How to navigate the confusing world of vitamins

By Dr Ross Walker

A study on vitamins was published in the Journal of the American Medical Association, Network Open on June 26, 2024 from the National Cancer Institute. It reviewed 390,124 US adults over a 20 year follow period from three prospective US cohorts. The people in the study were generally healthy with no history of cancer or other chronic diseases.

The bottom line from the study was that there was no difference in death whether did or didn’t take a multivitamin. Let me make the point that this was not a randomised control trial. Some of the points made by the authors were that people who consumed multivitamins also had a healthy lifestyle. They then stated that sicker patients may have taken multivitamins to mitigate illness.

In my view, neither of these contradictory statements make any sense. On the one hand they are suggesting that taking a multivitamin is purely a marker for people who are practice a healthy lifestyle and thus they are healthier. Then they state that sicker patients take multivitamins believing it will make them healthier?

So does this settle the conservative medical argument that all vitamins do is give you expensive urine? Or is there another side to the story?

Available evidence

A few months ago more data was released from the COSMOS analysis. AKA the Cocoa supplementation and Multivitamins Outcome study, published in the American Journal of Clinical Nutrition. There were three separate components to the COSMOS trial and they were combined in a metanalysis. This study included more than 5000 patients over the age of 60. It showed that those who took a multivitamin for at least two years had a significant benefit in terms of cognitive ageing and improved memory.

Reduction in progression of dementia

Two studies were performed by Professor David Smith’s group at Oxford University. They were known as the Optima trial and the VitaCog study. They looked at the benefits of folic acid, B12 and B6 in people with mild cognitive impairment. Both studies used 800 µg of folic acid, 500-1000 µg of B12 and 20 mg of B6. This demonstrated a 30% reduction in progression to dementia over a three year period using neuro cognitive testing and brain MRI. The VitaCog study in particular showed that these benefits were only present in those people with high levels of Omega 3 in their bloodstream.

Is long-term use a factor?

The long-term analysis of the Nurses Health study and the Male Physicians trial from Boston. It revealed that taking multivitamins up to 10 years derived no benefit. When the data was analysed at 10 years in the Male component of the trial there was an 8% reduction in cataracts and common cancers.

At 15 years in the females there was a 75% reduction in bowel cancer, a 25% reduction in breast cancer and a 23% reduction in cardiovascular disease in those taking a daily multivitamin. When the data was analysed from the Male component of the study at 20 years, there was a 44% reduction in those doctors who took a multivitamin daily for 20 years.

Interestingly, however, the Iowa Women’s study which involved around 20,000 women over 20 year period showed no benefits when multivitamins were given on a daily basis.

Folic acid and reduction in strokes

Another study from China known as CSPTT of 20,702 people followed up for three years in a randomised, controlled trial of the blood pressure drug Enalapril with placebo or Enalapril with folic acid 5 mg daily. It demonstrated a significant reduction in strokes in those people in the Enalapril and folic acid group. However, it was only in people who did not have a genetic mutation in the MTHFR gene.

Folic acid and prostate cancer

Finally, a study of 643 men, average age 57, were given folic acid 1mg daily, as part of an Aspirin and Colonic polyp trial. It demonstrated that over a 10 year period there were three times the rate of prostate cancer in those taking the daily folic acid.

How is it all so varied?

The MTHFR gene

All of this data is incredibly contradictory and confusing but I believe the answer is very straightforward. It all revolves around a very common genetic abnormality involving the MTHFR gene. 50% of the population have a mutation in this particular gene which is a vital gene regulating Epigenetics through 1-carbon metabolism. 1-Carbon metabolism is central to the regulation of DNA, RNA and protein metabolism.

If people with this genetic abnormality, i.e. 50% of the population, are given standard folic acid, this is not being metabolised properly. As a consequence, unmetabolised folic acid rises in the bloodstream.

What are the consequences?

This has a direct deleterious effect on immunity and may lead to an increased risk for cancer in older people. This is a particular problem in those older people with the very common low B12 level. This may also precipitate cognitive decline in this group. If someone is taking extra B6 or has a genetic abnormality involving B6 metabolism they may also develop a peripheral neuropathy when standard folic acid is given to people with a low B12 level, as seen in pernicious anaemia or in Vegans.

The reason why all of the above studies are so contradictory was there was no separation for people with and without the MTHFR abnormality. This is with the exception of the CSPTT Chinese study.

Is there a solution?

Fortunately over the past few years a fourth-generation folic acid has been available on the market. This is known as 5 Methyl tetrahydrofolate, in a glucosamine salt. This product bypasses the gene abnormality and in my view should be the only folic acid used in all multivitamins. It will then cover the 50% of people born with the MTHFR gene abnormality.

Unfortunately, up until now, long-term studies using multivitamins that have this new and improved fourth generation folic acid have not been performed. However, their effectiveness and safety has been studied extensively. Fortunately these are now available on the market.

Getting tested for MTHFR

Firstly, I believe all people should have their MTHFR gene analysed after age 30. Below the age of 50, if people are struggling with infertility or mental health issues, taking this fourth-generation folic acid may certainly improve the situation.

When you reach 50, I would suggest you have the MTHFR gene performed if this has not already been done. This should be done along with a blood homocysteine level. Homocysteine is a toxic amino acid generated by this gene abnormality. Elevations above 10 micromoles/L are associated with an increased risk for a number of conditions. I would also suggest a check of the B12 and folic acid level.

The aim is to have homocysteine levels less than 10 but ideally less than 7. We also should be consuming natural sources of folate with 2 to 3 pieces of fruit per day and 3 to 5 servings of vegetables per day. In particular, leafy green vegetables which contain a significant amount of folate are also important. This is particularly important in people who are at high vascular risk; cognitive impairment; bowel cancer risk; infertility and low B12.

People in these groups need to be particularly concerned about what type of folic acid they take in supplement form.

I believe there has not been enough emphasis on the 50% of people in society who have the MTHFR gene abnormality. It is fortunate that we now have a simple and highly effective solution to this issue.