Cataracts, the loss of lens transparency, lead to symptoms like vision impairment, diminished contrast sensitivity, altered color perception, and glare (1–3). The World Health Organization reports nearly 180 million individuals globally have visual impairments, with cataracts being a significant contributor, affecting an estimated 46% of these individuals (4). Despite being largely treatable, cataracts persist as a major cause of vision loss worldwide, posing significant public health challenges across all nations (5, 6). Factors such as aging, smoking, diabetes, and ultraviolet exposure are linked to the development of age-related cataracts (7). While cataract surgery offers marked vision improvement, it is costly, with a noted shortage of surgeons in some regions (8). Addressing modifiable risks, particularly through dietary adjustments emphasizing vitamin intake, could mitigate cataracts’ health and economic impacts, as vitamins play a key role in countering oxidative stress, a fundamental trigger in cataract formation (9–11).

Vitamin E, recognized for its antioxidant properties within the ocular lens, is hypothesized to mitigate age-related cataract (ARC) development by attenuating lipid peroxidation and fortifying cellular membrane stability (12, 13). Although various epidemiological studies suggest an inverse association between vitamin E consumption and ARC incidence (14–17), this hypothesis remains contentious, with subsequent research failing to establish a consistent link (18–20).

Vitamin B6, essential for an array of metabolic, physiological, and developmental functions, functions as a critical cofactor due to its solubility in water and reactivity post-phosphorylation. Its antioxidant prowess, akin to that of carotenoids and tocopherols, plays a vital role in neutralizing oxidative stress. Notably, empirical studies have associated higher intakes of vitamin B6, along with folate and B12, with a lower prevalence of cataracts (21–25), though these findings necessitate further validation via randomized clinical trials.

Niacin, a key agent in lipid regulation, has demonstrated beneficial effects on apolipoprotein B-containing and apo A-I-containing lipoproteins, correlating with decreased nuclear cataract incidence in initial studies (26).

Given the small sample sizes in preceding research, this investigation employs data from the National Health and Nutrition Examination Survey 2005-2008 to explore more comprehensively the relationships between intake of vitamin E, B6, niacin, and cataract formation, seeking to substantiate these vitamin’ preventative roles in cataractogenesis.

The 2019 World Health Organization’s World Report on Vision confirms that over a billion people worldwide suffer from vision impairments that are preventable or treatable to avoid blindness. Additionally, the number of people experiencing partial or severe blindness is increasing at an alarming rate. Cataracts and refractive errors account for half of the cases of blindness or severe vision impairment. Although surgical treatments exist for cataracts, many eye diseases leading to blindness, including age-related macular degeneration (AMD), remain incurable. This highlights the importance of researching the mechanisms behind these diseases and slowing their progression through preventive measures. Diet and lifestyle are two of the most critically studied factors, yet they remain poorly understood by patients. These factors seem to significantly influence both the onset and progression rate of these diseases (37).

In this study, we utilized the NHANES database to investigate the potential association between the intake of vitamin E, B6, and niacin and the occurrence of cataracts.

Our findings indicate no significant correlation between the normal or low intake levels of vitamin B6 and niacin and cataract development. However, a significant association was observed with high intakes of these vitamin. Conversely, a regular intake of vitamin E showed a notable correlation with the incidence of cataracts.

In 1922, Evans and Bishop (38) unveiled Vitamin E, which encompasses diverse fat-soluble compounds (38). This category includes alpha, beta, gamma, and delta types of both tocopherol and tocotrienol, originating from plants via homogentisic acid synthesis. Serum, red blood cells, and various ocular tissues mainly contain the alpha and gamma-tocopherol forms, with alpha-tocopherol being predominant. In comparison, beta and delta tocopherols are less present in plasma (39, 40). Noteworthy is alpha-tocopherol’s significant presence in mitochondria and endoplasmic reticulum membranes, areas known for intense free-radical activity (40). Vitamin E is essential in mitigating oxidative stress, protecting cell membranes, influencing platelet aggregation, and stimulating protein kinase C (40). The ocular lens, composed of 63% water and 35% proteins (41), can turn opaque and lead to cataracts under various stress conditions, underscoring these vitamins’ importance in eye health. Various factors, including alterations in water content, abnormal protein clustering, and exposure to detrimental elements like UV and X-ray radiation, steroids, certain chemicals, or drugs, and the effects of systemic or local ailments such as diabetes, smoking, and poor nutrition, can induce lens opacity, heightening cataract risks. Such risks increase with age and are more prevalent in women than men (42). Lens damage is often exacerbated by xenobiotics that induce free radicals, leading to detrimental effects like membrane lipid peroxidation, protein inactivation, and aggregation, eventually causing lens opacification. Such free radicals particularly target the polyunsaturated fatty acids within the lens, catalyzing cataract formation. Vitamin E is known to counteract lipid peroxidation, thus aiding in the preservation of membrane integrity and functionality (43). Research has demonstrated that vitamin E can mitigate the development of cataracts induced by substances such as galactose and aminothiazole in rabbits and protect against the photooxidation of lens lipids (44). Moreover, similar to vitamin C, vitamin E has shown potential efficacy against age-related and irradiation-induced cataracts (45–47), with some studies proposing its clinical application for cataract prevention (48). Its role as a free radical scavenger, attributed to its lipid solubility and antioxidant characteristics, is believed to be pivotal in maintaining membrane health. For instance, a study by Trevithick et al. illustrated how rat lenses incubated in a solution with high glucose and serum levels exhibited increased opacity and globular degeneration over time, which was mitigated by the presence of vitamin E, highlighting its protective effects on cellular structures. In the studied lenses, the concentrations of glucose, sorbitol, and fructose exceeded those in the controls. When vitamin E at a concentration of 2.4 μm was introduced, lens swelling subsided, and normal volume was restored more quickly, despite uniform osmolarity across all external media (49). Vitamin E demonstrated a protective effect on cell membranes by influencing their permeability and osmotic balance. Ohta et al. (50) observed that cataracts developed in lenses from male Wistar rats following incubation with methylprednisolone (1.5 mg/ml). The addition of vitamin E to the incubation medium inhibited further progression of cataracts, reduced increases in lipid peroxide levels and the Na⁺/K⁺ ratio, and ameliorated decreases in reduced glutathione, glyceraldehyde-3-phosphate dehydrogenase, and Na⁺/K⁺-ATPase activities (50). Vitamin E thereby mitigated steroid-induced cataractogenesis by safeguarding the lenses from oxidative harm and functional decline of their membranes. However, extensive experimental studies and randomized clinical trials have consistently indicated that vitamin E does not confer cataract protection in humans (51, 52).

Research emphasizing the ineffectiveness of vitamin E against human cataracts, even when administered at 400 IU three times weekly (53) or daily (52), underscores the challenge of identifying an optimal dosage. This concern extends beyond just the total vitamin E intake to the specific amounts of its components.

Therefore, advancing research into the different vitamin E variants is crucial to ascertain their potential benefits, understand the optimal dosages for each, and explore their prospective roles in cataract prevention and broader clinical applications as a significant and powerful antioxidant (10). Moreover, studies have shown that vitamins and antioxidants like vitamin C, vitamin E, and carotenoids may influence the pathogenesis of diabetic retinopathy (DR) by reducing retinal neovascularization, restoring blood flow, and protecting against free radicals (54). Additionally, vitamins C and E seem to inhibit the production of vascular endothelial growth factor (VEGF) in animal models and decrease the accumulation of advanced glycation end products (AGEs). Thus, the antioxidant effects of vitamin E are critically important and widely recognized in the development and progression of certain ocular diseases.

Vitamin B6, known for its broad involvement in metabolic, physiological, and developmental functions, stands out due to its water solubility and reactivity upon phosphorylation, making it an essential cofactor in numerous biochemical reactions. It is also recognized for its potent antioxidant capacity, comparable to that of carotenoids and tocopherols, effectively neutralizing reactive oxygen species (55). Vitamin B6 exists in multiple forms, with pyridoxal 5′-phosphate (P5P) being the safest and most effective natural active form for reducing homocysteine levels. Elevated homocysteine levels disrupt autophagy, leading to abnormal crystallin protein expression, a key factor in cataract development (56). We hypothesize that vitamin B6 may reduce cataract risk by eliminating homocysteine, thus providing a potential protective mechanism. Studies have demonstrated that vitamin B6 can mitigate protein oxidation and cloudiness in cataract models treated with mercury, suggesting its potential role in delaying or even preventing cataract progression, particularly in diabetic individuals (57). The antioxidant action of vitamin B6, specifically its ability to scavenge oxygen free radicals in the lens, was significant in our findings, where high doses (Q4) correlated with a reduced incidence of cataracts, warranting further investigation into optimal dosages.

Niacin, or vitamin B3, plays a crucial role in converting to nicotinamide adenine nucleotide, crucial for energy extraction from nutrients and maintaining genetic stability. It can be synthesized from dietary tryptophan at a ratio of 60 mg to 1 mg of niacin (58). A case report has observed the occurrence of cataracts in patients with pellagra, enhancing our understanding of the relationship between Vitamin B3 deficiency and cataract development. Vitamin B3 is crucial for the synthesis of glutathione in the lens, where glutathione acts as a primary antioxidant against oxidative damage. In this particular case, the patient also had beta-thalassemia, a condition that increases iron load and oxidative stress, accelerating cataract formation (59). This finding emphasizes the importance of maintaining adequate Vitamin B3 levels to prevent oxidative stress-induced ocular diseases. Additionally, for individuals predisposed to genetic conditions, proper nutrition and antioxidant defense are vital for maintaining eye health. While high doses of niacin have been linked to lowered serum cholesterol and triglycerides and a decreased risk of myocardial infarction, they may also elevate the likelihood of cardiac arrhythmias. Our study noted a significant association between high niacin intake (Q4) and reduced cataract incidence, highlighting the necessity for further research to delineate the appropriate dosage, considering potential adverse effects.

This study’s strengths lie in its focus on the intake of vitamin E, B6, and niacin and their relation to cataract occurrence, supported by a considerable sample size. However, there are limitations: A significant limitation of our study is the reliance on participants’ self-reported history of eye surgeries to determine the presence of cataracts. While this approach offers a practical method for collecting data across large populations, it inherently carries accuracy risks. Using self-reported history of ophthalmic surgery as an indicator for cataract presence might be a potential limitation, as self-reported data can be less accurate than clinical diagnoses. This issue could impact the reliability of the observed association between vitamin intake and cataract occurrence, as the data may not accurately reflect the true incidence of clinically significant cataracts. To address this limitation in future studies, more objective diagnostic criteria or verification through medical records may be necessary to enhance the accuracy of cataract identification. Additionally, NHANES ophthalmic data does not specify the type of cataracts or provide detailed correlations between vitamin intake and various forms of cataracts. Moreover, relying on self-reported dietary information may introduce inaccuracies, and the NHANES database does not explicitly indicate whether participants are using nutritional supplements or medications that could affect vitamin metabolism. This limitation may impact our understanding of the relationship between vitamin intake and cataract occurrence. Finally, the inherent bias of cross-sectional studies precludes establishing causality.

Although this study shows a correlation between a high intake of vitamins E, B6, and niacin and a reduced risk of cataracts, caution is warranted when applying these findings to clinical practice and daily life. Firstly, the results of this study are based on cross-sectional data, which cannot be used to infer causality directly. Furthermore, while the statistical analysis shows a significant negative correlation, this does not imply that increasing the intake of these vitamins can be directly employed for the prevention or treatment of cataracts. In fact, excessive intake of certain vitamins may present potential health risks.

Before applying these research findings, further studies are necessary to validate these relationships and explore the optimal dosages and supplementation methods for these vitamins. For instance, future research could involve designing randomized controlled trials to test the effects of specific vitamin doses on cataract development and to investigate the potential impacts of long-term supplementation on eye health.

Vitamin E, combined with high doses of vitamin B6 and niacin, shows promise in potentially delaying or preventing cataract development. Such findings introduce a novel dietary approach for the clinical prevention and management of cataracts, suggesting that targeted nutrient supplementation could play a key role in maintaining ocular health and mitigating the risk of cataract formation. This insight paves the way for further research to confirm these relationships and to determine the optimal dosages for therapeutic efficacy while ensuring safety and minimizing adverse effects.

The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

G-BZ: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Writing – original draft, Writing – review and editing. XL: Data curation, Methodology, Project administration, Validation, Writing – review and editing. S-NW: Data curation, Investigation, Methodology, Software, Writing – review and editing. S-QZ: Conceptualization, Investigation, Supervision, Writing – review and editing. Z-JZ: Formal analysis, Methodology, Validation, Writing – review and editing. ND: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – review and editing.