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Vitamin D, fish oil fall short in CVD, cancer prevention

Audrey Abella
16 Nov 2018
Dr JoAnn Manson discusses the principal results of the VITAL trial.

Supplementation with either omega-3 fatty acids (ie, fish oil) or vitamin D did not reduce the incidence of major cardiovascular (CV) events (ie, composite of myocardial infarction [MI], stroke, and CV death) or total invasive cancer, according to the VITAL* trial presented at AHA 2018.

In this primary-prevention trial, 25,871 healthy adults (mean age 67 years, 51 percent female) were randomized 1:1 to receive 2,000 IU/day of vitamin D or placebo. Participants were further randomized 1:1 to receive 1 g/day of fish oil (EPA** 460 mg + DHA*** 380 mg [1.3:1]) or placebo. Median follow-up was 5.3 years. [AHA 2018, abstract 19539; N Engl J Med 2018;doi:10.1056/NEJMoa1809944; N Engl J Med 2018;doi:10.1056/NEJMoa1811403]

A similar number of major CV events was reported in both vitamin D and control arms, implying that vitamin D did not reduce CV outcomes compared with placebo (n=396 vs 409, hazard ratio [HR], 0.97; p=0.69). There was also no cancer benefit with vitamin D vs placebo (n=793 vs 824, HR, 0.96; p=0.47).

Omega-3 was similarly unhelpful in reducing both CV (n=386 vs 419, HR, 0.92; p=0.24) and cancer events (n=820 vs 797, HR, 1.03; p=0.56) compared with placebo.

Despite these findings, there were no significant side effects (eg, bleeding, hypercalcaemia, or gastrointestinal symptoms) with either vitamin D or omega-3 nor did they have any synergistic effect, noted the researchers.

 

Subgroup findings shed some hope

Of note however were the reductions in total MI rates with omega-3 after excluding the first 2 years of follow-up (HR, 0.72; pnominal<0.05), as well as in omega-3 recipients with low dietary fish consumption (<median 1.5 servings/week, HR, 0.60).

Total MI rates were also reduced among African-Americans receiving omega-3 (HR, 0.23), suggesting that omega-3 has a greater CV benefit in this ethnic group than in others, noted the researchers. “If this finding is confirmed and replicated, it may point to a very promising approach to reducing coronary risk among African-Americans,” said study author Dr JoAnn Manson from the Department of Medicine of Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts, US, in a press release. Nonetheless, this merits further investigation as this might have been a “chance finding” given the similar blood levels of EPA and DHA among African-Americans and non-Hispanic whites, added the researchers.

Regarding cancer events, there was a reduction in cancer deaths with vitamin D vs placebo after excluding early follow-up (HR, 0.75; pnominal=0.024). Despite data supporting the mechanisms by which vitamin D may inhibit carcinogenesis and tumour progression, [Nat Rev Cancer 2014;14:342-357] the long latency for cancer development warrants an extended follow-up to capture latency effects and further establish the potential effects of vitamin D on cancer, noted the researchers.

 

Dose-response relationship

Although the researchers used the AHA-recommended omega-3 dose for cardioprotection, dose-response relationships were not explored, noted the researchers. [Circulation 2018;138:e35-e47; Circulation 2017;135:e867-e884]

With regard to vitamin D, extremely low levels might signify stronger effects on risk, noted the researchers. “However, maintaining participants in a vitamin D-deficient state and circumventing real-world clinical care for 5 years would be neither ethical nor feasible.”

Further trials are thus warranted not only to evaluate dose-response relationships but also to establish the benefits and risks of taking omega-3 and vitamin D supplements, said the researchers. Ancillary studies evaluating other outcomes (ie, diabetes, atrial fibrillation, cognition, autoimmune disorders) are in progress, they added.

Pending further outcomes, there’s no reason to discontinue if individuals are already on omega-3 and/or vitamin D, while those considering taking these supplements are advised to discuss their options with their healthcare providers, noted Manson. “[Moreover,] medical and public health authorities may [refer to] the study results and decide if clinical guidelines should be updated,” she added.

However, Dr Kim Eagle from the University of Michigan in Ann Arbor, Michigan, US commented that the findings “probably put to rest the question of whether all people should be taking [fish oil]”. “[While] certain patients may benefit from vitamin D … it does not appear to have benefit [for primary prevention of heart disease],” he added.

 

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Most Read Articles
Elvira Manzano, 22 Jan 2018
A new study has shown an independent association between periodontal disease and incident stroke risk. What’s interesting is routine dental care can attenuate the stroke risk.
Audrey Abella, 17 Dec 2018
Low rates of cardiovascular (CV) or major bleeding complications were observed among octogenarians who were receiving active NOAC* therapy, suggesting that long-term anticoagulation with NOACs may result in a good risk-benefit ratio in this patient subgroup, according to data presented at ASH 2018.
Pank Jit Sin, 01 Feb 2019
Single pill combination (SPC) therapy is increasingly accepted and helps to overcome some of the problems associated with multipharmacy and compliance, says an expert. 
08 Mar 2019
Individuals who get fewer hours of sleep per night are more likely to have or develop atrial fibrillation, a recent study suggests.