Over the years, it has become clear that an increased blood level of the amino acid, homocysteine, especially levels >14 μmol/l, is associated with increased risk for an astounding variety of human disease: cardiovascular events and death, stroke, cancer, migraine headaches, seizures, macular degeneration, diabetic retinopathy, failed in vitro fertilization, cognitive dysfunction, and depression. Homocysteine levels can be reduced by a number of strategies. The most common method is to supplement B vitamins B6, B9 (folate or folic acid), and B12, sometimes B2 (riboflavin).

A total of eight human clinical trials have been performed using a variety of different B vitamin regimens that reduce blood levels of homocysteine by an average of 25%. Results across all 8 trials: no reduction in cardiovascular events, strokes, cancers, or deaths.

Why the disconnect? How can something be confidently associated with a long list of health conditions but yield no benefit when reduced? My view is that increased homocysteine levels can indeed be reduced with B vitamins, but lack of dietary B vitamins is not the driving factor for increased risk for disease, but is just a side phenomenon.

Consider this: The gastrointestinal (GI) microbiome is a source of vitamins B1, B2, B3, B5, B6, B9, and B12—but not when you have a case of colonic dysbiosis or small intestinal bacterial overgrowth, SIBO. In these situations, people experience a shift towards excessive Firmicutes species and lack of beneficial species such as Faecalibacterium prausnitzii, Lactobacillus species, and non-pathogenic E. coli. This unhealthy shift in microbial species means that there are fewer able to produce B vitamins. In other words, an adverse shift in microbes away from B-vitamin producing species may be the underlying cause of higher levels of homocysteine. Reduce homocysteine by supplementing B vitamins but you will be left with dysbiosis or SIBO and the accompanying endotoxemia. Recall that endotoxemia has been associated with heart disease, stroke, various cancers, depression—many of the same conditions associated with higher levels of homocysteine. Take B vitamins, reduce homocysteine, and you will still be at risk for heart disease. Take B vitamins, reduce homocysteine, and you can still be depressed. And you remain at higher risk for all the consequences of uncorrected SIBO and endotoxemia: weight gain, accumulation of abdominal visceral fat, higher blood sugar and blood pressure, anxiety, autoimmune diseases, neurodegenerative diseases like multiple sclerosis, and others. The homocysteine-B vitamin connection may therefore have been a major distraction that took everyone’s attentions away from the real underlying processes causing these phenomena. It’s a situation similar to cholesterol, the false marker for heart disease that took everyone’s attention away from the real causes of heart disease, explaining why there has been no major reduction in the incidence of heart attacks, sudden cardiac death, and heart procedures despite the nationwide push to reduce cholesterol values. Reduce homocysteine and you are chasing a bogeyman, not the real monster threatening your health.

If a low blood level of folate or B6 or B12 is identified, or if a MTHFR variant is identified, there is no harm in supplementing with the deficient nutrient, since there are other reasons for deficiency such as not consuming sufficient animal matter for vitamin B12, or gastric atrophy from autoimmune gastritis or H, pylori infestation. And there are also rare genetic variants that can drive higher homocysteine levels. But if a higher level of homocysteine is identified, it is worth asking whether dysbiosis or SIBO is the cause and that the solution may not be B vitamin supplementation. Addressing the colonic dysbiosis or SIBO is the potential solution. If you have been following my conversations, you know that our number one choice for management of SIBO is my SIBO Yogurt made with three bacterial species/strains that release bacteriocins that kill fecal microbes in the small intestine, a strategy that has been effective about 90% of the time in normalizing breath hydrogen gas.