The methylation cycle shows up in all kinds of disease processes. Researchers had linked high homocysteine levels with NASH, non-alcoholic steatohepatitis, in other studies. In this mouse study, they found that the addition of B12 and Folate not only lowered homocysteine levels, but also lowered the frequency of homocysteine being attached to liver proteins and damaging them. The additional B12 and folate set off a cascade of events in which the NASH fatty liver improved.
NASH affects millions of individuals as a part of metabolic syndrome (also include high triglycerides, high sugars, high blood pressure, and some hormonal effects). This inflammation in the liver cells which lead to elevations in blood test markers can ultimately lead to liver failure if untreated. Several factors including obesity, diet, inflammation, and toxins can play a role in the development of this widespread condition.
Prior research indicated that higher levels of homocysteine correlated with worsened NASH cases. Homocysteine is a non-protein amino acid (we don’t use it in our body protein) which plays a key role in the methylation cycle. This metabolic cycle called methylation uses B12, Folate, and other nutrients to run homocysteine through steps converting it into methionine and then into s-adenosyl methionine, known as SAMe (pronounced “Sam- EE”). SAMe is used in dozens of other metabolic processes from detoxification to making cell membrane fats to metabolizing hormones to metabolizing neurotransmitters and more.
Given the liver’s role in detoxification and its high need for phosphatidylcholine (made using SAMe), it I not surprising that this critical organ would be negatively affected by an inadequate methylation cycle. Prior research also indicated that higher levels of homocysteine leftover when insufficient B12 or Folate is available can cause the homocysteine to be attached to cell proteins. This seems to turn off a process called autophagy. This critical autophagy process allows cells to recycle themselves and be replaced by newer, healthier cells. Without this, apparently, NASH is more likely.
In this mouse study, supplying B12 and Folate not only lowered homocysteine, but also reversed the metabolic processes which were abnormal in the NASH mice. Further studies will need to be done in humans with NASH, but this supports our regular practice of evaluating our patient’s B12 and Folate levels as well as optimizing these levels to help support the methylation cycle and all its downstream functions. Helping patients restore healthier more abundant lives requires this level of attention and care.
Madhulika Tripathi, Brijesh Kumar Singh, Jin Zhou, Keziah Tikno, Anissa Widjaja, Reddemma Sandireddy, Kabilesh Arul, Siti Aishah Binte Abdul Ghani, George Goh Boon Bee, Kiraely Adam Wong, Ho Jia Pei, Shamini Guna Shekeran, Rohit Anthony Sinha, Manvendra K. Singh, Stuart Alexander Cook, Ayako Suzuki, Teegan Reina Lim, Chang-Chuen Cheah, Jue Wang, Rui-Ping Xiao, Xiuqing Zhang, Pierce Kah Hoe Chow, Paul Michael Yen. Vitamin B12 and folate decrease inflammation and fibrosis in NASH by preventing Syntaxin 17 homocysteinylation. Journal of Hepatology, 2022; DOI: 10.1016/j.jhep.2022.06.033
Thanks to Science Daily:
Duke-NUS Medical School. “B vitamins can potentially be used to treat advanced non-alcoholic fatty liver disease.” ScienceDaily. ScienceDaily, 5 August 2022. <www.sciencedaily.com/releases/2022/08/220805091251.htm>.
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Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.