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Biomedical subjects

Michael F Holick

Publications and source records attributed to Michael F Holick.

At least 19 recordsLinked to original sources
PubMed2007

Vitamin D deficiency in a healthy group of mothers and newborn infants.

Plasma 25-hydroxyvitamin D was measured in 40 healthy, mostly Black, mother-infant pairs. Although a majority of mothers received a daily prenatal multivitamin, vitamin D deficiency (<30 nmol/L), was found in 50% of mothers and 65% of their newborn infants, with a positive correlation between maternal and infant plasma 25-hydroxyvitamin D concentrations. Maternal vitamin D deficiency may represent an important risk factor for the development of rickets in children.

Adult↗
PubMed2006

A topical parathyroid hormone/parathyroid hormone-related peptide receptor antagonist stimulates hair growth in mice.

One of the biggest hurdles in developing peptides for the treatment of hair growth disorders is that there has been no effective method of delivering them topically. Murine hair growth can be stimulated with ip injections of the PTH/PTHrP receptor antagonist, PTH (7-34). We sought to determine whether we could deliver PTH (7-34) topically and achieve stimulation of hair growth. We prepared a topical cream by mixing PTH (7-34) into a liposome vehicle (Novasome A). We applied the cream daily to the backs of 5-wk-old female SKH-1 hairless mice for 1 wk. After the 1 wk of treatment, there was marked stimulation of hair growth in the SKH-1 hairless mice. Relative to controls, mice treated with PTH (7-34) had 216% longer hairs (P < 0.001), 40% more visible hairs (P < 0.001), and 43% more hair follicles stained with 5-bromo-2'-deoxyuridine (P < 0.01). A unique aspect of skin is the possibility to directly target it via topical treatment. Our study is the first to report the hair-stimulating effect of a PTH/PTHrP receptor antagonist topically applied to skin in vivo. Thus, we introduce a novel paradigm to develop topical PTH analogs for treating disorders of hair growth.

Administration, Topical↗
PubMed2006

AMPK regulation of the growth of cultured human keratinocytes.

AMP kinase (AMPK) is a fuel sensing enzyme that responds to cellular energy depletion by increasing processes that generate ATP and inhibiting others that require ATP but are not acutely necessary for survival. In the present study, we examined the relationship between AMPK activation and the growth (proliferation) of cultured human keratinocytes and assessed whether the inhibition of keratinocyte growth by vitamin D involves AMPK activation. In addition, we explored whether the inhibition of keratinocyte proliferation as they approach confluence could be AMPK-related. Keratinocytes were incubated for 12 h with the AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). At concentrations of 10(-4) and 10(-3) M, AICAR inhibited keratinocyte growth by 50% and 95%, respectively, based on measurements of thymidine incorporation into DNA. It also increased AMPK and acetyl CoA carboxylase phosphorylation (P-AMPK and P-ACC) and decreased the concentration of malonyl CoA confirming that AMPK activation had occurred. Incubation with the thiazolidinedione, troglitazone (10(-6) M) caused similar alterations in P-AMPK, P-ACC, and cell growth. In contrast, the well known inhibition of keratinocyte growth by 1,25-dihydroxyvitamin D3 (10(-7) and 10(-6) M) was not associated with changes in P-AMPK or P-ACC. Like most cells, the growth of keratinocytes diminished as they approached confluence. Thus, it was of note that we found a progressive increase in P-AMPK (1.5- to 2-fold, p < 0.05) as keratinocytes grown in control medium went from 25% to 100% confluence. In conclusion, the data are consistent with the hypothesis that activation of AMPK acts as a signal to diminish the proliferation of cultured keratinocytes as they approach confluence. They also suggest that AMPK activators, such as AICAR and troglitazone, inhibit keratinocyte growth and that the inhibition of cell growth by 1,25-dihydroxyvitamin D3 is AMPK-independent.

AMP-Activated Protein Kinases↗
PubMed2006

Low bone density in patients receiving methadone maintenance treatment.

AIM: To examine the frequency and severity of low bone mineral density (BMD) among patients enrolled in a methadone maintenance treatment (MMT) program and to ascertain risk factors for low BMD in this population. DESIGN: Cross-sectional. MEASUREMENTS: Data derived from standardized survey, medical record review, and dual energy X-ray densitometry (DXA). RESULTS: DXA results were below normal in 83% (76/92) of the study sample with T-scores < -2.5 (osteoporosis range) in 35% [32/92] and between -1.0 and -2.5 (osteopenia range) in 48% [44/92]. Risk factors for low BMD were common: tobacco use, 91%; heavy alcohol use, 52%; and HIV infection, 28%. Only 17% (16/92) were on medications that lower the risk of osteoporosis: estrogen (n = 5), testosterone (n = 4), calcium (n = 4), and Vitamin D (n = 2). None of the participants reported a known diagnosis of osteoporosis. In bivariate analyses, significant predictors of low BMD were: male gender (p < 0.001), lower weight (p = 0.009), and heavy alcohol use (p = 0.02). CONCLUSION: More than three quarters of this sample of patients in a MMT program had low BMD. Treatable conditions associated with low BMD were commonplace. Efforts to increase awareness of low BMD in MMT patients should be considered so that effective treatment may be employed to lower future fracture risk.

Adult↗
PubMed2006

Vitamin D: its role in cancer prevention and treatment.

Vitamin D, the sunshine vitamin, has been recognized for almost 100 years as being essential for bone health. Vitamin D provides an adequate amount of calcium and phosphorus for the normal development and mineralization of a healthy skeleton. Vitamin D made in the skin or ingested in the diet, however, is biologically inactive and requires obligate hydroxylations first in the liver to 25-hydroxyvitamin D, and then in the kidney to 1,25-dihydroxyvitamin D. 25-Hydroxyvitamin D is the major circulating form of vitamin D that is the best indicator of vitamin D status. 1,25-dihydroxyvitamin D is the biologically active form of vitamin D. This lipid-soluble hormone interacts with its specific nuclear receptor in the intestine and bone to regulate calcium metabolism. It is now recognized that the vitamin D receptor is also present in most tissues and cells in the body. 1,25-dihydroxyvitamin D, by interacting with its receptor in non-calcemic tissues, is able to elicit a wide variety of biologic responses. 1,25-dihydroxyvitamin D regulates cellular growth and influences the modulation of the immune system. There is compelling epidemiologic observations that suggest that living at higher latitudes is associated with increased risk of many common deadly cancers. Both prospective and retrospective studies help support the concept that it is vitamin D deficiency that is the driving force for increased risk of common cancers in people living at higher latitudes. Most tissues and cells not only have a vitamin D receptor, but also have the ability to make 1,25-dihydroxyvitamin D. It has been suggested that increasing vitamin D intake or sun exposure increases circulating concentrations of 25-hydroxyvitamin D, which in turn, is metabolized to 1,25-dihydroxyvitamin D(3) in prostate, colon, breast, etc. The local cellular production of 1,25-dihydroxyvitamin D acts in an autocrine fashion to regulate cell growth and decrease the risk of the cells becoming malignant. Therefore, measurement of 25-hydroxyvitamin D is important not only to monitor vitamin D status for bone health, but also for cancer prevention.

Biomarkers, Tumor↗
PubMed2006

The role of vitamin D for bone health and fracture prevention.

Vitamin D inadequacy is pandemic in adults. Vitamin D deficiency causes osteopenia, precipitates and exacerbates osteoporosis, causes the painful bone disease osteomalacia, and increases muscle weakness, which worsens the risk of falls and fractures. Vitamin D deficiency can be prevented by sensible sun exposure and adequate supplementation. Monitoring serum 25-hydroxyvitamin D is the only way to determine vitamin D status. Recent recommendations suggest that in the absence of sun exposure, adults should ingest 1000 IU of vitamin D3 per day. The ideal healthy blood level of 25-hydroxyvitamin D should be 30 to 60 ng/mL. Vitamin D intoxication occurs when 25-hydroxyvitamin D levels are greater than 150 ng/mL. Three recent reports suggesting that vitamin D and calcium supplementation does not decrease the risk of fracture will be put into perspective in light of the vast literature supporting increasing vitamin D and calcium intake as an effective method for decreasing risk of vertebral and nonvertebral fractures.

Bone and Bones↗
PubMed2006

Vitamin D deficiency and osteoporosis in rehabilitation inpatients.

OBJECTIVE: To determine vitamin D status and bone mineral density (BMD) in patients admitted to a subacute rehabilitation facility. DESIGN: Cross-sectional cohort study. SETTING: Subacute rehabilitation facility. PARTICIPANTS: Fifty-three community-dwelling patients admitted from June through February 2005. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: BMD, 25-hydroxyvitamin D (25[OH]D), C-telopeptide (CTX), osteocalcin, and dietary milk intake. RESULTS: Prevalence of vitamin D deficiency (25[OH]D <20 ng/mL) was 49.1%, while a total of 83% of patients were either vitamin D deficient or insufficient (25[OH]D <30 ng/mL). The prevalence of osteopenia (T score, <-1) was 52.8%; osteoporosis (T score, <-2.5) was 17.0%. CTX (bone resorption marker) was elevated in 60.4% of patients. Osteocalcin (bone formation marker) was elevated in 13.2% of patients. Measurements of bone resorption and formation positively correlated (R2 = .22) indicating increased bone remodeling. CONCLUSIONS: Vitamin D deficiency and osteopenia and osteoporosis were highly prevalent in patients admitted for rehabilitation. Elevated bone resorption and remodeling were evident. This could be due to vitamin D deficiency that should be corrected before antiresorptive therapy is considered. The study emphasizes the need for vigilance for vitamin D status and BMD testing in patients admitted to rehabilitation facilities.

Bone Density↗
PubMed2006

Comparison of the effects of a new conjugated oral estrogen, estradiol-3beta-glucoside, with oral micronized 17beta-estradiol in postmenopausal women.

The objective of this article is to evaluate the pharmacokinetics of serum estrone and estradiol levels in women who were taking either 17beta-estradiol-3beta-glucoside (E(2)-3beta-glucoside) or 17beta-estradiol (E(2)) daily and to examine the effects of E(2)-3beta-glucoside and E(2) on postmenopausal symptoms, gonadotropins, hepatic metabolism, and coagulation factors. Healthy postmenopausal women on estrogen who had undergone a hysterectomy were recruited. Subjects were randomly assigned to receive equivalent doses of either E(2)-3beta-glucoside or micronized E(2) for 28 days. Pharmacokinetic studies of estrone and estradiol were performed on days 1, 2, 28, and 29. Gonadotropin levels and Kupperman Index (KI) scores were determined at baseline and on treatment day 28. Mean serum estradiol and estrone concentrations in those taking E(2)-3beta-glucoside were comparable with those taking E(2). Mean baseline follicle stimulating hormone (FSH) levels were 84 +/- 27 mIU/mL and 71 +/- 24 mIU/mL in the E(2)-3beta-glucoside and E(2) groups, respectively, with significant decreases (P < 0.01) of 54 +/- 21 mIU/mL and 38 +/-18 mIU/mL, respectively, by treatment day 28. Baseline KI scores in the E(2)-3beta-glucoside group were 10 +/- 6 compared with 5 +/- 4 on treatment day 28, which is equivalent to a 50% reduction in menopausal symptoms (P = 0.003). The change in KI scores in the E(2) group was not statistically significant. Total serum estradiol and estrone levels in women taking E(2)-3beta-glucoside are comparable with those in women taking E(2). E(2)-3beta-glucoside reduces serum gonadotropin levels to the premenopausal range and is effective at reducing postmenopausal symptoms. E(2)-3beta-glucoside is a novel synthetic estrogen that is well tolerated and has promise as a hormone replacement therapy.

Administration, Oral↗
PubMed2006

Resurrection of vitamin D deficiency and rickets.

The epidemic scourge of rickets in the 19th century was caused by vitamin D deficiency due to inadequate sun exposure and resulted in growth retardation, muscle weakness, skeletal deformities, hypocalcemia, tetany, and seizures. The encouragement of sensible sun exposure and the fortification of milk with vitamin D resulted in almost complete eradication of the disease. Vitamin D (where D represents D2 or D3) is biologically inert and metabolized in the liver to 25-hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D that is used to determine vitamin D status. 25(OH)D is activated in the kidneys to 1,25-dihydroxyvitamin D [1,25(OH)2D], which regulates calcium, phosphorus, and bone metabolism. Vitamin D deficiency has again become an epidemic in children, and rickets has become a global health issue. In addition to vitamin D deficiency, calcium deficiency and acquired and inherited disorders of vitamin D, calcium, and phosphorus metabolism cause rickets. This review summarizes the role of vitamin D in the prevention of rickets and its importance in the overall health and welfare of infants and children.

Calcium↗
PubMed2006

High prevalence of vitamin D inadequacy and implications for health.

During the past decade, major advances have been made in vitamin D research that transcend the simple concept that vitamin D is Important for the prevention of rickets in children and has little physiologic relevance for adults. Inadequate vitamin D, in addition to causing rickets, prevents children from attaining their genetically programmed peak bone mass, contributes to and exacerbates osteoporosis in adults, and causes the often painful bone disease osteomalacia. Adequate vitamin D is also important for proper muscle functioning, and controversial evidence suggests it may help prevent type 1 diabetes mellitus, hypertension, and many common cancers. Vitamin D inadequacy has been reported in approximately 36% of otherwise healthy young adults and up to 57% of general medicine inpatients in the United States and in even higher percentages in Europe. Recent epidemiological data document the high prevalence of vitamin D inadequacy among elderly patients and especially among patients with osteoporosis. Factors such as low sunlight exposure, age-related decreases in cutaneous synthesis, and diets low in vitamin D contribute to the high prevalence of vitamin D inadequacy. Vitamin D production from cutaneous synthesis or intake from the few vitamin D-rich or enriched foods typically occurs only intermittently. Supplemental doses of vitamin D and sensible sun exposure could prevent deficiency in most of the general population. The purposes of this article are to examine the prevalence of vitamin D inadequacy and to review the potential implications for skeletal and extraskeletal health.

Adult↗
PubMed2005

The role of vitamin D in cancer prevention.

Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects.

Breast Neoplasms↗
PubMed2005

Vitamin D and prevention of colorectal cancer.

BACKGROUND: Inadequate photosynthesis or oral intake of Vitamin D are associated with high incidence rates of colorectal cancer, but the dose-response relationship has not been adequately studied. METHODS: Dose-response gradients from observational studies of Vitamin D intake and serum 25-hydroxyvitamin D were plotted as trend lines. The point on each linear trend line corresponding to an odds ratio of 0.50 provided the prediagnostic Vitamin D intake or 25-hydroxyvitamin D concentration associated with 50% lower risk compared to <100IU/day Vitamin D or <13ng/ml serum 25-hydroxyvitamin D. Medians of these values were determined. RESULTS: Overall, individuals with >or=1000IU/day oral Vitamin D (p<0.0001) or >or=33ng/ml (82nmol/l) serum 25-hydroxyvitamin D (p<0.01) had 50% lower incidence of colorectal cancer compared to reference values. CONCLUSIONS: Intake of 1000IU/day of Vitamin D, half the safe upper intake established by the National Academy of Sciences, was associated with 50% lower risk. Serum 25-hydroxyvitamin D of 33ng/ml, which is known to be safe, also was associated with 50% lower risk. Prompt public health action is needed to increase intake of Vitamin D(3) to 1000IU/day, and to raise 25-hydroxyvitamin D by encouraging a modest duration of sunlight exposure.

Calcium↗
PubMed2005

Topical thyroid hormone accelerates wound healing in mice.

Although the physiologic role of thyroid hormone in skin is not well understood, mounting evidence suggests that T3 plays an important role in epidermal proliferation. The goal of this project was to evaluate whether the topical application of supraphysiologic doses of T3 could accelerate wound healing. We evaluated mice treated with topical T3 vs. the same mice receiving vehicle alone (Novasome A). Ten-millimeter diameter (79 mm2) dorsal skin wounds were established in all animals, and wounds were remeasured 4 d after injury. All animals were evaluated twice: once with the T3 treatment and once with the vehicle alone. Daily topical application of 150 ng T3 resulted in 58% greater wound closure relative to wounds on the same animals receiving vehicle alone (P < 0.001). Furthermore, we determined that wound healing-associated keratin 6 protein expression in hair follicle keratinocytes increased in a dose-dependent manner in vivo during topical T3 treatment. The data support our previous hypothesis that T3 is necessary for optimal wound healing. Now, we further suggest that topical thyroid hormone may be an inexpensive agent to hasten healing of certain wounds.

Administration, Topical↗
PubMed2005

Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy.

PURPOSE: To evaluate serum 25-hydroxyvitamin D [25(OH)D] concentrations and factors related to vitamin D inadequacy in postmenopausal North American women receiving therapy to treat or prevent osteoporosis. METHODS: Serum 25(OH)D and PTH were obtained in 1536 community-dwelling women between November 2003 and March 2004. Multivariate logistic regression was used to assess risk factors for suboptimal (<30 ng/ml) 25(OH)D. RESULTS: Ninety-two percent of study subjects were Caucasian, with a mean age of 71 yr. Thirty-five percent resided at or above latitude 42 degrees north, and 24% resided less than 35 degrees north. Mean (sd) serum 25(OH)D was 30.4 (13.2) ng/ml: serum 25(OH)D was less than 20 ng/ml in 18%; less than 25 ng/ml in 36%; and less than 30 ng/ml in 52%. Prevalence of suboptimal 25(OH)D was significantly higher in subjects who took less than 400 vs. 400 IU/d or more vitamin D. There was a significant negative correlation between serum PTH concentrations and 25(OH)D. Risk factors related to vitamin D inadequacy included age, race, body mass index, medications known to affect vitamin D metabolism, vitamin D supplementation, exercise, education, and physician counseling regarding vitamin D. CONCLUSIONS: More than half of North American women receiving therapy to treat or prevent osteoporosis have vitamin D inadequacy, underscoring the need for improved physician and public education regarding optimization of vitamin D status in this population.

Accidental Falls↗
PubMed2005

Estimates of optimal vitamin D status.

Vitamin D has captured attention as an important determinant of bone health, but there is no common definition of optimal vitamin D status. Herein, we address the question: What is the optimal circulating level of 25-hydroxyvitamin D [25(OH)D] for the skeleton? The opinions of the authors on the minimum level of serum 25(OH)D that is optimal for fracture prevention varied between 50 and 80 nmol/l. However, for five of the six authors, the minimum desirable 25(OH)D concentration clusters between 70 and 80 nmol/l. The authors recognize that the average older man and woman will need intakes of at least 20 to 25 mcg (800 to 1,000 IU) per day of vitamin D(3 )to reach a serum 25(OH)D level of 75 nmol/l. Based on the available evidence, we believe that if older men and women maintain serum levels of 25(OH)D that are higher than the consensus median threshold of 75 nmol/l, they will be at lower risk of fracture.

Adult↗
PubMed2005

Adolescent girls in Maine are at risk for vitamin D insufficiency.

The objective was to determine the seasonal fluctuations in serum 25-hydroxyvitamin D (25-OHD) in a group of healthy adolescents living in a northern climate. Twenty-three 9- to 11-year-old girls participated in the study from September 2000 to March 2003. Serum 25-OHD and parathyroid hormone levels were measured each September and March. Dietary intake of vitamin D was assessed each summer and winter. Summer-sun exposure was evaluated using reports of time spent outdoors. The mean decrease in serum 25-OHD from September to March was 28%. Vitamin D insufficiency (at least one serum 25-OHD level <50 nmol/L) was observed in 11 of 23 (48%) subjects. Four of 23 subjects (17%) exhibited vitamin D insufficiency in both September and March. Mean parathyroid hormone levels increased 4 pg/mL (15%) from September to March. Vitamin D intakes need to be increased in winter at northern latitudes.

Adolescent↗