Coronary artery calcification (CAC) and especially progression in CAC is a strong predictor of acute myocardial infarction and cardiovascular mortality. Supplementation with vitamin K2 and D3 has been suggested to have a protective role in the progression of CAC. In this study, we will examine the effect of vitamins K2 and D3 in men and women with severe CAC. We hypothesise that supplementation with vitamins K2 and D3 will slow down the calcification process.
Method and analysis
In this multicentre and double-blinded placebo-controlled study, 400 men and women with CAC score≥400 are randomised (1:1) to treatment with vitamin K2 (720 µg/day) and vitamin D3 (25 µg/day) or placebo treatment (no active treatment) for 2 years. Among exclusion criteria are treatment with vitamin K antagonist, coagulation disorders and prior coronary artery disease. To evaluate progression in coronary plaque, a cardiac CT-scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is progression in CAC score from baseline to follow-up at 2 years. Among secondary outcomes are coronary plaque composition and cardiac events. Intention-to-treat principle is used for all analyses.
Ethics and dissemination
There are so far no reported adverse effects associated with the use of vitamin K2. The protocol was approved by the Regional Scientific Ethical Committee for Southern Denmark and the Data Protection Agency. It will be conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported.
Hasific S, Øvrehus KA, Hosbond S, Lambrechtsen J, Kumarathurai P, Mejldal A, Ravn EJ, Rasmussen LM, Gerke O, Mickley H, Diederichsen A. Effects of vitamins K2 and D3 supplementation in patients with severe coronary artery calcification: a study protocol for a randomised controlled trial. BMJ Open. 2023 Jul 14;13(7):e073233. doi: 10.1136/bmjopen-2023-073233. PMID: 37451735; PMCID: PMC10351276.
In recent years, clinical trials increasingly have given large doses of vitamin D supplements to investigate possible health benefits beyond bone at high 25-hydroxyvitamin D levels. However, there are few publications on the safety of high-dose vitamin D given long term. The study objective was to investigate the cumulative relative risk (RR) of total adverse events, kidney stones, hypercalcemia and hypercalciuria from ≥2800 IU/d vitamin D2 or D3 supplementation, followed for one year or more in randomized controlled trials (RCTs). A systematic review was conducted in Medline Ovid, EMBASE and Cochrane in March 2018 to update results of studies published since a previous review in October 2015. RCTs were included if they gave vitamin D2 or D3 at ≥2800 IU/d for at least one year and reported on total adverse events or at least one calcium-related adverse event. There were a total of 32 studies that met the inclusion criteria. Of these, only 15 studies (3150 participants) reported one or more event of the outcomes of interest. Long-term high-dose vitamin D supplementation did not increase total adverse events compared to placebo in 1731 participants from 10 studies (RR = 1.05; 95% CI = 0.88, 1.24; p = 0.61), nor kidney stones in 1336 participants from 5 studies (RR = 1.26; 95% CI = 0.35, 4.58; p = 0.72). However, there was a trend for vitamin D to increase risk of hypercalcemia in 2598 participants from 10 studies (RR = 1.93; 95% CI = 1.00, 3.73; p = 0.05); while its effect on hypercalciuria in only 276 participants from 3 studies was inconclusive (RR = 1.93; 95% CI = 0.83, 4.46; p = 0.12). In conclusion, one year or longer supplementation with a large daily, weekly or monthly dose of vitamin D2 /D3 did not significantly increase a risk of total adverse events or kidney stones, although there was a trend towards increased hypercalcemia, and possibly for hypercalciuria.
Malihi Z, Wu Z, Lawes CMM, Scragg R. Adverse events from large dose vitamin D supplementation taken for one year or longer. J Steroid Biochem Mol Biol. 2019 Apr;188:29-37. doi: 10.1016/j.jsbmb.2018.12.002. Epub 2018 Dec 6. PMID: 30529281.
Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial
Abstract
ObjectiveTo investigate whether supplementing older adults with monthly doses of vitamin D alters the incidence of major cardiovascular events.
DesignRandomised, double blind, placebo controlled trial of monthly vitamin D (the D-Health Trial). Computer generated permuted block randomisation was used to allocate treatments.
SettingAustralia from 2014 to 2020.
Participants21 315 participants aged 60-84 years at enrolment. Exclusion criteria were self-reported hypercalcaemia, hyperparathyroidism, kidney stones, osteomalacia, sarcoidosis, taking >500 IU/day supplemental vitamin D, or unable to give consent because of language or cognitive impairment.
Intervention60 000 IU/month vitamin D3(n=10 662) or placebo (n=10 653) taken orally for up to five years. 16 882 participants completed the intervention period: placebo 8270 (77.6%); vitamin D 8552 (80.2%).
Main outcome measuresThe main outcome for this analysis was the occurrence of a major cardiovascular event, including myocardial infarction, stroke, and coronary revascularisation, determined through linkage with administrative datasets. Each event was analysed separately as secondary outcomes. Flexible parametric survival models were used to estimate hazard ratios and 95% confidence intervals.
Results21 302 people were included in the analysis. The median intervention period was five years. 1336 participants experienced a major cardiovascular event (placebo 699 (6.6%); vitamin D 637 (6.0%)). The rate of major cardiovascular events was lower in the vitamin D group than in the placebo group (hazard ratio 0.91, 95% confidence interval 0.81 to 1.01), especially among those who were taking cardiovascular drugs at baseline (0.84, 0.74 to 0.97; P for interaction=0.12), although the P value for interaction was not significant (<0.05). Overall, the difference in standardised cause specific cumulative incidence at five years was −5.8 events per 1000 participants (95% confidence interval −12.2 to 0.5 per 1000 participants), resulting in a number needed to treat to avoid one major cardiovascular event of 172. The rate of myocardial infarction (hazard ratio 0.81, 95% confidence interval 0.67 to 0.98) and coronary revascularisation (0.89, 0.78 to 1.01) was lower in the vitamin D group, but there was no difference in the rate of stroke (0.99, 0.80 to 1.23).
ConclusionsVitamin D supplementation might reduce the incidence of major cardiovascular events, although the absolute risk difference was small and the confidence interval was consistent with a null finding. These findings could prompt further evaluation of the role of vitamin D supplementation, particularly in people taking drugs for prevention or treatment of cardiovascular disease.
Trial registrationACTRN12613000743763
ThompsonB,WaterhouseM,EnglishD R,McLeodD S,ArmstrongB K,BaxterCet al.Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trialBMJ2023;381:e075230doi:10.1136/bmj-2023-075230
Both vitamin D insufficiency and deficiency are now well-documented worldwide in relation to human health, and this has raised interest in vitamin D research. The aim of this article is therefore to review the literature on sources of vitamin D. It can be endogenously synthesised under ultraviolet B radiation in the skin, or ingested through dietary supplements and dietary sources, which include food of animal and plant origin, as well as fortified foods. Vitamin D is mainly found in two forms, D3 (cholecalciferol) and D2 (ergocalciferol). In addition to the D3 and D2 forms of vitamin D, 25-hydroxy vitamin D also contributes significantly to dietary vitamin D intake. It is found in many animal-derived products. Fortified food can contain D3 or D2 forms or vitamin D metabolite 25-hydroxy vitamin D. Not many foods are a rich source (> 4 μg/100 g) of vitamin D (D represents D3 and/or D2), e.g., many but not all fish (5-25 μg/100 g), mushrooms (21.1-58.7 μg/100 g), Reindeer lichen (87 μg/100 g) and fish liver oils (250 μg/100 g). Other dietary sources are cheese, beef liver and eggs (1.3-2.9 μg/100 g), dark chocolate (4 μg/100 g), as well as fortified foods (milk, yoghurt, fat spreads, orange juice, breakfast grains, plant-based beverages). Since an adequate intake of vitamin D (15 μg/day set by the European Food Safety Authority) is hard to achieve through diet alone, dietary supplements of vitamin D are usually recommended. This review summarizes current knowledge about different sources of vitamin D for humans.
Benedik E. Sources of vitamin D for humans. Int J Vitam Nutr Res. 2022 Mar;92(2):118-125. doi: 10.1024/0300-9831/a000733. Epub 2021 Oct 18. PMID: 34658250.
The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in cosmetic products. The widespread human exposure and its potential toxic and carcinogenic activities raise safety concerns. Chemical analysis reveals that the Aloe plant contains various polysaccharides and phenolic chemicals, notably anthraquinones. Ingestion of Aloe preparations is associated with diarrhea, hypokalemia, pseudomelanosis coli, kidney failure, as well as phototoxicity and hypersensitive reactions. Recently, Aloe vera whole leaf extract showed clear evidence of carcinogenic activity in rats, and was classified by the International Agency for Research on Cancer as a possible human carcinogen (Group 2B). This review presents updated information on the toxicological effects, including the cytotoxicity, genotoxicity, carcinogenicity, and adverse clinical effects of Aloe vera whole leaf extract, gel, and latex.
Guo X, Mei N. Aloe vera: A review of toxicity and adverse clinical effects. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2016 Apr 2;34(2):77-96. doi: 10.1080/10590501.2016.1166826. PMID: 26986231; PMCID: PMC6349368.
Kamla Kant Shukla 1, Abbas Ali Mahdi, Mohammad Kaleem Ahmad, Shyam Pyari Jaiswar, Satya Narain Shankwar, Sarvada Chandra Tiwari
The goal of this study was to see how Mucuna pruriens affected infertile males who were under psychological stress. A questionnaire and increased blood cortisol levels were used to examine 60 patients who were having infertility screening and were found to be suffering from psychological stress. As controls, 60 age-matched healthy males with normal sperm parameters who had previously started at least one pregnancy were included. Subjects who were under psychological stress had lower sperm count and motility, according to the findings. M. pruriens treatment reduced psychological stress and reduced seminal plasma lipid peroxide levels, as well as improving sperm count and motility. It may be inferred that M. pruriens not only reactivates infertile men’s antioxidant defense system, but also aids in stress management and increases sperm quality.
