Wednesday, June 13, 2012

Zinc: 15mg Are Plenty - After 120 Days Rodents on Diets Containing 2xRDA of Zinc Develop Metabolic Syndrome

Image 1 (scipop): Physicists and battery specialists know that copper and zinc make a galvanizing couple. If you put too much copper into your "battery" it will however stop working.
A recently published study from the Panjab University in India clearly suggests that doubling or quadrupling your zinc intake, a common practice in the health and fitness community, could do more harm than good. After only 4 months on a low phytate, high zinc diet (2x or 4x more zinc than in the standard chow), the rodents in the medium and high zinc intake goups showed a couple of unsettling metabolic changes (Taneja. 2012):
  • 20-40% increase in food intake
  • 20% increased body weight
  • 2x or 2.7x elevated blood sugar
  • 3.75x or 6x elevated insulin levels
  • 100% increase in cortisol
  • 2x or 2.5x elevated leptin levels
In short, while the Wistar rats that consumed the basal diet with the "rodent RDA" of 20mg zing per kg diet (0.53mg/day, 1mg/kg; HED ~0.17mg/kg or 8014mg/day) those with a two (human equivalent: 30mg) or four times (HED: 60mg/per) higher intakes developed all the classic symptoms of the metabolic syndrome
  • insatiable hunger despite overabundant energy intake
  • uncontrolled weight-gain => obesity
  • high blood sugar, insulin resistance => type II diabetes
  • constantly elevated cortisol levels
  • leptin resistance
Interestingly, these highly undesirable effects of long-term were precipitated by profound morphological changes in the structure of the mucosal epithelial cell layer of the intestine:
Figure 1: Mean microvillus height and number/unit surface area of mucosal epithelial cell of intestine in normal zinc (control) or high zinc groups (Taneja. 2012)
The TEM studies of intestinal segment revealed a significant increase in the absorption surface area of the absorptive mucosal epithelial cells. It was reflected as increase in mean height and number/ unit surface area of the microvillus (figure 1). Their mean height (nm) was calculated as 506.1 ± 2.30 in control group-I, 749 ± 1.22 in group-II and 942 ± 1.30 in group-III. Their  number/unit surface area (µm) was found to be 10.4 ± 0.51 in group-I, 13.2 ± 0.33 in group-II and 15.4 ± 0.36 in group-III (figure 1).

The increases in height and number/unit surface area were suggestive of increased capability of the intestine to absorb the nutrients per unit area than the control group-I.
Now what is interesting about these observations is not just that it is 100% logical (at least for a physicist like me) that an increase in epithelial surface area will increase the nutrient absorption, but also that scientists knew about them and their beneficial side-effects in people with Crohn's disease, a damaged  or "leaky" gut all along (Sturniolo. 2001) and still nobody ever even thought about the downsides of subsequently increased nutrient assimilation. Instead, it was once again simply concluded that what helps the sick, obese and pre-diabetic cannot hurt normal people - and that despite the absence of ample evidence for consistent beneficial effects of  zinc supplementation as a protective, let alone curative means in sick people (Beletate. 2007), or zinc (+ magnesium) supplementation in athletes (Wilborn. 2004)

Double or quadruple your zinc intake, avoid phytates and turn from athletic to diabetic!?

Figure 2: After only 120 days the rodent in the high zinc groups exhibited all the typical symptoms of the metabolic syndrome (Taneja. 2012)
In view of the fact that still way too many gymrats adhere to the false belief that a zinc supplement (just like a "high performance" multivitamin) was an absolute staple supplement everybody striving to build a better physique should consume, it is no wonder that supplement vendors like to put copious amounts of this cheap ingredient into their products. Even if you are cheap (or smart) and avoid buying one of the "performance" multis, the 15mg of zinc every standard multi has plus the 30-50mg of your "nightly" ZMA, would take you right into the danger zone and even beyond and assuming that you follow another currently often proffered advice, which is to avoid phytate containing foods like a plague, your additional dietary zinc intake would probably get you right into the 60mg/day zone, which was so detrimental to the metabolic health of the rodents in the Tenja study.

In the defense of zinc supplements it should yet be mentioned that the chow the rodents were fed in the course of the experiment was not exactly what you, as an educated SuppVersity students would consider healthy, let alone "optimal". After all the diet was deliberately composed of "semi-synthetic" ingredients such as refined sucrose instead of the regular "grainy" pallets you would find in standard rodent chow, "to rule out the possibility of Zn-interaction with fibres and phytates" (Taneja. 2012), so that it would not take so long for the effects of the exuberant zinc intake to manifest.

"But my ZMA works! I feel so much better on it and if I drop my multi I get sick!"

"Artificial diet, rodent study, no real world implications", I hear ya! A 2004 study by Xiang et al. is yet only one out of many examples which suggest that you should not be so sure that will get away with taking your zinc-laden "staple supplements" (and in the case of the "multi" not just because of the zinc) for years: Increased lipid oxidation after 2 weeks, and increases in total cholesterol, triglycerides, LDL-C, ApoB100 and decreased in HDL and ApoA1 after 8 weeks of 50mg zinc per day in formerly healthy men are likewise clear indices of developing metabolic syndrome (Xiang. 2004). A result, by the way, that does not stand in contrast to studies on the effects of dietary zinc intake on glucose management such as Kanoni et al. (2011), where the highest dietary zinc intake of all subjects was 12.4mg (!) and thus still below the RDA and right on par with what the "average" American gets from his junkfood diet and supplements (see figure 3)!
Figure 3: I would not hope that you are eating like the "average American", are pre-diabetic and / or obese, but the data from the NHANES study is another puzzle to the picture that explains why Mr./Mrs. Average's health may benefit, while yours may suffer from supplemental zinc - they just don't get enough in their diet (Briefel. 2000)
If you are not constantly wreaking havoc on your gut lining and want it to regrow, are obese or diabetic (we do have some studies that suggest that at least in certain subgroups supplemental zinc can ameliorate this condition, yet mostly at the expense of higher insulin levels), you may want to reconsider if those staples of yours are really necessary, at least beneficial or maybe detrimental to the way you look feel and perform. And in the, as the guy at your local supp store would probably say, "totally improbable" case that despite taking all the staples he recommended, your blood glucose levels are getting out of whack, your cortisol is skyrocketing and your HDL is plummeting towards zero, you better not take his advice that all that will resolve once you introduced the latest (R-)ALA based nutrient partitioner into your supplement regimen (cf. "Lean & Muscular With Alpha Lipoic Acid?" ;-)

  1. Briefel RR, Bialostosky K, Kennedy-Stephenson J, McDowell MA, Ervin RB, Wright JD. Zinc intake of the U.S. population: findings from the third National Health and Nutrition Examination Survey, 1988-1994. J Nutr. 2000 May;130(5S Suppl):1367S-73S.
  2. Beletate V, El Dib RP, Atallah AN. Zinc supplementation for the prevention of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005525. Review. 
  3. Kanoni S, et al. Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis. Diabetes. 2011 Sep;60(9):2407-16.
  4. Taneja SK, Jain M, Mandal R, Megha K. Excessive zinc in diet induces leptin resistance in Wistar rat through increased uptake of nutrients at intestinal level. J Trace Elem Med Biol. 2012 Jun 8.
  5. Sturniolo GC, Di Leo V, Ferronato A, D'Odorico A, D'Incà R. Zinc supplementation tightens "leaky gut" in Crohn's disease. Inflamm Bowel Dis. 2001 May;7(2):94-8.
  6. Wilborn CD, Kerksick CM, Campbell BI, Taylor LW, Marcello BM, Rasmussen CJ, Greenwood MC, Almada A, Kreider RB. Effects of Zinc Magnesium Aspartate (ZMA) Supplementation on Training Adaptations and Markers of Anabolism and Catabolism. J Int Soc Sports Nutr. 2004 Dec 31;1(2):12-20. 
  7. Xiang Y, Yang X, Bian J, Wang L. [Effects of high level Zn intake on metabolism in man]. Wei Sheng Yan Jiu. 2004 Nov;33(6):727-31.