Contrary to popular belief, too many vitamin supplements may do more harm than good to your health. By Michael Lim
IT is not uncommon to see patients armed to the teeth with a wide array of vitamins in the belief that vitamin supplementation will improve their health. For most city-dwellers who generally have good nutrition, the question is whether vitamin supplementation is beneficial or harmful.
In looking at the evidence for vitamins, it is important to distinguish between epidemiological studies which look at trends and can produce different outcomes when compared with well-designed trials where participants are randomised to the vitamin or placebo (randomised controlled trials or RCT). RCT is considered as the “gold” standard of clinical studies.
Vitamin A and beta-carotene
Beta-carotene is the active form of Vitamin A and is a fat-soluble antioxidant and levels tend to build up in the body with excessive consumption. Foods that are extremely high in beta-carotene include cod liver oil, goose liver, beef liver and chicken liver. Food sources which contain a high beta-carotene content include carrot, sweet potato, spinach, lettuce, tomato, papaya and mango.
A 2003 Lancet journal publication by Vivekananthan involving the combined analysis of data from 3 RCTs of beta-carotene in a total of more than 82,000 participants showed that beta-carotene intake did not have any beneficial impact on stroke but was instead associated with an increased risk of death from heart disease and total death. Animal studies have also shown that excessive beta-carotene intake also causes calcification of the aortic heart valve. Hence, vitamin supplements containing Vitamin A and beta-carotene should be avoided.
Vitamin C is another antioxidant but, unlike beta-carotene, it is water-soluble. There have been three RCTs which compared Vitamin C consumption with placebo. The Heart Protection Study which studied more than 20,000 patients with pre-existing stroke or heart disease, who were given antioxidant vitamins (Vitamin E, Vitamin C and beta-carotene) or placebo, did not show any beneficial impact of vitamin supplementation on stroke or heart disease after five years.
The effect of Vitamin C has also been evaluated separately in men and women. The Women’s Antioxidant Cardiovascular Study studied more than 8,000 females with multiple risk factors of heart disease or pre-existing heart disease who were given antioxidant vitamins (Vitamin E, Vitamin C and beta-carotene) or placebo. The Physicians’ Health Study II compared more than 14,600 males who were given Vitamin E and/or 500 mg of Vitamin C daily versus placebo. Both studies did not show any beneficial effects of vitamin supplementation. The current data do not support the use of Vitamin C supplements for the prevention of stroke or heart disease in middle-aged and older women and men.
Vitamin E is a fat soluble antioxidant that occurs naturally in eight different forms of which alpha-tocopherol is the main form in the body. Rich sources of alpha-tocopherol include nuts, seeds, vegetable oils and green leafy vegetables.
A meta-analysis of 13 RCTs of Vitamin E in more than 166,000 patients showed no significant benefit of Vitamin E in the prevention of stroke, irrespective of the source and dosage of Vitamin E and baseline health status. Overall, there is no evidence to support the use of Vitamin E supplements to prevent stroke or heart disease.
Animal studies have shown that high alpha-tocopherol levels can cause bleeding. In the 2008 Physicians Health Study II on Vitamin E in almost 15,000 healthy physicians, the use of Vitamin E was associated with a higher risk of stroke with brain bleeding. This risk of bleeding in the brain was also seen in another trial on Finnish males who took Vitamin E.
Other studies which showed adverse outcomes with Vitamin E intake include the HOPE-TOO (Heart Outcomes Prevention Evaluation Study Extension) study – which found that those on Vitamin E were 21 per cent more likely to be hospitalised for heart failure and the Women’s Angiographic Vitamin and Estrogen study in postmenopausal women with heart artery disease, which found that the total death was significantly higher in women taking Vitamin E. Two meta-analyses of RCTs have also shown an association between Vitamin E supplementation and increase in all-cause mortality.
Another potential adverse outcome of Vitamin E supplementation is the risk of cancer. The SELECT trial (Selenium and Vitamin E Cancer Prevention Trial) on vitamin supplementation on more than 35,000 patients was discontinued early as the supplements did not prevent prostate cancer.
Follow-up data demonstrated a 17 per cent increased risk of prostate cancer compared to those on placebos. Analysis of the latest 2014 SELECT data showed that men who started the trial with high levels of selenium doubled their risk of developing a high-grade prostate cancer by taking selenium supplements and men who had low levels of selenium at the start of the trial doubled their risk of high-grade prostate cancer by taking Vitamin E. Hence, Vitamin E supplementation should be avoided.
Homocysteine is a blood protein component and excessive amounts in the blood is associated with clogging of arteries in the heart, brain and legs. B vitamins, especially Vitamin B6, Vitamin B12 and folic acid, help to break down and reduce the blood homocysteine in the body.
Studies have shown that folic acid and Vitamin B12 supplementation can reduce the homocysteine level by 25 per cent and 7 per cent respectively. However, meta-analysis of RCTs of folic acid supplementation have not been able to demonstrate any benefit in preventing stroke or heart disease.
However, some physicians still consider that those at high risk of heart disease should ensure that they have sufficient amounts of these vitamins in their diet by eating fruits and green, leafy vegetables daily. For years, physicians have given patients high doses of Vitamin B3 (niacin) to raise high-density lipoprotein (HDL) cholesterol or “good” cholesterol levels. However, two major niacin supplementation trials, the HPS2-THRIVE and the AIM-HIGH study, have failed to show any benefit despite elevation in HDL cholesterol levels.
The AIM-HIGH trial was stopped prematurely as there was an increased incidence of stroke. Not only did niacin show no benefit, but there was also a high incidence of adverse effects. For non-diabetics, there was a significant risk of developing diabetes and for diabetics, there was a significant risk of impaired sugar control.
In addition, there were also multiple side effects including flushing and bleeding. Given the significant “toxicity” of high-dose niacin and the lack of RCT evidence, many experts have advised against the use of niacin for heart disease.
RCTs on Vitamin D supplementation have showed no significant beneficial effect on stroke, heart attack or death and had no impact on lipids, glucose or blood pressure. When Vitamin D and calcium were combined, there was an increased incidence of kidney stones.
However, Vitamin D supplementation appears to be beneficial for preventing osteoporosis and reducing the likelihood of developing diabetes. Hence, the appropriate dose supplementation does appear to have other benefits.
Calcium should not be given in combination with Vitamin D unless there is evidence of calcium deficiency, as combined supplementation may increase the likelihood of kidney stone formation and calcification of the arteries of the heart and brain. Current evidence from RCTs do not show any evidence that vitamin supplementation can prevent stroke or heart attacks. Before you pop in your vitamin pills, here are a few reminders:
• Supplementation of vitamins such as Vitamin A, niacin and Vitamin E have been reported to be associated with increased adverse outcomes and should generally be avoided;
• Consumption of water-soluble vitamins such as Vitamin C, folate and Vitamin B12 appear to be safe;
As low Vitamin D levels appear to be more prevalent, even in the tropics, Vitamin D supplementation may help to reduce the risk of osteoporosis;
• Unless there is dietary calcium deficiency, Vitamin D supplementation should be done without calcium, as calcium supplementation can predispose one to kidney stones, heart disease and stroke;
• For those with abnormal heart rhythms or artificial heart valves who are on blood-thinning medication which are Vitamin K antagonists (such as warfarin), intake of Vitamin K will reduce the effectiveness of the medication and hence increase the risk of blood clot formation which may result in stroke or failure of the artificial valve. Hence, as Vitamin D supplementation can be useful or harmful, do watch what you eat.