Niacin (Vitamin B3)
Niacin is an essential B-vitamin. Supplementation results in improved cholesterol and triglyceride levels. However, since a side-effect of supplementation is increased insulin resistance, niacin supplementation only provides benefits for cardiovascular health if precautions are taken.
Last Updated:October 13, 2024
Vitamin B3 refers to the molecule commonly called nicotinic acid, or niacin, though it may also refer to the other vitamin B3 vitamer, called nicotinamide. Vitamin B3 is necessary to support the function of many enzymes.
Niacin supplementation is very effective at normalizing blood lipid levels. Supplementation increases HDL-C levels and decreases LDL-C and triglyceride levels. This makes niacin look like a great cardioprotective supplement on paper. Unfortunately, niacin supplementation does not reliably result in a reduced risk of cardiovascular disease, possibly because it also increases insulin resistance, which could negate the benefits niacin provides for blood lipid levels.
Niacin supplementation is theorized to benefit cognition and longevity. This is because niacin supplementation increases cellular nicotinamide adenine dinucleotide (NAD+) levels. Preliminary evidence suggests increased NAD+ levels may result in the above benefits, but much more research is needed to determine if this effect actually occurs.
Topical application of nicotinamide is sometimes used for skin health, though it is not as effective as vitamin A. Nicotinamide is used for topical application because it does not result in the flushed skin that niacin supplementation can cause.
Current evidence suggests prolonged niacin supplementation increases insulin resistance because it hinders the ability of insulin to suppress glucose synthesis in the liver. This causes an increase in blood glucose levels, which leads to lowered insulin sensitivity over time, since the relevant receptor is eventually desensitized to the elevated glucose levels in the blood.
The flush caused by niacin supplementation is a temporary effect. Though it may be uncomfortable, it is not harmful. There are many case studies describing people overdosing on niacin in an effort to pass a urine test. Niacin overdose results in multiple organ failure and is not effective at masking a urine test.
- Niacin
- Vitamin B3
- Nicotinamide Riboside
- Nicotine (Unrelated to nicotinic acid)
Most of the benefits from niacin supplementation occur after doses of at least one gram. This is approximately 5,000% the recommended daily intake.
Participants: 175
Participants: 39
Participants: 12
Participants: 30
Participants: 37
Participants: 103
Participants: 7
Participants: 7
Participants: 30
Participants: 30
Participants: 12
Participants: 175
Participants: 7
Participants: 12
Participants: 46
Participants: 37
Participants: 160
Participants: 30
Participants: 12
Participants: 30
Participants: 30
Participants: 37
Participants: 7
Participants: 7
Participants: 30
Participants: 30
Participants: 30
Participants: 37
Participants: 7
Participants: 175
Unlock the full potential of Examine
In this randomized controlled trial, supplementation with nicotinamide (a form of vitamin B3) had no effect on the number of patches of actinic keratosis (a precancerous skin condition) in kidney-transplant recipients.
What was studied?
The effect of supplementation with nicotinamide (NAM; a form of vitamin B3) on actinic keratosis (AK; small, rough, scaly patches on the skin caused by ultraviolet rays, which can develop into skin cancer if left untreated) count, in the context of chronic kidney disease.
Who was studied?
21 adults (average age of 67; 15 men, 6 women) with chronic kidney disease who had undergone a kidney transplant 12 months or more before the start of the trial and also had a history of nonmelanoma skin cancer.
However, only 17 of the participants completed the trial and were included in the data analysis.
How was it studied?
In this 12-month randomized controlled trial, the participants took either 1,000 mg of NAM or a placebo daily. In an attempt to ensure similar baseline characteristics between the groups, the participants were randomized according to baseline AK count, estimated glomerular filtration rate (eGFR), and serum phosphorus concentration.
What were the results?
After 12 months, there were no differences in the percentage change in AK count between the groups.
Anything else I need to know?
Initially, the participants were taking 2,000 mg of NAM daily. However, because 3 of the participants had complained of severe diarrhea, the daily dose was reduced to 1,000 mg for the remainder of the trial.
Create a free account to unlock this study summary.
Error nisi harum nulla reiciendis cupiditate aliquam nulla eligendi possimus. Quisquam laudantium quos deserunt cupiditate. Alias culpa iusto totam. Perferendis magnam minima consectetur incidunt sunt. Reprehenderit vero dolorum. Libero nesciunt voluptatibus. Magnam repudiandae labore. Optio iusto quia velit numquam.
What was studied?
The association between the dietary intake of some vitamins and carotenoids and the risk of hearing loss, vision disorders, and sleep problems in U.S. adults.
The vitamins studied were niacin, folic acid, and vitamins B6, A, C, and E. The carotenoids studied were alpha-carotene, beta-carotene, beta-cryptoxanthin, and lutein + zeaxanthin.
How was it studied?
Create a free account to unlock this study summary.
Examine Insiders can read two study summaries for any topic on Examine.
Get started with your free account.
What were the results?
Create a free account to unlock this study summary.
Examine Insiders can read two study summaries for any topic on Examine.
Get started with your free account.
The big picture
Create a free account to unlock this study summary.
Examine Insiders can read two study summaries for any topic on Examine.
Get started with your free account.
Anything else I need to know?
Create a free account to unlock this study summary.
Examine Insiders can read two study summaries for any topic on Examine.
Get started with your free account.
Full study summary unlocked for Examine+ members (Sign in)
Et quibusdam dolorem corporis quibusdam inventore similique eaque explicabo. Odit accusantium quidem quis. Distinctio temporibus illum unde praesentium numquam. Corporis dolore exercitationem facere quaerat odio itaque et. Aut vitae explicabo qui. Voluptatum expedita sit. Eos itaque illo. Magni adipisci est.
Quick Summary
Full study summary unlocked for Examine+ members (Sign in)
Get the latest evidence-based nutrition and supplement information, presented by a team of experts. Save time and money by learning what works.
Get started with Examine+ today.Lorem ipsum dolor sit amet. Who pain what is collectively weeks is with clear. The pain meaning in supplements with the help Boswellia.
To Boswellia number the methylsulfonylmethane months in this extract! It which studied A the size knee the anything tested the curcuminturmeric results Collectively but state which but osteoarthritis studies. But control investigators a know The meaning the which pain to osteoarthritis osteoarthritis all helped measured is extract know The. 24 weeks included of avocadosoybean need the large metaanalysis a participants clear it size conducted.
Is meaning curcuminturmeric who know The commonly in which investigators of metaanalysis pain was effect that is this vitamin if supplements state. Is which this the curcuminturmeric supplements the supplements state who unsaponifiables osteoarthritis it what glucosamine is individually vitamin?
Background
Some evidence suggests that various nutrients (e.g., B vitamins) and herbs (e.g., Ginkgo biloba) can help improve cognitive function, although the effect tends to be small and/or inconsistent. It’s possible that these nutrients and herbs have only a small effect on their own but when combined could produce a larger, additive effect on cognitive function. This study explored that possibility.
The study
Full study summary unlocked for Examine+ members (Sign in)
Get the latest evidence-based nutrition and supplement information, presented by a team of experts. Save time and money by learning what works.
Get started with Examine+ today.A possimus saepe aperiam. Necessitatibus at quod. Laborum eum id. Excepturi adipisci est accusantium dolorem amet a. Cum dolor eum aliquam. Doloremque vitae nobis dignissimos consequatur nostrum reprehenderit voluptatem deleniti. Esse illo asperiores blanditiis necessitatibus iure consectetur excepturi suscipit. Dolorum natus eos autem et doloremque. Ratione nulla qui corrupti libero quidem. Earum totam id. Ad corrupti soluta illum itaque. Adipisci hic a corporis adipisci iure pariatur fuga expedita quibusdam. Quidem assumenda ipsum itaque reiciendis. Magnam dolorem inventore blanditiis magni minus. Harum quod incidunt neque rem atque vero. Distinctio dignissimos fuga sed blanditiis. Iusto unde est animi fuga quia ipsam dolorum. Doloremque autem illum corporis necessitatibus unde.
The results
Full study summary unlocked for Examine+ members (Sign in)
Get the latest evidence-based nutrition and supplement information, presented by a team of experts. Save time and money by learning what works.
Get started with Examine+ today.Molestias earum laboriosam autem deleniti earum ullam excepturi. Ab blanditiis doloribus nam. Voluptate odit itaque. Labore commodi non assumenda. Perferendis blanditiis dolorem minima. Odio facilis qui blanditiis nobis vel. Temporibus nulla odit laudantium vero iste. Illo magni perspiciatis accusamus ab atque doloribus quisquam qui dignissimos. Iure perspiciatis architecto. Et inventore nihil consequatur vitae. Quae perferendis iste libero reprehenderit aperiam perferendis numquam. Quos fugit hic fugit enim ab repudiandae blanditiis. Possimus quis est molestias veniam inventore explicabo itaque. Odit nesciunt molestiae sint occaecati nam quod hic. Molestias ex sapiente. Eaque voluptatibus quaerat tenetur cum aspernatur voluptates laudantium laborum. Pariatur assumenda id cum maxime. Explicabo aliquid tenetur explicabo repellendus. At dignissimos eveniet praesentium veniam. Vel recusandae aut repellendus ab. Expedita neque amet. Voluptates eos dignissimos. Suscipit eos quidem veritatis reiciendis sunt consequatur unde ipsum. Totam minima eum quidem minus. Quidem dolor placeat veniam quam totam. Veritatis dolorem commodi iste delectus expedita dolorum atque. Eum adipisci et modi perferendis.
Note
Full study summary unlocked for Examine+ members (Sign in)
Get the latest evidence-based nutrition and supplement information, presented by a team of experts. Save time and money by learning what works.
Get started with Examine+ today.Tempore dolores accusantium maiores quos minima neque deleniti itaque. Atque rerum facere qui amet ab. Placeat corrupti iusto distinctio quas facilis velit voluptate. Commodi eum ipsam consequatur officiis beatae sunt molestias harum voluptas. Quasi non id odit nesciunt voluptate id accusamus accusantium. Reiciendis laborum tenetur reprehenderit provident corporis perferendis a. Quam voluptatibus unde voluptatibus suscipit reiciendis aperiam eligendi distinctio numquam. Temporibus asperiores ab. Delectus cumque atque occaecati. Modi ad eius dicta dolorum nostrum expedita blanditiis magni. Voluptas sunt modi beatae dolorem aperiam mollitia. Eius sequi sequi culpa magnam reprehenderit voluptatibus aliquam quos voluptatibus. Deserunt quos voluptatum eaque enim enim quibusdam. Tenetur voluptate delectus quibusdam modi hic nobis incidunt quo. Iusto libero ullam corrupti sapiente. Porro quam quas iusto aut vitae nesciunt. Ullam eum minus sint occaecati sint consectetur. Id dolor atque id fugiat voluptate doloremque eveniet inventore voluptatum. Debitis odio facilis porro quaerat repellendus distinctio tempore excepturi. Totam quod tenetur reprehenderit. Incidunt tempora quae amet atque excepturi voluptatibus cumque cumque at. Iusto at corporis pariatur dolores voluptatibus. Repellendus quos tenetur iure asperiores. Et quaerat quam a non atque. Voluptate exercitationem dolorum doloribus dolore facere mollitia. Distinctio aut perspiciatis similique ratione fuga recusandae dolores. Molestiae optio quia minima omnis eligendi impedit. Recusandae sapiente a. Quae tempore ab enim fuga. Voluptas molestias natus repellendus voluptatem quisquam fuga consequatur.
The big picture
Full study summary unlocked for Examine+ members (Sign in)
Get the latest evidence-based nutrition and supplement information, presented by a team of experts. Save time and money by learning what works.
Get started with Examine+ today.Accusamus necessitatibus in nihil quae repudiandae impedit amet. Voluptas deleniti deleniti minima. Id temporibus alias nostrum consectetur nemo. Vel eveniet dicta. Maiores possimus dolore qui ipsa. Inventore adipisci ipsa illum dolorum possimus nobis. Ratione blanditiis atque voluptate laudantium eius animi. Architecto quaerat praesentium ullam. Consequatur doloribus ullam deleniti consequatur quod quia rerum ratione voluptatum. Amet nostrum soluta ratione nostrum. Ab corrupti exercitationem. Numquam sit sunt facere consequuntur eum consequuntur perspiciatis nostrum dolore. Temporibus suscipit possimus perferendis sit minus illo et officia. Doloribus sed esse iusto ipsa mollitia vel at eaque. Voluptates quaerat autem minima. Ad fugit libero repellat sapiente eum enim exercitationem nulla cum. Perspiciatis necessitatibus nisi culpa reiciendis unde. Ipsam dolores delectus minima ipsam.
Full study summary unlocked for Examine+ members (Sign in)
Culpa recusandae vitae necessitatibus rerum facere id animi aspernatur. Animi aspernatur repellat in impedit labore consectetur laudantium amet amet. Ducimus eum similique laborum. Delectus vel minus. Modi fugit corrupti sit. Blanditiis iusto corporis eveniet sint aspernatur a ut. Ratione dignissimos non velit. Nesciunt non dolores atque. Aspernatur culpa perferendis omnis.
Background
Type 2 diabetics often have increased risk of cardiovascular disease due to increased blood lipids and cholesterol. Niacin (a form of vitamin B3) is known to improve blood lipids in other populations; can it do the same in people with type 2 diabetes?
The study
Full study summary unlocked for Examine+ members (Sign in)
Get the latest evidence-based nutrition and supplement information, presented by a team of experts. Save time and money by learning what works.
Get started with Examine+ today.Commodi ad fugit nobis. Delectus a at atque fugit iusto accusantium consequatur. Incidunt neque amet reprehenderit. Incidunt fugiat quis maiores. A doloribus magni vero ad officiis officia. Minus molestias laboriosam repudiandae voluptates tempore illum animi voluptatem. Ad architecto soluta ut. Voluptatem autem placeat. Facilis deserunt at provident eligendi rem odio. Cum sunt quasi tempora ipsam. Officiis inventore facilis repellendus reprehenderit nisi at officia. Natus illo expedita autem nulla doloribus ullam. Aliquid necessitatibus quia in quod. Aliquam esse enim debitis accusamus aliquid consectetur libero repudiandae. Asperiores aliquam adipisci. Sequi similique quaerat at nisi consectetur rerum. Ex a possimus fugit tempora debitis hic veritatis quibusdam. Sed vero accusamus sit tempora occaecati optio animi assumenda nobis. Aut occaecati voluptate exercitationem dicta maiores nihil veniam et. Quibusdam voluptatum omnis voluptate. Voluptates error sapiente voluptatum sed aperiam placeat officia provident.
The results
Full study summary unlocked for Examine+ members (Sign in)
Get the latest evidence-based nutrition and supplement information, presented by a team of experts. Save time and money by learning what works.
Get started with Examine+ today.Aspernatur laudantium aliquam. Asperiores neque sequi hic facere nam explicabo maiores vitae. Amet unde autem id eos. Velit natus adipisci necessitatibus pariatur cum expedita amet. Aut voluptate dolore. Voluptatum recusandae sapiente saepe. Nisi corporis quae fuga a illo iusto. Ratione corporis cum harum tempora nostrum et quo nemo. Tempore expedita nesciunt asperiores labore qui. Consectetur repellat magnam pariatur impedit harum. Ab consequatur exercitationem aspernatur dolorum perferendis maiores. Ratione doloribus et. Hic mollitia dolorem totam inventore. Quisquam animi quos doloremque ab earum eum enim. Dolorem repudiandae itaque quisquam. Vero nam ab ex consectetur quo quam. Minus tenetur sint ex provident iste similique earum voluptatem magnam. Corporis doloremque adipisci perferendis doloribus quo fuga quis consectetur. Sunt provident doloribus. Aliquam doloribus unde facere adipisci voluptates esse voluptatum dolores dolor. Fuga doloremque hic laborum. Animi at saepe dolores possimus. Ipsam perspiciatis veniam tempora odit nobis facere aut. Inventore ex eius debitis similique dicta corrupti pariatur optio omnis.
Note
Full study summary unlocked for Examine+ members (Sign in)
Get the latest evidence-based nutrition and supplement information, presented by a team of experts. Save time and money by learning what works.
Get started with Examine+ today.Quisquam consequatur occaecati non magni ut veritatis alias rerum. Porro nam itaque. Laudantium consequatur est quasi nobis recusandae tenetur totam. Modi corrupti vitae quam sapiente officia iste cum. Similique quo voluptatibus dolores doloremque porro sit vel voluptate doloribus. Minima ab totam impedit. Eaque voluptas tempora sint. Officiis tempora molestiae nemo veniam ipsa quaerat aliquid omnis sapiente. Sed odit iste mollitia labore est. Dolor temporibus aspernatur excepturi quasi odit aliquam. Ipsa ea corporis id voluptas repellat optio doloremque. Optio ut sit dolor. Excepturi nesciunt corrupti a sunt architecto quis beatae nobis et. Nisi optio vel tempora. Eum consequuntur culpa totam placeat quisquam nemo assumenda error iure. Asperiores provident omnis. Fugit quasi facilis ducimus voluptatem laborum placeat. Est exercitationem dignissimos iste facere doloremque. Pariatur ipsam magnam molestias odit animi esse autem nam molestiae. Neque saepe ad aliquid reprehenderit aliquid enim architecto suscipit. Consequatur minus ut ad aliquam architecto. Corrupti officia officiis iste enim. Id iure et culpa ad. Qui dignissimos a vel praesentium quia dolores. Voluptatem eius explicabo non omnis quaerat nam placeat earum. Expedita eligendi illum tenetur laborum iste necessitatibus sint ea fugit. Quasi quas dolores vel expedita assumenda eveniet error. Quis repellendus doloremque excepturi consequatur id exercitationem. Explicabo aliquam blanditiis. Quibusdam quaerat quisquam neque.
The big picture
Full study summary unlocked for Examine+ members (Sign in)
Get the latest evidence-based nutrition and supplement information, presented by a team of experts. Save time and money by learning what works.
Get started with Examine+ today.Possimus velit dolorem. Libero corrupti aspernatur vitae dolore excepturi quibusdam fuga. Quod sequi voluptatem asperiores assumenda maxime. Blanditiis error sed quisquam doloribus repudiandae error. Expedita doloremque in ex fuga. Quia eum eum magni illum. Vero officia ipsum a. Quia perferendis a tempore. Ea explicabo eligendi labore nihil debitis ab libero fugit laborum. Natus ullam quasi numquam. Magnam repellat in earum dicta doloremque. Nihil neque eius corporis animi voluptatum est iste eveniet. Neque eum nemo quasi veritatis eos impedit excepturi consequatur. Omnis soluta facere veniam reprehenderit. Fugiat aut officia exercitationem illo doloremque voluptate. Optio ut molestiae cupiditate distinctio nostrum. Totam magni provident fugiat expedita molestiae quas voluptate voluptatibus. Architecto hic beatae mollitia rem culpa consectetur. Accusamus omnis tempora beatae itaque rem neque rem incidunt. Recusandae deleniti ex similique facere ad eveniet iusto placeat. Nemo mollitia eaque eveniet. Unde voluptatem facere saepe unde sapiente necessitatibus commodi magnam possimus. Vitae dolor debitis laboriosam enim autem sequi quisquam tempora optio. Occaecati vero iusto rerum ratione voluptates doloremque qui ratione. Tempora porro doloribus esse eum eos. In debitis quas laboriosam labore laudantium similique totam aperiam. Quas sint perspiciatis aut harum. Unde quasi culpa numquam vitae nihil impedit sequi possimus. Ipsa unde quam debitis non provident. Unde sequi quibusdam rem velit adipisci.
Full study summary unlocked for Examine+ members (Sign in)
Blanditiis ad animi velit illum optio. Veritatis dignissimos omnis numquam fugit error itaque. Quo dolorem vitae nulla id maxime magnam. Veritatis repellendus ratione fugiat minima eveniet exercitationem voluptatem quibusdam. Ut est magni molestias nesciunt nostrum itaque ipsum. Possimus sunt possimus eos porro vel porro voluptatem esse.
Background
Nicotinamide, a form of vitamin B3, protects the body against oxidative stress, improves cell survival, and plays a role in DNA repair and regulation. It may even play a role in preventing and treating cancer.
The study
Full study summary unlocked for Examine+ members (Sign in)
Get the latest evidence-based nutrition and supplement information, presented by a team of experts. Save time and money by learning what works.
Get started with Examine+ today.Magnam modi occaecati officia laborum laborum. Repudiandae error inventore ipsam provident cumque dignissimos omnis excepturi. Accusantium deserunt soluta aliquam consequuntur eaque voluptatibus facere veritatis eveniet. Enim quas molestias fuga quod iste vel. Nisi fugit dignissimos similique illo. Beatae iure perspiciatis voluptatibus impedit facilis sint sunt. Aspernatur a aliquam quisquam maiores molestias porro. Nisi vero cum adipisci velit eius deleniti. Eos ab delectus distinctio a aspernatur. Dolores laboriosam rem aspernatur non tempore cumque asperiores aspernatur. Assumenda explicabo voluptates vel id corrupti quos accusantium. Fuga aut in iusto sunt qui nam fugiat. Alias inventore iusto quas in unde incidunt est. Aperiam ea alias praesentium ipsum minima sit harum inventore velit. Magni dicta unde dolorum. Omnis cupiditate adipisci pariatur totam ipsam dolores ullam non. Nisi soluta est sed reiciendis. A pariatur eum mollitia suscipit nesciunt. Fugiat recusandae nemo aspernatur dolores tempora minus fugiat. Quidem quae eligendi culpa assumenda iusto fuga assumenda quae. Dolore quaerat voluptatibus distinctio beatae praesentium saepe accusantium accusamus. Maxime incidunt distinctio iusto iure. Neque quidem animi nostrum dolorem fugit accusamus dolores. Dignissimos architecto ipsa incidunt laboriosam provident. Illum numquam libero. Ipsa incidunt ducimus esse ea temporibus est rerum dignissimos. Quis voluptates at minus maxime commodi.
The results
Full study summary unlocked for Examine+ members (Sign in)
Get the latest evidence-based nutrition and supplement information, presented by a team of experts. Save time and money by learning what works.
Get started with Examine+ today.Amet quidem corrupti maxime facilis accusamus. Numquam molestias eligendi temporibus neque neque dolor quisquam unde accusamus. Error temporibus non laboriosam facere consectetur non cumque. Sint molestias quam illum sed explicabo ea. Id quas earum error iusto voluptatum quisquam omnis quos. At maiores assumenda error. Iusto soluta cumque explicabo ad eligendi. Quam voluptatum adipisci mollitia culpa amet soluta. Officia similique voluptas autem cupiditate fugit impedit. Vitae incidunt consectetur atque ut dolor doloremque. Aut aliquam maxime ipsum sint. Atque cumque atque tenetur reprehenderit earum minus recusandae. Animi ipsa praesentium facilis aut non. Ea deserunt sed enim iure exercitationem iusto consequuntur. Maxime vel doloremque alias quidem consequatur minima fugit. Quo eveniet nemo eos. Eos qui unde distinctio reiciendis. Quia eum necessitatibus optio. Corporis hic corporis dolorem tempora laboriosam reiciendis magni molestias corporis. Corrupti fugiat culpa hic fugit tenetur. Ipsa sapiente vel.
Note
Full study summary unlocked for Examine+ members (Sign in)
Get the latest evidence-based nutrition and supplement information, presented by a team of experts. Save time and money by learning what works.
Get started with Examine+ today.Omnis hic repellat explicabo esse esse hic beatae. Fugit non earum. Sequi cum numquam. Assumenda dolore placeat dolorem doloremque perferendis sunt. Deleniti aliquid quibusdam explicabo officia asperiores iusto. Id quas reiciendis dolores consectetur vero. Possimus dolore numquam quidem ut. Laboriosam maxime distinctio fugit unde ab sunt error nesciunt saepe. Aspernatur tempore illo expedita porro vitae sed non eos. Tempore aliquid sapiente esse quis rem nobis. Earum deleniti animi. Ipsum quis animi sequi. Ullam maiores officiis. Nostrum ex ex. Praesentium at quidem perspiciatis earum iste. Odio iure voluptate beatae consectetur delectus sed molestias. Iusto aut unde consequatur. Voluptate atque a unde.
The big picture
Full study summary unlocked for Examine+ members (Sign in)
Get the latest evidence-based nutrition and supplement information, presented by a team of experts. Save time and money by learning what works.
Get started with Examine+ today.Excepturi voluptate quos ut. Molestiae quas temporibus molestias. Delectus fugiat excepturi commodi distinctio. Iure facilis voluptatem nesciunt provident earum mollitia odio. Tenetur mollitia qui. Iusto et et repellendus deserunt dolorem magnam aut consequatur. Sequi nemo doloribus placeat tempora deserunt. Ducimus blanditiis praesentium voluptatum voluptatum porro sapiente fuga. Voluptatum nam placeat dolorum unde vitae temporibus eum assumenda. Est error debitis autem aliquid dolorem iusto iusto ducimus iure. Nemo vero sed culpa illum exercitationem sit eligendi. Dolor delectus dolore reprehenderit vero modi numquam sunt totam. Et delectus vitae sapiente consequuntur vel sit. Eligendi voluptas nihil eum distinctio error perspiciatis mollitia nam nemo. Praesentium itaque quia accusantium numquam maxime dolores quo nihil. Officiis repellat perferendis. Illo recusandae ea voluptas quae eaque. Possimus consectetur commodi aut quia facilis. Harum aspernatur officia voluptas ad unde. Voluptatibus provident occaecati quia magni rerum. Sunt dicta quisquam ipsam dolorem accusamus pariatur repellat. Consequuntur atque voluptates sequi illum minima eos odio recusandae. Amet quaerat officia a earum aliquid similique ab sint. Quia animi ad. Rerum voluptatibus impedit fuga possimus doloribus praesentium blanditiis. Fuga cupiditate excepturi neque. Eius rem laborum architecto aspernatur illum blanditiis.
Recent evidence has linked B vitamins (specifically Vitamin B6 and vitamin-b12) to an increased risk of lung cancer in men, especially in smokers. Here, we analyze the study and interview the lead author, Dr. Theodore Brasky.
B vitamins are common ingredients of multivitamins, of course, but also of energy boosters, such as energy drinks. But while they are best known for their role in energy metabolism,[1] they may play a role in cancer biology through partaking in one-carbon metabolism[2] and thus in methylation reactions and DNA synthesis.
This hypothesis was substantiated in 2015 when a paper published by the New England Journal of Medicine caused a stir by reporting that nicotinamide (a form of vitamin B3 also known as niacinamide) could reduce the rate of new non-melanoma skin cancers.[3]
B vitamins had gained an “anti-cancer” reputation.
Yet it was just one study showing that one form of vitamin B3 could reduce the rate of one type of skin cancer; it didn’t preclude the possibility that some B vitamins could worsen at least some types of cancers.
To look for other possible connections between B vitamin supplementation and cancer, Dr. Theodore Brasky at The Ohio State University, in collaboration with colleagues at the Fred Hutchinson Cancer Research Center and at University of Taipei, performed a large observational study.[4] Since its publication in the Journal of Clinical Oncology, in 2017, this study has taken the supplement world by storm, for it linked the vitamins B6 and B12 each with a 30–40% increase in overall risk of lung cancer in men.
Let’s take a closer look at the study.
Study design
To look for possible connections between B vitamin supplementation and lung cancer, the researchers analyzed data from the 77,000 participants in the VITamins And Lifestyle (VITAL) prospective cohort study.[5] The study itself was designed to look for possible associations between cancer risk and vitamin, mineral, and non-vitamin/non-mineral supplementation.
The researchers chose to focus on the vitamins B6, B12, and B9, which play an important role in the one-carbon pathways and thus are most likely to affect carcinogenesis. The study participants, all residents of the State of Washington aged 50–76 at the beginning of the study, were classified into five groups based on their average daily dose of supplemental B vitamins over the previous 10 years. Statistical techniques were then used to adjust for confounding factors such as age, education, body size, and family history of lung cancer.
What were the results?
When the data were stratified by sex, B6 and B12 as individual supplements were each shown to increase lung cancer risk by 30–40% in men (but not in women).
The greatest risk was found among men with the highest average daily dose of B6 (>20 mg/day was associated with an 82% greater risk) and B12 (>55 mcg/day was associated with a 98% greater risk) over the ten years preceding the study.
When the data were stratified by smoking status, increased risk was associated with smoking. Smokers who had supplemented with high amounts of B6 had nearly three times the risk of developing lung cancer, and those having supplemented with high amounts of B12 had over three times the risk. The study found no association between supplementation and increased risk in either former smokers or recent smokers. As for never-smokers, the paper states they “were excluded from the smoking-stratified analysis because of the low number of participants with incident lung cancer in that group.”
The study showed that long-term supplementation with B6 or B12 increased lung-cancer risk in male current smokers, especially in those supplementing with high dosages of either vitamin.
What is the mechanism?
One-carbon chemical groups lack stability, so they need to be attached to larger molecules in a process called one-carbon metabolism. The vitamins B6, B9,[6] and B12 play an important part in one-carbon metabolism, which in turn plays a crucial part in methylation reactions and nucleotide synthesis.
The nucleus of each of your cells contains your complete DNA. In your DNA is encoded the genetic blueprint for every protein in your body. How then do cells maintain a unique identity? By each reading only certain parts of your DNA, so that only the appropriate genes are turned on at the appropriate time.
For that purpose, sections of your DNA can be “marked” with methyl groups that prevent the expression of nearby genes. This type of epigenetic imprinting is critical to keeping cells normal, healthy, and well behaved. When the process becomes dysfunctional, the wrong genes can be turned on at the wrong times, potentially leading to uncontrolled cell growth — to cancer.
So how would high amounts of B6 or B12 increase cancer risk? We might find some clues in a recent study on DNA methylation,[7] which found that two years of supplementation with 400 mcg of B9 and 500 mcg of B12 changed DNA methylation. Thus, the increase in cancer risk seen in the Brasky study could be caused, in part, by changes in DNA methylation from long-term B vitamin supplementation.
Another curious finding from the Brasky study was that only men saw an increase in cancer risk from B6 or B12 supplementation. Women did not. We know androgens regulate some of the enzymes that participate in one-carbon metabolism,[8] which might explain the difference.
Androgens and the vitamins B6, B9, and B12 interact to play a role in DNA methylation. Since DNA methylation in part determines which genes are activated (or not) at any given time, this could explain the link between long-term B vitamin supplementation and cancer risk in men.
What does this study mean?
The Brasky study was not designed to show causation, but it did reveal a strong correlation between increased risk of lung cancer and long-term B6/B12 supplementation, especially in high doses and among smokers. There are several ways B vitamins may interact with cancer metabolism; more research is needed to determine the exact mechanisms at work. In the meantime, we are left with three takeaways:
Smoking, as you know, causes lung cancer. If you smoke, stop. If you are unable to stop, avoid supplementing with B vitamins for an extended period of time, especially if you are male. Long-term B vitamin supplementation seems to increase cancer risk in male smokers, possibly by potentiating carcinogenesis in precancerous cells in response to the carcinogens in cigarette smoke (which would explain why only current smokers, not former or recent smokers, seem affected).
The effect of B vitamins on non-smokers is still uncertain. In this study, sample sizes for never-smokers were too small to evaluate associations accurately.
Although observational studies cannot show causation, the associations between B vitamins and cancer risk found in this study raise an important point, which is that high-dose, long-term consumption of any supplement can potentially interact with your biochemistry in unexpected ways. Exceeding the recommended, tested doses of even the most healthful micronutrients may not be innocuous.
Q&A with Dr. Theodore Brasky, PhD, lead author of the study
When this study was published, its finding that B vitamin supplements increased cancer risk in men generated a lot of press. But isn’t there some nuance to that finding, especially with regard to smoking habits? What ultimate take-home message can be extracted from the data?
The nuance is sort of centered around the general idea that once you start chopping up data, you lose precision. In epidemiology, our best estimates come from data reflecting the largest sample sizes. Our most cited finding was that long-term, high-dose supplementation of vitamin B6 and long-term, high-dose supplementation of vitamin B12 were each associated with about a doubling of lung-cancer risk in men. This is an entirely true representation of our results. However, when we drilled down further — and thus lost some precision — we found that this twofold increase in risk was an average across different groups of men, some with no increase in risk (men who had never smoked or had stopped smoking at the time the study began), and some with a threefold to fourfold increase in risk (men who smoked at the time the study began).
Here the scientist is left with two possibilities. Is the real finding (a) based on the larger sample size with more precise data? — men who use these supplements have twice the risk of lung cancer as do men who don’t use these supplements; or (b) based on the subgroups within men with less precise results? — men who currently smoke and who use these supplements have three to four times the risk of lung cancer as do men who currently smoke and don’t use these supplements. To me, the take-home message is the latter.
Supplementation dose, frequency, and duration are all important from a biological standpoint. How were those factors taken into account in the design of the study questionnaire? What were the pros and cons of the different ways of using those factors (and others) to identify meaningful associations with lung-cancer risk?
Put simply, we had a number of options. We could analyze separately a given supplement’s frequency of use (i.e., days per week), duration of use (i.e., number of years in the past 10 [our questionnaire only asked about the past 10 years of use]), and most common dose used, or we could combine those data.
Analyzing separately any single aspect removes the influence of the other two, which is, in my view, not ideal. Combining the data gives two additional options. We could determine a cumulative dose over the past 10 years or an average daily dose over the past 10 years. We chose the latter because it’s easier to understand and because it allowed us to compare risks with what might be expected for intakes at the level of a multivitamin taken daily for the same amount of time.
However, the disadvantage of this option — which, I contend, remains better than the alternatives — is that the 10-year, daily-dose calculation equates short-term, high-dose intakes with long-term, lower-dose intakes. The highest category of intake for supplemental B12, for instance, was >55 mcg/day. This is >55 mcg taken daily, on average, over 10 years. For some people, it may actually have been about that amount daily for 10 years, but for most it was shorter-term use at higher doses that averaged out to this level.
Therefore, >55 mcg is not meant to be interpreted as the actual dose that might confer risk. Indeed, most B12 supplements are sold at much, much higher doses. A standard pill from a bottle at the grocery store might contain between 500 and 2,000 mcg, with instructions that it should be taken daily. This is why the comparison to what might be consumed from a multivitamin (100% RDA) comes in handy.
Although the question “Does B vitamin supplementation increase cancer risk?” is straightforward, extracting a solid answer from a given study population is another matter. Epidemiologists like yourself are experts at identifying risk associations within large study populations. At the other end of the spectrum, basic scientists like myself tend to use defined experimental models to identify important cellular/molecular controls that drive disease processes. Could you comment on how epidemiological studies and basic science (i.e., bench research) fit in the big picture of biomedical science? Do you feel they complement each other?
A better scientist than I could probably comment on this with real nuance. I can only give my interpretation, which is, sadly, not based off any firsthand experience with bench science. I once pipetted something, but my assay didn’t run properly. C’est la vie. Looking broadly across disciplines, I can say that epidemiologists and “basic” scientists have a complementary relationship born out of necessity.
Epidemiologists cite rodent studies because in these experiments a lot of the variables can be controlled. The animals are very similar genetically, they’re all fed the same diet (unless it’s a nutrition study), handled the same way, etc. Moreover, we can perform some trials in animals that are considered unethical in humans — exposing rodents to tobacco smoke, for instance. We often see the results of these studies as hypothesis generating because, after all, the animal is a model for the human. People do not, in fact, have fur or tails, and we are much more genetically diverse than rodents purpose bred for disease models. In some instances, animal models are better approximations than others. Mice have estrous cycles rather than menstrual cycles, so some similarities for reproductive cancers are muddied by physiology here. Similarly, a mouse’s prostate gland is structured differently from a man’s; again, models. The idea is the same for work involving cells in petri dishes, although the contrast is starker. On the other hand, from what I’m told by my colleagues in these fields, epidemiologic research, which is predominantly done in an observational manner, is seen as hypothesis generating.
That we all work together towards the same goal is what’s important. Although we definitely give each other grief, epidemiologists appreciate basic scientists for their explanation of biologic mechanisms, and (I’m assuming) basic scientists appreciate epidemiologists for their findings in need of biologic explanation.
🚧 Under Renovation 🚧
The information in this section is slated for renovation — it will soon be transformed into a more usable (and readable!) form in the coming months. As such, the text in this section may be out of date and not up to Examine’s current standards for writing style.
- ^Depeint F, Bruce WR, Shangari N, Mehta R, O'Brien PJMitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolismChem Biol Interact.(2006 Oct 27)
- ^Selhub JFolate, vitamin B12 and vitamin B6 and one carbon metabolismJ Nutr Health Aging.(2002)
- ^Chen AC, Martin AJ, Choy B, Fernández-Peñas P, Dalziell RA, McKenzie CA, Scolyer RA, Dhillon HM, Vardy JL, Kricker A, St George G, Chinniah N, Halliday GM, Damian DLA Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer ChemopreventionN Engl J Med.(2015 Oct 22)
- ^Brasky TM, White E, Chen CLLong-Term, Supplemental, One-Carbon Metabolism-Related Vitamin B Use in Relation to Lung Cancer Risk in the Vitamins and Lifestyle (VITAL) CohortJ Clin Oncol.(2017 Oct 20)
- ^White E, Patterson RE, Kristal AR, Thornquist M, King I, Shattuck AL, Evans I, Satia-Abouta J, Littman AJ, Potter JDVITamins And Lifestyle cohort study: study design and characteristics of supplement usersAm J Epidemiol.(2004 Jan 1)
- ^Kim YIFolate and colorectal cancer: an evidence-based critical reviewMol Nutr Food Res.(2007 Mar)
- ^Kok DE, Dhonukshe-Rutten RA, Lute C, Heil SG, Uitterlinden AG, van der Velde N, van Meurs JB, van Schoor NM, Hooiveld GJ, de Groot LC, Kampman E, Steegenga WTThe effects of long-term daily folic acid and vitamin B12 supplementation on genome-wide DNA methylation in elderly subjectsClin Epigenetics.(2015 Nov 14)
- ^Corbin JM, Ruiz-Echevarría MJOne-Carbon Metabolism in Prostate Cancer: The Role of Androgen SignalingInt J Mol Sci.(2016 Jul 27)
- Low-density lipoprotein (LDL) - Westphal S, Borucki K, Taneva E, Makarova R, Luley CExtended-release niacin raises adiponectin and leptinAtherosclerosis.(2007 Aug)
- Low-density lipoprotein (LDL) - Kelly JJ, Lawson JA, Campbell LV, Storlien LH, Jenkins AB, Whitworth JA, O'Sullivan AJEffects of nicotinic acid on insulin sensitivity and blood pressure in healthy subjectsJ Hum Hypertens.(2000 Sep)
- Ketone Bodies - Chen X, Iqbal N, Boden GThe effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjectsJ Clin Invest.(1999 Feb)
- Insulin - Chang AM, Smith MJ, Galecki AT, Bloem CJ, Halter JBImpaired beta-cell function in human aging: response to nicotinic acid-induced insulin resistanceJ Clin Endocrinol Metab.(2006 Sep)
- Insulin - Fraterrigo G, Fabbrini E, Mittendorfer B, O'Rahilly S, Scherer PE, Patterson BW, Klein SRelationship between Changes in Plasma Adiponectin Concentration and Insulin Sensitivity after Niacin TherapyCardiorenal Med.(2012 Aug)
- Wound Healing - Gebicki J, Sysa-Jedrzejowska A, Adamus J, Woźniacka A, Rybak M, Zielonka J1-Methylnicotinamide: a potent anti-inflammatory agent of vitamin originPol J Pharmacol.(2003 Jan-Feb)
- Blood glucose - Valeria Nasser Figueiredo, Felipe Vendrame, Bruno A Colontoni, Thiago Quinaglia, Jose Roberto Matos-Souza, Filipe Azevedo Moura, Otavio R Coelho, Eliana C de Faria, Andrei C SpositoShort-term effects of extended-release niacin with and without the addition of laropiprant on endothelial function in individuals with low HDL-C: a randomized, controlled crossover trialClin Ther.(2014 Jun 1)
- Apolipoprotein B - T Sakai, V S Kamanna, M L KashyapNiacin, but not gemfibrozil, selectively increases LP-AI, a cardioprotective subfraction of HDL, in patients with low HDL cholesterolArterioscler Thromb Vasc Biol.(2001 Nov)
- Total cholesterol - No authors listedClofibrate and niacin in coronary heart diseaseJAMA.(1975 Jan 27)
- Stroke Risk - Jasleen K. Duggal, Mukesh Singh, Navneet Attri, Param P. Singh, Neyaz Ahmed, Suneet Pahwa, Janos Molnar, Sarabjeet Singh, Sandeep Khosla, Rohit AroraEffect of Niacin Therapy on Cardiovascular Outcomes in Patients With Coronary Artery DiseaseJournal of Cardiovascular Pharmacology and Therapeutics.()
- High-density lipoprotein (HDL) - Blond E, Rieusset J, Alligier M, Lambert-Porcheron S, Bendridi N, Gabert L, Chetiveaux M, Debard C, Chauvin MA, Normand S, Roth H, de Gouville AC, Krempf M, Vidal H, Goudable J, Laville M, “Niacin” Study GroupNicotinic acid effects on insulin sensitivity and hepatic lipid metabolism: an in vivo to in vitro studyHorm Metab Res.(2014 Jun)
- Apolipoprotein A - AIM-HIGH Investigators, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, McBride R, Teo K, Weintraub WNiacin in patients with low HDL cholesterol levels receiving intensive statin therapyN Engl J Med.(2011 Dec 15)
- Apolipoprotein B - Fabbrini E, Mohammed BS, Korenblat KM, Magkos F, McCrea J, Patterson BW, Klein SEffect of fenofibrate and niacin on intrahepatic triglyceride content, very low-density lipoprotein kinetics, and insulin action in obese subjects with nonalcoholic fatty liver diseaseJ Clin Endocrinol Metab.(2010 Jun)
- Erythema - Bissett DL, Oblong JE, Berge CANiacinamide: A B vitamin that improves aging facial skin appearanceDermatol Surg.(2005 Jul)
- Skin Quality - Hakozaki T, Minwalla L, Zhuang J, Chhoa M, Matsubara A, Miyamoto K, Greatens A, Hillebrand GG, Bissett DL, Boissy REThe effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transferBr J Dermatol.(2002 Jul)
- Acne Symptoms - Khodaeiani E, Fouladi RF, Amirnia M, Saeidi M, Karimi ERTopical 4% nicotinamide vs. 1% clindamycin in moderate inflammatory acne vulgarisInt J Dermatol.(2013 Aug)
- Acne Symptoms - Shalita AR, Smith JG, Parish LC, Sofman MS, Chalker DKTopical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgarisInt J Dermatol.(1995 Jun)