Beta-carotene and memory

“Taking supplements of beta-carotene – which makes carrots orange – over a number of years may help you remember words and conversations,” reported the Daily Express today.

The newspaper said that a study has found that men who took beta-carotene supplements for more than 15 years had less decline in their memory than men who took placebo. The researchers are reported as saying that people using the supplements in the longer term could reduce their risk of Alzheimer's. However, they also warn that beta-carotene supplements have been found to increase the risk of lung cancer and so smokers should avoid taking these supplements.

This news report is based on a study which found that beta carotene supplementation gave small improvements in overall cognitive function (the ability to think, reason, concentrate or remember) and verbal memory (the ability to verbally recall words) compared with placebo. However, due to this study's flaws, further research is needed before a more conclusive answer as to their actual effectiveness can be made.

Where did the story come from?

Dr Francine Grodstein and colleagues from Harvard Medical School and Harvard School of Public Health carried out this research. The study was funded by the National Institutes of Health, the BASF Corporation (the company that provided the beta-carotene supplements for the trial), Wyeth (a drug manufacturer), and DMS. The study was published in the peer-reviewed medical journal: Archives of Internal Medicine.

What kind of scientific study was this?

This was a randomised controlled trial called the Physicians’ Health Study II (PHSII). This study followed on from an earlier study, the Physicians’ Health Study (PHS), which was a randomised controlled trial conducted between 1982 to 1995, comparing the effects of beta-carotene, aspirin, and placebo on cancer and heart disease in male doctors.

The Physicians’ Health Study II (PHSII) ran from 1997 to 2003. The researchers enrolled 7,641 of the men who had participated in PHS, and asked them to continue taking beta carotene supplements (50 mg every other day) or placebo as they had done in the earlier study. The researchers also enrolled and randomly assigned to either of these treatments an additional 7,000 male doctors aged 55 years and over, who had not had cancer or liver disease, and whose kidneys were functioning well.

The participants were blinded to which treatment they were receiving. Every year, researchers sent participants a questionnaire to ask them if they had been taking their treatments, and to ask about their health.

The researchers had not originally planned to look at cognitive function when they set up PHSII , and added this aspect to the study in 1998. For this part of the study, 5,956 of the participants over the age of 65 years completed tests of their cognitive function by telephone. These 5 tests assessed verbal memory and cognitive status.

The researchers then compared the cognitive performance of the men taking beta-carotene with those taking a placebo. Because the men who had been taking beta-carotene in the original PHS would have been taking the supplement for much longer (on average 18 years) than those men recruited specially for the PHSII (who took the supplement for one year on average), analyses were also carried out separately for these groups.

What were the results of the study?

When the researchers analysed all the participants together, they found that beta-carotene supplementation gave small improvements in overall cognitive function and verbal memory compared with a placebo.

When they looked only at the men newly recruited for the PHSII, who had been taking supplements for one year on average, they found no difference in cognitive performance between those taking beta carotene and those taking a placebo.

In the men who had been enrolled in the PHS, who had been taking supplements for 18 years on average, beta-carotene improved overall cognitive function  and verbal memory compared with a placebo.

Researchers estimated that long-term beta-carotene treatment delayed cognitive ageing by about one to one and a half years.

What interpretations did the researchers draw from these results?

Researchers concluded that long-term (15 years or more) beta-carotene supplementation gave modest improvements in cognitive performance, but that short-term (less than three years) beta-carotene supplementation did not.

They suggest that even these modest improvements may indicate that beta-carotene may lead to a “substantial” reduction in the risk of developing dementia.

What does the NHS Knowledge Service make of this study?

This study does indicate some possible benefits of long-term beta-carotene supplementation, but there are limitations, some of which the authors acknowledge:

• Men who had been enrolled in the PHS who agreed to enrol in the PHSII continued to take their originally assigned treatment, rather than being randomly assigned to either beta-carotene or a placebo again. Presumably, this was done because reallocating them would have introduced the problem that the men who had taken beta-carotene for a long period (18 years on average) may have already benefited from beta-carotene. However, this strategy could lead to imbalances between the beta-carotene and placebo groups, which could also affect results. Although the researchers compared the groups and found that they were similar for the characteristics assessed, they may have been imbalanced for other factors that could have affected results. For example, if all people with poor cognition dropped out of the PHS, the people who carried on might have an unrepresentative level of cognitive function.
• As researchers only decided to look at cognitive performance towards the end of their study, they did not assess cognitive performance at the start of the study – so they could not know whether the groups had similar abilities to start with.
• Men in this study were all doctors, and this may have made them more likely to take their supplements regularly than the general population. Because this population was highly selected (i.e. all male, well educated, and generally quite healthy) these results may not apply to other groups of people, such as women, people with less education, or people who are less healthy.
• People in this study were also randomised to receive vitamin E, ascorbic acid, or multivitamins. Receiving these additional supplements could have affected results, but the authors of this paper did not explore this.
• As the participants in this study took beta-carotene in the form of supplements we cannot assume that the same results would be seen if the participants had eaten “a carrot a day”, as suggested by one newspaper headline.

The improvements seen in this paper were small, and researchers note that other, shorter term, randomised controlled trials have found no benefits in cognitive performance with beta-carotene, while some observational studies have found benefits, particularly with long-term use.

These mixed results suggest that we cannot yet be sure of the cognitive effects of beta-carotene, and that we need more research to confirm whether beta-carotene has any role to play in the prevention of cognitive decline and dementia.

The causes of Alzheimer’s disease in particular (a form of dementia with certain characteristic features where no medical, psychiatric or other cause can be identified) are still largely unknown. The newspaper coverage may lead the public to believe that they will reduce their risk of Alzheimer’s by taking beta-carotene, but this still remains to be seen.

Sir Muir Gray adds...

I like carrots, but won't eat any more as a result of this study or go and buy beta-carotene pills. To keep my memory fit I am trying to use it more and at present I am learning Italian.