Are they safe?

What does “the dose makes the poison” mean for supplements?

EFSA defines the tolerable upper intake level (UL) as the highest chronic daily total intake of a nutrient from all dietary sources that is not expected to pose a risk of adverse health effects in humans. ^[5] The UL is not for a single serving but for the habitual daily total. The values below are taken from EFSA’s adult column ^[5]; each covers a specific form and may differ from US (NIH/IOM) values.

The upper limit for the same nutrient may differ between organizations (for example, US and EU values for B6 diverge); the difference is explained with sources in the Vitamin B6 guide. For the difference between %NRV on a label and the UL, the guide How to read a label? can be consulted.

Why do fat-soluble vitamins need more attention?

According to the 2024 review by Andrès and colleagues, hypervitaminosis can occur when the body accumulates excessive amounts of vitamins, especially fat-soluble vitamins; causes listed include long-term use of high-dose vitamin supplements and vitamin-fortified foods and supplements. ^[6] The same review reports that the clinical signs of vitamin D hypervitaminosis are due to hypercalcemia (such as weakness, loss of appetite, weight loss, digestive problems, headache and vomiting), that in children excess can lead to hypercalcemia with brain and/or kidney damage, and that fetal malformation (aortic stenosis) has been reported in pregnant women. ^[6] The causes of vitamin D poisoning (excessive or inappropriate intake, manufacturing errors) and thresholds are given with sources in the Vitamin D excess guide. For vitamin A, TÜBER states that high-amount intake in pregnancy may increase the risk of anomalies of the heart, central nervous system and urinary tract in the baby. ^[7]

Which supplements show a liver injury signal?

A 2017 review based on a 2-day research symposium supported by AASLD and NIH reports that, according to research data in the US, liver injury linked to herbal and dietary supplements (HDS) accounts for 20% of hepatotoxicity cases. The main agents are anabolic steroids, green tea extract and multi-ingredient nutritional supplements. ^[2] According to the same review, anabolic steroids sold as bodybuilding supplements typically cause cholestatic injury that is prolonged but eventually resolves on its own, whereas green tea extract and many other products tend to cause injury resembling acute hepatitis. Most HDS-related cases come from multi-ingredient products and the responsible component is usually unknown or can only be suspected; the authors call for tighter regulation to ensure the ingredients and purity. ^[2]

Product-based liver data are given with sources in the relevant guides: Green tea (high-dose EGCG in supplements and liver enzymes), Ashwagandha (cases of liver injury and restriction in some countries), Curcumin (cases of liver injury reported with turmeric products) and Berberine (drug interactions and a pregnancy warning). TÜBER states that the misconception that plants are “completely harmless because they are natural” must be abandoned, that plants act through their many chemical compounds and that some may be beneficial and others harmful. ^[7]

Are there supplements with added drug ingredients?

Tucker and colleagues (California Department of Public Health) reviewed warnings from 2007–2016 in the FDA’s “Tainted Products Marketed as Dietary Supplements” database: unapproved drug ingredients were reported in 776 supplements covering 146 firms. Most products were marketed for sexual performance (353; 45.5%), weight loss (317; 40.9%) or muscle building (92; 11.9%). The most frequent ingredients were sildenafil in sexual performance products (166 of 353 products; 47.0%), sibutramine in weight-loss products (269 of 317 products; 84.9%) and synthetic steroids or steroid-like substances in muscle-building products (82 of 92 products; 89.1%). 157 of the products (20.2%) contained more than one unapproved substance; of 28 products named in 2 or 3 warnings, 19 (67.9%) had a new unapproved substance reported in the later warning. ^[3] This is an analysis of warning records; it does not show what percentage of products on the market carry this problem, and it is US data. The study received no funding and no conflicts of interest were reported; the erratum for the publication corrects a spelling error in two drug names, a figure key and one author’s affiliation, and does not change the numbers.

TÜBER reports that, where drug ingredients are detected in products during Ministry of Agriculture and Forestry inspections, administrative action is taken under the legislation and products containing drug ingredients are exposed through public announcements. ^[7] The same section also states that selling supplements with claims such as weight loss, height growth, sexual performance enhancement and quitting smoking is contrary to the legislation. ^[7]

Is there quality variation, contamination and doping risk?

Quality variation is also a safety topic. TÜBER states that applying good manufacturing practices (GMP) or HACCP in workplaces producing supplements is a legal requirement, but that not every supplement is of the same quality and that products that have not received Ministry approval can be marketed through various channels, above all the internet. ^[7]

In an athlete context, the risk of unlabeled substances has been measured in studies. Geyer and colleagues examined 634 non-hormonal nutritional supplements bought in 13 countries in 2000–2001; an anabolic androgenic steroid not stated on the label was detected in 94 (14.8%), and reliable data could not be obtained for 66 samples (10.4%) because of matrix effects. ^[4] This is a measurement more than twenty years old; it does not give today’s rate, but it shows that unlabeled substances are a measurable problem. Details on doping and third-party testing are in the Supplements for athletes guide.

Who needs extra caution?

• Pregnancy and breastfeeding: TÜBER states that the use of food supplements in pregnancy and breastfeeding must always be under physician supervision; it adds that supplements containing components other than nutrients may also have unwanted effects on maternal and infant health. ^[7]
• Children: According to TÜBER, no food supplement approval is issued for ages 0–2. In the Geller study, 21.2% of emergency department visits involved unsupervised children swallowing supplements. ^[1]
• Young adults and older adults: In the same study, 28.0% of visits were in young adults aged 20–34; weight-loss or energy products accounted for 71.8% of supplement-related adverse events involving palpitations, chest pain or tachycardia. Among those aged 65 and over, 37.6% of emergency department visits were related to choking, pill-related difficulty swallowing or sensation of a stuck pill, and in 83.1% of these micronutrients were involved. ^[1]
• Chronic illness and medicine use: TÜBER states that products used without a physician’s advice can adversely affect the course of the illness or cause drug interactions. ^[7]

How do drug interactions arise?

TÜBER gives concrete examples: vitamin K, high-dose vitamin E or glucosamine can interact with anticoagulants such as warfarin; calcium with tetracycline-class antibiotics and thyroxine; iron with tetracycline-class antibiotics, captopril and L-dopa. St. John’s wort (Hypericum perforatum) interacts with birth control pills, anesthetic drugs and some medicines used in depression, diabetes and cardiovascular diseases; more than one supplement can also interact with each other. ^[7] Full interaction lists and medicine–supplement time intervals are in a separate guide.

How does biotin affect blood tests?

The FDA reports that biotin, common in supplements, can markedly interfere with some laboratory tests and lead to wrong results, errors that may go unnoticed; the agency states that it continues to receive reports of falsely low results in troponin tests. ^[8] For this reason, products containing biotin (including hair-nail supplements and multivitamins) are among the information to be reported to the laboratory and the physician before a test. Details are in the Biotin guide.

Where are side effects reported in Türkiye?

TİTCK (Turkish Medicines and Medical Devices Agency) asks that suspected adverse reactions be reported to the Türkiye Pharmacovigilance Center (TÜFAM); the definition on the TÜFAM page covers a harmful and unintended response to a medicine. ^[9] In the Ministry of Agriculture and Forestry’s announcement on food supplements, it is stated that products not on the approved list or sold as supplements in violation of the legislation can be reported through the Güvenilir Gıda mobile app or the ALO 174 Food Hotline. ^[10] The scope of these two channels differs: one is for adverse drug reactions, the other for products that violate the legislation.

What are the red flags in marketing?

• Claims of weight loss or gain, height growth, sexual performance or quitting smoking: TÜBER states that selling supplements with such statements is contrary to legal regulations. ^[7]
• The approval number not being on the Ministry list: according to the Ministry, products not on the list are not considered approved. ^[10]
• Emphasis on “natural, therefore harmless”: TÜBER describes this as a misconception. ^[7]
• Statements implying “prevents or treats disease”: TÜBER states that the statement “Not a medicine. Not used to prevent or treat diseases.” is mandatory on supplement labels. ^[7]

The legal framework of health claims and the approval process are in the guide What are supplements?, and situations of need in the guide Do you need supplements?. This guide does not recommend a personal product or dose.