Vitamin D may help protect against liver damage in those with PBC: Study
D3 shown to inhibit inflammatory pathways, may be new treatment strategy
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Vitamin D was shown to ease the effects of liver inflammation and damage in primary biliary cholangitis (PBC), a chronic form of cholangitis, in a new study, suggesting that supplements with D3 — the vitamin type linked to sunlight and some foods — may offer potential therapeutic benefit to people with this liver disease.
The researchers found that treatment with vitamin D was able to prevent a type of immune cells known as proinflammatory immune macrophages from entering the liver and releasing inflammatory molecules. Patients given supplements had lower levels of several biomarkers that can indicate liver damage.
According to the scientists, these findings shed new light on the exact immune-mediating properties of vitamin D3 in PBC, and suggest supplements may be a new treatment option.
“This study provides novel insights into the immunomodulatory effects of [vitamin D3] in PBC and highlights its potential therapeutic implications,” the researchers wrote.
The study, “Vitamin D3 attenuates hepatic inflammation in primary biliary cholangitis by inhibiting TLR4/NF-κB mediated M1 macrophage polarization,” was published in the journal Scientific Reports.
Cholangitis is a liver condition marked by inflammation of the bile ducts, the tubes that transport the digestive fluid bile from the liver to the intestines. Bile duct inflammation obstructs bile flow, causing the fluid to accumulate in the liver and ultimately leading to liver damage.
People with PBC have an autoimmune liver condition that causes cholangitis in the bile ducts within the liver.
Macrophages, immune cells that normally help fight infections, are known to play a role in bile duct inflammation in PBC. These cells can polarize, or mature, into two main types: M1 macrophages, which promote an inflammatory response, and M2 macrophages, which facilitate tissue repair and help resolve inflammation.
Examining supplement use alongside UDCA treatment
Mostly known for its role in calcium metabolism, and for promoting bone health, vitamin D is a fat-soluble nutrient. But this vitamin can also exert immunomodulatory effects, including the regulation of macrophage activation and function.
Data from a small clinical trial suggested that adding vitamin D to the first-line PBC treatment ursodeoxycholic acid (UDCA, marketed as Urso and Actigall, with generics also available) is superior to UDCA alone at reducing liver damage and liver scarring, and easing symptoms, in patients.
“However, it remains unclear whether macrophage polarization in the liver of PBC patients is regulated by [vitamin D3],” the researchers wrote.
To address this gap, a team in China investigated the relationship between vitamin D levels and macrophage polarization in PBC. The scientists used clinical data from PBC patients, a PBC mouse model, and cell cultures.
The team first confirmed the significant infiltration of M1 macrophages, but not M2 macrophages, in the livers of PBC patients, using both gene activity data and patient samples.
Next, the researchers examined samples from 73 PBC patients who had been followed at their hospital. All received UDCA treatment, and 44 also received calcitriol, the active form of vitamin D. A total of 40 healthy volunteers were also included as controls.
Blood levels of vitamin D were significantly lower in PBC patients than in healthy controls. Still, the levels were higher in calcitriol-treated PBC patients than in untreated patients, the data showed.
Calcitriol treatment also significantly lowered levels of several biomarkers indicative of liver damage and reduced inflammatory cell infiltration into the liver, predominantly surrounding the small bile ducts, the researchers noted.
Vitamin D also shown to reduce liver biomarker levels in mice
The team then examined mice with induced PBC, which exhibited significantly elevated blood levels of several liver injury biomarkers and a large number of inflammatory cells in the liver.
As in patients, vitamin D treatment reduced liver biomarker levels and inflammatory cell infiltration.
Looking more closely, vitamin D was shown to significantly reduce the infiltration of M1 macrophages and to suppress the production of MCP-1, a signaling protein released by inflammatory macrophages that recruits other inflammatory cells. Several other proinflammatory proteins — specifically TNF-alpha, interleukin-1-beta, and interleukin-6 — were also reduced in response to vitamin D.
Lastly, experiments demonstrated that vitamin D suppressed the polarization of M1 macrophages in PBC livers by inhibiting a signaling pathway known as TLR4/NF-kappaB. These findings were confirmed using cell-based tests.
These findings provide novel insights into the immunomodulatory properties of [vitamin D] in PBC, and may offer a theoretical foundation for the development of therapeutic strategies to decelerate disease progression.
“This study has revealed for the first time that [vitamin D] can ameliorate the progression of PBC through modulation of [liver] macrophage polarization,” the researchers concluded.
The team added that “these findings provide novel insights into the immunomodulatory properties of [vitamin D] in PBC.” Further, this study “may offer a theoretical foundation for the development of therapeutic strategies to decelerate disease progression through [vitamin D]-mediated macrophage polarization,” the scientists wrote.
