly increased fat-free mass (FFM;+1.7kg gain), relative skeletal muscle mass, android distribution of fat, handgrip strength, standardized summary scores for physical components, activities of daily living, and Mini Nutritional Assessment scores, (ii) attenuated the inflammatory state, as shown by a significant drop in C-reactive protein (CRP) concentrations, and (iii) enhanced the anabolic growth hormone (GH)IGF-I hormone axis, with significant increases in IGF-I concentrations and a reduction in the indexes of mal nutrition.
In conclusion, this study suggests that whey protein, essential aminoacids and vitamin D supplementation together with gentle physical activity can bring about changes in catabolic mediators, lowering inflammatory markers such as CRP and improving anabolic markers such as IGF-I. This results in a significant increase in FFM and muscles trength, proving effective in the treatment of sarcopenia, with improvements in physical function and quality of life.
Marine collagen peptides and plant-derived antioxidants supplement with skin anti-ageing properties 
The use of nutraceuticals targeting the skin is steadily growing: dietary vitamins, plant-derived polyphenols, fatty acids, proteins, essential aminoacids and trace elements have demonstrated beneficial effects on skin health and appearance.
Collagen peptides, obtained by enzymatic digestion of fish, bovine, and porcine skin, are utilized as functional foods or dietary supplements, mainly for skin and bone repair and in patients with osteoarthritis. Research into and the development of nutraceuticals based on marine collagen peptides (MCPs) has increased because of their structural similarity to human collagen, safety profile, stability, biocompatibility, high bioavailability due to their ability to pass through the gastrointestinal barrier, and potent bioactivities. However, the increased risk of oxidative stress associated with collagen synthesis and ROS production by MCP-stimulated phagocytes is a major concern. A single-blind case–controlled clinical study was carried out to examine the effect of a combination of MCP and skin-targeting plant-derived antioxidants on skin physiology and dermal collagen deposition in a group of healthy middle-aged subjects with clinical signs of skin ageing.
A food supplement containing MCPs derived from the skin of deep-sea fish (570mg), grape-skin extract (10mg), coenzyme Q10 derived from plants (10mg), luteolin (10mg) and selenium (0.05mg) derived from plants was formulated in soft gelatine capsules. The study enrolled 41 adult healthy Caucasian volunteers of both sexes (5 male sand 36 females), aged 37–72 years (mean age 50.6±10.4 years). The trial lasted from May to December 2014, and consisted of a 2-month pretreatment period followed by 2 months of treatment with the test nutraceutical (two capsules a day, at break fast and dinner time). The facial skin parameters of volunteers were analysed three times: at the first visit (enrolment), at the second visit at the end of the 2-month pretreatment period, and at the third visit immediately after the treatment period.
The results provided convincing clinical data on the efficacy of the MCP and plant antioxidant formulation in improving dermal collagen deposition and structure, as well as skin elasticity. These effects were consistent with enhanced plasma levels of hydroxyproline, a systemic metabolic marker of collagen synthesis. The anti-ageing effects of the supplementation were also demonstrated by greatly increased sebum production. Redox parameters, GSH/coenzyme Q10 content, and GPx/GST activities were unchanged, while NO and MDA were moderately increased within the normal range of values.
The Authors concluded that “the addition of dietary plant-derived antioxidants with known skin tropism and health effects towards human skin did not impair definite induction of collagen synthesis and its deposition as compact organised fibres in the dermal layer by marine fish skin-derived collagen peptides. Additional beneficial effects of antioxidants were observed systemically, as the normal balance of systemic endogenous antioxidant defence was maintained, and protection of energy storage occurred”. However, more basic research and further clinical studies are needed to examine the hypothesis that a combination of MCP and skin-targeting antioxidants could improve skin properties without risking oxidative damage, and to evaluate the underlying mechanisms.
Omega-3 fatty acids, vitamins, minerals and antioxidant supplementation may improve dry eye symptoms 
Dry eye is a multifactorial disorder affecting tears and the ocular surface, and is commonly seen in women and the elderly. Researchers of the Dry Eye Clinical Study Group (Barcelona,Spain) assessed the benefits and tolerability of a dietary supplement based on omega-3 fatty acids, vitamins, minerals and antioxidant store lieve dry eye symptoms in a 12-week prospective study. This was an open-label, prospective, non-comparative, intervention and multicentre study carried out in ophthalmological clinics through out Spain under conditions of daily practice.
A total of 1419 patients of both sexes (74.3% women), with a mean age 58.9 years and on current treatment with artificial tears due to dry eye disease, were instructed to take the supplement under study (three capsules once daily with a main meal excluding breakfast). Each capsule contained: TG-DHA 70% 350 mg, EPA 8.5% 42.5 mg, DPA 6% 30 mg, vitamin A (retinol) 133.3 µg, vitamin C (ascorbic acid) 26.7 mg, vitamin E (d-α-tocopherol) 4 mg, zinc 1.6 mg, copper 0.16 mg, magnesium 0.33 mg, selenium 9.17 µg, tyrosine 10.8 mg, cysteine 5.83 mg and glutathione 2 mg. TG-DHA is a concentrated DHA triglyceride with high antioxidant activity, patented to prevent cellular oxidative damage.
After 12 weeks of supplementation, statistically significant improvements in all study variables (p<0.001) were seen. The mean (SD) total dry eye symptom score decreased from 9.67±6.38 to 4.22±4.71 (p<0.001). The mean number of daily instillations of artificial tears also decreased signifi¬cantly from 3.77±2.08 to 3.45±1.72 (p<0.01). Significant differences in the improvement in dry eye symptoms were also seen in compliant versus non-compliant patients as well as in those with moderate/severe versus none/mild conjunctival hyperemia.
The nutraceutical formulation was tolerated very well, with some 80% of patients experiencing no adverse events. None of the participants discontinued the nutraceutical supplement because of serious adverse events.
The Authors concluded that “despite the limitation of the open-label design, the lack of a control group, and the treatment period limited to 12 weeks, the large number of participants and the fact that data were obtained in daily clinical practice add strength to the findings”.
Effect of probiotics on immune function in healthy elderly subjects 
Elderly people are the fastest growing segment of the population globally. Typically, the elderly have weaker immune responses to vaccination and an elevated risk of infection, particular autoimmune diseases and cancer. Some of these health risks are a consequence of weakening immune function associated with the aging process, i.e., immunosenescence. The gut microbiota plays a significant role in immunosenescence and is influenced by the physiological aging process, lifestyle and diet. Research shows that the gut microbiota of the elderly has specific features compared to the microbiota of younger adults, such as lower levels of bifidobacteria and higher levels of Bacteroidetes spp. These changes in microbiota composition may be indicative of dysbiosis and poorer health. Therefore, targeted dietary interventions which restore microbiota composition could potentially help maintain overall health and improve the quality of the life of the elderly. A new systematic review and meta-analysis, published in February 2017, shows that daily consumption of Bifidobacterium animalis ssp. lactis HN019™ enhances cellular immune activity in healthy elderly adults. Four clinical trials were included in the analysis. A systematic review and meta-analysis of randomized controlled trials that reported polymorphonuclear (PMN) phagocytosis activity or natural killer (NK) cell tumoricidal activity following B. lactis HN019™ consumption in the elderly were conducted. A random effects meta-analysis was performed using standardized mean difference statistics between probiotic and control groups for each outcome. One study was a randomized trial with a parallel control group, while three studies used a 3-week run-in period as the control. Subjects in each study were healthy elderly adults with a median age between 60 and 70 years. The interventions evaluated were daily consumption of low-fat milk, with or without B. lactis HN019™. The daily doses of B. lactis HN019™ ranged from 5×109 to 3×1011 colony forming units (CFUs) and treatment duration ranged from 3 to 6 weeks.
Data showed that B. lactis HN019™ supplementation was highly efficacious in increasing PMN phagocytic capacity with a standardized mean difference (SMD) of 0.74 (95% CI 0.38 to 1.11, p<0.001) and moderately efficacious in increasing NK cell tumoricidal activity with an SMD of 0.43 (95% CI 0.08 to 0.78, p=0.02).
“This is the first systematic review and meta-analysis of the probiotic strain Bifidobacterium animalis ssp. lactis HN019™ in relation to immune function in [the] elderly – a highly relevant target group since elderly people have increased susceptibility to infections and cancer that are associated with decline in cellular immune function”, said Liisa Lehtoranta, Research Manager at DuPont Nutrition & Health and co-author of the article. In conclusion, although the main limitations of this research were the small number of included studies, the short follow-up period, and assessment of a single probiotic strain, the study suggests that daily consumption of B. lactis HN019™ enhances cellular immune activity in healthy elderly adults.
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2. Rondanelli M, Klersy C, Terracol G, et al (2016) Whey protein, aminoacids, and vitamin D supplementation with physical activity increases fat-free mass and strength, functionality, and quality of life and decreases inflammation in sarcopenic elderly. Am J Clin Nutr 103(3):830–840
3. De Luca C, Mikhal’chik EV, Suprun MV, et al (2016) Skin antiageing and systemic redox effects of supplementation with marine collagen peptides and plant-derived antioxidants: a single-blind case-control clinical study. Oxid Med Cell Longev 2016:4389410
4. Gatell-Tortajada J (2016) Oral supplementation with a nutraceutical formulation containing omega-3 fatty acids, vitamins, minerals, and antioxidants in a large series of patients with dry eye symptoms: results of a prospective study. Clin Interv Aging 11:571–578
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