There has been very little prior research on the effects of vitamin D3 and omega-3 fatty acids on levels of serum oestradiol (E2, an oestrogen steroid hormone and the major female sex hormone, which helps to regulate menstrual reproductive cycles), especially in pre-menopausal women diagnosed with vitamin D deficiency.
As such, researchers at Jordan's Applied Science Private University and Fakeeh College for Medical Sciences conducted an RCT to evaluate the impact of daily individual supplementation with vitamin D3 and omega-3, as well as combined supplementation of the two, on E2 levels in vitamin D-deficient pre-menopausal Jordanian women.
Conflicts and combined effects
They recruited a total of 86 subjects, aged 32.8 to 41.7 years old, and divided them into four groups: a control group that received no supplementation, a vitamin D3 group (each subject administered 50,000 IU of vitamin D3 once a week), an omega-3 group (each subject administered 1,000 mg of wild salmon and fish oil complex containing 300mg of omega-3 once a day), and a combined supplementation group (each subject administered 50,000 IU of vitamin D3 once a week, plus 1,000 mg of wild salmon and fish oil complex containing 300 mg of omega-3 once a day).
The study lasted for eight weeks, during which fasting serum levels for 25-hydroxy vitamin D (25OHD) and E2 were assessed at baseline and at the end of the trial, and mid-follicular serum levels of 25OHD and E2 were assessed at the end of the trial.
The researchers then reported that within the vitamin D3 group, they observed a significant increase of up to 21.9ng/ml in serum 25OHD levels, and a significant decrease of up to 41.9ng/ml in serum E2 levels.
In the omega-3 group, there was a significant decrease of up to 20.4ng/ml in serum 25OHD levels, and a significant increase of up to 45.8ng/ml in serum E2 levels. When it came to the combined supplementation group, the researchers observed a significant increase in serum levels of both 25OHD (up to 32.6ng/ml) and E2 (up to 45.8ng/ml).
They wrote that taken together, vitamin D3 and omega-3 supplementation managed to nullify each other's reduction of E2 and 25OHD, respectively. They added that this meant that the combination of vitamin D3 and omega-3 presented several health benefits, including lowered risk of kidney, bone and cardiovascular diseases.
The researchers explained that vitamin D deficiency was a "known risk factor" for heart disease, especially in chronic kidney disease patients. As vitamin D is "hydroxylated to 25OHD and then converted to the active form, 1,25(OH)2 D in the kidney by 1α-hydroxylase", this may be suppressed by decreased renal function and therefore, result in lower 1,25(OH)2 D levels in chronic kidney disease patients.
As such, they deemed it necessary to replenish 1,25(OH)2 D levels in such patients, in order to lower their cardiovascular disease risk. One way to achieve this is through omega-3 supplementation.
They referred to an earlier study on eight chronic kidney disease patients with 25OHD insufficiency or deficiency, who were undergoing haemodialysis. The study found that while co-supplementation of 2,000mg of omega-3 and vitamin D3 over the course of three months had led to a statistically insignificant increase in 1,25(OH)2 D levels, it also had resulted in a statistically significant increase in 25OHD levels.
They added that they did not measure the serum levels of omega-3 fatty acids and 1,25(OH)2 D in the subjects, which could be considered a limitation.
However, a possible strength was the administration of omega-3 to a significant number of vitamin D-deficient — but otherwise healthy — women, which led to higher E2 levels and could therefore be "beneficial for (the) treatment of osteoporosis in postmenopausal females".
In conclusion, they wrote: "To the best of our knowledge, this study is the first to show the effect of the vitamin D plus omega-3 fatty acid group combination on E2 in normal young pre-menopausal females with vitamin D deficiency.
"The vitamin D plus omega-3 fatty acid group reversed the decreasing effect of vitamin D3 alone and omega-3 alone on E2 and 25OHD, respectively. The vitamin D plus omega-3 fatty acid group showed a significant increase in both 25OHD and E2 levels without causing disturbances in PTH (parathyroid hormone), calcium and phosphate homeostasis, or any kidney or liver toxicity.
"Based on these findings, it seems that the positive effect of omega-3 fatty acids alone on E2 is not through the suppression of 25OHD, because in its combination with vitamin D3, an increase in both 25OHD and E2 occurred.
"Using vitamin D plus omega-3 fatty acids can be beneficial for several diseases, including — but not limited to — the improvement of bone-related diseases and cardiovascular diseases, especially chronic kidney disease. Certainly, further research is required to explore and confirm the beneficial effects of this combination."
Source: Clinical Pharmacology: Advances and Applications
"Assessing the effect of omega-3 fatty acid combined with vitamin D3 versus vitamin D3 alone on estradiol levels: a randomized, placebo-controlled trial in females with vitamin D deficiency"
Authors: Amani H Al-Shaer, et al.