Researchers studied how two B vitamins—folic acid and vitamin B12—affect liver cancer cells in the lab. They found that having too much folic acid combined with too little vitamin B12 may make cancer cells more aggressive and harder to kill. The study suggests that keeping these two vitamins in proper balance in your body might be important for preventing cancer growth. While this is early laboratory research, it opens new questions about whether vitamin balance could play a role in liver cancer prevention and treatment.

The Quick Take

  • What they studied: How different amounts of folic acid and vitamin B12 affect liver cancer cell behavior, including whether cells can move, invade other areas, and survive
  • Who participated: Laboratory-grown liver cancer cells (HepG2 cells) exposed to five different combinations of folic acid and vitamin B12 levels—from too little to too much of each vitamin
  • Key finding: Cancer cells exposed to high folic acid with low vitamin B12 became more aggressive, moved more easily, and were harder to kill. Cells with balanced vitamin levels or low folic acid showed less aggressive behavior
  • What it means for you: This suggests that maintaining proper B vitamin balance may be important for health, though this is early lab research. Don’t change your vitamin intake based on this study alone—talk to your doctor about your individual vitamin needs

The Research Details

Scientists grew liver cancer cells in laboratory dishes and exposed them to five different combinations of folic acid and vitamin B12 levels. One group had normal amounts of both vitamins, while other groups had too much of one and too little of the other, or too much of both. They then tested how these vitamin combinations affected cancer cell behavior by measuring whether cells could move around, invade other areas, form clusters (called spheres), and whether they died or survived.

This type of study is called an ‘in vitro’ or laboratory study, meaning it happens in a dish rather than in living bodies. Scientists use these studies to understand basic biological processes before testing in animals or humans. The researchers chose five specific vitamin combinations to see if balance between the two vitamins mattered more than just having enough of each one individually.

The study measured several ‘cancer hallmarks’—characteristics that make cancer cells dangerous, like their ability to move, invade, and survive. By testing different vitamin combinations, the researchers could see which balance (or imbalance) made cancer cells behave most aggressively.

This research matters because it tests a new idea: that it’s not just about having enough of each vitamin, but about having the right balance between them. Previous studies looked at folic acid and vitamin B12 separately, but this study examined them together. This approach is important because these two vitamins work together in your body through a process called ‘one-carbon metabolism,’ which affects how cells grow and divide. Understanding this balance could eventually help doctors think about vitamin recommendations differently.

This is laboratory research using cancer cells grown in dishes, which is a good starting point for understanding how vitamins affect cancer cells. However, cancer cells in a dish don’t behave exactly like cancer in a living person. The study doesn’t tell us what happens in human bodies or whether these findings apply to people. The researchers used standard scientific methods and tested multiple vitamin combinations, which strengthens the findings. However, because this is early-stage research, results need to be confirmed in animal studies and eventually human studies before drawing firm conclusions about health recommendations.

What the Results Show

When cancer cells were exposed to high folic acid combined with low vitamin B12, they became significantly more aggressive. These cells moved around more easily (increased migration) and formed more sphere-like clusters, which are signs that cancer cells may be more dangerous and harder to treat.

Interestingly, when folic acid was low and vitamin B12 was high, cancer cells actually became less aggressive in some ways—they moved less and more of them died. This suggests that the imbalance in one direction (too much folic acid, too little B12) is worse than the opposite imbalance.

The study also found that cells with high folic acid formed more spheres (clusters of cells), which is concerning because these sphere-forming cells are often more resistant to treatment and more likely to spread cancer. This effect happened whether vitamin B12 was normal, low, or high—as long as folic acid was high.

When both vitamins were at normal levels, cancer cells behaved less aggressively overall, suggesting that balance between the two vitamins is protective.

The research revealed that the relationship between these vitamins and cancer cell behavior is complex. Having too much folic acid seemed to be the main driver of aggressive cancer cell behavior, but the effect was worst when combined with low vitamin B12. The study also showed that cells with the worst imbalance (high folic acid, low B12) had fewer living cells overall but the ones that survived were more aggressive—suggesting these conditions select for the toughest, hardest-to-kill cancer cells. Additionally, the formation of cancer stem cells (special cells that can create new tumors) appeared to be promoted by the high folic acid and low B12 combination.

Earlier research has shown that folic acid and vitamin B12 are connected to cancer risk, but most studies looked at each vitamin separately. This study is novel because it specifically examines what happens when the balance between them is off. Previous population studies in patients suggested that vitamin imbalances were associated with more aggressive liver cancer, but this is the first laboratory study to test the mechanism—how and why this imbalance makes cancer cells behave differently. The findings support and help explain what those earlier patient studies observed.

This study has important limitations to understand. First, it’s laboratory research using cancer cells in dishes, not actual cancer in living people. Cancer cells in a dish don’t experience the complex environment of a human body, including the immune system, blood flow, and other organs that affect cancer behavior. Second, the study doesn’t tell us what vitamin levels are actually found in people with liver cancer or whether these lab-tested levels match what happens in real bodies. Third, the study doesn’t prove that changing vitamin intake would prevent or treat cancer in people. Finally, the sample size and specific details about the cell culture conditions weren’t fully specified, which makes it harder to assess how reliable these findings might be.

The Bottom Line

Based on this early laboratory research, there is NOT yet enough evidence to recommend changing your B vitamin intake to prevent or treat liver cancer. This is preliminary research that needs confirmation in animal studies and human trials. If you have concerns about liver cancer risk or your vitamin levels, talk to your doctor about appropriate screening and supplementation for your individual situation. General recommendations to maintain adequate B vitamins through a balanced diet (including leafy greens, eggs, meat, and fortified grains) remain appropriate.

This research is most relevant to scientists studying cancer and vitamin metabolism, and to people at high risk for liver cancer (those with hepatitis B or C, cirrhosis, or family history). It may eventually be relevant to people considering B vitamin supplementation, but that time hasn’t come yet. This research should NOT be used to self-treat or change supplementation without medical guidance. People currently taking B vitamin supplements should continue their current regimen unless advised otherwise by their doctor.

This is very early-stage research. If these findings are confirmed in animal studies (1-2 years), and then in human studies (3-5+ years), it could eventually lead to new recommendations about B vitamin balance. Don’t expect practical health changes from this research for at least 5-10 years, if the findings hold up through further testing.

Want to Apply This Research?

  • Track daily B vitamin intake from food sources (servings of leafy greens, eggs, meat, fortified cereals) and any supplements taken, noting the amounts of folic acid and B12. This creates a baseline to discuss with your doctor if you have liver cancer risk factors
  • If you’re at risk for liver cancer, work with your doctor to ensure you’re getting adequate (but not excessive) B vitamins through food rather than high-dose supplements. Use the app to log B-vitamin-rich foods and discuss your intake with your healthcare provider at regular checkups
  • For people at liver cancer risk, monitor your B vitamin intake monthly and review with your doctor annually. If you take supplements, keep records of doses and discuss whether they’re still appropriate based on your individual health status and any new research

This research is preliminary laboratory work and does NOT provide medical advice for preventing or treating liver cancer. The findings have not been tested in humans and may not apply to real-world situations. Do not change your vitamin intake or supplementation based on this study without consulting your doctor. If you have risk factors for liver cancer (hepatitis B or C, cirrhosis, family history) or concerns about your vitamin levels, speak with a healthcare provider about appropriate screening and personalized recommendations. This article is for educational purposes only and should not replace professional medical advice.