Pursuant to the research: Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/CFS It should be noted that the pyruvate dehydrogenase function is dependent upon thiamine (B1), a deficiency of which could be of serious concern in ME/CFS. "Humans store between 25-30mg of thaimine, much less than other animals. Due to thiamine being a water soluble nutrient, depletion can occur in 14-18 days." "Cellular roles of Thiamine Thiamine has several roles in cellular glucose metabolism as it functions as a cofactor for various enzyme complexes. The pyruvate dehydrogenase(PDH) and alpha ketoglutarate dehydrogenase(a-KGDH) enzyme complexes are important thiamine dependent enzyme complexes that help liberate energy from glucose in the citric acid cycle of mitochondria. During glycolysis in the cytosol, glucose is converted in to 2 pyruvate molecules that enter the mitochondria. Inside the mitochondria, pyruvate is converted in to acetyl CoA by the PDH complex so that it can enter the citric acid cycle. This step requires thiamine diphosphate as a coenzyme. This is important for 2 reasons. In neurons, acetyl CoA comes predominantly from glucose and is necessary for the synthesis of the neurotransmitter acetylcholine, which we will cover later. Secondly, in all cell types, insufficient thiamine decreases PDH activity and lactate accumulates in the cell and pours out in to the circulation. Blood lactate is known to be elevated in Type 2 diabetics(2) and high blood lactate levels induce insulin resistance in skeletal muscle(3)." "The role of a-KGDH in the citric acid cycle is also of importance as this enzyme complex is necessary for the synthesis of the neurotransmitters GABA, glutamate, and aspartate. Furthermore, the altered glucose metabolism that accompanies a deficiency in the activity of PDH and a-KGDH can lead to mitochondrial damage and eventual cell death(4)." "Another area of glucose metabolism where thiamine is important is the pentose phosphate pathway. The pentose phopshate pathway is an anabolic pathway of glucose metabolism that creates NADPH or R5P based on cellular needs. For a more thorough look at this process, check out this blog. Understanding the pentose phosphate pathway is crucial for understanding hormonal balance and how adrenal function can be affected by thiamine deficiency so I urge you to check that blog out." "One study showed that inducing thiamine deficiency in rats led to hyperstimulation of the zona fasciculata of the adrenal glands in 2 weeks causing increased corticosterone output followed by complete exhaustion in 4 weeks(8)." "A study in humans found thiamine injections prevented functional adrenal gland exhaustion during and after surgical stress(10) " The above quotes and further details are found at : http://synergyhw.blogspot.com/2015/04/the-importance-of-addressing-thiamine.html Got Thiamine - (B1)?