Dr. Ron’s Research Review – July 30, 2014

© 2014

This week’s research review focuses on creatine for Diabetes, PD, HD and muscles.

Parkinson's and Huntington's Disease

Creatine has neuroprotective effects and is now in clinical trials for the treatment of Parkinson's disease (PD) and Huntington's disease (the CREST trial). A phase 2 futility trial in PD showed approximately a 50% improvement in Unified Parkinson's Disease Rating Scale at one year and creatine is now in a phase III clinical trial. (Beal, 2011) (Bender et al., 2006)

Memory in Vegetarians

Young adult females (128) consumed either a placebo or 20 g of creatine supplement for 5 days. In vegetarians, creatine supplementation resulted in better memory. (Benton and Donohoe, 2011)

Muscular Performance in Older Women.

Thirty 58-71 year old women were assigned to a creatine monohydrate (0.3 g/kg for 7 days) or a placebo. Creatine significantly (P < 0.05) increased bench press, leg press, body mass and fat free mass and decreased completion time on the functional tandem gait tests. (Gotshalk et al., 2008)

Type 2 Diabetes

In a 12-week randomized, double-blind, placebo-controlled trial, 25 patients were allocated to receive either creatine (5 g/d) or placebo. HbA1c was significantly reduced. The delta area under the curve of glucose concentration was significantly lower and creatine decreased glycemia at times 0, 30, and 60 min during a meal tolerance test. (Gualano et al., 2011)

Statin Toxicity

Creatine may also prevent statin-induced muscle toxicity. (Shewmon and Craig, 2010)

Dr. Ron


 

Articles

Neuroprotective effects of creatine.
(Beal, 2011) Download
There is a substantial body of literature, which has demonstrated that creatine has neuroprotective effects both in vitro and in vivo. Creatine can protect against excitotoxicity as well as against beta-amyloid toxicity in vitro. We carried out studies examining the efficacy of creatine as a neuroprotective agent in vivo. We demonstrated that creatine can protect against excitotoxic lesions produced by N-methyl-D: -aspartate. We also showed that creatine is neuroprotective against lesions produced by the toxins malonate and 3-nitropropionic acid (3-NP) which are reversible and irreversible inhibitors of succinate dehydrogenase, respectively. Creatine produced dose-dependent neuroprotective effects against MPTP toxicity reducing the loss of dopamine within the striatum and the loss of dopaminergic neurons in the substantia nigra. We carried out a number of studies of the neuroprotective effects of creatine in transgenic mouse models of neurodegenerative diseases. We demonstrated that creatine produced an extension of survival, improved motor performance, and a reduction in loss of motor neurons in a transgenic mouse model of amyotrophic lateral sclerosis (ALS). Creatine produced an extension of survival, as well as improved motor function, and a reduction in striatal atrophy in the R6/2 and the N-171-82Q transgenic mouse models of Huntington's disease (HD), even when its administration was delayed until the onset of disease symptoms. We recently examined the neuroprotective effects of a combination of coenzyme Q10 (CoQ10) with creatine against both MPTP and 3-NP toxicity. We found that the combination of CoQ and creatine together produced additive neuroprotective effects in a chronic MPTP model, and it blocked the development of alpha-synuclein aggregates. In the 3-NP model of HD, CoQ and creatine produced additive neuroprotective effects against the size of the striatal lesions. In the R6/2 transgenic mouse model of HD, the combination of CoQ and creatine produced additive effects on improving survival. Creatine may stabilize mitochondrial creatine kinase, and prevent activation of the mitochondrial permeability transition. Creatine, however, was still neuroprotective in mice, which were deficient in mitochondrial creatine kinase. Administration of creatine increases the brain levels of creatine and phosphocreatine. Due to its neuroprotective effects, creatine is now in clinical trials for the treatment of Parkinson's disease (PD) and HD. A phase 2 futility trial in PD showed approximately a 50% improvement in Unified Parkinson's Disease Rating Scale at one year, and the compound was judged to be non futile. Creatine is now in a phase III clinical trial being carried out by the NET PD consortium. Creatine reduced plasma levels of 8-hydroxy-2-deoxyguanosine in HD patients phase II trial and was well-tolerated. Creatine is now being studied in a phase III clinical trial in HD, the CREST trial. Creatine, therefore, shows great promise in the treatment of a variety of neurodegenerative diseases.

Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial.
            (Bender et al., 2006) Download
Mitochondrial dysfunction plays a major role in the pathogenesis of Parkinson disease (PD). Creatine (Cr) is an ergogenic compound that exerts neuroprotective effects in animal models of PD. We conducted a 2-year placebo-controlled randomized clinical trial on the effect of Cr in 60 patients with PD. Cr improved patient mood and led to a smaller dose increase of dopaminergic therapy but had no effect on overall Unified Parkinson's Disease Rating Scale scores or dopamine transporter SPECT.

The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores.
            (Benton and Donohoe, 2011) Download
Creatine when combined with P forms phosphocreatine that acts as a reserve of high-energy phosphate. Creatine is found mostly in meat, fish and other animal products, and the levels of muscle creatine are known to be lower in vegetarians. Creatine supplementation influences brain functioning as indicated by imaging studies and the measurement of oxygenated Hb. Given the key role played by creatine in the provision of energy, the influence of its supplementation on cognitive functioning was examined, contrasting the effect in omnivores and vegetarians. Young adult females (n 128) were separated into those who were and were not vegetarian. Randomly and under a double-blind procedure, subjects consumed either a placebo or 20 g of creatine supplement for 5 d. Creatine supplementation did not influence measures of verbal fluency and vigilance. However, in vegetarians rather than in those who consume meat, creatine supplementation resulted in better memory. Irrespective of dietary style, the supplementation of creatine decreased the variability in the responses to a choice reaction-time task.

Creatine supplementation improves muscular performance in older women.
            (Gotshalk et al., 2008) Download
Muscle power and strength decrease with age leading to reduced independence and increased health risk from falls. Creatine supplementation can increase muscle power and strength. The purpose of this study was to examine the effects of 7 days of creatine supplementation on body composition, muscular strength, and lower-body motor functional performance in older women. Thirty 58-71 year old women performed three test sessions (T1-T3) each separated by one week. Each session consisted of one repetition maximum tests for bench press and leg press, and isometric hand-grip, tandem gait, upper-body ergometer, and lower-body ergometer tests. Following T2, subjects were assigned to a creatine monohydrate (0.3 g kg body mass(-1) for 7 days) (CR: 63.31 +/- 1.22 year, 160.00 +/- 1.58 cm, 67.11 +/- 4.38 kg) or a placebo (PL: 62.98 +/- 1.11 year, 162.25 +/- 2.09 cm, 67.84 +/- 3.90 kg) supplementation group. CR significantly (P < 0.05) increased bench press (1.7 +/- 0.4 kg), leg press (5.2 +/- 1.8 kg), body mass (0.49 +/- 0.04 kg) and fat free mass (0.52 +/- 0.05) and decreased completion time on the functional tandem gait tests from T2-T3. No significant changes were found for PL on any of the measured variables. No adverse side-effects were reported by either group. Short-term creatine supplementation resulted in an increase in strength, power, and lower-body motor functional performance in older women without any adverse side effects.

Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial.
            (Gualano et al., 2011) Download
Creatine supplementation improves glucose tolerance in healthy subjects. PURPOSES: The aim was to investigate whether creatine supplementation has a beneficial effect on glycemic control of type 2 diabetic patients undergoing exercise training. METHODS: A 12-wk randomized, double-blind, placebo-controlled trial was performed. The patients were allocated to receive either creatine (CR) (5 g.d) or placebo (PL) and were enrolled in an exercise training program. The primary outcome was glycosylated hemoglobin (HbA1c). Secondary outcomes included the area under the curve of glucose, insulin, and C-peptide and insulin sensitivity indexes. Physical capacity, lipid profile, and GLUT-4 protein expression and translocation were also assessed. RESULTS: Twenty-five subjects were analyzed (CR: n=13; PL: n=12). HbA1c was significantly reduced in the creatine group when compared with the placebo group (CR: PRE=7.4 +/- 0.7, POST=6.4 +/- 0.4; PL: PRE=7.5 +/- 0.6, POST=7.6 +/- 0.7; P=0.004; difference=-1.1%, 95% confidence interval=-1.9% to -0.4%). The delta area under the curve of glucose concentration was significantly lower in the CR group than in the PL group (CR=-7790 +/- 4600, PL=2008 +/- 7614; P=0.05). The CR group also presented decreased glycemia at times 0, 30, and 60 min during a meal tolerance test and increased GLUT-4 translocation. Insulin and C-peptide concentrations, surrogates of insulin sensitivity, physical capacity, lipid profile, and adverse effects were comparable between the groups. CONCLUSIONS: Creatine supplementation combined with an exercise program improves glycemic control in type 2 diabetic patients. The underlying mechanism seems to be related to an increase in GLUT-4 recruitment to the sarcolemma.


Creatine supplementation prevents statin-induced muscle toxicity.
            (Shewmon and Craig, 2010) Download

 

References

Beal, MF (2011), ‘Neuroprotective effects of creatine.’, Amino Acids, 40 (5), 1305-13. PubMedID: 21448659
Bender, A, et al. (2006), ‘Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial.’, Neurology, 67 (7), 1262-64. PubMedID: 17030762
Benton, D and R Donohoe (2011), ‘The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores.’, Br J Nutr, 105 (7), 1100-5. PubMedID: 21118604
Gotshalk, LA, et al. (2008), ‘Creatine supplementation improves muscular performance in older women.’, Eur J Appl Physiol, 102 (2), 223-31. PubMedID: 17943308
Gualano, B, et al. (2011), ‘Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial.’, Med Sci Sports Exerc, 43 (5), 770-78. PubMedID: 20881878
Shewmon, DA and JM Craig (2010), ‘Creatine supplementation prevents statin-induced muscle toxicity.’, Ann Intern Med, 153(10) (10), 690-92. PubMedID: 21079234