Beyond bones: Revisiting the role of vitamin D in chronic liver disease

Table 1 Recommended daily intake of vitamin D by sex and age group, according to current dietary reference values

Group	EAR (IU)	RDA (IU)
Men (year)
19-70	400	600
> 70	400 (10 μg)	800 (20 μg)
Women (year)
19-70	400 (10 μg)	600 (15 μg)
> 70	400 (10 μg)	800 (20 μg)

EAR: Estimated average requirement; RDA: Recommended dietary allowance; IU: International unit.

Table 2 Vitamin D-rich foods ranked by content per 100 g serving

Foods	μg/100 g	IU/100 g
Cod liver oil	250	10000
Raw mackerel	16.1	644
Raw salmon	10.9	436
Canned sardines	4.8	192
Raw trout	3.9	156
Raw tuna	1.7	68
Egg (yolk)	5.5	220
Margarine	3.7	148
Beef liver	1.2	48
Yogurt, skim milk	1.2	48
Low-fat milk	1	40
Cheddar and feta cheese	0.5	20
Butter	0.4	16
Orange juice	1	40
Raw shiitake mushrooms	0.5	20
Soy milk	0.7	28

IU: International unit.

Table 3 Overview of published studies on vitamin D supplementation and its therapeutic impact on hepatic conditions

Ref.	Population	Type of study	Intervention	Outcomes
Mohamed et al[153], 2021	328 patients with SBP (168 control group vs 160 supplementation group), aged over 18 years	RCT	Supplementation: 300000 IU of cholecalciferol as a loading dose via intramuscular injection, followed by a maintenance dose of 800 IU/day orally, plus oral calcium supplements at a dose of 1000 mg. Duration: 6 months	(1) Increased serum vitamin D levels in the treatment group (P < 0.001); (2) Higher survival rate (64% vs 42%; P < 0.05); and (3) Association between vitamin D supplementation and 6-month survival (HR = 0.895, P < 0.001)
Kim et al[165], 2018	548 patients with chronic HCV (7 RCTs), aged 7-42 years	Meta-analysis	Supplementation: (1) 6 studies used: 1000/1600/2000 IU daily of cholecalciferol; and (2) 1 trial used: 15000 IU weekly of cholecalciferol. Duration: 24 weeks of pegylated interferon alpha and RBV (Peg-IFN-α + RBV) antiviral treatment	(1) Combination of Peg-IFN-α + RBV significantly increased the sustained virological response rate at 24 weeks (RR = 1.30; 95%CI: 1.04-1.62); and (2) Greatest efficacy observed in patients with HCV genotype 1
Hariri and Zohdi[166], 2019	353 patients with MASLD (6 RCTs), aged over 18 years	Systematic review	Supplementation: (1) 4 trials with: 50000 IU of cholecalciferol weekly; (2) 1 trial with: 2000 IU/day of cholecalciferol; and (3) 1 trial with: 25 µg of calcitriol/day. Duration: 6-24 weeks	(1) Improved lipid profile and inflammatory mediators compared to placebo; and (2) Reduction in liver enzymes when combined with calcium carbonate
Grover et al[167], 2021	164 patients with cirrhosis of any etiology (82 control group vs 82 supplementation group), aged 18-60 years	RCT	Supplementation: 60000 IU of cholecalciferol weekly for the first 2 months, followed by 60000 IU monthly for 10 months. Duration: 1 year	Significant increase in 25(OH)D levels in the intervention group compared to placebo
Kong et al[168], 2022	104363 participants (32 RCTs), mostly women, aged 53-85 years	Meta-analysis	Supplementation: 800-4000 IU of cholecalciferol/day. Duration: Follow-up from 9 to 120 months	Significant reduction in risk of falls (RR = 0.91) and osteoporotic fractures (RR = 0.87)
Sakpal et al[169], 2017	81 patients with MASLD (40 control group vs 41 supplementation group), aged 18-70 years	RCT	Supplementation: 600000 IU of vitamin D via a single injection, along with lifestyle modifications (exercise and diet). Duration: 6 months	(1) Significant improvement in ALT levels (87 ± 48 IU/mL to 59 ± 32 IU/mL, P < 0.001) compared to the control group (64 ± 35 to 62 ± 24 IU/mL, P = 0.70); and (2) Significant increase in adiponectin levels (P = 0.018)
Goto et al[170], 2022	Male Wistar rats (four groups of 5-8 rats), 6 weeks old	Preclinical experimental model	Supplementation: 5000 IU/kg and 10000 IU/kg of cholecalciferol in the diet. Duration: 25 weeks	(1) Reduction in hepatic collagen deposition and inflammation; (2) Increased antioxidant activity and Nrf2 protein in the liver; and (3) Higher dose (10000 IU/kg) reduced the number of hepatic adenomas and preneoplastic lesions

SBP: Spontaneous bacterial peritonitis; IU: International unit; HR: Hazard ratio; HCV: Hepatitis C virus; RCT: Randomized controlled trial; RBV: Ribavirin; HR: Hazard ratio; RR: Relative risk; 95%CI: 95% confidence interval; MASLD: Metabolic-associated steatotic liver disease; ALT: Alanine aminotransferase.

Table 4 Overview of clinical and pharmacological factors negatively impacting vitamin D bioavailability

Clinical factors	Pharmacological factors
Liver dysfunction	Long-term therapy with antiepileptic drugs: Phenytoin, carbamazepine, primidone. These can decrease vitamin D levels and increase the risk of bone health problems
Chronic kidney failure	Orlistat: May reduce the absorption of vitamin D from food and supplements by blocking fat absorption
Inherited disorders of vitamin D metabolism	Corticosteroids: May reduce calcium absorption and impair vitamin D metabolism
Therapy for people with obesity or gastric bypass	Thiazide diuretics: Excessive vitamin D supplementation may cause hypercalcemia because thiazides decrease urinary calcium excretion
Gastrointestinal diseases: Hepatobiliary disease, malabsorption, chronic pancreatitis, celiac disease	Bile acid sequestrants: Cholestyramine and colestipol. They may impair vitamin D absorption