Effects of Vitamin Supplementation and Strength Training in Parkinson's Disease

Individuals with Parkinson's disease (PD) have a higher risk of death from coronary artery disease and stroke (Gorell, Johnson, & Rybicki, 1994; Postuma & Lang, 2004). Seventy percent of people with PD suffer from dementia or cognitive impairment. Decreased levels of B vitamins are linked to increased levels of homocysteine (a protein produced in the body) which have been directly linked to heart disease, cerebrovascular accident, dementia, and impaired cognitive function (Miller et al., 2003; Postuma & Lang, 2004). Normalizing the levels of homocysteine and B vitamins in the body has been shown to reduce the risk of these diseases and improve cognitive performance (Miller et al., 2003; Morris, 2003).

Levodopa therapy, which is used to treat individuals with PD, causes elevated homocysteine levels (Blandini et al., 2001; Miller et al., 2003; Postuma & Lang, 2004). The mechanism behind the elevated homocysteine is related to vitamin B status (Miller et al., 2003; Postuma & Lang, 2004). L-dopa undergoes O-methylation and that reaction produces s-adenosylhomocysteine (SAH). SAH is then hydrolyzed and forms homocysteine. Therefore, the more L-dopa that requires 0-methylation, the more homocysteine is produced. Once homocysteine is produced, it gets metabolized back to methionine or to cysteine. In order for it to be metabolized to methionine and cysteine, Vitamin B6, B12 and Folate are needed. If homocysteine can not be metabolized, it accumulates in the body, creating dangerous levels (Miller et al., 2003; Postuma & Lang, 2004).

Undergoing levodopa therapy does not impair homocysteine metabolism but rather causes an increase in homocysteine synthesis, so that it exceeds the body's ability to metabolize it. Thus, levels of Vitamin B12 and Folate need to be higher in individuals on levodopa therapy in order to contend with the need for greater homocysteine metabolism (Miller et al., 2003).

There is ample experimental support for B vitamin supplementation to reduce homocysteine levels in this population (Lamberti et al., 2005; Miller et al., 2003; Postuma & Lang, 2004; Zoccolella et al., 2005). Supplementing B12 (cyanocobalamin) and Folic Acid have been shown to significantly decrease homocysteine levels in individuals with hyperhomocysteinemia on L-dopa therapy (Lamberti et al., 2005). Miller has shown that individuals receiving L-dopa therapy have significantly reduced levels of B6 yet normal cysteine levels. Vitamin B6 is a coenzyme in glutathione synthesis from cysteine. However, vitamin B6 (pyridoxine hydrochloride) supplementation has not been observed in this population therefore the investigators will supplement B6 as well as B12 and Folic Acid. In addition to B vitamins, exercise and strength training have been shown to lower homocysteine levels (Vincent, Bourguignon, & Vincent, 2006) and to increase resting GSH (Elokda & Nielsen, 2007).

Elevated homocysteine has been correlated with decreased glutathione levels (Mosharov, Cranford, & Banerjee, 2000). Glutathione (GSH), in part, is formed by cysteine, causing a direct link between glutathione and homocysteine (see diagram). GSH is one of the most powerful antioxidants in our body. GSH is a reduced form of glutathione which acts as our main defense against Reactive Oxygen Species (ROS) or Free Radicals (FR). ROS contribute to the initiation of many diseases (Viguie et al., 1993). Glutathione disulfide (GSSG) is the oxidized form of GSH. Typically, GSH and GSSG are measured as a ratio (GSH:GSSG) in our blood to help give an immediate understanding of the antioxidant status in our body (Elokda & Nielsen, 2007; Viguie et al., 1993). Individuals with PD have lower levels of GSH at rest than non-PD and lower levels of GSH have been directly correlated with the severity of the disease (Bharath & Andersen, 2005; Maher, 2005).