This randomized, double-blind, placebo-controlled trial investigated whether supplementing older adults with monthly doses of vitamin D alters the incidence of major cardiovascular events.
A total of 21 315 participants aged 60-84 years were enrolled. Exclusion criteria were self-reported hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia, sarcoidosis, taking >500 IU/day supplemental vitamin D, or being unable to give consent because of language or cognitive impairment.
The trial participants received 60 000 IU/month of 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%). The 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 analyzed separately as secondary outcome. Flexible parametric survival models were used to estimate hazard ratios and 95% confidence intervals.
21 302 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 standardized 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). The incidence of adverse events was similar in the two groups.
The authors concluded that vitamin D supplementation might reduce the incidence of major cardiovascular events, particularly myocardial infarction and coronary revascularisation. This protective effect could be more marked in those taking statins or other cardiovascular drugs at baseline. Subgroup analyses in other large trials might help to clarify this issue. In the meantime, these findings suggest that conclusions that vitamin D supplementation does not alter risk of cardiovascular disease are premature.
This is an impressive study and a disappointing result. That vitamin D supplementation might reduce the incidence of major cardiovascular events was known before; thus we would not have needed such an expensive study to arrive at this conclusion. That the protective effect might be more marked in patients taking statins or other cardiovascular drugs seems odd, in my view. Could it be, I ask myself, that the protective effect is unrelated to cardiovascular drugs but simply more marked in those individuals who are at a higher than average risk of cardiovascular events?
In any case, the protective effect is small and seems to be of questionable clinical relevance.
15 Responses to Does Vitamin D reduce the incidence of major cardiovascular events?
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Correct me if I’m wrong, but what I’m missing in this study is the actual prevalence of vitamin D deficiency among the studied population. I see it mentioned one or two times, but only as ‘expected deficient’, without any measurements or conclusions.
I think that this is a bit of a shame, because giving vitamin D supplements to non-deficient people is not very likely to produce significant results. This is also a missed chance because older people (the studied groups) tend to have vitamin D deficiency more often than younger people, but that this also depends heavily on lifestyle and nutritional habits.
The reason for bringing this up is that more severe vitamin D deficiency can cause hypocalcemia, which in turn can cause cardiac arrhythmia. Also, lots of conditions including infections (such as Covid-19(*)) and cancer can cause vitamin D deficiency – and in these cases, supplementation can improve health.
*: It is of course not the other way round, so no, contrary to what Covid ‘sceptics’ claim, vitamin D is not a cure for Covid.
I have been wondering about that too.
If I see it correctly, these were well-fed Australians and thus not deficient; the trial was aimed at evaluating, if in such a population D supplements have an effect.
While vitamin D might not be a cure for covid. I’ll go out on a limb and say it’s a good preventative measure for covid.
@Pete Frampton
I will go out on all four limbs and say that Vitamin D cannot prevent COVID.
@Pete Frampton
Alas, no: https://jamanetwork.com/journals/jama/fullarticle/2797574
Ahhhh, could Vitamin D be a cure-all? These studies & meta analyses are usually flawed, because they use a standard ‘dose’ of a specific nutrient (sounds like SCAM in disguise Edzard?) to discover if an isolated nutrient can produce statistically significant results – in this case to reduce the incidence of ‘major cardiovascular events’.
Vitamin D is NOT a synthetic drug or medical treatment. In order for a person to gain optimum benefit from skin exposure to direct sunlight, from food (usually minimal) or from Vitamin D3 supplements (pill or Liposomal), an individual has to convert Vitamin D via the liver and kidneys into the active form which is …. Calcitriol!
The effective conversion from Vitamin D to Calcitriol inside the body can vary considerably from person to person. It is generally accepted – even by some physicians – that a serum 25(OH)D test provides a useful indication of how effectively a subject is producing the active form of Vitamin D in their body.
However, there are a number of co-factors which this study and others never include with Vitamin D, they are magnesium, selenium, phosphorous and vitamin K2 (MK-7) to name just a few.
@Mike Grant
Nope. There is no such thing as a ‘cure-all’, or a ‘superfood’. There are literally thousands of chemicals we need in the right amounts or proportions to stay alive and healthy. Most of which we can make ourselves, and some of which we get with our food or in the form of supplements. But none of those chemicals does anything special for our health in higher than normal doses or in highly specific combinations.
This is just an argument to support the false claim that vitamin D is a kind of panacea after all, much like the false claim that hydroxychloroquine absolutely helps with Covid-19, but that researchers all failed to combine it with other stuff (usually zinc is mentioned).
Why this is a false claim? Simple: virtually everyone has high enough levels of those micronutrients in their body already, and even people who routinely take extra doses of those micronutrients (usually in combination with vitamin D and other vitamins) do not enjoy a spectacularly better health than other people who don’t take those supplement cocktails. For most people, supplements are simply a waste of money. Things like sufficient exercise and avoiding junkfood are things that really help us stay healthy, not ‘superfoods’ or supplements. But even the healthiest lifestyle is no absolute guarantee for a disease-free life. Sometimes bad sh*t just happens.
Surge In Type 1 Diabetes BBC Report:
https://www.bbc.co.uk/news/health-66054946
Quote from study (link below):
“Vitamin D deficiency has been linked to the onset of diabetes …
Vitamin D deficiency contributes to both the initial insulin resistance and the subsequent onset of diabetes caused by β-cell death. Vitamin D acts to reduce inflammation, which is a major process in inducing insulin resistance ….. A relationship between type 1 diabetes mellitus and vitamin D deficiency has been reported. The prevalence of vitamin D deficiency in patients with type 1 diabetes was 15% to 90.6%”.
https://pubmed.ncbi.nlm.nih.gov/28341729/
My comment: Governments and some assorted medics refuse to acknowledge the importance of Vitamin D (the active form being Calcitriol) to humans. The trials and studies using Vitamin D as an isolated drug are misleading and ignorant. As usual, it’s about LEVELS (in the blood) and not one-size-fits-all DOSAGE!
“Governments and some assorted medics refuse to acknowledge the importance of Vitamin D (the active form being Calcitriol) to humans.”
No! It’s called VITAmine because we all know it’s VITAl!
“Overall, the difference in standardized 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.”
If I understand that correctly…
number needed to treat (NNT) = 1/(Iu − Ie), where
• Iu is the incidence in the control (unexposed) group;
• Ie is the incidence in the treated (exposed) group,
So, Ie is 5.8 events per 1000 participants less than Iu,
therefore NNT = 1/( 5.8/1000 ) ≈ 172 as stated.
However, using their 95% confidence interval (−12.2 to 0.5 per 1000 participants):
NNT lies in the ranges +82..+infinity, and −2000..−infinity.
https://en.m.wikipedia.org/wiki/Number_needed_to_treat
yes, I think that’s right
To Richard Rasker
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521296/
While not evidence, it makes a strong correlation between sunlight and covid cases and covid severity. What we DON”T know about the RCT’s mentioned is, if test patients were/were not given any fat combined with the vitamin D supplement, as fat is required to absorb a fat-soluble supplement. This is one such reason I don’t always believe results of such trials, the design parameters may have been flawed.
“it has been observed that the COVID‐19 cases are much lower and less severe in countries closer to the equator than those farther away from the equator; likely due to increased sun exposure, which is the natural source of vitamin D. 17 Furthermore, clinical studies by Meltzer et al. 21 have shown that the relative risk of COVID‐19 infection nearly doubles for patients with vitamin D deficiency. Because of these inconsistent reports, it seems critical to understand the role of vitamin D at the molecular level, especially in the context of COVID‐19 infection. As the binding of the viral protein with the host cell receptor depends on the thiol‐disulfide balance,”
In spite of the fore mentioned potential shortfall in this specific RCT, the study reveals some interesting facts to be known.
“Studies were performed where cohorts of patients with HIV had their vitamin D levels monitored in addition to infection progression. It was found that those with lower baseline vitamin D levels experienced faster disease progression. 44 , 45 Another study found that children with high vitamin D levels were less likely to contract influenza. 46 In the case of Hepatitis C, it was also found that vitamin D supplementation improved the body’s response to the virus. Low levels of vitamin D were correlated with a reduced sustained viral response in patients with Hepatitis C. 47 , 48 , 49 In regard to RSV and dengue virus, multiple studies were performed to investigate the role vitamin D plays in disease progression. A mutation in VDR is correlated to more severe disease progression in RSV patients. 50 , 51 Also, treatment of Dengue‐infected monocytic U937 cells with vitamin D resulted in a significant reduction in the number of infected cells; vitamin D also lowered the levels of proinflammatory cytokines. 52 In a separate study, VDR agonists were found to have antiviral activities. 53 It has also been reported that vitamin D has a preventive effect on SARS‐CoV‐2 viral infection, which causes immune activation and systemic hyperinflammation.”
@Pete Frampton
My dear chap, are you implying that you don’t trust RCTs because the methodology MAY BE flawed but you will blindly believe hypotheses presented in a review article that supports your preconceived notions of what Vitamin D can and cannot do?
Have you read the RCT Richard linked to before deciding that RCT methodologies tend to be flawed? If you had bothered to, you would have found out that majority of participants in the trial https://www.bmj.com/content/378/bmj-2022-071230 were given this supplement: https://www.pharmanord.com/us-products/bio-vitamin-d3-125mg
Bolding mine.
Perhaps you should make an effort to read the methodology of the RCT before critiquing it.
Talker
Ohh… I read Richard’s links, yes.
The link you provided is a completely different from his links.
LOL @Pete Frampton a.k.a RG
Reading is not your strong suite and everyone here is aware of that. Hiding behind a different moniker wont make it any different.