Sunday, January 31, 2010

Is Centrum toxic?

Is Centrum Toxic?
By Susan G. Wynn, DVM and Heather Vogl, DVM

I formulate a lot of homemade diets and a source of vitamins and minerals, usually as a multivitamin, is critical to prevent deficiencies. My default multi is Centrum for two reasons: 1. it has a nice balance of vitamins and minerals without too much of any and 2. it is obtainable all over the country in small towns and large ones.

Occasionally I get complaints because someone wants a 'healthier' multi and while it usually results in a much more complicated diet, I can do use those. I can't argue with this inclination as I, too, prefer a whole food-extracted multi rather than a synthetic, but there is no proof that one is better than the other. The synthetic vitamins and minerals are well absorbed and can fulfill the needs for these essential nutrients. The complaints I've gotten are apparently based on one website:

The author of the website (which was apparently written in 2006 and has not been updated since) uses a few techniques to scare readers. For every ingredient, the manufacture is described in detail, apparently to scare readers with unfamiliar chemical names. The author consistently claims that inorganic forms of minerals are toxic and inappropriately active in the body, but these claims are not referenced. The toxicity studies cited in general describe trials where very high doses were used, rather than normal dietary doses. The circumstances are often different as well, quoting epidemiologic studies reporting widespread environmental contamination.

It also is not a critical review, as references cited are selected to show the author's bias, and do not analyze the literature as a whole or even fairly describe study conclusions (look at calcium carbonate, below, for instance). Finally, the site is completely anonymous - even the "about us" page lends no clue as to who the author is and whether they work for other companies or have some similar conflict of interest, or even knowledge enough to interpret the data quoted.

Below are specific analyses of the author's claims.

Magnesium Oxide is claimed to be "biologically inactive, and is not found in this form in foods". Magnesium Oxide can cause a pronounced laxative effect in higher amounts...(how does it have a laxative effect if it is biologically inactive?). The Hazardous Substances Data Bank (HSDB) cited refers almost entirely to toxicity from inhaling particles of magnesium oxide. The toxic dose for an adult human is stated by the Hazardous Substances Dtabase as "0.5-5 G/KG, BETWEEN 1 OZ OR 1 PINT (OR 1 LB) FOR 70 KG PERSON (150 LB)". That's a minimum of 35,000mg. Centrum contains 50mg. Our conclusion: logical inconsistency, lack of supporting references, dishonest representation of toxicity study.

Potassium chloride is stated to have "one of the highest salt index ratings (116) among commercial fertilizers and can cause injury to plants which is known as "burning." (so does table salt and dog urine). The site says "Potassium toxicity involves the following symptoms: gastrointestinal distress, e.g. nausea, vomiting, abdmoninal discomfort and diarrhea." (prunes can have the same effect). People with kidney problems should be especially careful when ingesting potassium that is not from a food source.(actually, Noni juice has caused toxicity in this group of people as well). Come on people - potassium chloride is *salt substitute* which is sold as a condiment. People can eat 2000-3000 mg/day of this stuff. Centrum contains 80mg. Our conclusion: logical inconsistency, lack of supporting references.

Microcrystalline cellulose - this is what the website has to say “The safety of ingesting this synthetically produced chemical has not yet been unequivocally determined. We do not yet know if it is a carcinogen, ground water contaminant, has developmental or reproductive toxicity, or is an endocrine disruptor. Nonetheless, evidence exists that it is toxic in mammals.(intravenous application of microcrystalline cellulose (MCC), in a dose of 5 mg/kg twice weekly for 10 weeks,1979)”. The study quoted is the only one apparently published, and the experimental design was based on administering microcrystalline cellulose intravenously at a high dose. The equivalent dose for a human of normal weight is 350 mg. There is no listed amount on Centrum, but it cannot contain more than about 30mg if you calculate the weights of the other components in each tablet. Our conclusion: logical inconsistency, lack of supporting references, dishonest representation of toxicity study.

Ascorbic Acid: The site says “although not known to be directly toxic, there is growing evidence that ascorbic acid causes a mild physical dependency, whereby removal of this chemical causes vitamin c levels in the blood to drop below baseline. Its use has also been correlated with increased incidence of kidney stones, and may be indicated in other problems caused by calcification of soft tissue.” (no references given). The development of oxalate stones may be increased with ANY form of vitamin C. I don’t even know how to evaluate the ‘mild physical dependency claim’ since no reference is given. Our conclusion: logical inconsistency, lack of supporting references.

Ferrous fumarate is inorganic iron. The website claims that it is “pro-oxidative, stimulating the damaging effects in the body of substances known as free radicals.(1) There is evidence linking high inorganic iron intake to cardiovascular disease and cancer. Excessive iron accumulates in the liver, and may feed bacterial and viral infection.”. The studies cited used 120 mg of ferrous fumarate in people with Crohn’s disease and inflammatory bowel disease. The Crohn’s paper actually states in the discussion that these patients probably absorb more iron due to their deficiency status and possibly the state of the gut itself. Centrum contains less than half the amount used in those studies. From the Wikipedia link on page: Humans experience iron toxicity above 20 milligrams of iron for every kilogram of mass (that would be 1400 mg daily), and 60 milligrams per kilogram is considered a lethal dose. Overconsumption of iron in children is usually due to eating large quantities of ferrous sulfate tablets intended for adult consumption, which is a preventable toxicity. The Dietary Reference Intake (DRI) lists the Tolerable Upper Intake Level (UL) for adults as 45 mg/day. For children under fourteen years old the UL is 40 mg/day. Centrum appears to contain exactly the amount of elemental iron required by menstruating women (L Hallberg and L Rossander-Hulten. Iron requirements in menstruating women. American Journal of Clinical Nutrition, Vol 54, 1047-1058). Our conclusion: logical inconsistency, lack of supporting references, dishonest representation of toxicity study.

Calcium carbonate - the site claims “risk factors associated with inorganic calcium ingestion, i.e. calcification of soft tissue, osteoarthritis, constipation, kidney stones, hypertension and various other side effects of poorly utilized calcium. Lancet and the British Medical Journal, recently published the results of two extensive clinical trails [sic] which concluded that calcium plus Vitamin D does nothing to prevent bone loss”. Actually, these studies note that calcium/D3 DOES benefit bone mineral density and that other studies show that it does prevent fractures.... both new studies had significant compliance concerns, with only 60 percent of respondents taking their supplements more than 80 percent of the time by the two-year mark. Our conclusion: logical inconsistency, lack of supporting references, dishonest representation of toxicity study.

dl-Tocopherol is biologically unprecedented and may have adverse side effects. New research demonstrates that taking only 1 member of the E family, which includes 4 tocopherols (alpha, beta, gamma, delta tocopherols) and 4 tocotrienols (alpha, beta, delta, gamma tocotrienols), may cause a deficiency of the other members. It is believed that the ingestion of dl-alpha tocopheryl in isolation may cause a deficiency of the heart-protective form known as gamma tocopheryl, hence adversely effecting the functioning of the heart.” Our conclusion: lack of supporting references.

Ascorbyl Palmitate - The site’s evidence for toxicity includes a link to one in-vitro study (enhanced uv damage in keratinocytes) and a lab animal study on bladder stones and retarded growth. (For every in vitro study suggesting damage, there are multiples of that number suggesting a benefit from the antioxidant activity.). Our conclusion: logical inconsistency, dishonest representation of toxicity study.

BHT is claimed by the site to be “suspected to be mutagenic and carcinogenic. BHT has been banned for use in food in Japan (1958), Romania, Sweden and Australia. The US has barred it from being used in infant foods”. In a comprehensive review of toxicity studies done over the years, (Lanigan RS, Yamarik TA. Final report on the safety assessment of BHT(1). Int J Toxicol. 2002;21 Suppl 2:19-94), doses used on rats and mice ranged from 50mg/kg of BW to 1500mg/kg BW. Interestingly in some of those studies, the test animals lived longer than control animals. At any rate, the dose of BHT in centrum is a tiny fraction of 1 mg/kg BW. Our conclusion: lack of supporting references, dishonest reprentation of toxicity studies.

Chromic chloride – from the site: “Although trivalent chromium like Chromic Chloride is far less poisonous than the hexavalent form, it is definitely a toxic substance, known to exhibit genotoxic, mutagenic, teratrogenic (reproductive hazard) and is on the Hazardous Substance list. ( no reference given). Centrum contains 120 mcg (.12 millgrams) of chromic chloride, which according to Federal Drinking Water standards is above the 100 mcg per Liter limit for safe consumption”. The reference here is not given, so I don’t know if it refers to 100mcg of chromic chloride or 100mcg of elemental chromium (I suspect the latter). Human beings are supposed to drink 2 liters per day, resulting in a top dose of 200 mcg daily of elemental chromium. Centrum contains 35 mcg of elemental chromium, right in line with recommendations for adequate daily intake. Our conclusion: lack of supporting references.

Calcium stearate is stated as "may be toxic" with the following justification - "It is entirely synthetic, and does not occur in nature. No toxicological studies have been carried out on this substance to date." Our conclusion: lack of supporting references, completely made up ‘toxicity’ claim.

Crospovidone – “Very little research has been done on the toxicity of this biologically unprecedented synthetic, however, animal studies showed this substance was carcinogenic, caused inflammation, pneumonia, and other adverse effects”. I was unable to studies of oral toxicity on this compound – most reports were when surgical antiseptic solutions were used to lavage body cavities. Our conclusion: lack of supporting references.

Cupric oxide is said to be “ generally considered a toxic substance in its unbound form. Virtually all copper in the body is present as a component of copper proteins. Unbound or inorganic copper produces oxidative stress in the body, catalyzing highly reactive hydroxyl radicals. Centrum contains 2mg of cupric oxide, supposedly 100% of the RDA. And yet, Federal EPA drinking water standards consider anything above 1.3 mg per Liter to be a health risk” The site does not define whether they think Centrum contains 2 mg of cupric oxide or elemental copper, but Centrum actually contains 0.5 mg of elemental copper. The human water requirement is about 2 liters per day, making the safe upper limit for an adult human 2.6 mg/day. Our conclusion: logical inconsistency

Cyanocobalamin – “ human studies have reported allergic reactions to skin testing, and mice given 1.5-3 mg/kg body weight experienced convulsions, followed by cardiac and respiratory failure”. It is important to keep some perspective here – FOOD causes allergic reactions in many, many people, and the lab animal study used a low dose of 1.5 - 3 mg/kg of cobalamin, - the usual human dose is 0.006 mg/kg). The site also says that because “some people lack the proper enzyme to actively detoxify and convert cyanocobalamin, or are overwhelmed by the ingestion of too much cyanide, it can accumulate in the body resulting in toxicity”. This occurs at very high doses and in people with congenital abnormalities – and certainly not at the dose provided in Centrum. Our conclusion: logical inconsistency, dishonest representation of toxicity study.

FD&C Yellow 6 (Sunset Yellow) according to the site “has the capacity for inducing an allergic reaction. It is associated with ADD and ADHD. (no reference given) This colourant is prohibited as a food additive in Finland and Norway. According to Dr. Andrew Weil, ‘The chemicals used to create colour are energetic molecules, many of which are capable of interacting with and damaging DNA. Anything that deranges DNA can injure the immune system, accelerate aging, and increase the risk of cancer. Indeed, many synthetic food dyes once considered safe have turned out to be carcinogenic’." Remember, natural food items cause allergies. References were not provided here, but it is true that the European Food Safety agency is concerned about reports of Sunset Yellow causing hyperactivity in people. The recommended top daily dose is 1 mg/kg of body weight. The dose in Centrum is something less than 0.1mg/kg of body weight.

Hydroxylpropryl Methylcellulose is “used as an excipient in drugs and supplements like Centrum.There are no long term toxicological studies available on this synthetic substance”. And yet this site labels it as “may be toxic”. Our conclusion: lack of supporting references, completely made up ‘toxicity’ claim

Magnesium Borate is “may have adverse antibiotic action vis-a-vis intestinal flora”. Link given about ‘borates and their uses and toxicity’ is dead. Our conclusion: lack of supporting references.

Magnesium Stearate is “used to make large scale production tableting of supplements and drugs possible, this chemical excipient is produced through reacting sodium stearate with magnesium sulfate, in a way similar to the production of other hydrogenated oils (a component of the diet of most people). potentially dangerous substance whose Hazardous Substance Databank Number is: 664”. The link to non-human toxicity studies does not function. According to the MSDS form: Chronic Health Effects: This product has no known chronic effects. Repeated or prolong exposure to this compound is not known to aggravate medical conditions. Acute Health Effects: This product is not listed by NTP, IARC or regulated as a Carcinogen by OSHA. Our conclusion: lack of supporting references.

Manganese Sulfate/MnSO4H2O - According to this site: “Toxicological data indicates it is tumorigenic, mutagenic and teratogenic”. The conclusion of the study cited was actually: Under the conditions of these 2-year feed studies, there was no evidence of carcinogenic activity of manganese (II) sulfate monohydrate in male or female F344/N rats receiving 1,500, 5,000, or 15,000 ppm. There was equivocal evidence of carcinogenic activity of manganese (II) sulfate monohydrate in male and female B6C3F1 mice, based on the marginally increased incidences of thyroid gland follicular cell adenoma and the significantly increased incidences of follicular cell hyperplasia. The doses given to the test animals ranged from 60-7400mg/kg of body weight. Centrum contains a total of 2.3 mg of manganese, or about 0.03 mg/kg BW. Our conclusion: lack of supporting references, dishonest representation of toxicity study.

Nicotinic Acid (Niacinamide) - According to this site: “large doses are known to cause liver problems as severe as liver failure.“ Nicotine has a half-life of about 60 minutes, and the liver is equipped to break down remaining amounts of nicotine. The toxic dose of niacinamide is 3000mg/day (M. Knip, I. F. Douek, W. P. T. Moore, H. A. Gillmor, A. E. M. McLean, P. J. Bingley, E. A. M. Gale and for the ENDIT Group. Safety of high-dose nicotinamide: a review. Diabetologia 2000; 43 (11): 1337–45.). The dose in Centrum is 20mg. Our conclusion: lack of supporting references, dishonest representation of toxicity study.

Nickelous Sulfate is described thusly: “classified within the National LIbrary of Medicine's "Hazardous Substances Data Base" (HSDB) as an animal and human carcinogen. It is classified by the National Institute for
Occupational Safety and Health (NIOSH) as "immediately dangerous to Life and Health," and a potential occupational carcinogen.” One link cited does not work, and the other supplied link states: An increase in mortality was not observed in chronic studies in rats or dogs fed nickel sulfate in the diet at doses up to 188 mg/kg/day for rats and 62.5 mg/kg/day for dogs (Ambrose et al. 1976). Centrum contains 5 micrograms (0.005 mg) per tablet per their website. Our conclusion: lack of supporting references, dishonest representation of toxicity study.

Polysorbate 80: “Polysorbate 80 is produced using ethylene oxide (which is known to cause cancer in rats). “ The issue here is the polysorbate, not the ethylene oxide. Polysorbate is used in ice cream to maintain its consistency, and IV medications such as amiodarone to keep them in proper form for administration. According to a study in the periodical Reproductive Toxicity, In Europe and America people eat about 0.1 grams of polysorbate 80 in foods per day. The study cited is a test tube study, which has no relevance to a living system. Our conclusion: lack of supporting references, dishonest representation of toxicity study.

Potassium Iodide “Chronic overexposure can have adverse effects on the thyroid”. The very study cited concludes : The results of our studies suggest that excess KI has a thyroid tumor-promoting effect, but KI per se does not induce thyroid tumors in rats. In this study, the intake of potassium bromide was 55 mg/kg of body weight daily. The dose in Centrum is about 0.3 mg (providing 0.15 mg iodine), or 0.004 mg/kg of body weight. Our conclusion: lack of supporting references, dishonest representation of toxicity study.

Pyridoxidine Hydrochloride (B6). Site states: “Extremely large doses in range of 2 to 6 g/kg (2000-6000 mg/kg) produce convulsions & death in rats and mice. Lower doses (50mg injections) have interfered with the endocrine system of rats by suppressing pituitary secretions.” The lowest dose here is about 25-30 mg/ kg of body weight. The total dose in Centrum is 2 mg, or 0.03 mg/kg of body weight in a person. Our conclusion: lack of supporting references, dishonest representation of toxicity study.

Silicon Dioxide - Site states: “ Although this chemical is known to have extensive acute, subchronic and chronic toxicities in animal studies, silicon dioxide is considered an acceptable food additive by the FDA.” Silicon is a vital trace mineral found in many foods. The author states This is primarily because of a lack of understanding the difference between silica found in food, or mammalian tissues, and inorganic forms. The qualitative difference is profound, and though theelemental silica content may be the same in a chard of glass and a piece of celery, the biological difference is as profound as the difference between life and death.” There isn’t a single supporting bit of science for this claim. Our conclusion: lack of supporting references.

Sodium Aluminum Silicate. Site claims “known to be a neurotoxin for over 100 years, and today it is known to be a major causative factor in diseases like Alzheimers.” No source is cited. Nobody knows what causes Alzheimer's. The Material Safety Data Sheet states that this chemical is only a mild skin irritant and if inhaled fresh air should be breathed.

Sodium ascorbate – the site states: “sodium ascorbate may affect genetic material (mutagenic) based on animal tests”. The link provided on the site clearly states: Ascorbic Acid and Sodium Ascorbate were not genotoxic in several bacterial and mammalian test systems, consistent with the antioxidant properties of these chemicals. Our conclusion: lack of supporting references, dishonest representation of toxicity study.

Sodium Benzoate – the site states: “Sodium benzoate is a synthetic preservative which has been shown to have an antibiotic effect on the essential friendly gut flora. The link provided on the site states: Benzoic acid is produced by many plants as an intermediate in the formation of other compounds (Goodwin, 1976). High concentrations are found in certain berries (see section 6.1). Benzoic acid has also been detected in animals. Benzoic acid (chemically equivalent) therefore occurs naturally in many foods, including milk products (Sieber et al., 1989, 1990). Sodium benzoate IS toxic to cats, at doses of at least 50mg/kg. It is AAFCO-approved at 14mg/kg (0.1% of the diet). The dose in Centrum is less than 10mg total, or 2mg/kg for a cat (0.15mg/kg for people). Our conclusion: lack of supporting references, dishonest representation of toxicity study.

Sodium Borate - the site states: “Definitely toxic” but does not supply a reference. MSDS information: Acute oral toxicity (LD50): 2.66 mg/kg [Rat.]. Acute Toxic Effects on Humans: Ingestion of 5-10 grams has produced severe vomiting, diarrhea, shock and death. Chronic Effects on Humans: Not available. That is a huge amount compared to the amount in Centrum (<2% of tablet per label). And I cannot find it in the ingredient listing in Centrum anyway. Our conclusion: lack of supporting references, dishonest representation of toxicity study.

Sodium Citrate – the site states: May be toxic with no source cited. “an unhealthy liver may have difficulty with this substance potentially resulting in an accumulation of bicarbonate (the metabolic derivative of citrate) which can cause metabolic alkalosis.” The MSDS states that topical contact is only slightly hazardous and to wash hands. Ingestion of large doses may well cause metabolic alkalosis, but Centrum contains less than 10mg total which is far from a dangerous dose. Our conclusion: lack of supporting references.

Sodium Metavanadate is stated to be “a form of vanadium with known toxicity when ingested or inhaled. It is a skin, eye and respiratory irritant.” In the study cited, the lowest dose given to geese and ducks was 10mg/kg of body weight. My calculations suggest (based on sodium metavanadate containing 42% elemental vanadium) is that Centrum contains 0.023 mg of sodium metavanadate, for heavens’ sake! Our conclusion: lack of supporting references, dishonest representation of toxicity study.

You know, I’m tired of doing this. I’ve spent 1 ½ days debunking the claims made here, and the author of this website is so consistently wrong that I’m not going to finish with the rest of the list.

So would I take Centrum? Yes, if I felt I really needed a basic multi and nothing else was available. But is Centrum toxic? Resoundingly no. Just another example of why you need to learn what constitute good information, and to check out claims made by Internet sites, your chiropractor and if you are really skeptical, your doctor or veterinarian.