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Too Much of a Good Thing? The Risks of Excessive Supplementation

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Highlights
  • Vitamins and minerals are micronutrients, which means they are needed by the body in only tiny amounts
  • Most micronutrients that aren’t used by the body are eliminated in human waste, so excessive amounts are “wasteful” in many ways
  • For some vitamins and minerals, consuming large amounts can cause toxicity, or poisoning

Whoever said “You can’t have too much of a good thing” didn’t know much about dietary supplements. (That person was also probably never under a stay-at-home order that started out as an unexpected sabbatical of good books and daily yoga, but quickly devolved into a miasma of sweatpants and Instagram scrolling. Just me?) Vitamins and minerals are micronutrients, essential chemicals that the body requires only in very small amounts. When taken in abundance, the excess vitamin or mineral can result in anything from expensive pee (i.e., you simply pee it out) to tissue damage, or worse. 

During cold and flu season (or the odd viral pandemic), it’s tempting to take larger amounts of supplements with the intention of bolstering your immune system. Indeed, there is clinical evidence that a few vitamins and minerals can be useful in amounts greater than the recommended dietary allowance (RDA),1 particularly during immune challenges. However, in order to avoid adverse effects and possible toxicity, it’s important not to exceed the tolerable upper intake level (UL),1 unless directed otherwise by your physician. Be sure to account for dietary sources of micronutrients; if your diet already contains significant levels of particular micronutrients, you may not need to supplement at all. 

Rather than over supplementing in the interests of a stronger immune system, this article can help you choose doses that truly support your health and avoid wasting money on high doses of nutrients that your body doesn’t need and can’t properly utilize. 

Too much Vitamin C

Of all the vitamins we require, vitamin C has the largest RDA—90 mg for non-smoking adult men, and 75 mg for non-smoking adult women (smokers require an additional 35 mg).2 Vitamin C is not only a major antioxidant, but it’s also required for many essential biosynthetic reactions (collagen, neurotransmitters, carnitine, peptide hormones), and is required to stabilize enzymes that use iron and copper.2,3

As an antioxidant, vitamin C directly neutralizes reactive oxygen species, and regenerates the antioxidative activity of vitamin E.2 Vitamin C also supports the health and function of immune cells, and is preferentially transported into leukocytes, where it protects these cells during active immune reactions. For example, vitamin C protects neutrophils from damage during the oxidative burst that destroys pathogenic bacteria and viruses.2,4

Based on this bit of information, vitamin C may sound like something you want a lot of. But your small intestine can’t absorb a lot of vitamin C. When you consume amounts above 1000 mg, the small intestine only absorbs about 50%.2,5 So what happens to the vitamin C that isn’t absorbed? To be blunt, you poop it out. And, above the UL of 2000 mg per day, vitamin C may give you nausea, abdominal cramps, and diarrhea.2 In fact, a common bowel preparation for colonoscopy uses large amounts of vitamin C to enable complete evacuation.6 Good times.

However, sometimes your body does need extra vitamin C. In times of oxidative stress, (such as infection,7,8 smoking,9,10 poor air quality,11,12 and poor diet1315), the ability of vitamin C to be an antioxidant is quickly exhausted, and the blood (plasma) concentration of vitamin C decreases. When the plasma concentration decreases, the body compensates by increasing the intestinal absorption of vitamin C. So, yes, take some extra vitamin C when you get sick! But not too much.

Other adverse effects of excess vitamin C have been observed in preclinical studies, but have not held up under controlled clinical studies.2 These effects include increased formation of kidney stones and dangerous levels of iron absorption. Although none of these effects has been observed in healthy individuals, those with kidney disease, a history of kidney stones, or high blood levels of iron (hemochromatosis) should consult their physician before exceeding the RDA for vitamin C. 

Vitamin fun fact: Humans are among the few animals that can’t make their own Vitamin C! This exclusive club also includes fish, primates, bats, guinea pigs, and songbirds.16

Too much Zinc

When you hear “zinc”, you probably think about its role in decreasing the duration of the common cold. Many clinical studies have demonstrated the benefit of zinc supplementation for improving immune responses to viral infections like the common cold,17 as well as bacterial18 and fungal19 infections. 

Zinc influences immune function in many ways, including activation of adaptive immunity and promoting DNA stability.20,21 But macrophages win the award for the most creative use of zinc—they use zinc as both a weapon and a healer. As a weapon, macrophages use zinc to produce toxic reactive oxygen species molecules that destroy microbial invaders. As a healer, macrophages release zinc from intracellular storage to counteract the increased levels of reactive oxygen species once the invader has been eliminated.22

The UL for zinc is 40 mg/day for both women and men.23 Above this level, zinc competes with copper for absorption in the small intestine. And like a Vegas casino, zinc always wins. The symptoms of zinc-induced copper deficiency include fatigue, weakness, poor coordination and balance, frequent infections, and poor wound healing. Your physician may find that you have low red blood cells (anemia), low neutrophils (neutropenia), and neurological impairment (ataxia). Importantly, these signs and symptoms can develop in only a matter of weeks. 

Too much zinc may also compromise the ability of the immune system to fight bacterial and fungal infections. This is because of an often-overlooked component of the innate immune system called nutritional immunity. Nutritional immunity refers to a phenomenon that occurs when the body responds to a bacterial or fungal infection in the blood. (It doesn’t seem to occur with viral infections.24

Nutritional immunity works like this: As the immune system begins to respond to the infection, nutrient metals (like zinc, iron, manganese) are quickly transferred from the plasma into immune cells, thus ‘hiding’ them from the invading microbe. This is advantageous for our immune health because, just like us, microbes require nutrient metals to survive. When infectious microbes receive restricted access to nutrients, this limits their ability to reproduce. As a result, this limits the size and growth of infections, making them easier for the immune system to clear. Thus, taking excessive zinc (or other nutrient metals) during such an infection may actually give infectious microbes an advantage if it inadvertently provides them with the nutrients they need to grow. 

Too much Vitamin D

Vitamin D, also known as the sunshine vitamin, the bone vitamin, and Heavy D (okay, that last one was a rapper) plays a number of essential roles within the body. Well known as a central nutrient for bone health, vitamin D has gained a lot of attention in recent years for its critical roles in supporting immune health. To learn how vitamin D interacts with the immune system, what vitamin D3 is, and tons of other D-related info, check out this article.

While vitamin D toxicity is rather rare, it can occur after long-term supplementation with very high doses of dietary supplements (not from sun exposure or food).25 A normal function of vitamin D is to stimulate bone turnover, which releases calcium into the bloodstream. Thus, the symptoms of vitamin D toxicity are actually related to high levels of calcium in the blood and urine.26 These symptoms include dehydration, excessive thirst, excessive urination, vomiting, abdominal pain, and confusion. Even worse, all the extra calcium in the blood and urine is coming from your bones, and accumulates inside organs like the heart.    

Vitamin D3 is a fat-soluble molecule, which means that it gets stored in the body where fat is. This includes tissues like…the liver! (Admit it, you thought I was going to say the butt. Well, actually, it goes there too.) And as we know, fat stays stored for a long time. Because vitamin D can remain stored in fatty tissues for so long, consuming large excesses of vitamin D can be difficult to treat clinically. In fact, vitamin D-induced hypercalcemia can last over a year for this reason.25 So be careful when choosing your dose, as this is not an easy mistake to correct. 

The adult UL for vitamin D was set at 4000 IU/day in 2010. However, it should be noted that this value was set before the knowledge of genetic variations that affect vitamin D levels in the blood.2729 Due to these variations, some people may need to supplement more or less than others. The only way to know whether or not your vitamin D intake is optimal is to get blood testing. Thus, the best approach is to work with your physician to arrive at a healthful dose. 

Too much Selenium

Selenium is like a coffee mug with your pet’s face custom-printed on it—you know you need it, but you’re not sure why. Selenium is a mineral that we require for the production of molecules called selenoproteins. There are 25 selenoproteins encoded by the human genome, and they serve extremely important roles as antioxidants and regulators of thyroid hormones3032 One of these selenoproteins actually turns reactive oxygen species into water!32 (Move over, David Copperfield). 

Like vitamin C, selenium (as selenoprotein) helps protect immune cells from oxidative damage during immune reactions. Not surprisingly, low levels of selenium are associated with increased susceptibility to infections and greater symptom severity.33 Fortunately, it’s rather easy to get selenium from the diet; a single brazil nut contains 96 ug of selenium, almost twice the adult RDA of 55 micrograms (ug)/day.2 But don’t go nuts—consuming too much selenium from foods or supplements can be toxic. 

The UL for selenium is 400 ug/day for adults.2 If taken over a relatively short period of time (i.e., days to months), consuming very large amounts of selenium (100 times the UL), are reported to cause nausea, diarrhea, joint pain, thick and brittle nails, breath and skin that smell like garlic, and partial or complete hair loss.2,34 Evidence suggests that these toxic effects are due to selenium actually causing (rather than neutralizing) reactive oxygen species at high doses.35

But what about smaller excesses over a period of years? A recent well-designed clinical study (randomized, double-blind, placebo-controlled) examined the mortality rates of 491 older Danish adults (60-74 years old) taking selenium for 5 years.36 The researchers found that those taking 300 ug/day for 5 years had significantly greater all-cause mortality 10 years later (15 years from the start of study), compared with those who took 100 ug/day, 200 ug/day, or a placebo (the latter three conditions had similar mortality rates). This illustrates that, at least for selenium, even when you stop taking excessive levels of a supplement, it can continue to impact your health well into the future. 

So how much is safe over the long haul? As mentioned above, the 15-year study found that those taking 100 ug/day and 200 ug/day had similar mortality rates compared to placebo. It is estimated that Americans consume an average of 100 ug/day in the diet, due to the high selenium content in our agricultural soils.2 This is good news, since clinical data indicates that maximum production of selenoproteins occurs around 100 ug/day.37 The daily dose of most selenium dietary supplements contain 200 ug, which is a common dose used in clinical trials. While this is a good number to shoot for, the best approach to safe selenium intake is to work with your physician to determine the amount of selenium you need to get your blood levels in a healthy range.

In Closing

To summarize, nutrient-dense foods are the best way to acquire most nutrients, and much less likely to lead to excess micronutrient intake than supplements. However, given that food allergies, aversions, and issues with availability can make it difficult to acquire everything you need from diet alone, supplementation with certain nutrients is often necessary. As always, discuss your use of dietary supplements with your physician, especially if you take medications and/or have medical conditions. 

Sharon Matheny, MSNS, PhD is Manager of Nutrition Science Communications for Nordic Naturals. She holds a doctorate in Cell and Molecular Biology, with specializations in cancer cell signaling and molecular neuroscience. After a career in biotechnology developing molecular diagnostics, she has found her calling in bringing evidence-based nutrition and health science information to the general public and health professionals.

Leukocytes: A general scientific term for “white blood cells”.

Macrophages: A type of leukocyte that engulfs and destroys microbes; similar to neutrophils.

Microgram (ug): 1/1,000,000 of a gram, 1/1000 of a milligram.

Neutrophils: A type of leukocyte that engulfs and destroys microbes; similar to macrophages.

Nutrient metals: Metals are atoms on the periodic table that have a particular arrangement of electrons. Nutrient metals are a small selection of these atoms that are critical for life.

Oxidative burst: The release of reactive oxygen molecules in order to destroy microbes that have been engulfed by specific types of leukocytes.

Plasma: The liquid part of the blood that contains clotting factors but doesn’t contain cells.

Preclinical studies: Non-human experiments that occur before clinical (human) experiments take place. These experiments usually involve animals, but may also include in vitro (not in organisms) experiments.

Reactive Oxygen Species (ROS): An unstable molecule containing oxygen that easily reacts with other molecules. High levels of ROS can cause damage to DNA, proteins, and cell membranes.

Recommended Dietary Allowance (RDA): The average daily level of intake sufficient to meet the nutrient requirements of ~97% of people without health issues. The RDA amounts for vitamins and minerals are set periodically by the National Institutes of Health.

Tolerable Upper Intake Level (UL): The maximum daily intake unlikely to cause adverse side effects or toxicity. The UL amounts for vitamins and minerals are set periodically by the National Institutes of Health.

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