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Plant-Based Diets Are Associated With a Lower Risk of Incident Cardiovascular Disease, Cardiovascular Disease Mortality, and All-Cause Mortality in a General Population of Middle-Aged Adults.
Kim, H, Caulfield, LE, Garcia-Larsen, V, Steffen, LM, Coresh, J, Rebholz, CM
Journal of the American Heart Association. 2019;8(16):e012865
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Plant based diets have been associated with better health outcomes, however mixed results have been shown on their relationship with death by any cause and death due to heart disease. This cohort study of 15792 middle aged people aimed to determine if plant-based diets are associated with a lower risk of heart disease, death due to heart disease or death due to any cause and whether this was on a sliding scale depending on adherence to a healthful plant-based diet. The results showed that individuals following a plant-based diet had a 16% lower risk of heart disease, 32% lower risk of death due to heart disease and a 25% lower risk of death by any cause and individuals who followed a healthier plant-based diet were at an even lower risk of heart disease, death due to heart disease and death due to any cause. Interestingly when margarine was included in an individual’s diet, the decreased risk of heart disease was attenuated. It was concluded that higher adherence to a healthy plant-based diet was associated with a lower risk of heart disease, death due to heart disease and death by any cause. This study could be used by healthcare practitioners to recommend a plant-based diet to those at an increased risk of heart disease.
Abstract
Background Previous studies have documented the cardiometabolic health benefits of plant-based diets; however, these studies were conducted in selected study populations that had narrow generalizability. Methods and Results We used data from a community-based cohort of middle-aged adults (n=12 168) in the ARIC (Atherosclerosis Risk in Communities) study who were followed up from 1987 through 2016. Participants' diet was classified using 4 diet indexes. In the overall plant-based diet index and provegetarian diet index, higher intakes of all or selected plant foods received higher scores; in the healthy plant-based diet index, higher intakes of only the healthy plant foods received higher scores; in the less healthy plant-based diet index, higher intakes of only the less healthy plant foods received higher scores. In all indexes, higher intakes of animal foods received lower scores. Results from Cox proportional hazards models showed that participants in the highest versus lowest quintile for adherence to overall plant-based diet index or provegetarian diet had a 16%, 31% to 32%, and 18% to 25% lower risk of cardiovascular disease, cardiovascular disease mortality, and all-cause mortality, respectively, after adjusting for important confounders (all P<0.05 for trend). Higher adherence to a healthy plant-based diet index was associated with a 19% and 11% lower risk of cardiovascular disease mortality and all-cause mortality, respectively, but not incident cardiovascular disease (P<0.05 for trend). No associations were observed between the less healthy plant-based diet index and the outcomes. Conclusions Diets higher in plant foods and lower in animal foods were associated with a lower risk of cardiovascular morbidity and mortality in a general population.
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Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target.
Sorgdrager, FJH, Naudé, PJW, Kema, IP, Nollen, EA, Deyn, PP
Frontiers in immunology. 2019;10:2565
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Inflammation is a normal physiological process activated by the immune system in response to injury or infection. As we age, the immune system changes and the balance between pro- and anti-inflammatory agents can shift. This causes a chronic inflammatory state referred to as inflammaging. The rate of inflammaging is strongly associated with age-related disability, disease and mortality. The way in which the essential amino acid tryptophan (Trp) is broken down affects inflammation. If it is converted to kynurenine (Kyn) and its metabolites, inflammation is modulated. Studies have shown that the Kyn/Trp ratio, measured in blood, is strongly associated with ageing in humans. It could therefore be a useful marker to predict the onset of age-related diseases. This review discusses the metabolism of Trp and the links to inflammation. The authors hypothesize how intervening in these pathways could impact health- and lifespan. Future studies are needed to confirm the value of Trp metabolism as a biomarker for (un)healthy ageing and as drug target for inflammaging-related disease.
Abstract
Inflammation aims to restore tissue homeostasis after injury or infection. Age-related decline of tissue homeostasis causes a physiological low-grade chronic inflammatory phenotype known as inflammaging that is involved in many age-related diseases. Activation of tryptophan (Trp) metabolism along the kynurenine (Kyn) pathway prevents hyperinflammation and induces long-term immune tolerance. Systemic Trp and Kyn levels change upon aging and in age-related diseases. Moreover, modulation of Trp metabolism can either aggravate or prevent inflammaging-related diseases. In this review, we discuss how age-related Kyn/Trp activation is necessary to control inflammaging and alters the functioning of other metabolic faiths of Trp including Kyn metabolites, microbiota-derived indoles and nicotinamide adenine dinucleotide (NAD+). We explore the potential of the Kyn/Trp ratio as a biomarker of inflammaging and discuss how intervening in Trp metabolism might extend health- and lifespan.
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Examining Weight Bias among Practicing Canadian Family Physicians.
Alberga, AS, Nutter, S, MacInnis, C, Ellard, JH, Russell-Mayhew, S
Obesity facts. 2019;12(6):632-638
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Weight bias represents negative attitudes and beliefs about individuals because of their weight. The aim of this study was to examine: a. weight bias in a national sample of family physicians in Canada, b. the relationships between weight bias, attitudes about treating patients with obesity, and how people with obesity are perceived as a burden to the public healthcare system. A probability sample of 400 currently practicing family physicians completed the survey by phone or online. Results show that most respondents were white (63.3%) men (61.3%) aged 45 years or older. The average total score of explicit weight bias was 2.95 (1.17) evaluated on a 7-point Likert scale. Furthermore, although weight bias was not present in the majority of the sample, it was present among some physicians. Authors conclude that future work is needed to investigate weight bias reduction techniques targeted at physicians.
Abstract
OBJECTIVES The aim of this study was to examine the attitudes of practicing Canadian family physicians about individuals with obesity, their healthcare treatment, and perceptions of obesity treatment in the public healthcare system. METHOD A national sample of Canadian practicing family physicians (n = 400) completed the survey. Participants completed measures of explicit weight bias, attitudes towards treating patients with obesity, and perceptions that people with obesity increase demand on the public healthcare system. RESULTS Responses consistent with weight bias were not observed overall but were demonstrated in a sizeable minority of respondents. Many physicians also reported feeling frustrated with patients with obesity and agreed that people with obesity increase demand on the public healthcare system. Male physicians had more negative attitudes than females. More negative attitudes towards treating patients with obesity were associated with greater perceptions of them as a public health demand. CONCLUSION Results suggest that negative attitudes towards patients with obesity exist among some family physicians in Canada. It remains to be determined if physicians develop weight bias partly because they blame individuals for their obesity and its increased demand on the Canadian public healthcare system. More research is needed to better understand causes and consequences of weight bias among health professionals and make efforts towards its reduction in healthcare.
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Oral glutamine supplements reduce concurrent chemoradiotherapy-induced esophagitis in patients with advanced non-small cell lung cancer.
Chang, SC, Lai, YC, Hung, JC, Chang, CY
Medicine. 2019;98(8):e14463
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Non-small cell lung cancer (NSCLC) is commonly treated with concurrent chemo- and radiation therapy (CCRT). This treatment often causes acute radiation-induced oesophagitis (ARIE) which can lead to significant weight loss and unplanned treatment delays. This prospective randomised study assessed whether glutamine supplementation may prevent ARIE in advanced NSCLC patients. Patients were randomised to receive either standard treatment (CCRT) with prophylactic oral glutamine, 30 grams/day, or standard treatment alone. The patients in the glutamine group received glutamine for 1 year. Compared with the control group, the oral glutamine supplement group had significantly less severe ARIE, and in those patients who developed ARIE, onset was significantly delayed in the glutamine group. The incidence of weight loss was also significantly reduced in the glutamine group. There was no statistically significant difference in cancer progression-free survival between the two groups (median follow-up period 26.4 months). Glutamine supplementation was well tolerated by all patients. The authors conclude that oral glutamine supplementation has a benefit in delaying onset of and decreasing the severity of ARIE in advanced lung cancer patients undergoing CCRT.
Abstract
BACKGROUND Complications related to concurrent chemoradiotherapy (CCRT) such as acute radiation-induced esophagitis (ARIE) may cause significant morbidity and unplanned treatment delays in patients with advanced non-small cell lung cancer (NSCLC). We designed a prospective randomized study to assess the impact of glutamine (GLN) supplementation in preventing CCRT-induced toxicities of advanced NSCLC patients. METHODS From September 2014 to September 2015, 60 patients diagnosed with NSCLC were included to the study. Thirty patients (50%) received prophylactic powdered GLN orally at a dose of 10 g/8 h. The prescribed radiation dose to the planning target volume was 30 Gy in 2-Gy fractions. The endpoints were radiation-induced esophagitis, mucositis, body weight loss, overall survival and progression-free survival. RESULTS The 60 patients with NSCLC included 42 men and 18 women with a mean age ± standard deviation of 60.3 years ± 18.2 (range, 44-78 years).At a median follow-up of 26.4 months (range 10.4-32.2), all patients tolerated GLN well. A administration of GLN was associated with a decrease in the incidence of grade 2 or 3 ARIE (6.7% vs 53.4% for Gln+ vs Gln-; P = .004). GLN supplementation appeared to significantly delay ARIE onset for 5.8 days (18.2 days vs 12.4 days; P = .027) and reduced incidence of weight loss (20% vs 73.3%; P = .01). DISCUSSION Our study suggests a beneficial effect of oral glutamine supplementation for the prevention from radiation-induced injury and body weight loss in advanced NSCLC patients who receiving CCRT.
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Fermented Foods: Definitions and Characteristics, Impact on the Gut Microbiota and Effects on Gastrointestinal Health and Disease.
Dimidi, E, Cox, SR, Rossi, M, Whelan, K
Nutrients. 2019;11(8)
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Fermented foods have grown in popularity due to their proposed health benefits but there is limited clinical evidence for the effectiveness of most fermented foods in gastrointestinal health. This review paper looks at non-dairy fermented foods which have been studied in at least one RCT: kefir, sauerkraut, natto, and sourdough bread. The health benefits are attributed to the high ratio of probiotic microorganisms, metabolites, or ability to convert compounds into active metabolites, as well as prebiotics and vitamins contained in these foods. Kimchi has the greatest evidence from epidemiological and case control studies investigating risk of gastric cancers. Different food composition of kimchi is shown to both increase and decrease risks, whilst it had no impact on H. pylori levels. There were no studies on kefir in functional bowel disorders however, it was shown to help lactose malabsorption and reduce H. pylori levels. A small RCT on Sauerkraut showed it reduced IBS severity in patients and increased in vitro activity of key liver and kidney detoxifying enzymes. There are small pockets of data that show that tempeh may influence gut microbiota in humans, and that natto may increase bifidobacterial and short-chain fatty acids in healthy volunteers. There are numerous limited cohort studies on miso and cancer risk but no studies on gastrointestinal conditions. Finally, sourdough was shown to reduce FODMAPS and be better tolerated in IBS patients, reducing bloating, nausea and discomfort. Overall, all the studies provide insufficient evidence on fermented foods and gastrointestinal health.
Abstract
Fermented foods are defined as foods or beverages produced through controlled microbial growth, and the conversion of food components through enzymatic action. In recent years, fermented foods have undergone a surge in popularity, mainly due to their proposed health benefits. The aim of this review is to define and characterise common fermented foods (kefir, kombucha, sauerkraut, tempeh, natto, miso, kimchi, sourdough bread), their mechanisms of action (including impact on the microbiota), and the evidence for effects on gastrointestinal health and disease in humans. Putative mechanisms for the impact of fermented foods on health include the potential probiotic effect of their constituent microorganisms, the fermentation-derived production of bioactive peptides, biogenic amines, and conversion of phenolic compounds to biologically active compounds, as well as the reduction of anti-nutrients. Fermented foods that have been tested in at least one randomised controlled trial (RCT) for their gastrointestinal effects were kefir, sauerkraut, natto, and sourdough bread. Despite extensive in vitro studies, there are no RCTs investigating the impact of kombucha, miso, kimchi or tempeh in gastrointestinal health. The most widely investigated fermented food is kefir, with evidence from at least one RCT suggesting beneficial effects in both lactose malabsorption and Helicobacter pylori eradication. In summary, there is very limited clinical evidence for the effectiveness of most fermented foods in gastrointestinal health and disease. Given the convincing in vitro findings, clinical high-quality trials investigating the health benefits of fermented foods are warranted.
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Cannabidiol in Anxiety and Sleep: A Large Case Series.
Shannon, S, Lewis, N, Lee, H, Hughes, S
The Permanente journal. 2019;23:18-041
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After the psychoactive tetrahydrocannabinol (THC), cannabidiol (CBD) is the second most abundant, and non-psychoactive, cannabinoid of the cannabis plant. CBD appears to have a calming effect on the central nervous system, however, clinical evidence for its use is limited. The purpose of the present study is to describe the effects of CBD on anxiety and sleep. A retrospective chart review of 72 adult patients with primary concerns of anxiety (47 patients) or poor sleep (25 patients) and treated with CBD for at least 1 month as an adjunct to usual treatment, was conducted at a large integrative psychiatric outpatient clinic. Nearly all patients were given CBD 25 mg/d in capsule form. If anxiety complaints predominated, the dosing was every morning, after breakfast. If sleep complaints predominated, the dosing was every evening, after dinner. Monthly visits included clinical evaluation and documentation of patients’ anxiety and sleep status. Whilst anxiety scores showed a rapid and sustained decrease over the three months study period, no sustained improvements in sleep was seen. The treatment with CBD was generally well accepted and tolerated. The authors conclude that these results support the existing scientific evidence, and that more clinical research is needed to provide better clinical guidance on the use of CBD.
Abstract
CONTEXT Cannabidiol (CBD) is one of many cannabinoid compounds found in cannabis. It does not appear to alter consciousness or trigger a "high." A recent surge in scientific publications has found preclinical and clinical evidence documenting value for CBD in some neuropsychiatric disorders, including epilepsy, anxiety, and schizophrenia. Evidence points toward a calming effect for CBD in the central nervous system. Interest in CBD as a treatment of a wide range of disorders has exploded, yet few clinical studies of CBD exist in the psychiatric literature. OBJECTIVE To determine whether CBD helps improve sleep and/or anxiety in a clinical population. DESIGN A large retrospective case series at a psychiatric clinic involving clinical application of CBD for anxiety and sleep complaints as an adjunct to usual treatment. The retrospective chart review included monthly documentation of anxiety and sleep quality in 103 adult patients. MAIN OUTCOME MEASURES Sleep and anxiety scores, using validated instruments, at baseline and after CBD treatment. RESULTS The final sample consisted of 72 adults presenting with primary concerns of anxiety (n = 47) or poor sleep (n = 25). Anxiety scores decreased within the first month in 57 patients (79.2%) and remained decreased during the study duration. Sleep scores improved within the first month in 48 patients (66.7%) but fluctuated over time. In this chart review, CBD was well tolerated in all but 3 patients. CONCLUSION Cannabidiol may hold benefit for anxiety-related disorders. Controlled clinical studies are needed.
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Effectiveness of Vitamin D Supplementation in the Management of Multiple Sclerosis: A Systematic Review.
Berezowska, M, Coe, S, Dawes, H
International journal of molecular sciences. 2019;20(6)
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Epidemiological research shows that Vitamin D status is associated with reduced activity and progression of disease in multiple sclerosis (MS). This review assessed the evidence from ten double-blind randomised controlled trials, including a total of 627 adults with relapsing remitting MS (RRMS), for the clinical effectiveness of vitamin D supplementation compared to placebo in disease and symptom management. The results from the reviewed studies on disease progression and immunological blood parameters were mixed. Where benefits of vitamin D supplementation were seen this tended to be in those groups where vitamin D levels were low at the start of the study. Those studies evaluating the safety and tolerability of vitamin D reported no serious adverse events. The authors conclude that baseline serum vitamin D levels may be a predictor of improvements in RRMS with vitamin D supplementation, and that further research should include baseline vitamin D as part of the assessment.
Abstract
OBJECTIVE to examine the extent of effect vitamin D in Multiple Sclerosis (MS) on pathology and symptoms. METHODS A literature search was performed in November 2018 (CRD42018103615). Eligibility criteria: randomised control trials in English from 2012 to 2018; a clinical diagnosis of MS; interventions containing vitamin D supplementation (vitamin D3 or calcitriol) in disease activity compared to a control/placebo; improvement in: serum 25(OH)D, relapse rates, disability status by Expanded Disability Status Scale (EDSS) scores, cytokine profile, quality of life, mobility, T2 lesion load and new T2 or T1 Gd enhancing lesions, safety and adverse effects. Risk of bias was evaluated. RESULTS Ten studies were selected. The study size ranged from 40 to 94 people. All studies evaluated the use of vitamin D supplementation (ranging from 10 to 98,000 IU), comparing to a placebo or low dose vitamin D. The duration of the intervention ranged from 12 to 96 weeks. One trial found a significant effect on EDSS score, three demonstrated a significant change in serum cytokines level, one found benefits to current enhancing lesions and three studies evaluating the safety and tolerability of vitamin D reported no serious adverse events. Disease measures improved to a greater extent overall in those with lower baseline serum 25(OH)D levels. CONCLUSIONS As shown in 3 out of 10 studies, improvement in disease measures may be more apparent in those with lower baseline vitamin D levels.
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Vitamin D Supplementation in Central Nervous System Demyelinating Disease-Enough Is Enough.
Häusler, D, Weber, MS
International journal of molecular sciences. 2019;20(1)
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Vitamin D is associated with a reduced risk and severity of multiple sclerosis (MS). However, whether supplementing vitamin D level alters disease severity, is a matter of ongoing debate. This review looks at both clinical and pre-clinical evidence for supplementing vitamin D in people with MS. In vitro experiments show that vitamin D and its metabolites can alter function of various immune cells, mostly via interaction with vitamin D receptors (VDR). Results from human clinical trials, however, are mixed. Preclinical evidence suggests that high dose vitamin D supplementation, when leading to hypercalcaemia, a potentially serious side effect of excessive vitamin D intake, may worsen MS. The authors also review research which suggests mechanisms by which sun exposure can improve MS symptoms independent of vitamin D production. The authors conclude that moderate sun exposure, combined with adequate dietary intake of vitamin D, and in conjunction with a regular assessment of vitamin D serum levels (to avoid hypercalcaemia), might be the best strategy for patients with MS.
Abstract
The exact cause of multiple sclerosis (MS) remains elusive. Various factors, however, have been identified that increase an individual's risk of developing this central nervous system (CNS) demyelinating disease and are associated with an acceleration in disease severity. Besides genetic determinants, environmental factors are now established that influence MS, which is of enormous interest, as some of these contributing factors are relatively easy to change. In this regard, a low vitamin D status is associated with an elevated relapse frequency and worsened disease course in patients with MS. The most important question, however, is whether this association is causal or related. That supplementing vitamin D in MS is of direct therapeutic benefit, is still a matter of debate. In this manuscript, we first review the potentially immune modulating mechanisms of vitamin D, followed by a summary of current and ongoing clinical trials intended to assess whether vitamin D supplementation positively influences the outcome of MS. Furthermore, we provide emerging evidence that excessive vitamin D treatment via the T cell-stimulating effect of secondary hypercalcemia, could have negative effects in CNS demyelinating disease. This jointly merges into the balancing concept of a therapeutic window of vitamin D in MS.
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Effect of preoperative immunonutrition on complications after salvage surgery in head and neck cancer.
Mueller, SA, Mayer, C, Bojaxhiu, B, Aeberhard, C, Schuetz, P, Stanga, Z, Giger, R
Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale. 2019;48(1):25
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Surgery, radiotherapy (RT) and chemo-radiotherapy (CRT) are the main treatments for head and neck cancer, but (C)RT has significant side effects on local tissues due to impaired wound healing. Malnutrition is also common in these patients and may add to poor wound healing and recovery. Immunonutrition (IN) are medical dietary formulas designed to provide the essential nutrients for an adequate immune reaction during medical treatment. The aim of this study was to evaluate the effect of preoperative IN on postoperative complications after salvage surgery in head and neck cancer. Patients in the intervention group received 3 IN units per day for 5 days before surgery. The IN units contained 300 kcal and were enriched with omega-3 fatty acids, arginine, RNA-nucleotides and soluble guar fibre. The control group, who did not receive IN, included consecutive patients treated prior to the intervention group. 96 patients were evaluated, of which 51 received IN. The total number of patients suffering any complications was significantly lower in the group receiving IN (35% vs. 58%). There was also a significant reduction in length of hospital stay in the IN group compared to the control group (6 days vs. 17 days). Limitations of this study include the use of a historical control group, and the limited number of patients.
Abstract
BACKGROUND Patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma are at high risk of postoperative complications due to the adverse effects of radiotherapy on wound healing. Malnutrition is an additional risk factor and we tested the hypothesis that preoperative administration of immunonutrition would decrease complications in this high risk population. METHODS This single armed study with historical control included consecutive patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma. We compared outcomes before and after implementation of preoperative immunonutrition and adjusted the regression analysis for gender, age, body mass index, Nutritional Risk Screening (NRS 2002), tobacco and alcohol consumption, tumor localization, tumor stage, and type of surgery. The primary endpoint was overall complications from surgery within a follow-up of 30 days. RESULTS Ninety-six patients were included (intervention group: 51, control group: 45). Use of preoperative immunonutrition was associated with a significant reduction in overall complications (35% vs. 58%, fully-adjusted odds ratio 0.30 (95%CI 0.10-0.91, p = 0.034). Length of hospital stay was also significantly reduced (17 days vs. 6 days, p = < 0.001). No differences in mortality and hospital readmission were found. These results remained robust in multivariate analysis. CONCLUSIONS In patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma, preoperative immunonutrition exhibited favorable effects on the complication rate and consequently reduced the length of hospital stay. By improving both tissue regeneration and immune response, immunonutrition may help to improve surgical outcomes in this high-risk population.
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Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons: A Randomized Placebo-Controlled Trial.
Goncalves-Mendes, N, Talvas, J, Dualé, C, Guttmann, A, Corbin, V, Marceau, G, Sapin, V, Brachet, P, Evrard, B, Laurichesse, H, et al
Frontiers in immunology. 2019;10:65
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This randomized placebo-controlled double-blind trial investigated whether Vit-D supplementation in a sample of 38 deficient elderly persons, over 65-year olds, could improve influenza seroprotection and immune response. Vitamin D is known to both potentiate the innate immune response and inhibit the adaptive system, and so potentially modulate vaccination response. The participants were randomised into two arms: vitamin D supplementation group (D) and placebo group (P). The D group received 100,000 IU/15 days of cholecalciferol over a 3-month period after which both groups were given the influenza vaccine, and their blood was evaluated 28 days later. Several immune biomarkers were analysed including plasma cytokine profiles, phagocyte ROS production, and lymphocyte cells phenotyping to determine if Vitamin D enhanced immune response to the vaccination. No differences were found in serum ROS and antibody markers. However, Vitamin D supplementation did promote a higher TGFβ plasma level in response to influenza vaccination. Taken together, these results suggest that vitamin D supplementation is not an effective way to improve antibody response to influenza vaccine in deficient elderly people.
Abstract
Background: Immunosenescence contributes to reduced vaccine response in elderly persons, and is worsened by deficiencies in nutrients such as Vitamin (Vit-D). The immune system is a well-known target of Vit-D, which can both potentiate the innate immune response and inhibit the adaptive system, and so modulate vaccination response. Objective: This randomized placebo-controlled double-blind trial investigated whether Vit-D supplementation in deficient elderly persons could improve influenza seroprotection and immune response. Design: Deficient volunteers (Vit-D serum <30 ng/mL) were assigned (V1) to receive either 100,000 IU/15 days of cholecalciferol (D, n = 19), or a placebo (P, n = 19), over a 3 month period. Influenza vaccination was performed at the end of this period (V2), and the vaccine response was evaluated 28 days later (V3). At each visit, serum cathelicidin, immune response to vaccination, plasma cytokines, lymphocyte phenotyping, and phagocyte ROS production were assessed. Results: Levels of serum 25-(OH)D increased after supplementation (D group, V1 vs. V2: 20.7 ± 5.7 vs. 44.3 ± 8.6 ng/mL, p < 0.001). No difference was observed for serum cathelicidin levels, antibody titers, and ROS production in D vs. P groups at V3. Lower plasma levels of TNFα (p = 0.040) and IL-6 (p = 0.046), and higher ones for TFGβ (p = 0.0028) were observed at V3. The Th1/Th2 ratio was lower in the D group at V2 (D: 0.12 ± 0.05 vs. P: 0.18 ± 0.05, p = 0.039). Conclusions: Vit-D supplementation promotes a higher TGFβ plasma level in response to influenza vaccination without improving antibody production. This supplementation seems to direct the lymphocyte polarization toward a tolerogenic immune response. A deeper characterization of metabolic and molecular pathways of these observations will aid in the understanding of Vit-D's effects on cell-mediated immunity in aging. This clinical trial was registered at clinicaltrials.gov as NCT01893385.