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Do vitamins A and D work together to help reduce the risk of lung cancer?

Posted on: November 9, 2014   by  Jeff Nicklas


New research published in International Journal of Cancer found that vitamin D reduces the risk of lung cancer among a high-risk group of smokers and workers exposed to asbestos, and that vitamin A might play a role in vitamin D’s effects on this risk.

We frequently get questions asking about the ways in which other vitamins and minerals interact with vitamin D. These often involve whether it is necessary to take other vitamins in addition to vitamin D, or if certain nutrients interfere with or enhance vitamin D’s beneficial effects on health.

While it is not required to take other vitamins and minerals with vitamin D, there is evidence to suggest that certain nutrients work synergistically with vitamin D to perform very specific functions.

Vitamin K and magnesium, two nutrients that are commonly inquired about, have been suggested to work with vitamin D to transfer calcium to the bones from soft tissue and activate vitamin D, respectively.

Vitamin A has also been suggested to work in tandem with vitamin D to help ensure that genes function properly and has been suggested to be involved with vitamin D metabolism. However, it is also suggested that taking too much vitamin A can interfere with vitamin D’s functioning in the body.

These physiological interactions are often reported on, but what about the relationship between vitamin D and other nutrients in regards to specific conditions and diseases?

Until recently, not much research has been conducted on this topic regarding vitamins A and D. Researchers based out of Seattle recently conducted a study to look at vitamin D’s relationship with lung cancer risk and whether or not vitamin A influenced this relationship.

To conduct their analysis, the researchers looked at data from the Carotene and Retinol Efficacy Trial (CARET). CARET was a randomized controlled trial of 18,000 individuals aged 50-69 years old that was initiated in 1985 to determine the effects and safety of daily 30mg beta-carotene plus 25,000 IU retinyl supplementation on cancer prevention.

For the current study, the researchers looked at data from 749 participants from the study that developed lung cancer over the course of the original trial and 679 participants who didn’t develop lung cancer to serve as a control group.

At the start of CARET, all participants were given a food frequency questionnaire. The researchers used data from these questionnaires to quantify and estimate the total intake of vitamin D from dietary sources.

During CARET, the participants reported their personal supplement use by bringing their bottles in to be recorded at the clinical visits. The researchers used this data, along with the questionnaires, to calculate the estimated intakes of vitamin D and vitamin A.

Data from other questionnaires were collected to determine things like age, gender, education level, smoking habits, and number of years in an occupation with asbestos exposure.

A participant was considered a current smoker if they had smoked a cigarette in the past month, and were considered a former smoker if they had quit smoking in the past 6 years.

The researchers were interested in a number of variables when looking at all of this data. They first wanted to determine if vitamin D intake measured at baseline was related to risk of developing lung cancer.

They then wanted to see if personal vitamin A supplement use or if the high-dose vitamin A administered in the original trial modified the relationship seen between vitamin D and lung cancer risk.

Here is what they found for vitamin D’s relationship with risk of lung cancer:

  • There was no significant relationship between vitamin D intake and risk of lung cancer in all participants.
  • There was an inverse relationship between vitamin D intake and lung cancer among former smokers, however this only approached significance (P-trend = 0.06).
  • Compared to an intake of less than 200 IU/day, a vitamin D intake of 600 IU/day or greater was related to a 64% reduced risk of non-small cell lung cancer among former smokers (P-trend = 0.08).
  • There was a non-significant 11% reduced risk in lung cancer for every increase of 100 IU of vitamin D.

The researchers then looked at whether or not vitamin A influenced these results. Here’s what they found in this secondary analysis:

  • Among all participants receiving the high-dose vitamin A from the trial, vitamin D intake of 400 IU/day or greater had a 44% reduced risk of lung cancer compared to those with an intake of less than 400 IU/day.
  • Among all participants, those with a vitamin D intake of 400 IU/day or greater had a significantly reduced risk of 54% for lung cancer only if they had a vitamin A intake of 1,500 mcg/day or greater.
  • These results were also seen in former smokers, but not current smokers.

The researchers commented,

“In conclusion, high total vitamin D intake is associated with a lower risk for non-small cell lung cancer among CARET former smokers. Vitamin A intake from diet and supplements may assist vitamin D in preventing lung cancer among smokers.”

This study is not without its limitations. Vitamin D intake was estimated only at baseline and no blood levels were measured. This means we do not know exactly how much vitamin D the participants were getting and what levels might be needed to see these effects.

Furthermore, the study group was highly specific and consisted only of heavy smokers and those chronically exposed to asbestos, which means that we cannot generalize these results to other populations.

While these results cannot prove causation and don’t apply to the general population, they do hint that a unique interaction might exist between vitamin D and vitamin A that influences lung health.

The current evidence is not sufficient to recommend that high doses of supplementary vitamin A are needed when supplementing with vitamin D in order to reduce the risk of developing lung cancer. Future research looking at different populations is needed to confirm this interaction with regards to lung cancer.


Cheng, T. et al. Estimated intake of vitamin D and its interaction with vitamin A on lung cancer risk among smokers. International Journal of Cancer, 2014.

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