LIVER, NAFLD AND NUTRITIONAL SUPPLEMENTS

by | Jul 18, 2020 | Blog, Blogs, Metabolic Syndrome, MTHFR

Liver, Nafld and nutritional supplements

Non- alcoholic fatty liver disease is the most common liver disease, worldwide.  Numerous studies have reported on the various pathways involved along with some encouraging research on various herbal remedies.

Non-alcoholic Fatty liver disease (NAFLD) is one of the most prevalent causes of liver enzymes enhancement and has a close relationship with obesity, dyslipidemia, type II diabetes, and hypertension. (1)

In a recent randomised, placebo controlled, double blind trial, proved that supplementation with broccoli sprout extract containing glucoraphanin (GR), a Sulphoraphane (SF) effectively improved liver function, thought to be driven by a reduction of oxidative stress.  (2)

Sulphoraphane is also useful in the reduction of the accumulation of lipids due to an alleviation of swelling of mitochondria, brought about by stimulation of mitochondrial function and mitochondrial membrane potential, ATP, and the electron transfer chain, through the NRF2 pathway.  It also assists lipolysis, or the breakdown of fats through upregulation of adipose triglyceride lipase and hormone sensitive lipase.  (3)

Lipases are crucial enzymes that breakdown fats to fatty acids and glycerol or other alcohols.  Lipases breakdown fats in foods to aid absorption in the intestines and are produced in the pancreas, mouth and stomach.

Herbal remedies have long been used for liver health, especially in Asian countries, but now more commonly in Western countries.  Studies on Schisandra chinensis, Silymarin, Dandelion have proven efficacious activity on liver function, in both human and animal studies, in-vitro and in-vivo, with research also being available on the anti-fibrotic activities of plant constituents (4, 5) whilst other herbals have proven significant hepatic protection from liver injury (6).

Diet and lifestyle factors have also been implicated in both the inception and reduction of liver disorders and insulin resistance.  Studies have shown that a 10% weight reduction has proportional improvement in biopsy-confirmed non-alcoholic steatohepatitis, with the Mediterranean Diet showing an association with a reduction in fatty liver and improvement in insulin resistance and a carbohydrate restricted diet reduced showing an even higher percentage reduction in hepatic fat.  Exercise has proven to improve cardiovascular health, reduce fat and hepatic insulin resistance independent of weight loss.  (7)

Natural products rich in triterpenes, flavonoids or polyphenols, have been now established as powerful hepato-protective agents in experimental liver-injury cell and animal models, largely thought to be through anti-oxidant activity.  Some of the natural products containing polyphenols are considered as potential chemo-preventive and hepato-protective agents.  Extensive studies on Silymarin, resveratrol, curcumin and gingko have proven low or no toxicity, easy availability and efficacious activity.  Antioxidant herbals have shown to protect damage by inhibition of fat oxidation (lipid peroxidation) and by increasing antioxidant capacity, blocking free radical generation, reduction of oxidative stress and in the case of Turmeric root and curcuminoids,  inhibit different molecules involved in inflammation such as phospholipase, lipo-oxygenase, (8) cyclooxygenase 2, leukotrienes, (8) thromboxane, prostaglandins, nitric oxide, collagenase, elastase, hyaluronidase, monocyte chemoattractant protein-1, interferon-inducible protein, tumour necrosis factor, and interleukin-12. (9)

Oxygenases can further be grouped into two categories i.e. mono-oxygenases and dioxygenases on the basis of number of oxygen atoms used for oxidation. They play a key role in the metabolism of organic compounds by increasing their reactivity or water solubility or bringing about cleavage of the aromatic ring.  Leukotrienes are inflammatory chemicals the body releases after coming in contact with an allergen or allergy trigger. Leukotrienes cause tightening of airway muscles and the production of excess mucus and fluid. These chemicals play a key role in allergies, allergic rhinitis, and asthma, also causing a tightening of your airways, making it difficult to breathe. Lipase is one of our most vital digestive enzymes released mainly by the pancreas into the small intestine to help the body process and absorb fats. This enzyme is crucial to our health. By breaking down and helping the body to absorb fat, it does so much more for the body than you would expect. Thromboxane is a vasoconstrictor and a potent hypertensive agent, and it facilitates platelet aggregation.  Hepatic injury after hepatic stress is caused by several mechanisms, including inflammatory reaction and microcirculatory disturbance. Levels of thromboxane, a vasoconstrictive eicosanoid, have been shown to increase in systemic circulation after different types of hepatic stress such as endotoxemia, hepatic ischemia-reperfusion, hepatectomy, liver transplantation, haemorrhagic shock and resuscitation, hepatic cirrhosis, and alcoholic liver injury. (10) Recent data implicating lipoxygenases and especially 5-lipoxygenase and its derived products, the leukotrienes, in mounting adipose tissue inflammation and related pathologies in obesity implicates the role these substances play in NAFLD.  (8)

Berberine has extensive research for the treatment of   tumour, diabetes, cardiovascular disease, hyperlipidaemia, inflammation, bacterial and viral infections, cerebral ischemia trauma, mental disease, Alzheimer’s disease, osteoporosis and NAFLD.  (1) Results of a 2016 comparative study between Berberine and lifestyle intervention showed Berberine induced a substantially greater change in serum lipid species compared with mere lifestyle intervention after treatment in NAFLD, (11) along with anti-inflammatory activity noted in a 2020 animal study, with decreases in pro-inflammatory cytokines and liver tissue pathology, biochemical data, and Angptl2 pathway-related genes expression were significantly ameliorated following Berberine administration. (12)

Other remedies, such as Goji Berry, Green Tea, and Garlic have also shown promising positive effects in the treatment of NAFLD (13) along with Artemisia capillaris (Thunb), Gardenia jasminoides (Ellis), and Rheum palmatum and herbs with constituents such as flavonoids, polyphenols, terpenoids, saponins, and alkaloids all have proven effectiveness in the prevention of steatosis and NAFLD through experimental evidence. (14)

 

  1. Imenshahidi M, Hosseinzadeh H. Berberis Vulgaris and Berberine: An Update Review. Phytotherapy Research. 2016;30(11):1745-64.
  2. Kikuchi M, Ushida Y, Shiozawa H, Umeda R, Tsuruya K, Aoki Y, et al. Sulforaphane-rich broccoli sprout extract improves hepatic abnormalities in male subjects. World journal of gastroenterology. 2015;21(43):12457-67.
  3. Lei P, Tian S, Teng C, Huang L, Liu X, Wang J, et al. Sulforaphane Improves Lipid Metabolism by Enhancing Mitochondrial Function and Biogenesis In Vivo and In Vitro. Molecular Nutrition & Food Research. 2019;63(4):1800795.
  4. Gurley BJ, Fifer EK, Gardner Z. Pharmacokinetic herb-drug interactions (part 2): drug interactions involving popular botanical dietary supplements and their clinical relevance. Planta Med. 2012;78(13):1490-514.
  5. Popov Y, Schuppan D. Targeting liver fibrosis: strategies for development and validation of antifibrotic therapies. Hepatology. 2009;50(4):1294-306.
  6. Zhang L, Li HZ, Gong X, Luo FL, Wang B, Hu N, et al. Protective effects of Asiaticoside on acute liver injury induced by lipopolysaccharide/D-galactosamine in mice. Phytomedicine. 2010;17(10):811-9.
  7. Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263-73.
  8. MartC-nez-Clemente M, ClC ria J, Titos E. The 5-lipoxygenase/leukotriene pathway in obesity, insulin resistance, and fatty liver disease2011. 347-53 p.
  9. Singh D, Cho WC, Upadhyay G. Drug-Induced Liver Toxicity and Prevention by Herbal Antioxidants: An Overview. Frontiers in Physiology. 2015;6:363.
  10. Yokoyama Y, Nimura Y, Nagino M, Bland KI, Chaudry IH. Role of Thromboxane in Producing Hepatic Injury During Hepatic Stress. Archives of Surgery. 2005;140(8):801-7.
  11. Chang X, Wang Z, Zhang J, Yan H, Bian H, Xia M, et al. Lipid profiling of the therapeutic effects of berberine in patients with nonalcoholic fatty liver disease. Journal of Translational Medicine. 2016;14(1):266.
  12. Lu Z, He B, Chen Z, Yan M, Wu L. Anti-inflammatory activity of berberine in non-alcoholic fatty liver disease via the Angptl2 pathway. BMC Immunology. 2020;21(1):28.
  13. Xiao J, Fai So K, Liong EC, Tipoe GL. Recent advances in the herbal treatment of non-alcoholic Fatty liver disease. Journal of traditional and complementary medicine. 2013;3(2):88-94.
  14. Yao H, Qiao Y-J, Zhao Y-L, Tao X-F, Xu L-N, Yin L-H, et al. Herbal medicines and nonalcoholic fatty liver disease. World journal of gastroenterology. 2016;22(30):6890-905.