Other

Adenosine 5'-triphosphate disodium (ATP) is the disodium salt form of adenosine triphosphate, the primary energy currency of cells. Oral ATP supplementation has been investigated for its potential to enhance muscular performance and physiological responses during resistance exercise. Studies indicate that a single 400 mg dose of oral ATP (as Peak ATP®) taken 30 minutes before exercise can improve performance in trained individuals, including increased repetitions and power output during lower-body resistance training (PMID 29045315, 38193939). The mechanism may involve enhanced blood flow, improved neuromuscular function, or modulation of purinergic signaling pathways. While ATP is rapidly degraded in the gastrointestinal tract, evidence suggests bioavailable forms may exert extracellular effects via purinergic receptors that influence muscle activation, fatigue resistance, and vascular tone (PMID 38193939, 29045315). However, long-term efficacy and systemic absorption remain areas of ongoing research.

Alpha-lipoic acid (ALA) is a potent endogenous antioxidant that plays a critical role in mitochondrial energy metabolism and protects against oxidative stress by regenerating other antioxidants such as vitamins C and E, and glutathione. ALA and its reduced form, dihydro lipoic acid, exhibit strong free radical scavenging properties and modulate signaling pathways involved in inflammation and endothelial dysfunction, making it relevant in conditions like diabetic peripheral neuropathy (DPN), cardiovascular disease, and obesity (PMID 22607646, 24005184). Clinical evidence supports intravenous ALA at 600 mg/day for improving neuropathic symptoms and nerve conduction velocities in DPN, with oral supplementation also showing benefits, though to a lesser extent (PMID 22837391, 15529620). ALA supplementation has been shown to significantly reduce C-reactive protein levels, indicating anti-inflammatory effects (PMID 29753588), and may promote modest weight loss, with a meta-analysis showing an average 1.27 kg greater weight reduction compared to placebo (PMID 28295905). Additionally, ALA may improve lipid profiles by reducing oxidized LDL and other atherogenic markers, suggesting a role in cardiovascular risk reduction (PMID 22607646). However, under certain conditions, ALA may act as a pro-oxidant, particularly in the presence of transition metals, highlighting the need for cautious use in individuals with metal overload (PMID 20716905).

Alpha-carotene is a dietary carotenoid found in orange and yellow vegetables such as carrots and sweet potatoes. It functions as a provitamin A carotenoid, meaning it can be converted to retinol in the body, and also exhibits antioxidant properties that may help protect cells from oxidative damage. Observational studies have associated higher plasma levels of alpha-carotene with reduced risk of chronic diseases, including cardiovascular disease and certain cancers, likely due to its role in mitigating oxidative stress (PMID 20738040, PMID 26018887). However, clinical trial evidence specifically on alpha-carotene supplementation is lacking. Most research has focused on beta-carotene, which has shown potential harm in smokers at high doses, raising caution about isolated carotenoid supplementation (PMID 20738040, PMID 12804424). Therefore, current evidence supports obtaining alpha-carotene from whole food sources rather than supplements.

Ascorbyl palmitate is a fat-soluble derivative of vitamin C (ascorbic acid) formed by esterifying ascorbic acid with palmitic acid. It functions as an antioxidant in lipid environments, protecting cell membranes and lipoproteins from oxidative damage. Unlike ascorbic acid, which is water-soluble and rapidly excreted, ascorbyl palmitate provides antioxidant activity in both aqueous and lipid phases due to its amphiphilic nature, making it particularly effective in protecting against lipid peroxidation (PMID 14871474). While direct studies on ascorbyl palmitate supplementation in humans are limited, research on vitamin C indicates that higher plasma ascorbate levels correlate with increased resistance to ex vivo lipid peroxidation in a dose-dependent manner, suggesting potential benefits of lipid-soluble vitamin C forms like ascorbyl palmitate in enhancing systemic antioxidant defenses (PMID 14871474). Its use may be beneficial in conditions involving oxidative stress, such as inflammation and viral infections, where vitamin C has been proposed to modulate immune function and reduce cytokine storm (PMID 32882216).

Astaxanthin is a potent carotenoid antioxidant derived from microalgae, known for its ability to combat oxidative stress and inflammation. Clinical evidence suggests that astaxanthin supplementation increases plasma antioxidant capacity, significantly reducing markers of lipid peroxidation such as malondialdehyde (MDA) and isoprostane (PMID 30982442, 21480416). It has demonstrated beneficial effects on metabolic health, including improved glucose metabolism, reduced systolic blood pressure, and decreased visceral fat in individuals with type 2 diabetes (PMID 29384321). Additionally, astaxanthin supplementation at 6 mg/day increased glutathione levels, a key endogenous antioxidant, in active young men (PMID 34611051). In patients with rheumatoid arthritis, 20 mg/day for 8 weeks significantly improved clinical outcomes and reduced inflammatory markers including CRP, ESR, and IL-6 (PMID 40569081). Doses ranging from 1 to 20 mg/day have been safely used in human trials without significant adverse effects (PMID 30982442, 29384321, 40569081, 31788888).

Benfotiamine is a fat-soluble thiamine (vitamin B1) derivative with enhanced bioavailability compared to water-soluble thiamine salts. It exerts its primary therapeutic effects by increasing intracellular thiamine levels, thereby supporting transketolase activity in the pentose phosphate pathway. This action helps divert glucose metabolites away from harmful pathways implicated in diabetic complications, including the formation of advanced glycation end products (AGEs), activation of protein kinase C, and increased flux through the polyol and hexosamine pathways—mechanisms strongly linked to the development of diabetic neuropathy (PMID 15733949, 20519180). Research suggests benfotiamine may improve symptoms of diabetic polyneuropathy, including pain and neurological deficits, by reducing oxidative stress and improving microvascular blood flow (PMID 20519180, 8). Emerging evidence also supports its potential role in addressing neuropathic pain when conventional therapies are ineffective (PMID 26485261).

Bifidobacterium animalis subsp. lactis B420 is a probiotic strain studied for its potential to support gut health and metabolic function. While direct studies on B420 are limited, research on closely related strains such as B. lactis HN019 and BB-12 provides insight into its potential mechanisms and benefits. These strains have demonstrated the ability to modulate gut microbiota composition, improve intestinal transit time, and support immune and metabolic health (PMID 21663486, PMID 17315077). B. lactis HN019 significantly reduced whole gut transit time at doses of 1.8 and 17.2 billion CFU/day in adults with functional GI symptoms, with greater efficacy at the higher dose (PMID 21663486). In elderly subjects, supplementation with B. lactis HN019 at doses as low as 6.5 x 10^7 CFU/day increased fecal bifidobacteria counts, indicating a dose-responsive colonization effect (PMID 17315077). Although B420 specifically has not been studied in these trials, it shares taxonomic and functional similarities with these well-characterized strains. Preclinical and in vitro studies suggest bifidobacteria can enhance gut barrier function, compete with pathogens, and influence host metabolism through short-chain fatty acid production and immune modulation (PMID 25295282). However, clinical efficacy remains strain-specific, and benefits cannot be extrapolated across different probiotics (PMID 38717051).

Bifidobacterium animalis subsp. lactis CECT8145 is a probiotic strain belonging to the B. animalis species, commonly used in functional foods and dietary supplements. While specific human clinical trials on CECT8145 are not detailed in the provided literature, related research on B. animalis strains indicates potential benefits including modulation of gut microbiota, enhancement of intestinal barrier function, and immunomodulatory effects (PMID 29128720). Probiotics like B. animalis are thought to act through mechanisms such as competitive exclusion of pathogens and interaction with host immune cells. However, B. animalis strains, including those closely related to CECT8145, show limited growth in human milk and higher susceptibility to lysozyme compared to human-derived bifidobacteria, which may influence their survival in the gastrointestinal tract (PMID 19943182). Despite this, B. animalis strains are widely consumed and considered safe, with evidence supporting their fecal recovery after oral administration, suggesting transient gut presence (PMID 23549409).

C8 MCT (caprylic acid) is a rapidly absorbed medium-chain triglyceride that is preferentially metabolized in the liver to produce ketones, providing a quick source of energy independent of carnitine transport. Research suggests C8 MCT oil supports metabolic health by enhancing ketone production, which may benefit muscle oxidative capacity under catabolic conditions such as cachexia (PMID 32801267). In preclinical models, MCT supplementation reduced mortality in low-birth-weight neonates, likely due to improved energy availability (PMID 15737432). MCTs are also used therapeutically in fatty acid oxidation disorders, where long-chain fats cannot be metabolized; in these cases, MCTs provide an alternative fuel source, with recommended intake of 10–25% of total energy (PMID 39203843). Additionally, MCTs have antimicrobial properties, with studies showing reduced gastrointestinal fungal burden in preterm infants (PMID 35631300). While most research uses total MCT oil, C8 is considered the most ketogenic form, making it a preferred choice for ketogenic diets and cognitive support.

Caffeine is a central nervous system stimulant and ergogenic aid found in coffee, tea, chocolate, and dietary supplements. It enhances athletic performance by improving endurance, high-intensity efforts, resistance exercise, and cognitive-motor function in team and combat sports, likely through adenosine receptor antagonism, increased catecholamine release, and enhanced fat oxidation (PMID 37722778, PMID 28495846). Caffeine also exhibits antioxidant properties, which may contribute to its protective effects against certain chronic diseases, though these benefits are dose- and source-dependent (PMID 36361861). Acute supplementation improves exercise performance regardless of habitual caffeine intake, indicating that tolerance does not significantly blunt its ergogenic effects (PMID 28495846). Caffeine ingestion before exercise can increase postexercise energy expenditure, particularly at higher doses (4.5 mg/kg), suggesting a role in energy metabolism (PMID 24901809). While generally safe, adverse events—including cardiovascular and neurological symptoms—have been reported, especially with high-dose or energy drink formulations (PMID 32753134).

Choline is an essential nutrient involved in numerous physiological processes, including phosphatidylcholine biosynthesis, lipoprotein metabolism, neurotransmission (as a precursor to acetylcholine), and methyl group donation for epigenetic regulation (PMID 28901218, PMID 31394787). It plays a critical role in fetal brain development, and maternal choline supplementation during pregnancy has been associated with improved infant information processing speed and cognitive outcomes, particularly when intake is tightly controlled (PMID 29217669). While most pregnant women in the U.S. do not meet the recommended intake of 450 mg/day, evidence from randomized trials on long-term child neurodevelopment remains mixed, with some studies showing no significant cognitive benefits from supplementation (PMID 27806977, PMID 29217669, PMID 40077755). Choline supplementation has also been studied in children with fetal alcohol spectrum disorders (FASD), where it may improve memory and attention deficits (PMID 27806977). Additionally, forms like alpha-glycerylphosphorylcholine (alpha-GPC) are being explored for their potential to modulate methylation biomarkers such as S-adenosylhomocysteine (SAH), which is linked to cardiovascular and neurological disease risk (PMID 40883125).

Docosahexaenoic acid (DHA) is an omega-3 fatty acid essential for brain, retinal, and cardiovascular function. It plays a critical role in neurodevelopment, particularly during fetal and infant growth, with higher maternal intake associated with improved perinatal outcomes and longer gestation (PMID 30521670, PMID 30480773). DHA also contributes to the resolution of inflammation through specialized pro-resolving mediators, and combined supplementation with EPA has been shown to increase circulating levels of these beneficial lipid mediators, especially in individuals with low dietary fish intake (PMID 38518540). While evidence for cardiovascular protection is mixed, higher doses of omega-3s (≥1 g/day) may reduce major adverse cardiovascular events, particularly in those with elevated baseline risk (PMID 32634581, PMID 32114706). DHA is well tolerated in infants and adults, with dose-dependent increases in blood levels observed across multiple studies (PMID 25997653).

Dietary fiber plays a critical role in supporting gut health and metabolic function, primarily through fermentation by gut microbiota into short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate, which are associated with anti-inflammatory and protective effects in the colon and systemic metabolism (PMID 35807739, PMID 35902900, PMID 36796439). Soluble fibers, including beta-glucan, pectin, inulin, and resistant starch, are particularly effective at modulating the gut microbiome, enhancing microbial diversity, and improving markers of metabolic health such as serum lipid profiles and energy homeostasis (PMID 35807739, PMID 34684471, PMID 36796439). Individual responses to fiber supplementation vary, with habitual fiber intake influencing microbiota responsiveness, suggesting that consistent intake may enhance efficacy (PMID 35902900). Increased fiber consumption is linked to reduced body weight, adiposity, inflammation, and improved lipid metabolism, making it a valuable component of dietary strategies for obesity and cardiovascular disease prevention (PMID 34684471, PMID 36796439).

Dihydronicotinamide mononucleotide disodium salt (NMN) is a reduced form of nicotinamide mononucleotide, a precursor to nicotinamide adenine dinucleotide (NAD+), a coenzyme critical for cellular energy metabolism, DNA repair, and sirtuin activation. While preclinical studies suggest that NMN supplementation may enhance NAD+ levels and improve metabolic and age-related physiological decline, clinical evidence in humans remains limited and inconsistent. Recent meta-analyses of randomized controlled trials show that NMN supplementation (250–2000 mg/day for up to 12 weeks) significantly increases blood NAD+ levels, but does not consistently improve markers of glucose metabolism (e.g., fasting glucose, insulin, HbA1c) or lipid profiles in middle-aged and older adults (PMID 39531138, PMID 38111854). Notably, one preclinical study in mice found that NMN supplementation blunted the beneficial effects of exercise on glucose metabolism in diet-induced obesity, raising concerns about context-specific efficacy (PMID 34121447). Overall, while NMN effectively raises NAD+ in humans, its functional health benefits remain unproven, and long-term safety and optimal dosing are not well established (PMID 37068054, PMID 36510042).

Eicosapentaenoic acid (EPA) is a long-chain omega-3 fatty acid primarily found in marine sources that plays a key role in cardiovascular and inflammatory regulation. EPA exerts cardioprotective effects through multiple mechanisms, including triglyceride reduction, anti-inflammatory actions, improved endothelial function, and stabilization of atherosclerotic plaques. Evidence from randomized controlled trials and meta-analyses indicates that EPA supplementation, particularly at higher doses (≥1 g/day), is associated with a significant reduction in major adverse cardiovascular events (MACE), especially in individuals with elevated triglycerides or established cardiovascular disease. A dose-related meta-analysis found that omega-3 supplementation providing at least 1 g/day of EPA (alone or with DHA) reduced myocardial infarction risk by 14–19% (PMID 35290840). In the VITAL trial, supplementation with 460 mg/day EPA + 380 mg/day DHA increased circulating lipid mediators of inflammation resolution, particularly in individuals with low baseline fish intake (PMID 38518540). Earlier trials also support cardiovascular benefits of marine n-3 fatty acids post-myocardial infarction, though recent studies show more modest effects in populations already receiving optimal medical therapy (PMID 20929341, 32114706).

Fructooligosaccharides (FOS) are non-digestible prebiotic fibers that selectively stimulate the growth of beneficial gut bacteria, particularly Bifidobacteria, thereby modulating the intestinal microbiota (PMID 25519697, 16107902). FOS are fermented in the colon to produce short-chain fatty acids (SCFAs), which lower luminal pH and may improve gut barrier function and reduce inflammation. These mechanisms underlie their potential role in managing gastrointestinal disorders, including inflammatory bowel disease (PMID 16107902). Some evidence suggests FOS may help regulate blood glucose by improving insulin sensitivity and reducing postprandial glycemia, particularly in animal models, though human data remain inconsistent (PMID 22460261, 21040500). FOS are commonly derived from sucrose via enzymatic synthesis or extracted from plants and are used in functional foods and supplements for their bifidogenic and metabolic effects (PMID 25519697).

Gamma-carotene is a lesser-studied carotenoid with limited direct research on its health effects. Unlike beta-carotene, which has been extensively evaluated in clinical trials, gamma-carotene lacks robust human studies on its efficacy, safety, and optimal intake. Carotenoids in general function as antioxidants and may contribute to cellular protection against oxidative stress, but evidence for gamma-carotene specifically is insufficient to establish definitive benefits. Notably, high-dose beta-carotene supplementation has been associated with increased lung cancer risk in smokers and potential increases in mortality in some populations, raising caution about generalizing benefits across all carotenoids (PMID 20738040, 22254063, 8164841333). Given the structural and functional similarities among carotenoids, these findings underscore the need for caution with high-dose supplementation, particularly in at-risk populations such as smokers.

Glutathione (GSH) is the most abundant endogenous antioxidant in the body, playing a critical role in neutralizing reactive oxygen species (ROS), maintaining cellular redox balance, and supporting immune function (PMID 24791752, 29604197). It is synthesized intracellularly from three amino acids—cysteine, glycine, and glutamate—and is particularly concentrated in the liver, lungs, and brain. GSH participates in detoxification, mitochondrial integrity, immune regulation, and post-translational modification of proteins via glutathionylation, influencing processes such as apoptosis, inflammation, and neural signaling (PMID 29604197, 27603810). Depletion of GSH is associated with oxidative stress-related conditions including liver disease, cystic fibrosis, and psychiatric disorders (PMID 27603810, 32438253). While oral GSH supplementation increases blood GSH levels in healthy adults (PMID 24791752), its bioavailability is limited by intestinal degradation; thus, precursors like N-acetylcysteine (NAC) may be more effective for boosting intracellular GSH (PMID 2603810, 37405379). Notably, in critically ill patients with COVID-19, intravenous NAC improved oxygenation, likely through enhancing GSH-dependent antioxidant defenses (PMID 37405379). However, inhaled GSH did not improve lung function in cystic fibrosis patients over 6 months (PMID 23631796), and GSH's role in cancer is complex, with evidence suggesting it supports tumor initiation but may become redundant in advanced stages (PMID 25620030).

Hyaluronic acid (HA), also known as hyaluronan or sodium hyaluronate, is a glycosaminoglycan naturally present in connective tissues, synovial fluid, skin, and cartilage. It plays a critical role in maintaining tissue hydration, viscoelasticity, and joint lubrication, and is involved in cell signaling, wound healing, and antioxidant activity (PMID 11123099, PMID 29351375). Oral supplementation with low molecular weight hyaluronic acid has shown promise in improving joint function and reducing pain in individuals with mild knee osteoarthritis, potentially by restoring synovial fluid properties and supporting cartilage integrity (PMID 33592868). Additionally, emerging evidence supports its role in skin health, where daily intake (e.g., 30 mg) in combination with collagen and vitamin C significantly improves skin density, texture, firmness, and hydration, likely due to enhanced dermal matrix support (PMID 38931263, PMID 25342893).

Hydrolyzed marine collagen peptides are bioactive proteins derived from fish collagen that are enzymatically broken down into low-molecular-weight peptides for enhanced absorption. Clinical evidence supports their role in improving skin health and joint function. Oral supplementation has been shown to significantly improve skin hydration, elasticity, and dermal density, with benefits observed as early as 6 weeks and increasing through 12 weeks of daily intake (PMID 29949889, 31990581, 23949208). These effects are attributed to the stimulation of fibroblast activity and increased synthesis of extracellular matrix components like collagen and proteoglycans. For joint health, collagen peptides demonstrate analgesic and anti-inflammatory properties, reducing pain and stiffness in individuals with osteoarthritis or activity-related joint discomfort (PMID 24852756, 30122200, 34371963). The Gly-Pro-Hyp tripeptide motif, abundant in hydrolyzed collagen, is believed to play a key role in tissue targeting and bioactivity. Benefits appear dose-dependent and more pronounced in individuals with existing joint or skin concerns.

Inositol, particularly myo-inositol, is a naturally occurring compound involved in insulin signaling, cellular metabolism, and neurotransmitter regulation. It functions as a second messenger in insulin pathways, improving insulin sensitivity, which underlies its benefits in metabolic and reproductive health. Clinical evidence supports its use in reducing the risk of gestational diabetes, especially in high-risk pregnancies, with antenatal supplementation showing significant protective effects (PMID 36790138). Inositol also improves metabolic parameters such as blood pressure, lipid profiles, and insulin resistance in individuals with metabolic syndrome (PMID 34330516, PMID 22192068, PMID 31283839). In reproductive health, myo-inositol supplementation enhances ovarian response and embryo quality in women with poor ovarian reserve undergoing assisted reproduction (PMID 32018040). Additionally, inositol may support neonatal lung maturation and reduce complications in preterm infants with respiratory distress syndrome (PMID 31283839). Overall, inositol is well-tolerated with minimal side effects across diverse populations.

Lactic Acid Bacteria (LAB) are a group of probiotic microorganisms commonly used in food and dietary supplements, primarily for their beneficial effects on gut health and immune modulation. LAB, including genera such as Lactobacillus and Bifidobacterium, help maintain intestinal microbial balance, inhibit pathogen colonization, and support the integrity of the gut barrier. Clinical evidence suggests that specific strains of LAB can improve outcomes in conditions such as Helicobacter pylori infection by enhancing eradication rates and reducing antibiotic-associated side effects, thereby improving treatment compliance (PMID 11549824). Additionally, LAB supplementation has been associated with immune modulation and improved gastrointestinal function (PMID 31295241, PMID 25569274). However, the efficacy of LAB is highly strain-specific and dependent on adequate dosing, viability, and timing of administration (PMID 23906073, PMID 33947466). Despite promising results, standardization across studies remains limited, and benefits cannot be extrapolated across different strains or conditions (PMID 31295241, PMID 26447958).

Linoleic acid (LA) is an essential omega-6 polyunsaturated fatty acid (PUFA) required for normal growth and health, playing a key role in cell membrane structure and as a precursor to signaling molecules such as prostaglandins and leukotrienes. Conjugated linoleic acid (CLA), a group of isomers of linoleic acid, has been studied for its potential anti-inflammatory, antiadipogenic, and lipid-modulating effects. In humans, CLA supplementation has shown modest effects on reducing body fat mass, particularly in overweight and obese individuals, though results are inconsistent across studies (PMID 17664057, 21990002). Some trials report a significant reduction in body fat percentage with CLA supplementation (e.g., 3–4 g/day over 6 months), but these changes are often small and of questionable clinical significance (PMID 11592727, 28488685). Additionally, while animal models show improved lipid profiles, human studies have reported mixed outcomes, including reductions in HDL cholesterol and increases in lipoprotein(a), raising concerns about cardiovascular safety (PMID 11578253). CLA does not appear to significantly affect immune function in healthy adults (PMID 11578253, 17490954). Overall, evidence supports only a minor role for CLA in body composition modification, with no established benefit for immune or cardiovascular health in humans.

Lipase is a digestive enzyme that catalyzes the hydrolysis of dietary fats into free fatty acids and monoglycerides, facilitating fat digestion and absorption in the small intestine. It is primarily produced by the pancreas and is essential in the management of exocrine pancreatic insufficiency (EPI), where lipase supplementation helps improve fat digestion and reduce steatorrhea. Microbe-derived lipase supplements have shown efficacy comparable to animal-derived pancreatic enzymes, with advantages including stability across a broader pH range and lower required dosages (PMID 24018836, PMID 19152478). Emerging research also explores lipase inhibition as a strategy for weight management, where compounds like mangiferin may reduce dietary fat absorption by inhibiting pancreatic lipase activity (PMID 30401639, PMID 40265679). However, direct evidence for lipase supplementation in non-pancreatic digestive complaints remains limited and requires further clinical validation.

Lutein is a xanthophyll carotenoid found abundantly in leafy green vegetables and egg yolks, selectively accumulated in the macula of the retina where it functions as a blue-light filter and antioxidant, contributing to macular pigment optical density (MPOD) and protecting against oxidative stress. Supplementation with lutein has been shown to increase serum lutein levels and MPOD in a dose-dependent manner, with doses ranging from 6 to 20 mg/day, and may improve visual function in individuals with early age-related macular degeneration (AMD) or chronic central serous chorioretinopathy (CSC). Clinical trials report significant improvements in best-corrected visual acuity (BCVA), contrast sensitivity, and reductions in subfoveal fluid height with lutein-containing antioxidant supplements over 6–12 months (PMID 28171877, 23312760, 23385792). Meta-analyses suggest lutein supplementation alone can significantly increase MPOD, though effects on visual acuity are more modest and variable (PMID 25358528). Even in healthy individuals, lutein supplementation (6–12 mg/day) enhances MPOD and photostress recovery (PMID 18294739, 32998324).

Lycopene is a non-provitamin A carotenoid found predominantly in tomatoes, watermelon, and grapefruit, known for its potent antioxidant properties. It has been studied for its potential role in reducing oxidative stress, supporting prostate health, and lowering blood pressure. Clinical evidence suggests that lycopene supplementation, particularly at doses above 12 mg/day, may significantly reduce systolic blood pressure in individuals with elevated baseline levels (PMID 24051501). Additionally, a pilot study in men with benign prostatic hyperplasia (BPH) showed that 15 mg/day of lycopene for 6 months inhibited disease progression, suggesting a potential role in prostate health (PMID 18156403). Lycopene also increases plasma antioxidant capacity and may reduce LDL oxidation, although results on immune function have been inconsistent (PMID 10878653, 11477460). Despite promising observational data linking high dietary lycopene intake with reduced risk of prostate cancer, clinical trial evidence remains limited and inconclusive (PMID 6, 18156403).

Modified cellulose, specifically carboxymethylcellulose (CMC), is a low-fermentability soluble fiber used as a dietary supplement for managing fecal incontinence (FI), particularly in individuals with loose or liquid stool. In a randomized clinical trial, CMC supplementation did not significantly improve FI frequency compared to placebo, and was associated with lower in vitro fermentation by colonic bacteria compared to other fibers like gum arabic and psyllium (PMID 25155992, 23556460). This low fermentability may limit the production of short-chain fatty acids and reduce beneficial effects on gut health and stool consistency. While generally well-tolerated, CMC appears less effective than more fermentable fibers for improving bowel control and colonic metabolism.

Methylsulfonylmethane (MSM) is an organosulfur compound found in some plants and available as a dietary supplement. It is commonly used for its potential anti-inflammatory and antioxidant properties, particularly in supporting joint health and reducing symptoms of osteoarthritis. MSM may also support connective tissue integrity and modulate immune responses, though human clinical evidence remains limited. Animal studies show that orally administered MSM is absorbed and distributed to tissues, including the brain and cerebrospinal fluid, where it can be detected via spectroscopy (PMID 17236113, 31111938). While no major toxicity was observed in broilers at doses up to 2,000 mg/kg body weight, human safety data are still emerging. Preliminary evidence suggests MSM may reduce oxidative stress and support exercise recovery, but more high-quality human trials are needed to confirm these benefits (PMID 31111938).

Nicotinamide mononucleotide (NMN) is a precursor to nicotinamide adenine dinucleotide (NAD+), a coenzyme critical for cellular energy metabolism, DNA repair, and regulation of aging-related pathways. NAD+ levels decline with age, and preclinical studies suggest that NMN supplementation can restore NAD+ levels, improving metabolic health, mitochondrial function, and cardiovascular parameters. In humans, NMN supplementation has been shown to significantly and dose-dependently increase blood NAD+ concentrations, with doses of 300–900 mg/day producing measurable elevations over 60 days (PMID 38430946, 36797393, 39116016). However, clinical evidence for functional benefits—such as improved glucose metabolism, lipid profiles, insulin sensitivity, or physical performance—remains limited and inconsistent across trials (PMID 39116016, 38430946, 36797393). While some studies report trends toward improved arterial stiffness or insulin sensitivity, these findings are not consistently replicated, and larger, longer-term trials are needed to confirm physiological benefits (PMID 36797393, 38430946). NMN appears safe and well-tolerated in healthy middle-aged adults at doses up to 900 mg/day for 60 days (PMID 36482258, 38430946).

Oleic acid (OA), a monounsaturated omega-9 fatty acid, is a major component of olive oil and contributes to its well-documented cardiovascular and metabolic benefits. It exerts protective effects by reducing oxidative stress, improving lipid profiles, and supporting mitochondrial function. Studies show oleic acid ameliorates adrenaline-induced mitochondrial dysfunction in rat heart tissue, preserving membrane integrity and respiratory enzyme activity, likely through direct binding to adrenaline (PMID 30580019). It also enhances fatty acid digestibility in dairy cows when replacing stearic acid in dietary fat blends, suggesting improved metabolic utilization (PMID 34127262). Additionally, oleic acid plays a structural and functional role in increasing the bioavailability of phenolic compounds like hydroxytyrosol by forming lipophilic esters such as hydroxytyrosyl oleate, which exhibit enhanced cellular uptake and anti-proliferative effects in neuroblastoma cells (PMID 36293207). Human and animal studies indicate that oleic acid, along with olive oil polyphenols, reduces serum lipids and oxidative damage, contributing to cardioprotection (PMID 18815741, 16900950). Furthermore, oleic acid stimulates cholecystokinin (CCK) release, though less potently than longer-chain fatty acids like DHA, and may contribute to satiety and reduced energy intake (PMID 22313587).

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential fatty acids with well-documented anti-inflammatory, antiarrhythmic, antithrombotic, and immunomodulatory properties (PMID 31840567). They play critical roles in cardiovascular health, mental health, and modulation of oxidative stress, with evidence suggesting benefits in heart failure, depression, and high-risk cardiovascular populations when used appropriately (PMID 33907071, 39201362, 39805484). While general omega-3 supplementation has not consistently improved cardiovascular outcomes in the general population, high-dose, purified EPA (icosapent ethyl) significantly reduces cardiovascular events in high-risk patients on statins with elevated triglycerides (PMID 33907071). Dose and formulation appear critical: higher doses of EPA and adequate tissue status may be necessary to observe clinical benefits, particularly for cardiovascular mortality and heart failure (PMID 29189735, 39805484). Omega-3s may also exert antioxidant effects in vascular tissues, counteracting oxidative stress despite their susceptibility to oxidation (PMID 24345866).

Polyglutamic acid, specifically in the form of polyglutamyl folic acid, refers to the naturally occurring form of folate found in foods, where glutamate chains are attached to the folate molecule. This polyglutamate structure must be deconjugated by intestinal enzymes (e.g., gamma-glutamyl hydrolase) to monoglutamyl forms before absorption, which limits its bioavailability compared to synthetic folic acid. Research shows that heptaglutamyl folic acid has lower bioavailability than monoglutamyl folic acid or synthetic folic acid, with significantly smaller increases in serum and erythrocyte folate concentrations after supplementation (PMID 14985217). In contrast, PolyGlycopleX (PGX), a proprietary functional fiber composed of polyglutamic acid-containing polysaccharides, functions as a highly viscous soluble fiber that slows carbohydrate absorption, reduces postprandial glucose spikes, and may support weight management and metabolic health (PMID 20924393, PMID 25622538). Doses of 2.5–5 g of PGX significantly reduce acute postprandial glycaemia when taken before meals, with optimal effects observed when consumed 15–30 minutes prior to eating (PMID 20924393). PGX is well tolerated up to 10 g/day over 21 days, with minimal gastrointestinal side effects (PMID 19196472).

The term 'proprietary blend' refers to a mixture of ingredients used in dietary supplements where the exact amounts of individual components are not disclosed on the label, often protected as trade secrets. This lack of transparency poses significant challenges for consumers and healthcare providers, as the active ingredients may be absent, present in subtherapeutic doses, or highly variable between manufacturers (PMID 11079277, 20493463). Proprietary blends are commonly found in herbal and combination supplements, which may offer synergistic benefits, such as in traditional Chinese medicine formulations or combination therapies for complex diseases like diabetes (PMID 25864650, 24074610). However, the absence of standardization and regulatory oversight increases the risk of impurities, adulterants, and potential herb-drug interactions, especially when used without medical supervision (PMID 27923318, 11843645). While some proprietary herbal formulations show promise in areas like cancer therapy or dermatology, their efficacy and safety are difficult to evaluate due to limited pharmacokinetic and pharmacodynamic data (PMID 27861268, 21114469).

Rice bran, the outer layer of the rice grain, is a rich source of dietary fiber, γ-oryzanol, tocotrienols, and bioactive peptides, which contribute to its potential metabolic and cardiovascular benefits. Clinical evidence suggests that rice bran supplementation may improve metabolic syndrome parameters, including systolic blood pressure, fasting blood glucose, and antioxidant status. A meta-analysis of 26 RCTs found significant reductions in systolic blood pressure (WMD: -3.28 mmHg) and improvements in glycemic control and lipid profiles in individuals with metabolic syndrome (PMID 41009614). Additionally, a randomized trial showed that 15 g/day of brown rice bran powder for 8 weeks improved metabolic syndrome characteristics and antioxidant enzyme activities (PMID 39775811). A specific processed rice bran containing the peptide Leu-Arg-Ala (LRA) demonstrated anti-hypertensive effects in individuals with high-normal or stage 1 hypertension (PMID 30925824). However, evidence for lipid-lowering effects remains inconclusive, with a recent meta-analysis showing no significant impact on total cholesterol, LDL-C, or triglycerides (PMID 37046340). Rice bran arabinoxylan compound (RBAC), a modified derivative, shows immunomodulatory potential with no reported hepatic or renal toxicity at doses up to 3 g/day over 6 months (PMID 37739721, PMID 31146613).

Total dietary carbohydrate is a primary energy source for the body, particularly critical during endurance exercise and for maintaining glycemic control. While the human body can synthesize glucose endogenously, dietary carbohydrates are considered conditionally essential, especially in certain metabolic disorders like glycogen storage disease type I (PMID 32102704). For athletic performance, carbohydrate ingestion during prolonged exercise (typically 30–60 g/hour) improves endurance capacity and time-trial performance, with evidence supporting both high and low glycemic index carbohydrates such as maltodextrin, trehalose, and isomaltulose (PMID 38458180). A 'food first' approach—using whole foods like bananas or sandwiches—can be as effective as commercial supplements for delivering carbohydrates during endurance activities and may reduce gastrointestinal symptoms in some individuals (PMID 35231883). In individuals with prediabetes or type 2 diabetes, specific types of carbohydrates such as inulin-type fructans (ITF) have been shown to significantly improve glycemic control in a dose-dependent manner (PMID 31805963). Total carbohydrate quantity in meals has a greater impact on blood glucose than the source or type, particularly important for people managing diabetes (PMID 15272246). Combining carbohydrates with other ergogenic aids like caffeine may further enhance physical performance (PMID 36178302).

Zeaxanthin is a dietary carotenoid that selectively accumulates in the macula of the retina, where it forms macular pigment along with lutein and meso-zeaxanthin. It functions as an antioxidant and blue light filter, protecting retinal tissues from oxidative damage and photochemical stress, which may reduce the risk of age-related macular degeneration (AMD) (PMID 23644932, PMID 18450596). Higher macular pigment levels have also been associated with improved cognitive function, particularly memory and processing speed, suggesting neuroprotective effects (PMID 29332050, PMID 34999335). Clinical trials, including the AREDS2 study, have evaluated zeaxanthin in combination with lutein and omega-3 fatty acids, showing that supplementation increases serum carotenoid levels and macular pigment optical density, with potential benefits for both eye health and cognition in older adults (PMID 18450596, PMID 29332050, PMID 34999335).