Abstract
The bioavailability of vitamin C, or ascorbic acid, depends on limiting transport mechanisms that may be bypassed by liposome-encapsulation. The goal for this study was to evaluate the uptake, antioxidant, and immune-modulating effects of liposome-encapsulated vitamin C (LEC) using Lypo-Spheric® technology, compared to three controls: ascorbic acid (AA), the phospholipid fraction composing the liposome, and placebo. A double-blinded placebo-controlled cross-over study design involved twelve healthy participants attending four clinic visits. At each visit, a baseline blood draw was performed, followed by consumption of 1 g LEC, 1 g AA, the phospholipid component of LEC, or placebo. Additional blood draws were performed at 2, 4, and 6 h. Consuming LEC and AA increased blood levels of vitamin C; the levels were significantly higher after consuming LEC at all timepoints when compared to AA (p < 0.01). LEC consumption increased serum antioxidant capacity (p < 0.01 at 2 h) and protection. Consuming LEC increased IFN-γ levels at 6 h, while consuming the phospholipid fraction rapidly decreased inflammatory cytokines IL-6, MCP-1, and MIP-1α at 2 h. Consuming LEC provided enhanced vitamin C bioavailability and antioxidant protection compared to AA. Consuming the phospholipids had anti-inflammatory effects. The results suggest that LEC provides antioxidant and immune benefits above AA, useful in preventive medicine.
1. Introduction
Vitamin C, or ascorbic acid, is a water-soluble essential nutrient that plays many pivotal roles in human health. Humans lack the biosynthetic machinery to produce vitamin C and therefore must obtain it from external sources, such as fruits, vegetables, organ meat, and supplements [1], with the challenge that its absorption depends on rate-limiting transport mechanisms. This has led to an increased interest in mechanisms to enhance the absorbance of this vitamin by delivering the vitamin encapsulated in liposomes.
Vitamin C acts as an antioxidant, scavenging free radicals and mitigating oxidative damage to cellular components [2]. Our body is constantly challenged by oxidative stress from our normal metabolic pathways, as well as exogenous oxidative stressors in the form of pathogens, pollutants, and UV radiation from the sun. Exogenous antioxidants, like vitamin C, aid endogenous free radical scavengers and help maintain redox balance within cells, mitochondria [3], and in the tissue microenvironment, which is fundamental for preventing damage to cellular components.
The antioxidant properties of vitamin C contribute to neuroprotection by scavenging damaging free radicals generated during synaptic activity and neuronal metabolism [4,5]. Studies in mice have demonstrated its support of cognitive function and memory when administered prior to experimental neuroinflammation induced by a bacterial toxin [6] and that it is an effective tool in supporting brain health by reducing damage after injury [7,8]. While research is limited in humans, vitamin C administration was shown to reduce the length of stay in intensive care and risk of mortality in traumatic-brain-injury patients [9].
Multiple enzymes involved in immune health, as well as for collagen synthesis, which is essential for the structural integrity and stability of the extracellular matrix [10], rely on vitamin C as a cofactor. This translates to many additional benefits of this vitamin in tissue integrity [11], delayed aging [12], and resistance to tissue disruption by wounding [13], infectious agents, and transformed cells [14,15].
Bioavailability is relevant when considering the effects of vitamin C since it cannot be produced endogenously. It is a water-soluble substance, and excess unabsorbed material is efficiently and quickly excreted [16]. Therefore, the dose and timing are critical when considering vitamin C uptake [17]. When vitamin C is consumed, several transport mechanisms facilitate the uptake from the gut lumen across the gut epithelium into blood plasma, where it then circulates throughout the body, available for cellular uptake. Conventional ascorbic acid depends on sodium-coupled transporters for entry into the cell [18,19]. The cells in different organs and tissues express different levels of these transporters, leading to highly differentiated distribution of vitamin C in different anatomical locations in the body, with the brain maintaining the highest absorption and retention of vitamin C [20].
The cell membrane of all living cells consists of specific types of phospholipids, which are a class of molecules with a water-soluble ‘head’ attached to lipid ‘tails’. The phospholipids naturally arrange themselves into bilayers, forming a barrier to protect and control the intracellular environment. The cell membrane is selectively permeable and houses several types of proteins, including the vitamin C transporter, which facilitates entry into the cell for nutrients that cannot cross the membrane [18]. Different types of phospholipids can influence membrane fluidity and therefore cellular communication [21,22,23]. Phosphatidylcholine, a type of phospholipid, is the major component of mammalian cell membranes, helps modulate inflammation [24], and plays additional roles in energy storage [25], nerve insulation [26,27], and cell communication [28]. Phosphatidylcholine has beneficial effects on cardiovascular health by helping to maintain membrane cholesterol homeostasis and prevent cholesterol over-accumulation [29]. It also supports brain health and cognition [30] through support of neuronal regeneration [31].
Liposomes are small vesicles composed of phospholipids and occur naturally as extracellular vesicles, playing key roles in communication throughout the body [32]. Liposomal delivery of encapsulated nutrients into living cells may happen in several ways [33]. The most straightforward mechanism involves the fusion of the liposomal encapsulation material with the cell membrane, leading to delivery of the encapsulated nutrients into the cell’s cytoplasm [34]. This mechanism is important in the case of liposome-encapsulated vitamin C because the beneficial phospholipids become integrated into the cell membrane. Another mechanism involves endocytosis, in which a cell swallows the liposome in a similar process as phagocytosis [35]. In that case, an intracellular degradation or digestion of the liposome results in both the encapsulated nutrient and the lipids being made available in the cell’s cytoplasm.
Liposomes can be engineered synthetically using specific health-supporting phospholipids to encapsulate nutrients that benefit from enhanced bioavailability at the cellular level. Liposome-mediated delivery of vitamin C offers an alternative method with potential advantages over the rate-limiting constraints of sodium-coupled transporters described above [35]. Liposomes have been used extensively in drug delivery for their bioavailability-enhancing properties, ease of site-specific targeting, and reduced immunogenetic capabilities [36,37]. In drug delivery, the size, lipid composition, electrical charge, and molecules incorporated on the exterior can affect the targeting and nature of a liposome-encapsulated intervention [38,39]. Nutraceutical applications, as in the context of vitamin C, typically do not utilize site-specific targeting and instead focus on enhancing the cellular uptake [34]. Liposome-encapsulated nutraceuticals have been evaluated for the enhanced bioavailability of glutathione [40], curcumin [41], and omega-3 fatty acids [42].
The objective of the clinical trial presented here was to compare the uptake and immediate downstream biological effects of liposomal vitamin C in healthy adults, using an established randomized, double-blinded placebo-controlled cross-over study design for evaluating acute effects of nutraceutical products, in which each participant served as their own control [43,44]. The phospholipid material used for liposomal encapsulation was tested to document its effects and to help evaluate its contributing effects. The study focused on changes to vitamin C levels, antioxidant capacity and protection of the blood serum, and changes to specific immune-modulating cytokines.
2. Materials and Methods
2.2. Consumable Test Products
The three active test products were provided by the manufacturer, LivOn Labs (Henderson, NV, USA). The Lypo-Spheric®/Altrient® Vitamin C product is a nutritional supplement consisting of cold-processed liposome-encapsulated vitamin C (LEC). The liposomal material without vitamin C (phospholipids) and vitamin C without the liposomal material (ascorbic acid (AA)) were provided in parallel. All three products have distinct tastes that were camouflaged by adding them into 45 mL (1.5 oz) plain rice milk immediately prior to consumption. Therefore, plain rice milk was served as the placebo.
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Enhanced Bioavailability and Immune Benefits of Liposome-Encapsulated Vitamin C: A Combination of the Effects of Ascorbic Acid and Phospholipid Membranes
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McGarry, S.V.; Cruickshank, D.; Iloba, I.; Jensen, G.S. Enhanced Bioavailability and Immune Benefits of Liposome-Encapsulated Vitamin C: A Combination of the Effects of Ascorbic Acid and Phospholipid Membranes. Nutraceuticals 2024, 4, 626-642.
https://doi.org/10.3390/nutraceuticals4040034
