Hypervitaminosis: how not to overdo supplements?

What is hypervitaminosis?

Hypervitaminosis is a condition in which a vitamin or vitamins accumulate in the body to a level that exceeds the body’s ability to excrete or metabolise them safely. This accumulation can be toxic, and the excessive amount of a vitamin in the body may also be described as poisoning with that vitamin. Hypervitaminosis applies to individual vitamins, and not to general oversaturation of the body with many different vitamins, although in theory this is possible.

The phenomenon of hypervitaminosis is not very common and virtually never occurs through diet alone. Nevertheless, it is a serious risk resulting from reckless supplementation.

Most importantly, not every excessive intake of a given vitamin or provitamin that produces certain symptoms is already hypervitaminosis. A slight excess of vitamins may be noticeable, but without serious symptoms suggesting toxic effects. One such case is carotenaemia – a darker skin pigmentation following high intake of provitamin A, i.e. beta-carotene. Hypervitaminosis, on the other hand, is a serious set of disease symptoms that can even be life-threatening.

Causes and the most common cases of hypervitaminosis

The most common cause of hypervitaminosis is improper supplementation. This may involve long-term intake of excessively high doses of supplements, or a single dose of a vitamin or vitamins that cannot be properly excreted or metabolised.

In theory, hypervitaminosis can concern all known vitamins. In practice, however, it mainly affects vitamins A, D, E and K, as well as vitamins from the B group. A, D, E and K are fat-soluble vitamins, and the body does not have efficient systems for excreting these vitamins in adequate amounts. Other vitamins, those that are water-soluble (B1, B2, B3, B5, B6, B7, B9, B12, C), are removed more efficiently from the body in urine, which is why it is more difficult to cause toxic excess of them.

Hypervitaminosis is most often triggered by excessive supplementation:

• Taking multiple preparations at the same time.
• Conscious or unconscious us of high vitamins doses.
• Unintentional duplication of ingredients in multi-ingredient supplements (e.g., vitamin D present in a multivitamin, in collagen, and in an ‘immunity booster’).

Hypervitaminosis resulting from a diet too rich in a given nutrient hardly occurs. Only a few cases have been described, usually associated with extreme dietary regimes such as the carnivore diet based on large amounts of offal.

Symptoms of vitamin excess and documented cases

Hypervitaminosis always applies to a specific vitamin and may have different symptoms and courses, depending on how the given vitamin is metabolised and stored in the body. Each type of hypervitaminosis has a distinct mechanism of toxicity, results in different symptoms, and can damage different organs.

1. Hypervitaminosis A

This disorder is caused by an excess of retinoids (retinol and its derivatives), which accumulate primarily in the liver. Liver cells (hepatocytes) have a limited capacity for storing retinol. Once this capacity is exceeded, retinol enters the bloodstream. It can be partially bound there by specialised transport proteins (retinol binding protein, RBP), but any excess will be present in its free form. Elevated retinol concentration (vitamin A) has cytotoxic effect on cells. It destabilises cell membranes, increases oxidative stress, and disrupts gene expression.

Hypervitaminosis A occurs in two forms:

1. Acute hypervitaminosis A – may result from a single intake of a very large dose of a supplement and produce the following symptoms:

• dangerous increase in intracranial pressure,
• nausea,
• irritability,
• scaling of the skin.

2. Chronic hypervitaminosis A – develops gradually, with long-term intake exceeding the requirement for vitamin A and the body’s limited ability to metabolise it, which may cause:

• hepatotoxicity – liver damage and fibrosis,
• headaches,
• hair loss,
• bones fragility (excess of vitamin A affects osteoclasts),
• visual disturbances,
• impaired muscle function,
• skin hypersensitivity and dermatological changes (alopecia, skin ulcers),
• loss of appetite,
• haemorrhages,
• cardiac dysfunction,
• kidney dysfunction,
• tumour formation.

An excess of vitamin A and hypervitaminosis are especially dangerous for pregnant women, because an overly high concentration of retinoids has a toxic effect on the foetus and interferes with the expression of genes crucial for embryonic development. Even a slight excess of vitamin A is harmful. Therefore, pregnant women are advised to exercise particular caution when supplementing vitamin A, as well as when consuming foods rich in this vitamin. For this reason, eating liver (a very good source of vitamin A) or using skin products containing vitamin A in the form of creams or ointments is discouraged.

Importantly, the risk of hypervitaminosis depends on the form of vitamin A consumed. Animal-derived vitamin A (e.g., retinol and its derivatives) is more likely to cause more dangerous hypervitaminosis. Beta-carotene, on the other hand, which is a provitamin converted into vitamin A in the body, is a safer form. In the case of excess beta-carotene, the body simply blocks its conversion into retinol. It may lead to harmless carotenaemia, manifested by a yellow-orange discoloration of the skin on the palms, heels, and elbows, which is reversible with reduced intake and usually does not cause other ailments.

The tolerable upper intake level (UL) for vitamin A for adults is 3000 μg per day (measured in retinol equivalents).

Described case: In 2006, the scientists from Mayo Clinic in Phoenix described the case of a 60-year-old patient with symptoms of muscle pain, alopecia and abnormalities in nail structure. Renal failure, ascites and deteriorating liver function were also diagnosed. Before the doctors managed to make a diagnosis, a liver transplant was necessary to save the patient’s life. The cause of the patient’s condition turned out to be the intake of high doses of vitamin A supplements recommended by a practitioner of alternative medicine.

2. Hypervitaminosis D

This toxic condition is caused by an excessive concentration of cholecalciferol (D3) or ergocalciferol (D2) in the body. The biggest problem is disruption of the body's calcium-phosphate metabolism. Vitamin D increases the absorption of calcium from the intestines, its reabsorption in the kidneys, and its release from the bones. Although these are natural processes, their excess leads to hypercalcaemia, which is an increased level of calcium in the blood.

Symptoms of acute hypervitaminosis D may include:

• nausea and vomiting,
• loss of appetite,
• myasthenia,
• dehydration,
• headaches,
• skin itching,
• increased thirst, more frequent urination,
• cardiac arrhythmias.

If hypervitaminosis D becomes chronic, additional complications may occur:

• nephrolithiasis,
• renal calcification,
• renal failure,
• cardiac arrhythmias,
• damage to blood vessels.

In children, hypervitaminosis D may lead to serious disturbances in bone mineralisation and growth, as well as delays in psychomotor development.

It is not possible to ‘overdose’ vitamin D from diet or due to exposure to sunlight. Although vitamin D is synthesised in the skin under the influence of UV radiation, its excess triggers its breakdown. This prevents overproduction of vitamin D and protects against hypervitaminosis as a result of sun exposure.

The tolerable upper intake level (UL) for vitamin D for adults is 4000 IU (100 μg) per day.

3. Hypervitaminosis C      

Vitamin C is one of the water-soluble vitamins. t must be supplied continuously, as the body has no efficient means of storing it. Due to the fact that it is constantly excreted, the body effectively protects itself against its excess and does not develop a classic form of hypervitaminosis that could endanger health. An excess of vitamin C is removed from the body with urine.

Nevertheless, excessive intake of vitamin C in supplement form may lead to health problems. These most commonly present as gastrointestinal complaints (diarrhoea, heartburn, nausea, bloating or abdominal pain). There are also documented cases of urticaria and rash following higher doses of supplements containing vitamin C. Usually, however, these do not require medical intervention and resolve spontaneously after the dose is reduced.

The daily dose of vitamin C in the form of supplement for adults should not exceed 2000 mg. Taking it in larger amounts over a longer period may increase the risk of nephrolithiasis and other health issues.

It is worth emphasising that no cases of ‘overdosing’ vitamin C from food intake have been documented.

Read more: Vitamin C in an athlete’s diet

4. Hypervitaminosis E

This condition is not common, although vitamin E is fat-soluble and therefore accumulates partially in the body. Hypervitaminosis E may occur when excessively high doses of supplements containing alpha-tocopherol (vitamin E) are taken, but it happens quite rarely. In comparison to vitamin A or D, vitamin E does not belong to the group of such popular supplements. The body also has a mechanism that partly protects against excess – around 60% of the daily dose of vitamin E is excreted in the faeces.

The main risk associated with excess vitamin E is its anticoagulant effect, i. e. reducing blood coagulability. Hypervitaminosis E therefore carries a risk of bleeding, including internal bleeding, particularly in people taking anticoagulant medications.

Symptoms associated with hypervitaminosis E include:

• persistent subcutaneous haematomas (‘bruises’),
• excessive bleeding, e.g. nosebleeds,
• headaches,
• visual disturbances,
• feelings of fatigue and weakness,
• digestive system dysfunction, including diarrhoea.

The tolerable upper level of vitamin E intake (from all sources) for adults is 300mg per day.

5. Hypervitaminosis K

This type of hypervitaminosis is relatively rare and does not occur through dietary intake of vitamin K.

The following forms of vitamin K are distinguished:

• K1 – present in plants (phylloquinone),
• K2 – obtained from fermented products (menaquinone),
• K3 – menadione, a synthetic form of vitamin K (rarely used in supplements intended for humans).

Vitamin K3 is particularly controversial and correlated with toxicity, as in excess it may induce oxidative stress in red blood cells. Excessive doses of vitamin K supplements may impair blood-clotting mechanisms and exhibit either procoagulant or anticoagulant effects – depending on the form and dose. This can lead to thrombosis and uncontrolled bleeding.

Symptoms of hypervitaminosis K may include:

• excessive bleeding, e.g. nosebleeds,
• hepatitis,
• pale skin, shortness of breath,
• feeling of heat and excessive sweating,
• impaired liver function.

The risk of hypervitaminosis K is limited to excessive intake of supplements or pharmaceutical preparations. The tolerable upper intake level (UL) for vitamin K has not been officially established.

6. Hypervitaminosis of group B vitamins

The B-group vitamins include: B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B9 (folic acid), and B12 (cobalamin). These are water-soluble vitamins, so their excess is usually excreted with urine. They do not accumulate in the body. This means that hypervitaminosis is rare, but it can occur. Particular caution is needed with vitamins B3, B6 and B9.

Of course, toxic effects from taking large doses of these vitamins can also occur and are specific to particular vitamins:

• Vitamin B1 (thiamine) – no documented cases of toxicity; the safe upper intake level according to EFSA is 40 mg. Exceeding this amount may cause gastrointestinal problems.
• Vitamin B2 (riboflavin) – toxicity has not been described, as excess riboflavin is efficiently excreted in urine.
• Vitamin B3 (niacin) – a characteristic symptom of excessive doses of vitamin B3 in supplements is skin redness, itching, nausea and vomiting. The tolerable upper intake level (UL) for niacin is 35 mg for adults.
• Vitamin B5 (pantothenic acid) – well excreted from the body in urine, very rarely causes complications even in high doses. Excessive amounts of this vitamin may cause diarrhoea and other gastrointestinal problems.
• Vitamin B6 (pyridoxine) – taken in excessive amounts may cause tingling and numbness, as well as peripheral neuropathy. Its toxicity is well documented. The tolerable upper intake level (UL) for B6 vitamin was lowered in 2023 by EFSA from 25 mg to 12 mg, with the maximum acceptable amount from supplements being 6 mg.
• Vitamin B7 (biotin) – generally well tolerated and excreted from the body; its toxicity, even in high doses, is not documented.
• Vitamin B9 (folic acid) – taking excessively high doses of folic acid can be dangerous due to masking B12 deficiency and leading to megaloblastic anaemia and neurological complications of B12 deficiency. The tolerable upper intake level (UL) is 1 mg (1000 μg) per day.
• Vitamin B12 (cobalamin) – excess is efficiently excreted in urine; toxicity is very rare. Nosebleeds, allergic reactions or dry skin may occur. The tolerable upper intake level (UL) for vitamin B12 has been set at 1000 µg for adults.

Important: This article discusses only vitamins and the issue of hypervitaminosis. There are also other ingredients in dietary supplements, such as minerals or antioxidants, which require caution.

15 rules for vitamin supplementation without risk:

1. Select vitamin supplementation according to individual needs – for example, taking into account blood tests, dietary exclusions or specific goals. Do not take supplements ‘blindly’.
2. Do not pick supplements off the shelf on the basis of ‘it might help with something, it certainly won’t do any harm’ – taking them without a clear plan may endanger your health.
3. Exercise particular caution when combining several multi-component supplements – it may turn out that you are taking the same ingredients, for example in supplements ‘for hair’ and ‘for concentration’, unknowingly exceeding safe doses.
4. If you take many supplements and/or medications, consult your doctor or pharmacist – there is a risk that their ingredients may accumulate or interact dangerously with each other.
5. Stick to the recommended doses and interpret them in context – pay attention to the Reference Intake (RI) stated on packaging in relation to your needs.
6. Never treat supplements as substitutes for a healthy diet and physical activity.
7. Remember that a supplement is not a medicine, and a medicine is not a supplement – take medicines according to your doctor’s recommendations.
8. Avoid high doses of supplements and do not trust people who suggest them.
9. Approach sources of information on supplements critically – use only those based on current scientific guidelines.
10. Remember that the food supplement market is relatively weakly regulated – the fact that a product is advertised by celebrities does not mean it is safe.
11. Check the doses of active substances and recommended servings – do not take any of your supplements ‘by eye’.
12. Store supplements in their original packaging – to avoid mistakes concerning their doses, which may lead to hypervitaminosis.
13. Be aware of synonyms in vitamin names – e.g. niacin and B3, cobalamin and B12. If the same substances appear in several preparations you take, include this when calculating a dose.
14. Pay attention to the units used in doses – they differ for various vitamins and their tolerable upper intake levels. Mistakes in unit conversions may lead to taking excessively high doses.
15. Remember that the tolerable upper intake level (UL) applies to all sources of a given vitamin, not only supplements.

^References:

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2. ^{Marins T. A., Galvão Tde F., Korkes F, Malerbi D. A., Ganc A. J., Korn D., Wagner J., Guerra J. C., Borges Filho W. M., Ferracini F. T., Korkes H., Vitamin D intoxication: case report, Einstein (Sao Paulo), 2014, Apr;12(2):242-4, doi: 10.1590/s1679-45082014rc2860. PMID: 25003934; PMCID: PMC4891171.}
3. ^{European Food Safety Authority, Tolerable upper intake levels for vitamins and minerals, EFSA, 2006. https://www.efsa.europa.eu/sites/default/files/efsa_rep/blobserver_assets/ndatolerableuil.pdf}
4. ^{Olson J. M., Ameer M. A., & Goyal A., Vitamin A Toxicity, StatPearls, StatPearls Publishing, 2023.}
5. ^{Asif A., & Farooq N.,Vitamin D Toxicity, StatPearls, StatPearls Publishing, 2023.}
6. ^{Roop J. K., Hypervitaminosis – An Emerging Pathological Condition, International Journal of Health Sciences & Research, 2018, 8(10), 280-288.}