Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study
Abstract Context Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases. Objective We evaluated the safety and physiologic effects of NAD augmentation by administering its precursor, β-nicotinamide mo...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2023-08, Vol.108 (8), p.1968-1980 |
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| container_end_page | 1980 |
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| container_issue | 8 |
| container_start_page | 1968 |
| container_title | The journal of clinical endocrinology and metabolism |
| container_volume | 108 |
| creator | Pencina, Karol Mateusz Valderrabano, Rodrigo Wipper, Benjamin Orkaby, Ariela R Reid, Kieran F Storer, Thomas Lin, Alexander P Merugumala, Sai Wilson, Lauren Latham, Nancy Ghattas-Puylara, Catherine Ozimek, Noelle E Cheng, Ming Bhargava, Avantika Memish-Beleva, Yusnie Lawney, Brian Lavu, Siva Swain, Pamela M Apte, Rajendra S Sinclair, David A Livingston, David Bhasin, Shalender |
| description | Abstract
Context
Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases.
Objective
We evaluated the safety and physiologic effects of NAD augmentation by administering its precursor, β-nicotinamide mononucleotide (MIB-626, Metro International Biotech, Worcester, MA), in adults at risk for age-related conditions.
Methods
Thirty overweight or obese adults, ≥ 45 years, were randomized in a 2:1 ratio to 2 MIB-626 tablets each containing 500 mg of microcrystalline β-nicotinamide mononucleotide or placebo twice daily for 28 days. Study outcomes included safety; NAD and its metabolome; body weight; liver, muscle, and intra-abdominal fat; insulin sensitivity; blood pressure; lipids; physical performance, and muscle bioenergetics.
Results
Adverse events were similar between groups. MIB-626 treatment substantially increased circulating concentrations of NAD and its metabolites. Body weight (difference −1.9 [−3.3, −0.5] kg, P = .008); diastolic blood pressure (difference −7.01 [−13.44, −0.59] mmHg, P = .034); total cholesterol (difference −26.89 [−44.34, −9.44] mg/dL, P = .004), low-density lipoprotein (LDL) cholesterol (−18.73 [−31.85, −5.60] mg/dL, P = .007), and nonhigh-density lipoprotein cholesterol decreased significantly more in the MIB-626 group than placebo. Changes in muscle strength, muscle fatigability, aerobic capacity, and stair-climbing power did not differ significantly between groups. Insulin sensitivity and hepatic and intra-abdominal fat did not change in either group.
Conclusions
MIB-626 administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure. These data provide the rationale for larger trials to assess the efficacy of NAD augmentation in improving cardiometabolic outcomes in older adults. |
| doi_str_mv | 10.1210/clinem/dgad027 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11491622</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A776056145</galeid><oup_id>10.1210/clinem/dgad027</oup_id><sourcerecordid>A776056145</sourcerecordid><originalsourceid>FETCH-LOGICAL-c480t-d4d4e1b85ecb6ebaa5767ac363f8254fb7956ddf0c86fd49218b182f7f24b3d3</originalsourceid><addsrcrecordid>eNqFkk1v3CAQhq2qVbNJe-2xQuqlPTgBjMHupVqln1LardQcekMYxl4iDBuwE-2_D6vdph-KVHFAmnnnGWZ4i-IFwaeEEnymnfUwnplBGUzFo2JBWlaXgrTicbHAmJKyFfTnUXGc0hXGhLG6elocVVww3NZsUdx-szpM1qvRGkBLAz7z0HvrZ-0gJ3bBeRjBT2qywSPr0eoG4i3YYT2hENGqgwToqzXGQbkcwCDlDVo5AzHjZjelt2iJvq-3yQYXBqvRj2k222fFk165BM8P90lx-fHD5fnn8mL16cv58qLUrMFTaZhhQLqmBt1x6JSqBRdKV7zqG1qzvhNtzY3psW54b1hLSdORhvaip6yrTHVSvNtjN3M3gtF5jqic3EQ7qriVQVn5d8bbtRzCjSSEtYRTmgmvD4QYrmdIkxxt0uCc8hDmJKkQVV4353WWvvpHehXm6PN4ssI1EfnFov2tGpQDaX0fcmO9g8qlEBzXnLAd6_QBVT4GxvxjHnqb4w8V6BhSitDfD0mw3FlF7q0iD1bJBS__XM29_Jc3suDNXhDmzf9gd3WnyuU</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3051782579</pqid></control><display><type>article</type><title>Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Pencina, Karol Mateusz ; Valderrabano, Rodrigo ; Wipper, Benjamin ; Orkaby, Ariela R ; Reid, Kieran F ; Storer, Thomas ; Lin, Alexander P ; Merugumala, Sai ; Wilson, Lauren ; Latham, Nancy ; Ghattas-Puylara, Catherine ; Ozimek, Noelle E ; Cheng, Ming ; Bhargava, Avantika ; Memish-Beleva, Yusnie ; Lawney, Brian ; Lavu, Siva ; Swain, Pamela M ; Apte, Rajendra S ; Sinclair, David A ; Livingston, David ; Bhasin, Shalender</creator><creatorcontrib>Pencina, Karol Mateusz ; Valderrabano, Rodrigo ; Wipper, Benjamin ; Orkaby, Ariela R ; Reid, Kieran F ; Storer, Thomas ; Lin, Alexander P ; Merugumala, Sai ; Wilson, Lauren ; Latham, Nancy ; Ghattas-Puylara, Catherine ; Ozimek, Noelle E ; Cheng, Ming ; Bhargava, Avantika ; Memish-Beleva, Yusnie ; Lawney, Brian ; Lavu, Siva ; Swain, Pamela M ; Apte, Rajendra S ; Sinclair, David A ; Livingston, David ; Bhasin, Shalender</creatorcontrib><description>Abstract
Context
Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases.
Objective
We evaluated the safety and physiologic effects of NAD augmentation by administering its precursor, β-nicotinamide mononucleotide (MIB-626, Metro International Biotech, Worcester, MA), in adults at risk for age-related conditions.
Methods
Thirty overweight or obese adults, ≥ 45 years, were randomized in a 2:1 ratio to 2 MIB-626 tablets each containing 500 mg of microcrystalline β-nicotinamide mononucleotide or placebo twice daily for 28 days. Study outcomes included safety; NAD and its metabolome; body weight; liver, muscle, and intra-abdominal fat; insulin sensitivity; blood pressure; lipids; physical performance, and muscle bioenergetics.
Results
Adverse events were similar between groups. MIB-626 treatment substantially increased circulating concentrations of NAD and its metabolites. Body weight (difference −1.9 [−3.3, −0.5] kg, P = .008); diastolic blood pressure (difference −7.01 [−13.44, −0.59] mmHg, P = .034); total cholesterol (difference −26.89 [−44.34, −9.44] mg/dL, P = .004), low-density lipoprotein (LDL) cholesterol (−18.73 [−31.85, −5.60] mg/dL, P = .007), and nonhigh-density lipoprotein cholesterol decreased significantly more in the MIB-626 group than placebo. Changes in muscle strength, muscle fatigability, aerobic capacity, and stair-climbing power did not differ significantly between groups. Insulin sensitivity and hepatic and intra-abdominal fat did not change in either group.
Conclusions
MIB-626 administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure. These data provide the rationale for larger trials to assess the efficacy of NAD augmentation in improving cardiometabolic outcomes in older adults.</description><identifier>ISSN: 0021-972X</identifier><identifier>ISSN: 1945-7197</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/clinem/dgad027</identifier><identifier>PMID: 36740954</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>2-Methylisoborneol ; Aerobic capacity ; Aged ; Aging ; Bioenergetics ; Blood cholesterol ; Blood pressure ; Body Weight ; Cholesterol ; Clinical ; High density lipoprotein ; Humans ; Insulin ; Insulin Resistance ; Lipids ; Liver ; Low density lipoprotein ; Low density lipoproteins ; Metabolites ; Middle age ; Middle Aged ; Muscle strength ; NAD ; NAD - metabolism ; NAD - therapeutic use ; Niacinamide ; Nicotinamide Mononucleotide - therapeutic use ; Obesity ; Older people ; Overweight ; Placebos ; Purines</subject><ispartof>The journal of clinical endocrinology and metabolism, 2023-08, Vol.108 (8), p.1968-1980</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2023 Oxford University Press</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c480t-d4d4e1b85ecb6ebaa5767ac363f8254fb7956ddf0c86fd49218b182f7f24b3d3</citedby><cites>FETCH-LOGICAL-c480t-d4d4e1b85ecb6ebaa5767ac363f8254fb7956ddf0c86fd49218b182f7f24b3d3</cites><orcidid>0000-0003-4359-5131</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36740954$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pencina, Karol Mateusz</creatorcontrib><creatorcontrib>Valderrabano, Rodrigo</creatorcontrib><creatorcontrib>Wipper, Benjamin</creatorcontrib><creatorcontrib>Orkaby, Ariela R</creatorcontrib><creatorcontrib>Reid, Kieran F</creatorcontrib><creatorcontrib>Storer, Thomas</creatorcontrib><creatorcontrib>Lin, Alexander P</creatorcontrib><creatorcontrib>Merugumala, Sai</creatorcontrib><creatorcontrib>Wilson, Lauren</creatorcontrib><creatorcontrib>Latham, Nancy</creatorcontrib><creatorcontrib>Ghattas-Puylara, Catherine</creatorcontrib><creatorcontrib>Ozimek, Noelle E</creatorcontrib><creatorcontrib>Cheng, Ming</creatorcontrib><creatorcontrib>Bhargava, Avantika</creatorcontrib><creatorcontrib>Memish-Beleva, Yusnie</creatorcontrib><creatorcontrib>Lawney, Brian</creatorcontrib><creatorcontrib>Lavu, Siva</creatorcontrib><creatorcontrib>Swain, Pamela M</creatorcontrib><creatorcontrib>Apte, Rajendra S</creatorcontrib><creatorcontrib>Sinclair, David A</creatorcontrib><creatorcontrib>Livingston, David</creatorcontrib><creatorcontrib>Bhasin, Shalender</creatorcontrib><title>Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Abstract
Context
Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases.
Objective
We evaluated the safety and physiologic effects of NAD augmentation by administering its precursor, β-nicotinamide mononucleotide (MIB-626, Metro International Biotech, Worcester, MA), in adults at risk for age-related conditions.
Methods
Thirty overweight or obese adults, ≥ 45 years, were randomized in a 2:1 ratio to 2 MIB-626 tablets each containing 500 mg of microcrystalline β-nicotinamide mononucleotide or placebo twice daily for 28 days. Study outcomes included safety; NAD and its metabolome; body weight; liver, muscle, and intra-abdominal fat; insulin sensitivity; blood pressure; lipids; physical performance, and muscle bioenergetics.
Results
Adverse events were similar between groups. MIB-626 treatment substantially increased circulating concentrations of NAD and its metabolites. Body weight (difference −1.9 [−3.3, −0.5] kg, P = .008); diastolic blood pressure (difference −7.01 [−13.44, −0.59] mmHg, P = .034); total cholesterol (difference −26.89 [−44.34, −9.44] mg/dL, P = .004), low-density lipoprotein (LDL) cholesterol (−18.73 [−31.85, −5.60] mg/dL, P = .007), and nonhigh-density lipoprotein cholesterol decreased significantly more in the MIB-626 group than placebo. Changes in muscle strength, muscle fatigability, aerobic capacity, and stair-climbing power did not differ significantly between groups. Insulin sensitivity and hepatic and intra-abdominal fat did not change in either group.
Conclusions
MIB-626 administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure. These data provide the rationale for larger trials to assess the efficacy of NAD augmentation in improving cardiometabolic outcomes in older adults.</description><subject>2-Methylisoborneol</subject><subject>Aerobic capacity</subject><subject>Aged</subject><subject>Aging</subject><subject>Bioenergetics</subject><subject>Blood cholesterol</subject><subject>Blood pressure</subject><subject>Body Weight</subject><subject>Cholesterol</subject><subject>Clinical</subject><subject>High density lipoprotein</subject><subject>Humans</subject><subject>Insulin</subject><subject>Insulin Resistance</subject><subject>Lipids</subject><subject>Liver</subject><subject>Low density lipoprotein</subject><subject>Low density lipoproteins</subject><subject>Metabolites</subject><subject>Middle age</subject><subject>Middle Aged</subject><subject>Muscle strength</subject><subject>NAD</subject><subject>NAD - metabolism</subject><subject>NAD - therapeutic use</subject><subject>Niacinamide</subject><subject>Nicotinamide Mononucleotide - therapeutic use</subject><subject>Obesity</subject><subject>Older people</subject><subject>Overweight</subject><subject>Placebos</subject><subject>Purines</subject><issn>0021-972X</issn><issn>1945-7197</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1v3CAQhq2qVbNJe-2xQuqlPTgBjMHupVqln1LardQcekMYxl4iDBuwE-2_D6vdph-KVHFAmnnnGWZ4i-IFwaeEEnymnfUwnplBGUzFo2JBWlaXgrTicbHAmJKyFfTnUXGc0hXGhLG6elocVVww3NZsUdx-szpM1qvRGkBLAz7z0HvrZ-0gJ3bBeRjBT2qywSPr0eoG4i3YYT2hENGqgwToqzXGQbkcwCDlDVo5AzHjZjelt2iJvq-3yQYXBqvRj2k222fFk165BM8P90lx-fHD5fnn8mL16cv58qLUrMFTaZhhQLqmBt1x6JSqBRdKV7zqG1qzvhNtzY3psW54b1hLSdORhvaip6yrTHVSvNtjN3M3gtF5jqic3EQ7qriVQVn5d8bbtRzCjSSEtYRTmgmvD4QYrmdIkxxt0uCc8hDmJKkQVV4353WWvvpHehXm6PN4ssI1EfnFov2tGpQDaX0fcmO9g8qlEBzXnLAd6_QBVT4GxvxjHnqb4w8V6BhSitDfD0mw3FlF7q0iD1bJBS__XM29_Jc3suDNXhDmzf9gd3WnyuU</recordid><startdate>20230801</startdate><enddate>20230801</enddate><creator>Pencina, Karol Mateusz</creator><creator>Valderrabano, Rodrigo</creator><creator>Wipper, Benjamin</creator><creator>Orkaby, Ariela R</creator><creator>Reid, Kieran F</creator><creator>Storer, Thomas</creator><creator>Lin, Alexander P</creator><creator>Merugumala, Sai</creator><creator>Wilson, Lauren</creator><creator>Latham, Nancy</creator><creator>Ghattas-Puylara, Catherine</creator><creator>Ozimek, Noelle E</creator><creator>Cheng, Ming</creator><creator>Bhargava, Avantika</creator><creator>Memish-Beleva, Yusnie</creator><creator>Lawney, Brian</creator><creator>Lavu, Siva</creator><creator>Swain, Pamela M</creator><creator>Apte, Rajendra S</creator><creator>Sinclair, David A</creator><creator>Livingston, David</creator><creator>Bhasin, Shalender</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4359-5131</orcidid></search><sort><creationdate>20230801</creationdate><title>Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study</title><author>Pencina, Karol Mateusz ; Valderrabano, Rodrigo ; Wipper, Benjamin ; Orkaby, Ariela R ; Reid, Kieran F ; Storer, Thomas ; Lin, Alexander P ; Merugumala, Sai ; Wilson, Lauren ; Latham, Nancy ; Ghattas-Puylara, Catherine ; Ozimek, Noelle E ; Cheng, Ming ; Bhargava, Avantika ; Memish-Beleva, Yusnie ; Lawney, Brian ; Lavu, Siva ; Swain, Pamela M ; Apte, Rajendra S ; Sinclair, David A ; Livingston, David ; Bhasin, Shalender</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c480t-d4d4e1b85ecb6ebaa5767ac363f8254fb7956ddf0c86fd49218b182f7f24b3d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>2-Methylisoborneol</topic><topic>Aerobic capacity</topic><topic>Aged</topic><topic>Aging</topic><topic>Bioenergetics</topic><topic>Blood cholesterol</topic><topic>Blood pressure</topic><topic>Body Weight</topic><topic>Cholesterol</topic><topic>Clinical</topic><topic>High density lipoprotein</topic><topic>Humans</topic><topic>Insulin</topic><topic>Insulin Resistance</topic><topic>Lipids</topic><topic>Liver</topic><topic>Low density lipoprotein</topic><topic>Low density lipoproteins</topic><topic>Metabolites</topic><topic>Middle age</topic><topic>Middle Aged</topic><topic>Muscle strength</topic><topic>NAD</topic><topic>NAD - metabolism</topic><topic>NAD - therapeutic use</topic><topic>Niacinamide</topic><topic>Nicotinamide Mononucleotide - therapeutic use</topic><topic>Obesity</topic><topic>Older people</topic><topic>Overweight</topic><topic>Placebos</topic><topic>Purines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pencina, Karol Mateusz</creatorcontrib><creatorcontrib>Valderrabano, Rodrigo</creatorcontrib><creatorcontrib>Wipper, Benjamin</creatorcontrib><creatorcontrib>Orkaby, Ariela R</creatorcontrib><creatorcontrib>Reid, Kieran F</creatorcontrib><creatorcontrib>Storer, Thomas</creatorcontrib><creatorcontrib>Lin, Alexander P</creatorcontrib><creatorcontrib>Merugumala, Sai</creatorcontrib><creatorcontrib>Wilson, Lauren</creatorcontrib><creatorcontrib>Latham, Nancy</creatorcontrib><creatorcontrib>Ghattas-Puylara, Catherine</creatorcontrib><creatorcontrib>Ozimek, Noelle E</creatorcontrib><creatorcontrib>Cheng, Ming</creatorcontrib><creatorcontrib>Bhargava, Avantika</creatorcontrib><creatorcontrib>Memish-Beleva, Yusnie</creatorcontrib><creatorcontrib>Lawney, Brian</creatorcontrib><creatorcontrib>Lavu, Siva</creatorcontrib><creatorcontrib>Swain, Pamela M</creatorcontrib><creatorcontrib>Apte, Rajendra S</creatorcontrib><creatorcontrib>Sinclair, David A</creatorcontrib><creatorcontrib>Livingston, David</creatorcontrib><creatorcontrib>Bhasin, Shalender</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pencina, Karol Mateusz</au><au>Valderrabano, Rodrigo</au><au>Wipper, Benjamin</au><au>Orkaby, Ariela R</au><au>Reid, Kieran F</au><au>Storer, Thomas</au><au>Lin, Alexander P</au><au>Merugumala, Sai</au><au>Wilson, Lauren</au><au>Latham, Nancy</au><au>Ghattas-Puylara, Catherine</au><au>Ozimek, Noelle E</au><au>Cheng, Ming</au><au>Bhargava, Avantika</au><au>Memish-Beleva, Yusnie</au><au>Lawney, Brian</au><au>Lavu, Siva</au><au>Swain, Pamela M</au><au>Apte, Rajendra S</au><au>Sinclair, David A</au><au>Livingston, David</au><au>Bhasin, Shalender</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2023-08-01</date><risdate>2023</risdate><volume>108</volume><issue>8</issue><spage>1968</spage><epage>1980</epage><pages>1968-1980</pages><issn>0021-972X</issn><issn>1945-7197</issn><eissn>1945-7197</eissn><abstract>Abstract
Context
Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases.
Objective
We evaluated the safety and physiologic effects of NAD augmentation by administering its precursor, β-nicotinamide mononucleotide (MIB-626, Metro International Biotech, Worcester, MA), in adults at risk for age-related conditions.
Methods
Thirty overweight or obese adults, ≥ 45 years, were randomized in a 2:1 ratio to 2 MIB-626 tablets each containing 500 mg of microcrystalline β-nicotinamide mononucleotide or placebo twice daily for 28 days. Study outcomes included safety; NAD and its metabolome; body weight; liver, muscle, and intra-abdominal fat; insulin sensitivity; blood pressure; lipids; physical performance, and muscle bioenergetics.
Results
Adverse events were similar between groups. MIB-626 treatment substantially increased circulating concentrations of NAD and its metabolites. Body weight (difference −1.9 [−3.3, −0.5] kg, P = .008); diastolic blood pressure (difference −7.01 [−13.44, −0.59] mmHg, P = .034); total cholesterol (difference −26.89 [−44.34, −9.44] mg/dL, P = .004), low-density lipoprotein (LDL) cholesterol (−18.73 [−31.85, −5.60] mg/dL, P = .007), and nonhigh-density lipoprotein cholesterol decreased significantly more in the MIB-626 group than placebo. Changes in muscle strength, muscle fatigability, aerobic capacity, and stair-climbing power did not differ significantly between groups. Insulin sensitivity and hepatic and intra-abdominal fat did not change in either group.
Conclusions
MIB-626 administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure. These data provide the rationale for larger trials to assess the efficacy of NAD augmentation in improving cardiometabolic outcomes in older adults.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>36740954</pmid><doi>10.1210/clinem/dgad027</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-4359-5131</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-972X |
| ispartof | The journal of clinical endocrinology and metabolism, 2023-08, Vol.108 (8), p.1968-1980 |
| issn | 0021-972X 1945-7197 1945-7197 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11491622 |
| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | 2-Methylisoborneol Aerobic capacity Aged Aging Bioenergetics Blood cholesterol Blood pressure Body Weight Cholesterol Clinical High density lipoprotein Humans Insulin Insulin Resistance Lipids Liver Low density lipoprotein Low density lipoproteins Metabolites Middle age Middle Aged Muscle strength NAD NAD - metabolism NAD - therapeutic use Niacinamide Nicotinamide Mononucleotide - therapeutic use Obesity Older people Overweight Placebos Purines |
| title | Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T08%3A16%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Nicotinamide%20Adenine%20Dinucleotide%20Augmentation%20in%20Overweight%20or%20Obese%20Middle-Aged%20and%20Older%20Adults:%20A%20Physiologic%20Study&rft.jtitle=The%20journal%20of%20clinical%20endocrinology%20and%20metabolism&rft.au=Pencina,%20Karol%20Mateusz&rft.date=2023-08-01&rft.volume=108&rft.issue=8&rft.spage=1968&rft.epage=1980&rft.pages=1968-1980&rft.issn=0021-972X&rft.eissn=1945-7197&rft_id=info:doi/10.1210/clinem/dgad027&rft_dat=%3Cgale_pubme%3EA776056145%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3051782579&rft_id=info:pmid/36740954&rft_galeid=A776056145&rft_oup_id=10.1210/clinem/dgad027&rfr_iscdi=true |