@BeautifulDay Can people safely experiment with reaching an optimum doseage of ubiquinol? I'm on 200- 300 mg daily, in 2 doses at present.
Finding a correct dose for anyone and analyzing possible contraindications are very personal, so it's hard to comment on what's right for anyone. For me, in order to survive and make my life better, I do self experiment with things that I believe have the potential for making things better, with little possible downside. I'm a big believer in listening to the body, trying various levels of supplements (like D3 and Ribofalvin (B2)), at different times of the day, and figuring out the amount that best works for me right now.
I find the below study interesting on three points.
1) It's use of high dose Ubiquinol.
2) The finding that "The cerebral metabolic ratio of oxygen measured by 15O2 PET, however, increased by approximately 30% after administration of ubiquinol, suggesting that ubiquinol can improve mitochondrial oxidative metabolism in the brain."
3) "It was notable that his serum creatinine level gradually declined over 36 months (from 1.45 to 0.95 mg/dl)."
Title: "Three-Year Follow-Up of High-Dose Ubiquinol Supplementation in a Case of Familial Multiple System Atrophy with Compound Heterozygous COQ2 Mutations"
"Abstract: We report a 3-year follow-up of high-dose ubiquinol supplementation in a case of familial multiple system atrophy (MSA) with compound heterozygous nonsense (R387X) and missense (V393A) mutations in COQ2. A high-dose ubiquinol supplementation substantially increased total coenzyme Q10 levels in cerebrospinal fluid as well as in plasma. The patient was at the advanced stage of MSA, and the various scores of clinical rating scales remained stable without changes during the 3 years. The cerebral metabolic ratio of oxygen measured by 15O2 PET, however, increased by approximately 30% after administration of ubiquinol, suggesting that ubiquinol can improve mitochondrial oxidative metabolism in the brain. It also suggests the therapeutic potential of ubiquinol for patients with MSA with COQ2 mutations. Further clinical trials of administration of high-dose ubiquinol to MSA patients are warranted."
This is what the study refers to as high dose:
"After baseline assessment, supplementation was started at 600 mg of ubiquinol/day (given once a day), with the dosage increased to 840 mg/day at week 2 and to 1200 mg/day at week 6. The 1200-mg/day dosage was maintained until week 8. When no adverse events were observed during this period, the patient resumed taking 1200 mg of ubiquinol/day after an interval of 8 weeks and remained taking ubiquinol at this same dose for over 3 years to date."
This is how the supplements impacted the patient's labs:
"The analysis of the total CoQ10 levels in plasma and PBMCs revealed a significant increase after 2 weeks of ubiquinol supplementation at 600 mg/day (Table 1). The total CoQ10 levels in plasma and PBMCs remained similar for another 4 weeks at 840 mg/day, and a subsequent 2-week administration of ubiquinol at 1200 mg/day led to substantial increases in the total CoQ10 levels in the plasma and the PBMCs. The CoQ10 level in CSF increased from 0.22 to 3.79 ng/ml after 2 weeks of 840 mg/day, and a similar level of 3.64 ng/ml was observed after 2 weeks of 1200 mg/day. Eight weeks after the last supplementation of ubiquinol, the total CoQ10 levels in plasma, PBMCs, and CSF returned to baseline levels."
Additional information that caught my attention:
"The patient continued to take 1200 mg of ubiquinol/day for over 3 years (Fig. 1). During the entire course, we did not observe any adverse events that were considered to be associated with the ubiquinol supplementation throughout the entire study period. After 36 months of supplementation, evaluation of scores of clinical rating scales (Barthel index, SARA, ICARS, and UMSARS) showed no remarkable changes (Table 2). The brain MRI findings also remained unchanged for the 3 years (Fig. 2). It was notable that his serum creatinine level gradually declined over 36 months (from 1.45 to 0.95 mg/dl) (Fig. 1). His body weight decreased in the first 16 weeks (48.5 to 41.0 kg), but gradually increased over 36 months (41.0 to 46.0 kg) after increasing his daily calorie intake (from 900 to 1500 kcal/day)."
Study Discussion:
"In the present single case study of a patient with familial MSA carrying compound heterozygous mutations in COQ2, administration of high-dose ubiquinol led to a substantial increase in the total CoQ10 levels not only in the plasma and PBMC but also in the CSF. Although previous reports have failed to show the increase in total CSF CoQ10 level by ubiquinone or ubiquinol supplementation, which was caused possibly due to the insufficient dose (300 mg/day) [25], this is the first study showing that ubiquinol supplementation at 840 and 1200 mg/day clearly elevated the total CSF CoQ10 level. CoQ10 has been reported to be poorly absorbed, and its bioavailability varies among formulations [26]. Previous dose escalation studies (up to 3000 mg/day) using chewable tablets of ubiquinone in patients with Parkinson disease, amyotrophic lateral sclerosis, and Huntington disease concordantly showed that the total plasma CoQ10 levels reached the plateau levels of approximately 7.0–7.5 μg/ml after multiple doses of 2400 mg/day [22, 23, 24]. When assessing the bioavailability of ubiquinol in this study, the trough concentrations of total CoQ10 in plasma were 5.04 μg/ml for 600 mg/day, 4.02 μg/ml for 840 mg/day, and 7.86 μg/ml for 1200 mg/day 2 weeks after the daily intake of ubiquinol. Furthermore, another previous study using ubiquinol showed that mean total plasma CoQ10 levels were 2.61 μg/ml for 90 mg/day, 3.66 μg/ml for 150 mg/day, and 6.53 μg/ml for 300 mg/day 2 weeks after a daily intake of ubiquinol [27]. These observations indicate that ubiquinol is better absorbed in the gastrointestinal tract than ubiquinone, and we conclude that the ubiquinol dose of 1200 mg/day is sufficient for achieving a plateau of total CoQ10 level in plasma.
Remarkably, CMRO2 increased without an increase in CBF after administration of 1200 mg of ubiquinol, which suggests that ubiquinol improved cerebral mitochondrial oxidative metabolism. Despite the increase in the CMRO2, however, we did not detect any obvious neurological improvements as determined by the rating scales, presumably owing to the advanced stage of neurodegeneration. Notably, his serum creatinine level gradually declined during the ubiquinol supplementation over 36 months (from 1.45 to 0.95 mg/dl). Because renal involvement has been frequently observed in patients with primary CoQ10 deficiency caused by genetic defects in CoQ10 biosynthesis [28, 29, 30], the renal dysfunction in the patient was likely caused by CoQ10 deficiency and was ameliorated by ubiquinol supplementation. He also showed weight loss in the first 16 weeks of supplementation (48.5 to 41.0 kg). We extensively investigated the cause of his weight loss. However, we did not find chronic infectious diseases, malignancies, extremity edema, pleural effusion, or ascites in this patient during the entire study period. He gradually regained his body weight over 36 months (41.0 to 46.0 kg) after increasing his daily calorie intake. Despite the body weigh changes, his general health condition remained stable."
Study Conclusions:
"The current study suggests that high-dose ubiquinol supplementation (up to 1200 mg/day) is tolerable and improves cerebral mitochondrial oxidative metabolism, which may alter the natural history of MSA progression especially when applied in the early phase of MSA in patients with genetic defects in the CoQ10 biosynthetic pathway. Further clinical trials including administration of ubiquinol to MSA patients carrying heterozygous COQ2 mutations as well as to patients without mutations in COQ2 are warranted. Prospective randomized controlled trials will be undertaken to further extend these initial promising observations."
Full study:
https://link.springer.com/article/10.1007/s12311-017-0846-9
I'm not advocating the high dose that this patient used. Looking at his MRI, the amount of atrophy on the cerebellum was even obvious to me. Therefore, this patient was starting in a position of being pretty far gone already with essentially nothing to lose when he started the study. I don't take that high of a dose. But the study in itself is very interesting.