Aluminum in chlorella and other foods

Aluminum is one of the most abundant elements on earth and is correspondingly present in both food and water supplies. It is not a toxic heavy metal and so it is not routinely tested in foods or other raw materials, but the reported levels in chlorella are still low compared to common produce and other food staples; and chlorella’s serving size is also much smaller, which minimizes any potential risk even more.  

 

Aluminum in foods is not a cause for concern for toxicology experts because orally consumed aluminum is not considered to be very bioavailable from the gut, nor persistent in the body. Less than 1% is typically absorbed from our G.I. tracts, and virtually all of that has been shown to be excreted in the urine or feces. (Injectable sources, such as vaccine adjuvants, present a separate issue as absorption is not constrained by an effective gut barrier.)

 

Some companies tout lower levels of aluminum in their chlorella products as a marketing distinction, but admit that the levels being compared are far lower than in most common foods that are considered very healthy, i.e. cruciferous vegetables; despite the overwhelming safety data showing no real risk from consuming these foods that are normally considered to be good for us.

 

Here is a toxicology evaluation of dietary aluminum safety: https://www.ncbi.nlm.nih.gov/pubmed/11259180

Is Carrageenan Safe or Dangerous?

Undenatured carrageenan is a natural stabilizer, binding agent, and emulsifier used in products such as toothpaste in place of SLS and other truly undesirable ingredients commonly used in mass market products. It is also used in some vegan-friendly softgel capsule material as an alternative to animal-derived gelatin.

There is an Internet myth that carrageenan is unsafe; due primarily to confusion with a so-called “denatured carrageenan” polymer that is actually poligeenan, a heavily processed low molecular weight seaweed derivative currently used only as an x-ray imaging component. Poligeenan, previously used in pharmaceuticals, is quite different from the undenatured high molecular weight material that we use. Due to the safety concerns over poligeenan, regulations routinely require the carrageenan added to foods to have high molecular weight to ensure its integrity. But there are no unresolved safety concerns with undenatured carrageenan. 

Carrageenan has been thoroughly vetted by national and international public health authorities over a number of decades, even recently in response to the ongoing blogger-driven controversies, so there is no remaining basis of concern. Even its use in infant formulas was recently reconfirmed to be safe, and it’s helpful in distributing the nutrients more evenly to avoid the settling out that could otherwise cause uneven nutrient intake when a bottle is only partially consumed. 

After repeated investigations, the evidence for carrageenan safety is stronger than ever. Carrageenan is extremely safe and present in a number of healthy seaweeds; only the denatured form of carrageenan - a drug - is toxic. 

References:        

·        Public health and carrageenan regulation: a review and analysis. Borowitzka et al. (eds.), Nineteenth International Seaweed Symposium. DOI: 10.1007/978-1-4020-9619-8_8. Developments in Applied Phycology.

·         http://www.ncbi.nlm.nih.gov/pubmed/24467586

·         http://www.foodproductdesign.com/blogs/formulating-foods/2014/07/fao-who-carrageenan-safe-in-infant-formula.aspx

·         http://www.ncbi.nlm.nih.gov/pubmed/12389870

·         http://www.foodinsight.org/blogs/why-you-should-care-about-carrageenan

U.S. Increases Recommendations for Vitamin D Intake but Misses the Mark

U.S. Increases Recommendations for Vitamin D Intake but Misses the Mark

As you probably know from news reports, the recommendations for individual consumption of vitamin D has now increased, as has the tolerable Upper Limit (UL) that indicates a higher intake level at which the vast majority of people will not suffer any unpleasant side effects. But these recommendations are controversial for being too conservative, and at the same time the report has been sensationalized in the popular media with an inappropriate emphasis on possible side effects of megadoses.

The Institute of Medicine (IOM), the health arm of the National Academy of Sciences, is an independent, nonprofit organization that works outside of government to provide unbiased and authoritative advice to decision makers and the public. Through more than three dozen sets of guidelines, known as Dietary Reference Intakes (DRIs), IOM provides estimates of the amounts of nutrients that individuals need to consume each day. Health care professionals and policy makers, including federal nutrition officials who develop nutrition programs as well as the food industry, rely on this guidance from the IOM. The reference numbers that you see on food and dietary supplement labels, such as Daily Values (DV), DRIs, and Recommended Daily Allowances (RDAs), are generated by IOM. (1) These values are also utilized by some foreign governments as authoritative references on which to base their own food and supplement regulations.

The good news is that, in a report issued by IOM on November 30, 2010, the RDA has now increased by 50% (from 400 IU to 600 IU) and the tolerable Upper Limit has now doubled (from 2,000 IU to 4,000 IU). Also, the RDA for adults over 71 years old has increased to 800 IU daily. (2) This means that the new recommendations are often higher than the 400 IU that is found in a typical multivitamin or calcium+D formula, thus requiring additional supplementation to meet the RDA. And the leeway for safe use at the upper end is now double what it was before, making such supplementation at higher levels still within a margin generally accepted as safe; at least up to 4,000 IU, though as usual that number is deliberately set low and has a large safety margin.

IOM’s report stating that most Americans have adequate circulating levels of vitamin D is somewhat controversial, as it utilizes a standard of 20 ng/mL (equivalent to a measure of 50 nmol/L) (3) that is not universally accepted as adequate for optimal health by many modern vitamin D researchers. While that amount may adequately support bone health, which was (as usual) the primary focus of the IOM committee, there are vitamin D receptors on many other human cells and this vitamin reportedly plays an important role in cardiovascular disease (4), immune health (5), prostate and breast health (7), blood sugar metabolism (6), cancer prevention (7,8) , and a host of natural processes. One recent report stated that, “The desirable serum 25 (OH) D levels is at least 100 nmol/L, a level that has generally been found to provide most of the health benefits of vitamin D.” (9) This recommendation is twice as high as the new RDA, evidencing the controversial nature of IOM’s RDA process.

However, the IOM committee admittedly based its recommendations solely on vitamin D’s effects on bone health after reviewing numerous studies on other benefits and concluding that more study is required to generate the level of evidence that IOM requires to set its recommendations. Committee chair Catharine Ross was quoted as saying, “Amounts higher than those specified in this report are not necessary to maintain bone health.” (10) As the amount of science in these other areas grows, so should the levels recommended for general health. But statements such as that by Dr. Ross that “people don't need more than the amounts established in this report” refer only to bone health and should not be construed as denying the fact that other benefits at higher levels of intake have been reported, though not as consistently as the IOM committee would need to accept them as conclusive enough to revise its recommended levels upward.

Based on current research, natural health advocates typically recommend levels 50-100% higher than the IOM report recommends in order for people to obtain the full protective benefits of vitamin D, and many physicians who test for this vitamin ask their patients to meet or exceed that higher level. This is perhaps the most controversial part of the report, and I predict that a barrage of higher numbers appearing in medical reports as protective will force another overdue round of RDA changes in perhaps another 10-15 years. In my opinion, the IOM is always behind the times in the area of nutrient recommendations, being by nature super cautious. We dared to hope, but nobody really expected the IOM panel to accept the evidence of recent published review studies in medical journals and raise both the RDA and UL to the recommended five times their previous levels, and frankly we were not surprised that they didn't. These special panels are typically very conservative and hesitant to make dramatic changes, and are comprised with well-qualified general nutrition experts but not with experts in the particular area in question who might push for acceptance of higher levels.

People have already been taking over 2,000 IU daily, the old tolerable Upper Limit, without apparent harm and will probably continue to take over the new 4,000 IU UL as well. Clinical science indicates that higher levels are still quite safe, at least up to 10,000 IU daily for most adults. In 2007 a review published in the American Journal of Clinical Nutrition applied the same risk assessment methodology used by the Food and Nutrition Board (FNB) to derive a proposed revision of the safe Tolerable Upper Intake Level (UL) for vitamin D. (11) Noting an absence of toxicity in trials conducted in healthy adults that used a vitamin D dose ≥250 µg/d (up to 10,000 IU of vitamin D3), a new UL of 10,000 IU was confidently proposed, but was apparently not accepted by the IOM. Nor was the recommendation for a new RDA to be raised to 2,000 IU.

In fact, the 10,000 IU daily UL proposal may have been conservatively low; so what does that make the revised tolerable UL of only 4,000 IU? According to a report in the journal Nutrition Reviews, "The input needed for efficacy, in addition to typical food and cutaneous [sunlight] inputs, will usually be 1000-2000 IU/day of supplemental cholecalciferol [vitamin D3]. Toxicity is associated only with excessive supplemental intake (usually well above 20,000 IU/day)." (12) [Italicized words added for clarity]

Dietary supplement manufacturers already were not allowed to make disease claims on dietary supplements without (always reluctant) FDA approval, so the IOM’s report that vitamin D has not been proven to prevent various diseases is not news for them. However, consumers will continue to be exposed to positive reports on the vitamin and most will understand that just because it has not yet been "proven" to prevent certain diseases doesn't mean that it doesn't, especially at levels higher than needed purely for bone health, nor does it suggest that there is no supporting evidence that it still may be an important preventative factor.

The government standard of proof in the dietary supplement area has been frequently criticized and the FDA in fact has lost several federal court cases, where courts have ordered the agency to comply with the law allowing such claims where substantial evidence already exists for some supplements’ role in disease prevention (for example, selenium and cancer). (13,14) Of course, almost never is anything "proven" in a scientific field; theories rule most scientific endeavors. But that should not suffice to allow the government to muzzle legitimate science nor to prevent the public from taking natural nutrients at levels that they may require due to their own individual biochemistry and relevant environmental factors. In this case, the new RDA and UL are simply baby steps in the right direction, but perhaps the full knowledge of vitamin D’s health benefits is still in its infancy.

REFERENCES:

1. http://www.iom.edu/About-IOM.aspx Accessed November 30, 2010
2. Dietary Reference Intakes for Calcium and Vitamin D. Food and Nutrition Board, Institute of Medicine, National Academies. Released: November 30, 2010
3. http://ods.od.nih.gov/factsheets/VitaminD-Consumer/ Accessed November 30, 2010
4. Wallis DE, Penckofer S, Sizemore GW. The "sunshine deficit" and cardiovascular disease. Circulation. 2008 Sep 30;118(14):1476-85. Review. Erratum in: Circulation. 2009 Jun 2;119(21):e550. PubMed PMID: 18824654.
5. Cannell JJ, Zasloff M, Garland CF, Scragg R, Giovannucci E. On the epidemiology of influenza. Virol J. 2008 Feb 25;5:29. Review. PubMed PMID: 18298852; PubMed Central PMCID: PMC2279112.
6. de Boer IH. Vitamin D and glucose metabolism in chronic kidney disease. Curr Opin Nephrol Hypertens. 2008 Nov;17(6):566-72. Review. PubMed PMID: 18941348; PubMed Central PMCID: PMC2882033.
7. Skinner HG, Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Vitamin D intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiol Biomarkers Prev. 2006 Sep;15(9):1688-95. PubMed PMID: 16985031.
8. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. The role of vitamin D in cancer prevention. Am J Public Health. 2006 Feb;96(2):252-61. Epub 2005 Dec 27. Review. PubMed PMID: 16380576; PubMed Central PMCID: PMC1470481.
9. Grant WB, Schwalfenberg GK, Genuis SJ, Whiting SJ. An estimate of the economic burden and premature deaths due to vitamin D deficiency in Canada. Mol Nutr Food Res. 2010 Aug;54(8):1172-81. PubMed PMID: 20352622.
10. http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=13050 Accessed November 30, 2010
11. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007 Jan;85(1):6-18. Review. PubMed PMID: 17209171.
12. Heaney RP. Vitamin D: criteria for safety and efficacy. Nutr Rev. 2008. Oct;66(10 Suppl 2):S178-81. Review. PubMed PMID: 18844846.
13. http://www.emord.com/FDA_Agrees_to_Allow_Selenium_Qualified_Health_Claims.html Accessed November 30, 2010
14. http://www.kelleydrye.com/publications/client_advisories/0576 Accessed November 30, 2010

Dietary Supplements are now Safely Regulated

TIMELINE:

1994 The Dietary Supplement Health and Education Act (DSHEA)


• Requires manufacturers to follow Good Manufacturing Practices (GMP) set by the FDA


     o GMPs were fully implemented between June 2008 and June 2010


• Continues to define dietary supplements as Food


• Regulates labels

     o All claims must be truthful and not misleading

     o All ingredients must be on the labels

     o Documentation to prove claims must be maintained

• Approves pre-existing dietary ingredients already on the market as of October 15, 1994

     o Common vitamins, minerals, herbs

     o “Grandfathering” was twice applied to pharmaceuticals already on the market:

     o  The 1938 Food, Drug and Cosmetic Act & 1962 Kefauver-Harris Amendments

• Requires pre-market submission to the FDA of all New Dietary Ingredients marketed after October 15, 1994

     o The agency questions the majority of submissions

     o The agency has the power to reject applications; and has done so

     o This is analogous to pharmaceuticals where all drugs entering the market after October 10, 1962 require an FDA submission/approval process


1997 Food and Drug Administration Modernization Act (FDAMA)

• Provides for health claims based on an authoritative statement by a scientific body of the U.S. government or the National Academy of Sciences

• Such claims may be used only after submission of a health claim notification to FDA



2002 The Public Health Security and Bioterrorism Preparedness and Response Act

• All food manufacturers, including dietary supplement manufacturers, are required to be registered with the government and give advance notification of raw materials imports



2003 The FDA Consumer Health Information for Better Nutrition Initiative

• Provides for qualified health claims where the quality and strength of the scientific evidence falls below that required for FDA to issue an authorizing regulation

     o Such health claims must be qualified to assure accuracy and non-misleading presentation to consumers



2004 The Anabolic Steroid Control Act amendment

• Bans steroid precursors sold as dietary supplements

     o The FDA and DEA have authority to take action against adulterated products



2006 The Dietary Supplement and Nonprescription Drug Consumer Protection Act

• Requires reporting of all serious adverse events (AERs) for both dietary supplements and OTC drugs


The Food Allergen Labeling and Consumer Protection Act


• Requires label disclosure of the 8 major allergens that cause 90% of all food allergies



2010 The most recent annual report of the American Association of Poison Control Centers

• Published in the journal Clinical Toxicology

• Reports zero reports of accidental deaths from dietary supplements



     Full implementation of mandatory federal cGMPs was completed in June

• All manufacturers & suppliers are now bound by FDA standards of safety and documentation



     The Dietary Supplement Full Implementation and Enforcement Act

• Introduced in Congress to increase funding for FDA enforcement of dietary supplement laws



     The Food Safety bill

• Includes enhanced mandatory recall authority for all foods, including dietary supplements

• Expected to pass Congress soon

Folic Acid: Risks or Myths?

There are theoretical risks for isolated folic acid in high doses. But these supposed risks fly in the face of established science and are controversial, not at all conclusive. There is also confusion over the significance of the supposed risks of high dose isolated folic acid in test tube and animal studies which do not identify a danger for moderate level supplementation - or even higher dose supplementation if combined with multivitamins or vitamin B-12. In other words, if the theoretical risks do not reflect real world human activities and the way that people actually obtain essential vitamins from their diet, including supplementation, aren’t these improbable risks really irrelevant to us? On the other hand, these negative reports may stop people from taking essential vitamins in quite reasonable amounts even though they are known to promote human health. Published human clinical science has determined that folic acid can reduce birth defects and has been proven to do so. Clinical science has also found mechanisms by which folic acid can prevent cancers, as well as the theoretical possibility that very high doses given in isolation can stimulate colorectal cancers including prostate cancer. There is stronger evidence that taking B-12 or a multivitamin along with high folic acid actually reduces rates of prostate and colon cancers. For example, in one human clinical trial where food intake, blood and plasma levels of folic acid were considered, Multivitamin users had about 2/3 the risk of subsequent prostate cancer as Non-Multivitamin users; only the independent use of folic acid was considered a risk factor. The report concluded, “…on the whole, the biological and epidemiological evidence supports the potential for folate supplementation to prevent colorectal neoplasia in humans.” (Cole) This shows that single nutrient studies, especially if unpublished and not peer reviewed or subjected to subsequent comments by experts in the field, should not be given overinflated importance when they are merely preliminary studies that may conflict with more relevant published human clinical studies. In the case of such conflicts, the human clinicals should bear more weight and be seen as more convincing, especially those that mimic the full range of variables (nutrients) in the human diet. Folic acid itself is considered non-toxic. Also, “data from in vitro and in vivo studies indicate that folic acid is not genotoxic [damaging to genetic material]”. (UK Food Standards Agency) There have been reports of levels as high as 50,000 micrograms per day given with no signs of toxicity in humans. There are accepted problems associated with levels exceeding 5,000 micrograms a day, which resulted in a far more conservative Upper Limit of 1,000 micrograms daily being set. This effect has been demonstrated in patients suffering from pernicious anemia taken off of their successful medicine (vitamin B-12), which was replaced by 5,000 mcg/day of folic acid. The substitution of one vitamin for another was unsuccessful in treating pernicious anemia, but did mask some symptoms. This test – and a large safety margin - provided the rationale given for the current Upper Limit. But it does not logically imply danger to those who are not severely anemic and who obtain B-12 in adequate amounts. (Oakley) It is very uncommon for people to take folic acid singly in doses of thousands of micrograms daily, but this is the method which test tube and animal studies often use. Overemphasizing unproven cancer risks requires ignoring valid studies showing reductions of cancers by taking folic acid and multivitamins. Needlessly scaring people from taking their vitamins, which have in human clinical trials shown significant improvements in birth defect and cancer rates, is not helpful to our common goal of protecting public health. Neil E. Levin, CCN, DANLA QUOTES & REFERENCES: Dr. Gideon Koren, director of the Motherisk Program at the Hospital for Sick Children in Toronto , note that rates of birth defects such as spina bifida and cancers such as neuroblastoma have plummeted since folic acid supplementation was begun. He believes that the known benefits outweigh theoretical risks. "I think it is very important to remember that the scares about cancer are mostly from animal studies and laboratory studies, not from human experience," he says. "We are still awaiting to see such human experience." http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20090417/folic_acid_090418/20090419?hub=SciTech Health Canada recommends all women of childbearing age take 0.4 mg of folic acid a day, but says taking more than 1 mg a day of folic acid without the advice of a doctor is not recommended. "We continue to encourage all women who could become pregnant to take a daily supplement," the agency says on its website. "We caution against taking more than one multivitamin tablet a day, as excess amounts of certain vitamins can be toxic." http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20090417/folic_acid_090418/20090419?hub=SciTech “All women who could become pregnant should take a multivitamin containing 0.4 mg of Folic Acid every day. To help reduce the risk of NTDs, you should start taking the vitamin supplement at least three months before you get pregnant and continue through the first three months of your pregnancy. Talk to your health professional to find the supplement best for you…If you have had a previous pregnancy affected by an NTD or have a family history of this problem, see your doctor. You may be advised to take a higher dosage of Folic Acid. If you have diabetes, obesity or epilepsy, you may be at higher risk of having a baby with an NTD, and you should see your doctor before planning pregnancy… Do not take more than one daily dose of vitamin supplement as indicated on the product label. Increasing your dose of Folic Acid beyond 1 mg per day without the advice of a doctor is not recommended.” (Public Health Agency of Canada , 2/27/08; http://www.phac-aspc.gc.ca/fa-af/index-eng.php) The NIH’s Office of Dietary Supplement reports on the prevention of cancer with the use of supplemental folic acid as part of a multivitamin: “Over 88,000 women enrolled in the Nurses' Health Study who were free of cancer in 1980 were followed from 1980 through 1994. Researchers found that women ages 55 to 69 years in this study who took multivitamins containing folic acid for more than 15 years had a markedly lower risk of developing colon cancer.” (Giovannucci E, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med 1998;129:517-24; http://ods.od.nih.gov/factsheets/folate.asp) Cole BF, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. Polyp Prevention Study Group. JAMA. 2007 Jun 6;297(21):2351-9. PMID: 17551129 Figueiredo JC, et al. Folic acid and risk of prostate cancer: results from a randomized clinical trial. J Natl Cancer Inst. 2009 Mar 18;101(6):432-5. Epub 2009 Mar 10. PMID: 19276452 Folic Acid, CASRN: 59-30-3. NLM TOXNET Hazardous Substances Database accessed online 28 March, 2009. http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@na+folic+acid Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr; Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. N Engl J Med. 2006 Apr 13;354(15):1567-77. Epub 2006 Mar 12. Erratum in: N Engl J Med. 2006 Aug 17;355(7):746. PMID: 16531613 Oakley GP Jr. When will we eliminate folic acid-preventable spina bifida? Epidemiology. 2007 May;18(3):367-8. PMID: 17435446 http://www.food.gov.uk/multimedia/pdfs/evm_folicacid.pdf

Beta-carotene risks over-stated

Beta-carotene risks over-stated By Neil E. Levin, CCN, DANLA A recent journal article pointed out the widely-reported danger of smokers using beta-carotene, a natural source (provitamin) of vitamin A, as part of their multivitamins. 1 In this meta-analysis the researchers have neglected to consider pre-existing dietary and serum levels of this nutrient, making their claim to control by placebo inadequate to properly isolate this variable. In fact, this failure to determine the effects of beta-carotene at a dose-dependent plasma level – and by neglecting to measure total beta-carotene intake along with the relevant synergistic antioxidants associated with it, as opposed to simply measuring supplemental intake - raises serious questions about the validity of these results. 2 There is also legitimate scientific debate over the use of trans versus cis forms of this provitamin that may affect the way it is used in vivo that dispute whether all forms are equal, which most studies simply do not address (including this meta-analysis). 3 Regarding beta-carotene safety little has been satisfactorily resolved, and the negative studies have been vigorously disputed for these and other reasons. For example, researchers have previously noted in the Journal of the National Cancer Institute that beta-carotene has been shown to not affect the risk of oxidative DNA damage in male smokers, despite its reputation as an antioxidant. But neither did the provitamin A prove to cause oxidative DNA damage. 4 It has become apparent to numerous observers that simply measuring supplementation of beta-carotene is not a good predictor of serum levels or of risk, and that a low level of total antioxidant intake may be a more valid marker in this regard. In fact, the dietary level of several antioxidants has been shown to be an independent predictor of plasma beta-carotene, especially in moderate alcohol drinkers. A recent study reports, “This may explain, at least in part, the inverse relationship observed between plasma beta-carotene and risk of chronic diseases associated to high levels of oxidative stress (i.e., diabetes and CVD), as well as the failure of beta-carotene supplements alone in reducing such risk.” 2 As the authors (Tanvetyanon, et al) of this current analysis have themselves noted, the Physicians Health Study compared the effects of taking 50 mg of supplemental beta-carotene (over 83,000 IU) every other day to a placebo in 22,071 US male physicians aged 40-84 and found no adverse health effects over a 12-year study period. 5 Likewise, the Women’s Health Study of 39,876 health professionals found no significant difference on lung cancer rates when looking at the effects of 50 mg of beta-carotene administered on alternate days over 2+ years plus a 4 year follow up period, using forms and dosing similar to the Physician’s Health Study to achieve very high serum levels of beta-carotene. 6 In a third study used in the current meta-analysis, The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group (ATBC), an antioxidant study in Finland was halted early because of a widely reported small increase in cancer rates among male smokers taking beta-carotene that were only possibly linked to that nutrient. 7 Headlines associated this supplement with cancer risk. Despite objections that the study was flawed, beta-carotene use dropped. This study continues to be widely cited and believed, despite the researchers’ own statements that the results were most likely due to chance. A later analysis published in July 2004 took another look at that same Finnish smokers study’s data, but now taking into account total antioxidant intake, which should have cleared away some of the scientific controversy over beta-carotene. The smokers’ risk of getting lung cancer was inversely associated with total antioxidants in the diet, with more total antioxidants resulting in fewer cancers. 8 In this study a composite antioxidant index was generated for each of the 27,000 men over 14 years. The calculated amounts of carotenoids, flavonoids, vitamin E, selenium and Vitamin C were compared to actual lung cancer rates, with a clear result: a combination of antioxidants lowered lung cancer risk in male smokers. Properly reviewed, beta-carotene was not the culprit; low antioxidant status was the more relevant factor affecting cancer rates, and supplementation with a single antioxidant supplement simply failed to create enough improvement to avert deaths related to oxidative factors. Perhaps the supplementation with beta-carotene was simply a case of “too little, too late”, rather than a root cause of a slightly higher lung cancer rate in those smokers. It is notable that Tanvetyanon et al included the ATBC study but failed to even reference the later Wright et al study that largely refuted the alleged harms of beta-carotene shown in ATBC, which were shown to be more likely due to low levels of total antioxidant intake than to excessive beta-carotene intake. This later review of ATBC should be a cautionary tale concerning the lack of proper controls in nutrient studies, especially as compounded by the use of meta-analysis, and should have alerted the current authors to that all-too-common mistake in nutrient study design. Indeed, another large study has noted that high carotenoid intake, confirmed by measures of plasma, was associated with lower mortality rates among the elderly over a ten year period. 9 This model measured results of consuming both supplements and foods, not solely supplement input, and when combined with plasma levels should therefore be regarded as a far more robust type of science for measuring vitamin effects than a meta-analysis of simply supplementation. As in the long-term Physicians Health Study, there was no observable risk of lung cancer noted in this report. The fourth study used in the current meta-analysis used very high doses of both beta-carotene (30 mg, equal to 50,000 IU) plus 25,000 IU of pre-formed vitamin A. 10 These amounts are extremely high; the Upper Limit for vitamin A is 10,000 IU, though there is none for beta-carotene because of its historic safety record. The amount of beta-carotene used in the eye vitamins were high only because the authors selected solely formulas designed for eye health that typically provide more beta-carotene than ordinary multivitamins. This distinction is not clear in their calling such formulas “multivitamins”, because that name is typically given to full-spectrum formulas containing a full range of the essential vitamins with minerals, not system-specific formulas like those sold for eye health. Such formulas have proved to be beneficial in maintaining eye health and the combination of antioxidants have been stronger antioxidants than beta-carotene, which is potentially a pro-oxidant at times and could thus be used more safely – and effectively - in combination with other antioxidants. 11 Most importantly, the authors have not shown why they assume that “multivitamin” use would be associated with the supposed risks of beta-carotene used singly, even if those risks for the solo provitamin are assumed to be true. Nor have they adequately demonstrated the alleged dangers of taking eye formula supplements, or even the danger of lung cancer rates increasing in those taking mixtures of beta-carotene combined with other antioxidant nutrients. In the case of multivitamins most studies have shown overwhelmingly positive effects, such as one report evidencing reduced infections in nursing homes with vitamins over placebo (73% vs. 43%; P < 0.001). Intervention was with a multivitamin containing beta-carotene. Infection-related absenteeism was higher in the placebo group than in the treatment group (57% vs. 21%; P < 0.001). Perhaps most importantly, 93% of participants with diabetes mellitus reported an infection versus only 17% of those receiving supplements (P < 0.001). 12 These huge reductions in potentially serious infections among our elderly citizens should be measured against the relatively slight and mostly theoretical risk of increased lung cancer rates associated with beta-carotene supplementation. A study reported in the Journal of the National Cancer Institute looked at death rates in a population given multivitamins or other nutrients. 13 After supplements were given for 5.25 years in the general population trial of 30,000 people, significant reductions in total [relative risk (RR) = 0.91] and cancer (RR = 0.87) mortality were observed in subjects receiving beta-carotene, alpha-tocopherol, and selenium combined. The same researchers reported on a subgroup of 3,318 persons with esophageal Dysplasia (a precursor to esophageal cancer) that was given either a multiple vitamin-and-mineral supplement or a placebo for 6 years. In this portion of the trial, small reductions in total (RR 0.93) and cancer (RR = 0.96) mortality were observed but were not significant. In any case, no increase in cancer rates was noted in the group taking multivitamins; there was actually a possible small benefit in terms of reducing this risk. The participants getting the multivitamin took a daily beta-carotene capsule along with two multivitamin tablets. This was a group of subjects at high risk of getting throat cancer. 14-15 It is a leap of faith to assume that a single nutrient would have identical effects to a combination of nutrients without substantial supporting evidence, which is still lacking; confounded by conflicting evidence and multiplying variables in meta-analyses. Since nutrients are both synergistic and present in the diet, it is important to factor those known variables into a proper study design. All too often, researchers do not consider this fundamental difference between drug and nutrient research and unwittingly introduce extra variables that undermine their conclusions. 16 This current meta-analysis of 4 studies - only one of which unquestionably shows a slight increase in lung cancer risk but does not actually measure isolated beta-carotene risk; two others are well-designed and robust studies looking at serum levels of those taking a high dose of beta-carotene but show no increased risk in lung cancer rates, and the fourth has been largely shown to be moot by a later and more complete re-analysis of the data - does not support the hypothesis that beta-carotene increases rates of lung cancer and that multivitamins are therefore dangerous. 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