DR. MICHAEL HOLICK
of Medicine, Physiology and Biophysics
Director of the General Clinical Research Center
Director of the Bone Health Care Clinic
BOSTON UNIVERSITY MEDICAL CENTER
For more information click on a topic area below
CONTRIBUTIONS TO ENDOCRINOLOGY
||DEGREE (if applicable)
||FIELD OF STUDY
|Seton Hall, New Jersey
1971-75 Research Associate; Depart. of Biochemistry, University of Wisconsin,
1975-76 Research Associate, Endocrine Unit, Massachusetts General Hospital,
1976-78 Intern, Resident, and Clinical Fellow in Medicine, Massachusetts General
Hospital, Boston, MA
Professor of Medicine, Harvard Medical School; Assistant in Medicine,
Massachusetts General Hospital
1981-85 Associate Professor of Medicine, Harvard Medical School
1981-85 Associate Professor of Nutritional Biochemistry, Massachusetts Institute
of Technology, Cambridge, MA
1985-87 Professor of Physiology, Medicine, and Nutrition Tufts University;
USDA/Nutrition Research Center on Aging
1986-93 Chief, Endocrine Unit; Boston City Hospital, Boston, MA
1986- Director, General Clinical Research Center and Director Osteoporosis
Diagnostic Center, Boston University, School of Medicine, Boston, MA
1987-2004 Professor of Medicine, Physiology, and Dermatology, Boston University
School of Medicine
1993-2000 Chief, Section of Endocrinology, Nutrition and Diabetes, Boston
2004- Professor of Medicine, Physiology and Biophysics, Boston University School
1972 Wilson S. Stone Memorial Award, M.D. Anderson Hospital, Houston, TX
1980 Fuller Albright Young Investigator Award
1981 Ten Outstanding Young Leders Award
1983 Mead Johnson Award, American Institute of Nutrition
1985 Pisa Medalion for Excellence in Science, Pisa, Italy
1986 Merit Award, National Institutes of Health
1986 Stanley S. Bergan Award for excellence in the medical field, Seton Hall
1989 Arnold-Rickle-Prize for research in UV radiation and vitamin D metabolism
1989 Duhring Lecture in Dermatology
1991 Osborne and Mendel Award, American Institute of Nutrition
1994 E.V. McColIum Award, American Society for Clinical Nutrition
1995 Second Annual Beaudette-Thompson Lecture, Rutgers University
2000 American Skin Association's Psoriasis Research Achievement Award
2002 American College of Nutrition’s ACN Award
2003 Robert H Herman Memorial Award in Clinical Nutrition, American Society for
||Holick MF, DeLuca HF.
A new chromatographic system for vitamin D3 and its metabolites: Resolution
of a new vitamin D-3 metabolite. J. Lipid Res. 1971; 12:460-465.
||Holick MF, Schnoes HK,
DeLuca HF. Identification of 1,25-dihydroxycholecalciferol, a form of
vitamin D3 metabolically active in the intestine. Proc Natl Acad Sci. USA.
||MacLaughlin JA, Gange
W., Taylor D, Smith E, and Holick MF. Cultured psoriatic fibroblasts from
involved and uninvolved sites have a partial but not absolute resistance to
the proliferation-inhibition activity of 1,25-dihydroxyvitamin D3. Proc Natl
Acad Sci 1985; 82:5409-5412.
||Holick, M.F., Ray, S.,
Chen, T., Tian, X., and Persons, K. Novel functions of a parathyroid hormone
antagonist: stimulation of epidermal proliferation and hair growth in mice.
Proc Natl Acad Sci 91:8014-8016, 1994.
||Schilli, M.B. Ray, S.,
Paus, R., Obi-Tabot, E. and Holick, M.F. Control of hair growth with
parathyroid hormone (7-34). J. Invest. Dermatol. 108:928-932, 1997.
||Krause, R., Buhring,
M. Hopfenmuller, W., Holick, M.F. and Sharma, A.M. Ultraviolet B and blood
pressure. Lancet 352:709-710, 1998.
||Perez, A., Chen, T.C.,
Turner, A., Raab, R., Bhawan, J., Poche, P., and Holick, M.F. Efficacy and
safety topical calcitriol (1,25-dihydroxyvitamin D3) for the treatment of
psoriasis. Br. J. Dermatol. 134:238-246, 1996.
Whitlatch, L.W., Chen T.C., Lokeshwar, B.L., and Holick, M.F. Human prostate
cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3. Cancer
Epidemiology, Biomarkers & Prevention 7:391-395, 1998.
||Kong, X.F., Zhu, X.H.,
Pei, Y.L., Jackson, D.M., and Holick, M.F. Molecular cloning,
characterization, and promoter analysis of the human 25-hydroxyvitamin
D3-1- hydroxylase gene. Proc. Natl. Acad. Sci. USA 96:6988-6993, 1999.
||Tian, X.Q., and Holick,
M.F. a liposomal model that mimics the cutaneous production of vitamin D3. J
Biol Chem 274:4174-4179, 1999.
Flanagan, J.N., Whitlatch, L.W., Tseng, C.C., Chen, T.C., Holt, P.R., Lipkin,
M.S., and Holick. 25-Hydroxyvitamin D-1α-hydroxylase in normal and malignant
colon tissue. Lancet 357:1673-1674, May 26, 2019.
Whitlatch, L.W., Chen, T.C., Zhu, X.H., Holick, M.T., Kong, X., and Holick,
M.F. Enhancing 1,-hydroxylase activity with the 25-hydroxyvitamin D-1-hydroxylase
gene in cultured human keratinocytes and mouse skin. J. Invest. Dermatol.
||Peters, Eva, M.J.,
Foitzik, K., Paus, R., Ray, S., and Holick, M.F. A new strategy for
modulating chemotherapy-induced alopecia, using PTH/PTHrP receptor agonist
and antagonist. J. Invest. Dermatol. 117:173-178,2001.
Young, M.V., Schwartz, G., Flanagan, J., Burnstein, K., Lokeshwar, Bal L.,
Rich, E., Holick, M.F., and Chen, T.C. 25-Hydroxyvitamin D-1-hydroxylase
activity is diminished in human prostate cancer cells and is enhanced by
gene transfer. Steroid Biochem & Molecul Biol 81:135-140, 2002.
Koutkia, P., Rieke, S.M., Chen, T.C., Perez, A., and Holick, M.F.
Fortification of orange juice with vitamin D: A novel approach to enhance
vitamin D nutritional health. Am J Clin Nutr , 77:1478-83, 2003.
||Holick, M.F., Chimeh,
F.N., and Ray, S. Topical PTH (1-34) is a novel, safe and effective
treatment for psoriasis. Br J Dermatol 149:370-376, 2003.
||Holick, M.F., Chimeh,
F.N., and Ray, S. Topical PTH (1-34) in a novel, safe and effective
treatment for psoriasis. Br Jl Dermatol 149:370-376, 2003.
||Moore, C., Murphy, M.M.,
Keast, D.R., and Holick, M.F. Vitamin D intake in the United States. J Am
Diet Assoc 104:980-983, 2004.
||Durakovic, C., Ray,
S., and Holick, M.F. Topical paricalcitol (19-nor-1α,25-dihydroxyvitamin D2)
is a novel, safe and effective treatment for plaque psoriasis: a pilot
study. Brit J Dermatol 151:190-195, 2004.
||Tangpricha, V. Turner,
A., Spina, C., Decastro, S., Chen, T., and Holick, M.F. Tanning is
associated with optimal vitamin D status (serum 25-hydroxyvitamin D
concentration) and higher bone mineral density. Am J Clin Nutr 80:1645-1649,
||Holick, MF and
Jenkins, M. The UV Advantage, iBooks:New York, 2004.
Tangpricha, V., Weinberg, J., Malbanan, A., Chimeh, F., and Holick, M.F.
Comparison of the effects of a novel conjugated oral estrogen,
estradiol-3β-glucoside, with oral micronized 17β-estradiol in postmenopausal
women. Menopause (Submitted).
||Spina, C., Tangpricha,
V., Min, Y., Zhou, W., Wolfe, M., Maehr, H., Uskokovic, M., Adorini, L., and
Holick, M.F. Colon cancer and ultraviolet B radiation and prevention and
treatment of colon cancer in mice with vitamin D and its Gemini analogues. J
Steroid Biochem Molecular Biol. (Submitted)
CONTRIBUTIONS IN ENDOCRINOLOGY
1. Vitamin D3 Metabolism
Dr. Holick’s first contributions in the field of vitamin D nutrition occurred
while he was a graduate student with Dr. Hector DeLuca at the University of
Wisconsin. Dr. Holick isolated and identified 25-hydroxyvitamin D3 from human
blood and was the first to isolate and identify the biologically active form of
vitamin D3 as 1,25-dihydroxyvitamin D3. For his creative work, he received
several awards outlined in the Biography and his achievement was considered as
one of the Landmarks in research and featured in the Journal of National
Institutes of Health Research in 1992.He played a key role in the first chemical
synthesis of 1,25-dihydroxyvitamin D3 and its 25-deoxy analog 1α-hydroxyvitamin
D3 that are used to treat renal osteodystrophy and vitamin D dependent rickets
type I. He carried out the seminal investigations on the regulation of the renal
synthesis of 1,25-dihydroxyvitamin D3 by parathyroid hormone, calcium, and
phosphorus. He also helped pioneer the development of the 25(OH)D and 1,25(OH)2D
assays for clinical use.
2. Photobiology of Vitamin D
He established how sunlight produces vitamin D3 in human skin and how it is
photodegraded thereby preventing vitamin D intoxication due to prolonged
excessive exposure to sunlight. He established that aging, sunscreens, skin
pigmentation decrease the capacity of human skin to produce vitamin D. He
designed a clever model system to evaluate the effect of latitude, season, and
time of day on the cutaneous production of vitamin D3 and found that latitude,
season, and time of day all dramatically influenced the cutaneous production of
vitamin D3. He observed for the first time that exposure to sunlight in the
winter at latitudes above and below 40º north and south, respectively, did not
result in any production of vitamin D3. This provided important information for
dietary intake requirements for vitamin D in the winter especially for children
and adults who are prone to developing vitamin D deficiency.
3. Effect of body fat composition and vitamin D
It is well known that obesity is associated with vitamin D deficiency. He
speculated that vitamin D either coming from the skin or the diet would be so
efficiently stored in the body fat that it would be less bioavailable in obese
people. To test this hypothesis he recruited obese and normal weighted adults
and exposed them to the same amount of simulated sunlight or gave them an oral
dose of 50,000IU of vitamin D. He observed a marked reduction in the peak blood
levels of vitamin D and 25(OH)D in the obese subjects that were exposed to
simulated sunlight or took an oral dose of vitamin D2 when compared to normal
weighted controls. These results provide strong evidence that obese individuals
require a higher vitamin D intake in order to satisfy their body’s vitamin D
requirement, because their large body fat stores most of the cutaneously
produced and orally ingested vitamin D.
4. Role of 1,25-Dihydroxyvitamin D3 in Human Skin
In the early 1980s, Dr. Holick observed that human skin possessed the receptor
for 1,25-dihydroxyvitamin D3. In pioneering studies, he showed that
1,25-dihydroxyvitamin D3 inhibited proliferation and induced terminal
differentiation of cultured human keratinocytes. He introduced the concept that
activated vitamin D compounds could be used for the treatment of the
hyperproliferative skin disorder psoriasis. He initiated one of the first
clinical trials to demonstrate the therapeutic efficacy and safety of topically
administered 1,25-dihydroxyvitamin D3 for the treatment of psoriasis. These
observations have led to the worldwide use of 1,25-dihydroxyvitamin D3 and its
analogs for treating this stubborn skin disease.
5. Redefining Vitamin D Insufficiency
It has been long suspected that the normal range for the 25 (OH) D assays, which
is the gold standard for determining vitamin D status of patients, was
inadequate to identify patients at risk for vitamin D deficiency. Dr. Holick
initiated a study whereby he took healthy adults who had serum 25(OH)D that was
considered to be in the low normal range (normal range for 25(OH)D is 10 to 55
ng/ml) from 11 ng/ml to 25 ng/ml and gave then 50,000 IU of vitamin D once a
week for eight weeks. He measured their serum 25(OH)D and PTH values. He
reasoned that if the PTH values declined in response to the vitamin D therapy,
this would be an excellent indicator that the subject was not vitamin D
sufficient. After treatment, the 25(OH)D levels increased by 109% and PTH levels
decreased by 22%. When stratified to pretreatment 25(OH)D levels, PTH decreased
by 35% for subjects with 25(OH)D between 11 and 15 ng/ml (55% of these healthy
adults were found to have elevated PTH levels) and 26% for adults with 25(OH)D
between 16-20 ng/ml (35% had secondary hyperparathyroidism). Adults who had
25(OH)D levels between 21 –25 ng/ml had no significant change in their PTH
levels even though their 25(OH)D increased by 66%. These results provide strong
evidence that serum 25(OH)D levels need to be at least 21 ng/ml for the body to
be vitamin D sufficient.
6. Adequacy of Vitamin D Fortification of Milk
In the early 1990s, Dr. Holick was asked to evaluate an elderly patient with
hypercalcemia and vitamin D intoxication. A thorough evaluation did not reveal a
medicinal source for the vitamin D intoxication. Two weeks later he was asked to
evaluate the cause of vitamin D intoxication in a young child at the Boston
Children’s Hospital. Once again, no obvious cause was apparent. However, these
two apparently unrelated outbreaks of vitamin D intoxication prompted Dr. Holick
to investigate the cause of the vitamin D intoxication. A survey was developed
and circulated to physicians throughout the Boston area. He and his colleagues
identified eight additional cases of vitamin D intoxication. The common
denominator amongst all of the affected individuals was that they drank milk
from the same local dairy. Using the vitamin D assay that he had developed, he
purchased milk from the dairy and brought it back to his laboratory for an
analysis of vitamin D. He found that the milk had in excess of 600 times more
vitamin D than stated on the label. He informed the Department of Public Health
about these findings and only after his repeated warnings did the DPH act and
investigated the dairy. At the same time, he decided to evaluate the vitamin D
content in milk produced by milk processors throughout the US and western
Canada. He found that no more than 20% of milk samples produced by most of the
major milk processors contained within 20% of the 400 IU that was suppose to be
in the milk. He also observed that between 15 and 20% of skim milk samples
contained no detectable vitamin D. Thus, he and his colleagues showed that milk
cannot be depended on as a sole source of vitamin D to satisfy the body’s
7. Novel Fortification of Orange Juice with Vitamin D
Since many adults do not drink milk and therefore do not avail themselves of the
vitamin D nutritional content of this fortified product, there continues to be a
need to find alternative foods that can be safely and effectively fortified with
vitamin D. Dr. Holick’s laboratory evaluated the effect of the fat content in
milk on vitamin D bioavailability. They observed that vitamin D absorption from
milk was equally effective whether it was present in whole milk or skim milk
Since orange juice is now routinely fortified with calcium, vitamin E and C, he
considered the possibility of fortifying orange juice with vitamin .He conducted
a study and observed in healthy young and middle-aged adults that vitamin D was
highly bioavailable and raised blood levels of 25-hydroxyvitamin D more than
two-fold, compared to adults who drank the same orange juice that was not
fortified with vitamin D. These observations have provided the impetus for the
food industry to consider fortifying orange juice with vitamin D. This new
fortification process will have important health implications for vitamin D
nutrition for the general population.
8. Function of Vitamin D in Regulating Cell Growth
It is well documented that there is a latitudinal effect on the incidence of
colon, breast, ovarian, and prostate cancer. It had been speculated that this
latitudinal effect was due in part to sunlight mediated vitamin D synthesis.
However, it was difficult to fully understand how an increase in vitamin D3
synthesis in the skin could relate to cell proliferation and prevention of these
cancers. The reason for this skepticism was that the production of
1,25-dihydroxyvitamin D3 by the kidney was tightly regulated; and therefore, an
increase in the cutaneous production of vitamin D3 would not increase the renal
production of 1,25-dihydroxyvitamin D3, a known inhibitor of proliferation of
various cancer cell lines. Dr. Holick and his colleagues reasoned that maybe
colon, breast, and prostate cells could metabolize 25-hydroxyvitamin D3 to
1,25-dihydroxyvitamin D3 and that this hormone, in turn, would act in an
autocrine/paracrine function to regulate cell growth. Dr. Holick and his
colleagues incubated normal human prostate cells, benign prostatic hypertrophy
cells, and three separate prostate cancer cell lines with 3H-25-hydroxyvitamin
D3. They observed for the first time that normal human prostate cells and human
prostate cancer cells had the synthetic machinery to convert 25-hydroxyvitamin
D3 to 1,25-dihydroxyvitamin D3. This observation provides the basis for a new
concept for the function of vitamin D in tissues not related to calcium
9. Cloning of the Human 25-Hydroxyvitamin D-1α-Hydroxylase and a Novel Use for
Dr. Holick and his colleagues cloned the human vitamin D-1α-hydroxylase with its
entire promoter region. Transfection of this construct into prostate cancer
cells resulted in the expression of the enzyme in the mitochondria of the
prostate cell. Dr. Holick considered another use for his 1α-OHase construct. He
reasoned he could topically apply it to the skin and enhance the production of
1,25(OH)2D3. This could be a unique way to treat psoriasis by gene therapy with
1α-OHase. He topically applied the naked plasmid in water to the skin of mice
and found that there was increased expression of the 1α-OHase throughout the
entire epidermis. This offers a new avenue for using the vitamin D system for
health and disease of the skin.
10. Parathyroid Hormone Related Peptide and the Skin
His laboratory recognized the important role that parathyroid hormone related
peptide (PTHrP) played in regulating skin and hair cell growth. He developed a
formulation for the topical application of peptides that had agonistic or
antagonistic activity of the PTHrP. In a novel group of studies, he demonstrated
that the topical application of a PTHrP agonist markedly inhibited skin cell
growth and the antagonist markedly stimulated skin and hair growth in mice. He
recently completed a study demonstrating the topical application of PTH (1-34)
is safe and efficient for treating psoriasis. He also found that PTHrP receptor
antangonist PTH(7-34) was effective in stimulating hair growth and preventing
chemotherapy induced alopecia. These observations offer a novel approach for
treating hirsutism and male and female pattern baldness.