Killing Pain Not the Same as Building Your Health

(Editorial opinion of the webmaster. If you want a medical opinion, ask a health professional).

I had a group member say that he tried Dr. Lamson's suggested nutritional supplements (urolithin-a, fisetin, cetyl myristoleaste) and hydrogen water.  He did not get pain relief from arthritis in less than a week by taking these supplements and drinking gas-infused water. He suggested these ideas were not as good as acetaminophen or ibuprofen.

A distinction needs to be drawn between pain-relieving pharmaceuticals and extracts of natural substances (supplements) that have health-building effects, including reduction of chronic inflammation.

Chronic inflammation is a persistent, long-term state of inflammation, often lasting for months or even years. It's an abnormal immune response where the inflammatory process doesn't resolve as it should or begins without a clear injury or infection. This prolonged inflammation can damage healthy tissues and contribute to various chronic diseases. 

Pain Relief

If you're in pain, you'd be likely to turn to a non-steroidal anti-inflammatory drug (NSAID) such as aspirin, ibuprofen or celecoxib. Or perhaps to acetaminophen, which has its pain-relieving effects primarily in the central nervous system without significant anti-inflammatory action in the peripheral tissues. Consuming these substances makes your pain go away.

But what if the pain keeps returning? Will you take these pharmaceuticals for months or years? If so, we do so with some caution, especially as we age -- according to reports from my medical research artificial intelligence.

"Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain management in older adults, but they carry significant risks. Older people are at increased risk of serious adverse effects from NSAIDs, including gastrointestinal bleeding, cardiovascular events, kidney injury, and harmful drug interactions. These risks are heightened by age-related changes, comorbidities, and polypharmacy."

"Acetaminophen (paracetamol) is widely used for pain relief in older adults, but recent research highlights several important risks in this population. Older people face increased risks of gastrointestinal bleeding, kidney disease, heart failure, hypertension, and, in rare cases, liver toxicity -- even at standard doses. There is also emerging evidence of potential cognitive and neuropsychiatric effects with recurrent use. Risks increase with long-term or high-dose use."

Pain Relief vs. Cell Optimization

Nutritional supplements are an entirely different animal.

1. They do not have any significant side effects, so they are safer to use. 
2. They act slowly compared to pain killers, because part of their purpose is to help your cells do their job better, which can take some time. Consider giving a nutritional supplement or hydrogen gas a one-month trial so see if you notice a difference.
3. Their mechanism of action is not entirely the same as pain killers.
4. Pain killers and nutritional supplements are not mutually exclusive. You may wish to use either or both if medically appropriate.
5. The supplements and gas therapy mentioned in this article are intended to address the underlying causes of inflammation and its resultant pain. Immediate relief from pain symptoms does not always happen right away and varies among individuals.
6. Results depend on the dosage and frequency.

Let's review the health benefits of each supplement so that you can better judge whether they may be appropriate in your circumstances. According to medical research, these substances may have some merit.

Urolitin-A

Urolithin A is a natural compound produced by gut bacteria from foods rich in ellagitannins, such as pomegranates, berries, and nuts. Recent research highlights its broad health benefits, especially for mitochondrial function, muscle health, inflammation reduction, and age-related conditions.

Mitochondrial and Cellular Health

Enhances mitophagy (the removal of damaged mitochondria), leading to improved mitochondrial function and cellular health in both animal and human studies [1] [2] [3] [4] [5] [6] [7].

Increases mitochondrial gene expression and efficiency, as shown by improved biomarkers in elderly individuals [4] [7].

Muscle Health and Physical Performance

Improves muscle strength and endurance in middle-aged and elderly adults, with clinical trials showing about a 12% increase in muscle strength and better aerobic performance [1] [2] [4] [5] [7].

Promotes muscle protein synthesis and may help prevent muscle atrophy [5].

Anti-Inflammatory and Antioxidant Effects

Reduces inflammation and oxidative stress, which are linked to aging and chronic diseases [1] [8] [5] [9] [10].

Lowers levels of inflammatory markers such as C-reactive protein [4].

Joint and Brain Health

Reduces cartilage degeneration, joint inflammation, and pain in osteoarthritis models, supporting joint health and mobility [1] [3].

Shows neuroprotective effects by reducing neuroinflammation and potentially protecting against neurodegenerative diseases [1] [8] [9] [10].

Other Potential Benefits

May help regulate cholesterol metabolism, support cardiovascular health, and provide anti-cancer and anti-obesity effects [8] [5] [9].

Summary

Urolithin A offers significant health benefits, particularly for mitochondrial function, muscle strength, inflammation reduction, and joint and brain health. Its effects are most pronounced in aging and age-related conditions, making it a promising compound for supporting healthy aging and overall vitality.

Fisetin

Fisetin is a plant-derived flavonoid found in various fruits and vegetables, recognized for its broad range of health benefits. Key research highlights its potential to promote healthy aging, protect against neurodegenerative diseases, support cardiovascular health, and act as an anticancer agent.

Anti-Aging and Senotherapeutic Effects

Fisetin is a potent senolytic, meaning it helps clear senescent (aging) cells, which are linked to age-related diseases and tissue dysfunction. In animal studies, fisetin reduced markers of cellular aging, improved tissue health, and extended both healthspan and lifespan, even when given late in life [1] [2] [3] [4].

Its senotherapeutic action suggests potential for delaying or alleviating age-related conditions [1] [2] [3] [4] [5].

Neuroprotective and Cognitive Benefits

Fisetin shows strong neuroprotective effects in preclinical models of Alzheimer’s, Parkinson’s, Huntington’s, vascular dementia, and other neurological disorders [6] [7] [3] [4].

It acts as an antioxidant, reducing oxidative stress and inflammation in the brain, and helps maintain mitochondrial function and cellular health [6] [7] [3].

Fisetin delays age-related decline in movement and reduces neurotoxicity, supporting its role in brain health and cognitive function [6] [7] [3].

Cardiovascular and Metabolic Health

Fisetin lowers cholesterol by enhancing its excretion through the intestines and activating key regulatory pathways, which may reduce the risk of cardiovascular diseases [8] [9].

It protects heart tissue from ischemia-reperfusion injury (damage caused by restoring blood flow after a blockage) through antioxidant and anti-inflammatory actions, though effectiveness may vary with dosage and health status [8] [9] [4].

Anticancer and Anti-Inflammatory Properties

Fisetin demonstrates anticancer activity by targeting cancer cells, inhibiting tumor growth, and enhancing the effects of other cancer treatments, while sparing healthy cells [4] [5] [10].

It also exhibits anti-inflammatory and cytoprotective effects, contributing to its broad therapeutic potential [2] [4] [5] [10].

Summary

Fisetin offers a wide spectrum of health benefits, including anti-aging, neuroprotective, cardioprotective, anticancer, and anti-inflammatory effects. Its promising results in preclinical studies support further research and potential use as a health-promoting supplement.

Cetyl Myristoleate

Cetyl myristoleate (CM) is a fatty acid ester promoted as a supplement for joint health, particularly in osteoarthritis and other musculoskeletal conditions. Research has focused on its potential anti-inflammatory and joint-protective effects, but findings are mixed and clinical evidence is limited.

Anti-Inflammatory and Joint Health Effects

Animal and Cellular Studies: CM and related cetylated fatty acids have shown the ability to reduce inflammation by lowering levels of inflammatory cytokines (such as IL-6, MCP-1, and TNF) in cell models. They also promote the formation of cartilage cells (chondrogenesis), which may support joint health and repair [1] [2] [3].

Arthritis Models: In animal studies, CM provided protection against experimentally induced arthritis, reducing both the incidence and severity of symptoms. However, the degree of benefit varied, and some studies found only modest effects [2] [3].

Human Studies: Clinical trials in humans with osteoarthritis have not consistently shown that CM is superior to placebo in reducing pain or improving joint function. Some studies found minor improvements, but these were not statistically significant compared to placebo [4] [5].

Supplementation

Supplement Formulations: CM is often combined with other joint health ingredients like methylsulfonylmethane (MSM), glucosamine, and vitamin C in supplements, but the specific contribution of CM to any observed benefits is unclear [6].

Summary

Cetyl myristoleate shows anti-inflammatory and joint-protective effects in animal and cell studies, but there is no strong clinical evidence that it provides significant health benefits for humans with osteoarthritis or joint pain. It is generally safe in supplement form, but its effectiveness remains unproven in well-controlled human trials.

Hydrogen Gas Therapy

Before we review what hydrogen gas therapy does, a few comments are in order.

Your results will vary from others. While some people experience relief within 5-10 minutes after consuming hydrogen gas infused water, others don't. In some, the effect may hardly be noticeable. But that does not mean it is unhelpful. It is helping you but you just can't identify the benefit.

Another factor to consider is the dosage and frequency of use. You can infuse hydrogen into water for 5 minutes, 10 minutes, or more. Ten minutes of infusion will be more effective than five minutes.  By the same token, consuming hydrogen water more than once a day is more effective than only once a day.

Molecular hydrogen gas therapy is an emerging treatment that shows promise for a wide range of health conditions, primarily due to its antioxidant, anti-inflammatory, and neuroprotective effects. It is considered safe, with no major side effects reported, and is being explored for use in many diseases.

Mechanisms of Action

Antioxidant Effects: Molecular hydrogen selectively reduces harmful reactive oxygen species (ROS), such as hydroxyl radicals and peroxynitrite, helping to protect cells from oxidative stress and damage [1] [2] [3] [4] [5] [6].

Anti-inflammatory and Anti-apoptotic: It regulates gene expression to reduce inflammation and cell death, and helps maintain cellular homeostasis [7] [2] [3] [4] [5].

Mitochondrial Protection: Hydrogen may support mitochondrial function and energy metabolism, further reducing oxidative injury [2] [6].

Disease Areas with Reported Benefits

• Neurological Disorders: Neuroprotection in stroke, Alzheimer’s, Parkinson’s, brain injury, depression [8] [9] [2] [4]
• Cardiovascular Diseases: Reduced oxidative stress and inflammation, improved outcomes [1] [3] [4]
• Metabolic Disorders: Benefits in metabolic syndrome, organ injury, and diabetes [1] [3] [4]
• Cancer: Potential supportive therapy, mainly via antioxidant effects [1] [3] [4]
• Respiratory Diseases: Improved outcomes in various lung conditions [1] [3] [4]
• Inflammatory Diseases: Reduced inflammation in a range of conditions [7] [1] [3] [4]

Safety: Hydrogen gas is non-toxic, even at high concentrations, and does not interfere with normal cellular functions [7] [3] [4] [5].

Summary

Molecular hydrogen gas therapy offers a promising, safe approach for treating diseases linked to oxidative stress and inflammation, with particular benefits seen in neurological, cardiovascular, metabolic, and inflammatory conditions. Ongoing research and clinical trials continue to explore its full therapeutic potential.

Citations

Urolithin a References

1. D’Amico, D., Andreux, P., Valdés, P., Singh, A., Rinsch, C., & Auwerx, J. Impact of the Natural Compound Urolithin A on Health, Disease, and Aging.. Trends in molecular medicine. 2021 https://doi.org/10.1016/j.molmed.2021.04.009

2. Ryu, D., Mouchiroud, L., Andreux, P., Katsyuba, E., Moullan, N., Nicolet-Dit-Félix, A., Williams, E., Jha, P., Lo Sasso, G., Huzard, D., Aebischer, P., Sandi, C., Rinsch, C., & Auwerx, J. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nature Medicine. 2016; 22. https://doi.org/10.1038/nm.4132

3. D’Amico, D., Olmer, M., Fouassier, A., Valdés, P., Andreux, P., Rinsch, C., & Lotz, M. Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis. Aging Cell. 2022; 21. https://doi.org/10.1111/acel.13662

4. Singh, A., D’Amico, D., Andreux, P., Fouassier, A., Blanco-Bose, W., Evans, M., Aebischer, P., Auwerx, J., & Rinsch, C. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Reports Medicine. 2022; 3. https://doi.org/10.1016/j.xcrm.2022.100633

5. Zhao, H., Song, G., Zhu, H., Qian, H., Pan, X., Song, X., Xie, Y., & Liu, C. Pharmacological Effects of Urolithin A and Its Role in Muscle Health and Performance: Current Knowledge and Prospects. Nutrients. 2023; 15. https://doi.org/10.3390/nu15204441

6. Tomás-Barberán, F., González‐Sarrías, A., García-Villalba, R., Núñez-Sánchez, M., Selma, M., García-Conesa, M., & Espín, J. Urolithins, the rescue of "old" metabolites to understand a "new" concept: Metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis, and host health status.. Molecular nutrition & food research. 2017; 61 1. https://doi.org/10.1002/mnfr.201500901

7. Andreux, P., Blanco-Bose, W., Ryu, D., Burdet, F., Ibberson, M., Aebischer, P., Auwerx, J., Singh, A., & Rinsch, C. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism. 2019; 1. https://doi.org/10.1038/s42255-019-0073-4

8. Zhang, M., Cui, S., Mao, B., Zhang, Q., Zhao, J., Zhang, H., Tang, X., & Chen, W. Ellagic acid and intestinal microflora metabolite urolithin A: A review on its sources, metabolic distribution, health benefits, and biotransformation. Critical Reviews in Food Science and Nutrition. 2022; 63. https://doi.org/10.1080/10408398.2022.2036693

9. Gandhi, G., Antony, P., Ceasar, S., Vasconcelos, A., Montalvao, M., De Franca, M., Resende, A., Sharanya, C., Liu, Y., Hariharan, G., & Gan, R. Health functions and related molecular mechanisms of ellagitannin-derived urolithins. Critical Reviews in Food Science and Nutrition. 2022; 64. https://doi.org/10.1080/10408398.2022.2106179

10. Xu, J., Yuan, C., Wang, G., Luo, J., , H., Xu, L., Mu, Y., Li, Y., Seeram, N., Huang, X., & Li, L. Urolithins Attenuate LPS-Induced Neuroinflammation in BV2Microglia via MAPK, Akt, and NF-κB Signaling Pathways.. Journal of agricultural and food chemistry. 2018; 66 3. https://doi.org/10.1021/acs.jafc.7b03285

Fisetin References

1. Yousefzadeh, M., Zhu, Y., McGowan, S., Angelini, L., Fuhrmann-Stroissnigg, H., Xu, M., Ling, Y., Melos, K., Pirtskhalava, T., Inman, C., McGuckian, C., Wade, E., Kato, J., Grassi, D., Wentworth, M., Burd, C., Arriaga, E., Ladiges, W., Tchkonia, T., Kirkland, J., Robbins, P., & Niedernhofer, L. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018; 36. https://doi.org/10.1016/j.ebiom.2018.09.015

2. Grynkiewicz, G., & Demchuk, O. New Perspectives for Fisetin. Frontiers in Chemistry. 2019; 7. https://doi.org/10.3389/fchem.2019.00697

3. Park, S., Kim, B., & Park, S. Effects of Fisetin, a Plant-Derived Flavonoid, on Response to Oxidative Stress, Aging, and Age-Related Diseases in Caenorhabditis elegans. Pharmaceuticals. 2022; 15. https://doi.org/10.3390/ph15121528

4. Khan, N., Syed, D., Ahmad, N., & Mukhtar, H. Fisetin: a dietary antioxidant for health promotion.. Antioxidants & redox signaling. 2013; 19 2. https://doi.org/10.1089/ars.2012.4901

5. Elwan, A., El-Masry, S., Habib, D., & Zewail, M. An Insight into Fisetin, The Miraculous Multifaceted Flavonol: Paving the Road for Enhanced Delivery Through Promising Pharmaceutical Nano-Formulations.. Journal of Drug Delivery Science and Technology. 2024 https://doi.org/10.1016/j.jddst.2024.106292

6. Ravula, A., Teegala, S., Kalakotla, S., Pasangulapati, J., Perumal, V., & Boyina, H. Fisetin, potential flavonoid with multifarious targets for treating neurological disorders: An updated review.. European journal of pharmacology. 2021 https://doi.org/10.1016/j.ejphar.2021.174492

7. Hassan, S., Samanta, S., Dash, R., Karpiński, T., Habibi, E., Sadiq, A., Ahmadi, A., & Bungău, S. The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress. Frontiers in Pharmacology. 2022; 13. https://doi.org/10.3389/fphar.2022.1015835

8. Prem, P., Sivakumar, B., Boovarahan, S., & Kurian, G. Recent advances in potential of Fisetin in the management of myocardial ischemia-reperfusion injury-A systematic review.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2022; 101. https://doi.org/10.1016/j.phymed.2022.154123

9. Guo, Y., Liu, B., Geng, Y., Chen, K., Li, J., Yin, X., & Zhang, S. Fisetin, a dietary flavonoid, promotes transintestinal cholesterol excretion through the activation of PPARδ.. Food research international. 2023; 175. https://doi.org/10.1016/j.foodres.2023.113783

10. Kubina, R., Krzykawski, K., Kabała-Dzik, A., Wojtyczka, R., Chodurek, E., & Dziedzic, A. Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review. Nutrients. 2022; 14. https://doi.org/10.3390/nu14132604

Cetyl myristoleate References

1. Hudiță, A., Gălățeanu, B., Dinescu, S., Costache, M., Dinischiotu, A., Negrei, C., Stan, M., Tsatsakis, A., Nikitovic, D., Lupuliasa, D., & Balanescu, A. In Vitro Effects of Cetylated Fatty Acids Mixture from Celadrin on Chondrogenesis and Inflammation with Impact on Osteoarthritis. CARTILAGE. 2018; 11. https://doi.org/10.1177/1947603518775798

2. Diehl, H., & May, E. Cetyl myristoleate isolated from Swiss albino mice: an apparent protective agent against adjuvant arthritis in rats.. Journal of pharmaceutical sciences. 1994; 83 3. https://doi.org/10.1002/JPS.2600830307

3. Hunter, K., Gault, R., Stehouwer, J., & Tam‐Chang, S. Synthesis of cetyl myristoleate and evaluation of its therapeutic efficacy in a murine model of collagen-induced arthritis.. Pharmacological research. 2003; 47 1. https://doi.org/10.1016/S1043-6618(02)00239-6

4. Ha, T., Kang, J., Lee, I., Ahn, C., Lee, C., Lee, S., & Kang, S. Effect of Cis-9-Cetylmyristoleate Containing Fatty Acids Complex Extracted from Vegetable Oils on Knee Pain in Patients with Osteoarthritis. Korean Journal of Family Medicine. 2010; 31. https://doi.org/10.4082/KJFM.2010.31.1.16

5. Morelli, V., Naquin, C., & Weaver, V. Alternative therapies for traditional disease states: osteoarthritis.. American family physician. 2003; 67 2.

6.  CETYL MYRISTOLEATE FORTREATING OSTEOARTHRTS AND OTHER MUSCULOSKELETAL DISEASE CONDITIONS AND INTURES. . 2017

Hydrogen Gas Therapy References

1. Johnsen, H., Hiorth, M., & Klaveness, J. Molecular Hydrogen Therapy—A Review on Clinical Studies and Outcomes. Molecules. 2023; 28. https://doi.org/10.3390/molecules28237785

2. Chen, W., Zhang, H., & Qin, S. Neuroprotective Effects of Molecular Hydrogen: A Critical Review. Neuroscience Bulletin. 2020; 37. https://doi.org/10.1007/s12264-020-00597-1

3. Ohta, S. Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine.. Pharmacology & therapeutics. 2014; 144 1. https://doi.org/10.1016/j.pharmthera.2014.04.006

4. Ge, L., Yang, M., Yang, N., Yin, X., & Song, W. Molecular hydrogen: a preventive and therapeutic medical gas for various diseases. Oncotarget. 2017; 8. https://doi.org/10.18632/oncotarget.21130

5. Huang, L. Molecular hydrogen: a therapeutic antioxidant and beyond. Medical Gas Research. 2016; 6. https://doi.org/10.4103/2045-9912.196904

6. Ishibashi, T. Therapeutic Efficacy of Molecular Hydrogen: A New Mechanistic Insight. Current Pharmaceutical Design. 2019; 25. https://doi.org/10.2174/1381612825666190506123038

7. Zhou, G., Goshi, E., & He, Q. Micro/Nanomaterials‐Augmented Hydrogen Therapy. Advanced Healthcare Materials. 2019; 8. https://doi.org/10.1002/adhm.201900463

8. Wu, C., Zou, P., Feng, S., Zhu, L., Li, F., Liu, T., Duan, R., & Yang, L. Molecular Hydrogen: an Emerging Therapeutic Medical Gas for Brain Disorders. Molecular Neurobiology. 2022; 60. https://doi.org/10.1007/s12035-022-03175-w

9. Pluta, R., Januszewski, S., & Czuczwar, S. Molecular Hydrogen Neuroprotection in Post-Ischemic Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Underlying Mechanisms and Potential for Clinical Implementation—Fantasy or Reality?. International Journal of Molecular Sciences. 2022; 23. https://doi.org/10.3390/ijms23126591

The mission of of seattleseniormen.com and greenwoodmensgroup.com is to provide a supportive environment where men from diverse backgrounds can foster camaraderie, develop friendships, share wisdom, enrich one another's lives -- and contribute to all Seattle communities, including Greenwood, Ballard, Crown Hill, Fremont, Green Lake, Licton Springs, Loyal Heights, Magnolia, Phinney Ridge, Ravenna, Sunset Hill, Wallingford, Wedgwood, Whittier Heights and beyond.