Should we rely on Supplements?

Should you rely on supplements to meet your daily vitamin and mineral needs or could there even be potential side effects of taking supplements?
Supplementation has helped millions of people to reach adequate vitamin levels and helped to prevent severe disease like scurvy or rickets. [1]
For instance, Vitamin A deficiency can make you blind, being folate deficient before or during pregnancy can lead to birth defects in the baby, and being vitamin D deficient leads to weak bones.

 
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Vitamins and minerals are essential for our body. They are involved in almost every cellular process. However, in our modern society, many people lack adequate levels of these micronutrients, which makes the body run less optimal and the person more susceptible to diseases. [2, 3, 4]

Even though this sounds like supplementation is a great idea, the story is more complex than this. There are at least four factors we need to consider when we talk about supplementation:

  1. Bioavailability

  2. Effect

  3. Benefit

  4. Overdosing


Bioavailability

Let’s starts with bioavailability. A good example here is magnesium. A study found that magnesium citrate absorption was much higher than the absorption of magnesium oxide, which lead to the effect that you might entirely misjudge the amount of magnesium that you absorb. [5, 6]

Another example would be vitamin A. The common perception is that one carrot provides all the daily vitamin A you need but carrots actually don’t contain Vitamin A but beta-carotene, which is also often the “vitamin A” in supplements. Beta-carotne is a provitamine, that it needs to be converted into the active vitamin A.

Another thing is the absorption of beta-carotene can vary extremely. It is a fat-soluble vitamin meaning, it needs fat to be properly absorbed. A study from the Ohio state university found that the body formed more than 12 times as much vitamin A from carrots when they were eaten with avocado than when they were eaten alone because of the high fat content in avocados. [7, 8]

These are just a few examples to make you little bit more conscious that the form of the supplement matters and also the way you consume it.

Effect of the supplement

An entirely different question would be the effect of the supplement. We would expect that when we absorb and process the supplement that it should give us the promised benefits, right? Well, in many cases, yes… but calcium is a good example to why this is not always the case:

Dietary calcium has been shown to decrease the risk for heart diseases [9]. However, it seems to be the opposite for calcium supplements. In a randomized trial, Bolland and colleagues found that supplemental calcium significantly increases the risk for heart diseases. [10]

 
survival plot showing proportion of healthy postmenopausal women assigned to calcium supplementation or to placebo that had a verified myocardial infarction during the study [10]

survival plot showing proportion of healthy postmenopausal women assigned to calcium supplementation or to placebo that had a verified myocardial infarction during the study [10]

 

For the potential mechanism behind it - Dr. Ian Reid, senior author of the study, explains that when high amounts of calcium are consumed calcium blood concentrations shot up, which leads to an increase in blood pressure and higher blood clotting activity, which are both risk factors for heart diseases. [11, 12]

Benefits

By now, you might be wondering whether there are actually any benefits to supplementation. Well, it depends. As Eda and I explained in our video about Vitamin D, there have been some studies that show substantial benefits for vitamin D supplementation. At least when you are at a risk of deficiency to begin with.

Another good example for the benefits of supplementation is folic acid. Folate deficiency in the mother can lead to birth defects called neural tube defects, which are openings in the spinal column, leading to developmental problems or even death. Fortification of foods with the synthetic folic acid made the rate of neural tube defects drop extremely. [13]

A meta-analysis of randomized trials found that it reduced the risk by about 70-90%, which is great but the question here is:
Why not 100%? [14]

Well, it is complicated - synthetic folic acid is not the natural folate and needs to be converted into 5-methyl-tetrahydrofolate, or short methylfolate to be useful and many people seem to have genetic mutations in the enzymes that catalyse these reactions, which adds another layer of complexity to this whole topic. [15, 16]

Okay, what about vitamin C? It is one of the most supplemented vitamins and everyone takes it when sick or when trying to prevent a cold. But here is the thing; Studies fail to back that up.
Apparently, there is no evidence that vitamin C prevents the frequency of catching a cold and only shortens the duration of the cold by about half a day. [17, 18]

To be fair, in people who do intense sports the risk of getting a cold was halved by vitamin C supplementation, probably because vitamin C acts as an antioxidant that helps to cope with stress.

Talking about antioxidants: We have all learned that antioxidants are good for us and getting a decent amount of different antioxidants from food sources is most likely a good idea but a meta-analysis from 2018 looked at 21 studies using antioxidant supplements and found a slight but significant increase in all-cause mortality in the group of people that consumed antioxidants. So the exact opposite of what we would expect. [19

 
Effects of commonly used Supplements on All-cause Mortality [19]

Effects of commonly used Supplements on All-cause Mortality [19]

 

For the potential mechanism; sometimes it is necessary to produce reactive molecules in the body as they fulfil important tasks like immune defences or kill cancer cells. [20, 21]

Only chronically high levels might be harmful but sometimes you might need a kind of a shock to get things going and don’t want tons of antioxidants to interfere with it.

It is like taking a cold shower. This little shock might help the body to handle stress better throughout the day.

 
Reactive oxygen species and cancer paradox: To promote or to suppress? [20]

Reactive oxygen species and cancer paradox: To promote or to suppress? [20]

 

Overdosing

Another issue with supplementation is overdosing. There are cases where acute overdosing caused severe health problems. [22, 23]
However, chronic overdosing might be the bigger issue. One problem with chronic over dosing is that it most likely affect the concentration of another vitamin or mineral.

These interactions can get really complex. A good example for that is the so-called mineral wheel. If you have to much of a certain mineral, it can cause a deficiency of the mineral it’s arrow is pointing to. So, excess cupper can lead to zinc deficiency, excess phosphorus leads to calcium deficiency and so on.

 
mineral dependencies.gif
 

This is nicely illustrated in an 1985 paper. When turkey where fed a diet high in either vitamin A or vitamin D the birds got sick of hypervitaminosis, but when fed a diet containing high levels of both vitamins A and vitamin D, growth rate and bone mineral content were similar to the control [24]

There is much more to say about this topic but the purpose of this blog is not to tell you what supplement you should use but to confuse you a little bit and make you aware of the complexity.

By default, you should try to cover your needs by real food as we have seen that supplements sometimes do unexpected things. Food also supports the absorption and makes over dosing unlikely.

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References

  1. Bailey et al., Examination of vitamin intakes among US adults by dietary supplement use., J Acad Nutr Diet, 2012

  2. Forrest and Stuhldreher, Prevelance and correlates of vitamin D deficency in US adults, Nutr Res, 2011

  3. Miller JL, Iron deficiency and anemia: a commin and currable disease, Cold Spring Harb Perspect Med, 2013

  4. Green et al., Vitamin B12 deficiency, Nat Rev Dis Primers, 2017

  5. Lindberg et al., Magnesium bioavailability from magnesium citrate and magnesium oxide., J Am Coll Nutr.

  6. Schuchardt and Hahn, Intestinal Absorption and Factors Influencing Bioavailability of Magnesium-An Update, Curr Nutr Food Sci. 2017

  7. Kopec et al., Avocado Consumption Enhances Human Postprandial Provitamin A Absorption and Conversion from a Novel High–β-Carotene Tomato Sauce and from Carrots, J Nutr, 2014

  8. Tanumihardjo SA, Factors influencing the conversion of carotenoids to retinol: bioavailability to bioconversion to bioefficacy., Int J Vitam Nutr Res. 2002

  9. Anderson JJ, Kruszka B, Delaney JA, et al. Calcium intake from diet and supplements and the risk of coronary artery calcification and its progression among older adults: 10‐year follow‐up of the Multi‐Ethnic Study of Atherosclerosis (MESA). J Am Heart Assoc. 2016

  10. Bolland et al., Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial., BMJ, 2008

  11. Bristow et al., Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women, Br J Nutr. 2014

  12. Dr. Ian Reid: Unexpected side-effects from calcium supplements - https://youtu.be/lo3JyedmU2c

  13. https://www.aihw.gov.au/news-media/media-releases/2016/2016-jun/decrease-in-neural-tube-defects-since-folic-acid-a

  14. Grosse and Collins, Folic acid supplementation and neural tube defect recurrence prevention, Birth Defects Res, 2007

  15. Patanwala et al., Folic acid handling by the human gut: implications for food fortification and supplementation, Am J Clin Nutr, 2014

  16. Dr. Ben Lynch: Folic Acid is Affecting You Negatively - https://youtu.be/cWFPRI6X7P4

  17. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold . Cochrane Database Syst Rev. (2013)

  18. Douglas RM, et al. Vitamin C for preventing and treating the common cold . Cochrane Database Syst Rev. (2007)

  19. Jenkins et al., Supplemental Vitamins and Minerals for CVD Prevention and Treatment, J Am Coll Cardiol. 2018

  20. Yang et al., Reactive oxygen species in the immune system, Int Rev Immunol, 2013

  21. Galadari et al., Reactive oxygen species and cancer paradox: To promote or to suppress?, Free Radical Biology and Medicine, 2017

  22. Martins et al., Vitamin D intoxication: case report, Einstein (Sao Paulo), 2014

  23. Naz et al., Hypervitaminosis A; a case report, N Engl J Med, 2952

  24. Metz et al., The interaction of dietary vitamin A and vitamin D related to skeletal development in the turkey poult., 1985