True or False: Mycotoxins in Coffee Are a Serious Threat to Our Health and the Only Way to Avoid Them is Abstinence

As we are about to see coffee is by far not the worst aflotoxin offender in the human diet. Still, that does not mean that the coffee related exposure to this form of mold that can befall all sorts of grains, nuts and seeds is harmless.

You will probably remember that I casually touched on the possibility of being exposed to aflotoxins and more importantly ochratoxins as a result of the consumption of mold-infected coffee in previous coffee articles. When the issue of the « coffee ➲ aflotoxin / ochratoxin exposure ➲ serious health » triage resurfaced in a brief facebook conversation, recently, I realized that I was not 100% sure if these mycotoxins that are produced by Aspergillus flavus, Aspergillus ochraceus, Aspergillus niger, and Aspergillus carbonarius do or don't pose a serious health risk.

Well, you know how much I hate unanswered questions, so I kept digging until I'd found what I consider to be a half-way satisfying answer to this life-or-death question ;-)

You can learn more about coffee at the SuppVersity

Remember: With Coffee More Won't Help More

Coffee - The Good, Bad & Interesting

Three Cups of Coffee Keep Insulin At Bay

Caffeine's Effect on Testosterone, Estrogen & SHBG

Coffee + Cacao for Breast Cancer Prevention

"Decaf" Won't Help With Weight, ... Ahh, Fat Loss

"The amount of aflotoxin in the average cup of coffee is a serious threat to our health!"

In 90% of the cases the above statement is FALSE! Despite the fact that it is difficult to tell how much mycotoxins you've been flushing down with your morning coffee today, the exact amount of the more common aflotoxins and their similarly kidney-toxic, pro-carcinogenic and coffee-loving cousins, the ochratoxin, in the average cup of (roasted) coffee is probably way too low to be worried about.

Figure 1: Mycotoxin exposure from coffee; calculated based on data from Europe (Vd Stegen. 1997)

Based on the studies I have reviewed for this article, it appears almost certain to say that the relatively low amount of coffee beans per cup (4-8g) reduces your average mycotoxin exposure from 1-4 cups of coffee per day to levels that are almost certainly within one of the various (multi-)national reference ranges (Van Egmond. 2007):

• Europe: 5µg/kg
• Africa: 10µg/kg

• North America: 20µg/kg

• Asia: 15µg/kg
• Latin America: 20µg/kg

Using a selection of commercially available regular and soluble coffee brands, van der Stegen et al. have actually calculated the average daily mycotoxin intake of Europeans with an average coffee consumption of 1-4  to be in the nanogram range - 19ng and 10ng, specifically, for regular and instant coffee drinkers, respectively.

Please remember: We don't know if / what happens or doesn't happen if you stay within or break the arbitrary intake limits. If you take a look at the available evidence from rodent studies, the results Epstein et al. presented in their 1969 paper (see Table 1) later in this article, would suggest that a sensible intake limit would have to be below the 1µg range if we assume a similar toxicity for the average mycotoxin mixture as for the aflotoxin B Epstein et al. used. This assumption is obviously not realistic, but it should remind you of the arbitrariness of the "intake limits".

Just to make sure, we understand each other, here: That's 1000x less than you'd get from only 20g of some of the Brazilian peanuts Freitas and Brigido analyzed in a 1998 study for their mean and maximal mycotoxin content. With 1099µg/kg the worst offenders in this study would easily have you breach the already lax American (North & Latin America) max. tolerable intake limit of 20µg/kg per day - and that despite the fact that this limit is more than 1000x higher than the amount of mycotoxins you'll have in your average cup of coffee.

Green vs. roasted coffee: Do we have to chose between anti-oxidants and mycotoxins?

It goes without saying that the mere fact that the dangers of being exposed to high amounts of mycotoxins from adequately processed and stored coffee appears negligible, does not warrant ignoring the problem completely. The effects of processing and storage are and will thus always be an important issue.

Given the fact that humid and cool (but not cold) is what mold needs to thrive, you will probably already have suspected that the hot and arid environment of a coffee roastery is not exactly the favorite growth environment for the Aspergillus family.

Figure 2: Ochratoxin content (µg/kg) in green, roasted & soluble coffee, left; total antioxidant activity in TROLOX essay of green (=unroasted), lightly, medium and dark roast coffee (Blanc. 1998; del Castillo. 2002)

A lower mycotoxin content is yet not the only beneficial effect of roasting. Contrary to what 99% of the people will tell you, when you ask them, the roasting process increases not decreases the total antioxidant capacity of coffee (TAC).

What does the latest review say about regular coffee consumption and cancer? "The epidemiological evidence consis-tently indicates that coffee protects against liver cancer, and also point toward protective effects for risk of colorectal cancers (with relative risks of 0.50 (95% CI: 0.42–0.59) and 0.83 (95% CI: 0.75–0.92), respectively, in the most recent meta-analyses)" (Bøhn. 2013). The evidence for protective effects against breast and prostate cancer on the other hand is inconclusive - irrespective of the established chemo-preventive effects of coffee phytochemicals Bøhn et al. list in their soon to be published paper in Molecular Nutrition & Food Research early in 2014.

Due to the formation of a whole host of new antioxidant molecules during the roasting process, light or mildly roasted coffee beans have a higher total antioxidant capacity than green ones - irrespective of the reduced chlorogenic acid content, for which the green beans are currently (over-)hyped. If you look at the data in Figure 2 you will see that even the heavily roasted, tar-black coffee beans still have a minimally higher anti-oxidant activity than the "natural" green coffee beans (del Castillo. 2002) - an observation that has been made both in the Petri dish, as well as ex vivo rodent studies (Daglia. 2002).

You've been drinking tons green coffee, lately?

Don't worry! Your past green coffee consumption probably isn't a real problem either. It does after all look as if those beans were yet another example for the infamous "nature kows best" principle. I mean, can it really be "coincidence" that the beans come with "anti-mycotoxin agents" in form of cafestol and kahweol. These coffee-specific diterpenes have been shown to ameliorate the aflotoxin B induced genotoxicity (Cavin. 1998) and the subsequent pro-carcinogenic effects (Cavin. 2001) and can be expected to exert protective effects against ochratoxin toxicity, as well.

In view of the fact that similar evidence exists for chlorogenic acids (CGA), dodecyl chlorogenates (DCGA) and a high(er) coffee consumption, in general (Suárez‐Quiroz. 2013; Ferk. 2013), it is actually not surprising that studies like Shank et al. (1972)  or Bulatoa-Jaym et al. (1982) found links between aflotoxin contaminated corn, grains, potato, peanuts & co., but could not identify an increased risk in liver cancer for coffee aficionados. Consequently, it's (imho) relatively unlikely that your health has already taken a beating - irrespective of the amount of the number of cups of green coffee you've been consuming over the past weeks.

Coffee is not the worst mycotoxin offender in the human diet: In a case-control dietary study of primary liver cancer in humans Bulatoa-Jaym et al. found that 51.2% of their subjects daily aflotoxin exposure came from cassava, 20.3% from corn, 6.8% frompeanuts and 5.8% from sweet potato (Bulatao-Jaim. 1982). On the other hand, many scientists argue that the ochratoxin content of coffee is the real danger, anyway (Bayman. 2006)

I would still like to remind you that even the sum of the previous remarks must not be misunderstood as an incentive to willy nilly forget all previously harbored concerns about "moldy coffee beans"... and I say this in spite of the existing epidemiological evidence that a high coffee consumption decreases the risk of developing and dying from liver cancer (Kurozawa. 2005; El–Serag. 2007). The liver is after all not the only organ that may be affected by the pro-carcinogenic toxins. The kidneys are at least as susceptible to the toxic assault from the mycotoxin filtrate that passes through them.

The liver is not the only organ that's taking a beating

It may thus be hypothetical, but not impossible that a 2x / 2.6x increased risk to develop renal cell carcinoma Mimi et al. report in a 1986 paper on the associations between coffee consumption and kidney cancer may at least be partially related to the higher mycotoxin exposure in those 61 study participants who consumed 1-4 cups of coffee per day (Mimi. 1986).

That mycotoxins can promote the development of kindey cancer had been demonstrated 17 years before the publication of Mimi's paper by Epstein, Bartus & Farber (1969) whose Wistar rats developed renal epithelial neoplasms after being exposed to food-borne aflatoxin B1.

Table 1: Incidence of renal epithelial and malignant hepatic tumors in male Wistar rats ingesting aflatoxin B1 for 147 days; the indces a, b, c provide irrelevant (in this context) extra information (Epstein. 1969)

In that, it's quite remarkable that even the lowest aflotoxin dosage the researchers used in their study (0.25µg/kg chow; HED  ~1.2ng/kg body weight, ; see Table 1) lead to significant rates of cancerous growth in both kidney (28%, if we count both developing and full-blown renal neoplasms) and liver  within the 21 week study period.

There is just one no-go: Storing unroasted beans for years in your humid basement

In view of the large regional difference in aflotoxin infection rates, the different susceptibility of the various coffee cultivars and the influences of weather, storage conditions, blending, processing, and all the other factors that increase or decrease the amount of mold and mycotoxins on coffee (see Figure 3), I would still be hesitant to exclude the possibility that stocking up on highly aflotoxin contaminated unroasted coffee you possibly even stock in a very humid basement of yours to consume the coffee over the course of months if not years could have negative effects on the health of your organs, in general, and the function of your kidney and liver, in particular.

Figure 3: Percent infection of coffee cherries and beans byAspergillusspecies potentially capable of producing ochratoxin A in four Brazilian coffee growing regions from the 1999 and 2000 harvests (Taniwaki. 2003)

I mean, look at the data in Figure 3. It's probably no coincidence that the otherwise virtually uninfected beans of coffee from the 1999 and 2000 harvests in the Cerrado Miniero exhibits a 4% infection rate after being stored intermediately before it is either roasted, shredded or both or simply forwarded "raw" to the mailbox of an "unroasted coffee enthusiast". Similar effects can be expected when the huge coffee manufacturers mix harvests from various regions. If only one is infected, all it takes to have Aspergillus flavus literally "all over the place" is enough time in one of the huge storage silos or the hold of one of the container ships that transport coffee from the "New" back into the "Old World".

Figure 4: The amino acid make up of coffee changes upon roasting (data from Cirilo. 2003).

Life kills, anyway! Let's be honest. In the end, living is a pretty deadly undertaking, anyway. Against that background the uncertainty with respect to the tolerable intake of mycotoxins should not bother you so much to ignore the existing evidence of the beneficial effects of regular coffee consumption (see "Coffee - The Good, the Bad & The Interesting" | read more).

One thing you may keep in mind, though, is that this evidence is based on data from average coffee drinkers, people who drink coffee that's made of roasted beans. Beans that are virtually mycotoxin-free (see Figure 2, left) and have a higher, not lower antioxidant capacity than green coffee beans.

What roasted beans lack, though, are chlorogenic acid and trace amounts of amino acids (see Figure 4), including serotonin. If you are looking for one of these molecules specifically, you are yet probably better of with a hopefully aflotoxin and mycotoxin free green coffee extract and a bottle of pills with the serotonin precursor 5-HTP, anyways.

References:

• Bayman, P., & Baker, J. L. (2006). Ochratoxins: a global perspective. Mycopathologia, 162(3), 215-223. 
• Blanc, M., Pittet, A., Muñoz-Box, R., & Viani, R. (1998). Behavior of ochratoxin A during green coffee roasting and soluble coffee manufacture. Journal of agricultural and food chemistry, 46(2), 673-675.
• Bøhn et al. (2013) Coffee and cancer risk, epidemiological evidence, and molecular mechanisms. Molecular Nutrition & Food Research [early view article]
• Bulatoa-Jaym J, et al. (1982). A Case-Control Dietary Study of Primary Liver Cancer Risk from Aflatoxin Exposure*. International journal of epidemiology, 11(2), 112-119.
• Cavin, C., Holzhäuser, D., Constable, A., Huggett, A. C., & Schilter, B. (1998). The coffee-specific diterpenes cafestol and kahweol protect against aflatoxin B1-induced genotoxicity through a dual mechanism. Carcinogenesis, 19(8), 1369-1375.
• Cavin, C., Mace, K., Offord, E. A., & Schilter, B. (2001). Protective effects of coffee diterpenes against aflatoxin B< sub> 1</sub>-induced genotoxicity: mechanisms in rat and human cells. Food and Chemical toxicology, 39(6), 549-556.
• del Castillo, M. D., Ames, J. M., & Gordon, M. H. (2002). Effect of roasting on the antioxidant activity of coffee brews. Journal of Agricultural and Food Chemistry, 50(13), 3698-3703. 
• Cirilo, M. P., Coelho, A. F. S., Araújo, C. M., Gonçalves, F. R., Nogueira, F. D., & Glória, M. B. A. (2003). Profile and levels of bioactive amines in green and roasted coffee. Food Chemistry, 82(3), 397-402.
• Daglia, M., Papetti, A., Gregotti, C., Bertè, F., & Gazzani, G. (2000). In vitro antioxidant and ex vivo protective activities of green and roasted coffee. Journal of Agricultural and Food Chemistry, 48(5), 1449-1454.
• Epstein, S. M., Bartus, B., & Farber, E. (1969). Renal epithelial neoplasms induced in male Wistar rats by oral aflatoxin B1. Cancer Research, 29(5), 1045-1050.
• El–Serag, H. B., & Rudolph, K. L. (2007). Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 132(7), 2557-2576. 
• Ferk, F., Huber, W. W., Grasl‐Kraupp, B., Speer, K., Buchmann, S., Bohacek, R., ... & Knasmüller, S. (2013). Protective effects of coffee against induction of DNA damage and pre‐neoplastic foci by aflatoxin B1. Molecular nutrition & food research. 
• Freitas, V. P., & Brigido, B. M. (1998). Occurrence of aflatoxins B1, B2, G1, and G2 in peanuts and their products marketed in the region of Campinas, Brazil in 1995 and 1996. Food Additives & Contaminants, 15(7), 807-811.
• Kurozawa, Y., Ogimoto, I., Shibata, A., Nose, T., Yoshimura, T., Suzuki, H., ... & Tamakoshi, A. (2005). Coffee and risk of death from hepatocellular carcinoma in a large cohort study in Japan. British journal of cancer, 93(5), 607-610. 
• Mimi, C. Y., Mack, T. M., Hanisch, R., Cicioni, C., & Henderson, B. E. (1986). Cigarette smoking, obesity, diuretic use, and coffee consumption as risk factors for renal cell carcinoma. Journal of the National Cancer Institute, 77(2), 351-356.
• Shank, R. C., Wogan, G. N., & Gibson, J. B. (1972). Dietary aflatoxins and human liver cancer. I. Toxigenic moulds in foods and foodstuffs of tropical South-East Asia. Food and Cosmetics Toxicology, 10(1), 51-60.
• Taniwaki, M. H., Pitt, J. I., Teixeira, A. A., & Iamanaka, B. T. (2003). The source of ochratoxin A in Brazilian coffee and its formation in relation to processing methods. International Journal of Food Microbiology, 82(2), 173-179. 
• Van Egmond, H. P., Schothorst, R. C., & Jonker, M. A. (2007). Regulations relating to mycotoxins in food. Analytical and bioanalytical chemistry, 389(1), 147-157. 
• Vd Stegen, G., Jörissen, U., Pittet, A., Saccon, M., Steiner, W., Vincenzi, M., ... & Schlatter, C. (1997). Screening of European coffee final products for occurrence of ochratoxin A (OTA). Food Additives & Contaminants, 14(3), 211-216. 
• Yamato, T., Yamasaki, S., Misumi, Y., Kino, M., Obata, T., & Aomine, M. (2002). Modulation of the stress response by coffee: an in vivo microdialysis study of hippocampal serotonin and dopamine levels in rat. Neuroscience letters, 332(2), 87-90.

100-200ml Red Wine Per Day Improve HDL and the LDL/HDL Ratio With & Without Mediterranean Diet & Exercise

Good for him, good for her, good for everyone? Is it really possible that red wine can help even those who don't want to the necessary lifestyle changes?

You all know about the limitations of epidemiological studies and the fallacy of the over-generalization of associations between health parameters and red wine consumption in the mainstream media. For me this *bs* is so annoying that I usually don't even take a look at "red wine studies". Luckily, a recent paper by Dirk W. Dorste and his colleagues did still catch my attention: It's about to be published in the December issue of Nutrition Journal and is not based on epidemiological data.

The Luxembourgian scientists gathered their data in the course of a randomized unblinded 2-year trial that involved 108 patients with carotid atherosclerosis and >30% reduced blood flow (65% of the patients were on statin therapy).

122 patients, 4 intervention groups, red wine and/or lifestyle changes

While half of the patients did nothing to improve their health and fitness, the other half of the patients, the lifestyle change group, had to follow a modified Mediterranean diet and perform moderate physical exercise during 30 min/day for 20 weeks. In both of these groups half of the patients were randomized either to no alcohol or red wine groups (100ml/day for women, 200ml/day for men). The end results of this process was a 2 x 2 design that looked like this:

• Med. diet + exercise only
• Med. diet + exercise + red wine

• regular diet + laziness only
• regular diet + laziness + red wine

While the subjects in the groups in the left "regular diet + laziness" column did not receive any dietary advice and were not encouraged to work out, the participants in the "Med. diet + exercise groups" had five 30 min sessions with a registered dietitian "giving advice on healthy eating based on a modified Mediterranean diet and physical exercise" - the cornerstones of this advice were:

• 

  Not into red wine? Learn about "The Ergogenic Effect of Nonalcoholic Beer Front- & Back Loading" | more

  eat 5 portions of fruit/vegetables per day, 
• consume a diet low in absolute fat, 
• prefer vegetable oil (olive or canola oil), 
• eat whole grain products, poultry, low fat dairy products, 
• consume a fat and a lean fish meal per week,
• reduce your consumption of red meat, 
• avoid pork and ready made-meals,
• stay away from sugar and excessive amounts of salt,
• drink 1.5-2 l plain water every day,
• eat the occasional 25g of dark (70%) chocolate,
• include tomatoes and walnuts in your diet,
• get at least 30 min of moderate daily physical activity

Yes, I know, not all of these points are exactly in line with what you (and even I) believe to be cornerstones of a healthy diet, but I do not write about this study, because it was an awesome example for highly beneficial lifestyle changes - quite the contrary: I picked it because the booze worked even without lifestyle changes:

Figure 1: Relative changes (in %) in total cholesterol, LDL, HDL, LDL/HDL and triglycerides after 4 and 20 weeks on one of the four "interventions" (Droste. 2013)

If you compare the red wine only and lifestyle only data from the end of week 20, it is not easy to tell the difference between the two - the greater improvements in HDL cholesterol, and higher reductions in LDL actually give the impression that simply guzzling red wine would be more effective than reinventing your diet and exercise habits

If we take a closer look at the data we do yet (luckily) have to acknowledge that the the subjects who did reinvent their lives were the only ones with lasting beneficial effects on total cholesterol, HDL, the LDL/HDL ratio and the total amount of triglycerides after 20 weeks - and that irrespective of the missing dietary and exercise / training control and despite the disputable dietary advice they received!

"Hard Liquor Increases Post Workout Testosterone by Almost 100% " | more

Bottom Line: This is not the experiment to confirm the hilarious mainstream media hype about the health benefits of red wine, but the results of this prospective study are still intriguing. They do after all support the hypothesis that the literal glass of wine can actually be a crutch that helps you to take a first baby step towards a healthier life. It does not hamper, but improve the beneficial effects of lifestyle interventions on CVD-relevant plasma markers and it's stand-alone effect on the HDL/LDL ratio is - I have to admit that - downright surprising.

Reference:

• Droste, Dirk W., et al. "A daily glass of red wine associated with lifestyle changes independently improves blood lipids in patients with carotid arteriosclerosis: results from a randomized controlled trial." Nutrition journal 12.1 (2013): 147.

Gluten Free, But not Suitable For Celiacs: Milk, Chocolate, Corn, Instant Coffee and 20 Other Foods & Food Ingredients That Could Cross-React With Gluten Anti-Bodies

Unless you got the right, i.e. breast milk as a baby and have rendered your gut "gluten proof" - being breast fed, when you are first exposed (or being exposed later in life) has after all been suggested as a protective factor (Farrell. 2005)

This is not going to be a long post; and still, at least for some of you it is going to be an important post. A post that may have the potential to change your life for the better or for the worse depending on whether you actually suffer from gluten-intolerance or have simply been bamboozeled by the "gluten is the devil" messages that are plastered all over the Internet these days.

Actually, I would hope that you belong to neither of the groups and can thus simply ignore this post. For the unfortunate rest, I have prepared a mini-summary of the results of a recent study from the Immunosciences Lab in Los Angeles (Vojdani. 2013)

Milk and cornflakes - a killer combo

A couple of recent studies, as well as reports from patients all of which clearly suggested that "being gluten free" does not equal "being symptom free" had spiked the researchers interest. Was it possible that the persistent symptoms were brought about by cross-reactions between the anti-bodies that would usually attach to the gluten proteins to trigger an immune reaction and other molecules? Molecules from such innocent foods, as dairy, chocolate, and even coffee!?

Suggested read: "Leaky Gut & Gluten Belly: Bacterial Firebugs Translocate from Your Gut to Your Ever-Growing Visceral Fat Depots" | read more

"[W]hen histological response was assessed in celiac patients after 6 months of following a GFD [gluten free diet], complete normalization and reconstruction of villous architecture was observed only in 8% of individuals, while 65% of these patients were in remission and 27% did not respond to GFD and had no observable change in their clinical symptoms (Lanzini. 2009).

The lack of improvement in histopathology and clinical symptomatology in a subgroup of patients on a GFD may be associated with dietary non-ad-herence or cross-reactive epitopes triggering a state of heightened immunological reactivity in gluten-sensitive individuals (Hadjivassiliou. 1997)." (Vojdani. 2013)

The hypothesis certainly isn't totally odd. Kristjansson et al. were for example able to show that 50% of their celiac patients experienced a significant mucosal inflammatory response similar to that elicited by gluten, when they were exposed to cow’s milk protein. Of the 15 healthy controls in their study, however, not a single one showed the slightest signs of auto-immune related inflammatory processes (Kristjansson. 2007).

So is this "real" celiac disease?

It should be obvious though that the corresponding "cross reactive" agents do not induce celiac disease (which is per definition an auto-immune disease that's triggered by the reaction to gliadin). They are however well able to alter the intestinal barrier integrity - a symptom that is also one of the key feature of the early stages of celiac disease.

Figure 1: Reaction of affinity-purified α-gliadin 33-mer polyclonal antibodies to gliadin and different food antigens; data in large figure relative to control, data in small inset relative to a-gliadin (Vodjdan. 2013)

If full remission of celiac disease cannot be achieved even on gluten-free diet, the underlying reason may thus well be the presence of peptides and antigens that (cross-)react with the same anti-bodies the body of celiac patients produces against the α-gliadin 33-mer peptide aka gliadin. Scientists even speculate that the co-exposition to these agents could eventually lead to the establishment of "new" auto-immune diseases and food allergies and some argue that the ever-increasing spectrum of allergies is partly a result of untreated autoimmune reactions which are then "spreading" to other previously well-tolerated foods and food ingredients.

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Suggested read: "Beyond Celiac: Study Sheds New Light on Obesogenic Effects of Gluten - Are PPARs & Bacteria Both Involved?" | read more

The problem seems real, if you're really gluten intolerant: With milk, all sorts of dairy products (including whey), instant coffee (but not espresso; see small inset), avenin containing oat products (unfortunately, I cannot tell you how you can recognize the "unproblematic" oats at the super market, but if you google "avenin-free oats" you will see a couple of products and stories pop up; Comino. 2011) and corn having a significant potential for cross-reactivity, it appears almost reasonable that some people come back from their visit with a mostly self-proclaimed expert in all things celiac with an endless list of items they are not supposed to eat and a tiny 5-item list of foods they are supposed to live on for the rest of their lives.

What is not reasonable, however, is that this is the case for more and more people who are basically asymptomatic... well, aside from their "inability to lose weight" that is obviously not related to their "inability to exercise" and their "inability to stop watching TV and browsing the Internet for easy quick-fix solutions to obesity problems", but most obviously be brought about by gluten intolerance ;-(

References:

• Comino I, Real A, de Lorenzo L, Cornell H, López-Casado MÁ, Barro F, Lorite P, Torres MI, Cebolla A, Sousa C. Diversity in oat potential immunogenicity: basis for the selection of oat varieties with no toxicity in coeliac disease. Gut. 2011 Jul;60(7):915-22.
• Hadjivassiliou M, Chattopadhyay AK, Davies-Jones GA, Gibson A, Grünewald RA, Lobo AJ. Neuromuscular disorder as a presenting feature of coeliac disease. J Neurol Neurosurg Psychiatry. 1997 Dec;63(6):770-5.
• Kristjánsson G, Venge P, Hällgren R. Mucosal reactivity to cow's milk protein in coeliac disease. Clin Exp Immunol. 2007 Mar;147(3):449-55.
• Lanzini A, Lanzarotto F, Villanacci V, Mora A, Bertolazzi S, Turini D, Carella G, Malagoli A, Ferrante G, Cesana BM, Ricci C. Complete recovery of intestinal mucosa occurs very rarely in adult coeliac patients despite adherence to gluten-free diet. Aliment Pharmacol Ther. 2009 Jun 15;29(12):1299-308. 
• Vojdani A, Tarash I. Cross-reaction between gliadin and different food and tissue antigens. Food and Nutrition. 2013; 4:20-32.

Liver Enzymes the #1 Marker of Insulin Resistance!? Plus: What Does the Correlation Bettwen HbA1C & ALT, AST and GPT Tell Us About Diabesity?

Just like type II diabetes, NAFLD is a life-style disease.

While it may not be obvious, today's SuppVersity post is very closely related to Sunday's post about supplements to battle insulin resistance. The recent revelation that the liver enzymes alanine transaminase (ALT aka GPT), aspartate transaminase (AST aka SGOT) and gamma-glutamyl transpeptidase (GGT aka gamma-GT) and not free fatty acid levels are the most reliable predictors of insulin sensitivity in overweight and obese, non-diabetic adults does after all show clearly support the notion that we (scientists, doctors, patiens) should pay much more attention to the liver. It's the liver that controls blood glucose, lipids and even our hormone levels, not the adipose organ. Therefore it is in the liver, our metabolic organ #1, is where the dark diabesity magic happens.

Heal the liver, cure the insulin resistance

Just in: A recent Stanford study shows that the use of VEGF inhibitors that are usually prescribed as cancer drugs can help diabetics manage their blood glucose levels, by increasing the expression of a protein (HIF-2alpha) that's usually expressed in response to hypoxic cell death and will - as a side effect - increase the expression of insulin receptors and thus restore hepatic insulin sensitivity and the optimal function of all the regularory processes that depend on it (Conger. 2013).

Usually you will think of being overweight and undermuscled, of insulin resistant myocytes (muscle cells) and adipocytes (fat cells) and about eating too much simple sugars, whenever someone is talking about the etiology of insulin resistsance. NAFLD, i.e. non-alcoholic fatty liver disease, on the other hand, is still often thought of as one of the long-term side effects of T2DM.

A recent study from the Children's Nutrition Research Centre at the University of Queensland does however suggest that the connection between having a messed up liver and being insulin resistant does not just start much earlier, than previously thought, but is probably also directly involved in the progression from being slightly insulin resistant to being a real diabetic.

Certainly, central adiposity (=high amounts of visceral, inter-organ fat) is and will always be one of the key risk factors for the development of insulin resistance and its progression towards full blown type 2 diabetes. Whether this is mainly a function of the spatial proximity of the constantly inflamed visceral fat depot to the liver is still a matter of current research. What we do know already is however that the presence of NAFLD is an independent risk factor for cancer and heart disease (Guebre-Egziabher. 2013)

Once the liver has taken a beating, the downstream effects are profound

One thing that's for sure, though, is that the downstream effect that occur, whence the liver is beginning to take a hit are profound:

• endocrine imbalances resulting from errors in the cytochrome enzymatic cascade that's responsible (among other things) for the conversion and clearance of all sorts of hormones
• messed up cholesterol levels and lipid profile with increases in LDL and VLDL lipoproteins and decreases in HDL
• chronically elevated  glucose levels due to lowered glycogen storage capabilities and a lack of control of the gluconeogenic processes in the liver that are no longer shut off when insulin is present, 
• increased fatique that's mediated at least in parts by the accumulation and build-up of toxic metabolic byproducts and environmental toxins the liver cannot handle any longer

The list goes on and on and I bet you that all 40 overweight and obese (body mass index≥25.0kg/m²) subjects with elevated ALT and AST values in the study at hand were already suffering from these problems.

Figure 1: Correltion coefficients for blood glucose, blood insulin and HbA1C (Gray. 2013)

No wonder that the data in Figure 1 confirms that there is no other parameter - including BMI, adiponectin, blood lipids, i.e. LDL, HDL, etc., I-CAM or ghrelin (the latter are not shown in the figure) that come remotely close as far as their reliability as markers of insulin resistance and the corresponding elevations of the long-term glucose marker HbA1C are concerned.

This does also mean that the study at hand would refute the results of previous experiments which suggest that the mobilization of FFA in the circulation promotes insulin resistance, however

Please remember: AST, ALT & CK will be elevated after workouts so take a couple of days off before you get blood work done.

"this [particular] study found no direct correlations between FFA and markers of insulin sensitivity. Furthermore, there were no clear correlations between markers of insulin sensitivity (glucose, insulin, HbA1C, or HOMA scores) and physical activity or self-reported fatigue. Fatigue scores were correlated with C-reactive protein, suggesting that inflammation may play a role, although there was no significant correlation with ICAM-1"(Gray. 2013)

Overall the currently data from the Gray study does therefore clearly support the notion that there is a  direct "link between liver function, adiposity, and the development of IR [insulin resistance]" (Gray. 2013) that goes well beyond the common understanding of 'adiposity begets insulin resistance, insulin resistance triggers NAFLD'.

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Figure 2: Liver tissue in rodents fed a hypercaloric high sucrose diet with (B) and w/out (A) taurine.  Taurine inhibited the development of hepatic steatosis (Gentile. 2011)

Bottom line: While the results of the study at hand certainly shift the focus away from the fat cells and towards the liver, they do not change the fact that "insulin resistance and the subsequent development of T2DM remain primarily lifestyle disorders" (Gray. 2013). In other words, if you followed all the "non-quick fix" tips from part I of the "Restore & Keep Insulin Sensitivity" series, in the first place - you would not have to worry about insulin resistance or non-alcoholic fatty liver disease (NAFLD).

Still, with a new emphasis on the involvement of the liver, the way we approach insulin resistance with supplements may in fact change... Although, when you come to think about it two of the top-supplements from the first and second serving of insulin sensitizing supplements, you will realize that many of them (e.g. alpha lipoic acid, taurine, berberine, etc.) are also known "liver protectors" (Gentile. 2011; Valdecantos. 2012).

Similar data on both improvements in liver health and insulin sensitivity is available for NAC (Haber. 2003) and milk thistle (Maghrani. 2004), as well. It is thus not too far off to assume that whatever you do to protect your liver is also going to have beneficial effects on your glucose metabolism; and what's even better it will improve your blood lipids, make your that your endocrine system works optimally, protect you against the constant assault of environmental toxins and reduce your chance of being carried off by diabetes, cancer and heart disease... still not convinced? Well, then think about something my good friend Carl Lanore likes to say "liver has the words 'to live' or 'life'" in it ;-)

References:

• Gentile CL, Nivala AM, Gonzales JC, Pfaffenbach KT, Wang D, Wei Y, Jiang H, Orlicky DJ, Petersen DR, Pagliassotti MJ, Maclean KN. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease. Am J Physiol Regul Integr Comp Physiol. 2011 Dec;301(6):R1710-22.
• Gray B, et al., Liver enzymes but not free fatty acid levels predict markers of insulin sensitivity in overweight and obese, nondiabetic adults, Nutr Res. 2013 [published ahead of print]
• Guebre-Egziabher F, Alix PM, Koppe L, Pelletier CC, Kalbacher E, Fouque D, Soulage CO. Ectopic lipid accumulation: A potential cause for metabolic disturbances and a contributor to the alteration of kidney function. Biochimie. 2013 Jul 27.
• Haber CA, Lam TK, Yu Z, Gupta N, Goh T, Bogdanovic E, Giacca A, Fantus IG. N-acetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in vivo: possible role of oxidative stress. Am J Physiol Endocrinol Metab. 2003 Oct;285(4):E744-53. Epub 2003 Jun 10.
• Maghrani M, Zeggwagh NA, Lemhadri A, El Amraoui M, Michel JB, Eddouks M. Study of the hypoglycaemic activity of Fraxinus excelsior and Silybum marianum in an animal model of type 1 diabetes mellitus. J Ethnopharmacol. 2004 Apr;91(2-3):309-16.
• Conger K. Approved cancer drug potentially could help treat diabetes, researchers find. <http://med.stanford.edu/ism/2013/september/diabetes.html> retrieved September 16, 2013.
• Valdecantos MP, Pérez-Matute P, González-Muniesa P, Prieto-Hontoria PL, Moreno-Aliaga MJ, Martínez JA. Lipoic acid improves mitochondrial function in nonalcoholic steatosis through the stimulation of sirtuin 1 and sirtuin 3. Obesity (Silver Spring). 2012 Oct;20(10):1974-83.

Dietary Fructose vs. Endogenous Fructose Production: Is The Aldose Reductase Mediated Production of Fructose to Blame for Diabesity & NAFLD? Plus: Could Amla Help?

Make you choice - cholesterol and regular sugar (left), or fat free and fructose-laden? In the end it all may not even matter.

When I stumbled upon a recent study from the University of Colorado a few days ago, my first thought was: Oh my! That sounds familiar. And indeed, if you know anything about the "cholesterol conundrum" you will probably feel reminded of the disconnect between cholesterol intake, cholesterol levels in the blood and cholesterol-related increases in cardiovascular disease risk - don't forget that this is still an issue, although it may neither be your dietary cholesterol or your total cholesterol levels that mediate the risk increases.

Looks like you cannot pick your poison, because whatever you chose, your body will produce what it considers fitting from it

According to the said study from the University of Colorado it does in fact seem that our current favorite villain, namely fructose, has more in common with its predecessor on the throne of "avoid at all costs nutritional evils", i.e. cholesterol, than we have previously thought.

Surprise! Some of you may have heard about it for the first time 8 days ago in the first serving of insulin-sensitizing supplements, here at the SuppVersity: Amla aka Emblica officinalis is a natural aldose reductase inhibitor (Pupalla. 2012) and would thus be qualified to keep the negative side effects of endogenous fructose production in check!

"Many high glycaemic foods also contain fructose. For instance, sucrose is a disaccharide of glucose and fructose, and high-fructose corn syrup is a mixture of glucose and fructose, raising the question of whether fructose is responsible for the effects of high glycaemic foods to increase the risk for metabolic syndrome. To further complicate this issue, fructose can be generated endogenously via the polyol pathway from glucose. Specifically, aldose reductase (AR) metabolizes glucose to sorbitol, which can then be converted to fructose by sorbitol dehydrogenase.

Thus, if AR were highly expressed or activated in the liver, some of the glucose absorbed might be converted to fructose, and hence possibly provide a mechanism for inducing features of the metabolic syndrome."

To render this a little more straight forward, let's get back to our cholesterol analogy: We know (or should know) that part of the reason that dietary cholesterol is not a danger / problem for us is a simple consequence of the fact that most of the cholesterol that's floating around in our blood is actually produced directly within our bodies. And for cholesterol the rule of thumb is: The less cholesterol we eat, the more we will be producing ourselves.

Do we sugar- / fruit-coat ourselves?

For fructose this should actually be different. After all, fructose is not of similar physiologic importance to us as cholesterol the "fatty acid shuttle" and steroid precursor. Still, necessary or not, at least the results of the study at hand appear to suggest that the mammalian body appears to like his fructose so much that it will just produce it on its own, even when the diet is fructose free.

Unforuntately, the consequences Lenaspa et al. observed, when they kept 4 groups of rodents (wild-type and fructokinase knockout (KO) mice, who cannot produce fructose from glucose) on diets with or without glucose (10% (wt/vol)) in the drinking water and compared the body compositional changes of these mice to a control group pm regular chow (containing 60% carbohydrate and no fructose), appear to suggest that this is exactly as bad as guzzling fructose corn syrup all day.

Figure 1 : When the aldose reductase enzyme is deactivated mice will gain significantly less weight and avoid both insulin resistance and NAFLD despite being on a high glucose (no sugar) diet (Lanaspa. 2013)

In fact, the absence of the enzymes that are necessary to do the conversion of glucose to fructose did not just lead to a major and significant reduction in weight gain, it also blunted the typical pro-non-fatty liver disease effects of high sugar diets and kept the insulin sensitivity of the knockout mice in the glucose group in check.

Figure 2: Fructose uptake (mmol/g tissue per min) increases with glucose concentration (mmol/L; Uhsijima. 1995)

"These studies suggest that under certain conditions glucose may induce metabolic syndrome in mice via an AR [=fructose production via aldose reductase], fructose-dependent pathway. Whether this is occurring in humans ingesting high glycaemic foods remains to be determined. However, as in mice, AR can be activated in humans by a number of ways, including by high glucose concentrations. Total parenteral nutrition, in which a 35% glucose solution is provided
by the vein, is associated with the development of fatty liver, andexperimental studies have shown that it is mediated by the glucose component of the infused fluids

Soft drinks containing high-fructose corn syrup also deliver markedly high-glucose solutions (4–6%) to the gut, and sucrose-containing soft drinks provide similar amounts of glucose after the sucrose is degraded in the intestine." (Lanaspa. 2013)

With these new results it becomes even more obvious why HFCS which is actually a mixture of glucose and fructose is particularly nasty. It will not only increase the absorption of fructose (see Figure 2), but also provide our bodies with the necessary substrate to top an already overabundant fructose intake off with endogenously fructose to create something even I, as an outspoken critic of the "fructose hypothesis of obesity" would say is part of the perfect obesogenic storm and could easily explain why soft drink intake is so closely associated with an increased risk for obesity, fatty liver and insulin resistance.

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Suggested read on the never-ending debate on the "fundamental difference" between glucose and fructose: "Glucose vs. Fructose and Their Effects on Glucose, Insulin & Fat Oxidation" | read more

Bottom line: No, the study at hand does not imply that HFCS is harmless (on the contrary it adds another reason it's poison), but it should remind all of us that an exuberant (but not an appropriate) glucose intake is not necessarily causing less damage than fructose. Consumed in high enough amounts it's going to set the fructose production machinery of our body in gear and will thus yield very similar metabolic problems as fructose itself, the current scape-goat for "all things metabolic syndrome".

If you want to make absolute sure you really mess yourself up, I do however strongly advice you add some saturated fats, preferentially palmitic acid, to maximize insulin resistance and make sure the glucose cannot be taken up by your muscle before it can either harm you directly, or after being converted to fuctose or triglycerides.

What? Oh yeah, you're right! That's what 90% of our fellow Westerners do. Eating a high fat, high carb diet and sitting around all day... well, I guess it's thus not the fructose from the one apple they consume per months that's to blame for their misery, is it?

References:  

• Lanaspa MA, Ishimoto T, Li N, Cicerchi C, Orlicky DJ, Ruzicky P, Rivard C, Inaba S, Roncal-Jimenez CA, Bales ES, Diggle CP, Asipu A, Petrash JM, Kosugi T, Maruyama S, Sanchez-Lozada LG, McManaman JL, Bonthron DT, Sautin YY, Johnson RJ. Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome. Nat Commun. 2013 Sep 11;4:2434.
• Puppala M, Ponder J, Suryanarayana P, Reddy GB, Petrash JM, LaBarbera DV. The isolation and characterization of β-glucogallin as a novel aldose reductase inhibitor from Emblica officinalis. PLoS One. 2012;7(4):e31399.
• Ushijima K, Riby JE, Fujisawa T, Kretchmer N. Absorption of fructose by isolated small intestine of rats is via a specific saturable carrier in the absence of glucose and by the disaccharidase-related transport system in the presence of glucose. J Nutr. 1995 Aug;125(8):2156-64.

Get Your Protein, Veggies & Fruits and Get Them Regularly: High(er) Meal Frequency (6 à Day) + High(er) Protein Diet Support Weight & Fat Loss on a Diet

There are more than six ways to get six-pack abs - trust me.

I guess, I am going to provoke a quarrel by claiming there may be advantages to eating more frequently. After all, saying anything that could be interpreted as criticism of intermittent fasting is about as unpopular as talking about the benefits of carbohydrates, these days. And I am guilty of doing both on a regular basis.

The optimal diet strategy? Trying what works best for you!

The latest reason for me to question that there is only one way to get ripped (and that this includes eating just one meal per day), is the publication of a study by Paul J. Arciero et al. who found that "Increased Protein Intake and Meal Frequency Reduces Abdominal Fat During Energy Balance and Energy Deficit" (Arciero. 2013)

To assess the effects of different dietary regimen, the scientists from the Skidmore College in  Saratoga Springs, the Florida State University in Tallahassee, the Colorado State University in Fort Collins and the Army Institute of Public Health. Recruited 30 individuals through newspaper advertisements and flyers.

A previous study by Dr. Bray showed: When all is said and done calories count | read more

"Participants were nonsmoking, healthy men and women with no known cardiovascular or metabolic diseases as assessed by a medical history and a comprehensive medical examination by their physicians.

All participants were inactive (<30 min, 2d/wk or structured physical activity), overweight or obese (BMI >30.36 +/- 5.9 kg/m²)), middle aged (46 years), and weight stable (62 kg) for at least 6 months prior to beginning the study." (Arciero. 2013)

The participants were then randomly assigned to a dietary interventions in the course of which they consumed their habitual diets for 5 days (this was meant to get a baseline reading), a balanced diet for 28 days and a diet with a negative energy balance (-25%) for another 28 days (see Figure 1 for macros).

"All nutrition plans for each group (TD3, HP3, and HP6) during BAL and NEG were similar in fat (20-25% total energy) and low in glycemic index (<50). It is important to highlight that the composition of all diets emphasized unprocessed, unrefined, high nutrient-density whole foods and were thus high in fruits, vegetables, unsaturated plant oils, and lean sources of protein.

Thermogenesis anyone? Suggested read: "MCT + Chili Make a Pretty HOT Pair: 50% Increase in Diet Induced Thermogenesis in Well-Controlled Human Trial" | read more

A 7-day menu plan was provided to all participants for the entire 62-day intervention. These meal plans included seven choices for each breakfast, lunch, and dinner (and mini-meals for HP6) that were modified for each person’s specific caloric needs and designed by a registered dietician (RD) using the Food Processor SQL Edition (version 10.7.0, ESHA Research, Salem,OR, 2010) using common foods [...] It is important to highlight that each individual meal consumed during the 28-day BAL and NEG phases was designed to deliver the same macronutrient distribution pattern as the overallnutritional plan for each group" (Arciero. 2013)

Irrespective of whether the energy content was balanced or negative (see Figure 1) the TD3 & HP3 diets contained only three meals. On the other hand, the HP6 diet with its six meals per day stands for the almost forgotten "eat more frequent meals to lose more fat" paradigm of the late 20th century.

Figure 1: Macronutrient composition (in g; left) and glycemic index + total calories (right) of the test diets (Arciero. 2013)

And if you look at the data in Figure 2 you will certainly agree that it may be worth asking, whether this set in stone paradigm of old-school bodybuilding diets was rightfully forgotten over the course of the past decade. At least for the guys and gals in the study at hand it did after all work quite nicely to consume a high(er) protein intake and high(er) meal frequency:

Figure 2: Body fat composition expressed relative control diet (left); Kcal expenditure / kcal intake (right; Arciero. 2013)

Ok, it's not like you could not get along with fewer meals, but the effects on body fat and muscle were significant and meal-frequency specific:

So can you? I mean, can you really get rid of hunger pangs by upping the protein content of your meals? Yes, you can, but as usual, there is a string attached, here. One of the infamous "on the other hands": "The Satiating Truth About Proteins and Why High Protein and Low Amounts of Low GI Carbs Don't Mix Well" | read more

"Given daily energy intake and expenditure were tightly controlled throughout the 62-day intervention and were similar among groups, differences in body composition may be due to changes in macronutrient distribution (%) of the diets and not to changes in total caloric intake or energy expenditure, as others have documented previously (Bray. 2012; Larsen 2010). Close attention was given to ensure that all participants consumed similar high-quality foods and only the ratio of macronutrients and frequency of meals consumed among the three groups differed. This novel finding highlights the benefits of HP6 in the absence of change in total macronutrient (kcal) intake on ABF loss and may have profound influence on public health policy regarding nutrient intake recommendations for adults."

Before you freak out and start curing, let me remind you that the results of the study at hand do not imply that there are no other ways to improve your body composition.

Improved diet-quality alone cuts body fat and increases postprandial thermogenesis

Moreover, my personal highlight of the study is not the effect of the meal frequency or the high protein content. My personal highlight is that the improvement in diet quality, which was brought about by the switch from the regular (control) diet (actually I was implied to write dirt instead of "diet) to a balanced diet that was high in fruits, vegetables, and lean sources of protein. That alone lead to a significant fat loss even in the "balanced" calorie intake period.

It was also this change in diet quality and not the praised increase in protein intake that brought about a significant increase in the thermogenic response to a meal by 30% - with the highest postprandial thermogenesis being observed in the TD3 group - the group with the lower protein intake (393kcal/90min, 353kcal/90min and 348kcal/90min in the TD3, HP3 and HP6 arm of the study)!

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Forget about the myth that only what you eat in the vicinity of your workout is going to help you build muscle - "Opening the "Anabolic Barn Door" With the Key of Exercise and Nutrition Science!" | read more

Bottom line: Eating a healthy diet is key. High protein (35% of total energy intake) and increased meal frequenccy can increase body recomposition effects of your diet, but neither works via increased thermogenesis. Intermittent fasting is not the only way of getting lean, but the study at hand does not show us that it is an inferior way either. Why? Well, we do not have the respective IF group with only 2 meals in a small time-window to "prove" that.

So assuming that you can control yourself, even if you are eating 24/7 (6 meals in 12-16h thats eating every 2-3h), give it a try - there is reason people have been swearing by the "6-meals-a-day approach" for decades, even if that's not a prevention in postprandial thermogenesis that renders it more effective (the latter fell to 260-270kcal in all three groups, when the total energy intake was restricted), but simply a more pronounced cumulative caloric deficit (see Figure 2, right).

In conjunction with the high(er) protein intake you can still eat a rather high amount of protein with each meal and could thus probably yield slight muscle sparing effects. Apropos: There is something else that's muscle sparing: Resistance training. This as well as other effects of exercise should be reason enough to be very careful about projecting the results of the study at hand 1:1 onto yourself. And I am saying that despite the fact that the superiority of a six-meal nutritional strategy in athletes (esp. when they are cutting) was actually one of the few more or less convincing findings of the (imho) most comprehensive paper that has been published on this issue up to now, the "International Society of Sports Nutrition Position Stand: Meal Frequency" (LaBounty. 2011)

References:

• Arciero PJ, Ormsbee MJ, Gentile CL, Nindl BC, Brestoff JR, Ruby M. Increased protein intake and meal frequency reduces abdominal fat during energy balance and energy deficit. Obesity (Silver Spring). 2013 Jul;21(7):1357-66.
• Bray GA, Smith SR, de Jonge L, et al. Effect of dietary protein content on weight gain, energy expenditure, and body composition during overeating: a randomized controlled trial.JAMA. 2012;307:47-55
• La Bounty PM, Campbell BI, Wilson J, Galvan E, Berardi J, Kleiner SM, Kreider RB, Stout JR, Ziegenfuss T, Spano M, Smith A, Antonio J. International Society of Sports Nutrition position stand: meal frequency. J Int Soc Sports Nutr. 2011 Mar 16;8:4.
• Larsen TM, Dalskov SM, van Baak M, et al. Diets with high or low protein content and glycemic index for weight-loss maintenance. N Engl J Med. 2010;363: 2102-2113

The Pistachio Manifesto: Antioxidant, Metal Chelator, DNA Protector, Anti-Cancer Agent, Bug Killer (incl. H. Pylori & Herpes Simplex) & More. Have You Been Missing Out?

This is not exactly what I was talking about, when I said "going nuts", but in this case it would actually qualify as "going pistachios" ;-)

Walnuts, almonds and Brazil nuts, these are the stars among the hard-shelled fruits people tend to go nuts about (all puns intended ;-). Pistachios, on the other hand, get very little love. I have in fact written about their surprisingly low effective energy content and their highly bioavailable phenolic content before (learn more), but what the myriad of phenols in these small nutritional powerhouses the ancient Egyptians used as incense, preservative and breath sweetener, while their Iranian neighbors in the North East already knew about their beneficial effects on digestive, hepatic and kidney health (Avicenna. 2008) can do for our health has not been covered here at the SuppVersity.

So what is it pistachios can do for you?

With their traditional use as a remedy for digestive, liver and kidney issues, you already have an idea where this could be heading. The shelled fruits of which we know that they have been part of the human diet for at least 9,000 years and that's cultivated in the Middle East, United States and Mediterranean can however do more for you:

• 

  Histidine happens to be an excellent chelator and potential weight loss adjuvant, as well (learn more)

  Potent antioxidants: Different parts and constituents from P. lentiscus  have been shown in vitro radical scavenging properties They protect your LDL molecules from being oxidized and will thus have direct beneficial effects on your atherosclerosis and overall heart disease risk (Holvoet. 2004).
• Metal chelators: A 2011 study by Orhan et al reports that pistachios (P. terebinthus fruits) are potent metal chelators (on par with EDTA) and have an impressive radical scavenging activity. Interestingly engough, the Antioxidant activity of the fruits actually seems to increase, when they are roasted (Orhan. 2012).
• DNA protection: More or less a downstream effect from the high content of antioxidant compounds, specifically gallic acid, digallic acid and 1,2,3,4,6-pentagalloylglucose, and polyphenols have direct protective effects on cellular DNA and pro-carcinogenic mutations.
• Antimicrobial activity (incl. anti H. Pylori): Certainly among the most interesting effects are the anti H.Pylori effects of α- pinene, a compound from the essential oils in pastachios (speficifally P.atlantica var. kurdica). Other ingredients, like verbenone, rterpineol, and linalool showed high antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus subtilis (Koutsoudak. 2005).
  
  

  

  You can battle H. pylori with probiotics, as well. If you want to learn more about this, I'd suggest you go back a couple of months and read the full story in the SuppVersity Short News from October 2012 (go for it)

  Sakami et al. report similar beneficial effects against pathologic bacteria (Porphyromonas gingivalis and Prevotella melaninogenica) antiplauqe activity on teeth by inhibiting bacterial growth in saliva (Sakagami. 2009). Özçelik et al. add noticeable anti-viral effects to the list of anti-microbial activities of pistachio species (Özçelik. 2005). The viruses tested in the study were Herpes simplex (DNA) and Parainfluenza viruses (RNA). The effects were significant for both Kernel and seed extracts.
• Anti-inflammatory activity: Extract of the resin of P. lentiscus var. Chia and its isolated phytosterol tirucallol exert direct anti-inflammatory effects on human aortic endothelial cells and inhibit the activity of adhesion molecules that express the inflammatory cytokine TNF-α (Tzakou. 2007). Tzakou et al. ascribe the effects to phytosterol that goes by the name if tirucallol - never heard of it? Me neither, but who knows on which supplement label you may find it in the future ;-)
• Digestive health: I already mentioned this in the introduction. One of the most important traditional uses of gums from Pistacio species is the management of gastrointestinal disorders; and that has been confirmed by several studies (Rahimi. 2009 & 2010; Farzaei. 2013). Resin of P. lentiscus has been shown to significantly reduced the intensity of gastric mucosal damage induced by pyloric ligation, aspirin, phenylbutazone, reserpine and restraint with cold stress  via its  antisecretory and cytoprotective activities (Al-Said. 1986)
  

  

  Figure 1: Improvements of acid regurgitation and heartburn in forty eight patients fulfilling Rome II criteria for functional dyspepsia were randomly assigned to receive either Pistachio var chia mastic gum 350 mg three times daily or placebo after three weeks (Dabos. 2009)

  A double- blind  placebo controlled trial, P. lentiscus gum lead to significant improvement of the symptoms of patients with functional dyspepsia  (Dabos. 2009). Extracts have been successfully tested in experimental models of acute colitis and IBS (Rahimi. 2013), and there is supporting evidence for beneficial effects of P. lentiscus var. chia resin in patients with established mild to moderate active crohn’s disease (CD) after 4 weeks of supplementation (Kaliora. 2007a,b).

• 

  Suggested read: Supplements to Preserve and Restore Insulin Resistance (read more)

  Antidiabetic activity: This is not about the nuts, but about a leaf extract, which has demonstrated significant acute postprandial  antihyperglycemic activity comparable to metformin and glipizide in starch-fed rats, in which it also lead to significant overall improvements in glucose tolerance (Kasabri. 2011). Unfortunately, a study by Kasibri et al. does not support these results - at least not for normoglycemic and streptozocin-induced hyperglycemic rats (Kasibri. 2004) on a regular diet.
  
  This would suggest that there is a direct correlation with carbohydrate intake, and voilá a 2007 human study confirmed that the gum, not the leaf extract can effectively, lower blood serum glucose levels in men... however, there is another "on the other hand attached here": this did not work for the female study participants (Triantafyllou. 2007).

• 

  The Protective Hull of These 61 Super Fruits Can Ward Off Cancer (more)

  Anti-cancer effects: In a relatively recent review of the literature, Giaginis & Theocharis call pistachio mastic gum a "conglomeration of effective anticancer drugs" (Giaginis. 2011) - probably not without reason, after all they cite a plethora of scientific data from peer-reviewed studies to support the anticancer activities of mastic gum and its major constituents and highlighting the various molecular mechanisms through which the triterpenoids work their anti-cancer magic.
  
  Rezaei et al., for example were able to show that the fruit extract of P. atlantica sub. kurdica exerts direct inhibitory effects on human colon carcinoma cells that was comparable to the drug Doxorubicin (Rezaei. 2012). Another example? Well what about the anti-breast cancer, anti liver-, anti cervical and anti skin-cancer effects of oleoresin (Almehdar. 2012)
• Hypolipidemic effects (=lowering high blood lipids): Extracts from P. vera  fruits have shown beneficial effects on HDL and LDL level in rabbit model of atherosclerosis, they exert positive effects on the lipid levels of patients with moderate hypercholesterolemia (Edwards. 1999). And have several animal studies to support their anti-artherogenic effects (e.g. Bakirel. 2003) 

Impressed? Well I'd hope so, after all this turned out to be more work than I initially thought, when I started to "just write a brief overview of the health effects of pistachios" ;-)

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Brazil nuts & selenium: "How much is too much?" A weighty question I addressed in a July 2013 SuppVersity article: "Brazil Nuts & Selenium: Are You Nuts If You Have More Than One Per Day?" (more)

Bottom line: Ok, I have to admit there is no scientific evidence that all the good things mentioned above are going to happen to you, if you have a handful of pistchios every other day, but you know what? It may still be a piece in the puzzle people often refer to as "healthy diet" - so if you are into nuts and can "afford" their relatively high energy content, go for it! After all, the above are only the "confirmed" effects.

Note: Actually everybody can "afford" eating nuts, it's more a question of being able to stop before the whole 500g family pack is annihilated... and trust me, if you love nuts, this can happen pretty fast, even if you have to shell them as it is the case with pistachios.  

Last but not least, in traditional Iranian medicine, certain ingredients in pistachios are known to exhibit various additional pharmacological activities incuding diuretic, lithontripic, anti-tussive, anti-rheumatic, anti-asthmatic, anti-hypertensive, and aphrodisiac effects of which Bozorgi et al. point out that the "are not [yet] supported by any current scientific documents and so, they could be considered  for investigating by researchers." (Bozorgi. 2013)

References:

• Almehdar H, Abdallah HM, Osman AM, Abdel-Sattar EA. In vitro cytotoxic screening of selected Saudi medicinal plants. J Nat Med. 2012 Apr;66(2):406-12.
• Al-Said MS, Ageel AM, Parmar NS, Tariq M. Evaluation of mastic, a crude drug obtained from Pistacia lentiscus for gastric and duodenal anti-ulcer activity. J Ethnopharmacol. 1986 Mar;15(3):271-8.
• Avicenna.The canon. Translated by: A . Shrafkandi. Soroush Press, Tehran. 2008.
• Bakirel T. The Investigation of the Effects of Pistacia terebinthus L. Upon Experimentally
  Induced Hypercholesterolemia and Atherosclerosis in Rabbits. Turk. J. Vet. Anim. Sci. 2003; 27: 1283- 1292.
• Bozorgi M, et al. Five Pistacia  species (P. vera, P. atlantica, P. terebinthus, P. khinjuk and P. Lentiscus): A review of their traditional uses, phytoche mistry and pharmacology. The Scientific World Journal. 2013.
• Dabos KJ, Sfika E, Vlatta LJ, Frantzi D, Amygdalos GI, Giannikopoulos G. Is Chios mastic gum effective in the treatment of functional dyspepsia? A prospective randomised double-blind placebo controlled trial. J Ethnopharmacol. 2010 Feb 3;127(2):205-9.
• Edwards K, Kwaw I, Matud J, Kurtz I. Effect of pistachio nuts on serum lipid levels in patients with moderate hypercholesterolemia. J Am Coll Nutr. 1999 Jun;18(3):229-32.
• Farzaei R et al. An evidence-based review on medicinal plants used for the treatment of peptic ulcer in traditional Iranian medicine, Int J Pharmacol. 2013 [ahead of print]
• Giaginis C, Theocharis S. Current evidence on the anticancer potential of Chios mastic gum. Nutr Cancer. 2011 Nov;63(8):1174-84.
• Holvoet P. Oxidized LDL and coronary heart disease. Acta Cardiol. 2004 Oct;59(5):479-84. Review.
• Orhan IE et al. Neuroprotective potential of some terebinth coffee brands and the unprocessed fruits of Pistacia terebinthus L. and their fatty and essential oil analyses. Food Chemistry. 15 February 2012; 130(4):882–888.
• Özçelik B, Aslan M, Orhan I, Karaoglu T. Antibacterial, antifungal, and antiviral activities of the lipophylic extracts of Pistacia vera. Microbiol Res. 2005;160(2):159-64. 
• Kaliora AC, Stathopoulou MG, Triantafillidis JK, Dedoussis GV, Andrikopoulos NK. Chios mastic treatment of patients with active Crohn's disease. World J Gastroenterol. 2007a Feb 7;13(5):748-53.
• Kaliora AC, Stathopoulou MG, Triantafillidis JK, Dedoussis GV, Andrikopoulos NK. Alterations in the function of circulating mononuclear cells derived from patients with Crohn's disease treated with mastic. World J Gastroenterol. 2007b Dec 7;13(45):6031-6.
• Kasabri V, Afifi FU, Hamdan I. In vitro and in vivo acute antihyperglycemic effects of five selected indigenous plants from Jordan used in traditional medicine. J Ethnopharmacol. 2011 Jan 27;133(2):888-96.
• Koutsoudaki C, Krsek M, Rodger A. Chemical composition and antibacterial activity of the essential oil and the gum of Pistacia lentiscus Var. chia. J Agric Food Chem. 2005 Oct 5;53(20):7681-5.
• Rahimi R, Mozaffari S, Abdollahi M. On the use of herbal medicines in management of inflammatory bowel diseases: a systematic review of animal and human studies. Dig Dis Sci. 2009 Mar;54(3):471-80.
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