Khara Lucius, ND

Blog

  • Melatonin in Parkinson’s Disease

    Melatonin in Parkinson’s Disease

    This was a 12 week randomized double-blind placebo controlled trial on melatonin supplementation for people with Parkinson’s Disease (N=60). Participants took either Melatonin 10mg or placebo 1 hour before bedtime for the duration of the trial.

    Melatonin supplementation resulted in numerous favorable changes. This included significant reductions in the following compared to placebo:

    • Unified Parkinson’s Disease Rating Scale part I score (P < 0.001)
    • Pittsburgh Sleep Quality Index ( P = 0.02)
    • Beck Depression Inventory (P = 0.001) and Beck Anxiety Inventory (P = 0.008)
    • hs-CRP (P = 0.003)
    • serum insulin (P = 0.009)
    • HOMA-IR (P = 0.007)
    • Total cholesterol and LDL (P = 0.03 and P = 0.04, respectively)

    People that took melatonin also experienced significant increases in total plasma antioxidant capacity (P < 0.001) and glutathione (P < 0.001).

    Sleep disorders are a common problem for people with PD (including REM-associated sleep behavior disorder), and the expression of melatonin receptors in the substantia nigra of PD patients has been shown to be decreased. Neurotoxin-induced experimental models of PD also demonstrate that melatonin prevents neuron cell death. Whether the effects of melatonin in people with PD are mediated by sleep regulation or other factors, such as antioxidation, is not completely understood.

    Citation:

    Daneshvar Kakhaki et al. Melatonin supplementation and the effects on clinical and metabolic status in Parkinson’s disease: A randomized, double-blind, placebo-controlled trial. Clinical Neurology and Neurosurgery. 2020 May 1; 195:105878.

     

    Link:

    https://www.sciencedirect.com/science/article/pii/S0303846720302213

  • IV Curcumin with Paclitaxel: RDBPCT in Women with Stage III or IV Breast Cancer

    IV Curcumin with Paclitaxel: RDBPCT in Women with Stage III or IV Breast Cancer

    This was a phase II trial comparing IV curcumin with paclitaxel to IV placebo with paclitaxel in women (N=150) with locally advanced or metastatic breast cancer. While participants could have tumors with any receptor status, the majority (57%) had HR+/Her2(-) disease. Patients received IV therapy once weekly for 12 consecutive weeks as follows:

    -Premedication with dexamethasone 8mg
    -Active intervention (Curcumin 300mg with pharmaceutical grade emulsifier) or placebo (riboflavin 200mg) dissolved in 250mL NaCl
    -Paclitaxel 80mg/m2 in 250mL NaCl

    There were no complete responses in either group. However, there were significantly more partial responses in the curcumin group compared to placebo (51% vs 33%; p=0.0145). Three months after completion of treatment, ORR remained higher in the curcumin group (45% for patients who completed treatment with curcumin, versus 28% for those who received placebo; p=0.03), suggesting that efficacy may be maintained even after terminating treatment.

    There were no significant differences in adverse events, with the exception of fatigue, which occurred more often in the placebo group (p=0.05). Allergic reactions did not differ between groups. There were no deaths during the trial.

    Citation:

    Saghatelyan et al. Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: A comparative, randomized, double-blind, placebo-controlled clinical trial.  Phytomedicine. 2020 Apr 18;70:153218

    Link:

    https://www.sciencedirect.com/science/article/pii/S0944711320300507?via%3Dihub

  • PCOS: Curcumin reduces oxidative stress markers

    PCOS: Curcumin reduces oxidative stress markers

    This was a randomized, double-blind, placebo-controlled trial evaluating use of curcumin supplements in overweight or obese women with PCOS and impaired glucose tolerance. Seventy-two patients were recruited and randomized to receive either curcumin at 500mg TID, or a matched placebo, for 3 months. A total of 67 women completed the trial, 34 in the curcumin group, and 33 in the placebo group.

    Curcumin was found to significantly increase glutathione peroxidase levels, including after adjusting for BMI, age, and baseline glutathione peroxidase level (p=0.010). Curcumin also significantly increased gene expression of PGC-1α after adjustment for BMI, age, and baseline values (p=0.031). Effects on sirtuin1 expression and superoxide dismutase were not significant.

    While the authors did not assess for the impact of curcumin on metabolic markers, ovulation, or BMI, a previous trial showed that curcumin at 500mg daily does improve serum insulin (Sohaei et al 2019) in women with PCOS. Perhaps beneficial alterations in oxidation account for a portion of this effect.

    Citation:

    Heshmati et al. The effects of curcumin supplementation on oxidative stress, Sirtuin-1 and peroxisome proliferator activated receptor γ coactivator 1α gene expression in polycystic ovarian syndrome (PCOS) patients: A randomized placebo-controlled clinical trial. Diabetes and Metabolic Syndrome.  2020 Jan 8;14(2):77-82.

    Link:

    

    https://www.sciencedirect.com/science/article/abs/pii/S1871402120300035
    

    


    


  • 


    


    Pilot study on green tea extract and coconut oil to improve functional capacity and anxiety in people with MS
    


    Pilot study on green tea extract and coconut oil to improve functional capacity and anxiety in people with MS
    

    This was a 4 month pilot scale trial which randomized 51 people with multiple sclerosis to either an intervention or control group. The intervention group (N=27) received EGCG 400mg BID plus 30mL coconut oil (roughly 2 TBSP) BID and followed a Mediterranean diet. The control group (n=24) followed the Mediterranean diet only.
    

    At the 4 month mark, both groups experienced significant reductions in BMI and IL6 levels (which the authors attribute to the antioxidant capacity of the Mediterranean diet). Additionally, the intervention group participants had significant reduction in anxiety, and improved functional capacity.
    

    The authors selected coconut oil for this trial due to its high medium chain fatty acid/MCT content, and EGCG for its ability to modulate GABA receptor function as well as T cell and cytokine activity.
    

    Citation:
    

    Platero, J.L.; Cuerda-Ballester, M.; Ibáñez, V.; Sancho, D.; Lopez-Rodríguez, M.M.; Drehmer, E.; Ortí, J.E.R. The Impact of Coconut Oil and Epigallocatechin Gallate on the Levels of IL-6, Anxiety and Disability in Multiple Sclerosis Patients. Nutrients 2020, 12, 305.
    

    Link:
    

    https://www.mdpi.com/2072-6643/12/2/305
    

    


    


  • 


    


    Red clover extract for premenopausal women with breast cancer taking tamoxifen
    


    Red clover extract for premenopausal women with breast cancer taking tamoxifen
    

    In this prospective double-blind randomized placebo-controlled trial, 81 premenopausal women with non-metastatic ER+ breast cancer were given either a red clover extract at 80mg daily (n=42) or a placebo (n=39) for 24 months. All participants were receiving tamoxifen, and were also counseled on both physical activity and Mediterranean diet.
    

    The red clover group had significantly greater improvements in waist circumference as well as BMI (p < 0.0001 for both). Aside from this, both groups experienced significant improvements in HDL (p = 0.01), menopausal symptoms (p < 0.0001), and breast density (p < 0.0001), suggesting that Mediterranean diet and exercise alone were responsible for these changes. Endometrial thickness did not change, and when serum from both groups was applied to ER+ breast cancer cells, there was no alteration in proliferation or estrogen-related gene expression.
    

    It has been my practice to have women who are survivors of ER+ breast cancer avoid supplements containing phytoestrogenic herbs due to lack of safety data, so this (nonetheless small trial) is interesting to see.
    

    Citation:
    

    Ferraris et al. Red clover and lifestyle changes to contrast menopausal symptoms in premenopausal patients with hormone-sensitive breast cancer receiving tamoxifen. Breast Cancer Res Treat. 2020 Jan 24.
    

    Link:
    

    Red clover and lifestyle changes to contrast menopausal symptoms in premenopausal patients with hormone-sensitive breast cancer receiving tamoxifen
    

    


    


  • 


    


    Melatonin supplementation reduces markers of inflammation
    


    Melatonin supplementation reduces markers of inflammation
    

    This was a meta-analysis of RCTs examining the effect of melatonin supplementation on markers of inflammation. Thirteen trials (of 4 weeks duration or longer, comparing melatonin to placebo) were included, with a total of 749 participants. Doses of melatonin used in these trials ranged from 3 to 25mg daily. Trials were conducted in people with a variety of conditions, including T2DM, cancer, obesity, NAFLD, or autoimmune disease.
    

    Melatonin led to decreases in levels of IL6 (p<0.001) and TNF-α (p<0.001), with effects on these markers being more pronounced when melatonin was supplemented for ≥12 weeks and at doses of ≥10 mg/day. Melatonin had a marginal effect on CRP (p=0.06). The authors discuss melatonin’s antioxidant properties as well as effects on the microbiome, and speculate that these factors may contribute to melatonin’s anti-inflammatory effects.
    

    Citation:
    

    Zarezadeh, M., Khorshidi, M., Emami, M. et al. Melatonin supplementation and pro-inflammatory mediators: a systematic review and meta-analysis of clinical trials Eur J Nutr  2019 Nov 2
    

    Link:
    

    https://doi.org/10.1007/s00394-019-02123-0
    

    


    


  • 


    


    Phase I trial of intratumoral or intraperitoneal bromelain and NAC in patients with mucinous peritoneal tumors
    


    Phase I trial of intratumoral or intraperitoneal bromelain and NAC in patients with mucinous peritoneal tumors
    

    In this Phase I trial, participants who had either declined surgery for, or were determined to be inoperable with, mucinous peritoneal tumors were administered a mixture of bromelain and NAC. Doses were based on estimated tumor volume as follows.
    

    For people receiving intratumoral injection:
    

    Bromelain 30mg and NAC 1500mg for tumor volume < 250mL
    

    Bromelain 45mg and NAC 1500mg for tumor volume > 250mL or multiple treatment sites
    

    For people receiving intraperitoneal injection:
    

    Bromelain 45mg and NAC 1500mg for low tumor burden
    

    Bromelain 60mg and NAC 2000mg for extensive tumor burden
    

    A total of 20 patients underwent 28 treatments, with 13 receiving intratumoral treatment, and 7 receiving intraperitoneal treatment. The mean number of surgical procedures subjects had previously undergone was 3.8 (range 2-9). Primary tumor was appendiceal adenocarcinoma (N=10), mucinous ovarian tumor (N=3), colon cancer (N=1), or pseudomyxoma peritonei (N=6).
    

    An objective response to Bromelain and NAC was seen in 30 of 41 treated sites (73.2%), in 85% of patients. Subjects received a mean of 4.2 doses. Adverse events occurred in 85% (N=17) of patients. There were a total of 88 adverse events, with 11 being serious treatment-related adverse events (12.5%). These included fever (35%) and grade II/III pain at drain site or during injection (30%).
    

    This is the first trial of its kind examining such a protocol, with bromelain and NAC designed to essentially dissolve mucinous tumor masses, in humans.
    

     
    

    Citation:
    

    Valle et al. A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study. European Journal of Surgical Oncology 2019 Oct 31. pii: S0748-7983(19)30913-8.
    

    Link:
    

    https://www.sciencedirect.com/science/article/pii/S0748798319309138 
    

     
    

    


    


  • 


    


    Melatonin for diabetics receiving dialysis
    


    Melatonin leads to improvement in markers of glycemic control, cardiometabolic risk, and oxidative stress in diabetic people receiving dialysis
    

    This was a small (N=60) randomized, double-blind placebo controlled trial in adults with diabetes. Participants were randomized to receive either Melatonin 10mg QHS, or a placebo, for 12 weeks. A total of 53 people completed the study (26 in the melatonin group and 27 in the placebo group).
    

    At the completion of the 12 week trial, people who received melatonin experienced the following statistically significant changes:
    

      

    • Decreased FBS (P < .001)
      • 

    • Decreased serum insulin levels (P = .01)
      • 

    • Decreased hsCRP (P = .001)
      • 

    • Increased plasma total antioxidant capacity (P <.001)
      • 

    • Downregulated expression of IL-8 and TNFα, and reduced expression of PPAR-γ (P = .03, P= .008, and P = .03 respectively)
      • 

    

    Melatonin was not found to significantly impact GSH or lipid levels in this trial. Melatonin supplementation was found to be well-tolerated, with no adverse events reported. Participants in the melatonin group also experienced significantly improved sleep function as measured by PSQI (P= .007).
    

    Citation:
    

    

    Ostadmohammadi V et al. The Effects of Melatonin Supplementation on Parameters of Mental Health, Glycemic Control, Markers of Cardiometabolic Risk, and Oxidative Stress in Diabetic Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial. Journal of Renal Nutrition 2019 Oct 6. pii: S1051-2276(19)30313-9
    

    Link:
    

    https://www.jrnjournal.org/article/S1051-2276(19)30313-9/abstract
    

    


    


  • 


    


    NAC rinse reduces xerostomia in head & neck cancer patients receiving chemoradiation
    


    NAC rinse reduces xerostomia in head & neck cancer patients receiving chemoradiation
    

    This was a pilot scale double-blind, placebo-controlled randomized trial of a NAC rinse in people receiving chemoradiation for head and neck cancer. Patients were randomized to use either a 10% NAC rinse (100 mg/mL; 5 mL per rinse) or a sodium chloride placebo rinse in an FDA-approved diluent. Participants were advised to gargle with 5 mL of the solution for 60 seconds, and swish and spit 5 times daily both during radiation and for 2 weeks after completion of chemoradiation. For those in the treatment group, this provided a total NAC dose of 2500mg daily. Thirty-two participants were enrolled, with 17 receiving placebo, and 15 receiving NAC. The majority of subjects were receiving cisplatin.
    

    NAC rinse was better than placebo for ameliorating thickened saliva and mucositis. The NAC group also had improved swallowing scores (p=0.17), and all scores for measures of pain, xerostomia, and trouble with social eating were better in subjects in the NAC group (all p values <0.20). There were no significant differences in adverse events between the NAC and placebo groups.
    

    Citation:
    

    Sio TT, Blanchard MJ, Novotny PJ, Patel SH, Rwigema JM, Pederson LD, McGee LA, Gamez ME, Seeger GR, Martenson JA, Grover Y, Neben Wittich MA, Garces YI, Foote RL, Miller RC, Halyard MY. N-Acetylcysteine Rinse for Thick Secretion and Mucositis of Head and Neck Chemoradiotherapy (Alliance MC13C2): A Double-Blind Randomized Clinical Trial. Mayo Clinic Proceedings. 2019 Aug 9. pii: S0025-6196(19)30396-9.
    

    Link:
    

    https://www.sciencedirect.com/science/article/pii/S0025619619303969
    

     
    

     
    

    


    


  • 


    


    Use of glucosamine supplements associated with reduced risk of CVD
    


    Use of glucosamine supplements associated with reduced risk of CVD
    

    In a large observational study, use of glucosamine supplements was associated with a reduction in CVD. Over 460,000 participants in the UK were surveyed about their health status and supplement use. During a median follow-up period of 7 years, over 10,000 cardiovascular events occurred. After adjusting for age, sex, BMI, lifestyle and dietary factors, use of medications and other supplements, and conditions such as hyperlipidemia and HTN, glucosamine use was associated with a 15% lower risk of total CVD events. People who supplemented with glucosamine had a 9%-22% reduced risk of individual cardiovascular events, including CVD death, coronary heart disease, and CVA. The authors speculate that glucosamine may have a protective effect due to its anti-inflammatory properties, or that glucosamine may act as a calorie restriction mimetic. Participants were not surveyed about the doses of glucosamine they were supplementing with.
    

    Citation:
    

    Ma Hao, Li Xiang, Sun Dianjianyi, Zhou Tao, LeySylvia H, Gustat Jeanette et al. Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank BMJ 2019; 365 :l1628
    

    Link:
    

    https://www.bmj.com/content/365/bmj.l1628