Vitamin D does not reduce cancer or cardiovascular events in healthy adults, trial findsBMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k4776 (Published 12 November 2018) Cite this as: BMJ 2018;363:k4776
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Fatal myocardial infarctions reduced Re: Vitamin D does not reduce cancer or cardiovascular events in healthy adults, trial finds
Susan Mayor’s Research News reports that a large randomised trial has found no benefits from omega 3 fatty acids in primary prevention cardiovascular events in healthy people over 50. JoAnn Manson and the Vital Research Group’s trial enrolled 25,871 men and women. Those randomised to take one daily fish oil capsule had significantly fewer myocardial infarctions but the strange conclusion was no reduction in major cardiovascular events.1
The total risk of myocardial infarction was reduced significantly, 0.72 (95% CI, 0.59 to 0.90); total coronary heart disease (hazard ratio, 0.83; 95% CI, 0.71 to 0.97), percutaneous intervention PCI (hazard ratio, 0.78; 95% CI, 0.63 to 0.95), and fatal myocardial infarction were reduced by half (hazard ratio, 0.50; 95% CI, 0.26 to 0.97).
One fish-oil capsule contained 840 mg of n-3 fatty acids, including 460 mg of eicosapentaenoic acid [EPA] and 380 mg of docosahexaenoic acid [DHA]) which is equivalent to one and a half fish meals a week. Fish has long been known as a brain food and these are remarkably excellent results for such a small daily amount.
Edward N Seguel, who developed the laboratory analysis of fatty acids in blood and fat, wrote that there has been reluctance to believe there can be deficiencies in omega-6 as well as omega-3 essential fatty acids. Perhaps this is because measuring cholesterol is routine but red cell fatty essential fatty acid (EFA) levels are not usually measured. He warned that researchers can be like blind men touching different parts of an elephant (and not knowing it). Every experiment is a tiny surface in the multidimensional space of variables and chemicals in the body.2
In my experience, three fish oil capsules and/or three evening primrose oil capsules were often needed for repletion before conception. High doses of n-3 oils taken alone can cause deficiencies of n-6 fatty acids and vice versa. It is also important to replete mineral and vitamin deficiencies, especially in women who have been taking exogenous progestogens and/or oestrogens. Both the n-3 and n-6 elongation pathways need the activities of the enzymes delta-6 desaturase, elongases or 5 desaturase which are adversely affected by deficiencies of co-factors zinc, magnesium and copper, and are also adversely affected by steroids and aspirin (NSAIDs). Most women seeking preconception care can seem apparently healthy but have histories of unexplained infertility, miscarriages and past use of steroidal hormonal contraceptives. They commonly have numerous mineral and vitamin deficiencies. Dr John McLaren-Howard measured red blood cell EFA profiles and we found a higher percentage of women with both n-3 and n-6 pathway blocks between 1990 and 2005. Most women tested had used either contraceptive or menopausal hormonal steroids. Increases in the number of women of childbearing age with EFA deficiencies is alarming.3,4
1 Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Albert CM, Gordon D, Copeland T, D'Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, Buring JE; VITAL Research Group. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med. 2018 Nov 10. doi: 10.1056/NEJMoa1811403. [Epub ahead of print]
2 Siguel E. Measuring Fatty Acids, http://bmj.com/cgi/eletters/330/7498/991#107906, 25 May 2005
3 Grant ECG. Re: Measuring Fatty Acids - Possible increases in omega-3 and omega-6 deficiencies among women. Rapid Response10 June 2005 https://www.bmj.com/rapid-response/2011/10/30/re-omega-6-and-omega-3-puf...
4 Grant EC, Importance of omega-3 and omega-6 PUFA deficiencies Re: Dyslipidaemia and cardiovascular risk https://www.bmj.com/content/360/bmj.k835/rr-0
Importance of omega-3 and omega-6 PUFA deficiencies Re: Dyslipidaemia and cardiovascular risk
Competing interests: No competing interests
But vitamin D reduces cancer and cancer mortality in deficient adults
The crucial point of the vitamin D discussion is: What level of serum 25(OH)D do we call sufficient or healthy? Is it 25, 50 or 75 nmol/l? If we want to evaluate whether taking vitamin D and repleting serum levels to normal is beneficial, then we must first define "deficiency", then take deficient individuals and conduct a trial giving a sufficient amount of supplement to one group or placebo to the other group. Most vitamin D researchers define the cut off for sufficiency as 50 to 75 nmol/l, not any longer 25 nmol/l (as SACN still does (1)).
In VITAL (2) most participant of both groups were not vitamin D deficient (assuming 50 nmol/l as sufficiency), because all participants lived in the US, where the average 25(OH)D level is around 50 nmol/l and most participants were therefore replete (US has widespread fortification). It meant results are not as clear cut as they could have been, they were "noisy results”.
In contrast, in the UK average serum 25(OH)D levels are lower than in the US (1) and a similar trial conducted in the UK might have produced more positive headlines.
But despite the negative headlines, in VITAL slim people, BMI < 25, did have less invasive cancers, hazard ratio 0.76 (0.63–0.90), with vitamin D supplements. More obese people might have needed a higher dose of vitamin D, as the authors also discussed.
In addition, death from all cancers was significantly lower with vitamin D than with placebo , in a secondary analysis, hazard ratio, 0.75 [95% CI, 0.59 to 0.96].
As GP I observed in the last 10 years that vitamin D supplementation for our cancer patients had clearly beneficial effects including surprisingly long survival in individual cases.
I feel it cannot be concluded from VITAL that vitamin D does not play a role in reducing cancer incidence or cancer mortality in vitamin D deficient individuals. This could particularly be important in the UK with her lower serum 25(OH)D levels.
(1) SACN 2016 Vitamin D and health. https://www.gov.uk/government/groups/scientific-advisory-committee-on-nu...
(2) Manson JE, Cook NR, Lee IM, et al. VITAL Research group. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. November 10, 2018, at NEJM.org.
Competing interests: No competing interests