Introduction

Ethanol, widely recognized as alcohol, is a bioactive substance with a multifaceted role in modern society.1 It is consumed as an alcoholic beverage and used extensively in various industrial applications, including pharmaceuticals, cosmetics, household products, solvents, and biofuels.2 Ethanol is also present in numerous foods either as an intentional additive or a by-product of fermentation, such as in fruits, juices, breads, and sauces.3,4 Despite its ubiquitous presence, the health implications of ethanol, particularly for vulnerable groups such as children, pregnant women, and individuals recovering from alcohol dependence, necessitate a thorough examination of its exposure and regulatory guidelines.5–7 Alcohol consumption may be associated with an increased risk of preterm births, though an exact dose-response relationship has not been established.8

Ethanol can be derived from biomass fermentation, known as bioethanol, or it can be synthesized from ethylene, a petroleum-based by-product.2,9,10 Its diverse applications range from enhancing flavor and preserving food to serving as a solvent in pharmaceuticals and cosmetics.11–14 This widespread use demands comprehensive risk assessments and clear regulatory guidelines to safeguard public health.

Moderate alcohol intake was once considered heart-healthy and endorsed by the American Heart Association (AHA). However, conflicting evidence from alcohol use disorder studies and recent research indicated no cardiovascular benefit and potential harm. By 2023, the AHA updated its guidelines, indicating that even one drink per day might elevate the risk of cardiovascular disease.15 Increasing alcohol consumption is associated with heightened risks of disease and mortality.16,17

Identifying a safe level of alcohol consumption is critical but challenging. Recent studies suggest that the safest level of alcohol consumption is none, as even moderate drinking carries risks that often outweigh potential health benefits.18,19 Exposure to ethanol from multiple sources poses significant health risks, particularly when accumulated in large amounts. However, the cumulative exposure to ethanol from these various sources complicates the assessment of its overall impact on health.20–22 The study concludes that alcohol is a major global health issue, with even low levels of consumption heightening the risk of severe health issues, including cancer. This supports the UK Chief Medical Officer’s guideline that there is no safe level of alcohol consumption.18 The study suggests prioritizing public health policies that reduce alcohol consumption at the population level, such as increasing taxes, regulating prices, restricting marketing, and limiting availability. These measures are effective and cost-efficient, like those used for tobacco control. The UK is implementing these strategies, with Scotland already adopting minimum unit pricing (MUP) and similar measures planned for Northern Ireland and Wales.18 The economic impact of ethanol use is substantial. In the United States alone, alcohol-related problems cost the economy an estimated $249 billion annually, primarily due to lost productivity, healthcare expenses, and enforcement costs. Similar economic burdens are observed globally, underscoring the necessity for comprehensive public health strategies, robust regulatory policies, and effective consumer education.23–25

Ethanol’s presence in everyday products also raises cultural and religious issues. Under Islamic law, ethanol is generally considered non-halal (haram) if it acts as an intoxicant. However, ongoing debates focus on the acceptability of different types of ethanol in non-intoxicating products. Developing clear guidelines that respect religious beliefs while ensuring consumer safety is essential.12,26

A comprehensive risk assessment and well-defined regulatory guidelines regarding ethanol’s presence in everyday products are crucial. Islamic teachings emphasize the protection of mental faculties, which has led to a gradual prohibition of alcohol, culminating in a complete ban. This review underscores the necessity for a stringent regulatory framework and public health strategies to mitigate ethanol’s adverse effects while recognizing its industrial and social importance. It also examines how standards are implemented in countries with substantial Muslim populations to safeguard public health, respect cultural sensitivities, and manage economic costs effectively.

Overview of Alcohol

Ethanol, also called ethyl alcohol, is a primary alcohol derived from ethane by replacing one hydrogen atom with a hydroxyl group. Ethanol, also known as ethyl alcohol, is widely used in beverages, products, and medicines.4,27,28 Typical alcoholic beverages include beer, wine, distilled spirits, as well as combinations of these or other additives like malt liquor, fortified wine, liqueur, and cordials.29 In the food industry, ethanol’s versatility makes it valuable as a solvent, preservative, and processing agent, and it is also a byproduct of fermentation in alcoholic beverages.30 The FDA designates ethanol as a Generally Recognized as Safe (GRAS) substance for use in food products. However, ethanol must meet strict regulatory standards to ensure its safety for consumption. While moderate consumption is generally safe for most adults, excessive long-term use can lead to addiction and serious health issues.

Ethanol Production

Ethanol is a volatile compound produced through the fermentation of sugars. This process utilizes the enzyme zymase from yeast, which converts sugars into ethanol and carbon dioxide. Approximately 66% of global ethanol production is used for transportation, while 21% is allocated for industrial purposes.31

Ethanol is produced through the fermentation process, where yeast acts on carbohydrates in the absence of oxygen.32 Most ethanol is generated by fermenting sucrose-rich crops, such as sugar cane and sugar beet, or starch-rich crops, like corn and other starchy grains, using the yeast Saccharomyces cerevisiae.3 During fermentation, ethanol concentration increases up to about 15%. Beyond this level, the yeast becomes toxic, halting the fermentation process. Experimental data shows that ethanol content rises from 2.8969% after 144 hours to 3.7491% after 168 hours, demonstrating the impact of fermentation time on production.33 Ethanol concentrations below 1% (w/v) are typically achieved through natural fermentation, where sugars are converted into ethanol, which is further transformed into acetic acid, carbon dioxide, and ethyl acetate. This process maintains an acidic environment (pH ≤ 4) to prevent microbial spoilage, with ethanol levels between 0.2% and 1.0% ensuring effective preservation. When ethanol levels drop below 0.2%, acetic acid may over-oxidize, leading to an increase in pH above 4.7. Conversely, ethanol concentrations above 1% can cause the formation of ethyl acetate, which also raises the pH.11

In industrial settings, ethanol is produced not only through fermentation but also from various feedstocks such as ethylene, ethane, and glucose. While synthetic ethanol is chemically identical to fermented ethanol, achieving concentrations above 15% requires distillation. Ethanol and water form an azeotrope at 95.6%, so breaking this azeotrope and reaching higher concentrations involves using dehydrating agents or additives.34

There is growing interest in expanding the range of raw feedstocks for ethanol production to include lignocellulosic biomass and algae, in addition to traditional grain-based materials.31 Effective production of bioethanol from lignocellulosic biomass relies on pretreatment processes that enhance biomass breakdown and improve ethanol yields. Techniques such as dilute acid and alkaline sodium sulfite treatments are crucial for this purpose. For example, pretreatment of corn stover resulted in 93.0% xylose recovery, 85.0% lignin removal, and a 48.5 g/L ethanol concentration.35 However, bioethanol production faces challenges such as high enzyme costs and the presence of inhibitory compounds. Additionally, contamination by Lactobacillus spp. can produce organic acids that reduce fermentation efficiency.36

Advancements in bioconversion systems are essential for improving production efficiency and sustainability. Despite progress, achieving high saccharification rates and ethanol yields at an industrial scale remains a challenge. Future research aims to enhance enzyme performance, explore alternative feedstocks, and scale up production processes.9 Research continues to focus on developing cost-effective enzymes, optimizing biomass structures, and addressing these issues.37

Ethanol is commercially produced via fermentation or chemical synthesis. During fermentation, ethanol is created along with carbon dioxide as a by-product from the breakdown of carbon sources like starch, sugar, or cellulose by yeast or bacteria. In contrast, synthetic ethanol is derived from ethylene, a by-product of petroleum refining. In the food and beverage industry, ethanol can be present either as a result of natural fermentation or as an added processing aid.38 Bioethanol, produced from plant materials like corn stalks and wood chips, can be blended with gasoline to offer a cleaner, more resource-efficient fuel alternative to fossil fuels.39 This renewable fuel supports sustainable energy goals and helps reduce greenhouse gas emissions.

Ethanol Types

Ethanol is utilized in various forms depending on its application, with distinct types serving specific functions across different industries: Pharmaceutical-Grade Ethanol, Food Grade Ethanol, Industrial Ethanol, Denatured Ethanol, Fuel Ethanol/ Bioethanol, Technical Grade Ethanol, and Hydrated Ethanol (Table 1).

Table 1 Various Type of Alcohol

Alcohol can be produced through biomass fermentation or synthesized by hydrating ethylene, either directly or indirectly. Various catalysts, such as silica gel, montmorillonite, and bentonite, are commonly used in the indirect hydration process, particularly in industrial settings.47 However, producing synthetic ethanol can be expensive due to the significant energy required to compress ethylene and water when using phosphoric acid catalysts. In contrast, bioethanol production has become the preferred method for commercial ethanol because it is more cost-effective, relies on renewable resources like cereal grains, and avoids toxic chemicals found in petroleum-based alternatives. Many countries widely practice fermentation technology for producing fuel and potable ethanol, though the choice of feedstock varies by region.10

Ethanol and Health Disorders

When consumed, ethanol is swiftly absorbed from the stomach and small intestines into the bloodstream and then circulated to various tissues, including the brain. The rate of absorption can be influenced by factors such as body weight, food intake, and the speed of drinking. In the US, the legal blood-alcohol concentration (BAC) limit for driving is 0.08 g/dL. Alcohol absorption primarily occurs in the stomach and upper small intestine, with peak levels reached 30 to 60 minutes after consumption.32 Once in the body, ethanol is mainly metabolized in the liver, where it is converted into acetaldehyde, a compound linked to hangover symptoms. Acetaldehyde is further broken down into acetic acid and then into CO2 and H2O. Additionally, a small portion of ethanol is also excreted through urine, breath, and sweat.32 In small amounts, ethanol acts as a stimulant, but in larger quantities, it functions as a depressant, increasing the risk of various diseases. Alcohol consumption raises the risk of numerous health problems, as show in Table 2. It is a leading cause of death, particularly among young people and disadvantaged populations.19

Table 2 Alcohol and Health Problems

Acetaldehyde, a carcinogenic compound, interferes with DNA synthesis and repair, leading to stable mutations such as N2-ethyl-deoxyguanosine. Approximately 40% of Asians have a deficiency in acetaldehyde dehydrogenase, resulting in higher acetaldehyde levels and a higher risk of cancers, especially in the upper gastrointestinal tract and colon. This highlights the critical role of acetaldehyde in alcohol-related cancer development, as it can cause damage independently of ethanol.106–108 Additionally, ethanol metabolism generates oxidative stress, which contributes to various health issues, including cell damage, inflammation, liver disease, and cardiovascular problems. Reducing or avoiding alcohol is crucial to lowering the risk of cancer and other alcohol-related health disorders.84

Combining alcohol and tobacco greatly amplifies the risk of cancers in the oral cavity, pharynx, larynx, and esophagus, with the combined risk exceeding the sum of their individual risks. Alcohol is a Group 1 carcinogen associated with at least seven cancers, including bowel and breast cancer. Additionally, acetic acid, a metabolite of alcohol, can cause oxidative stress and alter arterial blood pressure.15,106

Numerous studies highlight the necessity of large-scale randomized trials to conclusively ascertain the health impacts of alcohol consumption. This ongoing debate centres around the relationship between moderate alcohol intake and health risks, particularly its potential link to diabetes [106]. Clinicians should actively screen patients for alcohol use, especially those with an elevated risk of developing diabetes, and provide targeted counselling and resources. Establishing clear alcohol consumption guidelines is crucial in mitigating excessive intake. Many healthcare settings emphasize these guidelines, with specialties such as dermatology also advocating for reduced alcohol consumption, particularly in patients with conditions like psoriasis.101,103

Ethanol and Social Disorders

Alcoholism is a neurological disorder influenced by genetic factors, childhood trauma, social environment, mental illness, and notably early alcohol consumption, which significantly increases the risk of developing the condition.23,109–111 In clinical forensic medicine, alcohol is associated with criminal behaviours such as traffic accidents, suicide, and sexual assault, as well as child abuse, partner violence, and parental abuse.32

Socially, alcohol use leads to disrupted family relationships, decreased work productivity, and increased criminal activity. Dependence often results in social isolation, with individuals prioritizing drinking over familial and social obligations. This contributes to higher absenteeism, workplace accidents, and increased healthcare costs. In conclusion, alcohol use disorder (AUD) significantly impacts families by adding burdens, disrupting social and financial stability, and causing psychological and health issues for both adults and children. Spouses often face increased emotional distress and health problems, while children may struggle with behavioural and academic difficulties. Addressing AUD effectively is crucial not only for the individual but also for the well-being of their entire family.

The NHS Digital Statistics Report indicates that approximately 900,000 hospital admissions annually are related to alcohol consumption. The NHS warns that alcohol intake during pregnancy can cause foetal alcohol spectrum disorders. Early alcohol use heightens the risk of developing heavy drinking habits and alcohol dependence in adulthood, and is linked to negative outcomes such as academic failure and violent behaviour.112

Treatment for alcohol dependence typically combines psychotherapy and pharmacotherapy, including detoxification and ongoing support such as group therapy. Medications like acamprosate, disulfiram, and naltrexone are commonly used. Despite advancements, relapse remains a challenge, underscoring the need for a comprehensive approach addressing psychological, social, and biological aspects of alcoholism.109,113 Recent studies reveal that nanozyme agar treatment in rats with alcohol poisoning decreased blood alcohol levels by 55.8% after 300 minutes, while not increasing acetaldehyde levels.114

The concurrent use of cocaine and alcohol is a dangerous combination. Cocaine increases extracellular monoamines by inhibiting dopamine (DA), norepinephrine (NE), and serotonin (5-HT) transporters (DAT, NET, and SERT). Ethanol also raises extracellular monoamines but does so through different mechanisms. Research suggests that organic cation transporter 3 (OCT3) plays a crucial role in regulating monoamine signalling in this context.115

Ethanol Contents of Daily Consumption Ethanol in Food and Drug Industry

The versatility of ethanol is proven in various applications, ranging from food processing and preservation to the use of fuel and antiseptics. Its various functions emphasize the importance of this product in various industries and everyday life (Table 3), while regulatory measures ensure the safe use of consumer products.

Table 3 Application of Ethanol in Food and Drug Industry

Industrial food products for babies and children are regulated in various countries, particularly within the EU, to limit exposure to potentially toxic chemicals. Regulations cover additives, materials in contact with food, contaminants, and hygiene standards. Data on ethanol effects in children are limited, mostly focusing on acute poisoning or research in adults and animals. Ethanol can cause acute poisoning in children at 0.3 g/kg and can be fatal at 3 g/kg. There is insufficient data on low-dose ethanol effects in children. Both the French Medicines Agency and the FDA advise against using ethanol in children’s medicines unless absolutely necessary, while the WHO recommends keeping ethanol levels below 0.5% in products for children under 6 years118Figure 1.119

Figure 1 Ethanol disposition. Physiologic factors in neonates having the potential to affect the absorption, distribution, metabolism, and excretion of ethanol when compared with adults. Red boxes show infant-specific differences compared with adult. Reproduced with permission from Marek E, Kraft WK. Ethanol Pharmacokinetics in Neonates and Infants. Curr Ther Res. 2014;76:90–97. Open Access (http://creativecommons.org/licenses/by-nc-sa/3.0/).119

Regulatory agencies like the FDA and EPA set stringent standards for residue levels to ensure the safety of food, pharmaceuticals, and other products. These standards are crucial in managing the risks associated with residual ethanol, ensuring that it remains within safe limits. To achieve this, manufacturing processes include various controls such as evaporation, purification, and rigorous quality checks. These measures help minimize the presence of residual ethanol and by-products in final products, maintaining high safety and quality standards. Consequently, while residual ethanol is a consideration, it is effectively managed through these regulatory and manufacturing practices to ensure it remains within acceptable and safe levels across different applications. Commercial products may contain ethanol added as a preservative, potentially at levels that disqualify them from halal certification.38

Alcohol Residues in Food and Drug

Ethanol is a key ingredient in various alcoholic beverages (beer, wine, spirits), fruit juices, salads, candies, burger rolls, sweet milk rolls, and fermented foods like yogurt and bread.2 Several methods for determining ethanol content in processed foods and beverages focus on liquid matrices such as soy sauce, olive oil, and alcoholic drinks. Techniques include headspace extraction with gas chromatography-flame ionization detection (GC-FID) or gas chromatography-mass spectrometry (GC-MS), and a non-GC approach using microwave dielectric analysis. A validated method combines liquid-liquid extraction with dimethyl sulfoxide (DMSO) and GC-MS to detect ethanol in kimchi, soy sauce, and gochujang. Mansur et al proposed an aqueous extraction method with magnetic stirring for analyzing ethanol in complex matrices, offering a greener alternative to DMSO-based methods. Further research is needed to assess its reliability across different food and beverage matrices.120

Ethanol in Beverages

The terms “alcohol” and “alcoholic beverage” are often confused, though they refer to different concepts. Alcoholic beverages fall into three main categories: beer, wine, and spirits, with alcohol content ranging from 3% to 50%. Beer typically has 2–6% alcohol, wine about 10–12%, and spirits over 20%.121 They are produced either by fermentation (eg, beer, wine, cider) or distillation (eg, whiskey, gin, vodka). Fermentation involves converting sugars in raw materials like grapes, grains, and fruits into ethanol, carbon dioxide, and energy through yeast action.122 Alcoholic beverages are complex mixtures of ethanol, water, sugars, organic acids, proteins, phenolics, and volatile compounds, which define their sensory characteristics. Industrially produced alcoholic beverages include beers, wines, and various distilled spirits like brandy, whiskey, and tequila. Each beverage contains major components such as ethanol and water, and minor or trace elements like fusel alcohols, organic acids, and esters. Over 1300 compounds have been identified in different alcoholic beverages.123,124

Ethanol also increases the solubility of primary flavors in beer, which can aid processes such as dealcoholizing. In addition, processing Aglianico grapes with ethanol can significantly increase sugar, acid, and anthocyanin levels, thus improving the quality and composition of the grapes, especially in less than ideal conditions.125

Co-inoculation of Hanseniaspora uvarum with Saccharomyces cerevisiae reduces ethanol production and improves grape aroma quality, producing fruitier and ester aromas. Low ethanol grapes have a more prominent fruit flavor. Although promising, further research is needed for large-scale applications.126

Research findings show that the millennial generation’s alcohol consumption behavior is influenced by functional, social, and emotional factors, with a tendency to spontaneously or planned alcohol consumption. The presence of methanol content in alcoholic beverages circulating in the market is a problem that the Government must pay attention to, and must warn the public that denatured alcohol contains methanol and is not safe for consumption.45

Ethanol in Food

Ethanol is commonly used as a food additive in various forms, serving as a solvent for flavorings and extracts, and enhancing the taste and aroma of food products. It also functions as a preservative in baked goods, extending their shelf life, and is involved in the production and as a carrier for certain food colorings. Ethanol is found in foods for several reasons, including the tolerable levels permitted in “non-alcoholic” beer and the presence of naturally occurring ethanol in bananas or fermented foods. Most food samples analyzed do not have ethanol concentrations high enough to present substantial risks from acute or chronic consumption by either adults or children.127

Although many food products contain low levels of ethanol, most do not pose a significant risk to adults or children, even with chronic consumption. For example, breads such as burger rolls and rye bread have alcohol levels between 1.18% and 1.28%, while yogurt and kefir range from 0.05% to 2%. Kombucha and must (usually made from grapes) contain 0.5% to 5% ethanol, and food additives, including extracts and flavorings, can have up to 35% alcohol content. Condiments like mustard and ketchup typically contain between 1.5% and 2% alcohol. Most critical are high chronic ethanol intakes when no labelling of ethanol exist (eg in fermented food).127

Although ethanol is present in various foods, risk assessments for low-dose exposure are limited. While small amounts generally pose minimal risk, even low doses may have toxicological implications. Chronic exposure data is insufficient to establish a safe dose, and most research focuses on higher ethanol levels from alcoholic beverages. Regulatory standards for ethanol in non-alcoholic beverages vary: in the US, drinks with ≤0.5% ethanol are considered non-alcoholic, while Canada and some Muslim-majority countries allow up to 1.1%, and the EU permits up to 1.2%. These differences reflect diverse cultural and legal views. Given the potential risks, even low ethanol levels should be minimized in foods to protect public health, as comprehensive studies on very low doses are lacking.127

Ethanol in Fruits

Ethanol levels in fresh fruits increase over time due to anaerobic sugar fermentation. For example, raw palm fruit initially has no ethanol, but levels rise to 0.6% in mature hanging fruit and 0.9%-4.5% in ripe fallen fruit. Similarly, fresh pineapple stored at 4°C for ten days saw its ethanol content increase from 0.48% to 1%. Fresh grape juice, on the other hand, had its ethanol concentration rise from 0.00029% to 2.11% after one day at room temperature, and reach 5.60% after ten days.128

Factors like low oxygen, high carbon dioxide, and storage temperature stress can increase ethanol production in fruits, causing unpleasant tastes. Key metabolic pathways involved include mitochondrial energy metabolism, glycolysis, and the Krebs cycle.129 Higher temperatures accelerate ethanol evaporation and absorption, peaking at 20°C. Ethanol mainly converts to esters in apples and grapes, and to acetaldehyde in persimmons. It affects ethylene metabolism differently: reducing ethylene in apples at 20°C but increasing it in persimmons at 2°C, with little effect on respiration rates.130

Ethanol treatment delays ripening and preserves the storage quality of papaya. It extends the lifespan of cut Bougainvillea flowers, inhibits melon ripening, and prevents grapefruit rot. Additionally, ethanol slows broccoli yellowing and fruit senescence by eliminating bacteria, fungi, and viruses.131

The halal status of naturally fermented ethanol in food is debated. The GSO standard (2538:2017) sets the maximum residue level (MRL) of ethanol in fruit juice at 0.1% (v/v). Research found ethanol and sugar levels in stored fruit juice remained constant, supporting the GSO standard.132 High ethanol levels in unfresh grape juice should be labeled non-Halal, so high-sugar fruits should be consumed fresh.128

Abundant fruit waste can be used to produce bioethanol due to its high sugar content.133 Consistent exposure to ethanol-containing fruits may have influenced the evolution of metabolic enzymes in mammals.134 Future research should explore more aspects of fruit ripening to understand its impact on fruit-eating animals.135

Long-term consumption of fruits and vegetables, particularly industrially processed ones, can lead to higher-than-expected alcohol exposure (mainly methanol and ethanol). This gradual exposure may contribute to cell and tissue damage and play a role in chronic diseases such as autism, liver diseases, cancer, diabetes, and neurological disorders, especially when combined with metabolic and genetic predispositions like folate deficiency and ADH variations.118

Ethanol in Drug

Ethanol is commonly used in oral pharmaceutical formulations as a cosolvent to enhance the solubility of poorly soluble drugs and as a preservative, with concentrations ranging from 0.6% to 76% v/v.136 Despite guidelines from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) on acceptable ethanol levels, many medications contain higher amounts.137

Ethanol, used in pharmaceuticals and cosmetics, enhances the absorption of active ingredients into the skin.138 For example, Phenobarbital Elixir BP is the sole licensed liquid phenobarbital formulation in the UK. Ethanol improves the flexibility of ethosomes for deep skin penetration and is employed in transdermal drug delivery systems, enhancing skin permeability when combined with water.139,140 It is also used in creating antibacterial and antioxidant mouthwashes by loading quercetin and mint essential oil into phospholipid vesicles.141 Studies show that ethanol can increase systemic drug exposure by enhancing gastrointestinal absorption of poorly soluble drugs, suggesting a need for further research on its effects.142

However, ethanol can affect the digestive tract by slowing gastric emptying, stimulating gastric acid secretion, and increasing intestinal permeability, which may impact drug absorption and increase exposure to lipophilic drugs.136

Although ethanol is typically present in small amounts in medications, it can still pose risks to infants and young children, as evidenced by cases of toxicity from accidental exposure. Children metabolize ethanol differently from adults, with lower levels of key metabolic enzymes, making them more susceptible to its effects. Thus, it is crucial to monitor and regulate ethanol content in medicines to ensure the safety of pediatric patients.137

Ethanol in Herbal Medicinal

Ethanol is commonly used in herbal liquid formulations and OTC medicines, often promoted for their health benefits. It acts as an extractant to produce solid, liquid, or semi-concentrated herbal or animal-based preparations, as defined by the European Pharmacopoeia 9th Edition.143 Herbal medicines are regulated by the European Pharmacopoeia and other relevant documents, which classify herbal extracts based on their physical form—liquid, semi-solid, or solid. According to the European Pharmacopoeia, extracts can be categorized into standardized extracts, measured extracts, or other types of extracts.144

Ethanol precipitation is a method used to purify traditional herbal formulas. This technique exploits the fact that most bioactive compounds are more soluble in higher concentrations of ethanol, while contaminants are less soluble. By increasing the ethanol concentration, unwanted substances precipitate out, leaving a potent bioactive concentrate that can be used to create tablets or granules.

In terms of solvent regulation, Class 3 solvents, including acetone, ethanol, and ethyl acetate, are considered to have low toxic potential and do not require health-based exposure limits like Class 1 and 2 solvents. Studies show that Class 3 solvents are typically within acceptable concentration limits and do not exceed regulatory thresholds.145

Safety concerns have emerged regarding ethanol in herbal products for children.146 Recent analyses reveal that nearly all tested products exceed WHO ethanol limits for different age groups: under 6 years (<0.5%), 6–12 years (<5%), and over 12 years (<10%). Some products even showed blood alcohol levels above toxicological limits, underscoring the need for stricter regulations on ethanol content.147

Given these concerns, experts recommend a comprehensive risk-benefit analysis to determine if the benefits of herbal products outweigh the risks associated with alcohol, especially for children. They also advise that producers in Belgium justify the use of alcohol in their products, accurately document ethanol content, and calculate alcohol intake based on recommended doses for different age groups. These measures aim to ensure safety and transparency in the use of herbal medicines containing alcohol.

Ethanol in Vinegar

Vinegar, a consumable liquid made from agricultural raw materials like starch and sugar, undergoes a double fermentation process involving alcohol and acetic acid.148,149 It consists of acetic acid, water, and a mix of alcohols, acids, aldehydes, and ketones, and contains bioactives such as polyphenols, carotenoids, phytosterols, and vitamins C and E. Vinegar, used traditionally as a seasoning and preservative, offers benefits like improved digestion and antioxidant, antidiabetic, and antimicrobial properties.149 It is produced from various sources including grapes, apple juice, honey, rice, and barley malt, with production in northeastern Asia often using cereals like rice. Key bacteria like Acetobacter aceti and yeasts such as Saccharomyces cerevisiae play crucial roles. Adding 10–25% strong vinegar to the alcohol substrate helps achieve optimal fermentation, influenced by factors such as temperature, yeast strain, and sugar and oxygen levels.150

Vinegar contains functional compounds like amino acids, sugars, vitamins, organic acids, phenolic substances, and bioactives such as lovastatin.151 Research shows black vinegar has the highest ethanol content (3.21%), while traditionally produced Nipah vinegar has the lowest (1.70%). All tested samples exceeded the Malaysian National Fatwa Committee’s ethanol limit of 1% v/v, highlighting the need for revised standards.152 Ethanol levels in vinegar, whether halal-certified or not, show no significant difference. In Islam, vinegar with ≥1% ethanol is classified as khamr and is not consumable. Saudi Arabian vinegar has 0.0228% ethanol, and brand “x” in Surabaya has 0.0117%.153 Khalas date vinegar, noted for its higher carotenoid content and antioxidant activity, demonstrates superior quality and production efficiency.154

Alcohol-Food Interaction

Consuming food before or with alcohol slows its absorption by delaying gastric emptying and boosting first-pass metabolism in the stomach and liver. A meal of about 700 kcal can reduce peak BAC and overall bioavailability by over 50%. However, such a large meal is often impractical, and current research indicates that total caloric intake is the main factor affecting alcohol absorption, rather than the type of food or macronutrients.155 Consuming alcohol with high-protein foods can slow down the absorption of alcohol, resulting in a delayed but prolonged effect. Conversely, alcohol consumed with high-carbohydrate foods can accelerate alcohol absorption, increasing blood alcohol levels more rapidly. Alcohol can also stimulate stomach acid production, which can worsen conditions like gastritis or ulcers, especially when consumed with spicy or acidic foods. Long-term alcohol consumption can lead to deficiencies in essential nutrients such as thiamine (vitamin B1), folic acid, vitamin B12, vitamin A, calcium, and zinc, potentially causing anemia, nerve damage, and immune system dysfunction.156–158

Fermented foods like kimchi, sauerkraut, and certain cheeses contain tyramine. When consumed with alcohol, particularly red wine and beer, these can cause increased blood pressure and headaches in individuals sensitive to tyramine159,160 Additionally, some herbal supplements, such as kava, valerian, and St. John’s Wort, can interact with alcohol, enhancing sedative effects and increasing the risk of dizziness and confusion.161,162 Combining alcohol with caffeine-containing beverages like coffee or energy drinks can mask alcohol’s depressant effects, leading to increased alcohol consumption and a higher risk of alcohol poisoning and alcohol-related accidents.

Food-drug interactions are increasingly important in healthcare. According to the FDA, these interactions occur when food or drinks alter a drug’s pharmacokinetics or pharmacodynamics, leading to unexpected effects. Such interactions can modify drug absorption, distribution, metabolism, and excretion, potentially causing adverse effects or new drug responses. Alcohol often interacts with various foods, altering their biological impact and raising harm risks. For instance, alcohol can reduce the effectiveness of anticoagulant medications when consumed with vitamin K-rich foods like broccoli and spinach, increasing stroke or heart attack risks. Additionally, pairing alcohol with foods such as ripe cheese or red grapes can cause hypertension in those using monoamine oxidase inhibitors (MAOIs).112

Alcohol also affects insulin or oral diabetes medications by prolonging their effect, which can result in low blood sugar.163 Chronic alcohol consumption depletes hepatic glutathione, which helps neutralize N-acetyl- p -benzoquinonimine (NAPQI). Chronic alcohol use can induce cytochrome P450 enzymes in the liver, specifically, Cytochrome P450 2E1 (CYP2E1), facilitating an increased conversion of acetaminophen to NAPQI. Alcohol can contribute to a heightened inflammatory response in the liver. Acetaminophen-induced liver injury triggers an inflammatory cascade, and alcohol can exacerbate this process. Chronic alcohol consumption impairs the regenerative capacity of the liver, leading to delayed recovery and potentially more severe liver injury.164 Additionally, taking antihistamines, such as Benadryl, with alcohol can increase drowsiness, making activities like driving dangerous.165,166

Consuming alcohol with dietary fat can exacerbate lipid peroxidation and elevate the production of reactive oxygen species. This can activate procarcinogens via cytochrome P4502E1 induction, resulting in DNA damage from oxidative stress.167,168

Halal Status of Ethanol

The global halal market is experiencing significant growth, driven by the increasing Muslim population, which is influencing various industries, including food, beverages, medicines, and cosmetics.169,170 In response to this growth, since 1997, The FAO/WHO has set general guidelines for using the term “halal”, outlining its scope, definition, criteria, and labelling requirements. These guidelines ensure that halal products comply with Islamic law, meaning they must be free from alcohol, intoxicating substances, harmful substances, and any additives derived from such substances.120,171

Religions and customs strongly influence food habits, often through dietary laws that reflect a community’s heritage and socio-cultural identity. In Islam, halal refers to foods that are clean, safe, and permissible under Islamic law, while haram means forbidden. These dietary rules are essential expressions of religious and cultural values.171 According to halal regulations and standards, there are some permissible (non-khamr) ethanol that can be present in food and beverage products.120

In Islamic teachings, the Qur’an refers to alcoholic beverages as “Khamr”, mentioned six times, and describes them as solutions produced through the anaerobic fermentation of fruits or natural sugars. The main component of Khamr is ethanol, which is responsible for its intoxicating effects, including relaxation, euphoria, and impaired judgment. Building on these religious foundations, recent fatwas have introduced new considerations regarding ethanol in halal products. According to these rulings, the ethanol content in food products is not limited as long as it is not medically harmful. In contrast, ethanol in beverages is tolerated at levels below 0.5%, provided it is also not harmful. Additionally, ethanol in intermediate products like flavourings is not restricted, as long as its presence in the final product adheres to these guidelines.11

Permissible ethanol levels in halal products differ by country: the Islamic Food and Nutrition Council of America (IFANCA) sets a limit of under 0.1%, the Korea Muslim Federation (KMF) and Malaysia’s JAKIM allow up to 0.5%, while Indonesia’s Ulema Council (MUI) permits up to 1.0%. These variations highlight the diverse interpretations of Islamic law across different regions.38

Ethanol’s halal status is determined by its source, concentration, and intended use. Ethanol concentrations below 1% are typically considered mubah (permissible) as they do not induce intoxication and are frequently used as food preservatives. For instance, vinegar containing up to 1% ethanol is deemed halal if not intended for intoxication. The MUI Fatwa No. 10 (2018) allows ethanol use in beverages up to 0.5% vol/vol, extending this allowance to low ethanol concentrations in food products that are not medically harmful.11

Ethanol derived from khamr (alcohol from grape fermentation) is prohibited due to its impurity, while ethanol from non-alcoholic sources, such as the natural fermentation of fruits, is permissible under specific conditions, especially at non-intoxicating concentrations in food and beverages. Industrial uses of ethanol, such as disinfection or as a raw material, are allowed even at concentrations above 15%, though such ethanol is considered toxic and unsuitable for consumption. Ethanol diluted from absolute or denatured ethanol is similarly restricted to industrial applications.152

In halal-certified products like spices and flavorings, ethanol is permissible if its final concentration does not exceed 0.1%. Ensuring compliance with halal guidelines, particularly concerning the ethanol source, is crucial for manufacturers targeting Muslim consumers. However, variations in halal standards across countries can complicate international compliance. Ongoing efforts to harmonize these standards aim to facilitate global trade in halal products while maintaining adherence to Islamic dietary laws.

A case study examined the application of halal standards in slaughterhouses by comparing four different certifications—GSO 993:2015, OIC/SMIIC 1:2019, HAS 23103:2012, and MS 1500:2019—across various regions. Achieving a consistent regulatory framework with unified certification and accreditation procedures necessitates close collaboration among the authorities issuing halal certifications, especially in a globalized market. (Table 4).171

Table 4 Halal Policies Related to Alcohol in Various Products Across Several Countries

Table 5 Alcohol Descriptors Guidance

Perspective

Ethanol is commonly found in foods, but data on the health risks associated with low doses are limited. Although moderate alcohol consumption may have potential benefits, such as lowering the risk of diabetes and ischemic heart disease, these effects are not fully understood and may be attributed to non-ethanol components like polyphenols. While chronic alcoholism does not affect inflammatory bowel disease (IBD) risk, long-term abuse and binge drinking are associated with immunosuppression and increased infection risk. This raises concerns about the overall benefits of alcohol, leading some experts to recommend abstinence as the safest approach.172

The debate over low-dose ethanol consumption highlights both potential benefits and safety concerns. Research in animal models suggests that low-dose ethanol may improve liver function, reduce serum urate levels, and prevent obesity.173 Specifically, 1% ethanol may help prevent colon tumorigenesis, supporting the J-curve hypothesis that low-dose alcohol could have health benefits by modulating gut bacteria and inflammatory markers.174 However, ethanol exposure leads to chronic oxidative stress and immune dysfunction in the lungs, decreasing glutathione levels and impairing immune responses. In neonates, maternal alcohol use increases the risk of sepsis and respiratory infections. Studies show that treating ethanol-exposed neonatal mice with liposomal glutathione (LGSH) can reduce oxidative stress, restore immune function, and decrease infections and lung damage, indicating LGSH as a potential therapy for prenatal alcohol exposure effects.175

Animal studies suggest that low doses of ethanol may provide some health benefits, such as improved liver function and prevention of obesity. However, the application of these findings to humans should be approached with caution because the health effects of alcohol are complex and vary based on individual factors such as genetics and lifestyle. Ethanol is converted to acetaldehyde, a carcinogen that can harm DNA and elevate cancer risk, particularly in the upper gastrointestinal tract. Although light to moderate alcohol consumption might offer some benefits, the risks posed by acetaldehyde warrant caution. Our findings suggest that light to moderate drinking does not show significant benefits on the risk of hypertension and may even be harmful when compared with abstinence or high alcohol consumption.52,53

Although extensive evidence links excessive alcohol consumption to adverse cardiovascular changes and potential cardiomyopathy, key details remain unclear. Specifically, we lack precise information on who is at risk, the timing of onset, and the exact amount and duration of alcohol exposure needed to induce disease. Addressing these questions is crucial for identifying at-risk individuals, customizing treatments, preventing misdiagnoses, and curbing disease progression.116

While excessive alcohol is known to contribute to cardiovascular remodelling and cardiomyopathy, the precise amount and duration of exposure required to trigger these conditions remain unclear. This knowledge is vital for identifying at-risk individuals, customizing treatments, and preventing disease. Although reducing alcohol intake can benefit cardiovascular patients, there is no universally safe level of consumption, and those with arrhythmias should avoid alcohol altogether.56,57 Evidence on alcohol’s impact on various arrhythmias is mixed, emphasizing the need for moderation and further research to determine safe consumption levels and individual risk factors. Abstaining from alcohol can help restore health in affected patients.61

The conversion of ethanol to acetaldehyde, a known carcinogen, further complicates the safety of ethanol in foods. Synthetic alcohols and naturally fermented alcohols differ significantly in their production processes and properties. Synthetic alcohols are produced through chemical reactions with raw materials like ethylene, resulting in highly pure products with controlled quality. Conversely, naturally fermented alcohols are derived from the fermentation of sugars by microorganisms, yielding alcohol with organic byproducts. While synthetic alcohols are widely used in industry due to their purity, naturally fermented alcohols are considered more natural and can be acceptable in a halal context if they meet halal standards. Both types of alcohol must comply with halal regulations to adhere to halal principles.

Comprehensive guidelines are needed to address the composition, measurement, production, and regulation of alcoholic beverages across different regions. These guidelines should tackle the variability in alcohol content, challenges in measurement standards, and the importance of clear labelling and consumer information. Additionally, public health risks associated with potential methanol contamination in ethanol or isopropyl alcohol underscore the need for vigilance. Consequently, the halal food community must verify the levels of natural ethanol in products like soft drinks and fruits and ensure that halal product labels accurately reflect alcohol content.128

A study has highlighted the hepatoprotective benefits of a mixture containing fermented Schizandrae Fructus pulp and Hoveniae Semen cum Fructus (MSH) against liver damage caused by ethanol. MSH has been shown to improve hepatic steatosis, inflammation, and oxidative stress by modulating lipid metabolism, reducing inflammatory cytokines, and enhancing antioxidant defenses. These results imply that MSH may offer a valuable approach for both preventing and managing alcoholic liver disease.117

The growing demand for halal products is prompting manufacturers to adhere to varying halal standards for competitive advantage. However, the lack of a universally recognized certification due to differing requirements from various certifying bodies complicates matters. Establishing a unified global halal standard and a consistent monitoring system would streamline trade and build greater confidence among producers and consumers.

Despite efforts to harmonize existing standards, unification remains elusive. It is important to include alcohol information as in Table 5, to provide consumers with the flexibility to make purchasing decisions. Collaboration between certification authorities across countries is essential to building a consistent regulatory framework, which is increasingly needed in the global marketplace.

Conclusion

Ethanol is a widely used bioactive compound found in a variety of foods, pharmaceuticals, cosmetics, and industrial products. Despite its widespread use, there is no safe level of alcohol consumption, as defined by the World Health Organization. Studies have linked small levels of ethanol to several health risks, including chronic disease, neurotoxicity, and potential carcinogenic effects, which are exacerbated by its often-unacknowledged presence in many products. These health risks have a significant impact on vulnerable populations and contribute to a large economic burden through lost productivity and health care costs. Therefore, there is a critical need for comprehensive public health strategies and stringent regulatory measures to manage the presence of ethanol in consumer products, particularly from countries with significant Muslim populations, to safeguard public health, respect cultural practices, and effectively address economic impacts. In this review we have clear Ethanol’s halal status is determined by its source, concentration, and intended use. Further research is needed to develop improved detection methods, study health impacts of trace ethanol exposure, establish standardized labelling requirements, and find alternative preservation techniques while examining economic impacts of regulations and cultural needs for ethanol-free alternatives.

Data Sharing Statement

No data was used for the research described in the article.

Ethics Approval and Consent to Participate

This research did not involve human participants, human data, or human tissue. As such, ethical approval and consent to participate were not applicable.

Disclosure

The author declares no conflicts of interest.

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