Витамины как кофакторы

Кратко

Большинство витаминов превращается в организме в небольшие вспомогательные молекулы, необходимые для работы конкретных ферментов. Поэтому при недостатке одного витамина замедляется определённая группа реакций и развивается характерное нарушение, например бери-бери, пеллагра, цинга или повышенная кровоточивость. В крупных испытаниях с участием взрослых без выявленного дефицита витаминные добавки почти или совсем не защищали от болезней сердца, рака и смерти.

Коферменты из витаминов группы B

Большинство витаминов группы B превращается в коферменты — небольшие молекулы, необходимые для работы определённых ферментов ¹²³⁴.

Витамин	Кофермент	Ферменты или реакции	Дефицит
Тиамин (B1)	Тиаминпирофосфат	Пируватдегидрогеназа, 2-оксоглутаратдегидрогеназа и дегидрогеназа 2-оксокислот с разветвлённой цепью; транскетолаза ¹	Бери-бери, энцефалопатия Вернике ¹
Рибофлавин (B2)	ФМН, ФАД	Глутатионредуктаза, MTHFR ²	Арибофлавиноз: хейлоз, глоссит, анемия ²
Ниацин (B3)	НАД+, НАДФ+	Дегидрогеназы ³	Пеллагра ³
Пантотеновая кислота (B5)	Кофермент А	Перенос ацильных групп ⁵	Встречается редко ⁵
Витамин B6	Пиридоксаль-5′-фосфат	Аминотрансферазы, декарбоксилазы, гликогенфосфорилаза ⁴	Микроцитарная анемия, судороги ⁴
Биотин (B7)	Связанный с ферментом биотин	Ацетил-КоА-карбоксилаза, пируваткарбоксилаза, пропионил-КоА-карбоксилаза и β-метилкротонил-КоА-карбоксилаза ⁶	Дерматит, выпадение волос, атаксия ⁶
Фолаты (B9)	Тетрагидрофолат	Перенос одноуглеродных фрагментов при синтезе оснований ДНК и метионина ⁷	Мегалобластная анемия ⁸
Витамин B12	Метилкобаламин, аденозилкобаламин	Метионинсинтаза, метилмалонил-КоА-мутаза ⁹	Мегалобластная анемия, миелонейропатия ⁸

В пируватдегидрогеназном комплексе компонент E1 с участием тиаминпирофосфата декарбоксилирует пируват и восстановительно ацетилирует липоильную группу компонента E2; затем E2 переносит ацетильную группу на кофермент А, а E3 с участием ФАД и НАД+ вновь окисляет дигидролипоильную группу ¹⁰.

Цикл липоильной группы пируватдегидрогеназного комплексаМитохондриальный матрикс

S-Ацетилдигидролипоил-E2Дигидролипоил-E2Дигидролипоамидацетилтрансфераза (E2; DLAT)Кофермент А → ацетил-КоА
Дигидролипоил-E2Липоил-E2Дигидролипоамиддегидрогеназа (E3; DLD)ФАД, НАД+ → НАДНЭлектроны переносятся с дигидролипоильной группы на ФАД, а затем на НАД+
Липоил-E2S-Ацетилдигидролипоил-E2Пируватдегидрогеназа (E1; PDHA1, PDHB)Тиаминпирофосфат, Mg2+, Пируват → CO2Декарбоксилирует пируват, затем восстановительно ацетилирует липоильную группу

При дефиците B12 фолаты задерживаются в форме 5-метилтетрагидрофолата, как описано в главе об обмене одноуглеродных фрагментов ⁸.

Витамин C и коллаген

Витамин C должен поступать в организм человека с пищей; он необходим для синтеза коллагена — основного белка кожи, костей и соединительной ткани ¹¹.

Аскорбат поддерживает ион металла в составе диоксигеназ в восстановленном состоянии, а пролил- и лизилгидроксилазам проколлагена он необходим для проявления максимальной активности ¹¹. Пролил-4-гидроксилаза — фермент, содержащий негемовое железо, — образует 4-гидроксипролин, который значительно повышает термостабильность тройной спирали коллагена ¹². У взрослых цинга, проявляющаяся кровоточивостью дёсен, кровоподтёками и плохим заживлением ран, развивается при концентрации аскорбата в плазме ниже 10 µmol/L; для её предотвращения достаточно 10 mg витамина C в сутки ¹¹.

Витамин K и варфарин

Витамин K необходим для активации ряда белков свёртывания крови, а варфарин действует, блокируя его регенерацию ¹³.

γ-Глутамилкарбоксилаза превращает остатки глутамата факторов II, VII, IX и X и протеинов C, S и Z в остатки γ-карбоксиглутамата, одновременно окисляя гидрохинон витамина K до эпоксида ¹³. Эпоксидредуктаза витамина K восстанавливает эпоксид до хинона, а затем до гидрохинона; варфарин ингибирует обе реакции ¹⁴.

Цикл витамина KМембрана эндоплазматического ретикулума, особенно в печени и костной ткани

Гидрохинон витамина KЭпоксид витамина Kγ-Глутамилкарбоксилаза (GGCX)Глутамат → γ-карбоксиглутамат, CO2, O2Карбоксилирует факторы II, VII, IX и X и протеины C, S и Z
Эпоксид витамина KХинон витамина KЭпоксидредуктаза витамина K (VKORC1)ВарфаринПри каждом восстановлении окисляются два цистеина активного центра фермента
Хинон витамина KГидрохинон витамина KЭпоксидредуктаза витамина K (VKORC1)Варфарин

Эту редуктазу кодирует ген VKORC1; вариант c.-1639G>A в его промоторе снижает экспрессию фермента и необходимую дозу варфарина ¹⁵. Дефицит витамина K удлиняет протромбиновое время и вызывает кровотечения ¹³. В странах Западной Европы при отсутствии профилактики частота поздних кровотечений, обусловленных дефицитом витамина K, составляла 4,4–7,2 случая на 100 000 новорождённых; относительный риск оценивался в 81 ¹³.

Витаминные добавки у взрослых без дефицита

В испытаниях с участием взрослых без выявленного дефицита витаминные добавки почти или совсем не защищали от сердечно-сосудистых заболеваний, рака и смерти ¹⁶.

Согласно обзору данных, подготовленному для Рабочей группы по профилактическим услугам США (USPSTF), в двух испытаниях с участием 15 031 человека приём витамина C по 500 mg в сутки в течение 3–8 лет пользы не принёс ¹⁶. Приём поливитаминов был связан с более низкой заболеваемостью раком (отношение шансов 0,93; 95% ДИ 0,87–0,99; 4 испытания, 48 859 участников); в испытаниях с достаточной статистической мощностью абсолютная разница составила от −0,2 до −1,2 процентного пункта ¹⁶.

Результаты исследований, финансированных индустрией

Исследование Physicians’ Health Study II финансировали Национальные институты здравоохранения США (NIH) и компания BASF, которая предоставила витамин C и не участвовала в анализе данных ¹⁷. Среди 14 641 врача-мужчины при среднем сроке наблюдения 8,0 года серьёзные сердечно-сосудистые события произошли у 619 из 7329 участников (8,45%), получавших витамин C по 500 mg в сутки, и у 626 из 7312 (8,56%), получавших плацебо (отношение рисков 0,99; 95% ДИ 0,89–1,11); разница составила −0,1 процентного пункта ¹⁷.

Источники

Регуляторное
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), Turck D, Bresson JL, Burlingame B, Dean T, Fairweather-Tait S, et al. Dietary reference values for thiamin EFSA Journal, 2016.
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Финансирование и результат
Финансирование
European Food Safety Authority, on request from the European Commission (question EFSA-Q-2011-01225).
Результат
Free thiamin is the precursor of thiamin diphosphate (TDP, thiamin pyrophosphate), the coenzyme of pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and branched-chain alpha-keto acid dehydrogenase and of transketolase in the pentose phosphate pathway; the three dehydrogenases also require cofactors derived from pantothenic acid, riboflavin and niacin. Thiamin deficiency causes several forms of beriberi, dry (sensory and motor peripheral neuropathy) and wet (with congestive heart failure), and Wernicke's encephalopathy and Korsakoff's syndrome.
Регуляторное
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), Turck D, Bresson JL, Burlingame B, Dean T, Fairweather-Tait S, et al. Dietary Reference Values for riboflavin EFSA Journal, 2017.
doi:10.2903/j.efsa.2017.4919 PubMed 32625611
Финансирование и результат
Финансирование
European Food Safety Authority, on request from the European Commission (question EFSA-Q-2011-01222).
Результат
Riboflavin is the integral part of the coenzymes FAD and FMN, cofactors of flavoprotein enzymes; flavokinase phosphorylates free riboflavin to FMN, which FAD synthetase converts to FAD. Glutathione reductase uses FAD, methylenetetrahydrofolate reductase (MTHFR) requires FAD, and pyridoxamine phosphate oxidase is FMN-dependent. Signs of riboflavin deficiency (ariboflavinosis) are unspecific: sore throat, hyperaemia and oedema of the pharyngeal and oral mucous membranes, cheilosis, glossitis, seborrhoeic dermatitis, angular stomatitis and normochromic normocytic anaemia.
Регуляторное
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on Dietary Reference Values for niacin EFSA Journal, 2014.
doi:10.2903/j.efsa.2014.3759
Финансирование и результат
Финансирование
European Food Safety Authority, on request from the European Commission (question EFSA-Q-2011-01218).
Результат
Niacin (nicotinic acid and nicotinamide) is the precursor of the coenzymes NAD and NADP; many dehydrogenases use NAD or NADP or both, and NAD also takes part in non-redox ADP-ribose transfer reactions. About 60 mg of tryptophan yields 1 mg of niacin. Long-term inadequate intake of tryptophan and niacin can lead to pellagra, with photosensitive dermatitis, tongue and mouth soreness, vomiting, diarrhoea, depression and dementia; untreated pellagra results in death from multiorgan failure.
Регуляторное
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Dietary Reference Values for vitamin B6 EFSA Journal, 2016.
doi:10.2903/j.efsa.2016.4485 PubMed 40007837
Финансирование и результат
Финансирование
European Food Safety Authority, on request from the European Commission (question EFSA-Q-2011-01228).
Результат
All six vitamin B6 derivatives can be converted in the body to pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate, cofactors of more than 100 enzymes. PLP serves enzymes of amino acid decarboxylation, transamination and racemisation and is a cofactor of glycogen phosphorylase, delta-aminolevulinate synthase, serine hydroxymethyltransferase, cystathionine beta-synthase and cystathionine gamma-lyase. Vitamin B6 deficiency is rare; its most typical features are hypochromic microcytic anaemia and neurological abnormalities, including convulsive seizures.
Регуляторное
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on Dietary Reference Values for pantothenic acid EFSA Journal, 2014.
doi:10.2903/j.efsa.2014.3581
Финансирование и результат
Финансирование
European Food Safety Authority, on request from the European Commission (question EFSA-Q-2011-01219).
Результат
Pantothenic acid is a component of coenzyme A and acyl-carrier proteins and serves in acyl-group activation and transfer. It is ubiquitous in foods and dietary deficiency is rare; deficiency symptoms, including mood changes and sleep, neurological, cardiac and gastrointestinal disturbances, have been described in subjects on a pantothenic acid antagonist and/or a pantothenic acid-deficient diet.
Регуляторное
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on Dietary Reference Values for biotin EFSA Journal, 2014.
doi:10.2903/j.efsa.2014.3580
Финансирование и результат
Финансирование
European Food Safety Authority, on request from the European Commission (question EFSA-Q-2011-01205).
Результат
Biotin is a cofactor of acetyl-CoA carboxylase, propionyl-CoA carboxylase, beta-methylcrotonyl-CoA carboxylase and pyruvate carboxylase, to which it is covalently attached in the cell; biotinidase releases biotin from degraded holocarboxylases for reuse. Dietary biotin deficiency is rare and is characterised by fine scaly dermatitis, hair loss, conjunctivitis, ataxia and delayed child development; cases occurred with long-term parenteral nutrition without biotin, in biotinidase deficiency and after large intakes of raw eggs, whose egg-white avidin prevents biotin absorption.
Независимое
Ducker GS, Rabinowitz JD. One-Carbon Metabolism in Health and Disease Cell Metabolism, 2017.
doi:10.1016/j.cmet.2016.08.009 PubMed 27641100
Финансирование и результат
Финансирование
G.S.D. is supported by a postdoctoral fellowship from the American Cancer Society (PF-15-190-01-TBE). J.D.R. is supported by NIH grants R01CA163591 and P30DK019525 and Stand Up to Cancer.
Результат
Review. Animals require dietary folate. Tetrahydrofolate (THF) binds one-carbon units at N5 and N10 at three oxidation states: 5-methyl-THF, the most reduced, 5,10-methylene-THF and 10-formyl-THF, the most oxidised; folic acid is reduced to dihydrofolate (DHF) and then THF. SHMT1 (cytosol) and SHMT2 (mitochondria) interconvert serine and glycine with THF and 5,10-methylene-THF, reversibly; in rapidly proliferating cultured cells the main direct source of cytosolic one-carbon units is formate released from mitochondria, reassimilated by the trifunctional MTHFD1. TYMS methylates dUMP to dTMP with 5,10-methylene-THF and is the only folate enzyme that alters THF itself, taking two electrons from it and producing DHF; DHFR regenerates THF with NADPH and is the target of trimethoprim and methotrexate, which trap folate as DHF. Purine synthesis incorporates two 10-formyl-THF units; in proliferating cells each new DNA or RNA base needs on average one 10-formyl-THF, and 5,10-methylene-THF is needed for one in four DNA bases. 5-Fluorouracil is a suicide inhibitor of TYMS; methotrexate most potently blocks DHFR, whereas pemetrexed more potently inhibits TYMS and AICAR transformylase; 5-formyl-THF (folinic acid, leucovorin) is given as rescue. 5-Methyl-THF, made by cytosolic NADPH-dependent MTHFR, is consumed only by cobalamin-dependent methionine synthase; BHMT is limited to liver and kidney. SAM inhibits MTHFR and activates CBS; 5-methyl-THF inhibits GNMT. Transsulfuration is the only route that degrades homocysteine. Folate and cobalamin supplementation lower homocysteine without reducing cardiovascular events in the general population. Dietary folate deficiency in adults manifests as macrocytic anaemia.
Регуляторное
EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA Panel), Turck D, Bohn T, Castenmiller J, de Henauw S, Hirsch-Ernst KI, et al. Scientific opinion on the tolerable upper intake level for folate EFSA Journal, 2023.
doi:10.2903/j.efsa.2023.8353 PubMed 37965303
Финансирование и результат
Финансирование
European Food Safety Authority, on request from the European Commission (question EFSA-Q-2021-00366). Preparatory systematic reviews were conducted by a contractor, Karolinska Institutet in collaboration with the University of Oslo, under an EFSA procurement procedure.
Результат
Folates consist of a pterin moiety linked to p-aminobenzoic acid and one or more glutamates, substituted at N5 or N10 by one-carbon units; natural folates are reduced polyglutamates usually with five to seven glutamates. A jejunal hydrolase (EC 3.4.17.21) converts polyglutamates to monoglutamates, which PCFT (SLC46A1), the most important intestinal transporter, and RFC (SLC19A1) move into enterocytes; 5-methyl-THF is the main circulating form; RFC, the main transporter from blood to tissues, has about 100 times lower affinity for folic acid than for reduced folates. Folylpolyglutamate synthase retains folates as THF polyglutamates; 5-methyl-THF monoglutamate and folic acid are poor substrates, and 5-methyl-THF is lost from cells unless methionine synthase converts it to THF. Folic acid, a fully oxidised monoglutamate, is reduced by DHFR via dihydrofolate to THF. The MTHFR reaction is essentially irreversible under physiological conditions and SAM is its allosteric inhibitor; in cobalamin deficiency 5-methyl-THF is metabolically trapped, SAM falls, MTHFR becomes fully active, and a functional folate deficiency develops with raised plasma 5-methyl-THF and homocysteine, depleted erythrocyte folate and fewer methyl groups for transmethylation. The megaloblastic anaemia of cobalamin deficiency is identical to that of folate deficiency; neurological manifestations (myeloneuropathy from demyelination) can occur with or without anaemia, are almost never seen in folate deficiency, and have an unknown mechanism, with congenital defects of MTHFR and methionine synthase pointing to methionine synthase rather than methylmalonyl-CoA mutase. Folic acid can initiate DNA synthesis in cobalamin deficiency through DHFR but cannot correct the methylation defect. MTHFR 677TT is associated with lower serum folate and higher homocysteine; in a genome-wide study of 2232 Irish adults aged 18 to 28 years MTHFR 677C>T was the only significant modifier of red cell and serum folate. ULs for folic acid retained: 1000 ug/day for adults including pregnant and lactating women, with progression of neurological symptoms in cobalamin-deficient patients as critical effect.
Независимое
Gherasim C, Lofgren M, Banerjee R. Navigating the B12 Road: Assimilation, Delivery, and Disorders of Cobalamin Journal of Biological Chemistry, 2013.
doi:10.1074/jbc.R113.458810 PubMed 23539619
Финансирование и результат
Финансирование
This work was supported, in whole or in part, by National Institutes of Health Grant DK45776.
Результат
Review. Mammals have two B12-dependent enzymes: methionine synthase, which uses methylcobalamin, and methylmalonyl-CoA mutase, which uses adenosylcobalamin to convert methylmalonyl-CoA to succinyl-CoA. Methionine synthase works in two half-reactions: methylcobalamin methylates homocysteine to methionine, leaving cob(I)alamin, which removes the methyl group from 5-methyl-THF to give THF and methylcobalamin; occasional oxidation to cob(II)alamin is repaired by reductive methylation needing NADPH, methionine synthase reductase and S-adenosylmethionine. Food cobalamin binds haptocorrin; in the duodenum pancreatic proteases release it, intrinsic factor binds it, and intestinal cells take it up by cubilin/AMN receptor-mediated endocytosis. About 20% of circulating cobalamin is bound to transcobalamin, which delivers it to cells through the transcobalamin receptor. Mutations in the cblG (methionine synthase) and cblE (reductase) loci cause isolated hyperhomocysteinaemia without methylmalonic aciduria.
Независимое
Patel MS, Nemeria NS, Furey W, Jordan F. The Pyruvate Dehydrogenase Complexes: Structure-based Function and Regulation Journal of Biological Chemistry, 2014.
doi:10.1074/jbc.R114.563148 PubMed 24798336
Финансирование и результат
Финансирование
Supported, in whole or in part, by National Institutes of Health grants DK 20478 (to M.S.P.), GM050380 (to F.J.) and GM061791 (to W.F.) and by the Veterans Affairs Merit Review (W.F.).
Результат
Review. The pyruvate dehydrogenase complex links glycolysis to the tricarboxylic acid cycle and comprises pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and dihydrolipoamide dehydrogenase (E3), which work sequentially. E1, a thiamin diphosphate-dependent enzyme, decarboxylates pyruvate and reductively acetylates the lipoyl groups covalently attached to E2; E2 transfers the acetyl group to CoA, forming acetyl-CoA; E3 transfers electrons from the dihydrolipoyl groups of E2 to FAD and then to NAD+.
Регуляторное
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on Dietary Reference Values for vitamin C EFSA Journal, 2013.
doi:10.2903/j.efsa.2013.3418
Финансирование и результат
Финансирование
European Food Safety Authority, on request from the European Commission (question EFSA-Q-2011-01229).
Результат
Vitamin C is an essential component of the diet, as humans and other primates have lost the ability to synthesise it. It is a cofactor of monooxygenases, dioxygenases and mixed function oxygenases, reducing the active-centre metal ion and maintaining it in a reduced state. Procollagen-proline dioxygenase and procollagen-lysine 5-dioxygenase require vitamin C for maximal activity, and deficiency impairs the synthesis of collagen, the principal protein of skin, bones, teeth and connective tissues. Scurvy occurs in adults at a plasma ascorbate below 10 umol/L and a body pool below 300 mg, with tooth loss, joint pain, poor wound healing, petechiae, bruising and inflamed, bleeding gums; an intake of 10 mg/day prevents it.
Независимое
Shoulders MD, Raines RT. Collagen structure and stability Annual Review of Biochemistry, 2009.
doi:10.1146/annurev.biochem.77.032207.120833 PubMed 19344236
Финансирование и результат
Финансирование
Collagen research in the authors' laboratory is supported by NIH grant AR044276; M.D.S. was supported by graduate fellowships from the Department of Homeland Security and the Division of Medicinal Chemistry, American Chemical Society.
Результат
Review. Prolyl 4-hydroxylase, a non-haem iron enzyme, hydroxylates proline residues in the Yaa position of collagen Xaa-Yaa-Gly triplets to (2S,4R)-4-hydroxyproline. Hydroxylation of Yaa-position proline increases dramatically the thermal stability of collagen triple helices, and prolyl 4-hydroxylase activity is required for the viability of Caenorhabditis elegans and the mouse.
Регуляторное
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), Turck D, Bresson JL, Burlingame B, Dean T, Fairweather-Tait S, et al. Dietary reference values for vitamin K EFSA Journal, 2017.
doi:10.2903/j.efsa.2017.4780 PubMed 32625486
Финансирование и результат
Финансирование
European Food Safety Authority, on request from the European Commission (question EFSA-Q-2011-01232).
Результат
Vitamin K is the cofactor of gamma-glutamyl carboxylase (GGCX), which converts glutamic acid residues of vitamin K-dependent proteins, including coagulation factors II, VII, IX and X and the anticoagulant proteins C, S and Z, into calcium-binding gamma-carboxyglutamic acid residues; vitamin K hydroquinone is converted to vitamin K epoxide and reduced back by vitamin K epoxide reductase (VKOR), the step of the cycle blocked by warfarin. In adults, deficiency causes a bleeding tendency with a vitamin K-responsive increase in prothrombin time. In infants not given vitamin K prophylaxis, late vitamin K deficiency bleeding occurred in 4.4 to 7.2 per 100,000 births in Western European countries; its relative risk without prophylaxis is estimated at 81.
Независимое
Liu S, Li S, Shen G, Sukumar N, Krezel AM, Li W. Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation Science, 2021.
doi:10.1126/science.abc5667 PubMed 33154105
Финансирование и результат
Финансирование
W.L. is supported by NHLBI (R01 HL121718), the W. M. Keck Foundation (Forefront of Science Award), the Children's Discovery Institute (MCII 2020-854), NEI (R21 EY028705) and NIGMS (R01 GM131008). The NECAT beamlines are funded by NIGMS (P30 GM124165), the Eiger detector by NIH-ORIP (HEI S10OD021527), and the Advanced Photon Source by DOE (DE-AC02-06CH11357).
Результат
Eleven crystal structures of human vitamin K epoxide reductase (VKOR) and a VKOR-like paralog with substrates and antagonists. VKOR is an endoplasmic reticulum membrane enzyme; the cycle begins with epoxidation of vitamin K hydroquinone, which drives gamma-carboxylation of coagulation factors, and VKOR reduces the epoxide first to the quinone and then to the hydroquinone, each step coupled to oxidation of two active-site cysteines. Vitamin K antagonists, including warfarin, inhibit VKOR at both the epoxide and the quinone reduction steps.
Справочное издание
Dean L, Kane M. Warfarin Therapy and VKORC1 and CYP Genotype Medical Genetics Summaries, National Center for Biotechnology Information (US), 2026.
PubMed 28520347
Финансирование и результат
Финансирование
not stated in the chapter
Результат
Peer-reviewed chapter, first posted 8 March 2012, version 4.0 of 16 June 2026. VKORC1, on chromosome 16p11.2, encodes vitamin K epoxide reductase, which catalyses the rate-limiting step of vitamin K recycling and is the target of warfarin. The promoter variant c.-1639G>A (rs9923231) is associated with lower protein expression, increased warfarin sensitivity and lower dose requirements; the variant allele is the major allele (about 90%) in Asian populations and has a frequency of about 40% in people of European descent and 14% in African Americans. VKORC1 accounts for about 30% of the variation in dose requirement, CYP2C9 usually for less than 10%.
Независимое
O'Connor EA, Evans CV, Ivlev I, Rushkin MC, Thomas RG, Martin A, et al. Vitamin, Mineral, and Multivitamin Supplementation for the Primary Prevention of Cardiovascular Disease and Cancer: A Systematic Evidence Review for the U.S. Preventive Services Task Force Agency for Healthcare Research and Quality, Evidence Synthesis No. 209, 2022.
PubMed 35767665
Финансирование и результат
Участники
739 803
Финансирование
Prepared by the Kaiser Permanente Research Affiliates Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality (Contract No. HHSA-290-2015-00007-I, Task Order No. 75Q80118F32006). USPSTF liaisons were consulted on the analytic framework and key questions, and an AHRQ Medical Officer provided project oversight and reviewed the drafts; the USPSTF and AHRQ had no role in study selection, quality assessment or writing.
Результат
Vitamin and mineral supplementation provided little to no benefit in preventing cancer, cardiovascular disease and death, except a possible small benefit of multivitamins for any cancer (OR 0.93, 95% CI 0.87 to 0.99; 4 RCTs, n=48,859; absolute risk difference among adequately powered trials -0.2% to -1.2%); the multivitamin evidence rested on only three adequately powered trials, one with a median of 3.6 years of use and another limited to antioxidants. Two vitamin C trials (n=15,031) of 500 mg/day for 3 to 8 years suggested no benefit for mortality, cardiovascular disease or cancer. The report's suggested citation gives 2022; PubMed lists June 2021.
Финансировано индустрией
Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, et al. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial JAMA, 2008.
doi:10.1001/jama.2008.600 PubMed 18997197
Финансирование и результат
Регистрация
NCT00270647
Участники
14 641
Наблюдение
mean 8.0 years
Финансирование
Supported by NIH grants CA 97193, CA 34944, CA 40360, HL 26490 and HL 34595 and an investigator-initiated grant from BASF Corporation. BASF, Wyeth Pharmaceuticals and DSM Nutritional Products had no role in the study design; conduct of the study; collection, management, analysis and interpretation of the data; or preparation, review or approval of the manuscript.
Поддержка в натуральной форме
Study agents and packaging provided by BASF Corporation (vitamin C, vitamin E, beta-carotene), Wyeth Pharmaceuticals (multivitamin) and DSM Nutritional Products.
Результат
Vitamin C 500 mg daily versus placebo, mean follow-up 8.0 years: major cardiovascular events in 619 of 7329 versus 626 of 7312 men (10.8 and 10.9 per 1000 person-years; HR 0.99, 95% CI 0.89 to 1.11); total mortality 857 versus 804 (HR 1.07, 0.97 to 1.18).
Консенсус
US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, Cabana M, Chelmow D, et al. Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer: US Preventive Services Task Force Recommendation Statement JAMA, 2022.
doi:10.1001/jama.2022.8970 PubMed 35727271
Финансирование и результат
Финансирование
The USPSTF is an independent, voluntary body; the US Congress mandates that the Agency for Healthcare Research and Quality (AHRQ) support its operations. AHRQ staff assisted in developing the research plan, commissioning the evidence review, coordinating expert review and public comment, and writing and preparing the statement; they had no role in approving the final statement or the decision to submit.
Результат
The USPSTF recommends against beta carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer (D recommendation), and concludes that the evidence is insufficient to assess the balance of benefits and harms of multivitamins and of single- or paired-nutrient supplements other than beta carotene and vitamin E (I statements).

Обновлено 2026-10-21