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Fat-Soluble Vitamins for Disease Prevention and Management

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 32186

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Prof. Dr. Caroline S. Stokes

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1. Food and Health Research Group, Faculty of Life Sciences, Humboldt University of Berlin, 14195 Berlin, Germany
2. Department of Molecular Toxicology, German Institute of Human Nutrition, 14558 Potsdam-Rehbruecke, Germany
Interests: vitamin D metabolism; fat-soluble vitamins; microbiome; liver diseases; depression; sustainable nutrition
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Special Issue Information

Dear Colleagues,

In this Special Issue of Nutrients, we would like to bring together papers focusing on the topic of the influence of fat-soluble vitamins (A, D, E and K) on health outcomes. Fat-soluble micronutrient deficiencies have been associated with unfavourable health outcomes and various diseases such as cancer, diabetes, cardiovascular and liver diseases.

Fat-soluble vitamins have a multitude of functions, including important immunomodulatory, inflammatory, and antioxidant-related processes, and deficiencies in these vitamins can contribute to, amongst others, the weakening of the immune system.

Fat-soluble vitamins are stored in the body and unlike water-soluble vitamins, cannot easily be excreted. Consequently, higher than required concentrations of such vitamins can be harmful. There is growing interest in the influence of fat-soluble micronutrients in both the prevention and management of disease. This interest is driven by the knowledge of the many biochemical functions of these essential nutrients but also by emerging pleiotropic processes.

These considerations warrant a Special Issue on fat-soluble vitamins to highlight recent developments in basic and applied research into their role in health maintenance as well as to shed more light on any controversial issues. Manuscripts presenting basic, applied, and clinical research, observational, and meta-analysis studies, and analytical reviews in the fat-soluble vitamins area are encouraged for this Special Issue.

Prof. Dr. Caroline Stokes
Guest Editor

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Keywords

fat-soluble vitamins
neuropsychiatry
ageing
vitamin A
vitamin D
vitamin E
vitamin K
non-alcoholic fatty liver disease
cancer
diabetes
immune function
CVD

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Published Papers (10 papers)

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Research

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20 pages, 476 KiB

Open AccessArticle

Minipuberty in Sons of Women with Low Vitamin D Status during Pregnancy

by Karolina Kowalcze, Robert Krysiak and Anna Obuchowicz

Nutrients 2023, 15(22), 4729; https://doi.org/10.3390/nu15224729 - 9 Nov 2023

Cited by 5 | Viewed by 1437

Abstract

Minipuberty is a transient phase of reproductive axis activation during the first several months of life, playing an important role in the development of reproductive organs in boys. Low 25-hydroxyvitamin D levels during pregnancy are associated with an increased risk of neonatal complications. An inadequate gestational vitamin D status is hypothesized to affect the postnatal activation of the hypothalamic–pituitary–gonadal axis. The purpose of our study was to assess whether a low vitamin D status during pregnancy determines the course of minipuberty in boys. The study included three groups of male infants born to women with different vitamin D statuses: sons of women with vitamin D deficiency (group 1), sons of women with vitamin D insufficiency (group 2), and male offspring of females with normal 25-hydroxyvitamin D levels (group 3 (the reference group)). Concentrations of testosterone, androstenedione, dehydroepiandrosterone sulfate, estradiol, progesterone, and 17-hydroxyprogesterone in saliva, as well as concentrations of gonadotropins in urine, were assayed monthly from postnatal months 1 to 6, and once every 2 months in the second half of the first year of life. Additionally, at each visit, penile length and testicular volume were assessed. Concentrations of testosterone, FSH, and LH, as well as penile length and testicular volume, were greater in group 1 than in groups 2 and 3. In turn, group 2 was characterized by higher FSH levels and a greater testicular volume than group 3. Peak concentrations of LH and testosterone were observed earlier in group 1 than in the remaining groups. The obtained results suggest that a low vitamin D status during pregnancy may have a stimulatory impact on reproductive axis activity and on the early postnatal development of male genital organs, correlating with the severity of hypovitaminosis D. Full article

(This article belongs to the Special Issue Fat-Soluble Vitamins for Disease Prevention and Management)

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17 pages, 593 KiB

Open AccessArticle

Sexual Function and Depressive Symptoms in Young Women with Euthyroid Hashimoto’s Thyroiditis Receiving Vitamin D, Selenomethionine and Myo-Inositol: A Pilot Study

by Robert Krysiak, Karolina Kowalcze, Witold Szkróbka and Bogusław Okopień

Nutrients 2023, 15(12), 2815; https://doi.org/10.3390/nu15122815 - 20 Jun 2023

Cited by 3 | Viewed by 2269

Abstract

Thyroid autoimmunity is associated with an increased risk of sexual dysfunction. The aim of this study was to compare sexual functioning and depressive symptoms in women with Hashimoto’s thyroiditis receiving different treatments. The study included euthyroid women with autoimmune thyroiditis, untreated or receiving vitamin D, selenomethionine, or myo-inositol. Apart from measuring antibody titers and hormone levels, all participants completed questionnaires evaluating female sexual function (FSFI) and depressive symptoms (BDI-II). In untreated women, the overall FSFI scores and domain scores for desire, arousal, lubrication, and sexual satisfaction were lower than in women receiving vitamin D, selenomethionine, and myo-inositol. In the vitamin D-treated women, the total FSFI scores and scores for desire and arousal were higher than in women receiving the remaining micronutrients. The BDI-II score was lowest in the vitamin D-treated women and highest in the untreated patients with thyroiditis. Vitamin D-treated women were also characterized by lower antibody titers and higher testosterone levels than the women receiving the remaining micronutrients. There were no differences in sexual functioning and depressive symptoms between the selenomethionine- and myo-inositol-treated women. The study results suggest that although all antibody-lowering treatments are associated with better sexual functioning and well-being in young women with euthyroid autoimmune thyroiditis, the greatest benefits are observed in patients receiving vitamin D. Full article

(This article belongs to the Special Issue Fat-Soluble Vitamins for Disease Prevention and Management)

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15 pages, 457 KiB

Open AccessArticle

Vitamin D Status Determines Cardiometabolic Effects of Cabergoline in Women with Elevated Prolactin Levels: A Pilot Study

by Robert Krysiak, Marcin Basiak, Grzegorz Machnik, Witold Szkróbka and Bogusław Okopień

Nutrients 2023, 15(10), 2303; https://doi.org/10.3390/nu15102303 - 14 May 2023

Cited by 6 | Viewed by 2957

Abstract

Both hyperprolactinemia and vitamin D deficiency appear to be associated with increased cardiometabolic risk. This study aimed to determine whether vitamin D status influences the cardiometabolic effects of cabergoline. The study included three matched groups of women with mild to moderate hyperprolactinemia: vitamin D-naive subjects with vitamin D insufficiency (group A), women with vitamin D deficiency/insufficiency successfully treated with vitamin D (group B), and vitamin D-naive individuals with normal vitamin D status (group C). Plasma prolactin, 25-hydroxyvitamin D, estradiol, glucose homeostasis markers, lipids, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and uric acid, as well as the urinary albumin-to-creatinine ratio (UACR), were measured at study entry and after four months of cabergoline treatment. Although cabergoline reduced prolactin levels and increased estradiol levels in all study groups, the effect on prolactin was more pronounced in groups B and C compared to group A. In groups B and C, the drug enhanced glucose homeostasis, increased HDL-cholesterol, and decreased triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR. In group A, only insulin resistance, hsCRP, and homocysteine were reduced by cabergoline. The effects on insulin sensitivity, HDL-cholesterol, triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR were proportional to the decrease in prolactin and baseline levels of 25-hydroxyvitamin D. The obtained results suggest that vitamin D status determines cabergoline’s cardiometabolic effects. Full article

(This article belongs to the Special Issue Fat-Soluble Vitamins for Disease Prevention and Management)

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11 pages, 909 KiB

Open AccessArticle

Serum 25-Hydroxyvitamin D Levels and Youth-Onset Type 2 Diabetes: A Two-Sample Mendelian Randomization Study

by Benjamin De La Barrera and Despoina Manousaki

Nutrients 2023, 15(4), 1016; https://doi.org/10.3390/nu15041016 - 17 Feb 2023

Cited by 5 | Viewed by 2641

Abstract

Observational studies have linked vitamin D insufficiency to pediatric type 2 diabetes (T2D), but evidence from vitamin D supplementation trials is sparse. Given the rising prevalence of pediatric T2D in all ethnicities, determining the protective role of vitamin D has significant public health importance. We tested whether serum 25-hydroxyvitamin D (25OHD) levels are causally linked to youth-onset T2D risk using Mendelian randomization (MR). We selected 54 single-nucleotide polymorphisms (SNPs) associated with 25OHD in a European genome-wide association study (GWAS) on 443,734 individuals and obtained their effects on pediatric T2D from the multi-ethnic PRODIGY GWAS (3006 cases/6061 controls). We applied inverse variance weighted (IVW) MR and a series of MR methods to control for pleiotropy. We undertook sensitivity analyses in ethnic sub-cohorts of PRODIGY, using SNPs in core vitamin D genes or ancestry-informed 25OHD SNPs. Multivariable MR accounted for the mediating effects of body mass index. We found that a standard deviation increase in 25OHD in the logarithmic scale did not affect youth-onset T2D risk (IVW MR odds ratio (OR) = 1.04, 95% CI = 0.96–1.13, p = 0.35) in the multi-ethnic analysis, and sensitivity, ancestry-specific and multivariable MR analyses showed consistent results. Our study had limited power to detect small/moderate effects of 25OHD (OR of pediatric T2D < 1.39 to 2.1). In conclusion, 25OHD levels are unlikely to have significant effects on the risk of youth-onset T2D across different ethnicities. Full article

(This article belongs to the Special Issue Fat-Soluble Vitamins for Disease Prevention and Management)

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14 pages, 771 KiB

Open AccessArticle

Improved HDL Cholesterol through Vitamin D Status Correction Substantially Lowers 10-Year Atherosclerotic Cardiovascular Disease Risk Score in Vitamin D-Deficient Arab Adults

by Shaun Sabico, Kaiser Wani, William B. Grant and Nasser M. Al-Daghri

Nutrients 2023, 15(3), 551; https://doi.org/10.3390/nu15030551 - 20 Jan 2023

Cited by 18 | Viewed by 4503

Abstract

This interventional study aimed to determine whether correcting vitamin D status in deficient Arab adults [25(OH)D <50 nmol/L] improves their 10-year risk of Atherosclerotic Cardiovascular Disease (ASCVD) risk scores. Saudi adults (58 males 62 females) with baseline vitamin D deficiency (<50 nmol/L) were given 50,000 IU cholecalciferol weekly for 2 months, then twice a month, followed by daily 1000 IU until month 6. Fasting blood samples were collected pre- and post-intervention and assessed for glucose, lipids, and 25(OH)D levels. The predicted 10-year ASCVD risk scores were calculated at baseline and after intervention. At baseline, significantly higher 10-year ASCDV risk scores were observed in males than females (9% vs. 3%, p < 0.001). After 6 months, only 21% (25 out of 120) achieved 25(OH)D levels above optimal level (≥75 nmol/L). While modest improvements were seen in glucose and lipid profiles, only HDL cholesterol showed favorable significant changes in all participants, which translated to significantly improved 10-year ASCVD risk scores independent of whether they achieved optimum vitamin D status. Still, those who achieved optimal vitamin D levels had a modestly larger decrease in ASCVD risk scores than those with less optimal 25(OH)D levels (−23% versus −18%) and this improvement was slightly more pronounced in males (−26% versus −10%, or 16% improvement) than females (−47% versus −32%, or 15% improvement). In conclusion, vitamin D status correction significantly enhances HDL cholesterol which prospectively reduces 10-year ASCVD risk as vitamin D levels approach optimum status among adult Arabs with baseline vitamin D deficiency. This improvement appears to be slightly more apparent in males than females. Full article

(This article belongs to the Special Issue Fat-Soluble Vitamins for Disease Prevention and Management)

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19 pages, 4936 KiB

Open AccessArticle

Vitamin A- and D-Deficient Diets Disrupt Intestinal Antimicrobial Peptide Defense Involving Wnt and STAT5 Signaling Pathways in Mice

by Louisa Filipe Rosa, Patricia P. Petersen, Lisa F. Görtz, Iris Stolzer, Valentina Kaden-Volynets, Claudia Günther and Stephan C. Bischoff

Nutrients 2023, 15(2), 376; https://doi.org/10.3390/nu15020376 - 11 Jan 2023

Cited by 7 | Viewed by 3317

Abstract

Vitamin A and D deficiencies are associated with immune modulatory effects and intestinal barrier impairment. However, the underlying mechanisms remain unclear. C57BL/6J mice were fed either a diet lacking in vitamin A (VAd), vitamin D (VDd) or a control diet (CD) for 12 weeks. Gut barrier function, antimicrobial peptide (AMP) defense and regulatory pathways were assessed. VAd mice compared to CD mice showed a reduced villus length in the ileum (p < 0.01) and decreased crypt depth in the colon (p < 0.05). In both VAd- and VDd-fed mice, ileal α-defensin 5 (p < 0.05/p < 0.0001 for VAd/VDd) and lysozyme protein levels (p < 0.001/p < 0.0001) were decreased. Moreover, mRNA expression of lysozyme (p < 0.05/p < 0.05) and total cryptdins (p < 0.001/p < 0.01) were reduced compared to controls. Furthermore, matrix metalloproteinase-7 (Mmp7) mRNA (p < 0.0001/p < 0.001) as well as components of the Wnt signaling pathway were decreased. VAd- and VDd-fed mice, compared to control mice, exhibited increased expression of pro-inflammatory markers and β-defensins in the colon. Organoid cell culture confirmed that vitamins A and D regulate AMP expression, likely through the Jak/STAT5 signaling pathway. In conclusion, our data show that vitamin A and D regulate intestinal antimicrobial peptide defense through Wnt and STAT5 signaling pathways. Full article

(This article belongs to the Special Issue Fat-Soluble Vitamins for Disease Prevention and Management)

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14 pages, 2155 KiB

Open AccessArticle

Fat-Soluble Vitamers: Parent-Child Concordance and Population Epidemiology in the Longitudinal Study of Australian Children

by Githal Randunu Porawakara Arachchige, Chris James Pook, Beatrix Jones, Margaret Coe, Richard Saffery, Melissa Wake, Eric Bruce Thorstensen, Justin Martin O’Sullivan and on behalf of the Child CheckPoint Team

Nutrients 2022, 14(23), 4990; https://doi.org/10.3390/nu14234990 - 24 Nov 2022

Viewed by 1803

Abstract

Fat-soluble vitamers (FSV) are a class of diverse organic substances important in a wide range of biological processes, including immune function, vision, bone health, and coagulation. Profiling FSV in parents and children enables insights into gene-environment contributions to their circulating levels, but no studies have reported on the population epidemiology of FSV in these groups as of yet. In this study, we report distributions of FSV, their parent-child concordance and variation by key characteristics for 2490 children (aged 11–12 years) and adults (aged 28–71 years) in the Child Health CheckPoint of the Longitudinal Study of Australian Children. Ten A, D, E and K vitamers were quantified using a novel automated LC-MS/MS method. All three K vitamers (i.e., K1, MK-4, MK-7) and 1-α-25(OH)₂D₃ were below the instrument detection limit and were removed from the present analysis. We observed a strong vitamer-specific parent-child concordance for the six quantifiable A, D and E FSVs. FSV concentrations all varied by age, BMI, and sex. We provide the first cross-sectional population values for multiple FSV. Future studies could examine relative genetic vs. environmental determinants of FSV, how FSV values change longitudinally, and how they contribute to future health and disease. Full article

(This article belongs to the Special Issue Fat-Soluble Vitamins for Disease Prevention and Management)

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16 pages, 1205 KiB

Open AccessReview

An Overview of Different Vitamin D Compounds in the Setting of Adiposity

by Eva E. Spyksma, Anastasia Alexandridou, Knut Mai, Dietrich A. Volmer and Caroline S. Stokes

Nutrients 2024, 16(2), 231; https://doi.org/10.3390/nu16020231 - 11 Jan 2024

Cited by 2 | Viewed by 2317

Abstract

A large body of research shows an association between higher body weight and low vitamin D status, as assessed using serum 25-hydroxyvitamin D concentrations. Vitamin D can be metabolised in adipose tissue and has been reported to influence gene expression and modulate inflammation and adipose tissue metabolism in vitro. However, the exact metabolism of vitamin D in adipose tissue is currently unknown. White adipose tissue expresses the vitamin D receptor and hydroxylase enzymes, substantially involved in vitamin D metabolism and efficacy. The distribution and concentrations of the generated vitamin D compounds in adipose tissue, however, are largely unknown. Closing this knowledge gap could help to understand whether the different vitamin D compounds have specific health effects in the setting of adiposity. This review summarises the current evidence for a role of vitamin D in adipose tissue and discusses options to accurately measure vitamin D compounds in adipose tissue using liquid chromatography tandem mass spectrometry (LC/MS-MS). Full article

(This article belongs to the Special Issue Fat-Soluble Vitamins for Disease Prevention and Management)

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14 pages, 673 KiB

Open AccessReview

Vitamin D and Its Association with H. pylori Prevalence and Eradication: A Comprehensive Review

by Maria Oana Săsăran, Cristina Oana Mărginean, Ancuta Lupu and Ana Maria Koller

Nutrients 2023, 15(16), 3549; https://doi.org/10.3390/nu15163549 - 11 Aug 2023

Cited by 1 | Viewed by 3019

Abstract

Taking into account previous data that sustain a relationship between vitamin D deficiency and higher H. pylori infection positivity rates, this review aims to assess the influence of vitamin D deficiency and/or insufficiency upon the prevalence of H. pylori infection and its eradication success. Three major databases were searched for articles that analyzed a relationship between vitamin D status and H. pylori infection. The literature search retrieved a total of 37 reports, after the article selection process. Hypovitaminosis D emerged as a potential risk factor for H. pylori infection, given the higher prevalence of vitamin D deficiency and/or insufficiency among H. pylori-positive subjects. Furthermore, the same type of micronutrient deficiency has been directly linked to H. pylori eradication failure. An inverse linear relationship between vitamin D status and gastric cancer risk exists, but the additional involvement of H. pylori in this correlation is still in question. The potential benefit of oral supplements in enhancing the success of classical therapeutic regimens of H. pylori still requires future research. Future population-based studies from larger geographical areas are warranted to address this subject in more depth. Full article

(This article belongs to the Special Issue Fat-Soluble Vitamins for Disease Prevention and Management)

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37 pages, 2062 KiB

Open AccessReview

Vitamin K and the Visual System—A Narrative Review

by Michael A. Mong

Nutrients 2023, 15(8), 1948; https://doi.org/10.3390/nu15081948 - 18 Apr 2023

Viewed by 5783

Abstract

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting, however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic-related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in mice. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with those with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is, therefore, the intention of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and provide some historical context for recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon in the hope of raising awareness and encouraging continued VK-related investigations in this important and highly specialized sensory system. Full article

(This article belongs to the Special Issue Fat-Soluble Vitamins for Disease Prevention and Management)

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