Letter to the Editor
Correcting a misrepresentation of Hypervitaminosis A attributed
to herbalife product consumption
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
2. No symptoms associated with vitamin A toxicity were observed.
3. Despite surgical intervention to insert a bile duct stent, the im-
provement 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.,
vitamin A according to
our own calculation
vitamin A plus
limit for preformed
Vitamin A by IOM
5082 2917 3417 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
Speciﬁcally, 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
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 consump-
tion 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
In this report, the liver biopsy of this individual did not ﬁtthe
usual biochemical pattern of hypervitaminosis A, which includes
ﬁbrosis. Furthermore, according to Kaplowitz and DeLeve (2003),
the chronicity of the ﬁbrosis process that is initiated with
hypervitaminosis A consumption is not typically inﬂuenced 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
In summary, the collective evidence does not support the theory
that chronic consumption of vitamin A from any source was causally-
linked 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.
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.,
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), 324–325.
Shils, M.E., Olson, J.A., Shike, M., Ross, A.C. (Eds.), 1999. Modern nutrition in health and
disease, 9th ed. Williams & Wilkins, Philadelphia.
Experimental and Molecular Pathology 90 (2011) 320–321
0014-4800/$ –see front matter © 2011 Elsevier Inc. All rights reserved.
Contents lists available at ScienceDirect
Experimental and Molecular Pathology
journal homepage: www.elsevier.com/locate/yexmp
Casey R. Smith
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: email@example.com (Y.S. Henig).
5 January 2011
Available online 20 February 2011
321Letter to the Editor