Some of the most popular supplements on the market may be actively damaging blood vessels — yet millions of people take them daily without any awareness of the risk.
It is not just one supplement. Research on five commonly used supplements shows they may do more harm than good. Here is what the human evidence says about each one, and what to consider instead.
The pattern across all five is remarkably consistent: each supplement fills a genuinely important biological role, which is why they became popular in the first place. The problem is not the nutrient itself — it is the form in which it is delivered. Supplements bypass the regulatory mechanisms that normally govern how these compounds enter the body, and that distinction turns out to matter enormously.
Table of Contents
Calcium
Calcium is one of the most abundant minerals in the human body. It is required for muscles — including the heart — to function properly. It is vital for nerve signalling, and healthy bones cannot form without it.
Despite its essential role, calcium supplements carry poorly understood risks that have accumulated in the scientific literature over the past two decades.
The rationale for calcium supplementation has long seemed compelling. Bone loss is a real and serious problem, particularly in older adults, where declining bone mass raises the risk of fractures and osteoporosis [1].
The risk is especially pronounced for women after menopause. Because of hormonal changes, they experience accelerated bone loss at a rate of 3–5% per year for several years [2].
Why does bone loss occur? Bones are constantly undergoing remodelling — cellular processes break down old bone and construct new bone. It is like a road that is constantly being torn up and repaired. With age, the repair process slows. At some point, the balance tips and more bone is lost than rebuilt. Calcium is a key building material. For several reasons, including decreased absorption, maintaining adequate calcium supply becomes harder with age.
So ensuring adequate calcium intake is a reasonable goal. Taking calcium supplements seems like the most straightforward way to achieve it.
Health is complex, however. What appears logical does not always work as expected. The research on calcium supplements has produced surprising results. Clear benefits in terms of reduced fracture risk were anticipated. The results are mixed at best.
One meta-analysis found several studies reporting reduced fracture risks with calcium supplements [3]. Yet many of those studies had a significant risk of bias. When researchers isolated only randomised controlled trials with the lowest risk of bias, the picture changed considerably. The calcium supplements did not appear to help at all [4].
So the benefit is unclear. At the same time, evidence of potential harm has been accumulating steadily.
Several studies have produced concerning results. One early meta-analysis in 2010 pooled results from trials of calcium supplements. Researchers discovered that those taking the supplements had approximately a 30% increase in the rate of heart attacks [5].
Numbers from a more recent cohort study were even more striking. This study involved people with osteoporosis in South Korea. Researchers found that those taking calcium supplements without vitamin D had almost 90% higher risk of a heart attack [6].
Vitamin D is relevant here because it plays a critical role in regulating calcium in the body. Inadequate vitamin D appears to make the risks associated with calcium supplements worse.
A further study investigated the association between calcium intake and mortality in a large cohort of women in Sweden. Consistent with the other findings, high calcium intakes were associated with higher all-cause and cardiovascular death rates [7].
What is the underlying mechanism? Scientists suspect calcium supplements produce an acute spike in blood calcium levels. Higher circulating calcium makes calcification of arterial walls more likely [8].
In addition to restricting blood flow, arterial calcification reduces vascular flexibility — arteries become less able to expand and contract in response to changes in pressure. Elevated calcium can also affect blood clotting. Together, these effects raise the risk of cardiovascular events.
Does this mean calcium should be avoided entirely? No — it is an essential nutrient. The recommended daily allowance is over 1,000 mg per day for adults. But how that calcium is obtained makes a significant difference.
There are essentially two options: supplements or dietary sources (or a combination). For most people, obtaining calcium from food is the preferable approach.
The current working theory is that the negative cardiovascular effects of calcium supplements stem from the way they acutely spike blood calcium levels. Crucially, dietary calcium does not appear to produce this acute spike [9].
If that mechanism is correct, the prediction follows logically: increased heart disease risk should appear with calcium supplements but not with dietary calcium. The evidence supports this prediction.
One large cohort study examined arterial calcium buildup and how it changed over 10 years. Those with the highest total calcium intakes had a 27% lower risk of developing arterial calcification. At the same time, supplement users had a 22% higher risk of calcification compared to non-supplement users [10].
When the data were stratified by supplement use and total intake, the highest-risk group was supplement users with low total calcium intake. The lowest-risk group was non-supplement users with the highest total dietary calcium intake [11].
This evidence strongly supports the conclusion that the source of calcium matters. Supplements present risks that do not appear to arise from dietary calcium.
A further study confirmed the same pattern. Calcium supplements raised the risk of cardiovascular death in men, while dietary calcium intake had no such negative impact [12].
When specifically examining blood vessel health, calcium supplementation has been linked with increased progression of vascular calcification in people with existing coronary artery disease. An analysis of data from nine previously conducted clinical trials involving 5,147 people found that the odds of calcification progression were 15% higher for those who used calcium supplements compared to those who did not [13].
What about at-risk populations who appear to need extra calcium? A large study of elderly patients in managed care facilities demonstrated that boosting calcium from food sources — adding high-calcium foods like milk, yogurt, and cheese to achieve over 1,000 mg per day — reduced the risk of bone fractures by 33% [14]. Dietary enrichment, not supplementation, drove the benefit.
There are some individuals who may genuinely require calcium supplements. Vegan women, for instance, face a higher fracture risk without them because they are not consuming dairy — one of the primary dietary calcium sources [15].
But for most people, boosting dietary calcium intake is a safer way to meet requirements without raising cardiovascular risk.
Iron
Calcium is not the only supplement linked to potential harm. Four others share a similar profile — genuinely important roles in the body, but real risks when taken as supplements without confirmed need.
Iron is the first. It is required for transporting oxygen in the blood, producing cellular energy, and supporting proper muscle function. Deficiency manifests as fatigue, weakness, and cognitive impairment.
With supplements, however, excess intake is easy to achieve. At a mild surplus, iron can reduce levels of zinc — another essential mineral — and cause gastrointestinal upset [16].
High doses of iron are substantially more dangerous and can lead to serious organ damage [17].
As with calcium, the safest approach for most people is obtaining iron through the diet. Adult men need 8 mg per day; women need 18 mg until menopause. The most bioavailable form is haem iron, found in animal sources — beef and seafood are both high in iron. Plant-based options include leafy green vegetables, white beans, and lentils, though absorption from these sources is lower.
Certain groups face a genuinely elevated risk of iron deficiency: pregnant women, those with heavy menstrual periods, and people with specific digestive conditions such as coeliac disease or inflammatory bowel disease. These individuals may need supplementation. However, iron supplements are most appropriately used at the direction of a healthcare professional, following blood testing to confirm actual deficiency, rather than taken preventively. Supplementing iron without confirmed deficiency confers no benefit and carries real risks.
Vitamin E & A
Next is vitamin E — a popular antioxidant found naturally in vegetable oils, nuts, seeds, and green leafy vegetables such as spinach. It is claimed to protect cell membranes, potentially reduce cancer risk, and extend lifespan. Supplement manufacturers have promoted it heavily on the basis of these claimed effects.
The evidence does not support those claims. Here is why.
First, vitamin E deficiency is rare except in individuals with specific health conditions. The vitamin is widely available in food, so most people already obtain sufficient amounts through their diet.
Second, excess vitamin E can interfere with the benefits of exercise [18]. This is a significant concern given that physical activity is one of the most powerful contributors to long-term health outcomes.
Third, there is a troubling possibility that supplemental vitamin E may shorten rather than extend lifespan. An in-depth Cochrane analysis of 78 clinical trials involving nearly 300,000 participants found no evidence that antioxidant supplements reduce mortality. The analysis found that vitamin E supplementation may actually be associated with increased mortality [19] — the opposite of the marketed benefit.
It also appears that the form of vitamin E matters. The vitamin exists in eight forms: four tocopherols and four tocotrienols [20]. Tocotrienols appear to offer a greater antioxidant effect in laboratory studies [21].
Some commentators have argued that the large safety-signal trials did not specifically examine tocotrienols, and that their conclusions therefore should not apply to that form. That is an interesting hypothesis — but it requires rigorous testing before any claim of safety can be made. Long-term safety data on tocotrienols does not currently exist. Furthermore, tocopherols and tocotrienols act through broadly similar mechanisms; both function as antioxidants. The existing trial data shows no meaningful signal that any form of vitamin E extends lifespan. Instead, the concern is that it may shorten it. High-dose vitamin E supplementation has also been shown to increase the risk of prostate cancer [22].
Before supplementation with tocotrienols could be recommended, robust long-term safety evidence would be required — and that evidence does not currently exist.
The same Cochrane analysis that raised concerns about vitamin E also highlighted vitamin A. At higher supplemental doses, vitamin A appears to be associated with increased mortality [19]. A separate study found that excess vitamin A can weaken bones, damage the liver, and cause birth defects [23].
As with vitamin E, deficiency of vitamin A is uncommon in well-nourished populations. Dietary intake from foods such as liver, eggs, dairy, and orange and yellow vegetables provides adequate amounts for most people without supplementation.
The central problem with both vitamin E and vitamin A is that the doses achievable through supplementation far exceed what is attainable from a normal diet. The human body evolved regulatory mechanisms — absorption limits, conversion controls, storage ceilings — that manage dietary micronutrients. Supplements can bypass these controls, and the evidence suggests that when they do, harm can follow.
From the MicroVitamin range
MicroVitamin deliberately excludes both vitamin E and vitamin A. The current evidence does not support routine supplementation of these vitamins for most people, and the available data raises real concerns about potential harms. Learn more about the evidence-based ingredient decisions behind MicroVitamin.
Resveratrol
Finally, resveratrol — one of the most heavily marketed supplements in the area of extending lifespan [24].
The proposed mechanism centres on an enzyme called SIRT1, which functions as a control switch for many important cellular processes. It helps regulate stress response, inflammation, and the repair of damaged DNA. For these reasons, it has been linked to the biology of ageing. Researchers initially believed that increasing SIRT1 levels in various organisms extended their lifespan [25].
Scientists searched for a compound capable of boosting SIRT1 levels, hoping this might translate to longer lifespans in humans. One early study identified resveratrol as a candidate, claiming it extended the lifespan of yeast by 70% [26].
That finding generated enormous enthusiasm for resveratrol. It later emerged, however, that those initial results were the product of a laboratory error.
That revelation should have substantially dampened interest in resveratrol. Researchers continued investigating it regardless. So far, results have been consistently disappointing.
When the rigorous Interventions Testing Program studied resveratrol, no beneficial effect was found. The program confirmed that resveratrol was absorbed into the bloodstream — ruling out a bioavailability issue. The compound simply did not produce the hoped-for effects [27].
Disappointing results have also emerged for other proposed benefits. Some researchers suggested resveratrol might help manage type 2 diabetes. A Cochrane analysis found no support for that claim in the current literature [28].
Resveratrol does have measurable cellular effects — but not beneficial ones. A study using CRISPR technology examined whether resveratrol activates SIRT1 and found that it does not [29]. Instead, resveratrol stresses cells and interferes with the DNA copying process during cell division. If normal DNA replication is like smoothly copying pages from a book, resveratrol makes that process slower and more error-prone — analogous to copying with a malfunctioning machine.
There appeared, at first, to be a possible silver lining relating to exercise.
The reasoning was as follows. Exercise stresses cells, and that stress is beneficial — it signals cells to become stronger and more efficient. Researchers proposed that combining resveratrol with exercise might amplify this cellular stress and thereby increase the benefits of training.
The opposite turns out to be true. One study examined 27 men who completed high-intensity exercise training. Resveratrol supplementation reduced the positive effect of training on blood pressure, blood cholesterol, and cardiovascular efficiency [30].
There is also clinical evidence that resveratrol can reduce testosterone levels [31]. Lower testosterone is associated with a higher risk of death, particularly among older men [32].
At this point, there is no good evidence of beneficial effects from resveratrol in terms of lifespan or health outcomes. There is, however, evidence of potential harm. Resveratrol supplementation does not represent a sound strategy based on the current data.
The story of resveratrol is in many ways a cautionary tale about how supplement marketing can race ahead of evidence. A plausible mechanism (SIRT1 activation), an early dramatic result (70% lifespan extension in yeast), and substantial commercial investment generated years of consumer interest before rigorous human testing was done. When that testing arrived — through the Interventions Testing Program and multiple Cochrane analyses — the results were uniformly negative. The hype had no foundation.
Across all five supplements covered here, the evidence consistently points in the same direction: for most healthy adults obtaining adequate nutrition from food, supplementing with calcium, iron, vitamin E, vitamin A, or resveratrol carries risk without demonstrated benefit. Identifying which supplements are genuinely warranted — and which are not — is one of the most important decisions anyone can make when designing a supplement routine.
References
1. https://www.nature.com/articles/s41413-024-00346-4
2. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486688
3. https://www.bmj.com/content/351/bmj.h4580
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16. https://ods.od.nih.gov/factsheets/iron-HealthProfessional/
17. https://ods.od.nih.gov/factsheets/iron-HealthProfessional/
18. https://ods.od.nih.gov/factsheets/ExerciseAndAthleticPerformance-HealthProfessional
19. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007176.pub2/full
20. https://www.bocsci.com/resources/vitamin-e-tocopherols-and-tocotrienols-and-their-derivatives.html
21. https://pmc.ncbi.nlm.nih.gov/articles/PMC1790869/
22. https://pmc.ncbi.nlm.nih.gov/articles/PMC4169010/
23. https://jamanetwork.com/journals/jama/fullarticle/2793446
24. https://www.lifeextension.com/vitamins-supplements/item02210/resveratrol
25. https://pubmed.ncbi.nlm.nih.gov/24011076/
26. https://pubmed.ncbi.nlm.nih.gov/12939617/
27. https://pmc.ncbi.nlm.nih.gov/articles/PMC3598361/
28. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011919.pub2/full
29. https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30476-7
30. https://pmc.ncbi.nlm.nih.gov/articles/PMC3810808/
