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Experimental and Molecular Pathology 90 (2011) 320321

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Experimental and Molecular Pathology

j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / y e x m p

Letter to the Editor

Correcting a misrepresentation of Hypervitaminosis A attributed to herbalife product consumption nonfat milk as directed, the daily consumption of preformed vitamin A would total 3417 IU, which is approximately 68% of the FDA DV, and is much less than the Tolerable Upper Limit (UL) for preformed vitamin A, which has been set at 10,000 IU by the Food and Nutrition Board (FNB) of the Institute of Medicine (IOM) (Hathcock, 2004). Two tablets of Formula 2 Multivitamin Complex also contain 1667 IU of provitamin A, in the form of beta-carotene. This distinction is important as there is no evidence that conversion of beta-carotene to vitamin A contributes to vitamin A toxicity, even when beta-carotene is ingested in large amounts (Shils et al., 1999). In fact, the Observed Safe Limit (OSL) for beta-carotene has been set at 25 mg per day for non-smokers, which would correspond to the equivalent of 41,666.7 IU of vitamin A. To suggest that consumption of vitamin A, at or below RDA recommended levels, would put any consumer at risk of developing hypervitaminosis A is contrary to the collective wisdom that formed the basis for their development. In this report, the liver biopsy of this individual did not t the usual biochemical pattern of hypervitaminosis A, which includes brosis. Furthermore, according to Kaplowitz and DeLeve (2003), the chronicity of the brosis process that is initiated with hypervitaminosis A consumption is not typically inuenced by abrupt vitamin discontinuation. This is in sharp contrast to the results reported in this paper, which attributes the full and gradual resolution of symptoms to withdrawal of Herbalife products over a two month period of time during which a biliary stent was in place. Also, the authors failed either to obtain or report hepatic vitamin A level, which would have been a useful tool to support their theory of hypervitaminosis A as a causative agent in this case report. In summary, the collective evidence does not support the theory that chronic consumption of vitamin A from any source was causallylinked to the reported case of intra-hepatic cholestasis in this individual. The authors' calculation of 5082 IU of preformed vitamin A is incorrect. The actual total amount of preformed Vitamin A consumed was 3417 IU, from Herbalife products and nonfat milk, which is below the FDA DV. To further speculate and extrapolate the root cause to then be causally linked to vitamin A intake exclusively provided through consumption of Herbalife products is simply not supported by the facts.

Keywords: Herbalife Hypervitaminosis A Liver Hepatotoxicity

In the Volume 88, Issue 2, April 2010 edition of this journal, a report was published which associated a rare case of intra-hepatic cholestasis in a 46-year-old male who was using Herbalife products. Herbalife products included one daily Formula 1 Shake, which is a food product, and two tablets of Formula 2 Multivitamin Complex, a dietary supplement (Ramanathan et al., 2010). The authors of this paper concluded that that the contribution of vitamin A from Herbalife products was the causative agent for the reported liver condition. We strongly question the authors' conclusion for the following reasons: 1. Preformed vitamin A in Herbalife products, as consumed, did not exceed the Food and Drug Administration Daily Value (DV) of 5000 IU. 2. No symptoms associated with vitamin A toxicity were observed. 3. Despite surgical intervention to insert a bile duct stent, the improvement in the liver condition was solely attributed to the Herbalife product dechallenge. As can be seen in the table below, the authors' calculation of 5082 IU of preformed vitamin A is incorrect.
Calculated vitamin A as reported by Ramanathan et al., 2010 (IU) 5082 Calculated preformed vitamin A according to our own calculation (IU) 2917 Preformed vitamin A plus milk added (IU) 3417 Tolerable upper limit for preformed Vitamin A by IOM (IU) 10,000

In reality, the contribution of relevant sources of vitamin A (including preformed vitamin A as retinyl palmitate and retinyl acetate), according to the reported product use of one Formula 1 shake and two tablets of Formula 2 Multivitamin Complex, is 2917 IU. Specically, 1250 IU of preformed vitamin A is included in the Formula 1 shake, and 1667 IU of preformed vitamin A is included in two tablets of Formula 2 Multivitamin Complex. If the Formula 1 shake is prepared with 8 oz of nonfat milk, the vitamin A contribution from milk is approximately 500 IU. Therefore, when prepared with

References
Hathcock, J.N., 2004. Vitamin and Mineral Safety, 2nd. Edition. Council for Responsible Nutrition, Washington DC. Kaplowitz, N., DeLeve, L.D., 2003. Drug-induced Liver Disease. Marcel Dekker, Inc., New York. Ramanathan, V.S., Pham, B.V., French, S., Hensley, G., Eysselein, V., Chung, D., Reicher, S., 2010. Hypervitaminosis A inducing intra-hepatic cholestasis a rare case report. Exp. Mol. Path. 88 (2), 324325. Shils, M.E., Olson, J.A., Shike, M., Ross, A.C. (Eds.), 1999. Modern nutrition in health and disease, 9th ed. Williams & Wilkins, Philadelphia.

0014-4800/$ see front matter 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.yexmp.2011.02.001

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Letter to the Editor 321

Ezra Bejar Casey R. Smith Kristy Appelhans Y. Steve Henig Herbalife International, USA Corresponding author at: Herbalife International, 800 W. Olympic Blvd., Los Angeles, CA 90015, USA. Fax: +1 213 765 9806. E-mail address: steveh@herbalife.com (Y.S. Henig). 5 January 2011 Available online 20 February 2011