Second Opinion on Herbs In a recent opinion, physician Henry I. Miller advocates a new way to regulate dietary supplements (DS), arguing that they are currently unregulated. Although a onetime FDA official and longtime industry critic, Dr. Miller seems out of touch with the current state of DS regulation, including recent major advances in quality assurance by manufacturers. His bias against natural products is made evident by his use of the slur “snake-oil” to dismiss herbal products as simultaneously ineffective and “dangerous”. Many observers, including FDA commissioners during congressional testimony, have testified that the agency has all of the authority it needs to regulate DS. Recent advances include the FDA’s current imposition of mandatory Good Manufacturing Practices (GMP), which was authorized by a 1994 law (DSHEA) that Dr. Miller inexplicitly claims exempted DS from government oversight. That same law stipulates that supplements must not be mislabeled or adulterated and the FDA has repeatedly taken action against such products, again proving Dr. Miller wrong. Manufacturers are now required to have procedures in place to assure product identity, potency and safety, as authorized by a law that Dr. Miller misrepresents. DS manufacturers supported a serious adverse event reporting (AER) law to track patterns of serious side effects. In the first year, the number of DS reports was significantly less than the FDA had predicted. An AER is casually linked to, but not proven to be caused by, a product. Dr. Miller’s assertion that foods and DS like herbs interfere with drugs (Miller’s ‘“real” medicines’) is telling. Is it professional bias to claim that foods, herbs and vitamins are unnecessary nuisances that are interfering with all-important medical treatment? In fact, these legendary interactions appear to be a minor issue. When the Mayo Clinic did a large patient survey to scientifically assess the risk, it reported that there were few such interactions, none serious, limited to only a handful of drug types and a few supplements such as garlic. Dr. Miller’s proposal for a new voluntary oversight entity for herbal products to correct a supposed lack of regulation is illogical; such entities already exist, and how could a voluntary program replace adequate regulation? His seeming ignorance of the current regulatory status of herbs is troubling, undercutting his rationale for such tinkering. Statistically, dietary supplements are safer than drugs and even safer than eating a meal, as recent AER reports prove. DS labeling and manufacturing are currently well-regulated. I suggest that studying drug-nutrient-herb interactions and addressing these on drug labels – where they belong - is a far wiser strategy than creating a “voluntary oversight” entity for dietary supplements, especially as there are already voluntarily GMP-certified brands available.
Tuesday, January 20, 2009
Saturday, January 03, 2009
More evidence that antioxidant “dangers” are exaggerated (especially beta-carotene) By Neil E. Levin, CCN, DANLA In a study published in 2006, cancer researchers tested daily supplementation of 400 IU of vitamins E as alpha-tocopherol along with 50,000 IU (39 mg) of beta-carotene on 540 head and neck cancer patients for three years after treatment with radiation therapies. Due to safety concerns in previous trials (which I have repeatedly criticized in previous writings, for various reasons), the beta-carotene component was discontinued during the trial. During a median 6 ½ years of follow up, 179 of the patients died. The researchers concluded that high-dose vitamin E supplementation could be harmful to cancer patients, with a 38% increased risk for death. 1 This study has been associated with the hyperbolic warnings against antioxidant use for cancer patients. The same group of researchers published a 2007 study looking at the same group of 540 cancer patients treated by radiation to see if the antioxidant vitamins reduced the toxicity of the treatments. This report investigated the dietary intake, supplementation and plasma levels of beta carotene in the patients to look for correlations in outcomes, specifically acute adverse effects of the radiation therapy and cancer recurrence. A higher beta carotene dietary intake was associated with 39% fewer severe acute adverse effects, and higher plasma levels with 27% fewer severe adverse effects, from the radiation treatments. The researchers reported that, “This study suggests that a higher usual dietary beta carotene intake can reduce the occurrence of severe adverse effects of radiation therapy and decrease local cancer recurrence.” 2 This conclusion is at odds with fears of beta-carotene toxicity that have been massively publicized over the past 14 years. Now, in 2008, we have heard again from this same group of researchers continuing to review the data from the same group of patients. It turns out that the large increase in mortality in the patient group given antioxidants - reported in the 2006 study – was basically limited to those patients who smoked during their radiation treatments. In fact, there was no significant mortality increase in patients who only smoked before or after the course of radiation treatment, or for non-smokers. 3 This new information tells us that the general cautions about antioxidants should be limited to certain narrow conditions or situations, such as active smokers during therapy. This is good information, since we know that 40% of cancer patients actually die of malnutrition; that plasma levels of antioxidants are a far better measure of antioxidant status than supplement intake prescriptions or dietary recall surveys; and that antioxidants are synergistic with inter-related functions and should not be given separately. Now we also can point to numerous benefits of antioxidants in clinical studies that have been far overshadowed by the over-hyped negative conclusions of a relative few prominent-but-flawed studies reported by prestigious institutions, sometimes with NIH funding. I agree with those critics who insist that it should be considered scientifically inappropriate to use the drug model for nutrient research, because the nutrients already exist in the diet and in the body and are clearly impacted by other nutrients; as well as other variables, some of which are quite well known. By contrast, in a drug study a new, foreign chemical is being tested which should not already be present in the diet or the body, making toxicity a bigger issue while eliminating many of the variables that are inappropriately ignored in sensational-but-flawed nutrient studies that get so much media attention and so many undeserved citations in scientific journals. I have previously written about the use of antioxidants for cancer patients, as have others, with the common conclusion that most such warnings are overblown and that much of the published science has been favorable regarding those combinations of factors. REFERENCES
- Bairati I, Meyer F, Jobin E, Gélinas M, Fortin A, Nabid A, Brochet F, Têtu B. Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients. Int J Cancer. 2006 Nov 1;119(9):2221-4. PMID: 16841333
- Meyer F, Bairati I, Jobin E, Gélinas M, Fortin A, Nabid A, Têtu B. Acute adverse effects of radiation therapy and local recurrence in relation to dietary and plasma beta carotene and alpha tocopherol in head and neck cancer patients. Nutr Cancer. 2007;59(1):29-35. PMID: 17927499
- Meyer F, Bairati I, Fortin A, Gélinas M, Nabid A, Brochet F, Têtu B. Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long-term effects on recurrence and mortality: a randomized trial among head and neck cancer patients. Int J Cancer. 2008 Apr 1;122(7):1679-83. PMID: 18059031
http://www.radiomartie.com/archives/2009.shtml Find me and listen at the link shown above. It will be posted this afternoon and available for listening as an archived program.
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. Thus, there is no sound basis in the current review for suggesting that warning labels may be needed for multivitamins or eye health supplements containing beta-carotene along with other nutrients that have been shown in well-designed studies to help protect the eyesight – and independence - of our aging population. REFERENCES: Tanvetyanon T, Bepler G. Beta-carotene in multivitamins and the possible risk of lung cancer among smokers versus former smokers: a meta-analysis and evaluation of national brands. Cancer. 2008 Jul 1;113(1):150-7. PMID: 18429004 Valtueña S, et al. The total antioxidant capacity of the diet is an independent predictor of plasma beta-carotene. Eur J Clin Nutr. 2007 Jan;61(1):69-76. Epub 2006 Jul 12. PMID: 16835597 [Supported by the European Community IST-2001–33204 'Healthy Market', the Italian Ministry of University and Research COFIN 2001 and the National Research Council CU01.00923.CT26 research projects.] Andreas Schieber, Reinhold Carle. Occurrence of carotenoid cis-isomers in food: Technological, analytical, and nutritional implications. Trends in Food Science & Technology, Volume 16, Issue 9, September 2005, Pages 416-422 van Poppel G, Poulsen H, Loft S, Verhagen H. No influence of beta carotene on oxidative DNA damage in male smokers. J Natl Cancer Inst. 1995 Feb 15;87(4):310-1. PMID: 7707423 Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med. 1996 May 2;334(18):1145-9. PMID: 8602179 Lee IM, Cook NR, Manson JE, Buring JE, Hennekens CH. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. J Natl Cancer Inst. 1999 Dec 15;91(24):2102-6. PMID: 10601381 The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med. 1994 Apr 14;330(15):1029-35. PMID: 8127329 Wright ME, et al. Development of a comprehensive dietary antioxidant index and application to lung cancer risk in a cohort of male smokers. Am J Epidemiol. 2004 Jul 1;160(1):68-76. PMID: 15229119 Buijsse B, et al. Plasma carotene and alpha-tocopherol in relation to 10-y all-cause and cause-specific mortality in European elderly: the Survey in Europe on Nutrition and the Elderly, a Concerted Action (SENECA). Am J Clin Nutr. 2005 Oct;82(4):879-86. PMID: 16210720 Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996;334:1150–1155. Bartlett H, Eperjesi F. Age-related macular degeneration and nutritional supplementation: a review of randomised controlled trials. Ophthalmic Physiol Opt. 2003 Sep;23(5):383-99. Review. PMID: 12950886 Liu BA, et al. Effect of multivitamin and mineral supplementation on episodes of infection in nursing home residents: a randomized, placebo-controlled study. J Am Geriatr Soc. 2007 Jan;55(1):35-42. Erratum in: J Am Geriatr Soc. 2007 Mar;55(3):478. PMID: 17233683 Blot WI, Li IY, Taylor PR, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 1993:8ı:1483-92 Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia. J Natl Cancer Inst. 1993 Sep 15;85(18):1492-8. PMID: 8360932 Blot WI, et al. The Linxian trials: mortality rates by vitamin-mineral intervention group. Am J Clin Nutr. 1995 Dec;62(6 Suppl):1424S-1426S. PMID: 7495242
Single antioxidants have far less power than mixtures of synergistic dietary nutrients, and both dietary and supplemental antioxidants should be considered to determine total antioxidant status before undertaking a well-designed clinical trial. Even the ability of most animals to synthesize their own vitamin C, which is not possible in humans, guinea pigs and some fruit-eating bats, affects one’s antioxidant status. The failure of most nutrient/supplement trails to consider these additional and critical variables casts most such studies in doubt, and is undoubtedly responsible for the conflicting and confusing results of so-called “gold standard” studies that are tarnished by the common failure to consider both nutrient sources and how nutrients interact. But that’s what happens when drug researchers attempt to study nutrients in the usual manner that they successfully use for pharmaceutical drugs. They simply do not understand or consider the additional variables, do not measure them or screen for them as variables, and thus fail to reach valid conclusions. Of course, the media parrots their triumphant press releases that nutrients are both dangerous and worthless. It makes me wonder why I bother to eat…
This link takes you to the website of the the Centers for Disease Control and Prevention (CDC): http://www.cdc.gov/vaccines/vac-gen/additives.htm "Common substances found in vaccines include: Aluminum gels or salts of aluminum which are added as adjuvants to help the vaccine stimulate a better response to the vaccine. Adjuvants help promote an earlier, more potent response, and more persistent immune response to the vaccine. Antibiotics which are added to some vaccines to prevent the growth of germs (bacteria) during production and storage of the vaccine. Egg protein is found in influenza and yellow fever vaccines, which are prepared using chicken eggs. Ordinarily, persons who are able to eat eggs or egg products safely can receive these vaccines. Formaldehyde is used to inactivate bacterial products for toxoid vaccines, (these are vaccines that use an inactive bacterial toxin to produce immunity.) It is also used to kill unwanted viruses and bacteria that might contaminate the vaccine during production. Monosodium glutamate (MSG) and 2-phenoxy-ethanol which are used as stabilizers in a few vaccines to help the vaccine remain unchanged when the vaccine is exposed to heat, light, acidity, or humidity. Thimerosal is a mercury-containing preservative that is added to vials of vaccine that contain more than one dose to prevent contamination and growth of potentially harmful bacteria."
Cardiovascular Health By Neil E. Levin, CCN, DANLA For a healthy cardiovascular system it is important to get plenty of nutrients over the whole range. B-Vitamins, for example, help to produce energy and to control metabolic processing, including the one that results in excessive levels of the inflammatory compound homocysteine. Homocysteine is a greater risk factor for cardiovascular risk than total cholesterol level. Antioxidants support each other, and clinical research indicates that total antioxidant status is more important than a single level of a single antioxidant nutrient. Antioxidants protect cholesterol from oxidizing, and also protect arterial surfaces from being damaged, leading to plaque formation and cholesterol “patches”. Minerals are also useful for cholesterol metabolism - especially chromium - also calcium, copper, and possibly magnesium and selenium. With the recent stories about obese children – some with Type-2 “adult-onset” diabetes - and with kids getting heart attacks in their teens, there is a growing awareness that cardiovascular health issues are not limited to middle aged men. Recent reports also point to the increased risk for women after menopause or who are on hormone replacement drugs, hammering the point home that age and gender are no longer rigid dividers of people into cardiovascular risk groups. That’s not to say that everyone is aware of these cardiovascular risk factors, but the risk categories in terms of age have certainly broadened dramatically in recent years. We have seen an increasing number of college-aged young men be afflicted by cardiac events at sports or training events, with some dying. Still, the risks do not seem as immediate to young adults with their heightened sense of immortality, especially young men. By the time men hit their 40s, there is an increased awareness of cardiac risks that keeps increasing throughout their lives. The young are mostly oblivious to health risks unless some event creates the beginnings of awareness that they may be at risk, such as a close relative suffering a cardiac event at an early age or a health scare. Unfortunately, these events seem to be increasing. Genetics, sedentary lifestyles, poor diet and obesity all make people susceptible to vascular problems. The emergence of hemorrhoids or any hint of varicose veins should be obvious indications of cardiovascular weakness at any age. Obesity and lack of stamina are also good indicators. Family health history is another consideration that should affect awareness. Circulation depends on body movement/exercise and requires an unobstructed blood flow through flexible blood vessels that have structural integrity. Collagen, elastin and supporting nutrients (proline, lysine, Vitamin C, Pycnogenol®, rutin) help to strengthen these tissues, while certain herbs (cayenne, garlic, horse chestnut, prickly ash extract, hawthorn extract) help to improve blood flow. Smoking and stress narrow the blood vessels, increasing the risk of forming clots or obstructions. Certain amino acids in the diet (arginine, citrulline) support NO (nitric oxide) formation that dilates blood vessels to reduce blood pressure and enhance blood flow to the peripheries. The presence of these components and modulators in the diet help to maintain cardiovascular health and vascular integrity. People should be eating a variety of fruits and vegetables, along with whole grains, in order to provide nutrients essential to the integrity of blood vessels. Products include beta sistosterol, vitamin C, Vitamin E, chromium, garlic, guar gum, Guggul extract, tocotrienols, policosanol, vitamins B1, B6, folate, B12, iodine, magnesium, selenium, potassium, carnitine, ginger, cayenne, hawthorn extract, CoQ10, lipoic acid, homocysteine regulators (B6, B12, folate, TMG), Policosanol, Red Yeast Rice Extract (plain or with CoQ10, alpha lipoic acid and silymarin), prickly ash extract, horse chestnut extract, butcher’s broom extract, grape seed extract, Pycnogenol® and rutin. However, other products are also helpful for cardiovascular health including gamma and delta tocotrienols, amino acids (taurine, carnitine, lysine, proline), Nattokinase (fibrin enzyme for supporting the body’s control of clotting), fish oil, and lecithin. Remember, you must take care of your heart and cardiovascular system if you expect them to take care of you for a lifetime!