Dr. Ron’s Research Review – November 3, 2010

This week’s research review contains articles on Leucine and diabetes; Manganese; and a review article on Maca (L. meyenii) for improving sexual function.


Branched-chain amino acids, particularly leucine, play a critical role in controlling protein synthesis. (Yang, Chi et al. 2010)

In pancreatic beta cells, leucine acutely stimulates insulin secretion by serving as both metabolic fuel and allosteric activator of glutamate dehydrogenase to enhance glutaminolysis. (Yang, Chi et al. 2010)


Manganese is considered one of the least toxic of the trace elements when consumed orally. Manganese poisoning has been found among workers in the battery manufacturing industry. (Hathcock 2004)

Manganese is required for normal thyroid function and is involved in the formation ofthyroxin. Tissue mineral analysis (TMA) studies have revealed low manganese levels in hypothyroid patients. (Watts 1990)

Individuals suffering from manganese toxicity exhibit several symptoms, including mitochondrial dysfunction, which are similar to those frequently observed in cases of Parkinson’s disease. (Dobson, Erikson et al. 2004)


Maca (L. meyenii) for improving sexual function (Shin, Lee et al. 2010)

Dr. Ron


Leucine metabolism in regulation of insulin secretion from pancreatic beta cells

            (Yang, Chi et al. 2010) Download

Leucine, a branched-chain amino acid that must be supplied in the daily diet, plays an important role in controlling protein synthesis and regulating cell metabolism in various cell types. In pancreatic beta cells, leucine acutely stimulates insulin secretion by serving as both metabolic fuel and allosteric activator of glutamate dehydrogenase to enhance glutaminolysis. Leucine has also been shown to regulate gene transcription and protein synthesis in pancreatic islet beta cells via both mTOR-dependent and -independent pathways at physiological concentrations. Long-term treatment with leucine has been shown to improve insulin secretory dysfunction of human diabetic islets via upregulation of certain key metabolic genes. In vivo, leucine administration improves glycemic control in humans and rodents with type 2 diabetes. This review summarizes and discusses the recent findings regarding the effects of leucine metabolism on pancreatic beta-cell function.

Manganese neurotoxicity

(Dobson, Erikson et al. 2004) Download
Manganese is an essential trace element and it is required for many ubiquitous enzymatic reactions. While manganese deficiency rarely occurs in humans, manganese toxicity is known to occur in certain occupational settings through inhalation of manganese-containing dust. The brain is particularly susceptible to this excess manganese, and accumulation there can cause a neurodegenerative disorder known as manganism. Characteristics of this disease are described as Parkinson-like symptoms. The similarities between the two disorders can be partially explained by the fact that the basal ganglia accumulate most of the excess manganese compared with other brain regions in manganism, and dysfunction in the basal ganglia is also the etiology of Parkinson's disease. It has been proposed that populations already at heightened risk for neurodegeneration may also be more susceptible to manganese neurotoxicity, which highlights the importance of investigating the human health effects of using the controversial compound, methylcyclopentadienyl manganese tricarbonyl (MMT), in gasoline to increase octane. The mechanisms by which increased manganese levels can cause neuronal dysfunction and death are yet to be elucidated. However, oxidative stress generated through mitochondrial perturbation may be a key event in the demise of the affected central nervous system cells. Our studies with primary astrocyte cultures have revealed that they are a critical component in the battery of defenses against manganese-induced neurotoxicity. Additionally, evidence for the role of oxidative stress in the progression of manganism is reviewed here.

Published Official Reviews of Manganese Safety by the Council for Responsible Nutrition.


Safety of Manganese

         Hathcock 2004 Download

The Nutritional Relationships of Manganese

         Watts 1990 Download

Maca (L. meyenii) for improving sexual function: a systematic review

            (Shin, Lee et al. 2010) Download

BACKGROUND: Maca (Lepidium meyenii) is an Andean plant of the brassica (mustard) family. Preparations from maca root have been reported to improve sexual function. The aim of this review was to assess the clinical evidence for or against the effectiveness of the maca plant as a treatment for sexual dysfunction. METHODS: We searched 17 databases from their inception to April 2010 and included all randomised clinical trials (RCTs) of any type of maca compared to a placebo for the treatment of healthy people or human patients with sexual dysfunction. The risk of bias for each study was assessed using Cochrane criteria, and statistical pooling of data was performed where possible. The selection of studies, data extraction, and validations were performed independently by two authors. Discrepancies were resolved through discussion by the two authors. RESULTS: Four RCTs met all the inclusion criteria. Two RCTs suggested a significant positive effect of maca on sexual dysfunction or sexual desire in healthy menopausal women or healthy adult men, respectively, while the other RCT failed to show any effects in healthy cyclists. The further RCT assessed the effects of maca in patients with erectile dysfunction using the International Index of Erectile Dysfunction-5 and showed significant effects. CONCLUSION: The results of our systematic review provide limited evidence for the effectiveness of maca in improving sexual function. However, the total number of trials, the total sample size, and the average methodological quality of the primary studies were too limited to draw firm conclusions. More rigorous studies are warranted.