B vitamins are essential for metabolism and overall health, acting as coenzymes in many cellular processes, including those in the brain and nervous system. Lack of B vitamins can disrupt metabolic pathways, affecting the processing of amino acids, glucose, and fatty acids.
Since B vitamins are coenzymes for energy metabolism, to ensure adequate intake some dietary supplements include very high doses of B vitamins with some B vitamins provided in a daily supplement over hundreds of folds of the recommended daily intake level. Even though B vitamins are water-soluble, the surplus of B vitamins would be excreted rather than stored, so the toxicity is rare compared to fat-soluble vitamins. However, studies have reported that overdoses of B vitamins may have adverse effects.
A review (1) summarized the effect of B vitamins on the immune system and the negative effects of overdoses as follows:
Positive effects of vitamin B2 (riboflavin):
Riboflavin supplementation is recommended for its anti-inflammatory effects in various diseases like angular cheilitis, glossitis, sepsis, cataracts, and migraine headaches. It suppresses inflammatory cytokines such as NO, IL-1, IL-1β, IL-6, and IFN-γ. Riboflavin optimization helps combat bacterial infections caused by Staphylococcus aureus and Listeria monocytogenes by controlling ROS levels. In animal experiments, riboflavin prevented lung metastases from melanoma.
Negative effects of riboflavin overdose:
Excessive riboflavin (vitamin B2) intake, especially when taken regularly, can react with light, leading to cell failures. Free riboflavin becomes a potent oxidant due to its light-reactive properties, generating damaging peroxides and other reactive oxygen species.
High-dose riboflavin supplementation significantly boosts the spread of cancer cells through proliferation, invasion, and migration. Elevated levels of riboflavin in the blood are associated with a significantly increased risk of colorectal cancer.
Positive effects of Vitamin B3 (niacin):
Vitamin B3 effectively fights reactive oxygen species. It is used to lower lipid levels. It can raise the good cholesterol HDL-cholesterol levels and lower bad cholesterol LDL-cholesterol and triglyceride concentrations. It plays a protective role against cognitive decline in Alzheimer's disease. Vitamin B3 plays a role in nourishing colon cells and reducing inflammation in the intestines. Insufficient levels are linked to inflammatory bowel disorders.
Negative effects of niacin overdose:
Niacin can result in more severe side effects when taken in higher dosages. These include multiple organ failure, hypotension, and hepatotoxicity. In high niacin doses, isolated cases of acute hepatitis have been reported. Ingesting around 3 g per day is linked to liver damage, while just 30 mg per day is enough to cause facial flushing. Long-term niacin feeding in mice for 15 weeks resulted in insulin resistance.
Positive effects of Vitamin B5 (pantothenic acid):
Vitamin B5 is absorbed in the colon and bloodstream, mainly as Coenzyme A, crucial for cellular functions. Vitamin B5 plays a crucial role in managing oxidative stress, cellular adhesion, and effectiveness against polynuclear organisms. It stimulates the production of antibacterial cytokines in both isolated macrophages and infected animals. It may aid the inflammatory process by increasing CoA levels and promoting the synthesis of glutathione (GSH), which reduces oxidative stress. It has been used as a treatment for patients at low to moderate risk of cardiovascular disease, reducing cholesterol levels and fractions. It enhances the body's immune response to fight against cancer.
Vitamin B5 is also used in treating hyperlipidemia due to its role in triglyceride synthesis and lipoprotein metabolism. However, studies have conflicting results regarding its effectiveness, with pantethine showing some decrease in blood lipid concentrations while pantothenic acid alone doesn't seem to have a similar effect.
Negative effects of vitamin B5 overdose:
Overdose of vitamin B5 causes conditions like semi-coma, Reye-like syndrome, and encephalopathy （The condition commonly causes an altered mental state including memory loss or personality changes). It is linked to digestive problems and liver issues in older individuals. Increased intake is connected to more genome damage, indicating a higher cancer risk.
Positive effects of Vitamin B6 (pyridoxine):
Vitamin B6 is absorbed in the small intestine, with bacterial production also contributing. No known intestinal transporter exists for vitamin B6 in mammals. Vitamin B6 levels tend to increase after multivitamin supplementation, with high levels observed in those consuming energy drinks regularly.
Vitamin B6 can prevent the release of ROS (reactive oxygen species). It might lower the risk of colorectal cancer. It has been used to treat various conditions including type 2 diabetes, kidney disease, high blood pressure, and heart problems.
Negative effects of vitamin B6 overdose:
High vitamin B6 concentrations (>2000 mg per day) had been shown to harm the dorsal root ganglia. Sensory symptoms were experienced by 80% of individuals at doses around 70 ng/mL. Metabolites of pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, cause nerve damage, but how this happens is not fully understood.
In a dose of 17 ± 92 mg/day for 2.9 ± 1.9 years, bone pains, hyperesthesia, and numbness were seen in women. The time of administration was a significant factor in all these adverse effects, and it is an essential factor that determines the toxicity of this vitamin. As vitamin B6 is a water-soluble vitamin, large doses should not give rise to problems, but the toxicity is related to the fact that its metabolites interact with certain proteins, and the half-life of this vitamin metabolite is quite long (~15–20 days). PLP has been linked in research studies to a higher risk of lung cancer and other cancers.
Positive effect of Vitamin B12 (cobalamin):
Vitamin B12 is synthesized by certain microorganisms and absorbed with the help of the intrinsic factor in the ileum. Vitamin B12 is often provided in doses exceeding daily recommendations, but toxicity is rare due to the body's inability to store excess amounts. However, high doses have been associated with symptoms like anxiety, palpitations, facial redness, and headaches in some cases.
In children up to 6 years old, it can lower blood pressure. It is linked to better cognitive function in older adults.
Negative effects of vitamin B12 overdose:
Eating more vitamin B12 was associated with a higher chance of getting lung cancer. Having consistently high levels of vitamin B12 was connected to a higher occurrence of solid cancers.
B vitamins have various effects on the immune system and can have negative effects when overdosed. Examples include that riboflavin supplementation can be beneficial against inflammatory diseases but may promote cancer cell spread at high doses. Niacin has benefits for cholesterol levels but can cause liver damage in high doses. Similarly, vitamins B5, B6, and B12 have both beneficial effects on immune function, and harmful effects when overdosed.
Dietary supplements on the market come in various doses and formulations. It is important to know that dietary supplements in the United States are not regulated by the Food and Drug Administration, thus manufacturers can make claims that may not be scientifically approved. For dietary supplements, taking very high doses does not necessarily lead to good health. The most probable cause of people consuming vitamins above the safe suggested upper limit is the fact that these supplements are offered over the counter. People frequently are not aware of the risk caused by large doses of vitamins such as those discussed about B vitamins. Overdosing may result in clinically noticeable symptoms, for example, in a case report a patient with peripheral neuropathy was admitted to a hospital and found that he consumed vitamin B-complex supplements at a dose of fifty times the daily recommended dosage for ten years. Hope that this blog can serve to caution people who are long-term users of mega-doses of B vitamins.
Reference:
1. Munteanu C, Schwartz B. B Vitamins, Glucoronolactone and the Immune System: Bioavailability, Doses and Efficiency. Nutrients. 2023 Dec 20;16(1):24. doi: 10.3390/nu16010024. PMID: 38201854; PMCID: PMC10780850.
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