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Vitamin D, vitamin A, and lung cancer in the USA

Posted on: August 31, 2012   by  John Cannell, MD

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I have repeatedly warned about vitamin A. I am not the first. As early as 1933, Professor Alfred Hess, who discovered that sunlight both prevented and cured rickets, warned about vitamin A consumption, writing in JAMA,

“…as to a requirement of thousands of micrograms of vitamin A daily, the unquestionable answer is that this constitutes therapeutic absurdity, which, happily, will prove to be only a passing fad.”

He was wrong about it being a passing fad. Four years ago, I got 16 nutrition experts together, including Professor Walter Willett at Harvard, to warn about vitamin A once again:

Cannell JJ, Vieth R, Willett W, Zasloff M, Hathcock JN, White JH, Tanumihardjo SA, Larson-Meyer DE, Bischoff-Ferrari HA, Lamberg-Allardt CJ, Lappe JM, Norman AW, Zittermann A, Whiting SJ, Grant WB, Hollis BW, Giovannucci E. Cod liver oil, vitamin A toxicity, frequent respiratory infections, and the vitamin D deficiency epidemic. Ann Otol Rhinol Laryngol. 2008 Nov;117(11):864-70. Review.

We said,

“Although activated vitamin D and vitamin A signal through common cofactors, they compete for each other’s function. Retinoic acid antagonizes the action of vitamin D and its active metabolite. In humans, even the vitamin A in a single serving of liver impairs vitamin D’s rapid intestinal calcium response. In a dietary intake study, Oh et al found that a high retinol intake completely thwarted vitamin D’s otherwise protective effect on distal colorectal adenoma, and they found a clear relationship between vitamin D and vitamin A intakes, as the women in the highest quintile of vitamin D intake ingested around 10,000 IU/d of retinol.”

We also stated,

“Furthermore, the consumption of preformed retinol — even in amounts consumed by many Americans in both multivitamins and cod liver oil — may cause bone toxicity in individuals with inadequate vitamin D status. Women in the highest quintile of total vitamin A intake have a 1.5-times elevated risk of hip fracture. Indeed, a recent Cochrane Review found that vitamin A supplements increased the total mortality rate by 16%, perhaps through antagonism of vitamin D. Another recent Cochrane Review concluded that although vitamin A significantly reduced the incidence of acute lower respiratory tract infections in children with low intake of retinol, as occurs in the Third World, it appears to increase the risk and/or worsen the clinical course in children in developed countries.”

Now a brand new study confirms the detrimental effects of vitamin A in the USA and certainly in cod liver oil countries in Scandinavia. Dr Ting-Yuan Cheng and Marian Neuhouser of the University of Washington looked at the interaction of vitamin D with vitamin A in lung cancer in the USA.

Cheng TY, Neuhouser ML. Serum 25-hydroxyvitamin D, vitamin A, and lung cancer mortality in the US population: a potential nutrient-nutrient interaction. Cancer Causes Control. 2012 Sep;23(9):1557-65. Epub 2012 Jul 25.

Expectedly, they found that “vitamin D sufficiency was associated with a 50-70% decrease in lung cancer mortality among nonsmokers.” Unexpectedly, to most, they found, “These beneficial associations were not observed among those with high concentrations of circulating vitamin A or users of vitamin A dietary supplements.” However, the statistical evidence of effect modification was limited by the few lung cancer deaths in their cohort.

They also found that the majority of Americans had elevated levels of retinyl esters and that 29% of Americans have potentially toxic levels. Vitamin A is found in so many foods that the thousands of ugs per day of vitamin A that Professor Alfred Hess warned about many years ago is easily obtained from diet alone. However, Americans may ingest as many as 5,000 ug/day due to diet, cod liver oil, and multivitamins containing retinyl acetate or retinyl palmitate. Some people even take pure vitamin A supplements.

In the undeveloped world, vitamin A food fortification, varied diets, and colorful vegetables are rare among people subsisting on a single carbohydrate source (rice, wheat, etc.), and vitamin A deficiency is common. However, in developed countries, as Drs. Cheng and Neuhouser showed, the problem is sub-clinical vitamin A toxicity, probably working by countering the effects of vitamin D.

As I have hypothesized repeatedly, I believe the vitamin A toxicity in developed countries explains the U-shaped curves we sometimes see in vitamin D studies, especially in the cod liver oil countries. See some of my other writings that cover this topic:

10 Responses to Vitamin D, vitamin A, and lung cancer in the USA

  1. Rebecca Oshiro

    I gave a guest lecture on vitamin D to the July meeting of the Weston A. Price Foundation’s Seattle chapter last month. The cod liver oil debate is a touchy subject with them and one I was anxious to avoid, which inevitably came up. I now believe that the “miraculous” improvements Dr. Price saw with administration of cod liver oil to sickly American children and adults were due to the correction of severe nutritional deficiencies that were rampant in the first half of the last century. In Dr. Price’s time the population at large did not have access to an adequate diet, and as a result many suffered subclinical and outright nutritional deficiencies. The government knew this, and some of the earliest predecessors to the food pyramid (now MyPlate) had a special category for orange and yellow vegetables to encourage a higher intake of beta carotene. Greater access to these vegetables, along with more leafy greens, would have improved nutritional status to such a point there would have been nothing for the cod liver oil to correct.

  2. Brant Cebulla

    A 2×2 rct using vitamin D and vitamin A, similar to the VITAL study (using vitamin D and omega-3s), would be really interesting. I know in mice models they’ve looked at bone health after administering vitamins A and D. Perhaps looking at bone health in humans in a small 2×2 rct would be the place to start and further this debate.

  3. Carol

    I have just started the Gut and Pshycology Syndrome protocol for my food inoterances, chronic fatigue and fibromyalgia. In her book, Dr. Natasha Campbell-McBride is adamant about usng fermented cod liver oil for the benefit of the cholesterol in it, as well as the vitamins A and D. So I have decided to continue taking the 5000 IU of Vitamin D (or maybe less) that I have been on for quite some time, as well as a capsule or two of the fermented cod liver oil. This doctor is against using other types of Cod Liver Oil in which the vitamins have been added back. I am wondering if you would agree with that differentiation. Also she maintains that people with “GAPS” generally do not readily absorb the needed vitaimins so might need extra.

  4. John Cannell, MD

    the majority of Americans have elevated retinal esters, the only blood test that can determine vitamin A levels.

    Ask your doctor for a retinal esters test if you think you are vitamin A deficiency (you are not).

    John

  5. Dan

    Does the body regulate conversion of Beta-Carotene into Retinol so no danger from multi-vitamin with high beta-carotene?

    • Brant Cebulla

      @Dan, I wouldn’t say there is no absolute danger, but the body does convert beta-carotene to retinol on an as-needed basis and discards the rest, so it’s thought to be safer than acetate or palmitate, especially if you’re going to supplement with some form of vitamin A.

      I caution in saying “no absolute danger” because there was a famous trial in the 80s that used beta carotene that was 30 times the amount you would get from diet to see if it prevented cancers. It didn’t, in fact increased risk. That being said, if you stay away from taking 30 times physiologic dose, you’re probably just fine.

      Personally, some of my favorite foods are loaded with beta-carotene way beyond what the RDA is set at. Things like sweet potatoes, carrots, dandelion greens (yeah I’m that guy) and butternut squash.

      Keep in mind that I’m not a nutritionist.

  6. Mark Pegram

    It is a great theory when we find high levels of vitamin A or retinal esters and a disease states exist that the cause is elevated vitamin A. However, since vitamin D and vitamin A work in combination for cellular differentiation, it may be that high levels of vitamin A is just another way of saying you have vitamin D deficiency.

    In the lung cancer study, I do not believe they would have found a worse condition when both levels of vitamins are elevated. My experience has been that an adequate level of all nutrients is necessary for health.

    This leads directly to the error that has long been made in disease studies. That is looking at one suspected cause and ignore the combinations. The reason is that the math gets very complicated in trying to analyze multiple factors. This was solved in the 1970’s in manufacturing by using analyze of the means instead of analyze of the variants. There is smaller data sets required for significance and it gives you the interactions as well. For example, it may be that elevated levels of both vitamin D and Vitamin A would give the best outcome when trying to treat cancer. Analyze of the means also gives clear graphical presentation that is easier to understand by the lay person. For its clarity, it will never be adopted for medical studies.

    I believe the ultimate approach to curing cancer and other diseases will be higher levels of all the things we are deficient in through their synergism of action. Vitamin D, Vitamin C, Vitamin E, Vitamin B, Vitamin A, magnesium, iodine, and sulfate.

  7. Umileritac@aol.com

    Mark,

    How true!

    One would hope that the medical community will one day realize that the most favorable approach to curing cancer (as well as many other diseases) will be at the level of prevention rather than treatment. And, this approach will definitely include providing our bodies with higher levels of nutrients and cofactors aimed at correcting deficiencies, with these various nutrients and cofactors working together for a systematic response to good health.

    The nutrients you mentioned (Vitamin D, Vitamin C, Vitamin E, Vitamin B, Vitamin A, magnesium, iodine, and sulfate) as well as others: zinc and selenium for example are all so very necessary for our optimal wellbeing.

    Let’s also include in this mix appropriate exercise, stress reduction and healthy sleeping habits.

    Good health requires a multi-faceted approach, for sure.

    Although I am not a healthcare professional, it would seem to me that the mechanisms of initiation and progression of cancer most likely include unresolved infection, immune system dysfunction, inflammation, oxidative stress, impaired detoxification and hormonal imbalances. These conditions can affect gene expression, cell growth messaging, angiogenesis and apoptosis.

    Many conventional wisdom doctors turn (too) readily to surgery, radiation or chemotherapy for a slash, burn or poison route. From my layman’s perspective, it appears to me that these methods rarely hold a cure, and disease often becomes recurrent…chronic….

    Perhaps it is time to more seriously explore dietary, nutritional, botanical and other lifestyle therapies as treatment for critical disease. In my opinion it will take the general public to move the conventional medical community on this issue.

    I’m grateful for websites like the Vitamin D Council, which are a source of excellent information; and, which also provide a community of like-minded and supportive individuals.

    To your GOOD HEALTH,

    Rita Umile

  8. John Cannell, MD

    All nutrients are needed but excessive amount of some nutrients, like vitamin A, are detrimental. With all nutrients, one must look at total intake from all sources and not just say the body needs it so I must take a supplement of it.

    The above study found that 30% of Americans are vitamin A toxic and 50% have excess vitamin A in their system. Food fortification with preformed retinol is so extensive in the USA, that is is causing this widespread toxicity.

  9. Dan

    John Cannell, MD said “Food fortification with preformed retinol is so extensive in the USA, that is is causing this widespread toxicity.”

    Yet another reason to eat unprocessed foods in natural states.

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