摘要
鈣是一種重要的礦物質，在人體健康，特別是骨骼健康中扮演著不可或缺的角色。海洋生物鈣是一種豐富的資源，其結構活性複雜且被廣泛接受。這篇綜述評估了海洋生物鈣在來源、鈣補充劑的使用、鈣的生物利用率以及海洋鈣的新應用方面的研究進展。同時，也探討了在生物醫學研究、製藥、保健和食品工業中融入海洋生物鈣產品的未來發展潛力。本綜述旨在提供有關海洋生物資源利用和產品開發的全面文獻記錄。
主題關鍵詞：營養學、天然產品
引言
鈣是一種重要的微量營養素，廣泛被認為影響骨骼健康和人體代謝。缺鈣可能引發骨質疏鬆、佝僂病、癲癇和貧血等問題。鈣通過食物或鈣補充劑進入循環系統，並在血液和骨骼鈣之間保持動態平衡【1】。鈣的主要來源是乳製品，包括牛奶及其副產品，如奶酪和煉乳，其次是穀物和豆腐等其他來源【2】。然而，不適當的飲食可能會降低鈣的生物利用率。例如，穀物中的植酸和綠葉蔬菜中的草酸可能導致鈣沉澱為植酸鈣和草酸鈣，這些是不溶性化合物【3】。在美國的一項研究發現，僅靠食物攝取礦物質和維生素的成年人中，約有 38% 的人鈣攝取不足，約 93% 的人維生素 D 攝取不足，而維生素 D 在鈣吸收率、骨骼恆定和骨修復中起關鍵作用【4】【5】。隨著年齡增長，缺鈣的情況逐漸惡化【6】。慢性缺鈣導致骨質疏鬆成為一種流行病【7】。越來越多的人面臨缺鈣及其相關疾病【8–10】。因此，越來越多的人根據醫生或媒體的建議，通過補充劑來增加鈣的攝取【11】。
這些補充劑的鈣來源包括碳酸鈣礦石、富含鈣的動物骨骼、海洋貝殼和甲殼類生物【12】。然而，天然碳酸鈣礦石可能含有有害元素，如重金屬【13】。動物骨骼則可能有傳播朊病毒的風險【14】【15】。近年來，由於其豐富的儲量、高安全性和生物活性，來自海洋的鈣補充劑越來越受到關注【16】【17】。隨著海洋資源的開發和利用，超過 50% 的漁業副產品（包括骨骼、魚鰭、魚頭和內臟）每年作為廢料被丟棄，而這些可以被有效利用。海洋礦物補充劑可能增加骨骼周轉率，有助於防止損傷並修復受損骨骼【18】。作為鈣的重要來源，使用海洋生物鈣是一種提高生物資源利用率的重要方式。本綜述全面評估了海洋鈣的來源、鈣補充劑製備的技術、海洋鈣的生物活性和生物利用率，為開發利用海洋鈣補充劑提供參考。
海洋鈣的來源
海洋中富含生物資源，而鈣是海洋生物的重要礦物成分。來自海洋的鈣主要來源於魚骨、貝類和甲殼類生物的外殼、珊瑚以及海藻（如圖 1 所示）。
來自魚骨的鈣
魚骨是指魚體中的軸骨、附肢骨和魚骨，約占魚體總重的 10–15%【19】。魚骨組織主要由有機的細胞外基質構成，並覆蓋著羥基磷灰石 [Ca₅(PO₄)₃OH]。相比於其他八種魚類，三文魚科魚類的鈣含量最低，而無脂乾物質中的鈣含量可高達 135–147 g/kg【20】。鯊魚軟骨是另一個重要的鈣來源。例如，膠鯊的下顎軟骨中的鈣主要以羥基磷酸鈣晶體 [Ca₁₀(PO₄)₆(OH)₂] 的形式存在，其鈣磷酸鹽含量在乾重基礎上可達 67%，範圍介於 124–258 g/kg【21】。大型魚類的魚骨需經化學和生物方法處理以破壞有機材料，或與膠原蛋白結合以提高鈣的溶解率，因為羥基磷灰石形式的鈣不易被人體吸收【22】。小型魚類如鳳尾魚和鱗鰭魚，其骨骼較柔軟，可製成即食食品，連同骨頭一起食用【23】。魚骨鈣的製備通常包括通過烹煮去除蛋白質和脂肪，使用鹼性和有機溶劑或酵素水解處理，並進行超細粉碎以獲得魚骨粉。
來自貝殼的鈣
貝殼約占貝類總質量的 60%，其碳酸鈣含量可高達 95%。貝殼是高品質海洋鈣的重要來源。貝類養殖為人類提供了一種低環境影響的可持續蛋白質來源【24】。2016 年，全球養殖貝類達到 1713.9 萬噸，占總漁業產量的 21.42%【25】。此外，由於貝殼中的鈣含量高於魚骨，其鈣的產量更大【26】【27】。研究了來自巨扇貝殼粉和化石貝殼粉的鈣補充劑的效果，結果表明這些天然鈣來源具有良好的溶解性和生物利用率【28】。貝殼鈣補充劑已在多個國家銷售，但貝殼資源的利用率仍然很低，其綜合開發和利用需要進一步支持。
來自甲殼類的鈣
人們可以通過食用小型乾蝦或螃蟹直接攝取鈣。甲殼類的加工和消費會產生 30–40% 的海洋資源廢料【29】。甲殼類主要由碳酸鈣 (CaCO₃)、幾丁質和蛋白質組成【30】。對蝦和蟹殼的研究主要集中於幾丁質和蛋白質資源的利用，而鈣有時作為副產品回收，例如氫磷酸鈣、乳酸鈣和鈣【31】。
來自珊瑚的鈣
珊瑚鈣來自多種生物的外骨骼。珊瑚鈣是一種天然的海洋鈣來源，含有 24% 的鈣、12% 的鎂以及超過 70 種礦物質。近年來，珊瑚鈣作為一種補鈣新趨勢，常被用於治療骨代謝紊亂、骨質疏鬆及其他骨骼疾病【33】【34】。
來自海藻的鈣
海藻，尤其是綠藻，富含多種礦物質，如鈣【35】。例如，Aquamin 是一種典型的富鈣補充劑，來自紅海藻 Lithothamnion 的鈣化骨骼遺骸，其鈣含量高達 31%【36】。一項研究表明，與碳酸鈣補充劑相比，海藻鈣對馬匹的鈣吸收效果更好【37】。研究還發現，從海藻提取的鈣在骨骼鈣化中具有有益的促進作用，尤其是在骨質疏鬆的動物模型中【38】。由牡蠣殼粉和海藻製備的藻鈣，其生物利用率高於碳酸鈣【39】。
鈣補充劑與生物利用率
直接攝取海洋來源的鈣
最常見的直接鈣補充劑包括小乾蝦、貝殼粉和小型魚類。若干海洋鈣補充劑（如牡蠣殼和珊瑚鈣）已在不同國家商業化。然而，來自這些海洋來源的主要成分是碳酸鈣和多羥基磷酸鈣，這些成分難以吸收且會增加胃部負擔【40】。為了提高鈣的吸收率，通常需要先將海洋來源粉碎或進行真空加熱處理【41】【42】。
研究發現，與碳酸鈣補充劑或其他富鈣食物相比，海洋來源的鈣具有一定優勢。例如，Aquamin 的生物利用率更高，且在減緩骨質流失方面優於碳酸鈣【36】。此外，魚骨粉 (Phoscalim) 和魟魚軟骨水解物 (Glycollagene) 在短期鈣吸收和骨吸收方面與牛奶相當【16】。用鱈魚骨製成的鈣片足以作為鈣補充劑並預防骨質疏鬆【43】。
目前，國際推薦的一般人群每日鈣攝取量為 700–1200 毫克。然而，青少年（9–18 歲）需要約 1300 毫克鈣，而低鈣飲食的孕婦則需要 1500–2000 毫克鈣【44】【45】。研究顯示，缺鈣人群中超過 50% 為 70 歲以上的男性和女性、51–70 歲的女性、9–13 歲的男孩和女孩，以及 14–18 歲的女孩【46】。意識性地補充海洋鈣對預防缺鈣非常有效，但直接從海洋生物中攝取鈣不足以治療缺鈣疾病。治療缺鈣疾病還需要選擇更高劑量的鈣補充劑或藥物【5】。
有機酸鈣
有機酸鈣（例如檸檬酸鈣、乳酸鈣、葡萄糖酸鈣、醋酸鈣、甲酸鈣和丙酸鈣）具有更高的生物利用率、溶解性和吸收率，無論胃內容物如何，因為它們對胃 pH 值的敏感性低於碳酸鈣【11】【40】【47】。有機酸鈣主要通過鈣化合物的中和或發酵製備而成（圖 2）。作為一種膳食鈣補充劑，甲酸鈣被發現比碳酸鈣和檸檬酸鈣具有顯著的優勢【48】。葡萄糖酸鈣被證明具有較高的相對生物利用率，並且比碳酸鈣更容易被人體耐受【49】。
然而，葡萄糖酸鈣和乳酸鈣的鈣濃度較低，因此作為口服補充劑並不實用。醋酸鈣和丙酸鈣也不廣泛使用【50】。單獨使用有機酸鈣對吸收效果並不理想，因為它們可能與食物中的草酸或植酸結合。將鈣與兩種或更多的有機酸結合，例如檸檬酸蘋果酸鈣 (CCM)【10】，或與牛膠原蛋白肽結合的檸檬酸鈣【51】【52】，則可以改善吸收效果。此外，聚醣（Polycan）與乳酸–葡萄糖酸鈣的結合使用，被發現相比單獨使用有機酸鈣具有有益的協同作用【53】【54】。
海洋來源的有機酸鈣主要包括魚骨、蝦殼、蟹殼和其他貝殼【3】。為了促進鈣的吸收，應根據營養成分和相關加工特性選擇適當的處理方法，例如焙燒、酵素水解和發酵方法【55】【56】。隨後，加入檸檬酸、葡萄糖酸、乳酸、醋酸和/或丙酸以製備有機酸鈣。經減壓處理後，貝類鈣與檸檬酸和乳酸結合的鈣的溶解性和生物利用率得到了提高【26】。魚骨可以與乳酸乳球菌 (Leuconostoc mesenteroides) 發酵以獲得高含量的可溶性鈣，包括游離鈣、鈣氨基酸、醋酸鈣、小肽鈣和乳酸鈣。草魚骨的發酵不僅可以提高鈣的生物利用率，還能避免魚骨鈣和水產蛋白的浪費【57】。
鈣螯合物
鈣螯合物是指氨基酸或肽與金屬鈣離子之間形成穩定鍵的金屬複合物，包括兩種主要產品：鈣氨基酸螯合物和鈣肽螯合物【58–60】。它主要通過多肽或寡肽與鈣離子螯合，或單一或複合氨基酸與鈣離子螯合製備而成（圖 3）。氨基酸螯合鈣不依賴於維生素 D3，並且可以通過氨基酸代謝被人體吸收。例如，賴氨酸鈣是一種新型的鈣製劑，可能具有更好的吸收效果，使其成為比碳酸鈣和檸檬酸蘋果酸鈣 (CCM) 更好的鈣補充劑【61】。
然而，肽螯合鈣相較於其他鈣補充劑具有更多優勢【62–64】。越來越多的螯合肽被發現能促進和改善礦物質的生物利用率【65】【66】。通過酵素水解將魚骨鈣與具有鈣結合能力的骨膠原肽結合製備的鈣肽螯合物，顯示出顯著的鈣生物利用率提升【67–69】。基於藻類肽的鈣螯合複合物和藻酸鈣納米顆粒被認為具有作為鈣補充劑以改善骨骼健康的潛力【70–72】。
然而，肽螯合鈣的生產成本高，產量低。隨著新型製備技術的發展，肽螯合鈣有可能成為一種優良的鈣補充劑。
海洋來源鈣的其他功能
生物活性
海洋生物鈣除了改善鈣的恆定和骨骼健康外，還具有其他生物功能。例如，研究表明珊瑚鈣能調節血壓並預防結腸癌的轉移【30】【73】【74】。來自螺旋藻（Spirulina platensis，一種藍綠藻）中的螺旋藻鈣螯合物被證明能有效抑制單純皰疹病毒1型 (HSV-1)，並可能對其他皰疹病毒感染有抑制作用【75】。珊瑚鈣氫氧化物具有抗氧化作用，在小鼠中可延緩衰老並預防肝臟脂肪變性【76–78】。來自扇貝殼的氧化鈣能抑制假單胞菌（Pseudomonas aeruginosa），該細菌是引起雞蛋腐敗的致病菌，並且對化學試劑（如消毒劑和清潔劑）有很強的抗性【79】。來自牡蠣的鈣在抑制口腔鱗狀細胞癌的形成和增殖方面表現出良好的效果【80】。
新材料
來自海洋的鈣可以作為高附加值化合物的原材料，應用於生物醫學研究、製藥、保健和食品工業【81】。研究表明，牡蠣殼、蛤殼、烏賊骨和鮭魚骨具有生產多孔支架的巨大潛力【82–85】。這些支架的結構特性有助於改善生物活性，包括機械性能、骨組織生長和血管化【86】。從鮭魚骨和虹鱒骨中提取的天然羥基磷灰石 (nHAP) 在骨組織工程中作為骨植入材料替代品展現了巨大潛力【87】。海洋生物鈣還可用於製備吸附材料，在水處理中表現出廣泛的應用潛力。例如，由蟹殼製成的富鈣生物炭可用於去除廢水中的染料和磷【88】【89】。由牡蠣殼合成的不溶性矽酸鈣水合物可用於去除有機污染物和重金屬離子【90】。從大西洋鱈魚骨中提取的單相羥基磷灰石 (HA) 和雙相磷酸鈣 (HA/β-TCP) 無已知的細胞毒性，在模擬體液中顯示出良好的生物活性【91】。因此，從海洋生物提取的磷酸鈣在製備抗細菌感染的骨替代材料或骨缺損修復方面具有良好的前景。從鱈魚骨中提取的羥基磷灰石 (Ca10(PO4)6(OH)2, HAp) 作為一種鈣磷酸鹽，是防曬配方中更安全的選擇，顯示其在保健品和化妝品中的廣泛應用潛力【92】。
食品添加劑
來自海洋加工廢料的生物鈣仍可用於食品加工。例如，魚骨可以添加到魚糜中以改善產品的凝膠性能【93】。牡蠣殼鈣粉可以提高重組火腿的咀嚼性和彈性【94】。富含鈣的蝦殼和蟹殼也可以用來製備食品絮凝劑【95】。許多食品添加劑含有鈣，例如碳酸鈣、矽酸鈣、硫酸鈣和乳酸鈣。由海洋生物製得的鈣添加劑因其天然來源可能更安全。
結論與未來展望
海洋加工廢料通常被視為無用，但它是一種豐富且低成本的鈣來源。一項研究發現，55 種鈣補充劑品牌可根據其主要成分分為七類，其中三類或更多來自海洋生物，主要包括牡蠣/蛤殼、海藻、鯊魚軟骨和螯合鈣產品（表 1）【10】。此外，來自海洋生物的鈣具有良好的生物利用率和生物功能。重新利用海洋生物的副產品不僅可以增加鈣的附加價值，還能減少環境污染的風險。
在鈣補充劑的開發中，未來的工作應集中於海洋生物中蛋白質、膠原蛋白、幾丁質、鈣及其他營養成分的綜合利用，以及利用特定活性成分來提高鈣的生物利用率。在其他應用方面，研究可能需要關注將海洋鈣轉化為健康食品、新材料或食品添加劑的過程，並將其擴展到商業規模。
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