Homocysteine and Leaky Gut
Image retrieved from https://drjockers.com/homocysteine-levels/
It surprises me that homocysteine (Hcy ) is not routinely tested when patients visit their doctors for their annual physical. Homocysteine is an inflammatory amino acid that is produced as a byproduct of protein metabolism. Homocysteine-induced injury to the arterial wall is one of the factors that can initiate the process of atherosclerosis, leading to endothelial dysfunction and eventually to heart attacks and stroke (Jockers, n.d). Elevated homocysteine can cause excessive clotting which can diminish blood flow to major regions of the body; this can lead to heart attacks, dementia, pulmonary embolism, deep vein thrombosis and strokes (Jockers, n.d.).
It is well established that Hcy can enhance the permeability of endothelial cells, and drive inflammatory reactions that can promote damage to the endothelial lining increasing the risk of cardiovascular disease (Ding et al., 2014). What I found even more interesting was a study that was conducted by Ding et. al demonstrating that Hcy can alter the intestinal barrier integrity as well. “Considering the structural and functional similarity between vascular endothelial cells and intestinal epithelial cells, we hypothesized that elevated Hcy levels in the plasma and colonic mucosa is involved in the pathophysiological process of IBD, by affecting intestinal permeability (Ding et al., 2014). How does Hcy influence the gut permeability? According to Ding et. al,
- Hcy can induce the generation of reactive oxygen (ROS) and elicit oxidative damage. Hcy can up-regulate the expressions of many pro-inflammatory factors (TNF-a, IL-6, and IFN-g ) and plays a critical role in the denaturation of key molecules through the hypomethylation of DNA and protein. Therefore, it has been demonstrated that the elevation of Hcy levels in the plasma and colonic mucosa of patients with IBD might be related to the decreased levels of plasma folic acid and Vitamin B12 (VitB12), as well as the gene polymorphism of Hcy metabolic enzymes.
- Damage of the intestinal barrier may aggravate mucosal inflammation and immune responses and is believed to be the key process of infection- and immune factors initiated intestinal infection. As we know, an intact intestinal barrier contributes to maintaining stability of the microflora of the GI tract by inhibiting the migration of intestinal bacteria and toxins, and avoiding damage induced by food antigens and other foreign invaders such as microorganisms. The pro-inflammatory factors, such as TNF-a, IL-1b, IL-6, and IFN-g, can enhance intestinal mucosal permeability by destroying the cell–cell tight junctions.
Dietary modifications to reduce homocysteine
I found it interesting that restricting the intake of methionine could improve intestinal barrier function and promote the recovery of damaged mucosa. “Rao et al. demonstrated that restricting the intake of methionine could improve intestinal barrier function and promote the recovery of damaged mucosa with the colitis control group, suggesting that Hcy can promote the release of pro-inflammatory factors in the colonic tissues of rats with colitis, increase intestinal mucosal permeability, and further aggravate intestinal inflammation (Ding et al., 2014). So the question is, would an elimination diet low in methionine be a short term dietary strategy for people with elevated homocysteine along with a diet higher in B6, B12 and folate? According to Davis (2015), a subset of the population could benefit from a methionine-restricted diet. The people who would benefit from it include:
- People with MTHFR gene variant which can lead to elevated homocysteine to prevent homocysteine accumulation
- Cancer-there is some limited data that suggest that cancer grows less robustly when deprived of methionine
- Depression-high methionine intake can elevate homocysteine and increase a susceptible person’s risk of depression
- Lifespan extension-“Low methionine diets increase metabolic flexibility and overall insulin sensitivity and improve lipid metabolism while decreasing systemic inflammation (Davis, 2015).
- Insulin resistant-methionine restriction can improve insulin sensitivity and reduce adiposity
- If someone has the inherited disorder of homocysteine metabolism (homocystinuria), then of course a low methionine diet would be beneficial.
Foods high in methionine include brazil nuts, lean beef, lean lamb, cheese, turkey, chicken breast, pork, sesame seeds, fish and shellfish, soy beans, eggs, dairy (yogurt), beans (Whitbread, n.d). The most concentrated methionine sources are animal products such as meat, poultry and fish (Davis, 2015). The eating pattern that is lowest in methionine is a purely plant-based or vegan diet.
Methionine-restricted diets allow 800-1200 mg methionine per day for most adults. For methionine alone, 15 mg/kg is thought to be a reasonable lower limit. The downside of a reduced methionine diet is that it could contribute to lower levels of SAM-e which can increase the risk for depression (Davis, 2015). Since a low methionine diet can by default also be a low protein diet, it is important to monitor the protein intake of people who are following a low protein diet and consider plant based sources of proteins to ensure that they are meeting their protein needs and not causing a new problem associated with protein deficiency.
Supplements to reduce homocysteine
B6 is a cofactor for the biosynthesis of cysteine from homocysteine, which them is used to form glutathione, a very important antioxidant for your body! Folate and B12 are cofactors for recycling homocysteine back to methionine. Vitamin B2 and Magnesium are also involved in homocysteine metabolism. Without the proper levels of methylated B6, B12, folate, B2 and magnesium, dangerous levels of homocysteine can build up (Jockers, n.d)
Side note, don’t make the mistake of thinking you can take a supplement and reduce methionine and you will magically lower homocysteine. A poor diet high in sugar and carbohydrates can deplete B vitamins and magnesium. To make matters worse, if you have leaky gut or dysbiosis, you will have trouble with absorption of these nutrients. So healing your gut is key for lowering homocysteine.
Even more, if you have the MTHFR SNP, you may not utilize the folate and B6 as well. So you may need more of these nutrients than someone with a healthy GI tract. IF your homocysteine is above 8 umol/L, it indicates methylation deficiency and elevated risk of CVD. According to doctor Jock, these individuals should supplement with pre-methylated B vitamins such as methyl-folate, methyl-B12, Pyridoxal 5′ Phosphate, riboflavin, trimethylglycine, magnesium and choline
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