Several observational studies have shown eating more fruit and vegetables helps to reduce several chronic illnesses including heart disease and cancer. As such it has been thought this may be due to the multi-vitamins and oxidants present within those fruit and vegetables that may cause this effect. Further observational studies have looked at supplements with promising links however this may well be due to other factors such as those who take supplements may make other health and lifestyle choices. Hence randomized controlled trials (RCTs) are a better study design to determine whether supplements of multi-vitamins and oxidants might affect disease risk. In animals studies and on human cells tissues supplements of antioxidants have shown beneficial effects but again this does not necessarily translate into an overall beneficial effect when taken in real life as discussed elsewhere. Many of the human RCTs have been too small scale and therefore under-powered to show a statistically significant effect or the effect has been conflicting thus a pooling of these results through meta-analyses has been conducted by a few researchers which we will explore.
All-Cause Death Rates – Mortality
In a meta-analysis of 47 high quality (low bias) randomised control trials (RCTs) involving over 180,000 participants by Bjelakovic et al reported in 2007 that vitamin A, vitamin E and beta-carotene supplements were all individually associated with increased death rate. Vitamin C and selenium supplements were not associated with death.
The same group updated their review in 2012 to include 56 RCTs with over 244,000 participants and found similar results in high quality trials with low risk of bias. The break down is as follows;
- Vitamin C & Selenium did not significantly affect mortality.
- Vitamin A, Vitamin E & Beta-carotene all significantly increased mortality.
This is clearly a worrisome trend, that supplements with Vitamin A, Vitamin E and Beta-carotene all increase the risk of all-cause death. Many hypotheses have been put forward to try and explain this effect.
Chowdary et al have found some survival benefit with Vitamin D3 but not Vitamin D2 however many of the studies were high risk of bias and the remaining studies had participants that were mainly an elderly population. Another trial called VITAL is under way and is expected to report next year.
In a meta-analysis of 22 RCTs involving over 160,000 participants by Myung et al reported in 2010, that antioxidant supplements had no primary or secondary preventive effects on cancer and even increased the risk of bladder cancer. Overall, none of the antioxidant supplements had any significant influence on cancer prevention irrespective of whether;
- Primary prevention trials – those without current or previous cancer
- Secondary prevention trials – those with current or previous cancer.
- Type of antioxidant administered singly
- Vitamin A,
- Vitamin, &
The increased risk of bladder cancer was seen mainly in those who already had current or previous cancer (secondary prevention) and the effect in those without previous cancer needs to be studied further before making conclusions in that group (primary prevention).
Vitamin C supplementation was also studied but not singly as it was only given in combination with other antioxidants and so falls under the general overall prevention statistics of having no effect. In the previous section vitamin C supplements did not affect all-cause death (mortality). I want to digress a little here and discus an issue related to Vitamin C and cancer.
Linus Pauling (died 1994) was well-known for his two Nobel prizes in the field of chemistry and with this ‘celebrity status’ went on to advocate Vitamin C supplements for treatment of cancer patients based upon his own poor quality evidence. The Mayo clinic went on to test this hypothesis with three separate rigorous studies each time showing no effect. Pauling then changed stratergy by advocating synthetic intravenous vitamin C infusions provided by the pharmaceutical industry again without any substantiated proof. It is possible that such a treatment may work but the point however is that there was no good quality evidence for it and advocating it as a cure was out right quackery. As such, it should only be used in the process of a clinical trial to determine its effectiveness. The Linus Pauling Institute openly declared in 2004 that the claimed cure by Pauling himself was purely a “theoretical” one without any evidence backing it up.
Despite this, I remember in 2009 when the healthymuslim establishment arose and several community leaders who are untrained in health, nutrition or medicine but have some training in chemistry and biochemistry went onto advocate to individual community members whose relatives were suffering from cancer that they should be treated with Intravenous Vitamin C infusions at expensive private clinics and that they needed to avoid conventional treatment (provided free of charge by state funding). Conventional treatment does have a good evidence base and no doubt this has led to earlier death through that bad advice.
This reminds us of the man in the Prophetic narrations who had a head injury and was incorrectly advised to take a bath and subsequently died as a result. It is this health tribulations that we are trying to address on this site. We will discuss the issue of the other flimsy evidence based treatments that are being advocated soon, inshallah.
Cardiovascular Disease – Heart disease & Strokes
Cardiovascular disease remains the leading cause of death and disability world-wide thus its study is an important health aspect. A meta-analysis of 50 randomised controlled trials involving over 290,000 participants also by Myung et al in 2012 reported the effects of vitamins and antioxidant supplements on cardiovascular disease (30 in primary prevention, 5 industry sponsored) and involved Vitamins A, B6 , B12 , C, D & E, beta-carotene, folic acid and selenium.
They found no reduction in the risk of major cardiovascular events such as heart attacks or stroke. A detailed sub-analysis found that overall there was no beneficial effect irrespective of the;
- type of prevention,
- type of vitamins and antioxidants,
- type of cardiovascular outcomes,
- study design,
- methodological quality, ( high or low quality)
- duration of treatment,
- funding source (pharmaceutical industry or community funded),
- provider of supplements,
- type of control,
- number of participants in each trial, and
- supplements were given singly or in combination with other supplements.
Among the subgroup analyses by the type of cardiovascular outcomes;
- Vitamin B6 was associated with a decreased risk of cardiovascular death in high quality trials, and
- Vitamin E supplementation with a reduced risk of heart attacks.
However these beneficial effects were seen only in trials in which the supplements were supplied by the pharmaceutical industry which is always a little suspect as the findings are not reproduced in the community-funded trials.
Eye Disease – Age-Related Macular Degeneration
I have included this for completion as it is a well conducted trial and falls out with the previous sections. A randomised control trial called the Age-Related Eye Disease Study investigated 3,460 participants with varying degrees of age-related macular degeneration to receive a placebo or three intervention groups. The treatment and findings of each are listed below;
- Antioxidants (vitamin C 500 mg, vitamin E 400 IU & beta carotene 15 mg) – No significant change
- Zinc (80 mg, as zinc oxide) and copper (2 mg, as cupric oxide) – No significant change.
- Antioxidants plus zinc/copper combined – Significant reduction.
Over an average follow-up period of 6.3 years, the supplements together significantly reduced the risk of developing advanced-age–related macular degeneration and reduced loss of visual acuity. These nutrients are present in most basic multi-vitamins and mineral supplements but usually in substantially smaller amounts.
Update 7th Feb 2017. Unfortunately there is amassing evidence as pointed out by several specialists that the above study has several hidden flaws which make its conclusions unreliable. The authors changed their study design part of the way through without declaring it, their omitted many participants from the final results which in essence manipulates the data and there were undeclared massive conflicts of interest. As such the medical evidence based upon anitioxidant supplements use in age related macular degeneration is flawed and no longer convincing.
Vitamin and anti-oxidant supplement studies in general may show benefit in specific areas such as animal studies, human tissue studies in laboratories and even human clinical trials involving an isolated illness (e.g. Eye disease). However several large scale vitamins and anti-oxidant supplement meta-analyses studies have failed to show over all benefit either singly or in combination to prevent all-cause death, heart disease, strokes and death from them and likewise prevent cancer (both in primary and secondary cancer and cardiovascular disease populations). The only exception to this is Vitamin D3 in the elderly population has shown to reduce all cause death (mortality) and further studies are awaited to see if this applies to younger adults and to determine the ideal dose.
There is strong evidence that supplements containing Vitamin A, Vitamin E and beta-carotene increase deaths and so should be avoided at this present time.
There is strong evidence that those with cancer should avoid vitamin and anti-oxidant supplements due to the increase risk of bladder cancer. Although this is the general principle you should however discuss this with you oncologist to see if it applies in your case. It is thought that synthetic anti-oxidants in this situation help to protect the cancers. More studies are needed in those without cancer before we can say it applies to that situation.
All of the above applies to supplements only and not to fruits, vegetables, nuts and healthy eating. There is convincing evidence (non conclusive) through observational studies that wholesome eating of fruit and vegetables does improve health and we may discuss these in a later post.
We have previously mentioned the PREDIMED study and Lyons-heart study which have shown Mediterranean diets and in particular olive oil and nuts that contain a variety of antioxidants to show hard evidence of improvement in heart disease (and reduction of metabolic syndrome). For example brazil-nuts are a good source of selenium and turning to supplements is not generally advised.
There will be exceptions to the general rule such as in infants, in the elderly, during pregnancy and your doctor will discuss these with you.
Vitamin D is from lack of sunshine and if your lifestyle and the region you live in may make this deficiency manifest which is very common in the UK then Vitamin D3 supplements may be advised or even prescribed by your doctor. In US milk products are supplemented with Vitamin D which will make it less of a public health problem.
The dangers of following unproven therapies even though those who advocate them are recognised scientists. If the therapy works then getting proof for it should likewise be possible. Don’t be duped by quackery!