What is the Best Dose for B Vitamin Supplements?

Genes Mentioned

• MTHFR
• CBS
• COMT

Taking a good quality B vitamin supplement can have tremendous benefit. For example, pregnant women who supplement with folic acid during pregnancy. We know that people are not going to stop supplementing with B vitamins, nor do they necessarily need to, so our job here is to present the data in a useful way so you can make an educated decision when it comes to choosing a brand and a healthy B vitamin dose. Yes, B vitamins are a good thing, an essential thing to human health. However, the common thinking in supplement circles that because B vitamins are water soluble, they can be taken in larger and larger doses with no consequences, isn’t the whole story. In fact, at certain populations and at certain doses, supplementing with B vitamins seems to increase the risk for certain types of cancers. There are four main studies we’re going to reference here and I’ve summarized the findings in a giant table to the end of the post, but I’ll go through each one independently to describe the headline findings, and importantly the doses of B vitamins and groups assessed.

Studies linking B vitamin supplementation to cancer risk

B vitamin intake and cancer in women – 2008

The first article we’ll look at is this one from 2008,¹ which is the earliest paper we’ll look at, and which looks not only at folate supplementation, but also supplementation with thiamin, riboflavin and niacin. At the outset, the authors discuss the paradox of folate supplements. On the one hand, folate is necessary for the repair of DNA and methylation, but on the other hand, too much folate has been shown to fuel the growth of cancer cells.²  Simply put, the one carbon cycle, which contains many of those genes we mention above, relies on B vitamins to function correctly. We’ve covered what happens when there is a lack of activity, but in this instance the authors are interested in what happens if this cycle is supercharged by supplementing. The authors decided to investigate any effect using a large previously existing cohort generated as part of the “The Canadian National Breast Screening Study”. For this study the dietary intakes and cancer outcomes of 49,654 Canadian women between the ages of 40-59 were followed for five years between 1980 and 1985. Now this is a key point, as the study was retrospective and initially wasn’t interested in B vitamin or multivitamin intake, the authors have had to estimate vitamin intake based on the provided nutritional information and population averages, which is why the highest doses look a bit odd. Most importantly using this methodology the authors didn’t detect any significant association between their highest dose groups and cancer risk. None of the B vitamins were thought to be dangerous in this study. Score on for B vitamin supplements.

Cancer, Folic Acid and Vitamin B12 – 2009

Moving on to 2009, and a JAMA study, we see a different take on the study format. Rather than being retrospective, the authors of this study prospectively set out to assess cancer risk in relation to vitamin B dosing. In that way, this is a better study than the 2008 study. Doses and timing are much more accurate and so it should be easier to identify any associations. In this study, 6,837 patients from two Norwegian patient groups, with existing heart disease, were treated with certain B vitamins or a placebo between 1998 and 2005. Interestingly, the study authors identify a significant increase in cancer risk when patients supplemented with folic acid(0.8 mg/d) and vitamin B12 (0.4 mg/d) for 39 months, leading to an increased risk of cancer incidence (cancer being detected during the study period – hazard ratio 1.2) and cancer mortality (dying from cancer within the study period HR 1.38), in both instances lung cancer was especially increased. Quite a striking effect considering the doses and how closely these could mimic a daily supplementation regime. But it is important to remember that these individuals had a pre-existing diagnosis of heart disease and so this may not be representative of an otherwise healthy population. Nonetheless, doses of 0.8mg of folic acid and 0.4mg of B12 are very common in dietary supplements, so this study offers a real warning sign to those who mega dose B vitamin supplements over a long period of time.

B vitamins, methionine and risk of lung cancer

When you see lung cancer the immediate thought is smoking, so it’s no surprise that based on the above study two quite similar papers came out in 2012 and 2013. The obvious question is what do B vitamins do to those who are already at risk of cancer? Does supplementing with B vitamins “turn on” the cancer?  Both of these studies approached the question in the same way, using a retrospective study to investigate an already existing data set. In the case of the first paper this was the “The Melbourne Collaborative Cohort Study” which followed 41,514 men and women between 40-69 between 1990-1994 (and beyond for many individuals), and in the latter case “The Shanghai Women’s Health Study” which followed 74,941 women aged between 40 and 70. As with the first study, both of these studies relied on using retrospective data points, and as the main focus of the study wasn’t B vitamins, individuals were group based on their general nutritional intake, and approximate B vitamin values calculated. Interestingly, in both studies the increase in cancer risk in individuals with a high vitamin B intake wasn’t observed. BUT, the high dose groups in these studies are most likely below the levels of B12 used in the 2009 JAMA study. For example in the JAMA study patients received 0.4mg/d of vitamin B12 whereas the dose was 0.04mg/d in the 2013 Chinese study. Also both of these studies reported a protective effect for vitamin B2 in smokers, or those who had previously smoked, reducing their risk of developing lung cancer.

Long-Term B Vitamin Use and Lung Cancer Risk – 2017

Performing clinical trials is expensive and very time consuming so retrospective studies applied to existing data sets are a vital part of research. But as you’ve seen above, trying to calculate B vitamin intake after the event is not the most accurate way of addressing things. Enter this 2017 study which looked at 77,118  men and women between the ages of 50 and 76 with defined vitamin B intakes over 10 years, these defined intakes were taken as either multivitamins or individual dosings and a huge raft other metrics were also recorded. Their take home findings were pretty startling:

• In women high dose vitamin B6, B12 or folic acid was not associated with an increased cancer risk.
• In men both vitamin B6 (20 mg/d – HR 1.82) and vitamin B12 (0.55 mg/d – HR 1.98) were associated with an increased lung cancer risk.
• For current smokers this risk was even worse (B6 HR 2.93 and B12 HR 3.71).
• This was only observed for single supplements not multivitamins.

Quite a lot to digest there, but there are some interesting things we can draw out from these findings. Firstly, the doses used are higher than in the retrospective studies, and the lower doses used in these studies did not report any significant association. So only the highest doses of B6 and B12 had any association. Secondly, smoking while on these high doses seems to be a big risk, the combined HR from B6 and B12 should be concerning for smokers.

Is vitamin B2 protective?

Finally, the lack of effect from multivitamins is very interesting. One possible hypothesis is that the presence of vitamin B2, which other studies showed was protective, can block the increased cancer risk of B6 and B12 at high doses. Unfortunately, this study didn’t assess vitamin B2 alone so we can’t say for sure but the hypothesis fits with the data available so far.

Evaluating B Vitamin Supplements

The obvious concern here is dose. We want doses of folic acid of less than 0.8mg, and B12 at less than 0.4mg. It’s also preferable to have B6 at low doses, both because of the cancer issue, as well as because of some data that indicates B6 can cause nerve damage at higher doses. For example, when I have experimented with 50mg doses of B6 as a way to stimulate diamine oxidase production to clear excess histamine, I have experienced tingling in mu feet, which is definitely no bueno. We’ve also theorized that pairing these B vitamins with B2, or other antioxidants, could have a protective effect, so the data seems to indicate that supplementing with B vitamins is safer as part of a multivitamin. Ok, so armed with that knowledge, let’s explore some of the options out there for supplementing with B vitamins and see if we can identify some good products.

Vitamin B12 dosing

To begin, Vitamin B12 seems to be the most popular B vitamin to supplement with, and the market has responded with mega dose supplements everywhere. These supplements usually list doses in terms of micrograms. You’ll most commonly see 1,000 and 5,000 mcg doses. This converts to 1 mg and 5 mg respectively. Tying this back into the JAMA study, we see that a 1 mg dose is more than double the 0.4 mg dose of B12 that was associated with an increased risk of cancer in the Norwegian population. 1 mg of B12 represents 16,667% of your daily B12 intake. So, in the world of B12 supplements, we want a product that offers methylcobalamin (the quality form of B12) and a dose of 500 mcg or less. Good luck. Most of the products on the market are made with at least 1,000 mcg. This B12 product by Nature’s Way is made with only 500 mcg, but Nature’s Way uses cyanocobalamin, which is cheap B12 that we want to avoid. Then you have products like this one from Jarrow, which uses 5000 mcg of methylcobalamin, which is way too large of a dose for regular use. Now let’s turn our attention to B complex products. That’s probably where we want to play anyway because of the potential protective effect of B2.

B Complex supplements with more conservative doses

It is important to keep in mind that you may not need a B vitamin supplement at all. Although many who have MTHFR mutations feel better on a methyl folate supplement, side effects are also common. be sure to discuss the pros and cons of taking B vitamins with your doctor before starting with any of these products.

Pure Encapsulations B Complex Plus

Pure Encapsulations B Complex Plus is one of my favorites. It has a relatively conservative dose of a high quality B12 (methylcobalamin) at 400 mcg, and also offers 400 mcg of folate (methylfolate), which cuts the 0.8 mg dose of folic acid from the JAMA study in half. Pure also adds B2 to the formula which, based on the data, we have theorized could be protective.

Thorne Research Stress B Complex

However, as much as we like the Pure B Complex, Thorne Research makes my favorite B complex supplement because the dosing is so conservative, even more so than the Pure product. If you want to “push the envelope” in a safe way, Pure could be a good option, but if you want to supplement with B vitamins and play it very safe, I would opt for Thorne. The B12 dose (methylcobalamin) is only 100 mcg, which I love, and the folate dose is 334 mcg, again well below the dose used in the JAMA study. Thorne adds B2 to the formula, but the one thing I don’t like about the Thorne product is the high dose of B6 which comes in at 28.4 mg. This is a very large dose that I would not take for extended periods of time. The Thorne B complex, like most B complex supplements, should be cycled on and off.

Take home message

The take home message from all these studies is quite clear. High doses of B6 and B12 have a strong cancer promoting effect, especially in men, with male smokers being at the highest risk. This risk isn’t seen with lower doses, or in multivitamins (potentially because of the protective B2 effect). So check your supplement doses! While these vitamins are key in the one carbon cycle, and may be helping with certain SNPs it is very possible that you could get away with a much lower dose. For those thinking of starting B vitamin supplements to help with their SNPs we would always recommend starting at lower doses (1/3 of a capsule or lower) and keeping a diary to record what effect these have, rather than jumping in with the maximum dose. More is not always, or even usually, better when it comes to supplements. See John’s post – Could Your Supplements be Making You Sick?

B Vitamin and Cancer Risk Diagram

We put together this visual to chart the various studies that have evaluated B vitamin supplements and cancer risk.