Skip to main content
NCBI home page
Therapeutic Advances in Endocrinology and Metabolism logoLink to Therapeutic Advances in Endocrinology and Metabolism
. 2015 Aug;6(4):149–154. doi: 10.1177/2042018815578998

The effects of intermittent vitamin D3 supplementation on muscle strength and metabolic parameters in postmenopausal women with type 2 diabetes: a randomized controlled study

Roseane Cavalcante 1, Juliana Maia 1, Patrícia Mesquita 2,✉, Rafael Henrique 3, Luiz Griz 4, Maria P Bandeira 4, Francisco Bandeira 4
PMCID: PMC4525124  PMID: 26301064

Abstract

Background:

The aim of this study was to evaluate the effect of weekly vitamin D3 supplementation on metabolic parameters and muscle strength of postmenopausal women with type 2 diabetes.

Methods:

A total of 38 patients with serum 25-hydroxy vitamin D [25(OH)D] below 30 ng/ml and hand strength below 20 kg were randomly assigned to oral vitamin D3 (6600 IU/week in 2 cc oil preparation) or 2 cc olive oil weekly for 3 months.

Results:

There were nonsignificant increases in serum 25(OH)D in the intervention group to 22.98 ± 4.23 ng/ml and nonsignificant decreases in the control group to 22.84 ± 3.88 (26% of the intervention and 48% of the control groups had 25(OH)D < 20 ng/ml). Handgrip strength improved significantly in the intervention group (right arm 17.4 ± 2.68 to 19.9 ± 3.53 kg, p = 0.002; left arm 16.31 ± 2.6 to 18.46 ± 3.2 kg, p < 0.001) but not in the control group (right arm 16.87 ± 3.99 to 17.93 ± 4.91 kg, p = 0.1; left arm 16.13 ± 4.29 to 16.86 ± 4.79 kg, p < 0.2). More patients in the control group became obese at the end of the study period (p = 0.014). There were no significant changes in mean fasting glucose, glycated haemoglobin (HbA1c), serum triglycerides and blood pressure with vitamin D supplementation. Systolic blood pressure increased significantly in the control group from 136.6 ± 18.6 to 141.4 ± 17.6 mmHg, p = 0.04).

Conclusions:

Vitamin D3 supplementation in doses equivalent to 942 IU/day improved isometric handgrip strength, but had no effect on glycaemic control in postmenopausal women with longstanding type 2 diabetes.

Keywords: cholecalciferol, diabetes mellitus, dietary supplementation, type 2, vitamin D

Introduction

Type 2 diabetes mellitus (DM2) and hypovitaminosis D are global epidemics and are considered public health problems because of the implications in the development of various complications [Bandeira et al. 2006; Viegas et al. 2011]. Both conditions are risk factors for bone loss, causing damage to bone mineral metabolism in an insidious and asymptomatic way, and with higher incidence in postmenopausal women [Viegas et al. 2011].

Clinical and epidemiological evidence suggest an association between vitamin D deficiency and the development and metabolic control of DM2, since this can affect insulin sensitivity and response [Knekt et al. 2008]. Sarcopenia is characterized by a progressive decline in muscle mass which occurs as a consequence of the ageing process, but may be aggravated by associated factors such as vitamin D deficiency and longstanding diabetes [Ross et al. 2010]. It is unclear, however, whether there is a causal relationship between these conditions, which concentrations of serum 25-hydroxy vitamin D ( 25(OH)D) better correlate with them or whether supplementation of vitamin D would have a positive impact on the metabolic control and muscle strength of DM2 [Cruz-Jentoft et al. 2010].

Methods

A total of 38 postmenopausal type 2 diabetic women were recruited from outpatient clinic consecutively with serum 25(OH)D < 30 ng/ml and hand strength below 20 kg were randomly assigned to oral vitamin D3 (6600 IU, equivalent to 943 IU per day, in 2 cc oil preparation) or 2cc olive oil weekly for 3 months with the study medication being administered under supervision in all subjects. Vitamin dose was selected based on recommendation of the Institute of Medicine [Ross et al. 2010].

Exclusion criteria were as follows: patients with type 1 diabetes; use of medications known to interfere with bone metabolism such as bisphosphonates, hormonal therapy, anabolic steroids, calcium and vitamin D supplementations and glucocorticoids; primary hyperparathyroidism, uncontrolled hyper and hypothyroidism, Paget’s disease of bone; malignant disease; chronic kidney and liver disease; severe vitamin D deficiency (serum 25(OH)D < 15 ng/ml); neurological disease with impairment in muscle function such as dementia, Parkinson’s disease and multiple sclerosis; rheumatoid arthritis; congestive heart failure; HIV infection; and malabsorption syndromes.

Randomization was performed by the statistical program research randomizer. The intervention group received vitamin D3 (AdderaD3, Farmasa Laboratories, Sao Paulo, Brazil) in extra virgin olive oil and the control group received natural extra virgin olive oil, the same olive oil given to the group intervention. Administration of the dose of the control and intervention group happened weekly, supervised, for 12 consecutive weeks. The intervention dose of vitamin D3 was in agreement with European and American recommendations, which corresponds to 6600 IU weekly or 942 IU daily [Ross et al. 2010].

Handgrip strength was assessed before and after the intervention using the dynamometer technique, (JAMAR dynamometer; Lafayette Instrument Company, IN, USA). Serum 25(OH)D concentrations were measured by chemiluminometric assay (LIAISON, DiaSorin, USA). Assay sensitivity, defined as the lowest value different from zero, was 1.8 ng/ml and the interassay coefficient of variation was 5%. Serum glucose, triglycerides, creatinine, glycated haemoglobin (HbA1c), total cholesterol and fractions, and calcium were measured using an autoanalyser (Johnson & Johnson, USA). The study was approved by the Ethics Research Committee of Agamenon Magalhaes Hospital, under registration CAAE: 0235.0.236.000-10.

Statistical analysis

For continuous variables, Student’s t-test was used for independent samples or the Mann–Whitney test to compare the groups in each assessment and the paired Student’s t-test or Wilcoxon test for paired data to compare two assessments in each group. To compare more than two assessments in each group, the F test (analysis of variance) was used for repeated measures with multiple comparisons of Bonferroni. Student’s t-tests for independent samples and paired Student’s t-test were used in case of the verification of the hypothesis of normal distribution.

The chi-squared, or Exact, test was used to assess categorical variables between groups and all statistical analysis were performed using the SPSS program (version 17). The results of the categorical variables were expressed as percentages and numerical variables as means and standard deviations. p values < 0.05 for hypotheses of bilateral tests indicated a significant difference.

Results

Baseline characteristics in the intervention and control groups were: age 62.16 ± 7.62 versus 62.32 ± 8.00 years; p = 0.9, diabetes duration 11.1 ± 7.4 versus 8.95 ± 7.4 years; p = 0.36, BMI 27.6 ± 5.3 versus 28.2 ±5.9 kg/m2; p = 0.6, HbA1c 8.18 ± 2.13 versus 9.13 ± 2.12 %; p = 0.15, serum 25(OH)D 22.24 ± 3.98 versus 22.91 ± 4.21 ng/ml, p = 0.6), serum total cholesterol 212.16 ± 47.57 versus 198.68 ± 35.45 mg/dl; p = 0.38, serum triglycerides 175.68 ± 86.59 versus 191.42 ± 124.66 mg/dl; p = 0.96, serum high-density lipoprotein cholesterol (HDL-C) 51.26 ± 11.66 versus 50.58 ± 13.82 mg/dl; p = 0.87 (Table 1).

Table 1.

Baseline characteristics of study subjects.

Variable Intervention Control p value
Age (years) 62.16 ± 7.62 62.32 ± 8.00 0.95
Duration of diabetes (years) 11.16 ± 7.46 8.95 ± 7.40 0.36
BMI (kg/m2) 27.6 ± 5.3 28.2 ± 5.9 0.61
SBP (mm Hg) 136.32 ± 12.78 136 ± 12.46 0.65
DBP (mm Hg) 81.32 ± 7.42 84.47 ± 8.48 0.23
25(OH)D (ng/ml) 22.4 ± 3.98 22.91 ± 4.21 0.62
RAHS (kg) 17.40 ± 2.68 16.87 ± 3.99 0.63
LAHS (kg) 16.31 ± 2.60 16.13 ± 4.29 0.87
HbA1c (%) 8.18 ± 2.13 9.13 ± 2.12 0.15
Total cholesterol (mg/dl) 212.16 ± 47.57 198.68 ± 35.45 0.38
HDL-C (mg/dl) 51.26 ± 11.66 50.58 ± 13.82 0.87
LDL-C (mg/dl) 130.58 ± 46.02 112.72 ± 41.29 0.23
Triglycerides (mg/dl) 175.68 ± 86.59 191.42 ± 124.86 0.98
Open in a new tab

25(OH)D: serum 25-hydroxy vitamin D; BMI: body mass index; DBP: diastolic blood pressure; HDL-C: high-density lipoprotein cholesterol; LAHS: left arm handgrip strength; LDL-C: low-density lipoprotein cholesterol; RAHS: right arm handgrip strength; SBP: systolic blood pressure.

At the end of treatment period, there were nonsignificant increases in serum 25(OH)D in the intervention group to 22.98 ± 4.23 ng/ml and nonsignificant decreases in the control group to 22.84 ± 3.88 (26% of the intervention and 48% of the control groups had 25(OH)D < 20 ng/ml). Handgrip strength improved significantly in the intervention group [right arm 17.4 ± 2.68 to 19.9 ± 3.53 kg, p = 0.002 (Figure 1); left arm 16.31 ± 2.6 to 18.46 ± 3.2 kg, p < 0.001 (Figure 2)], but not in the control group [right arm 16.87 ± 3.99 to 17.93 ± 4.91 kg, p = 0.1 (Figure 1); left arm 16.13 ± 4.29 to 16.86 ± 4.79 kg, p < 0.2 (Figure 2)].

Figure 1.

Figure 1.

Open in a new tab

Handgrip strength in the right arm before and after vitamin D supplementation.

Figure 2.

Figure 2.

Open in a new tab

Handgrip strength in the left arm before and after vitamin D supplementation.

There were no significant differences in the distribution of body mass index (BMI) at baseline, but more patients in the control group became obese at the end of the study period (p = 0.014). There were no significant changes in mean fasting plasma glucose (FPG) (155.5 ± 67.4 to 163.4 ± 87.9 mg/dl, p = 0.7), postprandial glucose (PPG) 213.5 ± 87.7 to 210.7 68.8 mg/dl, p = 0.8), HbA1c (8.18 ± 2.13 to 8.67 ± 2.41 %, p = 0.1), serum triglycerides (175.68 ± 86.5 to 169.63 ± 62.17 mg/dl, p = 0.9), systolic blood pressure (SBP) (136.3 ± 12.7 to 139.42 ± 4.2 mmHg, p = 0.4) and diastolic blood pressure (DBP) (81.3 ± 7.4 to 83.0 ± 10.0 mmHg, p = 0.4) with vitamin D supplementation. SBP increased significantly in the control group from 136.6 ± 18.6 to 141.4 ± 17.6 mmHg (p = 0.04).

Discussion

Our study showed a significant improvement in handgrip strength with vitamin D3 supplementation in postmenopausal women with T2DM but no effect on blood glucose control, considering an exposed dose equivalent to 943 IU a day. Our patients were well matched for clinical and biochemical parameters, and there were no hand joints abnormalities in both groups. In agreement with our findings, other authors have not demonstrated improvement in glycaemic parameters with vitamin D supplementation. Jorde and Figenschau, evaluating the supplementation of 40,000 IU of cholecalciferol weekly versus placebo for 6 months, showed no reduction in HbA1c in subjects with DM2 or improvement in insulin secretion [Jorde and Figenschau, 2009]. Mitri and colleagues, however, evaluated through a randomized clinical trial, the effect of supplementation with 800 mg of calcium and 2000 IU of cholecalciferol per day alone or in combination on pancreatic β-cell function, insulin sensitivity and glucose tolerance in adults with a high-risk of developing DM2, showing no significant effect [Mitri et al. 2011]. In this respect, another study on new-onset type 1 diabetic patients showed no improvement in blood glucose control with 2000 IU cholecalciferol daily, but there was a less progressive decline in serum C-peptide concentration in an 18-month period [Gabbay et al. 2012].

In the present study there was also no improvement in lipid profile with vitamin D3 supplementation. A study involving 1259 postmenopausal women, comparing daily dose of 1 g of calcium and 400 IU of vitamin D3 with placebo, in a 5-year period, found no significant changes in serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol and triglycerides levels [Rajpathak et al. 2010]. However, our results demonstrated a beneficial effect of vitamin D on handgrip strength during the intervention period.

Some studies have evaluated the relationship between diabetes mellitus and handgrip strength, which proved to be reduced in diabetic patients. In a study by Cetinus and colleagues, 76 patients with DM2, handgrip strength using the Jamar dynamometer showed significantly lower values compared with the control group [Cetinus et al. 2005]. Savas and colleagues measured the handgrip strength in 44 patients with DM2 with a mean age of 60 years, and showed that both handgrip and pinch strength were lower in diabetic patients than in nondiabetic patients in both hands [Savas et al. 2007]. In another study in 70 female geriatric patients above 65 years of age, although baseline serum 25(OH)D concentrations were significantly associated with knee extension strength, handgrip strength and leg extension power, 400 IU of cholecalciferol plus 500 mg calcium supplementation daily compared with placebo plus calcium did not result in significant differences in strength or functional mobility during a period of 6 months [Janssen et al. 2010].

Our study differs in that it was performed in diabetic female patients and the dose used was much higher. In a study on young healthy females high dose vitamin D3 supplementation (60,000 IU/week for 8 weeks followed by 60,000 IU twice a month for 4 months) did not improve handgrip strength or quality of life [Goswami et al. 2012]. In another study in 30 nondiabetic adult patients, 2 dose schedules of cholecalciferol were compared and positive effects on muscle strength were found with both 2000 IU and 5000 IU daily for 3 months [Diamond et al. 2013]. In this respect, longer intervals of administration of vitamin D3 doses may not be functionally effective [Glendenning et al. 2012].

Although we cannot exclude the influence of weight gain on blood pressure in the control group, different recent scientific evidence indicates an inverse relationship between vitamin D and blood pressure. Forman and colleagues found that plasma 25(OH)D levels were inversely associated with the risk of hypertension [Forman et al. 2007]. Analysis results of three large prospective cohort studies showed no association between high intake of vitamin D and increasing the risk of incident of arterial hypertension [Forman et al. 2005]. Almirall and colleagues, analysing the prevalence of hypovitaminosis D in a cross-sectional study with 237 subjects, most of whom being women over 64 years of age, observed a large negative association between serum 25(OH)D and SBP and DBP [Almirall et al. 2010].

In the present study, although there were no significant changes in SBP with vitamin D3 supplementation, there were significant increases in the control group. In this respect, a recent study, from Denmark, found that at least in patients with vitamin D deficiency (serum 25(OH)D < 32 ng/ml) there was a significant reduction in 24-hour ambulatory blood pressure as well as in central blood pressure estimated by applanation tonometry with vitamin D supplementation [Larsen et al. 2012]. Overall there were nonsignificant reductions in 24-hour measurements. Baseline mean serum 25(OH)D concentrations were similar to what we found in our study (23 ng/ml), but the cholecalciferol dose was higher (3000 IU/day) and treatment duration was longer (5 months). Another study, from Boston, used different doses of cholecalciferol for 3 months in hypertensive blacks and found no significant changes in DBP. The changes in SBP were -0.66 mm Hg for 1000 IU/day, -3.4 mm Hg for 2000 IU/day and -4 mm Hg for 4000 IU/day [Forman et al. 2013].

The present study found nonsignificant increases in serum 25(OH)D in the intervention group and nonsignificant decreases in the control group (26% of the intervention and 48% of the control groups had 25(OH)D < 20 ng/ml) at the end of treatment period. This is in line with other already published studies, which show that diabetic patients may have a satisfactory clinical response without an effective laboratory response increased in 25(OH)D with vitamin D3 supplementation [Sugden et al. 2008]. But although our patients had a low dietary vitamin D intake, they did not present with very low serum 25(OH)D levels (22.2 ng/ml) due to a regular Sun exposure. This may also explain why the supplementation dose used did not lead to significant increases in serum 25(OH)D. This could be achieved possible with a higher supplementation dose.

In conclusion, vitamin D3 supplementation in doses equivalent to 942 IU/day improved isometric handgrip strength, but had no effect on glycaemic control in postmenopausal women with longstanding DM2.

Footnotes

Declaration of Conflicting Interests: The authors declare no conflicts of interest in preparing this article.

Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

References

  1. Almirall J., Vaqueiro M., Bar M., Anton E. (2010) Association of low serum 25-hydroxyvitamin D levels and high arterial blood pressure in the elderly. Nephrol Dial Transplant 25: 503–509. [DOI] [PubMed] [Google Scholar]
  2. Bandeira F., Dreyer P., Eufrasino C., Bandeira C., Freese E. (2006) Vitamin D deficiency: a global perspective. Arq Bras Endocrinol Metab 50: 640–646. [DOI] [PubMed] [Google Scholar]
  3. Cetinus E., Buyukbese M., Uzel M., Ekerbicer H., Karaoguz A. (2005) Hand grip strength in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 70: 278–286. [DOI] [PubMed] [Google Scholar]
  4. Cruz-Jentoft A., Baeyens J., Bauer J., Boirie Y., Cederholm T., Landi F., et al. (2010) Sarcopenia: European consensus on definition and diagnosis. Age Ageing 39: 412–423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Diamond T., Wong Y., Golombick T. (2013) Effect of oral cholecalciferol 2,000 versus 5,000 on serum vitamin D, PTH, bone and muscle strength in patients with vitamin D deficiency. Osteoporos Int 24: 1101–1105. [DOI] [PubMed] [Google Scholar]
  6. Forman J., Bischoff-Ferrari H., Willett W., Stampfer M., Curhan G. (2005) Vitamin D intake and risk of incidence hypertension: results from three large prospective cohort studies. Hypertension 46: 676–682. [DOI] [PubMed] [Google Scholar]
  7. Forman J., Giovannucci E., Holmes M., Bischoff-Ferrari H., Tworoger S., Willett W., et al. (2007) Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension 49: 1063–1069. [DOI] [PubMed] [Google Scholar]
  8. Forman J., Scott J., Ng K., Drake B., Suarez E., Hayden D., et al. (2013) Effect of vitamin D supplementation on blood pressure in blacks. Hypertension 61: 779–785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gabbay M., Sato M., Finazzo C., Duarte A., Dib S. (2012) Effect of cholecalciferol as adjunctive therapy with insulin on protective immunologic profile and decline of residual β-cell function in new-onset type 1 diabetes mellitus. Arch Ped Adolesc Med 166: 601–607. [DOI] [PubMed] [Google Scholar]
  10. Glendenning P., Zhu K., Inderjeeth C., Howat P., Lewis J., Prince R. (2012) Effects of three-monthly oral 150,000 IU cholecalciferol supplementation on falls, mobility, and muscle strength in older postmenopausal women: a randomized controlled trial. J Bone Miner Res 27: 170–176. [DOI] [PubMed] [Google Scholar]
  11. Goswami R., Vatsa M., Sreenivas V., Singh U., Gupta N., Lakshmy R., et al. (2012) Skeletal muscle strength in Young asian Indian females after vitamin D and calcium supplementation: a double-blind randomized controlled clinical Trial. J Clin Endocrinol Metab 97: 4709–4716. [DOI] [PubMed] [Google Scholar]
  12. Janssen H., Samson M., Verhaar H. (2010) Muscle strength and mobility in vitamin D-insufficient female geriatric patients: a randomized controlled trial on vitamin D and calcium supplementation. Aging Clin Exp Res 22: 78–84. [DOI] [PubMed] [Google Scholar]
  13. Jorde R., Figenschau Y. (2009) Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels. Eur J Nutr 48: 349–354. [DOI] [PubMed] [Google Scholar]
  14. Knekt P., Laaksonen M., Mattila C., Härkänen T., Marniemi J., Heliövaara M., et al. (2008) Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology 19: 666–671. [DOI] [PubMed] [Google Scholar]
  15. Larsen T., Mose F., Bech J., Hansen A., Pedersen E. (2012) Effect of cholecalciferol supplementation during the winter months in patients with hypertension: a randomized placebo-controlled trial. Am J Hypertens 25: 1215–1222. [DOI] [PubMed] [Google Scholar]
  16. Mitri J., Dawson-Hughes B., Hu B., Pittas A. (2011) Effects of vitamin d and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the calcium and vitamin D for diabetes mellitus (CaDDM) randomized controlled trial. Am J Clin Nutr 94: 486–494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rajpathak S., Xue X., Wassertheil-Smoller S., Horn L., Robinson J., Liu S., et al. (2010) Effect of 5 y of calcium plus vitamin D supplementation on change in circulating lipids: results from the Women’s Health Initiative. Am J Clin Nutr 91: 894–899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ross A., Manson J., Abrams S., Aloia J., Brannon P., Clinton S., et al. (2010) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96: 53–58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Savas S., Köroglu B., Koyuncuoglu H., Uzar E., Celik H., Tamer N. (2007) The effects of the diabetes related soft tissue hand lesions and the reduced hand strength on functional disability of hand in type 2 diabetic patients. Diabetes Res Clin Pract 77:77–83. [DOI] [PubMed] [Google Scholar]
  20. Sugden J., Davies J., Witham M., Morris A., Struthers A. (2008) Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabetes Med 25: 320–325. [DOI] [PubMed] [Google Scholar]
  21. Viegas M., Costa C., Lopes A., Griz L., Medeiro M., Bandeira F. (2011) Prevalence of osteoporosis and vertebral fractures in postmenopausal women with type 2 diabetes mellitus and their relationship with duration of the disease and chronic complications. J Diabetes Complications 25: 216–221. [DOI] [PubMed] [Google Scholar]

Articles from Therapeutic Advances in Endocrinology and Metabolism are provided here courtesy of SAGE Publications

RESOURCES