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关于维生素D有什么前沿研究？
维生素D不仅是强健骨骼的“老帮手”，更在抗癌、调节免疫、保护代谢、延缓衰老和治疗肌肉萎缩等前沿领域展现出巨大潜力。科学家们发现它几乎参与了全身各个系统的运作，但现有的许多健康指南仍停留在只关注骨骼的旧观念上 。
下面为您详细梳理维生素D在各个健康领域的前沿研究，看看这颗“阳光维生素”到底还能为我们的身体做些什么。
1. 打破旧观念：它不仅仅是“骨骼保卫者”
我们以前总觉得，维生素D就是用来帮助身体吸收钙、防止骨质疏松和骨折的。但最新的科学综述指出，现有的很多政府和健康机构的指南过于“以骨骼为中心”了，大大忽略了它在骨骼之外的诸多健康益处 。
研究发现，维生素D对我们的脑部功能、免疫系统、孕期健康、心血管（心脏和血管）健康以及癌症预防都至关重要 。目前有高达四分之一的美国人和百分之六十的中欧人，体内的维生素D水平处于不足状态（低于20 ng/mL）。科学证据强烈建议，应该把血液中的维生素D水平提升到30 ng/mL以上，这能显著降低重大疾病的发生风险和死亡率 。要达到这个目标，每天补充2000 IU（国际单位，50微克）的维生素D是一个可行且有效的方案 。如果想获得更强的保护，甚至可以每天补充4000到6000 IU，让血液水平达到40到70 ng/mL 。
2. 癌症治疗与预防的“新辅助”
前沿研究最令人振奋的领域之一，是维生素D在抗癌方面的表现。它不仅能帮助预防癌症，还能提升现有癌症治疗的效果。
助力乳腺癌化疗： 对于即将接受化疗的乳腺癌患者，补充维生素D带来了意想不到的好消息。有两项重要的临床试验对此进行了研究。第一项试验中，45岁以上的乳腺癌女性患者每天补充2000 IU的维生素D，持续6个月。结果发现，补充维生素D的患者，其肿瘤完全消失（医学上称为“病理完全缓解”）的比例高达43%，而没有补充的对照组只有24% 。另一项更大规模的临床试验也给患者在化疗期间每周补充一次大剂量（50,000 IU）的维生素D。结果同样证实，补充维生素D能显著提高肿瘤完全缓解的概率，让患者获得更好的生存预期 。
调动肠道菌群抗击癌症： 顶级学术期刊《科学》发表的一项研究发现，维生素D能调节肠道里的微生物群落（也就是我们常说的“肠道菌群”），从而增强身体对癌症的免疫力 。在动物实验中，体内维生素D充足的小鼠对癌症的抵抗力更强，并且对免疫治疗（一种通过激活自身免疫系统来杀灭肿瘤的疗法）的反应也更好 。在人类身上同样如此，维生素D相关基因活跃的患者，接受免疫治疗的效果更好，总体生存率也更高 。
普遍的防癌潜力： 一项系统评价指出，血液中充足的维生素D通过减轻炎症、修复基因损伤等机制，能够降低多种癌症的发病率和死亡率，包括结肠癌、胃癌、乳腺癌、卵巢癌等十几种癌症 。研究强调，虽然维持骨骼健康只需血液中维生素D达到20 ng/mL左右，但若想显著降低癌症风险和死亡率，血液水平最好维持在40 ng/mL以上 。
3. 免疫系统的“总调度员”
维生素D在调节免疫系统方面扮演着核心角色，从过敏到自身免疫性疾病，都有它的身影。
对抗过敏性疾病： 过敏性鼻炎、哮喘和特应性皮炎（一种常见的过敏性湿疹）是让人十分苦恼的过敏性疾病。维生素D作为一种脂溶性维生素，在调节免疫系统方面起着关键作用，能够影响这些过敏性疾病的发生和发展过程 。
桥本甲状腺炎： 这是一种免疫系统错误攻击自身甲状腺的疾病。大量文献证实，桥本甲状腺炎患者体内的维生素D水平明显低于健康人 。当给这些缺乏维生素D的患者补充维生素D后，他们体内攻击自身甲状腺的抗体指标显著下降了 。
1型糖尿病： 1型糖尿病也是一种免疫系统攻击自身细胞（胰腺中分泌胰岛素的细胞）的疾病。虽然研究发现维生素D缺乏在刚确诊的1型糖尿病儿童中更为普遍，且作为辅助治疗能在短期内起到一定积极作用，但目前还没有证据表明它能直接预防1型糖尿病的发生 。
肠道与皮肤的健康桥梁： 科学家提出了“肠-皮肤轴”的概念，即肠道和皮肤之间通过微生物群落进行双向交流 。维生素D受体在这一过程中至关重要，肠道菌群的平衡不仅维护肠道健康，还能防止皮肤发炎 。此外，维生素D还能帮助修复受损的肠道屏障，防止肠道内的有害物质漏到血液中引发炎症 。
4. 代谢与肌肉的“强心剂”
维生素D对人体的新陈代谢和肌肉力量同样至关重要。
改善糖尿病与代谢健康： 在2024年举行的第八届维生素D争议国际会议上，专家们重点讨论了维生素D对代谢健康的影响 。研究显示，低水平的维生素D与心血管疾病和糖尿病风险增加密切相关 。对于处于糖尿病前期（血糖已经偏高，但还没达到糖尿病标准）的成年人，补充维生素D不仅有助于改善血糖，还能降低其发展为真正糖尿病的风险，甚至增加血糖恢复正常的机会 。
对抗肌肉萎缩（肌少症）： 肌少症是一种随着年龄增长，骨骼肌质量和力量不断流失的疾病，会导致人虚弱无力，增加死亡风险 。正常情况下，人在40岁以后每十年会流失约8%的肌肉，70岁后更是加速到每十年流失15% 。但最新研究打破了这个旧观念：研究发现，由于缺乏运动、营养不良、缺乏维生素D等原因，现在每10个年轻人中就有超过1个患有肌少症 。维生素D作为一种关键的营养补充剂，与其他营养物质（如蛋白质、Omega-3脂肪酸）结合，能有效支持肌肉健康 。不仅如此，维生素D还能调节肌肉的线粒体（可以看作是细胞内的“发电厂”，负责产生能量）功能，防止肌肉衰弱 。
运动员的健康密码： 对于运动员来说，维生素D和镁是黄金搭档。维生素D不仅帮助吸收钙、防止骨折，还能维持肌肉功能、减少呼吸道感染 。镁则在肌肉收缩、能量产生中不可或缺。更奇妙的是，维生素D能帮助身体吸收镁，而镁又是合成和激活维生素D所必需的，两者相辅相成 。
5. 神经退行性疾病与抗衰老的“新希望”
随着年龄增长，大脑老化和身体机能衰退是不可避免的，但维生素D可能在这个过程踩下“刹车”。
保护大脑神经： 帕金森病、阿尔茨海默病（老年痴呆）等神经退行性疾病，往往伴随着细胞内“发电厂”（线粒体）功能障碍 。科学家提出，补充辅酶Q10、B族维生素、维生素D等特定营养素，可以帮助恢复线粒体功能，从而对这类大脑退化性疾病产生潜在益处 。对于绝经后的女性，由于体内多种营养素流失，患神经退行性疾病（如帕金森、阿尔茨海默病、认知衰退）的风险增加，维持充足的维生素D水平被认为是保持大脑健康的关键一环 。
提升“抗衰老蛋白”： 科学家发现了一种名为“Klotho”的蛋白质，它被称为“抗衰老蛋白”。体内缺乏这种蛋白质的小鼠会未老先衰、寿命缩短；而让这种蛋白质过度表达，则能延长寿命 。在人体中，这种蛋白质的水平会随着年龄增长而下降 。令人惊喜的是，临床实验发现，补充维生素D（以及某些降压药、降脂药）能够提升血液中这种“抗衰老蛋白”的水平 。这意味着维生素D在延缓全身衰老、保护肾脏和心血管方面，可能有着深远的潜力。
6. 特殊人群的专属呵护
除了上述领域，维生素D在一些特定人群中也发挥着独特作用。
- 烧伤患者： 研究发现，几乎所有烧伤的儿童和大多数烧伤的成年人，体内维生素D水平都很低 。充足的维生素D能调节免疫和心血管活动，对烧伤患者的恢复大有益处。不过，目前对于烧伤患者该用多少剂量、怎么用，还需要更多研究来确定 。
- 银屑病（牛皮癣）患者： 这是一种慢性的免疫介导的皮肤病。目前治疗银屑病的外用药物中，维生素D类似物（结构和功能类似于维生素D的物质）就是非常主流且有效的一线选择 。
- 绝经后女性： 绝经后的女性由于雌激素下降，面临心血管疾病、骨质疏松、肥胖等多种健康风险 。保持均衡饮食和充足的维生素D水平，对于维持她们的生活质量、预防慢性疾病至关重要 。
总结：潜力巨大，但仍需精准探索
综上所述，维生素D早已不是那个只管骨骼的单一营养素，它深度参与了我们的抗癌免疫、代谢调节、神经保护和抗衰老过程。
然而，我们也要客观看到，虽然大量的观察性研究支持维生素D的广泛益处，但一些大规模的随机对照试验（最高级别的证据）有时却得不出一致结论 。科学家们指出，这往往是因为过去的研究设计存在缺陷，比如招募的受试者本身维生素D就不缺、给的剂量太小、或者观察时间太短 。
因此，未来的研究方向是开展针对特定疾病、个性化剂量的高质量临床试验 。在日常生活中，确保自己血液中的维生素D水平达到30 ng/mL以上（特别是达到40-70 ng/mL的较优区间），可能是迈向全身健康的一项明智投资 。
References
1Vitamin D: Evidence-Based Health Benefits and Recommendations for Population Guidelines.PubMed
William B Grant, Sunil J Wimalawansa, Pawel Pludowski, et al.
Vitamin D offers numerous under-recognized health benefits beyond its well-known role in musculoskeletal health. It is vital for extra-renal tissues, prenatal health, brain function, immunity, pregnancy, cancer prevention, and cardiovascular health. Existing guidelines issued by governmental and health organizations are bone-centric and largely overlook the abovementioned extra-skeletal benefits and optimal thresholds for vitamin D. In addition, they rely on randomized controlled trials (RCTs), which seldom show benefits due to high baseline 25-hydroxyvitamin D [25(OH)D] concentrations, moderate supplementation doses, and flawed study designs. This review emphasizes the findings from prospective cohort studies showing that higher 25(OH)D concentrations reduce the risks of major diseases and mortality, including pregnancy and birth outcomes. Serum concentrations > 30 ng/mL (75 nmol/L) significantly lower disease and mortality risks compared to <20 ng/mL. With 25% of the U.S. population and 60% of Central Europeans having levels <20 ng/mL, concentrations should be raised above 30 ng/mL. This is achievable through daily supplementation with 2000 IU/day (50 mcg/day) of vitamin D, which prevent diseases and deaths. Furthermore, a daily dose between 4000 and 6000 IU of vitamin D to achieve serum 25(OH)D levels between 40 and 70 ng/mL would provide greater protection against many adverse health outcomes. Future guidelines and recommendations should integrate the findings from observational prospective cohort studies and well-designed RCTs to improve public health and personalized care.
2Vitamin D in burn-injured patients.PubMed
Megan A Rech, Daniel Colon Hidalgo, Jennifer Larson, et al.
Recently, many studies have demonstrated pleotropic effects of vitamin D, including immune modulation and cardiovascular system activity. Sufficient vitamin D concentrations and supplementation of vitamin D may be of benefit in burn-injured patients. Low 25(OH)D has been observed in nearly all pediatric and most adult burn patients. Vitamin D has primarily been studied in pediatric burn patients, focusing on bone marker measurements and the incidence of fractures. The preferred vitamin D dose, formulation, and route of administration remain unknown, and there is limited data on the impact of vitamin D status on clinical outcomes. Further research should focus on determining optimal monitoring strategies, supplementation regimens and clinical outcomes like mortality, length of stay and incidence of sepsis.
3Consensus statement on vitamin D role in metabolic health.PubMed
Andrea Giustina, Luigi di Filippo, Aneta Aleksova, et al.
The 8th International Conference Controversies in Vitamin D, held in September 2024, convened leading experts to address the multifaceted role of vitamin D in human health. Key discussions focused on its influence on metabolic health, including effects on sarcopenia, muscle function, and energy metabolism, as well as its role in obesity, cardiovascular health, and diabetes. Preclinical evidence was presented, suggesting a pivotal role of vitamin D in regulating muscle function and repair, potentially preventing sarcopenia. A relationship between low vitamin D (25[OH]D) concentrations and increased risk of cardiovascular diseases and diabetes was supported by several preclinical and clinical studies. Vitamin D supplementation was recently demonstrated to help improve glycemia and reduce the progression to diabetes and increase the likelihood of regression to normal glucose regulation in adults with prediabetes. Despite mixed outcomes from large, population-based randomized clinical trials, the conference underscored the critical need for personalized research, through disease-specific clinical trials, to fully elucidate the therapeutic potential of vitamin D supplementation, particularly in chronic conditions such as cardiovascular diseases and diabetes. In conclusion, while vitamin D demonstrates considerable promise in modifying a wide array of metabolic health concerns, rigorous scientific inquiry is essential to deepen our understanding of its mechanisms as well as potential protective effects and establish evidence-based guidelines for supplementation. This growing body of work has the potential to significantly enhance clinical outcomes and improve public health strategies, calling for continued exploration and collaboration in the field of vitamin D research.
4Mitochondrial Dysfunction and Neurodegenerative Disorders: Role of Nutritional Supplementation.PubMed
David Mantle, Iain Parry Hargreaves
Mitochondrial dysfunction has been implicated in the pathogenesis of a number of neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, multisystem atrophy, and progressive supranuclear palsy. This article is concerned specifically with mitochondrial dysfunction as defined by reduced capacity for ATP production, the role of depleted levels of key nutritionally related metabolites, and the potential benefit of supplementation with specific nutrients of relevance to normal mitochondrial function in the above neurodegenerative disorders. The article provides a rationale for a combination of CoQ10, B-vitamins/NADH, L-carnitine, vitamin D, and alpha-lipoic acid for the treatment of the above neurodegenerative disorders.
5Vitamin D regulates microbiome-dependent cancer immunity.PubMed
Evangelos Giampazolias, Mariana Pereira da Costa, Khiem C Lam, et al.
A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of , which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.
6Vitamin D and allergic diseases.PubMed
Panyu Zhang, Qingxiu Xu, Rongfei Zhu
In recent years, the relationship between vitamin D and allergic diseases has received widespread attention. As a fat-soluble vitamin, vitamin D plays a crucial role in regulating the immune system and may influence the onset and progression of diseases such as atopic dermatitis, allergic rhinitis, and asthma. To understand the underlying mechanisms, we have summarized the current research on the association between vitamin D and allergic diseases. We also discuss the impact of vitamin D on the immune system and its role in the course of allergic diseases, particularly focusing on how vitamin D supplementation affects the treatment outcomes of these conditions. We aim to provide a theoretical basis and practical guidance for optimizing the management and treatment of allergic diseases by modulating vitamin D levels.
7Advances in muscle health and nutrition: A toolkit for healthcare professionals.PubMed
Carla M Prado, Francesco Landi, Samuel T H Chew, et al.
Low muscle mass and malnutrition are prevalent conditions among adults of all ages, with any body weight or body mass index, and with acute or chronic conditions, including COVID-19. This article synthesizes the latest research advancements in muscle health and malnutrition, and their impact on immune function, and clinical outcomes. We provide a toolkit of illustrations and scientific information that healthcare professionals can use for knowledge translation, educating patients about the importance of identifying and treating low muscle mass and malnutrition. We focus on the emerging evidence of mitochondrial dysfunction in the context of aging and disease, as well as the cross-talk between skeletal muscle and the immune system. We address the importance of myosteatosis as a component of muscle composition, and discuss direct, indirect and surrogate assessments of muscle mass including ultrasound, computerized tomography, deuterated creatine dilution, and calf circumference. Assessments of muscle function are also included (handgrip strength, and physical performance tests). Finally, we address nutrition interventions to support anabolism, reduce catabolism, and improve patient outcomes. These include protein and amino acids, branched-chain amino acids, with a focus on leucine; β-hydroxy-β-methylbutyrate (HMB), vitamin D; n-3 polyunsaturated fatty acids (n-3 PUFA), polyphenols, and oral nutritional supplements. We concluded with recommendations for clinical practice and a call for action on research focusing on evaluating the impact of body composition assessments on targeted nutrition interventions, and consequently their ability to improve patient outcomes.
8Vitamin D Supplementation Improves Pathological Complete Response in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy: A Randomized Clinical Trial.PubMed
Michelle Sako Omodei, Jackeline Chimicoviaki, Daniel Araujo Brito Buttros, et al.
UNLABELLED: This study aimed to evaluate the effect of vitamin D (VD) supplementation on the pathological complete response (pCR) rate in women with breast cancer (BC) undergoing neoadjuvant chemotherapy (NCT). A randomized clinical trial was conducted with 80 women aged ≥45years with BC who were eligible for NCT. Women were randomized into two groups: VD group, daily supplementation with 2,000IU of cholecalciferol ( = 40) or placebo ( = 40), for 6 months. The primary outcome measure was the pCR rate. Serum 25-hydroxyvitamin-D [25(OH)D] levels were measured after BC diagnosis and the end of NCT. Of the 80 randomized women, 75 completed the NCT and underwent surgery. Baseline 25(OH)D values indicated hypovitaminosis D in both groups (VD: 19.6 ± 5.8 ng/mL and placebo: 21 ± 7.9 ng/mL, = 0.33). After 6 months, 25(OH)D levels increased in the VD group compared to the placebo group (28 ± 8.7 vs. 20.2 ± 6.1 ng/mL, = 0.03). The pCR rate was higher in women supplemented with VD when compared than the placebo (43% vs. 24%, = 0.04). Adjusted logistic regression showed that women with 25(OH)D levels ≥20ng/mL were more likely to achieve pCR (OR3.65, 95%CI 1.09-12.8, = 0.04). Women with BC undergoing NCT who received supplementation with 2,000IU of VD were more likely to achieve a pathological complete response than women in the placebo group. TRIAL REGISTRATION: Ensaiosclinicos.gov.br, identifier RBR-10k4gqdg.
9A systematic review on the impact of nutrition and possible supplementation on the deficiency of vitamin complexes, iron, omega-3-fatty acids, and lycopene in relation to increased morbidity in women after menopause.PubMed
Friederike Wylenzek, Kai J Bühling, Elena Laakmann
UNLABELLED: A balanced and healthy diet during the menopausal transition and after menopause is crucial for women to reduce the risk for morbidities and chronic diseases due to deficiency of essential nutrients. PURPOSE: The objective of this study was to conduct a systematic review of studies that analyzed the impact of vitamin and nutrient deficiencies in postmenopausal women in relation to increased morbidities and chronic conditions. METHODS: Observational studies were searched in the databases PubMed, UpToDate, and Google Scholar. RESULTS: We searched 122 studies, of which 90 were included in our analysis. The meta-analysis of the data could not be performed because of the heterogeneity of the statistical methods in the included studies. In our study, we focused on the aspects of vitamin B6, vitamin B12, vitamin D, iron, omega-3-fatty acids, and lycopene, belonging to the family of carotenoids. Postmenopausal women with deficiencies of these nutrients are more vulnerable to comorbidities such as cardiovascular and cerebrovascular events, metabolic diseases, osteoporosis, obesity, cancer and neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, depression, cognitive decline, dementia, and stroke. We concluded that women after menopause tend to have a greater probability of suffering from deficiencies in various vitamins and nutrients, and consequently have an increased risk of developing morbidities and chronic diseases. CONCLUSION: In conclusion, maintaining optimum serum levels of nutrients and vitamins, either through a balanced and healthy diet consuming fresh fruits, vegetables, and fats or by taking appropriate supplementation, is essential in maintaining optimal health-related quality of life and reducing the risk for women during the menopausal transition and after menopause. Nevertheless, more recent studies need to be assessed to formulate adequate recommendations to achieve positive clinical outcomes.
10The gut-skin axis: a bi-directional, microbiota-driven relationship with therapeutic potential.PubMed
Maira Jimenez-Sanchez, Larissa S Celiberto, Hyungjun Yang, et al.
This review explores the emerging term "gut-skin axis" (GSA), describing the bidirectional signaling that occurs between the skin and the gastrointestinal tract under both homeostatic and disease conditions. Central to GSA communication are the gut and skin microbiota, the microbial communities that colonize these barrier surfaces. By influencing diverse host pathways, including innate immune, vitamin D receptor, and Aryl hydrocarbon receptor signaling, a balanced microbiota contributes to both tissue homeostasis and host defense. In contrast, microbiota imbalance, or dysbiosis at one site, can lead to local barrier dysfunction, resulting in the activation of signaling pathways that can disrupt tissue homeostasis at the other site, potentially leading to inflammatory skin conditions such as atopic dermatitis and psoriasis, or gut diseases like Inflammatory Bowel Disease. To date, most research on the GSA has examined the impact of the gut microbiota and diet on skin health, but recent studies show that exposing the skin to ultraviolet B-light can beneficially modulate both the gut microbiome and intestinal health. Thus, despite the traditional focus of clinicians and researchers on these organ systems as distinct, the GSA offers new opportunities to better understand the pathogenesis of cutaneous and gastrointestinal diseases and promote health at both sites.
11The Importance of Vitamin D and Magnesium in Athletes.PubMed
Ligia J Dominguez, Nicola Veronese, Francesco Saverio Ragusa, et al.
Vitamin D and magnesium are essential nutrients that play key roles in an athlete's performance, recovery, and overall health. Vitamin D is crucial for bone health (aiding calcium absorption and preventing stress fractures), muscle function (preventing weakness and injury), and reducing respiratory infections. Magnesium is fundamental in muscle function, adenosine triphosphate production for muscle contraction, electrolyte balance, bone strength, and cardiovascular health. The magnesium requirement of healthy adults is estimated at 300-400 mg/day, but there is evidence that athletes may have higher magnesium needs compared to sedentary persons. Magnesium and vitamin D are closely linked-vitamin D aids magnesium absorption, while magnesium is vital for vitamin D synthesis, transport, and activation. Given their importance in athletes, this article explores their functions, interactions, and the effects of deficiencies and supplementation in athletic populations.
12Psoriasis: a brief overview.PubMed
Antony Raharja, Satveer K Mahil, Jonathan N Barker
Psoriasis is a clinically heterogeneous lifelong skin disease that presents in multiple forms such as plaque, flexural, guttate, pustular or erythrodermic. An estimated 60 million people have psoriasis worldwide, with 1.52% of the general population affected in the UK. An immune-mediated inflammatory disease, psoriasis has a major genetic component. Its association with psoriatic arthritis and increased rates of cardiometabolic, hepatic and psychological comorbidity requires a holistic and multidisciplinary care approach. Psoriasis treatments include topical agents (vitamin D analogues and corticosteroids), phototherapy (narrowband ultraviolet B radiation (NB-UVB) and psoralen and ultraviolet A radiation (PUVA)), standard systemic (methotrexate, ciclosporin and acitretin), biologic (tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors) or small molecule inhibitor (dimethyl fumarate and apremilast) therapies. Advances in the understanding of its pathophysiology have led to development of highly effective and targeted treatments.
13Vitamin D's Impact on Cancer Incidence and Mortality: A Systematic Review.PubMed
Sunil J Wimalawansa
: Adequate vitamin D levels are essential for various physiological functions, including cell growth, immune modulation, metabolic regulation, DNA repair, and overall health span. Despite its proven cost-effectiveness, widespread deficiency persists due to inadequate supplementation and limited sunlight exposure. : This systematic review (SR) examines the relationship between vitamin D and the reduction of cancer risk and mortality, and the mechanisms involved in cancer prevention. This SR followed the PRISMA and PICOS guidelines and synthesized evidence from relevant studies. : Beyond genomic actions via calcitriol [1,25(OH)D]-receptor interactions, vitamin D exerts cancer-protective effects through mitigating inflammation, autocrine, paracrine, and membrane signaling. The findings reveal a strong inverse relationship between serum 25(OH)D levels and the incidence, metastasis, and mortality of several cancer types, including colon, gastric, rectal, breast, endometrial, bladder, esophageal, gallbladder, ovarian, pancreatic, renal, vulvar cancers, and both Hodgkin's and non-Hodgkin's lymphomas. While 25(OH)D levels of around 20 ng/mL suffice for musculoskeletal health, maintaining levels above 40 ng/mL (100 nmol/L: range, 40-80 ng/mL) significantly lowers cancer risks and mortality. : While many observational studies support vitamin D's protective role in incidents and deaths from cancer, some recent mega-RCTs have failed to demonstrate this. The latter is primarily due to critical study design flaws, like recruiting vitamin D sufficient subjects, inadequate dosing, short durations, and biased designs in nutrient supplementation studies. Consequently, conclusions from these cannot be relied upon. Well-designed, adequately powered clinical trials using appropriate methodologies, sufficient vitamin D doses, and extended durations consistently demonstrate that proper supplementation significantly reduces cancer risk and markedly lowers cancer mortality.
14An Overview of Sarcopenia: Focusing on Nutritional Treatment Approaches.PubMed
Michele Barone, Palmina Baccaro, Alessio Molfino
Sarcopenia is a syndrome characterized by the progressive and generalized loss of skeletal muscle mass and strength. This condition is associated with physical disability, decreased quality of life, and increased mortality. Therefore, reducing the prevalence of sarcopenia could significantly lower healthcare costs. Sarcopenia can be classified into primary and secondary sarcopenia. The former is related to aging and begins after the fourth decade of life; after that, there is a muscle loss of around 8% per decade until age 70 years, which subsequently increases to 15% per decade. On the other hand, secondary sarcopenia can affect all individuals and may result from various factors including physical inactivity, malnutrition, endocrine disorders, neurodegenerative diseases, inflammation, and cachexia. Understanding the multiple mechanisms involved in the onset and progression of sarcopenia allows for us to develop strategies that can prevent, treat, or at least mitigate muscle loss caused by increased protein breakdown. One potential treatment of sarcopenia is based on nutritional interventions, including adequate caloric and protein intake and specific nutrients that support muscle health. Such nutrients include natural food rich in whey protein and omega-3 fatty acids as well as nutritional supplements like branched-chain amino acids, β-hydroxy-β-methylbutyrate, and vitamin D along with food for special medical purposes. It is important to emphasize that physical exercises, especially resistance training, not only promote muscle protein synthesis on their own but also work synergistically with nutritional strategies to enhance their effectiveness.
15Intestinal Barrier Impairment, Preservation, and Repair: An Update.PubMed
Ayah Matar, John A Damianos, Kara J Jencks, et al.
BACKGROUND/OBJECTIVES: Our objective was to review published studies of the intestinal barrier and permeability, the deleterious effects of dietary components (particularly fat), the impact of altered intestinal permeability in disease models and human diseases, the role of the microbiome and epigenomics in control of barrier function, and the opportunities to restore normal barrier function with dietary interventions and products of the microbiota. METHODS: We conducted a literature review including the following keywords alone or in combination: intestinal barrier, permeability, microbiome, epigenomics, diet, irritable bowel syndrome, inflammatory bowel disease, probiotics. RESULTS: Intestinal permeability is modified by a diet including fat, which increases permeability, and nutrients such as fiber, glutamine, zinc, vitamin D, polyphenols, emulsifiers, and anthocyanins, which decrease permeability. There is significant interaction of the microbiome and barrier function, including the inflammatory of luminal/bacterial antigens, and anti-inflammatory effects of commensals or probiotics and their products, including short-chain fatty acids. Epigenomic modification of barrier functions are best illustrated by effects on junction proteins or inflammation. Detailed documentation of the protective effects of diet, probiotics, prebiotics, and microbiota is provided. CONCLUSION: intestinal permeability is a critical factor in protection against gastrointestinal diseases and is impacted by nutrients that preserve or heal and repair the barrier and nurture anti-inflammatory effects.
16Autoimmune Thyroiditis and Vitamin D.PubMed
Teodoro Durá-Travé, Fidel Gallinas-Victoriano
Hashimoto's thyroiditis (HT) is marked by self-tissue destruction as a consequence of an alteration in the adaptive immune response that entails the evasion of immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review of the relationship between vitamin D status and HT and the role of vitamin D supplementation in reducing HT risk by modulating the immune system. There is extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titers decreased significantly. Further knowledge of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases requires the execution of additional randomized, double-blind, placebo-controlled trials and longer follow-up periods.
17Vitamin D Supplementation During Neoadjuvant Chemotherapy for Breast Cancer Improves Pathological Complete Response: A Prospective Randomized Clinical Trial.PubMed
Enver Özkurt, Cetin Ordu, Tolga Özmen, et al.
INTRODUCTION: Achieving a pCR serves as a biomarker indicating enhanced overall survival for breast cancer patients undergoing NST. Vitamin D enhances the antitumor effect of chemotherapeutics as demonstrated in cancer cells and animal models. In this prospective randomized clinical study, we aim to investigate the effect of oral vitamin D supplementation during neoadjuvant systemic therapy (NST) on pathologic complete response (pCR). METHODS: Between June 2019 and June 2023, an oral form of 50,000 IU vitamin D3 (cholecalciferol) replacement was administered once a week during NST for the study group. RESULTS: There were 114 (50.2%) cases in the study group and 113 (49.8%) in the control group (totally 227 cases). Factors that positively influenced pCR were higher clinical T stage, higher AJCC clinical stage, Estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, high Ki-67 expression (≥ 20%), hormone negative molecular subtypes, and vitamin D intake in univariate analysis. In the multivariate analysis, factors significantly affecting pCR were vitamin D intake (OR: 2.33, 95% CI 1.20-4.53; p = 0.013), hormone receptor negativity (OR: 2.22, 95% CI 1.11-4.43; p = 0.024), and Ki-67 ≥ 20% (OR: 3.27, 95% CI 1.03-10.34; p = 0.044). CONCLUSIONS: This is the first and only study to compare the effect of oral vitamin D supplementation on pCR during NST. Vitamin D supplementation during NST has a significant effect on pCR in breast cancer patients. Although this effect is not significant for axillary pCR, there is an almost significant correlation. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT03986268).
18Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations.PubMed
Gérald J Prud'homme, Mervé Kurt, Qinghua Wang
The α-Klotho protein (henceforth denoted Klotho) has antiaging properties, as first observed in mice homozygous for a hypomorphic gene (). These mice have a shortened lifespan, stunted growth, renal disease, hyperphosphatemia, hypercalcemia, vascular calcification, cardiac hypertrophy, hypertension, pulmonary disease, cognitive impairment, multi-organ atrophy and fibrosis. Overexpression of Klotho has opposite effects, extending lifespan. In humans, Klotho levels decline with age, chronic kidney disease, diabetes, Alzheimer's disease and other conditions. Low Klotho levels correlate with an increase in the death rate from all causes. Klotho acts either as an obligate coreceptor for fibroblast growth factor 23 (FGF23), or as a soluble pleiotropic endocrine hormone (s-Klotho). It is mainly produced in the kidneys, but also in the brain, pancreas and other tissues. On renal tubular-cell membranes, it associates with FGF receptors to bind FGF23. Produced in bones, FGF23 regulates renal excretion of phosphate (phosphaturic effect) and vitamin D metabolism. Lack of Klotho or FGF23 results in hyperphosphatemia and hypervitaminosis D. With age, human renal function often deteriorates, lowering Klotho levels. This appears to promote age-related pathology. Remarkably, Klotho inhibits four pathways that have been linked to aging in various ways: Transforming growth factor β (TGF-β), insulin-like growth factor 1 (IGF-1), Wnt and NF-κB. These can induce cellular senescence, apoptosis, inflammation, immune dysfunction, fibrosis and neoplasia. Furthermore, Klotho increases cell-protective antioxidant enzymes through Nrf2 and FoxO. In accord, preclinical Klotho therapy ameliorated renal, cardiovascular, diabetes-related and neurodegenerative diseases, as well as cancer. s-Klotho protein injection was effective, but requires further investigation. Several drugs enhance circulating Klotho levels, and some cross the blood-brain barrier to potentially act in the brain. In clinical trials, increased Klotho was noted with renin-angiotensin system inhibitors (losartan, valsartan), a statin (fluvastatin), mTOR inhibitors (rapamycin, everolimus), vitamin D and pentoxifylline. In preclinical work, antidiabetic drugs (metformin, GLP-1-based, GABA, PPAR-γ agonists) also enhanced Klotho. Several traditional medicines and/or nutraceuticals increased Klotho in rodents, including astaxanthin, curcumin, ginseng, ligustilide and resveratrol. Notably, exercise and sport activity increased Klotho. This review addresses molecular, physiological and therapeutic aspects of Klotho.
19Sarcopenia in youth.PubMed
Han Na Jung, Chang Hee Jung, You-Cheol Hwang
Recent research has revealed causes other than aging that may induce sarcopenia in young people, contrary to the long-studied age-dependent reduction in muscular mass and function. The risk of sarcopenia begins in early adulthood, resulting in exaggerated muscle dysfunction in later life. Despite its clinical significance, research on youth-onset sarcopenia is still in its infancy. Due to a paucity of epidemiologic data and standardized criteria for sarcopenia in youth, determining the prevalence of sarcopenia in the young population remains challenging. Based on the evidence, >1 in every 10 young adults of most ethnicities is estimated to have sarcopenia. This review summarizes the possible etiologies of sarcopenia in young populations, including metabolic syndrome, physical inactivity, inadequate nutrition, inherent and perinatal factors, vitamin D deficiency, endocrinopathy, an imbalance of gut microbiota, neuromuscular diseases, organ failure, malignancy, and other inflammatory disorders. This is the first review of the current knowledge on the importance, prevalence, diagnosis, and causes of sarcopenia in youth.
20Type 1 Diabetes Mellitus and Vitamin D.PubMed
Teodoro Durá-Travé, Fidel Gallinas-Victoriano
Type 1 diabetes mellitus (T1DM) is a multifactorial disease in which environmental factors and genetic predisposition interact to induce an autoimmune response against pancreatic β-cells. Vitamin D promotes immune tolerance through immunomodulatory and anti-inflammatory functions. The aim of this study is to provide a narrative review about the association between vitamin D status in the pathogenesis of T1DM and the role of vitamin D supplementation in the prevention and treatment of T1DM. Although vitamin D deficiency is more prevalent in children/adolescents with new-onset T1DM than in healthy individuals, there does not appear to be an association between vitamin D status before diagnosis and the onset of T1DMD later in life. The results of vitamin D as adjuvant therapy have, at best, a positive short-term effect in newly diagnosed T1DM patients. Intervention studies have been conducted in the clinical phase of T1DM, but it would be desirable to do so in the early stages of the autoimmune process (pre-diabetes).