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Probiotic Combo With Flax and Wheat Germ Oil

This randomized control trial demonstrated that co-administration of a live multi-strain probiotic mixture with omega-3 fatty acids once daily for 8 weeks to patients with NAFLD can significantly reduce liver fat as measured by the Fatty Liver Index (FLI). This combination also improved serum lipid levels, metabolic profiles, and reduced chronic systemic inflammation. However, liver stiffness (LS) did not show significant changes in either group during the study. Outcomes align with those of Mofidi et al., who used similar measures to evaluate the efficacy of symbiotic supplementation in lean NAFLD patients. In their trial, after 28 weeks of administration, the reduction in hepatic steatosis and fibrosis measured by transient elastography (Fibroscan®) was significantly greater in the symbiotic group compared to the placebo group. The difference in LS results compared to our study could be attributed to the longer supplementation period in their study.

Previous reporting data from a randomized control trial with a similar design and endpoints, showing the beneficial effects of a probiotic formulation alone for managing NAFLD. After further investigations, this study found that supplementing live probiotic strains with omega-3 fatty acids leads to a more pronounced reduction in FLI and chronic inflammatory markers. Moreover, this combination significantly improves serum lipid parameters.

The beneficial effects of probiotic supplementation containing different Lactobacillus and Bifidobacterium strains in NAFLD have been demonstrated in several randomized control trials and summarized in recent meta-analyses. These studies showed that probiotic therapy significantly decreased transaminase levels, a marker of chronic systemic response (TNF-α), and improved lipid metabolism parameters such as total cholesterol (TC) and high-density lipoprotein (HDL).

Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) have also been studied as a treatment for NAFLD. Preclinical studies demonstrated that dietary n-3 PUFAs prevent hepatic steatosis by down-regulating sterol regulatory element-binding protein 1c (SREBP-1c), a key transcription factor in lipogenesis, and up-regulating peroxisome proliferator-activated receptor (PPAR-α), which regulates genes involved in fatty acid oxidation. The excessive production of reactive oxygen species due to mitochondrial dysfunction causes lipid peroxidation, triggering inflammatory processes by activating redox-sensitive transcriptional factors like NF-κB, leading to necro-inflammation and activation of stellate cells, which causes fibrogenesis in NASH. Recent animal studies showed that LC n-3 PUFAs supplementation decreased hepatic oxidative stress by improving antioxidant status, restoring antioxidant enzyme activities and glutathione levels, and prevented high-fat-induced hepatic steatosis and inflammation by inhibiting NF-κB and decreasing proinflammatory cytokines TNF-α and IL-1β.

Recent randomized control trials indicate that n-3 LC polyunsaturated fatty acids supplementation, combined with protein meal replacement under calorie-restricted dietary conditions or lifestyle modification, significantly reduces waist circumference and exerts beneficial effects on metabolic parameters, including triglyceride (TG) levels, HOMA-IR, and IL-6.

Castro et al. analyzed 17 studies investigating the effects of n-3 PUFAs on markers of NAFLD. They found that twelve studies reported a decrease in liver fat and other NAFLD markers after n-3 PUFAs supplementation. However, five studies also involved dietary restriction and exercise alongside n-3 PUFA supplementation, indicating that n-3 PUFAs improve NAFLD independently of weight loss. The lack of improvement in some studies may be due to short duration, poor compliance, patient-specific factors, and the sensitivity of the methods used.

Three meta-analyses of randomized control trials of n-3 PUFA treatment for NAFLD examined 3 to 9 clinical trials each, involving up to 561 total patients. The n-3 PUFA dose ranged from 0.83 to 6.4 g/d, and the treatment period lasted from 2 to 18 months. The overall outcome indicates that n-3 PUFA treatment improves plasma markers of hepatic damage and TG levels but had inconsistent effects on plasma markers for cholesterol (TC, LDL-C, and HDL-C).

Finally, Rajkumar et al. compared the effects of probiotics VSL#3 with omega-3 fatty acids to single-arm therapy in apparently healthy overweight adult volunteers in a placebo-controlled double-blind trial. The study showed that VSL#3 supplementation increased Lactobacilli and Bifidobacteria and reduced Gram-negative bacteria, while the combination of probiotics and omega-3 fatty acids improved insulin sensitivity and reduced hsCRP levels more than probiotics alone.