Index
Recent evidence has linked them to an increased risk of lung cancer in men, especially smokers.
B vitamins are common ingredients in multivitamins , of course, but also in energy enhancers like energy drinks.
But while they are best known for their role in energy metabolism, they may play a role in cancer biology through participation in the metabolism of a carbon and therefore DNA synthesis and methylation reactions .
This hypothesis was confirmed in 2015 when a newspaper article caused a stir by reporting that nicotinamide (a form of vitamin B 3 also known as niacinamide) could reduce the rate of new non-melanoma skin cancers.
The B vitamins had earned a “anti-cancer” reputation.
However, it was only one study showing that one form of vitamin B 3 could reduce the rate of one type of skin cancer; it did not exclude the possibility that some B vitamins might make at least some cancers worse.
To look for other possible connections between vitamin B supplementation and cancer, experts conducted a large observational study.
Since its publication in an oncology journal in 2017, this study has taken the supplement world by storm, linking vitamins B 6 and B 12 each to a 30-40% increase in overall risk of lung cancer in mens.
Study design
To look for possible connections between vitamin B supplements and lung cancer , the researchers analyzed data from all 77,000 participants in a previous study.
The study itself was designed to look for possible associations between cancer risk and vitamin, mineral, and non-vitamin / mineral supplementation.
The researchers chose to focus on vitamins B 6, B 12, and B 9, which play an important role in one-carbon pathways and are therefore more likely to affect carcinogenesis.
Study participants, aged 50-76 years at the start of the study, were classified into five groups based on their average daily dose of supplemental B vitamins over the past 10 years.
Then, statistical techniques were used to adjust for confounding factors, such as age, education, body size, and family history of lung cancer.
What was the results?
When the data were stratified by sex, vitamins B 6 and B 12 as individual supplements were shown to increase the risk of lung cancer by 30-40% in men (but not in women).
The highest risk was found among men with the highest average daily dose of B 6 (> 20 mg / day was associated with an 82% higher risk) and B 12 (> 55 mcg / day was associated with a 98% higher risk) the ten years prior to the study.
When the data were stratified by smoking, an increased risk was associated with smoking.
Smokers who had supplemented with high amounts of B 6 had almost three times the risk of developing lung cancer, and those who had supplemented with high amounts of B 12 had more than three times the risk.
The study found no association between supplementation and increased risk in ex-smokers or recent smokers.
As for those who never smoke, the paper states that “they were excluded from the stratified analysis for smoking due to the low number of participants with incidental lung cancer in that group.”
The study showed that long-term supplementation with vitamins B 6 or B 12 increased the risk of lung cancer in current male smokers, especially those who supplemented with high doses of either vitamin.
What is the mechanism?
Chemical groups with one carbon lack stability, so they must bind to larger molecules in a process called one-carbon metabolism.
Vitamins B 6, B 9, and B 12 play an important role in one-carbon metabolism, which in turn plays a crucial role in nucleotide synthesis and methylation reactions.
The nucleus of each of your cells contains your complete DNA. The genetic blueprint for every protein in your body is encoded in your DNA.
How can cells maintain a unique identity? By reading only certain parts of your DNA, so that only the appropriate genes are activated at the appropriate time.
For that purpose, sections of your DNA can be “tagged” with methyl groups that prevent the expression of nearby genes. This type of epigenetic imprinting is essential for keeping cells normal, healthy, and well-behaved.
When the process becomes dysfunctional, the wrong genes can be turned on at the wrong time, which can lead to uncontrolled cell growth – cancer.
So how do high amounts of B 6 or B 12 increase cancer risk? We could find some clues in a recent study on DNA methylation, which found that two years of supplementation with 400 mcg of B 9 and 500 mcg of B 12 modified DNA methylation.
Therefore, the increased risk of cancer seen in the study could be caused, in part, by changes in DNA methylation from long-term B-vitamin supplements.
Another curious finding from the study was that only men saw an increased risk of cancer from supplementation with B 6 or B 12.
Not women. We know that androgens regulate some of the enzymes involved in the metabolism of a carbon, which could explain the difference.
Androgens and vitamins B 6, B 9, and B 12 interact to play a role in DNA methylation.
Since DNA methylation partly determines which genes are turned on (or not) at any given time, this could explain the link between long-term B vitamin supplementation and cancer risk in men.
What does this study mean?
The study was not designed to show causation, but it did reveal a strong correlation between increased risk of lung cancer and long-term supplementation with B 6 / B 12, especially at high doses and among smokers.
There are several ways that B vitamins can interact with cancer metabolism; More research is needed to determine the exact mechanisms at work. In the meantime, we have three points left:
Smoking, as you know, causes lung cancer. If you smoke, stop. If you can’t stop, avoid supplementing with B vitamins for a long time, especially if you are a man.
Long-term vitamin B supplementation appears to increase cancer risk in male smokers, possibly enhancing carcinogenesis in precancerous cells in response to carcinogens in cigarette smoke.
This would explain why only current smokers, not previous or recent smokers, seem affected.
The effect of B vitamins in non-smokers is still uncertain. In this study, the sample sizes for non-smokers were too small to assess associations accurately.
Although observational studies cannot show causality, the associations between B vitamins and cancer risk found in this study raise an important point, which is that high-dose, long-term consumption of any supplement can interact with your biochemistry. unexpected ways.
Exceeding recommended and recommended doses of even the healthiest micronutrients may not be safe.
Q&A with lead study author Dr. Theodore Brasky
When this study was published, their discovery that vitamin B supplements increased cancer risk in men generated a lot of pressure.
But isn’t there some nuance to that finding, especially regarding smoking habits? What final take-home message can be gleaned from the data?
The nuance centers around the general idea that once you start clipping the data, you lose precision. In epidemiology, our best estimates come from data that reflects the largest sample sizes.
Our most cited finding was that long-term, high-dose vitamin B 6 and high-dose long-term vitamin B 12 were each associated with a doubling of lung cancer risk in men.
This is a completely true representation of our results.
However, when we delved deeper and lost some precision, we found that this double increase in risk was an average across different groups of men, some with no increased risk (men who had never smoked or had quit at the time).
Here the scientist is left with two possibilities
Is the actual finding (a) based on the largest sample size with more accurate data? Men who use these supplements have twice the risk of lung cancer than men who do not use these supplements.
And (b) based on the subgroups within men with less precise results?
Men who currently smoke and use these supplements have three to four times the risk of lung cancer than men who currently smoke and do not use these supplements. For me, the takeaway message is the last one.
The dosage, frequency, and duration of supplementation are all important from a biological point of view.
How were these factors taken into account in the design of the study questionnaire? What were the pros and cons of different ways of using those factors (and others) to identify significant associations with lung cancer risk?
Simply put, we have a number of options.
We could separately analyze the frequency of use of a given supplement (that is, days per week), the duration of use (that is, the number of years in the last 10 [our questionnaire only asked about the last 10 years of use] ) and the most common dose used, or we could combine those data.
The separate analysis of a single aspect eliminates the influence of the other two, which, in my opinion, is not ideal. Combining the data provides two additional options.
We could determine a cumulative dose in the last 10 years or an average daily dose in the last 10 years.
We chose the latter because it is easier to understand and because it allowed us to compare the risks with what might be expected from intakes at the level of a multivitamin taken daily for the same amount of time.
However, the downside to this option, which I contend is still better than the alternatives, is that the 10-year daily dose calculation equates to short-term high-dose intakes with long-term lower dose intakes.
The highest category of B 12 supplement intake, for example, was> 55 mcg / day. This is> 55 mcg taken daily, on average, over 10 years.
For some people, it may have been about that amount daily for 10 years, but for most it was short-term use at higher doses that averaged up to this level.
Therefore,> 55 mcg should not be interpreted as the actual dose that could confer risk. In fact, most B 12 supplements are sold at much higher doses.
A standard pill from a bottle at the supermarket can contain between 500 and 2,000 mcg, with instructions that it should be taken daily. This is the reason why the comparison with what could be consumed from a multivitamin (100% RDA) is useful.
Although the question “Do vitamin B supplements increase the risk of cancer?” It’s simple, extracting another solid answer from a given study population is another matter. Epidemiologists like you are experts at identifying risk associations within large study populations.
At the other end of the spectrum, basic scientists like myself tend to use defined experimental models to identify important cellular / molecular controls that drive disease processes.
Could you comment on how epidemiological studies and basic science (i.e. laboratory research) fit into the bigger picture of biomedical science? Do you feel that they complement each other?
Epidemiologists cite rodent studies because in these experiments many of the variables can be controlled. The animals are very similar genetically, they are all fed the same diet (unless it is a nutrition study), managed in the same way, etc.
In addition, we can conduct some tests on animals that are considered immoral in humans, exposing rodents to smoking tobacco, for example. We often view the results of these studies as hypothesis generators because, after all, the animal is a model for the human.
People, in fact, do not have hair or tails, and we are much more genetically diverse than rodents bred for disease models.
In some cases, animal models are better approximations than others. Mice have heat cycles rather than menstrual cycles, so some similarities for reproductive cancers are obscured by physiology here.
Similarly, the prostate gland of a mouse is structured differently from that of a man; again, models.
The idea is the same for work involving cells in Petri dishes, although the contrast is more stark. On the other hand, from what my colleagues in these fields tell me, epidemiological research, which is predominantly carried out observationally, is seen as hypothesis generation.
That we all work together towards the same goal is the important thing.
Although we definitely give each other pain, epidemiologists appreciate basic scientists for their explanation of biological mechanisms, and (I suppose) basic scientists appreciate epidemiologists for their findings that need biological explanation.
