• Why The Latest Study On Vitamin Supplements May Not Be Instructive To You

    Posted June 24, 2013: by Bill Sardi

    Dr. Paul A. Offit is running around promoting his anti-vitamin pill book saying seemingly harmless antioxidant pills may actually produce elevated mortality rates.  Dr. Offit drags up old flawed and refuted studies, some explained away by the fact mega-dose antioxidants may compete with other nutrients (example: beta carotene as a precursor for vitamin A competes for storage in the liver with vitamin D), or that sicker individuals tend to take antioxidant supplements in higher doses.

    A mathematical trick often used to unduly alarm the public over the dangers of dietary supplements is to exaggerate the numbers.  If 1-in-1000 non-users of antioxidant pills experiences cancer and 2-in-1000 users develop cancer, then the increased risk is said to be 50%!  A naïve public believes that to be 50 in 100 more individuals will come down with cancer if they take antioxidant pills.

    But that is a relative increase in risk.  In hard numbers the absolute risk increased from 1/10th of one-percent to 2/10ths of one-percent.  This is an insignificant and impractical difference that often extends beyond the statistical range of accuracy to predict risk.  Yet this mathematical trick is used every day to approve drugs and demean dietary supplements.

    In the now infamous beta carotene smokers trial in Finland which Dr. Offit repeatedly cites, a study that was published in The New England Journal of Medicine in 1994 just prior to the a vote in Congress that would keep dietary supplements from being classified as drugs, the difference in the incidence of lung cancer between smokers who received beta carotene (474 of 14,560 subjects or 3.225%) and those who didn’t receive beta carotene (402 of 14,573 subjects or 2.758%) was just one-half of one percent, or 1 in 200 subjects.

    The difference in lung cancer deaths among smokers given beta carotene (302 of 14,560 subjects or 2.074%) versus those who did not take beta carotene pills (262 of 14,573 subjects or 1.798%) was a trivial one-quarter of one-percent or about 1 in 400 individuals.

    It is difficult to imagine the precision (plus or minus variance) with which this study predicted lung cancer or lung cancer death was sensitive enough to reliably predict such small differences accurately.  In practical terms, the warning was meaningless.  Smokers should stop smoking, not stop taking antioxidant pills!

    Surveys of estimated intake or actual blood levels?

    Also, often the difference in mortality rates between mega-dose and lower-dose antioxidants is trivial and are based on surveys, not actual blood levels of these antioxidants.

    A recent example is a study conducted in France.  DHA-rich fish oil did not significantly reduce the risk for the fast-progressive form of macular degeneration.  But in a sub-group that did experience measurable increases of DHA-fish oil in their blood serum, there was a dramatic decrease in the risk for this form of the disease.  Unless blood levels or tissue levels of nutrients are obtained, it cannot be completely ruled out that supplemental antioxidants are not beneficial.

    In better designed studies, both information from health and lifestyle questionnaires and blood plasma levels of nutrients are obtained.  For example one such study did attempt to correlated vitamin blood levels and all-cause mortality, which certainly is the most meaningful measure of benefit.  What this study found was higher vitamin C and D blood concentrations were associated with lower all-cause mortality rate.  Obviously this is not a study Dr. Offit cites.

    Reaching the intended target tissue

    Supplemental antioxidant vitamins may be ineffective simply because they are not reaching their intended target tissue.  For example, supplemental vitamin D may not achieve higher blood levels of this vitamin because in obese patients this fat-soluble vitamin may be stored in fatty tissue rather than transported properly.  Another antioxidant nutrient, lutein, which is important for the health of the human retina, may not adequately reach the retina in obese individuals.   This doesn’t mean these food supplements are ineffective per se, it means body metabolism may need to be altered to achieve a measurable benefit.

    Is the antioxidant found in the tissue being studied?

    Another important factor to asses in analyzing nutrient studies is whether the nutrient under study is even present in the organ or tissue being examined.

    For example, studies show the lycopene, the antioxidant red pigment found in tomatoes and watermelon, is associated with a significant reduction in the risk for macular degeneration.   However, lycopene is not found in the macula (visual center of the eye).  So it must have an indirect effect or be associated with some other beneficial factor.  Maybe individuals who consume a lot of lycopene also consume a lot of lutein, and lutein, which IS found in the macula, protects the macula.

    Fat-soluble versus water-soluble antioxidants

    Generally speaking, fat-soluble nutrients such as vitamins A, D, E and K and carotenoids (lutein, lycopene and beta carotene) target fatty tissues while water-soluble nutrients (such vitamin C and all the B vitamins) are deposited in non-fatty tissues, mostly in the extracellular tissue (gooey stuff) outside of living cells.

    The brain is very fatty and fat-soluble nutrients like vitamin D and E are more likely to be beneficial in the brain while water soluble vitamin C, which is largely an extracellular (outside the cell) antioxidant, is not likely to be of benefit.  To say that vitamin C supplements fail to exhibit any benefits for the brain may be a predetermined conclusion.

    For example, in one study vitamin E and nuts (which are fatty) were associated with a reduced risk for Parkinson’s disease (a movement disorder caused by disequilibrium of chemicals in the brain), but not water-soluble vitamin C.

    Vitamin depleting drugs may negate a study

    In many instances, especially in large human clinical trials such as for heart disease, there may be a sufficient number of patients taking vitamin-depleting drugs to mask whether an antioxidant vitamin may provide a health benefit.  For example, in a study that involved 11,178 senior adults who were taking antioxidant vitamins, 418 of these elderly subjects took vitamin C alone (no other antioxidants), but 26.8% of these 418 subjects were taking aspirin tablets, 6.7% were active smokers and 34.9% were alcohol drinkers, all health habits that deplete vitamin C.  Blood concentrations of vitamin C were not obtained.  It is not surprising the study concluded vitamin C did not significantly lower the risk for mortality.

    Data pertains to groups, not individuals

    The primary reason why large human trials may not be instructive to individuals is because they only provide information that pertains to large groups, not individuals.

    For example, in a study of 2889 elderly adults 65-102 years of age, 449 who took vitamin E supplements, the data from this study was assembled into 5 groups from the lowest to the highest intake levels of vitamin E intake.  The risk of mental decline was significantly lower (-36% relative risk) among a group that consumed the most vitamin E versus a group whose intake of vitamin E was the lowest.  But the problem with this type of study is that there is no way of knowing which group an individual is in by reading the study alone.  Vitamin E intake may need to be assessed and blood levels obtained to adequately estimate risk reduction.

    Furthermore, another illogical assumption is often made.  An individual may be in the lowest intake group and would theoretically benefit from taking a vitamin E supplement, or they may be in the highest intake group and already experience a benefit in comparison to the group that is insufficient.  But if the five groups were all sufficient in vitamin E, then the study might misleadingly conclude vitamin E is of no benefit within the dosage range studied.

    Therefore, the large human clinical trials Dr. Offit cites to condemn antioxidant supplements are simply not instructive to individuals who read his book.

    What is needed is health care based on an individual’s particular situation (personalized medicine) rather care protocols based upon lumped data among groups of people.  Most of modern medicine is based upon a flawed methodology.

    Duration of use

    Another aspect to assess in evaluating antioxidant supplements is whether there was adequate duration of use to produce a measured effect.  For example, cataracts (cloudiness in the focusing lens of the eyes) emanate from slowly progressive loss of transparency (1% decline) per year.  Use of an antioxidant supplement for a short period of time may not produce a measurable effect.  Sure enough, only women who took a vitamin C supplement for 10 years or more had a significant reduction in their risk for cataracts.

    Studying the wrong disease

    Another pitfall in evaluating antioxidant supplements is studying the wrong disease.  For example, a study showed that supplemental vitamin C does not reduce the risk for ischemic (iss-keem-ik) stroke (lack of blood supply to the brain).  Yet supplemental vitamin C may prevent hemorrhagic (bleeding) strokes.  Smokers incur a greater risk for this type of stroke and smoking depletes vitamin C. Smoking depletes the pool of vitamin C stored in the body.  Low vitamin C levels can result in weak capillaries and hemorrhage.   So it would be incorrect to say vitamin C does not prevent strokes.  About 20% of strokes are hemorrhagic.

    Researcher bias

    A lay reader is going to have a difficult time detecting bias in antioxidant supplement studies.

    Dr. Paul Offit, speaking out in The New York Times, says “a review published in 2005 in the Annals of Internal Medicine found that in 19 trials of nearly 136,000 people, supplemental vitamin E increases mortality.

    But a reading of that study found this statement:  “Precise estimation of the threshold at which risk increases is difficult” given that “high-dosage (> or =400 IU/day) trials were often small and were performed in patients with chronic diseases. The generalizability of the findings to healthy adults is uncertain.”

    In fact, a more recent meta-analyses involving 57 studies from 1988 to 2009 showed that supplementation with vitamin E appears to have no effect on all-cause mortality at doses up to 5,500 IU/day.  Dr. Offit appears to be cherry-picking negative studies involving antioxidant supplements.

    In another example of author bias, a study in published in the British Journal The Lancet in 2001 concluded there was no significant reduction in the mortality rate for vitamin C users but did report that for every 20 micromole per liter increase in vitamin C concentration from foods, which would require an increase of about one serving of fruits of vegetables, there was a significant (~30%) reduction in mortality.  Only fruit and vegetable intake correlated consistently with more vitamin C versus other foods.  (The proportion smokers in this study was proportionately low compared with national data.  Smoking depletes vitamin C).

    However, dietary intake levels of vitamin C among males were 51, 77, 83, 92 and 109 milligrams from the lowest to highest of five divided groups studied.  That would not be enough vitamin C to measurably increase vitamin C blood serum levels alone because vitamin C by itself is washed out of the body within 30 minutes of consumption.  Yet the vitamin C blood levels across these five groups progressively rose from 20.9, 38.3, 49.1, 57.6 to 73.3, about a 350% difference from lowest to highest blood concentration.

    Obviously something in fruits and vegetables causes vitamin C to be more slowly absorbed or less quickly excreted.  Bioflavonoids in fruits (citrus rind) has been shown to slow absorption and excretion of vitamin C and may be a reason by vitamin C supplements alone don’t always produce health benefits.  It could be that vitamin C supplements that include bioflavonoids are more beneficial for this reason.  Were these researchers remiss in not recommending bioflavonoids be included with vitamin C supplements?

    Investigators Steve Hickey and Hilary Roberts advise frequent repeated doses of vitamin C to achieve optimal health benefits.  Studies that involve a single dose of vitamin C in a day simply ignore the known dynamic flow of vitamin C in the body.

    Bottom line, don’t be quick to write off antioxidant supplements.  ©2013 Bill Sardi, Knowledge of Health, Inc.

    Share

Leave a Reply

You must be logged in to post a comment.