{"doi":"10.3390/nu12123727","title":"A Theacrine-Based Supplement Increases Cellular NAD+ Levels and Affects Biomarkers Related to Sirtuin Activity in C2C12 Muscle Cells In Vitro","abstract":"<jats:p>There is evidence in rodents to suggest that theacrine-based supplements modulate tissue sirtuin activity as well as other biological processes associated with aging. Herein, we examined if a theacrine-based supplement (termed NAD3) altered sirtuin activity in vitro while also affecting markers of mitochondrial biogenesis. The murine C2C12 myoblast cell line was used for experimentation. Following 7 days of differentiation, myotubes were treated with 0.45 mg/mL of NAD3 (containing ~2 mM theacrine) for 3 and 24 h (n = 6 treatment wells per time point). Relative to control (CTL)-treated cells, NAD3 treatments increased (p &lt; 0.05) Sirt1 mRNA levels at 3 h, as well as global sirtuin activity at 3 and 24 h. Follow-up experiments comparing 24 h NAD3 or CTL treatments indicated that NAD3 increased nicotinamide phosphoribosyltransferase (NAMPT) and SIRT1 protein levels (p &lt; 0.05). Cellular nicotinamide adenine dinucleotide (NAD+) levels were also elevated nearly two-fold after 24 h of NAD3 versus CTL treatments (p &lt; 0.001). Markers of mitochondrial biogenesis were minimally affected. Although these data are limited to select biomarkers in vitro, these preliminary findings suggest that a theacrine-based supplement can modulate select biomarkers related to NAD+ biogenesis and sirtuin activity. However, these changes did not drive increases in mitochondrial biogenesis. While promising, these data are limited to a rodent cell line and human muscle biopsy studies are needed to validate and elucidate the significance of these findings.</jats:p>","journal":"Nutrients","year":2020,"id":638320,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":761831,"name":"Shelby C. 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Herein, we examined if a theacrine-based supplement (termed NAD3) altered sirtuin activity in vitro while also affecting markers of mitochondrial biogenesis. The murine C2C12 myoblast cell line was used for experimentation. Following 7 days of differentiation, myotubes were treated with 0.45 mg/mL of NAD3 (containing ~2 mM theacrine) for 3 and 24 h (n = 6 treatment wells per time point). Relative to control (CTL)-treated cells, NAD3 treatments increased (p &lt; 0.05) Sirt1 mRNA levels at 3 h, as well as global sirtuin activity at 3 and 24 h. Follow-up experiments comparing 24 h NAD3 or CTL treatments indicated that NAD3 increased nicotinamide phosphoribosyltransferase (NAMPT) and SIRT1 protein levels (p &lt; 0.05). Cellular nicotinamide adenine dinucleotide (NAD+) levels were also elevated nearly two-fold after 24 h of NAD3 versus CTL treatments (p &lt; 0.001). Markers of mitochondrial biogenesis were minimally affected. Although these data are limited to select biomarkers in vitro, these preliminary findings suggest that a theacrine-based supplement can modulate select biomarkers related to NAD+ biogenesis and sirtuin activity. However, these changes did not drive increases in mitochondrial biogenesis. While promising, these data are limited to a rodent cell line and human muscle biopsy studies are needed to validate and elucidate the significance of these findings.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33287129","pmcid":"PMC7761648","openalex_id":null,"authors":[],"funders":[{"funder_name":"JUVN3 Holdings","grant_id":"N/A","title":null}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":null,"license":"https://creativecommons.org/licenses/by/4.0/","oa_locations":[{"url":"https://www.mdpi.com/2072-6643/12/12/3727/pdf","host_type":"publisher"},{"url":"https://europepmc.org/articles/PMC7761648","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7761648?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Animals","Biomarkers","Cytokines","Humans","Mitochondria","Muscles","Myoblasts","NAD","Nicotinamide Phosphoribosyltransferase","RNA, Messenger","Rodentia","Sirtuin 1","Sirtuins","Uric Acid"],"mesh_terms":["Muscles","Mitochondria","Myoblasts","Animals","Humans","Rodentia","Uric Acid","NAD","Sirtuins","RNA, Messenger","Cytokines","Nicotinamide Phosphoribosyltransferase","Sirtuin 1","Biomarkers"],"keywords":["Mitochondria","Sirtuins","Mrnas","Theacrine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T20:29:38.832920Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}