Khara Lucius, ND

Blog

  • Melatonin for Hot Flashes in Men with Prostate Cancer Receiving ADT

    Melatonin for Hot Flashes in Men with Prostate Cancer Receiving ADT

    Hot flashes are a common complaint related to ADT, reported by 70-80% men receiving this therapy. In this double-blind placebo-controlled RCT, 41 men with prostate cancer receiving ADT were randomized to either placebo or melatonin 3mg BID for 4 weeks.

    Functional Assessment of Cancer Therapy–Prostate (FACT-P) scores significantly improved with use of melatonin (p< 0.05). Melatonin seemed most effective for the reduction of mild hot flashes, with significant improvements seen by week 4 of the trial (p< 0.05). Melatonin was well-tolerated, with no significant adverse events reported by participants.

    Melatonin might offer an especially pertinent support in this group, since men on ADT also report high levels of insomnia in other trials, sometimes related to nocturia or to vasomotor symptoms themselves; other studies demonstrate a reduction in ADT-induced sleep problems with melatonin supplementation at doses similar to the that used in the trial above.

    Citation:

    Etedali A, Hosseni AK, Derakhshandeh A, Mehrzad V, Sharifi M, Moghaddas A. Melatonin in the Management of Mood and Sleep Problems Induced by Androgen Deprivation Therapy in Prostate Cancer Patients: A Randomized Double-blinded, Placebo-controlled Clinical Trial. Iran J Pharm Res. 2022 Sep 30;21(1):e128817. doi: 10.5812/ijpr-128817.

    Link:

    Targeting Side Effects Associated with ADT Using Melatonin: A Randomized Trial on Hot Flashes and Sexual Health in Prostate Cancer Patients

  • Melatonin During Adjuvant Radiation for Women with Early-Stage Breast Cancer

    Melatonin During Adjuvant Radiation for Women with Early-Stage Breast Cancer

    In a randomized, triple-blind, placebo-controlled trial, women with early-stage breast cancer (majority stage I, N= 100) undergoing adjuvant radiation were given either a placebo or melatonin 20mg at bedtime daily, starting on the first day of radiotherapy and continuing through treatment completion. All participants received a total dose of radiotherapy of 50 Gy in 25 fractions (2 Gy per day for all patients).

    At the completion of the trial, women taking melatonin had less fatigue, anxiety, and depression than women in the placebo group (MFI fatigue scores median: 42.5 vs 55; Beck Anxiety Inventory median: 28.5 vs 38; and Beck Depression Inventory median: 29 vs 38; <0.001 for all).

    In analysis of melatonin response by cancer stage (I, II, III), there was no significant difference in the reduction in fatigue scores, suggesting that melatonin is effective regardless of disease stage.

    Citation:

    Sadeghi Yazdankhah S, Javadinia SA, Welsh JS, Mosalaei A. Efficacy of Melatonin in Alleviating Radiotherapy-Induced Fatigue, Anxiety, and Depression in Breast Cancer Patients: A Randomized, Triple-Blind, Placebo-Controlled Trial. Integr Cancer Ther. 2025 Jan-Dec;24:15347354251371705. doi: 10.1177/15347354251371705.

    Link:

    Full text on Pub Med

  • Meta-Analysis of Boswellia for people with T2DM

    Meta-Analysis of Boswellia for people with T2DM

    Boswellia serrata (frankincense) extracts, in particular those with boswellic acids, have anti-inflammatory and insulin-sensitizing effects. In this small meta-analysis, 5 studies with 287 total participants with type 2 daibetes mellitus (T2DM) were included.

    Compared to placebo or controls, use of Boswellia resulted in significant reductions in:

    • HbA1C (SMD: -1.01; 95%CI: -1.55 to -0.46; P=0.00)
    • Total cholesterol (SMD: -0.44; 95%CI: -0.68 to -0.21; P=0.00)
    • Triglycerides (TG) (SMD: -0.42; 95%CI: -0.66 to -0.19; P=0.00)
    • LDL levels (SMD: -0.43; 95%CI: -0.73 to -0.12; P=0.006)

    HDL levels were unaffected by Boswellia treatment (SMD: 0.56, 95%CI: -0.14 to -1.26; P=0.118), and while use of Boswellia did result in a reduction in FBS, this finding was non-significant (SMD: -1.34, 95%CI: -2.68 to 0.00; P=0.05).

    All 5 of the included clinical trials were conducted in Iran. Doses of Boswellia in the included trials ranged from 500mg to 1200mg daily, for durations of 6 to 12 weeks. Mean participant age was 55, and mean participant BMI was 27.01.

    Citation:

    Karimi M, Vakili K, Rashidian P, Razavi-Amoli SK, Akhbari M, Kazemi K. Effect of boswellia (Boswellia serrata L.) supplementation on glycemic markers and lipid profile in type 2 diabetic patients: a systematic review and meta-analysis. Front Clin Diabetes Healthc. 2024 Oct 10;5:1466408.

    Link:

    Full text on Pub Med

  • Combo of Curcumin or Resveratrol with Mediterranean Diet in People with Ulcerative Colitis

    Combo of Curcumin or Resveratrol with Mediterranean Diet in People with Ulcerative Colitis

    This was a small, short-term study in 46 people with mild-to-moderate active ulcerative colitis (UC). Subjects were randomized to one of three groups for 8 weeks:

    • Mediterranean Diet (MD)
    • MD plus curcumin 1600mg daily
    • MD plus resveratrol 500mg daily

    At the completion of the trial, all groups experienced significant reductions in CRP and ESR levels (p <0.05). Only the resveratrol group saw a significant improvement in the neutrophil-to-lymphocyte ratio (NLR) (p =0.01).

    All groups also had significant reductions in the frequency of bowel movements (p= 0.001 for all). Regarding health-related QOL, all groups experienced statistically significant improvements (p<0.05); compared to the other groups, the resveratrol group subjects had even better pain scores (p<0.05), and the curcumin group reported even better social functioning (p<0.05).

    This trial lends support to the concept that the MD is safe and effective in people with mild or moderate UC. Is there a strong advantage to adding curcumin or resveratrol to the MD for these folks? In this trial, aside from some minor differences, there was not a big advantage. It does seem important to note that both curcumin and resveratrol are thought to suffer from poor bioavailability. The formulations of curcumin and resveratrol used in this particular trial do not specify any ingredients or manufacturing methods that would enhance bioavailability.

    Citation:

    Erol Doğan Ö, Karaca Çelik KE, Baş M, Alan EH, Çağın YF. Effects of Mediterranean Diet, Curcumin, and Resveratrol on Mild-to-Moderate Active Ulcerative Colitis: A Multicenter Randomized Clinical Trial. Nutrients. 2024 May 16;16(10):1504. doi: 10.3390/nu16101504.

    Link:

    Full text on Pub Med

  • Fasting Mimicking Diet Reduces Hepatic Fat, Insulin Resistance, and Biological Age

    Fasting Mimicking Diet Reduces Hepatic Fat, Insulin Resistance, and Biological Age  

    In this study, 100 adults were randomized to either their usual diet, or to a fasting-mimicking diet (FMD), for 3 months. Usual diet group participants were simply instructed to follow their regular diet. Fasting participants followed FMD for 5 days per month for 3 consecutive months, using a commercial FMD meal kit (Prolon). Mean age was 42.2 ± 12.5 for usual diet group subjects, and 43.3 ± 11.7 for FMD group subjects. Baseline BMI was comparable: 27.8 ± 5.1 in usual diet group subjects, and 26.6 ± 4.9 for FMD group subjects.

    At the completion of the trial, FMD subjects reduced both total body fat and BMI (p= 0.002 and p= 0.0002). Fifteen subjects also volunteered to complete an MRI to measure abdominal fat distribution. For these volunteers who also had BMI >25, both subcutaneous and visceral fat were reduced from baseline (p =0.008 and p= 0.003). Five participants also had hepatic steatosis (baseline hepatic fat fraction, HFF, of >5%). For these subjects, HFF was reduced from 14.32 ± 5.8% at baseline, to 7.94 ± 4.22%, an almost 50% reduction (p = 0.02).

    Regarding insulin resistance, HOMA-IR was reduced from 1.473 ± 0.85 to 1.209 ± 0.99 with FMD (p = 0.046), and HbA1c went from 5.8 ± 0.3 at baseline, to 5.43 ± 0.404 (p = 0.032).

    To calculate “biological age”, a group of multi-system biomarkers was used (albumin, alkaline phosphatase, serum creatinine, C-reactive protein, Hba1c, systolic BP, and total cholesterol, using the biologic age equation from NHANES III). Median biological age in the FMD participants decreased by close to 2.5 years (p = 0.0007). Change in biologic age was found to be independent of weight loss.

    Citation:

    Brandhorst S, Levine ME, Wei M, Shelehchi M, Morgan TE, Nayak KS, Dorff T, Hong K, Crimmins EM, Cohen P, Longo VD. Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Nat Commun. 2024 Feb 20;15(1):1309. doi: 10.1038/s41467-024-45260-9. PMID: 38378685; PMCID: PMC10879164.

    Link:

    Full text on Pub Med

  • Supplement Quality: Focus on Melatonin

    Supplement Quality: Focus on Melatonin

    In this small study, 25 commercially available melatonin gummies (from the US) were analyzed for contents, with results being as follows:

    • One product had no detectable melatonin, but did have 31.3 mg of CBD instead.
    • In the remaining 24 gummy products, melatonin quantity ranged from 1.3 mg to 13.1 mg per serving
    • For those that actually contained melatonin, the quantity of melatonin ranged from 74% to 347% of the label claim.
    • 22 out of 25 products (88%) were inaccurately labeled
    • Just 3 products (12%) contained a quantity of melatonin within ±10% of the declared quantity.
    • Serotonin was not detected in any of these products.

    Note that a previous study of 16 OTC melatonin supplements in Canada also demonstrated melatonin quantities that fell outside stated label claims (actual dose of melatonin ranged from 17% to 478% of the declared quantity).

    Because OTC supplements are not regulated/approved by the FDA, it is important that clinicians are knowledgeable about supplement quality. Patients should be informed that OTC melatonin supplements may contain uncertain amounts of the target ingredient.

    Citation:

    Cohen PA, Avula B, Wang Y, Katragunta K, Khan I. Quantity of Melatonin and CBD in Melatonin Gummies Sold in the US. JAMA. 2023;329(16):1401–1402. doi:10.1001/jama.2023.2296

    Link:

    2023 JAMA article

  • Curcumin and Vitamin D for People with Lupus: Combo Better Than Either Alone

    Curcumin and Vitamin D for People with Lupus: Combo Better Than Either Alone

    In this small study, people with SLE (N=45) were randomized in double-blind fashion to one of 3 groups for 3 months:

    • Group 1: Vitamin D (1200 IU cholecalciferol) + placebo
    • Group 2: Curcumin (600 mg curcumin + 15,800 mg piperine) + placebo
    • Group 3: Vitamin D (1200IU) + Curcumin (600 mg curcumin + 15,800 mg piperine)

    All patients had low vitamin D levels (serum vitamin D3 levels <30 ng/ml) at the outset of the trial.

    SLEDAI disease scores, fatigue severity scale (FSS), and IL-6 decreased significantly for all 3 groups, while serum TGF-β significantly increased in all 3 groups (p <0.05). However, shanges in SLEDAI, FSS, IL-6, and TGF-β serum levels were similar for groups 1 and 2, while people in group 3 saw the greatest improvements. Changes in SLEDAI score (p = 0.003 and p = 0.008), FSS (p = 0.001 and p <0.001), and TGF-β (p = 0.003 and p = 0.004) serum levels were significantly higher for group 3 versus group 1 or group 2. This is encouraging considering the somewhat modest doses of vitamin D and curcumin provided to participants.

    Citation:

    Wahono CS, Susianti H, Hakim AL, Rosita F, Pratama MZ, Rahman PA, Anshory M. Randomised Clinical Trial Study: The Combination of Vitamin D and Curcumin Piperine Attenuates Disease Activity and Pro-inflammatory Cytokines Levels Insystemic Lupus Erythematosus Patients. Curr Rheumatol Rev. 2024 Jan 31. doi: 10.2174/0115733971276106231226071002. Epub ahead of print. PMID: 38299416.

    Link:

    Epub ahead of print on Pub Med

  • Long-term Use of Adjuvant Melatonin Decreases Fatigue in Women with Breast Cancer

    Long-term Use of Adjuvant Melatonin Decreases Fatigue in Women with Breast Cancer

    In this randomized clinical trial, women with stage I-III breast cancer received either melatonin 18mg daily or placebo, starting 1 week prior to the initiation of adjuvant treatment, and continuing until 2 years post completion of adjuvant treatment. The Brief Fatigue Inventory (BFI) was used pre and post intervention to assess fatigue. 92 subjects completed the trial in the placebo group, and 91 in the melatonin group.

    Baseline BFI scores were no different in the 2 groups. At the completion of the trial, melatonin group subjects had a significantly lower mean fatigue score compared to placebo subjects (2.93 ± 1.04 vs 1.99 ± 1.02, p <0.001, p ≤0.05). There was also a greater reduction in the fatigue score over time in the melatonin group (p ≤0.001). Melatonin was generally well tolerated, with 6 of 102 subjects initially enrolled in the melatonin group withdrawing due to nausea.

    Citation:

    Sedighi Pashaki A, Sheida F, Moaddab Shoar L, Hashem T, Fazilat-Panah D, Nemati Motehaver A, Ghanbari Motlagh A, Nikzad S, Bakhtiari M, Tapak L, Keshtpour Amlashi Z, Javadinia SA, Keshtpour Amlashi Z. A Randomized, Controlled, Parallel-Group, Trial on the Long-term Effects of Melatonin on Fatigue Associated With Breast Cancer and Its Adjuvant Treatments. Integr Cancer Ther. 2023 Jan-Dec;22:15347354231168624. doi: 10.1177/15347354231168624. PMID: 37139718; PMCID: PMC10161337.

    Link:

    Integrative Cancer Therapies

  • Curcumin and COVID-19: A Systematic Review of Clinical Trials

    Curcumin and COVID-19: A Systematic Review of Clinical Trials

    In this systematic review, 8 studies that examined use of curcumin (specifically nano-curcumin formulations) in people with COVID-19, with a total of 569 participants, were included for review. Nano-curcumin supplementation had no significant effect on CRP, hs-CRP, TNF-α, or IL-6 levels compared to placebo. However, IL-6 and IL-1β expression were significantly reduced by nano-curcumin. Compared to controls, the duration of hospitalization as well as mortality rate were significantly lower for those receiving nano-curcumin. Lymphocyte count was significantly increased with nano-curcumin as well.

    Nano-curcumin also had favorable effects on clinical outcomes and symptoms, including O2 sat, sputum, chest pain, wheeze, dyspnea, fever, cough, chills, myalgia, and olfactory/taste disturbances. Nano-curcumin was well tolerated, with no major adverse effects.

    Citation:

    Shojaei M, Foshati S, Abdi M, Askari G, Sukhorukov VN, Bagherniya M, Sahebkar A. The effectiveness of nano-curcumin on patients with COVID-19: A systematic review of clinical trials. Phytother Res. 2023 Feb 17. doi: 10.1002/ptr.7778.

    Link:

    https://onlinelibrary.wiley.com/doi/10.1002/ptr.7778

  • Mediterranean Diet and Response to Checkpoint Inhibitors

    Mediterranean Diet and Response to Checkpoint Inhibitors

    In a multicenter study (in the UK and the Netherlands) conducted to assess the association between immune checkpoint blockade and diet, 91 people with advanced melanoma completed an FFQ before initiating treatment.

    A positive association between a Mediterranean diet (high in whole grains, fish, nuts, fruit, and vegetables) and treatment response was observed. Both overall response rate (ORR) and progression free survival (PFS) were positively associated with Mediterranean diet score. A max Mediterranean diet score of 5 was associated with the highest probability of tx response, 0.74 for PFS (p =0.01) and 0.77 for ORR (p= 0.02).

    The importance of the gut microbiome in checkpoint blockade treatment response has been previously demonstrated, and the Mediterranean diet is rich in foods known to influence the gut microbiome, including fiber (which would support beneficial SCFA production, high levels of which are also associated with response to immunotherapy), polyphenols, and antioxidants. These interesting findings add to the body of research indicating dietary/gut factors influence immunotherapy treatment outcomes.

    Citation:

    Bolte LA, Lee KA, Björk JR, Leeming ER, Campmans-Kuijpers MJE, de Haan JJ, Vila AV, Maltez-Thomas A, Segata N, Board R, Harries M, Lorigan P, de Vries EGE, Nathan P, Fehrmann R, Bataille V, Spector TD, Hospers GAP, Weersma RK. Association of a Mediterranean Diet With Outcomes for Patients Treated With Immune Checkpoint Blockade for Advanced Melanoma. JAMA Oncol. 2023 Feb 16:e227753. doi: 10.1001/jamaoncol.2022.7753.

    Link:

    https://jamanetwork.com/journals/jamaoncology/fullarticle/2801594