To sum up, the adherence to the prescribed supplement regiment was good in this target group of women, with critically low 25-OHD levels and very poor muscular performance at baseline. Taken all participants together, the improved grip strength was significantly associated to the number of tablets taken and this was also the case with improved upper leg performance in the target group.
Discussion of results
This was a real life study in a multicultural primary care made in cooperation with the antenatal care. We targeted women at special risk for complications due to severe vitamin D deficiency. Path ological bone turn-over at baseline was significantly reduced already after a few months.
Like most Western countries, Sweden as a country has an influx of refugees from the global conflict regions thus changing the ill-health patterns in the population and brings up a need for new clinical practices [
12,
13]. Non-adherence to medication and advice can be due to lack of cultural competence from a care-giver perspective leading to that clinical needs are missed [
14] such as the deficient levels of vitamin D (25-OHD) in pregnant non-Western women living in Europe [
15‐
17], in adolescent girls in England [
18], and in post-partum mothers [
15]. Lack of vitamin D also occurs in high frequency in native populations of women in Beijing [
19] and Denmark [
20] while Swedish women in general practice seldom have levels below 25 nmol/L [
21]. Notably, no clinical data were provided in any of the above mentioned studies.
A standard estimate of appropriate serum 25-OHD is 50 nmol/L [
6,
8,
22,
23]. Our TG women had much lower values and even immeasurable 25-OHD (i.e., <10 nmol/L) levels and also very weak hands and legs. With supplementation, their 25-OHD levels increased to 50 nmol/L 25-OHD which apparently had contributed to improve their grip strength 25% on the average. Yet, their mean grip strength value was only 188 N, which still was 80 N below the “normal” mean value for healthy Swedish women (268 N for 20–29 years) [
11]. Also, a quarter of the TG women could not stand on one leg at any time. This finding is unclear and worthy of further investigation, as are the other possible explanations for weak handiness. One fifth of the TG women had a positive Trendelenburg’s test at baseline, compared with only a few at Time II not possible to relate directly to tablet intake probably due to small number of persons.
Long recognised as important for bone health, vitamin D has attracted interest also for its possible non-skeletal benefits. Whether supplemental vitamin D lowers and at what dose is required to reduce health hazards is uncertain [
24]. More is not necessary better, as shown here when a moderate dose of 800 or 1600 IU vitamin D3 was beneficial also for women with very poor status. In a multicultural clinical trial like this it is impossible to correct for all confounders. Here we previously have accounted for many likely confounders but only physical activity was found relevant.
Grip strength is a measure of upper extremity function commonly used as a general indicator of frailty among older adults. Here, improved grip strength and ability to squat correlated to the number of tablets consumed rather than the laboratory levels of 25-OHD, and so likely indicating the importance of calcium content when it comes to improving skeletal muscle function.
The cut-off points for S-25-OHD were from the laboratory [
10]. Our laboratory consistently returned values 10–20% lower than the precise LC-MS reference methods used at other laboratories [
25].
Some authors have suggested 75 nmol/L of 25-OHD as optimal for soft tissue health [
10,
22,
26,
27]. Our RG women with better baseline values (25–50 nmol/L 25-OHD) also increased their 25-OHD levels significantly and increased their grip strength from subnormal levels (mean 257 N) to the normal mean value for 30–39-year-old Swedish women [
11].
Clinically, both appearance and gait among the TG women had improved by Time I. Here, we assessed physical performance as separate tests and not a summary score that sometimes is used to illustrate a broad measure of physical performance [
27]. We considered separate measures of performance easier to manage in a multicultural clinical practice.
Gestational age and breastfeeding indicating also oestrogen status may theoretically influence performance of physical tests but no such relation was found here, nor in our previous study [
1].
The association between serum vitamin D, supplemental vitamin D and physical performance is still poorly understood. Our low correlation values between 25-OHD and improved grip strength could be partly explained by the conservative replacing method for immeasurable 25-OHD values and/or a total body calcium deficiency. Participants also reported an increase in their physical activity but this could not be used to explain their improved test results.
Strengths and limitations
This study is by us considered to have a good ecological validity. A problem we faced was the difficulty of enrolling pregnant and recent mothers. Language and cultural differences were additional barriers, but in spite of this most of the TG women enrolled when the Somali assistant nurses contacted them.
To note, the dropout rate was higher among the more affluent reference women than among the marginalized target group women. This may have distorted some of the results, which must in any case be interpreted with caution due to the small sample size from a single site.
Our results cannot be generalized but should be possible to transfer to similar patient settings as here, and they might also be relevant for individuals with low UV exposure for prolonged periods.
Regrettably, a randomized controlled intervention study was not possible to perform due to ethical concerns. Instead, we performed this in situ study in a single setting with a limited number of participants at risk.
Comparison with other studies
Hypovitaminosis D can jeopardize development of the foetus and cause neonate hypocalcaemia, which motivated us to focus on pregnant women in our study [
10]. Many studies conclude that vitamin D deficiency is common in middle Eastern female immigrants but that their response to prescribed vitamin D dosages is often inadequate [
28].
This real life study included persons with minimal UV-exposure during an extended time. Here, the estimated level increase of 25-OHD was 31 nmol/L per 800 IU (20 ug) vitamin D3 plus 500 mg calcium in the TG and even 41 nmol/L in RG compared to a lower increase of 25 nmol/L at intake of 1000 IU according to previous literature [
29]. The comparatively higher result in RG could be due to more UV-exposure but this needs further investigation. Our results may provide a formula for calculating the amount of supplemental intake in pregnancy during long-term to increase 25-OHD levels to normal in similar groups of persons with low UV-exposure.
Cutaneous synthesis of vitamin D3 decreases with age inducing interest in the vitamin D status and lower extremity functioning of older adults [
8] but the relationship between muscle strength and supplemental vitamin D has been discrepant with regard to muscle strength and function [
30].
Cross-sectional studies have shown a positive relationship between muscle strength, performance and 25-OHD levels among postmenopausal women having levels below 60 nmol/L and in hip-fracture patients [
31,
32]. In women 19–29 years with <50 nmol/L 25-OHD, more physical activity was associated with both good grip strength and higher serum 25-OHD [
22].
Intervention studies have provided diverging results depending on the study population and intervention methods. On the positive side are studies of older adults [
8] and athletes with sub-optimal 25-OHD [
22] in whom supplemental vitamin D with calcium improved muscle strength and athletic performance. An important point here is that a combination of calcium and vitamin D was found to be superior for improving muscle function compared with calcium alone [
33]. In a young adult sample, Danish investigators found improved quadriceps muscle power after vitamin D treatment in veiled Arabic adult women [
7]. On contrary, a Norwegian study of non-Western adults, many of whom were from Somalia, found that men and women with on average 25-OHD of 27 nmol/L did not benefit from 4 months of supplemental vitamin D, notably without calcium, as measured by their power to jump, grip, or rise from a chair [
34]. Furthermore, a study of young women found no relationship between increased 25-OHD and improved muscle strength after having received vitamin D and calcium [
35]. However, small beneficial effects of supplemental vitamin D on balance, gait or sit-to-stand performance were found in community-dwelling older women [
36].
Adherence studies of supplemental vitamin D intake are few.
Clinical significance
In clinical practice, signs such as a weak handgrip, the inability to squat or a waddling gait (also called Trendelenburg gait) indicate a severe vitamin D deficiency in high-risk groups.
Giving supplements containing vitamin D and calcium may help improve function and seem to be well accepted, but support from native-speaking assistants might be needed to improve adherence. Repeated measurements of 25-OHD appear to be of little use and might be replaced by tablet intake estimation and simple physical performance tests.
Future studies
Our findings warrant further investigation, including studies focusing on methods to improve adherence to supplemental prescriptions where also costs of supplements, attitudes and behaviour-related socio-cultural factors should be explored by e.g., using qualitative research methods. Future studies could also focus on delivery outcome, efficacy in daily infant care, balance and osteomalacia.