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As is true with other colorful plant foods, grapes and grape products (i.e., skin, seed extract, wine) possess numerous health properties that are beneficial to humans. This is because they are a rich source of vitamins, minerals, and bioactive polyphenols. Grape polyphenols have been associated with an improvement in risk factors for cardiovascular disease, metabolic diseases, neurodegenerative diseases, and certain cancers, making them of great interest as functional foods.

The use of grapes for health dates to the Neolithic Period (6,000-5,800 BC). Ancient Greeks also considered grapes and wine a source of healing. Viniculture, or grapevine cultivation for wine, has become a major agricultural practice, with nearly 10,000 cultivars of Eurasian grapes and grape products around the globe, primarily in China, India, Turkey, and Europe. Modern grapes are the result of centuries of crossbreeding and selection. These varieties account for common wines, including Chardonnay, Tempranillo, and Cabernet Sauvignon.

While the health benefits of grapes are not new knowledge, the insights gained from current research have helped expand what is known about grapes and how their polyphenols contribute to circadian rhythms and disease prevention. As disease prevalence expands, so does the demand for healthful, whole-food solutions that contribute to balance.

Grapes, Grape Polyphenols, and Bioavailability

Polyphenols and phenolic compounds have the physiologic role of attracting pollinators, providing structure, protecting against sun damage, and defending plants against harmful invaders (e.g., pests, microbes, herbivores). As such, when plants are under stress, they produce greater concentrations of phenolic compounds to combat environmental damage. In animals that consume plants, this process of xenohormesis, or the process of chemical signaling from plants that can help animals adapt to changing environments, may explain some of the health benefits experienced when consuming polyphenols.

Grapes are high in polyphenols. However, different grape varieties (i.e., red versus green) have different polyphenolic content. For example, total phenolic content is greater in Concord and purple grapes versus red and green grapes. Additionally, polyphenolic content is affected by grape products (i.e., skin, seed extracts, whole grapes, wine), grape genotype, cultivation practices, soil health, and climate. There is much heterogeneity between grape varieties, but the primary phenolic compounds of interest in grapes are stilbenes (e.g., resveratrol) and flavonoids (e.g., quercetin, anthocyanins). They also contain carotenoids (e.g., lutein, beta-carotene, zeaxanthin).

For health benefits to be utilized by the body, polyphenols must be altered through the digestive process. Bioaccessibility refers to polyphenols becoming available during digestion by enzymes. Bioavailability is the amount of absorption of polyphenols by the gut and the transport of polyphenols throughout the body. Typically, only 5-10% of phenolics are absorbed in the small intestine, whereas 90-95% are absorbed in the colon. In the small intestine, phenolics undergo conjugation via glucuronidation, sulfation, and methylation or are absorbed by the intestinal cells (enterocytes). In the colon, gut microbiota metabolizes compounds via dihydroxylation, demethylation, and deglycosylation, or colonocytes absorb them. Eventually, metabolites enter the circulatory system to reach organs and tissues. These processes are affected by internal (e.g., sex, age, dose, duration of treatment, health status) and external (e.g., environmental changes) cues. The complexity of polyphenol transformation may also explain why there is much heterogeneity in individual responses to supplementation.

Total phenolic content of grapes and grape products in gallic acid equivalent (GAE):

• Green grape (peels): 037 (+/- 0.099) – 8.833 (+/- 0.239) mg/g fresh weight
• Red grape (peels): 619 (+/- 0.257) – 13.169 (+/- 0.723) mg/g fresh weight
• White grape juice: 254-389 mg/L
• Red grape juice: 1407-2246 mg/L
• Organic red grape juice: 33 +/- 50.08 mg/L
• Non-alcoholic fermented grape juice: 2128 +/- 188.09 mg/L
• Red wine (petite Sirah): 3630 mg/L
• Red wine varieties: 87-4,929.57 mg/L
• White wine varieties: 56-1,387.31 mg/L

The Circadian Rhythm and Chrononutrition

Other blogs have detailed more on circadian rhythm and chrononutrition. However, for the purposes of understanding the connection of grape polyphenols to these concepts, it’s important to acknowledge that the body is controlled by diurnal oscillations. In other words, it is programmed to automatically regulate certain processes (e.g., digestion, metabolism, sleep) at specific times of the day. However, external and environmental factors can also affect the circadian rhythm. For example, light/dark exposure, seasonal patterns, and lifestyle shifts (eating habits and patterns, social jet lag, work schedule) also affect the body’s processes and may disrupt the regular cycle. This desynchrony is associated with increased inflammation, blood pressure, calorie consumption, reduced glucose regulation, energy expenditure, and insulin sensitivity.

Coordinating food intake with the circadian rhythm (i.e., chrononutrition) is an emerging practical strategy for health. Because digestion and metabolism are regulated by the circadian rhythm, diet, meal timing, supplements, and medications are important bidirectional interactions to consider.

Grape Polyphenols and the Circadian Rhythm

Grapes have been found to influence the circadian rhythm in many ways. For example, obese animals with circadian desynchrony were given grapeseed procyanidin extract (GSPE), which restored circadian activity. Researchers also found that GSPE improved hepatic clock gene (e.g., Bmal1, Per2, Cry1, Ror-a) expression and the hepatic circadian rhythm.

However, because polyphenols act on circadian rhythms, they may need to be consumed at specific times of day. The above study found that hepatic effects were stronger when GSPE was administered in the evenings. In contrast, the diet-impaired mitochondrial activity was restored when GSPE was consumed during the day. Another study showed that grapes consumed in the morning have a greater protective effect against oxidative stress, likely due to the immune system’s circadian rhythm peaking in waking hours. Both studies suggest a time-dependent effect. Many physiological processes operate on an oscillating rhythm, so it makes sense that polyphenol consumption timing may need to be adjusted for specific times of day throughout the year.

Some animal studies suggest light exposure may translate into how the body receives nutrition from food. A rat study suggests that consuming grapes in a shorter light period (i.e., winter) led to greater bioavailability of grape polyphenols. Researchers also found that the intake of organically grown grapes (versus conventionally grown grapes) results in greater metabolites of polyphenols in the blood. Another rat study showed that grape consumption influenced energy homeostasis and leptin signaling depending on the photoperiod (short-day vs. long-day). Fruit consumption in short-daylight photoperiods (i.e., winter) increased leptin sensitivity, thereby affecting energy homeostasis. These studies suggest that when polyphenols are consumed (seasonally or under certain light conditions) may be just as important as what is consumed, potentially influencing both metabolism and circadian regulation.

The timing of grape polyphenol consumption within a 24-hour period may also influence its effects in humans. In a clinical trial with 32 healthy adults, participants consumed a grape drink (equivalent to 1.5 servings of grapes) alongside a high-fat meal in the morning and evening. Urine analysis showed that oxidative stress (measured by F2-isoprostane) was higher in the morning than in the evening, but morning consumption of grape powder reduced this response. Similarly, an older animal study found that resveratrol acted as an antioxidant when given during the active period but had a pro-oxidant effect during the resting period. These findings suggest that grape polyphenols exert immunomodulatory effects depending on timing, with consumption during active periods—such as morning or daytime—potentially optimizing their benefits.

Beyond their time-dependent effects on oxidative stress and metabolism, grape polyphenols may also influence the body’s internal clock at a molecular level. An older study investigated whether proanthocyanidins modulate the expression of circadian clock genes in the liver, gut, and adipose tissue of healthy and obese rats. Rats were administered GSPE for 21 days at different doses. Researchers observed a dose-dependent overexpression of core clock genes (Per2 and Bmal1) in healthy animals. GSPEs also helped normalize disrupted clock gene expression in the liver and gut of obese rats, though their effects were less pronounced in adipose tissue. These findings suggest that dietary polyphenols, such as proanthocyanidins, may have a regulatory role in peripheral circadian clocks, potentially influencing metabolic health in both normal and obese states.

These findings highlight the connection between polyphenols, circadian rhythms, and overall health. Grape polyphenols not only support metabolic and immune function but also interact with the body’s internal clock, making it important to consume them at optimal times. When consumed in alignment with natural rhythms and seasonal patterns, polyphenols may be more bioavailable. Ultimately, when individuals are in harmony with nature, they may experience greater health benefits.

Best Ways to Consume Grapes

Grapes and grape products are high in polyphenols, but there may be more optimal times to consume them. Additionally, consuming certain grape products (i.e., alcoholic wine) may affect the circadian rhythm that regulates the sleep-wake cycle.

Ways to Get the Most Out of Grapes:

• Concord/purple grapes contain more polyphenols than red or green grapes, but all grapes can be enjoyed as sources of polyphenols.
• When possible, opt for organic grapes and grape products to increase polyphenols.
• Consuming grapes in shorter light periods (i.e., winter) may improve the bioavailability of their polyphenols.
• Enjoying a glass of organic red grape juice provides nearly as much phenolic content as some red wine varieties, making it a great non-alcoholic alternative with all the benefits.
• Eating grapes and grape products may benefit the body in different ways, depending on the timing of their consumption.

Final Word

Grapes are an excellent source of polyphenols, which have numerous health benefits, including effects on cardiovascular health, neurocognition, and even athletic muscle recovery from high-intensity exercise. Consuming grape products like juice, wine, raisins, and powders may also exert similar effects.

As always, talk to a doctor, nutritionist, or dietician before making any diet or lifestyle changes for personal options based on individual circumstances. Certain medications, including blood thinners, may be contraindicated with certain grape products.