Yohimbine & Berberine Protect From Death Due to LPS Intoxication; BCAAs Inhibit Serotonin Metabolism & Cause Anxiety, Tryptophan but not SSRIs Help; Sweet Tea Leaves Are PPAR-G Antagonists & Battle High Lipid + Leptin Levels

Skip the fireworks invest the money in some quality ingredients for a fondue or whatever you like and invest the (often non-negligible) rest of the money in a gym membership for the next year.

Actually my figure of the week is 115,000,000 EUR (~152,000,000 US Dollar), which is the sum my fellow country men and women are about to waste on pyrotechnics this year. And a scientifically unconfirmed addition based on my personal observation: 90% of the worst offenders as far as spending money for fireworks goes are at least overweight. Would be interesting to see, if the use of pyrotechnics on New Years Eve is directly associated with fat mass...

I mean, it could be that they spent so much money on their fireworks that they feel they can only afford the junkfood of which everybody and his/her mama still tend to believe that it would be cheaper than buying fresh products and preparing your own food from those.

Ah, I am ranting. That's usually Carl Lanore's task, so I will better go on with the items I have compiled for the today's last installment of On Short Notice in the year 2012:
 

• Berberine + yohimbine - a synergistic duo to prevent LPS toxicity (Li. 2012) -- With all the recent hoopla about the gut microbiome, I suppose that I don't have to tell you what the acronym LPS stands for, right? Hmm... just to make sure it stands for lipopolysaccharide endotoxins which are produced by gram negative bacteria in your gut and are so "toxic" (in fact they cause profound inflammation) that they can be lethal at higher doses.
  
  

  

  Figure 1: Survival rates (%) after ALB/c mice LPS injection (Li. 2012)

  A group of Chinese scientists have now found that aside from berberine the anti-inflammatory effects of which have been known for quite some time now, yohimbine administered in a daily dose of 2mg/kg (human equivalent 0.16mg/kg) does add to the survival rate of berberine treated rodents (human equivalent 4mg/kg) that were injected intragastrically (so not directly into the blood) with a potentially lethal dosage of 20mg/kg LPS. What's more, taken on its own yohimbine is even more potent than the alkaloid that's found in such plants as Berberis aquifolium, Oregon grape, Berberis vulgaris, Berberis aristata, Hydrastis canadensis (goldenseal), Phellodendron amurense, Coptis chinensis and Tinospora cordifolia.
  
  The mechanism is mediated by the prevention of liver injury, an upregulating of IL-10 production (an anti-inflammatory cytokine), and related anti-inflammatory effects resulting from the suppression of phosphorylation of IkBa, JNK, ERK and IRF3 in macrophages.

• Chronic 9-week high BCAA diet impairs brain tryptophan levels and causes anxiety (Coppola. 2012) -- Scientists from the Duke University took another look at the BCAA-tryptophan depression connection, you may have read about in the context of my "Sugar Addicted or Just Stressed Out?" post from January 3, 2012.
  
  According to the results Anna Coppola and her colleagues are about to publish in the American Journal of Physiology  - Endocrinololgy and Metabolism the provision of a BCAA-enriched diet for 9 weeks leads to both reductions in brain tryptophan levels and an increased turnover of serotonin (5-HT) in rodent brains:
  

  

  Figure 2: Composition of low fat  (LF) and high fat (HF) diets with or without added BCAAs (left); effects on the ratio of tryptophan  to the molar sum of large neutral amino acids with and without supplemental  tryptophan in the drinking water and 5HT turnover in the brain (no supplemental trp, right; Coppola. 2012)

  Both groups (BCAA and non-BCAA) consumed about identical amounts of food as the rodents in the complementary (LF or HF) groups, which confirms that the BCAA content did not modify the taste of the chow or rendered it unpalatable (cannot have been cheap bulk powder then ;-). The reduction in both the availability of tryptophan as well as the increase in serotonin (5-HT) turnover in the brain must in fact have been a consequence of the added BCAAs and are most likely the root of the disrupted transport of tryptophan across the BBB in rats, leading to reduced exploratory behavior of rats in EPM testing, a sign of increased anxiety.

  "Recent studies demonstrating a strong  association between BCAA levels, obesity, and obesity-related metabolic disorders, when linked to the findings reported here, may help to explain the strong association between obesity and behavioral abnormalities, including depression and anxiety." (Coppola. 2012)

  

  As the slight differences between the high an low carb diets show, other nutrients can influence serotonin as well (read more)

  In this regard it is important to point out that these negative side effects were mostly reversible by the provision of 15 mg/100 ml tryptophan in the drinking water of the rodents, but were not alleviated by  the administration of the common serotonine reuptake inhibitor fluoxetine (at 10 mg/kg/day for four weeks).
  
  Bottom line: Isolation is not what you want if what your body has been build for is complex food. And while the single serving of BCAAs you may gulp down during or right before a workout, on the other hand, probably isn't going to harm you. The "I need BCAAs every 30min" approach to gaining muscle mass, may well turn you into a psychotic wrack if you follow it day in and day out for months or years - at least without chronically adding some l-tryptophan to the equation.

• Sweet tea leaves protect against obesity: Once more via PPAR-gamma blockade (Zhou. 2012) -- Actually this is probably not news to anyone out there with a degree in Traditional Chinese medicine. After all, Lithocarpus polystachyus Rehd.(Sweet Tea) is Chinese folkloric medicine that has always been used to treat obesity, diabetes, and hypertension in South China:
  

  "Previous experiments revealed that it contains plentiful bioactive flavonoids and polyphenolic compounds, e.g. phlorizin, trilobatin, 3-hydroxy-phlorizin, etc. These components have extensive pharmacological activities, such as anti-diabetes, memory improvement, anti-aging, inhibition of lipid peroxidation and the growth of human colon cancer cells, and so on." (Zhang. 2012)

  From a "scientific" perspective, however, the efficacy of this herbal medicine as an obesity treatment had still to be elucidated.

  

  Figure 4: Effects of oral gavage of 75 mg, 150 mg and 300 mg/kg of body weight/day of sweet tea extract or placebo (DIO) in conjunction with the 8 weeks on a obesogenic diet (Zhang. 2012)

  In this context it is yet worth mentioning that this study demonstrated for the first time that the aqueous dry leaves extract of Lithocarpus polystachyus Rehd. can potently reduce the worst metabolic side effects of obesity, such as the hypolipidemia, hypoleptinaemia and the degree of insulin resistance (FINS, HOMA-IR, cf. figure 3) what it does not answer, however, is whether the decline in PPAR-gamma is tissue specific, what exactly is behind the profound decline in leptin levels and whether or not lean rodents, let alone humans, who don't consume an obesogenic diet will see anywhere similar benefits.
  
  In other words, this is research in progress, but I suppose something you are going to hear more about at the Supppversity in 2013.

* * * * * *

Apropos hearing or rather reading more, I guess you will realize that you have reached the end of today's installment of On Short Notice which means that you will have to progress to the SuppVersity Facebook Wall if you want a second serving of news on...

• The history of vitamin A as a light sensor and beyond - actually a free full-text I guess those of you who like to "think paleo" may enjoy (read more)
• A paper on "good" and "bad" inflammation, where the author points out that soothing inflammation too much can lead to a reduction in energy expenditure and may therefore not be the king's road to getting rid of the last blubber (read more)
• The food-hitlist of young Americans - Featuring sugar, sugary drinks, sugary bakery, sugary ... as their main energy and carbohydrate sources... (read more)
• Problems with synthroid and generics that have surfaced in a recent study on their efficacy in the treatment of congenital hypothyrodism (read more)

as well as a handful of other news, which are already there or are going to be posted within the next hours. Have a great weekend, everyone! 

References

• Coppola A, Wenner BR, Ilkayeva O, Stevens RD, Maggioni M, Slotkin TA, Levin ED, Newgard CB. Branched-chain amino acids alter neurobehavioral function in rats. Am J Physiol Endocrinol Metab. 2012 Dec 18.
• Li H, Wang Y, Zhang H, Jia B, Wang D, et al. Yohimbine Enhances Protection of Berberine against LPS-Induced Mouse Lethality through Multiple Mechanisms. PLoS ONE. 2012; 7(12): e52863. 
• Zhou CJ, Huang S, Liu JQ, Qiu SQ, Xie FY, Song HP, Li YS, Hou SZ, Lai XP. Sweet tea leaves extract improves leptin resistance in diet-induced obese rats. J Ethnopharmacol. 2013 Jan 9;145(1):386-92.

True or False: "Washing Your Fruit and Veggies is Useless - You Can't Wash Away the Pesticides, Anyway!"

It's a good idea to wash your veggies, but this is not the most effective method. Bath them in warm water, don't wash them under the faucet.

Despite the fact that I had my reasons to end the SuppVersity "True or False" Series back in the day. The popularity of the corresponding articles that appear from time to time as SuppVersity Classics on Facebook does yet tell me that you won't be mad at me, if I revive it and try to tackle a statement I've overheard in one of those infamous gym conversations between two ladies on the cross-trainer: "I always wash those pepper extra thoroughly, you know... tomatoes are among the veggies with the highest amounts of pesticides on them." Answer lady two: "Ha, you don't really believe the pesticides are on the outside of the tomatoes only, do you? They are in the tomato. Washing them will at best remove some of the dirt on their skin!"

True or False: "It's useless to wash your peppers."

False - I was surprised, when I realized that the answer to this True or False item was much easier to find than I had thought. It took me a while, though, before I found a study that analyzed data from more than just one vegetable variety, but the basic answer,  i.e. "No, it's not useless to wash your peppers - quite the contrary!" popped up right in my first cursory database search.

Figure 1: Amount of ethylenebisdithiocarbamates and chlorpyrifos on selected vegetable (µg/kg) before and after washing; the figure above the bars indicate %-change from pre to post washing (Chavarri. 2004; Randhawa. 2007)

If you look at the data of two studies I selected more or less randomly (see Figure 1) you will yet see that the effectiveness of the "wash away the pesticide approach" depends on both, the type of vegetable and the type of pesticide. With a mean total endusulfan reduction of >20% it should however be absolutely obvious that not washing your veggies would be wreckless.

Table 1: Current European Union Maximum Residue Levels in mg/kg (Council Directives 76/895/EEC and 90/642/EEC, last revised in June 2004)

Artificially contamination ➫ standardization: The baseline pesticide level of the vegetables in the Chavarri study was achieved by spraying fresh produce from controlled plots with no previous pesticide applications with those pesticides farmers usually use in the EU. The reason should be obvious: standardization. Thus, the pesticide levels were within the contemporary EU limits (s. Table 1) - something you cannot necessarily expect from every product you buy in the supermarket.

I mean, I shouldn't have to tell you to that it's unquestionably healthy not to be exposed to the full load of 24µ/kg chlorpyrifos and 1,626µg/kg ethylenebisdithiocarbamates (both have carcinogenic effects in humans; cf. Houeto. 1995, Josephson. 2005), from the tomatoes - specifically in view of the fact that 5.% of the tomatoes that are sold in the EU exceed the contemporary pesticide limits (Nasreddine. 2002) and would thus contain way more of these hazardous substances to begin with.

Aprospos washing! How do you do that?

You don't know how to wash veggies? Well, I obviously can't tell you what the absolute optimal way is, but what I can tell you is how scientists washed the specimen that were used in the studies the data in Figure 1 is based on: They placed the veggies in a dish or a clean lavatory with warm tap water and cleaned them with "gentle rotations of the hand" (Randhawa. 2007), before they grapped a conventional paper towel and blotted them dry.

Figure 2:  Illustration of the processing steps in Chavarri et al. (2007).

That's similar to what you do? Great, and you know what, I would bet that's not the only similarity between yourself and the average scientist. Just like you, scientists don't eat all their veggies raw. Consequently, both Chavarri et al. as well as Randhawa et al. conducted additional analyses of the pesticide content of their veggies after the produce had been blanched (the peppers were roasted, not blanched), peeled, pureed (Chavarri. 2004; see Figure 1) and cooked or peeled and cooked (Randhawa. 2007), respectively.

Figure 3: Relative ethylenebisdithiocarbamates and total endosulfan levels (in % of baseline) after washing, peeling, blanching / cooking & co. (Chavarri. 2004; Randhawa. 2007)

As you can see in Figure 3, each of these processing steps lead to a further reduction of pesticides. For the initially highly intoxicated asparagus, for example, even the last traces of pesticides ended up in the cooking water. If you would now decide to recycle the water for a soup or whatever, all your efforts to rid yourself of the pesticide would have been in vein.

"Conventional vs. Organic is not about getting more, but about getting  less for your money" | more

Bottom line: Wash your damn veggies you lazy *****! If you still don't believe that it's well worth spending this inconvenient extra-minute it takes to prepare warm water (28-32 °C), put your foods in, scrub a little with your hand and then continue processing them, I'd suggest you take a look at a recent meta-analysis from Ghent University in which the authors dealt with the exact same question and conclude:

"Reduction of residue levels was indicated by blanching, boiling, canning, frying, juicing, peeling and washing of fruits and vegetables with an average response ratio ranging from 0.10 to 0.82." (Keikotlhaile. 2010)

References:

• Chavarri, M. J., Herrera, A., & Arino, A. (2005). The decrease in pesticides in fruit and vegetables during commercial processing. International journal of food science & technology, 40(2), 205-211. 
• Houeto, P., Bindoula, G., & Hoffman, J. R. (1995). Ethylenebisdithiocarbamates and ethylenethiourea: possible human health hazards. Environmental health perspectives, 103(6), 568.
• Keikotlhaile, B. M., Spanoghe, P., & Steurbaut, W. (2010). Effects of food processing on pesticide residues in fruits and vegetables: a meta-analysis approach. Food and Chemical Toxicology, 48(1), 1-6.
• Nasreddine, L., & Parent-Massin, D. (2002). Food contamination by metals and pesticides in the European Union. Should we worry?. Toxicology letters, 127(1), 29-41.
• Randhawa, M. A., Anjum, F. M., Asi, M. R., Butt, M. S., Ahmed, A., & Randhawa, M. S. (2007). Removal of endosulfan residues from vegetables by household processing. Journal of Scientific and Industrial Research, 66(10), 849.

Sucralose, Carcinogen or Sweet Relief? Part III: DNA Breaks + Drug & Hormone Interactions | Sucralose, White Death?

Fearmongering fake, or true biohazard. This is the life-or-death- question this last installment of the sucralose trilogy will have to answer.

It's time for the third and last installment of the SuppVersity sucralose review trilogy. Looking back at the list of issues in the first installment of this series, it appears as if the one thing that was still left to discuss are the mutagenic, pro-carcinogenic and tissue damaging effects of sucralose and its potentially endocrine disrupting metabolic / thermic byproducts. It goes without saying that the previously discussed and largely rebutted effects on blood glucose management, body weight gain and even the balance of your gut microbiome would be hardly significant, if today's analysis confirms that the use of Splenda© & Co was linked to direct mutagenic, carcinogenic or general toxic effects.

Put your hazard suits on, folks!

It's obvious that I got carried away by my imagination, when I wrote this subheading, but if the same wasn't true for the author of the repeatedly cited press release, many of us are about to suffer the consequences of the potential unsafety of the hitherto unknown sucralose metabolites in our guts, pretty soon.

This is part III of a multi-part series:

Sucralose, insulin, glucose, GLP-1

Appetite, Obesity & Gut Health

Cancer, Drug & Hormone Interact.

I know that Mark Sisson likes to says this, but this website is not written by a machine, but by a man who has the same "short" 24h days you have... basically, what I am trying to say is that I had to split this review of the review into a "trilogy" - and be honest, you wouldn't want an article thrice as long as this one, would you?

In fact, you don't even have to go searching the databases for hours to find evidence that would support the claim that some of these metabolits that supposedly arise, while sucralose passes through our digestive tract (hitherto we have only highly debated evidence from rodent studies that there are any metabolits at all, by the way) could be pretty nasty bastards. In their 2008 paper, Abou-Donia et al. (2008), whose rodent study is still the only one to support the claim that the consumption of sucralose (HED 42mg/day or more over 3 months) will lead to a "reduction in the number and balance of beneficial bacteria in the gastrointestinal tract" (quote from press release; learn more), cite a study, for example, in which Sasaki et al. (2002) confirmed that sucralose exerts genotoxic effects. This does not mean that the DNA breaks / changes the researchers observed lead to the development of cancer, but the in vivo comet essay the researchers used, is generally considered a very reliable indicator of the genotoxicity of the tested compound in a particular body part (Brendler-Schwaab. 2005).

Believe it or not, but aspartame is one out of three sweeteners Sasaki et al. tested that are not genotoxic | more about aspartame

It's not just sucralose: I guess it's only fair, if I point out that Sasaki's study showed that sodium cyclamate, saccharin, sodium saccharin, likewise artificial sweeteners, caused DNA damage to various organs, as well. The dosage that was necessary to trigger these effects was yet unrealistically high: 2000mg/kg for sucralose and sodium cyclamate, 1000mg/kg for saccharin and sodium saccharin - for humans that would be 26g and 13g of pure sweetener every day! Ah, before I forget to mention that: Acesulfame-K, aspartame and stevia were also tested and found to be benign.

The absence of direct evidence of real-world negative effects, the insignificance of the long-demonstrated weak muatgenicity in the mouse lymphoma mutation assay, both, the WHO and the FDA have confirm ed in independent reports (WHO, 1989; U.S. FDA, 1998), is thus probably the reason the compound has still been approved as a food additive in 1991 - initially in Canada and Australia, then in the rest of the federally regulated world (Canada & Australia, 1993; New Zealand, 1996; US, 1998; EU, 2004). Today, the sales in sucralose alone account for 27.9% of the $1.146 billion global highpotency sweetener market (Leatherhead Food Research, 2011). No wonder, after all, sucralose is utilized in thousands of food, beverage, and pharmaceutical products in North America, Latin America, Europe, the Middle East, and the Asia-Pacific region (Schiffman. 2013).

So what does the (almost) "real-world" evidence say?

It's unquestionably debatable whether this was a good idea or a tragic mistake, but without corresponding "real-world" assays from longer-term rodent studies, the damage that occurs in response to the DNA breaks that have been observed in in-vitro studies may well be so small that the DNA repair machinery that operates in our bodies 24/7 can fix it easily. In this case, our coroners would probably find a similar increase in non-neoplastic findings (=non-cancerous, often minimal tissue growth, where it does not belong), as they were reported by Mann et al. (see list below the red box) in a combined chronic toxicity/carcinogenicity study of sucralose in Sprague–Dawley rats and a carcinogenicity study of sucralose in mice (Mann. 2000a, 2000b). Direct evidence for the development of cancer and/or the potential epigenetic changes is yet, as Schiffman & Rother have to concede, simply not available.

Don't bake your arginine-containing anti-diabetes cookies with sucralose

Sucralose + heat - a potentially hazardous combination: Contrary to often cited claims by Barnd & Jackson (1990) or Miller, et al. (1999), there is more recent evidence that suggest sucralose is not heat stable (Jahn & Yaylayan. 2010; Schiffman. 2012; Schiffman and Abou-Donia. 2012). According to these more recent papers ther are a whole host of thermal degradation products in cookies. Whether these byproducts pose a health risk is however not know for most of them. Only the chloropropanols that form when the reaction occurs in the presence of gylcerol (Rahn. 2010), are well-known genotoxic, carcinogenic, and tumorigenic compounds (Biles. 1983; Cho. 2008; Tritscher. 2004; SCF. 2001; WHO, 2002).

Quite the contrary, if you look at the literature as a whole, there is plenty of data that would support the decision of the Australian, US and EU to approve sucralose as a food additive, e.g.:

• No toxic effects even with 3% of total dietary intake in Sprague–Dawley rats; all non-neoplastic findings that occurred were of no toxicological significance and are part of the regular aging process of this strain of rats (Mann. 2000a)
• No positive results in in vivo chromosome aberration test in rats and two separate micronucleus tests in mice with doses of up to 2,000mg/kg for 5 days (Brusick. 2010)
• No effect on organ and general development, when fed to pregnant rats and rabbits in HEDs of up to 26g (rats) and 9g, respectively (Kille. 2000)

I don't want to discard the existing evidence Schiffman et al. cite in favor of their "sucralose is the devil" hypothesis, but results of the vast majority of these studies can hardly be considered relevant with respect to the question whether the comparatively small amount of sucralose that may be present in your foods, supplements or whatever you may be sweetening with sucralose is going to harm you or your DNA:

• The death of one out of 10 mice in a study by Finn and Lord that occured in response to the ingestion of the human equivalent of 1g/day of sucralse can hardly be considered conclusive evidence in favor of the "sucralose is poison hypothesis (Finn. 2000).
• The effects Mann et al. describe in a study where 3%-5% of the chow was pure sucralose is devoid of any relevance for our question (Mann. 2000a; Goldsmith. 2000). The same goes for the numerous studies where the lab animals received sucralose in amounts of >500mg/kg body weight (e.g. Finn. 2000; Kille. 2000). For a human being that would be more than 6.5g/day - and that's only if the lab animal was a rodent. For larger animals it would be even more.

Now, you can always argue that the negative studies just weren't long enough to elicit similar effects at lower dosages or, if you prefer that, work yourself up into a lather about the fact that (conspiracy-)theoretical, all the benficial studies could have been openly funded or secretly supported by people / companies with a vested monetary interest in positive safety data. In fact, the existence of a review of the safety of Splenda the lead author of which works for McNeil Nutritionals, LLC, who market Splenda for Johnson & Johnson (Grotz. 2009), or a "expert panel" review you will read about later in this article actually support that this may be the case, the same can unfortunately be said of almost every food additive - including stevia, by the way.

Let's get on to potential endocrine effects

In view of the fact that it is pointless to speculate about the validity of the data from the positive studies in the foregoing list, I want to turn to another, the final and as we are going to see not necessarily more "productive" topic of this third and last installment of my sucralose review trilogy: The endocrine effects.

Due to sucralose not just vegans (more) may be at risk of low B12

Sucralose + Vitamin B12: This is not exactly an endocrine effect, but in the end it could become one, when large enough quantities of cobalamine, aka "vitamin B12" react with sucralose in the liver, vitamin B12 deficiency could be a potential side effect. Aside from the in-vitro evidence Motwani et al. present in their 2011 paper in Food and Chemical Toxicology, there is yet no evidence that would suggest that this is actually happening, let alone to an extent that would leave you B12 deficient like a vegan ;-)

In that, I am using the word "endocrine" in its most general sense, which denotes anything that is produced or directly triggered by an organ and has influence on other organs / tissues or the whole body. The sucralose induced changes in the expression of enzymes from the P450 cytochrome cascade that are responsible for the interconversion / metabolism of all sorts of molecules, including hormones and medications would be one example for such effects.

To this ends we have to go back to the previously cited study by Abou-Donia et al. (2008), of which I did not tell you in the last installment of this series that it has (obviously) been under heavy attack by toxicology experts who do not necessarily doubt the validity of the study data Abou-Donia et al. present, but claim that their interpretation was irresponsible.

A brief note on the criticism of the Abou-Donia study: As you'd expect it's no coincidence that  the corresponding paper carries the phrase "expert panel" in it's title. It was after all written and published on request of McNeil Nutritionals, a marketer of retail products that contain the non-nutritive sweetener, sucralose, who paid the "panel of experts" to do a "independent and rigorous review of the 2008 study by Abou-Donia et al." (Brusick. 2009)

I won't discuss all the objections the "expert panel" proffers. Not because I think that their general objections against hasty conclusions with respect to unwanted negative health effects weren't justified, but rather because I want to get back to Schiffner's & Rother's review, where you'll find the following comment about the CYP-modifiying effects Abou-Donia et al. observed and Brusick et al.'s criticism:

"The results in Table 1 [identical copy on the right] indicate that the magnitude of elevation for both CYP3A and CYP2D expression increased in a linear, dose-dependent manner as the dosage of sucralose increased from 3.3 to 5.5 to 11 mg/kg/d.

This finding of significant and parallel increases in expression of two different CYP enzymes does not support the claim made by Brusick et al. (2009) that increases in CYP from sucralose ingestion were only normal biological variations."(Schiffman. 2013)

In other words: Coincidental increases in CYP activity would not 'coincidentally' be dose-dependent, as well. If we also remind ourselves of the fact that the human equivalent doses of said 3.3, 5.5 and 11mg/kg sucralose would be (only) 43mg, 71mg and 143mg it is self-evident that we cannot simply ignore the acute and persistent increases in intestinal P-gp, CYP3A, and CYP2D (in humans this is CYP2D6; cf. Laurenzana. 1995) in the jejunum and ileum of About-Donia's hairy subjects.

The obvious question, now, is: Does this even matter?

I mean, changes in the expression of some cryptic enzymes in the gut - who cares? After taking a look a the list of substrates that are enzymatically processed by CYP3A, alone, even the small 44% increase that occured in response to the rodent equivalent of 43mg appears relevant.

Figure 1: Important supplement drug interactions | learn more

On this list are some immunosuppressants, many chemotherapeutics including tamoxifen and anastrazole, which are popular with athletes who use PEDs. There are SSRIs, like citalopram, norfluoxetine, sertraline, other anti-depressants like mirtazapine, or buspirone, the whole list of anti-psychotics, opoids and many analgesics, benzodiazepines, statins like atorvastatin, lovostatin and simvastatin, calcium channel blockers, anti-histamins and even viagra and Co (PDE-5 inhibitors). And even our good old caffeine is on the list of CYP3A4 substrates, on which you'll also find estrogen, testosterone, progesterone, finasteride and torimifene. It's thus not just that your chemotherapy may fail, your depression may return, you may run havoc, hurt all over, increase your cholesterol levels, get high blood pressure, have life-threatening allergic reactions, because your meds are not working properly no (!), even worse caffeine may stop working ;-)

Unlike the increase in CYP2D6 that simply adds to the sucralose ↔ drug interactions, the corresponding increase in P-gp activity and thus the transport of chemicals from gut cells (enterocytes), back into the intestinal lumen could affect the absorption of an even wider range of both wanted and unwanted chemicals / xenobiotics with a hydrophobic and amphiphilic structure.

The net result of the increases in CYP and pGP activity is thus a significant decrease in the concentration of a xenobiotic compound on its way from the gastro-intestinal tract to the liver. Whether this amplified "first pass effect" would actually have physiologically relevant consequences in human beings is yet something we cannot tell without somebody paying for the costly research.

To complicate things, we must not ignore the possibility that "[...t]he rise in CYP expression reported by Abou-Donia et al. (2008) may result from 'autoinduction', by which sucralose enhances it own metabolism." It would thus be a second St. John’s wort, which will also increase its own metabolism by the activation of P-gp and CYP. For Hypericum perforatum extracts, which are often used as mild anti-depressants, we do already know that it affects the metabolism of an endless list of drugs and herbal supplements, and can reduce the levels of 5-alpha reduced androgens like DHT (estrogen and testosterone appear not to be influenced, though; cf. Donovan. 2005).

So what about toxicity and endocrine disruption? If we discard the potential interference with drugs and consequent "St. John's Wort"-esque side effects, I would say that the dosages that are necessary to actively induce more or less insignificant DNA damage in rodent studies, as well as the absence of any evidence of toxic effects from one of the historical single-dose or short-term sucralose studies in humans (Mezitis. 1996; Baird. 2000) make it appear very improbable that the habitual, but reasonable use of sucralose could have toxic or carcinogenic effects.

Remember the Science Round-Up from March? The safety of  stevia, is not beyond doubt either | more

The "benefit of the doubt" is yet no acquittal, it is only my assessment of the reasoning Schiffman & Rother provide in their paper, the relevant parts of which are all based on mere hypothesis, e.g. the "IBD ↔ sucralose"-hypothesis by Qin et al. (2011, 2012), or the "there may arise different more toxic sucralose metabolites in the human vs. rat digestion tract"-hypothesis by Goldsmith (2000) and Mann (2000a) and/or rely on data from the highly disputed Abou-Donia study, the most significant result of which are (imho) still the pronounced changes in the gut microbiome (read more in the last episode of this three part series).

At the moment, it does yet still look as if you were on the "safer" side if you prefer stevia sweetened products, although I honestly have my doubts that we wouldn't observe similar effects in mice, rats and all sorts lab critters, if 5%+ of their diet was pure stevia. The dosage makes the poison, you better remember that.

References:

• Abou-Donia, M. B., El-Masry, E. M., Abdel-Rahman, A. A., McLendon, R. E., & Schiffman, S. S. (2008). Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. Journal of Toxicology and Environmental Health, Part A, 71(21), 1415-1429.
• Brendler-Schwaab, S., Hartmann, A., Pfuhler, S., & Speit, G. (2005). The in vivo comet assay: use and status in genotoxicity testing. Mutagenesis, 20(4), 245-254.
• Brusick, D., Grotz, V. L., Slesinski, R., Kruger, C. L., & Hayes, A. W. (2010). The absence of genotoxicity of sucralose. Food and Chemical Toxicology, 48(11), 3067-3072. 
• Brusick, D., Borzelleca, J. F., Gallo, M., Williams, G., Kille, J., Wallace Hayes, A., ... & Burks, W. (2009). Expert panel report on a study of Splenda in male rats. Regulatory Toxicology and Pharmacology, 55(1), 6-12.
• Biles, R. W., & Piper, C. E. (1983). Mutagenicity of chloropropanol in a genetic screening battery. Fundamental and Applied Toxicology, 3(1), 27-33.
• Cho, W. S., Han, B. S., Lee, H., Kim, C., Nam, K. T., Park, K., ... & Jang, D. D. (2008). Subchronic toxicity study of 3-monochloropropane-1, 2-diol administered by drinking water to B6C3F1 mice. Food and Chemical Toxicology, 46(5), 1666-1673.
• Finn, J. P., & Lord, G. H. (2000). Neurotoxicity studies on sucralose and its hydrolysis products with special reference to histopathologic and ultrastructural changes. Food and chemical toxicology, 38, 7-17.
• Goldsmith, L. A. (2000). Acute and subchronic toxicity of sucralose. Food and chemical toxicology, 38, 53-69.
• Grotz, V. L., & Munro, I. C. (2009). An overview of the safety of sucralose. Regulatory toxicology and pharmacology, 55(1), 1-5.
• Motwani, H. V., Qiu, S., Golding, B. T., Kylin, H., & Törnqvist, M. (2011). Cob (I) alamin reacts with sucralose to afford an alkylcobalamin: Relevance to in vivo cobalamin and sucralose interaction. Food and Chemical Toxicology, 49(4), 750-757.
• Kille, J. W., Tesh, J. M., McAnulty, P. A., Ross, F. W., Willoughby, C. R., Bailey, G. P., ... & Tesh, S. A. (2000). Sucralose: assessment of teratogenic potential in the rat and the rabbit. Food and chemical toxicology, 38, 43-52.
• Laurenzana, E. M., Sorrels, S. L., & Owens, S. M. (1995). Antipeptide antibodies targeted against specific regions of rat CYP2D1 and human CYP2D6. Drug metabolism and disposition, 23(2), 271-278.
• Leatherhead Food Research. (2011). The global food additives market, 5th ed., September.
  Leatherhead, Surrey, UK: Leatherhead.
• Mann, S. W., Yuschak, M. M., Amyes, S. J. G., Aughton, P., & Finn, J. P. (2000a). A combined chronic toxicity/carcinogenicity study of sucralose in Sprague–Dawley rats. Food and chemical toxicology, 38, 71-89.
• Mann, S. W., Yuschak, M. M., Amyes, S. J. G., Aughton, P., & Finn, J. P. (2000b). A carcinogenicity study of sucralose in the CD-1 mouse. Food and chemical toxicology, 38, 91-97.
• Rahn, A., & Yaylayan, V. A. (2010). Thermal degradation of sucralose and its potential in generating chloropropanols in the presence of glycerol. Food Chemistry, 118(1), 56-61.
• Sasaki, Y. F., Kawaguchi, S., Kamaya, A., Ohshita, M., Kabasawa, K., Iwama, K., ... & Tsuda, S. (2002). The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 519(1), 103-119. 
• Scientific Committee on Food. (2001). Opinion of the Scientific Committee on Food
  on 3-monochloro-propane-1,2-diol (3-MCPD). European Commission, Health and
  Consumer Protection Directorate-General. http://ec.europa.eu/food/fs/sc/scf/out91_en.
  pdf (accessed December 14, 2013)
• Tritscher, A. M. (2004). Human health risk assessment of processing-related compounds in food. Toxicology letters, 149(1), 177-186.
• World Health Organization. (2002). 3-Chloro-1,2-propanediol. In Safety evaluation of certain food additives and contaminants. WHO Food Additives Series 48. http:// www.inchem.org/documents/jecfa/jecmono/ v48je18.htm (accessed December 14, 2013).

Commercially Available Teas "Not Suitable For Human Consumption": Potentially Hazardous Amounts of Lead, Aluminum, Arsenic & Co in Every Cup

Would all commercially available teas have to be labeled like this?

I am usually not a fan of articles with titles like this one (see above) - they have what you call in Germany "Bildzeitungsniveau" (the German tabloid with news like "World about to disappear in a black hole, when CERN starts operating). It is however hard to resist the urge to use a headline like the one above, if the it fits the results of peer-reviewed scientific paper so well, as it is the case with the relatively recent paper from the University of Alberta and the Luleâ University of Technology in Sweden this SuppVersity article is (almost) all about.

The corresponding experiment, the results of which were published in the peer-reviewed open-access Journal of Toxicology in October 2013, already, addresses the increasing concern about contamination of foodstuffs and natural health products. With the emphasis being on foodstuff and health, it's only logical that tea, or more precisely all currently available off-the-shelf varieties of black, green, white, and oolong teas sold in tea bags were used for analysis in the said study.

So what did the researchers do?

Schwalfenberg, Genius (no joke, the 2n author is a real 'Genius by name') and Rodushkin conducted a three-step analysis in the course of which they analyzed the content of previously identified tea contaminants like aluminum, fluoride, mercury, lead, cadmium and arsenic (Fujimaki. 2004; Lung. 2008; Wang. 2008; Alvarez-Ayuso. 2011; Tan. 2012) in commercial tea preparations.

Table 1: There are not just bad, but also healthy minerals in tea!

Before we get to the "bad stuff", though, let's start with the positive findings of their investigation. The data in Table 1 is after all evidence enough that there are also "healthy" minerals in tea - the amount is not high enough to cover your RDA, but this does not mean that it could not be at least partly related to the undeniable health benefits researchers all around the world report for people who consume uncontaminated tea on a regular base. As a loyal SuppVersity readers you know most, if not all of them from previous articles on tea. The reason I still believe it's worth enumerating them again is that I don't want you to give up on your beloved (?) tea too easily - I mean, Coke is not an alternative and for coffee fungi and other stuff could make a similarly unhealthy "supplement" to your breakfast beverage:

• Cardiovascular benefits - When we are talking about health in general and heart health in particular, most people will think of green tea. That's pretty unfortunate, because there is ample research for all varieties of teas that they can lower blood lipids, provide "clean" and thus heart healthy energy, and exert antithrombotic and anti-hypertensive effects.
• Anticancer effects - Despite the fact that the anti-cancer effects have mostly observed in in-vitro studies, there is plenty of epidemiological evidence that tea drinkers have a lower cancer risk, than the average coke guzzler (not necessarily breast cancer, though ➫ SuppVersity Facebook News).
• Metabolic syndrome - While more recent studies clearly suggest that the active weight loss effects of tea, in general, and green tea, in particular, have been totally overblown, there is still a host of controlled trials, where adding tea (not necessarily green tea) improved the effects of a energy restricted diet. Compared to the rodent trials which are still fueling the myth of the potent thermogenic effects of (green) tea, the real world results in human beings are however downright disappointing.

• 

  A green tea marinade will keep your meats fresh | learn more

  Anti-infective properties - Only few people (SuppVersity readers included - of course) know that green tea can be used as a mouthwash and is currently researched as an anti-bacterial food additive by researchers all around the world. According to a paper by Steinmann et al. (2013), the anti-infective effects are mediated by the antiviral, antibacterial, and antifungal properties of Epigallocatechin gallate (EGCG). The same EGCG about which you've read only recently on the SuppVersity that it is not exactly as useful as a fat loss adjuvant, as the hype would have you believe.
• Other beneficial effects - Under "Miscellaneous Effects", Schwalfenberg et al. also list the nephropotective effects of green tea, which could come very handy if you guzzle mercury contaminated green tea, everyday (unfortunately, mercury is your least problem with tea), the anti-depressive researchers have observed in people consuming 4+ cups of tea per day and the hitherto unconfirmed hypothesis that tea drinkers are (better) protected against Alzheimer’s and neurological decline.

In view of these benefits it's only logical that the Canadian + Swedish research team chose to repeat  the dichotomous health effects of drinking tea in the title of their paper "The Benefits and Risks of Consuming Brewed Tea" (my emphasis in Schwalfenberg. 2013)

Organic is not better than regular tea

To obtain a dataset that would be as comprehensive, accurate and practically relevant as possible the authors bought 30 different organic and non-organic white, green, oolong, and black teas from the the shelves of Canadian supermarkets and analyzed (a) the "raw" tea leaves (LEAF), (b) tea that had been steeped for 3-4 minutes (3MIN), (c) tea that had been steeped for 15–17 minutes (15MIN).

Know your teas: As a SuppVersity reader you will probably know that all teas come from the same plant. It's the processing that determines if we call it "white", "green", or whatever else:

• White tea: young leaves or new growth buds, withered, uncured, baked dry 
• Green tea: steamed or dry cooking in hot pans to prevent oxidation; dried tea leaves may be separate leaves or rolled into pellets (gunpowder tea)
• Oolong tea: withering of leaves under sun and warm winds with further oxidation standard between green and black teas
• Black tea: leaves are completely oxidized, withered

Due to the processing of the leaves tea from the same camellia sinensis plant can contain different amounts of contaminants depending on whether you buy it as white, green, oolong or black tea, or shredded green tea supplement.

Still, the main determinant is and remains the soil it was grown on (see Table 4)?

All tea samples underwent the same standardized procedures before they were analyzed in their raw form (cut / shredded leaves) or as an infusion that had been prepared with only one tea bag (containing 2-3g of tea) in 250 mL of distilled water in fine bone china cups.

As you will already have expected, the scientists did not just detect the previously mentioned "good minerals" (exact values see Table 1), and a host of other beneficial trace elements, i.e.

• boron 19–115µg/L, cobalt 0.4–3.56µg/L, 
• copper 26–106µg/L, chromium 0.2–14.6µg/L, 
• iron 19–62.5µg/L, manganese 534–6351µg/L, 
• molybdenum 0.03–0.131µg/L, 
• selenium <0.1–0.34µg/L, 
• vanadium <0.01–0.151µg/L, and zinc 44.6–187µg/L,

in their samples. Schwalfenberg et al. found highly significant and, more importantly, physiologically relevant amounts of toxic elements, as well:

Table 2: Established toxicant limits in supplements (µg/day).

If you look at the value in Table 3 and compare them to the limits in Table 2, there is one thing you should keep in mind: These limits have been set by average exposure, not based on toxicity tests - that sounds very comforting, right?

"Public health warnings or industry regulation indicated" -- It sounds pretty fearmongering and I would not have used it as a subheading right beneath the introduction, if the statement "Public health warnings or industry regulation might be indicated to protect consumer safety." (Schwalfenberg. 2013) was no literal citation from the conclusion of the paper I have here right in front of me.

Table 3: Levels of mercury (Hg), lead (Pb), aluminum (Al), arsenic (As) and cadmium (Cd) in tea infusions after 3-4 or 15-17 min of brewing; all values in µg/L (Schwalfenberg. 2013)

A brief glimpse at the data in Table 3 does moreover confirm there are plenty of toxins in the average Canadian super market tea, but it does not tell you how problematic the contamination actually is. To understand that you'd have to cimpare those values to the established toxicant limits Table 2, which do - and this is and will always be ridiculous -  obviously depend on where you live *sarcastic laughter*... but enough of the unproductive sarcasm, let's see what we've got:

"All teas contained significant amounts of aluminum. Tea  leaves contained from 568 to 3287 ng/g of tea. All brewed teas steeped for 3 or 15 minutes contained detectable levels of aluminum. The range was 1131µgm/L to 8324µgm/L steeping for 3 minute and 1413µgm/L to 11449µgm/L steeping for 15 minutes. Only 2 teas had levels above acceptable limits at 3 minutes of brewing but 6 of the teas had levels greater than the upper acceptable daily limit of 7000µgm/L. Clearly letting tea steep for longer than 3 minutes is not advisable. Two of the organic green teas had levels above 10,000µgm/L brewed for 15 minutes."

In view of the fact that tea is by far not the only aluminum source you are expose to, the high levels of this toxic metal that easily accumulates in the body should be reason enough not to brew your tea - especially not organic tea - for more than 3 minutes.

Organic tea is a worse offender than regular

If you take a look at the amount of lead in the various tea samples it becomes even more obvious that "organic" tea is not necessarily better for your organs, as well. This is particularly true for the best-sellers green and black tea, both of which contain significantly more lead in the "organic" vs. "regular" variety.

Table 4: Toxicant levels according to origin; Pb: lead, Cd: cadmium, Al: aluminum, As: arsenic (Schwalfenberg. 2013)

Probably the main factor that influences the toxicant levels of teas is the place of origin, thoug. As you can see in the overview in Table 4, the highest amount of arsenic, was detected in Chinese oolong teas (organic or regular). The total arsenic levels in all teas, which ranged from 0.06µgm to 1.12µgm/L for tea that had been steeped for 3 minutes to 0.08 to 1.27µgm/L for tea that had been steeped for 15 minutes was highest in white tea - obviously also from China. And last but not least, ...

"...[a]ll tea leaves had detectable levels of cadmium. 21 teas had detectable levels after 15 minutes brewing while only 18  teas had detectable levels after 3 minutes brewing suggesting that there is further leaching of this toxicant into the water over time. [As the overview in Table 4 already suggests] the highest level was 0.067µgm/L found in standard oolong tea from China." (Schwalfenberg. 2013)

Not listed in the tables are the levels of tin, barium, antimony and thallium, which were detected in all tea samples, but at levels of which the authors state that they don't have to be "considered to be of concern" (Schwalfenberg. 2013).

Should you stop drinking tea? You know that I don't like to tell people what to do. Unless, obviously I am 100% sure that I am convinced that there is a serious health risk involved.

In the case of green, black or white tea, the evidence that this is the case is yet insufficient. Personally, I will still make sure to check the geographic origin of the tea leaves (not where it was processed and packaged!) and avoid all products with the bad 5-letter word C-H-I-N-A on the label.

Bottom line: "Not of concern" is not exactly what I would say about the overall results of the study at hand. I mean, in the end, the high levels of toxicants in some of the commercially available tea preparations - specifically those from China - could actually explain why the real-world results with commercially available teas and tea supplements often fall short of the rodent studies, which are often conducted with highly purified green tea products from companies like Sigma Aldrich.

Ah, ... one last thing to keep in mind is that 18 out of 30 tested commercial tea preparations contained mercury in amounts that were as high as 20 ng/g, but did not make it from the leave to the tea. With your digestive tract being a much more efficient nutrient and (unfortunately) toxicant extractor than hot water, tea supplements could pose an even greater risk of heavy metal exposure than tea.

References:

• Álvarez-Ayuso, E., Giménez, A., & Ballesteros, J. C. (2011). Fluoride accumulation by plants grown in acid soils amended with flue gas desulphurisation gypsum. Journal of hazardous materials, 192(3), 1659-1666.
• Hayacibara, M. F., Queiroz, C. S., Tabchoury, C. P. M., & Cury, J. A. (2004). Fluoride and aluminum in teas and tea-based beverages. Revista de Saúde Pública, 38(1), 100-105.
• Lung, S. C. C., Cheng, H. W., & Fu, C. B. (2007). Potential exposure and risk of fluoride intakes from tea drinks produced in Taiwan. Journal of Exposure Science and Environmental Epidemiology, 18(2), 158-166.
• Steinmann, J., Buer, J., Pietschmann, T., & Steinmann, E. (2013). Anti‐infective properties of epigallocatechin‐3‐gallate (EGCG), a component of green tea. British journal of pharmacology, 168(5), 1059-1073.
• Tan, Z., & Xiao, G. (2012). Leaching characteristics of fly ash from Chinese medical waste incineration. Waste Management & Research, 30(3), 285-294.
• Schwalfenberg, G., Genuis, S. J., & Rodushkin, I. (2013). The Benefits and Risks of Consuming Brewed Tea: Beware of Toxic Element Contamination. Journal of toxicology, 2013.
• Wang, X. P., Ma, Y. J., & Xu, Y. C. (2008). [Studies on contents of arsenic, selenium, mercury and bismuth in tea samples collected from different regions by atomic fluorescence spectrometry]. Guang pu xue yu guang pu fen xi= Guang pu, 28(7), 1653-1657.

Organic vs. Conventional: The Overlooked Low Cadmium Advantage. Almost 50% Lower Cd Levels and Half-Lifes of 10-30 Years May Be Another Reason to Buy Organic

Eating organic is not so much about what you get extra (vitamins etc.), but rather about paying more for getting less. Less pesticides and, as recent studies show, significantly less cadmium.

In view of the hype around organic produce, it would appear as if this was a bogus question, but previous studies were not able to confirm any of the huge claims you will read all over the internet. The only established benefit so far - and that's certainly not one you should underestimate - appears to be a relative lack of pesticides.

Only recently scientists have compared a broad variety of organic and conventially grown crops and found that organically grown crops do tend to have a notably lower cadmium content, as well. According to  conventionally grown crops – on average, about 48 % lower (this estimate takes into account 87 previously reported comparisons).

Learn more about the effects of your diet on your health at the SuppVersity

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Taste Matters - Role of the Taste Receptors

Dairy Protein Satiety Shoot-Out: Casein vs. Whey

How Much Carbs Before Fat is Unhealthy?

5 Tips to Improve & Maintain Insulin Sensitivity

Carbohydrate Shortage in Paleo Land

In view of the fact that the heavy metal cadmium (Cd) is emerging as a major cause of vascular disorders, various common cancers, kidney disease, osteoporosis and other health disorders, even in populations that do not have occupational exposure to this toxin(2–4), this is significant news.

With the exception of smokers, who are constantly exposed to significant amounts of cadmium, green vegetables, root vegetables, tubers, grains, organ meats and shellfish are the major sources of this toxin. Any reduction of the Cd levels in these foods may thus have significant beneficial health implications, since once Cd gets into your body, it cannot be excreted again.

Scientists estimate the half-life of cadmium in the human body to be 10–30 years (Suwazono. 2009)! Thus every nanogram you don't consume counts!

While cadmium can induce oxidative stress throughout the body, and interference with some of the physiological roles of Zn (as in DNA repair), the evidence that dietary (not smoke) exposure to cadmium has significant health effects is yet scarce.

There is something you can do to reduce cadmium absorption: Iron deficiency increases the efficiency of dietary Cd absorption and will put you at increased risk of toxicity. In addition to a correction of any existing iron deficiency, Zn and Mg may lessen the absorption of dietary Cd to some degree (Gallagher. 2011; McCarty. 2012)

This is partly due to the fact, though, that our ability to measure the chronic effects of very low doses of a certain toxic substance are very limited. In a recent review, McCarthy et al. (2014) list the following hitherto published studies:

• 

  Table 1: Whether there are more or less antioxidants in organic produce depends on the antioxidant you're looking at (Barański. 2014)

  Japanese researchers have long speculated about an involvement of cadmium exposure in the development of breast cancer and researchers from all around the world have speculated based on elevated urinary Cd concentrations that it may be responsible for 27-68% of the breast cancer cases (McElroy. 2006; Gallagher. 2010; Nagata. 2013).
• Recent multivariate-adjusted analyses of the National Health and Nutrition Survey cohort have concluded that Cd exposure may be responsible for 28 % of the myocardial infarction cases and 17 % of the total CVD and cerebrovascular disease cases (Everett. 2008; Agarwal. 2011). And data from the prospective Strong Heart Study (focusing on Native Americans) suggest that Cd exposure may account for 16, 23 and 28 % of the coronary disease, stroke and heart failure cases, respectively (Tellez-Plaza. 2013).

In spite of the fact that the epdidemiological evidence is not exactly abundant and disregarding the null results of case-control studies attempting to correlate dietary Cd intake with disease risk McCarthy et al. conclude that "if one focuses on urinary Cd concentrations when surveying Cd epidemiology, the hazard of Cd stands out crystal-clear" (McCarthy. 2014).

Organic or conventional? Learn more in my previous article about he different pesticide levels.

Bottom line: In view of the fact that vitamin content of organically grown produce is not necessarily higher (depends on the crop) and considering the fact that Baranski et al. found that organically grown crops do not have a lower content of lead or arsenic, two other mineral contaminants linked to health risks, when compared with conventionally grown crops, the lower cadmium along with the lower pesticide content I wrote about previously, remain the major scientifically verified advantages of organically grown produce.

That's obviously less than the internet gossip would suggest, but still enough to have anyone who is seriously concerned about his health can afford them choose organic over conventional produce | Comment on Facebook!

References:

• Agarwal, Shikhar, et al. "Heavy metals and cardiovascular disease: results from the National Health and Nutrition Examination Survey (NHANES) 1999-2006." Angiology 62.5 (2011): 422-429.
• Barański, Marcin, et al. "Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses." British Journal of Nutrition 112.05 (2014): 794-811.
• Everett, Charles J., and Ivar L. Frithsen. "Association of urinary cadmium and myocardial infarction." Environmental research 106.2 (2008): 284-286.
• Gallagher, Carolyn M., John J. Chen, and John S. Kovach. "Environmental cadmium and breast cancer risk." Aging (Albany NY) 2.11 (2010): 804. 
• Gallagher, Carolyn M., John J. Chen, and John S. Kovach. "The relationship between body iron stores and blood and urine cadmium concentrations in US never-smoking, non-pregnant women aged 20–49 years." Environmental research 111.5 (2011): 702-707.
• McCarty, Mark F. "Zinc and multi-mineral supplementation should mitigate the pathogenic impact of cadmium exposure." Medical hypotheses 79.5 (2012): 642-648.
• McCarty, Mark F., and James J. DiNicolantonio. "Are organically grown foods safer and more healthful than conventionally grown foods?." British Journal of Nutrition 112.10 (2014): 1589-1591.
• McElroy, Jane A., et al. "Cadmium exposure and breast cancer risk." Journal of the National Cancer Institute 98.12 (2006): 869-873. 
• Nagata, Chisato, et al. "Cadmium exposure and the risk of breast cancer in Japanese women." Breast cancer research and treatment 138.1 (2013): 235-239.
• Suwazono, Yasushi, et al. "Biological half-life of cadmium in the urine of inhabitants after cessation of cadmium exposure." Biomarkers 14.2 (2009): 77-81.
• Tellez-Plaza, Maria, et al. "Cadmium exposure and incident cardiovascular disease." Epidemiology 24.3 (2013): 421-429.

Alarmingly High Levels of Lead in Calcium Supplements: Pb Content per Serving Up to 18x Over "Acceptable Levels".

Image 1: You better pick the right source of calcium: healthy milk / dairy vs. lead poisoned pills from your local pharmacy or supermarket - you still have the choice.

This, I can assure you, is a "SuppVersity News", i.e. something you will not read on the major news portals, simply because there is too much money at stake in the 3billion $ market for calcium supplements (figure according to January 2008 edition of "Heartwire") - money a huge part of which is spent by Novartis & Co to advertise their products to consumers from all age groups, regardless of the individuals' dietary calcium intake; and that despite accumulating evidence for an association of supplemental calcium intake and heart disease (for one of the latest reviews cf. Bolland. 2011)! A very recent study published in the Journal of Biological Trace Element Research (Rehman. 2011) does yet cast another, even darker shadow onto the "healthy" white chalk tabs...

What? "Pb" is not the symbol for Calcium in the Periodic Table?

Lead, that stuff nuclear physicists value, because it effectively absorbs radioactive radiation, is one of the most toxic "heavy metals" we are exposed to. And this is by no way a recent discovery. Even in ancient times, people knew about the toxic effect vessels made of this metal had on the water they contained. Back in 1990 E.K. Silberberg summarized the contemporary knowledge about the dangers of environmental lead exposure in a paper for the Environmental Defense Fund as follows (Silberberg. 1990):

[...] epidemiological studies have suggested that central nervous system (CNS) effects in children are observed at the lowest increments of lead exposure [...] Similarly, clinical studies indicate that early exposure to lead produces functionally irreversible damage to the CNS; experimental research demonstrates that this irreversibility may involve failure to remove lead from brain, permanent effects on synaptogenesis; and chelant-induced redistribution of lead from the periphery to the CNS. [...] New data on release of bone stores of lead during physiological conditions of demineralization indicate that mobilization of bone lead adds to in utero exposure of the fetus. Furthermore, postmenopausal demineralization of bone can increase blood lead levels in women by 25%; this raises concern about the potential effects of lead in an aging population and the difficulties in comprehensive exposure assessment.

As you may have guessed, time has not affected the dangers or the irreversibility of lead toxicity, so that you would assume that the results of an investigation into the lead content of 27 "commonly used" commercially available calcium supplements should be alarming enough to receive at least some public recognition. After all, it would suffice to read the abstract to be alarmed by the fact that of the calcium supplements Sohaila Rehman and her colleagues from the Pakistan Institute of Nuclear Science Technology analyzed only one out of ten "met the criteria of acceptable Pb levels (1.5µg/daily dose) in supplements / consumer products set by the United States" (Rehman. 2011).

Figure 1: Lead levels in µg in daily dose of respective calcium supplement; solid red line = acceptable Pb level for calcium supplements, dashed red line = tolerable total daily Pb intake for children <7y, dotted red line = tolerable daily Pb intake for women in childbearing age (data adapted from Rehman. 2011).

"One out of ten", well that does not sound so bad, does it? I guess you will change your mind, when you take a closer look at figure 1 - the red line at the bottom of the graph is the "acceptable Pb level" and as you can see it is met by exactly 1 out of 13 calcium chelate products (CAC 1000 by Novartis), and none of the 3 calcium chelates the researchers tested for their lead content.

Figure 2: Lead levels in µg in daily dose of respective calcium supplement; solid red line = acceptable Pb level for calcium supplements, dashed red line = tolerable total daily Pb intake for children <7y (data adapted from Rehman. 2011).

And while the lead levels of the calcium + vitamin C and calcium + vitamin D levels in figure 2 look somewhat better, there are still several outliers with Cal-C Plus from Himont Pharma, for example, providing more than 2x the tolerable daily lead intake for a child under the age 7 y (and remember these are only the official FDA figures - and you know what that means ;-) on a per serving base.

Note: The results of the study at hand may well explain a) the different outcomes of (controlled) trials and epidemiological studies on the effects of calcium supplements on cardiovascular health and b) the beneficial effects of milk and dairy intake on heart health (Soedamah-Mutuh. 2011). After all, a very recent study that was published in the Journal of Neurotoxicology and Teratology in October 2011, shows that there is a "potential for autonomic dysregulation" that manifests in "significantly greater vascular resistance and reduced stroke volume and cardiac output" in 9-11 year old children even "at levels of Pb typical for many US children" (the exact levels were 1.01µg/dL, cf. Gump. 2011).

And as if all that was not enough, the US Food and Drug Administration (FDA) and the glorious Center for Disease Control and Prevention (CDC) would have been aware of the potential of serious chronic lead intoxication from calcium supplements, if they spent more time reading scientific journals than counting the cashflow from the BigPharma companies that finance their bureaucracy. After all, Bourgoin et al. conducted a very similar study back in the 1990s, the results of which the scientists summarize in their abstract as follows (Bourgoin. 1993):

Daily lead ingestion rates revealed that about 25% of the products exceeded the US Food and Drug Administration's "provisional" total tolerable daily intake of lead for children aged 6 years and under.

In the Rehmann study it were 16 out of 27 tested calcium supplements (59%) which exceeded this limit. So  maybe the "feds" just did not act, because 1 out of 4 is not bad enough? Well, if you look at the individual results in figure 3 (usually I redo graphs, but in this case the original looks just too damn impressive), it is immediately obvious that the averages the scientist report in their abstract, do not reflect the actual potential of lead toxicity from the 70 supplemental sources Bourgoin et al. tested.

Figure 3: Results of a 1993 large-scale analysis of the lead content of 70! commercially available calcium supplements and milk (my emphasis), the safe exception (from Bourgoin. 1993)

Obviously, some of the bone based and a whole host of the "natural sources" ("natural source of calcium carbonate" according to label claim; note that coral calcium would fall into this category, as well!) are about as toxic as the worst offenders in the Rehman study. What I find do yet find particularly interesting, is that the lead content in one serving of commercial milk, which would provide the same amount of (even more bioavailable) calcium as the supplements in the study did, would provide no more than 0.71µg/day and is thusly the one and only "natural source" of dietary calcium that does not set you up for lead toxicity!

"Pah, lead!? What doesn't  kill you just makes you stronger"

Image 2: So, calcium supplement with lead are a safe source of dietary calcium, but raw milk is not? (img CounterThink)

In view of the "longstanding" history of ignorance on behalf of the governmental agencies, it sounds almost sarcastic, when Bourgoin et al. conclude their article by citing the Center for Disease Control's (CDC) statement on lead poisoning, which according to these reputable protectors of the health of the American society *cough* is "one of the most common and preventable pediatric health problems today". Notwithstanding this early insight (this is from a 1991 document from the CDC) the officials obviously have neither taken Bourgoin et al.'s advice to control calcium supplements "more rigidly" in order to "prevent unnecessary exposure in all segments of the population, particularly young children" (Bourgoin. 1993), nor have they followed the recommendation of a more recent study by Kim et al., which  estimates the mean lead intake from calcium supplements to about 5µg/day and recommends that "measures to prevent potentials of Pb toxicity from overtaking some Ca supplements should be considered" (Kim. 2010).

And while the CDC and the FDA could incidentally have missed those papers. They should actually be aware of Proposition 65, which is the common name for California's Safe Drinking Water and Toxic Enforcement Act of 1986 (Dietary Supplement Standard 173, Metal Contaminant Acceptance Levels. NSF International. August 19, 2003). In this paper, of which W.W. Kilgore writes in retrospective that (Kilgore. 1990)

[i]t creates a list of chemicals (including a number of agricultural chemicals) known to cause cancer or reproductive toxicity; [i]t limits discharges of listed chemicals to drinking water sources; [i]t requires prior warning before exposure to listed chemicals by anyone in the course of doing business; [i]t creates a list of chemicals requiring testing for carcinogenicity or reproductive toxicity; and [i]t requires the Governor to consult with qualified experts (a 12-member "Scientific Advisory Panel" was appointed) as necessary to carry out his duties.

the proposed Acceptable Intake Level (AIL) for inorganic lead (as extrapolated from animal studies) is 0.5µg/day and thusly 1/3 of the current Californian standards and 1/50 of the FDA allowance of 25µg/day! But hey, who cares? As long as the American citizens are protected from the dangers of raw milk, everything is all right, isn't it?