Vitamin A

CARLSBAD, Calif.--(BUSINESS WIRE)--Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the “Company”) today reported financial results and provided key updates for the second quarter ended June 30, 2025. “During the second quarter, we continued to build momentum across our business,” said Brett P. Monia, Ph.D., chief executive officer of Ionis. “Our strong performance included excellent commercial execution, resulting in a substantial increase in TRYNGOLZA revenues, our first independently launched medicine. We expect additional advancements in the second half, including Ionis’ second independent launch with donidalorsen for hereditary angioedema, anticipated next month, and important Phase 3 results for olezarsen in severe hypertriglyceridemia and zilganersen in Alexander disease. We believe these four programs collectively represent multi-billion-dollar revenue potential and a transformational opportunity for Ionis and for patients.” Second Quarter 2025 Summary Financial Results(1): Three months ended Six months ended June 30, June 30, 2025 2024 2025 2024 (amounts in millions) Total revenue $452 $225 $584 $345 Operating expenses $312 $291 $591 $560 Operating expenses on a non-GAAP basis $282 $260 $532 $498 Income (loss) from operations $140 ($66) ($7) ($215) Income (loss) from operations on a non-GAAP basis $170 ($35) $52 ($153) (1) Reconciliation of GAAP to non-GAAP basis contained later in this release. Recent Financial Highlights Revenue doubled in the second quarter of 2025 and increased nearly 70% in the first half compared to the same period last year, driven by the continued successful launch of TRYNGOLZA and increased royalty and R&D revenues Operating expenses increased by single digits in the second quarter and first half of 2025, compared to the same periods last year, primarily due to investments related to commercialization efforts for TRYNGOLZA, donidalorsen and WAINUA Increased 2025 financial guidance reflects an improved outlook for the full year, strong overall revenue performance experienced year-to-date, including the early strength in TRYNGOLZA revenues: Full Year 2025 Guidance Previous Guidance New Guidance Total Revenue $725-750 million $825-850 million TRYNGOLZA product sales, net Not provided $75-80 million Operating loss on a non-GAAP basis <$375 million $300-325 million Cash, cash equivalents and short-term investments ~$1.9 billion ~$2.0 billion Second Quarter 2025 Financial Results “For the second time this year, we are significantly raising our 2025 financial guidance — this time driven by an improved outlook for the year and strong revenue performance to date, which includes the early launch excellence with TRYNGOLZA. In addition to strong commercial performance, our second quarter results included the substantial revenue we earned from licensing sapablursen, a medicine outside our core areas of focus. We are in a strong financial position, with a commitment to drive operating leverage as we continue executing on our strategic priorities,” said Elizabeth L. Hougen, chief financial officer, Ionis. “Moving forward, the three additional independent launches anticipated over the next eighteen months, including donidalorsen for hereditary angioedema, olezarsen in severe hypertriglyceridemia and zilganersen in Alexander disease, position Ionis to deliver substantial and growing product revenue. This product revenue, coupled with anticipated increasing royalty revenue from multiple partner launches, along with disciplined investment, position Ionis to achieve sustained growth and positive cash flow in the next few years.” Recent Highlights - Wholly Owned Medicines TRYNGOLZA TM (olezarsen), the first and only FDA approved treatment for adults living with familial chylomicronemia syndrome (FCS) as an adjunct to diet Generated net product sales of $19 million in the second quarter of 2025, its second full quarter on the market, and $26 million in the first half of 2025 Received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), paving the way to bring TRYNGOLZA to patients across Europe Generated net product sales of $19 million in the second quarter of 2025, its second full quarter on the market, and $26 million in the first half of 2025 Received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), paving the way to bring TRYNGOLZA to patients across Europe Olezarsen on track for topline Phase 3 data from pivotal CORE and CORE2 studies in patients with sHTG in September 2025, positioning olezarsen to potentially treat this second, more prevalent patient population with high unmet need Announced positive topline results from the Essence study in people with moderately elevated triglycerides; achieved primary and all key secondary endpoints for 80 mg and 50 mg monthly doses with favorable safety and tolerability Announced positive topline results from the Essence study in people with moderately elevated triglycerides; achieved primary and all key secondary endpoints for 80 mg and 50 mg monthly doses with favorable safety and tolerability Donidalorsen on track to launch this year, assuming approval, with a U.S. PDUFA date of August 21, 2025 Poised to transform the treatment paradigm for individuals with hereditary angioedema (HAE) as the first and only RNA-targeted prophylactic therapy that has the potential to offer durable efficacy, a favorable safety and tolerability profile, and the longest available dosing interval, with self-administration via autoinjector monthly or every other month Donidalorsen is currently under regulatory review in the EU Poised to transform the treatment paradigm for individuals with hereditary angioedema (HAE) as the first and only RNA-targeted prophylactic therapy that has the potential to offer durable efficacy, a favorable safety and tolerability profile, and the longest available dosing interval, with self-administration via autoinjector monthly or every other month Donidalorsen is currently under regulatory review in the EU First patient dosed in the Phase 3 REVEAL study of ION582, an investigational medicine for the treatment of people living with Angelman syndrome (AS), a serious and rare neurodevelopmental disorder Recent Highlights – Partnered Medicines WAINUA TM (eplontersen) (WAINZUA in EU) for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) continues to perform well, achieving several important commercial milestones: Generated sales of $44 million and $84 million resulting in royalty revenue of $10 million and $20 million in the second quarter and first half of 2025, respectively New launches underway in numerous regions, including the EU; additional submissions in progress to expand WAINUA access globally Generated sales of $44 million and $84 million resulting in royalty revenue of $10 million and $20 million in the second quarter and first half of 2025, respectively New launches underway in numerous regions, including the EU; additional submissions in progress to expand WAINUA access globally SPINRAZA ® (nusinersen) for the treatment of spinal muscular atrophy (SMA) generated global sales of $393 million and $817 million resulting in royalty revenue of $54 million and $102 million in the second quarter and first half of 2025, respectively Higher dose nusinersen under review for marketing approval in the U.S. (PDUFA date of September 22, 2025) and in the EU Higher dose nusinersen under review for marketing approval in the U.S. (PDUFA date of September 22, 2025) and in the EU Biogen to advance salanersen (formerly ION306/BIIB115), an investigational medicine for SMA into registrational studies based on positive interim Phase 1 results; developed using novel Ionis antisense chemistry with the potential to achieve high efficacy and annual dosing Phase 1 data with salanersen in SMA patients showed substantial slowing of neurodegeneration and clinically meaningful improvements in patients previously treated with gene therapy Phase 1 data with salanersen in SMA patients showed substantial slowing of neurodegeneration and clinically meaningful improvements in patients previously treated with gene therapy AstraZeneca initiated the Phase 2b study of opemalirsen (formerly ION532/AZD2373), an investigational medicine designed to reduce the production of apolipoprotein L1 (APOL1) for the treatment of APOL1-mediated kidney disease (AMKD) triggering a $30 million milestone payment to Ionis Corporate Updates In June 2025, Ionis announced that Richard Geary, Ph.D., executive vice president and chief development officer, will retire effective January 2026 and that Holly Kordasiewicz, Ph.D., currently senior vice president, neurology, will succeed him in the role Revenue Ionis’ revenue was comprised of the following: Three months ended Six months ended June 30, June 30, 2025 2024 2025 2024 Revenue: (amounts in millions) Commercial revenue: Product sales, net: TRYNGOLZA sales, net $19 $- $26 $- Total product sales, net 19 - 26 - Royalty revenue: SPINRAZA royalties 54 57 102 95 WAINUA royalties 10 4 20 5 Other royalties 6 3 12 13 Total royalty revenue 70 64 134 113 Other commercial revenue: TEGSEDI and WAYLIVRA revenue, net 14 8 19 17 Other revenue - - - 2 Total commercial revenue 103 72 179 132 Research and development revenue: Collaborative agreement revenue 337 141 382 191 WAINUA joint development revenue 12 12 23 22 Total research and development revenue 349 153 405 213 Total revenue $452 $225 $584 $345 Commercial revenue for the second quarter and first half of 2025 increased 43% and 36% respectively, compared to the same periods in 2024. This increase was driven by TRYNGOLZA product sales. Higher royalty revenue also contributed to the year over year increase. The remainder of the Company’s revenue came from programs under its R&D collaborations, including a $280 million upfront payment for the global license of sapablursen to Ono Pharmaceutical Co., Ltd., reflecting the value that Ionis’ pipeline and technology continues to generate. Operating Expenses SG&A expenses increased as anticipated for the second quarter and first half of 2025, compared to the same periods in 2024, primarily due to the launches of TRYNGOLZA and WAINUA, and advancing launch preparation activities for donidalorsen. This increase was partially offset by a decrease in R&D expenses as several late-stage studies ended. Overall, this led to a modest year-over-year increase in total operating expenses. Balance Sheet As of June 30, 2025, Ionis’ cash, cash equivalents and short-term investments were $2.3 billion, consistent with December 31, 2024. Ionis received $280 million from the global license of sapablursen in the second quarter of 2025. Ionis’ working capital decreased over the same period primarily due to the reclassification of the Company’s 0% convertible notes as a current liability. Webcast and Other Updates Management will host a conference call and webcast to discuss Ionis’ second quarter 2025 results at 11:30 a.m. Eastern time on Wednesday, July 30, 2025. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address. To access the Company’s second quarter 2025 earnings slides click here. Ionis will be initiating a quiet period starting July 31, 2025, as the Company plans to announce the topline results from both the CORE and CORE2 studies simultaneously. The quiet period will be lifted upon the data announcement, expected in September. Ionis’ Marketed Medicines INDICATION for TRYNGOLZA™ (olezarsen) TRYNGOLZA™ (olezarsen) was approved by the U.S. Food and Drug Administration as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS TRYNGOLZA is contraindicated in patients with a history of serious hypersensitivity to TRYNGOLZA or any of the excipients in TRYNGOLZA. Hypersensitivity reactions requiring medical treatment have occurred. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Hypersensitivity reactions (including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills and myalgias) have been reported in patients treated with TRYNGOLZA. Advise patients on the signs and symptoms of hypersensitivity reactions and instruct patients to promptly seek medical attention and discontinue use of TRYNGOLZA if hypersensitivity reactions occur. ADVERSE REACTIONS The most common adverse reactions (incidence >5% of TRYNGOLZA-treated patients and >3% higher frequency than placebo) were injection site reactions, decreased platelet count and arthralgia. Please see full Prescribing Information for TRYNGOLZA. INDICATION for WAINUA™ (eplontersen) WAINUA injection, for subcutaneous use, 45 mg is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. IMPORTANT SAFETY INFORMATION for WAINUA™ (eplontersen) WARNINGS AND PRECAUTIONS Reduced Serum Vitamin A Levels and Recommended Supplementation WAINUA leads to a decrease in serum vitamin A levels. Supplement with recommended daily allowance of vitamin A. Refer patient to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency occur. ADVERSE REACTIONS Most common adverse reactions (≥9% in WAINUA-treated patients) were vitamin A decreased (15%) and vomiting (9%). Please see link to U.S. Full Prescribing Information for WAINUA. For more information about SPINRAZA and QALSODY, visit https://www.spinraza.com/ and https://www.qalsody.com/, respectively. QALSODY is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY. Continued approval may be contingent upon verification of clinical benefit in confirmatory trial(s). About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionis.com and follow us on X (Twitter), LinkedIn and Instagram. Ionis’ Forward-looking Statement This press release includes forward-looking statements regarding Ionis’ business, financial guidance and the therapeutic and commercial potential of our commercial medicines, additional medicines in development and technologies. Any statement describing Ionis’ goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2024, and most recent Form 10-Q, which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company. In this press release, unless the context requires otherwise, “Ionis,” “Company,” “we,” “our” and “us” all refer to Ionis Pharmaceuticals and its subsidiaries. IONIS® is a registered trademark of Ionis Pharmaceuticals, Inc. TRYNGOLZA® is a registered trademark of Ionis Pharmaceuticals, Inc. AKCEATM is a trademark of Akcea Therapeutics, Inc. TEGSEDITM is a trademark of Akcea Therapeutics, Inc. WAYLIVRATM is a trademark of Akcea Therapeutics, Inc. SPINRAZA® and QALSODY® are registered trademarks of Biogen. WAINUA® is a registered trademark of the AstraZeneca group of companies. IONIS PHARMACEUTICALS, INC. SELECTED FINANCIAL INFORMATION Condensed Consolidated Statements of Operations (In Millions, Except Per Share Data) Three months ended Six months ended June 30, June 30, 2025 2024 2025 2024 (unaudited) Revenue: Commercial revenue: Product sales, net $19 $- $26 $- Royalty revenue 70 64 134 113 Other commercial revenue 14 8 19 19 Total commercial revenue 103 72 179 132 Research and development revenue: Collaborative agreement revenue 337 141 382 191 WAINUA joint development revenue 12 12 23 22 Total research and development revenue 349 153 405 213 Total revenue 452 225 584 345 Expenses: Cost of sales 4 4 6 6 Research, development and patent 217 222 418 436 Selling, general and administrative 91 65 167 118 Total operating expenses 312 291 591 560 Income (loss) from operations 140 (66) (7) (215) Other income (expense): Interest expense related to the sale of future royalties (19) (18) (37) (36) Other income, net 3 18 21 42 Income (loss) before income tax benefit (expense) 124 (66) (23) (209) Income tax benefit (expense) - - - - Net income (loss) $124 ($66) ($23) ($209) Basic net income (loss) per share $0.78 ($0.45) ($0.15) ($1.43) Diluted net income (loss) per share $0.70 ($0.45) ($0.15) ($1.43) Shares used in computing basic net income (loss) per share 159 146 159 146 Shares used in computing diluted net income (loss) per share 182 146 159 146 IONIS PHARMACEUTICALS, INC. Reconciliation of GAAP to Non-GAAP Basis: Condensed Consolidated Operating Expenses, Income (Loss) From Operations, and Net Income (Loss) (In Millions) Three months ended June 30, Six months ended June 30, 2025 2024 2025 2024 (unaudited) As reported research, development and patent expenses according to GAAP $217 $222 $418 $436 Excluding compensation expense related to equity awards (20) (23) (40) (45) Non-GAAP research, development and patent expenses $197 $199 $378 $391 As reported selling, general and administrative expenses according to GAAP $91 $65 $167 $118 Excluding compensation expense related to equity awards (10) (8) (19) (17) Non-GAAP selling, general and administrative expenses $81 $57 $148 $101 As reported operating expenses according to GAAP $312 $291 $591 $560 Excluding compensation expense related to equity awards (30) (31) (59) (62) Non-GAAP operating expenses $282 $260 $532 $498 As reported income (loss) from operations according to GAAP $140 ($66) ($7) ($215) Excluding compensation expense related to equity awards (30) (31) (59) (62) Non-GAAP income (loss) from operations $170 ($35) $52 ($153) As reported net income (loss) according to GAAP $124 ($66) ($23) ($209) Excluding compensation expense related to equity awards and related tax effects (30) (31) (59) (62) Non-GAAP net income (loss) $154 ($35) $36 ($147) Reconciliation of GAAP to Non-GAAP Basis As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP income (loss) from operations, and non-GAAP net income (loss) were adjusted from GAAP to exclude compensation expense related to equity awards and the related tax effects. Compensation expense related to equity awards are non-cash. These measures are provided as supplementary information and are not a substitute for financial measures calculated in accordance with GAAP. Ionis reports these non-GAAP results to better enable financial statement users to assess and compare its historical performance and project its future operating results and cash flows. Further, the presentation of Ionis’ non-GAAP results is consistent with how Ionis’ management internally evaluates the performance of its operations. IONIS PHARMACEUTICALS, INC. Condensed Consolidated Balance Sheets (In Millions) June 30, December 31, 2025 2024 (unaudited) Assets: Cash, cash equivalents and short-term investments $2,290 $2,298 Contracts receivable 53 92 Other current assets 235 230 Property, plant and equipment, net 112 94 Right-of-use assets 164 162 Other assets 131 127 Total assets $2,985 $3,003 Liabilities and stockholders’ equity: Current portion of deferred contract revenue $76 $79 0% convertible senior notes, net – current 630 - Other current liabilities 191 229 1.75% convertible senior notes, net 566 565 0% convertible senior notes, net - 629 Liability related to sale of future royalties, net 541 542 Long-term lease liabilities 164 162 Long-term obligations, less current portion 60 52 Long-term deferred contract revenue 125 157 Total stockholders’ equity 632 588 Total liabilities and stockholders’ equity $2,985 $3,003 Key 2025 and 2026 Value Driving Events(1) New Product Launches Program Indication 2025 2026 Donidalorsen (U.S.) HAE • TRYNGOLZA (U.S.) FCS Achieved WAINZUA (EU) ATTRv-PN Achieved Olezarsen (U.S.) sHTG • Zilganersen (U.S.) Alexander disease • Regulatory Actions Program Indication Regulatory Action 2025 2026 Donidalorsen HAE U.S. approval decision • EU approval decision • TRYNGOLZA FCS EU approval decision • Olezarsen sHTG U.S. submission • U.S. approval decision • Zilganersen Alexander disease U.S. submission • U.S. approval decision • Nusinersen (higher dose) SMA U.S. and EU submissions Achieved U.S. approval decision • WAINZUA ATTRv-PN EU approval decision Achieved Pelacarsen Lp(a)- CVD U.S. submission • Bepirovirsen HBV Regulatory submission(s) • Regulatory decision(s) • Key Phase 3 Clinical Events Program Indication Event 2025 2026 Olezarsen sHTG CORE, CORE2 data • Essence data Achieved Zilganersen Alexander disease Phase 3 data • ION582 Angelman syndrome Phase 3 study start Achieved Phase 3 enrollment completion • Pelacarsen Lp(a)-CVD Lp(a) HORIZON data • Bepirovirsen HBV B-Well data • Eplontersen ATTR-CM CARDIO-TTRansform data • Sefaxersen IgAN IMAGINATION data • Ulefnersen FUS-ALS FUSION data • (1) Timing expectations based on current assumptions and subject to change. Indicates that the milestone is anticipated in the respective year.

自古以来，抵御疾病、强健体魄就是人类不懈的追求，为此，我们塑造了“正气”、“元气”等概念，也尝试了各种方法，试图为我们的身体筑起防御高墙。神医华佗创编“五禽戏”，模仿动物动作以疏通经络、强身健体，本质上是一场古老的“免疫力提升”的实践。古人寻访仙草灵药，熬制滋补汤剂，也多是期盼能扶正祛邪，百病不侵。时光流转至今日，现代流行病学研究表明，30-50岁成年人每年都会经历2-3次感冒。仅在中国，每年报告的流感样疾病就约340万例，导致每年估计流感相关死亡人数高达88,100例。1应对日常中常见的感冒和流感，“免疫力”这面盾牌是否足够坚固？我们投入的种种努力，效果究竟如何？现代人提升免疫力的武器库已空前丰富，但“经典”选手——我们日常服用的复合维生素矿物质制剂(MVM)——正又进入科研界的视野，并带来令人瞩目的新研究发现。2025年7月19日，中国医学科学院北京协和医院临床营养科的科研人员在亚太临床营养学会 (Asia Pacific Clinical Nutrition Society, APCNS) 官方期刊《亚太临床营养学杂志(英文版)》(Asia Pacific Journal of Clinical Nutrition, APJCN)中发表了一项基于中国人群大规模真实世界研究，发现了复合维生素矿物质制剂(MVM)全新健康作用。1这项研究在2024年4月-7月期间，纳入了全国18省份3415名社区居民（MVM组1,549名，对照组1,866名），经倾向性评分匹配（PSM）后，两组各保留1,130人，人口学特征均衡。评估了常规使用复合维生素矿物质补充剂（MVM）对中国人群中急性上呼吸道感染（AURIs）包括感冒和流感的流行率和症状严重性的影响。其研究结果令人振奋：MVM组的AURIs期间发生率显著低于对照组，（31.7%比44.8%，P<0.001）。对于年龄≥45岁的参与者保护效应最强（OR=0.407，P <0.001）。即：规律服用至少三个月复合维生素矿物质补充剂，可显著降低中国人群感冒和流感的发生达42.8%，对年龄≥45岁人群的保护作用更为突出。在感冒和流感的症状方面，复合维生素矿物质显著减少感冒和流感的鼻塞、喉咙痛、头痛、腹泻、打喷嚏、疲乏症状。研究同时还发现规律服用复合维生素和矿物质的人群，ISQ免疫评分普遍高于未服用人群。既往研究的MVM配方异质性导致结果可行性差。1本研究采用标准化MVM制剂: 多维元素片29/29-Ⅱ（OTC，商品名“善存/银善存”），由赫力昂生产制造。 这项2025年新研究首次基于中国社区大样本证实MVM对AURIs的预防作用，为我们理解营养补充与免疫力、上呼吸道感染的关系，打开了新视角，也为大众日常抵抗并管理感冒和流感症状，为公共卫生干预提供了循证依据。 “日常营养”进阶“防感先锋” 近年来，复合维生素补充剂在免疫领域的价值日益凸显。本研究更进一步，将复合维生素矿物质日常补充与显著降低普通感冒/流感症状的患病率和症状严重性建立起明确关联，这项回顾性的真实世界研究是在中国的社区人群中进行的。并且采用倾向评分匹配（PSM）方法以1:1比例匹配样本，增加了MVM组和对照组的可比性；分析包括未匹配和匹配数据集，使用广义线性模型（GLMs）评估组间差异。 防的更好，缓解8大症状 这项研究显示，在相似生活环境下，规律补充复合维生素和矿物质（MVM）的中国人群，其抵御普通感冒和流感的能力显著提升，感染风险降低了42.8%(OR=0.572, p<0.001)。1这意味着，MVM可能有效增强了中国人群的“免疫韧性”，为健康防线提供了循证医学证据。即使不小心“中招”，补充MVM还能缓解8大流感感冒症状。研究发现，对照组报告的重度症状的期间发生率比例更高，而MVM组报告的轻微症状的期间发生率高于对照组，在轻微发热（81.6% vs. 74.7%，P =0.037）、轻微流鼻涕（74.4% vs. 68.0%，P =0.031）、轻微鼻塞（71.8% vs. 63.6%，P =0.011）、轻微喉咙痛（72.7% vs. 64.2%，P =0.005）、轻微咳嗽（73.0% vs. 65.8%，P =0.009）、轻微打喷嚏（82.2% vs. 74.0%，P =0.009）、轻微肌肉疼痛（82.0% vs. 72.9%，P =0.014）和轻微疲劳（74.7% vs. 68.6%，P =0.045）等症状上均存在统计学显著差异。1这也就意味着，在缓解以上8种症状上，复合维生素矿物质又立下了“大”功！同样重要的是，研究使用专门的免疫评分（ISQ）发现，MVM组免疫状态问卷（ISQ）评分≥6的参与者比例较高（95.9%比90.7%，OR=1.79，P<0.001）。1这提示我们，MVM的摄入可能有助于优化身体的整体免疫功能状态，让免疫系统处于更佳的“备战”水平。研究同时收集了受试者的饮食和运动数据，包括每日蔬菜、肉类、水产品、水果、牛奶或豆浆的摄入量、饮酒频率和身体锻炼的情况。在MVM组和对照组之间存在基线差异的情况下，通过采用倾向评分匹配（PSM）方法，使得这些差异得以最小化，这种方法有效减少了与生活方式因素相关的潜在偏移，从而增强了该研究结果的科学可信性。人体免疫系统的三道防线微量营养素，包括维生素和矿物质，在免疫反应的每个阶段都起着关键作用。当病原体入侵时，首先启动的是第一道防线，即物理化学屏障，包括皮肤、粘膜和体液等，它们能阻挡病原体进入体内。维生素A、D、C、B6、B9（叶酸）、B12以及矿物质锌和铁等，是构建和修复这道物理屏障、保持其健康功能的核心营养素。2若病原体突破这道屏障，第二道防线（非特异性免疫）便会启动，在病原体入侵的0-4h，会触发先天固有免疫应答，维生素A、D、C、E、B6、B9、B12、铁、锌、铜、硒、镁等维生素矿物质促进了固有免疫细胞的增殖、分化、效应功能及迁移，固有的免疫应答分为固有免疫细胞反应，包括巨噬细胞、NK细胞和中性粒细胞；以及固有免疫生化物质，包括抗菌肽和抗菌蛋白、补体、血清游离模式识别受体。在免疫应答的过程中会产生有害的“活性氧”。维生素C、E以及铁、锌、铜、硒、镁等矿物质会作为抗氧化剂和抗炎因子，帮助清除这些有害物质，防止过度的组织损伤；维生素A、D、C、铁、铜、硒则直接参与杀伤病原体（“抗菌效应”）。在病原体入侵后的4-96h，会产生炎症反应，导致血管舒张，血管通透性增加，炎性调节主要由维生素A、D、C、E、B6、B9、B12、锌、铜、硒、镁控制，炎症介质释放等有助于启动适应性免疫。2在病原体入侵超过96h后，第三道防线：适应性免疫应答（特异性）也会参与其中。树突状细胞（DC）会捕获病原体抗原，将其“呈递”给T淋巴细胞，促使T淋巴细胞活化并分化为不同类型的辅助性T细胞（主要是TH1和TH2）。维生素A、D、C、E、B6、B12、铁、锌、铜、硒在其中发挥了重要的作用。细胞免疫由TH1主导， TH1细胞分泌特定的细胞因子，激活巨噬细胞等抗原呈递细胞（APC），直接杀伤被感染的细胞。维生素A、D、C、E、B6、B9、B12、铁、锌、铜、硒促进了以细胞为介导的免疫反应；体液免疫由TH2主导，TH2细胞辅助B细胞增殖并分化成浆细胞，后者产生针对特定病原体的“抗体”（免疫球蛋白）。在这个过程中，维生素A、D、C、E、B6、B9、B12、锌、铜、硒、镁等维生素矿物质促进了抗体的产生与效应功能。3复合维生素矿物质：你的免疫力小帮手，全球多项研究来撑腰！不仅是中国，世界范围内对于复合维生素矿物质也展开了研究，在面对传染性更强的COVID-19新冠病毒时，MVM也是一面可靠的“屏障”。在2021年发表的一项涉及超过44.5万名来自英国、美国和瑞典的COVID-19症状研究应用用户的观察性研究中，研究发现服用复合维生素矿物质与降低新冠病毒（SARS-CoV-2）感染风险之间存在显著关联。在这项研究里，服用复合维生素补充剂的人群具有适度的保护效应，在整个英国人群中，检测阳性SARS-CoV-2的风险降低了13%，在美国人群中降低了12%，在瑞典人群中降低了22%。3针对不同人群，复合维生素矿物质制剂在提升免疫指标方面已有多项研究支持。河南省疾控中心发表于《营养学报》(2006)的一项研究关注中老年人补充多种营养素后的营养与免疫状态变化，结果发现，实验组的体液免疫指标（血清IgA、IgG、IgM 水平）均高于对照组，提示这类营养补充有助于增强体液免疫功能。4而在另一项聚焦2型糖尿病患者的研究中，来自解放军总医院营养科发表于《营养学报》(2010)的研究发现，补充微量营养素后，这类患者外周血中的淋巴细胞、CD4+细胞数量明显上升，CD8+细胞的升高受到抑制，CD4+/CD8+比例提升，意味着整体免疫系统更具抗感染能力。5此外，由复旦大学公共卫生学院发表于《环境与职业医学》(2004)的一项研究针对40~65岁人群的研究也显示，适量补充微量营养素可能有助于维持和改善自然杀伤（NK）细胞的活性，从而在一定程度上减缓免疫系统的衰老过程。6总而言之，随着国内外复合维生素矿物质的研究不断开展和发表，研究者们逐渐揭示出它们的潜在的提示免疫力并抵御感冒流感等的益处，这些不起眼的“基础微量营养素”，没有昂贵的价格标签，但在每天日常生活中用温和的方式，帮我们守护免疫健康，抵御常见上呼吸道感染疾病(感冒、流感)侵袭。参考文献：1. F Wang, et al. Multivitamin-mineral supplementation prevents acute upper respiratory tract infections[J]. Asia Pac J Clin Nutr 2025;34(4):596-609. https://apjcn.qdu.edu.cn/34_4_596.pdf 2. Gombart AF, et al. Nutrients. 2020 Jan 16;12(1):236. 3. Louca P, et al. BMJ Nutr Prev Health. 2021 Apr 19;4(1):149-157.4. 张丁,等. 营养学报 . 2006;28(4) :329-331.5. 景洪江,等. 营养学报 . 2010;32(1) :11-16.6. 郭红卫,等. 环境与职业医学 . 2004;21 (05) :374-376.免责声明：本文仅作最新前沿信息交流之目的，仅供医疗卫生行业专业人士阅读参考，文中所有观点不代表梅斯医学立场，亦不代表梅斯医学支持或反对文中观点。如需获得治疗方案指导，请前往正规医院就诊！